FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kane, JM Strom, BL Eng, SM Faich, G Reynolds, RF D'Agostino, RB Ruskin, J Geier, J Karayal, ON Kremer, C AF Kane, John M. Strom, Brian L. Eng, Sybil M. Faich, Gerald Reynolds, Robert F. D'Agostino, Ralph B. Ruskin, Jeremy Geier, Jamie Karayal, Onur N. Kremer, Charlotte TI PRIMARY AND READJUDICATION MORTALITY RESULTS FROM ZODIAC, A LARGE SIMPLE TRIAL OF ZIPRASIDONE VS. OLANZAPINE IN PATIENTS WITH SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Kane, John M.] Zucker Hillside Hosp, Glen Oaks, NY USA. [Strom, Brian L.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Eng, Sybil M.; Reynolds, Robert F.; Geier, Jamie; Karayal, Onur N.; Kremer, Charlotte] Pfizer Inc, New York, NY USA. [Faich, Gerald] United BioSource Corp, Blue Bell, PA USA. [D'Agostino, Ralph B.] Boston Univ, Boston, MA 02215 USA. [Ruskin, Jeremy] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 183 EP 184 DI 10.1016/j.schres.2010.02.227 PG 2 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800228 ER PT J AU Strom, BL Eng, SM Faich, G Reynolds, RF D'Agostino, RB Ruskin, J Kane, JM Geier, J Karaya, ON Kremer, C AF Strom, Brian L. Eng, Sybil M. Faich, Gerald Reynolds, Robert F. D'Agostino, Ralph B. Ruskin, Jeremy Kane, John M. Geier, Jamie Karaya, Onur N. Kremer, Charlotte TI THE ZIPRASIDONE OBSERVATIONAL STUDY OF CARDIAC OUTCOMES (ZODIAC): FINDINGS FROM A LARGE SIMPLE TRIAL OF ZIPRASIDONE VS. OLANZAPINE IN REAL-WORLD USE AMONG 18154 PATIENTS WITH SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Strom, Brian L.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Eng, Sybil M.; Reynolds, Robert F.; Geier, Jamie; Karaya, Onur N.; Kremer, Charlotte] Pfizer Inc, New York, NY USA. [Faich, Gerald] United BioSource Corp, Blue Bell, PA USA. [D'Agostino, Ralph B.] Boston Univ, Boston, MA 02215 USA. [Ruskin, Jeremy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kane, John M.] Zucker Hillside Hosp, Glen Oaks, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 311 EP 311 DI 10.1016/j.schres.2010.02.523 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800525 ER PT J AU Nuechterlein, KH Green, MF Kern, RS AF Nuechterlein, Keith H. Green, Michael F. Kern, Robert S. TI RECENT ADVANCES IN TRANSLATING AND CULTURALLY ADAPTING THE MATRICS CONSENSUS COGNITIVE BATTERY FOR INTERNATIONAL USE SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Nuechterlein, Keith H.; Green, Michael F.; Kern, Robert S.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. [Green, Michael F.; Kern, Robert S.] VA Greater Angeles Healthcare Syst, MIRECC, VISN 22, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 329 EP 330 DI 10.1016/j.schres.2010.02.564 PG 2 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800566 ER PT J AU Ng, HP Kubicki, M Rathi, Y Malcolm, J Pelavin, P Kikinis, R Shenton, ME AF Ng, Hsiao Piau Kubicki, Marek Rathi, Yogesh Malcolm, James Pelavin, Paula Kikinis, Ron Shenton, Martha E. TI DECREASED FRACTIONAL ANISOTROPY IN INTER-HEMISPHERIC CONNECTION BETWEEN BILATERAL SUPERIOR TEMPORAL GYRUS GRAY MATTER IN CHRONIC SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Ng, Hsiao Piau; Kubicki, Marek; Rathi, Yogesh; Malcolm, James; Pelavin, Paula; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Ng, Hsiao Piau] Agcy Sci Technol & Res, Singapore Bioimaging Consortium, Singapore, Singapore. [Kubicki, Marek; Rathi, Yogesh; Shenton, Martha E.] Harvard Univ, VA Boston Healthcare Syst, Dept Psychiat, Clin Neurosci Div,Lab Neurosci,Sch Med, Brockton, MA 02401 USA. [Kikinis, Ron; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,MRI Div,Surg Planning Lab, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 342 EP 343 PG 2 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800598 ER PT J AU Milanovic, SM Thermenos, HW Brown, A Goldstein, JM Gabrieli, SW Makris, N Juelich, R Tsuang, MT Buka, SL Seidman, LJ AF Milanovic, Snezana M. Thermenos, Heidi W. Brown, Ariel Goldstein, Jill M. Gabrieli, Susan W. Makris, Nikos Juelich, Richard Tsuang, Ming T. Buka, Stephen L. Seidman, Larry J. TI MEDIAL PREFRONTAL CORTICAL ACTIVATION DURING WORKING MEMORY DIFFERENTIATES SCHIZOPHRENIA AND BIPOLAR PSYCHOTIC PATIENTS: A PILOT STUDY SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Milanovic, Snezana M.; Thermenos, Heidi W.; Goldstein, Jill M.; Juelich, Richard; Tsuang, Ming T.; Seidman, Larry J.] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Div Publ Psychiat,Dept Psychiat,Beth Israel Deaco, Boston, MA 02115 USA. [Milanovic, Snezana M.; Thermenos, Heidi W.; Goldstein, Jill M.; Makris, Nikos; Seidman, Larry J.] MGH HST Athinoula Martinos, Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Milanovic, Snezana M.; Brown, Ariel; Goldstein, Jill M.; Makris, Nikos; Tsuang, Ming T.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brown, Ariel; Seidman, Larry J.] MGH, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Goldstein, Jill M.] Harvard Univ, Sch Med, Dept Med, Div Womens Hlth,Connors Ctr Womens Hlth Gender Bi, Boston, MA 02115 USA. [Goldstein, Jill M.] Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA. [Gabrieli, Susan W.] MIT, Dept Brain & Cognit Sci, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02139 USA. [Makris, Nikos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr,Dept Neurol Services, Boston, MA 02129 USA. [Makris, Nikos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr,Dept Radiol Services, Boston, MA 02129 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Gen, La Jolla, CA 92093 USA. [Buka, Stephen L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 355 EP 355 DI 10.1016/j.schres.2010.02.623 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800625 ER PT J AU Genevsky, A Fisher, M Garrett, CT Cook, C Vinogradov, S AF Genevsky, Alexander Fisher, Melissa Garrett, Coleman T. Cook, Colleen Vinogradov, Sophia TI INCREASED SERUM BDNF INDUCED BY COGNITIVE TRAINING IN SCHIZOPHRENIA IS NEGATIVELY ASSOCIATED WITH BASELINE SAA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Genevsky, Alexander; Fisher, Melissa; Garrett, Coleman T.; Cook, Colleen; Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. [Genevsky, Alexander; Fisher, Melissa; Garrett, Coleman T.; Cook, Colleen; Vinogradov, Sophia] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 368 EP 368 DI 10.1016/j.schres.2010.02.653 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936801023 ER PT J AU Pietersen, CY Lim, MP Chen, J Stephens, R McCarley, RM Wool, TUW AF Pietersen, Charmaine Y. Lim, Maribel P. Chen, Jack Stephens, Robert McCarley, Robert M. Wool, Tsung-Ung W. TI MICROARRAY ANALYSIS OF PARVALBUMIN-CONTAINING INHIBITORY NEURONS IN THE SUPERIOR TEMPORAL GYRUS IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Pietersen, Charmaine Y.; Lim, Maribel P.; Wool, Tsung-Ung W.] McLean Hosp, Belmont, MA 02178 USA. [Chen, Jack; Stephens, Robert] SAIC Frederik, NCI, NIH, ABCC, Bethesda, MD USA. [Pietersen, Charmaine Y.; McCarley, Robert M.; Wool, Tsung-Ung W.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Pietersen, Charmaine Y.; McCarley, Robert M.; Wool, Tsung-Ung W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [McCarley, Robert M.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 371 EP 372 PG 2 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936801032 ER PT J AU Keefe, R Vinogradov, S Medalia, A Buckley, P Caroff, S D'Souza, D Harvey, P Graham, K Marder, S Miller, D Olson, S Patel, J Velligan, D Walker, T Haim, A Stroup, S AF Keefe, Richard Vinogradov, Sophia Medalia, Alice Buckley, Peter Caroff, Stanley D'Souza, Deepak Harvey, Phillip Graham, Karen Marder, Steve Miller, Del Olson, Steve Patel, Jayendra Velligan, Dawn Walker, Trina Haim, Adam Stroup, Scott TI FEASIBILITY STUDY OF MULTI-SITE COGNITIVE REMEDIATION IN THE SCHIZOPHRENIA TRIALS NETWORK (CRSTN) SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Keefe, Richard; Walker, Trina] Duke Univ, Med Ctr, Durham, NC USA. [Vinogradov, Sophia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Medalia, Alice; Stroup, Scott] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Buckley, Peter] Med Coll Georgia, Augusta, GA 30912 USA. [Caroff, Stanley] Univ Penn, Sch Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [D'Souza, Deepak] Yale Univ, Sch Med, New Haven, CT USA. [Harvey, Phillip] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Graham, Karen] Univ N Carolina, Chapel Hill, NC USA. [Marder, Steve] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Marder, Steve] VA Desert Pacific Mental Illness Res Educ & Clin, Los Angeles, CA USA. [Miller, Del] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Olson, Steve] Univ Minnesota, Minneapolis, MN USA. [Patel, Jayendra] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Velligan, Dawn] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Haim, Adam] NIMH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 394 EP 394 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936801081 ER PT J AU Wesnes, K Brooker, H Evins, AE AF Wesnes, Keith Brooker, Helen Evins, A. Eden TI A STUDY COMPARING THE MATRICS BATTERY WITH THE CDR SYSTEM IN SHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Wesnes, Keith; Brooker, Helen] United BioSource Corp, Goring on Thames, Oxon, England. [Wesnes, Keith] Swinburne Univ, Melbourne, Vic, Australia. [Evins, A. Eden] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 416 EP 416 DI 10.1016/j.schres.2010.02.1044 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936801132 ER PT J AU Schneiderman, JS Whitford, TJ Pelavin, PE Terry, DP Swisher, T Mesholam-Gately, RI Seidman, LJ Goldstein, JM McCarley, RW Kubicki, M Shenton, ME AF Schneiderman, Jason S. Whitford, Thomas J. Pelavin, Paula E. Terry, Douglas P. Swisher, Tali Mesholam-Gately, Raquelle I. Seidman, Larry J. Goldstein, Jill M. McCarley, Robert W. Kubicki, Marek Shenton, Martha E. TI DIFFUSION TENSOR IMAGING OF THE CINGULUM BUNDLE IN FIRST EPISODE SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Schneiderman, Jason S.; Whitford, Thomas J.; Pelavin, Paula E.; Terry, Douglas P.; Swisher, Tali; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Mesholam-Gately, Raquelle I.; Seidman, Larry J.; Goldstein, Jill M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [McCarley, Robert W.] VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 461 EP 461 DI 10.1016/j.schres.2010.02.862 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936801233 ER PT J AU Thermenos, HW Whitfield-Gabrieli, S Makris, N Brown, ALB Lee, E Giuliano, A Faraone, S Tsuang, MT Seidman, LJ AF Thermenos, Heidi W. Whitfield-Gabrieli, Susan Makris, Nikos Brown, Arid L. B. Lee, Erica Giuliano, Anthony Faraone, Stephen Tsuang, Ming T. Seidman, Larry J. TI ALTERED BRAIN FUNCTION DURING WORKING MEMORY IN ADOLESCENTS AND YOUNG ADULTS AT GENETIC RISK FOR BIPOLAR DISORDER: PRELIMINARY FINDINGS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Thermenos, Heidi W.; Lee, Erica; Giuliano, Anthony; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Harvard Med Sch, Boston, MA 02215 USA. [Thermenos, Heidi W.; Makris, Nikos; Brown, Arid L. B.; Seidman, Larry J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Faraone, Stephen] Upstate Med Univ, Med Genet Res Program, Syracuse, NY USA. [Tsuang, Ming T.] Univ Calif La Jolla, Dept Psychiat Ctr Behav Genom, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 473 EP 473 DI 10.1016/j.schres.2010.02.891 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936801262 ER PT J AU Lieberman, J AF Lieberman, Judy TI Master of the Cell SO SCIENTIST LA English DT Article ID FAS PROTECTS MICE; RNA; INTERFERENCE; INFECTION C1 [Lieberman, Judy] Childrens Hosp Boston, Immune Dis Inst, Boston, MA USA. [Lieberman, Judy] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. [Lieberman, Judy] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Lieberman, J (reprint author), Childrens Hosp Boston, Immune Dis Inst, Boston, MA USA. RI Lieberman, Judy/A-2717-2015 NR 7 TC 0 Z9 1 U1 0 U2 1 PU SCIENTIST INC PI PHILADELPHIA PA 400 MARKET ST, STE 1250, PHILADELPHIA, PA 19106 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD APR PY 2010 VL 24 IS 4 BP 42 EP 48 PG 7 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 574TX UT WOS:000276017700020 ER PT J AU Mayer, KH Mimiaga, MJ Safren, SA AF Mayer, Kenneth H. Mimiaga, Matthew J. Safren, Steven A. TI Out of the Closet and Into Public Health Focus: HIV and STDs in Men Who Have Sex With Men in Middle Income and Resource-Limited Countries SO SEXUALLY TRANSMITTED DISEASES LA English DT Editorial Material ID RISK-FACTORS; INFECTION; BEHAVIOR C1 [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Providence, RI 02906 USA. [Mayer, Kenneth H.] Brown Univ, Dept Med, Warren Alpert Sch Med, Providence, RI 02906 USA. [Mayer, Kenneth H.] Brown Univ, Dept Community Hlth, Warren Alpert Sch Med, Providence, RI 02906 USA. [Mimiaga, Matthew J.; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Fenway Inst, Boston, MA 02114 USA. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. RP Mayer, KH (reprint author), Brown Univ, Miriam Hosp, 164 Summit Ave, Providence, RI 02906 USA. EM kenneth_mayer@brown.edu NR 23 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD APR PY 2010 VL 37 IS 4 BP 205 EP 207 DI 10.1097/OLQ.0b013e3181d13d3e PG 3 WC Infectious Diseases SC Infectious Diseases GA 579MC UT WOS:000276373700001 PM 20145587 ER PT J AU Muessig, KE Tucker, JD Wang, BX Chen, XS AF Muessig, Kathryn E. Tucker, Joseph D. Wang, Bao-Xi Chen, Xiang-Sheng TI HIV and Syphilis Among Men Who Have Sex With Men in China: The Time to Act is Now SO SEXUALLY TRANSMITTED DISEASES LA English DT Editorial Material ID HEPATITIS-B; PREVALENCE; BEHAVIORS; SHANGHAI; INFECTIONS; HIV/AIDS; SPREAD; RISKS; WOMEN; CITY C1 [Chen, Xiang-Sheng] Chinese Acad Med Sci, Natl Ctr STD Control, China CDC, Nanjing 210042, Peoples R China. [Muessig, Kathryn E.; Wang, Bao-Xi; Chen, Xiang-Sheng] Peking Union Med Coll, Inst Dermatol, Nanjing, Peoples R China. [Muessig, Kathryn E.] Johns Hopkins Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Tucker, Joseph D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Chen, XS (reprint author), Chinese Acad Med Sci, Natl Ctr STD Control, China CDC, 12 Jiangwangmiao St, Nanjing 210042, Peoples R China. EM chenxs@ncstdlc.org FU FIC NIH HHS [K01 TW008200]; NIMH NIH HHS [F31 MH086345-01, F31 MH086345] NR 32 TC 7 Z9 7 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD APR PY 2010 VL 37 IS 4 BP 214 EP 216 DI 10.1097/OLQ.0b013e3181d13d2b PG 3 WC Infectious Diseases SC Infectious Diseases GA 579MC UT WOS:000276373700003 PM 20220563 ER PT J AU Brim, NM Venkatan, SK Gordon, JA Alexander, EK AF Brim, Nancy M. Venkatan, Suresh K. Gordon, James A. Alexander, Erik K. TI Long-Term Educational Impact of a Simulator Curriculum on Medical Student Education in an Internal Medicine Clerkship SO SIMULATION IN HEALTHCARE LA English DT Article DE Simulation; Medical student; Clinical reasoning ID HUMAN PATIENT SIMULATOR; CARDIOLOGY; RESPONSES; SKILLS AB Background: Medical simulation is frequently used in postgraduate medical training, but its value and sustainability in medical student education are less clear. We report the first long-term experience of mannequin simulation in an internal medicine clerkship. Methods: During a 6-year period (2002-2009), 327 Harvard medical students participated in a simulator-based teaching experience designed to expose students to the principles of myocardial infarction (MI). This experience was additive to a 12-week clerkship curriculum. Through blinded survey instruments, we sought to determine how the simulator exercise modified student exposure to a core curricular objective in the traditional clerkship. We also sought student and faculty perception of this educational tool and factors important to sustainability. Results: Three hundred twenty-seven consecutive students were exposed to the simulation exercise and their experiences evaluated. Three hundred twenty-six students (99%) described the simulation experience as valuable, with >69% requesting multiple sessions be provided during each clerkship. Although a core objective, only 78% of students reported having a didactic teaching session on MI during the clerkship, and only 47% of students reported exposure to a live patient with MI. Furthermore, only 15% of students reported exposure to at least two different clinical presentations of MI, allowing comparison and reflection. Thus, the simulation exercise provided the only exposure to this topic for 22% of students and facilitated comparisons of different clinical presentations for 85% of students. When students participated in both the simulator and the didactic sessions, 74% favored the simulation exercise. Faculty cited small group size, once monthly delivery and focused curricula as key points for sustainability of this effort. Conclusion: Mannequin simulation is a valuable and sustainable addition to a third-year internal medicine clerkship. For some students, simulation provides otherwise unavailable exposure to core content material. For the majority of students, simulation also provides the only means of exposure to multiple presentations of a single illness. Together, these data strongly suggest that simulation promotes both experiential learning and comparative analysis in a clerkship setting. (Sim Healthcare 5:75-81, 2010) C1 [Brim, Nancy M.; Alexander, Erik K.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Venkatan, Suresh K.; Gordon, James A.] Harvard Univ, Sch Med, GS Beckwith Gilbert & Katharine S Gilbert Med Edu, Boston, MA USA. [Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Alexander, EK (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St,PBB-B4, Boston, MA 02115 USA. EM ekalexander@partners.org NR 21 TC 7 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 J9 SIMUL HEALTHC JI Simul. Healthc. PD APR PY 2010 VL 5 IS 2 BP 75 EP 81 DI 10.1097/SIH.0b013e3181ca8edc PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 586UG UT WOS:000276938400002 PM 20389232 ER PT J AU Vazquez, J Rosenthal, DI AF Vazquez, Josue Rosenthal, Daniel I. TI Bilateral, symmetrical soft tissue calcifications in the face SO SKELETAL RADIOLOGY LA English DT Article DE Radiesse; Calcifications; Bisphosphonates; Soft tissue; CT; Face; Lipoatrophy; Cosmetic AB A 50-year-old woman with jaw pain and a history of bisphosphonate use was shown on radiography to have ill-defined soft tissue calcifications overlying the maxilla, mandible, and zygomatic bones bilaterally. The bones were normal. CT revealed similar findings. Although a broad imaging differential diagnosis was initially considered, further questioning of the patient revealed a history of facial injections with a calcium hydroxylapatite product for cosmetic purposes. The appearance of this increasingly popular treatment should be recognized to avoid errors in interpretation. C1 [Vazquez, Josue; Rosenthal, Daniel I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Vazquez, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Yawkey 6, Boston, MA 02114 USA. EM josuebmw3@gmail.com NR 5 TC 1 Z9 1 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 APR PY 2010 VL 39 IS 4 BP 387 EP 389 DI 10.1007/s00256-009-0853-0 PG 3 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 559US UT WOS:000274854100011 PM 20049592 ER PT J AU Richards, K Sawyer, AM AF Richards, Kathy Sawyer, Amy M. TI What We Don't Know about Sleep-Related Breathing Disorders in the Elderly SO SLEEP LA English DT Editorial Material ID WORKING-MEMORY; INTERMITTENT HYPOXIA; APNEA; BRAIN; CONSEQUENCES; IMPAIRMENT; ACTIVATION; DISEASE C1 [Richards, Kathy] Univ Penn, Sch Nursing, John A Hartford Ctr Geriatr Nursing Excellence, Philadelphia, PA 19104 USA. [Richards, Kathy] Univ Penn, Sch Nursing, Ctr Integrat Sci Aging, Philadelphia, PA 19104 USA. [Richards, Kathy] Madlyn & Leonard Abramson Ctr Jewish Life, Polisher Res Inst, N Wales, PA USA. [Sawyer, Amy M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Richards, K (reprint author), Univ Penn, Sch Nursing, John A Hartford Ctr Geriatr Nursing Excellence, Claire M Fagin Hall,418 Curie Blvd,Room 311, Philadelphia, PA 19104 USA. EM kathyr@nursing.upenn.edu FU NINR NIH HHS [K99 NR011173] NR 20 TC 1 Z9 1 U1 0 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 1 PY 2010 VL 33 IS 4 BP 423 EP 425 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 581IJ UT WOS:000276515500004 PM 20394310 ER PT J AU Brumberg, JS Nieto-Castanon, A Kennedy, PR Guenther, FH AF Brumberg, Jonathan S. Nieto-Castanon, Alfonso Kennedy, Philip R. Guenther, Frank H. TI Brain-computer interfaces for speech communication SO SPEECH COMMUNICATION LA English DT Article DE Brain-computer interface; Neural prosthesis; Speech restoration ID THOUGHT-TRANSLATION DEVICE; INTRACORTICAL ELECTRODE ARRAY; VISUAL-EVOKED POTENTIALS; NEURAL-NETWORK MODEL; CEREBRAL-CORTEX; CONE ELECTRODE; ELECTROCORTICOGRAPHIC SIGNALS; MICROELECTRODE ARRAYS; MACHINE INTERFACE; CORTICAL-NEURONS AB This paper briefly reviews current silent speech methodologies for normal and disabled individuals. Current techniques utilizing electromyographic (EMG) recordings of vocal tract movements are useful for physically healthy individuals but fail for tetraplegic individuals who do not have accurate voluntary control over the speech articulators. Alternative methods utilizing EMG from other body parts (e.g., hand, arm, or facial muscles) or electroencephalography (EEG) can provide capable silent communication to severely paralyzed users, though current interfaces are extremely slow relative to normal conversation rates and require constant attention to a computer screen that provides visual feedback and/or cueing. We present a novel approach to the problem of silent speech via an intracortical microelectrode brain-computer interface (BCI) to predict intended speech information directly from the activity of neurons involved in speech production. The predicted speech is synthesized and acoustically fed back to the user with a delay under 50 ms. We demonstrate that the Neurotrophic Electrode used in the BCI is capable of providing useful neural recordings for over 4 years, a necessary property for BCIs that need to remain viable over the lifespan of the user. Other design considerations include neural decoding techniques based on previous research involving BCIs for computer cursor or robotic arm control via prediction of intended movement kinematics from motor cortical signals in monkeys and humans. Initial results from a study of continuous speech production with instantaneous acoustic feedback show the BCI user was able to improve his control over an artificial speech synthesizer both within and across recording sessions. The success of this initial trial validates the potential of the intracortical microelectrode-based approach for providing a speech prosthesis that can allow much more rapid communication rates. (C) 2010 Elsevier By. All rights reserved. C1 [Brumberg, Jonathan S.; Guenther, Frank H.] Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. [Guenther, Frank H.] Boston Univ, Sargent Coll Hlth & Rehabil Sci, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA. [Guenther, Frank H.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Guenther, Frank H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Brumberg, Jonathan S.; Kennedy, Philip R.] Neural Signals Inc, Duluth, GA 30096 USA. [Nieto-Castanon, Alfonso] StatsANC LLC, Buenos Aires, DF, Argentina. RP Brumberg, JS (reprint author), Boston Univ, Dept Cognit & Neural Syst, 677 Beacon St, Boston, MA 02215 USA. EM brumberg@cns.bu.edu FU National Institute on Deafness and other Communication Disorders [R01 DC007683, R01 DC002852, R44 DC007050-02]; CELEST, an NSF Science of Learning Center [NSF SBE-0354378] FX This research was supported by the National Institute on Deafness and other Communication Disorders (R01 DC007683; R01 DC002852; R44 DC007050-02) and by CELEST, an NSF Science of Learning Center (NSF SBE-0354378). The authors thank the participant and his family for their dedication to this research project, Rob Law and Misha Panko for their assistance with the preparation of this manuscript and Tanja Schultz for her helpful comments. NR 76 TC 49 Z9 56 U1 1 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6393 EI 1872-7182 J9 SPEECH COMMUN JI Speech Commun. PD APR PY 2010 VL 52 IS 4 SI SI BP 367 EP 379 DI 10.1016/j.specom.2010.01.001 PG 13 WC Acoustics; Computer Science, Interdisciplinary Applications SC Acoustics; Computer Science GA 574XB UT WOS:000276026400009 PM 20204164 ER PT J AU Genevay, S Atlas, SJ Katz, JN AF Genevay, Stephane Atlas, Steve J. Katz, Jeffrey N. TI Variation in Eligibility Criteria From Studies of Radiculopathy due to a Herniated Disc and of Neurogenic Claudication due to Lumbar Spinal Stenosis A Structured Literature Review SO SPINE LA English DT Review DE radiculopathy; herniated disc; neurogenic claudication; lumbar spine stenosis; eligibility criteria ID RANDOMIZED CONTROLLED-TRIAL; LOW-BACK-PAIN; PLACEBO-CONTROLLED TRIAL; FOLLOW-UP; MICROENDOSCOPIC DISKECTOMY; NONOPERATIVE TREATMENT; CLINICAL-TRIAL; SCIATICA; THERAPY; EFFICACY AB Study Design. A structured literature review. Summary of the Background Data. Widely recognized classification criteria for rheumatologic disorders have resulted in well-defined patient populations for clinical investigation. Objective. We sought to determine whether similar criteria were needed for back pain disorders by examining variability in eligibility criteria in published studies. Methods. Studies involving radiculopathy due to lumbar herniated disc (HD) and for neurogenic claudication due to lumbar spinal stenosis (LSS) were identified. Randomized controlled trials published between January 1, 2006 and October 1, 2008 in select peer reviewed journals were retrieved, their eligibility criteria were identified and categorized. Results. Twelve eligible HD studies were identified. Thirteen unique categories of eligibility criteria were identified with a mean of 3.9 (+/-2.0) and a range from 0 to 8 categories per study. More categories were present for studies that included nonsurgical (5.6 +/- 2.5) treatment for studies with only surgical treatment (2.6 +/- 1.7) P = 0.04). Seven LSS studies met eligibility criteria, and 9 unique categories were identified. A mean of 5.0 (+/-2.2) categories with a range from 2 to 7 was used per study. Conclusion. Wide variation in the number and type of eligibility criteria from randomized clinical trials of well defined back pain syndromes was identified. These results support the need for developing and disseminating international classification criteria for these clinical conditions. C1 [Genevay, Stephane] Univ Hosp Geneva, Div Rheumatol, CH-1211 Geneva 14, Switzerland. [Genevay, Stephane; Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Genevay, Stephane; Katz, Jeffrey N.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Atlas, Steve J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Genevay, S (reprint author), Univ Hosp Geneva, Div Rheumatol, 26 Beau Sejour, CH-1211 Geneva 14, Switzerland. EM stephane.genevay@hcuge.ch OI Genevay, Stephane/0000-0003-4752-3186 FU NIH/NIAMS [P60 AR 47782, K24 02123, P60 AR048094] FX Supported by NIH/NIAMS P60 AR 47782 and NIH/NIAMS K24 02123 (to J.N.K.); and supported in part by a grant from (P60 AR048094) to the Multidisciplinary Clinical Research Center in Musculoskeletal Diseases from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (to S.J.A.). NR 40 TC 40 Z9 41 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 1 PY 2010 VL 35 IS 7 BP 803 EP 811 DI 10.1097/BRS.0b013e3181bc9454 PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 585NV UT WOS:000276833500014 PM 20228710 ER PT J AU Hingtgen, SD Kasmieh, R van de Water, J Weissleder, R Shah, K AF Hingtgen, Shawn D. Kasmieh, Randa van de Water, Jeroen Weissleder, Ralph Shah, Khalid TI A Novel Molecule Integrating Therapeutic and Diagnostic Activities Reveals Multiple Aspects of Stem Cell-Based Therapy SO STEM CELLS LA English DT Article DE TRAIL; Stem cells Cancer Imaging; Pharmacokinetics ID APOPTOSIS-INDUCING LIGAND; DELIVERED S-TRAIL; IN-VIVO; TUMOR-REGRESSION; FUSION PROTEINS; GLIOMA THERAPY; PRECURSOR; CANCER; GENE; PHARMACOKINETICS AB Stem cells are promising therapeutic delivery vehicles; however pre-clinical and clinical applications of stem cell-based therapy would benefit significantly from the ability to simultaneously determine therapeutic efficacy and pharmacokinetics of therapies delivered by engineered stem cells. In this study, we engineered and screened numerous fusion variants that contained therapeutic (TRAIL) and diagnostic (luciferase) domains designed to allow simultaneous investigation of multiple events in stem cell-based therapy in vivo. When various stem cell lines were engineered with the optimized molecule, SRLOL2TR, diagnostic imaging showed marked differences in the levels and duration of secretion between stem cell lines, while the therapeutic activity of the molecule showed the different secretion levels translated to significant variability in tumor cell killing. In vivo, simultaneous diagnostic and therapeutic monitoring revealed that stem cell-based delivery significantly improved pharmacokinetics and anti-tumor effectiveness of the therapy compared to intravenous or intratumoral delivery. As treatment for highly malignant brain tumor xenografts, tracking SRLOL2TR showed stable stem cell-mediated delivery significantly regressed peripheral and intracranial tumors. Together, the integrated diagnostic and therapeutic properties of SRLOL2TR answer critical questions necessary for successful utilization of stem cells as novel therapeutic vehicles. STEM CELLS 2010;28:832-841 C1 [Hingtgen, Shawn D.; Kasmieh, Randa; van de Water, Jeroen; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA. [Hingtgen, Shawn D.; Kasmieh, Randa; van de Water, Jeroen; Shah, Khalid] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Ctr Syst Biol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shah, Khalid] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 149 13th St, Charlestown, MA 02129 USA. EM kshah@helix.mgh.harvard.edu RI van de Water, Jeroen/F-1302-2011 OI van de Water, Jeroen/0000-0001-6974-2270 FU American Brain Tumor Association; American Cancer Gene Therapy; American Cancer Society; [R21 CA131980] FX This work was supported by the American Brain Tumor Association (K. S., S. H.), American Cancer Gene Therapy (K. S.), and American Cancer Society (K. S.), and R21 CA131980 (K. S.) NR 31 TC 21 Z9 21 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD APR PY 2010 VL 28 IS 4 BP 832 EP 841 DI 10.1002/stem.313 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 588SY UT WOS:000277095400021 PM 20127797 ER PT J AU Mandava, P Kalkonde, YV Rochat, RH Kent, TA AF Mandava, Pitchaiah Kalkonde, Yogeshwar V. Rochat, Ryan H. Kent, Thomas A. TI A Matching Algorithm to Address Imbalances in Study Populations Application to the National Institute of Neurological Diseases and Stroke Recombinant Tissue Plasminogen Activator Acute Stroke Trial SO STROKE LA English DT Article DE acute treatment; acute stroke; cerebrovascular accident; matching; nearest neighbor ID ACUTE ISCHEMIC-STROKE; NINDS; REANALYSIS; SCORE AB Background and Purpose-Outcome from stroke is highly dependent on baseline conditions. Patients with stroke have a wide range of severities, ages, and etiologies and it has proven difficult to achieve randomization of key variables in clinical trials. We present a new post hoc approach to achieve balance among selected variables. To illustrate the approach, we rebalanced the National Institute of Neurological Diseases and Stroke Recombinant Tissue Plasminogen Activator trial, in which the contribution of baseline imbalances continues to be debated. Methods-We selected baseline stroke severity (National Institutes of Health Stroke Scale), age, and glucose as matching criteria. The closest matched placebo and treated subjects were identified based on nearness to each other in 3-dimensional Euclidean space. Matching was performed within the quintiles of National Institutes of Health Stroke Scale that have been previously used to assess balance. Subjects who could not be matched were eliminated. Outcomes were assessed using the original specified National Institute of Neurological Diseases and Stroke trial measures. Results-We successfully matched the 2 arms resulting in nearly identical baseline characteristics and distribution among quintiles. Despite fewer subjects after outlier elimination, the primary outcome measures remained significantly improved. After rebalancing, the magnitude of benefit was reduced by 13% to 23%. Benefit was apparent mostly in the large vessel occlusion subtype. Conclusion-This study demonstrated the feasibility of rebalancing individual subjects within a randomized trial. After rebalancing and outlier elimination, recombinant tissue plasminogen activator continued to demonstrate improved outcome. That the apparent treatment effect was reduced suggests that imbalances contributed to the magnitude of the original National Institute of Neurological Diseases and Stroke outcomes. This method could in theory be applied to any data set to find matched subjects for outcome or other analyses. (Stroke. 2010; 41: 765-770.) C1 [Mandava, Pitchaiah] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, VA Med Ctr, Stroke Program, Houston, TX 77030 USA. RP Mandava, P (reprint author), Baylor Coll Med, Dept Neurol, 2002 Holcombe Blvd 127, Houston, TX 77030 USA. EM pmandava@bcm.tmc.edu RI Mandava, Pitchaiah/B-6046-2013; OI Mandava, Pitchaiah/0000-0003-4957-4518; Kent, Thomas/0000-0002-9877-7584 NR 28 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP 765 EP 770 DI 10.1161/STROKEAHA.109.574103 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100038 PM 20167911 ER PT J AU Almandoz, JED Su, HS Schaefer, PW Pomerantz, SR Lev, MH Gonzalez, RG Romero, JM AF Almandoz, Josser E. Delgado Su, Henry S. Schaefer, Pamela W. Pomerantz, Stuart R. Lev, Michael H. Gonzalez, R. Gilberto Romero, Javier M. TI Frequency of Adequate Contrast Opacification of the Dural Venous Sinuses With CT Angiography in the Setting of Intracerebral Hemorrhage: Comparison of 16 and 64-Slice CT Angiography Techniques SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Almandoz, Josser E. Delgado] Massachusetts Gen Hosp, Edward Mallinckrodt Inst Radiol, Boston, MA 02114 USA. [Almandoz, Josser E. Delgado] Massachusetts Gen Hosp, Edward Mallinckrodt Inst Radiol, St Louis, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E312 EP E313 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100477 ER PT J AU Almandoz, JED Kelly, HR Brouwers, HB Yoo, AJ Stone, MJ Schaefer, PW Goldstein, JN Rosand, J Lev, MH Gonzalez, RG Romero, JM AF Almandoz, Josser E. Delgado Kelly, Hillary R. Brouwers, H. Bart Yoo, Albert J. Stone, Michael J. Schaefer, Pamela W. Goldstein, Joshua N. Rosand, Jonathan Lev, Michael H. Gonzalez, R. Gilberto Romero, Javier M. TI Frequency and Predictive Value of the CT Angiography Spot Sign in Secondary ICH SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Almandoz, Josser E. Delgado] Massachusetts Gen Hosp, Mallinckrodt Inst Radiol, Boston, MA 02114 USA. RI Goldstein, Joshua/H-8953-2016 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E310 EP E311 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100471 ER PT J AU Almandoz, JED Schaefer, PW Goldstein, JN Rosand, J Lev, MH Gonzalez, RG Romero, JM AF Almandoz, Josser E. Delgado Schaefer, Pamela W. Goldstein, Joshua N. Rosand, Jonathan Lev, Michael H. Gonzalez, R. Gilberto Romero, Javier M. TI Practical Risk Stratification for the Presence of Underlying Vascular Lesions in Patients With Intracerebral Hemorrhage: The Secondary ICH Score SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Almandoz, Josser E. Delgado] Massachusetts Gen Hosp, Mallinckrodt Inst Radiol, Boston, MA 02114 USA. [Almandoz, Josser E. Delgado] Massachusetts Gen Hosp, Mallinckrodt Inst Radiol, St Louis, MA USA. RI Goldstein, Joshua/H-8953-2016 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E211 EP E211 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100104 ER PT J AU Arsava, EM Gokcay, F Baykaner, T Garg, P Wu, O Singhal, AB Furie, KL Sorensen, AG Ay, H AF Arsava, Ethem Murat Gokcay, Figen Baykaner, Tuna Garg, Priya Wu, Ona Singhal, Aneesh B. Furie, Karen L. Sorensen, A. Gregory Ay, Hakan TI Conversion of Ischemic but Viable Tissue Into Infarction is Different Between Men and Women SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Arsava, Ethem Murat; Gokcay, Figen; Baykaner, Tuna; Garg, Priya; Wu, Ona; Sorensen, A. Gregory; Ay, Hakan] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Cntr Biomed Imaging, Boston, MA 02114 USA. [Singhal, Aneesh B.; Furie, Karen L.; Ay, Hakan] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E274 EP E274 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100333 ER PT J AU Ay, H Arsava, EM Furie, KL Schwamm, LH Sorensen, AG AF Ay, Hakan Arsava, Ethem Murat Furie, Karen L. Schwamm, Lee H. Sorensen, A. Gregory TI Prediction of Subsequent Stroke Risk in TIA Patients With Brain Infarction SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Ay, Hakan; Furie, Karen L.; Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Ay, Hakan; Arsava, Ethem Murat; Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Cntr Biomed Imaging, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E241 EP E241 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100212 ER PT J AU Batista, LM Lima, FO Januzzi, JL Donahue, V Snydeman, C Greer, DM AF Batista, Leonardo M. Lima, Fabricio O. Januzzi, James L., Jr. Donahue, Vivian Snydeman, Colleen Greer, David M. TI Combined Cardiac Catheterization and Therapeutic Hypothermia Following Cardiac Arrest is Feasible and Safe SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Batista, Leonardo M.; Lima, Fabricio O.; Januzzi, James L., Jr.; Donahue, Vivian; Snydeman, Colleen; Greer, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E260 EP E260 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100276 ER PT J AU Biffi, A Halpin, A Towfighi, A Gilson, A Busl, K Rost, NS Smith, EE Greenberg, SM Rosand, J Viswanathan, A AF Biffi, Alessandro Halpin, Amy Towfighi, Amytis Gilson, Aaron Busl, Katharina Rost, Natalia S. Smith, Eric E. Greenberg, Steven M. Rosand, Jonathan Viswanathan, Anand TI Antiplatelet Agents, Cerebral Amyloid Angiopathy and Recurrent Intracerebral Hemorrhage SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Biffi, Alessandro; Halpin, Amy; Gilson, Aaron; Busl, Katharina; Rost, Natalia S.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Towfighi, Amytis] Univ So Calif, Los Angeles, CA USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E378 EP E378 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100730 ER PT J AU Cheng-Ching, E Levy, EI Zaidat, O Natarajan, SK Kalia, JS Jovin, TG Yoo, AJ Nogueira, RG Rymer, M Tayal, AH Hsu, DP Liebeskind, DS Abou-Chebl, A Nanda, A Tian, M Hao, Q Nguyen, TN Chen, M Gupta, R AF Cheng-Ching, Esteban Levy, Elad I. Zaidat, Osama Natarajan, Sabareesh K. Kalia, Junaid S. Jovin, Tudor G. Yoo, Albert J. Nogueira, Raul G. Rymer, Marilyn Tayal, Ashis H. Hsu, Daniel P. Liebeskind, David S. Abou-Chebl, Alex Nanda, Ashish Tian, Melissa Hao, Qing Nguyen, Thanh N. Chen, Michael Gupta, Rishi CA UCLA Revascularization Investigato TI Intracranial Stenting is Associated With Higher Rates of Vessel Recanalization During Endovascular Therapy for Acute Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Gupta, Rishi] Cleveland Clin Fdn, Cerebrovasc Ctr, Cleveland, OH 44195 USA. [Levy, Elad I.; Natarajan, Sabareesh K.] SUNY Buffalo, Buffalo, NY 14260 USA. [Zaidat, Osama; Kalia, Junaid S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Jovin, Tudor G.] Univ Pittsburgh, Med Ctr, Stroke Inst, Pittsburgh, PA USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rymer, Marilyn] St Lukes Brain & Stroke Inst, Kansas City, MO USA. [Tayal, Ashis H.; Tian, Melissa] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Hsu, Daniel P.; Nanda, Ashish] Univ Hosp, Cleveland, OH USA. [Liebeskind, David S.; Hao, Qing; UCLA Revascularization Investigato] Univ Calif Los Angeles, Los Angeles, CA USA. [Abou-Chebl, Alex] Univ Louisville, Med Ctr, Louisville, KY 40292 USA. [Nguyen, Thanh N.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Chen, Michael] Rush Univ, Med Ctr, Chicago, IL 60612 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E228 EP E228 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100161 ER PT J AU Choi, JH Neimark, MA Konstas, AA Lee, LK Chiang, YT Marshall, RS Pile-Spellman, J AF Choi, Jae H. Neimark, Matthew A. Konstas, Angelos A. Lee, Leslie K. Chiang, Yi T. Marshall, Randolph S. Pile-Spellman, John TI Brain and Systemic Temperature Changes During Selective Endovascular Brain Cooling With Cold Saline: A Translational Research Project SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Choi, Jae H.; Neimark, Matthew A.; Lee, Leslie K.; Chiang, Yi T.; Marshall, Randolph S.; Pile-Spellman, John] Columbia Univ, Med Ctr, New York, NY USA. [Konstas, Angelos A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E373 EP E373 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100714 ER PT J AU Corbin, ZA Rost, NS Parides, MK Blumberg, JB Milbury, PE Arai, K Hartdegen, SN Lo, EH Feske, SK Furie, KL AF Corbin, Zachary A. Rost, Natalia S. Parides, Michael K. Blumberg, Jeffrey B. Milbury, Paul E. Arai, Ken Hartdegen, Sophia N. Lo, Eng H. Feske, Steven K. Furie, Karen L. TI White Matter Hyperintensity Volume Correlates With Levels of Matrix Metalloproteinase-2 SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Corbin, Zachary A.; Rost, Natalia S.; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parides, Michael K.] Mt Sinai Sch Med, New York, NY USA. [Blumberg, Jeffrey B.; Milbury, Paul E.] Tufts Univ, Boston, MA 02111 USA. [Arai, Ken; Hartdegen, Sophia N.; Lo, Eng H.] Massachusetts Gen Hosp, Charlestown, MA USA. [Feske, Steven K.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E370 EP E370 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100700 ER PT J AU Dierksen, GA Skehan, ME Khan, MA Becker, JA Betensky, RA Frosch, MP Rosand, J Viswanathan, A Johnson, K Salat, DH Greenberg, SM AF Dierksen, Gregory A. Skehan, Maureen E. Khan, Muhammad A. Becker, John A. Betensky, Rebecca A. Frosch, Matthew P. Rosand, Jonathan Viswanathan, Anand Johnson, Keith Salat, David H. Greenberg, Steven M. TI Spatial Association Between Cerebral Microbleeds and beta-Amyloid Deposition in Cerebral Amyloid Angiopathy SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Dierksen, Gregory A.; Skehan, Maureen E.; Khan, Muhammad A.; Rosand, Jonathan; Viswanathan, Anand; Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Becker, John A.; Johnson, Keith; Salat, David H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E342 EP E342 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100589 ER PT J AU Fan, X Yu, ZY Dai, HB Lok, JM Singhal, AB Van Cott, EM Lo, EH Wang, XY AF Fan, Xiang Yu, Zhanyang Dai, Haibin Lok, Josephine M. Singhal, Aneesh B. Van Cott, Elizabeth M. Lo, Eng H. Wang, Xiaoying TI Impaired Reperfusion and Worse Neurological Outcomes in a Focal Embolic Stroke Model of Diabetic Rats After tPA Thrombolytic Therapy SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Fan, Xiang; Yu, Zhanyang; Dai, Haibin; Lok, Josephine M.; Singhal, Aneesh B.; Van Cott, Elizabeth M.; Lo, Eng H.; Wang, Xiaoying] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E349 EP E349 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100617 ER PT J AU Greenberg, CH Frosch, MP Greenberg, SM AF Greenberg, Charles H. Frosch, Matthew P. Greenberg, Steven M. TI Modeling the Growth of Microbleeds Into Macrobleeds SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Greenberg, Charles H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Frosch, Matthew P.; Greenberg, Steven M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Frosch, Matthew P.; Greenberg, Steven M.] Harvard Univ, Sch Med, Boston, MA 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E376 EP E377 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100725 ER PT J AU Gupta, R Jovin, TG Levy, EI Yoo, AJ Rymer, MM Tayal, AH Hsu, DP Liebeskind, DS Natarajan, SK Nogueira, RG Nanda, A Tian, M Zaidat, O Hao, Q Kalia, JS Nguyen, TN Chen, M Abou-Chebl, A AF Gupta, Rishi Jovin, Tudor G. Levy, Elad I. Yoo, Albert J. Rymer, Marilyn M. Tayal, Ashis H. Hsu, Daniel P. Liebeskind, David S. Natarajan, Sabareesh K. Nogueira, Raul G. Nanda, Ashish Tian, Melissa Zaidat, Osama Hao, Qing Kalia, Junaid S. Nguyen, Thanh N. Chen, Michael Abou-Chebl, Alex CA UCLA Revascularization Investigato TI General Anesthesia During Endovascular Therapy for Acute Stroke Intervention is Associated With Increased Mortality and Worse Clinical Outcomes SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Gupta, Rishi] Cleveland Clin Fdn, Cerebrovasc Ctr, Cleveland, OH 44195 USA. [Jovin, Tudor G.] Univ Pittsburgh, Med Ctr, Stroke Inst, Pittsburgh, PA USA. [Levy, Elad I.; Natarajan, Sabareesh K.] SUNY Buffalo, Buffalo, NY 14260 USA. [Yoo, Albert J.; Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rymer, Marilyn M.] St Lukes Brain & Stroke Inst, Kansas City, MO USA. [Tayal, Ashis H.; Tian, Melissa] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Hsu, Daniel P.; Nanda, Ashish] Univ Hosp, Cleveland, OH USA. [Liebeskind, David S.; Hao, Qing; UCLA Revascularization Investigato] Univ Calif Los Angeles, Los Angeles, CA USA. [Zaidat, Osama; Kalia, Junaid S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Nguyen, Thanh N.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Chen, Michael] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Abou-Chebl, Alex] Univ Louisville, Med Ctr, Louisville, KY 40292 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E228 EP E228 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100162 ER PT J AU Gurol, ME Davis, PH Leira, EC Strader, S Adams, HP AF Gurol, Mahmut E. Davis, Patricia H. Leira, Enrique C. Strader, Scott Adams, Harold P., Jr. TI The Extent of White Matter Disease on Acute Magnetic Resonance Imaging is an Independent Predictor of Outcome in Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Gurol, Mahmut E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Davis, Patricia H.; Leira, Enrique C.; Strader, Scott; Adams, Harold P., Jr.] Univ Iowa, Iowa City, IA 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E297 EP E298 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100418 ER PT J AU Hu, RL Yoo, A Hakimelahi, R Lev, M Nogueira, R Hirsch, J Gonzalez, RG Schaefer, P AF Hu, Ranliang Yoo, Albert Hakimelahi, Reza Lev, Michael Nogueira, Raul Hirsch, Joshua Gonzalez, Ramon G. Schaefer, Pamela TI CTA Source Images in the Era of Fast, Volume CT Scanning: Are They Still "DWI" Weighted? SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Hu, Ranliang; Yoo, Albert; Hakimelahi, Reza; Lev, Michael; Nogueira, Raul; Hirsch, Joshua; Gonzalez, Ramon G.; Schaefer, Pamela] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E238 EP E238 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100201 ER PT J AU Kalia, JS Batista, LM Rayes, M Etezadi, V Sweeney, J Pryor, JC Nogueira, RG Xavier, AR Gupta, R Linfante, I Norbash, A Nguyen, T Edgell, R Lynch, JR Fitzsimmons, BF Zaidat, OO AF Kalia, Junaid S. Batista, Leonardo M. Rayes, Mahmoud Etezadi, Vahid Sweeney, Justin Pryor, Johnny C. Nogueira, Raul G. Xavier, Andrew R. Gupta, Rishi Linfante, Italo Norbash, Alexander Nguyen, Thanh Edgell, Randy Lynch, John R. Fitzsimmons, Brian-Fred Zaidat, Osama O. CA Endovasc Coiling Small Aneurysm Mu TI Safety and Feasibility of Elective Endovascular Coiling of Very Small (2-7 mm) Unruptured Cerebral Aneurysms (ECOSA Study): A Multicenter Experience Analysis SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Kalia, Junaid S.; Lynch, John R.; Fitzsimmons, Brian-Fred; Zaidat, Osama O.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Batista, Leonardo M.; Pryor, Johnny C.; Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rayes, Mahmoud; Xavier, Andrew R.] Wayne State Univ, Detroit, MI USA. [Etezadi, Vahid; Linfante, Italo] Baptist Cardiac & Vasc Inst, Miami, FL USA. [Sweeney, Justin; Edgell, Randy] St Louis Univ, St Louis, MO 63103 USA. [Gupta, Rishi] Cleveland Clin, Cleveland, OH 44106 USA. [Norbash, Alexander; Nguyen, Thanh] Boston Univ, Sch Med, Boston, MA 02118 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E242 EP E242 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100216 ER PT J AU Kelly, HR Almandoz, JED Passanese, JC Lev, MH Schaefer, PW Gonzalez, RG Romero, JM AF Kelly, Hillary R. Almandoz, Josser E. Delgado Passanese, John C. Lev, Michael H. Schaefer, Pamela W. Gonzalez, R. G. Romero, Javier M. TI The CT Angiography Spot Sign Predicts Hematoma Expansion and In-hospital Mortality in Traumatic Subdural Hemorrhage SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Almandoz, Josser E. Delgado] Massachusetts Gen Hosp, Mallinckrodt Inst Radiol, Boston, MA 02114 USA. [Passanese, John C.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E311 EP E312 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100474 ER PT J AU Kemmling, A Pervez, MA Lev, MH Masrur, S Payabvash, S Schwamm, LH AF Kemmling, Andre Pervez, Muhammad A. Lev, Michael H. Masrur, Shibab Payabvash, Seyedmehdi Schwamm, Lee H. TI Hospital Acquired Pneumonia is Linked to Peri-insular Right Hemispheric and Infratentorial Acute Stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Kemmling, Andre] Univ Munster, Munster, Germany. [Pervez, Muhammad A.; Lev, Michael H.; Masrur, Shibab; Payabvash, Seyedmehdi; Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E380 EP E380 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100741 ER PT J AU Lima, FO Silva, GS Batista, LM Camargo, EC Singhal, AB Ay, H Greer, DM Yoo, AJ Lev, MH Harris, GJ Koroshetz, WJ Smith, WS Furie, KL Nogueira, RG AF Lima, Fabricio O. Silva, Gisele S. Batista, Leonardo M. Camargo, Erica C. Singhal, Aneesh B. Ay, Hakan Greer, David M. Yoo, Albert J. Lev, Michael H. Harris, Gordon J. Koroshetz, Walter J. Smith, Wade S. Furie, Karen L. Nogueira, Raul G. TI Natural History of Untreated Strokes Due to Proximal Anterior Circulation Occlusions Detected on CT Angiography SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Lima, Fabricio O.; Silva, Gisele S.; Batista, Leonardo M.; Camargo, Erica C.; Singhal, Aneesh B.; Ay, Hakan; Greer, David M.; Yoo, Albert J.; Lev, Michael H.; Harris, Gordon J.; Furie, Karen L.; Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koroshetz, Walter J.] NINDS, NIH, Bethesda, MD 20892 USA. [Smith, Wade S.] UCSF Med Ctr, San Francisco, CA USA. RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E333 EP E333 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100559 ER PT J AU Lima, FO Silva, GS Levy, MH Harris, G Smith, WS Halpern, EF Koroshetz, W Furie, KL AF Lima, Fabricio O. Silva, Gisele S. Levy, Michael H. Harris, Gordon Smith, Wade S. Halpern, Elkan F. Koroshetz, Walter Furie, Karen L. TI Differences in Risk Factors Between Intracranial and Extracranial Atherosclerosis in a Predominantly White American Population SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Lima, Fabricio O.; Silva, Gisele S.; Levy, Michael H.; Harris, Gordon; Halpern, Elkan F.; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Wade S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Koroshetz, Walter] NINDS, Bethesda, MD 20892 USA. RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E271 EP E271 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100320 ER PT J AU Liu, J Gao, BB Clermont, A Chilcote, T Sinha, S Feener, E AF Liu, Jia Gao, Ben-Bo Clermont, Allen Chilcote, Tamie Sinha, Sukanto Feener, Edward TI Activated Plasma Kallikrein Impairs Hemostasis and Contributes to Cerebral Hemorrhage in Hyperglycemia SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Liu, Jia; Gao, Ben-Bo; Clermont, Allen; Feener, Edward] Joslin Diabet Ctr, Boston, MA 02215 USA. [Chilcote, Tamie; Sinha, Sukanto] ActiveSite Pharmaceut Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E377 EP E377 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100726 ER PT J AU Natarajan, SK Ogilvy, CS Hopkins, LN Siddiqui, AH Levy, EI AF Natarajan, Sabareesh K. Ogilvy, Christopher S. Hopkins, Leo N. Siddiqui, Adnan H. Levy, Elad I. TI Initial Experience With a Second-generation Everolimus-eluting Stent for Treatment of Intracranial Atherosclerosis SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Natarajan, Sabareesh K.; Hopkins, Leo N.; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Buffalo, NY 14260 USA. [Ogilvy, Christopher S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E314 EP E314 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100482 ER PT J AU Nguyen, TN Zaidat, OO Gupta, R Nogueira, RG Tariq, N Kalia, JS Norbash, AM Qureshi, AI AF Nguyen, Thanh N. Zaidat, Osama O. Gupta, Rishi Nogueira, Raul G. Tariq, Nauman Kalia, Junaid S. Norbash, Alexander M. Qureshi, Adnan I. TI Balloon Angioplasty for Intracranial Atherosclerotic Disease Using New Generation Angioplasty Balloon Catheters: Periprocedural Risks and Short Term Outcomes in a Multicenter Study SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Nguyen, Thanh N.; Norbash, Alexander M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Zaidat, Osama O.; Kalia, Junaid S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gupta, Rishi] Cleveland Clin, Cerebrovasc Cntr, Cleveland, OH 44106 USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tariq, Nauman; Qureshi, Adnan I.] Univ Minnesota, Zeenat Qureshi Stroke Rsch Cntr, Minneapolis, MN 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E355 EP E355 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100639 ER PT J AU Nogueira, RG Gupta, R Liebeskind, DS Rymer, MM Barreto, AD Levy, EI Zaidat, OO Rai, A Baxter, B Jovin, T AF Nogueira, Raul G. Gupta, Rishi Liebeskind, David S. Rymer, Marilyn M. Barreto, Andrew D. Levy, Elad I. Zaidat, Osama O. Rai, Ansaar Baxter, Blaise Jovin, Tudor TI Neither Time to Treatment Nor the Use of Adjunctive Intra-arterial Thrombolytics Increase the Risk for Symptomatic Intracranial Hemorrhage After Endovascular Treatment of CT Perfusion or MRI-selected Stroke Patients Treated at Late Time Windows: Analysis of the Pre-DAWN Dataset SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gupta, Rishi] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Liebeskind, David S.] UCLA Revascularizat Investigators, Los Angeles, CA USA. [Rymer, Marilyn M.] St Lukes Brain & Stroke Inst, Kansas City, MO USA. [Barreto, Andrew D.] Univ Texas Houston Med Sch, Houston, TX USA. [Levy, Elad I.] SUNY Buffalo, Buffalo, NY 14260 USA. [Zaidat, Osama O.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Rai, Ansaar] W Virginia Univ, Morgantown, VA USA. [Baxter, Blaise] Erlanger Reg Stroke Ctr, Chattanooga, TN USA. [Jovin, Tudor] UPMC, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E227 EP E227 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100159 ER PT J AU Nogueira, RG Smith, WS Jovin, T Liebeskind, DS Budzik, RF Baxter, B Rymer, MM AF Nogueira, Raul G. Smith, Wade S. Jovin, Tudor Liebeskind, David S. Budzik, Ronald F. Baxter, Blaise Rymer, Marilyn M. TI Thrombectomy for Acute Ischemic Stroke Patients Aged 80 Years or Older: Long-term Outcomes in 178 Patients SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Wade S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Jovin, Tudor] UPMC, Pittsburgh, PA USA. [Liebeskind, David S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Budzik, Ronald F.] Riverside Methodist Hosp, Columbus, OH 43214 USA. [Baxter, Blaise] Erlanger Med Ctr, Chattanooga, TN USA. [Rymer, Marilyn M.] St Lukes Hosp, Kansas City, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E227 EP E228 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100160 ER PT J AU Oleinik, A Romero, J Almandoz, JED Schwab, K Hillary, RK Greenberg, SM Rosand, J Goldstein, JN AF Oleinik, Alexandra Romero, Javier Almandoz, Josser E. Delgado Schwab, Kristin Hillary, R. K. Greenberg, Steven M. Rosand, Jonathan Goldstein, Joshua N. TI Patients With Hematoma Expansion Following Acute Intracerebral Hemorrhage Often Present Late or With an Unknown Onset Time SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Oleinik, Alexandra; Romero, Javier; Schwab, Kristin; Hillary, R. K.; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Almandoz, Josser E. Delgado] Washington Univ, St Louis Sch Med, St Louis, MO USA. RI Goldstein, Joshua/H-8953-2016 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E313 EP E313 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100479 ER PT J AU Pervez, MA Rymer, M Lainhart, K Masrur, S Jauch, EC Schwamm, LH AF Pervez, Muhammad A. Rymer, Marilyn Lainhart, Kathy Masrur, Shihab Jauch, Edward C. Schwamm, Lee H. TI EMS Treatment and Transport of Stroke Patients Post IV tPA: Baseline Adherence to Recommended Processes of Care for "Drip and Ship" Patients SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Pervez, Muhammad A.; Masrur, Shihab; Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rymer, Marilyn; Lainhart, Kathy] St Lukes Hosp, Kansas City, MO USA. [Jauch, Edward C.] Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E287 EP E288 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100380 ER PT J AU Pikula, A Beiser, AS Himali, JJ Debette, S DeCarli, C Au, R Selhub, J Tofler, GH Wang, TJ Kelly-Hayes, M Kase, CS Benjamin, EJ Vasan, RS Wolf, PA Seshadri, S AF Pikula, Aleksandra Beiser, Alexa S. Himali, Jayandra J. Debette, Stephanie DeCarli, Charles Au, Rhoda Selhub, Jacob Tofler, Geoffrey H. Wang, Thomas J. Kelly-Hayes, Margaret Kase, Carlos S. Benjamin, Emelia J. Vasan, Ramachandran S. Wolf, Philip A. Seshadri, Sudha TI Multiple Biomarkers and Risk of Clinical and Subclinical Vascular Brain Injury: The Framingham Offspring Study SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Pikula, Aleksandra; Beiser, Alexa S.; Himali, Jayandra J.; Debette, Stephanie; Au, Rhoda; Kelly-Hayes, Margaret; Kase, Carlos S.; Benjamin, Emelia J.; Vasan, Ramachandran S.; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med & Publ Hlth, Boston, MA 02215 USA. [Pikula, Aleksandra; Beiser, Alexa S.; Himali, Jayandra J.; Debette, Stephanie; Au, Rhoda; Kelly-Hayes, Margaret; Kase, Carlos S.; Benjamin, Emelia J.; Vasan, Ramachandran S.; Wolf, Philip A.; Seshadri, Sudha] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Pikula, Aleksandra; Beiser, Alexa S.; Himali, Jayandra J.; Debette, Stephanie; Au, Rhoda; Kelly-Hayes, Margaret; Kase, Carlos S.; Benjamin, Emelia J.; Vasan, Ramachandran S.; Wolf, Philip A.; Seshadri, Sudha] Framingham Heart Dis Epidemiol Study, Boston, MA USA. [DeCarli, Charles] Univ Calif Davis, Sacramento, CA 95817 USA. [Selhub, Jacob] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA. [Tofler, Geoffrey H.] Royal N Shore Hosp, Sydney, NSW, Australia. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI DeCarli, Charles/B-5541-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E240 EP E240 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100209 ER PT J AU Poisson, SN Nguyen-Huynh, MN Johnston, SC Furie, KL Lev, MH Smith, WS AF Poisson, Sharon N. Nguyen-Huynh, Mai N. Johnston, S. Claiborne Furie, Karen L. Lev, Michael H. Smith, Wade S. TI Large Vessel Occlusion Does Not Predict Outcome in TIA SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Poisson, Sharon N.; Nguyen-Huynh, Mai N.; Johnston, S. Claiborne; Smith, Wade S.] UCSF, San Francisco, CA USA. [Furie, Karen L.; Lev, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E314 EP E314 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100483 ER PT J AU Romero, JR Schwamm, LH Frey, JL Demaerschalk, BM Chaliki, HP Parikh, G Babikian, V AF Romero, Jose Rafael Schwamm, Lee H. Frey, James L. Demaerschalk, Bart M. Chaliki, Hari P. Parikh, Gunjan Babikian, Viken TI Safety of TCD "Bubble Study" Response SO STROKE LA English DT Letter C1 [Romero, Jose Rafael; Babikian, Viken] Boston Univ, Med Ctr, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Romero, Jose Rafael] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Schwamm, Lee H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Frey, James L.; Parikh, Gunjan] Barrow Neurol Inst, Div Neurol, Phoenix, AZ 85013 USA. [Demaerschalk, Bart M.; Chaliki, Hari P.] Mayo Clin Hosp, Dept Neurol, Phoenix, AZ USA. RP Romero, JR (reprint author), Boston Univ, Med Ctr, Sch Med, Dept Neurol, Boston, MA 02118 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E196 EP E196 DI 10.1161/STROKEAHA.109.563668 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100063 ER PT J AU Sale, MM Hsu, FC Mychaleckyj, JC Rich, SS Furie, KL Worrall, BB AF Sale, Michele M. Hsu, Fang-Chi Mychaleckyj, Josyf C. Rich, Stephen S. Furie, Karen L. Worrall, Bradford B. TI A Variant in the Adenosine 2B Receptor Gene is Associated With Homocysteine Levels and Stroke Severity in African American Subjects From the Vitamin Intervention for Stroke Prevention (VISP) Trial SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Sale, Michele M.; Mychaleckyj, Josyf C.; Rich, Stephen S.; Worrall, Bradford B.] Univ Virginia, Charlottesville, VA USA. [Hsu, Fang-Chi] Wake Forest Univ, Winston Salem, NC 27109 USA. [Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Furie, Karen L.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E334 EP E334 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100562 ER PT J AU Schaefer, P Kamalian, S Kamalian, MS Wang, B Yoo, A Gonzalez, RG Lev, MH AF Schaefer, Pamela Kamalian, Shahmir Kamalian, Mohammed S. Wang, Bing Yoo, ALbert Gonzalez, Ramon G. Lev, Michael H. TI Infarct Core Size Greater Than 58 cc on Thresholded CT Cerebral Blood Flow Maps is Highly Correlated With Poor Outcome SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Schaefer, Pamela; Kamalian, Shahmir; Kamalian, Mohammed S.; Wang, Bing; Yoo, ALbert; Gonzalez, Ramon G.; Lev, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kamalian, Shervin/D-7667-2013 OI Kamalian, Shervin/0000-0001-8962-4773 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E344 EP E344 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100595 ER PT J AU Silva, G Smith, EE Topcuoglu, MA Singhal, AB AF Silva, Gisele Smith, Eric E. Topcuoglu, Mehmet A. Singhal, Aneesh B. TI Paradoxical Responses on Breath-holding TCD in Reversible Cerebral Vasoconstriction Syndromes (RCVS) SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Silva, Gisele; Singhal, Aneesh B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. [Topcuoglu, Mehmet A.] Hacettepe Univ, Ankara, Turkey. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E316 EP E316 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100491 ER PT J AU Singhal, AB Hajj-Ali, RA Topcuoglu, MA Fok, JW Bena, J Yang, DS Calabrese, LH AF Singhal, Aneesh B. Hajj-Ali, Rula A. Topcuoglu, Mehmet A. Fok, Joshua W. Bena, James Yang, Dongsheng Calabrese, Leonard H. TI Empiric Immunosuppressive Therapy in Reversible Cerebral Vasoconstriction Syndromes (RCVS) is Associated With Worse Clinical Outcome SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Singhal, Aneesh B.; Fok, Joshua W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hajj-Ali, Rula A.; Bena, James; Yang, Dongsheng; Calabrese, Leonard H.] Cleveland Clin, Cleveland, OH 44106 USA. [Topcuoglu, Mehmet A.] Hacettepe Univ Hosp, Ankara, Turkey. 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E233 EP E233 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100182 ER PT J AU Smith, EE Shobha, N Dai, D Olson, D Reeves, MJ Saver, J Peterson, ED Hernandez, A Fonarow, GC Schwamm, LH AF Smith, Eric E. Shobha, Nandavar Dai, David Olson, DaWai Reeves, Mathew J. Saver, Jeffrey Peterson, Eric D. Hernandez, Adrian Fonarow, Gregg C. Schwamm, Lee H. TI Prediction of In-hospital Stroke Mortality Using Data From the Get With the Guidelines-Stroke Registry SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Smith, Eric E.; Shobha, Nandavar] Univ Calgary, Calgary, AB, Canada. [Dai, David; Olson, DaWai; Peterson, Eric D.; Hernandez, Adrian] Duke Clin Rsch Inst, Durham, NC USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Saver, Jeffrey; Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E220 EP E220 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100137 ER PT J AU Souza, LC Payabvash, S Wang, YF Kamalian, S Gonzalez, RG Furie, KL Lev, MH AF Souza, Leticia C. Payabvash, Seyedmehdi Wang, Yifei Kamalian, Shahmir Gonzalez, R. Gilberto Furie, Karen L. Lev, Michael H. TI CT Perfusion Imaging (CTP) Mean Transit Time Prolongation, NIH Stroke Scale Score, and Thrombolytic Therapy Are Independent Predictors of Hemorrhagic Transformation (HT) in Acute Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Souza, Leticia C.; Payabvash, Seyedmehdi; Kamalian, Shahmir; Gonzalez, R. Gilberto; Furie, Karen L.; Lev, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, Yifei] Univ Western Ontario, Schulich Sch Med & Dent, London, ON, Canada. RI Kamalian, Shervin/D-7667-2013 OI Kamalian, Shervin/0000-0001-8962-4773 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E311 EP E311 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100473 ER PT J AU Wu, GX Chilcote, TJ Sinha, S Feener, EP AF Wu, Gongxiong Chilcote, Tamie J. Sinha, Sukanto Feener, Edward P. TI Role of Plasma Kallikrein on Ischemic Stroke in Diabetic Rats SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Wu, Gongxiong; Feener, Edward P.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wu, Gongxiong; Feener, Edward P.] Harvard Univ, Sch Med, Boston, MA USA. [Chilcote, Tamie J.; Sinha, Sukanto] ActiveSite Pharmaceut Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E354 EP E354 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100636 ER PT J AU Wu, O Schwamm, LH Garg, P Pervez, MA Yoo, AJ Chutinet, A Irie, RE Yook, B Copen, WA Schaefer, PW Singhal, AB Furie, KL Sorensen, AG AF Wu, Ona Schwamm, Lee H. Garg, Priya Pervez, Muhammad A. Yoo, Albert J. Chutinet, Aurauma Irie, Robert E. Yook, Byeongseo Copen, William A. Schaefer, Pamela W. Singhal, Aneesh B. Furie, Karen L. Sorensen, A. G. TI Using MRI as the Witness: Multimodal MRI-based Determination of Acute Stroke Onset SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Wu, Ona; Schwamm, Lee H.; Garg, Priya; Pervez, Muhammad A.; Yoo, Albert J.; Chutinet, Aurauma; Irie, Robert E.; Yook, Byeongseo; Copen, William A.; Schaefer, Pamela W.; Singhal, Aneesh B.; Furie, Karen L.; Sorensen, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E273 EP E273 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100330 ER PT J AU Wu, O Batista, LM Lima, FO Furie, KL Greer, DM AF Wu, Ona Batista, Leonardo M. Lima, Fabricio O. Furie, Karen L. Greer, David M. TI Predicting Clinical Outcome in Comatose Cardiac Arrest Patients Using Early CT SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Wu, Ona; Batista, Leonardo M.; Lima, Fabricio O.; Furie, Karen L.; Greer, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E238 EP E239 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100203 ER PT J AU Yavagal, D Drazin, D Gifford, E Edgell, R Rayes, M Xavier, A Hussain, MS Gupta, R Kalia, J Zaidat, OO Linfante, I Nogueira, R Nguyen, T Boulos, A AF Yavagal, Dileep Drazin, Doniel Gifford, Edward Edgell, Randall Rayes, Mahmood Xavier, Andrew Hussain, Muhammad S. Gupta, Rishi Kalia, Junaid Zaidat, Osama O. Linfante, Italo Nogueira, Raul Nguyen, Thanh Boulos, Alan TI US Multicenter Study of Endovascular Therapy in Ruptured Cerebral Aneurysms With Partent Artery Vasospasm SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Yavagal, Dileep] Univ Miami, Miller Sch, Miami, FL USA. [Drazin, Doniel] Cedars Sinai Med Cntr, Los Angeles, CA USA. [Gifford, Edward; Boulos, Alan] Albany Med Cntr, Albany, NY USA. [Edgell, Randall] St Louis Univ, St Louis, MO 63103 USA. [Rayes, Mahmood; Xavier, Andrew] Wayne State Univ, Detroit, MI USA. [Hussain, Muhammad S.; Gupta, Rishi] Cleveland Clin, Cleveland, OH 44106 USA. [Kalia, Junaid; Zaidat, Osama O.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Linfante, Italo] Baptist Med Cntr, Miami, FL USA. [Nogueira, Raul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nguyen, Thanh] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E237 EP E237 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100199 ER PT J AU Zaganas, I Halpin, AP Oleink, A Kotzamani, D Chlapoutaki, C Tsimoulis, D Zafiris, S Giannakoudakis, E Alegakis, A Papadaki, E Furie, KL Greenberg, SM Plaitakis, A AF Zaganas, Ioannis Halpin, Amy P. Oleink, Alexandra Kotzamani, Dimitra Chlapoutaki, Chryssanthi Tsimoulis, Dimitris Zafiris, Spiros Giannakoudakis, Emmanouil Alegakis, Athanasios Papadaki, Efrosini Furie, Karen L. Greenberg, Steven M. Plaitakis, Andreas TI A Comparison of Acute Hemorrhagic Stroke Outcomes in Two Populations: The Crete-Boston Study SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Zaganas, Ioannis; Kotzamani, Dimitra; Chlapoutaki, Chryssanthi; Tsimoulis, Dimitris; Zafiris, Spiros; Giannakoudakis, Emmanouil; Plaitakis, Andreas] Univ Hosp Crete, Dept Neurol, Iraklion, Crete, Greece. [Papadaki, Efrosini] Univ Hosp Crete, Dept Radiol, Iraklion, Crete, Greece. [Alegakis, Athanasios] Univ Hosp Crete, Dept Toxicol, Iraklion, Crete, Greece. [Halpin, Amy P.; Oleink, Alexandra; Furie, Karen L.; Greenberg, Steven M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E212 EP E212 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100105 ER PT J AU Meeker, JD Hauser, R AF Meeker, John D. Hauser, Russ TI Exposure to Polychlorinated Biphenyls (PCBs) and Male Reproduction SO SYSTEMS BIOLOGY IN REPRODUCTIVE MEDICINE LA English DT Review DE endocrine; environment; epidemiology; hormone; semen; sperm ID SPERM CHROMATIN INTEGRITY; TESTICULAR CANCER; FISH CONSUMPTION; SEMEN QUALITY; HUMAN HEALTH; PERSISTENT ORGANOCHLORINES; ENVIRONMENTAL EXPOSURE; CONSTRUCTION WORKERS; ENDOGENOUS HORMONES; EUROPEAN COUNTRIES AB Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants that were widely used in the mid-20th century. Though their production and use was banned by most countries several decades ago, the general population continues to be exposed due to the persistence and bioaccumulation of PCBs. A number of human epidemiological studies have assessed the relationship between environmental PCB exposure and markers of male reproductive health, namely semen quality parameters (sperm concentration, motility, and morphology), sperm DNA integrity (DNA damage or chromatin fragmentation), and circulating reproductive hormone levels. Despite a wide range of study designs and locations, measurement methods, and PCB exposure levels, reports of inverse associations between PCBs and sperm motility have been consistent which may suggest a lack of exposure threshold for a PCB-related effect on sperm motility. Several studies have also reported inverse associations between PCBs and circulating testosterone levels in men, though the specific form of testosterone (i.e. total, bound, or free testosterone) associated with exposure has not been fully consistent between studies. In conclusion, although PCBs are no longer used and can be considered a legacy chemical, concerns regarding altered male fertility in relation to PCBs remain due to the existing human data demonstrating inverse associations with markers of male reproductive function coupled with recent evidence for continued population exposure.= 3 compared with 2 drinks/drinking day. Conclusions In 9 nationally representative samples of U. S. adults, light and moderate alcohol consumption were inversely associated with CVD mortality, even when compared with lifetime abstainers, but consumption above recommended limits was not. (J Am Coll Cardiol 2010; 55: 1328-35) (C) 2010 by the American College of Cardiology Foundation C1 [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Chen, Chiung M.] CSR Inc, Arlington, VA USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Breslow, Rosalind A.] NIAAA, Div Epidemiol & Prevent Res, Rockville, MD 20852 USA. RP Mukamal, KJ (reprint author), BIDMC, Div Gen Med & Primary Care, Res Program, 1309 Beacon St,2nd Floor, Brookline, MA 02446 USA. EM kmukamal@bidmc.harvard.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [N0AA32007, HHSN267200800023C]; GE Corporate Healthcare FX From the *Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts; dagger CSR Incorporated, Arlington, Virginia; Biostatistics Center and Institute for Health Policy, Massachusetts General Hospital, Boston, Massachusetts; and the Division of Epidemiology and Prevention Research, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland. Computer programming and statistical support were provided through the Alcohol Epidemiologic Data System funded by contracts N0AA32007 and HHSN267200800023C from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The NIAAA reviewed and approved this report before submission. The findings and conclusions in this report are those of the authors and not necessarily those of the agency. Dr. Rao has received funding from GE Corporate Healthcare. NR 53 TC 80 Z9 81 U1 2 U2 7 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 MAR 30 PY 2010 VL 55 IS 13 BP 1328 EP 1335 DI 10.1016/j.jacc.2009.10.056 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 573CL UT WOS:000275885900006 PM 20338493 ER PT J AU Maron, DJ Boden, WE O'Rourke, RA Hartigan, PM Calfas, KJ Mancini, GBJ Spertus, JA Dada, M Kostuk, WJ Knudtson, M Harris, CL Sedlis, SP Zoble, RG Title, LM Gosselin, G Nawaz, S Gau, GT Blaustein, AS Bates, ER Shaw, LJ Berman, DS Chaitman, BR Weintraub, WS Teo, KK AF Maron, David J. Boden, William E. O'Rourke, Robert A. Hartigan, Pamela M. Calfas, Karen J. Mancini, G. B. John Spertus, John A. Dada, Marcin Kostuk, William J. Knudtson, Merril Harris, Crystal L. Sedlis, Steven P. Zoble, Robert G. Title, Lawrence M. Gosselin, Gilbert Nawaz, Shah Gau, Gerald T. Blaustein, Alvin S. Bates, Eric R. Shaw, Leslee J. Berman, Daniel S. Chaitman, Bernard R. Weintraub, William S. Teo, Koon K. CA COURAGE Trial Res Grp TI Intensive Multifactorial Intervention for Stable Coronary Artery Disease Optimal Medical Therapy in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE coronary disease; medical therapy; risk factors; secondary prevention ID CONVERTING ENZYME-INHIBITORS; ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-LIFE; RANDOMIZED-TRIALS; SECONDARY PREVENTION; GLUCOSE CONTROL; HEART-DISEASE; DIET-HEART; TASK-FORCE; METAANALYSIS AB Objectives This paper describes the medical therapy used in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial and its effect on risk factors. Background Most cardiovascular clinical trials test a single intervention. The COURAGE trial tested multiple lifestyle and pharmacologic interventions (optimal medical therapy) with or without percutaneous coronary intervention in patients with stable coronary disease. Methods All patients, regardless of treatment assignment, received equivalent lifestyle and pharmacologic interventions for secondary prevention. Most medications were provided at no cost. Therapy was administered by nurse case managers according to protocols designed to achieve predefined lifestyle and risk factor goals. Results The patients (n = 2,287) were followed for 4.6 years. There were no significant differences between treatment groups in proportion of patients achieving therapeutic goals. The proportion of smokers decreased from 23% to 19% (p = 0.025), those who reported <7% of calories from saturated fat increased from 46% to 80% (p < 0.001), and those who walked >= 150 min/week increased from 58% to 66% (p < 0.001). Body mass index increased from 28.8 +/- 0.13 kg/m(2) to 29.3 +/- 0.23 kg/m(2) (p < 0.001). Appropriate medication use increased from pre-randomization to 5 years as follows: antiplatelets 87% to 96%; beta-blockers 69% to 85%; renin-angiotensin-aldosterone system inhibitors 46% to 72%; and statins 64% to 93%. Systolic blood pressure decreased from a median of 131 +/- 0.49 mm Hg to 123 +/- 0.88 mm Hg. Low-density lipoprotein cholesterol decreased from a median of 101 +/- 0.83 mg/dl to 72 +/- 0.88 mg/dl. Conclusions Secondary prevention was applied equally and intensively to both treatment groups in the COURAGE trial by nurse case managers with treatment protocols and resulted in significant improvement in risk factors. Optimal medical therapy in the COURAGE trial provides an effective model for secondary prevention among patients with chronic coronary disease. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657) (J Am Coll Cardiol 2010; 55: 1348-58) (C) 2010 by the American College of Cardiology Foundation C1 [Maron, David J.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Maron, David J.] Vanderbilt Univ, Sch Med, Dept Emergency Med, Nashville, TN 37212 USA. [Boden, William E.] SUNY Buffalo, Buffalo, NY 14260 USA. [Boden, William E.] Buffalo Gen Hosp, Buffalo, NY 14203 USA. [O'Rourke, Robert A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Hartigan, Pamela M.] VA Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA. [Calfas, Karen J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Mancini, G. B. John] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Spertus, John A.] Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA. [Kostuk, William J.] London Hlth Sci Ctr, London, ON, Canada. [Dada, Marcin] Hartford Hosp, Hartford, CT 06115 USA. [Knudtson, Merril] Libin Cardiovasc Inst Alberta, Edmonton, AB, Canada. [Harris, Crystal L.] VA Cooperat Studies Program, Albuquerque, NM USA. [Sedlis, Steven P.] NYU, Sch Med, New York, NY USA. [Sedlis, Steven P.] Vet Affairs New York Harbor Hlth Care Syst, New York, NY USA. [Zoble, Robert G.] James A Haley Vet Adm Med Ctr, Tampa, FL 33612 USA. [Title, Lawrence M.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Gosselin, Gilbert] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Nawaz, Shah] Sudbury Reg Hosp, Sudbury, ON, Canada. [Gau, Gerald T.] Mayo Clin, Rochester, MN USA. [Blaustein, Alvin S.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Bates, Eric R.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Shaw, Leslee J.] Emory Univ, Atlanta, GA 30322 USA. [Berman, Daniel S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Chaitman, Bernard R.] St Louis Univ, St Louis, MO 63103 USA. [Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Teo, Koon K.] McMaster Univ, Med Ctr, Hamilton, ON, Canada. RP Maron, DJ (reprint author), Vanderbilt Heart & Vasc Inst, 1215 21st Ave S,MCE 5th Floor S Tower, Nashville, TN 37232 USA. EM david.maron@vanderbilt.edu OI Sedlis, Steven/0000-0002-8194-8017 FU Merck; Abbott Laboratories; Amgen; Roche Diagnostics; Lilly; CV Therapeutics; Bristol-Myers Squibb; Astellas Healthcare; Sanofi-Aventis; Boehringer Ingelheim FX Dr. Boden has received consulting fees and lecture fees from Kos Pharmaceuticals, PDL BioPharma, Pfizer, CV Therapeutics, and Sanofi-Aventis and grant support from Merck and Abbott Laboratories. Dr. O'Rourke has received consulting fees from King Pharmaceuticals, Lilly, and CV Therapeutics. Dr. Calfas has been a stockholder of SanTech, Inc. a company founded in cooperation with San Diego State University and exclusively licensed to disseminate the PACE materials. Dr. Mancini has received honoraria from Merck, GlaxoSmithKline, Sanofi-Aventis, AstraZeneca and Abbott. Dr. Spertus has received consulting fees from Amgen and United Healthcare and grant support from Amgen, Roche Diagnostics, and Lilly (and in the past, consulting fees and grant support from CV Therapeutics and has been owner of the copyright for the Seattle Angina Questionnaire, the Peripheral Artery Questionnaire, and the Kansas City Cardiomyopathy Questionnaire). Dr. Bates has received consulting fees from Sanofi-Aventis and AstraZeneca and lecture fees from Sanofi-Aventis. Dr. Shaw has received grant support from Bristol-Myers Squibb and Astellas Healthcare. Dr. Berman has received consulting fees, lecture fees, and grant support from Bristol-Myers Squibb and software royalties from Cedars Sinai Medical Center. Dr. Chaitman has received consulting fees from CV Therapeutics, Roche, Merck, Lilly, Sanofi-Aventis, Forest; lecture fees from CV Therapeutics; and research grants from Roche and CV Therapeutics. Dr. Weintraub has received consulting fees from Sanofi-Aventis and Bristol-Myers Squibb and grant support from Sanofi-Aventis. Dr. Teo has received grant support from Boehringer Ingelheim. NR 50 TC 50 Z9 52 U1 1 U2 14 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 MAR 30 PY 2010 VL 55 IS 13 BP 1348 EP 1358 DI 10.1016/j.jacc.2009.10.062 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 573CL UT WOS:000275885900009 PM 20338496 ER PT J AU Cornier, MA Salzberg, AK Endly, DC Bessesen, DH Tregellas, JR AF Cornier, Marc-Andre Salzberg, Andrea K. Endly, Dawnielle C. Bessesen, Daniel H. Tregellas, Jason R. TI Sex-based differences in the behavioral and neuronal responses to food SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE fMRI; Neuroimaging; Obesity; Food intake; Gender; Appetite ID REDUCED-OBESE INDIVIDUALS; BODY-WEIGHT; GENDER-DIFFERENCES; BRAIN ACTIVATION; OVARIECTOMIZED RATS; ESTRADIOL DECREASES; DIETARY RESTRAINT; PREFRONTAL CORTEX; ENERGY-BALANCE; FEMALE RATS AB Sex-based differences in food intake related behaviors have been observed previously. The objective of this study was to examine sex-based differences in the behavioral and neuronal responses to food. 22 women and 21 men were studied. After 6 days of controlled eucaloric feeding, ad libitum energy intake (El) was measured for 3 days. Appetite ratings using visual analog scales were obtained before and after each meal. Functional magnetic resonance imaging was performed in the overnight fasted state on the last day of eucaloric feeding while subjects were presented visual stimuli of food and neutral non-food objects. While hunger and prospective consumption were not different between sexes, women had higher post-meal satiety ratings and dietary restraint than men. Images of hedonic foods resulted in significantly greater activation of lateral and dorsolateral prefrontal cortex (DLPFC) and parietal cortex in women as compared to men. No brain regions were more activated in men as compared to women. Men increased their El during the ad libitum diet phase. While measures of appetite or feeding behaviors did not correlate with either neuronal activation or subsequent El. DLPFC activation in response to hedonic foods was negatively correlated with El. In summary, greater prefrontal neuronal responses to food cues in women may suggest increased cognitive processing related to executive function, such as planning, guidance or evaluation of behavior. Finally, increased DLPFC activation, perhaps relating to inhibitory cognitive control in response to food cues may be a better predictor of food intake than behavioral measures. (C) 2010 Elsevier Inc. All rights reserved. C1 [Cornier, Marc-Andre; Salzberg, Andrea K.; Endly, Dawnielle C.; Bessesen, Daniel H.] Univ Colorado Denver, Div Endocrinol Diabet & Metab, Dept Med, Aurora, CO 80045 USA. [Tregellas, Jason R.] Univ Colorado Denver, Dept Psychiat, Aurora, CO 80045 USA. [Cornier, Marc-Andre; Bessesen, Daniel H.] Denver Hlth Med Ctr, Dept Med, Denver, CO 80204 USA. [Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. RP Cornier, MA (reprint author), Univ Colorado Denver, Div Endocrinol Diabet & Metab, Dept Med, Mail Stop 8106,12801 E 17th Ave,Room 7103, Aurora, CO 80045 USA. EM marc.cornier@ucdenver.edu RI Tregellas, Jason/J-3637-2015 FU NIH/NCRR Colorado CTSI [UL1 RR025780]; NIH/NIDDK Clinical Nutrition Research Unit [DK48520]; NIH/NCRR [RR016185] FX We acknowledge and thank Debra Singel and Yiping Du for their assistance with the fMRI studies. We also thank the dietary services and metabolic kitchen of the University of Colorado Denver CTRC. This publication was supported by NIH/NCRR Colorado CTSI grant number UL1 RR025780, NIH/NIDDK Clinical Nutrition Research Unit grant number DK48520, and NIH/NCRR grant number RR016185. Its contents are the authors' sole responsibility and do not necessarily represent official NIH views. NR 53 TC 76 Z9 76 U1 7 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD MAR 30 PY 2010 VL 99 IS 4 BP 538 EP 543 DI 10.1016/j.physbeh.2010.01.008 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 576KQ UT WOS:000276143700018 PM 20096712 ER PT J AU Feuerer, M Hill, JA Kretschmer, K von Boehmer, H Mathis, D Benoist, C AF Feuerer, Markus Hill, Jonathan A. Kretschmer, Karsten von Boehmer, Harald Mathis, Diane Benoist, Christophe TI Genomic definition of multiple ex vivo regulatory T cell subphenotypes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Foxp3; microarray ID TRANSCRIPTION FACTOR FOXP3; TGF-BETA; RETINOIC-ACID; IN-VIVO; INDUCTION; ANTIGEN; TOLERANCE; RESPONSES; LINEAGE; MICE AB Regulatory T (Treg) cells that express the Foxp3 transcription factor are essential for lymphoid homeostasis and immune tolerance to self. Other nonimmunological functions of Treg cells, such as controlling metabolic function in adipose tissue, are also emerging. Treg cells originate primarily in the thymus, but can also be elicited from conventional T cells by in vivo exposure to low-dose antigen or homeostatic expansion or by activation in the presence of TGF beta in vitro. Treg cells are characterized by a distinct transcriptional signature controlled in part, but not solely, by Foxp3. For a better perspective on transcriptional control in Treg cells, we compared gene expression profiles of a broadpanel of Treg cells from various origins or anatomical locations. Treg cells generated by different means form different subphenotypes and were identifiable by particular combinations of transcripts, none of which fully encompassed the entire Treg signature. Molecules involved in Treg cell effector function, chemokine receptors, and the transcription factors that control them were differentially represented in these subphenotypes. Treg cells from the gut proved dissimilar to cells elicited by exposure to TGF beta in vitro, but instead they resembled a CD103(+)Klrg1(+) subphenotype preferentially generated in response to lymphopenia. C1 [Feuerer, Markus; Hill, Jonathan A.; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Feuerer, Markus; Hill, Jonathan A.; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. [Kretschmer, Karsten; von Boehmer, Harald] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM cbdm@hms.harvard.edu RI Kretschmer, Karsten/E-8174-2010 FU Juvenile Diabetes Research Foundation [4-2007-1057]; National Institutes of Health [7R01AI51530, R37 AI053102]; Joslin Diabetes Center's National Institute of Diabetes and Digestive; Digestive and Kidney Diseases; German Research Foundation [FE 801/1-1]; Charles A. King Trust Postdoctoral Fellowship; Canadian Institutes of Health Research; Canadian Diabetes Association FX We thank J. Pagan and K. Hattori for assistance with mice, J. LaVecchio and G. Buruzala for help with cytometry, J. Perez and K. Leatherbee for microarrays, and S. Davis for computational analysis. This work was supported by grants from the Juvenile Diabetes Research Foundation (4-2007-1057) and the National Institutes of Health (7R01AI51530), by Joslin Diabetes Center's National Institute of Diabetes and Digestive and Kidney Diseases-funded Diabetes Endocrinology Research Care core facilities (D. M. and C. B.), and by National Institutes of Health Grant R37 AI053102 (to H. v. B.). M. F. was supported by postdoctoral fellowships from the German Research Foundation (Emmy-Noether Fellowship, FE 801/1-1) and the Charles A. King Trust Postdoctoral Fellowship. J. A. H. was supported by a postdoctoral fellowship from the Canadian Institutes of Health Research and the Canadian Diabetes Association. NR 47 TC 121 Z9 121 U1 0 U2 8 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 MAR 30 PY 2010 VL 107 IS 13 BP 5919 EP 5924 DI 10.1073/pnas.1002006107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 576QA UT WOS:000276159500042 PM 20231436 ER PT J AU Burgdorf, S Schuette, V Semmling, V Hochheiser, K Lukacs-Kornek, V Knolle, PA Kurts, C AF Burgdorf, Sven Schuette, Verena Semmling, Verena Hochheiser, Katharina Lukacs-Kornek, Veronika Knolle, Percy A. Kurts, Christian TI Steady-state cross-presentation of OVA is mannose receptor-dependent but inhibitable by collagen fragments SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID ANTIGEN; PATHWAYS C1 [Burgdorf, Sven; Schuette, Verena; Semmling, Verena; Hochheiser, Katharina; Knolle, Percy A.; Kurts, Christian] Univ Hosp Bonn, Inst Mol Med, D-53105 Bonn, Germany. [Burgdorf, Sven; Schuette, Verena; Semmling, Verena; Hochheiser, Katharina; Knolle, Percy A.; Kurts, Christian] Univ Hosp Bonn, Inst Expt Immunol, D-53105 Bonn, Germany. [Lukacs-Kornek, Veronika] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Burgdorf, S (reprint author), Univ Hosp Bonn, Inst Mol Med, D-53105 Bonn, Germany. EM sven.burgdorf@ukb.uni-bonn.de; ckurts@web.de OI Knolle, Percy A./0000-0003-2983-0414 NR 5 TC 20 Z9 20 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 MAR 30 PY 2010 VL 107 IS 13 BP E48 EP E49 DI 10.1073/pnas.1000598107 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 576QA UT WOS:000276159500082 PM 20308535 ER PT J AU Egede, LE Strom, JL Durkalski, VL Mauldin, PD Moran, WP AF Egede, Leonard E. Strom, Joni L. Durkalski, Valerie L. Mauldin, Patrick D. Moran, William P. TI Rationale and design: telephone-delivered behavioral skills interventions for Blacks with type 2 diabetes SO TRIALS LA English DT Article ID FUNCTIONAL HEALTH LITERACY; URBAN AFRICAN-AMERICANS; PRIMARY-CARE PROVIDERS; PHYSICAL-ACTIVITY; SELF-MANAGEMENT; UNITED-STATES; PSYCHOMETRIC PROPERTIES; CLINICAL INERTIA; GLYCEMIC CONTROL; QUESTIONNAIRE AB Background: African Americans with Type 2 diabetes (T2DM) have higher prevalence of diabetes, poorer metabolic control, and greater risk for complications and death compared to American Whites. Poor outcomes in African Americans with T2DM can be attributed to patient, provider, and health systems level factors. Provider and health system factors account for <10% of variance in major diabetes outcomes including hemoglobin A1c (HbA1c), lipid control, and resource use. Key differences appear to be at the patient level. Of the patient level factors, consistent differences between African Americans and American Whites with T2DM have been found in diabetes knowledge, self-management skills, empowerment, and perceived control. A variety of interventions to improve diabetes self-management have been tested including: 1) knowledge interventions; 2) lifestyle interventions; 3) skills training interventions; and 4) patient activation and empowerment interventions. Most of these interventions have been tested individually, but rarely have they been tested in combination, especially among African Americans who have the greatest burden of diabetes related complications. This study provides a unique opportunity to address this gap in the literature. Methods/Design: We describe an ongoing four-year randomized clinical trial, using a 2 x 2 factorial design, which will test the efficacy of separate and combined telephone-delivered, diabetes knowledge/information and motivation/behavioral skills training interventions in high risk African Americans with poorly controlled T2DM (HbA1c = 9%). Two-hundred thirty-two (232) male and female African-American participants, 18 years of age or older and with an HbA1c = 9%, will be randomized into one of four groups for 12-weeks of phone interventions: (1) an education group, (2) a motivation/skills group, (3) a combined group or (4) a usual care/general health education group. Participants will be followed for 12-months to ascertain the effect of the interventions on glycemic control. Our primary hypothesis is that among African Americans with poorly controlled T2DM, patients randomized to the combined diabetes knowledge/information and motivation/behavioral skills training intervention will have significantly greater reduction in HbA1c at 12 months of follow-up compared to the usual care/general health education group. Discussion: Results from this study will provide important insight into how best to deliver diabetes education and skills training in ethnic minorities and whether combined knowledge/information and motivation/behavioral skills training is superior to the usual method of delivering diabetes education for African Americans with poorly controlled T2DM. C1 [Egede, Leonard E.; Mauldin, Patrick D.] Ctr Dis Prevent & Hlth Intervent Diverse Populat, Ralph H Johnson VAMC, Charleston, SC USA. [Egede, Leonard E.; Strom, Joni L.; Moran, William P.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Egede, Leonard E.; Strom, Joni L.; Mauldin, Patrick D.; Moran, William P.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Durkalski, Valerie L.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Mauldin, Patrick D.] Med Univ S Carolina, Dept Clin Pharm & Outcome Sci, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Ctr Dis Prevent & Hlth Intervent Diverse Populat, Ralph H Johnson VAMC, Charleston, SC USA. EM egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK081121-01A1] FX The study is funded by grant # R01DK081121-01A1 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). NR 48 TC 4 Z9 4 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD MAR 29 PY 2010 VL 11 AR 35 DI 10.1186/1745-6215-11-35 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 584MF UT WOS:000276755400001 PM 20350322 ER PT J AU Hu, YD Lu, XC Luo, GB AF Hu, Yiduo Lu, Xincheng Luo, Guangbin TI Effect of Recql5 deficiency on the intestinal tumor susceptibility of Apc(min) mice SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Recql5; Apc; Tumor suppressor; Genome instability; Colon cancer; Apc(min/+) mice ID RNA-POLYMERASE-II; CANCER; TRANSCRIPTION; EPITHELIUM; ANEUPLOIDY; SUPPRESSOR; GENES AB AIM: To investigate whether Recql5, a DNA helicase that plays an important role in the maintenance of genome integrity, is a tumor suppressor in the gastrointestinal tract in mice. METHODS: We generated cohorts of both Recql5-proficient and Recql5-deficient Apc(min/+) mice and compared the tumor susceptibility in their gastrointestinal tracts. RESULTS: Recql5 deficiency in Apc(min/+) mice resulted in a significant increase in the tumor incidence in both the colon (P = 0.0162) and the small intestine (P < 0.01). These findings have provided the first genetic evidence for a tumor suppression role of Recql5 in the gastrointestinal tract of mice. Importantly, since mouse Recql5 and human RECQL5 are highly conserved, these findings also suggest that RECQL5 may be a tumor suppressor for human colon cancer. CONCLUSION: Recql5 has a tumor suppression role in the mouse gastrointestinal tract. (C) 2010 Baishideng. All rights reserved. C1 [Hu, Yiduo; Lu, Xincheng; Luo, Guangbin] Case Western Reserve Univ, Case Comprehens Canc Ctr, Dept Genet, Cleveland, OH 44106 USA. [Hu, Yiduo; Lu, Xincheng; Luo, Guangbin] Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Hu, Yiduo] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Luo, GB (reprint author), Case Western Reserve Univ, Case Comprehens Canc Ctr, Dept Genet, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM guangbin.luo@case.edu FU US National Institutes of Health [RO1 CA88939, P20 CA 103736]; Searle Scholar Program [01-E-109] FX Supported by Grants RO1 CA88939, P20 CA 103736 from the US National Institutes of Health and Searle Scholar Award 01-E-109 from the Searle Scholar Program NR 19 TC 7 Z9 10 U1 0 U2 0 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD MAR 28 PY 2010 VL 16 IS 12 BP 1482 EP 1486 DI 10.3748/wjg.v16.i12.1482 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 574TS UT WOS:000276017200009 PM 20333788 ER PT J AU Zhou, WJ Hur, W McDermott, U Dutt, A Xian, W Ficarro, SB Zhang, JM Sharma, SV Brugge, J Meyerson, M Settleman, J Gray, NS AF Zhou, Wenjun Hur, Wooyoung McDermott, Ultan Dutt, Amit Xian, Wa Ficarro, Scott B. Zhang, Jianming Sharma, Sreenath V. Brugge, Joan Meyerson, Matthew Settleman, Jeffrey Gray, Nathanael S. TI A Structure-Guided Approach to Creating Covalent FGFR Inhibitors SO CHEMISTRY & BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; IMATINIB MESYLATE; CANCER; MUTATIONS; PROLIFERATION; SENSITIVITY; ACTIVATION; RESISTANCE; LEUKEMIA AB The fibroblast growth factor receptor tyrosine kinases (FGFR1, 2, 3, and 4) represent promising therapeutic targets in a number of cancers. We have developed the first potent and selective irreversible inhibitor of FGFR1, 2, 3, and 4, which we named FIIN-1 that forms a covalent bond with cysteine 486 located in the P loop of the FGFR1 ATP binding site. We demonstrated that the inhibitor potently inhibits Tel-FGFR1-transformed Ba/F3 cells (EC50 = 14 nM) as well as numerous FGFR-dependent cancer cell lines. A biotin-derivatized version of the inhibitor, FIIN-1-biotin, was shown to covalently label FGFR1 at Cys486. FIIN-1 is a useful probe of FGFR-dependent cellular phenomena and may provide a starting point of the development of therapeutically relevant irreversible inhibitors of wild-type and drug-resistant forms of FGFR kinases. C1 [Zhou, Wenjun; Ficarro, Scott B.; Zhang, Jianming; Gray, Nathanael S.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Biol, Boston, MA 02115 USA. [Dutt, Amit; Meyerson, Matthew] Harvard Univ, Dana Farber Canc Inst, Sch Med, Broad Inst,Dept Med Oncol, Boston, MA 02115 USA. [Hur, Wooyoung] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [McDermott, Ultan; Sharma, Sreenath V.; Settleman, Jeffrey] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Xian, Wa; Brugge, Joan] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Gray, NS (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Biol, Boston, MA 02115 USA. EM nathanael_gray@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Dutt, Amit/I-1911-2013; OI Dutt, Amit/0000-0002-1119-4774; McDermott, Ultan/0000-0001-9032-4700 FU Damon Runyon Cancer Foundation; Mary Kay Ash Foundation; National Science Foundation FX This work was supported by grants from the Damon Runyon Cancer Foundation, the Mary Kay Ash Foundation, and the National Science Foundation. We acknowledge generous assistance from Ambit Biosciences for performing KinomeScan profiling and Invitrogen for performing the Z'-Iyte kinase assays. The authors declare no competing financial interests. NR 47 TC 61 Z9 64 U1 2 U2 38 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 EI 1879-1301 J9 CHEM BIOL JI Chem. Biol. PD MAR 26 PY 2010 VL 17 IS 3 BP 285 EP 295 DI 10.1016/j.chembiol.2010.02.007 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 583MI UT WOS:000276680200011 PM 20338520 ER PT J AU Seker, E Berdichevsky, Y Begley, MR Reed, ML Staley, KJ Yarmush, ML AF Seker, Erkin Berdichevsky, Yevgeny Begley, Matthew R. Reed, Michael L. Staley, Kevin J. Yarmush, Martin L. TI The fabrication of low-impedance nanoporous gold multiple-electrode arrays for neural electrophysiology studies SO NANOTECHNOLOGY LA English DT Article ID MICROELECTRODE ARRAYS; CONDUCTING POLYMERS; NEURONAL NETWORKS; INTERFACES; CULTURE; SYSTEM AB Neural electrodes are essential tools for the study of the nervous system and related diseases. Low electrode impedance is a figure of merit for sensitive detection of neural electrical activity and numerous studies have aimed to reduce impedance. Unfortunately, most of these efforts have been tethered by a combination of poor functional coating adhesion, complicated fabrication techniques, and poor fabrication repeatability. We address these issues with a facile method for reliably producing multiple-electrode arrays with low impedance by patterning highly adherent nanoporous gold films using conventional microfabrication techniques. The high surface area-to-volume ratio of self-assembled nanoporous gold results in a more than 25-fold improvement in the electrode-electrolyte impedance, where at 1 kHz, 850 k Omega impedance for conventional Au electrodes is reduced to 30 k Omega for nanoporous gold electrodes. Low impedance provides a superior signal-to-noise ratio for detection of neural activity in noisy environments. We systematically studied the effect of film morphology on electrode impedance and successfully recorded field potentials from rat hippocampal slices. Here, we present our fabrication approach, the relationship between film morphology and impedance, and field potential recordings. C1 [Seker, Erkin; Berdichevsky, Yevgeny; Yarmush, Martin L.] Harvard Univ, Sch Med, Dept Surg,Shriners Hosp Children, Massachusetts Gen Hosp,Ctr Engn Med, Boston, MA 02115 USA. [Begley, Matthew R.] Univ Calif Santa Barbara, Dept Mech Engn, Santa Barbara, CA 93106 USA. [Reed, Michael L.] Univ Virginia, Dept Elect & Comp Engn, Charlottesville, VA USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Dept Surg,Shriners Hosp Children, Massachusetts Gen Hosp,Ctr Engn Med, Boston, MA 02115 USA. EM ireis@sbi.org OI Seker, Erkin/0000-0003-2401-3562 FU NIH [P41-EB002503, F32-MH079662]; New Jersey Commission on Brain Injury Research [08-3210-BIR-E-1]; NSF [DMI-0507023] FX This work was sponsored in part by NIH Grant P41-EB002503, New Jersey Commission on Brain Injury Research Grant 08-3210-BIR-E-1, and NSF Grant DMI-0507023. YB was supported by NIH F32-MH079662. NR 26 TC 40 Z9 40 U1 4 U2 31 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0957-4484 J9 NANOTECHNOLOGY JI Nanotechnology PD MAR 26 PY 2010 VL 21 IS 12 AR 125504 DI 10.1088/0957-4484/21/12/125504 PG 7 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Science & Technology - Other Topics; Materials Science; Physics GA 564OH UT WOS:000275224100015 PM 20203356 ER PT J AU Wang, YZ Krivtsov, AV Sinha, AU North, TE Goessling, W Feng, ZH Zon, LI Armstrong, SA AF Wang, Yingzi Krivtsov, Andrei V. Sinha, Amit U. North, Trista E. Goessling, Wolfram Feng, Zhaohui Zon, Leonard I. Armstrong, Scott A. TI The Wnt/beta-Catenin Pathway Is Required for the Development of Leukemia Stem Cells in AML SO SCIENCE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; BETA-CATENIN; COLON-CANCER; HEMATOPOIETIC-CELLS; SIGNALING PATHWAY; IN-VIVO; PROGENITORS; EXPRESSION; EXPANSION; RENEWAL AB Leukemia stem cells (LSCs) are capable of limitless self-renewal and are responsible for the maintenance of leukemia. Because selective eradication of LSCs could offer substantial therapeutic benefit, there is interest in identifying the signaling pathways that control their development. We studied LSCs in mouse models of acute myelogenous leukemia (AML) induced either by coexpression of the Hoxa9 and Meis1a oncogenes or by the fusion oncoprotein MLL-AF9. We show that the Wnt/beta-catenin signaling pathway is required for self-renewal of LSCs that are derived from either hematopoietic stem cells (HSC) or more differentiated granulocyte-macrophage progenitors (GMP). Because the Wnt/beta-catenin pathway is normally active in HSCs but not in GMP, these results suggest that reactivation of beta-catenin signaling is required for the transformation of progenitor cells by certain oncogenes. beta-catenin is not absolutely required for self-renewal of adult HSCs; thus, targeting the Wnt/beta-catenin pathway may represent a new therapeutic opportunity in AML. C1 [Wang, Yingzi; Krivtsov, Andrei V.; Sinha, Amit U.; Feng, Zhaohui; Zon, Leonard I.; Armstrong, Scott A.] Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. [Sinha, Amit U.; Feng, Zhaohui; Armstrong, Scott A.] Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. [North, Trista E.] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Dept Pathol, Boston, MA 02115 USA. [North, Trista E.; Goessling, Wolfram; Zon, Leonard I.; Armstrong, Scott A.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Zon, Leonard I.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Armstrong, SA (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. EM scott.armstrong@childrens.harvard.edu OI Goessling, Wolfram/0000-0001-9972-1569 FU NIH [5P01CA66996, 5R01HL048801]; American Cancer Society [RSG-09-068-01]; Harvard Stem Cell Institute FX We thank D. Fisher, X. He, and H. Widlund for plasmid pcDNA3.1-beta cat-*-Flag; D. Williams for helpful discussion and advice; and M. Smith for administrative assistance. This work was supported by the NIH grants 5P01CA66996 ( to S. A. A.) and 5R01HL048801 ( to L.I.Z.), the American Cancer Society (RSG-09-068-01), and the Harvard Stem Cell Institute. S. A. A. is a Leukemia and Lymphoma Society Scholar. Microarray data was submitted to the National Center for Biotechnology Information Gene Expression Omnibus (GEO) GSE20377. L.I.Z. is a founding member of and stockholder in Fate Therapeutics, a biotechnology company that is developing stem cell therapeutics and that has acquired a patent covering the use of prostaglandin E2 in hematopoietic stem cell modulation and tissue regeneration. W. G. and T.E.N. are paid consultants for Fate Therapeutics. NR 25 TC 303 Z9 321 U1 2 U2 42 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 MAR 26 PY 2010 VL 327 IS 5973 BP 1650 EP 1653 DI 10.1126/science.1186624 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 574ED UT WOS:000275970600046 PM 20339075 ER PT J AU Rieckmann, T Fuller, BE Saedi, GA McCarty, D AF Rieckmann, Traci Fuller, Bret E. Saedi, Goal Auzeen McCarty, Dennis TI Adoption of practice guidelines and assessment tools in substance abuse treatment SO SUBSTANCE ABUSE TREATMENT PREVENTION AND POLICY LA English DT Article ID DIFFUSION; BELIEFS; STAFF AB Background: The gap between research and practice limits utilization of relevant, progressive and empirically validated strategies in substance abuse treatment. Methods: Participants included substance abuse treatment programs from the Northeastern United States. Structural equation models were constructed with agency level data to explore two outcome variables: adoption of practice guidelines and assessment tools at two points in time; models also included organizational, staffing and service variables. Results: In 1997, managed care involvement and provision of primary care services had the strongest association with increased use of assessment tools, which, along with provision of counseling services, were associated with a greater use of practice guidelines. In 2001, managed care involvement, counseling services and being a stand-alone drug treatment agency were associated with a greater use of assessment tools, which was in turn related to an increase in the use of practice guidelines. Conclusions: This study provides managers, clinicians and policy-makers with a framework for understanding factors related to the adoption of new technologies in substance abuse treatment. C1 [Rieckmann, Traci; McCarty, Dennis] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Fuller, Bret E.] Portland VA Med Ctr, Portland, OR 97239 USA. [Saedi, Goal Auzeen] Univ Notre Dame, Dept Psychol, Notre Dame, IN 46556 USA. RP Rieckmann, T (reprint author), Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, 3181 SW Sam Jackson Pk Rd,Mailcode CB669, Portland, OR 97239 USA. EM rieckman@ohsu.edu FU NIAAA NIH HHS [R01 AA011363, R01-AA11363, R01 AA011363-05]; NIDA NIH HHS [U10 DA013036, K23 DA021225] NR 38 TC 2 Z9 2 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-597X J9 SUBST ABUSE TREAT PR JI Subst/ Abus. Treatment Prev. Pol. PD MAR 26 PY 2010 VL 5 AR 4 DI 10.1186/1747-597X-5-4 PG 9 WC Substance Abuse SC Substance Abuse GA 593BL UT WOS:000277426500001 PM 20346158 ER PT J AU Pollard, JA Alonzo, TA Gerbing, RB Ho, PA Zeng, R Ravindranath, Y Dahl, G Lacayo, NJ Becton, D Chang, M Weinstein, HJ Hirsch, B Raimondi, SC Heerema, NA Woods, WG Lange, BJ Hurwitz, C Arceci, RJ Radich, JP Bernstein, ID Heinrich, MC Meshinchi, S AF Pollard, Jessica A. Alonzo, Todd A. Gerbing, Robert B. Ho, Phoenix A. Zeng, Rong Ravindranath, Yaddanapudi Dahl, Gary Lacayo, Norman J. Becton, David Chang, Myron Weinstein, Howard J. Hirsch, Betsy Raimondi, Susana C. Heerema, Nyla A. Woods, William G. Lange, Beverly J. Hurwitz, Craig Arceci, Robert J. Radich, Jerald P. Bernstein, Irwin D. Heinrich, Michael C. Meshinchi, Soheil TI Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; BONE-MARROW-TRANSPLANTATION; CHILDRENS ONCOLOGY GROUP; RAS GENE-MUTATIONS; C-KIT; CHILDHOOD-AML; IMATINIB MESYLATE; KINASE INHIBITOR; FLT3 MUTATIONS AB KIT receptor tyrosine kinase mutations are implicated as a prognostic factor in adults with core binding factor (CBF) acute myeloid leukemia (AML). However, their prevalence and prognostic significance in pediatric CBF AML is not well established. We performed KIT mutational analysis (exon 8 and exon 17) on diagnostic specimens from 203 pediatric patients with CBF AML enrolled on 4 pediatric AML protocols. KIT mutations were detected in 38 (19%) of 203 (95% CI, 14%-25%) patient samples of which 20 (52.5%) of 38 (95% CI, 36%-69%) involved exon 8, 17 (45%) of 38 (95% CI, 29%-62%) involved exon 17, and 1 (2.5%; 95% CI, 0%-14%) involved both locations. Patients with KIT mutations had a 5-year event-free survival of 55% (+/- 17%) compared with 59% (+/- 9%) for patients with wild-type KIT (P = .86). Rates of complete remission, overall survival, disease-free survival, or relapse were not significantly different for patients with or without KIT mutations. Location of the KIT mutation and analysis by cytogenetic subtype [t(8; 21) vs inv(16)] also lacked prognostic significance. Our study shows that KIT mutations lack prognostic significance in a large series of pediatric patients with CBF AML. This finding, which differs from adult series and a previously published pediatric study, may reflect variations in therapeutic approaches and/or biologic heterogeneity within CBF AML. Two of 4 studies included in this analysis are registered at http://clinicaltrials.gov as NCT00002798(CCG-2961) and NCT00070174 (COG AAML03P1). (Blood. 2010; 115: 2372-2379) C1 [Pollard, Jessica A.; Ho, Phoenix A.; Zeng, Rong; Radich, Jerald P.; Bernstein, Irwin D.; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Pollard, Jessica A.; Ho, Phoenix A.; Bernstein, Irwin D.; Meshinchi, Soheil] Univ Washington, Seattle, WA 98195 USA. [Alonzo, Todd A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Alonzo, Todd A.; Gerbing, Robert B.] Childrens Oncol Grp, Arcadia, CA USA. [Ravindranath, Yaddanapudi] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Dahl, Gary; Lacayo, Norman J.] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. [Becton, David] Univ Arkansas, Little Rock, AR 72204 USA. [Chang, Myron] Childrens Oncol Grp, Gainesville, FL USA. [Weinstein, Howard J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Betsy] Univ Minnesota, Ctr Canc, Minneapolis, MN USA. [Raimondi, Susana C.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Heerema, Nyla A.] Ohio State Univ, Columbus, OH 43210 USA. [Woods, William G.] Emory Univ, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. [Lange, Beverly J.] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Hurwitz, Craig] Maine Med Ctr, Portland, ME 04102 USA. [Arceci, Robert J.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. RP Pollard, JA (reprint author), Seattle Childrens Hosp, Div Heme Onc, 4800 Sandpoint Way NE,MS-B-6553, Seattle, WA 98105 USA. EM jessica.pollard@seattlechildrens.org OI Ho, Phoenix/0000-0003-3786-7583 FU National Cancer Institute [5K12CA076930-08]; St Baldrick's Foundation Career Development Award; CureSearch Research Fellowship Award; For Julie Foundation; VA Merit Review Grant; Leukemia & Lymphoma Society; National Institutes of Health [R21 CA10262-01, R01 CA114563-01]; Children's Oncology Group Chair [NIH U10 CA98543] FX This work was supported by the National Cancer Institute (5K12CA076930-08) (J.A.P.), St Baldrick's Foundation Career Development Award (J.A.P.), CureSearch Research Fellowship Award (J.A.P.), For Julie Foundation Research Grant (J.A.P.), VA Merit Review Grant (M.C.H.), Leukemia & Lymphoma Society (M.C.H.), and the National Institutes of Health (grants R21 CA10262- 01 and R01 CA114563- 01, Children's Oncology Group Chair's grant NIH U10 CA98543). NR 40 TC 78 Z9 82 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 25 PY 2010 VL 115 IS 12 BP 2372 EP 2379 DI 10.1182/blood-2009-09-241075 PG 8 WC Hematology SC Hematology GA 574IF UT WOS:000275981900010 PM 20056794 ER PT J AU Sahin, E DePinho, RA AF Sahin, Erguen DePinho, Ronald A. TI Linking functional decline of telomeres, mitochondria and stem cells during ageing SO NATURE LA English DT Review ID MAMMALIAN LIFE-SPAN; AGE-RELATED-CHANGES; DNA-DAMAGE; DYSFUNCTIONAL TELOMERES; CHROMOSOMAL INSTABILITY; REVERSE-TRANSCRIPTASE; TERMINAL TRANSFERASE; TUMOR SUPPRESSION; OXIDATIVE STRESS; ARF/P53 PATHWAY AB The study of human genetic disorders and mutant mouse models has provided evidence that genome maintenance mechanisms, DNA damage signalling and metabolic regulation cooperate to drive the ageing process. In particular, age-associated telomere damage, diminution of telomere 'capping' function and associated p53 activation have emerged as prime instigators of a functional decline of tissue stem cells and of mitochondrial dysfunction that adversely affect renewal and bioenergetic support in diverse tissues. Constructing a model of how telomeres, stem cells and mitochondria interact with key molecules governing genome integrity, 'stemness' and metabolism provides a framework for how diverse factors contribute to ageing and age-related disorders. C1 [Sahin, Erguen; DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Sahin, Erguen; DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dept Med & Genet,Dana Farber Canc Inst, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu FU National Institutes of Health [RO1CA84628, U01 CA84313]; US Department of Defense [W81XWH-08-1-0133]; Ellison Medical Foundation; Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science; Deutsche Forschungsgemeinschaft FX We thank L. Chin, N. Sharpless, S. Artandi, F. Muller, V. Walsh, S. Colla, M. Ugolotti, M. Jaskelioff, D. Liu and A.-J. Chen for discussions and critical reading of the manuscript. A. Protopopov and E. Ivanova kindly provided the chromosomal and telomere analysis in Fig. 2. We apologize to the members of the scientific community whose work could not be cited owing to space limitations. Grant support for our work was provided by National Institutes of Health grants RO1CA84628 and U01 CA84313, US Department of Defense grant W81XWH-08-1-0133, and the Ellison Medical Foundation. R. A. D. is an American Cancer Society Research Professor and is supported by the Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science. E. S. was supported by the Deutsche Forschungsgemeinschaft. NR 99 TC 312 Z9 325 U1 15 U2 104 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 25 PY 2010 VL 464 IS 7288 BP 520 EP 528 DI 10.1038/nature08982 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 574FL UT WOS:000275974200035 PM 20336134 ER PT J AU Gupta, RK Arany, Z Seale, P Mepani, RJ Ye, L Conroe, HM Roby, YA Kulaga, H Reed, RR Spiegelman, BM AF Gupta, Rana K. Arany, Zoltan Seale, Patrick Mepani, Rina J. Ye, Li Conroe, Heather M. Roby, Yang A. Kulaga, Heather Reed, Randall R. Spiegelman, Bruce M. TI Transcriptional control of preadipocyte determination by Zfp423 SO NATURE LA English DT Article ID PPAR-GAMMA; OLIGONUCLEOTIDE ARRAYS; CEREBELLAR DEVELOPMENT; ADIPOSE CONVERSION; ADIPOCYTE LINEAGE; GENE-EXPRESSION; IN-VIVO; CELLS; DIFFERENTIATION; ADIPOGENESIS AB The worldwide epidemic of obesity has increased the urgency to develop a deeper understanding of physiological systems related to energy balance and energy storage, including the mechanisms controlling the development of fat cells (adipocytes). The differentiation of committed preadipocytes to adipocytes is controlled by PPAR gamma and several other transcription factors(1), but the molecular basis for preadipocyte determination is not understood. Using a new method for the quantitative analysis of transcriptional components, we identified the zinc-finger protein Zfp423 as a factor enriched in preadipose versus non-preadipose fibroblasts. Ectopic expression of Zfp423 in non-adipogenic NIH 3T3 fibroblasts robustly activates expression of Pparg in undifferentiated cells and permits cells to undergo adipocyte differentiation under permissive conditions. Short hairpin RNA (shRNA)-mediated reduction of Zfp423 expression in 3T3-L1 cells blunts preadipocyte Pparg expression and diminishes the ability of these cells to differentiate. Furthermore, both brown and white adipocyte differentiation is markedly impaired in Zfp423-deficient mouse embryos. Zfp423 regulates Pparg expression, in part, through amplification of the BMP signalling pathway, an effect dependent on the SMAD-binding capacity of Zfp423. This study identifies Zfp423 as a transcriptional regulator of preadipocyte determination. C1 [Gupta, Rana K.; Arany, Zoltan; Seale, Patrick; Mepani, Rina J.; Ye, Li; Conroe, Heather M.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Gupta, Rana K.; Arany, Zoltan; Seale, Patrick; Mepani, Rina J.; Ye, Li; Conroe, Heather M.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Metab & Chron Dis, Boston, MA 02115 USA. [Gupta, Rana K.; Arany, Zoltan; Seale, Patrick; Mepani, Rina J.; Ye, Li; Conroe, Heather M.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Roby, Yang A.; Kulaga, Heather; Reed, Randall R.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Ctr Sensory Biol,Dept Mol Biol & Genet, Baltimore, MD 21205 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU Ruth Kirstein NRSA [F32 DK079507-01]; NHLBI [K08 HL79172-01]; Smith Family Foundation; NIH [DK081605, DK31405]; NIDCD [R01DC008295] FX We are grateful to S. Kleiner and S. Kajimura for critical reading of the manuscript and to all members of the Spiegelman laboratory for useful discussions. We thank B. Wagner for technical assistance in using robotic liquid handlers, B. Seed's laboratory for help with high-through query of Primer bank, and J. Brestelli for performing high-throughput queries of the Primer 3 program. We are also grateful to D. Bernlohr for the FABP4 antiserum. R. K. G. is supported by the Ruth Kirstein NRSA (F32 DK079507-01), Z. A. is supported by K08 HL79172-01 (NHLBI) and the Smith Family Foundation Grant, P. S. is supported by NIH DK081605, and the research described in this study was supported by NIH DK31405 to B. M. S. and by NIDCD R01DC008295 to R. R. R. NR 27 TC 174 Z9 179 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 25 PY 2010 VL 464 IS 7288 BP 619 EP U187 DI 10.1038/nature08816 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 574FL UT WOS:000275974200054 PM 20200519 ER PT J AU Ross, SE Mardinly, AR McCord, AE Zurawski, J Cohen, S Jung, C Hu, LD Mok, SI Shah, A Savner, EM Tolias, C Corfas, R Chen, SZ Inquimbert, P Xu, Y McInnes, RR Rice, FL Corfas, G Ma, QF Woolf, CJ Greenberg, ME AF Ross, Sarah E. Mardinly, Alan R. McCord, Alejandra E. Zurawski, Jonathan Cohen, Sonia Jung, Cynthia Hu, Linda Mok, Stephanie I. Shah, Anar Savner, Erin M. Tolias, Christos Corfas, Roman Chen, Suzhen Inquimbert, Perrine Xu, Yi McInnes, Roderick R. Rice, Frank L. Corfas, Gabriel Ma, Qiufu Woolf, Clifford J. Greenberg, Michael E. TI Loss of Inhibitory Interneurons in the Dorsal Spinal Cord and Elevated Itch in Bhlhb5 Mutant Mice SO NEURON LA English DT Article ID SPINOTHALAMIC TRACT NEURONS; PERIPHERAL-NERVE INJURY; PAIN HYPERSENSITIVITY; CENTRAL SENSITIZATION; GABAERGIC INHIBITION; SCRATCHING BEHAVIOR; FORMALIN TEST; HORN; RECEPTORS; RESPONSES AB Itch is the least well understood of all the somatic senses, and the neural circuits that underlie this sensation are poorly defined. Here we show that the atonal-related transcription factor Bhlhb5 is transiently expressed in the dorsal horn of the developing spinal cord and appears to play a role in the formation and regulation of pruritic (itch) circuits. Mice lacking Bhlhb5 develop self-inflicted skin lesions and show significantly enhanced scratching responses to pruritic agents. Through genetic fate-mapping and conditional ablation, we provide evidence that the pruritic phenotype in Bhlhb5 mutants is due to selective loss of a subset of inhibitory interneurons in the dorsal horn. Our findings suggest that Bhlhb5 is required for the survival of a specific population of inhibitory interneurons that regulate pruritis, and provide evidence that the loss of inhibitory synaptic input results in abnormal itch. C1 [Ross, Sarah E.; Mardinly, Alan R.; McCord, Alejandra E.; Zurawski, Jonathan; Cohen, Sonia; Hu, Linda; Mok, Stephanie I.; Shah, Anar; Savner, Erin M.; Tolias, Christos; Corfas, Roman; Ma, Qiufu; Woolf, Clifford J.; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Jung, Cynthia; McInnes, Roderick R.] Hosp Sick Children, Res Inst, Program Dev Biol, Toronto, ON M5G 1L7, Canada. [Jung, Cynthia; McInnes, Roderick R.] Hosp Sick Children, Res Inst, Genet Program, Toronto, ON M5G 1L7, Canada. [Cohen, Sonia; Inquimbert, Perrine; Corfas, Gabriel; Woolf, Clifford J.] Childrens Hosp, Dept Neurol, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Xu, Yi; Ma, Qiufu] Dana Farber Canc Inst, Boston, MA 02115 USA. [McInnes, Roderick R.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [McInnes, Roderick R.] Univ Toronto, Dept Pediat, Toronto, ON M5S 1A1, Canada. [McInnes, Roderick R.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. [Rice, Frank L.] Albany Med Coll, Ctr Neuropharmacol Neurosci, Albany, NY 12208 USA. [Rice, Frank L.] Integrated Tissue Dynam LL, Rensselaer, NY 12144 USA. RP Greenberg, ME (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. EM michael_greenberg@hms.harvard.edu OI Corfas, Roman/0000-0002-3096-6813 FU Jane Coffin Childs Fellowship; Dystonia Medical Research Foundation Fellowship; NIH [R01-NS-028829]; Developmental Disabilities Mental Retardation Research Center [NIH-P30-HD-18655] FX We thank E.C. Griffith for critical readings of the manuscript; D. Harmin for help with statistical analysis; M. Gee and P. Zhang for assistance with mouse colony management; the MRDDRC Gene Manipulation Core (M. Thompson, Y. Zhou, and H. Ye); the MRDDRC Imaging Core (L. Bu); and the MRDDRC Histology Core (M. Liana). This work was supported by a Jane Coffin Childs Fellowship and a Dystonia Medical Research Foundation Fellowship to S.E.R., NIH grant R01-NS-028829 to M.E.G., and the Developmental Disabilities Mental Retardation Research Center grant NIH-P30-HD-18655 for core support. NR 48 TC 141 Z9 144 U1 2 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 25 PY 2010 VL 65 IS 6 BP 886 EP 898 DI 10.1016/j.neuron.2010.02.025 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 576MP UT WOS:000276148900016 PM 20346763 ER PT J AU Ross, JS Normand, SLT Wang, Y Ko, DT Chen, J Drye, EE Keenan, PS Lichtman, JH Bueno, H Schreiner, GC Krumholz, HM AF Ross, Joseph S. Normand, Sharon-Lise T. Wang, Yun Ko, Dennis T. Chen, Jersey Drye, Elizabeth E. Keenan, Patricia S. Lichtman, Judith H. Bueno, Hector Schreiner, Geoffrey C. Krumholz, Harlan M. TI Hospital Volume and 30-Day Mortality for Three Common Medical Conditions SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE; QUALITY; MODEL; RATES; TIME AB BACKGROUND The association between hospital volume and the death rate for patients who are hospitalized for acute myocardial infarction, heart failure, or pneumonia remains unclear. It is also not known whether a volume threshold for such an association exists. METHODS We conducted cross-sectional analyses of data from Medicare administrative claims for all fee-for-service beneficiaries who were hospitalized between 2004 and 2006 in acute care hospitals in the United States for acute myocardial infarction, heart failure, or pneumonia. Using hierarchical logistic-regression models for each condition, we estimated the change in the odds of death within 30 days associated with an increase of 100 patients in the annual hospital volume. Analyses were adjusted for patients' risk factors and hospital characteristics. Bootstrapping procedures were used to estimate 95% confidence intervals to identify the condition-specific volume thresholds above which an increased volume was not associated with reduced mortality. RESULTS There were 734,972 hospitalizations for acute myocardial infarction in 4128 hospitals, 1,324,287 for heart failure in 4679 hospitals, and 1,418,252 for pneumonia in 4673 hospitals. An increased hospital volume was associated with reduced 30-day mortality for all conditions (P<0.001 for all comparisons). For each condition, the association between volume and outcome was attenuated as the hospital's volume increased. For acute myocardial infarction, once the annual volume reached 610 patients ( 95% confidence interval [CI], 539 to 679), an increase in the hospital volume by 100 patients was no longer significantly associated with reduced odds of death. The volume threshold was 500 patients ( 95% CI, 433 to 566) for heart failure and 210 patients ( 95% CI, 142 to 284) for pneumonia. CONCLUSIONS Admission to higher-volume hospitals was associated with a reduction in mortality for acute myocardial infarction, heart failure, and pneumonia, although there was a volume threshold above which an increased condition-specific hospital volume was no longer significantly associated with reduced mortality. C1 [Ross, Joseph S.] Mt Sinai Sch Med, New York, NY 10029 USA. [Ross, Joseph S.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Boston, MA USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wang, Yun; Chen, Jersey; Drye, Elizabeth E.; Schreiner, Geoffrey C.; Krumholz, Harlan M.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Wang, Yun; Chen, Jersey; Lichtman, Judith H.; Krumholz, Harlan M.] Yale Univ, Sch Med, New Haven, CT USA. [Ko, Dennis T.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Ko, Dennis T.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Bueno, Hector] Hosp Gen Univ Gregorio Maranon, Madrid, Spain. RP Ross, JS (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM joseph.ross@mssm.edu RI Max, Mad/E-5238-2010; BUENO, HECTOR/I-3910-2015; OI Max, Mad/0000-0001-6966-6829; BUENO, HECTOR/0000-0003-0277-7596; Ko, Dennis/0000-0001-6840-8051 FU CMS [HHSM-500-2005-CO001C]; National Institute on Aging [K08 AG032886]; American Federation for Aging Research; Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Madrid [BA08/90010] FX Supported by a contract (HHSM-500-2005-CO001C) with the CMS, by a grant (K08 AG032886, to Dr. Ross) from the National Institute on Aging, by the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program, and by a grant (BA08/90010, to Dr. Bueno) from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Madrid. NR 22 TC 125 Z9 128 U1 1 U2 15 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 25 PY 2010 VL 362 IS 12 BP 1110 EP 1118 DI 10.1056/NEJMsa0907130 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 573FU UT WOS:000275894600008 PM 20335587 ER PT J AU Pless, ML Chen, YB Copen, WA Frosch, MP AF Pless, Misha L. Chen, Yi-Bin Copen, William A. Frosch, Matthew P. TI A Woman with Paresthesias and Ataxia Intravascular large-B-cell lymphoma. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; ANTHRACYCLINE-BASED CHEMOTHERAPY; HIGH-DOSE CHEMOTHERAPY; PRIMARY CNS LYMPHOMA; MATRIX METALLOPROTEINASES; ADHESION MOLECULES; MULTIPLE-SCLEROSIS; 1ST-LINE TREATMENT; TRANSPLANTATION; RADIOTHERAPY C1 [Pless, Misha L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Chen, Yi-Bin] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Copen, William A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pless, Misha L.] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Chen, Yi-Bin] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Copen, William A.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Frosch, Matthew P.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Pless, ML (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU Bayer; EMD Serono; Pfizer; Teva Neuroscience; Novartis; Elsevier FX Dr. Pless reports receiving consulting fees from Bayer, EMD Serono, Pfizer, and Teva Neuroscience; honoraria from Bayer, EMD Serono, Novartis, Pfizer, and Teva Neuroscience; and grant support from EMD Serono; and Dr. Frosch, receiving honoraria from Elsevier. No other potential conflict of interest relevant to this article was reported. NR 30 TC 2 Z9 2 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 MAR 25 PY 2010 VL 362 IS 12 BP 1129 EP 1138 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 573FU UT WOS:000275894600012 PM 20335590 ER PT J AU Kathiresan, S AF Kathiresan, Sekar TI Genetic Variants in Lp(a) Lipoprotein and Coronary Disease REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 25 PY 2010 VL 362 IS 12 BP 1147 EP 1148 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 573FU UT WOS:000275894600019 ER PT J AU Wilber, ST Sullivan, AF Camargo, CA AF Wilber, Scott T. Sullivan, Ashley F. Camargo, Carlos A., Jr. TI Chronic Pain and Risk of Falls in Older Adults SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID VITAMIN-D C1 [Wilber, Scott T.] Summa Akron City Hosp, Akron, OH USA. [Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wilber, ST (reprint author), Summa Akron City Hosp, Akron, OH USA. EM wilbers@summa-health.org NR 5 TC 0 Z9 0 U1 0 U2 0 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 MAR 24 PY 2010 VL 303 IS 12 BP 1148 EP 1148 DI 10.1001/jama.2010.324 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 573AC UT WOS:000275879600015 PM 20332398 ER PT J AU Hung, AY Sung, CC Brito, IL Sheng, M AF Hung, Albert Y. Sung, Clifford C. Brito, Ilana L. Sheng, Morgan TI Degradation of Postsynaptic Scaffold GKAP and Regulation of Dendritic Spine Morphology by the TRIM3 Ubiquitin Ligase in Rat Hippocampal Neurons SO PLOS ONE LA English DT Article ID RING FINGER PROTEIN; EXCITATORY SYNAPSES; SYNAPTIC PROTEIN; DIFFERENTIAL EXPRESSION; PROTEASOME SYSTEM; DENSITY PROTEINS; SHANK FAMILY; MYOSIN-V; COMPLEX; PSD-95 AB Changes in neuronal activity modify the structure of dendritic spines and alter the function and protein composition of synapses. Regulated degradation of postsynaptic density (PSD) proteins by the ubiquitin-proteasome system is believed to play an important role in activity-dependent synaptic remodeling. Stimulating neuronal activity in vitro and in vivo induces the ubiquitination and degradation of GKAP/SAPAP and Shank, major scaffold proteins of the PSD. However, the specific ubiquitin ligases that regulate postsynaptic protein composition have not been identified. Here we identify the RING finger-containing protein TRIM3 as a specific E3 ubiquitin ligase for the PSD scaffold GKAP/SAPAP1. Present in PSD fractions from rat brain, TRIM3 stimulates ubiquitination and proteasome-dependent degradation of GKAP, and induces the loss of GKAP and associated scaffold Shank1 from postsynaptic sites. Suppression of endogenous TRIM3 by RNA interference (RNAi) results in increased accumulation of GKAP and Shank1 at synapses, as well as enlargement of dendritic spine heads. RNAi of TRIM3 also prevented the loss of GKAP induced by synaptic activity. Thus, TRIM3 is a novel E3 ligase that mediates activity-dependent turnover of PSD scaffold proteins and is a negative regulator of dendritic spine morphology. C1 [Hung, Albert Y.; Sung, Clifford C.; Brito, Ilana L.; Sheng, Morgan] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Hung, Albert Y.; Sung, Clifford C.; Brito, Ilana L.; Sheng, Morgan] MIT, Dept Biol, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Hung, Albert Y.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Hung, AY (reprint author), MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, E25-618, Cambridge, MA 02139 USA. EM msheng@mit.edu FU National Institutes of Health [K08 Award NS41411] FX The work was funded by National Institutes of Health K08 Award NS41411 (A. Y. H.). M. S. was an Investigator of the Howard Hughes Medical Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 57 Z9 57 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 MAR 24 PY 2010 VL 5 IS 3 AR e9842 DI 10.1371/journal.pone.0009842 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 573FT UT WOS:000275894500011 PM 20352094 ER PT J AU Ix, JH de Boer, IH Wassel, CL Criqui, MH Shlipak, MG Whooley, MA AF Ix, Joachim H. de Boer, Ian H. Wassel, Christina L. Criqui, Michael H. Shlipak, Michael G. Whooley, Mary A. TI Urinary Creatinine Excretion Rate and Mortality in Persons With Coronary Artery Disease The Heart and Soul Study SO CIRCULATION LA English DT Article DE cardiovascular diseases; creatinine; muscles; mortality ID CARDIOVASCULAR-DISEASE; MUSCLE MASS; CYSTATIN-C; RESISTANCE EXERCISE; CLINICAL-CARDIOLOGY; SEDENTARY MEN; ASSOCIATION; INDIVIDUALS; METABOLISM; VARIABILITY AB Background-In persons with coronary artery disease, low body mass index is associated with greater mortality; however, it is uncertain whether low muscle mass is a risk factor for mortality in this setting. Methods and Results-In this study, 903 individuals with coronary artery disease provided 24-hour urine collections. We measured urine creatinine and volume and calculated creatinine excretion rate, a marker of muscle mass. Cox proportional-hazards models evaluated the association of creatinine excretion rate with mortality risk. Over a median follow-up of 6.0 years, 232 participants (26%) died. Compared with the highest sex-specific creatinine excretion rate tertile, the lowest tertile (<1068 mg/d in men, <766 mg/d in women) was associated with >2-fold risk of mortality (hazard ratio, 2.30; 95% confidence interval, 1.51 to 3.51) in models adjusted for age, sex, race, cystatin C-based estimated glomerular filtration rate, body mass index, traditional cardiovascular disease risk factors, and C-reactive protein levels. The association was essentially unaltered with further adjustment for physical fitness, left ventricular mass, left ventricular ejection fraction, or fasting insulin and glucose levels. Conclusions-Lower creatinine excretion rate is strongly associated with mortality in outpatients with coronary artery disease, independently of conventional measures of body composition, kidney function, and traditional coronary artery disease risk factors. Future studies should determine whether low creatinine excretion rate may be a modifiable risk factor for mortality among persons with coronary artery disease, potentially through resistive exercise training or nutrition interventions. (Circulation. 2010; 121: 1295-1303.) C1 [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92161 USA. [Ix, Joachim H.; Wassel, Christina L.; Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92161 USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Med, Div Cardiol, San Diego, CA 92161 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA 92161 USA. [de Boer, Ian H.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [de Boer, Ian H.] Univ Washington, Dept Med, Kidney Res Inst, Seattle, WA USA. [Shlipak, Michael G.; Whooley, Mary A.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Shlipak, Michael G.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shlipak, Michael G.; Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu FU American Heart Association; National Heart Lung and Blood Institute (NHLBI) [R01HL096851, R01 HL079235]; Department of Veterans Epidemiology; Department of Veterans Affairs Health Services Research and Development service; American Federation for Aging Research; Robert Wood Johnson Foundation; Ischemia Research and Education Foundation; American Diabetes Association; National Institutes on Aging; National Institutes on Diabetes Digestive and Kidney Diseases; Department of Defense FX This study was supported by grants from the American Heart Association (Fellow-to-Faculty Transition) and the National Heart Lung and Blood Institute (NHLBI: R01HL096851) to Dr Ix. The Heart and Soul Study was supported by the Department of Veterans Epidemiology Merit Review Program, the Department of Veterans Affairs Health Services Research and Development service, the NHLBI (R01 HL079235), the American Federation for Aging Research (Paul Beeson Scholars Program), the Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), and the Ischemia Research and Education Foundation. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.; Dr Ix reports receiving grant support from the NHLBI, the American Heart Association, and the American Diabetes Association. Drs Wassel and Criqui report receiving grants from the NHLBI. Dr Shlipak reports receiving grant support from the American Heart Association, NHLBI, National Institutes on Aging, and National Institutes on Diabetes Digestive and Kidney Diseases. Dr Whooley reports receiving grants from the NHLBI, Veterans Affairs, and Department of Defense. Dr de Boer reports no conflicts. NR 33 TC 52 Z9 53 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 23 PY 2010 VL 121 IS 11 BP 1295 EP 1303 DI 10.1161/CIRCULATIONAHA.109.924266 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 572VW UT WOS:000275863200005 PM 20212276 ER PT J AU Shah, RV Januzzi, JL AF Shah, Ravi V. Januzzi, James L., Jr. TI ST-Elevation Alternans and Nonsustained Polymorphic Ventricular Tachycardia in a Patient With Prinzmetal (Variant) Angina SO CIRCULATION LA English DT Editorial Material ID SEGMENT C1 [Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 5 TC 1 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 23 PY 2010 VL 121 IS 11 BP 1371 EP 1373 DI 10.1161/CIR.0b013e3181d8d759 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 572VW UT WOS:000275863200014 PM 20308628 ER PT J AU Drachman, DE AF Drachman, Douglas E. TI Response to Letter Regarding Article, "Drug-Eluting Stents in Animals and Patients: Where Do We Stand Today?" SO CIRCULATION LA English DT Letter C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Drachman, DE (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 23 PY 2010 VL 121 IS 11 BP E247 EP E247 DI 10.1161/CIR.0b013e3181d8723a PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 572VW UT WOS:000275863200017 ER PT J AU Morrow, DA Scirica, BM Sabatine, MS de Lemos, JA Murphy, SA Jarolim, P Theroux, P Bode, C Braunwald, E AF Morrow, David A. Scirica, Benjamin M. Sabatine, Marc S. de Lemos, James A. Murphy, Sabina A. Jarolim, Petr Theroux, Pierre Bode, Christophe Braunwald, Eugene TI B-Type Natriuretic Peptide and the Effect of Ranolazine in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Observations From the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE angina; myocardial infarction; natriuretic peptides; ranolazine; unstable angina ID LEFT-VENTRICULAR FUNCTION; CHRONIC HEART-FAILURE; ARTERY-DISEASE; PROGNOSTIC VALUE; TROPONIN-T; RISK; MORTALITY; OXIDATION; ANGINA; MYOCYTES AB Objectives We designed a prospective evaluation of the interaction between B-type natriuretic peptide (BNP) and the effect of ranolazine in patients with acute coronary syndromes (ACS) as part of a randomized, blinded, placebo-controlled trial. Background Ranolazine is believed to exert anti-ischemic effects by reducing myocardial sodium and calcium overload and consequently ventricular wall stress. BNP increases in response to increased wall stress and is a strong risk indicator in ACS. Methods We measured plasma BNP in all available baseline samples (n = 4,543) among patients with non-ST-segment elevation ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial and followed them for a mean of 343 days. The primary end point was a composite of cardiovascular death, myocardial infarction, and recurrent ischemia. BNP elevation was defined as >80 pg/ml. Results Patients with elevated BNP (n = 1,935) were at significantly higher risk of the primary trial end point (26.4% vs. 20.4%, p < 0.0001), cardiovascular death (8.0% vs. 2.1%, p < 0.001), and myocardial infarction (10.6% vs. 5.8%, p < 0.001) at 1 year. In patients with BNP > 80 pg/ml, ranolazine reduced the primary end point (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.66 to 0.94, p = 0.009). The effect of ranolazine in patients with BNP > 80 pg/ml was directionally similar for recurrent ischemia (HR: 0.78; 95% CI: 0.62 to 0.98; p = 0.04) and cardiovascular death or myocardial infarction (HR: 0.83; 95% CI: 0.66 to 1.05, p = 0.12). There was no detectable effect in those with low BNP (p interaction value = 0.05). Conclusions Our findings indicate that ranolazine may have enhanced efficacy in high-risk patients with ACS identified by increased BNP. The interaction of biomarkers of hemodynamic stress and the effects of ranolazine warrants additional investigation. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes; NCT00099788) (J Am Coll Cardiol 2010; 55: 1189-96) (C) 2010 by the American College of Cardiology Foundation C1 [Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Morrow, David A.; Scirica, Benjamin M.; Sabatine, Marc S.; Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Jarolim, Petr] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Jarolim, Petr] Harvard Univ, Sch Med, Boston, MA USA. [de Lemos, James A.] Univ Texas Southwestern Med Sch, Dallas, TX USA. [Theroux, Pierre] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Bode, Christophe] Univ Freiburg, Med Univ Klin, Freiburg, Germany. RP Morrow, DA (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org FU CV Therapeutics (Palo Alto, California); Accumetrics; Amgen; AstraZeneca; Bayer Healthcare; Beckman-Coulter; Biosite; Bristol-Myers Squibb; CV Therapeutics; Daiichi Sankyo; Eisai Medical Research; Eli Lilly and Co.; Genentech; GlaxoSmithKline; Integrated Therapeutics; Johnson Johnson; Merck and Company; Millennium Pharmaceuticals; Nanosphere; Novartis Pharmaceuticals; Nuvelo; Ortho-Clinical Diagnostics,; Pfizer; Roche Diagnostics; Sanofi-Aventis; Sanofi-Synthelabo; Schering-Plough; Siemens; Singulex; CVT/Gilead; OrthoClinical Diagnostics FX The MERLIN-TIMI 36 trial was supported by CV Therapeutics (Palo Alto, California).; The TIMI Study Group has received significant research grant support from Accumetrics, Amgen, AstraZeneca, Bayer Healthcare, Beckman-Coulter, Biosite, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo, Eisai Medical Research, Eli Lilly and Co., Genentech, GlaxoSmithKline, Integrated Therapeutics, Johnson & Johnson, Merck and Company, Millennium Pharmaceuticals, Nanosphere, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Sanofi-Synthelabo, Schering-Plough, Siemens, and Singulex. Dr. Morrow has received honoraria for educational presentations from CV Therapeutics, Eli Lilly, and Sanofi-Aventis; served as a consultant for Beckman Coulter, Critical Diagnostics, CV Therapeutics, Sanofi-Aventis, Schering Plough, and Siemens; and is a paid member of a Clinical Events Committed for AstraZeneca. Dr. Scirica is a consultant for, educational presenter for, and has received research support from CVT/Gilead, and has received research support from Roche Diagnostics. Dr. Sabatine has received research support from CV Therapeutics and OrthoClinical Diagnostics. Dr. de Lemos has received grant support and consulting income from Biosite and Roche Diagnostics. Dr. Jarolim has received research support from Amgen, Beckman-Coulter, OrthoClinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics; and honoraria for educational presentations from OrthoClinical Diagnostics. Dr. Braunwald is the Chairman of the TIMI Study Group at the Brigham and Women's Hospital. Dr. Braunwald has received honorarium from Bayer AG, CV Therapeutics, Daiichi Sankyo, Eli Lilly, Merck & Co., Momenta, Schering-Plough, Sanofi-Aventis, Cytokinetics, Genzyme, GlaxoSmithKline, and Broadview Ventures. NR 34 TC 31 Z9 32 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 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 23 PY 2010 VL 55 IS 12 BP 1189 EP 1196 DI 10.1016/j.jacc.2009.09.068 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 570HK UT WOS:000275663200003 PM 20298924 ER PT J AU Cho, JM Raffel, OC Stone, JR Kim, CJ Jang, IK AF Cho, Jin-Man Raffel, Owen C. Stone, James R. Kim, Chong-Jin Jang, Ik-Kyung TI Spontaneous Recanalization of a Coronary Artery After Thrombotic Occlusion In Vivo Demonstration With Optical Coherence Tomography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material C1 [Cho, Jin-Man; Kim, Chong-Jin] Kyung Hee Univ, E W Neo Med Ctr, Seoul, South Korea. [Raffel, Owen C.; Stone, James R.; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Cho, JM (reprint author), Kyung Hee Univ, E W Neo Med Ctr, Seoul, South Korea. NR 0 TC 10 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 23 PY 2010 VL 55 IS 12 BP 1274 EP 1274 DI 10.1016/j.jacc.2008.11.071 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 570HK UT WOS:000275663200015 PM 20298935 ER PT J AU Cudkowicz, ME Swash, M AF Cudkowicz, Merit E. Swash, Michael TI CSF markers in amyotrophic lateral sclerosis Has the time come? SO NEUROLOGY LA English DT Editorial Material ID BIOMARKERS C1 [Swash, Michael] Queen Mary Univ London, Royal London Hosp, Dept Neurol, London E1 1BB, England. [Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Swash, M (reprint author), Queen Mary Univ London, Royal London Hosp, Dept Neurol, London E1 1BB, England. EM mswash@btinternet.com OI Swash, Michael/0000-0002-8717-8914 NR 4 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 23 PY 2010 VL 74 IS 12 BP 949 EP 950 DI 10.1212/WNL.0b013e3181d72c31 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 577WD UT WOS:000276253800004 PM 20308678 ER PT J AU Fernandes, F Ansari, IUH Striker, R AF Fernandes, Fiona Ansari, Israr-ul H. Striker, Rob TI Cyclosporine Inhibits a Direct Interaction between Cyclophilins and Hepatitis C NS5A SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO; RNA-POLYMERASE; CELL-CULTURE; REPLICATION; PROTEIN; GENOME; BINDING; STRAIN; DOMAIN AB Background: Hepatitis C Virus (HCV) infection is a leading indication for liver transplantation. HCV infection reoccurs almost universally post transplant, decreasing both graft longevity and patient survival. The immunosuppressant, cyclosporine A (CsA) has potent anti-HCV activity towards both HCV replicons and the genotype 2a cell culture infectious virus. Previously, we isolated mutations in the 1bN replicon with less sensitivity to CsA that mapped to both NS5A and NS5B regions of the virus. Mutations in NS5A alone conferred decreased CsA susceptibility regardless of NS5B mutations. Methodology/Principal Findings: We examined the mechanisms by which NS5A mutations contribute to CsA resistance and if they are strain dependent. Using in vitro mutagenesis, the amino acid position 321 mutation of NS5A was restored to the wild-type tyrosine residue conferring partial CsA susceptibility on the mutant replicon. The 321 mutation also alters CsA susceptibility of the JFH cell culture virus. Additionally, we demonstrated a novel CsA-sensitive interaction between NS5A and both cyclophilin A and B. Both the mutant NS5A and wild type NS5A bind cyclophilin in vitro. The NS5A: cyclophilin interaction requires both the NS5A region identified by the resistance mutants and cyclophilin catalytic residues. In cell culture, NS5A from CsA resistant mutant has an enhanced interaction with cyclophilin B. Additionally; NS5B facilitates a stronger binding of mutant NS5A to endogenous cyclophilin B than wild-type in cell culture. Conclusions/Significance: Collectively, this data suggests direct interactions between cyclophilins and NS5A are critical to understand for optimal use of cyclophilin inhibitors in anti-HCV therapy. C1 [Fernandes, Fiona; Ansari, Israr-ul H.; Striker, Rob] Univ Wisconsin, Dept Med, Madison, WI USA. [Striker, Rob] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. RP Fernandes, F (reprint author), SUNY Stony Brook, Dept Microbiol & Mol Genet, Stony Brook, NY 11794 USA. EM tstriker@wisc.edu FU American Cancer Society Research Scholar [07-077-01]; Office of Research and Development; Biomedical Laboratory R&D Service, Department of Veterans Affairs; University of Wisconsin Institute for Clinical and Translational Research; NIH Clinical and Translational Science [1UL1RR025011] FX This research was supported by the American Cancer Society Research Scholar Grant (07-077-01) to R. S., by the Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs, and by the University of Wisconsin Institute for Clinical and Translational Research, funded through an NIH Clinical and Translational Science Award, grant number 1UL1RR025011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 57 Z9 57 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 MAR 23 PY 2010 VL 5 IS 3 AR e9815 DI 10.1371/journal.pone.0009815 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 573FS UT WOS:000275894400017 PM 20352119 ER PT J AU Beerman, I Bhattacharya, D Zandi, S Sigvardsson, M Weissman, IL Bryder, D Rossi, DJ AF Beerman, Isabel Bhattacharya, Deepta Zandi, Sasan Sigvardsson, Mikael Weissman, Irving L. Bryder, David Rossi, Derrick J. TI Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HSCs; leukemia; lineage specification ID COMPARTMENT AB Aging of the hematopoietic stem cell compartment is believed to contribute to the onset of a variety of age-dependent blood cell pathophysiologies. Mechanistic drivers of hematopoietic stem cell (HSC) aging include DNA damage accumulation and induction of tumor suppressor pathways that combine to reduce the regenerative capacity of aged HSCs. Such mechanisms do not however account for the change in lymphoid and myeloid lineage potential characteristic of HSC aging, which is believed to be central to the decline of immune competence and predisposition to myelogenous diseases in the elderly. Here we have prospectively isolated functionally distinct HSC clonal subtypes, based on cell surface phenotype, bearing intrinsically different capacities to differentiate toward lymphoid and myeloid effector cells mediated by quantitative differences in lineage priming. Finally, we present data supporting a model in which clonal expansion of a class of intrinsically myeloid-biased HSCs with robust self-renewal potential is a central component of hematopoietic aging. C1 [Weissman, Irving L.] Stanford Univ, Ctr Canc, Stanford Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Beerman, Isabel; Rossi, Derrick J.] Childrens Hosp Boston, Harvard Stem Cell Inst, Program Cellular & Mol Med, Immune Dis Inst, Boston, MA 02115 USA. [Beerman, Isabel; Rossi, Derrick J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Bhattacharya, Deepta] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Zandi, Sasan; Sigvardsson, Mikael] Linkoping Univ, Dept Biomed & Surg, Linkoping, Sweden. [Weissman, Irving L.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Bryder, David] Lund Univ, Immunol Unit, Inst Expt Med Sci, Lund, Sweden. RP Weissman, IL (reprint author), Stanford Univ, Ctr Canc, Stanford Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. EM irv@stanford.edu; david.bryder@med.lu.se; rossi@idi.harvard.edu OI Sigvardsson, Mikael/0000-0001-8527-7276 FU Swedish Medical Research Council; Swedish Strategic Research Foundation; Swedish Cancer Society; Crafoord foundation; Medical Faculty at Lund University; National Institutes of Aging; Harvard Stem Cell Institute FX D. B. is supported by the Swedish Medical Research Council, the Swedish Strategic Research Foundation, the Swedish Cancer Society, the Crafoord foundation, and the Medical Faculty at Lund University. D. J. R. is supported by grants from the National Institutes of Aging and the Harvard Stem Cell Institute. NR 18 TC 214 Z9 217 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 MAR 23 PY 2010 VL 107 IS 12 BP 5465 EP 5470 DI 10.1073/pnas.1000834107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 573GY UT WOS:000275898300037 PM 20304793 ER PT J AU Fishman, J Ten Have, T Casarett, D AF Fishman, Jessica Ten Have, Thomas Casarett, David TI Cancer and the Media How Does the News Report on Treatment and Outcomes? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID BREAST-CANCER; NURSING-HOMES; CARE; COVERAGE; LIFE; DEATH; PAIN; END; CREDIBILITY; MANAGEMENT AB Background: Cancer receives a great deal of news media attention. Although approximately half of all US patients with cancer die of their illness or of related complications, it is unknown whether reports in the news media reflect this reality. Methods: To determine how cancer news coverage repot-is about cancer care and outcornes, we conducted a content analysis of US cancer news reporting in 8 large-readership newspapers and 5 national magazines. Trained coders determined the proportion of articles reporting about cancer survival, cancer death and dying, aggressive cancer treatment, cancer treatment failure, adverse events of cancer treatment, and end-of-life palliative or hospice care. Results: Of 436 articles about cancer, 140 (32.1%; 95% confidence interval [CI], 28%-37%) focused Oil survival and only 33 (7.6 %; 5%-.1.0%) focused on death and dying (p<.001, chi(2) test). Only 57 articles (13.1%; 10%-17%) reported that aggressive cancer treatments can fail, and 131. (30.0%; 26%-35%) reported that aggressive treatments can result in adverse events. Although most articles (249 of 436 [57.1%]; 95% CI, 52%-62%) discussed aggressive treatments exclusively, almost none (2 of 436; [0.5%]; 0%-2%) discussed end-of-life palliative or hospice care exclusively (P <.001, chi(2) test), and only a few (11 of 436 [2.5%]; 1%-6%) discussed aggressive treatment, and end-of-life care. Conclusions: News reports about cancer frequently discuss aggressive treatment and survival but rarely discuss treatment failure, adverse events, end-of-life care, or death. These portrayals of cancer care in the news media may give patients an inappropriately optimistic view of cancer treatment, outcomes, and prognosis. C1 [Fishman, Jessica; Ten Have, Thomas] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Fishman, Jessica] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. [Casarett, David] Univ Penn, VA Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Casarett, David] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Fishman, Jessica; Ten Have, Thomas; Casarett, David] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Fishman, J (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, 711 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM fishman1@mail.med.upenn.edu FU NCI NIH HHS [5P50CA095856-05, P20 CA095856] NR 49 TC 16 Z9 16 U1 1 U2 10 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 MAR 22 PY 2010 VL 170 IS 6 BP 515 EP 518 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 571QB UT WOS:000275768400002 PM 20233800 ER PT J AU Lobb, R Allen, JD Emmons, KM Ayanian, JZ AF Lobb, Rebecca Allen, Jennifer D. Emmons, Karen M. Ayanian, John Z. TI Timely Care After an Abnormal Mammogram Among Low-Income Women in a Public Breast Cancer Screening Program SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PATIENT NAVIGATION; FOLLOW-UP; NATIONAL BREAST; RETROSPECTIVE ANALYSIS; SOCIOECONOMIC-STATUS; SOCIAL DETERMINANTS; UNDERSERVED WOMEN; HEALTH-INSURANCE; URBAN-POPULATION; UNITED-STATES AB Background: Since 1990, the National Breast and Cervical Cancer Early Detection Program (BCCEDP) has funded breast cancer screening and diagnostic services for low-income, underinsured women. Case management was implemented in 2001 to address barriers to follow-up after an abnormal mammogram, and free treatment was introduced in 2004. However, the effect of these policies on timeliness of care has not been empirically evaluated. Methods: Among 2252 BCCEDP participants in Massachusetts during 1998 through 2007, we conducted a time-to-event analysis with prepolicy-postpolicy comparisons to examine associations of case management and free treatment with diagnostic and treatment delays (>60 days and >90 days, respectively) after an abnormal mammogram. Results: The proportion of women experiencing a diagnostic delay decreased from 33% to 23% after the introduction of case management (P<.001), with a significant reduction in the adjusted risk of diagnostic delay (relative risk [RR], 0.65; 95% confidence interval [CI], 0.53-0.79) that did not differ by race and ethnicity. However, case management was not associated with changes in treatment delay (RR, 0.93; 95% CI, 0.80-1.10). Free treatment was not associated with changes in the adjusted risk of diagnostic delay (RR, 0.61; 95% CI, 0.331.14) or treatment delay (RR, 0.77; 95% CI, 0.43-1.38) beyond improvements associated with case management. Conclusions: Case management to assist women in overcoming logistic and psychosocial barriers to care may improve time to diagnosis among low-income women who receive free breast cancer screening and diagnostic services. Programs that provide services to coordinate care, in addition to free screening and diagnostic tests, may improve population health. C1 [Lobb, Rebecca] St Michaels Hosp, Ctr Res Inner City Hlth, Toronto, ON M5B 1W8, Canada. [Ayanian, John Z.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Ayanian, John Z.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Allen, Jennifer D.; Emmons, Karen M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lobb, Rebecca; Allen, Jennifer D.; Emmons, Karen M.; Ayanian, John Z.] Harvard Univ, Sch Med, Sch Publ Hlth, Boston, MA 02115 USA. RP Lobb, R (reprint author), St Michaels Hosp, Ctr Res Inner City Hlth, 30 Bond St, Toronto, ON M5B 1W8, Canada. EM lobbr@smh.toronto.on.ca RI Allen, Jennifer/M-2113-2015; OI Lobb, Rebecca/0000-0003-3503-0675 FU NCI NIH HHS [R25 CA057711-15, U01 CA114644-04, R25 CA057711, U01 CA114644, 5 R25 CA057711-15, K05 CA124415-02, 5 U01 CA114644, K05CA124415, K05 CA124415]; NCRR NIH HHS [1 UL1 RR 025758-01, UL1 RR025758-01, UL1 RR025758] NR 38 TC 20 Z9 21 U1 3 U2 10 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 MAR 22 PY 2010 VL 170 IS 6 BP 521 EP 528 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 571QB UT WOS:000275768400004 PM 20233801 ER PT J AU Dockendorff, C Buhrlage, S Weiwer, M Kim, HJ Ting, A Nag, P Germain, A Johnston, S Doud, K Koehler, A Mandinova, A Scherer, C MacPherson, L AF Dockendorff, Chris Buhrlage, Sara Weiwer, Michel Kim, Han-Je Ting, Amal Nag, Partha Germain, Andrew Johnston, Stephen Doud, Katie Koehler, Angela Mandinova, Anna Scherer, Christina MacPherson, Lawrence TI Identification of novel macrocycles as potent inhibitors of the hedgehog signaling pathway SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Broad Inst, Dept Med Chem & Probe Dev, Cambridge, MA USA. Broad Inst, Dept Analyt Chem, Cambridge, MA USA. Broad Inst, Dept Ligand Discovery, Cambridge, MA USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 367-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189303493 ER PT J AU Gray, NS AF Gray, Nathanael S. TI Screening and rational design approaches for developing selective protein kinase inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Gray, Nathanael S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 21-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189300404 ER PT J AU Greytak, AB McLaurin, EJ Curtin, PN Liu, WH Martin, JD Lanning, RM Jain, RK Bawendi, MG Nocera, DG AF Greytak, Andrew B. McLaurin, Emily J. Curtin, Peter N. Liu, Wenhao Martin, John D. Lanning, Ryan M. Jain, Rakesh K. Bawendi, Moungi G. Nocera, Daniel G. TI Smart quantum dot sensing SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MIT, Dept Chem, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 177-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189303075 ER PT J AU Huang, HC Yang, YS Koria, P Rege, K AF Huang, Huang-Chiao Yang, Yoonsun Koria, Piyush Rege, Kaushal TI Degradable polypeptide-nanoparticle matrices for combined photothermal ablation and drug delivery SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Arizona State Univ, Biol Design Program, Tempe, AZ USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 561-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189300669 ER PT J AU Holmes, MD Chen, WY Li, L Hertzmark, E Spiegelman, D Hankinson, SE AF Holmes, Michelle D. Chen, Wendy Y. Li, Lisa Hertzmark, Ellen Spiegelman, Donna Hankinson, Susan E. TI Aspirin Intake and Survival After Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MARGINAL STRUCTURAL MODELS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-DOSE ASPIRIN; NSAID USE; POSTMENOPAUSAL WOMEN; PRIMARY PREVENTION; RISK; COHORT; METAANALYSIS; RECURRENCE AB Purpose Animal and in vitro studies suggest that aspirin may inhibit breast cancer metastasis. We studied whether aspirin use among women with breast cancer decreased their risk of death from breast cancer. Methods This was a prospective observational study based on responses from 4,164 female registered nurses in the Nurses' Health Study who were diagnosed with stages I, II, or III breast cancer between 1976 and 2002 and were observed until death or June 2006, whichever came first. The main outcome was breast cancer mortality risk according to number of days per week of aspirin use (0, 1, 2 to 5, or 6 to 7 days) first assessed at least 12 months after diagnosis and updated. Results There were 341 breast cancer deaths. Aspirin use was associated with a decreased risk of breast cancer death. The adjusted relative risks (RRs) for 1, 2 to 5, and 6 to 7 days of aspirin use per week compared with no use were 1.07 (95% CI, 0.70 to 1.63), 0.29 (95% CI, 0.16 to 0.52), and 0.36 (95% CI, 0.24 to 0.54), respectively (test for linear trend, P < .001). This association did not differ appreciably by stage, menopausal status, body mass index, or estrogen receptor status. Results were similar for distant recurrence. The adjusted RRs were 0.91 (95% CI, 0.62 to 1.33), 0.40 (95% CI, 0.24 to 0.65), and 0.57 (95% CI, 0.39 to 0.82; test for trend, P = .03) for 1, 2 to 5, and 6 to 7 days of aspirin use, respectively. Conclusion Among women living at least 1 year after a breast cancer diagnosis, aspirin use was associated with a decreased risk of distant recurrence and breast cancer death. C1 [Holmes, Michelle D.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Holmes, MD (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM michelle.holmes@channing.harvard.edu FU National Institutes of Health [CA87969] FX Supported by National Institutes of Health Grant No. CA87969. NR 40 TC 164 Z9 167 U1 2 U2 14 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 MAR 20 PY 2010 VL 28 IS 9 BP 1467 EP 1472 DI 10.1200/JCO.2009.22.7918 PG 6 WC Oncology SC Oncology GA 572IR UT WOS:000275824600006 PM 20159825 ER PT J AU Ryan, CJ Smith, MR Fong, L Rosenberg, JE Kantoff, P Raynaud, F Martins, V Lee, G Kheoh, T Kim, J Molina, A Small, EJ AF Ryan, Charles J. Smith, Matthew R. Fong, Lawrence Rosenberg, Jonathan E. Kantoff, Philip Raynaud, Florence Martins, Vanessa Lee, Gloria Kheoh, Thian Kim, Jennifer Molina, Arturo Small, Eric J. TI Phase I Clinical Trial of the CYP17 Inhibitor Abiraterone Acetate Demonstrating Clinical Activity in Patients With Castration-Resistant Prostate Cancer Who Received Prior Ketoconazole Therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MITOXANTRONE PLUS PREDNISONE; ANTIANDROGEN WITHDRAWAL; MECHANISMS; DOCETAXEL; GUIDELINES; EXPRESSION; CARCINOMA; GENES AB Purpose Abiraterone acetate is a prodrug of abiraterone, a selective inhibitor of CYP17, the enzyme catalyst for two essential steps in androgen biosynthesis. In castration-resistant prostate cancers (CRPCs), extragonadal androgen sources may sustain tumor growth despite a castrate environment. This phase I dose-escalation study of abiraterone acetate evaluated safety, pharmacokinetics, and effects on steroidogenesis and prostate-specific antigen (PSA) levels in men with CPRC with or without prior ketoconazole therapy. Patients and Methods Thirty-three men with chemotherapy-naive progressive CRPC were enrolled. Nineteen patients (58%) had previously received ketoconazole for CRPC. Bone metastases were present in 70% of patients, and visceral involvement was present in 18%. Three patients (9%) had locally advanced disease without distant metastases. Fasted or fed cohorts received abiraterone acetate doses of 250, 500, 750, or 1,000 mg daily. Single-dose pharmacokinetic analyses were performed before continuous daily dosing. Results Adverse events were predominantly grade 1 or 2. No dose-limiting toxicities were observed. Hypertension (grade 3, 12%) and hypokalemia (grade 3, 6%; grade 4, 3%) were the most frequent serious toxicities and responded to medical management. Confirmed >= 50% PSA declines at week 12 were seen in 18 (55%) of 33 patients, including nine (47%) of 19 patients with prior ketoconazole therapy and nine (64%) of 14 patients without prior ketoconazole therapy. Substantial declines in circulating androgens and increases in mineralocorticoids were seen with all doses. Conclusion Abiraterone acetate was well tolerated and demonstrated activity in CRPC, including in patients previously treated with ketoconazole. Continued clinical study is warranted. C1 [Ryan, Charles J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA. Univ Calif San Francisco, Urol Oncol Program, San Francisco, CA 94143 USA. Cougar Biotechnol, Los Angeles, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Drug Metab & Pharmacokinet Team, Inst Canc Res, Sutton, Surrey, England. RP Ryan, CJ (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, 1600 Divisadero St, San Francisco, CA 94115 USA. EM ryanc@medicine.ucsf.edu FU Cougar Biotechnology; Department of Defense Prostate Cancer Clinical Trials Consortium; National Institutes of Health [K23CA115775] FX Supported by Cougar Biotechnology, the Department of Defense Prostate Cancer Clinical Trials Consortium, and Grant No. K23CA115775 (C.J.R.) from the National Institutes of Health. V. M. and F. R. are employees of The Institute of Cancer Research, which has a commercial interest in the development of abiraterone and operates a rewards to inventors scheme. The Institute of Cancer Research has been involved in a commercial collaboration with Cougar Biotechnology. NR 19 TC 235 Z9 240 U1 2 U2 11 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 MAR 20 PY 2010 VL 28 IS 9 BP 1481 EP 1488 DI 10.1200/JCO.2009.24.1281 PG 8 WC Oncology SC Oncology GA 572IR UT WOS:000275824600008 PM 20159824 ER PT J AU Danila, DC Morris, MJ de Bono, JS Ryan, CJ Denmeade, SR Smith, MR Taplin, ME Bubley, GJ Kheoh, T Haqq, C Molina, A Anand, A Koscuiszka, M Larson, SM Schwartz, LH Fleisher, M Scher, HI AF Danila, Daniel C. Morris, Michael J. de Bono, Johann S. Ryan, Charles J. Denmeade, Samuel R. Smith, Matthew R. Taplin, Mary-Ellen Bubley, Glenn J. Kheoh, Thian Haqq, Christopher Molina, Arturo Anand, Aseem Koscuiszka, Michael Larson, Steve M. Schwartz, Lawrence H. Fleisher, Martin Scher, Howard I. TI Phase II Multicenter Study of Abiraterone Acetate Plus Prednisone Therapy in Patients With Docetaxel-Treated Castration-Resistant Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CIRCULATING TUMOR-CELLS; ADRENAL ANDROGENS; DOSE KETOCONAZOLE; END-POINTS; TESTOSTERONE; PROGRESSION; EXPRESSION; SURVIVAL; TRIAL; CYP17 AB Purpose Persistence of ligand-mediated androgen receptor signaling has been documented in castration-resistant prostate cancers (CRPCs). Abiraterone acetate (AA) is a potent and selective inhibitor of CYP17, which is required for androgen biosynthesis in the testes, adrenal glands, and prostate tissue. This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy. Patients and Methods Fifty-eight men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received AA (1,000 mg daily) with prednisone (5 mg twice daily). Twenty-seven (47%) patients had received prior ketoconazole. The primary outcome was >= 50% prostate-specific antigen (PSA) decline, with objective response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and changes in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and circulating tumor cell (CTC) numbers. Safety was also evaluated. Results A >= 50% decline in PSA was confirmed in 22 (36%) patients, including 14 (45%) of 31 ketoconazole-naive and seven (26%) of 27 ketoconazole-pretreated patients. Partial responses were seen in four (18%) of 22 patients with RECIST-evaluable target lesions. Improved ECOG PS was seen in 28% of patients. Median time to PSA progression was 169 days (95% CI, 82 to 200 days). CTC conversions with treatment from >= 5 to < 5 were noted in 10 (34%) of 29 patients. The majority of AA-related adverse events were grade 1 to 2, and no AA-related grade 4 events were seen. Conclusion AA plus prednisone was well tolerated, with encouraging antitumor activity in heavily pretreated CRPC patients. The incidence of mineralocorticoid-related toxicities (hypertension or hypokalemia) was reduced by adding low-dose prednisone. The combination of AA plus prednisone is recommended for phase III investigations. C1 Cornell Univ, Dept Med, Joan & Sanford E Weill Coll Med, Ithaca, NY USA. [Scher, Howard I.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Sidney Kimmel Ctr Prostate & Urol Canc, Dept Med, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Dept Radiol, Clin Labs, New York, NY 10065 USA. Royal Marsden Hosp, Canc Res United Kingdom Ctr Canc Therapeut, Inst Canc Res, London SW3 6JJ, England. Univ Calif San Francisco, San Francisco Comprehens Canc Ctr, San Francisco, CA USA. Cougar Biotechnol, Dept Clin Res & Dev, Los Angeles, CA USA. Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Chem Therapeut Program, Baltimore, MD USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Scher, HI (reprint author), Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Sidney Kimmel Ctr Prostate & Urol Canc, Dept Med, 1275 York Ave, New York, NY 10065 USA. EM Scherh@mskcc.org RI Anand, Aseem/P-1214-2014; OI Anand, Aseem/0000-0002-3606-540X; Morris, Michael J./0000-0002-9454-0096 FU Cougar Biotechnology; Memorial Sloan-Kettering Cancer Center Specialized Program of Research Excellence (SPORE) [P50 CA92629]; Department of Defense Prostate Cancer Research Program [PC051382]; Prostate Cancer Foundation FX Supported by Cougar Biotechnology, the Memorial Sloan-Kettering Cancer Center Specialized Program of Research Excellence (SPORE) Grant in Prostate Cancer (P50 CA92629), the Department of Defense Prostate Cancer Research Program (PC051382) and the Prostate Cancer Foundation. NR 32 TC 264 Z9 273 U1 0 U2 11 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 MAR 20 PY 2010 VL 28 IS 9 BP 1496 EP 1501 DI 10.1200/JCO.2009.25.9259 PG 6 WC Oncology SC Oncology GA 572IR UT WOS:000275824600010 PM 20159814 ER PT J AU Slatore, CG Chien, JW Au, DH Satia, JA White, E AF Slatore, Christopher G. Chien, Jason W. Au, David H. Satia, Jessie A. White, Emily TI Lung Cancer and Hormone Replacement Therapy: Association in the Vitamins and Lifestyle Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; GROWTH-FACTOR RECEPTOR; ESTROGEN-RECEPTOR; REPRODUCTIVE FACTORS; BETA-CAROTENE; WOMEN; RISK; SMOKING; COHORT; EPIDEMIOLOGY AB Purpose Lung cancer is the leading cause of cancer-related mortality among women. The role of hormone replacement therapy (HRT) in lung cancer development is unclear. Patients and Methods We evaluated a prospective cohort of 36,588 peri-and postmenopausal women aged 50 to 76 years from Washington State recruited in 2000 to 2002 (Vitamins and Lifestyle [VITAL] Study). Lung cancer cases (n = 344) were identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry during 6 years of follow-up. Hazard ratios (HRs) associated with use and duration of specific HRT formulations were calculated for total incident lung cancer, specific morphologies, and cancer by stage at diagnosis. Results After adjusting for smoking, age, and other potential confounders, there was an increased risk of incident lung cancer associated with increasing duration of estrogen plus progestin (E + P) use (HR = 1.27 for E + P use 1 to 9 years, 95% CI, 0.91 to 1.78; and HR = 1.48 for E + P use >= 10 years, 95% CI, 1.03 to 2.12; P for trend = . 03). There was no association with duration of unopposed estrogen use. Duration of E + P use was associated with an advanced stage at diagnosis (P for trend = .03). Conclusion Use of E + P increased the risk of incident lung cancer in a duration-dependent manner, with an approximate 50% increased risk for use of 10 years or longer. These findings may be helpful for informing women of their risk of developing lung cancer and delineating important pathways involved in hormone metabolism and lung cancer. C1 [Slatore, Christopher G.] Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. Univ Washington, Div Pulm & Crit Care, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Slatore, CG (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,R&D 66, Portland, OR 97239 USA. EM slatore@ohsu.edu OI Slatore, Christopher/0000-0003-0958-8122 FU CHEST Foundation of the American College of Chest Physicians; LUNGevity Foundation; National Institutes of Health [CA130328, CA74846, CA96556, CA119683]; Department of Veterans Affairs; Portland Veterans Affairs Medical Center, Portland, OR; Veterans Affairs Puget Sound Health Care System, Seattle, WA FX Supported by the CHEST Foundation of the American College of Chest Physicians and the LUNGevity Foundation to C. G. S. This work was also supported by the National Institutes of Health (Grant No. CA130328 to C.G.S., CA74846 to E.W., and CA96556 and CA119683 to J.S.). C.G.S. and D.H.A. were supported by the Department of Veterans Affairs. This study is the result of work supported by resources from the Portland Veterans Affairs Medical Center, Portland, OR, and Veterans Affairs Puget Sound Health Care System, Seattle, WA. NR 49 TC 52 Z9 56 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2010 VL 28 IS 9 BP 1540 EP 1546 DI 10.1200/JCO.2009.25.9739 PG 7 WC Oncology SC Oncology GA 572IR UT WOS:000275824600017 PM 20159813 ER PT J AU Canellos, GP Abramson, JS Fisher, DC LaCasce, AS AF Canellos, George P. Abramson, Jeremy S. Fisher, David C. LaCasce, Ann S. TI Treatment of Favorable, Limited-Stage Hodgkin's Lymphoma With Chemotherapy Without Consolidation by Radiation Therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INVOLVED-FIELD RADIOTHERAPY; COMBINED-MODALITY THERAPY; RANDOMIZED-TRIALS; 2 CYCLES; DISEASE; ABVD; VINBLASTINE; BLEOMYCIN; RISK; METAANALYSIS AB Purpose Limited-stage Hodgkin's lymphoma (HL) has been treated with radiation alone or radiation combined with chemotherapy. Although results in progression-free survival and overall survival have been excellent, the long-term, radiation-induced, toxic cardiac and secondary oncologic complications occurring in succeeding decades have compromised survival of young patients. This study examines the impact of chemotherapy alone in treatment of limited-stage, nonbulky HL, radiation therapy eliminated from primary treatment. Patients and Methods From 1992 to May 2008, 71 patients with a median age of 29 years (range, 17-44 years) with stages I and II HL without bulky nodes were treated with six cycles of classic combination doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Two patients received six cycles of ABVD-like modification. Two patients received four cycles of ABVD. The ABVD regimen was known to be curative in more advanced disease without radiation therapy. Results All patients achieved a clinical complete response (CR) or CR unconfirmed. After a median follow-up of at least 60 months (range, at least 12 to at least 204 months), six patients experienced relapse at 6, 10, 11, 16, 20, and 58 months. All relapses occurred at site of presenting disease. No patients have died. Salvage therapy was successful with second-line chemotherapy/radiation and autologous stem-cell transplantation. Conclusion Six cycles of ABVD is an effective and safe treatment for limited-stage, nonbulky HL and would spare young patients radiation toxicity. Interim positron emission tomography/computed tomography scans in current and future trials may identify those patients who require less than six cycles of chemotherapy. C1 [Canellos, George P.] Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Canellos, GP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM george_canellos@dfci.harvard.edu NR 22 TC 27 Z9 29 U1 0 U2 0 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 MAR 20 PY 2010 VL 28 IS 9 BP 1611 EP 1615 DI 10.1200/JCO.2009.25.3260 PG 5 WC Oncology SC Oncology GA 572IR UT WOS:000275824600027 PM 20159818 ER PT J AU King, JC Lawrence, TS Murphy, SB Davidson, NE Mayer, RJ AF King, Jennifer C. Lawrence, Theodore S. Murphy, Sharon B. Davidson, Nancy E. Mayer, Robert J. TI The American Society of Clinical Oncology Cancer Foundation Grants Program: A 25-Year Report and a Look Toward the Future SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article AB The American Society of Clinical Oncology (ASCO) Grants Program began in 1984 with a single $16,000 grant to a young investigator for start-up research funding. In 2009, the Grants Program, now administered by The ASCO Cancer Foundation, awarded more than $6.5 million to 70 different investigators. This article, celebrating the 25th anniversary of this initiative, describes the history and evolution of the Grants Program, attempts to measure the impact of the program on clinical cancer research through an analysis of the career paths of past recipients, and addresses challenges that the program will face as it enters its second 25 years. C1 [Mayer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. Amer Soc Clin Oncol Canc Fdn, Alexandria, VA USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Natl Acad Sci, Inst Med, Washington, DC 20418 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Robert_Mayer@dfci.harvard.edu RI King, Jennifer/F-8318-2010 NR 6 TC 2 Z9 2 U1 0 U2 0 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 MAR 20 PY 2010 VL 28 IS 9 BP 1616 EP 1621 DI 10.1200/JCO.2009.27.4621 PG 6 WC Oncology SC Oncology GA 572IR UT WOS:000275824600028 PM 20177012 ER PT J AU Lee, JM Zhang, J Su, AI Walker, JR Wiltshire, T Kang, K Dragileva, E Gillis, T Lopez, ET Boily, MJ Cyr, M Kohane, I Gusella, JF MacDonald, ME Wheeler, VC AF Lee, Jong-Min Zhang, Jie Su, Andrew I. Walker, John R. Wiltshire, Tim Kang, Kihwa Dragileva, Ella Gillis, Tammy Lopez, Edith T. Boily, Marie-Josee Cyr, Michel Kohane, Isaac Gusella, James F. MacDonald, Marcy E. Wheeler, Vanessa C. TI HA novel approach to investigate tissue-specific trinucleotide repeat instability SO BMC SYSTEMS BIOLOGY LA English DT Article ID UNSTABLE TRIPLET REPEATS; KNOCK-IN MOUSE; CAG REPEAT; HUNTINGTONS-DISEASE; SOMATIC INSTABILITY; TRANSGENIC MICE; CTG REPEAT; EXPANSION; MUTATION; VULNERABILITY AB Background: In Huntington's disease (HD), an expanded CAG repeat produces characteristic striatal neurodegeneration. Interestingly, the HD CAG repeat, whose length determines age at onset, undergoes tissue-specific somatic instability, predominant in the striatum, suggesting that tissue-specific CAG length changes could modify the disease process. Therefore, understanding the mechanisms underlying the tissue specificity of somatic instability may provide novel routes to therapies. However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors. Results: Here we describe a novel approach to gain insight into the factors responsible for the tissue specificity of somatic instability. Using accurate genetic knock-in mouse models of HD, we developed a reliable, high-throughput method to quantify tissue HD CAG repeat instability and integrated this with genome-wide bioinformatic approaches. Using tissue instability quantified in 16 tissues as a phenotype and tissue microarray gene expression as a predictor, we built a mathematical model and identified a gene expression signature that accurately predicted tissue instability. Using the predictive ability of this signature we found that somatic instability was not a consequence of pathogenesis. In support of this, genetic crosses with models of accelerated neuropathology failed to induce somatic instability. In addition, we searched for genes and pathways that correlated with tissue instability. We found that expression levels of DNA repair genes did not explain the tissue specificity of somatic instability. Instead, our data implicate other pathways, particularly cell cycle, metabolism and neurotransmitter pathways, acting in combination to generate tissue-specific patterns of instability. Conclusion: Our study clearly demonstrates that multiple tissue factors reflect the level of somatic instability in different tissues. In addition, our quantitative, genome-wide approach is readily applicable to high-throughput assays and opens the door to widespread applications with the potential to accelerate the discovery of drugs that alter tissue instability. C1 [Lee, Jong-Min; Dragileva, Ella; Gillis, Tammy; Lopez, Edith T.; Gusella, James F.; MacDonald, Marcy E.; Wheeler, Vanessa C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Zhang, Jie; Su, Andrew I.; Walker, John R.; Wiltshire, Tim] Novartis Res Fdn, Genom Inst, San Diego, CA USA. [Kang, Kihwa] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Boily, Marie-Josee; Cyr, Michel] Univ Quebec, Neurosci Res Grp, Trois Rivieres, PQ GA9 5H7, Canada. [Kohane, Isaac] Childrens Hosp, Informat Program, Boston, MA 02115 USA. RP Lee, JM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM jlee51@partners.org; wheeler@helix.mgh.harvard.edu RI Kohane, Isaac Kohane/K-3716-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Su, Andrew I./0000-0002-9859-4104 FU NINDS [NS049206, NS16367, NS32765]; NCBC [LM008748]; Hereditary Disease Foundation; Canada Research Chair in Molecular Neuropharmacology; Huntington's Disease Society of America; Delta Squared FX We thank James W. MacDonald, Danh V. Nguyen, Jason M. Laramie, and Partners Research Computing (Jerry Xu and Dennis Gurgle) for technical assistance. Supported by NINDS grants NS049206 (to VCW), NS16367 (to JFG and MEM, HD Center Without Walls), and NS32765 (to MEM), NCBC grant LM008748 (to IK), the Hereditary Disease Foundation (to MC), Canada Research Chair in Molecular Neuropharmacology (to MC), and the Huntington's Disease Society of America (Coalition for the Cure, to JFG and MEM). We also thank Delta Squared for supporting this project. NR 31 TC 38 Z9 38 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1752-0509 J9 BMC SYST BIOL JI BMC Syst. Biol. PD MAR 19 PY 2010 VL 4 AR 29 DI 10.1186/1752-0509-4-29 PG 16 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 586AB UT WOS:000276871700001 PM 20302627 ER PT J AU Garrett, WS Gordon, JI Glimcher, LH AF Garrett, Wendy S. Gordon, Jeffrey I. Glimcher, Laurie H. TI Homeostasis and Inflammation in the Intestine SO CELL LA English DT Review ID EPITHELIAL TIGHT JUNCTIONS; GENOME-WIDE ASSOCIATION; MESENTERIC LYMPH-NODES; ILEAL CROHNS-DISEASE; T-BET DEFICIENCY; DENDRITIC CELLS; IMMUNE-SYSTEM; ENTEROENDOCRINE CELLS; ULCERATIVE-COLITIS; GUT MICROBIOTA AB The gut is home to our largest collection of microbes. The ability of the immune system to coevolve with the microbiota during postnatal life allows the host and microbiota to coexist in a mutually beneficial relationship. Failure to achieve or maintain equilibrium between a host and its microbiota has negative consequences for both intestinal and systemic health. In this Review, we consider the many cellular and molecular methods by which inflammatory responses are regulated to maintain intestinal homeostasis and the disease states that can ensue when this balance is lost. C1 [Garrett, Wendy S.; Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Garrett, Wendy S.; Glimcher, Laurie H.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci, St Louis, MO 63108 USA. [Glimcher, Laurie H.] Massachusetts Gen Hosp East, Ragon Inst MGH Harvard MIT, Boston, MA 02129 USA. RP Garrett, WS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM wgarrett@hsph.harvard.edu; lglimche@hsph.harvard.edu FU National Institutes of Health [AI32412, CA112663]; Burroughs Wellcome Fund; Crohn's and Colitis Foundation of America FX The authors thank the members of the Glimcher and Gordon labs for helpful discussions. This work was supported by National Institutes of Health grants AI32412 and CA112663 (L.H.G.), the Burroughs Wellcome Fund, and the Crohn's and Colitis Foundation of America. L. H. G. is a member of the Board of Directors of and holds equity in the Bristol Myers Squibb Corporation. NR 121 TC 271 Z9 280 U1 9 U2 69 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 19 PY 2010 VL 140 IS 6 BP 859 EP 870 DI 10.1016/j.cell.2010.01.023 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 571IX UT WOS:000275746600010 PM 20303876 ER PT J AU Zhang, C Browne, A Child, D DiVito, JR Stevenson, JA Tanzi, RE AF Zhang, Can Browne, Andrew Child, Daniel DiVito, Jason R. Stevenson, Jesse A. Tanzi, Rudolph E. TI Loss of Function of ATXN1 Increases Amyloid beta-Protein Levels by Potentiating beta-Secretase Processing of beta-Amyloid Precursor Protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MICE LACKING ATAXIN-1; ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASE; SPINOCEREBELLAR ATAXIA; APP; CELLS; SCA1; PRESENILIN-1; TRAFFICKING; ASSOCIATION AB Alzheimer disease (AD) is a devastating neurodegenerative disease with complex and strong genetic inheritance. Four genes have been established to either cause familial early onset AD (APP, PSEN1, and PSEN2) or to increase susceptibility for late onset AD (APOE). To date similar to 80% of the late onset AD genetic variance remains elusive. Recently our genome-wide association screen identified four novel late onset AD candidate genes. Ataxin 1 (ATXN1) is one of these four AD candidate genes and has been indicated to be the disease gene for spinocerebellar ataxia type 1, which is also a neurodegenerative disease. Mounting evidence suggests that the excessive accumulation of A beta, the proteolytic product of beta-amyloid precursor protein (APP), is the primary AD pathological event. In this study, we ask whether ATXN1 may lead to AD pathogenesis by affecting A beta and APP processing utilizing RNA interference in a human neuronal cell model and mouse primary cortical neurons. We show that knock-down of ATXN1 significantly increases the levels of both A beta 40 and A beta 42. This effect could be rescued with concurrent overexpression of ATXN1. Moreover, overexpression of ATXN1 decreased A beta levels. Regarding the underlying molecular mechanism, we show that the effect of ATXN1 expression on A beta levels is modulated via beta-secretase cleavage of APP. Taken together, ATXN1 functions as a genetic risk modifier that contributes to AD pathogenesis through a loss-of-function mechanism by regulating beta-secretase cleavage of APP and A beta levels. C1 [Zhang, Can; Browne, Andrew; Child, Daniel; DiVito, Jason R.; Stevenson, Jesse A.; Tanzi, Rudolph E.] Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis,Dept Neurol, Genet & Aging Res Unit,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis,Dept Neurol, Genet & Aging Res Unit,Massachusetts Gen Hosp, 114 16th St, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu FU NIMH; Cure Alzheimers Fund; Massachusetts General Hospital Fund for Medical Discovery (FMD) FX This work was supported, in whole or in part, by the NIMH, the Cure Alzheimers Fund, and the Massachusetts General Hospital Fund for Medical Discovery (FMD). NR 35 TC 25 Z9 25 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 19 PY 2010 VL 285 IS 12 BP 8515 EP 8526 DI 10.1074/jbc.M109.079079 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 568VZ UT WOS:000275553700003 PM 20097758 ER PT J AU Sun, W Jin, JF Xu, RJ Hu, W Szulc, ZM Bielawski, J Obeid, LM Mao, CG AF Sun, Wei Jin, Junfei Xu, Ruijuan Hu, Wei Szulc, Zdzislaw M. Bielawski, Jacek Obeid, Lina M. Mao, Cungui TI Substrate Specificity, Membrane Topology, and Activity Regulation of Human Alkaline Ceramidase 2 (ACER2) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MITOCHONDRIAL CERAMIDASE; SACCHAROMYCES-CEREVISIAE; MOLECULAR-CLONING; ACID CERAMIDASE; GOLGI-APPARATUS; SPHINGOSINE; DISEASE; ENZYME; CELLS AB Human alkaline ceramidase 2 (ACER2) plays an important role in cellular responses by regulating the hydrolysis of ceramides in cells. Here we report its biochemical characterization, membrane topology, and activity regulation. Recombinant ACER2 was expressed in yeast mutant cells (Delta ypc1 Delta ydc1) that lack endogenous ceramidase activity, and microsomes from ACER2-expressiong yeast cells were used to biochemically characterize ACER2. ACER2 catalyzed the hydrolysis of various ceramides and followed Michaelis-Menten kinetics. ACER2 required Ca(2+) for both its in vitro and cellular activities. ACER2 has 7 putative transmembrane domains, and its amino (N) and carboxyl (C) termini were found to be oriented in the lumen of the Golgi complex and cytosol, respectively. ACER2 mutant (ACER2 Delta N36) lacking the N-terminal tail (the first 36 amino acid residues) exhibited undetectable activity and was mislocalized to the endoplasmic reticulum, suggesting that the N-terminal tail is necessary for both ACER2 activity and Golgi localization. ACER2 mutant (ACER2 Delta N13) lacking the first 13 residues was also mislocalized to the endoplasmic reticulum although it retained ceramidase activity. Overexpression of ACER2, ACER2 Delta N13, but not ACER2 Delta N36 increased the release of sphingosine 1-phosphate from cells, suggesting that its mislocalization does not affect the ability of ACER2 to regulate sphingosine 1-phosphate secretion. However, overexpression of ACER2 but not ACER2 Delta N13 or ACER2 Delta N36 inhibited the glycosylation of integrin beta 1 subunit and Lamp1, suggesting that its mistargeting abolishes the ability of ACER2 to regulation protein glycosylation. These data suggest that ACER2 has broad substrate specificity and requires Ca(2+) for its activity and that ACER2 has the cytosolic C terminus and luminal N terminus, which are essential for its activity, correct cellular localization, and regulation for protein glycosylation. C1 [Sun, Wei; Jin, Junfei; Xu, Ruijuan; Hu, Wei; Obeid, Lina M.; Mao, Cungui] Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. [Szulc, Zdzislaw M.; Bielawski, Jacek; Obeid, Lina M.; Mao, Cungui] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Hosp, Charleston, SC 29425 USA. RP Mao, CG (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, 114 Doughty St,Rm 646,STB,POB 250779, Charleston, SC 29425 USA. EM maoc@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [R01CA104834]; Veterans Affairs Merit award FX This work was supported, in whole or in part, by National Institutes of Health Grant R01CA104834 (to C. M.) and a Veterans Affairs Merit award (to L.M.O.). NR 27 TC 22 Z9 24 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 19 PY 2010 VL 285 IS 12 BP 8995 EP 9007 DI 10.1074/jbc.M109.069203 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 568VZ UT WOS:000275553700051 PM 20089856 ER PT J AU Lee, K Ambrose, Z Martin, TD Oztop, I Mulky, A Julias, JG Vandegraaff, N Baumann, JG Wang, R Yuen, W Takemura, T Shelton, K Taniuchi, I Li, Y Sodroski, J Littman, DR Coffin, JM Hughes, SH Unutmaz, D Engelman, A KewalRamani, VN AF Lee, KyeongEun Ambrose, Zandrea Martin, Thomas D. Oztop, Ilker Mulky, Alok Julias, John G. Vandegraaff, Nick Baumann, Joerg G. Wang, Rui Yuen, Wendy Takemura, Taichiro Shelton, Kenneth Taniuchi, Ichiro Li, Yuan Sodroski, Joseph Littman, Dan R. Coffin, John M. Hughes, Stephen H. Unutmaz, Derya Engelman, Alan KewalRamani, Vineet N. TI Flexible Use of Nuclear Import Pathways by HIV-1 SO CELL HOST & MICROBE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL DNA FLAP; FACTOR-I-M; NONDIVIDING CELLS; PREINTEGRATION COMPLEX; MATRIX PROTEIN; PORE COMPLEX; INFECTION; TYPE-1; LOCALIZATION AB HIV-1 replication requires transport of nascent viral DNA and associated virion proteins, the retroviral preintegration complex (PIG), into the nucleus. Too large for passive diffusion through nuclear pore complexes (NPCs), PICs use cellular nuclear transport mechanisms and nucleoporins (NUPs), the NPC components that permit selective nuclear-cytoplasmic exchange, but the details remain unclear. Here we identify a fragment of the cleavage and polyadenylation factor 6, CPSF6, as a potent inhibitor of HIV-1 infection. When enriched in the cytoplasm, CPSF6 prevents HIV-1 nuclear entry by targeting the viral capsid (CA). HIV-1 harboring the N74D mutation in CA fails to interact with CPSF6 and evades the nuclear import restriction. Interestingly, whereas wild-type HIV-1 requires NUP153, N74D HIV-1 mimics feline immunodeficiency virus nuclear import requirements and is more sensitive to NUP155 depletion. These findings reveal a remarkable flexibility in HIV-1 nuclear transport and highlight a single residue in CA as essential in regulating interactions with NUPs. C1 [Lee, KyeongEun; Ambrose, Zandrea; Martin, Thomas D.; Mulky, Alok; Baumann, Joerg G.; Yuen, Wendy; Takemura, Taichiro; Shelton, Kenneth; Hughes, Stephen H.; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Oztop, Ilker; Vandegraaff, Nick; Li, Yuan; Sodroski, Joseph; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Julias, John G.] SAIC Frederick, Frederick, MD 21702 USA. [Wang, Rui; Unutmaz, Derya] NYU, Sch Med, Dept Pathol & Microbiol, New York, NY 10016 USA. [Littman, Dan R.] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. [Littman, Dan R.] NYU, Sch Med, Mol Pathogenesis Program, Skirball Inst Biomol Med, New York, NY 10016 USA. [Taniuchi, Ichiro] Riken Res Ctr Allergy & Immunol, Lab Transcript Regulat, Yokohama, Kanagawa 2300045, Japan. [Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Sackler Sch Biomed Sci, Boston, MA 02111 USA. RP KewalRamani, VN (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM vineet@mail.nih.gov RI Li, Yuan/B-4098-2013; Taniuchi, Ichiro/N-6399-2015 OI Taniuchi, Ichiro/0000-0002-9853-9068 FU National Cancer Institute's intramural Center for Cancer Research; HIV Drug Resistance Program; National Institutes of Health [A152014, A1033303, A1033856, A149131, CA0894, A1063987, A107609441]; American Foundation for AIDS Research postdoctoral fellowship [106404-33-RFMC]; George Kirby Foundation FX We thank Eric Freed for manuscript comments; Paul Bieniasz, Michael Emerman, Eric Freed, and Masahiro Yamashita for discussions; Julie Tang for assistance; and Sabine Dettwiler, Michael Emerman, Eric Freed, John Kappes, Walter Keller, Ned Landau, Eric Poeschla, Wes Sundquist, and Uta von Schwedler for reagents. This work was supported by the National Cancer Institute's intramural Center for Cancer Research, which supports the HIV Drug Resistance Program (S.H.H., V.N.K.); National Institutes of Health (NH) grants to A.E. (A152014), D.R.L. (A1033303; A1033856), D.U. (A149131), J.M.C. (CA089441), and J.S. (A1063987; A1076094); and an American Foundation for AIDS Research postdoctoral fellowship to Z.A. (106404-33-RFMC). J.M.C. was a Research Professor of the American Cancer Society, with support from the George Kirby Foundation. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 51 TC 167 Z9 169 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD MAR 18 PY 2010 VL 7 IS 3 BP 221 EP 233 DI 10.1016/j.chom.2010.02.007 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 573XA UT WOS:000275947500007 PM 20227665 ER PT J AU Cichowski, K Janne, PA AF Cichowski, Karen Jaenne, Pasi A. TI DRUG DISCOVERY Inhibitors that activate SO NATURE LA English DT Editorial Material ID SQUAMOUS-CELL CARCINOMAS; BRAF C1 [Cichowski, Karen] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Cichowski, K (reprint author), Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM kcichowski@rics.bwh.harvard.edu; pjanne@partners.org NR 9 TC 48 Z9 48 U1 0 U2 5 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 MAR 18 PY 2010 VL 464 IS 7287 BP 358 EP 359 DI 10.1038/464358a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 570FG UT WOS:000275657100029 PM 20237552 ER PT J AU Boudsocq, M Willmann, MR McCormack, M Lee, H Shan, LB He, P Bush, J Cheng, SH Sheen, J AF Boudsocq, Marie Willmann, Matthew R. McCormack, Matthew Lee, Horim Shan, Libo He, Ping Bush, Jenifer Cheng, Shu-Hua Sheen, Jen TI Differential innate immune signalling via Ca2+ sensor protein kinases SO NATURE LA English DT Article ID GENE-EXPRESSION ANALYSIS; PLANT DEFENSE; MOLECULAR-PATTERNS; ARABIDOPSIS; CALCIUM; PERCEPTION; RESISTANCE; FLAGELLIN; IDENTIFICATION; TRANSDUCTION AB Innate immunity represents the first line of inducible defence against microbial infection in plants and animals(1-3). In both kingdoms, recognition of pathogen- or microbe-associated molecular patterns (PAMPs or MAMPs, respectively), such as flagellin, initiates convergent signalling pathways involving mitogen-activated protein kinase ( MAPK) cascades and global transcriptional changes to boost immunity(1-4). Although Ca2+ has long been recognized as an essential and conserved primary mediator in plant defence responses, how Ca2+ signals are sensed and relayed into early MAMP signalling is unknown(5,6). Using a functional genomic screen and genome-wide gene expression profiling, here we show that four calcium-dependent protein kinases (CDPKs) are Ca2+-sensor protein kinases critical for transcriptional reprogramming in plant innate immune signalling. Unexpectedly, CDPKs and MAPK cascades act differentially in four MAMP-mediated regulatory programs to control early genes involved in the synthesis of defence peptides and metabolites, cell wall modifications and redox signalling. Transcriptome profile comparison suggests that CDPKs are the convergence point of signalling triggered by most MAMPs. Double, triple and quadruple cpk mutant plants display progressively diminished oxidative burst and gene activation induced by the 22-amino-acid peptide flg22, as well as compromised pathogen defence. In contrast to negative roles of calmodulin and a calmodulin-activated transcription factor in plant defence(7,8), the present study reveals Ca2+ signalling complexity and demonstrates key positive roles of specific CDPKs in initial MAMP signalling. C1 [Boudsocq, Marie; Willmann, Matthew R.; McCormack, Matthew; Lee, Horim; Shan, Libo; He, Ping; Bush, Jenifer; Cheng, Shu-Hua; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Boudsocq, Marie; Willmann, Matthew R.; McCormack, Matthew; Lee, Horim; Shan, Libo; He, Ping; Bush, Jenifer; Cheng, Shu-Hua; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Boudsocq, Marie; Willmann, Matthew R.; McCormack, Matthew; Lee, Horim; Shan, Libo; He, Ping; Bush, Jenifer; Cheng, Shu-Hua; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Boudsocq, M (reprint author), CNRS, UPR2355, Inst Sci Vegetal, 1 Ave Terrasse, F-91198 Gif Sur Yvette, France. EM boudsocq@molbio.mgh.harvard.edu; willmann@sas.upenn.edu OI Willmann, Matthew R./0000-0002-4146-8158 FU European Community; NSF; National Science Foundation; National Institute of Health; MGH CCIB FX We thank K. H. Liu and E. Baena-Gonzalez for contributing to the CPK clone collection, O.R. Patharkar for initial microarray data analysis, B. Mueller and G. Tena for offering qPCR primers, M. N. Soler and S. Bolte for assistance on confocal microscopy, C. Lauriere for discussions, S. P. Dinesh-Kumar for VIGS vectors, K. Schreiber and D. Desveaux for the seedling pathogen assay, and A. Gust and T. Nurnberger for the original PGN microarray data. Wethank the Salk Institute, Syngenta Biotechnology and A. Sessions for sharing the Arabidopsis T-DNA collections, and the Arabidopsis Biological Resource Center for providing Arabidopsis mutant seeds. This research has been supported by a Marie Curie International fellowship within the 6th European Community Framework Program to M. B., an NSF predoctoral fellowship to M. R. W., and grants from the National Science Foundation and the National Institute of Health, and the MGH CCIB fund to J. S. NR 38 TC 274 Z9 288 U1 12 U2 123 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 18 PY 2010 VL 464 IS 7287 BP 418 EP U116 DI 10.1038/nature08794 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 570FG UT WOS:000275657100048 PM 20164835 ER PT J AU Young, RH Goodman, A Penson, RT Russell, AH Uppot, RN Tambouret, RH AF Young, Robert H. Goodman, Annekathryn Penson, Richard T. Russell, Anthony H. Uppot, Raul N. Tambouret, Rosemary H. TI Case 8-2010: A 22-Year-Old Woman with Hypercalcemia and a Pelvic Mass - Ovarian small-cell carcinoma, hypercalcemic type SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SERTOLI-LEYDIG CELL; CLINICOPATHOLOGICAL ANALYSIS; TUMORS; SURGERY; CANCER; CHEMOTHERAPY; PREGNANCY; ETOPOSIDE; WOMEN C1 [Young, Robert H.; Tambouret, Rosemary H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Goodman, Annekathryn] Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. [Penson, Richard T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Russell, Anthony H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Uppot, Raul N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Young, Robert H.; Tambouret, Rosemary H.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Goodman, Annekathryn] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Cambridge, MA 02138 USA. [Penson, Richard T.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Russell, Anthony H.] Harvard Univ, Sch Med, Dept Radiat Oncol, Cambridge, MA 02138 USA. [Uppot, Raul N.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 21 TC 7 Z9 7 U1 1 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 MAR 18 PY 2010 VL 362 IS 11 BP 1031 EP 1040 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 570CY UT WOS:000275650400016 PM 20237350 ER PT J AU Curran, M AF Curran, Marjorie TI Haiti - A View from the Ship SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 MassGen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 18 PY 2010 VL 362 IS 11 DI 10.1056/NEJMpv1002319 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 570CY UT WOS:000275650400041 PM 20200363 ER PT J AU Goodman, A AF Goodman, Annekathryn TI Ministry of Touch -- Reflections on Disaster Work after the Haitian Earthquake. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 18 PY 2010 VL 362 IS 11 DI 10.1056/NEJMp1002311 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 570CY UT WOS:000275650400005 PM 20200361 ER PT J AU Liang, MC Ma, J Chen, L Kozlowski, P Qin, W Li, D Goto, J Shimamura, T Hayes, DN Meyerson, M Kwiatkowski, DJ Wong, KK AF Liang, M-C Ma, J. Chen, L. Kozlowski, P. Qin, W. Li, D. Goto, J. Shimamura, T. Hayes, D. N. Meyerson, M. Kwiatkowski, D. J. Wong, K-K TI TSC1 loss synergizes with KRAS activation in lung cancer development in the mouse and confers rapamycin sensitivity SO ONCOGENE LA English DT Article DE lung cancer; TSC1; KRAS; TSC2; mTOR ID TUBEROUS SCLEROSIS COMPLEX; PEUTZ-JEGHERS-SYNDROME; ONCOGENIC K-RAS; TSC1-TSC2 COMPLEX; MAMMALIAN TARGET; MTOR INHIBITORS; BLADDER-CANCER; GENE TSC1; MODEL; LKB1 AB Germline TSC1 or TSC2 mutations cause tuberous sclerosis complex (TSC), a hamartoma syndrome with lung involvement. To explore the potential interaction between TSC1 and KRAS activation in lung cancer, mice in which Tsc1 loss and KrasG12D expression occur in a small fraction of lung epithelial cells were generated. Mice with a combined Tsc1-KrasG12D mutation had dramatically reduced tumor latency (median survival: 11.6-15.6 weeks) in comparison with KrasG12D alone mutant mice (median survival: 27.5 weeks). Tsc1-KrasG12D tumors showed consistent activation of mTOR (mammalian target of rapamycin) C1 and responded to treatment with rapamycin, leading to significantly improved survival, whereas rapamycin had minor effects on cancers in KrasG12D alone mice. Loss of heterozygosity for TSC1 or TSC2 was found in 22% of 86 human lung cancer specimens. However, none of the 80 lung cancer lines studied showed evidence of the lack of expression of either TSC1 or TSC2 or a signaling pattern corresponding to complete loss. These data indicate that Tsc1 loss synergizes with the Kras mutation to enhance lung tumorigenesis in the mouse, but that this is a rare event in human lung cancer. Rapamycin may have unique benefit for patients with lung cancer, for whom the TSC1/TSC2 function is limited. Oncogene (2010) 29, 1588-1597; doi:10.1038/onc.2009.452; published online 7 December 2009 C1 [Ma, J.; Kozlowski, P.; Qin, W.; Goto, J.; Kwiatkowski, D. J.] Brigham & Womens Hosp, Dept Med, Div Translat Med, Boston, MA 02115 USA. [Liang, M-C; Chen, L.; Li, D.; Wong, K-K] Harvard Canc Ctr, Ludwig Ctr Dana Farber, Boston, MA USA. [Liang, M-C; Chen, L.; Li, D.; Shimamura, T.; Meyerson, M.; Wong, K-K] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hayes, D. N.] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC USA. [Meyerson, M.] MIT, Cambridge, MA 02139 USA. [Meyerson, M.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. RP Kwiatkowski, DJ (reprint author), Brigham & Womens Hosp, Dept Med, Div Translat Med, 1 Blackfan Circle,Room 6-216, Boston, MA 02115 USA. EM dk@rics.bwh.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI Hayes, D. Neil/0000-0001-6203-7771 FU NIH [R01 AG2400401, R01 CA122794, K08 AG024004, P01 CA120964]; Sidney Kimmel Foundation for Cancer Research; Joan Scarangello Foundation to Conquer Lung Cancer; Flight Attendant Medical Research Institute FX We thank Kate McNamara and Sara Zaghlul (Dana-Farber Cancer Institute, Boston), Christine Lam, Iza Malinowska-Kolodziej and Mei Zheng (Brigham and Women's Hospital, Boston) for their technical assistance and Roderick T. Bronson (Harvard Medical School, Boston) and Robert Padera and Lucian Chirieac (Brigham and Women's Hospital, Boston) for assistance with pathology review. This study was supported in part by the NIH Grant nos R01 AG2400401 (K-KW), R01 CA122794 (K-KW), K08 AG024004 (K-KW), P01 CA120964 (DJK), the Sidney Kimmel Foundation for Cancer Research (K-KW), the Joan Scarangello Foundation to Conquer Lung Cancer (K-KW and DJK) and the Flight Attendant Medical Research Institute (K-KW). NR 41 TC 26 Z9 27 U1 3 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 18 PY 2010 VL 29 IS 11 BP 1588 EP 1597 DI 10.1038/onc.2009.452 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 570RC UT WOS:000275694700004 PM 19966866 ER PT J AU Worthley, DL Whitehall, VLJ Buttenshaw, RL Irahara, N Greco, SA Ramsnes, I Mallitt, KA Le Leu, RK Winter, J Hu, Y Ogino, S Young, GP Leggett, BA AF Worthley, D. L. Whitehall, V. L. J. Buttenshaw, R. L. Irahara, N. Greco, S. A. Ramsnes, I. Mallitt, K-A Le Leu, R. K. Winter, J. Hu, Y. Ogino, S. Young, G. P. Leggett, B. A. TI DNA methylation within the normal colorectal mucosa is associated with pathway-specific predisposition to cancer SO ONCOGENE LA English DT Article DE DNA methylation; epigenetics; colorectal cancer; carcinogenesis ID NORMAL COLONIC-MUCOSA; MICROSATELLITE INSTABILITY; ULCERATIVE-COLITIS; BRAF MUTATION; CHROMOSOMAL INSTABILITY; PROMOTER METHYLATION; SERRATED ADENOMAS; MOLECULAR-ORIGINS; PHENOTYPE; POLYPS AB There are two major molecular pathways to sporadic colorectal cancer, the chromosomal instability (CIN) and the CpG island methylator phenotype (CIMP) pathways. This study recruited 166 patients undergoing colonoscopy. Biopsy samples were collected from the cecum, transverse colon, sigmoid colon and rectum. DNA methylation was quantified at 'type A' (ESR1, GATA5, HIC1, HPP1, SFRP1) and 'type C' markers (MGMT, MLH1, CDKN2A, MINT2, MINT31, IGF2, CACNA1G, NEU-ROG1, SOCS1, RUNX3), and LINE-1. 'Type A' genes are frequently methylated in normal and neoplastic tissues, proportional to tissue age. 'Type C' methylation is more specific for neoplasia. The last five 'type C' markers comprise a CIMP panel. The mean 'type A' and CIMP-panel methylation Z-scores were calculated. In all, 88 patients had adenomatous lesions, 32 had proximal serrated polyps (PSPs) and 50 were normal. Most 'type A' genes showed direct correlations between methylation and age (ESR1, rho = 0.66, P < 0.0001), with higher methylation distally (ESR1, P < 0.0001). On multivariate analysis, 'type A' methylation was inversely associated with colorectal adenomas (odds ratio 0.23, P < 0.001), the precursor to CIN cancers. CIMP-panel methylation was significantly associated with advanced PSPs (odds ratio = 5.1, P = 0.009), the precursor to CIMP cancers. DNA methylation in normal mucosa varied with age and region and was associated with pathway-specific pathology. In the future, the colorectal field could yield important information and potentially inform clinical practice. Oncogene (2010) 29, 1653-1662; doi:10.1038/onc.2009.449; published online 7 December 2009 C1 [Worthley, D. L.; Whitehall, V. L. J.; Buttenshaw, R. L.; Greco, S. A.; Ramsnes, I.; Leggett, B. A.] Queensland Inst Med Res, Bancroft Ctr, Conjoint Gastroenterol Lab, Herston, Qld 4029, Australia. [Worthley, D. L.; Whitehall, V. L. J.; Buttenshaw, R. L.; Greco, S. A.; Ramsnes, I.; Leggett, B. A.] Royal Brisbane & Womens Hosp, Res Fdn Clin Res Ctr, Brisbane, Qld, Australia. [Irahara, N.; Ogino, S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mallitt, K-A] Queensland Inst Med Res, Stat Unit, Herston, Qld 4029, Australia. [Le Leu, R. K.; Winter, J.; Hu, Y.; Young, G. P.] Flinders Univ S Australia, Flinders Ctr Canc Prevent & Control, Adelaide, SA, Australia. [Ogino, S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, S.] Harvard Univ, Sch Med, Boston, MA USA. RP Worthley, DL (reprint author), Queensland Inst Med Res, Bancroft Ctr, Conjoint Gastroenterol Lab, Rm H07,PO RBH, Herston, Qld 4029, Australia. EM daniel.worthley@uqconnect.edu.au RI Mallitt, Kylie-Ann/E-2240-2011; Leggett, Barbara/D-3579-2011; Whitehall, Vicki/B-6262-2013; Le Leu, Richard/H-4555-2013 OI Mallitt, Kylie-Ann/0000-0002-5722-7287; Whitehall, Vicki/0000-0002-8285-2391; Le Leu, Richard/0000-0003-4704-4943 FU National Health and Medical Research Council [442965]; Gastroenterological Society of Australia; Royal Australasian College of Physicians Cottrell Fellowship; Royal Brisbane and Women's Hospital Foundation; Queensland Smart State PhD award FX We thank the gastroenterologists and gastroenterology nurses who helped to collect samples. This study was funded by a National Health and Medical Research Council project grant (442965), a Gastroenterological Society of Australia post-graduate medical scholarship (DLW), the Royal Australasian College of Physicians Cottrell Fellowship (DLW), a Royal Brisbane and Women's Hospital Foundation Research Grant (VLW, DLW, BAL) and a Queensland Smart State PhD award (DLW). NR 57 TC 53 Z9 57 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 18 PY 2010 VL 29 IS 11 BP 1653 EP 1662 DI 10.1038/onc.2009.449 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 570RC UT WOS:000275694700010 PM 19966864 ER PT J AU Kapoor, JR Kapoor, R AF Kapoor, John R. Kapoor, Roger TI Endovascular Aortic Aneurysm Repair SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID RANDOMIZED CONTROLLED-TRIAL; VASCULAR-SURGERY; MORTALITY C1 [Kapoor, John R.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Kapoor, Roger] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kapoor, JR (reprint author), Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. EM rkapoor4@partners.org NR 5 TC 0 Z9 1 U1 0 U2 1 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 MAR 17 PY 2010 VL 303 IS 11 BP 1035 EP 1035 DI 10.1001/jama.2010.154 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 569KC UT WOS:000275594100013 PM 20233820 ER PT J AU Kahn, KL Adams, JL Weeks, JC Chrischilles, EA Schrag, D Ayanian, JZ Kiefe, CI Ganz, PA Bhoopalam, N Potosky, AL Harrington, DP Fletcher, RH AF Kahn, Katherine L. Adams, John L. Weeks, Jane C. Chrischilles, Elizabeth A. Schrag, Deborah Ayanian, John Z. Kiefe, Catarina I. Ganz, Patricia A. Bhoopalam, Nirmala Potosky, Arnold L. Harrington, David P. Fletcher, Robert H. TI Adjuvant Chemotherapy Use and Adverse Events Among Older Patients With Stage III Colon Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MARGINAL STRUCTURAL MODELS; CARE OUTCOMES RESEARCH; COLORECTAL-CANCER; ELDERLY-PATIENTS; CLINICAL-TRIALS; RANDOMIZED-TRIAL; POOLED ANALYSIS; OF-LIFE; FLUOROURACIL; LEUCOVORIN AB Context Randomized trials suggest adjuvant chemotherapy is effective for older patients with stage III colon cancer. However, older patients are less likely to receive this therapy than younger patients, perhaps because of concern about adverse effects. Objective To evaluate adjuvant chemotherapy use and outcomes for older patients with stage III colon cancer from well-defined population-based settings and health care systems. Design Observational study of adjuvant chemotherapy use and outcomes by age using Poisson regression to estimate the number of adverse events adjusted for demographic and clinical factors, including comorbid illness and specific elements of chemotherapy regimens documented with clinically detailed medical record reviews and patient and surrogate surveys. Setting Five geographically defined regions (Alabama, Iowa, Los Angeles County, northern California, and North Carolina), 5 integrated health care delivery systems, and 15 Veterans Affairs hospitals. Patients Six hundred seventy-five patients diagnosed with stage III colon cancer from 2003 through 2005 who underwent surgical resection and were followed up for as long as 15 months postdiagnosis. Main Outcome Measures Chemotherapy regimen, dose, duration, and annualized mean number of adverse events stratified by age. Results Of 202 patients aged 75 years and older, 101 (50%) received adjuvant chemotherapy compared with 87% of 473 younger patients (difference, 37%; 95% confidence interval [CI], 30%-45%). Among patients who received adjuvant chemotherapy, 14 patients (14%) aged 75 years and older and 178 younger patients (44%) received a regimen containing oxaliplatin (difference, 30%; 95% CI, 21%-38%). Older patients were less likely to continue treatment, such that by 150 days, 99 patients (40%) aged 65 years and older and 68 younger patients (25%) had discontinued chemotherapy (difference, 15%; 95% CI, 7%-23%). Overall, 162 patients (24%) had at least 1 adverse clinical event, with more events among patients treated with vs without adjuvant chemotherapy (mean, 0.39 vs 0.16; difference, 0.23; 95% CI, 0.11-0.36; P<.001). Among patients receiving adjuvant chemotherapy, adjusted rates of late clinical adverse events were lower for patients 75 years and older (mean, 0.28) vs for younger patients (0.35 for ages 18-54 years, 0.52 for ages 55-64 years, and 0.45 for ages 65-74 years; P=.008 for any age effect). Conclusion Among patients with stage III colon cancer who underwent surgical resection and received adjuvant chemotherapy, older patients in the community received less-toxic and shorter chemotherapy regimens, and those treated had fewer adverse events than younger patients. JAMA. 2010; 303(11): 1037-1045 C1 [Kahn, Katherine L.; Adams, John L.] RAND Corp, Santa Monica, CA 90401 USA. [Kahn, Katherine L.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Div Hematol & Med Oncol, Los Angeles, CA USA. [Kahn, Katherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Weeks, Jane C.] Div Populat Sci, Boston, MA USA. [Harrington, David P.] Dept Biostat & Computat Biol, Boston, MA USA. [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chrischilles, Elizabeth A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Ayanian, John Z.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Ayanian, John Z.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Fletcher, Robert H.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02115 USA. [Kiefe, Catarina I.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Bhoopalam, Nirmala] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Potosky, Arnold L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Canc Control Program, Washington, DC 20007 USA. [Fletcher, Robert H.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Fletcher, Robert H.] Univ N Carolina, Dept Social Med, Chapel Hill, NC USA. RP Kahn, KL (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. EM kahn@rand.org FU National Cancer Institute (NCI) [U01 CA093344, U01 CA093348]; Harvard Medical School and Northern California Cancer Center [U01 CA093324]; Dana-Farber Cancer Institute and Cancer Research Network [U01 CA093332]; University of Alabama at Birmingham [U01 CA093329]; University of Iowa [U01 CA01013]; University of North Carolina [U01 CA093326]; Department of Veterans Affairs [U01 CDA093344 [MOU], HARQ 03-438MO-03] FX Funding/Support: The Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium was supported by grants from the National Cancer Institute (NCI) to the statistical coordinating center at the Dana-Farber Cancer Institute (U01 CA093344) and the primary data collection and research centers at RAND Corporation and University of California, Los Angeles (U01 CA093348); Harvard Medical School and Northern California Cancer Center (U01 CA093324); Dana-Farber Cancer Institute and Cancer Research Network (U01 CA093332); University of Alabama at Birmingham (U01 CA093329); University of Iowa (U01 CA01013); and University of North Carolina (U01 CA093326) and by a Department of Veterans Affairs grant to the Durham VA Medical Center (U01 CDA093344 [MOU] and HARQ 03-438MO-03). NR 38 TC 71 Z9 74 U1 1 U2 4 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 MAR 17 PY 2010 VL 303 IS 11 BP 1037 EP 1045 DI 10.1001/jama.2010.272 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 569KC UT WOS:000275594100016 PM 20233821 ER PT J AU Talcott, JA Rossi, C Shipley, WU Clark, JA Slater, JD Niemierko, A Zietman, AL AF Talcott, James A. Rossi, Carl Shipley, William U. Clark, Jack A. Slater, Jerry D. Niemierko, Andrzej Zietman, Anthony L. TI Patient-Reported Long-term Outcomes After Conventional and High-Dose Combined Proton and Photon Radiation for Early Prostate Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; OF-LIFE OUTCOMES; CONFORMAL RADIOTHERAPY; PATIENTS PERCEPTIONS; THERAPY; ADENOCARCINOMA; IRRADIATION; CARCINOMA; SEQUELAE; ESCALATION AB Context Increased radiation doses improve prostate cancer control but also increase toxicity to adjacent normal tissue. Proton radiation may attenuate adverse effects. Objective To determine long-term, patient-reported, dose-related toxicity. Design, Setting, and Patients We performed a post hoc cross-sectional survey of surviving participants in the Proton Radiation Oncology Group (PROG) 9509-a randomized trial comparing 70.2 Gy vs 79.2 Gy of combined photon and proton radiation for 393 men with clinically localized prostate cancer (stage T1b-T2b, prostate-specific antigen <15 ng/mL, and no radiographic evidence of metastasis). The estimated 10-year biochemical progression rate for patients receiving standard dose was 32% (95% confidence interval, 26%-39%) compared with 17% (95% confidence interval, 11%-23%) for patients receiving high dose (P<.001). We surveyed 280 of the surviving 337 patients (83%) from April 2007 to September 2008. Main Outcome Measures Prostate Cancer Symptom Indices, a validated measure of urinary incontinence, urinary obstruction and irritation, bowel problems, and sexual dysfunction, and related quality-of-life instruments. Results At a median of 9.4 years after treatment (range, 7.4-12.1 years), participants' demographic and clinical characteristics were similar. Patient-reported outcomes were reported as mean (SD) scale score for standard dose vs high dose: urinary obstruction/irritation (23.3 [13.7] vs 24.6 [14.0]; P=.36), urinary incontinence (10.6 [17.7] vs 9.7 [15.8]; P=.99), bowel problems (7.7 [7.8] vs 7.9 [9.1]; P=.70), sexual dysfunction (68.2 [34.6] vs 65.9 [34.7]; P=.65), and most other outcomes were also similar, although patients receiving standard dose whose cancers had more often progressed expressed less confidence that their cancers were under control (mean [SD] scale score for standard dose, 76.0 [25.4] vs high dose, 86.2 [17.9]; P<.001). Many patients characterized their urinary and bowel function as normal despite reporting symptoms that, for other prostate cancer patients before and early after cancer treatment, caused substantial distress. Conclusion Among men with clinically localized prostate cancer, treatment with higher-dose radiation compared with standard dose was not associated with an increase in patient-reported prostate cancer symptoms after a median of 9.4 years. JAMA. 2010; 303(11): 1046-1053 C1 [Talcott, James A.] Massachusetts Gen Hosp, MGH Canc Ctr, Ctr Outcomes Res, Boston, MA 02114 USA. [Rossi, Carl; Slater, Jerry D.] Loma Linda Univ, Med Ctr, Loma Linda, CA USA. [Shipley, William U.; Niemierko, Andrzej; Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Clark, Jack A.] Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Clark, Jack A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Talcott, James A.; Shipley, William U.; Niemierko, Andrzej; Zietman, Anthony L.] Harvard Univ, Sch Med, Boston, MA USA. RP Talcott, JA (reprint author), Ctr Outcomes Res, Charlestown Navy Yard,Bldg 120,6th St,2nd Floor, Charlestown, MA 02129 USA. EM jtalcott@partners.org OI Clark, Jack/0000-0002-7424-1670 FU Massachusetts General Hospital, Boston, MA FX Funding/Support: This research was supported by the Bertucci Genitourinary Cancer Research Fund, Massachusetts General Hospital, Boston, MA. NR 31 TC 58 Z9 59 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 MAR 17 PY 2010 VL 303 IS 11 BP 1046 EP 1053 DI 10.1001/jama.2010.287 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 569KC UT WOS:000275594100017 PM 20233822 ER PT J AU Kim, SH Fraser, PE Westaway, D George-Hyslop, PHS Ehrlich, ME Gandy, S AF Kim, Soong Ho Fraser, Paul E. Westaway, David George-Hyslop, Peter H. St. Ehrlich, Michelle E. Gandy, Sam TI Group II Metabotropic Glutamate Receptor Stimulation Triggers Production and Release of Alzheimer's Amyloid beta(42) from Isolated Intact Nerve Terminals SO JOURNAL OF NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; PRECURSOR PROTEIN; TRANSGENIC MICE; IN-VIVO; SYNAPTIC PLASTICITY; CEREBRAL-CORTEX; DISEASE; ACTIVATION; PEPTIDE; KINASE AB Aberrant accumulation of amyloid beta (A beta) oligomers may underlie the cognitive failure of Alzheimer's disease (AD). All species of A beta peptides are produced physiologically during normal brain activity. Therefore, elucidation of mechanisms that interconnect excitatory glutamatergic neurotransmission, synaptic amyloid precursor protein (APP) processing and production of its metabolite, A beta, may reveal synapse-specific strategies for suppressing the pathological accumulation of A beta oligomers and fibrils that characterize AD. To study synaptic APP processing, we used isolated intact nerve terminals (cortical synaptoneurosomes) from TgCRND8 mice, which express a human APP with familial AD mutations. Potassium chloride depolarization caused sustained release from synaptoneurosomes of A beta(42) as well as A beta(40), and appeared to coactivate alpha-, beta-and gamma-secretases, which are known to generate a family of released peptides, including A beta(40) and A beta(42). Stimulation of postsynaptic group I metabotropic glutamate receptor (mGluRs) with DHPG (3,5-dihydroxyphenylglycine) induced a rapid accumulation of APP C-terminal fragments (CTFs) in the synaptoneurosomes, a family of membrane-bound intermediates generated from APP metabolized by alpha- and beta-secretases. Following stimulation with the group II mGluR agonist DCG-IV, levels of APP CTFs in the synaptoneurosomes initially increased but then returned to baseline by 10 min after stimulation. This APP CTF degradation phase was accompanied by sustained accumulation of A beta(42) in the releasate, which was blocked by the group IImGluR antagonist LY341495. These data suggest that group IImGluR may trigger synaptic activation of all three secretases and that suppression of group II mGluR signaling may be a therapeutic strategy for selectively reducing synaptic generation of A beta(42). C1 [Kim, Soong Ho; Ehrlich, Michelle E.; Gandy, Sam] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Gandy, Sam] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. [Fraser, Paul E.; George-Hyslop, Peter H. St.] Univ Toronto, Ctr Res Neurodegenerat Dis, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. [Fraser, Paul E.; George-Hyslop, Peter H. St.] Univ Toronto, Ctr Res Neurodegenerat Dis, Dept Med Neurol, Toronto, ON M5S 1A1, Canada. [Westaway, David] Univ Alberta, Ctr Prions & Prot Folding Dis, Edmonton, AB T6G 2M8, Canada. [George-Hyslop, Peter H. St.] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0XY, England. [Gandy, Sam] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Gandy, S (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM samuel.gandy@mssm.edu FU National Institutes of Health [AG10491]; Cure Alzheimer's Fund; Canadian Institutes of Health Research; Alzheimer Society of Ontario; Alberta Prion Research Institute; Canada Foundation for Innovation; Howard Hughes Medical Institute; Wellcome Trust FX This work was supported by National Institutes of Health Grant AG10491, Cure Alzheimer's Fund, Canadian Institutes of Health Research, the Alzheimer Society of Ontario, the Alberta Prion Research Institute, the Canada Foundation for Innovation, Howard Hughes Medical Institute, and The Wellcome Trust. We thank Loren Khan-Vaughan and Justine Bonet for assistance with mouse colony management. NR 51 TC 45 Z9 46 U1 0 U2 3 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 MAR 17 PY 2010 VL 30 IS 11 BP 3870 EP 3875 DI 10.1523/JNEUROSCI.4717-09.2010 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 571BT UT WOS:000275724800003 PM 20237257 ER PT J AU Ogino, S Stampfer, M AF Ogino, Shuji Stampfer, Meir TI Lifestyle Factors and Microsatellite Instability in Colorectal Cancer: The Evolving Field of Molecular Pathological Epidemiology SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ISLAND METHYLATOR PHENOTYPE; FATTY-ACID SYNTHASE; BODY-MASS INDEX; POPULATION-BASED SAMPLE; KI-RAS MUTATIONS; COLON-CANCER; DIETARY-FOLATE; RECTAL-CANCER; PHYSICAL-ACTIVITY; PATIENT SURVIVAL C1 [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol,Sch Med,Dept Pathol, Boston, MA 02115 USA. [Stampfer, Meir] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji; Stampfer, Meir] Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA. [Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol,Sch Med,Dept Pathol, 44 Binney St,Rm JF-215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [K07 CA122826, P01 CA55075, P01 CA87969] NR 50 TC 87 Z9 89 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 17 PY 2010 VL 102 IS 6 BP 365 EP 367 DI 10.1093/jnci/djq031 PG 3 WC Oncology SC Oncology GA 573CB UT WOS:000275884900001 PM 20208016 ER PT J AU Goldfine, AB Fonseca, V Jablonski, KA Pyle, L Staten, MA Shoelson, SE AF Goldfine, Allison B. Fonseca, Vivian Jablonski, Kathleen A. Pyle, Laura Staten, Myrlene A. Shoelson, Steven E. CA TINSAL-T2D Targeting Inflammation TI The Effects of Salsalate on Glycemic Control in Patients With Type 2 Diabetes A Randomized Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID NF-KAPPA-B; GLOMERULAR-FILTRATION-RATE; INDUCED INSULIN-RESISTANCE; SODIUM-SALICYLATE; IKK-BETA; NONACETYLATED SALICYLATE; CYSTATIN-C; URIC-ACID; ASPIRIN; INFLAMMATION AB Background: Salsalate, a nonacetylated prodrug of salicylate, has been shown to decrease blood glucose concentration in small studies. Objective: To compare the efficacy and safety of salsalate at different doses in patients with type 2 diabetes. Design: Parallel randomized trial with computer-generated randomization and centralized allocation. Patients and investigators, including those assessing outcomes and performing analyses, were masked to group assignment. (ClinicalTrials.gov registration number: NCT00392678) Setting: 3 private practices and 14 universities in the United States. Patients: Persons aged 18 to 75 years with fasting plasma glucose concentrations of 12.5 mmol/L or less (<= 225 mg/dL) and hemoglobin A(1c) (HbA(1c)) levels of 7.0% to 9.5% treated by diet, exercise, and oral medication at stable doses for at least 8 weeks. Intervention: After a 4-week, single-masked run-in period, patients were randomly assigned to receive placebo or salsalate in dosages of 3.0, 3.5, or 4.0 g/d for 14 weeks (27 patients each) in addition to their current therapy. Measurements: Change in HbA(1c) was the primary outcome. Adverse effects and changes in measures of coronary risk and renal function were secondary outcomes. Results: Higher proportions of patients in the 3 salsalate treatment groups experienced decreases in HbA(1c) levels of 0.5% or more from baseline (P = 0.009). Mean HbA(1c) changes were -0.36% (P = 0.02) at 3.0 g/d, -0.34% (P = 0.02) at 3.5 g/d, and -0.49% (P = 0.001) at 4.0 g/d compared with placebo. Other markers of glycemic control also improved in the 3 salsalate groups, as did circulating triglyceride and adiponectin concentrations. Mild hypoglycemia was more common with salsalate; documented events occurred only in patients taking sulfonylureas. Urine albumin concentrations increased in all salsalate groups compared with placebo. The drug was otherwise well tolerated. Limitation: The number of patients studied and the trial duration were insufficient to warrant recommending the use of salsalate for type 2 diabetes at this time. Conclusion: Salsalate lowers HbA(1c) levels and improves other markers of glycemic control in patients with type 2 diabetes and may therefore provide a new avenue for treatment. Renal and cardiac safety of the drug require further evaluation. C1 [Shoelson, Steven E.] Joslin Diabet Ctr, Boston, MA 02215 USA. Tulane Univ, New Orleans, LA 70118 USA. George Washington Univ, Rockville, MD USA. NIDDKD, Washington, DC USA. RP Shoelson, SE (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM steven.shoelson@joslin.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; National Institutes of Health [U01 DK74556, P50 HL83813]; National Institutes of Health General Clinical Research Center; Clinical and Translational Science FX National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.; By National Institutes of Health grants U01 DK74556 and P50 HL83813, National Institutes of Health General Clinical Research Center and Clinical and Translational Science Award grants at multiple sites, and the Tullis-Tulane (Dr. Fonseca) and Helen and Morton Adler (Dr. Shoelson) Chairs. Caraco Pharmaceuticals (Detroit, Michigan) supplied drug and placebo, Lifescan (Miltipas, California; a division of Johnson & Johnson) supplied home glucose-monitoring kits, and Mercodia (Uppsala, Sweden) supplied insulin assay kits. NR 37 TC 198 Z9 201 U1 0 U2 13 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 MAR 16 PY 2010 VL 152 IS 6 BP 346 EP + DI 10.7326/0003-4819-152-6-201003160-00004 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 573IF UT WOS:000275905200002 PM 20231565 ER PT J AU Halpern, SD Raz, A Kohn, R Rey, M Asch, DA Reese, P AF Halpern, Scott D. Raz, Amelie Kohn, Rachel Rey, Michael Asch, David A. Reese, Peter TI Regulated Payments for Living Kidney Donation: An Empirical Assessment of the Ethical Concerns SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ORGAN DONATION; CONJOINT-ANALYSIS; HEALTH-CARE; CONFIDENCE-INTERVALS; COST-EFFECTIVENESS; CLINICAL-TRIALS; DONORS; INCENTIVES; TRANSPLANTATION; CONSEQUENCES AB Background: Although regulated payments to encourage living kidney donation could reduce morbidity and mortality among patients waiting for a kidney transplant, doing so raises several ethical concerns. Objective: To determine the extent to which the 3 main concerns with paying kidney donors might manifest if a regulated market were created. Design: Cross-sectional study of participants' willingness to donate a kidney in 12 scenarios. Setting: Regional rail and urban trolley lines in Philadelphia County, Philadelphia, Pennsylvania. Participants: Of 550 potential participants, 409 completed the questionnaire (response rate, 74.4%); 342 of these participants were medically eligible to donate. Intervention: Across scenarios, researchers experimentally manipulated the amount of money that participants would receive, the participants' risk for subsequently developing kidney failure themselves, and who would receive the donated kidney. Measurements: The researchers determined whether payment represents an undue inducement by evaluating participants' sensitivity to risk in relation to the payment offered or an unjust inducement by evaluating participants' sensitivity to payment as a function of their annual income. The researchers also evaluated whether introducing payment would hinder altruistic donations by comparing participants' willingness to donate altruistically before versus after the introduction of payments. Results: Generalized estimating equation models revealed that participants' willingness to donate increased significantly as their risk for kidney failure decreased, as the payment offered increased, and when the kidney recipient was a family member rather than a patient on a public waiting list (P < 0.001 for each). No statistical interactions were identified between payment and risk (odds ratio, 1.00 [95% CI, 0.96 to 1.03]) or between payment and income (odds ratio, 1.01 [CI, 0.99 to 1.03]). The proximity of these estimates to 1.0 and narrowness of the CIs suggest that payment is neither an undue nor an unjust inducement, respectively. Alerting participants to the possibility of payment did not alter their willingness to donate for altruistic reasons (P = 0.40). Limitation: Choices revealed in hypothetical scenarios may not reflect real-world behaviors. Conclusion: Theoretical concerns about paying persons for living kidney donation are not corroborated by empirical evidence. A real-world test of regulated payments for kidney donation is needed to definitively show whether payment provides a viable and ethical method to increase the supply of kidneys available for transplantation. C1 [Halpern, Scott D.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Halpern, SD (reprint author), Univ Penn, Sch Med, 724 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM scott.halpern@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU Greenwall Foundation Faculty Scholar Award in Bioethics; National Institutes of Health [K23-078688-01]; University of Pennsylvania Center for Bioethics FX By a Greenwall Foundation Faculty Scholar Award in Bioethics (Dr. Halpern), the National Institutes of Health (Dr. Reese; grant K23-078688-01), and internships from the University of Pennsylvania Center for Bioethics (Ms. Raz, Ms. Kohn, and Mr. Rey). NR 43 TC 27 Z9 27 U1 1 U2 11 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 MAR 16 PY 2010 VL 152 IS 6 BP 358 EP + DI 10.7326/0003-4819-152-6-201003160-00005 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 573IF UT WOS:000275905200003 PM 20231566 ER PT J AU Sboner, A Demichelis, F Calza, S Pawitan, Y Setlur, SR Hoshida, Y Perner, S Adami, HO Fall, K Mucci, LA Kantoff, PW Stampfer, M Andersson, SO Varenhorst, E Johansson, JE Gerstein, MB Golub, TR Rubin, MA Andren, O AF Sboner, Andrea Demichelis, Francesca Calza, Stefano Pawitan, Yudi Setlur, Sunita R. Hoshida, Yujin Perner, Sven Adami, Hans-Olov Fall, Katja Mucci, Lorelei A. Kantoff, Philip W. Stampfer, Meir Andersson, Swen-Olof Varenhorst, Eberhard Johansson, Jan-Erik Gerstein, Mark B. Golub, Todd R. Rubin, Mark A. Andren, Ove TI Molecular sampling of prostate cancer: a dilemma for predicting disease progression SO BMC MEDICAL GENOMICS LA English DT Article ID TMPRSS2-ERG GENE FUSION; CIRCULATING TUMOR-CELLS; POPULATION-BASED COHORT; RADICAL PROSTATECTOMY; INTEROBSERVER REPRODUCIBILITY; INTRAEPITHELIAL NEOPLASIA; CLINICAL-IMPLICATIONS; SYSTEMIC PROGRESSION; TISSUE MICROARRAYS; TRANSITION ZONE AB Background: Current prostate cancer prognostic models are based on pre-treatment prostate specific antigen (PSA) levels, biopsy Gleason score, and clinical staging but in practice are inadequate to accurately predict disease progression. Hence, we sought to develop a molecular panel for prostate cancer progression by reasoning that molecular profiles might further improve current clinical models. Methods: We analyzed a Swedish Watchful Waiting cohort with up to 30 years of clinical follow up using a novel method for gene expression profiling. This cDNA-mediated annealing, selection, ligation, and extension (DASL) method enabled the use of formalin-fixed paraffin-embedded transurethral resection of prostate (TURP) samples taken at the time of the initial diagnosis. We determined the expression profiles of 6100 genes for 281 men divided in two extreme groups: men who died of prostate cancer and men who survived more than 10 years without metastases (lethals and indolents, respectively). Several statistical and machine learning models using clinical and molecular features were evaluated for their ability to distinguish lethal from indolent cases. Results: Surprisingly, none of the predictive models using molecular profiles significantly improved over models using clinical variables only. Additional computational analysis confirmed that molecular heterogeneity within both the lethal and indolent classes is widespread in prostate cancer as compared to other types of tumors. Conclusions: The determination of the molecularly dominant tumor nodule may be limited by sampling at time of initial diagnosis, may not be present at time of initial diagnosis, or may occur as the disease progresses making the development of molecular biomarkers for prostate cancer progression challenging. C1 [Demichelis, Francesca; Perner, Sven; Rubin, Mark A.] Weill Cornell Med Ctr, Dept Pathol & Lab Med, New York, NY USA. [Sboner, Andrea; Gerstein, Mark B.] Yale Univ, Dept Biochem & Mol Biophys, New Haven, CT 06520 USA. [Demichelis, Francesca] Weill Cornell Med Ctr, Inst Computat Biomed, New York, NY USA. [Calza, Stefano; Pawitan, Yudi; Adami, Hans-Olov; Fall, Katja] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Calza, Stefano] Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy. [Setlur, Sunita R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Hoshida, Yujin; Kantoff, Philip W.; Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Adami, Hans-Olov; Fall, Katja; Mucci, Lorelei A.; Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Andersson, Swen-Olof; Johansson, Jan-Erik; Andren, Ove] Orebro Univ Hosp, Dept Urol, SE-70185 Orebro, Sweden. [Mucci, Lorelei A.; Kantoff, Philip W.; Stampfer, Meir] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mucci, Lorelei A.; Stampfer, Meir] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Varenhorst, Eberhard] Linkoping Univ Hosp, Dept Urol, SE-58185 Linkoping, Sweden. [Gerstein, Mark B.] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. [Golub, Todd R.] Broad Inst MIT & Harvard, Howard Hughes Med Inst, Cambridge, MA 02142 USA. RP Rubin, MA (reprint author), Weill Cornell Med Ctr, Dept Pathol & Lab Med, New York, NY USA. EM asbmgmr@gersteinlab.org RI Fall, Katja/A-9186-2012; Calza, Stefano/B-1915-2010; OI Calza, Stefano/0000-0003-4996-7995; Sboner, Andrea/0000-0001-6915-3070; Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631; Fall, Katja/0000-0002-3649-2639 FU National Cancer Institute (NCI) [P50 90381]; Dana Farber/Harvard Cancer Center Prostate S.P.O.R.E; National Institute of Health (NIH) [RR19895] FX We would like to acknowledge the National Cancer Institute (NCI) grant P50 90381 support for the Dana Farber/Harvard Cancer Center Prostate S.P.O.R.E. and the National Institute of Health (NIH) grant RR19895 for the Yale University Biomedical High Performance Computing Center. NR 55 TC 86 Z9 86 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD MAR 16 PY 2010 VL 3 AR 8 DI 10.1186/1755-8794-3-8 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 585SA UT WOS:000276848100001 PM 20233430 ER PT J AU Sheng, Q Liu, XG Fleming, E Yuan, K Piao, HY Chen, JY Moustafa, Z Thomas, RK Greulich, H Schinzel, A Zaghlul, S Batt, D Ettenberg, S Meyerson, M Schoeberl, B Kung, AL Hahn, WC Drapkin, R Livingston, DM Liu, JF AF Sheng, Qing Liu, Xinggang Fleming, Eleanor Yuan, Karen Piao, Huiying Chen, Jinyun Moustafa, Zeinab Thomas, Roman K. Greulich, Heidi Schinzel, Anna Zaghlul, Sara Batt, David Ettenberg, Seth Meyerson, Matthew Schoeberl, Birgit Kung, Andrew L. Hahn, William C. Drapkin, Ronny Livingston, David M. Liu, Joyce F. TI An Activated ErbB3/NRG1 Autocrine Loop Supports In Vivo Proliferation in Ovarian Cancer Cells SO CANCER CELL LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; PHASE-II TRIAL; ONCOGENE ADDICTION; PHOSPHATIDYLINOSITOL 3-KINASE; MONOCLONAL-ANTIBODY; LUNG-CANCER; EXPRESSION; RECEPTOR; THERAPY; CARCINOMA AB Ovarian cancer is a leading cause of death from gynecologic malignancies. Treatment for advanced-stage disease remains limited and, to date, targeted therapies have been incompletely explored. By systematically suppressing each human tyrosine kinase in ovarian cancer cell lines by RNAi, we found that an autocrine signal-transducing loop involving NRG1 and activated ErbB3 operates in a subset of primary ovarian cancers and ovarian cancer cell lines. Perturbation of this circuit with ErbB3-directed RNAi decreased cell growth in three-dimensional culture and resulted in decreased disease progression and prolonged survival in a xenograft mouse model of ovarian cancer. Furthermore, a monoclonal ErbB3-directed antibody (MM-121) also significantly inhibited tumor growth in vivo. These findings identify ErbB3 as a potential therapeutic target in ovarian cancer. C1 [Sheng, Qing; Liu, Xinggang; Fleming, Eleanor; Yuan, Karen; Zaghlul, Sara; Livingston, David M.; Liu, Joyce F.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Piao, Huiying; Greulich, Heidi; Schinzel, Anna; Meyerson, Matthew; Hahn, William C.; Drapkin, Ronny; Liu, Joyce F.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sheng, Qing; Liu, Xinggang; Fleming, Eleanor; Yuan, Karen; Piao, Huiying; Greulich, Heidi; Schinzel, Anna; Zaghlul, Sara; Meyerson, Matthew; Kung, Andrew L.; Hahn, William C.; Drapkin, Ronny; Livingston, David M.; Liu, Joyce F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Piao, Huiying; Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Greulich, Heidi] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Chen, Jinyun; Moustafa, Zeinab; Batt, David; Ettenberg, Seth] Novartis Oncol, Cambridge, MA 02139 USA. [Thomas, Roman K.] Univ Cologne, Fac Med, D-50931 Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Max Planck Soc, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, D-50931 Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Dept Internal Med 1, D-50937 Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol, D-50937 Cologne, Germany. [Thomas, Roman K.] Max Planck Soc, Chem Genom Ctr, D-44227 Dortmund, Germany. [Greulich, Heidi; Schinzel, Anna; Meyerson, Matthew; Hahn, William C.] MIT, Cambridge, MA 02142 USA. [Greulich, Heidi; Schinzel, Anna; Meyerson, Matthew; Hahn, William C.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. [Schoeberl, Birgit] Merrimack Pharmaceut, Cambridge, MA 02139 USA. [Kung, Andrew L.] Childrens Hosp, Boston, MA 02115 USA. [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM david_livingston@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Drapkin, Ronny/E-9944-2016; OI Drapkin, Ronny/0000-0002-6912-6977; Kung, Andrew/0000-0002-9091-488X FU NIH [U54CA112962, W81XWH-07-0408, R33CA128625, K12CA08772307, P50-CA105009, K08CA108748]; DFCI; Ovarian Cancer Research Fund; ASCO Young Investigator Award and Prevent Cancer Foundation; Deborah and Robert First; Joel and Randi Cutler Ovarian Research Fund; Aaron Foundation FX We thank R. Wright and B. Ospina for expert technical assistance in mouse imaging. We would also like to thank Dr. S. Mok for providing human ovarian surface epithelial cells. This work was supported by NIH grants U54CA112962 (W.C.H.), W81XWH-07-0408 (W.C.H.), R33CA128625 (W.C.H.), and K12CA08772307 (J.F.L.); by NCI grants P50-CA105009 SPORE in Ovarian Cancer (Q.S., R.D.) and K08CA108748 (R.D.); by the DFCI/Novartis Program in Drug Discovery; by generous funding from the Women's Cancer Programs of DFCI; from the Ovarian Cancer Research Fund (R.D.); from the ASCO Young Investigator Award and Prevent Cancer Foundation (J.F.L.); from Deborah and Robert First (D.M.L., R.D.); the Joel and Randi Cutler Ovarian Research Fund (R.D.); and from the Aaron Foundation (D.M.L.). D.M.L., W.C.H., R.D., M.M., and A.L.K. are grantees of and consultants to the Novartis Institute of Biomedical Research. J.C., Z.M., D.B., and S.E. are employees and shareholders of the Novartis Institute of Biomedical Research. B.S. is an employee and shareholder of Merrimack Pharmaceuticals. NR 44 TC 112 Z9 115 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR 16 PY 2010 VL 17 IS 3 BP 298 EP 310 DI 10.1016/j.ccr.2009.12.047 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 572CK UT WOS:000275804200011 PM 20227043 ER PT J AU Gianni, D Li, AR Tesco, G Mckay, KM Moore, J Raygor, K Rota, M Gwathmey, JK Dec, GW Aretz, T Leri, A Semigran, MJ Anversa, P Macgillivray, TE Tanzi, RE del Monte, F AF Gianni, Davide Li, Airong Tesco, Giuseppina Mckay, Kenneth M. Moore, John Raygor, Kunal Rota, Marcello Gwathmey, Judith K. Dec, G. William Aretz, Thomas Leri, Annarosa Semigran, Marc J. Anversa, Piero Macgillivray, Thomas E. Tanzi, Rudolph E. del Monte, Federica TI Protein Aggregates and Novel Presenilin Gene Variants in Idiopathic Dilated Cardiomyopathy SO CIRCULATION LA English DT Article DE calcium; cardiomyopathy; genetics; heart failure; myocytes ID SOLUBLE AMYLOID OLIGOMERS; ALZHEIMERS-DISEASE; HEART-FAILURE; MUTATIONS; CALCIUM; CELL; ACCUMULATION; POPULATION; MECHANISM; FREQUENCY AB Background-Heart failure is a debilitating condition resulting in severe disability and death. In a subset of cases, clustered as idiopathic dilated cardiomyopathy (iDCM), the origin of heart failure is unknown. In the brain of patients with dementia, proteinaceous aggregates and abnormal oligomeric assemblies of beta-amyloid impair cell function and lead to cell death. Methods and Results-We have similarly characterized fibrillar and oligomeric assemblies in the hearts of iDCM patients, pointing to abnormal protein aggregation as a determinant of iDCM. We also showed that oligomers alter myocyte Ca2+ homeostasis. Additionally, we have identified 2 new sequence variants in the presenilin-1 (PSEN1) gene promoter leading to reduced gene and protein expression. We also show that presenilin-1 coimmunoprecipitates with SERCA2a. Conclusions-On the basis of these findings, we propose that 2 mechanisms may link protein aggregation and cardiac function: oligomer-induced changes on Ca2+ handling and a direct effect of PSEN1 sequence variants on excitation-contraction coupling protein function. (Circulation. 2010; 121: 1216-1226.) C1 [Gianni, Davide; Gwathmey, Judith K.; del Monte, Federica] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02125 USA. [Li, Airong; Tesco, Giuseppina; Mckay, Kenneth M.; Moore, John; Raygor, Kunal; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Genet & Aging Res Unit, Boston, MA 02114 USA. [Aretz, Thomas] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dec, G. William; Semigran, Marc J.] Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. [Macgillivray, Thomas E.] Massachusetts Gen Hosp, Cardiac Surg Div, Boston, MA 02114 USA. [Rota, Marcello; Leri, Annarosa; Anversa, Piero] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Rota, Marcello; Leri, Annarosa; Anversa, Piero] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP del Monte, F (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02125 USA. EM tanzi@helix.harvard.edu; fdelmont@bidmc.harvard.edu FU National Institutes of Health [K08-HL69842, R01AG014713, R01MH60009]; Beth Israel Deaconess Medical Center discretional funds; Cure Alzheimer's fund; Neuroscience Education and Research Foundation FX This work was supported by funds from the National Institutes of Health (K08-HL69842 to Dr del Monte, R01AG014713, R01MH60009 to Dr Tanzi), Beth Israel Deaconess Medical Center discretional funds (to Dr del Monte), the Cure Alzheimer's fund ( to Dr Tanzi), and the Neuroscience Education and Research Foundation (to Dr Li). NR 42 TC 33 Z9 33 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR 16 PY 2010 VL 121 IS 10 BP 1216 EP U81 DI 10.1161/CIRCULATIONAHA.109.879510 PG 15 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 569NQ UT WOS:000275604400008 PM 20194882 ER PT J AU Januzzi, JL Bamberg, F Lee, H Truong, QA Nichols, JH Karakas, M Mohammed, AA Schlett, CL Nagurney, JT Hoffmann, U Koenig, W AF Januzzi, James L., Jr. Bamberg, Fabian Lee, Hang Truong, Quynh A. Nichols, John H. Karakas, Mahir Mohammed, Asim A. Schlett, Christopher L. Nagurney, John T. Hoffmann, Udo Koenig, Wolfgang TI High-Sensitivity Troponin T Concentrations in Acute Chest Pain Patients Evaluated With Cardiac Computed Tomography SO CIRCULATION LA English DT Article DE myocardial infarction; troponin; diagnosis; imaging ID ACUTE CORONARY SYNDROME; ACUTE MYOCARDIAL-INFARCTION; I ASSAY; EARLY-DIAGNOSIS; ADVERSE EVENTS; HEART-FAILURE; ISCHEMIA; RISK; PREDICTION; ELEVATION AB Background-For evaluation of patients with chest pain and suspected acute coronary syndrome (ACS), consensus guidelines recommend use of a cardiac troponin cut point that corresponds to the 99th percentile of a healthy population. Most conventional troponin methods lack sufficient precision at this low level. Methods and Results-In a cross-sectional study, 377 patients (mean age 53.7 years, 64.2% male) with chest pain and low to intermediate likelihood for ACS were enrolled in the emergency department. Blood was tested with a precommercial high-sensitivity troponin T assay (hsTnT) and compared with a conventional cardiac troponin T method. Patients underwent a 64-slice coronary computed tomography coronary angiogram at the time of phlebotomy, on average 4 hours from initial presentation. Among patients with acute chest pain, 37 (9.8%) had an ACS. Using the 99th percentile cut point for a healthy population (13 pg/mL), hsTnT had 62% sensitivity, 89% specificity, 38% positive predictive value, and 96% negative predictive value for ACS. Compared with the cardiac troponin T method, hsTnT detected 27% more ACS cases (P=.001), and an hsTnT above the 99th percentile strongly predicted ACS (odds ratio 9.0, 95% confidence interval 3.9 to 20.9, P<0.001). Independent of ACS diagnosis, computed tomography angiography demonstrated that concentrations of hsTnT were determined by numerous factors, including the presence and severity of coronary artery disease, left ventricular mass, left ventricular ejection fraction, and regional left ventricular dysfunction. Conclusions-Among low-to intermediate-risk patients with chest pain, hsTnT provides good sensitivity and specificity for ACS. Elevation of hsTnT identifies patients with myocardial injury and significant structural heart disease, irrespective of the diagnosis of ACS. (Circulation. 2010; 121: 1227-1234.) C1 [Bamberg, Fabian; Truong, Quynh A.; Nichols, John H.; Schlett, Christopher L.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA. [Januzzi, James L., Jr.; Truong, Quynh A.; Mohammed, Asim A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Karakas, Mahir; Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med & Cardiol 2, Ulm, Germany. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, 165 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org FU National Institutes of Health [RO1 HL080053, T32HL076136, L30HL093896]; Dennis and Marilyn Barry Cardiology Fellowship; German Federal Ministry of Education and Research; Foundation of German Business FX This study was sponsored in part by the National Institutes of Health (RO1 HL080053). Dr Januzzi is supported in part by the Balson Scholar Fund. Dr Truong is supported by National Institutes of Health grants T32HL076136 and L30HL093896. Dr Mohammed is supported by the Dennis and Marilyn Barry Cardiology Fellowship, and Mr Schlett is supported in part by grants from the German Federal Ministry of Education and Research, as well as the Foundation of German Business. NR 25 TC 117 Z9 118 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 16 PY 2010 VL 121 IS 10 BP 1227 EP U91 DI 10.1161/CIRCULATIONAHA.109.893826 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 569NQ UT WOS:000275604400009 PM 20194879 ER PT J AU Samuel, SM Thirunavukkarasu, M Penumathsa, SV Koneru, S Zhan, LJ Maulik, G Sudhakaran, PR Maulik, N AF Samuel, Samson Mathews Thirunavukkarasu, Mahesh Penumathsa, Suresh Varma Koneru, Srikanth Zhan, Lijun Maulik, Gautam Sudhakaran, Perumana R. Maulik, Nilanjana TI Thioredoxin-1 Gene Therapy Enhances Angiogenic Signaling and Reduces Ventricular Remodeling in Infarcted Myocardium of Diabetic Rats SO CIRCULATION LA English DT Article DE myocardial infarction; diabetes mellitus; angiogenesis; oxidative stress; thioredoxins; gene therapy; echocardiograpy ID ENDOTHELIAL GROWTH-FACTOR; HEME OXYGENASE-1; OXIDATIVE STRESS; CARDIOMYOCYTE APOPTOSIS; MAMMALIAN THIOREDOXIN; REACTIVE OXYGEN; NITRIC-OXIDE; MAP-KINASE; NEOVASCULARIZATION; EXPRESSION AB Background-The present study evaluated the reversal of diabetes-mediated impairment of angiogenesis in a myocardial infarction model of type 1 diabetic rats by intramyocardial administration of an adenoviral vector encoding thioredoxin-1 (Ad.Trx1). Various studies have linked diabetes-mediated impairment of angiogenesis to dysfunctional antioxidant systems in which thioredoxin-1 plays a central role. Methods and Results-Ad.Trx1 was administered intramyocardially in nondiabetic and diabetic rats immediately after myocardial infarction. Ad. LacZ was similarly administered to the respective control groups. The hearts were excised for molecular and immunohistochemical analysis at predetermined time points. Myocardial function was measured by echocardiography 30 days after the intervention. The Ad.Trx1-administered group exhibited reduced fibrosis, oxidative stress, and cardiomyocyte and endothelial cell apoptosis compared with the diabetic myocardial infarction group, along with increased capillary and arteriolar density. Western blot and immunohistochemical analysis demonstrated myocardial overexpression of thioredoxin-1, heme oxygenase-1, vascular endothelial growth factor, and p38 mitogen-activated protein kinase-beta, as well as decreased phosphorylated JNK and p38 mitogen-activated protein kinase-alpha, in the Ad.Trx1-treated diabetic group. Conversely, we observed a significant reduction in the expression of vascular endothelial growth factor in nondiabetic and diabetic animals treated with tin protoporphyrin (SnPP, a heme oxygenase-1 enzyme inhibitor), even after Ad.Trx1 therapy. Echocardiographic analysis after 4 weeks of myocardial infarction revealed significant improvement in myocardial functional parameters such as ejection fraction, fractional shortening, and E/A ratio in the Ad.Trx1-administered group compared with the diabetic myocardial infarction group. Conclusions-This study demonstrates for the first time that impairment of angiogenesis and myocardial dysfunction can be regulated by Ad.Trx1 gene therapy in streptozotocin-induced diabetic rats subjected to infarction. (Circulation. 2010; 121: 1244-1255.) C1 [Samuel, Samson Mathews; Thirunavukkarasu, Mahesh; Penumathsa, Suresh Varma; Koneru, Srikanth; Zhan, Lijun; Maulik, Nilanjana] Univ Connecticut, Ctr Hlth, Mol Cardiol & Angiogenesis Lab, Dept Surg, Farmington, CT 06030 USA. [Samuel, Samson Mathews; Sudhakaran, Perumana R.] Univ Kerala, Dept Biochem, Trivandrum 695581, Kerala, India. [Maulik, Gautam] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Maulik, N (reprint author), Univ Connecticut, Ctr Hlth, Mol Cardiol & Angiogenesis Lab, Dept Surg, 263 Farmington Ave, Farmington, CT 06030 USA. EM nmaulik@neuron.uchc.edu FU National Institutes of Health [HL-56803, HL-69910] FX This study was supported by National Institutes of Health grants HL-56803 and HL-69910 to Dr Maulik. NR 40 TC 57 Z9 61 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 16 PY 2010 VL 121 IS 10 BP 1244 EP U129 DI 10.1161/CIRCULATIONAHA.109.872481 PG 27 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 569NQ UT WOS:000275604400011 PM 20194885 ER PT J AU van Kimmenade, RRJ Crijns, HJGM Januzzi, JL AF van Kimmenade, Roland R. J. Crijns, Harry J. G. M. Januzzi, James L. TI Letter by van Kimmenade et al Regarding Article, "Urinary N-Terminal Prohormone Brain Natriuretic Peptide Excretion in Patients With Chronic Heart Failure" SO CIRCULATION LA English DT Letter ID TRANSPORT; PROTEINS C1 [van Kimmenade, Roland R. J.; Crijns, Harry J. G. M.] Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherlands. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP van Kimmenade, RRJ (reprint author), Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherlands. RI Kimmenade, R.R.J./L-4432-2015 NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 16 PY 2010 VL 121 IS 10 BP E242 EP E242 DI 10.1161/CIR.0b013e3181d78116 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 569NQ UT WOS:000275604400018 PM 20231541 ER PT J AU Deo, AJ Costa, R DeLisi, LE DeSalle, R Haghighi, F AF Deo, Anthony J. Costa, Ramiro DeLisi, Lynn E. DeSalle, Rob Haghighi, Fatemeh TI A Novel Analytical Framework for Dissecting the Genetic Architecture of Behavioral Symptoms in Neuropsychiatric Disorders SO PLOS ONE LA English DT Article ID GENOME-WIDE SCAN; SCHIZOAFFECTIVE DISORDER; DEPRESSIVE-DISORDERS; MAJOR DEPRESSION; BIPOLAR-DISORDER; LINKAGE ANALYSIS; EARLY-ONSET; SCHIZOPHRENIA SUSCEPTIBILITY; PSYCHIATRIC-DISORDERS; LOCI AB Background: For diagnosis of neuropsychiatric disorders, a categorical classification system is often utilized as a simple way for conceptualizing an often complex clinical picture. This approach provides an unsatisfactory model of mental illness, since in practice patients do not conform to these prototypical diagnostic categories. Family studies show notable familial co-aggregation between schizophrenia and bipolar illness and between schizoaffective disorders and both bipolar disorder and schizophrenia, revealing that mental illness does not conform to such categorical models and is likely to follow a continuum encompassing a spectrum of behavioral symptoms. Results and Methodology: We introduce an analytic framework to dissect the phenotypic heterogeneity present in complex psychiatric disorders based on the conceptual paradigm of a continuum of psychosis. The approach identifies subgroups of behavioral symptoms that are likely to be phenotypically and genetically homogenous. We have evaluated this approach through analysis of simulated data with simulated behavioral traits and predisposing genetic factors. We also apply this approach to a psychiatric dataset of a genome scan for schizophrenia for which extensive behavioral information was collected for each individual patient and their families. With this approach, we identified significant evidence for linkage among depressed individuals with two distinct symptom profiles, that is individuals with sleep disturbance symptoms with linkage on chromosome 2q13 and also a mutually exclusive group of individuals with symptoms of concentration problems with linkage on chromosome 2q35. In addition we identified a subset of individuals with schizophrenia defined by language disturbances with linkage to chromosome 2p25.1 and a group of patients with a phenotype intermediate between those of schizophrenia and schizoaffective disorder with linkage to chromosome 2p21. Conclusions: The findings presented are novel and demonstrate the efficacy of this approach in detection of genes underlying such complex human disorders as schizophrenia and depression. C1 [Deo, Anthony J.] NYU, Dept Biol, New York, NY 10003 USA. [Deo, Anthony J.; DeSalle, Rob] Amer Museum Nat Hist, Ctr Comparat Genom, New York, NY 10024 USA. [Deo, Anthony J.; DeSalle, Rob] Amer Museum Nat Hist, Dept Invertebrate Zool, New York, NY 10024 USA. [Deo, Anthony J.; Haghighi, Fatemeh] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Costa, Ramiro; Haghighi, Fatemeh] New York State Psychiat Inst & Hosp, Div Mol Imaging & Neuropathol, New York, NY 10032 USA. [DeLisi, Lynn E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. RP Deo, AJ (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. EM fgh3@columbia.edu FU NSF [DEB0508584]; National Science Foundation; [HG002915]; [MH074118] FX This work was supported by HG002915, MH074118, and NSF DEB0508584. The analyses were conducted on computing resources supported by the National Science Foundation under the following NSF programs: Partnerships for Advanced Computational Infrastructure, Distributed Terascale Facility (DTF) and Terascale Extensions: Enhancements to the Extensible Terascale Facility. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 5 Z9 5 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 MAR 16 PY 2010 VL 5 IS 3 AR e9714 DI 10.1371/journal.pone.0009714 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 570ZC UT WOS:000275716400012 PM 20300526 ER PT J AU Zhou, YB Ramachandran, S Oh-hora, M Rao, A Hogan, PG AF Zhou, Yubin Ramachandran, Sweta Oh-hora, Masatsugu Rao, Anjana Hogan, Patrick G. TI Pore architecture of the ORAI1 store-operated calcium channel SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cross-linking; membrane protein; store-operated calcium entry; stromal interaction molecule; structure ID ACTIVATES CRAC CHANNELS; DISULFIDE CROSS-LINKING; PLASMA-MEMBRANE; CA2+ ENTRY; BACTERIAL CHEMORECEPTOR; TRANSMEMBRANE DOMAIN; PROTEIN-STRUCTURE; ION PERMEATION; MICE LACKING; STIM1 AB ORAI1 is the pore-forming subunit of the calcium release-activated calcium (CRAC) channel, a store-operated channel that is central to Ca(2+) signaling in mammalian cells. Electrophysiological data have shown that the acidic residues E106 in transmembrane helix 1 (TM1) and E190 in TM3 contribute to the high selectivity of ORAI1 channels for Ca(2+). We have examined the pore architecture of the ORAI1 channel using ORAI1 proteins engineered to contain either one or two cysteine residues. Disulfide cross-linking shows that ORAI1 assembles as a tetramer or a higher oligomer with TM1 centrally located. Cysteine side chains projecting from TM1 at position 88, 95, 102, or 106 cross-link efficiently to the corresponding side chain in a second ORAI1 monomer. Cysteine residues at position 190 or at surrounding positions in TM3 do not cross-link. We conclude that E106 residues in wild-type ORAI1 are positioned to form a Ca(2+) binding site in the channel pore and that E190 interacts less directly with ions traversing the pore. The cross-linking data further identify a relatively rigid segment of TM1 adjacent to E106 that is likely to contribute to the selectivity filter. C1 [Zhou, Yubin; Ramachandran, Sweta; Oh-hora, Masatsugu; Rao, Anjana; Hogan, Patrick G.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Zhou, Yubin; Ramachandran, Sweta; Oh-hora, Masatsugu; Rao, Anjana; Hogan, Patrick G.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Zhou, Yubin; Oh-hora, Masatsugu; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hogan, PG (reprint author), Childrens Hosp, Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM hogan@idi.harvard.edu RI Zhou, Yubin/D-4748-2011 OI Zhou, Yubin/0000-0001-7962-0517 FU NIH [AI84167, AI40127]; Cancer Research Institute; Leukemia and Lymphoma Society FX This work was funded by NIH grants AI84167 and AI40127 (to A. R. and P. G. H.). Y.Z. was supported by an Irvington Fellowship from the Cancer Research Institute and a postdoctoral fellowship from the Leukemia and Lymphoma Society. NR 43 TC 69 Z9 70 U1 2 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 MAR 16 PY 2010 VL 107 IS 11 BP 4896 EP 4901 DI 10.1073/pnas.1001169107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 570YI UT WOS:000275714300020 PM 20194792 ER PT J AU Vallet, S Mukherjee, S Vaghela, N Hideshima, T Fulciniti, M Pozzi, S Santo, L Cirstea, D Patel, K Sohani, AR Guimaraes, A Xie, WL Chauhan, D Schoonmaker, JA Attar, E Churchill, M Weller, E Munshi, N Seehra, JS Weissleder, R Anderson, KC Scadden, DT Raje, N AF Vallet, Sonia Mukherjee, Siddhartha Vaghela, Nileshwari Hideshima, Teru Fulciniti, Mariateresa Pozzi, Samantha Santo, Loredana Cirstea, Diana Patel, Kishan Sohani, Aliyah R. Guimaraes, Alex Xie, Wanling Chauhan, Dharminder Schoonmaker, Jesse A. Attar, Eyal Churchill, Michael Weller, Edie Munshi, Nikhil Seehra, Jasbir S. Weissleder, Ralph Anderson, Kenneth C. Scadden, David T. Raje, Noopur TI Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE osteoblasts; osteoclasts; tumor niche ID MARROW STROMAL CELLS; OSTEOBLAST DIFFERENTIATION; IN-VIVO; MODEL; INHIBIN; SYSTEM; BETA; DLX5; OSTEOCLASTOGENESIS; SUPPRESSION AB Understanding the pathogenesis of cancer-related bone disease is crucial to the discovery of new therapies. Here we identify activin A, a TGF-beta family member, as a therapeutically amenable target exploited by multiple myeloma (MM) to alter its microenvironmental niche favoring osteolysis. Increased bone marrow plasma activin A levels were found in MM patients with osteolytic disease. MM cell engagement of marrow stromal cells enhanced activin A secretion via adhesion-mediated JNK activation. Activin A, in turn, inhibited osteoblast differentiation via SMAD2-dependent distalless homeobox-5 down-regulation. Targeting activin A by a soluble decoy receptor reversed osteoblast inhibition, ameliorated MM bone disease, and inhibited tumor growth in an in vivo humanized MM model, setting the stage for testing in human clinical trials. C1 [Vallet, Sonia; Vaghela, Nileshwari; Pozzi, Samantha; Patel, Kishan; Sohani, Aliyah R.; Attar, Eyal; Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA 02114 USA. [Mukherjee, Siddhartha; Schoonmaker, Jesse A.; Churchill, Michael; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, MGH Ctr Regenerat Med, Cambridge, MA 02138 USA. [Hideshima, Teru; Fulciniti, Mariateresa; Santo, Loredana; Cirstea, Diana; Chauhan, Dharminder; Munshi, Nikhil; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fulciniti, Mariateresa; Munshi, Nikhil] Vet Affairs Boston Hlth Care Syst, Dept Med, Boston, MA 02130 USA. [Guimaraes, Alex; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Simches Res Facil, Boston, MA 02114 USA. [Xie, Wanling; Weller, Edie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Seehra, Jasbir S.] Acceleron Pharma, Cambridge, MA 02139 USA. RP Raje, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA 02114 USA. EM nraje@partners.org RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 FU International Myeloma Foundation [K08]; NIH; ASCO CDA; MMRF; LLS CDA; NIH SPORE FX Grant support for this study was received in the form of an International Myeloma Foundation junior award (S.V., L.S., S.P.), K08 (S.M.), NIH (D.T.S.), ASCO CDA, MMRF, LLS CDA, and NIH SPORE (N.R.). NR 31 TC 92 Z9 94 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 16 PY 2010 VL 107 IS 11 BP 5124 EP 5129 DI 10.1073/pnas.0911929107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 570YI UT WOS:000275714300059 PM 20194748 ER PT J AU Westreich, D Cole, SR Tien, PC Chmiel, JS Kingsley, L Funk, MJ Anastos, K Jacobson, LP AF Westreich, Daniel Cole, Stephen R. Tien, Phyllis C. Chmiel, Joan S. Kingsley, Lawrence Funk, Michele Jonsson Anastos, Kathryn Jacobson, Lisa P. TI Time Scale and Adjusted Survival Curves for Marginal Structural Cox Models SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE acquired immunodeficiency syndrome; antiretroviral therapy; highly active; bias (epidemiology); causal inference; confounding factors (epidemiology); proportional hazards model; survival curve; survival time ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; INVERSE PROBABILITY WEIGHTS; LOGISTIC-REGRESSION; CAUSAL INFERENCE; HIV; AIDS; MORTALITY; CHOICE; DEATH AB Typical applications of marginal structural time-to-event (e.g., Cox) models have used time on study as the time scale. Here, the authors illustrate use of time on treatment as an alternative time scale. In addition, a method is provided for estimating Kaplan-Meier-type survival curves for marginal structural models. For illustration, the authors estimate the total effect of highly active antiretroviral therapy on time to acquired immunodeficiency syndrome (AIDS) or death in 1,498 US men and women infected with human immunodeficiency virus and followed for 6,556 person-years between 1995 and 2002; 323 incident cases of clinical AIDS and 59 deaths occurred. Of the remaining 1,116 participants, 77% were still under observation at the end of follow-up. By using time on study, the hazard ratio for AIDS or death comparing always with never using highly active antiretroviral therapy from the marginal structural model was 0.52 (95% confidence interval: 0.35, 0.76). By using time on treatment, the analogous hazard ratio was 0.44 (95% confidence interval: 0.32, 0.60). In time-to-event analyses, the choice of time scale may have a meaningful impact on estimates of association and precision. In the present example, use of time on treatment yielded a hazard ratio further from the null and more precise than use of time on study as the time scale. C1 [Westreich, Daniel; Cole, Stephen R.; Funk, Michele Jonsson] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Chmiel, Joan S.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Kingsley, Lawrence] Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA USA. [Anastos, Kathryn] Montefiore Med Ctr, Bronx, NY 10467 USA. [Anastos, Kathryn] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Jacobson, Lisa P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Cole, SR (reprint author), McGavran Greenberg Hall,CB7435, Chapel Hill, NC 27599 USA. EM cole@unc.edu RI Jonsson Funk, Michele/F-6885-2011 OI Jonsson Funk, Michele/0000-0002-3756-7540 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [T32-AI-07001, R03-AI-071763, R01-AA-01759, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Cancer Institute; National Heart, Lung, and Blood Institute [UO1-AI-35042, 5-MO1-RR-00722, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources [UL1 RR024131] FX This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant T32-AI-07001 to D. W.; R03-AI-071763 and R01-AA-01759 to S. R. C.). Data in this article were collected by the Multicenter AIDS Cohort Study (MACS) funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute and the National Heart, Lung, and Blood Institute (UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041). Data in this article were also collected by the Women's Interagency HIV Study Collaborative Study Group funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632). The Women's Interagency HIV Study is jointly funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI grant UL1 RR024131). NR 41 TC 25 Z9 25 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2010 VL 171 IS 6 BP 691 EP 700 DI 10.1093/aje/kwp418 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 568ZJ UT WOS:000275565100009 PM 20139124 ER PT J AU Gradus, JL Qin, P Lincoln, AK Miller, M Lawler, E Sorensen, HT Lash, TL AF Gradus, Jaimie L. Qin, Ping Lincoln, Alisa K. Miller, Matthew Lawler, Elizabeth Sorensen, Henrik Toft Lash, Timothy L. TI Posttraumatic Stress Disorder and Completed Suicide SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; stress disorders; post-traumatic; suicide ID ANXIETY DISORDERS; MAJOR DEPRESSION; REGISTER; RISK; ASSOCIATION; BEHAVIOR; SCHIZOPHRENIA; DIAGNOSES; MORTALITY; VALIDITY AB Most research regarding posttraumatic stress disorder (PTSD) and suicide has focused on suicidal ideation or attempts; no known study of the association between PTSD and completed suicide in a population-based sample has been reported. This study examined the association between PTSD and completed suicide in a population-based sample. Data were obtained from the nationwide Danish health and administrative registries, which include data on all 5.4 million residents of Denmark. All suicides between January 1, 1994, and December 31, 2006, were included, and controls were selected from a sample of all Danish residents. Using this nested case-control design, the authors examined 9,612 suicide cases and 199,306 controls matched to cases on gender, date of birth, and time. Thirty-eight suicide cases (0.40%) and 95 controls (0.05%) were diagnosed with PTSD. The odds ratio associating PTSD with suicide was 9.8 (95% confidence interval: 6.7, 15). The association between PTSD and completed suicide remained after controlling for psychiatric and demographic confounders (odds ratio = 5.3, 95% confidence interval: 3.4, 8.1). Additionally, persons with PTSD and depression had a greater rate of suicide than expected based on their independent effects. In conclusion, a registry-based diagnosis of PTSD based on International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, is a risk factor for completed suicide. C1 [Gradus, Jaimie L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Gradus, Jaimie L.; Sorensen, Henrik Toft; Lash, Timothy L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Qin, Ping] Aarhus Univ, Ctr Registry Based Res, Aarhus, Denmark. [Lincoln, Alisa K.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Lincoln, Alisa K.] Northeastern Univ, Dept Sociol, Boston, MA 02115 USA. [Miller, Matthew] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Lawler, Elizabeth] Harvard Univ, Dept Med, Boston, MA 02115 USA. [Sorensen, Henrik Toft; Lash, Timothy L.] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark. RP Gradus, JL (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM jaimie.gradus@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 NR 30 TC 60 Z9 61 U1 3 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2010 VL 171 IS 6 BP 721 EP 727 DI 10.1093/aje/kwp456 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 568ZJ UT WOS:000275565100012 PM 20160171 ER PT J AU Mularski, RA Campbell, ML Asch, SM Reeve, BB Basch, E Maxwell, TL Hoverman, JR Cuny, J Clauser, SB Snyder, C Seow, H Wu, AW Dy, S AF Mularski, Richard A. Campbell, Margaret L. Asch, Steven M. Reeve, Bryce B. Basch, Ethan Maxwell, Terri L. Hoverman, J. Russell Cuny, Joanne Clauser, Steve B. Snyder, Claire Seow, Hsien Wu, Albert W. Dy, Sydney TI A Review of Quality of Care Evaluation for the Palliation of Dyspnea SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE dyspnea; quality of health care; quality indicators; health care; assessment ID CLINICAL METHODS; LIFE CARE; DISEASE; BREATHLESSNESS; QUESTIONNAIRE; END; INDICATORS; CANCER; DESCRIPTORS; SHORTNESS AB Assessment and management of dyspnea has emerged as a priority topic for quality evaluation and improvement. Evaluating dyspnea quality of care requires valid, reliable, and responsive measures of the care provided to patients across settings and diseases. As part of an Agency for Healthcare Research and Quality Symposium, we reviewed quality of care measures for dyspnea by compiling quality measures identified in systematic searches and reviews. Systematic reviews identified only three existing quality measurement sets that included quality measures for dyspnea care. The existing dyspnea quality measures reported by retrospective evaluations of care assess only four aspects: dyspnea assessment within 48 hours of hospital admission, use of objective scales to rate dyspnea severity, identification of management plans, and evidence of dyspnea reduction. To begin to improve care, clinicians need to assess and regularly document patient's experiences of dyspnea. There is no consensus on how dyspnea should be characterized for quality measurement, and although over 40 tools exist to assess dyspnea, no rating scale or instrument is ideal for palliative care. The panel recommended that dyspnea assessment should include a measure of intensity and some inquiry into the associated bother or distress experienced by the patient. A simple question into the presence or absence of dyspnea would be unlikely to help guide therapy, as complete relief of dyspnea in advanced disease would not be anticipated. Additional knowledge gaps include standards for clinical dyspnea care, assessment in the cognitively impaired, and evaluation of effectiveness of dyspnea care for patients with advanced disease. C1 [Mularski, Richard A.] Oregon Hlth & Sci Univ, Ctr Hlth Res, Portland, OR 97227 USA. [Campbell, Margaret L.] Wayne State Univ, Detroit Receiving Hosp Ctr Hlth Res, Detroit, MI USA. [Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Reeve, Bryce B.; Clauser, Steve B.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Basch, Ethan] Mem Sloan Kettering Canc Ctr, Hlth Outcomes Grp, New York, NY 10021 USA. [Maxwell, Terri L.] ExcelleRx Inc, Philadelphia, PA USA. [Hoverman, J. Russell] Texas Oncol, Dallas, TX USA. [Cuny, Joanne] Univ HealthSyst Consortium, Oak Brook, IL USA. [Snyder, Claire; Dy, Sydney] Johns Hopkins Sch Publ Hlth, Dept Hlth Policy & Management, Johns Hopkins Sch Med, Div Gen Internal Med, Baltimore, MD USA. [Seow, Hsien] McMaster Univ, Dept Oncol, Hamilton, ON, Canada. RP Mularski, RA (reprint author), Oregon Hlth & Sci Univ, Ctr Hlth Res, 3800 N Interstate,WIN 1060, Portland, OR 97227 USA. EM Richard.A.Mularski@kpchr.org OI Campbell, Margaret/0000-0003-4517-690X FU Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services [290-2005-00341]; Spiration, Inc.; Novartis; Amgen; Wyeth Pharmaceuticals; United Healthcare FX Supported by Contract No. 290-2005-00341 from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. The Symposium on Developing a Framework to Assess Cancer Quality Indicators for End-of-Life Care was held in Baltimore, MD on April 28, 2008. The authors of this manuscript are responsible for its content. Statements in the manuscript should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.; R.A.M. received 850,001-$100,000 from Spiration, Inc., and 850,001-8100,001 from Novartis in industry-sponsored grants. M.L.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.M.A. received more than 8100,001 from Amgen in grants. B.B.R. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. E.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. T.L.M. is a full-time employee of excelleRx, Inc., and received S10,001-850,000 from Wyeth Pharmaceuticals in industry-sponsored grants for database analysis related to constipation prevalence at the end of life. J.R.H. received $1,001-85,000 from United Healthcare in advisory board fees. j.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.B.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. C.S. does not have a financial relationship with a commercial I. entity that has an interest in the subject of this manuscript. H.S. does not NR 50 TC 20 Z9 20 U1 1 U2 3 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 MAR 15 PY 2010 VL 181 IS 6 BP 534 EP 538 DI 10.1164/rccm.200903-0462PP PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 632RX UT WOS:000280446500005 PM 20056904 ER PT J AU Sarosy, GA Hussain, MM Seiden, MV Fuller, AF Nikrui, N Goodman, A Minasian, L Reed, E Steinberg, SM Kohn, EC AF Sarosy, Gisele A. Hussain, Mahrukh M. Seiden, Michael V. Fuller, Arlan F. Nikrui, Najmosama Goodman, Annekathryn Minasian, Lori Reed, Eddie Steinberg, Seth M. Kohn, Elise C. TI Ten-Year Follow-Up of a Phase 2 Study of Dose-Intense Paclitaxel With Cisplatin and Cyclophosphamide as Initial Therapy for Poor-Prognosis, Advanced-Stage Epithelial Ovarian Cancer SO CANCER LA English DT Article DE ovarian neoplasms; paclitaxel; cyclophosphamide; cisplatin; antineoplastic combined chemotherapy protocols; filgrastim; drug dose-response relation ID GYNECOLOGIC-ONCOLOGY-GROUP; CARCINOMA CELL-LINES; 1ST-LINE TREATMENT; IV; PACLITAXEL/CARBOPLATIN; CYTOTOXICITY AB BACKGROUND: The objective of this study was to assess activity and toxicity in patients with newly diagnosed, advanced-stage epithelial ovarian cancer (EOC) who were receiving dose-intense paclitaxel, cyclophosphamide, cisplatin, and filgrastim delivered with a flexible dosing schedule. METHODS: Patients with stage III/IV EOC received cyclophosphamide 750 mg/m(2), followed by a 24-hour infusion of paclitaxel 250 mg/m(2) and cisplatin 75 mg/m(2) on Day 2. Filgrastim began on Day 3 at 10 mu g/kg daily for 9 days. Patients received 6 cycles of all drugs. Those who achieved a pathologic complete response or had microscopic residual disease at the conclusion of 6 cycles of therapy received an additional 2 to 4 cycles of paclitaxel with cyclophosphamide. Patients who had an objective response continued on cyclophosphamide and paclitaxel. RESULTS: Sixty-two patients were enrolled. Thirty-two of 62 patients had stage IIIC disease, and 26 of 62 patients had stage IV disease. According to an intent-to-treat analysis, 55 patients (89%) experienced a clinical complete remission. At a median potential follow-up of 11.4 years, the median progression-free survival was 18.9 months, and the median survival was 5.4 years. The most serious toxicity was grade 3/4 neutropenic fever (35%). Although all participants developed peripheral neuropathy, improvement in neuropathic symptoms began with the decrease or cessation of paclitaxel. CONCLUSIONS: The studied regimen yielded a high response rate and encouraging overall survival. The current data and those reported by the Japanese Gynecologic Cincology Group suggest that further study is warranted of dose-dense or dose-intense paclitaxel regimens in women with newly diagnosed, advanced-stage EOC. Cancer 2010;116:1476-84. (C) 2070 American Cancer Society. C1 [Sarosy, Gisele A.; Hussain, Mahrukh M.; Minasian, Lori; Reed, Eddie; Kohn, Elise C.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Seiden, Michael V.] Massachusetts Gen Hosp, Div Canc Biol, Boston, MA 02114 USA. [Fuller, Arlan F.; Nikrui, Najmosama; Goodman, Annekathryn] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 10 Ctr Dr,MSC 1906, Bethesda, MD 20892 USA. EM kohne@mail.nih.gov FU National Institutes of Health; National Cancer Institute, Center for Cancer Research; Amgen Corporation FX Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Patient care Support was provided to the Massachusetts General Hospital investigators from Amgen Corporation. NR 24 TC 13 Z9 13 U1 0 U2 0 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 MAR 15 PY 2010 VL 116 IS 6 BP 1476 EP 1484 DI 10.1002/cncr.24861 PG 9 WC Oncology SC Oncology GA 564SY UT WOS:000275238800015 PM 20091841 ER PT J AU Richards, WG Godleski, JJ Yeap, BY Corson, JM Chirieac, LR Zellos, L Mujoomdar, A Jaklitsch, MT Bueno, R Sugarbaker, DJ AF Richards, William G. Godleski, John J. Yeap, Beow Y. Corson, Joseph M. Chirieac, Lucian R. Zellos, Lambros Mujoomdar, Aneil Jaklitsch, Michael T. Bueno, Raphael Sugarbaker, David J. TI Proposed Adjustments to Pathologic Staging of Epithelial Malignant Pleural Mesothelioma Based on Analysis of 354 Cases SO CANCER LA English DT Article DE diffuse malignant pleural mesothelioma; pathologic staging; extrapleural pneumonectomy; epithelial mesothelioma; TNM staging ID MULTIMODALITY THERAPY; PROGNOSTIC-FACTORS; EXPERIENCE; SYSTEM; RESECTION; SURVIVAL; DIFFUSE AB BACKGROUND: Several pathologic staging systems for malignant pleural mesothelioma (MPM) have been published, but none of them provide optimal survival stratification or stage distribution among patients treated with surgery. Interpretation of prior studies that correlate pathologic factors with outcome has been confounded by the inclusion of patients undergoing differing surgical procedures and with varied tumor histology. METHODS: We examined pathologic characteristics, previously included in published studies, and explored correlations with outcome among patients with epithelioid MPM who underwent extrapleural pneumonectomy (EPP) at Brigham and Women's Hospital (BWH). Comparisons of survival among patients with and without each tumor or lymph node feature guided adjustments to the American Joint Commission on Cancer (AJCC)/International Union Against Cancer (UICC) classification criteria. Proportional hazards modeling of TN combinations guided adjustments to stage groupings. RESULTS: Three hundred fifty-four patients were resectable by EPP and had complete pathologic data. Overall median survival was 18 months from surgery. By AJCC/UICC criteria, 233 (66%) patients were stage 111, whereas by BWH criteria, 194 (SS%) patients were stage III. T classification criteria were adjusted-based on prevalence and relation to survival. N status correlated significantly with survival. Regrouping of TN combinations based on relative hazard and Kaplan-Meier survival analysis resulted in improved stage distribution (stage I-IV: 8%, 43%, 33%, 16%, respectively) and survival stratification (SI, 26, 15, 8 months, respectively). CONCLUSIONS: Proposed adjustments to TNM staging criteria improved outcome stratification of patients with epithelial tumor histology who received surgical therapy by EPP and complete pathologic assessment. Determining relevance to other treatment or staging modalities will require verification in additional cohorts. Cancer 2010;116:1510-7. (C) 2070 American Cancer Society. C1 [Richards, William G.; Zellos, Lambros; Mujoomdar, Aneil; Jaklitsch, Michael T.; Bueno, Raphael; Sugarbaker, David J.] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. [Richards, William G.; Godleski, John J.; Yeap, Beow Y.; Corson, Joseph M.; Chirieac, Lucian R.; Zellos, Lambros; Mujoomdar, Aneil; Jaklitsch, Michael T.; Bueno, Raphael; Sugarbaker, David J.] Brigham & Womens Hosp, Int Mesothelioma Program, Boston, MA 02115 USA. [Godleski, John J.; Corson, Joseph M.; Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Richards, WG (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM wrichards@partners.org FU International Mesothelionia Program FX Supported by the International Mesothelionia Program. The authors made no further disclosures. NR 22 TC 30 Z9 31 U1 0 U2 0 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 MAR 15 PY 2010 VL 116 IS 6 BP 1510 EP 1517 DI 10.1002/cncr.24886 PG 8 WC Oncology SC Oncology GA 564SY UT WOS:000275238800019 PM 20108310 ER PT J AU Rothenberg, SM Mohapatra, G Rivera, MN Winokur, D Greninger, P Nitta, M Sadow, PM Sooriyakumar, G Brannigan, BW Ulman, MJ Perera, RM Wang, R Tam, A Ma, XJ Erlander, M Sgroi, DC Rocco, JW Lingen, MW Cohen, EEW Louis, DN Settleman, J Haber, DA AF Rothenberg, S. Michael Mohapatra, Gayatry Rivera, Miguel N. Winokur, Daniel Greninger, Patricia Nitta, Mai Sadow, Peter M. Sooriyakumar, Gaya Brannigan, Brian W. Ulman, Matthew J. Perera, Rushika M. Wang, Rui Tam, Angela Ma, Xiao-Jun Erlander, Mark Sgroi, Dennis C. Rocco, James W. Lingen, Mark W. Cohen, Ezra E. W. Louis, David N. Settleman, Jeffrey Haber, Daniel A. TI A Genome-Wide Screen for Microdeletions Reveals Disruption of Polarity Complex Genes in Diverse Human Cancers SO CANCER RESEARCH LA English DT Article ID REPRESENTATIONAL DIFFERENCE ANALYSIS; COPY-NUMBER; CELL POLARITY; ARRAY; HYBRIDIZATION; CARCINOMA; MICROARRAYS; EXPRESSION; DROSOPHILA; PATTERNS AB In a genome-wide screen of 684 cancer cell lines, we identified homozygous intragenic microdeletions involving genes encoding components of the apical-basal cell polarity complexes. Among these, PARD3 is disrupted in cell lines and primary tumors from squamous carcinomas and glioblastomas. Reconstituting PARD3 expression in both cell types restores tight junctions and retards contact-dependent proliferation. Searching specifically for small intragenic microdeletions using high-resolution genomic arrays may be complementary to other genomic deletion screens and resequencing efforts in identifying new tumor suppressor genes. Cancer Res; 70(6); 2158-64. (C) 2010 AACR. C1 [Rothenberg, S. Michael; Mohapatra, Gayatry; Rivera, Miguel N.; Winokur, Daniel; Greninger, Patricia; Nitta, Mai; Sooriyakumar, Gaya; Brannigan, Brian W.; Ulman, Matthew J.; Perera, Rushika M.; Tam, Angela; Sgroi, Dennis C.; Rocco, James W.; Louis, David N.; Settleman, Jeffrey; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Greninger, Patricia; Tam, Angela; Settleman, Jeffrey] Harvard Univ, Ctr Mol Therapeut, Sch Med, Charlestown, MA USA. [Rothenberg, S. Michael; Rivera, Miguel N.; Haber, Daniel A.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Rothenberg, S. Michael] Massachusetts Gen Hosp, Ctr Head & Neck Canc, Boston, MA 02114 USA. [Mohapatra, Gayatry; Rivera, Miguel N.; Nitta, Mai; Sadow, Peter M.; Sgroi, Dennis C.; Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wang, Rui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Ma, Xiao-Jun; Erlander, Mark] Biotheranostics, San Diego, CA USA. [Lingen, Mark W.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Cohen, Ezra E. W.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, CNY7 Bldg 149,13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu; haber@helix.mgh.harvard.edu FU Howard Hughes Medical Institute; NIH [RO1 CA207186, RO1 CA57683, K08 DK080175]; T32 Institutional Ruth L. Kirschstein National Research Service Award; MGH; Burroughs Wellcome Fund FX Grant Support; Howard Hughes Medical Institute (D. A. Haber, M.N. Rivera) and NIH grants RO1 CA207186 (D. A. Haber) and RO1 CA57683 (D.N. Louis). S. M. Rothenberg is supported by a T32 Institutional Ruth L. Kirschstein National Research Service Award and the MGH Tosteson Postdoctoral Fellowship. M.N. Rivera is supported by NIH grant K08 DK080175, MGH, and the Burroughs Wellcome Fund. NR 21 TC 41 Z9 41 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2010 VL 70 IS 6 BP 2158 EP 2164 DI 10.1158/0008-5472.CAN-09-3458 PG 7 WC Oncology SC Oncology GA 607GA UT WOS:000278485900003 PM 20215515 ER PT J AU Yang, XWH Flores, LM Li, QL Zhou, PC Xu, FH Krop, IE Hemler, ME AF Yang, Xiuwei H. Flores, Ludmila M. Li, Qinglin Zhou, Pengcheng Xu, Fenghui Krop, Ian E. Hemler, Martin E. TI Disruption of Laminin-Integrin-CD151-Focal Adhesion Kinase Axis Sensitizes Breast Cancer Cells to ErbB2 Antagonists SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; ALPHA-6-BETA-4 INTEGRIN; LUNG-CANCER; IN-VITRO; TRASTUZUMAB RESISTANCE; CLINICAL-SIGNIFICANCE; TETRASPANIN PROTEINS; LAPATINIB RESISTANCE; DRUG-RESISTANCE; CARCINOMA CELLS AB Resistance to anti-ErbB2 agents is a significant problem in the treatment of human ErbB2+ breast cancers. We show here that adhesion of human ErbB2+ breast cancer cells to basement membrane laminin-5 provides substantial resistance to trastuzumab and lapatinib, agents that respectively target the extracellular and kinase domains of ErbB2. Knockdown of laminin-binding integrins (alpha 6 beta 4, alpha 3 beta 1) or associated tetraspanin protein CD151 reversed laminin-5 resistance and sensitized ErbB2+ cells to trastuzumab and lapatinib. CD151 knockdown, together with trastuzumab treatment, inhibited ErbB2 activation and downstream signaling through Akt, Erk1/2, and focal adhesion kinase (FAK). Hence, ErbB2 function in mammary tumor cells is promoted by integrin-mediated adhesion to laminin-5, with strong support by CD151, leading to signaling through FAK. Consequently, removal or inhibition of any of these components (laminin-5, integrin, CD151, FAK) markedly sensitizes cells to anti-ErbB2 agents. These new insights should be useful when devising strategies for overcoming drug resistance in ErbB2+ cancers. Cancer Res; 70(6); 2256-63. (C) 2010 AACR. C1 [Yang, Xiuwei H.; Li, Qinglin; Xu, Fenghui; Hemler, Martin E.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Flores, Ludmila M.; Krop, Ian E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhou, Pengcheng] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Flores, Ludmila M.] Univ Massachusetts, Dept Biol, Boston, MA 02125 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Room D1430,44 Binney St, Boston, MA 02115 USA. EM Martin_Hemler@DFCI.Harvard.EDU RI Li, Qinglin/K-2570-2015 OI Li, Qinglin/0000-0002-4125-1944 FU NIH [CA42368]; S.G. Komen Career Catalyst Award; DOD [W81XWH-06-BCRP-CA]; Center for Clinical and Translational Research at Dana-Farber Cancer Institute FX Grant Support; NIH grant CA42368 (M. E. Hemler), S.G. Komen Career Catalyst Award, and DOD W81XWH-06-BCRP-CA Concept Award (X. H. Yang) and Center for Clinical and Translational Research at Dana-Farber Cancer Institute. NR 51 TC 61 Z9 63 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2010 VL 70 IS 6 BP 2256 EP 2263 DI 10.1158/0008-5472.CAN-09-4032 PG 8 WC Oncology SC Oncology GA 607GA UT WOS:000278485900013 PM 20197472 ER PT J AU Zhang, X Gejman, R Mahta, A Zhong, Y Rice, KA Zhou, YL Cheunsuchon, P Louis, DN Klibanski, A AF Zhang, Xun Gejman, Roger Mahta, Ali Zhong, Ying Rice, Kimberley A. Zhou, Yunli Cheunsuchon, Pornsuk Louis, David N. Klibanski, Anne TI Maternally Expressed Gene 3, an Imprinted Noncoding RNA Gene, Is Associated with Meningioma Pathogenesis and Progression SO CANCER RESEARCH LA English DT Article ID MOUSE-CHROMOSOME 12; PITUITARY-ADENOMAS; EXPRESSION; TUMOR; MEG3; GTL2; P53; MUTATION; GROWTH; REGION AB Meningiomas are common tumors, representing 15% to 25% of all central nervous system tumors. NF2 gene inactivation on chromosome 22 has been shown as an early event in tumorigenesis; however, few factors underlying tumor growth and progression have been identified. The chromosomal abnormalities of 14q32 are often associated with meningioma pathogenesis and progression; therefore, it has been proposed that an as yet unidentified tumor suppressor is present at this locus. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 which encodes a noncoding RNA with an antiproliferative function. We found that MEG3 mRNA is highly expressed in normal arachnoidal cells. However, MEG3 is not expressed in the majority of human meningiomas or the human meningioma cell lines IOMM-Lee and CH157-MN. There is a strong association between loss of MEG3 expression and tumor grade. Allelic loss at the MEG3 locus is also observed in meningiomas, with increasing prevalence in higher grade tumors. In addition, there is an increase in CpG methylation within the promoter and the imprinting control region of MEG3 gene in meningiomas. Functionally, MEG3 suppresses DNA synthesis in both IOMM-Lee and CH157-MN cells by similar to 60% in bromodeoxyuridine incorporation assays. Colony-forming efficiency assays show that MEG3 inhibits colony formation in CH157-MN cells by similar to 80%. Furthermore, MEG3 stimulates p53-mediated transactivation in these cell lines. Therefore, these data are consistent with the hypothesis that MEG3, which encodes a noncoding RNA, may be a tumor suppressor gene at chromosome 14q32 involved in meningioma progression via a novel mechanism. Cancer Res; 70(6); 2350-8. (C) 2010 AACR. C1 [Zhang, Xun; Gejman, Roger; Mahta, Ali; Zhong, Ying; Rice, Kimberley A.; Zhou, Yunli; Cheunsuchon, Pornsuk; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Gejman, Roger; Cheunsuchon, Pornsuk; Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL457,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org RI Cheunsuchon, Pornsuk/O-7915-2015 OI Cheunsuchon, Pornsuk/0000-0001-8851-3553 FU NIH [R01-DK-40947]; Guthart Family Foundation FX Grant Support; NIH R01-DK-40947 (A. Klibanski) and The Guthart Family Foundation. NR 50 TC 131 Z9 147 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2010 VL 70 IS 6 BP 2350 EP 2358 DI 10.1158/0008-5472.CAN-09-3885 PG 9 WC Oncology SC Oncology GA 607GA UT WOS:000278485900022 PM 20179190 ER PT J AU Schoeberl, B Faber, AC Li, DN Liang, MC Crosby, K Onsum, M Burenkova, O Pace, E Walton, Z Nie, L Fulgham, A Song, Y Nielsen, UB Engelman, JA Wong, KK AF Schoeberl, Birgit Faber, Anthony C. Li, Danan Liang, Mei-Chih Crosby, Katherine Onsum, Matthew Burenkova, Olga Pace, Emily Walton, Zandra Nie, Lin Fulgham, Aaron Song, Youngchul Nielsen, Ulrik B. Engelman, Jeffrey A. Wong, Kwok-Kin TI An ErbB3 Antibody, MM-121, Is Active in Cancers with Ligand-Dependent Activation SO CANCER RESEARCH LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; BREAST-CANCER; PHOSPHATIDYLINOSITOL 3-KINASE; ANTITUMOR ACTION; FACTOR RECEPTOR; IN-VIVO; EGFR; KINASE; HER3 AB ErbB3 is a critical activator of phosphoinositide 3-kinase (PI3K) signaling in epidermal growth factor receptor (EGFR; ErbB1), ErbB2 [human epidermal growth factor receptor 2 (HER2)], and [hepatocyte growth factor receptor (MET)] addicted cancers, and reactivation of ErbB3 is a prominent method for cancers to become resistant to ErbB inhibitors. In this study, we evaluated the in vivo efficacy of a therapeutic anti-ErbB3 antibody, MM-121. We found that MM-121 effectively blocked ligand-dependent activation of ErbB3 induced by either EGFR, HER2, or MET. Assessment of several cancer cell lines revealed that MM-121 reduced basal ErbB3 phosphorylation most effectively in cancers possessing ligand-dependent activation of ErbB3. In those cancers, MM-121 treatment led to decreased ErbB3 phosphorylation and, in some instances, decreased ErbB3 expression. The efficacy of single-agent MM-121 was also examined in xenograft models. A machine learning algorithm found that MM-121 was most effective against xenografts with evidence of ligand-dependent activation of ErbB3. We subsequently investigated whether MM-121 treatment could abrogate resistance to anti-EGFR therapies by preventing reactivation of ErbB3. We observed that an EGFR mutant lung cancer cell line (HCC827), made resistant to gefitinib by exogenous heregulin, was resensitized by MM-121. In addition, we found that a de novo lung cancer mouse model induced by EGFR T790M-L858R rapidly became resistant to cetuximab. Resistance was associated with an increase in heregulin expression and ErbB3 activation. However, concomitant cetuximab treatment with MM-121 blocked reactivation of ErbB3 and resulted in a sustained and durable response. Thus, these results suggest that targeting ErbB3 with MM-121 can be an effective therapeutic strategy for cancers with ligand-dependent activation of ErbB3. Cancer Res; 70(6); 2485-94. (C)2010 AACR. C1 [Faber, Anthony C.; Song, Youngchul; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Schoeberl, Birgit; Onsum, Matthew; Burenkova, Olga; Pace, Emily; Nie, Lin; Fulgham, Aaron; Nielsen, Ulrik B.] Merrimack Pharmaceut Inc, Cambridge, MA USA. [Li, Danan; Liang, Mei-Chih; Walton, Zandra; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Li, Danan; Liang, Mei-Chih; Walton, Zandra; Wong, Kwok-Kin] Harvard Canc Ctr, Ludwig Ctr Dana Farber, Boston, MA USA. [Engelman, Jeffrey A.; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Crosby, Katherine] Cell Signaling Technol, Danvers, MA USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM jengelman@partners.org; kwong1@partners.org OI wong, kwok kin/0000-0001-6323-235X FU Dana-Farber-Harvard Cancer Center Lung Cancer [P50 CA090578]; NIH [K08 AG024004, R01 AG2400401, R01 CA122794, R01 CA140594, K08 CA120060, R01CA137008, R01CA140594]; DF/HCC Gastrointestinal Cancer SPORE [P50 CA127003]; American Association for Cancer Research; American Cancer Society [RSG-06102- 01-CCE]; Ellison Foundation FX Grant Support; Dana-Farber-Harvard Cancer Center Lung Cancer Specialized Program of Research Excellence (SPORE) grant P50 CA090578 (J.A. Engelman and K-K. Wong); NIH grants K08 AG024004 (K-K. Wong), R01 AG2400401 (K-K. Wong), R01 CA122794 (K-K. Wong), R01 CA140594 (J.A. Engelman and K-K. Wong), K08 grant CA120060 (J.A. Engelman), R01CA137008 (J.A. Engelman), and R01CA140594 (J.A. Engelman); DF/HCC Gastrointestinal Cancer SPORE P50 CA127003 (J.A. Engelman); American Association for Cancer Research (J.A. Engelman); V Foundation (J.A. Engelman); American Cancer Society RSG-06102- 01-CCE (J.A. Engelman); and Ellison Foundation Scholar (J.A. Engelman). NR 25 TC 151 Z9 155 U1 2 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2010 VL 70 IS 6 BP 2485 EP 2494 DI 10.1158/0008-5472.CAN-09-3145 PG 10 WC Oncology SC Oncology GA 607GA UT WOS:000278485900036 PM 20215504 ER PT J AU Chan, SY Loscalzo, J AF Chan, Stephen Y. Loscalzo, Joseph TI MicroRNA-210 A unique and pleiotropic hypoxamir SO CELL CYCLE LA English DT Review DE microRNA; hypoxia; miR-210; hypoxia inducible factor; metabolism; proliferation; angiogenesis; apoptosis; cell cycle; Pasteur effect ID SULFUR CLUSTER BIOGENESIS; RECEPTOR TYROSINE KINASE; REPAIR GENE-EXPRESSION; NITRIC-OXIDE; MICROPROCESSOR COMPLEX; ESCHERICHIA-COLI; MESSENGER-RNAS; CELL-CARCINOMA; BREAST-CANCER; HUMAN-DISEASE AB Inadequate oxygen availability or hypoxia induces a complex and still incompletely understood set of adaptations that influence cellular survival and function. Many of these adaptations are directly controlled by a master transcription factor, hypoxia inducible factor-alpha (HIF-alpha). In response to hypoxia, HIF-alpha levels increase and directly induce the transcription of > 100 genes, influencing functions ranging from metabolism, survival, proliferation, migration, to angiogenesis, among others. Recently, it has been demonstrated that a specific set of microRNA molecules are upregulated by hypoxia, which we denote here as "hypoxamirs." In particular, the HIF-responsive hypoxamir microRNA-210 (miR-210) is a unique microRNA that is evolutionarily conserved and ubiquitously expressed in hypoxic cell and tissue types. A number of direct targets of miR-210 have been identified by in silico, transcriptional and biochemical methods, a subset of which have been extensively validated. As a result, miR-210 has been mechanistically linked to the control of a wide range of cellular responses known to influence normal developmental physiology as well as a number of hypoxia-dependent disease states, including tissue ischemia, inflammation and tumorigenesis. Thus, reflecting the pleiotropic actions of HIF-alpha, miR-210 appears to function as a "master microRNA" relevant for the control of diverse functions in the hypoxic state. C1 [Loscalzo, Joseph] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Chan, Stephen Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. RP Loscalzo, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. EM jloscalzo@partners.org FU AHA [0825906D]; NIH [HL 61795, NO1 HV 28178, PO1 81587, U54 HL 70819] FX This work was supported by AHA grant 0825906D (S.Y.C.), and NIH grants HL 61795, NO1 HV 28178, PO1 81587, U54 HL 70819 (J.L.). No conflicts of interest are reported. We apologize to those authors whose work is not cited due to space restrictions. We thank the Loscalzo laboratory for fruitful discussions; T. Lis for graphic design; S. K. Chan and J.W. Snow for critical reading of the manuscript; and S. Tribuna for expert administrative assistance. NR 99 TC 125 Z9 134 U1 2 U2 13 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 15 PY 2010 VL 9 IS 6 BP 1072 EP 1083 PG 12 WC Cell Biology SC Cell Biology GA 569XT UT WOS:000275636900013 PM 20237418 ER PT J AU Gomez-Baldo, L Schmidt, S Maxwell, CA Bonifaci, N Gabaldon, T Vidalain, PO Senapedis, W Kletke, A Rosing, M Barnekow, A Rottapel, R Capella, G Vidal, M Astrinidis, A Piekorz, RP Pujana, MA AF Gomez-Baldo, Laia Schmidt, Stephan Maxwell, Christopher A. Bonifaci, Nuria Gabaldon, Toni Vidalain, Pierre-Olivier Senapedis, William Kletke, Anja Rosing, Mechthild Barnekow, Angelika Rottapel, Robert Capella, Gabriel Vidal, Marc Astrinidis, Aristotelis Piekorz, Roland P. Angel Pujana, Miguel TI TACC3-TSC2 maintains nuclear envelope structure and controls cell division SO CELL CYCLE LA English DT Article DE TSC; TACC3; centrosome; nuclear envelope; mitosis ID TUBEROUS SCLEROSIS COMPLEX; TUMOR-SUPPRESSOR; GENE-PRODUCT; ACTIN CYTOSKELETON; PRIMARY CILIUM; C-ELEGANS; EXPRESSION PROFILES; INTERACTOME NETWORK; MUTATIONAL ANALYSIS; BINDING PARTNER AB Studies of the role of tuberous sclerosis complex (TSC) proteins (TSC1/TSC2) in pathology have focused mainly on their capacity to regulate translation and cell growth, but their relationship with alterations of cellular structures and the cell cycle is not yet fully understood. The transforming acidic coiled-coil (TACC) domain-containing proteins are central players in structures and processes connected to the centrosome. Here, TACC3 interactome mapping identified TSC2 and 15 other physical interactors, including the evolutionary conserved interactions with ch-TOG/CKAP5 and FAM161B. TACC3 and TSC2 co-localize and co-purify with components of the nuclear envelope, and their deficiency causes morphological alterations of this structure. During cell division, TACC3 is necessary for the proper localization of phospho-Ser939 TSC2 at spindle poles and cytokinetic bridges. Accordingly, abscission alterations and increased frequency of binucleated cells were observed in Tacc3- and Tsc2-deficient cells relative to controls. In regulating cell division, TSC2 acts epistatically to TACC3 and, in addition to canonical TSC/mTOR signaling and cytokinetic associations, converges to the early mitotic checkpoint mediated by CHFR, consistently with nuclear envelope associations. Our findings link TACC3 to novel structural and cell division functions of TSC2, which may provide additional explanations for the clinical and pathological manifestations of lymphangioleiomyomatosis (LAM) disease and TSC syndrome, including the greater clinical severity of TSC2 mutations compared to TSC1 mutations. C1 [Gomez-Baldo, Laia; Maxwell, Christopher A.; Capella, Gabriel; Angel Pujana, Miguel] Bellvitge Inst Biomed Res, Catalan Inst Oncol, Translat Res Lab, Barcelona, Spain. [Bonifaci, Nuria; Angel Pujana, Miguel] Bellvitge Inst Biomed Res, Catalan Inst Oncol, Bioinformat & Biostat Unit, Barcelona, Spain. [Schmidt, Stephan; Kletke, Anja; Piekorz, Roland P.] Univ Dusseldorf, Dept Biochem & Mol Biol 2, Dusseldorf, Germany. [Gabaldon, Toni] Ctr Genom Regulat, Bioinformat & Genom Program, Barcelona, Spain. [Vidalain, Pierre-Olivier] Inst Pasteur, Ctr Natl Rech Sci, Lab Genom Viral & Vaccinat, Paris, France. [Senapedis, William; Astrinidis, Aristotelis] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Rosing, Mechthild; Barnekow, Angelika] Univ Munster, Dept Expt Tumorbiol, Munster, Germany. [Rottapel, Robert] Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. [Vidal, Marc] Harvard Univ, Sch Med, CCSB, Boston, MA USA. [Vidal, Marc] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Astrinidis, Aristotelis] Drexel Univ, Dept Biochem & Mol Biol, Coll Med, Philadelphia, PA 19104 USA. RP Pujana, MA (reprint author), Bellvitge Inst Biomed Res, Catalan Inst Oncol, Translat Res Lab, Barcelona, Spain. EM aristotelis.astreinidis@drexelmed.edu; roland.piekorz@uniduesseldorf.de; mapujana@ico.scs.es RI Gabaldon, Toni/A-7336-2008; Astrinidis, Aristotelis/A-1396-2010; Maxwell, Christopher/B-3044-2011; pujana, Miguel Angel/N-3127-2014 OI Gabaldon, Toni/0000-0003-0019-1735; Maxwell, Christopher/0000-0002-0860-4031; pujana, Miguel Angel/0000-0003-3222-4044 NR 101 TC 24 Z9 25 U1 0 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 15 PY 2010 VL 9 IS 6 BP 1143 EP 1155 PG 13 WC Cell Biology SC Cell Biology GA 569XT UT WOS:000275636900021 PM 20237422 ER PT J AU El Jamali, A Valente, AJ Clark, RA AF El Jamali, Amina Valente, Anthony J. Clark, Robert A. TI Regulation of phagocyte NADPH oxidase by hydrogen peroxide through a Ca2+/c-Abl signaling pathway SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE NADPH oxidase; NOX2; Neutrophil; Superoxide; Hydrogen peroxide; Signaling; c-Abl, Calcium; Free radicals ID ABL TYROSINE KINASE; NEUTROPHIL RESPIRATORY BURST; SMOOTH-MUSCLE-CELLS; C-DELTA; OXIDATIVE STRESS; GROWTH-FACTOR; HEMATOPOIETIC-CELLS; CALCIUM IONOPHORE; HUMAN MONOCYTES; MYC EXPRESSION AB The importance of H2O2 as a cellular signaling molecule has been demonstrated in a number of cell types and pathways. Here we explore a positive feedback mechanism of H2O2-mediated regulation of the phagocyte respiratory burst NADPH oxidase (NOX2). H2O2 induced a dose-dependent stimulation of superoxide production in human neutrophils, as well as in K562 leukemia cells overexpressing NOX2 system components. Stimulation was abrogated by the addition of catalase, the extracellular Ca2+ chelator BAPTA, the T-type Ca2+ channel inhibitor mibefradil, the PKC delta inhibitor rottlerin, or the c-Abl nonreceptor tyrosine kinase inhibitor imatinib mesylate or by overexpression of a dominant-negative form of c-Abl. H2O2 induced phosphorylation of tyrosine 311 on PKC delta and this activating phosphorylation was blocked by treatment with rottlerin, imatinib mesylate, or BAPTA. Rac GTPase activation in response to H2O2 was abrogated by BAPTA, imatinib mesylate, or rottlerin. In conclusion, H2O2 stimulates NOX2-mediated superoxide generation in neutrophils and K562/NOX2 cells via a signaling pathway involving Ca2+ influx and c-Abl tyrosine kinase acting upstream of PKC delta. This positive feedback regulatory pathway has important implications for amplifying the innate immune response and contributing to oxidative stress in inflammatory disorders. (c) 2009 Elsevier Inc. All rights reserved. C1 [El Jamali, Amina] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. RP El Jamali, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM AkoulouzeBik@uthscsa.edu FU National Institutes of Health [R01-Al020866, T32 HL07446, P30-CA054174, P30-AG013319, P01-AG019316]; Department of Veterans Affairs FX This work was supported by grants from the National Institutes of Health (R01-Al020866 and T32 HL07446) and the Department of Veterans Affairs. The confocal microscopy studies were performed in the University of Texas Health Science Center Institutional Optical Imaging Facility, which is supported by NIH Grants P30-CA054174 (Cancer Therapy and Research Center), P30-AG013319 (Nathan Shock Center), and P01-AG019316 (Aging, Oxidative Stress and Cell Death). The authors thank Alain Virion and Yves Gorin for helpful discussion and critical review of the manuscript, Victoria Frohlich for expert guidance on the confocal microscope image acquisition and analysis, John Cornell for insightful advice on statistical analysis, and Maria Gamez and Doran Pearson for expert technical assistance. Dr. Clark is a scientific cofounder member of the Scientific Advisory Board and equity holder in GenKyoTex SA, a Swiss biotechnology start-up company with a primary goal of developing clinically useful inhibitors of the NOX family of NADPH oxidases. No other competing financial interests exist. NR 62 TC 19 Z9 19 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 15 PY 2010 VL 48 IS 6 BP 798 EP 810 DI 10.1016/j.freeradbiomed.2009.12.018 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 561WS UT WOS:000275011400006 PM 20043988 ER PT J AU Charest-Marcotte, A Dufour, CR Wilson, BJ Tremblay, AM Eichner, LJ Arlow, DH Mootha, VK Giguere, V AF Charest-Marcotte, Alexis Dufour, Catherine R. Wilson, Brian J. Tremblay, Annie M. Eichner, Lillian J. Arlow, Daniel H. Mootha, Vamsi K. Giguere, Vincent TI The homeobox protein Prox1 is a negative modulator of ERR alpha/PGC-1 alpha bioenergetic functions SO GENES & DEVELOPMENT LA English DT Article DE ChIP-on-chip; homeobox; mitochondrial respiration; nuclear receptor; regulon ID ERR-ALPHA; ENERGY HOMEOSTASIS; LIVER DEVELOPMENT; RECEPTOR-ALPHA; REQUIRES PROX1; COUP-TFII; GAMMA; GENE; TRANSCRIPTION; EXPRESSION AB Estrogen-related receptor alpha (ERR alpha) and proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) play central roles in the transcriptional control of energy homeostasis, but little is known about factors regulating their activity. Here we identified the homeobox protein prospero-related homeobox 1 (Prox1) as one such factor. Prox1 interacts with ERRa and PGC-1 alpha, occupies promoters of metabolic genes on a genome-wide scale, and inhibits the activity of the ERR alpha/PGC-1 alpha complex. DNA motif analysis suggests that Prox1 interacts with the genome through tethering to ERR alpha and other factors. Importantly, ablation of Prox1 and ERR alpha have opposite effects on the respiratory capacity of liver cells, revealing an unexpected role for Prox1 in the control of energy homeostasis. C1 [Charest-Marcotte, Alexis; Dufour, Catherine R.; Wilson, Brian J.; Tremblay, Annie M.; Eichner, Lillian J.; Giguere, Vincent] McGill Univ, Goodman Canc Ctr, Montreal, PQ H3A 1A3, Canada. [Charest-Marcotte, Alexis; Tremblay, Annie M.; Eichner, Lillian J.; Giguere, Vincent] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. [Arlow, Daniel H.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Syst Biol, Cambridge, MA 02142 USA. [Arlow, Daniel H.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Cambridge, MA 02142 USA. [Arlow, Daniel H.; Mootha, Vamsi K.] MIT Harvard, Broad Inst, Cambridge, MA 02142 USA. [Giguere, Vincent] McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada. [Giguere, Vincent] McGill Univ, Dept Oncol, Montreal, PQ H3G 1Y6, Canada. RP Giguere, V (reprint author), McGill Univ, Goodman Canc Ctr, Montreal, PQ H3A 1A3, Canada. EM vincent.giguere@mcgill.ca FU Canadian Institutes for Health Research [MOP-84227, MOP-77763]; American Diabetes Association/Smith Family Foundation FX We thank Carlo Ouellet for skillful technical assistance and Dr. Julie St- Pierre for careful reading of the manuscript. This work was supported by grants from the Canadian Institutes for Health Research (MOP-84227 and MOP-77763) and the American Diabetes Association/Smith Family Foundation. NR 25 TC 57 Z9 58 U1 2 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 2010 VL 24 IS 6 BP 537 EP 542 DI 10.1101/gad.1871610 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 569LU UT WOS:000275599400003 PM 20194433 ER PT J AU Kirsch, DG Grimm, J Guimaraes, AR Wojtkiewicz, GR Perez, BA Santiago, PM Anthony, NK Forbes, T Doppke, K Weissleder, R Jacks, T AF Kirsch, David G. Grimm, Jan Guimaraes, Alexander R. Wojtkiewicz, Gregory R. Perez, Bradford A. Santiago, Philip M. Anthony, Nikolas K. Forbes, Thomas Doppke, Karen Weissleder, Ralph Jacks, Tyler TI IMAGING PRIMARY LUNG CANCERS IN MICE TO STUDY RADIATION BIOLOGY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Genetically engineered mouse models of cancer; Lung cancer; Micro computed tomography; K-Ras; p53 ID RADIOTHERAPY; EXPRESSION AB Purpose: To image a genetically engineered mouse model of non small-cell lung cancer with micro computed tomography (micro-CT) to measure tumor response to radiation therapy. Methods and Materials: The Cre-loxP system was used to generate primary lung cancers in mice with mutation in K-ras alone or in combination with p53 mutation. Mice were serially imaged by micro-CT, and tumor volumes were determined. A comparison of tumor volume by micro-CT and tumor histology was performed. Tumor response to radiation therapy (15.5 Gy) was assessed with micro-CT. Results: The tumor volume measured with free-breathing micro-CT scans was greater than the volume calculated by histology. Nevertheless, this imaging approach demonstrated that lung cancers with mutant p53 grew more rapidly than lung tumors with wild-type p53 and also showed that radiation therapy increased the doubling time of p53 mutant lung cancers fivefold. Conclusions: Micro-CT is an effective tool to noninvasively measure the growth of primary lung cancers in genetically engineered mice and assess tumor response to radiation therapy. This imaging approach will be useful to study the radiation biology of lung cancer. (C) 2010 Elsevier Inc. C1 [Kirsch, David G.; Perez, Bradford A.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27708 USA. [Kirsch, David G.; Perez, Bradford A.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27708 USA. [Kirsch, David G.; Santiago, Philip M.; Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Kirsch, David G.; Anthony, Nikolas K.; Forbes, Thomas; Doppke, Karen] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Grimm, Jan; Guimaraes, Alexander R.; Wojtkiewicz, Gregory R.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Grimm, Jan; Guimaraes, Alexander R.; Wojtkiewicz, Gregory R.] Harvard Univ, Sch Med, Charlestown, MA USA. [Grimm, Jan] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Guimaraes, Alexander R.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Guimaraes, Alexander R.; Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA USA. [Guimaraes, Alexander R.; Weissleder, Ralph] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Jacks, Tyler] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Kirsch, DG (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Box 91006, Durham, NC 27708 USA. EM david.kirsch@duke.edu RI Grimm, Jan/B-1937-2008 FU Howard Hughes Medical Institute; American Cancer Society Institutional Research [K08 CA 114176, P50 CA86355, R24 CA92782, U24 CA 092782]; NCI [5-U01-CA84306, P30-CA14051]; RSNA FX Supported by the Howard Hughes Medical Institute (Ti., B.A.P.), American Cancer Society Institutional Research Grant, K08 CA 114176 (D.G.K.), P50 CA86355 (D.G.K., R.W.), R24 CA92782 (R.W.), U24 CA 092782 (R.W., Ti.), NCI grant 5-U01-CA84306 (T.J.), partially by Cancer Center Support (core) grant P30-CA14051 from the NCI (Ti.) and by a medical student seed grant from the RSNA (B.A.P.). Dr. Jacks is the David H. Koch Professor of Biology and a Daniel K. Ludwig Scholar. NR 14 TC 28 Z9 28 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2010 VL 76 IS 4 BP 973 EP 977 DI 10.1016/j.ijrobp.2009.11.038 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 573OO UT WOS:000275923900002 PM 20206017 ER PT J AU Mutyala, S Stewart, A Khan, AJ Cormack, RA O'Farrell, D Sugarbaker, D Devlin, PM AF Mutyala, Subhakar Stewart, Alexandra Khan, Atif J. Cormack, Robert A. O'Farrell, Desmond Sugarbaker, David Devlin, Phillip M. TI PERMANENT IODINE-125 INTERSTITIAL PLANAR SEED BRACHYTHERAPY FOR CLOSE OR POSITIVE MARGINS FOR THORACIC MALIGNANCIES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Thoracic tumors; Mediastinal tumors; Thoracic surgery; Brachytherapy seed implant; Lung brachytherapy ID LUNG; CANCER; CARCINOMA; TUMORS; TRIAL; JAPAN AB Purpose: To assess toxicity and outcome following permanent iodine-125 seed implant as an adjunct to surgical resection in cases of advanced thoracic malignancy. Methods and Materials: An institutional review board-approved retrospective review was performed. Fifty-nine patients were identified as having undergone thoracic brachytherapy seed implantation between September 1999 and December 2006. Data for patient demographics, tumor details, and morbidity and mortality were recorded. Results: Fifty-nine patients received 64 implants. At a median follow-up of 17 months, 1-year and 2-year Kaplan-Meier rates of estimated overall survival were 94.1% and 82.0%, respectively. The 1-year and 2-year local control rates were 80.1% and 67.4%, respectively. The median time to develop local recurrence was 11 months. Grades 3 and 4 toxicity rates were 12% at 1 year. Conclusions: This review shows relatively low toxicity for interstitial planar seed implantation after thoracic surgical resection. The high local control results suggest that an incomplete oncologic surgery plus a brachytherapy implant for treating advanced thoracic malignancy merit further investigation. (C) 2010 Elsevier Inc. C1 [Mutyala, Subhakar] Montefiore Med Ctr, Dept Radiat Oncol, New York, NY USA. [Mutyala, Subhakar] Albert Einstein Coll Med Bronx, New York, NY USA. [Stewart, Alexandra] Royal Surrey Cty Hosp, St Lukes Canc Ctr, Guildford, Surrey, England. [Khan, Atif J.] Canc Inst New Jersey, Dept Radiat Oncol, New Brunswick, NJ USA. [Cormack, Robert A.; O'Farrell, Desmond; Devlin, Phillip M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. [Sugarbaker, David] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Thorac Surg, Boston, MA 02115 USA. RP Mutyala, S (reprint author), Montefiore Med Ctr, Dept Radiat Oncol, 1625 Poplar St, Bronx, NY 10461 USA. EM smutyala@montefiore.org OI Cormack, Robert/0000-0001-5553-9984; Khan, Atif/0000-0001-8640-8530 NR 15 TC 18 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2010 VL 76 IS 4 BP 1114 EP 1120 DI 10.1016/j.ijrobp.2009.02.067 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 573OO UT WOS:000275923900022 PM 19540065 ER PT J AU Nanda, A Chen, MH D'Amico, AV AF Nanda, Akash Chen, Ming-Hui D'Amico, Anthony V. TI RESPONSE TO "PREDICTORS OF PROSTATE CANCER-SPECIFIC MORTALITY IN ELDERLY MEN WITH INTERMEDIATE-RISK PROSTATE CANCER TREATED WITH BRACHYTHERAPY WITH OR WITHOUT EXTERNAL BEAM RADIATION THERAPY" (INT J RADIAT ONCOL BIOL PHYS 2009, IN PRESS) IN REPLY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter C1 [Nanda, Akash] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nanda, A (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02115 USA. NR 1 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2010 VL 76 IS 4 BP 1275 EP 1275 DI 10.1016/j.ijrobp.2009.11.051 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 573OO UT WOS:000275923900045 ER PT J AU Zolopa, AR Berger, DS Lampiris, H Zhong, LJ Chuck, SL Enejosa, JV Kearney, BP Cheng, AK AF Zolopa, Andrew R. Berger, Daniel S. Lampiris, Harry Zhong, Lijie Chuck, Steven L. Enejosa, Jeffrey V. Kearney, Brian P. Cheng, Andrew K. TI Activity of Elvitegravir, a Once-Daily Integrase Inhibitor, against Resistant HIV Type 1: Results of a Phase 2, Randomized, Controlled, Dose-Ranging Clinical Trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; EXPERIENCED HIV-1-INFECTED PATIENTS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; TMC125 ETRAVIRINE; RALTEGRAVIR; INFECTION; EFFICACY; SAFETY; RITONAVIR AB Background. This phase 2, randomized, active-controlled, 48-week study assessed the noninferiority of the human immunodeficiency virus (HIV) integrase inhibitor elvitegravir to comparator ritonavir-boosted protease inhibitor (CPI/r) in treatment-experienced subjects. Methods. Subjects had HIV RNA levels >= 1000 copies/mL and >= 1 protease resistance mutation. Subjects received nucleoside or nucleotide reverse-transcriptase inhibitors (NRTIs) with or without T-20 and either CPI/r or once- daily elvitegravir at a dose of 20 mg, 50 mg, or 125 mg (blinded to dose) with ritonavir. After week 8, the independent data monitoring committee stopped the elvitegravir 20 mg arm and allowed subjects in the elvitegravir 50 mg and 125 mg arms to add protease inhibitors. The primary end point was the time-weighted average change from baseline in HIV RNA level through week 24 (DAVG(24)). Results. A total of 278 subjects with a median of 11 protease and 3 thymidine analog mutations were randomized and treated. One-half of subjects received NRTIs without expected antiviral activity. Compared with the DAVG(24) for the CPI/r arm (-1.19 log(10) copies/mL), the elvitegravir 50 mg arm was noninferior (-1.44 log(10) copies/mL), and the elvitegravir 125 mg arm was superior (-1.66 log(10) copies/mL; P = . 021). Efficacy was impacted by activity of background agents. There was no relationship between elvitegravir dosage and adverse events. Conclusions. Elvitegravir was well-tolerated and produced rapid virologic suppression that was durable with active background therapy. C1 [Zolopa, Andrew R.] Stanford Univ, Div Infect Dis & Geog Med, Stanford, CA 94305 USA. [Lampiris, Harry] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lampiris, Harry] San Francisco VA Med Ctr, San Francisco, CA USA. [Zhong, Lijie; Chuck, Steven L.; Enejosa, Jeffrey V.; Kearney, Brian P.; Cheng, Andrew K.] Gilead Sci Inc, Foster City, CA 94404 USA. [Berger, Daniel S.] Northstar Med Ctr, Chicago, IL USA. RP Zolopa, AR (reprint author), Stanford Univ, Div Infect Dis & Geog Med, 300 Pasteur Dr,Rm S-156,Grant Bldg, Stanford, CA 94305 USA. EM azolopa@stanford.edu FU Gilead Sciences FX Potential conflicts of interest: A.Z. has received grant support from Gilead Sciences and is on the National Advisory Board for Gilead Sciences; D.B. has received compensation for conducting clinical trials sponsored by Gilead Sciences and is a stockholder; H.L. has received grant support from Gilead Sciences; L.Z., S.C., J.E., B.K., and A.C. are employees and stockholders of Gilead Sciences.; Financial support: Gilead Sciences. NR 14 TC 80 Z9 81 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 15 PY 2010 VL 201 IS 6 BP 814 EP 822 DI 10.1086/650698 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 557JH UT WOS:000274664900004 PM 20146631 ER PT J AU Kovacs, A Karim, R Mack, WJ Xu, JA Chen, Z Operskalski, E Frederick, T Landay, A Voris, J Spencer, L Young, MA Tien, PC Augenbraun, M Strickler, HD Al-Harthi, L AF Kovacs, Andrea Karim, Roksana Mack, Wendy J. Xu, Jiaao Chen, Zhi Operskalski, Eva Frederick, Toni Landay, Alan Voris, John Spencer, La Shonda Young, Mary A. Tien, Phyllis C. Augenbraun, Michael Strickler, Howard D. Al-Harthi, Lena TI Activation of CD8 T Cells Predicts Progression of HIV Infection in Women Coinfected with Hepatitis C Virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CENTRAL-NERVOUS-SYSTEM; IMMUNE ACTIVATION; DISEASE PROGRESSION; MICROBIAL TRANSLOCATION; LYMPHOCYTE-ACTIVATION; CLINICAL PROGRESSION; BACTERIAL PNEUMONIA; VIRAL LOAD AB Background. Because activation of T cells is associated with human immunodeficiency virus (HIV) pathogenesis, CD4 and CD8 activation levels in patients coinfected with HIV and hepatitis C virus (HCV) may explain conflicting reports regarding effects of HCV on HIV disease progression. Methods. Kaplan-Meier and multivariate Cox regression models were used to study the risk of incident clinical AIDS and AIDS-related deaths among 813 HCV-negative women with HIV infection, 87 HCV-positive nonviremic women with HIV coinfection, and 407 HCV-positive viremic women with HIV coinfection (median follow-up time, 5.2 years). For 592 women, the percentages of activated CD4 and CD8 T cells expressing HLA-DR (DR) and/or CD38 were evaluated. Results. HCV-positive viremic women had a statistically significantly higher percentage of activated CD8 T cells (P<.001) and a statistically significantly higher incidence of AIDS compared with HCV-negative women (P<.001 [log-rank test]). The AIDS risk was greater among HCV-positive viremic women in the highest tertile compared with the lowest tertile (>43% vs <26%) of CD8(+)CD38(+)DR(+) T cells (hazard ratio, 2.94 [95% confidence interval, 1.50-5.77]; P<.001). This difference was not observed in the HCV-negative women (hazard ratio, 1.87 [95% confidence interval, 0.80-4.35]; P = .16). In contrast, CD4 activation predicted AIDS in both groups similarly. Increased percentages of CD8(+)CD38(-)DR(+), CD4(+)CD38(-)DR(-), and CD8(+)CD38(-)DR(-) T cells were associated with a 160% decreased risk of AIDS for HCV-positive viremic women and HCV-negative women. Conclusion. HCV-positive viremic women with HIV coinfection who have high levels of T cell activation may have increased risk of AIDS. Earlier treatment of HIV and HCV infection may be beneficial. C1 [Kovacs, Andrea] Univ So Calif, Maternal Child & Adolescent Ctr Infect Dis & Viro, Keck Sch Med, HRA 300, Los Angeles, CA 90033 USA. [Karim, Roksana; Mack, Wendy J.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA. [Tien, Phyllis C.; Al-Harthi, Lena] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tien, Phyllis C.; Al-Harthi, Lena] San Francisco VA Med Ctr, San Francisco, CA USA. [Landay, Alan; Voris, John] Rush Univ, Dept Immunol & Microbiol, Med Ctr, Chicago, IL 60612 USA. [Young, Mary A.] Georgetown Univ, Div Infect Dis, Washington, DC USA. [Augenbraun, Michael] Suny Downstate Coll Med, Dept Med, Brooklyn, NY USA. [Strickler, Howard D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Kovacs, A (reprint author), Univ So Calif, Maternal Child & Adolescent Ctr Infect Dis & Viro, Keck Sch Med, HRA 300, 1640 Marengo St, Los Angeles, CA 90033 USA. EM akovacs@usc.edu FU National Institute of Allergy and Infectious Diseases [R01-A1052065-04, R01-AI057006]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources [UL1 RR024131]; [U01-AI-35004]; [U01-AI-31834]; [U01-AI-34994]; [U01-AI-34989]; [U01-AI-34993]; [U01-AI-42590]; [K23 AI-66943] FX Financial support: National Institute of Allergy and Infectious Diseases (grant R01-A1052065-04 to A. K.; grant R01-AI057006 to H. S.; grants U01-AI-35004, U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-AI-34993, and U01-AI-42590 to the Women's Interagency HIV Study [WIHS]; and grant K23 AI-66943 to P. C. T.); Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant U01-HD-32632 to the WIHS); National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI grant UL1 RR024131). NR 50 TC 46 Z9 48 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 15 PY 2010 VL 201 IS 6 BP 823 EP 834 DI 10.1086/650997 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 557JH UT WOS:000274664900005 PM 20151840 ER PT J AU Singh, A Ye, M Bucur, O Zhu, SD Santos, MT Rabinovitz, I Wei, WY Gao, DM Hahn, WC Khosravi-Far, R AF Singh, Amrik Ye, Min Bucur, Octavian Zhu, Shudong Santos, Maria Tanya Rabinovitz, Isaac Wei, Wenyi Gao, Daming Hahn, William C. Khosravi-Far, Roya TI Protein Phosphatase 2A Reactivates FOXO3a through a Dynamic Interplay with 14-3-3 and AKT SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; PROMOTES TUMORIGENESIS; NUCLEAR EXCLUSION; SURVIVAL SIGNALS; KINASE B; PHOSPHORYLATION; PP2A; INHIBITION; APOPTOSIS; FAMILY AB Forkhead box transcription factor FOXO3a, a key regulator of cell survival, is regulated by reversible phosphorylation and subcellular localization. Although the kinases regulating FOXO3a activity have been characterized, the role of protein phosphatases (PP) in the control of FOXO3a subcellular localization and function is unknown. In this study, we detected a robust interaction between FOXO3a and PP2A. We further demonstrate that 14-3-3, while not impeding the interaction between PP2A and FOXO3a, restrains its activity toward AKT phosphorylation sites T32/S253. Disruption of PP2A function revealed that after AKT inhibition, PP2A-mediated dephosphorylation of T32/S253 is required for dissociation of 14-3-3, nuclear translocation, and transcriptional activation of FOXO3a. Our findings reveal that distinct phosphatases dephosphorylate conserved AKT motifs within the FOXO family and that PP2A is entwined in a dynamic interplay with AKT and 14-3-3 to directly regulate FOXO3a subcellular localization and transcriptional activation. C1 [Singh, Amrik; Ye, Min; Bucur, Octavian; Zhu, Shudong; Santos, Maria Tanya; Rabinovitz, Isaac; Wei, Wenyi; Gao, Daming; Khosravi-Far, Roya] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Singh, Amrik; Ye, Min; Bucur, Octavian; Zhu, Shudong; Santos, Maria Tanya; Rabinovitz, Isaac; Wei, Wenyi; Gao, Daming; Khosravi-Far, Roya] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hahn, William C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hahn, William C.] MIT, Cambridge, MA 02142 USA. [Hahn, William C.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. RP Khosravi-Far, R (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. EM rkhosrav@bidmc.harvard.edu RI Bucur, Octavian/G-2823-2010 OI Bucur, Octavian/0000-0002-8501-588X FU U.S. Public Health Service [CA131664, CA105306, 2-T32-HL07623-22, 5-F32-CA132365-02]; Lady Tata Memorial Trust FX We thank Joseph Avruch (Massachusetts General Hospital/Harvard Medical School), Azad Bonni (Harvard Medical School), Boudewijn Burgering (University Medical Center Utrecht), James Griffin (Dana Farber Cancer Institute/Harvard Medical School), Kun-Liang Guan (University of California, San Diego Medical Center), Marc Mumby (University of Texas Southwestern Medical Center), and William Sellers (Novartis Institutes for BioMedical Research) for reagents. We are grateful to Jack Lawler and Susan Glueck for critical reading of the manuscript. This work was supported by U.S. Public Health Service grants CA131664 and CA105306 (to R. K.), 2-T32-HL07623-22 and 5-F32-CA132365-02 (to A. S.), and a Lady Tata Memorial Trust Award (to O. B.). NR 41 TC 45 Z9 46 U1 2 U2 6 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR 15 PY 2010 VL 21 IS 6 BP 1140 EP 1152 DI 10.1091/mbc.E09-09-0795 PG 13 WC Cell Biology SC Cell Biology GA 567GQ UT WOS:000275433500026 PM 20110348 ER PT J AU Nelson, KP Edwards, D AF Nelson, Kerrie P. Edwards, Don TI Improving the reliability of diagnostic tests in population-based agreement studies SO STATISTICS IN MEDICINE LA English DT Article DE agreement, model-based kappa, Cohen's kappa; intraclass kappa, generalized linear mixed model; crossed random effects ID INTERRATER AGREEMENT; MAMMOGRAPHY; KAPPA; MODEL; VARIABILITY; CLASSIFICATIONS; ASSOCIATION; PERFORMANCE; CARCINOMA; RATINGS AB Many large-scale studies have recently been carried out to assess the reliability of diagnostic procedures, such as mammography for the detection of breast cancer. The large numbers of raters and subjects involved raise new challenges in how to measure agreement in these types of studies. An important motivator of these studies is the identification of factors that contribute to the often wide discrepancies observed between raters' classifications, such as a rater's experience, in order to improve the reliability of the diagnostic process of interest. Incorporating covariate information into the agreement model is a key component in addressing these questions. Few agreement models are currently available that jointly model larger numbers of raters and subjects and incorporate covariate information. In this paper, we extend a recently developed population-based model and measure of agreement for binary ratings to incorporate covariate information using the class of generalized linear mixed models with a probit link function. Important information on factors related to the subjects and raters can be included as fixed and/or random effects in the model. We demonstrate how agreement can be assessed between subgroups of the raters and/or subjects, for example, comparing agreement between experienced and less experienced raters. Simulation studies are carried out to test the performance of the proposed models and measures of agreement. Application to a large-scale breast cancer study is presented. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Nelson, Kerrie P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nelson, Kerrie P.] Harvard Univ, Sch Med, Ctr Biostat, Boston, MA 02114 USA. [Edwards, Don] Univ S Carolina, Dept Stat, Columbia, SC 29208 USA. RP Nelson, KP (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Suite 560, Boston, MA 02114 USA. FU United States' Institutes of Health [R03CA114783-01A1] FX Contract/grant sponsor United States' Institutes of Health, contract/grant number R03CA114783-01A1 NR 34 TC 1 Z9 1 U1 4 U2 11 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 2010 VL 29 IS 6 BP 617 EP 626 DI 10.1002/sim.3819 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 570PW UT WOS:000275691200001 PM 20128018 ER PT J AU Reszka, N Zhou, CH Song, B Sodroski, JG Knipe, DM AF Reszka, Natalia Zhou, Changhong Song, Byeongwoon Sodroski, Joseph G. Knipe, David M. TI Simian TRIM5 alpha proteins reduce replication of herpes simplex virus SO VIROLOGY LA English DT Article DE HSV; TRIM5; Restriction ID PML NUCLEAR-BODIES; PROMYELOCYTIC LEUKEMIA PROTEIN; INFECTED-CELL PROTEIN-0; IMMUNODEFICIENCY-VIRUS; RETROVIRAL RESTRICTION; ANTIVIRAL DEFENSE; VIRAL REPLICATION; BINDING PROTEIN; AIDS VACCINE; MONKEY CELLS AB Old World monkey TRIM5 alpha proteins are known to block the replication of human immunodeficiency virus and other retroviruses in a species-specific fashion. In this report, we show that specific forms of simian TRIM5 alpha proteins can restrict herpes simplex virus (HSV) infection. To define the effect of TRIM5 alpha on HSV replication, we examined HSV infection in HeLa cell lines that stably express simian and human orthologs of TRIM5 alpha proteins. We demonstrated that several simian TRIM5 alpha proteins can restrict HSV replication, with the TRIM5a protein of rhesus macaques showing the strongest inhibition of HSV infection. We also found that the level of the inhibition of virus replication was viral strain-specific. TRIM5 alpha is likely to inhibit HSV at the early stage of infection; however, at later times of infection, the levels of TRIM5 alpha are significantly decreased. Thus, some TRIM5 alpha proteins exhibit antiviral effects that extend beyond retroviral infections, but HSV may be able to reduce this restriction by reducing TRIM5 alpha levels during the later phases of virus replication. Our results also argue that TRIM5 alpha is only part of the reduced level of HSV replication in rhesus macaques, which are known to be less susceptible to HSV infection than other primates. (C) 2009 Elsevier Inc. All rights reserved. C1 [Reszka, Natalia; Zhou, Changhong; Knipe, David M.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Song, Byeongwoon; Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div AIDS, Boston, MA 02115 USA. RP Knipe, DM (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. EM david_knipe@hms.harvard.edu FU NIH HIVRAD [AI46006]; NIH [AI63987] FX We thank Anna Cliffe for comments on the manuscript. This research was supported by NIH HIVRAD grant AI46006 (DMK) and NIH grant AI63987 (JS). NR 57 TC 6 Z9 6 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 MAR 15 PY 2010 VL 398 IS 2 BP 243 EP 250 DI 10.1016/j.virol.2009.11.041 PG 8 WC Virology SC Virology GA 557KZ UT WOS:000274669300012 PM 20060996 ER PT J AU Kennerson, ML Nicholson, GA Kaler, SG Kowalski, B Mercer, JFB Tang, JR Llanos, RM Chu, SN Takata, RI Speck-Martins, CE Baets, J Almeida-Souza, L Fischer, D Timmerman, V Taylor, PE Scherer, SS Ferguson, TA Bird, TD De Jonghe, P Feely, SME Shy, ME Garbern, JY AF Kennerson, Marina L. Nicholson, Garth A. Kaler, Stephen G. Kowalski, Bartosz Mercer, Julian F. B. Tang, Jingrong Llanos, Roxana M. Chu, Shannon Takata, Reinaldo I. Speck-Martins, Carlos E. Baets, Jonathan Almeida-Souza, Leonardo Fischer, Dirk Timmerman, Vincent Taylor, Philip E. Scherer, Steven S. Ferguson, Toby A. Bird, Thomas D. De Jonghe, Peter Feely, Shawna M. E. Shy, Michael E. Garbern, James Y. TI Missense Mutations in the Copper Transporter Gene ATP7A Cause X-Linked Distal Hereditary Motor Neuropathy SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SPINAL MUSCULAR-ATROPHY; OCCIPITAL-HORN-SYNDROME; MARIE-TOOTH-DISEASE; MENKES-DISEASE; NEURON DISEASE; CANDIDATE GENE; DEFICIENCY MYELONEUROPATHY; WILSON-DISEASE; PROTEIN; TRAFFICKING AB Distal hereditary motor neuropathies comprise a clinically and genetically heterogeneous group of disorders. We recently mapped an X-linked form of this condition to chromosome Xq13.1-q21 in two large unrelated families. The region of genetic linkage included ATP7A, which encodes a copper-transporting P-type ATPase mutated in patients with Menkes disease, a severe infantile-onset neurodegenerative condition. We identified two unique ATP7A missense mutations (p.P1386S and p.T9941) in males with distal motor neuropathy in two families. These molecular alterations impact highly conserved amino acids in the carboxyl half of ATP7A and do not directly involve the copper transporter's known critical functional domains. Studies of p.P1386S revealed normal ATP7A mRNA and protein levels, a defect in ATP7A trafficking, and partial rescue of a S. cerevisiae copper transport knockout. Although ATP7A mutations are typically associated with severe Menkes disease or its milder allelic variant, occipital horn syndrome, we demonstrate here that certain missense mutations at this locus can cause a syndrome restricted to progressive distal motor neuropathy without overt signs of systemic copper deficiency. This previously unrecognized genotype-phenotype correlation suggests an important role of the ATP7A copper transporter in motor-neuron maintenance and function. C1 [Kennerson, Marina L.; Nicholson, Garth A.; Kowalski, Bartosz; Chu, Shannon] Univ Sydney, ANZAC Res Inst, Northcott Neurosci Lab, Concord, Australia. [Kennerson, Marina L.; Nicholson, Garth A.] Concord Hosp, Mol Med Lab, Concord, Australia. [Kaler, Stephen G.; Tang, Jingrong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD USA. [Mercer, Julian F. B.; Llanos, Roxana M.; Taylor, Philip E.] Deakin Univ, Sch Life & Environm Sci, Ctr Cellular & Mol Biol, Burwood, Australia. [Takata, Reinaldo I.; Speck-Martins, Carlos E.] Sarah Network Rehabil Hosp, Brasilia, DF, Brazil. [Baets, Jonathan; Almeida-Souza, Leonardo; Timmerman, Vincent; De Jonghe, Peter] Flanders Inst Biotechnol, Dept Mol Genet, Antwerp, Belgium. [Baets, Jonathan; Almeida-Souza, Leonardo; Timmerman, Vincent; De Jonghe, Peter] Univ Antwerp, B-2020 Antwerp, Belgium. [Fischer, Dirk] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland. [Fischer, Dirk] Univ Childrens Hosp Basel, Dept Neuropediat, Basel, Switzerland. [Scherer, Steven S.; Ferguson, Toby A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Bird, Thomas D.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Bird, Thomas D.] Univ Washington, Sch Med, Dept Med Genet, Seattle, WA USA. [Bird, Thomas D.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Feely, Shawna M. E.; Shy, Michael E.; Garbern, James Y.] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. [Feely, Shawna M. E.; Shy, Michael E.; Garbern, James Y.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Kennerson, ML (reprint author), Univ Sydney, ANZAC Res Inst, Northcott Neurosci Lab, Concord, Australia. EM marinak@anzac.edu.au RI Almeida-Souza, Leonardo/C-3437-2011; Kennerson, Marina/B-5058-2014 FU Motor Neuron Disease Research Institute of Australia; National Health and Medical Research Council of Australia; Intramural Research program of the National Institute of Child Health and Human Development; Methusalem project of the University of Antwerp; Fund for Scientific Research (FWO-Flanders); Medical Foundation Queen Elisabeth (GSKE); Interuniversity Attraction Poles program [P6/43]; Belgian Federal Science Policy Office (BELSPO) FX We thank the patients and family members for their participation in this study. We thank Rabia Chaudhry and Alison Blake for their assistance with Cell Cultures and Jose Centeno for fibroblast copper measurements. This work was supported by grants from the Motor Neuron Disease Research Institute of Australia, the National Health and Medical Research Council of Australia, the Intramural Research program of the National Institute of Child Health and Human Development, the Methusalem project of the University of Antwerp, the Fund for Scientific Research (FWO-Flanders), the Medical Foundation Queen Elisabeth (GSKE), and the Interuniversity Attraction Poles program (P6/43) of the Belgian Federal Science Policy Office (BELSPO). J.B. and L.S. are Supported by PhD fellowships of the FWO-Flanders and the University of Antwerp, respectively. We thank Professor David Handelsman for his useful constructive comments on the manuscript. NR 47 TC 79 Z9 81 U1 0 U2 4 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 MAR 12 PY 2010 VL 86 IS 3 BP 343 EP 352 DI 10.1016/j.ajhg.2010.01.027 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 570LG UT WOS:000275678800006 PM 20170900 ER PT J AU Hu, W Xu, RJ Sun, W Szulc, ZM Bielawski, J Obeid, LM Mao, CG AF Hu, Wei Xu, Ruijuan Sun, Wei Szulc, Zdzislaw M. Bielawski, Jacek Obeid, Lina M. Mao, Cungui TI Alkaline Ceramidase 3 (ACER3) Hydrolyzes Unsaturated Long-chain Ceramides, and Its Down-regulation Inhibits Both Cell Proliferation and Apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MOLECULAR-CLONING; ACID CERAMIDASE; FUNCTIONAL-CHARACTERIZATION; MITOCHONDRIAL CERAMIDASE; SACCHAROMYCES-CEREVISIAE; FARBER-DISEASE; CANCER CELLS; SPHINGOSINE; GENERATION AB Ceramides with different fatty acyl chains may vary in their physiological or pathological roles; however, it remains unclear how cellular levels of individual ceramide species are regulated. Here, we demonstrate that our previously cloned human alkaline ceramidase 3 (ACER3) specifically controls the hydrolysis of ceramides carrying unsaturated long acyl chains, unsaturated long-chain (ULC) ceramides. In vitro, ACER3 only hydrolyzed C(18:1)-, C(20:1)-, C(20:4)-ceramides, dihydroceramides, and phytoceramides. In cells, ACER3 overexpression decreased C(18:1)- and C(20:1)-ceramides and dihydroceramides, whereas ACER3 knockdown by RNA interference had the opposite effect, suggesting that ACER3 controls the catabolism of ULC ceramides and dihydroceramides. ACER3 knockdown inhibited cell proliferation and up-regulated the cyclin-dependent kinase inhibitor p21(CIP1/WAF1). Blocking p21(CIP1/WAF1) up-regulation attenuated the inhibitory effect of ACER3 knockdown on cell proliferation, suggesting that ACER3 knockdown inhibits cell proliferation because of p21(CIP1/WAF1) up-regulation. ACER3 knockdown inhibited cell apoptosis in response to serum deprivation. ACER3 knockdown up-regulated the expression of the alkaline ceramidase 2 (ACER2), and the ACER2 up-regulation decreased non-ULC ceramide species while increasing both sphingosine and its phosphate. Collectively, these data suggest that ACER3 catalyzes the hydrolysis of ULC ceramides and dihydroceramides and that ACER3 coordinates with ACER2 to regulate cell proliferation and survival. C1 [Mao, Cungui] Med Univ S Carolina, Div Gen Internal Med, Dept Med, Charleston, SC 29425 USA. [Szulc, Zdzislaw M.; Bielawski, Jacek; Obeid, Lina M.; Mao, Cungui] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Hosp, Charleston, SC 29425 USA. RP Mao, CG (reprint author), Med Univ S Carolina, Div Gen Internal Med, Dept Med, 114 Doughty St,Rm 646,STB,POB 250779, Charleston, SC 29425 USA. EM maoc@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [P20RR017677, R01CA104834, R01GM062887]; Veterans Affairs Merit award FX This work was supported, in whole or in part, by National Institutes of Health Grants P20RR017677 (to C.M.), R01CA104834 (to C.M.), and R01GM062887 (to L.M.O.). This work was also supported by a Veterans Affairs Merit award (to L.M.O.). NR 42 TC 31 Z9 31 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 2010 VL 285 IS 11 BP 7964 EP 7976 DI 10.1074/jbc.M109.063586 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 567AE UT WOS:000275413800014 PM 20068046 ER PT J AU Zlotoff, DA Sambandam, A Logan, TD Bell, JJ Schwarz, BA Bhandoola, A AF Zlotoff, Daniel A. Sambandam, Arivazhagan Logan, Theodore D. Bell, J. Jeremiah Schwarz, Benjamin A. Bhandoola, Avinash TI CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus SO BLOOD LA English DT Article ID T-CELL DEVELOPMENT; COMMON LYMPHOID PROGENITORS; MOUSE BONE-MARROW; STEM-CELLS; LINEAGE COMMITMENT; UP-REGULATION; PRECURSORS; IDENTIFICATION; EXPRESSION; BLOOD AB T lymphopoiesis requires settling of the thymus by bone marrow-derived precursors throughout adult life. Progenitor entry into the thymus is selective, but the molecular basis of this selectivity is incompletely understood. The chemokine receptor CCR9 has been demonstrated to be important in this process. However, progenitors lacking CCR9 can still enter the thymus, suggesting a role for additional molecules. Here we report that the chemokine receptor CCR7 is also required for efficient thymic settling. CCR7 is selectively expressed on bone marrow progenitors previously shown to have the capacity to settle the thymus, and CCR7(-/-) progenitors are defective in settling the thymus. We further demonstrate that CCR7 sustains thymic settling in the absence of CCR9. Mice deficient for both CCR7 and CCR9 have severe reductions in the number of early thymic progenitors, and in competitive assays CCR7(-/-) CCR9(-/-) double knockout progenitors are almost completely restricted from thymic settling. However, these mice possess near-normal thymic cellularity. Compensatory expansion of intrathymic populations can account for at least a part of this recovery. Together our results illustrate the critical role of chemokine receptor signaling in thymic settling and help to clarify the cellular identity of the physiologic thymic settling progenitors. (Blood. 2010; 115: 1897-1905) C1 [Zlotoff, Daniel A.; Logan, Theodore D.; Bell, J. Jeremiah; Bhandoola, Avinash] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Sambandam, Arivazhagan] Genentech Inc, San Francisco, CA 94080 USA. [Schwarz, Benjamin A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Bhandoola, A (reprint author), 266 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM bhandooa@mail.med.upenn.edu FU NIH [AI080091, AI059621, HL086900, RC1HL099758]; Leukemia & Lymphoma Society FX This work was supported by NIH grants AI080091 (J.J.B.), AI059621, HL086900, and RC1HL099758 (A. B.), and a Scholar Award from the Leukemia & Lymphoma Society (A. B.). NR 50 TC 99 Z9 100 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 11 PY 2010 VL 115 IS 10 BP 1897 EP 1905 DI 10.1182/blood-2009-08-237784 PG 9 WC Hematology SC Hematology GA 571KS UT WOS:000275751300011 PM 19965655 ER PT J AU Hasserjian, RP Zuo, Z Garcia, C Tang, GL Kasyan, A Luthra, R Abruzzo, LV Kantarjian, HM Medeiros, LJ Wang, SA AF Hasserjian, Robert P. Zuo, Zhuang Garcia, Christine Tang, Guilin Kasyan, Armen Luthra, Rajyalakshmi Abruzzo, Lynne V. Kantarjian, Hagop M. Medeiros, L. Jeffrey Wang, Sa A. TI Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROMES; ACUTE ERYTHROLEUKEMIA; REFRACTORY-ANEMIA; BONE-MARROW; BLASTS; RECLASSIFICATION; PROPOSALS; MUTATIONS; PROGNOSIS AB Acute erythroid leukemia (AEL) is a rare type of acute myeloid leukemia (AML) for which diagnostic criteria have been refined in the 2008 World Health Organization (WHO) classification of AML. The relationship of AEL to myelodysplastic syndromes (MDSs) and to AML with myelodysplasia-related changes (AMLMRC) is not clearly defined. We conducted a retrospective, multi-institutional study of patients with AEL and compared them with patients with MDS or AML-MRC with erythroid hyperplasia (>= 50% erythroid cells). Among a total of 124 patients with AEL, 32% had a history of MDS or chronic cytopenia, 32% had therapy-related disease, and 35% had de novo disease. Sixty-four percent of patients had unfavorable AML risk-group karyotypes. FLT3 and RAS mutations were infrequent, occurring in 6% and 2%, respectively. The median overall survival (OS) of all AEL patients was 8 months, comparable with that of patients with MDS or AML-MRC with erythroid hyperplasia. The OS was related to cytogenetic risk group, but not blast count or morphologic dysplasia. Our findings suggest that AEL is in the continuum of MDS and AML with erythroid hyperplasia, where karyotype rather than an arbitrary blast cutoff represents the most important prognostic factor. (Blood. 2010; 115: 1985-1992) C1 [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zuo, Zhuang; Kasyan, Armen; Luthra, Rajyalakshmi; Abruzzo, Lynne V.; Medeiros, L. Jeffrey; Wang, Sa A.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Garcia, Christine] Univ Pittsburgh, Sch Med, Dept Pathol, Div Hematopathol, Pittsburgh, PA 15260 USA. [Tang, Guilin] Univ Massachusetts, Mem Med Ctr, Dept Pathol, Worcester, MA 01605 USA. [Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Dept Hematol, Houston, TX 77030 USA. RP Hasserjian, RP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM rhasserjian@partners.org FU National Center for Research Resources (NCRR) [UL1 RR024153]; National Institutes of Health (NIH); NIH Roadmap for Medical Research FX This publication was made possible by grant no. UL1 RR024153 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or NIH. NR 26 TC 48 Z9 50 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 MAR 11 PY 2010 VL 115 IS 10 BP 1985 EP 1992 DI 10.1182/blood-2009-09-243964 PG 8 WC Hematology SC Hematology GA 571KS UT WOS:000275751300021 PM 20040759 ER PT J AU Virgin, HW Walker, BD AF Virgin, Herbert W. Walker, Bruce D. TI Immunology and the elusive AIDS vaccine SO NATURE LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CHRONIC VIRAL-INFECTION; T-CELL RESPONSES; HIV-1 INFECTION; NEUTRALIZING ANTIBODIES; HETEROLOGOUS CHALLENGE; ANTIRETROVIRAL THERAPY; RETROVIRUS INFECTION; DISEASE PROGRESSION; LYMPHOCYTE ESCAPE AB Developing a human immunodeficiency virus (HIV) vaccine is critical to end the global acquired immunodeficiency syndrome (AIDS) epidemic, but many question whether this goal is achievable. Natural immunity is not protective, and despite immunogenicity of HIV vaccine candidates, human trials have exclusively yielded disappointing results. Nevertheless, there is an indication that success may be possible, but this will be dependent on understanding the antiviral immune response in unprecedented depth to identify and engineer the types of immunity required. Here we outline fundamental immunological questions that need to be answered to develop a protective HIV vaccine, and the immediate need to harness a much broader scientific community to achieve this goal. C1 [Virgin, Herbert W.] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Virgin, Herbert W.] Washington Univ, Midwest Reg Ctr Excellence Biodef & Emerging Infe, St Louis, MO 63110 USA. [Walker, Bruce D.] Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA 02129 USA. [Walker, Bruce D.] Harvard Univ, Howard Hughes Med Inst, Charlestown, MA 02129 USA. RP Virgin, HW (reprint author), Washington Univ, Sch Med, Campus Box 8118,660 S Euclid Ave, St Louis, MO 63110 USA. EM virgin@wustl.edu; bwalker@partners.org FU National Institutes of Health; Bill and Melinda Gates Foundation; Mark and Lisa Schwartz Foundation FX We would like to acknowledge, while accepting full responsibility for the content and opinions expressed, open discussions and correspondence with: M. Altfeld, D. Brooks, D. Burton, M. Colonna, L. Corey, B. Beutler, D. Barouch, A. Chakraborty, F. Chisari, R. Desrosiers, M. Diamond, A. Garcia-Sastre, L. Glimcher, P. Goulder, H. Greenberg, A. Haase, K. Hasenkrug, B. Haynes, M. Hirsch, S. Abdool-Karim, W. Koff, B. Lamb, J. Lifson, J. Loh, R. Medzhitov, J. Moore, M. Nussenzweig, M. Oldstone, L. Picker, B. Roizman, R. Siliciano, G. Silvestri, S. Wain-Hobson, D. Watkins, R. Weiss, J. Wherry and O. Yang. This work was supported by grants from the National Institutes of Health (H. W. V. and B. D. W.), the Bill and Melinda Gates Foundation (B. D. W.), and a gift from the Mark and Lisa Schwartz Foundation (B. D. W.). NR 101 TC 108 Z9 109 U1 3 U2 11 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 MAR 11 PY 2010 VL 464 IS 7286 BP 224 EP 231 DI 10.1038/nature08898 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 566JO UT WOS:000275366100036 PM 20220841 ER PT J AU Hare, S Gupta, SS Valkov, E Engelman, A Cherepanov, P AF Hare, Stephen Gupta, Saumya Shree Valkov, Eugene Engelman, Alan Cherepanov, Peter TI Retroviral intasome assembly and inhibition of DNA strand transfer SO NATURE LA English DT Article ID AUTOMATED STRUCTURE SOLUTION; SARCOMA-VIRUS INTEGRASE; HIV-1 INTEGRASE; CRYSTAL-STRUCTURE; ACTIVE-SITE; ENZYMATIC-ACTIVITY; TERMINAL DOMAINS; STRUCTURAL BASIS; BINDING DOMAIN; PROTEIN AB Integrase is an essential retroviral enzyme that binds both termini of linear viral DNA and inserts them into a host cell chromosome. The structure of full-length retroviral integrase, either separately or in complex with DNA, has been lacking. Furthermore, although clinically useful inhibitors of HIV integrase have been developed, their mechanism of action remains speculative. Here we present a crystal structure of full-length integrase from the prototype foamy virus in complex with its cognate DNA. The structure shows the organization of the retroviral intasome comprising an integrase tetramer tightly associated with a pair of viral DNA ends. All three canonical integrase structural domains are involved in extensive protein-DNA and protein-protein interactions. The binding of strand-transfer inhibitors displaces the reactive viral DNA end from the active site, disarming the viral nucleoprotein complex. Our findings define the structural basis of retroviral DNA integration, and will allow modelling of the HIV-1 intasome to aid in the development of antiretroviral drugs. C1 [Hare, Stephen; Gupta, Saumya Shree; Valkov, Eugene; Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Med, London W2 1PG, England. [Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Cherepanov, P (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Med, St Marys Campus,Norfolk Pl, London W2 1PG, England. EM p.cherepanov@imperial.ac.uk RI Valkov, Eugene/C-1554-2010; Cherepanov, Peter/F-6859-2010; OI Cherepanov, Peter/0000-0002-0634-538X; Hare, Stephen/0000-0003-2951-1595 FU UK Medical Research Council; US National Institutes of Health FX We thank F. Dyda for critical reading of the manuscript, R. Clayton and M. Cummings for the generous gift of InSTIs and helpful discussions, T. Sorensen and the staff of the I02 and I04 beamlines of the Diamond Light Source for assistance with X-ray data collection. P. C. and co-workers are funded by the UK Medical Research Council, and A. E. by the US National Institutes of Health. NR 50 TC 363 Z9 376 U1 5 U2 43 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 11 PY 2010 VL 464 IS 7286 BP 232 EP U108 DI 10.1038/nature08784 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 566JO UT WOS:000275366100037 PM 20118915 ER PT J AU Agarwal, S Loh, YH McLoughlin, EM Huang, JJ Park, IH Miller, JD Huo, HG Okuka, M dos Reis, RM Loewer, S Ng, HH Keefe, DL Goldman, FD Klingelhutz, AJ Liu, L Daley, GQ AF Agarwal, Suneet Loh, Yuin-Han McLoughlin, Erin M. Huang, Junjiu Park, In-Hyun Miller, Justine D. Huo, Hongguang Okuka, Maja dos Reis, Rosana Maria Loewer, Sabine Ng, Huck-Hui Keefe, David L. Goldman, Frederick D. Klingelhutz, Aloysius J. Liu, Lin Daley, George Q. TI Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients SO NATURE LA English DT Article ID REPLICATIVE LIFE-SPAN; HUMAN SOMATIC-CELLS; HUMAN BONE-MARROW; HEMATOPOIETIC-CELLS; HUMAN FIBROBLASTS; GENE-EXPRESSION; DEFINED FACTORS; RNA COMPONENT; MAINTENANCE; MUTATIONS AB Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer degeneration of multiple tissues(1-3). Patient-specific induced pluripotent stem (iPS) cells(4) represent invaluable in vitro models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity, which is accompanied by induction of the telomerase reverse transcriptase gene (TERT)(5-7). We investigated whether defects in telomerase function would limit derivation and maintenance of iPS cells from patients with DC. Here we show that reprogrammed DC cells overcome a critical limitation in telomerase RNA component (TERC) levels to restore telomere maintenance and self-renewal. We discovered that TERC upregulation is a feature of the pluripotent state, that several telomerase components are targeted by pluripotency-associated transcription factors, and that in autosomal dominant DC, transcriptional silencing accompanies a 3' deletion at the TERC locus. Our results demonstrate that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting telomerase, and show that strategies to increase TERC expression may be therapeutically beneficial in DC patients. C1 [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Huang, Junjiu; Okuka, Maja; dos Reis, Rosana Maria; Keefe, David L.; Liu, Lin] Univ S Florida, Coll Med, Dept Obstet & Gynecol, MDC 3125, Tampa, FL 33612 USA. [Huang, Junjiu] Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Guangzhou 510275, Guangdong, Peoples R China. [Ng, Huck-Hui] Genome Inst Singapore, Gene Regulatory Lab, Singapore 138672, Singapore. [Ng, Huck-Hui] Natl Univ Singapore, Dept Biol Sci, Singapore 138672, Singapore. [Goldman, Frederick D.] Childrens Hosp Alabama, Dept Pediat, Birmingham, AL 35233 USA. [Klingelhutz, Aloysius J.] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. [Liu, Lin] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China. [Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu RI Reis, Rosana/E-3346-2012; Ng, Huck Hui/A-1135-2009; Saude da mulher, Inct/J-9403-2013; Loh, Yuin-Han/E-1096-2014; OI Reis, Rosana/0000-0001-9631-4167; Loh, Yuin-Han/0000-0002-4715-6454; NG, HUCK HUI/0000-0001-6352-8417 FU National Institutes of Health (NIH) [K08HL089150, R01AG0227388]; Manton Center for Orphan Disease Research; Amy Clare Potter Fellowship; Agency of Science, Technology and Research; Institute of Medical Biology, Singapore; James and Esther King Biomedical Research Program; MOST 973 project [2009CB941000] FX This work was funded by grants from the National Institutes of Health (NIH) and the Manton Center for Orphan Disease Research (G. Q. D.); NIH K08HL089150, Amy Clare Potter Fellowship and Manton Center for Orphan Disease Research (S. A.); the Agency of Science, Technology and Research and the Institute of Medical Biology, Singapore (Y.-H. L.); NIH R01AG0227388 (F. D. G. and A. J. K.); and the James and Esther King Biomedical Research Program and MOST 973 project (2009CB941000) (D. L. K and L. L). NR 38 TC 162 Z9 165 U1 4 U2 43 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 11 PY 2010 VL 464 IS 7286 BP 292 EP U176 DI 10.1038/nature08792 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 566JO UT WOS:000275366100050 PM 20164838 ER PT J AU Ropper, AH Raje, NS Lawrimore, TM Camelo-Piragua, S Sohani, AR AF Ropper, Allan H. Raje, Noopur S. Lawrimore, Tara M. Camelo-Piragua, Sandra Sohani, Aliyah R. TI A Man with Peripheral Neuropathy and Ascites The POEMS syndrome, with demyelinating neuropathy and solitary plasmacytoma of bone SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; STEM-CELL TRANSPLANTATION; CROW-FUKASE-SYNDROME; OF-THE-LITERATURE; BEVACIZUMAB THERAPY; POLYNEUROPATHY; DYSCRASIA; VEGF C1 [Ropper, Allan H.] Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. [Raje, Noopur S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lawrimore, Tara M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Camelo-Piragua, Sandra; Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ropper, Allan H.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Raje, Noopur S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lawrimore, Tara M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Camelo-Piragua, Sandra; Sohani, Aliyah R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ropper, AH (reprint author), Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. NR 23 TC 7 Z9 9 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 MAR 11 PY 2010 VL 362 IS 10 BP 929 EP 940 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 566JM UT WOS:000275365900015 PM 20220188 ER PT J AU Drazen, JM Weinstein, DF AF Drazen, Jeffrey M. Weinstein, Debra F. TI Considering Recertification SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Drazen, Jeffrey M.; Weinstein, Debra F.] Partners HealthCare Syst, Off Grad Med Educ, Boston, MA USA. [Weinstein, Debra F.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Weinstein, Debra F.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Weinstein, Debra F.] Harvard Univ, Sch Med, Boston, MA USA. RP Drazen, JM (reprint author), Partners HealthCare Syst, Off Grad Med Educ, Boston, MA USA. OI Drazen, Jeffrey/0000-0003-2715-9890 NR 2 TC 30 Z9 30 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 11 PY 2010 VL 362 IS 10 BP 946 EP 947 DI 10.1056/NEJMe1000174 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 566JM UT WOS:000275365900018 PM 20220191 ER PT J AU Levinson, W King, TE Goldman, L Goroll, AH Kessler, B AF Levinson, Wendy King, Talmadge E., Jr. Goldman, Lee Goroll, Allan H. Kessler, Bruce TI American Board of Internal Medicine Maintenance of Certification Program SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; QUALITY IMPROVEMENT; SELF-ASSESSMENT; UNITED-STATES; HEALTH-CARE; PHYSICIANS; EXPERIENCE; RECERTIFICATION; EDUCATION; ADULTS C1 [Levinson, Wendy] Univ Toronto, Dept Med, Toronto, ON, Canada. [King, Talmadge E., Jr.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Goldman, Lee] Columbia Univ, Med Ctr, New York, NY USA. [Goroll, Allan H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goroll, Allan H.] Harvard Univ, Sch Med, Boston, MA USA. [Kessler, Bruce] Eureka Internal Med, Eureka, CA USA. RP Levinson, W (reprint author), Univ Toronto, Dept Med, Toronto, ON, Canada. NR 17 TC 40 Z9 40 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 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 11 PY 2010 VL 362 IS 10 BP 948 EP 952 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 566JM UT WOS:000275365900019 PM 20220192 ER PT J AU Choy, E AF Choy, Edwin TI A Man with Cough, Hoarseness, and Abnormalities on Chest Imaging REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID EWING SARCOMA; TEMOZOLOMIDE; IRINOTECAN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Choy, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 11 PY 2010 VL 362 IS 10 BP 961 EP 961 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 566JM UT WOS:000275365900033 ER PT J AU Poage, GM Christensen, BC Houseman, EA McClean, MD Wiencke, JK Posner, MR Clark, JR Nelson, HH Marsit, CJ Kelsey, KT AF Poage, Graham M. Christensen, Brock C. Houseman, E. Andres McClean, Michael D. Wiencke, John K. Posner, Marshall R. Clark, John R. Nelson, Heather H. Marsit, Carmen J. Kelsey, Karl T. TI Genetic and Epigenetic Somatic Alterations in Head and Neck Squamous Cell Carcinomas Are Globally Coordinated but Not Locally Targeted SO PLOS ONE LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; DNA METHYLATION; COPY NUMBER; PROMOTER METHYLATION; HIGH-RESOLUTION; CANCER PATIENTS; POOR-PROGNOSIS; BREAST-CANCER; SURVIVAL; ARRAY AB Background: Solid tumors, including head and neck squamous cell carcinomas (HNSCC), arise as a result of genetic and epigenetic alterations in a sustained stress environment. Little work has been done that simultaneously examines the spectrum of both types of changes in human tumors on a genome-wide scale and results so far have been limited and mixed. Since it has been hypothesized that epigenetic alterations may act by providing the second carcinogenic hit in gene silencing, we sought to identify genome-wide DNA copy number alterations and CpG dinucleotide methylation events and examine the global/local relationships between these types of alterations in HNSCC. Methodology/Principal Findings: We have extended a prior analysis of 1,413 cancer-associated loci for epigenetic changes in HNSCC by integrating DNA copy number alterations, measured at 500,000 polymorphic loci, in a case series of 19 primary HNSCC tumors. We have previously demonstrated that local copy number does not bias methylation measurements in this array platform. Importantly, we found that the global pattern of copy number alterations in these tumors was significantly associated with tumor methylation profiles (p<0.002). However at the local level, gene promoter regions did not exhibit a correlation between copy number and methylation (lowest q = 0.3), and the spectrum of genes affected by each type of alteration was unique. Conclusion/Significance: This work, using a novel and robust statistical approach demonstrates that, although a "second hit'' mechanism is not likely the predominant mode of action for epigenetic dysregulation in cancer, the patterns of methylation events are associated with the patterns of allele loss. Our work further highlights the utility of integrative genomics approaches in exploring the driving somatic alterations in solid tumors. C1 [Poage, Graham M.; Kelsey, Karl T.] Brown Univ, Dept Mol Pharmacol, Providence, RI 02912 USA. [Poage, Graham M.; Kelsey, Karl T.] Brown Univ, Dept Physiol, Providence, RI 02912 USA. [Christensen, Brock C.; Marsit, Carmen J.; Kelsey, Karl T.] Brown Univ, Dept Pathol, Providence, RI 02912 USA. [Christensen, Brock C.; Marsit, Carmen J.; Kelsey, Karl T.] Brown Univ, Dept Lab Med, Providence, RI 02912 USA. [Christensen, Brock C.; Houseman, E. Andres; Kelsey, Karl T.] Brown Univ, Dept Community Hlth, Ctr Environm Hlth & Technol, Providence, RI 02912 USA. [Houseman, E. Andres] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [McClean, Michael D.] Boston Univ, Dept Environm Hlth, Boston, MA 02215 USA. [Wiencke, John K.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Posner, Marshall R.] Dana Farber Canc Inst, Dept Med Oncol Solid Tumor Oncol, Boston, MA 02115 USA. [Clark, John R.] Massachusetts Gen Hosp, Dept Med Hematol Oncol, Boston, MA 02114 USA. [Nelson, Heather H.] Univ Minnesota, Mason Canc Ctr, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Poage, GM (reprint author), Brown Univ, Dept Mol Pharmacol, Providence, RI 02912 USA. EM Karl_Kelsey@Brown.edu RI Christensen, Brock/B-8460-2009; Kelsey, Karl/I-1252-2014; McClean, Michael/J-2934-2015 OI McClean, Michael/0000-0002-3902-8823; Houseman, Eugene Andres/0000-0003-0703-1830; Marsit, Carmen/0000-0003-4566-150X; FU Flight Attendant Medical Research Institute; National Institutes of Health [5R01CA078609-10, 2R01CA100679-06A1, 5RO1ES006717-13] FX This work was supported by Flight Attendant Medical Research Institute (C. M. and M. M.), and the National Institutes of Health (5R01CA078609-10, 2R01CA100679-06A1, 5RO1ES006717-13) (K.K. and J.W.). The funders had no role in study design, data collection, decision to publish, or preparation of the manuscript. NR 53 TC 20 Z9 20 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 MAR 11 PY 2010 VL 5 IS 3 AR e9651 DI 10.1371/journal.pone.0009651 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 569SJ UT WOS:000275620600007 PM 20300172 ER PT J AU Lee, BY Wiringa, AE Bailey, RR Lewis, GJ Feura, J Muder, RR AF Lee, Bruce Y. Wiringa, Ann E. Bailey, Rachel R. Lewis, G. Jonathan Feura, Jared Muder, Robert R. TI Staphylococcus aureus vaccine for orthopedic patients: An economic model and analysis SO VACCINE LA English DT Article DE Staphylococcus aureus; Vaccine; Orthopedic surgery; Economics; Computer simulation ID POLYSACCHARIDE CONJUGATE VACCINE; QUALITY-OF-LIFE; PASSIVE-IMMUNIZATION; TOTAL HIP; MRSA; INFECTIONS; SURGERY; UTILITY; IMMUNOTHERAPY; ARTHROPLASTY AB To evaluate the potential economic value of a Staphylococcus aureus vaccine for pre-operative orthopedic surgery patients, we developed an economic computer simulation model. At MRSA colonization rates as low as 1%, a $50 vaccine was cost-effective [<=$50,000 per quality-adjusted life year (QALY) saved] at vaccine efficacy >= 30%, and a $100 vaccine at vaccine efficacy >= 70%. High MASA prevalence (>= 25%) could justify a vaccine price as high as $1000. Our results suggest that a S. aureus vaccine for the pre-operative orthopedic population would be very cost-effective over a wide range of MASA prevalence and vaccine efficacies and costs. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Lee, Bruce Y.] Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA 15213 USA. [Lee, Bruce Y.; Wiringa, Ann E.; Bailey, Rachel R.; Lewis, G. Jonathan; Feura, Jared] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Lee, Bruce Y.; Wiringa, Ann E.; Bailey, Rachel R.; Lewis, G. Jonathan; Feura, Jared] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Muder, Robert R.] Univ Pittsburgh, Div Infect Dis, VA Pittsburgh Hlth Syst, Pittsburgh, PA 15213 USA. RP Lee, BY (reprint author), Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, Sect Decis Sci & Clin Syst Modeling, 200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA. EM BYL1@pitt.edu OI Slayton, Rachel/0000-0003-4699-8040 FU National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) [1U54GM088491-0109] FX Supported by the National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) through grant 1U54GM088491-0109. The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 15 Z9 15 U1 0 U2 1 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 MAR 11 PY 2010 VL 28 IS 12 BP 2465 EP 2471 DI 10.1016/j.vaccine.2009.12.075 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 576HN UT WOS:000276135200015 PM 20064479 ER PT J AU Burstein, HJ Sun, Y Dirix, LY Jiang, ZF Paridaens, R Tan, AR Awada, A Ranade, A Jiao, SC Schwartz, G Abbas, R Powell, C Turnbull, K Vermette, J Zacharchuk, C Badwe, R AF Burstein, Harold J. Sun, Yan Dirix, Luc Y. Jiang, Zefei Paridaens, Robert Tan, Antoinette R. Awada, Ahmad Ranade, Anantbhushan Jiao, Shunchang Schwartz, Gary Abbas, Richat Powell, Christine Turnbull, Kathleen Vermette, Jennifer Zacharchuk, Charles Badwe, Rajendra TI Neratinib, an Irreversible ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced ErbB2-Positive Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-II; ADJUVANT CHEMOTHERAPY; LAPATINIB MONOTHERAPY; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; SINGLE-AGENT; SOLID TUMORS; TRASTUZUMAB; EFFICACY; SAFETY AB Purpose Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer those with and those without prior trastuzumab treatment-in an open-label, multicenter, phase II trial. Patients and Methods Patients in the two cohorts (prior trastuzumab, n = 66; no prior trastuzumab, n = 70) received oral neratinib 240 mg once daily. The primary end point was the 16-week progression-free survival (PFS) rate for the evaluable population (prior trastuzumab, n = 63; no prior trastuzumab, n = 64), as assessed by independent review. Results The 16-week PFS rates were 59% for patients with prior trastuzumab treatment and 78% for patients with no prior trastuzumab treatment. Median PFS was 22.3 and 39.6 weeks, respectively. Objective response rates were 24% among patients with prior trastuzumab treatment and 56% in the trastuzumab-naive cohort. The most common adverse events were diarrhea, nausea, vomiting, and fatigue. Diarrhea was the most frequent grades 3 to 4 adverse event, occurring in 30% of patients with prior trastuzumab treatment and in 13% of patients with no prior trastuzumab treatment, which prompted dose reductions in 29% and 4% of patients, respectively, but treatment discontinuation in only one patient. No neratinib-related, grades 3 or 4 cardiotoxicity was reported. Conclusion Oral neratinib showed substantial clinical activity and was reasonably well tolerated among both heavily pretreated and trastuzumab-naive patients who had advanced, ErbB2-positive breast cancer. Diarrhea was the most common adverse effect but was manageable with antidiarrheal agents and dose modification. C1 [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA. Oncol Ctr AZ St Augustinus, Antwerp, Belgium. Univ Hosp Gasthuisberg, Leuven, Belgium. Inst Jules Bordet, B-1000 Brussels, Belgium. Chinese Acad Med Sci, Canc Hosp, Beijing, Peoples R China. Hosp Affiliated Acad Mil Med Sci, Beijing, Peoples R China. Canc Inst New Jersey, New Brunswick, NJ USA. Deenanath Mangeshkar Hosp, Pune, Maharashtra, India. Tata Mem Hosp, Mumbai 400012, Maharashtra, India. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Wyeth Ayerst Res, Cambridge, MA USA. Wyeth Ayerst Res, Collegeville, PA USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org FU Wyeth Research, Cambridge FX Supported by research funding from Wyeth Research, Cambridge, MA. NR 21 TC 220 Z9 231 U1 2 U2 17 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 MAR 10 PY 2010 VL 28 IS 8 BP 1301 EP 1307 DI 10.1200/JCO.2009.25.8707 PG 7 WC Oncology SC Oncology GA 565RP UT WOS:000275312300007 PM 20142587 ER PT J AU Rose, SL Krzyzanowska, MK Joffe, S AF Rose, Susannah L. Krzyzanowska, Monika K. Joffe, Steven TI Relationships Between Authorship Contributions and Authors' Industry Financial Ties Among Oncology Clinical Trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONFLICTS-OF-INTEREST; PHARMACEUTICAL-INDUSTRY; COMPETING INTERESTS; BIOMEDICAL-RESEARCH; SPONSORSHIP; ASSOCIATION; CONCLUSIONS; DISCLOSURE; DRUGS; METAANALYSES AB Purpose To test the hypothesis that authors who play key scientific roles in oncology clinical trials, and who therefore have increased influence over the design, analysis, interpretation or reporting of trials, are more likely than those who do not play such roles to have financial ties to industry. Methods Data were abstracted from all trials (n = 235) of drugs or biologic agents published in the Journal of Clinical Oncology between January 1, 2006 and June 30, 2007. Article-level data included sponsorship, age group (adult v pediatric), phase, single versus multicenter, country (United States v other), and number of authors. Author-level data (n = 2,927) included financial ties (eg, employment, consulting) and performance of key scientific roles (ie, conception/design, analysis/ interpretation, or manuscript writing). Associations between performance of key roles and financial ties, adjusting for article-level covariates, were examined using generalized linear mixed models. Results One thousand eight hundred eighty-one authors (64%) reported performing at least one key role, and 842 authors (29%) reported at least one financial tie. Authors who reported performing a key role were more likely than other authors to report financial ties to industry (adjusted odds ratio [OR], 4.3; 99% Cl, 3.0 to 6.0; P < .0001). The association was stronger among trials with, compared with those without, industry funding (OR, 5.0 [99% Cl, 3.4 to 7.5] v OR, 2.5 [99% Cl, 1.3 to 4.8]), but was present regardless of sponsorship. Conclusion Authors who perform key roles in the conception and design, analysis, and interpretation, or reporting of oncology clinical trials are more likely than authors who do not perform such roles to have financial ties to industry. C1 [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Dept Hlth Care Policy, Sch Med, Cambridge, MA 02138 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM steven_joffe@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 FU National Cancer Institute [2R25CA092203-08] FX Supported by National Cancer Institute Grant No. 2R25CA092203-08 (S. L. R.). NR 46 TC 19 Z9 19 U1 1 U2 6 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 MAR 10 PY 2010 VL 28 IS 8 BP 1316 EP 1321 DI 10.1200/JCO.2008.21.6606 PG 6 WC Oncology SC Oncology GA 565RP UT WOS:000275312300009 PM 20065190 ER PT J AU Manne, SL Meropol, NJ Weinberg, DS Vig, H Catts, ZAK Manning, C Ross, E Shannon, K Chung, DC AF Manne, Sharon L. Meropol, Neal J. Weinberg, David S. Vig, Hetal Catts, Zohra Ali-Khan Manning, Cheri Ross, Eric Shannon, Kristen Chung, Daniel C. TI Facilitating Informed Decisions Regarding Microsatellite Instability Testing Among High-Risk Individuals Diagnosed With Colorectal Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LYNCH-SYNDROME; REDUCING MORBIDITY; COLON-CANCER; WOMEN; AID; STRATEGIES; MORTALITY; KNOWLEDGE; ATTITUDES; MUTATION AB Purpose To evaluate the impact of a CD-ROM intervention in the education of patients with suspected Lynch syndrome (LS) about microsatellite instability (MSI) and immunohisochemistry (IHC) testing. Patients and Methods Two hundred thirteen patients meeting Bethesda criteria were randomly assigned to receive either a brief educational session with a health educator (n = 105) or a brief educational session plus a CD-ROM (n = 108). Assessments were administered at baseline and 2 weeks post-treatment. Primary outcomes included MSI and IHC knowledge and level of satisfaction with and completeness of the preparation to make the decision for MSI testing. Secondary outcomes included decisional conflict, difficulty making the decision, cancer-specific and global anxiety, and level of discussion about MSI testing with family and friends. Results Participants in the education plus CD-ROM condition reported significant increases in knowledge about the MSI and IHC tests, greater satisfaction with the preparation to make a decision for testing, lower decisional conflict, and greater decisional self-efficacy. The effects of the education plus CD-ROM on most outcomes were not moderated by preintervention levels of exposure to MSI testing, family support for MSI testing, or the family history of cancer. Conclusion Incorporation of new media education strategies for individuals at risk for LS may be a valuable component of the informed consent process. As clinical criteria for MSI and IHC testing continue to expand, the need for alternative educational approaches to meet this increased demand could be met by the self-administered computer-based strategy that we described. C1 [Manne, Sharon L.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Helen F Graham Canc Ctr Christiana Care, Newark, DE USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Triad Interact Inc, Washington, DC USA. RP Manne, SL (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave,P1100, Philadelphia, PA 19111 USA. EM Sharon.Manne@fccc.edu FU National Cancer Institute [CA109332]; Fox Chase Cancer Center [P30 CA006927] FX Supported by Grant No. CA109332 from the National Cancer Institute and Grant No. P30 CA006927 to Fox Chase Cancer Center. NR 28 TC 22 Z9 22 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2010 VL 28 IS 8 BP 1366 EP 1372 DI 10.1200/JCO.2009.25.0399 PG 7 WC Oncology SC Oncology GA 565RP UT WOS:000275312300016 PM 20142594 ER PT J AU Ghobrial, IM Gertz, M LaPlant, B Camoriano, J Hayman, S Lacy, M Chuma, S Harris, B Leduc, R Rourke, M Ansell, SM DeAngelo, D Dispenzieri, A Bergsagel, L Reeder, C Anderson, KC Richardson, PG Treon, SP Witzig, TE AF Ghobrial, Irene M. Gertz, Morie LaPlant, Betsy Camoriano, John Hayman, Suzanne Lacy, Martha Chuma, Stacey Harris, Brianna Leduc, Renee Rourke, Meghan Ansell, Stephen M. DeAngelo, Daniel Dispenzieri, Angela Bergsagel, Leif Reeder, Craig Anderson, Kenneth C. Richardson, Paul G. Treon, Steven P. Witzig, Thomas E. TI Phase II Trial of the Oral Mammalian Target of Rapamycin Inhibitor Everolimus in Relapsed or Refractory Waldenstrom Macroglobulinemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; SINGLE-AGENT TEMSIROLIMUS; RENAL-CELL CARCINOMA; RITUXIMAB THERAPY; MULTIPLE-MYELOMA; INTERFERON-ALPHA; CLINICAL-TRIALS; CANCER; PATHWAYS AB Purpose The phosphatidylinositol 3-kinase/mammalian target of rapamycin (mTOR) signal transduction pathway controls cell proliferation and survival. Everolimus is an oral agent targeting raptor mTOR (mTORC1). The trial's goal was to determine the antitumor activity and safety of single-agent everolimus in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM). Patients and Methods Eligible patients had measurable disease (immunoglobulin M monoclonal protein > 1,000 mg/dL with > 10% marrow involvement or nodal masses > 2 cm), a platelet count more than 75,000 x 10(6)/L, a neutrophil count more than 1,000 x 10(6)/L, and a creatinine and bilirubin less than 2 x the laboratory upper limit of normal. Patients received everolimus 10 mg orally daily and were evaluated monthly. Tumor response was assessed after cycles 2 and 6 and then every three cycles until progression. Results Fifty patients were treated. The median age was 63 years (range, 43 to 85 years). The overall response rate (complete response plus partial remission [PR] plus minimal response [MR]) was 70% (95% Cl, 55% to 82%), with a PR of 42% and 28% MR. The median duration of response and median progression-free survival (PFS) have not been reached. The estimated PFS at 6 and 12 months is 75% (95% Cl, 64% to 89%) and 62% (95% Cl, 48% to 80%), respectively. Grade 3 or higher related toxicities were observed in 56% of patients. The most common were hematologic toxicities with cytopenias. Pulmonary toxicity occurred in 10% of patients. Dose reductions due to toxicity occurred in 52% of patients. Conclusion Everolimus has high single-agent activity with an overall response rate of 70% and manageable toxicity in patients with relapsed WM and offers a potential new therapeutic strategy for this patient group. C1 [Witzig, Thomas E.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. Dana Farber Canc Ctr, Boston, MA USA. Mayo Fdn, Rochester, MN USA. Mayo Clin, Coll Med, Scottsdale, AZ USA. Mayo Fdn, Scottsdale, AZ USA. RP Witzig, TE (reprint author), Mayo Clin, Coll Med, Stabile 628,200 1st St SW, Rochester, MN 55905 USA. EM witzig@mayo.edu RI Bergsagel, Peter/A-7842-2011; OI Bergsagel, Peter/0000-0003-1523-7388; Harris, Brianna/0000-0001-6229-9907; Dispenzieri, Angela/0000-0001-8780-9512 FU Novartis Inc; International Waldenstrom's Macroglobulinemia Foundation; National Institutes of Health [R21CA126119] FX Supported in part by Novartis Inc, International Waldenstrom's Macroglobulinemia Foundation, and National Institutes of Health Grant No. R21CA126119. NR 48 TC 79 Z9 79 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2010 VL 28 IS 8 BP 1408 EP 1414 DI 10.1200/JCO.2009.24.0994 PG 7 WC Oncology SC Oncology GA 565RP UT WOS:000275312300022 PM 20142598 ER PT J AU Ghobrial, IM Hong, FX Padmanabhan, S Badros, A Rourke, M Leduc, R Chuma, S Kunsman, J Warren, D Harris, B Sam, A Anderson, KC Richardson, PG Treon, SP Weller, E Matous, J AF Ghobrial, Irene M. Hong, Fangxin Padmanabhan, Swaminathan Badros, Ashraf Rourke, Meghan Leduc, Renee Chuma, Stacey Kunsman, Janet Warren, Diane Harris, Brianna Sam, Amy Anderson, Kenneth C. Richardson, Paul G. Treon, Steven P. Weller, Edie Matous, Jeffrey TI Phase II Trial of Weekly Bortezomib in Combination With Rituximab in Relapsed or Relapsed and Refractory Waldenstrom Macroglobulinemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; COOPERATIVE-ONCOLOGY-GROUP; NF-KAPPA-B; CLINICAL-TRIAL; THERAPY; MANAGEMENT; SURVIVAL; MYELOMA; UPDATE AB Purpose This study aimed to determine activity and safety of weekly bortezomib and rituximab in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM). Patients and Methods Patients who had at least one previous therapy were eligible. All patients received bortezomib intravenously weekly at 1.6 mg/m(2) on days 1, 8, and 15, every 28 days for six cycles and rituximab 375 mg/m(2) weekly on cycles 1 and 4. The primary end point was the percentage of patients with at least a minor response. Results Thirty-seven patients were treated. The majority of patients (78%) completed treatment per protocol. At least minimal response (MR) or better was observed in 81% (95% Cl, 65% to 92%), with two patients (5%) in complete remission (CR)/near CR, 17 patients (46%) in partial response, and 11 patients (30%) in MR. The median time to progression was 16.4 months (95% Cl, 11.4 to 21.1 months). Death occurred in one patient due to viral pneumonia. The most common grade 3 and 4 therapy-related adverse events included reversible neutropenia in 16%, anemia in 11%, and thrombocytopenia in 14%. Grade 3 peripheral neuropathy occurred in only two patients (5%). The median progression-free (PFS) is 15.6 months (95% Cl, 11 to 21 months), with estimated 12-month and 18-month PFS of 57% (95% Cl, 39% to 75%) and 45% (95% Cl, 27% to 63%), respectively. The median overall survival has not been reached. Conclusion The combination of weekly bortezomib and rituximab showed significant activity and minimal neurologic toxicity in patients with relapsed WM. C1 [Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Canc Ctr, Buffalo, NY USA. Univ Maryland, Baltimore, MD 21201 USA. Rocky Mt Canc Ctr, Denver, CO USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu OI Harris, Brianna/0000-0001-6229-9907 FU International Waldenstrom Macroglobulinemia Foundation (IWMF); Michelle and Steven Kirsch lab for Waldenstrom Macroglobulinemia FX Supported in part by the International Waldenstrom Macroglobulinemia Foundation (IWMF), and Michelle and Steven Kirsch lab for Waldenstrom Macroglobulinemia. NR 32 TC 63 Z9 64 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2010 VL 28 IS 8 BP 1422 EP 1428 DI 10.1200/JCO.2009.25.3237 PG 7 WC Oncology SC Oncology GA 565RP UT WOS:000275312300024 PM 20142586 ER PT J AU Heinlen, LD McClain, MT Ritterhouse, LL Bruner, BF Edgerton, CC Keith, MP James, JA Harley, JB AF Heinlen, Latisha D. McClain, Micah T. Ritterhouse, Lauren L. Bruner, Benjamin F. Edgerton, Colin C. Keith, Michael P. James, Judith A. Harley, John B. TI 60 kD Ro and nRNP A Frequently Initiate Human Lupus Autoimmunity SO PLOS ONE LA English DT Article ID ANTI-SM ANTIBODIES; CLINICAL-SIGNIFICANCE; PEPTIDE IMMUNIZATION; HUMORAL AUTOIMMUNITY; SURFACE-STRUCTURES; REVISED CRITERIA; ERYTHEMATOSUS; AUTOANTIBODIES; DIAGNOSIS; NEPHRITIS AB Systemic lupus erythematosus (SLE) is a clinically heterogeneous, humoral autoimmune disorder. The unifying feature among SLE patients is the production of large quantities of autoantibodies. Serum samples from 129 patients collected before the onset of SLE and while in the United States military were evaluated for early pre-clinical serologic events. The first available positive serum sample frequently already contained multiple autoantibody specificities (65%). However, in 34 SLE patients the earliest pre-clinical serum sample positive for any detectable common autoantibody bound only a single autoantigen, most commonly 60 kD Ro (29%), nRNP A (24%), anti-phospholipids (18%) or rheumatoid factor (15%). We identified several recurrent patterns of autoantibody onset using these pre-diagnostic samples. In the serum samples available, anti-nRNP A appeared before or simultaneously with anti-nRNP 70 K in 96% of the patients who had both autoantibodies at diagnosis. Anti-60 kD Ro antibodies appeared before or simultaneously with anti-La (98%) or anti-52 kD Ro (95%). The autoantibody response in SLE patients begins simply, often binding a single specific autoantigen years before disease onset, followed by epitope spreading to additional autoantigenic specificities that are accrued in recurring patterns. C1 [Heinlen, Latisha D.; McClain, Micah T.; Ritterhouse, Lauren L.; Bruner, Benjamin F.; James, Judith A.] Oklahoma Med Res Fdn, Dept Clin Immunol, Oklahoma City, OK 73104 USA. [Heinlen, Latisha D.; Ritterhouse, Lauren L.; James, Judith A.; Harley, John B.] Univ Oklahoma, Hlth Sci Ctr, Dept Internal Med, Oklahoma City, OK USA. [Heinlen, Latisha D.; Ritterhouse, Lauren L.; James, Judith A.; Harley, John B.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. [Edgerton, Colin C.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Keith, Michael P.] Natl Naval Med Ctr, Bethesda, MD USA. [Harley, John B.] US Dept Vet Affairs, Oklahoma City, OK USA. [Harley, John B.] Oklahoma Med Res Fdn, Dept Arthrit & Immunol, Oklahoma City, OK 73104 USA. RP Heinlen, LD (reprint author), Oklahoma Med Res Fdn, Dept Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM harley@omrf.org FU National Institutes of Health [AI31584, AR48045, AR49084, AR45084, AR45451, RR15577, AR48940, RR20143, AI62629, AI50350]; Kirkland Scholar Awards; United States Department of Veterans Affairs; Lou Kerr Chair in Biomedical Research FX This work was supported in part by grants from the National Institutes of Health (AI31584, AR48045, AR49084, AR45084, AR45451, RR15577, AR48940, RR20143, AI62629, AI50350), Kirkland Scholar Awards (JBH and JAJ) and the United States Department of Veterans Affairs. This work was also supported in part by the Lou Kerr Chair in Biomedical Research to JAJ. Bio-Rad provided the ANA test kits and selected the laboratory as a beta-test site for their commercial bead based assay. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 22 Z9 22 U1 1 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 MAR 10 PY 2010 VL 5 IS 3 AR e9599 DI 10.1371/journal.pone.0009599 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 565XE UT WOS:000275328800012 PM 20224770 ER PT J AU Miranda, KC Karet, FE Brown, D AF Miranda, Kevin C. Karet, Fiona E. Brown, Dennis TI An Extended Nomenclature for Mammalian V-ATPase Subunit Genes and Splice Variants SO PLOS ONE LA English DT Article ID VACUOLAR H+-ATPASE; PROTON-TRANSLOCATING ATPASE; RENAL TUBULAR-ACIDOSIS; TISSUE-SPECIFIC ISOFORMS; MOLECULAR-CLONING; CHROMAFFIN GRANULES; LUMINAL ACIDIFICATION; MESSENGER-RNA; CDNA CLONING; C-SUBUNIT AB The vacuolar-type H(+)-ATPase (V-ATPase) is a multisubunit proton pump that is involved in both intra-and extracellular acidification processes throughout the body. Multiple homologs and splice variants of V-ATPase subunits are thought to explain its varied spatial and temporal expression pattern in different cell types. Recently subunit nomenclature was standardized with a total of 22 subunit variants identified. However this standardization did not accommodate the existence of splice variants and is therefore incomplete. Thus, we propose here an extension of subunit nomenclature along with a literature and sequence database scan for additional V-ATPase subunits. An additional 17 variants were pulled from a literature search while 4 uncharacterized potential subunit variants were found in sequence databases. These findings have been integrated with the current V-ATPase knowledge base to create a new V-ATPase subunit catalogue. It is envisioned this catalogue will form a new platform on which future studies into tissue-and organelle-specific V-ATPase expression, localization and function can be based. C1 [Miranda, Kevin C.; Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. [Miranda, Kevin C.; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Ctr Syst Biol, Boston, MA 02114 USA. [Miranda, Kevin C.; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Karet, Fiona E.] Univ Cambridge, Dept Med Genet, Cambridge, England. RP Miranda, KC (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. EM fek1000@cam.ac.uk; brown@receptor.mgh.harvard.edu OI Karet, Fiona/0000-0002-2457-2869 FU National Kidney Foundation; Wellcome Trust; National Institutes of Health [DK42956] FX KCM is funded through a National Kidney Foundation Research Fellowship. FEK is funded through the Wellcome Trust, while DB is funded by a National Institutes of Health grant DK42956 (DB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 20 Z9 21 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 MAR 10 PY 2010 VL 5 IS 3 AR e9531 DI 10.1371/journal.pone.0009531 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 565XE UT WOS:000275328800004 PM 20224822 ER PT J AU Xu, C Lo, A Yammanuru, A Tallarico, ASC Brady, K Murakami, A Barteneva, N Zhu, Q Marasco, WA AF Xu, Chen Lo, Agnes Yammanuru, Anuradha Tallarico, Aimee St. Clair Brady, Kristen Murakami, Akikazu Barteneva, Natasha Zhu, Quan Marasco, Wayne A. TI Unique Biological Properties of Catalytic Domain Directed Human Anti-CAIX Antibodies Discovered through Phage-Display Technology SO PLOS ONE LA English DT Article ID RENAL-CELL CARCINOMA; CARBONIC-ANHYDRASE-IX; DIAGNOSTIC BIOMARKER; IN-VITRO; CANCER; PROTEIN; THERAPY; IDENTIFICATION; EXPRESSION; KIDNEY AB Carbonic anhydrase IX (CAIX, gene G250/MN-encoded transmembrane protein) is highly expressed in various human epithelial tumors such as renal clear cell carcinoma (RCC), but absent from the corresponding normal tissues. Besides the CA signal transduction activity, CAIX may serve as a biomarker in early stages of oncogenesis and also as a reliable marker of hypoxia, which is associated with tumor resistance to chemotherapy and radiotherapy. Although results from preclinical and clinical studies have shown CAIX as a promising target for detection and therapy for RCC, only a limited number of murine monoclonal antibodies (mAbs) and one humanized mAb are available for clinical testing and development. In this study, paramagnetic proteoliposomes of CAIX (CAIX-PMPLs) were constructed and used for anti-CAIX antibody selection from our 27 billion human single-chain antibody (scFv) phage display libraries. A panel of thirteen human scFvs that specifically recognize CAIX expressed on cell surface was identified, epitope mapped primarily to the CA domain, and affinity-binding constants (KD) determined. These human anti-CAIX mAbs are diverse in their functions including induction of surface CAIX internalization into endosomes and inhibition of the carbonic anhydrase activity, the latter being a unique feature that has not been previously reported for anti-CAIX antibodies. These human anti-CAIX antibodies are important reagents for development of new immunotherapies and diagnostic tools for RCC treatment as well as extending our knowledge on the basic structure-function relationships of the CAIX molecule. C1 [Xu, Chen; Lo, Agnes; Yammanuru, Anuradha; Tallarico, Aimee St. Clair; Brady, Kristen; Murakami, Akikazu; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Barteneva, Natasha] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Barteneva, Natasha] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Xu, Chen; Lo, Agnes; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Barteneva, Natasha] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Xu, C (reprint author), Beijing Tri Prime Genet Engn Corp Ltd, Beijing, Peoples R China. EM quan_zhu@dfci.harvard.edu; wayne_marasco@dfci.harvard.edu FU National Institutes of Health (NIH) [R21DK072282, 1S10RR23459-01]; Kidney SPORE [5P50CA101942]; PI; National Foundation for Cancer Research; [R21AI058804] FX This study was supported by National Institutes of Health (NIH) grants R21DK072282 to WAM, in part by the Kidney SPORE grant 5P50CA101942 where WAM is a subcontract PI, and in part by R21AI058804 to QKZ. The Flow and Imaging Cytometry Resource (FICR) and Imagestream 100 instrument used in this study were funded, in part, under NIH grant 1S10RR23459-01. The FACS Calibur used for flow cytometric analysis performed in this study was funded through the National Foundation for Cancer Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 21 Z9 22 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 MAR 10 PY 2010 VL 5 IS 3 AR e9625 DI 10.1371/journal.pone.0009625 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 565XE UT WOS:000275328800020 PM 20224781 ER PT J AU Nautiyal, A Chaukiyal, P AF Nautiyal, Amit Chaukiyal, Pooja TI Second neoplasm: 31-year latency after childhood leukemia SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material ID CANCER SURVIVOR C1 [Nautiyal, Amit] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Chaukiyal, Pooja] Vet Affairs Pittsburgh Hlth Care Syst, Dept Med, Pittsburgh, PA USA. RP Nautiyal, A (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD MAR 9 PY 2010 VL 182 IS 4 BP E185 EP E185 DI 10.1503/cmaj.090562 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 560RO UT WOS:000274920000022 PM 20026628 ER PT J AU Shin, SH Hung, CL Uno, H Hassanein, AH Verma, A Bourgoun, M Kober, L Ghali, JK Velazquez, EJ Califf, RM Pfeffer, MA Solomon, SD AF Shin, Sung-Hee Hung, Chung-Lieh Uno, Hajime Hassanein, Amira H. Verma, Anil Bourgoun, Mikhail Kober, Lars Ghali, Jalal K. Velazquez, Eric J. Califf, Robert M. Pfeffer, Marc A. Solomon, Scott D. CA Valsartan Acute Myocardial Infarct TI Mechanical Dyssynchrony After Myocardial Infarction in Patients With Left Ventricular Dysfunction, Heart Failure, or Both SO CIRCULATION LA English DT Article DE echocardiography; heart failure; myocardial infarction ID CARDIAC-RESYNCHRONIZATION THERAPY; ECHOCARDIOGRAPHIC METHOD; MITRAL REGURGITATION; PREDICT RESPONSE; QRS DURATION; STRAIN; TISSUE; VALIDATION; ASYNCHRONY; VALSARTAN AB Background-Mechanical dyssynchrony is considered an independent predictor for adverse cardiovascular outcomes in patients with heart failure. However, its importance as a risk factor after myocardial infarction is not well defined. Methods and Results-We examined the influence of mechanical dyssynchrony on outcome in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiography study. B-mode speckle tracking with velocity vector imaging was used to assess ventricular synchrony in 381 patients who had image quality sufficient for analysis. Time to regional peak velocity and time to strain rate were measured among 12 left ventricular segments from the apical 4- and 2- chamber views, and the SDs between all 12 segments were used as a measure of dyssynchrony. The relationships between the SD of time to regional peak velocity and strain rate and clinical outcome of death or heart failure were assessed. In a multivariate Cox model adjusted for clinical and echocardiographic variables, the SD of time to peak velocity (hazard ratio per 10 ms, 1.10; 95% confidence interval, 1.02 to 1.18; P=0.010) and the SD of time to strain rate (hazard ratio per 10 ms, 1.16; 95% confidence interval, 1.06 to 1.27; P=0.001) were independent predictors of death or heart failure. Conclusion-Left ventricular dyssynchrony is independently associated with increased risk of death or heart failure after myocardial infarction, suggesting that contractile pattern may play a role in post-myocardial infarction prognosis. (Circulation. 2010; 121: 1096-1103.) C1 [Shin, Sung-Hee; Hung, Chung-Lieh; Hassanein, Amira H.; Verma, Anil; Bourgoun, Mikhail; Pfeffer, Marc A.; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Uno, Hajime] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Uno, Hajime] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kober, Lars] Univ Copenhagen, Copenhagen, Denmark. [Ghali, Jalal K.] Wayne State Med Ctr, Detroit, MI USA. [Velazquez, Eric J.; Califf, Robert M.] Duke Univ, Med Ctr, Durham, NC USA. RP Solomon, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM ssolomon@rics.bwh.harvard.edu RI Max, Mad/E-5238-2010; Solomon, Scott/I-5789-2013 OI Max, Mad/0000-0001-6966-6829; FU Novartis Pharmaceuticals, East Hanover, NJ FX VALIANT was supported by a grant from Novartis Pharmaceuticals, East Hanover, NJ. NR 42 TC 54 Z9 58 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 MAR 9 PY 2010 VL 121 IS 9 BP 1096 EP 1103 DI 10.1161/CIRCULATIONAHA.109.863795 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 565XR UT WOS:000275331600006 PM 20176989 ER PT J AU Truong, QA Yared, K Maurovich-Horvat, P Siegel, E Cubeddu, RJ King, ME Heist, EK Mansour, M Holmvang, G AF Truong, Quynh A. Yared, Kibar Maurovich-Horvat, Pal Siegel, Emily Cubeddu, Roberto J. King, Mary Etta Heist, E. Kevin Mansour, Moussa Holmvang, Godtfred TI Double-Chambered Right Ventricle and Situs Inversus With Dextrocardia SO CIRCULATION LA English DT Editorial Material C1 [Truong, Quynh A.; Maurovich-Horvat, Pal; Siegel, Emily; Holmvang, Godtfred] Harvard Univ, Cardiac MR PET CT Program, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Truong, Quynh A.; Yared, Kibar; Cubeddu, Roberto J.; King, Mary Etta; Heist, E. Kevin; Mansour, Moussa; Holmvang, Godtfred] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Truong, Quynh A.; Maurovich-Horvat, Pal; Siegel, Emily; Holmvang, Godtfred] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Holmvang, G (reprint author), Harvard Univ, Cardiac MR PET CT Program, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,BUL 161, Boston, MA 02114 USA. EM gholmvang@partners.org OI Maurovich-Horvat, Pal/0000-0003-0885-736X FU NHLBI NIH HHS [K23 HL098370, L30 HL093806, L30 HL093806-01, T32 HL076136] NR 6 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 9 PY 2010 VL 121 IS 9 BP E229 EP E232 DI 10.1161/CIR.0b013e3181d56ebd PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 565XR UT WOS:000275331600014 PM 20212287 ER PT J AU Huang, HC Benoist, C Mathis, D AF Huang, Haochu Benoist, Christophe Mathis, Diane TI Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; B cell depletion therapy; CD20; plasma cell; autoantibody ID MONOCLONAL-ANTIBODIES; DIRECTED THERAPIES; AUTOIMMUNE-DISEASE; B-CELLS; MICE; EXPRESSION; DIFFERENTIATION; IMMUNOTHERAPY; ACTIVATION; SURVIVAL AB There is increasing appreciation of the important role of B cells in many autoimmune diseases and consequently, increasing interest in treating these disorders through B cell-depletion therapy with rituximab, an anti-CD20 monoclonal antibody. Yet, precisely how this and related drugs exert their therapeutic effects remains controversial. In particular, it is unclear how, in a number of contexts, rituximab can greatly reduce the titer of serum autoantibodies without substantially altering the overall antibody titer. We have studied the action of this drug in the K/BxN mouse model of inflammatory arthritis after first crossing in a human CD20 transgene. Rituximab treatment of these mice led to a decrease in the titer of serum antibodies targeting glucose-6-phosphate isomerase, the relevant autoantigen, but not in the total antibody titer. Glucose-6-phosphate isomerase-specific plasma cells did not reside primarily in the bone marrow as expected but rather in the spleen and lymph nodes, where they had short lives, expressed CD20, and were rapidly depleted by rituximab. These data support a model whereby autoreactive plasma cells (at least certain specificities thereof) are intrinsically different from protective antimicrobial plasma cells in their differentiation, migration, and survival properties. Rituximab targets the former and spares the latter. C1 [Huang, Haochu; Benoist, Christophe; Mathis, Diane] Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. [Huang, Haochu] Univ Chicago, Dept Med, Rheumatol Sect, Chicago, IL 60637 USA. [Huang, Haochu] Univ Chicago, Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA. [Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. RP Huang, HC (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM hhuang@bsd.uchicago.edu; cbdm@hms.harvard.edu FU National Institutes of Health [R01 AR046580]; Joslin's National Institute of Diabetes and Digestive and Kidney Diseases; Damon Runyon Cancer Research Foundation [DRG-1616] FX We thank Dr. Rudolf A. Manz for advice on plasma-cell detection, Vanesa Tran, Kimie Hattori, and Adriana Ortiz-Lopez for help with mice, Genentech for providing human CD20 transgenic mice and rituximab, Marilyn Kehry and Robert Dunn for anti-mouse CD20 mAb, and Dr. Martin Weigert for critical reading of the manuscript. This work was supported by Grant R01 AR046580 (to D. M. and C. B.) from the National Institutes of Health and by grants from Joslin's National Institute of Diabetes and Digestive and Kidney Diseases-supported Diabetes and Endocrinology Research Center cores. H. H. was supported by Grant DRG-1616 from the Damon Runyon Cancer Research Foundation. NR 24 TC 61 Z9 63 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 9 PY 2010 VL 107 IS 10 BP 4658 EP 4663 DI 10.1073/pnas.1001074107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 566KF UT WOS:000275368400032 PM 20176942 ER PT J AU Horak, P Crawford, AR Vadysirisack, DD Nash, ZM DeYoung, MP Sgroi, D Ellisen, LW AF Horak, Peter Crawford, Andrew R. Vadysirisack, Douangsone D. Nash, Zachary M. DeYoung, M. Phillip Sgroi, Dennis Ellisen, Leif W. TI Negative feedback control of HIF-1 through REDD1-regulated ROS suppresses tumorigenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hypoxia; mTOR; mitochondria; breast cancer; tuberous sclerosis ID EXPRESSION PROFILES; HUMAN CANCER; CELL-GROWTH; HYPOXIA; MTOR; GENE; REDD1; APOPTOSIS; INHIBITION; ADAPTATION AB The HIF family of hypoxia-inducible transcription factors are key mediators of the physiologic response to hypoxia, whose dysregulation promotes tumorigenesis. One important HIF-1 effector is the REDD1 protein, which is induced by HIF-1 and which functions as an essential regulator of TOR complex 1 (TORC1) activity in Drosophila and mammalian cells. Here we demonstrate a negative feedback loop for regulation of HIF-1 by REDD1, which plays a key role in tumor suppression. Genetic loss of REDD1 dramatically increases HIF-1 levels and HIF-regulated target gene expression in vitro and confers tumorigenicity in vivo. Increased HIF-1 in REDD1(-/-) ells induces a shift to glycolytic metabolism and provides a growth advantage under hypoxic conditions, and HIF-1 knockdown abrogates this advantage and suppresses tumorigenesis. Surprisingly, however, HIF-1 up-regulation in REDD1(-/-) cells is largely independent of mTORC1 activity. Instead, loss of REDD1 induces HIF-1 stabilization and tumorigenesis through a reactive oxygen species (ROS) -dependent mechanism. REDD1(-/-) cells demonstrate a substantial elevation of mitochondrial ROS, and antioxidant treatment is sufficient to normalize HIF-1 levels and inhibit REDD1-dependent tumor formation. REDD1 likely functions as a direct regulator of mitochondrial metabolism, as endogenous REDD1 localizes to the mitochondria, and this localization is required for REDD1 to reduce ROS production. Finally, human primary breast cancers that have silenced REDD1 exhibit evidence of HIF activation. Together, these findings uncover a specific genetic mechanism for HIF induction through loss of REDD1. Furthermore, they de. ne REDD1 as a key metabolic regulator that suppresses tumorigenesis through distinct effects on mTORC1 activity and mitochondrial function. C1 [Horak, Peter; Crawford, Andrew R.; Vadysirisack, Douangsone D.; Nash, Zachary M.; DeYoung, M. Phillip; Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Horak, Peter; Crawford, Andrew R.; Vadysirisack, Douangsone D.; Nash, Zachary M.; DeYoung, M. Phillip; Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sgroi, Dennis] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu FU Austrian Science Fund (FWF); [R01 CA122589] FX We thank Nabeel Bardeesy and Raul Mostaslavsky for critical review of the manuscript. This work was supported by R01 CA122589 to L. W. E. and by an Austrian Science Fund (FWF) award to P. H. NR 34 TC 73 Z9 74 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 9 PY 2010 VL 107 IS 10 BP 4675 EP 4680 DI 10.1073/pnas.0907705107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 566KF UT WOS:000275368400035 PM 20176937 ER PT J AU Patel, GH Shulman, GL Baker, JT Akbudak, E Snyder, AZ Snyder, LH Corbetta, M AF Patel, Gaurav H. Shulman, Gordon L. Baker, Justin T. Akbudak, Erbil Snyder, Abraham Z. Snyder, Lawrence H. Corbetta, Maurizio TI Topographic organization of macaque area LIP SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BOLD signal; functional MRI; retinotopy; parietal cortex; visual attention ID POSTERIOR PARIETAL CORTEX; LATERAL INTRAPARIETAL AREA; FRONTAL EYE FIELDS; FUNCTIONAL ARCHITECTURE; BEHAVING MONKEY; CORTICOCORTICAL CONNECTIONS; ASSOCIATION CORTEX; VISUAL TOPOGRAPHY; SPATIAL ATTENTION; CEREBRAL-CORTEX AB Despite several attempts to define retinotopic maps in the macaque lateral intraparietal area (LIP) using histological, electrophysiological, and neuroimaging methods, the degree to which this area is topographically organized remains controversial. We recorded blood oxygenation level-dependent signals with functional MRI from two macaques performing a difficult visual search task on stimuli presented at the fovea or in the periphery of the visual field. The results revealed the presence of a single topographic representation of the contralateral hemifield in the ventral subdivision of the LIP (LIPv) in both hemispheres of both monkeys. Also, a foveal representation was localized in rostral LIPv rather than in dorsal LIP (LIPd) as previous experiments had suggested. Finally, both LIPd and LIPv responded only to contralateral stimuli. In contrast, human studies have reported multiple topographic maps in intraparietal cortex and robust responses to ipsilateral stimuli. These blood oxygenation level-dependent functional MRI results provide clear evidence for the topographic organization of macaque LIP that complements the results of previous electrophysiology studies, and also reveal some unexpected characteristics of this organization that have eluded these previous studies. The results also delineate organizational differences between LIPv and LIPd, providing support for these two histologically defined areas may subserve different visuospatial functions. Finally, these findings point to potential evolutionary differences in functional organization with human posterior parietal cortex. C1 [Patel, Gaurav H.; Akbudak, Erbil; Snyder, Abraham Z.; Corbetta, Maurizio] Washington Univ, Dept Radiol, St Louis, MO 63110 USA. [Patel, Gaurav H.; Shulman, Gordon L.; Snyder, Abraham Z.; Corbetta, Maurizio] Washington Univ, Dept Neurol, St Louis, MO 63110 USA. [Patel, Gaurav H.; Baker, Justin T.; Snyder, Lawrence H.; Corbetta, Maurizio] Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Patel, Gaurav H.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA. [Baker, Justin T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Patel, GH (reprint author), Washington Univ, Dept Radiol, St Louis, MO 63110 USA. EM gauravpatel@gmail.com RI Snyder, Lawrence/A-4593-2017 FU McDonnell Center for Systems Neuroscience at Washington University; National Institute of Neurological Disease and Stroke [R01 NS48013, F31 NS051972]; National Institute of Mental Health (NIMH) [R01 MH71920-06]; European Union [MEXC-CT-2004-006783]; National Eye Institute [R01 EY012135]; Washington University Silvio Conte Center (NIMH) [MH-071616]; National Science Foundation [0548890] FX We thank Tom Malone, David Borton, Marcel Fremont, Jason Vytlacil, Matt Reiter, Erin Reid, Chad Sylvester, Anthony Jack, Giovanni D'Avossa, Carlo Sestieri, Mark McAvoy, Justin Vincent, John Harwell, Donna Dierker, David Van Essen, Marc Raichle, Steve Petersen, Leonardo Chelazzi, and Wim Vanduffel for aiding this study and for their comments on the manuscript. This study was supported by the McDonnell Center for Systems Neuroscience at Washington University, National Institute of Neurological Disease and Stroke Grants R01 NS48013 and F31 NS051972, National Institute of Mental Health (NIMH) Grant R01 MH71920-06, a European Union-funded Marie Curie Chair (MEXC-CT-2004-006783), National Eye Institute Grant R01 EY012135, the Washington University Silvio Conte Center (NIMH Grant MH-071616), and National Science Foundation (Integrative Graduate Education and Research Traineeship Program Grant 0548890). NR 50 TC 29 Z9 29 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 9 PY 2010 VL 107 IS 10 BP 4728 EP 4733 DI 10.1073/pnas.0908092107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 566KF UT WOS:000275368400044 PM 20173093 ER PT J AU Bouche, C Lopez, X Fleischman, A Cypess, AM O'Shea, S Stefanovski, D Bergman, RN Rogatsky, E Stein, DT Kahn, CR Kulkarni, RN Goldfine, AB AF Bouche, Clara Lopez, Ximena Fleischman, Amy Cypess, Aaron M. O'Shea, Sheila Stefanovski, Darko Bergman, Richard N. Rogatsky, Eduard Stein, Daniel T. Kahn, C. Ronald Kulkarni, Rohit N. Goldfine, Allison B. TI Insulin enhances glucose-stimulated insulin secretion in healthy humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE beta cell; type 2 diabetes mellitus; insulin resistance; insulin clearance; C-peptide ID PANCREATIC BETA-CELLS; DEPENDENT DIABETES-MELLITUS; C-PEPTIDE; GENE-EXPRESSION; HUMAN ISLETS; RECEPTOR SUBSTRATE-1; CONNECTING PEPTIDE; MICE; HYPERINSULINEMIA; HYPERGLYCEMIA AB Islet beta-cells express both insulin receptors and insulin-signaling proteins. Recent evidence from rodents in vivo and from islets isolated from rodents or humans suggests that the insulin signaling pathway is physiologically important for glucose sensing. We evaluated whether insulin regulates beta-cell function in healthy humans in vivo. Glucose-induced insulin secretion was assessed in healthy humans following 4-h saline (low insulin/sham clamp) or isoglycemic-hyperinsulinemic (high insulin) clamps using B28-Asp insulin that could be immunologically distinguished from endogenous insulin. Insulin and C-peptide clearance were evaluated to understand the impact of hyperinsulinemia on estimates of beta-cell function. Preexposure to exogenous insulin increased the endogenous insulin secretory response to glucose by approximate to 40%. C-peptide response also increased, although not to the level predicted by insulin. Insulin clearance was not saturated at hyperinsulinemia, but metabolic clearance of C-peptide, assessed by infusion of stable isotope-labeled C-peptide, increased modestly during hyperinsulinemic clamp. These studies demonstrate that insulin potentiates glucose-stimulated insulin secretion in vivo in healthy humans. In addition, hyperinsulinemia increases C-peptide clearance, which may lead to modest underestimation of beta-cell secretory response when using these methods during prolonged dynamic testing. C1 [Bouche, Clara; Lopez, Ximena; Fleischman, Amy; Cypess, Aaron M.; O'Shea, Sheila; Kahn, C. Ronald; Kulkarni, Rohit N.; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Bouche, Clara; Lopez, Ximena; Fleischman, Amy; Cypess, Aaron M.; Kahn, C. Ronald; Kulkarni, Rohit N.; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lopez, Ximena] Massachusettes Gen Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Fleischman, Amy] Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Stefanovski, Darko; Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Rogatsky, Eduard; Stein, Daniel T.] Albert Einstein Coll Med, Div Endocrinol Diabet & Metab, Dept Med, Bronx, NY 10461 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu; allison.goldfine@joslin.harvard.edu FU National Institutes of Health [K23-DK02795, R01 DK070648, DK67536, DK061644, DK33201, P30-DK36836, M01-RR001032, RR12248]; American Diabetes Association [06-CD-07]; Harvard 50th Anniversary Scholars in Medicine; Priscilla White Fellowship; Lilly Fellowship; Harvard Massachusetts Institute of Technology Health Sciences and Technology-Beth Israel Deaconess Medical Center FX Supported by National Institutes of Health Grants K23-DK02795, R01 DK070648, DK67536, DK061644, DK33201, P30-DK36836, M01-RR001032, and RR12248; American Diabetes Association 06-CD-07; the Harvard 50th Anniversary Scholars in Medicine: Priscilla White Fellowship; a Lilly Fellowship Grant; and the Clinical Investigator Training Program of Harvard Massachusetts Institute of Technology Health Sciences and Technology-Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc. and Merck & Company, Inc. NR 46 TC 44 Z9 48 U1 2 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 MAR 9 PY 2010 VL 107 IS 10 BP 4770 EP 4775 DI 10.1073/pnas.1000002107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 566KF UT WOS:000275368400051 PM 20176932 ER PT J AU Sykiotis, GP Bohmann, D AF Sykiotis, Gerasimos P. Bohmann, Dirk TI Stress-Activated Cap'n'collar Transcription Factors in Aging and Human Disease SO SCIENCE SIGNALING LA English DT Review ID ANTIOXIDANT-RESPONSE ELEMENT; AMYOTROPHIC-LATERAL-SCLEROSIS; SMALL MAF PROTEINS; OBSTRUCTIVE PULMONARY-DISEASE; HEME OXYGENASE-1 GENE; NAD(P)H-QUINONE OXIDOREDUCTASE1 GENE; AFLATOXIN-INDUCED TUMORIGENESIS; NRF2 ENHANCES SUSCEPTIBILITY; GLUTATHIONE S-TRANSFERASES; FACTOR E2-RELATED FACTOR-2 AB Cap'n'collar (Cnc) transcription factors are conserved in metazoans and have important developmental and homeostatic functions. The vertebrate Nrf1, Nrf2, and Nrf3; the Caenorhabditis elegans SKN-1; and the Drosophila CncC comprise a subgroup of Cnc factors that mediate adaptive responses to cellular stress. The most studied stress-activated Cnc factor is Nrf2, which orchestrates the transcriptional response of cells to oxidative stressors and electrophilic xenobiotics. In rodent models, signaling by Nrf2 defends against oxidative stress and aging-associated disorders, such as neurodegeneration, respiratory diseases, and cancer. In humans, polymorphisms that decrease Nrf2 abundance have been associated with various pathologies of the skin, respiratory system, and digestive tract. In addition to preventing disease in rodents and humans, Cnc factors have life-span-extending and anti-aging functions in invertebrates. However, despite the pro-longevity and antioxidant roles of stress-activated Cnc factors, their activity paradoxically declines in aging model organisms and in humans suffering from progressive respiratory disease or neurodegeneration. We review the roles and regulation of stress-activated Cnc factors across species, present all reported instances in which their activity is paradoxically decreased in aging and disease, and discuss the possibility that the pharmacological restoration of Nrf2 signaling may be useful in the prevention and treatment of age-related diseases. C1 [Sykiotis, Gerasimos P.; Bohmann, Dirk] Univ Rochester, Med Ctr, Dept Biomed Genet, Rochester, NY 14642 USA. [Sykiotis, Gerasimos P.] Massachusetts Gen Hosp, Dept Internal Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Sykiotis, Gerasimos P.] Massachusetts Gen Hosp, Dept Internal Med, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. RP Sykiotis, GP (reprint author), Univ Rochester, Med Ctr, Dept Biomed Genet, Rochester, NY 14642 USA. EM gerasimos_sykiotis@urmc.rochester.edu OI Sykiotis, Gerasimos/0000-0002-9565-4941 FU NIH [RO3 CA123591] FX Support was provided by JP Wilmot Cancer Research Fellowship (G. P. S.) and NIH grant RO3 CA123591 (D. B). NR 321 TC 224 Z9 230 U1 2 U2 26 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 MAR 9 PY 2010 VL 3 IS 112 AR re3 DI 10.1126/scisignal.3112re3 PG 22 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 570CF UT WOS:000275648500003 PM 20215646 ER PT J AU Chen, J Krumholz, HM Wang, Y Curtis, JP Rathore, SS Ross, JS Normand, SLT Schreiner, GC Mulvey, G Nallamothu, BK AF Chen, Jersey Krumholz, Harlan M. Wang, Yun Curtis, Jeptha P. Rathore, Saif S. Ross, Joseph S. Normand, Sharon-Lise T. Schreiner, Geoffrey C. Mulvey, Gregory Nallamothu, Brahmajee K. TI Differences in Patient Survival After Acute Myocardial Infarction by Hospital Capability of Performing Percutaneous Coronary Intervention SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID SITE CARDIAC-CATHETERIZATION; PRIMARY ANGIOPLASTY; OUTCOMES; CARE; REGIONALIZATION; FACILITIES; THROMBOLYSIS; CENTERS; IMPACT; TRIAL AB Background: There are increasing calls for regionalization of acute myocardial infarction ( AMI) care in the United States to hospitals with the capacity to perform percutaneous coronary intervention (PCI). Whether regionalization will improve outcomes depends in part on the magnitude of existing differences in outcomes between PCI and non-PCI hospitals within the same health care region. Methods: A 100% sample of claims from Medicare fee-for-service beneficiaries 65 years or older hospitalized for AMI between January 1, 2004, and December 31, 2006, was used to calculate hospital-level, 30-day risk-standardized mortality rates (RSMRs). The RSMRs between PCI and local non-PCI hospitals were compared within local health care regions defined by hospital referral regions (HRRs). Results: A total of 523 119 AMI patients was admitted to 1382 PCI hospitals, and 194 909 AMI patients were admitted to 2491 non-PCI hospitals in 295 HRRs with at least 1 PCI and 1 non-PCI hospital. Although PCI hospitals had lower RSMRs than non-PCI hospitals ( mean, 16.1% vs 16.9%; P < .001), considerable overlap was seen in RSMRs between non-PCI and PCI hospitals within the same HRR. In 80 HRRs, the RSMRs at the best-performing PCI hospital were lower than those at local non-PCI hospitals by 3% or more. Among the remaining HRRs, the RSMRs at the best-performing PCI hospital were lower by 1.5% to 3.0% in 104 HRRs and by greater than 0 to 1.5% in 74 HRRs. In 37 HRRs, the RSMRs at the best-performing PCI hospital were no better or were higher than at local non-PCI hospitals. Conclusions: The magnitude of benefit from comprehensively regionalizing AMI care to PCI hospitals appears to vary greatly across HRRs. These findings support a tailored regionalization policy that targets areas with the greatest outcome differences between PCI and local non-PCI hospitals. C1 [Chen, Jersey] Yale Univ, Sch Med, Dept Internal Med, Cardiol Sect,Div Cardiol, New Haven, CT 06520 USA. [Chen, Jersey; Krumholz, Harlan M.; Wang, Yun; Curtis, Jeptha P.; Schreiner, Geoffrey C.; Mulvey, Gregory] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Ross, Joseph S.] Mt Sinai Sch Med, Div Geriatr & Palliat Med, New York, NY USA. [Ross, Joseph S.] James P Peters Vet Adm Med Ctr, Hlth Serv Res & Dev Res Enhancement Program, Bronx, NY USA. [Ross, Joseph S.] James P Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Nallamothu, Brahmajee K.] Univ Michigan, Vet Affairs Ann Arbor Hlth Serv Res & Dev Ctr Exc, Ann Arbor, MI USA. [Nallamothu, Brahmajee K.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. RP Chen, J (reprint author), Yale Univ, Sch Med, Dept Internal Med, Cardiol Sect,Div Cardiol, 333 Cedar St,POB 208017, New Haven, CT 06520 USA. EM jersey.chen@yale.edu FU NIA NIH HHS [K08 AG032886-02, K08 AG032886] NR 20 TC 12 Z9 12 U1 0 U2 1 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 MAR 8 PY 2010 VL 170 IS 5 BP 433 EP 439 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 565PU UT WOS:000275307300007 PM 20212179 ER PT J AU Stevens, JC Chia, R Hendriks, WT Bros-Facer, V van Minnen, J Martin, JE Jackson, GS Greensmith, L Schiavo, G Fisher, EMC AF Stevens, James C. Chia, Ruth Hendriks, William T. Bros-Facer, Virginie van Minnen, Jan Martin, Joanne E. Jackson, Graham S. Greensmith, Linda Schiavo, Giampietro Fisher, Elizabeth M. C. TI Modification of Superoxide Dismutase 1 (SOD1) Properties by a GFP Tag - Implications for Research into Amyotrophic Lateral Sclerosis (ALS) SO PLOS ONE LA English DT Article ID FAMILIAL ALS; MUTANT SOD1; HUMAN-CELLS; MUTATIONS; PROTEIN; ULTRACENTRIFUGATION; DEATH; MODEL; GENE; MICE AB Background: Since the discovery that mutations in the enzyme SOD1 are causative in human amyotrophic lateral sclerosis (ALS), many strategies have been employed to elucidate the toxic properties of this ubiquitously expressed mutant protein, including the generation of GFP-SOD1 chimaeric proteins for studies in protein localization by direct visualization using fluorescence microscopy. However, little is known about the biochemical and physical properties of these chimaeric proteins, and whether they behave similarly to their untagged SOD1 counterparts. Methodology/Principal Findings: Here we compare the physicochemical properties of SOD1 and the effects of GFP-tagging on its intracellular behaviour. Immunostaining demonstrated that SOD1 alone and GFP-SOD1 have an indistinguishable intracellular distribution in PC12 cells. Cultured primary motor neurons expressing GFP or GFP-SOD1 showed identical patterns of cytoplasmic expression and of movement within the axon. However, GFP tagging of SOD1 was found to alter some of the intrinsic properties of SOD1, including stability and specific activity. Evaluation of wildtype and mutant SOD1, tagged at either the N- or C-terminus with GFP, in PC12 cells demonstrated that some chimaeric proteins were degraded to the individual proteins, SOD1 and GFP. Conclusions/Significance: Our findings indicate that most, but not all, properties of SOD1 remain the same with a GFP tag. C1 [Stevens, James C.; Chia, Ruth; Fisher, Elizabeth M. C.] UCL Inst Neurol, Dept Neurodegenerat Dis, London, England. [Hendriks, William T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. [Bros-Facer, Virginie; Greensmith, Linda] UCL Inst Neurol, Sobell Dept Motor Sci & Movement Disorders, London, England. [van Minnen, Jan] Univ Calgary, Hotchkiss Brain Inst, Dept Cell Biol & Anat, Calgary, AB, Canada. [Martin, Joanne E.] Queen Mary Univ London, ICMS Pathol Grp, London, England. [Jackson, Graham S.] UCL Inst Neurol, MRC Prion Unit, London, England. [Schiavo, Giampietro] Canc Res UK, Mol Neuropathobiol Lab, London, England. RP Stevens, JC (reprint author), UCL Inst Neurol, Dept Neurodegenerat Dis, London, England. EM e.fisher@prion.ucl.ac.uk OI Jackson, Graham/0000-0002-3125-2011; Schiavo, Giampietro/0000-0002-4319-8745 FU Ipsen Fund; UK Motor Neurone Disease Association; Research Advisory Board of St Bartholomew's and the Royal London Charitable Foundation [RAB04/F7]; Brain Research Trust; Biotechnology and Biological Sciences Research Council; Cancer Research UK; EU FP6 NEST [12702] FX This work was supported by research grants from The Ipsen Fund, the UK Motor Neurone Disease Association, the Research Advisory Board of St Bartholomew's and the Royal London Charitable Foundation (RAB04/F7), The Brain Research Trust, the Biotechnology and Biological Sciences Research Council, Cancer Research UK and EU FP6 NEST grant 12702. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 16 Z9 17 U1 1 U2 8 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 MAR 8 PY 2010 VL 5 IS 3 BP A8 EP A17 AR e9541 DI 10.1371/journal.pone.0009541 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 565WZ UT WOS:000275328200001 PM 20221404 ER PT J AU Tucker, JD Yang, LG Zhu, ZJ Yang, B Yin, YP Cohen, MS Chen, XS AF Tucker, Joseph D. Yang, Li-Gang Zhu, Zheng-Jun Yang, Bin Yin, Yue-Pin Cohen, Myron S. Chen, Xiang-Sheng TI Integrated syphilis/HIV screening in China: a qualitative analysis SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID STD SERVICES; HEALTH; PRIVATIZATION; PHYSICIANS; PROVIDERS; SETTINGS; SYSTEM; HIV-1; INDIA AB Background: The last decade has seen enormous advances in HIV treatment and care, but how to implement scaled up HIV testing, prevention, and treatment in low-income areas still presents a formidable public health challenge. South China faces expanding syphilis and sexually transmitted HIV epidemics, but health systems characteristics important for scaling up syphilis and HIV testing have not been defined. Methods: A purposive sample to ensure public, private, and public-private hybrid STI clinic inclusion was selected in a South China city. Eight key informant interviews were conducted with the STI clinic manager, followed by eight focus group discussions with physicians. Data collection relied on a semi-structured format that included questions in each of the following domains: 1) clinical facilities; 2) laboratory capacity with a focus on syphilis/HIV diagnosis; 3) clinic personnel; 4) physical space with a focus on locations to disclose confidential results; 5) financial support. Results: Public STI clinics had free syphilis testing/treatment and laboratory facilities to perform essential syphilis and HIV tests. However, despite serving a large number of STI patients, private STI clinics lacked nontreponemal syphilis testing, HIV testing, and had fewer connections to the public health infrastructure. Formally trained assistant physicians were 2.5 times as common as physicians at STI clinics. Only one of the 8 sites had onsite voluntary counseling and testing (VCT) services available. Conclusion: These STI case studies reveal the potential for expanding integrated syphilis/HIV services at public STI clinics in China. More health services research is needed to guide scale-up of syphilis/HIV testing in China. C1 [Tucker, Joseph D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Yang, Li-Gang; Yang, Bin] Guangdong Prov Ctr STI Control & Prevent, Guangzhou, Guangdong, Peoples R China. [Zhu, Zheng-Jun] Jiangmen Skin Hosp, Jiangmen, Peoples R China. [Yin, Yue-Pin; Chen, Xiang-Sheng] Natl Ctr STD Control, Nanjing, Peoples R China. [Cohen, Myron S.] UNC, Inst Global Hlth & Infect Dis, Chapel Hill Sch Med, Chapel Hill, NC USA. RP Tucker, JD (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM jtucker4@partners.org FU China Syphilis Working Group; UNC Fogarty AIDS International Research and Training Program (NIH FIC) [D43 TW01039]; UNC Social Science Research on HIV/AIDS in China (NIH NICHD) [R24 HD056670-01]; WHO Rapid Syphilis Test Project (WHO) [OD/TS-08-00088]; American Society for Tropical Medicine and Hygiene Postdoctoral Fellowship; Harvard Initiative for Global Health; US NIH Fogarty Institute FX We acknowledge the China Syphilis Working Group, the UNC Fogarty AIDS International Research and Training Program (NIH FIC D43 TW01039), the UNC Social Science Research on HIV/AIDS in China (NIH NICHD R24 HD056670-01), the WHO Rapid Syphilis Test Project (WHO OD/TS-08-00088), the American Society for Tropical Medicine and Hygiene Postdoctoral Fellowship, the Harvard Initiative for Global Health, and the US NIH Fogarty Institute. The authors would like to thank the assistance of Lu He-Kun, Zhang Bao-Yuan, Huang Shu-Jie, Deng Wei-Jun, Shen Song-Ying, and Wang Cheng. NR 31 TC 15 Z9 15 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD MAR 7 PY 2010 VL 10 AR 58 DI 10.1186/1472-6963-10-58 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 569TS UT WOS:000275625400001 PM 20205942 ER PT J AU McGurk, R Seco, J Riboldi, M Wolfgang, J Segars, P Paganetti, H AF McGurk, Ross Seco, Joao Riboldi, Marco Wolfgang, John Segars, Paul Paganetti, Harald TI Extension of the NCAT phantom for the investigation of intra-fraction respiratory motion in IMRT using 4D Monte Carlo SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; ORGAN MOTION; DOSE CALCULATIONS; TUMOR MOTION; LUNG IMRT; MULTILEAF COLLIMATOR; HUMAN ANATOMY; RADIOTHERAPY; SIMULATION; MODEL AB The purpose of this work was to create a computational platform for studying motion in intensity modulated radiotherapy (IMRT). Specifically, the non-uniform rational B-spline (NURB) cardiac and torso (NCAT) phantom was modified for use in a four-dimensional Monte Carlo (4D-MC) simulation system to investigate the effect of respiratory-induced intra-fraction organ motion on IMRT dose distributions as a function of diaphragm motion, lesion size and lung density. Treatment plans for four clinical scenarios were designed: diaphragm peak-to-peak amplitude of 1 cm and 3 cm, and two lesion sizes 2 cm and 4 cm diameter placed in the lower lobe of the right lung. Lung density was changed for each phase using a conservation of mass calculation. Further, a new heterogeneous lung model was implemented and tested. Each lesion had an internal target volume (ITV) subsequently expanded by 15 mm isotropically to give the planning target volume (PTV). The PTV was prescribed to receive 72 Gy in 40 fractions. The MLC leaf sequence defined by the planning system for each patient was exported and used as input into the MC system. MC simulations using the dose planning method (DPM) code together with deformable image registration based on the NCAT deformation field were used to find a composite dose distribution for each phantom. These composite distributions were subsequently analyzed using information from the dose volume histograms (DVH). Lesion motion amplitude has the largest effect on the dose distribution. Tumor size was found to have a smaller effect and can be mitigated by ensuring the planning constraints are optimized for the tumor size. The use of a dynamic or heterogeneous lung density model over a respiratory cycle does not appear to be an important factor with a <= 0.6% change in the mean dose received by the ITV, PTV and right lung. The heterogeneous model increases the realism of the NCAT phantom and may provide more accurate simulations in radiation therapy investigations that use the phantom. This work further evaluates the NCAT phantom for use as a tool in radiation therapy research in addition to its extensive use in diagnostic imaging and nuclear medicine research. Our results indicate that the NCAT phantom, combined with 4D-MC simulations, is a useful tool in radiation therapy investigations and may allow the study of relative effects in many clinically relevant situations. C1 [McGurk, Ross; Seco, Joao; Wolfgang, John; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Seco, Joao; Wolfgang, John; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Riboldi, Marco] Politecn Milano Univ, Dept Bioengn, TBMLab, I-20133 Milan, Italy. [Segars, Paul] Duke Univ, Dept Radiol, Carl E Ravin Adv Imaging Labs, Durham, NC 27705 USA. RP McGurk, R (reprint author), Duke Univ, Med Phys Grad Program, Durham, NC 27705 USA. EM ross.mcgurk@duke.edu RI Seco, Joao/J-4451-2012; Riboldi, Marco/I-2980-2014 OI Riboldi, Marco/0000-0002-2431-4966 FU Fulbright New Zealand Science and Technology Scholarship; NIH [R01-CA 111590] FX This work was supported by a Fulbright New Zealand Science and Technology Scholarship and by the NIH under R01-CA 111590 'Four-dimensional Monte Carlo dose calculation'. NR 52 TC 11 Z9 12 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 7 PY 2010 VL 55 IS 5 BP 1475 EP 1490 DI 10.1088/0031-9155/55/5/014 PG 16 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 555YY UT WOS:000274554100014 PM 20157230 ER PT J AU Ramanathan, L Hu, SX Frautschy, SA Siegel, JM AF Ramanathan, Lalini Hu, Shuxin Frautschy, Sally A. Siegel, Jerome M. TI Short-term total sleep deprivation in the rat increases antioxidant responses in multiple brain regions without impairing spontaneous alternation behavior SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Total sleep deprivation; Y maze; Metabolic activity; Antioxidant responses; Rat ID GLUTATHIONE DEPLETION; SUPEROXIDE-DISMUTASE; PARADOXICAL SLEEP; OXIDATIVE STRESS; SPATIAL MEMORY; HIPPOCAMPUS; DECREASES; ENZYMES; MICE; FRAGMENTATION AB Total sleep deprivation (TSD) induces a broad spectrum of cognitive, behavioral and cellular changes. We previously reported that long term (5-11 days) TSD in the rat, by the disk-over-water method, decreases the activity of the antioxidant enzyme superoxide dismutase (SOD) in the brainstem and hippocampus. To gain insight into the mechanisms causing cognitive impairment, here we explore the early associations between metabolic activity, antioxidant responses and working memory (one form of cognitive impairment). Specifically we investigated the impact of short-term (6h) TSD, by gentle handling, on the levels of the endogenous antioxidant, total glutathione (GSHt), and the activities of the antioxidative enzymes, SOD and glutathione peroxidase (GPx). Short-term TSD had no significant impact on SOD activity, but increased GSHt levels in the rat cortex, brainstem and basal forebrain, and GPx activity in the rat hippocampus and cerebellum. We also observed increased activity of hexokinase, (HK), the rate limiting enzyme of glucose metabolism, in the rat cortex and hypothalamus. We further showed that 6 h of TSD leads to increased exploratory behavior to a new environment, without impairing spontaneous alternation behavior (SAB) in the Y maze. We conclude that acute (6 h) sleep loss may trigger compensatory mechanisms (like increased antioxidant responses) that prevent initial deterioration in working memory. Published by Elsevier B.V. C1 [Ramanathan, Lalini; Siegel, Jerome M.] Greater Los Angeles Hlth Care Syst, Neurobiol Res 151A3, North Hills, CA USA. [Ramanathan, Lalini; Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Hu, Shuxin; Frautschy, Sally A.] Greater Los Angeles Hlth Care Syst, Geriatr Res & Educ Clin Ctr 151A3, North Hills, CA USA. [Hu, Shuxin; Frautschy, Sally A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Frautschy, Sally A.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. RP Siegel, JM (reprint author), VA GLAHS Sepulveda, Neurobiol Res 151A3,16111 Plummer St, North Hills, CA 91343 USA. EM jsiegel@ucla.edu RI Sanguansri, Luz/B-6630-2011 OI Sanguansri, Luz/0000-0003-1908-7604 FU Department of Veteran Affairs [HL-060296, HL-41370, MH-64109] FX This research was supported by grants HL-060296, HL-41370 and MH-64109 and by the Medical Research Services of the Department of Veteran Affairs. NR 31 TC 17 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAR 5 PY 2010 VL 207 IS 2 BP 305 EP 309 DI 10.1016/j.bbr.2009.10.014 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 558RC UT WOS:000274761800009 PM 19850085 ER PT J AU Heinrichs, SC Leite-Morris, KA Carey, RJ Kaplan, GB AF Heinrichs, S. C. Leite-Morris, K. A. Carey, R. J. Kaplan, G. B. TI Baclofen enhances extinction of opiate conditioned place preference SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Opiate; Baclofen; Conditioning; Extinction; Reconsolidation; Reward; Mouse ID VENTROMEDIAL PREFRONTAL CORTEX; STIMULUS-REWARD MEMORY; COCAINE-SEEKING; D-CYCLOSERINE; BASOLATERAL AMYGDALA; FEAR EXTINCTION; RATS; DRUG; REINSTATEMENT; AGONIST AB Conditioned opiate reward (COR) is rapidly acquired and slowly extinguished. The slow rate of extinction of the salience of drug-related cues contributes to drug craving and relapse. The gamma-aminobutyric acid receptor type B (GABA(B)) agonist, baclofen, attenuates the unconditioned rewarding actions of several drugs of abuse and was investigated for effects on the extinction of COR. C57BL/6 mice were utilized in an unbiased conditioned place preference (CPP) protocol using morphine (10 mg/kg, s.c.) and saline. CPP was measured by increases in time spent in the morphine-associated (CS+) vs. the saline-associated (CS-) chamber in a 15-min test after four morphine and four saline alternated conditioning sessions. CPP and locomotor sensitization were produced to the CS+ chamber. Subsequently, sixteen daily extinction sessions were conducted with eithervehicle or baclofen (1 or 2.5 mg/kg, s.c.) treatment given either before or after the sessions. This design was used to create the baclofen drug state before or after the activation of the CPP memory trace in the extinction protocol. After morphine CPP development, its extinction was significantly facilitated in a dose-dependent manner by post-session, but not by pre-session, baclofen treatments. No significant sedative effects of baclofen were detected during any extinction training or testing phase. Baclofen treatment facilitated the extinction of COR and reduced conditioned sensitization during extinction when given after, but not before, the activation of the CPP memory trace. Baclofen appears to have disrupted reconsolidation of conditioned reward memory during extinction training and might similarly facilitate extinction learning in human opiate addiction. (C) 2009 Elsevier B.V. All rights reserved. C1 [Leite-Morris, K. A.; Kaplan, G. B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Leite-Morris, K. A.; Kaplan, G. B.] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA. [Leite-Morris, K. A.; Kaplan, G. B.] Boston Univ, Sch Med, Dept Expt Therapeut, Boston, MA 02118 USA. [Kaplan, G. B.] Mental Hlth Serv, Boston, MA USA. [Heinrichs, S. C.; Leite-Morris, K. A.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Carey, R. J.] VA Med Ctr, Res & Dev, Syracuse, NY USA. [Carey, R. J.] SUNY Hlth Sci Ctr, Syracuse, NY 13210 USA. RP Leite-Morris, KA (reprint author), VA Boston Healthcare Syst 116A, 150 S Huntington Ave, Boston, MA 02130 USA. EM Gary.Kaplan@va.gov OI Leite-Morris, Kimberly/0000-0003-3407-7375 FU Department of Veterans Affairs FX The authors gratefully acknowledge the technical assistance of Angela Pieroni and Cynthia Philip. This research was supported by a grant from the Department of Veterans Affairs. The funding agency had no involvement in study design, collection, analysis or interpretation of the data, writing of the report or decision to submit the paper for publication. Authors Heinrichs, Leite-Morris, Carey and Kaplan designed the study. Author Heinrichs collected the behavioral measures, undertook the statistical analysis, and wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript. NR 45 TC 26 Z9 30 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAR 5 PY 2010 VL 207 IS 2 BP 353 EP 359 DI 10.1016/j.bbr.2009.10.013 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 558RC UT WOS:000274761800014 PM 19840820 ER PT J AU Abraham, S Sheridan, SD Laurent, LC Albert, K Stubban, C Ulitsky, I Miller, B Loring, JF Rao, RR AF Abraham, Sheena Sheridan, Steven D. Laurent, Louise C. Albert, Kelsey Stubban, Christopher Ulitsky, Igor Miller, Bradley Loring, Jeanne F. Rao, Raj R. TI Propagation of human embryonic and induced pluripotent stem cells in an indirect co-culture system SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Human pluripotent stem cells; Microporous membranes; Indirect co-culture; Cell separation ID REAL-TIME PCR; HUMAN BLASTOCYSTS; LINES; CULTURE; DIFFERENTIATION AB We have developed and validated a microporous poly(ethylene terephthalate) membrane-based indirect co-culture system for human pluripotent stem cell (hPSC) propagation, which allows real-time conditioning of the culture medium with human fibroblasts while maintaining the complete separation of the two cell types. The propagation and pluripotent characteristics of a human embryonic stem cell (hESC) line and a human induced pluripotent stem cell (hiPSC) line were studied in prolonged culture in this system. We report that hPSCs cultured on membranes by indirect co-culture with fibroblasts were indistinguishable by multiple criteria from hPSCs cultured directly on a fibroblast feeder layer. Thus this co-culture system is a significant advance in hPSC culture methods, providing a facile stem cell expansion system with continuous medium conditioning while preventing mixing of hPSCs and feeder cells. This membrane culture method will enable testing of novel feeder cells and differentiation studies using co-culture with other cell types, and will simplify stepwise changes in culture conditions for staged differentiation protocols. (C) 2010 Elsevier Inc. All rights reserved. C1 [Sheridan, Steven D.; Loring, Jeanne F.] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Abraham, Sheena; Albert, Kelsey; Rao, Raj R.] Virginia Commonwealth Univ, Richmond, VA USA. [Sheridan, Steven D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Laurent, Louise C.] Scripps Res Inst, Ctr Regenerat Med, La Jolla, CA 92037 USA. [Laurent, Louise C.] Univ Calif San Diego, San Diego, CA 92103 USA. [Stubban, Christopher; Loring, Jeanne F.] Burnham Inst Med Res, La Jolla, CA USA. [Ulitsky, Igor] Tel Aviv Univ, Sch Comp Sci, Tel Aviv, Israel. [Miller, Bradley] Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA. RP Loring, JF (reprint author), MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, E25-618, Cambridge, MA 02139 USA. EM jloring@scripps.edu; rrrao@vcu.edu OI Ulitsky, Igor/0000-0003-0555-6561 FU NIH [5K12HD000849-20, T15 HL085028-01, T15-HL074303]; CIRM [RN2-00931]; Tel Aviv University; Israel Science Foundation [385/06]; Alzheimer's Association [IIRG-05-14975, CIRM RT1-01108]; NSF-CAREER [0744556] FX Funding in part was provided by NIH 5K12HD000849-20 (L.C.L.), CIRM RN2-00931 (L.C.L.), Tel Aviv University (IU), Israel Science Foundation 385/06 (R.S.), NIH T15 HL085028-01 (J.F.L.), Alzheimer's Association IIRG-05-14975 (J.F.L.), CIRM RT1-01108 (J.F.L.), NSF-CAREER 0744556 (R.R.R.), NIH T15-HL074303 (R.R.R.). NR 23 TC 8 Z9 8 U1 0 U2 6 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 MAR 5 PY 2010 VL 393 IS 2 BP 211 EP 216 DI 10.1016/j.bbrc.2010.01.101 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 573WT UT WOS:000275946700006 PM 20117095 ER PT J AU Eiring, AM Harb, JG Neviani, P Garton, C Oaks, JJ Spizzo, R Liu, SJ Schwind, S Santhanam, R Hickey, CJ Becker, H Chandler, JC Andino, R Cortes, J Hokland, P Huettner, CS Bhatia, R Roy, DC Liebhaber, SA Caligiuri, MA Marcucci, G Garzon, R Croce, CM Calin, GA Perrotti, D AF Eiring, Anna M. Harb, Jason G. Neviani, Paolo Garton, Christopher Oaks, Joshua J. Spizzo, Riccardo Liu, Shujun Schwind, Sebastian Santhanam, Ramasamy Hickey, Christopher J. Becker, Heiko Chandler, Jason C. Andino, Raul Cortes, Jorge Hokland, Peter Huettner, Claudia S. Bhatia, Ravi Roy, Denis C. Liebhaber, Stephen A. Caligiuri, Michael A. Marcucci, Guido Garzon, Ramiro Croce, Carlo M. Calin, George A. Perrotti, Danilo TI miR-328 Functions as an RNA Decoy to Modulate hnRNP E2 Regulation of mRNA Translation in Leukemic Blasts SO CELL LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; FRAGILE-X-SYNDROME; C/EBP-ALPHA; CD34(+) CELLS; HUMAN CANCER; EXPRESSION; BCR/ABL; MICRORNAS; BINDING; DIFFERENTIATION AB MicroRNAs and heterogeneous ribonucleoproteins (hnRNPs) are posttranscriptional gene regulators that bind mRNA in a sequence-specific manner. Here, we report that loss of miR-328 occurs in blast crisis chronic myelogenous leukemia (CML-BC) in a BCR/ABL dose- and kinase-dependent manner through the MAPK-hnRNP E2 pathway. Restoration of miR-328 expression rescues differentiation and impairs survival of leukemic blasts by simultaneously interacting with the translational regulator poly(rC)-binding protein hnRNP E2 and with the mRNA encoding the survival factor PIM1, respectively. The interaction with hnRNP E2 is independent of the microRNA's seed sequence and it leads to release of CEBPA mRNA from hnRNP E2-mediated translational inhibition. Altogether, these data reveal the dual ability of a microRNA to control cell fate both through base pairing with mRNA targets and through a decoy activity that interferes with the function of regulatory proteins. C1 [Eiring, Anna M.; Harb, Jason G.; Neviani, Paolo; Garton, Christopher; Oaks, Joshua J.; Santhanam, Ramasamy; Caligiuri, Michael A.; Marcucci, Guido; Garzon, Ramiro; Croce, Carlo M.; Perrotti, Danilo] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Human Canc Genet Program, Columbus, OH 43210 USA. [Liu, Shujun; Schwind, Sebastian; Hickey, Christopher J.; Becker, Heiko; Chandler, Jason C.; Caligiuri, Michael A.; Marcucci, Guido; Garzon, Ramiro] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Schwind, Sebastian; Hickey, Christopher J.; Becker, Heiko; Caligiuri, Michael A.; Marcucci, Guido; Garzon, Ramiro; Croce, Carlo M.; Perrotti, Danilo] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Perrotti, Danilo] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA. [Andino, Raul] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [Spizzo, Riccardo; Cortes, Jorge; Calin, George A.] Univ Texas Houston, MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNAs, Dept Leukemia, Houston, TX 77030 USA. [Spizzo, Riccardo; Cortes, Jorge; Calin, George A.] Univ Texas Houston, MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNAs, Dept Expt Therapeut, Houston, TX 77030 USA. [Hokland, Peter] Aarhus Univ, Dept Hematol, DK-8000 Aarhus C, Denmark. [Huettner, Claudia S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bhatia, Ravi] City Hope Natl Med Ctr, Dept Hematopoiet Stem Cell & Leukemia Res, Duarte, CA 91010 USA. [Roy, Denis C.] Hop Maison Neuve Rosemont, Dept Hematol Oncol, Montreal, PQ H3T 1J4, Canada. [Roy, Denis C.] Univ Montreal, Montreal, PQ H3T 1J4, Canada. [Liebhaber, Stephen A.] Univ Penn, Sch Med, Dept Genet & Med, Philadelphia, PA 19104 USA. RP Perrotti, D (reprint author), Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Human Canc Genet Program, Columbus, OH 43210 USA. EM danilo.perrotti@osumc.edu RI Garzon, Ramiro/E-3104-2011; Perrotti, Danilo/E-3852-2011; OI Spizzo, Riccardo/0000-0001-7772-0960; Hokland, Peter/0000-0002-1177-9756 FU National Cancer Institute [CA095512, CA16058]; NIH, Bethesda, MD, USA; US Army [W81XWH-07-1-0270]; American-Italian Cancer Foundation; Fonds de la Recherche en Sante du Quebec; OSU Graduate School; Leukemia and Lymphoma Society; M.D. Anderson Research Trust; University of Texas System Regents FX This work was supported in part by grants from the National Cancer Institute CA095512 (D.P.), CA16058 (OSU-CCC), NIH, Bethesda, MD, USA; the US Army, CML Research Program, W81XWH-07-1-0270 (D. P.); the American-Italian Cancer Foundation (P.N.); Fonds de la Recherche en Sante du Quebec (D.C.R.); and AGGRS from The OSU Graduate School (A.M.E.). D.P. is a Scholar of The Leukemia and Lymphoma Society. G.A.C. is a Fellow of the M.D. Anderson Research Trust and Scholar of the University of Texas System Regents. We thank J.-S. Chang, M. Odeh, and A. Martin for technical assistance and S. Lee for editorial assistance; T. Skorski (Temple University, Philadelphia, PA, USA) for providing PIM1 cDNAs; F. Racke ( OSU, Columbus OH, USA) for histopathology analysis; B. Calabretta (TJU, Philadelphia, PA, USA), R. Arlinghaus ( MDACC, Houston, TX, USA), and K. Huebner (OSU) for critical reading of the manuscript. NR 45 TC 256 Z9 278 U1 5 U2 33 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 5 PY 2010 VL 140 IS 5 BP 652 EP 665 DI 10.1016/j.cell.2010.01.007 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 564EZ UT WOS:000275197400015 PM 20211135 ER PT J AU North, TE Goessling, W AF North, Trista E. Goessling, Wolfram TI NOTCHing an Arrow at Cord Blood: Translating Stem Cell Knowledge into Clinical Practice SO CELL STEM CELL LA English DT Editorial Material ID TRANSPLANTATION; EXPANSION AB Umbilical cord transplants have emerged as an important therapeutic option for patients with leukemia and lymphoma. A recent study in Nature Medicine highlights the potential and challenges of translating cell-based therapies to the clinic. C1 [North, Trista E.] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [North, Trista E.; Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Genet,Med Sch, Boston, MA 02115 USA. [North, Trista E.; Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Gastroenterol,Med Sch, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP North, TE (reprint author), Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. EM tnorth@bidmc.harvard.edu; wgoessling@partners.org NR 10 TC 5 Z9 5 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAR 5 PY 2010 VL 6 IS 3 BP 186 EP 187 DI 10.1016/j.stem.2010.02.009 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 577WL UT WOS:000276254600003 PM 20207217 ER PT J AU Sanda, T Li, X Gutierrez, A Ahn, Y Neuberg, DS O'Neil, J Strack, PR Winter, CG Winter, SS Larson, RS von Boehmer, H Look, AT AF Sanda, Takaomi Li, Xiaoyu Gutierrez, Alejandro Ahn, Yebin Neuberg, Donna S. O'Neil, Jennifer Strack, Peter R. Winter, Christopher G. Winter, Stuart S. Larson, Richard S. von Boehmer, Harald Look, A. Thomas TI Interconnecting molecular pathways in the pathogenesis and drug sensitivity of T-cell acute lymphoblastic leukemia SO BLOOD LA English DT Article ID NF-KAPPA-B; HISTONE DEACETYLASE INHIBITOR; GENE-EXPRESSION SIGNATURES; TUMOR-SUPPRESSOR; C-MYC; HOMOZYGOUS DELETIONS; SIGNALING PATHWAY; MTS1 P16(INK4A); NOTCH1; CHILDHOOD AB To identify dysregulated pathways in distinct phases of NOTCH1-mediated T-cell leukemogenesis, as well as small-molecule inhibitors that could synergize with or substitute for gamma-secretase inhibitors (GSIs) in T-cell acute lymphoblastic leukemia (T-ALL) therapy, we compared gene expression profiles in a Notch1-induced mouse model of T-ALL with those in human T-ALL. The overall patterns of NOTCH1-mediated gene expression in human and mouse T-ALLs were remarkably similar, as defined early in transformation in the mouse by the regulation of MYC and its target genes and activation of nuclear factor-kappa B and PI3K/AKT pathways. Later events in murine Notch1-mediated leukemogenesis included down-regulation of genes encoding tumor suppressors and negative cell cycle regulators. Gene set enrichment analysis and connectivity map algorithm predicted that small-molecule inhibitors, including heat-shock protein 90, histone deacetylase, PI3K/AKT, and proteasome inhibitors, could reverse the gene expression changes induced by NOTCH1. When tested in vitro, histone deacetylase, PI3K and proteasome inhibitors synergized with GSI in suppressing T-ALL cell growth in GSI-sensitive cells. Interestingly, alvespimycin, a potent inhibitor of the heat-shock protein 90 molecular chaperone, markedly inhibited the growth of both GSI-sensitive and -resistant T-ALL cells, suggesting that its loss disrupts signal transduction pathways crucial for the growth and survival of T-ALL cells. (Blood. 2010;115:1735-1745) C1 [Li, Xiaoyu; von Boehmer, Harald] Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sanda, Takaomi; Gutierrez, Alejandro; Ahn, Yebin; O'Neil, Jennifer; Look, A. Thomas] Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. [Gutierrez, Alejandro] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Neuberg, Donna S.] Harvard Univ, Dept Biostat & Computat Biol, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Strack, Peter R.; Winter, Christopher G.] Merck Res Labs, Boston, MA USA. [Winter, Stuart S.] Univ New Mexico, Hlth Sci Ctr, Dept Pediat, Albuquerque, NM 87131 USA. [Larson, Richard S.] Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87131 USA. RP von Boehmer, H (reprint author), Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Dana Farber Canc Inst, 44 Binney St,Smith 736, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu; thomas_look@dfci.harvard.edu OI Gutierrez, Alejandro/0000-0002-0249-9007 FU National Cancer Institute [5P01CA109901-040001]; Lymphoma Research Foundation; Claudia Adams Barr; [COG 9900]; [CA98543]; [CA114766] FX This work was supported by the National Cancer Institute (grant 5P01CA109901-040001; A. T. L. and H. v. B) and by the Lymphoma Research Foundation fellowship and the Claudia Adams Barr grant (X. L.). COG cell banking and sample distribution were supported by the COG 9900 cell biology study and grants CA98543 and CA114766. NR 46 TC 30 Z9 30 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 MAR 4 PY 2010 VL 115 IS 9 BP 1735 EP 1745 DI 10.1182/blood-2009-07-235143 PG 11 WC Hematology SC Hematology GA 571KR UT WOS:000275751200014 PM 20007543 ER PT J AU Robledo, RF Lambert, AJ Birkenmeier, CS Cirlan, MV Cirlan, AFM Campagna, DR Lux, SE Peters, LL AF Robledo, Raymond F. Lambert, Amy J. Birkenmeier, Connie S. Cirlan, Marius V. Cirlan, Andreea Flavia M. Campagna, Dean R. Lux, Samuel E. Peters, Luanne L. TI Analysis of novel sph (spherocytosis) alleles in mice reveals allele-specific loss of band 3 and adducin in alpha-spectrin-deficient red cells SO BLOOD LA English DT Article ID HEMATOLOGICALLY IMPORTANT MUTATIONS; HERMANSKY-PUDLAK-SYNDROME; MESSENGER-RNA DECAY; MEMBRANE SKELETON; HEREDITARY ELLIPTOCYTOSIS; ERYTHROCYTE-MEMBRANE; MOUSE MODEL; ANKYRIN VARIANTS; HEMOLYTIC-ANEMIA; ALTERED LEVELS AB Five spontaneous, allelic mutations in the alpha-spectrin gene, Spna1, have been identified in mice (spherocytosis [sph], sph(1J), sph(2J), sph(2BC), sph(Dem)). All cause severe hemolytic anemia. Here, analysis of 3 new alleles reveals previously unknown consequences of red blood cell (RBC) spectrin deficiency. In sph(3J), a missense mutation (H2012Y) in repeat 19 introduces a cryptic splice site resulting in premature termination of translation. In sph(Ihj), a premature stop codon occurs (Q1853Stop) in repeat 18. Both mutations result in markedly reduced RBC membrane spectrin content, decreased band 3, and absent beta-adducin. Reevaluation of available, previously described sph alleles reveals band 3 and adducin deficiency as well. In sph(4J), a missense mutation occurs in the C-terminal EF hand domain (C2384Y). Notably, an equally severe hemolytic anemia occurs despite minimally decreased membrane spectrin with normal band 3 levels and present, although reduced, beta-adducin. The severity of anemia in sph(4J) indicates that the highly conserved cysteine residue at the C-terminus of alpha-spectrin participates in interactions critical to membrane stability. The data reinforce the notion that a membrane bridge in addition to the classic protein 4.1-p55-glycophorin C linkage exists at the RBC junctional complex that involves interactions between spectrin, adducin, and band 3. (Blood. 2010;115:1804-1814) C1 [Robledo, Raymond F.; Lambert, Amy J.; Birkenmeier, Connie S.; Peters, Luanne L.] Jackson Lab, Bar Harbor, ME 04609 USA. [Cirlan, Marius V.] Petre Andrei Univ, Fac Med Dent, Iasi, Romania. [Cirlan, Andreea Flavia M.] Univ Agr Sci & Vet Med, Fac Vet Med, Iasi, Romania. [Campagna, Dean R.] Childrens Hosp Boston, Div Pathol, Boston, MA USA. [Lux, Samuel E.] Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp Boston, Boston, MA USA. [Lux, Samuel E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Peters, LL (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM luanne.peters@jax.org FU National Institutes of Health [HL088468, HL075714, HL081608]; Jackson Laboratory Mouse Mutant Resource [RR01183]; National Cancer Institute [CA34196] FX This work was supported by National Institutes of Health grants HL088468 and HL075714 (to L. L. P.), HL081608 (to S. E. L.); RR01183 (The Jackson Laboratory Mouse Mutant Resource); and The National Cancer Institute (CA34196, The Jackson Laboratory). NR 53 TC 7 Z9 7 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 4 PY 2010 VL 115 IS 9 BP 1804 EP 1814 DI 10.1182/blood-2009-07-232199 PG 11 WC Hematology SC Hematology GA 571KR UT WOS:000275751200022 PM 20056793 ER PT J AU Canault, M Duerschmied, D Brill, A Stefanini, L Schatzberg, D Cifuni, SM Bergmeier, W Wagner, DD AF Canault, Matthias Duerschmied, Daniel Brill, Alexander Stefanini, Lucia Schatzberg, Daphne Cifuni, Stephen M. Bergmeier, Wolfgang Wagner, Denisa D. TI p38 mitogen-activated protein kinase activation during platelet storage: consequences for platelet recovery and hemostatic function in vivo SO BLOOD LA English DT Article ID ALPHA-CONVERTING-ENZYME; CYTOSOLIC PHOSPHOLIPASE A(2); MAP KINASE; ARACHIDONIC-ACID; GLYCOPROTEIN-IB; MOUSE MODEL; PHOSPHORYLATION; INHIBITION; ADAM17; VITRO AB Platelets undergo several modifications during storage that reduce their post-transfusion survival and functionality. One important feature of these changes, which are known as platelet storage lesion, is the shedding of the surface glycoproteins GPIb-alpha and GPV. We recently demonstrated that tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) mediates mitochondrial injury-induced shedding of adhesion receptors and that TACE activity correlates with reduced posttransfusion survival of these cells. We now confirm that TACE mediates receptor shedding and clearance of platelets stored for 16 hours at 37 degrees C or 22 degrees C. We further demonstrate that both storage and mitochondrial injury lead to the phosphorylation of p38 mitogen-activated kinase (MAPK) in platelets and that TACE-mediated receptor shedding from mouse and human platelets requires p38 MAP kinase signaling. Protein kinase C, extracellular regulated-signal kinase MAPK, and caspases were not involved in TACE activation. Both inhibition of p38 MAPK and inactivation of TACE during platelet storage led to a markedly improved posttransfusion recovery and hemostatic function of platelets in mice. p38 MAPK inhibitors had only minor effects on the aggregation of fresh platelets under static or flow conditions in vitro. In summary, our data suggest that inhibition of p38 MAPK or TACE during storage may significantly improve the quality of stored platelets. (Blood. 2010;115:1835-1842) C1 [Canault, Matthias; Duerschmied, Daniel; Brill, Alexander; Schatzberg, Daphne; Cifuni, Stephen M.; Wagner, Denisa D.] Immune Dis Inst, Boston, MA 02115 USA. [Canault, Matthias; Duerschmied, Daniel; Brill, Alexander; Schatzberg, Daphne; Cifuni, Stephen M.; Wagner, Denisa D.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. [Canault, Matthias; Duerschmied, Daniel; Brill, Alexander; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Stefanini, Lucia; Bergmeier, Wolfgang] Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA. [Stefanini, Lucia; Bergmeier, Wolfgang] Thomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19107 USA. RP Wagner, DD (reprint author), Immune Dis Inst, 3 Blackfan Cir, Boston, MA 02115 USA. EM wolfgang.bergmeier@jefferson.edu; wagner@idi.harvard.edu RI Silva, Mariana/B-9530-2012; stefanini, lucia/K-3992-2016; Canault, Matthias/H-5128-2013 OI stefanini, lucia/0000-0001-7420-301X; Canault, Matthias/0000-0002-7880-5250 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [P01 HL056949]; American Heart Association [0630044N] FX This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (grant P01 HL056949; D. D. W.) and the American Heart Association (Scientist Development grant 0630044N; W. B.). NR 36 TC 39 Z9 42 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 4 PY 2010 VL 115 IS 9 BP 1835 EP 1842 DI 10.1182/blood-2009-03-211706 PG 8 WC Hematology SC Hematology GA 571KR UT WOS:000275751200025 PM 19965619 ER PT J AU Litzow, MR Tarima, S Perez, WS Bolwell, BJ Cairo, MS Camitta, BM Cutler, CS de Lima, M DiPersio, JF Gale, RP Keating, A Lazarus, HM Luger, S Marks, DI Maziarz, RT McCarthy, PL Pasquini, MC Phillips, GL Rizzo, JD Sierra, J Tallman, MS Weisdorf, DJ AF Litzow, Mark R. Tarima, Sergey Perez, Waleska S. Bolwell, Brian J. Cairo, Mitchell S. Camitta, Bruce M. Cutler, Corey S. de Lima, Marcos DiPersio, John F. Gale, Robert Peter Keating, Armand Lazarus, Hillard M. Luger, Selina Marks, David I. Maziarz, Richard T. McCarthy, Philip L. Pasquini, Marcelo C. Phillips, Gordon L. Rizzo, J. Douglas Sierra, Jorge Tallman, Martin S. Weisdorf, Daniel J. TI Allogeneic transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; ACUTE NONLYMPHOCYTIC LEUKEMIA; DOSE CYTOSINE-ARABINOSIDE; LATE COMPLICATION; HOST DISEASE; RISK-FACTORS; LYMPHOMA; CHEMOTHERAPY; CYTOGENETICS AB Therapy-related myelodysplastic syndromes (t-MDSs) and acute myeloid leukemia (t-AML) have a poor prognosis with conventional therapy. Encouraging results are reported after allogeneic transplantation. We analyzed outcomes in 868 persons with t-AML (n = 545) or t-MDS (n = 323) receiving allogeneic transplants from 1990 to 2004. A myeloablative regimen was used for conditioning in 77%. Treatment-related mortality (TRM) and relapse were 41% (95% confidence interval [CI], 38-44) and 27% (24-30) at 1 year and 48% (44-51) and 31% (28-34) at 5 years, respectively. Disease-free (DFS) and overall survival (OS) were 32% (95% CI, 29-36) and 37% (34-41) at 1 year and 21% (18-24) and 22% (19-26) at 5 years, respectively. In multivariate analysis, 4 risk factors had adverse impacts on DFS and OS: (1) age older than 35 years; (2) poor-risk cytogenetics; (3) t-AML not in remission or advanced t-MDS; and (4) donor other than an HLA-identical sibling or a partially or well-matched unrelated donor. Five-year survival for subjects with none, 1, 2, 3, or 4 of these risk factors was 50% (95% CI, 38-61), 26% (20-31), 21% (16-26), 10% (5-15), and 4% (0-16), respectively (P < .001). These data permit a more precise prediction of outcome and identify subjects most likely to benefit from allogeneic transplantation. (Blood. 2010; 115: 1850-1857) C1 [Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Adult Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Perez, Waleska S.; Pasquini, Marcelo C.; Rizzo, J. Douglas] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Bolwell, Brian J.] Cleveland Clin Fdn, Cleveland, OH USA. [Cairo, Mitchell S.] Morgan Stanley Childrens Hosp NY Presbyterian, New York, NY USA. [Camitta, Bruce M.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [de Lima, Marcos] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [DiPersio, John F.] St Louis Childrens Hosp, St Louis, MO USA. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Keating, Armand] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Lazarus, Hillard M.] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [Luger, Selina] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Marks, David I.] United Bristol Healthcare, Bristol, Avon, England. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Phillips, Gordon L.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Sierra, Jorge] Hosp Santa Cruz & Sant Pau, Barcelona, Spain. [Tallman, Martin S.] NW Mem Hosp, Chicago, IL 60611 USA. RP Weisdorf, DJ (reprint author), Univ Minnesota, Med Ctr, Adult Blood & Marrow Transplant Program, MMC 480,516 Delaware St SE, Minneapolis, MN 55455 USA. EM weisd001@umn.edu RI Lopez, Dulce/A-7700-2013 FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI) [5U01HL069294]; National Institute of Allergy and Infectious Diseases (NIAID); 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 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); Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; 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, Bio Marin 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, Genen-tech 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, StemCyte Inc, StemSoft Software Inc, Sysmex America Inc, Teva Pharmaceutical Industries, THERAKOS Inc, Thermogenesis Corporation, Vidacare Corporation, Vion Pharmaceuticals Inc, ViraCor Laboratories, ViroPharma Inc, and Wellpoint Inc. NR 30 TC 82 Z9 89 U1 3 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 4 PY 2010 VL 115 IS 9 BP 1850 EP 1857 DI 10.1182/blood-2009-10-249128 PG 8 WC Hematology SC Hematology GA 571KR UT WOS:000275751200027 PM 20032503 ER PT J AU Hirschey, MD Shimazu, T Goetzman, E Jing, E Schwer, B Lombard, DB Grueter, CA Harris, C Biddinger, S Ilkayeva, OR Stevens, RD Li, Y Saha, AK Ruderman, NB Bain, JR Newgard, CB Farese, RV Alt, F Kahn, CR Verdin, E AF Hirschey, Matthew D. Shimazu, Tadahiro Goetzman, Eric Jing, Enxuan Schwer, Bjoern Lombard, David B. Grueter, Carrie A. Harris, Charles Biddinger, Sudha Ilkayeva, Olga R. Stevens, Robert D. Li, Yu Saha, Asish K. Ruderman, Neil B. Bain, James R. Newgard, Christopher B. Farese, Robert V., Jr. Alt, FrederickW. Kahn, C. Ronald Verdin, Eric TI SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation SO NATURE LA English DT Article ID COA DEHYDROGENASE-DEFICIENCY; GENE-EXPRESSION PROFILES; LYSINE ACETYLATION; METABOLIC SYNDROME; INSULIN-RESISTANCE; HEPATIC STEATOSIS; BETA-OXIDATION; LIVER-DISEASE; IN-VIVO; MICE AB Sirtuins are NAD(+)-dependent protein deacetylases. They mediate adaptive responses to a variety of stresses, including calorie restriction and metabolic stress. Sirtuin 3 (SIRT3) is localized in the mitochondrial matrix, where it regulates the acetylation levels of metabolic enzymes, including acetyl coenzyme A synthetase 2 (refs 1, 2). Mice lacking both Sirt3 alleles appear phenotypically normal under basal conditions, but show marked hyperacetylation of several mitochondrial proteins(3). Here we report that SIRT3 expression is upregulated during fasting in liver and brown adipose tissues. During fasting, livers from mice lacking SIRT3 had higher levels of fatty-acid oxidation intermediate products and triglycerides, associated with decreased levels of fatty-acid oxidation, compared to livers from wild-type mice. Mass spectrometry of mitochondrial proteins shows that long-chain acyl coenzyme A dehydrogenase (LCAD) is hyperacetylated at lysine 42 in the absence of SIRT3. LCAD is deacetylated in wild-type mice under fasted conditions and by SIRT3 in vitro and in vivo; and hyperacetylation of LCAD reduces its enzymatic activity. Mice lacking SIRT3 exhibit hallmarks of fatty-acid oxidation disorders during fasting, including reduced ATP levels and intolerance to cold exposure. These findings identify acetylation as a novel regulatory mechanism for mitochondrial fatty-acid oxidation and demonstrate that SIRT3 modulates mitochondrial intermediary metabolism and fatty-acid use during fasting. C1 [Hirschey, Matthew D.; Shimazu, Tadahiro; Schwer, Bjoern; Verdin, Eric] Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA. [Hirschey, Matthew D.; Shimazu, Tadahiro; Schwer, Bjoern; Verdin, Eric] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Goetzman, Eric] Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15201 USA. [Jing, Enxuan; Biddinger, Sudha; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Schwer, Bjoern; Lombard, David B.; Alt, FrederickW.] Harvard Univ, Sch Med, Childrens Hosp,Immune Dis Inst,Dept Genet, Howard Hughes Med Inst,Program Cellular & Mol Med, Boston, MA 02115 USA. [Grueter, Carrie A.; Harris, Charles; Farese, Robert V., Jr.] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA. [Ilkayeva, Olga R.; Stevens, Robert D.; Bain, James R.; Newgard, Christopher B.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA. [Li, Yu] Cell Signaling Technol, Danvers, MA 01923 USA. [Saha, Asish K.; Ruderman, Neil B.] Boston Univ, Med Ctr, Diabet Unit, Boston, MA 02118 USA. [Saha, Asish K.; Ruderman, Neil B.] Boston Univ, Med Ctr, Dept Physiol & Med Biophys, Boston, MA 02118 USA. RP Verdin, E (reprint author), Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA. EM everdin@gladstone.ucsf.edu OI Grueter, Carrie/0000-0002-1913-2527; Saha, Asish/0000-0003-1001-5110; Ruderman, Neil/0000-0002-6589-6587; Verdin, Eric/0000-0003-3703-3183; Bain, James/0000-0002-8917-9187; Hirschey, Matthew/0000-0003-4541-5376 FU Elison Medical Foundation; National Institute on Aging; National Institutes of Health (NIH) [PO1 HL068758-06A1, DK019514-29, R01 DK067509-04] FX We thank T. Canavan and J. J. Maher for primary hepatocyte preparation (P30 DK026743); C. Harris, L. Swift and the Mouse Metabolic Phenotyping Center (DK59637) for analysis of plasma and tissue lipid analysis; J. Wong for electron microscopy studies, S. Mihalik and D. Cuebas for synthesis of the 2,6-dimethylheptanoyl-CoA; A.-W. Mohsen for purification of recombinant pig ETF; Y.-C. Si for assistance with adenoviral studies; A. Wilson and J. Carroll for preparation of figures; and G. Howard and S. Ordway for editorial review. This work was supported in part by a Senior Scholarship in Aging from the Elison Medical Foundation to E. V. and by institutional support from the J. David Gladstone Institutes. F. W. A. is an Investigator of the Howard Hughes Medical Institute and recipient of an Ellison Medical Foundation Senior Scholar Award. D. B. L. is supported by a K08 award from the National Institute on Aging and the National Institutes of Health. B. S. is supported by an Ellison Medical Foundation/AFAR Senior Postdoctoral Research Grant. N.B.R. and A. K. S. are supported by National Institutes of Health (NIH) grants PO1 HL068758-06A1, DK019514-29 and R01 DK067509-04. NR 43 TC 550 Z9 573 U1 13 U2 135 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 4 PY 2010 VL 464 IS 7285 BP 121 EP U137 DI 10.1038/nature08778 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 563GZ UT WOS:000275117500046 PM 20203611 ER PT J AU Hancock, EW Desai, AS Chutkow, WA Dec, GW AF Hancock, E. William Desai, Akshay S. Chutkow, William A. Dec, G. William, Jr. TI A Crisis in Late Pregnancy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Hancock, E. William] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. [Desai, Akshay S.; Chutkow, William A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dec, G. William, Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hancock, EW (reprint author), Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. EM whancock@cvmed.stanford.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 4 PY 2010 VL 362 IS 9 BP 857 EP 858 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 563DQ UT WOS:000275108300029 PM 20200395 ER PT J AU Losina, E Bassett, IV Giddy, J Chetty, S Regan, S Walensky, RP Ross, D Scott, CA Uhler, LM Katz, JN Holst, H Freedberg, KA AF Losina, Elena Bassett, Ingrid V. Giddy, Janet Chetty, Senica Regan, Susan Walensky, Rochelle P. Ross, Douglas Scott, Callie A. Uhler, Lauren M. Katz, Jeffrey N. Holst, Helga Freedberg, Kenneth A. TI The "ART" of Linkage: Pre-Treatment Loss to Care after HIV Diagnosis at Two PEPFAR Sites in Durban, South Africa SO PLOS ONE LA English DT Article ID ANTIRETROVIRAL THERAPY; FOLLOW-UP; OUTCOMES; MORTALITY; PROGRAM; DISTRICT; SERVICE; MALAWI; KENYA AB Background: Although loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa. Methodology/Principal Findings: We assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived >= 10 kilometers from the testing center (RR = 1.37; 95% CI: 1.11-1.71), had a history of tuberculosis treatment (RR = 1.26; 95% CI: 1.00-1.58), or were referred for testing by a health care provider rather than self-referred (RR = 1.61; 95% CI: 1.22-2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors. Conclusions/Significance: Nearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test. C1 [Losina, Elena; Bassett, Ingrid V.; Regan, Susan; Walensky, Rochelle P.; Scott, Callie A.; Uhler, Lauren M.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Bassett, Ingrid V.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Losina, Elena; Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA. [Losina, Elena; Katz, Jeffrey N.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Losina, Elena; Bassett, Ingrid V.; Regan, Susan; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Walensky, Rochelle P.; Katz, Jeffrey N.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Walensky, Rochelle P.; Katz, Jeffrey N.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Giddy, Janet; Chetty, Senica; Holst, Helga] McCord Hosp, Dept Med, Durban, South Africa. [Ross, Douglas] St Marys Hosp, Dept Med, Durban, South Africa. RP Losina, E (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM elosina@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X; Regan, Susan/0000-0003-0940-2017 FU US National Institute of Allergy and Infectious Diseases [R01 AI058736, K24 AI062476, K23 AI068458]; Harvard University Center for AIDS Research [P30 AI42851]; National Institutes of Health [K24 AR 02123]; Doris Duke Charitable Foundation; Harvard University FX This work was supported by the US National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, K23 AI068458), the Harvard University Center for AIDS Research P30 AI42851, National Institutes of Health K24 AR 02123, the Doris Duke Charitable Foundation (Clinical Scientist Development Award), and the Harvard University Program on AIDS (HUPA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 19 TC 106 Z9 109 U1 0 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 MAR 4 PY 2010 VL 5 IS 3 AR e9538 DI 10.1371/journal.pone.0009538 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 564EW UT WOS:000275197100018 PM 20209059 ER PT J AU Mengshol, JA Golden-Mason, L Arikawa, T Smith, M Niki, T McWilliams, R Randall, JA McMahan, R Zimmerman, MA Rangachari, M Dobrinskikh, E Busson, P Polyak, SJ Hirashima, M Rosen, HR AF Mengshol, John A. Golden-Mason, Lucy Arikawa, Tomohiro Smith, Maxwell Niki, Toshiro McWilliams, Ryan Randall, Jessica A. McMahan, Rachel Zimmerman, Michael A. Rangachari, Manu Dobrinskikh, Evgenia Busson, Pierre Polyak, Stephen J. Hirashima, Mitsuomi Rosen, Hugo R. TI A Crucial Role for Kupffer Cell-Derived Galectin-9 in Regulation of T Cell Immunity in Hepatitis C Infection SO PLOS ONE LA English DT Article ID VIRUS-INFECTION; LIVER-INJURY; HEPATOCELLULAR-CARCINOMA; GLYCAN INTERACTIONS; CD127 EXPRESSION; HCV INFECTION; LYMPHOCYTES; TOLERANCE; TIM-3; APOPTOSIS AB Approximately 200 million people throughout the world are infected with hepatitis C virus (HCV). One of the most striking features of HCV infection is its high propensity to establish persistence (similar to 70-80%) and progressive liver injury. Galectins are evolutionarily conserved glycan-binding proteins with diverse roles in innate and adaptive immune responses. Here, we demonstrate that galectin-9, the natural ligand for the T cell immunoglobulin domain and mucin domain protein 3 (Tim-3), circulates at very high levels in the serum and its hepatic expression (particularly on Kupffer cells) is significantly increased in patients with chronic HCV as compared to normal controls. Galectin-9 production from monocytes and macrophages is induced by IFN-gamma, which has been shown to be elevated in chronic HCV infection. In turn, galectin-9 induces proinflammatory cytokines in liver-derived and peripheral mononuclear cells; galectin-9 also induces anti-inflammatory cytokines from peripheral but not hepatic mononuclear cells. Galectin-9 results in expansion of CD4(+) CD25(+) FoxP3(+) CD127(low) regulatory T cells, contraction of CD4+ effector T cells, and apoptosis of HCV-specific CTLs. In conclusion, galectin-9 production by Kupffer cells links the innate and adaptive immune response, providing a potential novel immunotherapeutic target in this common viral infection. C1 [Mengshol, John A.; Golden-Mason, Lucy; McWilliams, Ryan; Randall, Jessica A.; McMahan, Rachel; Dobrinskikh, Evgenia; Rosen, Hugo R.] Univ Colorado, Sch Med, Dept Med, Div Gastroenterol & Hepatol, Aurora, CO USA. [Mengshol, John A.; Rosen, Hugo R.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Golden-Mason, Lucy; Rosen, Hugo R.] Univ Colorado, Sch Med, Div Clin Immunol, Denver, CO USA. [Golden-Mason, Lucy; Rosen, Hugo R.] Natl Jewish Hosp, Denver, CO USA. [Smith, Maxwell] Univ Colorado, Sch Med, Dept Pathol, Denver, CO 80262 USA. [Arikawa, Tomohiro; Hirashima, Mitsuomi] Kagawa Med Univ, Dept Immunol & Immunopathol, Kagawa, Japan. [Niki, Toshiro] GalPharma, Kagawa, Japan. [Zimmerman, Michael A.] Univ Colorado, Sch Med, Div Transplant Surg, Aurora, CO USA. [Rangachari, Manu] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Busson, Pierre] Inst Cancerol Gustave Roussy, Villejuif, France. [Polyak, Stephen J.] Univ Washington, Div Lab Med, Seattle, WA 98195 USA. RP Mengshol, JA (reprint author), Univ Colorado, Sch Med, Dept Med, Div Gastroenterol & Hepatol, Aurora, CO USA. EM Hugo.Rosen@ucdenver.edu RI Polyak, Stephen/B-5743-2011 FU National Institutes of Health (NIH) [RO1 DK060590, U19 A 1066328-01] FX This research is supported by National Institutes of Health (NIH) grants RO1 DK060590 and U19 A 1066328-01 (HCV center grant) to HRR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr Niki from Galpharma provided antibodies. NR 52 TC 88 Z9 95 U1 0 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 MAR 4 PY 2010 VL 5 IS 3 AR e9504 DI 10.1371/journal.pone.0009504 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 564EW UT WOS:000275197100005 PM 20209097 ER PT J AU Sopasakis, VR Liu, PX Suzuki, R Kondo, T Winnay, J Tran, TT Asano, T Smyth, G Sajan, MP Farese, RV Kahn, CR Zhao, JJ AF Sopasakis, Victoria Rotter Liu, Pixu Suzuki, Ryo Kondo, Tatsuya Winnay, Jonathon Tran, Thien T. Asano, Tomoichiro Smyth, Graham Sajan, Mini P. Farese, Robert V. Kahn, C. Ronald Zhao, Jean J. TI Specific Roles of the p110 alpha Isoform of Phosphatidylinsositol 3-Kinase in Hepatic Insulin Signaling and Metabolic Regulation SO CELL METABOLISM LA English DT Article ID PROTEIN-KINASE-C; IA PHOSPHOINOSITIDE 3-KINASES; GLUCOSE-PRODUCTION; CATALYTIC SUBUNIT; EMBRYONIC LETHALITY; DIABETES-MELLITUS; METFORMIN; LIVER; MICE; RESISTANCE AB The class I(A) phosphatidylinsositol 3-kinases (PI3Ks) form a critical node in the insulin metabolic pathway; however, the precise roles of the different isoforms of this enzyme remain elusive. Using tissue-specific gene inactivation, we demonstrate that p110 alpha catalytic subunit of PI3K is a key mediator of insulin metabolic actions in the liver. Thus, deletion of p110 alpha in liver results in markedly blunted insulin signaling with decreased generation Of PIP(3) and loss of insulin activation of Akt, defects that could not be rescued by overexpression of p110 beta. As a result, mice with hepatic knockout of p110 alpha display reduced insulin sensitivity, impaired glucose tolerance, and increased gluconeogenesis, hypolipidemia, and hyperleptinemia. The diabetic syndrome induced by loss of p110 alpha in liver did not respond to metformin treatment. Together, these data indicate that the p11 alpha isoform of PI3K plays a fundamental role in insulin signaling and control of hepatic glucose and lipid metabolism. C1 [Sopasakis, Victoria Rotter; Suzuki, Ryo; Winnay, Jonathon; Tran, Thien T.; Smyth, Graham; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Liu, Pixu; Zhao, Jean J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Kondo, Tatsuya] Kumamoto Univ, Fac Life Sci, Dept Metab Med, Kumamoto 8608556, Japan. [Asano, Tomoichiro] Hiroshima Univ, Grad Sch Biomed Sci, Hiroshima 7398551, Japan. [Sajan, Mini P.; Farese, Robert V.] James A Haley Vet Adm Med Ctr, Res Serv, Tampa, FL 33612 USA. [Sajan, Mini P.] Univ S Florida, Dept Internal Med, Tampa, FL 33612 USA. [Farese, Robert V.] Roskamp Inst, Sarasota, FL 34243 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu RI Farese, Robert/B-3605-2015 FU NIH [DK33201, DK55545, CA134502, CA089393-08S1, DK34834]; V Foundation; Claudia Barr Program; Swedish Research Council FX This work was Supported by NIH R01 grants DK33201 and DK55545 to C.R.K. and CA134502 and CA089393-08S1 to J.J.Z. Additional support came from the V Foundation (J.J.Z.), the Claudia Barr Program (J.J.Z.), the Swedish Research Council (V.R.S.), the NIH-funded Joslin Diabetes and Endocrinology Center (grant DK34834), and the Mary K. Iacocca Professorship fund. In compliance with Harvard Medical School guidelines, we disclose the consulting relationships: Novartis Pharmaceuticals, Inc. (J.J.Z.) and Sirtns/GSK Pharmaceuticals (C.R.K.). NR 44 TC 51 Z9 56 U1 1 U2 2 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 MAR 3 PY 2010 VL 11 IS 3 BP 220 EP 230 DI 10.1016/j.cmet.2010.02.002 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 565WE UT WOS:000275325400009 PM 20197055 ER PT J AU Liu, F Kozanek, M Hosseini, A Van de Velde, SK Gill, TJ Rubash, HE Li, GA AF Liu, Fang Kozanek, Michal Hosseini, Ali Van de Velde, Samuel K. Gill, Thomas J. Rubash, Harry E. Li, Guoan TI In vivo tibiofemoral cartilage deformation during the stance phase of gait SO JOURNAL OF BIOMECHANICS LA English DT Article DE Gait; Stance phase; Cartilage; Deformation; Treadmill ID LIGAMENT-DEFICIENT KNEE; JOINT CARTILAGE; KINEMATICS; CONTACT; THICKNESS; WALKING; MRI; TOPOGRAPHY; MOVEMENT; HEALTHY AB The knowledge of articular cartilage contact biomechanics in the knee joint is important for understanding the joint function and cartilage pathology. However, the in vivo tibiofemoral articular cartilage contact biomechanics during gait remains unknown. The objective of this study was to determine the in vivo tibiofemoral cartilage contact biomechanics during the stance phase of treadmill gait. Eight healthy knees were magnetic resonance (MR) scanned and imaged with a dual fluoroscopic system during gait on a treadmill. The tibia, femur and associated cartilage were constructed from the MR images and combined with the dual fluoroscopic images to determine in vivo cartilage contact deformation during the stance phase of gait. Throughout the stance phase of gait, the magnitude of peak compartmental contact deformation ranged between 7% and 23% of the resting cartilage thickness and occurred at regions with thicker cartilage. Its excursions in the anteroposterior direction were greater in the medial tibiofemoral compartment as compared to those in the lateral compartment. The contact areas throughout the stance phase were greater in the medial compartment than in the lateral compartment. The information on in vivo tibiofemoral cartilage contact biomechanics during gait could be used to provide physiological boundaries for in vitro testing of cartilage. Also, the data on location and magnitude of deformation among non-diseased knees during gait could identify where loading and later injury might occur in diseased knees. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Liu, Fang; Kozanek, Michal; Hosseini, Ali; Van de Velde, Samuel K.; Gill, Thomas J.; Rubash, Harry E.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Liu, Fang; Kozanek, Michal; Hosseini, Ali; Van de Velde, Samuel K.; Gill, Thomas J.; Rubash, Harry E.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hosseini, Ali] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institute of Health [R01 AR052408, R21 AR051078]; Department of Orthopaedic Surgery at Massachusetts General Hospital FX We would like to gratefully acknowledge the financial support of the National Institute of Health (R01 AR052408, R21 AR051078) and the Department of Orthopaedic Surgery at Massachusetts General Hospital. We would also like to thank the volunteers who participated in this study and Bijoy Thomas for technical assistance. NR 24 TC 56 Z9 56 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD MAR 3 PY 2010 VL 43 IS 4 BP 658 EP 665 DI 10.1016/j.jbiomech.2009.10.028 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 574QW UT WOS:000276008500009 PM 19896131 ER PT J AU Tsika, E Moysidou, M Guo, J Cushman, M Gannon, P Sandaltzopoulos, R Giasson, BI Krainc, D Ischiropoulos, H Mazzulli, JR AF Tsika, Elpida Moysidou, Maria Guo, Jing Cushman, Mimi Gannon, Patrick Sandaltzopoulos, Raphael Giasson, Benoit I. Krainc, Dimitri Ischiropoulos, Harry Mazzulli, Joseph R. TI Distinct Region-Specific alpha-Synuclein Oligomers in A53T Transgenic Mice: Implications for Neurodegeneration SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SPORADIC PARKINSONS-DISEASE; SOLUBLE AMYLOID OLIGOMERS; MULTIPLE SYSTEM ATROPHY; ALZHEIMERS-DISEASE; FIBRIL FORMATION; LEWY BODIES; IN-VITRO; TYROSINE-HYDROXYLASE; SECONDARY STRUCTURE; DOPAMINE AB Aggregation of alpha-synuclein (alpha-syn), a process that generates oligomeric intermediates, is a common pathological feature of several neurodegenerative disorders. Despite the potential importance of the oligomeric alpha-syn intermediates in neuron function, their biochemical properties and pathobiological functions in vivo remain vastly unknown. Here we used two-dimensional analytical separation and an array of biochemical and cell-based assays to characterize alpha-syn oligomers that are present in the nervous system of A53T alpha-syn transgenic mice. The most prominent species identified were 53 angstrom detergent-soluble oligomers, which preceded neurological symptom onset, and were found at equivalent amounts in regions containing alpha-syn inclusions as well as histologically unaffected regions. These oligomers were resistant to SDS, heat, and urea but were sensitive to proteinase-K digestion. Although the oligomers shared similar basic biochemical properties, those obtained from inclusion-bearing regions were prominently reactive to antibodies that recognize oxidized alpha-syn oligomers, significantly accelerated aggregation of alpha-syn in vitro, and caused primary cortical neuron degeneration. In contrast, oligomers obtained from non-inclusion-bearing regions were not toxic and delayed the in vitro formation of alpha-syn fibrils. These data indicate that specific conformations of alpha-syn oligomers are present in distinct brain regions of A53T alpha-syn transgenic mice. The contribution of these oligomers to the development of neuron dysfunction appears to be independent of their absolute quantities and basic biochemical properties but is dictated by the composition and conformation of the intermediates as well as unrecognized brain-region-specific intrinsic factors. C1 [Krainc, Dimitri; Mazzulli, Joseph R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Tsika, Elpida; Moysidou, Maria; Guo, Jing; Cushman, Mimi; Ischiropoulos, Harry; Mazzulli, Joseph R.] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA. [Ischiropoulos, Harry] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Gannon, Patrick; Giasson, Benoit I.; Ischiropoulos, Harry] Univ Penn, Childrens Hosp Philadelphia, Dept Pharmacol, Philadelphia, PA 19104 USA. [Tsika, Elpida; Moysidou, Maria; Sandaltzopoulos, Raphael] Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece. RP Mazzulli, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, CNY Bldg,114 16th St,Neurol 114-2001, Charlestown, MA 02129 USA. EM ischirop@mail.med.upenn.edu; jmazzulli@partners.org FU National Institutes of Health [AG09215, NS053488, R01NS051303]; United States Public Health Service [AG13966]; National Institute of Environmental Health Sciences Center of Excellence in Environmental Toxicology [ES013508]; National Institute of Neurological Disorders and Stroke [F32NS066730] FX This work was supported by the National Institutes of Health Grants AG09215 (B. I. G), NS053488 (B. I. G.), and R01NS051303 (D. K.), United States Public Health Service Grant AG13966 (H. I.), National Institute of Environmental Health Sciences Center of Excellence in Environmental Toxicology Grant ES013508 (H. I), and National Institute of Neurological Disorders and Stroke Award F32NS066730 (J.R.M.). H. I. is the Gisela and Dennis Alter Research Professor of Pediatrics. NR 55 TC 43 Z9 44 U1 0 U2 4 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 MAR 3 PY 2010 VL 30 IS 9 BP 3409 EP 3418 DI 10.1523/JNEUROSCI.4977-09.2010 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 564CS UT WOS:000275191000026 PM 20203200 ER PT J AU Soscia, SJ Kirby, JE Washicosky, KJ Tucker, SM Ingelsson, M Hyman, B Burton, MA Goldstein, LE Duong, S Tanzi, RE Moir, RD AF Soscia, Stephanie J. Kirby, James E. Washicosky, Kevin J. Tucker, Stephanie M. Ingelsson, Martin Hyman, Bradley Burton, Mark A. Goldstein, Lee E. Duong, Scott Tanzi, Rudolph E. Moir, Robert D. TI The Alzheimer's Disease-Associated Amyloid beta-Protein Is an Antimicrobial Peptide SO PLOS ONE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; PRECURSOR-LIKE PROTEIN; A-BETA; INNATE IMMUNITY; CELL-DEATH; APOLIPOPROTEIN-E; FAMILY-MEMBERS; ALAMAR-BLUE; BRAIN; LL-37 AB Background: The amyloid beta-protein (A beta) is believed to be the key mediator of Alzheimer's disease (AD) pathology. A beta is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, A beta has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities. Methodology/Principal Findings: Here, we provide data supporting an in vivo function for A beta as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of A beta and LL-37, an archetypical human AMP. Findings reveal that A beta exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue A beta levels. Consistent with A beta-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-A beta antibodies. Conclusions/Significance: Our findings suggest A beta is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of A beta-mediated pathology and has important implications for ongoing and future AD treatment strategies. C1 [Soscia, Stephanie J.; Washicosky, Kevin J.; Tucker, Stephanie M.; Hyman, Bradley; Tanzi, Rudolph E.; Moir, Robert D.] Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA USA. [Soscia, Stephanie J.; Washicosky, Kevin J.; Tucker, Stephanie M.; Hyman, Bradley; Tanzi, Rudolph E.; Moir, Robert D.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Soscia, Stephanie J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Kirby, James E.; Duong, Scott] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Ingelsson, Martin] Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala, Sweden. [Hyman, Bradley; Tanzi, Rudolph E.; Moir, Robert D.] Harvard Univ, Sch Med, Boston, MA USA. [Burton, Mark A.; Goldstein, Lee E.] Boston Univ, Sch Med, Coll Engn, Mol Aging & Dev Lab,Photon Ctr, Boston, MA 02118 USA. [Burton, Mark A.; Goldstein, Lee E.] Boston Univ, Alzheimers Dis Ctr, Boston, MA 02118 USA. RP Soscia, SJ (reprint author), Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA USA. EM tanzi@helix.mgh.harvard.edu OI Goldstein, Lee/0000-0001-8419-9800 FU Cure Alzheimer's Disease Fund FX This work was supported by grants from the Cure Alzheimer's Disease Fund (http://www.curealzfund.org/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 85 TC 234 Z9 239 U1 10 U2 54 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 MAR 3 PY 2010 VL 5 IS 3 AR e9505 DI 10.1371/journal.pone.0009505 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 562OZ UT WOS:000275063400012 PM 20209079 ER PT J AU Yao, JK Dougherty, GG Reddy, RD Keshavan, MS Montrose, DM Matson, WR McEvoy, J Kaddurah-Daouk, R AF Yao, Jeffrey K. Dougherty, George G., Jr. Reddy, Ravinder D. Keshavan, Matcheri S. Montrose, Debra M. Matson, Wayne R. McEvoy, Joseph Kaddurah-Daouk, Rima TI Homeostatic Imbalance of Purine Catabolism in First-Episode Neuroleptic-Naive Patients with Schizophrenia SO PLOS ONE LA English DT Article ID SERUM URIC-ACID; PERFORMANCE LIQUID-CHROMATOGRAPHY; IMPAIRED GLUTATHIONE SYNTHESIS; MULTIPLE-SCLEROSIS PATIENTS; PLASMA ANTIOXIDANTS; PARKINSONS-DISEASE; OXIDATIVE STRESS; RISK-FACTOR; SYSTEM; BRAIN AB Background: Purine catabolism may be an unappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. Accumulating evidence suggests a pivotal role of oxidative stress in schizophrenia pathology. Methodology/Principal Findings: Using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system, we compared 6 purine metabolites simultaneously in plasma between first-episode neuroleptic-naive patients with schizophrenia (FENNS, n = 25) and healthy controls (HC, n = 30), as well as between FENNS at baseline (BL) and 4 weeks (4w) after antipsychotic treatment. Significantly higher levels of xanthosine (Xant) and lower levels of guanine (G) were seen in both patient groups compared to HC subjects. Moreover, the ratios of G/guanosine (Gr), uric acid (UA)/Gr, and UA/Xant were significantly lower, whereas the ratio of Xant/G was significantly higher in FENNS-BL than in HC. Such changes remained in FENNS-4w with exception that the ratio of UA/Gr was normalized. All 3 groups had significant correlations between G and UA, and Xan and hypoxanthine (Hx). By contrast, correlations of UA with each of Xan and Hx, and the correlation of Xan with Gr were all quite significant for the HC but not for the FENNS. Finally, correlations of Gr with each of UA and G were significant for both HC and FENNS-BL but not for the FENNS-4w. Conclusions/Significance: During purine catabolism, both conversions of Gr to G and of Xant to Xan are reversible. Decreased ratios of product to precursor suggested a shift favorable to Xant production from Xan, resulting in decreased UA levels in the FENNS. Specifically, the reduced UA/Gr ratio was nearly normalized after 4 weeks of antipsychotic treatment. In addition, there are tightly correlated precursor and product relationships within purine pathways; although some of these correlations persist across disease or medication status, others appear to be lost among FENNS. Taken together, these results suggest that the potential for steady formation of antioxidant UA from purine catabolism is altered early in the course of illness. C1 [Yao, Jeffrey K.; Dougherty, George G., Jr.; Reddy, Ravinder D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Yao, Jeffrey K.; Dougherty, George G., Jr.; Reddy, Ravinder D.; Keshavan, Matcheri S.; Montrose, Debra M.] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. [Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Keshavan, Matcheri S.] Harvard Univ, Boston, MA 02115 USA. [Matson, Wayne R.] Bedford VA Med Ctr, Bedford, MA USA. [McEvoy, Joseph; Kaddurah-Daouk, Rima] Duke Univ, Med Ctr, Durham, NC USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM jkyao@pitt.edu FU Department of Veterans Affairs (VA); Veterans Health Administration; Office of Research and Development; Biomedical Laboratory Research Development; VA Pittsburgh Healthcare System; National Institute of Health [MH58141, MH64118, MH45203, R24 GM078233, c UL1 RR024153]; NIH/NCRR/GCRC [M01 RR00056]; Metabolomics Research Network (RKD); Stanley Medical Research Institute (RKD); National Alliance for Research on Schizophrenia and Affective Disorders (RKD) FX This material is based upon work supported in part by the grants from the Department of Veterans Affairs (VA), Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research & Development [Merit Reviews (JKY) and Senior Research Career Scientist Award (JKY)], VA Pittsburgh Healthcare System (JKY, GGD, RDR), National Institute of Health [MH58141 (JKY), MH64118 (RDR), MH45203 (MSK), R24 GM078233 (RKD), c UL1 RR024153 and NIH/NCRR/GCRC Grant M01 RR00056], Metabolomics Research Network (RKD); Stanley Medical Research Institute (RKD), and National Alliance for Research on Schizophrenia and Affective Disorders (RKD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 83 TC 31 Z9 31 U1 0 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 MAR 3 PY 2010 VL 5 IS 3 AR e9508 DI 10.1371/journal.pone.0009508 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 562OZ UT WOS:000275063400014 PM 20209081 ER PT J AU Villar, J Cabrera, NE Casula, M Flores, C Valladares, F Diaz-Flores, L Muros, M Slutsky, AS Kacmarek, RM AF Villar, Jesus Cabrera, Nuria E. Casula, Milena Flores, Carlos Valladares, Francisco Diaz-Flores, Lucio Muros, Mercedes Slutsky, Arthur S. Kacmarek, Robert M. TI Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious, ventilator-induced lung injury model SO RESPIRATORY RESEARCH LA English DT Article ID END-EXPIRATORY PRESSURE; TOLL-LIKE RECEPTORS; RESPIRATORY-DISTRESS-SYNDROME; INFLAMMATORY RESPONSE; TIDAL-VOLUME; KAPPA-B; NEGATIVE REGULATOR; CYTOKINE RELEASE; EPITHELIAL-CELLS; IN-VITRO AB Background: Previous experimental studies have shown that injurious mechanical ventilation has a direct effect on pulmonary and systemic immune responses. How these responses are propagated or attenuated is a matter of speculation. The goal of this study was to determine the contribution of mechanical ventilation in the regulation of Toll-like receptor (TLR) signaling and interleukin-1 receptor associated kinase-3 (IRAK-3) during experimental ventilator-induced lung injury. Methods: Prospective, randomized, controlled animal study using male, healthy adults Sprague-Dawley rats weighing 300-350 g. Animals were anesthetized and randomized to spontaneous breathing and to two different mechanical ventilation strategies for 4 hours: high tidal volume (V(T)) ( 20 ml/kg) and low VT (6 ml/kg). Histological evaluation, TLR2, TLR4, IRAK3 gene expression, IRAK-3 protein levels, inhibitory kappa B alpha (I kappa B alpha), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL6) gene expression in the lungs and TNF-alpha and IL-6 protein serum concentrations were analyzed. Results: High VT mechanical ventilation for 4 hours was associated with a significant increase of TLR4 but not TLR2, a significant decrease of IRAK3 lung gene expression and protein levels, a significant decrease of I kappa Ba, and a higher lung expression and serum concentrations of pro-inflammatory cytokines. Conclusions: The current study supports an interaction between TLR4 and IRAK-3 signaling pathway for the overexpression and release of pro-inflammatory cytokines during ventilator-induced lung injury. Our study also suggests that injurious mechanical ventilation may elicit an immune response that is similar to that observed during infections. C1 [Villar, Jesus; Cabrera, Nuria E.; Casula, Milena; Flores, Carlos; Valladares, Francisco; Muros, Mercedes] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus; Cabrera, Nuria E.; Casula, Milena] Hosp Univ Dr Negrin, Res Unit, MODERN, Las Palmas Gran Canaria, Spain. [Villar, Jesus; Slutsky, Arthur S.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Flores, Carlos] Hosp Univ NS de Candelaria, Res Unit, Tenerife, Spain. [Valladares, Francisco; Diaz-Flores, Lucio] Univ La Laguna, Dept Anat Pathol & Histol, Tenerife, Spain. [Muros, Mercedes] Hosp Univ NS de Candelaria, Dept Clin Biochem, Tenerife, Spain. [Slutsky, Arthur S.] Univ Toronto, Interdepartmental Div Crit Care Med, Toronto, ON, Canada. [Slutsky, Arthur S.] King Saud Univ, Riyadh, Saudi Arabia. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Villar, J (reprint author), Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. EM jesus.villar54@gmail.com FU Ministerio de Ciencia of Spain [SAF 2004-06833]; FUNCIS [53/04]; Instituto de Salud Carlos III and FUNCIS [EMER07/001]; ENCYT FX The study has been supported by grants from Ministerio de Ciencia of Spain (SAF 2004-06833), FUNCIS (53/04), and by a specific agreement between Instituto de Salud Carlos III and FUNCIS (EMER07/001) under the ENCYT 2015 framework. NR 44 TC 26 Z9 30 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-9921 J9 RESP RES JI Respir. Res. PD MAR 3 PY 2010 VL 11 AR 27 DI 10.1186/1465-9921-11-27 PG 11 WC Respiratory System SC Respiratory System GA 571RK UT WOS:000275772200001 PM 20199666 ER PT J AU Baggish, AL Hutter, AM Wang, F Yared, K Weiner, RB Kupperman, E Picard, MH Wood, MJ AF Baggish, Aaron L. Hutter, Adolph M., Jr. Wang, Francis Yared, Kibar Weiner, Rory B. Kupperman, Eli Picard, Michael H. Wood, Malissa J. TI Cardiovascular Screening in College Athletes With and Without Electrocardiography A Cross-sectional Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID SUDDEN CARDIAC DEATH; EUROPEAN-SOCIETY; CLINICAL-SIGNIFICANCE; OF-CARDIOLOGY; RECOMMENDATIONS; DISEASE; ABNORMALITIES; HEART AB Background: Although cardiovascular screening is recommended for athletes before participating in sports, the role of 12-lead electrocardiography (ECG) remains uncertain. To date, no prospective data that compare screening with and without ECG have been available. Objective: To compare the performance of preparticipation screening limited to medical history and physical examination with a strategy that integrates these with ECG. Design: Cross-sectional comparison of screening strategies. Setting: University Health Services, Harvard University, Cambridge, Massachusetts. Participants: 510 collegiate athletes who received cardiovascular screening before athletic participation. Measurements: Each participant had routine history and examination limited screening and ECG. They received transthoracic echocardiography (TTE) to detect or exclude cardiac findings with relevance to sports participation. The performance of screening with history and examination only was compared with that of screening that integrated history, examination, and ECG. Results: Cardiac abnormalities with relevance to sports participation risk were observed on TTE in 11 of 510 participants (prevalence, 2.2%). Screening with history and examination alone detected abnormalities in 5 of these 11 athletes (sensitivity, 45.5% [95% CI, 16.8% to 76.2%]; specificity, 94.4% [CI, 92.0% to 96.2%]). Electrocardiography detected 5 additional participants with cardiac abnormalities (for a total of 10 of 11 participants), thereby improving the overall sensitivity of screening to 90.9% (CI, 58.7% to 99.8%). However, including ECG reduced the specificity of screening to 82.7% (CI, 79.1% to 86.0%) and was associated with a false-positive rate of 16.9% (vs. 5.5% for screening with history and examination only). Limitation: Definitive conclusions regarding the effect of ECG inclusion on sudden death rates cannot be made. Conclusion: Adding ECG to medical history and physical examination improves the overall sensitivity of preparticipation cardiovascular screening in athletes. However, this strategy is associated with an increased rate of false-positive results when current ECG interpretation criteria are used. C1 [Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 24 TC 152 Z9 154 U1 0 U2 16 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 MAR 2 PY 2010 VL 152 IS 5 BP 269 EP W79 DI 10.7326/0003-4819-152-5-201003020-00004 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 565XJ UT WOS:000275329600001 PM 20194232 ER PT J AU Goldstein, N Carlson, M Livote, E Kutner, JS AF Goldstein, Nathan Carlson, Melissa Livote, Elayne Kutner, Jean S. TI Brief Communication: Management of Implantable Cardioverter-Defibrillators in Hospice: A Nationwide Survey SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID OF-LIFE; CARE; END AB Background: Communication about the deactivation of implantable cardioverter-defibrillators (ICDs) in patients near the end of life is rare. Objective: To determine whether hospices are admitting patients with ICDs, whether such patients are receiving shocks, and how hospices manage ICDs. Design: Cross-sectional survey. Setting: Randomly selected hospice facilities. Participants: 900 hospices, 414 of which responded fully. Measurements: Frequency of admission of patients with ICDs, frequency with which patients received shocks, existence of ICD deactivation policies, and frequency of deactivation. Results: 97% of hospices admitted patients with ICDs, and 58% reported that in the past year, a patient had been shocked. Only 10% of hospices had a policy that addressed deactivation. On average, 42% (95% CI, 37% to 48%) of patients with ICDs had the shocking function deactivated. Limitation: The study relied on the knowledge of hospice administrators. Conclusion: Hospices are admitting patients with ICDs, and patients are being shocked at the end of life. Ensuring that hospices have policies in place to address deactivation may improve the care for patients with these devices. The authors provide a sample deactivation policy (available at www.annals.org). C1 [Goldstein, Nathan] Mt Sinai Sch Med, Dept Geriatr, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Bronx, NY USA. Univ Colorado, Denver Sch Med, Aurora, CO USA. RP Goldstein, N (reprint author), Mt Sinai Sch Med, Dept Geriatr, Box 1070,1 Gustave Levy Pl, New York, NY 10029 USA. EM Nathan.Goldstein@mssm.edu FU National Institute of Aging [K23 AG025933K07AG030337-01A2]; National Institute of Nursing Research [1K99NR010495-01] FX By the National Institute of Aging, grants K23 AG025933 (Dr. Goldstein) and K07AG030337-01A2 (Dr. Kutner), and the National Institute of Nursing Research, grant 1K99NR010495-01 (Dr. Carlson). NR 14 TC 56 Z9 56 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 MAR 2 PY 2010 VL 152 IS 5 BP 296 EP W94 DI 10.7326/0003-4819-152-5-201003020-00007 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 565XJ UT WOS:000275329600004 PM 20194235 ER PT J AU Vetter, ML Iqbal, N Dalton-Bakes, C Volger, S Wadden, TA AF Vetter, Marion L. Iqbal, Nayyar Dalton-Bakes, Cornelia Volger, Sheri Wadden, Thomas A. TI Long-Term Effects of Low-Carbohydrate Versus Low-Fat Diets in Obese Persons SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID WEIGHT-LOSS DIETS C1 [Vetter, Marion L.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Iqbal, Nayyar; Dalton-Bakes, Cornelia] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Volger, Sheri; Wadden, Thomas A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Vetter, ML (reprint author), Hosp Univ Penn, 3400 Spruce St, Philadelphia, PA 19104 USA. OI volger, sheri/0000-0002-1689-1173 NR 3 TC 6 Z9 6 U1 0 U2 3 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 MAR 2 PY 2010 VL 152 IS 5 BP 334 EP 335 DI 10.7326/0003-4819-152-5-201003020-00020 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 565XJ UT WOS:000275329600016 PM 20194246 ER PT J AU Punglia, RS Saito, AM Neville, BA Earle, CC Weeks, JC AF Punglia, Rinaa S. Saito, Akiko M. Neville, Bridget A. Earle, Craig C. Weeks, Jane C. TI Impact of interval from breast conserving surgery to radiotherapy on local recurrence in older women with breast cancer: retrospective cohort analysis SO BRITISH MEDICAL JOURNAL LA English DT Article ID RADIATION-THERAPY; CONSERVATIVE SURGERY; RANDOMIZED-TRIALS; COMORBIDITY INDEX; 15-YEAR SURVIVAL; CHEMOTHERAPY; POPULATION; CARCINOMA; OUTCOMES; TIME AB Objectives To determine if the length of interval between breast conserving surgery and start of radiotherapy affects local recurrence and to identify factors that might be associated with delay in older women with breast cancer. Design Retrospective cohort analysis with Cox proportional hazards models to study the association between time to radiotherapy and local recurrence, and propensity score and instrumental variable analyses to confirm findings. Logistic regression investigated factors associated with later start of radiotherapy. Setting Linked database ( Surveillance, Epidemiology, and End Results Program-Medicare) in the United States Participants 18 050 women aged over 65 with stage 0-II breast cancer diagnosed in 1991-2002 who received breast conserving surgery and radiotherapy but not chemotherapy. Main outcome measure Local recurrence. Results Median time from surgery to start of radiotherapy was 34 days, with 29.9% (n=5389) of women starting radiotherapy after six weeks. Just over 4% (n=734) of the cohort experienced a local recurrence. After adjustment for clinical and sociodemographic factors, intervals over six weeks were associated with increased likelihood of local recurrence (hazard ratio 1.19, 95% confidence interval 1.01 to 1.39, P=0.033). When the interval was modelled continuously ( assessing accumulation of risk by day), the effect was statistically stronger ( hazard ratio 1.005 per day, 1.002 to 1.008, P=0.004). Propensity score and instrumental variable analysis confirmed these findings. Instrumental variable analysis showed that intervals over six weeks were associated with a 0.96% increase in recurrence at five years (P=0.026). In multivariable analysis, starting radiotherapy after six weeks was significantly associated with positive nodes, comorbidity, history of low income, Hispanic ethnicity, non-white race, later year of diagnosis, and residence outside the southern states of the US. Conclusions There is a continuous relation between the interval from breast conserving surgery to radiotherapy and local recurrence in older women with breast cancer, suggesting that starting radiotherapy as soon as possible could minimise the risk of local recurrence. There are considerable disparities in time to starting radiotherapy after breast conserving surgery. Regions of the US known to have increased rates of breast conserving surgery had longer intervals before radiotherapy, suggesting limitations in capacity. Given the known negative impact of local recurrence on survival, mechanisms to ameliorate disparities and policies regarding waiting times for treatment might be warranted. C1 [Punglia, Rinaa S.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Neville, Bridget A.; Earle, Craig C.; Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Saito, Akiko M.] Natl Hosp Org Nagoya Med Ctr, Clin Res Ctr, Lab Clin Epidemiol & Hlth Serv Res, Aichi, Japan. [Earle, Craig C.] Inst Clin Evaluat Sci, Toronto, ON, Canada. RP Punglia, RS (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM rpunglia@lroc.harvard.edu FU National Institutes of Health [1K07 CA118629]; American Society of Clinical Oncology FX This study was supported in part by a grant from the National Institutes of Health (1K07 CA118629 to RSP) and from the American Society of Clinical Oncology (Career Development Award to RSP). It was first presented in part at the annual meeting of the American Society of Clinical Oncology, June 2008. NR 35 TC 32 Z9 34 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD MAR 2 PY 2010 VL 340 AR c845 DI 10.1136/bmj.c845 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 565FI UT WOS:000275274300024 PM 20197326 ER PT J AU Vandebroek, I Balick, MJ Ososki, A Kronenberg, F Yukes, J Wade, C Jimenez, F Peguero, B Castillo, D AF Vandebroek, Ina Balick, Michael J. Ososki, Andreana Kronenberg, Fredi Yukes, Jolene Wade, Christine Jimenez, Francisco Peguero, Brigido Castillo, Daisy TI The importance of botellas and other plant mixtures in Dominican traditional medicine SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Ethnobotany; Ethnomedicine; Plant mixtures; Herbal remedies; Dominican Republic; Migrants; New York City; Caribbean; Botella; Cultural keystone practice ID NEW-YORK-CITY; WOMENS HEALTH CONDITIONS; LATINO HEALERS; BOTANICAS; ETHNOBOTANY AB Ethnopharmacological relevance: Plant mixtures are understudied in ethnobotanical research. Aim of the study: To investigate the importance of plant mixtures (remedies consisting of at least two plants) in Dominican traditional medicine. Materials and methods: A Spanish language questionnaire was administered to 174 Dominicans living in New York City (NYC) and 145 Dominicans living in the Dominican Republic (DR), including lay persons (who self-medicate with plants) and specialists (traditional healers). Plants were identified through specimens purchased in NYC botanica shops and Latino grocery shops, and from voucher collections. Results: The percentage of mixtures as compared to single plants in plant use reports varied between 32 and 41%, depending on the geographic location (NYC or DR) and participant status (lay person or specialist). Respiratory conditions, reproductive health and genitourinary conditions were the main categories for which Dominicans use plant mixtures. Lay persons reported significantly more mixtures prepared as teas, mainly used in NYC to treat respiratory conditions. Specialists mentioned significantly more botellas (bottled herbal mixtures), used most frequently in the DR to treat reproductive health and genitourinary conditions. Cluster analysis demonstrated that different plant species are used to treat respiratory conditions as compared to reproductive health and genitourinary conditions. Interview participants believed that combining plants in mixtures increases their potency and versatility as medicines. Conclusions: The present study demonstrates the importance and complexity of plant mixtures in Dominican traditional medicine and the variation in its practices influenced by migration from the DR to NYC, shedding new lighten the foundations of a particular ethnomedical system. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Vandebroek, Ina; Balick, Michael J.; Kronenberg, Fredi; Yukes, Jolene] New York Bot Garden, Inst Econ Bot, Bronx, NY 10458 USA. [Ososki, Andreana] San Francisco VA Med Ctr, San Francisco, CA USA. [Wade, Christine] CUNY, Off Inst Res & Assessment, New York, NY 10021 USA. [Jimenez, Francisco; Peguero, Brigido; Castillo, Daisy] Jardin Bot Nacl Dr Rafael Ma Moscoso, Dept Bot, Santo Domingo, Dominican Rep. RP Vandebroek, I (reprint author), New York Bot Garden, Inst Econ Bot, 2900 So Blvd, Bronx, NY 10458 USA. EM ivandebroek@nybg.org FU National Institutes of Health/National Center for Complementary and Alternative Medicine [5 R21 AT 001889-02] FX The authors wish to thank Dominican interview participants in New York City and the Dominican Republic for generously sharing their knowledge about traditional medicine. This project was supported by a grant from the National Institutes of Health/National Center for Complementary and Alternative Medicine (PI: Dr. Michael J. Balick, Grant # 5 R21 AT 001889-02). Hannah Stevens, MA., Manager of the NYBG GIS laboratory is kindly thanked for elaborating maps of the study sites. Irina Adam took the picture of the Dominican botella. We are indebted to interns and research assistants at the Institute of Economic Botany of The New York Botanical Garden who collaborated in this project (Gabriela Alvarez, Frans Beltran, Levenia Duran, Daniel Kulakowski, Greta Meyers, Saneddy Quezada, Sam Stein, Margaret Terrero) and volunteers (Yadira Arias, Tomas Diaz, Ashley Duval, Claudia Remes). We would also like to thank Dr. Linda Cushman, Ms. Iris De Castro, Dr. Flor Henderson, Rafael Lantigua MD, Dr. Milciades Mejia, Ms. Miriam Mejia, and Lionel Robineau MD for their help with the project. NR 33 TC 25 Z9 25 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD MAR 2 PY 2010 VL 128 IS 1 BP 20 EP 41 DI 10.1016/j.jep.2009.12.013 PG 22 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 574RI UT WOS:000276010000003 PM 20006697 ER PT J AU Maloney, JD Maloney, JD AF Maloney, James D. Maloney, James D., III TI Vegetation Size Marker for Extraction Technique? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE lead extraction; percutaneous endocarditis; intracardiac vegetations ID INFECTIVE ENDOCARDITIS; PACEMAKER ENDOCARDITIS; SURGICAL EXTRACTION; LEAD EXTRACTION; MANAGEMENT; DIAGNOSIS; RISK C1 [Maloney, James D.] Heartland Spine & Specialty Hosp, Cardiovasc Serv, Overland Pk, KS USA. [Maloney, James D., III] Univ Wisconsin, Dept Cardiothorac Surg, Madison, WI USA. [Maloney, James D., III] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Thorac Surg Sect, Madison, WI 53792 USA. RP Maloney, JD (reprint author), Carondelet Heart Inst, 1000 Carondelet Dr, Kansas City, MO 64114 USA. EM jdmepmd@aol.com; jdmepmd@aol.com NR 20 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 2 PY 2010 VL 55 IS 9 BP 895 EP 897 DI 10.1016/j.jacc.2009.11.035 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 559XS UT WOS:000274865100008 PM 20185040 ER PT J AU Shi, JR Guan, J Jiang, BB Brenner, DA del Monte, F Ward, JE Connors, LH Sawyer, DB Semigran, MJ Macgillivray, TE Seldin, DC Falk, R Liao, R AF Shi, Jianru Guan, Jian Jiang, Bingbing Brenner, Daniel A. del Monte, Federica Ward, Jennifer E. Connors, Lawreen H. Sawyer, Douglas B. Semigran, Marc J. Macgillivray, Thomas E. Seldin, David C. Falk, Rodney Liao, Ronglih TI Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38 alpha MAPK pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amyloid; cell death; heart failure; TAB1; reactive oxygen species ID ACTIVATED PROTEIN-KINASE; ALZHEIMERS-DISEASE; INDEPENDENT ACTIVATION; P38 KINASE; STRESS; HEART; TAB1; MECHANISMS; RECEPTOR AB Patients with primary (AL) cardiac amyloidosis suffer from progressive cardiomyopathy with a median survival of less than 8 months and a 5-year survival of <10%. Contributing to this poor prognosis is the fact that these patients generally do not tolerate standard heart failure therapies. The molecular mechanisms underlying this deadly form of heart disease remain unclear. Although interstitial amyloid fibril deposition of Ig light chain proteins is a major cause of cardiac dysfunction in AL cardiac amyloidosis, we have previously shown that amyloid precursor proteins directly impair cardiac function at the cellular and isolated organ levels, independent of fibril formation. In this study, we report that amyloidogenic light chain (AL-LC) proteins provoke oxidative stress, cellular dysfunction, and apoptosis in isolated adult cardiomyocytes through activation of p38 mitogen-activated protein kinase (MAPK). AL-LC-induced p38 activation was found to be independent of the upstream MAPK kinase, MKK3/6, and instead depends upon transforming growth factor-beta-activated protein kinase-1 binding protein-1 (TAB1)-mediated p38 alpha MAPK autophosphorylation. Treatment of cardiomyocytes with SB203580, a selective p38 MAPK inhibitor, significantly attenuated AL-LC-induced oxidative stress, cellular dysfunction, and apoptosis. Our data provide a unique mechanistic insight into the pathogenesis of AL-LC cardiac toxicity and suggest that TAB1-mediated p38 alpha MAPK autophosphorylation may serve as an important event leading to cardiac dysfunction and subsequent heart failure. C1 [Shi, Jianru; Guan, Jian; Jiang, Bingbing; Brenner, Daniel A.; Liao, Ronglih] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiac Muscle Res Lab,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Guan, Jian; Seldin, David C.; Liao, Ronglih] Boston Univ, Sch Med, Mol Med Grad Program, Boston, MA 02118 USA. [Ward, Jennifer E.; Connors, Lawreen H.; Seldin, David C.] Boston Univ, Sch Med, Amyloid Treatment & Res Program, Boston, MA 02118 USA. [del Monte, Federica] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [del Monte, Federica] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Sawyer, Douglas B.] Vanderbilt Univ, Dept Med, Sch Med, Div Cardiovasc Med, Nashville, TN 37232 USA. [Semigran, Marc J.] Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. [Macgillivray, Thomas E.] Massachusetts Gen Hosp, Cardiac Surg Div, Boston, MA 02114 USA. [Falk, Rodney] Harvard Vanguard Med Associates, Boston, MA 02116 USA. RP Liao, R (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiac Muscle Res Lab,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. EM rliao@rics.bwh.harvard.edu OI Ward, Jennifer/0000-0003-0158-9091; Connors, Lawreen/0000-0002-4672-4296 FU National Institutes of Health [HL088533, HL071775, HL093148, HL086967, HL68705]; Gerry Amyloid Foundation; Amyloid Research Fund; American Heart Association FX We thank Dr. Yibin Wang for his generosity in providing reagents, DNp38 alpha TG mice, and critical scientific discussion. The authors thank Drs. Judith Gwathmey and William Dec for their generosity in providing human heart samples and helpful discussions. We thank Dr. Bo Wang and Mr. Soeun Ngoy for excellent technical support in adult cardiomyocyte isolation and osmotic pump implantation, respectively. This work was supported in part by funding from National Institutes of Health Grants HL088533, HL071775, HL093148 ( to R. L.), HL086967, and HL68705 ( to D. C. S.), as well as the Gerry Amyloid Foundation and Amyloid Research Fund at Boston University ( L. H. C. and D. C. S.). J.S. was supported by American Heart Association NE affiliate postdoctoral fellowship award. NR 27 TC 92 Z9 100 U1 0 U2 12 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 MAR 2 PY 2010 VL 107 IS 9 BP 4188 EP 4193 DI 10.1073/pnas.0912263107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 563KP UT WOS:000275131100045 PM 20150510 ER PT J AU Gethin-Jones, TL Evans, NR Morse, CR AF Gethin-Jones, Thomas L. Evans, Nathaniel R., III Morse, Christopher R. TI Surgical management of mediastinal liposarcoma extending from hypopharynx to carina: Case report SO WORLD JOURNAL OF SURGICAL ONCOLOGY LA English DT Article AB We describe the complete resection of a giant, well-differentiated mediastinal liposarcoma extending retropharynx to envelop the aortic arch, trachea and esophagus following preoperative radiotherapy. C1 [Gethin-Jones, Thomas L.; Evans, Nathaniel R., III; Morse, Christopher R.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Morse, CR (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM crmorse@partners.org RI Evans, Nathaniel/I-2255-2013 OI Evans, Nathaniel/0000-0001-5767-6907 NR 5 TC 3 Z9 3 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7819 J9 WORLD J SURG ONCOL JI World J. Surg. Oncol. PD MAR 2 PY 2010 VL 8 AR 13 DI 10.1186/1477-7819-8-13 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 571TP UT WOS:000275779000001 PM 20196857 ER PT J AU Azar, AR Chopra, MP Cho, LY Coakley, EH Rudolph, JL AF Azar, Armin R. Chopra, Mohit P. Cho, Lydia Y. Coakley, Eugenie H. Rudolph, James L. TI Remission in Major Depression: Results from a Geriatric Primary Care Population SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 05-08, 2010 CL Savannah, GA SP Amer Assoc Geriat Psychiat C1 [Azar, Armin R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chopra, Mohit P.; Cho, Lydia Y.; Rudolph, James L.] VA Boston Healthcare Syst, Boston, MA USA. [Coakley, Eugenie H.] John Snow Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2010 VL 18 IS 3 SU 1 BP S59 EP S60 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 753PB UT WOS:000289790800061 ER PT J AU Cohen, CI Kasckow, J Jeste, DV Vahia, I AF Cohen, Carl I. Kasckow, John Jeste, Dilip V. Vahia, Ipsit TI SUICIDAL BEHAVIOR IN THE OLDER PATIENT WITH SCHIZOPHRENIA SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 05-08, 2010 CL Savannah, GA SP Amer Assoc Geriat Psychiat C1 [Kasckow, John] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Jeste, Dilip V.; Vahia, Ipsit] Univ Calif San Diego, San Diego, CA 92103 USA. [Cohen, Carl I.] Suny Downstate Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2010 VL 18 IS 3 SU 1 BP S42 EP S43 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 753PB UT WOS:000289790800051 ER PT J AU Mavandadi, S Sayers, SL Oslin, DW AF Mavandadi, Shahrzad Sayers, Steven L. Oslin, David W. TI Social Exchanges and Suicide Ideation among Older Veterans with Behavioral Health Issues SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 05-08, 2010 CL Savannah, GA SP Amer Assoc Geriat Psychiat C1 [Mavandadi, Shahrzad; Sayers, Steven L.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Oslin, David W.] Univ Penn, Philadelphia, PA 19104 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 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2010 VL 18 IS 3 SU 1 BP S56 EP S56 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 753PB UT WOS:000289790800055 ER PT J AU Peskind, ER Li, G Millard, S Chi, PB Sokal, I Yu, CE Bekris, LM Raskind, M Galasko, D Montine, TJ AF Peskind, Elaine R. Li, Gail Millard, Steven Chi, Peter B. Sokal, Izabela Yu, Chang-En Bekris, Lynn M. Raskind, Murray Galasko, Douglas Montine, Thomas J. TI Age-related Decline in Cognitive Function is Associated with Cerebrospinal Fluid Concentration of Brain-Derived Neurotrophic Factor SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 05-08, 2010 CL Savannah, GA SP Amer Assoc Geriat Psychiat C1 [Peskind, Elaine R.; Li, Gail; Millard, Steven; Raskind, Murray] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Chi, Peter B.; Sokal, Izabela; Yu, Chang-En; Bekris, Lynn M.; Montine, Thomas J.] Univ Washington, Seattle, WA 98195 USA. [Galasko, Douglas] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2010 VL 18 IS 3 SU 1 BP S70 EP S71 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 753PB UT WOS:000289790800078 ER PT J AU Raskind, M Wang, LY Wilkinson, CW Li, G Sikkema, CL Millard, S Hanscom, B Galasko, D Peskind, ER AF Raskind, Murray Wang, Lucy Y. Wilkinson, Charles W. Li, Gail Sikkema, Carl L. Millard, Steven Hanscom, Brett Galasko, Douglas Peskind, Elaine R. TI Cerebrospinal Fluid Norepinephrine is Inversely Related to Aspects of Cognition in Brain Aging SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 05-08, 2010 CL Savannah, GA SP Amer Assoc Geriat Psychiat C1 [Raskind, Murray; Wang, Lucy Y.; Wilkinson, Charles W.; Li, Gail; Sikkema, Carl L.; Millard, Steven; Peskind, Elaine R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Hanscom, Brett] Univ Washington, Seattle, WA 98195 USA. [Galasko, Douglas] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2010 VL 18 IS 3 SU 1 BP S70 EP S70 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 753PB UT WOS:000289790800077 ER PT J AU Sultzer, D Melrose, R Campa, OM Achamallah, N Harwood, D Brody, A Walston, A Mandelkern, M AF Sultzer, David Melrose, Rebecca Campa, Olivia M. Achamallah, Natalie Harwood, Dylan Brody, Arthur Walston, Amy Mandelkern, Mark TI Cholinergic Receptor Imaging in Alzheimer's Disease: Method and Early Results SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 05-08, 2010 CL Savannah, GA SP Amer Assoc Geriat Psychiat C1 [Melrose, Rebecca; Campa, Olivia M.; Achamallah, Natalie; Harwood, Dylan; Brody, Arthur; Walston, Amy] VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA USA. [Mandelkern, Mark] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv, Los Angeles, CA USA. [Sultzer, David] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAR PY 2010 VL 18 IS 3 SU 1 BP S71 EP S72 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 753PB UT WOS:000289790800079 ER PT J AU Marill, KA deSouza, IS Nishijima, DK Senecal, EL Setnik, GS Stair, TO Ruskin, JN Ellinor, PT AF Marill, Keith A. deSouza, Ian S. Nishijima, Daniel K. Senecal, Emily L. Setnik, Gary S. Stair, Thomas O. Ruskin, Jeremy N. Ellinor, Patrick T. TI Amiodarone or Procainamide for the Termination of Sustained Stable Ventricular Tachycardia: An Historical Multicenter Comparison SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE tachycardia; ventricular; amiodarone; procainamide ID WIDE QRS COMPLEX; INTRAVENOUS AMIODARONE; INTRAVENTRICULAR-CONDUCTION; DIFFERENTIAL-DIAGNOSIS; REFRACTORINESS; INDUCTION; LIDOCAINE; EFFICACY; SAFETY AB Objectives: The objective was to compare the effectiveness of intravenous (IV) procainamide and amiodarone for the termination of spontaneous stable sustained ventricular tachycardia (VT). Methods: A historical cohort study of consecutive adult patients with stable sustained VT treated with IV amiodarone or procainamide was performed at four urban hospitals. Patients were identified for enrollment by admissions for VT and treatment with the study agents in the emergency department (ED) from 1993 to 2008. The primary measured outcome was VT termination within 20 minutes of onset of study medicine infusion. A secondary effectiveness outcome was the ultimate need for electrical therapy to terminate the VT episode. Major adverse effects were tabulated, and blood pressure responses to medication infusions were compared. Results: There were 97 infusions of amiodarone or procainamide in 90 patients with VT, but the primary outcome was unknown after 14 infusions due to administration of another antidysrhythmic during the 20-minute observation period. The rates of VT termination were 25% (13/53) and 30% (9/30) for amiodarone and procainamide, respectively. The adjusted odds of termination with procainamide compared to amiodarone was 1.2 (95% confidence interval [CI] = 0.4 to 3.9). Ultimately, 35/66 amiodarone patients (53%, 95% CI = 40 to 65%) and 13/31 procainamide patients (42%, 95% CI = 25 to 61%) required electrical therapy for VT termination. Hypotension led to cessation of medicine infusion or immediate direct current cardioversion (DCCV) in 4/66 (6%, 95% CI = 2 to 15%) and 6/31 (19%, 95% CI = 7 to 37%) patients who received amiodarone and procainamide, respectively. Conclusions: Procainamide was not more effective than amiodarone for the termination of sustained VT, but the ability to detect a significant difference was limited by the study design and potential confounding. As used in practice, both agents were relatively ineffective and associated with clinically important proportions of patients with decreased blood pressure. ACADEMIC EMERGENCY MEDICINE 2010; 17:297-306 (C) 2010 by the Society for Academic Emergency Medicine. C1 [Marill, Keith A.; Senecal, Emily L.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Ruskin, Jeremy N.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [deSouza, Ian S.; Nishijima, Daniel K.] Suny Downstate Med Ctr, Dept Emergency Med, Brooklyn, NY 11203 USA. [Setnik, Gary S.] Mt Auburn Hosp, Dept Emergency Med, Cambridge, MA USA. [Stair, Thomas O.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Marill, KA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM kmarill@partners.org FU Eleanor and Miles Shore Scholars in Medicine Fellowship, Harvard Medical School, Boston, MA FX This work was presented at the Society for Academic Emergency Medicine annual meeting, Chicago, IL, May 2007.; This work was supported by the Eleanor and Miles Shore Scholars in Medicine Fellowship, Harvard Medical School, Boston, MA. NR 22 TC 12 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 2010 VL 17 IS 3 BP 297 EP 306 DI 10.1111/j.1553-2712.2010.00680.x PG 10 WC Emergency Medicine SC Emergency Medicine GA 562YR UT WOS:000275092500010 PM 20370763 ER PT J AU Ginde, AA Camargo, CA AF Ginde, Adit A. Camargo, Carlos A., Jr. TI Trends in Midlevel Provider Utilization SO ACADEMIC EMERGENCY MEDICINE LA English DT Letter C1 [Ginde, Adit A.] Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Ginde, AA (reprint author), Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO USA. EM adit.ginde@ucdenver.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 2010 VL 17 IS 3 BP 344 EP 344 DI 10.1111/j.1553-2712.2010.00686.x PG 1 WC Emergency Medicine SC Emergency Medicine GA 562YR UT WOS:000275092500019 PM 20148763 ER PT J AU Li, STT Tancredi, DJ Co, JPT West, DC AF Li, Su-Ting T. Tancredi, Daniel J. Co, John Patrick T. West, Daniel C. TI Factors Associated with Successful Self-Directed Learning Using Individualized Learning Plans During Pediatric Residency SO ACADEMIC PEDIATRICS LA English DT Article DE individualized learning plan; medical education; self-directed learning; survey ID MEDICAL PROFESSIONALISM; HEALTH-PROFESSIONS; LIFELONG; MILLENNIUM; EDUCATION; ACCURACY; VALIDITY; CHARTER AB Objective.-The aim of this study was to determine whether resident or program characteristics are associated with effective self-directed learning of residents. Methods.-A cross-sectional survey of pediatric and medicine/pediatric residents and program directors from a nationally representative sample of residency programs was conducted. Self-directed learning efficacy was measured by resident-reported progress on learning goals from their most recent individualized learning plan (ILP). Multilevel linear regression models were used to analyze the relationship between learner and program characteristics and self-directed learning efficacy of residents. Results.-All program directors of participating programs (N = 46) completed the survey; the response rate from residents was 57% (992/1739). At the time of the survey, 78% of residents had previously written an ILP. Most residents achieved moderate self-directed learning efficacy. The most important factors associated with greater self-directed learning efficacy included using a system to track one's own progress in achieving learning goals, higher score on a propensity toward lifelong learning scale, and reporting greater confidence in self-directed learning abilities. Program characteristics, including program-level support for ILPs, had little or mixed association with resident self-directed learning efficacy. Conclusions.-The most important factors associated with effective self-directed learning were resident characteristics. Our findings imply that residency programs should invest their limited resources in curricula that help residents develop measurable goals and systems for tracking progress toward goal attainment. Since propensity toward lifelong learning was an important factor, medical schools and residency training programs should enhance their efforts to develop this characteristic in learners. C1 [Li, Su-Ting T.; Tancredi, Daniel J.] Univ Calif Davis, Dept Pediat, Sacramento, CA 95817 USA. [Co, John Patrick T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Massachusetts Gen Hosp,Off Grad Med Educ, Boston, MA 02115 USA. [West, Daniel C.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Li, STT (reprint author), Univ Calif Davis, Dept Pediat, 2516 Stockton Blvd, Sacramento, CA 95817 USA. EM su-ting.li@ucdmc.ucdavis.edu RI Tancredi, Daniel/O-3381-2013 OI Tancredi, Daniel/0000-0002-3884-7907 FU Association of Pediatric; Bronx-Lebanon; Upstate New York; University of California Los Angeles; Lutheran General; University of Connecticut; New York Presbyterian Hospital Cornell; St Vincent; Texas Tech; Carolinas Medical; Blank Children's; Louisiana State University New Orleans; Driscoll Children's; University of Missouri; St Baniabas; University of Nebraska Medical Center/Creighton; University of Kansas; New York Methodist Hospital; Coopers; University of Vermont; University of Utah; University of New Mexico; Medical College of Georgia; Naval Medical Center; Marshfield Clinic; Orlando Health; Goryeb; Marshall University; Medical College of Wisconsin; St Joseph's Hospital and Medical Center, Phoenix; University of California, Davis; Tripler Army; West Virginia University Morgantown; East Tennessee State University; Elmhurst; University of Colorado; St Louis University; Medical University of South Carolina; University of Washington; Harbor-University of California Los Angeles; Jersey Shore University; A.I. du Pont/Jefferson; University of South Alabama; University of California, San Francisco; Morehouse School of Medicine; Kaiser Los Angeles; Maine Medical Center FX Funding for this study was provided in part by a Special (Principal Investigator was Dr Su-Ting Li) Projects grant from the Association of Pediatric Program Directors. We thank the following program directors and residency training programs for participating in our study: Ayoade Adeniyi, MD (Bronx-Lebanon); John Andrake, MD (Upstate New York); Virginia Barrow, MD (University of California Los Angeles); Frank Belmonte, DO (Lutheran General); Priti Bhansali, MD (University of Connecticut); Susan Bostwick, MD (New York Presbyterian Hospital Cornell); Niceta C. Bradburn, MD (St Vincent); Tammy Camp, MD (Texas Tech); Suzette Caudle, MD (Carolinas Medical); Ken Cheyne, MD (Blank Children's); Bonnie Desselle, MD (Louisiana State University New Orleans); William Dirksen, MD (Driscoll Children's); Joy Drass, MD (University of Missouri); David Fagan, MD (St Baniabas); Cristina Fernandez, MD (University of Nebraska Medical Center/Creighton); Lisa Gilmer, MD (University of Kansas); Susan Gottlieb, MD (New York Methodist Hospital); Bill Graessle, MD (Coopers); Ann Guillot, MD (University of Vermont); Wendy Hobson, MD (University of Utah); Ben Hoffman, MD (University of New Mexico); Valera Hudson, MD (Medical College of Georgia); Christine Johnson, MD (Naval Medical Center); Divya Joshi, MD (Marshfield Clinic); Joan Meek, MD (Orlando Health); Alan Meltzer, MD (Goryeb); Bob Miller, MD (Marshall University); Jay Nocton, MD (Medical College of Wisconsin); Lilia Parra-Roide, MD (St Joseph's Hospital and Medical Center, Phoenix); Richard Pan, MD, MPH (University of California, Davis); Robert Pedersen, MD (Tripler Army); John Phillips, MD (West Virginia University Morgantown); Rebecca Powers, MD (East Tennessee State University); Gwen Raphan, MD (Elmhurst); Adam Rosenberg, MD (University of Colorado); Heidi Sallee, MD (St Louis University); Cassandra Salgado, MD (Medical University of South Carolina); Richard Shugerman, MD (University of Washington); Monica Sifuentes, MD (Harbor-University of California Los Angeles); Paul Schwartzberg, MD (Jersey Shore University); Glenn Stryjewski, MD (A.I. du Pont/Jefferson); Franklin Trimm, MD (University of South Alabama); Daniel West, MD (University of California, San Francisco); Yolanda Wimberly, MD (Morehouse School of Medicine); Steven Woods, MD (Kaiser Los Angeles); and Brian Youth, MD (Maine Medical Center). We also thank Mohammadreza Hojat, PhD, for permission to use the Jefferson Physician Lifelong Learning Scale in our study, and HayGroup for permission to use the Kolb Learning Style Inventory in our study. NR 29 TC 23 Z9 23 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAR-APR PY 2010 VL 10 IS 2 BP 124 EP 130 PG 7 WC Pediatrics SC Pediatrics GA 616DI UT WOS:000279188300008 PM 20206911 ER PT J AU Goisman, RM Levin, RM Krupat, E Pelletier, SR Alpert, JE AF Goisman, Robert M. Levin, Robert M. Krupat, Edward Pelletier, Stephen R. Alpert, Jonathan E. TI Psychiatric OSCE Performance of Students With and Without a Previous Core Psychiatry Clerkship SO ACADEMIC PSYCHIATRY LA English DT Article ID STRUCTURED CLINICAL EXAMINATION AB Objective: The OSCE has been demonstrated to be a reliable and valid method by which to assess students' clinical skills. An OSCE station was used to determine whether or not students who had completed a core psychiatry clerkship demonstrated skills that were superior to those who had not taken the clerkship and which areas discriminated between clerkship completers and noncompleters. Methods: One hundred thirty-six students took a 48-item, fourth-year OSCE with one psychiatry station. Sixty-three (46%) had already completed psychiatry, and 70 (51%) had not, with three unknown. Students were to take histories, perform mental status examinations, assess dangerousness, and propose the differential diagnosis and treatment plans. Results: Nine items differed significantly between completers and noncompleters, six concerning phenomenology and mental status and three concerning differential diagnosis. There were no differences regarding history, communication skills, or recommended interventions. Conclusion: Students may learn history taking, communication, and treatment planning in many settings. However, for the mental status examination, phenomenology, and differential diagnosis, completing a psychiatry clerkship was associated with better OSCE performance. C1 [Goisman, Robert M.] Massachusetts Mental Hlth Ctr, Boston, MA 02130 USA. [Goisman, Robert M.; Krupat, Edward] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA USA. [Goisman, Robert M.; Levin, Robert M.; Krupat, Edward; Pelletier, Stephen R.; Alpert, Jonathan E.] Harvard Univ, Sch Med, Boston, MA USA. [Levin, Robert M.] Mt Auburn Hosp, Dept Psychiat, Cambridge, MA USA. [Levin, Robert M.] Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA USA. [Alpert, Jonathan E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Goisman, RM (reprint author), Massachusetts Mental Hlth Ctr, 180 Morton St, Boston, MA 02130 USA. EM robert_goisman@hms.harvard.edu OI Alpert, Jonathan/0000-0002-4332-908X NR 11 TC 4 Z9 4 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAR-APR PY 2010 VL 34 IS 2 BP 141 EP 144 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 567GX UT WOS:000275434500015 PM 20224028 ER PT J AU Ozsunar, Y Mullins, ME Kwong, K Hochberg, FH Ament, C Schaefer, PW Gonzalez, RG Lev, MH AF Ozsunar, Yelda Mullins, Mark E. Kwong, Kenneth Hochberg, Fred H. Ament, Christine Schaefer, Pamela W. Gonzalez, R. Gilberto Lev, Michael H. TI Glioma Recurrence Versus Radiation Necrosis? A Pilot Comparison of Arterial Spin-Labeled, Dynamic Susceptibility Contrast Enhanced MRI, and FDG-PET Imaging SO ACADEMIC RADIOLOGY LA English DT Article DE Arterial spin labeling; perfusion MRI; brain tumors; glioma; perfusion; radiation necrosis ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN BRAIN-TUMORS; BLOOD-VOLUME MAPS; HISTOLOGIC GRADE; MICROVASCULAR PERMEABILITY; PROTON/PHOTON IRRADIATION; GLIOBLASTOMA-MULTIFORME; MALIGNANT GLIOMAS; PERFUSION MRI; FLOW AB Rationale and objectives: Distinguishing recurrent glial tumor from radiation necrosis can be challenging. The purpose of this pilot study was to preliminarily compare unenhanced arterial spin-labeled (ASL) imaging, dynamic susceptibility contrast-enhanced cerebral blood volume (DSCE-CBV) magnetic resonance imaging, and positron emission tomographic (PET) imaging in distinguishing predominant glioma recurrence or progression from predominant radiation necrosis in postoperative patients treated with proton-beam therapy. Methods: Patients with grade 11 to IV glioma previously treated with surgery and proton-beam therapy were enrolled on the basis of new enhancing nodules or masses with primary differential diagnoses of predominant tumor recurrence or progression versus radiation necrosis. ASL, DSCE-CBV, and PET examinations were assessed by visual qualitative and quantitative analysis for the detection of predominant tumor recurrence. Imaging results were correlated with a clinical-pathologic reference standard. Results: Thirty patients were studied, resulting in 33 ASL, 32 DSCE-CBV, and 26 PET examinations. On the basis of visual inspection, the sensitivities of PET, ASL, and DSCE-CBV examinations for detecting high-grade tumor foci were 81%, 88%, and 86%, respectively. The highest sensitivity values for quantitative ASL imaging were obtained using a normalized cutoff ratio of 1.3, resulting in sensitivity of 94% for ASL imaging and 71% for DSCE-CBV imaging. When predominant high-grade tumors with superimposed regions of predominant mixed radiation necrosis were excluded, DSCE-CBV sensitivity improved to 90%, but ASL sensitivity remained unchanged. Conclusions: Compared with DSCE-CBV imaging, ASL imaging may more accurately distinguish predominant recurrent high-grade glioma from radiation necrosis, especially in regions with mixed radiation necrosis, for which DSCE-CBV imaging may underestimate true blood volume because of leakage artifacts. C1 [Ozsunar, Yelda] Adrian Menderes Univ, Sch Med, Dept Radiol, Aydin, Turkey. [Mullins, Mark E.] Emory Univ, Dept Radiol, Atlanta, GA 30322 USA. [Kwong, Kenneth; Schaefer, Pamela W.; Gonzalez, R. Gilberto; Lev, Michael H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kwong, Kenneth; Schaefer, Pamela W.; Gonzalez, R. Gilberto; Lev, Michael H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hochberg, Fred H.] Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. [Kwong, Kenneth; Hochberg, Fred H.; Schaefer, Pamela W.; Gonzalez, R. Gilberto; Lev, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. [Ament, Christine] Boston Univ Eye Associates, Trygve Gunderson Eye Ctr, Boston, MA 02215 USA. RP Ozsunar, Y (reprint author), Adrian Menderes Univ, Sch Med, Dept Radiol, Hastane Caddesi, Aydin, Turkey. EM yeldaozsunar@gmail.com NR 50 TC 43 Z9 50 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2010 VL 17 IS 3 BP 282 EP 290 DI 10.1016/j.acra.2009.10.024 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 564RX UT WOS:000275235500004 PM 20060750 ER PT J AU Coleman, JJ Okoli, I Tegos, GP Holson, EB Wagner, FF Hamblin, MR Mylonakis, E AF Coleman, Jeffrey J. Okoli, Ikechukwu Tegos, George P. Holson, Edward B. Wagner, Florence F. Hamblin, Michael R. Mylonakis, Eleftherios TI Characterization of Plant-Derived Saponin Natural Products against Candida albicans SO ACS CHEMICAL BIOLOGY LA English DT Article ID VULVO-VAGINAL CANDIDIASIS; TRITERPENOID SAPONINS; PHOTODYNAMIC THERAPY; EPIDEMIOLOGIC SURVEY; ANTIFUNGAL COMPOUNDS; IN-VITRO; INFECTIONS; RESISTANCE; BIOFILMS; IDENTIFICATION AB Candida albicans is an opportunistic fungal pathogen capable of life threatening disseminated infections particularly in immunocompromised patients. Resistance to many clinically used antifungal agents has created a need to identify and develop a new generation of compounds for therapeutic use. A compound screen to identify potential antifungal natural products was undertaken, identifying 12 saponins, some of which have not been previously described. In the Caenorhabditis elegans model, some saponins conferred nematode survival comparable to that of amphotericin B. Of the 12 antifungal saponins identified, two were selected for further analysis. C albicans isolates were inhibited by these compounds at relatively low concentrations (16 and 32 mu g mL(-1)) including isolates resistant to clinically used antifungal agents. C albicans hyphae and biofilm formation were also disrupted in the presence of these natural products, and studies demonstrate that fungal cells in the presence of saponins are more susceptible to salt-induced osmotic stress. Although saponins are known for their hemolytic activity, no hemolysis of erythrocytes was observed at three times the minimal inhibitory concentration for C. albicans, suggesting the saponins may have a preference for binding to fungal ergosterol when compared to cholesterol. Importantly, when used in combination with photosensitizer compounds, the fungus displayed increased susceptibility to photodynamic inactivation due to the ability of the saponins to increase cell permeability, thereby facilitating penetration of the photosensitizers. The large proportion of compounds identified as antifungal agents containing saponin structural features suggests it may be a suitable chemical scaffold for a new generation of antifungal compounds. C1 [Coleman, Jeffrey J.; Okoli, Ikechukwu; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Holson, Edward B.; Wagner, Florence F.] Massachusetts Inst Technol & Harvard, Broad Inst, Cambridge, MA USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM emylonakis@partners.org RI Tegos, George/C-8830-2011; Coleman, Jeffrey/E-2981-2015; OI Hamblin, Michael/0000-0001-6431-4605; Coleman, Jeffrey/0000-0001-8579-1996 FU NIH [Al075286, Al050875]; Broad Institute of MIT and Harvard; National Cancer Institute's Initiative for Chemical Genetics [N01-CO-12400] FX The authors thank B. Burgwyn Fuchs for her assistance with microscopy Support was provided by NIH R01 awards Al075286 (E M), and Al050875 (G P T and M R H) and by the Broad Institute of MIT and Harvard This project has also been funded in part by the National Cancer Institute's Initiative for Chemical Genetics under contract N01-CO-12400 and has been performed with the assistance of the Chemical Biology Platform of the Broad Institute NR 44 TC 58 Z9 60 U1 3 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD MAR PY 2010 VL 5 IS 3 BP 321 EP 332 DI 10.1021/cb900243b PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 569VA UT WOS:000275629200008 PM 20099897 ER PT J AU Semenas, E Nozari, A Sharma, HS Basu, S Rubertsson, S Wiklund, L AF Semenas, E. Nozari, A. Sharma, H. S. Basu, S. Rubertsson, S. Wiklund, L. TI Sex differences in cerebral injury after severe haemorrhage and ventricular fibrillation in pigs SO ACTA ANAESTHESIOLOGICA SCANDINAVICA LA English DT Article ID CATALYZED LIPID-PEROXIDATION; TRAUMATIC CARDIAC-ARREST; PERINATAL BRAIN-INJURY; NITRIC-OXIDE; BLOOD-FLOW; CARDIOPULMONARY-RESUSCITATION; GENDER-DIFFERENCES; HYPERTONIC SALINE; OXIDATIVE INJURY; METHYLENE-BLUE AB Background Experimental studies of haemorrhagic shock have documented a superior haemodynamic response and a better outcome in female animals as compared with male controls. Such sexual dimorphism has, nevertheless, not been reported after circulatory arrest that follows exsanguination and shock. We aimed to study differences in cerebral injury markers after exsanguination cardiac arrest in pre-pubertal piglets. The hypothesis was that cerebral injury is less extensive in female animals, and that this difference is independent of sexual hormones or choice of resuscitative fluid. Methods Thirty-two sexually immature piglets (14 males and 18 females) were subjected to 5 min of haemorrhagic shock followed by 2 min of ventricular fibrillation and 8 min of cardiopulmonary resuscitation, using three resuscitation fluid regimens (whole blood, hypertonic saline and dextran, or acetated Ringers' solution plus whole blood and methylene blue). Haemodynamic values, cellular markers of brain injury and brain histology were studied. Results After successful resuscitation, female piglets had significantly greater cerebral cortical blood flow, tended to have lower S-100 beta values and a lower cerebral oxygen extraction ratio. Besides, in female animals, systemic and cerebral venous acidosis were mitigated. Female piglets exhibited a significantly smaller increase in neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in their cerebral cortex, smaller blood-brain-barrier (BBB) disruption and significantly smaller neuronal injury. Conclusion After resuscitation from haemorrhagic circulatory arrest, cerebral reperfusion is greater, and BBB permeability and neuronal injury is smaller in female piglets. An increased cerebral cortical iNOS and nNOS expression in males implies a mechanistic relationship with post-resuscitation neuronal injury and warrants further investigation. C1 [Semenas, E.; Sharma, H. S.; Rubertsson, S.; Wiklund, L.] Univ Uppsala Hosp, Dept Surg Sci Anesthesiol & Intens Care, Fac Med, S-75185 Uppsala, Sweden. [Nozari, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Basu, S.] Univ Uppsala Hosp, Dept Publ Hlth & Caring Sci Clin Nutr & Metab, Fac Med, S-75185 Uppsala, Sweden. RP Semenas, E (reprint author), Univ Uppsala Hosp, Dept Surg Sci Anesthesiol & Intens Care, Fac Med, S-75185 Uppsala, Sweden. EM egidijus.semenas@gmail.com RI Sharma, Aruna/D-4430-2011; Sharma, Hari/G-4508-2016 FU Laerdal Foundation for Acute Medicine, Stavanger, Norway FX The research was supported, in part, by the Laerdal Foundation for Acute Medicine, Stavanger, Norway. NR 41 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-5172 J9 ACTA ANAESTH SCAND JI Acta Anaesthesiol. Scand. PD MAR PY 2010 VL 54 IS 3 BP 343 EP 353 DI 10.1111/j.1399-6576.2009.02125.x PG 11 WC Anesthesiology SC Anesthesiology GA 552SF UT WOS:000274313000012 PM 19764903 ER PT J AU Pakhomova, ON Taylor, AB Becker, A Holloway, SP Kannan, TR Baseman, JB Hart, PJ AF Pakhomova, Olga N. Taylor, Alexander B. Becker, Argentina Holloway, Stephen P. Kannan, T. R. Baseman, Joel B. Hart, P. John TI Crystallization of community-acquired respiratory distress syndrome toxin from Mycoplasma pneumoniae SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID CHRONIC ASTHMA; IDENTIFICATION; PERTUSSIS; PROTEIN AB Community-acquired respiratory distress syndrome toxin (CARDS TX) is a 591-amino-acid protein with ADP-ribosyltransferase and vacuolating activities that damages the cells lining the respiratory tracts of patients infected with the bacterial pathogen Mycoplasma pneumoniae. Crystals of CARDS TX were grown in space group C2, with unit-cell parameters a = 191.4, b = 107.4, c = 222.1 angstrom, beta = 90.6 degrees. A complete 2.2 angstrom data set was obtained from a single CARDS TX crystal. C1 [Pakhomova, Olga N.; Taylor, Alexander B.; Becker, Argentina; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Pakhomova, Olga N.; Taylor, Alexander B.; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. [Kannan, T. R.; Baseman, Joel B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Hart, P. John] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Dept Vet Affairs, San Antonio, TX 78229 USA. RP Hart, PJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. EM pjhart@biochem.uthscsa.edu FU Robert A. Welch Foundation [AQ-1399]; IH [U19 AI070412]; Kleberg Foundation FX This work was supported by the Robert A. Welch Foundation Grant AQ-1399 (to PJH), by IH grant U19 AI070412 (to JBB) and by the Kleberg Foundation (to JBB). NR 20 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD MAR PY 2010 VL 66 BP 294 EP 296 DI 10.1107/S1744309110000114 PN 3 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 562ND UT WOS:000275057700019 PM 20208164 ER PT J AU Papadaki, T Iaccheri, B Fiore, T Zacharopoulos, I Thadani, S Christen, W Androudi, S Foster, CS AF Papadaki, Thekla Iaccheri, Barbara Fiore, Tito Zacharopoulos, Ioannis Thadani, Sunil Christen, William Androudi, Sofia Foster, C. Stephen TI Serum soluble interleukin-2 receptor levels do not correlate with an associated systemic disease in patients with uveitis SO ACTA OPHTHALMOLOGICA LA English DT Letter ID CYTOKINES C1 [Foster, C. Stephen] Ocular Immunol & Uveitis Fdn, Massachusetts Eye Res & Surg Inst, Cambridge, MA 02142 USA. [Papadaki, Thekla; Iaccheri, Barbara; Fiore, Tito; Zacharopoulos, Ioannis; Thadani, Sunil; Androudi, Sofia; Foster, C. Stephen] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Christen, William] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Foster, CS (reprint author), Ocular Immunol & Uveitis Fdn, Massachusetts Eye Res & Surg Inst, 5 Cambridge Ctr,8th Floor, Cambridge, MA 02142 USA. EM fosters@uveitis.org NR 5 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-375X J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD MAR PY 2010 VL 88 IS 2 BP e28 EP e29 DI 10.1111/j.1755-3768.2008.01422.x PG 2 WC Ophthalmology SC Ophthalmology GA 560WB UT WOS:000274933700016 PM 19493254 ER PT J AU Barnhill, RL Cerroni, L Cook, M Elder, DE Kerl, H LeBoit, PE McCarthy, SW Mihm, MC Mooi, WJ Piepkorn, MW Prieto, VG Scolyer, RA AF Barnhill, Raymond L. Cerroni, Lorenzo Cook, Martin Elder, David E. Kerl, Helmut LeBoit, Philip E. McCarthy, Stanley W. Mihm, Martin C. Mooi, Wolter J. Piepkorn, Michael W. Prieto, Victor G. Scolyer, Richard A. TI State of the Art, Nomenclature, and Points of Consensus and Controversy Concerning Benign Melanocytic Lesions: Outcome of an International Workshop SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE melanocytic nevus; spitz nevus; melanoma; blue nevus; congenital nevus; nevocellular nevi; nevi; spindle cell nevus; dysplastic nevus; atypical nevus; benign melanocytic tumors; benign melanocytic neoplasms; workshop; consensus conference ID SPINDLE CELL NEVUS; DEEP PENETRATING NEVUS; PIGMENTED-EPITHELIOID-MELANOCYTOMA; GERMAN-DERMATOLOGICAL-SOCIETY; MALIGNANT-MELANOMA REGISTRY; MULTICENTER CASE-CONTROL; COMPONENTS CLONAL NEVUS; DYSPLASTIC NEVI; BLUE NEVUS; SPITZ NEVI AB The following communication summarizes the proceedings of a one-day International Workshop focusing on the histology of benign melanocytic nevi. Areas of controversy identified in 6 focus sessions were the nomenclature and relationships among common nevi including nevi with halo reactions, traumatized nevi, "dysplastic'' nevi, and nevi from particular anatomic sites; developmental biology and frequency of malignant transformation associated with congenital nevi; the characterization and biologic nature of atypical spitzoid neoplasms; the basic definition of particular melanocytic cellular phenotypes, and the nomenclature and biologic nature of many candidate blue nevi, combined nevi, and other controversial lesions such as deep penetrating nevus and pigmented epithelioid melanocytoma. Concentrated data collection and follow-up, molecular characterization, and future consensus Workshops may facilitate the resolution of some of these problems. The Group recommended the description of ambiguous or 'borderline'' lesions as tumors with indeterminate or uncertain biologic/malignant potential. The participants also advised that such lesions at a minimum should be managed by complete excision with clear surgical margins. C1 [Barnhill, Raymond L.] Hop St Louis, Dept Dermatol, Paris, France. [Barnhill, Raymond L.] Hop St Louis, Dept Pathol, Paris, France. [Cerroni, Lorenzo; Kerl, Helmut] Med Univ Graz, Dept Dermatol, Graz, Austria. [Cook, Martin] Royal Surrey Cty Hosp, Dept Pathol, Guildford, Surrey, England. [Elder, David E.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [LeBoit, Philip E.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [LeBoit, Philip E.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [McCarthy, Stanley W.; Scolyer, Richard A.] Royal Prince Alfred Hosp, Melanoma Inst Australia, Sydney, NSW, Australia. [McCarthy, Stanley W.; Scolyer, Richard A.] Univ Sydney, Sydney, NSW 2006, Australia. [Mihm, Martin C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mooi, Wolter J.] Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Pathol, Amsterdam, Netherlands. [Piepkorn, Michael W.] Univ Washington, Div Dermatol, Seattle, WA 98195 USA. [Prieto, Victor G.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. RP Barnhill, RL (reprint author), Hop St Louis, Dept Dermatol, Paris, France. EM raymond.barnhill@sls.aphp.fr OI Scolyer, Richard/0000-0002-8991-0013 NR 104 TC 34 Z9 34 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD MAR PY 2010 VL 17 IS 2 BP 73 EP 90 DI 10.1097/PAP.0b013e3181cfe758 PG 18 WC Pathology SC Pathology GA 564XB UT WOS:000275250600001 PM 20179431 ER PT J AU Chew, I Oliva, E AF Chew, Ivy Oliva, Esther TI Endometrial Stromal Sarcomas A Review of Potential Prognostic Factors SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE endometrial stromal nodule; endometrial stromal sarcoma; undifferentiated endometrial sarcoma; prognostic factors ID SMOOTH-MUSCLE TUMORS; FLOW CYTOMETRIC ANALYSIS; NUCLEAR BETA-CATENIN; HIGH-GRADE SARCOMA; SEX-CORD TUMORS; UTERINE SARCOMAS; MESENCHYMAL TUMORS; CLINICOPATHOLOGIC ANALYSIS; GLANDULAR DIFFERENTIATION; PROGESTERONE-RECEPTORS AB Endometrial stromal tumors are uncommon mesenchymal tumors of the uterus. The classification of these tumors has evolved and the most current World Health Organization classification (2003) divides these neoplasms into: endometrial stromal nodule, low-grade endometrial stromal sarcoma, and undifferentiated endometrial sarcoma. The salient clinicopathologic features of these tumors are described, and a comprehensive review of literature pertaining to potential prognostic factors in endometrial stromal sarcomas is provided. Clinical factors, including age, race, parity and menopausal status, and pathologic factors, including tumor size, tumor stage, nuclear atypia, mitotic activity, tumor necrosis, lymphovascular space invasion, DNA ploidy and proliferative activity, and expression of hormone receptors, have been explored with varying outcomes. Surgicopathologic stage seems to be the most important prognostic factor in low-grade endometrial stromal sarcomas. The impact of other prognostic factors on survival is unclear or controversial, especially in patients with stage I tumors. C1 [Chew, Ivy; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 251A, Boston, MA 02114 USA. EM eoliva@partners.org NR 103 TC 25 Z9 29 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD MAR PY 2010 VL 17 IS 2 BP 113 EP 121 DI 10.1097/PAP.0b013e3181cfb7c2 PG 9 WC Pathology SC Pathology GA 564XB UT WOS:000275250600003 PM 20179433 ER PT J AU Blagosklonny, MV Campisi, J Sinclair, DA Bartke, A Blasco, MA Bonner, WM Bohr, VA Brosh, RM Brunet, A DePinho, RA Donehower, LA Finch, CE Finkel, T Gorospe, M Gudkov, AV Hall, MN Hekimi, S Helfand, SL Karlseder, J Kenyon, C Kroemer, G Longo, V Nussenzweig, A Osiewacz, HD Peeper, DS Rando, TA Rudolph, KL Sassone-Corsi, P Serrano, M Sharpless, NE Skulachev, VP Tilly, JL Tower, J Verdin, E Vijg, J AF Blagosklonny, Mikhail V. Campisi, Judy Sinclair, David A. Bartke, Andrzej Blasco, Maria A. Bonner, William M. Bohr, Vilhelm A. Brosh, Robert M., Jr. Brunet, Anne DePinho, Ronald A. Donehower, Lawrence A. Finch, Caleb E. Finkel, Toren Gorospe, Myriam Gudkov, Andrei V. Hall, Michael N. Hekimi, Siegfried Helfand, Stephen L. Karlseder, Jan Kenyon, Cynthia Kroemer, Guido Longo, Valter Nussenzweig, Andre Osiewacz, Heinz D. Peeper, Daniel S. Rando, Thomas A. Rudolph, K. Lenhard Sassone-Corsi, Paolo Serrano, Manuel Sharpless, Norman E. Skulachev, Vladimir P. Tilly, Jonathan L. Tower, John Verdin, Eric Vijg, Jan TI Impact papers on aging in 2009 SO AGING-US LA English DT Review DE aging; senescence; signal transduction; genes for longevity ID LIFE-SPAN EXTENSION; SINGLE-NUCLEOTIDE POLYMORPHISMS; TELOMERE-DYSFUNCTIONAL MICE; STEM-CELL HOMEOSTASIS; DNA-DAMAGE RESPONSE; DROSOPHILA-MELANOGASTER; DIETARY RESTRICTION; PROTEIN-KINASE; GENETICALLY INTERACTS; CALORIE RESTRICTION AB The editorial board of Aging reviews research papers published in 2009, which they believe have or will have a significant impact on aging research. Among many others, the topics include genes that accelerate aging or in contrast promote longevity in model organisms, DNA damage responses and telomeres, molecular mechanisms of life span extension by calorie restriction and pharmacologic interventions into aging. The emerging message in 2009 is that aging is not random but determined by a genetically-regulated longevity network and can be decelerated both genetically and pharmacologically. C1 [Blagosklonny, Mikhail V.] Roswell Pk Canc Inst, Dept Cell Stress Biol, BLSC, Buffalo, NY 14263 USA. [Campisi, Judy] Buck Inst Age Res, Novato, CA USA. [Sinclair, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Bartke, Andrzej] So Illinois Univ, Springfield, IL USA. [Blasco, Maria A.; Serrano, Manuel] Spanish Natl Canc Ctr, Madrid, Spain. [Bonner, William M.; Nussenzweig, Andre] NCI, NIH, Bethesda, MD 20892 USA. [Bohr, Vilhelm A.; Brosh, Robert M., Jr.; Gorospe, Myriam] NIA, NIH, Baltimore, MD 21224 USA. [Brunet, Anne; Rando, Thomas A.] Stanford Univ, Stanford, CA 94305 USA. [DePinho, Ronald A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Donehower, Lawrence A.] Baylor Coll Med, Houston, TX 77030 USA. [Finch, Caleb E.; Longo, Valter; Tower, John] Univ So Calif, Los Angeles, CA USA. [Finkel, Toren] NHLBI, NIH, Bethesda, MD 20892 USA. [Hall, Michael N.] Univ Basel, Basel, Switzerland. [Hekimi, Siegfried] McGill Univ, Montreal, PQ, Canada. [Helfand, Stephen L.] Brown Univ, Providence, RI 02912 USA. [Karlseder, Jan] Salk Inst Biol Studies, La Jolla, CA USA. [Kenyon, Cynthia; Verdin, Eric] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kroemer, Guido] INSERM, U848, Villejuif, France. [Osiewacz, Heinz D.] Goethe Univ Frankfurt, Frankfurt, Germany. [Peeper, Daniel S.] Netherlands Canc Inst, Amsterdam, Netherlands. [Rudolph, K. Lenhard] Hannover Med Sch, D-3000 Hannover, Germany. [Sassone-Corsi, Paolo] Univ Calif Irvine, Irvine, CA USA. [Sharpless, Norman E.] Univ N Carolina, Chapel Hill, NC USA. [Skulachev, Vladimir P.] Moscow MV Lomonosov State Univ, Moscow, Russia. [Tilly, Jonathan L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vijg, Jan] Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Blagosklonny, MV (reprint author), Roswell Pk Canc Inst, Dept Cell Stress Biol, BLSC, L3-312,Elm & Carlton St, Buffalo, NY 14263 USA. EM Blagosklonny@oncotarget.com RI Osiewacz, Heinz/D-3454-2011; Sassone-Corsi, Paolo/H-6182-2011; Skulachev, Vladimir/J-4164-2012; Kroemer, Guido/B-4263-2013; Serrano, Manuel/H-2634-2015; Blasco , Maria A./M-1694-2014; Bartke, Andzej/D-6640-2017; OI Skulachev, Vladimir/0000-0003-4886-2243; Serrano, Manuel/0000-0001-7177-9312; Blasco , Maria A./0000-0002-4211-233X; Bartke, Andzej/0000-0002-2569-557X; Verdin, Eric/0000-0003-3703-3183; Sinclair, David/0000-0002-9936-436X FU NCI NIH HHS [R01 CA084628]; NIA NIH HHS [R01 AG011833, R01 AG024353, R01 AG028730] NR 115 TC 19 Z9 20 U1 0 U2 7 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD MAR PY 2010 VL 2 IS 3 BP 111 EP 121 PG 11 WC Cell Biology SC Cell Biology GA 589AE UT WOS:000277115300001 PM 20351400 ER PT J AU Elrefaei, M Burke, CM Baker, CAR Jones, NG Bousheri, S Bangsberg, DR Cao, HY AF Elrefaei, Mohamed Burke, Candace M. Baker, Chris A. R. Jones, Norman G. Bousheri, Stephanie Bangsberg, David R. Cao, Huyen TI HIV-Specific TGF-beta-Positive CD4(+) T Cells Do Not Express Regulatory Surface Markers and Are Regulated by CTLA-4 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID GROWTH-FACTOR-BETA; ACTIVE ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; INFECTED INDIVIDUALS; CYTOKINE PRODUCTION; PERIPHERAL-BLOOD; IMMUNE-RESPONSES; UP-REGULATION; IN-VIVO; INTERLEUKIN-10 AB CD4(+) T cell dysfunction in HIV-1 infection is associated with increased CTLA-4 and TGF-beta expression. In this study we described a population of TGF-beta-positive CD4(+) T cells with multiple HIV specificities. These HIV-specific TGF-beta-positive CD4(+) T cells did not display the immunophenotypic patterns traditionally attributed to regulatory CD4(+) T cells. TGF-beta-positive CD4(+) T cells were FOXP3 negative, CD25 negative, and displayed a heterogeneous surface expression of CD127. We also examined one potential mechanism for regulating TGF-beta expression by HIV-specific CD4(+) T cells. Blocking of the TGF-beta receptor II led to increased HIV-specific IFN-gamma-positive CD4(+) and CD8(+) T cell responses. Interestingly, HIV-specific TGF-beta-positive CD4(+) T cells did not substantially express CTLA-4. Nevertheless, CTLA-4 blockade resulted in a significant decrease in HIV-specific TGF-beta-positive CD4(+) T cell responses, and a concomitant increase in HIV-specific IFN-gamma-positive CD4(+) T cell responses. Our study proposes a mechanism by which HIV-specific TGF-beta production may be regulated by CTLA-4 engagement. C1 [Elrefaei, Mohamed; Burke, Candace M.; Baker, Chris A. R.; Jones, Norman G.; Bousheri, Stephanie; Cao, Huyen] Calif Dept Publ Hlth, Richmond, CA 94804 USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Harvard Initiat Global Hlth, Cambridge, MA 02138 USA. RP Elrefaei, M (reprint author), Calif Dept Publ Hlth, 850 Marina Bay Pkwy VRDL, Richmond, CA 94804 USA. EM melrefae@unch.unc.edu FU NIH [AI43885, MM54907, AI71772]; California Research Center for the Biology of HIV in Minorities FX This work was supported by NIH Grants AI43885, MM54907, and AI71772, and California Research Center for the Biology of HIV in Minorities grant, UC Davis. NR 50 TC 7 Z9 9 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 MAR PY 2010 VL 26 IS 3 BP 329 EP 337 DI 10.1089/aid.2009.0149 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 574IT UT WOS:000275983300010 PM 20433405 ER PT J AU Long, AD AF Long, Aidan TI Aeroallergen sensitization in asthma: Genetics, environment, and pathophysiology SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article; Proceedings Paper CT Eastern Allergy Conference CY MAY 02, 2009 CL Palm Beach, FL DE Airway; allergen; anti-IgE; asthma; dendritic; epithelium; IgE; inflammation; remodeling ID ANTI-IGE ANTIBODY; HOUSE-DUST MITE; EPSILON-F-RI; DENDRITIC CELLS; ALLERGIC-ASTHMA; AIRWAY INFLAMMATION; IMMUNE-RESPONSES; OMALIZUMAB; INNATE; EXPRESSION AB A complex interplay of genetic predisposition and environmental influences results in the clinical picture of allergic asthma. This article addresses recently identified genetic markers and environmental factors that contribute to disease development in asthma. Focus is placed on aspects of the innate immune system, including inherent properties of allergens, the active role of airway epithelium, and the central importance of dendritic cells together with the pathophysiological processes in which these factors interact. Implications of these processes for asthma therapy, with a focus on anti-IgE treatment are also discussed. (Allergy Asthma Proc 31:89-95, 2010; doi: 10.2500/aap.2010.31.3328) C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, DRAI, Boston, MA 02114 USA. RP Long, AD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, DRAI, COX 201,55 Fruit St, Boston, MA 02114 USA. EM aalong@partners.org NR 42 TC 6 Z9 6 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAR-APR PY 2010 VL 31 IS 2 BP 89 EP 95 DI 10.2500/aap.2010.31.3328 PG 7 WC Allergy SC Allergy GA 589OU UT WOS:000277162300001 PM 20406590 ER PT J AU Barnes, DE Covinsky, KE Whitmer, RA Kuller, LH Lopez, OL Yaffe, K AF Barnes, Deborah E. Covinsky, Kenneth E. Whitmer, Rachel A. Kuller, Lewis H. Lopez, Oscar L. Yaffe, Kristine TI Commentary on "Developing a national strategy to prevent dementia: Leon Thal Symposium 2009." Dementia risk indices: A framework for identifying individuals with a high dementia risk SO ALZHEIMERS & DEMENTIA LA English DT Article ID CARDIOVASCULAR HEALTH COGNITION; OLDER-ADULTS; PROGNOSTIC INDEX; BREAST-CANCER; VALIDATION; PREDICTION; SCORE; MORTALITY C1 [Barnes, Deborah E.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA 94121 USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Whitmer, Rachel A.] Kaiser Div Res, Oakland, CA USA. [Kuller, Lewis H.; Lopez, Oscar L.] Univ Pittsburgh, Pittsburgh, PA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Psychiat, 4150 Clement St,151R, San Francisco, CA 94121 USA. EM deborah.bames@ucsf.edu FU National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295]; National Institute on Aging [AG15928]; National Institute of Neurological Disorders and Stroke; National Institutes of Health [K01 AG024069]; Alzheimer's Association [IIRG-06-27306]; NIH/NCRR UCSF-CTSI [UL1 RR024131] FX The Cardiovascular Health Study (CHS) was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number U01 HL080295 from the National Heart, Lung, and Blood Institute, and grant AG15928 from the National Institute on Aging with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. Dr Barnes is funded through a K01 Career Development Award (K01 AG024069) from the National Institutes of Health and an Alzheimer's Association award (IIRG-06-27306). This project also was supported by NIH/NCRR UCSF-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 21 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAR PY 2010 VL 6 IS 2 BP 138 EP 141 DI 10.1016/j.jalz.2010.01.005 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 582DR UT WOS:000276576400009 PM 20298975 ER PT J AU Setoguchi, S Higgins, JM Mogun, H Mootha, VK Avorn, J AF Setoguchi, Soko Higgins, John M. Mogun, Helen Mootha, Vamsi K. Avorn, Jerry TI Propranolol and the risk of hospitalized myopathy: Translating chemical genomics findings into population-level hypotheses SO AMERICAN HEART JOURNAL LA English DT Article ID VALIDITY AB Background A recent large-scale, chemical screening study raised the hypothesis that propranolol may increase the risk of myopathy. We tested this hypothesis in a large population to assess whether (1) propranolol use is associated with an increased risk of myopathy and (2) the concurrent use of propranolol with a statin may further increase risk of myopathy. Methods New users of propranolol and other beta-blockers (BBs) aged >= 65 were identified using data from Medicare and drug benefit programs in 2 states (1994-2005). The primary end point studied was hospitalization for myopathy or rhabdomyolysis. We used stratified Cox proportional hazards regression to estimate the multivariate-adjusted effect of propranolol compared to other BBs and controlled for demographic variables, risk factors for myopathy, other comorbidities, and health service use measures. We also assessed whether co-use of propranolol and statin further increases the risk, by including an interaction term for use of propranolol and statins. Results We identified 9,304 initiators of propranolol and 130,070 initiators of other BBs and found 30 cases of hospitalized myopathy in 15,477 person-years (PYs) of propranolol use and 523 in 343,132 PYs of other BB use. Comparing propranolol with other BB users, the adjusted hazard ratio was 1.45 (95% CI 1.00-2.11) for myopathy and 1.48 (95% CI 0.82-2.67) for rhabdomyolysis. We could not detect interaction between propranolol and statins due to limited power. Similar results were observed when propranolol users were compared to other antihypertensive drug users. Conclusions Propranolol may be associated with a 45% increased risk of hospitalized myopathy in the elderly. Our study illustrates how results from in vitro chemical screens can be translated into hypotheses about drug toxicity at the population level. (Am Heart J 2010; 159: 428-33.) C1 [Setoguchi, Soko; Mogun, Helen; Avorn, Jerry] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02130 USA. [Higgins, John M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Mootha, Vamsi K.] MIT & Harvard, Broad Inst, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA. [Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Setoguchi, S (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02130 USA. EM ssetoguchi@partners.org FU Divisional fund; American Diabetes Association/Smith Family Foundation FX Divisional fund; American Diabetes Association/Smith Family Foundation. NR 12 TC 3 Z9 3 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 MAR PY 2010 VL 159 IS 3 BP 428 EP 433 DI 10.1016/j.ahj.2009.12.008 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 571XH UT WOS:000275788900014 PM 20211305 ER PT J AU Acharjee, S Qin, JE Murphy, SA McCabe, C Cannon, CP AF Acharjee, Subroto Qin, Jie Murphy, Sabina A. McCabe, Carolyn Cannon, Christopher P. TI Distribution of Traditional and Novel Risk Factors and Their Relation to Subsequent Cardiovascular Events in Patients With Acute Coronary Syndromes (from the PROVE IT-TIMI 22 Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; HEART-DISEASE; CHOLESTEROL LEVELS; RANDOMIZED-TRIAL; FOLLOW-UP; MEN; PREDICTION; WOMEN; SIMVASTATIN; PREVENTION AB Current guidelines recommend risk stratification largely based on traditional risk factors such as those in the Framingham Risk Score. We studied the distribution of 12 traditional and non-traditional risk markers (age >= 65 years, male gender, family history of premature coronary heart disease, low-density lipoprotein cholesterol >= 70 mg/di, high-density lipoprotein cholesterol <40 mg/di in men and <50 mg/dl in women, systolic blood pressure > 130 mm Hg, diabetes mellitus, smoking, C-reactive protein >= 2 mg/L, triglycerides >150 mg/di, prediabetes defined as a fasting glucose level 100 to 125 mg/di or hemoglobin Ale >6, and obesity defined as body mass index >= 30 kg/m(2)) in 3,675 patients from the PROVE IT-TIMI 22 trial at 4 months and evaluated the risk of cardiovascular events stratified by the number of risk factors. The median number of risk factors was 5. In individual risk factor subgroups, men, smokers, hypertensives, and patients with increased low-density lipoprotein cholesterol had just that added risk factor compared to their counterparts (median 5 vs 4). In contrast, patients with diabetes, prediabetes, and increased triglycerides, C-reactive protein, or body mass index had not only that, but also another added risk factor (median 6 vs 4). A higher risk factor count was strongly related with increased rate of death, myocardial infarction, unstable angina, stroke, or revascularization, from 0% to 38.6% at 2 years for 0 to >= 9 risk factors (p < 0.0001). In conclusion, with the observed "clustering" of risk factors and the link between increasing risk factor count and adverse outcomes in a patient with 1 diagnosed risk factor, a comprehensive review of traditional and novel risk factors is important to fully assess cardiovascular risk. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:619-623) C1 [Qin, Jie; Murphy, Sabina A.; McCabe, Carolyn; Cannon, Christopher P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Acharjee, Subroto] SUNY Buffalo, Dept Med, Sch Med, Buffalo, NY 14260 USA. RP Cannon, CP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. EM cpcannon@partners.org FU Bristol-Myers Squibb, New York, New York; Sankiyo, Parsippany, New York FX The PROVE IT-TIMI 22 Study was supported by a research grant from Bristol-Myers Squibb, New York, New York; and Sankiyo, Parsippany, New York. NR 23 TC 10 Z9 10 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2010 VL 105 IS 5 BP 619 EP 623 DI 10.1016/j.amjcard.2009.10.042 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 602KD UT WOS:000278137100007 PM 20185006 ER PT J AU Krempf, M Parhofer, KG Steg, G Bhatt, DL Ohman, M Rother, J Goto, S Pasquet, B Wilson, PWF AF Krempf, Michel Parhofer, Klaus G. Steg, Gabriel Bhatt, Deepak L. Ohman, Magnus Roether, Joachim Goto, Shinya Pasquet, Blandine Wilson, Peter W. F. CA Reach Registry Investigators TI Cardiovascular Event Rates in Diabetic and Nondiabetic Individuals With and Without Established Atherothrombosis (from the REduction of Atherothrombosis for Continued Health [REACH] Registry) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; PRIOR MYOCARDIAL-INFARCTION; METABOLIC SYNDROME; SEX-DIFFERENCES; FOLLOW-UP; RISK; MORTALITY; OUTPATIENTS; PREVALENCE; HISTORY AB The objective of this study was to determine cardiovascular event rates in diabetic patients and nondiabetic subjects from the REACH Registry with established coronary artery disease, cerebrovascular disease, peripheral arterial disease, or multiple risk factors for atherothrombosis. REACH is an international, prospective, and contemporaneous cohort of patients with >= 3 atherothrombotic risk factors only or established atherothrombotic disease, of which 30,043 have diabetes. The main outcomes after 1-year follow-up were cardiovascular death, myocardial infarction, stroke, major adverse cardiovascular events (MACEs; cardiovascular death, myocardial infarction, or stroke), and MACEs/hospitalization. The MACE rate at 1 year was positively related to the number of atherothrombotic anatomic sites in diabetic patients and nondiabetic subjects, and the rate was higher in those with (3.8%) than without (3.0%, p <0.001) diabetes. Diabetic patients with risk factors only had a lower MACE rate than nondiabetic subjects or diabetic patients with established atherothrombotic disease (2.2% vs 4.0% or 6.0%, respectively, p <0.001 for the 2 comparisons). These differences persisted after adjusting for gender and age. In conclusion, diabetic patients in the REACH Registry have an increased risk of cardiovascular events compared to nondiabetic subjects related to the number of atherothrombotic sites. Although increasing risk, diabetes may not be truly equivalent to previous atherothrombotic events on new cardiovascular event rates. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:667-671) C1 [Krempf, Michel] Inst Thorax, INSERM, UMR915, Nantes, France. [Krempf, Michel] Univ Nantes, CHU, Nantes, France. [Steg, Gabriel] Univ Paris 07, INSERM, U698, Ctr Hosp Bichat Claude, Paris, France. [Pasquet, Blandine] Univ Paris 07, Dept Epidemiol, Hop Bichat Claude Bernard, Paris, France. [Parhofer, Klaus G.] Univ Munich, Klinikum Grosshadern, Dept Internal Med 2, D-8000 Munich, Germany. [Roether, Joachim] Hannover Med Sch, Klinikum Minden, Minden, Germany. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med, Kanagawa 2591100, Japan. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ohman, Magnus] Duke Clin Res Inst, Durham, NC USA. [Ohman, Magnus] Duke Univ, Med Ctr, Durham, NC USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Krempf, M (reprint author), Inst Thorax, INSERM, UMR915, Nantes, France. EM nadine.denoual@univ-nantes.fr FU Sanofi-Aventis (Paris, France); Bristol-Myers Squibb (Paris, France); Waksman Foundation (Tokyo, Japan) FX The REACH Registry is sponsored by Sanofi-Aventis (Paris, France), Bristol-Myers Squibb (Paris, France), and the Waksman Foundation (Tokyo, Japan). NR 20 TC 24 Z9 26 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2010 VL 105 IS 5 BP 667 EP 671 DI 10.1016/j.amjcard.2009.10.048 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 602KD UT WOS:000278137100015 PM 20185014 ER PT J AU Gritli, S Ben Salah, M Shili, A Robson, CD Ferjaoui, M Hendaoui, L Belhani, A Baltagi-Ben Jilani, S Gusella, JF MacRae, CA AF Gritli, Sami Ben Salah, Mamia Shili, Abdessalem Robson, Caroline D. Ferjaoui, Mohamed Hendaoui, Lotfi Belhani, Ali Baltagi-Ben Jilani, Sarrah Gusella, James F. MacRae, Calum A. TI Association of the Long QT Syndrome With Goiter and Deafness SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FAMILIAL EUTHYROID GOITER; CONGENITAL DEAFNESS; PENDRED-SYNDROME; ELECTROCARDIOGRAPHIC ABNORMALITIES; VENTRICULAR REPOLARIZATION; MENTAL-RETARDATION; THYROID-FUNCTION; LINKAGE; VARIABILITY; DELETION AB We report on the long QT syndrome occurring in conjunction with nontoxic multinodular goiter and sensorineural deafness in several siblings of a large family. Autosomal and X-linked recessive and dominant modes of inheritance are possible for the different phenotypes. The affected family members had various phenotype combinations, suggesting variable expressivity and incomplete penetrance. (C) 2010 Published by Elsevier Inc. (Am J Cardiol 2010;105:681-686) C1 [Gritli, Sami; MacRae, Calum A.] Massachusetts Gen Hosp, Dev Biol Lab, Cardiovasc Res Ctr, Charlestown, MA USA. [Gritli, Sami; MacRae, Calum A.] Harvard Univ, Sch Med, Charlestown, MA USA. [Gritli, Sami; Belhani, Ali] Hop Mongi Slim, Serv Cardiol, La Marsa, Tunisia. [Gritli, Sami; Baltagi-Ben Jilani, Sarrah] Hop Charles Nicolle, Dept Pathol, Div Genet Immunol & Cell Biol, Tunis, Tunisia. [Gritli, Sami; Gusella, James F.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Gritli, Sami; Gusella, James F.] Harvard Univ, Sch Med, Boston, MA USA. [Ben Salah, Mamia; Ferjaoui, Mohamed] Hop Charles Nicolle, Serv Otorhinolaryngol, Tunis, Tunisia. [Shili, Abdessalem] Inst Natl Agron, Biol Marine Lab, Tunis, Tunisia. [Robson, Caroline D.] Childrens Hosp, Div Neuroradiol, Boston, MA 02115 USA. [Hendaoui, Lotfi] Hop Mongi Slim, Serv Imagerie Med, La Marsa, Tunisia. RP Gritli, S (reprint author), Massachusetts Gen Hosp, Dev Biol Lab, Cardiovasc Res Ctr, Charlestown, MA USA. EM gritli@helix.mgh.harvard.edu OI Robson, Caroline/0000-0001-5592-249X NR 28 TC 1 Z9 1 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2010 VL 105 IS 5 BP 681 EP 686 DI 10.1016/j.amjcard.2009.10.034 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 602KD UT WOS:000278137100018 PM 20185017 ER PT J AU Dal Cin, P Aster, JC DeAngelo, DJ AF Dal Cin, Paola Aster, Jon C. DeAngelo, Daniel J. TI When to Go FISHing SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material ID IN-SITU HYBRIDIZATION; MYELODYSPLASTIC-SYNDROME PATIENTS; CONVENTIONAL CYTOGENETICS; DELETION; 5Q C1 [Dal Cin, Paola; Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dal Cin, Paola; Aster, Jon C.; DeAngelo, Daniel J.] Harvard Univ, Sch Med, Boston, MA USA. RP Dal Cin, P (reprint author), Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAR PY 2010 VL 133 IS 3 BP 351 EP 353 DI 10.1309/AJCPUD3WU1NIUKCJ PG 3 WC Pathology SC Pathology GA 557RM UT WOS:000274687800001 PM 20154272 ER PT J AU Paulus, JK Asomaning, K Kraft, P Johnson, BE Lin, XH Christiani, DC AF Paulus, Jessica K. Asomaning, Kofi Kraft, Peter Johnson, Bruce E. Lin, Xihong Christiani, David C. TI Parity and Risk of Lung Cancer in Women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE lung neoplasms; parity; reproduction; smoking; women ID ESTROGEN-RECEPTOR-BETA; REPRODUCTIVE FACTORS; CIGARETTE-SMOKING; UNITED-STATES; POSTMENOPAUSAL WOMEN; PROSPECTIVE COHORT; HORMONAL FACTORS; SEX-DIFFERENCES; BREAST-CANCER; CHINESE WOMEN AB Patterns of lung cancer incidence suggest that gender-associated factors may influence lung cancer risk. Given the association of parity with risk of some women's cancers, the authors hypothesized that childbearing history may also be associated with lung cancer. Women enrolled in the Lung Cancer Susceptibility Study at Massachusetts General Hospital (Boston, Massachusetts) between 1992 and 2004 (1,004 cases, 848 controls) were available for analysis of the association between parity and lung cancer risk. Multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. After results were controlled for age and smoking history, women with at least 1 child had 0.71 times the odds of lung cancer as women without children (odds ratio = 0.71, 95% confidence interval: 0.52, 0.97). A significant linear trend was found: Lung cancer risk decreased with increasing numbers of children (P < 0.001). This inverse association was stronger in never smokers (P = 0.12) and was limited to women over age 50 years at diagnosis (P = 0.17). Age at first birth was not associated with risk. The authors observed a protective association between childbearing and lung cancer, adding to existing evidence that reproductive factors may moderate lung cancer risk in women. C1 [Paulus, Jessica K.; Kraft, Peter; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Asomaning, Kofi; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Kraft, Peter; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Paulus, JK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM jpaulus@hsph.harvard.edu FU National Institutes of Health [R01CA74386, T32ES07069, P50 CA 090578] FX This study was supported by National Institutes of Health grants R01CA74386, T32ES07069, and P50 CA 090578. NR 46 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 2010 VL 171 IS 5 BP 557 EP 563 DI 10.1093/aje/kwp441 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 558YY UT WOS:000274786500006 PM 20123687 ER PT J AU Laine, L Spiegel, B Rostom, A Moayyedi, P Kuipers, EJ Bardou, M Sung, J Barkun, AN AF Laine, Loren Spiegel, Brennan Rostom, Alaa Moayyedi, Paul Kuipers, Ernst J. Bardou, Marc Sung, Joseph Barkun, Alan N. TI Methodology for Randomized Trials of Patients With Nonvariceal Upper Gastrointestinal Bleeding: Recommendations From an International Consensus Conference SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID ENDOSCOPIC THERAPY; PEPTIC-ULCER; HEMORRHAGE; MULTICENTER; PANTOPRAZOLE; PREVENTION; INFUSION; BLOOD AB The aim of this document is to provide a methodological framework for the design, performance, analysis, interpretation, and communication of randomized trials that assess management of patients with nonvariceal upper gastrointestinal bleeding. Literature searches were performed and an iterative process with electronic and face-to-face meetings was used to achieve consensus among panel members as part of an International Consensus Conference on Nonvariceal Upper Gastrointestinal Bleeding. Recommendations of the panel include the following. Randomized trials must explicitly state their primary hypothesis. A nonmanipulable randomization schedule with concealed allocation should be used. Stratification (e.g., for age and stigmata of hemorrhage) may be considered, especially in smaller studies. The patient and personnel providing care or recording information should be blinded. Inclusion criteria should be overt bleeding with endoscopy performed within 24 h or less. One type of lesion (e.g., ulcer) should be studied with stigmata to be included predefined. Use of placebo/no therapy vs. active controls depends on current standard practice. Standardizing study and key non-study interventions should ensure uniform provision of interventions. Criteria for repeat endoscopy and subsequent interventions should be predefined. The primary end point should be further bleeding (persistent and recurrent bleeding) with primary assessment at 7 days; mortality, with primary assessment at 30 days, would be appropriate in very large trials. Sample size calculation based on assumptions regarding primary end point results with regard to study intervention and control must be provided, and all patients enrolled must be accounted for. In general, the primary population for analysis is all patients randomized, although a per-protocol population may be used if this is the more conservative approach (e.g., equivalence study). C1 [Laine, Loren] Univ So Calif, Div Gastrointestinal & Liver Dis, Keck Sch Med, Los Angeles, CA 90033 USA. [Spiegel, Brennan] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Spiegel, Brennan] VA Greater Los Angeles Healthcare Syst, Div Digest Dis, Los Angeles, CA USA. [Rostom, Alaa] Univ Calgary, Div Gastroenterol, Calgary, AB, Canada. [Moayyedi, Paul] McMaster Univ, Med Ctr, Div Gastroenterol, Hamilton, ON, Canada. [Kuipers, Ernst J.] Erasmus MC Univ Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands. [Kuipers, Ernst J.] Erasmus MC Univ Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Bardou, Marc] CHU Dijon, Ctr Invest Clin, Dijon, France. [Sung, Joseph] Chinese Univ Hong Kong, Inst Digest Dis, Shatin, Hong Kong, Peoples R China. [Barkun, Alan N.] McGill Univ, Div Gastroenterol, Montreal, PQ, Canada. RP Laine, L (reprint author), Univ So Calif, Div Gastrointestinal & Liver Dis, Keck Sch Med, 2025 Zonal Ave, Los Angeles, CA 90033 USA. EM llaine@usc.edu RI Hossain, Sarah /C-7332-2009; Moayyedi, Paul/M-6178-2014 OI Hossain, Sarah /0000-0003-1355-0979; Moayyedi, Paul/0000-0002-3616-9292 FU Canadian Association of Gastroenterology; European Association for Gastroenterology and Endoscopy; Asian Pacific Society of Digestive Endoscopy; Canadian Institutes of Health Research, Institute of Diabetes, Metabolism and Nutrition; AstaZeneca Molndal; Abbott Canada; Olympus Canada FX This work was supported by the Canadian Association of Gastroenterology; the European Association for Gastroenterology and Endoscopy; the Asian Pacific Society of Digestive Endoscopy; the Canadian Institutes of Health Research, Institute of Diabetes, Metabolism and Nutrition; and arm's length contributions to the above sponsoring societies from AstaZeneca Molndal, Abbott Canada, and Olympus Canada. NR 29 TC 18 Z9 19 U1 0 U2 3 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 MAR PY 2010 VL 105 IS 3 BP 540 EP 550 DI 10.1038/ajg.2009.702 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 567PE UT WOS:000275458300012 PM 20029415 ER PT J AU O'Neil, CE Nicklas, TA Kleinman, R AF O'Neil, Carol E. Nicklas, Theresa A. Kleinman, Ronald TI Relationship Between 100% Juice Consumption and Nutrient Intake and Weight of Adolescents SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE 100% Juice Intake; Dietary Adequacy; Weight; Adolescents ID FRUIT JUICE; ENERGY-INTAKE; VEGETABLE CONSUMPTION; BEVERAGE CONSUMPTION; CHILDRENS GROWTH; AGED CHILDREN; UNITED-STATES; OBESITY; ASSOCIATION; OVERWEIGHT AB Purpose. This study investigated the associations among 100% juice consumption, nutrient intake, and measures of weight in adolescents. Design. A cross-sectional secondary analysis of data from adolescents aged 12 to 18 Years (n = 3939) participating in, the National Health and Nutrition Examination Survey 1999-2002 was conducted to assess nutrient awl weight in categories of 100% juice consumption. Methods. Least square means and logistic regression analyses were generated, and were adjusted for gender, age, ethnicity, and energy intake. Analyses were Bonferroni corrected with an effective p value of .0125. Results. Twenty-eight percent of adolescents (51% male, 42% Hispanic, 25% non-Hispanic while, 29% non-Hispanic black) consumed 100% juice the day of the recall. the mean amount of 100% juice consumed was 3.7 ounces (2.2% of energy intake). Compared with non-juice consumers, carbohydrate, fiber, vitamins C and B6, folate, potassium, copper, magnesium, and iron intakes of juice consumers were higher, and intakes of fat and saturated fatty acids were lower. Those consuming greater than 6 ounces of juice consumed more servings of fruit and less discretionary fat and added sugar than nonconsumers. No differences were found in weight by juice consumption group. Conclusion. In conclusion, when compared with non-juice consumers, adolescents consuming 100% juice did not show mean increased weight measures. Juice provided valuable nutrients, and consumption was associatd with lower intakes of total fat, saturated fatty acids, discretionary fat, and added surgars and with higher intakes of whole fruit; however, consumption was not associated with decreased intake of milk, meal, or grains. (Am J Health promot 2010;24[4]:231-237.) C1 [Nicklas, Theresa A.] Baylor Univ, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX 77030 USA. [O'Neil, Carol E.] Louisiana State Univ, AgCtr, Baton Rouge, LA 70803 USA. [Kleinman, Ronald] Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA USA. RP Nicklas, TA (reprint author), Baylor Univ, Dept Pediat, Childrens Nutr Res Ctr, 1100 Bates Ave, Houston, TX 77030 USA. EM tnicklas@bcm.unc.edu NR 40 TC 24 Z9 25 U1 1 U2 8 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD MAR-APR PY 2010 VL 24 IS 4 BP 231 EP 237 DI 10.4278/ajhp.080603-QUAN-76 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 572DA UT WOS:000275806000002 PM 20232604 ER PT J AU Jacobs, NL Holtan, SG Porrata, LF Markovic, SN Tefferi, A Steensma, DP AF Jacobs, Nisha L. Holtan, Shernan G. Porrata, Luis F. Markovic, Svetomir N. Tefferi, Ayalew Steensma, David P. TI Host immunity affects survival in myelodysplastic syndromes: Independent prognostic value of the absolute lymphocyte count SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID SCORING SYSTEM; BONE-MARROW; T-CELLS; DIFFERENTIATION; TIME AB The prognostic significance of the peripheral blood absolute lymphocyte count (ALC) has been carefully examined in lymphoid malignancies, but the importance of the baseline ALC in chronic myeloid neoplasms is less clear. In a recent analysis of myelodysplastic syndromes (MDS) associated with deletion of chromosome 5q, we observed that an ALC < 1.2 x 10(9) cells/L at diagnosis is independently associated with poorer survival. Clinicopathological data from 503 patients with non-del(5q) MDS evaluated at Mayo Clinic between 1996 and 2007 were reviewed to determine the prognostic impact of ALC at diagnosis in non-del(5q) MDS. Patients with MDS and an ALC at diagnosis >= 1.2x 10(9) (N = 248) experienced a superior overall survival (OS) compared with patients with an ALC < 1.2 x 10(9)/L (N = 255, median OS of 26.6 months versus 18.5 months, P < 0.001, respectively). ALC at diagnosis was an independent predictor for OS when compared with the International Prognostic Scoring System and the WHO-based Prognostic Scoring System. This study suggests that ALC at diagnosis is a prognostic factor for OS in MDS, and argues in favor of further studies to assess the role of host immunity in MDS clinical outcomes. Am. J. Hematol. 85:160-163,2010. (c) 2009 Wiley-Liss, Inc. C1 [Steensma, David P.] Dana Farber Canc Inst, Dept Oncol, Div Hematol Malignancies, Leukemia Grp, Boston, MA 02115 USA. [Jacobs, Nisha L.] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. [Holtan, Shernan G.; Porrata, Luis F.; Markovic, Svetomir N.; Tefferi, Ayalew] Mayo Clin, Grad Sch Med, Div Hematol, Dept Med, Rochester, MN USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Dept Oncol, Div Hematol Malignancies, Leukemia Grp, 44 Binney St,Suite D1B30 Mayer 1B21, Boston, MA 02115 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 NR 22 TC 12 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2010 VL 85 IS 3 BP 160 EP 163 DI 10.1002/ajh.21618 PG 4 WC Hematology SC Hematology GA 568GK UT WOS:000275510100003 PM 20131304 ER PT J AU Castellone, DD Van Cott, EM AF Castellone, Donna D. Van Cott, Elizabeth M. TI Laboratory monitoring of new anticoagulants SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID DIRECT THROMBIN INHIBITORS; CLOTTING TIME; FONDAPARINUX; ASSAY; RIVAROXABAN; ARGATROBAN; WARFARIN; THERAPY AB Maintaining a balance between bleeding and clotting has always been a challenge in treating coagulation disorders. A perturbation in that balance can be associated with substantial morbidity and mortality. As a result, anticoagulant monitoring is extremely important, and inappropriate testing may lead to complications. There are now a variety of new anticoagulant drugs in clinical use including several direct thrombin inhibitors (DTIs), such as argatroban, bivalirudin, and hirudin, as well as a Factor Xa inhibitor, fondaparinux. There are pitfalls associated with some of the currently used laboratory monitoring tests, and newer alternative laboratory monitoring tests have been investigated (Walenga and Hoppensteadt, Semin Thromb Hemost 2004;30:683-695). In addition, laboratory testing can assist with transitioning patients from DTI to warfarin therapy. Am. J. Hematol. 85:185-187, 2010. (c) 2009 Wiley-Liss, Inc. C1 [Castellone, Donna D.] Siemens Healthcare Diagnost, Med Clin & Stat Affairs, Tarrytown, NY 10591 USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Coagulat Lab, Boston, MA 02114 USA. RP Castellone, DD (reprint author), Siemens Healthcare Diagnost, Med Clin & Stat Affairs, 511 Benedict Ave, Tarrytown, NY 10591 USA. EM donna.castellone@siemens.com FU NIH [PHS R01 DK63088, PHS RR-08084, PHS U54 HL070871] FX NIH; PHS R01 DK63088, PHS RR-08084, and PHS U54 HL070871. NR 17 TC 36 Z9 37 U1 0 U2 7 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 MAR PY 2010 VL 85 IS 3 BP 185 EP 187 DI 10.1002/ajh.21607 PG 3 WC Hematology SC Hematology GA 568GK UT WOS:000275510100009 PM 20131309 ER PT J AU Steensma, DP AF Steensma, David P. TI ASH 2009 meeting report - Top 10 clinically oriented abstracts in myelodysplastic syndromes SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; PROGNOSTIC SCORING SYSTEM; ANTITHYMOCYTE GLOBULIN; 5Q DELETION; CHROMOSOME 5Q; PHASE-III; LOW-RISK; LENALIDOMIDE; AZACITIDINE; EFFICACY AB Among the 4,097 abstracts presented orally or in poster format at the December 2009 American Society of Hematology (ASH) annual meeting in New Orleans, LA, 139 abstracts (36 presentations in six oral sessions and 103 posters in three poster sessions) were assigned to the general category of myelodysplastic syndromes (MDS). Here, I summarize and discuss 10 clinically relevant abstracts related to MDS, all of which are published in their entirety in the November 20, 2009 issue of Blood (volume 114, issue 22) and are identified here by their abstract numbers. These 10 abstracts-six oral presentations and four posters-concern prognostic modeling, treatment with hypomethylating agents (azacitidine or decitabine), and therapy with immunomodulatory or immunosuppressive drugs (lenalidomide or alemtuzumab). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Steensma, DP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St,Suite D1B30,Mayer 1B21, Boston, MA 02115 USA. EM david_steesma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 NR 44 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2010 VL 85 IS 3 BP 196 EP 201 PG 6 WC Hematology SC Hematology GA 568GK UT WOS:000275510100019 ER PT J AU Weigelt, JA Lipsky, BA Tabak, YP Derby, KG Kim, M Gupta, V AF Weigelt, John A. Lipsky, Benjamin A. Tabak, Ying P. Derby, Karen G. Kim, Myoung Gupta, Vikas TI Surgical site infections: Causative pathogens and associated outcomes SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Surgical site infection; outcomes research; methicillin-resistant Staphylococcus aureus; hospital mortality; hospital length of stay; hospital costs ID RESISTANT STAPHYLOCOCCUS-AUREUS; ECONOMIC OUTCOMES; UNITED-STATES; SURVEILLANCE; PREVENTION; HOSPITALS; IMPACT; MORTALITY; DISCHARGE; SURGERY AB Background: Surgical site infections (SSIs) are associated with substantial morbidity, mortality, and cost. Few studies have examined the causative pathogens, mortality, and economic burden among patients rehospitalized for SSIs. Methods: From 2003 to 2007, 8302 patients were readmitted to 97 US hospitals with a culture-confirmed SSI. We analyzed the causative pathogens and their associations with in-hospital mortality, length of stay (LOS), and cost. Results: The proportion of methicillin-resistant Staphylococcus aureus (MRSA) significantly increased among culture-positive SSI patients during the study period (16.1% to 20.6%, respectively, P<.0001). MRSA (compared with other) infections had higher raw mortality rates (1.4% vs 0.8%, respectively, P=.03), longer LOS (median, 6 vs 5 days, respectively, P<.0001), and higher hospital costs ($7036 vs $6134, respectively, P<.0001). The MRSA infection risk-adjusted attributable LOS increase was 0.93 days (95% confidence interval [CI]: 0.65-1.21; P<.0001), and cost increase was $1157 (95% CI: $641-$1644; P<.0001). Other significant independent risk factors increasing cost and LOS included illness severity, transfer from another health care facility, previous admission (<30 days), and other polymicrobial infections (P<.05). Conclusion: SSIs caused by MRSA increased significantly and were independently associated with economic burden. Admission illness severity, transfer from another health care setting, and recent hospitalization were associated with higher mortality, increased LOS, and cost. C1 [Weigelt, John A.] Med Coll Wisconsin, Dept Surg, Div Trauma Crit Care, Milwaukee, WI 53226 USA. [Lipsky, Benjamin A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Lipsky, Benjamin A.] Univ Washington, Seattle, WA 98195 USA. [Tabak, Ying P.; Derby, Karen G.; Gupta, Vikas] Cardinal Hlth Clin Res Serv, Marlborough, MA USA. [Kim, Myoung] Ortho McNeil Janssen Sci Affairs LLC, Raritan, NJ USA. RP Weigelt, JA (reprint author), Med Coll Wisconsin, Dept Surg, Div Trauma Crit Care, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM jweigelt@mcw.edu OI Lipsky, Benjamin A./0000-0001-9886-5114 FU OMJUS FX Dr. Weigelt is an advisory board member, on the speaker's bureau, received research support from OMJUS; Dr. Lipsky is an advisory board member and has received research support from OMJUS; Dr. Kim is a current employee of OMJUS; Ms. Derby and Drs. Tabak and Gupta are currently employees of Cardinal Health, Inc. Dr. Lipsky is an employee of the US Government. This paper does not represent the views of the US Government. NR 24 TC 44 Z9 48 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAR PY 2010 VL 38 IS 2 BP 112 EP 120 DI 10.1016/j.ajic.2009.06.010 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 559WR UT WOS:000274859500005 PM 19889474 ER PT J AU Johansen, KL Finkelstein, FO Revicki, DA Gitlin, M Evans, C Mayne, TJ AF Johansen, Kirsten L. Finkelstein, Fredric O. Revicki, Dennis A. Gitlin, Matthew Evans, Christopher Mayne, Tracy J. TI Systematic Review and Meta-analysis of Exercise Tolerance and Physical Functioning in Dialysis Patients Treated With Erythropoiesis-Stimulating Agents SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Review DE Chronic kidney disease; erythropoiesis-stimulating agents; epoetin alfa; exercise tolerance; quality of life ID QUALITY-OF-LIFE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; ANEMIC HEMODIALYSIS-PATIENTS; SICKNESS IMPACT PROFILE; CHRONIC KIDNEY-DISEASE; CORONARY-ARTERY DISEASE; CHRONIC HEART-FAILURE; CHRONIC-RENAL-FAILURE; HEALTH-STATUS MEASURE; MAINTENANCE HEMODIALYSIS AB Background: The role of erythropoiesis-stimulating agents (ESAs) in treating the anemia of chronic kidney disease has been reevaluated in view of recent studies suggesting that the use of these agents may be associated with increased morbidity and mortality. This potential increased risk needs to be weighed against the potential benefit of ESAs in improving various aspects of health-related quality of life, in particular, exercise tolerance and physical functioning. Study Design: A systematic review and meta-analysis of exercise tolerance and physical functioning. Setting & Participants: Adults on maintenance dialysis therapy. Selection Criteria for Studies: Outcomes measured before and after ESA treatment were required. Studies of physical function were required to include at least 25 participants. Intervention: Treatment with any ESA. Outcomes: Exercise tolerance measured using VO2peak (oxygen consumption per minute at the peak workload during the test), duration of exercise, or 6-minute walk distance or physical functioning assessed using >= 1 patient-or clinician-reported outcome measure that included a physical function domain. Results: 28 articles met criteria for inclusion for evaluation of exercise tolerance, and 14 articles, for physical function. Meta-analysis showed a 23.8% increase in VO2peak from before to after erythropoietin therapy initiation (15 studies) and a nonsignificant 8.2% increase comparing a higher with a lower hemoglobin target (3 studies). For physical functioning, 4 studies met criteria for inclusion in the meta-analysis: there was a 10.5% increase in Karnofsky score from before to after erythropoietin therapy initiation. Limitations: Many studies of exercise tolerance did not include control groups. A wide variety of instruments was used to assess physical function. Conclusions: Partial correction of anemia through ESA treatment has a consistent and positive impact on VO2peak. ESA treatment improves patient-and clinician-assessed physical functioning. Am J Kidney Dis 55: 535-548. (C) 2010 by the National Kidney Foundation, Inc. C1 [Johansen, Kirsten L.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Finkelstein, Fredric O.] Yale Univ, Hosp St Raphael, New Haven, CT USA. [Revicki, Dennis A.] United BioSource Corp, Bethesda, MD USA. [Gitlin, Matthew; Mayne, Tracy J.] Amgen Inc, Thousand Oaks, CA USA. [Evans, Christopher] Mapi Values, Boston, MA USA. RP Johansen, KL (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU Amgen Inc. FX This study was conceived by employees of Amgen Inc, which markets ESAs; Dr Gitlin is an employee of Amgen Inc. Dr Mayne formerly was an employee of Amgen Inc. Drs Johansen and Finkelstein have received research support from Amgen Inc. Dr Revicki and his employer United Biosource Corp, as well as Dr Evans and his employer MapiValues, have received consulting fees and research support from Amgen Inc. NR 70 TC 35 Z9 37 U1 3 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2010 VL 55 IS 3 BP 535 EP 548 DI 10.1053/j.ajkd.2009.12.018 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 563DW UT WOS:000275109000017 PM 20133033 ER PT J AU Jolly, SE Burrows, NR Chen, SC Li, SY Jurkovitz, CT Narva, AS Norris, KC Shlipak, MG AF Jolly, Stacey E. Burrows, Nilka Rios Chen, Shu-Cheng Li, Suying Jurkovitz, Claudine T. Narva, Andrew S. Norris, Keith C. Shlipak, Michael G. TI Racial and Ethnic Differences in Albuminuria in Individuals With Estimated GFR Greater Than 60 mL/min/1.73 m(2): Results From the Kidney Early Evaluation Program (KEEP) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Albuminuria; health disparities; Kidney Early Evaluation Program (KEEP); screening ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE VALUES; RENAL-DISEASE; NONDIABETIC INDIVIDUALS; CARDIOVASCULAR EVENTS; GENERAL-POPULATION; AMERICAN-INDIANS; NATIONAL-HEALTH; HEART-FAILURE; UNITED-STATES AB Background: Albuminuria is an important marker for chronic kidney disease and progression to end-stage renal disease in the general population; understanding racial and ethnic differences can help inform efforts to reduce health disparities. We sought to estimate independent associations of race/ethnicity with albuminuria to determine whether observed differences were attributable to known kidney disease risk factors. Methods: This cross-sectional study included 64,161 Kidney Early Evaluation Program (KEEP) participants, 2000-2008, with estimated glomerular filtration rate >= 60 mL/min/1.73 m(2), not on regular dialysis therapy, and without a previous kidney transplant. Albuminuria (urine albumin-creatinine ratio >= 30 mg/g) was examined by self-reported race and ethnicity. Covariates were age, sex, educational level, body mass index, diabetes status or glucose level, hypertension status or blood pressure measurement, smoking status, health insurance status, and geographic region. Results: Albuminuria prevalences were 8% (n = 2,303) in whites, 11% (n = 2,310) in African Americans, 9% (n = 730) in Hispanics, 10% (n = 381) in Asians, and 15% (n = 344) in American Indians/ Alaska Natives. Compared with whites, odds of albuminuria were higher for all groups after multivariate adjustment. Odds were highest for American Indians/Alaska Natives (adjusted OR, 1.93; 95% CI, 1.70-2.20), then Asians (adjusted OR, 1.42; 95% CI, 1.26-1.61), African Americans (adjusted OR, 1.38; 95% CI, 1.29-1.47), and Hispanics (adjusted OR, 1.19; 95% CI, 1.08-1.31). Conclusions: In the KEEP study population, albuminuria prevalence was higher in African Americans, Hispanics, Asians, and American Indians/Alaska Natives than in non-Hispanic whites, suggesting a need for screening for early detection of kidney damage, especially in people at increased risk, in the community primary care setting. Am J Kidney Dis 55(S2):S15-S22. (c) 2010 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Jolly, Stacey E.] Cleveland Clin, Inst Med, Cleveland, OH 44195 USA. [Burrows, Nilka Rios] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Chen, Shu-Cheng; Li, Suying] Minneapolis Med Res Fdn Inc, Chron Dis Res Grp, Minneapolis, MN USA. [Jurkovitz, Claudine T.] Christiana Care Hlth Syst, Ctr Outcomes Res, Newark, DE USA. [Narva, Andrew S.] NIDDK, Bethesda, MD USA. [Norris, Keith C.] Charles R Drew Univ Med & Sci, Dept Internal Med, Los Angeles, CA 90059 USA. [Shlipak, Michael G.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Jolly, SE (reprint author), Cleveland Clin, Inst Med, 9500 Euclid Ave,G10, Cleveland, OH 44195 USA. EM jollys@ccf.org FU National Kidney Foundation Inc; Amgen; Abbott; Novartis; Siemens; Genentech; Genzyme; Nephroceuticals; Pfizer; LifeScan; Suplena; National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK 066488] FX The KEEP is a program of the National Kidney Foundation Inc and is supported by Amgen, Abbott, Novartis, Siemens, Genentech, Genzyme, Nephroceuticals, Pfizer, LifeScan, and Suplena. Dr Shlipak's work was supported by the American Heart Association Established Investigator Award and R01 DK 066488 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 41 TC 18 Z9 19 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2010 VL 55 IS 3 SU 2 BP S15 EP S22 DI 10.1053/j.ajkd.2009.09.034 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 559WU UT WOS:000274859800003 PM 20172444 ER PT J AU Copeland, LA Berg, GD Johnson, DM Bauer, RL AF Copeland, Laurel A. Berg, Gregory D. Johnson, Donna M. Bauer, Richard L. TI An Intervention for VA Patients With Congestive Heart Failure SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID PROPENSITY SCORE; READMISSION; POPULATION; CARDIOMYOPATHY; MANAGEMENT; MORTALITY; ADMISSION; OUTCOMES; RISK; CARE AB Objective: To assess the effect of a telephone intervention to improve quality of life among patients with congestive heart failure (CHF). Study Design: Prospective randomized study. Methods: Single-site recruitment of 458 patients using Veterans Health Administration care into a randomized controlled trial with a 1-year pre-intervention data collection period and a 1-year intervention and follow-up period. To compensate for imbalanced study groups, propensity scores were included in adjusted models of quality of life, satisfaction with care, inpatient utilization, survival, and costs of care. Results: Patients aged 45 to 95 years participated in the study; 22% were of Hispanic race/ethnicity, and 7% were African American. All but 5 were male, consistent with the older population among veterans. At baseline, 40% were in Goldman Specific Activity Scale class I, 42% were in class III, 6% were in class II or IV, and 12% were unclassified. Patients scored a mean (SD) of 14 (1.5) points below the norm on the physical component score. After the yearlong intervention, no differences in clinical outcomes were noted between the intervention group and the control group. The CHF-related costs were higher for the intervention group, as were overall costs that included the cost of the intervention. Intervention group patients reported better compliance with weight monitoring and exercise recommendations. Conclusions: A risk-stratified intervention for patients with CHF resulted in potential behavioral improvements but no survival benefit. A high-cost high-intensity intervention may be required to improve survival for patients with CHF. Inclusion of the costs of interventions is recommended for future researchers. (Am J Manag Care. 2010; 16(3): 158-165) C1 [Copeland, Laurel A.; Bauer, Richard L.] S Texas Vet Hlth Care Syst, Dept Vet Affairs, VERDICT Res Ctr, San Antonio, TX 78229 USA. [Copeland, Laurel A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Bauer, Richard L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Berg, Gregory D.; Johnson, Donna M.] McKesson Corp, Broomfield, CO USA. RP Copeland, LA (reprint author), S Texas Vet Hlth Care Syst, Dept Vet Affairs, VERDICT Res Ctr, 7400 Merton Minter 11C6, San Antonio, TX 78229 USA. EM laurel.copeland@va.gov OI Copeland, Laurel/0000-0002-9478-0209 FU Veterans Health Administration, Health Services Research and Development; Office of the Chief of Staff and the VERDICT Research Center, South Texas Veterans Health Care System; McKesson Corporation; Veterans Health Administration [MRP-05-145, IIR-05-326] FX This study was supported by the Veterans Health Administration, Health Services Research and Development Program; by the Office of the Chief of Staff and the VERDICT Research Center, South Texas Veterans Health Care System; and by the McKesson Corporation, which developed the intervention tested.; Dr Copeland was supported by Health Services Research and Development Program career development grants MRP-05-145 and IIR-05-326 from the Veterans Health Administration. NR 28 TC 12 Z9 12 U1 0 U2 3 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 MAR PY 2010 VL 16 IS 3 BP 158 EP 165 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 567XY UT WOS:000275483400001 PM 20225911 ER PT J AU Pevnick, JM Asch, SM Adams, JL Mattke, S Patel, MH Ettner, SL Bell, DS AF Pevnick, Joshua M. Asch, Steven M. Adams, John L. Mattke, Soeren Patel, Mihir H. Ettner, Susan L. Bell, Douglas S. TI Adoption and Use of Stand-Alone Electronic Prescribing in a Health Plan-Sponsored Initiative SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID MEDICAL-RECORDS; PHYSICIANS; CARE; QUALITY; ERRORS AB Objectives: To quantify rates of stand-alone e-prescribing (SEP) adoption and use among primary care physicians (PCPs) participating in a SEP initiative and to determine which physician and patient characteristics were associated with higher rates of each. Study Design: Using records from an insurer-led SEP initiative, we compared the characteristics of 297 PCPs who adopted SEP through the initiative with the characteristics of 1892 eligible PCPs who did not. Among 297 adopters, we studied the extent of SEP use. Methods: Dependent variables included each physician's adoption of SEP and his or her e-prescribing use ratio (the ratio of electronic prescriptions to pharmacy claims in the same period). Independent variables included characteristics of PCPs (specialty, practice size, and prescribing volume) and their patients (patient age, sex, race/ethnicity, and household income). Results: Solo practitioners, pediatricians, and physicians with more patients from predominantly African American zip codes were under-represented among SEP adopters. The mean (SD) e-prescribing use ratio among adopters was 0.23 (0.28). Twenty percent of physicians maintained e-prescribing use ratios above 0.50. Available physician characteristics explained little of the variance in use, but physicians in smaller practices had greater use (P = .02). Conclusions: Certain categories of physicians may need more tailored incentives to adopt SEP. On average, adopters used the SEP system for only about one-quarter of their prescriptions. Some adopters achieved high levels of SEP use, and further research is needed to elucidate the factors that enabled this. (Am J Manag Care. 2010; 16(3): 182-189) C1 [Pevnick, Joshua M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Pevnick, Joshua M.; Asch, Steven M.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven M.; Adams, John L.; Bell, Douglas S.] RAND Hlth, Santa Monica, CA USA. [Mattke, Soeren] RAND Hlth, Boston, MA USA. [Patel, Mihir H.] Horizon Blue Cross Blue Shield New Jersey, Newark, NJ USA. [Asch, Steven M.; Ettner, Susan L.; Bell, Douglas S.] Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. RP Pevnick, JM (reprint author), Cedars Sinai Med Ctr, 8700 Beverly Blvd,Rm B113, Los Angeles, CA 90048 USA. EM jpevnick@gmail.com RI Bell, Douglas/G-6702-2013 OI Bell, Douglas/0000-0002-5063-8294 FU Agency for Healthcare Research and Quality [1U18HS016391-01]; Department of Veterans Affairs FX This project was funded by grant 1U18HS016391-01 from the Agency for Healthcare Research and Quality as part of a larger set of e-prescribing pilot studies. This work was also supported by a health services research and development fellowship from the Department of Veterans Affairs (Dr Pevnick). NR 22 TC 10 Z9 10 U1 1 U2 2 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 MAR PY 2010 VL 16 IS 3 BP 182 EP 189 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 567XY UT WOS:000275483400003 PM 20225913 ER PT J AU Kaplan, L Foster, R Shen, YP Parry, DM McMaster, ML O'Leary, MC Gusella, JF AF Kaplan, Lee Foster, Rosemary Shen, Yiping Parry, Dilys M. McMaster, Mary L. O'Leary, Melanie Collins Gusella, James F. TI Monozygotic Twins Discordant for Neurofibromatosis 1 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE neurofibromatosis type 1; monozygotic twins; discordance; post-zygotic mutation ID SEGMENTAL NEUROFIBROMATOSIS; NF1 GENE; TYPE-1 NF1; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; NONSENSE MUTATION; MOSAICISM; POLYMORPHISMS; METHYLATION; FREQUENCY; SEQUENCE AB We present monozygotic twins discordant for the autosomal dominant disorder neurofibromatosis type 1 (NF1). The affected twin was diagnosed with NF1 at age 12, based upon accepted clinical criteria for the disorder. Both twins were re-examined at ages 35 and 57, at which times the unaffected twin continued to show no clinical manifestations of NF1. Short tandem repeat marker (STR) genotyping at 10 loci on chromosome 17 and 10 additional loci dispersed across the genome revealed identical genotypes for the twins, confirming their monozygosity. The affected twin has three children, two of whom also have NF1, while the unaffected twin has two children, both unaffected. Using lymphoblastoid, fibroblast, and buccal cell samples collected from both twins and from other family members in three generations, we discovered a pathogenic nonsense mutation in exon 40 of the NF1 gene. This mutation was found in all cell samples from the affected twin and her affected daughter, and in lymphoblastoid and buccal cells but not fibroblasts from the unaffected twin. We also found a novel non-synonymous change in exon 16 of the NF1 gene that was transmitted from the unaffected mother to both twins and co-segregated with the pathogenic mutation in the ensuing generation. All cells from the twins were heterozygous for this apparent exon 16 polymorphism and for single nucleotide polymorphisms (SNPs) within 2.5 kb flanking the site of the exon 40 nonsense mutation. This suggests that the NF1 gene of the unaffected twin differed in the respective lymphoblastoid cells and fibroblasts only at the mutation site itself, making post-zygotic mutation leading to mosaicism the most likely mechanism of phenotypic discordance. Although the unaffected twin is a mosaic, the distribution of the mutant allele among different cells and tissues appears to be insufficient to cause overt clinical manifestations of NF1. (C) 2010 Wiley-Liss, Inc. C1 [Kaplan, Lee; Shen, Yiping; O'Leary, Melanie Collins; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kaplan, Lee; Shen, Yiping; O'Leary, Melanie Collins; Gusella, James F.] Harvard Univ, Sch Med, Ctr Neurofibromatosis & Allied Disorders, Boston, MA USA. [Foster, Rosemary] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Foster, Rosemary] Ctr Regenerat Med, Boston, MA USA. [Foster, Rosemary] Harvard Stem Cell Inst, Boston, MA USA. [Shen, Yiping] Childrens Hosp, DNA Diagnost Lab, Dept Lab Med, Boston, MA 02115 USA. [Parry, Dilys M.; McMaster, Mary L.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, CPZN-5830,185 Cambridge St, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu FU NINDS [NS22224, NS24279]; Neurofibromatosis, Inc., Northeast; S. Sydney De Young Foundation FX The authors would like to thank the family members who have contributed samples and time in the clinic so that we could perform this research project. Also we thank Mary Anne Anderson and the CHGR Cell Culture Resource for making the stable cell lines, James Mull for technical assistance, and Tammy Gillis and the CHGR Genomics Resource for DNA sequence analysis. Funded by grants from the NINDS (NS22224, NS24279), Neurofibromatosis, Inc., Northeast, and the S. Sydney De Young Foundation. NR 43 TC 20 Z9 20 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAR PY 2010 VL 152A IS 3 BP 601 EP 606 DI 10.1002/ajmg.a.33271 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 576OV UT WOS:000276155200010 PM 20186797 ER PT J AU Wan, ES Pober, BR Washko, GR Raby, BA Silverman, EK AF Wan, Emily S. Pober, Barbara R. Washko, George R. Raby, Benjamin A. Silverman, Edwin K. TI Pulmonary Function and Emphysema in Williams-Beuren Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE elastin; emphysema; pulmonary function tests; Williams syndrome ID AUTOSOMAL-DOMINANT INHERITANCE; CUTIS LAXA; ELASTIN; DISEASE; LUNG; HEMIZYGOSITY; DELETIONS; MUTATION; RISK; GENE AB Williams-Beuren syndrome (WBS) is caused by a submicroscopic deletion on chromosome 7q11.23 that encompasses the entire elastin (ELN) gene. Elastin, a key component of elastic fibers within the lung, is progressively destroyed in emphysema. Defects in the elastin gene have been associated with increased susceptibility towards developing chronic obstructive pulmonary disease (COPD) and emphysema in both humans and mice. We postulate that hemizygosity at the elastin gene locus may increase susceptibility towards the development of COPD and emphysema in subjects with WBS. We describe an adult subject with WBS who was a lifelong non-smoker and was found to have moderate emphysema. We also examined the pulmonary function of a separate cohort of adolescents and young adults with WBS. Although no significant spirometric abnormalities were identified, a significant proportion of subjects reported respiratory symptoms. Thus, while significant obstructive disease does not appear to be common in relatively young adults with WBS, subclinical emphysema and lung disease may exist which possibly could worsen with advancing age. Further investigation may elucidate the pathogenesis of non-smoking-related emphysema. (C) 2010 Wiley-Liss, Inc. C1 [Wan, Emily S.; Raby, Benjamin A.; Silverman, Edwin K.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Wan, Emily S.; Washko, George R.; Raby, Benjamin A.; Silverman, Edwin K.] Brigham & Womens Hosp, Dept Med, Pulm & Crit Care Div, Boston, MA 02115 USA. [Pober, Barbara R.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Silverman, EK (reprint author), 181 Longwood Ave,4th Floor, Boston, MA 02115 USA. EM ed.silverrnan@channing.harvard.edu FU NHLBI NIH HHS [T32 HL007427-19, R01 HL075478-06, R01 HL075478] NR 25 TC 8 Z9 8 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAR PY 2010 VL 152A IS 3 BP 653 EP 656 DI 10.1002/ajmg.a.33300 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 576OV UT WOS:000276155200017 PM 20186780 ER PT J AU Brown, AB Biederman, J Valera, EM Doyle, AE Bush, G Spencer, T Monuteaux, MC Mick, E Whitfield-Gabrieli, S Makris, N LaViolette, PS Oscar-Berman, M Faraone, SV Seidman, LJ AF Brown, Ariel B. Biederman, Joseph Valera, Eve M. Doyle, Alysa E. Bush, George Spencer, Thomas Monuteaux, Michael C. Mick, Eric Whitfield-Gabrieli, Susan Makris, Nikos LaViolette, Peter S. Oscar-Berman, Marlene Faraone, Stephen V. Seidman, Larry J. TI Effect of Dopamine Transporter Gene (SLC6A3) Variation on Dorsal Anterior Cingulate Function in Attention-Deficit/Hyperactivity Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE dopamine transporter gene; functional magnetic resonance imaging; genetics; adhd; anterior cingulate ID DEFICIT HYPERACTIVITY DISORDER; MULTISOURCE INTERFERENCE TASK; GENOTYPE INFLUENCES; WORKING-MEMORY; HUMAN BRAIN; ADULT ADHD; METHYLPHENIDATE; CHILDREN; METAANALYSIS; ASSOCIATION AB Although attention-deficit/hyperactivity disorder (ADHD) is associated both with brain alterations in attention and executive function (EF) circuitry and with genetic variations within the dopamine system (including the dopamine transporter gene [SLC6A3]), few studies have directly investigated how genetic variations are linked to brain alterations. We sought to examine how a polymorphism in the 3' untranslated region (UTR) of SLC6A3, associated with ADHD in meta-analysis, might contribute to variation in dorsal anterior cingulate cortex (dACC) function in subjects with ADHD. We collected fMRI scans of 42 individuals with ADHD, all of European descent and over the age of 17, while they performed the multi-source interference task (MSIT), a cognitive task shown to activate dACC. SLC6A3 3'UTR variable number tandem repeat (VNTR) polymorphisms were genotyped and brain activity was compared for groups based on allele status. ADHD individuals homozygous for the 10R allele showed significant hypoactivation in the left dACC compared to 9R-carriers. Exploratory analysis also showed trends toward hypoactivation in the 10R homozygotes in left cerebellar vermis and right lateral prefrontal cortex. Further breakdown of genotype groups showed similar activation in individuals heterozygous and homozygous for the 911 allele. Alterations in activation of attention and EF networks found previously to be involved in ADHD are likely influenced by SLC6A3 genotype. This genotype may contribute to heterogeneity of brain alterations found within ADHD samples. (C) 2009 Wiley-Liss, Inc. C1 [Brown, Ariel B.; Biederman, Joseph; Valera, Eve M.; Doyle, Alysa E.; Spencer, Thomas; Monuteaux, Michael C.; Mick, Eric; LaViolette, Peter S.; Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Adult ADHD, Boston, MA 02114 USA. [Brown, Ariel B.; Biederman, Joseph; Valera, Eve M.; Doyle, Alysa E.; Spencer, Thomas; Monuteaux, Michael C.; Mick, Eric; LaViolette, Peter S.; Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Makris, Nikos] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Brown, Ariel B.; Oscar-Berman, Marlene] Boston Univ, Sch Med, Div Grad Med Sci, PhD Program Behav Neurosci, Boston, MA 02118 USA. [Valera, Eve M.; Bush, George] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Program, Boston, MA 02114 USA. [Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Makris, Nikos] Harvard Univ, Sch Med, Dept Radiol Serv, Boston, MA USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Oscar-Berman, Marlene] US Dept Vet Affairs Healthcare Syst, Boston, MA USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat,Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Publ Psychiat Div, Boston, MA 02115 USA. RP Brown, AB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Pediat Psychopharmacol, East Campus,149 13th St,Rm 2603, Charlestown, MA 02129 USA. EM ariel@nmr.mgh.harvard.edu OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH [MH 62152, MH 57934, MH 071535]; US Department of Health and Human Services; NIAAA [R01-AA07112, K05-AA00219]; National Alliance for Research oil Schizophrenia; Janssen Pharmaceuticals; US Department of Veterans Affairs; March of Dimes Foundation; Mental Illness and Neuroscience Discovery (MIND) Institute; Kimmerly-Neil Fund; Pediatric Psychopharmacology Counci; National Center for Research Resources [P41RR14075] FX Grant sponsor: NIMH; Grant Numbers: MH 62152, MH 57934, MH 071535; Grant sponsor: US Department of Health and Human Services; Grant sponsor: NIAAA; Grant Numbers: R01-AA07112, K05-AA00219; Grant sponsor: National Alliance for Research oil Schizophrenia and Depression Distinguished Investigator Award; Grant sponsor: Janssen Pharmaceuticals; Grant sponsor: Medical Research Service of the US Department of Veterans Affairs; Grant sponsor: March of Dimes Foundation; Grant sponsor: Mental Illness and Neuroscience Discovery (MIND) Institute; Grant sponsor: Kimmerly-Neil Fund for the Study of Cognition and Psychiatric Disorders in Children; Grant sponsor: Pediatric Psychopharmacology Council Fund; Grant sponsor: National Center for Research Resources; Grant number: P41RR14075. NR 59 TC 24 Z9 25 U1 2 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR PY 2010 VL 153B IS 2 BP 365 EP 375 DI 10.1002/ajmg.b.31022 PG 11 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 566NI UT WOS:000275377900002 PM 19676101 ER PT J AU Bekris, LM Galloway, NM Montine, TJ Schellenberg, GD Yu, CE AF Bekris, Lynn M. Galloway, Nichole M. Montine, Thomas J. Schellenberg, Gerard D. Yu, Chang-En TI APOE mRNA and Protein Expression in Postmortem Brain Are Modulated by an Extended Haplotype Structure SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE Alzheimer's disease; APOE; post-mortem brain; TOMM40 ID APOLIPOPROTEIN-E GENE; AMYLOID PRECURSOR PROTEIN; ONSET ALZHEIMERS-DISEASE; TRANSGENIC MICE; E GENOTYPE; MITOCHONDRIAL DYSFUNCTION; PROMOTER POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; ALLELIC EXPRESSION; REGULATORY REGION AB Currently the epsilon 4 allele of the apolipoprotein E gene (APOE) is the strongest genetic risk factor for late onset Alzheimer's disease (AD). However, inheritance of the APOE epsilon 4 allele is not necessary or sufficient for the development of AD. Genetic evidence suggests that multiple loci in a 70 kb region surrounding APOE are associated with AD risk. Even though these loci could represent surrogate markers in linkage disequilibrium with APOE epsilon 4 allele, they could also contribute biological effects independent of the APOE epsilon 4 allele. Our previous study identified multiple SNPs upstream from APOE that are associated with cerebrospinal fluid apoE levels, suggesting that a haplotype structure proximal to APOE can influence apoE expression. In this study, we examined apoE expression in human post-mortem brain (PMB), and constructed chromosome-phase-separated haplotypes of the APOE proximal region to evaluate their effect on PMB apoE expression. ApoE protein expression was found to differ among AD brain regions and to differ between AD and control hippocampus. in addition, an extended APOE proximal haplotype structure, spanning from the TOMM40 gene to the APOE promoter, may modulate apoE expression in a brain region-specific manner and may influence AD disease status. In conclusion, this haplotype-phenotype analysis of apoE expression in PMB suggests that either; (1) the cis-regulation of APOE expression levels extends far upstream of the APOE promoter or (2) an APOE epsilon 4 allele independent mechanism involving the TOMM40 gene plays a role in the risk of AD. (C) 2009 Wiley-Liss, Inc. C1 [Bekris, Lynn M.; Galloway, Nichole M.; Yu, Chang-En] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Bekris, Lynn M.; Yu, Chang-En] Univ Washington, Dept Med, Seattle, WA USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Bekris, LM (reprint author), 1660 S Colombian Way,Box 358280 GRECC S182B, Seattle, WA 98108 USA. EM lbekris@u.washington.edu FU Veterans Affairs Biomedical Laboratory Research Development Merit Review; National Institutes of Health [P50 AG00536] FX Grant sponsor: Veterans Affairs Biomedical Laboratory Research Development Merit Review; Grant sponsor: National Institutes of Health; Grant Number: P50 AG00536. NR 48 TC 32 Z9 32 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR PY 2010 VL 153B IS 2 BP 409 EP 417 DI 10.1002/ajmg.b.30993 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 566NI UT WOS:000275377900006 PM 19554612 ER PT J AU Sanchez-Mora, C Ribases, M Ramos-Quiroga, JA Casas, M Bosch, R Boreatti-Hummer, A Heine, M Jacob, CP Lesch, KP Fasmer, OB Knappskog, PM Kooij, JJS Kan, C Buitelaar, JK Mick, E Asherson, P Faraone, SV Franke, B Johansson, S Haavik, J Reif, A Bayes, M Cormand, B AF Sanchez-Mora, C. Ribases, M. Ramos-Quiroga, J. A. Casas, M. Bosch, R. Boreatti-Huemmer, A. Heine, M. Jacob, C. P. Lesch, K-P. Fasmer, O. B. Knappskog, P. M. Kooij, J. J. Sandra Kan, C. Buitelaar, J. K. Mick, E. Asherson, P. Faraone, S. V. Franke, B. Johansson, S. Haavik, J. Reif, A. Bayes, M. Cormand, B. TI Meta-Analysis of Brain-Derived Neurotrophic Factor p.Va166Met in Adult ADHD in Four European Populations SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE attention-deficit hyperactivity disorder; adult ADHD; BDNF; case-control association study; meta-analysis ID DEFICIT-HYPERACTIVITY-DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; GENOME-WIDE ASSOCIATION; FAMILY-BASED ASSOCIATION; COMMON VALINE ALLELE; FACTOR BDNF GENE; VAL66MET POLYMORPHISM; BIPOLAR DISORDER; CANDIDATE GENES; MOLECULAR-GENETICS AB Attention-deficit hyperactivity disorder (ADHD) is a multifactorial, neurodevelopmental disorder that often persists into adolescence and adulthood and is characterized by inattention, hyperactivity and impulsiveness. Before the advent of the first genome-wide association studies in ADHD, genetic research had mainly focused on candidate genes related to the dopaminergic and serotoninergic systems, although several other genes had also been assessed. Pharmacological data, analysis of animal models and association studies suggest that Brain-Derived Neurotrophic Factor (BDNF) is also a strong candidate gene for ADHD. Several polymorphisms in BDNF have been reported and studied in psychiatric disorders but the most frequent is the p.Va166Met (rs6265G > A) single nucleotide polymorphism (SNP), with functional effects on the intracellular trafficking and secretion of the protein. To deal with the inconsistency raised among different case-control and family-based association studies regarding the p.Va166Met contribution to ADHD, we performed a meta-analysis of published as well as unpublished data from four different centers that are part of the International Multicentre Persistent ADHD CollaboraTion (IMpACT). A total of 1,445 adulthood ADHD patients and 2,247 sex-matched controls were available for the study. No association between the p.Va166Met polymorphism and ADHD was found in any of the four populations or in the pooled sample. The meta-analysis also showed that the overall gene effect for ADHD was not statistically significant when gender or comorbidity with mood disorders were considered. Despite the potential role of BDNF in ADHD, our data do not support the involvement of p.Va166Met in the pathogenesis of this neuropsychiatric disorder. (C) 2009 Wiley-Liss, Inc. C1 [Sanchez-Mora, C.; Ribases, M.; Ramos-Quiroga, J. A.; Casas, M.; Bosch, R.] Hosp Univ Vall Hebron, Dept Psychiat, Barcelona, Catalonia, Spain. [Sanchez-Mora, C.; Ribases, M.] Hosp Univ Vall Hebron, Psychiat Genet Unit, Barcelona, Catalonia, Spain. [Ramos-Quiroga, J. A.; Casas, M.] Univ Autonoma Barcelona, Dept Psychiat & Legal Med, Catalonia, Spain. [Boreatti-Huemmer, A.; Heine, M.; Jacob, C. P.; Lesch, K-P.; Reif, A.] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany. [Fasmer, O. B.; Haavik, J.] Haukeland Hosp, Div Psychiat, N-5021 Bergen, Norway. [Fasmer, O. B.] Univ Bergen, Dept Clin Med, Sect Psychiat, Bergen, Norway. [Knappskog, P. M.] Haukeland Hosp, Ctr Med Genet & Mol Med, Haukeland, Norway. [Kooij, J. J. Sandra] Program Adult ADHD, Psychomed Programs, PsyQ, The Hague, Netherlands. [Kan, C.; Buitelaar, J. K.; Franke, B.] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands. [Mick, E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mick, E.] Harvard Univ, Sch Med, Boston, MA USA. [Asherson, P.] Inst Psychiat, MRC Social Genet Dev & Psychiat Ctr, London, England. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. [Franke, B.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Johansson, S.; Haavik, J.] Univ Bergen, Dept Biomed, Bergen, Norway. [Bayes, M.] CRG UPF, Genes & Dis Program, Barcelona, Catalonia, Spain. [Bayes, M.] CIBER Epidemiol & Salud Publ, Barcelona, Catalonia, Spain. [Bayes, M.] Ctr Nacl Genotipado, Barcelona, Catalonia, Spain. [Cormand, B.] Univ Barcelona, Fac Biol, Dept Genet, Catalonia, Spain. [Cormand, B.] CIBER Enfermedades Raras, Barcelona, Catalonia, Spain. [Cormand, B.] Univ Barcelona, Inst Biomed, Catalonia, Spain. RP Cormand, B (reprint author), Univ Barcelona, Fac Biol, Dept Genet, Av Diagonal 645,Edifici Annex,3A Planta, E-08028 Barcelona, Spain. EM bcormand@ub.edu RI Franke, Barbara/D-4836-2009; Buitelaar, Jan/E-4584-2012; Johansson, Stefan/C-4394-2011; Cormand, Bru/H-5338-2015; Lesch, Klaus-Peter/J-4906-2013 OI Franke, Barbara/0000-0003-4375-6572; Buitelaar, Jan/0000-0001-8288-7757; Johansson, Stefan/0000-0002-2298-7008; Cormand, Bru/0000-0001-5318-4382; Lesch, Klaus-Peter/0000-0001-8348-153X FU Instituto de Salud Carlos III-FIS, Spain [PI040524, PI041267, PI080519]; Agencia de Gestio d'Ajuts Universitaris i de Recerca-AGAUR [2005SGR00848]; Deutsche Forschungsgemeinschaft [RE1632/1-1, RE1632/1-3, KFO 125, SFB 581, SFB TRR 58]; BMBF [01GV0605, IZKF 01KS9603, N-4]; EC [NEWMOOD LSHM-CT-2003-503474]; Research Council of Norway; Helse Vest; Hersenstichting Nederland (Fonds Psychische Gezondheid) FX Grant sponsor: Instituto de Salud Carlos III-FIS, Spain; Grant Numbers: PI040524, PI041267, PI080519; Grant sponsor: Agencia de Gestio d'Ajuts Universitaris i de Recerca-AGAUR; Grant Number: 2005SGR00848; Grant sponsor: Deutsche Forschungsgemeinschaft; Grant Numbers: RE1632/1-1, RE1632/1-3, KFO 125, SFB 581, SFB TRR 58; Grant sponsor: BMBF; Grant Numbers: 01GV0605, IZKF 01KS9603, N-4; Grant sponsor: EC; Grant Number: NEWMOOD LSHM-CT-2003-503474; Grant sponsor: Research Council of Norway and Helse Vest; Grant sponsor: Hersenstichting Nederland (Fonds Psychische Gezondheid). NR 55 TC 33 Z9 33 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR PY 2010 VL 153B IS 2 BP 512 EP 523 DI 10.1002/ajmg.b.31008 PG 12 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 566NI UT WOS:000275377900017 PM 19603419 ER PT J AU Wang, Y Adamczyk, A Shugart, YY Samuels, JF Grados, MA Greenberg, BD Knowles, JA McCracken, JT Rauch, SL Murphy, DL Rasmussen, SA Cullen, B Pinto, A Fyer, AJ Piacentini, J Pauls, DL Bienvenu, OJ Riddle, M Liang, KY Valle, D Wang, T Nestadt, G AF Wang, Y. Adamczyk, A. Shugart, Y. Y. Samuels, J. F. Grados, M. A. Greenberg, B. D. Knowles, J. A. McCracken, J. T. Rauch, S. L. Murphy, D. L. Rasmussen, S. A. Cullen, B. Pinto, A. Fyer, A. J. Piacentini, J. Pauls, D. L. Bienvenu, O. J. Riddle, M. Liang, K. Y. Valle, D. Wang, T. Nestadt, G. TI A Screen of SLC1A1 for OCD-Related Alleles SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE OCD; SLC1A1; polymorphism ID OBSESSIVE-COMPULSIVE DISORDER; CONFORMATION POLYMORPHISM; TRANSPORTER GENE; ASSOCIATION; AUGMENTATION; LINKAGE AB SLC1A1, which encodes the neuronal and epithelial glutamate transporter, is a promising candidate gene for obsessive-compulsive disorder (OCD). In this study, we conducted capillary electrophoresis single-strand conformation polymorphism (CE-SSCP) screen for all 12 identified exons, including all coding regions and similar to 50 bp of flanking introns of the human SLC1A1 in 378 OCD-affected individuals. Full sequencing was completed on samples that showed an aberrant SSCP tracing for identification of the underlying sequence variants. Our aim was to determine if there are differences in the frequencies of relatively common alleles, or rare functional alleles, in 378 OCD cases and 281 ethnically matched controls. We identified one non-synonymous coding SNP (c.490A > G, T164A) and three synonymous coding SNP (c.81G>C, A27A; c.414A>G, T138T; c.1110T > C, T370T) in case samples. We found no statistical differences in genotype and allele frequencies of common cSNPs in SLC1A1 between the OCD cases and controls. The rare variant T164A was found only in one family. Further investigation of this variant is necessary to determine whether and how it is related to OCD. There was no other evidence of significant accumulation of deleterious coding mutations in SLC1A1 in the OCD cases. (C) 2009 Wiley-Liss, Inc. C1 [Wang, Y.; Samuels, J. F.; Grados, M. A.; Cullen, B.; Bienvenu, O. J.; Riddle, M.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Adamczyk, A.; Valle, D.; Wang, T.] Johns Hopkins Univ, Sch Med, Dept Pediat, Mckusick Nathan Inst Genet Med, Baltimore, MD 21205 USA. [Shugart, Y. Y.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Greenberg, B. D.; Rasmussen, S. A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Knowles, J. A.] Univ So Calif, Dept Psychiat, Los Angeles, CA USA. [McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Rauch, S. L.; Pauls, D. L.] Harvard Univ, Sch Med, Boston, MA USA. [Rauch, S. L.; Pauls, D. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rauch, S. L.; Pauls, D. L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Pinto, A.; Fyer, A. J.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Liang, K. Y.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Wang, Y (reprint author), 1629 Thames St,Suite 401, Baltimore, MD 21231 USA. EM ywang37@jhmi.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Adamczyk, Abby/E-4457-2014; Pinto, Anthony/D-2718-2017; OI Adamczyk, Abby/0000-0001-7653-295X; Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 NR 16 TC 18 Z9 19 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR PY 2010 VL 153B IS 2 BP 675 EP 679 DI 10.1002/ajmg.b.31001 PG 5 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 566NI UT WOS:000275377900036 PM 19569082 ER PT J AU Holland, R Meyers, D Hildebrand, C Bridges, AJ Roach, MA Vogelman, B AF Holland, Robert Meyers, David Hildebrand, Christopher Bridges, Alan J. Roach, Mary A. Vogelman, Bennett TI Creating Champions for Health Care Quality and Safety SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE systems-based learning; quality improvement; patient safety; graduate medical education; health care quality ID IMPROVEMENT; MEDICINE; PERFORMANCE; COMPETENCE; EDUCATION AB Patient safety and quality of care are public concerns that demand personal responsibility at all levels of the health care organization. Senior residents in our graduate medical education program took responsibility for a capstone quality improvement project designed to transform them into champions for health care quality. Residents (n = 26) participated alone or in pairs in a 1-month faculty-mentored rotation at the Veterans Administration Hospital during the 2007-2008 academic year. They completed a Web-based curriculum, identified a quality-of-care issue, applied Plan-Do-Study-Act cycles, authored a report, and engaged colleagues in their innovations during a department-wide presentation. Results indicated that residents demonstrated significantly enhanced knowledge and attitudes about patient safety and quality improvement and provided consistently positive faculty and rotation evaluations. In addition, residents generated 20 quality improvement project proposals with a 50% rate of hospital-wide implementation, leading to meaningful changes in the systems that affect patient care. C1 [Holland, Robert; Meyers, David; Hildebrand, Christopher; Bridges, Alan J.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Roach, Mary A.; Vogelman, Bennett] Univ Wisconsin, Madison Sch Med & Publ Hlth, Madison, WI USA. RP Holland, R (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM Robert.Holland@va.gov FU Medical Education and Research Committee (MERC) of the University of Wisconsin-Madison School of Medicine and Public Health FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: Completion of this article was made possible by a grant from the Medical Education and Research Committee (MERC) of the University of Wisconsin-Madison School of Medicine and Public Health as well as by the support of the Education Innovation Project of the Residency Review Committee for Internal Medicine, of which we are a participating residency. NR 18 TC 12 Z9 12 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAR-APR PY 2010 VL 25 IS 2 BP 102 EP 108 DI 10.1177/1062860609352108 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 566KZ UT WOS:000275370400004 PM 19966115 ER PT J AU Curhan, SG Eavey, R Shargorodsky, J Curhan, GC AF Curhan, Sharon G. Eavey, Roland Shargorodsky, Josef Curhan, Gary C. TI Analgesic Use and the Risk of Hearing Loss in Men SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Analgesics; Hearing loss; Prospective study ID NUTRITION EXAMINATION SURVEY; QUIET-AGED GERBILS; OLDER-ADULTS; COGNITIVE DYSFUNCTION; NATIONAL-HEALTH; INTENSE SOUNDS; UNITED-STATES; OTOTOXICITY; SALICYLATE; ASPIRIN AB BACKGROUND: Hearing loss is a common sensory disorder, yet prospective data oil potentially modifiable risk factors are limited. Regularly used analgesics. the most commonly used drugs in the US, may be ototoxic and contribute to hearing loss. METHODS: We examined the independent association between self-reported professionally diagnosed hearing loss and regular use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen in 26,917 men aged 40-74 years at baseline in 1986. Study participants completed detailed questionnaires at baseline and every 2 years thereafter. Incident cases of new-onset hearing loss were defined as those diagnosed after 1986. Cox proportional hazards multivariate regression was used to adjust for potential confounding factors. RESULTS: During 369,079 person-years of follow-up, 3488 incident cases of hearing loss were reported. Regular use of each analgesic was independently associated with an increased risk of hearing loss. Multivariate-adjusted hazard ratios of hearing loss in regular users (2+ times/week) compared with men Who used the specified analgesic <2 times/week were 1.12 (95% confidence interval [CI], 1.04-1.20) for aspirin, 1.21 (95% CI, 1.11-1.33) for NSAIDs, and 1.22 (95% CI, 1.07-1.39) for acetaminophen. For NSAIDs and acetaminophen, the risk increased with longer duration of regular use. The magnitude of the association was substantially higher in younger men. For men younger than age 50 years, the hazard ratio for hearing loss was 1.33 for regular aspirin use, 1.61 for NSAIDs, and 1.99 for acetaminophen. CONCLUSIONS: Regular use of aspirin, NSAIDs, or acetaminophen increases the risk of hearing loss in men, and the impact is larger on younger individuals. (D 2010 Elsevier Inc. All rights reserved. . The American Journal of Medicine (2010) 123, 231-237 C1 [Curhan, Sharon G.; Shargorodsky, Josef; Curhan, Gary C.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Eavey, Roland] Vanderbilt Univ, Dept Otolaryngol, Nashville, TN USA. [Shargorodsky, Josef] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Curhan, Gary C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Curhan, SG (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM scurhan@partners.org FU National Institutes of Health [P01 CA055075]; Massachusetts Eye and Ear Infirmary Foundation, Boston, Mass FX This work was supported by National Institutes of Health grant P01 CA055075 and the Massachusetts Eye and Ear Infirmary Foundation, Boston, Mass. NR 54 TC 30 Z9 32 U1 4 U2 11 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 MAR PY 2010 VL 123 IS 3 BP 231 EP 237 DI 10.1016/j.amjmed.2009.08.006 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 572EE UT WOS:000275809400012 PM 20193831 ER PT J AU Singh, H Thomas, EJ Sittig, DF Wilson, L Espadas, D Khan, MM Petersen, LA AF Singh, Hardeep Thomas, Eric J. Sittig, Dean F. Wilson, Lindsey Espadas, Donna Khan, Myrna M. Petersen, Laura A. TI Notification of Abnormal Lab Test Results in an Electronic Medical Record: Do Any Safety Concerns Remain? SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Abnormal diagnostic test results; Communication; Diagnostic errors; Electronic medical records; Health information technology; Patient follow-up; Patient safety; Primary care ID INFORMATION-TECHNOLOGY; FOLLOW-UP; COMMUNICATION; ERRORS; DIAGNOSIS AB BACKGROUND: Follow-up of abnormal outpatient laboratory test results is a major patient safety concern. Electronic medical records can potentially address this concern through automated notification. We examined whether automated notifications of abnormal laboratory results (alerts) in an integrated electronic medical record resulted in timely follow-up actions. METHODS: We studied 4 alerts: hemoglobin Alc >= 15%, positive hepatitis C antibody, prostate-specific antigen >= 15 ng/mL and thyroid-stimulating hormone >= 15 mlU/L. An alert tracking system determined whether the alert was acknowledged (ie, provider clicked on and opened the message) within 2 weeks of transmission;. acknowledged alerts were considered read. Within 30 days of result transmission, record review and provider contact determined follow-up actions (eg. patient contact, treatment). Multivariable logistic regression models analyzed predictors for lack of timely follow-up. RESULTS: Between May and December 2008, 78,158 tests (hemoglobin Ale, hepatitis C antibody, thyroid- stimulating hormone, and prostate-specific antigen) were performed, of which 1163 (1.48%) were transmitted as alerts; 10.2% of these (119/1163) were unacknowledged. Timely follow-up was lacking in 79 (6.8%), and was statistically not different for acknowledged and unacknowledged alerts (6.4% vs 10.1 %; P = .13). Of 1163 alerts, 202 (17.4%) arose from unnecessarily ordered (redundant) tests. Alerts for a new versus known diagnosis were more likely to lack timely follow-up (odds ratio 7.35; 95% confidence interval, 4.16-12.97), whereas alerts related to redundant tests were less likely to lack timely follow-up (odds ratio 0.24; 95% confidence interval, 0.07-0.84). CONCLUSIONS: Safety concerns related to timely patient follow-up remain despite automated notification of non-life-threatening abnormal laboratory results in the outpatient setting, Published by, Elsevier Inc. . The American Journal of Medicine (2010) 123, 238-244 C1 [Singh, Hardeep; Wilson, Lindsey; Espadas, Donna; Khan, Myrna M.; Petersen, Laura A.] Baylor Coll Med, Houston VA Hlth Serv Res & Dev Ctr Excellence, Ctr Inquiry Improve Outpatient Safety Effect Elec, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep; Wilson, Lindsey; Espadas, Donna; Khan, Myrna M.; Petersen, Laura A.] Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. [Thomas, Eric J.] Univ Texas Houston, Div Gen Med, Dept Med,Univ Texas Med Sch Houston, Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. [Sittig, Dean F.] Univ Texas Sch Hlth Informat Sci, Houston, TX USA. [Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.tmc.edu FU NIH [K23CA125585]; VA National Center of Patient Safety; Agency for Health Care Research and Quality Health Services Research Demonstration and Dissemination [R18 HS17244-02]; Houston VA Health Set-vices Research & Development Center of Excellence [HFP90-020] FX The study was supported by an NIH K23 career development award (K23CA125585) to Dr. Singh, the VA National Center of Patient Safety, Agency for Health Care Research and Quality Health Services Research Demonstration and Dissemination Grant (R18 HS17244-02) to Dr. Thomas, and in part by the Houston VA Health Set-vices Research & Development Center of Excellence (HFP90-020). These sources had no role in the design and conduct of the study: collection, management. analysis. and interpretation of the data: and preparation, review, or approval of the manuscript. NR 26 TC 53 Z9 53 U1 4 U2 7 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 MAR PY 2010 VL 123 IS 3 BP 238 EP 244 DI 10.1016/j.amjmed.2009.07.027 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 572EE UT WOS:000275809400013 PM 20193832 ER PT J AU Choi, AI Hernandez, GT Rodriguez, RA O'Hare, AM AF Choi, Andy I. Hernandez, German T. Rodriguez, Rudolph A. O'Hare, Ann M. TI Influence of Hispanic Ethnicity and Diabetic End-stage Renal Disease Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Choi, Andy I.] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Hernandez, German T.] Texas Tech Univ, Hlth Sci Ctr, Dept Med, Paul L Foster Sch Med, El Paso, TX USA. [Rodriguez, Rudolph A.; O'Hare, Ann M.] Univ Washington, Dept Med, VA Puget Sound Healthcare Syst, Seattle, WA USA. RP Choi, AI (reprint author), Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA 94143 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 MAR PY 2010 VL 123 IS 3 BP E21 EP E21 DI 10.1016/j.amjmed.2009.11.002 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 572EE UT WOS:000275809400031 ER PT J AU Little, SE Janakiraman, V Kaimal, A Musci, T Ecker, J Caughey, AB AF Little, Sarah E. Janakiraman, Vanitha Kaimal, Anjali Musci, Thomas Ecker, Jeffrey Caughey, Aaron B. TI The cost-effectiveness of prenatal screening for spinal muscular atrophy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med DE cost-effectiveness; decision analysis; prenatal screening; spinal muscular atrophy ID ECONOMIC-EVALUATION; PREGNANT-WOMEN; AMNIOCENTESIS; DIAGNOSIS; CARE AB OBJECTIVE: We sought to investigate the cost-effectiveness of prenatal screening for spinal muscular atrophy (SMA). STUDY DESIGN: A decision analytic model was created to compare a policy of universal SMA screening to that of no screening. The primary outcome was incremental cost per maternal quality-adjusted life year. Probabilities, costs, and outcomes were estimated through literature review. Univariate and multivariate sensitivity analyses were performed to test the robustness of our model to changes in baseline assumptions. RESULTS: Universal screening for SMA is not cost-effective at $4.9 million per quality-adjusted life year. In all, 12,500 women need to be screened to prevent 1 case of SMA, at a cost of $5.0 million per case averted. Our results were most sensitive to the baseline prevalence of disease. CONCLUSION: Universal prenatal screening for SMA is not cost-effective. For populations at high risk, such as those with a family history, SMA testing may be a cost-effective strategy. C1 [Little, Sarah E.; Janakiraman, Vanitha; Kaimal, Anjali; Ecker, Jeffrey] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Musci, Thomas] San Francisco Perinatal Associates, San Francisco, CA USA. [Caughey, Aaron B.] Univ Calif San Francisco, Sch Med, Decis & Econ Analyses Reprod & Womens Hlth Grp, San Francisco, CA USA. [Caughey, Aaron B.] Univ Calif San Francisco, Sch Med, Ctr Clin & Policy Perinatal Res, San Francisco, CA USA. RP Little, SE (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 25 TC 5 Z9 6 U1 1 U2 4 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 MAR PY 2010 VL 202 IS 3 AR 253.e1 DI 10.1016/j.ajog.2010.01.032 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 568IV UT WOS:000275516900015 PM 20207244 ER PT J AU Steinberg, G Lee, C Rauh-Hain, JA Ecker, J Khankin, EV Hsu, CD Cohen, B Rana, S Karumanchi, SA Thadhani, R Hacker, MR Lim, KH AF Steinberg, Guy Lee, Chulmin Rauh-Hain, Jose Alejandro Ecker, Jeffrey Khankin, Eliyahu V. Hsu, Chaur-Dong Cohen, Bruce Rana, Sarosh Karumanchi, S. Ananth Thadhani, Ravi Hacker, Michele R. Lim, Kee-Hak TI Early-pregnancy soluble Fas levels in idiopathic small-for-gestational-age pregnancies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE apoptosis; sFas ID PLACENTAL GROWTH-FACTOR; MEDIATED APOPTOSIS; PREECLAMPSIA; SERUM; RISK; CYTOTROPHOBLASTS; RESTRICTION; SURVIVAL; CELLS AB OBJECTIVE: We sought to determine first-and second-trimester serum soluble Fas (sFas) and placental growth factor (PlGF) levels in idiopathic small-for-gestational-age (SGA) pregnancies. STUDY DESIGN: We measured sFas and PlGF levels in women who delivered SGA infants uncomplicated by preeclampsia and in control subjects. For sFas there were 34 cases and 318 control subjects in the first trimester and 9 cases and 11 control subjects in the second trimester. For PlGF there were 31 cases and 281 control subjects in the first trimester and 8 cases and 11 control subjects in the second trimester. RESULTS: SGA pregnancies had lower sFas levels than control subjects in the second trimester (3703 +/- 209 pg/mL vs 4562 +/- 241 pg/mL; P=.015), but not in the first trimester (4892 +/- 191 pg/mL vs 4971 +/- 177 pg/mL; P=.68). There was no difference in PlGF levels between SGA and normal pregnancies in both trimesters. CONCLUSION: Serum sFas levels were lower in idiopathic SGA pregnancies in the second trimester, but not in the first. There was no difference in serum PlGF levels in either trimester. C1 [Steinberg, Guy; Lee, Chulmin; Rauh-Hain, Jose Alejandro; Ecker, Jeffrey; Cohen, Bruce; Rana, Sarosh; Karumanchi, S. Ananth; Thadhani, Ravi; Hacker, Michele R.; Lim, Kee-Hak] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA USA. [Karumanchi, S. Ananth; Thadhani, Ravi] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rauh-Hain, Jose Alejandro; Ecker, Jeffrey; Thadhani, Ravi] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA. [Hsu, Chaur-Dong] Nassau Univ, Med Ctr, Dept Obstet & Gynecol, E Meadow, NY USA. [Lee, Chulmin] Inje Univ, Sanggye Paik Hosp, Dept Obstet & Gynecol, Seoul, South Korea. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Steinberg, G (reprint author), 330 Brookline Ave,Kirstein 338, Boston, MA 02215 USA. EM guysteinberg@hotmail.com RI Khankin, Eli/M-7648-2013; OI Hacker, Michele/0000-0003-0217-9991; Lee, Chulmin/0000-0003-2510-4271 FU Beth Israel Deaconess Medical Center FX Supported by the Beth Israel Deaconess Medical Center. NR 26 TC 0 Z9 0 U1 0 U2 2 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 MAR PY 2010 VL 202 IS 3 AR 299.e1 DI 10.1016/j.ajog.2009.12.017 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 568IV UT WOS:000275516900033 PM 20207247 ER PT J AU Jakobiec, FA Lam, H Bhat, P Pineda, R AF Jakobiec, Frederick A. Lam, Helene Bhat, Pooja Pineda, Roberto TI Non-Syndromic Supernumerary Caruncles Causing Ocular Irritation After Cataract Surgery: A Critical Review of Caruncular Dysgeneses SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Review ID LESIONS AB PURPOSE: To describe a patient with 2 ipsilateral supernumerary caruncles and to determine if they are predictive of associated abnormalities. DESIGN: Retrospective and interventional clinicopathologic study with a critical review of the literature over the past 100 years. METHODS: Assessment of clinical features and histopathologic findings in paraffin-embedded tissue sections stained with hematoxylin and eosin, Masson trichrome, periodic acid-Schiff (PAS) reaction with and without diastase, and Ziehl-Neelsen method. RESULTS: Two placoid lesions causing ocular irritation after routine phacoemulsification were discovered in the inferomedial palpebral conjunctiva. They were totally separate from a normal caruncle. Their surface was studded with yellowish micronodules with projecting white vellus hairs. There were no associated local ophthalmic or systemic abnormalities. Microscopically, they were covered by a goblet cell-rich, nonkeratinizing squamous epithelium with subadjacent pilosebaceous units, the hairs of which were highlighted by the Masson trichrome and Ziehl-Neelsen stains, and small lobules of lacrimal gland tissue. The ocular irritation has not returned after surgery. CONCLUSIONS: A literature review confirms that supernumerary (extra) caruncles coexisting with a normal caruncle are always unilateral and unassociated with any other ocular anomalies, as in the current case. They may, however, cause ocular irritation. They must be distinguished from ectopic (topographically displaced) or dysplastic caruncles that are generally bilateral and often associated with ocular adnexal abnormalities or Golden, har syndrome. Ectopic or dysplastic caruncles, but not supernumerary ones, are characteristically accompanied by plical abnormalities or its absence. Well-documented supernumerary and ectopic caruncles have always been located in the inferior palpebral conjunctiva. (Am J Ophthalmol 2010;149:398-404. (C) 2010 by Elsevier Inc. All rights reserved.) C1 [Jakobiec, Frederick A.; Lam, Helene; Bhat, Pooja; Pineda, Roberto] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Lam, Helene; Bhat, Pooja; Pineda, Roberto] Harvard Univ, Sch Med, Boston, MA USA. [Jakobiec, Frederick A.; Bhat, Pooja] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Pineda, Roberto] Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Suite 321,3rd Fl,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 34 TC 5 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2010 VL 149 IS 3 BP 398 EP 404 DI 10.1016/j.ajo.2009.09.028 PG 7 WC Ophthalmology SC Ophthalmology GA 565MD UT WOS:000275296400008 PM 20172067 ER PT J AU Daniel, E Thorne, JE Newcomb, CW Pujari, SS Kacmaz, RO Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Suhler, EB Foster, CS Jabs, DA Kempen, JH AF Daniel, Ebenezer Thorne, Jennifer E. Newcomb, Craig W. Pujari, Siddharth S. Kacmaz, R. Oktay Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Foster, C. Stephen Jabs, Douglas A. Kempen, John H. TI Mycophenolate Mofetil for Ocular Inflammation SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EYE DISEASE; IMMUNOSUPPRESSIVE THERAPY; UVEITIS; AGENT; DRUGS AB PURPOSE: To evaluate mycophenolate mofetil as a single noncorticosteroid immunosuppressive treatment for noninfectious ocular inflammatory diseases. DESIGN: Retrospective cohort study. METHODS: Characteristics of patients with noninfectious ocular inflammation treated with mycophenolate mofetil at 4 subspecialty clinics from 1995 to 2007 were abstracted by expert reviewers in a standardized chart review of every eye at every visit. Main outcomes measured were control of inflammation, corticosteroid-sparing effects, and discontinuation of mycophenolate mofetil (including the reasons for discontinuation). Survival analysis was used to estimate the incidence of outcomes, and to identify risk factors for each. RESULTS: Among 236 patients (397 eyes) treated with mycophenolate mofetil monotherapy, 20.3%, 11.9%, and 39.8% had anterior uveitis, intermediate uveitis, and posterior uveitis or panuveitis respectively; 14% had scleritis; 7.6% had mucous membrane pemphigoid; and 6.4% had other ocular inflammatory diseases. By Kaplan-Meier estimation, complete control of inflammation-sustained over consecutive visits spanning at least 28 days-was achieved in 53% and 73% of patients within 6 months and 1 year respectively. Systemic corticosteroid dosage was reduced to 10 mg of prednisone or less, while maintaining sustained control of inflammation, in 41% and 55% of patients in 6 months and 1 year respectively. Twelve percent of patients discontinued mycophenolate mofetil within the first year because of side effects of therapy. CONCLUSIONS: Given sufficient time, mycophenolate mofetil was effective in managing ocular inflammation in approximately half of the treated patients. Treatment, limiting side effects were observed in 12% of patients and typically were reversible. (Am J Ophthalmol 2010;149: 423-432. (C) 2010 by Elsevier Inc. All rights reserved.) C1 [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Sch Med, Philadelphia, PA 19104 USA. [Daniel, Ebenezer] Univ Penn, Sch Med, Fundus Photograph Reading Ctr, Philadelphia, PA 19104 USA. [Newcomb, Craig W.; Jabs, Douglas A.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Newcomb, Craig W.; Kempen, John H.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Thorne, Jennifer E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Pujari, Siddharth S.; Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Dept Ophthalmol, Tarpon Springs, FL USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Kacmaz, R. Oktay; Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Sch Med, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU NEI NIH HHS [R01 EY014943-05, EY014943, R56 EY014943, R01 EY014943] NR 27 TC 77 Z9 81 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2010 VL 149 IS 3 BP 423 EP 432 DI 10.1016/j.ajo.2009.09.026 PG 10 WC Ophthalmology SC Ophthalmology GA 565MD UT WOS:000275296400011 PM 20042178 ER PT J AU Baker, AM Klein, RL Haeri, S Moss, KL Boggess, KA AF Baker, Arthur M. Klein, Richard L. Haeri, Sina Moss, Kevin L. Boggess, Kim A. TI Association of Midgestational Paraoxonase 1 Activity with Pregnancies Complicated by Preeclampsia SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE Lipid dysfunction; oxidative stress; paraoxonase; preeclampsia ID DEPENDENT DIABETES-MELLITUS; SERUM PARAOXONASE; ANTIOXIDANT; WOMEN; ARYLESTERASE; COHORT; RISK AB The antioxidant enzyme paraoxonase 1 is a marker of oxidative stress and has been implicated in the pathogenesis of preeclampsia. Our objective was to determine if an association exists between low paraoxonase 1 activity at midgestation and the development of preeclampsia. We conducted a case-control study of 50 women with preeclampsia and 101 women with uncomplicated term deliveries. Maternal serum collected at 15 to 20 weeks was used to measure paraoxonase 1 activity using two substrates: paraoxon and phenylacetate (arylesterase activity). The groups did not differ with respect to maternal demographics. Paraoxonase 1 activity (paraoxon) was significantly higher in women with preeclampsia compared with controls (19.4 +/- 9.4 versus 15.6 +/- 8.0 change in absorbance per minute (dA/min), p = 0.009). When stratified by disease severity, paraoxonase 1 activity (paraoxon) was highest in women with severe preeclampsia (21.6 +/- 9.1 versus 15.6 +/- 8.0 dA/min, p = 0.002). We observed a trend toward higher arylesterase activity in women with preeclampsia compared with controls (0.343 +/- 0.07 versus 0.323 +/- 0.06 dA/min, p = 0.06). Midgestational paraoxonase 1 activity is higher in women with preeclampsia before clinical signs of the disease are present. Prospective studies are needed to determine the significance of paraoxonase 1 in the pathogenesis of preeclampsia. C1 [Baker, Arthur M.; Haeri, Sina; Boggess, Kim A.] Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chapel Hill, NC 27599 USA. [Klein, Richard L.] Med Univ S Carolina, Dept Med, Div Endocrinol Metab & Med Genet, Charleston, SC 29425 USA. [Klein, Richard L.] Ralph H Johnson Dept Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. [Moss, Kevin L.] Univ N Carolina, Dept Dent, Chapel Hill, NC 27599 USA. RP Baker, AM (reprint author), Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, 3010 Old Clin Bldg,CB 7516, Chapel Hill, NC 27599 USA. EM abaker2@med.unc.edu FU University of North Carolina; Department of Veterans' Affairs FX This work was supported by a grant from The University of North Carolina Medical Alumni Endowment Fund (A. M. B.) and funding from a Department of Veterans' Affairs MERIT award (R. L. K.). The authors gratefully acknowledge the technical assistance of Ms. Andrea Semler. NR 25 TC 5 Z9 7 U1 0 U2 0 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 MAR PY 2010 VL 27 IS 3 BP 205 EP 210 DI 10.1055/s-0029-1236438 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 557JI UT WOS:000274665000004 PM 19685420 ER PT J AU Atkinson, GJ Lee, MY Mehta, MK AF Atkinson, George J. Lee, Michael Y. Mehta, Madhu K. TI Heterotopic Ossification in the Residual Lower Limb in an Adult Nontraumatic Amputee Patient SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Amputation; Ossification; Heterotopic; Adult; Rehabilitation ID BONE; OVERGROWTH; AMPUTATION AB Atkinson GJ, Lee MY, Mehta MK: Heterotopic ossification in the residual lower limb in an adult nontraumatic amputee patient. Am J Phys Med Rehabil 2010;89:245-248. Heterotopic ossification usually occurs in association with various neurologic injuries, trauma, and burns. There have been few reports in the literature of heterotopic bone formation at the distal residual limb in the adult amputee population. All previous cases with a documented cause have involved traumatic amputations. An adult diabetic patient who underwent left below-the-knee amputation for progressive Charcot foot is presented. The patient began to experience residual limb pain and decline in functional mobility 4-5 mos after surgery. Radiographs demonstrated heterotopic bone around the distal tibial and fibular remnant with extension into adjacent soft tissue. Triple-phase bone scan testing and tissue biopsy verified active heterotopic ossification. The patient was treated with etidronate and eventually was able to ambulate with a prosthesis on a regular basis. This case demonstrates that heterotopic ossification may occur and be a source of residual limb pain in the adult nontraumatic amputee population. C1 [Atkinson, George J.; Lee, Michael Y.; Mehta, Madhu K.] Univ N Carolina, Sch Med, Dept Phys Med & Rehabil, Chapel Hill, NC USA. RP Atkinson, GJ (reprint author), S Texas Vet Hlth Care Syst, Dept Phys Med & Rehabil, 1629 Treasure Hills Blvd,Suite B-5, Harlingen, TX 78550 USA. NR 12 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAR PY 2010 VL 89 IS 3 BP 245 EP 248 DI 10.1097/PHM.0b013e3181c5657c PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 569WM UT WOS:000275633500009 PM 19966560 ER PT J AU Liu, JR Wu, XX Franklin, JL Messina, JL Hill, HS Moellering, DR Walton, RG Martin, M Garvey, WT AF Liu, Jiarong Wu, Xuxia Franklin, John L. Messina, Joseph L. Hill, Helliner S. Moellering, Douglas R. Walton, R. Grace Martin, Mitchell Garvey, W. Timothy TI Mammalian Tribbles homolog 3 impairs insulin action in skeletal muscle: role in glucose-induced insulin resistance SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glucose toxicity; type 2 diabetes; insulin signaling ID FUNCTIONAL Q84R POLYMORPHISM; ACTIVATED PROTEIN-KINASE; METABOLIC SYNDROME; CELL-DEATH; GLUT4 TRANSLOCATION; SIGNAL-TRANSDUCTION; 3T3-L1 ADIPOCYTES; TRANSPORT SYSTEM; LIPID-METABOLISM; TRB3 EXPRESSION AB Liu J, Wu X, Franklin JL, Messina JL, Hill HS, Moellering DR, Walton RG, Martin M, Garvey WT. Mammalian Tribbles homolog 3 impairs insulin action in skeletal muscle: role in glucose-induced insulin resistance. Am J Physiol Endocrinol Metab 298: E565-E576, 2010. First published December 8, 2009; doi:10.1152/ajpendo. 00467.2009.-Tribbles homolog 3 (TRIB3) was found to inhibit insulin-stimulated Akt phosphorylation and modulate gluconeogenesis in rodent liver. Currently, we examined a role for TRIB3 in skeletal muscle insulin resistance. Ten insulin-sensitive, ten insulin-resistant, and ten untreated type 2 diabetic (T2DM) patients were metabolically characterized by hyperinsulinemic euglycemic glucose clamps, and biopsies of vastus lateralis were obtained. Skeletal muscle samples were also collected from rodent models including streptozotocin (STZ)-induced diabetic rats, db/db mice, and Zucker fatty rats. Finally, L6 muscle cells were used to examine regulation of TRIB3 by glucose, and stable cell lines hyperexpressing TRIB3 were generated to identify mechanisms underlying TRIB3-induced insulin resistance. We found that 1) skeletal muscle TRIB3 protein levels are significantly elevated in T2DM patients; 2) muscle TRIB3 protein content is inversely correlated with glucose disposal rates and positively correlated with fasting glucose; 3) skeletal muscle TRIB3 protein levels are increased in STZ-diabetic rats, db/db mice, and Zucker fatty rats; 4) stable TRIB3 hyperexpression in muscle cells blocks insulin-stimulated glucose transport and glucose transporter 4 (GLUT4) translocation and impairs phosphorylation of Akt, ERK, and insulin receptor substrate-1 in insulin signal transduction; and 5) TRIB3 mRNA and protein levels are increased by high glucose concentrations, as well as by glucose deprivation in muscle cells. These data identify TRIB3 induction as a novel molecular mechanism in human insulin resistance and diabetes. TRIB3 acts as a nutrient sensor and could mediate the component of insulin resistance attributable to hyperglycemia (i.e., glucose toxicity) in diabetes. C1 [Wu, Xuxia; Hill, Helliner S.; Moellering, Douglas R.; Walton, R. Grace; Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Messina, Joseph L.; Garvey, W. Timothy] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Liu, Jiarong; Franklin, John L.; Messina, Joseph L.] Univ Alabama Birmingham, Dept Pathol, Div Mol & Cellular Pathol, Birmingham, AL 35294 USA. [Martin, Mitchell] Hoffmann La Roche Inc, Dept Res Informat Genet & Gen, Preclin Res & Dev, Nutley, NJ 07110 USA. RP Wu, XX (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, 1675 Univ Blvd, Birmingham, AL 35294 USA. EM xuxiawu@uab.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-038764, DK-083562, DK-62071]; National Heart, Lung, and Blood Institute [HL-055782]; American Heart Association; Department of Defense [W81XWH-0510387]; Merit Review Program of the Department of Veterans Affairs; University of Alabama at Birmingham (UAB) Center for Clinical and Translational Science [UL1 RR025777]; UAB Clinical Nutrition Research Unit [P30-DK56336]; UAB Diabetes Research and Training Center [P60-DK079626] FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-038764, DK-083562, and DK-62071 and National Heart, Lung, and Blood Institute Grant HL-055782, American Heart Association Beginning Grant-in-Aid (to X. Wu), the Department of Defense (W81XWH-0510387), and the Merit Review Program of the Department of Veterans Affairs (to W. T. Garvey and J. L. Messina). We also gratefully acknowledge the support of the University of Alabama at Birmingham (UAB) Center for Clinical and Translational Science (UL1 RR025777), the UAB Clinical Nutrition Research Unit (P30-DK56336), and the UAB Diabetes Research and Training Center (P60-DK079626). NR 66 TC 32 Z9 35 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAR PY 2010 VL 298 IS 3 BP E565 EP E576 DI 10.1152/ajpendo.00467.2009 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 557YA UT WOS:000274705200020 PM 19996382 ER PT J AU Bachiller, PR Nakanishi, H Roberts, JD AF Bachiller, Patricia R. Nakanishi, Hidehiko Roberts, Jesse D., Jr. TI Transforming growth factor-beta modulates the expression of nitric oxide signaling enzymes in the injured developing lung and in vascular smooth muscle cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE soluble guanylate cyclase; cGMP-dependent protein kinase I; bronchopulmonary dysplasia; hyperoxia ID DEPENDENT PROTEIN-KINASE; SOLUBLE GUANYLATE-CYCLASE; NEWBORN MOUSE LUNG; PULMONARY-HYPERTENSION; TGF-BETA; RAT LUNG; BRONCHOPULMONARY-DYSPLASIA; ENDOTHELIAL-CELLS; MESSENGER-RNA; FETAL LAMBS AB Bachiller PR, Nakanishi H, Roberts JD Jr. Transforming growth factor-beta modulates the expression of nitric oxide signaling enzymes in the injured developing lung and in vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 298: L324-L334, 2010. First published December 18, 2009; doi:10.1152/ajplung.00181.2009.-Nitric oxide signaling has an important role in regulating pulmonary development and function. Expression of soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase I (PKGI), both critical mediators of nitric oxide (NO) signaling, is diminished in the injured newborn lung through unknown mechanisms. Recent studies suggest that excessive transforming growth factor-beta (TGF-beta) activity inhibits injured newborn lung development. To explore mechanisms that regulate pulmonary NO signaling, we tested whether TGF-beta decreases sGC and PKGI expression in the injured developing lung and pulmonary vascular smooth muscle cells (SMC). We found that chronic oxygen-induced lung injury decreased pulmonary sGC alpha(1) and PKGI immunoreactivity in mouse pups and that exposure to a TGF-beta -neutralizing antibody prevented this reduction of sGC and PKGI protein expression. In addition, TGF-beta(1) decreased expression of NO signaling enzymes in freshly isolated pulmonary microvascular SMC/myofibroblasts, suggesting that TGF-beta has a direct role in modulating NO signaling in the pup lung. Moreover, TGF-beta(1) decreased sGC and PKGI expression in pulmonary artery and aortic SMC from adult rats and mice, suggesting a general role for TGF-beta in modulating NO signaling in vascular SMC. Although other cytokines decrease sGC mRNA stability, TGF-beta did not modulate sGC alpha(1) or PKGI beta mRNA turnover in vascular SMC. These studies indicate for the first time that TGF-beta decreases NO signaling enzyme expression in the injured developing lung and pulmonary vascular SMC. Moreover, they suggest that TGF-beta-neutralizing molecules might counteract the effects of injury on NO signaling in the newborn lung. C1 [Bachiller, Patricia R.; Nakanishi, Hidehiko; Roberts, Jesse D., Jr.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Bachiller, Patricia R.; Nakanishi, Hidehiko; Roberts, Jesse D., Jr.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Roberts, Jesse D., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Roberts, Jesse D., Jr.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Roberts, Jesse D., Jr.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Roberts, JD (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM roberts@cvrc.mgh.harvard.edu FU National Institutes of Health [5-T32-GM-07592, 1-R01-HL-080316]; INO Therapeutics/Ikaria FX This work was supported by National Institutes of Health Grants 5-T32-GM-07592 (to P. R. Bachiller) and 1-R01-HL-080316 (to J. D. Roberts, Jr.) and INO Therapeutics/Ikaria. NR 86 TC 11 Z9 13 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAR PY 2010 VL 298 IS 3 BP L324 EP L334 DI 10.1152/ajplung.00181.2009 PG 11 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 559VX UT WOS:000274857200007 PM 20023176 ER PT J AU Paunescu, TG Ljubojevic, M Russo, LM Winter, C McLaughlin, MM Wagner, CA Breton, S Brown, D AF Paunescu, Teodor G. Ljubojevic, Marija Russo, Leileata M. Winter, Christian McLaughlin, Margaret M. Wagner, Carsten A. Breton, Sylvie Brown, Dennis TI cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE proton pump; H(+)-ATPase; immunocytochemistry; membrane trafficking; acid-base sensing; phosphorylation ID VACUOLAR H+-ATPASE; SOLUBLE ADENYLYL-CYCLASE; EPIDIDYMAL CLEAR CELLS; B2 SUBUNIT ISOFORM; PROTEIN-KINASE-A; RAT-KIDNEY; EPITHELIAL-CELLS; SECRETING CELLS; BINDING PROTEIN; ACID AB Paunescu TG, Ljubojevic M, Russo LM, Winter C, McLaughlin MM, Wagner CA, Breton S, Brown D. cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells. Am J Physiol Renal Physiol 298: F643-F654, 2010. First published January 6, 2010; doi:10.1152/ajprenal.00584.2009.-Kidney proton-secreting A-intercalated cells (A-IC) respond to systemic acidosis by accumulating the vacuolar ATPase (V-ATPase) in their apical membrane and by increasing the length and number of apical microvilli. We show here that the cell-permeant cAMP analog CPT-cAMP, infused in vivo, results in an almost twofold increase in apical V-ATPase accumulation in AE1-positive A-IC within 15 min and that these cells develop an extensive array of apical microvilli compared with controls. In contrast, no significant change in V-ATPase distribution could be detected by immunocytochemistry in B-intercalated cells at the acute time point examined. To show a direct effect of cAMP on A-IC, we prepared cell suspensions from the medulla of transgenic mice expressing EGFP in IC (driven by the B1-subunit promoter of the V-ATPase) and exposed them to cAMP analogs in vitro. Three-dimensional reconstructions of confocal images revealed that cAMP induced a time-dependent growth of apical microvilli, starting within minutes after addition. This effect was blocked by the PKA inhibitor myristoylated PKI. These morphological changes were paralleled by increased cAMP-mediated proton extrusion (pH(i) recovery) by A-IC in outer medullary collecting ducts measured using the ratiometric probe BCECF. These results, and our prior data showing that the bicarbonate-stimulated soluble adenylyl cyclase (sAC) is highly expressed in kidney intercalated cells, support the idea that cAMP generated either by sAC, or by activation of other signaling pathways, is part of the signal transduction mechanism involved in acid-base sensing and V-ATPase membrane trafficking in kidney intercalated cells. C1 [Paunescu, Teodor G.; Ljubojevic, Marija; Russo, Leileata M.; McLaughlin, Margaret M.; Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, MGH Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Ljubojevic, Marija; Russo, Leileata M.; McLaughlin, Margaret M.; Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Ljubojevic, Marija; Russo, Leileata M.; McLaughlin, Margaret M.; Breton, Sylvie; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Winter, Christian; Wagner, Carsten A.] Univ Zurich, Inst Physiol, Zurich, Switzerland. [Winter, Christian; Wagner, Carsten A.] Zurich Ctr Integrat Human Physiol, Zurich, Switzerland. RP Brown, D (reprint author), Massachusetts Gen Hosp, MGH Ctr Syst Biol, Program Membrane Biol, Simches Res Bldg,185 Cambridge St,CPZN 8020, Boston, MA 02114 USA. EM brown.dennis@mgh.harvard.edu FU National Institutes of Health [DK-73266, DK-42956, DK-38452, HD-40793]; Swiss National Science Foundation [3100A0-122217]; Juvenile Diabetes Research Foundation International; Boston Area Diabetes and Endocrinology Research Center [DK-57521]; Center for the Study of Inflammatory Bowel Disease [DK-43341] FX This work was supported by National Institutes of Health grants DK-73266 (to T. G. Pa. unescu), DK-42956 (to D. Brown), DK-38452 (to S. Breton and D. Brown), and HD-40793 (to S. Breton). C. A. Wagner was supported by the Swiss National Science Foundation (3100A0-122217). L. M. Russo is the recipient of an Advanced Postdoctoral Award from the Juvenile Diabetes Research Foundation International. The Microscopy Core Facility of the Program in Membrane Biology received additional support from the Boston Area Diabetes and Endocrinology Research Center (DK-57521) and from the Center for the Study of Inflammatory Bowel Disease (DK-43341). NR 70 TC 68 Z9 68 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2010 VL 298 IS 3 BP F643 EP F654 DI 10.1152/ajprenal.00584.2009 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 572TM UT WOS:000275856000018 PM 20053793 ER PT J AU Woods, SS Jaen, CR AF Woods, Susan Swartz Jaen, Carlos Roberto TI Increasing Consumer Demand for Tobacco Treatments Ten Design Recommendations for Clinicians and Healthcare Systems SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SMOKING-CESSATION TREATMENTS; DEPENDENCE TREATMENT; PUBLIC-HEALTH; UNITED-STATES; PATIENT; SATISFACTION; SMOKERS; PHYSICIANS; BEHAVIORS; SERVICES AB Health professionals play an important role in addressing patient tobacco use in clinical settings. While there is clear evidence that identifying tobacco use and assisting smokers in quitting affects outcomes, challenges to improve routine, clinician-delivered tobacco intervention persist. The Consumer Demand Initiative has identified simple design principles to increase consumers' use of proven tobacco treatments. Applying these design strategies to activities across the healthcare system, we articulate ten recommendations that can be implemented in the context of most clinical systems where most clinicians work. The recommendations are: (1) reframe the definition of success, (2) portray proven treatments as the best care, (3) redesign the 5A's of tobacco intervention, (4) be ready to deliver the right treatment at the right time, (5) move tobacco from the social history to the problem list, (6) use words as therapy and language that makes sense, (7) fit tobacco treatment into clinical team workflows, (8) embed tobacco treatment into health information technology, (9) make every encounter an opportunity to intervene, and (10) end social disparities for tobacco users. Clinical systems need to change to improve tobacco treatment implementation. The consumer- and clinician-centered recommendations provide a roadmap that focuses on increasing clinician performance through greater understanding of the clinician's role in helping tobacco users, highlighting the value of evidence-based tobacco treatments, employing shared decision-making skills, and integrating routine tobacco treatment into clinical system routines. (Am J Prev Med 2010;38(3S):S385-S392) Published by Elsevier Inc. on behalf of American journal of Preventive Medicine C1 [Woods, Susan Swartz] Portland VA Med Ctr, Portland, OR 97239 USA. [Woods, Susan Swartz] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Jaen, Carlos Roberto] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Woods, SS (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM woodssus@ohsu.edu NR 50 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 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAR PY 2010 VL 38 IS 3 SU 3 BP S385 EP S392 DI 10.1016/j.amepre.2009.12.003 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 566OX UT WOS:000275383200013 PM 20176312 ER PT J AU Freeman, MP AF Freeman, Marlene P. TI Nutrition and Psychiatry SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID DIETARY PATTERNS; MENTAL-HEALTH; DEPRESSION; DISORDERS; DISEASE; WOMEN C1 Massachusetts Gen Hosp, Newton, MA 02461 USA. RP Freeman, MP (reprint author), Massachusetts Gen Hosp, 1226 99 Needham St, Newton, MA 02461 USA. EM mfreeman@partners.org NR 11 TC 11 Z9 11 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2010 VL 167 IS 3 BP 244 EP 247 DI 10.1176/appi.ajp.2009.09121746 PG 4 WC Psychiatry SC Psychiatry GA 562MR UT WOS:000275056300003 PM 20194485 ER PT J AU Perlis, RH Ostacher, M Fava, M Nierenberg, AA Sachs, GS Rosenbaum, JF AF Perlis, Roy H. Ostacher, Michael Fava, Maurizio Nierenberg, Andrew A. Sachs, Gary S. Rosenbaum, Jerrold F. TI Assuring That Double-Blind Is Blind SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; CLINICAL-TRIALS; MEDICATION; PATIENT C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Bipolar Clin, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Bipolar Clin, Dept Psychiat, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM rperlis@partners.org OI Ostacher, Michael/0000-0003-0353-7535 NR 10 TC 26 Z9 27 U1 1 U2 3 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 MAR PY 2010 VL 167 IS 3 BP 250 EP 252 DI 10.1176/appi.ajp.2009.09060820 PG 3 WC Psychiatry SC Psychiatry GA 562MR UT WOS:000275056300005 PM 20194487 ER PT J AU Ostacher, MJ Perlis, RH Nierenberg, AA Calabrese, J Stange, JP Salloum, I Weiss, RD Sachs, GS AF Ostacher, Michael J. Perlis, Roy H. Nierenberg, Andrew A. Calabrese, Joseph Stange, Jonathan P. Salloum, Ihsan Weiss, Roger D. Sachs, Gary S. CA STEP-BD Investigators TI Impact of Substance Use Disorders on Recovery From Episodes of Depression in Bipolar Disorder Patients: Prospective Data From the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID 1ST HOSPITALIZATION; ALCOHOL-USE; ABUSE; MANIA; NONADHERENCE; COMORBIDITY; PREDICTORS AB Objective: Bipolar disorder is highly comorbid with substance use disorders, and this comorbidity may be associated with a more severe course of illness, but the impact of comorbid substance abuse on recovery from major depressive episodes in these patients has not been adequately examined. The authors hypothesized that comorbid drug and alcohol use disorders would be associated with longer time to recovery in patients with bipolar disorder. Method: Subjects (N=3,750) with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were followed prospectively for up to 2 years. Prospectively observed depressive episodes were identified for this analysis. Subjects with a past or current drug or alcohol use disorder were compared with those with no history of drug or alcohol use disorders on time to recovery from depression and time until switch to a manic, hypomanic, or mixed episode. Results: During follow up, 2,154 subjects developed a new-onset major depressive episode; of these, 457 subjects switched to a manic, hypomanic, or mixed episode prior to recovery. Past or current substance use disorder did not predict time to recovery from a depressive episode relative to no substance use comorbidity. However, those with current or past substance use disorder were more likely to experience switch from depression directly to a manic, hypomanic, or mixed state. Conclusions: Current or past substance use disorders were not associated with longer time to recovery from depression but may contribute to greater risk of switch into manic, mixed, or hypomanic states. The mechanism conferring this increased risk merits further study. C1 [Ostacher, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. McLean Hosp, Div Alcohol & Drug Abuse, Belmont, MA 02178 USA. RP Ostacher, MJ (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM mostacher@partners.org OI Ostacher, Michael/0000-0003-0353-7535 FU National Institute on Alcoholism and Alcohol Abuse [K23AA016340-01A1]; NIMH [N01MH8001, N01MH80001]; National Institute on Drug Abuse [DA022288, DA15968] FX This study was supported by grant K23AA016340-01A1 from the National Institute on Alcoholism and Alcohol Abuse (Dr. Ostacher), NIMH grant N01MH8001 (Dr. Sachs), and grants DA022288 and DA15968 from the National Institute on Drug Abuse (Dr. Weiss). STEP-BD was funded with Federal funds from NIMH under Contract N01MH80001. Any opinions, findings, and conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the NIMH. NR 23 TC 44 Z9 45 U1 0 U2 4 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 MAR PY 2010 VL 167 IS 3 BP 289 EP 297 DI 10.1176/appi.ajp.2009.09020299 PG 9 WC Psychiatry SC Psychiatry GA 562MR UT WOS:000275056300010 PM 20008948 ER PT J AU Kligerman, S Abbott, G AF Kligerman, Seth Abbott, Gerald TI A Radiologic Review of the New TNM Classification for Lung Cancer SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE International Association for the Study of Lung Cancer (IASLC); lung cancer; staging; TNM ID FORTHCOMING 7TH EDITION; STAGING PROJECT; INTERNATIONAL-ASSOCIATION; BRONCHIOLOALVEOLAR CARCINOMA; SURGICAL RESECTION; MALIGNANT-TUMORS; CHANGING EPIDEMIOLOGY; PROLONGED SURVIVAL; SINGLE INSTITUTION; PROGNOSTIC-FACTORS AB OBJECTIVE. In 2009, a new TNM staging system was published by the International Union Against Cancer and the American Joint Committee on Cancer. The new edition will encompass non-small cell lung cancer, small cell lung cancer, and bronchopulmonary carcinoids. This article will review many important changes that have been made in the revised staging system. CONCLUSION. It is important that radiologists learn the new system and understand the reasons for the changes to provide more accurate clinical staging. C1 [Kligerman, Seth] Univ Maryland, Med Ctr, Dept Diagnost Radiol, Baltimore, MD 21201 USA. [Abbott, Gerald] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Abbott, Gerald] Harvard Univ, Sch Med, Boston, MA USA. RP Kligerman, S (reprint author), Univ Maryland, Med Ctr, Dept Diagnost Radiol, 22 S Greene St,Rm N2W78, Baltimore, MD 21201 USA. EM sethkligerman@hotmail.com NR 59 TC 21 Z9 21 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2010 VL 194 IS 3 BP 562 EP 573 DI 10.2214/AJR.09.3354 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 558KN UT WOS:000274741100006 PM 20173129 ER PT J AU Gee, MS Kim, JY Gervais, DA Hahn, PF Mueller, PR AF Gee, Michael S. Kim, John Y. Gervais, Debra A. Hahn, Peter F. Mueller, Peter R. TI Management of Abdominal and Pelvic Abscesses That Persist Despite Satisfactory Percutaneous Drainage Catheter Placement SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE abscess; catheter; drainage; intervention ID FOLLOW-UP AB OBJECTIVE. The purposes of this study were to determine the frequency with which percutaneous abdominopelvic abscess drainage catheters must be replaced because of inadequate drainage, to assess the effect of percutaneous catheter exchange on clinical outcome, and to determine the predictors of clinical success after catheter exchange. MATERIALS AND METHODS. A database of interventional radiology procedures performed at a single tertiary care hospital from 2001 to 2006 was searched to identify the cases of patients who underwent percutaneous catheter drainage of abdominal or pelvic abscesses that was followed by exchange of the drainage catheter at a later date. The electronic medical records and imaging studies of these patients were retrospectively reviewed to determine the abscess characteristics, details of drainage catheter manipulation, and clinical outcome. RESULTS. Among the 3,027 percutaneous abscess drainage catheters placed, 82 were exchanged because of lack of improvement (imaging evidence of undrained fluid and persistent fever and leukocytosis), for an overall frequency of catheter exchange of 2.7% of abscesses in 3.7% of patients. The success rate of catheter replacement, defined as resolution of the fluid collection without open surgical drainage, was 76.8% (63/82). Prognostic factors favorably influencing the clinical success of catheter exchange included a larger number of drainage catheter sideholes, absence of a fistula, low residual abscess volume after initial catheter drainage, and low CT attenuation of abscess fluid. CONCLUSION. In cases of persistent abscess despite adequate catheter placement, percutaneous catheter exchange over a wire is useful for salvage after the large majority of primary failures. In addition, performance of CT and fluoroscopic catheter injection before catheter exchange facilitates recognition of the predictors of a likely response to catheter exchange. C1 [Gee, Michael S.; Kim, John Y.; Gervais, Debra A.; Hahn, Peter F.; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gee, MS (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Ellison 237, Boston, MA 02114 USA. EM msgee@partners.org NR 13 TC 12 Z9 12 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2010 VL 194 IS 3 BP 815 EP 820 DI 10.2214/AJR.09.3282 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 558KN UT WOS:000274741100042 PM 20173165 ER PT J AU Lim, R AF Lim, Ruth TI Discrepancy Rates of On-Call Radiology Residents' Interpretations of CT Angiography Studies of the Neck and Circle of Willis Reply SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID URINARY-TRACT-INFECTION; VOIDING CYSTOURETHROGRAPHY; VESICOURETERAL REFLUX; CHILDREN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Lim, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 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 MAR PY 2010 VL 194 IS 3 BP W283 EP W283 DI 10.2214/AJR.09.4058 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 558KN UT WOS:000274741100052 PM 20198742 ER PT J AU Wu, JL Seon, JK Gadikota, HR Hosseini, A Sutton, KM Gill, TJ Li, GA AF Wu, Jia-Lin Seon, Jong Keun Gadikota, Hemanth R. Hosseini, Ali Sutton, Karen M. Gill, Thomas J. Li, Guoan TI In Situ Forces in the Anteromedial and Posterolateral Bundles of the Anterior Cruciate Ligament Under Simulated Functional Loading Conditions SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE anterior cruciate ligament; double bundle; in situ force; muscle load ID ANATOMIC DOUBLE-BUNDLE; KNEE FLEXION ANGLES; SEMITENDINOSUS TENDON; VIVO KINEMATICS; 2 GRAFTS; RECONSTRUCTION; 2-BUNDLE; SINGLE; ACL; POSTERIOR AB Background: The in situ forces of the anteromedial (AM) and posterolateral bundles (PL) of the anterior cruciate ligament (ACL) under simulated functional loads such as simulated muscle loads have not been reported. These data are instrumental for improvement of the anatomical double-bundle ACL reconstruction. Hypothesis: The load-sharing patterns of the 2 bundles are complementary under simulated muscle loads. Study Design: Descriptive laboratory study. Methods: Eight cadaveric knees in this study were sequentially studied using a robotic testing system. Each knee was tested under 3 external loading conditions including (1) a 134-N anterior tibial load; (2) combined rotational loads of 10 N.m of valgus and 5 N.m internal tibial torques; and (3) a 400-N quadriceps muscle load with the knee at 0 degrees, 15 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion. The in situ forces of the 2 bundles of ACL were determined using the principle of superposition. Results: Under the anterior tibial load, the PL bundle carried peak loads at full extension and concurrently had significantly lower force than the AM bundle throughout the range of flexion (P < .05). Under the combined rotational loads, the PL bundle contributed to carrying the load between 0 degrees and 30 degrees, although less than the AM bundle. Under simulated muscle loads, both bundles carried loads between 0 degrees and 30 degrees. There was no significant difference between the 2 bundle forces at all flexion angles (P > .05). Conclusion: Under externally applied loads, in general, the AM bundle carried a greater portion of the load at all flexion angles, whereas the PL bundle only shared the load at low flexion angles. The bundles functioned in a complementary rather than a reciprocal manner to each other. Clinical Relevance: The data appear to support the concept that both bundles function in a complementary manner. Thus, how to re-create the 2 bundle functions in an ACL reconstruction should be further investigated. C1 [Wu, Jia-Lin; Seon, Jong Keun; Gadikota, Hemanth R.; Hosseini, Ali; Sutton, Karen M.; Gill, Thomas J.; Li, Guoan] Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. [Wu, Jia-Lin; Seon, Jong Keun; Gadikota, Hemanth R.; Hosseini, Ali; Sutton, Karen M.; Gill, Thomas J.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Jia-Lin] Triserv Gen Hosp, Natl Def Med Ctr, Dept Orthopaed Surg, Taipei, Taiwan. [Seon, Jong Keun] Chonnam Natl Univ, Hwasun Hosp, Dept Orthopaed Surg, Kwangju, South Korea. [Hosseini, Ali] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institutes of Health [AR055612, AR051078] FX The authors gratefully acknowledge the support of the National Institutes of Health (AR055612 & AR051078). NR 33 TC 25 Z9 25 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD MAR PY 2010 VL 38 IS 3 BP 558 EP 563 DI 10.1177/0363546509350110 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 559ED UT WOS:000274803800017 PM 20044500 ER PT J AU Wang, LL Filippi, RZ Zurakowski, D Archibald, T Vargas, SO Voss, SD Shamberger, RC Davies, K Kozakewich, H Perez-Atayde, AR AF Wang, Larry L. Filippi, Renee Zon Zurakowski, David Archibald, Tonora Vargas, Sara O. Voss, Stephan D. Shamberger, Robert C. Davies, Kimberly Kozakewich, Harry Perez-Atayde, Antonio R. TI Effects of Neoadjuvant Chemotherapy on Hepatoblastoma: A Morphologic and Immunohistochemical Study SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE children; hepatocellular carcinoma; cholangiocarcinoma; beta-catenin; cytokeratin; hepatoblastoma ID BETA-CATENIN; CHILDHOOD HEPATOBLASTOMA; THERAPY; RHABDOMYOSARCOMA; TUMORS; FEATURES; CELLS; GENE AB Neoadjuvant chemotherapy followed by resection has become the mainstay in the treatment of hepatoblastoma (HB). The changes after chemotherapy typically result in tumor necrosis and a fibrohistiocytic response. We have observed that treated HBs undergo additional morphologic changes that have not been described. Herein, we report a 15-year retrospective study of HBs in 22 children who received neoadjuvant chemotherapy according to the Children's Oncology Group protocols. The medical records, diagnostic imaging, and histopathology were reviewed. Besides treated HBs having characteristic necrosis and fibrohistiocytic response, two-thirds had areas of cytoarchitectural differentiation ("maturation'') mimicking non-neoplastic liver, and a quarter had alterations mimicking hepatocellular carcinoma. Nuclear expression of beta-catenin and keratin profiles were useful in distinguishing residual tumor with "maturation'' from non-neoplastic liver and therefore in the assessment of surgical margins. Statistical analysis revealed that larger pretreatment and posttreatment imaged tumor size, larger tumor size at pathologic examination, and vascular invasion were significant univariate predictors of metastatic disease, whereas pretreatment imaged tumor size and vascular invasion were also significant independent predictors (multivariate logistic regression analysis). Multifocality, greater posttreatment necrosis and hepatocellular carcinoma-like morphology were more \often associated with metastatic disease, but did not reach statistical significance. C1 [Wang, Larry L.; Filippi, Renee Zon; Archibald, Tonora; Vargas, Sara O.; Kozakewich, Harry; Perez-Atayde, Antonio R.] Childrens Hosp, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Zurakowski, David; Shamberger, Robert C.] Childrens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. [Zurakowski, David] Childrens Hosp, Dana Farber Canc Inst, Dept Anesthesia, Boston, MA 02115 USA. [Davies, Kimberly] Childrens Hosp, Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. [Voss, Stephan D.] Childrens Hosp, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Perez-Atayde, AR (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pathol, 300 Longwood Ave, Boston, MA 02115 USA. EM Antonio.perezatayde@childrens.harvard.edu NR 25 TC 17 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2010 VL 34 IS 3 BP 287 EP 299 DI 10.1097/PAS.0b013e3181ce5f1e PG 13 WC Pathology; Surgery SC Pathology; Surgery GA 570RZ UT WOS:000275697000001 PM 20118773 ER PT J AU Klimstra, DS Modlin, IR Adsay, NV Chetty, R Deshpande, V Gonen, M Jensen, RT Kidd, M Kulke, MH Lloyd, RV Moran, C Moss, SF Oberg, K O'Toole, D Rindi, G Robert, ME Suster, S Tang, LH Tzen, CY Washington, MK Wiedenmann, B Yao, J AF Klimstra, David S. Modlin, Irvin R. Adsay, N. Volkan Chetty, Runjan Deshpande, Vikram Goenen, Mithat Jensen, Robert T. Kidd, Mark Kulke, Matthew H. Lloyd, Ricardo V. Moran, Cesar Moss, Steven F. Oberg, Kjell O'Toole, Dermot Rindi, Guido Robert, Marie E. Suster, Saul Tang, Laura H. Tzen, Chin-Yuan Washington, Mary Kay Wiedenmann, Betram Yao, James TI Pathology Reporting of Neuroendocrine Tumors: Application of the Delphic Consensus Process to the Development of a Minimum Pathology Data Set SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE neuroendocrine tumor; consensus; carcinoid tumor; Delphic; classification ID PANCREATIC ENDOCRINE TUMORS; SMALL-CELL CARCINOMA; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; MOLECULAR TARGETED THERAPY; PROGNOSTIC-FACTORS; GASTROINTESTINAL-TRACT; LOW-GRADE; GASTROENTEROPANCREATIC TUMORS; CLASSIFICATION-SYSTEM; PRECURSOR LESIONS AB Epithelial neuroendocrine tumors (NETs) have been the subject of much debate regarding their optimal classification. Although multiple systems of nomenclature, grading, and staging have been proposed, none has achieved universal acceptance. To help define the underlying common features of these classification systems and to identify the minimal pathology data that should be reported to ensure consistent clinical management and reproducibility of data from therapeutic trials, a multidisciplinary team of physicians interested in NETs was assembled. At a group meeting, the participants discussed a series of "yes'' or "no'' questions related to the pathology of NETs and the minimal data to be included in the reports. After discussion, anonymous votes were taken, using the Delphic principle that 80% agreement on a vote of either yes or no would define a consensus. Questions that failed to achieve a consensus were rephrased once or twice and discussed, and additional votes were taken. Of 108 questions, 91 were answerable either yes or no by more than 80% of the participants. There was agreement about the importance of proliferation rate for tumor grading, the landmarks to use for staging, the prognostic factors assessable by routine histology that should be reported, the potential for tumors to progress biologically with metastasis, and the current status of advanced immunohistochemical and molecular testing for treatment-related biomarkers. The lack of utility of a variety of immunohistochemical stains and pathologic findings was also agreed upon. A consensus could not be reached for the remaining 17 questions, which included both minor points related to extent of disease assessment and some major areas such as terminology, routine immunohistochemical staining for general neuroendocrine markers, use of Ki67 staining to assess proliferation, and the relationship of tumor grade to degree of differentiation. On the basis of the results of the Delphic voting, a minimum pathology data set was developed. Although there remains disagreement among experts about the specific classification system that should be used, there is agreement about the fundamental pathology data that should be reported. Examination of the areas of disagreement reveals significant opportunities for collaborative study to resolve unanswered questions. C1 [Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, Surg Pathol Serv, New York, NY 10065 USA. [Goenen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Modlin, Irvin R.; Kidd, Mark] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [Robert, Marie E.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Adsay, N. Volkan] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. [Chetty, Runjan] Toronto Gen Hosp, Dept Pathol, Toronto, ON, Canada. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jensen, Robert T.] Natl Inst Diabet Digest & Kidney Dis, Bethesda, MD USA. [Lloyd, Ricardo V.] Mayo Clin, Dept Pathol, Rochester, MN USA. [Moran, Cesar] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Yao, James] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Moss, Steven F.] Brown Univ, Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. [Oberg, Kjell] Univ Upsalla, Dept Med Sci, Upsalla, Sweden. [O'Toole, Dermot] St James Hosp, Dept Med, Dublin, Ireland. [O'Toole, Dermot] Trinity Coll Dublin, Dublin, Ireland. [Rindi, Guido] Univ Parma, Dept Pathol & Lab Med, I-43100 Parma, Italy. [Suster, Saul] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. [Tzen, Chin-Yuan] Cathay Gen Hosp, Dept Pathol, Taipei, Taiwan. [Washington, Mary Kay] Vanderbilt Univ Sch Med, Dept Pathol, Nashville, TN USA. [Wiedenmann, Betram] Univ Berlin, Charite Hosp, Dept Internal Med, Berlin, Germany. RP Klimstra, DS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, Surg Pathol Serv, 1275 York Ave, New York, NY 10065 USA. EM klimstrd@mskcc.org RI Gonen, Mithat/E-4826-2012; OI RINDI, Guido/0000-0003-2996-4404 FU Novartis Corporation FX Supported by Novartis Corporation. NR 100 TC 151 Z9 173 U1 0 U2 4 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 MAR PY 2010 VL 34 IS 3 BP 300 EP 313 DI 10.1097/PAS.0b013e3181ce1447 PG 14 WC Pathology; Surgery SC Pathology; Surgery GA 570RZ UT WOS:000275697000002 PM 20118772 ER PT J AU Cerroni, L Barnhill, R Elder, D Gottlieb, G Heenan, P Kutzner, H LeBoit, PE Mihm, M Rosai, J Kerl, H AF Cerroni, Lorenzo Barnhill, Raymond Elder, David Gottlieb, Geoffrey Heenan, Peter Kutzner, Heinz LeBoit, Philip E. Mihm, Martin, Jr. Rosai, Juan Kerl, Helmut TI Melanocytic Tumors of Uncertain Malignant Potential Results of a Tutorial Held at the XXIX Symposium of the International Society of Dermatopathology in Graz, October 2008 SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE atypical Spitz tumor; malignant melanoma; melanocytic tumor of uncertain malignant potential; atypical blue nevus; deep penetrating nevus ID MINIMAL DEVIATION MELANOMA; ATYPICAL SPITZ TUMOR; PIGMENTED-EPITHELIOID-MELANOCYTOMA; SENTINEL LYMPH-NODES; SPINDLE CELL; BLUE NEVUS; NEVI/TUMORS; PERSPECTIVE; DIAGNOSIS; CONSENSUS AB Several reports demonstrated the difficulties and lack of agreement in the histopathologic diagnosis of particular melanocytic tumors (atypical Spitz tumors, atypical blue nevi, deep penetrating nevi). These lesions are often referred to as "melanocytic tumors of uncertain malignant potential'' (MELTUMP). We studied a large number of such tumors to find out whether repeatable histopathologic criteria for distinction of benign from malignant cases exist. Fifty-seven cases of MELTUMP were classified within 3 groups according to behavior as follows: (a) favorable (no evidence of metastatic disease after a follow-up of >= 5 y), (b) unfavorable (tumor-related death and/or large metastatic deposits in the lymph nodes and/or visceral metastases), (c) borderline (small nodal deposits of tumor cells <= 0.2 mm). There were no significant differences in tumor thickness and presence or absence of ulceration between the different groups. The only 3 histopathologic criteria that were statistically different between the groups of favorable and unfavorable cases were presence of mitoses, mitoses near the base, and an inflammatory reaction, all of them found more frequently in cases with unfavorable behavior. The major outcome of this study of a series of "MELTUMPs'' suggests as a preliminary observation that these lesions as a group exist and that they may be biologically different from conventional melanoma and benign melanocytic nevi. The terminology remains highly controversial, reflecting the uncertainty in classification and interpretation of these atypical melanocytic tumors. C1 [Cerroni, Lorenzo; Kerl, Helmut] Med Univ Graz, Dept Dermatol, A-8036 Graz, Austria. [Barnhill, Raymond] Univ Paris 07, Hop St Louis, Dept Dermatol, Paris, France. [Barnhill, Raymond] Univ Paris 07, Hop St Louis, Dept Pathol, Paris, France. [Elder, David] Univ Penn Hlth Syst, Dept Pathol & Lab Med, Philadelphia, PA USA. [Gottlieb, Geoffrey] Ackerman Acad Dermatopathol, New York, NY USA. [LeBoit, Philip E.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [LeBoit, Philip E.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Mihm, Martin, Jr.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Heenan, Peter] Cutaneous Pathol, Nedlands, WA, Australia. [Kutzner, Heinz] Dermatopathol Gemeinschaftslabor, Friedrichshafen, Germany. [Rosai, Juan] Ctr Diagnost Italiano, Ctr Consulenze Anat Patolog, Milan, Italy. RP Cerroni, L (reprint author), Med Univ Graz, Dept Dermatol, Auenbruggerpl 8, A-8036 Graz, Austria. EM lorenzo.cerroni@medunigraz.at NR 37 TC 84 Z9 84 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2010 VL 34 IS 3 BP 314 EP 326 DI 10.1097/PAS.0b013e3181cf7fa0 PG 13 WC Pathology; Surgery SC Pathology; Surgery GA 570RZ UT WOS:000275697000003 PM 20118771 ER PT J AU Snuderl, M Kolman, OK Chen, YB Hsu, JJ Ackerman, AM Dal Cin, P Ferry, JA Harris, NL Hasserjian, RP Zukerberg, LR Abramson, JS Hochberg, EP Lee, H Lee, AI Toomey, CE Sohani, AR AF Snuderl, Matija Kolman, Olga K. Chen, Yi-Bin Hsu, Jessie J. Ackerman, Adam M. Dal Cin, Paola Ferry, Judith A. Harris, Nancy Lee Hasserjian, Robert P. Zukerberg, Lawrence R. Abramson, Jeremy S. Hochberg, Ephraim P. Lee, Hang Lee, Alfred I. Toomey, Christiana E. Sohani, Aliyah R. TI B-cell Lymphomas With Concurrent IGH-BCL2 and MYC Rearrangements Are Aggressive Neoplasms With Clinical and Pathologic Features Distinct From Burkitt Lymphoma and Diffuse Large B-cell Lymphoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE MYC; BCL2; diffuse large B-cell lymphoma; Burkitt lymphoma; cytogenetics; high-grade B-cell lymphoma ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; OF-THE-LITERATURE; POLYMERASE-CHAIN-REACTION; FOLLICULAR LYMPHOMA; C-MYC; POOR-PROGNOSIS; MALIGNANT-LYMPHOMAS; TRANSLOCATIONS; T(14/18) AB B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as "double-hit'' lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathologic features overlapping with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic lymphoma/leukemia (B-LBL). The clinical and pathologic spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined. We conducted a retrospective analysis of clinical and pathologic features of 20 cases of DHL seen at our institution during a 5-year period. In addition, we carried out case-control comparisons of DHL with BL and International Prognostic Index (IPI)-matched DLBCL. The 11 men and 9 women had a median age of 63.5 years (range 32 to 91). Six patients had a history of grade 1 to 2 follicular lymphoma; review of the prior biopsy specimens in 2 of 5 cases revealed blastoid morphology. Eighteen patients had Ann Arbor stage 3 or 4 disease and all had elevated serum lactate dehydrogenase (LDH) levels at presentation. Extranodal disease was present in 17/20 (85%), bone marrow involvement in 10/17 (59%) and central nervous system (CNS) disease in 5/11 (45%). Nineteen patients were treated with combination chemotherapy, of whom 18 received rituximab and 14 received CNS-directed therapy. Fourteen patients (70%) died within 8 months of diagnosis. Median overall survival in the DHL group (4.5 mo) was inferior to both BL (P = 0.002) and IPI-matched DLBCL (P = 0.04) control patients. Twelve DHL cases (60%) were classified as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, 7 cases (35%) as DLBCL, not otherwise specified, and 1 case as B-LBL. Distinguishing features from BL included expression of Bcl2 (P < 0.0001), Mum1/IRF4 (P = 0.006), Ki-67 < 95% (P < 0.0001), and absence of EBV-EBER (P = 0.006). DHL commonly contained the t(8; 22) rather than the t(8; 14) seen in most BL controls (P = 0.001), and exhibited a higher number of chromosomal aberrations (P = 0.0009). DHL is a high-grade B-cell neoplasm with a poor prognosis, resistance to multiagent chemotherapy, and clinical and pathologic features distinct from other high-grade B-cell neoplasms. Familiarity with the morphologic and immunophenotypic spectrum of DHL is important in directing testing to detect concurrent IGH-BCL2 and MYC rearrangements when a karyotype is unavailable. The aggressive clinical behavior and combination of genetic abnormalities seen in these cases may warrant categorization as a separate entity in future classifications and call for novel therapeutic approaches. C1 [Snuderl, Matija; Kolman, Olga K.; Ferry, Judith A.; Harris, Nancy Lee; Hasserjian, Robert P.; Zukerberg, Lawrence R.; Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Hsu, Jessie J.; Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Chen, Yi-Bin; Ackerman, Adam M.; Abramson, Jeremy S.; Hochberg, Ephraim P.; Lee, Alfred I.; Toomey, Christiana E.] Massachusetts Gen Hosp, Ctr Canc, Ctr Hematol Malignancies, Boston, MA USA. [Dal Cin, Paola] Brigham & Womens Hosp, Dept Pathol, Ctr Adv Mol Diagnost, Boston, MA 02115 USA. [Snuderl, Matija; Kolman, Olga K.; Dal Cin, Paola; Ferry, Judith A.; Harris, Nancy Lee; Hasserjian, Robert P.; Zukerberg, Lawrence R.; Sohani, Aliyah R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Hsu, Jessie J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Sohani, AR (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM arsohani@partners.org OI Snuderl, Matija/0000-0003-0752-0917 FU NCI NIH HHS [R37 CA076404]; NIGMS NIH HHS [T32 GM074897, T32 GM074897-07] NR 58 TC 175 Z9 189 U1 1 U2 11 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 MAR PY 2010 VL 34 IS 3 BP 327 EP 340 DI 10.1097/PAS.0b013e3181cd3aeb PG 14 WC Pathology; Surgery SC Pathology; Surgery GA 570RZ UT WOS:000275697000004 PM 20118770 ER PT J AU Mortensen, EM Garcia, S Leykum, L Nakashima, B Restrepo, MI Anzueto, A AF Mortensen, Eric M. Garcia, Sean Leykum, Luci Nakashima, Brandy Restrepo, Marcos I. Anzueto, Antonio TI Association of Hypoglycemia With Mortality for Subjects Hospitalized With Pneumonia SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Pneumonia; Hypoglycemia; Mortality ID COMMUNITY-ACQUIRED PNEUMONIA; ELDERLY-PATIENTS; GLUCOSE; SEPSIS; SEVERITY; OUTCOMES AB Background: Previous research has shown that hypoglycemia is associated with worse outcomes for the elderly, in sepsis, and in children with pneumonia. The purpose of this study was to examine whether hypoglycemia (<70 mg/dL) is associated with increased 30-day mortality, after adjusting for potential confounders, for adults hospitalized with pneumonia. Methods: A retrospective cohort study conducted at 2 tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, and had a chest x-ray consistent with, community-acquired pneumonia. Our primary analysis was a multivariable logistic regression with the dependent variable of 30-day mortality and with independent variable of hypoglycemia, diabetes, severity of illness determined using the pneumonia severity index, and pneumonia-related processes of care. Results: Data were abstracted on 787 subjects at the 2 hospitals. Mortality was 8.1% at 30 days. At presentation, 55% of subjects were at low risk, 33% were at moderate risk, and 12% were at high risk. In our cohort, 2.8% (n = 22) had hypoglycemia at presentation. Unadjusted mortality for those who were hypoglycemic was 27.3% versus 8.6% for those who were not (P = 0.0003). In the multivariable analysis, hypoglycemia (odds ratio: 4.1, 95% confidence interval: 1.4-11.7) was significantly associated with 30-day mortality. Conclusions: After adjusting for severity of illness and other potential confounders, hypoglycemia is significantly associated with 30-day mortality for patients hospitalized with pneumonia. Patients with hypoglycemia should be placed in closely monitored settings even when by pneumonia specific risk systems they would normally be discharged. C1 [Mortensen, Eric M.; Garcia, Sean; Leykum, Luci; Restrepo, Marcos I.; Anzueto, Antonio] ALMD UTHSCSA, S Texas Vet Hlth Care Syst, VERDICT Res Program, Med Serv,Audie L Murphy Div, San Antonio, TX 78229 USA. [Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Div Gen Internal Med, San Antonio, TX 78229 USA. [Restrepo, Marcos I.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Crit Care Med, San Antonio, TX 78229 USA. [Garcia, Sean; Leykum, Luci] Univ Texas Hlth Sci Ctr San Antonio, Hosp Med, San Antonio, TX 78229 USA. RP Mortensen, EM (reprint author), ALMD UTHSCSA, S Texas Vet Hlth Care Syst, VERDICT Res Program, Med Serv,Audie L Murphy Div, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM mortensene@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU Department of Veteran Affairs; Howard Hughes Medical Institute [00378-001]; NHLBI [NO1-HR-16153]; CTSA [KL2 RR025766] FX This study was supported by a Department of Veteran Affairs Veterans Integrated Service Network 17 new faculty grant and a Howard Hughes Medical Institute faculty-start up grant 00378-001 (EMM); in part, by the NHLBI grant NO1-HR-16153 (to AA); by a Department of Veteran Affairs Veterans Integrated Service Network 17 new faculty grant and a CTSA Award Number KL2 RR025766 (to MIR); and supported with resources and the use of facilities at the South Texas Veterans Health Care System. NR 22 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAR PY 2010 VL 339 IS 3 BP 239 EP 243 DI 10.1097/MAJ.0b013e3181ca43fe PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 567CD UT WOS:000275419000009 PM 20220334 ER PT J AU Sis, B Mengel, M Haas, M Colvin, RB Halloran, PF Racusen, LC Solez, K Baldwin, WM Bracamonte, ER Broecker, V Cosio, F Demetris, AJ Drachenberg, C Einecke, G Gloor, J Glotz, D Kraus, E Legendre, C Liapis, H Mannon, RB Nankivell, BJ Nickeleit, V Papadimitriou, JC Randhawa, P Regele, H Renaudin, K Rodriguez, ER Seron, D Seshan, S Suthanthiran, M Wasowska, BA Zachary, A Zeevi, A AF Sis, B. Mengel, M. Haas, M. Colvin, R. B. Halloran, P. F. Racusen, L. C. Solez, K. Baldwin, W. M., III Bracamonte, E. R. Broecker, V. Cosio, F. Demetris, A. J. Drachenberg, C. Einecke, G. Gloor, J. Glotz, D. Kraus, E. Legendre, C. Liapis, H. Mannon, R. B. Nankivell, B. J. Nickeleit, V. Papadimitriou, J. C. Randhawa, P. Regele, H. Renaudin, K. Rodriguez, E. R. Seron, D. Seshan, S. Suthanthiran, M. Wasowska, B. A. Zachary, A. Zeevi, A. TI Banff '09 Meeting Report: Antibody Mediated Graft Deterioration and Implementation of Banff Working Groups SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE Acute allograft rejection; acute cellular rejection; acute rejection; allograft rejection; antibody mediated rejection; Banff; Banff lesions; Banff schema; classification; chronic allograft rejection; donor specific antibody; genomic markers; GeneChip; heart allograft; microarrays; proteomics; pancreas allograft; transplantation ID DONOR-SPECIFIC ANTIBODIES; HUMAN-LEUKOCYTE ANTIGEN; RENAL-ALLOGRAFT PATHOLOGY; POSITIVE CROSS-MATCH; TRANSPLANT GLOMERULOPATHY; KIDNEY-TRANSPLANTATION; C4D DEPOSITION; ACTIVATING ANTIBODIES; CARDIAC TRANSPLANTS; HUMORAL REJECTION AB The 10th Banff Conference on Allograft Pathology was held in Banff, Canada from August 9 to 14, 2009. A total of 263 transplant clinicians, pathologists, surgeons, immunologists and researchers discussed several aspects of solid organ transplants with a special focus on antibody mediated graft injury. The willingness of the Banff process to adapt continuously in response to new research and improve potential weaknesses, led to the implementation of six working groups on the following areas: isolated v-lesion, fibrosis scoring, glomerular lesions, molecular pathology, polyomavirus nephropathy and quality assurance. Banff working groups will conduct multicenter trials to evaluate the clinical relevance, practical feasibility and reproducibility of potential changes to the Banff classification. There were also sessions on quality improvement in biopsy reading and utilization of virtual microscopy for maintaining competence in transplant biopsy interpretation. In addition, compelling molecular research data led to the discussion of incorporation of omics-technologies and discovery of new tissue markers with the goal of combining histopathology and molecular parameters within the Banff working classification in the near future. C1 [Sis, B.; Mengel, M.; Solez, K.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Sis, B.; Mengel, M.; Halloran, P. F.] Univ Alberta, Dept Med, Div Nephrol & Immunol, Alberta Transplant Appl Genom Ctr, Edmonton, AB, Canada. [Haas, M.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Colvin, R. B.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Colvin, R. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Racusen, L. C.; Wasowska, B. A.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Baldwin, W. M., III] Cleveland Clin, Dept Immunol, Lerner Res Inst, Cleveland, OH 44106 USA. [Bracamonte, E. R.] Univ Arizona, Dept Pathol, Tucson, AZ USA. [Broecker, V.] Hannover Med Sch, Dept Pathol, Hannover, Germany. [Cosio, F.; Gloor, J.] Mayo Fdn & Clin, Div Nephrol & Hypertens, Rochester, NY USA. [Demetris, A. J.; Randhawa, P.; Zeevi, A.] Univ Pittsburgh, Dept Pathol, Div Transplantat Pathol, Pittsburgh, PA USA. [Drachenberg, C.; Papadimitriou, J. C.] Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. [Einecke, G.] Hannover Med Sch, Dept Nephrol, Hannover, Germany. [Glotz, D.] Hosp St Louis, Dept Nephrol, Paris, France. [Kraus, E.; Zachary, A.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Legendre, C.] Hop Necker Enfants Malad, Serv Transplantat, Paris, France. [Legendre, C.] Univ Paris 05, Paris, France. [Liapis, H.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO USA. [Mannon, R. B.] Univ Alabama, Div Nephrol, Birmingham, AL USA. [Nankivell, B. J.] Westmead Hosp, Ctr Transplant Res & Renal Res, Sydney, NSW, Australia. [Nickeleit, V.] Univ N Carolina, Dept Lab Med & Pathol, Chapel Hill, NC USA. [Regele, H.] Univ Vienna, Inst Pathol, Vienna, Austria. [Renaudin, K.] CHU Hotel Dieu, Dept Pathol, Nantes, France. [Rodriguez, E. R.] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44106 USA. [Seron, D.] Hosp Gen Valle Hebron, Dept Nephrol, Barcelona, Spain. [Seshan, S.] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. [Suthanthiran, M.] Cornell Univ, Weill Med Coll, Div Nephrol, Dept Med, New York, NY 10021 USA. RP Sis, B (reprint author), Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. EM bsis@ualberta.ca RI Glotz, Denis/F-7881-2011; Halloran, Philip/J-1390-2012 OI Halloran, Philip/0000-0003-1371-1947 NR 49 TC 399 Z9 427 U1 2 U2 21 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2010 VL 10 IS 3 BP 464 EP 471 DI 10.1111/j.1600-6143.2009.02987.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 556VK UT WOS:000274621200007 PM 20121738 ER PT J AU Hirohashi, T Uehara, S Chase, CM DellaPelle, P Madsen, JC Russell, PS Colvin, RB AF Hirohashi, T. Uehara, S. Chase, C. M. DellaPelle, P. Madsen, J. C. Russell, P. S. Colvin, R. B. TI Complement Independent Antibody-Mediated Endarteritis and Transplant Arteriopathy in Mice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Chronic transplant arteriopathy; complement; C4d; heart transplantation ID CHRONIC ALLOGRAFT NEPHROPATHY; MURINE CARDIAC ALLOGRAFTS; CAPILLARY DEPOSITION; ENDOTHELIAL-CELLS; C4D DEPOSITION; HLA ANTIBODIES; CORONARY ATHEROSCLEROSIS; HUMORAL REJECTION; FRAGMENT C4D; MOUSE HEARTS AB Complement fixation, as evidenced by C4d in the microvasculature, is a widely accepted criterion of antibody-mediated rejection. Complement fixation has been shown to be essential in acute antibody-mediated rejection, but its role in chronic rejection has not been addressed. Previous studies showed that passive transfer of complement fixing monoclonal IgG2a anti-H-2Kk into B6.RAG1-/- KO recipients of B10.BR hearts led to progressive chronic transplant arteriopathy (CTA) over 14-28 days, accompanied by C4d deposition. The present studies were designed to test whether complement was required for these lesions. We report that a noncomplement fixing donor-specific alloantibody (DSA, monoclonal IgG1 anti-H-2Kk) injected into B6.RAG1-/- KO recipients of B10.BR hearts also promotes CTA, without C4d deposition. Furthermore, a passive transfer of DSA (monoclonal IgG2a anti-H-2Kk) initiated endarteritis followed by CTA in B6.RAG1-/- mice genetically deficient in the third component of complement (RAG1-/-C3-/-). These studies indicate that antibody to class I MHC antigens can trigger chronic arterial lesions in vivo without complement participation, in contrast to acute antibody-mediated rejection. This pathway may be relevant to C4d-negative chronic rejection sometimes observed in patients with DSA, and argues that lack of C4d deposition does not exclude antibody-mediated chronic rejection. C1 [DellaPelle, P.; Colvin, R. B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hirohashi, T.; Uehara, S.; Chase, C. M.; DellaPelle, P.; Madsen, J. C.; Russell, P. S.; Colvin, R. B.] Harvard Univ, Sch Med, Boston, MA USA. [Hirohashi, T.; Uehara, S.; Chase, C. M.; Madsen, J. C.; Russell, P. S.] Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02114 USA. [Hirohashi, T.; Uehara, S.; Chase, C. M.; Madsen, J. C.; Russell, P. S.] Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Div, Boston, MA 02114 USA. [Uehara, S.] Osaka Univ, Dept Pediat Surg, Grad Sch Med, Osaka, Japan. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM colvin@helix.mgh.harvard.edu FU Roche Organ Transplant Research Foundation; NIH [RO1 HL071932]; American Society of Transplantation FX This work was supported by grants from the Roche Organ Transplant Research Foundation, NIH grant RO1 HL071932 and by a Basic Science Grant from the American Society of Transplantation (TH). NR 44 TC 49 Z9 51 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2010 VL 10 IS 3 BP 510 EP 517 DI 10.1111/j.1600-6143.2009.02958.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 556VK UT WOS:000274621200012 PM 20055805 ER PT J AU Mollov, JL Lucas, CL Haspot, F Kurtz, J Gaspar, C Guzman, A Sykes, M AF Mollov, J. L. Lucas, C. L. Haspot, F. Kurtz, J. Gaspar, C. Guzman, A. Sykes, M. TI Recipient Dendritic Cells, But Not B Cells, Are Required Antigen-Presenting Cells for Peripheral Alloreactive CD8+T-Cell Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Allograft tolerance; anti-CD154 monoclonal antibody; B cell; bone marrow transplantation; CD8; dendritic cell ID CD8(+) T-CELLS; LYMPHOCYTE DEVELOPMENT; TRYPTOPHAN CATABOLISM; MONOCLONAL-ANTIBODY; SELF-TOLERANCE; IN-VIVO; TRANSPLANTATION; DELETION; MARROW; ENGRAFTMENT AB Induction of mixed allogeneic chimerism is a promising approach for achieving donor-specific tolerance, thereby obviating the need for life-long immunosuppression for solid organ allograft acceptance. In mice receiving a low dose (3Gy) of total body irradiation, allogeneic bone marrow transplantation combined with anti-CD154 tolerizes peripheral CD4 and CD8 T cells, allowing achievement of mixed chimerism with specific tolerance to donor. With this approach, peripheral CD8 T-cell tolerance requires recipient MHC class II, CD4 T cells, B cells and DCs. Recipient-type B cells from chimeras that were tolerant to donor still promoted CD8 T-cell tolerance, but their role could not be replaced by donor-type B cells. Using recipients whose B cells or DCs specifically lack MHC class I and/or class II or lack CD80 and CD86, we demonstrate that dendritic cells (DCs) must express CD80/86 and either MHC class I or class II to promote CD8 tolerance. In contrast, B cells, though required, did not need to express MHC class I or class II or CD80/86 to promote CD8 tolerance. Moreover, recipient IDO and IL-10 were not required. Thus, antigen presentation by recipient DCs and not by B cells is critical for peripheral alloreactive CD8 T cell tolerance. C1 [Mollov, J. L.; Lucas, C. L.; Haspot, F.; Kurtz, J.; Gaspar, C.; Guzman, A.; Sykes, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU National Institutes of Health [R01 HL49915, T32DK007540-21]; AST/Wyeth Basic Science; National Defense Science and Engineering; Foundation pour la Recherche Medicale; American Society of Blood and Marrow Transplantation FX This work was supported by National Institutes of Health Grant R01 HL49915. J.L.M. was supported by the 2008 AST/Wyeth Basic Science Fellowship Grant and a National Institutes of Health Training Grant T32DK007540-21. CLL was supported by the National Defense Science and Engineering Graduate Fellowship. FH was supported by fellowships from the Foundation pour la Recherche Medicale and the American Society of Blood and Marrow Transplantation. NR 31 TC 10 Z9 10 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2010 VL 10 IS 3 BP 518 EP 526 DI 10.1111/j.1600-6143.2009.02967.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 556VK UT WOS:000274621200013 PM 20121730 ER PT J AU Gray, KM Watson, NL Carpenter, MJ LaRowe, SD AF Gray, Kevin M. Watson, Noreen L. Carpenter, Matthew J. LaRowe, Steven D. TI N-Acetylcysteine (NAC) in Young Marijuana Users: An Open-Label Pilot Study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Letter ID DOUBLE-BLIND; DEPENDENCE; PLACEBO C1 [Gray, Kevin M.; Watson, Noreen L.; Carpenter, Matthew J.; LaRowe, Steven D.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Carpenter, Matthew J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [LaRowe, Steven D.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Gray, KM (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,POB 250861, Charleston, SC 29425 USA. EM graykm@musc.edu FU NCRR NIH HHS [M01 RR001070, M01 RR001070-31, M01 RR01070]; NIDA NIH HHS [R01 DA026777, K12 DA000357, K12 DA000357-09, K23 DA020482, K23 DA020482-03, R01 DA026777-01] NR 10 TC 45 Z9 47 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAR-APR PY 2010 VL 19 IS 2 BP 187 EP 189 DI 10.1111/j.1521-0391.2009.00027.x PG 3 WC Substance Abuse SC Substance Abuse GA 556VJ UT WOS:000274621100011 PM 20163391 ER PT J AU Cote, CJ AF Cote, Charles J. TI Safety After Chloral Hydrate Sedation of Former Preterm and Term Infants for Magnetic Resonance Imaging: Are the Data Clear? SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID POSTOPERATIVE APNEA; ADVERSE SEDATION; RISK-FACTORS; CHILDREN; EVENTS; MANAGEMENT; PEDIATRICS; RECOVERY; IMPROVE C1 [Cote, Charles J.] Massachusetts Gen Hosp, MassGeneral Hosp Children, Div Pediat Anesthesia, Boston, MA 02114 USA. [Cote, Charles J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Management, Boston, MA USA. RP Cote, CJ (reprint author), Massachusetts Gen Hosp, MassGeneral Hosp Children, Div Pediat Anesthesia, 55 Fruit St, Boston, MA 02114 USA. EM cjcote@partners.org NR 19 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAR PY 2010 VL 110 IS 3 BP 671 EP 673 DI 10.1213/ANE.0b013e3181cd4428 PG 3 WC Anesthesiology SC Anesthesiology GA 563MS UT WOS:000275137200009 PM 20185647 ER PT J AU Reust, DL Reeves, ST Abernathy, JH Dixon, JA Gaillard, WF Mukherjee, R Koval, CN Stroud, RE Spinale, FG AF Reust, Daryl L. Reeves, Scott T. Abernathy, James H., III Dixon, Jennifer A. Gaillard, William F., II Mukherjee, Rupak Koval, Christine N. Stroud, Robert E. Spinale, Francis G. TI Temporally and Regionally Disparate Differences in Plasmin Activity by Tranexamic Acid SO ANESTHESIA AND ANALGESIA LA English DT Article ID EPSILON-AMINOCAPROIC ACID; CARDIAC-SURGERY; CARDIOPULMONARY BYPASS; BLOOD-TRANSFUSION; RENAL-FAILURE; REPERFUSION; FIBRINOLYSIS; METAANALYSIS; THROMBOSIS; INHIBITOR AB BACKGROUND: A major complication associated with cardiac surgery is excessive and prolonged bleeding in the perioperative period. Improving coagulation by inhibiting fibrinolysis, primarily through inhibition of plasmin activity (PLact) with antifibrinolytics such as tranexamic acid (TXA), has been a pharmacological mainstay in cardiac surgical patients. Despite its almost ubiquitous use, the temporal and regional modulation of PLact profiles by TXA remains unexplored. Accordingly, we developed a fluorogenic-microdialysis system to measure in vivo dynamic changes in PLact after TXA administration in a large animal model. METHODS: Pigs (25-35 kg) were randomly assigned to receive TXA (30 mg/kg, diluted into 50 mL normal saline; n = 9) or vehicle (50 mL normal saline; n = 7). Microdialysis probes were placed in the liver, myocardium, kidney, and quadriceps muscle compartments. The microdialysate infusion contained a validated plasmin-specific fluorogenic peptide. The fluorescence emission (standard fluorogenic units [SFU]) of the interstitial fluid collected from the microdialysis probes, which directly reflects PLact, was determined at steady-state baseline and 30, 60, 90, and 120 min after TXA/vehicle infusion. Plasma PLact was determined at the same time points using the same fluorogenic substrate approach. RESULTS: TXA reduced plasma PLact at 30 min after infusion by >110 SFU compared with vehicle values (P < 0.05). Specifically, there was a decrease in liver PLact at 90 and 120 min after TXA infusion of >150 SFU (P < 0.05) and 175 SFU (P < 0.05), respectively. The decrease in liver PLact occurred 60 min after the maximal decrease in plasma PLact. In contrast, kidney, heart, and quadriceps PLact transiently increased followed by an overall decrease at 120 min. CONCLUSIONS: Using a large animal model and in vivo microdialysis measurements of PLact, the unique findings from this study were 2-fold. First, TXA induced temporally distinct PLact profiles within the plasma and selected interstitial compartments. Second, TXA caused region-specific changes in PLact profiles. These temporal and regional differences in the effects of TXA may have important therapeutic considerations when managing fibrinolysis in the perioperative period. (Anesth Analg 2010; 110: 694-701) C1 [Spinale, Francis G.] Med Univ S Carolina, Dept Cardiothorac Surg, Div Cardiothorac Surg, Charleston, SC 29403 USA. [Reust, Daryl L.; Reeves, Scott T.; Abernathy, James H., III] Med Univ S Carolina, Dept Anesthesiol & Perioperat Med, Charleston, SC 29403 USA. [Dixon, Jennifer A.; Gaillard, William F., II; Mukherjee, Rupak; Koval, Christine N.; Stroud, Robert E.; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Dept Cardiothorac Surg, Div Cardiothorac Surg, Strom Thurmond Res Bldg,114 Doughty St,Room 625, Charleston, SC 29403 USA. EM wilburnm@musc.edu FU NIH [HL059165, HL078650]; Veterans' Affairs Health Administration FX Supported in part by NIH grants HL059165 and HL078650 and a Merit Award form the Veterans' Affairs Health Administration. NR 32 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAR PY 2010 VL 110 IS 3 BP 694 EP 701 DI 10.1213/ANE.0b013e3181c7eb27 PG 8 WC Anesthesiology SC Anesthesiology GA 563MS UT WOS:000275137200012 PM 20185649 ER PT J AU Almeida-Chen, G Niezgoda, J Diaz-Gomez, JL Motta, P AF Almeida-Chen, Gracie Niezgoda, Julie Diaz-Gomez, Jose L. Motta, Pablo TI The Role of Echocardiography in the Management of an Embolized Atrial Septal Helex (R) Occluder SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID PATENT FORAMEN OVALE; PULMONARY-ARTERY; CLOSURE C1 [Motta, Pablo] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat Cardiovasc Anesthesiol, Houston, TX 77030 USA. [Almeida-Chen, Gracie] Cleveland Clin, Dept Cardiothorac Anesthesiol, Cleveland, OH 44106 USA. [Niezgoda, Julie] Cleveland Clin, Dept Pediat & Congenital Heart Anesthesiol, Cleveland, OH 44106 USA. [Diaz-Gomez, Jose L.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Motta, P (reprint author), Texas Childrens Hosp, Baylor Coll Med, Dept Pediat Cardiovasc Anesthesiol, 6621 Fannin,WT 17417 B, Houston, TX 77030 USA. EM pxmotta@texaschildrens.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAR PY 2010 VL 110 IS 3 BP 734 EP 736 DI 10.1213/ANE.0b013e3181cb3edc PG 3 WC Anesthesiology SC Anesthesiology GA 563MS UT WOS:000275137200022 PM 20042445 ER PT J AU Schmidt, U Bittner, E Pivi, S Marota, JJA AF Schmidt, Ulrich Bittner, Edward Pivi, Silvia Marota, John J. A. TI Hemodynamic Management and Outcome of Patients Treated for Cerebral Vasospasm with Intraarterial Nicardipine and/or Milrinone SO ANESTHESIA AND ANALGESIA LA English DT Article ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; CLINICAL-EXPERIENCE; NIMODIPINE; THERAPY; EFFICACY; DEFICITS; SAFETY AB BACKGROUND: Vasospasm is a potentially devastating complication after aneurysmal subarachnoid hemorrhage. Although endovascular treatment with intraarterial nicardipine and milrinone is an accepted clinical treatment strategy, there is little information either on hemodynamic management during treatment or on outcome and consequences of the hemodynamic management. We tested 2 hypotheses: (1) intraarterial administration of nicardipine and milrinone to treat cerebral vasospasm would require increased administration of vasoconstrictor to support arterial blood pressure at target levels; and (2) high-dose vasopressors administered to increase blood pressure in these patients would lead to systemic acidosis and end-organ ischemic damage. METHODS: We conducted a single-center, retrospective review of consecutive patients with clinically symptomatic vasospasm after aneurysmal subarachnoid hemorrhage that failed medical management with "triple H therapy" and subsequently received intraarterial nicardipine and/or milrinone between March 2005 and July 2007. RESULTS: Of 160 endovascular interventions in 73 patients (aged 52 +/- 10 years; 50 women), 96 received only nicardipine, 5 only milrinone, and 59 both drugs. General anesthesia with muscle relaxation was performed for 93% of procedures. During treatment, both the number and dose of vasopressors required to maintain arterial blood pressure at target levels increased; the median dose of phenylephrine increased from 200 (n = 121) to 325 mu g/min (n = 122), norepinephrine increased from 12 (n = 60) to 24.5 mu g/min (n = 87), and vasopressin infusions increased from 7 to 24. Nonetheless, arterial blood pressure decreased 13% during treatment. In >90% of procedures, the postprocedure angiogram showed improved vessel caliber. A single patient demonstrated troponin T increase; no patients had a decrease in renal function, bowel or peripheral ischemia, systemic acidosis, or acute stroke. Overall mortality was 11%. CONCLUSIONS: Intraarterial administration of nicardipine and/or milrinone requires use of vasopressors to maintain arterial blood pressure. Despite high doses of vasoconstrictors, treatment has low mortality, minimal end-organ ischemic damage or systemic acidosis, and results in improved caliber of cerebral vessels affected by vasospasm. (Anesth Analg 2010;110:895-902) C1 [Schmidt, Ulrich; Bittner, Edward; Pivi, Silvia; Marota, John J. A.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Schmidt, Ulrich; Bittner, Edward; Pivi, Silvia; Marota, John J. A.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Marota, JJA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,GRJ-422, Boston, MA 02114 USA. EM jmarota@partners.org NR 23 TC 22 Z9 26 U1 0 U2 1 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 MAR PY 2010 VL 110 IS 3 BP 895 EP 902 DI 10.1213/ANE.0b013e3181cc9ed8 PG 8 WC Anesthesiology SC Anesthesiology GA 563MS UT WOS:000275137200046 PM 20185665 ER PT J AU Cappiello, E O'Rourke, N Segal, S Tsen, LC AF Cappiello, Eric O'Rourke, Nollag Segal, Scott Tsen, Lawrence C. TI Are the Conclusions Supported by the Statistics? Response SO ANESTHESIA AND ANALGESIA LA English DT Letter C1 [Cappiello, Eric; O'Rourke, Nollag; Segal, Scott; Tsen, Lawrence C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Cappiello, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. EM ltsen@zeus.bwh.harvard.edu NR 2 TC 1 Z9 1 U1 0 U2 1 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 MAR PY 2010 VL 110 IS 3 BP 969 EP 969 DI 10.1213/ANE.0b013e3181c8f778 PG 1 WC Anesthesiology SC Anesthesiology GA 563MS UT WOS:000275137200059 ER PT J AU Scholz, J Yaksh, TL AF Scholz, Joachim Yaksh, Tony L. TI Preclinical Research on Persistent Postsurgical Pain What We Don't Know, but Should Start Studying SO ANESTHESIOLOGY LA English DT Editorial Material ID POSTOPERATIVE PAIN; NEUROPATHIC PAIN; ANIMAL-MODELS; PREVENTION; EXPRESSION; ALLODYNIA; CONSENSUS; SURGERY C1 [Scholz, Joachim] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA. [Yaksh, Tony L.] Univ Calif San Diego, Dept Anesthesiol & Pharmacol, La Jolla, CA 92093 USA. RP Scholz, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA. EM scholz.joachim@mgh.harvard.edu FU NIDA NIH HHS [R01 DA002110-29, R01 DA002110]; NINDS NIH HHS [R01 NS050408-03, R01 NS050408, R01 NS016541, R37 NS016541, R01 NS016541-23] NR 14 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2010 VL 112 IS 3 BP 511 EP 513 DI 10.1097/ALN.0b013e3181cf4266 PG 3 WC Anesthesiology SC Anesthesiology GA 565CN UT WOS:000275266800002 PM 20124975 ER PT J AU Kehlet, H Rathmell, JP AF Kehlet, Henrik Rathmell, James P. TI Persistent Postsurgical Pain The Path Forward through Better Design of Clinical Studies SO ANESTHESIOLOGY LA English DT Editorial Material ID PREVENTION C1 [Kehlet, Henrik] Univ Copenhagen Hosp, Rigshosp, Sect Surg Pathophysiol, DK-2100 Copenhagen, Denmark. [Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Kehlet, H (reprint author), Univ Copenhagen Hosp, Rigshosp, Sect Surg Pathophysiol, DK-2100 Copenhagen, Denmark. EM jrathmell@partners.org NR 7 TC 56 Z9 57 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2010 VL 112 IS 3 BP 514 EP 515 DI 10.1097/ALN.0b013e3181cf423d PG 2 WC Anesthesiology SC Anesthesiology GA 565CN UT WOS:000275266800003 PM 20124977 ER PT J AU Yu, BL Shahid, M Egorina, EM Sovershaev, MA Raher, MJ Lei, C Wu, MX Bloch, KD Zapol, WM AF Yu, Binglan Shahid, Mohd Egorina, Elena M. Sovershaev, Mikhail A. Raher, Michael J. Lei, Chong Wu, Mei X. Bloch, Kenneth D. Zapol, Warren M. TI Endothelial Dysfunction Enhances Vasoconstriction Due to Scavenging of Nitric Oxide by a Hemoglobin-based Oxygen Carrier SO ANESTHESIOLOGY LA English DT Article ID SICKLE-CELL-DISEASE; HEMORRHAGIC-SHOCK; HIGH-FAT; BLOOD; HYPERTENSION; SUBSTITUTES; RESISTANCE; DEATH; RISK; MICE AB Background: To date, there is no safe and effective hemoglobin-based oxygen carrier (HBOC) to substitute for erythrocyte transfusion. It is uncertain whether a deficiency of endothelial nitric oxide bioavailability (endothelial dysfunction) prevents or augments HBOC-induced vasoconstriction. Methods: Hemodynamic effects of infusion of PolyHeme (1.08 g hemoglobin/kg; Northfield Laboratories, Evanston, IL) or murine tetrameric hemoglobin (0.48 g hemoglobin/kg) were determined in awake healthy lambs, awake mice, and anesthetized mice. In vitro, a cumulative dose-tension response was obtained by sequential addition of PolyHeme or tetrameric hemoglobin to phenylephrine-precontracted murine aortic rings. Results: Infusion of PolyHeme did not cause systemic hypertension in awake lambs but produced acute systemic and pulmonary vasoconstriction. Infusion of PolyHeme did not cause systemic hypertension in healthy wild-type mice but induced severe systemic vasoconstriction in mice with endothelial dysfunction (either db/db mice or high-fat fed wild-type mice for 4-6 weeks). The db/db mice were more sensitive to systemic vasoconstriction than wild-type mice after the infusion of either tetrameric hemoglobin or PolyHeme. Murine aortic ring studies confirmed that db/db mice have an impaired response to an endothelial-dependent vasodilator and an enhanced vasoconstrictor response to HBOC. Conclusions: Reduction in low molecular weight hemoglobin concentrations to less than 1% is insufficient to abrogate the vasoconstrictor effects of HBOC infusion in healthy awake sheep or in mice with reduced vascular nitric oxide levels associated with endothelial dysfunction. These findings suggest that testing HBOCs in animals with endothelial dysfunction can provide a more sensitive indication of their potential vasoconstrictor effects. C1 [Yu, Binglan; Shahid, Mohd; Egorina, Elena M.; Sovershaev, Mikhail A.; Raher, Michael J.; Lei, Chong; Wu, Mei X.; Bloch, Kenneth D.; Zapol, Warren M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, 55 Fruit St,Thier 503, Boston, MA 02114 USA. EM wzapol@partners.org FU U.S. Public Health Service, National Institutes of Health, Bethesda, Maryland [HL-42397] FX Received from Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Submitted for publication July 13, 2009. Accepted for publication November 18, 2009. Supported by U.S. Public Health Service Grant HL-42397 from the National Institutes of Health, Bethesda, Maryland (to Dr. Zapol). Dr. Zapol receives royalties on patents licensed by Massachusetts General Hospital to Linde Corporation, Munich, Germany, and Ikaria, Clinton, New Jersey, on inhaled nitric oxide. Dr. Bloch has received grants from Ikaria and Linde to study inhaled nitric oxide. Northfield Corp. (Evanston, Illinois) funded the animal charges and provided the PolyHeme at no cost. NR 17 TC 37 Z9 38 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2010 VL 112 IS 3 BP 586 EP 594 DI 10.1097/ALN.0b013e3181cd7838 PG 9 WC Anesthesiology SC Anesthesiology GA 565CN UT WOS:000275266800014 PM 20179495 ER PT J AU Cotten, JF Forman, SA Laha, JK Cuny, GD Husain, S Miller, KW Nguyen, HH Kelly, EW Stewart, D Liu, AP Raines, DE AF Cotten, Joseph F. Forman, Stuart A. Laha, Joydev K. Cuny, Gregory D. Husain, Shaukat Miller, Keith W. Nguyen, Hieu H. Kelly, Elizabeth W. Stewart, Deirdre Liu, Aiping Raines, Douglas E. TI Carboetomidate A Pyrrole Analog of Etomidate Designed Not to Suppress Adrenocortical Function SO ANESTHESIOLOGY LA English DT Article ID CRITICALLY-ILL PATIENTS; CARCINOMA-CELL-LINE; ANESTHETIC ETOMIDATE; CRYSTAL-STRUCTURE; INHIBITION; INDUCTION; RESPONSES; IMIDAZOLE; BINDING; COORDINATION AB Background: Etomidate is a sedative hypnotic that is often used in critically ill patients because it provides superior hemodynamic stability. However, it also binds with high affinity to 11 beta-hydroxylase, potently suppressing the synthesis of steroids by the adrenal gland that are necessary for survival. The authors report the results of studies to define the pharmacology of (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate), a pyrrole analog of etomidate specifically designed not to bind with high affinity to 11 beta-hydroxylase. Methods: The hypnotic potency of carboetomidate was defined in tadpoles and rats using loss of righting reflex assays. Its ability to enhance wild-type alpha(1)beta(2)gamma(2l) and etomidate-insensitive mutant alpha(1)beta(2)M286W gamma(2l) human gamma-aminobutyric acid type A receptor activities was assessed using electrophysiologic techniques. Its potency for inhibiting in vitro cortisol synthesis was defined using a human adrenocortical cell assay. Its effects on in vivo hemodynamic and adrenocortical function were defined in rats. Results: Carboetomidate was a potent hypnotic in tadpoles and rats. It increased currents mediated by wild-type but not etomidate-insensitive mutant gamma-aminobutyric acid type A receptors. Carboetomidate was a three orders of magnitude less-potent inhibitor of in vitro cortisol synthesis by adrenocortical cells than was etomidate. In rats, carboetomidate caused minimal hemodynamic changes and did not suppress adrenocortical function at hypnotic doses. Conclusions: Carboetomidate is an etomidate analog that retains many beneficial properties of etomidate, but it is dramatically less potent as an inhibitor of adrenocortical steroid synthesis. Carboetomidate is a promising new sedative hypnotic for potential use in critically ill patients in whom adrenocortical suppression is undesirable. C1 [Cotten, Joseph F.; Forman, Stuart A.; Laha, Joydev K.; Cuny, Gregory D.; Husain, Shaukat; Miller, Keith W.; Nguyen, Hieu H.; Kelly, Elizabeth W.; Stewart, Deirdre; Liu, Aiping; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRB444, Boston, MA 02114 USA. EM draines@partners.org FU National Institutes of Health, Bethesda, Maryland [R01-GM087316, P01-GM58448]; Foundation for Anesthesia Education and Research, Rochester, Minnesota; Partners Healthcare, Boston, Massachusetts; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts FX Received from the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Submitted for publication August 23, 2009. Accepted for publication December 8, 2009. Supported by grants R01-GM087316 and P01-GM58448 from the National Institutes of Health, Bethesda, Maryland; the Foundation for Anesthesia Education and Research, Rochester, Minnesota; Partners Healthcare, Boston, Massachusetts; and the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. The Massachusetts General Hospital has submitted a patent application for carboetomidate and related analogs. Six authors (Raines, Cotten, Forman, Cuny, Husain, and Miller), and their respective laboratories, departments, and institutions could receive royalties relating to the development or sale of these drugs. NR 35 TC 32 Z9 36 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2010 VL 112 IS 3 BP 637 EP 644 DI 10.1097/ALN.0b013e3181cf40ed PG 8 WC Anesthesiology SC Anesthesiology GA 565CN UT WOS:000275266800020 PM 20179500 ER PT J AU Costa, ELV Musch, G Winkler, T Schroeder, T Harris, RS Jones, HA Venegas, JG Melo, MFV AF Costa, Eduardo L. V. Musch, Guido Winkler, Tilo Schroeder, Tobias Harris, R. Scott Jones, Hazel A. Venegas, Jose G. Melo, Marcos F. Vidal TI Mild Endotoxemia during Mechanical Ventilation Produces Spatially Heterogeneous Pulmonary Neutrophilic Inflammation in Sheep SO ANESTHESIOLOGY LA English DT Article ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; FREQUENCY OSCILLATORY VENTILATION; TIDAL VOLUMES; REGIONAL VENTILATION; CYTOKINE RESPONSE; KINETICS; LIPOPOLYSACCHARIDE; MODEL; PET AB Background: There is limited information on the regional inflammatory effects of mechanical ventilation and endotoxemia on the production of acute lung injury. Measurement of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake with positron emission tomography allows for the regional, in vivo and noninvasive, assessment of neutrophilic inflammation. The authors tested whether mild endotoxemia combined with large tidal volume mechanical ventilation bounded by pressures within clinically acceptable limits could yield measurable and anatomically localized neutrophilic inflammation. Methods: Sheep were mechanically ventilated with plateau pressures = 30-32 cm H(2)O and positive end-expiratory pressure = 0 for 2 h. Six sheep received intravenous endotoxin (10 ng.kg(-1).min(-1)), whereas six did not (controls), in sequentially performed studies. The authors imaged with positron emission tomography the intrapulmonary kinetics of infused (13)N-nitrogen and (18)F-FDG to compute regional perfusion and (18)F-FDG uptake. Transmission scans were used to assess aeration. Results: Mean gas fraction and perfusion distribution were similar between groups. In contrast, a significant increase in (18)F-FDG uptake was observed in all lung regions of the endotoxin group. In this group, (18)F-FDG uptake in the middle and dorsal regions was significantly larger than that in the ventral regions. Multivariate analysis showed that the (18)F-FDG uptake was associated with regional aeration (P < 0.01) and perfusion (P < 0.01). Conclusions: Mild short-term endotoxemia in the presence of heterogeneous lung aeration and mechanical ventilation with pressures within clinically acceptable limits produces marked spatially heterogeneous increases in pulmonary neutrophilic inflammation. The dependence of inflammation on aeration and perfusion suggests a multifactorial basis for that finding. 18F-FDG uptake may be a sensitive marker of pulmonary neutrophilic inflammation in the studied conditions. C1 [Musch, Guido; Winkler, Tilo; Venegas, Jose G.; Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Harris, R. Scott] Harvard Univ, Sch Med, Boston, MA USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM mvidalmelo@partners.org RI Winkler, Tilo/B-5337-2009; OI Winkler, Tilo/0000-0002-7276-5550; Schroeder, Tobias/0000-0002-4439-8060 FU National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland [HL 5R01HL086827, K08HL076464] FX Received from Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Submitted for publication April 6, 2009. Accepted for publication November 18, 2009. Supported by the National Heart, Lung, and Blood Institute from the National Institutes of Health, Bethesda, Maryland (grant HL 5R01HL086827), and by the National Institutes of Health grant K08HL076464 (to G. M.). Presented in part at the Annual Meeting of the American Society of Anesthesiologists, Orlando, Florida, October 18, 2008. NR 55 TC 33 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2010 VL 112 IS 3 BP 658 EP 669 DI 10.1097/ALN.0b013e3181cbd1d4 PG 12 WC Anesthesiology SC Anesthesiology GA 565CN UT WOS:000275266800023 PM 20179503 ER PT J AU Givrad, TK Maarek, JMI Moore, WH Holschneider, DP AF Givrad, Tina K. Maarek, Jean-Michel I. Moore, William H. Holschneider, Daniel P. TI Powering an Implantable Minipump with a Multi-layered Printed Circuit Coil for Drug Infusion Applications in Rodents SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Electromagnetic field; Class-E oscillator; Infusion pump; Printed coil; Radio frequency identification device ID CHALLENGE; RATS AB We report the use of a multi-layer printed coil circuit for powering (36-94 mW) an implantable microbolus infusion pump (MIP) that can be activated remotely for use in drug infusion in nontethered, freely moving small animals. This implantable device provides a unique experimental tool with applications in the fields of animal behavior, pharmacology, physiology, and functional brain imaging. Two different designs are described: a battery-less pump usable when the animal is inside a home-cage surrounded by a primary inductive coil and a pump powered by a rechargeable battery that can be used for studies outside the home-cage. The use of printed coils for powering of small devices by inductive power transfer presents significant advantages over similar approaches using hand-wound coils in terms of ease of manufacturing and uniformity of design. The high efficiency of a class-E oscillator allowed powering of the minipumps without the need for close physical contact of the primary and secondary coils, as is currently the case for most devices powered by inductive power transfer. C1 [Givrad, Tina K.; Maarek, Jean-Michel I.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Moore, William H.] Univ So Calif, Alfred E Mann Inst, Los Angeles, CA 90089 USA. [Holschneider, Daniel P.] Univ So Calif, Dept Psychiat, Los Angeles, CA 90089 USA. [Holschneider, Daniel P.] Univ So Calif, Dept Neurol, Los Angeles, CA 90089 USA. [Holschneider, Daniel P.] Univ So Calif, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA. [Holschneider, Daniel P.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Holschneider, Daniel P.] Greater Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. RP Givrad, TK (reprint author), Univ So Calif, Dept Biomed Engn, 1042 Downey Way 140, Los Angeles, CA 90089 USA. EM givrad@usc.edu FU NIBIB [1 RO1 NS050171] FX Supported by the NIBIB (1 RO1 NS050171). We would like to thank Drs. Jun Yang, Zhou Wang and Theodore Sadler and Ms. Yumei Guo for their contributions NR 15 TC 8 Z9 8 U1 0 U2 4 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 MAR PY 2010 VL 38 IS 3 BP 707 EP 713 DI 10.1007/s10439-009-9876-x PG 7 WC Engineering, Biomedical SC Engineering GA 571JA UT WOS:000275746900015 PM 20033778 ER PT J AU Ahuja, SS AF Ahuja, Seema S. TI Quantification of plaque volume by micro-CT techniques SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Meeting Abstract C1 [Ahuja, Seema S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Ahuja, Seema S.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC CLINICAL SCIENTISTS PI MIDDLEBURY PA PO BOX 1287, MIDDLEBURY, VT 05753 USA SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD SPR PY 2010 VL 40 IS 2 MA 25 BP 192 EP 192 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 588CC UT WOS:000277043100039 ER PT J AU Pollak, DD Rogan, MT Egner, T Perez, DL Yanagihara, TK Hirsch, J AF Pollak, Daniela D. Rogan, Michael T. Egner, Tobias Perez, David L. Yanagihara, Ted K. Hirsch, Joy TI A translational bridge between mouse and human models of learned safety SO ANNALS OF MEDICINE LA English DT Article DE Amygdala; dorsolateral prefrontal cortex; functional magnetic resonance imaging (fMRI); learned safety; translational research ID MAJOR DEPRESSION; INCREASED AMYGDALA; COGNITIVE CONTROL; BRAIN; FMRI; FEAR; ANXIETY; CORTEX AB Background. Learned safety is established by negatively correlating the occurrence of a neutral stimulus and a noxious stimulus, which renders the previously neutral stimulus a 'safety signal'. While the neurophysiological and molecular mechanisms have been characterized in mice, it is currently not known how the neural substrates involved compare between mice and people. Methods. Here we attempt to adapt the original animal protocol to humans and use functional magnetic resonance imaging to examine neural responses to the conditioned stimulus in safety conditioned and fear conditioned subjects. Diffusion tensor imaging (DTI) was used in a parallel group of subjects as a first approach to delineate the underlying neural circuitry. Results. Learned safety is associated with dampened amygdala and increased dorsolateral prefrontal cortex and caudate responses and paralleled by pupillary constriction. A neural connection between the amygdala and the dorsolateral prefrontal cortex is suggested by DTI. Conclusion. We present a translational bridge between mouse and human models of learned safety in which cellular and molecular insights from animal experiments are extended to the human neural circuitry. This study provides an example of how animal experiments can be used to inform and target human studies, which in turn can corroborate results obtained in experimental animals. C1 [Pollak, Daniela D.] Med Univ Vienna, Ctr Physiol & Pharmacol, Dept Physiol, A-1090 Vienna, Austria. [Pollak, Daniela D.; Rogan, Michael T.; Hirsch, Joy] Columbia Univ, Dept Neurosci, New York, NY USA. [Rogan, Michael T.; Yanagihara, Ted K.; Hirsch, Joy] Columbia Univ, PICS, Program Imaging & Cognit Sci, New York, NY USA. [Egner, Tobias] Duke Univ, Dept Psychol & Neuroscince, Ctr Cognit Neurosci, Durham, NC 27706 USA. [Perez, David L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Perez, David L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hirsch, Joy] Columbia Univ, Dept Radiol, New York, NY USA. [Hirsch, Joy] Columbia Univ, Dept Psychol, New York, NY 10027 USA. RP Pollak, DD (reprint author), Med Univ Vienna, Ctr Physiol & Pharmacol, Dept Physiol, Schwarzspanierstr 17, A-1090 Vienna, Austria. EM daniela.pollak@meduniwien.ac.at RI Egner, Tobias/A-5237-2009; OI Egner, Tobias/0000-0001-7956-3241; Hirsch, Joy/0000-0002-1418-6489 FU Austrian Academy of Science; Austrian Science Fund; Columbia University; Columbia University Medical School FX Daniela D. Pollak was supported by the Austrian Academy of Science (Max-Kade-Fellowship) and the Austrian Science Fund (Erwin-SchroedingerFellowship). Tobias Egner was supported by a Columbia University fMRI Research Fellowship. Ted Yanagihara was supported by the Medical Scientist Training Program, Columbia University Medical School. Imaging funds were provided by education grants to Joy Hirsch, Director, fMRI Research Center, Columbia University (now PICS, Program for Imaging & Cognitive Sciences) for translational and applied studies. The extremely skillful and dedicated expertise of Stephen Dashnaw in carrying out the imaging experiments is highly appreciated. NR 28 TC 24 Z9 24 U1 2 U2 9 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 EI 1365-2060 J9 ANN MED JI Ann. Med. PD MAR PY 2010 VL 42 IS 2 BP 115 EP U10 DI 10.3109/07853890903583666 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 560LZ UT WOS:000274905500003 PM 20121549 ER PT J AU Rentz, DM Locascio, JJ Becker, JA Moran, EK Eng, E Buckner, RL Sperling, RA Johnson, KA AF Rentz, Dorene M. Locascio, Joseph J. Becker, John A. Moran, Erin K. Eng, Elisha Buckner, Randy L. Sperling, Reisa A. Johnson, Keith A. TI Cognition, Reserve, and Amyloid Deposition in Normal Aging SO ANNALS OF NEUROLOGY LA English DT Article ID PITTSBURGH COMPOUND-B; POSITRON-EMISSION-TOMOGRAPHY; ADULT READING TEST; ALZHEIMERS-DISEASE; PREMORBID INTELLIGENCE; OLDER PERSONS; ELDERLY SUBJECTS; HEALTHY-YOUNG; DEMENTIA; MEMORY AB Objective: To determine whether amyloid deposition is associated with impaired neuropsychological (NP) performance and whether cognitive reserve (CR) modifies this association. Methods: In 66 normal elderly controls and 17 patients with Alzheimer disease (AD), we related brain retention of Pittsburgh Compound B (PiB) to NP performance and evaluated the impact of CR using education and American National Adult Reading Test intelligence quotient as proposed proxies. Results: We found in the combined sample of subjects that PiB retention in the precuneus was inversely related to NP performance, especially in tests of memory function, but also in tests of working memory, semantic processing, language, and visuospatial perception. CR significantly modified the relationship, such that at progressively higher levels of CR, increased amyloid deposition was less or not at all associated with poorer neuropsychological performance. In a subsample of normal controls, both the main effect of amyloid deposition of worse memory performance and the interaction with CR were replicated using a particularly challenging memory test. Interpretation: Amyloid deposition is associated with lower cognitive performance both in AD patients and in the normal elderly, but the association is modified by CR, suggesting that CR may be protective against amyloid-related cognitive impairment. ANN NEUROL 2010;67:353-364 C1 [Rentz, Dorene M.; Locascio, Joseph J.; Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Rentz, Dorene M.; Eng, Elisha; Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02114 USA. [Locascio, Joseph J.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Becker, John A.; Moran, Erin K.; Buckner, Randy L.; Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Boston, MA 02114 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Boston, MA 02114 USA. [Buckner, Randy L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Buckner, Randy L.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Buckner, Randy L.] Howard Hughes Med Inst, Cambridge, MA USA. RP Johnson, KA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Div Nucl Med & Mol Imaging, White 427,33 Fruit St, Boston, MA 02114 USA. OI Kennedy, Kristen/0000-0001-5373-9026 FU National Institute on Aging [AG027435-S1, AG00513421, AG021910]; Howard Hughes Medical Institute; Alzheimer Association [HRG-06-32444, HRG-08-90934]; Charles H. Farnsworth Trust, Boston Massachusetts FX This work was supported by the National Institute on Aging (grant AG027435-S1, R.A.S., KA.J.; grant AG00513421, R.A.S., KA.J.; and grant AG021910, R.L.B.), an anonymous medical foundation the Howard Hughes Medical Institute (R.L.B.), the Alzheimer Association HRG-06-32444 (grant HRG-06-32444, R.A.S., KA.J. and grant HRG-08-90934, D.M.R., KA.J.), and the Charles H. Farnsworth Trust, Boston Massachusetts (D.M.R.). NR 73 TC 187 Z9 189 U1 6 U2 23 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 MAR PY 2010 VL 67 IS 3 BP 353 EP 364 DI 10.1002/ana.21904 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577IS UT WOS:000276216800011 PM 20373347 ER PT J AU Glover, LE Newton, K Krishnan, G Bronson, R Boyle, A Krivickas, LS Brown, RH AF Glover, Louise E. Newton, Kimberly Krishnan, Gomathi Bronson, Roderick Boyle, Alexandra Krivickas, Lisa S. Brown, Robert H., Jr. TI Dysferlin Overexpression in Skeletal Muscle Produces a Progressive Myopathy SO ANNALS OF NEUROLOGY LA English DT Article ID GIRDLE MUSCULAR-DYSTROPHY; ENDOPLASMIC-RETICULUM STRESS; ADENOASSOCIATED VIRAL VECTORS; MIYOSHI MYOPATHY; IN-VITRO; MEMBRANE REPAIR; TRANSGENIC MICE; ACTIN GENE; EXPRESSION; PROTEIN AB Objective: The dose-response effects of dysferlin transgenesis were analyzed to determine if the dysferlin-deficient myopathies are good candidates for gene replacement therapy. Methods: We have generated 3 lines of transgenic mice, expressing low, mid, and high levels of full-length human dysferlin from a muscle-specific promoter. Transgenic skeletal muscle was analyzed and scored for morphological and functional deficits. Results: Overexpression of dysferlin in mice resulted in a striking phenotype of kyphosis, irregular gait, and reduced muscle mass and strength. Moreover, protein dosage correlated with phenotype severity. In contrast to dysferlin-null skeletal muscle, no evidence of sarcolemmal impairment was revealed. Rather, increased levels of Ca(2+)-regulated, dysferlin-binding proteins and endoplasmic reticulum stress chaperone proteins were observed in muscle lysates from transgenic mice as compared with controls. Interpretation: Expression levels of dysferlin are important for appropriate function without deleterious or cytotoxic effects. As a corollary, we propose that future endeavors in gene replacement for correction of dysferlinopathy should be tailored to take account of this. ANN NEUROL 2010;67:384-393 C1 [Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Glover, Louise E.; Newton, Kimberly; Boyle, Alexandra; Brown, Robert H., Jr.] Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA USA. [Glover, Louise E.] Univ Colorado Denver, Dept Gastroenterol & Hepatol, Aurora, CO USA. [Krishnan, Gomathi; Krivickas, Lisa S.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Bronson, Roderick] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. RP Brown, RH (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, 55 Lake Ave N, Worcester, MA 01655 USA. EM Robert.Brown@umassmed.edu FU CB Day Company; NIH (National Institute of Neurological Diseases and Stroke); Muscular Dystrophy Association [MDA 4062] FX This study was supported by the CB Day Company, the NIH (National Institute of Neurological Diseases and Stroke), and the Muscular Dystrophy Association (MDA 4062). NR 44 TC 22 Z9 22 U1 0 U2 1 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 MAR PY 2010 VL 67 IS 3 BP 384 EP 393 DI 10.1002/ana.21926 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577IS UT WOS:000276216800014 PM 20373350 ER PT J AU Gardner, RC Schmahmann, JD AF Gardner, Raquel C. Schmahmann, Jeremy D. TI Arginine Test Is Not Reliable for Diagnosing Cerebellar Multiple System Atrophy SO ANNALS OF NEUROLOGY LA English DT Article ID GROWTH-HORMONE-SECRETION; ADULT-ONSET ATAXIA; BODY-MASS INDEX; PARKINSONS-DISEASE; PROGRESSION; ETIOLOGY AB We evaluated the arginine growth hormone (GH) stimulation test for the diagnosis of cerebellar-type multiple system atrophy (MSAc) in patients with ataxia. Fourteen subjects with MSAc, 11 with idiopathic late-onset cerebellar ataxia (ILOCA), 10 with familial ataxia, and 10 healthy controls were tested. After pituitary GH deficiency was excluded, subjects underwent arginine testing. Peak serum GH response was analyzed. No significant differences in peak GH response were found between subject populations. Thirty-three percent of MSAc subjects mounted responses >10 mu g/l GH. Thirty-six percent of ILOCA subjects and 40 percent of healthy controls mounted responses <4 mu g/l GH. Arginine thus appears to be unreliable for the diagnosis of MSAc. ANN NEUROL 2010;67:404-408 C1 [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM jschmahmann@partners.org FU Doris Duke Clinical Research Fellowship Program; Harvard Medical School Pasteur Program and Office of Enrichment Programs; Birmingham Foundation; Mallinkrodt General Clinical Research Center at Massachusetts General Hospital FX This research was supported by the Doris Duke Clinical Research Fellowship Program (RCG), the Harvard Medical School Pasteur Program and Office of Enrichment Programs (RCG), the Birmingham Foundation (JDS), and the Mallinkrodt General Clinical Research Center at Massachusetts General Hospital (RCG, JDS). NR 20 TC 4 Z9 4 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 MAR PY 2010 VL 67 IS 3 BP 404 EP 408 DI 10.1002/ana.21898 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577IS UT WOS:000276216800017 PM 20373353 ER PT J AU Oh, B Butow, P Mullan, B Clarke, S Beale, P Pavlakis, N Kothe, E Lam, L Rosenthal, D AF Oh, B. Butow, P. Mullan, B. Clarke, S. Beale, P. Pavlakis, N. Kothe, E. Lam, L. Rosenthal, D. TI Impact of Medical Qigong on quality of life, fatigue, mood and inflammation in cancer patients: a randomized controlled trial SO ANNALS OF ONCOLOGY LA English DT Article DE cancer; fatigue; inflammation; mood; quality of life ID FUNCTIONAL ASSESSMENT; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; THERAPY; CHEMOTHERAPY; PROGRAM; SYMPTOMS; EXERCISE; STRESS; OUTPATIENTS AB Background: Substantial numbers of cancer patients use complementary medicine therapies, even without a supportive evidence base. This study aimed to evaluate in a randomized controlled trial, the use of Medical Qigong (MQ) compared with usual care to improve the quality of life (QOL) of cancer patients. Patients and methods: One hundred and sixty-two patients with a range of cancers were recruited. QOL and fatigue were measured by Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Fatigue, respectively, and mood status by Profile of Mood State. The inflammatory marker serum C-reactive protein (CRP) was monitored serially. Results: Regression analysis indicated that the MQ group significantly improved overall QOL (t(144) = 25.761, P < 0.001), fatigue (t(153) = 25.621, P < 0.001), mood disturbance (t(122) = 2.346, P = 0.021) and inflammation (CRP) (t(99) = 2.042, P < 0.044) compared with usual care after controlling for baseline variables. Conclusions: This study indicates that MQ can improve cancer patients' overall QOL and mood status and reduce specific side-effects of treatment. It may also produce physical benefits in the long term through reduced inflammation. C1 [Oh, B.; Clarke, S.; Beale, P.; Pavlakis, N.] Univ Sydney, Concord Repatriat Gen Hosp, Dept Med, Concord, NSW 2139, Australia. [Oh, B.; Butow, P.; Mullan, B.] Univ Sydney, Sch Psychol, Ctr Med Psychol & Evidence Based Decis Making, Sydney, NSW 2006, Australia. [Oh, B.; Clarke, S.; Beale, P.] Concord Repatriat Gen Hosp, Sydney Canc Ctr, Sydney, NSW, Australia. [Pavlakis, N.] Royal N Shore Hosp, Dept Med Oncol, Sydney, NSW, Australia. [Kothe, E.] Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia. [Lam, L.] Univ Notre Dame, Sch Med Sydney, Notre Dame, IN 46556 USA. [Rosenthal, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Oh, B (reprint author), Univ Sydney, Concord Repatriat Gen Hosp, Dept Med, Concord, NSW 2139, Australia. EM bsoh@med.usyd.edu.au RI Kothe, Emily/M-7888-2013; OI Kothe, Emily/0000-0003-1210-0554; Mullan, Barbara/0000-0002-0177-8899 NR 34 TC 52 Z9 53 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2010 VL 21 IS 3 BP 608 EP 614 DI 10.1093/annonc/mdp479 PG 7 WC Oncology SC Oncology GA 575DE UT WOS:000276045300026 PM 19880433 ER PT J AU Rubino, F Kaplan, LM Schauer, PR Cummings, DE AF Rubino, Francesco Kaplan, Lee M. Schauer, Philip R. Cummings, David E. CA Diabet Surg Summit Delegates TI The Diabetes Surgery Summit Consensus Conference Recommendations for the Evaluation and Use of Gastrointestinal Surgery to Treat Type 2 Diabetes Mellitus SO ANNALS OF SURGERY LA English DT Article ID ROUX-EN-Y; MALABSORPTIVE GASTRIC BYPASS; BARIATRIC SURGERY; MORBID-OBESITY; NONTEACHING HOSPITALS; SURGICAL OUTCOMES; WEIGHT-LOSS; MELLITUS; MORTALITY; DEFICIENCIES AB Objectives: To develop guidelines for the use of gastrointestinal surgery to treat type 2 diabetes and to craft an agenda for further research. Background: Increasing evidence demonstrates that bariatric surgery can dramatically ameliorate type 2 diabetes. Not surprisingly, gastrointestinal operations are now being used throughout the world to treat diabetes in association with obesity, and increasingly, for diabetes alone. However, the role for surgery in diabetes treatment is not clearly defined and there are neither clear guidelines for these practices nor sufficient plans for clinical trials to evaluate the risks and benefits of such "diabetes surgery." Methods: A multidisciplinary group of 50 voting delegates from around the world gathered in Rome, Italy for the first International Conference on Gastrointestinal Surgery to Treat Type 2 Diabetes-(the "Diabetes Surgery Summit"). During the meeting, available scientific evidence was examined and critiqued by the entire group to assess the strength of evidence and to draft consensus statements. Through an iterative process, draft statements were then serially discussed, debated, edited, reassessed, and finally presented for formal voting. After the Rome meeting, statements that achieved consensus were summarized and distributed to all voting delegates for further input and final approval. These statements were then formally critiqued by representatives of several sientific societies at the 1st World Congress on Interventional Therapies for T2DM (New York, Sept 2008). Input from this discussion was used to generate the current position statement. Results: A Diabetes Surgery Summit (DSS) Position Statement consists of recommendations for clinical and research issues, as well as general concepts and definitions in diabetes surgery. The DSS recognizes the legitimacy of surgical approaches to treat diabetes in carefully selected patients. For example, gastric bypass was deemed a reasonable treatment option for patients with poorly controlled diabetes and a body mass index >= 30 kg/m(2). Clinical trials to investigate the exact role of surgery in patients with less severe obesity and diabetes are considered a priority. Furthermore, investigations on the mechanisms of surgical control of diabetes are strongly encouraged, as they may help advance the understanding of diabetes pathophysiology. Conclusions: The DSS consensus document embodies the foundations of "diabetes surgery," and represents a timely attempt by leading scholars to improve access to surgical options supported by sound evidence, while also preventing harm from inappropriate use of unproven procedures. C1 [Rubino, Francesco] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Surg, Surg Metab Sect, New York, NY USA. [Rubino, Francesco] Univ Cattolica Sacro Cuore, Rome, Italy. [Kaplan, Lee M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston Obes & Nutrician Res Ctr, Boston, MA USA. [Schauer, Philip R.] Cleveland Clin, Lerner Coll Med, Bariatr & Metab Inst, Cleveland, OH 44106 USA. [Cummings, David E.] Univ Washington, VA Puget Sound Hlth Care Syst & Diabet, Obes Ctr Excellence, Dept Med & Diabet,Div Metab, Seattle, WA 98195 USA. RP Rubino, F (reprint author), Cornell Univ, Weill Cornell Med Coll, 525 E 68th St,P-714, New York, NY 10065 USA. EM frr2007@med.cornell.edu FU Covidien; Ethicon; Allergan; Storz; GI Dynamics; Roche; Amylin; Power Medical Interventions FX DSS was supported by a generous grants from the following sponsors: Covidien, Ethicon, Allergan, Storz, GI Dynamics, Roche, Amylin, Power Medical Interventions. NR 44 TC 164 Z9 190 U1 1 U2 14 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 MAR PY 2010 VL 251 IS 3 BP 399 EP 405 DI 10.1097/SLA.0b013e3181be34e7 PG 7 WC Surgery SC Surgery GA 562OD UT WOS:000275060800003 PM 19934752 ER PT J AU Partelli, S Fernandez-Del Castillo, C Bassi, C Mantovani, W Thayer, SP Crippa, S Ferrone, CR Falconi, M Pederzoli, P Warshaw, AL Salvia, R AF Partelli, Stefano Fernandez-Del Castillo, Carlos Bassi, Claudio Mantovani, William Thayer, Sarah P. Crippa, Stefano Ferrone, Cristina R. Falconi, Massimo Pederzoli, Paolo Warshaw, Andrew L. Salvia, Roberto TI Invasive Intraductal Papillary Mucinous Carcinomas of the Pancreas Predictors of Survival and the Role of Lymph Node Ratio SO ANNALS OF SURGERY LA English DT Article ID INDEPENDENT PROGNOSTIC-FACTOR; CLINICOPATHOLOGICAL FEATURES; DUCTAL ADENOCARCINOMA; CANCER REGARDLESS; CYSTIC NEOPLASMS; GASTRIC-CANCER; RESECTION; NUMBER; CLASSIFICATION; EXPERIENCE AB Introduction: Intraductal papillary mucinous neoplasms (IPMNs) are being increasingly recognized, and often harbor cancer. Lymph node metastases are an important prognostic factor for patients with invasive intraductal papillary carcinoma (I-IPMC), but the role of lymph node ratio (LNR) in predicting survival after surgery for I-IPMC is unknown. Methods: The combined databases from the Surgical Department of Massachusetts General Hospital of Boston and the University of Verona were queried. We retrospectively reviewed clinical and pathologic data of all patients with resected, pathologically confirmed, I-IPMC between 1990 and 2007. Univariate and multivariate analysis were performed. Results: I-IPMCs were diagnosed in 104 patients (55 males and 49 females), median age was 69 years. Recurrent disease was identified in 49 patients (47.1%) and the median 5-year disease specific survival (DSS) was 60.1%. The median number of resected/ evaluated nodes was 15 (range, 5-60). There were 60 (57.7%) patients who had negative lymph nodes (N0), whereas 44 (42.3%) had lymph node metastases (N1). Patients with lymph node metastases had a shorter 5-year DSS (28.9%) compared with patients with negative lymph nodes (80.3%; P < 0.05) As the LNR increased, 5-year DSS decreased (LNR = 0, 86.5%; LNR >0 to 0.2, 34.4%; LNR >0.2, 11.1%; P < 0.05). On multivariate analysis, LNR, the presence of a family history of pancreatic cancer and a preoperative value of Ca 19.9 > 37 U/L were significant predictors of survival (P < 0.05). Conclusions: Lymph node ratio is a strong predictor of survival after resection for invasive intraductal papillary mucinous carcinoma. C1 [Partelli, Stefano; Bassi, Claudio; Crippa, Stefano; Falconi, Massimo; Pederzoli, Paolo; Salvia, Roberto] Univ Verona, Dept Surg, I-37100 Verona, Italy. [Fernandez-Del Castillo, Carlos; Thayer, Sarah P.; Ferrone, Cristina R.; Warshaw, Andrew L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Mantovani, William] Univ Verona, Dept Publ Hlth, I-37100 Verona, Italy. RP Salvia, R (reprint author), Policlin GB Rossi, Piazzale LA Scuro, I-37134 Verona, Italy. EM roberto.salvia@medicina.univr.it OI Falconi, Massimo/0000-0001-9654-7243 FU NCI NIH HHS [P01 CA117969, P01 CA117969-04, P01 CA117969-04S1, P01 CA117969-05, P50 CA127003, P50 CA127003-03, P50 CA127003-04]; NIDDK NIH HHS [K08 DK071329-04, K08 DK071329, K08 DK071329-05] NR 33 TC 26 Z9 28 U1 1 U2 4 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 MAR PY 2010 VL 251 IS 3 BP 477 EP 482 DI 10.1097/SLA.0b013e3181cf9155 PG 6 WC Surgery SC Surgery GA 562OD UT WOS:000275060800015 PM 20142730 ER PT J AU Raval, MV Bilimoria, KY Bentrem, DJ Stewart, AK Winchester, DP Ko, CY Reynolds, M AF Raval, Mehul V. Bilimoria, Karl Y. Bentrem, David J. Stewart, Andrew K. Winchester, David P. Ko, Clifford Y. Reynolds, Marleta TI Nodal Evaluation in Wilms' Tumors Analysis of the National Cancer Data Base SO ANNALS OF SURGERY LA English DT Article ID UNITED-STATES; QUALITY ASSESSMENT; COLON-CANCER; PROGNOSIS; CHILDREN; METASTASES; MANAGEMENT; SURVIVAL; STUDY-5; CARE AB Objective: We used a large US clinical cancer registry to assess nodal evaluation performance in children with Wilms' Tumors (WT), to determined factors associated with nodal evaluation, and to define the prognostic importance of nodal status. Summary Background Data: Lymph node assessment remains a part of accurate staging and helps determine therapy for patients with WT. Lack of nodal assessment has been noted but not well studied. Methods: Patients (0-18 years) with WT from the National Cancer Data Base (1985-2001) were assessed for nodal evaluation. Logistic regression was used to identify factors associated with the likelihood of lymph node evaluation. Survival was estimated using the Kaplan-Meier method. Cox regression was used to estimate the risk of mortality. Results: Of 3593 patients, 1510 (42%) had no lymph nodes evaluated by pathology and reported to the National Cancer Data Base. Of 2083 patients who had lymph nodes assessed, 535 (25.7%) had positive nodes. Patients age 2 years or younger, with larger tumor size, and treated at a higher volume center were more likely to have nodes assessed (P < 0.01). Patients who had nodes evaluated had a better 5-year survival compared with those who did not have nodes evaluated (92.2% vs. 88.1%, P < 0.001). In Cox regression, nodal metastases (P < 0.001; HR: 2.2, CI: 1.6-3.0) were associated with increased risk of death after adjusting for patient, tumor, and hospital characteristics. Conclusions: Many patients do not have lymph nodes evaluated during WT resection. Opportunities exist for improved staging and possibly survival in patients with WT through better nodal assessment. C1 [Raval, Mehul V.; Bilimoria, Karl Y.; Stewart, Andrew K.; Winchester, David P.; Ko, Clifford Y.] Amer Coll Surg, Canc Programs, Div Res & Optimal Patient Care, Chicago, IL USA. [Raval, Mehul V.; Reynolds, Marleta] Childrens Mem Hosp, Div Pediat Surg, Chicago, IL 60614 USA. [Raval, Mehul V.; Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Div Gastrointestinal & Oncol Surg, Chicago, IL 60611 USA. [Bentrem, David J.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Winchester, David P.] N Shore Univ Hlth Syst, Dept Surg, Evanston, 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), 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM m-raval@md.northwestern.edu 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 Supported by the John Gray Research Fellowship and the Daniel F. and Ada L. Rice Foundation (to M. V. R.), a career development award from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (D.J.B.). The National Cancer Data Base is supported by the American College of Surgeons, Commission on Cancer, and the American Cancer Society. NR 45 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAR PY 2010 VL 251 IS 3 BP 559 EP 565 DI 10.1097/SLA.0b013e3181cc95d7 PG 7 WC Surgery SC Surgery GA 562OD UT WOS:000275060800028 PM 20083995 ER PT J AU Rauh-Hain, JA Olawaiye, AB Munro, EG Ko, E Alarcon, IA Del Carmen, MG Duska, L AF Rauh-Hain, J. Alejandro Olawaiye, Alexander B. Munro, Elizabeth G. Ko, Emily Alarcon, Irma A. Del Carmen, Marcela G. Duska, Linda TI Role of Computed Tomography in the Surgical Management of Patients with Bowel Obstruction Secondary to Recurrent Ovarian Carcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID INTESTINAL-OBSTRUCTION; PALLIATIVE SURGERY; PROGNOSTIC FACTORS; CANCER; CT; DIAGNOSIS AB The purpose of this study was to evaluate the potential role of preoperative computed tomography (CT) and clinical features for predicting the outcome of patients with bowel obstruction secondary to ovarian cancer. We identified a subpopulation of patients admitted to the Massachusetts General Hospital for bowel obstruction caused by recurrent ovarian cancer from January 1, 1995, to August 1, 2007. A retrospective review of 10 clinical features and 6 radiographic findings was performed. These findings were analyzed as variables with probable prognostic influence on survival and ability to predict successful palliation, defined as the ability to tolerate a regular or low-residue diet 60 days after discharge. Statistical significance was evaluated using the Fisher exact test. Univariate analysis was done by constructing probability curves according to the Kaplan-Meier method and comparing them by the log-rank test. The study population consisted of 55 patients. Absence of carcinomatosis on CT scan and albumin a parts per thousand yen3 g/dL were found to be able to predict successful palliation. Platinum resistance, albumin a parts per thousand yen3 g/dL, and peritoneal carcinomatosis on CT scan were identified as variables with prognostic influence on survival in the univariate analysis. In the Cox regression analysis, only the absence of CT findings of carcinomatosis (P = .009) and albumin a parts per thousand yen 3 g/dL (P = .05) were independently associated with survival. CT scan seems to be helpful in patients with a solitary site as the cause of bowel obstruction. All the patients in our study with this finding had a successful palliation. On the other hand, successful palliation is still feasible in the presence of peritoneal carcinomatosis on CT scan; therefore, this finding alone should not be the reason to avoid surgery in well-selected patients. C1 [Rauh-Hain, J. Alejandro; Munro, Elizabeth G.; Ko, Emily; Del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02115 USA. [Olawaiye, Alexander B.] Univ Pittsburgh, Med Ctr, Magee Womens Hosp, Div Gynecol Oncol, Pittsburgh, PA USA. [Alarcon, Irma A.] Tufts Univ, Sch Med, St Elizabeths Med Ctr, Dept Med, Boston, MA 02111 USA. [Duska, Linda] Univ Virginia, Div Gynecol Oncol, Charlottesville, VA USA. RP Rauh-Hain, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02115 USA. EM lrd5d@hscmail.mcc.virginia.edu NR 23 TC 3 Z9 3 U1 0 U2 1 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 MAR PY 2010 VL 17 IS 3 BP 853 EP 860 DI 10.1245/s10434-009-0813-x PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 554ST UT WOS:000274455400027 PM 20183913 ER PT J AU Liberman, M Muzikansky, A Wright, CD Wain, JC Donahue, DM Allan, JS Gaissert, HA Morse, CR Mathisen, DJ Lanuti, M AF Liberman, Moishe Muzikansky, Alona Wright, Cameron D. Wain, John C. Donahue, Dean M. Allan, James S. Gaissert, Henning A. Morse, Christopher R. Mathisen, Douglas J. Lanuti, Michael TI Incidence and Risk Factors of Persistent Air Leak After Major Pulmonary Resection and Use of Chemical Pleurodesis SO ANNALS OF THORACIC SURGERY LA English DT Article ID AUTOLOGOUS BLOOD PATCH; WATER SEAL; REDUCTION SURGERY; RANDOMIZED-TRIAL; UPPER LOBECTOMY; LUNG RESECTION; CHEST TUBES; PREDICTORS; SUCTION; MANAGEMENT AB Background. Persistent air leak (PAL; defined as air leak > 5 days) after major pulmonary resection is prevalent and associated with significant morbidity. This study examines an incompletely characterized treatment for the management of PAL, chemical pleurodesis. Methods. A retrospective case-control study examining all isolated lobectomies and bilobectomies by thoracotomy was performed. The PALs (1997 to 2006) and controls (2002 to 2006) were identified from a prospective database. Incidence, risk factors, management, and outcome were defined. Results. Over 9 years, 78 PALs were identified in 1,393 patients (5.6%). Controls consisted of 700 consecutive patients. Propensity score analysis matching case and controls showed no predictive risk factors for air leak using a logistic regression model. Univariate analysis demonstrated that female gender, smoking history, and forced vital capacity were predictive risk factors. Treatment of PAL consisted of observation (n = 33, 42.3%), pleurodesis (n = 41, 52.6%), Heimlich valve (n = 3, 3.8%), and reoperation (n = 1, 1.3%). Seventy-three patients (93.6%) required no further intervention. One patient required a muscle flap, one readmission for pneumothorax, and one empyema resulting in death. Sclerosis was successful in 40 of 41 patients (97.6%). Mean time to treatment was 8.4 +/- 3.6 days, mean duration of air leak was 10.7 +/- 4.5, and mean duration of air leak postsclerotherapy was 2.8 +/- 2.2 days. Postoperative pneumonia occurred with increased frequency in PAL patients (6 of 45 [13.3%] vs 34 of 700 [4.9%], p = 0.014). PAL was associated with increased length of stay (14.2 vs 7.1 days, p < 0.001) and time with chest tube (11.5 vs 3.4 days, p < 0.001). Conclusions. Air leaks remain an important cause of morbidity. Pleurodesis is an effective option in management of PAL after major pulmonary resection. (Ann Thorac Surg 2010;89:891-8) (C) 2010 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Biostat, Boston, MA 02114 USA. RP Lanuti, M (reprint author), 55 Fruit St,Blake 1570, Boston, MA 01748 USA. EM mlanuti@partners.org FU Division of Thoracic Surgery at the Massachusetts General Hospital FX Financial support for this study was provided by the Division of Thoracic Surgery at the Massachusetts General Hospital. We would like to acknowledge our data manager and research coordinator, Sheila Cann and Diane Davies, respectively, for their diligence and dedication toward compiling and maintaining the Thoracic Surgery Database. NR 40 TC 14 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2010 VL 89 IS 3 BP 891 EP 898 DI 10.1016/j.athoracsur.2009.12.012 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 558JF UT WOS:000274736800032 PM 20172150 ER PT J AU Salm, TJV Toran, AJ AF Salm, Thomas J. Vander Toran, Ann J. TI An Aortic Cinch to Quell Suture Line Bleeding SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material AB Bleeding from an aortic suture line or cannula site may be difficult to control, especially in the patient with a fragile or dilated aorta. This method of wrapping a vascular graft around the aorta to relieve tension on the suture line and control bleeding is simple and effective, and it facilitates obtaining the proper tension of the wrapped graft. (Ann Thorac Surg 2010; 89: 990-1) (C) 2010 by The Society of Thoracic Surgeons C1 [Salm, Thomas J. Vander] N Shore Med Ctr, Dept Surg, Salem, MA 01970 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Salm, TJV (reprint author), N Shore Med Ctr, Dept Surg, 81 Highland Ave, Salem, MA 01970 USA. EM tvandersalm@partners.org NR 2 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2010 VL 89 IS 3 BP 990 EP 991 DI 10.1016/j.athoracsur.2009.04.131 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 558JF UT WOS:000274736800064 ER PT J AU Wiederhold, NP Najvar, LK Bocanegra, R Graybill, JR Patterson, TF AF Wiederhold, Nathan P. Najvar, Laura K. Bocanegra, Rosie Graybill, John R. Patterson, Thomas F. TI Efficacy of Posaconazole as Treatment and Prophylaxis against Fusarium solani SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CELL TRANSPLANT RECIPIENTS; IN-VITRO ACTIVITIES; ORAL POSACONAZOLE; INVASIVE ASPERGILLOSIS; HEMATOLOGIC MALIGNANCY; AMPHOTERICIN-B; PHARMACOKINETICS; VORICONAZOLE; TRIAZOLES; INFECTION AB Invasive fusariosis is a highly aggressive fungal infection associated with high mortality in heavily immunocompromised patients. Although posaconazole is efficacious as salvage therapy against infections caused by Fusarium species, concerns remain regarding this agent in the setting of reduced potency. To evaluate the efficacy of posaconazole as treatment or prophylaxis against invasive fusariosis caused by Fusarium solani, we utilized a neutropenic murine model of disseminated disease. ICR mice were administered escalating doses of posaconazole (6.25, 12.5, 25, or 50 mg/kg of body weight twice daily [BID]) by oral gavage beginning 2 days prior to inoculation in the prophylaxis studies or beginning 12 h after inoculation as treatment. Therapy was continued until day 9 postinoculation, and animals were monitored off therapy until day 15 for survival. Fungal burden was assessed as CFU in the kidneys. A clear dose-response relationship was observed, as the highest dose of posaconazole (50 mg/kg) was the most effective in prolonging survival and reducing tissue fungal burden both as prophylaxis and as treatment. This dose response was associated with high posaconazole serum concentrations as measured by bioassay. However, the extent of efficacy was also dependent on the infecting inoculum, as greater increases in survival and reductions in fungal burden were observed with the lower inocula tested. In this model high dosages of posaconazole were effective as treatment and prophylaxis against disseminated fusariosis caused by F. solani. C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Graybill, John R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Najvar, Laura K.; Bocanegra, Rosie; Graybill, John R.; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, PERC 6220,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU Schering-Plough, Inc.; Schering-Plough; Pfizer; Merck; Basilea; CyDex; Nektar Therapeutics FX This study was funded by Schering-Plough, Inc.; N. P. W. has received research support from Schering-Plough, Pfizer, Merck, Basilea, and CyDex. T. F. P. has received research support from Merck, Basilea, Pfizer, Schering-Plough, and Nektar Therapeutics; has received speaker fees from Merck and Pfizer; and has served as a consultant for Basilea, Merck, Pfizer, and Toyama. NR 22 TC 11 Z9 11 U1 0 U2 1 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 MAR PY 2010 VL 54 IS 3 BP 1055 EP 1059 DI 10.1128/AAC.01445-09 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 558HY UT WOS:000274733300012 PM 20065054 ER PT J AU Leuckfeld, I Paster, BJ Kristoffersen, AK Olsen, I AF Leuckfeld, Inga Paster, Bruce J. Kristoffersen, Anne K. Olsen, Ingar TI Diversity of Veillonella spp. from subgingival plaque by polyphasic approach SO APMIS LA English DT Article DE Cellular fatty acids; SDS-PAGE; RAPD; 16S rRNA gene; rpoB gene; sequencing ID OBSTRUCTIVE PULMONARY-DISEASE; 16S RIBOSOMAL-RNA; SP-NOV.; GENUS VEILLONELLA; CYSTIC-FIBROSIS; DENTAL PLAQUE; BACTERIA; TAXONOMY AB In a biofilm such as the subgingival microflora, strain-specific properties or factors induced by the host may impart a survival advantage to some bacterial strains. Periodontal disease has been associated with chronic obstructive pulmonary disease (COPD) and we previously found high amounts of Veillonella in the subgingival microflora of COPD subjects. Differentiation of Veillonella is difficult. The aims of this study were to identify subgingival Veillonella isolates by phenotypic, genetic typing and molecular genetic methods, and further, to assess if Veillonella strain properties or identity correlated with periodontal disease or COPD. From 22 subjects, 26 subgingival Veillonella isolates and one pulmonary isolate were analysed. The majority of the subgingival Veillonella isolates were identified as Veillonella parvula. Genotyping showed heterogeneity within strains of the same species. A subgingival and pulmonary isolate in one COPD subject was found to be genetically identical strains of V. parvula. Scanning electron microscopy of the lung biopsy confirmed single small cocci adhering or coaggregating with larger cocci on the airway epithelium. Apart from a variation in cellular fatty acid composition of six subgingival isolates from periodontitis subjects, no correlation between the subgingival Veillonella strains or genotypes and the presence of either periodontitis or COPD was found. In conclusion, V. parvula was the predominant subgingival Veillonella species with high genetic variability within strains of the same species. Subgingival V. parvula can translocate to the lungs; however, Veillonella identity or genotype did not correlate with periodontal disease or COPD. C1 [Leuckfeld, Inga] Natl Hosp Norway, Oslo Univ Hosp, Dept Resp Med, N-0027 Oslo, Norway. [Leuckfeld, Inga; Kristoffersen, Anne K.; Olsen, Ingar] Univ Oslo, Fac Dent, Inst Oral Biol, Oslo, Norway. [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 Leuckfeld, I (reprint author), Natl Hosp Norway, Oslo Univ Hosp, Dept Resp Med, Sognsvannsveien 20, N-0027 Oslo, Norway. EM inga.leuckfeld@rikshospitalet.no FU Faculty of Dentistry, University of Oslo, Oslo, Norway; Departments of Thoracic and Cardiovascular Surgery and Respiratory Medicine, Rikshospitalet Medical Center, Oslo FX This work was supported by the Faculty of Dentistry, University of Oslo, Oslo, Norway, and the Departments of Thoracic and Cardiovascular Surgery and Respiratory Medicine, Rikshospitalet Medical Center, Oslo. We thank Drs. Odd Geiran and circle divide ystein Bj circle divide rtuft for their kind help with the patients and the lung material. Steinar St circle divide len and Dr. Yiqing Cai are thanked for their excellent technical assistance with SEM and TEM respectively, and Emnet Abesha-Belay and Dr. Emenike RK Eribe are acknowledged for their skilful laboratory assistance. Enevold Falsen, CCUG, Gothenburg, Sweden, is acknowledged for his help with long-chain cellular fatty acid analyses. We are grateful to Drs. W.E.C. Moore (deceased) and L.V.H. Moore for gifts from their culture collection. NR 31 TC 4 Z9 4 U1 1 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0903-4641 J9 APMIS JI APMIS PD MAR PY 2010 VL 118 IS 3 BP 230 EP 242 DI 10.1111/j.1600-0463.2009.02584.x PG 13 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 550RX UT WOS:000274147700008 PM 20132189 ER PT J AU Hussein, MRA Al Bshabshe, AA Dalati, T AF Hussein, Mahmoud Rezk A. Al Bshabshe, Ali A. Dalati, Taufik TI Leukemia Cutis: Case Report and Review of Literature SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Review DE leukemia; skin; myeloperoxidase ID SECTIONS AB Leukemias are neoplasms of hematolymphoid cells that predominantly involve the peripheral blood. Cutaneous involvement (leukemia cutis) occurs in chronic myeloid leukemia, chronic lymphocytic leukemia, and in monocytic leukemia. Here, we report a case of a 49-year-old female patient known to have chronic myeloid leukemia presented with multiple cutaneous lesions. The clinicopathologic features were presented and the relevant literature was discussed. C1 [Hussein, Mahmoud Rezk A.; Al Bshabshe, Ali A.; Dalati, Taufik] Asir Cent Hosp, Dept Pathol & Med, Abha, Saudi Arabia. [Hussein, Mahmoud Rezk A.] Univ Wisconsin, Sch Med, Madison, WI USA. [Hussein, Mahmoud Rezk A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Hussein, MRA (reprint author), Assiut Univ, Fac Med, Dept Pathol, Assiut, Egypt. EM mrcpath17@gmail.com NR 5 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-3345 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD MAR PY 2010 VL 18 IS 2 BP 190 EP 191 DI 10.1097/PAI.0b013e3181bfbcdc PG 2 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 563UI UT WOS:000275160000014 PM 19956066 ER PT J AU Gerstner, ER Batchelor, TT AF Gerstner, Elizabeth R. Batchelor, Tracy T. TI Primary Central Nervous System Lymphoma SO ARCHIVES OF NEUROLOGY LA English DT Review ID PRIMARY CNS LYMPHOMA; HIGH-DOSE METHOTREXATE; NON-HODGKINS-LYMPHOMA; PHASE-II; DEFERRED RADIOTHERAPY; EUROPEAN ORGANIZATION; MALIGNANT-LYMPHOMA; FOLLOW-UP; CHEMOTHERAPY; BRAIN AB Primary central nervous system (CNS) lymphoma (PCNSL), an uncommon variant of extranodal non-Hodgkin lymphoma (NHL), can affect any part of the neuraxis including the eyes, brain, leptomeninges, or spinal cord. It accounts for approximately 3% of all the primary CNS tumors diagnosed each year in the United States. Congenital or acquired immunodeficiency is the only established risk factor for PCNSL, and individuals with human immunodeficiency virus (HIV) infection are at greater risk for developing this tumor. Infection with HIV likely accounted for the increased incidence in PCNSL observed from 1970 to 2000, but over the last decade the number of cases of PCNSL has stabilized or decreased to about 0.47 cases per 100 000 persons. Owing to the rarity of PCNSL, the disease has been challenging to study and an effective standard of care has been difficult to establish. Unfortunately, although durable remissions may be achieved for some patients with PCNSL, the tumor relapses in most cases. In this review, we will focus on PCNSL in the immunocompetent host. C1 [Gerstner, Elizabeth R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA 02114 USA. [Gerstner, Elizabeth R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Dept Neurol, Boston, MA 02114 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM egerstner@partners.org NR 28 TC 63 Z9 70 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2010 VL 67 IS 3 BP 291 EP 297 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 565QG UT WOS:000275308600005 PM 20212226 ER PT J AU Walcott, BP Jaglowski, JR Curry, WT AF Walcott, Brian P. Jaglowski, Jeffrey R. Curry, William T., Jr. TI Spinal Epidural Metastasis SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID CORD COMPRESSION C1 [Walcott, Brian P.; Curry, William T., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Jaglowski, Jeffrey R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Walcott, BP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2010 VL 67 IS 3 BP 358 EP 359 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 565QG UT WOS:000275308600016 PM 20212236 ER PT J AU Gupta, SR Agnani, S Tehrani, S Yeh, S Lauer, AK Suhler, EB AF Gupta, Seema R. Agnani, Shivali Tehrani, Shandiz Yeh, Steven Lauer, Andreas K. Suhler, Eric B. TI Endogenous Streptococcus agalactiae (Group B Streptococcus) Endophthalmitis as a Presenting Sign of Precursor T-Cell Lymphoblastic Leukemia SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID BACTERIAL ENDOPHTHALMITIS C1 [Gupta, Seema R.; Agnani, Shivali; Tehrani, Shandiz; Yeh, Steven; Lauer, Andreas K.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Casey Eye Inst, Dept Ophthalmol, Portland, OR 97239 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Suhler, EB (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, Dept Ophthalmol, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM suhlere@ohsu.edu NR 4 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2010 VL 128 IS 3 BP 384 EP 385 PG 3 WC Ophthalmology SC Ophthalmology GA 565QC UT WOS:000275308100023 PM 20212217 ER PT J AU Eversole, GM Moriarty, AT Schwartz, MR Clayton, AC Souers, R Fatheree, LA Chmara, BA Tench, WD Henry, MR Wilbur, DC AF Eversole, Galen M. Moriarty, Ann T. Schwartz, Mary R. Clayton, Amy C. Souers, Rhona Fatheree, Lisa A. Chmara, Beth A. Tench, William D. Henry, Michael R. Wilbur, David C. TI Practices of Participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, 2006 SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ATYPICAL SQUAMOUS-CELLS; CURRENT LABORATORY PRACTICES; UNDETERMINED SIGNIFICANCE; SPECIMEN ADEQUACY; GYNECOLOGIC CYTOLOGY; QUALITY-ASSURANCE; REPORTING RATES; TERMINOLOGY; MANAGEMENT; TESTS AB Context.-Liquid-based preparations (LBPs) and human papillomavirus testing have led to changes in cervical cytology practices. The College of American Pathologists attempts to track practice patterns using a supplemental questionnaire, which allows laboratories to report diagnostic practices. Objective.-To analyze the 2006 reporting practices and to compare the results with the 2003 survey data. Design.-Questionnaire was mailed to 1621 laboratories. Participants included laboratories enrolled in the 2006 College of American Pathologists Gynecologic Proficiency Testing Program or the educational Interlaboratory Comparison Program in Gynecologic Cytology. Results.-Of the 679 responding laboratories (response rate, 42%), most (97.8%; n = 664) had implemented the Bethesda 2001 terminology. The median rate for all preparations with low-grade squamous intraepithelial lesions was 2.5% (2.9% for LBPs) compared with a 2003 median rate of 2.1%; the increase was confined to LBPs. Rates for high-grade squamous intraepithelial lesions (median, 0.5%) and atypical squamous cells have changed little. High-grade squamous intraepithelial lesions and unsatisfactory rates varied at statistically significant levels between types of LBPs. Most atypical squamous cell cases were subclassified as undetermined significance (median, 4.3%). The median ratio of atypical squamous cells to squamous intraepithelial lesions and carcinomas for all specimen types combined was 1.5, similar to the 2003 median ratio of 1.4. The median rates for findings of squamous cell abnormalities for 2006 were significantly higher for LBPs than for conventional smears. Conclusions.-Most responding laboratories have implemented the Bethesda 2001 terminology. There is an increase in LBP low-grade squamous intraepithelial lesion rates when compared with 2003 data. Liquid-based preparations have higher median squamous intraepithelial lesion and atypical squamous cell rates. (Arch Pathol Lab Med. 2010; 134: 331-335) C1 [Eversole, Galen M.] Quest Diagnostics Inc, Dept Pathol, Las Vegas, NV 89119 USA. [Moriarty, Ann T.] AmeriPath Indiana, Dept Pathol, Indianapolis, IN USA. [Schwartz, Mary R.] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. [Clayton, Amy C.; Henry, Michael R.] Mayo Clin, Dept Anat Pathol, Rochester, MN USA. [Souers, Rhona] Coll Amer Pathologists, Dept Biostat, Northfield, IL USA. [Fatheree, Lisa A.; Chmara, Beth A.] Coll Amer Pathologists, Dept Cytol Surveys, Northfield, IL USA. [Tench, William D.] Palomar Med Ctr, Dept Lab Serv, Escondido, CA USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Eversole, GM (reprint author), Quest Diagnostics Inc, Dept Pathol, 4320 Burnham Ave, Las Vegas, NV 89119 USA. EM gmeversole@mac.com FU College of American Pathologists (Northfield, Illinois) FX The College of American Pathologists (Northfield, Illinois) provided support for this study. NR 18 TC 27 Z9 34 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2010 VL 134 IS 3 BP 331 EP 335 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 568NL UT WOS:000275529200002 PM 20196659 ER PT J AU McKenney, JK Amin, MB Epstein, JI Grignon, DJ Oliva, E Reuter, VE Srigley, JR Humphrey, PA AF McKenney, Jesse K. Amin, Mahul B. Epstein, Jonathan I. Grignon, David J. Oliva, Esther Reuter, Victor E. Srigley, John R. Humphrey, Peter A. CA Members Canc Comm Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Carcinoma of the Urethra SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID URINARY-BLADDER; INVASION C1 [Humphrey, Peter A.] Washington Univ, Med Ctr, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Humphrey, Peter A.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [McKenney, Jesse K.] Stanford Univ, Med Ctr, Dept Pathol & Urol, Stanford, CA 94305 USA. [Amin, Mahul B.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Epstein, Jonathan I.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. [Grignon, David J.] Indiana Univ, Dept Pathol, Indianapolis, IN 46204 USA. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Reuter, Victor E.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Srigley, John R.] Credit Valley Hosp, Dept Lab Med, Mississauga, ON, Canada. RP Humphrey, PA (reprint author), Washington Univ, Med Ctr, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave, St Louis, MO 63110 USA. EM humphrey@path.wustl.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2010 VL 134 IS 3 BP 345 EP 350 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 568NL UT WOS:000275529200005 PM 20196662 ER PT J AU Dussel, V Joffe, S Hilden, JM Watterson-Schaeffer, J Weeks, JC Wolfe, J AF Dussel, Veronica Joffe, Steven Hilden, Joanne M. Watterson-Schaeffer, Jan Weeks, Jane C. Wolfe, Joanne TI Considerations About Hastening Death Among Parents of Children Who Die of Cancer SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PHYSICIAN-ASSISTED SUICIDE; PALLIATIVE SEDATION THERAPY; TERMINALLY-ILL PATIENTS; OF-LIFE DECISIONS; ADVANCED DISEASE; END; EUTHANASIA; CARE; ATTITUDES; DESIRE AB Objectives: To estimate the frequency of hastening death discussions, describe current parental endorsement of hastening death and intensive symptom management, and explore whether children's pain influences these views in a sample of parents whose child died of cancer. Design: Cross-sectional survey. Setting: Two tertiary-care US pediatric institutions. Participants: A total of 141 parents of children who died of cancer (response rate, 64%). Outcome Measures: Proportion of parents who (1) considered or (2) discussed hastening death during the child's end of life and who endorsed (3) hastening death or (4) intensive symptom management in vignettes portraying children with end-stage cancer. Results: A total of 19 of 141 (13%; 95% confidence interval [CI], 8%-19%) parents considered requesting hastened death for their child and 9% (95% CI, 4%-14%) discussed hastening death; consideration of hastening death tended to increase with an increase in the child's suffering from pain. In retrospect, 34% (95% CI, 26%42%) of parents reported that they would have considered hastening their child's death had the child been in uncontrollable pain, while 15% or less would consider hastening death for nonphysical suffering. In response to vignettes, 50% (95% CI, 42%-58%) of parents endorsed hastening death while 94% (95% CI, 90%-98%) endorsed intensive pain management. Parents were more likely to endorse hastening death if the vignette involved a child in pain compared with coma (odds ratio, 1.4; 95% CI, 1.1-1.8). Conclusions: More than 10% of parents considered hastening their child's death; this was more likely if the child was in pain. Attention to pain and suffering and education about intensive symptom management may mitigate consideration of hastening death among parents of children with cancer. C1 [Dussel, Veronica; Joffe, Steven; Weeks, Jane C.; Wolfe, Joanne] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dussel, Veronica; Joffe, Steven; Wolfe, Joanne] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Hilden, Joanne M.] Peyton Manning Childrens Hosp St Vincent, Indianapolis, IN USA. [Watterson-Schaeffer, Jan] Childrens Hosp & Clin, St Paul, MN USA. [Weeks, Jane C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. EM joanne_wolfe@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 FU Agency for Health Research and Quality [T32HP10018]; National Cancer Institute [NCI 5 K07 CA096746]; Pine Tree Apple Tennis Classic Oncology Research Fund FX Funding/Support: This study was supported by fellowship T32HP10018 from the Agency for Health Research and Quality (Dr Dussel); and grant NCI 5 K07 CA096746 from the National Cancer Institute (Dr Wolfe); and partially supported by the Pine Tree Apple Tennis Classic Oncology Research Fund (Ms Watterson-Schaeffer). NR 41 TC 8 Z9 8 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 2010 VL 164 IS 3 BP 231 EP 237 PG 7 WC Pediatrics SC Pediatrics GA 562IA UT WOS:000275042300004 PM 20194255 ER PT J AU Joffe, S AF Joffe, Steven TI Framing the Benefits of Cancer Clinical Trials SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material ID PARTICIPATION; US C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM steven_joffe@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 NR 15 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 2010 VL 164 IS 3 BP 293 EP 294 PG 2 WC Pediatrics SC Pediatrics GA 562IA UT WOS:000275042300015 PM 20194266 ER PT J AU Chen, SL Bih, LI Chen, GD Huang, YH You, YH Lew, HL AF Chen, Sung-Lang Bih, Liu-Ing Chen, Gin-Den Huang, Yu-Hui You, Ya-Hui Lew, Henry L. TI Transrectal Ultrasound-Guided Transperineal Botulinum Toxin A Injection to the External Urethral Sphincter for Treatment of Detrusor External Sphincter Dyssynergia in Patients With Spinal Cord Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Autonomic dysreflexia; Botulinum toxins; Rehabilitation; Ultrasonography; Urinary bladder; Urodynamics ID FOLLOW-UP; DYSFUNCTION; DISEASE; MUSCLE; MEN AB Chen S-L, Bih L-T, Chen G-I), Huang Y-H, You Y-H, Lew HL. Transrectal ultrasound guided transperineal botulinum toxin A injection to the external urethral sphincter for treatment of detrusor external sphincter dyssynergia in patients with spinal cord injury. Arch Phys Med Rehabil 2010;91:340-4. Objective: To evaluate the effects of a single transrectal ultrasound (TRUS)-guided transperineal injection of botulinum toxin A (BTX-A) to the external urethral sphincter (EUS) for treating detrusor external sphincter dyssynergia (DESD). Design: Descriptive study. Setting: Rehabilitation hospital affiliated with a medical university. Participants: Patients (N=18) with suprasacral spinal cord injury who had DESD confirmed on video-urodynamic study. Interventions: A single dose of 100U BTX-A was applied into the EUS via TRUS-guided transperineal route injection. Main Outcome Measures: Maximal detrusor pressure, detrusor leak-point pressure, integrated electromyography (iEMG), maximal pressure on static urethral pressure profilometry, and postvoiding residuals. Results: There were significant reductions in iEMG (P=.008) and static (P=.012) and dynamic urethral pressure (P=.023), but not in detrusor pressure and detrusor leak-point pressure after treatment. Postvoiding residuals also significantly decreased in the first and second month after treatment (P<.012). Conclusions: TRUS-guided transperineal injection of BTX-A has beneficial effects in treating DESD. C1 [Bih, Liu-Ing; Huang, Yu-Hui] Chung Shan Med Univ, Dept Phys Med & Rehabil, Chung Shan Med Univ Hosp, Sch Med, Taichung 406, Taiwan. [Chen, Sung-Lang] Chung Shan Med Univ, Dept Urol, Chung Shan Med Univ Hosp, Sch Med, Taichung 406, Taiwan. [Chen, Gin-Den] Chung Shan Med Univ, Dept Obstet & Gynecol, Chung Shan Med Univ Hosp, Sch Med, Taichung 406, Taiwan. [You, Ya-Hui] Taipei City Hosp, Dept Nursing, Zhongxiao Branch, Taipei, Taiwan. [Lew, Henry L.] VA Boston Healthcare Syst, Phys Med & Rehabil Serv, Boston, MA USA. RP Huang, YH (reprint author), Chung Shan Med Univ, Dept Phys Med & Rehabil, 1142 Sect 3,Tay Yuan Rd, Taichung 406, Taiwan. EM yhhuang59@hotmail.com FU National Science Council of the Republic of China [NSC 972314B040003] FX Supported by the National Science Council of the Republic of China (grant no. NSC NSC 972314B040003). NR 34 TC 8 Z9 11 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2010 VL 91 IS 3 BP 340 EP 344 DI 10.1016/j.apmr.2009.11.006 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 592YM UT WOS:000277417900002 PM 20298821 ER PT J AU Hula, WD Doyle, PJ Hula, SNA AF Hula, William D. Doyle, Patrick J. Hula, Shannon N. Austermann TI Patient-Reported Cognitive and Communicative Functioning: 1 Construct or 2? SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Communication disorders; Patient outcomes assessment; Rehabilitation; Stroke ID FIT STATISTICS; ITEM BANKS; SCALE; STROKE; RELIABILITY; VALIDITY; OUTCOMES; SCORE; UNIDIMENSIONALITY; DIMENSIONALITY AB Hula WD, Doyle PJ, Austermann Hula SN. Patient-reported cognitive and communicative functioning: 1 construct or 2? Arch Phys Med Rehabil 2010;91:400-6. Objectives: To examine the dimensionality of scales for measuring patient-reported cognitive and communicative functioning in a sample of stroke survivors and to evaluate the consequences for measurement of treating them as a single, undifferentiated construct. Design: Secondary analysis of existing cross-sectional data. Setting: Data were collected in outpatient rehabilitation clinics and in the community. Participants: Unilateral stroke survivors (N=316) 3 months or more postonset referred for participation in research. Interventions: Not applicable. Main Outcome Measures: The Burden of Stroke Scale cognition and communication domain scales were evaluated by using confirmatory factor analysis. Rasch analysis, and tests of differential item functioning (DIF). To evaluate the impact of multidimensionality on the measurement of individual patients, separately estimated cognition and communication scores were compared. Combined and separately estimated scores were also examined for responsiveness to group differences in the presence of cognitive and communicative impairment. Results: Factor analysis and Rasch model fit analyses equivocally supported the unidimensionality of the item pool. DIF analyses between participants with right versus left hemisphere stroke suggested multidimensionality. Scaling cognition and communication items separately resulted in different person scores for a significant number of patients and greater responsiveness to group differences. Conclusions: Patient-reported scales assessing communication along with more general cognitive activities may possess an internal structure that is inconsistent with a unidimensional measurement model with potential negative consequences for measurement. C1 [Hula, William D.; Doyle, Patrick J.; Hula, Shannon N. Austermann] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15206 USA. [Hula, William D.; Doyle, Patrick J.] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. RP Hula, WD (reprint author), VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, 7180 Highland Dr,132A-H, Pittsburgh, PA 15206 USA. EM William.Hula@va.gov FU Veterans Affairs Rehabilitation Research and Development (VA RRD); Veterans Affairs Rehabilitation Research and Development [C2386R]; [C6210M] FX Supported by the Veterans Affairs Rehabilitation Research and Development (VA RR&D) Career Development Award (grant no. C6210M) and the Veterans Affairs Rehabilitation Research and Development Merit Review Award (grant no. C2386R). NR 41 TC 3 Z9 3 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2010 VL 91 IS 3 BP 400 EP 406 DI 10.1016/j.apmr.2009.11.013 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 592YM UT WOS:000277417900012 PM 20298831 ER PT J AU Monach, PA Nigrovic, PA Chen, M Hock, H Lee, DM Benoist, C Mathis, D AF Monach, Paul A. Nigrovic, Peter A. Chen, Mei Hock, Hanno Lee, David M. Benoist, Christophe Mathis, Diane TI Neutrophils in a Mouse Model of Autoantibody-Mediated Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; ANTIBODY-INDUCED ARTHRITIS; TUMOR-NECROSIS-FACTOR; II COLLAGEN ANTIBODY; TRANSCRIPTION FACTOR GFI-1; INFL AMMATORY ARTHRITIS; RECEPTOR GAMMA-CHAIN; MAST-CELLS; INFLAMMATORY ARTHRITIS; RHEUMATOID-ARTHRITIS AB Objective. Neutrophils represent a prominent component of inflammatory joint effusions and are required for synovial inflammation in mouse models, but the mechanisms are poorly understood. In this study, we developed a system with which to test the importance of the production of specific factors by neutrophils in a mouse model of arthritis. Methods. Neutrophil-deficient Gfi-1(-/-) mice were administered sublethal doses of radiation and were then engrafted with donor bone marrow cells (BMCs), which resulted in the production of mature neutrophils within 2 weeks. By reconstituting with BMCs from mice lacking selected proinflammatory factors, we generated mice that specifically lacked these factors on their neutrophils. Arthritis was initiated by transfer of K/BxN serum to identify the role of defined neutrophil factors on the incidence and severity of arthritis. Results. Neutrophils lacking the signaling chain of stimulatory Fc receptors (FcR gamma(-/-)) were unable to elicit arthritis, but neutrophils lacking Fc gamma RIII still did so. Neutrophils lacking the chemotactic or adhesion receptor C5a receptor (C5aR) or CD11a/lymphocyte function-associated antigen 1 (LFA-1) also failed to initiate arthritis but could enter joints in which inflammation had been initiated by wild-type neutrophils. Neutrophils unable to produce interleukin-1 alpha (IL-1 alpha) and IL-1 beta (IL-1 alpha/beta(-/-)) or leukotrienes (5-lipoxygenase [5-LOX(-/-)]) produced arthritis of intermediate severity. The inability of neutrophils to make tumor necrosis factor or to express receptors for tumor necrosis factor or IL-1 had no effect on arthritis. Conclusion. A novel transfer system was developed to identify neutrophil production of FcR gamma, C5aR, and CD11a/LFA-1 as critical components of autoantibody-mediated arthritis. Neutrophil production of IL-1 and leukotriene B(4) likely contributes to inflammation but is not essential. Molecular requirements for neutrophil influx into joints become more permissive after inflammation is initiated. C1 [Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Monach, Paul A.; Benoist, Christophe; Mathis, Diane] Brigham & Womens Hosp, Joslin Diabet Ctr, Boston, MA 02115 USA. [Nigrovic, Peter A.; Chen, Mei; Lee, David M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Hock, Hanno] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur,NRB 1052, Boston, MA 02115 USA. EM cb@hms.harvard.edu; dm@hms.harvard.edu FU NIH [R01-AR-46580, R01-AR-055271, P01-AI-65858]; National Institute of Diabetes and Digestive and Kidney Diseases; Arthritis Foundation; Young Chair; Abbott Scholar award for Rheumatology Research FX Supported by the NIH (grants R01-AR-46580, R01-AR-055271, and P01-AI-65858) and by the Diabetes and Endocrinology Research Center at Joslin Diabetes Center, which is funded by a core facilities grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Monach's work was supported by an Abbott Scholar award for Rheumatology Research and by an Arthritis Investigator award from the Arthritis Foundation. Drs. Benoist and Mathis's work was supported by funding through the Young Chair. NR 65 TC 52 Z9 53 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAR PY 2010 VL 62 IS 3 BP 753 EP 764 DI 10.1002/art.27238 PG 12 WC Rheumatology SC Rheumatology GA 619LR UT WOS:000279432200015 PM 20191628 ER PT J AU Stone, JH Khosroshahi, A Deshpande, V Stone, JR AF Stone, John H. Khosroshahi, Arezou Deshpande, Vikram Stone, James R. TI IgG4-Related Systemic Disease Accounts for a Significant Proportion of Thoracic Lymphoplasmacytic Aortitis Cases SO ARTHRITIS CARE & RESEARCH LA English DT Article ID TERM-FOLLOW-UP; AUTOIMMUNE PANCREATITIS; SCLEROSING DISEASE; ANEURYSM; PERIAORTITIS; CLASSIFICATION; REGURGITATION; DISSECTION; PATHOLOGY; ARTERITIS AB Objective. IgG4-related systemic disease, a disorder recognized only recently, can cause lymphoplasmacytic inflammation in the thoracic aorta. The percentage of cases caused by IgG4-related systemic disease is not known. We aimed to determine the percentage of noninfectious thoracic aortitis cases that are associated with IgG4-related systemic disease and to establish pathologic criteria for identifying involvement of the thoracic aorta by this disorder. Methods. We searched our Pathology Service database to identify patients with noninfectious thoracic aortitis who underwent resection over a 5-year time span. The histologic features of these cases were reviewed. All cases of lymphoplasmacytic aortitis and representative cases of giant cell aortitis and atherosclerosis were stained by immunohistochemistry for IgG4 and for the plasma cell marker CD138. We determined the fraction of plasma cells that stained for IgG4. Results. Of 638 resected thoracic aortas, 33 (5.2%) contained noninfectious aortitis. Four of these cases (12% of all patients with noninfectious aortitis) had histologic features of lymphoplasmacytic aortitis. Three of those 4 cases (9% of the noninfectious aortitis cases) demonstrated pathologic involvement by IgG4-related systemic disease, with an elevated proportion of plasma cells staining for IgG4 (mean +/- SD 0.82 +/- 0.08) compared with cases of giant cell aortitis (0.18 +/- 0.13) and atherosclerosis (0.19 +/- 0.08; P < 0.00001). Conclusion. IgG4-related systemic disease accounted for 75% of lymphoplasmacytic aortitis cases and 9% of all cases of noninfectious thoracic aortitis in our institution during a 5-year period. Immunohistochemical assessment of the percentage of plasma cells that stained for IgG4 in resected aortas was helpful in identifying patients with IgG4-related systemic disease. C1 [Stone, James R.] Massachusetts Gen Hosp, Simches Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, 185 Cambridge St,CPZN 8400, Boston, MA 02114 USA. EM jrstone@partners.org NR 39 TC 71 Z9 78 U1 0 U2 5 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 MAR PY 2010 VL 62 IS 3 BP 316 EP 322 DI 10.1002/acr.20095 PG 7 WC Rheumatology SC Rheumatology GA 639MP UT WOS:000280979200005 PM 20391477 ER PT J AU Emkey, GR Stone, JH AF Emkey, Gregory R. Stone, John H. TI A 46-Year-Old Woman With Chin Pain and a Fainting Spell SO ARTHRITIS CARE & RESEARCH LA English DT Article ID LYME-DISEASE; NUMB CHIN; TEMPORAL ARTERITIS; CELL ARTERITIS; CARDITIS C1 [Emkey, Gregory R.; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Emkey, GR (reprint author), Massachusetts Gen Hosp, Bulfinch Bldg,Room 165,55 Fruit St, Boston, MA 02114 USA. EM gemkey@partners.org NR 23 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD MAR PY 2010 VL 62 IS 3 BP 434 EP 438 DI 10.1002/acr.20093 PG 5 WC Rheumatology SC Rheumatology GA 639MP UT WOS:000280979200020 PM 20391493 ER PT J AU Hodi, FS AF Hodi, F. Stephen TI Overcoming immunological tolerance to melanoma: Targeting CTLA-4 SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Review DE antibodies; combination therapy; CTLA-4; immunotherapy; melanoma ID CYTOTOXIC-T-LYMPHOCYTE; TUMOR-INFILTRATING LYMPHOCYTES; ANTIGEN-4 MONOCLONAL-ANTIBODY; PHASE-I TRIAL; METASTATIC MELANOMA; IMMUNE-RESPONSE; BLOCKADE; AUTOIMMUNITY; CANCER; IMMUNOTHERAPY AB The use of immunotherapeutics in melanoma has received much attention, and recent advances to further characterize the regulatory components of the immune system and the importance of co-stimulatory molecules have opened a new area for clinical investigation. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) serves as a negative regulator of immunity. Recent trials administering fully human anti-CTLA-4 monoclonal antibodies to melanoma patients have demonstrated clinically meaningful responses. Treatment with CTLA-4 blocking antibodies, however, is not without potential toxicities. Autoimmune side-effects, the most common being colitis-associated diarrhea, are frequently associated with clinical responses. In efforts to build upon prior vaccination efforts as well as attempt to offer patients clinically meaningful immune responses with a CTLA-4 blockade but without significant toxicities, we conducted a clinical trial in patients who previously received autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GVAX; Cell Genesys, South San Francisco, CA, USA) with periodic infusions of CTLA-4 blocking antibodies. This sequential treatment resulted in clinically significant anti-tumor immunity without grade 3 or 4 toxicity in most patients. Pathological analyses following treatment of pre-existing tumors revealed a linear correlation between tumor necrosis and the ratio of intra-tumoral CD8+ effector cells to FoxP3+ regulatory cells (T(regs)). Effective anti-tumor immunity and serious autoimmunity can be disassociated. Further targeting of anti-tumor T(regs)in combinatorial therapy approaches may be a rich avenue of future investigation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM stephen_hodi@dfci.harvard.edu NR 38 TC 12 Z9 12 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-7555 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD MAR PY 2010 VL 6 SU 1 BP S16 EP S26 DI 10.1111/j.1743-7563.2010.01271.x PG 11 WC Oncology SC Oncology GA 563MO UT WOS:000275136800003 PM 20482528 ER PT J AU Betjemann, RS Johnson, EP Barnard, H Boada, R Filley, CM Filipek, PA Willcutt, EG DeFries, JC Pennington, BF AF Betjemann, Rebecca S. Johnson, Erin Phinney Barnard, Holly Boada, Richard Filley, Christopher M. Filipek, Pauline A. Willcutt, Erik G. DeFries, John C. Pennington, Bruce F. TI Genetic Covariation Between Brain Volumes and IQ, Reading Performance, and Processing Speed SO BEHAVIOR GENETICS LA English DT Article DE Twin design; MRI; Brain volume; Intelligence; Processing speed; Reading ID ENVIRONMENTAL-INFLUENCES; WORKING-MEMORY; PHONOLOGICAL AWARENESS; INSPECTION TIME; HUMAN NEOCORTEX; WHITE-MATTER; INTELLIGENCE; VARIABILITY; DISABILITY; MRI AB Although there has been much interest in the relation between brain size and cognition, few studies have investigated this relation within a genetic framework and fewer still in non-adult samples. We analyzed the genetic and environmental covariance between structural MRI data from four brain regions (total brain volume, neocortex, white matter, and prefrontal cortex), and four cognitive measures (verbal IQ (VIQ), performance IQ (PIQ), reading ability, and processing speed), in a sample of 41 MZ twin pairs and 30 same-sex DZ twin pairs (mean age at cognitive test = 11.4 years; mean age at scan = 15.4 years). Multivariate Cholesky decompositions were performed with each brain volume measure entered first, followed by the four cognitive measures. Consistent with previous research, each brain and cognitive measure was found to be significantly heritable. The novel finding was the significant genetic but not environmental covariance between brain volumes and cognitive measures. Specifically, PIQ shared significant common genetic variance with all four measures of brain volume (r (g) = .58-.82). In contrast, VIQ shared significant genetic influence with neocortex volume only (r (g) = .58). Processing speed was significant with total brain volume (r (g) = .79), neocortex (r (g) = .64), and white matter (r (g) = .89), but not prefrontal cortex. The only brain measure to share genetic influence with reading was total brain volume (r (g) = .32), which also shared genetic influences with processing speed. C1 [Betjemann, Rebecca S.] Regis Univ, Dept Psychol, Denver, CO 80221 USA. [Johnson, Erin Phinney; Barnard, Holly; Boada, Richard; Pennington, Bruce F.] Univ Denver, Denver, CO USA. [Boada, Richard; Filley, Christopher M.] Univ Colorado, Denver Sch Med, Denver, CO 80202 USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Filipek, Pauline A.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Willcutt, Erik G.; DeFries, John C.] Univ Colorado, Boulder, CO 80309 USA. RP Betjemann, RS (reprint author), Regis Univ, Dept Psychol, D-12,3333 Regis Blvd, Denver, CO 80221 USA. EM rbetjema@regis.edu FU NIMH [T32 MH016880-25]; NIH [HD027802] FX Initial work on this paper was done when R. Betjemann was a postdoctoral trainee at the Institute for Behavioral Genetics, University of Colorado, Boulder, CO. This training was funded by NIMH training grant T32 MH016880-25. This project was also funded by NIH grant HD027802 to the Colorado Learning Disabilities Research Center, of which B. Pennington, J. DeFries, and E. Willcutt are Co-PIs. NR 61 TC 14 Z9 14 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD MAR PY 2010 VL 40 IS 2 SI SI BP 135 EP 145 DI 10.1007/s10519-009-9328-2 PG 11 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 561GM UT WOS:000274964000004 PM 20072853 ER PT J AU Saleh, FM Malin, HM Grudzinskas, AJ Vitacco, MJ AF Saleh, Fabian M. Malin, H. Martin Grudzinskas, Albert J., Jr. Vitacco, Michael J. TI Paraphilias with Co-Morbid Psychopathy: The Clinical and Legal Significance to Sex Offender Assessments SO BEHAVIORAL SCIENCES & THE LAW LA English DT Article ID PREDATOR CIVIL COMMITMENT; DIAGNOSTIC RELIABILITY; CHECKLIST; CONSTRUCT; AROUSAL; SADISM AB This article briefly discusses the historical development of the constructs of paraphilia and psychopathy. An overview of recent developments in the assessment of these constructs for legal purposes is also provided. The historical, clinical, legal, and ethical obligations of clinicians who work with persons suffering from paraphilias and comorbid psychopathy is then reviewed. An emphasis of the current article is integrating recent developments in the construct of psychopathy into a discussion of sex offender risk assessment and treatment. The co-morbidity of psychopathy and paraphilias as factors in predicting risk of recidivism is reviewed. The need for practitioners to remain cognizant of language requirements in both legal and clinical contexts is addressed. Finally, this article reviews the legal history of sex offender legislation and its evolution into current United States Supreme Court jurisprudence. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Saleh, Fabian M.] Harvard Univ, Sch Med, Law & Psychiat Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Malin, H. Martin] Inst Adv Study Human Sexual, San Francisco, CA USA. [Malin, H. Martin] Natl Inst Study Prevent & Treatment Sexual Trauma, Baltimore, MD USA. [Grudzinskas, Albert J., Jr.] Univ Massachusetts, Sch Med, Dept Psychiat, Coordinator Legal Studies, Worcester, MA 01655 USA. [Vitacco, Michael J.] Mendota Mental Hlth Inst, Madison, WI USA. RP Saleh, FM (reprint author), Harvard Univ, Sch Med, Law & Psychiat Serv, Massachusetts Gen Hosp, WACC 812,15 Parkman St, Boston, MA 02114 USA. EM fsaleh@partners.org NR 53 TC 5 Z9 5 U1 2 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0735-3936 J9 BEHAV SCI LAW JI Behav. Sci. Law PD MAR-APR PY 2010 VL 28 IS 2 BP 211 EP 223 DI 10.1002/bsl.933 PG 13 WC Psychology, Applied; Law SC Psychology; Government & Law GA 597FU UT WOS:000277742700006 PM 20422646 ER PT J AU Beck, JC AF Beck, James C. TI Dangerous Severe Personality Disorder: The Controversy Continues SO BEHAVIORAL SCIENCES & THE LAW LA English DT Article ID MENTAL-HEALTH; PUBLIC PROTECTION; PSYCHIATRY; PROPOSALS; PEOPLE; ACT AB Following a high profile murder in 1996, the government in England moved to involuntarily contain individuals, almost all men, who were thought to be at risk of violence and to have a personality disorder. In 2008 the Dangerous Severe Personality Disorder program of assessment, commitment and treatment for this newly defined legal category of persons went into effect. The program was initially opposed by a majority of the forensic psychiatrists in England, but consistently supported by a minority. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Beck, James C.] Harvard Univ, Sch Med, Cambridge, MA 02140 USA. [Beck, James C.] Massachusetts Gen Hosp, Law & Psychiat Serv, Cambridge, MA 02140 USA. RP Beck, JC (reprint author), Harvard Univ, Sch Med, 34 Bates St, Cambridge, MA 02140 USA. EM jamesbeck56@gmail.com NR 17 TC 3 Z9 3 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0735-3936 J9 BEHAV SCI LAW JI Behav. Sci. Law PD MAR-APR PY 2010 VL 28 IS 2 BP 277 EP 288 DI 10.1002/bsl.931 PG 12 WC Psychology, Applied; Law SC Psychology; Government & Law GA 597FU UT WOS:000277742700010 PM 20422650 ER PT J AU Fabbro, D Manley, PW Jahnke, W Liebetanz, J Szyttenholm, A Fendrich, G Strauss, A Zhang, JM Gray, NS Adrian, F Warmuth, M Pelle, X Grotzfeld, R Berst, F Marzinzik, A Cowan-Jacob, SW Furet, P Mestan, J AF Fabbro, Doriano Manley, Paul W. Jahnke, Wolfgang Liebetanz, Janis Szyttenholm, Alexandra Fendrich, Gabriele Strauss, Andre Zhang, Jianming Gray, Nathanael S. Adrian, Francisco Warmuth, Markus Pelle, Xavier Grotzfeld, Robert Berst, Frederic Marzinzik, Andreas Cowan-Jacob, Sandra W. Furet, Pascal Mestan, Juergen TI Inhibitors of the Abl kinase directed at either the ATP- or myristate-binding site SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article; Proceedings Paper CT 6th International Conference on Inhibitors of Protein Kinases ( IPK 2009) CY JUN 27-JUL 01, 2009 CL Warsaw, POLAND DE Abl; Imatinib resistance; Myristate binders; Kinase inhibitors; Abl structure ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL; PROTEIN-KINASES; C-ABL; STRUCTURAL BIOLOGY; TYROSINE KINASES; RESISTANCE; IMATINIB; MUTATION AB The ATP-competitive inhibitors dasatinib and nilotinib, which bind to catalytically different conformations of the Abl kinase domain, have recently been approved for the treatment of imatinib-resistant CML These two new drugs, albeit very efficient against most of the imatinib-resistant mutants of Bcr-Abl, fail to effectively suppress the Bcr-Abl activity of the T3151 (or gatekeeper) mutation. Generating new ATP site-binding drugs that target the T3151 in Abl has been hampered, amongst others, by target selectivity, which is frequently an issue when developing ATP-competitive inhibitors. Recently, using an unbiased cellular screening approach, GNF-2, a non-ATP-competitive inhibitor, has been identified that demonstrates cellular activity against Bcr-Abl transformed cells. The exquisite selectivity of GNF-2 is due to the finding that it targets the myristate binding site located near the C-terminus of the Abl kinase domain, as demonstrated by genetic approaches, solution NMR and X-ray crystallography. GNF-2, like myristate, is able to induce and/or stabilize the clamped inactive conformation of AN analogous to the SH2-Y527 interaction of Src. The molecular mechanism for allosteric inhibition by the GNF-2 inhibitor class, and the combined effects with ATP-competitive inhibitors such as nilotinib and imatinib on wild-type Abl and imatinib-resistant mutants, in particular the T3151 gatekeeper mutant, are reviewed. (C) 2010 Elsevier B.V. All rights reserved. C1 [Fabbro, Doriano; Manley, Paul W.; Jahnke, Wolfgang; Liebetanz, Janis; Szyttenholm, Alexandra; Fendrich, Gabriele; Strauss, Andre; Warmuth, Markus; Pelle, Xavier; Grotzfeld, Robert; Berst, Frederic; Marzinzik, Andreas; Cowan-Jacob, Sandra W.; Furet, Pascal; Mestan, Juergen] Novartis Inst BioMed Res, CH-4002 Basel, Switzerland. [Adrian, Francisco] GNF, La Jolla, CA USA. [Zhang, Jianming; Gray, Nathanael S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fabbro, D (reprint author), Novartis Inst BioMed Res, CH-4002 Basel, Switzerland. EM doriano.fabbro@novartis.com NR 46 TC 30 Z9 30 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD MAR PY 2010 VL 1804 IS 3 SI SI BP 454 EP 462 DI 10.1016/j.bbapap.2009.12.009 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 559ZX UT WOS:000274872500006 PM 20152788 ER PT J AU Eck, MJ Yun, CH AF Eck, Michael J. Yun, Cai-Hong TI Structural and mechanistic underpinnings of the differential drug sensitivity of EGFR mutations in non-small cell lung cancer SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article; Proceedings Paper CT 6th International Conference on Inhibitors of Protein Kinases ( IPK 2009) CY JUN 27-JUL 01, 2009 CL Warsaw, POLAND DE Tyrosine kinase; Epidermal growth factor receptor; X-ray crystallography; Gefitinib; Lung cancer; Drug resistance ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITORS; CHRONIC MYELOID-LEUKEMIA; ACQUIRED-RESISTANCE; CLINICAL-RESPONSE; BCR-ABL; GEFITINIB; MUTANTS; DOMAIN; ACTIVATION AB EGFR and other ErbB-family tyrosine kinases are overexpressed in many human tumors, and their aberrant expression and mutational activation is associated with the development, progression and aggressiveness of a number of malignancies. Thus the EGFR kinase has long been recognized as a potential drug target in oncology, and small-molecule inhibitors have been under development for more than two decades. As a result of their effectiveness in treating non-small cell lung cancers (NSCLCs) driven by somatic mutations in the EGFR kinase, gefitinib and erlotinib were the first EGFR tyrosine kinase inhibitors (TKIs) approved for clinical use. Ironically, these drugs found their target against mutant forms of the EGFR kinase, which have altered enzyme active sites, and not against the wild type (WT) kinase against which their potency and selectivity was carefully honed. Here we review recent structural and enzymological studies that explore the exquisite sensitivity of a subset of these lung cancer mutants to gefitinib and erlotinib. We discuss available structural evidence for the mechanisms of activation of the EGFR kinase by these mutants, and compare it to physiologic activation of the kinase by ligand-induced dimerization. Finally, we consider the mechanisms by which the secondary T790M "gatekeeper" mutation confers resistance to gefitinib and erlotinib. (C) 2009 Elsevier B.V. All rights reserved. C1 [Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 44 Binney St, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu FU NCI NIH HHS [R01 CA080942, R01 CA116020-05, R01 CA080942-08, R01 CA080942-06A1, R01 CA116020, R01 CA080942-10, R01 CA080942-09, R01 CA116020-04, R01 CA080942-07, R01 CA116020-01A1, R01 CA116020-03, R01 CA116020-02]; NHLBI NIH HHS [P01 HL048675-170012, P01 HL048675-150012, P01 HL048675-160012, P01 HL048675-140012, P01 HL048675-130012, P01 HL048675] NR 40 TC 52 Z9 55 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 EI 0006-3002 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD MAR PY 2010 VL 1804 IS 3 SI SI BP 559 EP 566 DI 10.1016/j.bbapap.2009.12.010 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 559ZX UT WOS:000274872500019 PM 20026433 ER PT J AU Shoemaker, LD Arlotta, P AF Shoemaker, Lorelei D. Arlotta, Paola TI Untangling the cortex: Advances in understanding specification and differentiation of corticospinal motor neurons SO BIOESSAYS LA English DT Review DE Bhlhb5; Clim1; corticospinal motor neurons (CSMN); Crim1; Ctip2; Diap3; FACS; Fezf2; Mu-Crystallin; Satb2; Sox5; subcerebral projection neurons ID DEVELOPING CEREBRAL-CORTEX; TRANSLATIONAL PROFILING APPROACH; SUBCORTICAL PROJECTION NEURONS; SUBTYPE-SPECIFIC GENES; SPINAL-CORD-INJURY; PAX6 MUTANT MICE; CNS CELL-TYPES; MAMMALIAN TELENCEPHALON; INTERNEURON DIVERSITY; CORTICAL INTERNEURONS AB The mature cerebral cortex contains a staggering variety of projection neuron subtypes, and a number of complementary studies have recently begun to define their identity and embryonic origin. Among the different types of cortical projection neurons, subcerebral projection neurons, including corticospinal motor neurons (CSMN), have been extensively studied and some of the molecular controls over their differentiation have been elucidated. Here, we first provide an overview of the approaches used to purify and molecularly profile neuronal populations of the neocortex and, more broadly, of the central nervous system (CNS). Next, we specifically review recent progress in understanding the genes that define and control development of the CSMN population. Finally, we briefly discuss the relevance of this work to current questions regarding the mechanisms of the establishment of projection neuron subtype identity in the neocortex and its implications to direct the differentiation of CSMN for therapeutic benefit. C1 [Shoemaker, Lorelei D.; Arlotta, Paola] Harvard Univ, Ctr Regenerat Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Shoemaker, Lorelei D.; Arlotta, Paola] Harvard Univ, Dept Neurosurg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Arlotta, Paola] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. [Arlotta, Paola] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Arlotta, P (reprint author), Harvard Univ, Ctr Regenerat Med, Massachusetts Gen Hosp, Sch Med, Simches Res Bldg,Room 4238,185 Cambridge St, Boston, MA 02114 USA. EM paola_arlotta@hms.harvard.edu FU NIH [NS062849]; Harvard Stem Cell Institute; Spastic Paraplegia Foundation; William Randolph Hearst Fellowship FX We would like to thank Zachary Trayes-Gibson, Simona Lodato, Caroline Rouaux, and Eiman Azim for their Suggestions and critical reading. This work was partially supported by the NIH (NS062849), the Harvard Stem Cell Institute and the Spastic Paraplegia Foundation to P A.; L. D. S. was partially supported by a William Randolph Hearst Fellowship. NR 105 TC 15 Z9 15 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD MAR PY 2010 VL 32 IS 3 BP 197 EP 206 DI 10.1002/bies.200900114 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 568FY UT WOS:000275508900003 PM 20108227 ER PT J AU Rimol, LM Panizzon, MS Fennema-Notestine, C Eyler, LT Fischl, B Franz, CE Hagler, DJ Lyons, MJ Neale, MC Pacheco, J Perry, ME Schmitt, JE Grant, MD Seidman, LJ Thermenos, HW Tsuang, MT Eisen, SA Kremen, WS Dale, AM AF Rimol, Lars M. Panizzon, Matthew S. Fennema-Notestine, Christine Eyler, Lisa T. Fischl, Bruce Franz, Carol E. Hagler, Donald J. Lyons, Michael J. Neale, Michael C. Pacheco, Jennifer Perry, Michele E. Schmitt, J. Eric Grant, Michael D. Seidman, Larry J. Thermenos, Heidi W. Tsuang, Ming T. Eisen, Seth A. Kremen, William S. Dale, Anders M. TI Cortical Thickness Is Influenced by Regionally Specific Genetic Factors SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Cortical thickness; endophenotypes; genetic correlation; heritability; imaging genetics; MRI; twins ID POSTTRAUMATIC-STRESS-DISORDER; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; HUMAN BRAIN STRUCTURE; COORDINATE SYSTEM; MRI; TWIN; RELIABILITY; RECONSTRUCTION; SEGMENTATION AB Background: Although global brain structure is highly heritable, there is still variability in the magnitude of genetic influences on the size of specific regions. Yet, little is known about the patterning of those genetic influences, i.e., whether the same genes influence structure throughout the brain or whether there are regionally specific sets of genes. Methods: We mapped the heritability of cortical thickness throughout the brain using three-dimensional structural magnetic resonance imaging in 404 middle-aged male twins. To assess the amount of genetic overlap between regions, we then mapped genetic correlations between three selected seed points and all other points comprising the continuous cortical surface. Results: There was considerable regional variability in the magnitude of genetic influences on cortical thickness. The primary visual (V1) seed point had strong genetic correlations with posterior sensory and motor areas. The anterior temporal seed point had strong genetic correlations with anterior frontal regions but not with V1. The middle frontal seed point had strong genetic correlations with inferior parietal regions. Conclusions: These results provide strong evidence of regionally specific patterns rather than a single, global genetic factor. The patterns are largely consistent with a division between primary and association cortex, as well as broadly defined patterns of brain gene expression, neuroanatomical connectivity, and brain maturation trajectories, but no single explanation appears to be sufficient. The patterns do not conform to traditionally defined brain structure boundaries. This approach can serve as a step toward identifying novel phenotypes for genetic association studies of psychiatric disorders and normal and pathological cognitive aging. C1 [Panizzon, Matthew S.; Fennema-Notestine, Christine; Eyler, Lisa T.; Franz, Carol E.; Perry, Michele E.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Rimol, Lars M.; Fennema-Notestine, Christine; Hagler, Donald J.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Rimol, Lars M.] Ulleval Univ, Div Psychiat, Oslo, Norway. Univ Oslo, Inst Psychiat, Oslo, Norway. [Eyler, Lisa T.; Tsuang, Ming T.; Kremen, William S.] Vet Affairs San Diego Healthcare Syst, La Jolla, CA USA. [Fischl, Bruce; Pacheco, Jennifer] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lyons, Michael J.; Grant, Michael D.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Neale, Michael C.; Schmitt, J. Eric] Virginia Commonwealth Univ, Dept Psychiat & Human Genet, Richmond, VA USA. [Perry, Michele E.] Univ Calif San Diego, Dept Cognit Neurosci, La Jolla, CA 92093 USA. [Seidman, Larry J.; Thermenos, Heidi W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Eisen, Seth A.] Dept Vet Affairs, Washington, DC USA. [Eisen, Seth A.] Washington Univ, Dept Med, St Louis, MO USA. [Eisen, Seth A.] Washington Univ, Dept Psychiat, St Louis, MO USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Kremen, WS (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,Mail Code 0738, La Jolla, CA 92093 USA. EM wkremen@ucsd.edu RI Lyons, Michael/B-6119-2011; OI Lyons, Michael/0000-0001-6516-9219; Rimol, Lars M./0000-0002-1243-0396; Fennema-Notestine, Christine/0000-0002-6527-6361 FU NCRR NIH HHS [R01 RR016594, S10 RR019307]; NIA NIH HHS [R01 AG031224, AG018384, AG018386, AG022381, AG022982, R01 AG018384, R01 AG018386, R01 AG022381, R01 AG022982]; NIBIB NIH HHS [R01 EB006758]; NINDS NIH HHS [R01 NS039581, R01 NS052585, R21 NS072652] NR 47 TC 63 Z9 63 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2010 VL 67 IS 5 BP 493 EP 499 DI 10.1016/j.biopsych.2009.09.032 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 563BL UT WOS:000275100300014 PM 19963208 ER PT J AU Ballen, KK Shrestha, S Sobocinski, KA Zhang, MJ Bashey, A Bolwell, BJ Cervantes, F Devine, SM Gale, RP Gupta, V Hahn, TE Hogan, WJ Kroger, N Litzow, MR Marks, DI Maziarz, RT McCarthy, PL Schiller, G Schouten, HC Roy, V Wiernik, PH Horowitz, MM Giralt, SA Arora, M AF Ballen, Karen K. Shrestha, Smriti Sobocinski, Kathleen A. Zhang, Mei-Jie Bashey, Asad Bolwell, Brian J. Cervantes, Francisco Devine, Steven M. Gale, Robert Peter Gupta, Vikas Hahn, Theresa E. Hogan, William J. Kroeger, Nicolaus Litzow, Mark R. Marks, David I. Maziarz, Richard T. McCarthy, Philip L. Schiller, Gary Schouten, Harry C. Roy, Vivek Wiernik, Peter H. Horowitz, Mary M. Giralt, Sergio A. Arora, Mukta TI Outcome of Transplantation for Myelofibrosis SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Myelofibrosis; Allogeneic transplantation ID STEM-CELL TRANSPLANTATION; UNRELATED DONOR TRANSPLANTATION; AGNOGENIC MYELOID METAPLASIA; INTERNATIONAL-WORKING-GROUP; IDIOPATHIC MYELOFIBROSIS; ALLOGENEIC TRANSPLANTATION; MARROW-TRANSPLANTATION; PROGNOSTIC-FACTORS; GRUPPO-ITALIANO; SCORING SYSTEM AB Myelofibrosis is a myeloproliferative disorder incurable with conventional strategies. Several small series have reported long-term disease-free survival (DSF) after allogeneic hematopoietic cell transplantation (HCT). In this study, we analyze the outcomes of 289 patients receiving allogeneic transplantation for primary myelofibrosis between 1989 and 2002, from the database of the Center for International Bone Marrow Transplant Research (CIBMTR). The median age was 47 years (range: 18-73 years). Donors were HLA identical siblings in 162 patients, unrelated individuals in 101 patients, and HLA nonidentical family members in 26 patients. Patients were treated with a variety of conditioning regimens and graft-versus-host disease (GVHD) prophylaxis regimens. Splenectomy was performed in 65 patients prior to transplantation. The 100-day treatment-related mortality was 18% for HLA identical sibling transplants, 35% for unrelated transplants, and 19% for transplants from alternative related donors. Corresponding 5-year overall survival (OS) rates were 37%, 30%, and 40%, respectively. DFS rates were 33%, 27%, and 22%, respectively. DFS for patients receiving reduced-intensity transplants was comparable: 39% for HLA identical sibling donors and 17% for unrelated donors at 3 years. In this large retrospective series, allogeneic transplantation for myelofibrosis resulted in long-term relapse-free survival (RFS) in about one-third of patients. Biol Blood Marrow Transplant 16: 358-367 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Ballen, Karen K.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Shrestha, Smriti; Sobocinski, Kathleen A.; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Bashey, Asad] Blood & Marrow Transplant Grp Georgia, Atlanta, GA USA. [Bolwell, Brian J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Cervantes, Francisco] Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain. [Devine, Steven M.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Hahn, Theresa E.; McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Hogan, William J.; Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Kroeger, Nicolaus] Univ Hosp Hamburg Eppendorf, Hamburg, Germany. [Marks, David I.] United Bristol Healthcare, Bristol, Avon, England. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Schiller, Gary] Univ Calif Los Angeles, Los Angeles, CA USA. [Schouten, Harry C.] Univ Hosp Maastricht, Maastricht, Netherlands. [Roy, Vivek] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Wiernik, Peter H.] New York Med Coll, Bronx, NY USA. [Wiernik, Peter H.] Montefiore N Div, Bronx, NY USA. [Giralt, Sergio A.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 0 Emerson,Suite 118, Boston, MA 02114 USA. EM kballen@partners.org FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI) [5U01HL069294]; National Institute of Allergy and Infectious Diseases (NIAID); 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. 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 In-vitrogen 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; PDL BioPharma, Inc; Pfizer Inc; Pharmion Corporation; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; Teva Pharmaceutical Industries;; THERAKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government. NR 42 TC 97 Z9 100 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 MAR PY 2010 VL 16 IS 3 BP 358 EP 367 DI 10.1016/j.bbmt.2009.10.025 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 584DO UT WOS:000276730800008 PM 19879949 ER PT J AU Nakamae, H Storer, BE Storb, R Storek, J Chauncey, TR Pulsipher, MA Petersen, FB Wade, JC Maris, MB Bruno, B Panse, J Petersdorf, E Woolfrey, A Maloney, DG Sandmaier, BM AF Nakamae, Hirohisa Storer, Barry E. Storb, Rainer Storek, Jan Chauncey, Thomas R. Pulsipher, Michael A. Petersen, Finn B. Wade, James C. Maris, Michael B. Bruno, Benedetto Panse, Jens Petersdorf, Effie Woolfrey, Ann Maloney, David G. Sandmaier, Brenda M. TI Low-Dose Total Body Irradiation and Fludarabine Conditioning for HLA Class I-Mismatched Donor Stem Cell Transplantation and Immunologic Recovery in Patients with Hematologic Malignancies: A Multicenter Trial SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Nonmyeloablative allogeneic hematopoietic stem cell transplantation; HLA-class I mismatched donor; Low-dose total body irradiation; Fludarabine ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; MATCHED UNRELATED DONORS; PERIPHERAL-BLOOD; SOMATIC MUTATION; B-CELLS; LEUKEMIA; ALLELES; RECONSTITUTION; PROPHYLAXIS AB HLA-mismatched grafts are a viable alternative source for patients without HLA-matched donors receiving ablative hematopoietic cell transplantation (HCT), although their use in reduced intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT has been not well established. Here, we extended HCT to recipients of HLA class I-mismatched grafts to investigate whether NMA conditioning can establish stable donor engraftment. Fifty-nine patients were conditioned with fludarabine (Flu) 90 mg/m(2) and 2 Gy total body irradiation (TBI), followed by immunosuppression with cyclosporine (CsA) 5.0 mg/kg twice a day and mycophenolate mofetil (MMF) 15 mg/kg 3 times a day for transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stern cells (PBSCs) from related (n = 5) or unrelated donors (n = 54) with I antigen +/- I allele HLA class I mismatch or 2 HLA class I allele mismatches. Sustained donor engraftment was observed in 95% of the evaluable patients. The incidence of grade II-IV acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) was 69% and 41%, respectively. The cumulative probability of nonrelapse mortality (NRM) was 47% at 2 years. Two-year overall and progression-free survival (OS, PFS) was 29% and 28%, respectively. NMA conditioning with Flu and low-dose TBI, followed by HCT using HLA class I-mismatched donors leads to successful engraftment and long-term survival; however, the high incidence of aGVHD and NRM needs to be addressed by alternate GVHD prophylaxis regimens. Biol Blood Marrow Transplant 16: 384-394 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Nakamae, Hirohisa; Storer, Barry E.; Storb, Rainer; Storek, Jan; Chauncey, Thomas R.; Petersdorf, Effie; Woolfrey, Ann; Maloney, David G.; Sandmaier, Brenda M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Storer, Barry E.; Storb, Rainer; Chauncey, Thomas R.; Petersdorf, Effie; Woolfrey, Ann; Maloney, David G.; Sandmaier, Brenda M.] Univ Washington, Sch Med, Seattle, WA USA. [Storek, Jan] Univ Calgary, Calgary, AB, Canada. [Chauncey, Thomas R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Pulsipher, Michael A.] Univ Utah, Salt Lake City, UT USA. [Petersen, Finn B.] Intermt Blood & Marrow Transplant Program, Salt Lake City, UT USA. [Wade, James C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Maris, Michael B.] Rocky Mt Blood & Marrow Transplantat, Denver, CO USA. [Bruno, Benedetto] Univ Turin, Turin, Italy. [Panse, Jens] Univ Hamburg, Hamburg, Germany. RP Sandmaier, BM (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,Mail Stop D1-100,POB 19024, Seattle, WA 98109 USA. EM bsandmai@fhcrc.org FU National Cancer Institute [CA 18029, CA15704]; National Heart, Lung, and Blood Institute [HL36444]; Berlex, Inc; Graduate School of Medicine, Osaka City University, Osaka, Japan; Canada Research Chairs Program; Alberta Heritage Foundation for Medical Research; Regione Piemonte: Ricerca Finalizzata [2005, 2006, 2007] FX This study was supported by grants from the National Cancer Institute (CA 18029 and CA15704) and from the National Heart, Lung, and Blood Institute (HL36444) and also by a research grant from Berlex, Inc. Hirohisa Nakamae is funded by the Graduate School of Medicine, Osaka City University, Osaka, Japan. Jan Storek is funded by the Canada Research Chairs Program and Alberta Heritage Foundation for Medical Research. Benedetto Bruno is funded by Regione Piemonte: Ricerca Finalizzata 2005, 2006, and 2007. The authors thank research nurses Michelle Bouvier and Hsien-Tzu Chen, data manager Gresford Thomas, and trial coordinator Jennifer Freese for their invaluable help in making this study possible. We also thank Mohamed L Sorror, MD, for providing the HCT-CI scores; Mika Nakamae, MD, for reviewing data; Helen Crawford, Bonnie Larson, and Sue Carbonneau for manuscript preparation; and the transplant teams, physicians, nurses, and support personnel for their care of the patients in this study. NR 50 TC 19 Z9 21 U1 0 U2 4 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 MAR PY 2010 VL 16 IS 3 BP 384 EP 394 DI 10.1016/j.bbmt.2009.11.004 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 584DO UT WOS:000276730800011 PM 19900571 ER PT J AU Hari, PN Majhail, NS Zhang, MJ Hassebroek, A Siddiqui, F Ballen, K Bashey, A Bird, J Freytes, CO Gibson, J Hale, G Holmberg, L Kamble, R Kyle, RA Lazarus, HM LeMaistre, CF Loberiza, F Maiolino, A McCarthy, PL Milone, G Omondi, N Reece, DE Seftel, M Trigg, M Vesole, D Weiss, B Wiernik, P Lee, SJ Rizzo, JD Mehta, P AF Hari, Parameswaran N. Majhail, Navneet S. Zhang, Mei-Jie Hassebroek, Anna Siddiqui, Fareeha Ballen, Karen Bashey, Asad Bird, Jenny Freytes, Cesar O. Gibson, John Hale, Gregaory Holmberg, Leona Kamble, Ram Kyle, Robert A. Lazarus, Hillard M. LeMaistre, Charles F. Loberiza, Fausto Maiolino, Angelo McCarthy, Philip L. Milone, Gustavo Omondi, Nancy Reece, Donna E. Seftel, Matthew Trigg, Michael Vesole, David Weiss, Brendan Wiernik, Peter Lee, Stephanie J. Rizzo, J. Douglas Mehta, Paulette TI Race and Outcomes of Autologous Hematopoietic Cell Transplantation for Multiple Myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Autologous hematopoietic cell transplantation; Multiple myeloma; Race; Survival; Progression-free survival ID AFRICAN-AMERICAN PATIENTS; UNITED-STATES VETERANS; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; SOCIOECONOMIC-STATUS; SURVIVAL; CANCER; CHEMOTHERAPY; WHITE; RISK AB Blacks are twice as likely to develop and die from multiple myeloma (MM), and are less likely to receive an autologous hematopoietic-cell transplant (AHCT) for MM compared to Whites. The influence of race on outcomes of AHCT for MM is not well described. We compared the probability of overall survival (OS), progression-free survival (PFS), disease progression, and nonrelapse mortality (NRM) among Black (N = 303) and White (N = 1892) recipients of AHCT for MM, who were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2005. The Black cohort was more likely to be female, and had better Karnofsky performance scores, but lower hemoglobin and albumin levels at diagnosis. Black recipients were younger and more likely to be transplanted later in their disease course. Disease stage and treatment characteristics prior to AHCT were similar between the 2 groups. Black and White recipients had similar probabilities of 5-year OS (52% versus 47%, P = .19) and PFS (19% versus 21%, P = .64) as well as cumulative incidences of disease progression (72% versus 72%, P = .97) and NRM (9% versus 8%, P = .52). In multivariate analyses, race was not associated with any of these endpoints. Black recipients of AHCT for MM have similar outcomes compared to Whites, suggesting that the reasons underlying lower rates of AHCT in Blacks need to be studied further to ensure equal access to effective therapy. Biol Blood Marrow Transplant 16: 395-402 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Hari, Parameswaran N.; Zhang, Mei-Jie; Lee, Stephanie J.; Rizzo, J. Douglas] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA. [Majhail, Navneet S.; Hassebroek, Anna] Ctr Int Blood & Marrow Transplant Res, Natl Marrow Donor Program, Minneapolis, MN USA. [Majhail, Navneet S.] Univ Minnesota, Minneapolis, MN USA. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bashey, Asad] Blood & Marrow Transplant Grp Georgia, Atlanta, GA USA. [Bird, Jenny] Bristol Haematol & Oncol Ctr, Bristol, Avon, England. [Freytes, Cesar O.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gibson, John] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. [Hale, Gregaory] Childrens Hosp, St Petersburg, FL USA. [Holmberg, Leona] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kamble, Ram] Baylor Coll Med, Houston, TX 77030 USA. [Kyle, Robert A.] Mayo Clin, Rochester, MN USA. [Lazarus, Hillard M.] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [LeMaistre, Charles F.] Texas Transplant Inst, San Antonio, TX USA. [Loberiza, Fausto] Univ Nebraska Med Ctr, Omaha, NE USA. [Maiolino, Angelo] Hosp Univ Clementino Frago Filho, Rio De Janeiro, Brazil. [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Milone, Gustavo] Angelica Ocampo Hosp & Res Ctr, Fundaleu Buenos Aires, Argentina. [Reece, Donna E.] Univ Toronto, Toronto, ON, Canada. [Seftel, Matthew] CancerCare Manitoba, Morden, MB, Canada. [Trigg, Michael] Merck & Co Inc, Wilmington, DE USA. [Vesole, David] Loyola Univ Hlth Syst, Maywood, IL USA. [Weiss, Brendan] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Wiernik, Peter] New York Med Coll, Bronx, NY USA. [Mehta, Paulette] Univ Arkansas, Little Rock, AR 72204 USA. RP Hari, PN (reprint author), Med Coll Wisconsin, CIBMTR, POB 26509,8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM phari@mcw.edu OI Hari, Parameswaran/0000-0002-8800-297X FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI) [5U01HL069294]; National Institute of Allergy and Infectious Diseases (NIAID); 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. 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; Association of Medical Microbiology and Infectious Disease Canada; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; Blood Center of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech, an Invitrogen Company; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gambro BCT, Inc.; Gamida Cell, Ltd.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; 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 Pharmaceutical Development & Commercialization, Inc.; Pall Life Sciences; PDL BioPharma, Inc; Pfizer Inc; Pharmion Corporation; Saladax Biomedical, Inc.; Schering Plough Corporation; Society for Healthcare Epidemiology of America; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex; Teva Pharmaceutical Industries; The Marrow Foundation; THERAKOS, Inc.; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. NR 28 TC 21 Z9 21 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 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2010 VL 16 IS 3 BP 395 EP 402 DI 10.1016/j.bbmt.2009.11.007 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 584DO UT WOS:000276730800012 PM 19922808 ER PT J AU Jacobson, PA Huang, JY Wu, J Kim, M Logan, B Alousi, A Grimley, M Bolanos-Meade, J Ho, V Levine, JE Weisdorf, D AF Jacobson, Pamala A. Huang, Jiayin Wu, Juan Kim, Miae Logan, Brent Alousi, Amin Grimley, Michael Bolanos-Meade, Javier Ho, Vincent Levine, John E. Weisdorf, Daniel TI Mycophenolate Pharmacokinetics and Association with Response to Acute Graft-versus-Host Disease Treatment from the Blood and Marrow Transplant Clinical Trials Network SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Mycophenolate mofetil; Mycophenolic acid; Pharmacokinetics; acute GVHD ID HEMATOPOIETIC-CELL TRANSPLANTATION; RENAL-ALLOGRAFT RECIPIENTS; KIDNEY-TRANSPLANTATION; RANDOMIZED-TRIAL; ACID EXPOSURE; PHARMACODYNAMIC RELATIONSHIP; MOFETIL BIOAVAILABILITY; DENILEUKIN DIFTITOX; STEROID-RESISTANT; ACUTE REJECTION AB There are limited data as to the effectiveness of mycophenolate mofetil (MMF) plus high-dose corticosteroids for the treatment of acute graft-versus-host disease (aGVHD), and even less data regarding the pharmacokinetic disposition and exposure response relationship of MMF in individuals with GVHD. MMF pharmacokinetics were studied in a multicenter Blood and Marrow Transplant Clinical Trials Network randomized phase 11 trial evaluating the effectiveness of MMF as one of 4 agents added to corticosteroids as treatment of aGVHD. Thirty-two of the patients randomized to receive MMF underwent pharmacokinetic sampling in weeks 1 and 2 were studied. Mean age was 41 +/- 13.6 years. Twenty one (65.6%), 5 (15.6%), 6 (18.8%) patients had a complete response (CR), partial response (PR) or lesser response by day 28, respectively. Twenty-five (78.1%), 2 (6.3%), 5 (15.6%) patients had a CR, PR, or other response by day 56 to treatment, respectively. Mycophenolic acid (MPA) pharmacokinetic measurements from weeks 1 and 2 did not correlate with CR at either day 28 or day 56 (P > .07); however, if the mean of weeks 1 and 2 total MPA troughs was >0.5 mu g/mL or that of an unbound trough was >0.015 mu g/mL, then a significantly greater proportion achieved CR + PR at days 28 and 56. CR + PR at day 28 was observed in 19 of 19 patients (100%) with a mean total trough >0.5 mg/mL, but in only 7 of 13 (54%) with a mean total trough <= 0.5 mu g/mL (P = .002). Similarly, CR + PR at day 28 was seen in 15 of 15 patients (100%) with an unbound trough concentration >0.015 mu g/mL, but in only 11 of 17 (65%) with an unbound trough concentration <= 0.015 mu g/mL (P = .02). There was no association between the pharmacokinetic measures and risk of infection by day 90 or overall survival (OS) at day 180 postrandomization. About one-half of subjects did not achieve the favorable MPA total and unbound trough concentrations. The current practice of MMF 1 gm twice daily dosing provides low plasma concentrations in many patients. Higher doses may improve the efficacy of MMF as aGVHD therapy. Biol Blood Marrow Transplant 16: 421-429 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Jacobson, Pamala A.; Huang, Jiayin; Kim, Miae] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. [Huang, Jiayin] Vertex Pharmaceut, Clin Pharmacol, Cambridge, MA USA. [Wu, Juan] EMMES Corp, Rockville, MD USA. [Logan, Brent] Med Coll Wisconsin, Dept Populat Hlth, Milwaukee, WI 53226 USA. [Alousi, Amin] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Grimley, Michael] Texas Transplant Inst, San Antonio, TX USA. [Bolanos-Meade, Javier] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Ho, Vincent] Dana Farber Canc Inst, Dept Med Oncol Hematol Oncol, Boston, MA 02115 USA. [Levine, John E.] Univ Michigan, Dept Pediat & Internal Med, Ann Arbor, MI 48109 USA. [Weisdorf, Daniel] Univ Minnesota, Sch Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. RP Jacobson, PA (reprint author), Univ Minnesota, Coll Pharm, WDH 7-151,308 Harvard St SE, Minneapolis, MN 55455 USA. EM jacob117@umn.edu OI Levine, John/0000-0002-9133-0800 FU Roche Laboratories; National Heart, Lung and Blood Institute/National Cancer Institute FX This work was supported in part by grants from Roche Laboratories and the National Heart, Lung and Blood Institute/National Cancer Institute-funded Blood and Marrow Transplant Clinical Trials Network. NR 61 TC 21 Z9 22 U1 0 U2 1 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 MAR PY 2010 VL 16 IS 3 BP 421 EP 429 DI 10.1016/j.bbmt.2009.11.010 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 584DO UT WOS:000276730800015 PM 19925875 ER PT J AU Martinez-Rumayor, AA Vazquez, J Rehman, SU Januzzi, JL AF Martinez-Rumayor, Abelardo A. Vazquez, Josue Rehman, Shafiq U. Januzzi, James L., Jr. TI Relative value of amino-terminal pro-B-type natriuretic peptide testing and radiographic standards for the diagnostic evaluation of heart failure in acutely dyspneic subjects SO BIOMARKERS LA English DT Article DE Dyspnea; heart failure; diagnosis; natriuretic peptides; biomarkers; chest radiograph ID EMERGENCY-DEPARTMENT; COST-EFFECTIVENESS; CHEST RADIOGRAPHY; CARE; ECHOCARDIOGRAPHY; UTILITY; RISK AB To define more clearly the relationship between the information provided by the chest radiograph (CXR) and the natriuretic peptide (NT-proBNP) test as part of the evaluation of dyspneic patients presenting to the emergency department with suspected acute heart failure (HF), we evaluated the PRIDE cohort of 599 patients with and without HF, focusing on blinded NT-proBNP and unblinded CXR information. Clinical characteristics and diagnostic performance for each test were compared. We found that NT-proBNP measurement is superior to routine CXR interpretation for diagnosis or exclusion of acute HF and that normal CXR results should not be used to exclude HF in this population. C1 [Rehman, Shafiq U.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Martinez-Rumayor, Abelardo A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Vazquez, Josue] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Roche Diagnostics; SiemensDiagnostics; Critical Diagnostics FX Dr. Januzzi has received grant support from Roche Diagnostics, SiemensDiagnostics, and Critical Diagnostics. Dr. Martinez-Rumayor, Dr. Rehman and Dr. Vazquez have nothing to disclose. NR 22 TC 4 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD MAR PY 2010 VL 15 IS 2 BP 175 EP 182 DI 10.3109/13547500903411087 PG 8 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 612OA UT WOS:000278907900010 PM 19911943 ER PT J AU Ogdie, A Li, J Dai, L Paessler, ME Yu, X Diaz-Torne, C Akmatov, M Schumacher, HR Pessler, F AF Ogdie, A. Li, J. Dai, L. Paessler, M. E. Yu, X. Diaz-Torne, C. Akmatov, M. Schumacher, H. R. Pessler, F. TI Identification of broadly discriminatory tissue biomarkers of synovitis with binary and multicategory receiver operating characteristic analysis SO BIOMARKERS LA English DT Article DE Computational biology; gene expression; growth factors/cytokines/inflammatory mediators ID WAR-VETERANS-ILLNESS; RHEUMATOID-ARTHRITIS; SEPTIC ARTHRITIS; LABORATORY TESTS; JOINT PAIN; ROC CURVE; ARTHROPATHIES; ANGIOGENESIS; BIOPSY AB Immunohistochemical synovial tissue biomarkers are used increasingly to classify arthropathies, study their pathogenesis, and to measure disease activity in clinical trials. We have used receiver operating characteristic (ROC) analysis to quantify the discriminatory abilities of markers for common inflammatory cells (subintimal CD15, CD68, CD3, CD20, CD38, and lining CD68), proliferating cells (Ki-67) and blood vessels (von Willebrand factor, vWF) among inflammatory (chronic septic arthritis, early arthritis and rheumatoid arthritis (RA)) and degenerative arthropathies (osteoarthritis (OA) and orthopedic arthropathies) and normal synovium. Six of the eight markers distinguished accurately between RA and the degenerative arthropathies (area under the curve (AUC) 0.91-0.97), whereas subintimal CD68 (AUC 0.92) and Ki-67 (AUC 0.87) distinguished best between OA and normal synovium. Fold differences in mean expression correlated only modestly with AUCs (r(2) = 0.44). Multicategory ROC analysis ranked Ki-67, subintimal CD68, and CD15 as discriminating best among all six sample groups, and thus identified them as the most broadly applicable markers. C1 [Akmatov, M.; Pessler, F.] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany. [Ogdie, A.; Schumacher, H. R.] Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Li, J.] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore. [Dai, L.] Sun Yat Sen Univ, Affiliated Hosp 2, Guangzhou 510275, Guangdong, Peoples R China. [Diaz-Torne, C.] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Paessler, M. E.] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. [Yu, X.] Tradit Chinese Med Western Med Hosp, Cangzhou, Hebei, Peoples R China. [Dai, L.; Yu, X.; Diaz-Torne, C.; Schumacher, H. R.] Philadelphia VA Med Ctr, Div Rheumatol, Philadelphia, PA USA. [Pessler, F.] Tech Univ Dresden, Klin & Poliklin Kinder & Jugendmed, Dresden, Germany. RP Pessler, F (reprint author), Helmholtz Ctr Infect Res, Inhoffenstr 7, D-38124 Braunschweig, Germany. EM frank.pessler@helmholtz-hzi.de RI Li, Jialiang/B-9132-2014; OI Li, Jialiang/0000-0002-9704-4135; Ogdie, Alexis/0000-0002-4639-0775; Cesar, Diaz-Torne/0000-0001-6275-7699 FU National Institutes of Health [T32-CA 09140]; American College of Rheumatology/Research and Education Foundation; German Federal Ministry for Education and Science [SGP 08/A01] FX We thank Gilda Clayburne for expert technical assistance, Irene Loglisci, Roxann Thompson, Valice Matthews and John Romano (Philadelphia VA Medical Center, Department of Pathology) for help with histology, Lan X. Chen (Presbyterian Hospital, Philadelphia, PA) for helpful discussion and Angela Rosen-Wolff (University Children's Hospital, Technical University of Dresden, Germany) for helpful discussion and a critical reading of the manuscript. Support is gratefully acknowledged through National Institutes of Health Training Grant T32-CA 09140, a 2007-8 American College of Rheumatology/Research and Education Foundation Amgen Pediatric Rheumatology Research Award, and International Collaboration Seed Grant SGP 08/A01 from the German Federal Ministry for Education and Science (all to F. P.). The study was approved by the institutional review boards of the Philadelphia VA Medical Center, the University of Pennsylvania and the 2nd Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). NR 23 TC 11 Z9 11 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD MAR PY 2010 VL 15 IS 2 BP 183 EP 190 DI 10.3109/13547500903411095 PG 8 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 612OA UT WOS:000278907900011 PM 19916737 ER PT J AU Wang, HJ Zhou, XH AF Wang, Huixia Judy Zhou, Xiao-Hua TI Estimation of the retransformed conditional mean in health care cost studies SO BIOMETRIKA LA English DT Article DE Conditional mean; Heteroscedastic regression model; Medical cost; Quantile regression; Skewed data; Two-part model ID QUANTILE RATIO ESTIMATION; REGRESSION QUANTILES; RISK ADJUSTMENT; 2-PART MODEL; HETEROSCEDASTICITY; EXPENDITURES; ADO AB We propose a new approach for analyzing skewed and heteroscedastic health care cost data through regression of the conditional quantiles of the transformed cost. Using the appealing equivariance property of quantiles to monotone transformations, we propose a distribution-free estimator of the conditional mean cost on the original scale. The proposed method is extended to a two-part heteroscedastic model to account for zero costs commonly seen in health care cost studies. Simulation studies indicate that the proposed estimator has competitive and more robust performance than existing estimators in various heteroscedastic models. C1 [Wang, Huixia Judy] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Zhou, Xiao-Hua] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv, Res & Dev Ctr Excellence, Seattle, WA 98101 USA. RP Wang, HJ (reprint author), N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. EM wang@stat.ncsu.edu; azhou@u.washington.edu NR 22 TC 7 Z9 7 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 EI 1464-3510 J9 BIOMETRIKA JI Biometrika PD MAR PY 2010 VL 97 IS 1 BP 147 EP 158 DI 10.1093/biomet/asp072 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 558WA UT WOS:000274778000011 ER PT J AU Tohen, M Frank, E Bowden, CL Colom, F Ghaemi, NS Yatham, LN Malhi, GS Calabrese, JR Nolen, WA Vieta, E Kapczinski, F Goodwin, GM Suppes, T Sachs, GS Chengappa, KNR Grunze, H Mitchell, PB Kanba, S Berk, M AF Tohen, M. Frank, E. Bowden, C. L. Colom, F. Ghaemi, N. S. Yatham, L. N. Malhi, G. S. Calabrese, J. R. Nolen, W. A. Vieta, E. Kapczinski, F. Goodwin, G. M. Suppes, T. Sachs, G. S. Chengappa, K. N. R. Grunze, H. Mitchell, P. B. Kanba, S. Berk, M. TI The International Society for Bipolar Disorders (ISBD) Task Force on the Nomenclature of Course and Outcome in Bipolar Disorders SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 4th Biennial Conference of the International-Society-for-Bipolar-Disorders CY MAR 17-20, 2010 CL Sao Paulo, BRAZIL SP Int Soc Bipolar Disorders C1 [Tohen, M.; Bowden, C. L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Frank, E.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Colom, F.; Vieta, E.] Univ Barcelona, Bipolar Disorders Program, Hosp Clin, Barcelona, Spain. [Ghaemi, N. S.] Tufts Med Ctr, Dept Psychiat, Boston, MA USA. [Yatham, L. N.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Malhi, G. S.] Univ Sydney, Sydney, NSW 2006, Australia. [Calabrese, J. R.] Case Western Reserve Univ, Sch Med, Mood Disorders Program, Cleveland, OH 44106 USA. [Nolen, W. A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Kapczinski, F.] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Goodwin, G. M.] Univ Oxford, Warneford Hosp, Oxford, England. [Suppes, T.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Suppes, T.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Sachs, G. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sachs, G. S.] Harvard Univ, Sch Med, Boston, MA USA. [Chengappa, K. N. R.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Grunze, H.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Mitchell, P. B.] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. [Mitchell, P. B.] Black Dog Inst, Sydney, NSW, Australia. [Kanba, S.] Kyushu Univ, Dept Neuropsychiat, Fukuoka 812, Japan. [Berk, M.] Univ Melbourne, Dept Clin & Biomed Sci, Melbourne, Vic, Australia. RI Kapczinski, Flavio/D-3175-2013; Vieta, Eduard/I-6330-2013; Ghaemi, Nassir/J-4934-2013; Nolen, Willem/E-9006-2014; Kapczinski, Flavio/J-5803-2014 OI Vieta, Eduard/0000-0002-0548-0053; NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2010 VL 12 SU 1 BP 53 EP 53 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 566BL UT WOS:000275344600193 ER PT J AU Nierenberg, AA AF Nierenberg, A. A. TI Lessons from the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) effectiveness trial: What have we learned? Where do we go from here? SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 4th Biennial Conference of the International-Society-for-Bipolar-Disorders CY MAR 17-20, 2010 CL Sao Paulo, BRAZIL SP Int Soc Bipolar Disorders C1 [Nierenberg, A. A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Depress Clin & Res Program, Boston, MA 02114 USA. [Nierenberg, A. A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2010 VL 12 SU 1 BP 62 EP 62 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 566BL UT WOS:000275344600224 ER PT J AU Sachs, G AF Sachs, G. TI Clinical effectiveness research: lessons from STEP-BD SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 4th Biennial Conference of the International-Society-for-Bipolar-Disorders CY MAR 17-20, 2010 CL Sao Paulo, BRAZIL SP Int Soc Bipolar Disorders C1 [Sachs, G.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 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 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2010 VL 12 SU 1 BP 64 EP 64 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 566BL UT WOS:000275344600230 ER PT J AU Joshi, G Wozniak, J Petty, C Vivas, F Yorks, D Biederman, J Geller, D AF Joshi, Gagan Wozniak, Janet Petty, Carter Vivas, Fe Yorks, Dayna Biederman, Joseph Geller, Daniel TI Clinical characteristics of comorbid obsessive-compulsive disorder and bipolar disorder in children and adolescents SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; comorbidity; obsessive-compulsive disorder; OCD; youth ID FAMILIAL RISK ANALYSIS; ANXIETY DISORDERS; MANIA; EXPLORATION; PREVALENCE; FEATURES; ILLNESS; IMPACT; SCALE; ONSET AB Objective: To explore bidirectional comorbidity between bipolar disorder (BPD) and obsessive-compulsive disorder (OCD) in youth and to examine the symptom profile and clinical correlates of both disorders in the context of reciprocal comorbidity and ascertainment status. Methods: Two samples of consecutively referred youth (ages 6-17 years) ascertained contemporaneously for respective studies of BPD and OCD were compared using clinical and scalar assessment and structured diagnostic interviews. Results: A total of 21% (17/82) of the BPD subjects and 15% (19/125) of the OCD subjects met DSM-III-R diagnostic criteria for both disorders. In the presence of BPD, youth with OCD more frequently experienced hoarding/saving obsessions and compulsions along with a clinical profile of greater comorbidity, poorer global functioning, and higher rate of hospitalization that is characteristic of BPD. Multiple anxiety disorders (>= 3), especially generalized anxiety disorder and social phobia, were present at a higher frequency when OCD and BPD were comorbid than otherwise. In subjects with comorbid OCD and BPD, the primary disorder of ascertainment was associated with an earlier onset and more severe impairment. Conclusions: An unexpectedly high rate of comorbidity between BPD and OCD was observed in youth irrespective of primary ascertainment diagnosis. In youth with comorbid OCD and BPD, the clinical characteristics of each disorder run true and are analogues to their clinical presentation in youth without reciprocal comorbidity, with the exception of increased risk for obsessions and compulsions of hoarding/saving and comorbidity with other anxiety disorders. C1 [Joshi, Gagan; Wozniak, Janet; Petty, Carter; Vivas, Fe; Yorks, Dayna; Biederman, Joseph; Geller, Daniel] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Boston, MA 02114 USA. [Joshi, Gagan; Wozniak, Janet; Petty, Carter; Biederman, Joseph; Geller, Daniel] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Joshi, G (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, YAW 6900,55 Fruit St, Boston, MA 02114 USA. EM joshi.gagan@mgh.harvard.edu FU Dupont Warren Fellowship Award; Norma Fine Pediatric Psychopharmacology Fellowship Fund; Pediatric Psychopharmacology Council Fund; NIMH [K08 MH01481, K08 MH01503-05]; Axon Labs,; Boehringer-Ingelheim; GlaxoSmithKline; Jazz Pharmaceuticals; Novarts,; Neurogen; Pfizer; UCB (Schwarz) Pharma FX This work has been funded in part by the Dupont Warren Fellowship Award, the Norma Fine Pediatric Psychopharmacology Fellowship Fund, and the Pediatric Psychopharmacology Council Fund, as well as NIMH K08 MH01481 (DG) and NIMH K08 MH01503-05 (JW).; GJ has received research support from Bristol-Myers Squibb as the site principal investigator on a multi-centered trial; has received support from the Ethel DuPont Warren Fellowship (2005-2006) and a Pilot Research Award from the American Academy of Child and Adolescent Psychiatry (2005); has received CME sponsored support from McNeil Pediatrics; and is a co-investigator for clinical trials sponsored by Shire, Johnson & Johnson, Pfizer, Merck, Cephalon, McNeil, Eli Lilly & Co., Abbott, Novartis, Bristol-Meyers Squibb, Organon, Otsuka, Takeda, and New River Pharmaceuticals. JW receives royalties as author of Is Your Child Bipolar?, published by Bantam Books; her spouse receives research support from Boehringer-Ingelheim, GlaxoSmithKline, UCB (Schwarz) Pharma, and Sepracor; has served as a speaker for Boehringer-Ingelheim, GlaxoSmithKline, Sanofi-aventis, Sepracor, and Takeda; and has served on the advisory boards for Axon Labs, Boehringer-Ingelheim, GlaxoSmithKline, Jazz Pharmaceuticals, Novarts, Neurogen, Pfizer, UCB (Schwarz) Pharma, and Takeda. JB currently receives research support from Alza, AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., Janssen, McNeil, Merck, Organon, Otsuka, Shire, NIMH, and NICHD; and in previous years received research support, consultation fees, or speakers fees from Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly & Co., Esai, Forest, GlaxoSmithKline, Gliatech, Janssen, McNeil, NARSAD, NIDA, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc., and Wyeth. DG has received research support from Eli Lilly & Co., Forest, GlaxoSmithKline, The Obsessive Compulsive Foundation, Tourette Syndrome Association, Wallace Foundation, McIngvale Family Foundation and NIH; has received speaker honoraria from Alza, Bristol-Myers Squibb, Eli Lilly & Co., Forest, GlaxoSmithKline, Novartis, Pfizer, Shire, and Wyeth; and has had advisory or consulting relationships with Eli Lilly & Co., Solvay, Lundbeck and GlaxoSmithKline. CP, FV, and DY have no conflicts of interest to report. NR 46 TC 15 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2010 VL 12 IS 2 BP 185 EP 195 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 574SR UT WOS:000276014200007 PM 20402711 ER PT J AU Joshi, G Mick, E Wozniak, J Geller, D Park, J Strauss, S Biederman, J AF Joshi, Gagan Mick, Eric Wozniak, Janet Geller, Daniel Park, Jennifer Strauss, Samara Biederman, Joseph TI Impact of obsessive-compulsive disorder on the antimanic response to olanzapine therapy in youth with bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; OCD; olanzapine; youth ID MANIA RATING-SCALE; ANXIETY DISORDERS; REFERRED CHILDREN; LARGE-SAMPLE; COMORBIDITY; ADOLESCENTS; RELIABILITY; AKATHISIA; VALIDITY; ILLNESS AB Objective: To compare antimanic response to olanzapine therapy in youth with bipolar disorder (BPD) based on the status of comorbidity with obsessive-compulsive disorder (OCD). Methods: Secondary analysis of identically designed 8-week open-label trials of olanzapine therapy in youth with BPD. Severity of mania assessed with the Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI) scales. Results: Of the 52 BPD subjects (mean age 8.4 +/- 3.1 years) enrolled in the olanzapine trials (mean dose 8.5 +/- 4.3 mg/day), 39% (n = 20) met criteria for comorbid OCD. Antimanic response in BPD subjects was significantly worse in the presence of comorbid OCD (YMRS mean reduction: -5.9 +/- 13.1 versus -13.7 +/- 18.8, p = 0.04; >= 30% reduction: 25% versus 63%, p = 0.008; CGI-Improvement score < 2: 25% versus 68%, p = 0.003). There was no difference in the rate of dropouts (50% versus 29%, p = 0.2) or adverse effects in BPD subjects with or without comorbid OCD. Conclusions: Less than expected antimanic response to olanzapine therapy in the presence of comorbidity with OCD suggests that OCD is an important functionally impairing psychiatric comorbidity that may impact the efficacy of antimanic agents in youth with BPD. This study is limited by its design of secondary analysis of data from trials of an uncontrolled nature. Further prospective controlled trials are warranted. C1 [Joshi, Gagan; Mick, Eric; Wozniak, Janet; Geller, Daniel; Park, Jennifer; Strauss, Samara; Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Boston, MA 02114 USA. [Joshi, Gagan; Mick, Eric; Wozniak, Janet; Geller, Daniel; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Joshi, G (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, YAW 6900,55 Fruit St, Boston, MA 02114 USA. EM joshi.gagan@mgh.harvard.edu OI Mick, Eric/0000-0001-8505-8145 FU Pediatric Psychopharmacology Council Fund; Norma Fine Pediatric Psychopharmacology Fellowship Fund; McNeil Pediatrics; Ortho-McNeil Janssen Scientific Affairs; Pfizer; Shire Pharmaceuticals; NIMH; Alza; AstraZeneca; Bristol-Myers Squibb; Eli Lilly Co.; Janssen; McNeil; Merck; Organon; Otsuka FX This work was supported by the Pediatric Psychopharmacology Council Fund and the Norma Fine Pediatric Psychopharmacology Fellowship Fund.; GJ has received research support from Bristol-Myers Squibb as the site PI on a multi-centered trial; has received support from the Ethel DuPont Warren Fellowship (2005-2006), and a Pilot Research Award from the American Academy of Child and Adolescent Psychiatry (2005); and has received CME sponsored support from McNeil Pediatrics. EM receives research support from McNeil Pediatrics, Ortho-McNeil Janssen Scientific Affairs, Pfizer, Shire Pharmaceuticals, and NIMH; and has advisory or consulting relationships with Pfizer, Shire Pharmaceuticals and Validus Pharmaceuticals. JW receives royalties as author of Is Your Child Bipolar?, published by Bantam Books; her spouse receives research support from Boehringer-Ingelheim, GlaxoSmithKline, UCB (Shwarz) Pharma, and Sepracor; has served as a speaker for BoehringerIngelheim, GlaxoSmithKline, Sanofi-Aventis, Sepracor, and Takeda; and has advising relationships with Axon Labs, Boehringer-Ingelheim, GlaxoSmithKline, Jazz Pharmaceuticals, Novarts, Neurogen, Pfizer, UCB (Shwarz) Pharma, and Takeda. DG has received research support from Eli Lilly & Co., Forest Laboratories, GlaxoSmithKline, The Obsessive Compulsive Foundation, Tourette Syndrome Association, Wallace Foundation, McIngvale Family Foundation and NIH; has received speaker honoraria from Alza, BristolMyers Squibb, Eli Lilly & Co., Forest Laboratories, GlaxoSmithKline, Novartis, Pfizer, Shire, Wyeth; and has had advisory or consulting relationships with Eli Lilly & Co., Solvay, Lundbeck and GlaxoSmithKline. JB receives research support from Alza, AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., Janssen, McNeil, Merck, Organon, Otsuka, Shire, NIMH, and NICHD; has served on the speakers bureau for Janssen, McNeil, Novartis, Shire, and UCB Pharma, Inc.; has advisory or consulting relationships with Janssen, McNeil, Novartis, and Shire; and in previous years, received research support, consultation fees, or speaker's fees for/from Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly & Co., Esai, Forest, GlaxoSmithKline, Gliatech, NARSAD, NIDA, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, The Prechter Foundation, The Stanley Foundation, and Wyeth. JP and SS have no reported conflicts of interest. NR 34 TC 15 Z9 15 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2010 VL 12 IS 2 BP 196 EP 204 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 574SR UT WOS:000276014200008 PM 20402712 ER PT J AU Wiren, KM Semirale, AA Hashimoto, JG Zhang, XW AF Wiren, Kristine M. Semirale, Anthony A. Hashimoto, Joel G. Zhang, Xiao-Wei TI Signaling pathways implicated in androgen regulation of endocortical bone SO BONE LA English DT Article DE Androgen; Androgen receptor; Osteoblast; Bone formation; BMP; TGF-beta ID GROWTH-FACTOR-BETA; DIFFERENTIATION IN-VITRO; MESENCHYMAL STEM-CELLS; OSTEOBLAST DIFFERENTIATION; ADRENAL ANDROGENS; OSTEOSARCOMA CELLS; HYPOGONADAL MEN; MALE-MICE; RECEPTOR; EXPRESSION AB Periosteal expansion is a recognized response to androgen exposure during bone development and in profoundly hypogonadal adults. However, androgen also suppresses endocortical bone formation, indicating that its effects on bone are dichotomous and envelope-specific. In fact, enhanced androgen signaling has been shown to have dramatic detrimental effects on whole bone biomechanical properties in two different transgenic models with skeletally targeted androgen receptor (AR) overexpression. As the mechanisms underlying this response are uncharacterized, we compared patterns of gene expression in periosteum-free cortical bone samples derived from AR-overexpressing transgenic male mice and their wild-type counterparts. We then assessed direct androgen effects in both wild-type and AR-overexpressing osteoblasts in primary culture. Among Major Signaling pathways associated with bone formation, focused quantitative RT-PCR (qPCR) array-based analysis of endocortical bone gene expression from wild-type vs. transgenic males identified the transforming growth factor-beta (TGF-beta) superfamily and bone morphogenetic protein (BMP) signaling as significantly altered by androgen in vivo. Bioinformatic analyses indicated proliferation, osteoblast differentiation and mineralization as major biological processes affected. Consistent with the in vivo array data and bioinformatic analyses, inhibition of differentiation observed with androgen exposure was reduced by exogenous BMP2 treatment of AR-overexpressing cultures to stimulate BMP signaling, confirming array pathway analysis. In addition, nonaromatizable dihydrotestosterone (DHT) inhibited osteoblast proliferation, differentiation and several indices of mineralization, including mineral accumulation and mineralized nodule formation in primary cultures from both wild-type and AR-transgenic mice. These findings identify a molecular mechanism based on altered BMP signaling that contributes to androgen inhibition of osteoblast differentiation and mineralization. Such detrimental effects of androgen on osteoblast function May underlie the generally disappointing results of androgen therapy. Published by Elsevier Inc. C1 [Wiren, Kristine M.; Semirale, Anthony A.; Hashimoto, Joel G.; Zhang, Xiao-Wei] Portland VA Med Ctr, Bone & Mineral Res Unit, Portland, OR 97239 USA. [Wiren, Kristine M.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Wiren, Kristine M.; Semirale, Anthony A.; Hashimoto, Joel G.; Zhang, Xiao-Wei] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP Wiren, KM (reprint author), Portland VA Med Ctr, Bone & Mineral Res Unit, P3 R&D39,3710 SW Vet Hosp Rd, Portland, OR 97239 USA. EM wirenk@ohsu.edu OI Wiren, Kristine/0000-0002-6159-4450 FU United States Army Research Acquisition Activity Award [W81XWH-05-1-0086]; National Institute of Diabetes, Digestive Kidney Disease [R01 DK067541] FX The authors would like to thank Dr. Robert Majeska (City College of New York) for helpful comments in the preparation of the manuscript. This publication was made possible by grants from the United States Army Research Acquisition Activity Award No. W81XWH-05-1-0086 (KMW) and the National Institute of Diabetes, Digestive & Kidney Disease R01 DK067541 (KMW). The information contained in this publication does not necessarily reflect the position or the policy of the government, and no official endorsement should be inferred. All work was performed in facilities provided by the Department of Veterans Affairs. NR 56 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD MAR PY 2010 VL 46 IS 3 BP 710 EP 723 DI 10.1016/j.bone.2009.10.039 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 564WJ UT WOS:000275248600019 PM 19895913 ER PT J AU Wojcik, MH Meenaghan, E Lawson, EA Misra, M Klibanski, A Miller, KK AF Wojcik, Monica H. Meenaghan, Erinne Lawson, Elizabeth A. Misra, Madhusmita Klibanski, Anne Miller, Karen K. TI Reduced amylin levels are associated with low bone mineral density in women with anorexia nervosa SO BONE LA English DT Article DE Amylin; GIP; GLP2; Anorexia nervosa; Bone mineral density ID DEPENDENT INSULINOTROPIC PEPTIDE; GLUCAGON-LIKE PEPTIDE-2; GENE-RELATED PEPTIDE; OSTEOBLAST-LIKE CELLS; PARATHYROID-HORMONE; OSTEOCLAST FUNCTION; FEMALE ADOLESCENTS; DIABETES-MELLITUS; OBESE WOMEN; GLUCOSE AB Context: Anorexia nervosa, characterized by extreme low body weight due to reduced nutrient intake, is associated with severe bone loss. Peptide hormones, including amylin, GIP, and GLP2, are released immediately after nutrient intake and may be involved in the regulation of bone turnover. Objective: To investigate fasting levels of amylin, GIP, and GLP2 and their relationships with bone mineral density (BMD) in women with anorexia nervosa compared to healthy Controls. Design: Cross-sectional. Setting: Clinical Research Center. Study participants: 15 women with anorexia nervosa and 16 healthy controls. Intervention: None. Main outcome measures: Fasting serum amylin, GIP, and GLP2, and BMD. Results: Women with anorexia nervosa had significantly lower fasting serum amylin and GIP levels than healthy controls. Fasting serum GLP2 levels were not significantly different between groups. Fasting amylin levels were positively associated with BMD and Z-score at the PA spine, total hip, and femoral neck. Fasting amylin levels were also positively associated with weight and percent fat; after controlling for these variables, amylin was still a significant predictor of BMD and Z-score at the femoral neck and of Z-score at the total hip, In the anorexia nervosa group, there was a trend toward an inverse association between amylin and C-terminal telopeptide (CTX) levels (R = -0.47, p = 0.08). GIP and GLP2 levels did not predict BMD at ally site. Conclusion: Decreased secretion of amylin may be a mechanism through which reduced nutrient intake adversely affects BMD in anorexia nervosa. (C) 2009 Elsevier Inc. All rights reserved. C1 [Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM KKMiller@Partners.org FU NIH [MO1 RR01066, 1 UL1 RR025758-01, R01 DK052625] FX We thank the nurses and bionutritionists of the Massachusetts General Hospital Clinical Translational Research Center, and the patients who participated in the study. This work was supported in part by the following grants: NIH grants MO1 RR01066, 1 UL1 RR025758-01 and R01 DK052625. NR 56 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD MAR PY 2010 VL 46 IS 3 BP 796 EP 800 DI 10.1016/j.bone.2009.11.014 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 564WJ UT WOS:000275248600030 PM 19931436 ER PT J AU Eelen, G Vanoirbeek, E Verlinden, L Gijsbers, R Beullens, I Van Camp, M Paik, JH DePinho, R Bouillon, R Verstuyf, A AF Eelen, Guy Vanoirbeek, Els Verlinden, Lieve Gijsbers, Rik Beullens, Ine Van Camp, Mark Paik, Ji-Hye DePinho, Ronald Bouillon, Roger Verstuyf, Annemieke TI Forkhead Box O (FoxO) Transcription Factors in the Actions of 1,25-Dihydroxyvitamin D-3 on Osteoblasts SO BONE LA English DT Meeting Abstract CT IBMS Davos Workshop on Bone Biology and Therapeutics CY MAR 14-19, 2010 CL Davos, SWITZERLAND SP Int Bone & Mineral Soc C1 [Eelen, Guy; Vanoirbeek, Els; Verlinden, Lieve; Beullens, Ine; Van Camp, Mark; Bouillon, Roger; Verstuyf, Annemieke] KULeuven, Lab Expt Med & Endocrinol LEGENDO, Leuven, Belgium. [Gijsbers, Rik] KULeuven, Lab Mol Virol & Gene Therapy, Leuven, Belgium. [Paik, Ji-Hye; DePinho, Ronald] DFCI, Dept Med Oncol, Boston, MA USA. RI Verlinden, Lieve/E-6517-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAR PY 2010 VL 46 SU 1 MA 105 BP S48 EP S48 DI 10.1016/j.bone.2010.01.108 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 574RC UT WOS:000276009300106 ER PT J AU Smith, M AF Smith, Matthew TI Denosumab to Prevent Disease and Treatment-Related Skeletal Complications in Men with Prostate Cancer. Emerging Evidence SO BONE LA English DT Meeting Abstract CT IBMS Davos Workshop on Bone Biology and Therapeutics CY MAR 14-19, 2010 CL Davos, SWITZERLAND SP Int Bone & Mineral Soc C1 [Smith, Matthew] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAR PY 2010 VL 46 SU 1 MA 26 BP S17 EP S18 DI 10.1016/j.bone.2010.01.029 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 574RC UT WOS:000276009300027 ER PT J AU Ho, V Kim, H Aldridge, J Kao, G Liney, D Koreth, J Armand, P Cutler, C Antin, J Soiffer, R Alyea, E AF Ho, V. Kim, H. Aldridge, J. Kao, G. Liney, D. Koreth, J. Armand, P. Cutler, C. Antin, J. Soiffer, R. Alyea, E. TI Matched unrelated donor is associated with lower relapse than matched related donor in reduced-intensity conditioning transplantation: implications for graft-versus-malignancy effect SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantat/9th Meeting of the EBMT Data-Management-Group/26th Meeting of the EBMT Nurses Group/2nd EBMT Qual Management Meeting CY MAR 21-24, 2010 CL Vienna, AUSTRIA SP European Grp Blood & Marrow Transplantat, EBMT Data Management Grp, EBMT Nurses Grp C1 [Ho, V.; Kim, H.; Aldridge, J.; Kao, G.; Liney, D.; Koreth, J.; Armand, P.; Cutler, C.; Antin, J.; Soiffer, R.; Alyea, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2010 VL 45 SU 2 BP S68 EP S69 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 595LF UT WOS:000277611300166 ER PT J AU Jacobsen, E Aldridge, J Kim, H Ho, V Cutler, C Koreth, J Fisher, D Armand, P Alyea, E Freedman, A Soiffer, R Antin, J AF Jacobsen, E. Aldridge, J. Kim, H. Ho, V. Cutler, C. Koreth, J. Fisher, D. Armand, P. Alyea, E. Freedman, A. Soiffer, R. Antin, J. TI A large, single-centre experience with allogeneic stem cell transplantation for T-cell non-Hodgkin lymphoma SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantat/9th Meeting of the EBMT Data-Management-Group/26th Meeting of the EBMT Nurses Group/2nd EBMT Qual Management Meeting CY MAR 21-24, 2010 CL Vienna, AUSTRIA SP European Grp Blood & Marrow Transplantat, EBMT Data Management Grp, EBMT Nurses Grp C1 [Jacobsen, E.; Aldridge, J.; Kim, H.; Ho, V.; Cutler, C.; Koreth, J.; Fisher, D.; Armand, P.; Alyea, E.; Freedman, A.; Soiffer, R.; Antin, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2010 VL 45 SU 2 BP S248 EP S248 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 595LF UT WOS:000277611301090 ER PT J AU Koreth, J Stevenson, K Kim, H McDonough, S Ho, V Alyea, E Cutler, C Armand, P Antin, J Ritz, J Soiffer, R AF Koreth, J. Stevenson, K. Kim, H. McDonough, S. Ho, V. Alyea, E. Cutler, C. Armand, P. Antin, J. Ritz, J. Soiffer, R. TI Daily low-dose interleukin-2 administration in steroid-refractory chronic graft-versus-host disease is feasible, safe, and efficacious; with preferential regulatory T-cell expansion SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantat/9th Meeting of the EBMT Data-Management-Group/26th Meeting of the EBMT Nurses Group/2nd EBMT Qual Management Meeting CY MAR 21-24, 2010 CL Vienna, AUSTRIA SP European Grp Blood & Marrow Transplantat, EBMT Data Management Grp, EBMT Nurses Grp C1 [Koreth, J.; Stevenson, K.; Kim, H.; McDonough, S.; Ho, V.; Alyea, E.; Cutler, C.; Armand, P.; Antin, J.; Ritz, J.; Soiffer, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2010 VL 45 SU 2 BP S131 EP S131 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 595LF UT WOS:000277611300321 ER PT J AU Martin, PJ Uberti, JP Soiffer, RJ Klingemann, H Waller, EK Daly, A Herrmann, RP Visani, G Bernardo, ME Schwerdtfeger, R Kebriaei, P AF Martin, P. J. Uberti, J. P. Soiffer, R. J. Klingemann, H. Waller, E. K. Daly, A. Herrmann, R. P. Visani, G. Bernardo, M. E. Schwerdtfeger, R. Kebriaei, P. TI Prochymal (R) improves response rates in patients with steroid-refractory acute graft-versus-host disease involving the liver and gut: results of a randomized, placebo-controlled, multicentre phase III trial in GvHD SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantat/9th Meeting of the EBMT Data-Management-Group/26th Meeting of the EBMT Nurses Group/2nd EBMT Qual Management Meeting CY MAR 21-24, 2010 CL Vienna, AUSTRIA SP European Grp Blood & Marrow Transplantat, EBMT Data Management Grp, EBMT Nurses Grp C1 [Martin, P. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Uberti, J. P.] Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Soiffer, R. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Klingemann, H.] Tufts Med Ctr, Boston, MA USA. [Waller, E. K.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Daly, A.] Peter Lougheed Ctr, Calgary, AB, Canada. [Herrmann, R. P.] Royal Perth Hosp, Perth, WA, Australia. [Visani, G.] Universita Studi Pesaro, Pesaro, Italy. [Bernardo, M. E.] Fondaz IRCCS, Pioliclin San Matteo, Pavia, Italy. [Schwerdtfeger, R.] Deutsch Klin Diagnost, D-6200 Wiesbaden, Germany. [Kebriaei, P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 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 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2010 VL 45 SU 2 BP S17 EP S17 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 595LF UT WOS:000277611300041 ER PT J AU Timmermann, L Pauls, KAM Wieland, K Jech, R Kurlemann, G Sharma, N Gill, SS Haenggeli, CA Hayflick, SJ Hogarth, P Leenders, KL Limousin, P Malanga, CJ Moro, E Ostrem, JL Revilla, FJ Santens, P Schnitzler, A Tisch, S Valldeoriola, F Vesper, J Volkmann, J Woitalla, D Peker, S AF Timmermann, L. Pauls, K. A. M. Wieland, K. Jech, R. Kurlemann, G. Sharma, N. Gill, S. S. Haenggeli, C. A. Hayflick, S. J. Hogarth, P. Leenders, K. L. Limousin, P. Malanga, C. J. Moro, E. Ostrem, J. L. Revilla, F. J. Santens, P. Schnitzler, A. Tisch, S. Valldeoriola, F. Vesper, J. Volkmann, J. Woitalla, D. Peker, S. TI Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation SO BRAIN LA English DT Article DE Neurodegeneration with brain iron accumulation; dystonia; deep brain stimulation; globus pallidus ID HALLERVORDEN-SPATZ-SYNDROME; KINASE-ASSOCIATED NEURODEGENERATION; PRIMARY GENERALIZED DYSTONIA; GLOBUS-PALLIDUS; INTRATHECAL BACLOFEN; TARDIVE DYSTONIA; DISEASE; INTERNUS; HETEROGENEITY; PALLIDOTOMY AB Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty with speech and swallowing, pain and respiratory distress. Several case reports and one case series have been published concerning therapeutic outcome of pallidal deep brain stimulation in dystonia caused by neurodegeneration with brain iron degeneration, reporting mostly favourable outcomes. However, with case studies, there may be a reporting bias towards favourable outcome. Thus, we undertook this multi-centre retrospective study to gather worldwide experiences with bilateral pallidal deep brain stimulation in patients with neurodegeneration with brain iron accumulation. A total of 16 centres contributed 23 patients with confirmed neurodegeneration with brain iron accumulation and bilateral pallidal deep brain stimulation. Patient details including gender, age at onset, age at operation, genetic status, magnetic resonance imaging status, history and clinical findings were requested. Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale-Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale-Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected. Data were collected once preoperatively and at 2-6 and 9-15 months postoperatively. The primary outcome measure was change in severity of dystonia. The mean improvement in severity of dystonia was 28.5% at 2-6 months and 25.7% at 9-15 months. At 9-15 months postoperatively, 66.7% of patients showed an improvement of 20% or more in severity of dystonia, and 31.3% showed an improvement of 20% or more in disability. Global quality of life ratings showed a median improvement of 83.3% at 9-15 months. Severity of dystonia preoperatively and disease duration predicted improvement in severity of dystonia at 2-6 months; this failed to reach significance at 9-15 months. The study confirms that dystonia in neurodegeneration with brain iron accumulation improves with bilateral pallidal deep brain stimulation, although this improvement is not as great as the benefit reported in patients with primary generalized dystonias or some other secondary dystonias. The patients with more severe dystonia seem to benefit more. A well-controlled, multi-centre prospective study is necessary to enable evidence-based therapeutic decisions and better predict therapeutic outcomes. C1 [Timmermann, L.; Pauls, K. A. M.; Wieland, K.] Univ Cologne, Neurol Klin & Poliklin, Uniklin Koln, D-50924 Cologne, Germany. [Jech, R.] Charles Univ Prague, Dept Neurol, Fac Med 1, Prague, Czech Republic. [Jech, R.] Gen Teaching Hosp, Prague, Czech Republic. [Kurlemann, G.] Univ Childrens Hosp, Dept Paediat Neurol, Munster, Germany. [Sharma, N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sharma, N.] Harvard Univ, Sch Med, Boston, MA USA. [Gill, S. S.] Frenchay Hosp, Inst Neurosci, Bristol BS16 1LE, Avon, England. [Haenggeli, C. A.] Hop Enfants, Geneva, Switzerland. [Hayflick, S. J.; Hogarth, P.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Leenders, K. L.] Univ Groningen, Univ Med Ctr Groningen, Dept Neurol, NL-9713 AV Groningen, Netherlands. [Limousin, P.; Tisch, S.] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, Unit Funct Neurosurg, London, England. [Malanga, C. J.] Univ N Carolina, Div Child Neurol, Dept Neurol, Chapel Hill, NC USA. [Moro, E.] Univ Toronto, Toronto Western Hosp, Div Neurol, Toronto, ON M5T 2S8, Canada. [Ostrem, J. L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Revilla, F. J.] Univ Cincinnati, Dept Neurol, Movement Disorders Ctr, Cincinnati, OH USA. [Santens, P.] Ghent Univ Hosp, Dept Neurol, B-9000 Ghent, Belgium. [Schnitzler, A.] Univ Dusseldorf, Dept Neurol, Inst Clin Neurosci & Med Psychol, D-4000 Dusseldorf, Germany. [Valldeoriola, F.] Univ Barcelona, Hosp Clin, Inst Neurociencies, Barcelona, Spain. [Vesper, J.] Univ Dusseldorf, Dept Neurosurg, Dusseldorf, Germany. [Volkmann, J.] Univ Kiel, Dept Neurol, D-2300 Kiel, Germany. [Woitalla, D.] Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, D-4630 Bochum, Germany. [Peker, S.] Acibadem Univ, Sch Med, Hosp Neurol Sci, Dept Neurosurg, Istanbul, Turkey. RP Timmermann, L (reprint author), Univ Cologne, Neurol Klin & Poliklin, Uniklin Koln, Kerpener Str 62, D-50924 Cologne, Germany. EM lars.timmermann@uk-koeln.de RI santens, patrick/O-2505-2013; Schnitzler, Alfons/K-4625-2014; OI Schnitzler, Alfons/0000-0002-6414-7939; Malanga, C.J./0000-0003-4808-3995; Volkmann, Jens/0000-0002-9570-593X; Santens, Patrick/0000-0002-8886-9776 FU Hoffnungsbaum e.V; Kluh-Foundation; Manfred-and-Ursula-Muller-Foundation; German Bundesministerium fur Bildung und Forschung; Czech Ministry of Education [MSM 0021620849]; Brain Research Trust UK; Action Medical Research; [IGAMZ 1A/8629-5]; [GACR 309/09/1145] FX Hoffnungsbaum e.V. (to A.P., C.W., L.T.); the Kluh-Foundation (to L. T.); the Manfred-and-Ursula-Muller-Foundation (to L. T.); the German Bundesministerium fur Bildung und Forschung (BMBF, German Ministry for Education and Research: to L. T.); the Research Program MSM 0021620849 of the Czech Ministry of Education (to R. J.) and by grants IGAMZ 1A/8629-5 and GACR 309/09/1145 (to R. J.); Brain Research Trust UK (to S. T.); and Action Medical Research (to S. T.). NR 39 TC 75 Z9 79 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2010 VL 133 BP 701 EP 712 DI 10.1093/brain/awq022 PN 3 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 575DI UT WOS:000276046000008 PM 20207700 ER PT J AU Hong, Z Shi, M Chung, KA Quinn, JF Peskind, ER Galasko, D Jankovic, J Zabetian, CP Leverenz, JB Baird, G Montine, TJ Hancock, AM Hwang, H Pan, C Bradner, J Kang, UJ Jensen, PH Zhang, J AF Hong, Zhen Shi, Min Chung, Kathryn A. Quinn, Joseph F. Peskind, Elaine R. Galasko, Douglas Jankovic, Joseph Zabetian, Cyrus P. Leverenz, James B. Baird, Geoffrey Montine, Thomas J. Hancock, Aneeka M. Hwang, Hyejin Pan, Catherine Bradner, Joshua Kang, Un J. Jensen, Poul H. Zhang, Jing TI DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease SO BRAIN LA English DT Article DE cerebrospinal fluid; Parkinson's disease; biomarker; DJ-1; alpha-synuclein ID HUMAN PLASMA; ELISA; MITOCHONDRIA; PROGRESSION; DISORDERS; DEMENTIA; COMPLEX; PROTEIN; MARKER AB Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinson's disease. Both DJ-1 and alpha-synuclein, two proteins critically involved in Parkinson's disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein species detected by different antibodies, limited numbers of patients in some studies, or inadequate control of several important variables. In this study, the nature of DJ-1 and alpha-synuclein in human cerebrospinal fluid was studied by a combination of western blotting, gel filtration and mass spectrometry. Sensitive and quantitative Luminex assays detecting most, if not all, species of DJ-1 and alpha-synuclein in human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of DJ-1 and alpha-synuclein from 117 patients with Parkinson's disease, 132 healthy individuals and 50 patients with Alzheimer's disease were analysed using newly developed, highly sensitive Luminex technology while controlling for several major confounders. A total of 299 individuals and 389 samples were analysed. The results showed that cerebrospinal fluid DJ-1 and alpha-synuclein levels were dependent on age and influenced by the extent of blood contamination in cerebrospinal fluid. Both DJ-1 and alpha-synuclein levels were decreased in Parkinson's patients versus controls or Alzheimer's patients when blood contamination was controlled for. In the population aged >= 65 years, when cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and alpha-synuclein, respectively, the sensitivity and specificity for patients with Parkinson's disease versus controls were 90 and 70% for DJ-1, and 92 and 58% for alpha-synuclein. A combination of the two markers did not enhance the test performance. There was no association between DJ-1 or alpha-synuclein and the severity of Parkinson's disease. Taken together, this represents the largest scale study for DJ-1 or alpha-synuclein in human cerebrospinal fluid so far, while using newly established sensitive Luminex assays, with controls for multiple variables. We have demonstrated that total DJ-1 and alpha-synuclein in human cerebrospinal fluid are helpful diagnostic markers for Parkinson's disease, if variables such as blood contamination and age are taken into consideration. C1 [Hong, Zhen; Shi, Min; Montine, Thomas J.; Hancock, Aneeka M.; Hwang, Hyejin; Pan, Catherine; Bradner, Joshua; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Hong, Zhen] Sichuan Univ, Dept Neurol, W China Med Sch, Chengdu 610064, Sichuan, Peoples R China. [Chung, Kathryn A.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Peskind, Elaine R.; Leverenz, James B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [Peskind, Elaine R.; Zabetian, Cyrus P.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Galasko, Douglas] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Parkinsons Dis Ctr, Houston, TX 77030 USA. [Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA. [Zabetian, Cyrus P.; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98104 USA. [Baird, Geoffrey] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98104 USA. [Kang, Un J.] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. [Jensen, Poul H.] Univ Aarhus, Dept Med Biochem, Aarhus, Denmark. RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, HMC Box 359635,325 9th Ave, Seattle, WA 98104 USA. EM zhangj@uw.edu RI Shi, Min/G-6165-2012 OI Shi, Min/0000-0002-6901-2558 FU National Institutes of Health [ES004696, NS057567, AG025327, AG033398, NS060252, NS062684, AG05136, AG08017, AG08671, UL1 RR025014- 01]; Dana Foundation; Michael J. Fox Foundation; The Friends of Alzheimer's Research; Alzheimer's Association of Western and Central Washington; Department of Veterans Affairs FX National Institutes of Health grants (ES004696, NS057567, AG025327, AG033398, NS060252, NS062684, AG05136, AG08017, AG08671 and UL1 RR025014- 01); Dana Foundation; The Michael J. Fox Foundation; The Friends of Alzheimer's Research; The Alzheimer's Association of Western and Central Washington; The Department of Veterans Affairs. NR 33 TC 251 Z9 260 U1 5 U2 43 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2010 VL 133 BP 713 EP 726 DI 10.1093/brain/awq008 PN 3 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 575DI UT WOS:000276046000009 PM 20157014 ER PT J AU Holtgraves, T McNamara, P Cappaert, K Durso, R AF Holtgraves, Thomas McNamara, Patrick Cappaert, Kevin Durso, Raymond TI Linguistic correlates of asymmetric motor symptom severity in Parkinson's Disease SO BRAIN AND COGNITION LA English DT Article DE Parkinson's Disease; Language performance; Motor symptom asymmetry; Lateralization of language functions ID FRONTAL-LOBE DYSFUNCTION; MESOCORTICAL DOPAMINE NEURONS; LEFT HEMIPARKINSONS-DISEASE; SENTENCE COMPREHENSION; COGNITIVE DEFICITS; SYNTAX COMPREHENSION; LANGUAGE PRODUCTION; PREFRONTAL CORTEX; NATURAL-LANGUAGE; SPEECH AB Asymmetric motor severity is common in Parkinson's Disease (PD) and provides a method for examining the neurobiologic mechanisms underlying cognitive and linguistic deficits associated with the disorder. In the present research, PD participants (N = 3 1) were assessed in terms of the asymmetry of their motor symptoms. Interviews with the participants were analyzed with the Linguistic Inquiry and Word Count (LIWC) program. Three measures of linguistic complexity - the proportion of verbs, proportion of function words, and sentence length - were found to be affected by symptom asymmetry. Greater left-side motor severity (and hence greater right-hemisphere dysfunction) was associated with the production of significantly fewer verbs, function words, and shorter sentences. Hence, the production of linguistic complexity in a natural language context was associated with relatively greater right hemisphere involvement. The potential neurobiological mechanisms underlying this effect are discussed. (C) 2009 Elsevier Inc. All rights reserved. C1 [Holtgraves, Thomas; Cappaert, Kevin] Ball State Univ, Dept Psychol Sci, Muncie, IN 47306 USA. [McNamara, Patrick; Durso, Raymond] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McNamara, Patrick; Durso, Raymond] Boston VA Healthcare Syst, Dept Neurol 127, Boston, MA 02130 USA. RP Holtgraves, T (reprint author), Ball State Univ, Dept Psychol Sci, Muncie, IN 47306 USA. EM 00t0holtgrav@bsu.edu FU NIDCD [1R01DC007956-01A2] FX This research was supported by a grant from the NIDCD: 'Pragmatic Language Skills in Patients with Parkinson's Disease', 1R01DC007956-01A2. NR 84 TC 11 Z9 11 U1 6 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD MAR PY 2010 VL 72 IS 2 BP 189 EP 196 DI 10.1016/j.bandc.2009.08.004 PG 8 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 555LP UT WOS:000274512600005 PM 19751960 ER PT J AU Yun, RJ Krystal, JH Mathalon, DH AF Yun, Richard J. Krystal, John H. Mathalon, Daniel H. TI Working Memory Overload: Fronto-Limbic Interactions and Effects on Subsequent Working Memory Function SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Functional magnetic resonance imaging; Dorsolateral prefrontal cortex; Amygdala; Working memory; Emotional-cognitive interaction ID PREFRONTAL CORTEX; VOLUNTARY SUPPRESSION; EMOTIONAL MODULATION; COGNITIVE CONTROL; TASK-PERFORMANCE; MENTAL FATIGUE; AMYGDALA; FMRI; DEPRESSION; PATHWAYS AB The human working memory system provides an experimentally useful model for examination of neural overload effects on subsequent functioning of the overloaded system. This study employed functional magnetic resonance imaging in conjunction with a parametric working memory task to characterize the behavioral and neural effects of cognitive overload on subsequent cognitive performance, with particular attention to cognitive-limbic interactions. Overloading the working memory system was associated with varying degrees of subsequent decline in performance accuracy and reduced activation of brain regions central to both task performance and suppression of negative affect. The degree of performance decline was independently predicted by three separate factors operating during the overload condition: the degree of task failure, the degree of amygdala activation, and the degree of inverse coupling between the amygdala and dorsolateral prefrontal cortex. These findings suggest that vulnerability to overload effects in cognitive functioning may be mediated by reduced amygdala suppression and subsequent amygdala-prefrontal interaction. C1 [Yun, Richard J.; Krystal, John H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Yun, Richard J.; Krystal, John H.] VA Connecticut Healthcare Syst, Psychiat Serv, West Haven, CT USA. [Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Mathalon, Daniel H.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA USA. RP Yun, RJ (reprint author), Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. EM richard.yun@yale.edu OI Mathalon, Daniel/0000-0001-6090-4974 FU NIH [T32 MH19126, T32 MH19961]; Department of Veterans Affairs; Robert L. McNeil, Jr. Fellowship in Clinical Pharmacology FX This work was supported by NIH T32 MH19126 and T32 MH19961, the Department of Veterans Affairs, and a Robert L. McNeil, Jr. Fellowship in Clinical Pharmacology. The authors declare that they have no competing financial interests. NR 39 TC 16 Z9 16 U1 4 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD MAR PY 2010 VL 4 IS 1 BP 96 EP 108 DI 10.1007/s11682-010-9089-9 PG 13 WC Neuroimaging SC Neurosciences & Neurology GA 583DK UT WOS:000276652900009 PM 20503117 ER PT J AU Li, XB Branch, CA Nierenberg, J DeLisi, LE AF Li, Xiaobo Branch, Craig A. Nierenberg, Jay DeLisi, Lynn E. TI Disturbed Functional Connectivity of Cortical Activation during Semantic Discrimination in Patients with Schizophrenia and Subjects at Genetic High-risk SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Schizophrenia; Genetic high-risk; Semantic discrimination task; fMRI; Functional connectivity ID WORKING-MEMORY; 1ST-EPISODE SCHIZOPHRENIA; SCHIZOAFFECTIVE DISORDER; LANGUAGE LATERALIZATION; THOUGHT-DISORDER; FUSIFORM GYRUS; BRAIN IMAGES; GREY-MATTER; FMRI; ROBUST AB Schizophrenia has a strong genetic component that is relevant to the understanding of the pathophysiology of the syndrome. Thus, recent investigations have shifted from studies of diagnosed patients with schizophrenia to examining their unaffected relatives. Previous studies found that during language processing, relatives thought to be at genetic high-risk for the disorder exhibit aberrant functional activation in regions of language processing, specifically in the left inferior frontal gyrus (Broca's area). However, functional connectivity among the regions involved in language pathways is not well understood. In this study, we examined the functional connectivity between a seed located in Broca's area and the remainder of the brain during a visual lexical decision task, in 20 schizophrenia patients, 21 subjects at genetic high risk for the disorder and 21 healthy controls. Both the high-risk subjects and patients showed significantly reduced activation correlations between seed and regions related to visual language processing. Compared to the high-risk subjects, the schizophrenia patients showed even fewer regions that were correlated with the seed regions. These results suggest that there is aberrant functional connectivity within cortical language circuitry in high-risk subjects and patients with schizophrenia. Broca's area, which is one of the important regions for language processing in healthy controls, had a significantly reduced role in the high-risk subjects and patients with schizophrenia. Our findings are consistent with the existence of an underlying biological disturbance that begins in genetically at risk individuals and progresses to a greater extent in those who eventually develop schizophrenia. C1 [Li, Xiaobo; Branch, Craig A.] Yeshiva Univ, Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10461 USA. [Branch, Craig A.; Nierenberg, Jay] Nathan S Kline Inst Psychiat Res, Ctr Adv Brain Imaging, Orangeburg, NY 10962 USA. [DeLisi, Lynn E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. RP Li, XB (reprint author), Yeshiva Univ, Albert Einstein Coll Med, Dept Radiol, 1300 Morris Pk Ave,Gruss 204, Bronx, NY 10461 USA. EM xli.nki.cabi@gmail.com FU NIMH [R21 MH071720] FX The authors gratefully acknowledge Dr. Hilary Bertisch from New York University Medical School, for her role in recruiting and evaluating subjects. This project was partially supported by a grant from NIMH, R21 MH071720. NR 61 TC 19 Z9 21 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD MAR PY 2010 VL 4 IS 1 BP 109 EP 120 DI 10.1007/s11682-010-9090-3 PG 12 WC Neuroimaging SC Neurosciences & Neurology GA 583DK UT WOS:000276652900010 PM 20503118 ER PT J AU O'Neil-Pirozzi, TM Goldstein, R Strangman, GE Katz, DI Glenn, MB AF O'Neil-Pirozzi, Therese M. Goldstein, Richard Strangman, Gary E. Katz, Douglas I. Glenn, Mel B. TI Test-re-test reliability of the virtual planning test in individuals with traumatic brain injury SO BRAIN INJURY LA English DT Article DE Test-re-test reliability; executive functioning; traumatic brain injury; planning; organization ID TEST-RETEST RELIABILITY; VERBAL-LEARNING TEST; EXECUTIVE FUNCTION; ECOLOGICAL VALIDITY; INTERVENTIONS; DYSFUNCTION; DEFICITS AB Primary objective: To determine test-re-test reliability of the VIrtual Planning Test (VIP) in a group of individuals with traumatic brain injury (TBI). Research design: Single-group repeated measures design. Methods and procedures: Seventy-five individuals with TBI were administered the VIP, with 6-8 weeks between the two test sessions. Main outcomes and results: Test-re-test reliability on VIP scoring parameters as measured by Pearson correlation coefficients ranged from 0.341-0.855, with five of the seven scoring parameters exhibiting r>0.6. Conclusions: Based on the findings of the current study, the VIP has overall moderate test-re-test reliability when administered to individuals with TBI. Some VIP scoring parameters, i.e. Total correct/accuracy and Total absence, demonstrated high test-re-test reliability. Others, i.e. Planning time and Total wrong order, demonstrated low test-re-test reliability. C1 [O'Neil-Pirozzi, Therese M.] Northeastern Univ, Speech Language Pathol & Audiol Dept, Boston, MA 02115 USA. [O'Neil-Pirozzi, Therese M.; Goldstein, Richard; Strangman, Gary E.; Glenn, Mel B.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Goldstein, Richard; Glenn, Mel B.] Harvard Univ, Sch Med, Boston, MA USA. [Strangman, Gary E.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Katz, Douglas I.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Katz, Douglas I.] Braintree Rehabil Hosp, Boston, MA USA. RP O'Neil-Pirozzi, TM (reprint author), Northeastern Univ, Speech Language Pathol & Audiol Dept, 103 Forsyth Bldg, Boston, MA 02115 USA. EM t.oneil-pirozzi@neu.edu FU National Institute on Disability and Rehabilitation Research, US Department of Education [HI33A020513] FX This work was supported in part by grant #HI33A020513 from the National Institute on Disability and Rehabilitation Research, US Department of Education. NR 40 TC 3 Z9 3 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD MAR PY 2010 VL 24 IS 3 BP 509 EP 516 DI 10.3109/02699051003601697 PG 8 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 574JR UT WOS:000275985800006 PM 20184407 ER PT J AU Tsuang, D Larson, EB Li, G Shofer, JB Montine, KS Thompson, ML Sonnen, JA Crane, PK Leverenz, JB Montine, TJ AF Tsuang, Debby Larson, Eric B. Li, Ge Shofer, Jane B. Montine, Kathleen S. Thompson, Mary Lou Sonnen, Joshua A. Crane, Paul K. Leverenz, James B. Montine, Thomas J. TI Association Between Lifetime Cigarette Smoking and Lewy Body Accumulation SO BRAIN PATHOLOGY LA English DT Article DE Alzheimer's disease; Lewy body; smoking; neuropathology ID PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; CLINICAL-DIAGNOSIS; DEMENTIA; RISK; PATHOLOGY; CONSORTIUM; COHORT; HEALTH AB Cigarette smoking has been associated repeatedly in observational studies with decreased risk of Parkinson's disease (PD), but its relationship to the risk of dementia or Alzheimer's disease (AD) is inconsistent. All of these studies have used clinical diagnoses of disease. We tested the hypothesis that lifetime cigarette use might be associated with reduced risk of neuropathologic changes of Lewy-related pathology (LRP) in multiple brain regions or with reduced risk of consensus neuropathologic changes of AD in a prospective community-based study of brain aging and dementia, the Adult Changes in Thought (ACT) study. We observed that heavy lifetime cigarette smoking (> 50 pack years) was associated with significantly reduced relative risk (RR) for LRP, but not AD-type pathologic changes, after correcting for selection bias, and with significantly reduced frequency of LRP in the substantia nigra. These findings are the first of which we are aware to associate reduced LRP in human brain with any exposure, and substantiate observational studies that have associated cigarette smoking with reduced risk of PD. Although cigarette smoking is too toxic to suggest as a treatment, if confirmed, these findings may guide future therapeutic strategies that attempt to suppress LRP in human brain by other means. C1 [Montine, Kathleen S.; Sonnen, Joshua A.; Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98104 USA. [Tsuang, Debby; Li, Ge; Shofer, Jane B.; Leverenz, James B.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [Larson, Eric B.; Crane, Paul K.] Univ Washington, Dept Internal Med, Seattle, WA 98104 USA. [Thompson, Mary Lou] Univ Washington, Dept Biostat, Seattle, WA 98104 USA. [Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98104 USA. [Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Tsuang, Debby; Li, Ge; Leverenz, James B.] VA Puget Sound Hlth Care Syst, Mental Illness Ctr, Seattle, WA USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. RP Montine, TJ (reprint author), Univ Washington, Dept Pathol, Box 359791,325 9th Ave, Seattle, WA 98104 USA. EM tmontine@u.washington.edu RI Crane, Paul/C-8623-2014; Sonnen, 37382016/H-3738-2016; Tsuang, Debby/L-7234-2016; OI Sonnen, 37382016/0000-0001-9267-8705; Tsuang, Debby/0000-0002-4716-1894; Crane, Paul/0000-0003-4278-7465 FU National Institutes of Health [AG05136, AG06781, AG023801, AG000258]; Nancy and Buster Alvord Endowment; VA Puget Sound Health Care System, Seattle, Washington FX This work was supported by grants from the National Institutes of Health (AG05136, AG06781, AG023801 and AG000258) and the Nancy and Buster Alvord Endowment. This material is also the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington. The authors declare that they have no conflict of interest with this work. NR 24 TC 13 Z9 13 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD MAR PY 2010 VL 20 IS 2 BP 412 EP 418 DI 10.1111/j.1750-3639.2009.00296.x PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 551WE UT WOS:000274242400013 PM 19531100 ER PT J AU Hof, PR Elder, GA AF Hof, Patrick R. Elder, Gregory A. TI Introduction to the special issue of Brain Structure and Function on transgenic modeling of neurodegenerative disorders SO BRAIN STRUCTURE & FUNCTION LA English DT Editorial Material C1 [Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Hof, Patrick R.] Mt Sinai Sch Med, Dept Geriatr & Palliat Care, New York, NY 10029 USA. [Hof, Patrick R.] Mt Sinai Sch Med, Computat Neurobiol & Imaging Ctr, New York, NY 10029 USA. [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [Elder, Gregory A.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. RP Hof, PR (reprint author), Mt Sinai Sch Med, Dept Neurosci, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM patrick.hof@mssm.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD MAR PY 2010 VL 214 IS 2-3 BP 89 EP 90 DI 10.1007/s00429-010-0243-3 PG 2 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 576EK UT WOS:000276126900001 PM 20169361 ER PT J AU Sosa, MAG De Gasperi, R Elder, GA AF Sosa, Miguel A. Gama De Gasperi, Rita Elder, Gregory A. TI Animal transgenesis: an overview SO BRAIN STRUCTURE & FUNCTION LA English DT Review DE Conditional gene inactivation; Gene targeting; Inducible transgene expression; Pronuclear injection; Transgenic animal ID EMBRYONIC STEM-CELLS; SITE-SPECIFIC RECOMBINATION; SLEEPING-BEAUTY TRANSPOSON; MEDIATED GENE-TRANSFER; INTRACYTOPLASMIC SPERM INJECTION; VERTEBRATE FUNCTIONAL GENOMICS; YEAST ARTIFICIAL CHROMOSOME; ZINC-FINGER NUCLEASES; MAMMALIAN-CELLS; RNA INTERFERENCE AB Transgenic animals are extensively used to study in vivo gene function as well as to model human diseases. The technology for producing transgenic animals exists for a variety of vertebrate and invertebrate species. The mouse is the most utilized organism for research in neurodegenerative diseases. The most commonly used techniques for producing transgenic mice involves either the pronuclear injection of transgenes into fertilized oocytes or embryonic stem cell-mediated gene targeting. Embryonic stem cell technology has been most often used to produce null mutants (gene knockouts) but may also be used to introduce subtle genetic modifications down to the level of making single nucleotide changes in endogenous mouse genes. Methods are also available for inducing conditional gene knockouts as well as inducible control of transgene expression. Here, we review the main strategies for introducing genetic modifications into the mouse, as well as in other vertebrate and invertebrate species. We also review a number of recent methodologies for the production of transgenic animals including retrovirus-mediated gene transfer, RNAi-mediated gene knockdown and somatic cell mutagenesis combined with nuclear transfer, methods that may be more broadly applicable to species where both pronuclear injection and ES cell technology have proven less practical. C1 [Sosa, Miguel A. Gama; De Gasperi, Rita] James J Peters Dept Vet Affairs Med Ctr, Res & Dev Serv, Bronx, NY 10468 USA. [Sosa, Miguel A. Gama; De Gasperi, Rita; Elder, Gregory A.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [Elder, Gregory A.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. RP Sosa, MAG (reprint author), James J Peters Dept Vet Affairs Med Ctr, Res & Dev Serv, Res & Dev 3F-20,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM miguel.gama-sosa@mssm.edu FU National Institute on Aging [AG02219, AG05138, AG20139, AG029361]; Alzheimer's Association [IIRG-07-57318]; Department of Veterans Affairs [1I01BX000342] FX Work in the authors' laboratories has been supported by the National Institute on Aging (grants AG02219, AG05138, AG20139, and AG029361), the Alzheimer's Association (IIRG-07-57318), and a Merit Award from the Department of Veterans Affairs (1I01BX000342). NR 227 TC 61 Z9 63 U1 0 U2 40 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD MAR PY 2010 VL 214 IS 2-3 BP 91 EP 109 DI 10.1007/s00429-009-0230-8 PG 19 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 576EK UT WOS:000276126900002 ER PT J AU Elder, GA Sosa, MAG De Gasperi, R Dickstein, DL Hof, PR AF Elder, Gregory A. Sosa, Miguel A. Gama De Gasperi, Rita Dickstein, Dara L. Hof, Patrick R. TI Presenilin transgenic mice as models of Alzheimer's disease SO BRAIN STRUCTURE & FUNCTION LA English DT Review DE Alzheimer's disease; Familial Alzheimer's disease; Hippocampal neurogenesis; Presenilin-1; Presenilin-2; Transgenic mice ID AMYLOID-PRECURSOR-PROTEIN; LONG-TERM POTENTIATION; KNOCK-IN MICE; FOREBRAIN-SPECIFIC PRESENILIN-1; CONDITIONAL DOUBLE-KNOCKOUT; MUTANT HUMAN PRESENILIN-1; NEURAL PROGENITOR CELLS; SYNAPTIC PLASTICITY; MOUSE MODEL; ADULT MICE AB Mutations in presenilin-1 (PS1) and presenilin-2 (PS2) cause familial Alzheimer's disease (FAD). Presenilins influence multiple molecular pathways and are best known for their role in the gamma-secretase cleavage of type I transmembrane proteins including the amyloid precursor protein (APP). PS1 and PS2 FAD mutant transgenic mice have been generated using a variety of promoters. PS1-associated FAD mutations have also been knocked into the endogenous mouse gene. PS FAD mutant mice consistently show elevations of A beta 42 with little if any effect on A beta 40. When crossed with plaque forming APP FAD mutant lines, the PS1 FAD mutants cause earlier and more extensive plaque deposition. Although single transgenic PS1 or PS2 mice do not form plaques, they exhibit a number of pathological features including age-related neuronal and synaptic loss as well as vascular pathology. They also exhibit increased susceptibility to excitotoxic injury most likely on the basis of exaggerated calcium release from the endoplasmic reticulum. Electrophysiologically long-term potentiation in the hippocampus is increased in young PS1 FAD mutant mice but this effect appears to be lost with aging. In most studies neurogenesis in the adult hippocampus is also impaired by PS1 FAD mutants. Mice in which PS1 has been conditionally knocked out in adult forebrain on a PS2 null background (PS1/2 cDKO) develop a striking neurodegeneration that mimics AD neuropathology in being associated with neuronal and synaptic loss, astrogliosis and hyperphosphorylation of tau, although it is not accompanied by plaque deposits. The relevance of PS transgenic mice as models of AD is discussed. C1 [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [Elder, Gregory A.; Sosa, Miguel A. Gama; De Gasperi, Rita] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Sosa, Miguel A. Gama; De Gasperi, Rita] James J Peters Dept Vet Affairs Med Ctr, Res & Dev Serv, Bronx, NY 10468 USA. [Dickstein, Dara L.; Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Dickstein, Dara L.; Hof, Patrick R.] Mt Sinai Sch Med, Computat Neurobiol & Imaging Ctr, New York, NY 10029 USA. [Hof, Patrick R.] Mt Sinai Sch Med, Dept Geriatr & Palliat Care, New York, NY 10029 USA. RP Elder, GA (reprint author), James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, 3E16,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM gregory.elder@mssm.edu RI Dickstein, Dara/F-3036-2013 FU National Institute on Aging [AG02219, AG05138, AG20139, AG029361]; Alzheimer's Association [IIRG-07-57318]; Department of Veterans Affairs [1I01BX000342] FX Work in the authors' laboratories has been supported by the National Institute on Aging ( grants AG02219, AG05138, AG20139, and AG029361), the Alzheimer's Association (IIRG-07-57318) and a Merit Award from the Department of Veterans Affairs (1I01BX000342). NR 138 TC 26 Z9 29 U1 2 U2 14 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD MAR PY 2010 VL 214 IS 2-3 BP 127 EP 143 DI 10.1007/s00429-009-0227-3 PG 17 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 576EK UT WOS:000276126900004 PM 19921519 ER PT J AU Yassaee, M Fiorentino, D Okawa, J Taylor, L Coley, C Troxel, AB Werth, VP AF Yassaee, M. Fiorentino, D. Okawa, J. Taylor, L. Coley, C. Troxel, A. B. Werth, V. P. TI Modification of the Cutaneous Dermatomyositis Disease Area and Severity Index, an outcome instrument SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE dermatomyositis; outcome measures ID LUPUS-ERYTHEMATOSUS; DERMATOLOGY AB Background Validated outcome measures in dermatology help standardize and improve patient care. A scoring system of skin disease severity in dermatomyositis known as the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) has been developed. Objectives To simplify and improve the tool for clinical research and care, we modified the CDASI and validated the new version, v2. Methods The original CDASI has four activity and two damage measures. The modified CDASI has three activity and two damage measures. The skin disease of 20 patients with dermatomyositis was evaluated by the same dermatologist using both the original and the modified CDASI. Global validation measures were implemented to assess overall skin disease state, skin disease activity and skin damage. Spearman's rho (r(sp)), adjusted for multiple observations on subjects, was used to determine the relationship between the two versions of the CDASI and their correlation with the physician global measures (PGMs). Results The total score and activity and damage subscores of the original and the modified CDASI correlated perfectly with each other (r(sp) = 0 99, 1 00, 1 00). The PGM-overall skin scale correlated with the total scores (r(sp) = 0 72, r(sp) = 0 76) and activity subscores (r(sp) = 0 68, r(sp) = 0 63) but not with the damage subscores (r(sp) = 0 14, r(sp) = 0 15) of the original and the modified CDASI, respectively. However, the PGM-activity and PGM-damage scales correlated with the activity (r(sp) = 0 76, r(sp) = 0 75) and damage subscores (r(sp) = 0 90, r(sp) = 0 90), respectively, of the original and the modified CDASI. Conclusions The modified CDASI is perfectly correlated with the original CDASI. It has equally good concurrent validity with the PGM-overall skin and PGM-activity scales. The CDASI subscores have equally good concurrent validity with the PGM-activity and PGM-damage scales. We suggest that PGMs of skin disease activity and damage should be assessed separately for greater specificity. The modified CDASI is a refined and equally as useful outcome measure. C1 [Yassaee, M.; Okawa, J.; Werth, V. P.] Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Yassaee, M.; Werth, V. P.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Fiorentino, D.] Stanford Univ, Dept Dermatol, Stanford, CA 94305 USA. [Taylor, L.; Coley, C.; Troxel, A. B.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu OI Fiorentino, David/0000-0001-7951-3674; Troxel, Andrea/0000-0002-1393-3075 FU Department of Veterans Health Administration, Office of Research Development, Biomedical Laboratory Research and Development; National Institutes of Health [K24-AR 02207] FX This study was supported in part by a Merit Review Grant from the Department of Veterans Health Administration, Office of Research Development, Biomedical Laboratory Research and Development and by the National Institutes of Health (NIH K24-AR 02207) to V. P. W. NR 8 TC 19 Z9 21 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAR PY 2010 VL 162 IS 3 BP 669 EP 673 DI 10.1111/j.1365-2133.2009.09521.x PG 5 WC Dermatology SC Dermatology GA 555XR UT WOS:000274550600031 PM 19863510 ER PT J AU Hubmann, R Duchler, M Schnabl, S Hilgarth, M Demirtas, D Mitteregger, D Holbl, A Vanura, K Le, T Look, T Schwarzmeier, JD Valent, P Jager, U Shehata, M AF Hubmann, Rainer Duechler, Markus Schnabl, Susanne Hilgarth, Martin Demirtas, Dita Mitteregger, Dieter Hoelbl, Andrea Vanura, Katrina Le, Trang Look, Thomas Schwarzmeier, Josef D. Valent, Peter Jaeger, Ulrich Shehata, Medhat TI NOTCH2 links protein kinase C delta to the expression of CD23 in chronic lymphocytic leukaemia (CLL) cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; CD23; NOTCH2; PKC-delta; IFN-gamma ID B-CELLS; B1B CELLS; APOPTOSIS; PATHWAYS; SURVIVAL; ANTIGEN; GAMMA; INHIBITORS; DIFFERENTIATION; INDUCTION AB P>One characteristic of chronic lymphocytic leukaemia (CLL) lymphocytes is high expression of CD23, which has previously been identified as a downstream target for NOTCH2 signalling. The mechanisms regulating NOTCH2-dependent CD23 expression, however, are largely unknown. This study showed that peripheral CLL cells overexpressed transcriptionally active NOTCH2 (N2IC), irrespective of their prognostic marker profile. When placed in culture, NOTCH2 activity was spontaneously decreased in 25 out of 31 CLL cases (81%) within 24 h. DNA-bound N2IC complexes could be maintained by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) or by gamma-interferon (IFN-gamma), two CLL characteristic inducers of CD23 expression. Inhibition of PKC-delta by RNA interference or by rottlerin antagonised PMA-induced NOTCH2 activation and also suppressed NOTCH2 activity in CLL cases with constitutively activated NOTCH2 signalling. In 23 out of 29 CLL cases tested (79%), DNA-bound N2IC complexes were found to be resistant to the gamma-secretase inhibitor (GSI) DAPT, suggesting that GSIs will be only effective in a subset of CLL cases. These data suggest that deregulation of NOTCH2 signalling is critically involved in maintaining the malignant phenotype of CLL lymphocytes and point to a link between PKC-delta and NOTCH2 signalling in the leukemic cells. C1 [Hubmann, Rainer; Duechler, Markus; Schnabl, Susanne; Hilgarth, Martin; Demirtas, Dita; Mitteregger, Dieter; Hoelbl, Andrea; Vanura, Katrina; Le, Trang; Schwarzmeier, Josef D.; Valent, Peter; Jaeger, Ulrich; Shehata, Medhat] Med Univ Vienna, Clin Internal Med 1, Dept Haematol & Haemostaseol, A-1090 Vienna, Austria. [Hubmann, Rainer; Valent, Peter] Med Univ Vienna, Ludwig Boltzmann Cluster, A-1090 Vienna, Austria. [Schnabl, Susanne; Hilgarth, Martin; Demirtas, Dita; Schwarzmeier, Josef D.; Shehata, Medhat] Med Univ Vienna, Karl Landsteiner Inst Cytokine & Tumour Microenvi, A-1090 Vienna, Austria. [Look, Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Shehata, M (reprint author), Med Univ Vienna, Clin Internal Med 1, Dept Haematol & Haemostaseol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM medhat.shehata@meduniwien.ac.at OI Hoelbl-Kovacic, Andrea/0000-0001-6219-8794 FU Austrian Science Foundation [P15100]; Austrian National Bank, 'Jubilaeumsfonds' [9448, 10819, 11051]; 'Fellinger Krebsforschungsverein' [AP001360FF, AP001840FF]; 'Initiative Krebsforschung' [UE71104005] FX The authors would like to thank Michael S. Wolfe for providing the gamma-secretase inhibitor DAPT. This work was supported by Grant No. P15100 from the Austrian Science Foundation; by the Austrian National Bank, 'Jubilaeumsfonds'-Grants No. 9448, No. 10819, and No. 11051; by the 'Fellinger Krebsforschungsverein' (AP001360FF and AP001840FF), and by the 'Initiative Krebsforschung' (UE71104005). NR 48 TC 9 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2010 VL 148 IS 6 BP 868 EP 878 DI 10.1111/j.1365-2141.2009.08024.x PG 11 WC Hematology SC Hematology GA 562ZM UT WOS:000275094900006 PM 19995395 ER PT J AU Rusby, JE Smith, BL Gui, GPH AF Rusby, J. E. Smith, B. L. Gui, G. P. H. TI Nipple-sparing mastectomy SO BRITISH JOURNAL OF SURGERY LA English DT Review ID IMMEDIATE BREAST RECONSTRUCTION; AREOLA COMPLEX INVOLVEMENT; CARCINOMA IN-SITU; SUBCUTANEOUS MASTECTOMY; LOCAL RECURRENCE; FOLLOW-UP; NEOPLASTIC INVOLVEMENT; TRANSPLANTED NIPPLE; RADIOTHERAPY ELIOT; CANCER PATIENTS AB Background: Although effective local control is the primary goal of surgery for breast cancer, the long-term aesthetic outcome is also important. Nipple-sparing mastectomy aims to address this, but there is no consensus on its clinical application. Evidence relating to oncological safety, surgical technique and early data on aesthetic outcome was reviewed. Methods: The review was based on a PubMed search using the terms 'nipple-sparing' or 'subcutaneous mastectomy' and 'breast cancer'. Results: Large pathological studies report occult nipple involvement with cancer in 5.6-31 per cent, reflecting variation in inclusion criteria. Recent clinical series with careful patient selection report local recurrence in less than 5 per cent of patients. The incidence of cancer in the retained nipple after risk-reducing mastectomy is less than I per cent. Nipple necrosis rates range Lip to 8 and 16 per cent for total and partial necrosis respectively. Variations in outcome result from differences in extent of resection, placement of incisions and type of breast reconstruction. Conclusion: Nipple-sparing mastectomy is an acceptable technique for women undergoing risk-reducing mastectomy. In the therapeutic setting, it may be offered to patients with smaller tumours; far from the nipple and favourable pathological features. Women should be counselled about nipple necrosis and the potential for local recurrence. C1 [Rusby, J. E.; Gui, G. P. H.] Royal Marsden NHS Fdn Trust, Acad Surg, London SW3 6JJ, England. [Smith, B. L.] Massachusetts Gen Hosp, Gillette Breast Ctr, Boston, MA 02114 USA. RP Gui, GPH (reprint author), Royal Marsden NHS Fdn Trust, Acad Surg, Fulham Rd, London SW3 6JJ, England. EM gerald.gui@rmh.nhs.nk NR 87 TC 75 Z9 77 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD MAR PY 2010 VL 97 IS 3 BP 305 EP 316 DI 10.1002/bjs.6970 PG 12 WC Surgery SC Surgery GA 563AT UT WOS:000275098500002 PM 20101646 ER PT J AU Wolf, AMD Wender, RC Etzioni, RB Thompson, IM D'Amico, AV Volk, RJ Brooks, DD Dash, C Guessous, I Andrews, K DeSantis, C Smith, RA AF Wolf, Andrew M. D. Wender, Richard C. Etzioni, Ruth B. Thompson, Ian M. D'Amico, Anthony V. Volk, Robert J. Brooks, Durado D. Dash, Chiranjeev Guessous, Idris Andrews, Kimberly DeSantis, Carol Smith, Robert A. TI American Cancer Society Guideline for the Early Detection of Prostate Cancer Update 2010 SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID DIGITAL RECTAL EXAMINATION; QUALITY-OF-LIFE; ANDROGEN-DEPRIVATION THERAPY; INTENSITY-MODULATED RADIOTHERAPY; RANDOMIZED CONTROLLED-TRIAL; SCREENING TRIAL; RADICAL PROSTATECTOMY; FOLLOW-UP; TRANSRECTAL ULTRASOUND; ACTIVE SURVEILLANCE AB In 2009, the American Cancer Society (ACS) Prostate Cancer Advisory Committee began the process of a complete update of recommendations for early prostate cancer detection. A series of systematic evidence reviews was conducted focusing on evidence related to the early detection of prostate cancer, test performance, harms of therapy for localized prostate cancer, and shared and informed decision making in prostate cancer screening. The results of the systematic reviews were evaluated by the ACS Prostate Cancer Advisory Committee, and deliberations about the evidence occurred at committee meetings and during conference calls. On the basis of the evidence and a consensus process, the Prostate Cancer Advisory Committee developed the guideline, and a writing committee drafted a guideline document that was circulated to the entire committee for review and revision. The document was then circulated to peer reviewers for feedback, and finally to the ACS Mission Outcomes Committee and the ACS Board of Directors for approval. The ACS recommends that asymptomatic men who have at least a 10-year life expectancy have an opportunity to make an informed decision with their health care provider about screening for prostate cancer after they receive information about the uncertainties, risks, and potential benefits associated with prostate cancer screening. Prostate cancer screening should not occur without an informed decision-making process. Men at average risk should receive this information beginning at age 50 years. Men in higher risk groups should receive this information before age 50 years. Men should either receive this information directly from their health care providers or be referred to reliable and culturally appropriate sources. Patient decision aids are helpful in preparing men to make a decision whether to be tested. CA Cancer J Clin 20 10;60:70-98. (C) 2010 American Cancer Society, Inc. C1 [Brooks, Durado D.; Andrews, Kimberly; Smith, Robert A.] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30303 USA. [Wolf, Andrew M. D.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Wender, Richard C.] Thomas Jefferson Univ, Coll Med, Dept Family & Community Med, Philadelphia, PA 19107 USA. [Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [D'Amico, Anthony V.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genitourinary Radiat Oncol, Boston, MA 02115 USA. [Volk, Robert J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Internal Med Ambulatory Treatment & Emer, Houston, TX 77030 USA. [Dash, Chiranjeev; Guessous, Idris] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Guessous, Idris] Univ Geneva, Unit Populat Epidemiol, Dept Community Med & Primary Care, Univ Hosp Geneva, Geneva, Switzerland. [DeSantis, Carol] Amer Canc Soc, Surveillance & Hlth Policy Dept, Atlanta, GA 30303 USA. RP Brooks, DD (reprint author), Amer Canc Soc, Canc Control Sci Dept, 250 Williams St, Atlanta, GA 30303 USA. EM durado.brooks@cancer.org OI Volk, Robert/0000-0001-8811-5854 NR 166 TC 351 Z9 367 U1 4 U2 42 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAR-APR PY 2010 VL 60 IS 2 BP 70 EP 98 DI 10.3322/caac.20066 PG 29 WC Oncology SC Oncology GA 568XF UT WOS:000275558700004 PM 20200110 ER PT J AU Kaufmann, M Morrow, M von Minckwitz, G Harris, JR AF Kaufmann, Manfred Morrow, Monica von Minckwitz, Gunter Harris, Jay R. CA Biedenkopf Expert Panel Members TI Locoregional Treatment of Primary Breast Cancer Consensus Recommendations From an International Expert Panel SO CANCER LA English DT Review DE locoregional treatment; breast-conserving surgery; sentinel lymph node biopsy; radiation therapy ID CARCINOMA-IN-SITU; LYMPH-NODE BIOPSY; PRIMARY SYSTEMIC TREATMENT; B-AND-C; LOCAL RECURRENCE; CONSERVING THERAPY; RANDOMIZED-TRIAL; POSTMASTECTOMY RADIOTHERAPY; POSTOPERATIVE RADIOTHERAPY; PREOPERATIVE CHEMOTHERAPY AB Guidelines for the locoregional treatment of primary breast cancer were last published by the US National Institutes of Health in 1991. Since then, new surgical and radiotherapeutic techniques have been developed, clinical trials have provided new evidence, and intriguing long-term effects have emerged from global metadatabases, A revision of these guidelines is therefore necessary and timely. To address this concern, in October 2008, a group of opinion leaders from Austria, Denmark, France, Germany, Italy, the Netherlands, the United Kingdom, and the United States who have worked and published in the field of locoregional treatment met and collectively prepared and approved the described set of recommendations for the use of surgery and radiotherapy in primary breast cancer outside of clinical trials. Cancer 2010;116:1184-91. (C) 2010 American Cancer Society. C1 [Morrow, Monica] Mem Sloan Kettering Canc Ctr, Dept Surg, Breast Serv, New York, NY 10065 USA. [Kaufmann, Manfred; von Minckwitz, Gunter] Goethe Univ Frankfurt, Dept Gynecol & Obstet, Frankfurt, Germany. [Harris, Jay R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Morrow, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Breast Serv, 1275 York Ave, New York, NY 10065 USA. EM morrow@mskcc.org FU BANSS Foundation FX This consensus symposium received financial support from the BANSS Foundation, a nonprofit body based in Biedenkopf an der Lahn, Germany. The founder of the BANSS Foundation, who died from breast cancer, wished to help extend the information resources available to clinicians and investigators in the Field of oncology. Both the symposium and the preparation of this article were conducted in an independent and unbiased fashion. NR 39 TC 99 Z9 102 U1 0 U2 12 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 MAR 1 PY 2010 VL 116 IS 5 BP 1184 EP 1191 DI 10.1002/cncr.24874 PG 8 WC Oncology SC Oncology GA 558UD UT WOS:000274772300007 PM 20087962 ER PT J AU de Moor, JS Partridge, AH Winer, EP Ligibel, J Emmons, KM AF de Moor, Janet S. Partridge, Ann H. Winer, Eric P. Ligibel, Jennifer Emmons, Karen M. TI The Role of Socioeconomic Status in Adjustment After Ductal Carcinoma In Situ SO CANCER LA English DT Article DE ductal carcinoma in situ; intraductal; noninfiltrating; social class; anxiety; depression; social support ID QUALITY-OF-LIFE; INTRADUCTAL BREAST-CANCER; SURGICAL ADJUVANT BREAST; SOCIAL SUPPORT; PSYCHOLOGICAL MORBIDITY; PSYCHOSOCIAL ADAPTATION; RISK PERCEPTION; HEALTH; WOMEN; SURVIVORS AB BACKGROUND: A large body of literature suggests that socioeconomic status (SES) is positively associated with mental and physical health. However, little research has examined the impact of SES on psychological adjustment after a major stressor. The current study examined whether SES (education and financial status) was associated with distress (anxiety and depression) in women diagnosed with ductal carcinoma in situ (DCIS). This study also explored whether social support explained the association between SES and distress and whether social support buffered the impact of low SES on distress. METHODS: A total of 487 women with newly diagnosed DCIS were enrolled in the study. Participants completed questions about sociodemographic, psychosocial, and clinical characteristics at the time of enrollment and 9 months after their diagnosis. RESULTS: Financial status was inversely associated with anxiety and depression at the 9-month follow-up. Financial status also predicted change in anxiety and depression. Women with high financial status reported a decline in anxiety and depression during the study period, whereas women with medium or low financial status reported an increase in anxiety and depression. In addition, the probability of exceeding the screening threshold suggestive of clinical depression increased with decreasing financial status. Education was not associated with anxiety or depression. The presence of social support did not explain the association between financial status and change in distress. Social support did not buffer the effect of low SES on anxiety and depression. CONCLUSIONS: Women with medium or low SES were vulnerable to escalating anxiety and depression after a DCIS diagnosis. Cancer 2010;116:1218-25. (C) 2010 American Cancer Society. C1 [de Moor, Janet S.] Ohio State Univ, Coll Publ Hlth, Div Hlth Behav & Hlth Promot, Columbus, OH 43210 USA. [Partridge, Ann H.; Winer, Eric P.; Ligibel, Jennifer; Emmons, Karen M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP de Moor, JS (reprint author), Ohio State Univ, Coll Publ Hlth, Div Hlth Behav & Hlth Promot, 454 Cunz Hall,1841 Neil Ave, Columbus, OH 43210 USA. EM jdemoor@cph.osu.edu FU Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence in Breast Cancer [5 P50 CA89393-03]; Harvard Education Program in Cancer Prevention Control [5R25CA057711-15]; Dissemination Research to Reduce Cancer Disparities [5K05CA124415-02] FX This research was supported by Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence in Breast Cancer (5 P50 CA89393-03), the Harvard Education Program in Cancer Prevention Control (5R25CA057711-15), and Dissemination Research to Reduce Cancer Disparities (5K05CA124415-02). NR 47 TC 11 Z9 11 U1 0 U2 2 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 MAR 1 PY 2010 VL 116 IS 5 BP 1218 EP 1225 DI 10.1002/cncr.24832 PG 8 WC Oncology SC Oncology GA 558UD UT WOS:000274772300011 PM 20143325 ER PT J AU Hazra, A Fuchs, CS Kawasaki, T Kirkner, GJ Hunter, DJ Ogino, S AF Hazra, Aditi Fuchs, Charles S. Kawasaki, Takako Kirkner, Gregory J. Hunter, David J. Ogino, Shuji TI Germline polymorphisms in the one-carbon metabolism pathway and DNA methylation in colorectal cancer SO CANCER CAUSES & CONTROL LA English DT Article DE SNP; One-carbon metabolism; Colorectal cancer; CIMP; DNA methylation ID METHYLENETETRAHYDROFOLATE REDUCTASE MTHFR; POPULATION-BASED SAMPLE; COLON-CANCER; MICROSATELLITE INSTABILITY; PROMOTER METHYLATION; PHENOTYPE CIMP; UNITED-STATES; NURSES HEALTH; FOLATE STATUS; CHROMOSOMAL INSTABILITY AB Dietary intake of one-carbon nutrients (methyl donors) and germline variants in the one-carbon metabolism genes may influence global DNA methylation level and methylation in promoter CpG islands. In this study, we evaluated the relationship between single nucleotide polymorphisms (SNPs) in the one-carbon metabolism pathway and DNA methylation status in colorectal cancer. Utilizing 182 colorectal cancers cases in two prospective cohort studies, we determined the CpG island methylator phenotype (CIMP) status on eight CIMP-specific promoters and measured LINE-1 methylation level that correlates well with genome-wide DNA methylation level. We genotyped 23 nonsynonymous SNPs in the one-carbon metabolism genes using buffy coat DNA. Most of the 23 SNPs in the one-carbon metabolism pathway were not significantly associated with CIMP-high status (>= 6/8 methylated promoters). However, the MTHFR 429 Ala/Ala variant (rs1801131) and the TCN2 259 Arg/Arg variant (rs1801198) were associated with CIMP-high status (MTHFR 429 multivariate odds ratio (MV OR) = 7.56; 95% confidence interval (CI), 1.32-43.3; p trend = 0.10; TCN2 259 Arg/Arg variant MV OR = 3.82; 95% CI, 1.02-14.4; p trend = 0.06). The one-carbon metabolism genotypes were not significantly associated with LINE-1 methylation, although there were modest differences in mean LINE-1 methylation levels between certain genotypes. Collectively, these exploratory data provide suggestive evidence for the association of MTHFR 429 Ala/Ala and TCN2 259 Arg/Arg and CIMP status in colorectal cancer. C1 [Hazra, Aditi; Fuchs, Charles S.; Kirkner, Gregory J.; Hunter, David J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Hazra, Aditi; Fuchs, Charles S.; Kirkner, Gregory J.; Hunter, David J.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hazra, Aditi; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Fuchs, Charles S.; Kawasaki, Takako; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Hazra, A (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM ahazra@hsph.harvard.edu FU National Institutes of Health Research [U54 CA100971, P01 CA87969, P01 CA55075, R01 CA070817, P50 CA127003, R03 CA142082, K07 CA122826]; Bennett Family Fund; Entertainment Industry Foundation's National Colorectal Cancer Research Alliance; NIH [T-32 CA 09001-30] FX This research is supported by the National Institutes of Health Research Grants U54 CA100971, P01 CA87969, P01 CA55075, R01 CA070817, P50 CA127003, R03 CA142082, and K07 CA122826 (to S. O.); the Bennett Family Fund; and the Entertainment Industry Foundation's National Colorectal Cancer Research Alliance. A. H. was supported in part by training grant NIH T-32 CA 09001-30. The content is solely the responsibility of the authors and does not necessarily represent the official views of NCI or NIH. Funding agencies did not have any role in the design of the study; the collection, analysis, or interpretation of the data; the decision to submit the manuscript for publication; or the writing of the manuscript. We deeply thank the Nurses' Health Study and Health Professionals Follow-up Study cohort participants who generously agreed to provide us with biological specimens and information through responses to questionnaires; hospitals and pathology departments throughout the US for providing us with tumor tissue materials; Walter Willett, Sue Hankinson, and many other staff members who implemented and have maintained the cohort studies; Jean-Pierre Issa, Lanlan Shen, and Liying Yan for their assistance in the LINE-1 Pyrosequencing assay; and Peter Laird and Daniel Weisenberger for their assistance in the MethyLight assay. NR 64 TC 20 Z9 20 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2010 VL 21 IS 3 BP 331 EP 345 DI 10.1007/s10552-009-9464-2 PG 15 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 573NT UT WOS:000275921300002 PM 19936946 ER PT J AU Liu, Y Perez, M Aft, RL Massman, K Robinson, E Myles, S Schootman, M Gillanders, WE Jeffe, DB AF Liu, Ying Perez, Maria Aft, Rebecca L. Massman, Kerry Robinson, Erica Myles, Stephanie Schootman, Mario Gillanders, William E. Jeffe, Donna B. TI Accuracy of Perceived Risk of Recurrence Among Patients With Early-Stage Breast Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CARCINOMA-IN-SITU; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; 15-YEAR SURVIVAL; LOCAL RECURRENCE; WOMEN; RADIOTHERAPY; MASTECTOMY; TAMOXIFEN; SURGERY AB Background: Accurate breast cancer recurrence risk perceptions might motivate health-promoting behaviors and alleviate undue anxiety. Although a few studies have examined early-stage breast cancer survivors' perceived risk of recurrence, none have assessed the accuracy of survivors' perceived risk of recurrence. Methods: First primary ductal carcinoma in situ and early-invasive breast cancer survivors reported their perceived risk of recurrence during 6- and 12-month postsurgery interviews. We estimated the patients' 10-year risk of recurrence from published clinical trials, and for early-invasive breast cancer patients, risk of distant recurrence was based on their breast cancer-specific mortality calculated using Adjuvant! Online. Patients' perceived risk was compared with their calculated risk and categorized as "Accurate," "Underestimated," "Overestimated," and "Uncertain." Multinomial logit marginal effect models were fitted using Accurate as the reference. Results: Only 17% of 531 patients accurately perceived their risk at 6 months, most of whom inaccurately perceived their risk at 12 months (P = 0.0143). Patients who were nonwhite [odds ratio (OR), 1.70; 95% confidence interval (95% CI), 1.12-2.56] and received radiation therapy (OR, 2.01; 95% CI, 1.07-3.77) were more likely to underestimate their risk. Patients with ductal carcinoma in situ (OR, 1.69; 95% CI, 1.08-2.70), lower social support (OR, 0.71; 95% CI, 0.53-0.95), and anxiety (OR, 1.58; 95% CI, 1.01-2.47) were more likely to overestimate their risk. Conclusion: Few breast cancer survivors accurately perceived their risk of recurrence. Impact: The accuracy of perceived risk may be increased by better physician-patient communications about their prognosis, provision of social support, and treatment for coexisting anxiety. Cancer Epidemiol Biomarkers Prev; 19(3); 675-80. (C) 2010 AACR. C1 [Jeffe, Donna B.] Washington Univ, Sch Med, Dept Med, Div Hlth Behav Res, St Louis, MO 63108 USA. [Aft, Rebecca L.; Gillanders, William E.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63108 USA. [Aft, Rebecca L.; Myles, Stephanie; Schootman, Mario; Gillanders, William E.; Jeffe, Donna B.] Barnes Jewish Hosp, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Aft, Rebecca L.] John Cochran Vet Adm Hosp, St Louis, MO USA. [Massman, Kerry] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Robinson, Erica] Rush Univ, Rush Med Coll, Chicago, IL 60612 USA. RP Jeffe, DB (reprint author), Washington Univ, Sch Med, Dept Med, Div Hlth Behav Res, 4444 Forest Pk Ave,Suite 6700, St Louis, MO 63108 USA. EM djeffe@dom.wustl.edu OI Schootman, Mario/0000-0003-1162-8824; Liu, Ying/0000-0001-9636-990X FU National Cancer Institute and Breast Cancer [R01CA102777]; National Cancer Institute Cancer Center [P30 CA91842] FX National Cancer Institute and Breast Cancer Stamp Fund grant no. R01CA102777 (D. B. Jeffe) and the National Cancer Institute Cancer Center Support Grant P30 CA91842 to the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, Missouri. NR 24 TC 19 Z9 19 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2010 VL 19 IS 3 BP 675 EP 680 DI 10.1158/1055-9965.EPI-09-1051 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607CF UT WOS:000278475300006 PM 20160274 ER PT J AU Linos, E Willett, WC Cho, E Frazier, L AF Linos, Eleni Willett, Walter C. Cho, Eunyoung Frazier, Lindsay TI Adolescent Diet in Relation to Breast Cancer Risk among Premenopausal Women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ATOMIC-BOMB SURVIVORS; NURSES HEALTH; VITAMIN-D; CHILDHOOD; PATTERNS; REPRODUCIBILITY; CONSUMPTION; RECALL; COHORT AB Background: Although the association between adult diet and breast cancer has been investigated extensively, large prospective studies have generally not shown a direct link between intakes of carbohydrate, fat, fiber, and other nutrients and risk of breast cancer. Adolescence may be a period of increased susceptibility to risk factors that predispose to breast cancer. Dietary risk factors could therefore be more important during early life than later in adulthood. Methods: This is a prospective observational study of 39,268 premenopausal women in the Nurses' Health Study II who completed a 124-item food frequency questionnaire on their diet during high school (HS-FFQ) in 1998, at which time participants were 34 to 53 years of age. Cox proportional hazards regression was used to estimate relative risks and 95% CIs. Results: Four hundred fifty-five incident cases of invasive breast cancer were diagnosed between 1998 and 2005. Compared with women in the lowest quintile of intake, the relative risk of breast cancer in the highest quintile of adolescent total fat consumption was 1.35 (95% confidence interval, 1.00-1.81). Adolescent consumption of saturated, monounsaturated, polyunsaturated, and trans fats was not significantly associated with breast cancer risk. Total dairy, milk, carbohydrate intake, glycemic index, glycemic load, and fiber consumed during adolescence were not significantly related to breast cancer incidence. Conclusion: Dietary fat consumed during adolescence may be associated with an elevated risk of breast cancer. Further studies to assess this relationship among postmenopausal women, and confirm these results in premenopausal women, are needed. Cancer Epidemiol Biomarkers Prev; 19(3); 689-96. (C) 2010 AACR. C1 [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.; Frazier, Lindsay] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. [Willett, Walter C.; Frazier, Lindsay] Brigham & Womens Hosp, Boston, MA 02115 USA. [Frazier, Lindsay] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Linos, Eleni] Stanford Univ, Med Ctr, Redwood City, CA 94063 USA. [Linos, Eleni; Willett, Walter C.; Cho, Eunyoung] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Linos, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 450 Broadway St,Pavill C 2nd Floor, Redwood City, CA 94063 USA. EM linos@stanford.edu RI Linos, Eleni/C-4392-2014; OI Linos, Eleni/0000-0002-5856-6301; , Eleni/0000-0003-2538-0700 FU NIH [R25 CA098566] FX Salary support from the NIH grant R25 CA098566 (E. Linos). NR 32 TC 40 Z9 40 U1 5 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2010 VL 19 IS 3 BP 689 EP 696 DI 10.1158/1055-9965.EPI-09-0802 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607CF UT WOS:000278475300008 PM 20200427 ER PT J AU Baba, Y Nosho, K Shima, K Goessling, W Chan, AT Ng, K Chan, JA Giovannucci, EL Fuchs, CS Ogino, S AF Baba, Yoshifumi Nosho, Katsuhiko Shima, Kaori Goessling, Wolfram Chan, Andrew T. Ng, Kimmie Chan, Jennifer A. Giovannucci, Edward L. Fuchs, Charles S. Ogino, Shuji TI PTGER2 Overexpression in Colorectal Cancer Is Associated with Microsatellite Instability, Independent of CpG Island Methylator Phenotype SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POPULATION-BASED SAMPLE; COLON-CANCER; MISMATCH REPAIR; CYCLOOXYGENASE-2 INHIBITORS; LINE-1 HYPOMETHYLATION; MOLECULAR-FEATURES; PIK3CA MUTATION; POOR-PROGNOSIS; BRAF MUTATION; PREVENTION AB Background: Prostaglandin-endoperoxide synthase 2 (PTGS2, the HUGO Gene Nomenclature Committee-approved official symbol for cycloxygenase-2, COX-2) and its enzymatic product prostaglandin E2 have critical roles in inflammation and carcinogenesis through the G protein-coupled receptor PTGER2 (EP2). The PTGS2 (COX-2) pathway is a promising target for cancer therapy and chemoprevention. PTGS2 (COX-2) expression in colon cancer has been inversely associated with survival as well as tumoral microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). However, the prognostic significance of PTGER2 expression or its relationship with MSI, CIMP, LINE-1 hypomethylation, or PTGS2 (COX-2) remains uncertain. Methods: Using the database of 516 colorectal cancers in two prospective cohort studies with clinical outcome data, we detected PTGER2 overexpression in 169 (33%) tumors by immunohistochemistry. We analyzed MSI using 10 microsatellite markers; CIMP by MethyLight (real-time methylation-specific PCR) on an eight-marker panel [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1]; BRAF, KRAS, PIK3CA, and methylation in LINE-1 by Pyrosequencing; and CTNNB1 (beta-catenin) and TP53 (p53) by immunohistochemistry. Results: PTGER2 overexpression was positively associated with the mucinous component (P = 0.0016), signet ring cells (P = 0.0024), CIMP-high (P = 0.0023), and MSI-high (P < 0.0001). In multivariate analysis, the significant relationship between PTGER2 and MSI-high persisted (adjusted odds ratio, 2.82; 95% confidence interval, 1.69-4.72; P < 0.0001). PTGER2 was not significantly associated with PTGS2 (COX-2), TP53, or CTNNB1 expression, patient survival, or prognosis. Conclusion: PTGER2 overexpression is associated with MSI-high in colorectal cancer. Impact: Our data imply potential roles of inflammatory reaction by PTGER2 upregulation in carcinogenic process to MSI-high colorectal cancer. Cancer Epidemiol Biomarkers Prev; 19(3); 822-31. (C) 2010 AACR. C1 [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol,Med Sch,Dept Pathol, Boston, MA 02115 USA. [Baba, Yoshifumi; Nosho, Katsuhiko; Shima, Kaori; Goessling, Wolfram; Ng, Kimmie; Chan, Jennifer A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA USA. [Baba, Yoshifumi; Nosho, Katsuhiko; Shima, Kaori; Goessling, Wolfram; Ng, Kimmie; Chan, Jennifer A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Goessling, Wolfram] Brigham & Womens Hosp, Div Gastroenterol, Cambridge, MA USA. [Goessling, Wolfram] Brigham & Womens Hosp, Div Genet, Cambridge, MA USA. [Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol,Med Sch,Dept Pathol, 44 Binney St,Room JF-215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu OI Goessling, Wolfram/0000-0001-9972-1569 FU U.S. NIH [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA107412, K07 CA122826]; Bennett Family Fund; Entertainment Industry Foundation National Colorectal Cancer Research Alliance; Japan Society for Promotion of Science; Damon Runyon Cancer Research Foundation FX Grant Support; The U.S. NIH grants P01 CA87969 (S. Hankinson), P01 CA55075 (W. Willett), P50 CA127003 (C. S. F.), K07 CA107412 (A. T. C.), and K07 CA122826 (S.O.), in part by grants from the Bennett Family Fund and the Entertainment Industry Foundation National Colorectal Cancer Research Alliance, a fellowship grant from the Japan Society for Promotion of Science (K. No), and a grant from the Damon Runyon Cancer Research Foundation (A. T. C.). These funding sponsors had no role or involvement in the study design, the collection, analysis and interpretation of data, or writing and submission of the manuscript. NR 67 TC 15 Z9 15 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2010 VL 19 IS 3 BP 822 EP 831 DI 10.1158/1055-9965.EPI-09-1154 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607CF UT WOS:000278475300023 PM 20200425 ER PT J AU Anderson, KS Wong, J Vitonis, A Crum, CP Sluss, PM LaBaer, J Cramer, D AF Anderson, Karen S. Wong, Jessica Vitonis, Allison Crum, Christopher P. Sluss, Patrick M. LaBaer, Joshua Cramer, Daniel TI p53 Autoantibodies as Potential Detection and Prognostic Biomarkers in Serous Ovarian Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SERUM CA-125 LEVELS; BREAST-CANCER; PROTEIN MICROARRAYS; ANTIBODY-RESPONSE; CELL RESPONSES; TUMOR-ANTIGENS; IMMUNE-SYSTEM; CARCINOMA; MARKERS; SURVIVAL AB Background: This study examined the value of serum p53 autoantibodies (p53-AAb) as detection and prognostic biomarkers in ovarian cancer. Methods: p53-AAb were detected by ELISA in sera obtained preoperatively from women undergoing surgery for a pelvic mass. This group included women subsequently diagnosed with invasive serous ovarian cancer (n = 60), nonserous ovarian cancers (n = 30), and women with benign disease (n = 30). Age-matched controls were selected from the general population (n = 120). Receiver operating characteristic curves were constructed to compare the values of p53-AAb, CA 125, and HE4 as a screening biomarker. Kaplan-Meier curves and Cox proportional hazards modeling were used to assess its prognostic value on survival. Results: p53-AAb were detected in 25 of 60 (41.7%) of serous cases, 4 of 30 (13.3%) nonserous cases, 3 of 30 (10%) benign disease cases, and 10 of 120 (8.3%) controls (combined P = 0.0002). p53-AAb did not significantly improve the detection of cases [area under the curve (AUC), 0.69] or the discrimination of benign versus malignant disease (AUC, 0.64) compared with CA 125 (AUC, 0.99) or HE4 (AUC, 0.98). In multivariate analysis among cases, p53-AAb correlated only with a family history of breast cancer (P = 0.01). Detectable p53 antibodies in pretreatment sera were correlated with improved overall survival (P = 0.04; hazard ratio, 0.57; 95% confidence interval, 0.33-0.97) in serous ovarian cancer. Conclusions: Antibodies to p53 are detected in the sera of 42% of patients with advanced serous ovarian cancer. Impact: Although their utility as a preoperative diagnostic biomarker, beyond CA 125 and HE4, is limited, p53-AAb are prognostic for improved overall survival. Cancer Epidemiol Biomarkers Prev; 19(3); 859-68. (C) 2010 AACR. C1 [Anderson, Karen S.; Wong, Jessica] Dana Farber Canc Inst, Canc Vaccine Ctr, Dept Med Oncol, Boston, MA 02115 USA. [Anderson, Karen S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Vitonis, Allison; Crum, Christopher P.; Cramer, Daniel] Brigham & Womens Hosp, Dept Gynecol & Reprod Biol, Boston, MA 02115 USA. [Crum, Christopher P.; Cramer, Daniel] Brigham & Womens Hosp, Div Womens & Perinatal Pathol, Dept Pathol, Boston, MA 02115 USA. [Sluss, Patrick M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [LaBaer, Joshua] Arizona State Univ, Ctr Personalized Diagnost, Biodesign Inst, Tempe, AZ USA. RP Anderson, KS (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Dept Med Oncol, HIM416,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM kanderson@partners.org FU Early Detection Research Network [U01 CA117374, UO1 CA086381]; Department of Defense [W81XWH-07-1-0080] FX Research grant from the Early Detection Research Network U01 CA117374 (K. S. Anderson and J. LaBaer), UO1 CA086381 (D. Cramer), and the Department of Defense W81XWH-07-1-0080 (K. S. Anderson). NR 54 TC 43 Z9 45 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2010 VL 19 IS 3 BP 859 EP 868 DI 10.1158/1055-9965.EPI-09-0880 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607CF UT WOS:000278475300028 PM 20200435 ER PT J AU Lee, JE Giovannucci, E Fuchs, CS Willett, WC Zeisel, SH Cho, E AF Lee, Jung Eun Giovannucci, Edward Fuchs, Charles S. Willett, Walter C. Zeisel, Steven H. Cho, Eunyoung TI Choline and Betaine Intake and the Risk of Colorectal Cancer in Men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ONE-CARBON METABOLISM; DIETARY CHOLINE; BREAST-CANCER; WOMEN AB Dietary choline and betaine have been hypothesized to decrease the risk of cancer because of their role as methyl donors in the one-carbon metabolism. However, it remains unknown whether dietary intake of choline and betaine is associated with colorectal cancer risk. We prospectively examined the associations between dietary choline and betaine intake and risk of colorectal cancer in men in the Health Professionals Follow-up Study. We followed 47,302 men and identified a total of 987 incident colorectal cancer cases from 1986 to 2004. We assessed dietary and supplemental choline and betaine intake every 4 years using a validated semi-quantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate multivariate relative risks and 95% confidence intervals. All statistical tests were two-sided. We did not find any statistically significant associations between choline intake or betaine intake and risk of colorectal cancer. Comparing the top quintile with bottom quintile, multivariate relative risks (95% confidence interval) were 0.97 (0.79-1.20; P(trend) = 0.87) for choline intake and 0.94 (0.77-1.16; P(trend) = 0.79) for betaine intake. Similarly, we observed no associations between colorectal cancer risk and choline from free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, or sphingomyelin. Our data do not support the hypothesis that choline and betaine intake is inversely associated with colorectal cancer risk. Cancer Epidemiol Biomarkers Prev; 19(3); 884-7. (C) 2010 AACR. C1 [Lee, Jung Eun; Giovannucci, Edward; Fuchs, Charles S.; Willett, Walter C.; Cho, Eunyoung] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med,Dept Med, Boston, MA 02115 USA. [Giovannucci, Edward; Willett, Walter C.; Cho, Eunyoung] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zeisel, Steven H.] Univ N Carolina, Dept Nutr, Inst Nutr Res, Chapel Hill, NC USA. RP Lee, JE (reprint author), Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med,Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM jung.lee@channing.harvard.edu OI Lee, Jung Eun/0000-0003-1141-878X FU NCI NIH HHS [R03 CA125763-01A1, CA125763, CA55075, P01 CA055075, P01 CA055075-18, R03 CA125763]; NIDDK NIH HHS [DK55865, P30 DK040561, P30 DK040561-14, R01 DK055865]; NIEHS NIH HHS [P30 ES010126] NR 14 TC 26 Z9 28 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2010 VL 19 IS 3 BP 884 EP 887 DI 10.1158/1055-9965.EPI-09-1295 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607CF UT WOS:000278475300032 PM 20160273 ER PT J AU Sarna, L Cooley, ME Brown, JK Chernecky, C Padilla, G Danao, L Chakravarty, D Elashoff, D AF Sarna, Linda Cooley, Mary E. Brown, Jean K. Chernecky, Cynthia Padilla, Geraldine Danao, Leda Chakravarty, Deepalika Elashoff, David TI Women With Lung Cancer: Quality of Life After Thoracotomy A 6-Month Prospective Study SO CANCER NURSING LA English DT Article DE Comorbidity; Dyspnea; Functional status; Lung cancer; Psychological; Quality of life; Smoking; Survivorship; Thoracotomy; Women ID LONG-TERM SURVIVORS; PULMONARY-FUNCTION; BRONCHOGENIC-CARCINOMA; BREAST-CANCER; HEALTH; SURGERY; COMORBIDITY; PERCEPTIONS; PREDICTORS; DEPRESSION AB Background: Data about health-related quality of life (QOL) after surgical treatment for lung cancer are limited. Such information can be valuable in developing appropriate nursing interventions for follow-up care for survivors. Objectives: The purposes of this study were to describe physical and emotional QOL of disease-free female non-small cell lung cancer (NSCLC) survivors and to determine characteristics associated with greater risk for disruptions. Methods: One-hundred-nineteen women surgically treated for NSCLC completed the Short-Form 36 (as a measure of physical and mental QOL) along with health status assessments (including comorbidity, depression, Center for Epidemiologic Studies-Depression Scale, smoking status, and body mass index), dyspnea (Dyspnea Index), meaning of illness, and demographic and clinical information at baseline and 3 and 6 months. Results: On average, the women were 68 years of age, diagnosed 2 years previously, had adenocarcinoma, and were treated surgically with lobectomy. The majority (66%) had comorbid disease, 29% had depressed mood (Center for Epidemiologic Studies-Depression Scale score >= 16), 8% were current smokers, 62% were overweight, 22% had dyspnea (scores >= 2), and 24% had a negative meaning of illness. Physical and emotional QOL scores were comparable to Short-Form 36 norms for older adults and exhibited little change over time. Controlling for time since diagnosis, dyspnea, and depressed mood were strongly related to disruptions in physical and emotional QOL, respectively, across the 6-month study period, with comorbid disease contributing to both models. Conclusion: Depressed mood, comorbidities, and dyspnea were factors related to poorer physical and emotional QOL. Survivors with these characteristics might benefit from greater supportive care. Implications for Practice: Screening for dyspnea, depressed mood, and comorbid illness can identify female survivors at-risk for poorer QOL after surgery. C1 [Sarna, Linda; Padilla, Geraldine] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. [Cooley, Mary E.] Phyllis F Cantor Ctr Res Nursing & Patient Care S, Dana Farber Canc Inst, Boston, MA USA. [Brown, Jean K.] SUNY Buffalo, Sch Nursing, Buffalo, NY 14260 USA. [Chernecky, Cynthia] Med Coll Georgia, Sch Nursing, Augusta, GA 30912 USA. [Danao, Leda] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Chakravarty, Deepalika] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Elashoff, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Sarna, L (reprint author), Univ Calif Los Angeles, Sch Nursing, 700 Tiverton Ave,Box 956918, Los Angeles, CA 90095 USA. EM lsarna@sonnet.ucla.edu FU Oncology Nursing Foundation Center for Leadership, Information, and Research [018652] FX This study was funded by the Oncology Nursing Foundation Center for Leadership, Information, and Research (no. 018652). NR 50 TC 23 Z9 23 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD MAR-APR PY 2010 VL 33 IS 2 BP 85 EP 92 DI 10.1097/NCC.0b013e3181be5e51 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA 568XY UT WOS:000275560700002 PM 20142740 ER PT J AU Jane-Valbuena, J Widlund, HR Perner, S Johnson, LA Dibner, AC Lin, WM Baker, AC Nazarian, RM Vijayendran, KG Sellers, WR Hahn, WC Duncan, LM Rubin, MA Fisher, DE Garraway, LA AF Jane-Valbuena, Judit Widlund, Hans R. Perner, Sven Johnson, Laura A. Dibner, Aurora C. Lin, William M. Baker, Alissa C. Nazarian, Rosalynn M. Vijayendran, Krishna G. Sellers, William R. Hahn, William C. Duncan, Lyn M. Rubin, Mark A. Fisher, David E. Garraway, Levi A. TI An Oncogenic Role for ETV1 in Melanoma SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR ER81; MALIGNANT-MELANOMA; PROSTATE-CANCER; GENE; FUSION; ACTIVATION; EXPRESSION; SARCOMA; TRANSLOCATION; MUTATIONS AB Copy gains involving chromosome 7p represent one of the most common genomic alterations found in melanomas, suggesting the presence of "driver" cancer genes. We identified several tumor samples that harbored focal amplifications situated at the peak of common chromosome 7p gains, in which the minimal common overlapping region spanned the ETV1 oncogene. Fluorescence in situ hybridization analysis revealed copy gains spanning the ETV1 locus in >40% of cases, with ETV1 amplification (>6 copies/cell) present in 13% of primary and 18% of metastatic melanomas. Melanoma cell lines, including those with ETV1 amplification, exhibited dependency on ETV1 expression for proliferation and anchorage-independent growth. Moreover, overexpression of ETV1 in combination with oncogenic NRAS(G12D) transformed primary melanocytes and promoted tumor formation in mice. ETV1 overexpression elevated microphthalmia-associated transcription factor expression in immortalized melanocytes, which was necessary for ETV1-dependent oncogenicity. These observations implicate deregulated ETV1 in melanoma genesis and suggest a pivotal lineage dependency mediated by oncogenic ETS transcription factors in this malignancy. Cancer Res; 70(5); 2075-84. (C)2010 AACR. C1 [Jane-Valbuena, Judit; Johnson, Laura A.; Dibner, Aurora C.; Lin, William M.; Baker, Alissa C.; Vijayendran, Krishna G.; Hahn, William C.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Widlund, Hans R.; Fisher, David E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Jane-Valbuena, Judit; Johnson, Laura A.; Dibner, Aurora C.; Lin, William M.; Baker, Alissa C.; Vijayendran, Krishna G.; Hahn, William C.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Nazarian, Rosalynn M.; Duncan, Lyn M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Perner, Sven; Johnson, Laura A.; Rubin, Mark A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Nazarian, Rosalynn M.; Duncan, Lyn M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Johnson, Laura A.; Lin, William M.; Hahn, William C.; Garraway, Levi A.] MIT & Harvard, Broad Inst, Cambridge, MA USA. [Sellers, William R.] Novartis Inst Biomed Res, Cambridge, MA USA. RP Garraway, LA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM levi_garraway@dfci.harvard.edu OI Rubin, Mark/0000-0002-8321-9950; Nazarian, Rosalynn/0000-0003-4003-7193 FU Department of Defense Prostate Cancer Program (Postdoctoral Traineeship Award); NIH; National Cancer Institute; Robert Wood Johnson Foundation; Prostate Cancer Foundation; Starr Cancer Consortium; Melanoma Research Alliance; Burroughs-Wellcome Fund FX We thank M. Bachrach for technical assistance. J. Jane-Valbuena and L.A. Garraway acknowledge financial support from the Department of Defense Prostate Cancer Program (Postdoctoral Traineeship Award), NIH, National Cancer Institute, Robert Wood Johnson Foundation, Prostate Cancer Foundation, Starr Cancer Consortium, Melanoma Research Alliance, and Burroughs-Wellcome Fund. D. E. Fisher is Distinguished Clinical Scholar of the Doris Duke Medical Foundation and acknowledges grant support from NIH. NR 28 TC 52 Z9 54 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 MAR 1 PY 2010 VL 70 IS 5 BP 2075 EP 2084 DI 10.1158/0008-5472.CAN-09-3092 PG 10 WC Oncology SC Oncology GA 607FZ UT WOS:000278485800035 PM 20160028 ER PT J AU Knight, CS Tallaj, JA Rayburn, BK Pamboukian, SV Bourge, R Kirklin, JK McGiffin, D Litovsky, SH AF Knight, Carrie S. Tallaj, Jose A. Rayburn, Barry K. Pamboukian, Salpy V. Bourge, Robert Kirklin, James K. McGiffin, David Litovsky, Silvio H. TI Bradycardia and syncope as a presentation of cardiac allograft rejection involving the conducting system SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE Bradycardia; Heart transplant; Rejection; Conducting system ID HEART-TRANSPLANTATION AB Post-heart transplantation bradycardic syncope and arrest could be clue to preferential rejection of the conduction system. We present six heart transplant patients with this presentation, two of whom died. The autopsy of one of those patients demonstrated severe rejection of the conduction system, with only mild rejection throughout the rest of the myocardium. We postulate that aggressive therapy for rejection and pacemaker placement may result in improved survival in heart transplant recipients with this clinical presentation. Published by Elsevier Inc. C1 [Knight, Carrie S.; Litovsky, Silvio H.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Tallaj, Jose A.; Rayburn, Barry K.; Pamboukian, Salpy V.; Bourge, Robert] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Tallaj, Jose A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Kirklin, James K.; McGiffin, David] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Tallaj, JA (reprint author), THT 338,1900 Univ Blvd, Birmingham, AL 35294 USA. EM jtallaj@uab.edu NR 9 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD MAR-APR PY 2010 VL 19 IS 2 BP 117 EP 120 DI 10.1016/j.carpath.2008.10.006 PG 4 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 610PN UT WOS:000278745800006 PM 19144548 ER PT J AU Mukhopadhyay, P Rajesh, M Batkai, S Patel, V Kashiwaya, Y Liaudet, L Evgenov, OV Mackie, K Hasko, G Pacher, P AF Mukhopadhyay, Partha Rajesh, Mohanraj Batkai, Sandor Patel, Vivek Kashiwaya, Yoshihiro Liaudet, Lucas Evgenov, Oleg V. Mackie, Ken Hasko, Gyoergy Pacher, Pal TI CB1 cannabinoid receptors promote oxidative stress and cell death in murine models of doxorubicin-induced cardiomyopathy and in human cardiomyocytes SO CARDIOVASCULAR RESEARCH LA English DT Article DE Heart failure; CB1 receptor; Endocannabinoids; Rimonabant; SR141716; AM281 ID ISCHEMIA-REPERFUSION INJURY; ENDOCANNABINOID SYSTEM; ISCHEMIA/REPERFUSION INJURY; INDUCED CARDIOTOXICITY; NITRIC-OXIDE; IN-VITRO; PEROXYNITRITE; DYSFUNCTION; MICE; SUPEROXIDE AB Here we investigated the mechanisms by which cardiovascular CB1 cannabinoid receptors may modulate the cardiac dysfunction, oxidative stress, and interrelated cell death pathways associated with acute/chronic cardiomyopathy induced by the widely used anti-tumour compound doxorubicin (DOX). Both load-dependent and -independent indices of left-ventricular function were measured by the Millar pressure-volume conductance system. Mitogen-activated protein kinase (MAPK) activation, cell-death markers, and oxidative/nitrosative stress were measured by molecular biology/biochemical methods and flow cytometry. DOX induced left-ventricular dysfunction, oxidative/nitrosative stress coupled with impaired antioxidant defense, activation of MAPK (p38 and JNK), and cell death and/or fibrosis in hearts of wide-type mice (CB1+/+), and these effects were markedly attenuated in CB1 knockouts (CB1-/-). In human primary cardiomyocytes expressing CB1 receptors (demonstrated by RT-PCR, western immunoblot, and flow cytometry) DOX, likewise the CB1 receptor agonist HU210 and the endocannabinoid anandamide (AEA), induced MAPK activation and cell death. The DOX-induced MAPK activation and cell death were significantly enhanced when DOX was co-administered with CB1 agonists AEA or HU210. Remarkably, cell death and MAPK activation induced by AEA, HU210, and DOX +/- AEA/HU210 were largely attenuated by either CB1 antagonists (rimonabant and AM281) or by inhibitors of p38 and JNK MAPKs. Furthermore, AEA or HU210 in primary human cardiomyocytes triggered increased reactive oxygen species generation. CB1 activation in cardiomyocytes may amplify the reactive oxygen/nitrogen species-MAPK activation-cell death pathway in pathological conditions when the endocannabinoid synthetic or metabolic pathways are dysregulated by excessive inflammation and/or oxidative/nitrosative stress, which may contribute to the pathophysiology of various cardiovascular diseases. C1 [Mukhopadhyay, Partha; Rajesh, Mohanraj; Batkai, Sandor; Patel, Vivek; Pacher, Pal] NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Kashiwaya, Yoshihiro] NIAAA, Lab Metab Control, NIH, Bethesda, MD 20892 USA. [Liaudet, Lucas] Univ Hosp, Dept Intens Care Med, Lausanne, Switzerland. [Evgenov, Oleg V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Mackie, Ken] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Mackie, Kenneth/B-7358-2011; Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Mackie, Ken/E-3715-2013; Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Mackie, Ken/0000-0001-8501-6199; Liaudet, Lucas/0000-0003-2670-4930 FU National Institutes of Health/NIAAA [DA11322]; Swiss National Fund for Scientific Research [PP00B-68882/1] FX This study was supported by the Intramural research program of the National Institutes of Health/NIAAA (to P. P.) and DA11322 (to K. M.), Swiss National Fund for Scientific Research Grant PP00B-68882/1 (to L. L.). NR 48 TC 71 Z9 76 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAR 1 PY 2010 VL 85 IS 4 BP 773 EP 784 DI 10.1093/cvr/cvp369 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 555DO UT WOS:000274487900017 PM 19942623 ER PT J AU Anderson, HV Rosenfield, KA White, CJ Ho, KKL Spertus, JA Jones, PG Tang, FM Cates, CU Jaff, MR Koroshetz, WJ Katzan, IL Hopkins, LN Rumsfeld, JS Brindis, RG AF Anderson, H. Vernon Rosenfield, Kenneth A. White, Christopher J. Ho, Kalon K. L. Spertus, John A. Jones, Philip G. Tang, Fengming Cates, Christopher U. Jaff, Michael R. Koroshetz, Walter J. Katzan, Irene L. Hopkins, L. Nelson Rumsfeld, John S. Brindis, Ralph G. TI Clinical Features and Outcomes of Carotid Artery Stenting by Clinical Expert Consensus Criteria: A Report From the CARE Registry SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE peripheral vascular disease; quantitative vascular angiography; total occlusions ID RISK PATIENTS; ENDARTERECTOMY; PROTECTION; PREDICTORS AB Background: In 2007, a multispecialty society task force published a clinical expert consensus document (CECD) on carotid stenting (CAS), containing recommendations for appropriate patient selection and quality of care. The CECD also inspired creation of a large, national registry of carotid revascularization, the Carotid Artery Revascularization and Endarterectomy (CARE) registry. Our goal here was to investigate whether initial CAS procedures submitted to CARE conformed to CECD recommendations, and examine their clinical outcomes. Methods: We analyzed CAS procedures for the period January 1, 2005 through December 31, 2008. These were grouped into those that conformed to CECD recommendations [CECD(+), n = 4,636, 79.8%] and those that did not [CECD(), n = 1,168, 20.2%]. Results: The CECD(+) patients were older than CECD() patients (71.5 +/- 10.3 vs. 67.6 +/- 10.3 years, P = 0.001, respectively), and more frequently had chronic kidney disease (46.9% vs. 17.8%, P = 0.001), chronic lung disease (33.0% vs. 12.4%, P = 0.001), ejection fraction <= 0.30 (13.5% vs. 5.5%, P = 0.001) and contralateral carotid artery occlusion (12.7% vs. 4.6%, P = 0.001). Clinical outcomes at 30 days were similar, including death (1.24% vs. 0.76%, P = 0.184), stroke (5.32% vs. 5.34%, P = 0.954), and death, stroke, or MI (7.04% vs. 6.95%, P = 0.944). Conclusions: Most CAS procedures submitted to CARE conformed to CECD recommendations for patient selection. For reported data, clinical outcomes at 30 days were similar for procedures meeting and those not meeting recommendations, and were similar to outcomes reported by other large registries. These findings suggest that acceptable patient selection criteria for CAS are employed as it expands beyond investigators into more widespread clinical practice. (C) 2010 Wiley-Liss, Inc. C1 [Anderson, H. Vernon] Univ Texas Hlth Sci Ctr, Div Cardiol, Houston, TX 77030 USA. [Rosenfield, Kenneth A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [White, Christopher J.] Ochsner Clin Fdn, Dept Cardiol, New Orleans, LA USA. [Ho, Kalon K. L.] Beth Israel Deaconess Med Ctr, Dept Cardiol, Boston, MA 02215 USA. [Spertus, John A.; Jones, Philip G.; Tang, Fengming] St Lukes Hosp, Mid Amer Heart Inst, Dept Cardiol, Kansas City, MO 64111 USA. [Cates, Christopher U.] Emory Univ Hosp, Dept Cardiol, Atlanta, GA 30322 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. [Katzan, Irene L.] Cleveland Clin, Cerebrovasc Ctr, Cleveland, OH 44106 USA. [Katzan, Irene L.] Cleveland Clin, Dept Neurol, Cleveland, OH 44106 USA. [Hopkins, L. Nelson] SUNY Buffalo, Millard Fillmore Hosp, Dept Neurosurg, Buffalo, NY 14260 USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Rumsfeld, John S.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Brindis, Ralph G.] Amer Coll Cardiol, Washington, DC USA. RP Anderson, HV (reprint author), Univ Texas Hlth Sci Ctr, Div Cardiol, 6431 Fannin,1246, Houston, TX 77030 USA. EM h.v.anderson@uth.tmc.edu RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 NR 10 TC 7 Z9 7 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 MAR 1 PY 2010 VL 75 IS 4 BP 519 EP 525 DI 10.1002/ccd.22333 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 582HW UT WOS:000276588600009 PM 20088016 ER PT J AU Faber, AC Wong, KK Engelman, JA AF Faber, Anthony C. Wong, Kwok-Kin Engelman, Jeffrey A. TI Differences underlying EGFR and HER2 oncogene addiction SO CELL CYCLE LA English DT Editorial Material ID TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; LUNG-CANCER; GROWTH C1 [Faber, Anthony C.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Wong, Kwok-Kin] Harvard Univ, Dana Farber Canc Inst, Ctr Canc, Ludwig Ctr, Boston, MA 02115 USA. [Wong, Kwok-Kin; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wong, Kwok-Kin] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Engelman, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. EM jengelman@partners.org FU NCI NIH HHS [K08 CA120060-04, P50 CA090578, P50 CA090578-070010, P50 CA127003, K08 CA120060, P50 CA127003-030004, R01 CA137008, R01 CA137008-02, R01 CA140594, R01 CA140594-01] NR 10 TC 29 Z9 30 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 1 PY 2010 VL 9 IS 5 BP 851 EP 852 DI 10.4161/cc.9.5.11096 PG 2 WC Cell Biology SC Cell Biology GA 578QB UT WOS:000276307700001 PM 20160489 ER PT J AU Sun, YL Jiang, XF Price, BD AF Sun, Yingli Jiang, Xiaofeng Price, Brendan D. TI Tip60 Connecting chromatin to DNA damage signaling SO CELL CYCLE LA English DT Article DE Tip60; ATM; histone methylation; H3K9me3; chromodomain; DNA repair; lysine demethylase ID DOUBLE-STRAND BREAKS; HISTONE LYSINE METHYLATION; ATM KINASE-ACTIVITY; ACTIVATION IN-VIVO; ATAXIA-TELANGIECTASIA; ACETYLTRANSFERASE ACTIVITY; AUTOPHOSPHORYLATION SITES; HETEROCHROMATIN PROTEIN-1; MRE11-RAD50-NBS1 COMPLEX; COLORECTAL-CANCER AB Cells are constantly exposed to genotoxic events that can damage DNA. To counter this, cells have evolved a series of highly conserved DNA repair pathways to maintain genomic integrity. The ATM protein kinase is a master regulator of the DNA double-strand break (DSB) repair pathway. DSBs activate ATM's kinase activity, promoting the phosphorylation of proteins involved in both checkpoint activation and DNA repair. Recent work has revealed that two DNA damage response proteins, the Tip60 acetyltransferase and the mre11-rad50-nbs1 (MRN) complex, co-operate in the activation of ATM in response to DSBs. MRN functions to target ATM and the Tip60 acetyltransferase to DSBs. Tip60's chromodomain then interacts with histone H3 trimethylated on lysine 9, activating Tip60's acetyltransferase activity and stimulating the subsequent acetylation and activation of ATM's kinase activity. These results underscore the importance of chromatin structure in regulating DNA damage signaling and emphasize how histone modifications co-ordinate DNA repair. In addition, human tumors frequently exhibit altered patterns of histone methylation. This rewriting of the histone methylation code in tumor cells may impact the efficiency of DSB repair, increasing genomic instability and contributing to the initiation and progression of cancer. C1 [Sun, Yingli; Jiang, Xiaofeng; Price, Brendan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02115 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM brendan_price@dfci.harvard.edu FU NCI [CA64585, CA93602, T32 CA09078]; DOD Breast Cancer Program FX We thank A. D'Andrea and members of the Price laboratory for critical discussions and reading of the manuscript. This work was supported by grants from the NCI (CA64585 and CA93602) and the DOD Breast Cancer Program to B. D. P., and by an NCI training grant to Y. S. (T32 CA09078). NR 101 TC 100 Z9 105 U1 1 U2 10 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 1 PY 2010 VL 9 IS 5 BP 930 EP 936 DI 10.4161/cc.9.5.10931 PG 7 WC Cell Biology SC Cell Biology GA 578QB UT WOS:000276307700026 PM 20160506 ER PT J AU Agarwal, S Daley, GQ AF Agarwal, Suneet Daley, George Q. TI AID for reprogramming SO CELL RESEARCH LA English DT Editorial Material ID DNA DEMETHYLATION; PLURIPOTENT; DEAMINASE; GENOME C1 [Agarwal, Suneet; Daley, George Q.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Hematol Oncol, 1 Blackfan Circle, Boston, MA 02115 USA. EM George.Daley@childrens.harvard.edu FU NHLBI NIH HHS [K08 HL089150] NR 12 TC 3 Z9 3 U1 0 U2 2 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD MAR PY 2010 VL 20 IS 3 BP 253 EP 255 DI 10.1038/cr.2010.30 PG 3 WC Cell Biology SC Cell Biology GA 572GS UT WOS:000275816300003 PM 20190775 ER PT J AU Bu, L Gao, XL Jiang, X Chien, KR Wang, Z AF Bu, Lei Gao, Xiaolin Jiang, Xin Chien, Kenneth R. Wang, Zhong TI Targeted conditional gene knockout in human embryonic stem cells SO CELL RESEARCH LA English DT Letter ID ZINC-FINGER NUCLEASES; HOMOLOGOUS RECOMBINATION; EFFICIENT METHOD; INTEGRASE; MICE C1 [Chien, Kenneth R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Richard Simches Res Ctr, Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Chien, KR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM kchien@partners.org; zhwang@partners.org NR 15 TC 10 Z9 11 U1 0 U2 4 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD MAR PY 2010 VL 20 IS 3 BP 379 EP 382 DI 10.1038/cr.2010.23 PG 4 WC Cell Biology SC Cell Biology GA 572GS UT WOS:000275816300013 PM 20142843 ER PT J AU Cadalbert, LC Sloss, CM Cunningham, MR Al-Mutairi, M McIntire, A Shipley, J Plevin, R AF Cadalbert, Laurence C. Sloss, Callum M. Cunningham, Margaret R. Al-Mutairi, Mashael McIntire, Alan Shipley, Janet Plevin, Robin TI Differential regulation of MAP kinase activation by a novel splice variant of human MAP kinase phosphatase-2 SO CELLULAR SIGNALLING LA English DT Article DE MAP kinase phosphatase; MAP kinase; JNK; ERK; MKP-2; DUSP4; MKP; DUSP; Tyrosine kinase ID N-TERMINAL KINASE; DUAL-SPECIFIC PHOSPHATASE; CELL ANTIGEN RECEPTOR; PROTEIN-KINASE; CATALYTIC ACTIVATION; IN-VIVO; SPECIFICITY; JNK; GENE; VHR AB MAP kinase phosphatase-2 (MKP-2) is a member of the family of dual specificity phosphatases that functions to inactivate the ERK and JNK MAP kinase signalling pathways. Here, we identify a novel human MKP-2 variant (MKP-2-S) lacking the MAP kinase binding site but retaining the phosphatase catalytic domain. Endogenous MKP-2-S transcripts and proteins were found in PC3 prostate and MDA-MB-231 breast cancer cells and also human prostate biopsies. Cellular transfection of MKP-2-S gave rise to a nuclear protein of 33 kDa which displayed phosphatase activity comparable to the formerly described long form of MKP-2 (MKP-2-L). Due to its lack of a kinase interacting motif (KIM), MKP-2-S did not bind to JNK or ERK; MKP-2-L bound ERK and to a lesser extent JNK. Protein turnover of adenoviral expressed MKP-2-S was accelerated relative to MKP-2-L, with a greater susceptibility to proteosomal-mediated degradation. MKP-2-S retained its ability to deactivate JNK in a similar manner as MKP-2-L and was an effective inhibitor of LPS-stimulated COX-2 induction. However, unlike MKP-2-L, MKP-2-S was unable to reverse serum-induced ERK activation or significantly inhibit endothelial cell proliferation. These findings reveal the occurrence of a novel splice variant of MKP-2 which is unable to bind ERK and may be significant in the dysregulation of MAP kinase activity in certain disease states, particularly in breast and prostate cancers. (C) 2009 Elsevier Inc. All rights reserved. C1 [Cadalbert, Laurence C.; Cunningham, Margaret R.; Plevin, Robin] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Div Physiol & Pharmacol, Glasgow, Lanark, Scotland. [Sloss, Callum M.] Massachusetts Gen Hosp, Surg Oncol Res Labs, Boston, MA 02114 USA. [Al-Mutairi, Mashael] Kuwait Univ, Hlth Sci Ctr, Fac Allied Hlth Sci, Dept Med Lab Sci, Safat 13110, Kuwait. [McIntire, Alan; Shipley, Janet] Male Urol Canc Res Ctr, Inst Canc Res, Sutton, Surrey, England. RP Plevin, R (reprint author), Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Div Physiol & Pharmacol, John Arbuthnott Bldg,27 Taylor St G4 0NR, Glasgow, Lanark, Scotland. EM r.plevin@strath.ac.uk OI Cadalbert, Laurence/0000-0003-1333-2146; Cunningham, Margaret/0000-0001-6454-8671 NR 31 TC 9 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD MAR PY 2010 VL 22 IS 3 BP 357 EP 365 DI 10.1016/j.cellsig.2009.10.002 PG 9 WC Cell Biology SC Cell Biology GA 548CD UT WOS:000273935700003 PM 19843478 ER PT J AU Restrepo, MI Mortensen, EM Rello, J Brody, J Anzueto, A AF Restrepo, Marcos I. Mortensen, Eric M. Rello, Jordi Brody, Jennifer Anzueto, Antonio TI Late Admission to the ICU in Patients With Community-Acquired Pneumonia Is Associated With Higher Mortality SO CHEST LA English DT Article ID INTENSIVE-CARE-UNIT; PREDICTION RULE; PNEUMOCOCCAL PNEUMONIA; ANTIMICROBIAL THERAPY; SEVERITY; VALIDATION; EPIDEMIOLOGY; PROGNOSIS; GUIDELINES; MANAGEMENT AB Background: Limited data are available on the impact of time to ICU admission and outcomes for patients with severe community acquired pneumonia (CAP). Our objective was to examine the association of time to ICU admission and 30-day mortality in patients with severe CAP. Methods: A retrospective cohort study of 161 ICU subjects with CAP (by International Classification of Diseases, 9th edition, codes) was conducted over a 3-year period at two tertiary teaching hospitals. Timing of the ICU admission was dichotomized into early ICU admission (EICUA, direct admission or within 24 h) and late ICU admission (LICUA, >= day 2). A multivariable analysis using Cox proportional hazard model was created with the primary outcome of 30-day mortality (dependent measure) and the American Thoracic Society (ATS) severity adjustment criteria and time to ICU admission as the independent measures. Results: Eighty-eight percent (n = 142) were EICUA patients compared with 12% (n = 19) LICUA patients. Groups were similar with respect to age, gender, comorbidities, clinical parameters, CAP-related process of care measures, and need for mechanical ventilation. LICUA patients had lower rates of ATS severity criteria at presentation (26.3% vs 53.5%; P = .03). LICUA patients (47.4%) had a higher 30-day mortality compared with EICUA (23.2%) patients (P = .02), which remained after adjusting in tire multivariable analysis (hazard ratio 2.6; 95% Cl, 1.2-5.5; P = .02). Conclusion: Patients with severe CAP with a late ICU admission have increased 30-day mortality after adjustment for illness severity. Further research should evaluate the risk factors associated and their impact on clinical outcomes in patients admitted late to the ICU. CHEST 2010; 137(3):552-557 C1 [Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, ALMD, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX 78229 USA. [Restrepo, Marcos I.; Mortensen, Eric M.; Anzueto, Antonio] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Gen Med, San Antonio, TX 78229 USA. [Restrepo, Marcos I.; Brody, Jennifer; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. [Rello, Jordi] Hosp Univ Tarragona Joan XXIII, Serv Med Intens, Tarragona, Spain. [Rello, Jordi] CIBERES, Tarragona, Spain. [Rello, Jordi] Univ Rovira & Virgili, Tarragona, Spain. RP Restrepo, MI (reprint author), S Texas Vet Hlth Care Syst, ALMD, Vet Evidence Based Res Disseminat & Implementat C, 11C6,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Rello, Jordi/0000-0003-0676-6210; Mortensen, Eric/0000-0002-3880-5563 FU GlaxoSmithKline; Pfizer; Lilly Pharma FX The authors have reported to CHEST the following conflicts of interest: Dr. Restrepo has served on the speakers bureaus of Ortho-McNeil-Janssen, Johnson & Johnson, Pfizer, Covidien, and BAR D, Inc., and on the advisory boards for Ortho-McNeil-Janssen and Johnson & Johnson. Dr Anzueto has served on the speakers bureaus of Pfizer, Boehringer Ingelheim, GlaxoSmithKline, Astra Zeneca, Ortho-McNeil-Janssen, Johnson & Johnson, Bayer-Schering Pharma, and Schering-Plough; on the advisory board of GlaxoSmithKline, Boehringer Ingelheim, Bayer Schering Pharma, Schering-Plough, and Pfizer; and is the principal investigator on research grants that were awarded to the University of Texas Health Science Center at San Antonio by GlaxoSmithKline, Pfizer and Lilly Pharma. Drs Mortensen, Rello, and Brody have reported no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 28 TC 67 Z9 74 U1 0 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2010 VL 137 IS 3 BP 552 EP 557 DI 10.1378/chest.09-1547 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 567WC UT WOS:000275477100010 PM 19880910 ER PT J AU MacDonald, SM Yock, TI AF MacDonald, Shannon M. Yock, Torunn I. TI Proton beam therapy following resection for childhood ependymoma SO CHILDS NERVOUS SYSTEM LA English DT Review DE Ependymoma; Pediatric CNS tumors; Proton radiation; Radiation therapy ID INTENSITY-MODULATED RADIOTHERAPY; CONFORMAL RADIATION-THERAPY; INTRACRANIAL EPENDYMOMAS; PROGNOSTIC-FACTORS; PEDIATRIC-PATIENTS; BRAIN-TUMORS; CRANIOSPINAL IRRADIATION; ADJUVANT CHEMOTHERAPY; LOCALIZED EPENDYMOMA; CURRENT MANAGEMENT AB Proton radiation therapy is a form of radiation with physical properties that can provide an advantage in normal tissue sparing compared to the more commonly used photon therapy. The greatest benefit may be for young patients with tumors requiring relatively high doses of radiation and adjacent to critical structures. Children with central nervous system ependymomas meet these criteria and have a very high likelihood of benefit from proton radiation. At present, proton radiation is limited to select centers. However, knowledge of many of the physical advantages of proton therapy has spread rapidly over the past several years, and its availability is becoming more widespread. C1 [MacDonald, Shannon M.; Yock, Torunn I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [MacDonald, Shannon M.; Yock, Torunn I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP MacDonald, SM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 340,100 Blossom St, Boston, MA 02114 USA. EM smacdonald@partners.org NR 41 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0256-7040 J9 CHILD NERV SYST JI Childs Nerv. Syst. PD MAR PY 2010 VL 26 IS 3 BP 285 EP 291 DI 10.1007/s00381-009-1059-4 PG 7 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 555HW UT WOS:000274500800004 PM 20024657 ER PT J AU Thibault, HB Kurtz, B Raher, MJ Shaik, RS Waxman, A Derumeaux, G Halpern, EF Bloch, KD Scherrer-Crosbie, M AF Thibault, Helene B. Kurtz, Baptiste Raher, Michael J. Shaik, Rahamthulla S. Waxman, Aaron Derumeaux, Genevieve Halpern, Elkan F. Bloch, Kenneth D. Scherrer-Crosbie, Marielle TI Noninvasive Assessment of Murine Pulmonary Arterial Pressure Validation and Application to Models of Pulmonary Hypertension SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE echocardiography; right ventricular systolic pressure; mice ID PULSED DOPPLER ECHOCARDIOGRAPHY; INHALED NITRIC-OXIDE; OF-CARDIOLOGY; TASK-FORCE; PREDICTION; INTERVALS; DISEASE; INJURY; TIME AB Background-Genetically modified mice offer the unique opportunity to gain insight into the pathophysiology of pulmonary arterial hypertension. In mice, right heart catheterization is the only available technique to measure right ventricular systolic pressure (RVSP). However, it is a terminal procedure and does not allow for serial measurements. Our objective was to validate a noninvasive technique to assess RVSP in mice. Methods and Results-Right ventricle catheterization and echocardiography (30-MHz transducer) were simultaneously performed in mice with pulmonary hypertension induced acutely by infusion of a thromboxane analogue, U-46619, or chronically by lung-specific overexpression of interleukin-6. Pulmonary acceleration time (PAT) and ejection time (ET) were measured in the parasternal short-axis view by pulsed-wave Doppler of pulmonary artery flow. Infusion of U-46619 acutely increased RVSP, shortened PAT, and decreased PAT/ET. The pulmonary flow pattern changed from symmetrical at baseline to asymmetrical at higher RVSPs. In wild-type and interleukin-6-overexpressing mice, the PAT correlated linearly with RVSP (r(2) = -0.67, P < 0.0001), as did PAT/ET (r(2) = -0.76, P < 0.0001). Sensitivity and specificity for detecting high RVSP (>32 mm Hg) were 100% (7/7) and 86% (6/7), respectively, for both indices (cutoff values: PAT, <21 ms; PAT/ET, <39%). Intraobserver and interobserver variability of PAT and PAT/ET were <6%. Conclusions-Right ventricular systolic pressure can be estimated noninvasively in mice. Echocardiography is able to detect acute and chronic increases in RVSP with high sensitivity and specificity as well as to assess the effects of treatment on RVSP. This noninvasive technique may permit the characterization of the evolution of pulmonary arterial hypertension in genetically modified mice. (Circ Cardiovasc Imaging. 2010;3:157-163.) C1 [Thibault, Helene B.; Kurtz, Baptiste; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Thibault, Helene B.; Kurtz, Baptiste; Raher, Michael J.; Bloch, Kenneth D.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Raher, Michael J.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Shaik, Rahamthulla S.; Waxman, Aaron] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Pulm Crit Care Unit, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Derumeaux, Genevieve] Univ Lyon 1, INSERM, E 0226, F-69365 Lyon, France. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com FU NIH/NHLBI [1S10RR022586-01A1]; Federation Francaise de Cardiologie; Milton Fund FX This study was supported by a Shared Equipment Grant (NIH/ NHLBI 1S10RR022586-01A1, to Dr Scherrer-Crosbie) as well as by fellowship grants from the Federation Francaise de Cardiologie (to Drs Thibault and Kurtz) and by the Milton Fund (to Dr Scherrer-Crosbie). NR 27 TC 45 Z9 49 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAR PY 2010 VL 3 IS 2 BP 157 EP 163 DI 10.1161/CIRCIMAGING.109.887109 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 570EP UT WOS:000275655100006 PM 20044514 ER PT J AU Deo, R Sotoodehnia, N Katz, R Sarnak, MJ Fried, LF Chonchol, M Kestenbaum, B Psaty, BM Siscovick, DS Shlipak, MG AF Deo, Rajat Sotoodehnia, Nona Katz, Ronit Sarnak, Mark J. Fried, Linda F. Chonchol, Michel Kestenbaum, Bryan Psaty, Bruce M. Siscovick, David S. Shlipak, Michael G. TI Cystatin C and Sudden Cardiac Death Risk in the Elderly SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE cystatin C; kidney; sudden cardiac death; epidemiology ID CHRONIC KIDNEY-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; CORONARY-HEART-DISEASE; STAGE RENAL-DISEASE; UNITED-STATES; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; SERUM CREATININE; WOMEN; DYSFUNCTION AB Background-Recent studies have demonstrated an association between moderate kidney dysfunction and sudden cardiac death in people with cardiovascular disease. Methods and Results-The study was a longitudinal analysis among 4465 participants from the Cardiovascular Health Study without prevalent cardiovascular disease at baseline. Cystatin C and creatinine were measured from baseline sera. Sudden cardiac death (SCD) was defined as a sudden pulseless condition from a cardiac origin in a previously stable individual that occurred out of the hospital or in the emergency room. The association between cystatin C tertiles and SCD was determined with multivariate Cox proportional hazards. A similar analysis compared SCD incidence across creatinine-based estimated glomerular filtration rate (eGFR) tertiles. Over a median follow-up of 11.2 years, 91 adjudicated SCD events occurred. The annual incidence of SCD events increased across cystatin C tertiles: 10 events per 10 000 person years in tertile 1, 25 events per 10 000 person years in tertile 2, and 32 events per 10 000 person-years in the highest cystatin C tertile. These associations persisted after multivariate adjustment: hazards ratio=2.72; 95% confidence interval, 1.44 to 5.16 in tertile 2 and hazards ratio=2.67; 95% confidence interval, 1.33 to 5.35 in tertile 3. After multivariate adjustment, the rate of SCD also increased in a linear distribution across creatinine-based eGFR tertiles: 15 events per 10 000 person-years in tertile 1, 22 events per 10 000 person-years in tertile 2, and 27 events per 10 000 person-years in tertile 3. No significant associations, however, remained between creatinine-based eGFR and SCD after multivariable adjustment. Conclusions-Impaired kidney function, as measured by cystatin C, has an independent association with SCD risk among elderly persons without clinical cardiovascular disease. (Circ Cardiovasc Qual Outcomes. 2010; 3: 159-164.) C1 [Deo, Rajat] Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Fried, Linda F.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Chonchol, Michel] Univ Colorado, Hlth Sci Ctr, Div Renal Dis & Hypertens, Denver, CO USA. [Kestenbaum, Bryan] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Ctr Hlth Studies, Grp Hlth, Seattle, WA USA. [Shlipak, Michael G.] Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Deo, R (reprint author), Univ Penn, Div Cardiol, 3400 Spruce St,9 Founders Cardiol, Philadelphia, PA 19104 USA. EM Rajat.Deo@uphs.upenn.edu FU National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke [R01 AG027002]; [N01-HC-85079]; [N01-HC-85086]; [N01-HC-35129]; [N01-HC-15103]; [N01-HC-55222]; [N01-HC-75150]; [N01-HC-45133]; [U01 HL080295] FX This study was supported by contract Nos. N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, grant No. U01 HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke and R01 AG027002. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. NR 43 TC 38 Z9 38 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAR PY 2010 VL 3 IS 2 BP 159 EP 164 DI 10.1161/CIRCOUTCOMES.109.875369 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575PT UT WOS:000276080200009 PM 20233980 ER PT J AU Kressin, NR Orner, MB Manze, M Glickman, ME Berlowitz, D AF Kressin, Nancy R. Orner, Michelle B. Manze, Meredith Glickman, Mark E. Berlowitz, Dan TI Understanding Contributors to Racial Disparities in Blood Pressure Control SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE blood pressure; hypertension; race; disparities ID COGNITIVE REPRESENTATION; HYPERTENSION TREATMENT; HEALTH-CARE; BELIEFS; RACE; QUESTIONNAIRE; VALIDATION; MEDICATION; ADHERENCE; AMERICANS AB Background-Racial disparities in blood pressure (BP) control are well documented but poorly understood; prior studies have only included a limited range of potential explanatory factors. We examined a comprehensive set of putative factors related to blood pressure control, including patient clinical and sociodemographic characteristics, beliefs about BP and BP medications, medication adherence, and experiences of discrimination, to determine if the impact of race on BP control remains after accounting for such factors. Methods and Results-We recruited 806 white and black patients with hypertension from an urban safety-net hospital. From a questionnaire administered to patients after their clinic visits, electronic medical record and BP data, we assessed an array of patient factors. We then examined the association of patient factors with BP control by modeling it as a function of the covariates using random-effects logistic regression. Blacks indicated worse medication adherence, more discrimination, and more concerns about high BP and BP medications, compared with whites. After accounting for all factors, race was no longer a significant predictor of BP control. Conclusions-Results suggest that equalizing patients' health beliefs, medication adherence, and experiences with care could ameliorate disparities in BP control. Additional attention must focus on the factors associated with race to identify, and ultimately intervene on, the causes of racial disparities in BP outcomes. (Circ Cardiovasc Qual Outcomes. 2010; 3: 173-180.) C1 [Kressin, Nancy R.; Manze, Meredith] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Kressin, Nancy R.; Orner, Michelle B.; Glickman, Mark E.; Berlowitz, Dan] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Glickman, Mark E.; Berlowitz, Dan] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02118 USA. RP Kressin, NR (reprint author), Boston Univ, Sch Med, Gen Internal Med Sect, 801 Massachusetts Ave,2090, Boston, MA 02118 USA. EM nkressin@bu.edu OI Kressin, Nancy/0000-0003-2767-4286; Glickman, Mark/0000-0003-3993-2801 FU NIH/National Heart, Lung, and Blood Institute [R01 HL072814]; Research Career Scientist award; Health Services Research and Development Service; Department of Veterans Affairs [RCS 02-066-1] FX This study was supported by NIH/National Heart, Lung, and Blood Institute grant R01 HL072814 (Dr Kressin, PI); Dr Kressin is also supported by a Research Career Scientist award (RCS 02-066-1) from the Health Services Research and Development Service, Department of Veterans Affairs. NR 33 TC 37 Z9 38 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAR PY 2010 VL 3 IS 2 BP 173 EP 180 DI 10.1161/CIRCOUTCOMES.109.860841 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575PT UT WOS:000276080200011 PM 20233981 ER PT J AU Felker, GM Pang, PS Adams, KF Cleland, JGF Cotter, G Dickstein, K Filippatos, GS Fonarow, GC Greenberg, BH Hernandez, AF Khan, S Komajda, M Konstam, MA Liu, PP Maggioni, AP Massie, BM McMurray, JJ Mehra, M Metra, M O'Connell, J O'Connor, CM Pina, IL Ponikowski, P Sabbah, HN Teerlink, JR Udelson, JE Yancy, CW Zannad, F Gheorghiade, M AF Felker, G. Michael Pang, Peter S. Adams, Kirkwood F. Cleland, John G. F. Cotter, Gad Dickstein, Kenneth Filippatos, Gerasimos S. Fonarow, Gregg C. Greenberg, Barry H. Hernandez, Adrian F. Khan, Sadiya Komajda, Michel Konstam, Marvin A. Liu, Peter P. Maggioni, Aldo P. Massie, Barry M. McMurray, John J. Mehra, Mandeep Metra, Marco O'Connell, John O'Connor, Christopher M. Pina, Ileana L. Ponikowski, Piotr Sabbah, Hani N. Teerlink, John R. Udelson, James E. Yancy, Clyde W. Zannad, Faiez Gheorghiade, Mihai CA Int AHFS Working Grp TI Clinical Trials of Pharmacological Therapies in Acute Heart Failure Syndromes Lessons Learned and Directions Forward SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; patients; trials; acute heart failure ID WORSENING RENAL-FUNCTION; IN-HOSPITAL MORTALITY; RANDOMIZED CONTROLLED-TRIALS; CARDIAC TROPONIN-I; END-POINTS; MYOCARDIAL-INFARCTION; RISK STRATIFICATION; FLUID ACCUMULATION; PROGNOSTIC VALUE; OUTCOMES C1 [Gheorghiade, Mihai] Northwestern Univ, Ctr Cardiovasc Qual & Outcomes, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [Felker, G. Michael] Duke Clin Res Inst Durham, Durham, NC USA. [Pang, Peter S.] Northwestern Univ, Ctr Cardiovasc Qual & Outcomes, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. [Adams, Kirkwood F.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Adams, Kirkwood F.] Univ N Carolina, Sch Med, Dept Radiol, Chapel Hill, NC 27514 USA. [Cleland, John G. F.] Univ Hull, Dept Cardiol, Castle Hill Hosp, Kingston Upon Hull, Yorks, England. [Cotter, Gad] Momentum Res Inc, Durham, NC USA. Stavanger Univ Hosp, Stavanger, Norway. [Dickstein, Kenneth] Univ Bergen, Inst Internal Med, Bergen, Norway. [Filippatos, Gerasimos S.] Univ Athens, Hosp Attikon, Athens, Greece. [Fonarow, Gregg C.] David Geffen UCLA, Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Greenberg, Barry H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Hernandez, Adrian F.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Komajda, Michel] Univ Paris 06, AP HP, Paris, France. [Konstam, Marvin A.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA. [Konstam, Marvin A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Liu, Peter P.] Univ Toronto, Toronto Gen Hosp, Inst Circulatory & Resp Hlth, Canadian Inst Hlth, Toronto, ON M5S 1A1, Canada. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Massie, Barry M.] Univ Calif San Francisco, Div Cardiol, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [McMurray, John J.] Univ Glasgow, BHF Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Mehra, Mandeep] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Metra, Marco] Univ & Civil Hosp Brescia, Dept Expt & Appl Med, Brescia, Italy. [O'Connell, John] Feinberg Sch Med, Div Cardiol, Chicago, IL USA. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Heart Ctr, Div Clin Pharmacol, Durham, NC 27710 USA. [Pina, Ileana L.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Ponikowski, Piotr] Med Univ, Fac Hlth Sci, Clin Mil Hosp, Katowice, Poland. [Sabbah, Hani N.] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. [Teerlink, John R.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA. [Yancy, Clyde W.] Baylor Heart & Vasc Inst, Dallas, TX USA. [Zannad, Faiez] Nancy Univ, Dept Cardiol, Nancy, France. RP Gheorghiade, M (reprint author), Northwestern Univ, Ctr Cardiovasc Qual & Outcomes, Feinberg Sch Med, Dept Med, 645 N Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu RI Teerlink, John/D-2986-2012; Lainscak, Mitja/F-3237-2015; Ponikowski, Piotr/O-6454-2015; Hernandez, Adrian F./A-7818-2016; OI Ponikowski, Piotr/0000-0002-3391-7064; Mehra, Mandeep/0000-0001-8683-7044; Hernandez, Adrian F./0000-0003-3387-9616; Cleland, John/0000-0002-1471-7016; Metra, Marco/0000-0001-6691-8568; Maggioni, Aldo Pietro/0000-0003-2764-6779; mcmurray, john/0000-0002-6317-3975 NR 69 TC 82 Z9 86 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAR PY 2010 VL 3 IS 2 BP 314 EP 325 DI 10.1161/CIRCHEARTFAILURE.109.893222 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 570EQ UT WOS:000275655400021 PM 20233993 ER PT J AU Dixon, JA Spinale, FG AF Dixon, Jennifer A. Spinale, Francis G. TI Response to Letter Regarding Article "Large Animal Models of Heart Failure: A Critical Link in the Translation of Basic Science to Clinical Practice" SO CIRCULATION-HEART FAILURE LA English DT Letter ID CORONARY MICROEMBOLIZATION; SHEEP C1 [Dixon, Jennifer A.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Dixon, JA (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. EM wilburnm@musc.edu NR 5 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAR PY 2010 VL 3 IS 2 BP E4 EP E4 DI 10.1161/CIRCHEARTFAILURE.109.934430 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 570EQ UT WOS:000275655400027 ER PT J AU Primo, VC Marusic, S Franklin, CC Goldmann, WH Achaval, CG Smith, RN Arnaout, MA Nikolic, B AF Primo, V. C. Marusic, S. Franklin, C. C. Goldmann, W. H. Achaval, C. G. Smith, R. N. Arnaout, M. A. Nikolic, B. TI Anti-PR3 immune responses induce segmental and necrotizing glomerulonephritis SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE animal models/mice/rats; anti-neutrophil cytoplasmic antibodies/anti-PR3/myeloperoxidase; autoimmunity; glomerulonephritis; Wegener's granulomatosis ID ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES; SPONTANEOUS AUTOIMMUNE ENCEPHALOMYELITIS; NEUTROPHIL SERINE PROTEINASE; RECEPTOR TRANSGENIC MICE; T-CELLS INDUCE; WEGENERS-GRANULOMATOSIS; IN-VIVO; RECOMBINANT PROTEINASE-3; ACTIVATED NEUTROPHILS; DISEASE-ACTIVITY AB Wegener's granulomatosis (WG) is a life-threatening autoimmune vasculitis that affects lungs, kidneys and other organs. A hallmark of WG is the presence of classic anti-neutrophil cytoplasmic antibodies (c-ANCA) against self-proteinase 3 (PR3). Little is known about the role of these antibodies and PR3-specific immune responses in disease development. In this study, we demonstrate that PR3-specific autoimmune responses are pathogenic in non-obese diabetic (NOD) mice with an impaired regulatory arm of the immune response. Immunization of autoimmunity prone NOD mice with rmPR3 (recombinant mouse PR3) in complete Freund's adjuvant (CFA) resulted in high levels of c-ANCA, without detectable disease development. However, when splenocytes from these immunized mice were transferred into immunodeficient NOD-severe combined immunodeficiency (SCID) mice, the recipient mice developed vasculitis and severe segmental and necrotizing glomerulonephritis. No disease developed in NOD-SCID mice that received splenocytes from the CFA-alone-immunized donors (controls), indicating that disease development depends upon PR3-specific immune responses. In contrast to the pathology observed in NOD-SCID mice, no disease was observed when splenocytes from rmPR3-immunized C57BL/6 mice were transferred into immunodeficient C57BL/6-RAG-1(-/-) mice, suggesting that complex and probably multi-genetic factors play a role in the regulation of disease development. C1 [Primo, V. C.; Franklin, C. C.; Arnaout, M. A.; Nikolic, B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA USA. [Smith, R. N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Marusic, S.] Hooke Labs Inc, Lawrence, MA USA. [Goldmann, W. H.] Friedrich Alexander Univ Erlangen Nuremberg, Ctr Med Phys & Technol, Erlangen, Germany. [Achaval, C. G.] Nuevo Hosp San Antonio de Padua, Pathol Lab, Rio Cuarto, Argentina. RP Nikolic, B (reprint author), Massachusetts Gen Hosp, Div Nephrol, MGH E,Bldg 149-8000,13th St, Charlestown, MA 02129 USA. EM bnikolic@partners.org RI Goldmann, Wolfgang/H-5572-2013 FU National Kidney Foundation; NIH/NIDDK [R03 DK067940]; DAAD, BaCaTec, BFHZ FX This work was supported in part by the Patricia Welder Robinson Young Investigator Grant of the National Kidney Foundation (B. N.), by the NIH/NIDDK R03 DK067940 (B. N.) and by DAAD, BaCaTec, BFHZ (W. H. G.). We thank Dr Takashi Sugimori for providing us with mouse PR3 cDNA clone. NR 43 TC 39 Z9 41 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAR PY 2010 VL 159 IS 3 BP 327 EP 337 DI 10.1111/j.1365-2249.2009.04072.x PG 11 WC Immunology SC Immunology GA 544VG UT WOS:000273686800010 PM 20015271 ER PT J AU Castelino, FV Brooks, SF Funke, M Chun, J Luster, AD Tager, AM AF Castelino, F. V. Brooks, S. F. Funke, M. Chun, J. Luster, A. D. Tager, A. M. TI LOSS OF LPA1 SIGNALING PROTECTS AGAINST DERMAL FIBROSIS IN A BLEOMYCIN-INDUCED MOUSE MODEL OF SYSTEMIC SCLEROSIS SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Castelino, F. V.; Brooks, S. F.; Funke, M.; Luster, A. D.; Tager, A. M.] Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02115 USA. [Brooks, S. F.; Luster, A. D.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Tager, A. M.] Pulm & Crit Care Unit, Boston, MA USA. [Chun, J.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2010 VL 28 IS 2 SU 58 BP S106 EP S107 PG 2 WC Rheumatology SC Rheumatology GA 616IT UT WOS:000279203200130 ER PT J AU Mino-Kenudson, M Chirieac, LR Law, K Hornick, JL Lindeman, N Mark, EJ Cohen, DW Johnson, BE Janne, PA Iafrate, AJ Rodig, SJ AF Mino-Kenudson, Mari Chirieac, Lucian R. Law, Kenny Hornick, Jason L. Lindeman, Neal Mark, Eugene J. Cohen, David W. Johnson, Bruce E. Jaenne, Pasi A. Iafrate, A. John Rodig, Scott J. TI A Novel, Highly Sensitive Antibody Allows for the Routine Detection of ALK-Rearranged Lung Adenocarcinomas by Standard Immunohistochemistry SO CLINICAL CANCER RESEARCH LA English DT Article ID EML4-ALK FUSION GENE; LARGE-CELL LYMPHOMA; CLINICAL-FEATURES; CANCER; MUTATIONS; GEFITINIB; SPECTRUM; TISSUES; T(2/5); SYSTEM AB Purpose: Approximately 5% of lung adenocarcinomas harbor an EML4-ALK gene fusion and define a unique tumor group that may be responsive to targeted therapy. However ALK-rearranged lung adenocarcinomas are difficult to detect by either standard fluorescence in situ hybridization or immunohistochemistry (IHC) assays. In the present study, we used novel antibodies to compare ALK protein expression in genetically defined lung cancers and anaplastic large cell lymphomas. Experimental Design: We analyzed 174 tumors with one standard and two novel monoclonal antibodies recognizing the ALK protein. Immunostained tissue sections were assessed for the level of tumor-specific ALK expression by objective quantitative image analysis and independently by three pathologists. Results: ALK protein is invariably and exclusively expressed in ALK-rearranged lung adenocarcinomas but at much lower levels than in the prototypic ALK-rearranged tumor, anaplastic large cell lymphoma, and as a result, is often not detected by conventional IHC. We further validate a novel IHC that shows excellent sensitivity and specificity (100% and 99%, respectively) for the detection of ALK-rearranged lung adenocarcinomas in biopsy specimens, with excellent interobserver agreement between pathologists (kappa statistic, 0.94). Conclusions: Low levels of ALK protein expression is a characteristic feature of ALK-rearranged lung adenocarcinomas. However, a novel, highly sensitive IHC assay reliably detects lung adenocarcinomas with ALK rearrangements and obviates the need for fluorescence in situ hybridization analysis for the majority of cases, and therefore could be routinely applicable in clinical practice to detect lung cancers that may be responsive to ALK inhibitors. Clin Cancer Res; 16(5); 1561-71. (C)2010 AACR. C1 [Mino-Kenudson, Mari; Mark, Eugene J.; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chirieac, Lucian R.; Law, Kenny; Hornick, Jason L.; Lindeman, Neal; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Cohen, David W.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Johnson, Bruce E.; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 15 Fruit St, Boston, MA 02114 USA. EM srodig@partners.org FU National Cancer Institute [CA090578]; Department of Defense [W81XWH06-1- 0303]; NIH [R01CA136851] FX Grant Support; National Cancer Institute Specialized Programs of Research Excellence in Lung Cancer grant CA090578, Department of Defense grant W81XWH06-1- 0303, and NIH grant R01CA136851 (P. A. Janne and B. E. Johnson). NR 32 TC 246 Z9 267 U1 3 U2 19 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 MAR 1 PY 2010 VL 16 IS 5 BP 1561 EP 1571 DI 10.1158/1078-0432.CCR-09-2845 PG 11 WC Oncology SC Oncology GA 607ZJ UT WOS:000278545500023 PM 20179225 ER PT J AU Ofran, Y Kim, HT Brusic, V Blake, L Mandrell, M Wu, CJ Sarantopoulos, S Bellucci, R Keskin, DB Soiffer, RJ Antin, JH Ritz, J AF Ofran, Yishai Kim, Haesook T. Brusic, Vladimir Blake, Loren Mandrell, Michael Wu, Catherine J. Sarantopoulos, Stefanie Bellucci, Roberto Keskin, Derin B. Soiffer, Robert J. Antin, Joseph H. Ritz, Jerome TI Diverse Patterns of T-Cell Response against Multiple Newly Identified Human Y Chromosome-Encoded Minor Histocompatibility Epitopes SO CLINICAL CANCER RESEARCH LA English DT Article ID VERSUS-HOST-DISEASE; H-Y; GRAFT-REJECTION; FEMALE DONORS; GENE CODES; B-CELL; ANTIGEN; TRANSPLANTATION; HLA; RECOGNITION AB Purpose: Donor T cells respond to minor histocompatibility antigens (mHA), resulting in both graft-versus-host disease and graft versus leukemia after allogeneic hematopoietic stem cell transplantation. Because relatively few mHAs are known, we developed a new approach to predict and subsequently validate candidate mHA. Experimental Design: We developed an algorithm based on genetic disparities between Y chromosome-encoded and X chromosome-encoded proteins and known requirements for binding to HLA class I molecules to predict Y chromosome-derived, HLA A*0201-restricted peptides (HY) and ranked peptides based on potential immunogenicity. We evaluated T-cell responses to 41 candidate peptides in 28 male recipients with female donors (FM), 22 male recipients with male donors (MM), and 26 normal individuals. All patients and donors were HLA A*0201 positive. Results: Thirteen peptides derived from five proteins elicited significantly greater T-cell responses in FM patients compared with MM patients and in normal females compared with normal males. Six peptides were more immunogenic than the only previously known HLA A*0201-restricted Y-encoded mHA. Twenty-seven of 28 FM patients responded to at least one HY peptide, but despite a common Y chromosome mismatch and expression of HLA A*0201, each patient responded to a unique set of peptides. Conclusions: Novel HLA A*0201-restricted HY epitopes can be predicted and validated in patients after allogeneic hematopoietic stem cell transplantation. Highly diverse patterns of T-cell response against these epitopes have been identified. Prospective monitoring of responses to large panels of immunogenic peptides can facilitate the identification of clinically relevant targets of graft-versus-host disease and graft versus leukemia. Clin Cancer Res; 16(5); 1642-51. (C) 2010 AACR. C1 [Ofran, Yishai; Blake, Loren; Mandrell, Michael; Wu, Catherine J.; Sarantopoulos, Stefanie; Bellucci, Roberto; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Ofran, Yishai; Brusic, Vladimir; Wu, Catherine J.; Keskin, Derin B.; Ritz, Jerome] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ritz, Jerome] Harvard Stem Cell Inst, Boston, MA USA. [Ofran, Yishai; Wu, Catherine J.; Ritz, Jerome] Harvard Univ, Sch Med, Boston, MA USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM Jerome_Ritz@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU NIH [CA142106, AI29530]; Ted and Eileen Pasquarello Research Fund; American Physicians Fellowship for Medicine in Israel FX Grant Support; NIH grants CA142106 and AI29530, Ted and Eileen Pasquarello Research Fund, and American Physicians Fellowship for Medicine in Israel. NR 42 TC 18 Z9 18 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2010 VL 16 IS 5 BP 1642 EP 1651 DI 10.1158/1078-0432.CCR-09-2701 PG 10 WC Oncology SC Oncology GA 607ZJ UT WOS:000278545500032 PM 20160060 ER PT J AU Shen, YP Wu, BL Gusella, JF AF Shen, Yiping Wu, Bai-Lin Gusella, James F. TI Large-Scale Medical Resequencing for X-Linked Mental Retardation SO CLINICAL CHEMISTRY LA English DT Article C1 [Gusella, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Shen, Yiping; Wu, Bai-Lin] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Shen, Yiping] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Wu, Bai-Lin] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Gusella, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2010 VL 56 IS 3 BP 339 EP 341 DI 10.1373/clinchem.2009.135020 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 566RZ UT WOS:000275392000004 PM 20040618 ER PT J AU Kalra, MK Francis, IR AF Kalra, Mannudeep K. Francis, Isaac R. TI Personalized Dose Reduction for Computed Tomography Scanning: Size Matters, so Does Prior Radiation Exposures SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID CYSTIC-FIBROSIS; CT; APPENDICITIS; OPTIMIZATION; CHILDREN C1 [Kalra, Mannudeep K.] Massachusetts Gen Hosp, Massachusetts Gen Hosp Imaging, Boston, MA 02114 USA. [Francis, Isaac R.] Univ Michigan Hosp, Dept Radiol, Ann Arbor, MI 48109 USA. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Hosp Imaging, Boston, MA 02114 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2010 VL 8 IS 3 BP 231 EP 232 DI 10.1016/j.cgh.2009.12.001 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 592ZR UT WOS:000277421200006 PM 20005984 ER PT J AU Robbins, GK Johnson, KL Chang, YC Jackson, KE Sax, PE Meigs, JB Freedberg, KA AF Robbins, Gregory K. Johnson, Kristin L. Chang, Yuchiao Jackson, Katherine E. Sax, Paul E. Meigs, James B. Freedberg, Kenneth A. TI Predicting Virologic Failure in an HIV Clinic SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL LOAD; HIV-1-INFECTED PATIENTS; COLLABORATIVE ANALYSIS; DISEASE PROGRESSION; RISK-FACTORS; INFECTION; WOMEN; VALIDATION AB Background. We sought to use data captured in the electronic health record (EHR) to develop and validate a prediction rule for virologic failure among patients being treated for infection with human immunodeficiency virus (HIV). Methods. We used EHRs at 2 Boston tertiary care hospitals, Massachusetts General Hospital and Brigham and Women's Hospital, to identify HIV-infected patients who were virologically suppressed (HIV RNA level <= 400 copies/mL) on antiretroviral therapy (ART) during the period from 1 January 2005 through 31 December 2006. We used a multivariable logistic model with data from Massachusetts General Hospital to derive a 1-year virologic failure prediction rule. The model was validated using data from Brigham and Women's Hospital. We then simplified the scoring scheme to develop a clinical prediction rule. Results. The 1-year virologic failure prediction model, using data from 712 patients from Massachusetts General Hospital, demonstrated good discrimination (C statistic, 0.78) and calibration (chi(2) = 6.6 P = .58). The validation model, based on 362 patients from Brigham and Women's Hospital, also showed good discrimination (C statistic, 0.79) and calibration (chi 2 = 1.9; P = .93). The clinical prediction rule included 7 predictors (suboptimal adherence, CD4 cell count <100 cells/mu L, drug and/or alcohol abuse, highly ART experienced, missed >= 1 appointment, prior virologic failure, and suppressed <= 12 months) and appropriately stratified patients in the validation data set into low-, medium-, and high-risk groups, with 1-year virologic failure rates of 3.0%, 13.0%, and 28.6%, respectively. Conclusions. A risk score based on 7 variables available in the EHR predicts HIV virologic failure at 1 year and could be used for targeted interventions to improve outcomes in HIV infection. C1 [Robbins, Gregory K.] Massachusetts Gen Hosp, Div Infect Dis, Infect Dis Associates, Boston, MA 02114 USA. [Chang, Yuchiao; Meigs, James B.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Sax, Paul E.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Robbins, Gregory K.; Johnson, Kristin L.; Chang, Yuchiao; Sax, Paul E.; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. [Robbins, Gregory K.; Chang, Yuchiao; Sax, Paul E.; Meigs, James B.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Robbins, GK (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Infect Dis Associates, 55 Fruit St,Cox 506, Boston, MA 02114 USA. EM grobbins@partners.org RI Robbins, Gregory/F-7988-2011 FU Massachusetts General Hospital [K01AI062435, K24AI062476, P30AI42851, K24DK080140, R37AI42006] FX Grants K01AI062435 (to G. K. R.), K24AI062476 (to K. A. F.), P30AI42851 (to G. K. R. and K. A. F.), K24DK080140 (to J.B.M.), and R37AI42006 (to K. A. F.); Massachusetts General Hospital Clinical Research Program. NR 40 TC 29 Z9 29 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 1 PY 2010 VL 50 IS 5 BP 779 EP 786 DI 10.1086/650537 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 552XV UT WOS:000274329400022 PM 20121574 ER PT J AU Treger, R Pirouz, S Kamangar, N Corry, D AF Treger, Richard Pirouz, Shahriar Kamangar, Nader Corry, Dalila TI Agreement between Central Venous and Arterial Blood Gas Measurements in the Intensive Care Unit SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID DIABETIC-KETOACIDOSIS; VALUES; PH; BICARBONATE; PREDICTION; FAILURE; DISEASE; PCO(2) AB Background and objectives: Venous blood gas (VBG) analysis is a safer procedure than arterial blood gas (ABC) analysis and may be an alternative for determining acid-base status. The objective of this study was to examine the agreement between ABC and central VBG samples for all commonly used parameters in a medical intensive care unit (ICU) population. Design, setting, participants, & measurements: We performed a single-center, prospective trial to assess the agreement between arterial and central VBG measurements in a medical ICU. Adult patients who were admitted to the ICU and required both a central venous line and an arterial line were enrolled. When an ABC was performed, a central venous sample was obtained to examine the agreement among the pH, PCO(2), and bicarbonate. Data comparing central and peripheral VBG values were also obtained. Results: The mean arterial minus venous difference for pH, PCO(2), and bicarbonate was 0.027, -3.8, and -0.80, respectively. Bland-Altman plots for agreement of pH, PCO(2), and bicarbonate showed 95% limits of agreement of -0.028 to 0.081, -1.2.3 to 4.8, and -4.0 to 2.4, respectively. Regression equations were derived to predict arterial values from venous values as follows: Arterial pH = -0.307 + 1.05 x venous pH, arterial PCO(2) = 0.805 + 0.936 x venous PCO(2), and arterial bicarbonate = 0.513 + 0.945 x venous bicarbonate. The mean central minus peripheral differences for pH, PCO(2), and bicarbonate were not clinically important. Conclusions: Peripheral or central venous PH, PCO(2), and bicarbonate can replace their arterial equivalents in many clinical contexts encountered in the ICU. C1 [Treger, Richard] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Nephrol, Los Angeles, CA USA. [Treger, Richard] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Emergency Med, Los Angeles, CA USA. [Corry, Dalila] Olive View UCLA Med Ctr, Dept Nephrol, Sylmar, CA 91342 USA. [Pirouz, Shahriar] Olive View UCLA Med Ctr, Dept Internal Med, Sylmar, CA 91342 USA. [Kamangar, Nader] Olive View UCLA Med Ctr, Dept Pulm Crit Care, Sylmar, CA 91342 USA. [Treger, Richard; Pirouz, Shahriar; Kamangar, Nader; Corry, Dalila] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Treger, R (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,W111A, Los Angeles, CA 90073 USA. EM richard.treger@va.gov FU Olive-View-UCLA Education and Research Institute FX This project was supported by a seed grant from the Olive-View-UCLA Education and Research Institute. NR 16 TC 23 Z9 26 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2010 VL 5 IS 3 BP 390 EP 394 DI 10.2215/CJN.00330109 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 565WB UT WOS:000275325000002 PM 20019117 ER PT J AU Bhan, I Burnett-Bowie, SAM Ye, J Tonelli, M Thadhani, R AF Bhan, Ishir Burnett-Bowie, Sherri-Ann M. Ye, Jun Tonelli, Marcello Thadhani, Ravi TI Clinical Measures Identify Vitamin D Deficiency in Dialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; ARTIFICIAL NEURAL-NETWORKS; REGRESSION TREE ANALYSIS; HEMODIALYSIS-PATIENTS; 25-HYDROXYVITAMIN D; LOGISTIC-REGRESSION; IMPROVED SURVIVAL; D INSUFFICIENCY; RENAL-DISEASE; MORTALITY AB Background and objectives: Vitamin D deficiency (defined by serum levels of 25-hydroxyvitamin D) is common in patients with ESRD on hemodialysis, but risk factors are unknown. This study was conducted to determine whether routinely measured clinical and demographic parameters could identify dialysis patients who are vitamin D deficient. Design, setting, participants, & measurements: Nine-hundred eight patients with 25-hydroxyvitamin D levels were identified from the Accelerated Mortality on Renal Replacement (ArMORR) cohort of incident U.S. dialysis patients and were divided into training (60%) and validation (40%) sets. Predictive models were generated from routinely assessed clinical and demographic data in the training set using logistic regression modeling, neural networks, and decision trees with vitamin D deficiency as the dependent variable. Models underwent progressive variable reduction to identify the simplest model that remained predictive. Results: Seventy-nine percent of the population was vitamin D deficient (25-hydroxyvitamin D <30 ng/ml). Black race, female sex, winter season, and hypoalbuminemia (serum albumin <= 3.1 g/dl) were the strongest predictors of vitamin D deficiency. In the validation set, the presence of hypoalbuminemia and winter season increased the likelihood of vitamin D deficiency in black women (from 90% to 100%), black men (from 85% to 100%), white women (from 82% to 94%), and white men (from 66% to 92%). Conclusions: Deficiency of 25-hydroxyvitamin D is nearly universal among patients with hypoalbuminemia initiating chronic hemodialysis in winter. C1 [Bhan, Ishir; Ye, Jun; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Bhan, Ishir] Massachusetts Gen Hosp, Dept Med, Comp Sci Lab, Boston, MA 02114 USA. [Burnett-Bowie, Sherri-Ann M.] Massachusetts Gen Hosp, Dept Med, Div Endocrinol, Boston, MA 02114 USA. [Tonelli, Marcello] Univ Alberta, Dept Med, Div Nephrol, Edmonton, AB, Canada. RP Bhan, I (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, 50 Staniford St,Suite 750, Boston, MA 02114 USA. EM ibhan@partners.org RI Tonelli, Marcello/B-3028-2009; OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU National Kidney Foundation; National Institutes of Health [1K23DK081677] FX I.B. received support from a National Kidney Foundation Young Investigator Grant and from National Institutes of Health grant 1K23DK081677. NR 51 TC 42 Z9 43 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2010 VL 5 IS 3 BP 460 EP 467 DI 10.2215/CJN.06440909 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 565WB UT WOS:000275325000012 PM 20185603 ER PT J AU Robinson, ES Matulonis, UA Ivy, P Berlin, ST Tyburski, K Penson, RT Humphreys, BD AF Robinson, Emily S. Matulonis, Ursula A. Ivy, Percy Berlin, Suzanne T. Tyburski, Karin Penson, Richard T. Humphreys, Benjamin D. TI Rapid Development of Hypertension and Proteinuria with Cediranib, an Oral Vascular Endothelial Growth Factor Receptor Inhibitor SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; BLOOD-PRESSURE; ANGIOGENESIS INHIBITOR; BREAST-CANCER; BEVACIZUMAB; TRIAL; EXPRESSION; PACLITAXEL; REGRESSION; SORAFENIB AB Background and objectives: Hypertension and proteinuria are common but poorly understood renal toxicities of vascular endothelial growth factor (VEGF) receptor signaling pathway inhibitors. In this phase II study of cediranib (AZD2171) for recurrent epithelial ovarian cancer, the time course and severity of BP changes and proteinuria were characterized. Design, setting, participants, & measurements: 46 women ages 41 to 77 years were treated with cediranib. 26% had baseline hypertension. Twice-daily BP was recorded. Urinalyses were performed every 2 weeks, and in some patients proteinuria was further quantified. Results: 31 women (67%) developed hypertension by day 3; 87% by the end of the study. 43%, developed grade >= 3 hypertension. Mean systolic BP increase over 3 days was 18 mmHg. Women above the mean age (>= 57 years) had a larger rise in systolic BP by day 3 (15.9 versus 7.0 mmHg). 14 women developed proteinuria. There was a dose response (45 versus 30 mg daily). Proteinuria also developed rapidly, with 7 of 14 women developing proteinuria within 2 weeks. Only 7 of 20 women who developed grade 3 hypertension developed proteinuria. Conclusions: Cediranib induced a rapid but variable rise in BP within 3 days of initiation in most patients. Proteinuria was common and also developed rapidly. The rapid development of hypertension suggests that acute inhibition of VEGF-dependent vasodilation might explain the BP rise with VEGF inhibitors. Clinicians must be vigilant in early detection and management of toxicities of this expanding drug class, especially in older patients. Clin J Am Soc Nephrol 5: 477-483, 2010. doi: 10.2215/CJN.08111109 C1 [Robinson, Emily S.; Humphreys, Benjamin D.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. [Matulonis, Ursula A.; Berlin, Suzanne T.; Tyburski, Karin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Humphreys, Benjamin D.] Dana Farber Canc Inst, Adult Survivorship Program, Boston, MA 02115 USA. [Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Penson, Richard T.] Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. RP Robinson, ES (reprint author), Channing Labs, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. EM Erobinson11@partners.org; bhumphreys@partners.org FU National Kidney Foundation; Madeline Franchi Ovarian Cancer Fund; Ovations for the Cure; National Institutes of Health [DK073628, UL1 RR 025758-02] FX Support for this research was provided by a National Kidney Foundation Fellowship Grant (to E.S.R.), The Madeline Franchi Ovarian Cancer Fund, Ovations for the Cure, National Institutes of Health grant DK073628 (to B.D.H.), and a pilot grant from Harvard Catalyst: National Institutes of Health grant UL1 RR 025758-02 with financial contributions from participating institutions (to B.D.H.). NR 34 TC 36 Z9 38 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2010 VL 5 IS 3 BP 477 EP 483 DI 10.2215/CJN.08111109 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 565WB UT WOS:000275325000014 PM 20056761 ER PT J AU Al-Shahrouri, HZ Ramirez, P Fanti, P Abboud, H Lorenzo, C Haffner, S AF Al-Shahrouri, H. Z. Ramirez, P. Fanti, P. Abboud, H. Lorenzo, C. Haffner, S. TI NMR identifies atherogenic lipoprotein abnormalities in early diabetic nephropathy that are unrecognized by conventional analysis SO CLINICAL NEPHROLOGY LA English DT Article DE diabetic nephropathy; atherogenic lipids; albuminuria ID CHRONIC KIDNEY-DISEASE; NUCLEAR-MAGNETIC-RESONANCE; INSULIN-RESISTANCE ATHEROSCLEROSIS; FATAL MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; DENSITY LIPOPROTEINS; APOLIPOPROTEIN-B; PARTICLE-SIZE; A-I; RISK AB Lipoprotein abnormalities are likely contributors to the high risk of cardiovascular disease in the chronic kidney disease (CKD) population, although information is limited. Specifically, little is known about lipoprotein abnormalities during the early stages of diabetic kidney disease. The aim of this study was to investigate the relationship between lipoproteins and early manifestations of CKD in the 517 Type 2 diabetes mellitus (T2DM) patients who participated in the Insulin Resistance Atherosclerosis Study ( IRAS). Methods: Lipoprotein abnormalities were measured by conventional lipid analysis, nuclear magnetic resonance (NMR) spectroscopy, gel gradient electrophoresis (GE), immunoprecipitation (IP), and ELISA. We grouped the cases into albumin to creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) quartiles. Results: In the conventional lipid analysis, triglycerides (TG) correlated directly with ACR and inversely with eGFR quartiles (p = 0.01), while LDL, HDL cholesterol did not correlate with change in ACR or eGFR. ACR was directly associated with apoB, total VLDL, medium VLDL, IDL and small LDL particle concentrations (p <= 0.03), and inversely with large LDL particles (p = 0.01) and LDL size (p = 0.008). Estimated GFR quartiles were inversely associated with total VLDL, small VLDL, IDL, and medium HDL particles (p <= 0.01). Conclusion: In subjects with T2DM, mild albuminuria and reduction in eGFR were associated with numerous atherogenic lipoprotein abnormalities that were detected by the combination of NMR spectroscopy, gel gradient electrophoresis, immunoprecipitation and ELISA but not by the standard clinical lipid analysis. C1 [Al-Shahrouri, H. Z.; Ramirez, P.; Fanti, P.; Abboud, H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Nephrol, San Antonio, TX 78229 USA. [Lorenzo, C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. [Haffner, S.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Al-Shahrouri, HZ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM alshahrouri@uthscsa.edu FU National Heart, Lung, and Blood Institute [HL-47887, HL-47889, HL-47890, HL-47892, HL-47902]; NCRR GCRC [M01 RR431, M01 RR01346] FX This work was supported by National Heart, Lung, and Blood Institute Grants HL-47887, HL-47889, HL-47890, HL-47892, HL-47902 and the General Clinical Research Centers Program (NCRR GCRC, M01 RR431, M01 RR01346). NR 37 TC 5 Z9 5 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD MAR PY 2010 VL 73 IS 3 BP 180 EP 189 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 563KM UT WOS:000275130800002 PM 20178716 ER PT J AU Locke, C Mceuen, J Felder, R Radcliffe, L Barrett, T Stevens, B Lesselroth, B Pope, D AF Locke, Christy Mceuen, Judy Felder, Robert Radcliffe, Leann Barrett, Thomas Stevens, Brent Lesselroth, Blake Pope, Diana TI Adherence, Safety, and Effectiveness of a Paper Versus Electronic Insulin Infusion Protocol in Acute Care SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Locke, Christy; Mceuen, Judy; Felder, Robert; Radcliffe, Leann; Barrett, Thomas; Stevens, Brent; Lesselroth, Blake; Pope, Diana] Portland VA Med Ctr, Portland, OR 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2010 VL 24 IS 2 BP 88 EP 89 PG 2 WC Nursing SC Nursing GA 570QP UT WOS:000275693300014 ER PT J AU Richardson, J Tjoelker, R AF Richardson, Jenny Tjoelker, Rita TI Beyond the Bundle: The Value of the Clinical Nurse Specialists in Continuing Evidence-Based Practice Changes SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Richardson, Jenny; Tjoelker, Rita] Portland VA Med Ctr, Portland, OR 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2010 VL 24 IS 2 BP 89 EP 89 PG 1 WC Nursing SC Nursing GA 570QP UT WOS:000275693300017 ER PT J AU Busch, AH Brenk, T AF Busch, Ann Herbage Brenk, Thomas TI Clinical Nurse Specialist Influencing Local to National Systems: Electronic Transplant Referral SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Busch, Ann Herbage; Brenk, Thomas] Portland VA Med Ctr, Portland, OR 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2010 VL 24 IS 2 BP 91 EP 91 PG 1 WC Nursing SC Nursing GA 570QP UT WOS:000275693300023 ER PT J AU Valdez, CR Richardson, J Schrader, J AF Valdez, Christine R. Richardson, Jenny Schrader, Jennifer TI Evaluation of an Interdisciplinary Educational Program SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Valdez, Christine R.; Richardson, Jenny; Schrader, Jennifer] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2010 VL 24 IS 2 BP 95 EP 95 PG 1 WC Nursing SC Nursing GA 570QP UT WOS:000275693300035 ER PT J AU Atherton, S Busch, A Church, V Cole, JA Halmquist, J Locke, C Patten, S Richardson, J Tjoelker, R Valdez, C Vogeley, C AF Atherton, Sherri Busch, Ann Church, Victoria Cole, June Ann Halmquist, Jennifer Locke, Christy Patten, Stephen Richardson, Jenny Tjoelker, Rita Valdez, Christine Vogeley, Cathryn TI Finding the Clinical Nurse Specialist Voice and Articulating Value SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Atherton, Sherri; Busch, Ann; Church, Victoria; Cole, June Ann; Halmquist, Jennifer; Locke, Christy; Patten, Stephen; Richardson, Jenny; Tjoelker, Rita; Valdez, Christine; Vogeley, Cathryn] Portland VA Med Ctr, Portland, OR 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2010 VL 24 IS 2 BP 96 EP 96 PG 1 WC Nursing SC Nursing GA 570QP UT WOS:000275693300038 ER PT J AU Patten, S AF Patten, Stephen TI Partnerships Between Hospitals and Schools of Nursing SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Patten, Stephen] Portland VA Med Ctr, Portland, OR 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2010 VL 24 IS 2 BP 99 EP 99 PG 1 WC Nursing SC Nursing GA 570QP UT WOS:000275693300048 ER PT J AU Fehringer, EV Mikuls, TR Michaud, KD Henderson, WG O'Dell, JR AF Fehringer, Edward V. Mikuls, Ted R. Michaud, Kaleb D. Henderson, William G. O'Dell, James R. TI Shoulder Arthroplasties have Fewer Complications than Hip or Knee Arthroplasties in US Veterans SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SURGICAL CARE; RISK ADJUSTMENT; OUTCOMES; OSTEOARTHRITIS; QUALITY AB Total shoulder arthroplasties (TSA) are being performed more commonly for treatment of arthritis, although fewer than either hip (THA) or knee (TKA) arthroplasties. Total shoulder arthroplasty also provides general health improvements that are comparable to THA. One study suggests TSAs are associated with lower morbidity and mortality than THAs and TKAs. To confirm and extend that study, we therefore examined the association of patient characteristics (sociodemographics, comorbid illness, and other risk factors) with 30-day complications for patients undergoing TSAs, THAs, or TKAs. We used data from the Veterans Administration (VA) National Surgical Quality Improvement Program (NSQIP) for fiscal years 1999 to 2006. Sociodemographics, comorbidities, health behaviors, operative factors, and complications (mortality, return to the operating room, readmission within 14 days, cardiovascular events, and infections) were available for 10,407 THAs, 23,042 TKAs, and 793 TSAs. Sociodemographic features were comparable among groups. The mean operative time was greater for TSAs (3.0 hours) than for TKAs (2.2 hours) and THAs (2.4 hours). The 30-day mortality rates were 1.2%, 1.1%, and 0.4% for THAs, TKAs, and TSAs, respectively. The corresponding postoperative complication rates were 7.6%, 6.8%, and 2.8%. Adjusting for multiple risk factors, complications, readmissions, and postoperative stays were less for TSAs versus THAs and TKAs. In a VA population, TSAs required more operative time but resulted in shorter stays, fewer complications, and fewer readmissions than THAs and TKAs. Level of Evidence: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. C1 [Fehringer, Edward V.] Univ Nebraska Med Ctr, Dept Orthopaed Surg & Rehabil, Omaha, NE 68198 USA. [Fehringer, Edward V.; Mikuls, Ted R.; Michaud, Kaleb D.; O'Dell, James R.] NAORC, Omaha, NE USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, UCD, AMC, Denver, CO 80202 USA. [Henderson, William G.] Denver VA Med Ctr, Denver, CO USA. RP Fehringer, EV (reprint author), Univ Nebraska Med Ctr, Dept Orthopaed Surg & Rehabil, 981080 Nebraska Med Ctr, Omaha, NE 68198 USA. EM evfehringer@unmc.edu NR 16 TC 26 Z9 26 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAR PY 2010 VL 468 IS 3 BP 717 EP 722 DI 10.1007/s11999-009-0996-2 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 558HM UT WOS:000274731700011 PM 19626383 ER PT J AU Lin, HW Shargorodsky, J Gopen, Q AF Lin, Harrison W. Shargorodsky, Josef Gopen, Quinton TI Clinical Strategies for the Management of Acute Mastoiditis in the Pediatric Population SO CLINICAL PEDIATRICS LA English DT Article DE acute mastoiditis; pediatric; otitis media; abscess ID ACUTE OTITIS-MEDIA; CHILDREN; COMPLICATIONS AB Although the incidence of acute mastoiditis has been substantially reduced since the introduction of antibiotic therapy, mastoiditis complications are still commonly seen in the pediatric population. Many of these cases require lengthy hospitalizations and extensive medical and surgical interventions. Accordingly, a safe, effective, and resourceful diagnostic and therapeutic plan must be executed for the workup and treatment of each patient suspected of having acute mastoiditis. With thorough clinical evaluations, early diagnosis, and close follow-up, a large proportion of children with severe acute otitis media or early stage mastoiditis can be managed in the primary care setting without immediate surgical specialty involvement. This review presents an overview of the anatomical and pathophysiological considerations in acute mastoiditis and offers pediatricians a practical, evidence-based algorithm for the diagnostic and therapeutic approach to this disease. C1 [Lin, Harrison W.; Shargorodsky, Josef; Gopen, Quinton] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Gopen, Quinton] Childrens Hosp, Boston, MA 02115 USA. RP Lin, HW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM harrison_lin@meei.harvard.edu NR 17 TC 10 Z9 11 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD MAR PY 2010 VL 49 IS 2 BP 110 EP 115 DI 10.1177/0009922809344349 PG 6 WC Pediatrics SC Pediatrics GA 544SD UT WOS:000273678700002 PM 19734439 ER PT J AU Wang, ML Macklin, EA Tracy, E Nadel, H Catlin, EA AF Wang, Marvin L. Macklin, Eric A. Tracy, Erin Nadel, Hiyam Catlin, Elizabeth A. TI Updated Parental Viewpoints on Male Neonatal Circumcision in the United States SO CLINICAL PEDIATRICS LA English DT Article DE circumcision; HIV; newborn; questionnaire ID URINARY-TRACT-INFECTION; HIV PREVENTION; NEWBORN CIRCUMCISION; RISK; TRIAL; AFRICA; CANCER; MEN AB Through a questionnaire, the authors sought to elicit information about initial attitudes concerning circumcision after reading a summary of the American Academy of Pediatrics (AAP) Policy Statement and, again, after reading a description of recent HIV/HPV studies. Predictors of increased support for circumcision included having a prior circumcised boy and being US born. Predictors of decreased support included being of Hispanic ethnicity and believing that the uncircumcised penis was more culturally normal. After reading the AAP statement, 86% of respondents remained favorable of elective circumcision, whereas 13% viewed it less favorably. After reading the passage about the HIV/HPV studies, the majority maintained their initial level of support. Certain characteristics were associated with an individual's desire to perform circumcision on his/her infant. Despite a slight decrease in support to perform circumcision after reading the AAP policy summary, respondents' initial attitudes toward circumcision were unchanged after subsequent review of recent HIV/HPV research. C1 [Wang, Marvin L.; Tracy, Erin; Nadel, Hiyam; Catlin, Elizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Wang, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Founders 526, Boston, MA 02114 USA. EM mwang1@partners.org RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 NR 26 TC 11 Z9 11 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD MAR PY 2010 VL 49 IS 2 BP 130 EP 136 DI 10.1177/0009922809346569 PG 7 WC Pediatrics SC Pediatrics GA 544SD UT WOS:000273678700005 PM 20080519 ER PT J AU Chang, MH Fung, HB AF Chang, Mei H. Fung, Horatio B. TI Besifloxacin: A Topical Fluoroquinolone for the Treatment of Bacterial Conjunctivitis SO CLINICAL THERAPEUTICS LA English DT Review DE besifloxacin; bacterial conjunctivitis; ophthalmic fluoroquinolones ID OPHTHALMIC SUSPENSION 0.6-PERCENT; ANTIMICROBIAL AGENT; ESCHERICHIA-COLI; SAFETY; PHARMACOKINETICS; INFECTIONS; RESISTANCE; EFFICACY AB Background: Besifloxacin is a topical ophthalmic fluoroquinolone that was approved by the US Food and Drug Administration (FDA) in May 2009 for the treatment of bacterial conjunctivitis caused by susceptible bacterial strains. Objective: This article provides an overview of the pharmacology, clinical efficacy, and tolerability of ophthalmic besifloxacin when used for the treatment of bacterial conjunctivitis. Methods: Relevant reports pertaining to the pharmacology, efficacy, and tolerability of besifloxacin were identified through a search of MEDLINE (1985 December 2009) and International Pharmaceutical Abstracts (1985 December 2009) using the terms besifloxacin, BOL-303224-A, ophthalmic fluoroquinolones, and bacterial conjunctivitis. Additional publications were identified by reviewing the reference lists of identified articles and searching the FDA Web site. Results: Besifloxacin has potent in vitro inhibitory activity against most common ocular bacterial pathogens (MIC(90) values generally <= 4 mu g/mL), including Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. In an ocular pharmacokinetic study in 64 healthy volunteers, the C(max) in tears (mean [SD], 610 [540] mu g/mL) was reached 10 minutes after a single ocular instillation of besifloxacin; concentrations >= 1.6 mu g/g of tear were sustained for at least 24 hours; and the elimination tin. was similar to 3.4 hours. In a study in 24 patients with a clinical diagnosis of bilateral bacterial conjunctivitis, systemic exposure (C(max)) after administration of besifloxacin ophthalmic suspension 3 times daily for 5 days was <0.5 ng/mL. In 2 randomized, double-masked, vehicle-controlled clinical trials, besifloxacin ophthalmic suspension was well tolerated and significantly more efficacious than vehicle in achieving clinical resolution (73.3% vs 43.1%, respectively, in one of the studies [P < 0.001]; 45.2% vs 33.0% in the other [P = 0.008]) and microbial eradication (88.3% vs 60.3% [P < 0.001] and 91.5% vs 59.7% [P < 0.001], respectively). In a randomized, double-masked, parallel-group, noninferiority trial comparing besifloxacin ophthalmic suspension 0.6% with moxifloxacin ophthalmic solution 0.5%, besifloxacin was found to be noninferior to moxifloxacin (predefined cutoff for noninferiority = 15), with no significant differences in rates of clinical resolution (58.3% and 59.4%, respectively; 95% CI, -9.48 to 7.29) or microbial eradication (93.3% and 91.1%; 95% CI, -2.44 to 6.74). Besifloxacin was generally well tolerated in these clinical trials, with the most common >= 1.5%) ocular adverse events being nonspecific conjunctivitis (2.6%), blurred vision (2.1%), bacterial conjunctivitis (1.8%), and eye pain (1.5%). The recommended dose of besifloxacin is 1 drop in the affected eye(s) 3 times daily (4-12 hours apart) for 7 days. Conclusion: Besifloxacin ophthalmic suspension 0.6% appeared to be well tolerated in the populations studied and was efficacious in the treatment of bacterial conjunctivitis caused by susceptible isolates. (Clin Then 2010;32:454-471) (C) 2010 Excerpta Medica Inc. C1 [Chang, Mei H.; Fung, Horatio B.] James J Peters Vet Affairs Med Ctr, Serv Pharm, Bronx, NY 10468 USA. RP Fung, HB (reprint author), James J Peters Vet Affairs Med Ctr, Serv Pharm, 130 W Kings Bridge Rd 119, Bronx, NY 10468 USA. EM horatio.fung@va.gov NR 32 TC 7 Z9 8 U1 0 U2 2 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD MAR PY 2010 VL 32 IS 3 BP 454 EP 471 DI 10.1016/j.clinthera.2010.03.013 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 582XB UT WOS:000276632600004 PM 20399984 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI Antidepressants: Can't Live With Them, Can't Live Without Them SO CNS SPECTRUMS LA English DT Editorial Material ID COMORBIDITY SURVEY REPLICATION; ACUTE MYOCARDIAL-INFARCTION; DEPRESSION; TRIALS; DISORDERS; SEVERITY; EFFICACY C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 13 TC 1 Z9 1 U1 1 U2 1 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAR PY 2010 VL 15 IS 3 BP 146 EP 147 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 574JK UT WOS:000275985000001 PM 20414162 ER PT J AU Keuthen, NJ Koran, LM Aboujaoude, E Large, MD Serpe, RT AF Keuthen, Nancy J. Koran, Lorrin M. Aboujaoude, Elias Large, Michael D. Serpe, Richard T. TI The prevalence of pathologic skin picking in US adults SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE-DISORDER; BODY DYSMORPHIC DISORDER; PSYCHOGENIC EXCORIATION; CLINICAL CHARACTERISTICS; FUNCTIONAL IMPAIRMENT; TRICHOTILLOMANIA; COMORBIDITY; PHENOMENOLOGY AB Objective: Despite increasing recognition of the potentially severe medical and psychosocial costs of pathologic skin picking (PSP), no large-sample, randomized investigation of its prevalence in a national population has been conducted. Method: Two thousand five hundred and thirteen US adults were interviewed during the spring and summer of 2004 in a random-sample, national household computer-assisted phone survey of PSP phenomenology and associated functional impairment. Respondents were classified for subsequent analysis according to proposed diagnostic criteria. Results: Of all respondents, 16.6% endorsed lifetime PSP with noticeable skin damage; 60.3% of these denied picking secondary to an inflammation or itch from a medical condition. One fifth to one quarter of those with lifetime PSP not related to a medical condition endorsed tension or nervousness before picking, tension or nervousness when attempting to resist picking, and pleasure or relief during or after picking. A total of 1.4% of our entire sample satisfied our criteria of picking with noticeable skin damage not attributable to another condition and with associated distress or psychosocial impairment. Pickers satisfying these latter criteria differed from other respondents in demographics (age, marital status) and both picking phenomenology and frequency. (C) 2010 Elsevier Inc. All rights reserved. C1 [Keuthen, Nancy J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Keuthen, Nancy J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Koran, Lorrin M.; Aboujaoude, Elias] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Large, Michael D.] Palomar Coll, Dept Inst Res & Planning, San Marino, CA 92069 USA. [Serpe, Richard T.] Kent State Univ, Dept Sociol, Kent, OH 44242 USA. RP Keuthen, NJ (reprint author), Clin Massachusetts Gen Hosp, Boston, MA 02114 USA. EM nkeuthen@partners.org RI Citations, TLC SAB/C-4006-2011 FU Forest Pharmaceuticals; Eli Lilly; Somaxon; Pfizer FX This research was funded by Forest Pharmaceuticals (grant awarded to Dr. Serpe). Drs. Koran and Aboujaoude are on the speaker's bureau for Forest Pharmaceuticals. Dr. Aboujaoude is also on the speaker's bureau for Jazz Pharmaceuticals. Drs. Koran and Aboujaoude had research grants from Eli Lilly and Somaxon at the time the study was conducted. Dr. Keuthen has received research/grant support from Eli Lilly, Pfizer, and Forest Pharmaceuticals. Drs. Koran, Aboujaoude, and Keuthen did not receive any financial support from this grant. Drs. Serpe and Large have no financial disclosures or conflicts of interest to report. Our research was approved by a Human Research Committee prior to enrollment of subjects in the study. NR 27 TC 48 Z9 48 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAR-APR PY 2010 VL 51 IS 2 BP 183 EP 186 DI 10.1016/j.comppsych.2009.04.003 PG 4 WC Psychiatry SC Psychiatry GA 702VC UT WOS:000285923000014 PM 20152300 ER PT J AU Bechard, LJ Feldman, HA Gordon, C Gura, K Sonis, A Leung, K Venick, R Guinan, EC Duggan, C AF Bechard, Lori J. Feldman, Henry A. Gordon, Catherine Gura, Kathleen Sonis, Andrew Leung, Kathryn Venick, Robert Guinan, Eva C. Duggan, Christopher TI A multi-center, randomized, controlled trial of parenteral nutrition titrated to resting energy expenditure in children undergoing hematopoietic stem cell transplantation ("PNTREE"): Rationale and design SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Hematopoietic stem cell transplantation; Parenteral nutrition; Body composition; Energy expenditure ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; BODY-COMPOSITION; CHILDHOOD; YOUNG; HYPERGLYCEMIA; POPULATION; MASS; VENTILATION; RESUMPTION AB Background: Children undergoing hematopoietic stem cell transplantation (HSCT) frequently require prolonged courses of parenteral nutrition (PN) as a consequence of gastrointestinal dysfunction related to preparative chemotherapy and radiation. PN has been associated with shorter engraftment time and decreased mortality during HSCT, however, it is also linked with complications, including infections, liver disease, and metabolic disturbances. Some of these complications may be a result of providing PN in excess of nutrient requirements. We previously described significant reductions in resting energy expenditure (REE), as measured by indirect calorimetry, over the course of HSCT. We also documented a decline in mid-arm muscle area, suggesting depletion of muscle mass, while triceps skinfold, a marker of fat stores, was unchanged. These results suggested the need for further study of energy expenditure, body composition and nutritional intake in this group of high risk patients. Design and hypothesis: We hypothesize that changes in body composition affect REE during HSCT, and that standard nutritional support may lead to overfeeding. We are performing a randomized controlled trial of parenteral nutrition among children undergoing allogeneic HSCT. Subjects are randomized to receive PN designed to provide 100% of measured REE, or standard PN, i.e., 140% of estimated energy expenditure. The primary outcome variable is change in percent body fat. Secondary outcomes include glycemic control and frequency of infections, changes in REE and body composition. Conclusion: This study will provide unique and comprehensive nutritional data and its results will guide nutritional therapy for children undergoing HSCT and possibly other catabolic patients. (C) 2009 Elsevier Inc. All rights reserved. C1 [Duggan, Christopher] Childrens Hosp, Div GI Nutr, Boston, MA 02115 USA. [Bechard, Lori J.; Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Leung, Kathryn] Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Venick, Robert] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA 90095 USA. RP Duggan, C (reprint author), Childrens Hosp, Div GI Nutr, 300 Longwood Ave, Boston, MA 02115 USA. EM christopher.duggan@childrens.harvard.edu FU Massachusetts Vitamin Litigation; NCRR, NIH [M01-RR02172]; [UL1 RR025758-01]; [M01-RR00865]; [M01-RR00188] FX We appreciate the valuable contributions of our subjects, and the helpful assistance of Janet Mooney, RN, Elena Khanukova, Nicolle Quinn, M.S., RD., and Melissa O'Connor, RN, PNP. This project is supported by the Massachusetts Vitamin Litigation Grant; grant M01-RR02172 from the NCRR, NIH to Children's Hospital, Boston GCRC; grant UL1 RR025758-01 to the Harvard Catalyst CTSA 1; grant M01-RR00865 to the General Clinical Research Centers Program at UCLA; and grant M01-RR00188 to the General Clinical Research Center at Baylor College of Medicine. NR 48 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAR PY 2010 VL 31 IS 2 BP 157 EP 164 DI 10.1016/j.cct.2009.12.002 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 576FJ UT WOS:000276129400006 PM 20004739 ER PT J AU Azar, DT Casanova, FH Mimura, T Jain, S Zhou, ZJ Han, KY Chang, JH AF Azar, Dimitri T. Casanova, Fabio H. Mimura, Tatsuya Jain, Sandeep Zhou, Zhongjun Han, Kyu Yeon Chang, Jin-Hong TI Corneal Epithelial MT1-MMP Inhibits Vascular Endothelial Cell Proliferation and Migration SO CORNEA LA English DT Article DE cornea; MT1-MMP; TIMP; epithelium ID TYPE-1 MATRIX-METALLOPROTEINASE; IN-VITRO; TISSUE INHIBITOR; ANGIOGENESIS; SURFACE; VEGF; NEOVASCULARIZATION; OLIGOMERIZATION; AVASCULARITY; PROTEOLYSIS AB Purpose: To determine the effects of corneal epithelial membrane-type 1 matrix metalloproteinase (MT1-MMP) on vascular endothelial migration and proliferation. Methods: We generated immortalized wild-type, MT1-MMP knockout and MT1-MMP knock-in corneal epithelial cells. Calf pulmonary arterial endothelial (CPAE) cell proliferation and Boyden chamber migration were assayed. Results: Conditioned media from MT1-MMP epithelial knockout cells significantly increased CPAE proliferation 5-bromo-2'-deoxyuridine (BrdU) incorporation, and CPAE migration as compared with wild-type epithelial cells. Conditioned media from knock-in cells reversed the increase in CPAE proliferation, BrdU incorporation and CPAE migration. Knock-in cells transfected with mutant MT1-MMP (E240A) did not abrogate the reversal effect. Conclusions: Corneal epithelial MT1-MMP is antiangiogenic. This antiangiogenic activity does not require the catalytic domain. C1 [Azar, Dimitri T.; Mimura, Tatsuya; Jain, Sandeep; Han, Kyu Yeon; Chang, Jin-Hong] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. [Azar, Dimitri T.; Casanova, Fabio H.; Mimura, Tatsuya; Chang, Jin-Hong] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Azar, Dimitri T.; Casanova, Fabio H.; Jain, Sandeep; Chang, Jin-Hong] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Zhou, Zhongjun] Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. RP Azar, DT (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM dazar@uic.edu RI zhou, zhongjun/D-4818-2012 FU National Institutes of Health [EY10101, EY001792, EY14048]; Research to Prevent Blindness FX Supported by National Institutes of Health grants EY10101 ( D. T. A.), EY001792 ( D. T. A.), and EY14048 (J.H.C.) and an unrestricted departmental grant from Research to Prevent Blindness. NR 34 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD MAR PY 2010 VL 29 IS 3 BP 321 EP 330 DI 10.1097/ICO.0b013e3181b1165d PG 10 WC Ophthalmology SC Ophthalmology GA 561WX UT WOS:000275011900015 PM 20118785 ER PT J AU Nelson, JE Puntillo, KA Pronovost, PJ Walker, AS McAdam, JL Ilaoa, D Penrod, J AF Nelson, Judith E. Puntillo, Kathleen A. Pronovost, Peter J. Walker, Amy S. McAdam, Jennifer L. Ilaoa, Debra Penrod, Joan TI In their own words: Patients and families define high-quality palliative care in the intensive care unit SO CRITICAL CARE MEDICINE LA English DT Article DE intensive care; critical care; palliative care; quality assessment; health care; quality indicators; qualitative research ID OF-LIFE CARE; CRITICALLY-ILL; CONTROLLED-TRIAL; VISITING POLICY; MEDICAL-CARE; HEALTH-CARE; END; ICU; PAIN; MEMBERS AB Objective: Although the majority of hospital deaths occur in the intensive care unit and virtually all critically ill patients and their families have palliative needs, we know little about how patients and families, the most important "stakeholders," define high-quality intensive care unit palliative care. We conducted this study to obtain their views on important domains of this care. Design: Qualitative study using focus groups facilitated by a single physician. Setting: A 20-bed general intensive care unit in a 382-bed community hospital in Oklahoma; 24-bed medical-surgical intensive care unit in a 377-bed tertiary, university hospital in urban California; and eight-bed medical intensive care unit in a 311-bed Veterans' Affairs hospital in a northeastern city. Patients: Randomly-selected patients with intensive care unit length of stay >= 5 days in 2007 to 2008 who survived the intensive care unit, families of survivors, and families of patients who died in the intensive care unit. Interventions: None. Measurements and Main Results: Focus group facilitator used open-ended questions and scripted probes from a written guide. Three investigators independently coded meeting transcripts, achieving consensus on themes. From 48 subjects (15 patients, 33 family members) in nine focus groups across three sites, a shared definition of high-quality intensive care unit palliative care emerged: timely, clear, and compassionate communication by clinicians; clinical decision-making focused on patients' preferences, goals, and values; patient care maintaining comfort, dignity, and personhood; and family care with open access and proximity to patients, interdisciplinary support in the intensive care unit, and bereavement care for families of patients who died. Participants also endorsed specific processes to operationalize the care they considered important. Conclusions: Efforts to improve intensive care unit palliative care quality should focus on domains and processes that are most valued by critically ill patients and their families, among whom we found broad agreement in a diverse sample. Measures of quality and effective interventions exist to improve care in domains that are important to intensive care unit patients and families. (Crit Care Med 2010; 38: 808-818) C1 [Nelson, Judith E.; Walker, Amy S.] Mt Sinai Sch Med, Div Pulm Crit Care & Sleep Med, New York, NY 10029 USA. [Nelson, Judith E.] Mt Sinai Sch Med, Hertzberg Palliat Care Inst, New York, NY USA. [Puntillo, Kathleen A.; McAdam, Jennifer L.] Univ Calif San Francisco, Dept Physiol Nursing, Crit Care Trauma Program, San Francisco, CA 94143 USA. [Pronovost, Peter J.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol Crit Care Med Nursing & Surg, Baltimore, MD USA. [Pronovost, Peter J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [McAdam, Jennifer L.] Dominican Univ Calif, Dept Nursing, San Rafael, CA USA. [Ilaoa, Debra] Norman Reg Hosp, Palliat Care Serv, Norman, OK USA. [Penrod, Joan] James J Peters VA Med Ctr, Ctr Study Hlth Care Syst & Sites Care, Bronx, NY USA. [Penrod, Joan] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. RP Nelson, JE (reprint author), Mt Sinai Sch Med, Div Pulm Crit Care & Sleep Med, New York, NY 10029 USA. EM judith.nelson@mssm.edu FU National Institute on Aging (NIA) [R21-AG029955, K02-AG024476]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [REA 08-260] FX This work was supported by R21-AG029955 from the National Institute on Aging (NIA). Dr. Nelson received an Independent Scientist Award from NIA, K02-AG024476. Dr. Penrod was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (project no. REA 08-260). Dr. Nelson and Dr. Pronovost served as consultants to the Voluntary Hospital Association, Inc., a national cooperative of not-for-profit, community-based hospitals, for development of ICU palliative care quality indicators. NR 50 TC 88 Z9 91 U1 4 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2010 VL 38 IS 3 BP 808 EP 818 DI 10.1097/CCM.0b013e3181c5887c PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 565CI UT WOS:000275266200010 PM 20198726 ER PT J AU Frick, CG Helming, M Martyn, JAJ Blobner, M Fink, H AF Frick, Christiane G. Helming, Marc Martyn, J. A. Jeevendra Blobner, Manfred Fink, Heidrun TI Continuous administration of pyridostigmine improves immobilization-induced neuromuscular weakness SO CRITICAL CARE MEDICINE LA English DT Article DE acetylcholine receptors; critical illness; immobilization; muscle function; muscle relaxant; pyridostigmine ID ACETYLCHOLINE-RECEPTORS; CRITICAL ILLNESS; MYASTHENIA-GRAVIS; JUNCTION; NEOSTIGMINE; MECHANISMS; EXPRESSION; RESISTANCE; DIAPHRAGM; ATROPHY AB Objective: To investigate the effects of continuous pyridostigmine infusion on immobilization-induced muscle weakness. Critical illness often results in immobilization of limb and respiratory muscles, leading to muscle atrophy and up-regulation of nicotinic acetylcholine receptors. Pyridostigmine reversibly blocks acetylcholinesterase and has the potential to improve neuromuscular transmission and decrease acetylcholine receptor number. Design: Prospective, randomized,controlled experimental study. Setting: Animal laboratory, university hospital. Subjects: Male Sprague-Dawley rats. Interventions: A total of 40 rats were immobilized in one hind limb by pinning knee and ankle joints. Rats received either continuous pyridostigmine (15 mg.kg(-1).day(-1)) or saline subcutaneously via implanted osmotic pumps. Measurements and Main Results: After 7 days and 14 days of immobilization, neuromuscular function, atracurium pharmacodynamics, and expression of acetylcholine receptors were evaluated. At 7 days and 14 days after immobilization, muscle force decreased in all untreated groups, whereas effective doses for paralysis with atracurium and acetylcholine receptor number in the tibialis were significantly increased. Pyridostigmine-treated rats showed a significantly improved muscle force and muscle mass in the immobilized limb. This was associated with an attenuation of acetylcholine receptor up-regulation in the respective leg. At this time, the dose-response curve for atracurium on the immobilized side was shifted to the left in the pyridostigmine group. After 14 days, muscle tension was still less depressed with pyridostigmine infusion, and resistance to the effects of atracurium was still attenuated. However, there were no differences in acetylcholine receptor expression between the immobilized sides of both groups. Conclusions: Continuous pyridostigmine infusion improves muscle weakness after 7 days and 14 days of immobilization. The up-regulation of acetylcholine receptors and the concomitant resistance to atracurium is attenuated in animals treated with pyridostigmine after 7 days of immobilization. (Crit Care Med 2010; 38:922-927) C1 [Frick, Christiane G.; Helming, Marc; Blobner, Manfred; Fink, Heidrun] Tech Univ Munich, Klinikum Rechts Isar, Klin Anaesthesiol, D-8000 Munich, Germany. [Frick, Christiane G.; Martyn, J. A. Jeevendra] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. Shriners Hosp Children, Boston, MA USA. RP Frick, CG (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Klin Anaesthesiol, D-8000 Munich, Germany. EM c.frick@lrz.tu-muenchen.de OI Lewald, Heidrun/0000-0002-5192-425X FU Klinikum rechts der Isar; National Institutes of Health [GM 31569-25, GM 2150-36, GM 055082-11]; Shriners Hospital Research Philantrophy, Tampa, FL FX This study was supported, in part, by institutional funds of Klinikum rechts der Isar and by Grants GM 31569-25, GM 2150-36-ProjectIV, and GM 055082-11 from the National Institutes of Health and Shriners Hospital Research Philantrophy, Tampa, FL (J.A.J.M.). NR 27 TC 3 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2010 VL 38 IS 3 BP 922 EP 927 DI 10.1097/CCM.0b013e3181c31297 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 565CI UT WOS:000275266200026 PM 20009758 ER PT J AU Marill, KA Wolfram, S deSouza, IS Nishijima, DK Kay, D Setnik, GS Stair, TO Ellinor, PT AF Marill, Keith A. Wolfram, Sigrid deSouza, Ian S. Nishijima, Daniel K. Kay, Darren Setnik, Gary S. Stair, Thomas O. Ellinor, Patrick T. TI The use of adenosine in patients with wide complex supraventricular tachycardias Reply SO CRITICAL CARE MEDICINE LA English DT Letter C1 [Marill, Keith A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Wolfram, Sigrid; deSouza, Ian S.] Suny Downstate Med Ctr, Dept Emergency Med, Brooklyn, NY 11203 USA. [Nishijima, Daniel K.] Univ Calif Davis, Med Ctr, Dept Emergency Med, Sacramento, CA 95817 USA. [Kay, Darren] NW Med Ctr, Emergency Dept, Tucson, AZ USA. [Setnik, Gary S.] Mt Auburn Hosp, Dept Emergency Med, Cambridge, MA USA. [Stair, Thomas O.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Marill, KA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2010 VL 38 IS 3 BP 1017 EP 1017 DI 10.1097/CCM.0b013e3181cfb760 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 565CI UT WOS:000275266200067 ER PT J AU Berra, L Cressoni, M Bassi, GL Kolobow, T Panigada, M Zanella, A AF Berra, Lorenzo Cressoni, Massimo Li Bassi, Gianluigi Kolobow, Theodor Panigada, Mauro Zanella, Alberto CA Gravity VAP Network TI Continuous lateral rotation therapy to prevent ventilator-associated pneumonia: The neglected effects of gravity on pathogenesis of ventilator-associated pneumonia SO CRITICAL CARE MEDICINE LA English DT Letter C1 [Berra, Lorenzo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cressoni, Massimo; Panigada, Mauro] Fdn IRCCS Policlin, Milan, Italy. [Li Bassi, Gianluigi] Hosp Clin Barcelona, Barcelona, Spain. [Kolobow, Theodor] NIH, Bethesda, MD 20892 USA. [Zanella, Alberto] Osped San Gerardo, Monza, Italy. RP Berra, L (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Cressoni, Massimo/B-7315-2017; Panigada, Mauro/K-4650-2014; OI Cressoni, Massimo/0000-0002-0089-2905; Panigada, Mauro/0000-0003-4841-9794; zanella, Alberto/0000-0002-2967-2527 NR 3 TC 0 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2010 VL 38 IS 3 BP 1018 EP 1019 DI 10.1097/CCM.0b013e3181cc40fc PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 565CI UT WOS:000275266200070 PM 20168183 ER PT J AU Roy, M Mahmood, N Rosendorff, C AF Roy, Monisankar Mahmood, Noman Rosendorff, Clive TI Evidence for Aggressive Blood Pressure-Lowering Goals in Patients with Coronary Artery Disease SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE BP goals; Coronary artery disease; Hypertension; Blood pressure; J curve ID ISOLATED SYSTOLIC HYPERTENSION; LEFT-VENTRICULAR HYPERTROPHY; CARDIOVASCULAR-DISEASE; RANDOMIZED-TRIAL; HEART-DISEASE; ACTIVE TREATMENT; MORTALITY; RISK; FLOW; ATHEROSCLEROSIS AB Lowering blood pressure (BP) reduces the risk of major cardiovascular mortality and morbidity. Current consensus targets for BP reduction are less than 140/90 mm Hg in uncomplicated hypertension and less than 130/80 mm Hg in those patients with diabetes, chronic kidney disease, and coronary artery disease or in those who are at high risk for developing coronary artery disease (defined as a Framingham risk score of a parts per thousand yen 10%). There is solid epidemiologic evidence for lower BP targets, supported by some clinical studies with surrogate end points. On the other hand, there are meager data from clinical trials using hard end points, and there is a concern that overly aggressive BP lowering, especially of diastolic BP, may impair coronary perfusion, particularly in patients with left ventricular hypertrophy and/or coronary artery disease. This review evaluates the evidence for the benefit of lower BP targets in hypertension management. C1 [Roy, Monisankar; Mahmood, Noman; Rosendorff, Clive] Mt Sinai Sch Med, James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Rosendorff, C (reprint author), Mt Sinai Sch Med, James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM monisankar.roy@va.gov; noman.mahmood@va.gov; clive.rosendorff@va.gov NR 40 TC 5 Z9 5 U1 0 U2 0 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 J9 CURR ATHEROSCLER REP JI Curr. Atherosclerol. Rep. PD MAR PY 2010 VL 12 IS 2 BP 134 EP 139 DI 10.1007/s11883-010-0094-7 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 583DW UT WOS:000276654300008 PM 20425249 ER PT J AU Yu, LY Garg, HG Li, B Linhardt, RJ Hales, CA AF Yu, Lunyin Garg, Hari G. Li, Boyangzi Linhardt, Robert J. Hales, Charles A. TI Antitumor Effect of Butanoylated Heparin with Low Anticoagulant Activity on Lung Cancer Growth in Mice and Rats SO CURRENT CANCER DRUG TARGETS LA English DT Review DE Heparin; butanoylated; antitumor; lung cancer; mice; rats ID MOLECULAR-WEIGHT HEPARIN; SMOOTH-MUSCLE-CELLS; CHEMICALLY-MODIFIED HEPARIN; CHEMOKINE RECEPTOR CXCR4; INDUCED PULMONARY-HYPERTENSION; IN-VITRO; CARCINOMA CELLS; P-SELECTIN; ANTIPROLIFERATIVE ACTIVITY; TUMOR-GROWTH AB Whole unfractionated heparin can modestly decrease tumor growth, but the dose of heparin is limited by its anticoagulant properties. To overcome this limitation, we modified the chemical structure of heparin and have prepared a heparin derivative by O-acylating low molecular weight heparin with butyric anhydride, producing a more potent antiproliferative compound, which is only weakly anticoagulant so that the dose may be escalated without threat of hemorrhage. In this study, we investigated the effect of this chemically modified heparin, butanoylated heparin, on the growth of lung cancer in vitro and in vivo. We found that butanoylated heparin a) significantly inhibited lung cancer cell proliferation in vitro and lung cancer growth in mice and rats; b) had very low anticoagulant effect; c) had no significant toxicity on heart, liver, kidney and lung; d) significantly although modestly induced apoptosis and decreased expression of the cell proliferation pathway consisting of mutant p53, phospho-Rb and E2F1 expression in the tumor tissues. We also found that butanoylated heparin significantly inhibited CXCL12 and CXCR4 expression, suggesting that CXCL12/CXCR4 axis may be involved in regulation of tumor growth inhibition by heparin. We concluded that chemically modified butanoylated heparin has potent antiproliferative activity against lung cancer and may represent a new chemical therapeutic agent for cancer patients. C1 [Yu, Lunyin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA. [Li, Boyangzi; Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Chem & Chem Biol, Biotechnol Ctr 4005, Troy, NY 12180 USA. [Li, Boyangzi; Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Biol, Biotechnol Ctr 4005, Troy, NY 12180 USA. [Li, Boyangzi; Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Chem & Biol Engn, Biotechnol Ctr 4005, Troy, NY 12180 USA. RP Yu, LY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM lyu3@partners.org RI Li, Boyangzi/B-4813-2012 FU NIH [HL39150]; ATS/Pulmonary Hypertension Association [PH-08-010]; Susan Wood Fund FX This work was supported by NIH grants HL39150 (C.A. Hales), ATS/Pulmonary Hypertension Association Partnership Research Grant PH-08-010 (L. Yu) and a grant from the Susan Wood Fund. NR 71 TC 9 Z9 13 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD MAR PY 2010 VL 10 IS 2 BP 229 EP 241 PG 13 WC Oncology SC Oncology GA 579YB UT WOS:000276412300010 PM 20201787 ER PT J AU Bianchi, MT AF Bianchi, Matt T. TI Context Dependent Benzodiazepine Modulation of GABA(A) Receptor Opening Frequency SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Mechanism; ion channel; synaptic; extra-synaptic; affinity ID DIAZEPAM-INDUCED CHANGES; MOUSE SPINAL NEURONS; A RECEPTORS; DESENSITIZED STATES; KINETIC-PROPERTIES; GAMMA; CURRENTS; CHANNELS; SUBTYPES; AGONISTS AB The anxiolytic, hypnotic, and anti-convulsant properties of benzodiazepines (BDZs) require modulation of distinct GABA(A) receptor alpha-subtypes. BDZ modulation of GABA(A) receptors is often described in terms of increased opening frequency, and contrasted with the increased open durations occurring with barbiturate modulation. Several studies spanning single channel, rapid kinetic, and whole cell techniques have suggested that BDZs effect this observed change in frequency through increased affinity for GABA. BDZ-sensitive alpha beta gamma isoforms exist at extrasynaptic as well as synaptic locations, where they encounter markedly different concentration and time-course of GABA exposure. Interestingly, this affinity-based mechanism (specifically, decreasing the GABA unbinding rate) is only predicted to increase opening frequency under conditions that allow the unbinding and rebinding cycles typical of prolonged exposure to low GABA concentrations, which are more likely to occur at extrasynaptic GABA(A) receptors. In contrast, when rebinding is less likely, such as may occur in certain synaptic conditions, the number, but not the frequency, of channel openings increases in response to BDZ modulation. In conclusion, not only can multiple kinetic mechanisms alter channel opening frequency, but a single mechanism - increased affinity - impacts opening frequency differently under different contexts of GABA(A) receptor activation. C1 Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Sleep Div, 55 Fruit St,WAC-720, Boston, MA 02114 USA. EM mtbianchi@partners.org NR 56 TC 12 Z9 12 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD MAR PY 2010 VL 8 IS 1 BP 10 EP 17 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 568JB UT WOS:000275517500003 PM 20808542 ER PT J AU Cleary, JM Shapiro, GI AF Cleary, James M. Shapiro, Geoffrey I. TI Development of Phosphoinositide-3 Kinase Pathway Inhibitors for Advanced Cancer SO CURRENT ONCOLOGY REPORTS LA English DT Article DE Phosphoinositide-3 kinase; Targeted therapy.; Drug development ID LUNG-CANCER; CELL-PROLIFERATION; P110-DELTA ISOFORM; ANTITUMOR-ACTIVITY; 3-KINASE; PI3K; RESISTANCE; GROWTH; ACTIVATION; NVP-BEZ235 AB The phosphoinositide-3 kinase (PI3K) pathway plays a critical role in cancer cell growth and survival. PI3K is activated in human cancers by elevated receptor tyrosine kinase activity, RAS mutation, as well as by mutation, amplification, and deletion of genes encoding components of the pathway. Additionally, PI3K pathway activation plays an important role in acquired resistance to both chemotherapy and targeted agents. The essential role of PI3K in human cancer has led to the development of PI3K pathway inhibitors that have shown promise in preclinical models and have entered phase 1 clinical trials. This article reviews preclinical and clinical data on members of this novel drug class, as well as data justifying the combination of PI3K inhibitors with other anticancer agents. C1 [Cleary, James M.; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Early Drug Dev Ctr, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Early Drug Dev Ctr, 44 Binney St, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu FU NCI NIH HHS [U01 CA062490-16, U01 CA062490] NR 54 TC 32 Z9 32 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD MAR PY 2010 VL 12 IS 2 BP 87 EP 94 DI 10.1007/s11912-010-0091-6 PG 8 WC Oncology SC Oncology GA 723IF UT WOS:000287499400003 PM 20425592 ER PT J AU Bonda, DJ Lee, HP Lee, HG Friedlich, AL Perry, G Zhu, XW Smith, MA AF Bonda, David J. Lee, Hyun-Pil Lee, Hyoung-gon Friedlich, Avi L. Perry, George Zhu, Xiongwei Smith, Mark A. TI Novel therapeutics for Alzheimer's disease: An update SO CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT LA English DT Review DE A beta modulator; Alzheimer's disease; antioxidant; cholinesterase inhibitor; excitotoxicity; mitochondrial dynamics; neurofibrillary tangle; oxidative stress; tau; therapeutic ID PAIRED HELICAL FILAMENTS; ACETYL-L-CARNITINE; ALPHA-LIPOIC-ACID; ABNORMAL MITOCHONDRIAL DYNAMICS; GAMMA-SECRETASE INHIBITOR; AMYLOID-BETA PEPTIDE; REDOX-ACTIVE IRON; A-BETA; OXIDATIVE STRESS; TRANSGENIC MICE AB As the most prevalent form of dementia worldwide, Alzheimer's disease (AD) continues to be a burden for patients and their families. In addition, with the global population of aged individuals increasing exponentially, AD represents a significant economic burden to society. The development of an effective approach for the treatment of AD is thus of major importance, as current treatment strategies are limited to agents that attenuate disease symptomatology without addressing the causes of disease. A considerable need exists for the development of an effective therapy to prevent, or at least delay, the progression of AD. Current hypotheses for the pathogenesis of AD are discussed in this review, with a particular emphasis on the implications of these hypotheses with respect to treatment strategies and preventive measures. C1 [Bonda, David J.; Lee, Hyun-Pil; Lee, Hyoung-gon; Perry, George; Zhu, Xiongwei; Smith, Mark A.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Friedlich, Avi L.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Friedlich, Avi L.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Perry, George] Univ Texas San Antonio, Inst Neurosci, San Antonio, TX 78249 USA. [Perry, George] Univ Texas San Antonio, Dept Biol, San Antonio, TX 78249 USA. RP Smith, MA (reprint author), Case Western Reserve Univ, Dept Pathol, 2103 Cornell Rd, Cleveland, OH 44106 USA. EM mark.smith@case.edu RI Smith, Mark/A-9053-2009; Lee, Hyoung-gon/A-9637-2009; Zhu, Xiongwei/A-9629-2009; Perry, George/A-8611-2009 OI Perry, George/0000-0002-6547-0172 FU NIH [AG028679, AG031853]; Alzheimer's Association FX Research in the authors' laboratories is supported by the NIH (AG028679 awarded to Mark A Smith; AG031853 awarded to Xiongwei Zhu) and the Alzheimer's Association. NR 165 TC 25 Z9 27 U1 0 U2 9 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1367-6733 J9 CURR OPIN DRUG DISC JI Curr. Opin. Drug Discov. Dev. PD MAR PY 2010 VL 13 IS 2 BP 235 EP 246 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 563NK UT WOS:000275139100009 PM 20205057 ER PT J AU Soni, RK Weisbord, SD Unruh, ML AF Soni, Ritu K. Weisbord, Steven D. Unruh, Mark L. TI Health-related quality of life outcomes in chronic kidney disease SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE anemia; chronic kidney disease; frailty; hypertension; quality of life; symptom burden ID CHRONIC RENAL-INSUFFICIENCY; ANEMIA CORRECTION; DIALYSIS PATIENTS; AFRICAN-AMERICAN; EPOETIN-ALPHA; HYPERTENSIVE PATIENTS; HEMOGLOBIN TARGET; NATIONAL-HEALTH; OLDER-ADULTS; FRAILTY AB Purpose of review Patients with chronic kidney disease (CKD) endure compromised health-related quality of life (HRQOL). Although the link between HRQOL and increased mortality in patients with end-stage renal disease (ESRD) is well documented, less is known about the relationship between CKD and HRQOL. This article reviews the recent evidence on HRQOL, its correlates and proposed intervention strategies to improve HRQOL in CKD. Recent findings A growing body of literature indicates that various comorbid conditions related to CKD play a substantial role in impaired HRQOL in CKD. Hypertension, both a cause and complication of CKD, negatively affects HRQOL due to associated comorbidities, side effects from antihypertensive medications and awareness of the diagnosis. Anemia has been associated with HRQOL, but concerns about the safety of erythropoietin-stimulating agents (ESAs) have led to more conservative anemia treatment. Frailty, symptom burden and depression are also major contributory factors to HRQOL in CKD. Summary Certain determinants of HRQOL in CKD, namely anemia and depression, are treatable. Early identification and correction may improve overall well being of patients. Clinical trials are required to demonstrate whether treatment interventions benefit HRQOL in this high-risk population. Furthermore, whether integration of HRQOL assessment into routine clinical practice will improve HRQOL outcomes remains to be determined. C1 [Weisbord, Steven D.; Unruh, Mark L.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Med Ctr, Pittsburgh, PA 15213 USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Med Specialty Serv Line, Renal Sect, Pittsburgh, PA USA. [Weisbord, Steven D.] Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Unruh, ML (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Med Ctr, 200 Lothrop St,PUH C-1111, Pittsburgh, PA 15213 USA. EM unruh@pitt.edu FU NIDDK NIH HHS [K23 DK066006, DK66006, DK77785, K23 DK066006-05, R01 DK077785, R01 DK077785-04] NR 59 TC 44 Z9 46 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAR PY 2010 VL 19 IS 2 BP 153 EP 159 DI 10.1097/MNH.0b013e328335f939 PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 562OU UT WOS:000275062900005 PM 20051850 ER PT J AU Fleischhacker, WW DeLisi, LE AF Fleischhacker, W. Wolfgang DeLisi, Lynn E. TI Schizophrenia treatment: entering a new decade SO CURRENT OPINION IN PSYCHIATRY LA English DT Editorial Material C1 [Fleischhacker, W. Wolfgang] Med Univ Innsbruck, Biol Psychiat Div, Dept Psychiat & Psychotherapy, Innsbruck, Austria. [DeLisi, Lynn E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [DeLisi, Lynn E.] VA Boston Healthcare Syst, Brockton, MA USA. RP Fleischhacker, WW (reprint author), Med Univ Innsbruck, Biol Psychiat Div, Dept Psychiat & Psychotherapy, Innsbruck, Austria. EM wolfgang.fleischhacker@i-med.ac.at NR 4 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAR PY 2010 VL 23 IS 2 BP 83 EP 84 DI 10.1097/YCO.0b013e32833779eb PG 2 WC Psychiatry SC Psychiatry GA 559DC UT WOS:000274799900001 PM 20124788 ER PT J AU Sakhuja, R Yeh, RW Bhatt, DL AF Sakhuja, Rahul Yeh, Robert W. Bhatt, Deepak L. TI Antiplatelet Agents in Acute Coronary Syndromes SO CURRENT PROBLEMS IN CARDIOLOGY LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; ELUTING STENT IMPLANTATION; GLYCOPROTEIN IIB/IIIA INHIBITION; TISSUE-PLASMINOGEN ACTIVATOR; UNSTABLE ANGINA-PECTORIS; IIB-IIIA INHIBITORS; HIGH-RISK PATIENTS AB The platelet plays an essential role in atherothrombosis. Clinically, platelet-rich thrombi underlie acute coronary syndromes (ACSs). Current therapies have improved outcomes, however, often at the expense of increased risk of bleeding. With the increase in our understanding of the underlying pathophysiology of ACSs, newer targets for antiplatelet therapies continue to emerge. Novel antiplatelet agents may provide even greater reductions in ischemic events with the potential for less bleeding. This article reviews the evidence for current antiplatelet agents in ACSs as well as for the newer agents in later phases of clinical testing. (Curr Probl Cardiol 2010;35:123-170.) C1 [Sakhuja, Rahul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yeh, Robert W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Integrated Intervent Cardiovasc Program, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Sakhuja, R (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI bashzar, salman/R-5748-2016 FU Bristol-Myers Squibb; EISAI; Ethicon, Heartscape; Sanofi Aventis; Medicines Company; Consultant/Advisory Board-Arena; AstraZeneca; Cardax; Centocor; Cogentus; Daiichi-Sankyo; Eli Lilly; GlaxoSmithKline; Johnson and Johnson; Mcneil; Medtronic; Millennium; Otsuka; Paringenix; PDL; Philips; Porto la; Schering Plough; Vertex FX Dr. Bhatt received research grants (to the institution) from the following sponsors: Bristol-Myers Squibb, EISAI, Ethicon, Heartscape, Sanofi Aventis, the Medicines Company; Consultant/Advisory Board-Arena, AstraZeneca, Bristol-Myers Squibb, Cardax, Centocor, Cogentus, Daiichi-Sankyo, EISAI, Eli Lilly, GlaxoSmithKline, Johnson and Johnson, Mcneil, Medtronic, Millennium, Otsuka, Paringenix, PDL, Philips, Porto la, Sanofi Aventis, Schering Plough, the Medicines Company, and Vertex. Dr. Yeh received a research grant from Schering Plough. NR 156 TC 10 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0146-2806 J9 CURR PROB CARDIOLOGY JI Curr. Probl. Cardiol. PD MAR PY 2010 VL 35 IS 3 BP 123 EP 170 DI 10.1016/j.cpcardio1.2009.11.002 PG 48 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 599YU UT WOS:000277951100002 PM 20152547 ER PT J AU Carlozzi, NE Horner, MD Kose, S Yamanaka, K Mishory, A Mu, Q Nahas, Z Wells, SA George, MS AF Carlozzi, Noelle E. Horner, Michael David Kose, Samet Yamanaka, Kaori Mishory, Alexander Mu, Qiwen Nahas, Ziad Wells, Sarah A. George, Mark S. TI Personality and Reaction Time after Sleep Deprivation SO CURRENT PSYCHOLOGY LA English DT Article DE Cognition; Personality; Reaction time; Sleep deprivation; State personality variables; Trait personality variables; Experiment ID PERFORMANCE; TASK AB The relationship between reaction time and both state and trait personality variables was investigated in 37 participants after 30 h of sleep deprivation. Regression analyses suggested that endorsement of greater Novelty Seeking, anger/hostility, and depression/dejection, and less confusion, was associated with greater reaction time declines on one Multi-Attribute Task Battery index after sleep deprivation. Further, greater Novelty Seeking and depression/dejection, and less vigor/activity, was associated with greater reaction time declines after sleep deprivation on another Multi-Attribute Task Battery index. Additional correlational analyses indicated that better reaction times were associated with greater Novelty Seeking and lower anger/hostility prior to sleep deprivation, and less confusion/bewilderment following sleep deprivation. Findings suggest that both state and trait personality variables are associated with reaction time performance following sleep deprivation. C1 [Carlozzi, Noelle E.] Kessler Fdn, Res Ctr, Outcomes & Assessment Lab, W Orange, NJ 07052 USA. [Horner, Michael David] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [Horner, Michael David; George, Mark S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Kose, Samet; Mishory, Alexander; Mu, Qiwen; Nahas, Ziad; Wells, Sarah A.; George, Mark S.] Brain Stimulat Lab, Charleston, SC USA. [Kose, Samet; Mishory, Alexander; Mu, Qiwen; Nahas, Ziad; Wells, Sarah A.; George, Mark S.] Ctr Adv Imaging Res, Charleston, SC USA. [Carlozzi, Noelle E.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Kose, Samet] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. [Yamanaka, Kaori] Showa Univ, Sch Med, Dept Neuropsychiat, Tokyo 142, Japan. RP Carlozzi, NE (reprint author), Kessler Fdn, Res Ctr, Outcomes & Assessment Lab, 1199 Pleasant Valley Way, W Orange, NJ 07052 USA. EM ncarlozzi@kesslerfoundation.org NR 20 TC 0 Z9 0 U1 4 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1046-1310 J9 CURR PSYCHOL JI Curr. Psychol. PD MAR PY 2010 VL 29 IS 1 BP 24 EP 33 DI 10.1007/s12144-009-9068-8 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 555FX UT WOS:000274495000003 ER PT J AU Centeno, CJ Schultz, JR Cheever, M Robinson, B Freeman, M Marasco, W AF Centeno, Christopher J. Schultz, John R. Cheever, Michelle Robinson, Brent Freeman, Michael Marasco, Wayne TI Safety and Complications Reporting on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells using Autologous Platelet Lysate Technique SO CURRENT STEM CELL RESEARCH & THERAPY LA English DT Review DE Mesenchymal stem cell; mesenchymal stem cells; platelet lysate; complications; safety; orthopedic; orthopedics; culture expansion AB Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of MSCs, showing their capabilities for differentiating into orthopedic tissues such as muscle, bone, cartilage, and tendon. However, the complication rate for autologous MSC therapy is only now beginning to be reported. Methods: Between 2005 and 2009, two groups of patients were treated for various orthopedic conditions with culture-expanded, autologous, bone marrow-derived MSCs (group 1: n=45; group 2: n=182). Cells were cultured in monolayer culture flasks using an autologous platelet lysate technique and re-injected into peripheral joints (n=213) or into intervertebral discs (n=13) with use of c-arm fluoroscopy. While both groups had prospective surveillance for complications, Group 1 additionally underwent 3.0T MRI tracking of the re-implant sites. Results: Mean follow-up from the time of the re-implant procedure was 10.6 +/- 7.3 months. Serial MRI's at 3 months, 6 months, 1 year and 2 years failed to demonstrate any tumor formation at the re-implant sites. Formal disease surveillance for adverse events based on HHS criteria documented 7 cases of probable procedure-related complications (thought to be associated with the re-implant procedure itself) and three cases of possible stem cell complications, all of which were either self-limited or were remedied with simple therapeutic measures. One patient was diagnosed with cancer; however, this was almost certainly unrelated to the MSC therapy. Conclusions: Using both high field MRI tracking and general surveillance in 227 patients, no neoplastic complications were detected at any stem cell re-implantation site. These findings are consistent with other reports that also show no evidence of malignant transformation in vivo, following implantation of MSCs that were expanded in vitro for limited periods. C1 [Centeno, Christopher J.; Schultz, John R.; Robinson, Brent] Centeno Schultz Clin, Broomfield, CO USA. [Cheever, Michelle; Robinson, Brent] Regenerat Sci LLC, Broomfield, CO USA. [Robinson, Brent] Centeno Schultz Clin, Vail, CO USA. [Freeman, Michael] Oregon Hlth & Sci Univ, Sch Med, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Marasco, Wayne] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Marasco, Wayne] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Robinson, B (reprint author), Centeno Schultz Clin, Broomfield, CO USA. EM centenooffice@centenoclinic.com OI Freeman, Michael/0000-0003-0228-3158 NR 43 TC 66 Z9 72 U1 0 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1574-888X J9 CURR STEM CELL RES T JI Curr. Stem Cell Res. Ther. PD MAR PY 2010 VL 5 IS 1 BP 81 EP 93 DI 10.2174/157488810790442796 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA V22GB UT WOS:000208262600011 PM 19951252 ER PT J AU Sailhamer, EA Li, YQ Smith, EJ Liu, BL Shuja, F Soupir, CP DeMoya, MA Velmahos, GC Alam, HB AF Sailhamer, Elizabeth A. Li, Yongqing Smith, Eleanor J. Liu, Baoling Shuja, Fahad Soupir, Chad P. DeMoya, Marc A. Velmahos, George C. Alam, Hasan B. TI Hypoxic "second hit" in leukocytes from trauma patients: Modulation of the immune response by histone deacetylase inhibition SO CYTOKINE LA English DT Article DE Histone acetylation; Hemorrhagic shock; Hypoxia; Inflammation; Histone deacetylase inhibitor ID CARDIAC HISTONES; RESUSCITATION STRATEGIES; SYSTEMIC INFLAMMATION; FLUID RESUSCITATION; HEMORRHAGIC-SHOCK; ACETYLATION; HIF-1-ALPHA; EXPRESSION; APOPTOSIS; CYTOKINES AB Introduction: Histone deacetylase inhibitors (HDACI), can improve survival after lethal hemorrhagic shock, and modulate the inflammatory response after hemorrhage/lipopolysaccharide (LPS). The current experiments were designed to study the effects of HDACI after hemorrhage and severe hypoxia. Methods: Splenic leukocytes from trauma and non-trauma patients (n = 4-5/group) were exposed to severe hypoxia with/without suberoylanilide hydroxamic acid (SAHA, 400 nM) for 8 h. Cytokines were measured by ELISA and RT-PCR, and hypoxia inducible factor (HIF)-1a and heme oxygenase (HO)-1 by Western blot. Results: After hemorrhage and hypoxia, SAHA increased IL-1b gene (4.7 +/- 1.2-fold) and protein expression (2.1 +/- 0.6-fold) in trauma splenic leukocytes. It also reduced IL-10 gene expression (0.6 +/- 0.2-fold), but did not alter TNFa or IL-6 levels. This unexpected pro-inflammatory response may be due to a decrease in HIF-1a and HO-1 protein levels. Conclusions: In this model of severe hypoxia, treatment with SAHA increased the inflammatory response in trauma leukocytes, possibly through inhibition of the HIFI /HO-1 pathway. Splenic leukocytes from non-trauma patients were variably affected by SAHA. Taken in context with the known anti-inflammatory properties of HDACI after hemorrhage/LPS, these findings suggest that the immune-modulating functions of HDACI are dependent on the type and severity of both the priming injury and subsequent insult. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Sailhamer, Elizabeth A.; Li, Yongqing; Smith, Eleanor J.; Liu, Baoling; Shuja, Fahad; DeMoya, Marc A.; Velmahos, George C.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Sch Med,Dept Surg, Boston, MA 02114 USA. [Soupir, Chad P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Div Hematopathol, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Sch Med,Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org FU Defense Advanced Research Projects Agency (DARPA); NRSA at NIH/NIGMS [1732 GM79880]; Scholars in Clinical Science Program at the Harvard Medical School; Polsky family FX Funded by a grant from the Defense Advanced Research Projects Agency (DARPA) to Dr. Alam. Dr. Sailhamer was supported by a NRSA postdoctoral fellowship (1732 GM79880) at NIH/NIGMS, and the Scholars in Clinical Science Program at the Harvard Medical School. Additional funds provided through a generous donation by the Polsky family. NR 34 TC 4 Z9 4 U1 1 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAR PY 2010 VL 49 IS 3 BP 303 EP 311 DI 10.1016/j.cyto.2009.11.013 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 566ER UT WOS:000275353400011 PM 20056553 ER PT J AU Dzik, WH Cserti-Gazdewich, CM Ssewanyana, I DeLelys, M Preffer, FI AF Dzik, W. H. Cserti-Gazdewich, C. M. Ssewanyana, I. DeLelys, M. Preffer, F. I. TI When Monocytes and Platelets Compete: the Effect of Platelet Count on the Flow Cytometric Measurement of Monocyte CD36 SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE CD36; platelet; monocyte; malaria; lipid; flow cytometry ID PLASMODIUM-FALCIPARUM MALARIA; SCAVENGER RECEPTOR CD36; GLYCOPROTEIN-IV; EXPRESSION; DEFICIENCY; DISEASE; HEART; NAKA AB Background: Flow cytometric measurement of monocyte surface CD36 is relevant to several conditions including diabetes, cardiovascular disease, lipid disorders, platelet isoimmunization, and susceptibility to P falciparum malaria. CD36 is also strongly expressed on platelets where it is also known as platelet glycoprotein IV. Methods: Whole blood samples, containing identical monocyte concentrations, were adjusted to contain platelets ranging from 20,000/uL to 600,000/uL, were stained with fluorescent-labeled anti-CD36, and analyzed by flow cytometry. Results: CD36 median fluorescent intensity (MFI) observed on monocytes decreased as the platelet concentration in the sample increased with more than a 50% decline in monocyte MFI over the normal range of platelet values. The effect was not abolished by using larger volumes of monoclonal antibody and was observed with different clones of reagent anti-CD36. The findings were most consistent with competition by platelets for the CD36 reagent. Similar findings were observed with antibody to class I HLA. Under defined assay conditions, monocyte CD36 MFI declined with rising platelet concentration in a predictable fashion following an inverse linear relationship. Conclusions: Measurement of CD36 expression on monocytes by flow cytometry in whole blood samples is affected by the sample platelet count. When comparing the monocyte CD36 expression among different individuals, our approach can be used to adjust measured monocyte CD36 expression for the effect of the platelet concentration in the sample. Competition by platelets for monoclonal reagents may occur in other settings when whole blood assays are used and when the target antigen is strongly expressed on both platelets and leukocytes. (C) 2009 Clinical Cytometry Society C1 [Dzik, W. H.; DeLelys, M.; Preffer, F. I.] Harvard Univ, Blood Transfus Serv, Massachusetts Gen Hosp, Med Sch,Dept Pathol, Boston, MA 02114 USA. [Cserti-Gazdewich, C. M.] Univ Hlth Network, Dept Transfus Med, Toronto, ON M5G 2C4, Canada. [Cserti-Gazdewich, C. M.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. [Ssewanyana, I.] Joint Clin Res Ctr, Kampala, Uganda. RP Dzik, WH (reprint author), Harvard Univ, Blood Transfus Serv, Massachusetts Gen Hosp, Med Sch,Dept Pathol, J-224,55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org NR 22 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD MAR PY 2010 VL 78B IS 2 BP 81 EP 87 DI 10.1002/cyto.b.20504 PG 7 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 578BE UT WOS:000276267500002 PM 19902557 ER PT J AU Marx, BP Foley, KM Feinstein, BA Wolf, EJ Kaloupek, DG Keane, TM AF Marx, Brian P. Foley, Kristen M. Feinstein, Brian A. Wolf, Erika J. Kaloupek, Danny G. Keane, Terence M. TI COMBAT-RELATED GUILT MEDIATES THE RELATIONS BETWEEN EXPOSURE TO COMBAT-RELATED ABUSIVE VIOLENCE AND PSYCHIATRIC DIAGNOSES SO DEPRESSION AND ANXIETY LA English DT Article DE abusive violence; guilt; posttraumatic stress disorder; major depressive disorder; veterans ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMA-RELATED GUILT; VIETNAM VETERANS; CAUSAL MODEL; PTSD; PERPETRATORS; VALIDATION; ATROCITIES; INVENTORY; SEVERITY AB Background: This study examined the degree to which combat-related guilt mediated the relations between exposure to combat-related abusive violence and both Posttraumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) in Vietnam Veterans. Methods: Secondary analyses were conducted on data collected from, 1,323 male Vietnam Veterans as part of a larger, multisite study. Results: Results revealed that combat-related guilt partially mediated the association between exposure to combat-related abusive violence and PTSD, but completely mediated the association with MDD, with overall combat exposure held constant in the model. Follow-up analyses showed that, when comparing those participants who actually participated in combat-related abusive violence with those who only observed it, combat-related guilt completely mediated the association between participation in abusive violence and both PTSD and MDD. Moreover, when comparing those participants who observed combat-related abusive violence with those who bad no exposure at all to it, combat-related guilt completely mediated the association between observation of combat-related abusive violence and MDD, but only partially mediated the association with PTSD. Conclusions: These findings suggest that guilt may be a mechanism through which abusive violence is related to PTSD and MDD among combat-deployed Veterans. These findings also suggest the importance of assessing abusive-violence related guilt among combat-deployed Veterans and implementing relevant interventions for such guilt whenever indicated. Depression and Anxiety 27:287-293, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Marx, Brian P.; Wolf, Erika J.; Kaloupek, Danny G.; Keane, Terence M.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. [Marx, Brian P.; Foley, Kristen M.; Feinstein, Brian A.; Wolf, Erika J.; Kaloupek, Danny G.; Keane, Terence M.] VA Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Marx, Brian P.; Kaloupek, Danny G.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst, Psychol Serv, Psychol 116B-4,150 S Huntington Ave, Boston, MA 02130 USA. EM brian.marx@va.gov OI Kaloupek, Danny/0000-0002-0795-593X; Wolf, Erika/0000-0003-2666-2435 NR 43 TC 19 Z9 19 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAR PY 2010 VL 27 IS 3 BP 287 EP 293 DI 10.1002/da.20659 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 563BU UT WOS:000275101400009 PM 20099268 ER PT J AU Sun, Q van Dam, RM Meigs, JB Franco, OH Mantzoros, CS Hu, FB AF Sun, Qi van Dam, Rob M. Meigs, James B. Franco, Oscar H. Mantzoros, Christos S. Hu, Frank B. TI Leptin and Soluble Leptin Receptor Levels in Plasma and Risk of Type 2 Diabetes in US Women A Prospective Study SO DIABETES LA English DT Article ID TOTAL-ENERGY INTAKE; INSULIN-RESISTANCE; REPLACEMENT THERAPY; METABOLIC SYNDROME; BOUND FRACTION; BODY-WEIGHT; OBESE GENE; ADIPONECTIN; SENSITIVITY; POPULATION AB OBJECTIVE-We prospectively examined plasma levels of leptin and soluble leptin receptor (sOB-R), as well as their interactions with other diabetes risk factors, in relation to type 2 diabetes to elucidate the complex relation between these two biomarkers and diabetes risk. RESEARCH DESIGN AND METHODS-Of 32,826 Nurses' Health Study participants who provided blood samples (luring 1989-1990, 1,054 incident case subjects of type 2 diabetes were identified and confirmed during 1990-2004 and 1,254 matched control subjects were selected. Plasma leptin and sOB-R levels were measured among these participants. RESULTS-Aft,er multivariate adjustment for BMI, lifestyle practices, and dietary factors, sOB-R levels were significantly associated with a lower risk of type 2 diabetes. In comparison with women in the lowest, quintile, the ORs (95% CI) of developing type 2 diabetes were 0.73 (0.55-0.96), 0.51 (0.38-0.68), 0.42 (0.31-0.57), and 0.39 (0.28-0.54; P for trend < 0.0001) for women in the second to fifth quintiles of sOB-R levels, respectively. In contrast, plasma leptin levels were not significantly associated with the risk of type 2 diabetes: The OR (95% CI) was 0.82 (0.62-1.10; P for trend = 0.46) comparing the highest with the lowest quintile of leptlin levels. sOB-R levels were consistently associated with a decreased risk of type 2 diabetes at various levels of leptin or high-molecular-weight adiponectin. CONCLUSIONS-These data suggest a strong inverse association between plasma sOB-R levels and risk of type 2 diabetes, independent of BMI, leptin, and adiponectin levels. Diabetes 59: 611-618, 2010 C1 [Sun, Qi; van Dam, Rob M.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [van Dam, Rob M.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [van Dam, Rob M.; Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Franco, Oscar H.] Univ Warwick, Hlth Sci Res Inst, Coventry CV4 7AL, W Midlands, England. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. RP Sun, Q (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM qisun@hsph.harvard.edu RI van Dam, Rob/F-9674-2010 OI van Dam, Rob/0000-0002-7354-8734 FU National Institutes of Health and the Intramural Research Program of the National Institute of Child Health & Human Development [CA-87969, DK-58845, DK-58785]; Unilever Postdoctoral Fellowship; American Diabetes Association; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK-080140]; Tanita Corporation; Beth Israel Deaconess Medical Center FX This work was supported by the National Institutes of Health and the Intramural Research Program of the National Institute of Child Health & Human Development (Grants CA-87969, DK-58845, and DK-58785). Q.S. was supported by a Unilever Postdoctoral Fellowship. J.B.M. was supported by a Career Development Award from the American Diabetes Association and Grant K24 DK-080140 from the National Institute of Diabetes and Digestive and Kidney Diseases. C.S.M. was supported by discretionary grants from the Tanita Corporation and Beth Israel Deaconess Medical Center.; J.B.M. currently has research grants from GlaxoSmithKline and sanofi-aventis and has served on consultancy boards for sanofi-aventis and Interleukin Genetics. No other potential conflicts of interest relevant to this article were reported.; Parts of this study were presented in abstract form at the Scientific Sessions of the American Heart Association, Orlando, Florida, 14-18 November 2009. NR 53 TC 43 Z9 48 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2010 VL 59 IS 3 BP 611 EP 618 DI 10.2337/db09-1343 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 568YQ UT WOS:000275562900008 PM 19959759 ER PT J AU Stone, RA Rao, RH Sevick, MA Cheng, CR Hough, LJ Macpherson, DS Franko, CM Anglin, RA Obrosky, DS DeRubertis, FR AF Stone, Roslyn A. Rao, R. Harsha Sevick, Mary Ann Cheng, Chunrong Hough, Linda J. Macpherson, David S. Franko, Carol M. Anglin, Rebecca A. Obrosky, D. Scott DeRubertis, Frederick R. TI Active Care Management Supported by Home Telemonitoring in Veterans With Type 2 Diabetes The DiaTel randomized controlled trial SO DIABETES CARE LA English DT Article ID BLOOD-GLUCOSE CONTROL; GLYCEMIC CONTROL; COMPLICATIONS; INSULIN; METAANALYSIS; THERAPY; COSTS AB OBJECTIVE - We compared the short-term efficacy of home telemonitoring coupled with active medication management by a nurse practitioner with a monthly care coordination telephone call on glycemic control in veterans with type 2 diabetes and entry A1C >= 7.5%. RESEARCH DESIGN AND METHODS - Veterans who received primary care at the VA Pittsburgh Healthcare System from June 2004 to December 2005, who were taking oral hypoglycemic agents and/or insulin for >= 1 year, and who had A1C >= 7.5% at enrollment were randomly assigned to either active care management with home telemonitoring (ACM+HT group, n = 73) or a monthly care coordination telephone call (CC group, n = 77). Both groups received monthly calls for diabetes education and self-management review. ACM+HT group participants transmitted blood glucose, blood pressure, and weight to a nurse practitioner using the Viterion 100 TeleHealth Monitor; the nurse practitioner adjusted medications for glucose, blood pressure, and lipid control based on established American Diabetes Association targets. Measures were obtained at baseline, 3-month, and 6-month visits. RESULTS - Baseline characteristics were similar in both groups, with mean A1C of 9.4% (CC group) and 9.6% (ACM+HT group). Compared with the CC group, the ACM+HT group demonstrated significantly larger decreases in A1C at 3 months (1.7 vs. 0.7%) and 6 months (1.7 vs. 0.8%; P < 0.001 for each), with most improvement occurring by 3 months. CONCLUSIONS - Compared with the CC group, the ACM + HT group demonstrated significantly greater reductions in A1C by 3 and 6 months. However, both interventions improved glycemic control in primary care patients with previously inadequate control. C1 [Rao, R. Harsha; Anglin, Rebecca A.; DeRubertis, Frederick R.] VA Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. [Stone, Roslyn A.; Cheng, Chunrong] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Stone, Roslyn A.; Sevick, Mary Ann; Cheng, Chunrong] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Rao, R. Harsha; Sevick, Mary Ann; Macpherson, David S.; Obrosky, D. Scott; DeRubertis, Frederick R.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Sevick, Mary Ann; Franko, Carol M.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Sevick, Mary Ann] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Hough, Linda J.] Vet Res Fdn Pittsburgh, Pittsburgh, PA USA. [Macpherson, David S.] VISN 4 Healthcare Network, Pittsburgh, PA USA. RP DeRubertis, FR (reprint author), VA Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. EM frederick.derubertis@va.gov FU U.S. Air Force [W81XWH-04-2-0030] FX This work was supported by award W81XWH-04-2-0030 from the U.S. Air Force, administered by the U.S. Army Medical Research Acquisition Activity, Fort Detrick, Maryland, and by resources and the use of facilities at the VAPHS. NR 24 TC 75 Z9 78 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2010 VL 33 IS 3 BP 478 EP 484 DI 10.2337/dc09-1012 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 568YO UT WOS:000275562700005 PM 20009091 ER PT J AU Markowitz, JT Butler, DA Volkening, LK Antisdel, JE Anderson, BJ Laffel, LMB AF Markowitz, Jessica T. Butler, Deborah A. Volkening, Lisa K. Antisdel, Jeanne E. Anderson, Barbara J. Laffel, Lori M. B. TI Brief Screening Tool for Disordered Eating in Diabetes Internal consistency and external validity in a contemporary sample of pediatric patients with type 1 diabetes SO DIABETES CARE LA English DT Article ID BODY DISSATISFACTION; ADOLESCENTS; WOMEN; MELLITUS; FEMALES; PREVALENCE; MORTALITY; BEHAVIOR; HABITS; WEIGHT AB OBJECTIVE - To update and validate a diabetes-specific screening tool for disordered eating (the Diabetes Eating Problem Survey [DEPS]) in contemporary youth with type I diabetes. RESEARCH DESIGN AND METHODS - A total of 112 youth with type 1 diabetes, ages 13-19 years, completed the DEPS. Higher scores on the DEPS indicate more disordered eating behaviors. Youth and their parents also completed additional surveys to examine diabetes-specific family conflict, negative affect related to blood glucose monitoring, youth quality of life, and diabetes burden, Clinicians provided data on height, weight, A1C, and insulin dosing. The DEPS was revised into a shorter, updated measure and validated. RESULTS - The revised 16-item DEPS (DEPS-R) displayed excellent internal consistency (Cronbach's alpha = 0.86). Construct validity was demonstrated by positive correlations with zBMI (P = 0.01), A1C (P = 0.001), diabetes-specific family conflict (P < O 005), Youth negative affect around blood glucose monitoring (P = 0.001), parental diabetes-specific burden (P = O 0005), and negative correlations With frequency of blood glucose monitoring (P = 0.03) and quality of life (P <= 0.002). External Validity was confirmed against clinician report of insulin restriction. CONCLUSIONS - The DEPS-R is a 16-item diabetes-specific self-report measure of disordered eating that can be completed in < 10 min. It demonstrated excellent internal consistency, construct validity, and external validity in this contemporary sample of youth with type 1 diabetes, Future Studies should focus on using the DEPS-R to identify high-risk populations for prevention of and early intervention for disordered eating behaviors. C1 [Markowitz, Jessica T.; Butler, Deborah A.; Volkening, Lisa K.; Laffel, Lori M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Markowitz, Jessica T.; Butler, Deborah A.; Volkening, Lisa K.; Laffel, Lori M. B.] Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. [Antisdel, Jeanne E.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Anderson, Barbara J.] Texas Childrens Hosp, Baylor Coll Med, Psychol Sect, Houston, TX 77030 USA. [Anderson, Barbara J.] Texas Childrens Hosp, Baylor Coll Med, Endocrinol Sect, Houston, TX 77030 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU National Institutes of Health Training [T32 DK007260]; National Institute of Diabetes and Digestive and Kidney Diseases [DK-46887]; Charles H. Hood Foundation; Maria Griffin Drury Pediatric Fund; Katherine Adler Astrove Youth Education Fund; Diabetes and Endocrinology Research Center [P30DK036836] FX This work was supported in part by National Institutes of Health Training Grant T32 DK007260, National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-46887, the Charles H. Hood Foundation, the Maria Griffin Drury Pediatric Fund, the Katherine Adler Astrove Youth Education Fund, and the Diabetes and Endocrinology Research Center (P30DK036836). NR 25 TC 44 Z9 44 U1 2 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2010 VL 33 IS 3 BP 495 EP 500 DI 10.2337/dc09-1890 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 568YO UT WOS:000275562700008 PM 20032278 ER PT J AU Brownstein, JS Murphy, SN Goldfine, AB Grant, RW Sordo, M Gainer, V Colecchi, JA Dubey, A Nathan, DM Glaser, JP Kohane, IS AF Brownstein, John S. Murphy, Shawn N. Goldfine, Allison B. Grant, Richard W. Sordo, Margarita Gainer, Vivian Colecchi, Judith A. Dubey, Anil Nathan, David M. Glaser, John P. Kohane, Isaac S. TI Rapid Identification of Myocardial Infarction Risk Associated With Diabetes Medications Using Electronic Medical Records SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR OUTCOMES; ROSIGLITAZONE; PIOGLITAZONE; EVENTS; THIAZOLIDINEDIONES; METAANALYSIS; DATABASE; DEATH AB OBJECTIVE - To assess the ability to identify potential association(s) of diabetes medications with myocardial infarction using usual care clinical data obtained from the electronic medical record. RESEARCH DESIGN AND METHODS - We defined a retrospective cohort of patients (m = 34,253) treated with a sulfonylurea, metformin, rosiglitazone, or pioglitazone in a single academic health care network. All patients were aged >18 years with at least one prescription for one of the medications between I January 2000 and 31. December 2006. The Study Outcome was acute myocardial infarction requiring hospitalization. We used a cumulative temporal approach to ascertain the calendar date for earliest identifiable risk associated with rosiglitazone compared with that for other therapies. RESULTS - Sulfonylurea, metformin, rosiglitazone, Or pioglitazone therapy was prescribed for 11,200, 12,490, 1,879, and 806 patients, respectively. A total of 1,343 myocardial infarctions were identified. After adjustment for potential myocardial infarction risk factors, the relative risk for myocardial infarction With rosiglitazone was 1.3 (95% Cl 1.1-1.6) compared With sulfonylurea, 2.2 (1.6-3.1) compared With metformin, and 2.2 (1.5-3.4) compared with pioglitazone. Prospective surveillance using these data would have identified increased risk for myocardial infarction With rosiglitazone compared with metformin within 18 months of its introduction with a risk ratio of 2.1 (95% Cl 1.2-3.8). CONCLUSIONS - our results are consistent with a relative adverse cardiovascular risk profile for rosiglitazone. Our use of usual care electronic data sources from a large hospital network represents an innovative approach to rapid safety signal detection that may enable more effective postmarketing drug surveillance. C1 [Brownstein, John S.; Kohane, Isaac S.] Childrens Hosp, Informat Program, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. [Brownstein, John S.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Brownstein, John S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Murphy, Shawn N.; Sordo, Margarita; Dubey, Anil] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Murphy, Shawn N.; Goldfine, Allison B.; Sordo, Margarita; Gainer, Vivian; Colecchi, Judith A.; Dubey, Anil; Glaser, John P.; Kohane, Isaac S.] Partners Healthcare, Boston, MA USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Grant, Richard W.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Grant, Richard W.; Nathan, David M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Kohane, Isaac S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Brownstein, JS (reprint author), Childrens Hosp, Informat Program, Harvard Mit Div Hlth Sci & Technol, 300 Longwood Ave, Boston, MA 02115 USA. EM john_brownstein@harvard.edu RI Kohane, Isaac Kohane/K-3716-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Grant, Richard/0000-0002-6164-8025 FU National Institutes of Health National Center for Biomedical Computing [5U54-LM-008748] FX This work was supported in part by the National Institutes of Health National Center for Biomedical Computing (Grant 5U54-LM-008748). NR 26 TC 39 Z9 40 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2010 VL 33 IS 3 BP 526 EP 531 DI 10.2337/dc09-1506 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 568YO UT WOS:000275562700015 PM 20009093 ER PT J AU Sosenko, JM Palmer, JP Rafkin, LE Krischer, JP Cuthbertson, D Greenbaum, CJ Eisenbarth, G Skyler, JS AF Sosenko, Jay M. Palmer, Jerry P. Rafkin, Lisa E. Krischer, Jeffrey P. Cuthbertson, David Greenbaum, Carla J. Eisenbarth, George Skyler, Jay S. CA Diabet Prevention Trial-Type TI Trends of Earlier and Later Responses of C-peptide to Oral Glucose Challenges With Progression to Type 1 Diabetes in Diabetes Prevention Trial-Type 1 Participants SO DIABETES CARE LA English DT Article ID INSULIN-RESPONSE; TRIAL-TYPE-1; PREDICTION; TOLERANCE AB OBJECTIVE - We studied the C-peptide response to oral glucose with progression to type I diabetes in Diabetes Prevention Trial-Type 1 (DPT-1) participants. RESEARCH DESIGN AND METHODS - Among 504 DPT-1 participants <15 years of age, longitudinal analyses were performed in 36 progressors and 80 nonprogressors. Progressors had oral glucose tolerance tests (OGTTs) at baseline and every 6 months from 2.0 to 0.5 years before diagnosis; nonprogressors had OGTTs over similar intervals before their last Visit. Sixty-six progressors and 192 nonprogressors were also studied proximal to and at diagnosis. RESULTS - The 30-0 min C-peptide difference from OGTTs performed 2.0 years before diagnosis in progressors was lower than the 30-0 min C-peptide difference from OGTTs performed 2.0 years before the last visit in nonprogressors(P < 0.01) and remained lower overtime. The 90-60 min C-peptide difference was positive at every OGTT before diagnosis in progressors, whereas it was negative at every OGTT before the last Visit in nonprogressors (P < 0.01 at 2.0 years). The percentage whose peak C-peptide occurred at 120 min was higher in progressors at 2.0 years (P < 0.05); this persisted over time (P < 0.001 at 0.5 years). However, the peak C-peptide levels were only significantly lower at 0.5 years in progressors (P < 0.01). The timing of the peak C-peptide predicted type 1 diabetes (P < 0.001); peak C-peptide levels were less predictive (P < 0.05). CONCLUSIONS - A decreased early C-peptide response to oral glucose and an increased later response occur at least 2 years before the diagnosis of type 1 diabetes. C1 [Sosenko, Jay M.; Rafkin, Lisa E.; Skyler, Jay S.] Univ Miami, Div Endocrinol, Miami, FL USA. [Palmer, Jerry P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Palmer, Jerry P.] Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Krischer, Jeffrey P.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA. [Cuthbertson, David] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. [Greenbaum, Carla J.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. [Eisenbarth, George] Univ Colorado, HLA DNA Lab, Aurora, CO USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016 FU NIDDK NIH HHS [U01 DK061034] NR 12 TC 20 Z9 20 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2010 VL 33 IS 3 BP 620 EP 625 DI 10.2337/dc09-1770 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 568YO UT WOS:000275562700033 PM 20032282 ER PT J AU Thadhani, R Powe, CE Tjoa, ML Khankin, E Ye, J Ecker, J Schneyer, A Karumanchi, SA AF Thadhani, Ravi Powe, Camille E. Tjoa, May Lee Khankin, Eliyahu Ye, Jun Ecker, Jeffrey Schneyer, Alan Karumanchi, S. Ananth TI First-Trimester Follistatin-Like-3 Levels in Pregnancies Complicated by Subsequent Gestational Diabetes Mellitus SO DIABETES CARE LA English DT Article ID ACTIVIN-A; INSULIN-RESISTANCE; MYOSTATIN; SECRETION; OUTCOMES; GLUCOSE; BINDING; ALPHA; WOMEN AB OBJECTIVE - To determine whether maternal levels of follistatin-like-3 (FSTL3), an inhibitor of activin and myostatin involved in glucose homeostasis, are altered in the first trimester of pregnancies Complicated by subsequent gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS - This was a nested case-control Study of subjects enrolled in a prospective cohort of pregnant women with and without GDM (>= 2 abnormal values on a 100-g glucose tolerance test at similar to 28 weeks of gestation). We measured FSTL3 levels in serum collected during the first trimester of pregnancy. Logistic regression analyses were used to determine the risk of GDM. RESULTS - Women who developed GDM (n = 37) had lower first-trimester serum levels of FSTL3 compared with women who did not (n = 127) (median 10,789 [interquartile range 7,013-18,939] vs. 30,670 [18,370-55,484] pg/ml, P < 0.001.). When subjects were divided into tertiles based on FSTL3 levels, women With the lowest levels demonstrated a marked increase in risk for developing GDM in univariate (odds ratio 11.2 [95% CI 3.6-35.3]) and multivariate (14.0 [4.1-47.9]) analyses. There was a significant negative correlation between first-trimester FSTL3 levels and similar to 28-week nonfasting glucose levels (r = -0.30, P < 0.001). CONCLUSIONS - First-trimester FSTL3 levels are associated with glucose intolerance and GDM later in pregnancy. C1 [Thadhani, Ravi; Powe, Camille E.; Ye, Jun] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Thadhani, Ravi; Powe, Camille E.; Tjoa, May Lee; Khankin, Eliyahu; Ye, Jun; Ecker, Jeffrey; Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tjoa, May Lee; Khankin, Eliyahu; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Tjoa, May Lee; Khankin, Eliyahu; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Ecker, Jeffrey] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Schneyer, Alan] Univ Massachusetts, Pioneer Valley Life Sci Inst, Springfield, MA USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. EM rthadhani@partners.org RI Khankin, Eli/M-7648-2013 FU Beckman Coulter; Howard Hughes Medical Institute FX This Study was partially funded by a research grant from Beckman Coulter (to R.T.). C.E.P. is a Howard Hughes Medical Institute Medical Research Training Fellow. S.A.K. is an investigator of the Howard Hughes Medical Institute. NR 25 TC 22 Z9 22 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2010 VL 33 IS 3 BP 664 EP 669 DI 10.2337/dc09-1745 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 568YO UT WOS:000275562700041 PM 20007937 ER PT J AU Mensing, C AF Mensing, Carole TI Comparing the Processes Accreditation and Recognition SO DIABETES EDUCATOR LA English DT Article ID DIABETES SELF-MANAGEMENT; RANDOMIZED CONTROLLED-TRIAL; CHRONIC CARE MODEL; NATIONAL STANDARDS; EDUCATION; INTERVENTIONS; METAANALYSIS; ADULTS; EMPOWERMENT; OUTPATIENT AB Diabetes education programs are developed to serve the diabetes community by offering quality education that meets a set of standards and is then eligible for third-party insurance reimbursement. Three organizations are authorized by the U.S. Centers for Medicare and Medicaid Services to determine whether diabetes education programs meet required standards. Each of the three relies on the 2007 edition of the National Standards for Diabetes Self-Management Education. This article summarizes similarities among and unique qualities of each of the organization's approaches to assuring quality. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Mensing, C (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM carole.mensing@joslin.harvard.edu NR 31 TC 0 Z9 0 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAR-APR PY 2010 VL 36 IS 2 BP 219 EP + DI 10.1177/0145721710361390 PG 21 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 577ZG UT WOS:000276262000004 PM 20410368 ER PT J AU Egede, LE Osborn, CY AF Egede, Leonard E. Osborn, Chandra Y. TI Role of Motivation in the Relationship Between Depression, Self-care, and Glycemic Control in Adults With Type 2 Diabetes SO DIABETES EDUCATOR LA English DT Article ID FUNCTIONAL DISABILITY; COMORBID DEPRESSION; MAJOR DEPRESSION; METAANALYSIS; INDIVIDUALS; PREVALENCE; ADHERENCE; SYMPTOMS; QUESTIONNAIRE; ASSOCIATION AB Purpose The mechanism by which depression influences health outcomes in persons with diabetes is uncertain. The purpose of this study was to test whether depression is related to self-care behavior via social motivation and indirectly related to glycemic control via self-care behavior. Methods Patients with diabetes were recruited from an outpatient clinic. Information gathered pertained to demographics, depression, and diabetes knowledge (information); diabetes fatalism (personal motivation); social support (social motivation); and diabetes self-care (behavior). Hemoglobin A IC values were extracted from the patient medical record. Structural equation models tested the predicted pathways. Results Higher levels of depressive symptoms were significantly related to having less social support and decreased performance of diabetes self-care behavior. In addition, when depressive symptoms were included in the model, fatalistic attitudes were no longer associated with behavioral performance. Conclusions Among adults with diabetes, depression impedes the adoption of effective self-management behaviors (including physical activity, appropriate dietary behavior, foot care, and appropriate self-monitoring of blood glucose behavior) through a decrease in social motivation. C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Osborn, Chandra Y.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Osborn, Chandra Y.] Vanderbilt Univ, Sch Med, Vanderbilt Eskind Diabet Ctr, Diabet Res & Training Ctr, Nashville, TN 37212 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu FU Diversity Supplement Award (NIDDK) [P60 DK020593] FX Dr Osborn is supported by a Diversity Supplement Award (NIDDK P60 DK020593). NR 33 TC 39 Z9 42 U1 4 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAR-APR PY 2010 VL 36 IS 2 BP 276 EP 283 DI 10.1177/0145721710361389 PG 8 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 577ZG UT WOS:000276262000008 PM 20179250 ER PT J AU Bouatia-Naji, N Saxena, R Hivert, MF Langenberg, C Tanaka, T Pankow, J Vollenweider, P Lyssenko, V Levy-Marchal, C Sladek, R Pattou, F Watanabe, R Froguel, P AF Bouatia-Naji, N. Saxena, R. Hivert, M. F. Langenberg, C. Tanaka, T. Pankow, J. Vollenweider, P. Lyssenko, V. Levy-Marchal, C. Sladek, R. Pattou, F. Watanabe, R. Froguel, P. TI A meta-analysis of GWA blood glucose after 2 h of OGTT revealed that GIPR is associated with the secretion of insulin based on glucose and ADCY5 is a new susceptibility gene for type 2 diabetes. SO DIABETES & METABOLISM LA French DT Meeting Abstract C1 [Bouatia-Naji, N.; Froguel, P.] Inst Pasteur, Cnrs 8090, F-59019 Lille, France. [Saxena, R.] Masschusetts Gen Hosp, Cnrs 8090, Aucun Resultat, MA USA. [Hivert, M. F.] Massachusets Gen Hosp, Broad Inst Mit, Boston, MA USA. [Langenberg, C.] MRC, Epidemiol Unit, Cambridge, Grande Bretagne, England. [Tanaka, T.] Res Inst, Baltimore, MD USA. [Pankow, J.] Univ Minnesota, Minneapolis, MN USA. [Vollenweider, P.] CHU Vaudois, CH-1011 Lausanne, Switzerland. [Lyssenko, V.] Lund Univ, Ctr Diabet, Malmo, Sweden. [Levy-Marchal, C.] Hop Robert Debre, INSERM, U690, F-75019 Paris, France. [Sladek, R.] McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Pattou, F.] CHRU, INSERM, U859, Lille, France. [Watanabe, R.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. RI BOUATIA-NAJI, NABILA/D-5863-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 1262-3636 J9 DIABETES METAB JI Diabetes Metab. PD MAR PY 2010 VL 36 SI 1 BP A3 EP A3 DI 10.1016/S1262-3636(10)70014-8 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 575EJ UT WOS:000276049200012 ER PT J AU Egede, LE Ellis, C AF Egede, Leonard E. Ellis, Charles TI Diabetes and depression: Global perspectives SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Diabetes; Depression; Health care; Health outcomes; Global perspective ID PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; POOR GLYCEMIC CONTROL; MENTAL-HEALTH SURVEYS; QUALITY-OF-LIFE; PRIMARY-CARE; COMORBID DEPRESSION; RISK-FACTOR; SELF-CARE; MEDICATION ADHERENCE AB Background: Diabetes and depression are highly prevalent conditions and have significant impact on health outcomes. This study reviewed the literature on the prevalence, burden of illness, morbidity, mortality, and cost of comorbid depression in people with diabetes as well as the evidence on effective treatments. Methods: Systematic review of the literature on the relationship between diabetes and depression was performed. A comprehensive search of the literature was performed on Medline from 1966 to 2009. Studies that examined the association between diabetes and depression were reviewed. A formal meta-analysis was not performed because of the broad area covered and the heterogeneity of the studies. Instead, a qualitative aggregation of studies was performed. Results: Diabetes and depression are debilitating conditions that are associated with significant morbidity, mortality, and healthcare costs. Coexisting depression in people with diabetes is associated with decreased adherence to treatment, poor metabolic control, higher complication rates, decreased quality of life, increased healthcare use and cost, increased disability and lost productivity, and increased risk of death. Conclusion: The coexistence of diabetes and depression is associated with significant morbidity, mortality, and increased healthcare cost. Coordinated strategies for clinical care are necessary to improve clinical outcomes and reduce the burden of illness. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. [Egede, Leonard E.; Ellis, Charles] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Ellis, Charles] Med Univ S Carolina, Dept Hlth Profess, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK NIH HHS [R01 DK081121-01A1, R01 DK081121, R01 DK081121-02, R01 DK081121-03] NR 85 TC 150 Z9 164 U1 11 U2 30 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD MAR PY 2010 VL 87 IS 3 BP 302 EP 312 DI 10.1016/j.diabres.2010.01.024 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 580KH UT WOS:000276446600002 PM 20181405 ER PT J AU Renshaw, AA Auger, M Birdsong, G Cibas, ES Henry, M Hughes, JH Moriarty, A Tench, W Wilbur, DC Elsheikh, TM AF Renshaw, Andrew A. Auger, Manon Birdsong, George Cibas, Edmund S. Henry, Michael Hughes, Jonathan H. Moriarty, Ann Tench, William Wilbur, David C. Elsheikh, Tarik M. TI ASC/SIL Ratio for Cytotechnologists: A Survey of its Utility in Clinical Practice SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE ASC to SIL ratio; gynecological cytology; quality control; diagnostic accuracy ID INTERLABORATORY COMPARISON PROGRAM; CURRENT LABORATORY PRACTICES; ATYPICAL SQUAMOUS CELLS; QUALITY-CONTROL; UNDETERMINED SIGNIFICANCE; CERVICOVAGINAL CYTOLOGY; PAPANICOLAOU SMEARS; PERFORMANCE; PARTICIPANTS AB The atypical squamous Cell to squamous intraepithelial lesion (ASC/SIL) ratio for cytotechnologists (CTs) may, correlate with screening sensitivity in some labotatory settings Whether this ratio can be applied to other laboratory settings is not known We conducted a survey of nine cytology laboratories and correlated the ASC/SIL ratio of individual CTs with other laboratory characteristics The ASC/SIL ratio for individual CTs varied from 0.6 to 4.5 (mean 19, median 15) The ASC/SIL ratio within individual laboratories varied up to 567%, 25/78 932%) CTs had an ASC/SIL ratio of less than 15, though only three of nine laboratories had more than one CT with a ratio this low Laboratories that used 100% location guided screening (ThinPrep Imaging System) were much less likely to have a CT with a ratio <15 (1/20, 5%) than laboratories that never used location guided screening (14/34, 42%, P = 0.004). In addition, the normalized variance of these same laboratories that used location guided screening was significantly lower than those that did not (normalized standard deviation 0.32 vs 0.55, P = 0.004) The ASC/SIL ratios did not correlate with laboratory volume, individual workload, or type of specimen preparation (conventional vs liquid based) The ASC/SIL ratio for CTs varies widely between and within laboratories, and may correlate with the use of location guided screening. Very low ASC/SIL ratios are unusual, and CTs with low ratios may warrant further evaluation Diagn. Cytopathol 2010:38:180-183 (C) 2009 Wiley-Liss, Inc C1 [Renshaw, Andrew A.] Baptist Hosp Miami, Dept Pathol, Miami, FL 33176 USA. [Auger, Manon] McGill Univ, Dept Pathol, Ctr Hlth, Montreal, PQ, Canada. [Birdsong, George] Grady Mem Hosp, Dept Pathol, Atlanta, GA 30335 USA. [Cibas, Edmund S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Henry, Michael] Mayo Clin, Dept Pathol, Rochester, MN USA. [Hughes, Jonathan H.] Lab Med Consultants Ltd, Las Vegas, NV USA. [Moriarty, Ann] Ameripath Indiana, Dept Pathol, Indianapolis, IN USA. [Tench, William] Palomar Med Ctr, Dept Pathol, Escondido, CA USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Elsheikh, Tarik M.] Ball Mem Hosp, PA Labs, Muncie, IN 47303 USA. RP Renshaw, AA (reprint author), Baptist Hosp Miami, Dept Pathol, 8900 N Kendall Dr, Miami, FL 33176 USA. NR 14 TC 5 Z9 6 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD MAR PY 2010 VL 38 IS 3 BP 180 EP 183 DI 10.1002/dc.21167 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 569WJ UT WOS:000275633200005 PM 19760762 ER PT J AU Restrepo, MI Vasquez, EM Echeyerri, C Fiebelkorn, KR Anstead, GM AF Restrepo, Marcos I. Vasquez, E. Martin Echeyerri, Carolina Fiebelkorn, Kristin R. Anstead, Gregory M. TI Fibrin ring granulomas in Rickettsia typhi infection SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Rickettsia typhi; Murine typhus; Fever of unknown origin; Fibrin ring granuloma ID BONE-MARROW; Q-FEVER; MURINE TYPHUS; HEPATITIS-A; LIVER; PATIENT; DISEASE AB We describe a 71-year-old man hospitalized for fever and productive cough. Laboratory investigation showed anemia, thrombocytopenia, elevated transaminases, hyponatremia, and hypoalbuminemia. Computerized tomography of the abdomen, thorax, and sinuses, echocardiography, and a gallium scan did not reveal the source of the fever. The patient remained febrile despite courses of piperacillin tazobactam/azithromycin and ceftriaxone/vancomycin. A bone marrow biopsy showed fibrin ring granulomas, and 2 rickettsial serologic panels were positive for Rickettsia typhi infection and negative for Q fever. The patient was given doxycycline, and the fever resolved within 48 h. We propose that fibrin ring granulomas also occur in murine typhus. (C) 2010 Published by Elsevier Inc. C1 [Anstead, Gregory M.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA. [Anstead, Gregory M.] S Texas Vet Healthcare Syst, Dept Med, San Antonio, TX 78229 USA. [Fiebelkorn, Kristin R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Vasquez, E. Martin; Echeyerri, Carolina] Hosp Pablo Tobon Uribe, Medellin, Colombia. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm, Dept Med, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, Vet Evidence Res Disseminat & Implementat Ctr VER, San Antonio, TX 78229 USA. RP Anstead, GM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA. EM anstead@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 NR 30 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 EI 1879-0070 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD MAR PY 2010 VL 66 IS 3 BP 322 EP 325 DI 10.1016/j.diagmicrobio.2009.10.019 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 594YJ UT WOS:000277577000014 PM 20071129 ER PT J AU Zhu, A Kaneshiro, M Kaunitz, JD AF Zhu, Amy Kaneshiro, Marc Kaunitz, Jonathan D. TI Evaluation and Treatment of Iron Deficiency Anemia: A Gastroenterological Perspective SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE Clinical diagnosis; Micronutrient deficiencies; Red cell indices; Ferritin ID INFLAMMATORY-BOWEL-DISEASE; UPPER GASTROINTESTINAL-TRACT; RANDOMIZED CONTROLLED-TRIAL; RESTLESS LEGS SYNDROME; INTRAVENOUS IRON; SERUM FERRITIN; ORAL IRON; PREMENOPAUSAL WOMEN; CELIAC-DISEASE; CAPSULE-ENDOSCOPY AB A substantial volume of the consultations requested of gastroenterologists are directed towards the evaluation of anemia. Since iron deficiency anemia often arises from bleeding gastrointestinal lesions, many of which are malignant, establishment of a firm diagnosis usually obligates an endoscopic evaluation. Although the laboratory tests used to make the diagnosis have not changed in many decades, their interpretation has, and this is possibly due to the availability of extensive testing in key populations. We provide data supporting the use of the serum ferritin as the sole useful measure of iron stores, setting the lower limit at 100 mu g/l for some populations in order to increase the sensitivity of the test. Trends of the commonly obtained red cell indices, mean corpuscular volume, and the red cell distribution width can provide valuable diagnostic information. Once the diagnosis is established, upper and lower gastrointestinal endoscopy is usually indicated. Nevertheless, in many cases a gastrointestinal source is not found after routine evaluation. Additional studies, including repeat upper and lower endoscopy and often investigation of the small intestine may thus be required. Although oral iron is inexpensive and usually effective, there are many gastrointestinal conditions that warrant treatment of iron deficiency with intravenous iron. C1 [Kaunitz, Jonathan D.] W Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. [Zhu, Amy; Kaneshiro, Marc; Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Zhu, Amy; Kaneshiro, Marc] Cedars Sinai VA Residency Program, Los Angeles, CA USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU Department of Medicine, West Los Angeles VA Medical Center; Cedars-VA Residency Program FX This work was supported by the Department of Medicine, West Los Angeles VA Medical Center and the Cedars-VA Residency Program. We would like to thank Jenifer Kugler for her expert editorial assistance. NR 89 TC 40 Z9 44 U1 0 U2 13 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAR PY 2010 VL 55 IS 3 BP 548 EP 559 DI 10.1007/s10620-009-1108-6 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 556UD UT WOS:000274617500002 PM 20108038 ER PT J AU Huang, ES Gazelle, GS Hur, C AF Huang, Edward S. Gazelle, G. Scott Hur, Chin TI Consensus Guidelines in the Management of Branch Duct Intraductal Papillary Mucinous Neoplasm: A Cost-Effectiveness Analysis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE IPMN; Branch duct IPMN; Consensus guidelines; Cost effectiveness; Pancreatic cysts; Malignancy; Surgery ID SERVICES TASK-FORCE; TERM-FOLLOW-UP; NATURAL-HISTORY; CLINICOPATHOLOGICAL CHARACTERISTICS; SURGICAL-MANAGEMENT; UPDATED EXPERIENCE; 208 RESECTIONS; PANCREAS; TUMORS; CANCER AB Based on consensus guidelines, surgical resection of branch duct intraductal papillary mucinous neoplasm (BD-IPMN) is indicated in patients with symptoms of cyst size a parts per thousand yen30 mm, intramural nodules, or dilated main pancreatic duct greater than 6 mm. The aim of this study was to determine the cost effectiveness of consensus guideline implementation in the management of BD-IPMN. We developed a decision analytic model to compare the costs and effectiveness of three management strategies for a cohort of 60-year-old patients with branch duct IPMN: (1) surveillance using consensus guidelines for surgical resection (surveillance strategy), (2) surgical resection based on symptoms without surveillance (no surveillance strategy), and (3) immediate surgery (surgery strategy). The primary outcomes were quality-adjusted life years (QALYs), cost, and incremental cost-effectiveness ratio (ICER). Sensitivity analysis was performed over a wide ranges of estimates. The no surveillance strategy was the least costly, but also the least effective, while the surgery strategy was the most costly and most effective. Compared to the no surveillance strategy, the surveillance strategy cost an additional $20,096 per QALY. The incremental cost-effectiveness ratio of the surgery strategy compared with the surveillance strategy was $132,436 per QALY. In a probabilistic sensitivity analysis, if society was willing to pay $50,000 per quality-adjusted life year gained, then 88.1% of patients using the surveillance strategy would be within budget. Immediate surgery is the most effective, but may be prohibitively expensive. The surveillance strategy is a cost-effective option compared to no surveillance. C1 [Huang, Edward S.; Hur, Chin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Huang, Edward S.; Gazelle, G. Scott; Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Huang, Edward S.; Gazelle, G. Scott; Hur, Chin] Harvard Univ, Sch Med, Boston, MA USA. [Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Huang, ES (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 101 Merrimac St 10th Floor, Boston, MA 02114 USA. EM eshuang@partners.org OI Hur, Chin/0000-0002-2819-7576 FU NIH [T32DK007191, K07CA107060] FX We would like to thank Drs. Carlos Fernandezdel Castillo of General Surgery and William R. Brugge of the GI Unit at Massachusetts General Hospital for generously providing their expertise in this study. Edward S. Huang is supported by the NIH T32DK007191. Chin Hur is supported by NIH K07CA107060. NR 59 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAR PY 2010 VL 55 IS 3 BP 852 EP 860 DI 10.1007/s10620-009-1014-y PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 556UD UT WOS:000274617500040 PM 19834805 ER PT J AU Contreras, CM Akbay, EA Gallardo, TD Haynie, JM Sharma, S Tagao, O Bardeesy, N Takahashi, M Settleman, J Wong, KK Castrillon, DH AF Contreras, Cristina M. Akbay, Esra A. Gallardo, Teresa D. Haynie, J. Marshall Sharma, Sreenath Tagao, Osamu Bardeesy, Nabeel Takahashi, Masaya Settleman, Jeff Wong, Kwok-Kin Castrillon, Diego H. TI Lkb1 inactivation is sufficient to drive endometrial cancers that are aggressive yet highly responsive to mTOR inhibitor monotherapy SO DISEASE MODELS & MECHANISMS LA English DT Article ID GENOTYPE-CORRELATED SENSITIVITY; PEUTZ-JEGHERS SYNDROME; TUMOR SUPPRESSION; MAMMALIAN TARGET; CERVICAL-CANCER; ESTROUS-CYCLE; MOUSE UTERUS; CARCINOMA; PTEN; GENE AB Endometrial cancer - the most common malignancy of the female reproductive tract - arises from the specialized epithelial cells that line the inner surface of the uterus. Although significant advances have been made in our understanding of this disease in recent years, one significant limitation has been the lack of a diverse genetic toolkit for the generation of mouse models. We identified a novel endometrial-specific gene, Sprr2f, and developed a Sprr2f-Cre transgene for conditional gene targeting within endometrial epithelium. We then used this tool to generate a completely penetrant Lkb1 (also known as Stk11)-based mouse model of invasive endometrial cancer. Strikingly, female mice with homozygous endometrial Lkb1 inactivation did not harbor discrete endometrial neoplasms, but instead underwent diffuse malignant transformation of their entire endometrium with rapid extrauterine spread and death, suggesting that Lkb1 inactivation was sufficient to promote the development of invasive endometrial cancer. Mice with heterozygous endometrial Lkb1 inactivation only rarely developed tumors, which were focal and arose with much longer latency, arguing against the idea - suggested by some prior studies - that Lkb1 is a haploinsufficient tumor suppressor. Lastly, the finding that endometrial cancer cell lines were especially sensitive to the mTOR (mammalian target of rapamycin) inhibitor rapamycin prompted us to test its efficacy against Lkb1-driven endometrial cancers. Rapamycin monotherapy not only greatly slowed disease progression, but also led to striking regression of pre-existing tumors. These studies demonstrate that Lkb1 is a uniquely potent endometrial tumor suppressor, but also suggest that the clinical responses of some types of invasive cancers to mTOR inhibitors may be linked to Lkb1 status. C1 [Contreras, Cristina M.; Akbay, Esra A.; Gallardo, Teresa D.; Haynie, J. Marshall; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Contreras, Cristina M.; Akbay, Esra A.; Gallardo, Teresa D.; Haynie, J. Marshall; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Sharma, Sreenath; Bardeesy, Nabeel; Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Sharma, Sreenath; Bardeesy, Nabeel; Settleman, Jeff] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wong, Kwok-Kin] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Castrillon, DH (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. EM diego.castrillon@utsouthwestern.edu OI wong, kwok kin/0000-0001-6323-235X FU National Cancer Institute [1R01CA13718, 1U01CA14157]; Sidney Kimmel Translational Science Awards; American Cancer Society [RSG0907901MGO]; Cancer Prevention and Research Institute of Texas [RP100550]; Simmons Comprehensive Cancer Center; NIH NRSA FX We thank Lane Shirley and Dr Preeti Kshirsagar for technical assistance, and Dr Song Zhang and Dr Chul Ahn of the Department of Clinical Sciences and the Simmons Comprehensive Cancer Center for help with statistical analysis. This work was supported by grants from the National Cancer Institute (1R01CA13718 to D.H.C. and 1U01CA14157 to D.H.C., K.-K.W. and N.B.), Sidney Kimmel Translational Science Awards (to D.H.C., K.-K.W. and N.B.), the American Cancer Society (RSG0907901MGO to D.H.C.), the Cancer Prevention and Research Institute of Texas (RP100550 to D.H.C.) and the Simmons Comprehensive Cancer Center. C.M.C. was funded through an NIH NRSA F31 fellowship. Deposited in PMC for release after 12 months. This article is freely accessible online from the date of publication. NR 45 TC 51 Z9 52 U1 2 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD MAR-APR PY 2010 VL 3 IS 3-4 BP 181 EP 193 DI 10.1242/dmm.004440 PG 13 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 590LE UT WOS:000277226800010 PM 20142330 ER PT J AU Su, LHJ Auluck, PK Outeiro, TF Yeger-Lotem, E Kritzer, JA Tardiff, DF Strathearn, KE Liu, F Cao, SS Hamamichi, S Hill, KJ Caldwell, KA Bell, GW Fraenkel, E Cooper, AA Caldwell, GA McCaffery, JM Rochet, JC Lindquist, S AF Su, Linhui Julie Auluck, Pavan K. Outeiro, Tiago Fleming Yeger-Lotem, Esti Kritzer, Joshua A. Tardiff, Daniel F. Strathearn, Katherine E. Liu, Fang Cao, Songsong Hamamichi, Shusei Hill, Kathryn J. Caldwell, Kim A. Bell, George W. Fraenkel, Ernest Cooper, Antony A. Caldwell, Guy A. McCaffery, J. Michael Rochet, Jean-Christophe Lindquist, Susan TI Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson's disease models SO DISEASE MODELS & MECHANISMS LA English DT Article ID LACKING ALPHA-SYNUCLEIN; MULTIPLE SYSTEM ATROPHY; SACCHAROMYCES-CEREVISIAE; LEWY BODIES; NEURODEGENERATIVE DISEASES; ENDOPLASMIC-RETICULUM; OXIDATIVE STRESS; TRANSGENIC MICE; YEAST-CELLS; GENE AB alpha-Synuclein (alpha-syn) is a small lipid-binding protein involved in vesicle trafficking whose function is poorly characterized. It is of great interest to human biology and medicine because alpha-syn dysfunction is associated with several neurodegenerative disorders, including Parkinson's disease (PD). We previously created a yeast model of alpha-syn pathobiology, which established vesicle trafficking as a process that is particularly sensitive to alpha-syn expression. We also uncovered a core group of proteins with diverse activities related to alpha-syn toxicity that is conserved from yeast to mammalian neurons. Here, we report that a yeast strain expressing a somewhat higher level of alpha-syn also exhibits strong defects in mitochondria! function. Unlike our previous strain, genetic suppression of endoplasmic reticulum (ER)-to-Golgi trafficking alone does not suppress alpha-syn toxicity in this strain. In an effort to identify individual compounds that could simultaneously rescue these apparently disparate pathological effects of alpha-syn, we screened a library of 115,000 compounds. We identified a class of small molecules that reduced alpha-syn toxicity at micromolar concentrations in this higher toxicity strain. These compounds reduced the formation of alpha-syn foci, re-established ER-to-Golgi trafficking and ameliorated alpha-syn-mediated damage to mitochondria. They also corrected the toxicity of alpha-syn in nematode neurons and in primary rat neuronal midbrain cultures. Remarkably, the compounds also protected neurons against rotenone-induced toxicity, which has been used to model the mitochondrial defects associated with PD in humans. That single compounds are capable of rescuing the diverse toxicities of alpha-syn in yeast and neurons suggests that they are acting on deeply rooted biological processes that connect these toxicities and have been conserved for a billion years of eukaryotic evolution. Thus, it seems possible to develop novel therapeutic strategies to simultaneously target the multiple pathological features of PD. C1 [Su, Linhui Julie; Auluck, Pavan K.; Outeiro, Tiago Fleming; Yeger-Lotem, Esti; Kritzer, Joshua A.; Tardiff, Daniel F.; Bell, George W.; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Lindquist, Susan] Howard Hughes Med Inst, Cambridge, MA 02142 USA. [Auluck, Pavan K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Auluck, Pavan K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yeger-Lotem, Esti; Fraenkel, Ernest] MIT, Dept Biol Engn, Cambridge, MA 02142 USA. [Strathearn, Katherine E.; Liu, Fang; Rochet, Jean-Christophe] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. [Cao, Songsong; Hamamichi, Shusei; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA. [Hill, Kathryn J.; Cooper, Antony A.] Garvan Inst Med Res, Diabet Program, Sydney, NSW 2010, Australia. [Hill, Kathryn J.; Cooper, Antony A.] Univ New S Wales, Sch Biotechnol & Biomol Sci, Fac Sci, Sydney, NSW 2052, Australia. [McCaffery, J. Michael] Johns Hopkins Univ, Dept Biol, Integrated Imaging Ctr, Baltimore, MD 21218 USA. RP Lindquist, S (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM lindquist_admin@wi.mit.edu RI YEGER LOTEM, ESTI/F-1540-2012; OI Fraenkel, Ernest/0000-0001-9249-8181; Yeger-Lotem, Esti/0000-0002-8279-7898 FU MGH/MIT Morris Udall Center of Excellence in Parkinson's Disease Research [NS038372]; Michael J. Fox Foundation; Howard Hughes Medical Institute; National Institutes of Health [NS049221]; American Parkinson's Disease Association; FoldRx Pharmaceuticals FX S.L. acknowledges support from the MGH/MIT Morris Udall Center of Excellence in Parkinson's Disease Research (NS038372), the Michael J. Fox Foundation and a Collaborative Initiative Award from the Howard Hughes Medical Institute. C. elegant studies in the Caldwell laboratory were supported in part by grants from the Michael J. Fox Foundation and Howard Hughes Medical Institute. Primary midbrain culture studies in the Rochet laboratory were supported by grants from the National Institutes of Health (NS049221) and the American Parkinson's Disease Association. Deposited in PMC for release after 6 months.; S.L. is a founder of, a former member of the Board of Directors of and has received consulting fees from FoldRx Pharmaceuticals, a company that investigates drugs to treat protein folding diseases. A.A.C. and S.L. are inventors of patents and patent applications that have been licensed to FoldRx. S.L. is also a member of the Board of Directors of Johnson & Johnson. A.A.C. and J.-C.R. have received consulting fees from FoldRx Pharmaceuticals, and J.-C.R., K.A.C. and G.A.C. have received payment from FoldRx for testing drugs in their laboratories. NR 69 TC 83 Z9 83 U1 6 U2 15 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD MAR-APR PY 2010 VL 3 IS 3-4 BP 194 EP 208 DI 10.1242/dmm.004267 PG 15 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 590LE UT WOS:000277226800011 PM 20038714 ER PT J AU Davis, LL Wisniewski, SR Howland, RH Trivedi, MH Husain, MM Fava, M McGrath, PJ Balasubramani, GK Warden, D Rush, AJ AF Davis, Lori L. Wisniewski, Stephen R. Howland, Robert H. Trivedi, Madhukar H. Husain, Mustafa M. Fava, Maurizio McGrath, Patrick J. Balasubramani, G. K. Warden, Diane Rush, A. John TI Does comorbid substance use disorder impair recovery from major depression with SSRI treatment? An analysis of the STAR*D level one treatment outcomes SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Major depression; Substance use disorders; Citalopram; Alcohol use disorders; Dual diagnosis; Comorbidity ID SEQUENCED TREATMENT ALTERNATIVES; ALCOHOL-USE DISORDERS; DIAGNOSTIC SCREENING QUESTIONNAIRE; REPORT QIDS-SR; PSYCHIATRIC-DISORDERS; ANTIDEPRESSANT TREATMENT; PSYCHOMETRIC EVALUATION; CLINICAL-FEATURES; SUICIDAL-BEHAVIOR; ABUSE DEPENDENCE AB Many patients with major depressive disorder (MDD) present with concurrent substance use disorders (SUDs),which has been thought to impair their response to antidepressants. Clinicians often delay antidepressant treatment until sustained sobriety has been established. Unfortunately, these comorbid subjects are typically excluded from depression treatment trials, leaving a gap in understanding the treatment outcomes. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, 2876 adult outpatients diagnosed with nonpsychotic MDD were prospectively treated with the selective serotonin-reuptake inhibitor (SSRI), citalopram, and returned for at least one post-baseline visit. Participants with SUD (29%) and without SUD (71%) were compared in regard to baseline clinical and sociodemographic features and treatment response. The group with MDD and SUD was further subdivided into those with alcohol only, drug only, and both alcohol and drug use. Despite clear sociodemographic and clinical differences, there were no significant differences between groups in the time to achieve response or rates of response to citalopram: however, those who endorsed both alcohol and drug use had significantly reduced rates of remission and significantly increased times to reach remission compared to the MDD group without SUD. In addition, subjects with MDD and SUD had higher risk of psychiatric serious adverse events (3.3% vs. 1.5%) and hospitalization (2.8% vs. 1.2%). The results indicate that first-line treatment with citalopram in depressed patients with alcohol or drug use respond as well as those without SUD. More intensive treatment is most likely needed for MDD patients with both drug and alcohol use disorders. (C) 2009 Published by Elsevier Ireland Ltd. C1 [Davis, Lori L.] VA Med Ctr, Tuscaloosa, AL 35404 USA. [Davis, Lori L.] Univ Alabama, Birmingham, AL 35294 USA. [Wisniewski, Stephen R.; Balasubramani, G. K.] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA. [Howland, Robert H.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Trivedi, Madhukar H.; Husain, Mustafa M.; Warden, Diane] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McGrath, Patrick J.] Columbia Univ, New York, NY 10032 USA. [McGrath, Patrick J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Rush, A. John] Duke Natl Univ Singapore, Singapore 169857, Singapore. RP Davis, LL (reprint author), VA Med Ctr 151, 3701 Loop Rd E, Tuscaloosa, AL 35404 USA. EM lori.davis@va.gov RI McGrath, Patrick/I-6410-2013; Howland, Robert/K-6937-2015; OI McGrath, Patrick/0000-0001-7217-7321; Howland, Robert/0000-0002-6533-6010; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU Bristol-Myers Squibb Company; Forest Pharmaceuticals Inc.; GlaxoSmithKline, King Pharmaceuticals, Organon Inc.; Pfizer Inc. FX We would like to acknowledge the administrative support of VA Research and Development at participating VA Medical Centers. We appreciate the support of Bristol-Myers Squibb Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, King Pharmaceuticals, Organon Inc., Pfizer Inc., and Wyeth-Ayerst Laboratories in providing medications at no cost for this trial. We also acknowledge the editorial support of Bill McCurdy of e.Solution@verison.net. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, of organizations imply endorsement by the U.S. Government. NR 59 TC 28 Z9 28 U1 2 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 1 PY 2010 VL 107 IS 2-3 BP 161 EP 170 DI 10.1016/j.drugalcdep.2009.10.003 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 571DX UT WOS:000275732700007 PM 19945804 ER PT J AU Garber, J AF Garber, J. TI Genetics in cancer prevention SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 6th International Conference on Clinical Cancer Prevention (SG-CAP 2010) CY MAR 18-20, 2010 CL St Gallen, SWITZERLAND SP Novartis Schweiz AG C1 [Garber, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD MAR PY 2010 VL 8 IS 2 BP 2 EP 2 DI 10.1016/S1359-6349(10)70740-0 PG 1 WC Oncology SC Oncology GA 584MH UT WOS:000276755600004 ER PT J AU Pierce, L Phillips, K Griffith, K Buys, S Gaffney, D Moran, M Haffty, B Ben-David, MKB Garber, J Merajver, S Balmana, J Meirovitz, A Domchek, S AF Pierce, L. Phillips, K. Griffith, K. Buys, S. Gaffney, D. Moran, M. Haffty, B. Ben-David, M. K. B. Garber, J. Merajver, S. Balmana, J. Meirovitz, A. Domchek, S. TI Local therapy options in BRCA1/2 carriers with operable breast cancer: the importance of adjuvant chemotherapy SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT European Breast Cancer Conference CY MAR 24-24, 2010 CL Barcelona, SPAIN C1 [Pierce, L.; Griffith, K.; Merajver, S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Phillips, K.] Peter MacCallum Canc Center, Victoria, Australia. [Buys, S.; Gaffney, D.] Univ Utah, Salt Lake City, UT USA. [Moran, M.] Yale Univ, New Haven, CT USA. [Haffty, B.] UMDNJ, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Ben-David, M. K. B.] Chaim Sheba Med Ctr, Ramat Gan, Israel. [Garber, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Balmana, J.] Hosp Gen Valle Hebron, Barcelona, Spain. [Meirovitz, A.] Hadassah Med Org, Jerusalem, Israel. [Domchek, S.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD MAR PY 2010 VL 8 IS 3 BP 55 EP 55 DI 10.1016/S1359-6349(10)70034-3 PG 1 WC Oncology SC Oncology GA 584MT UT WOS:000276756900031 ER PT J AU Kuter, I Hegg, R Singer, CF Badwe, RA Lowe, ES Emeribe, UA Anderson, E Sapunar, F Bines, J Harbeck, N AF Kuter, I. Hegg, R. Singer, C. F. Badwe, R. A. Lowe, E. S. Emeribe, U. A. Anderson, E. Sapunar, F. Bines, J. Harbeck, N. TI Impact of fulvestrant 500 mg/month versus fulvestrant 250 mg/month on bone turnover markers and endometrial thickness: findings from the NEWEST study SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT European Breast Cancer Conference CY MAR 24-24, 2010 CL Barcelona, SPAIN C1 [Kuter, I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hegg, R.] Univ Sao Paulo, Sao Paulo, Brazil. [Hegg, R.] Hosp Perola Byington, Sch Med, Sao Paulo, Brazil. [Badwe, R. A.] Tata Mem Hosp, Bombay 400012, Maharashtra, India. [Lowe, E. S.; Emeribe, U. A.] AstraZeneca, Wilmington, DE USA. [Anderson, E.; Sapunar, F.] AstraZeneca, Macclesfield, Cheshire, England. [Bines, J.] Inst Nacl Canc, Rio De Janeiro, Brazil. [Harbeck, N.] Univ Cologne, Breast Ctr, Dept Obstet & Gynecol, Cologne, Germany. [Singer, C. F.] Med Univ Vienna, Div Special Gynecol, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD MAR PY 2010 VL 8 IS 3 BP 64 EP 64 DI 10.1016/S1359-6349(10)70052-5 PG 1 WC Oncology SC Oncology GA 584MT UT WOS:000276756900049 ER PT J AU Eiermann, W Miles, D Gilewski, T Trudeau, M Xu, B Barrios, C Pendergrass, K Eggleton, SP Kashala, O Shulman, L AF Eiermann, W. Miles, D. Gilewski, T. Trudeau, M. Xu, B. Barrios, C. Pendergrass, K. Eggleton, S. P. Kashala, O. Shulman, L. TI STRIDE: phase III study of therapeutic cancer vaccine L-BLP25 with hormonal treatment as first-line therapy for women with hormone receptor-positive, inoperable, locally advanced, recurrent, or metastatic breast cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT European Breast Cancer Conference CY MAR 24-24, 2010 CL Barcelona, SPAIN C1 [Eiermann, W.] Red Cross Hosp, Womens Clin, Munich, Germany. [Miles, D.] Mt Vernon Canc Ctr, Middlesex, England. [Gilewski, T.] Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, New York, NY 10021 USA. [Trudeau, M.] Odette Canc Ctr, Toronto, ON, Canada. [Xu, B.] Canc Hosp, Chinese Acad Med Sci, Beijing, Peoples R China. [Barrios, C.] Pontificia Univ Catolica Rio Grande do Sul, Hosp Sao Lucas, Ctr Hematol & Oncol, Porto Alegre, RS, Brazil. [Pendergrass, K.] Kansas City Canc Ctr, Kansas City, KS USA. [Eggleton, S. P.] Merck KGaA, GCDU, Oncology, Darmstadt, Germany. [Shulman, L.] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RI Barrios, Carlos/G-8525-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD MAR PY 2010 VL 8 IS 3 BP 87 EP 88 DI 10.1016/S1359-6349(10)70132-4 PG 2 WC Oncology SC Oncology GA 584MT UT WOS:000276756900129 ER PT J AU Hayashida, T Takahashi, F Chiba, N Brachtel, E Jinno, H Kitagawa, Y Sgroi, D Maheswaran, S AF Hayashida, T. Takahashi, F. Chiba, N. Brachtel, E. Jinno, H. Kitagawa, Y. Sgroi, D. Maheswaran, S. TI HOXB9, a gene overexpressed in breast cancer, induces angiogenesis, invasion, and lung metastasis SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT European Breast Cancer Conference CY MAR 24-24, 2010 CL Barcelona, SPAIN C1 [Hayashida, T.; Takahashi, F.; Chiba, N.; Brachtel, E.; Sgroi, D.; Maheswaran, S.] Massachusetts Gen Hosp, Charlestown, MA 02114 USA. [Jinno, H.; Kitagawa, Y.] Keio Univ, Sch Med, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD MAR PY 2010 VL 8 IS 3 BP 124 EP 124 DI 10.1016/S1359-6349(10)70253-6 PG 1 WC Oncology SC Oncology GA 584MT UT WOS:000276756900250 ER PT J AU Lin, EY Tsigrelis, C Baddour, LM Lepidi, H Rolain, JM Patel, R Raoult, D AF Lin, Eleanor Y. Tsigrelis, Constantine Baddour, Larry M. Lepidi, Hubert Rolain, Jean-Marc Patel, Robin Raoult, Didier TI Candidatus Bartonella mayotimonensis and Endocarditis SO EMERGING INFECTIOUS DISEASES LA English DT Article ID QUINTANA; PATIENT; AGENT; VALVE; CAT AB We describe a new Bartonella species for which we propose the name Candidatus Bartonella mayotimonensis. It was isolated from native aortic valve tissue of a person with infective endocarditis. The new species was identified by using PCR amplification and sequencing of 5 genes (16S rRNA gene, ftsZ, rpoB, gltA, and internal transcribed spacer region). C1 [Lin, Eleanor Y.; Tsigrelis, Constantine; Baddour, Larry M.; Patel, Robin] Mayo Clin, Rochester, MN USA. [Lepidi, Hubert; Rolain, Jean-Marc; Raoult, Didier] Univ Aix Marseille 2, Marseille, France. RP Lin, EY (reprint author), Massachusetts Gen Hosp, Thier Bldg,Rm 1101,55 Blossom St, Boston, MA 02114 USA. EM lin.eleanor@alumni.mayo.edu NR 15 TC 18 Z9 24 U1 0 U2 6 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR PY 2010 VL 16 IS 3 BP 500 EP 503 DI 10.3201/eid1603.081673 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 566WR UT WOS:000275404700021 PM 20202430 ER PT J AU Baron, R AF Baron, Roland TI Molecular and cellular basis of bone remodeling and their implications for the treatment of bone diseases SO ENDOCRINE JOURNAL LA English DT Meeting Abstract C1 [Baron, Roland] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPAN ENDOCRINE SOC PI KYOTO PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO, 604-8111, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD MAR PY 2010 VL 57 SU 2 BP S246 EP S246 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623LV UT WOS:000279742600219 ER PT J AU Demay, MB AF Demay, Marie B. TI Actions of the vitamin D receptor in the skin SO ENDOCRINE JOURNAL LA English DT Meeting Abstract C1 [Demay, Marie B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPAN ENDOCRINE SOC PI KYOTO PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO, 604-8111, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD MAR PY 2010 VL 57 SU 2 BP S244 EP S244 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623LV UT WOS:000279742600210 ER PT J AU Jueppner, H AF Jueppner, Harald TI PTH/PTHrP receptor-mediated actions of parathyroid hormone (PTH) in kidney and bone SO ENDOCRINE JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPAN ENDOCRINE SOC PI KYOTO PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO, 604-8111, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD MAR PY 2010 VL 57 SU 2 BP S244 EP S244 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623LV UT WOS:000279742600212 ER PT J AU King, G AF King, George TI Diabetic complications- Mechanisms beyond oxidative stress SO ENDOCRINE JOURNAL LA English DT Meeting Abstract C1 [King, George] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JAPAN ENDOCRINE SOC PI KYOTO PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO, 604-8111, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD MAR PY 2010 VL 57 SU 2 BP S218 EP S218 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623LV UT WOS:000279742600101 ER PT J AU Krolewski, AS AF Krolewski, Andrzej S. TI Identification of susceptibility loci for nephropathy in diabetes SO ENDOCRINE JOURNAL LA English DT Meeting Abstract C1 [Krolewski, Andrzej S.] Joslin Diabet Ctr, Boston, MA USA. [Krolewski, Andrzej S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPAN ENDOCRINE SOC PI KYOTO PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO, 604-8111, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD MAR PY 2010 VL 57 SU 2 BP S214 EP S215 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623LV UT WOS:000279742600084 ER PT J AU Kronenberg, HM AF Kronenberg, Henry M. TI Parathyroid hormone's actions on bone SO ENDOCRINE JOURNAL LA English DT Meeting Abstract C1 [Kronenberg, Henry M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPAN ENDOCRINE SOC PI KYOTO PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO, 604-8111, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD MAR PY 2010 VL 57 SU 2 BP S193 EP S193 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623LV UT WOS:000279742600004 ER PT J AU Kulkarni, RN AF Kulkarni, Rohit N. TI Growth factor signaling in the regulation of ER stress and pancreatic beta cell mass SO ENDOCRINE JOURNAL LA English DT Meeting Abstract C1 [Kulkarni, Rohit N.] Joslin Diabet Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPAN ENDOCRINE SOC PI KYOTO PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO, 604-8111, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD MAR PY 2010 VL 57 SU 2 BP S215 EP S215 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623LV UT WOS:000279742600085 ER PT J AU Seale, P Conroe, H Kajimura, S Spiegelman, B AF Seale, Patrick Conroe, Heather Kajimura, Shingo Spiegelman, Bruce TI Transcriptional control of brown adipocyte development and differentiation SO ENDOCRINE JOURNAL LA English DT Meeting Abstract C1 [Seale, Patrick] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Conroe, Heather; Kajimura, Shingo; Spiegelman, Bruce] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPAN ENDOCRINE SOC PI KYOTO PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO, 604-8111, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD MAR PY 2010 VL 57 SU 2 BP S227 EP S227 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623LV UT WOS:000279742600139 ER PT J AU Seminara, SB AF Seminara, Stephanie B. TI The first blush of puberty: The story of kisspeptin as told through mice and men SO ENDOCRINE JOURNAL LA English DT Meeting Abstract C1 [Seminara, Stephanie B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPAN ENDOCRINE SOC PI KYOTO PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO, 604-8111, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD MAR PY 2010 VL 57 SU 2 BP S293 EP S293 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623LV UT WOS:000279742600418 ER PT J AU Sykiotis, GP Tornberg, J Hall, J Quinton, R Seminara, SB Hughes, V Van Vliet, G Van Uum, S Crowley, WF Chung, WC Tsai, PS Habuchi, H Kimata, K Pitteloud, N Bulow, HE AF Sykiotis, Gerasimos P. Tornberg, Janne Hall, Janet Quinton, Richard Seminara, Stephanie B. Hughes, Virginia Van Vliet, Guy Van Uum, Stan Crowley, William F. Chung, Wilson C. Tsai, Pei-San Habuchi, Hiroko Kimata, Koji Pitteloud, Nelly Bulow, Hannes E. TI Mutations in heparan sulfate 60-sulfotransferase 1 (HS6ST1) contribute to human GnRH deficiency SO ENDOCRINE JOURNAL LA English DT Meeting Abstract C1 [Sykiotis, Gerasimos P.; Hall, Janet; Seminara, Stephanie B.; Hughes, Virginia; Crowley, William F.; Pitteloud, Nelly] Massachusetts Gen Hosp, Dept Med, Harvard Ctr Reprod Endocrine Sci, Boston, MA 02114 USA. [Sykiotis, Gerasimos P.; Hall, Janet; Seminara, Stephanie B.; Hughes, Virginia; Crowley, William F.; Pitteloud, Nelly] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Tornberg, Janne; Bulow, Hannes E.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA. [Quinton, Richard] Newcastle Univ, Inst Human Genet, Dept Endocrinol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Van Vliet, Guy] Univ Montreal, Ctr Hosp Univ Sainte Justine, Montreal, PQ, Canada. [Van Uum, Stan] Univ Western Ontario, Dept Med, Lawson Hlth Res Inst, London, ON, Canada. [Chung, Wilson C.; Tsai, Pei-San] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. [Habuchi, Hiroko; Kimata, Koji] Aichi Med Univ, Aichi, Japan. [Bulow, Hannes E.] Albert Einstein Coll Med, Dominick P Purpura Dept Neuroscience, Bronx, NY 10467 USA. RI PITTELOUD, Nelly/K-2709-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPAN ENDOCRINE SOC PI KYOTO PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO, 604-8111, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD MAR PY 2010 VL 57 SU 2 BP S332 EP S332 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623LV UT WOS:000279742600571 ER PT J AU Tseng, YH AF Tseng, Yu-Hua TI Identification of brown fat progenitors in skeletal muscle: Impact of bone morphogenetic protein 7 SO ENDOCRINE JOURNAL LA English DT Meeting Abstract C1 [Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JAPAN ENDOCRINE SOC PI KYOTO PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO, 604-8111, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD MAR PY 2010 VL 57 SU 2 BP S227 EP S227 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623LV UT WOS:000279742600138 ER PT J AU Zhang, X Rice, K Wang, YY Chen, WD Zhong, Y Nakayama, Y Zhou, YL Klibanski, A AF Zhang, Xun Rice, Kimberley Wang, Yingying Chen, Wendy Zhong, Ying Nakayama, Yuki Zhou, Yunli Klibanski, Anne TI Maternally Expressed Gene 3 (MEG3) Noncoding Ribonucleic Acid: Isoform Structure, Expression, and Functions SO ENDOCRINOLOGY LA English DT Article ID MOUSE-CHROMOSOME 12; PITUITARY-ADENOMAS; IMPRINTING CONTROL; RNA; GTL2; PREDICTION; REGION; LOCUS; DLK1; P53 AB Maternally expressed gene 3 (MEG3) is an imprinted gene highly expressed in the human pituitary. However, MEG3 expression is lost in human gonadotroph-derived pituitary adenomas and most human tumor cell lines. Expression of MEG3 in tumor cells results in growth suppression, p53 protein increase, and activation of p53 downstream targets. The MEG3 gene encodes a noncoding RNA of approximately 1700 nucleotides. There are 12 different MEG3 gene transcripts, generated by alternative splicing. They contain the common exons 1-3 and exons 8-10, but each uses one or more exons 4-7 in a different combination in the middle. MEG3 isoform expression patterns are tissue and cell type specific. Functionally, each isoform stimulates p53-mediated transactivation and suppresses tumor cell growth. We analyzed the secondary RNA folding structure of each MEG3 isoform, using the computer program mfold. All MEG3 RNA isoforms contain three distinct secondary folding motifs M1, M2, and M3. Deletion analysis showed that motifs M2 and M3 are important for p53 activation. Furthermore, a hybrid MEG3RNA, containing a piece of artificially synthesized sequence different from the wild type but folding into a similar secondary structure, retained the functions of both p53 activation and growth suppression. These results support the hypothesis that a proper folding structure of the MEG3 RNA molecule is critical for its biological functions. This study establishes for the first time the structure-function relationship of a large noncoding RNA and provides a first look into the molecular mechanisms of the biological functions of a large noncoding RNA. (Endocrinology 151: 939-947, 2010) C1 [Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org FU National Institutes of Health [R01DK40947]; Guthart Family Foundation; Jarislowsky Foundation FX This work was supported by National Institutes of Health Grant R01DK40947, The Guthart Family Foundation, and the Jarislowsky Foundation. NR 19 TC 98 Z9 115 U1 0 U2 12 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2010 VL 151 IS 3 BP 939 EP 947 DI 10.1210/en.2009-0657 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 558AF UT WOS:000274711600014 PM 20032057 ER PT J AU Wu, Y Zhao, WD Zhao, JB Zhang, YF Qin, WP Pan, JP Bauman, WA Blitzer, RD Cardozo, C AF Wu, Yong Zhao, Weidong Zhao, Jingbo Zhang, Yuanfei Qin, Weiping Pan, Jiangping Bauman, William A. Blitzer, Robert D. Cardozo, Christopher TI REDD1 Is a Major Target of Testosterone Action in Preventing Dexamethasone-Induced Muscle Loss SO ENDOCRINOLOGY LA English DT Article ID FOXO TRANSCRIPTION FACTORS; SKELETAL-MUSCLE; PROTEIN-SYNTHESIS; MAMMALIAN TARGET; ANABOLIC-STEROIDS; RAPAMYCIN PATHWAY; UBIQUITIN LIGASES; ATROPHY INVOLVE; EXPRESSION; CELLS AB Glucocorticoids are a well-recognized and common cause of muscle atrophy that can be prevented by testosterone. However, the molecular mechanisms underlying such protection have not been described. Thus, the global effects of testosterone on dexamethasone-induced changes in gene expression were evaluated in rat gastrocnemius muscle using DNA microarrays. Gene expression was analyzed after 7-d administration of dexamethasone, dexamethasone plus testosterone, or vehicle. Dexamethasone changed expression of 876 probe sets by at least 2-fold. Among these, 474 probe sets were changed by at least 2-fold in the opposite direction in the dexamethasone plus testosterone group (genes in opposition). Major biological themes represented by genes in opposition included IGF-I signaling, myogenesis and muscle development, and cell cycle progression. Testosterone completely prevented the 22-fold increase in expression of the mammalian target of rapamycin (mTOR) inhibitor regulated in development and DNA damage responses 1 (REDD1), and attenuated dexamethasone induced increased expression of eIF4E binding protein 1, Forkhead box O1, and the p85 regulatory subunit of the IGF-I receptor but prevented decreased expression of IRS-1. Testosterone attenuated increases in REDD1 protein in skeletal muscle and L6 myoblasts and prevented dephosphorylation of p70S6kinase at them TOR-dependentsite Thr389 in L6 myoblast cells. Effects of testosterone on REDD1 mRNA levels occurred within 1h, required the androgen receptor, were blocked by bicalutamide, and were due to inhibition of transcriptional activation of REDD1 by dexamethasone. These data suggest that testosterone blocks dexamethasone-induced changes in expression of REDD1 and other genes that collectively would otherwise down-regulate mTOR activity and hence also down-regulate protein synthesis. (Endocrinology 151: 1050-1059, 2010) C1 [Wu, Yong; Zhao, Weidong; Zhao, Jingbo; Zhang, Yuanfei; Qin, Weiping; Pan, Jiangping; Bauman, William A.; Cardozo, Christopher] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Qin, Weiping; Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, Dept 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, 953 So Blvd, Bronx, NY 10468 USA. EM Chris.Cardozo@mssm.edu FU Veterans Health Administration, Rehabilitation Research and Development Service [B4162C, B3347K, B3522R]; National Institutes of Health [GM054508] FX This work was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (Grant B4162C to W.A.B., and B3347K and B3522R to C.C.). R.D.B. was supported by National Institutes of Health Grant GM054508. NR 52 TC 27 Z9 27 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2010 VL 151 IS 3 BP 1050 EP 1059 DI 10.1210/en.2009-0530 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 558AF UT WOS:000274711600025 PM 20032058 ER PT J AU Pojoga, LH Romero, JR Yao, TM Loutraris, P Ricchiuti, V Coutinho, P Guo, C Lapointe, N Stone, JR Adler, GK Williams, GH AF Pojoga, Luminita H. Romero, Jose R. Yao, Tham M. Loutraris, Paul Ricchiuti, Vincent Coutinho, Patricia Guo, Christine Lapointe, Nathalie Stone, James R. Adler, Gail K. Williams, Gordon H. TI Caveolin-1 Ablation Reduces the Adverse Cardiovascular Effects of N-omega-Nitro-L-Arginine Methyl Ester and Angiotensin II SO ENDOCRINOLOGY LA English DT Article ID RAT CARDIAC FIBROBLASTS; ESTROGEN-RECEPTOR-ALPHA; SMOOTH-MUSCLE-CELLS; KINASE-C-DELTA; TYPE-1 RECEPTOR; OXIDE SYNTHASE; KNOCKOUT MICE; NULL-MICE; ENDOTHELIAL-CELLS; PULMONARY DEFECTS AB Caveolae are the major cellular membrane structure through which extracellular mediators transmit information to intracellular signaling pathways. In vascular tissue (but not ventricular myocardium), caveolin-1 (cav-1) is the main component of caveolae; cav-1 modulates enzymes and receptors, such as the endothelial nitric oxide synthase and the angiotensin II (AngII) type 1 receptor. Evidence suggests that AngII and aldosterone (ALDO) are important mediators of ventricular injury. We have described a model of biventricular damage in rodents that relies on treatment with N-omega-nitro-L-arginine methyl ester (L-NAME ( nitric oxide synthase inhibitor)) and AngII. This damage initiated at the vascular level and was observed only in the presence of ALDO and an activated mineralocorticoid receptor (MR). We hypothesize that cav-1 modulates the adverse cardiac effects mediated by ALDO in this animal model. To test this hypothesis, we assessed the ventricular damage and measures of inflammation, in wild-type (WT) and cav-1 knockout (KO) mice randomized to either placebo or L-NAME/AngII treatment. Despite displaying cardiac hypertrophy at baseline and higher blood pressure responses to L-NAME/AngII, cav-1 KO mice displayed, as compared with WT, decreased treatment-induced biventricular damage as well as decreased transcript levels of the proinflammatory marker plasminogen activator inhibitor-1. Additionally, L-NAME/AngII induced an increase in cardiac MR levels in WT but not cav-1-ablated mice. Moreover and despite similar circulating ALDO levels in both genotypes, the myocardial damage (as determined histologically and by plasminogen activator inhibitor-1 mRNA levels) was less sensitive to ALDO levels in cav-1 KO vs. WT mice, consistent with decreased MR signaling in the cav-1 KO. Thus, we conclude that the L-NAME/AngII-induced biventricular damage is mediated by a mechanism partially dependent on cav-1 and signaling via MR/ALDO. (Endocrinology 151: 1236-1246, 2010) C1 [Pojoga, Luminita H.; Romero, Jose R.; Yao, Tham M.; Loutraris, Paul; Ricchiuti, Vincent; Coutinho, Patricia; Guo, Christine; Lapointe, Nathalie; Adler, Gail K.; Williams, Gordon H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Stone, James R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Williams, GH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM gwilliams@partners.org OI Lian, Christine/0000-0003-4626-1612 FU National Institutes of Health [5T32HL007609, IL096518, ES014462, HL63423, HL069208]; American Heart Association [0735609T] FX Address all correspondence and requests for reprints to: Gordon H. Williams, M. D., Brigham and Women's Hospital/Harvard Medical School, Department of Endocrinology, Diabetes, and Hypertension, 221 Longwood Avenue, Boston, Massachusetts 02115. E-mail: gwilliams@partners.org.; This work was supported by National Institutes of Health Grants 5T32HL007609 (to L. H. P. and C. G.), IL096518 and ES014462 ( to J.R.R.), HL63423 (to G. K. A.), and HL069208 (to G. H. W.). L. H. P. is supported by a Scientist Development Grant from the American Heart Association (0735609T).; Disclosure Summary: The authors have nothing to declare. NR 49 TC 28 Z9 28 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2010 VL 151 IS 3 BP 1236 EP 1246 DI 10.1210/en.2009-0514 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 558AF UT WOS:000274711600044 PM 20097717 ER PT J AU Kimura, F Sidis, Y Bonomi, L Xia, Y Schneyer, A AF Kimura, Fuminori Sidis, Yisrael Bonomi, Lara Xia, Yin Schneyer, Alan TI The Follistatin-288 Isoform Alone Is Sufficient for Survival But Not for Normal Fertility in Mice SO ENDOCRINOLOGY LA English DT Article ID PRIMORDIAL FOLLICLE DEVELOPMENT; STIMULATING-HORMONE; FEMALE FERTILITY; GRANULOSA-CELL; ACTIVIN; BINDING; GENE; FOLLICULOGENESIS; PROTEINS; DEFECTS AB Follistatin (FST) is a natural antagonist of activin and related TGF beta superfamily ligands that exists as three protein isoforms differing in length at the C terminus. The longest FST315 isoform is found in the circulation, whereas the shortest FST288 isoform is typically found in or on cells and tissues, and the intermediate FST303 isoform is found in gonads. We recently demonstrated that the FST isoforms have distinct biological actions in vitro that, taken together with the differential distribution, suggests they may also have different roles in vivo. To explore the specific role of individual FST isoforms, we created a single-isoform FST288-only mouse. In contrast to the neonatal death of FST global knockout mice, FST288-only mice survive to adulthood. Although they appear normal, FST288-only mice have fertility defects including reduced litter size and frequency. Follicles were counted in ovaries from 8.5- to 400-d-old females. Significantly fewer morphologically healthy antral follicles were found in 100- to 250-d FST288-only ovaries, but there were significantly more secondary, primary, and primordial follicles detected at d 8.5 in FST288-only ovaries. However, depletion of this primordial follicle pool is more rapid in FST288-only females resulting in a deficit by 250d of age and early cessation of reproduction. Superovulated FST288-only females have fewer ovulated eggs and embryos. These results indicate that the FST isoforms have different activities in vivo, that the FST288-only isoform is sufficient for development, and that loss of FST303 and FST315 isoforms results in fertility defects that resemble activin hyperactivity and premature ovarian failure. (Endocrinology 151: 1310-1319, 2010) C1 [Kimura, Fuminori; Bonomi, Lara; Schneyer, Alan] Univ Massachusetts Amherst, Dept Biol, Pioneer Valley Life Sci Inst, Springfield, MA 01199 USA. [Sidis, Yisrael] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Xia, Yin] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Schneyer, A (reprint author), Pioneer Valley Life Sci Inst, 3601 Main St,2nd Floor, Springfield, MA 01107 USA. EM alan.schneyer@bhs.org FU National Institutes of Health [R01DK075058, R21HD062859] FX This work was supported by National Institutes of Health Grants R01DK075058 and R21HD062859 (to A.L.S.). NR 28 TC 25 Z9 25 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2010 VL 151 IS 3 BP 1310 EP 1319 DI 10.1210/en.2009-1176 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 558AF UT WOS:000274711600051 PM 20032047 ER PT J AU Camelo-Piragua, S Zambrano, E Pantanowitz, L AF Camelo-Piragua, Sandra Zambrano, Eduardo Pantanowitz, Liron TI Langerhans cell histiocytosis SO ENT-EAR NOSE & THROAT JOURNAL LA English DT Article ID CHILDREN; HEAD C1 [Camelo-Piragua, Sandra] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Zambrano, Eduardo] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. [Pantanowitz, Liron] Tufts Univ, Sch Med, Baystate Med Ctr, Dept Pathol, Springfield, MA 01199 USA. RP Camelo-Piragua, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 5 TC 3 Z9 6 U1 0 U2 0 PU VENDOME GROUP LLC PI NEW YORK PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA SN 0145-5613 J9 ENT-EAR NOSE THROAT JI ENT-Ear Nose Throat J. PD MAR PY 2010 VL 89 IS 3 BP 112 EP 113 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA 573XS UT WOS:000275950300006 PM 20229474 ER PT J AU Park, BJ Kalish, RJ Vercillo, AP AF Park, Brian J. Kalish, Randy J. Vercillo, Arthur P. TI Disseminated plasmacytoma of the thyroid SO ENT-EAR NOSE & THROAT JOURNAL LA English DT Article ID EXTRAMEDULLARY PLASMACYTOMA; HEAD AB Extramedullary plasmacytomas most commonly occur in the nasal cavity, nasopharynx, paranasal sinuses, and larynx. Thyroid involvement is rare, as fewer than 75 cases have been previously reported in the literature. We report a new case of dissentinated plasmacytoma of the thyroid, which occurred in a 68-year-old woman. The diagnosis was made with an incisional biopsy. The patient initially experienced a complete response to radiotherapy (46.8 Gy in 26 fractions), but she developed multiple metastases at distant sites, including the breast, abdominal wall, and buttock despite various chemotherapy regimens. Ultimately, she was placed on palliative radiotherapy. We also briefly review the diagnostic and treatment options for patients with extramedullary plasmacytoma. C1 [Park, Brian J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Kalish, Randy J.] St Josephs Hosp, Dept Pathol, Syracuse, NY USA. [Vercillo, Arthur P.] SUNY Upstate Med Univ, Dept Otolaryngol, Syracuse, NY USA. [Vercillo, Arthur P.] SUNY Upstate Med Univ, Dept Surg, Syracuse, NY USA. RP Vercillo, AP (reprint author), 5100 W Taft Rd 2E, Liverpool, NY 13088 USA. EM apvmd@aol.com NR 7 TC 0 Z9 1 U1 0 U2 0 PU VENDOME GROUP LLC PI NEW YORK PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA SN 0145-5613 J9 ENT-EAR NOSE THROAT JI ENT-Ear Nose Throat J. PD MAR PY 2010 VL 89 IS 3 BP 137 EP 139 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 573XS UT WOS:000275950300013 PM 20229481 ER PT J AU White, A Williams, PA Hellier, JL Clark, S Dudek, FE Staley, KJ AF White, Andrew Williams, Philip A. Hellier, Jennifer L. Clark, Suzanne Dudek, F. Edward Staley, Kevin J. TI EEG spike activity precedes epilepsy after kainate-induced status epilepticus SO EPILEPSIA LA English DT Article DE Seizures; Temporal lobe; EEG; Kainic acid; Epileptogenesis ID TEMPORAL-LOBE EPILEPSY; HEAD-INJURY; POSTTRAUMATIC EPILEPSY; SYNAPTIC REORGANIZATION; NEURON DENSITIES; FASCIA-DENTATA; RISK-FACTORS; KAINIC ACID; RAT MODEL; SEIZURES AB P>Purpose: Chronic epilepsy frequently develops after brain injury, but prediction of which individual patient will develop spontaneous recurrent seizures (i.e., epilepsy) is not currently possible. Here, we use continuous radiotelemetric electroencephalography (EEG) and video monitoring along with automated computer detection of EEG spikes and seizures to test the hypothesis that EEG spikes precede and are correlated with subsequent spontaneous recurrent seizures. Methods: The presence and pattern of EEG spikes was studied during long recording epochs between the end of status epilepticus (SE) induced by three different doses of kainate and the onset of chronic epilepsy. Results: The presence of spikes, and later spike clusters, over several days after SE before the first spontaneous seizure, was consistently associated with the development of chronic epilepsy. The rate of development of epilepsy (i.e., increase in seizure frequency) was strongly correlated with the frequency of EEG spikes and the cumulative number of EEG spikes after SE. Conclusions: The temporal features of EEG spikes (i.e., their presence, frequency, and pattern [clusters]) when analyzed over prolonged periods, may be a predictive biomarker for the development of chronic epilepsy after brain injury. Future clinical trials using prolonged EEG recordings may reveal the diagnostic utility of EEG spikes as predictors of subsequent epilepsy in brain-injured humans. C1 [White, Andrew; Hellier, Jennifer L.; Staley, Kevin J.] Univ Colorado, Sch Med, Dept Pediat, Denver, CO 80262 USA. [White, Andrew; Hellier, Jennifer L.; Staley, Kevin J.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80262 USA. [Williams, Philip A.; Clark, Suzanne; Dudek, F. Edward] Colorado State Univ, Dept Biomed Sci, Ft Collins, CO 80523 USA. RP Staley, KJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 915,55 Fruit St, Boston, MA 02114 USA. EM Kstaley@partners.org FU NIH [NS045144, NS34360] FX This research was supported by NIH grants NS045144 (F.E.D.) and NS34360 (K.J.S.).We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. NR 47 TC 52 Z9 52 U1 2 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAR PY 2010 VL 51 IS 3 BP 371 EP 383 DI 10.1111/j.1528-1167.2009.02339.x PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 564CP UT WOS:000275190200006 PM 19845739 ER PT J AU Pramuka, M Hendrickson, R Van Cott, AC AF Pramuka, Michael Hendrickson, Rick Van Cott, Anne C. TI Survey results of Internet and computer usage in veterans with epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE Computer access; Self-management; Access to care; Internet; Veterans ID MANAGEMENT; PROGRAM; THERAPY AB After our study of a self-management intervention for epilepsy [1], we gathered data on Internet use and computer availability to assess the feasibility of computer-based interventions in a veteran population. Veterans were asked to complete an anonymous questionnaire that gathered information regarding seizures/epilepsy in addition to demographic data, Internet use, computer availability, and interest in distance education regarding epilepsy. Three hundred twenty-four VA neurology clinic patients completed the survey. One hundred twenty-six self-reported a medical diagnosis of epilepsy and constituted the epilepsy/seizure group. For this group of veterans, the need for remote/distance-based interventions was validated given the majority of veterans traveled long distances (>2 hours). Only 51% of the epilepsy/seizure group had access to the Internet, and less than half (42%) expressed an interest in getting information on epilepsy self-management on their computer, suggesting that Web-based interventions may not be an optimal method for a self-management intervention in this population. Published by Elsevier Inc. C1 [Pramuka, Michael; Hendrickson, Rick; Van Cott, Anne C.] Univ Pittsburgh, Pittsburgh, PA USA. [Van Cott, Anne C.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Van Cott, AC (reprint author), MDP, Div Neurol, 111N-U VAPHS,Univ Dr C, Pittsburgh, PA 15240 USA. EM Anne.VanCott@va.gov FU Centers for Disease Control and Prevention FX The authors acknowledge the financial and administrative support of the Epilepsy Program of the Centers for Disease Control and Prevention and, in particular, Ms. Rosemarie Kobau, MPH. We are grateful for the support in survey collection, data entry, and study administration provided by Ms. Vivian Brice, R.N. NR 10 TC 9 Z9 9 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD MAR PY 2010 VL 17 IS 3 BP 366 EP 368 DI 10.1016/j.yebeh.2009.11.016 PG 3 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 574YK UT WOS:000276029900010 PM 20116339 ER PT J AU Tan, AU Hoffman, B Rosas, SE AF Tan, Ainah U. Hoffman, Brenda Rosas, Sylvia E. TI PATIENT PERCEPTION OF RISK FACTORS ASSOCIATED WITH CHRONIC KIDNEY DISEASE MORBIDITY AND MORTALITY SO ETHNICITY & DISEASE LA English DT Article DE Chronic Kidney Disease; Patient Knowledge; Patient Perception; Race Differences; Survey ID UNITED-STATES; CARE; EDUCATION; CKD; POPULATION; GUIDELINES; PHYSICIANS; AWARENESS; HEALTH AB Background: Educational interventions aimed at empowering patients are successful in chronic disease management. The purpose of this study was to assess patient knowledge of risk factors and complications associated with chronic kidney disease (CKD). Methods: We determined the perception of risk factors for CKD and its complications in 229 participants with a diagnosis of CKD stage 3 and 4 who completed an anonymous questionnaire. We evaluated predictors of better knowledge as measured by total correct responses using linear regression. Results: The majority (89.1%) but not all of participants were aware of their diagnosis of CKD. Almost a third (31.5%) of patients that were aware of a diagnosis of CKD did not know their serum creatinine level compared to only 15.4% of participants with diabetes who did not know their last serum glucose level. Most participants identified hypertension (92.1%) and diabetes (86%) as risk factors for CKD, but male sex (59%) and African American race (71.6%) were selected less frequently. While glucose, proteinuria and blood pressure control were commonly associated by participants as known methods to slow progression of CKD, smoking control (79.5%) and use of renin-angiotensin system inhibitors (63.8%) were less known. After adjustment for sociodemographic factors, younger age and presence of a college degree were the only independent predictors of knowledge of CKD risk factors. Conclusions: Access to CKD education needs to be tailored to the health literacy status of each patient. Educational interventional research studies are needed in early-stage CKD to determine impact on clinical outcomes. (Ethn Dis. 2010;20:106-110) C1 Univ Penn Hlth Syst, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA USA. [Rosas, Sylvia E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Rosas, SE (reprint author), 1st Floor Founders,3400 Spruce St, Philadelphia, PA 19104 USA. EM Sylvia.rosas@uphs.upenn.edu RI Rosas, Sylvia/D-1106-2009 NR 22 TC 8 Z9 9 U1 0 U2 2 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SPR PY 2010 VL 20 IS 2 BP 106 EP 110 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 598EJ UT WOS:000277815700004 PM 20503888 ER PT J AU Yang, HY Chuzi, S Sinicropi-Yao, L Johnson, D Chen, Y Clain, A Baer, L McGrath, P Stewart, J Fava, M Papakostas, G AF Yang, Huaiyu Chuzi, Sarah Sinicropi-Yao, Lara Johnson, Dan Chen, Ying Clain, Alisabet Baer, Lee McGrath, Patrick J. Stewart, Jonathan W. Fava, Maurizio Papakostas, George I. TI Type of residual symptom and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE Depression; Unipolar; SSRI; Residual symptoms; Relapse ID STAR-ASTERISK-D; REMISSION; RECOVERY; OUTCOMES AB Relapse of major depressive disorder (MDD) is a common clinical problem. Identifying relapse predictors could lead to strategies that reduce relapse risk. This study is designed to determine whether residual symptoms predict relapse risk during the continuation/maintenance treatment of MDD. 570 MDD patients received open-label fluoxetine for 12 weeks. Under double blind conditions, 262 patients who responded by week 12 were randomly assigned to continue fluoxetine or switch to placebo for 52 weeks or until relapse. Residual symptoms were measured using the Symptom Checklist-90 and the Symptom Questionnaire. The relationship between residual symptom severity and relapse risk was assessed. Without adjusting for overall residual symptom severity, a greater severity of residual obsessive-compulsive and phobic anxiety symptoms predicted greater relapse risk. After adjusting for overall residual symptom severity, only severity of phobic anxiety symptoms predicted relapse risk. The predictive value of phobic anxiety symptoms with respect to relapse risk was independent of treatment assignment. The results indicated that there may be a specific pattern of residual symptoms associated with depressive relapse during antidepressant continuation/maintenance, which is unrelated to treatment assignment. Future studies are needed to further explore the relationship between residual symptoms and relapse risk in MDD. Clinical implications: (1) It is important to treat residual symptoms among antidepressant responders/remitters in order to decrease relapse risk. (2) Clinicians should target residual phobic anxiety symptoms in order to decrease relapse risk. (3) Clinicians should target residual obsessive-compulsive symptoms in order to decrease relapse risk. Limitations: (1) limited generalizability due to inclusion/exclusion criteria; (2) lack of active comparator treatment group; (3) post hoc analysis. C1 [Yang, Huaiyu; Chuzi, Sarah; Sinicropi-Yao, Lara; Johnson, Dan; Clain, Alisabet; Baer, Lee; Fava, Maurizio; Papakostas, George I.] Harvard Univ, Massachusetts Gen Hosp, Depress Clin & Res Program, Sch Med,Dept Psychiat, Boston, MA 02114 USA. [Chen, Ying; McGrath, Patrick J.; Stewart, Jonathan W.] Columbia Univ, Coll Phys & Surg, Depress Evaluat Serv, New York State Psychiat Inst, New York, NY USA. RP Yang, HY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Depress Clin & Res Program, Sch Med,Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM hyang7@partners.org RI McGrath, Patrick/I-6410-2013; Papakostas, George/I-6905-2013 OI McGrath, Patrick/0000-0001-7217-7321; Papakostas, George/0000-0002-2465-5103 NR 14 TC 14 Z9 15 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD MAR PY 2010 VL 260 IS 2 BP 145 EP 150 DI 10.1007/s00406-009-0031-3 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 562WF UT WOS:000275085300007 PM 19572158 ER PT J AU Papakostas, G Chuzi, S Sousa, J Fava, M AF Papakostas, George I. Chuzi, Sarah E. Sousa, Jessica L. Fava, Maurizio TI 5HT1A-mediated stimulation of cortisol release in major depression: use of non-invasive cortisol measurements to predict clinical response SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE 5-HT1A; Buspirone; Cortisol; Escitalopram; Major depressive disorder ID DEXAMETHASONE-SUPPRESSION TEST; PITUITARY-ADRENAL AXIS; ANTIDEPRESSANT TREATMENT; HORMONE RESPONSES; GROWTH-HORMONE; CORTICOTROPIN; SEROTONIN; 5-HT1A; RECEPTORS; ADOLESCENTS AB The purpose of the present study was to explore 5HT1A-mediated cortisol release in major depressive disorder (MDD) patients in order to determine whether the degree of 5HT1A-receptor sensitivity can predict response to treatment with selective serotonin reuptake inhibitors (SSRIs). We examined whether the sensitivity of the 5HT1A receptor, as measured by the difference in salivary cortisol levels immediately before and 90 min following the administration of a single dose of the 5HT1A-selective agonist buspirone, predicted treatment outcome following an 8-week, fixed-dose, open trial of the SSRI escitalopram in 17 outpatients with MDD. Change in cortisol levels before and 90 min after the administration of buspirone were not found to predict treatment outcome, whether defined as clinical response (50% or greater reduction in symptom severity), or remission of symptoms. In conclusion, in the present study, we did not find that the change in salivary cortisol levels following the administration of a 5HT1A-selective agonist predicted treatment outcome following an 8-week, fixed-dose, open-label trial of the SSRI escitalopram among outpatients with MDD. Although the 5HT1A-desensetization hypothesis is still a valid one, the results of the present study could not provide any evidence in support. C1 [Papakostas, George I.; Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Chuzi, Sarah E.; Sousa, Jessica L.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Papakostas, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Harvard Medical School/Kaplen Fellowship FX Supported by the Harvard Medical School/Kaplen Fellowship and Livingston Award in Depression Research (GIP). NR 39 TC 5 Z9 5 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD MAR PY 2010 VL 260 IS 2 BP 175 EP 180 DI 10.1007/s00406-009-0035-z PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 562WF UT WOS:000275085300010 PM 19641981 ER PT J AU Bravender, T Bryant-Waugh, R Herzog, D Katzman, D Kriepe, RD Lask, B Le Grange, D Lock, J Loeb, KL Marcus, MD Madden, S Nicholls, D O'Toole, J Pinhas, L Rome, E Sokol-Burger, M Wallin, U Zucker, N AF Bravender, T. Bryant-Waugh, R. Herzog, D. Katzman, D. Kriepe, R. D. Lask, B. Le Grange, D. Lock, J. Loeb, K. L. Marcus, M. D. Madden, S. Nicholls, D. O'Toole, J. Pinhas, L. Rome, E. Sokol-Burger, M. Wallin, U. Zucker, N. CA WCEDCA TI Classification of Eating Disturbance in Children and Adolescents: Proposed Changes for the DSM-V SO EUROPEAN EATING DISORDERS REVIEW LA English DT Article DE eating disorders; classification; children; adolescents; malnutrition ID RANDOMIZED CONTROLLED-TRIAL; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; DIAGNOSTIC-CRITERIA; BRAIN-DEVELOPMENT; FAMILY-THERAPY; DISORDERS; WEIGHT; GIRLS; BEHAVIORS AB Childhood and adolescence are critical periods of neural development and physical growth. The malnutrition and related medical complications resulting from eating disorders such as anorexia nervosa (AN), bulimia nervosa (BN) and eating disorder not otherwise specified may have more severe and potentially more protracted consequences during youth than during other age periods. The consensus opinion of an international workgroup of experts on the diagnosis and treatment of child and adolescent eating disorders is that (a) lower and more developmentally sensitive threshold's of symptom seventy (e.g lower frequency of purging behaviours, significant deviations from growth curves as indicators of clinical seventy) be used as diagnostic boundaries for children and adolescents, (b) behavioural indicators of psychological features of eating disorders be considered even in the absence of direct self-report of such symptoms and (C) multiple informants (e.g parents) be used to ascertain symptom profiles. Collectively, these recommendations will permit earlier identification and intervention to prevent the exacerbation of eating disorder symptoms. Copyright (C) 2010 John Wiley & Sons, Ltd and Eating Disorders Association C1 [Zucker, N.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. [Bravender, T.] Nationwide Childrens Hosp, Columbus, OH USA. [Bryant-Waugh, R.; Nicholls, D.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Herzog, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Katzman, D.; Pinhas, L.] Hosp Sick Children, Toronto, ON, Canada. [Katzman, D.; Pinhas, L.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Kriepe, R. D.] Western New York Comprehens Care Ctr Eating Disor, New York, NY USA. [Lask, B.] Univ London St Georges Hosp, Huntercombe Hosp, London, England. [Lask, B.] Reg Eating Disorders Serv, Oslo, Norway. [Le Grange, D.] Stanford Univ, Pal Alto, CA USA. [Lock, J.] Univ Chicago, Chicago, IL 60637 USA. [Loeb, K. L.] Mt Sinai Sch Med, New York, NY USA. [Loeb, K. L.] Fairleigh Dickinson Univ, Teaneck, NJ USA. [Marcus, M. D.] Childrens Hosp, Westmead, NSW, Australia. [Madden, S.] Western Psychiat Inst & Clin, Pittsburgh, PA USA. [O'Toole, J.] Kartini Clin Childhood Eating Disorders, Portland, OR USA. [Rome, E.] Cleveland Clin, Childrens Hosp, Cincinnati, OH USA. [Sokol-Burger, M.] Creighton Univ, Omaha, NE 68178 USA. [Wallin, U.] Univ Lund Hosp, S-22185 Lund, Sweden. RP Zucker, N (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, POB 3842, Durham, NC 27705 USA. RI Le Grange, Daniel/A-2649-2011 FU NIMH NIH HHS [K23 MH070418] NR 66 TC 49 Z9 51 U1 1 U2 58 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1072-4133 J9 EUR EAT DISORD REV JI Eur. Eat. Disord. Rev. PD MAR-APR PY 2010 VL 18 IS 2 BP 79 EP 89 DI 10.1002/erv.994 PG 11 WC Psychology, Clinical SC Psychology GA 562ZX UT WOS:000275096000004 PM 20151366 ER PT J AU Peplowska, K Becker, J Pellman, D Storchova, Z AF Peplowska, K. Becker, J. Pellman, D. Storchova, Z. TI The function of Bub1 and Sgo1 in chromosome biorientation SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the German-Society-for-Cell-Biology/German Melanoma Research Network CY MAR 10-13, 2010 CL Univ Regensburg, Regensburg, GERMANY SP German Soc Cell Biol HO Univ Regensburg C1 [Peplowska, K.; Storchova, Z.] Max Planck Inst Biochem, D-82152 Martinsried, Germany. [Becker, J.; Pellman, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM storchov@biochem.mpg.de NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD MAR PY 2010 VL 89 SU 60 BP 60 EP 60 PG 1 WC Cell Biology SC Cell Biology GA 576QY UT WOS:000276163000171 ER PT J AU Cyganek, K Hebda-Szydlo, A Katra, B Skupien, J Klupa, T Janas, I Kaim, I Sieradzki, J Reron, A Malecki, MT AF Cyganek, K. Hebda-Szydlo, A. Katra, B. Skupien, J. Klupa, T. Janas, I. Kaim, I. Sieradzki, J. Reron, A. Malecki, M. T. TI Pregnancy planning improves glycemic control and pregnancy outcomes in type 1 diabetes women on CSII and MDI SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 [Cyganek, K.; Hebda-Szydlo, A.; Katra, B.; Klupa, T.; Janas, I.; Sieradzki, J.; Malecki, M. T.] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. [Cyganek, K.; Hebda-Szydlo, A.; Katra, B.; Klupa, T.; Kaim, I.; Sieradzki, J.; Reron, A.; Malecki, M. T.] Univ Hosp, Krakow, Poland. [Kaim, I.; Reron, A.] Jagiellonian Univ, Coll Med, Dept Obstet & Perinatol, Krakow, Poland. [Skupien, J.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD MAR PY 2010 VL 40 SU 1 BP 8 EP 8 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 552BF UT WOS:000274260200023 ER PT J AU Bonnen, PE Lowe, JK Altshuler, DM Breslow, JL Stoffel, M Friedman, JM Pe'er, I AF Bonnen, Penelope E. Lowe, Jennifer K. Altshuler, David M. Breslow, Jan L. Stoffel, Markus Friedman, Jeffrey M. Pe'er, Itsik TI European admixture on the Micronesian island of Kosrae: lessons from complete genetic information SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE admixture; haplotype; population genetics; mitochondria; Y chromosome; Oceania ID POPULATION-STRUCTURE; MTDNA; ASSOCIATION; ORIGINS; GENOME; RECOMBINATION; POLYMORPHISMS; POLYNESIANS; HAPLOTYPES; ANCESTRY AB The architecture of natural variation present in a contemporary population is a result of multiple population genetic forces, including population bottleneck and expansion, selection, drift, and admixture. We seek to untangle the contribution of admixture to genetic diversity on the Micronesian island of Kosrae. Toward this goal, we used a complete genetic approach by combining a dense genome-wide map of 100 000 single-nucleotide polymorphisms (SNPs) with data from uniparental markers from the mitochondrial genome and the nonrecombining portion of the Y chromosome. These markers were typed in similar to 3200 individuals from Kosrae, representing 80% of the adult population of the island. We developed novel software that uses SNP data to delineate ancestry for individual segments of the genome. Through this analysis, we determined that 39% of Kosraens have some European ancestry. However, the vast majority of admixed individuals (77%) have European alleles spanning less than 10% of their genomes. Data from uniparental markers show most of this admixture to be male, introduced in the late nineteenth century. Furthermore, pedigree analysis shows that the majority of European admixture on Kosrae is because of the contribution of one individual. This approach shows the benefit of combining information from autosomal and uniparental polymorphisms and provides new methodology for determining ancestry in a population. European Journal of Human Genetics (2010) 18, 309-316; doi: 10.1038/ejhg.2009.180; published online 21 October 2009 C1 [Bonnen, Penelope E.] Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Lowe, Jennifer K.; Breslow, Jan L.; Stoffel, Markus; Friedman, Jeffrey M.] Rockefeller Univ, Program Mol & Human Genet, New York, NY 10021 USA. [Lowe, Jennifer K.; Altshuler, David M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lowe, Jennifer K.; Altshuler, David M.] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Lowe, Jennifer K.; Altshuler, David M.] MIT, Cambridge, MA 02139 USA. [Altshuler, David M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Friedman, Jeffrey M.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Altshuler, David M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Pe'er, Itsik] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA. RP Bonnen, PE (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, 1 Baylor Plaza,MS BCM 226, Houston, TX 77030 USA. EM pbonnen@bcm.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NIH [5 U54 CA121852] FX We acknowledge the invaluable contribution of Vita Skilling, Secretary of the Department of Health and Social Affairs for the Federated States of Micronesia, and thank her for her long-standing collaboration, without whichthis project would not be possible. We acknowledge Hiroshi Ismael who supported our studies in his capacity as a public servant and by dedicating himself to the health of the people of his homeland. We are deeply grateful to the people of Kosrae and to the Kosrae Department of Health Services for making this study possible. We thank Maude Blundell and Jackie Salit for their diligent work in creating and curating the pedigree. IP was partially supported by NIH 5 U54 CA121852. NR 30 TC 7 Z9 7 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAR PY 2010 VL 18 IS 3 BP 309 EP 316 DI 10.1038/ejhg.2009.180 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 556OY UT WOS:000274601800008 PM 19844264 ER PT J AU Kang, YJ Wang, XS Lin, SJ Hsu, YM Chang, HC AF Kang, Yoon-Joong Wang, Xiaosong Lin, Sue-Jane Hsu, Yen-Ming Chang, Hsiu-Ching TI An active CD8 alpha/pMHCI interaction is required for CD8 single positive thymocyte differentiation SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD8/pMHCI interaction; Coreceptor functions; T-cell differentiation; Viral infection; Tg mice ID MHC CLASS-I; CYTOTOXIC T-LYMPHOCYTES; CORECEPTOR FUNCTION; CRYSTAL-STRUCTURE; ALPHA-BETA; INTERMEDIATE STEPS; STRUCTURAL BASIS; VIRAL-INFECTION; CELL-RECEPTOR; EXPRESSION AB Recognition of viral antigenic peptides bound to major histocompatibility complex class I molecules (MHCI) by TCR is critical for initiating the responses of CD8(+) T cells that ultimately lead to elimination of virus-infected cells. This antigen recognition is enhanced by the CD8 coreceptor through its interaction with the peptide-MHCI complexes (pMHCI). Mouse CD8 alpha beta can form two different complexes with pMHCI via either the CD8 alpha- or CD8 beta-dominated interaction. To understand the functional significance of these complexes in vivo, we generated Tg mice carrying a variant CD8 alpha beta (CD8 alpha(m3)beta) capable of forming only the CD8 beta-dominated CD8 alpha beta/pMHCI complex. These mice show sub-optimal thymic differentiation with reduced populations of CD8(+) single-positive thymocytes. Tg CD8(+) T cells exhibit a compromised developmental capacity when competing with CD8(+) T cells from B6 mice in mixed bone marrow chimera experiments. However, once these CD8(+) T cells have emigrated to the peripheral lymphoid organs, they exhibit normal effector function against viral infection. Our observations indicate that, in addition to the CD8 activity conferred by CD8 beta-dominated CD8 alpha beta/pMHCI complexes, full thymocyte differentiation requires additional coreceptor activities conferred by CD8 alpha alpha and/or CD8 alpha beta with CD8 alpha-dominated CD8/pMHCI complexes. C1 [Chang, Hsiu-Ching] AB Biosci Inc, Allston, MA 02134 USA. [Lin, Sue-Jane; Chang, Hsiu-Ching] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. [Kang, Yoon-Joong; Wang, Xiaosong; Chang, Hsiu-Ching] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kang, Yoon-Joong; Wang, Xiaosong; Chang, Hsiu-Ching] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Hsu, Yen-Ming] Biogen Idec Inc, Drug Discovery Dept, Cambridge, MA USA. RP Chang, HC (reprint author), AB Biosci Inc, 214 Lincoln St,Suite 101, Allston, MA 02134 USA. EM hsiu-ching_chang@abbiosciences.com FU NIH [AI45789, AR35506, U01 AI073871] FX We thank Drs. Raymond M. Welsh and Ellis L. Reinherz for supporting this study. We thank Dr. Celia Schiffer for editing this manuscript, Drs. Michael Brehm and Keith Daniels for providing the Kb tetramers and Drs. Lisa Selin, Lawrence Stern and Joonsoo Kang for critical reading of the manuscript. This work was supported by NIH grant AI45789 to HCC and AR35506 and U01 AI073871 to Dr. Raymond Welsh, UMMS, respectively. NR 48 TC 0 Z9 0 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 2010 VL 40 IS 3 BP 836 EP 848 DI 10.1002/eji.200939663 PG 13 WC Immunology SC Immunology GA 573SQ UT WOS:000275935600037 PM 19950178 ER PT J AU Bonnin, M Yildiz, A Baldessarini, RJ Vieta, E AF Bonnin, M. Yildiz, A. Baldessarini, R. J. Vieta, E. TI Placebo response in trials for acute mania: a double-edged sword SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT ECNP Workshop on Neuropsychopharmacology for Young Scientists in Europe CY MAR 04-07, 2010 CL Nice, FRANCE C1 [Bonnin, M.; Vieta, E.] Clin Inst Neurosci, Bipolar disorder programme, Barcelona, Spain. [Yildiz, A.; Baldessarini, R. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, McLean Div, Boston, MA USA. RI Vieta, Eduard/I-6330-2013 OI Vieta, Eduard/0000-0002-0548-0053 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAR PY 2010 VL 20 SU 1 BP S63 EP S63 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 583IY UT WOS:000276669200073 ER PT J AU Toepker, M Schlett, CL Irlbeck, T Mahabadi, AA Bamberg, F Leidecker, C Donnelly, P Hoffmann, U AF Toepker, Michael Schlett, Christopher L. Irlbeck, Thomas Mahabadi, Amir A. Bamberg, Fabian Leidecker, Christiane Donnelly, Patrick Hoffmann, Udo TI Accuracy of dual-source computed tomography in quantitative assessment of low density coronary stenosis-a motion phantom study SO EUROPEAN RADIOLOGY LA English DT Article DE Dual-source computed tomography; Stenosis quantification; Coronary vessel phantom; Non-calcified plaque; Simulated motion ID ELECTRON-BEAM CT; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUE; PERFORMANCE EVALUATION; DIAGNOSTIC-ACCURACY; INITIAL-EXPERIENCE; MULTIDETECTOR CT; ARTERY STENTS; ANGIOGRAPHY; QUANTIFICATION AB We assessed the accuracy and reproducibility of non-calcified plaque quantification as simulated by a low-density stenosis in vessel phantoms using diameter and area measures, as well as the influence of vessel size and motion on quantification accuracy in dual-source computed tomography (DSCT). Four phantoms (2, 2.5, 3, and 4 mm in luminal diameter) made from a radiopaque Lucite (126 +/- 23 Hounsfield units, HU) simulating a fixed radiolucent concentric coronary stenosis (7 +/- 2 HU, 50% luminal narrowing) were connected to a cardiac motion simulator. Stenosis quantification was based on area and diameter measurements. All measurements were highly reproducible (all ICC a parts per thousand yen0.95, p < 0.001). The mean measured degree of stenosis was 38.0 +/- 11.7% for a single diameter measurement, resulting in a mean relative error of 22.0 +/- 18.7%, decreasing with increasing phantom size (31.9 +/- 22.1%; 25.2 +/- 20.9%; 16.3 +/- 12.8%; 14.5 +/- 11.4%; for 2-, 2.5-, 3-, and 4-mm phantoms, respectively; p < 0.0001). Measurement accuracy significantly increased to 13.3 +/- 13.9% by using area measurement (p < 0.0001). The degree of stenosis was not significantly different when comparing a motioned image with an image at rest. DSCT enables highly reproducible quantification of low density stenosis, but underestimates the degree of stenosis, especially in small vessels. Area-based measurements reflect the true degree of stenosis with higher accuracy than diameter. C1 [Toepker, Michael; Schlett, Christopher L.; Irlbeck, Thomas; Mahabadi, Amir A.; Bamberg, Fabian; Donnelly, Patrick; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Bamberg, Fabian; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Leidecker, Christiane] Siemens AG, Siemens Med Solut, Malvern, PA USA. [Toepker, Michael] Med Univ Vienna, Vienna Gen Hosp, Dept Radiol, A-1090 Vienna, Austria. [Bamberg, Fabian] Univ Munich, Univ Hosp Munich, Dept Clin Radiol, D-81377 Munich, Germany. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org FU Siemens Medical Solutions; Foundation of German Business FX This work was supported in parts by Siemens Medical Solutions. Dr. Toepker received support from the Erwin Schroedinger Fellowship Abroad, Austria. Mr. Schlett and Mr. Irlbeck were supported by a grant from the Foundation of German Business. NR 28 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD MAR PY 2010 VL 20 IS 3 BP 542 EP 548 DI 10.1007/s00330-009-1587-z PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 555VQ UT WOS:000274544800004 PM 19727745 ER PT J AU Sinclair, SJ Blais, MA Gansler, DA Sandberg, E Bistis, K LoCicero, A AF Sinclair, Samuel J. Blais, Mark A. Gansler, David A. Sandberg, Elisabeth Bistis, Kimberly LoCicero, Alice TI Psychometric Properties of the Rosenberg Self-Esteem Scale: Overall and Across Demographic Groups Living Within the United States SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article DE Rosenberg Self-Esteem Scale; self-esteem; psychometric; scaling assumptions ID ANXIETY STRESS SCALES; DEPRESSION; ADULTS; TESTS; WOMEN AB The purpose of this study was twofold: ( a) to evaluate the scaling assumptions and component structure of and present normative data for the Rosenberg Self-Esteem Scale (RSES) using a sample of US adults (N = 503), both overall and across demographic subgroups and (b) to provide new data regarding the relationship between the two RSES subcomponents of self-competence (SC) and self-liking (SL), and other demographic and clinical variables. As hypothesized, all psychometric tests supported the underlying structure of the RSES. Overall RSES scores varied significantly across age, racial and ethnic, education, employment status, income, and marital status groups. Furthermore, differences between SC and SL were also found across groups differing in gender, age, employment status, and marital status groups. The implications and limitations of this study are discussed, with an emphasis on clinical relevance. C1 [Sinclair, Samuel J.; Blais, Mark A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sinclair, Samuel J.; Blais, Mark A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gansler, David A.; Sandberg, Elisabeth] Suffolk Univ, Boston, MA USA. [LoCicero, Alice] Endicott Coll, Beverly, MA USA. RP Sinclair, SJ (reprint author), Massachusetts Gen Hosp, 1 Bowdoin,Sq 7th Floor, Boston, MA 02114 USA. EM JSincl@Post.Harvard.Edu NR 31 TC 87 Z9 89 U1 14 U2 35 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0163-2787 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD MAR PY 2010 VL 33 IS 1 BP 56 EP 80 DI 10.1177/0163278709356187 PG 25 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 555ZS UT WOS:000274556300005 PM 20164106 ER PT J AU Short, EB Kose, S Mu, QW Borckardt, J Newberg, A George, MS Kozel, FA AF Short, E. Baron Kose, Samet Mu, Qiwen Borckardt, Jeffery Newberg, Andrew George, Mark S. Kozel, F. Andrew TI Regional Brain Activation During Meditation Shows Time and Practice Effects: An Exploratory FMRI Study SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article DE anterior cingulate cortex; attention; dorsal lateral prefrontal cortex; functional MRI; meditation; time courses ID ANTERIOR CINGULATE CORTEX; WORKING-MEMORY; SLEEP-DEPRIVATION; PREFRONTAL CORTEX; TIBETAN-BUDDHIST; ATTENTION; SELECTION AB Meditation involves attentional regulation and may lead to increased activity in brain regions associated with attention such as dorsal lateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Using functional magnetic resonance imaging, we examined whether DLPFC and ACC were activated during meditation. Subjects who meditate were recruited and scanned on a 3.0 Tesla scanner. Subjects meditated for four sessions of 12 min and performed four sessions of a 6 min control task. Individual and group t-maps were generated of overall meditation response versus control response and late meditation response versus early meditation response for each subject and time courses were plotted. For the overall group (n 13), and using an overall brain analysis, there were no statistically significant regional activations of interest using conservative thresholds. A region of interest analysis of the entire group time courses of DLPFC and ACC were statistically more active throughout meditation in comparison to the control task. Moreover, dividing the cohort into short (n 8) and long-term (n 5) practitioners (10 years) revealed that the time courses of long-term practitioners had significantly more consistent and sustained activation in the DLPFC and the ACC during meditation versus control in comparison to short-term practitioners. The regional brain activations in the more practised subjects may correlate with better sustained attention and attentional error monitoring. In summary, brain regions associated with attention vary over the time of a meditation session and may differ between long- and short-term meditation practitioners. C1 [Short, E. Baron] Med Univ S Carolina, Brain Stimulat Lab, Inst Psychiat, Charleston, SC 29425 USA. [Short, E. Baron; Kose, Samet; George, Mark S.; Kozel, F. Andrew] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Newberg, Andrew] Univ Penn, Med Ctr, Div Nucl Med, Philadelphia, PA 19104 USA. [George, Mark S.; Kozel, F. Andrew] Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. [Kozel, F. Andrew] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Short, EB (reprint author), Med Univ S Carolina, Brain Stimulat Lab, Inst Psychiat, 67 President St,3North, Charleston, SC 29425 USA. EM shorteb@musc.edu RI Kozel, Frank/I-5366-2012; OI Newberg, Andrew/0000-0001-8230-1752 FU Center for Advanced Imaging Research (CAIR); University Research Committee at MUSC FX Grant support was received from a grant in kind from the Center for Advanced Imaging Research (CAIR) and the University Research Committee at MUSC. Subject participation support was received from the Charleston Tibetan Society and the Charleston Zen Center. NR 27 TC 33 Z9 33 U1 7 U2 20 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-427X J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PD MAR PY 2010 VL 7 IS 1 BP 121 EP 127 DI 10.1093/ecam/nem163 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 553DE UT WOS:000274344700016 ER PT J AU Kishi, N Macklis, JD AF Kishi, Noriyuki Macklis, Jeffrey D. TI MeCP2 functions largely cell-autonomously, but also non-cell-autonomously, in neuronal maturation and dendritic arborization of cortical pyramidal neurons SO EXPERIMENTAL NEUROLOGY LA English DT Article DE MeCP2; Rett syndrome; Mecp2-null mice; Neuronal maturation; Physical chimeras; Dendritic complexity; Callosal projection neurons ID CORTICOSPINAL MOTOR-NEURONS; CPG-BINDING PROTEIN-2; RETT-SYNDROME; CEREBRAL-CORTEX; DNA METHYLATION; MOUSE MODEL; DELAYED MATURATION; BDNF TRANSCRIPTION; IN-VIVO; MICE AB Rett syndrome is a human neurodevelopmental disorder presenting almost exclusively in female infants; it is the second most common cause of mental retardation in girls, after Down's syndrome. The identification in 1999 that mutation of the methyl-CpG-binding protein 2 (MECP2) gene on the X chromosome causes Rett syndrome has led to a rapid increase in understanding of the neurobiological basis of the disorder. However, much about the functional role of MeCP2, and the cellular phenotype of both patients with Rett syndrome and mutant Mecp2 mouse models, remains unclear. Building on prior work in which we demonstrated that cortical layer 2/3 pyramidal neurons (primarily interhemispheric "callosal projection neurons" (CPN)) have reduced dendritic complexity and smaller somata in Mecp2-null mice, here we investigate whether Mecp2 loss-of-function affects neuronal maturation cell-autonomously and/or non-cell-autonomously by creating physical chimeras. We transplanted Mecp2-null or wild-type (wt) E17-18 cortical neuroblasts and immature neurons from mice constitutively expressing enhanced green fluorescent protein (eGFP) into wt P2-3 mouse cortices to generate chimeric cortices. Mecp2-null layer 2/3 pyramidal neurons in both Mecp2-null and wt neonatal cortices exhibit equivalent reduction in dendritic complexity, and are smaller than transplanted wt neurons, independent of recipient environment. These results indicate that the phenotype of Mecp2-null pyramidal neurons results largely from cell-autonomous mechanisms, with additional non-cell-autonomous effects. Dysregulation of MeCP2 target genes in individual neuronal populations such as CPN is likely centrally involved in Rett syndrome pathogenesis. Our results indicating MeCP2 function in the centrally affected projection neuron population of CPN themselves provide a foundation and motivation for identification of transcriptionally regulated MeCP2 target genes in developing CPN. (C) 2009 Elsevier Inc. All rights reserved. C1 [Macklis, Jeffrey D.] Harvard Univ, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Neurol, Sch Med, Boston, MA 02114 USA. Harvard Univ, Program Neurosci, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Boston, MA 02114 USA. Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Macklis, JD (reprint author), Harvard Univ, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg, Sch Med, Edwards 410,50 Blossom St, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu RI Kishi, Noriyuki/L-1379-2013 FU Rett Syndrome Research Foundation/International Rett Syndrome Foundation; Japan Society for the Promotion of Science; Uehara Memorial Foundation; Sumitomo Life Social Welfare Services Foundation; NINDS [NS41590, NS45523, NS49553]; Jane and Lee Seidman Fund for CNS Research; Emily and Robert Pearlstein Fund for Nervous System Repair FX We thank Dr. Bartley Mitchell for his critical advice on cellular transplantation, and his helpful comments on this study. We thank Eiman Azim, Mollie Woodworth and Drs. Tina Lai and Jessica MacDonald for critical reading of the manuscript. We also thank Kyle MacQuarrie, Alexander Eswar, Kathryn Quinn, Karen Billmers, and Ashley Palmer for excellent technical assistance. We thank Dr. Rudolf Jaenisch for generously sharing the Mecp2 mutant mice generated in his laboratory. This work was partially supported by fellowships from the Rett Syndrome Research Foundation/International Rett Syndrome Foundation, the Japan Society for the Promotion of Science, the Uehara Memorial Foundation, and the Sumitomo Life Social Welfare Services Foundation to N.K., by grants from the Rett Syndrome Research Foundation and International Rett Syndrome Foundation to JDM, by infrastructure supported by NINDS grants NS41590, NS45523, and NS49553 to JDM, and by the Jane and Lee Seidman Fund for CNS Research, and the Emily and Robert Pearlstein Fund for Nervous System Repair. NR 57 TC 39 Z9 40 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAR PY 2010 VL 222 IS 1 BP 51 EP 58 DI 10.1016/j.expneurol.2009.12.007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 565PO UT WOS:000275306600008 PM 20025874 ER EF