FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hawes, C Kimbell, A AF Hawes, C. Kimbell, A. TI ELDER ABUSE IN ASSISTED LIVING AND RESIDENTIAL CARE: EXAMINING THE PERFORMANCE OF LICENSURE AGENCIES, LTC OMBUDSMEN AND APS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hawes, C.] Texas A&M Hlth Sci Ctr, Sch Rural Publ Hlth, College Stn, TX USA. [Kimbell, A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 153 EP 153 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810600529 ER PT J AU Echt, K Backscheider-Burridge, A Jung, J Rougeux, A Hawley, K Whitbourne, S Spiro, A AF Echt, K. Backscheider-Burridge, A. Jung, J. Rougeux, A. Hawley, K. Whitbourne, S. Spiro, A., III TI LONGITUDINAL CHANGE IN VISUAL ACUITY AND EFFECTS ON COGNITION: THE VA NORMATIVE AGING STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Echt, K.] Emory Univ, Sch Med, Atlanta VA Rehabil R&D Ctr, Atlanta, GA USA. [Backscheider-Burridge, A.] Univ Houston, Houston, TX USA. [Hawley, K.] Emory Univ, Sch Med, Atlanta VA Rehabil R&D Ctr, Decatur, GA 30033 USA. [Whitbourne, S.; Spiro, A., III] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA USA. RI Backscheider Burridge, Andrea/D-9332-2015 OI Backscheider Burridge, Andrea/0000-0001-7502-0047 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 224 EP 224 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810600779 ER PT J AU Williams, BR Woodby, L Bailey, A Ritchie, C Durham, R Burgio, K AF Williams, B. R. Woodby, L. Bailey, A. Ritchie, C. Durham, R. Burgio, K. TI PALLIATIVE CARE AT THE VA:ADAPTING TO THE CHANGING FACE OF AGING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Williams, B. R.; Woodby, L.; Bailey, A.; Ritchie, C.; Burgio, K.] Birmingham Atlanta GRECC BVAMC, Birmingham, AL USA. [Williams, B. R.; Woodby, L.; Bailey, A.; Ritchie, C.; Burgio, K.] UAB Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Durham, R.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 258 EP 258 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810600904 ER PT J AU Bolkan, C Coehlo, D Hooker, K AF Bolkan, C. Coehlo, D. Hooker, K. TI MARITAL STATUS, HEALTH GOALS, AND SOCIAL NETWORKS OF OLDER WOMEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bolkan, C.] Univ Washington, Seattle, WA USA. [Bolkan, C.] VA Puget Sound, Seattle, WA USA. [Coehlo, D.] Oregon State Univ Cascades, Bend, OR USA. [Hooker, K.] Oregon State Univ, Corvallis, OR 97331 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 346 EP 346 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810601255 ER PT J AU Spiro, A Whitbourne, S Mroczek, D AF Spiro, A. Whitbourne, S. Mroczek, D. TI IS PERSONALITY CHANGE AS REAL AS IT'S PERCEIVED? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Whitbourne, S.] VA Boston Healthcare Syst, Boston, MA USA. [Whitbourne, S.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Mroczek, D.] Purdue Univ, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 353 EP 353 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810601279 ER PT J AU Davison, E Rowe, E AF Davison, E. Rowe, E. TI OLDER WOMEN, PAST SEXUAL TRAUMA, AND CURRENT FUNCTIONING: RISKS AND RESILIENCIES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Davison, E.] Natl Ctr PTSD, Boston, MA USA. [Davison, E.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Rowe, E.] Northeastern Univ, Inst Urban Hlth Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 397 EP 397 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810601422 ER PT J AU Kvale, E Ekundayo, O Ritchie, C Ahmed, A AF Kvale, E. Ekundayo, O. Ritchie, C. Ahmed, A. TI PREDICTORS OF MORTALITY AMONG COMMUNITY-DWELLING OLDER ADULTS WITH A HISTORY OF CANCER IN A PROSPECTIVE POPULATION-BASED STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kvale, E.; Ekundayo, O.; Ritchie, C.; Ahmed, A.] Univ Alabama, Birmingham, AL USA. [Kvale, E.; Ritchie, C.; Ahmed, A.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 414 EP 414 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810601484 ER PT J AU Neupert, S Mroczek, D Spiro, A AF Neupert, S. Mroczek, D. Spiro, A., III TI WITHIN-PERSON COUPLING OF INTERPERSONAL STRESSORS AND MEDICATION ADHERENCE AMONG OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Neupert, S.] N Carolina State Univ, Dept Psychol, Raleigh, NC 27695 USA. [Mroczek, D.] Purdue Univ, W Lafayette, IN 47907 USA. [Spiro, A., III] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 438 EP 438 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810601570 ER PT J AU Phillips, LL Skinner-Falco, J Paukert, A Balsis, S Cully, J AF Phillips, L. L. Skinner-Falco, J. Paukert, A. Balsis, S. Cully, J. TI EFFECTS OF A BRIEF SKILLS-BASED INTERVENTION ON QUALITY OF LIFE AND NEGATIVE AFFECT AMONG OLDER CHRONICALLY ILL VETERANS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Phillips, L. L.; Skinner-Falco, J.; Balsis, S.; Cully, J.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Paukert, A.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 519 EP 519 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602060 ER PT J AU Brown, CJ Ekundayo, O Ritchie, C Sims, R Ahmed, A AF Brown, C. J. Ekundayo, O. Ritchie, C. Sims, R. Ahmed, A. TI HISTORY OF FREQUENT FALLS AND MORTALITY IN COMMUNITY-DWELLING OLDER ADULTS: A PROPENSITY-MATCHED PROSPECTIVE POPULATION-BASED STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Brown, C. J.; Ekundayo, O.; Ritchie, C.; Ahmed, A.] Univ Alabama, Birmingham, AL USA. [Sims, R.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 536 EP 536 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602121 ER PT J AU Keyes, C Fry, P Ong, A Sawyer, P Allman, R Martin, P MacDonald, M Margrett, J Poon, L AF Keyes, C. Fry, P. Ong, A. Sawyer, P. Allman, R. Martin, P. MacDonald, M. Margrett, J. Poon, L. TI PSYCHOSOCIAL FRONTIERS OF RESILIENCE IN LATER LIFE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Keyes, C.] Emory Univ, Atlanta, GA 30322 USA. [Fry, P.] Trinity Western Univ, Langley, BC, Canada. [Ong, A.] Cornell Univ, Ithaca, NY USA. [Sawyer, P.] UAB, Sch Med, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Allman, R.] Univ Alabama, Div Gerontol & Geriatr Med, Birmingham, AL USA. [Allman, R.] Birmingham VAMC, Birmingham, AL USA. [Martin, P.; MacDonald, M.; Margrett, J.] Iowa State Univ, Ames, IA USA. [Poon, L.] Univ Georgia, Inst Gerontol, Athens, GA 30602 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 566 EP 566 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602229 ER PT J AU Nelson, MM Smith, MA Martinson, BC Kind, A Luepker, RV AF Nelson, Melissa M. Smith, Maureen A. Martinson, Brian C. Kind, Amy Luepker, Russell V. TI Declining Patient Functioning and Caregiver Burden/Health: The Minnesota Stroke Survey-Quality of Life After Stroke Study SO GERONTOLOGIST LA English DT Article DE Burden; Competence; Functional decline; Proxies; Social exchange ID CANADIAN NEUROLOGICAL SCALE; SOCIAL-EXCHANGE; MEDICAL RECORD; OLDER-ADULTS; OF-LIFE; BURDEN; HEALTH; COMORBIDITY; DISABILITY; IMPACT AB Purpose: Caregivers of stroke patients may adapt to changes in patient functioning over time. If adaptation occurs, then caregiver burden and health may be influenced more by worsening in patient functioning than by static levels of functioning. This study examines the relationship between patients' baseline and changes in functioning and caregivers' subjective and objective burden as well as their health. Design and Methods: Only stroke patients who had caregivers were included in this analysis (N = 356). Stroke patients In = 281) or their proxies (n = 75) were interviewed within 4 months of hospital discharge and patients' medical records were abstracted. The primary caregiver also was interviewed at approximately the same time as the patient or proxy (N = 356). In all but one of the 75 proxy cases, the proxy was the. patient's caregiver. Binomial and ordinal logistic regression models were used. Results: Declining patient neurological functioning predicted greater objective burden and subjective burden relating to consequences for caregivers' personal lives, but it did not predict caregiver health. Implications: The impact a patient's stroke has on a caregiver's personal life and the number of hours spent caring for the patient appear to be a function of the changes of the patient's status over time rather than a function of a "snapshot" of their functioning at baseline. If these results are confirmed, interventions to protect caregivers may be indicated for stroke patients who continue to decline after hospital discharge. C1 [Nelson, Melissa M.] Univ Minnesota, Div Hlth Policy & Management, Minneapolis, MN USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Martinson, Brian C.] HealthPartners Res Fdn, Minneapolis, MN USA. [Kind, Amy] US Dept Vet Affairs, William S Middleton Hosp, Madison, WI USA. [Kind, Amy] Univ Wisconsin, Dept Med, Geriatr Sect, Madison, WI 53706 USA. [Luepker, Russell V.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Nelson, MM (reprint author), Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, 30 Coll Ave, New Brunswick, NJ 08901 USA. EM mnelson@ifh.rutgers.edu RI Garrido, Melissa/F-2885-2010; OI Garrido, Melissa/0000-0002-8986-3536 FU AHRQ HHS [T32 HS-000036, T32 HS000036]; NINDS NIH HHS [R01-NS39028-01A1, R01 NS039028, R01 NS039028-01A1] NR 41 TC 12 Z9 13 U1 6 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 IS 5 BP 573 EP 583 PG 11 WC Gerontology SC Geriatrics & Gerontology GA 372RQ UT WOS:000260919700002 PM 18981274 ER PT J AU Mavandadi, S Klaus, J Oslin, D AF Mavandadi, S. Klaus, J. Oslin, D. TI THE BEHAVIORAL HEALTH LABORATORY: APPLICATION AND EVALUATION OF A CLINICAL SERVICE FOR BEHAVIORAL HEALTH IN PRIMARY CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mavandadi, S.; Klaus, J.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Oslin, D.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 585 EP 585 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602287 ER PT J AU Clark, P Lees, F Greaney, M Greene, G Riebe, D AF Clark, P. Lees, F. Greaney, M. Greene, G. Riebe, D. TI RESILIENCE IN EXERCISE AND DIET: FACTORS PREDICTING "GETTING BACK ON TRACK" IN A COMMUNITY-DWELLING OLDER ADULT POPULATION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Clark, P.; Lees, F.; Greene, G.; Riebe, D.] Univ Rhode Isl, Kingston, RI 02881 USA. [Greaney, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 587 EP 587 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602295 ER PT J AU Kimbell, K Kimbell, A AF Kimbell, K. Kimbell, A. TI END-OF-LIFE PREPARATIONS MADE BY PRE- AND EARLY-RETIREES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kimbell, K.] Univ Texas Austin, Sch Social Work, Austin, TX 78712 USA. [Kimbell, A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 604 EP 604 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602355 ER PT J AU Williams, BR Ekundayo, J Ritchie, C Ahmed, A AF Williams, B. R. Ekundayo, J. Ritchie, C. Ahmed, A. TI WIDOWHOOD AND MORTALITY IN COMMUNITY DWELLING OLDER ADULTS: A PROPENSITY-MATCHED PROSPECTIVE POPULATION-BASED STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Williams, B. R.; Ritchie, C.] Birmingham Atlanta VA GRECC, Birmingham, AL USA. [Williams, B. R.] UAB, Dept Med, Birmingham, AL USA. [Ritchie, C.] UAB, Ctr Aging, Birmingham, AL USA. [Ahmed, A.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 617 EP 618 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602401 ER PT J AU Phillips, L AF Phillips, L. TI PREDICTING QUALITY OF LIFE AND TRUST IN HEALTHCARE AMONG OLDER MALE INMATES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Phillips, L.] Michael DeBakey Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 677 EP 677 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602605 ER PT J AU Kono, A Fujita, T Kondo, T Tsumura, C Kushiyama, K Rubenstein, L AF Kono, A. Fujita, T. Kondo, T. Tsumura, C. Kushiyama, K. Rubenstein, L. TI A PREVENTIVE HOME VISIT PROGRAM TARGETED TO SPECIFIC CARE-NEEDS OF AMBULATORY FRAIL ELDERS: PILOT RESULTS FROM A RANDOMIZED CONTROLLED TRIAL (RCT) SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kondo, T.] Osaka City Univ, Sch Nursing, Osaka, CA 558, Japan. [Tsumura, C.] Izumiotsu Community Based Comprehens Care Ctr, Izumiotsu, CA, Japan. [Tsumura, C.] Konan Womens Univ, Sch Nursing & Rehabil, Kobe, CA, Japan. [Kushiyama, K.] Misaki Town Goverment Off, Dept Hlth & Welf, Osaka, CA, Japan. [Rubenstein, L.] GRECC & UCLA, VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 726 EP 726 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602778 ER PT J AU Bolkan, C Coehlo, D Hooker, K AF Bolkan, C. Coehlo, D. Hooker, K. TI SELF-REGULATORY FOCUS AND HEALTH-RELATED POSSIBLE SELVES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bolkan, C.] VA Puget Sound, Seattle, WA USA. [Bolkan, C.] Univ Washington, Seattle, WA 98195 USA. [Coehlo, D.] Oregon State Univ Cascades, Bend, OR USA. [Hooker, K.] Oregon State Univ, Coll Hlth & Human Sci, Corvallis, OR 97331 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 751 EP 751 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602862 ER PT J AU Gleason, C AF Gleason, C. TI CLINICAL SCREENING AND EVALUATION OF DRIVING IN PATIENTS WITH DEMENTIA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Gleason, C.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 754 EP 754 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602875 ER PT J AU Hausmann, LRM Levine, JM Higgins, ET AF Hausmann, Leslie R. M. Levine, John M. Higgins, E. Tory TI Communication and group perception: Extending the 'saying is believing' effect SO GROUP PROCESSES & INTERGROUP RELATIONS LA English DT Article DE communication; group perception; saying is believing; shared reality; stereotype development ID MESSAGE MODIFICATION; SOCIAL STEREOTYPES; GROUP DECISION; MEMORY; CONSENSUS; CONSEQUENCES; IMPRESSIONS; FRAMEWORK; AUDIENCE; INFORMATION AB The saying-is-believing (SIB) effect occurs when tailoring a message to suit an audience influences a communicator's subsequent memories and impressions about the communication topic. Previous studies were restricted to one-person audiences and individuals as the communication topic. The present studies explored the SIB effect with multiple-person audiences and groups as the communication topic. In Study 1, the SIB effect occurred with a 1-person, but not a 3-person, audience. In Study 2, the SIB effect occurred with a 3-person audience when the audience explicitly validated communicators' messages. These findings demonstrate the generalizability of the SIB effect to group contexts, provide further evidence for a shared reality interpretation of this effect, and suggest a potentially important mechanism underlying stereotype development. C1 [Hausmann, Leslie R. M.] Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. [Levine, John M.] Univ Pittsburgh, Ctr Learning Res & Dev, Pittsburgh, PA 15260 USA. [Higgins, E. Tory] Columbia Univ, New York, NY 10027 USA. RP Hausmann, LRM (reprint author), Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM leslie.hausmann@gmail.com NR 59 TC 15 Z9 16 U1 1 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1368-4302 J9 GROUP PROCESS INTERG JI Group Process Intergroup Relat. PD OCT PY 2008 VL 11 IS 4 BP 539 EP 554 DI 10.1177/1368430208095405 PG 16 WC Psychology, Social SC Psychology GA 351QT UT WOS:000259440100009 ER PT J AU Feldmann, G Habbe, N Dhara, S Bisht, S Alvarez, H Fendrich, V Beaty, R Mullendore, M Karikari, C Bardeesy, N Ouellette, MM Yu, W Maitra, A AF Feldmann, G. Habbe, N. Dhara, S. Bisht, S. Alvarez, H. Fendrich, V. Beaty, R. Mullendore, M. Karikari, C. Bardeesy, N. Ouellette, M. M. Yu, W. Maitra, A. TI Hedgehog inhibition prolongs survival in a genetically engineered mouse model of pancreatic cancer SO GUT LA English DT Article ID UROKINASE PLASMINOGEN-ACTIVATOR; HIGHLY EXPRESSED GENES; FACTOR-KAPPA-B; DUCTAL ADENOCARCINOMA; IN-VITRO; COMPREHENSIVE CHARACTERIZATION; EPITHELIAL-CELLS; CDNA MICROARRAY; GROWTH; OVEREXPRESSION AB Background and aims: Pancreatic cancer is among the most dismal of human malignancies. Current therapeutic strategies are virtually ineffective in controlling advanced, metastatic disease. Recent evidence suggests that the Hedgehog signalling pathway is aberrantly reactivated in the majority of pancreatic cancers, and that Hedgehog blockade has the potential to prevent disease progression and metastatic spread. Methods: Here it is shown that the Hedgehog pathway is activated in the Pdx1-Cre; LsL-Kras(G12D); Ink4a/Arf(lox/lox) transgenic mouse model of pancreatic cancer. The effect of Hedgehog pathway inhibition on survival was determined by continuous application of the small molecule cyclopamine, a smoothened antagonist. Microarray analysis was performed on non-malignant human pancreatic ductal cells overexpressing Gli1 in order to screen for downstream Hedgehog target genes likely to be involved in pancreatic cancer progression. Results: Hedgehog inhibition with cyclopamine significantly prolonged median survival in the transgenic mouse model used here (67 vs 61 days; p= 0.026). In vitro data indicated that Hedgehog activation might at least in part be ascribed to oncogenic Kras signalling. Microarray analysis identified 26 potential Hedgehog target genes that had previously been found to be overexpressed in pancreatic cancer. Five of them, BIRC3, COL11A1, NNMT, PLAU and TGM2, had been described as upregulated in more than one global gene expression analysis before. Conclusion: This study provides another line of evidence that Hedgehog signalling is a valid target for the development of novel therapeutics for pancreatic cancer that might be worth evaluating soon in a clinical setting. C1 [Feldmann, G.; Habbe, N.; Dhara, S.; Bisht, S.; Alvarez, H.; Beaty, R.; Mullendore, M.; Karikari, C.; Maitra, A.] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21210 USA. [Dhara, S.] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Radiol, Baltimore, MD 21210 USA. [Fendrich, V.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Fendrich, V.] Univ Marburg, Dept Surg, Marburg, Germany. [Beaty, R.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Bardeesy, N.] Harvard Univ, Sch Med, Ctr Canc, Massachusetts Gen Hosp, Boston, MA USA. [Ouellette, M. M.] Univ Nebraska Med Ctr, Eppley Inst Res Canc, Omaha, NE USA. [Yu, W.] Johns Hopkins Univ, Sch Med, DNA Microarray Core Facil, Baltimore, MD USA. RP Feldmann, G (reprint author), Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Canc Res Bldg 2,Room 316,1550 Orleans St, Baltimore, MD 21210 USA. EM gfeldma4@jhmi.edu FU ol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Foundation, NIH SPORE (Specialized Programs of Research Excellence) in Gastrointestinal Cancer [P50CA62924]; NIH [R01CA113669] FX Supported by the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Foundation, NIH SPORE (Specialized Programs of Research Excellence) in Gastrointestinal Cancer P50CA62924 and NIH R01CA113669 to AM. GF was supported by a fellowship grant within the postdoc- programme of the German Academic Exchange Service (DAAD). HA received generous support from the D'Amato Family. NR 57 TC 104 Z9 112 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD OCT PY 2008 VL 57 IS 10 BP 1420 EP 1430 DI 10.1136/gut.2007.148189 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 348GK UT WOS:000259198800020 PM 18515410 ER PT J AU Biggs, PJ Styczynski, JR AF Biggs, Peter J. Styczynski, John R. TI Do angles of obliquity apply to 30 degrees scattered radiation from megavoltage beams? SO HEALTH PHYSICS LA English DT Article DE accelerators, medical; bremsstrahlung; radiation, gamma; radiation, medical ID MV X-RAYS; 0-DEGREES; CONCRETE; CO-60 AB The angle of obliquity is used in radiation shielding calculations to account for the longer path length x rays will see when obliquely incident on the protective barrier. According to the National Council on Radiation Protection and Measurements (NCRP), use of the angle of obliquity is explicitly assumed for primary radiation, so that an angle of obliquity for secondary radiation is never addressed. However, in the example section of the latest report, it specifically recommends against using an angle of obliquity for scattered radiation. To check this assumption, the existence or not of an angle of obliquity for scattered radiation has been investigated for bremsstrahlung x-ray beams of 4,6,10,15, and 18 MV and for barriers consisting of concrete, lead, and steel using a Monte Carlo approach. The MCNP Monte Carlo code, v4.2C, has been used to generate scattered radiation at 30 degrees from a water phantom and incident on a secondary barrier at the same angle relative to the normal to the barrier. The barrier thickness was increased from zero to a thickness sufficient to reduce the fluence (f4 tally) to < 10(-3). A transmission curve was created for each energy-barrier material combination by normalizing to zero thickness. The results for the first tenth-value layer (TVL) in concrete (5 energies) show an average angle of obliquity of 21.7 degrees +/- 5.6 degrees, and for the first two TVLs averaged 29.7 degrees +/- 3.9 degrees. The results for the first TVL in lead (3 energies) show an average angle of obliquity of 27.7 degrees +/- 4.0 degrees, and for the first two TVLs averaged 20.5 degrees +/- 5.8 degrees. There are no data in the NCRP reports for 30 degrees scattered radiation attenuated by steel with which to make a comparison. C1 [Biggs, Peter J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Styczynski, John R.] MIT, Cambridge, MA 02138 USA. RP Biggs, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM pjbiggs@partners.org RI STYCZYNSKI, JAN/D-3922-2014 OI STYCZYNSKI, JAN/0000-0002-3158-119X NR 9 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD OCT PY 2008 VL 95 IS 4 BP 425 EP 432 DI 10.1097/01.HP.0000319905.27506.88 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 350KA UT WOS:000259350100005 PM 18784515 ER PT J AU Werner, RM Bradlow, ET Asch, DA AF Werner, Rachel M. Bradlow, Eric T. Asch, David A. TI Does hospital performance on process measures directly measure high quality care or is it a marker of unmeasured care? SO HEALTH SERVICES RESEARCH LA English DT Article DE quality of care; quality improvement; performance measurement; process measures ID ACUTE MYOCARDIAL-INFARCTION; COMMUNITY-ACQUIRED PNEUMONIA; PRACTICE GUIDELINES COMMITTEE; LEFT-VENTRICULAR DYSFUNCTION; ASSOCIATION TASK-FORCE; HEART-FAILURE; AMERICAN-COLLEGE; MORTALITY-RATES; ACC/AHA GUIDELINES; RANDOMIZED-TRIAL AB Objective. Quality measures may be associated with improved outcomes for two reasons. First, measured activities may directly improve care. Second, success on these measures may be a marker for other unmeasured aspects of high quality care. Our objective is to test the contribution of both possible effects. Data Sources. 2004 Medicare data on hospital performance from Hospital Compare and risk-adjusted mortality rates from Medicare Part A claims. Study Design. We studied 3,657 acute care U.S. hospitals and compared observed differences in condition-specific hospital mortality rates based on hospital performance with expected differences in mortality from the clinical studies underlying the measures. Principal Findings. Differences in observed mortality rates across U.S. hospitals are larger than what would be expected if these differences were due only to the direct effects of delivering measured care. Conclusions. Performance measures reflect care processes that both improve care directly and are also markers of elements of health care quality that are otherwise unmeasured. This finding suggests that process measures capture important information about care that is not directly measured, and that these unmeasured effects are in general larger than the measured effects. C1 [Werner, Rachel M.; Asch, David A.] Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Werner, Rachel M.; Asch, David A.] Univ Penn, VA Div Gen Internal Med, Philadelphia, PA 19104 USA. [Werner, Rachel M.; Bradlow, Eric T.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Bradlow, Eric T.] Univ Penn, Dept Marketing, Philadelphia, PA 19104 USA. [Bradlow, Eric T.] Univ Penn, Dept Stat, Philadelphia, PA 19104 USA. [Bradlow, Eric T.] Univ Penn, Dept Educ, Philadelphia, PA 19104 USA. RP Werner, RM (reprint author), 1230 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 55 TC 27 Z9 27 U1 4 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2008 VL 43 IS 5 BP 1464 EP 1484 DI 10.1111/j.1475-6773.2007.00817.x PN 1 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 350HR UT WOS:000259343800002 PM 22568614 ER PT J AU Donohue, JM Fischer, MA Huskamp, HA Weissman, JS AF Donohue, Julie M. Fischer, Michael A. Huskamp, Haiden A. Weissman, Joel S. TI Potential savings from an evidence-based consumer-oriented public education campaign on prescription drugs SO HEALTH SERVICES RESEARCH LA English DT Article DE prescription drugs; costs; consumer; education; evidence-based medicine ID CONVERTING-ENZYME-INHIBITORS; GENERIC DRUGS; NATIONAL-SURVEY; BRAND-NAME; BENEFITS; CARE; PHARMACEUTICALS; COVERAGE; IMPACT; BENEFICIARIES AB Objective. To estimate potential savings associated with the Consumer Reports Best Buy Drugs program, a national educational program that provides consumers with price and effectiveness information on prescription drugs. Data Sources. National data on 2006 prescription sales and retail prices paid for angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers, calcium channel blockers, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-coA) reductase inhibitors (statins). Study Design. We converted national data on aggregate unit sales of drugs in the four classes to defined daily doses (DDD) and estimated a range of potential savings from generic and therapeutic substitution. Principal Findings. We estimated that $2.76 billion, or 7.83 percent of sales, could be saved if use of the drugs recommended by the educational program was increased. The recommended drugs' prices were 15-65 percent lower per DDD than their therapeutic alternatives. The majority (57.4 percent) of potential savings would be achieved through therapeutic substitution. Conclusions. Substantial savings can be achieved through greater use of comparatively effective and lower cost drugs recommended by a national consumer education program. However, barriers to dissemination of consumer-oriented drug information must be addressed before savings can be realized. C1 [Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15261 USA. [Fischer, Michael A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Huskamp, Haiden A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Weissman, Joel S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Donohue, JM (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, 130 DeSoto St,Crabtree Hall A613, Pittsburgh, PA 15261 USA. EM jdonohue@pitt.edu RI Mendoza, Elvia/A-9361-2012; OI Donohue, Julie/0000-0003-2418-6017 FU Consumers Union; Engelberg Foundation; National Library of Medicine FX The authors wish to thank Steve Findlay and Gail Shearer of Consumers Union for helpful comments on earlier drafts of this manuscript. We also wish to thank Keith Newsom-Stewart at Consumers Union for valuable assistance with data collection. The authors received grant funding from Consumers Union to evaluate selected aspects of the Consumer Reports Best Buy Drugs program. The Consumer Reports Best Buy Drugs program is supported by grants from the Engelberg Foundation and the National Library of Medicine. NR 57 TC 5 Z9 5 U1 2 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2008 VL 43 IS 5 BP 1557 EP 1575 DI 10.1111/j.1475-6773.2008.00858.x PN 1 PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 350HR UT WOS:000259343800007 PM 18479406 ER PT J AU Yano, EM Rubenstein, LV Farmer, MM Chernof, BA Mittman, BS Lanto, AB Simon, BF Lee, ML Sherman, SE AF Yano, Elizabeth M. Rubenstein, Lisa V. Farmer, Melissa M. Chernof, Bruce A. Mittman, Brian S. Lanto, Andrew B. Simon, Barbara F. Lee, Martin L. Sherman, Scott E. TI Targeting primary care referrals to smoking cessation clinics does not improve quit rates: Implementing evidence-based interventions into practice SO HEALTH SERVICES RESEARCH LA English DT Article DE smoking cessation; quality of health care; veterans ID QUALITY IMPROVEMENT; TOBACCO CESSATION; PRACTICE GUIDELINE; RANDOMIZED-TRIAL; AHCPR GUIDELINE; HEALTH; DEPRESSION; SMOKERS; RECOMMENDATIONS; COLLABORATIVES AB Objective. To evaluate the impact of a locally adapted evidence-based quality improvement (EBQI) approach to implementation of smoking cessation guidelines into routine practice. Data Sources/Study Setting. We used patient questionnaires, practice surveys, and administrative data in Veterans Health Administration (VA) primary care practices across five southwestern states. Study Design. In a group-randomized trial of 18 VA facilities, matched on size and academic affiliation, we evaluated intervention practices' abilities to implement evidence-based smoking cessation care following structured evidence review, local priority setting, quality improvement plan development, practice facilitation, expert feedback, and monitoring. Control practices received mailed guidelines and VA audit-feedback reports as usual care. Data Collection. To represent the population of primary care-based smokers, we randomly sampled and screened 36,445 patients to identify and enroll eligible smokers at baseline (n=1,941) and follow-up at 12 months (n=1,080). We used computer-assisted telephone interviewing to collect smoking behavior, nicotine dependence, readiness to change, health status, and patient sociodemographics. We used practice surveys to measure structure and process changes, and administrative data to assess population utilization patterns. Principal Findings. Intervention practices adopted multifaceted EBQI plans, but had difficulty implementing them, ultimately focusing on smoking cessation clinic referral strategies. While attendance rates increased (p <.0001), we found no intervention effect on smoking cessation. Conclusions. EBQI stimulated practices to increase smoking cessation clinic referrals and try other less evidence-based interventions that did not translate into improved quit rates at a population level. C1 [Yano, Elizabeth M.] Sepulveda VA Ambulatory Care Ctr 152, VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA 91343 USA. [Rubenstein, Lisa V.] VA Greater Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Rubenstein, Lisa V.] RAND Hlth, Santa Monica, CA USA. [Yano, Elizabeth M.; Farmer, Melissa M.; Mittman, Brian S.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Chernof, Bruce A.] Los Angeles Cty Dept Hlth Serv, Los Angeles, CA USA. [Lee, Martin L.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. RP Yano, EM (reprint author), Sepulveda VA Ambulatory Care Ctr 152, VA Greater Los Angeles HSR&D Ctr Excellence, 16111 Plummer St, Sepulveda, CA 91343 USA. EM elizabeth.yano@va.gov OI Mittman, Brian/0000-0003-3589-9178; Sherman, Scott/0000-0003-1752-7303 FU the VA HSRD Service [CPG 97-012]; VA HSRD [MRP 04-221, RCS 05-195]; the VA Greater Los Angeles HSR& D Center of Excellence [HFP 94-028] FX This study was funded by the VA HSR&D Service (Project #CPG 97-012). The trial was registered through ClinicalTrials.gov (Registry No. NCT00012987). Dr. Farmer was supported ;by a VA HSR&D career development award (Project # MRP 04-221). Dr. Yano was supported by the original grant, and subsequently by the VA Greater Los Angeles HSR& D Center of Excellence (Project #HFP 94-028) and a VA HSR& D Research Career Scientist Award (Project #RCS 05-195). We acknowledge the support of our site principal investigators: Timothy Carmody, Ph. D., Carol Chavez, N. P., Linda Ferry, M. D., Michael Gould, M. D., Betty Hedrick, N. P., Linda Hill, R. N., James Howard, M. D., Susan Blair Knepper, F. N. P., Charles McCreary, M. D., Matthew Meyer, Ph. D., Celia Michael, Ph. D., Nicole Miller, Ph. D., Sharon Rapp, Ph. D., Mitch Rice, R. N., M. N., Robert Smyer, M. D., David Webb, M. D., Brian Yee, M. D., and Sheila Young, Ph. D. We also acknowledge MingMing Wang, M. P. H., for administrative data acquisition and analysis, Ismelda Canelo, M. P. A., for administrative support, and the many interviewers and staff at California Survey Research Services Inc. (CSRS) in Van Nuys, CA. We would also like to thank the editors and reviewers for their extremely helpful, substantive input leading to improved reporting of these trial results. NR 68 TC 14 Z9 14 U1 4 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2008 VL 43 IS 5 BP 1637 EP 1661 DI 10.1111/j.1475-6773.2008.00865.x PN 1 PG 25 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 350HR UT WOS:000259343800011 PM 18522670 ER PT J AU Iezzoni, LI Ngo, LH Li, D Roetzheim, RG Drews, RE McCarthy, EP AF Iezzoni, Lisa I. Ngo, Long H. Li, Donglin Roetzheim, Richard G. Drews, Reed E. McCarthy, Ellen P. TI Early stage breast cancer treatments for younger medicare beneficiaries with different disabilities SO HEALTH SERVICES RESEARCH LA English DT Article DE breast cancer; disability; disparities ID QUALITY-OF-LIFE; PREVENTIVE SERVICES; RADICAL-MASTECTOMY; CONSERVING SURGERY; MAMMOGRAPHY RATES; WOMEN; POPULATION; DISORDERS; CARCINOMA; HEALTH AB Objective. To explore how underlying disability affects treatments and outcomes of disabled women with breast cancer. Data Sources. Surveillance, Epidemiology, and End Results program data, linked with Medicare files and Social Security Administration disability group. Study Design. Ninety thousand two hundred and forty-three incident cases of early-stage breast cancer under age 65; adjusted relative risks and hazards ratios examined treatments and survival, respectively, for women in four disability groups compared with nondisabled women. Principal Findings. Demographic characteristics, treatments, and survival varied among four disability groups. Compared with nondisabled women, those with mental disorders and neurological conditions had significantly lower adjusted rates of breast conserving surgery and radiation therapy. Survival outcomes also varied by disability type. Conclusions. Compared with nondisabled women, certain subgroups of women with disabilities are especially likely to experience disparities in care for breast cancer. C1 [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Div Med, Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa I.; Ngo, Long H.; Drews, Reed E.; McCarthy, Ellen P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ngo, Long H.; Li, Donglin; McCarthy, Ellen P.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Roetzheim, Richard G.] Univ S Florida, Dept Family Med, Tampa, FL USA. [Drews, Reed E.] Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Div Med, Inst Hlth Policy, 50 Staniford St,Rm 901C, Boston, MA 02114 USA. EM liezzoni@partners.org RI Roetzheim, Richard/J-4696-2012 FU National Cancer Institute [R01 CA100029] FX The National Cancer Institute funded this research (R01 CA100029). NR 36 TC 12 Z9 12 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2008 VL 43 IS 5 BP 1752 EP 1767 DI 10.1111/j.1475-6773.2008.00853.x PN 1 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 350HR UT WOS:000259343800018 PM 18479411 ER PT J AU Ferreira, AC Isomoto, H Moriyama, M Fujioka, T Machado, JC Yamaoka, Y AF Ferreira, Antonio Carlos Isomoto, Hajime Moriyama, Masatsugu Fujioka, Toshio Machado, Jose Carlos Yamaoka, Yoshio TI Helicobacter and gastric malignancies SO HELICOBACTER LA English DT Article DE Helicobacter pylori; gastric cancer; MALT lymphoma ID LYMPHOID-TISSUE LYMPHOMAS; IN-SITU HYBRIDIZATION; BETA-CATENIN SIGNAL; MALT LYMPHOMA; PYLORI ERADICATION; PROMOTER HYPERMETHYLATION; E-CADHERIN; ATROPHIC GASTRITIS; PEPTIC-ULCERATION; EPITHELIAL-CELLS AB Individuals infected with Helicobacter pylori, a stomach colonizing bacteria, have an increased risk of developing gastric malignancies. The risk for developing cancer relates to the physiologic and histologic changes that H. pylori infection induces in the stomach. In the last year numerous studies have been conducted in order to characterize the association between H. pylori infection and gastric cancer. These studies range from epidemiologic approaches aiming at the identification of environmental, host genetic, and bacterial factors associated with risk of gastric cancer, to molecular and cell biology approaches aiming at understanding the interaction between H. pylori and the transforming epithelial cell. In this review an account of the last year's research activity on the relationship between H. pylori and gastric cancer will be given. C1 [Ferreira, Antonio Carlos; Machado, Jose Carlos] Univ Porto, IPATIMUP Inst Mol Pathol & Immunol, Fac Med, P-4100 Oporto, Portugal. [Isomoto, Hajime] Nagasaki Univ, Sch Med, Dept Endoscopy, Nagasaki 852, Japan. [Moriyama, Masatsugu] Oita Univ, Dept Mol Pathol, Yufu City, Oita 8795593, Japan. [Fujioka, Toshio] Oita Univ, Fac Med, Dept Gastroenterol, Yufu City, Oita 8795593, Japan. [Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA. [Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA. RP Machado, JC (reprint author), IPATIMUP, Rua Dr Roberto Frias S-N, P-4200465 Oporto, Portugal. EM josem@ipatimup.pt RI Machado, Jose Carlos/C-5907-2009 OI Machado, Jose Carlos/0000-0003-4741-8415 FU NIDDK NIH HHS [R01 DK062813, R01 DK062813-05, R0I DK 62813] NR 51 TC 32 Z9 41 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD OCT PY 2008 VL 13 SU 1 BP 28 EP 34 DI 10.1111/j.1523-5378.2008.00633.x PG 7 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 335AL UT WOS:000258263100006 PM 18783519 ER PT J AU Graham, DY Kwon, DH AF Graham, D. Y. Kwon, D. H. TI Genome-scale transcriptional modulation in response to metronidazole stress in metronidazole resistant and susceptible H-pylori SO HELICOBACTER LA English DT Meeting Abstract CT 21st International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation and Gastric Cancer CY SEP 18-20, 2008 CL Riga, LATVIA C1 [Graham, D. Y.; Kwon, D. H.] Baylor Coll Med, Houston, TX 77030 USA. [Graham, D. Y.; Kwon, D. H.] VA Med Ctr, Houston, TX USA. [Kwon, D. H.] Long Isl Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD OCT PY 2008 VL 13 IS 5 BP 409 EP 409 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 336ZF UT WOS:000258404600057 ER PT J AU Ohno, T Backstrom, A Arnqvist, A Rugge, M Ota, H Graham, DY Yamaoka, Y AF Ohno, T. Backstrom, A. Arnqvist, A. Rugge, M. Ota, H. Graham, D. Y. Yamaoka, Y. TI Changes in H-pylori adherence properties during long-term Mongolian gerbil infection SO HELICOBACTER LA English DT Meeting Abstract CT 21st International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation and Gastric Cancer CY SEP 18-20, 2008 CL Riga, LATVIA C1 [Ohno, T.; Graham, D. Y.; Yamaoka, Y.] ME DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Ohno, T.; Graham, D. Y.; Yamaoka, Y.] Baylor Coll Med, Houston, TX 77030 USA. [Backstrom, A.] Umea Univ, Dept Odontol Oral Microbiol, Umea, Sweden. [Backstrom, A.; Arnqvist, A.] Umea Univ, Dept Med Biochem & Biophys, Umea, Sweden. [Rugge, M.] Univ Padua, Dept Diagnost Sci & Special Therapies, Pathol Unit, Padua, Italy. [Ota, H.] Shinshu Univ, Sch Med, Sch Hlth Sci, Dept Biomed Lab Sci, Matsumoto, Nagano 390, Japan. RI Rugge, Massimo/K-7525-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD OCT PY 2008 VL 13 IS 5 BP 410 EP 410 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 336ZF UT WOS:000258404600061 ER PT J AU Sugimoto, M Sakai, K Kita, M Imanishi, J Yamaoka, Y AF Sugimoto, M. Sakai, K. Kita, M. Imanishi, J. Yamaoka, Y. TI Prevalence of H-pylori infection in patients receiving long-term Hemodialysis SO HELICOBACTER LA English DT Meeting Abstract CT 21st International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation and Gastric Cancer CY SEP 18-20, 2008 CL Riga, LATVIA C1 [Sugimoto, M.; Yamaoka, Y.] Baylor Coll Med, Houston, TX 77030 USA. [Sugimoto, M.; Yamaoka, Y.] ME DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Sakai, K.] Nara City Hosp, Dept Gastroenterol & Hepatol, Nara, Japan. [Kita, M.; Imanishi, J.] Kyoto Prefectural Univ Med, Dept Microbiol, Kyoto 602, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD OCT PY 2008 VL 13 IS 5 BP 439 EP 439 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 336ZF UT WOS:000258404600142 ER PT J AU Imamura, S Yamaoka, Y Sumida, Y Kanemasa, K AF Imamura, S. Yamaoka, Y. Sumida, Y. Kanemasa, K. TI H-pylori infection protects against allergic diseases SO HELICOBACTER LA English DT Meeting Abstract CT 21st International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation and Gastric Cancer CY SEP 18-20, 2008 CL Riga, LATVIA C1 [Imamura, S.] Aiseikai Yamashina Hosp, Kyoto, Japan. [Yamaoka, Y.] Baylor Coll Med, Houston, TX 77030 USA. [Yamaoka, Y.] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. [Sumida, Y.; Kanemasa, K.] Nara City Hosp, Nara, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD OCT PY 2008 VL 13 IS 5 BP 441 EP 441 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 336ZF UT WOS:000258404600147 ER PT J AU Weisbord, SD Bossola, M Fried, LF Giungi, S Tazza, L Palevsky, PM Arnold, RM Luciani, G Kimmel, PL AF Weisbord, Steven D. Bossola, Maurizio Fried, Linda F. Giungi, Stefania Tazza, Luigi Palevsky, Paul M. Arnold, Robert M. Luciani, Giovanna Kimmel, Paul L. TI Cultural comparison of symptoms in patients on maintenance hemodialysis SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE cross-cultural; hemodialysis; symptoms; quality of life ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; ERECTILE DYSFUNCTION; DIALYSIS PATIENTS; PSYCHOSOCIAL FACTORS; SEXUAL DYSFUNCTION; ASSESSMENT SYSTEM; KIDNEY-DISEASE; MINI-COG; DEPRESSION AB Although symptoms are common and frequently severe in patients on maintenance hemodialysis, little is known about the relationship between cultural background and symptom burden. The aim of this study was to explore differences in the prevalence and severity of symptoms between American and Italian hemodialysis patients. We administered the 30-item Dialysis Symptom Index to American and Italian patients receiving maintenance hemodialysis during routine dialysis sessions. The prevalence and severity of individual symptoms were compared between patient populations, adjusting for multiple comparisons. Multivariable logistic regression and ordinal logistic regression were used to assess the independent associations of cultural background with the prevalence and severity of symptoms, respectively. We enrolled 75 American and 61 Italian patients. American patients were more likely to be black (36% vs. 0%, P < 0.001) and diabetic (53% vs. 13%, P < 0.001). Italian patients were more likely to report decreased interest in sex, decreased sexual arousal, feeling nervous, feeling irritable, and worrying (P < 0.001, respectively). Adjustment for demographic and clinical variables had no impact on these cultural differences in symptom prevalence. The median severity of 11 symptoms including muscle soreness, muscle cramps, and itching was greater among Americans (P < 0.001, respectively), although nearly all of these differences were rendered nonstatistically significant with adjustment for race, diabetes, and/or Kt/V. Italian patients receiving chronic hemodialysis report a greater burden of symptoms than American patients, particularly those related to sexual dysfunction and psychosocial distress. These findings suggest that cultural background may affect adaptation to chronic hemodialysis therapy. C1 [Weisbord, Steven D.; Fried, Linda F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Fried, Linda F.; Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Fried, Linda F.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Bossola, Maurizio; Giungi, Stefania; Tazza, Luigi; Luciani, Giovanna] Catholic Univ, Dept Surg, Dialysis Unit, Rome, Italy. [Arnold, Robert M.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Inst Enhance Palliat Care, Pittsburgh, PA USA. [Kimmel, Paul L.] George Washington Univ, Sch Med, Div Renal Dis & Hypertens, Washington, DC USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Mailstop 111F-U,7E Room 120, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu FU Institute to Enhance Palliative Care at the University of Pittsburgh; VA Health Services Research and Development Career Development Award [RCD 03-176] FX Dr Weisbord was supported by a grant from the Institute to Enhance Palliative Care at the University of Pittsburgh and a VA Health Services Research and Development Career Development Award (RCD 03-176). Although some of the data in the 3 tables has been published previously in the Clinical Journal of the American Society of Nephrology, the content and results specific to this study have not been published previously. NR 34 TC 9 Z9 9 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1492-7535 J9 HEMODIAL INT JI Hemodial. Int. PD OCT PY 2008 VL 12 IS 4 BP 434 EP 440 DI 10.1111/j.1542-4758.2008.00307.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 357RN UT WOS:000259864000006 PM 19090866 ER PT J AU Yagi, H Suganuma, K Parekkadan, B Soto-Gutierrez, AD Kitagawa, Y Kitajima, M Toner, M Tompkins, RG Berthiaume, F Tilles, AW Yarmush, ML AF Yagi, Hiroshi Suganuma, Kazuhiro Parekkadan, Biju Soto-Gutierrez, Alejan-dro Kitagawa, Yuko Kitajima, Masaki Toner, Mehmet Tompkins, Ronald G. Berthiaume, Francois Tilles, Arno W. Yarmush, Martin L. TI THERAPEUTIC POTENTIAL OF HUMAN BONE MARROW-DERIVED STEM CELL BASED LIVER-ASSIST DEVICE FOR FULMINANT HEPATIC FAILURE SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Yagi, Hiroshi; Parekkadan, Biju; Soto-Gutierrez, Alejan-dro; Toner, Mehmet; Tompkins, Ronald G.; Berthiaume, Francois; Tilles, Arno W.; Yarmush, Martin L.] Massachusetts Gen Hosp, Charlestown, MA USA. [Suganuma, Kazuhiro; Kitagawa, Yuko] Keio Univ, Sch Med, Tokyo, Japan. [Yagi, Hiroshi; Soto-Gutierrez, Alejan-dro; Toner, Mehmet; Tompkins, Ronald G.; Berthiaume, Francois; Tilles, Arno W.; Yarmush, Martin L.] Harvard Univ, Sch Med, Boston, MA USA. [Kitajima, Masaki] Int Univ Hlth & Welf, Tokyo, Japan. [Parekkadan, Biju] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 33 BP 323A EP 323A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400032 ER PT J AU Tai, AW Peng, LF Chung, RT AF Tai, Andrew W. Peng, Lee F. Chung, Raymond T. TI A FUNCTIONAL GENOMIC SCREEN IDENTIFIES CELLULAR COFACTORS OF HCV REPLICATION SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Tai, Andrew W.; Peng, Lee F.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, GI Unit, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 59 BP 332A EP 333A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400054 ER PT J AU Goessling, W North, TE Schmitt, S Lord, AM Lee, S Puder, M Moon, RT Daley, G Zon, LI AF Goessling, Wolfram North, Trista E. Schmitt, Sabine Lord, Allegra M. Lee, Sang Puder, Mark Moon, Randall T. Daley, George Zon, Leonard I. TI PROSTAGLANDIN E2 ENHANCES LIVER REGENERATION THROUGH CAMP/PKA-MEDIATED REGULATION OF NUCLEAR beta-CATENIN ACCUMULATION SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Goessling, Wolfram; North, Trista E.; Schmitt, Sabine; Lord, Allegra M.; Daley, George; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Goessling, Wolfram] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Lee, Sang; Puder, Mark] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Moon, Randall T.] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 75 BP 340A EP 340A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400070 ER PT J AU Birch, CE Kim, AY Reyor, LL Bowen, MJ Nagami, EH McGovern, B AF Birch, Christopher E. Kim, Arthur Y. Reyor, Laura L. Bowen, Melinda J. Nagami, Ellen H. McGovern, Barbara TI RAPID VIROLOGIC RESPONSE IS COMMON IN ACUTE HEPATITIS C VIRUS (HCV) INFECTION REGARDLESS OF GENOTYPE SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Birch, Christopher E.; Kim, Arthur Y.; Reyor, Laura L.; Bowen, Melinda J.; Nagami, Ellen H.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kim, Arthur Y.] Harvard Univ, Sch Med, Boston, MA USA. [Birch, Christopher E.; Nagami, Ellen H.] Harvard Ctr AIDS Res, Boston, MA USA. [McGovern, Barbara] Lamuel Shattuck Hosp, Jamaica Plain, MA USA. [McGovern, Barbara] Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 90 BP 346A EP 346A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400083 ER PT J AU Kanwal, F Asch, S Schnitzler, MS Bacon, BR AF Kanwal, Fasiha Asch, Steven Schnitzler, Mark S. Bacon, Bruce R. TI PREDICTORS OF QUALITY CARE AMONG PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Kanwal, Fasiha] St Louis VA Med Ctr, St Louis, MO USA. [Kanwal, Fasiha; Schnitzler, Mark S.] St Louis Univ, Sch Med, St Louis, MO USA. [Asch, Steven] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 118 BP 358A EP 358A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400109 ER PT J AU Rongey, C Kanwal, F Hoang, T Gifford, A Asch, S AF Rongey, Catherine Kanwal, Fasiha Hoang, Tuyen Gifford, Allen Asch, Steven TI PREDICTORS OF VIRAL RNA TESTING IN HEPATITIS C ANTIBODY POSITIVE VETERANS SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Rongey, Catherine] LACUSC, Los Angeles, CA USA. [Rongey, Catherine] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA USA. [Kanwal, Fasiha] St Louis Univ, Ctr Outcomes Res, St Louis, MO 63103 USA. [Hoang, Tuyen] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gifford, Allen] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 119 BP 358A EP 358A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400110 ER PT J AU Kramer, JR Kanwal, F Giordano, TP Richardson, P Petersen, L El-Serag, HB AF Kramer, Jennifer R. Kanwal, Fasiha Giordano, Thomas P. Richardson, Peter Petersen, Laura El-Serag, Hashem B. TI PATIENT, PROVIDER, AND FACILITY CHARACTERISTICS OF HCV ANTIVIRAL TREATMENT AMONG US VETERANS WITH HCV-HIV COINFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Kramer, Jennifer R.; Giordano, Thomas P.; Richardson, Peter; Petersen, Laura; El-Serag, Hashem B.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Kanwal, Fasiha] St Louis Univ, Sch Med, St Louis, MO USA. [Kanwal, Fasiha] St Louis Univ, John Cochran Vet Affairs Med Ctr, St Louis, MO 63103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 121 BP 359A EP 359A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400112 ER PT J AU Wiesch, JSZ Kasprowicz, V Kuntzen, T Nolan, BE Longworth, S Reyor, LL McGovern, B Allen, TM Lohse, AW Lewis-Ximenez, L Kwok, WW Chung, RT Kim, AY Lauer, GM AF Wiesch, Julian Schulze zur Kasprowicz, Victoria Kuntzen, Thomas Nolan, Brian E. Longworth, Steve Reyor, Laura L. McGovern, Barbara Allen, Todd M. Lohse, Ansgar W. Lewis-Ximenez, Lia Kwok, William W. Chung, Raymond T. Kim, Arthur Y. Lauer, Georg M. TI EX VIVO ANALYSIS OF CD4+T HELPER CELL RESPONSES IN ACUTE HCV INFECTION AND EARLY TREATMENT. EARLY ANTIVIRAL THERAPY PRESERVES VIRUS SPECIFIC CD4+CELLS SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Wiesch, Julian Schulze zur; Lohse, Ansgar W.] Univ Hosp Hamburg Eppendorf, Dept Med, Hamburg, Germany. [Wiesch, Julian Schulze zur; Kasprowicz, Victoria; Kuntzen, Thomas; Nolan, Brian E.; Longworth, Steve; Reyor, Laura L.; Allen, Todd M.; Kim, Arthur Y.; Lauer, Georg M.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [McGovern, Barbara] Tufts Med Ctr, Boston, MA USA. [Lewis-Ximenez, Lia] Inst Oswaldo Cruz, Dept Virol, BR-20001 Rio De Janeiro, Brazil. [Nolan, Brian E.; Longworth, Steve; Reyor, Laura L.; Chung, Raymond T.; Lauer, Georg M.] Massachusetts Gen Hosp, Gl Div, Boston, MA 02114 USA. [Kwok, William W.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 206 BP 401A EP 401A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400203 ER PT J AU Nevzorova, Y Moro, N Sicinski, P Gossler, N Trautwein, C Liedtke, C AF Nevzorova, Yulia Moro, Nives Sicinski, Peter Gossler, Nikolaus Trautwein, Christian Liedtke, Christian TI DEPLETION OF CYCLIN E1 AND E2 DIFFERENTIALLY EFFECTS THE INITIATION AND PROGRESSION OF LIVER FIBROSIS SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Nevzorova, Yulia; Moro, Nives; Trautwein, Christian; Liedtke, Christian] Univ Hosp Aachen, Dept Med 3, Aachen, Germany. [Gossler, Nikolaus] Univ Hosp Aachen, Inst Pathol, Aachen, Germany. [Sicinski, Peter] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 251 BP 422A EP 422A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400248 ER PT J AU Kuntzen, T Timm, J Berical, A Berlin, AM Oniangue-Ndza, C Lee, BS Hecker-Man, D Carlson, J Rosen, HR Bihl, FK Cerny, A Spengler, U Liu, ZM Xing, YM Modey, MA Fleckenstein, JF Park, VM Riely, CA Lake-Bakaar, G Daar, ES Jacobson, IM Gomperts, ED Edlin, BR Donfield, SM Chung, RT Talal, A Mar-Ion, TN Birren, BW Henn, MR Allen, TM AF Kuntzen, Thomas Timm, Joerg Berical, Andrew Berlin, Aaron M. Oniangue-Ndza, Cesar Lee, Bongshin Hecker-man, David Carlson, Jonathan Rosen, Hugo R. Bihl, Florian K. Cerny, Andreas Spengler, Ulrich Liu, Zhimin Xing, Yanming Modey, Margret A. Fleckenstein, Jaquelyn F. Park, Vicky M. Riely, Caroline A. Lake-Bakaar, Gerond Daar, Eric S. Jacobson, Ira M. Gomperts, Edward D. Edlin, Brian R. Donfield, Sharyne M. Chung, Raymond T. Talal, Andrew Mar-ion, Tony N. Birren, Bruce W. Henn, Matthew R. Allen, Todd M. TI NATURALLY OCCURRING STAT-C RESISTANCE MUTATIONS IN TREATMENT-NAME HCV INFECTED PATIENTS - AN INTERNATIONAL MULTI-CENTER STUDY SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Kuntzen, Thomas; Berical, Andrew; Oniangue-Ndza, Cesar; Allen, Todd M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. [Timm, Joerg] Essen Univ Hosp, Dept Virol, Essen, Germany. [Berlin, Aaron M.; Birren, Bruce W.; Henn, Matthew R.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Berlin, Aaron M.; Birren, Bruce W.; Henn, Matthew R.] Harvard Univ, Cambridge, MA 02138 USA. [Lee, Bongshin; Hecker-man, David; Carlson, Jonathan] Microsoft Res, Redmond, WA USA. [Rosen, Hugo R.] Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, Denver, CO USA. [Bihl, Florian K.] Univ Hosp Geneva, Dept Gastroenterol & Hepatol, Geneva, Switzerland. [Cerny, Andreas] Clin Moncucco, Lugano, Switzerland. [Spengler, Ulrich] Bonn Univ Hosp, Dept Internal Med 1, Bonn, Germany. [Liu, Zhimin; Xing, Yanming; Modey, Margret A.; Mar-ion, Tony N.] Univ Tennessee, Ctr Hlth Sci, Hepatitis Cooperat C, Memphis, TN 38163 USA. [Edlin, Brian R.; Talal, Andrew] Weill Cornell Med Coll, Ctr Study Hepatitis C, New York, NY USA. [Daar, Eric S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles Biomed Res Inst, Harbor UCLA Med Ctr, Los Angeles, CA 90095 USA. [Gomperts, Edward D.] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA. [Donfield, Sharyne M.] Rho Inc, Dept Biostat, Chapel Hill, NC USA. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 266 BP 429A EP 430A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400263 ER PT J AU Delgado-Borrego, A Jordan, SH Negre, B Healey, D Lin, WY Ludwig, DA Lok, ASF Everhart, JE Chung, RT AF Delgado-Borrego, Aymin Jordan, Sergio H. Negre, Betania Healey, David Lin, Wenyu Ludwig, David A. Lok, Anna S. F. Everhart, James E. Chung, Raymond T. TI REDUCTION OF INSULIN RESISTANCE WITH EFFECTIVE CLEARANCE OF HEPATITIS C INFECTION: RESULTS FROM THE HALT-C TRIAL SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Delgado-Borrego, Aymin; Jordan, Sergio H.; Negre, Betania; Ludwig, David A.] Univ Miami, Miami, FL USA. [Healey, David; Lin, Wenyu; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Lok, Anna S. F.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. [Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RI Lok, Anna /B-8292-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 271 BP 433A EP 433A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400268 ER PT J AU Morishima, C Shiffman, ML Lindsay, K Szabo, G Dienstag, JL Wright, EC AF Morishima, Chihiro Shiffman, Mitchell L. Lindsay, Karen Szabo, Gyongyi Dienstag, Jules L. Wright, Elizabeth C. TI REDUCED HEPATIC INFLAMMATION IS RELATED TO HCV RNA SUPPRESSION AND CORRELATES WITH LESS FIBROSIS PROGRESSION AND FEWER CIRRHOSIS COMPLICATIONS IN THE HEPATITIS C ANTIVIRAL LONG-TERM TREATMENT AGAINST CIRRHOSIS (HALT-C) TRIAL SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. [Shiffman, Mitchell L.] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA. [Lindsay, Karen] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [Szabo, Gyongyi] Univ Massachusetts, Sch Med, Dept Med, Hepatol & Liver Ctr,Div Gastroenterol, Worcester, MA USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Wright, Elizabeth C.] NIDDKD, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 273 BP 434A EP 434A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400270 ER PT J AU Yogi, H Suganumo, K Parekkadan, B Soto-Gutierrez, A Kitagawa, Y Kitajima, M Toner, M Tompkins, RG Berthiaume, F Tilles, AW Yarmush, ML AF Yogi, Hiroshi Suganumo, Kazuhiro Parekkadan, Biju Soto-Gutierrez, Alejandro Kitagawa, Yuko Kitajima, Masaki Toner, Mehmet Tompkins, Ronald G. Berthiaume, Francois Tilles, Arno W. Yarmush, Martin L. TI THERAPEUTIC POTENTIAL OF HUMAN BONE MARROW-DERIVED STEM CELL BASED LIVER-ASSIST DEVICE FOR FULMINANT HEPATIC FAILURE SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Yogi, Hiroshi; Parekkadan, Biju; Soto-Gutierrez, Alejandro; Toner, Mehmet; Tompkins, Ronald G.; Berthiaume, Francois; Tilles, Arno W.; Yarmush, Martin L.] Massachusetts Gen Hosp, Charlestown, MA USA. [Yogi, Hiroshi; Soto-Gutierrez, Alejandro; Toner, Mehmet; Tompkins, Ronald G.; Berthiaume, Francois; Tilles, Arno W.; Yarmush, Martin L.] Harvard Univ, Sch Med, Boston, MA USA. [Suganumo, Kazuhiro; Kitagawa, Yuko] Keio Univ, Sch Med, Tokyo, Japan. [Kitajima, Masaki] Int Univ Hlth & Welf, Tokyo, Japan. [Parekkadan, Biju] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 288 BP 440A EP 441A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400285 ER PT J AU Goessling, W Babu, R North, TE Lord, AM Wishnok, JS Tannenbaum, SR Zon, LI AF Goessling, Wolfram Babu, Ramesh North, Trista E. Lord, Allegra M. Wishnok, John S. Tannenbaum, Steven R. Zon, Leonard I. TI A ZEBRAFISH MODEL OF ACETAMINOPHEN LIVER TOXICITY REVEALS DIFFERENTIAL RESPONSE PATTERNS OF THE SERUM PROTEOME AND HEPATIC GENE EXPRESSION SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Goessling, Wolfram; North, Trista E.; Lord, Allegra M.; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Goessling, Wolfram] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Babu, Ramesh; Wishnok, John S.; Tannenbaum, Steven R.] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 352 BP 467A EP 468A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400347 ER PT J AU Mueller, T Pratt, DS Shibolet, O Pascher, A Neuhaus, P Schott, E Wiedenmann, B Berg, T Podolsky, DK AF Mueller, Tobias Pratt, Daniel S. Shibolet, Oren Pascher, Andreas Neuhaus, Peter Schott, Eckart Wiedenmann, Bertram Berg, Thomas Podolsky, Daniel K. TI BILIARY EPITHELIAL CELLS IN HUMAN END-STAGE CHRONIC INFLAMMATORY LIVER DISEASE EXHIBIT ENHANCED TLR- AND NOD PROTEIN-MEDIATED INNATE IMMUNE RESPONSES SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Mueller, Tobias; Schott, Eckart; Wiedenmann, Bertram; Berg, Thomas] Charite Univ Med Berlin, Med Klin Schwerpunkt Gastroenterol & Hepatol, Campus Virchow Klinikum, D-13353 Berlin, Germany. [Pascher, Andreas; Neuhaus, Peter] Charite Univ Med Berlin, Klin Allgemein Visceral & Transplantat Chirurg, Campus Virchow Klinikum, D-13353 Berlin, Germany. [Mueller, Tobias; Pratt, Daniel S.; Shibolet, Oren; Podolsky, Daniel K.] Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 677 BP 609A EP 609A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757401064 ER PT J AU Bleibel, W Hussain, G Lai, M Hayne, C Afdhal, NH Lou, D AF Bleibel, Wissam Hussain, Ghazi Lai, Michelle Hayne, Cynthia Afdhal, Nezam H. Lou, Daryl TI HIGH PREVALENCE OF HEPATIC STEATOSIS AND ITS IMPACT ON FIBROSIS IN CHRONIC HEPATITIS B SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Bleibel, Wissam; Hussain, Ghazi; Lai, Michelle; Hayne, Cynthia; Afdhal, Nezam H.; Lou, Daryl] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 831 BP 677A EP 678A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757401215 ER PT J AU Nahmias, Y Goldwasser, J Yormush, ML Chung, RT AF Nahmias, Yaakov Goldwasser, Jonathan Yormush, Martin L. Chung, Raymond T. TI LONG TERM APOB-DEPENDENT HCV SECRETION IS BLOCKED BY THE GRAPEFRUIT FLAVONOID NARIN-GENIN SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Nahmias, Yaakov; Goldwasser, Jonathan; Yormush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Charlestown, MA USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Nahmias, Yaakov/H-4725-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 1012 BP 760A EP 761A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757401395 ER PT J AU Shao, RX Lin, WY Peng, LF Sabharwal, S Chung, WJ Chung, RT AF Shao, Run-Xuan Lin, Wenyu Peng, Lee F. Sabharwal, Sabina Chung, Woo Jin Chung, Raymond T. TI THE IFN ANTAGONIST SOCS3 DOWNREGULATES HEPATITIS C VIRUS REPLICATION IN CELL CULTURE SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Shao, Run-Xuan; Lin, Wenyu; Peng, Lee F.; Sabharwal, Sabina; Chung, Woo Jin; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 1026 BP 766A EP 766A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757401409 ER PT J AU Lin, WY Shao, RX Peng, LF Sabharwal, S Chung, WJ Chung, RT AF Lin, Wenyu Shao, Run-Xuan Peng, Lee F. Sabharwal, Sabina Chung, Woo Jin Chung, Raymond T. TI EVIDENCE FOR BOTH DIRECT AND INDIRECT REGULATION OF HCV REPLICATION BY TGF-beta 1 SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Lin, Wenyu; Shao, Run-Xuan; Peng, Lee F.; Sabharwal, Sabina; Chung, Woo Jin; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 1056 BP 778A EP 779A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757401439 ER PT J AU Speliotes, EK Massaro, JM Hoffmann, U Ramachandran, VS Sahani, DV Hirschhorn, JN O'Donnell, CJ Fox, CS AF Speliotes, Elizabeth K. Massaro, Joseph M. Hoffmann, Udo Ramachandran, Vasan S. Sahani, Dushyant V. Hirschhorn, Joel N. O'Donnell, Christopher J. Fox, Caroline S. TI FATTY LIVER SPECIFICALLY ASSOCIATES WITH ABNORMALITIES IN LIND AND GLUCOSE METABOLISM: THE FRAMINGHAM HEART STUDY SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Speliotes, Elizabeth K.; Hoffmann, Udo; Sahani, Dushyant V.; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirschhorn, Joel N.] Broad Inst, Cambridge, MA USA. [Speliotes, Elizabeth K.; Massaro, Joseph M.; Hoffmann, Udo; Ramachandran, Vasan S.; O'Donnell, Christopher J.; Fox, Caroline S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Ramachandran, Vasan S.] Boston Univ, Med Ctr, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 1143 BP 817A EP 817A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757401524 ER PT J AU Birch, CE Kim, AY Reyor, LL Bowen, MJ Nagami, EH McGovern, B AF Birch, Christopher E. Kim, Arthur Y. Reyor, Laura L. Bowen, Melinda J. Nagami, Ellen H. McGovern, Barbara TI RAPID VIROLOGIC RESPONSE IS COMMON IN ACUTE HEPATITIS C VIRUS (HCV) INFECTION REGARDLESS OF GENOTYPE SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Birch, Christopher E.; Kim, Arthur Y.; Reyor, Laura L.; Bowen, Melinda J.; Nagami, Ellen H.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kim, Arthur Y.] Harvard Univ, Sch Med, Boston, MA USA. [Birch, Christopher E.; Nagami, Ellen H.] Harvard Ctr AIDS Res, Boston, MA USA. [McGovern, Barbara] Lemuel Shattuck Hosp, Jamaica Plain, MA USA. [McGovern, Barbara] Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 1233 BP 857A EP 857A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757401613 ER PT J AU Shiffman, ML Hamzeh, FM Chung, RT AF Shiffman, Mitchell L. Hamzeh, Fayez M. Chung, Raymond T. TI EFFECT OF TIME TO RESPONSE ON VIRAL BREAKTHROUGH AND RELAPSE RATES IN PATIENTS INFECTED WITH HCV GENOTYPE 1 AND TREATED WITH PEGINTERFERON ALFA-2A PLUS RIBAVIRIN SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Shiffman, Mitchell L.] VCU Med Ctr, Richmond, VA USA. [Hamzeh, Fayez M.] Roche, Nutley, NJ USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 1243 BP 862A EP 862A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757401622 ER PT J AU Lo Re, V Amorosa, V Localio, AR O'Flynn, RM Teal, V Dorey-Stein, Z Kostman, J Gross, R AF Lo Re, Vincent Amorosa, Valerianna Localio, A. Russell O'Flynn, Rose M. Teal, Valerie Dorey-Stein, Zachariah Kostman, Jay Gross, Robert TI DIFFERENCES IN ADHERENCE TO PEG-INTERFERON AND RIBAVIRIN AMONG SUBGROUPS PERCEIVED TO BE AT-RISK FOR NON-ADHERENCE SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Lo Re, Vincent; Amorosa, Valerianna; Dorey-Stein, Zachariah; Kostman, Jay; Gross, Robert] Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Localio, A. Russell; Teal, Valerie] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Localio, A. Russell; Teal, Valerie] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Lo Re, Vincent; Localio, A. Russell; Gross, Robert] Univ Penn, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. [Amorosa, Valerianna; O'Flynn, Rose M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RI Lo Re, Vincent/N-7817-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 1317 BP 896A EP 897A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757401696 ER PT J AU Lai, KK Lohia, N Booth, GC Shang, SF Campbell, JS Beretta, L AF Lai, Keane K. Lohia, Neha Booth, Garrett C. Shang, Sufen Campbell, Jean S. Beretta, Laura TI PROTEOME CHANGES ASSOCIATED WITH DISEASE PROGRESSION IN THE PDGF-C TRANSGENIC MOUSE MODEL OF HEPATIC FIBROSIS AND HEPATOCELLULAR CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Lohia, Neha; Booth, Garrett C.; Shang, Sufen; Beretta, Laura] Fred Hutchinson Canc Res Ctr, Mol Diagnost Program, Seattle, WA 98104 USA. [Lai, Keane K.] Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. [Campbell, Jean S.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Lai, Keane K.] Fred Hutchinson Canc Res Ctr, Mol Diagnost Program, Div Gastroenterol, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 1502 BP 974A EP 975A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757402174 ER PT J AU Xu, YH Li, H Gao, RL Kaplan, DE AF Xu, Yanhui Li, Hong Gao, Rui Lin Kaplan, David E. TI SUPPRESSED TUMOR ANTIGEN SPECIFIC T-CELL RESPONSES IN HUMAN HEPATOCELLULAR CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Gao, Rui Lin; Kaplan, David E.] Res Philadelphia VA Med Ctr, Philadelphia, PA USA. [Xu, Yanhui; Li, Hong; Kaplan, David E.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 1523 BP 984A EP 984A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757402194 ER PT J AU Lok, ASF Everhart, JE Chung, RT Kim, HY Everson, GT Hoefs, JC Greenson, JKK AF Lok, Anna S. F. Everhart, James E. Chung, Raymond T. Kim, Hae-Young Everson, Gregory T. Hoefs, John C. Greenson, Joel K. K. TI HEPATIC STEATOSIS DECREASES WITH ADVANCING HEPATIC FIBROSIS: FINDINGS FROM THE HEPATITIS C ANTIVIRAL LONG-TERM TREATMENT AGAINST CIRRHOSIS TRIAL (HALT-C) SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Lok, Anna S. F.] Univ Michigan, Ctr Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Everhart, James E.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Kim, Hae-Young] New England Res Inst, Watertown, MA 02172 USA. [Everson, Gregory T.] Univ Colorado, Denver, CO 80202 USA. [Hoefs, John C.] Univ Calif Irvine, Irvine, CA USA. [Greenson, Joel K. K.] Univ Michigan, Ann Arbor, MI 48109 USA. RI Lok, Anna /B-8292-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 1777 BP 1101A EP 1101A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757402455 ER PT J AU Peng, LF Kim, S Matchacheep, S Maloof, N Lin, WY Beeler, A Porco, JA Schreiber, S Chung, RT AF Peng, Lee F. Kim, SunSuk Matchacheep, Sirinya Maloof, Nicole Lin, Wenyu Beeler, Aaron Porco, John A. Schreiber, Stuart Chung, Raymond T. TI DISCOVERY, DESIGN, AND CHARACTERIZATION OF MODULATORS OF HCV REPLICATION SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Peng, Lee F.; Kim, SunSuk; Lin, Wenyu; Chung, Raymond T.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. [Peng, Lee F.; Matchacheep, Sirinya; Maloof, Nicole; Schreiber, Stuart] Harvard Univ, Cambridge, MA 02138 USA. [Beeler, Aaron; Porco, John A.] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2008 VL 48 IS 4 SU S MA 1889 BP 1155A EP 1155A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757402565 ER PT J AU Koreishi, A Mandal, R Nazarian, R Saenz, A Klepeis, V McDonald, A AF Koreishi, A. Mandal, R. Nazarian, R. Saenz, A. Klepeis, V. McDonald, A. TI Nephrogenic systemic fibrosis: an autopsy case series SO HISTOPATHOLOGY LA English DT Meeting Abstract CT 27th International Congress of the International-Academy-of-Pathology CY OCT 12-17, 2008 CL Athens, GREECE SP Int Acad Pathol C1 [Koreishi, A.; Mandal, R.; Nazarian, R.; Saenz, A.; Klepeis, V.; McDonald, A.] Massachusetts Gen Hosp, 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 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD OCT PY 2008 VL 53 MA 012 BP 6 EP 6 PG 1 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 352VF UT WOS:000259524800013 ER PT J AU Farris, AB Deshpande, V Ganguly, A Lauwers, G AF Farris, A. B. Deshpande, V. Ganguly, A. Lauwers, G. TI Autoimmune pancreatitis-related diabetes: quantitative analysis of endocrine and islet inflammatory cells SO HISTOPATHOLOGY LA English DT Meeting Abstract CT 27th International Congress of the International-Academy-of-Pathology CY OCT 12-17, 2008 CL Athens, GREECE SP Int Acad Pathol C1 [Farris, A. B.; Deshpande, V.; Ganguly, A.; Lauwers, G.] Massachusetts Gen Hosp, Dept Pathol Serv, 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 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD OCT PY 2008 VL 53 MA 305 BP 134 EP 134 PG 1 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 352VF UT WOS:000259524800306 ER PT J AU Hsu, M Misdraji, J AF Hsu, M. Misdraji, J. TI Ruptured appendiceal diverticula mimicking low-grade appendiceal mucinous neoplasms with localized pseudomyxoma peritonei SO HISTOPATHOLOGY LA English DT Meeting Abstract CT 27th International Congress of the International-Academy-of-Pathology CY OCT 12-17, 2008 CL Athens, GREECE SP Int Acad Pathol C1 [Hsu, M.; Misdraji, J.] Massachusetts Gen Hosp, Dept Pathol, 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 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD OCT PY 2008 VL 53 MA 314 BP 138 EP 138 PG 1 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 352VF UT WOS:000259524800315 ER PT J AU Younes, M Lauwers, G Ertan, A Verm, R Bridges, M Woods, K Meriano, F Schmulen, C Colman, R McKechnie, J Lechago, J AF Younes, M. Lauwers, G. Ertan, A. Verm, R. Bridges, M. Woods, K. Meriano, F. Schmulen, C. Colman, R. McKechnie, J. Lechago, J. TI The significance of an indefinite for dysplasia diagnosis in patients with barrett metaplasia SO HISTOPATHOLOGY LA English DT Meeting Abstract CT 27th International Congress of the International-Academy-of-Pathology CY OCT 12-17, 2008 CL Athens, GREECE SP Int Acad Pathol C1 Baylor Coll Med, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD OCT PY 2008 VL 53 MA 396 BP 173 EP 173 PG 1 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 352VF UT WOS:000259524800397 ER PT J AU Flavin, R Smyth, P Barrett, C Russell, S Wen, H Wei, J Laios, A OToole, S Ring, M Denning, K Li, J Aherne, S Sammarae, D Aziz, NA Alhadi, A Finn, S Loda, M Sheppard, B Sheils, O OLeary, J AF Flavin, R. Smyth, P. Barrett, C. Russell, S. Wen, H. Wei, J. Laios, A. OToole, S. Ring, M. Denning, K. Li, J. Aherne, S. Sammarae, D. Aziz, N. Abdul Alhadi, A. Finn, S. Loda, M. Sheppard, B. Sheils, O. OLeary, J. TI MIR-29B expression is associated with disease-free survival in ovarian serous carcinoma patients SO HISTOPATHOLOGY LA English DT Meeting Abstract CT 27th International Congress of the International-Academy-of-Pathology CY OCT 12-17, 2008 CL Athens, GREECE SP Int Acad Pathol C1 [Flavin, R.; Smyth, P.; Barrett, C.; Russell, S.; Ring, M.; Denning, K.; Li, J.; Aherne, S.; Finn, S.; Sheils, O.; OLeary, J.] Trinity Coll Dublin, Dept Histopathol, Dublin 2, Ireland. [Wen, H.; Wei, J.] NYU, Dept Pathol, New York, NY 10003 USA. [Laios, A.; OToole, S.; Sammarae, D.; Aziz, N. Abdul; Alhadi, A.; Sheppard, B.] Trinity Coll Dublin, Dept Obstet & Gynecol, Dublin, Ireland. [Loda, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 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 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD OCT PY 2008 VL 53 MA 416 BP 183 EP 183 PG 1 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 352VF UT WOS:000259524800417 ER PT J AU Chanudet, E Ye, H Ferry, J Bacon, C Adam, P Muller-Hermelink, H Radford, J Pileri, S Ichimura, K Collins, P Hamoudi, R Nicholson, A Wotherspoon, A Isaacson, P Du, M AF Chanudet, E. Ye, H. Ferry, J. Bacon, C. Adam, P. Mueller-Hermelink, H. Radford, J. Pileri, S. Ichimura, K. Collins, P. Hamoudi, R. Nicholson, A. Wotherspoon, A. Isaacson, P. Du, M. TI A20 deletion, new insights in translocation negative malt lymphomas SO HISTOPATHOLOGY LA English DT Meeting Abstract CT 27th International Congress of the International-Academy-of-Pathology CY OCT 12-17, 2008 CL Athens, GREECE SP Int Acad Pathol C1 [Chanudet, E.; Ye, H.; Bacon, C.; Ichimura, K.; Collins, P.; Hamoudi, R.; Du, M.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Ferry, J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Adam, P.; Mueller-Hermelink, H.] Univ Wurzburg, Inst Pathol, D-97070 Wurzburg, Germany. [Radford, J.] Christ Hosp, Dept Med Oncol, Manchester, Lancs, England. [Pileri, S.] Univ Bologna, Unita Operativa Emolinfopatol, I-40126 Bologna, Italy. [Nicholson, A.] Royal Brompton Hosp, Dept Histopathol, London SW3 6LY, England. [Wotherspoon, A.] Royal Marsden Hosp, Dept Histopathol, London SW3 6JJ, England. [Isaacson, P.] UCL, Dept Histopathol, London WC1E 6BT, England. RI Radford, John/N-1331-2015; Chanudet, Estelle/N-4064-2015 OI Radford, John/0000-0001-7898-2786; NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD OCT PY 2008 VL 53 MA 512 BP 224 EP 224 PG 1 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 352VF UT WOS:000259524800513 ER PT J AU Farris, A Turbiner, J Wu, S Nichols, J Wu, C AF Farris, A. Turbiner, J. Wu, S. Nichols, J. Wu, C. TI Variability in the gleason grading of poorly formed glands and the prediction of PSA failure from prostatic adenocarcinoma SO HISTOPATHOLOGY LA English DT Meeting Abstract CT 27th International Congress of the International-Academy-of-Pathology CY OCT 12-17, 2008 CL Athens, GREECE SP Int Acad Pathol C1 [Farris, A.; Turbiner, J.; Wu, S.; Nichols, J.; Wu, C.] Massachusetts Gen Hosp, Pathol Serv, 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 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD OCT PY 2008 VL 53 MA 626 BP 273 EP 273 PG 1 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 352VF UT WOS:000259524800627 ER PT J AU Scaria, A Pechan, P Lukason, M Rubin, H DuFresne, E MacLachlan, T Wills, M Flaxel, C Kim, I Kiss, S Miller, J Veres, G Hauswirth, W Wadsworth, S AF Scaria, Abraham Pechan, Peter Lukason, Mike Rubin, Hillard DuFresne, Elizabeth MacLachlan, Tim Wills, Margaret Flaxel, Christina Kim, Ivana Kiss, Szilard Miller, Joan Veres, Gabor Hauswirth, William Wadsworth, Samuel TI An anti-VEGF AAV gene therapy approach for neovascular complications of age-related macular degeneration - efficacy and safety studies in murine and primate models SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 16th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY NOV 13-16, 2008 CL Brugge, BELGIUM SP European Soc Gene & Cell Therapy C1 [Scaria, Abraham; Pechan, Peter; Lukason, Mike; Rubin, Hillard; DuFresne, Elizabeth; MacLachlan, Tim; Wadsworth, Samuel] Genzyme Corp, Gene Therapy, Framingham, MA 01701 USA. [Wills, Margaret] Pharm Tox, Chalk River Labs, Sierra, NV USA. [Flaxel, Christina] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. [Kim, Ivana; Kiss, Szilard; Miller, Joan] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Veres, Gabor] Appl Genet Therapies Corp, Gene Therapy, Alachua, FL USA. [Hauswirth, William] Univ Florida, Gainesville, FL USA. EM sam.wadsworth@genzyme.com NR 0 TC 0 Z9 0 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2008 VL 19 IS 10 BP 1065 EP 1065 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 368PF UT WOS:000260633700024 ER PT J AU Dirice, E Sanlioglu, AD Kahraman, S Omer, A Balci, MK Griffith, TS Sanlioglu, S AF Dirice, Ercument Sanlioglu, Ahter Dilsad Kahraman, Sevim Omer, Abdulkadir Balci, Mustafa Kemal Griffith, Thomas S. Sanlioglu, Salih TI Prolonged normoglycemia in STZ-induced diabetic rats transplanted with Adenovirus-mediated human TRAIL gene (Ad5hTRAIL) infected islets SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 16th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY NOV 13-16, 2008 CL Brugge, BELGIUM SP European Soc Gene & Cell Therapy C1 [Dirice, Ercument; Sanlioglu, Ahter Dilsad; Kahraman, Sevim; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Human Gene Therapy Unit, Dept Med Biol & Genet, TR-07058 Antalya, Turkey. [Omer, Abdulkadir] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. [Balci, Mustafa Kemal] Akdeniz Univ, Fac Med, Div Endocrinol & Metab Dis, TR-07058 Antalya, Turkey. [Griffith, Thomas S.] Univ Iowa, Gene Therapy Ctr, Iowa City, IA USA. [Griffith, Thomas S.] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA. EM dercument@akdeniz.edu.tr RI BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Salih/F-9305-2016 OI BALCI, Mustafa Kemal/0000-0002-6494-3249; NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2008 VL 19 IS 10 BP 1119 EP 1120 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 368PF UT WOS:000260633700169 ER PT J AU Kahraman, S Dirice, E Sanlioglu, AD Balci, MK Omer, A Griffith, T Sanlioglu, S AF Kahraman, Sevim Dirice, Ercument Sanlioglu, Ahter Dilsad Balci, Mustafa Kemal Omer, Abdulkadir Griffith, Thomas Sanlioglu, Salih TI In vivo imaging to detect the duration of adenovirus mediated EGFP transgene expression in allogeneic islet grafts SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 16th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY NOV 13-16, 2008 CL Brugge, BELGIUM SP European Soc Gene & Cell Therapy C1 [Kahraman, Sevim; Dirice, Ercument; Sanlioglu, Ahter Dilsad; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Human Gene Therapy Unit, Dept Med Biol & Genet, TR-07058 Antalya, Turkey. [Balci, Mustafa Kemal] Akdeniz Univ, Fac Med, Div Endocrinol & Metab Dis, TR-07058 Antalya, Turkey. [Omer, Abdulkadir] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. [Griffith, Thomas] Univ Iowa, Coll Med, Dept Urol, Ctr Gene Therapy, Iowa City, IA 52242 USA. EM skahraman@akdeniz.edu.tr RI BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Salih/F-9305-2016 OI BALCI, Mustafa Kemal/0000-0002-6494-3249; NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2008 VL 19 IS 10 BP 1121 EP 1122 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 368PF UT WOS:000260633700174 ER PT J AU Sahin, A Maxfield, S Bullain, S Sanchez, C Baratta, E Carter, BS AF Sahin, Ayguen Maxfield, Steven Bullain, Szofia Sanchez, Carlos Baratta, Elisabeth Carter, Bob S. TI The "3rd generation" chimeric immune receptor engineered T cells: Can we improve adoptive immunotherapy strategies against glioblastoma? SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 16th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY NOV 13-16, 2008 CL Brugge, BELGIUM SP European Soc Gene & Cell Therapy C1 [Sahin, Ayguen; Maxfield, Steven; Bullain, Szofia; Sanchez, Carlos; Baratta, Elisabeth; Carter, Bob S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM bcarter@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2008 VL 19 IS 10 BP 1140 EP 1140 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 368PF UT WOS:000260633700223 ER PT J AU Yeh, IT Lenci, RE Qin, Y Buddavarapu, K Ligon, AH Leteurtre, E Do Cao, C Cardot-Bauters, C Pigny, P Dahia, PLM AF Yeh, I-Tien Lenci, Romina E. Qin, Yuejuan Buddavarapu, Kalyan Ligon, Azra H. Leteurtre, Emmanuelle Do Cao, Christine Cardot-Bauters, Catherine Pigny, Pascal Dahia, Patricia L. M. TI A germline mutation of the KIF1B beta gene on 1p36 in a family with neural and nonneural tumors SO HUMAN GENETICS LA English DT Article ID MARIE-TOOTH-DISEASE; MOLECULAR-GENETICS; HUMAN GLIOBLASTOMA; CANCER; PHEOCHROMOCYTOMA; GENOME; APOPTOSIS; CELLS AB Recently, the KIF1B beta gene on 1p36, a region commonly deleted in neural crest cancers, was found to be a proapoptotic factor for sympathetic precursors. KIF1B beta mutations were detected in pheochromocytomas and neuroblastomas, two sympathetic lineage tumors, suggesting a role for this gene in cancer. Here, we studied five individuals from a three-generation cancer-prone family with a KIF1B beta germline variant and seven of their tumors, both of neural crest and nonneural origin. Genetic studies including sequencing, copy number analysis and fluorescence in situ-hybridization (FISH) showed retention of both KIF1B beta alleles in all neural crest-derived tumors in this family, consistent with haploinsufficiency or methylation of the wild-type allele. In contrast, the lung adenocarcinoma from one mutation carrier had somatic loss of the wild-type allele in agreement with a classical two-hit inactivation. Global transcription analysis of KIF1B beta mutant pheochromocytomas revealed that these tumors are transcriptionally related to pheochromocytomas with RET and NF1 mutations but independent from SDH- and VHL-associated tumors. Furthermore, KIF1B beta-mutant tumors are uniquely enriched for pathways related to glutamate metabolism and the oxidative stress response. Our data start to delineate the signals that are disrupted by KIF1B beta dysfunction in pheochromocytomas and suggest that loss of this gene may also be permissive to the development of nonneural crest malignancies. This may imply the existence of a tissue-specific gene dosage requirement for its tumorigenesis. C1 [Yeh, I-Tien; Dahia, Patricia L. M.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Yeh, I-Tien] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Lenci, Romina E.; Qin, Yuejuan; Buddavarapu, Kalyan; Dahia, Patricia L. M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Dahia, Patricia L. M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Ligon, Azra H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Ligon, Azra H.] Harvard Univ, Sch Med, Boston, MA USA. [Leteurtre, Emmanuelle] CHRU Lille, Lille, France. [Do Cao, Christine; Cardot-Bauters, Catherine] CHRU Lille, Clin Marc Linquette, Serv Endocrinol, Lille, France. [Pigny, Pascal] CHRU Lille, Ctr Biol & Pathol, Lab Biochim & Hormonol, Lille, France. RP Dahia, PLM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, 7703 Floyd Curl Dr,Rm 5053-R3,MC 7880, San Antonio, TX 78229 USA. EM dahia@uthscsa.edu RI Qin, Yuejuan/F-6801-2010 FU Sidney Kimmel Cancer Foundation and the Cancer Therapy and Research Center (CTRC) at the University of Texas Health Science Center at San Antonio [NIH-P30 CA541] FX We thank Ricardo C. Aguiar for insightful comments, William G. Kaelin Jr and Susanne Schlisio for discussions, and Natalie Vena for technical assistance with the FISH analysis. P. L. M. D. is supported by grants from the Sidney Kimmel Cancer Foundation and the Cancer Therapy and Research Center (CTRC) at the University of Texas Health Science Center at San Antonio (NIH-P30 CA541). Authors' contributions: I-T.Y. performed and analyzed experiments and made conceptual contributions, R. L., Y.Q. and K.B., performed experiments, A.H.L. designed experiments and interpreted data; C.D.C. and C.C.B. performed clinical analysis; E.L. and P.P. provided reagents and helped with data interpretation; P.L.M.D. designed experiments, supervised the project and wrote the manuscript. NR 19 TC 74 Z9 75 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 2008 VL 124 IS 3 BP 279 EP 285 DI 10.1007/s00439-008-0553-1 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 358ID UT WOS:000259909500010 PM 18726616 ER PT J AU Targum, SD Busner, J Young, AH AF Targum, Steven D. Busner, Joan Young, Allan H. TI Targeted scoring criteria reduce variance in global impressions SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE scoring criteria; CGI; CNS trials; depressive disorder ID MAJOR DEPRESSIVE DISORDER; COMORBIDITY; SCALE AB Objective This study examined the confounding effect of treatment emergent physical or psychic symptoms on clinical global impression (CGI) ratings in CNS trials and examined the benefit of targeted scoring criteria on clarifying ratings and reducing scoring variance. Methods Twenty-four raters participating in an investigator meeting training session scored a series of scripted CGI scenarios that included treatment emergent symptoms. Results The addition of treatment emergent gastrointestinal (GI) symptoms or anxiety symptoms significantly changed the rating of clinical global improvement and caused a broad CGI-improvement (CGI-I) scoring variance reflecting scoring ambiguity amongst these raters. Re-rating after a presentation of well-defined criteria that addressed these scoring issues narrowed the variance and significantly improved inter-rater reliability. Conclusions It is clear that CNS trials must define scoring criteria for global ratings prior to the initiation of a study to assure ratings consistency. The actual definition of global must be study-specific and may depend upon the targeted symptoms of interest and mechanism of drug action. The targeted criteria that define global must be included in all published reports about the trial. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Targum, Steven D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Targum, Steven D.] BrainCells Inc, San Diego, CA USA. [Busner, Joan] United Biosource Corp, Wayne, PA USA. [Young, Allan H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Targum, SD (reprint author), 222 Berkeley St,Suite 1650, Boston, MA 02116 USA. EM sdtargum@yahoo.com FU BrainCells Inc. (San Diego, California) FX This study was funded in part by BrainCells Inc. (San Diego, California). NR 15 TC 6 Z9 6 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD OCT PY 2008 VL 23 IS 7 BP 629 EP 633 DI 10.1002/hup.966 PG 5 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 360ZW UT WOS:000260098300009 PM 18666094 ER PT J AU Peralta, CA Shlipak, MG AF Peralta, Carmen A. Shlipak, Michael G. TI Hypertension in children with chronic kidney disease - A call to action SO HYPERTENSION LA English DT Editorial Material ID BLOOD-PRESSURE; PROGRESSION; ADOLESCENTS C1 [Peralta, Carmen A.] San Francisco VA Med Ctr, Div Nephrol, San Francisco, CA USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Shlipak, MG (reprint author), VA Med Ctr 111A1, Gen Internal Med Sect, 4150 Clement St, San Francisco, CA 94121 USA. EM Michael.shlipak@ucsf.edu NR 10 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2008 VL 52 IS 4 BP 610 EP 612 DI 10.1161/HYPERTENSIONAHA.108.117242 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 349KF UT WOS:000259279000004 PM 18725582 ER PT J AU Guzik, TJ Czesnikiewicz-Guzik, M Budzyn, K McCann, L Loster, BW Campos, A Harrison, DG AF Guzik, Tomasz J. Czesnikiewicz-Guzik, Marta Budzyn, Klaudia McCann, Louise Loster, Bartlomiej W. Campos-Neto, Antonio Harrison, David G. TI Immune response to Porphyromonas gingivalis antigens plays a role in the pathogenesis of hypertension and vascular dysfunction SO HYPERTENSION LA English DT Meeting Abstract CT 13th Annual Meeting of the European-Council-for-Cardiovascular-Research CY OCT 10-12, 2008 CL Nice, FRANCE C1 [Guzik, Tomasz J.; Budzyn, Klaudia; McCann, Louise; Harrison, David G.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Czesnikiewicz-Guzik, Marta; Loster, Bartlomiej W.] Jagiellonian Univ, Sch Med, Krakow, Poland. [Campos-Neto, Antonio] Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2008 VL 52 IS 4 BP E53 EP E54 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 349KF UT WOS:000259279000256 ER PT J AU Fisher, LE Miller, ME Bailey, SN Davis, JA Anderson, JS Rhode, L Tyler, DJ Triolo, RJ AF Fisher, Lee E. Miller, Michael E. Bailey, Stephanie N. Davis, John A., Jr. Anderson, James S. Rhode, Lori Tyler, Dustin J. Triolo, Ronald J. TI Standing After Spinal Cord Injury With Four-Contact Nerve-Cuff Electrodes for Quadriceps Stimulation SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Functional neuromuscular stimulation; implantable electrodes; paraplegia; rehabilitation ID FUNCTIONAL ELECTRICAL-STIMULATION; RESTORATION; INDIVIDUALS; PATIENT AB This paper describes the performance of a 16-channel implanted neuroprosthesis for standing and transfers after spinal cord injury including four-contact nerve-cuff electrodes stimulating the femoral nerve for knee extension. Responses of the nerve-cuffs were stable and standing times increased by 600% over time-matched values with a similar eight-channel neuroprosthesis utilizing muscle-based electrodes on vastus lateralis for knee extension. C1 [Fisher, Lee E.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Miller, Michael E.; Bailey, Stephanie N.] Vet Affairs Med Ctr, Louis Stokes Cleveland Dept, Cleveland, OH 44106 USA. [Davis, John A., Jr.] Tulane Univ, Med Ctr, Dept Orthopaed, New Orleans, LA 70112 USA. [Anderson, James S.] Case Western Reserve Univ, Dept Surg, Metrohlth Med Ctr, Cleveland, OH 44106 USA. [Rhode, Lori] Univ Hosp, Case Med Ctr, Cleveland, OH 44106 USA. [Tyler, Dustin J.; Triolo, Ronald J.] US Dept Vet Affairs, Rehabil Res & Dev Serv, Cleveland, OH 44106 USA. RP Fisher, LE (reprint author), Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. EM lee.e.fisher@case.edu; mem9@po.cwru.edu; dustin.tyler@case.edu; ronald.triolo@case.edu RI Fisher, Lee/A-3947-2011; Tyler, Dustin/C-7995-2015; OI Tyler, Dustin/0000-0002-2298-8510; Fisher, Lee/0000-0002-9072-3119 FU NCRR NIH HHS [UL1-RR024989, UL1 RR024989]; NIBIB NIH HHS [R01 EB001889-05, 5-R01-EB001889, T32-EB04314-08, R01 EB001889-01, T32 EB004314, R01 EB001889-07, R01 EB001889-02, R01 EB001889-04, R01 EB001889-03, R01 EB001889-06, R01 EB001889] NR 19 TC 28 Z9 28 U1 2 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD OCT PY 2008 VL 16 IS 5 BP 473 EP 478 DI 10.1109/TNSRE.2008.2003390 PG 6 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 373FN UT WOS:000260956500005 PM 18990650 ER PT J AU Buxbaum, LU AF Buxbaum, Laurence U. TI A detrimental role for IgG and FcgammaR in Leishmania mexicana infection SO IMMUNOLOGIC RESEARCH LA English DT Article DE Immunoglobulin G; Protozoan parasite; Leishmania; FcgammaR; IL-10; IL-12; Macrophage; Immune complex ID REGULATORY T-CELLS; WORLD CUTANEOUS LEISHMANIASIS; INNATE IMMUNE-RESPONSE; NITRIC-OXIDE SYNTHASE; GAMMA-RIII CD16; INTERFERON-GAMMA; INTERLEUKIN-10-DEFICIENT MICE; VISCERAL LEISHMANIASIS; DEFICIENT MICE; IN-VIVO AB The intracellular protozoan parasite Leishmania causes leishmaniasis, which is the second biggest killer worldwide among parasitic diseases, after malaria. As drug therapy for leishmaniasis is toxic and resistance is growing, a vaccine is an important weapon against this disease. Unfortunately, no effective vaccine exists for any human parasitic infection. Worse yet, nearly all effective vaccines whose mechanisms are known work through the induction of protective antibodies. Leishmania mexicana causes primarily chronic cutaneous disease. Not only are antibodies not effective at killing Leishmania, as it hides inside the parasitophorous vacuole of the host cell, but new research indicates that IgG antibodies may be crucial in suppressing the host immune response by generating an immunosuppressive interleukin-10 response. IL-10 is able to decrease the needed Th1-generated IFN-gamma and downregulates production of nitric oxide, a required effector mechanism of parasite killing. We have been studying the pathways that the host uses to partially control L. mexicana infection, which include STAT4, IFN-gamma, and inducible nitric oxide synthase, but found that the IL-12 pathway is suppressed by IL-10. We are now studying the mechanisms by which IgG, bound to parasites, can induce IL-10 through Fc gamma R ligation and how this suppresses a healing immune response. We are examining which IgG isotypes bind to which Fc gamma Rs and whether macrophages are the necessary source of IL-10 for chronic disease. Elucidation of these mechanisms may help us to design vaccines that will not induce antibody-mediated immunosuppressive IL-10 responses. C1 [Buxbaum, Laurence U.] Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Buxbaum, Laurence U.] Univ Penn, Sch Med, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. RP Buxbaum, LU (reprint author), Vet Affairs Med Ctr, 3900 Woodland Ave,Res 151, Philadelphia, PA 19104 USA. EM buxbaum@mail.med.upenn.edu FU University of Pennsylvania; NIH [K08-AI01805]; Department of Veterans Affairs FX The work was begun by the author in the lab of Dr. Phillip Scott and continued by Dr. Buxbaum in his own independent lab. We would like to thank Dr. Bolaji Thomas for his in vitro work on macrophages, and Andrea Rosso and Dr. Niansheng Chu for technical help with other aspects of the research. This work was supported by the University of Pennsylvania, by NIH (K08-AI01805), and by a Merit Review Award from the Department of Veterans Affairs. NR 55 TC 14 Z9 14 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD OCT PY 2008 VL 42 IS 1-3 BP 197 EP 209 DI 10.1007/s12026-008-8074-5 PG 13 WC Immunology SC Immunology GA 387KW UT WOS:000261952100017 PM 19002608 ER PT J AU Morandi, A Pandharipande, P Trabucchi, M Rozzini, R Mistraletti, G Trompeo, AC Gregoretti, C Gattinoni, L Ranieri, MV Brochard, L Annane, D Putensen, C Guenther, U Fuentes, P Tobar, E Anzueto, AR Esteban, A Skrobik, Y Salluh, JIF Soares, M Granja, C Stubhaug, A de Rooij, SE Ely, EW AF Morandi, A. Pandharipande, P. Trabucchi, M. Rozzini, R. Mistraletti, G. Trompeo, A. C. Gregoretti, C. Gattinoni, L. Ranieri, M. V. Brochard, L. Annane, D. Putensen, C. Guenther, U. Fuentes, P. Tobar, E. Anzueto, A. R. Esteban, A. Skrobik, Y. Salluh, J. I. F. Soares, M. Granja, C. Stubhaug, A. de Rooij, S. E. Ely, E. Wesley TI Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients SO INTENSIVE CARE MEDICINE LA English DT Editorial Material DE delirium; delirio; delire; delier; delir; delire; confusion; confusione; coma; acute brain dysfunction; psychosis; delirium tremens; Durchgangs-Syndrom; acute verwardheid ID INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED PATIENTS; CONFUSION ASSESSMENT METHOD; SUBSYNDROMAL DELIRIUM; PROGNOSTIC-SIGNIFICANCE; HOSPITAL PATIENTS; MOTORIC SUBTYPES; MEDICAL PATIENTS; SYMPTOMS; OUTCOMES AB Background: Delirium (acute brain dysfunction) is a potentially life threatening disturbance in brain function that frequently occurs in critically ill patients. While this area of brain dysfunction in critical care is rapidly advancing, striking limitations in use of terminology related to delirium internationally are hindering cross-talk and collaborative research. In the English literature, synonyms of delirium such as the Intensive Care Unit syndrome, acute brain dysfunction, acute brain failure, psychosis, confusion, and encephalopathy are widely used. This often leads to scientific "confusion" regarding published data and methodology within studies, which is further exacerbated by organizational, cultural and language barriers. We undertook this multinational effort to identify conflicts in terminology and phenomenology of delirium to facilitate communication across medical disciplines and languages. Methods: The evaluation of the terminology used for acute brain dysfunction was determined conducting communications with 24 authors from academic communities throughout countries/regions that speak the 13 variants of the Romanic languages included into this manuscript. Results: In the 13 languages utilizing Romanic characters, included in this report, we identified the following terms used to define major types of acute brain dysfunction: coma, delirium, delirio, delirium tremens, delire, confusion mentale, delir, delier, Durchgangs-Syndrom, acute verwardheid, intensiv-psykose, IVA-psykos, IVA-syndrom, akutt konfusion/forvirring. Interestingly two terms are very consistent: 100 % of the selected languages use the term coma or koma to describe patients unresponsive to verbal and/or physical stimuli, and 100% use delirium tremens to define delirium due to alcohol withdrawal. Conversely, only 54% use the term delirium to indicate the disorder as defined by the DSM-IV as an acute change in mental status, inattention, disorganized thinking and altered level of consciousness. Conclusions. Attempts towards standardization in terminology, or at least awareness of differences across languages and specialties, will help cross-talk among clinicians and researchers. C1 [Ely, E. Wesley] Vanderbilt Univ Sch Med, Div Allergy Pulm Crit Care Med, Nashville, TN 37203 USA. [Morandi, A.; Ely, E. Wesley] Ctr Hlth Serv Res, Nashville, TN 37232 USA. [Morandi, A.; Rozzini, R.] Poliambulanza Hosp, Dept Internal Med & Geriatr, Brescia, Italy. [Morandi, A.; Trabucchi, M.; Rozzini, R.] Geriatr Res Grp, Brescia, Italy. [Pandharipande, P.] Vanderbilt Univ Sch Med, Dept Anesthesiol, Div Crit Care Med, Nashville, TN USA. [Mistraletti, G.] Univ Milan, Ist Anestesiol & Rianimaz, UO Anestesia & Rianimaz, Azienda Osped San Paolo,Polo Univ, Milan, Italy. [Trompeo, A. C.; Ranieri, M. V.] Univ Turin, Molinette Mauriziano Hosp, Intens Care Unit, Turin, Italy. [Gregoretti, C.] Azienda Osped CTO CRF ICORMA, Intens Care Unit, Turin, Italy. [Gattinoni, L.] Univ Milan, Ist Anestesiol & Rianimaz,Osped Maggiore Policlin, UO Anestesia & Rianimaz,Fdn IRCCS, Dipartimento Anestesia Rianimaz Intens & Subinten, Milan, Italy. [Brochard, L.] Univ Paris 12, Ctr Hosp Albert Chenevier, AP HP, Creteil, France. [Annane, D.] Univ Versailles, Hop Raymond Poincare, AP HP, Serv Reanimat, Garches, France. [Putensen, C.; Guenther, U.] Univ Hosp Sigmund Freud, Dept Anesthesiol & Intens Care Med, Bonn, Germany. [Fuentes, P.] Univ Chile, Clin Hosp, Dept Med, Geriatr Sect, Santiago, Chile. [Anzueto, A. R.] Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Esteban, A.] Hosp Univ Getafe, Intens Care Unit, CIBER Enfermedades Resp, Madrid, Spain. [Skrobik, Y.] Univ Montreal, Hosp Maisonnevue Rosemont, Intens Care Unit, Montreal, PQ, Canada. [Salluh, J. I. F.; Soares, M.] INCA, Inst Nacl Canc, Ctr Tratamento Intens, Intens Care Unit, Rio De Janeiro, Brazil. [Granja, C.] Hosp Pedro Hispano, Med Intens Care Unit, Matosinhos, Portugal. [Stubhaug, A.] Aker Univ Hosp, Rikshosp, Dept Anesthesiol & Intens Care, Oslo, Norway. [de Rooij, S. E.] Univ Amsterdam, Acad Med Ctr, Dept Geriatr, NL-1105 AZ Amsterdam, Netherlands. [Ely, E. Wesley] VA Tennessee Valley Geriatr Res Educ & Clin Ctr, Nashville, TN USA. RP Ely, EW (reprint author), Vanderbilt Univ Sch Med, Div Allergy Pulm Crit Care Med, Nashville, TN 37203 USA. EM wes.ely@vanderbilt.edu RI Salluh, Jorge/F-6779-2012; Soares, Marcio/B-3083-2013; Granja, Cristina/H-8146-2013; Skrobik, Yoanna/K-8165-2014; Tobar, Eduardo/D-4555-2016; FMUP, CINTESIS/C-6631-2014; OI Soares, Marcio/0000-0003-2503-6088; Skrobik, Yoanna/0000-0002-5315-6020; Tobar, Eduardo/0000-0003-2123-6082; FMUP, CINTESIS/0000-0001-7248-2086; Granja, Cristina/0000-0002-5503-051X; Salluh, Jorge/0000-0002-8164-1453 NR 45 TC 49 Z9 61 U1 13 U2 29 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2008 VL 34 IS 10 BP 1907 EP 1915 DI 10.1007/s00134-008-1177-6 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 353LT UT WOS:000259570100026 PM 18563387 ER PT J AU Gans, JS AF Gans, Jerome S. TI The Practice Guidelines: An impressive overview of the state of our art SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Editorial Material ID PSYCHODYNAMIC GROUP-PSYCHOTHERAPY; GROUP-THERAPY; SHAME C1 [Gans, Jerome S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gans, Jerome S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gans, JS (reprint author), 55 Cleveland Rd, Wellesley, MA 02481 USA. EM jsgans@comcast.net NR 13 TC 0 Z9 0 U1 1 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD OCT PY 2008 VL 58 IS 4 SI SI BP 555 EP 566 DI 10.1521/ijgp.2008.58.4.555 PG 12 WC Psychology, Clinical SC Psychology GA 354QX UT WOS:000259655200004 PM 18837664 ER PT J AU McCluggage, WG Young, RH AF McCluggage, W. Glenn Young, Robert H. TI Endometrial stromal sarcomas with true papillae and pseudopapillae SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE uterus; endometrial stromal sarcoma; papillae; pseudopapillae ID SEX-CORD TUMOR; SMOOTH-MUSCLE TUMORS; RHABDOID DIFFERENTIATION; UTERINE; UTERUS; DISTINCTION; PHENOTYPE; NEOPLASMS; FEATURES AB Most endometrial stromal sarcomas (ESSs) have a characteristic histologic appearance and the diagnosis is easily made based on the typical growth pattern, vascular pattern, and cell type. However, there are several variants, which may result in problems in diagnosis and consideration of other neoplasms. We describe 3 examples of a hitherto not well-described phenomenon in uterine ESS, namely the formation of papillae or pseudopapillae. The patients were aged 37, 42, and 52. In 2 cases, the neoplasms were typical ESSs apart from the presence of pseudopapillae; in I case the pseudopapillae were present throughout the neoplasm and in the other this was a focal finding involving 10% of the tuition In the third case, there was a true papillary component involving sex cord-like elements within an ESS and a prominent papillary architecture in the metastatic tumor which developed 7 years later resulted in initial misdiagnosis as a serous adenocarcinoma. This report emphasizes the potential for ESSs to form pseudopapillae or true papillae, which may involve areas of usual ESS or sex cord-like elements. The formation of papillae or pseudopapillae may result in diagnostic difficulty and confusion with other neoplasms, especially if the phenomenon is widespread. C1 [McCluggage, W. Glenn] Royal Grp Hosp Trust, Dept Pathol, Belfast BT12 6BL, Antrim, North Ireland. [Young, Robert H.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP McCluggage, WG (reprint author), Royal Grp Hosp Trust, Dept Pathol, Grosvenor Rd, Belfast BT12 6BL, Antrim, North Ireland. EM glenn.mccluggage@belfasttrust.hscni.net NR 35 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-1691 EI 1538-7151 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 2008 VL 27 IS 4 BP 555 EP 561 DI 10.1097/PGP.0b013e31817a82f9 PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 352QX UT WOS:000259513500014 PM 18753964 ER PT J AU Venditti, EM Bray, GA Carrion-Petersen, ML Delahanty, LM Edelstein, SL Hamman, RF Hoskin, MA Knowler, WC Ma, Y AF Venditti, E. M. Bray, G. A. Carrion-Petersen, M. L. Delahanty, L. M. Edelstein, S. L. Hamman, R. F. Hoskin, M. A. Knowler, W. C. Ma, Y. CA Diabet Prevention Program Res Grp TI First versus repeat treatment with a lifestyle intervention program: attendance and weight loss outcomes SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE behavior modification; metformin; weight loss; maintenance ID MAINTENANCE; PREVENTION; REDUCTION AB Objective: Following unblinding of the Diabetes Prevention Program (DPP) results, a 16-session lifestyle intervention program was offered to all study participants, including those who had initially been randomized to lifestyle treatment. This study compares the effects of the lifestyle program between participants who had previous exposure and those who had not. Design: A 16-session behavioral intervention was conducted in groups at each of the 27 DPP sites during a transitional (bridge) period from the DPP trial to the DPP Outcomes Study (DPPOS). Session participation for this 6-month behavioral weight loss program was confirmed by originally randomized treatment groups. Subjects and measurements: Independently assessed weight measurements were available within a 7-month period before and after the program for 2808 ethnically diverse participants. Results: Participants from the lifestyle group in the DPP were the least likely to attend a repeat offering of a 16-session behavioral weight loss program conducted in groups. Weight loss during the transitional lifestyle program was strongly related to the duration of attendance in the three groups that were participating in the program for the first time (metformin, placebo and troglitazone), but not related to amount of earlier weight loss. Conclusion: Individuals who were naive to the behavioral program lost a greater amount of weight and this was strongly related to their degree of participation. A second exposure to a behavioral weight loss program resulted in unsatisfactory low attendance rates and weight loss. International Journal of Obesity (2008) 32, 1537-1544; doi: 10.1038/ijo.2008.134; published online 19 August 2008 C1 [Venditti, E. M.] Psychiat Inst & Clin, Pittsburgh, PA USA. [Bray, G. A.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Carrion-Petersen, M. L.] Univ Calif San Diego, San Diego, CA 92103 USA. [Delahanty, L. M.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Hamman, R. F.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Hoskin, M. A.; Knowler, W. C.] NIDDK, Phoenix, AZ USA. RP Venditti, EM (reprint author), George Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu RI Uwaifo, Gabriel/M-2361-2016 OI Uwaifo, Gabriel/0000-0002-6962-9304 FU NIH [U01DK] FX Supported by NIH U01DK. NR 13 TC 35 Z9 35 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD OCT PY 2008 VL 32 IS 10 BP 1537 EP 1544 DI 10.1038/ijo.2008.134 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 358PE UT WOS:000259929200012 PM 18711387 ER PT J AU Kozak, KR Moody, JS AF Kozak, Kevin R. Moody, John S. TI The survival impact of the intergroup 0116 trial on patients with gastric cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE adjuvant radiotherapy; stomach neoplasms; SEER program; survival analysis; proportional hazards models ID CHEMOTHERAPY; SURGERY AB Purpose: The Intergroup 0116 (INT 0116) trial demonstrated a survival benefit for a broad group of fully resected gastric cancer patients. This study examined the impact on survival of the release of this landmark trial. Methods and Materials: Patients with gastric carcinoma diagnosed between 1995 and 2004 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Patients from the overall population as well as those potentially eligible for the INT 0116 trial were classified as having been diagnosed either before (19951999) or after (2000-2004) this trial. Both Kaplan-Meier survival analysis and Cox models were used to examine survival trends within these cohorts. Results: For the overall population of 22,982 patients, the use of radiotherapy (RT) significantly changed after the INT 0116 trial (p < 0.0001), with postoperative RT increasing from 6.5% to 13.3%. For the two periods of interest, overall survival significantly improved in recent years (p = 0.00008). A similar improvement was also seen for patients who were potentially eligible for the INT 0116 trial (p = 0.004), with 3-year survival rates improving from 32.2 % to 34.5 %. On both univariate and multivariate analysis, use of RT was associated with a significant survival improvement (HR, 0.65 [0.48-0.88]; p = 0.005). Conclusion: Use of postoperative RT for gastric cancer has significantly increased after the release of the INT 0116 trial, likely reflecting increased use of adjuvant chemoradiotherapy. This change has been associated with improved survival in gastric cancer patients, suggesting that the improved outcome seen in this trial has been successfully translated to the community. (C) 2008 Elsevier Inc. C1 [Moody, John S.] Univ Alabama, Sch Med, Dept Radiat Oncol, Birmingham, AL 35249 USA. [Kozak, Kevin R.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Moody, JS (reprint author), Univ Alabama, Sch Med, Dept Radiat Oncol, 127 Wallace Tumor Inst,619 19th St S, Birmingham, AL 35249 USA. EM jsmoody@uabmc.edu NR 17 TC 24 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2008 VL 72 IS 2 BP 517 EP 521 DI 10.1016/j.ijrobp.2007.12.029 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 350CJ UT WOS:000259329800029 PM 18249500 ER PT J AU de Bruin, DM Burnes, DL Loewenstein, J Chen, YL Chang, S Chen, TC Esmaili, DD de Boer, JF AF de Bruin, Daniel M. Burnes, Daina L. Loewenstein, John Chen, Yueli Chang, Susie Chen, Teresa C. Esmaili, Daniel D. de Boer, Johannes F. TI In vivo three-dimensional imaging of neovascular age-related macular degeneration using optical frequency domain imaging at 1050 nm SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 06-10, 2007 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID COHERENCE TOMOGRAPHY; HIGH-SPEED; ULTRAHIGH-RESOLUTION; CHOROIDAL NEOVASCULARIZATION; HUMAN RETINA; SWEPT-SOURCE; THICKNESS; NERVE; FIBER AB PURPOSE. To assess the application of optical frequency domain imaging (OFDI) at 1050 nm for the detection of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) and its response to treatment. Three patients presenting with blurred vision and exudative AMD were imaged before and after anti-VEGF treatment with ranibizumab. METHODS. The patients were imaged with OFDI, a swept-source-based, high-speed optical coherence tomography (OCT) system developed at the Wellman Center for Photomedicine. A center wavelength of 1050 nm was used that has been demonstrated to provide better imaging of the deeper structures of the retina below the RPE, such as the choroidal vasculature. Three-dimensional data sets were acquired in 2 to 4 seconds. RESULTS. En face images were compiled from cross-sectional OFDI data and correlated with color fundus photography (CF) and fluorescein angiograms (FAs). Cross-sectional images were coregistered with CF and FA to obtain depth-resolved information about CNV, CNV volume, retinal thickness, subretinal fluid volume and height of neurosensory detachment before and after treatment with ranibizumab. A band of reduced reflectivity below the RPE was identified in all three subjects that corresponded to areas of confirmed and suspected occult CNV on FA. After treatment, this band was reduced in volume in all patients. CONCLUSIONS. High-speed 3-D OFDI at 1050 nm is a promising technology for imaging the retina and choroid in neovascular AMD. The developed system at 1050 nm provides good contrast for occult (type 1) CNV and may have advantages compared with time domain and current state of the art spectral domain OCT systems (SD-OCT) at 850 nm. C1 [de Bruin, Daniel M.; Burnes, Daina L.; Chen, Yueli; de Boer, Johannes F.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [de Bruin, Daniel M.; Burnes, Daina L.; Loewenstein, John; Chen, Yueli; Chang, Susie; Chen, Teresa C.; Esmaili, Daniel D.; de Boer, Johannes F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Loewenstein, John; Chang, Susie; Chen, Teresa C.; Esmaili, Daniel D.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP de Boer, JF (reprint author), Vrije Univ Amsterdam, Deboelelaan 1081,FEW T0-67, NL-1081 HV Amsterdam, Netherlands. EM jfdeboer@few.vu.nl RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCRR NIH HHS [R01 RR019768]; NEI NIH HHS [R01 EY014975] NR 40 TC 64 Z9 66 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2008 VL 49 IS 10 BP 4545 EP 4552 DI 10.1167/iovs.07-1553 PG 8 WC Ophthalmology SC Ophthalmology GA 355IZ UT WOS:000259703900046 PM 18390638 ER PT J AU Sandberg, MA Brockhurst, RJ Gaudio, AR Berson, EL AF Sandberg, Michael A. Brockhurst, Robert J. Gaudio, Alexander R. Berson, Eliot L. TI Visual acuity is related to parafoveal retinal thickness in patients with retinitis pigmentosa and macular cysts SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; EDEMA; TRIAL AB PURPOSE. To quantify the prevalence and effect on visual acuity of macular cysts in a large cohort of patients with retinitis pigmentosa. METHODS. In 316 patients with typical forms of retinitis pigmentosa, visual acuity was measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, macular cysts were detected with optical coherence tomography (OCT), and retinal thicknesses was quantified by OCT. The FREQ, LOGISTIC, and GENMOD procedures of SAS (SAS Institute, Cary, NC) were used to evaluate possible risk factors for cyst prevalence, and the MIXED procedure was used to quantify the relationships of visual acuity to retinal thickness measured at different locations within the macula. RESULTS. Macular cysts were found in 28% of the patients, 40% of whom had cysts in only one eye. Macular cysts were seen most often in patients with dominant disease and not at all in patients with X-linked disease (P = 0.006). In eyes with macular cysts, multiple regression analysis revealed that visual acuity was inversely and independently related to retinal thickness at the foveal center (P = 0.038) and within a parafoveal ring spanning an eccentricity of 5 to 10 from the foveal center (P = 0.004). CONCLUSIONS. Macular cysts are a common occurrence in retinitis pigmentosa, especially among patients with dominantly inherited disease. Visual acuity is influenced by edema in the parafovea, as well as in the fovea. C1 [Sandberg, Michael A.; Brockhurst, Robert J.; Gaudio, Alexander R.; Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Sandberg, MA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM masandberg@aol.com FU National Eye Institute [EY00169]; The Foundation Fighting Blindness, Owings Mills, MD FX Supported by National Eye Institute Grant EY00169 and The Foundation Fighting Blindness, Owings Mills, MD. NR 15 TC 23 Z9 24 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2008 VL 49 IS 10 BP 4568 EP 4572 DI 10.1167/iovs.08-1992 PG 5 WC Ophthalmology SC Ophthalmology GA 355IZ UT WOS:000259703900049 PM 18552390 ER PT J AU John, MC Wessely, R Kastrati, A Schomig, A Joner, M Uchihashi, M Crimins, J Lajoie, S Kolodgie, FD Gold, HK Virmani, R Finn, AV AF John, Michael C. Wessely, Rainer Kastrati, Adnan Schoemig, Albert Joner, Michael Uchihashi, Mayu Crimins, Johanna Lajoie, Scott Kolodgie, Frank D. Gold, Herman K. Virmani, Renu Finn, Aloke V. TI Differential Healing Responses in Polymer- and Nonpolymer-Based Sirolimus-Eluting Stents SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE stents; endothelium; polymer AB Objectives We compared the healing and inflammatory responses of polymer-free bare-metal stents (BMS), polymer-free sirolimus-eluting stents (SES) and polymer-free sirolimus-eluting stents plus estradiol (SES+ED) to Cypher drug-eluting stents (CDES) in a rabbit model of overlapping stent placement. Background Inflammatory responses to polymers and delayed healing remain important safety issues associated with CDES. Whether nonpolymeric stents that elute sirolimus or sirolimus and estradiol provoke less inflammation and heal better is unknown. Methods Twenty-eight rabbits received 2 overlapping stents in each iliac artery: SES, SES+ED, BMS, or CDES, and vessels were harvested at 28 days for histology and scanning electron microscopy. Results Although similar at nonoverlapping segments, neointimal thickness within the overlap site of CDES was significantly less than in SES, SES+ED, and BMS (0.07 +/- 0.04 mm vs. 0.16 +/- 0.03 mm, 0.14 +/- 0.03 mm, and 0.15 +/- 0.03 mm, p < 0.0001). Endothelialization was greater in SES, SES+ED, and BMS compared with CDES in nonoverlapping sections (80.0 +/- 5.0% vs. 95.3 +/- 5.0%, 97.5 +/- 2.5%, and 96.7 +/- 3.8%; p = 0.0028) and overlapping sections (85.8 +/- 2.9% vs. 90.8 +/- 6.3%, 89.2 +/- 6.3%, and 48.3 +/- 2.9%; p < 0.0001). The number of luminal eosinophils was also less in overlapping sections of SES, SES+ED, and BMS versus CDES but was similar in nonoverlapping sections. Conclusions Polymer-free stents coated with SES or SES+ED result in less robust neointimal suppression but markedly improved arterial healing compared with CDES in the rabbit model. (J Am Coll Cardiol Intv 2008;1:535-44) (C) 2008 by the American College of Cardiology Foundation C1 [John, Michael C.; Uchihashi, Mayu; Crimins, Johanna; Lajoie, Scott; Gold, Herman K.; Finn, Aloke V.] Massachusetts Gen Hosp, Dept Internal Med, Cardiac Unit, Boston, MA 02114 USA. [Joner, Michael; Kolodgie, Frank D.; Virmani, Renu] Int Registry Pathol, CVPath, Gaithersburg, MD USA. [Wessely, Rainer; Kastrati, Adnan; Schoemig, Albert] Tech Univ Munich, Med Klin Rechts Isar, Munich, Germany. [Wessely, Rainer; Kastrati, Adnan; Schoemig, Albert] Tech Univ Munich, Deutsch Herzzentrum, Munich, Germany. RP Finn, AV (reprint author), Emory Univ, Dept Internal Med, Sch Med, Emory Crawford Long Hosp, 550 Peachtree St NE, Atlanta, GA 30308 USA. EM avfinn@emory.edu FU CVPath Institute, Inc., a nonprofit institute in Gaithersburg, Maryland; Bavarian Research Foundation, Munich, Germany; Medtronic AVE; Guidant; Abbott; W.L. Gore; Atrium Medical Corporation; Boston Scientific; NDC Cordis Corporation; Novartis; Orbus Medical Technologies; Biotronik; BioSensors; Alchimer; Terumo FX This study was supported, in part, by a grant from CVPath Institute, Inc., a nonprofit institute in Gaithersburg, Maryland, and by the Bavarian Research Foundation, Munich, Germany. Stents were provided by Translumina, Hechingen, Germany. Dr. Virmani receives company-sponsored research support from Medtronic AVE, Guidant, Abbott, W.L. Gore, Atrium Medical Corporation, Boston Scientific, NDC Cordis Corporation, Novartis, Orbus Medical Technologies, Biotronik, BioSensors, Alchimer, and Terumo. Dr. Vrimani is also a consultant to Medtronic AVE, Guidant, Abbott Laboratories, W. L. Gore, Terumo, and Volcano Therapeutics, Inc. The abstract was presented at the American Heart Association Scientific Sessions, November 12-16, 2006, Chicago, Illinois. NR 27 TC 33 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD OCT PY 2008 VL 1 IS 5 BP 535 EP 544 DI 10.1016/j.jcin.2008.08.004 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V12FY UT WOS:000207586300012 PM 19463356 ER PT J AU Frankenberger, R Taschner, M Garcia-Godoy, F Petschelt, A Kramer, N AF Frankenberger, Roland Taschner, Michael Garcia-Godoy, Franklin Petschelt, Anselm Kraemer, Norbert TI Leucite-reinforced Glass Ceramic Inlays and Onlays after 12 Years SO JOURNAL OF ADHESIVE DENTISTRY LA English DT Article DE ceramics; resin composites; luting; dual-curing; dentin bonding; clinical trial ID CLINICAL-PERFORMANCE; RESIN COMPOSITE; DENTIN; RESTORATIONS; ADHESIVES; QUALITY; 4-YEAR; ETCH AB Purpose: This controlled clinical trial aimed to evaluate IPS Empress inlays and onlays over 12 years. The null hypothesis was that different luting resins would have no influence on clinical outcome. Materials and Methods: In the course of a prospective clinical long-term trial, 96 ceramic inlays and onlays were placed in 34 patients using one adhesive (Syntac) and four different luting composites Tetric, Variolink Low, Variolink Ultra, Dual Cement). Recalls were carried out by two calibrated investigators using modified USPHS codes and criteria at baseline, 1, 2, 4, 6, 8, and 12 years. Results: Fifteen of the 96 restorations had to be replaced (failure rate 16%; Kaplan-Meier); 12 of them suffered bulk fractures. After twelve years of clinical service, significantly more bulk fractures were found when light-curing composite was used for luting (p < 0.05). Fractures were noticed between 3 and 4 years of clinical service and later after 11 to 12 years; aside from those times, no single fracture occurred. Secondary caries was not observed. Conclusion: IPS Empress inlays and onlays exhibited satisfactory clinical outcomes over a 12-year clinical period. Restorations luted with dual-cured resin composites revealed significantly fewer bulk fractures. C1 [Frankenberger, Roland; Taschner, Michael; Petschelt, Anselm] Univ Erlangen Nurnberg, Univ Med Ctr, Dent Clin Operat Dent & Periodontol 1, D-91054 Erlangen, Germany. [Garcia-Godoy, Franklin] Coll Dent Med, Biosci Res Ctr, Ft Lauderdale, FL USA. [Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA. [Kraemer, Norbert] Tech Univ Dresden, Univ Med Ctr Carl Gustav Carus, Dept Pediat Dent, Dresden, Germany. RP Frankenberger, R (reprint author), Univ Erlangen Nurnberg, Univ Med Ctr, Dent Clin Operat Dent & Periodontol 1, Gluckstr 11, D-91054 Erlangen, Germany. EM frankbg@dent.uni-erlangen.de NR 29 TC 53 Z9 55 U1 0 U2 6 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 1461-5185 J9 J ADHES DENT JI J. Adhes. Dent. PD OCT PY 2008 VL 10 IS 5 BP 393 EP 398 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 362MJ UT WOS:000260201500012 PM 19058686 ER PT J AU Griffith, JM Hasley, JP Liu, H Severn, DG Conner, LH Adler, LE AF Griffith, Jay M. Hasley, Joseph P. Liu, Hong Severn, Daniel G. Conner, Latoya H. Adler, Lawrence E. TI Qigong Stress Reduction in Hospital Staff SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; TAI-CHI; ESSENTIAL-HYPERTENSION; PERCEIVED STRESS; BLOOD-PRESSURE; EXERCISE; ANXIETY; HEALTH; MANAGEMENT; DISORDERS AB Objective: The aim of this study was to investigate the effectiveness of a qigong training program in reducing stress in hospital staff. Methods: Subjects were randomly assigned to a 6-week intervention of either qigong practice (n = 16) or a waiting list (n = 21). The primary measure of stress was the Perceived Stress Scale. Secondary measures included the Short Form 36 (SF-36) quality-of-life measure and a 100-mm analog pain scale. Results: The qigong group demonstrated a statistically significant reduction of perceived stress compared to the control group (p = 0.02). On the Social Interaction subscale of the SF-36, the qigong group demonstrated greater improvement compared to controls (p = 0.04). Within-groups analyses demonstrated that the qigong group (p = 0.03), but not the control group, experienced a significant reduction of pain intensity. A regression analysis demonstrated an association between higher baseline stress levels and greater improvement within the qigong group (R-2 = 0.34; p = 0.02). Conclusions: These results suggest that short-term exposure to qigong was effective in reducing stress in hospital staff. Further studies are needed to evaluate the possible effectiveness of qigong in reducing pain and in improving quality of life. C1 [Griffith, Jay M.; Adler, Lawrence E.] VISN 19 MIRECC, Dept Psychiat, Denver, CO USA. [Griffith, Jay M.; Severn, Daniel G.; Adler, Lawrence E.] Univ Colorado, Denver Sch Med, Denver, CO 80202 USA. [Hasley, Joseph P.; Conner, Latoya H.] Denver Vet Affairs Med Ctr, VISN MIRECC 19, Denver, CO USA. [Liu, Hong] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Griffith, JM (reprint author), 7904 E 9th Ave, Denver, CO 80230 USA. EM jaymgriffithmd@aol.com FU Department of Veterans Affairs VISN 19 MIRECC; National Institutes of Mental Health [5RO1 MH050787-10]; Department of Defense DAMD [17-01-1-0760] FX The authors wish to acknowledge Pamela Staves, C. N. S., N. P. for her assistance with study logistics. This research was supported by the Department of Veterans Affairs VISN 19 MIRECC and by the following grants to Dr. Adler: National Institutes of Mental Health 5RO1 MH050787-10 and Department of Defense DAMD 17-01-1-0760. There are no conflicts of interest to report. NR 29 TC 19 Z9 18 U1 2 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD OCT PY 2008 VL 14 IS 8 BP 939 EP 945 DI 10.1089/acm.2007.0814 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 374FN UT WOS:000261028700011 PM 18823261 ER PT J AU Brenes, GA Knudson, M McCall, WV Williamson, JD Miller, ME Stanley, MA AF Brenes, Gretchen A. Knudson, Mark McCall, W. Vaughn Williamson, Jeff D. Miller, Michael E. Stanley, Melinda A. TI Age and racial differences in the presentation and treatment of Generalized Anxiety Disorder in primary care SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE age differences; anxiety; elderly; Generalized Anxiety Disorder; racial differences ID STATE WORRY QUESTIONNAIRE; OLDER-ADULTS; UNITED-STATES; PANIC DISORDER; PSYCHOMETRIC PROPERTIES; ETHNIC-DIFFERENCES; AFRICAN-AMERICANS; MENTAL-DISORDERS; BODY-COMPOSITION; NEGATIVE AFFECT AB Despite the prevalence and impact of Generalized Anxiety Disorder (GAD) in the primary care setting, little is known about its presentation in this setting. The purpose of this study is to examine age and racial differences in the presentation and treatment of GAD in medical patients. Participants were recruited from one family medicine clinic and one internal medicine clinic. The prevalence of GAD was lowest for older adults. Age differences were found in the presentation of GAD, with young adults reporting greater cognitive symptoms of anxiety, negative affect, and depressive symptoms. African-Americans with GAD reported more positive affect and lower rates of treatment. The lower levels of negative affect and depressive symptoms reported among older adults may affect the recognition of GAD by primary care physicians. Further research is needed to better understand the causes of racial differences in treatment. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Brenes, Gretchen A.; McCall, W. Vaughn] Wake Forest Univ, Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC 27157 USA. [Knudson, Mark] Wake Forest Univ, Sch Med, Dept Family & Community Med, Winston Salem, NC 27157 USA. [Williamson, Jeff D.] Wake Forest Univ, Sch Med, Dept Internal Med, Sect Geriatr, Winston Salem, NC 27157 USA. [Williamson, Jeff D.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27157 USA. [Miller, Michael E.] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA. [Stanley, Melinda A.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Stanley, Melinda A.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. RP Brenes, GA (reprint author), Wake Forest Univ, Sch Med, Dept Psychiat & Behav Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM gbrenes@wfubmc.edu FU NIA NIH HHS [P30 AG021332]; NIMH NIH HHS [K23 MH065281, MH 65281, K23 MH065281-01A2] NR 55 TC 19 Z9 20 U1 4 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD OCT PY 2008 VL 22 IS 7 BP 1128 EP 1136 DI 10.1016/j.janxdis.2007.11.011 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 347AJ UT WOS:000259110700004 PM 18182275 ER PT J AU Scher, CD McCreary, DR Asmundson, GJG Resick, PA AF Scher, Christine D. McCreary, Donald R. Asmundson, Gordon J. G. Resick, Patricia A. TI The structure of post-traumatic stress disorder symptoms in three female trauma samples: A comparison of interview and self-report measures SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE factor structure; measurement; post-traumatic stress disorder; psychological assessment; test validity; trauma ID CONFIRMATORY FACTOR-ANALYSIS; ADMINISTERED PTSD SCALE; CHECKLIST-CIVILIAN VERSION; WORLD-TRADE-CENTER; FIT INDEXES; DIMENSIONALITY; VALIDATION; CHILDREN; CLUSTERS; VALIDITY AB Empirical research increasingly suggests that post-traumatic stress disorder (PTSD) is comprised of four factors: re-experiencing, avoidance, numbing, and hyperarousal. Nonetheless, there remains some inconsistency in the findings of factor analyses that form the bulk of this empirical literature. One source of such inconsistency may be assessment measure idiosyncrasies. To examine this issue, we conducted confirmatory factor analyses of interview and self-report data across three trauma samples. Analyses of the interview data indicated a good fit for a four-factor model across all samples; analyses of the self-report data indicated an adequate fit in two of three samples. Overall, findings suggest that measure idiosyncrasies may account for some of the inconsistency in previous factor analyses of PTSD symptoms. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Scher, Christine D.] Calif State Univ Fullerton, Dept Psychol, Fullerton, CA 92834 USA. [Asmundson, Gordon J. G.] Univ Regina, Traumat Stress Grp, Regina, SK S4S 0A2, Canada. [Resick, Patricia A.] Boston Univ, Boston, MA 02215 USA. [Resick, Patricia A.] Boston VA Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [McCreary, Donald R.] York Univ, N York, ON M3J 1P3, Canada. RP Scher, CD (reprint author), Calif State Univ Fullerton, Dept Psychol, POB 6846, Fullerton, CA 92834 USA. EM cscher@fullerton.edu RI Asmundson, Gordon/C-8071-2011 FU NIMH NIH HHS [R01 MH055542-03, 1R01 MH 51509, R01 MH051509, 1R01 MH 46992, R01 MH055542, 1R01 MH 55542, R01 MH046992, R01 MH046992-05, R01 MH051509-10] NR 46 TC 10 Z9 10 U1 4 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD OCT PY 2008 VL 22 IS 7 BP 1137 EP 1145 DI 10.1016/j.janxdis.2007.11.012 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 347AJ UT WOS:000259110700005 PM 18206346 ER PT J AU Long, ME Elhai, JD Schweinle, A Gray, MJ Grubaugh, AL Frueh, BC AF Long, Mary E. Elhai, Jon D. Schweinle, Amy Gray, Matt J. Grubaugh, Anouk L. Frueh, B. Christopher TI Differences in posttraumatic stress disorder diagnostic rates and symptom severity between Criterion A1 and non-Criterion A1 stressors SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE posttraumatic stress disorder; Criterion A1; psychological assessment; emotional trauma; diagnosis ID LIFE EVENTS; TRAUMATIC STRESS; DSM-V; PTSD; DISTRESS; CATEGORY; EXPOSURE; VIOLENCE; VICTIMS; SCALES AB This study addresses the ongoing controversy regarding the definition of DSM-IV posttraumatic stress disorder's (PTSD) traumatic stressor criterion (A 1). A sample of 119 college students completed the PTSD Symptom Scale separately in relation to both Criterion A1 and non-Criterion A1 stressful events, using a mixed between-groups (administration order) and within-subjects (stressor type) design. Contrary to what was expected, analyses revealed that non-Criterion A1 events were associated with greater likelihood of "probable" PTSD diagnoses and a greater PTSD symptom frequency than Criterion A1 events. Symptom frequency relationships, however, were moderated by the order in which the measures were administered. The non-Criterion A1 PTSD scores were only higher when non-Criterion A1 measures were presented first in the administration order. Similar patterns of differences in PTSD scores between stressor types were also found across the three PTSD symptom criteria. Implications are discussed as to the ongoing controversy of the PTSD construct. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Long, Mary E.; Elhai, Jon D.] Univ S Dakota, Disaster Mental Hlth Inst, Dept Psychol, Vermillion, SD 57069 USA. [Schweinle, Amy] Univ S Dakota, Sch Educ, Div Counseling & Psychol, Vermillion, SD 57069 USA. [Gray, Matt J.] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Grubaugh, Anouk L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Grubaugh, Anouk L.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. RP Elhai, JD (reprint author), Univ S Dakota, Disaster Mental Hlth Inst, Dept Psychol, Vermillion, SD 57069 USA. EM jon.elhai@usd.edu OI Schweinle, Amy/0000-0002-5813-2423 NR 40 TC 38 Z9 38 U1 4 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD OCT PY 2008 VL 22 IS 7 BP 1255 EP 1263 DI 10.1016/j.janxdis.2008.01.006 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 347AJ UT WOS:000259110700015 PM 18281192 ER PT J AU Gaynes, BI Torczynski, E Varro, Z Grostern, R Perlman, J AF Gaynes, Bruce Ira Torczynski, Elise Varro, Zoltan Grostern, Richard Perlman, Jay TI Retinal toxicity of chloroquine hydrochloride administered by intraperitoneal injection SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE chloroquine; intraperitoneal; bioavailability; toxicity; retina ID DRUG; RETINOPATHY; LIVER AB Chloroquine is quinolone derivative known to exert dose-related retinal toxicity, albeit in a variable manner. It is thought that variability in the presentation of chloroquine retinopathy may be the result of perturbations in drug bioavailability subsequent to oral ingestion. In order to better understand the ramifications of bioavailability on the development of retinal injury subsequent to chloroquine use, this study investigated the relationship between retinal injury and chloroquine administration via intraperitoneal rather than oral administration. Four-week-old C57/6J mice underwent daily intraperitoneal injection of 10 mg kg(-1) chloroquine hydrochloride for a total of 62 days. Following treatment, tissue was fixed in preparation for analysis by light and transmission electron microscopy. Treated animals demonstrated marked abnormality of the outer retinal layers described as complete loss of the outer plexiform layer as well as photo-receptors and photoreceptor nuclei. The retinal pigmented epithelium demonstrated focal atrophy, loss of nuclei and pigment irregularity. Findings in the inner retina were notable for the loss of Muller cells and the presence of membranous cytoplasmic bodies. Retinae of control animals were entirely normal. In contrast to previous studies in the murine model examining chloroquine retinopathy subsequent to oral administration, this study suggests that intraperitoneal chloroquine administration facilitates retinal toxicity, presumably, due to heightened drug absorption and bioavailability. It is posited that an increased rate of drug accumulation within the retina leads to an enhanced lysosomotrophic drug effect due to inability of the lysosome to compensate for chloroquine-induced elevation in pH through re-acidification of the intra-lysosomal content. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Gaynes, Bruce Ira; Torczynski, Elise; Varro, Zoltan; Grostern, Richard] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Perlman, Jay] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Gaynes, BI (reprint author), Rush Univ, Med Ctr, 1725 W Harrison,Suite 931, Chicago, IL 60612 USA. EM bgaynes@rush.edu NR 20 TC 6 Z9 8 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD OCT PY 2008 VL 28 IS 7 BP 895 EP 900 DI 10.1002/jat.1353 PG 6 WC Toxicology SC Toxicology GA 360QR UT WOS:000260072900009 PM 18484088 ER PT J AU Oral, E Malhi, AS Wannomae, KK Muratoglu, OK AF Oral, Ebru Malhi, Arnaz S. Wannomae, Keith K. Muratoglu, Orhun K. TI Highly cross-linked ultrahigh molecular weight polyethylene with improved fatigue resistance for total joint arthroplasty - Recipient of the 2006 Hap Paul Award SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total knee arthroplasty; highly cross-linked polyethylene; oxidation resistance; fatigue resistance; vitamin E; biomaterials ID ALPHA-TOCOPHEROL; CLINICAL-PERFORMANCE; GAMMA-STERILIZATION; IRRADIATED UHMWPE; PROPAGATION RESISTANCE; MECHANICAL-PROPERTIES; TIBIAL COMPONENTS; WEAR-RESISTANCE; VITAMIN-E; OXIDATION AB Eliminating postirradiation melting and stabilizing the residual free radicals of radiation cross-linked ultrahigh molecular weight polyethylene (UHMWPE) with vitamin E resulted in improved fatigue crack propagation resistance without compromising wear resistance. We designed a cantilever postbending test to determine the bending fatigue resistance of a-tocopherol-doped, irradiated UHMWPE (alpha-TPE) in comparison to conventional UHMWPE. The bending fatigue behavior of alpha-TPE was comparable to conventional UHMWPE. Upon accelerated aging, the fatigue resistance of alpha-TPE was substantially better than that of conventional UHMWPE. alpha-TPE has shown improved wear and oxidation resistance, migration stability of vitamin E, and improved mechanical properties. The use of this material may be beneficial in total knee arthroplasty where its improved fatigue properties may be an advantage under high stresses. C1 [Oral, Ebru; Malhi, Arnaz S.; Wannomae, Keith K.; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Boston, MA USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. FU NIH/NIAMS [AR051142]; Biomet, Inc. FX Research funding was received from NIH/NIAMS grant AR051142 and Biomet, Inc. In addition, one of the authors has received royalties from Biomet, Inc. NR 32 TC 27 Z9 28 U1 1 U2 11 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2008 VL 23 IS 7 BP 1037 EP 1044 DI 10.1016/j.arth.2007.09.027 PG 8 WC Orthopedics SC Orthopedics GA 357OJ UT WOS:000259855700015 PM 18547783 ER PT J AU Kuusikko, S Pollock-Wurman, R Jussila, K Carter, AS Mattila, ML Ebeling, H Pauls, DL Moilanen, I AF Kuusikko, Sanna Pollock-Wurman, Rachel Jussila, Katja Carter, Alice S. Mattila, Marja-Leena Ebeling, Hanna Pauls, David L. Moilanen, Irma TI Social anxiety in high-functioning children and adolescents with autism and Asperger syndrome SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Asperger syndrome; high-functioning autism; social anxiety; social phobia ID PHOBIA; DISORDERS; VALIDITY; SPECTRUM; PREVALENCE; MORBIDITY; CHECKLIST; BEHAVIOR; FAMILY; SAMPLE AB We examined social anxiety and internalizing symptoms using the Social Phobia and Anxiety Inventory for Children (SPAI-C), the Social Anxiety Scale for Children -Revised (SASC-R), and the Child Behavior Checklist (CBCL) in a sample of fifty-four high-functioning subjects with autism or Asperger syndrome (HFA/AS) (M = 11.2 +/- 1.7 years) and 305 community subjects (M = 12.2 +/- 2.2 years). Children and adolescents completed the SPAI-C and SASC-R, and their parents completed the CBCL Internalizing scale. Adolescents with HFA/AS scored higher than the community sample on all measures. Behavioural avoidance and evaluative social anxiety increased by age within the HFA/AS group, whereas behavioural avoidance decreased by age in control participants. Data support that HFA/AS in adolescents may be associated with clinically relevant social anxiety symptoms. C1 [Kuusikko, Sanna] Univ Hosp Oulu, Child Psychiat Clin, Oys Oulu 90029, Finland. [Pollock-Wurman, Rachel; Pauls, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Carter, Alice S.] Univ Massachusetts, Boston, MA 02125 USA. [Kuusikko, Sanna; Jussila, Katja; Mattila, Marja-Leena; Ebeling, Hanna; Moilanen, Irma] Univ Oulu, Clin Child Psychiat, Oulu, Finland. [Kuusikko, Sanna; Jussila, Katja; Mattila, Marja-Leena; Ebeling, Hanna; Moilanen, Irma] Univ Hosp Oulu, Oulu, Finland. RP Kuusikko, S (reprint author), Univ Hosp Oulu, Child Psychiat Clin, POB 26, Oys Oulu 90029, Finland. EM kuusisan@paju.oulu.fi NR 51 TC 126 Z9 129 U1 2 U2 41 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD OCT PY 2008 VL 38 IS 9 BP 1697 EP 1709 DI 10.1007/s10803-008-0555-9 PG 13 WC Psychology, Developmental SC Psychology GA 355TV UT WOS:000259732500010 PM 18324461 ER PT J AU Ciccarese, P Wu, E Wong, G Ocana, M Kinoshita, J Ruttenberg, A Clark, T AF Ciccarese, Paolo Wu, Elizabeth Wong, Gwen Ocana, Marco Kinoshita, June Ruttenberg, Alan Clark, Tim TI The SWAN biomedical discourse ontology SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Ontology; Semantic web; Scientific discourse; Biomedicine; SWAN; Alzheimer Disease; Knowledgebase ID SEMANTIC-WEB AB Developing cures for highly complex diseases, such as neurodegenerative disorders, requires extensive interdisciplinary collaboration and exchange of biomedical information in context. Our ability to exchange such information across sub-speciaities today is limited by the Current scientific knowledge ecosystem's inability to properly contextualize and integrate data and discourse in machine-interpretable form. This inherently limits the productivity of research and the progress toward cures for devastating diseases Such as Alzheimer's and Parkinson's. SWAN (Semantic Web Applications in Neuromedicine) is an interdisciplinary project to develop a practical, common, semantically structured, framework for biomedical discourse initially applied, but not limited, to significant problems in Alzheimer Disease (AD) research. The SWAN ontology has been developed in the context of building a series of applications for biomedical researchers, as well as in extensive discussions and collaborations with the larger bio-ontologies community. In this paper, we present and discuss the SWAN ontology of biomedical discourse. We ground its development theoretically, present its design approach, explain its main classes and their application, and show its relationship to other ongoing activities in biomedicine and bio-ontologies. (C) 2008 Elsevier Inc. All rights reserved. C1 [Clark, Tim] Harvard Initiat Innovat Comp, Cambridge, MA 02138 USA. [Ciccarese, Paolo; Ocana, Marco; Clark, Tim] Massachusetts Gen Hosp, Boston, MA 02129 USA. [Wu, Elizabeth; Wong, Gwen; Kinoshita, June] Alzheimer Res Forum Fdn, Boston, MA 02109 USA. [Ruttenberg, Alan] Sci Commons, Cambridge, MA 02139 USA. [Ciccarese, Paolo; Clark, Tim] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Clark, T (reprint author), Harvard Initiat Innovat Comp, 60 Oxford St,4th Floor, Cambridge, MA 02138 USA. EM tim_clark@harvard.edu OI Ruttenberg, Alan/0000-0002-1604-3078; Ciccarese, Paolo/0000-0002-5156-2703; Clark, Timothy/0000-0003-4060-7360 FU Ellison Medical Foundation; Alzheimer Association; Eli Lilly and Company FX We are grateful to the Ellison Medical Foundation, the Alzheimer Association, Eli Lilly and Company, and to an anonymous foundation, for their generous support of the SWAN project. NR 49 TC 54 Z9 54 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD OCT PY 2008 VL 41 IS 5 SI SI BP 739 EP 751 DI 10.1016/j.jbi.2008.04.010 PG 13 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 361OP UT WOS:000260137300007 PM 18583197 ER PT J AU Kim, SS Gwak, SJ Kim, BS AF Kim, Sang-Soo Gwak, So-Jung Kim, Byung-Soo TI Orthotopic bone formation by implantation of apatite-coated poly(lactide-co-glycolide)/hydroxyapatite composite particulates and bone morphogenetic protein-2 SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE bone regeneration; bone tissue engineering; bone morphogenetic protein; controlled release; hydroxyapatite; simulated body fluid ID SCAFFOLDS IN-VITRO; CONTROLLED-RELEASE; BIOMIMETIC PROCESS; HYDROXYAPATITE; POLYMERS; GROWTH; CARRIERS AB Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. However, a delivery system is essential to take advantage of the osteoinductive effect of BMPs. In the present study, we tested the suitability of apatite-coated poly(D,L-lactide-co-glycolide)/nanohydroxyapatite (PLGA/HA) particulates as carriers for the controlled release of BMP-2. The release of BMP-2 from apatite-coated PLGA/HA particulates was sustained for at least 4 weeks in vitro. A delivery system of apatite-coated PLGA/HA particulates suspended In fibrin gel further slowed the BMP-2 release rate. In vivo implantation of either Fibrin gel + BMP-2 or Fibrin gel + apatite-coated PLGA/HA particulates showed enhanced new bone formation in critical-sized calvarial defects of rats 8 weeks after implantation, compared to implantation of fibrin gel only. Importantly, new bone formation was Much higher in the defects treated with BMP-2 delivery using apatite-coated PLGA/HA particulates in fibrin gel (Fibrin gel + PLGA/HA + BMP-2 group) than in the defects treated either with apatite-coated PLGA/HA particulates in fibrin gel (Fibrin gel + BMP-2 group) or with BMP-2 delivery using fibrin gel alone (Fibrin gel + BMP-2 group). BMP-2 and osteoinductive HA had an additive effect on orthotopic bone formation. In conclusion, the apatite-coated PLGA/HA particulates showed good results as carriers for BMP-2. The BMP-2 delivery system showed high osteogenic capability in a rat calvarial bone defect model. The local and sustained delivery system for BMP-2 developed in this Study may be useful as a carrier for BMP-2 and would enhance bone regeneration efficacy for the treatment of large bone defects. (C) 2008 Wiley Periodicals, Inc. C1 [Kim, Sang-Soo; Kim, Byung-Soo] Hanyang Univ, Dept Bioengn, Seoul 133791, South Korea. [Kim, Sang-Soo] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Gwak, So-Jung] Hanyang Univ, Dept Chem Engn, Seoul 133791, South Korea. RP Kim, BS (reprint author), Hanyang Univ, Dept Bioengn, Seoul 133791, South Korea. EM bskim@hanyang.ac.kr RI kim, sang-soo/C-6573-2009; Kim, Byung-Soo/O-2352-2013 FU Ministry of Science and Technology; Republic of Korea (Stem Cell Research Center of the 21st Century Frontier) [SC 3220] FX Contract grant sponsor: Ministry of Science and Technology, Republic of Korea (Stem Cell Research Center of the 21st Century Frontier Program); contract grant number: SC 3220 NR 25 TC 42 Z9 47 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1549-3296 EI 1552-4965 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD OCT PY 2008 VL 87A IS 1 BP 245 EP 253 DI 10.1002/jbm.a.31782 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 347GV UT WOS:000259129500029 PM 18181112 ER PT J AU Song, MK Baik, YH Li, CJ Pei, CZ Gao, Y AF Song, Moon Ki Baik, Young Ho Li, Chang Jun Pei, Chang Zhuo Gao, Yuan TI Cyclo (his-pro) plus zinc treatment significantly ameliorated diabetes in humans SO JOURNAL OF BIOTECHNOLOGY LA English DT Meeting Abstract C1 [Song, Moon Ki] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. [Song, Moon Ki] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Baik, Young Ho; Li, Chang Jun; Pei, Chang Zhuo; Gao, Yuan] Yanbian Hanmi Med Ctr, Yanji, Jilin, Peoples R China. EM mksong@erathlink.net 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 0168-1656 EI 1873-4863 J9 J BIOTECHNOL JI J. Biotechnol. PD OCT PY 2008 VL 136 SU S MA I1-O-080 BP S25 EP S25 DI 10.1016/j.jbiotec.2008.07.045 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA V32VT UT WOS:000208979400053 ER PT J AU Lindenhovius, ALC Buijze, GA Kloen, P Ring, DC AF Lindenhovius, Anneluuk L. C. Buijze, Geert A. Kloen, Peter Ring, David C. TI Correspondence Between Perceived Disability and Objective Physical Impairment After Elbow Trauma SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID QUALITY-OF-LIFE; PAIN INTENSITY; HEALTH-STATUS; ADULT ATTACHMENT; DEPRESSION; FRACTURE; SURGERY; ARM; PREDICTORS; DISTRESS AB Background: Substantial differences between disability and impairment are commonplace and puzzling. Subjective (psychosocial) factors may be paramount given that pain is a more important determinant of perceived overall arm-specific disability than is objective elbow impairment. To further evaluate the relationship between impairment and disability, we tested the hypothesis that objective loss of elbow motion predicts perceived elbow-related task-specific disability better than does pain after elbow trauma. Methods: One hundred and fifty-eight patients were evaluated at a median of twenty-six months after a traumatic elbow injury and completed the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Predictors of the total DASH score and of the scores for individual DASH items that were expected to be related to elbow function were evaluated with univariate and multivariate analyses. Results: Motion accounted for 35% of the variability in the total DASH score, for 11% to 12% of the variability in the responses to questions specific to hand-based activities, and for 24% to 33% of the variability in the scores for tasks depending on elbow motion. Pain accounted for 41% of the variability in the total DASH score and was a better predictor than motion of disability associated with three tasks: opening a tight jar (with pain and motion accounting for 24% and 11% of the variability, respectively), pushing open a door (25% and 12%, respectively), and placing an object overhead (28% and 25%, respectively). None of the multivariate models explained more than 53% of the variability in the DASH scores. Conclusions: Objective physical elbow impairment correlated with self-reported disability with respect to specific tasks, but a large proportion of disability remains unexplained. Further research is needed to better understand the differences between objective impairment and perceived disability. C1 [Lindenhovius, Anneluuk L. C.; Buijze, Geert A.; Ring, David C.] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Kloen, Peter] Univ Amsterdam, Acad Med Ctr, NL-1100 DD Amsterdam, Netherlands. RP Lindenhovius, ALC (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 29 TC 32 Z9 32 U1 2 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD OCT PY 2008 VL 90A IS 10 BP 2090 EP 2097 DI 10.2106/JBJS.G.00793 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 357UV UT WOS:000259873300005 PM 18829905 ER PT J AU Hariri, S Bozic, KJ O'Connor, MI Rubash, HE AF Hariri, Sanaz Bozic, Kevin J. O'Connor, Mary I. Rubash, Harry E. TI Medicare Part B: Physician Participation Options SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID HEALTH-INSURANCE C1 [Hariri, Sanaz] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bozic, Kevin J.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [O'Connor, Mary I.] Mayo Clin, Dept Orthoped Surg, Jacksonville, FL 32224 USA. [Rubash, Harry E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hariri, S (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WHT 5-535, Boston, MA 02114 USA. EM sanaz@post.harvard.edu; bozick@orthosurg.ucsf.edu; oconnor.mary@mayo.edu; hrubash@partners.org NR 32 TC 2 Z9 2 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD OCT PY 2008 VL 90A IS 10 BP 2282 EP 2291 DI 10.2106/JBJS.H.00562 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 357UV UT WOS:000259873300027 PM 18829927 ER PT J AU Cotter, G Dittrich, HC Weatherley, BD Bloomfield, DM O'Connor, CM Metra, M Massie, BM AF Cotter, Gad Dittrich, Howard C. Weatherley, Beth Davison Bloomfield, Daniel M. O'Connor, Christopher M. Metra, Marco Massie, Barry M. CA Protect Steering Comm TI The PROTECT Pilot Study: A Randomized, Placebo-Controlled, Dose-Finding Study of the Adenosine A(1) Receptor Antagonist Rolofylline in Patients With Acute Heart Failure and Renal Impairment SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Adenosine receptor antagonists; chronic kidney disease; heart failure; renal function; rolofylline ID SYSTOLIC DYSFUNCTION; CLINICAL-TRIALS; KIDNEY-FUNCTION; BG9719 CVT-124; END-POINT; OUTCOMES; METAANALYSIS; RATIONALE; MORTALITY; EPILEPSY AB Background: Rolofylline, an adenosine A(1) receptor antagonist, facilitates diuresis and preserves renal function in patients with acute heart failure (AHF) with renal impairment. Although not powered around any specific hypothesis, this pilot study was designed to identify an efficacious dose while refining inclusion criteria and end points. Methods: A total of 301 patients hospitalized for AHF with an estimated creatinine clearance of 20 to 80 mL/min and elevated natriuretic peptide levels were enrolled within 24 hours of presentation to placebo or rolofylline 10, 20, or 30 mg administered as 4-hour infusions for 3 days in addition to intravenously administered loop diuretics. Post hoc analyses for end points chosen for subsequent Phase III studies were performed. Results: Compared with placebo, rolofylline produced trends toward greater proportions of patients with marked or moderately improved dyspnea and fewer patients with worsening heart failure or renal function. Serum creatinine increased in patients receiving placebo and remained stable or tended to decrease in those receiving rolofylline. On day 14 the absolute differences between placebo and rolofylline for change in creatinine increased with increasing rolofylline dose, reflecting the lesser increase in creatinine in rolofylline-treated patients (r = -0.12, P = .030). Treatment with 30 mg, the dose selected for the pivotal trials, was associated with a trend toward reduced 60-day mortality or readmission for cardiovascular or renal cause (hazard ratio, 0.55; 95% confidence interval, 0.28-1.04). Conclusion: These results demonstrate that adenosine A, receptor blockade with rolofylline can prevent renal impairment in patients with AHF and may positively affect acute symptoms and 60-day outcome. A 2000-patient trial of this agent is now under way. (J Cardiac Fail 2008;14:631-640) C1 [Massie, Barry M.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Cardiol, San Francisco, CA 94121 USA. [Cotter, Gad; Weatherley, Beth Davison] Momentum Res Inc, Durham, NC USA. [Dittrich, Howard C.] Nova Cardia Inc, San Diego, CA USA. [Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Metra, Marco] Univ Brescia, Brescia, Italy. RP Massie, BM (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Cardiol, 111C,4150 Clement St, San Francisco, CA 94121 USA. RI Zateyshchikov, Dmitry/D-6575-2012; Zadionchenko, Vladimir/A-7445-2016; Ponikowski, Piotr/O-6454-2015; OI Zateyshchikov, Dmitry/0000-0001-7065-2045; Zadionchenko, Vladimir/0000-0003-2377-5266; Ponikowski, Piotr/0000-0002-3391-7064; Davison, Beth/0000-0003-2374-6449; Metra, Marco/0000-0001-6691-8568 FU PROTECT [NCT00328692 (PROTECT-1), NCT00354458 (PROTECT-2)] FX The PROTECT study is registered on www.clinicaltrials.gov as NCT00328692 (PROTECT-1) and NCT00354458 (PROTECT-2). NR 30 TC 98 Z9 103 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2008 VL 14 IS 8 BP 631 EP 640 DI 10.1016/j.cardfail.2008.08.010 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 361NF UT WOS:000260133700001 PM 18926433 ER PT J AU Crimi, C Berra, L Kalra, A Allain, R Cambria, RP AF Crimi, Claudia Berra, Lorenzo Kalra, Aman Allain, Rae Cambria, Richard P. TI Fatal heparin-induced thrombocytopenia 8 months after prior exposure to heparin SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE heparin-induced thrombocytopenia; thrombocytopenia; thoracoabdominal aortic aneurysm ID THROMBOSIS; HISTORY AB HEPARIN-INDUCED THROMBOCYTOPENIA (HIT) is a syndrome of thrombocytopenia caused by circulating Ig antibodies ("HIT antibodies") that bind to heparin platelet factor 4 cornplexes.(1) HIT with thrombosis (HITT) is HIT with the clinical syndrome of arterial or venous thrombosis because of platelet activation. The frequency of development of HIT antibodies depends on the type of heparin exposure (higher with unfractionated hepanin [UFH] compared with low-molecular-weight heparin [LMWH]) and the patient population (surgical patients higher than medical patients). Cardiac surgical patients who are exposed to UFH perioperatively have a 50% incidence of detectable HIT antibodies.' In orthopedic surgical patients, the incidence is 15% with exposure to UFH but only 8% with exposure to LMWH.(1) Not all patients who develop HIT antibodies will become thrombocytopenic. Clinical HIT with thrombocytopenia below 100,0001/mu L is uncommon, and thrombosis (HITT) is rare (0%-5% of patients).(2-5) Thrombocytopenia develops generally within 4 to 15 days of exposure to heparin but occasionally call Occur within hours (rapid-onset HIT) because of the presence of circulating HIT antibodies formed after a recent exposure.(6-8) Of 73 patients identified to have had rapid-onset HIT over a period of 15 years, most had received heparin (all UFH) within the previous 3 weeks and all within the previous 100 days.(6) The authors describe a case of fatal rapid-onset HIT in a patient of previously unknown HIT status who had received UFH more than I year and LMWH 8 months before the current admission. C1 [Crimi, Claudia; Berra, Lorenzo; Allain, Rae] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Cambria, Richard P.] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Kalra, Aman] Tufts Univ, Sch Med, Dept Anesthesia, Tufts New England Med Ctr, Boston, MA 02111 USA. RP Allain, R (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM RAllain@partners.org FU R. Jenney Fund for Anesthesia and Critical Care Research FX Supported in part by the R. Jenney Fund for Anesthesia and Critical Care Research. NR 12 TC 0 Z9 1 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD OCT PY 2008 VL 22 IS 5 BP 732 EP 734 DI 10.1053/j.jvca.2007.10.003 PG 3 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 357OM UT WOS:000259856000015 PM 18922432 ER PT J AU Singh, BN AF Singh, Bramah N. TI Amiodarone as Paradigm for Developing New Drugs for Atrial Fibrillation SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Review DE amiodarone; atrial fibrillation; amiodarone congeners; dronedarone ID ANTI-ANGINAL DRUG; VENTRICULAR-FIBRILLATION; ANTIARRHYTHMIC-DRUGS; CARDIAC MUSCLE; SINUS RHYTHM; DRONEDARONE; PROFILE; AGENT; MECHANISMS; PREVENTION AB Introduced as an anti-anginal compound in 1962, amiodarone emerged in the 1970s as a uniquely effective antiarrhythmic and antifibrillatory drug with a multiplicity of properties, the most striking being the lengthening of the repolarization in the atria and ventricles associated with bradycardia but without a significant propensity for inducing torsade de pointes. Amiodarone is now the most frequently used agent for maintaining sinus rhythm in patients with AF. Its effectiveness for maintaining sinus rhythm remains unrivalled. Although the drug has few absolute contraindications to its use as an antiarrhythmic agent, limiting side effects such as thyroid dysfunction, pulmonary fibrosis, dermatological changes, and myriad lesser adverse effects often limit the use of the drug long-term in a proportion of patients. Thus, the idea has arisen that amiodarone might serve as a model for the synthesis and development of newer and novel antiarrhythmic agents devoid of organ toxicity. Amiodarone is an iodinated compound, and the possibility that its molecule may be modified with or without elimination of the iodine is being tested. The deletion of the iodine radical, substituting ethyl with butyl in the side chain of the aromatic ring, and adding a methylsulphonyl radical to the benzofuran component of the molecule leads to the loss of thyroid and pulmonary effects. The resulting compound, dronedarone, is in advanced clinical development. It is likely the first amiodarone congener that will be used in the control of atrial fibrillation. Others are in earlier phases of development. C1 [Singh, Bramah N.] VA Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA 90073 USA. [Singh, Bramah N.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Singh, BN (reprint author), VA Greater Los Angeles Healthcare Syst, Div Cardiol, 11301 Wils Blvd, Los Angeles, CA 90073 USA. EM bsingh@ucla.edu NR 38 TC 30 Z9 32 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD OCT PY 2008 VL 52 IS 4 BP 300 EP 305 DI 10.1097/FJC.0b013e31818914b6 PG 6 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 367ZB UT WOS:000260590000002 PM 18841075 ER PT J AU Ulu, A Davis, BB Tsai, HJ Kim, IH Morisseau, C Inceoglu, B Fiehn, O Hammock, BD Weiss, RH AF Ulu, Arzu Davis, Benjamin B. Tsai, Hsing-Ju Kim, In-Hae Morisseau, Christophe Inceoglu, Bora Fiehn, Oliver Hammock, Bruce D. Weiss, Robert H. TI Soluble Epoxide Hydrolase Inhibitors Reduce the Development of Atherosclerosis in Apolipoprotein E-Knockout Mouse Model SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE soluble epoxide hydrolase; 1-adamantan-3-(5-(2-(2-ethylethoxy)ethoxy)pentyl)urea; atherosclerosis; Apo E knockout mice; epoxycicosatrienoic acid ID II-INDUCED HYPERTENSION; LEUKOTOXIN 9,10-EPOXY-12-OCTADECENOATE; BLOOD-PRESSURE; MICE; DISEASE; RISK; INFLAMMATION; METABOLISM; TARGET; KIDNEY AB To determine whether sEH inhibitors influence atherosclerotic lesion formation, we used an established murine model of accelerated atherogenesis, ApoE knockout (-/-) mice. The sEH inhibitor, 1-adamantan-3-(5-(2-(2-ethylethoxy)ethoxy)pentyl)urea (AEPU) was delivered in drinking water. All animals were fed an atherogenic dict while simultaneously inflused with angiotensin II by osmotic minipump to induce atherosclerosis. In AEPU-treated animals, there was a 53% reduction in atherosclerotic lesions in the descending aortae as compared to control aortae. AEPU and its major metabolites were detected in the plasma of animals which received it. As expected from the inhibition of sEH, a significant increase in linoleic and arachidonic acid epoxides, as well as an increase in individual 11,12-EET/DHET ratios, were observed. The reduction in atherosclerotic lesion area was inversely correlated with 11,12- and 14,15- EET/DHET ratios, suggesting that the reduction corresponds to the inhibition of sEH. Our data suggest that orally-available sEH inhibitors may be useful in the treatment of patients with atherosclerotic cardiovascular disease. C1 [Weiss, Robert H.] Univ Calif Davis, Div Nephrol, Dept Internal Med, Canc Res Ctr, Davis, CA 95616 USA. [Ulu, Arzu; Tsai, Hsing-Ju; Kim, In-Hae; Morisseau, Christophe; Inceoglu, Bora; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Davis, Benjamin B.] Univ Calif Davis, Ctr Hlth & Environm, Davis, CA 95616 USA. [Fiehn, Oliver] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA. [Fiehn, Oliver] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. [Weiss, Robert H.] US Dept Vet Affairs, Med Ctr, Sacramento, CA USA. RP Weiss, RH (reprint author), Univ Calif Davis, Div Nephrol, Dept Internal Med, Canc Res Ctr, Genome & Biomed Sci Bldg,Room 6312, Davis, CA 95616 USA. EM rhweiss@ucdavis.edu OI Inceoglu, Bora/0000-0002-8473-6036 FU National Cancer Institute [IR21CA 91259-01AI]; U.S. Department of Veterans' Affairs; Phillip Morris Extramural Research [NIH ES011634, EPA R832414]; NIEHS [R37 ES02710, P42 ES004699, P01 ES11269]; NIH [HL85727]; NCRR-NIH [ULI RR024146]; Howard Hughes Medical Institute fellowship FX Supported by grant IR21CA 91259-01AI and the Early Detection Research Network from the National Cancer Institute; U.S. Department of Veterans' Affairs (RHW); the Phillip Morris Extramural Research Program; NIH ES011634 and EPA R832414 (BBD) and NIEHS grants R37 ES02710, P42 ES004699, and P01 ES11269, NIH HL85727 (BDH), UCD CTSC predoctoral clinical research training program fellowship NCRR-NIH ULI RR024146 (AU) and Howard Hughes Medical Institute fellowship (HJT). NR 36 TC 73 Z9 82 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD OCT PY 2008 VL 52 IS 4 BP 314 EP 323 DI 10.1097/FJC.0b013e318185fa3c PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 367ZB UT WOS:000260590000004 PM 18791465 ER PT J AU Sabbal, MJ Looper, JM Zavadzkas, JA Stroud, RE Ford, RL Rivers, WT Koval, CN McEvoy, MD Reeves, ST Spinale, FG AF Sabbal, Michel J. Looper, J. Michael Zavadzkas, Juozas A. Stroud, Robert E. Ford, Rachael L. Rivers, William T. Koval, Christine N. McEvoy, Matthew D. Reeves, Scott T. Spinale, Francis G. TI Aprotinin Exacerbates Left Ventricular Dysfunction After Ischemia/Reperfusion in Mice Lacking Tumor Necrosis Factor Receptor I SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE serine protease inhibitor; tumor necrosis factor; ischemia-reperfusion ID SYSTEMIC INFLAMMATORY RESPONSE; CARDIOPULMONARY BYPASS; CARDIAC-SURGERY; CUTTING EDGE; TNF-ALPHA; ECHOCARDIOGRAPHY; METAANALYSIS; INHIBITION; PERFUSION; MODELS AB Aprotinin is a serine protease inhibitor with diverse biological effects: until recently, it was utilized in the context of ischemia reperfusion (I/R). It has been hypothesized that a signaling pathway modulated by aprotinin in the context of I/R is the tumor necrosis factor-alpha receptor (TNFR) path-way. An intact Mouse model of I/R (30 min ischemia and 60 min reperfusion) was used and left ventricular (LV) peak + maximal rate of left ventricular (LV) peak pressure (dP/dt) was measured in wild-type mice (WT, C57BL/6; n = 10), WT mice with aprotinin (4 mL/kg; n = 10), transgenic mice devoid of the TNFRI (TNFRI-null; n = 10), and TNFRI-null with aprotinin (n=10). Following I/R, LV peak + dP/dt decreased in both WT groups, but remained similar to baseline values in the TNFRI-null group. In contrast, aprotinin caused a marked reduction in LV peak + dP/dt in the TNFRI-null group following I/R. Soluble plasma TNF levels increased in the WT and TNFRI-null mice with I/R and was reduced with aprotinin. Soluble TNFRI and TNFRII levels, indicative of TNF activation, increased in the WT mice following I/R and remained elevated with aprotinin. Soluble TNFRII levels were increased in the TNFRI-null mice following I/R and remained elevated with aprotinin. The new and unique findings of this study were twofold. First, aprotinin failed to improve LV function after I/R despite a reduction in circulating TNF levels. Second. genetic ablation of TNFRI uncovered a negative inotropic effect of aprotinin. These findings demonstrate that complex biological pathways and interactions are affected with broad spectrum serine protease inhibition, which are relevant to myocardial function in the context of I/R. C1 [Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Dept Cardiothorac Surg, Charleston, SC 29403 USA. [Sabbal, Michel J.; Looper, J. Michael; McEvoy, Matthew D.; Reeves, Scott T.] Med Univ S Carolina, Dept Anesthesiol & Perioperat Med, Charleston, SC 29403 USA. [Spinale, Francis G.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Dept Cardiothorac Surg, 114 Doughty St,Room 625, Charleston, SC 29403 USA. EM wilburnm@musc.edu FU National Heart. Lung, and Blood Institute [POI-HL-48788, ROI-HL-59165]; Research Service of the Department of Veterans Affairs; Bayer Pharmaceuticals; Foundation for Anesthesia Education and Research FX Supported by the National Heart. Lung, and Blood Institute (POI-HL-48788 and ROI-HL-59165 to F.G.S.), Research Service of the Department of Veterans Affairs (to F.G.S.). Research Fellowships from Bayer Pharmaceuticals (to M.D.M..), and the Foundation for Anesthesia Education and Research (to M.D.M.). NR 36 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD OCT PY 2008 VL 52 IS 4 BP 355 EP 362 DI 10.1097/FJC.0b013e3181893659 PG 8 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 367ZB UT WOS:000260590000009 PM 18841074 ER PT J AU Meng, Z Jackson, NL Choi, H King, PH Emanuel, PD Blume, SW AF Meng, Zheng Jackson, Nateka L. Choi, Hyoungsoo King, Peter H. Emanuel, Peter D. Blume, Scott W. TI Alterations in RNA-binding activities of IRES-regulatory proteins as a mechanism for physiological variability and pathological dysregulation of IGF-IR translational control in human breast tumor cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GROWTH-FACTOR-I; INTERNAL RIBOSOME ENTRY; NUCLEAR RIBONUCLEOPROTEIN-C; 5' UNTRANSLATED REGION; OPEN READING FRAMES; MESSENGER-RNA; RECEPTOR GENE; 5'-UNTRANSLATED REGION; MEDIATED TRANSLATION; MULTIPLE-MYELOMA AB The type 1 insulin-like growth factor receptor (IGF-IR) is integrally involved in the control of cellular proliferation and survival. An internal ribosomal entry site (IRES) within the 1,038 nucleoticle 5'-untranslated region of the human IGF-IR mRNA helps to provide the tight control of IGF-IR expression necessary for maintenance of normal cellular and tissue homeostasis. The IRES maps to a discrete sequence of 85 nucleotides positioned just upstream of the IGF-IR initiation codon, allowing the ribosome to bypass the highly structured regions of the 5'-UTR as well as the upstream open reading frame. The authenticity of the IGF-IR IRES has been confirmed by its sensitivity to deletion of the promoter from a bicistronic reporter construct, and its resistance in a monocistronic reporter construct to co-expression of a viral 2A protease. We previously characterized HuR as a potent repressor of IGF-IR translation. Here we demonstrate that hnRNP C competes with HuR for binding the IGF-IR 5'-UTR and enhances IRES-mediated translation initiation in a concentration-dependent manner. We observed changes in binding of hnRNP C versus HuR to the IGF-IR 5'-UTR in response to physiological alterations in cellular environment or proliferative status. Furthermore, we have found distinct alterations in the pattern of protein binding to the IGF-IR 5'-UTR in human breast tumor cells in which IGF-IR IRES activity and relative translational efficiency are aberrantly increased. These results suggest that dysregulation of the IGF-IR IRES through changes in the activities of RNA-binding translation-regulatory proteins could be responsible for IGF-IR overexpression in a proportion of human breast tumors. C1 [Meng, Zheng; Emanuel, Peter D.; Blume, Scott W.] Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. [Jackson, Nateka L.; Choi, Hyoungsoo; Emanuel, Peter D.; Blume, Scott W.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [King, Peter H.] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [King, Peter H.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Emanuel, Peter D.; Blume, Scott W.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. RP Blume, SW (reprint author), Univ Alabama, Dept Biochem & Mol Genet, 1824 6th Ave S,WT1 508, Birmingham, AL 35294 USA. EM scott.blume@ccc.uab.edu OI Emanuel, Peter/0000-0002-9764-2434 FU National Cancer Institute [CA1 08886]; Breast Cancer Research Program DAMD [17-03-1-0207]; UAB SPORE FX The authors would like to thank Cornell Badorff for generously providing the coxsackie virus B3 2A protease expression plasmid, and Gideon Dreyfuss for generously providing the hnRNP C expression vector and 4F4 antibody. This work was supported by Public Health Service Grant CA1 08886 from the National Cancer Institute, the Breast Cancer Research Program DAMD 17-03-1-0207 from the Department of Defense, and the UAB SPORE in Ovarian Cancer. NR 49 TC 30 Z9 30 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 2008 VL 217 IS 1 BP 172 EP 183 DI 10.1002/jcp.21486 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 344BJ UT WOS:000258899900019 PM 18452152 ER PT J AU Rosenzweig, JL Ferrannini, E Grundy, SM Haffner, SM Heine, RJ Horton, ES Kawamori, R AF Rosenzweig, James L. Ferrannini, Ele Grundy, Scott M. Haffner, Steven M. Heine, Robert J. Horton, Edward S. Kawamori, Ryuzo TI Primary prevention of cardiovascular disease and type 2 diabetes in patients at metabolic risk: An endocrine society clinical practice guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; IMPAIRED GLUCOSE-TOLERANCE; RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE INTERVENTION; C-REACTIVE PROTEIN; INSULIN-RESISTANCE SYNDROME; NON-HDL CHOLESTEROL; LIPID-LOWERING TREATMENT; HIGH-DOSE ATORVASTATIN AB Objective: The objective was to develop clinical practice guidelines for the primary prevention of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) in patients at metabolic risk. Conclusions: Healthcare providers should incorporate into their practice concrete measures to reduce the risk of developing CVD and T2DM. These include the regular screening and identification of patients at metabolic risk (at higher risk for both CVD and T2DM) with measurement of blood pressure, waist circumference, fasting lipid profile, and fasting glucose. All patients identified as having metabolic risk should undergo 10-yr global risk assessment for either CVD or coronary heart disease. This scoring will determine the targets of therapy for reduction of apolipoprotein B-containing lipoproteins. Careful attention should be given to the treatment of elevated blood pressure to the targets outlined in this guideline. The prothrombotic state associated with metabolic risk should be treated with lifestyle modification measures and in appropriate individuals with low-dose aspirin prophylaxis. Patients with prediabetes (impaired glucose tolerance or impaired fasting glucose) should be screened at 1-to 2-yr intervals for the development of diabetes with either measurement of fasting plasma glucose or a 2-h oral glucose tolerance test. For the prevention of CVD and T2DM, we recommend that priority be given to lifestyle management. This includes antiatherogenic dietary modification, a program of increased physical activity, and weight reduction. Efforts to promote lifestyle modification should be considered an important component of the medical management of patients to reduce the risk of both CVD and T2DM. C1 [Rosenzweig, James L.] Boston Med Ctr, Boston, MA 02118 USA. [Rosenzweig, James L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Ferrannini, Ele] Univ Pisa Sch, I-56126 Pisa, Italy. [Grundy, Scott M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78249 USA. [Heine, Robert J.] Vrije Univ Amsterdam, Ctr Med, NL-1081 Amsterdam, Netherlands. [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kawamori, Ryuzo] Juntendo Univ, Sch Med, Tokyo 1138421, Japan. RP Rosenzweig, JL (reprint author), Boston Med Ctr, Boston, MA 02118 USA. NR 147 TC 89 Z9 96 U1 0 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2008 VL 93 IS 10 BP 3671 EP 3689 DI 10.1210/jc.2008-0222 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 358FY UT WOS:000259903700003 PM 18664543 ER PT J AU Kahn, SE Cefalu, WT AF Kahn, Steven E. Cefalu, William T. TI Glucose control, macro- and microvascular disease, and the food and drug administration: Let's keep our eye on the ball SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; RISK; ROSIGLITAZONE; COMPLICATIONS; SULFONYLUREAS; METFORMIN; DEATH C1 [Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98108 USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98108 USA. [Cefalu, William T.] Pennington Biomed Res Ctr, Div Nutr & Chron Dis, Baton Rouge, LA 70808 USA. RP Kahn, SE (reprint author), Vet Affairds Puger Sound Hlth Care Syst 151,1660, Seattle, WA 98108 USA. EM skahn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 NR 12 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2008 VL 93 IS 10 BP 3727 EP 3729 DI 10.1210/jc.2008-1799 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 358FY UT WOS:000259903700009 PM 18765506 ER PT J AU Utz, AL Yamamoto, A Sluss, P Breu, J Miller, KK AF Utz, A. L. Yamamoto, A. Sluss, P. Breu, J. Miller, K. K. TI Androgens may mediate a relative preservation of IGF-I levels in overweight and obese women despite reduced growth hormone secretion SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; CLINICAL-RESEARCH CENTER; ABDOMINAL VISCERAL FAT; GH-BINDING PROTEIN; POSTMENOPAUSAL WOMEN; HEALTHY-ADULTS; DEHYDROEPIANDROSTERONE-SULFATE; HYPOGONADOTROPIC HYPOGONADISM; INSULIN CONCENTRATIONS; TRANSDERMAL ESTROGEN AB Context: Obesity is characterized by reduced GH secretion, but data regarding IGF-I levels and their determinants are conflicting. Objectives: The objectives were to determine whether IGF-I levels are reduced and to investigate determinants of GH and IGF-I in healthy overweight and obese women. Design: A cross-sectional study was performed. Setting: The study was conducted at a General Clinical Research Center. Study Participants: Thirty-four healthy women without pituitary/hypothalamic disease participated, including 11 lean [body mass index (BMI) < 25 kg/m(2)], 12 overweight (BMI < 25 kg/m(2) and <30 kg/m(2)), and 11 obese (BMI >= 30 kg/m(2)) women of comparable age (overall mean age, 30.7 +/- 7.8 yr). Intervention: There was no intervention. Main Outcome Measures: The main outcome measures were frequent sampling (every 10 min for 24 h) for GH, peak GH after GHRH-arginine stimulation, IGF-I, IGF binding protein-3, estrone, estradiol, testosterone, free testosterone, SHBG, homeostasis model assessment of insulin resistance, and abdominal fat. Results: Mean 24-h GH and peak stimulated GH were lower in overweight than lean women and lowest in obese women. Mean IGF-I levels trended lower in obese, but not overweight, compared with lean women. Free testosterone was positively associated with IGF-I (R = 0.36, P = 0.04) but not with GH measures. Visceral fat was the only determinant of mean 24-h GH (R-2 = 0.66, P < 0.0001) and of peak stimulated GH (R-2 = 0.63, P < 0.0001), and mean 24-h GH accounted for 39% of the variability of IGF-I (P = 0.0002), with an additional 28% (P < 0.0001) attributable to free testosterone levels. Conclusions: Despite a linear decrease in GH secretion and peak stimulated GH levels with increasing BMI in healthy overweight and obese women, IGF-I levels were not commensurately reduced. Androgens may contribute to this relative preservation of IGF-I secretion in overweight and obese women despite reduced GH secretion. C1 [Utz, A. L.; Yamamoto, A.; Miller, K. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. [Sluss, P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sluss, P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Breu, J.] MIT, Clin Res Ctr, Cambridge, MA 02139 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Bulfinch 457B, Boston, MA 02114 USA. EM KKMiller@Partners.org RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU National Institutes of Health [RO1 HL077674, MO1 RR01066] FX We thank the nurses and bionutritionists of the Massachusetts General Hospital General Clinical Research Center and the study subjects who participated in the study.; Address all correspondence and requests for reprints to: Karen K. Miller, Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: KKMiller@Partners.org.; This work was supported in part by National Institutes of Health Grants RO1 HL077674 and MO1 RR01066.; Disclosure Statement: The authors have no conflicts to declare. NR 53 TC 15 Z9 15 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2008 VL 93 IS 10 BP 4033 EP 4040 DI 10.1210/jc.2008-0930 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 358FY UT WOS:000259903700054 PM 18647804 ER PT J AU Boni-Schnetzler, M Thorne, J Parnaud, G Marselli, L Ehses, JA Kerr-Conte, J Pattou, F Halban, PA Weir, GC Donath, MY AF Boni-Schnetzler, Marianne Thorne, Jeffrey Parnaud, Geraldine Marselli, Lorella Ehses, Jan A. Kerr-Conte, Julie Pattou, Francois Halban, Philippe A. Weir, Gordon C. Donath, Marc Y. TI Increased interleukin (IL)-1 beta messenger ribonucleic acid expression in beta-cells of individuals with type 2 diabetes and regulation of IL-1 beta in human islets by glucose and autostimulation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LASER CAPTURE MICRODISSECTION; HUMAN PANCREATIC-ISLETS; SMOOTH-MUSCLE CELLS; RECEPTOR ANTAGONIST; GENE-EXPRESSION; INFLAMMATORY MEDIATORS; INSULIN-SECRETION; PSAMMOMYS-OBESUS; INDUCTION; DEATH AB Context: Elevated glucose levels impair islet function and survival, and it has been proposed that intraislet expression of IL-1 beta contributes to glucotoxicity. Objective: The objective was to investigate IL-1 beta mRNA expression in near-pure beta-cells of patients with type 2 diabetes (T2DM) and study the regulation of IL-1 beta by glucose in isolated human islets. Methods: Laser capture microdissection was performed to isolate beta-cells from pancreas sections of 10 type 2 diabetic donors and nine controls, and IL-1 beta mRNA expression was analyzed using gene arrays and PCR. Cultured human islets and fluorescence-activated cell sorter-purified human beta-cells were used to study the regulation of IL-1 beta expression by glucose and IL-1 beta. Results: Gene array analysis of RNA from beta-cells of individuals with T2DM revealed increased expression of IL-1 beta mRNA. Real-time PCR confirmed increased IL-1 beta expression in six of 10 T2DM samples, with minimal or no expression in nine control samples. In cultured human islets, IL-1 beta mRNA and protein expression was induced by high glucose and IL-1 beta autostimulation and decreased by the IL-1 receptor antagonist IL-1Ra. The glucose response was negatively correlated with basal IL-1 beta expression levels. Autostimulation was transient and nuclear factor-kappa B dependent. Glucose-induced IL-1 beta was biologically active and stimulated IL-8 release. Low picogram per milliliter concentrations of IL-1 beta up-regulated inflammatory factors IL-8 and IL-6. Conclusion: Evidence that IL-1 beta mRNA expression is up-regulated in beta-cells of patients with T2DM is presented, and glucose-promoted IL-1 beta autostimulation may be a possible contributor. C1 [Boni-Schnetzler, Marianne] Univ Zurich Hosp, Dept Med, Clin Endocrinol & Diabet, CH-8091 Zurich, Switzerland. [Thorne, Jeffrey; Marselli, Lorella; Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Parnaud, Geraldine; Halban, Philippe A.] Univ Geneva, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Kerr-Conte, Julie; Pattou, Francois] Fac Med Lille, INSERM, UM859, F-59045 Lille, France. RP Boni-Schnetzler, M (reprint author), Univ Zurich Hosp, Dept Med, Clin Endocrinol & Diabet, CH-8091 Zurich, Switzerland. EM marianne.boeni@usz.ch FU Juvenile Diabetes Research Foundation [7-2005-1158]; European Foundation for the Study of Diabetes/Pfizer Resource; Swiss National Science Foundation; University Research Priority Program Integrative Human Physiology at the University of Zurich; European Foundation for the Study of Diabetes/Merck Sharp & Dohme basic research; National Institutes of Health (NCRR ICR) [U4Z RR 16606, U19DK6125]; American Diabetes Association; Diabetes Research and Wellness Foundation FX We thank G. Sigfried-Kellenberger for excellent technical assistance. Some batches of human islets of Langerhans were provided by the Cell Isolation and Transplantation Center at the University of Geneva School of Medicine, thanks to the ECIT Islets for Research distribution program sponsored by the Juvenile Diabetes Research Foundation. We thank P. Marchetti for providing us pancreas sections from T2D donors (supported by a European Foundation for the Study of Diabetes/Pfizer Resource Grant). Address all correspondence and requests for reprints to: Marianne Boni-Schnetzler, Ph.D., Clinic of Endocrinology and Diabetes, Department of Medicine, University Hospital, CH-8091 Zurich, Switzerland. E-mail: marianne.boeni@usz.ch.; The work of M.B.-S., J.A.E., and M.Y.D. was supported by grants from the Swiss National Science Foundation, the Juvenile Diabetes Research Foundation, the University Research Priority Program Integrative Human Physiology at the University of Zurich, and a European Foundation for the Study of Diabetes/Merck Sharp & Dohme basic research grant. The work of G.C.W., L.M., and J.T. was supported by grants from the National Institutes of Health (NCRR ICR U4Z RR 16606 and U19DK6125), the American Diabetes Association, and the Diabetes Research and Wellness Foundation. P.A.H. was supported by Grant 7-2005-1158 from the Juvenile Diabetes Research Foundation.; Disclosure Summary: M.B.-S., J.T., G.P., L.M., J.A.E., J.K.-C., F.P., P.A.H., G.C.W., and M.Y.D. have nothing to declare. NR 40 TC 147 Z9 157 U1 0 U2 10 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2008 VL 93 IS 10 BP 4065 EP 4074 DI 10.1210/jc.2008-0396 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 358FY UT WOS:000259903700059 PM 18664535 ER PT J AU Gejman, R Batista, DL Zhong, Y Zhou, YL Zhang, X Swearingen, B Stratakis, CA Hedley-Whyte, ET Klibanski, A AF Gejman, Roger Batista, Dalia L. Zhong, Ying Zhou, Yunli Zhang, Xun Swearingen, Brooke Stratakis, Constantine A. Hedley-Whyte, E. Tessa Klibanski, Anne TI Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DLK1-GTL2 IMPRINTED DOMAIN; PROMOTER REGION; GENE-EXPRESSION; TUMORS; MOUSE-CHROMOSOME-12; TUMORIGENESIS; MECHANISMS; IGF2-H19; CLUSTER; ORIGIN AB Context: MEG3 is an imprinted gene encoding a novel noncoding RNA that suppresses tumor cell growth. Although highly expressed in the normal human pituitary, it is unknown which of the normal pituitary cell types and pituitary tumors express MEG3. Objectives: Our objectives were 1) to investigate cell-type- and tumor-type-specific expression of MEG3 in the human pituitary and 2) to investigate whether methylation in the intergenic differentially methylated region (IG-DMR) at the DLK1/MEG3 locus is involved in the loss of MEG3 expression in tumors. Design and Methods: RT-PCR, quantitative RT-PCR, Northern blot, and a combination of in situ hybridization and immunofluorescence were used to determine the cell-type- and tumor-type-specific MEG3 expression. Bisulfite treatment and PCR sequencing of genomic DNA were used to measure the CpG methylation status in the normal and tumor tissues. Five normal human pituitaries and 17 clinically nonfunctioning, 11 GH-secreting, seven prolactin-secreting, and six ACTH-secreting pituitary adenomas were used. Results: All normal human pituitary cell types express MEG3. However, loss of MEG3 expression occurs only in nonfunctioning pituitary adenomas of a gonadotroph origin. All other pituitary tumor phenotypes examined express MEG3. Hypermethylation of the IG-DMR at the DLK1/MEG3 locus is present in nonfunctioning pituitary adenomas. Conclusions: MEG3 is the first human gene identified expressed in multiple normal human pituitary cell types with loss of expression specifically restricted to clinically nonfunctioning pituitary adenomas. The IG-DMR hypermethylation may be an additional mechanism for MEG3 gene silencing in such tumors. C1 [Gejman, Roger; Batista, Dalia L.; Zhong, Ying; Zhou, Yunli; Zhang, Xun; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Gejman, Roger; Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Neuropathol Unit, Boston, MA 02114 USA. [Swearingen, Brooke] Massachusetts Gen Hosp, Div Neurosurg, Boston, MA 02114 USA. [Swearingen, Brooke] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Stratakis, Constantine A.] NICHHD, Endocrinol Sect, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] NICHHD, Genet & Pediat Endocrinol Training Program, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,BUL457, Boston, MA 02114 USA. EM aklibanski@partners.org FU National Institutes of Health [R01-DK-40947]; The Jarislowsky Foundation; Pontificia Universidad Catolica de Chile and the Chilean Government FX Address all correspondence and requests for reprints to: Anne Klibanski, M. D., Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, BUL457, Boston, Massachusetts 02114. E-mail: aklibanski@partners.org.; This work was supported by National Institutes of Health Grant R01-DK-40947, The Jarislowsky Foundation, and scholarships from Pontificia Universidad Catolica de Chile and the Chilean Government (R.G.).; Disclosure Statement: B. S. has equity interests in Pfizer, Roche, and Novartis. E.T.H.-W. has equity interests in Becton Dickinson. The other authors have nothing to declare. NR 33 TC 57 Z9 58 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2008 VL 93 IS 10 BP 4119 EP 4125 DI 10.1210/jc.2007-2633 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 358FY UT WOS:000259903700066 PM 18628527 ER PT J AU Butt, AA Khan, UA Skanderson, M AF Butt, Adeel A. Khan, Uzma A. Skanderson, Melissa TI Comorbidities and their impact on mortality in HCV and HCV-HIV-coinfected persons on dialysis SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE HIV; dialysis; USRDS; survival ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC HEPATITIS-C; STAGE LIVER-DISEASE; HEMODIALYSIS-PATIENTS; PEGINTERFERON ALPHA-2A; PLUS RIBAVIRIN; UNITED-STATES; INFECTION; VETERANS; SURVIVAL AB Aim: To determine the rates of non-human immunodeficiency virus (HIV)-related comorbidities and their impact on survival in hepatitis C virus (HCV) and HCV-HIV coinfected persons oil dialysis. Methods: We identified HCV-infected subjects and diagnoses of medical and psychiatric comorbidities in the United States Renal Data System using ICD-9 codes. Logistic regression was used to determine the odds of comorbidities and predictors of mortality. Results: We identified 5310 HCV-infected and 427 HCV-HIV-coinfected subjects. The latter were younger, more likely to be male, black race, and had a lower body mass index. After adjusting for age, race and sex we found that coronary artery disease (CAD), diabetes mellitus (DM) as primary cause of renal failure and cirrhosis were less frequently diagnosed in the HCV- HIV-coinfected subjects, whereas hepatitis B, washing, drug and alcohol abuse, and dependence were more frequently diagnosed. Increasing age. CAD, stroke, DM. cirrhosis, wasting, cancer, and drug abuse and dependence were associated with higher odds of death in the HCV monoinfected subjects, whereas cirrhosis, wasting, and smoking were the only such factors in the HCV-HIV-coinfected subjects. Conclusions: The frequency and patterns of comorbidities and predictors of death differ in HCV-monoinfected and HCV- HIV-coinfected persons on dialysis. These differences should be taken into account when designing future interventions. C1 [Butt, Adeel A.] Univ Pittsburgh, Med Ctr, Div Infect Dis, Pittsburgh, PA 15213 USA. [Butt, Adeel A.; Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.] Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Khan, Uzma A.] Albany Med Ctr, Albany, NY USA. RP Butt, AA (reprint author), Univ Pittsburgh, Med Ctr, Div Infect Dis, MS 3601 5th Ave,Suite 3A,Falk Med Bldg, Pittsburgh, PA 15213 USA. EM butta@dom.pitt.edu NR 37 TC 6 Z9 6 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD OCT PY 2008 VL 42 IS 9 BP 1054 EP 1059 DI 10.1097/MCG.0b013e3181574d58 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 354RK UT WOS:000259656500015 PM 19013829 ER PT J AU Cushman, WC Ford, CE Einhorn, PT Wright, JT Preston, RA Davis, BR Basile, JN Whelton, PK Weiss, RJ Bastien, A Courtney, DL Hamilton, BP Kirchner, K Louis, GT Retta, TM Vidt, DG AF Cushman, William C. Ford, Charles E. Einhorn, Paula T. Wright, Jackson T., Jr. Preston, Richard A. Davis, Barry R. Basile, Jan N. Whelton, Paul K. Weiss, Robert J. Bastien, Arnaud Courtney, Donald L. Hamilton, Bruce P. Kirchner, Kent Louis, Gail T. Retta, Tamrat M. Vidt, Donald G. CA ALLHAT Collaborat Res Grp TI Blood Pressure Control by Drug Group in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID JOINT NATIONAL COMMITTEE; HYPERTENSION; OUTCOMES; CHLORTHALIDONE; MANAGEMENT; RECRUITMENT; POPULATION; CARDIOLOGY; ADULTS AB Blood pressure (BP) control rates and number of antihypertensive medications were compared (average follow-up, 4.9 years) by randomized groups: chlorthalidone, 12.5-25 mg/d (n=15,255), amlodipine 2.5-10 mg/d (n=9048), or lisinopril 10-40 mg/d (n=9054) in a randomized double-blind hypertension trial. Participants were hypertensives aged 55 or older with additional cardiovascular risk factor(s), recruited from 623 centers. Additional agents from other classes were added as needed to achieve BP control. BP was reduced from 145/83 mm Hg (27% control) to 134/76 mm Hg (chlorthalidone, 68% control), 135/75 mm Hg (amlodipine, 66% control), and 136176 mm Hg (lisinopril, 61% control) by 5 years; the mean number of drugs prescribed was 1.9, 2.0, and 2.1, respectively. Only 28% (chlorthalidone), 24% (amlodipine), and 24% (lisinopril) were controlled on monotherapy. BP control was achieved in the majority of each randomized group-a greater proportion with chlorthalidone. Over time, providers and patients should expect multidrug therapy to achieve BP < 140/90 mm Hg in a majority of patients. J Clin Hypertens (Greenwich). 2008;1.0:751-760. (c) 2008 Le Jacq C1 [Ford, Charles E.; Davis, Barry R.] Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX 77030 USA. [Cushman, William C.] Vet Affairs Med Ctr, Memphis, TN USA. [Einhorn, Paula T.] NHLBI, Bethesda, MD 20892 USA. [Wright, Jackson T., Jr.] Univ Hosp Cleveland, Gen Clin Res Ctr, Cleveland, OH 44106 USA. [Preston, Richard A.] Vet Affairs Med Ctr, Miami, FL 33125 USA. [Basile, Jan N.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Whelton, Paul K.] Loyola Univ, Hlth Syst & Med Ctr, Maywood, IL 60153 USA. [Weiss, Robert J.] Androscoggin Cardiol Associates, Auburn, ME USA. [Bastien, Arnaud] Bristol Myers Squibb Co, Princeton, NJ USA. [Courtney, Donald L.] DD Eisenhower Vet Affairs Med Ctr, Leavenworth, KS USA. [Hamilton, Bruce P.] Vet Affairs Med Ctr, Baltimore, MD USA. [Kirchner, Kent] Vet Affairs Med Ctr, Jackson, MS USA. [Louis, Gail T.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. [Retta, Tamrat M.] Howard Univ, Hypertens & Lipid Clin, Washington, DC 20059 USA. [Vidt, Donald G.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Ford, CE (reprint author), Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, 1200 Hermann Pressler, Houston, TX 77030 USA. EM charles.e.ford@uth.tmc.edu FU National Heart, Lung, and Blood Institute [N0.1-HC-35130]; National Institutes of Health, US Department of Health and Human Services, Bethesda, MD; AstraZeneca; GlaxoSmithKline; Novartis FX This research was supported by Health and Human Services contract number N0.1-HC-35130 from the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD. The ALLHAT investigators acknowledge contributions of study medications supplied by Pfizer, Inc (amlodipine), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin) and financial support provided by Pfizer, Inc. JNB has consulted for Novartis and Sankyo and has received honoraria from AstraZeneca and Pfizer. WCC has consulted for Calpis, King, Myogen, Novartis, Pfizer, Roche, Sankyo, Sanofi Aventis and Takeda and has received honoraria from AstraZeneca, Boehringer Ingelheini, Forest Pharmaceuticals, Novartis, and Sankyo. He has also received research grants from Abbott 14 Laboratories and Novartis. BRD has consulted for BioMarin, GlaxoSmithKline, Proctor and Gamble, and Takeda. CEF has consulted for BioMarin. RAP has received researched grants from Berlex, Bristol-Myers Squibb, Ferring, Novartis, Schering Plough, Takeda, and Wyeth and has received honoraria from is Berlex, Ferring, and Pfizer. DGV has consulted for AstraZeneca, received honoraria from AstraZeneca and Merck, and has received a research grant from Boehringer Ingelheim. JTW has consulted for GlaxoSmithKline, Novartis, PfiZer, and Sanofi-Synthelabo; has received honoraria from GlaxoSmithKline; and has received research grants from GlaxoSmithKline and Novartis. The rest of the authors have no financial interests to disclose. NR 31 TC 43 Z9 45 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD OCT PY 2008 VL 10 IS 10 BP 751 EP 760 DI 10.1111/j.1751-7176.2008.00015.x PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 381XN UT WOS:000261569300003 PM 19090876 ER PT J AU Furmaga, EM Cunningham, FE Cushman, WC Dong, D Jiang, R Basile, J Katz, LA Rutan, GH Berlowitz, DR Papademetriou, V Glassman, PA AF Furmaga, Elaine M. Cunningham, Francesca E. Cushman, William C. Dong, Diane Jiang, Rang Basile, Jan Katz, Lois A. Rutan, Gale H. Berlowitz, Dan R. Papademetriou, Vasilios Glassman, Peter A. TI National Utilization of Antihypertensive Medications From 2000 to 2006 in the Veterans Health Administration: Focus on Thiazide Diuretics SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; MAJOR CARDIOVASCULAR EVENTS; HIGH BLOOD-PRESSURE; UNITED-STATES; HYPERTENSION; METAANALYSIS; OUTCOMES; ADULTS; PREVENTION AB The authors sought to determine the prescribing practices of clinicians treating veterans with hypertension. A descriptive analysis was performed using a national pharmacy database of patients with a diagnosis of hypertension receiving antihypertensive medication in the fiscal years 2000 to 2006. Angiotensin-converting enzyme inhibitors were the most frequently prescribed antihypertensive class, with utilization increasing from 56.0% in fiscal year 2000 to 63.2% of patients in 2006. Utilization of thiazide-type diuretics increased from 31.9% of patients in fiscal year 2000 to 42.0% in 2006. When patient comorbidities were taken into consideration, 48.1% of patients defined as having uncomplicated hypertension bad at least one prescription for a thiazide-type diuretic in fiscal year 2006. Utilization by monotherapy and combination therapy were also evaluated. The trends in utilization allowed for identification of areas in which a change in prescribing practices may improve blood pressure control and health outcomes in the Veterans Health Administration. J Clin Hypertens (Greenwich). 2008;10:770-778. (c) 2008 Le Jacq C1 [Furmaga, Elaine M.; Cunningham, Francesca E.] Vet Hlth Adm, Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL 60141 USA. [Cunningham, Francesca E.; Dong, Diane; Jiang, Rang] PBM Pharmacoepidemiol Outcomes Res, Hines, IL USA. [Cunningham, Francesca E.; Dong, Diane; Jiang, Rang; Glassman, Peter A.] Natl Ctr Medicat Safety, Hines, IL USA. [Cushman, William C.] Memphis VAMC, Prevent Med, Memphis, TN USA. [Basile, Jan] Ralph H Johnson VA Med Ctr, Primary Care Serv Line, Charleston, SC USA. [Katz, Lois A.] VA NY Harbor Healthcare Syst, Special Emphasis Programs & Qual Management, New York, NY USA. [Rutan, Gale H.] DC VAMC, Washington, DC USA. [Berlowitz, Dan R.] Bedford VA Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Berlowitz, Dan R.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Papademetriou, Vasilios] Vet Adm, Washington, DC USA. [Papademetriou, Vasilios] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Glassman, Peter A.] VHA PBM Med Advisory Panel, Hines, IL USA. [Glassman, Peter A.] Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [Glassman, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Furmaga, EM (reprint author), Vet Hlth Adm, Dept Vet Affairs, Pharm Benefits Management Serv, 119D,POB 126, Hines, IL 60141 USA. EM elaine.furmaga@va.gov OI Papademetriou, Vasilios/0000-0002-2882-2757 FU Novartis Pharmaceuticals; Abbott Laboratories; AstraZeneca FX We would like to acknowledge the contributions of Sandra M. Walsh, NM, VAMC Memphis, Hypertension/Lipids Research Section, and Roxane Ruscb, RN, BSN, MPA, clinical specialist for policy analysis and forecasting and VHA Office of the Assistant Deputy Under Secretary for Health for Policy and Planning, for their involvement on the Hypertension Field Advisory Committee. William C. Cushman, MD, has received grantl research support from Novartis Pharmaceuticals and Abbott Laboratories and is a consultant for and/or has received honoraria from AstraZeneca, Sanofi Aventis, Bristol-Myers Squibb, Novartis Pharmaceuticals, Pfizer Inc, Daiichi Sankyo, Forest Laboratories, King Pharmaceuticals, Boehringer Ingetheim, Roche Pharmaceuticals, Calpis Company Ltd, Myogen, Inc, and Takeda Pharmaceutical Company Ltd. Jan Basile, MD, has received grant/research support from Boehringer Ingelheim and Novartis Pharmaceuticals and is on the speaker's bureau for AstraZeneca, Boehringer Ingetheim, Daiichi Sankyo, Forest Laboratories, Merck, and Novartis Pharmaceuticals. Lois A. Katz, MD, has received grantl research support from Boehringer Ingetheim, Abbott Laboratories, and Kos Pharmaceuticals and honoraria from Novartis Pharmaceuticals. Dan R. Berlowitz, MD, has received grant/research support from Bristol-Myers Squibb and Sanofi Aventis and honoraria from Bristol-Myers Squibb. Vasilios Papademetriou, MD, has received grant/research support from AstraZeneca and honoraria from AstraZeneca and Novartis Pharmaceuticals. NR 32 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD OCT PY 2008 VL 10 IS 10 BP 770 EP 778 DI 10.1111/j.1751-7176.2008.00019.x PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 381XN UT WOS:000261569300005 PM 19090878 ER PT J AU Lewis, GD Wei, R Liu, E Yang, E Shi, X Martinovic, M Farrell, L Asnani, A Cyrille, M Ramanathan, A Shaham, O Berriz, G Lowry, PA Palacios, IF Tasan, M Roth, FP Min, JY Baumgartner, C Keshishian, H Addona, T Mootha, VK Rosenzweig, A Carr, SA Fifer, MA Sabatine, MS Gerszten, RE AF Lewis, Gregory D. Wei, Ru Liu, Emerson Yang, Elaine Shi, Xu Martinovic, Maryann Farrell, Laurie Asnani, Aarti Cyrille, Marcoli Ramanathan, Arvind Shaham, Oded Berriz, Gabriel Lowry, Patricia A. Palacios, Igor F. Tasan, Murat Roth, Frederick P. Min, Jiangyong Baumgartner, Christian Keshishian, Hasmik Addona, Terri Mootha, Vamsi K. Rosenzweig, Anthony Carr, Steven A. Fifer, Michael A. Sabatine, Marc S. Gerszten, Robert E. TI Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY; NONSURGICAL SEPTAL REDUCTION; CORONARY-ARTERY-DISEASE; AMINO-ACID-METABOLISM; HEART-DISEASE; ISCHEMIA; PLASMA; REPERFUSION; DIAGNOSIS; XANTHINE AB Emerging metabolomic tools have created the opportunity to establish metabolic signatures of myocardial injury. We applied a mass spectrometry-based metabolite profiling platform to 36 patients undergoing alcohol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned myocardial infarction (PMI). Serial blood samples were obtained before and at various intervals after PMI, with patients undergoing elective diagnostic coronary angiography and patients with spontaneous myocardial infarction (SMI) serving as negative and positive controls, respectively. We identified changes in circulating levels of metabolites participating in pyrimidine metabolism, the tricarboxylic acid cycle and its upstream contributors, and the pentose phosphate pathway. Alterations in levels of multiple metabolites were detected as early as 10 minutes after PMI in an initial derivation group and were validated in a second, independent group of PMI patients. A PMI-derived metabolic signature consisting of aconitic acid, hypoxanthine, trimethylamine N-oxide, and threonine differentiated patients with SMI from those undergoing diagnostic coronary angiography with high accuracy, and coronary sinus sampling distinguished cardiac-derived from peripheral metabolic changes. Our results identify a role for metabolic profiling in the early detection of myocardial injury and suggest that similar approaches may be used for detection or prediction of other disease states. C1 [Lewis, Gregory D.; Liu, Emerson; Martinovic, Maryann; Farrell, Laurie; Asnani, Aarti; Lowry, Patricia A.; Palacios, Igor F.; Fifer, Michael A.; Sabatine, Marc S.; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lewis, Gregory D.; Liu, Emerson; Shi, Xu; Asnani, Aarti; Cyrille, Marcoli; Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Lewis, Gregory D.; Liu, Emerson; Sabatine, Marc S.; Gerszten, Robert E.] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA USA. [Lewis, Gregory D.; Wei, Ru; Yang, Elaine; Asnani, Aarti; Ramanathan, Arvind; Shaham, Oded; Keshishian, Hasmik; Addona, Terri; Mootha, Vamsi K.; Carr, Steven A.; Gerszten, Robert E.] MIT & Harvard, Broad Inst, Cambridge, MA USA. [Shaham, Oded; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Berriz, Gabriel; Tasan, Murat; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Min, Jiangyong; Rosenzweig, Anthony] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [Baumgartner, Christian] Univ Hlth Sci Med Informat & Technol UMIT, Res Grp Clin Bioinformat, Tyrol, Austria. [Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Div Cardiol, Room 8307,149 13th St, Charlestown, MA 02129 USA. EM rgerszten@partners.org RI Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X FU NIH [R01 HL072872, U01HL083141, R01DK081572, HG003224, HG0017115, NS054052, HG004233]; Donald W. Reynolds Foundation; Fondation Leducq; Heart Failure Society of America; American Heart Association Fellow-to-Faculty Award; Harvard/MIT Clinical Investigator Training Program; Broad Institute Scientific Planning and Allocation of Resources Committee; Sarnoff Cardiovascular Research Foundation; National Human Genome Research Institute; Keck Foundation FX The authors gratefully acknowledge support from the NIH (grants R01 HL072872 to R.E. Gerszten and M.S. Sabatine; U01HL083141 to R.E. Gerszten, M.S. Sabatine, and F.P. Roth; and R01DK081572 to R.E. Gerszten), the Donald W. Reynolds Foundation (to R.E. Gerszten and M.S. Sabatine), Fondation Leducq (to A. Rosenzweig and R.E. Gerszten), Heart Failure Society of America (to G.D. Lewis), an American Heart Association Fellow-to-Faculty Award (to G.D. Lewis), the Harvard/MIT Clinical Investigator Training Program (to G.D. Lewis), and the Broad Institute Scientific Planning and Allocation of Resources Committee to establish the metabolomics platform. A. Asnani was supported by a predoctoral award from the Sarnoff Cardiovascular Research Foundation. F.P. Roth was also supported in part by National Human Genome Research Institute, NIH, grants HG003224, HG0017115, NS054052, and HG004233 and by the Keck Foundation. NR 47 TC 128 Z9 133 U1 0 U2 25 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2008 VL 118 IS 10 BP 3503 EP 3512 DI 10.1172/JCI35111 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 357EH UT WOS:000259828600031 PM 18769631 ER PT J AU Neubauer, A Maharry, K Mrozek, K Thiede, C Marcucci, G Paschka, P Mayer, RJ Larson, RA Liu, ET Bloomfield, CD AF Neubauer, Andreas Maharry, Kati Mrozek, Krzysztof Thiede, Christian Marcucci, Guido Paschka, Peter Mayer, Robert J. Larson, Richard A. Liu, Edison T. Bloomfield, Clara D. TI Patients with acute myeloid leukemia and RAS mutations benefit most from postremission high-dose cytarabine: A Cancer and Leukemia Group B study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID ACUTE-MYELOGENOUS-LEUKEMIA; N-RAS; PROGNOSTIC-SIGNIFICANCE; REPETITIVE CYCLES; POOR-PROGNOSIS; COMPETING RISK; DNA-DAMAGE; K-RAS; GENE; FLT3 AB Purpose RAS mutations occur in 12% to 27% of patients with acute myeloid leukemia (AML) and enhance sensitivity to cytarabine in vitro. We examined whether RAS mutations impact response to cytarabine in vivo. Patients and Methods One hundred eighty-five patients with AML achieving complete remission on Cancer and Leukemia Group B study 8525 and randomly assigned to one of three doses of cytarabine postremission were screened for RAS mutations. We assessed the impact of cytarabine dose on cumulative incidence of relapse (CIR) of patients with (mutRAS) and without (wild-type; wtRAS) RAS mutations. Results Thirty-four patients (18%) had RAS mutations. With 12.9 years median follow-up, the 10-year CIR was similar for mutRAS and wtRAS patients (65% v 73%; P = .31). However, mutRAS patients receiving high-dose cytarabine consolidation (HDAC; 3 g/m(2) every 12 hours on days 1, 3, and 5 or 400 mg/m(2)/d X 5 days) had the lowest 10-year CIR, 45%, compared with 68% for wtRAS patients receiving HDAC and 80% and 100%, respectively, for wtRAS and mutRAS patients receiving low-dose cytarabine (LDAC; 100 mg/m(2)/d X 5 days; overall comparison, P < .001). Multivariable analysis revealed an interaction of cytarabine dose and RAS status (P = .06). After adjusting for this interaction and cytogenetics (core binding factor [CBF] AML v non-CBF AML), wtRAS patients receiving HDAC had lower relapse risk than wtRAS patients receiving LDAC (hazard ratio [HR] = 0.67; P = .04); however, mutRAS patients receiving HDAC had greater reduction in relapse risk (HR = 0.28; P = .002) compared with mutRAS patients treated with LDAC. Conclusion AML patients carrying mutRAS benefit from higher cytarabine doses more than wtRAS patients. This seems to be the first example of an activating oncogene mutation favorably modifying response to higher drug doses in AML. C1 Univ Marburg, Div Hematol & Oncol, Marburg, Germany. Carl Gustav Carus Tech Univ, Univ Klinikum, Med Klin & Poliklin 1, Dresden, Germany. Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Chicago, IL 60637 USA. Genome Inst Singapore, Singapore, Singapore. RP Bloomfield, CD (reprint author), Ohio State Univ, Div Hematol & Oncol, Ctr Comprehens Canc, Dept Internal Med, 519 James Canc Hosp,300 W 10th Ave, Columbus, OH 43210 USA. EM Clara.Bloomfield@osumc.edu RI Liu, Edison/C-4141-2008; Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA77658, CA101140, CA114725, CA16058, CA31946] NR 36 TC 76 Z9 77 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2008 VL 26 IS 28 BP 4603 EP 4609 DI 10.1200/JCO.2007.14.0418 PG 7 WC Oncology SC Oncology GA 354OG UT WOS:000259648300016 PM 18559876 ER PT J AU Bilimoria, KY Bentrem, DJ Feinglass, JM Stewart, AK Winchester, DP Talamonti, MS Ko, CY AF Bilimoria, Karl Y. Bentrem, David J. Feinglass, Joseph M. Stewart, Andrew K. Winchester, David P. Talamonti, Mark S. Ko, Clifford Y. TI Directing surgical quality improvement initiatives: Comparison of perioperative mortality and long-term survival for cancer surgery SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol ID SEGMENTAL COLON RESECTION; HIGH-RISK SURGERY; HOSPITAL VOLUME; OPERATIVE MORTALITY; PATIENT OUTCOMES; UNITED-STATES; CAROTID-ENDARTERECTOMY; CLINICAL PATHWAY; DATA-BASE; CARE AB Purpose Quality-improvement initiatives are being developed to decrease volume-based variability in surgical outcomes. Resources for national and hospital quality-improvement initiatives are limited. It is unclear whether quality initiatives in surgical oncology should focus on factors affecting perioperative mortality or long-term survival. Our objective was to determine whether differences in hospital surgical volume have a larger effect on perioperative mortality or long-term survival using two methods. Patients and Methods From the National Cancer Data Base, 243,103 patients who underwent surgery for nonmetastatic colon, esophageal, gastric, liver, lung, pancreatic, or rectal cancer were identified. Multivariable modeling was used to evaluate 60-day mortality and 5-year conditional survival (excluding perioperative deaths) across hospital volume strata. The number of potentially avoidable perioperative and long-term deaths were calculated if outcomes at low-volume hospitals were improved to those of the highest-volume hospitals. Results Risk-adjusted perioperative mortality and long-term conditional survival worsened as hospital surgical volume decreased for all cancer sites, except for liver resections where there was no difference in survival. When comparing low-with high-volume hospitals, the hazard ratios for perioperative mortality were substantially larger than for long-term survival. However, the number of potentially avoidable deaths each year in the United States, if outcomes at low-volume hospitals were improved to the level of highest-volume centers, was significantly larger for long-term survival. Conclusion Although the magnitude of the hazard ratios implies that quality-improvement efforts should focus on perioperative mortality, a larger number of deaths could be avoided by focusing quality initiatives on factors associated with long-term survival. C1 Northwestern Univ, Dept Surg, Div Gen Internal Med, Feinberg Sch Med, Evanston, IL 60208 USA. [Bilimoria, Karl Y.] Amer Coll Surg, Canc Programs, Chicago, IL 60611 USA. Evanston NW Healthcare, Dept Surg, Evanston, IL USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Canc Programs, 633 N St Clair St,25th Floor, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu NR 60 TC 78 Z9 79 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2008 VL 26 IS 28 BP 4626 EP 4633 DI 10.1200/JCO.2007.15.6356 PG 8 WC Oncology SC Oncology GA 354OG UT WOS:000259648300019 PM 18574159 ER PT J AU Raymond, E Brandes, AA Dittrich, C Fumoleau, P Coudert, B Clement, PMJ Frenay, M Rampling, R Stupp, R Kros, JM Heinrich, MC Gorlia, T Lacombe, D van den Bent, MJ AF Raymond, Eric Brandes, Alba A. Dittrich, Christian Fumoleau, Pierre Coudert, Bruno Clement, Paul M. J. Frenay, Marc Rampling, Roy Stupp, Roger Kros, Johan M. Heinrich, Michael C. Gorlia, Thierry Lacombe, Denis van den Bent, Martin J. TI Phase II study of imatinib in patients with recurrent gliomas of various histologies: A European organisation for research and treatment of cancer brain tumor group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR; GLIOBLASTOMA-MULTIFORME; MALIGNANT GLIOMAS; TYROSINE KINASE; PROGENITOR-CELL; RECEPTOR EXPRESSION; CLINICAL-TRIALS; OLIGODENDROGLIOMAS; ASSOCIATION; PHARMACOKINETICS AB Purpose To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas. Patients and Methods This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging. Three different histologic groups were studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD), and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of 600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design was one-stage Fleming; both an objective response and 6 months of progression-free survival (PFS) were considered a successful outcome to treatment. Results A total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients with OD) were enrolled. Imatinib was in general well tolerated. The median number of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial response, including three patients with GBM; all had 6 months of PFS. The 6-month PFS rate was 16% (95% CI, 8.0% to 34.0%) in GBM, 4.0% (95% CI, 0.3% to 15.0%) in OD, and 9% (95% CI, 2.0% to 25.0%) in A. The exposure to imatinib was significantly lower in patients using enzyme-inducing antiepileptic drugs. The presence of ABCG2 point mutations were not correlated with pharmacokinetic findings. No somatic activating mutations of KIT or platelet-derived growth factor receptor -A or -B were found. Conclusion In the dose range of 600 to 1,000 mg/d, single-agent imatinib is well tolerated but has limited antitumor activity in patients with recurrent gliomas. C1 Beaujon Univ Hosp, Serv Inter Hosp Cancerol, Clichy, France. Ctr Georges Francois Leclerc, Dijon, France. Ctr Antoine Lacassagne, F-06054 Nice, France. Bellaria & Maggiore Hosp, Azienda Unita Sanitaria Locale Bologna, Bologna, Italy. Kaiser Franz Josef Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium. European Org Res & Treatment Canc Data Ctr, Brussels, Belgium. Beatson W Scotland Canc Ctr, Glasgow, Lanark, Scotland. Univ Hosp, Multidisciplinary Oncol Ctr, Lausanne, Switzerland. Univ Lausanne, Lausanne, Switzerland. [van den Bent, Martin J.] Erasmus Univ Hosp, Dr Daniel Den Hoed Canc Ctr, Neurooncol Unit, NL-3008 AE Rotterdam, Netherlands. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. RP van den Bent, MJ (reprint author), Erasmus Univ Hosp, Dr Daniel Den Hoed Canc Ctr, Neurooncol Unit, POB 5201, NL-3008 AE Rotterdam, Netherlands. EM m.vandenbent@erasmusmc.nl OI Brandes, Alba/0000-0002-2503-9089 FU European Organisation for Research and Treatment of Cancer Charitable Trust [5U10 CA11488-32]; National Cancer Institute (Bethesda, MD) [5U10 CA11488-34] FX Supported by the European Organisation for Research and Treatment of Cancer Charitable Trust and Grants No. 5U10 CA11488-32 through 5U10 CA11488-34 from the National Cancer Institute (Bethesda, MD). Additional funding was provided by Novartis Pharma AG and a Veterans Affairs Merit Review Grant (M. C. H.). The imatinib used in this study was provided free of charge by Novartis Pharma AG. NR 32 TC 125 Z9 125 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2008 VL 26 IS 28 BP 4659 EP 4665 DI 10.1200/JCO.2008.16.9235 PG 7 WC Oncology SC Oncology GA 354OG UT WOS:000259648300024 PM 18824712 ER PT J AU Schneider, BP Wang, M Radovich, M Sledge, GW Badve, S Thor, A Flockhart, DA Hancock, B Davidson, N Gralow, J Dickler, M Perez, EA Cobleigh, M Shenkier, T Edgerton, S Miller, KD AF Schneider, Bryan P. Wang, Molin Radovich, Milan Sledge, George W. Badve, Sunil Thor, Ann Flockhart, David A. Hancock, Bradley Davidson, Nancy Gralow, Julie Dickler, Maura Perez, Edith A. Cobleigh, Melody Shenkier, Tamara Edgerton, Susan Miller, Kathy D. TI Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; PROLIFERATIVE DIABETIC-RETINOPATHY; METASTATIC COLORECTAL-CANCER; GASTRIC-CANCER; VEGF GENE; OVARIAN-CANCER; PROGNOSIS; THERAPY; ANGIOGENESIS; SUNITINIB AB Purpose No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor ( VEGF) genetic variability has been associated with altered risk of breast cancer and variable promoter activity. Therefore, we evaluated the association of VEGF genotype with efficacy and toxicity in E2100, a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer. Patients and Methods DNA was extracted from tumor blocks of patients from E2100. Three hundred sixty-three samples were available to evaluate associations between genotype and outcome. Genotyping was performed for selected polymorphisms in VEGF and VEGF receptor 2. Testing for associations between each polymorphism and efficacy and toxicity was performed. Results The VEGF-2578 AA genotype was associated with a superior median overall survival ( OS) in the combination arm when compared with the alternate genotypes combined ( hazard ratio = 0.58; 95% CI, 0.36 to 0.93; P = .023). The VEGF-1154 A allele also demonstrated a superior median OS with an additive effect of each active allele in the combination arm but not the control arm ( hazard ratio = 0.62; 95% CI, 0.46 to 0.83; P = . 001). Two additional genotypes, VEGF-634 CC and VEGF-1498 TT, were associated with significantly less grade 3 or 4 hypertension in the combination arm when compared with the alternate genotypes combined ( P = .005 and P = .022, respectively). Conclusion Our data support an association between VEGF genotype and median OS as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer. C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Johns Hopkins Sidney Kimmel Canc Ctr, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Jacksonville, FL 32224 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. RP Schneider, BP (reprint author), Indiana Canc Pavil,535 Barnhill Dr,Rm 473, Indianapolis, IN 46202 USA. EM bpschnei@iupui.edu FU American Society of Clinical Oncology; Breast Cancer Research Foundation; Genentech; National Institute of General Medical Sciences Pharmacogenetics Research Network [U01GM061373] FX Supported by an American Society of Clinical Oncology Career Development Award, the Breast Cancer Research Foundation, and a grant from Genentech; also supported by funding for the Consortium on Breast Cancer Pharmacogenomics from the National Institute of General Medical Sciences Pharmacogenetics Research Network ( Grant No. U01GM061373; D. A. F.). NR 55 TC 417 Z9 424 U1 0 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2008 VL 26 IS 28 BP 4672 EP 4678 DI 10.1200/JCO.2008.16.1612 PG 7 WC Oncology SC Oncology GA 354OG UT WOS:000259648300026 PM 18824714 ER PT J AU Gelenberg, AJ Thase, ME Meyer, RE Goodwin, FK Katz, MM Kraemer, HC Potter, WZ Shelton, RC Fava, M Khan, A Trivedi, MH Ninan, PT Mann, JJ Bergeson, S Endicott, J Kocsis, JH Leon, AC Manji, HK Rosenbaum, JF AF Gelenberg, Alan J. Thase, Michael E. Meyer, Roger E. Goodwin, Frederick K. Katz, Martin M. Kraemer, Helena Chmura Potter, William Z. Shelton, Richard C. Fava, Maurizio Khan, Arif Trivedi, Madhukar H. Ninan, Philip T. Mann, John J. Bergeson, Susan Endicott, Jean Kocsis, James H. Leon, Andrew C. Manji, Husseini K. Rosenbaum, Jerrold F. TI The History and Current State of Antidepressant Clinical Trial Design: A Call to Action for Proof-of-Concept Studies SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Advancing Signal Strength in Proof of Concept Studies in Major Depression CY JUN 21-22, 2007 CL Bethesda, MD SP Univ Arizona, Dept Psychiat, Best Practice Project Management ID MAJOR DEPRESSIVE DISORDER; SEROTONIN REUPTAKE INHIBITORS; RESISTANT RECURRENT DEPRESSION; ANXIOLYTIC-LIKE ACTIVITY; MEASUREMENT-BASED CARE; HAMILTON RATING-SCALE; ASTERISK-D; ANGER ATTACKS; DRUG RESPONSE; PLACEBO-RESPONSE AB Background: The development of new antidepressant drugs has reached a plateau. There is an unmet need for faster, better, and safer medications, but as placebo-response rates rise, effect sizes shrink, and more studies fail or are negative, pharmaceutical companies are increasingly reluctant to invest in new drug development because of the risk of failure. In the absence of an identifiable human pathophysiology that can be modeled in preclinical studies, the principal point of leverage to move beyond the present dilemma may be improving the information gleaned from well-designed proof-of-concept (POC) studies of new antidepressant drugs with novel central nervous system effects. With this in mind, a group of experts was convened under the auspices of the University of Arizona Department of Psychiatry and Best Practice Project Management, Inc. Participants: Forty-five experts in the study of antidepressant drugs from academia, government (U.S. Food and Drug Administration and National Institute of Mental Health), and industry participated. Evidence/Consensus Process: In order to define the state of clinical trials methodology in the antidepressant area, and to chart a way forward, a 2-day consensus conference was held June 21-22, 2007, in Bethesda, Md., at which careful reviews of the literature were presented for discussion. Following the presentations, participants were divided into 3 workgroups and asked to address a series of separate questions related to methodology in POC studies. The goals were to review the history of antidepressant drug trials, discuss ways to improve study design and data analysis, and plan more informative POC studies. Conclusions: The participants concluded that the federal govemment, academic centers, and the pharmaceutical industry need to collaborate on establishing a network of sites at which small, POC studies can be conducted and resulting data can be shared. New technologies to analyze and measure the major affective, cognitive, and behavioral components of depression in relationship to potential biomarkers of response should be incorporated. Standard assessment instruments should be employed across studies to allow for future meta-analyses, but new instruments should be developed to differentiate subtypes and symptom clusters within the disorder that might respond differently to treatment. Better early-stage POC studies are needed and should be able to amplify the signal strength of drug efficacy and enhance the quality of information in clinical trials of new medications with novel pharmacologic profiles. (J Clin Psychiatry 2008;69:1513-1528) C1 [Gelenberg, Alan J.] Healthcare Technol Syst, Madison, WI 53717 USA. [Thase, Michael E.] Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Meyer, Roger E.] Best Practice Project Management Inc, Bethesda, MD USA. [Goodwin, Frederick K.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Katz, Martin M.] Univ Texas San Antonio, San Antonio, TX USA. [Kraemer, Helena Chmura] Stanford Univ, Palo Alto, CA 94304 USA. [Potter, William Z.] Merck & Co Inc, N Wales, PA USA. [Shelton, Richard C.] Vanderbilt Univ, Med Ctr, Mood Disorders Res Grp, Dept Psychiat, Nashville, TN USA. [Fava, Maurizio; Rosenbaum, Jerrold F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Khan, Arif] NW Clin Res Ctr, Bellevue, WA USA. [Khan, Arif] Duke Univ, Med Ctr, Durham, NC USA. [Trivedi, Madhukar H.] Univ Texas SW, Sch Med, Dallas, TX USA. [Ninan, Philip T.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Ninan, Philip T.] Wyeth Pharmaceut, Collegeville, PA USA. [Mann, John J.] New York State Psychiat Inst & Hosp, Dept Neurosci, New York, NY 10032 USA. [Bergeson, Susan] Depress & Bipolar Support Alliance, Chicago, IL USA. [Kocsis, James H.; Leon, Andrew C.] Cornell Univ, Dept Psychiat, Weill Med Coll, New York, NY 10021 USA. [Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RP Gelenberg, AJ (reprint author), Healthcare Technol Syst, 7617 Mineral Point Rd,Suite 300, Madison, WI 53717 USA. EM agelenberg@Healthtechsys.com NR 107 TC 55 Z9 56 U1 2 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2008 VL 69 IS 10 BP 1513 EP + PG 16 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 364CD UT WOS:000260312900001 PM 19192434 ER PT J AU Theoharides, TC Doyle, R AF Theoharides, Theoharis C. Doyle, Robert TI Autism, gut-blood-brain barrier, and mast cells SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material ID CORTICOTROPIN-RELEASING-HORMONE; PERVASIVE DEVELOPMENTAL DISORDERS; INFLAMMATORY-BOWEL-DISEASE; ENDOTHELIAL GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; GASTROINTESTINAL SYMPTOMS; VASCULAR-PERMEABILITY; DIFFERENTIAL RELEASE; SPECTRUM DISORDERS; OXIDATIVE STRESS C1 [Theoharides, Theoharis C.] Tufts Univ, Lab Mol Immunopharmacol & Drug Discovery, Dept Pharmacol & Expt Therapeut, Tufts Med Ctr,Sch Med, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Dept Internal Med, Tufts Med Ctr, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Dept Biochem, Tufts Med Ctr, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Dept Psychiat, Tufts Med Ctr, Boston, MA 02111 USA. [Doyle, Robert] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Psychopharmacol, Boston, MA USA. RP Theoharides, TC (reprint author), Tufts Univ, Lab Mol Immunopharmacol & Drug Discovery, Dept Pharmacol & Expt Therapeut, Tufts Med Ctr,Sch Med, 136 Harrison Ave, Boston, MA 02111 USA. EM theoharis.theoharides@tufts.edu FU NIAMS NIH HHS [AR47652]; NINDS NIH HHS [NS38326] NR 95 TC 21 Z9 22 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2008 VL 28 IS 5 BP 479 EP 483 DI 10.1097/JCP.0b013e3181845f48 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 351MH UT WOS:000259427900001 PM 18794641 ER PT J AU Rudolph, JL Gardner, KF Gramigna, GD McGlinchey, RE AF Rudolph, James L. Gardner, Kelly F. Gramigna, Gan D. McGlinchey, Regina E. TI Antipsychotics and oropharyngeal dysphagia in hospitalized older patients SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID ATYPICAL ANTIPSYCHOTICS; ASPIRATION PNEUMONIA; ACUTE STROKE; RISK; DEATH AB In the inpatient setting, dysphagia is a common, morbid, and costly condition. Antipsychotic medications in older patients have been associated with dysphagia. The purpose of this study was to determine if hospitalized patients who were exposed to antipsychotic medications had worse swallowing function than those who were not exposed. Retrospectively, all patients referred for swallowing difficulty who underwent a videofluoroscopic swallowing study during the course of their hospital care were considered eligible. We excluded patients younger than 50 years and those with a history of dysphagia, a medical cause for dysphagia, or chronic antipsychotic medication usage. Patients exposed to antipsychotics (n = 17) were matched at a 3:1 ratio to patients without exposure (n = 51) for age, comorbidity, and anticholinergic risk. Videofluoroscopic swallowing study was scored according to the Dysphagia Severity Rating Scale (range, 0-6; 6 = worst). Patients who were given antipsychotic medications scored significantly worse on the Dysphagia Severity Rating Scale compared with matched controls (4.1 +/- 1.0 vs 3.0 +/- 1.4; P < 0.01). Using the medication and dosage, the antipsychotic exposure was quantified by converting to chlorpromazine equivalency units. Higher doses of antipsychotic medication were associated with worse swallowing function (P = 0.04). Thus, the potential impact on swallow functions Should be considered when prescribing antipsychotic medications in older patients. C1 [Rudolph, James L.] VA Boston Healthcare Syst GRECC, Boston, MA 02130 USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Rudolph, James L.; McGlinchey, Regina E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gardner, Kelly F.; Gramigna, Gan D.] VA Boston Healthcare Syst, Dept Speech Pathol & Audiol, Boston, MA 02130 USA. RP Rudolph, JL (reprint author), VA Boston Healthcare Syst GRECC, JP-182,150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org RI McGlinchey, Regina/R-1971-2016 FU VA Rehabilitation Research Career Development Award; VA Merit Review; NIAAA [R01 1405] FX Dr Rudolph is supported by a VA Rehabilitation Research Career Development Award. Dr McGlinchey is Supported by a VA Merit Review and NIAAA R01 1405. NR 23 TC 17 Z9 17 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2008 VL 28 IS 5 BP 532 EP 535 DI 10.1097/JCP.0b013c318184c905 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 351MH UT WOS:000259427900009 PM 18794648 ER PT J AU Bartlett, BL Tyring, SK Fife, K Gnann, JW Hadala, JT Kianifard, F Berber, E AF Bartlett, Brenda L. Tyring, Stephen K. Fife, Kenneth Gnann, John W., Jr. Hadala, Joseph T. Kianifard, Farid Berber, Erhan TI Famciclovir treatment options for patients with frequent outbreaks of recurrent genital herpes: The RELIEF trial SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE Famciclovir; Genital herpes; Recurrent; Herpes simplex virus ID PLACEBO-CONTROLLED TRIAL; SIMPLEX-VIRUS-INFECTION; DAILY ORAL FAMCICLOVIR; DOUBLE-BLIND; THERAPY; SUPPRESSION; PREVENTION; ACYCLOVIR; VALACYCLOVIR; MULTICENTER AB Background: Recurrent genital HSV outbreaks are common among those suffering from the disease. Antiviral medications taken as suppressive therapy can reduce the frequency of these recurrences and reduce viral shedding occurring in between recurrences. Objectives: To investigate the efficacy and safety of oral famciclovir as episodic (125 mg twice daily for 5 days) and suppressive (250 mg twice daily) treatment of recurrent genital herpes (RGH). Study design: This was a randomized, multicenter, 6-month, open-label study. Efficacy variables were time to first recurrence of RGH symptoms, and change in total score of the Recurrent Genital Herpes Quality of Life (RGHQoL) questionnaire. Subject satisfaction questions were summarized. Results: 384 subjects were randomized. There was a highly statistically significant difference between treatments in time to first recurrence of symptoms in favor of suppressive treatment (p < 0.0001). There was no significant difference between treatments in total score of the RGHQoL or in subject satisfaction with treatment. Conclusions: This study demonstrated that, compared to episodic treatment, suppressive treatment with oral famciclovir may extend the time to symptomatic outbreaks in patients with frequent recurrences of genital herpes. (C) 2008 Elsevier B.V. All rights reserved. C1 [Bartlett, Brenda L.; Tyring, Stephen K.] Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA. [Fife, Kenneth] Indiana Univ, Sch Med, Indianapolis, IN USA. [Gnann, John W., Jr.] Univ Alabama, Birmingham, AL USA. [Gnann, John W., Jr.] Birmingham VA Med Ctr, Birmingham, AL USA. [Hadala, Joseph T.; Kianifard, Farid; Berber, Erhan] Novartis Pharmaceut Corp, E Hanover, NJ 07936 USA. RP Tyring, SK (reprint author), Ctr Clin Studies, 2060 Space Pk Dr, Houston, TX 77058 USA. EM bbartlett@ccstexas.com; styring@ccstexas.com; kfife@iupui.edu; jgnann@uab.edu; joseph.hadala@novartis.com; farid.kianifard@novartis.com; erhan.berber@novartis.com FU Novartis; Antigenics, Astellas, GlaxoSmithKline, Merck, and Novartis; Astellas, Merck, and Novartis FX Liptak and Mark J. Fedele of Novartis Pharmaceuticals Corporation for writing and editorial assistance. ST has received research grants from Novartis and has participated in Novartis' advisory boards and speakers' bureau. KF has received research grants from Antigenics, Astellas, GlaxoSmithKline, Merck, and Novartis, has consulted for GlaxoSmithKline, and received speaking fees from Merck. GWG has received research funding from Astellas, Merck, and Novartis, has consulted for Merck and ViroPharma and has received speaking fees from GlaxoSmithKline and Merck. JTH, KF, and EB are employees of Novartis Pharmaceuticals Corporation and are eligible for Novartis stock and stock options. NR 28 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD OCT PY 2008 VL 43 IS 2 BP 190 EP 195 DI 10.1016/j.jcv.2008.06.004 PG 6 WC Virology SC Virology GA 360QF UT WOS:000260071700011 PM 18621575 ER PT J AU Jensen, SL McCuaig, C Zembowicz, A Hurt, MA AF Jensen, Sarah L. McCuaig, Catherine Zembowicz, Artur Hurt, Mark A. TI Bullous lesions in acrodermatitis enteropathica delaying diagnosis of zinc deficiency: a report of two cases and review of the literature SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID DIODOQUIN AB Acrodermatitis enteropathica (AE) is a rare disorder associated with poor absorption of Zinc. A variety of clinical and histological findings have been reported in the literature, described mainly in isolated case reports. Because of the varied nature of these cases, the histological features of AE are described often as non-specific. We describe lesions of Ae in two patients who presented with vesiculobullous and erosive skin lesions, both showing intra-epidermal, inflammatory vesiculation with surrounding eosinophilic epidermis and necrotic keratinocytes. The lack of clinical suspicion of AE led to their misdiagnosis. We present these two patients to further characterize the bullous variant of AE, and we review the previously reported clinical and histopathological findings. C1 [Jensen, Sarah L.] St Louis Univ Hosp, Dept Dermatol, St Louis, MO USA. [McCuaig, Catherine] Univ Montreal, Hop St Justine, Montreal, PQ, Canada. [Zembowicz, Artur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zembowicz, Artur] Lahey Clin Fdn, Burlington, MA USA. [Zembowicz, Artur] Harvard Vangard Med Associates, Boston, MA USA. [Hurt, Mark A.] WCP Lab, Maryland Hts, MO USA. RP Jensen, SL (reprint author), St Louis Univ, Dept Dermatol, 1402 S Grand, St Louis, MO 63104 USA. EM sarahljensen@gmail.com NR 41 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD OCT PY 2008 VL 35 SU 1 BP 1 EP 13 DI 10.1111/j.1600-0560.2008.00981.x PG 13 WC Dermatology; Pathology SC Dermatology; Pathology GA 358EW UT WOS:000259900900001 PM 18537855 ER PT J AU Davis, TL Mandal, RV Bevona, C Tsai, KY Moschella, SL Staszewski, R Zembowicz, A AF Davis, Tracy L. Mandal, Rajni V. Bevona, Caroline Tsai, Kenneth Y. Moschella, Samuel L. Staszewski, Robert Zembowicz, Artur TI Collagenous vasculopathy: a report of three cases SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID ULTRASTRUCTURE AB Cutaneous collagenous vasculopathy (CCV) is an idiopathic microangiopathy involving the superficial blood vessels that was initially reported in a 54-year-old male. We recently have identified this rarely reported entity in three Caucasian males. The first patient was a 59-year-old male with diabetes, hypertension and hypercholesterolemia who presented with multiple, red, blanchable, asymptomatic telangiectasias covering the extensor surface of the forearms, the lower abdomen and parts of the chest. The second patient was a 62-year-old male with psoriasis and extensive arthritis who presented with prominent telangiectasias on the left lateral distal thigh with mild overlying epidermal atrophy. The third patient was an 80-year-old male with atrial fibrillation who presented with blanching, telangiectatic areas on the abdomen, thighs and back. Histologically, the skin lesions showed ectatic superficial small blood vessels with laminated, hyalinized concretions around vessels that were highlighted with periodic acid-Schiff staining following diastase digestion and reactive by immunohistochemical staining with an antibody to collagen type IV. CCV is a rare and poorly understood entity with distinct histopathological features that may clinically resemble generalized essential telangiectasia (GET), yet which may affect a different demographic population than GET. Awareness of this uncommon entity may further help to elucidate its etiology. C1 [Davis, Tracy L.] Diagnost Pathol Med Grp Inc, Sacramento, CA USA. [Mandal, Rajni V.; Zembowicz, Artur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Bevona, Caroline; Moschella, Samuel L.; Zembowicz, Artur] Lahey Clin Fdn, Med Ctr, Dept Dermatol, Burlington, MA USA. [Tsai, Kenneth Y.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Dermatopathol,Massachusetts Gen Hosp, Boston, MA 02215 USA. [Staszewski, Robert] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Zembowicz, A (reprint author), Lahey Clin Fdn, Dept Pathol, Clin 41 Mall Rd, Burlington, MA 01805 USA. EM dr.z.@dermatopathologyconsultations.com NR 4 TC 18 Z9 18 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD OCT PY 2008 VL 35 IS 10 BP 967 EP 970 DI 10.1111/j.1600-0560.2007.00930.x PG 4 WC Dermatology; Pathology SC Dermatology; Pathology GA 347MZ UT WOS:000259147000014 PM 18537865 ER PT J AU Peak, DA Brown, DFM Nadel, ES AF Peak, David A. Brown, David F. M. Nadel, Eric S. TI FEVER, HEADACHE, AND PROPTOSIS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID VENOUS SINUS THROMBOSIS; SEPTIC THROMBOSIS C1 [Peak, David A.; Brown, David F. M.; Nadel, Eric S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Peak, David A.; Brown, David F. M.; Nadel, Eric S.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders 114,55 Fruit St, Boston, MA 02114 USA. NR 16 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2008 VL 35 IS 3 BP 301 EP 304 DI 10.1016/j.jemermed.2008.08.001 PG 4 WC Emergency Medicine SC Emergency Medicine GA 358VM UT WOS:000259945600014 PM 18762402 ER PT J AU Eisner, BH Iqbal, A Namasivayam, S Catalano, O Kambadakone, A Dretler, SP Sahani, DV AF Eisner, Brian H. Iqbal, Ahsan Namasivayam, Saravanan Catalano, Onofrio Kambadakone, Avinash Dretler, Stephen P. Sahani, Dushyant V. TI Differences in Computed Tomography Density of the Renal Papillae of Stone Formers and Non-Stone-Formers: A Pilot Study SO JOURNAL OF ENDOUROLOGY LA English DT Article; Proceedings Paper CT 25th World Congress of Endourology CY OCT 30-NOV 03, 2007 CL Cancun, MEXICO ID RANDALLS PLAQUE; HELICAL CT; NEPHROLITHIASIS; PATHOGENESIS; CALCULI AB Purpose: It is thought that Randall's plaques, calcium deposits in the renal papillae of patients with nephrolithiasis, may serve as a nidus for stone formation. We examined the density of renal papillae in patients with stones and control patients using attenuation measurements (HU) on Computed Tomography (CT) to determine whether nephrolithiasis is associated with radiographic changes in renal papillae. Materials and Methods: Hounsfield density measurements of a 0.2cm(2) area of the renal papillae of 17 patients with a single renal calyceal calculus and 15 age- matched control patients were performed. Measurements were done for renal papillae upper, middle, and lower pole calyces for all patients. Statistical comparisons were made using the student's t-test. Results: Patients with nephrolithiasis and control patients were similar with respect to mean age (41.2 years versus 42.2 years, p = 0.82) and baseline serum creatinine (0.86 mg/dl versus 0.93 mg/dl, p = 0.21). Mean Hounsfield density of renal papillae of stone patients in calyces with stones was significantly greater than that of location- matched papillae from control patients (54.4 versus 36.6, p < 0.0001). Mean Hounsfield density of all papillae of the affected kidney (i. e., kidney with stone) in stone patients was significantly greater than that of control patients (50.9 versus 36.4, p < 0.0001). Mean Hounsfield density of all papillae in the stone- free kidney of stone patients was significantly greater than that of control patients (50.0 versus 36.1, p < 0.0001). In stone patients, when comparing the affected kidney with the stone- free kidney, there was no difference in mean papilla Hounsfield density (50.3 versus 50.9, p = 0.59). Conclusions: Hounsfield density of the renal papilla is significantly increased in patients with nephrolithiasis when compared with age- matched controls. This is true of calyces with stones, calyces without stones in kidneys with stones, and calyces of the contralateral stone- free kidney. There is no difference in renal papilla Hounsfield density between kidneys with and without stones in patients with nephrolithiasis. In the future, this information may be useful in predicting which patients may develop nephrolithiasis. C1 [Iqbal, Ahsan; Namasivayam, Saravanan; Catalano, Onofrio; Kambadakone, Avinash; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Eisner, Brian H.; Dretler, Stephen P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 9 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD OCT PY 2008 VL 22 IS 10 BP 2207 EP 2210 DI 10.1089/end.2008.9721 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 369JN UT WOS:000260690600003 PM 18831676 ER PT J AU Chen, J Griffin, JD AF Chen, J. Griffin, J. D. TI Using a zebrafish Danio rerio model system to study NOTCH1-induced T-cell leukaemia SO JOURNAL OF FISH BIOLOGY LA English DT Review DE notch; T-ALL; zebrafish ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NOTCH SIGNAL-TRANSDUCTION; OF-DELTEX GENE; TRANSGENIC ZEBRAFISH; C-MYC; UBIQUITIN LIGASE; STRUCTURAL BASIS; ANKYRIN REPEAT; HUMAN HOMOLOG; ACTIVATION AB Notch receptors are a family of cell-surface proteins that regulate cell fate decisions and growth control. Human NOTCH1 gain-of-function mutations-deletions have been found in c. 60% of patients with T-cell acute lymphoblastic leukaemia (T-ALL). Therefore, understanding the molecular mechanisms by which dysregulated Notch-signalling induces leukaemia is of importance and may reveal novel targets for the development of more effective therapies. Zebrafish, Danio rerio, is an ideal model system to use for forward genetic screens to uncover pathways critical for transformation. Danio rerio also have the capacity for small molecule screening for drug discovery. rag2-ICN1-EGFP transgenic fish have been created that develop a T-cell leukaemia, and these fish are now being used in genetic modifier screens. (C) 2008 The Authors. C1 [Chen, J.; Griffin, J. D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM james_griffin@dfci.harvard.edu FU National Institute of Health [CA-36167] FX This review is supported by a grant from the National Institute of Health CA-36167 to J.D.G. NR 77 TC 0 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-1112 J9 J FISH BIOL JI J. Fish Biol. PD OCT PY 2008 VL 73 IS 5 BP 1121 EP 1138 DI 10.1111/j.1095-8649.2008.01979.x PG 18 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 357SA UT WOS:000259865400004 ER PT J AU Ferrone, CR Warshaw, AL Rattner, DW Berger, D Zheng, H Rawal, B Rodriguez, R Thayer, SP Fernandez-del Castillo, C AF Ferrone, Cristina R. Warshaw, Andrew L. Rattner, David W. Berger, David Zheng, Hui Rawal, Bhupendra Rodriguez, Ruben Thayer, Sarah P. Fernandez-del Castillo, Carlos TI Pancreatic fistula rates after 462 distal pancreatectomies: Staplers do not decrease fistula rates SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/109th Annual Meeting of the American-Gastroenterological-Association CY MAY 17-22, 2008 CL San Diego, CA SP Amer Gastroenterol Assoc DE distal pancreatectomy; pancreatic fistula ID RISK-FACTORS; LEAK; REINFORCEMENT; MORBIDITY; RESECTION; CLOSURE; COST AB Introduction Pancreatic fistula is a major source of morbidity after distal pancreatectomy (DP). We reviewed 462 consecutive patients undergoing DP to determine if the method of stump closure impacted fistula rates. Methods A retrospective review of clinicopatologic variables of patients who underwent DP between February 1994 and February 2008 was performed. The International Study Group classification for pancreatic fistula was utilized (Bassi et al., Surgery, 138(1):8-13, 2005). Results The overall pancreatic fistula rate was 29% (133/462). DP with splenectomy was performed in 321 (69%) patients. Additional organs were resected in 116 (25%) patients. The pancreatic stump was closed with a fish-mouth suture closure in 227, of whom 67 (30%) developed a fistula. Pancreatic duct ligation did not decrease the fistula rate (29% vs. 30%). A free falciform patch was used in 108 patients, with a fistula rate of 28% (30/108). Stapled compared to stapled with staple line reinforcement had a fistula rate of 24% (10/41) vs. 33% (15/45). There is no significant difference in the rate of fistula formation between the different stump closures (p=0.73). On multivariate analysis, BMI>30 kg/m(2), male gender, and an additional procedure were significant predictors of pancreatic fistula. Conclusions The pancreatic fistula rate was 29%. Staplers with or without staple line reinforcement do not significantly reduce fistula rates after DP. Reduction of pancreatic fistulas after DP remains an unsolved challenge. C1 [Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Zheng, Hui; Rawal, Bhupendra] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Ferrone, Cristina R.; Warshaw, Andrew L.; Rattner, David W.; Berger, David; Rodriguez, Ruben; Thayer, Sarah P.; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Massachusetts Gen Hosp, Dept Surg, Wang 460,15 Parkman St, Boston, MA 02114 USA. EM cferrone@partners.org FU NIDDK NIH HHS [K08 DK071329] NR 16 TC 108 Z9 122 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD OCT PY 2008 VL 12 IS 10 BP 1691 EP 1697 DI 10.1007/s11605-008-0636-2 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 350RT UT WOS:000259371500015 PM 18704597 ER PT J AU Sylla, P Willingham, FF Sohn, DK Gee, D Brugge, WR Rattner, DW AF Sylla, Patricia Willingham, Field F. Sohn, Dae K. Gee, Denise Brugge, William R. Rattner, David W. TI NOTES rectosigmoid resection using transanal endoscopic microsurgery (TEM) with transgastric endoscopic assistance: A pilot study in swine SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract/Digestive Disease Week CY MAY 17-21, 2008 CL San Diego, CA SP Soc Surg Alimentary Tract DE NOTES; TEM; transanal; transgastric; rectosigmoid; endoscopic ID PORCINE MODEL; NOTES SURVIVAL; DISTAL PANCREATECTOMY; ABDOMINAL EXPLORATION; SURGERY; CHOLECYSTECTOMY; PERITONEOSCOPY; FEASIBILITY; HUMANS; HERNIA AB Introduction Transanal endoscopic microsurgery (TEM) provides direct endoscopic access to the rectum and peritoneal cavity. The feasibility of natural orifice translumenal endoscopic surgery (NOTES) rectosigmoid resection using TEM was evaluated in swine. Transgastric endoscopic assistance to extend transanal colon mobilization was also investigated. Full-thickness circumferential rectal dissection was performed and extended proximally. After maximal sigmoid mobilization, the specimen was exteriorized and transected, and the proximal colon was stapled to the distal rectum. In a subset of animals, transgastric endoscopic access was used to mobilize the colon further. Results Rectosigmoid resection using TEM was performed in two non-survival and seven swine cadavers (n=9). The mean procedure time was 3 h (2.5-4 h), and mean length of resected colon was 16.7 cm (10-25 cm). Transgastric endoscopic assistance was used in three cadavers and two non-survival swine (n=5) with a mean operative time of 3.5 h (3.5-3.75 h). The mean length of colon mobilized with transgastric and transanal endoscopic access was 24.4 cm (20-27 cm) vs. 16.7 cm which mobilized the transanal approach alone (p=0.016). A posterior anastomotic defect was noted in two animals. Conclusion Transanal rectosigmoid resection with TEM is feasible in swine. Combined transgastric and TEM access is a promising new technique for NOTES colorectal resection. C1 [Sylla, Patricia; Gee, Denise; Rattner, David W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Willingham, Field F.; Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Boston, MA USA. RP Sylla, P (reprint author), 15 Parkman St,WACC 460, Boston, MA 02114 USA. EM psylla@partners.org OI Willingham, Field/0000-0002-7071-3001 NR 18 TC 70 Z9 81 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD OCT PY 2008 VL 12 IS 10 BP 1717 EP 1723 DI 10.1007/s11605-008-0637-1 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 350RT UT WOS:000259371500020 PM 18704596 ER PT J AU Kunitake, H Hodin, R Shellito, PC Sands, BE Korzenik, J Bordeianou, L AF Kunitake, Hiroko Hodin, Richard Shellito, Paul C. Sands, Bruce E. Korzenik, Joshua Bordeianou, Liliana TI Perioperative treatment with infliximab in patients with Crohn's disease and ulcerative colitis is not associated with an increased rate of postoperative complications SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE infliximab; Crohn's disease; ulcerative colitis; postoperative complications ID ANTITUMOR NECROSIS FACTOR; RHEUMATOID-ARTHRITIS; MAINTENANCE INFLIXIMAB; THERAPY; INFECTIONS; RISK; COMORBIDITY; SURGERY AB Purpose The impact of infliximab (IFX) on postoperative complications in surgical patients with Crohn's disease (CD) and ulcerative colitis (UC) is unclear. We examined a large patient cohort to clarify whether a relationship exists between IFX and postoperative complications. Methods A total of 413 consecutive patients-188 (45.5%) with suspected CD, 156 (37.8%) with UC, and 69 (16.7%) with indeterminate colitis-underwent abdominal surgery at the Massachusetts General Hospital between January 1993 and June 2007. One hundred one (24.5%) had received preoperative IFX <= 12 weeks before surgery. These patients were compared to those who did not receive IFX with respect to demographics, comorbidities, presence of preoperative infections, steroid use, and nutritional status. We then compared the cumulative rate of complications for each group, which included deaths, anastomotic leak, infection, thrombotic complications, prolonged ileus/small bowel obstruction, cardiac, and hepatorenal complications. Potential risk factors for infectious complications including preexisting infection, pathological diagnosis, and steroid or IFX exposure were further evaluated using logistic regression analysis. Results Patients were similar with respect to gender (IFX=40.6% men vs. non-IFX=51.9%, p=0.06), age (36.1 years vs.37.8, p=0.43), Charlson Comorbidity Index (5.3 vs. 5.7, p=0.25), concomitant steroids (75.3% vs. 76.9%, p=0.79), preoperative albumin level (3.3 vs. 3.2, p=0.36), and rate of emergent surgery (3.0% vs. 3.5%, p=1.00). IFX patients had higher rates of CD (56.4% vs. 41.9%, p=0.02), concomitant azathioprine/6-mercaptopurine use (34.6% vs. 16.6%, p<0.0001), and lower rates of intra-abdominal abscess (3.9% vs. 11%, p<0.05). After surgery, the two groups had similar rates of death (2% vs. 0.3% p=0.09), anastomotic leak (3.0% vs. 2.9%, p=0.97), cumulative infections (5.97% vs. 10.1%, p=1), thrombotic complications (3.6% vs. 3.0%, p=0.06), prolonged ileus/small bowel obstructions (3.9 vs. 2.8, p=0.59), cardiac complications (1% vs. 0.6%, p=0.42), and hepatic or renal complications (1.0 vs. 0.6% p=0.72). A logistic regression model was then created to assess the impact of IFX, as well as other potential risk factors, on the rates of cumulative postoperative infections. We found that steroids (odds ratio [OR]=1.2, p=0.74), IFX (OR 2.5, p=0.14), preoperative diagnosis of CD (OR=0.7, p=0.63) or UC (OR=0.6, p=0.48), and preoperative infection (OR=1.2, p=0.76) did not affect rates of clinically important postoperative infections. Conclusions Preoperative IFX was not associated with an increased rate of cumulative postoperative complications. C1 [Kunitake, Hiroko; Hodin, Richard; Shellito, Paul C.; Sands, Bruce E.; Korzenik, Joshua; Bordeianou, Liliana] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kunitake, Hiroko; Hodin, Richard; Shellito, Paul C.; Sands, Bruce E.; Korzenik, Joshua; Bordeianou, Liliana] Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. [Sands, Bruce E.; Korzenik, Joshua] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Kunitake, Hiroko; Hodin, Richard; Shellito, Paul C.; Sands, Bruce E.; Korzenik, Joshua; Bordeianou, Liliana] Harvard Univ, Sch Med, Boston, MA USA. [Kunitake, Hiroko; Hodin, Richard; Shellito, Paul C.; Bordeianou, Liliana] Massachusetts Gen Hosp, Dept Gastrointestinal Surg, Boston, MA USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@partners.org NR 19 TC 129 Z9 134 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD OCT PY 2008 VL 12 IS 10 BP 1730 EP 1736 DI 10.1007/s11605-008-0630-8 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 350RT UT WOS:000259371500022 PM 18709514 ER PT J AU Metlay, JP Hennessy, S Localio, AR Han, XY Yang, W Cohen, A Leonard, CE Haynes, K Kimmel, SE Feldman, HI Strom, BL AF Metlay, Joshua P. Hennessy, Sean Localio, A. Russell Han, Xiaoyan Yang, Wei Cohen, Abigail Leonard, Charles E. Haynes, Kevin Kimmel, Stephen E. Feldman, Harold I. Strom, Brian L. TI Patient reported receipt of medication instructions for warfarin is associated with reduced risk of serious bleeding events SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med DE anticoagulation; patient communication; medication safety ID ADVERSE DRUG EVENTS; ANTICOAGULATION-CONTROL; INDEX; CARE; COMPLICATIONS; THERAPY; HEALTH; IMPACT AB BACKGROUND: Adverse drug events are an important cause of preventable hospitalizations. OBJECTIVE: To identify whether patient report of receipt of medication instructions and markers of complex care (multiple physicians, recent hospitalization) predict the risk of serious bleeding for older adults on warfarin. DESIGN: Prospective cohort study of older adults. PARTICIPANTS: Subjects filled new or refill prescriptions for warfarin at the time of enrollment. MEASUREMENTS: Hospitalizations were identified through a state-wide registry. Discharge summaries of hospitalizations for possible warfarin related bleeding events were reviewed by trained abstractors and clinical experts. Incidence rate ratios (IRR) were estimated based on person-months of exposure using Poisson regression models. RESULTS: From March 2002 through May 2003, we enrolled a total of 2346 adults on warfarin. Over a two-year follow-up period, there were 126 hospitalizations due to warfarin-related bleeding (4.6 hospitalizations per 100 person-years of exposure). Patients who reported receiving medication instructions from either a physician or nurse plus a pharmacist had a 60% reduced rate of subsequently experiencing a serious bleeding event over the next 2 years (adjusted IRR 0.40, 95% CI 0.24-0.68). Having >= 4 physicians providing medication prescriptions over the last 3 months and filling prescriptions at > 1 pharmacy over the last 3 months were independently associated with increased bleeding rates (adjusted IRRs 2.37, 95% CI 1.22-4.57 and 1.61, 95% CI 0.97-2.67, respectively). CONCLUSIONS: The rate of warfarin-related hospitalization for bleeding is substantially lower for patients who report receiving medication instructions from a physician or nurse and a pharmacist. C1 [Metlay, Joshua P.; Hennessy, Sean; Localio, A. Russell; Han, Xiaoyan; Yang, Wei; Cohen, Abigail; Leonard, Charles E.; Haynes, Kevin; Kimmel, Stephen E.; Feldman, Harold I.; Strom, Brian L.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Metlay, Joshua P.; Hennessy, Sean; Han, Xiaoyan; Yang, Wei; Cohen, Abigail; Leonard, Charles E.; Kimmel, Stephen E.; Feldman, Harold I.; Strom, Brian L.] Univ Penn, PRIME, Philadelphia, PA 19104 USA. [Metlay, Joshua P.; Hennessy, Sean; Localio, A. Russell; Cohen, Abigail; Leonard, Charles E.; Haynes, Kevin; Kimmel, Stephen E.; Feldman, Harold I.; Strom, Brian L.] Univ Penn, CERTs, Philadelphia, PA 19104 USA. [Metlay, Joshua P.; Kimmel, Stephen E.; Feldman, Harold I.; Strom, Brian L.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Metlay, JP (reprint author), 712 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jmetlay@mail.med.upenn.edu RI Leonard, Charles/K-3447-2012; Yang, Wei/A-9223-2009; Cohen, Abigail/K-9180-2013 OI Yang, Wei/0000-0001-8984-4389; Cohen, Abigail/0000-0002-7425-7218 FU AHRQ HHS [P01 HS011530, P01-HS11530]; NHLBI NIH HHS [K24 HL070936, R01 HL066176, R01 HL076697]; NIA NIH HHS [F32 AG026180, R01 AG025152]; NIDDK NIH HHS [K24 DK002651] NR 23 TC 19 Z9 22 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2008 VL 23 IS 10 BP 1589 EP 1594 DI 10.1007/s11606-008-0708-8 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 347LD UT WOS:000259142200008 PM 18618191 ER PT J AU Pollack, CE Mallya, G Polsky, D AF Pollack, Craig Evan Mallya, Giridhar Polsky, Daniel TI The impact of consumer-directed health plans and patient socioeconomic status on physician recommendations for colorectal cancer screening SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE consumer-directed health plans; patient socioeconomic status; physician decision-making; colorectal cancer screening ID OF-POCKET COSTS; FECAL OCCULT BLOOD; PREVENTIVE SERVICES; NATIONAL-SURVEY; CARE; PARTICIPATION; COMMUNICATION; COLONOSCOPY; PERSPECTIVE; INSURANCE AB BACKGROUND: Consumer-directed health plans are increasingly common, yet little is known about their impact on physician decision-making and preventive service use. OBJECTIVE: To determine how patients' deductible levels and socioeconomic status may affect primary care physicians' recommendations for colorectal cancer screening. DESIGN, SETTING AND PARTICIPANTS: Screening recommendations were elicited using hypothetical vignettes from a national sample of 1,500 primary care physicians. Physicians were randomized to one of four vignettes describing a patient with either low or high socioeconomic status (SES) and either low- or high-deductible plan. Bivariate and multivariate analyses were used to examine how recommendations varied as a function of SES and deductible. OUTCOME MEASURES: Rates of recommendation for home fecal occult blood testing, sigmoidoscopy, colonoscopy, and inappropriate screening, defined as no screening or office-based fecal occult blood testing. RESULTS: A total of 528 (49%) eligible physicians responded. Overall, 7.2% of physicians recommended inappropriate screening; 3.2% of patients with high SES in low-deductible plans received inappropriate screening recommendations and 11.4% of patients with low SES in high-deductible plans for an adjusted odds ratio of 0.22 (0.05-0.89). The odds of a colonoscopy recommendation were over ten times higher (AOR 11.46, 5.26-24.94) for patients with high SES in low-deductible plans compared to patients with low SES in high-deductible plans. Funds in medical savings accounts eliminated differences in inappropriate screening recommendations. CONCLUSIONS: Patient SES and deductible-level affect physician recommendations for preventive care. Coverage of preventive services and funds in medical savings accounts may help to mitigate the impact of high-deductibles and SES on inappropriate recommendations. C1 [Pollack, Craig Evan; Mallya, Giridhar] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Pollack, Craig Evan; Mallya, Giridhar; Polsky, Daniel] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Pollack, Craig Evan] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Polsky, Daniel] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Polsky, Daniel] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. RP Pollack, CE (reprint author), Univ Penn, Robert Wood Johnson Clin Scholars Program, 1303B Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM craige@mail.med.upenn.edu FU Robert Wood Johnson Clinical Scholars Program at the University of Pennsylvania FX The authors wish to thank the following individuals for their helpful suggestions and advice: David Asch M. D., Judy Shea Ph. D., Katrina Armstrong M. D., and Josh Metlay M. D. Ph. D. at the University of Pennsylvania and Caleb Alexander M. D. at the University of Chicago. No compensation was received for their contributions.; Funding for the study was provided by the Robert Wood Johnson Clinical Scholars Program at the University of Pennsylvania. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and the preparation, review or approval of the manuscript. Drs. Pollack and Mallya had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. This work has been presented at the annual meetings of the Robert Wood Johnson Clinical Scholars Program (Fort Lauderdale, November 2007) and the North American Primary Care Research Group (Vancouver, October 2007); Funding for the study was provided by the Robert Wood Johnson Clinical Scholars Program at the University of Pennsylvania. NR 47 TC 7 Z9 7 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2008 VL 23 IS 10 BP 1595 EP 1601 DI 10.1007/s11606-008-0714-x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 347LD UT WOS:000259142200009 PM 18629590 ER PT J AU Lagu, T Kaufman, EJ Asch, DA Armstrong, K AF Lagu, Tara Kaufman, Elinore J. Asch, David A. Armstrong, Katrina TI Content of weblogs written by health professionals SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE weblog; professionalism; Internet ID MEDICINE; TOOL AB BACKGROUND: Medical weblogs ("blogs") have emerged as a new connection between health professionals and the public. OBJECTIVE: To examine the scope and content of medical blogs and approximate how often blog authors commented about patients, violated patient privacy, or displayed a lack of professionalism. DESIGN: We defined medical blogs as those that contain some medical content and were apparently written by physicians or nurses. We used the Google search term "medical blog" to begin a modified snowball sampling method to identify sites posting entries from 1/1/06 through 12/14/06. We reviewed five entries per blog, categorizing content and characteristics. RESULTS: We identified 271 medical blogs. Over half (56.8%) of blog authors provided sufficient information in text or image to reveal their identities. Individual patients were described in 114 (42.1%) blogs. Patients were portrayed positively in 43 blogs (15.9%) and negatively in 48 blogs (17.7%). Of blogs that described interactions with individual patients, 45 (16.6%) included sufficient information for patients to identify their doctors or themselves. Three blogs showed recognizable photographic images of patients. Healthcare products were promoted, either by images or descriptions, in 31 (11.4%) blogs. CONCLUSIONS: Blogs are a growing part of the public face of the health professions. They offer physicians and nurses the opportunity to share their narratives. They also risk revealing confidential information or, in their tone or content, risk reflecting poorly on the blog authors and their professions. The health professions should assume some responsibility for helping authors and readers negotiate these challenges. C1 [Lagu, Tara; Kaufman, Elinore J.; Armstrong, Katrina] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Lagu, Tara; Asch, David A.; Armstrong, Katrina] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Lagu, T (reprint author), Univ Penn, Robert Wood Johnson Clin Scholars Program, 423 Guardian Dr,13th Floor Blockley, Philadelphia, PA 19104 USA. EM lagutc@gmail.com RI Roundtree, Aimee/B-8838-2012; OI Asch, David/0000-0002-7970-286X; Kaufman, Elinore/0000-0001-7550-0024 FU The Robert Wood Johnson Foundation Clinical Scholars Program FX Funding: Supported in part by The Robert Wood Johnson Foundation Clinical Scholars Program. NR 28 TC 88 Z9 89 U1 2 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2008 VL 23 IS 10 BP 1642 EP 1646 DI 10.1007/s11606-008-0726-6 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 347LD UT WOS:000259142200016 PM 18649110 ER PT J AU Hausmann, LRM Jeong, K Bost, JE Ibrahim, SA AF Hausmann, Leslie R. M. Jeong, Kwonho Bost, James E. Ibrahim, Said A. TI Perceived discrimination in health care and use of preventive health services SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE perceived discrimination; preventive health; behavioral risk factor surveillance system; centers for disease control and prevention ID RACISM; EXPERIENCES; POPULATION; COMMUNITY AB OBJECTIVE: To examine the relationship between perceived discrimination and preventive health care utilization. DESIGN AND PARTICIPANTS: Cross-sectional analysis using the 2004 Behavioral Risk Factor Surveillance System "Reactions to Race" module (N = 28,839). MEASUREMENTS: Outcomes were self-reported utilization of seven preventive health services. Predictors included perceived negative and positive racial discrimination ( vs. none) while seeking health care in the past year. Multivariable models adjusted for additional patient characteristics. MAIN RESULTS: In unadjusted models, negative discrimination was significantly associated with less utilization of mammogram, pap test, PSA test, blood stool test, and sigmoidoscopy/colonoscopy (ORs = 0.53-0.73, p <.05), but not flu or pneumococcal vaccines (ORs = 0.76 and 0.84). Positive discrimination was significantly associated with more utilization of all services (ORs = 1.29-1.58, p <.05) except pap test (OR = 0.94). In adjusted models, neither negative nor positive discrimination was predictive of utilization, except for PSA test (positive discrimination OR = 1.33, p <.05). CONCLUSIONS: Perceived racial discrimination in health care does not independently predict preventive health care utilization. C1 [Hausmann, Leslie R. M.; Ibrahim, Said A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15206 USA. [Jeong, Kwonho] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Bost, James E.] Univ Pittsburgh, Ctr Data, Ctr Res Hlth Care, Pittsburgh, PA USA. [Ibrahim, Said A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA. EM leslie.hausmann@gmail.com FU NCRR NIH HHS [UL1 RR024153]; NIAMS NIH HHS [1K24AR055259-01, K24 AR055259] NR 15 TC 30 Z9 30 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2008 VL 23 IS 10 BP 1679 EP 1684 DI 10.1007/s11606-008-0730-x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 347LD UT WOS:000259142200022 PM 18649109 ER PT J AU Dyer, G Lozano-Calderon, S Gannon, C Baratz, M Ring, D AF Dyer, George Lozano-Calderon, Santiago Gannon, Caitlin Baratz, Mark Ring, David TI Predictors of Acute Carpal Tunnel Syndrome Associated With Fracture of the Distal Radius SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Distal radius fracture; acute carpal tunnel syndrome; risk factors ID VOLAR COMPARTMENT SYNDROME; ACUTE MEDIAN NEUROPATHY; FOREARM; DECOMPRESSION; SECONDARY; NERVE; END AB Purpose A better understanding of the risk factors for acute carpal tunnel syndrome (CTS) associated with fracture of the distal radius might influence recommendations for prophylactic carpal tunnel release. Methods Fifty patients who had release of an acute CTS in association with open reduction and internal fixation (ORIF) of a fracture of the distal radius were identified from orthopedic trauma databases at 2 institutions. Each patient was matched with a control patient (ORIF, but no acute CTS) of the same gender, similar age (+/- 4 years), and similar injury mechanism. Results The prevalence of acute CTS among patients with a surgically treated fracture of the distal radius was 5.4%. In univariate analysis, only fracture translation was a significant predictor of acute CTS, but ipsilateral upper extremity trauma and status as a multitrauma patient were nearly significant. The best multivariate model included fracture translation alone and accounted for 60% of the observed increase in risk. A subgroup analysis using receiver operating characteristics (ROC) identified a threshold of approximately 35% fracture translation associated with a significantly increased risk of acute CTS in women less than 48 years of age. No threshold was identified in the other 3 subgroups. Conclusions Fracture translation is the most important risk factor for acute CTS in patients who subsequently had ORIF of a fracture of the distal radius. On the basis of these data, prophylactic carpal tunnel release might be appropriate in women less than 48 years of age with greater than 35% fracture translation, but further investigation is needed to confirm that a true threshold exists. (J Hand Surg 2008;33A:1309-1313. Copyright (C) 2008 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA. Harvard Brigham & Womens Orthopaed Upper Extrem F, Boston, MA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 21 TC 20 Z9 22 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2008 VL 33A IS 8 BP 1309 EP 1313 DI 10.1016/j.jhsa.2008.04.012 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 360HR UT WOS:000260049100007 PM 18929193 ER PT J AU Lettmeier, B Muhlberger, N Schwarzer, R Sroczynski, G Wright, D Zeuzem, S Siebert, U AF Lettmeier, Beate Muehlberger, Nikolai Schwarzer, Ruth Sroczynski, Gaby Wright, Davene Zeuzem, Stefan Siebert, Uwe TI Market uptake of new antiviral drugs for the treatment of hepatitis C SO JOURNAL OF HEPATOLOGY LA English DT Article DE hepatitis C; peginterferon; market uptake; market access ID ALPHA-2B PLUS RIBAVIRIN; QUALITY-OF-LIFE; VIRUS-INFECTION; INITIAL TREATMENT; COST-EFFECTIVENESS; INTERFERON-ALPHA; GENOTYPE DISTRIBUTION; COMBINATION THERAPY; ECONOMIC-EVALUATION; TURKISH PATIENTS AB Background/Aims: Peginterferon plus ribavirin is the state-of-the-art antiviral therapy for prevention of serious complications of hepatitis C. Our aim was to compare market uptake of and access to these drugs across Europe. Methods: We collected launch and sales data for peginterferons for 21 countries in the WHO European region and compared country-specific sales rates. Additionally, we converted sales figures into patient numbers and related those to country-specific hepatitis C prevalence, taking into account genotype distribution, patient characteristics and practice patterns. Results: Peginterferon sales rates differed considerably across countries. The earliest, most rapid and highest adoption rates were in EU founder states, followed by EU members that joined after foundation, and EU non-member states. Most new member states showed a marked increase in sales. By the end of 2005, approximately 308,000 patients had been treated with peginterferons in the 21 countries evaluated. The number of patients ever treated ranged from 16% of prevalent cases in France to less than 1% of cases in Romania, Poland, Greece and Russia. Conclusions: Peginterferon market uptake and access differed considerably across Europe. suggesting unequal access to optimised therapy. Besides budget restrictions, national surveillance and treatment policies should be considered as reasons for market access variation. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Lettmeier, Beate; Muehlberger, Nikolai; Schwarzer, Ruth; Sroczynski, Gaby; Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, UMIT, Dept Publ Hlth Med Decis Making & Hlth Technol As, A-6060 Hall In Tirol, Austria. [Wright, Davene; Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Zeuzem, Stefan] Univ Frankfurt, Dept Internal Med Gastroenterol Hepatol Pneumol &, Frankfurt, Germany. RP Siebert, U (reprint author), Univ Hlth Sci Med Informat & Technol, UMIT, Dept Publ Hlth Med Decis Making & Hlth Technol As, EWZ 1, A-6060 Hall In Tirol, Austria. EM public-health@umit.at FU Hoffman La-Roche Ltd., Basel, Switzerland FX This project was supported in part by an unrestricted educational grant from Hoffman La-Roche Ltd., Basel, Switzerland. The authors had complete and independent control over study design, analysis and interpretation of data. report writing, and publication, regardless of results. We want to thank the members of the PanEuropean Hepatitis C Expert Panel for providing local data and reviewing the results of our study: A. Alberti (University of Padova), M. Buti (Liver Unit, Hospital Universitario Valle Hebron , Barcelona): F.A. Caruntu(Matei Bals National Infectious Disease Institute, Bucharest); C. Gore (The Hepatitis C Trust, London): S. Holmberg, (Division of Viral Hepatitis. CDC, Atlanta); A. Horban (Hospital of InfectiClUs Diseases. Warsaw): P. Mathurill Service d Hepatologie CHRU, Lille) N. Piorkowsky (ELPA, Meckenheim); W. Rosenberg (Institute of Hepatology. University College London): O. Weiland (Division Of Infectious Diseases, Karolinska Institutet, Stockholm): C. Yurdaydin (Gastroenterology Section, University of Ankara Medical School, Ankara). However, the findings and conclusions in this publication are exclusively those of the authors. NR 63 TC 68 Z9 70 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD OCT PY 2008 VL 49 IS 4 BP 528 EP 536 DI 10.1016/j.jhep.2008.04.021 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 358YO UT WOS:000259953600008 PM 18682313 ER PT J AU Morgan, TR Lambrecht, RW Bonkovsky, HL Chung, RT Naishadham, D Sterling, RK Fontana, RJ Lee, WM Ghany, MG Wright, EC O'Brien, TR AF Morgan, Timothy R. Lambrecht, Richard W. Bonkovsky, Herbert L. Chung, Raymond T. Naishadham, Deepa Sterling, Richard K. Fontana, Robert J. Lee, William M. Ghany, Marc G. Wright, Elizabeth C. O'Brien, Thomas R. CA HALT C Trial Grp TI DNA polymorphisms and response to treatment in patients with chronic hepatitis C: Results from the HALT-C trial SO JOURNAL OF HEPATOLOGY LA English DT Article DE hepatitis C; chronic/genetics; polymorphism; genetic; interferon-alfa/therapeutic use; gene frequency ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-10 GENE PROMOTER; VIRUS-INFECTION; FACTOR-ALPHA; COMBINATION THERAPY; TNF-ALPHA; PEGINTERFERON ALPHA-2A; INTERFERON-ALPHA; PLUS RIBAVIRIN; LIVER-DISEASE AB Background/Aims: Certain host genetic polymorphisms reportedly affect the likelihood of a sustained virological response (SVR) to interferon treatment in subjects infected with hepatitis C virus (HCV). As part of the HALT-C trial we evaluated genetic associations among patients infected with HCV genotype 1 who had failed previous interferon treatment. Methods: SVR was determined 24 weeks after completing treatment with pegylated interferon alfa-2a and ribavirin. Eight single nucleotide polymorphisms (SNPs) were selected on the basis of previously reported associations with treatment response. Genotypes were assessed by polymerase chain reaction-based assays. The percentage of patients who achieved SVR was determined for each genotype and for an IL10 promoter diplotype. Results: Among 637 non-Hispanic Caucasian patients there were no significant associations between genotype for any individual SNP (IL10-1082, IL10-592, TNF-308, TNF-238, TGFB1 codon 25, CCL2-2518, EPHX1 codon 113 and AGT-6) and SVR, but SVR was more common among the patients who were homozygous for the ACC IL10 promoter diplotype (adjusted odds ratio, 3.24; 95% confidence interval, 1.33-7.78; p = 0.001). Conclusions: Among non-Hispanic Caucasian patients treated with peginterferon and ribavirin after failing previous treatment with interferon, homozygosity for the ACC IL10 promoter diplotype was associated with SVR. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA 92717 USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Lambrecht, Richard W.; Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA. [Sterling, Richard K.] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA. [Fontana, Robert J.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Wright, Elizabeth C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [O'Brien, Thomas R.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Morgan, TR (reprint author), Univ Calif Irvine, Div Gastroenterol, Irvine, CA 92717 USA. EM timothy.morgan@va.gov FU Intramural NIH HHS [Z99 CA999999, Z99 DK999999]; NCRR NIH HHS [M01 RR-00043, M01 RR000827, M01 RR001066, M01 RR-00042, M01 RR-00827, M01 RR-00633, M01 RR-06192, M01 RR000065, M01 RR000043, M01 RR-00051, M01 RR-01066, M01 RR006192, M01 RR-00065, M01 RR000051, M01 RR000042, M01 RR000633]; NIDDK NIH HHS [N01-DK-9-2326, N01-DK-9-2324, N01 DK092327, N01-DK-9-2323, N01DK92327, N01 DK092318, N01-DK-9-2322, N01-DK-9-2327, N01 DK092326, N01 DK092320, N01-DK-9-2328, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2318, N01-DK-9-2319, N01 DK092319, N01 DK092323, N01 DK092328, N01 DK092325, N01 DK092324, N01 DK092321, N01-DK-9-2325] NR 40 TC 34 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD OCT PY 2008 VL 49 IS 4 BP 548 EP 556 DI 10.1016/j.jhep.2008.05.011 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 358YO UT WOS:000259953600010 PM 18619701 ER PT J AU Musher, DM Rueda, AM Nahm, MH Graviss, EA Rodriguez-Barradas, MC AF Musher, Daniel M. Rueda, Adriana M. Nahm, Moon H. Graviss, Edward A. Rodriguez-Barradas, Maria C. TI Initial and subsequent response to pneumococcal polysaccharide and protein-conjugate vaccines administered sequentially to adults who have recovered from pneumococcal pneumonia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 12-15, 2006 CL Toronto, CANADA SP Infect Dis Soc Amer ID HIV-INFECTED ADULTS; STREPTOCOCCUS-PNEUMONIAE; ANTIBODY-RESPONSES; RANDOMIZED-TRIAL; OLDER-ADULTS; T-CELLS; B-CELLS; IMMUNOGENICITY; IMMUNIZATION; EFFICACY AB Background. Controversy persists over the benefits of pneumococcal polysaccharide vaccine (PPV) for adults at high risk for pneumococcal disease. We studied PPV, protein-conjugate pneumococcal vaccine (PCV), and immunologic "priming" with PCV followed by "boosting" with PPV in adults who had recovered from pneumococcal pneumonia. Methods. Subjects received PPV followed by PCV 6 months later, or vice versa. The levels of IgG to capsular polysaccharide and opsonophagocytic killing activity (OPK) were studied at baseline and at 4-8 weeks and 6 months after each vaccination. Results. PPV and PCV stimulated similar IgG levels and OPK at 4-8 weeks after vaccination. Six months after receipt of PPV, the antibody levels declined to baseline but remained modestly elevated after receipt of PCV. PCV administered 6 months after PPV stimulated modest increases in IgG level that failed to reach the peaks observed after receipt of PPV. In contrast, PPV administered 6 months after PCV caused dramatic increases in the levels of IgG and OPK for all polysaccharides at 4-8 weeks, consistent with a booster effect. Six months after receipt of the second vaccination, however, levels of IgG and OPK fell precipitously in all patients, approaching baseline levels. Conclusions. In these high-risk subjects who have recovered after treatment for pneumonia, the effect of PPV is short-lived; PCV stimulates a more prolonged response. The use of PPV as a booster following PCV causes early increases in antibody levels, but the level of IgG declines rapidly thereafter, consistent with induction of suppressor cells or tolerance. Protein vaccines may be needed for high-risk adults. C1 [Musher, Daniel M.; Rueda, Adriana M.; Rodriguez-Barradas, Maria C.] Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Houston, TX 77030 USA. [Musher, Daniel M.; Rueda, Adriana M.; Graviss, Edward A.; Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Graviss, Edward A.] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Nahm, Moon H.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Musher, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Room 4B-370,2002 Holcombe Blvd, Houston, TX 77030 USA. EM daniel.musher@med.va.gov OI Nahm, Moon/0000-0002-6922-1042 FU NIAID NIH HHS [AI-69695, R01 AI069509, R01 AI069509-02] NR 45 TC 52 Z9 52 U1 0 U2 0 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 OCT 1 PY 2008 VL 198 IS 7 BP 1019 EP 1027 DI 10.1086/591629 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 345EO UT WOS:000258979100011 PM 18710324 ER PT J AU Jayasekera, CR Harris, JB Bhuiyan, S Chowdhury, F Khan, AI Faruque, ASG LaRocque, RC Ryan, ET Ahmed, R Qadri, F Calderwood, SB AF Jayasekera, Channa R. Harris, Jason B. Bhuiyan, Saruar Chowdhury, Fahima Khan, Ashraful I. Faruque, Abu S. G. LaRocque, Regina C. Ryan, Edward T. Ahmed, Rafi Qadri, Firdausi Calderwood, Stephen B. TI Cholera toxin-specific memory B cell responses are induced in patients with dehydrating diarrhea caused by Vibrio cholerae O1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 42nd United States-Japan Conference on Cholera and Other Bacterial Enteric Infections CY DEC, 2007 CL Austin, TX SP US Japan Cooperat Med Sci Program ID RURAL EAST PAKISTAN; VACCINE FIELD-TRIAL; IMMUNE-RESPONSES; ENTERIC INFECTIONS; MUCOSAL; ANTIGEN; IMMUNIZATION; BANGLADESH; ALPHA-4-BETA-7; EXPRESSION AB Background. Infection with Vibrio cholerae induces durable immunity against subsequent disease, a process hypothesized to reflect anamnestic immune responses at the intestinal mucosa. The presence of antigen-specific memory B cells may therefore be a more direct measure of protection than serum antibody responses. Methods. We measured immunoglobulin (Ig) G memory B cells specific to cholera toxin B subunit (CTB) in 14 patients up to 90 days after V. cholerae O1 infection, by polyclonal stimulation of peripheral blood mononuclear cells followed by standard enzyme-linked immunospot assay. Results. All patients generated CTB-specific IgG memory B cell responses by day 30 (mean, 0.10% of total circulating IgG memory B cells; range, 0.037% - 0.28%), which persisted to day 90 (mean, 0.07%; range, 0.003% - 0.27%). In contrast, circulating CTB-specific IgG antibody-secreting cells and serum vibriocidal and anti-CTB antibody responses peaked on day 7 and declined to undetectable or significantly lower levels by day 90. Conclusions. CTB-specific IgG memory B cell responses are detectable in the circulation at least 3 months after V. cholerae O1 infection and remain measurable even after serum antibody titers have declined to undetectable or considerably lower levels. This suggests that antigen-specific memory B cells may be an important long-term marker of the immune response to cholera. C1 [Harris, Jason B.; LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Jayasekera, Channa R.; Bhuiyan, Saruar; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Lab Div, Dhaka 1000, Bangladesh. [Chowdhury, Fahima; Khan, Ashraful I.; Faruque, Abu S. G.] Int Ctr Diarrhoeal Dis Res, Div Clin Sci, Dhaka 1000, Bangladesh. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM jbharris@partners.org FU FIC NIH HHS [D43 TW005572, K01 TW007144, K01 TW007144-05, K01 TW007409, K01 TW07144, K01 TW07409, D43 TW005572-05S2, K01 TW007409-04]; NIAID NIH HHS [R01 AI040725, R01 AI040725-10, R01 AI40725, T32 AI007061, R03 AI063079-03, R03 AI063079, U01 AI058935, U01 AI058935-09] NR 25 TC 25 Z9 27 U1 1 U2 3 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 OCT 1 PY 2008 VL 198 IS 7 BP 1055 EP 1061 DI 10.1086/591500 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 345EO UT WOS:000258979100015 PM 18729782 ER PT J AU Garcia, S McFalls, EO Goldman, S Larsen, GC Littooy, F Moritz, TE Reda, DJ Ward, HB Shunk, K Hattler, B AF Garcia, Santiago McFalls, Edward O. Goldman, Steven Larsen, Greg C. Littooy, Fred Moritz, Thomas E. Reda, Domenic J. Ward, Herbert B. Shunk, Kendrick Hattler, Brack TI Diagnostic coronary angiography in patients with peripheral arterial disease: A sub-study of the Coronary Artery Revascularization Prophylaxis trial SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID MAJOR VASCULAR-SURGERY; PERIOPERATIVE CARDIOVASCULAR EVALUATION; CARDIAC-CATHETERIZATION; NONCARDIAC SURGERY; COMPLICATIONS; RISK; ARTERIOGRAPHY; INTERVENTIONS; GUIDELINES; SOCIETY AB Background: Although patients in need of elective vascular surgery are often considered candidates for diagnostic coronary angiography, the safety of this invasive study has not been systematically studied in a large cohort of patients scheduled for an elective vascular operation. The goal of this sub-study of the Coronary Artery Revascularization Prophylaxis (CARP) trial was to assess the safety of coronary angiography in patients with peripheral vascular disease. Methods: The CARP trial tested the long-term benefit of coronary artery revascularization prior to elective vascular operations. Among those patients who underwent diagnostic coronary angiography during screening for the trial, the associated complications were determined at 24 hours following the diagnostic procedure. Results: Over 5,000 patients were screened during a 4-year recruitment period at 18 major VA medical centers and the present cohort consists of 1,298 patients who underwent preoperative coronary angiography. Surgical indications for vascular surgery included an expanding aortic aneurysm (AAA) (n = 446; 34.4%) or arterial occlusive disease with either claudication (n = 457; 35.2%) or rest pain (n = 395; 30.4%). A total of 39 patients had a confirmed complication with a major complication identified in 17 patients (1.3%). Complication rates were higher in patients with arterial occlusive symptoms compared with expanding aneurysms (1.8% vs. 0.5%; P = 0.07) and were not dissimilar with femoral (2.8%) versus nonfemoral (4.7%) access sites (P = 0.42). Conclusions: Coronary angiography is safe in patients with peripheral arterial disease undergoing preoperative coronary angiography. The complication rate is higher in patients with symptoms of arterial occlusive disease. C1 [Garcia, Santiago; McFalls, Edward O.; Ward, Herbert B.] Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA. [Garcia, Santiago; McFalls, Edward O.; Ward, Herbert B.] Univ Minnesota, Minneapolis, MN USA. [Goldman, Steven] Univ Arizona, Sarver Heart Ctr, Tucson, AZ USA. [Goldman, Steven] So Arizona VA Hlth Care Syst, Tucson, AZ USA. [Larsen, Greg C.] Oregon Hlth & Sci Univ, Portland, OR USA. [Larsen, Greg C.] Oregon VA Med Ctr, Portland, OR USA. [Littooy, Fred; Moritz, Thomas E.; Reda, Domenic J.] Hines VA Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL USA. [Shunk, Kendrick] San Francisco VA Med Ctr, San Francisco, CA USA. [Shunk, Kendrick] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hattler, Brack] Denver VA Med Ctr, Denver, CO USA. RP McFalls, EO (reprint author), VA Med Ctr, Div Cardiol 111C, 1 Vet Dr, Minneapolis, MN 55417 USA. EM mcfal001@umn.edu FU Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development FX The CARP trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development. NR 18 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0896-4327 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD OCT PY 2008 VL 21 IS 5 BP 369 EP 374 DI 10.1111/j.1540-8183.2008.00391.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 357IK UT WOS:000259839300001 PM 18761563 ER PT J AU Kiernan, T Yan, BP Rosenfield, K Gupta, V AF Kiernan, Tom Yan, Bryan P. Rosenfield, Kenneth Gupta, Vishal TI Coil embolization of an iatrogenic coronary artery to cardiac vein fistula after rotational atherectomy SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID ANGIOPLASTY; EXPERIENCE AB Iatrogenic coronary arteriovenous fistulae (AVF) are a rare albeit serious complication of percutaneous coronary artery intervention. We report, to our knowledge, the first case of an AVF originating from the left anterior descending artery (LAD), draining into the great cardiac vein as a result of rotational atherectomy in a complex calcified lesion, complicated by congestive cardiac failure and subsequent percutaneous coil embolization of the AVF. C1 [Kiernan, Tom; Yan, Bryan P.; Rosenfield, Kenneth; Gupta, Vishal] Massachusetts Gen Hosp, Div Intervent Cardiol, Boston, MA 02114 USA. RP Kiernan, T (reprint author), Massachusetts Gen Hosp, Div Intervent Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM tom_kiernan@hotmail.com RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015 NR 13 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0896-4327 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD OCT PY 2008 VL 21 IS 5 BP 410 EP 413 DI 10.1111/j.1540-8183.2008.00360.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 357IK UT WOS:000259839300008 PM 18513344 ER PT J AU Bhatt, DL AF Bhatt, Deepak L. TI Is it Time to Switch to Radial Access? SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Editorial Material C1 [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.] TIMI Study Grp, Boston, MA USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM dlbhattmd@alum.mit.edu NR 14 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD OCT PY 2008 VL 20 IS 10 BP A6 EP + PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V14MU UT WOS:000207739300002 PM 18924288 ER PT J AU Bird, KG Meyer, L Dellavalle, RP AF Bird, K. G. Meyer, L. Dellavalle, R. P. TI Reduced incidence of melanoma in a VA population using statins: a case-control study SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Congress of the International-Dermato-Epidemiology-Association CY SEP 07-11, 2008 CL Nottingham, ENGLAND SP Int Dermato Epidemiol Assoc C1 [Bird, K. G.] Univ Colorado, Denver AMC, Denver, CO 80262 USA. [Meyer, L.] VA Salt Lake City HCS, Salt Lake City, UT 84148 USA. [Dellavalle, R. P.] Denver VA Med Ctr, Denver, CO 80220 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2008 VL 128 IS 10 MA 21 BP 2553 EP 2553 PG 1 WC Dermatology SC Dermatology GA 348RW UT WOS:000259228600051 ER PT J AU Dellavalle, RP AF Dellavalle, R. P. TI Benchmarking US department of veterans affairs dermatologic mission fulfillment SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Congress of the International-Dermato-Epidemiology-Association CY SEP 07-11, 2008 CL Nottingham, ENGLAND SP Int Dermato Epidemiol Assoc C1 [Dellavalle, R. P.] Univ Colorado, Denver AMC, Denver, CO 80262 USA. [Dellavalle, R. P.] Denver VA Med Ctr, Denver, CO 80220 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2008 VL 128 IS 10 MA 23 BP 2553 EP 2553 PG 1 WC Dermatology SC Dermatology GA 348RW UT WOS:000259228600052 ER PT J AU Njoku, C Self, SE Ruiz, P Hofbauer, AF Gilkeson, GS Oates, JC AF Njoku, Chinedu Self, Sally E. Ruiz, Philip Hofbauer, Ann F. Gilkeson, Gary S. Oates, Jim C. TI Inducible nitric oxide synthase inhibitor SD-3651 reduces proteinuria in MRL/lpr mice deficient in the NOS2 gene SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE lupus nephritis; nitric oxide; animal models; nitric oxide synthase; enzyme inhibitors ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MRL-LPR/LPR MICE; GLOMERULAR PODOCYTOPATHY; AUTOIMMUNE-DISEASE; RENAL-DISEASE; ARGININE; ANTIOXIDANT; GLOMERULONEPHRITIS; NEPHROPATHY; MODULATION AB Several studies have demonstrated the effectiveness of arginine analog nitric oxide synthase (NOS) inhibitor therapy in preventing and treating murine lupus nephritis. However, MRL/MpJ-FAS(lpr) (MRL/lpr) mice lacking a functional NOS2 (inducible NOS [iNOS]) gene (NOS2(-/-)) develop proliferative glomerulonephritis in a fashion similar to their wild-type (wt) littermates. This finding suggests that the effect of arginine analog NOS inhibitors is through a non-iNOS-mediated mechanism. This study was designed to address this hypothesis. NOS2(-/-) mice were given either vehicle or a NOS inhibitor (SD-3651) to determine if pharmacological NOS inhibition prevented glomerulonephritis, using wt rnice as positive controls. Urine was collected fortnightly to measure albumin. At the time of full disease expression in wt rnice, all mice were killed, and renal tissue was examined for light, immunofluorescence, and electron microscopic evidence of disease. Scrum was analyzed for anti-double-stranded DNA antibody production. NOS2(-/-) mice had higher serum anti-double-stranded DNA antibody antibody levels than those of wt mice. SD-3651 therapy reduced proteinuria, glomerular immunoglobulin G deposition, and electron microscopic evidence of podocytopathy and endothelial cell swelling without affecting proliferative lesions by light microscopy. These studies confirm that genetic iNOS deficiency alone is insufficient to prevent proliferative glomerulonephritis and suggest that iNOS activity may inhibit autoantibody production. These results also suggest that SD-3651 therapy acts via a non-iNOS-mediated mechanism to prevent endothelial cell and podocyte pathology. Studies that elucidate this mechanism could provide a useful drug target for the treatment of nephritis. C1 [Njoku, Chinedu; Gilkeson, Gary S.; Oates, Jim C.] Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. [Self, Sally E.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Ruiz, Philip] Univ Miami, Leonard M Miller Sch Med, Dept Surg, Miami, FL USA. [Ruiz, Philip] Univ Miami, Leonard M Miller Sch Med, Dept Pathol, Miami, FL USA. [Hofbauer, Ann F.; Gilkeson, Gary S.; Oates, Jim C.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. RP Oates, JC (reprint author), 96 Jonathan Lucas St,Suite 912,MSC 637, Charleston, SC 29425 USA. EM oatesjc@musc.edu FU National Institutes of Health, Bethesda, MD [K08AR002193, R01AR045476]; Career Development, Research Enhancement Award Program; Medical Research Service; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC FX The work of Drs Oates and Gilkeson was supported by grants K08AR002193 and R01AR045476 from the National Institutes of Health, Bethesda, MD, and Career Development, Research Enhancement Award Program, and Merit Review grants from the Medical Research Service, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC. NR 29 TC 11 Z9 11 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD OCT PY 2008 VL 56 IS 7 BP 911 EP 919 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 358YV UT WOS:000259954300008 PM 18797415 ER PT J AU Sundararaj, KP Samuvel, DJ Li, YC Nareika, A Slate, EH Sanders, JJ Lopes-Virella, MF Huang, Y AF Sundararaj, Kamala P. Samuvel, Devadoss J. Li, Yanchun Nareika, Alena Slate, Elizabeth H. Sanders, John J. Lopes-Virella, Maria F. Huang, Yan TI Simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by inhibiting protein isoprenylation-mediated ERK activation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT Pennington Scientific Symposium on Neuro-Immune Signaling and Inflammation CY DEC 02-05, 2007 CL Baton Rouge, LA DE matrix metalloproteinases; statin; lipopolysaccharide; mitogen-activated protein kinase; gene expression ID KAPPA-B ACTIVATION; MATRIX METALLOPROTEINASES; TRANSCRIPTION FACTORS; LIPOPOLYSACCHARIDE; STATINS; COLLAGENASE; INDUCTION; MONOCYTES; PERIODONTITIS; MACROPHAGES AB Matrix metalloproteinase (MMP) plays a crucial role in periodontal disease and is up-regulated by oral Gram-negative, pathogen-derived LPS. In this study, we reported that simvastatin, a 3-hydroxyl-3-methylglutaryl-CoA reductase inhibitor, effectively inhibited LPS-stimulated MMP-1 as well as MMP-8 and MMP-9 expression by U937 mononuclear cells. Our studies showed that the geranylgeranyl transferase inhibitor inhibited LPS-stimulated MMP-1 expression, and addition of isoprenoid intermediate geranylgeranyl pyrophosphate (GGPP) reduced the inhibitory effect of simvastatin on LPS-stimulated MMP-1 expression. We also demonstrated that simvastatin inhibited the activation of Ras and Rac, and the inhibition was abolished by addition of GGPP. The above results indicate that protein isoprenylation is involved in the regulation of MMP-1 expression by LPS and simvastatin. Moreover, we showed that simvastatin inhibited LPS-stimulated nuclear AP-1, but not NF-kappa B activity, and the inhibition was reversed by addition of GGPP. Simvastatin also inhibited LPS-stimulated ERK but not p38 MAPK and JNK. Finally, we showed that the inhibition of LPS-stimulated ERK activation by simvastatin was reversed by GGPP. Taken together, this study showed that simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by targeting protein isoprenylation-mediated ERK activation. C1 [Huang, Yan] Med Univ S Carolina, Dept Med, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Sundararaj, Kamala P.; Samuvel, Devadoss J.; Nareika, Alena; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29403 USA. [Slate, Elizabeth H.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29403 USA. [Sanders, John J.] Med Univ S Carolina, Dept Stomatol, Div Periodont, Charleston, SC 29403 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Dept Med, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU NIDCR NIH HHS [R01 DE016353, DE16353] NR 28 TC 26 Z9 27 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD OCT 1 PY 2008 VL 84 IS 4 BP 1120 EP 1129 DI 10.1189/jlb.0108064 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 354KW UT WOS:000259639500029 PM 18625914 ER PT J AU Kerwin, WS Liu, F Yarnykh, V Underhill, H Oikawa, M Yu, W Hatsukami, TS Yuan, C AF Kerwin, William S. Liu, Fei Yarnykh, Vasily Underhill, Hunter Oikawa, Minako Yu, Wei Hatsukami, Thomas S. Yuan, Chun TI Signal features of the atherosclerotic plaque at 3.0 Tesla versus 1.5 Tesla: Impact on automatic classification SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE carotid artery; MRI; atherosclerosis; segmentation; field strength ID MAGNETIC-FIELD STRENGTHS; IN-VIVO ACCURACY; BLACK-BLOOD MRI; CAROTID PLAQUE; HIGH-RESOLUTION; INTRAPLAQUE HEMORRHAGE; INVERSION-RECOVERY; CEREBRAL-ISCHEMIA; FIBROUS-CAP; ASSOCIATION AB Purpose: To investigate the impact of different field strengths on determining plaque composition with an automatic classifier. Materials and Methods: We applied a previously developed automatic classifier-the morphology enhanced probabilistic plaque segmentation (MEPPS) algorithm-to images from 20 subjects scanned at both 1.5 Tesla (T) and 3T. Average areas per slice of lipid-rich core, intraplaque hemorrhage, calcification, and fibrous tissue were recorded for each subject and field strenght. Results: All measurements showed close agreement at the two field strengths, with correlation coefficients of 0.91, 0.93, 0.95, and 0.93, respectively. None of these measurements showed a statistically significant difference between field strengths in the average area per slice by a paired t-test, although calcification tended to be measured larger at 3T (P = 0.09). Conclusion: Automated classification results using an identical algorithm at 1.5T and 3T produced highly similar results, suggesting that with this acquisition protocol, 3T signal characteristics of the atherosclerotic plaque are sufficiently similar to 1.5T characteristics for MEPPS to provide equivalent performance. C1 [Kerwin, William S.; Liu, Fei; Yarnykh, Vasily; Underhill, Hunter; Oikawa, Minako; Yu, Wei; Yuan, Chun] Univ Washington, Dept Radiol, Seattle, WA 98109 USA. [Hatsukami, Thomas S.] Univ Washington, Dept Surg, Seattle, WA 98109 USA. [Hatsukami, Thomas S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Kerwin, WS (reprint author), Univ Washington, Dept Radiol, 815 Mercer St,Box 358050, Seattle, WA 98109 USA. EM bkerwin@u.washington.edu RI Yarnykh, Vasily/G-8757-2016; Yarnykh, Vasiliy/N-7635-2014 OI Yarnykh, Vasily/0000-0002-1583-8979; FU NIH [R01-HL056874, R44-HL070576, P01-HL072262, R01-HL073401]; Pfizer FX Contract grant sponsor: NIH; Contract grant number: R01-HL056874; Contract grant number: R44-HL070576; Contract grant number: P01-HL072262; Contract grant number: R01-HL073401; Contract grant sponsor: Pfizer. NR 28 TC 24 Z9 24 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD OCT PY 2008 VL 28 IS 4 BP 987 EP 995 DI 10.1002/jmri.21529 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 356PY UT WOS:000259791300021 PM 18821634 ER PT J AU Zelinski, AC Angelone, LM Goyal, VK Bonmassar, G Adalsteinsson, E Wald, LL AF Zelinski, Adam C. Angelone, Leonardo M. Goyal, Vivek K. Bonmassar, Giorgio Adalsteinsson, Elfar Wald, Lawrence L. TI Specific absorption rate studies of the parallel transmission of inner-volume excitations at 7T SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE RF safety; parallel transmission; specific absorption rate (SAR); RF pulse design; FDTD simulation; multichannel transmit array ID RF TRANSMISSION; FUNCTIONAL MRI; BIRDCAGE COIL; ARRAY; POWER; HEAD; RESONANCE; BOUNDARY; STRENGTH; CHANNELS AB Purpose: To investigate the behavior of whole-head and local specific absorption rate (SAR) as a function of trajectory acceleration factor and target excitation pattern due to the parallel transmission (pTX) of spatially tailored excitations at 7T. Materials and Methods: Finite-difference time domain (FDTD) simulations in a multitissue head model were used to obtain B-1(+) and electric field maps of an eight-channel transmit head array. Local and average SAR produced by 2D-spiral-trajectory excitations were examined as a function of trajectory acceleration factor, R, and a variety of target excitation parameters when pTX pulses are designed for constant root-mean-square excitation pattern error. Results: Mean and local SAR grow quadratically with flip angle and more than quadratically with R, but the ratio of local to mean SAR is not monotonic with R. SAR varies greatly with target position, exhibiting different behaviors as a function of target shape and size for small and large R. For example, exciting large regions produces less SAR than exciting small ones for R >= 4, but the opposite trend occurs when R < 4 . Furthermore, smoother and symmetric patterns produce lower SAR. Conclusion: Mean and local SAR vary by orders of magnitude depending on acceleration factor and excitation pattern, often exhibiting complex, nonintuitive behavior. To ensure safety compliance, it seems that model-based validation of individual target patterns and corresponding pTX pulses is necessary. C1 [Zelinski, Adam C.; Goyal, Vivek K.; Adalsteinsson, Elfar] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Angelone, Leonardo M.; Bonmassar, Giorgio; Wald, Lawrence L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Adalsteinsson, Elfar; Wald, Lawrence L.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Zelinski, AC (reprint author), 77 Massachusetts Ave,Rm 36-680, Cambridge, MA 02139 USA. EM zelinski@MIT.edu RI Adalsteinsson, Elfar/F-2477-2010; Wald, Lawrence/D-4151-2009; OI Angelone, Leonardo/0000-0002-1105-021X FU National Institutes of Health (NIH) [NCRR P41RR14075, NIBIB 1R01EB006847, 1R01EB007942, 1R01EB000790]; MIND Institute; Siemens Medical Solutions; US Department of Defense; NDSEG [F49620-02-C-0041]; R. J. Shillman Career Development Award FX Contract grant sponsor: National Institutes of Health (NIH); Contract grant numbers: NCRR P41RR14075, NIBIB 1R01EB006847, 1R01EB007942, 1R01EB000790; Contract grant sponsor: MIND Institute; Contract grant sponsor: Siemens Medical Solutions; Contract grant sponsor: US Department of Defense; Contract grant number: NDSEG Fellowship F49620-02-C-0041; Contract grant sponsor: R. J. Shillman Career Development Award. NR 47 TC 33 Z9 33 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD OCT PY 2008 VL 28 IS 4 BP 1005 EP 1018 DI 10.1002/jmri.21548 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 356PY UT WOS:000259791300023 PM 18821601 ER PT J AU Chen, LJ Na, R Gu, MJ Richardson, A Ran, Q AF Chen, Liuji Na, Ren Gu, Mingjun Richardson, Arlan Ran, Qitao TI Lipid peroxidation up-regulates BACE1 expression in vivo: a possible early event of amyloidogenesis in Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE beta-amyloid; beta-site amyloid precursor protein cleavage enzyme 1; Alzheimer's disease; amyloid precursor protein transgenic mice; glutathione peroxidase 4; lipid peroxidation ID MILD COGNITIVE IMPAIRMENT; BETA-SECRETASE ACTIVITY; AMYLOID PRECURSOR PROTEIN; OXIDATIVE STRESS; TRANSGENIC MICE; A-BETA; BRAIN; MOUSE; GENERATION; PRODUCT AB Increased lipid peroxidation is shown to be an early event of Alzheimer's disease (AD). However, it is not clear whether and how increased lipid peroxidation might lead to amyloidogenesis, a hallmark of AD. Glutathione peroxidase 4 (Gpx4) is an essential antioxidant defense enzyme that protects an organism against lipid peroxidation. Gpx4+/- mice show increased lipid peroxidation in brain, as evidenced by their elevated levels of 4-hydroxy-2-nonenal. To understand the role of lipid peroxidation in amyloidogenesis, we studied secretase activities in Gpx4+/- mice as a function of age. Both young (6 months) and middle-aged (17-20 months) Gpx4+/- mice had higher levels of beta-secretase activity than their age-matched wildtype controls, and the increased beta-secretase activity in Gpx4+/- mice was a result of up-regulation of beta-site amyloid precursor protein cleavage enzyme 1 (BACE1) expression at the protein level. The high level of BACE1 protein led to increased endogenous beta-amyloid (A beta)(1-40) in middle-aged Gpx4+/- mice. We further studied amyloidogenesis in APPGpx4+/- mice. Our data indicate that APPGpx4+/- mice had significantly increased amyloid plaque burdens and increased A beta(1-40) and A beta(1-42) levels compared with APPGpx4+/+ mice. Therefore, our results indicate that increased lipid peroxidation leads to increased amyloidogenesis through up-regulation of BACE1 expression in vivo, a mechanism that may be important in pathogenesis of AD at early stages. C1 [Chen, Liuji; Na, Ren; Gu, Mingjun; Richardson, Arlan; Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Chen, Liuji; Richardson, Arlan; Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Richardson, Arlan; Ran, Qitao] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Ran, Q (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM ran@uthscsa.edu FU Department of Veteran Affairs; NIH/NIA [K01AG022014] FX The study was supported by a Merit Award (QR) from the Department of Veteran Affairs and a K01AG022014 Award (QR) from NIH/NIA. NR 48 TC 45 Z9 47 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2008 VL 107 IS 1 BP 197 EP 207 DI 10.1111/j.1471-4159.2008.05603.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 349HA UT WOS:000259270700017 PM 18680556 ER PT J AU Zhang, F Chen, J AF Zhang, Feng Chen, Jun TI Leptin protects hippocampal CA1 neurons against ischemic injury SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Akt; extracellular signal-related kinase 1/2; global ischemia; leptin antagonist; neuroprotection ID TRANSIENT FOREBRAIN ISCHEMIA; FOCAL CEREBRAL-ISCHEMIA; SIGNALING MECHANISMS; LONG FORM; ACTIVATION; APOPTOSIS; RECEPTOR; KINASE; DEATH; RAT AB Leptin is an adipose hormone with well characterized roles in regulating food intake and energy balance. A novel neuroprotective role for leptin has recently been discovered; however, the underlying mechanisms are not clearly defined. The purpose of this study was to determine whether leptin protects against delayed neuronal cell death in hippocampal CA1 following transient global cerebral ischemia in rats and to study the signaling mechanism responsible for the neuroprotective effects of leptin. Leptin receptor antagonist, protein kinase inhibitors and western blots were used to assess the molecular signaling events that were altered by leptin after ischemia. The results revealed that intracerebral ventricle infusion of leptin markedly increased the numbers of survival CA1 neurons in a dose-dependent manner. Infusion of a specific leptin antagonist 10 min prior to transient global ischemia abolished the pro-survival effects of leptin, indicating the essential role of leptin receptors in mediating this neuroprotection. Both the Akt and extracellular signal-related kinase 1/2 (ERK1/2) signaling pathways appear to play a critical role in leptin neuroprotection, as leptin infusion increased the phosphorylation of Akt and ERK1/2 in CA1. Furthermore, pharmacological inhibition of either pathway compromised the neuroprotective effects of leptin. Taken together, the results suggest that leptin protects against delayed ischemic neuronal death in the hippocampal CA1 by maintaining the pro-survival states of Akt and ERK1/2 MAPK signaling pathways. C1 [Zhang, Feng; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Zhang, Feng; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Zhang, Feng; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Chen, Jun] Fudan Univ, Sch Med, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomedical Sci Tower, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS43802, NS45048, NS36736, NS 56118] FX This project was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke grants NS43802, NS45048, NS36736, NS 56118 and a VA Merit Review grant. We thank Carol Culver and Aalap C. Shan for editorial assistance and Pat Strickler for secretarial support. NR 40 TC 42 Z9 47 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2008 VL 107 IS 2 BP 578 EP 587 DI 10.1111/j.1471-4159.2008.05645.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 358XD UT WOS:000259949900024 PM 18752642 ER PT J AU Erbay, SH O'Callaghan, M Shah, P Kini, J Midle, JB Polak, JF AF Erbay, Sami H. O'Callaghan, Mark. Shah, Paraq Kini, Jonathan Midle, Jennifer Bassett Polak, Joseph F. TI Prospective evaluation of the role of atherosclerosis on cerebral atrophy: Pilot study SO JOURNAL OF NEUROIMAGING LA English DT Article DE cerebral atrophy; atherosclerosis; arterial calcium ID BEAM COMPUTED-TOMOGRAPHY; MATTER LOW ATTENUATION; BRAIN ATROPHY; CARDIOVASCULAR HEALTH; ALZHEIMERS-DISEASE; RISK-FACTORS; FOLLOW-UP; DEMENTIA; LESIONS; CT AB PURPOSE Our purpose was to study the association between atherosclerosis measured by arterial calcium on computed tomography (CT) and cerebral atrophy demonstrated by brain magnetic resonance imaging (MRI). MATERIALS AND METHODS IRB approved this prospective study. Twenty-one consecutive patients with acute stroke-like symptoms who are scheduled to have brain MRI were recruited on a voluntary basis. electrocardiogram (ECG)-gated helical CT scans were used to determine the arterial calcium as a reliable index of underlying atherosclerosis. Extracranial arterial calcium content was measured quantitatively by special software available in our CT scanner. Intracranial calcium was graded qualitatively. Brain MRI was independently evaluated to identify cortical, central atrophy, and ischemic changes. Relationship between CT demonstrated atherosclerosis and cerebral ischemic changes, brain atrophy patterns were evaluated both without and with adjustment for age and hypertension. RESULTS Out of 21 patients 20 were included in final study group. There was no correlation between atherosclerotic calcium measures and cortical atrophy, ischemic findings. Both intracranial and extracranial atherosclerosis had partial correlation with central atrophy (R = 0.43 and 0.52, respectively). After adjustment for age, only intracranial atherosclerosis maintained a partial correlation with central atrophy (R = 0.41). However, this correlation did not reach a statistically significant level (P = .10). CONCLUSIONS Intracranial atherosclerosis demonstrated a possible correlation with central atrophy. C1 [Erbay, Sami H.; Shah, Paraq; Polak, Joseph F.] Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA 02111 USA. [Midle, Jennifer Bassett] Tufts Univ New England Med Ctr, Dept Biostat, Boston, MA 02111 USA. [O'Callaghan, Mark.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Kini, Jonathan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Erbay, SH (reprint author), Tufts Univ New England Med Ctr, Dept Radiol, NEMC 299,750 Washington St, Boston, MA 02111 USA. EM serbay@msn.com FU New England Medical Center [1042] FX This study is supported by grant No. 1042 from New England Medical Center. NR 28 TC 3 Z9 4 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD OCT PY 2008 VL 18 IS 4 BP 375 EP 380 DI 10.1111/j.1552-6569.2007.00149.x PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 357HG UT WOS:000259836300006 PM 19012736 ER PT J AU Rossetti, AO Logroscino, G Milligan, TA Michaelides, C Ruffieux, C Bromfield, EB AF Rossetti, Andrea O. Logroscino, Giancarlo Milligan, Tracey A. Michaelides, Costas Ruffieux, Christiane Bromfield, Edward B. TI Status Epilepticus Severity Score (STESS) SO JOURNAL OF NEUROLOGY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 30-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc DE status epilepticus; prognosis; treatment; coma induction; outcome ID NONCONVULSIVE STATUS EPILEPTICUS; SEIZURES DAMAGE; MORTALITY; ADULTS; PROGNOSIS; PROPOFOL; BRAIN; NO AB Status epilepticus (SE) treatment ranges from small benzodiazepine doses to coma induction. For some SE subgroups, it is unclear how the risk of an aggressive therapeutic approach balances with outcome improvement. We recently developed a prognostic score (Status Epilepticus Severity Score, STESS), relying on four outcome predictors (age, history of seizures, seizure type and extent of consciousness impairment), determined before treatment institution. Our aim was to assess whether the score might have a role in the treatment strategy choice. This cohort study involved adult patients in three centers. For each patient, the STESS was calculated before primary outcome assessment: survival vs. death at discharge. Its ability to predict survival was estimated through the negative predictive value for mortality (NPV). Stratified odds ratios (OR) for mortality were calculated considering coma induction as exposure; strata were defined by the STESS level. In the observed 154 patients, the STESS had an excellent negative predictive value (0.97). A favorable STESS was highly related to survival (P < 0.001), and to return to baseline clinical condition in survivors (P < 0.001). The combined Mantel-Haenszel OR for mortality in patients stratified after coma induction and their STESS was 1.5 (95 % CI: 0.59-3.83). The STESS reliably identifies SE patients who will survive. Early aggressive treatment could not be routinely warranted in patients with a favorable STESS, who will almost certainly survive their SE episode. A randomized trial using this score would be needed to confirm this hypothesis. C1 [Rossetti, Andrea O.] CHUV BH07, Serv Neurol, CH-1011 Lausanne, Switzerland. [Logroscino, Giancarlo] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Milligan, Tracey A.; Bromfield, Edward B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Michaelides, Costas] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ruffieux, Christiane] CHU Vaudois, Inst Social & Prevent Med, CH-1011 Lausanne, Switzerland. [Ruffieux, Christiane] Univ Lausanne, Lausanne, Switzerland. RP Rossetti, AO (reprint author), CHUV BH07, Serv Neurol, 1011 Lausanne, CH-1011 Lausanne, Switzerland. EM andrea.rossetti@chuv.ch RI LOGROSCINO, GIANCARLO/K-5148-2016; Rossetti, Andrea/A-6712-2008 OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Rossetti, Andrea/0000-0002-7878-172X NR 30 TC 80 Z9 84 U1 0 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD OCT PY 2008 VL 255 IS 10 BP 1561 EP 1566 DI 10.1007/s00415-008-0989-1 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 372BY UT WOS:000260877600018 PM 18769858 ER PT J AU Tabrizi, S Craufurd, D Durr, A Fox, N Frost, C Hicks, S Illmann, T Johnson, H Kennard, C Landwehrmeyer, GB Langbehn, D AF Tabrizi, S. Craufurd, D. Durr, A. Fox, N. Frost, C. Hicks, S. Illmann, T. Johnson, H. Kennard, C. Landwehrmeyer, G. B. Langbehn, D. CA Track -HD Investigat TI Track-HD tracking progression in premanifest and early Huntington's disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT 5th Annual Meeting of the European Huntingtons Disease CY SEP 05-06, 2008 CL Lisbon, PORTUGAL SP European Huntingtons Dis Network C1 [Tabrizi, S.; Fox, N.] Inst Neurol, London WC1N 3BG, England. [Craufurd, D.] Univ Manchester, Manchester M13 9PL, England. [Durr, A.] Grp Hosp Pitie Salpetriere, F-75651 Paris 13, France. [Frost, C.] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. [Hicks, S.; Kennard, C.] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. [Landwehrmeyer, G. B.] Univ Ulm, D-89081 Ulm, Germany. [Langbehn, D.] Univ Iowa, Iowa City, IA USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Munster, D-48129 Munster, Germany. Leiden Univ, Med Ctr, NL-2300 RC Leiden, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Charlestown, MA 02130 USA. Monash Univ, Clayton, Vic 3800, Australia. RI Craufurd, David/G-5277-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD OCT 1 PY 2008 VL 79 SU 1 BP A19 EP A19 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 341PC UT WOS:000258725400059 ER PT J AU Youn, DH Wang, HB Jeong, SJ AF Youn, Dong-ho Wang, Haibin Jeong, Sung-Jin TI Exogenous tumor necrosis factor-alpha rapidly alters synaptic and sensory transmission in the adult rat spinal cord dorsal horn SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE tumor necrosis factor-alpha; spinal cord; substantia gelatinosa; synaptic transmission ID LONG-TERM POTENTIATION; NF-KAPPA-B; TNF-ALPHA; NEUROPATHIC PAIN; NERVE LIGATION; SCIATIC-NERVE; ROOT GANGLION; INCREASED SENSITIVITY; P38 MAPK; NEURONS AB The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is involved in the generation of inflammatory and neuropathic pain. This study investigated if TNF-alpha has any effect on spinal synaptic and/or sensory transmission by using whole-cell recordings of substantia gelatinosa (SG) neurons in transverse lumbar spinal cord slices of adult rats and by using behavioral tests. After intrathecal administration of TNF-alpha in adult rats, spontaneous hind paw withdrawal behavior and thermal hyperalgesia were rapidly induced (similar to 30 min), while mechanical allodynia slowly developed. Bath application of TNF-alpha (0.1-1 nM, 8 min) depressed peak amplitude of monosynaptic A delta and C fiber-evoked excitatory postsynaptic currents (EPSCs) without changing in holding currents and input resistances, whereas this application generally potentiated polysynaptic A delta fiberevoked EPSCs. Moreover, the frequencies, but not the amplitudes, of spontaneous and miniature EPSCs and spontaneous inhibitory postsynaptic currents were significantly increased by bath-applied TNF-alpha in most of the SG neurons. The effects of TNF-alpha on A delta/C fiberevoked monosynaptic and polysynaptic or spontaneous EPSCs were significantly blocked by 5 mu M TNF-alpha antagonist that inhibits TNF-alpha binding to its type 1 receptor (TNFR1). Because this study also found high protein expression of TNFR1 in the adult dorsal root ganglion and no change of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) induced whole-cell currents by TNF-alpha, we conclude that presynaptic TNFR1 at A delta/C primary afferent terminals contributes to the rapid alteration of synaptic transmission in the spinal SG, and the development of abnormal pain hypersensitivity by exogenous TNF-alpha. (C) 2008 Wiley-Liss, Inc. C1 [Youn, Dong-ho] Kyungpook Natl Univ, Brain Sci & Engn Inst, Taegu 700412, South Korea. [Youn, Dong-ho] Kyungpook Natl Univ, Dept Oral Physiol, Sch Dent & Brain Korea 21, Taegu 700412, South Korea. [Youn, Dong-ho; Wang, Haibin; Jeong, Sung-Jin] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Gr, Charlestown, MA USA. [Youn, Dong-ho; Wang, Haibin; Jeong, Sung-Jin] Harvard Univ, Sch Med, Charlestown, MA USA. RP Youn, DH (reprint author), Kyungpook Natl Univ, Sch Dent, Dept Oral Physiol, 188-1 Samdeok 2, Taegu 700412, South Korea. EM dyoun@knu.ac.kr FU Kyungpook National University Hospital FX We thank Dr. C. J. Woolf for useful comments and experimental Support; Drs. J. Scholz, T. Kohno, and D. Broom for comments and technical advice; and S.-M. Han for helping with the TNF-alpha antagonist experiment. This work was supported by a BioMedical Research Institute grant, Kyungpook National University Hospital (to D.Y. since 2007). NR 53 TC 42 Z9 47 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT PY 2008 VL 86 IS 13 BP 2867 EP 2875 DI 10.1002/jnr.21726 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 356PU UT WOS:000259790900007 PM 18543334 ER PT J AU Lu, HF Wei, GW Wang, DM Yung, P Ying, WH AF Lu, Huafei Wei, Gangwei Wang, Dongmin Yung, Patrick Ying, Weihai TI Posttreatment with the Ca(2+)-Mg(2+)-dependent endonuclease inhibitor aurintricarboxylic acid abolishes genotoxic agent-induced nuclear condensation and DNA fragmentation and decreases death of astrocytes SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE DNA fragmentation; nuclear condensation; cell death; Ca(2+)-Mg(2+) -endonucleases; astrocyte ID PROGRAMMED CELL-DEATH; NEURONAL DEATH; POLY(ADP-RIBOSE) POLYMERASE-1; APOPTOSIS; DAMAGE; ACTIVATION; ISCHEMIA; NECROSIS; NAD(+); DIFFERENTIATION AB DNA fragmentation and nuclear condensation are important nuclear changes in apoptosis. In this study we determined whether DNA fragmentation and nuclear condensation occur in astrocytes treated with 100-200 mu M of the genotoxic agent M-nitroso-N-nitroguanidine (MNNG). Our study also investigated the roles of Ca(2+) -Mg(2+) -dependent endonuclease (CME) in the MNNG-induced nuclear changes. We found that MNNG induced profound ATP depletion as well as marked nuclear condensation and DNA fragmentation in the cells. Both the nuclear condensation and the DNA fragmentation were abolished by posttreatment of the cells with the CME inhibitor aurintricarboxylic acid (ATA). The ATA posttreatment also significantly, but only partially, decreased MNNG-induced cell death. In contrast, pretreatment plus cotreatment with ATA did not affect either MNNG-induced nuclear condensation or cell death. Our study further suggests that ATA does not decrease the cytotoxicity of MNNG by directly inhibiting poly(ADPribose) polymerases. Collectively, our observations suggest that MNNG can induce both DNA fragmentation and nuclear condensation in astrocytes by a CME-dependent mechanism, which partially contributes to the genotoxic agent-induced cell death. Published 2008 Wiley-Liss, Inc. C1 Univ Calif San Francisco, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, Dept Neurol, San Francisco, CA USA. RP Ying, WH (reprint author), Vet Adm Med Ctr, Dept Neurol 127, 4150 Clement St, San Francisco, CA 94121 USA. EM weihai.ying@ucsf.edu FU VA MREP Award; Department of Defense; American Heart Association FX Contract grant sponsor: VA MREP Award; Contract grant sponsor: Department of Defense; Contract grant sponsor: American Heart Association (to W.Y.). NR 38 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT PY 2008 VL 86 IS 13 BP 2925 EP 2931 DI 10.1002/jnr.21733 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 356PU UT WOS:000259790900013 PM 18506851 ER PT J AU Lee, SM Manley, B AF Lee, Susan M. Manley, Bessie TI Nurse Director Rounds to Ensure Service Quality SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID HEALTH-CARE; MANAGERS C1 [Manley, Bessie] Massachusetts Gen Hosp, Surg Unit, Boston, MA 02114 USA. [Lee, Susan M.] Munn Ctr Nursing Res, Boston, MA USA. RP Manley, B (reprint author), Massachusetts Gen Hosp, Surg Unit, Phillips House 22,55 Fruit St, Boston, MA 02114 USA. EM bmanley1@partners.org NR 19 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD OCT PY 2008 VL 38 IS 10 BP 435 EP 440 DI 10.1097/01.NNA.0000338155.02730.0d PG 6 WC Nursing SC Nursing GA 369AK UT WOS:000260664700006 PM 18849748 ER PT J AU Lee, JS Gonzalez, ML Chuang, SK Perrott, DH AF Lee, Janice S. Gonzalez, Martin L. Chuang, Sung-Kiang Perrott, David H. TI Comparison of methohexital and propofol use in ambulatory procedures in oral and maxillofacial surgery SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID OUTPATIENT ANESTHESIA; CONSCIOUS SEDATION; INFUSION; SAFETY; OFFICE; REMIFENTANIL; INDUCTION; RECOVERY; FENTANYL AB Purpose: Short-acting anesthetic agents, such its propofol and methohexital. are commonly used for ambulatory procedures in the practices of Oral and maxillofacial surgeons (OMS). This study compares the safety and anesthetic outcomes of propofol and methohexital. In addition, the study compares the safety and outcomes of these agents when administered either by an OMS Who simultaneously, provides anesthesia and performs the procedure (anesthetist/surgeon), or by a non-OMS provider of anesthesia (anesthesiologist or certified registered nurse anesthetist; CRNA) whose sole obligation is to provide anesthesia. Materials and Methods: This is a prospective study of anesthesia techniques used in an office-based ambulatory setting by OMS throughout the United States, in which either propofol or methohexital was used for sedation/anesthesia. The study variables included demographic information, anesthetic agent, adverse outcomes related to anesthesia, operative procedure, and provider of anesthesia. These variables were compared with the patient group that received a benzodiazepine/narcotics regimen for sedation (control group). Bivariate (contingency tables) and multivariate (logistic regression) analyses were conducted. P <= .05 was considered statistically significant. Results: The study included 47,7 10 patients who met the inclusion criteria: 26,147 (54.8%) patients were in the propolol group, 15,859 (33.2%) were ill the methohexital group, and 5,704 (12.0%) were in the benzodiazepine group. Among all study patients, 333 (0.7%) had an adverse event. The most common complication was nausea and vomiting without aspiration. Of the patients ill the propolol group), methohexital group, or benzodiazepine group, 0.4%, 1.1%, and 0.8% had an adverse event, respectively. The higher number of complications among patients in the methohexital group compared with patients in the other 2 groups was statistically significant. Of 26,147 patients in the propolol group, 23,799 (91.0%) received anesthesia from an anesthetist/surgeon (OMS), and 2,368 (9.1%) from an anesthesiologist or nurse anesthetist (non-OMS). A total of 109 patients (0.4%) had an adverse event. The majority of patients who received anesthesia from a non-OMS were in the propofol group (2,368 of 2,404 patients; 98.5%). There was no statistically significant difference in the occurrence of adverse outcomes when comparing patients in the propofol group who received anesthesia front an OMS with those who received anesthesia from a non-OMS (P = .24, bivariate analysis. P = .33, multivariate analysis). Conclusions: There is I statistically significant increase ill adverse events related to methohexital compared with propofol or benzodiazepine/narcotics for anesthesia. Propofol appears to have the lowest risk for adverse events. There is no statistically significant difference in the number of adverse Outcomes between the administration of propofol for ambulatory surgery by OMS as an anesthetist/surgeon and anesthesiologist/nurse anesthetist. It remains critical that Our specialty maintains the highest standards, to provide safe anesthesia and to reduce adverse anesthetic events. (C) 2008 American Association of Oral and Maxillofacial Surgeons. C1 [Lee, Janice S.] Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. [Perrott, David H.] Amer Assoc Oral & Maxillofacial Surg, Outcomes Comm, Rosemont, IL USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Perrott, David H.] Salinas Valley Mem Healthcare Syst, Med Affairs, Salinas, CA 93901 USA. RP Perrott, DH (reprint author), Salinas Valley Mem Healthcare Syst, Med Affairs, 450 E Romie Lane, Salinas, CA 93901 USA. EM dperrott@svmh.com NR 31 TC 10 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD OCT PY 2008 VL 66 IS 10 BP 1996 EP 2003 DI 10.1016/j.joms.2008.06.028 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 355QL UT WOS:000259723300004 PM 18848094 ER PT J AU Shine, KM Spector, M AF Shine, Kristy M. Spector, Myron TI The presence and distribution of lubricin in the caprine intervertebral disc SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE lubricin; caprine intervertebral disc ID SUPERFICIAL ZONE PROTEIN; GENE-EXPRESSION; ARTICULAR-CARTILAGE; REGIONAL-VARIATIONS; ANNULUS FIBROSUS; SURFACE MOTION; PROTEOGLYCAN-4 PRG4; MOLECULAR-STRUCTURE; ANULUS FIBROSUS; SYNOVIAL-FLUID AB Lubricin is a large, multifunctional glycoprotein that is known to play a role as a boundary lubricant in diarthrodial joint articulation. The hypothesis of this study was that lubricin is present in the intervertebral disc in a distribution consistent with serving to facilitate interlamellar tribology. The objectives were to: (1) determine the distribution of lubricin in the normal caprine disc; and (2) investigate the synthesis of lubricin by caprine annulus fibrosus (AF) and nucleus pulposus (NP) cells in vitro, using immunohistochemical methods. Caprine lumbar intervertebral discs from five levels and four animals were studied. Positive staining revealed the presence of the lubricin in the outer AF of nearly all samples. No staining was present in the inner AF or the NP. Within the outer AF, lubricin was prominent in the layers separating lamellae and in the extracellular matrix of the lamellae. Some of the AF cells within the lubricin-positive regions demonstrated intracellular lubricin staining, suggesting that these cells may be synthesizing the lubricin protein observed. Immunohistochemistry performed on monolayer cultures of primary AF and NP cells demonstrated intracellular lubricin staining in both cell types. Thus, lubricin is selectively present in the outer caprine intervertebral disc AF, and its distribution suggests that it may play a role in interlamellar tribology. Cells from both the annulus and nucleus were found capable of synthesizing lubricin in vitro, suggesting that these cells may be a potential source of the glycoprotein under some conditions. (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 [Shine, Kristy M.; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. [Shine, Kristy M.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Shine, Kristy M.; Spector, Myron] Harvard MIT, Div Hlth Sci & Technol, Boston, MA 02115 USA. [Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Shine, KM (reprint author), VA Boston Healthcare Syst, Tissue Engn, 150 S Huntington Ave,MS 151, Boston, MA 02130 USA. EM shine@fas.harvard.edu FU Office of Research and Development; Rehabilitation Research and Development Service; Department of Veterans Affairs; National Science Foundation Fellowship; VA Research Career Scientist Awardee FX This work was supported by the Office of Research and Development, Rehabilitation Research and Development Service. Department of Veterans Affairs. KS was supported by a National Science Foundation Fellowship. MS is a VA Research Career Scientist Awardee. The authors are grateful to T.M. Schmid, Rush University Medical Center, for providing the lubricin antibody and for helpful discussions and to Alix Weaver for assistance in the laboratory. NR 52 TC 22 Z9 22 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD OCT PY 2008 VL 26 IS 10 BP 1398 EP 1406 DI 10.1002/jor.20614 PG 9 WC Orthopedics SC Orthopedics GA 351ZR UT WOS:000259465300015 PM 18464265 ER PT J AU de Witte, PB Lozano-Calderon, S Harness, N Watchmaker, G Green, MS Ring, D AF de Witte, Pieter Bas Lozano-Calderon, Santiago Harness, Neil Watchmaker, Greg Green, Michael S. Ring, David TI Acute vascular injury associated with fracture of the distal radius: A report of 6 cases SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE distal radius fracture; arterial injury ID ARTERY PSEUDOANEURYSM; FOREARM; PLATE; MULTICENTER; MANAGEMENT; FIXATION; REPAIR; HAND AB Objectives: To highlight the potential for vascular injury with fracture of the distal radius. Design: Retrospective case series. Setting: The practices of several orthopaedic hand surgeons Patients/Participants: Six patients with arterial injury as a consequence of fracture of the distal radius: 2 partial lacerations of the radial artery, 2 complete arterial lacerations (1 radial and 1 ulnar), 1 thrombosed radial artery, and 1 thrombosed ulnar artery. There were 4 men and 2 women with an average age of 42 years (range 26-70 years). Three of the fractures were open, and 3 had an associated distal ulnar fracture. Intervention: Volar open reduction and internal fixation of the distal radius fracture. Ligation or no treatment for 3 arterial injuries and repair or vein graft reconstruction (I patient) for 3 injuries. Main Outcome Measurements: Vascular status of the hand. Results: At an average follow-up of 9 months (range 5-16 months), all patients had a well-vascularized hand, normal capillary refill, and no complaints of vascular dysfunction. Conclusions: Vascular complications, once thought rare in association with fracture of the distal radius, may be more frequently recognized as volar exposures are increasingly used. Because most single artery injuries in the wrist and forearm are not associated with ischemia, identification of these injuries is unlikely to affect the functional result or outcome. In the unusual patient with a dysvascular hand after distal radius fracture, arterial reconstruction may be necessary. C1 [de Witte, Pieter Bas; Lozano-Calderon, Santiago] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Unit, Boston, MA 02114 USA. [Harness, Neil] Orange Cty Dept Orthopaed Surg, So Calif Permanente Med Grp, Irvine, CA USA. [Watchmaker, Greg] Milwaukee Hand Ctr, St Lukes Med Ctr, Milwaukee, WI USA. [Green, Michael S.] Lexington Med Ctr, Columbia, SC USA. [Ring, David] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Unit, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 25 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD OCT PY 2008 VL 22 IS 9 BP 611 EP 614 PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 357FG UT WOS:000259831100004 PM 18827590 ER PT J AU Compton, PA Wu, SM Schieffer, B Pham, Q Naliboff, BD AF Compton, Peggy A. Wu, Stephen M. Schieffer, Beatrix Pham, Quvnh Naliboff, Bruce D. TI Introduction of a self-report version of the prescription drug use questionnaire and relationship to medication agreement noncompliance SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE chronic nonmalignant pain; opioid medications; substance use disorder; problematic opioid use and/or misuse; medication agreements ID CHRONIC PAIN PATIENTS; NONMALIGNANT PAIN; OPIOID THERAPY; NEUROPATHIC PAIN; SUBSTANCE-ABUSE; ADDICTION; MANAGEMENT; EFFICACY; VALIDATION; MISUSE AB The Prescription, Drug Use Questionnaire (PDUQ) is one of several published tools developed to help clinicians better identify the presence of opioid abuse or dependence in patients with chronic pain. This paper introduces a patient version of the PDUQ (PDUQp), a 31-item questionnaire derived from the items of the original tool designed for self-administration, and describes evidence for its validity and reliability in a sample of patients with chronic nonmalignant pain and on opioid therapy. Further, this study examines instances of discontinuation from opioid medication treatment related to violation of the medication agreement in this population, and the relationship of these with problematic opioid misuse behaviors, PDUQ and PDUQp scores. A sample of 135 consecutive patients with chronic nonmalignant pain was recruited from a multidisciplinary Veterans Affairs chronic pain clinic, and prospectively followed over one year of opioid therapy. Using the PDUQ as a criterion measure, moderate to good concurrent and predictive validity data for the PDUQp are presented, as well as item-by-item comparison of the two formats. Reliability data indicate moderate test stability over time. Of those patients whose opioid treatment was discontinued due to medication agreement violation-related discontinuation (MAVRD) (n = 38 or 28% of sample), 40% of these (n = 11) were due to specific problematic opioid misuse behaviors. Based upon specificity and sensitivity analyses, a suggested cutoff PDUQp score for predicting MAVRD is provided. This study supports the PDUQp as a useful tool for assessing and predicting problematic opioid medication use in a chronic pain patient sample. C1 [Compton, Peggy A.] Univ Calif Los Angeles, Sch Nursing, Acute Care Sect, Los Angeles, CA 90095 USA. [Wu, Stephen M.; Schieffer, Beatrix; Pham, Quvnh; Naliboff, Bruce D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Wu, Stephen M.; Schieffer, Beatrix; Naliboff, Bruce D.] Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90024 USA. [Pham, Quvnh] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Naliboff, Bruce D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Compton, PA (reprint author), Univ Calif Los Angeles, Sch Nursing, Acute Care Sect, Factor Bldg 4-246,Box 956918, Los Angeles, CA 90095 USA. EM pcompton@sonnet.ucla.edu FU VA Health Services Research and Development FX This work was supported by VA Health Services Research and Development. NR 44 TC 34 Z9 34 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD OCT PY 2008 VL 36 IS 4 BP 383 EP 395 DI 10.1016/j.jpainsymman.2007.11.006 PG 13 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 360SP UT WOS:000260078300006 PM 18508231 ER PT J AU Goldsmith, B Dietrich, J Du, QL Morrison, RS AF Goldsmith, Benjamin Dietrich, Jessica Du, Qingling Morrison, R. Sean TI Variability in Access to Hospital Palliative Care in the United States SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE; END; HOME AB Background: Hospital palliative care programs provide high-quality, comprehensive care for seriously ill patients and their families. Objective: To examine geographic variation in patient and medical trainee access to hospital palliative care and to examine predictors of these programs. Methods: Primary and secondary analyses of national survey and census data. Hospital data including hospital palliative care programs were obtained from the American Hospital Association (AHA) Annual Survey Database (TM) for fiscal year 2006 supplemented by mailed surveys. Medical school-affiliated hospitals were obtained from the American Association of Medical Colleges, Web-site review, and telephone survey. Health care utilization data were obtained from the Dartmouth Atlas of Health Care 2008. Multivariate logistic regression was used to identify characteristics significantly associated with the presence of hospital palliative care. Results: A total of 52.8% of hospitals with 50 or more total facility beds reported hospital palliative care with considerable variation by state; 40.9% (144/352) of public hospitals, 20.3% (84/413) of for-profit hospitals, and 28.8% (160/554) of Medicare sole community providers reported hospital palliative care. A total of 84.5% of medical schools were associated with at least one hospital palliative care program. Factors significantly associated (p < 0.05) with hospital palliative care included geographic location, owning a hospice program, having an American College of Surgery approved cancer program, percent of persons in the county with a university education, and medical school affiliation. For-profit and public hospitals were significantly less likely to have hospital palliative care when compared with nonprofit institutions. States with higher hospital palliative care penetration rates were observed to have fewer Medicare hospital deaths, fewer intensive care unit/cardiac care unit (ICU/CCU) days and admissions during the last 6 months of life, fewer ICU/CCU admission during terminal hospitalizations, and lower overall Medicare spending/enrollee. Discussion: This study represents the most recent estimate to date of the prevalence of hospital palliative care in the United States. There is wide geographic variation in access to palliative care services although factors predicting hospital palliative care have not changed since 2005. Overall, medical students have high rates of access to hospital palliative care although complete penetration into academic settings has not occurred. The association between hospital palliative care penetration and lower Medicare costs is intriguing and deserving of further study. C1 [Morrison, R. Sean] Mt Sinai Sch Med, Dept Geriatr & Med, Brookdale Dept Geriatr & Adult Dev, New York, NY 10029 USA. [Goldsmith, Benjamin; Morrison, R. Sean] Natl Palliat Care Res Ctr, New York, NY USA. [Dietrich, Jessica] Ctr Adv Palliat Care, New York, NY USA. [Morrison, R. Sean] James J Peters Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Morrison, RS (reprint author), Mt Sinai Sch Med, Dept Geriatr & Med, Brookdale Dept Geriatr & Adult Dev, New York, NY 10029 USA. EM sean.morrison@mssm.edu FU National Palliative Care Research Center; Center to Advance Palliative Care; National Institute on Aging [K24 AG022345]; Olive Branch Foundations FX This study was supported by the National Palliative Care Research Center and the Center to Advance Palliative Care. Dr. Morrison is the recipient of a mid-career investigator award in patient oriented research from the National Institute on Aging (K24 AG022345). Mr. Goldsmith is a Doris Duke Clinical Research Fellow.; The Center to Advance Palliative Care and the National Palliative Care Research Center are supported by the Aetna, Brookdale, John A. Hartford, Jeht, Robert Wood Johnson, Emily Davie and Joseph S. Kornfeld, and Olive Branch Foundations. NR 13 TC 92 Z9 93 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD OCT PY 2008 VL 11 IS 8 BP 1094 EP 1102 DI 10.1089/jpm.2008.0053 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 372QZ UT WOS:000260917800011 PM 18831653 ER PT J AU Blanco, CL Falck, A Green, BK Cornell, JE Gong, AK AF Blanco, Cynthia Lidmilla Falck, Alison Green, Belinda Kay Cornell, John E. Gong, Alice Kim TI Metabolic Responses to Early and High Protein Supplementation in a Randomized Trial Evaluating the Prevention of Hyperkalemia in Extremely Low Birth Weight Infants SO JOURNAL OF PEDIATRICS LA English DT Article ID INTRAVENOUS AMINO-ACIDS; PRETERM INFANTS; INSULIN; LIFE AB Objective To determine whether early and higher intravenous amino acid (EHAA) supplementation decreases hyperkalemia in extremely low birth weight (ELBW) infants (<1000 g). Study design infants were enrolled at birth in a randomized, double-masked, prospective fashion and treated for 7 days. The standard group (SAA) infants received intravenous aminoacid (AA) starting at 0.5 g.kg(-1).d(-1) laid increased by 0.5 g.kg(-1).d(-1) every day to a maximum of 3 g.kg(-1).d(-1). EHAA group infants received 2 g.kg(-1).d(-1) of AA soon after birth and advanced by 1 g.kg(-1).d(-1) every day to 4 g.kg(-1).d(-1). Data analysis was by SPSS 11.5, with statistical significance at alpha = 0.05 and 90% power to determine a difference in mean K+ level of 2. Results Sixty-two patients, mean gestational age of 26.0 +/- 2.0 weeks and birth weight of 775 +/- 136 g, were enrolled. Hyperkalemia (K+ >= 6.5 mEq/L) occurred in 13% of the studied population; no difference in incidence of hyperkalemia was found between the SAA and EHAA groups (16% vs 10%. respectively, P = .70). Serum blood urea nitrogen was higher in the EHAA group. AA infusion was stopped early in 6 patients for high blood urea nitrogen or elevated ammonia level. Conclusions During the study period, hyperkalemia decreased significantly and was not affected by EHAA supplementation in the first week of life. C1 [Blanco, Cynthia Lidmilla; Gong, Alice Kim] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. [Green, Belinda Kay] Univ Hlth Syst, Dept Pharm, San Antonio, TX USA. [Cornell, John E.] S Texas Vet Hlth Care Syst, Dept Epidemiol & Biostat, San Antonio, TX USA. [Falck, Alison] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. RP Blanco, CL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, 7703 Floyd Curl Dr,MSC 7812, San Antonio, TX 78229 USA. EM blanco@uthscsa.edu NR 23 TC 28 Z9 33 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD OCT PY 2008 VL 153 IS 4 BP 535 EP 540 DI 10.1016/j.jpeds.2008.04.059 PG 6 WC Pediatrics SC Pediatrics GA 361BD UT WOS:000260101600021 PM 18589451 ER PT J AU Ghali, S Knox, KR Verbesey, J Scarpidis, U Izadi, K Ganchi, PA AF Ghali, S. Knox, K. R. Verbesey, J. Scarpidis, U. Izadi, K. Ganchi, P. A. TI Effects of lidocaine and epinephrine on cutaneous blood flow SO JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY LA English DT Article DE Cutaneous blood flow; Lidocaine; Epinephrine; Laser Doppler ID PREEMPTIVE LOCAL ANALGESIA; VAGINAL HYSTERECTOMY; PLASTIC-SURGERY; SKIN; PAIN; TEMPERATURE; UTILITY; NECK AB Background: Local anaesthetic agents in combination with epinephrine are frequently used in Local reconstructive procedures such as skin tumour excision and Local. flap closure. The purpose of this study was to measure the effect of subdermal injection of Lidocaine combined with epinephrine on cutaneous blood flow in the forearm and in the face. Methods: Thirty injections were performed on the forearm and 40 injections were performed on the face in five healthy volunteers. In both anatomical regions, 0.9% phosphate buffered saline (PBS) was used as a control, and experimental injections included 1% Lidocaine either alone or in combination with 1:100000 epinephrine, and an additional combination of 1% lidocaine with 1:200000 epinephrine used in the facial experiments. Cutaneous blood flow was measured indirectly using Laser Doppler imaging (moorLDI(TM)-Mark 2). Results: A statistically significant increase in blood flow was achieved with injection of Lidocaine in the forearm compared to saline, whereas a non-statistically significant increase was achieved with saline injection compared to lidocaine in the face. This occurred in the first 5 min in the forearm and 2 min in the face. The addition of 1:100000 epinephrine to lidocaine resulted in an immediate decrease in cutaneous blood flow which was maximal at 10 min in the forearm and 8 min in the face. This was statistically significant compared to all other injections except for the combination of 1:200000 epinephrine with lidocaine, injected in the face. Conclusions: The vascularity of different anatomical areas may account for blood flow differences following injection with saline and lidocaine. Incisions should be delayed for 10 min in the forearm and 8 min in the face following lidocaine + epinephrine injection to allow maximal benefit to take effect. There were no significant differences between 1:100000 and 1:200000 epinephrine combined with lidocaine in facial injections his study. (C) 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. C1 [Ganchi, P. A.] Ganchi Plast Surg, Wayne, NJ 07470 USA. [Ghali, S.; Knox, K. R.] NYU, Lab Microvasc Res & Vasc Tissue Engn, New York, NY USA. [Verbesey, J.] Massachusetts Gen Hosp, Dept Plast Surg, Boston, MA 02114 USA. [Scarpidis, U.; Izadi, K.] Univ Med & Dent New Jersey, Div Plast Surg, Newark, NJ 07103 USA. RP Ganchi, PA (reprint author), Ganchi Plast Surg, 342 Hamburg Turnpike,Suite 202, Wayne, NJ 07470 USA. EM info@ganchi.com NR 18 TC 16 Z9 18 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1748-6815 J9 J PLAST RECONSTR AES JI J. Plast. Reconstr. Aesthet. Surg. PD OCT PY 2008 VL 61 IS 10 BP 1226 EP 1231 DI 10.1016/j.bjps.2007.09.011 PG 6 WC Surgery SC Surgery GA 362XK UT WOS:000260230300020 PM 17980687 ER PT J AU Pollack, MH Endicott, J Liebowitz, M Russell, J Detke, M Spann, M Ball, S Swindle, R AF Pollack, Mark H. Endicott, Jean Liebowitz, Michael Russell, James Detke, Michael Spann, Melissa Ball, Susan Swindle, Ralph TI Examining quality of life in patients with generalized anxiety disorder: Clinical relevance and response to duloxetine treatment SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article; Proceedings Paper CT 27th Annual Conference of the Anxiety-Disorders-Association-of-America CY MAR 29-APR 01, 2007 CL St Louis, MO SP Anxiety Disorders Assoc Amer DE quality of life; generalized anxiety disorder; duloxetine; clinical relevance ID PRIMARY-CARE; MAJOR DEPRESSION; IMPAIRMENT; INTERVIEW; SCALE; DISABILITY; REMISSION; PLACEBO; IMPACT; STATES AB Background: Duloxetine, a serotonergic noradrenergic reuptake inhibitor, improved functional outcomes in each of three clinical studies for the treatment of adults with generalized anxiety disorder (GAD). Using comparison norms, the current work describes the clinical relevance of these functional improvements in terms of return to normative functioning and symptom remission. Methods: Data were pooled at the individual patient level from three double-blind, placebo-controlled trials of duloxetine treatment (9-10 weeks acute therapy, dose ranges 60-120 mg). Inclusion/exclusion criteria were consistent across studies, and outcome measures included the Sheehan Disability Scale (SDS), Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), and European Quality of Life 5 Dimensions (EQ-5D). Results: Adult patients (mean age = 42.4 years; 65% women) were randomly assigned to duloxetine (N = 668) or placebo (N = 495). At baseline, the majority of patients were impaired on the SDS global functioning (89%), Q-LES-Q-SF maximum percent (95%), and EQ-5D (76%) scores. On each measure, a greater percentage of duloxetine-treated patients converted from an impaired baseline to a normative endpoint score than did placebo-treated patients (p <= 0.001, all comparisons). Remission defined as a HAMA total score at endpoint of <= 10, compared with <= 7, captured a greater proportion of patients who were functionally in remission. Conclusions: GAD is associated with substantial impairment in functioning and subjective well-being, and patients treated with duloxetine 60-120 mg/day, compared with placebo, experienced a greater return to normative functioning. Attention to role functioning and quality of life may refine our definition of remission when using standard symptom measures of anxiety. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Pollack, Mark H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Endicott, Jean; Liebowitz, Michael] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA. [Russell, James; Detke, Michael; Spann, Melissa; Ball, Susan; Swindle, Ralph] Lilly Res Labs, Indianapolis, IN USA. [Detke, Michael] Harvard Univ, Sch Med, McLean Hosp, Boston, MA 02115 USA. [Detke, Michael; Ball, Susan] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. RP Pollack, MH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,185 Cambridge St,Suite 2200,2nd, Boston, MA 02114 USA. EM mpollack@partners.org NR 33 TC 28 Z9 30 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2008 VL 42 IS 12 BP 1042 EP 1049 DI 10.1016/j.jpsychires.2007.11.006 PG 8 WC Psychiatry SC Psychiatry GA 350GG UT WOS:000259340100010 PM 18221755 ER PT J AU Yehuda, R Bell, A Bierer, LM Schmeidler, J AF Yehuda, Rachel Bell, Amanda Bierer, Linda M. Schmeidler, James TI Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE parental PTSD; maternal PTSD; intergenerational transmission of trauma; Holocaust survivors; depressive disorder; prevalence ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; FAMILIAL PSYCHIATRIC-ILLNESS; AUSTRALIAN VIETNAM VETERANS; MAJOR DEPRESSIVE DISORDER; PITUITARY-ADRENAL AXIS; WORLD-WAR-II; SURVEY REPLICATION; PARENTAL PTSD; SECONDARY TRAUMATIZATION AB Background: A significant association between parental PTSID and the occurrence of PTSD in offspring has been noted, consistent with the idea that risk for the development of PTSD is transmitted from parent to child. Two recent reports linking maternal PTSD and low offspring cortisol prompted us to examine the relative contributions of maternal vs. paternal PTSD in the prediction of PTSD and other psychiatric diagnoses in offspring. Methods: One hundred seventeen men and 167 women, recruited from the community, were evaluated using a comprehensive psychiatric battery designed to identify traumatic life experiences and lifetime psychiatric diagnoses. 211 of these subjects were the adult offspring of Holocaust survivors and 73 were demographically comparable Jewish controls. Participants were further subdivided based on whether their mother, father, neither, or both parents met diagnostic criteria for lifetime PTSD. Results: A higher prevalence of lifetime PTSD, mood, anxiety disorders, and to a lesser extent, substance abuse disorders, was observed in offspring of Holocaust survivors than controls. The presence of maternal PTSD was specifically associated with PTSD in adult offspring of Holocaust Survivors. However, other psychiatric diagnoses did not show specific effects associated with maternal PTSD. Conclusion: The tendency for maternal PTSD to make a greater contribution than paternal PTSD to PTSD risk suggests that classic genetic mechanisms are not the sole model of transmission, and paves way for the speculation that epigenetic factors may be involved. In contrast, PTSD in any parent contributes to risk for depression, and parental traumatization is associated with increased anxiety disorders in offspring. Published by Elsevier Ltd. C1 Mt Sinai Sch Med, Traumat Stress Studies Div, Bronx, NY 10468 USA. James J Peters Vet Affairs Med Ctr, OOMH, Bronx, NY 10468 USA. RP Yehuda, R (reprint author), Bronx Vet Affairs Med Ctr, Psychiat OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Ritchel.Yehuda@va.gov FU NCRR NIH HHS [5 M01 RR00071]; NIMH NIH HHS [R01 MH064675, R01 MH064675-01, R01 MH064675-02, R01 MH064675-03, R01 MH064675-04, R01 MH064675-05, R01 MH64675-01] NR 49 TC 98 Z9 101 U1 8 U2 28 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2008 VL 42 IS 13 BP 1104 EP 1111 DI 10.1016/j.jpsychires.2008.01.002 PG 8 WC Psychiatry SC Psychiatry GA 351JL UT WOS:000259420500007 PM 18281061 ER PT J AU Pollack, MH Kornstein, SG Spann, ME Crits-Christoph, P Raskin, J Russell, JM AF Pollack, Mark H. Kornstein, Susan G. Spann, Melissa E. Crits-Christoph, Paul Raskin, Joel Russell, James M. TI Early improvement during duloxetine treatment of generalized anxiety disorder predicts response and remission at endpoint SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Generalized anxiety disorder; Duloxetine; Early improvement; Remission ID COMORBIDITY SURVEY REPLICATION; DSM-IV DISORDERS; PANIC DISORDER; DRUG-TREATMENT; PREVALENCE; DISABILITY; DEPRESSION; PLACEBO; BURDEN; PHARMACOTHERAPY AB Because many patients do not respond to pharmacotherapy for generalized anxiety disorder (GAD), it would be beneficial to know if early response is predictive of final outcome so that timely clinical decisions can be made about augmentation or alternative treatments. This topic has not been examined with the now recommended first-line treatments (selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors) for GAD. Combined data from three 9 to 10 week acute treatment, multi-center, randomized, placebo-controlled studies of duloxetine for GAD were used to explore early improvement on the Hamilton Anxiety Rating Scale (HAMA) in relation to endpoint HAMA response (>= 50% improvement from baseline), HAMA remission (<= 7), Clinical Global Impression-Improvement (CGI-1) response (<= 2), and functional remission as measured by the Sheehan Disability Scale Global Functional Improvement (<= 5). For duloxetine-treated patients (n = 668), the relationships between the proportion of patients who achieved each category of early (week 2 and week 4) HAMA improvement (>= 20%, >= 40%, >= 60%, and >= 80%) and achievement of endpoint HAMA response, HAMA remission, CGI response, and SDS remission status were all statistically significant (all P's <= 0.003). One hundred percent of the duloxetine-treated patients who showed substantial HAMA improvement (>80%) at week 2, and 93% at week 4, were HAMA responders at endpoint. At week 2, 79% of the duloxetine-treated patients who achieved a HAMA improvement of 40-59% were HAMA responders at endpoint. About half of duloxetine-treated patient showing 40-59% early HAMA improvement were remitters on the SDS at endpoint. These data suggest a connection between early improvement and endpoint response and remission status that can be used to guide clinical decision-making. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Pollack, Mark H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Kornstein, Susan G.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Spann, Melissa E.; Russell, James M.] Lilly Res Labs, Indianapolis, IN USA. [Crits-Christoph, Paul] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Raskin, Joel] Lilly Res Labs, Toronto, ON, Canada. RP Pollack, MH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,185 Cambridge St,Suite 2200,2nd, Boston, MA 02114 USA. EM mpollack@partners.org FU Eli Lilly; Boehringer Ingelheim GmbH FX Financial support was provided by Eli Lilly and Boehringer Ingelheim GmbH. The authors acknowledge Janelle Erickson PhD, Steve Gelwicks MS, Christine Young MS, Wenqi You MS, and Nicholas Okopokho MS, for statistical support. NR 35 TC 25 Z9 28 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2008 VL 42 IS 14 BP 1176 EP 1184 DI 10.1016/j.jpsychires.2008.02.002 PG 9 WC Psychiatry SC Psychiatry GA 369AY UT WOS:000260666200005 PM 18348888 ER PT J AU Hadlock, TA Cheney, ML AF Hadlock, Tessa A. Cheney, Mack L. TI Single-Incision Endoscopic Sural Nerve Harvest for Cross Face Nerve Grafting SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE Endoscopic nerve harvest; sural nerve ID FACIAL PARALYSIS AB Cross face nerve grafting followed by free muscle transfer has become a standard of care in rehabilitation of the paralyzed face. In an effort to address the surgical morbidity of sural nerve harvest, multiple groups have attempted to minimize lower extremity trauma from sural nerve harvest. In very preliminary studies, investigators have adapted the use of vein harvesting equipment for harvest of the sural nerve. In this article we describe the use of endoscopic vein harvesting equipment for sural nerve harvest in a series of eight patients undergoing facial reanimation, in which a single distal incision is made posterior to the lateral malleolus. Eight patients presented for first-stage cross face nerve grafting for facial reanimation over a 6-month period. Each patient was operated on using a two-team approach. One team exposed the donor branches of the facial nerve on the healthy side while the endoscopic harvest was simultaneously executed in the lower limb by the second team. In each case, the sural nerve graft > 20 cm in length was removed through a single 1.5-cm incision. There were no complications. Operative tines decreased steadily throughout the period examined and were < 20 minutes for the last two patients. For the final two cases, a modified sural nerve stripper was introduced through the instrument portal of the VasoView device (Guidant Co., Natick, MA), which contained a small notch through which the nerve could be threaded, greatly facilitating dissection. This contributed to decreasing operative times. Thus we combined the technological advances of a sophisticated endoscopic system with our minimally invasive nerve stripper technique to improve sural nerve harvest. We found no increased morbidity from the endoscopic approach, and in all cases we were able to remove the nerve through a single incision. The endoscopic sural nerve harvest is an excellent addition to the armamentarium of the facial reanimation surgeon. C1 [Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Dept Otolaryngol Head & Neck Surg, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. [Hadlock, Tessa A.; Cheney, Mack L.] Harvard Univ, Sch Med, Boston, MA USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Dept Otolaryngol Head & Neck Surg, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 17 TC 5 Z9 5 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD OCT PY 2008 VL 24 IS 7 BP 519 EP 523 DI 10.1055/s-0028-1088235 PG 5 WC Surgery SC Surgery GA 363FR UT WOS:000260253700009 PM 18798144 ER PT J AU Hula, SNA Robin, DA Maas, E Ballard, KJ Schmidt, RA AF Hula, Shannon N. Austermann Robin, Donald A. Maas, Edwin Ballard, Kirrie J. Schmidt, Richard A. TI Effects of Feedback Frequency and Timing on Acquisition, Retention, and Transfer of Speech Skills in Acquired Apraxia of Speech SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE apraxia of speech; apraxia treatment; feedback; principles of motor learning ID GENERALIZED MOTOR PROGRAM; LEARNING CONCEPTS; SCHEMA THEORY; KNOWLEDGE; APHASIA; DELAY; SCHEDULES; STROKE; ADULTS AB Purpose: Two studies examined speech skill learning in persons with apraxia of speech (AOS). Motor-learning research shows that delaying or reducing the frequency of feedback promotes retention and transfer of skills. By contrast, immediate or frequent feedback promotes temporary performance enhancement but interferes with retention and transfer. These principles were tested in the context of a common treatment for AOS. Method: Two studies (N = 4, N = 2) employed single-subject treatment designs to examine acquisition and retention of speech skills in adults with AOS under different feedback conditions. Results: Reduced-frequency or delayed feedback enhanced learning in 3 participants with AOS. Feedback manipulation was not an influential variable in 3 other cases in which stimulus-complexity effects may have masked treatment effects. Conclusions: These findings demonstrate that individuals with AOS can benefit from structured intervention. They provide qualified support for reduction and delay of feedback, although interaction with other factors such as stimulus complexity or task difficulty needs further exploration. This study adds to the growing body of literature investigating the use of principles of motor learning in treating AOS and provides impetus for consideration of pre-treatment variables that affect outcome in treatment studies. C1 [Hula, Shannon N. Austermann; Robin, Donald A.; Maas, Edwin] San Diego State Univ, San Diego, CA 92182 USA. [Hula, Shannon N. Austermann; Robin, Donald A.; Maas, Edwin] Univ Calif San Diego, La Jolla, CA 92093 USA. [Ballard, Kirrie J.] Univ Iowa, Iowa City, IA USA. [Schmidt, Richard A.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Hula, SNA (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. EM shannon.hula@va.gov RI Robin, Donald/F-2109-2010; Ballard, Kirrie/F-9558-2011; OI Ballard, Kirrie/0000-0002-9917-5390 NR 62 TC 26 Z9 26 U1 5 U2 21 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD OCT 1 PY 2008 VL 51 IS 5 BP 1088 EP 1113 DI 10.1044/1092-4388(2008/06-0042) PG 26 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 357SD UT WOS:000259865700003 ER PT J AU Ghosh, SS Tourville, JA Guenther, FH AF Ghosh, Satrajit S. Tourville, Jason A. Guenther, Frank H. TI A Neuroimaging Study of Premotor Lateralization and Cerebellar Involvement in the Production of Phonemes and Syllables SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE speech motor control; cerebellum; Broca's area; hemispheric asymmetry; region-of-interest analysis; sparse clustered imaging; syllable production ID EVENT-RELATED FMRI; SURFACE-BASED ANALYSIS; VERBAL WORKING-MEMORY; HUMAN AUDITORY-CORTEX; HUMAN VISUAL-CORTEX; BASAL GANGLIA; FUNCTIONAL MRI; MOTOR CORTEX; SPEECH ARTICULATION; ATAXIC DYSARTHRIA AB Purpose: This study investigated the network of brain regions involved in overt production of vowels, monosyllables, and bisyllables to test hypotheses derived from the Directions Into Velocities of Articulators (DIVA) model of speech production (Guenther, Ghosh,& Tourville, 2006). The DIVA model predicts left lateralized activity in inferior frontal cortex when producing a single syllable or phoneme and increased cerebellar activity for consonant-vowel syllables compared with steady-state vowels. Method: Sparse sampling functional magnetic resonance imaging (fMRI) was used to collect data from 10 right-handed speakers of American English while producing isolated monosyllables (e.g., "ba," "oo"). Data were analyzed using both voxel-based and participant-specific anatomical region-of-interest-based techniques. Results: Overt production of single monosyllables activated a network of brain regions, including left ventral premotor cortex, left posterior inferior frontal gyrus, bilateral supplementary motor area, sensorimotor cortex, auditory cortex, thalamus, and cerebellum. Paravermal cerebellum showed greater activity for consonant-vowel syllables compared to vowels. Conclusions: The finding of left-lateralized premotor cortex activity supports the DIVA model prediction that this area contains cell populations representing syllable motor programs without regard for semantic content. Furthermore, the superior paravermal cerebellum is more active for consonant-vowel syllables compared with vowels, perhaps due to increased timing constraints for consonant production. C1 [Ghosh, Satrajit S.] MIT, Speech Commun Grp, Elect Res Lab, Cambridge, MA 02139 USA. [Ghosh, Satrajit S.; Tourville, Jason A.; Guenther, Frank H.] Boston Univ, Boston, MA 02215 USA. [Guenther, Frank H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Ghosh, SS (reprint author), MIT, Speech Commun Grp, Elect Res Lab, Room 36-547,50 Vassar St, Cambridge, MA 02139 USA. EM satra@mit.edu OI Ghosh, Satrajit/0000-0002-5312-6729 FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIDCD NIH HHS [R01 DC002852-13, R01 DC001925, R01 DC001925-14, R01 DC002852, R01 DC01925, R01 DC02852] NR 88 TC 63 Z9 64 U1 0 U2 8 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD OCT 1 PY 2008 VL 51 IS 5 BP 1183 EP 1202 DI 10.1044/1092-4388(2008/07-0119) PG 20 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 357SD UT WOS:000259865700010 PM 18664692 ER PT J AU Grikscheit, TC Sala, FG Ogilvie, J Bower, KA Ochoa, ER Alsberg, E Mooney, D Vacanti, JP AF Grikscheit, Tracy C. Sala, Frederic G. Ogilvie, Jennifer Bower, Kate A. Ochoa, Erin R. Alsberg, Eben Mooney, David Vacanti, Joseph P. TI Tissue-engineered spleen protects against overwhelming pneumococcal sepsis in a rodent model SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE tissue engineering; tissue-engineered intestine; tissue-engineered spleen; solid organ tissue engineering; overwhelming postsplenectomy sepsis; pneumococcal sepsis ID POSTSPLENECTOMY INFECTION; SMALL-INTESTINE; TRANSPLANTATION; REGENERATION; SPLENECTOMY; TRAUMA; COLON AB Background/Purpose. Solid organs production is an ultimate goal of tissue engineering. After refining a technique for intestinal engineering, we applied it to a solid organ, the spleen. Overwhelming postsplenectomy sepsis results in death in nearly half of all cases. This risk is pronounced in children. Necrosis of autotransplanted spleen slices occurs prior to regeneration. We postulate that tissue engineering techniques might be superior. Methods. Four groups of Lewis rats were compared: sham laparotomy, tissue-engineered spleen (TES), traditional spleen slices, and splenectomy. TES was generated from splenic units, multicellular components of juvenile spleen implanted on a biodegradable polymer scaffold, and spleen slices were derived from age-matched juveniles. Pneumococcal sepsis was induced at wk 16, and survival curves were constructed. Results. Tissue-engineered spleen protected against pneumococcal septicemia with a survival proportion of 85.7% compared with 41.17% of splenectomized animals. Spleen slice was also protective with 71.43% survival. Compared with splenectomy, control and TES groups were statistically significant (P = 0.0002, P = 0.0087; hazard ratio of splenectomy = 5.493) and the Slice group was nearly statistically significant (P 0.0642, hazard ratio of splenectomy = 2.673). Conclusions. TES is a novel application of tissue engineering to splenic regeneration and creates a functional spleen. This approach could be advantageous in severe pediatric trauma. (c) 2008 Elsevier Inc. All rights reserved. C1 [Grikscheit, Tracy C.; Sala, Frederic G.] Childrens Hosp Los Angeles, Dept Surg, Los Angeles, CA 90027 USA. [Grikscheit, Tracy C.; Sala, Frederic G.] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA. [Ogilvie, Jennifer] Univ Pittsburgh, Dept Surg, Med Ctr, Pittsburgh, PA USA. [Bower, Kate A.] CS Motts Childrens Hosp, Dept Pediat, Ann Arbor, MI USA. [Ochoa, Erin R.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA. [Alsberg, Eben] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Alsberg, Eben] Case Western Reserve Univ, Dept Orthopaed Surg, Cleveland, OH 44106 USA. [Mooney, David] Harvard Univ, Dept Engn & Appl Sci, Boston, MA 02115 USA. [Vacanti, Joseph P.] MassGen Hosp Children, Dept Surg, Boston, MA USA. RP Grikscheit, TC (reprint author), Childrens Hosp Los Angeles, Dept Surg, 4650 Sunset Blvd Mailstop 100, Los Angeles, CA 90027 USA. EM tgrikscheit@chla.usc.edu FU Center for the Integration of Medicine and Innovation in Technology, Department of Defense [DAMDIT-99-2-9001] FX This study was funded by the Center for the Integration of Medicine and Innovation in Technology, Department of Defense DAMDIT-99-2-9001. NR 23 TC 14 Z9 14 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2008 VL 149 IS 2 BP 214 EP 218 DI 10.1016/j.jss.2008.01.01.0 PG 5 WC Surgery SC Surgery GA 350DG UT WOS:000259332200008 PM 18621401 ER PT J AU Sano, Y Gomez, FE Hermsen, JL Kang, W Lan, JG Maeshima, Y Kudsk, KA AF Sano, Yoshifumi Gomez, F. Enrique Hermsen, Joshua L. Kang, Woodae Lan, Jinggang Maeshima, Yoshinori Kudsk, Kenneth A. TI Parenteral nutrition induces organ specific alterations in polymeric immunoglobulin receptor levels SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE immunoglobulin A; polymeric immunoglobulin receptor; mucosal immunity; parenteral nutrition ID UPPER RESPIRATORY-TRACT; MUCOSAL IMMUNITY; ABDOMINAL-TRAUMA; LYMPHOID-TISSUE; SECRETORY IGA; FED MICE; ROUTE; MOUSE; EXPRESSION; INTESTINE AB Background. Secretory immunoglobulin A (IgA) prevents pathogen adherence at mucosal surfaces to prevent infection. Polymeric immunoglobulin receptor (pIgR), located on the basolateral. surface of mucosal cells, binds dimeric IgA produced by B cells with the cooperation of T cells in the lamina propria. This IgA-pIgR complex is transported apically, where it is exocytosed as secretory IgA to the mucosal surface. Our prior work shows that parenteral nutrition (PN) impairs both airway and small intestine mucosal immunity by reducing T and B cells and IgA levels. This work examines intestinal and respiratory tissue-specific pIgR responses to PN. Methods. Cannulated male Institute of Cancer Research mice were randomized to Chow (n = 10) or PN (n = 10). After 5 days, animals were sacrificed and lavages obtained from the small intestine, lung (BAL = bronchoalveolar lavage), and nasal airways (NAL). Small intestine, lung, and nasal passage tissues were also collected. Lavage and tissue homogenate IgA levels were quantified by enzyme-linked immunosorbent assay and pIgR by Western blot. Results. PN group SIL and NAL IgA levels dropped significantly compared with Chow. PN significantly reduced pIgR levels in the SI while no pIgR change was noted in nasal passages and lung pIgR actually increased with PN. Tissue homogenate IgA levels did not change with PN in the SI while levels in the nasal passage and lung decreased. Conclusions. PN impairs airway mucosal immunity by reduction in IgA available for transport rather than via a reduction in pIgR levels. In the small intestine, diminished pIgR is implicated in the deterioration of antibody-mediated mucosal immunity. (c) 2008 Elsevier Inc. All rights reserved. C1 [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. [Sano, Yoshifumi; Gomez, F. Enrique; Hermsen, Joshua L.; Kang, Woodae; Lan, Jinggang; Maeshima, Yoshinori; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. [Sano, Yoshifumi] Jikei Univ, Dept Surg, Sch Med, Tokyo, Japan. RP Kudsk, KA (reprint author), Univ Wisconsin Hosp & Clin, H4-736 CSC,600 Highland Ave, Madison, WI 53792 USA. EM KUDSK@surgery.wisc.edu FU NIH [R01 GM53439] FX The authors acknowledge support by NIH grant R01 GM53439; also based upon work supported in part by the Office of Research and Development, Biomedical Laboratory R and D Service, Department of Veterans Affairs. The authors thank the Yakult Central Institute for Microbiological Research for providing the SC antibody. NR 37 TC 14 Z9 15 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2008 VL 149 IS 2 BP 236 EP 242 DI 10.1016/j.jss.2007.12.790 PG 7 WC Surgery SC Surgery GA 350DG UT WOS:000259332200011 PM 18599079 ER PT J AU Farrow, B Albo, D Berger, DH AF Farrow, Buckminster Albo, Daniel Berger, David H. TI The role of the tumor microenvironment in the progression of pancreatic cancer SO JOURNAL OF SURGICAL RESEARCH LA English DT Review DE pancreatic cancer; tumor microenvironment; review; pancreatic stellate cells; perineural invasion; tumor stroma ID GROWTH-FACTOR RECEPTOR; EXTRACELLULAR-MATRIX PROTEINS; HUMAN PROSTATE-CANCER; PLASMINOGEN-ACTIVATOR SYSTEM; CELL INVASION; STELLATE-CELLS; TGF-BETA; PERINEURAL INVASION; DUCTAL CARCINOMA; GENE-EXPRESSION AB Pancreatic cancer is the most lethal abdominal malignancy due to its aggressive growth and rapid development of distant metastases, thus making treatment extremely difficult. Additionally, pancreatic adenocarcinoma is locally invasive, surrounded by a dense desmoplastic reaction which can involve adjacent vital structures, limiting the number of patients who are candidates for surgical resection at the time of diagnosis. Recently the tumor microenvironment in other adenocarcinomas has been determined to be an important mediator of cancer cell behavior; however, few studies have elucidated the tumor-stroma interactions in pancreatic cancer. This review summarizes the role of pancreatic stellate cells, perineural. invasion, angiogenesis, and inflammatory cells in fostering pancreatic cancer cell growth and invasion. The importance of extracellular matrix proteins, growth factors, and cytokines is also presented. Finally we suggest ideas for new avenues of research into the pancreatic tumor microenvironment which may permit the development of novel, more effective treatments for pancreatic cancer. (c) 2008 Elsevier Inc. All rights reserved. C1 [Farrow, Buckminster; Albo, Daniel; Berger, David H.] Baylor Coll Med, Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Farrow, B (reprint author), Baylor Coll Med, Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM bfarrow@bcm.edu NR 110 TC 88 Z9 93 U1 4 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2008 VL 149 IS 2 BP 319 EP 328 DI 10.1016/j.jss.2007.12.7157 PG 10 WC Surgery SC Surgery GA 350DG UT WOS:000259332200021 PM 18639248 ER PT J AU Kidd, G Richards, VM Mason, CR Gallun, FJ Huang, R AF Kidd, Gerald, Jr. Richards, Virginia M. Mason, Christine R. Gallun, Frederick J. Huang, Rong TI Informational masking increases the costs of monitoring multiple channels SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID UNCERTAIN FREQUENCY; SIGNAL-DETECTION; MASKERS AB This study examined the costs of simultaneously monitoring two frequency regions. Listeners detected low- and high-frequency tones in a 2I4AFC procedure. On every trial, each signal was presented in either the first or second interval independently. Comparison of thresholds in single- and dual-signal conditions provided an estimate of the costs. Thresholds were obtained in quiet, in notched-filtered noise, and in randomized multitone maskers. No cost was found in quiet, whereas large costs were found for the masked conditions, especially for the multitone masker. These results suggest that costs of dividing attention in frequency depend on both signal and non-signal channels. (C) 2008 Acoustical Society of America C1 [Kidd, Gerald, Jr.; Mason, Christine R.] Boston Univ, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA. [Kidd, Gerald, Jr.; Mason, Christine R.] Boston Univ, Ctr Hearing Sci, Boston, MA 02215 USA. [Richards, Virginia M.; Huang, Rong] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Gallun, Frederick J.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. RP Kidd, G (reprint author), Boston Univ, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA. EM gkidd@bu.edu; richards@psych.uppen.edu; cmason@bu.edu; frederick.gallun@va.gov; rongh@sas.upenn.edu RI Gallun, Frederick/G-3792-2012 OI Gallun, Frederick/0000-0002-4145-2199 FU AFOSR [FA9550-05-1-2005]; NIH/NIDCD [DC004545, DC02012]; NIDCD [F32 DC006526] FX This work was supported by AFOSR Award No. FA9550-05-1-2005 and by Grant No. DC004545 and DC02012 from NIH/NIDCD. EG. was supported by F32 DC006526 from NIDCD. NR 14 TC 5 Z9 6 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 2008 VL 124 IS 4 BP EL223 EP EL229 DI 10.1121/1.2968302 PN 1 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 363WQ UT WOS:000260298600058 PM 19062790 ER PT J AU Sena, MJ Utter, GH Cuschieri, J Maier, RV Tompkins, RG Harbrecht, BG Moore, EE O'Keefe, GE AF Sena, Matthew J. Utter, Garth H. Cuschieri, Joseph Maier, Ronald V. Tompkins, Ronald G. Harbrecht, Brian G. Moore, Ernest E. O'Keefe, Grant E. TI Early Supplemental Parenteral Nutrition Is Associated with Increased Infectious Complications in Critically ill Trauma Patients SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID STANDARD OPERATING PROCEDURES; SCALE COLLABORATIVE PROJECT; ORIENTED RESEARCH CORE; INTENSIVE-CARE-UNIT; CLINICAL CARE; HOST RESPONSE; INTRAVENOUS FAT; MECHANICAL VENTILATION; ENTERAL NUTRITION; SURGICAL PATIENTS AB BACKGROUND: Parenteral nutrition (PN) is often used in severely injured patients when caloric goals are not achieved enterally. The purpose of this Study is to determine whether early administration of parenteral nutrition is associated with an increased risk for infection after severe injury. STUDY DESIGN: Retrospective cohort study of severely injured blunt trauma patients enrolled from eight trauma centers participating in the "Inflammation and the Host Response to Injury" (Glue Grant) study. We compared patients receiving PN within 7 days after injury with a control group that did not receive early PN. We then focused on patients who tolerated at least some enteral nutrition (EN) during the first week and evaluated the potential influence of Supplemental PN on outcomes in this "enteral tolerant" subgroup. Primary outcomes included occurrence of a nosocomial infection after the first postinjury week. Secondary outcomes included type of infection and hospital mortality. RESULTS: Of 567 patients enrolled, 95 (17%) received early PN. Early PN use was associated with a greater risk of nosocomial infection (relative risk [RR] = 2.1; 95% CI, 1.6 to 2.6; p < 0.001). In the enteral-tolerant Subgroup (n = 249), early PN was also associated with an increase in nosocomial infections (RR = 1.6; 95% CI, 1.2 to 2.1; p = 0.005) in part because of an increased risk of bloodstream infection (RR = 2.8; 95% CI, 1.5 to 5.3; p = 0.002). Mortality tended to be higher in patients receiving additional EN and PN versus EN alone (RR = 2.3; 95% Cl, 1.0 to 5.2; p = 0.06). CONCLUSIONS: In critically ill trauma patients who are able to tolerate at least some EN, early PN administration can contribute to increased infectious morbidity and worse clinical outcomes. (J Am Coll Surg 2008;207:459-467. (C) 2008 by the American College of Surgeons) C1 [Sena, Matthew J.; Utter, Garth H.] Univ Calif Davis, Med Ctr, Dept Surg, Sacramento, CA 95817 USA. [Cuschieri, Joseph; Maier, Ronald V.; O'Keefe, Grant E.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. [Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Harbrecht, Brian G.] Univ Louisville, Dept Surg, Louisville, KY 40292 USA. [Moore, Ernest E.] Denver Hlth Med Ctr, Dept Surg, Denver, CO USA. RP Sena, MJ (reprint author), Univ Calif Davis, Med Ctr, Dept Surg, 2315 Stockton Blvd,Room 4206, Sacramento, CA 95817 USA. OI Utter, Garth/0000-0001-7747-3429 FU National Institute of General Medical Sciences [2-U54-GM062119] FX The Investigators acknowledge the contribution of the Inflammation and the Host Response to Injury Large-Scale Collaborative Project Award #2-U54-GM062119 from the National Institute of General Medical Sciences. NR 38 TC 36 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD OCT PY 2008 VL 207 IS 4 BP 459 EP 467 DI 10.1016/j.jamcollsurg.2008.04.028 PG 9 WC Surgery SC Surgery GA 363NM UT WOS:000260274000001 PM 18926446 ER PT J AU Bilimoria, KY Talamonti, MS Sener, SF Bilimoria, MM Stewart, AK Winchester, DP Ko, CY Bentrem, DJ AF Bilimoria, Karl Y. Talamonti, Mark S. Sener, Stephen F. Bilimoria, Malcolm M. Stewart, Andrew K. Winchester, David P. Ko, Clifford Y. Bentrem, David J. TI Effect of Hospital Volume on Margin Status after Pancreaticoduodenectomy for Cancer SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID LONG-TERM SURVIVAL; MINIMAL POSTOPERATIVE COMPLICATIONS; PANCREATIC-CANCER; PROGNOSTIC-FACTORS; RESECTABLE ADENOCARCINOMA; SURGEONS CONTRIBUTION; RESECTION MARGINS; DATA-BASE; OUTCOMES; HEAD AB BACKGROUND: The volume-outcome relationship has been repeatedly demonstrated for pancreatectomy, but identifying underlying reasons for this association has been challenging. Some have Suggested that differences in surgical technique may affect longterm survival, but it is unknown whether margin-positive resection rates vary by hospital Volume. Our objective was to evaluate the effect of hospital pancreatectomy Volume on margin status. STUDY DESIGN: Patients who underwent pancreaticoduodenectomy for localized pancreatic adenocarcinoma were identified from the National Cancer Data Base (1998 to 2004). Regression modeling adjusting for patient, tumor, and hospital factors was used to assess predictors of margin involvement and to evaluate the effect of margin status on survival. Volume quintiles were based on average annual hospital pancreatectomy Volume. RESULTS: Of 12,101 patients, 24.4% had positive resection margins (14.6% microscopic/R1; 9.8% macroscopic/R2). From 1998 to 2004, there was nor a significant change in margin-positive resection rates (p = 0.43). Oil multivariable analysis, patients were more likely to have a margin-positive resection if they had a higher T classification or nodal involvement, were uninsured or living in lower-incline areas, or underwent resection at lowest-volume hospitals compared with highest-volume hospitals (25.9% versus 22.6%, p < 0.0001; odds ratio, 1.21; 95% confidence interval, 1.01 to 1.43). On multivariable analysis, margin involvement was associated with a higher risk of longterm mortality compared with margin-negative resections (p < 0.0001). CONCLUSIONS: Involved resection margins are a poor prognostic factor after a pancreaticoduodenectomy. Patients undergoing pancreaticoduodenectomy at low-volume centers are more likely to have margin-positive resections. Standardization of pathologic evaluation for pancreatectomy specimens is needed. (J Am Coll Surg 2008;207:510-519. (C) 2008 by the American College of Surgeons) C1 [Bilimoria, Karl Y.; Stewart, Andrew K.; Winchester, David P.; Ko, Clifford Y.] Amer Coll Surg, Canc Program, Chicago, IL 60611 USA. [Bilimoria, Karl Y.; Talamonti, Mark S.; Sener, Stephen F.; Bilimoria, Malcolm M.; Winchester, David P.; Bentrem, David J.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Evanston, IL 60208 USA. [Talamonti, Mark S.; Sener, Stephen F.; Bilimoria, Malcolm M.; Winchester, David P.] Evanston NW Healthcare, Chicago, IL USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Canc Program, 633 N St Clair St,25th Floor, Chicago, IL 60611 USA. NR 55 TC 68 Z9 73 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD OCT PY 2008 VL 207 IS 4 BP 510 EP 519 DI 10.1016/j.jamcollsurg.2008.04.033 PG 10 WC Surgery SC Surgery GA 363NM UT WOS:000260274000007 PM 18926452 ER PT J AU Lamster, IB DePaola, DP Oppermann, RV Papapanou, PN Wilder, RS AF Lamster, Ira B. DePaola, Dominick P. Oppermann, Rui V. Papapanou, Panos N. Wilder, Rebecca S. TI The relationship of periodontal disease to diseases and disorders at distant sites Communication to health care professionals and patients SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE Periodontal diseases; health promotion; communication; oral health ID ADVERSE PREGNANCY OUTCOMES; LOW-BIRTH-WEIGHT; PRETERM BIRTH; DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; RHEUMATOID-ARTHRITIS; DENTAL-HEALTH; HEART-DISEASE; RISK; ASSOCIATION AB Background. The body of research defining relationships among periodontal disease and certain systemic diseases and disorders has been expanding, and questions have been raised regarding what information should be conveyed to health care professionals and patients. Methods. Representatives from dentistry, medicine, the academic community and the insurance industry convened a two-day workshop July 23 and 24, 2007. Results. The workshop participants achieved general consensus on a number of issues, including the need for greater cooperation between the health care professions. This cooperation should translate into improved clinical care as physicians refer patients for dental care, and dentists are proactive in regard to the general health of their patients. Conclusion. Communication to health care professionals requires a multifaceted approach that includes publication of research findings in medical and dental journals, cooperation among professional organizations and initiatives at the local level such as presentations at; medical grand rounds. Dental schools should play a role in their health science centers. Communication with patients may improve through the use of targeted informational brochures in the offices of medical specialists, appropriate media campaigns and efforts led by local dental organizations. Practice Implications. It is too early to provide specific recommendations regarding the treatment of periodontal disease to improve specific health outcomes, but dentists can become advocates for a general health promotion and disease prevention message. The lifestyles approach includes an improved diet, smoking cessation, appropriate hygiene practices and stress reduction. These strategies can improve oral and general health outcomes. C1 [Lamster, Ira B.; Papapanou, Panos N.] Columbia Univ, Coll Dent Med, Sect Oral & Diagnost Sci, New York, NY 10032 USA. [Papapanou, Panos N.] Columbia Univ, Coll Dent Med, Div Periodont, New York, NY 10032 USA. [Wilder, Rebecca S.] Univ N Carolina, Sch Dent, Chapel Hill, NC USA. [Oppermann, Rui V.] Univ Fed Rio Grande do Sul, Sch Dent, Porto Alegre, RS, Brazil. [Oppermann, Rui V.] Univ Fed Rio Grande do Sul, Dept Periodontol, Porto Alegre, RS, Brazil. [DePaola, Dominick P.] Forsyth Inst, Boston, MA USA. [DePaola, Dominick P.] Nova SE Univ, Coll Dent Med, Ft Lauderdale, FL 33314 USA. RP Lamster, IB (reprint author), Columbia Univ, Coll Dent Med, Sect Oral & Diagnost Sci, 630 W 168th St, New York, NY 10032 USA. EM ibl1@columbia.edu FU Johnson & Johnson Consumer & Personal Products Worldwide; Division of Johnson & Johnson Group of Consumer Companies, New Brunswick, N.J. FX The workshop discussed in this study was sponsored by Johnson & Johnson Consumer & Personal Products Worldwide, a Division of Johnson & Johnson Group of Consumer Companies, New Brunswick, N.J. NR 58 TC 13 Z9 14 U1 1 U2 7 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 2008 VL 139 IS 10 BP 1389 EP 1397 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 361AO UT WOS:000260100100022 PM 18832275 ER PT J AU Hazzard, WR AF Hazzard, William R. TI Defining geriatrics to forge coalitions and gain leverage SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material C1 [Hazzard, William R.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Hazzard, William R.] VA Puget Sound Hlth Care Syst, Dept Geriatr & Extended Care, Seattle, WA USA. RP Hazzard, WR (reprint author), Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. EM william.ha-zzard@med.va.gov NR 9 TC 3 Z9 3 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2008 VL 56 IS 10 BP 1812 EP 1815 DI 10.1111/j.1532-5415.2008.02003.x PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 358EO UT WOS:000259900100005 PM 19054200 ER PT J AU Crnich, CJ Drinka, P AF Crnich, Christopher J. Drinka, Paul TI Treatment of Bacteriuria in Older Adults: Still Room for Improvement SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Editorial Material ID NURSING-HOME RESIDENTS; TERM-CARE FACILITIES; ASYMPTOMATIC BACTERIURIA; ANTIBIOTIC USE; EDUCATIONAL INTERVENTION; ANTIMICROBIAL USE; TRACT-INFECTIONS; PROCALCITONIN; TRIAL; PYELONEPHRITIS C1 [Crnich, Christopher J.] Univ Wisconsin, Dept Med, Infect Dis Sect, Sch Med & Publ Hlth, Madison, WI USA. [Crnich, Christopher J.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Drinka, Paul] Univ Wisconsin, Sch Med & Publ Hlth, Sect Geriatr, Madison, WI USA. [Drinka, Paul] Bethany Home, Waupaca, WI USA. RP Crnich, CJ (reprint author), 600 Highland Ave,CSC H4-557, Madison, WI 53792 USA. EM cjc@medicine.wisc.edu OI Crnich, Christopher/0000-0002-9320-9262 NR 31 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 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD OCT PY 2008 VL 9 IS 8 BP 542 EP 544 DI 10.1016/j.jamda.2008.07.004 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 362YN UT WOS:000260233200003 PM 19083286 ER PT J AU Buchanan, RJ Rosenthal, M Graber, DR Wang, SJ Kim, MS AF Buchanan, Robert J. Rosenthal, Mark Graber, David R. Wang, Suojin Kim, Myung Suk TI Racial and Ethnic Comparisons of Nursing Home Residents at Admission SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Nursing facilities; race; ethnicity; minorities; Minimum Data Set ID MINIMUM DATA SET; OLDER-ADULTS; CARE; HEALTH; DISPARITIES; POPULATION; PREDICTORS; DISEASE; HIV; MANAGEMENT AB Objective: To present racial/ethnic comparisons of comprehensive profiles of nursing home residents at admission, including whites, African Americans, Hispanics, Asians/Pacific Islanders, and American Indians/Alaska Natives. Methods: More than 885,000 admission assessments recorded in the national Minimum Data Set (MDS) were analyzed. Racial and ethnic analyses of the MDS admission assessments were conducted using the software package SAS. Results: There were significant racial/ethnic differences in gender and age, with minority residents more likely to be male and younger. African American, Hispanic, and Asian/Pacific Islanders were significantly more likely than white residents to exhibit total dependence in the self-performance of the ADLs and to have greater cognitive impairments, with Asian/Pacific Islanders the most physically dependent and cognitively impaired. Discussion: The results illustrate significant and substantive differences among the racial/ethnic groups for many demographic characteristics, as well as health-related indicators and conditions. This analysis suggests that the general perspective that economically disadvantaged minorities enter nursing homes in worse condition than whites is too simplistic. More research, particularly qualitative studies of specific minority groups, will advance our understanding of why members of some racial/ethnic groups require nursing home placement sooner than other groups. C1 [Buchanan, Robert J.] Mississippi State Univ, Dept Polit Sci & Publ Adm, Mississippi State, MS 39762 USA. [Rosenthal, Mark] Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA USA. [Rosenthal, Mark] W Los Angeles Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Los Angeles, CA 90073 USA. [Graber, David R.] Med Univ S Carolina, Dept Hlth Adm & Policy, Charleston, SC 29425 USA. [Wang, Suojin] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Kim, Myung Suk] Sogang Univ, Coll Business Adm, Seoul, South Korea. RP Buchanan, RJ (reprint author), Mississippi State Univ, Dept Polit Sci & Publ Adm, Mississippi State, MS 39762 USA. EM rjb161@ps.msstate.edu FU National Institute of Environmental Health Sciences [P30 ES09106] FX S.W.'s research was supported in part by the Texas A&M University Center for Environmental and Rural Health via a grant from the National Institute of Environmental Health Sciences (P30 ES09106) to do statistical methodology research and its applications to the health sciences. NR 53 TC 6 Z9 6 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD OCT PY 2008 VL 9 IS 8 BP 568 EP 579 DI 10.1016/j.jamda.2008.04.012 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 362YN UT WOS:000260233200008 PM 19083291 ER PT J AU Imam, SN Wright, K Bhoopalam, N Choudhury, A AF Imam, Syed Nasrat Wright, Khadijah Bhoopalam, Nimiala Choudhury, Abdul TI Hemolytic Anemia From Ceftriaxone in an Elderly Patient: A Case Report SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Ceftriaxone; hemolytic anemia; elderly ID IMMUNE HEMOLYSIS AB Hemolytic anemia is uncommon in the general population; however, drug-induced hemolysis is not rare in hospitalized patients. We report a case of unrecognized subacute hemolytic anemia due to ceftriaxone in a geriatric patient requiring multiple blood transfusions before a correct diagnosis could be established. This is a US government work. There are no restrictions on its use. C1 [Imam, Syed Nasrat; Wright, Khadijah] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Imam, Syed Nasrat; Wright, Khadijah; Bhoopalam, Nimiala; Choudhury, Abdul] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Imam, SN (reprint author), Loyola Univ, Med Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA. EM syed.imam@va.gov NR 3 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD OCT PY 2008 VL 9 IS 8 BP 610 EP 611 DI 10.1016/j.jamda.2008.05.001 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 362YN UT WOS:000260233200014 PM 19083297 ER PT J AU Scherrer-Crosbie, M Thibault, HB AF Scherrer-Crosbie, Marielle Thibault, Helene B. TI Echocardiography in translational research: Of mice and men SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE animal research; echocardiography; mice; myocardial function; myocardial perfusion ID NITRIC-OXIDE SYNTHASE; MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; COLOR DOPPLER-ECHOCARDIOGRAPHY; VENTRICULAR DIASTOLIC FUNCTION; DECREASES INFARCTION SIZE; CELL-ADHESION MOLECULE-1; CORONARY FLOW RESERVE; IN-VIVO; ULTRASOUND BIOMICROSCOPY; HEART-FAILURE AB Mice are increasingly used in cardiovascular research, and echocardiography is ideally suited to evaluate their cardiac phenotype. This review describes the current use of mice echocardiography and focuses on some of its applications in both basic and clinical science. C1 [Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com FU NCRR NIH HHS [S10 RR022586, S10 RR022586-01A1] NR 92 TC 27 Z9 27 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD OCT PY 2008 VL 21 IS 10 BP 1083 EP 1092 DI 10.1016/j.echo.2008.07.001 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 355II UT WOS:000259702200001 PM 18723318 ER PT J AU Tournoux, F Chan, RC Handschumacher, MD Salgo, IS Manzke, R Settlemier, S Guerrero, JL Cury, RC Weyman, AE Picard, MH AF Tournoux, Francois Chan, Raymond C. Handschumacher, Mark D. Salgo, Ivan S. Manzke, Robert Settlemier, Scott Guerrero, J. Luis Cury, Ricardo C. Weyman, Arthur E. Picard, Michael H. TI Estimation of radial strain and rotation using a new algorithm based on speckle tracking SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE echocardiography; speckle tracking; radial strain; rotation; phantom model ID ACUTE MYOCARDIAL-INFARCTION; 2-DIMENSIONAL STRAIN; ULTRASOUND METHOD; HEART-FAILURE; IN-VITRO; VALIDATION; ECHOCARDIOGRAPHY; DEFORMATION; INNER AB Background: The aim of this study was to test the ability of a new algorithm to accurately measure point-to-point Lagrangian strain (LS) and local rotation (ROT). Change in distance between 2 separate regions of interest (ROIs) can theoretically be computed with speckle tracking (SpT) and used to calculate LS in any tissue location with angle independence and high spatial resolution. Similarly, tracking an ROI relative to a fixed point should provide an estimate of ROT. Methods: Two dynamic phantoms (60 beats/min) were scanned in short axis at frame rates of 30, 60, and 90 Hz. To estimate LS, 2 ROIs were positioned immediately beneath the inner and outer borders of the superior wall of the first phantom and tracked using SpT. LS derived from SpT (SpT-LS) was compared with LS measured by sonomicrometers placed on the inner and outer walls of the phantom (SN-LS). To estimate ROT, the rotational vectors around the centroid of a second phantom were calculated for 3 epicardial bead targets imaged with gated computed tomography (CT) and compared with measurements derived from SpT. Results: There was a significant correlation between SpT-LS and SN-LS at 30 Hz (R-2 = 0.99; P <.0001), 60 Hz (R-2 = 0.98; P <.0001), and 90 Hz (R-2 = 0.99; P <.0001). There was also a significant correlation between ROT derived from SpT and ROT derived from CT: R-2 = 0.97 (P <.0001) at 30 Hz, R-2 = 0.95 (P <.0001) at 60 Hz, and R-2 = 0.98 (P <.0001) at 90 Hz. Conclusions: Point-to-point SpT permits the determination of LS between 2 distinct tissue regions as well as ROT measurement of specific tissue regions without the need for border detection. C1 [Tournoux, Francois] Univ Paris 07, Hop Lariboisiere, AP HP, Cardiac Ultrasound Lab, F-75010 Paris, France. [Tournoux, Francois; Handschumacher, Mark D.; Weyman, Arthur E.; Picard, Michael H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA USA. [Guerrero, J. Luis] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Surg Lab, Boston, MA USA. [Chan, Raymond C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Manzke, Robert; Cury, Ricardo C.] Massachusetts Gen Hosp, Clin Site, Philips Res North Amer, Boston, MA 02114 USA. [Salgo, Ivan S.; Settlemier, Scott] Philips Med Syst, Andover, MA USA. RP Tournoux, F (reprint author), Univ Paris 07, Hop Lariboisiere, AP HP, Cardiac Ultrasound Lab, 10 Rue Ambroise Pare, F-75010 Paris, France. EM ftournoux@gmail.com OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [5R01HL073647-05] NR 23 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD OCT PY 2008 VL 21 IS 10 BP 1168 EP 1174 DI 10.1016/j.echo.2008.06.004 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 355II UT WOS:000259702200014 PM 18672346 ER PT J AU Kottgen, A Hwang, SJ Rampersaud, E Coresh, J North, KE Pankow, JS Meigs, JB Florez, JC Parsa, A Levy, D Boerwinkle, E Shuldiner, AR Fox, CS Kao, WHL AF Kottgen, Anna Hwang, Shih-Jen Rampersaud, Evadnie Coresh, Josef North, Kari E. Pankow, James S. Meigs, James B. Florez, Jose C. Parsa, Afshin Levy, Daniel Boerwinkle, Eric Shuldiner, Alan R. Fox, Caroline S. Kao, W. H. Linda TI TCF7L2 variants associate with CKD progression and renal function in population-based cohorts SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; GENOME-WIDE ASSOCIATION; POLYCYSTIC KIDNEY-DISEASE; OLD ORDER AMISH; ATHEROSCLEROSIS RISK; INSULIN-RESISTANCE; DIABETES-MELLITUS; SERUM CREATININE; LINKAGE ANALYSIS; SHORT-TERM AB Genetic variants may increase susceptibility to both diabetes and kidney disease. Whether known diabetes-associated variants in the transcription factor 7-like 2 (TCF7L2) gene are associated with chronic kidney disease (CKD) progression and markers of kidney function is unknown. Participants of the Atherosclerosis Risk in Communities Study (ARIC; n = 11,061 self-identified white and n = 4014 black), Framingham Heart Offspring Cohort (FHS; n = 2468), and Heredity and Phenotype Intervention Heart Study (HAPI; n = 861) were genotyped at five (ARIC) and two (FHS) common TCF7L2 variants. The diabetes-conferring risk alleles at rs7903146 and rs7901695 were significantly associated with CKD progression among ARIC participants overall and among those without baseline diabetes. The overall adjusted hazard ratios per rs7903146 T allele were 1.17 (95% confidence interval [CI] 1.04 to 1.32) for white individuals and 1.20 (95% Cl 1.03 to 1.41) for black individuals. Similarly, the overall hazard ratios per rs7901695 C allele were 1.19 (95% Cl 1.06to 1.34) for white individuals and 1.27 (95% CI 1.09to 1.48) for black individuals. The FHS cohort supported these results: The rs7903146 T allele was significantly associated with lower estimated GFR (P = 0.01) and higher cystatin C (P = 0.004) in adjusted analyses overall and among those without diabetes. In the HAPI cohort, the rs7901695 C allele was significantly associated with lower estimated GFR in adjusted analyses (P = 0.049), as were several variants upstream and downstream of TCF7L2 (P < 0.003). No identified variant in the ARIC or FHS cohorts was associated with albuminuria. In conclusion, several population-based samples suggest that variants in the TCF7L2 gene are associated with reduced kidney function or CKD progression, overall and specifically among participants without diabetes. C1 [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Kottgen, Anna; Coresh, Josef; Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Rampersaud, Evadnie; Parsa, Afshin; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Meigs, James B.; Florez, Jose C.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov; wkao@jhsph.edu RI Kottgen, Anna/D-2920-2012; OI Pankow, James/0000-0001-7076-483X FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HC-25195]; National Institutes of Health (NIH)/NHLBI-sponsored National Research Service Award Institutional Training Grant in Cardiac and Vascular Cell Biology [T32HL072751]; NIH [U01 HL72515, K24 DK080140]; University of Maryland General Clinical Research Center [M01 RR 16500]; Johns Hopkins University General Clinical Research Center [M01 RR 000052]; Clinical Nutrition Research Unit of Maryland [P30 DK072488]; American Diabetes Association Research Award; ADA Career Development Award; NIH Research Career Award [K23 DK65978-03]; [1K12RR023250-01]; [K01DK067207] FX The ARIC Study was Supported by contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 with the National Heart, Lung, and Blood Institute (NHLBI). The FHS is Supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). The HAN Heart Study is Supported by the National Institutes of Health (NIH)/NHLBI-sponsored National Research Service Award Institutional Training Grant in Cardiac and Vascular Cell Biology T32HL072751, NIH research grant U01 HL72515, the University of Maryland General Clinical Research Center grant M01 RR 16500, the Johns Hopkins University General Clinical Research Center grant M01 RR 000052, and the Clinical Nutrition Research Unit of Maryland (P30 DK072488). A.K. is supported by an Get-man Research Foundation Fellowship. LB.M. is supported by an American Diabetes Association Research Award, an ADA Career Development Award, and NIH grant K24 DK080140. LCT. is supported by an NIH Research Career Award K23 DK65978-03. A.P. is supported by 1K12RR023250-01. W.H.K. is Supported by K01DK067207. NR 47 TC 24 Z9 24 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2008 VL 19 IS 10 BP 1989 EP 1999 DI 10.1681/ASN.2007121291 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 357FE UT WOS:000259830900020 PM 18650481 ER PT J AU Akins, CW Travis, B Yoganathan, AP AF Akins, Cary W. Travis, Brandon Yoganathan, Ajit P. TI Energy loss for evaluating heart valve performance SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID VENTRICULAR STROKE WORK; AORTIC-VALVE; PRESSURE RECOVERY; HYDRODYNAMIC FUNCTION; MITRAL REGURGITATION; STENOSIS SEVERITY; BILEAFLET VALVES; ORIFICE AREA; DOPPLER; PROSTHESES AB Energy loss is a well-established engineering concept that when applied to evaluating the performance of native heart valves and valvular prostheses has the potential for providing valuable information about the impact of valve function on myocardial performance. The concept has been understood for many years, but its routine application has been hindered not only by a lack of understanding of its meaning but also because of the lack of investigational tools to easily obtain the data necessary for its estimation. Today the gathering of that information is becoming easier, and thus the time has come to revisit the efficacy of energy loss for evaluating heart valve performance. This review defines what energy loss is, how it is measured, and how it might be applied to clinical situations of heart valve disease to better understand the impact of valvular disease on ventricular function. C1 [Akins, Cary W.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. [Travis, Brandon] Skejby Sygehus, T Forskning, DK-8200 Aarhus N, Denmark. [Yoganathan, Ajit P.] Georgia Inst Technol, Wallace H Coulter Sch Biomed Engn, Atlanta, GA 30332 USA. [Yoganathan, Ajit P.] Emory Univ, Atlanta, GA 30322 USA. RP Akins, CW (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Cox 648, Boston, MA 02114 USA. EM cakins@partners.org NR 36 TC 35 Z9 36 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD OCT PY 2008 VL 136 IS 4 BP 820 EP 833 DI 10.1016/j.jtcvs.2007.12.059 PG 14 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 364CW UT WOS:000260314800005 PM 18954618 ER PT J AU Heist, RS Fidias, P Huberman, M Ardman, B Sequist, LV Temel, JS Lynch, TJ AF Heist, Rebecca Suk Fidias, Panos Huberman, Mark Ardman, Blair Sequist, Lecia V. Temel, Jennifer S. Lynch, Thomas J. TI A Phase II Study of Oxaliplatin, Pemetrexed, and Bevacizumab in Previously Treated Advanced Non-small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol DE Non-small cell lung cancer; Oxaliplatin; Pemetrexed; Bevacizumab; Previously treated ID CHEMOTHERAPY; CARBOPLATIN; CISPLATIN; COMBINATION; PACLITAXEL; ERLOTINIB; TRIAL AB Introduction: Single agent chemotherapy is standard for second and third line treatment of non-small cell lung cancer (NSCLC). Combination therapy to date has not proven to be superior to single agents in this setting, often adding toxicity without any additional efficacy. We investigated the activity and tolerability of the combination of oxaliplatin, pemetrexed, and bevacizumab in patients with previously treated advanced NSCLC. Methods: This multicenter phase 11 trial evaluated the safety and efficacy of the combination of pemetrexed (500 Mg/m(2)), oxaliplatin (120 mg/m(2)), and bevacizumab (15 mg/kg), given every 21 days, in patients with previously treated advanced NSCLC. Eligibility criteria included performance status 0 to 1, nonsquamous histology, and at least one prior chemotherapy regimen. Patients with treated brain metastases were allowed. The primary end point was response rate, with secondary endpoints of progression-free Survival and overall survival. Results: Thirty-six patients were enrolled on this study. Treatment was well tolerated; the most common grade 3 toxicity was hypertension, which was easily managed with oral medications. The nine (25%) patients with treated brain metastases had no episodes of cerebral hemorrhage. Of the 34 patients evaluable for tumor response, none had complete response, nine (27%) had partial respouse, 15 (44%) had stable disease, and 10 (29%) had progressive disease. Median progression-free survival was 5.8 months (95% confidence interval 4.1-7.8 months) and median overall survival was 12.5 months (95% confidence interval 7.3-17 months). Conclusions: Treatment with oxaliplatin and pemetrexed in combination with the targeted antiangiogenic agent bevacizumab yielded promising efficacy with manageable toxicity in the previously treated advanced NSCLC population. C1 [Heist, Rebecca Suk; Fidias, Panos; Sequist, Lecia V.; Temel, Jennifer S.; Lynch, Thomas J.] Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, Boston, MA 02114 USA. [Huberman, Mark] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA USA. [Ardman, Blair] Lowell Gen Hosp, Div Hematol Oncol, Lowell, MA USA. RP Heist, RS (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, 32 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM rheist@partners.org NR 16 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD OCT PY 2008 VL 3 IS 10 BP 1153 EP 1158 DI 10.1097/JTO.0b013e318187273f PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 361KX UT WOS:000260127600011 PM 18827612 ER PT J AU Abel, GA Neufeld, EJ Sorel, M Weeks, JC AF Abel, G. A. Neufeld, E. J. Sorel, M. Weeks, J. C. TI Direct-to-consumer advertising for bleeding disorders: a content analysis and expert evaluation of advertising claims SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE bleeding disorder; direct-to-consumer advertising; health services; hemophilia ID PRESCRIPTION DRUG ADVERTISEMENTS; INFORMATION AB Objective: In the United States, the Food and Drug Administration (FDA) requires that all direct-to-consumer advertising (DTCA) contain both an accurate statement of a medication's effects ('truth') and an even-handed discussion of its benefits and risks/adverse effects ('fair balance'). DTCA for medications to treat rare diseases such as bleeding disorders is unlikely to be given high priority for FDA review. Methods: We reviewed all DTCA for bleeding disorder products appearing in the patient-directed magazine HemeAware from January 2004 to June 2006. We categorized the information presented in each advertisement as benefit, risk/adverse effect, or neither, and assessed the amount of text and type size devoted to each. We also assessed the readability of each type of text using the Flesch Reading Ease Score (FRES, where a score of >= 65 is considered of average readability), and assessed the accuracy of the advertising claims utilizing a panel of five bleeding disorder experts. Results: A total of 39 unique advertisements for 12 products were found. On average, approximately twice the amount of text was devoted to benefits as compared with risks/adverse effects, and the latter was more difficult to read [FRES of 32.0 for benefits vs. 20.5 for risks/adverse effects, a difference of 11.5 (95% CI: 4.5-18.5)]. Only about two-thirds of the advertising claims were considered by a majority of the experts to be based on at least low-quality evidence. Conclusion: As measured by our methods, print DTCA for bleeding disorders may not reach the FDA's standards of truth and fair balance. C1 [Abel, G. A.; Sorel, M.; Weeks, J. C.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Ctr Outcomes & Policy Res,Dept Med Oncol, Boston, MA 02115 USA. [Neufeld, E. J.] Harvard Univ, Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA. RP Abel, GA (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Ctr Outcomes & Policy Res,Dept Med Oncol, 44 Binney St,Smith 271, Boston, MA 02115 USA. EM gregory_abel@dfci.harvard.edu RI Neufeld, Ellis/F-9331-2011 FU National Heart Lung and Blood Institute (NHLBI) [HL004184] FX This project was funded in part by K24 grant HL004184 from the National Heart Lung and Blood Institute (NHLBI). NR 17 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD OCT PY 2008 VL 6 IS 10 BP 1680 EP 1684 DI 10.1111/j.1538-7836.2008.03083.x PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 350OK UT WOS:000259361900011 PM 18647231 ER PT J AU Sovershaev, MA Lind, KF Devold, H Jorgensen, TO Hansen, JB Osterud, B Egorina, EM AF Sovershaev, M. A. Lind, K. F. Devold, H. Jorgensen, T. O. Hansen, J. -B. Osterud, B. Egorina, E. M. TI No evidence for the presence of tissue factor in high-purity preparations of immunologically isolated eosinophils SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE eosinophils; immunologic purification; monocytes; tissue factor expression ID IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; PHORBOL-MYRISTATE ACETATE; HUMAN B-LYMPHOCYTES; FACTOR EXPRESSION; INTERSUBJECT VARIABILITY; HUMAN MONOCYTES; MESSENGER-RNA; WHOLE-BLOOD; FACTOR-VII; THROMBOSIS AB Background: To date, there is no unequivocal opinion on whether human eosinophils express tissue factor (TF). Therefore, we studied the expression of TF protein and activity in resting or stimulated immunologically purified human eosinophils. Methods and results: By use of immunologic isolation, we achieved over 96% purity of eosinophil preparations, and contamination by CD14-positive cells was below 0.3%. Flow cytometric [fluorescence-activated cell sorting (FACS)] analysis of eosinophils revealed no surface expression of TF antigen in resting or stimulated eosinophils. Immunoblotting of eosinophil lysates did not show any TF protein under resting or stimulated conditions. The lysates of resting or stimulated eosinophils contained no detectable levels of TF procoagulant activity. In contrast, monocytes, stimulated in plasma or medium, possessed readily detectable TF levels on the cell surface and in cell lysates as detected by FACS and immunoblotting. This was active TF antigen, as confirmed by TF activity assay (19.2 +/- 4.2 and 28.6 +/- 3.1 mU per 10(6) cells, stimulated in medium or plasma, respectively). We found no detectable TF mRNA levels in resting or stimulated eosinophils by real-time polymerase chain reaction (PCR), whereas in monocytes TF mRNA levels were significantly increased after stimulation. Conclusions: Our data indicate that there is no evidence for TF expression in high-purity preparations of immunologically isolated eosinophils. C1 [Sovershaev, M. A.] Univ Hosp N Norway, Dept Med, Tromso, Norway. [Lind, K. F.; Jorgensen, T. O.; Osterud, B.; Egorina, E. M.] Univ Tromso, MabCent SFI, Tromso, Norway. [Lind, K. F.; Osterud, B.; Egorina, E. M.] Univ Tromso, Inst Med Biol, Dept Biochem, Tromso, Norway. [Hansen, J. -B.] Univ Tromso, Inst Clin Med, Ctr Atherothrombot Res, Tromso, Norway. RP Egorina, EM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,CLN309, Boston, MA 02114 USA. EM eegorina@partners.org NR 38 TC 19 Z9 19 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD OCT PY 2008 VL 6 IS 10 BP 1742 EP 1749 DI 10.1111/j.1538-7836.2008.03105.x PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 350OK UT WOS:000259361900021 PM 18665928 ER PT J AU Olenchock, B Wiviott, S Murphy, S Cannon, C Rifai, N Braunwald, E Morrow, D AF Olenchock, Benjamin A. Wiviott, Stephen D. Murphy, Sabina A. Cannon, Christopher P. Rifai, Nader Braunwald, Eugene Morrow, David A. TI Lack of association between soluble CD40L and risk in a large cohort of patients with acute coronary syndrome in OPUS TIMI-16 SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Soluble CD40L; Acute coronary syndromes; OPUS; TIMI-16; Biomarkers ID ENDOTHELIAL-CELLS; LIGAND; ATHEROSCLEROSIS; PLASMA; BIOMARKERS; ISCHEMIA AB Background Previous studies have suggested that elevated soluble CD40 ligand (sCD40L) levels predict adverse cardiovascular outcomes in patients with acute coronary syndromes (ACS). Recently, questions have been raised regarding the influence of pre-analytical and analytical conditions on measurement of sCD40L, and additional studies have had conflicting findings regarding the prognostic value of this marker. Methods and Results We measured levels of sCD40L in citrated plasma using an analytically validated automated immunoassay (Roche Diagnostics) in a large cohort of ACS patients (n = 2403) from the placebo arm of the OPUS TIMI-16 trial. No association was observed between elevated sCD40L levels and risk of death or myocardial infarction (MI) (Quartile 1, 8.0%; Quartile 2, 11.7%; Quartile 3, 8.2%; Quartile 4, 6.8%; P = 0.54) or risk of death, MI or heart failure at 10 months (Quartile 1, 9.9%; Quartile 2, 14.2%; Quartile 3, 10.9%; Quartile 4, 8.3%; P = 0.55). A comparison of plasma vs. serum measurements of sCD40L was performed on samples from a nested case-control analysis (n = 42) from within this cohort. Median sCD40L levels did not differ between cases and controls using plasma (0.23 ng/ml vs. 0.27 ng/ml, respectively; P = 0.82) or serum samples (0.64 vs. 0.77, respectively; P = 0.85). Serum samples consistently yielded elevated sCD40L measurements compared to plasma samples (median value 0.72 ng/ml vs. 0.25 ng/ml, respectively, P < 0.001). Conclusions The absence of an association between sCD40L and cardiovascular outcomes in a large cohort of patients with ACS raises concern regarding the reproducibility of clinical results with this novel biomarker. Despite a plausibly important role in the pathobiology of atherothrombosis, pre-analytic sources of variability may limit the practical clinical application of sCD40L. C1 [Olenchock, Benjamin A.; Wiviott, Stephen D.; Murphy, Sabina A.; Cannon, Christopher P.; Braunwald, Eugene; Morrow, David A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,TIMI Study Grp, Boston, MA 02115 USA. [Olenchock, Benjamin A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Rifai, Nader] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Olenchock, B (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM bolenchock@partners.org FU Searle FX The TIMI study group has received grant support from Searle for the performance of the OPUS TIMI-16 study. Roche provided reagents and grant support for analysis of sCD40L. NR 23 TC 20 Z9 22 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD OCT PY 2008 VL 26 IS 2 BP 79 EP 84 DI 10.1007/s11239-007-0156-z PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 368JX UT WOS:000260618500001 PM 17917707 ER PT J AU Pride, Y Buros, J Lord, E Southard, M Harrigan, C Ciaglo, L Sabatine, M Cannon, C Gibson, C AF Pride, Yuri B. Buros, Jacqueline L. Lord, Erin Southard, Matthew C. Harrigan, Caitlin J. Ciaglo, Lauren N. Sabatine, Marc S. Cannon, Christopher P. Gibson, C. Michael CA TIMI Study Grp TI Angiographic perfusion score in patients treated with PCI at late angiography following fibrinolytic administration for ST-segment elevation myocardial infarction is associated with morbidity and mortality at 30 days SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE ST-segment elevation myocardial infarction; TIMI Flow Grade; TIMI Myocardial Perfusion Grade; Angiographic Perfusion Score ID PERCUTANEOUS CORONARY INTERVENTION; TIMI FRAME COUNT; RESCUE ANGIOPLASTY; CLINICAL-OUTCOMES; ELECTROCARDIOGRAPHIC EVIDENCE; REPERFUSION THERAPY; THROMBOLYSIS; ARTERY; REVASCULARIZATION; TISSUE AB Among patients with ST-segment elevation myocardial infarction (STEMI), evidence of restoration of both normal epicardial arterial flow and myocardial perfusion early after the administration of fibrinolytic agents has been associated with improved clinical outcomes. In STEMI patients treated with fibrinolytic therapy and scheduled for angiography later during hospital admission, however, the association of later indices of flow and perfusion with clinical outcomes has not been assessed. Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction (CLARITY-TIMI) 28 enrolled 3,491 STEMI patients treated with fibrinolytic therapy. Angiography was scheduled 48-192 h (median 84) after randomization. The Angiographic Perfusion Score (APS) (the sum of the TIMI Flow Grade and Myocardial Perfusion Grade before and after percutaneous coronary intervention (PCI), range of 0-12) was assessed in the 1,460 patients treated with PCI at late angiography, and its association with morbidity and mortality at 30 days was examined. Full perfusion, defined as an APS of 10-12, was associated with the lowest mortality (0.8%), while partial perfusion (APS 4-9) (2.3%) and failed perfusion (APS 0-3) (18.0%) were associated with a higher incidence of mortality at 30 days (P < 0.001 for full perfusion vs. partial perfusion, P < 0.0001 for overall trend). In addition, full perfusion was associated with a lower incidence of recurrent myocardial infarction (MI), a composite of death and MI, recurrent myocardial ischemia, ventricular tachyarrhythmia, congestive heart failure and shock (P < 0.05 for all trends). Among STEMI patients treated with late PCI following fibrinolytic therapy, higher APS is associated with reduced morbidity and mortality. C1 [Buros, Jacqueline L.; Lord, Erin; Southard, Matthew C.; Harrigan, Caitlin J.; Ciaglo, Lauren N.; Gibson, C. Michael] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, TIMI Study Grp, Boston, MA 02115 USA. [Pride, Yuri B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. [Sabatine, Marc S.; Cannon, Christopher P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. RP Gibson, C (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@perfuse.org OI Buros, Jacqueline/0000-0001-9588-4889 FU Sanofi-Aventis, Paris, France; Bristol-Myers Squibb, Princeton, NJ FX This article is supported by a grant from Sanofi-Aventis, Paris, France and Bristol-Myers Squibb, Princeton, NJ. NR 24 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD OCT PY 2008 VL 26 IS 2 BP 106 EP 112 DI 10.1007/s11239-007-0075-z PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 368JX UT WOS:000260618500006 PM 17624497 ER PT J AU Reisner, AT Chen, LY McKenna, TM Reifman, J AF Reisner, Andrew T. Chen, Liangyou McKenna, Thomas M. Reifman, Jaques TI Automatically-Computed Prehospital Severity Scores are Equivalent to Scores Based on Medic Documentation SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Remote triage; Monitoring; Trauma score; Vital signs; Signal quality ID CHARACTERISTIC ROC CURVES; TRAUMA SCORE; TRIAGE; SYSTEM; ALGORITHMS; MORTALITY; TRANSPORT; SCALE AB Background: Prehospital severity scores can be used in routine prehospital care, mass casualty care, and military triage. If computers could reliably calculate clinical scores, new clinical and research methodologies would be possible. One obstacle is that vital signs measured automatically can be unreliable. We hypothesized that Signal Quality Indices (SQI's), computer algorithms that differentiate between reliable and unreliable monitored physiologic data, could improve the predictive power of computer-calculated scores. Methods: In a retrospective analysis of trauma casualties transported by air ambulance, we computed the Triage Revised Trauma Score (RTS) from archived travel monitor data. We compared the areas-under-the-curve (AUC's) of receiver operating characteristic curves for prediction of mortality and red blood cell transfusion for 187 subjects with comparable quantities of good-quality and poor-quality data. Results. Vital signs deemed reliable by SQI's led to significantly more discriminatory severity scores than vital signs deemed unreliable. We also compared automatically-computed RTS (using the SQI's) versus RTS computed from vital signs documented by medics. For the subjects in whom the SQI algorithms identified 15 consecutive seconds of reliable vital signs data (n = 350), the automatically-computed scores' AUC's were the same as the medic-based scores' AUC's. Using the Prehospital Index in place of RTS led to very similar results, corroborating our findings. Conclusions: SQI algorithms improve automatically-computed severity scores, and automatically-computed scores using SQI's are equivalent to medic-based scores. C1 [Reifman, Jaques] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Reisner, Andrew T.; Chen, Liangyou; McKenna, Thomas M.; Reifman, Jaques] USA, Med Res & Mat Command, TATRC, Ft Detrick, MD USA. RP Reisner, AT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM areisner@partners.org FU Combat Casualty Care Directorate of the U.S. Army Medical Research and Materiel Command, Fort Detrick, MD FX Supported by the Combat Casualty Care Directorate of the U.S. Army Medical Research and Materiel Command, Fort Detrick, MD. NR 40 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD OCT PY 2008 VL 65 IS 4 BP 915 EP 923 DI 10.1097/TA.0b013e31815eb142 PG 9 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 361JS UT WOS:000260124500035 PM 18849811 ER PT J AU Sonis, J Palmieri, PA Lauterbach, D King, LA King, DW AF Sonis, Jeffrey Palmieri, Patrick A. Lauterbach, Dean King, Lynda A. King, Daniel W. TI Innovations in Trauma Research Methods, 2007 SO JOURNAL OF TRAUMATIC STRESS LA English DT Editorial Material C1 [Sonis, Jeffrey] Univ N Carolina, Dept Social Med, Sch Med, Chapel Hill, NC 27599 USA. [Sonis, Jeffrey] Univ N Carolina, Dept Family Med, Chapel Hill, NC 27599 USA. [Palmieri, Patrick A.] Kent State Univ, Dept Psychiat, Kent, OH 44242 USA. [Palmieri, Patrick A.] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. [Lauterbach, Dean] Eastern Michigan Univ, Dept Psychol, Ypsilanti, MI 48197 USA. [King, Lynda A.; King, Daniel W.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [King, Lynda A.; King, Daniel W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [King, Lynda A.; King, Daniel W.] VA Boston Healthcare Syst, Boston, MA USA. RP Sonis, J (reprint author), Univ N Carolina, Dept Social Med, Sch Med, Room 345A MacNider,CB 7240, Chapel Hill, NC 27599 USA. EM jsonis@med.unc.edu FU NIMH NIH HHS [5 R13 MH068798-04] NR 5 TC 1 Z9 1 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2008 VL 21 IS 5 BP 431 EP 432 DI 10.1002/jts.20358 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 372MD UT WOS:000260904800001 PM 18956448 ER PT J AU Gagnon, DR Doron-LaMarca, S Bell, M O'Farrell, TJ Taft, CT AF Gagnon, David R. Doron-LaMarca, Susan Bell, Margret O'Farrell, Timothy J. Taft, Casey T. TI Poisson Regression for Modeling Count and Frequency Outcomes in Trauma Research SO JOURNAL OF TRAUMATIC STRESS LA English DT Article AB The authors describe bow the Poisson regression method for analyzing count or frequency outcome variables can be applied in trauma studies. The outcome of interest in trauma research may represent a count of the number of incidents of behavior occurring in a given time interval, such as acts of physical aggression or substance abuse. Traditional regression approacbes assume a normally distributed outcome variable with equal variances over the range of predictor variables, and may not be optimal for modeling count outcomes. An application Poisson regression is presented using data from a study of intimate partner agression among male patients in an alcohol treatment program and their female partners. Results of Poisson regression and linear regression models are compared. C1 [Gagnon, David R.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Doron-LaMarca, Susan; Taft, Casey T.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Doron-LaMarca, Susan; Taft, Casey T.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. [Bell, Margret] VA Boston Healthcare Syst, Mil Sexual Trauma Support Team, Dept Vet Affairs, Off Mental Hlth Serv, Boston, MA USA. [Bell, Margret] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [O'Farrell, Timothy J.] Harvard Univ, Sch Med, Families & Addict Program, Dept Psychiat, Brockton, MA 02401 USA. [O'Farrell, Timothy J.] VA Boston Healthcare Syst, Brockton, MA USA. [Gagnon, David R.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Gagnon, DR (reprint author), VA Boston Healthcare Syst 151 MAV, Massachusetts Vet Epidemiol & Res Informat Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM gagnon@bu.edu OI Gagnon, David/0000-0002-6367-3179 FU NIAAA NIH HHS [R01AA10796]; NIMH NIH HHS [R03MH77907] NR 17 TC 22 Z9 22 U1 2 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2008 VL 21 IS 5 BP 448 EP 454 DI 10.1002/jts.20359 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 372MD UT WOS:000260904800004 PM 18956443 ER PT J AU Thompson, IM Ankerst, DP Etzioni, R Wang, T AF Thompson, Ian M. Ankerst, Donna P. Etzioni, Ruth Wang, Thomas TI It's time to abandon an upper limit of normal for prostate specific antigen: Assessing the risk of prostate cancer SO JOURNAL OF UROLOGY LA English DT Editorial Material ID EXTERNAL VALIDATION; PREVENTION TRIAL; SERUM; MEN; LEVEL; CALCULATOR; PREVALENCE; BIOPSIES; NG/ML C1 [Thompson, Ian M.; Ankerst, Donna P.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Etzioni, Ruth] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Wang, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Thompson, IM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 28 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2008 VL 180 IS 4 BP 1219 EP 1222 DI 10.1016/j.juro.2008.07.089 PN 1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 350VS UT WOS:000259382300023 PM 18707707 ER PT J AU Crawford, RS Pedraza, JD Chung, TK Corey, M Conrad, MF Cambria, RP AF Crawford, Robert S. Pedraza, Juan D. Chung, Thomas K. Corey, Michael Conrad, Mark F. Cambria, Richard P. TI Functional outcome after thoracoabdominal aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Eastern-Vascular-Society CY SEP 28-30, 2006 CL Washington, DC SP Eastern Vasc Soc ID QUALITY-OF-LIFE; ARTERY-BYPASS SURGERY; THORACIC AORTIC-ANEURYSMS; SURGICAL REPAIR; HYBRID APPROACH; DISEASE; EXPERIENCE; OPERATIONS; SELECTION; GENDER AB Objectives. Previous reports have documented perioperative outcomes and major complications (renal failure, spinal cord ischemia, death) after repair of aneurysms of the thoracoabdominal aorta (TAA). This study documented long-term functional outcomes after open TAA repair. Methods: The Medical Outcomes Study Short-Form 36-Item Survey (SF-36) was administered to 134 survivors (83 men, 51 women; mean age, 69.5 years) of TAA repair at a mean follow-up from surgery of 60 +/- 38.7 months. Raw scores were compared against cohorts adjusted for age and comorbidity (cardiovascular disease). Assessed was the influence of preoperative and intraoperative factors, as well as postoperative complications on long-term quality of life (QOL). Results: Raw scores for the eight SF-36 domains and the composite physical and mental component scores were lower (P < .01) in the TAA cohort compared with an age-adjusted reference population. Female gender and age >75 years decreased the physical functioning (P = .02) and role physical (P = .04) domains compared with male gender and patients <65 years old. Previously recognized systemic vascular disease lowered QOL in three SF-36 domains: general health (P = .013), social functioning (P = .003), and role emotional (P = .003); systemic vascular disease also showed a strong trend toward reduction in physical functioning (P = .09) compared with patients without systemic vascular disease. Neither TAA extent (I to W) nor elective vs urgent/emergency operation influenced long-term QOL in our cohort. Patients with postoperative paraplegia, cerebrovascular accident/cardiac event, and those requiring reoperation showed lower scores in the physical functioning (P = .036), general health (P = .02), and Mental Health (P = .04) domains. Increased length of stay negatively impacted long-term QOL. The TAA cohort and the cardiovascular disease cohort had similar SF-36 scores for four domains (general health, bodily pain, vitality, and social functioning) and physical component scores. The cardiovascular disease group had higher scores in the physical functioning, role physical, role emotional, and mental health domains, and in mental component scores (P < .01). Conclusion: Permanent loss of functional capacity, measured at a mean of 5 years postoperatively, occurs rarely in survivors of TAA repair. Further studies are needed to define the role of hybrid or endovascular strategies, including their impact on long-term functional outcome compared with open TAA repair. C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Gen Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cambria, RP (reprint author), 15 Parkman St, Boston, MA 02114 USA. EM rcambria@partners.org OI Chung, Thomas/0000-0001-6148-1184 NR 33 TC 18 Z9 18 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2008 VL 48 IS 4 BP 828 EP 835 DI 10.1016/j.jvs.2008.05.018 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 353NR UT WOS:000259575200008 PM 18657946 ER PT J AU Kang, JL Patel, VI Conrad, MF LaMuraglia, GM Chung, TK Cambria, RP AF Kang, Jeanwan L. Patel, Virendra I. Conrad, Mark F. LaMuraglia, Glenn M. Chung, Thomas K. Cambria, Richard P. TI Common femoral artery occlusive disease: Contemporary results following surgical endarterectomy SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Society-for-Clinical-Vascular-Surgery CY MAR 05-08, 2008 CL Las Vegas, NV SP Soc Clin Vasc Surg ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; CRITICAL LIMB ISCHEMIA; BIFURCATION; MANAGEMENT; STENT; REVASCULARIZATION AB Objective: Proliferation of endovascular techniques with perceived reduction in treatment morbidity repetitively question the precept that surgical endarterectomv is the preferred treatment for occlusive disease of the common femoral artery (CFA). This study details a contemporary experience with common femoral endarterectomy (CFE) with and without concomitantly performed endovascular therapies. Methods. Technical, hemodynamic, and clinical success of CFE performed between 2002 and 2005 were determined according to the Society of Vascular Surgery reporting standards. Primary and assisted patencies of the CFA segment, freedom front reintervention in the ipsilateral limb, and survival were assessed using Kaplan-Meier life-table analysis. Multivariate analysis was performed to evaluate factors associated with patency and survival. Results. CFE was performed on 65 limbs in 58 patients (mean age 71 +/- 10; male 77%; diabetes 28%; creatinine >= 1.5 mg/dL 19%). Forty-four cases (68%) were performed for claudication, and 21 cases (32%) for critical limb ischemia. Thirty-seven cases (57%) were performed as a hybrid procedure wherein concomitant endovascular interventions were performed. Twenty iliac (TASC II A-30%; B-35%; C-20%; D-15%) and 25 femoropopliteal (TASC II A-24%; B-60%; C-12%; D-4%) lesions were treated. Technical success was achieved in 100% of the cases. Hemodynamic success was achieved in 95% of the cases with mean postoperative increase in ankle-brachial index (ABI) of 0.24 +/- 0.24. All but one patient (98.5%) had improvement in symptoms and/or ABI. Average hospital stay was 3.2 days (range 1-12 days). There were 3 (5%) major complications requiring reintervention (early failure secondary to untreated inflow lesion, hematoma, and wound infection), six (9%) minor complications which were treated conservatively (five wound infections, one lymph leak), and no perioperative mortality. With a mean follow-up period of 27 months (range 1-58 months), 1- and 5-year primary patencies were 93% and 91%, respectively. Assisted patency was 100% at both time points. There was no difference in patencies between CFE performed alone or as a hybrid procedure. Multivariate analysis showed congestive heart failure (CHF) as the only predictor of primary failure (odds ratio [OR] 18.5 [2.6-142.9]; P = .004). Freedom from reintervention in the ipsilateral limb was 82% at 1 year and 78% at 5 years, with CHF again as the only predictor of reintervention (OR 5.3 [1.4-19.6 1; P = .012). Survival was 89% at 1 year and 70% at 5 years. There were no amputations. Conclusions: These data suggest CFE should remain the standard of care for occlusive disease of the CFA. Its safety and efficacy establish a standard for comparison with emerging endovascular therapies. C1 [Cambria, Richard P.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Dept Surg, 15 Parkman St,WAC-04-410, Boston, MA 02114 USA. EM sguatreau1@partners.org OI Chung, Thomas/0000-0001-6148-1184 NR 23 TC 73 Z9 79 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2008 VL 48 IS 4 BP 872 EP 877 DI 10.1016/j.jvs.2008.05.025 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 353NR UT WOS:000259575200015 PM 18639427 ER PT J AU Alter, G Rihn, S Streeck, H Teigen, N Piechocka-Trocha, A Moss, K Cohen, K Meier, A Pereyra, F Walker, B Altfeld, M AF Alter, Galit Rihn, Suzannah Streeck, Hendrik Teigen, Nickolas Piechocka-Trocha, Alicja Moss, Kristin Cohen, Kristen Meier, Angela Pereyra, Florencia Walker, Bruce Altfeld, Marcus TI Ligand-independent exhaustion of killer immunoglobulin-like receptor-positive CD8(+) T cells in human immunodeficiency virus type 1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; CHRONIC VIRAL-INFECTION; ACUTE HIV-1 INFECTION; IG-LIKE RECEPTORS; HIV-1-INFECTED INDIVIDUALS; DISEASE PROGRESSION; EFFECTOR FUNCTIONS; IMMUNE-RESPONSES; EXPRESSION; LYMPHOCYTES AB Virus-specific CD8(+) T cells play a central role in the control of viral infections, including human immunodeficiency virus type 1 (HIV-1) infection. However, despite the presence of strong and broad HIV-specific CD8(+) T-cell responses in chronic HIV-1 infection, these cells progressively lose critical effector functions and fail to clear the infection. Mounting evidence suggests that the upregulation of several inhibitory regulatory receptors on the surface of CD8(+) T cells during HIV-1 infection may contribute directly to the impairment of T-cell function. Here, we investigated the role of killer immunoglobulin receptors (KIR), which are expressed on NK cells and on CD8(+) T cells, in regulating CD8(+) T-cell function in HIV-1 infection. KIR expression was progressively upregulated on CD8(+) T cells during HIV-1 infection and correlated with the level of viral replication. Expression of KIR was associated with a profound inhibition of cytokine secretion, degranulation, proliferation, and activation by CD8(+) T cells following stimulation with T-cell receptor (TCR)-dependent stimuli. In contrast, KIR+ CD8(+) T cells responded potently to TCR-independent stimulation, demonstrating that these cells are functionally competent. KIR-associated suppression of CD8(+) T-cell function was independent of ligand engagement, suggesting that these regulatory receptors may constitutively repress TCR activation. This ligand-independent repression of TCR activation of KIR+ CD8(+) T cells may represent a significant barrier to therapeutic interventions aimed at improving the quality of the HIV-specific CD8(+) T-cell response in infected individuals. C1 [Alter, Galit; Rihn, Suzannah; Streeck, Hendrik; Teigen, Nickolas; Piechocka-Trocha, Alicja; Moss, Kristin; Cohen, Kristen; Meier, Angela; Pereyra, Florencia; Walker, Bruce; Altfeld, Marcus] Harvard Univ, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Alter, G (reprint author), Harvard Univ, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Sch Med, 149 13th St, Boston, MA 02129 USA. EM galter@partners.org FU NIH [K99AI072973]; Harvard University Center for AIDS Research (HU CFAR) FX These studies were supported by NIH grant K99AI072973 and the Harvard University Center for AIDS Research (HU CFAR). NR 38 TC 18 Z9 20 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2008 VL 82 IS 19 BP 9668 EP 9677 DI 10.1128/JVI.00341-08 PG 10 WC Virology SC Virology GA 349DT UT WOS:000259259700035 PM 18579582 ER PT J AU Radziewicz, H Ibegbu, CC Hon, HM Osborn, MK Obideen, K Wehbi, M Freeman, GJ Lennox, JL Workowski, KA Hanson, HL Grakoui, A AF Radziewicz, Henry Ibegbu, Chris C. Hon, Huiming Osborn, Melissa K. Obideen, Kamil Wehbi, Mohammad Freeman, Gordon J. Lennox, Jeffrey L. Workowski, Kimberly A. Hanson, Holly L. Grakoui, Arash TI Impaired Hepatitis C Virus (HCV)-Specific Effector CD8(+) T Cells Undergo Massive Apoptosis in the Peripheral Blood during Acute HCV Infection and in the Liver during the Chronic Phase of Infection SO JOURNAL OF VIROLOGY LA English DT Article ID PD-1 EXPRESSION; IMMUNE-RESPONSE; GRANZYME-A; SELECTIVE EXPRESSION; INTERFERON-GAMMA; VIRAL-INFECTION; IN-VIVO; LYMPHOCYTES; DEATH; RECEPTOR AB A majority of patients infected with hepatitis C virus (HCV) do not sustain an effective T-cell response, and viremia persists. The mechanism leading to failure of the HCV-specific CD8(+) T-cell response in patients developing chronic infection is unclear. We investigated apoptosis susceptibility of HCV-specific CD8(+) T cells during the acute and chronic stages of infection. Although HCV-specific CD8(+) T cells in the blood during the acute phase of infection and in the liver during the chronic phase were highly activated and expressed an effector phenotype, the majority was undergoing apoptosis. In contrast, peripheral blood HCV-specific CD8(+) T cells during the chronic phase expressed a resting memory phenotype. Apoptosis susceptibility of HCV-specific CD8(+) T cells was associated with very high levels of programmed death-1 (PD-1) and low CD127 expression and with significant functional T-cell deficits. Further evaluation of the "death phase" of HCV-specific CD8(+) T cells during acute HCV infection showed that the majority of cells were dying by a process of cytokine withdrawal, mediated by activated caspase 9. Contraction during the acute phase occurred rapidly via this process despite the persistence of the virus. Remarkably, in the chronic phase of HCV infection, at the site of infection in the liver, a substantial frequency of caspase 9-mediated T-cell death was also present. This study highlights the importance of cytokine deprivation-mediated apoptosis with consequent down-modulation of the immune response to HCV during acute and chronic infections. C1 [Radziewicz, Henry; Ibegbu, Chris C.; Hanson, Holly L.; Grakoui, Arash] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Radziewicz, Henry; Ibegbu, Chris C.; Hanson, Holly L.; Grakoui, Arash] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Radziewicz, Henry; Hon, Huiming; Osborn, Melissa K.; Obideen, Kamil; Wehbi, Mohammad; Lennox, Jeffrey L.; Workowski, Kimberly A.; Grakoui, Arash] Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Grakoui, A (reprint author), Emory Univ, Sch Med, 954 Gatewood Rd NE, Atlanta, GA 30329 USA. EM arash.grakoui@emory.edu RI Lennox, Jeffrey/D-1654-2014 OI Lennox, Jeffrey/0000-0002-2064-5565 FU Grand Challenges in Global Health Initiative; EVC/CFAR Flow Cytometry Core [P30 AI050409]; Cancer Research Institute Investigator Award; Woodruff Health Sciences Fund; Yerkes Research Center Base [RR-00165]; Public Health Service [K08 AI072191, AI56299, AI070101] FX We thank Dimitri Fillos for excellent technical assistance and Francie Lasseter, Beverly Weaver, and Ellen Katz for patient cohort coordination. We thank Enrique Martinez for his contribution to this research.; We acknowledge the support from the Grand Challenges in Global Health Initiative (G. F.), EVC/CFAR Flow Cytometry Core P30 AI050409, Cancer Research Institute Investigator Award (A. G.), Woodruff Health Sciences Fund (A. G.), the Yerkes Research Center Base Grant RR-00165, and the Public Health Service (K08 AI072191 to H. R., AI56299 to G. F., and AI070101 to A. G.). NR 62 TC 51 Z9 53 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2008 VL 82 IS 20 BP 9808 EP 9822 DI 10.1128/JVI.01075-08 PG 15 WC Virology SC Virology GA 361EA UT WOS:000260109100001 PM 18667503 ER PT J AU Krum, SA Brown, M AF Krum, Susan A. Brown, Myles TI Cell-Type-Specific Regulation of Transcription by Estrogen SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Krum, Susan A.] Univ Calif Los Angeles, Dept Orthoped Surg, Los Angeles, CA USA. [Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. RI krum, susan/D-7282-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2008 VL 17 IS 8 BP 1238 EP 1239 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 378OE UT WOS:000261331200035 ER PT J AU Torres-Arzayus, MI Zhao, J Brown, M AF Torres-Arzayus, Maria I. Zhao, Jin Brown, Myles TI Cyclin D1 Can Act as a Positive or Negative Effector in AIB1-Mediated Tumorigenesis SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Torres-Arzayus, Maria I.; Zhao, Jin; Brown, Myles] Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2008 VL 17 IS 8 BP 1240 EP 1240 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 378OE UT WOS:000261331200041 ER PT J AU Schauer, I Bergman, B Snell-Bergeon, J Maahs, DM Eckel, RH Rewers, M AF Schauer, Irene Bergman, Bryan Snell-Bergeon, Janet Maahs, David M. Eckel, Robert H. Rewers, Marian TI Insulin Resistance in Type 1 Diabetes Correlates With Coronary Artery Calcification SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Schauer, Irene; Bergman, Bryan; Eckel, Robert H.] Univ Colorado, Dept Med, Div Endocrinol, Denver, CO USA. [Schauer, Irene] Denver VA Med Ctr, Dept Med, Div Endocrinol, Denver, CO USA. [Snell-Bergeon, Janet; Maahs, David M.; Rewers, Marian] Univ Colorado, Dept Pediat, Barbara Davis Ctr Childhood Diabet, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2008 VL 17 IS 8 BP 1242 EP 1242 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 378OE UT WOS:000261331200047 ER PT J AU Larauche, MH Yuan, PQ Wang, L Mulugeta, M Tache, Y AF Larauche, Muriel H. Yuan, Pu-Qing Wang, Lixin Mulugeta, Million Tache, Yvette. TI Sex-Related Differences of Colonic Response to Stress: Role of Colonic Corticotropin Releasing Factor SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Larauche, Muriel H.] Univ Calif Los Angeles, Dept Med, Specialized Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90024 USA. Div Digest Dis, Los Angeles, CA USA. VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2008 VL 17 IS 8 BP 1252 EP 1253 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 378OE UT WOS:000261331200076 ER PT J AU Hutt, E Radcliff, TA Liebrecht, D Fish, R McNulty, M Kramer, AM AF Hutt, Evelyn Radcliff, Tiffany A. Liebrecht, Debra Fish, Ron McNulty, Monica Kramer, Andrew M. TI Associations Among Nurse and Certified Nursing Assistant Hours per Resident per Day and Adherence to Guidelines for Treating Nursing Home-Acquired Pneumonia SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Nursing homes; Pneumonia; Nurse staffing ID MINIMUM DATA SET; HOSPITALIZATION; OUTCOMES; QUALITY; CARE AB Background. Nursing home (NH)-acquired pneumonia (NHAP) causes excessive mortality, hospitalization, and functional decline, partly because many NH residents do not receive appropriate care. Care structures like nurse/resident staffing ratios can impede or abet quality care. This study examines the relationship between nurse/resident staffing ratios, turnover, and adherence to evidence-based guidelines for treating NHAP. Methods. A prospective, chart-review study was conducted among residents of 16 NHs in three states with >= 2 signs and symptoms of NHAP during the 2004-2005 influenza season. NH medical records were reviewed concurrently for functional status, comorbidity, NHAP severity, and guideline adherence. Ratio of licensed nurse and Certified Nursing Assistant (CNA) hours per resident per day (hrpd) and ratio of newly hired nursing staff/year to current nursing staff were provided by Directors of Nursing. Associations among guideline adherence, nurse and CNA hrpd, and turnover were assessed using multiple regression to adjust for case mix, facility characteristics, and clustering of residents in facilities. Results. Mid (1.7-2.0) and high (> 2.0) CNA hrpd were significantly associated with better pneumococcal and influenza vaccination rates. More than 1.2 licensed nurse hrpd was significantly associated with appropriate hospitalization (odds ratio [OR] 12.4: 95% confidence interval [CI], 3.5-43.8) and guideline-recommended antibiotics (OR 3.8: 95% CI, 1.7-8.7). A > 70% turnover was inversely related to timely physician notification (OR 0.4: 95% CI. 0.2-0.7) and appropriate hospitalization (OR 0.09: 95% CI, 0.05-0.26). Conclusions. NHAP treatment guideline adherence is associated with rtursc and CNA hr-Ixl and stability. An NI-I's ability to implement evidence-based care may depend on adeqtnnc staffing ratios and stability. C1 [Hutt, Evelyn] Denver VA Med Ctr, Colorado REAP Improve Care Coordinat CRICC, Denver, CO 80220 USA. [Hutt, Evelyn; Radcliff, Tiffany A.; Liebrecht, Debra; Fish, Ron; McNulty, Monica; Kramer, Andrew M.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Hutt, E (reprint author), Denver VA Med Ctr, Colorado REAP Improve Care Coordinat CRICC, 151,1055 Clermont St, Denver, CO 80220 USA. EM erelyn.hutt@uchsc.edu FU National Institutes of Health to the University of Colorado Health Sciences Center [AHRQ 5 R01-HS013618-04] FX This work was supported by AHRQ 5 R01-HS013618-04 from the National Institutes of Health to the University of Colorado Health Sciences Center (Principal Investigator Evelyn Hutt). NR 28 TC 10 Z9 10 U1 0 U2 2 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD OCT PY 2008 VL 63 IS 10 BP 1105 EP 1111 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 366LS UT WOS:000260483600012 PM 18948562 ER PT J AU Hadlock, T Kowaleski, J Lo, D Bermejo, R Zeigler, HP Mackinnon, S Heaton, JT AF Hadlock, Tessa Kowaleski, Jeffrey Lo, David Bermejo, Roberto Zeigler, H. Philip Mackinnon, Susan Heaton, James T. TI Functional Assessments of the Rodent Facial Nerve: A Synkinesis Model SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Peripheral-Nerve CY JAN 09, 2008 CL Beverly Hills, CA SP Amer Soc Peripheral Nerve DE Rodent facial nerve; synkinesis; whisking; kinematics ID ORBICULARIS OCULI MUSCLE; WHISKER MOVEMENTS; MOTOR NUCLEUS; ADULT-RATS; IN-VIVO; REGENERATION; RECOVERY; REINNERVATION; TRANSECTION; ANASTOMOSIS AB Objectives/Hypothesis: Rodent whisker movement has been used as a tool, after facial nerve manipulation, to quantify functional recovery. We have recently established a method to study functional correlates of aberrant regeneration of the facial nerve. Our objective was to establish normative parameters for both spontaneous and induced whisking and blinking behavior in a large group of normal rats. Study Design: Prospective animal study. Methods: Eighty animals underwent quantitative facial movement testing to measure simultaneous vibrissal movement and ocular closure for each side independently. Right and left C-1 whisker positions were continuously recorded for 5-minute sessions, and changes in infrared detection corresponding to eye closure were continuously recorded. Whisking and blinking were elicited by delivery of olfactory stimuli (10 s scented airflows) and corneal air puffs. Whisks were counted and analyzed, and eye closures were counted. Results: Whisking amplitude, velocity, and acceleration were consistent with literature values. Air puff delivery elicited an ipsilateral blink 99% of the time, a contralateral blink 18% of the time, and changes in or initiation of bilateral whisking 70% of the time. Olfactory stimulus delivery prompted a change in whisking behavior 83% of the time, and eye closure 20% of the time. Conclusions: This study establishes normative data for assessing cranial nerve VII-controlled facial movement in four separate facial regions. We demonstrate the capability and tendency of animals to move their orbicularis oculi muscles independently of and simultaneously with their midfacial muscles. This model provides an excellent tool for the study of aberrant regeneration after facial nerve injury in the rodent. C1 [Hadlock, Tessa; Kowaleski, Jeffrey; Lo, David] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. [Bermejo, Roberto; Zeigler, H. Philip] CUNY, CUNY Hunter Coll, Biopsychol Program, New York, NY 10021 USA. [Mackinnon, Susan] Washington Univ, Div Plast & Reconstruct Surg, Dept Surg, St Louis, MO USA. [Heaton, James T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu FU NIDCR NIH HHS [K-08 DE015665-01A2] NR 35 TC 21 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2008 VL 118 IS 10 BP 1744 EP 1749 DI 10.1097/MLG.0b013e31817f5255 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 368ZR UT WOS:000260662800006 PM 18641527 ER PT J AU Fang, TJ Li, HY Gliklich, RE Chen, YH Wang, PC Chuang, HF AF Fang, Tuan-Jen Li, Hsueh-Yu Gliklich, Richard E. Chen, Ya-Hui Wang, Pa-Chun Chuang, Hsiu-Feng TI Quality of Life Measures and Predictors for Adults With Unilateral Vocal Cord Paralysis SO LARYNGOSCOPE LA English DT Article DE Unilateral vocal cord paralysis; health status; quality of life ID VOICE HANDICAP INDEX; DYSPHONIC PATIENTS; FOLD PARALYSIS; OUTCOME SURVEY; MEDIALIZATION; VALIDATION; SURGERY AB Objective/Hypothesis: To investigate the quality of life (QoLF) status of Taiwanese adults with unilateral vocal cord paralysis (UVCP). Study Design: A prospective, QoLF survey in a tertiary referral voice center. Methods: Fifty-five consecutive UVCP patients were evaluated with Medical Outcome Study Short Form-36 (SF-36) Health Survey and the voice outcome survey at entry. Results: UVCP patients have significantly lower scores in all eight SF-36 subscales (P <.05) than do normative Taiwan adult population, particularly in role firrictioning-physical problems, social functioning, and role functioning-emotional problems. Shimmer parameter is a robust and consistent predictor for bodily pain (beta = -20.8), role functioning-emotional problems (beta = -27.9), and social functioning (beta = -20) general health dimensions. Shimmer is also predictive of UVCP-related total voice outcome survey score (beta = -8.6, P <.05). Conclusions: UVCP can seriously compromise phonation, swallowing, and social functions; thus significantly impacting a patient's general health status. Voice physiological function is also a QoLF outcome indicator. C1 [Fang, Tuan-Jen; Chuang, Hsiu-Feng] Chang Gung Mem Hosp, Dept Otolaryngol, Chilung, Taiwan. [Fang, Tuan-Jen; Li, Hsueh-Yu] Chang Gung Univ, Sch Med, Tao Yuan, Taiwan. [Li, Hsueh-Yu] Chang Gung Mem Hosp, Dept Otolaryngol, Taipei, Taiwan. [Gliklich, Richard E.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Gliklich, Richard E.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Chen, Ya-Hui] Cathay Med Res Inst, Taipei, Taiwan. [Wang, Pa-Chun] Cathay Gen Hosp, Dept Otolaryngol, Taipei, Taiwan. [Wang, Pa-Chun] Fu Jen Catholic Univ, Sch Med, Taipei, Taiwan. [Wang, Pa-Chun] China Med Univ, Sch Publ Hlth, Taichung, Taiwan. RP Wang, PC (reprint author), Cathay Gen Hosp, Dept Otolaryngol Head & Neck Surg, 280 Sec,4 Jen Ai Rd, Taipei 106, Taiwan. EM drtony@tpts4.seed.net.tw NR 21 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2008 VL 118 IS 10 BP 1837 EP 1841 DI 10.1097/MLG.0b013e31817e7431 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 368ZR UT WOS:000260662800025 PM 18806475 ER PT J AU Walsh, CJ Heaton, JT Kobler, JB Szabo, TL Zeitels, SM AF Walsh, Conor J. Heaton, James T. Kobler, James B. Szabo, Thomas L. Zeitels, Steven M. TI Imaging of the Calf Vocal Fold With High-Frequency Ultrasound SO LARYNGOSCOPE LA English DT Article DE Glottis; imaging technique; larynx; ultrasound; vocal fold ID IN-VIVO; MICE AB Objectives/Hypothesis: High-frequency ultrasound imaging offers the potential for assisting in the diagnosis and treatment of vocal fold pathology if it allows aspects of vocal fold microstructure to be visualized noninvasively. The objective of this study was to assess the ability of high-frequency ultrasound to image vocal fold anatomy and injected biomaterials. Study Design: The vocal folds of two excised calf larynges were imaged ex vivo and compared with corresponding histological sections. Methods: High-frequency ultrasound imaging was performed under saline submersion using 40 and 50 MHz transducers, and corresponding cryostat cross-sections were stained with H&E, Trichome, and Verhoeffs Van Gieson stains. Results: The epithelial surface, lamina propria, and underlying muscle were easily identified with the high-frequency ultrasound as verified with histological sections representing each imaged region. The arytenoid cartilage vocal process can also be clearly distinguished from the surrounding tissue, as can the full extent of injected biomaterials within the superficial lamina propria. Useful ultrasound resolution was obtained to depths of at least 10 mm within the tissue with the 40 MHz transducer. Conclusions: This preliminary study demonstrates the capability of high-frequency ultrasound to image the layered anatomy of the calf vocal fold and to discern materials injected into the superficial lamina propria, indicating that this technology holds a strong potential for use in phonosurgery. C1 [Heaton, James T.; Kobler, James B.; Zeitels, Steven M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Szabo, Thomas L.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Kobler, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM james.heaton@mgh.harvard.edu NR 19 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2008 VL 118 IS 10 BP 1894 EP 1899 DI 10.1097/MLG.0b013e31817f18ca PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 368ZR UT WOS:000260662800034 PM 18641528 ER PT J AU Breitkreutz, I Raab, MS Vallet, S Hideshima, T Raje, N Mitsiades, C Chauhan, D Okawa, Y Munshi, NC Richardson, PG Anderson, KC AF Breitkreutz, I. Raab, M. S. Vallet, S. Hideshima, T. Raje, N. Mitsiades, C. Chauhan, D. Okawa, Y. Munshi, N. C. Richardson, P. G. Anderson, K. C. TI Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma SO LEUKEMIA LA English DT Article DE multiple myeloma; osteoclastogenesis; bone disease; lenalidomide; bortezomib ID KAPPA-B LIGAND; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; NECROSIS-FACTOR FAMILY; RECEPTOR ACTIVATOR; PLUS DEXAMETHASONE; OSTEOLYTIC LESIONS; TUMOR BURDEN; C-FOS; CELLS; BORTEZOMIB AB Osteolytic bone disease in multiple myeloma (MM) is caused by enhanced osteoclast (OCL) activation and inhibition of osteoblast function. Lenalidomide and bortezomib have shown promising response rates in relapsed and newly diagnosed MM, and bortezomib has recently been reported to inhibit OCLs. We here investigated the effect of lenalidomide on OCL formation and osteoclastogenesis in comparison with bortezomib. Both drugs decreased alpha Vb3-integrin, tartrate-resistant acid phosphatase-positive cells and bone resorption on dentin disks. In addition, both agents decreased receptor activator of nuclear factor-kappa B ligand (RANKL) secretion of bone marrow stromal cells (BMSCs) derived from MM patients. We identified PU.1 and pERK as major targets of lenalidomide, and nuclear factor of activated T cells of bortezomib, resulting in inhibition of osteoclastogenesis. Furthermore, downregulation of cathepsin K, essential for resorption of the bone collagen matrix, was observed. We demonstrated a significant decrease of growth and survival factors including macrophage inflammatory protein-alpha, B-cell activating factor and a proliferation-inducing ligand. Importantly, in serum from MM patients treated with lenalidomide, the essential bone-remodeling factor RANKL, as well as the RANKL/OPG ratio, were significantly reduced, whereas osteoprotegerin (OPG) was increased. We conclude that both agents specifically target key factors in osteoclastogenesis, and could directly affect the MM-OCL-BMSCs activation loop in osteolytic bone disease. C1 [Breitkreutz, I.; Raab, M. S.; Vallet, S.; Hideshima, T.; Raje, N.; Mitsiades, C.; Chauhan, D.; Okawa, Y.; Munshi, N. C.; Richardson, P. G.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr,LeBow Inst Mye, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr,LeBow Inst Mye, 44 Binney St, Boston, MA 02115 USA. EM Iris_Breitkreutz@dfci.harvard.edu; Kenneth_Anderson@dfci.harvard.edu FU Multiple Myeloma Research Foundation; National Foundation of Cancer Research; NIH [CA50947, CA78373, CA10070] FX We thank the patients, nursing staff as well as the clinical research coordinators of the Jerome Lipper Multiple Myeloma Center/Dana-Farber Cancer Institute, for their help in providing serum specimens for this study. This work was supported by the Multiple Myeloma Research Foundation, LeBow Fund to Cure Myeloma (KCA); National Foundation of Cancer Research and NIH grants CA50947, CA78373 and CA10070. NR 41 TC 119 Z9 123 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2008 VL 22 IS 10 BP 1925 EP 1932 DI 10.1038/leu.2008.174 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 359SA UT WOS:000260007200014 PM 18596740 ER PT J AU Stone, ME AF Stone, Martha E. TI The changing face of medicine: Women doctors and the evolution of health care in America SO LIBRARY JOURNAL LA English DT Book Review C1 [Stone, Martha E.] Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU REED BUSINESS INFORMATION PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD OCT 1 PY 2008 VL 133 IS 16 BP 87 EP 87 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 356CM UT WOS:000259756300174 ER PT J AU Sabharwal, S Delgado-Borrego, A Chung, RT AF Sabharwal, Sabina Delgado-Borrego, Aymin Chung, Raymond T. TI Extrahepatic hepatitis C virus after transplantation: Diabetes and renal dysfunction SO LIVER TRANSPLANTATION LA English DT Article ID II MIXED CRYOGLOBULINEMIA; INSULIN-RESISTANCE; LIVER-TRANSPLANTATION; INTERFERON-ALPHA; UNITED-STATES; KIDNEY-TRANSPLANTATION; PEGYLATED INTERFERON; DIALYSIS PATIENTS; INFECTION; GLOMERULONEPHRITIS C1 [Sabharwal, Sabina; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Delgado-Borrego, Aymin] Univ Miami, Dept Pediat, Batchelor Childrens Res Inst, Div Clin Res, Miami, FL 33152 USA. [Delgado-Borrego, Aymin] Univ Miami, Dept Pediat, Batchelor Childrens Res Inst, Div Gastroenterol, Miami, FL 33152 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, 55 Fruit St,GRJ 724, Boston, MA 02114 USA. EM rtchung@partners.org NR 55 TC 9 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD OCT PY 2008 VL 14 IS 10 SU 2 BP S51 EP S57 DI 10.1002/lt.21613 PG 7 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 356TL UT WOS:000259800400008 PM 18825714 ER PT J AU Kim, YR Tejima, E Huang, S Atochin, DN Dai, G Lo, EH Huang, PL Bogdanov, A Rosen, BR AF Kim, Y. R. Tejima, E. Huang, S. Atochin, D. N. Dai, G. Lo, E. H. Huang, P. L. Bogdanov, A., Jr. Rosen, B. R. TI In vivo quantification of transvascular water exchange during the acute phase of permanent stroke SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE water exchange; stroke; blood-brain barrier; mouse ID MIDDLE CEREBRAL-ARTERY; ACUTE ISCHEMIC-STROKE; BLOOD-VOLUME; BRAIN EDEMA; VASCULAR PROTECTION; TUMOR ANGIOGENESIS; CELL-VOLUME; DIFFUSION; PERMEABILITY; TIME AB Mechanisms that underlie early ischemic damages to the blood-brain-barrier (BBB) are not well understood. This study presents a novel magnetic resonance imaging (MRI) technique using a widely available pulse sequence and a long-circulating intravascular contrast agent to quantify water movements across the EBB at early stages of stroke progression. We characterized the integrity of the BBB by measuring the flip angle dependence of the water exchange-affected MRI signal intensity, to generate an efficient quantitative index of vascular permeability (WEI, or water exchange index). We performed in vivo MRI experiments to measure the transvascular WEI immediately after the permanent filament occlusion of the middle cerebral artery of mice (n = 5), in which we monitored changes in blood volume (Vb), apparent diffusion coefficient (ADC), and intra-/extravascular WEI for 4 hours. Statistically significant elevations (P < 0.05) of WEI in the ischemic tissue were observed as early as I hour after ischemic onset. Initial reduction of the apparent blood volume (V(app)) in the infarct cortex was followed by a continuous increase of V(app) over time. Although the measured ADC in the ipsilesional cortex continuously decreased, the abnormally high intra-/extravascular WEI remained constant at a significantly elevated level, indicating apparent BBB injury at this early stage of stroke. C1 [Kim, Y. R.; Tejima, E.; Huang, S.; Dai, G.; Rosen, B. R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging Radiol, Charlestown, MA 02129 USA. [Kim, Y. R.; Tejima, E.; Lo, E. H.] Massachusetts Gen Hosp, Neuroprotect Lab Radiol, Charlestown, MA 02129 USA. [Atochin, D. N.; Huang, P. L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr Cardiol, Charlestown, MA 02129 USA. [Bogdanov, A., Jr.] Univ Massachusetts, Sch Med, Worcester, MA USA. RP Kim, YR (reprint author), Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, 149 13th St,Room2301, Charlestown, MA 02129 USA. EM spmn@nmr.mgh.harvard.edu RI Atochin, Dmitriy/Q-3150-2016 FU NIH-NIBIB [2R01EB002066] FX The authors gratefully acknowledge the financial support front NIH-NIBIB grant 2R01EB002066. NR 23 TC 13 Z9 13 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD OCT PY 2008 VL 60 IS 4 BP 813 EP 821 DI 10.1002/mrm.21708 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 354PJ UT WOS:000259651200008 PM 18816832 ER PT J AU Sun, PZ Benner, T Kumar, A Sorensen, AG AF Sun, Phillip Zhe Benner, Thomas Kumar, Ashok Sorensen, A. Gregory TI Investigation of optimizing and translating pH-sensitive pulsed-chemical exchange saturation transfer (CEST) imaging to a 3T clinical scanner SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE amide proton transfer (APT); chemical exchange saturation transfer (CEST); magnetic resonance imaging (MRI); magnetization transfer (MT); pH ID ACUTE CEREBRAL-ISCHEMIA; MAGNETIZATION-TRANSFER; PROTON-EXCHANGE; QUANTITATIVE DESCRIPTION; RESONANCE; MRI; PENUMBRA; RELAXATION; WATER; TIME AB Chemical exchange saturation transfer (CEST) MRI provides a sensitive detection mechanism that allows characterization of dilute labile protons usually undetectable by conventional MRI. Particularly, amide proton transfer (APT) imaging, a variant of CEST MRI, has been shown capable of detecting ischemic acidosis, and may serve as a surrogate metabolic imaging marker. For preclinical CEST imaging, continuous-wave (CW) radiofrequency (RF) irradiation is often applied so that the steady state CEST contrast can be reached. On clinical scanners, however, specific absorption rate (SAR) limit and hardware preclude the use of CW irradiation, and instead require an irradiation scheme of repetitive RF pulses (pulsed-CEST imaging). In this work, CW- and pulsed-CEST MRI were systematically compared using a tissue-like pH phantom on an imager capable of both CW and pulsed RF irradiation schemes. The results showed that the maximally obtainable pulsed-CEST contrast is approximately 95% of CW-CEST contrast, and their optimal RF irradiation powers are equal. Moreover, the pulsed-CEST sequence was translated to a 3 Testa clinical scanner and detected pH contrast from the labile creatine amine groups (1.9 ppm). Furthermore, pilot endogenous APT imaging of normal human volunteers was demonstrated, warranting future APT MRI of stroke patients to elucidate its diagnostic value. C1 [Sun, Phillip Zhe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. RP Sun, PZ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu FU NIH/NINDS [5R01NS038477-09]; NIH/NCRR [P41RR14075]; American Heart Association/Scientist Development Grant [AHA/SDG 0835384N] FX Grant sponsor: NIH/NINDS; Grant number: 5R01NS038477-09; Grant sponsor: NIH/NCRR; Grant number: P41RR14075; Grant sponsor: American Heart Association/Scientist Development Grant, AHA/SDG 0835384N. NR 39 TC 66 Z9 70 U1 5 U2 22 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD OCT PY 2008 VL 60 IS 4 BP 834 EP 841 DI 10.1002/mrm.21714 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 354PJ UT WOS:000259651200010 PM 18816867 ER PT J AU Moss, J Rosow, CE AF Moss, Jonathan Rosow, Carl E. TI Development of peripheral opioid antagonists: New insights into opioid effects SO MAYO CLINIC PROCEEDINGS LA English DT Article ID INDUCED BOWEL DYSFUNCTION; MAJOR ABDOMINAL-SURGERY; CECAL TRANSIT-TIME; QUATERNARY NARCOTIC-ANTAGONISTS; MORPHINE-INDUCED INHIBITION; PLACEBO-CONTROLLED TRIAL; PHASE-III TRIAL; POSTOPERATIVE ILEUS; DOUBLE-BLIND; INDUCED CONSTIPATION AB The recent approval by the US Food and Drug Administration of 2 medications-methylnaltrexone and alvimopan-introduces a new class of therapeutic entities to clinicians. These peripherally acting mu-opioid receptor antagonists selectively reverse opioid actions mediated by receptors outside the central nervous system, while preserving centrally mediated analgesia. Methylnaltrexone, administered subcutaneously, has been approved in the United States, Europe, and Canada. In the United States, it is indicated for the treatment of opioid-Induced constipation in patients with advanced illness (eg, cancer, AIDS) who are receiving palliative care, when response to laxative therapy has not been sufficient. Alvimopan, an orally administered medication, has been approved in the United States to facilitate recovery of gastrointestinal function after bowel resection and primary anastomosis. Clinical and laboratory studies performed during the development of these drugs have indicated that peripheral receptors mediate other opioid effects, including decreased gastric emptying, nausea and vomiting, pruritus, and urinary retention. Laboratory investigations with these compounds suggest that opioids affect fundamental cellular processes through mechanisms that were previously unknown. These mechanisms include modifications of human immunodeficiency virus penetration, tumor angiogenesis, vascular permeability, and bacterial virulence. C1 [Moss, Jonathan] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Rosow, Carl E.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Moss, J (reprint author), Univ Chicago, Dept Anesthesia & Crit Care, 5841 S Maryland Ave,MC 4028, Chicago, IL 60637 USA. EM jm47@midway.uchicago.edu NR 89 TC 44 Z9 47 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2008 VL 83 IS 10 BP 1116 EP 1130 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 359JS UT WOS:000259983500006 PM 18828971 ER PT J AU Ji, SB Wu, ZJ Hartov, A Roberts, DW Paulsen, KD AF Ji, Songbai Wu, Ziji Hartov, Alex Roberts, David W. Paulsen, Keith D. TI Mutual-information-based image to patient re-registration using intraoperative ultrasound in image-guided neurosurgery SO MEDICAL PHYSICS LA English DT Article DE brain shift; intraoperative ultrasound; image-guided surgery; image registration; mutual information ID FREEHAND 3D ULTRASOUND; MAGNETIC-RESONANCE; BRAIN SHIFT; RIGID REGISTRATION; 3-D ULTRASOUND; ULTRASONOGRAPHY; COMPENSATION; CALIBRATION; SURGERY AB An image-based re-registration scheme has been developed and evaluated that uses fiducial registration as a starting point to maximize the normalized mutual information (nMI) between intraoperative ultrasound (iUS) and preoperative magnetic resonance images (pMR). We show that this scheme significantly (p << 0.001) reduces tumor boundary misalignment between iUS pre-durotomy and pMR from an average of 2.5 mm to 1.0 mm in six resection surgeries. The corrected tumor alignment before dural opening provides a more accurate reference for assessing subsequent intraoperative tumor displacement, which is important for brain shift compensation as surgery progresses. In addition, we report the translational and rotational capture ranges necessary for successful convergence of the nMI registration technique (5.9 mm and 5.2 deg, respectively). The proposed scheme is automatic, sufficiently robust, and computationally efficient (< 2 min), and holds promise for routine clinical use in the operating room during image-guided neurosurgical procedures. (C) 2008 American Association of Physicists in Medicine. C1 [Ji, Songbai; Hartov, Alex; Paulsen, Keith D.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Wu, Ziji] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hartov, Alex; Roberts, David W.; Paulsen, Keith D.] Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. [Roberts, David W.] Dartmouth Hitchcock Med Ctr, Neurosurg Sect, Lebanon, NH 03756 USA. RP Ji, SB (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. EM Songbai.Ji@Dartmouth.edu FU National Institutes of Health [R01 EB002082-11] FX Funding from the National Institutes of Health Grant No. R01 EB002082-11 is acknowledged. NR 43 TC 34 Z9 35 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2008 VL 35 IS 10 BP 4612 EP 4624 DI 10.1118/1.2977728 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 353TT UT WOS:000259591800036 PM 18975707 ER PT J AU Rafikova, O Salah, EM Tofovic, SP AF Rafikova, Olga Salah, Eman M. Tofovic, Stevan P. TI Renal and metabolic effects of tempol in obese ZSF(1) rats-distinct role for superoxide and hydrogen peroxide in diabetic renal injury SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID IMPROVES INSULIN SENSITIVITY; PERMEABLE RADICAL SCAVENGER; OXIDATIVE STRESS; GLOMERULAR INJURY; ANTIOXIDANT ENZYMES; OXYGEN RADICALS; ORGAN INJURY; NITRIC-OXIDE; DISMUTASE; HYPERTENSION AB Oxidative stress, that is, overproduction of reactive oxygen species and reduced antioxidant system activity, is implicated in the pathogenesis of diabetic complications; and therefore, Superoxide dismutase (SOD) mimetic tempol should be protective in diabetic kidney. However, the effects of tempol in metabolic syndrome-associated renal injury have not been thoroughly examined. In this study, we examined the effects of 9 weeks of treatment with tempol on metabolic status, renal oxidative stress, and kidney function and structure in obese, diabetic, hypertensive ZSF(1) rats and their nondiabetic, hypertensive, lean littermates. The obese rats had significantly reduced total SOD and catalase activity, increased peroxidase activity and lipid peroxidation, and higher level of protein oxidation in renal cortical tissue compared with their lean littermates. These changes were accompanied by renal injury (proteinuria; reduced excretory function; and markedly increased glomerular and interstitial inflammation, proliferation, and collagen IV synthesis). Tempol treatment slightly increased total SOD activity. significantly reduced lipid peroxidation and peroxidase activity, but had no effect on catalase and protein oxidation. Tempol had no effects on blood pressure, renal hemodynamics and excretory function, and proteinuria in obese rats, yet improved insulin sensitivity and reduced renal inflammatory, proliferative, and fibrotic changes. Because tempol possesses no catalase activity and, in diabetes, not only SOD but also catalase is inhibited, it is possible that the toxicity of hydrogen peroxide (H2O2) remains unaltered under tempol treatment. This Study Suggests that superoxide and H2O2 may have distinct roles in the pathogenesis of diabetic renal injury, with superoxide mainly being involved in inflammatory, proliferative, and fibrotic changes, and H2O2 in glomerular hemodynamics and proteinuria. (C) 2008 Elsevier Inc. All rights reserved. C1 [Tofovic, Stevan P.] Univ Pittsburgh, Sch Med, Dept Med, Ctr Clin Pharmacol, Pittsburgh, PA 15219 USA. [Salah, Eman M.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15219 USA. [Salah, Eman M.] VA Pittsburgh Hlth Syst, Pittsburgh, PA 15240 USA. RP Tofovic, SP (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Ctr Clin Pharmacol, Pittsburgh, PA 15219 USA. EM tofovic@dom.pitt.edu NR 51 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 2008 VL 57 IS 10 BP 1434 EP 1444 DI 10.1016/j.metabol.2008.05.014 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 363BI UT WOS:000260240500019 PM 18803950 ER PT J AU Zhou, A Ou, AC Cho, A Benz, EJ Huang, SC AF Zhou, AnYu Ou, Alexander C. Cho, Aeri Benz, Edward J., Jr. Huang, Shu-Ching TI Novel splicing factor RBM25 modulates Bcl-x pre-mRNA 5 ' splice site selection SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID IN-VIVO; SR PROTEINS; ERYTHROID-DIFFERENTIATION; SITE SELECTION; POLYMERASE-II; CELL-DEATH; HNRNP A1; BINDING; REGULATOR; APOPTOSIS AB RBM25 has been shown to associate with splicing cofactors SRm160/300 and assembled splicing complexes, but little is known about its splicing regulation. Here, we characterize the functional role of RBM25 in alternative pre-mRNA splicing. Increased RBM25 expression correlated with increased apoptosis and specifically affected the expression of Bcl-x isoforms. RBM25 stimulated proapoptotic Bcl-xS 5' splice site (5' ss) selection in a dose-dependent manner, whereas its depletion caused the accumulation of antiapoptotic Bcl-x(L). Furthermore, RBM25 specifically bound to Bcl-x RNA through a CGGGCA sequence located within exon 2. Mutation in this element abolished the ability of RBM25 to enhance Bcl-x(S) 5' ss selection, leading to decreased Bcl-x(S) isoform expression. Binding of RBM25 was shown to promote the recruitment of the U1 small nuclear ribonucleoprotein particle (snRNP) to the weak 5' ss; however, it was not required when a strong consensus 5' ss was present. In support of a role for RBM25 in modulating the selection of a 5' ss, we demonstrated that RBM25 associated selectively with the human homolog of yeast U1 snRNP-associated factor hLuc7A. These data suggest a novel mode for Bcl-x(S) 5' ss activation in which binding of RBM25 with exonic element CGGGCA may stabilize the pre-mRNA-U1 snRNP through interactions with hLuc7A. C1 [Zhou, AnYu; Ou, Alexander C.; Cho, Aeri; Benz, Edward J., Jr.; Huang, Shu-Ching] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhou, AnYu; Benz, Edward J., Jr.; Huang, Shu-Ching] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Benz, Edward J., Jr.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Benz, Edward J., Jr.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Benz, Edward J., Jr.] Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. RP Huang, SC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM shu-ching_huang@dfci.harvard.edu FU Claudia Barr Award; NIH [HL24385] FX This work was supported by a Claudia Barr Award (S.C.H.) and NIH grant HL24385 (E.J.B.). NR 56 TC 44 Z9 49 U1 3 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2008 VL 28 IS 19 BP 5924 EP 5936 DI 10.1128/MCB.00560-08 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 350II UT WOS:000259345600009 PM 18663000 ER PT J AU McKenna, ES Sansam, CG Cho, YJ Greulich, H Evans, JA Thom, CS Moreau, LA Biegel, JA Pomeroy, SL Roberts, CWM AF McKenna, Elizabeth S. Sansam, Courtney G. Cho, Yoon-Jae Greulich, Heidi Evans, Julia A. Thom, Christopher S. Moreau, Lisa A. Biegel, Jaclyn A. Pomeroy, Scott L. Roberts, Charles W. M. TI Loss of the epigenetic tumor suppressor SNF5 leads to cancer without genomic instability SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHROMATIN-REMODELING COMPLEX; ATYPICAL TERATOID/RHABDOID TUMORS; MALIGNANT RHABDOID TUMOR; CELL-CYCLE PROGRESSION; CENTRAL-NERVOUS-SYSTEM; EMBRYONIC STEM-CELLS; DNA-DAMAGE RESPONSE; STRAND BREAK REPAIR; CHROMOSOMAL INSTABILITY; GENE-EXPRESSION AB There is a growing appreciation of the role that epigenetic alterations can play in oncogenesis. However, given the large number of genetic anomalies present in most cancers, it has been difficult to evaluate the extent to which epigenetic changes contribute to cancer. SNF5 (INI1/SMARCB1/BAF47) is a tumor suppressor that regulates the epigenome as a core member of the SWI/SNF chromatin remodeling complex. While the SWI/SNF complex displays potent tumor suppressor activity, it is unknown whether this activity is exerted genetically via maintenance of genome integrity or epigenetically via transcriptional regulation. Here we show that Snf5-deficient primary cells do not show altered sensitivity to DNA damaging agents, defects in gamma-H2AX induction, or an abrogated DNA damage checkpoint. Further, the aggressive malignancies that arise following SNF5 loss are diploid and genomically stable. Remarkably, we demonstrate that most human SNF5-deficient cancers lack genomic amplifications/deletions and, aside from SNF5 loss, are indistinguishable from normal cells on single-nucleotide polymorphism arrays. Finally, we show that epigenetically based changes in transcription that occur following SNF5 loss correlate with the tumor phenotype. Collectively, our results provide novel insight into the mechanisms of oncogenesis by demonstrating that disruption of a chromatin remodeling complex can largely, if not completely, substitute for genomic instability in the genesis of aggressive cancer. C1 [McKenna, Elizabeth S.; Sansam, Courtney G.; Evans, Julia A.; Thom, Christopher S.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, Childrens Hosp Boston,Div Hematol Oncol, Boston, MA 02115 USA. [Cho, Yoon-Jae; Pomeroy, Scott L.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Greulich, Heidi] MIT, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02142 USA. [Greulich, Heidi] MIT, Eli & Edythe L Broad Inst, Boston, MA 02142 USA. [Greulich, Heidi] Harvard Univ, Boston, MA 02142 USA. [Biegel, Jaclyn A.] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA. [Moreau, Lisa A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Biegel, Jaclyn A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Roberts, CWM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, Childrens Hosp Boston,Div Hematol Oncol, 44 Binney St Mayer 657, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu FU PHS [F32CA123776, R01CA46274, R01CA109467, R01CA113794]; Garrett B. Smith Foundation; Claudia Adams Barr Foundation; Kate Lambert Rhabdoid Tumor Research Fund; Murphy Family Research Fund; Hope Street Kids FX We thank Tom Curran for providing tumor samples and Yosef Shiloh, Satoshi Tateishi, and Alan D'Andrea for providing the positive-control cell lines for the DNA damage sensitivity assays. We also thank Neil J. Ganem for assistance with the preparation and imaging of mitotic cells, David Pellman and Alan D'Andrea for critical reading of the manuscript, and Rameen Beroukhim for helpful discussions.; The work was supported by PHS awards F32CA123776 ( to C. G. S.), R01CA46274 ( to J. A. B.), R01CA109467 ( to S. L. P.), and R01CA113794 ( to C. W. M. R). C. W. M. R. gratefully acknowledges support from the Garrett B. Smith Foundation, the Claudia Adams Barr Foundation, the Kate Lambert Rhabdoid Tumor Research Fund, and the Murphy Family Research Fund. C. G. S. gratefully acknowledges support from Hope Street Kids.; We declare no competing financial interests. NR 75 TC 59 Z9 61 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2008 VL 28 IS 20 BP 6223 EP 6233 DI 10.1128/MCB.00658-08 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 354JB UT WOS:000259634800007 PM 18710953 ER PT J AU Ilvesaro, JM Merrell, MA Li, L Wakchoure, S Graves, D Brooks, S Rahko, E Jukkola-Vuorinen, A Vuopala, KS Harris, KW Selander, KS AF Ilvesaro, Joanna M. Merrell, Melinda A. Li, Li Wakchoure, Savita Graves, David Brooks, Sonja Rahko, Eeva Jukkola-Vuorinen, Arja Vuopala, Katri S. Harris, Kevin W. Selander, Katri S. TI Toll-Like Receptor 9 Mediates CpG Oligonucleotide-Induced Cellular Invasion SO MOLECULAR CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; BACTERIAL-DNA; SUBCELLULAR-LOCALIZATION; HELICOBACTER-PYLORI; EPITHELIAL-CELLS; IN-VITRO; EXPRESSION; ACTIVATION; TLR9; PATHWAYS AB Toll-like receptor 9 (TLR9) belongs to the innate immune system and recognizes microbial and vertebrate DNA. We showed previously that treatment with the TLR9-agonistic ODN M362 (a CpG sequence containing oligonucleotide) induces matrix metalloproteinase-13-mediated invasion in TLR9-expressing human cancer cell lines. Here, we further characterized the role of the TLR9 pathway in this process. We show that CpG oligonucleotides induce invasion in macrophages from wild-type C57/B6 and MyD88 knockout mice and in human MDA-MB-231 breast cancer cells lacking MyD88 expression. This effect was significantly inhibited in macrophages from TLR9 knockout mice and in human MDA-MB-231 breast cancer cells stably expressing TLR9 small interfering RNA or dominant-negative tumor necrosis factor receptor-associated factor 6 (TRAF6). Sequence modifications to the CpG oligonucleotides that targeted the stem loop and other secondary structures were shown to influence the invasion-inducing effect in MDA-MB-231 cells. In contrast, methylation of the cytosine residues of the parent CpG oligonucleotide did not affect the TLR9-mediated invasion compared with the unmethylated parent CpG oligonucleotide. Finally, expression of TLR9 was studied in clinical breast cancer samples and normal breast epithelium with immunohistochemistry. TLR9 staining localized in epithelial cells in both cancer and normal samples. The mean TLR9 staining intensity was significantly increased in the breast cancer cells compared with normal breast epithelial cells. In conclusion, our results suggest that TLR9 expression is increased in breast cancer and CpG oligonucleotide-induced cellular invasion is mediated via TLR9 and TRAF6, independent of MyD88. Further, our findings suggest that the structure and/or stability of DNA may influence the induction of TLR9-mediated invasion in breast cancer. (Mol Cancer Res 2008;6(10):1534-43) C1 [Ilvesaro, Joanna M.; Merrell, Melinda A.; Li, Li; Wakchoure, Savita; Harris, Kevin W.; Selander, Katri S.] Univ Alabama, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. [Graves, David; Brooks, Sonja] Univ Alabama, Dept Chem, Birmingham, AL 35294 USA. [Harris, Kevin W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Rahko, Eeva; Jukkola-Vuorinen, Arja] Univ Hosp Oulu, Dept Oncol, Oulu, Finland. [Vuopala, Katri S.] Lapland Cent Hosp, Dept Pathol, Rovaniemi, Finland. RP Selander, KS (reprint author), Univ Alabama, Dept Med, Div Hematol Oncol, WT1 T558,1824 6th Ave S, Birmingham, AL 35294 USA. EM Katri.Selander@ccc.uab.edu FU Academy of Finland; Paavo Nurmi Foundation; Finnish Cultural Foundation; Northern Finland Duodecim Foundation FX Academy of Finland, Paavo Nurmi Foundation, Finnish Cultural Foundation (J.M. Ilvesaro), Finnish Cancer Foundation (K.S. Selander), Northern Finland Duodecim Foundation (A. Jukkola-Vuorinen, E. Rahko. and K.S. Selander), and Barry M. Goldwater Scholarship (S. Brooks).; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with IS U.S.C. Section 1734 solely to indicate this fact. NR 49 TC 52 Z9 56 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2008 VL 6 IS 10 BP 1534 EP 1543 DI 10.1158/1541-7786.MCR-07-2005 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 363CS UT WOS:000260244100002 PM 18922969 ER PT J AU Possemato, R Timmons, JC Bauerlein, EL Wada, N Baldwin, A Masutomi, K Hahn, WC AF Possemato, Richard Timmons, Jamie C. Bauerlein, Erica L. Wada, Naoya Baldwin, Amy Masutomi, Kenkichi Hahn, William C. TI Suppression of hPOT1 in Diploid Human Cells Results in an hTERT-Dependent Alteration of Telomere Length Dynamics SO MOLECULAR CANCER RESEARCH LA English DT Article ID ABERRANT HOMOLOGOUS RECOMBINATION; DNA-DAMAGE RESPONSE; HUMAN TUMOR-CELLS; IN-VITRO; INDUCED SENESCENCE; HUMAN FIBROBLASTS; DYSFUNCTIONAL TELOMERES; CELLULAR SENESCENCE; PROTECTS TELOMERES; IMMORTAL CELLS AB POT1 is a 3'telomeric single-stranded overhang binding protein that has been implicated in chromosome end protection, the regulation of telomerase function, and defining the 5' chromosome terminus. In human cancer cells that exhibit constitutive hTERT activity, hPOT1 exerts control over telomere length. Primary human fibroblasts express low levels of catalytically active hTERT in an S-phase-restricted manner that fails to counteract telomere attrition with cell division. Here, we show that diploid human fibroblasts in which hPOT1 expression has been suppressed harbor telomeres that are longer than control cells. This difference in telomere length delays the onset of replicative senescence and is dependent on S-phase-restricted hTERT expression. These findings are consistent with the view that hPOT1 promotes a nonextendable telomere state resistant to extension by S-phase-restricted telomerase. Manipulating this function of hPOT1 may thus hasten the cytotoxic effects of telomerase inhibition. (Mol Cancer Res 2008;6(10):1582-93) C1 [Possemato, Richard; Timmons, Jamie C.; Bauerlein, Erica L.; Wada, Naoya; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Possemato, Richard; Timmons, Jamie C.; Bauerlein, Erica L.; Wada, Naoya; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Baldwin, Amy] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Baldwin, Amy] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Hahn, William C.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Hahn, William C.] MIT, Cambridge, MA 02139 USA. [Masutomi, Kenkichi] Natl Canc Ctr, Canc Stem Cell Project, Tokyo 104, Japan. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu OI Possemato, Richard/0000-0002-2401-0030 FU NIH National Institute on Aging [R01 AG23145]; Howard Hughes FX NIH National Institute on Aging grant R01 AG23145 and Johnson and Johnson Focused Giving Program Award. R. Possernato was supported by a Howard Hughes Predoctoral Fellowship.; The Costs Of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 64 TC 8 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2008 VL 6 IS 10 BP 1582 EP 1593 DI 10.1158/1541-7786.MCR-08-0070 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 363CS UT WOS:000260244100007 PM 18922974 ER PT J AU Basak, S Pookot, D Noonan, EJ Dahiya, R AF Basak, Shashwati Pookot, Deepa Noonan, Emily J. Dahiya, Rajvir TI Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PROSTATE-CANCER CELLS; HISTONE DEACETYLASE INHIBITORS; TUMOR-SUPPRESSOR GENES; NF-KAPPA-B; BREAST-CANCER; UP-REGULATION; IN-VIVO; EXPRESSION; APOPTOSIS; HEAT-SHOCK-PROTEIN-90 AB Androgen receptor (AR) is a ligand-activated transcription factor belonging to the steroid hormone receptor family and is very important for the development and progression of prostate cancer. The soy isoflavone genistein has been shown previously to down-regulate AR in androgen-dependent prostate cancer cell lines such as LNCaP. However, the mechanism(s) by which AR is down-regulated by genistein is still not known fully. We show a new mechanism by which genistein inhibits AR protein levels. We show that genistein-treated LNCaP cells exhibit increased ubiquitination of AR, suggesting that AR protein is down-regulated via a proteasome-mediated pathway. AR is normally stabilized by the chaperone activity of the heat shock protein Hsp90. The increased ubiquitination of AR after genistein treatment is attributed to decreased Hsp90 chaperone activity as assessed by its increased functionally inactive acetylated form. Consistent with this result, we find that HDAC6, which is a Hsp90 deacetylase, is inhibited by the antiestrogenic activity of genistein. Hence, in this study, we elucidate a novel mechanism of AR down-regulation by genistein through inhibition of HDAC6-Hsp90 cochaperone function required to stabilize AR protein. Our results suggest that genistein could be used as a potential chemopreventive agent for prostate cancers along with known inhibitors of HDAC6 and Hsp90. [Mol Cancer Ther 2008;7(10):3195-202] C1 [Dahiya, Rajvir] San Francisco VA Med Ctr, Urol Res Ctr 112F, Dept Urol, San Francisco, CA 94121 USA. [Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Dahiya, R (reprint author), San Francisco VA Med Ctr, Urol Res Ctr 112F, Dept Urol, 4150 Clement St, San Francisco, CA 94121 USA. EM Rdahiya@urology.ucsf.edu FU NIH [NIHNCI R01CA 111470, T32DK007790]; VA Merit Review and Research Enhancement Award FX Grant support: NIH grants NIHNCI R01CA 111470 and T32DK007790; VA Merit Review and Research Enhancement Award Program (Principal Investigator: R. Dahiya). NR 46 TC 62 Z9 64 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2008 VL 7 IS 10 BP 3195 EP 3202 DI 10.1158/1535-7163.MCT-08-0617 PG 8 WC Oncology SC Oncology GA 362MO UT WOS:000260202000009 PM 18852123 ER PT J AU Lu, Y Nie, DB Witt, WT Chen, QY Shen, M Xie, HY Lai, LX Dai, YF Zhang, J AF Lu, Yi Nie, Daibang Witt, William T. Chen, Qiuyan Shen, Miaoda Xie, Haiyang Lai, Liangxue Dai, Yifan Zhang, Jian TI Expression of the fat-1 gene diminishes prostate cancer growth in vivo through enhancing apoptosis and inhibiting GSK-30 phosphorylation SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ESSENTIAL FATTY-ACIDS; BETA-CATENIN; TRANSGENIC MICE; CELLS; OMEGA-3-FATTY-ACIDS; ACCUMULATION; MODULATION; MECHANISMS; RATIOS; RISK AB Epidemiologic studies inclusively indicate that "unhealthy" dietary fat intake is one of the potential risk factors for cancer. In dietary fat, there are two types of polyunsaturated fatty acids (PUFA), omega-3 (n-3) and omega-6 (n-6). Numerous studies support that the ratio of n-6/n-3 affects tumorigenesis. It was reported that adenoviral transfer of the fat-1 gene, which converts n-6 to n-3, into breast and lung cancer cells had an antitumor effect in vitro. However, the effects of the fat-1 gene expression on tumor growth in vivo have not been studied and the mechanisms remain unclear. Accordingly, prostate cancer DU145 and PC3 cells were transfected with either the fat-1 gene or a control vector. The cells that expressed the fat-1 gene had a lower n-6/n-3 PUFA ratio compared with the cells that expressed the control vector. The fat-1 gene expression significantly inhibited prostate cancer cell proliferation and invasion in vitro. The fat-1 and control vector-transfected prostate cancer cells were s.c. implanted into severe combined immunodeficient mice for 6 weeks. The fat-1 gene expression significantly diminished tumor growth in vivo, but the control vector had no effect. Finally, we evaluated signaling pathways that may be important for fat-1 gene function. Administration of n-3 PUFA induced caspase-3-mediated prostate cancer cell apoptosis in vitro. The fat-1 gene expression inhibited prostate cancer cell proliferation via reduction of GSK-3 beta phosphorylation and subsequent down-regulation of both beta-catenin and cyclin D1. These results suggest that fat-1 gene transfer directly into tumor cells could be used as a novel therapeutic approach. [Mol Cancer Ther 2008;7(10):3203-11] C1 [Zhang, Jian] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA 15240 USA. [Witt, William T.; Shen, Miaoda; Xie, Haiyang; Dai, Yifan] Thomas E Starzl Transplantat Inst, Dept Surg, Pittsburgh, PA USA. [Nie, Daibang; Lai, Liangxue] Jilin Univ, Coll Anim Sci & Vet Technol, Changchun 130023, Peoples R China. RP Zhang, J (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Dept Med, Room 2E146,Univ Dr, Pittsburgh, PA 15240 USA. EM daiy@upmc.edu; zhangj2@upmc.edu FU Department of Defense [PC061231]; University of Pittsburgh Cancer Institute CCSG FX Grant support: Department of Defense PC061231 and University of Pittsburgh Cancer Institute CCSG (J. Zhang). NR 28 TC 29 Z9 29 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2008 VL 7 IS 10 BP 3203 EP 3211 DI 10.1158/1535-7163.MCT-08-0494 PG 9 WC Oncology SC Oncology GA 362MO UT WOS:000260202000010 PM 18852124 ER PT J AU Davis, AE Mejia, P Lu, FX AF Davis, Alvin E., III Mejia, Pedro Lu, Fengxin TI Biological activities of C1 inhibitor SO MOLECULAR IMMUNOLOGY LA English DT Article; Proceedings Paper CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND DE Complement system; Plasma kallikrein-kinin system; Serpins; Gram negative sepsis; Ischemia-reperfusion injury; Hyperacute transplant rejection; Leukocyte rolling ID ISCHEMIA-REPERFUSION INJURY; ELEVATION MYOCARDIAL-INFARCTION; ESCHERICHIA-COLI O157-H7; N-LINKED GLYCOSYLATION; CL-ESTERASE INHIBITOR; C1-ESTERASE INHIBITOR; PLASMA KALLIKREIN; COMPLEMENT COMPONENT; HYPERACUTE REJECTION; ENDOTOXIN-SHOCK AB Broadly speaking, C1 inhibitor plays important roles in the regulation of vascular permeability and in the suppression of inflammation. Vascular permeability control is exerted largely through inhibition of two of the proteases involved in the generation of bradykinin, factor XIIa and plasma kallikFein (the plasma kallikrein-kinin system). Anti-inflammatory functions, however, are exerted via several activities including inhibition of complement system protease (C1r, C1s, MASP2) and the plasma kallikrein-kinin system proteases, in addition to interactions with a number of different Proteins, cells and infectious agents. These more recently described, as yet incompletely characterized, activities serve several potential functions, including concentration of C1 inhibitor at sites of inflammation, inhibition of alternative complement pathway activation, inhibition of the biologic activities of gram negative endotoxin, enhancement of bacterial phagocytosis and killing, and suppression of the influx of leukocytes into a site of inflammation. C I inhibitor has been shown to be therapeutically useful in a variety of animal models of inflammatory diseases, including gram negative bacterial sepsis and endotoxin shock, suppression of hyperacute transplant rejection, and treatment of a variety of ischemia-reperfusion injuries (heart, intestine, skeletal muscle, liver, brain). In humans, early data appear particularly promising in myocardial reperfusion injury. The mechanism (or mechanisms) of the effect of C1 inhibitor in these conditions is (are) not completely clear, but involve inhibition of complement and contact system activation, in addition to variable contributions from other C1 inhibitor activities that do not involve protease inhibition. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Davis, Alvin E., III; Mejia, Pedro; Lu, Fengxin] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM aldavis@idi.harvard.edu FU NIAID NIH HHS [R01 AI057366, R01 AI057366-04, R01-AI057366]; NICHD NIH HHS [R37-HD22082, R37 HD022082, R37 HD022082-23] NR 106 TC 93 Z9 95 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI BP 4057 EP 4063 DI 10.1016/j.molimm.2008.06.028 PG 7 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000003 PM 18674818 ER PT J AU Barrington, RA Schneider, TJ Pitcher, L Carroll, M AF Barrington, R. A. Schneider, T. J. Pitcher, L. Carroll, Michael TI Uncoupling CD21 and CD19 of the B cell co-receptor SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND C1 [Barrington, R. A.; Schneider, T. J.; Pitcher, L.; Carroll, Michael] Immune Dis Inst, Boston, MA USA. [Carroll, Michael] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI MA O33 BP 4106 EP 4106 DI 10.1016/j.molimm.2008.08.034 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000041 ER PT J AU Roosendahl, RR Memphel, T Pitcher, L Gonzalez, S Carroll, M AF Roosendahl, R. R. Memphel, T. Pitcher, L. Gonzalez, S. Carroll, Michael TI Trafficking of complement-tagged antigens in lymph nodes SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND C1 [Roosendahl, R. R.; Pitcher, L.; Gonzalez, S.; Carroll, Michael] Immune Dis Inst, Boston, MA USA. [Memphel, T.] Harvard Univ, Sch Med, MGH, Boston, MA USA. [Memphel, T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Memphel, T.; Pitcher, L.; Carroll, Michael] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI MA O32 BP 4106 EP 4106 DI 10.1016/j.molimm.2008.08.033 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000040 ER PT J AU Gonzalez, SF Jayasekera, J Carroll, M AF Gonzalez, Santiago F. Jayasekera, Jerome Carroll, Michael TI The role of complement and natural antibody in the long-term memory response to influenza virus SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND C1 [Gonzalez, Santiago F.; Jayasekera, Jerome; Carroll, Michael] IDI Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI MA P143 BP 4142 EP 4142 DI 10.1016/j.molimm.2008.08.142 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000149 ER PT J AU Tsiftsoglou, SA Alimzhanov, MB Carroll, MC AF Tsiftsoglou, Stefanos A. Alimzhanov, Marat B. Carroll, Michael C. TI Identification of rRNA as a lupus antigen SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND C1 [Tsiftsoglou, Stefanos A.; Alimzhanov, Marat B.; Carroll, Michael C.] Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI MA P153 BP 4146 EP 4146 DI 10.1016/j.molimm.2008.08.152 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000159 ER PT J AU Lu, FX Chauhan, A Fernandes, S Walsh, M Wagner, D Wagner, D Davis, A AF Lu, Fengxin Chauhan, Anil Fernandes, Stacey Walsh, Meghan Wagner, Denisa Wagner, Denisa Davis, Alvin, III TI The effect of C1 inhibitor on intestinal ischaemia and reperfusion injury SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND C1 [Lu, Fengxin; Chauhan, Anil; Fernandes, Stacey; Walsh, Meghan; Wagner, Denisa; Wagner, Denisa; Davis, Alvin, III] Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI MA P182 BP 4156 EP 4156 DI 10.1016/j.molimm.2008.08.181 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000188 ER PT J AU Mejia, P Davis, A AF Mejia, Pedro Davis, Alvin, III TI C1 inhibitor mediated protection from Gram-negative endotoxin shock varies with the level of LPS binding SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND C1 [Mejia, Pedro; Davis, Alvin, III] Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI MA P183 BP 4156 EP 4156 DI 10.1016/j.molimm.2008.08.182 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000189 ER PT J AU Mejia, P Diez-Silva, M Lu, FX Davis, A AF Mejia, Pedro Diez-Silva, Monica Lu, Fengxin Davis, Alvin, III TI C1 inhibitor interacts with Plasmodium falciparum and protects against experimental severe malaria in mice SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND C1 [Mejia, Pedro; Lu, Fengxin; Davis, Alvin, III] Immune Dis Inst, Boston, MA USA. [Diez-Silva, Monica] MIT, Cambridge, MA 02139 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI MA P184 BP 4156 EP 4156 DI 10.1016/j.molimm.2008.08.183 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000190 ER PT J AU Haas, M Zheng, Y Schuerpf, F Alicot-Carroll, E Carroll, M AF Haas, Michael Zheng, Yi Schuerpf, Franziska Alicot-Carroll, Elisabeth Carroll, Michael TI Human natural IgM mediates injury in a murine model of myocardial infarction SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND C1 [Alicot-Carroll, Elisabeth] Declmmune Therapeut Inc, Immune Dis Inst, Boston, MA USA. [Carroll, Michael] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI MA P197 BP 4161 EP 4161 DI 10.1016/j.molimm.2008.08.196 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000203 ER PT J AU Chiu, IM Kosaras, B Tsiftsoglou, SA Zhang, M Vartanian, TK Carroll, MC AF Chiu, Isaac M. Kosaras, Bela Tsiftsoglou, Stefanos A. Zhang, Ming Vartanian, Timothy K. Carroll, Michael C. TI Complement activation in a mouse model of amyotrophic lateral sclerosis SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND C1 [Chiu, Isaac M.; Tsiftsoglou, Stefanos A.; Zhang, Ming; Carroll, Michael C.] Immune Dis Inst, Boston, MA USA. [Kosaras, Bela; Vartanian, Timothy K.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. OI ZHANG, MING/0000-0002-5836-0960 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI MA P204 BP 4163 EP 4163 DI 10.1016/j.molimm.2008.08.203 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000210 ER PT J AU Michelowa, I Olinger, G Spear, G Yantosca, L Jil, X Takahashi, K Schmidt, E AF Michelowa, Ian Olinger, Gene Spear, Gregory Yantosca, Louis Jil, Xin Takahashi, Kazue Schmidt, Emmett TI Control of Ebola virus infection in mice with recombinant human mannose-binding lectin: Requirement for C3 SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND C1 [Michelowa, Ian; Yantosca, Louis; Takahashi, Kazue; Schmidt, Emmett] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Olinger, Gene] USAMRID, Frederick, MD USA. [Spear, Gregory; Jil, Xin] Rush Univ, Med Ctr, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI MA P206 BP 4164 EP 4164 DI 10.1016/j.molimm.2008.08.205 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000212 ER PT J AU Takahashi, K McClear, S Stahl, G AF Takahashi, Kazue McClear, Sheree Stahl, Gregory TI Relative roles of complement pathways in Staphylococcus aureus infection SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 22nd International Complement Workshop CY SEP 28-OCT 02, 2008 CL Basel, SWITZERLAND C1 [Takahashi, Kazue; McClear, Sheree] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Stahl, Gregory] Harvard Univ, Sch Med, BWH, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2008 VL 45 IS 16 SI SI MA P211 BP 4165 EP 4165 DI 10.1016/j.molimm.2008.08.210 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 363DB UT WOS:000260245000217 ER PT J AU Maguire, CA Meijer, DH Leroy, SG Tierney, LA Broekman, MLD Costa, FF Breakefield, XO Stemmer-Rachamimov, A Sena-Esteves, M AF Maguire, Casey A. Meijer, Dimphna H. Leroy, Stanley G. Tierney, Laryssa A. Broekman, Marike L. D. Costa, Fabricio F. Breakefield, Xandra O. Stemmer-Rachamimov, Anat Sena-Esteves, Miguel TI Preventing growth of brain tumors by creating a zone of resistance SO MOLECULAR THERAPY LA English DT Article ID ADENOASSOCIATED VIRUS VECTORS; BETA GENE-THERAPY; CONVECTION-ENHANCED DELIVERY; INTERFERON-SS GENE; HUMAN GLIOMA; MOUSE-BRAIN; MALIGNANT GLIOMAS; RETROVIRAL VECTORS; VIRAL VECTORS; IN-VIVO AB Glioblastoma multiforme (GBM) is a devastating form of brain cancer for which there is no effective treatment. Here, we report a novel approach to brain tumor therapy through genetic modification of normal brain cells to block tumor growth and effect tumor regression. Previous studies have focused on the use of vector-based gene therapy for GBM by direct intratumoral injection with expression of therapeutic proteins by tumor cells themselves. However, as antitumor proteins are generally lethal to tumor cells, the therapeutic reservoir is rapidly depleted, allowing escape of residual tumor cells. Moreover, it has been difficult to achieve consistent transduction of these highly heterogeneous tumors. In our studies, we found that transduction of normal cells in the brain with an adeno-associated virus (AAV) vector encoding interferon-beta (IFN-beta) was sufficient to completely prevent tumor growth in orthotopic xenograft models of GBM, even in the contralateral hemisphere. In addition, complete eradication of established tumors was achieved through expression of IFN-beta by neurons using a neuronal-restricted promoter. To our knowledge this is the first direct demonstration of the efficacy of targeting gene delivery exclusively to normal brain cells for brain tumor therapy. C1 [Maguire, Casey A.; Meijer, Dimphna H.; Leroy, Stanley G.; Tierney, Laryssa A.; Costa, Fabricio F.; Breakefield, Xandra O.; Sena-Esteves, Miguel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. [Maguire, Casey A.; Meijer, Dimphna H.; Leroy, Stanley G.; Tierney, Laryssa A.; Costa, Fabricio F.; Breakefield, Xandra O.; Sena-Esteves, Miguel] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02129 USA. [Meijer, Dimphna H.; Broekman, Marike L. D.] UMC Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurosci & Pharmacol, Utrecht, Netherlands. [Broekman, Marike L. D.] Univ Med Ctr Utrecht, Dept Neurosurg, Utrecht, Netherlands. [Stemmer-Rachamimov, Anat] Harvard Univ, Sch Med, Mol Neurooncol Lab, Boston, MA 02129 USA. [Stemmer-Rachamimov, Anat] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Sena-Esteves, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 149 13th St, Boston, MA 02129 USA. EM msesteves@partners.org FU Alliance for Cancer Gene Therapy; National Institutes of Health (NIH) [CA69246, CA073479-09]; Massachusetts General Hospital (MGH) FX This work was supported by a Young Investigator Award from the Alliance for Cancer Gene Therapy (to M. S. E.), National Institutes of Health (NIH) CA69246 (to X.O.B.), and NIH 5 T32 CA073479-09 (to C. M.). We acknowledge Rakesh Jain and the Edwin L. Steele Laboratory at Massachusetts General Hospital (MGH) for support during this study. Also, we acknowledge the MGH Neuroscience Center Microscopy and Image Analysis Core (NIH grant P30NS045776) for the use of the Nikon scanner, and Ralph Weissleder, Director of the Center for Molecular Imaging Research, for the use of the bioluminescence imager, Katy Bercury and Bradley Hyman for kindly providing the primary murine neuronal cultures, and Jeffrey Hewett for technical advice on the immunoblot experiments. Finally, we thank Johan Skog, Bakhos Tannous, and Okay Saydam for critical reading of the manuscript. NR 49 TC 24 Z9 24 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD OCT PY 2008 VL 16 IS 10 BP 1695 EP 1702 DI 10.1038/mt.2008.168 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 356RW UT WOS:000259796300008 PM 18714312 ER PT J AU Kahvejian, A Quackenbush, J Thompson, JF AF Kahvejian, Avak Quackenbush, John Thompson, John F. TI What would you do if you could sequence everything? SO NATURE BIOTECHNOLOGY LA English DT Review ID GENOME-WIDE ASSOCIATION; HUMAN EPIGENOME PROJECT; EMBRYONIC STEM-CELLS; PROTEIN-DNA INTERACTIONS; MULTIPLE RARE ALLELES; COPY-NUMBER VARIATION; GENE-EXPRESSION; HIGH-RESOLUTION; COLORECTAL CANCERS; HUMAN BREAST AB It could be argued that the greatest transformative aspect of the Human Genome Project has been not the sequencing of the genome itself, but the resultant development of new technologies. A host of new approaches has fundamentally changed the way we approach problems in basic and translational research. Now, a new generation of high-throughput sequencing technologies promises to again transform the scientific enterprise, potentially supplanting array-based technologies and opening up many new possibilities. By allowing DNA/RNA to be assayed more rapidly than previously possible, these next-generation platforms promise a deeper understanding of genome regulation and biology. Significantly enhancing sequencing throughput will allow us to follow the evolution of viral and bacterial resistance in real time, to uncover the huge diversity of novel genes that are currently inaccessible, to understand nucleic acid therapeutics, to better integrate biological information for a complete picture of health and disease at a personalized level and to move to advances that we cannot yet imagine. C1 [Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kahvejian, Avak; Thompson, John F.] Helicos BioSci, Cambridge, MA 02139 USA. RP Quackenbush, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM johnq@jimmy.harvard.edu OI Thompson, John/0000-0001-8568-3311 FU NLM NIH HHS [R01 LM010129] NR 112 TC 102 Z9 109 U1 1 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2008 VL 26 IS 10 BP 1125 EP 1133 DI 10.1038/nbt1494 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 358NY UT WOS:000259926000027 PM 18846086 ER PT J AU Misra, M AF Misra, Madhusmita TI What is the best strategy to combat low bone mineral density in functional hypothalamic amenorrhea? SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material DE androgen; anorexia nervosa; athlete; estrogen; insulin-like growth factor 1 ID ANOREXIA-NERVOSA; DOUBLE-BLIND; WEIGHT-GAIN; TRIAL; WOMEN AB Functional hypothalamic amenorrhea (FHA) is associated with low BMD and decreased rates of bone mass accrual, particularly in conditions of severe undernutrition, such as anorexia nervosa. In addition to immediate fracture risk, the finding of impaired bone metabolism in young women raises concerns about reduced peak bone mass, an important determinant of bone health in later life. Appropriate treatment of FHA is, therefore, crucial for restoration of BM D and for bone mass accrual. Vescovi et al. have performed a systematic review of the literature in order to assess therapeutic strategies that aim to reverse bone loss in women with FHA. In this Practice Point commentary, I discuss the extent to which hormonal and nonhormonal therapies have, or have not, been beneficial in optimizing bone health. In addition, I emphasize the importance of weight gain and recovery of reproductive function in the preservation of bone health in women with FHA. C1 [Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU NCRR NIH HHS [K23 RR018851] NR 7 TC 3 Z9 3 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD OCT PY 2008 VL 4 IS 10 BP 542 EP 543 DI 10.1038/ncpendmet0925 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 349QB UT WOS:000259294600005 PM 18679386 ER PT J AU Baehring, JM Hochberg, EP Raje, N Urickson, M Hochberg, FH AF Baehring, Joachim M. Hochberg, Ephraim P. Raje, Noopur Urickson, Matthew Hochberg, Fred H. TI Neurological manifestations of Waldenstrom macroglobulinemia SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Review DE hyperviscosity; neuropathy; monoclonal gammopathies; monoclonal gammopathy of unknown significance; Waldenstroms macroglobulinemia ID BING-NEEL-SYNDROME; CENTRAL-NERVOUS-SYSTEM; IGM MONOCLONAL GAMMOPATHY; CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; B-CELL LYMPHOMA; PERIPHERAL NEUROPATHY; LYMPHOPLASMACYTIC LYMPHOMA; UNDETERMINED SIGNIFICANCE; PROGNOSTIC FACTORS AB Waldenstrom macroglobulinemia, a condition that most commonly occurs in lymphoplasmacytic lymphoma, typically manifests with diffuse lymphadenopathies, cytopenias, and a markedly elevated erythrocyte sedimentation rate. Peripheral neuropathy occurs in nearly half of patients with this condition, and hyperviscosity-related nervous system disorders are encountered in up to a third. Other neurological complications, such as encephalopathy or myelopathy caused by direct tumor infiltration, paraprotein deposition or autoimmune phenomena, are rare. Diagnosis of Waldenstrom macroglobulinemia requires identification of monoclonal IgM protein in the serum, bone marrow biopsy, and appropriate neurological testing (e.g. imaging studies of affected areas of the central neuraxis, electrophysiological studies). Treatment options, which should address both the paraprotein burden and the lymphoplasmacytic clone, include plasmapheresis and chemotherapy with alkylating agents, nucleoside analogs, and rituximab. As the disease is incurable and its Course indolent, these treatments are only provided to symptomatic patients. C1 [Hochberg, Fred H.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Baehring, Joachim M.] Yale Univ, Sch Med, New Haven, CT USA. [Baehring, Joachim M.] Yale Brain Tumor Ctr, New Haven, CT USA. RP Hochberg, FH (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9010, Boston, MA 02114 USA. EM flhochberg@partners.org NR 92 TC 21 Z9 22 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD OCT PY 2008 VL 4 IS 10 BP 547 EP 556 DI 10.1038/ncpneuro0917 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 354CD UT WOS:000259615600011 PM 18813229 ER PT J AU McCarroll, SA Kuruvilla, FG Korn, JM Cawley, S Nemesh, J Wysoker, A Shapero, MH de Bakker, PIW Maller, JB Kirby, A Elliott, AL Parkin, M Hubbell, E Webster, T Mei, R Veitch, J Collins, PJ Handsaker, R Lincoln, S Nizzari, M Blume, J Jones, KW Rava, R Daly, MJ Gabriel, SB Altshuler, D AF McCarroll, Steven A. Kuruvilla, Finny G. Korn, Joshua M. Cawley, Simon Nemesh, James Wysoker, Alec Shapero, Michael H. de Bakker, Paul I. W. Maller, Julian B. Kirby, Andrew Elliott, Amanda L. Parkin, Melissa Hubbell, Earl Webster, Teresa Mei, Rui Veitch, James Collins, Patrick J. Handsaker, Robert Lincoln, Steve Nizzari, Marcia Blume, John Jones, Keith W. Rava, Rich Daly, Mark J. Gabriel, Stacey B. Altshuler, David TI Integrated detection and population-genetic analysis of SNPs and copy number variation SO NATURE GENETICS LA English DT Article ID HUMAN GENOME; STRUCTURAL VARIATION; LINKAGE DISEQUILIBRIUM; DELETION POLYMORPHISM; HAPLOTYPE MAP; VARIANTS; DISEASE AB Dissecting the genetic basis of disease risk requires measuring all forms of genetic variation, including SNPs and copy number variants (CNVs), and is enabled by accurate maps of their locations, frequencies and population-genetic properties. We designed a hybrid genotyping array (Affymetrix SNP 6.0) to simultaneously measure 906,600 SNPs and copy number at 1.8 million genomic locations. By characterizing 270 HapMap samples, we developed a map of human CNV (at 2-kb breakpoint resolution) informed by integer genotypes for 1,320 copy number polymorphisms (CNPs) that segregate at an allele frequency >1%. More than 80% of the sequence in previously reported CNV regions fell outside our estimated CNV boundaries, indicating that large (>100 kb) CNVs affect much less of the genome than initially reported. Approximately 80% of observed copy number differences between pairs of individuals were due to common CNPs with an allele frequency >5%, and more than 99% derived from inheritance rather than new mutation. Most common, diallelic CNPs were in strong linkage disequilibrium with SNPs, and most low-frequency CNVs segregated on specific SNP haplotypes. C1 [McCarroll, Steven A.; Kuruvilla, Finny G.; Korn, Joshua M.; Nemesh, James; Wysoker, Alec; de Bakker, Paul I. W.; Elliott, Amanda L.; Parkin, Melissa; Handsaker, Robert; Nizzari, Marcia; Daly, Mark J.; Gabriel, Stacey B.; Altshuler, David] MIT, Broad Inst, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA 02142 USA. [McCarroll, Steven A.; Kuruvilla, Finny G.; Korn, Joshua M.; Nemesh, James; Wysoker, Alec; de Bakker, Paul I. W.; Elliott, Amanda L.; Parkin, Melissa; Handsaker, Robert; Nizzari, Marcia; Daly, Mark J.; Gabriel, Stacey B.; Altshuler, David] Harvard Univ, Cambridge, MA 02142 USA. [McCarroll, Steven A.; Kuruvilla, Finny G.; Korn, Joshua M.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [McCarroll, Steven A.; Kuruvilla, Finny G.; Korn, Joshua M.; Maller, Julian B.; Kirby, Andrew; Daly, Mark J.; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [McCarroll, Steven A.; Kuruvilla, Finny G.; de Bakker, Paul I. W.; Daly, Mark J.; Altshuler, David] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Korn, Joshua M.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Korn, Joshua M.] Harvard Univ, Grad Program Biophys, Cambridge, MA 02138 USA. [Cawley, Simon; Shapero, Michael H.; Hubbell, Earl; Webster, Teresa; Mei, Rui; Veitch, James; Collins, Patrick J.; Lincoln, Steve; Blume, John; Jones, Keith W.; Rava, Rich] Affymetrix Inc, Santa Clara, CA 95051 USA. [de Bakker, Paul I. W.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Partners HealthCare Syst Ctr Genet & Genom, Boston, MA 02115 USA. [Daly, Mark J.; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP McCarroll, SA (reprint author), MIT, Broad Inst, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA 02142 USA. EM smccarro@broad.mit.edu; altshuler@molbio.mgh.harvard.edu RI McCarroll, Steven/A-8433-2009; Altshuler, David/A-4476-2009; Elliott, Amanda/G-5120-2012; de Bakker, Paul/B-8730-2009; OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Maller, Julian/0000-0002-1565-9559; McCarroll, Steven/0000-0002-6954-8184 NR 29 TC 565 Z9 582 U1 2 U2 49 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2008 VL 40 IS 10 BP 1166 EP 1174 DI 10.1038/ng.238 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 354PH UT WOS:000259651000015 PM 18776908 ER PT J AU Raychaudhuri, S Remmers, EF Lee, AT Hackett, R Guiducci, C Burtt, NP Gianniny, L Korman, BD Padyukov, L Kurreeman, FAS Chang, M Catanese, JJ Ding, B Wong, S Mil, AHMV Neale, BM Coblyn, J Cui, J Tak, PP Wolbink, GJ Crusius, JBA van der Horst-Bruinsma, IE Criswell, LA Amos, CI Seldin, MF Kastner, DL Ardlie, KG Alfredsson, L Costenbader, KH Altshuler, D Huizinga, TWJ Shadick, NA Weinblatt, ME de Vries, N Worthington, J Seielstad, M Toes, REM Karlson, EW Begovich, AB Klareskog, L Gregersen, PK Daly, MJ Plenge, RM AF Raychaudhuri, Soumya Remmers, Elaine F. Lee, Annette T. Hackett, Rachel Guiducci, Candace Burtt, Noel P. Gianniny, Lauren Korman, Benjamin D. Padyukov, Leonid Kurreeman, Fina A. S. Chang, Monica Catanese, Joseph J. Ding, Bo Wong, Sandra Mil, Annette H. M. van der Helm-van Neale, Benjamin M. Coblyn, Jonathan Cui, Jing Tak, Paul P. Wolbink, Gert Jan Crusius, J. Bart A. van der Horst-Bruinsma, Irene E. Criswell, Lindsey A. Amos, Christopher I. Seldin, Michael F. Kastner, Daniel L. Ardlie, Kristin G. Alfredsson, Lars Costenbader, Karen H. Altshuler, David Huizinga, Tom W. J. Shadick, Nancy A. Weinblatt, Michael E. de Vries, Niek Worthington, Jane Seielstad, Mark Toes, Rene E. M. Karlson, Elizabeth W. Begovich, Ann B. Klareskog, Lars Gregersen, Peter K. Daly, Mark J. Plenge, Robert M. TI Common variants at CD40 and other loci confer risk of rheumatoid arthritis SO NATURE GENETICS LA English DT Article ID NF-KAPPA-B; SINGLE-NUCLEOTIDE POLYMORPHISM; GENOME-WIDE ASSOCIATION; GRAVES-DISEASE; SUSCEPTIBILITY; GENE; COOPERATION; EXPRESSION; INTERACTS; ANTIBODY AB To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls(1,2). We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall). C1 [Raychaudhuri, Soumya; Hackett, Rachel; Guiducci, Candace; Burtt, Noel P.; Gianniny, Lauren; Wong, Sandra; Neale, Benjamin M.; Ardlie, Kristin G.; Altshuler, David; Daly, Mark J.; Plenge, Robert M.] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Raychaudhuri, Soumya; Hackett, Rachel; Guiducci, Candace; Burtt, Noel P.; Gianniny, Lauren; Wong, Sandra; Neale, Benjamin M.; Ardlie, Kristin G.; Altshuler, David; Daly, Mark J.; Plenge, Robert M.] MIT, Cambridge, MA 02142 USA. [Raychaudhuri, Soumya; Coblyn, Jonathan; Cui, Jing; Costenbader, Karen H.; Shadick, Nancy A.; Weinblatt, Michael E.; Karlson, Elizabeth W.; Plenge, Robert M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Raychaudhuri, Soumya; Neale, Benjamin M.; Altshuler, David; Daly, Mark J.; Plenge, Robert M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Remmers, Elaine F.; Korman, Benjamin D.; Kastner, Daniel L.] NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. [Lee, Annette T.; Gregersen, Peter K.] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Padyukov, Leonid; Klareskog, Lars] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden. [Kurreeman, Fina A. S.; Mil, Annette H. M. van der Helm-van; Huizinga, Tom W. J.; Toes, Rene E. M.] Leiden Univ, Med Ctr, Dept Rheumatol, NL-2333 ZA Leiden, Netherlands. [Chang, Monica; Catanese, Joseph J.; Begovich, Ann B.] Celera, Alameda, CA 94502 USA. [Ding, Bo; Alfredsson, Lars] Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden. [Neale, Benjamin M.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [Tak, Paul P.] Univ Amsterdam, Acad Med Ctr, NL-326 Amsterdam, Netherlands. [Wolbink, Gert Jan] Jan van Breemen Inst, NL-1056 AB Amsterdam, Netherlands. [Wolbink, Gert Jan] Univ Amsterdam, Acad Med Ctr, Sanquin Res Landsteiner Lab, NL-1006 AD Amsterdam, Netherlands. [van der Horst-Bruinsma, Irene E.] Vrije Univ Amsterdam, Med Ctr, Dept Rheumatol, NL-1007 MB Amsterdam, Netherlands. [Crusius, J. Bart A.] Vrije Univ Amsterdam, Med Ctr, Immunogenet Lab, Dept Pathol, NL-1007 MB Amsterdam, Netherlands. [Criswell, Lindsey A.] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 94143 USA. [Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Seldin, Michael F.] Univ Calif Davis, Rowe Program Genet, Davis, CA 95616 USA. [Ardlie, Kristin G.] SeraCare Life Sci, Cambridge, MA 02139 USA. [Worthington, Jane] Univ Manchester, Arthrit Res Campaign Epidemiol Unit, Manchester M13 9PT, Lancs, England. [Seielstad, Mark] Genome Inst Singapore, Singapore 138672, Singapore. RP Plenge, RM (reprint author), Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM rplenge@partners.org RI Padyukov, Leonid/A-4890-2009; Altshuler, David/A-4476-2009; de Vries, Niek/J-9348-2013; Worthington, Jane/M-9770-2014; OI Padyukov, Leonid/0000-0003-2950-5670; Altshuler, David/0000-0002-7250-4107; de Vries, Niek/0000-0002-6257-8604; Worthington, Jane/0000-0003-0544-042X; Seielstad, Mark/0000-0001-5783-1401; Alfredsson, Lars/0000-0003-1688-6697; Klareskog, Lars/0000-0001-9601-6186 FU T32 NIH training grant [AR007530-23]; NIH [KAR055688A, AI55314-3, RO1-AR44422, NO1-AR-2-2263, R01 AR49880, CA87969, P60 AR047782, K24 AR0524-01, BIRCWH K12 HD051959]; Fox Trot Fund; William Randolph Hearst Fund of Harvard University; Burroughs Wellcome Fund; UO1 NIH [UO1 HG004171]; Millennium Pharmaceuticals and Biogen-Idec; National Center for Research Resources [U54 RR020278]; National Institutes of Health; Swedish Medical Research Council; Swedish Council for Working Life and Social Research; King Gustaf V's 80-year Foundation; Swedish Rheumatic Foundation; Stockholm County Council; Arbetsmarknadens Forrsarkringsaktiebolag; lCounty of Sormland Research and Development Center; Agency for Science Technology and Research (Singapore); Doris Duke Charitable Foundation; US National Institute of Mental Health; National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development; American College of Rheumatology Arthritis Investigator Award; Katherine Swan Ginsburg Memorial Award; Kirkland Scholar Awardee [K24 AR02175, R01 AI065841, 5 M01 RR-00079]; European Community's FP6 funding FX We thank the WTCCC for making access to genotype data available online, and for providing autoantibody status of the WTCCC rheumatoid arthritis cases. We thank S. Myers and J. Marchini for help with IMPUTE. S. R. is supported by a T32 NIH training grant (AR007530-23), a K08 grant from the NIH (KAR055688A), and through the BWH Rheumatology Fellowship program, directed by S. Helfgott. R. M. P. is supported by a K08 grant from the NIH (AI55314-3), a private donation from the Fox Trot Fund, the William Randolph Hearst Fund of Harvard University, and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. M. J. D. is supported by a UO1 NIH grant (UO1 HG004171). The BRASS Registry is supported by a grant from Millennium Pharmaceuticals and Biogen-Idec. The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research Resources. The NARAC is supported by NIH grants RO1-AR44422 and NO1-AR-2-2263 (P. K. G.). This work was also supported in part by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. The EIRA study is supported by grants from the Swedish Medical Research Council, the Swedish Council for Working Life and Social Research, King Gustaf V's 80-year Foundation, the Swedish Rheumatic Foundation, the Stockholm County Council, the insurance company Arbetsmarknadens Forrsarkringsaktiebolag, and the County of Sormland Research and Development Center. Genotyping of the EIRA cohort was supported by the Agency for Science Technology and Research (Singapore). Genotyping of the GCI and LUMC samples was funded by Celera. D. A. is a Burroughs Wellcome Fund Clinical Scholar in Translational Research, and a Distinguished Clinical Scholar of the Doris Duke Charitable Foundation. B. D. K. was supported by the NIH Clinical Research Training Program, a public-private partnership between the Foundation for the National Institutes of Health and Pfizer Inc. E. W. K. is supported by NIH grants R01 AR49880, CA87969, P60 AR047782, K24 AR0524-01 and BIRCWH K12 HD051959 (supported by US National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development and the Office of the Director). K. H. C. is the recipient of an Arthritis Foundation/American College of Rheumatology Arthritis Investigator Award and a Katherine Swan Ginsburg Memorial Award. L. A. C. is a Kirkland Scholar Awardee and her work on this project was supported by K24 AR02175, R01 AI065841 and 5 M01 RR-00079. P. P. T. and N. d. V. were supported by European Community's FP6 funding (Autocure). We acknowledge the help of C. Ellen van der Schoot for healthy control samples for GENRA and the help of B. A. C. Dijkmans, D. van Schaardenburg, A. S. Pena, P.L. Klarenbeek, Z. Zhang, M. T. Nurmohammed, W. F. Lems, R. R. J. van de Stadt, W. H. Bos, J. Ursum, M. G. M. Bartelds, D. M. Gerlag, M. G. H. van der Sande, C. A. Wijbrandts and M. M. J. Herenius in gathering GENRA subject samples and data. We thank Y. Li, S. Schrodi, and J. Sninsky (Celera); and B. Voight and C. Cotsapas (Broad Institute) for comments on the manuscript. NR 30 TC 337 Z9 342 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2008 VL 40 IS 10 BP 1216 EP 1223 DI 10.1038/ng.233 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 354PH UT WOS:000259651000022 PM 18794853 ER PT J AU Hartong, DT Dange, M Mcgee, TL Berson, EL Dryja, TP Colman, RF AF Hartong, Dyonne T. Dange, Mayura McGee, Terri L. Berson, Eliot L. Dryja, Thaddeus P. Colman, Roberta F. TI Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle SO NATURE GENETICS LA English DT Article ID RAT-LIVER MITOCHONDRIA; POSITIONAL CLONING; BETA-SUBUNIT; PIG-HEART; GENE; MUTATIONS; TRANSHYDROGENASE; IDENTIFICATION AB Here we describe two families with retinitis pigmentosa, a hereditary neurodegeneration of rod and cone photoreceptors in the retina. Affected family members were homozygous for loss-of-function mutations in IDH3B, encoding the beta-subunit of NAD-specific isocitrate dehydrogenase (NAD-IDH, or IDH3), which is believed to catalyze the oxidation of isocitrate to a-ketoglutarate in the citric acid cycle. Cells from affected individuals had a substantial reduction of NAD-IDH activity, with about a 300-fold increase in the Km for NAD. NADP-specific isocitrate dehydrogenase (NADP-IDH, or IDH2), an enzyme that catalyzes the same reaction, was normal in affected individuals, and they had no health problems associated with the enzyme deficiency except for retinitis pigmentosa. These findings support the hypothesis that mitochondrial NADP-IDH, rather than NAD-IDH, serves as the main catalyst for this reaction in the citric acid cycle outside the retina, and that the retina has a particular requirement for NAD-IDH. C1 [Hartong, Dyonne T.; McGee, Terri L.; Dryja, Thaddeus P.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. [Dange, Mayura; Colman, Roberta F.] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA. [Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Dryja, TP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. EM thaddeus.dryja@novartis.com FU NEI NIH HHS [NIH-EY00169, NIH-EY08683, P30 EY014104, P30-EY014104, R01 EY000169, R01 EY000169-36, R01 EY008683, R37 EY000169]; NHLBI NIH HHS [NIH-HL67774, R01 HL067774] NR 23 TC 62 Z9 65 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2008 VL 40 IS 10 BP 1230 EP 1234 DI 10.1038/ng.223 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 354PH UT WOS:000259651000024 PM 18806796 ER PT J AU Korn, JM Kuruvilla, FG McCarroll, SA Wysoker, A Nemesh, J Cawley, S Hubbell, E Veitch, J Collins, PJ Darvishi, K Lee, C Nizzari, MM Gabriel, SB Purcell, S Daly, MJ Altshuler, D AF Korn, Joshua M. Kuruvilla, Finny G. McCarroll, Steven A. Wysoker, Alec Nemesh, James Cawley, Simon Hubbell, Earl Veitch, Jim Collins, Patrick J. Darvishi, Katayoon Lee, Charles Nizzari, Marcia M. Gabriel, Stacey B. Purcell, Shaun Daly, Mark J. Altshuler, David TI Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs SO NATURE GENETICS LA English DT Article ID HUMAN GENOME; ALGORITHM; LIKELIHOOD; ACCURATE; ARRAYS AB Accurate and complete measurement of single nucleotide (SNP) and copy number (CNV) variants, both common and rare, will be required to understand the role of genetic variation in disease. We present Birdsuite, a four-stage analytical framework instantiated in software for deriving integrated and mutually consistent copy number and SNP genotypes. The method sequentially assigns copy number across regions of common copy number polymorphisms (CNPs), calls genotypes of SNPs, identifies rare CNVs via a hidden Markov model (HMM), and generates an integrated sequence and copy number genotype at every locus (for example, including genotypes such as A-null, AAB and BBB in addition to AA, AB and BB calls). Such genotypes more accurately depict the underlying sequence of each individual, reducing the rate of apparent mendelian inconsistencies. The Birdsuite software is applied here to data from the Affymetrix SNP 6.0 array. Additionally, we describe a method, implemented in PLINK, to utilize these combined SNP and CNV genotypes for association testing with a phenotype. C1 [Korn, Joshua M.; Kuruvilla, Finny G.; McCarroll, Steven A.; Wysoker, Alec; Nemesh, James; Nizzari, Marcia M.; Gabriel, Stacey B.; Purcell, Shaun; Daly, Mark J.; Altshuler, David] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. [Korn, Joshua M.; Kuruvilla, Finny G.; McCarroll, Steven A.; Wysoker, Alec; Nemesh, James; Nizzari, Marcia M.; Gabriel, Stacey B.; Purcell, Shaun; Daly, Mark J.; Altshuler, David] MIT, Cambridge, MA 02142 USA. [Korn, Joshua M.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Korn, Joshua M.] Harvard Univ, Grad Program Biophys, Cambridge, MA 02138 USA. [Korn, Joshua M.; Kuruvilla, Finny G.; McCarroll, Steven A.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Korn, Joshua M.; Kuruvilla, Finny G.; McCarroll, Steven A.; Purcell, Shaun; Daly, Mark J.; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kuruvilla, Finny G.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Cawley, Simon; Hubbell, Earl; Veitch, Jim; Collins, Patrick J.] Affymetrix Inc, Santa Clara, CA 95051 USA. [Darvishi, Katayoon; Lee, Charles] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Daly, Mark J.; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Korn, JM (reprint author), Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. EM jkorn@broad.mit.edu; altshuler@molbio.mgh.harvard.edu RI McCarroll, Steven/A-8433-2009; Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; McCarroll, Steven/0000-0002-6954-8184 FU Lilly Life Sciences Research Fellowship FX We wish to thank G. Getz for discussions on algorithms and comments regarding the supplemental methods. We also thank E. Lander and J. Hirschhorn for their readings and feedback. Finally, we are indebted to the testing labs that provided us with many replicates of HapMap samples run on the Affymetrix SNP 6.0 array. S. A. M. was supported by a Lilly Life Sciences Research Fellowship. NR 21 TC 461 Z9 472 U1 1 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2008 VL 40 IS 10 BP 1253 EP 1260 DI 10.1038/ng.237 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 354PH UT WOS:000259651000028 PM 18776909 ER PT J AU Heng, TSP Painter, MW AF Heng, Tracy S. P. Painter, Michio W. CA Immunological Genome Project TI The Immunological Genome Project: networks of gene expression in immune cells SO NATURE IMMUNOLOGY LA English DT Editorial Material ID DATABASE C1 [Heng, Tracy S. P.; Painter, Michio W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Sect Immunol & Immunogenet,Joslin Diabet Ctr, Boston, MA 02215 USA. [Heng, Tracy S. P.; Painter, Michio W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02215 USA. RP Heng, TSP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Sect Immunol & Immunogenet,Joslin Diabet Ctr, Boston, MA 02215 USA. RI Gray, Daniel/A-3293-2013 OI Gray, Daniel/0000-0002-8457-8242 FU NIAID NIH HHS [R24AI072073] NR 18 TC 373 Z9 373 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2008 VL 9 IS 10 BP 1091 EP 1094 DI 10.1038/ni1008-1091 PG 4 WC Immunology SC Immunology GA 349XC UT WOS:000259315600003 PM 18800157 ER PT J AU Sadelain, M Kwak, LW Haining, N AF Sadelain, Michel Kwak, Larry W. Haining, Nick TI Turning T cells against tumors SO NATURE MEDICINE LA English DT Editorial Material C1 [Sadelain, Michel] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kwak, Larry W.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Haining, Nick] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sadelain, M (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2008 VL 14 IS 10 BP 1022 EP 1022 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 358BU UT WOS:000259892300026 ER PT J AU Ruvkun, G AF Ruvkun, Gary TI The perfect storm of tiny RNAs SO NATURE MEDICINE LA English DT Editorial Material ID NEMATODE CAENORHABDITIS-ELEGANS; HETEROCHRONIC GENE LIN-14; C-ELEGANS; REGULATORY RNA; DEVELOPMENTAL SWITCH; MESSENGER-RNAS; CELL LINEAGES; INTERFERENCE; EXPRESSION; PROTEIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Fruit St, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu NR 47 TC 75 Z9 75 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2008 VL 14 IS 10 BP 1041 EP 1045 DI 10.1038/nm1008-1041 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 358BU UT WOS:000259892300032 PM 18841145 ER PT J AU Kakkar, R Lee, RT AF Kakkar, Rahul Lee, Richard T. TI The IL-33/ST2 pathway: therapeutic target and novel biomarker SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID INTERLEUKIN-1 RECEPTOR FAMILY; HUMAN ATHEROSCLEROTIC PLAQUES; SOLUBLE ST2 PROTEIN; E-DEFICIENT MICE; CELLS AGGRAVATES ATHEROSCLEROSIS; ELEVATION MYOCARDIAL-INFARCTION; ALLERGIC AIRWAY INFLAMMATION; ACUTE CORONARY SYNDROMES; LOW-DENSITY LIPOPROTEIN; TOLL-LIKE RECEPTORS AB For many years, the interleukin-1 receptor family member ST2 was an orphan receptor that was studied in the context of inflammatory and autoimmune disease. However, in 2005, a new cytokine-interleukin-33 (IL-33) - was identified as a functional ligand for ST2. IL-33/ST2 signalling is involved in T-cell mediated immune responses, but more recently, an unanticipated role in cardiovascular disease has been demonstrated. IL-33/ST2 not only represents a promising cardiovascular biomarker but also a novel mechanism of intramyocardial fibroblast-cardiomyocyte communication that may prove to be a therapeutic target for the prevention of heart failure. C1 [Kakkar, Rahul] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lee, Richard T.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Partners Res Facil, Cambridge, MA 02139 USA. RP Kakkar, R (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB-804,55 Fruit St, Boston, MA 02114 USA. EM rkakkar@partners.org; rlee@partners.org FU NHLBI NIH HHS [R01 HL092930] NR 172 TC 247 Z9 260 U1 2 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD OCT PY 2008 VL 7 IS 10 BP 827 EP 840 DI 10.1038/nrd2660 PG 14 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 355AM UT WOS:000259681000016 PM 18827826 ER PT J AU Kazantsev, AG Thompson, LM AF Kazantsev, Aleksey G. Thompson, Leslie M. TI Therapeutic application of histone deacetylase inhibitors for central nervous system disorders SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID RUBINSTEIN-TAYBI-SYNDROME; SPINAL MUSCULAR-ATROPHY; AMYOTROPHIC-LATERAL-SCLEROSIS; FRAGILE-X-SYNDROME; CHOLESTEROL-BIOSYNTHESIS PATHWAY; SUBEROYLANILIDE HYDROXAMIC ACID; PICK C1-DEFICIENT NEURONS; SMALL-MOLECULE ACTIVATORS; MEF2 TRANSCRIPTION FACTOR; CREB-BINDING PROTEIN AB Histone deacetylases (HDACs) - enzymes that affect the acetylation status of histones and other important cellular proteins - have been recognized as potentially useful therapeutic targets for a broad range of human disorders. Pharmacological manipulations using small-molecule HDAC inhibitors - which may restore transcriptional balance to neurons, modulate cytoskeletal function, affect immune responses and enhance protein degradation pathways - have been beneficial in various experimental models of brain diseases. Although mounting data predict a therapeutic benefit for HDAC-based therapy, drug discovery and development of clinical candidates face significant challenges. Here, we summarize the current state of development of HDAC therapeutics and their application for the treatment of human brain disorders such as Rubinstein - Taybi syndrome, Rett syndrome, Friedreich's ataxia, Huntington's disease and multiple sclerosis. C1 [Kazantsev, Aleksey G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Thompson, Leslie M.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA. [Thompson, Leslie M.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. [Thompson, Leslie M.] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. RP Kazantsev, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Neurodegenerat Dis, Bldg 114-3300,16th St, Charlestown, MA 02129 USA. EM akazantsev@partners.org NR 218 TC 420 Z9 429 U1 4 U2 43 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD OCT PY 2008 VL 7 IS 10 BP 854 EP 868 DI 10.1038/nrd2681 PG 15 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 355AM UT WOS:000259681000018 PM 18827828 ER PT J AU Bertram, L Tanzi, RE AF Bertram, Lars Tanzi, Rudolph E. TI Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID ANGIOTENSIN-CONVERTING ENZYME; AMYLOID PRECURSOR PROTEIN; NICOTINIC ACETYLCHOLINE-RECEPTORS; CYSTATIN-C GENE; WHOLE-GENOME ASSOCIATION; PUBLIC-HEALTH IMPACT; APOLIPOPROTEIN-E; INCREASED FREQUENCY; PARKINSONS-DISEASE; MISSENSE MUTATIONS AB The genetic underpinnings of Alzheimer's disease (AD) remain largely elusive despite early successes in identifying three genes that cause early-onset familial AD (those that encode amyloid precursor protein (APP) and the presenilins (PSEN1 and PSEN2)), and one genetic risk factor for late-onset AD (the gene that encodes apolipoprotein E (APOE)). A large number of studies that aimed to help uncover the remaining disease-related loci have been published in recent decades, collectively proposing or refuting the involvement of over 500 different gene candidates. Systematic meta-analyses of these studies currently highlight more than 20 loci that have modest but significant effects on AD risk. This Review discusses the putative pathogenetic roles and common biochemical pathways of some of the most genetically and biologically compelling of these potential AD risk factors. C1 [Bertram, Lars; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Genet & Aging Res Unit, MIND, Dept Neurol, Charlestown, MA 02129 USA. RP Bertram, L (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, MIND, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM bertram@helix.mgh.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU National Institute on Aging [5R01AG23667]; National Institute of Mental Health [5R37MH60009]; Cure Alzheimer's Fund FX This work was sponsored by grants from the National Institute on Aging (5R01AG23667 to L. B.) and the National Institute of Mental Health (5R37MH60009 to R.E.T.). The AlzGene database was developed in collaboration with the Alzheimer Research Forum and is funded by the Cure Alzheimer's Fund. NR 110 TC 393 Z9 402 U1 8 U2 80 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD OCT PY 2008 VL 9 IS 10 BP 768 EP 778 DI 10.1038/nrn2494 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 349ZW UT WOS:000259323200014 PM 18802446 ER PT J AU Azam, M Seeliger, MA Gray, NS Kuriyan, J Daley, GQ AF Azam, Mohammad Seeliger, Markus A. Gray, Nathanael S. Kuriyan, John Daley, George Q. TI Activation of tyrosine kinases by mutation of the gatekeeper threonine SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; GROWTH-FACTOR RECEPTOR; BCR-ABL; DRUG-RESISTANCE; PROTEIN-KINASES; LUNG-CANCER; INACTIVE-CONFORMATION; TRANSFORMING PROTEIN; CLINICAL RESISTANCE; DOMAIN MUTATIONS AB Protein kinases targeted by small-molecule inhibitors develop resistance through mutation of the 'gatekeeper' threonine residue of the active site. Here we show that the gatekeeper mutation in the cellular forms of c-ABL, c-SRC, platelet-derived growth factor receptor-alpha and -beta, and epidermal growth factor receptor activates the kinase and promotes malignant transformation of BaF3 cells. Structural analysis reveals that a network of hydrophobic interactions-the hydrophobic spine-characteristic of the active kinase conformation is stabilized by the gatekeeper substitution. Substitution of glycine for the residues constituting the spine disrupts the hydrophobic connectivity and inactivates the kinase. Furthermore, a small-molecule inhibitor that maximizes complementarity with the dismantled spine (compound 14) inhibits the gatekeeper mutation of BCR-ABL-T315I. These results demonstrate that mutation of the gatekeeper threonine is a common mechanism of activation for tyrosine kinases and provide structural insights to guide the development of next-generation inhibitors. C1 [Azam, Mohammad; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02215 USA. [Gray, Nathanael S.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Azam, Mohammad; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Seeliger, Markus A.; Kuriyan, John] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Seeliger, Markus A.; Kuriyan, John] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Chem, Berkeley, CA 94720 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02215 USA. [Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, Karp Res Bldg,7th Floor, Boston, MA 02215 USA. EM george.daley@childrens.harvard.edu RI Seeliger, Markus/D-6409-2013 FU US National Institutes of Health (NIH); NIH Roadmap for Medical Research; Leukemia and Lymphoma Society; Thomas Anthony Pappas Charitable Foundation; Burroughs Wellcome Fund; Life Science Research Foundation, Baltimore; NIH [K99GM08009] FX This study was supported by grants from the US National Institutes of Health (NIH), the NIH Director's Pioneer Award of the NIH Roadmap for Medical Research, the Leukemia and Lymphoma Society, and by private funds from the Thomas Anthony Pappas Charitable Foundation. G. Q. D. is a recipient of the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research. M. A. S. was supported by a Johnson & Johnson fellowship of the Life Science Research Foundation, Baltimore, and by NIH K99GM08009. NR 57 TC 207 Z9 207 U1 2 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD OCT PY 2008 VL 15 IS 10 BP 1109 EP 1118 DI 10.1038/nsmb.1486 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 356KL UT WOS:000259777000017 PM 18794843 ER PT J AU Perez, JM Grimm, J Josephson, L Weissleder, R AF Perez, J. Manuel Grimm, Jan Josephson, Lee Weissleder, Ralph TI Integrated nanosensors to determine levels and functional activity of human telomerase SO NEOPLASIA LA English DT Article ID HUMAN CANCER; IMMORTAL CELLS; PROTEIN; MELANOMA; DNA; RESPONSES; SUBSET; ASSAYS; HTERT; RNA AB Telomerase is a key oncogenic enzyme, and a number of novel telomerase inhibitors are currently under development. Because inhibition can be achieved either at the protein or at the enzymatic activity level, independent measurements of these parameters are important in the development of effective therapeutic agents. In the current study, we have developed a set of functional magnetic nanosensors capable of measuring the concentration of telomerase, as well as its enzymatic activity in parallel. The method is based on a magnetic relaxation switch assay, which can be performed in crude tissue samples and is fast and extremely sensitive. Using this method, we were able to detect different amounts of telomerase protein and activity in various cancer and normal cell lines. Furthermore, we were able to study the effect of phosphorylation on telomerase activity. This system not only could provide a rapid assay for the evaluation of antitelomerase therapies but could also be implemented to the study of other cancer markers. C1 [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu RI Grimm, Jan/B-1937-2008 FU National Institutes of Health [R24CA92782, R21/R33 CA91807, U54-CA119349, P50-CA86355, U54 CA126515, KO1 (CA101781), R25CA096945-05] FX This work was supported in part by the National Institutes of Health grants R24CA92782, R21/R33 CA91807, U54-CA119349, P50-CA86355, U54 CA126515 (R.W.), and KO1 (CA101781) to J.M.P. as well as R25CA096945-05 (J.G.). NR 34 TC 31 Z9 32 U1 0 U2 13 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD OCT PY 2008 VL 10 IS 10 BP 1066 EP 1072 DI 10.1593/neo.08350 PG 7 WC Oncology SC Oncology GA 348AY UT WOS:000259184400005 PM 18813356 ER PT J AU Wetmore, JB Lovett, DH Hung, AM Cook-Wiens, G Mahnken, JD Sen, S Johansen, KL AF Wetmore, James B. Lovett, David H. Hung, Adriana M. Cook-Wiens, Galen Mahnken, Jonathan D. Sen, Saunak Johansen, Kirsten L. TI Associations of interleukin-6, C-reactive protein and serum amyloid A with mortality in haemodialysis patients SO NEPHROLOGY LA English DT Article DE albumin; CRP; dialysis; IL-6; mortality; serum amyloid A ID CHRONIC-RENAL-FAILURE; APPARENTLY HEALTHY-MEN; CARDIOVASCULAR MORTALITY; DIALYSIS PATIENTS; ALBUMIN CONCENTRATION; GENE-EXPRESSION; BLOOD-PRESSURE; ALL-CAUSE; FETUIN-A; INFLAMMATION AB Background: Individuals with end-stage renal disease (ESRD) manifest a chronic inflammatory state. Serum albumin, C-reactive protein (CRIP), interleukin-6 (IL-6) and serum amyloid A (SAA) have been associated with mortality in ESRD, although reports vary as to whether they are true independent markers of mortality. We undertook a prospective study to determine whether these markers could predict mortality in ESRD. Methods: A cohort of individuals on haemodialysis was followed prospectively for a mean of 2.1 years. Albumin, CRR IL-6 and SAA were drawn at enrolment. Association between mortality and serum markers was assessed using Cox proportional hazards regression. A trend analysis was undertaken to establish the functional form of the association between serum markers and outcome. Results: After multivariable adjustment, IL-6 was most strongly associated with mortality, followed Closely by albumin (P = 0.0002 and P = 0.0005, respectively). CRP was marginally associated with mortality (P = 0.046), and SAA was not independently associated with mortality. In the final model adjusting for the effects of both IL-6 and albumin simultaneously, both markers remained associated with mortality (P = 0.003 and P = 0.011). Conclusion: IL-6 had the strongest independent association with mortality, followed closely by albumin. CRP and SAA were not associated with mortality when measured at single time points. Increasing levels of IL-6 and decreasing levels of albumin were associated with increased mortality. IL-6 and albumin may be capturing different aspects of the inflammatory burden observed in haemodialysis patients. C1 [Wetmore, James B.; Lovett, David H.; Hung, Adriana M.; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco VAMC, San Francisco, CA USA. [Cook-Wiens, Galen; Mahnken, Jonathan D.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Mahnken, Jonathan D.] Univ Kansas, Sch Med, Ctr Biostat & Adv Informat, Kansas City, KS USA. [Sen, Saunak] Univ Kansas, Sch Med, Dept Biostat, Kansas City, KS USA. RP Wetmore, JB (reprint author), MS 3002,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM jwetmore@kumc.edu FU NIH [DK 39776, DK 56182, DK 07219]; UCSF Foundation Greenberg Awards [80357, 60519]; Amgen [20010180]; National Kidney Foundation FX This Study was supported by NIH grants DK 39776 (DHL), DK 56182 (KLJ), DK 07219 (JBW), UCSF Foundation Greenberg Awards #80357 and #60519 (DHL, KLJ), Amgen Grant. #20010180 (AMH, DHL, KLJ) mid National Kidney Foundation Fellow Grants (AMH, JBW). We thank Satellite Dialysis for assistance in patient recruitment. NR 55 TC 15 Z9 15 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD OCT PY 2008 VL 13 IS 7 BP 593 EP 600 DI 10.1111/j.1440-1797.2008.01021.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 361PJ UT WOS:000260139300007 PM 18826487 ER PT J AU Rajaraman, P Hutchinson, A Rothman, N Black, PM Fine, HA Loeffler, JS Selker, RG Shapiro, WR Linet, MS Inskip, PD AF Rajaraman, Preetha Hutchinson, Amy Rothman, Nathaniel Black, Peter M. Fine, Howard A. Loeffler, Jay S. Selker, Robert G. Shapiro, William R. Linet, Martha S. Inskip, Peter D. TI Oxidative response gene polymorphisms and risk of adult brain tumors SO NEURO-ONCOLOGY LA English DT Article DE acoustic neuroma; brain; case-control; glioma; meningioma; neoplasm; oxidative response; polymorphism; tumor ID MANGANESE SUPEROXIDE-DISMUTASE; BREAST-CANCER RISK; PROSTATE-CANCER; GLUTATHIONE-PEROXIDASE; ANTIOXIDANT ENZYMES; OVARIAN-CANCER; STRESS GENES; MNSOD; CATALASE; ASSOCIATIONS AB Oxidative stress is believed to play a key role in tumor formation. Although this mechanism could be especially pertinent for brain tumors given the high oxygen consumption of the brain, very little has been published regarding brain tumor risk with respect to genes mediating oxidative stress. Using data from non-Hispanic whites in a hospital-based case-control study conducted by the National Cancer Institute between 1994 and 1998, we evaluated risk of glioma (n = 362), meningioma (n = 134), and acoustic neuroma (n = 69) compared to noncancer controls (n = 494) with respect to nine single nucleotide polymorphisms from seven genes involved in oxidative stress response (CAT, GPX1, NOS3, PON1, SOD1, SOD2, and SOD3). We observed increased risk of glioma (odds ratio [OR](CT/CC) = 1.3; 95% confidence interval [95% CI], 1.0-1.7) and meningioma (OR(CT/CC) = 1.7; 95% CI, 1.1-2.7) with the C variant of SOD3 rs699473. There was also indication of increased acoustic neuroma risk with the SOD2 rs4880 Ala variant (OR(CT/CC) = 2.0; 95% CI, 1.0-4.2) and decreased acoustic neuroma risk with the CAT rs1001179 T allele variant (OR(CT/TT) = 0.6; 95% CI, 0.3-1.0). These relationships persisted when major groups of disease controls were excluded from the analysis. Our results suggest that common variants in the SOD2, SOD3, and CAT genes may influence brain tumor risk. Neuro-Oncology 10, 709-715, 2008 (Posted to Neuro-Oncology [serial online], Doc. 08-00008, August 4, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-037) C1 [Rajaraman, Preetha; Rothman, Nathaniel; Linet, Martha S.; Inskip, Peter D.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Fine, Howard A.] NCI, Neurooncol Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Hutchinson, Amy] NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, Adv Technol Program,SAIC Frederick Inc, Frederick, MD USA. [Black, Peter M.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Loeffler, Jay S.] Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Boston, MA USA. [Selker, Robert G.] Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. [Shapiro, William R.] St Josef Hosp & Med Ctr, Barrow Neurol Inst, Phoenix, AZ USA. RP Rajaraman, P (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS Room 7085, Bethesda, MD 20892 USA. EM rajarama@mail.nih.gov FU National Cancer Institute; National Institutes of Health [N01-CO-12400]; Department of Health and Human Services FX This research was supported by Intramural funds from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. This project has been funded in whole or in part with federal fund from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. 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 34 TC 48 Z9 49 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 709 EP 715 DI 10.1215/15228517-2008-037 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500007 PM 18682580 ER PT J AU Park, MJ Kassam, A Gardner, P Prevedello, DM Soeda, A Lieberman, F Rosenberg, A Park, DM AF Park, Myung-Jin Kassam, Amin Gardner, Paul Prevedello, Daniel M. Soeda, Akio Lieberman, Frank Rosenberg, Andrew Park, Deric M. TI PLATELET-DERIVED GROWTH FACTOR STIMULATES CHORDOMA GROWTH AND INVASION BY ACTIVATING THE PI3K/AKT/MTOR SIGNALING PATHWAY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Park, Myung-Jin; Kassam, Amin; Gardner, Paul; Prevedello, Daniel M.; Soeda, Akio; Lieberman, Frank; Park, Deric M.] Univ Pittsburgh, Pittsburgh, PA USA. [Rosenberg, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Park, Deric/C-5675-2013 NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 764 EP 764 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500029 ER PT J AU Stegh, A Kesari, S Mahoney, J Jenq, H Forloney, K Protopopov, A Louis, D Chin, L Depinho, R AF Stegh, Alexander Kesari, Santosh Mahoney, John Jenq, Harry Forloney, Kristin Protopopov, Alexei Louis, David Chin, Lynda Depinho, Ronald TI BCL2L12-MEDIATED INHIBITION OF EFFECTOR CASPASES 3 AND 7 VIA DISTINCT MECHANISMS IN GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Stegh, Alexander] Dana Farber Canc Inst, Boston, MA 02115 USA. [Louis, David] MGH, Pathol & Canc Ctr, Charlestown, MA USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 766 EP 766 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500038 ER PT J AU Mukasa, A Chin, L Cavenee, W Furnari, F AF Mukasa, Akitake Chin, Lynda Cavenee, Webster Furnari, Frank TI MUTANT EGFR SIGNALING IN GLIOBLASTOMA TUMOR MAINTENANCE AND EMERGENCE OF RECEPTOR-IN DEPENDENT, TUMOR GROWTH-PROMOTING MECHANISMS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Mukasa, Akitake; Cavenee, Webster; Furnari, Frank] Univ Calif San Diego, Ludwig Inst, La Jolla, CA 92093 USA. [Chin, Lynda] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 776 EP 776 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500077 ER PT J AU Grewal, J Kesari, S AF Grewal, Jai Kesari, Santosh TI LOSS OF ESTROGEN AND PROGESTERONE SURFACE RECEPTORS DURING TREATMENT OF LEPTOMENINGEAL METASTASIS FROM BREAST CANCER SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Grewal, Jai] Neurol Surg PC, Great Neck, NY USA. [Kesari, Santosh] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 777 EP 777 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500078 ER PT J AU Eichler, A Lamont, E AF Eichler, April Lamont, Elizabeth TI MEASURING OCCURENCE AND TIMING OF BRAIN METASTASES USING ADMINISTRATIVE ICD-9 CODES SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Eichler, April; Lamont, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 780 EP 780 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500091 ER PT J AU Chen, C Richard, K Kesari, S Kung, A D'Andrea, A AF Chen, Clark Richard, Kennedy Kesari, Santosh Kung, Andrew D'Andrea, Alan TI PROTEASOME INHIBITION IN HIGH-GRADE GLIOMA TREATMENT: A STRATEGY FOR SIMULTANEOUS TUMORICIDAL ACTIVITY, TEMOZOLOMIDE CHEMOSENSITIZATION, AND RADIATION SENSITIZATION SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Chen, Clark] Harvard Univ, Boston, MA 02115 USA. [Richard, Kennedy] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 783 EP 784 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500102 ER PT J AU Chakravartti, A Wang, M Mischel, P Robins, HI Guha, A Machray, M Curran, W Roach, M Mehta, M Dicker, A AF Chakravartti, A. Wang, M. Mischel, P. Robins, H. I. Guha, A. Machray, M. Curran, W. Roach, M. Mehta, M. Dicker, A. TI AN UPDATE ON CORRELATIVE MOLECULAR ENDPOINTS FROM RTOG 0211: PHASE I/II STUDY OF GEFITINIB plus RADIATION FOR NEWLY DIAGNOSED GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Chakravartti, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, M.] Amer Coll Radiol, Philadelphia, PA USA. [Mischel, P.] Univ Calif Los Angeles, Los Angeles, CA USA. [Robins, H. I.; Mehta, M.] Univ Wisconsin, Madison, WI USA. [Guha, A.] Univ Toronto, Toronto, ON, Canada. [Machray, M.; Dicker, A.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Roach, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 785 EP 785 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500106 ER PT J AU Holdhoff, M Supko, J Gallia, G Weingart, J Quinones-Hinojosa, A Olivi, A Grossman, S AF Holdhoff, Matthias Supko, Jeffrey Gallia, Gary Weingart, Jon Quinones-Hinojosa, Alfredo Olivi, Alessandro Grossman, Stuart TI INTRATUMORAL CONCENTRATION OF IMATINIB MESYLATE IN PATIENTS WITH HIGH-GRADE GLIOMA: PRELIMINARY RESULTS FROM STUDY J0623 SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Holdhoff, Matthias; Grossman, Stuart] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Supko, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 788 EP 788 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500117 ER PT J AU Plotkin, S Halpin, C Stemmer-Rachamimov, A Barker, F Sorensen, G Jain, R Di Tomaso, E AF Plotkin, Scott Halpin, Christopher Stemmer-Rachamimov, Anat Barker, Fred Sorensen, Gregory Jain, Rakesh Di Tomaso, Emmanuelle TI ACTIVITY OF BEVACIZUMAB AGAINST NF2-RELATED VESTIBULAR SCHWANNOMAS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Plotkin, Scott; Halpin, Christopher; Stemmer-Rachamimov, Anat; Barker, Fred; Sorensen, Gregory; Jain, Rakesh; Di Tomaso, Emmanuelle] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 796 EP 796 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500145 ER PT J AU Scott, B Quant, EK Mcnamara, MB Ryg, PA Batchelor, TT Wen, PY AF Scott, Brian Quant, Eudocia K. Mcnamara, Margaret B. Ryg, Peter A. Batchelor, Tracy T. Wen, Patrick Y. TI BEVACIZUMAB SALVAGE THERAPY FOLLOWING PROGRESSION IN HIGH-GRADE GLIOMA PATIENTS TREATED WITH VEGF RECEPTOR TYROSINE KINASE INHIBITORS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Scott, Brian; Quant, Eudocia K.] Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 820 EP 820 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500233 ER PT J AU Quant, E Norden, A Drappatz, J Muzikansky, A Doherty, L Lafrankie, D Ciampa, A Kesari, S Wen, P AF Quant, Eudocia Norden, Andrew Drappatz, Jan Muzikansky, Alona Doherty, Lisa Lafrankie, Debra Ciampa, Abigail Kesari, Santosh Wen, Patrick TI ROLE OF A SECOND CHEMOTHERAPY IN RECURRENT MALIGNANT GLIOMA IN PATIENTS WHO PROGRESS ON A BEVACIZUMAB-CONTAINING REGIMEN SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Quant, Eudocia; Doherty, Lisa] Massachusetts Gen Hosp, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 823 EP 823 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500243 ER PT J AU Wen, P Kuhn, J Chang, S Lamborn, K Robbins, H Cloughesy, T Lieberman, F Mehra, M Gilbert, M Cooper, J Drappatz, J Kesari, S Norden, A Groves, M Aldape, K Yung, WKA Dancey, J Prados, M AF Wen, Patrick Kuhn, John Chang, Susan Lamborn, Kathleen Robbins, Hi Cloughesy, Timothy Lieberman, Frank Mehra, Minesh Gilbert, Mark Cooper, Josh Drappatz, Jan Kesari, Santosh Norden, Andrew Groves, Morris Aldape, Kenneth Yung, W. K. Alfred Dancey, Janet Prados, Michael TI PHASE I/II STUDY OF ERLOTINIB AND TEMSIROLIMUS (CCI-779) FOR PATIENTS WITH RECURRENT MALIGNANT GLIOMAS (NABTC 04-02) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Wen, Patrick] Ctr Neurooncol, Boston, MA USA. [Kuhn, John] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Chang, Susan; Lamborn, Kathleen; Prados, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Robbins, Hi] Univ Wisconsin, Madison, WI 53706 USA. [Cloughesy, Timothy] Univ Calif Los Angeles, Los Angeles, CA USA. [Lieberman, Frank] Univ Pittsburgh, Pittsburgh, PA USA. [Mehra, Minesh] Univ Wisconsin, Madison, WI USA. [Drappatz, Jan] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Groves, Morris; Aldape, Kenneth; Yung, W. K. Alfred] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Dancey, Janet] NCI, Bethesda, MD 20892 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 824 EP 824 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500245 ER PT J AU Bouchard, D Elian, K Neale, A Rosenfeld, S Drappatz, J Groves, M Wen, P Bento, P Lawrener, B Castaigne, JP AF Bouchard, Danielle Elian, Kelly Neale, Ann Rosenfeld, Steven Drappatz, Jan Groves, Morris Wen, Patrick Bento, Paula Lawrener, Betty Castaigne, Jean-Paul TI ANG1005, THE FIRST CLINICAL TRIAL IN PATIENTS WITH MALIGNANT GLIOMA: PRELIMINARY SAFETY AND TOLERABILITY DATA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Bouchard, Danielle; Elian, Kelly; Bento, Paula; Lawrener, Betty; Castaigne, Jean-Paul] Angiochem Inc, Montreal, PQ, Canada. [Neale, Ann] WinPharm Associated LLC, Danville, CA USA. [Drappatz, Jan] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Groves, Morris] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 828 EP 828 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500261 ER PT J AU Noda, S Palanichamy, K Modelska, A Chakravarti, A AF Noda, Shinei Palanichamy, Kamalakannan Modelska, Angelika Chakravarti, Arnab TI GRP78 IS A NOVEL TARGET FOR RADIATION THERAPY IN MALIGNANT GLIOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Noda, Shinei; Palanichamy, Kamalakannan; Modelska, Angelika] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Palanichamy, Kamalakannan/E-3807-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 852 EP 852 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500346 ER PT J AU Lucas, M Leahy, N AF Lucas, Michele Leahy, Noreen TI THE IMPACT OF DIAGNOSIS AND TREATMENT ON THE HIGH-GRADE BRAIN TUMOR FAMILY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Lucas, Michele; Leahy, Noreen] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 880 EP 880 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500446 ER PT J AU Fulci, G AF Fulci, Giulia TI MAGNETIC RESONANCE IMAGING OF INTRATUMORAL INFLAMMATION DURING ONCOLYTIC VIROTHERAPY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Fulci, Giulia] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 892 EP 892 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500488 ER PT J AU Gerstner, E Chen, PJ Batchelor, T Sorensen, AG AF Gerstner, Elizabeth Chen, Poe-Jou Batchelor, Tracy Sorensen, A. Gregory TI ROLE OF DIFFUSION MRI IN THE DETECTION OF INFILTRATIVE GLIOBLASTOMA AFTER TREATMENT WITH CEDIRANIB SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Gerstner, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 894 EP 894 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500495 ER PT J AU Hingtgen, S Kasmieh, R Figueiredo, JL Weissleder, R Shah, K AF Hingtgen, Shawn Kasmieh, Randa Figueiredo, Jose-Luiz Weissleder, Ralph Shah, Khalid TI FATE AND THERAPEUTIC EFFICACY OF NEURAL STEM CELLS IN MOUSE MODEL OF GLIOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Neuro-Oncology (SNO) CY NOV 20-23, 2008 CL Las Vegas, NV SP Soc Neuro Oncol C1 [Hingtgen, Shawn; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2008 VL 10 IS 5 BP 904 EP 904 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 357NX UT WOS:000259854500530 ER PT J AU Goldstein, JN Rosand, J Schwamm, LH AF Goldstein, Joshua N. Rosand, Jonathan Schwamm, Lee H. TI Warfarin reversal in anticoagulant-associated intracerebral hemorrhage SO NEUROCRITICAL CARE LA English DT Article DE cerebral hemorrhage; warfarin; plasma; blood coagulation factors; factor VII ID FRESH-FROZEN PLASMA; PROTHROMBIN COMPLEX CONCENTRATE; ACTIVATED FACTOR-VII; INTRAVENOUS PHYTONADIONE VITAMIN-K-1; INTERNATIONAL NORMALIZED RATIO; RECOMBINANT FACTOR VIIA; CENTRAL-NERVOUS-SYSTEM; FACTOR-IX COMPLEX; INTRACRANIAL HEMORRHAGE; ORAL ANTICOAGULATION AB Anticoagulant-associated intracerebral hemorrhage (ICH) is a devastating disease, causing death in half of patients and permanent disability in the majority of survivors. The finding that patients often continue bleeding after hospital presentation offers the possibility that emergency warfarin reversal may improve outcomes. As no clinical trials have demonstrated the superiority of any one treatment strategy, various treatment options are available. Intravenous vitamin K is the definitive therapy; however, as monotherapy it can require many hours to take effect. Therefore, it is often considered an adjunct agent. Coagulation factors can be repleted with fresh frozen plasma (FFP), which is widely available and relatively low cost, but can require substantial time to deliver in real-world settings. A number of coagulation factor products collectively termed prothrombin complex concentrates (PCCs) are widely available that can rapidly provide many or all the vitamin K-dependent coagulation factors. Recombinant activated factor VII is used in many centers for this purpose, as it is thought to provide a procoagulant effect that may compensate for the lack of the other critical factors. Until clinical trials demonstrate the superiority of any one means of warfarin reversal, a number of expert guidelines from national organizations are available to help local providers guide therapy. At our institution, we have focused on improving the rapid and reliable delivery of a combination of intravenous vitamin K and FFP, with continued re-dosing until the desired INR lowering is achieved. C1 [Rosand, Jonathan; Schwamm, Lee H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Goldstein, Joshua N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Schwamm, LH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, ACC 720,55 Fruit St, Boston, MA 02114 USA. EM lschwamm@partners.org RI Goldstein, Joshua/H-8953-2016; OI Schwamm, Lee/0000-0003-0592-9145 FU Miles and Eleanor Shore 50th Anniversary Fellowship Award; National Institute of Neurological Disorders and Stroke [NIH 1 K23 NS42695, R01 NS04217]; Jerome Lyle Rappaport Charitable Foundation FX We thank Dr. Walter (Sunny) Dzik for helpful discussion and commentary. Grant support: Funding from the Miles and Eleanor Shore 50th Anniversary Fellowship Award, the National Institute of Neurological Disorders and Stroke (NIH 1 K23 NS42695, R01 NS04217), and the Jerome Lyle Rappaport Charitable Foundation. NR 86 TC 36 Z9 39 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD OCT PY 2008 VL 9 IS 2 BP 277 EP 283 DI 10.1007/s12028-008-9049-z PG 7 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 351RC UT WOS:000259441300019 PM 18214714 ER PT J AU Witzel, T Lin, FH Rosen, BR Wald, LL AF Witzel, Thomas Lin, Fa-Hsuan Rosen, Bruce R. Wald, Lawrence L. TI Stimulus-induced Rotary Saturation (SIRS): A potential method for the detection of neuronal currents with MRI SO NEUROIMAGE LA English DT Article DE fMRI; neuronal current imaging; rotary saturation; T1rho ID MICROTESLA MAGNETIC-FIELDS; PULSE SEQUENCE; HUMAN BRAIN; RESONANCE; MAGNETOENCEPHALOGRAPHY; OPTIMIZATION; OSCILLATIONS; STIMULATION; SENSITIVITY; RESPONSES AB Neuronal currents produce local transient and oscillatory magnetic fields that can be readily detected by MEG. Previous work attempting to detect these magnetic fields with MR focused on detecting local phase shifts and dephasing in T-2 or T-2*-weighted images. For temporally biphasic and multi-phasic local currents the sensitivity of these methods can be reduced through the cancellation of the accrued phase induced by positive and negative episodes of the neuronal current. The magnitude of the phase shift is also dependent on the distribution of the current within the voxel. Since spins on one side of a current Source develop an opposite phase shift relative to those on the other side, there is likely to be significant cancellation within the voxel. We introduce a potential method for detecting neuronal currents though their resonant T-1 rho saturation during a spin-lock preparation period. The method is insensitive to the temporal and spatial cancellation effects since it utilizes the multi-phasic nature of the neuronal currents and thus is not sensitive to the sign of the local field. To produce a T-1 rho reduction, the Larmor frequency in the rotating frame, which is set by gamma B-1lock (typically 20 Hz-5 kHz), must match the major frequency components of the stimulus-indUced neuronal currents. We validate the method in MRI phantom studies. The rotary saturation spectra showed a sharp resonance when a current dipole within the phantom was driven at the Larmor frequency in the rotating frame. A 7 min block-design experiment was found to be sensitive to a current dipole strength of 56 nAm, an approximate magnetic field of 1 nT at 1.5 mm from the dipole. This dipole moment is similar to that seen using the phase shift method in a similar experimental setup by Konn et al. [Konn, D.,Gowland, P., Bowtell, R.,2003. MRI detection of weak magnetic fields due to an extended current dipole in a conducting sphere: a model for direct detection of neuronal currents in the brain. Magn. Reson. Med. 50, 40-49], but is potentially less encumbered by temporal and spatial cancellation effects. Published by Elsevier Inc. C1 [Witzel, Thomas; Rosen, Bruce R.] Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Witzel, Thomas; Lin, Fa-Hsuan; Rosen, Bruce R.; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. RP Witzel, T (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr, Bldg 149,13th St,Rm 2301, Charlestown, MA 02129 USA. EM twitzel@nmr.mgh.harvard.edu RI Lin, Fa-Hsuan/G-6988-2012; Witzel, Thomas/P-1402-2014; Wald, Lawrence/D-4151-2009 OI Lin, Fa-Hsuan/0000-0002-9539-1731; FU NIH/NIDCD [5T32DC000038-15]; NCRR [P41RR14075]; NIH [1R21EB007298]; NSC [96-2320-B-002-085, NHRI-EX97-9715EC]; MIND Institute FX We would like to acknowledge Dr. Joseph Mandeville and Dr. Jonathan Polimeni for the stimulating discussions and helpful assistance with the implementation of the experiment. This project was financially supported by NIH/NIDCD 5T32DC000038-15, NCRR P41RR14075, NIH 1R21EB007298, NSC 96-2320-B-002-085, NHRI-EX97-9715EC and the MIND Institute. NR 34 TC 20 Z9 20 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2008 VL 42 IS 4 BP 1357 EP 1365 DI 10.1016/j.neuroimage.2008.05.010 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 351CB UT WOS:000259401000010 PM 18684643 ER PT J AU Ganis, G Schendan, HE AF Ganis, Giorgio Schendan, Haline E. TI Visual mental imagery and perception produce opposite adaptation effects on early brain potentials SO NEUROIMAGE LA English DT Article ID EVENT-RELATED POTENTIALS; OBJECT-RECOGNITION AREAS; NEUROPHYSIOLOGICAL EVIDENCE; FACE PERCEPTION; SPATIOTEMPORAL DYNAMICS; SELECTIVE ATTENTION; PREFRONTAL CORTEX; CLOSURE PROCESSES; UNFAMILIAR FACES; FAMOUS FACES AB Event-related potentials (ERPs) were recorded during a rapid adaptation paradigm to determine whether visual perception and visual mental imagery of faces recruit the same early perceptual processes. The early effect of face and object adaptors, either perceived or visualized, on test stimuli, was assessed by measuring the amplitude of the N170/VPP complex, typically much larger for faces than for other object categories. Faces elicited a robust N170/VPP complex, localized to posterior ventrolateral occipitotemporal Cortex. Both Visualized and perceived adaptors affected the N170/VPP complex to test faces from 120 ms post-stimulus, reflecting effects oil neural populations supporting early perceptual face categorization. Critically, while perceived adaptors suppressed the amplitude of the N170/VPP, visualized adaptors enhanced it. We suggest that perceived adaptors affect neural populations in the neocortex supporting early perceptual processing of faces via bottom-up mechanisms, whereas visualized adaptors affect them via top-down mechanisms. Similar enhancement effects were found on the N170/VPP complex to non-face objects, suggesting Such effects are a general consequence of visual imagery oil processing of faces and other object categories. These findings Support image-percept equivalence theories and may explain, in part, why Visual percepts and Visual mental images are not routinely confused, even though both engage similar neural populations in the visual system. (C) 2008 Elsevier Inc. All rights reserved. C1 [Ganis, Giorgio] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Ganis, Giorgio] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ganis, Giorgio] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Schendan, Haline E.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP Ganis, G (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM ganis@nmr.mgh.harvard.edu OI Ganis, Giorgio/0000-0001-6175-2618; Schendan, Haline/0000-0001-8925-5605 FU Tufts University Faculty start-up funds; Faculty Research Award Committee (FRAC) FX Authors listed in alphabetical order, and contributed equally to all phases of this project. Research was supported by Tufts University Faculty start-up funds to H.E.S who was also supported by a Faculty Research Award Committee (FRAC) Research Semester Fellowship from Tufts University. Data acquisition was conducted in the Vision and Memory Neuroimaging Lab in the Department of Psychology at Tufts University. We would like to thank Stephen M. Maher, Lisa C. Lucia, and Roderick Elias for their technical assistance with data acquisition. NR 80 TC 35 Z9 36 U1 8 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2008 VL 42 IS 4 BP 1714 EP 1727 DI 10.1016/j.neuroimage.2008.07.004 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 351CB UT WOS:000259401000043 PM 18674625 ER PT J AU Liu, PK Mandeville, JB Dai, G Jenkins, BG Kim, YR Liu, CH AF Liu, Philip K. Mandeville, Joseph B. Dai, Guangping Jenkins, Bruce G. Kim, Young R. Liu, Christina H. TI Transcription MRI: A New View of the Living Brain SO NEUROSCIENTIST LA English DT Article DE Drug abuse; Molecular genetics; Immediate early gene; Transcription MRI ID FOCAL CEREBRAL-ISCHEMIA; FOS MESSENGER-RNA; IN-VIVO; C-FOS; GENE-EXPRESSION; CONTRAST AGENT; DELTA-FOSB; ANTISENSE OLIGODEOXYNUCLEOTIDE; CHRONIC COCAINE; CELLULAR UPTAKE AB Altered gene activities are underlying causes of many neurological disorders. The ability to detect, image, and report endogenous gene transcription using magnetic resonance (MR) holds great potential for providing significant clinical benefits. In this review, we present the development of conjugates consisting of gene-targeting short nucleic acids (oligodeoxynucleotides, or sODN) and superparamagnetic iron oxide nanoparticles (SPION, an MR susceptibility T-2 agent) for reporting gene activity using transcription MRI (tMRI). We will discuss 1) the target specificity of sODN, 2) selection of contrast agents for tMRI, 3) the distribution and uptake, 4) sequence specificity, 5) histology of SPION and sODN, 6) data acquisition and quantitative analysis for tMRI, and 7) application of gene transcript-targeting nanoparticles in biology and medicine. We will also discuss methods of validating the correlation between results from conventional assays (in situ hybridization, PCR, histology Prussian blue stain and immunohistochemistry) in postmortem samples and retention of SPION-sODN using tMRI. The application of our novel contrast probe to report and target gene transcripts in the mesolimbic pathways of living mouse brains after amphetamine exposure will be discussed. Because of the targeting ability in the nucleic acid sequence, the concept of tMRI probes with complementary nucleic acid (antisense DNA or short interfering RNA) allows not only tracking, targeting, binding to intracellular mRNA, and manipulating gene action but also tracing cells with specific gene action in living brains. Transcription MRI will lend itself to myriad applications in living organs. NEUROSCIENTIST 14(5):503-520, 2008. DOI: 10.1177/1073858407309746 C1 [Liu, Philip K.] Massachusetts Gen Hosp, Transcript Targeting & NeuroRepair Lab, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Liu, PK (reprint author), Massachusetts Gen Hosp, Transcript Targeting & NeuroRepair Lab, Dept Radiol, AA Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM philipl@nmr.mgh.harvard.edu OI Liu, Christina/0000-0002-5723-177X FU National Institutes of Health [R01 NS045845, NS057556] FX The authors thank Drs. CM Liu, S Huang, and JQ Ren for excellent assistance, Dr. B. Rosen for generous Support and advice, and Ms. N Eusemann for excellent editing. This project was supported by grants from the National Institutes of Health (R01 NS045845 and NS057556 to PKL) and the Athinoula A. A. Martinos Center for Biomedical Imaging. NR 60 TC 5 Z9 5 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD OCT PY 2008 VL 14 IS 5 BP 503 EP 520 DI 10.1177/1073858407309746 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 357ZV UT WOS:000259886800019 PM 18024855 ER PT J AU Aggarwal, S Cudkowicz, M AF Aggarwal, Swati Cudkowicz, Merit TI ALS drug development: Reflections from the past and a way forward SO NEUROTHERAPEUTICS LA English DT Review DE amyotrophic lateral sclerosis; clinical trial; trial design; conduct; critical review ID AMYOTROPHIC-LATERAL-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; MOTOR-NEURON DISEASE; III RANDOMIZED-TRIAL; E EPSILON-4 ALLELE; CLINICAL-TRIAL; DOUBLE-BLIND; SUPEROXIDE-DISMUTASE; VITAMIN-E; NEURODEGENERATIVE DISEASE AB Tremendous advances in our understanding of pathogenesis of amyotrophic lateral sclerosis (ALS) have provided a rich pipeline of drugs for clinical trialists. At least 32 unique compounds have been tested. Nevertheless, riluzole is currently the only treatment that prolongs survival. We present a critical overview of past clinical trials, how therapies are selected for testing in people, challenges with ALS clinical trial design and conduct, and ways to best move forward. C1 [Aggarwal, Swati; Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Dept Neurol, Charlestown, MA 02129 USA. RP Aggarwal, S (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, Dept Neurol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM spaggarwal@partners.org NR 69 TC 50 Z9 50 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD OCT PY 2008 VL 5 IS 4 BP 516 EP 527 DI 10.1016/j.nurt.2008.08.002 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 355SE UT WOS:000259727800004 PM 19019302 ER PT J AU Lentz, MR Lee, V Westmoreland, SV Ratai, EM Halpern, EF Gonzalez, RG AF Lentz, Margaret R. Lee, Vallent Westmoreland, Susan V. Ratai, Eva-Maria Halpern, Elkan F. Gonzalez, R. Gilberto TI Factor analysis reveals differences in brain metabolism in macaques with SIV/AIDS and those with SIV-induced encephalitis SO NMR IN BIOMEDICINE LA English DT Article DE human immunodeficiency virus (HIV); simian immunodeficiency virus (SIV); MRS; N-acetylaspartate; creatine; encephalitis; frontal cortex; factor analysis ID MAGNETIC-RESONANCE-SPECTROSCOPY; AIDS DEMENTIA COMPLEX; CENTRAL-NERVOUS-SYSTEM; HUMAN-IMMUNODEFICIENCY-VIRUS; CHOLINE-CONTAINING COMPOUNDS; PROTON MR SPECTROSCOPY; ANTIRETROVIRAL TREATMENT; NEUROLOGICAL DISEASES; N-ACETYLASPARTATE; NEURONAL INJURY AB MRS has often been used to study metabolic processes in the HIV-infected brain. However, it remains unclear how changes in individual metabolites are related to one another in this context of virus-induced central nervous system dysfunction. We used factor analysis (FA) to identify patterns of metabolite distributions from an MRS study of healthy macaques and those infected with simian immunodeficiency virus (SIV) which were moribund with AIDS. FA Summarized the correlations from nine metabolites into three main factors. Factor 3 identified patterns that discern healthy animals from those with SIV/AIDS. Factor 2 was able to differentiate between animals that had encephalitis and those moribund with AIDS but lacking encephalitis. Specifically Factor 2 was able to distinguish animals with moderate to severe encephalitis from animals with mild or no encephalitis as well as uninfected controls. FA not only confirmed the involvement of neuronal metabolites (N-acetylaspartate and glutamate) in disease severity, but also detected changes in creatine myo-inositol that have not been observed in the SIV macaque model previously. These results suggest that the divergent pathways of N-acetylaspartate and creatine in this disease may enable the commonly reported ratio N-acetylaspartate/creatnine to be a more sensitive marker of disease severity. Copyright (C) 2008 John Wiley & Sons. Ltd. C1 [Lentz, Margaret R.; Lee, Vallent; Ratai, Eva-Maria; Halpern, Elkan F.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Neuroradiol, Charlestown, MA 02129 USA. [Westmoreland, Susan V.] New England Reg Primate Res Ctr, Southborough, MA 01772 USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285,55 Fruit St, Boston, MA 02114 USA. EM rggonzalez@partners.org FU NCRR NIH HHS [RR000150, K26 RR000168, P41 RR014075, P41 RR14075, K01 RR000150, RR13213, P51 RR000168, RR00168-39]; NIBIB NIH HHS [EB002026, P41 EB002026]; NINDS NIH HHS [R01 NS034626, NS051129, K25 NS051129, R01 NS050041, NS050041, K25 NS051129-04, NS34626] NR 55 TC 11 Z9 11 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD OCT PY 2008 VL 21 IS 8 BP 878 EP 887 DI 10.1002/nbm.1276 PG 10 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 355RQ UT WOS:000259726400011 PM 18574793 ER PT J AU Voss, AC Maki, KC Garvey, WT Hustead, DS Alish, C Fix, B Mustad, VA AF Voss, Anne Coble Maki, Kevin C. Garvey, W. Timothy Hustead, Deborah S. Alish, Carolyn Fix, Brenda Mustad, Vikkie A. TI Effect of two carbohydrate-modified tube-feeding formulas on metabolic responses in patients with type 2 diabetes SO NUTRITION LA English DT Article DE type 2 diabetes; tube-feeding; slowly digested carbohydrate; monounsaturated fatty acids; glucose; insulin; glucagon-like peptide-1; fructo-oligosaccharides; omega-3 fatty acids; enteral formulas ID GLUCAGON-LIKE PEPTIDE-1; MONOUNSATURATED FATTY-ACIDS; GLYCEMIC INDEX; INSULIN-SECRETION; ENTERAL FORMULA; PLASMA-GLUCOSE; BLOOD-PRESSURE; MELLITUS; METAANALYSIS; HUMANS AB Objectives: This study evaluated the glycemic, insulinemic, and glucagon-like peptide-1 (GLP-1) responses of subjects with type 2 diabetes mellitus to consumption of two diabetes-specific tube-feeding formulas (slowly digested carbohydrate formula [SDC] and diabetes-specific formula [DSF]) and-one formula intended for individuals without diabetes (standard formula [STND]). Methods: Forty-eight subjects controlled with diet and/or oral anti hyperglycemic medications received the SDC, DSF, and STND. Postprandial glucose, insulin, and GLP-1 were measured on three occasions after an overnight fast in a double-blinded, randomized, three-treatment, crossover design. Results: The positive area under the curve for glucose and insulin with the STND was higher (P < 0.001) compared with the SDC and DSF. The adjusted GLP-1 concentration at 60 min was higher for the SDC compared with the DSF and STND (P < 0.05). Conclusion: Both lower-carbohydrate diabetes-specific formulas resulted in a lower postprandial blood glucose response compared with the STND. The formula also rich in slowly digested carbohydrate and monounsaturated and omega-3 fatty acids (SDC) produced significantly lower blood glucose and insulin responses and higher levels of GLP-1 in the presence of significantly lower insulin concentrations. These results support the view that the quantity and quality of carbohydrate and fat may play important roles in the management of patients with type 2 diabetes mellitus and could result in improved beta-cell function over the long term. (C) 2008 Elsevier Inc. All rights reserved. C1 [Voss, Anne Coble; Hustead, Deborah S.; Alish, Carolyn; Fix, Brenda; Mustad, Vikkie A.] Abbott Labs, Columbus, OH 43125 USA. [Maki, Kevin C.] Provident Clin Res, Glen Ellyn, IL USA. [Garvey, W. Timothy] Univ Alabama, Birmingham, AL USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. RP Voss, AC (reprint author), Abbott Labs, Columbus, OH 43125 USA. EM anne.voss@abbott.com NR 51 TC 14 Z9 15 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD OCT PY 2008 VL 24 IS 10 BP 990 EP 997 DI 10.1016/j.nut.2008.06.009 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 352ZF UT WOS:000259535200010 PM 18718737 ER PT J AU Meigs, JB Manning, AK Dupuis, J Liu, CY Florez, JC Cupples, LA AF Meigs, James B. Manning, Alisa K. Dupuis, Josee Liu, Chunyu Florez, Jose C. Cupples, L. Adrienne TI Ordered stratification to reduce heterogeneity in linkage to diabetes-related quantitative traits SO OBESITY LA English DT Article ID BODY-MASS INDEX; INSULIN-RESISTANCE ATHEROSCLEROSIS; GENOME-WIDE ASSOCIATION; BETA-CELL FUNCTION; INDEPENDENT REPLICATION; SUSCEPTIBILITY LOCUS; GLUCOSE-TOLERANCE; GENETIC-ANALYSIS; HERITAGE FAMILY; FASTING INSULIN AB Phenotypic heterogeneity complicates detection of genomic loci predisposing to type 2 diabetes, potentially obscuring or unmasking specific loci. We conducted ordered-subsets linkage analyses (OSAs) for diabetes-related quantitative traits (fasting insulin and glucose, hemoglobin A1c (HbA1c), and 28-year-time-averaged fasting plasma glucose (FPG)) from 330 families of the Framingham Offspring Study. We calculated mean BMI, waist circumference (WC), and a diabetes "age-of-onset score" for each family. We constructed subsets by adding one family at a time in increasing (lean family to obese) or decreasing (obese to lean) adiposity order, or increasing or decreasing propensity to develop diabetes at a younger age, with the OSA LOD reported as the maximum LOD observed in any subset. Permutation P values tested the hypothesis that phenotypic ordering showed stronger linkage than random ordering. On chromosome 1, ordering by increasing family mean WC increased linkage to time-averaged FPG at 256 cM from LOD = 2.4 to 3.5 (permuted P = 0.02) and to HbA1c at 180 cM from LOD = 2.0 to 3.3 (P = 0.01). On chromosome 19, ordering by decreasing WC increased linkage to fasting insulin at 68 cM from LOD = 2.7 to 4.6 (P = 0.002), and ordering by decreasing propensity to develop diabetes at a young age increased linkage to fasting insulin at 73 cM from LOD = 2.7 to 4.0 (P = 0.046). We conclude that chromosomes 1 and 19 could harbor adiposity-interacting diabetes susceptibility genes. Such interactions might also influence trait-locus associations and may be useful to consider in diabetes genome-wide association studies. C1 [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Boston, MA USA. [Manning, Alisa K.; Dupuis, Josee; Liu, Chunyu; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] MIT, Cambridge, MA 02139 USA. [Florez, Jose C.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. EM jmeigs@partners.org OI Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603 FU National Institutes of Health [R21 DK65732]; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; American Diabetes Association Career Development Award; GlaxoSmithKline; Sanofi-aventis FX This work was supported by National Institutes of Health R21 DK65732, the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), and by an American Diabetes Association Career Development Award to J.B.M. J.B.M. currently has research grants from GlaxoSmithKline and Sanofi-aventis and has received consulting fees from Interleukin Genetics, Kalypsis, and Outcomes. NR 45 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2008 VL 16 IS 10 BP 2314 EP 2322 DI 10.1038/oby.2008.354 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 354OR UT WOS:000259649400019 PM 18719643 ER PT J AU Ausk, KJ Ioannou, GN AF Ausk, Karlee J. Ioannou, George N. TI Is obesity associated with anemia of chronic disease? A population-based study SO OBESITY LA English DT Article ID C-REACTIVE PROTEIN; ADIPOSE-TISSUE; INSULIN-RESISTANCE; IRON-DEFICIENCY; SIGNALING ROLE; UNITED-STATES; INFLAMMATION; HEPCIDIN; PREVALENCE; ADULTS AB Obesity is characterized by chronic, low-grade, systemic inflammation, which, in turn, has been associated with anemia of chronic disease. We hypothesized that obesity may be associated with the features of anemia of chronic disease, including low hemoglobin concentration, low serum iron and transferrin saturation (TS), and elevated serum ferritin. We compared normal-weight to overweight and obese adult participants of the third National Health and Nutrition Examination Survey with respect to hemoglobin concentration and levels of serum iron, TS, and ferritin. Measured BMI was used to categorize participants into normal weight (BMI < 25 kg/m(2), n = 6,059), overweight (BMI 25 to < 30 kg/m(2), n = 5,108), mildly obese (BMI 30 to < 35 kg/m(2), n = 2,366), moderately obese (BMI 35 to < 40 kg/m(2), n = 850), and severely obese (BMI >= 40 kg/m(2), n = 465). After adjustment for age, gender, menstruation, race/ethnicity, education, alcohol consumption, smoking, blood donation, and dietary iron intake, serum ferritin was progressively higher with increasing BMI category, whereas serum iron and TS were progressively lower. However, compared to normal-weight persons, those in all other higher BMI categories did not have a significant change in hemoglobin concentration after adjustment for the above-mentioned confounders. Overweight and obesity were associated with changes in serum iron, TS, and ferritin that would be expected to occur in the setting of chronic, systemic inflammation. However, overweight and obese persons were not more likely to be anemic compared with normal-weight persons. C1 [Ausk, Karlee J.; Ioannou, George N.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Ioannou, George N.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA. RP Ioannou, GN (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM georgie@medicine.washington.edu FU American Liver Foundation and American Association for the Study of Liver Diseases Jan Albrecht Award; Research Enhancement Award Program, Veterans Affairs Puget Sound Health Care System FX This work was supported by the American Liver Foundation and American Association for the Study of Liver Diseases Jan Albrecht Award (G.N.I.), Research Enhancement Award Program, Veterans Affairs Puget Sound Health Care System (G.N.I.). NR 27 TC 63 Z9 66 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2008 VL 16 IS 10 BP 2356 EP 2361 DI 10.1038/oby.2008.353 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 354OR UT WOS:000259649400025 PM 18719644 ER PT J AU Ford, AA Wylie, BJ Waksmonski, CA Simpson, LL AF Ford, Abigail A. Wylie, Blair J. Waksmonski, Carol A. Simpson, Lynn L. TI Maternal congenital cardiac disease - Outcomes of pregnancy in a single tertiary care center SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 56th Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists CY MAY 03-07, 2008 CL New Orleans, LA SP Amer Coll Obstetricians & Gynecologists ID HEART-DISEASE; PROSPECTIVE MULTICENTER; WOMEN; COMPLICATIONS AB OBJECTIVE: To evaluate contemporary perinatal and cardiac outcomes of pregnancies in women with major structural congenital heart disease. METHODS: Obstetric, neonatal, and cardiac outcomes were abstracted retrospectively from medical records of all women with congenital cardiac disease delivering at our institution from 2000-2007 and compared by type of structural defect. Predictors of adverse cardiac or obstetric events were identified. RESULTS: Over the 7-year study period, 74 deliveries occurred in 69 women with congenital heart disease, median age 28 years. There were three right-obstructive defects, 14 left- obstructive defects, four right- regurgitant defects, 19 conotruncal defects, 19 shunts, and four miscellaneous lesions. There were 21 adverse cardiac events in 15 pregnancies (20.2%); these were defined as maternal death, congestive heart failure, myocardial infarction, stroke, the need for urgent cardiac intervention, or arrhythmia requiring treatment. There were 44 adverse obstetric events in 34 pregnancies (45.9%), defined as preterm delivery, stillbirth, preeclampsia, small for gestational age, or neonatal intensive care unit admission. Patients with shunt morphology were more likely to experience adverse obstetric and cardiac outcomes. CONCLUSION: Pregnancy in women with underlying major congenital heart defects poses increased risks to both mother and fetus. Nonetheless, favorable maternal and neonatal outcomes occur in the majority of patients. C1 [Ford, Abigail A.] Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY 10032 USA. Massachusetts Gen Hosp, Div Maternal Fetal Med, Boston, MA 02114 USA. Columbia Univ, Med Ctr, Div Cardiol, New York, NY 10032 USA. RP Ford, AA (reprint author), Columbia Univ, Med Ctr, Dept Obstet & Gynecol, 622 W 168th St PH 16-29, New York, NY 10032 USA. EM aaf2013@columbia.edu NR 18 TC 15 Z9 18 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2008 VL 112 IS 4 BP 828 EP 833 DI 10.1097/AOG.0b013e31818638c6 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 356GW UT WOS:000259767700013 PM 18827125 ER PT J AU Pfeiffer, E Vickers, SM Frank, E Grodzinsky, AJ Spector, M AF Pfeiffer, E. Vickers, S. M. Frank, E. Grodzinsky, A. J. Spector, M. TI The effects of glycosaminoglycan content on the compressive modulus of cartilage engineered in type II collagen scaffolds SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Cartilage; Tissue engineering; Mechanical properties; Modulus; Glycosaminoglycan; Scaffold; Collagen ID HUMAN ARTICULAR CHONDROCYTES; CHONDROGENESIS IN-VITRO; SKELETAL DEVELOPMENT; LIMB CHONDROGENESIS; GROWTH-FACTORS; CROSS-LINKING; CELL-CULTURE; TISSUE; MODULATION; MATRIX AB Objective: The current study determined the unconfined compressive modulus of tissue-engineered constructs with varying sulfated glycosaminoglycan (GAG) density produced by goat articular chondrocytes in type II collagen scaffolds prepared with a range of cross-link densities and various times in culture, The purpose of this work is to establish a basis for future studies employing constructs of selected maturity (e.g., 25%. 50%. or 75% normal GAG content) for cartilage repair in vivo. Methods: Porous scaffolds (8 mm diameter by 2 mm thick) were fabricated from porcine type II collagen by freeze-drying, followed by dehydrothermal treatment and carbodiimide cross-linking. In a pilot study, passage 3 adult caprine articular chondrocytes isolated from one goat were grown in scaffolds with six cross-link densities for 2, 3, 4, and 6 weeks (n = 3). The goal was to select scaffold cross-link densities and times in culture that would produce constructs with approximately 25%, 50% and 75% the GAG density of native articular cartilage. Based on the results of the pilot study, chondrocytes from three goats were grown in scaffolds with two cross-link densities for three time periods: 3, 5, and 9 weeks (n = 6: one of the cross-link groups was run in quadruplicate). The equilibrium modulus from unconfined compression testing of these samples was correlated with GAG content. Results: There was a notable increase in GAG density with decreasing cross-link density. Histological analysis verified a chondrogenic phenotype and revealed various amounts of GAG and type II collagen-containing cartilage. The correlation between modulus and GAG density had a linear coefficient of determination of 0.60. One group with a mean GAG density of 22 mu g/mm(3), which was 140% the GAG density of normal caprine articular cartilage, averaged a compressive modulus of 31.5 kPa, which was 10% of caprine articular cartilage tested in this study. Conclusions: The GAG density and modulus of tissue-engineered constructs can be controlled by the degree of cross-linking of type II collagen scaffolds and time in culture. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Pfeiffer, E.; Vickers, S. M.; Spector, M.] VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. [Pfeiffer, E.; Vickers, S. M.; Spector, M.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Frank, E.; Grodzinsky, A. J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Spector, M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn, 150 S Huntington Ave,Mail Stop 151, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU Office of Research and Development; Rehabilitation Research and Development Service; Department of Veterans Affairs; VA Research Career Scientist Awardee; NICHD FX This material is based upon work supported by the Office of Research and Development, Rehabilitation Research and Development Service, Department of Veterans Affairs. MIS is a VA Research Career Scientist Awardee. The type II collagen antibody developed by Holmdahl and Rubin was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. The authors would like to thank Alix Weaver for her technical support. NR 41 TC 29 Z9 30 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD OCT PY 2008 VL 16 IS 10 BP 1237 EP 1244 DI 10.1016/j.joca.2008.02.014 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 358KW UT WOS:000259916700016 PM 18406634 ER PT J AU D'Avila, A Aryana, A Thiagalingam, A Holmvang, G Schmidt, E Gutierrez, P Ruskin, JN Reddy, VY AF D'Avila, Andre Aryana, Arash Thiagalingam, Aravinda Holmvang, Godtfred Schmidt, Ehud Gutierrez, Paulo Ruskin, Jeremy N. Reddy, Vivek Y. TI Focal and linear endocardial and epicardial catheter-based cryoablation of normal and infarcted ventricular tissue SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE ablation; electrophysiology; clinical; mapping; VT; new technology ID MYOCARDIAL-INFARCTION; CORONARY-ARTERIES; RADIOFREQUENCY ABLATION; CRYOTHERMAL ABLATION; PORCINE MODEL; SINUS RHYTHM; TACHYCARDIA; ELECTROPHYSIOLOGY; CRYOSURGERY; LESIONS AB Background: This study of a chronic porcine postinfarction model examined whether linear epicardial cryoablation was capable of creating large, homogenous lesions in regions of the myocardium including scarred ventricle. Endocardial and epicardial focal cryolesions were also compared to determine if there were significant differences in lesion characteristics. Methods: Eighty focal endocardial and 28 focal epicardial cryoapplications were delivered to eight normal caprine and four normal porcine ventricular myocardium, and 21 linear cryolesions were applied along the border of infarcted epicardial tissue in a chronic porcine infarct model in six swines. Results: Focal endocardial cryolesions in normal animals measured 9.7 +/- 0.4 mm (length) by 7.3 +/- 1.4 mm (width) by 4.8 +/- 0.2 mm (depth), while epicardial lesions measured 10.2 +/- 1.4 mm (length) by 7.7 +/- 2 mm (width) by 4.6 +/- 0.9 mm (depth); P > 0.05. Linear epicardial cryolesions in the chronic porcine infarct model measured 36.5 +/- 7.8 mm (length) by 8.2 +/- 1.3 mm (width) by 6.0 +/- 1.2 mm (depth). The mean depth of linear cryolesions applied to the border of the infarct scar was 7 +/- 0.7 mm, as measured by magnetic resonance imaging. Conclusions:Cryoablation can create deep lesions when delivered to the ventricular epicardium. Endocardial and epicardial cryolesions created by a focal cryoablation catheter are similar in size and depth. The ability to rapidly create deep linear cryolesions may prove to be beneficial in substrate-based catheter ablation of ventricular arrhythmias. C1 [D'Avila, Andre; Aryana, Arash; Thiagalingam, Aravinda; Ruskin, Jeremy N.; Reddy, Vivek Y.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Holmvang, Godtfred] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Holmvang, Godtfred] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Holmvang, Godtfred] Harvard Univ, Sch Med, Boston, MA USA. [Schmidt, Ehud] Gen Elect Med Syst, Adv Sci Lab, Boston, MA USA. [Gutierrez, Paulo] Univ Sao Paulo, Dept Pathol, Heart Inst InCor, Sao Paulo, Brazil. RP D'Avila, A (reprint author), Univ Miami Hosp, Cardiac Arrhythmia Serv, 1400 NW 12th Ave,Suite 4062, Miami, FL 33136 USA. EM adavila@med.miami.edu RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009; Gutierrez, Paulo/E-6783-2012 OI d'Avila, Andre Luiz/0000-0001-8769-1411; Gutierrez, Paulo/0000-0002-9544-2359 FU CryoCathregistered mark Technologies Inc.; FAPESP [02/09116-7]; NIH K23 [HL68064-01A1] FX This work was supported in part by CryoCath (R) Technologies Inc., a FAPESP award 02/09116-7 to Dr. d'Avila, and an NIH K23 award (HL68064-01A1) to Dr. Reddy. NR 24 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD OCT PY 2008 VL 31 IS 10 BP 1322 EP 1331 DI 10.1111/j.1540-8159.2008.01184.x PG 10 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 348VH UT WOS:000259237700015 PM 18811814 ER PT J AU Shea, JA Guerra, CE Weiner, J Aguirre, AC Ravenell, KL Asch, DA AF Shea, Judy A. Guerra, Carmen E. Weiner, Janet Aguirre, Abigail C. Ravenell, Karima L. Asch, David A. TI Adapting a patient satisfaction instrument for low literate and Spanish-speaking populations: Comparison of three formats SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE health literacy; patient satisfaction; survey formats ID FUNCTIONAL HEALTH LITERACY; CAHPS(R) HOSPITAL SURVEY; DATA QUALITY; CORE SURVEY; CARE; TELEPHONE; MAIL; INSTRUCTIONS; ILLUSTRATIONS; EQUIVALENCE AB Objective: To compare responses to print versions of the Consumer Assessment of Healthcare Providers and Systems 2.0 survey (CAHPS) to those for an illustration enhanced format and a telephone based interactive voice response format. Methods: First, 2015 adult patients awaiting primary care visits completed: demographic information. Test of Functional Health Literacy (S-TOFHLA). CAHPS in one of three formats: print, illustrated, or interactive voice. A second sample of 4800 active patients was randomized to receive alternative formats. Results: Response rates for the illustrated (31.3%) and print (30.4%) formats were significantly higher than for the interactive voice format (18.1%). The results of the illustrated format were comparable to the traditional text version, but required about 2 min more to complete by both low and high literacy groups. There were almost no invalid responses for the interactive voice format, but the format was associated with lower CAHPS satisfaction scores. Conclusion: Despite extensive efforts to produce formats tailored to individuals with limited literacy, surprisingly we found no consistent advantages to either alternative format. In fact. the interactive voice format yielded lower satisfaction scores and lower response rates. Practice implications: Practitioners need to ensure the health instruments they use are aligned with literacy skills and delivery preferences of their consumers. The lack of benefit of the illustrated form does not Support investment Of resources in these formats to measure satisfaction. The interactive voice response deserves more study-do lower scores register limited access to Or use of telephones. irritation or true signal? (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Shea, Judy A.; Guerra, Carmen E.; Weiner, Janet; Aguirre, Abigail C.; Ravenell, Karima L.; Asch, David A.] Univ Penn, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Shea, Judy A.; Ravenell, Karima L.; Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Shea, Judy A.; Weiner, Janet; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Shea, JA (reprint author), Univ Penn, Dept Med, Div Gen Internal Med, 1223 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM sheaja@mail.upenn.edu OI Weiner, Janet/0000-0001-5810-5807; Asch, David/0000-0002-7970-286X FU Agency for Healthcare Research and Quality [R01 HS10299, HS10299-S] FX This study was supported by R01 HS10299 and HS10299-S from the Agency for Healthcare Research and Quality. We are indebted to our collaborators at Health Partners, particularly Michael Schaffer, Pharm. D, MBA. NR 37 TC 18 Z9 18 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD OCT PY 2008 VL 73 IS 1 BP 132 EP 140 DI 10.1016/j.pec.2008.03.026 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 356JI UT WOS:000259774100020 PM 18486414 ER PT J AU Ramirez-Schrempp, D Dorfman, DH Tien, I Liteplo, AS AF Ramirez-Schrempp, Daniela Dorfman, David H. Tien, Irene Liteplo, Andrew S. TI Bedside Ultrasound in Pediatric Emergency Medicine Fellowship Programs in the United States Little Formal Training SO PEDIATRIC EMERGENCY CARE LA English DT Article DE bedside ultrasound; pediatric emergency fellowship ID BLADDER ULTRASOUND; CHILDREN; ULTRASONOGRAPHY; TRAUMA; PHYSICIAN; PATIENT; UTILITY; CATHETERIZATION; SONOGRAPHY; CELLULITIS AB Background: Bedside ultrasound (BUS) can provide critical information in a rapid and noninvasive manner to the emergency physician. It is widely used in emergency departments (ED) throughout the nation. Literature shows that BUS shortens patient stay and increases patient satisfaction. General emergency medicine (EM) residencies incorporate BUS training in their curricula. However, there are limited data about the training that pediatric emergency medicine (PEM) fellows receive. Objective: To determine the extent of training and use of BUS in PEM fellowship programs. Methods: A 29-question survey was mailed to all (57) PEM fellowship program directors in the spring of 2006. Results: The response rate was 81% (46/57). Fifty-seven percent (26/46) of the responding PEM fellowship program directors reported that their faculty used BUS in their departments. At 50% (23/46) of programs, fellows perform BUS studies. Sixty-five percent (30/46) of PEM fellowships reported that their fellows receive some BUS training, but only 15 of these programs included BUS training in the curriculum as a 2- to 4-week ultrasound rotation. Sixty-five percent (30/46) of PEM fellowship programs had access to an ultrasound machine, but only 28% (13/46) of programs had their own machine. The main reason not to own an ultrasound machine was a lack of ultrasound expertise in their department (67%, 22/33). Bedside ultrasound training was provided by general EM physicians in 57% (17/30) of programs. Eighty-seven percent of the directors agree that BUS training would benefit their practice. The 2 factors significantly associated with the likelihood of having formal BUS training were access to an ultrasound machine (87% vs 55% P = 0.04) and presence of an adult ED with an EM residency at the program (80% vs 42% P = 0.03). Pediatric emergency medicine fellowship programs at children's hospitals were significantly less likely to have formal training (33.3% vs 74.2%; P = 0.01). Conclusions: Despite literature supporting the benefits of BUS in the ED, many PEM fellowship programs do not incorporate BUS training for their PEM fellows. Most PEM fellows who receive training in BUS are instructed by physicians trained in EM, not PEM. C1 [Ramirez-Schrempp, Daniela; Dorfman, David H.] Boston Univ, Med Ctr, Boston, MA 02118 USA. [Tien, Irene] Newton Wellesley Hosp, Newton, MA USA. [Liteplo, Andrew S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ramirez-Schrempp, D (reprint author), Boston Univ, Med Ctr, 91 E Concord St,6th Floor, Boston, MA 02118 USA. EM daniela.ramirez-schrempp@bmc.org NR 24 TC 27 Z9 27 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD OCT PY 2008 VL 24 IS 10 BP 664 EP 667 DI 10.1097/PEC.0b013e3181884955 PG 4 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 361WF UT WOS:000260157500004 PM 19242134 ER PT J AU Chen, YW Tran, S Chenier, I Chan, JSD Ingelfinger, JR Inagami, T Zhang, SL AF Chen, Yun-Wen Tran, Stella Chenier, Isabelle Chan, John S. D. Ingelfinger, Julie R. Inagami, Tadashi Zhang, Shao-Ling TI Deficiency of intrarenal angiotensin II type 2 receptor impairs paired homeo box-2 and N-myc expression during nephrogenesis SO PEDIATRIC NEPHROLOGY LA English DT Article DE AT(2)R knock-out; nephrogenesis ID PROXIMAL TUBULAR CELLS; URETERAL BUD APOPTOSIS; URINARY-TRACT; CONGENITAL-ANOMALIES; KIDNEY DEVELOPMENT; AT(2) RECEPTOR; RENAL HYPOPLASIA; PAX-2 EXPRESSION; BLOOD-PRESSURE; MICE LACKING AB We previously demonstrated that angiotensin II (Ang II) stimulates paired homeo box-2 (Pax-2) via the Ang II type 2 receptor (AT(2)R). The Pax-2 gene and N-myc play pivotal roles in renal morphogenesis via their effects on cell proliferation and differentiation in embryonic mesenchymal cells and embryonic mouse kidneys. Since AT(2)R knock-out (KO) mice have a phenotype that is similar to that of humans with congenital renal and urinary tract anomalies (CAKUT) and develop hypertension in adulthood, these mice and wild-type controls were used for this study. Embryonic kidneys isolated from E12 to term gestation were cultured in Dulbecco's modified Eagle's medium (DMEM) with or without Ang II (10(-6) M) for 24 h ex vivo. Renal morphogenesis was histologically assessed. Mean glomerular tuft volume was determined by the method of Weibel and Gomez with the aid of image analysis software. Pax-2 and N-myc gene expression were determined by immunostaining as well as by Western blotting and real-time-quantitative polymerase chain reaction (RT-qPCR). Glomerular size was significantly smaller, and Pax-2 and N-myc expression down-regulated, in kidneys of AT(2)R KO mice compared with those of wild-type mice. In ex vivo studies, Ang II stimulated Pax-2 and N-myc mRNA expression in embryonic kidneys of wild-type mice, but this stimulatory effect was absent in embryonic kidneys of AT(2)R KO mice. Taken together, these data indicate that intrarenal AT(2)R plays an important role in nephrogenesis. Deficiency of AT(2)R may impair both Pax-2 and N-myc expression, eventually resulting in glomerular hyperfiltration that may, ultimately, lead to later development of hypertension. C1 [Chen, Yun-Wen; Tran, Stella; Chenier, Isabelle; Chan, John S. D.; Zhang, Shao-Ling] CHUM Hotel Dieu, Res Ctr, Montreal, PQ H2W 1T7, Canada. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. [Inagami, Tadashi] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37212 USA. RP Zhang, SL (reprint author), CHUM Hotel Dieu, Res Ctr, 3850 St Urbain St, Montreal, PQ H2W 1T7, Canada. EM shao.ling.zhang@umontreal.ca FU Massachusetts General Hospital, Boston, USA; Kidney Research Scientist Core Education and National Training (KRESCENT); Kidney Foundation of Canada (KFOC) FX The authors acknowledge the kind gifts of AT2R knock-out mice (AT2R KO) from Dr. Tadashi Inagami (Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA). Thanks are also due to Dr. John S. D. Chan (Centre hospitalier de l'Universite de Montreal-Hotel-Dieu, Montreal, Quebec, Canada) and Dr. Julie R. Ingelfinger (Massachusetts General Hospital, Boston, USA) for their unconditional support and discussion in this project. This research was supported by the Kidney Research Scientist Core Education and National Training (KRESCENT) program and the Kidney Foundation of Canada (KFOC) and a New Investigator Award from KRESCENT of the Kidney Foundation of Canada to Dr. Shao-Ling Zhang. The editorial assistance of Ovid Da Silva, Research Support Office, Research Centre, Centre hospitalier de l'Universite de Montreal, is acknowledged. NR 55 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD OCT PY 2008 VL 23 IS 10 BP 1769 EP 1777 DI 10.1007/s00467-008-0854-6 PG 9 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 344CH UT WOS:000258902600006 PM 18607644 ER PT J AU Tierney, TS Tierney, BJ Rosenberg, AE Krishnamoorthy, KS Butler, WE AF Tierney, Travis S. Tierney, Brent J. Rosenberg, Andrew E. Krishnamoorthy, Kalpathy S. Butler, William E. TI Infantile Myofibromatosis: A Nontraumatic Cause of Neonatal Brachial Plexus Palsy SO PEDIATRIC NEUROLOGY LA English DT Article AB Most injuries to the neonatal brachial plexus occur acutely at birth, and are iatrogenic in origin. However, when weakness is accompanied by atrophy, nontraumatic etiologies should be considered. The differential diagnosis of chronic congenital brachial plexopathy includes cervical bone malformations, humeral osteomyelitis, varicella, and compression from various types of infantile tumors. An illustrative male infant delivered at 37 weeks of gestation with wasted musculature of the left upper arm, ipsilateral Horner's syndrome, and a hemidiaphragm is presented. On further examination, this patient manifested an underlying cervical tumor compressing the brachial plexus. Diagnostic steps leading to the pathologic identification of a solitary cervical myofibroma included physical examination, electromyography, radiographic imaging, and open biopsy. This report emphasizes the importance of differentiating acute from chronic congenital plexus palsy and of recognizing the possibility that infection or neoplasm may underlie the latter. (C) 2008 by Elsevier Inc. All rights reserved. C1 [Tierney, Travis S.; Butler, William E.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Tierney, Brent J.] Creighton Univ, Med Ctr, Dept Obstet & Gynecol, Omaha, NE USA. [Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Krishnamoorthy, Kalpathy S.] Massachusetts Gen Hosp, Pediat Neurol Serv, Boston, MA 02114 USA. RP Tierney, TS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, 55 Fruit St,White 502, Boston, MA 02114 USA. EM tstierney@partners.org NR 10 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD OCT PY 2008 VL 39 IS 4 BP 276 EP 278 DI 10.1016/j.pediatrneurol.2008.06.009 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 363RU UT WOS:000260285200009 PM 18805367 ER PT J AU Prabhu, SP Tran, B AF Prabhu, Sanjay P. Tran, Brandon TI Pneumoparotitis SO PEDIATRIC RADIOLOGY LA English DT Editorial Material C1 [Prabhu, Sanjay P.] Childrens Hosp, Dept Neuroradiol, Boston, MA 02115 USA. [Tran, Brandon] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Prabhu, SP (reprint author), Childrens Hosp, Dept Neuroradiol, 300 Longwood Ave, Boston, MA 02115 USA. EM sanjay.prabhu@childrens.harvard.edu NR 2 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2008 VL 38 IS 10 BP 1144 EP 1144 DI 10.1007/s00247-008-0930-x PG 1 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 346QJ UT WOS:000259083600023 PM 18626637 ER PT J AU Goldstein, AM Nagy, N AF Goldstein, Allan M. Nagy, Nandor TI A bird's eye view of enteric nervous system development: Lessons from the avian embryo SO PEDIATRIC RESEARCH LA English DT Review ID NEURAL CREST CELLS; ENDOTHELIN-B RECEPTOR; TYROSINE KINASE RET; HIRSCHSPRUNGS-DISEASE; EXPRESSION PATTERN; HINDGUT COLONIZATION; CHICKEN GENOME; WAVE-FRONT; IN-VITRO; NEURONS AB The avian embryo has been an important model system for studying enteric nervous system (ENS) development for over 50 y. Since the initial demonstration in chick embryos that the ENS is derived from the neural crest, investioators have used the avian model to reveal the cellular origins and migratory pathways of enteric neural crest-derived cells, with more recent work focusing on the molecular mechanisms regulating ENS development. Seminal contributions have been made in this field by researchers who have taken advantage of the strengths of the avian model system. These strengths include in vivo accessibility throughout development, ability to generate quail-chick chimeras, and the capacity to modulate gene expression in vivo in a spatially and temporally targeted manner. The recent availability of the chicken genome further enhances this model system, allowing investigators to combine classic embryologic methods with current genetic techniques. The strengths and versatility of the avian embryo Continue to make it a valuable experimental system for studying the development of the ENS. C1 [Goldstein, Allan M.] Harvard Univ, Sch Med, Dept Pediat Surg, Boston, MA 02114 USA. [Goldstein, Allan M.] Harvard Univ, Sch Med, Pediat Intestinal Rehabil Program, Boston, MA 02114 USA. [Nagy, Nandor] Semmelweis Univ, Dept Human Morphol & Dev Biol, H-1094 Budapest, Hungary. RP Goldstein, AM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org FU NIH [K08HD46655]; American pediatric Surgical Association Foundation; Hungarian Scientific Research Fund [K-69061]; Semmelweis University FX Supported by NIH K08HD46655 and the American pediatric Surgical Association Foundation (to A.M.G.) and a grant front the Hungarian Scientific Research Fund (K-69061) and a Young Investigator Award from Semmelweis University (to N.N). NR 69 TC 15 Z9 16 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 2008 VL 64 IS 4 BP 326 EP 333 DI 10.1203/PDR.0b013e31818535e8 PG 8 WC Pediatrics SC Pediatrics GA 352YA UT WOS:000259532100002 PM 18636038 ER PT J AU Homer, CJ Klatka, K Romm, D Kuhlthau, K Bloom, S Newacheck, P Van Cleave, J Perrin, JM AF Homer, Charles J. Klatka, Kirsten Romm, Diane Kuhlthau, Karen Bloom, Sheila Newacheck, Paul Van Cleave, Jeanne Perrin, James M. TI A review of the evidence for the medical home for children with special health care needs SO PEDIATRICS LA English DT Review DE medical home; special needs children; systematic review; family-centered care ID PEDIATRIC-ASTHMA-CARE; OUTCOMES-RESEARCH-TEAM; QUALITY IMPROVEMENT; PATIENT-OUTCOMES; CHRONIC ILLNESS; COORDINATED CARE; NATIONAL-SURVEY; FAMILY; EMERGENCY; ACCESS AB CONTEXT. The receipt of health care in a medical home is increasingly touted as a fundamental basis for improved care for persons with chronic conditions, yet the evidence for this claim has not been systematically assessed. OBJECTIVE. Our goal was to determine the evidence for the federal Maternal and Child Health Bureau recommendation that children with special health care needs receive ongoing comprehensive care within a medical home. METHODS. We searched the nursing and medical literature, references of selected articles, and requested expert recommendations. Search terms included children with special health care needs, medical home-related interventions, and health-related outcomes. Articles that met defined criteria (eg, children with special health care needs, United States-based, quantitative) were selected. We extracted data, including design, population characteristics, sample size, intervention, and findings from each article. RESULTS. We selected 33 articles that reported on 30 distinct studies, 10 of which were comparison-group studies. None of the studies examined the medical home in its entirety. Although tempered by weak designs, inconsistent definitions and extent of medical home attributes, and inconsistent outcome measures, the preponderance of evidence supported a positive relationship between the medical home and desired outcomes, such as better health status, timeliness of care, family centeredness, and improved family functioning. CONCLUSIONS. The evidence provides moderate support for the hypothesis that medical homes provide improved health-related outcomes for children with special health care needs. Additional studies with comparison groups encompassing all or most of the attributes of the medical home need to be undertaken. C1 [Klatka, Kirsten; Romm, Diane; Kuhlthau, Karen; Bloom, Sheila] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Homer, Charles J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Homer, Charles J.] Natl Initiat Childrens Healthcare Qual, Cambridge, MA USA. [Kuhlthau, Karen; Van Cleave, Jeanne; Perrin, James M.] Harvard Univ, Sch Med, Boston, MA USA. [Newacheck, Paul; Van Cleave, Jeanne; Perrin, James M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Newacheck, Paul; Van Cleave, Jeanne; Perrin, James M.] Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Klatka, K (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM kklatka@partners.org RI eshaghian, azam/Q-8826-2016 OI eshaghian, azam/0000-0001-7918-2895 FU MCHB [U53MC04473-03-00] FX We thank our funders at the MCHB (Cooperative Agreement 5 U53MC04473-03-00) for support. NR 58 TC 158 Z9 161 U1 4 U2 16 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 IS 4 BP E922 EP E937 DI 10.1542/peds.2007-3762 PG 16 WC Pediatrics SC Pediatrics GA 356YD UT WOS:000259812600062 PM 18829788 ER PT J AU Kitami, T Rubio, R O'Brien, W Quackenbush, J Nadeau, JH AF Kitami, Toshimori Rubio, Renee O'Brien, William Quackenbush, John Nadeau, Joseph H. TI Gene-environment interactions reveal a homeostatic role for cholesterol metabolism during dietary folate perturbation in mice SO PHYSIOLOGICAL GENOMICS LA English DT Article ID NEURAL-TUBE DEFECTS; FOLIC-ACID SUPPLEMENTATION; SYNTHASE-DEFICIENT MICE; CORONARY-HEART-DISEASE; LEMLI-OPITZ-SYNDROME; METHIONINE SYNTHASE; PLASMA HOMOCYSTEINE; VASCULAR DYSFUNCTION; EMBRYONIC LETHALITY; CDNA MICROARRAY AB Kitami T, Rubio R, O'Brien W, Quackenbush J, Nadeau JH. Gene-environment interactions reveal a homeostatic role for cholesterol metabolism during dietary folate perturbation in mice. Physiol Genomics 35: 182-190, 2008. First published August 12, 2008; doi:10.1152/physiolgenomics.00294.2007.-Dietary folate supplementation can dramatically reduce the severity and incidence of several common birth defects and adult diseases that are associated with anomalies in homocysteine and folate metabolism. The common polymorphisms that adversely affect these metabolic pathways do not fully account for the particular birth defects and adult diseases that occur in at-risk individuals. To test involvement of folate, homocysteine, and other pathways in disease pathogenesis and treatment response, we analyzed global and pathway-specific changes in gene expression and levels of selected metabolites after depletion and repletion of dietary folate in two genetically distinct inbred strains of mice. Compared with the C57BL/6J strain, A/J showed greater homeostatic response to folate perturbation by retaining a higher serum folate level and minimizing global gene expression changes. Remarkably, folate perturbation led to systematic strain-specific differences only in the expression profile of the cholesterol biosynthesis pathway and to changes in levels of serum and liver total cholesterol. By genetically increasing serum and liver total cholesterol levels in APOE-deficient mice, we modestly but significantly improved folate retention during folate depletion, suggesting that homeostasis among the homocysteine, folate and cholesterol metabolic pathways contributes to the beneficial effects of dietary folate supplementation. C1 [Nadeau, Joseph H.] Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. [Kitami, Toshimori; Nadeau, Joseph H.] Case Western Reserve Univ, Ctr Computat Genom & Syst Biol, Cleveland, OH 44106 USA. [Rubio, Renee; Quackenbush, John] Inst Genom Res, Rockville, MD USA. [Rubio, Renee; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rubio, Renee; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [O'Brien, William] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Nadeau, JH (reprint author), Case Western Reserve Univ, Sch Med, Dept Genet, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM jhn4@case.edu FU National Heart, Lung, and Blood Institute [HL-58982, HL-66580, HL-73712] FX This work was supported by National Heart, Lung, and Blood Institute Grant HL-58982 (J. H. Nadeau), HL-66580 (J. Quackenbush), HL-73712 (J. Quackenbush), and a gift from the Charles B. Wang Foundation (J. H. Nadeau). NR 66 TC 12 Z9 12 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD OCT PY 2008 VL 35 IS 2 BP 182 EP 190 DI 10.1152/physiolgenomics.00294.2007 PG 9 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 433QC UT WOS:000265219900006 PM 18697859 ER PT J AU Tran, TNT Schulman, J Fisher, DE AF Tran, Thanh-Nga T. Schulman, Joshua Fisher, David E. TI UV and pigmentation: molecular mechanisms and social controversies SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; ULTRAVIOLET-LIGHT EXPOSURE; SERUM VITAMIN-D; SKIN-CANCER; DNA-DAMAGE; POPULAR ATTITUDES; UNITED-STATES; XERODERMA-PIGMENTOSUM; MUTATION HOTSPOTS; OXIDATIVE DAMAGE AB Ultraviolet radiation (UVR) is an essential risk factor for the development of premalignant skin lesions as well as of melanoma and non-melanoma skin cancer. UVR exerts many effects on the skin, including tanning, carcinogenesis, immunomodulation, and production of vitamin D. Vitamin D (vit D) is important in the maintenance of healthy bones as well as other purported beneficial effects, amongst which is the potential for reducing risk of malignancy-though oral supplementation is fully capable of maintaining systemic levels. The known medical harm from UV exposure relates primarily to cancer of the skin-the most common organ in man to be affected by cancer. In this review, we summarize the knowledge about the ultraviolet (UV) response in regards to inflammation, immunosuppression, carcinogenesis and the tanning response. We also discuss vit D and UV, as well as public health implications of tanning behavior and commercial interests related to the promotion of UV exposure. As the most ubiquitous human carcinogen, UVR exposure represents both a challenge and enormous opportunity in the realm of skin cancer prevention. C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Melanoma Program, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. EM Dfisher3@partners.org FU NIH FX The authors gratefully acknowledge useful comments from Drs. Marianne Berwick and Dot Bennett. David E. Fisher is Distinguished Clinical Scholar of the Doris Duke Medical Research Foundation and acknowledges research support from NIH. NR 83 TC 45 Z9 46 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD OCT PY 2008 VL 21 IS 5 BP 509 EP 516 DI 10.1111/j.1755-148X.2008.00498.x PG 8 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 350KW UT WOS:000259352300006 PM 18821855 ER PT J AU Petricka, JJ Clay, NK Nelson, TM AF Petricka, Jalean Joyanne Clay, Nicole Kho Nelson, Timothy Mark TI Vein patterning screens and the defectively organized tributaries mutants in Arabidopsis thaliana SO PLANT JOURNAL LA English DT Article DE vein patterning; glycine-rich protein; C2H2 zinc finger WIP domain; NON-PHOTOTROPHIC HYPOCOTYL 3; SART-1; pentatricopeptide repeat; genetic screen ID POLAR AUXIN TRANSPORT; ZINC-FINGER PROTEINS; CELL-CYCLE ARREST; VENATION PATTERNS; UBIQUITIN LIGASES; VASCULAR NETWORK; MUTATION AFFECTS; ARF-GAP; L HEYNH; LEAF AB Leaf veins form a closed network that transports essential photosynthates, water and signaling molecules to the developing plant. The formation of the patterns of these networks during leaf ontogeny is an active subject of modeling and computer simulation. To investigate the vein patterning process, we performed screens for defects in juvenile leaf vein patterning in Arabidopsis thaliana lines subjected to mutagenesis via diepoxybutane, activation tagging or the Dissociation/Activator transposon. We identified over 40 vein pattern defective lines, providing a phenotypic resource for the testing of vein patterning models. In addition, we report the chromosomal linkage for 13 of these, eight of which were successfully cloned. We further describe the phenotypes of five of these mutants, which we call the defectively organized tributaries (dot) mutants, and their corresponding molecular identities. The diversity of the individual genes affected in this collection of pattern mutants suggests that vein pattern is highly sensitive to perturbations in many cellular processes. Despite this diversity of causes, the resulting pattern defects fall into a limited number of classes, including parallel, spurred, misaligned, open, midvein gap and irregularly spaced. These classes may represent sensitivities to cellular processes associated with the DOT genes. The ontogeny of common defective patterns should be accommodated into any robust model for the ontogeny and evolution of pattern. C1 [Petricka, Jalean Joyanne; Clay, Nicole Kho; Nelson, Timothy Mark] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. [Petricka, Jalean Joyanne] Duke Univ, Dept Biol, French Family Sci Ctr, Durham, NC 27703 USA. [Clay, Nicole Kho] Harvard Univ, Massachusetts Gen Hosp, Dept Biol, Boston, MA 02114 USA. RP Nelson, TM (reprint author), Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. EM timothy.nelson@yale.edu FU NSF [IBN-0416731] FX Sequencing analysis was performed by the HHMI Biopolymer/Keck Foundation Biotechnology Resource Laboratory (Yale University, New Haven, CT, USA). Ds, activation tagging and Salk lines, as well as TAC filters, clones and cDNAs, were obtained from ABRC (http://www.biosci.ohio-state.edu/pcmb/Facilities/abrc/abrchome.htm). This work was supported by NSF Grant IBN-0416731 to TN. NR 82 TC 31 Z9 37 U1 2 U2 22 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0960-7412 J9 PLANT J JI Plant J. PD OCT PY 2008 VL 56 IS 2 BP 251 EP 263 DI 10.1111/j.1365-313X.2008.03595.x PG 13 WC Plant Sciences SC Plant Sciences GA 358KA UT WOS:000259914500007 PM 18643975 ER PT J AU Taghinia, AH Liao, EC May, JW AF Taghinia, Amir H. Liao, Eric C. May, James W., Jr. TI Randomized controlled trials in plastic surgery: A 20-year review of reporting standards, methodologic quality, and impact SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CLINICAL-TRIALS; CONSORT STATEMENT; STATISTICS NOTES; SURGICAL TRIALS; CONSOLIDATED STANDARDS; MEDICAL JOURNALS; SAMPLE-SIZE; INFORMATION; RELIABILITY; GYNECOLOGY AB Background: Randomized controlled trials in plastic surgery have not been analyzed comprehensively. We analyzed plastic surgical randomized controlled trials with respect to reporting standards, methodologic quality, and impact on the specialty. Methods: Randomized controlled trials published from 1986 to 2006 in three major plastic surgery journals were scored for quality and impact using the Consolidated Standards of Reporting Trials checklist, the Jadad criteria, citation numbers, and other parameters. The associations between the quality scores and multiple independent parameters, including trial impact, were explored. The relative impact of randomized controlled trials in plastic surgery was compared with that in other specialties. Results: A total of 163 randomized controlled trials were evaluated. The average Consolidated Standards of Reporting Trials and Jadad scores were 49 percent and 2.3, respectively. There were deficiencies in the reporting of parameters that influence bias and statistical significance. Randomized controlled trials with high impact or high methodologic quality had higher reporting scores. However, the quality and impact scores did not correlate with the number of participants, subject category, country of origin, or year or journal of publication. Nonsurgical trials had significantly higher quality and impact than surgical trials. Randomized controlled trials in plastic surgery had relatively lower impact as compared with randomized controlled trials in other specialties. Conclusions: The reporting and methodologic standards of randomized controlled trials in plastic surgery need improvement. Standards could be improved if well-accepted reporting and methodologic criteria are considered when designing and evaluating randomized controlled trials. Instituting higher standards may improve the impact of randomized controlled trials and make them more influential in plastic surgery. C1 [Taghinia, Amir H.] Harvard Univ, Childrens Hosp, Dept Plast Surg, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02115 USA. RP Taghinia, AH (reprint author), Harvard Univ, Childrens Hosp, Dept Plast Surg, Sch Med, 300 Longwood Ave,Hunnewell 1, Boston, MA 02115 USA. EM amir.taghinia@childrens.harvard.edu NR 69 TC 18 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 2008 VL 122 IS 4 BP 1253 EP 1263 DI 10.1097/PRS.0b013e3181858f16 PG 11 WC Surgery SC Surgery GA 356XU UT WOS:000259811700034 PM 18827662 ER PT J AU Ku, M Koche, RP Rheinbay, E Mendenhall, EM Endoh, M Mikkelsen, TS Presser, A Nusbaum, C Xie, XH Chi, AS Adli, M Kasif, S Ptaszek, LM Cowan, CA Lander, ES Koseki, H Bernstein, BE AF Ku, Manching Koche, Richard P. Rheinbay, Esther Mendenhall, Eric M. Endoh, Mitsuhiro Mikkelsen, Tarjei S. Presser, Aviva Nusbaum, Chad Xie, Xiaohui Chi, Andrew S. Adli, Mazhar Kasif, Simon Ptaszek, Leon M. Cowan, Chad A. Lander, Eric S. Koseki, Haruhiko Bernstein, Bradley E. TI Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains SO PLOS GENETICS LA English DT Article ID EMBRYONIC STEM-CELLS; GROUP PROTEINS RING1A/B; RNA-POLYMERASE-II; NF-KAPPA-B; DEVELOPMENTAL REGULATORS; DROSOPHILA-MELANOGASTER; POLYCOMB TARGETS; HISTONE H2A; GENE FAMILY; ES CELLS AB In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3 lysine 27 tri-methylation) and activating (H3 lysine 4 tri-methylation) histone modifications mark the promoters of more than 2,000 genes. To gain insight into the structure and function of bivalent domains, we mapped key histone modifications and subunits of Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2) genomewide in human and mouse ES cells by chromatin immunoprecipitation, followed by ultra high-throughput sequencing. We find that bivalent domains can be segregated into two classes-the first occupied by both PRC2 and PRC1 (PRC1-positive) and the second specifically bound by PRC2 (PRC2-only). PRC1-positive bivalent domains appear functionally distinct as they more efficiently retain lysine 27 tri-methylation upon differentiation, show stringent conservation of chromatin state, and associate with an overwhelming number of developmental regulator gene promoters. We also used computational genomics to search for sequence determinants of Polycomb binding. This analysis revealed that the genomewide locations of PRC2 and PRC1 can be largely predicted from the locations, sizes, and underlying motif contents of CpG islands. We propose that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting the full repertoire of Polycomb complexes in pluripotent cells. C1 [Ku, Manching; Koche, Richard P.; Rheinbay, Esther; Mendenhall, Eric M.; Chi, Andrew S.; Adli, Mazhar; Bernstein, Bradley E.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Ku, Manching; Koche, Richard P.; Rheinbay, Esther; Mendenhall, Eric M.; Chi, Andrew S.; Adli, Mazhar; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Ku, Manching; Mendenhall, Eric M.; Adli, Mazhar; Bernstein, Bradley E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Koche, Richard P.; Mikkelsen, Tarjei S.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Ku, Manching; Koche, Richard P.; Rheinbay, Esther; Mendenhall, Eric M.; Mikkelsen, Tarjei S.; Presser, Aviva; Nusbaum, Chad; Chi, Andrew S.; Adli, Mazhar; Lander, Eric S.; Bernstein, Bradley E.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Rheinbay, Esther; Kasif, Simon] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Rheinbay, Esther; Kasif, Simon] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Endoh, Mitsuhiro; Koseki, Haruhiko] RIKEN, Res Ctr Allergy & Immunol, Tsurumi Ku, Yokohama, Kanagawa, Japan. [Presser, Aviva] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Xie, Xiaohui] Univ Calif Irvine, Dept Comp Sci, Irvine, CA USA. [Ptaszek, Leon M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ptaszek, Leon M.; Cowan, Chad A.; Bernstein, Bradley E.] Harvard Stem Cell Inst, Cambridge, MA USA. [Ptaszek, Leon M.; Cowan, Chad A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Stowers Med Inst, Ctr Regenerat Med, Boston, MA 02114 USA. [Lander, Eric S.] MIT, Whitehead Inst Biomed Res, Cambridge, MA USA. RP Ku, M (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. EM Bernstein.Bradley@mgh.harvard.edu RI Mikkelsen, Tarjei/A-1306-2007; Koseki, Haruhiko/I-3825-2014; OI Mikkelsen, Tarjei/0000-0002-8133-3135; Koseki, Haruhiko/0000-0001-8424-5854; Mendenhall, Eric/0000-0002-7395-6295 FU Croucher Foundation; National Human Genome Research Institute; NIH [R01 HG003367-01A1]; National Cancer Institute; Genome Network Project; Burroughs Wellcome Fund; Culpeper Foundation; Harvard Stem Cell Institute; Massachusetts General Hospital; Broad Institute of Harvard; MIT FX MK is supported by the Croucher Foundation. ER is supported by an institutional training grant from the National Human Genome Research Institute. SK and ER were funded in part by NIH grant R01 HG003367-01A1. EM is supported by an institutional training grant from the National Cancer Institute. HK is supported by the Genome Network Project. This research was supported by funds from the National Human Genome Research Institute, the Burroughs Wellcome Fund, the Culpeper Foundation, the Harvard Stem Cell Institute, Massachusetts General Hospital, and the Broad Institute of Harvard and MIT. NR 65 TC 526 Z9 539 U1 3 U2 31 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2008 VL 4 IS 10 AR e1000242 DI 10.1371/journal.pgen.1000242 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 380QS UT WOS:000261480900037 PM 18974828 ER PT J AU Nelson, EJ Chowdhury, A Flynn, J Schild, S Bourassa, L Shao, Y LaRocque, RC Calderwood, SB Qadri, F Camilli, A AF Nelson, Eric J. Chowdhury, Ashrafuzzaman Flynn, James Schild, Stefan Bourassa, Lori Shao, Yue LaRocque, Regina C. Calderwood, Stephen B. Qadri, Firdausi Camilli, Andrew TI Transmission of Vibrio cholerae Is Antagonized by Lytic Phage and Entry into the Aquatic Environment SO PLOS PATHOGENS LA English DT Article ID BACTERIUM THERMOTOGA-MARITIMA; INTESTINAL COLONIZATION; SEASONAL CHOLERA; POLYACRYLAMIDE GELS; BIOFILM FORMATION; MICROARRAY DATA; EL-TOR; BANGLADESH; O1; BACTERIOPHAGE AB Cholera outbreaks are proposed to propagate in explosive cycles powered by hyperinfectious Vibrio cholerae and quenched by lytic vibriophage. However, studies to elucidate how these factors affect transmission are lacking because the field experiments are almost intractable. One reason for this is that V. cholerae loses the ability to culture upon transfer to pond water. This phenotype is called the active but non-culturable state (ABNC; an alternative term is viable but non-culturable) because these cells maintain the capacity for metabolic activity. ABNC bacteria may serve as the environmental reservoir for outbreaks but rigorous animal studies to test this hypothesis have not been conducted. In this project, we wanted to determine the relevance of ABNC cells to transmission as well as the impact lytic phage have on V. cholerae as the bacteria enter the ABNC state. Rice-water stool that naturally harbored lytic phage or in vitro derived V. cholerae were incubated in a pond microcosm, and the culturability, infectious dose, and transcriptome were assayed over 24 h. The data show that the major contributors to infection are culturable V. cholerae and not ABNC cells. Phage did not affect colonization immediately after shedding from the patients because the phage titer was too low. However, V. cholerae failed to colonize the small intestine after 24 h of incubation in pond water-the point when the phage and ABNC cell titers were highest. The transcriptional analysis traced the transformation into the non-infectious ABNC state and supports models for the adaptation to nutrient poor aquatic environments. Phage had an undetectable impact on this adaptation. Taken together, the rise of ABNC cells and lytic phage blocked transmission. Thus, there is a fitness advantage if V. cholerae can make a rapid transfer to the next host before these negative selective pressures compound in the aquatic environment. C1 [Nelson, Eric J.; Bourassa, Lori; Camilli, Andrew] Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA. [Nelson, Eric J.; Bourassa, Lori; Camilli, Andrew] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Chowdhury, Ashrafuzzaman] Jahangirnagar Univ, Dept Microbiol, Dhaka, Bangladesh. [Flynn, James; Shao, Yue] Tufts Univ, Sch Med, Tufts Express Array Core Facil, Boston, MA 02111 USA. [Schild, Stefan] Karl Franzens Univ Graz, Inst Mol Biowissensch, Graz, Austria. [LaRocque, Regina C.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. RP Nelson, EJ (reprint author), Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA. EM andrew.camilli@tufts.edu OI Schild, Stefan/0000-0001-7842-0177 FU National Institutes of Health [R01 AI 055058, UO1 AI 058935, RO3 AI063079]; International Research Scientist Development Award [K01 TW007144]; Fogarty International Center at the National Institutes of Health [D43 TW005572] FX The research was supported by the National Institutes of Health R01 AI 055058 (A. C.), UO1 AI 058935 (S. B. C.), RO3 AI063079 (F. Q.), and International Research Scientist Development Award K01 TW007144 (R. C. L.). A. Camilli is a Howard Hughes Medical Institute investigator. E. J. Nelson is a recipient of the Fogarty/Ellison Fellowship in Global Health awarded by the Fogarty International Center at the National Institutes of Health (D43 TW005572). NR 69 TC 41 Z9 41 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2008 VL 4 IS 10 AR e1000187 DI 10.1371/journal.ppat.1000187 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 380QU UT WOS:000261481100020 PM 18949027 ER PT J AU Huang, R Barber, TA Schmidt, MA Tompkins, RG Toner, M Bianchi, DW Kapur, R Flejter, WL AF Huang, R. Barber, T. A. Schmidt, M. A. Tompkins, R. G. Toner, M. Bianchi, D. W. Kapur, R. Flejter, W. L. TI A microfluidics approach for the isolation of nucleated red blood cells (NRBCs) from the peripheral blood of pregnant women SO PRENATAL DIAGNOSIS LA English DT Article DE microfluidcs; nucleated red blood cells; noninvasive prenatal diagnosis ID NONINVASIVE PRENATAL-DIAGNOSIS; FETAL DNA DIAGNOSIS; MATERNAL BLOOD; DENSITY GRADIENT; ANEUPLOID PREGNANCIES; FLOW-CYTOMETRY; ENRICHMENT; ERYTHROBLASTS; ERYTHROCYTES; SEPARATION AB Objective Nucleated red blood cells (NRBCs) have been identified in maternal circulation and potentially provide a resource for the monitoring and diagnosis of maternal, fetal, and neonatal health and disease. Past strategies used to isolate and enrich for NRBCs are limited to complex approaches that result in low recovery and less than optiamal cell purity. Here we report the development of a high-throughput and highly efficient microfluidic device for isolating rare NRBCs from maternal blood. Material and Methods NRBCs were isolated from the peripheral blood of 58 pregnant women using a microfluidic process that consists of a microfluidic chip for size-based cell separation and a magnetic device her hemoglobin-based cell isolation. Results The microfluidic-magnetic combination removes nontarget red blood cells and white blood cells at a very high efficiency (similar to 99.99%). The device successfully identified NRBCs from the peripheral blood of 58/58 pretermination samples with a mean of 37.44 NRBC/mL (range 0.37-274.36 NRBC/mL). These results were compared with those from previous studies. Conclusion The microfluidic device results in an approximate 10- to 20-fold enrichment of NRBCs over methods described previously. The reliability of isolation and the purity of the NRBC product have the potential to enable the subsequent application of molecular diagnostic assays. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Huang, R.; Barber, T. A.; Kapur, R.; Flejter, W. L.] Artemis Hlth Inc, Menlo Pk, CA USA. [Schmidt, M. A.] MIT, Cambridge, MA 02139 USA. [Tompkins, R. G.; Toner, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, BioMicroElectroMech Syst Resource Ctr & Surg Serv, Boston, MA USA. [Tompkins, R. G.; Toner, M.] Shriners Hosp Children, Boston, MA USA. [Bianchi, D. W.] Tufts Univ, Sch Med, Dept Pediat, Boston, MA 02111 USA. RP Flejter, WL (reprint author), Caris Diagnost, 4207 E Cotton Ctr Blvd, Phoenix, AZ 85040 USA. EM wflejter@carisdx.com FU NIBIB NIH HHS [P41 EB002503] NR 32 TC 64 Z9 66 U1 7 U2 46 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD OCT PY 2008 VL 28 IS 10 BP 892 EP 899 DI 10.1002/pd.2079 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 364RB UT WOS:000260351700002 PM 18821715 ER PT J AU Sabir, IN Killeen, MJ Grace, AA Huang, CLH AF Sabir, Ian N. Killeen, Matthew J. Grace, Andrew A. Huang, Christopher L. -H. TI Ventricular arrhythmogenesis: Insights from murine models SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE Murine hearts; Cardiac arrhythmogenesis; Sudden cardiac death ID LONG-QT SYNDROME; SUDDEN CARDIAC DEATH; ST-SEGMENT ELEVATION; TORSADE-DE-POINTES; LANGE-NIELSEN-SYNDROME; RABBIT ATRIAL MUSCLE; CHANNEL GENE SCN5A; INDUCED DELAYED AFTERDEPOLARIZATIONS; ELECTROCARDIOGRAPHIC J-WAVE; ACTION-POTENTIAL DURATION AB Ventricular arrhythmias are the key underlying cause of sudden cardiac death, a common cause of mortality and a significant public health burden. Insights into the electrophysiological basis of such phenomena have been obtained using a wide range of recording techniques and a diversity of experimental models. As in other Fields of biology, tire murine system presents both a wealth of opportunities and important challenges when employed to model the human case. This article begins by reviewing the extent to which the murine heart is representative of that of the human. It then presents a novel physiological classification of mechanisms of arrhythmogenesis, critically assessing the extent to which of murine hearts has offered worthwhile insights. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Sabir, Ian N.; Huang, Christopher L. -H.] Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England. [Killeen, Matthew J.] Harvard Univ, Sch Med, Charlestown, MA USA. [Killeen, Matthew J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Grace, Andrew A.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. RP Sabir, IN (reprint author), Univ Cambridge, Physiol Lab, Downing St, Cambridge CB2 3EG, England. EM ins20@cam.ac.uk FU University of Cambridge; Wellcome Trust; British Heart Foundation FX We are grateful to the James Baird, Frank Elmore and Avrit Funds administered by the University of Cambridge, as well as the Wellcome Trust and British Heart Foundation for their generous support. NR 142 TC 18 Z9 18 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD OCT-NOV PY 2008 VL 98 IS 2-3 SI SI BP 208 EP 218 DI 10.1016/j.pbiomolbio.2008.10.011 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 430CQ UT WOS:000264966800010 PM 19041335 ER PT J AU Killeen, MJ Sabir, IN Grace, AA Huang, CLH AF Killeen, Matthew J. Sabir, Ian N. Grace, Andrew A. Huang, Christopher L. -H. TI Dispersions of repolarization and ventricular arrhythmogenesis: Lessons from animal models SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE Ventricular arrhythmias; Repolarization dispersions; Cardiac electrophysiology; Long QT syndrome ID LONG-QT SYNDROME; TORSADE-DE-POINTES; HYPOKALEMIC MURINE HEART; ACTION-POTENTIAL PROLONGATION; CANINE PURKINJE-FIBERS; SODIUM-CHANNEL BLOCK; EARLY AFTERDEPOLARIZATIONS; K+ CHANNEL; CARDIAC-ARRHYTHMIA; POTASSIUM CHANNELS AB Sudden cardiac death resulting from ventricular arrhythmogenesis is a leading cause of mortality in the developed world, accounting for up to 400,000 deaths per year in the US alone. Within the past forty years we have taken considerable leaps forward in our understanding of the causes and mechanisms underlying cardiac arrhythmias, particularly in the setting of inherited and acquired dysfunctions in ionic currents which constitute human long QT syndrome (LQTS). Impaired repolarization seen in LQTS commonly gives rise to an altered dispersion of repolarization, which is considered to provide the functional substrate necessary for the perpetuation of lethal arrhythmias. This review examines the bases for arrhythmias arising from repolarization heterogeneities and explores the applicability of the genetically amenable moose for the study of arrhythmias arising from such mechanisms. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Killeen, Matthew J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02139 USA. [Killeen, Matthew J.] Harvard Univ, Sch Med, Boston, MA USA. [Sabir, Ian N.; Huang, Christopher L. -H.] Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England. [Grace, Andrew A.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. RP Killeen, MJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02139 USA. EM matthew.killeen@gmail.com FU Physiological Laboratory, University of Cambridge; Harvard Medical School; Massachusetts General Hospital; Wellcome Trust; British Heart Foundation FX MJK is grateful for the support of an Avrith Scholarship from the Physiological Laboratory, University of Cambridge in addition to research fellowships from Harvard Medical School and Massachusetts General Hospital. We also acknowledge support from the Wellcome Trust and the British Heart Foundation. Finally, we Would like to thank Drs Calum Macrae, David Milan, Jeffrey Winterfield (Massachusetts General Hospital) and Dr Glyn Thomas (St. Bartholornews Hospital, London) for helpful discussions. NR 110 TC 21 Z9 22 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD OCT-NOV PY 2008 VL 98 IS 2-3 BP 219 EP 229 DI 10.1016/j.pbiomolbio.2008.10.008 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 430CQ UT WOS:000264966800011 PM 19027779 ER PT J AU Hothi, SS Booth, SW Sabir, IN Killeen, MJ Simpson, F Zhang, YM Grace, AA Huang, CLH AF Hothi, Sandeep S. Booth, Stephen W. Sabir, Ian N. Killeen, Matthew J. Simpson, Fergus Zhang, Yanmin Grace, Andrew A. Huang, Christopher L. -H. TI Arrhythmogenic substrate and its modification by nicorandil in a murine model of long QT type 3 syndrome SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE Arrhythmia; LQT3; Mouse; Nicorandil; Ventricle ID ACTION-POTENTIAL DURATION; T-WAVE ALTERNANS; POTASSIUM CHANNEL OPENERS; VENTRICULAR-FIBRILLATION; TARGETED DISRUPTION; ELECTRICAL RESTITUTION; TRANSMURAL DISPERSION; CALCIUM HOMEOSTASIS; SPATIAL-DISPERSION; GUINEA-PIG AB The gain-of-function Scn5a+/Delta KPQ mutation in the cardiac Na(+) channel Causes human long QT type 3 syndrome (LQT3) associated with ventricular arrhythmogenesis. The K(ATP) channel-opener nicorandil (20 mu M) significantly reduced arrhythmic incidence in Langendorff-perfused Scn5a+/Delta, hearts during programmed electrical stimulation: wild-types (WTs) showed a total absence of arrhythmogenicity. These observations precisely correlated with alterations in recently established criteria for re-entrant excitation reflected in: (1) shortened left-ventricular epicardial but not endocardial monophasic action potential durations at 90% repolarization (APD(90)) that (2) restored transmural repolarization gradients, Delta APD(90). Scn5a+/Delta hearts showed longer epicardial but not endocardial APD(90)s, giving shorter Delta APD(90)s than WT hearts. Nicorandil reduced epicardial APD(90) in both Scn5a+/Delta and WT hearts thereby increasing Delta APD(90). (3) Reduced epicardial critical intervals for re-excitation: Scn5a+/Delta hearts showed greater differences between APD(90) and ventricular effective refractory period than WT hearts that were reduced by nicorandil. (4) Reduced APD(90) alternans. Scn5a+/Delta hearts showed greater epicardial and endocardial alternans than WTs, which increased with pacing rate. Nicorandil reduced these in Scn5a+/Delta hearts to levels indistinguishable from untreated WTs. (5) Flattened restitution curves. Scn5a+/Delta hearts showed larger epicardial and endocardial critical diastolic intervals than WT hearts. Nicorandil decreased these in Scn5a+/Delta, and WT hearts. The presence or absence of arrhythmogenesis in Scn5a+/Delta and WT hearth thus agreed with previously established criteria for re-entrant excitation, and alterations in these precisely correlated with the corresponding antiarrhythmic effects of nicorandil. Together these Findings implicate spatial and temporal re-entrant mechanisms in arrhythmogenesis in LQT3 and their reversal by nicorandil. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Hothi, Sandeep S.; Booth, Stephen W.; Sabir, Ian N.; Huang, Christopher L. -H.] Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England. [Killeen, Matthew J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Killeen, Matthew J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Simpson, Fergus] Univ Edinburgh, Inst Astron, Royal Observ, Scottish Univ Phys Alliance, Edinburgh EH9 3HJ, Midlothian, Scotland. [Zhang, Yanmin] Xi An Jiao Tong Univ, Hosp 1, Dept Paediat, Xian 710061, Shaanxi, Peoples R China. [Zhang, Yanmin; Grace, Andrew A.; Huang, Christopher L. -H.] Univ Cambridge, Dept Biochem, Sect Cardiovasc Biol, Cambridge CB2 1QW, England. RP Hothi, SS (reprint author), Univ Cambridge, Physiol Lab, Downing St, Cambridge CB2 3EG, England. EM ssh26@cam.ac.uk FU Medical Research Council studentship; Murray Edwards College, Cambridge; Wellcome Trust; National Natural Science Foundation of China [30371571, 30672209]; British Heart Foundation; Helen Kirkland Trust; Papworth Hospital, UK; Trinity College, Cambridg FX SSH was supported by a Medical Research Council studentship and thanks Murray Edwards College, Cambridge for an Official Fellowship and College Lectureship in Physiology. SWB was supported by a Wellcome Trust studentship. YZ was Supported by the National Natural Science Foundation of China (YZ; NSFC numbers 30371571 and 30672209). We thank the Wellcome Trust, Medical Research Council, British Heart Foundation, Helen Kirkland Trust, Papworth Hospital, UK. and Trinity College, Cambridge for their generous Support. Sandeep S. Hothi and Stephen W. Booth have contributed equally to this work. NR 53 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD OCT-NOV PY 2008 VL 98 IS 2-3 BP 267 EP 280 DI 10.1016/j.pbiomolbio.2009.01.006 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 430CQ UT WOS:000264966800015 PM 19351517 ER PT J AU Milan, DJ MacRae, CA AF Milan, David J. MacRae, Calum A. TI Zebrafish genetic models for arrhythmia SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE Electrophysiology; Genetics; Zebrafish; Optical mapping ID LONG QT SYNDROME; RIGHT-VENTRICULAR CARDIOMYOPATHY; IN-VIVO; DILATED CARDIOMYOPATHY; CAENORHABDITIS-ELEGANS; CARDIOVASCULAR-SYSTEM; CARDIAC DEVELOPMENT; HEART REGENERATION; HUMAN-DISEASE; MUTATIONS AB Over the last decade the zebrafish has emerged as a major genetic model organism. While stimulated originally by the utility of its transparent embryos for the study of vertebrate organogenesis. the success of the zebrafish was consolidated through multiple genetic screens. sequencing of the fish genome by the Sanger Center, and the advent of extensive genomic resources. In the last few years the potential of the zebrafish for in vivo cell biology, physiology, disease modeling and drug discovery has begun to be realized, This review will highlight work on cardiac electrophysiology, emphasizing the arenas in which the zebrafish complements other in vivo and in vitro models: developmental physiology, large-scale screens, high-throughput disease modeling and drug discovery. Much of this work is at an early stage, and so the focus will be on the general principles, the specific advantages of the zebrafish and on future potential. (C) 2009 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP MacRae, CA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA USA. EM macrae@cvrc.mgh.harvard.edu FU NIGMS NIH HHS [R21 GM075946, R21 GM075946-04] NR 86 TC 23 Z9 25 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD OCT-NOV PY 2008 VL 98 IS 2-3 BP 301 EP 308 DI 10.1016/j.pbiomolbio.2009.01.011 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 430CQ UT WOS:000264966800018 PM 19351520 ER PT J AU Sanches, M Keshavan, MS Brambilla, P Soares, JC AF Sanches, Marsal Keshavan, Matcheri S. Brambilla, Paolo Soares, Jair C. TI Neurodevelopmental basis of bipolar disorder: A critical appraisal SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE bipolar disorder; development; magnetic resonance imaging; mood disorders; neuroimaging ID MINOR PHYSICAL ANOMALIES; MAGNETIC-RESONANCE SPECTROSCOPY; MAJOR DEPRESSIVE DISORDER; DEFICIT HYPERACTIVITY DISORDER; STRUCTURAL BRAIN ABNORMALITIES; MONOZYGOTIC TWINS DISCORDANT; SUBGENUAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; CAVUM-SEPTUM-PELLUCIDUM; PERINATAL RISK-FACTORS AB Neurodevelopmental factors have been implicated in the pathophysiology of mental disorders. However, the evidence regarding their role in bipolar disorder is controversial. We reviewed the pertinent literature searching for evidence regarding a neurodevelopmental origin of bipolar disorder. Findings from clinical, epidemiological, neuroimaging, and post-mortem studies are discussed, as well as the implications of the available data for a better understanding of the mechanisms involved in the genesis of bipolar disorder. While some evidence exists for developmental risk factors in bipolar disorder, further research is needed to determine the precise extent of their contribution to pathogenesis. The timing and course of such developmentally mediated neurobiological alterations also need to be determined. Of particular importance for further study is the possibility that bipolar disorder may be mediated by an abnormal maturation of brain structures involved in affect regulation. (c) 2008 Published by Elsevier Inc. C1 [Brambilla, Paolo; Soares, Jair C.] Univ N Carolina, Dept Psychiat, CERT BD, Chapel Hill, NC 27515 USA. [Sanches, Marsal] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Div Mood & Anxiety Disorders, MOOD CNS Program, San Antonio, TX 78229 USA. [Sanches, Marsal] Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Sanches, Marsal] Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. [Keshavan, Matcheri S.] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI USA. [Brambilla, Paolo] Univ Udine, Sect Psychiat, Dept Pathol & Expt & Clin Med, I-33100 Udine, Italy. [Brambilla, Paolo] IRCCS E Medea, Inst Sci, Udine, Italy. RP Soares, JC (reprint author), Univ N Carolina, Dept Psychiat, CERT BD, Chapel Hill, NC 27515 USA. EM jair_Soares@med.unc.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU UTHSCSA GCRC [M01-RR-01346]; NARSAD; Krus Endowed Chair in Psychiatry (UTHSCSA); Veterans Administration (VA Merit Review); CAPES Foundation (Brazil); [MH 01736]; [MH 068662]; [MH 068766]; [MH 69774]; [MH 64023]; [RR020571] FX This work was partly supported by MH 01736, MH 068662, MH 068766, MH 69774, MH 64023 and RR020571, UTHSCSA GCRC (M01-RR-01346), NARSAD, the Krus Endowed Chair in Psychiatry (UTHSCSA), Veterans Administration (VA Merit Review), NARSAD and CAPES Foundation (Brazil). NR 160 TC 44 Z9 45 U1 6 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD OCT 1 PY 2008 VL 32 IS 7 BP 1617 EP 1627 DI 10.1016/j.pnpbp.2008.04.017 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 357KA UT WOS:000259843500001 PM 18538910 ER PT J AU Haram, KM Peltier, HJ Lu, B Bhasin, M Otu, HH Choy, B Regan, M Libermann, TA Latham, GJ Sanda, MG Arredouani, MS AF Haram, Kerstyn M. Peltier, Heidi J. Lu, Bin Bhasin, Manoj Otu, Hasan H. Choy, Bob Regan, Meredith Libermann, Towia A. Latham, Gary J. Sanda, Martin G. Arredouani, Mohamed S. TI Gene expression profile of mouse prostate tumors reveals dysregulations in major biological processes and identifies potential murine targets for preclinical development of human prostate cancer therapy SO PROSTATE LA English DT Article DE prostate cancer; microarray; TRAMP mice; tumor antigens ID TRANSGENIC MICE; DIFFERENTIAL EXPRESSION; AURORA KINASES; CYCLIN-A; MODEL; PROGRESSION; SOX4; TUBULIN; CELLS; AMPLIFICATION AB BACKGROUND. Translation of preclinical studies into effective human cancer therapy is hampered by the lack of defined molecular expression patterns in mouse models that correspond to the human counterpart. We sought to generate an open source TRAMP mouse microarray dataset and to use this array to identify differentially expressed genes from human prostate cancer (PCa) that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. METHODS. We performed microarrays on total RNA extracted and amplified from eight TRAMP tumors and nine normal prostates. A subset of differentially expressed genes was validated by QRT-PCR. Differentially expressed TRAMP genes were analyzed for concordant expression in publicly available human prostate array datasets and a subset of resulting genes was analyzed by QRT-PCR. RESULTS. Cross-referencing differentially expressed TRAMP genes to public human prostate array datasets revealed 66 genes with concordant expression in mouse and human PCa; 56 between metastases and normal and 10 between primary tumor and normal tissues. Of these 10 genes, two, Sox4 and Tubb2a, were validated by QRT-PCR. Our analysis also revealed various dysregulations in major biologic pathways in the TRAMP prostates. CONCLUSIONS. We report a TRAMP microarray dataset of which a gene subset was validated by QRT-PCR with expression patterns consistent with previous gene-specific TRAMP studies. Concordance analysis between TRAMP and human PCa associated genes supports the utility of the model and suggests several novel molecular targets for preclinical therapy. C1 [Haram, Kerstyn M.; Lu, Bin; Sanda, Martin G.; Arredouani, Mohamed S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Urol, Boston, MA 02115 USA. [Peltier, Heidi J.; Latham, Gary J.] Asuragen Inc, Austin, TX USA. [Bhasin, Manoj; Otu, Hasan H.; Choy, Bob; Libermann, Towia A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Genom Ctr, Boston, MA 02115 USA. [Regan, Meredith] Harvard Univ, Sch Med, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sanda, MG (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Urol, 77 Ave Louis Pasteur,Him-1047, Boston, MA 02115 USA. EM msanda@bidmc.harvard.edu RI Libermann, Towia/F-9866-2010; Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; OI Libermann, Towia/0000-0002-4006-8179; Otu, Hasan/0000-0002-9253-8152 FU NCI NIH HHS [U01 CA11391]; NIDDK NIH HHS [P50 DK065313] NR 55 TC 21 Z9 21 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD OCT 1 PY 2008 VL 68 IS 14 BP 1517 EP 1530 DI 10.1002/pros.20803 PG 14 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 354QQ UT WOS:000259654500005 PM 18668517 ER PT J AU Sher, DJ Oh, WK Jacobus, S Regan, MM Lee, GS Mantzoros, C AF Sher, David J. Oh, William K. Jacobus, Susanna Regan, Meredith M. Lee, Gwo-Shu Mantzoros, Christos TI Relationship between serum adiponectin and prostate cancer grade SO PROSTATE LA English DT Article DE prostate cancer; adiponectin; Gleason score ID RADICAL PROSTATECTOMY; PATHOLOGICAL VARIABLES; ENDOMETRIAL CANCER; RADIATION-THERAPY; NEEDLE-BIOPSY; OBESITY; RISK; MEN; ASSOCIATION; RECURRENCE AB BACKGROUND. Obesity is associated with prostate cancer (PCA) grade, but the mechanism behind this relationship is not understood. Adiponectin is an adipokine that has been linked with the development of hormonally sensitive carcinomas, including prostate cancer. We evaluated the relationship between serum adiponectin and Gleason score (GS) in a prospective series of patients seen in a single institution. METHODS. Localized PCA patients evaluated at Dana-Farber Cancer Institute between 2001 and 2005 who enrolled in a prospective serum banking protocol were eligible for this study. Patients with prior hormonal therapy and/or metastatic disease were excluded. High-grade disease was defined as biopsy or radical prostatectomy (RP) GS of 7 or higher. Logistic regression models were used to assess the relationship between high-grade disease and adiponectin levels while adjusting for other potential prognostic variables. RESULTS. There were 539 patients included in this study, of whom 199 had undergone RP. Median age was 60 years. Median PSA was 5.1 ng/dl. Biopsy GS of 7 or higher was seen in 46.9% of patients. For biopsy GS, higher PSA, older age, and higher BMI were significantly associated with increased odds of GS 7 or higher, but adiponectin was not. In men undergoing RP, there was a significant inverse relationship between pathologic GS and adiponectin dichotomized at the median, due to a significantly higher rate of upgrading in patients with lower adiponectin (P = 0.014). CONCLUSIONS. Although there was no association between biopsy GS and adiponectin, in patients who had undergone RP, lower adiponectin was independently associated with high-grade prostate cancer. C1 [Oh, William K.; Lee, Gwo-Shu] Dana Farber Canc Inst, Lank Ctr Gertitourinary Oncol, Dept Med Oncol, Boston, MA 02115 USA. [Sher, David J.] Harvard Univ, Radiat Oncol Program, Boston, MA 02115 USA. [Jacobus, Susanna; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Mantzoros, Christos] Beth Israel Deaconess Med Sch, Dept Med, Boston, MA USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Gertitourinary Oncol, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU Bing Sound Wong Fund; Nehemias Gorin Foundation FX This study was supported by Bing Sound Wong Fund for Prostate Cancer Research and the Nehemias Gorin Foundation (both to WKO). NR 24 TC 26 Z9 27 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD OCT 1 PY 2008 VL 68 IS 14 BP 1592 EP 1598 DI 10.1002/pros.20823 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 354QQ UT WOS:000259654500012 PM 18646046 ER PT J AU Ramachandran, N Anderson, KS Raphael, JV Hainsworth, E Sibani, S Montor, WR Pacek, M Wong, J Eljanne, M Sanda, MG Hu, YH Logvinenko, T LaBaer, J AF Ramachandran, Niroshan Anderson, Karen S. Raphael, Jacob V. Hainsworth, Eugenie Sibani, Sahar Montor, Wagner R. Pacek, Marcin Wong, Jessica Eljanne, Mariam Sanda, Martin G. Hu, Yanhui Logvinenko, Tanya LaBaer, Joshua TI Tracking humoral responses using self assembling protein microarrays SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE Biomarkers; Functional Proteomics; High-throughput; Immunoassay; Protein microarray ID AUTOIMMUNE-DISEASES; OVARIAN-CANCER; MARKERS; ARRAYS; GENERATION; IMMUNITY; IMMOBILIZATION; AUTOANTIBODIES; ANTIGENS; MEMORY AB The humoral immune response is a highly specific and adaptive sensor for changes in the body's protein milieu, which responds to novel structures of both foreign and self antigens. Although Igs represent a major component of human serum and are vital to survival, little is known about the response specificity and determinants that govern the human immunome. Historically, antigen-specific humoral immunity has been investigated using individually produced and purified target proteins, a labor-intensive process that has limited the number of antigens that have been studied. Here, we present the development of methods for applying self-assembling protein microarrays and a related method for producing 96-well formatted macroarrays for monitoring the humoral response at the proteome scale. Using plasmids encoding full-length cDNAs for over 850 human proteins and 1700 pathogen proteins, we demonstrate that these microarrays are highly sensitive, specific, reproducible, and can simultaneously measure immunity to thousands of proteins without a priori protein purification. Using this approach, we demonstrate the detection of humoral immunity to known and novel self-antigens, cancer antigens, autoimmune antigens, as well as pathogen-derived antigens. This represents a powerful and versatile tool for monitoring the immunome in health and disease. C1 [Ramachandran, Niroshan; Raphael, Jacob V.; Hainsworth, Eugenie; Sibani, Sahar; Montor, Wagner R.; Pacek, Marcin; Hu, Yanhui; LaBaer, Joshua] Harvard Univ, Sch Med, Harvard Inst Prote, Cambridge, MA 02141 USA. [Anderson, Karen S.; Wong, Jessica] Harvard Univ, Sch Med, Canc Vaccine Ctr, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA USA. [Hainsworth, Eugenie] Harvard Univ, Sch Med, Technol & Engn Ctr, Boston, MA USA. [Eljanne, Mariam; Sanda, Martin G.] Beth Israel Deaconess Med Ctr, Div Urol, Boston, MA 02215 USA. [Logvinenko, Tanya] Tufts Univ New England Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. RP LaBaer, J (reprint author), Harvard Univ, Sch Med, Harvard Inst Prote, 320 Charles St, Cambridge, MA 02141 USA. EM joshua_labaer@hms.harvard.edu RI Montor, Wagner/J-2568-2012; Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 OI Montor, Wagner/0000-0003-3746-9366; FU Early Detection Research Network (EDRN, NCI) [5U01CA117374-02]; National Institute of Allergy and Infectious Diseases (NIAID) [HHSN266200400053C]; Juvenile Diabetes Research Foundation [17-2007-1045] FX We thank Janice Williamson and Mauricio Fernandez from the Harvard Institute of Proteomics, Harvard Medical School for their support. We thank David Lane and Alison Sparks (University of Dundee) for the p53 antibodies. We thank Dr. Andrew Godwin at I-ox Chase Cancer Center for providing us with serum from breast cancer patients. We thank Drs. Stephen Lory, Dennis Kasper, and Gerald Beltz from the Harvard Medical School for providing serum from patients with infected with P. aeruginosa, and mice infected with F. tularensis. This study was supported by research grants from the Early Detection Research Network (EDRN, NCI, Grant 5U01CA117374-02), the National Institute of Allergy and Infectious Diseases (NIAID, Contract HHSN266200400053C) and the Juvenile Diabetes Research Foundation (Grant 17-2007-1045). NR 39 TC 31 Z9 32 U1 0 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1862-8346 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD OCT PY 2008 VL 2 IS 10-11 BP 1518 EP 1527 DI 10.1002/prca.200800034 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 362PG UT WOS:000260209000014 PM 21136799 ER PT J AU Baldessarini, R Henk, H Sklar, A Chang, J Leahy, L AF Baldessarini, Ross Henk, Henry Sklar, Ami Chang, Jane Leahy, Leslie TI Psychotropic medications for patients with bipolar disorder in the United States: Polytherapy and adherence SO PSYCHIATRIC SERVICES LA English DT Article; Proceedings Paper CT 160th Annual Meeting of the American-Psychiatric-Association CY MAY 19-24, 2007 CL San Diego, CA SP Amer Psychiat Assoc ID UNIPOLAR DEPRESSION; I DISORDER; MORBIDITY; LITHIUM; RISK; MORTALITY; THERAPY; HISTORY AB Objective: Because treatments for bipolar disorder include a growing number of psychotropic agents, the authors evaluated psychotropic polytherapy and adherence to treatment among U. S. patients with bipolar disorder. Methods: National health plan claims data (2000-2004) were used to identify patients diagnosed as having bipolar disorder who had continuous benefits and had not been prescribed medication for bipolar disorder for six months or more. The study compared drugs dispensed to these patients initially and at one year and characterized patients who were adherent to mood-stabilizers. Results: A total of 7,406 patients had a bipolar disorder: bipolar I (55%), bipolar II (15%), or bipolar disorder not otherwise specified (30%). Women represented 57% of the sample; mean +/- SD age was 35.4 +/- 12.4 years. Initial prescription fills involved one psychotropic agent in 67% of patients, and two or more psychotropics (polytherapy) in 33%. Initial prescription drug selections involved: antidepressants > anticonvulsants >= antipsychotics > sedatives > lithium; initial mood stabilizer use ranked: valproate > lithium > carbamazepine or oxcarbazepine > lamotrigine; antipsychotics ranked: olanzapine > quetiapine >= risperidone > ziprasidone > aripiprazole > clozapine. Rankings were similar at one year, when only 31% of patients received monotherapy (a 2.2-fold decline), 32% received polytherapy, and 37% received no psychotropics. Initially patients received 1.42 psychotropic drugs per person; at one year, patients received 175, and at both times polytherapy was less likely with lithium than with anticonvulsants. In multivariate modeling, one-year mood stabilizer use was greater with the following: older age, type of mood stabilizer (lamotrigine > valproate > carbamazepine or oxcarbazepine > lithium) and was associated with more psychiatric office and emergency visits, clinician type (more common with psychiatrists than with primary care physicians), and nonuse of off-label anticonvulsants. Conclusions: Polytherapy was used by one-third of patients initially and at one year, antidepressant use was highly prevalent initially and later, but lack of treatment was prevalent at one year. Plausible clinical and treatment factors were associated with sustained mood stabilizer adherence. C1 [Baldessarini, Ross] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Henk, Henry; Sklar, Ami] I3 Innovus, Dept Hlth Econ & Outcomes Res, Eden Prairie, MN USA. [Chang, Jane; Leahy, Leslie] Novartis Corp, Dept Res, E Hanover, NJ USA. RP Baldessarini, R (reprint author), Massachusetts Gen Hosp, McLean Div, 115 Mill St, Belmont, MA 02478 USA. EM rjb@mclean.org NR 33 TC 92 Z9 94 U1 1 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD OCT PY 2008 VL 59 IS 10 BP 1175 EP 1183 DI 10.1176/appi.ps.59.10.1175 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 355IV UT WOS:000259703500016 PM 18832504 ER PT J AU Zwahlen, D Hagenbuch, N Carley, MI Recklitis, CJ Buchi, S AF Zwahlen, Diana Hagenbuch, Niels Carley, Margaret I. Recklitis, Christopher J. Buchi, Stefan TI Screening cancer patients' families with the distress thermometer (DT): a validation study SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; distress thermometer; distress; family ID MARROW TRANSPLANT PATIENTS; OF-THE-LITERATURE; PSYCHOLOGICAL DISTRESS; HOSPITAL ANXIETY; DEPRESSION SCALE; DIAGNOSTIC-TESTS; PROSTATE-CANCER; INFORMAL CARERS; GERMAN VERSION; BREAST-CANCER AB Although family members of cancer patients are at great risk of experiencing psychological distress, clinical tools to assist with recognizing and intervening with appropriate psychosocial care are sparse. This study reports on the first validation of the distress thermometer (DT) as a screening instrument for symptoms of depression and anxiety in family members of cancer patients. The DT was administered with the Hospital Anxiety and Depression Scale (HADS) in a sample of 321 family members. Receiver operating characteristics (ROC) demonstrated that the DT has good diagnostic utility relative to the HADS (area under the curve = 0.88 relative to the HADS anxiety scale; 0.84 relative to the HADS depression scale, respectively). The ROC curves indicate that using a cut-off of 4/5 maximizes sensitivity (86.2% HADS anxiety scale; 88.2% HADS depression scale) and specificity (71.2% HADS anxiety scale; 67.6% HADS depression scale); however, the alternative lower cut-off of 3/4 increases sensitivity (94.1% for both scales) and hence reduces the risk of missing distressed family members (specificity is 62.9% for HADS anxiety scale; 59.1% for HADS depression scale). The results offer validation of the DT for screening family members of cancer patients and support its use for clinical assessment. Distress screening with DT for family members of cancer patients is a promising and efficient approach to integrating family members in the program of care and provides the first step toward meeting their unmet needs with referral for supportive services. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Zwahlen, Diana; Hagenbuch, Niels; Buchi, Stefan] Univ Zurich Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland. [Recklitis, Christopher J.] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. RP Buchi, S (reprint author), Univ Zurich Hosp, Dept Psychiat, Ramistr 100, CH-8091 Zurich, Switzerland. EM Stefan.Buechi@usz.ch FU Zurich Cancer League FX This work was supported by the Zurich Cancer League (Krebsliga Zurich, www.krebsliga-zh.ch). NR 55 TC 44 Z9 45 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD OCT PY 2008 VL 17 IS 10 BP 959 EP 966 DI 10.1002/pon.1320 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 364QU UT WOS:000260351000001 PM 18203146 ER PT J AU Pekary, AE Sattin, A Blood, J Furst, S AF Pekary, Albert Eugene Sattin, Albert Blood, James Furst, Stephanie TI TRH and TRH-like peptide expression in rat following episodic or continuous corticosterone SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Chronic corticosterone; Thyrotropin-releasing; hormone; Limbic system; Depression ID THYROTROPIN-RELEASING-HORMONE; CENTRAL-NERVOUS-SYSTEM; PITUITARY-ADRENAL FUNCTION; GLUCOCORTICOIDS STIMULATE; PROLONGED TREATMENT; RAPID MODULATION; MOOD DISORDERS; IN-VITRO; BRAIN; DEPRESSION AB Sustained abnormalities of glucocorticoid Levels have been associated with neuropsychiatric illnesses such as major depression, posttraumatic stress disorder (PTSD), panic disorder, and obsessive compulsive disorder. The pathophysiological effects of glucocorticoids may depend not only on the amount of glucocorticoid exposure but also on its temporal pattern, since it is well established that hormone receptors are down-regulated by continuously elevated cognate hormones. We have previously reported that TRH (pGLu-His-Pro-NH2) and TRH-like peptides (pGlu-X-Pro-NH2) have endogenous antidepressant-like properties and mediate or modulate the acute effects of a single i.p. injection of high dose corticosterone (CORT) in rats. For these reasons, two accepted methods for inducing chronic hyperglucocorticoidemia have been compared for their effects on brain and peripheral tissue Levels of TRH and TRH-like peptides in mate, 250 g, Sprague-Dawley rats: (1) the dosing effect of CORT hemisuccinate in drinking water, and (2) s.c. slow-release pellets. Overall, there were 93% more significant changes in TRH and TRH-Like peptide Levels in brain and 111% more in peripheral tissues of those rats ingesting various doses of CORT in drinking water compared to those with 1-3 s.c. pellets. We conclude that providing rats with CORT in drinking water is a convenient model for the pathophysiological effects of hyperglucocorticoidemia in rodents. Published by Elsevier Ltd. C1 [Pekary, Albert Eugene; Sattin, Albert; Blood, James; Furst, Stephanie] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. [Sattin, Albert] VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA 90073 USA. [Pekary, Albert Eugene] VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res, Los Angeles, CA 90073 USA. [Sattin, Albert] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. [Sattin, Albert] Univ Calif Los Angeles, Res Inst, Los Angeles, CA 90073 USA. [Pekary, Albert Eugene] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Pekary, AE (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, Bldg 114,Room 229,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Eugene.Pekary@va.gov FU Department of Veterans Affairs FX This work was supported by the Department of Veterans Affairs (A.E.P. and A.S.). The authors thank Fredericka Martin, Ph.D., for suggesting Experiment 4. NR 59 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD OCT PY 2008 VL 33 IS 9 BP 1183 EP 1197 DI 10.1016/j.psyneuen.2008.06.001 PG 15 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 361XA UT WOS:000260159800002 PM 18657370 ER PT J AU Naliboff, BD Waters, AM Labus, JS Kilpatrick, L Craske, MG Chang, L Negoro, H Ibrahimovic, H Mayer, EA Ornitz, E AF Naliboff, Bruce D. Waters, Allison M. Labus, Jennifer S. Kilpatrick, Lisa Craske, Michelle G. Chang, Lin Negoro, Hideki Ibrahimovic, Hana Mayer, Emeran A. Ornitz, Edward TI Increased Acoustic Startle Responses in IBS Patients During Abdominal and Nonabdominal Threat SO PSYCHOSOMATIC MEDICINE LA English DT Article DE irritable bowel syndrome; functional bowel disorders; acoustic startle response; fear-potentiated startle ID IRRITABLE-BOWEL-SYNDROME; FEAR-POTENTIATED STARTLE; VISCERAL STIMULI; ANXIETY; PAIN; PERCEPTION; DISORDERS; SEX; SENSITIVITY; INHIBITION AB Background and Aims: Visceral hypersensitivity and symptom severity in Irritable Bowel Syndrome (IBS) are both exacerbated by stress. The eye-blink startle response represents a noninvasive measure of central defensive responding. Evidence for central hyperexcitability was studied in IBS patients by examining potentiation of the startle reflex to a nociceptive threat. Methods: Acoustic startle responses were examined in fernale IBS patients (n = 42) and healthy controls (n = 22) during cued periods in which an aversive abdominal or biceps stimulation was impossible (safe), possible (imminent threat) or anticipated (period just before the imminent threat), and during a threatening context (muscle stimulation pads attached but no cues for stimulation). Results: Both groups showed potentiation of startle responses during the imminent threat condition compared with both the anticipation and safe conditions. Compared With controls, IBS subjects showed significantly larger startle responses during anticipation and imminent threat conditions after receiving an initial aversive stimulation. There were no group differences during the context threat manipulation. Moreover, in IBS patients but not controls, higher neuroticism was associated with larger startle responses during safe and anticipation conditions but not imminent threat, whereas anxiety symptoms were negatively associated with startle magnitude during imminent threat. Conclusions: Female IBS patients show increased startle responses to threat of aversive stimulation at both abdominal and nonabdominal sites compared with controls. The data represent the first demonstration of altered threat potentiated startle in a functional pain condition and provide support for the use of these paradigms in further evaluation of affective mechanisms in these disorders. C1 [Naliboff, Bruce D.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Los Angeles, CA 90073 USA. [Chang, Lin; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. [Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. [Naliboff, Bruce D.; Labus, Jennifer S.; Kilpatrick, Lisa; Craske, Michelle G.; Mayer, Emeran A.; Ornitz, Edward] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. [Naliboff, Bruce D.; Ibrahimovic, Hana] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Waters, Allison M.] Griffith Univ, Sch Psychol, Nathan, Qld 4111, Australia. [Negoro, Hideki] Nara Med Univ, Dept Psychiat, Nara, Japan. [Mayer, Emeran A.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Naliboff, BD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM naliboff@ucla.edu RI Kilpatrick, Lisa/E-6995-2015; OI Waters, Allison/0000-0003-2453-793X FU NIH [NR007768, P50 DK64539, R24 AT002681]; VA Medical Research; Virginia Friedhofer Charitable Trust FX Supported in part by NIH Grants NR007768 (to B.N.), P50 DK64539 (to E.A.M.), R24 AT002681 (to E.A.M.), VA Medical Research (to B.N.), and a gift from the Virginia Friedhofer Charitable Trust (to E.O.). NR 37 TC 27 Z9 27 U1 9 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD OCT PY 2008 VL 70 IS 8 BP 920 EP 927 DI 10.1097/PSY.0b013e318186d858 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 365JF UT WOS:000260401100012 PM 18842745 ER PT J AU Ogrinc, G Mooney, SE Estrada, C Foster, T Goldmann, D Hall, LW Huizinga, MM Liu, SK Mills, P Neily, J Nelson, W Pronovost, PJ Provost, L Rubenstein, LV Speroff, T Splaine, M Thomson, R Tomolo, AM Watts, B AF Ogrinc, G. Mooney, S. E. Estrada, C. Foster, T. Goldmann, D. Hall, L. W. Huizinga, M. M. Liu, S. K. Mills, P. Neily, J. Nelson, W. Pronovost, P. J. Provost, L. Rubenstein, L. V. Speroff, T. Splaine, M. Thomson, R. Tomolo, A. M. Watts, B. TI The SQUIRE (Standards for QUality Improvement Reporting Excellence) guidelines for quality improvement reporting: explanation and elaboration SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID INTENSIVE-CARE-UNIT; RANDOMIZED CONTROLLED-TRIALS; BLOOD-STREAM INFECTIONS; RAPID RESPONSE TEAM; DECREASES CARDIAC-ARREST; CONSORT STATEMENT; OUTCOMES; IMPLEMENTATION; PROGRAM; PROJECT AB As the science of quality improvement in health care advances, the importance of sharing its accomplishments through the published literature increases. Current reporting of improvement work in health care varies widely in both content and quality. It is against this backdrop that a group of stakeholders from a variety of disciplines has created the Standards for QUality Improvement Reporting Excellence, which we refer to as the SQUIRE publication guidelines or SQUIRE statement. The SQUIRE statement consists of a checklist of 19 items that authors need to consider when writing articles that describe formal studies of quality improvement. Most of the items in the checklist are common to all scientific reporting, but virtually all of them have been modified to reflect the unique nature of medical improvement work. This "Explanation and Elaboration'' document (E & E) is a companion to the SQUIRE statement. For each item in the SQUIRE guidelines the E & E document provides one or two examples from the published improvement literature, followed by an analysis of the ways in which the example expresses the intent of the guideline item. As with the E & E documents created to accompany other biomedical publication guidelines, the purpose of the SQUIRE E & E document is to assist authors along the path from completion of a quality improvement project to its publication. The SQUIRE statement itself, this E & E document, and additional information about reporting improvement work can be found at http://www.squire-statement.org. C1 [Ogrinc, G.] Dartmouth Inst Hlth Policy & Clin Practice, Qual Literature Program, Hanover, NH USA. [Ogrinc, G.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Off Res & Innovat Med Educ, Hanover, NH 03756 USA. [Ogrinc, G.] White River Junct VA Hosp, White River Jct, VT USA. [Mooney, S. E.] Alice Peck Day Mem Hosp, Lebanon, NH USA. [Estrada, C.] Univ Alabama, VA Natl Qual Scholars Program, Birmingham VA Med Ctr, Birmingham, AL USA. [Foster, T.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Goldmann, D.] Harvard Univ, Sch Med, IHI, Boston, MA USA. [Hall, L. W.] Univ Missouri, Sch Med, Univ Missouri Hlth Care, Columbia, MO USA. [Huizinga, M. M.] Vanderbilt Univ, Med Ctr, Nashville, TN 37212 USA. [Liu, S. K.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. [Liu, S. K.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA. [Mills, P.] VA Natl Ctr Patient Safety Field Off, White River Jct, VT USA. [Mills, P.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Neily, J.] Field Off VHAs Natl Ctr Patient Safety, White River Jct, VT USA. [Nelson, W.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Inst Hlth Policy & Clin Practice, Rural Eth Initiat,Dartmouth Med Sch, Hanover, NH 03756 USA. [Pronovost, P. J.] Johns Hopkins Univ, Sch Med, Ctr Innovat Qual Patient Care, Dept Anesthesiol & Crit Car,Qual & Safety Res Grp, Baltimore, MD USA. [Pronovost, P. J.] Johns Hopkins Univ, Sch Med, Ctr Innovat Qual Patient Care, Qual & Safety Res Grp,Dep Surg, Baltimore, MD USA. [Pronovost, P. J.] Johns Hopkins Univ, Qual & Safety Res Grp, Ctr Innovat Qual Patient Care, Dep Hlth Policy & Management,Sch Med, Baltimore, MD USA. [Provost, L.] Associates Proc Improvement, Austin, TX USA. [Rubenstein, L. V.] VA Greater Angeles, North Hills, CA USA. [Rubenstein, L. V.] Univ Calif Los Angeles, VA HSRD Ctr Excellence Study Healthcare Provider, RAND Corp, VA Greater Los Angeles Sepulveda, North Hills, CA USA. [Speroff, T.] Vanderbilt Univ, Sch Med, VA Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. [Splaine, M.] Dartmouth Coll, Dartmouth Inst Hlth Policy & Clin Practice, VA Natl Qual Scholars Fellowship Program, Hitchcock Med Ctr,Dartmouth Med Sch, Hanover, NH 03756 USA. [Thomson, R.] Newcastle Univ, Sch Med, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Tomolo, A. M.] Case Western Reserve Univ, SOM, Emergency Dept, Louis Stokes Cleveland DVAMC, Cleveland, OH 44106 USA. [Watts, B.] Louis Stokes Cleveland VA Med Ctr, Dept Med, Cleveland, OH USA. RP Ogrinc, G (reprint author), Dartmouth Med Sch, 215 N Main St, White River Jct, VT 05009 USA. EM greg.ogrinc@med.va.gov NR 46 TC 153 Z9 153 U1 1 U2 8 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD OCT PY 2008 VL 17 SU 1 BP 13 EP 32 DI 10.1136/qshc.2008.029058 PG 20 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 356WM UT WOS:000259808300004 ER PT J AU Kaewlai, R Avery, LL Asrani, AV Novelline, RA AF Kaewlai, Rathachai Avery, Laura L. Asrani, Ashwin V. Novelline, Robert A. TI Multidetector CT of Blunt Thoracic Trauma SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 93rd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 25-30, 2007 CL Chicago, IL SP Radiol Soc N Amer ID CHEST TRAUMA; FLAIL CHEST; PULMONARY CONTUSION; RIB FRACTURES; INJURY; MANAGEMENT; MORTALITY; DIAGNOSIS; RUPTURE; HEART AB Thoracic injuries are significant causes of morbidity and mortality in trauma patients. These injuries account for approximately 25% of trauma- related deaths in the United States, second only to head injuries. Radiologic imaging plays an important role in the diagnosis and management of blunt chest trauma. In addition to conventional radiography, multidetector computed tomography (CT) is increasingly being used, since it can quickly and accurately help diagnose a wide variety of injuries in trauma patients. Furthermore, multiplanar and volumetric reformatted CT images provide improved visualization of injuries, increased understanding of trauma- related diseases, and enhanced communication between the radiologist and the referring clinician. (C) RSNA, 2008 center dot radiographics.rsnajnls.org C1 [Kaewlai, Rathachai; Avery, Laura L.; Asrani, Ashwin V.; Novelline, Robert A.] Massachusetts Gen Hosp, Div Emergency Radiol, Dept Radiol, Boston, MA 02114 USA. RP Kaewlai, R (reprint author), Massachusetts Gen Hosp, Div Emergency Radiol, Dept Radiol, 55 Fruit St,FND 210, Boston, MA 02114 USA. EM rathachai@gmail.com OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 50 TC 32 Z9 39 U1 1 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2008 VL 28 IS 6 BP 1555 EP 1570 DI 10.1148/rg.286085510 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 362WG UT WOS:000260227300003 PM 18936021 ER PT J AU Kaewlai, R Avery, LL Asrani, AV Abujudeh, HH Sacknoff, R Novelline, RA AF Kaewlai, Rathachai Avery, Laura L. Asrani, Ashwin V. Abujudeh, Hani H. Sacknoff, Richard Novelline, Robert A. TI Multidetector CT of Carpal Injuries: Anatomy, Fractures, and Fracture-Dislocations SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 93rd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 25-30, 2007 CL Chicago, IL SP Radiol Soc N Amer ID OCCULT SCAPHOID FRACTURES; PERILUNATE DISLOCATIONS; COMPUTED-TOMOGRAPHY; TRAPEZIAL RIDGE; BONE-FRACTURES; WRIST; INSTABILITY; VASCULARITY; DIAGNOSIS; PATTERNS AB Fractures and dislocations of the carpal bones are more common in young active patients. These injuries can lead to pain, dysfunction, and loss of productivity. Conventional radiography remains the primary imaging modality for evaluation of suspected carpal fractures and dislocations. However, multidetector computed tomography (CT) is playing an increasingly important role, especially in the following situations: (a) when results from initial radiographs are negative in patients with suspected carpal fractures, (b) when initial radiographic findings are indeterminate, and (c) when knowledge of the extent of carpal fractures or dislocations is required before surgical treatment. The advantages of multidetector CT include quick and accurate diagnosis with availability in most emergency centers. Multidetector CT can easily display the extent of carpal fractures and dislocations, often depicting fractures that are occult at radiography. In addition, with multiplanar (two-dimensional) and volumetric (three-dimensional) reformation, pathologic conditions and anatomic relationships are better perceived. This information can be easily conveyed to orthopedic and trauma surgeons and can be crucial for surgical treatment and planning. (C) RSNA, 2008 center dot radiographics. rsnajnls. org C1 [Kaewlai, Rathachai] Massachusetts Gen Hosp, Div Emergency Radiol, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kaewlai, R (reprint author), Massachusetts Gen Hosp, Div Emergency Radiol, Dept Radiol, 55 Fruit St,FND 210, Boston, MA 02114 USA. EM rathachai@gmail.com OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 40 TC 21 Z9 24 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2008 VL 28 IS 6 BP 1771 EP 1784 DI 10.1148/rg.286085511 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 362WG UT WOS:000260227300017 PM 18936035 ER PT J AU Sarwar, A Rieber, J Mooyaart, EAQ Seneviratne, SK Houser, SL Bamberg, F Raffel, OC Gupta, R Kalra, MK Pien, H Lee, H Brady, TJ Hoffmann, U AF Sarwar, Ammar Rieber, Johannes Mooyaart, Eline A. Q. Seneviratne, Sujith K. Houser, Stuart L. Bamberg, Fabian Raffel, O. Christopher Gupta, Rajiv Kalra, Mannudeep K. Pien, Homer Lee, Hang Brady, Thomas J. Hoffmann, Udo TI Calcified plaque: Measurement of area at thin-section flat-panel CT and 64-section multidetector CT and comparison with histopathologic findings SO RADIOLOGY LA English DT Article ID SPIRAL COMPUTED-TOMOGRAPHY; CORONARY-ARTERY-DISEASE; ATHEROSCLEROTIC PLAQUE; ROW CT; ANGIOGRAPHY; MORPHOLOGY; CALCIUM; LESIONS; QUANTIFICATION; CALCIFICATION AB The purpose of this study was to assess the blooming artifacts in ex vivo coronary arteries at multidetector computed tomography (CT) and flat-panel-volume CT by comparing measured areas of calcified plaque with respect to the reference standard of histopathologic findings. Three ex vivo hearts were scanned with multidetector CT and flat-panel-volume CT after institutional review board approval. The area of calcified plaque was measured at histopathologic examination, multidetector CT, and flat-panel volume CT. The plaque area was overestimated at multidetector CT by 400% (4.61/1.15) on average, and the predicted difference between the measurements was significant (3.46 mm(2), P = .018). The average overestimation of plaque area at flat-panel-volume CT was twofold (214% [2.18/1.02]), and the predicted difference was smaller (1.16 mm(2), P = .08). The extent of the blooming artifact in visualizing calcified coronary plaque is reduced by using flat-panel-volume CT. (c) RSNA, 2008. C1 [Sarwar, Ammar; Rieber, Johannes; Mooyaart, Eline A. Q.; Seneviratne, Sujith K.; Houser, Stuart L.; Bamberg, Fabian; Raffel, O. Christopher; Gupta, Rajiv; Kalra, Mannudeep K.; Pien, Homer; Lee, Hang; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,4th Floor,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org NR 24 TC 33 Z9 35 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2008 VL 249 IS 1 BP 301 EP 306 DI 10.1148/radiol.2483072003 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 352NY UT WOS:000259505200036 PM 18710960 ER PT J AU Greathouse, KL Cook, JD Lin, K Davis, BJ Berry, TD Bredfeldt, TG Walker, CL AF Greathouse, K. L. Cook, J. D. Lin, K. Davis, B. J. Berry, T. D. Bredfeldt, T. G. Walker, C. L. TI Identification of Uterine Leiomyoma Genes Developmentally Reprogrammed by Neonatal Exposure to Diethylstilbestrol SO REPRODUCTIVE SCIENCES LA English DT Article DE Uterine leiomyoma; developmental reprogramming; diethylstilbestrol; gene expression ID TYPE-2 IODOTHYRONINE DEIODINASE; BONE MORPHOGENETIC PROTEIN-3; CALBINDIN-D-9K MESSENGER-RNA; RAT UTERUS; IN-UTERO; MATRIX METALLOPROTEINASES; EXPRESSION; ESTROGEN; CANCER; ADENOCARCINOMA AB Environmental exposures during development can alter susceptibility later in life to adult diseases including uterine leiomyoma, a phenomenon termed developmental reprogramming. The goal of this study was to identify genes developmentally reprogrammed by diethylstilbestrol (DES) and aberrantly expressed in leiomyomas. Transcriptional profiling identified 171 genes differentially expressed in leiomyomas relative to normal myometrium, Of which 6/18 genes with putative estrogen responsive elements and confirmed to be estrogen-responsive in neonatal uteri were reprogrammed by neonatal DES exposure. Calbindin D9k and Dio2, normally induced by estrogen, exhibited elevated expression in DES-exposed animals during both phases of the estrus cycle. Gdf10, CarS, Gria2, and Mmp3, genes normally repressed by estrogen, exhibited elevated expression in DES-exposed animals during the proliferative phase, when estrogen is highest. These data demonstrate that neonatal DES exposure causes reprogramming of estrogen-responsive genes expressed in uterine leiomyomas, leading to over-expression of these genes in the myometrium of exposed animals prior to the onset of tumorigenesis. C1 [Greathouse, K. L.; Lin, K.; Berry, T. D.; Bredfeldt, T. G.; Walker, C. L.] MD Anderson Canc Ctr, Sci Pk Res Div, Dept Carcinogenesis, Smithville, TX USA. [Cook, J. D.] Dana Farber Canc Inst, Boston, MA USA. [Davis, B. J.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Davis, B. J.] NIEHS, Res Triangle Pk, NC USA. RP Walker, CL (reprint author), 1808 Pk Rd 1C,POB 389, Smithville, TX 78957 USA. EM cwalker@odin.mdacc.tmc.edu FU National Institutes of Health [HD046282]; NIEHS [ES008263, ES007784] FX This work was done at the MD Anderson Cancer Center, Science Park Research Division, Smithville, TX. This work was supported by National Institutes of Health Grants HD046282 and NIEHS Grants ES008263 and ES007784. NR 53 TC 30 Z9 30 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD OCT PY 2008 VL 15 IS 8 BP 765 EP 778 DI 10.1177/1933719108322440 PG 14 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 366TM UT WOS:000260506300004 PM 19017814 ER PT J AU Prodhan, P Dela Rosa, RS Shubina, M Haver, KE Matthews, BD Buck, S Kacmarek, RM Noviski, NN AF Prodhan, Parthak Dela Rosa, Reynaldo S. Shubina, Maria Haver, Kenan E. Matthews, Benjamin D. Buck, Sarah Kacmarek, Robert M. Noviski, Natan N. TI Wheeze Detection in the Pediatric Intensive Care Unit: Comparison Among Physician, Nurses, Respiratory Therapists, and a Computerized Respiratory Sound Monitor SO RESPIRATORY CARE LA English DT Article DE wheeze; computerized respiratory sound monitor; PulmoTrack; pediatric intensive care unit; inter-rater agreement; auscultation ID AIR-FLOW OBSTRUCTION; LUNG SOUNDS; METHACHOLINE CHALLENGE; CHILDREN; ASTHMA; SYSTEM; NOISE; SIGNS AB OBJECTIVE: To correlate wheeze detection in the pediatric intensive care unit among staff members (a physician, nurses, and respiratory therapists [RTs]) and digital recordings from a computerized respiratory sound monitor (PulmoTrack). METHODS: We prospectively studied 11 patients in the pediatric intensive care unit. A physician, nurses, and RTs auscultated the patients and recorded their opinions about the presence of wheeze at baseline and then every hour for 6 hours. The clinician auscultated while the PulmoTrack recorded the lung sounds. The data were analyzed by a technician trained in interpretation of acoustic data and by a panel of experts blinded to the source of the recorded data, who scored all tracks for the presence or absence of wheeze. The degree of correlation among the expert panel, the staff, and the PulmoTrack was evaluated with the Kappa coefficient and McNemar's test. The determinations of the expert panel were taken as the true state (accepted standard). RESULTS: The PulmoTrack and expert panel were in agreement on detection of wheeze during inspiration, expiration, and the whole breath cycle; in all cases the Kappa coefficients were 0.54, 0.42, and 0.50 respectively. The PulmoTrack was significantly more sensitive than the physician (P = .002), nurses (P < .001), or RTs (P = .001). However, the specificity of the PulmoTrack was not significantly different from that of the physician, nurses, or RTs. CONCLUSIONS: Between the physician, RTs, and nurses there was agreement about the presence of wheeze in critically ill patients in the pediatric intensive care unit. Compared to the objective acoustic measurements from the PulmoTrack, the intensive care unit staff was similar in their ability to detect the absence of wheeze. The PulmoTrack was better than the staff in detecting wheeze. C1 [Matthews, Benjamin D.; Buck, Sarah] Harvard Univ, Div Pediat Crit Care Med, MassGen Hosp Children, Sch Med, Cambridge, MA 02138 USA. [Haver, Kenan E.] Harvard Univ, Div Pediat Pulm, MassGen Hosp Children, Sch Med, Cambridge, MA 02138 USA. [Kacmarek, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Resp Care, Boston, MA USA. RP Prodhan, P (reprint author), Univ Arkansas Med Sci, Div Pediat Crit Care Med, Arkansas Childrens Hosp, Little Rock, AR 72205 USA. FU Karmel Medical Acoustic Technologies, Yokneam Illit, Israel FX This research was supported by Karmel Medical Acoustic Technologies, Yokneam Illit. Israel. The authors report no conflicts of interest related to the content of this paper. NR 31 TC 12 Z9 12 U1 0 U2 3 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD OCT PY 2008 VL 53 IS 10 BP 1304 EP 1309 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 359LT UT WOS:000259988900008 PM 18811991 ER PT J AU Carvounis, PE Kopel, AC Kuhl, DP Heffez, J Pepple, K Holz, ER AF Carvounis, Petros E. Kopel, Andrew C. Kuhl, Derek P. Heffez, Jordan Pepple, Kathryn Holz, Eric R. TI 25-GAUGE VITRECTOMY USING SULFUR HEXAFLUORIDE AND NO PRONE POSITIONING FOR REPAIR OF MACULAR HOLES SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE macular hole; 25-gauge vitrectomy ID AUTOLOGOUS PLATELET CONCENTRATE; LIMITING MEMBRANE REMOVAL; PARS-PLANA VITRECTOMY; INTRAOCULAR TAMPONADE; SURGICAL-MANAGEMENT; VITREOUS SURGERY; RANDOMIZED-TRIAL; DURATION; FACE; PATHOGENESIS AB Purpose: To report on the outcomes of 25-gauge pars plana vitrectomy using sulfur hexafluoride and no prone positioning for repair of macular holes. Methods: Retrospective case series of 44 consecutive patients who underwent pars plana vitrectomy with internal limiting membrane peeling for repair of stages 2 to 4 idiopathic macular holes using 20% to 30% sulfur hexafluoride. No postoperative prone positioning or gas augmentation was used. Results: The macular hole closure rate was 88.6%. There were no differences in the macular hole closure rates between phakic and pseudophakic patients (21 of 23 vs. 17 of 21, respectively) or among stages 2, 3, and 4 macular holes (12 of 13, 20 of 23, and 7 of 8, respectively). In eyes successfully operated on, visual acuity improved from 0.61 logarithm of the minimal angle of resolution (logMAR) (20 of 82) preoperatively to 0.483 logMAR (20 of 61) at 1 month and 0.396 logMAR (20 of 50) at a mean final follow-up of 10.8 months. Adverse effects were elevation of intraocular pressure to >30 mmHg in 7 (13.6%) of 44 patients on the first postoperative day, postoperative retinal detachments in 2 (4.5%) of 44 patients, and progression of cataract requiring cataract surgery in 7 (30.4%) of 23 phakic patients during follow-up. Conclusions: Macular hole closure rates similar to those achieved using pars plana vitrectomy with perfluoropropane and prone positioning can be achieved using sutureless 25-gauge vitrectomy with sulfur hexafluoride tamponade and no prone positioning for both phakic and pseudophakic patients. RETINA 28:1188-1192, 2008 C1 [Holz, Eric R.] Baylor Coll Med, Cullen Eye Inst, Dept Ophthalmol, Houston, TX 77030 USA. [Carvounis, Petros E.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Kuhl, Derek P.] Retina Ctr, Bryan, TX USA. RP Holz, ER (reprint author), Baylor Coll Med, Cullen Eye Inst, Dept Ophthalmol, 6565 Fannin,NC 205, Houston, TX 77030 USA. EM eholz@bcm.tmc.edu RI Pepple, Kathryn /J-6229-2016; OI Carvounis, Petros/0000-0002-3879-3486 NR 33 TC 20 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2008 VL 28 IS 9 BP 1188 EP 1192 DI 10.1097/IAE.0b013e318177f9a8 PG 5 WC Ophthalmology SC Ophthalmology GA 366IM UT WOS:000260474200002 PM 19430387 ER PT J AU Kiss, S Vavvas, D AF Kiss, Szilard Vavvas, Demetrios TI 25-Gauge Transconjunctival Sutureless Pars Plana Vitrectomy for the Removal of Retained Lens Fragments and Intraocular Foreign Bodies SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID VITREORETINAL DISEASES; CATARACT-SURGERY; SILICONE OIL; 20-GAUGE; SYSTEM; OUTCOMES; INSTRUMENTS; MANAGEMENT C1 [Kiss, Szilard; Vavvas, Demetrios] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Vavvas, D (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM demetrios_vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 NR 27 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2008 VL 28 IS 9 BP 1346 EP 1351 DI 10.1097/IAE.0b013e318180ab7a PG 6 WC Ophthalmology SC Ophthalmology GA 366IM UT WOS:000260474200027 PM 18685539 ER PT J AU Yu, ZF Catzlano, PJ AF Yu, Zi-Fan Catzlano, Paul J. TI A simulation study of quantitative risk assessment for bivariate continuous outcomes SO RISK ANALYSIS LA English DT Article DE benchmark dose; dose response modeling; Monte Carlo; multiple outcomes; percentile regression ID DEVELOPMENTAL TOXICOLOGY AB The neurotoxic effects of chemical agents are often investigated in controlled studies on rodents, with binary and continuous multiple endpoints routinely collected. One goal is to conduct quantitative risk assessment to determine safe dose levels. Yu and Catalano (2005) describe a method for quantitative risk assessment for bivariate continuous outcomes by extending a univariate method of percentile regression. The model is likelihood based and allows for separate dose-response models for each outcome while accounting for the bivariate correlation. The approach to benchmark dose (BMD) estimation is analogous to that for quantal data without having to specify arbitrary cutoff values. In this article, we evaluate the behavior of the BMD relative to background rates, sample size, level of bivariate correlation, dose-response trend, and distributional assumptions. Using simulations, we explore the effects of these factors on the resulting BMD and BMDL distributions. In addition, we illustrate our method with data from a neurotoxicity study of parathion exposure in rats. C1 [Yu, Zi-Fan] Stat Collaborat Inc, Washington, DC 20036 USA. [Catzlano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Catzlano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Yu, ZF (reprint author), Stat Collaborat Inc, 1650 Massachusetts Ave, Washington, DC 20036 USA. EM fan-fan@statcollab.com FU National Institute of Environmental Health Sciences [ES06900, T32 ES07142-18]; National Cancer Institute [CA48061] FX This work was supported by Grants ES06900 and T32 ES07142-18 from the National Institute of Environmental Health Sciences and Grant CA48061 from the National Cancer Institute. The authors thank Drs. Lorenz Rhomberg, Louise Ryan, and Meredith Regan for helpful comments, and Dr. Virginia Moser at the U. S. EPA for the use of the example data. NR 10 TC 1 Z9 1 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD OCT PY 2008 VL 28 IS 5 BP 1415 EP 1430 DI 10.1111/j.1539-6924.2008.01082.x PG 16 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 350OT UT WOS:000259363300018 PM 18631306 ER PT J AU Daumit, GL Goff, DC Meyer, JM Davis, VG Nasrallah, HA McEvoy, JP Rosenheck, R Davis, SM Hsiao, JK Stroup, TS Lieberman, JA AF Daumit, Gail L. Goff, Donald C. Meyer, Jonathan M. Davis, Vicki G. Nasrallah, Henry A. McEvoy, Joseph P. Rosenheck, Robert Davis, Sonia M. Hsiao, John K. Stroup, T. Scott Lieberman, Jeffrey A. TI Antipsychotic effects on estimated 10-year coronary heart disease risk in the CATIE schizophrenia study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Antipsychotic; Coronary heart disease risk; Blood pressure; Cholesterol ID METABOLIC SYNDROME; MENTAL-ILLNESS; CARDIOVASCULAR RISK; WEIGHT-GAIN; MORTALITY; SMOKING; GLUCOSE; LIPIDS; TRIAL; HALOPERIDOL AB Objective: Persons with schizophrenia die earlier than the general population, in large part due to cardiovascular disease. The study objective was to examine effects of different antipsychotic treatments on estimates of 10-year coronary heart disease (CHD) risk calculated by the Framingham Heart Study formula. Method: Change in 10-year risk for CHD was compared between treatment groups in 1125 patients followed for 18 months or until treatment discontinuation in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial. Results: The covariate-adjusted mean change in 10-year CHD risk differed significantly between treatments. Olanzapine was associated with a 0.5% (SE 0.3) increase and quetiapine, a 0.3% (SE 0.3) increase; whereas risk decreased in patients treated with perphenazine, -0.5% (SE 0.3), risperidone, -0.6% (SE 0.3), and ziprasidone -0.6% (SE 0.4). The difference in 10-year CHD risk between olanzapine and risperidone was statistically significant (p=0.004). Differences in estimated 10-year CHD risk between drugs were most marked in the tertile of subjects with a baseline CHD risk of at least 10%. Among individual CHD risk factors used in the Framingham formula, only total and HDL cholesterol levels differed between treatments. Conclusions: These results indicate that the impact on 10-year CHD risk differs significantly between antipsychotic agents, with olanzapine producing the largest elevation in CHD risk of the agents studied in CATIE. (c) 2008 Elsevier B.V. All rights reserved. C1 [Daumit, Gail L.] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21287 USA. [Goff, Donald C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Freedom Trail Clin,Lindemann Mental, Boston, MA 02114 USA. [Meyer, Jonathan M.] Univ Calif San Diego, Vet Adm Med Ctr, San Diego, CA 92161 USA. [Davis, Vicki G.] Univ N Carolina, Collaborat Studies Coordinating Ctr, Dept Biostat, Coordinating Ctr 400,Bank Amer Ctr, Chapel Hill, NC 27514 USA. [Nasrallah, Henry A.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45267 USA. [McEvoy, Joseph P.] Duke Univ, Dept Psychiat, John Umstead Hosp, Butner, NC 27509 USA. [Rosenheck, Robert] Yale Univ, Dept Psychiat, West Haven, CT 06516 USA. [Davis, Sonia M.] Quintiles Inc, Morrisville, NC 27560 USA. [Hsiao, John K.] NIMH, Adult Treatment & Prevent Intervent Res Branch, Rockville, MD 20852 USA. [Stroup, T. Scott] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Lieberman, Jeffrey A.] Columbia Univ, Dept Psychiat, NYS Psychiat Inst, New York, NY 10032 USA. RP Daumit, GL (reprint author), Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Suite 2-500, Baltimore, MD 21287 USA. EM gdaumit@jhmi.edu; goff@psych.mgh.harvard.edu; jmmeyer@ucsd.edu; Vicki.davis@mail.cscc.unc.edu; Henry.nasrallah@uc.edu; jpmcevoy@duke.edu; Robert.rosenheck@yale.edu; Sonia.davis@quintiles.com; jh23f@nih.gov; Scott_stroup@med.unc.edu; jlieberman@pi.cpmc.columbia.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU National Institute of Mental Health [1MH900001] FX The CATIE Schizophrenia Trial was supported by National Institute of Mental Health, Grant No. 1MH900001. The NIMH and study principal investigators are responsible for the design and conduct of the trial, and the primary analyses. There is no industry involvement in these activities. NR 38 TC 116 Z9 118 U1 7 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2008 VL 105 IS 1-3 BP 175 EP 187 DI 10.1016/j.schres.2008.07.006 PG 13 WC Psychiatry SC Psychiatry GA 367ZU UT WOS:000260591900019 PM 18775645 ER PT J AU Kelley, ME Haas, GL van Kammen, DP AF Kelley, Mary E. Haas, Gretchen L. van Kammen, Daniel P. TI Longitudinal progression of negative symptoms in schizophrenia: A new look at an old problem SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Negative symptoms; Longitudinal data; Ordinal data; Symptomatology ID NEUROLEPTIC TREATMENT; CONSENSUS STATEMENT; DEFICIT; REPLICATION; HALOPERIDOL; DISTINCTION; DEFINITION; VALIDATION; REGRESSION; DICHOTOMY AB Objective: Longitudinal analysis is crucial in determining the ability of new interventions to successfully reduce negative symptoms in schizophrenia. However, there are still conflicting reports as to whether there are significant treatment effects on these symptoms and the extent of these effects. We examine the possible effects of analysis method on these questions. Methods: We use generalized linear mixed models (GLMM) to assess the change in specific negative symptom items following treatment changes in two separate cohorts of schizophrenia patients, one chronic and one first episode. Results: Both data sets indicate that examining the change in prevalence of moderate to severe symptoms provides a useful estimate of the effect size associated with changes in treatment that often differs from that given using analysis of means. Conclusions: The use of categorical longitudinal methods may be critical to determining the responsiveness of negative symptoms to treatment as well as determining the stability of these symptoms over time. (c) 2008 Elsevier B.V. All rights reserved. C1 [Kelley, Mary E.] Emory Univ, Dept Biostat, RSPH, Atlanta, GA 30322 USA. [Haas, Gretchen L.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. [Haas, Gretchen L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [van Kammen, Daniel P.] CHDI Inc, New York, NY USA. RP Kelley, ME (reprint author), Emory Univ, Dept Biostat, RSPH, Rm 352,1518 Clifton Rd NE, Atlanta, GA 30322 USA. EM mekelle@emory.edu FU NIMH [R01MH44-841, P50MH45156-14]; NIH/NCRR/GCRC [M01 RR00056]; VISN 4 Mental Illness Research and Clinical Center (MIRECC); VA Merit Review Board FX This publication was supported, in part, by funds received from NIMH R01MH44-841 (PI - DvK), P50MH45156-14 (P.I. - David A. Lewis), the NIH/NCRR/GCRC grant #M01 RR00056, and pilot funding from the VISN 4 Mental Illness Research and Clinical Center (MIRECC), as well as the VA Merit Review Board (PI - DvK). The funding sources had no further role in study design or implementation, or the writing and decision to submit the manuscript. NR 55 TC 8 Z9 8 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2008 VL 105 IS 1-3 BP 188 EP 196 DI 10.1016/j.schres.2008.06.003 PG 9 WC Psychiatry SC Psychiatry GA 367ZU UT WOS:000260591900020 PM 18619815 ER PT J AU Batki, SL Leontieva, L Dimmock, JA Ploutz-Snyder, R AF Batki, Steven L. Leontieva, Luba Dimmock, Jacqueline A. Ploutz-Snyder, Robert TI Negative symptoms are associated with less alcohol use, craving, and "high" in alcohol dependent patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Alcohol; PANSS; Negative symptom; Positive symptom; Naltrexone; Craving ID COMORBID SUBSTANCE-USE; DUAL DIAGNOSIS; SCALE; ABUSE; DISORDERS AB Background: Alcohol use disorders (AUDs) frequently co-occur with and exacerbate schizophrenia, yet the specific relationships between schizophrenia symptoms and alcohol use remain unclear. Methods: PANSS scores were correlated with measures of alcohol and other substance use in patients with schizophrenia-spectrum disorders and AUDs entering a trial of monitored naltrexone treatment. Data were analyzed from the first 80 participants; 55% had schizophrenia and 45% had schizoaffective disorder. All had AUDs; 95% had alcohol dependence and 5% alcohol abuse; 34% also had cannabis abuse/dependence and 31% cocaine abuse/dependence. Results: PANSS Negative scores were inversely correlated with Addiction Severity Index alcohol composite scores, alcohol craving, quality of alcohol "high" (euphoria), and with frequency of cannabis use. An exploratory analysis indicated that the negative symptoms that may most strongly con-elate with less alcohol use, craving and/or euphoria were passive/apathetic social withdrawal, blunted affect, difficulty in abstract thinking, and stereotyped thinking. Higher PANSS Composite scores, indicating the predominance of positive over negative PANSS symptoms, correlated with more alcohol craving and cannabis use. Higher PANSS General scores were associated with more alcohol craving. Conclusions: These findings extend previous reports of the association of negative schizophrenia symptoms with less alcohol and substance use to patients with AUDs and indicate that this relationship also includes less alcohol craving and less alcohol euphoria. The findings may also provide some initial evidence that specific negative symptoms may be keys to these relationships. (c) Published by Elsevier B.V. C1 [Batki, Steven L.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA 94143 USA. [Batki, Steven L.; Leontieva, Luba; Dimmock, Jacqueline A.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Ploutz-Snyder, Robert] SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. RP Batki, SL (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr 1169, Dept Psychiat, 4150 Clement St, San Francisco, CA 94121 USA. EM steven.batki@ucsf.edu; dimmockj@upstate.edu FU NIAAA [5RO1 AA013655] FX NIAAA grant 5RO1 AA013655. The NIAAA had no further role in the study design; in the collection, analysis, and interpretation of the data; in the writing of report; and in the decision to submit the paper for publication. NR 22 TC 7 Z9 8 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2008 VL 105 IS 1-3 BP 201 EP 207 DI 10.1016/j.schres.2008.06.020 PG 7 WC Psychiatry SC Psychiatry GA 367ZU UT WOS:000260591900022 PM 18701256 ER PT J AU Gazit, R Weissman, IL Rossi, DJ AF Gazit, Roi Weissman, Irving L. Rossi, Derrick J. TI Hematopoietic stem cells and the aging hematopoietic system SO SEMINARS IN HEMATOLOGY LA English DT Article ID AGE-RELATED-CHANGES; SELF-RENEWAL; REPOPULATING ABILITY; APLASTIC-ANEMIA; BONE-MARROW; PROLIFERATIVE CAPACITY; DYSKERATOSIS-CONGENITA; OXIDATIVE STRESS; PROGENITOR CELLS; B-LYMPHOPOIESIS AB The etiology of the age-associated pathophysiological changes of the hematopoietic system including the onset of anemia, diminished adaptive immune competence, and myelogenous disease development are underwritten by the loss of normal homeostatic control. As tissue and organ homeostasis in adults is primarily mediated by the activity of stem and progenitor cells, it has been suggested that the imbalances accompanying aging of the hematopoietic system may stem from alterations in the prevalence and/or functional capacity of hematopoietic stem cells (HSCs) and progenitors. In this review, we examine evidence implicating a role for stem cells in the aging of the hematopoietic system, and focus on the mechanisms suggested to contribute to stem cell aging. C1 [Gazit, Roi; Rossi, Derrick J.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Immune Dis Inst, Boston, MA USA. [Gazit, Roi; Rossi, Derrick J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Weissman, Irving L.] Stanford Univ, Ctr Canc, Stanford Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Weissman, Irving L.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. RP Rossi, DJ (reprint author), 200 Longwood Ave, Boston, MA 02115 USA. EM rossi@idi.harvard.edu OI Gazit, Roi/0000-0002-0548-2147 FU YAD-HANADIV; National Institutes of Aging [AG029760-02] FX R.G. was supported by a fellowship from YAD-HANADIV, and D.J.R. was supported by a grant from the National Institutes of Aging, AG029760-02. NR 72 TC 37 Z9 51 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2008 VL 45 IS 4 BP 218 EP 224 DI 10.1053/j.seminhematol.2008.07.010 PG 7 WC Hematology SC Hematology GA 353QT UT WOS:000259584000003 PM 18809091 ER PT J AU Yin, YP Chen, XS Wang, HC Shi, MQ Wei, WH Zhu, BY Yu, YH Tucker, JD Cohen, MS AF Yin, Y-P Chen, X-S Wang, H-C Shi, M-Q Wei, W-H Zhu, B-Y Yu, Y-H Tucker, J. D. Cohen, M. S. TI Detection of acute HIV infections among sexually transmitted disease clinic patients: a practice in Guangxi Zhuang Autonomous Region, China SO SEXUALLY TRANSMITTED INFECTIONS LA English DT Article ID TESTING POPULATION; PREVENTION; MEN AB Detection of people with acute HIV infection (AHI) affords an important opportunity for early HIV treatment and prevention. HIV RNA reverse transcriptase-polymerase chain reaction (RT-PCR) testing with two-stage pooling scheme was used to detect the AHI in specimens collected from sexually transmitted disease (STD) clinic patients in Guangxi, China. A total of 246 HIV RNA tests were required to screen 11 395 samples negative for conventional enzyme immunoassay (EIA) and Western blot assays, and five AHI cases (0.04%, 95% CI 0.02% to 0.10%) with a high viral load (median of 265 677 copies per ml) were detected. The total expenditure for RT-PCR testing reflected an added cost of $2.9 per specimen screened and $6575 per additional case of AHI identified among the study population. This study supports the feasibility of pooled RNA testing in addition to detection of HIV infections among patients at STD clinics in China, but the cost effectiveness should be carefully considered. C1 [Yin, Y-P; Chen, X-S; Wang, H-C; Shi, M-Q; Wei, W-H; Yu, Y-H] Chinese Acad Med Sci, Natl Ctr STD Control, Nanjing 210042, Peoples R China. [Yin, Y-P; Chen, X-S; Wang, H-C; Shi, M-Q; Wei, W-H; Yu, Y-H] Peking Union Med Coll, Inst Dermatol, Nanjing 210042, Peoples R China. [Zhu, B-Y] Guangxi Autonomous Reg Inst Dermatol, Nanning, Peoples R China. [Tucker, J. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cohen, M. S.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. RP Chen, XS (reprint author), Chinese Acad Med Sci, Natl Ctr STD Control, 12 Jiangwangmiao St, Nanjing 210042, Peoples R China. EM chenxs@vip.163.com FU Family Health International (FHI); UNC-CH Fogarty Center; China CDC National Center for STD Control FX This study was financially supported by the Family Health International (FHI), the UNC-CH Fogarty Center and China CDC National Center for STD Control. We thank the staff of the collaborating STD clinics in Nanning, Yulin, Guigang, Liuzhou, Liujiang, Qinzhou and Baihai where this study took place and the participants of this study for their wonderful cooperation. We appreciate Drs Jeanine Bardon and Graham Neilsen from the Family Health International Asia Pacific Department in Bangkok for their suggestions at several stages of this study, Dr Susan Fiscus at UNC at Chapel Hill and her team for laboratory guidance and Dr Fujie Xu for her technical support during her visit to sites. Additional staff essential to the project include Drs Xing Gao, Qiang Chen and Mu-Sang Liu, Mrs Ming-Ying Zhong and Ms Xue-Qin Dai from National Center for STD Control in Nanjing. Special thanks to the Jiangsu Province's Key Medical Center of Dermatology and Venearology in Nanjing China. NR 10 TC 1 Z9 1 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1368-4973 J9 SEX TRANSM INFECT JI Sex. Transm. Infect. PD OCT PY 2008 VL 84 IS 5 BP 350 EP 351 DI 10.1136/sti.2007.028837 PG 2 WC Infectious Diseases SC Infectious Diseases GA 351CJ UT WOS:000259401800006 PM 18305121 ER PT J AU Kamath, R Strichartz, G Rosenthal, D AF Kamath, Ravi Strichartz, Gary Rosenthal, Daniel TI Cartilage toxicity from local anesthetics SO SKELETAL RADIOLOGY LA English DT Article ID BOVINE ARTICULAR CHONDROCYTES; IN-VITRO; INTRAARTICULAR BUPIVACAINE; GLENOHUMERAL CHONDROLYSIS; ROPIVACAINE; ARTHROSCOPY; SHOULDER; JOINT; CELLS C1 [Kamath, Ravi; Rosenthal, Daniel] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Strichartz, Gary] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. RP Kamath, R (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM rkamath@partners.org NR 25 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD OCT PY 2008 VL 37 IS 10 BP 871 EP 873 DI 10.1007/s00256-008-0567-8 PG 3 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 342BY UT WOS:000258760800001 PM 18685843 ER PT J AU Patti, JW Ouellette, H Bredella, MA Torriani, M AF Patti, Jay W. Ouellette, Hugue Bredella, Miriam A. Torriani, Martin TI Impingement of lesser trochanter on ischium as a potential cause for hip pain SO SKELETAL RADIOLOGY LA English DT Article DE ischium; lesser trochanter; impingement; hip AB The bony anatomy of the hip leads to a limited array of impingement syndromes, more frequently resulting from abnormal contact between the femoral neck and acetabulum. We report an unusual case of osseous impingement between the lesser trochanter and ischium, with involvement of the intervening quadratus femoris muscle. While the prevalence and etiology of this finding is unclear, it may represent a cause for hip pain. C1 [Patti, Jay W.; Ouellette, Hugue; Bredella, Miriam A.; Torriani, Martin] Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. [Patti, Jay W.; Ouellette, Hugue; Bredella, Miriam A.; Torriani, Martin] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Radiol, 55 Fruit St,YAW 6048, Boston, MA 02114 USA. EM mtorriani@hms.harvard.edu NR 2 TC 45 Z9 49 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD OCT PY 2008 VL 37 IS 10 BP 939 EP 941 DI 10.1007/s00256-008-0551-3 PG 3 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 342BY UT WOS:000258760800011 PM 18682931 ER PT J AU Christie, MA Bolortuya, Y Chen, LC McKenna, JT McCarley, RW Strecker, RE AF Christie, Michael A. Bolortuya, Yunren Chen, Li Chao McKenna, James T. McCarley, Robert W. Strecker, Robert E. TI Microdialysis elevation of adenosine in the basal forebrain produces vigilance impairments in the rat Psychomotor Vigilance Task SO SLEEP LA English DT Article DE adenosine; basal forebrain; microdialysis; attention; vigilance; rat; sleep; sleep deprivation; sleepiness; PVT; caffeine ID SUSTAINED ATTENTION PERFORMANCE; TOTAL SLEEP-DEPRIVATION; BEHAVIORAL STATE; COGNITIVE FUNCTIONS; DOSE-RESPONSE; MODULATION; WAKEFULNESS; RESTRICTION; OPERATIONS; MODAFINIL AB Study Objective: The inhibitory neuromodulator adenosine has been proposed as a homeostatic sleep factor that acts potently in the basal forebrain (BF) to increase sleepiness, Here 300 mu M of adenosine was dialyzed in the BF of rats, and the effect on vigilance was determined in the rat Psychornotor Vigilance Task (rPVT). Design: Rats experienced all experimental conditions in a repeated-measures, cross-over design. Patients or Participants: Twelve young adult male Fischer-Norway rats. Interventions: Sustained attention performance in the rPVT was evaluated following 2 hours of bilateral microdialysis perfusion of vehicle, adenosine (300 mu M), or codialysis of 300 mu M of adenosine with the A, receptor antagonist 8-cyclopentyltheophylline. Measurements and Results: During rPVT performance, response latencies and performance lapses increased significantly after adenosine dialysis when compared with baseline (no dialysis) or vehicle dialysis sessions. The codialysis of 8-cyclopentyltheophylline with adenosine completely blocked the effects produced by adenosine alone, resulting in performance equivalent to that of the vehicle sessions. Conclusions: Pharmacologic elevation of BF adenosine in rats produced vigilance impairments resembling the effect of sleep deprivation on vigilance performance in both man and rats. This effect of exogenous adenosine was completely blocked by codialysis with an adenosine A, receptor antagonist. The results are consistent with the hypothesis that sleep loss induces elevations of BF adenosine that, acting via A, receptors, lead to increased sleepiness and impaired vigilance. C1 VA Boston Healthcare Syst, Brockton, MA USA. Harvard Univ, Sch Med, Brockton, MA 02401 USA. RP Strecker, RE (reprint author), Res 151-C,940 Belmont St, Brockton, MA 02301 USA. EM michael_christie@hms.harvard.edu; robert_strecker@hms.har-vard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NHLBI NIH HHS [T32 HL07901, P50 HL060292, T32 HL007901]; NIMH NIH HHS [F32 MH070156, R37 MH039683] NR 40 TC 25 Z9 25 U1 1 U2 2 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 OCT 1 PY 2008 VL 31 IS 10 BP 1393 EP 1398 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 354PG UT WOS:000259650900008 PM 18853936 ER PT J AU Mei, Y Cannizzaro, C Park, HS Xu, QB Bogatyrev, SR Yi, K Goldman, N Langer, R Anderson, DG AF Mei, Ying Cannizzaro, Christopher Park, Hyoungshin Xu, Qiaobing Bogatyrev, Said R. Yi, Kevin Goldman, Nathan Langer, Robert Anderson, Daniel G. TI Cell-Compatible, Multicomponent Protein Arrays with Subcellular Feature Resolution SO SMALL LA English DT Article DE microscale direct writing; protein microarrays; cell adhesion; subcellular resolution ID DIP-PEN NANOLITHOGRAPHY; SOFT LITHOGRAPHY; ADHESION; MICROARRAYS; GENERATION; MIGRATION; SURFACES; MOTILITY; TENSION; SHAPE C1 [Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA. [Mei, Ying; Xu, Qiaobing; Bogatyrev, Said R.; Yi, Kevin; Goldman, Nathan; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Park, Hyoungshin] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Anderson, DG (reprint author), MIT, David H Koch Inst Integrat Canc Res, 45 Carleton St,Bldg E25-342, Cambridge, MA 02142 USA. EM dgander@mit.edu FU Mitsubishi Chemical Company; NIH [R01 DE016516-03] FX We gratefully acknowledge Jim Johnson and Gabor Bethlendy from Bioforce Nanoscience for expert help and advice on NanoeNabler instrument. We also thank Ed Luther for the help with the laser scanning cytometry. Funding was kindly provided by the Mitsubishi Chemical Company and NIH grant R01 DE016516-03. NR 33 TC 24 Z9 24 U1 1 U2 12 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-6810 J9 SMALL JI Small PD OCT PY 2008 VL 4 IS 10 BP 1600 EP 1604 DI 10.1002/smll.200800363 PG 5 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 362ML UT WOS:000260201700003 PM 18844310 ER PT J AU Kim, JH Studer, RK Sowa, GA Vo, NV Kang, JD AF Kim, Joo Han Studer, Rebecca K. Sowa, Gwendolyn A. Vo, Nam Viet Kang, James D. TI Activated macrophage-like THP-1 cells modulate anulus fibrosus cell production of inflammatory mediators in response to cytokines SO SPINE LA English DT Article DE low back pain; intervertebral disc; anulus fiborsus; macrophages; coculture; cytokines ID NECROSIS-FACTOR-ALPHA; INTERVERTEBRAL-DISC DEGENERATION; LOW-BACK-PAIN; NITRIC-OXIDE; HERNIATED DISC; MATRIX METALLOPROTEINASES; INTERLEUKIN-6; EXPRESSION; PATHOGENESIS; INDUCTION AB Study Design. Anulus fibrosus (AF) cells obtained from patients undergoing surgery were cocultured with macrophage-like cells and production of inflammatory mediators was analyzed by quantitative assay. Objective. To investigate the role of macrophages in AF cell production of inflammatory mediators by cytokines stimulation. Summary of Background Data. Discogenic pain caused by anular disruption is an important cause of low back pain and recent studies show the presence of macrophages in symptomatic discs but not in normal and aging discs. We hypothesize that macrophages play a major role in development of symptomatic disc. Methods. Human AF cells were cocultured with phorbol myristate acetate stimulated macrophage-like THP-1 cells. The conditioned medium from cells cultured alone or in coculture was assayed for cytokines by Enzyme-linked immunosorbent assay and nitric oxide (NO) by the Greiss method. Using the same outcome measures, comparisons of cell response to cytokines were made among macrophage-like cells, naive AF cells, and macrophage exposed AF cells. Results. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-6, and NO (TNF-alpha: 1.45 +/- 0.29 ng/mL, IL-8: 97.02 +/- 7.94 ng/mL, IL-6: 33.40 +/- 3.55 ng/mL, NO: 8.42 +/- 0.78 mu mol/L) were secreted in much greater amounts by cells maintained in coculture compared to macrophages (TNF-alpha: 0.78 +/- 0.12 ng/mL, IL-8: 58.04 +/- 4.44 ng/mL, IL-6: 0.14 +/- 0.03 ng/mL, NO: 0.30 +/- 0.08 mu mol/L) or AF cells cultured alone. In addition, IL-6 secretion from AF cells in response to TNF-alpha was up-regulated by coculture, however, IL-6 secretion in response to IL-1 beta was down-regulated in a dose-dependent manner. Coculture with macrophages also up-regulated AF cell secretion of IL-8 dose-dependently and downregulated NO to TNF-alpha or IL-1 beta stimulation. Conclusion. We conclude that exposure to macrophages, as can be expected after anular injury, can result in enhanced response to local inflammation. Although changes were observed in all inflammatory mediators after macrophage exposure, the most significant change was observed in IL-6 and IL-8, implicating these mediators in development of symptomatic disc. C1 [Kim, Joo Han; Sowa, Gwendolyn A.; Vo, Nam Viet; Kang, James D.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Ferguson Lab Orthopaed Res, Pittsburgh, PA 15261 USA. [Kim, Joo Han] Korea Univ, Coll Med, Dept Neurosurg, Seoul 136705, South Korea. [Studer, Rebecca K.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Sowa, Gwendolyn A.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA 15261 USA. RP Kang, JD (reprint author), Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Ferguson Lab Orthopaed Res, 200 Lothrop St,E1641 BST, Pittsburgh, PA 15261 USA. EM kangjd@upmc.edu RI Kim, Joo Han/B-8129-2014 OI Kim, Joo Han/0000-0002-4747-9763 FU Pittsburgh Foundation at Department of Orthopedic Surgery, University of Pittsburgh FX Foundation funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.; Supported by the Pittsburgh Foundation at Department of Orthopedic Surgery, University of Pittsburgh. NR 42 TC 23 Z9 26 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD OCT 1 PY 2008 VL 33 IS 21 BP 2253 EP 2259 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 354KF UT WOS:000259637800001 PM 18784630 ER PT J AU Aston, JAD Brown, EN Loh, WL Worsley, KJ Wu, YN AF Aston, John A. D. Brown, Emery N. Loh, Wei Liem Worsley, Keith J. Wu, Yingnian TI At the Interface of Statistics and Brain Science SO STATISTICA SINICA LA English DT Editorial Material C1 [Aston, John A. D.] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Aston, John A. D.] Acad Sinica, Taipei 115, Taiwan. [Brown, Emery N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Cambridge, MA 02139 USA. [Loh, Wei Liem] Natl Univ Singapore, Singapore 117548, Singapore. [Worsley, Keith J.] Univ Chicago, Chicago, IL 60637 USA. [Wu, Yingnian] Univ Calif Los Angeles, Los Angeles, CA USA. RP Aston, JAD (reprint author), Univ Warwick, Coventry CV4 7AL, W Midlands, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD OCT PY 2008 VL 18 IS 4 BP 1201 EP 1202 PG 2 WC Statistics & Probability SC Mathematics GA 374TR UT WOS:000261067100001 ER PT J AU Chou, SHY Smith, EE Badjatia, N Nogueira, RG Sims, JR Ogilvy, CS Rordorf, GA Ayata, C AF Chou, Sherry H. -Y. Smith, Eric E. Badjatia, Neeraj Nogueira, Raul G. Sims, John R., II Ogilvy, Christopher S. Rordorf, Guy A. Ayata, Cenk TI A randomized, double-blind, placebo-controlled pilot study of simvastatin in aneurysmal subarachnoid hemorrhage SO STROKE LA English DT Article DE vasospasm; delayed cerebral ischemia; clinical trial ID CEREBRAL VASOSPASM; STATIN USE; PRAVASTATIN; INCREASES; TRIAL AB Background and Purpose - Studies suggest statins ameliorate aneurysmal subarachnoid hemorrhage (SAH)-induced cerebral vasospasm and ischemic complications. We tested safety and feasibility of simvastatin 80 mg/d for vasospasm prevention in SAH patients. Methods - Thirty-nine statin-naive Fisher grade 3 SAH subjects were double-blind randomized to receive simvastatin 80 mg/d (n = 19) or placebo (n = 20), stratified by Hunt and Hess grade. Primary end points were death and drug morbidity. Results - Mortality was 3/20 in the placebo and 0/19 in the simvastatin group. Study drug was withdrawn in 1 subject in each treatment group for reversible liver enzyme or creatine phosphokinase elevation. Angiographically-confirmed vasospasm occurred in 8/20 placebo and 5/19 simvastatin-treated subjects. Vasospasm-related ischemic infarcts developed in 5/20 placebo and 2/19 simvastatin-treated subjects. Conclusion - Simvastatin for the prevention of delayed cerebral ischemia is safe and feasible after SAH. A larger study is needed to test its efficacy. C1 [Chou, Sherry H. -Y.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Cambridge, MA 02138 USA. [Smith, Eric E.; Nogueira, Raul G.; Sims, John R., II; Rordorf, Guy A.; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Nogueira, Raul G.; Sims, John R., II; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Ogilvy, Christopher S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA USA. [Badjatia, Neeraj] Columbia Univ, Coll Phys & Surg, Dept Neurol & Neurosurg, New York, NY USA. RP Ayata, C (reprint author), 149 13th St,Room 6408, Charlestown, MA 02129 USA. EM cayata@partners.org RI Chou, Sherry/G-5779-2015; Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 FU National Institutes of Health NCRR [K30-RR022292-07] FX This work was supported by National Institutes of Health NCRR K30-RR022292-07 (S. H. C.), and a philanthropic donation to the MGH Stroke Service, administered by Dr Rordorf. The study was designed, executed and analyzed without influence from the financial sponsors. NR 6 TC 61 Z9 68 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2008 VL 39 IS 10 BP 2891 EP 2893 DI 10.1161/STROKEAHA.107.505875 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 354OK UT WOS:000259648700034 PM 18658043 ER PT J AU Yenari, M Kitagawa, K Lyden, P Perez-Pinzon, M AF Yenari, Midori Kitagawa, Kazuo Lyden, Patrick Perez-Pinzon, Miguel TI Metabolic downregulation - A key to successful neuroprotection? SO STROKE LA English DT Review DE cerebral ischemia; ischemic tolerance; hypothermia ID TRANSIENT ISCHEMIC ATTACKS; ASPHYXIAL CARDIAC-ARREST; PRESERVES MITOCHONDRIAL-FUNCTION; POSTISCHEMIC MILD HYPOTHERMIA; GLOBAL CEREBRAL-ISCHEMIA; TRAUMATIC BRAIN-INJURY; CYTOCHROME-C RELEASE; MODERATE HYPOTHERMIA; THERAPEUTIC HYPOTHERMIA; EXPERIMENTAL STROKE AB Background and Purpose - The search for effective neuroprotectants remains frustrating, particularly with regard to specific pharmaceuticals. However, laboratory studies have consistently shown remarkable neuroprotection with 2 nonpharmacological strategies - therapeutic hypothermia and ischemic preconditioning. Recent studies have shown that the mechanism of protection underlying both of these treatments is correlated to downregulation of cellular and tissue metabolism. Thus, understanding the mechanisms underlying such robust protective effects could lead to appropriate translation at the clinical level. In fact, hypothermia is already being used at many centers to improve neurological outcome from cardiac arrest. Methods - A systematic review of both topics is presented in terms of underlying pathophysiological mechanisms and application at the clinical level. Results - Although the mechanisms of protection for both therapeutic strategies are multifold, both share features of downregulating metabolism. Both therapeutic strategies are robust neuroprotectants, but translating them to the clinical arena is challenging, though not impossible, and clinical studies have shown or suggest benefits of both treatments. Conclusions - The strategy of metabolic downregulation should be further explored to identify effective neuroprotectants that can be easily applied clinically. C1 [Yenari, Midori] Univ Calif San Francisco, Dept Neurol, Neurol VAMC 127, San Francisco, CA 94121 USA. [Yenari, Midori] San Francisco VA Med Ctr, San Francisco, CA USA. [Kitagawa, Kazuo] Osaka Univ, Grad Sch Med, Dept Neurol, Osaka, Japan. [Lyden, Patrick] San Diego Vet Adm, Med Ctr, Neurol & Res Serv, San Diego, CA USA. [Lyden, Patrick] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Perez-Pinzon, Miguel] Univ Miami, Dept Neurol, Coral Gables, FL 33124 USA. RP Yenari, M (reprint author), Univ Calif San Francisco, Dept Neurol, Neurol VAMC 127, 4150 Clement St, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu FU NINDS [R01 NS40516, P50 NS014543, P01 NS37520, P50 NS044148]; American Heart Association Established Investigator Award FX The work was funded, in part, by grants NINDS R01 NS40516 (to M. A. Y.), P50 NS014543 (to M. A. Y.), P01 NS37520 (to M. A. Y.), P50 NS044148 (to P. D. L.), and the American Heart Association Established Investigator Award (to M. A. Y.). NR 102 TC 67 Z9 71 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2008 VL 39 IS 10 BP 2910 EP 2917 DI 10.1161/STROKEAHA.108.514471 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 354OK UT WOS:000259648700038 PM 18658035 ER PT J AU Gee, DW Willingham, FF Lauwers, GY Brugge, WR Rattner, DW AF Gee, Denise W. Willingham, Field F. Lauwers, Gregory Y. Brugge, William R. Rattner, David W. TI Natural orifice transesophageal mediastinoscopy and thoracoscopy: a survival series in swine SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE NOTES; Endoscopy; Thoracoscopy; Mediastinoscopy; Pleural biopsy ID PORCINE MODEL; ABDOMINAL EXPLORATION; ORGAN RESECTION; CHOLECYSTECTOMY; PERITONEOSCOPY; FEASIBILITY; ANASTOMOSIS; ENDOSCOPY AB Introduction Transesophageal endoscopic mediastinoscopy (MX) and thoracoscopy (TX) could reduce pain, eliminate intercostal neuralgia, provide better access to the posterior mediastinal compartment and pulmonary hilum, and improve cosmesis. The purpose of this study was to demonstrate the feasibility of transesophageal natural orifice translumenal endoscopic surgery (NOTES) and to determine the complications that might be seen in surviving animals. Methods Using cap endoscopic mucosal resection and blunt dissection, a 15-20 cm submucosal tunnel was created in the esophagus and an endoscope passed through the tunnel into the mediastinum. One swine underwent MX; three swine underwent both MX and TX. The mediastinal compartment, hilar lymph nodes, pleura, lung, and esophagus were identified. Esophageal closure was obtained via submucosal tunnel flap-valve alone (two swine) or reinforcement with mucosal clips (two swine). The esophagus, mediastinum, and thorax were examined at necropsy. The esophagus was excised and sent for pathological examination. Results NOTES MX and TX provided excellent visualization of mediastinal and thoracic structures. Pleural biopsy was easily accomplished. All animals survived the procedure, ate well, and showed no ill effects. Swine were sacrificed at either 8 or 12 days postoperatively. At necropsy, mild atelectasis was noted in each animal. One animal (mucosal clip closure) developed a fluid collection in the submucosal tunnel. There was no evidence of mediastinitis or thoracic contamination in any animals. Conclusions Transesophageal endoscopic mediastinoscopy and thoracoscopy provide excellent visualization of mediastinal and intrathoracic structures. Pleural biopsy can be easily obtained under direct visualization. Structures that are difficult to visualize via traditional cervical mediastinoscopy and thoracoscopy are seen well with this approach. The submucosal tunnel creates a flap-valve that, alone, may be sufficient for preventing esophageal leak. These procedures can be performed safely in swine with short-term survival. Further study with a larger sample size and longer survival is warranted. C1 [Gee, Denise W.; Rattner, David W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Wang Ambulatory Care Ctr 460, Boston, MA 02114 USA. [Willingham, Field F.; Brugge, William R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gastroenterol,Dept Med, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM drattner@partners.org OI Willingham, Field/0000-0002-7071-3001 NR 21 TC 46 Z9 50 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD OCT PY 2008 VL 22 IS 10 BP 2117 EP 2122 DI 10.1007/s00464-008-0073-z PG 6 WC Surgery SC Surgery GA 363DV UT WOS:000260247500002 PM 18636291 ER PT J AU Ball, BA Conley, AJ MacLaughlin, DT Grundy, SA Sabeur, K Liu, IKM AF Ball, B. A. Conley, A. J. MacLaughlin, D. T. Grundy, S. A. Sabeur, K. Liu, I. K. M. TI Expression of anti-Mullerian hormone (AMH) in equine granulosa-cell tumors and in normal equine ovaries SO THERIOGENOLOGY LA English DT Article DE anti-Mullerian hormone; granulosa-cell tumor; ovarian follicle; ovary; equine ID INHIBITING SUBSTANCE; MARES; SECRETION; MARKER; PREGNANCY; MICE AB Anti-Mullerian hormone (AMH), also known as Mullerian inhibiting substance (MIS), is expressed by granulosa cells in females of many mammalian species, and circulating AMH concentrations have been used to monitor granulosa-cell tumors (GCT) in women. The objective was to characterize expression of AMH in equine GCT, and in normal equine ovaries. based upon immunohistochemistry (IHC), using a polyclonal primary antibody directed against human AMH. Equine GCT (n = 27) and normal equine ovaries (n = 10) were examined by IHC, In addition, sera front lour mares with GCT were characterized for AMH bioactivity, based upon suppression of Mullerian duct development in the fetal rat. Immunolabeling with alpha-AMH was localized to granulosa cells in equine GCT, as well as within antral follicles in normal ovaries. Expression of AMH first appeared in granulosa cells of small growing, follicles and was most intense in small antral follicles; large antral or atretic follicles had reduced immunolabeling. Omission of the primary antibody or incubation of the primary antibody with the corresponding blocking peptide eliminated immunolabeling of granulosa cells in GCT and in normal antral follicles, confirming the specificity of the immunolabel. Sera from mares with GCT had increased AMH bioactivity compared to control sera. In conclusion, AMH was strongly expressed by granulosa cells in equine GCT and in normal anti-at follicles. Therefore, anti-Mullerian hormone may be a useful biomarker for detection of GCT in the horse. (c) 2008 Elsevier Inc. All rights reserved. C1 [Ball, B. A.; Conley, A. J.; Grundy, S. A.; Sabeur, K.; Liu, I. K. M.] Univ Calif Davis, Sch Vet Med, Dept Populat Hlth & Reprod, Davis, CA 95616 USA. [MacLaughlin, D. T.] Harvard Univ, Sch Med, Pediat Surg Res Labs, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ball, BA (reprint author), Univ Calif Davis, Sch Vet Med, Dept Populat Hlth & Reprod, Davis, CA 95616 USA. EM baball@ucdavis.edu FU State of California Pari-mutuel Fund FX Supported by the John P. Hughes Endowment and the Center for Equine Health, with funds provided by the State of California Pari-mutuel Fund, and contributions by private donors. The authors thank Ms. Andrea Brum for assistance with immunohistochemistry, Dr. Anja Stoll and Dr. Alejandro Esteller Vico for providing some of the tissues used in this study, as well as Ms. Coralie Munro for assistance with endocrine assays. NR 39 TC 27 Z9 30 U1 2 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0093-691X EI 1879-3231 J9 THERIOGENOLOGY JI Theriogenology PD OCT 1 PY 2008 VL 70 IS 6 BP 968 EP 977 DI 10.1016/j.theriogenology.2008.05.059 PG 10 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA 349KL UT WOS:000259279600010 PM 18599114 ER PT J AU Dzik, WS Beckman, N Selleng, K Heddle, N Szczepiorkowski, Z Wendel, S Murphy, M AF Dzik, Walter Sunny Beckman, Neil Selleng, Kathleen Heddle, Nancy Szczepiorkowski, Zbigniew Wendel, Silvano Murphy, Michael CA BEST Collaborative TI Errors in patient specimen collection: application of statistical process control SO TRANSFUSION LA English DT Article ID SAMPLE COLLECTION; TRANSFUSION; PERFORMANCE AB BACKGROUND: Errors in the collection and labeling of blood samples for pretransfusion testing increase the risk of transfusion-associated patient morbidity and mortality. Statistical process control (SPC) is a recognized method to monitor the performance of a critical process. An easy-to-use SPC method was tested to determine its feasibility as a tool for monitoring quality in transfusion medicine. STUDY DESIGN AND METHODS: SPC control charts were adapted to a spreadsheet presentation. Data tabulating the frequency of mislabeled and miscollected blood samples from 10 hospitals in five countries from 2004 to 2006 were used to demonstrate the method. Control charts were produced to monitor process stability. RESULTS: The participating hospitals found the SPC spreadsheet very suitable to monitor the performance of the sample labeling and collection and applied SPC charts to suit their specific needs. One hospital monitored subcategories of sample error in detail. A large hospital monitored the number of wrong-blood-in-tube (WBIT) events. Four smaller-sized facilities, each following the same policy for sample collection, combined their data on WBIT samples into a single control chart. One hospital used the control chart to monitor the effect of an educational intervention. CONCLUSION: A simple SPC method is described that can monitor the process of sample collection and labeling in any hospital. SPC could be applied to other critical steps in the transfusion processes as a tool for biovigilance and could be used to develop regional or national performance standards for pretransfusion sample collection. A link is provided to download the spreadsheet for free. C1 [Dzik, Walter Sunny] Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Natl Blood Serv, Lab Serv, Birmingham, W Midlands, England. Ernst Moritz Arndt Univ Greifswald, Dept Transfus, Greifswald, Germany. McMaster Univ, Dept Med, Hamilton, ON, Canada. Dartmouth Hitchcock Med Ctr, Dept Pathol & Med, Lebanon, NH 03766 USA. Hosp Sirio Libanes, Blood Bank, Sao Paulo, Brazil. John Radcliffe Hosp, Dept Transfus, Oxford OX3 9DU, England. RP Dzik, WS (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224,55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 NR 17 TC 18 Z9 21 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2008 VL 48 IS 10 BP 2143 EP 2151 DI 10.1111/j.1537-2995.2008.01824.x PG 9 WC Hematology SC Hematology GA 358KG UT WOS:000259915100016 PM 18673352 ER PT J AU Mechanic, MB Weaver, TL Resick, PA AF Mechanic, Mindy B. Weaver, Terri L. Resick, Patricia A. TI Risk factors for physical injury among help-seeking battered women - An exploration of multiple abuse dimensions SO VIOLENCE AGAINST WOMEN LA English DT Article DE battered women; help seeking; injury ID INTIMATE PARTNER VIOLENCE; DOMESTIC VIOLENCE; HEALTH CONSEQUENCES; STRESS-DISORDER; BRAIN-INJURY; STALKING AB Physical injuries among battered women represent risks for both acute and long-term physical health functioning. The current study assessed the nature and extent of minor and severe injuries among a help-seeking sample of battered women. Hierarchical regression analyses were conducted to assess the unique roles of physical violence, sexual coercion, psychological abuse, and stalking to the prediction of minor and severe injuries in battered women. Not unexpectedly, length of relationship abuse and severity of physical aggression were the most robust predictors of minor and severe physical injuries. Consistent with other research findings, psychological abuse and stalking, as a block, contributed uniquely to the prediction of severe injuries. Results are discussed in terms of implications for future research and intervention with battered women. C1 [Mechanic, Mindy B.] Calif State Univ Fullerton, Fullerton, CA 92634 USA. [Weaver, Terri L.] St Louis Univ, St Louis, MO 63103 USA. [Resick, Patricia A.] VA Boston Hlth Care Syst, Womens Hlth Sci Div, Natl Ctr Posttraumat Stress Disorder PTSD, Boston, MA USA. RP Mechanic, MB (reprint author), Calif State Univ Fullerton, Fullerton, CA 92634 USA. FU NIMH NIH HHS [1-R01-MH55542, R01 MH055542, R01 MH055542-03] NR 37 TC 9 Z9 9 U1 3 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-8012 J9 VIOLENCE AGAINST WOM JI Violence Against Women PD OCT PY 2008 VL 14 IS 10 BP 1148 EP 1165 DI 10.1177/1077801208323792 PG 18 WC Women's Studies SC Women's Studies GA 349UX UT WOS:000259309900004 PM 18757347 ER PT J AU Velmahos, GC AF Velmahos, George C. TI Surgical education around the world SO WORLD JOURNAL OF SURGERY LA English DT Editorial Material C1 [Velmahos, George C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Velmahos, George C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD OCT PY 2008 VL 32 IS 10 BP 2133 EP 2133 DI 10.1007/s00268-008-9637-2 PG 1 WC Surgery SC Surgery GA 347LO UT WOS:000259143300001 PM 18543026 ER PT J AU Spaniolas, K Velmahos, GC Alam, HB de Moya, M Tabbara, M Sailhamer, E AF Spaniolas, Konstantinos Velmahos, George C. Alam, Hasan B. de Moya, Marc Tabbara, Malek Sailhamer, Elizabeth TI Does improved detection of blunt vertebral artery injuries lead to improved outcomes? Analysis of the National Trauma Data Bank (R) SO WORLD JOURNAL OF SURGERY LA English DT Article ID CERVICAL-SPINE TRAUMA; CEREBROVASCULAR INJURIES; FOLLOW-UP; DIAGNOSIS; STENTS; NECK AB The rate of blunt vertebral artery (BVI) has increased in institutions using aggressive screening protocols. It is unclear whether earlier diagnosis and therapy have improved outcomes. Our goal was to estimate the national incidence of BVI and BVI-related stroke (BVI-S), and report on the functional outcome of patients with this diagnosis. The annual rates of BVI and BVI-S were estimated by using the National Trauma Data Bank (NTDB (R)) from 2001 to 2005. The functional outcome was evaluated by the modified functional independence measure (FIM) score (range, 3-12). A total of 574 patients with BVI were identified among the 761,385 blunt trauma admissions (0.075% overall incidence). BVI-S was diagnosed in 12% of patients with BVI and no associated blunt carotid injury. The FIM on discharge was 9.62 +/- 2.78 (range, 3-12), and 49% of the patients showed complete functional independence. Overall mortality was 8%. The annual incidence showed a steady increase from 0.053% in 2001 to 0.1% in 2005 (p < 0.001). No difference in annual BVI-S and complete functional independence was observed. As a result of increased awareness, the nation-wide rate of detection of BVI has doubled in recent years. However, BVI-S rates and functional outcome have not improved, raising questions about the available treatment protocols. C1 [Spaniolas, Konstantinos; Velmahos, George C.; Alam, Hasan B.; de Moya, Marc; Tabbara, Malek; Sailhamer, Elizabeth] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Spaniolas, Konstantinos; Velmahos, George C.; Alam, Hasan B.; de Moya, Marc; Tabbara, Malek; Sailhamer, Elizabeth] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org OI Tabbara, Malek/0000-0003-1046-7803 NR 20 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD OCT PY 2008 VL 32 IS 10 BP 2190 EP 2194 DI 10.1007/s00268-008-9687-5 PG 5 WC Surgery SC Surgery GA 347LO UT WOS:000259143300012 PM 18648873 ER PT J AU Williams, SG Zietman, AL AF Williams, Scott G. Zietman, Anthony L. TI Does radical treatment have a role in the management of low-risk prostate cancer? The place for brachytherapy and external beam radiotherapy SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Prostate cancer; Radiotherapy; Brachytherapy ID DOSE-RATE BRACHYTHERAPY; QUALITY-OF-LIFE; ANDROGEN DEPRIVATION THERAPY; MODULATED RADIATION-THERAPY; RANDOMIZED CONTROLLED-TRIAL; IMAGE-GUIDED RADIOTHERAPY; PERINEURAL INVASION; URINARY MORBIDITY; ALPHA/BETA RATIO; CONFORMAL RADIOTHERAPY AB A number of forms of radiation therapy are now commonly used for the treatment of low-risk prostate cancer (LRPCa). The tumour control rates are typically excellent, and the risk of death from prostate cancer very low regardless of the treatment modality. This is despite there being a paucity of prospective evidence with which to guide the radiation oncologist in this particular disease subtype. Much of the decision-making will fall back to evidence extrapolated from much more advanced or high-grade malignancy, while our current understanding of comorbidities poorly illuminates the initial question of whether or not the patient requires radical treatment at all. The number of variables in the treatment selection algorithm continues to increase, with a virtually unending array of treatment options when one combines the available variations in radiation modality, technique, dose and dose fractionation. All treatment is associated with a risk of toxicity, and there are substantial differences in the toxicity seen between the modalities. A number are strongly associated with preexisting conditions and can be seen as relative contraindications to either a specific radiation modality, or any treatment in general. This article aims to review data regarding LRPCa and radiotherapy outcomes, and highlight the potential challenges to improve this data in a planned manner. C1 [Williams, Scott G.] Peter MacCallum Canc Ctr, Div Radiat Oncol, Melbourne, Vic 8006, Australia. [Zietman, Anthony L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Williams, SG (reprint author), Peter MacCallum Canc Ctr, Div Radiat Oncol, Locked Bag 1 Abeckett St, Melbourne, Vic 8006, Australia. EM scott.williams@petermac.org NR 98 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 EI 1433-8726 J9 WORLD J UROL JI World J. Urol. PD OCT PY 2008 VL 26 IS 5 BP 447 EP 456 DI 10.1007/s00345-008-0305-9 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 363DP UT WOS:000260246400007 PM 18777126 ER PT J AU Germane, KL Ohi, R Goldberg, MB Spiller, BW AF Germane, Katherine L. Ohi, Ryoma Goldberg, Marcia B. Spiller, Benjamin W. TI Structural and functional studies indicate that Shigella VirA is not a protease and does not directly destabilize microtubules SO BIOCHEMISTRY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; ADHESION; INVASION; SEQUENCE; ESPG2; CELLS AB VirA, an essential virulence factor in Shigella disease pathogenesis, is involved in the uptake, motility, and cell-to-cell spread of Shigella organisms within the human host. These functions have been attributed to a VirA protease activity and a mechanism of microtubule destruction via tubulin degradation [Yoshida, S., et al. (2006) Science 314, 985-989]. We report functional and crystallographic data indicating a novel VirA structure that lacks these activities but highlights the homology to the EspG virulence factor of pathogenic Escherichia coli. C1 [Germane, Katherine L.; Ohi, Ryoma; Spiller, Benjamin W.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Germane, Katherine L.; Ohi, Ryoma; Spiller, Benjamin W.] Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA. [Germane, Katherine L.; Ohi, Ryoma; Spiller, Benjamin W.] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA. [Goldberg, Marcia B.] Massachusetts Gen Hosp, Cambridge, MA 02139 USA. [Goldberg, Marcia B.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. RP Spiller, BW (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, 461 Preston Res Bldg,2220 Pierce Ave, Nashville, TN 37232 USA. EM benjamin.spiller@vanderbilt.edu OI germane, katherine/0000-0002-5191-2670 FU NIDDK NIH HHS [P30 DK058404]; NIGMS NIH HHS [T32 GM008320] NR 18 TC 22 Z9 23 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 30 PY 2008 VL 47 IS 39 BP 10241 EP 10243 DI 10.1021/bi801533k PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 351UC UT WOS:000259450400001 PM 18763811 ER PT J AU Mi, LZ Grey, MJ Nishida, N Walz, T Lu, CF Springer, TA AF Mi, Li-Zhi Grey, Michael J. Nishida, Noritaka Walz, Thomas Lu, Chafen Springer, Timothy A. TI Functional and structural stability of the epidermal growth factor receptor in detergent micelles and phospholipid nanodiscs SO BIOCHEMISTRY LA English DT Article ID INTEGRAL MEMBRANE-PROTEINS; ERBB RECEPTORS; EGF RECEPTOR; TRANSMEMBRANE DOMAINS; EXTRACELLULAR DOMAIN; BILAYER NANODISCS; CRYSTAL-STRUCTURE; TYROSINE KINASES; PLASMA-MEMBRANE; C ACTIVATION AB Cellular signaling mediated by the epidermal growth factor receptor (EGFR or ErbB) family of receptor tyrosine kinases plays an important role in regulating normal and oncogenic cellular physiology. While structures of isolated EGFR extracellular domains and intracellular protein tyrosine kinase domains have suggested mechanisms for growth factor-mediated receptor dimerization and allosteric kinase domain activation, understanding how the transmembrane and juxtamembrane domains contribute to transmembrane signaling requires structural studies on intact receptor molecules. In this report, recombinant EGFR constructs containing the extracellular, transmembrane, juxtamembrane, and kinase domains are overexpressed and purified from human embryonic kidney 293 cell cultures. The oligomerization state, overall structure, and functional stability of the purified EGF-bound receptor are characterized in detergent micelles and phospholipid bilayers. In the presence of EGF, catalytically active EGFR dimers can be isolated by gel filtration in dodecyl maltoside. Visualization of the dimeric species by negative stain electron microscopy and single particle averaging reveals an overall structure of the extracellular domain that is similar to previously published crystal structures and is consistent with the C-termini of domain IV being juxtaposed against one another as they enter the transmembrane domain. Although detergent-soluble preparations of EGFR are stable as dimers in the presence of EGF, they exhibit differential functional stability in Triton X-100 versus dodecyl maltoside. Furthermore, the kinase activity can be significantly stabilized by reconstituting purified EGF-bound EGFR dimers in phospholipid nanodiscs or vesicles, suggesting that the environment around the hydrophobic transmembrane and amphipathic juxtamembrane domains is important for stabilizing the tyrosine kinase activity in vitro. C1 [Mi, Li-Zhi; Grey, Michael J.; Nishida, Noritaka; Lu, Chafen; Springer, Timothy A.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Mi, Li-Zhi; Grey, Michael J.; Nishida, Noritaka; Lu, Chafen; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. EM springer@idi.harvard.edu RI Nishida, Noritaka/E-7087-2010; Mi, Li-Zhi/B-1371-2016 OI Mi, Li-Zhi/0000-0001-9907-5245 FU National Institutes of Health; Guggenheim Foundation; American Cancer Society FX This work has been supported by grants from the National Institutes of Health and the Guggenheim Foundation awarded to T.A.S. and a postdoctoral fellowship from the American Cancer Society awarded to M.J.G. The molecular electron microscopy facility at Harvard Medical School was established with a generous donation from the Giovanni Armenise Harvard Center for Structural Biology and is maintained by funds from the National Institutes of Health awarded to Stephen C. Harrison. NR 46 TC 46 Z9 46 U1 4 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 30 PY 2008 VL 47 IS 39 BP 10314 EP 10323 DI 10.1021/bi801006s PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 351UC UT WOS:000259450400010 PM 18771282 ER PT J AU Troisi, R Hoover, RN Thadhani, R Hsieh, CC Sluss, P Ballard-Barbash, R Potischman, N AF Troisi, R. Hoover, R. N. Thadhani, R. Hsieh, C-C Sluss, P. Ballard-Barbash, R. Potischman, N. TI Maternal, prenatal and perinatal characteristics and first trimester maternal serum hormone concentrations SO BRITISH JOURNAL OF CANCER LA English DT Article DE hormones; birth weight; maternal age; parity; smoking ID BREAST-CANCER; BIRTH-WEIGHT; PREGNANCY ESTRIOL; BINDING GLOBULIN; UNITED-STATES; ETHNIC-GROUPS; RISK; ESTRADIOL; AGE; PROGESTERONE AB In uncomplicated pregnancies, first trimester androgen, oestrogen and prolactin concentrations were higher in nulliparous (n = 160) than parous (n = 260) mothers. Androgens and estrogens were higher in younger than older mothers. These data are consistent with elevated hormone concentrations mediating the breast cancer protection from a first pregnancy and pregnancies occurring at younger ages. C1 [Troisi, R.; Hoover, R. N.] Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, Rockville, MD 20892 USA. [Thadhani, R.; Sluss, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hsieh, C-C] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Ballard-Barbash, R.; Potischman, N.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD 20892 USA. RP Troisi, R (reprint author), Dartmouth Hitchcock Med Ctr, Room 854,7297 Rubin Bldg,1 Med Ctr Dr, Lebanon, NH 03756 USA. EM troisir@mail.nih.gov FU Divisions of Cancer Epidemiology and Genetics and Cancer Control and Population Sciences; National Cancer Institute; National Institutes of Health; US Department of Health and Human Services; HD [39223] FX The Divisions of Cancer Epidemiology and Genetics and Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services provided funding for the hormone assays, data analysis and article preparation. HD 39223 provided funding for the collection of original data. NR 26 TC 22 Z9 22 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 30 PY 2008 VL 99 IS 7 BP 1161 EP 1164 DI 10.1038/sj.bjc.6604639 PG 4 WC Oncology SC Oncology GA 355AS UT WOS:000259681600025 PM 18766187 ER PT J AU Danielyan, K Ganguly, K Ding, BS Atochin, D Zaitsev, S Murciano, JC Huang, PL Kasner, SE Cines, DB Muzykantov, VR AF Danielyan, Kristina Ganguly, Kumkum Ding, Bi-Sen Atochin, Dmitriy Zaitsev, Sergei Murciano, Juan-Carlos Huang, Paul L. Kasner, Scott E. Cines, Douglas B. Muzykantov, Vladimir R. TI Cerebrovascular thromboprophylaxis in mice by erythrocyte-coupled tissue-type plasminogen activator SO CIRCULATION LA English DT Article DE erythrocytes; fibrinolysis; plasminogen activators; stroke ID FOCAL CEREBRAL-ISCHEMIA; ARTERY-BYPASS-SURGERY; EMBOLIC STROKE; PROPHYLACTIC FIBRINOLYSIS; PERIOPERATIVE MANAGEMENT; MYOCARDIAL-INFARCTION; THERAPEUTIC WINDOW; ADJUVANT TREATMENT; RAT MODEL; TPA AB Background - Cerebrovascular thrombosis is a major source of morbidity and mortality after surgery, but thromboprophylaxis in this setting is limited because of the formidable risk of perioperative bleeding. Thrombolytics (eg, tissue-type plasminogen activator [tPA]) cannot be used prophylactically in this high-risk setting because of their short duration of action and risk of causing hemorrhage and central nervous system damage. We found that coupling tPA to carrier red blood cells (RBCs) prolongs and localizes tPA activity within the bloodstream and converts it into a thromboprophylactic agent, RBC/tPA. To evaluate the utility of this new approach for preventing cerebrovascular thrombosis, we examined the effect of RBC/tPA in animal models of cerebrovascular thromboembolism and ischemia. Methods and Results - Preformed fibrin microemboli were injected into the middle carotid artery of mice, occluding downstream perfusion and causing severe infarction and 50% mortality within 48 hours. Preinjected RBC/tPA rapidly lysed nascent cerebral thromboemboli, providing rapid, durable reperfusion and reducing morbidity and mortality. These beneficial effects were not achieved by preinjection of tPA, even at a 10-fold higher dose, which increased mortality from 50% to 90% by 10 hours after embolization. RBC/tPA injected 10 minutes after tail amputation to simulate postsurgical hemostasis did not cause bleeding from the wound, whereas soluble tPA caused profuse bleeding. RBC/tPA neither aggravated brain damage caused by focal ischemia in a filament model of middle carotid artery occlusion nor caused postthrombotic hemorrhage in hypertensive rats. Conclusions - These results suggest a potential RBC/tPA utility as thromboprophylaxis in patients who are at risk for acute cerebrovascular thromboembolism. C1 [Danielyan, Kristina; Ding, Bi-Sen; Zaitsev, Sergei; Muzykantov, Vladimir R.] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. [Kasner, Scott E.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Cines, Douglas B.] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. [Ganguly, Kumkum] Los Alamos Natl Lab, Los Alamos, NM USA. [Atochin, Dmitriy; Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Murciano, Juan-Carlos] Ctr Nacl Invest Cardiovasc, Madrid, Spain. RP Muzykantov, VR (reprint author), Univ Penn, Dept Pharmacol, 1 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM muzykant@mail.med.upenn.edu RI Kasner, Scott/C-6109-2011; Atochin, Dmitriy/Q-3150-2016 FU National Institutes of Health [RO1 HL66442, HL090697, HL076406, CA83121, HL076206, HL82545]; American Heart Association Bugher-Stroke Award; American Heart Association predoctoral fellowship; American Heart Association Scientist Development Award; Institute for Translational Medicine and Therapeutics; University of Pennsylvania; Fondo de investigacion Sanitaria [PI 040961]; Ramon y Cajal Foundation Awards FX This study was supported by National Institutes of Health grants RO1 HL66442, HL090697, HL076406, CA83121, HL076206, and HL82545 and American Heart Association Bugher-Stroke Award (Dr Muzykantov), American Heart Association predoctoral fellowship (B.-S. Ding), American Heart Association Scientist Development Award (Dr Zaitsev), and an award from the Institute for Translational Medicine and Therapeutics, University of Pennsylvania (Dr Cines), and Fondo de investigacion Sanitaria grant PI 040961 and Ramon y Cajal Foundation Awards (Dr Murciano). NR 48 TC 38 Z9 39 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 SEP 30 PY 2008 VL 118 IS 14 BP 1442 EP 1449 DI 10.1161/CIRCULATIONAHA.107.750257 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 354OE UT WOS:000259648100007 PM 18794394 ER PT J AU Hung, J Solis, J Guerrero, JL Braithwaite, GJC Muratoglu, OK Chaput, M Fernandez-Friera, L Handschumacher, MD Wedeen, VJ Houser, S Vlahakes, GJ Levine, RA AF Hung, Judy Solis, Jorge Guerrero, J. Luis Braithwaite, Gavin J. C. Muratoglu, Orhun K. Chaput, Miguel Fernandez-Friera, Leticia Handschumacher, Mark D. Wedeen, Van J. Houser, Stuart Vlahakes, Gus J. Levine, Robert A. TI A novel approach for reducing ischemic mitral regurgitation by injection of a polymer to reverse remodel and reposition displaced papillary muscles SO CIRCULATION LA English DT Article; Proceedings Paper CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc DE coronary artery disease; left ventricular remodeling; mitral regurgitation ID 3-DIMENSIONAL ECHOCARDIOGRAPHY; VALVULAR REGURGITATION; MYOCARDIAL-INFARCTION; CELL TRANSPLANTATION; COLLAGEN INJECTION; IN-VIVO; REPAIR; RECONSTRUCTION; ANNULOPLASTY; REPLACEMENT AB Background-Ischemic mitral regurgitation (MR) relates to displacement of the papillary muscles from ischemic ventricular distortion. We tested the hypothesis that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) polymer, a biologically inert biomaterial that has been specially formulated to produce an encapsulated, stable, resilient gel once injected into the myocardium. The purpose is to materially support the infarcted myocardium while at the same time repositioning the papillary muscles that become apically tethered in MR. Methods and Results-Nine sheep underwent ligation of circumflex branches to produce acute ischemic MR. PVA polymer was then injected by echo guidance into the myocardium underlying the infarcted papillary muscle. Hemodynamic data, left ventricular ejection fraction, elastance, tau (relaxation constant), left ventricular stiffness coefficient, and 2-dimensional and 3-dimensional echocardiograms were obtained post-MR and post-PVA injection. One animal died after coronary ligation and 2 did not develop MR. In the remaining 6, moderate MR developed. With PVA injection, the MR decreased significantly from moderate to trace-mild (vena contracta: 5 +/- 0.4 mm versus 2 +/- 0.7 mm, post-MR versus post-PVA injection; P < 0.0001). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (27 +/- 4 to 24 +/- 4 mm, post-MR versus post-PVA, P < 0.001). Importantly, PVA injection was not associated with significant decreases in left ventricular ejection fraction (43 +/- 6% versus 37 +/- 4%, post-MR versus post-PVA, P=nonsignificant), elastance (3.5 +/- 1.4 versus 2.9 +/- 1.3; post-MR versus post-PVA injection, P=nonsignificant). Measures of left ventricular diastolic function, tau (100 +/- 51 ms to 84 +/- 37 ms, post-MR versus post-PVA; P=nonsignificant), and left ventricular stiffness coefficient (0.18 +/- 0.12 versus 0.14 +/- 0.08, post-MR versus post-PVA; P=nonsignificant) did not increase post-PVA. Conclusions-PVA polymer injection resulted in acute reverse remodeling of the ventricle with papillary muscle repositioning to decrease MR. This was not associated with an adverse effect on left ventricular systolic and diastolic function. This new approach to alter pathological anatomy after infarction may offer an alternative strategy for relieving ischemic MR by correcting the position of the affected papillary muscle, thus relieving apical tethering. C1 [Hung, Judy] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Braithwaite, Gavin J. C.] Cambridge Polymer Inc, Boston, MA USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 256,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org RI Fernandez Friera, Leticia /E-9931-2015; OI Fernandez Friera, Leticia /0000-0002-4237-2166; Braithwaite, Gavin/0000-0002-6239-0046 FU NHLBI NIH HHS [R01 HL038176-14, K24 HL067434, K24 HL067434-07, K24 HL67434, R01 HL038176]; NIBIB NIH HHS [R21 EB005294, R21 EB005294-02]; PHS HHS [R01 038176] NR 45 TC 18 Z9 18 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 SEP 30 PY 2008 VL 118 IS 14 SU 1 BP S263 EP S269 DI 10.1161/CIRCULATIONAHA.107.756502 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 354OJ UT WOS:000259648600038 PM 18824765 ER PT J AU Jensen, MO Jensen, H Smerup, M Levine, RA Yoganathan, AP Nygaard, H Hasenkam, JM Nielsen, SL AF Jensen, Morten O. Jensen, Henrik Smerup, Morten Levine, Robert A. Yoganathan, Ajit P. Nygaard, Hans Hasenkam, J. Michael Nielsen, Sten L. TI Saddle-shaped mitral valve annuloplasty rings experience lower forces compared with flat rings SO CIRCULATION LA English DT Article; Proceedings Paper CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc DE mitral valve; mitral annuloplasty rings; heart valve diseases ID ANNULAR DILATATION; IN-VITRO; REGURGITATION; MODEL; SELECTION; PIGS AB Background-New insight into the 3D dynamic behavior of the mitral valve has prompted a reevaluation of annuloplasty ring designs. Force balance analysis indicates correlation between annulus forces and stresses in leaflets and chords. Improving this stress distribution can intuitively enhance the durability of mitral valve repair. We tested the hypothesis that saddle-shaped annuloplasty rings have superior uniform systolic force distribution compared with a nonuniform force distribution in flat annuloplasty rings. Methods and Results-Sixteen 80-kg pigs had a flat (n = 8) or saddle-shaped (n = 8) mitral annuloplasty ring implanted. Mitral annulus 3D dynamic geometry was obtained with sonomicrometry before ring insertion. Strain gauges mounted on dedicated D-shaped rigid flat and saddle-shaped annuloplasty rings provided the intraoperative force distribution perpendicular to the annular plane. Average systolic annular height to commissural width ratio before ring implantation was 14.0% +/- 1.6%. After flat and saddle shaped ring implantation, the annulus was fixed in the diastolic (9.0% +/- 1.0%) and systolic (14.3% +/- 1.3%) configuration, respectively (P < 0.01). Force accumulation was seen from the anterior (0.72N +/- 0.14N) and commissural annular segments (average 1.38N +/- 0.27N) of the flat rings. In these segments, the difference between the 2 types of rings was statistically significant (P < 0.05). The saddle-shaped annuloplasty rings did not experience forces statistically significantly larger than zero in any annular segments. Conclusions-Saddle-shaped annuloplasty rings provide superior uniform annular force distribution compared to flat rings and appear to represent a configuration that minimizes out-of-plane forces that could potentially be transmitted to leaflets and chords. This may have important implications for annuloplasty ring selections. C1 [Jensen, Morten O.; Jensen, Henrik; Smerup, Morten; Nygaard, Hans; Hasenkam, J. Michael; Nielsen, Sten L.] Aarhus Univ Hosp, Inst Clin Med, Dept Cardiothorac & Vasc Surg, DK-8200 Aarhus, Denmark. [Jensen, Morten O.; Nygaard, Hans] Engn Coll Aarhus, Dept Biomed Engn, Aarhus, Denmark. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Yoganathan, Ajit P.] Georgia Inst Technol, Wallace H Coulter Sch Biomed Engn, Atlanta, GA 30332 USA. [Yoganathan, Ajit P.] Emory Univ, Atlanta, GA 30322 USA. RP Jensen, MO (reprint author), Aarhus Univ Hosp, Inst Clin Med, Dept Cardiothorac & Vasc Surg, DK-8200 Aarhus, Denmark. EM morten.jensen@ki.au.dk FU NHLBI NIH HHS [HL 52009, K24 HL67434] NR 21 TC 53 Z9 54 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 SEP 30 PY 2008 VL 118 IS 14 SU 1 BP S250 EP S255 DI 10.1161/CIRCULATIONAHA.107.746776 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 354OJ UT WOS:000259648600036 PM 18824763 ER PT J AU Spinale, FG Koval, CN Deschamps, AM Stroud, RE Ikonomidis, JS AF Spinale, Francis G. Koval, Christine N. Deschamps, Anne M. Stroud, Robert E. Ikonomidis, John S. TI Dynamic changes in matrix metalloprotienase activity within the human myocardial interstitium during myocardial arrest and reperfusion SO CIRCULATION LA English DT Article DE microdialysis; cardiac surgery; fluorogenic substrates; extracellular matrix ID PREVENTS CARDIAC RUPTURE; METALLOPROTEINASE ACTIVITY; CARDIOPULMONARY BYPASS; FLUOROGENIC SUBSTRATE; HUMAN HEART; INFARCTION; ISCHEMIA; INHIBITION; MATRIX-METALLOPROTEINASE-9; ACTIVATION AB Background-Past studies have clearly established that matrix metalloproteinases (MMPs) contribute to adverse myocardial remodeling with ischemia and reperfusion. However, these studies measured MMP levels in extracted samples, and therefore whether and to what degree actual changes in interstitial MMP activity occur within the human myocardium in the context of ischemia/reperfusion remained unknown. Methods and Results-The present study directly quantified MMP interstitial activity within the myocardium of patients (n=14) undergoing elective cardiac surgery during steady-state conditions, as well as during and following an obligatory period of myocardial arrest and reperfusion achieved by cardiopulmonary bypass. Interstitial MMP activity was continuously monitored using a validated MMP fluorogenic substrate, a microdialysis system placed within the myocardium, and in-line fluorescent detection system. MMP activity, as measured by fluorescent emission, reached a stable steady state level by 10 minutes after deployment of the microdialysis system. During initiation of cardiopulmonary bypass, MMP activity increased by 20% from baseline values ( P<0.05), and then rapidly fell with cardiac arrest and longer periods of cardiopulmonary bypass. However, with restoration of myocardial blood flow and separation from cardiopulmonary bypass, MMP interstitial activity increased by over 30% from baseline ( P<0.05). Conclusions-The present study directly demonstrated that MMP proteolytic activity exists within the human myocardial interstitium and is a dynamic process under conditions such as myocardial arrest and reperfusion. C1 [Spinale, Francis G.; Koval, Christine N.; Deschamps, Anne M.; Stroud, Robert E.] Med Univ S Carolina, Strom Thurmond Res Ctr, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Spinale, Francis G.; Ikonomidis, John S.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Strom Thurmond Res Ctr, Div Cardiothorac Surg, 114 Doughty St,Suite 625, Charleston, SC 29425 USA. EM wilburnm@musc.edu OI Deschamps, Anne/0000-0001-7415-1408 FU NIH [HL59165, PO1 HL48788-08]; Veterans' Affairs Health Administration FX This study was supported by NIH grants HL59165, PO1 HL48788-08 and a Merit Award from the Veterans' Affairs Health Administration. NR 32 TC 22 Z9 22 U1 1 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 SEP 30 PY 2008 VL 118 IS 14 SU 1 BP S16 EP S23 DI 10.1161/CIRCULATIONAHA.108.786640 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 354OJ UT WOS:000259648600003 PM 18824748 ER PT J AU Asaad, WF Eskandar, EN AF Asaad, Wael F. Eskandar, Emad N. TI A flexible software tool for temporally-precise behavioral control in Matlab SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Neurophysiology; Psychophysics; Matlab; Behavioral control; Software; Cognition; Human; Monkey ID PSYCHOPHYSICS AB Systems and cognitive neuroscience depend on carefully designed and precisely implemented behavioral tasks to elicit the neural phenomena of interest. To facilitate this process, we have developed a software system that allows for the straightforward coding and temporally-reliable execution of these tasks in Matlab. We find that, in most cases, millisecond accuracy is attainable, and those instances in which it is not are usually related to predictable, programmed events. In this report, we describe the design of our system, benchmark its performance in a real-world setting, and describe some key features. (C) 2008 Elsevier B.V. All rights reserved. C1 [Asaad, Wael F.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Asaad, Wael F.; Eskandar, Emad N.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Asaad, WF (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Edwards Bldg,Room 426,55 Fruit St, Boston, MA 02114 USA. EM wfasaad@alum.mit.edu RI Asaad, Wael/I-8485-2012 OI Asaad, Wael/0000-0003-4406-9096 FU Massachusetts Biomedical Research Council; NEI [1R01DA026297]; NSF [IOB 0645886]; HHMI FX The authors thank David Freedman, Tim Buschman, Camillo Padoa-Schioppa, Valerie Yorgan, Markus Siegel, and John Gale for contributions to the software, beta testing, and helpful discussions. We also thank Jeffrey Perry for making the low-level graphic drivers publicly available and for helpful advice regarding their implementation. Anne-Marie Amacher, Ming Cheng, Jason Gerrard, Rollin Hu, Earl Miller, Andrew Mitz and Ziv Williams are appreciated for offering useful ideas for program testing and execution. We are indebted to the CORTEX development team (http://www.cortex.salk.edu) for their widely used behavioral control software, which provided all initial framework for the creation of our software. Funding was provided by a Tosteson Fellowship from the Massachusetts Biomedical Research Council to WFA and NEI grant 1R01DA026297, NSF IOB 0645886 and the HHMI to ENE. NR 11 TC 35 Z9 35 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD SEP 30 PY 2008 VL 174 IS 2 BP 245 EP 258 DI 10.1016/j.jneumeth.2008.07.014 PG 14 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 358GR UT WOS:000259905600011 PM 18706928 ER PT J AU Sundelof, J Arnlov, J Ingelsson, E Sundstrom, J Basu, S Zethelius, B Larsson, A Irizarry, MC Giedraitis, V Ronnemaa, E Degerman-Gunnarsson, M Hyman, BT Basun, H Kilander, L Lannfelt, L AF Sundelof, J. Arnlov, J. Ingelsson, E. Sundstrom, J. Basu, S. Zethelius, B. Larsson, A. Irizarry, M. C. Giedraitis, V. Ronnemaa, E. Degerman-Gunnarsson, M. Hyman, B. T. Basun, H. Kilander, L. Lannfelt, L. TI Serum cystatin C and the risk of Alzheimer disease in elderly men SO NEUROLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; CHRONIC KIDNEY-DISEASE; AMYLOID-BETA PROTEIN; CARDIOVASCULAR EVENTS; GENE; DEMENTIA; ASSOCIATION; BRAIN; PATHOGENESIS AB Background: Multiple lines of research suggest that increased cystatin C activity in the brain protects against the development of Alzheimer disease (AD). Methods: Serum cystatin C levels were analyzed at two examinations of the Uppsala Longitudinal Study of Adult Men, a longitudinal, community-based study of elderly men (age 70 years, n = 1,153 and age 77 years, n = 761, a subset of the age 70 examination). Cox regressions were used to examine associations between serum cystatin C and incident AD. AD cases were identified by cognitive screening and comprehensive medical chart review in all subjects. Results: On follow-up (median 11.3 years), 82 subjects developed AD. At age 70 years, lower cystatin C was associated with higher risk of AD independently of age, APOE4 genotype, glomerular filtration rate, diabetes, hypertension, stroke, cholesterol, body mass index, smoking, education level, and plasma amyloid-beta protein 40 and 42 levels (hazard ratio [HR] for lowest [< 1.12 mu mol/L] vs highest [> 1.30 mu mol/L] tertile = 2.67, 95% CI 1.22-5.83, p < 0.02). The results were similar at age 77 years (43 participants developed AD during follow-up). Furthermore, a 0.1 mu mol/L decrease of cystatin C between ages 70 and 77 years was associated with a 29% higher risk of incident AD (HR 1.29, 95% CI 1.03-1.63, p < 0.03). Conclusions: Low levels of serum cystatin C precede clinically manifest Alzheimer disease (AD) in elderly men free of dementia at baseline and may be a marker of future risk of AD. These findings strengthen the evidence for a role for cystatin C in the development of clinical AD. C1 [Sundelof, J.; Arnlov, J.; Ingelsson, E.; Basu, S.; Zethelius, B.; Giedraitis, V.; Ronnemaa, E.; Degerman-Gunnarsson, M.; Kilander, L.; Lannfelt, L.] Uppsala Univ, Dept Publ Hlth Geriatr, S-75185 Uppsala, Sweden. [Sundstrom, J.; Larsson, A.] Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden. [Irizarry, M. C.; Hyman, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Basun, H.] Astra Zeneca, Sodertalje, Sweden. RP Sundelof, J (reprint author), Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala Sci Pk,Dag Hammarskolds Vag 14B, S-75185 Uppsala, Sweden. EM johan.sundelof@pubcare.uu.se RI Arnlov, Johan/N-9886-2013; Sundstrom, Johan/A-6286-2009 OI Sundstrom, Johan/0000-0003-2247-8454 FU The Swedish Research Council [2003-5546, 2006-6555]; Swedish Heart-Lung Foundation; Swedish Lions Research Foundation; NIH [1T32NS048005-01, AG05134]; AFAR Beeson Award; J.D. French Alzheimer's Foundation FX Supported by Wallenberg Consortium North, Hjarnfonden, Bertil Hallstens forskningsstiftelse, Alzheimerfonden, The Swedish Research Council (2003-5546 and 2006-6555), Stiftelsen Gamla Tjanarinnor, Capios Forskningsstiftelse, Gun och Bertil Stohnes Forskningsstiftelse, Swedish Heart-Lung Foundation, Swedish Lions Research Foundation, Erik, Karin och Gosta Selanders Stiftelse, Loo och Hans Ostermans stiftelse, NIH 1T32NS048005-01, AG05134 (Massachusetts AD Research Center), AFAR Beeson Award (to M.C.I.), J.D. French Alzheimer's Foundation, and Astra Zeneca with an unrestricted grant. The funding sources did not play any 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. There are no conflicts of interest for any of the authors. NR 38 TC 37 Z9 38 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 30 PY 2008 VL 71 IS 14 BP 1072 EP 1079 DI 10.1212/01.wnl.0000326894.40353.93 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 354OO UT WOS:000259649100007 PM 18824671 ER PT J AU Blackburn, SD Shin, H Freeman, GJ Wherry, EJ AF Blackburn, Shawn D. Shin, Haina Freeman, Gordon J. Wherry, E. John TI Selective expansion of a subset of exhausted CD8 T cells by alpha PD-L1 blockade SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chronic infection; lymphocytic choriomeningitis virus; T cell exhaustion; PD-1; T cell memory ID CHRONIC VIRAL-INFECTION; PD-1 EXPRESSION; THERAPEUTIC VACCINATION; DISEASE PROGRESSION; UP-REGULATION; VIRUS; DYSFUNCTION; IMMUNITY; ANTIGEN; LIVER AB Programmed death-1 (PD-1) regulates T cell exhaustion during chronic infections. Blocking the PD-1: PD-ligand (PD-L) pathway reinvigorates exhausted CD8 T cells. Exactly how blocking PD-1: PD-L interactions improves T cell immunity, however, remains unclear. PD-1: PD-L blockade could reprogram all exhausted T cells to become antiviral effectors. Alternatively, this blockade might selectively expand a subset of exhausted T cells. We have identified two subpopulations of exhausted CD8 T cells during chronic viral infection in mice. One subset of exhausted CD8 T cells is rescued by alpha PD-L1 blockade, whereas the other subset appears more terminally differentiated and responds poorly to PD-1: PD-L blockade. Blocking PD-1: PD-L interactions reduces spontaneous apoptosis and enhances expansion and protective immunity of the rescuable subset, but not the more terminally differentiated subset of exhausted CD8 T cells. These results have implications for predicting clinical responses to PD-1-based therapeutic interventions and for understanding T cell dynamics during persisting infections. C1 [Blackburn, Shawn D.; Shin, Haina; Wherry, E. John] Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. [Freeman, Gordon J.] Dana Farber Canc Ctr, Dept Med Oncol, Boston, MA 02115 USA. RP Wherry, EJ (reprint author), Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. EM jwherry@wistar.org FU National Institutes of Health [AI071309, AI56299, HHSN 26620050030C]; Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health FX We thank Dan Barber, Dave Masopust, Kyong-Mi Chang, and the members of the Wherry laboratory for helpful discussions. This work was supported by National Institutes of Health Grants AI071309 (to E.J.W.), AI56299 (to G.J.F.), and HHSN 26620050030C (to E.J.W. and G.J.F.) and by the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health (to E.J.W.). NR 24 TC 123 Z9 127 U1 1 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 SEP 30 PY 2008 VL 105 IS 39 BP 15016 EP 15021 DI 10.1073/pnas.0801497105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 386WW UT WOS:000261914300035 PM 18809920 ER PT J AU Eikesdal, HP Sugimoto, H Birrane, G Maeshima, Y Cooke, VG Kieran, M Kalluri, R AF Eikesdal, Hans Petter Sugimoto, Hikaru Birrane, Gabriel Maeshima, Yohei Cooke, Vesselina G. Kieran, Mark Kalluri, Raghu TI Identification of amino acids essential for the antiangiogenic activity of tumstatin and its use in combination antitumor activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE angiogenesis; alpha v beta 3 integrin; bevacizumab; tumstatin peptide ID ALPHA(V)BETA(3) INTEGRIN; BASEMENT-MEMBRANE; CRYSTAL-STRUCTURE; BREAST-CANCER; GROWTH-FACTOR; IV COLLAGEN; ANGIOGENESIS; INHIBITOR; DOMAIN; ALPHA-V-BETA-3 AB Tumstatin is an angiogenesis inhibitor that binds to alpha v beta 3 integrin and suppresses tumor growth. Previous deletion mutagenesis studies identified a 25-aa fragment of tumstatin (tumstatin peptide) with in vitro antiangiogenic activity. Here, we demonstrate that systemic administration of this tumstatin peptide inhibits tumor growth and angiogenesis. Site-directed mutagenesis identified amino acids L, V, and D as essential for the antiangiogenic activity of tumstatin. The tumstatin peptide binds to alpha v beta 3 integrin on proliferating endothelial cells and localizes to select tumor endothelium in vivo. Using 3D molecular modeling, we identify a putative interaction interface for tumstatin peptide on alpha v beta 3 integrin. The antitumor activity of the tumstatin peptide, in combination with bevacizumab (anti-VEGF antibody), displays significant improvement in efficacy against human renal cell carcinoma xeno-grafts when compared with the single-agent use. Collectively, our results demonstrate that tumstatin peptide binds specifically to the tumor endothelium, and its antiangiogenic action is mediated by alpha v beta 3 integrin, and, in combination with an anti-VEGF antibody it exhibits enhanced tumor suppression of renal cell carcinoma. C1 [Eikesdal, Hans Petter; Sugimoto, Hikaru; Maeshima, Yohei; Cooke, Vesselina G.; Kalluri, Raghu] Beth Israel Deaconess Med Ctr, Dept Med, Div Matrix Biol, Boston, MA 02215 USA. [Birrane, Gabriel] Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02215 USA. [Birrane, Gabriel] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Kieran, Mark] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Kalluri, Raghu] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Kalluri, Raghu] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Kalluri, R (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Matrix Biol, Boston, MA 02215 USA. EM rkalluri@bidmc.harvard.edu RI Kalluri, Raghu/E-2677-2015; OI Birrane, Gabriel/0000-0002-1759-5499; Kalluri, Raghu/0000-0002-2190-547X; Kieran, Mark/0000-0003-2184-7692 FU NCI NIH HHS [CA12550]; NIAAA NIH HHS [AA13913, R01 AA013913]; NIDDK NIH HHS [DK55001, DK61688, DK62987, R01 DK055001, R01 DK061688, R01 DK062987] NR 28 TC 32 Z9 40 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 30 PY 2008 VL 105 IS 39 BP 15040 EP 15045 DI 10.1073/pnas.0807055105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 386WW UT WOS:000261914300039 PM 18818312 ER PT J AU Carp, SA Selb, J Fang, Q Moore, R Kopans, DB Rafferty, E Boas, DA AF Carp, S. A. Selb, J. Fang, Q. Moore, R. Kopans, D. B. Rafferty, E. Boas, D. A. TI Dynamic functional and mechanical response of breast tissue to compression SO OPTICS EXPRESS LA English DT Article ID DIFFUSE OPTICAL SPECTROSCOPY; POSITRON EMISSION TOMOGRAPHY; REGIONAL BLOOD-FLOW; SCATTERING MEDIA; NEOADJUVANT CHEMOTHERAPY; EXTERNAL PERTURBATIONS; CANCER; MAMMOGRAPHY; TUMORS; ARTERIAL AB Physiological tissue dynamics following breast compression offer new contrast mechanisms for evaluating breast health and disease with near infrared spectroscopy. We monitored the total hemoglobin concentration and hemoglobin oxygen saturation in 28 healthy female volunteers subject to repeated fractional mammographic compression. The compression induces a reduction in blood flow, in turn causing a reduction in hemoglobin oxygen saturation. At the same time, a two phase tissue viscoelastic relaxation results in a reduction and redistribution of pressure within the tissue and correspondingly modulates the tissue total hemoglobin concentration and oxygen saturation. We observed a strong correlation between the relaxing pressure and changes in the total hemoglobin concentration bearing evidence of the involvement of different vascular compartments. Consequently, we have developed a model that enables us to disentangle these effects and obtain robust estimates of the tissue oxygen consumption and blood flow. We obtain estimates of 1.9 +/- 1.3 mu mol/100mL/min for OC and 2.8 +/- 1.7 mL/100mL/min for blood flow, consistent with other published values. (c) 2008 Optical Society of America C1 [Carp, S. A.; Selb, J.; Fang, Q.; Boas, D. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Moore, R.; Kopans, D. B.; Rafferty, E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Carp, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM carp@nmr.mgh.harvard.edu FU NIH [R01-CA97305, U54-CA105480] FX We would like to acknowledge funding from NIH through grants R01-CA97305 and U54-CA105480. Also we would like to thank Dr. Solomon Diamond, Dr. Gregory Boverman, Dr. Dana Brooks and Dr. Eric Miller for useful discussions. NR 50 TC 32 Z9 32 U1 0 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD SEP 29 PY 2008 VL 16 IS 20 BP 16064 EP 16078 DI 10.1364/OE.16.016064 PG 15 WC Optics SC Optics GA 360XK UT WOS:000260091300081 PM 18825246 ER PT J AU Scarcelli, G Yun, SH AF Scarcelli, Giuliano Yun, Seok H. TI Entangled-photon coincidence fluorescence imaging SO OPTICS EXPRESS LA English DT Article AB We describe fluorescence imaging using the second-order correlation of entangled photon pairs. The proposed method is based on the principle that one photon of the pair carries information on where the other photon has been absorbed and has produced fluorescence in a sample. Because fluorescent molecules serve as "detectors" breaking the entanglement, multiply-scattered fluorescence photons within the sample do not cause image blur. We discuss experimental implementations. (c) 2008 Optical Society of America C1 [Scarcelli, Giuliano] Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 50 Blossom St, Boston, MA 02114 USA. EM syun@hms.harvard.edu OI scarcelli, giuliano/0000-0002-1736-077X FU NCI NIH HHS [R33 CA110130, R33 CA110130-01] NR 14 TC 6 Z9 6 U1 1 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD SEP 29 PY 2008 VL 16 IS 20 BP 16189 EP 16194 DI 10.1364/OE.16.016189 PG 6 WC Optics SC Optics GA 360XK UT WOS:000260091300092 PM 18825257 ER PT J AU Yu, CC Lau, C O'Donoghue, G Mirkovic, J McGee, S Galindo, L Elackattu, A Stier, E Grillone, G Badizadegan, K Dasari, RR Feld, MS AF Yu, Chung-Chieh Lau, Condon O'Donoghue, Geoff Mirkovic, Jelena McGee, Sasha Galindo, Luis Elackattu, Alphi Stier, Elizabeth Grillone, Gregory Badizadegan, Kamran Dasari, Ramachandra R. Feld, Michael S. TI Quantitative spectroscopic imaging for non-invasive early cancer detection SO OPTICS EXPRESS LA English DT Article ID DIFFUSE-REFLECTANCE SPECTROSCOPY; SQUAMOUS INTRAEPITHELIAL LESIONS; IN-VIVO DETECTION; FLUORESCENCE SPECTROSCOPY; LIGHT-SCATTERING; OPTICAL SPECTROSCOPY; BARRETTS-ESOPHAGUS; DIAGNOSIS; AUTOFLUORESCENCE; DYSPLASIA AB We report a fully quantitative spectroscopy imaging instrument for wide area detection of early cancer (dysplasia). This instrument provides quantitative maps of tissue biochemistry and morphology, making it a potentially powerful surveillance tool for objective early cancer detection. We describe the design, construction, calibration, and first clinical application of this new system. We demonstrate its accuracy using physical tissue models. We validate its diagnostic ability on a resected colon adenoma, and demonstrate feasibility of in vivo imaging in the oral cavity. (c) 2008 Optical Society of America C1 [Yu, Chung-Chieh; Lau, Condon; O'Donoghue, Geoff; Mirkovic, Jelena; McGee, Sasha; Galindo, Luis; Badizadegan, Kamran; Dasari, Ramachandra R.; Feld, Michael S.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. [Elackattu, Alphi; Grillone, Gregory] Boston Univ, Dept Otolaryngol Head & Neck Surg, Med Ctr, Boston, MA 02118 USA. [Stier, Elizabeth] Boston Univ, Dept Obstet & Gynecol, Med Ctr, Boston, MA 02118 USA. [Badizadegan, Kamran] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA 02114 USA. RP Yu, CC (reprint author), MIT, George R Harrison Spect Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM chungyu@mit.edu RI Mirkovic, Jelena/A-6253-2013; OI LAU, Condon/0000-0002-6569-5814 FU National Institute of Health [P41-RR02594, R01-CA97966] FX We gratefully acknowledge CCS America, Inc. (http://www.ccsamerica.com/) for their generous support in providing LED illumination system used in the QSI instrument. This research was conducted at the Massachusetts Institute of Technology Laser Biomedical Research Center and supported by the National Institute of Health (grants P41-RR02594 AND R01-CA97966). NR 35 TC 42 Z9 43 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD SEP 29 PY 2008 VL 16 IS 20 BP 16227 EP 16239 DI 10.1364/OE.16.016227 PG 13 WC Optics SC Optics GA 360XK UT WOS:000260091300097 PM 18825262 ER PT J AU Lue, N Choi, W Popescu, G Badizadegan, K Dasari, RR Feld, MS AF Lue, Niyom Choi, Wonshik Popescu, Gabriel Badizadegan, Kamran Dasari, Ramachandra R. Feld, Michael S. TI Synthetic aperture tomographic phase microscopy for 3D imaging of live cells in translational motion SO OPTICS EXPRESS LA English DT Article ID DIFFRACTION TOMOGRAPHY AB We present a technique for 3D imaging of live cells in translational motion without need of axial scanning of objective lens. A set of transmitted electric field images of cells at successive points of transverse translation is taken with a focused beam illumination. Based on Hyugens' principle, angular plane waves are synthesized from E-field images of a focused beam. For a set of synthesized angular plane waves, we apply a filtered back-projection algorithm and obtain 3D maps of refractive index of live cells. This technique, which we refer to as synthetic aperture tomographic phase microscopy, can potentially be combined with flow cytometry or microfluidic devices, and will enable high throughput acquisition of quantitative refractive index data from large numbers of cells. (c) 2008 Optical Society of America C1 [Lue, Niyom; Choi, Wonshik; Badizadegan, Kamran; Dasari, Ramachandra R.; Feld, Michael S.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. [Popescu, Gabriel] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. [Badizadegan, Kamran] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Badizadegan, Kamran] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Choi, W (reprint author), MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. EM wonshik@mit.edu FU National Center for Research Resources of the National Institutes of Health [P41-RR02594-18]; National Science Foundation [DBI-0754339]; Hamamatsu Corporation FX This work was funded by the National Center for Research Resources of the National Institutes of Health (P41-RR02594-18), the National Science Foundation (DBI-0754339) and Hamamatsu Corporation. NR 17 TC 26 Z9 27 U1 2 U2 13 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD SEP 29 PY 2008 VL 16 IS 20 BP 16240 EP 16246 DI 10.1364/OE.16.016240 PG 7 WC Optics SC Optics GA 360XK UT WOS:000260091300098 PM 18825263 ER PT J AU Sreejayan, N Yang, XP Palanichamy, K Dolence, K Ren, J AF Sreejayan, Nair Yang, Xiaoping Palanichamy, Kamalakannan Dolence, Kurt Ren, Jun TI Antioxidant properties of argpyrimidine SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE antioxidant; argpyrimidine; diabetes mellitus; free radical; neurodegenerative disease ID GLYCATION END-PRODUCTS; LIPID-PEROXIDATION; OXIDATIVE STRESS; METHYLGLYOXAL; PROTEINS; PHENOLS; INHIBITION; FLAVONOIDS; MECHANISM; CELLS AB Argpyrimidine, the product of non-enzymatic protein glycation by methylglyoxal, has been implicated in the pathophysiology of diabetes mellitus and neurodegenerative diseases. Chemically, argpyrimidine is a substituted pyrimidinol with structural features common to known antioxidants. The objective of this study was to investigate the antioxidant properties of argpyrimidine. Argpyrimidine was synthesized by mixing L-arginine with 3-acetoxypentane-2,4-dione under acidic conditions and purified by chromatography. Argpyrimidine inhibited lipid peroxidation of rat brain homogenates catalyzed by hydroxyl radicals, metal ions, and autooxidation in a concentration- and time-dependent manner. In addition, argpyrimidine scavenged superoxide anion, 1,1-diphenyl 2-picryl-hydrazyl-stable free radical, intracellular-hydrogen peroxide, and inhibited free-radical-mediated nicking of plasmid-DNA. Taken together, our data suggest that argpyrimidine has andoxidant properties and may therefore have biological relevance in pathophysiologies associated with diabetes mellitus and neurodegenerative diseases. (C) 2008 Elsevier B.V. All rights reserved. C1 [Sreejayan, Nair; Yang, Xiaoping; Palanichamy, Kamalakannan; Dolence, Kurt; Ren, Jun] Univ Wyoming, Div Pharmaceut Sci, Sch Pharm, Coll Hlth Sci, Laramie, WY 82071 USA. [Sreejayan, Nair; Yang, Xiaoping; Palanichamy, Kamalakannan; Dolence, Kurt; Ren, Jun] Univ Wyoming, Ctr Cardiovasc Res & Alternat Med, Laramie, WY 82071 USA. [Yang, Xiaoping] Univ Colorado, Div Cardiothorac Surg, Dept Surg, Sch Med, Denver, CO 80262 USA. [Yang, Xiaoping] Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. [Palanichamy, Kamalakannan] Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sreejayan, N (reprint author), Univ Wyoming, Div Pharmaceut Sci, Sch Pharm, Coll Hlth Sci, Laramie, WY 82071 USA. EM sreejay@uwyo.edu RI Palanichamy, Kamalakannan/E-3807-2011 FU ADA [AMDIAB47595] FX This work was supported by a grant from ADA (AMDIAB47595) to NS. The authors thank Ms. Virginia Cole for editing the manuscript and Ms. Maria Nolder Seeke for her assistance. NR 29 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD SEP 28 PY 2008 VL 593 IS 1-3 BP 30 EP 35 DI 10.1016/j.ejphar.2008.07.030 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 352PA UT WOS:000259508100005 PM 18692042 ER PT J AU Davies, JK Yuk, D Nadler, LM Guinan, EC AF Davies, Jeffrey K. Yuk, Dongin Nadler, Lee M. Guinan, Eva C. TI Induction of alloanergy in human donor T cells without loss of pathogen or tumor immunity SO TRANSPLANTATION LA English DT Article DE allogeneic hematopoietic stem cell transplantation; donor T cells; alloanergy; costimulatory blockade; graft-versus-host disease; immune reconstitution ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; HLA-IDENTICAL SIBLINGS; CFSE DYE DILUTION; HUMAN CYTOMEGALOVIRUS; SELECTIVE DEPLETION; CELLULAR-IMMUNITY; FLOW-CYTOMETRY; STEM-CELLS; LEUKEMIA AB Background. Human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic stein cell transplantation (HSCT) is limited by acute graft-versus-host disease (aGvHD). Nonselective T-cell depletion effectively prevents severe aGvHD but profoundly impairs donor-derived immune reconstitution, increasing infection and disease relapse. The strategy of induction of alloantigen-specific hyporesponsiveness ("alloanergization") in donor bone marrow by allostimulation with costimulatory blockade before haploidentical transplantation has demonstrated early promise in reducing severe aGvHD. However, the differential effect of alloanergization on CD4(+) and CD8(+) donor T-cell subsets and the degree to which beneficial pathogen- and tumor-immune responses are retained have not been extensively examined. Methods. We used an in vitro model of alloanergization by allostimulation of human donor T cells with irradiated unrelated recipient peripheral blood mononuclear cells and costimulatory blockade with humanized monoclonal anti-B7.1 and B7.2 antibodies. Residual alloresponses were assessed by proliferation (thymidine uptake, carboxyfluorescein diacetate succinimidyl ester dye dilution) and cytotoxicity assays. Retention of human herpes virus and tumor-associated antigen (TAA) -specific immunity was measured with HLA-class I-restricted pentamers, intracellular cytokine secretion, and CD107a assay using 5-color flow cytometry. Results. Alloanergization of HLA-mismatched donor T cells efficiently and selectively abrogated recipient-specific alloproliferation in both CD4(+) and CD8(+) cells while preserving functional CD4(+) and CD8+ immune responses to clinically important human herpes viruses and to the TAA WT 1. Conclusions. Retention of pathogen- and TAA-specific immunity after alloanergization demonstrates that this methodology, which is simple to apply, has potential to improve immune reconstitution while limiting alloreactivity after HLA-mismatched hematopoietic stem cell transplantation, and deserves additional evaluation in further human clinical trials. C1 [Davies, Jeffrey K.; Yuk, Dongin; Nadler, Lee M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Davies, Jeffrey K.; Nadler, Lee M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Guinan, Eva C.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Guinan, Eva C.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Davies, JK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jeff_davies@dfci.harvard.edu FU National Institutes of Health [U19 CA 100625] FX This research was funded in part by the National Institutes of Health grant U 19 CA 100625. NR 50 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD SEP 27 PY 2008 VL 86 IS 6 BP 854 EP 864 DI 10.1097/TP.0b013e3181861b6c PG 11 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 353US UT WOS:000259594600016 PM 18813111 ER PT J AU Jin, JF Hou, Q Mullen, TD Zeidan, YH Bielawski, J Kraveka, JM Bielawska, A Obeid, LM Hannun, YA Hsu, YT AF Jin, Junfei Hou, Qi Mullen, Thomas D. Zeidan, Youssef H. Bielawski, Jacek Kraveka, Jacqueline M. Bielawska, Alicja Obeid, Lina M. Hannun, Yusuf A. Hsu, Yi-Te TI Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced bax redistribution to mitochondria in NT-2 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERMEABILITY TRANSITION PORE; DELTA-MEDIATED PHOSPHORYLATION; CYTOCHROME-C RELEASE; ACID SPHINGOMYELINASE; CONFORMATIONAL-CHANGE; TNF-ALPHA; NEURONAL APOPTOSIS; CEREBRAL-ISCHEMIA; SIGNALS APOPTOSIS; HL-60 CELLS AB Ceramide functions as an important second messenger in apoptosis signaling pathways. In this report, we show that treatment of NT-2 neuronal precursor cells with hypoxia/reoxygenation (H/R) resulted in ceramide up-regulation. This elevation in ceramide was primarily due to the actions of acid sphingomyelinase and ceramide synthase LASS 5, demonstrating the action of the salvage pathway. Hypoxia/reoxygenation treatment led to Bax translocation from the cytoplasm to mitochondria and cytochrome c release from mitochondria. Down-regulation of either acid sphingomyelinase or LASS 5-attenuated ceramide accumulation and H/R-induced Bax translocation to mitochondria. Overall, we have demonstrated that ceramide upregulation following H/R is pertinent to Bax activation to promote cell death. C1 [Jin, Junfei; Hou, Qi; Zeidan, Youssef H.; Bielawski, Jacek; Bielawska, Alicja; Hannun, Yusuf A.; Hsu, Yi-Te] Med Univ S Carolina, Dept Biochem & Mol Biol, Div Hematol Oncol, Charleston, SC 29425 USA. [Mullen, Thomas D.; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Div Hematol Oncol, Charleston, SC 29425 USA. [Kraveka, Jacqueline M.] Med Univ S Carolina, Dept Pediat, Div Hematol Oncol, Charleston, SC 29425 USA. [Hou, Qi] Peking Union Med Coll, Inst Mat Med, Dept Pharmacol, Beijing 100050, Peoples R China. [Hou, Qi] Chinese Acad Med Sci, Beijing 100050, Peoples R China. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Hsu, YT (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Div Hematol Oncol, 173 Ashley Ave,POB 250509, Charleston, SC 29425 USA. EM hsuy@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [NS40932, CA97132] FX This work was supported, in whole or in part, by National Institutes of Health Grants NS40932 (to Y.-T. H.) and CA97132 ( to Y. A. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 71 TC 44 Z9 44 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 26 PY 2008 VL 283 IS 39 BP 26509 EP 26517 DI 10.1074/jbc.M801597200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 350GV UT WOS:000259341600027 PM 18676372 ER PT J AU Fischer, SEJ Butler, MD Pan, Q Ruvkun, G AF Fischer, Sylvia E. J. Butler, Maurice D. Pan, Qi Ruvkun, Gary TI Trans-splicing in C. elegans generates the negative RNAi regulator ERI-6/7 SO NATURE LA English DT Article ID CAENORHABDITIS-ELEGANS; GENETIC INTERFERENCE; DROSOPHILA; PROTEIN; ARGONAUTE; HELICASE; IDENTIFICATION; PATHWAYS; REVEALS; ENCODES AB Mutations that enhance the response to double- stranded RNA ( dsRNA) have revealed components of the RNA interference ( RNAi) pathway or related small RNA pathways. To explore these small RNA pathways, we screened for Caenorhabditis elegans mutants displaying an enhanced response to exogenous dsRNAs. Here we describe the isolation of mutations in two adjacent, divergently transcribed open reading frames ( eri-6 and eri-7) that fail to complement. eri-6 and eri- 7 produce separate pre- messenger RNAs ( pre- mRNAs) that are trans- spliced to form a functional mRNA, eri- 6/ 7. Trans- splicing of eri6/7 is mediated by a direct repeat that flanks the eri- 6 gene. Adenosine to inosine editing within untranslated regions of eri- 6 and eri- 7 pre- mRNAs reveals a double- stranded pre- mRNA intermediate, forming in the nucleus before splicing occurs. The ERI-6/7 protein is a superfamily I helicase that both negatively regulates the exogenous RNAi pathway and functions in an endogenous RNAi pathway. C1 [Fischer, Sylvia E. J.; Butler, Maurice D.; Pan, Qi; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Fischer, Sylvia E. J.; Butler, Maurice D.; Pan, Qi; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU Leukemia and Lymphoma Society; EMBO FX We thank: S. Kennedy for advice and initiating the enhanced RNAi screen; M. Finney for advice on advanced PCR; C. Zhang for mg441 Eri characterization; Y. Kohara, D. Thierry-Mieg and J. Thierry-Mieg for EST sequences and clones; the Mitani laboratory for deletion strains; the Caenorhabditis Genetics Center for strains; Ruvkun laboratory members for reading the manuscript and many discussions; the laboratories of J. Kaplan and F. Ausubel for discussions; and the Leukemia and Lymphoma Society, and EMBO for funding to S.E.J.F. NR 43 TC 47 Z9 60 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 25 PY 2008 VL 455 IS 7212 BP 491 EP U23 DI 10.1038/nature07274 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 351TU UT WOS:000259449600037 PM 18784652 ER PT J AU Firestein, R Bass, AJ Kim, SY Dunn, IF Silver, SJ Guney, I Freed, E Ligon, AH Vena, N Ogino, S Chheda, MG Tamayo, P Finn, S Shrestha, Y Boehm, JS Jain, S Bojarski, E Mermel, C Barretina, J Chan, JA Baselga, J Tabernero, J Root, DE Fuchs, CS Loda, M Shivdasani, RA Meyerson, M Hahn, WC AF Firestein, Ron Bass, Adam J. Kim, So Young Dunn, Ian F. Silver, Serena J. Guney, Isil Freed, Ellen Ligon, Azra H. Vena, Natalie Ogino, Shuji Chheda, Milan G. Tamayo, Pablo Finn, Stephen Shrestha, Yashaswi Boehm, Jesse S. Jain, Supriya Bojarski, Emeric Mermel, Craig Barretina, Jordi Chan, Jennifer A. Baselga, Jose Tabernero, Josep Root, David E. Fuchs, Charles S. Loda, Massimo Shivdasani, Ramesh A. Meyerson, Matthew Hahn, William C. TI CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity SO NATURE LA English DT Article ID GENE-EXPRESSION; C-MYC; ACTIVATION; APC; IDENTIFICATION; MUTATIONS; PATHWAY; COMPLEX; CELLS; MELANOMA AB Aberrant activation of the canonical WNT/beta-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival(1,2). Although dysregulated beta-catenin activity drives colon tumorigenesis, further genetic perturbations are required to elaborate full malignant transformation(3). To identify genes that both modulate beta-catenin activity and are essential for colon cancer cell proliferation, we conducted two loss-of-function screens in human colon cancer cells and compared genes identified in these screens with an analysis of copy number alterations in colon cancer specimens. One of these genes, CDK8, which encodes a member of the mediator complex(4), is located at 13q12.13, a region of recurrent copy number gain in a substantial fraction of colon cancers. Here we show that the suppression of CDK8 expression inhibits proliferation in colon cancer cells characterized by high levels of CDK8 and beta-catenin hyperactivity. CDK8 kinase activity was necessary for beta-catenin-driven transformation and for expression of several beta-catenin transcriptional targets. Together these observations suggest that therapeutic interventions targeting CDK8 may confer a clinical benefit in beta-catenin-driven malignancies. C1 [Firestein, Ron; Bass, Adam J.; Kim, So Young; Dunn, Ian F.; Guney, Isil; Freed, Ellen; Vena, Natalie; Ogino, Shuji; Chheda, Milan G.; Shrestha, Yashaswi; Jain, Supriya; Bojarski, Emeric; Mermel, Craig; Barretina, Jordi; Fuchs, Charles S.; Loda, Massimo; Shivdasani, Ramesh A.; Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Firestein, Ron; Ligon, Azra H.; Ogino, Shuji; Finn, Stephen; Chan, Jennifer A.; Loda, Massimo; Meyerson, Matthew] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Bass, Adam J.; Kim, So Young; Shivdasani, Ramesh A.; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Firestein, Ron; Bass, Adam J.; Kim, So Young; Dunn, Ian F.; Guney, Isil; Freed, Ellen; Ligon, Azra H.; Vena, Natalie; Ogino, Shuji; Chheda, Milan G.; Finn, Stephen; Shrestha, Yashaswi; Jain, Supriya; Bojarski, Emeric; Mermel, Craig; Barretina, Jordi; Chan, Jennifer A.; Fuchs, Charles S.; Loda, Massimo; Shivdasani, Ramesh A.; Meyerson, Matthew; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chheda, Milan G.] Massachusetts Gen Hosp, Dept Neurooncol, Boston, MA 02114 USA. [Firestein, Ron; Bass, Adam J.; Kim, So Young; Dunn, Ian F.; Guney, Isil; Shrestha, Yashaswi; Mermel, Craig; Barretina, Jordi; Root, David E.; Fuchs, Charles S.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Firestein, Ron; Bass, Adam J.; Kim, So Young; Dunn, Ian F.; Silver, Serena J.; Guney, Isil; Chheda, Milan G.; Tamayo, Pablo; Shrestha, Yashaswi; Boehm, Jesse S.; Mermel, Craig; Barretina, Jordi; Chan, Jennifer A.; Root, David E.; Meyerson, Matthew; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Baselga, Jose; Tabernero, Josep] Hosp Gen Valle Hebron, Dept Med Oncol, Barcelona 08035, Spain. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU US NCI/NIH [R33CA128625]; NIH [T32]; GI SPORE Career Development [P50CA127003]; Harvard-MIT Clinical Investigator Training Program Fellowship; Department of Defense Prostate Cancer Postdoctoral Fellowships; Warren-Whitman- Richardson, Hagerty Foundation Research Fellowships; K12 award FX We thank E. Shin for technical assistance with immunohistochemistry, M. Miri for assistance with sample collection and G. Getz for assistance with SNP array analysis. This work was supported in part by a grant from the US NCI/NIH R33CA128625 (W.C.H.), T32 NIH grant (R.F.) and a GI SPORE Career Development Grant (P50CA127003; R.F.), a Harvard-MIT Clinical Investigator Training Program Fellowship (A.J.B), Department of Defense Prostate Cancer Postdoctoral Fellowships (I.G. and S.Y.K.), Warren-Whitman- Richardson, Hagerty Foundation Research Fellowships (I.F.D.) and K12 award (M.G.C.). J.B. is a Beatriu de Pinos Fellow of the Departament d'Educacio i Universitats de la Generalita de Catalunya. NR 30 TC 289 Z9 299 U1 6 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 25 PY 2008 VL 455 IS 7212 BP 547 EP U60 DI 10.1038/nature07179 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 351TU UT WOS:000259449600049 PM 18794900 ER PT J AU Morris, EJ Ji, JY Yang, FJ Di Stefano, L Herr, A Moon, NS Kwon, EJ Haigis, KM Naar, AM Dyson, NJ AF Morris, Erick J. Ji, Jun-Yuan Yang, Fajun Di Stefano, Luisa Herr, Anabel Moon, Nam-Sung Kwon, Eun-Jeong Haigis, Kevin M. Naar, Anders M. Dyson, Nicholas J. TI E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8 SO NATURE LA English DT Article ID COLON-CANCER; EXPRESSION; ACTIVATION; PROTEIN; GENE; APC; P53; SPECIFICITY; DROSOPHILA; MEDIATOR AB The E2F1 transcription factor can promote proliferation or apoptosis when activated, and is a key downstream target of the retinoblastoma tumour suppressor protein ( pRB). Here we show that E2F1 is a potent and specific inhibitor of beta-catenin/T-cell factor (TCF)- dependent transcription, and that this function contributes to E2F1- induced apoptosis. E2F1 deregulation suppresses beta-catenin activity in an adenomatous polyposis coli ( APC)/glycogen synthase kinase- 3 ( GSK3)- independent manner, reducing the expression of key beta-catenin targets including c- MYC. This interaction explains why colorectal tumours, which depend on beta- catenin transcription for their abnormal proliferation, keep RB1 intact. Remarkably, E2F1 activity is also repressed by cyclin- dependent kinase- 8 ( CDK8), a colorectal oncoprotein(1). Elevated levels of CDK8 protect beta-catenin/TCF-dependent transcription from inhibition by E2F1. Thus, by retaining RB1 and amplifying CDK8, colorectal tumour cells select conditions that collectively suppress E2F1 and enhance the activity of beta-catenin. C1 [Morris, Erick J.; Ji, Jun-Yuan; Yang, Fajun; Di Stefano, Luisa; Herr, Anabel; Moon, Nam-Sung; Haigis, Kevin M.; Naar, Anders M.; Dyson, Nicholas J.] Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA 02129 USA. [Morris, Erick J.; Ji, Jun-Yuan; Yang, Fajun; Di Stefano, Luisa; Herr, Anabel; Moon, Nam-Sung; Haigis, Kevin M.; Naar, Anders M.; Dyson, Nicholas J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Yang, Fajun; Naar, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Kwon, Eun-Jeong] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kwon, Eun-Jeong] Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc, Lab Mol Pathol, Charlestown, MA 02129 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM dyson@helix.mgh.harvard.edu FU Ruth L. Kirschstein Award; Tosteson Postdoctoral Fellowship; MGH ECOR Fund for Medical Discovery; Career Development award; Harvard Gastrointestinal Specialized Program of Research Excellence [P50-CA127003]; Saltonstall Foundation; National Institutes of Health [GM81607, GM053203, GM071449] FX We thank many investigators for their gifts of cell lines, plasmids and fly stocks, especially S. Artavanis-Tsakonas. We thank D. Rennie and the Massachusetts General Hospital Cutaneous Biology Research Center Transgenic Fly Core for embryo injections, and B. Fowle for his help with SEM imaging. We thank A. McClatchey, J. Settleman, C. Seum and T. Orr-Weaver for their gifts of antibodies. We thank our colleagues at the Massachusetts General Hospital (MGH) Cancer Center for discussions. E.J.M. and J.-Y.J. are supported in part by a Ruth L. Kirschstein Award and a Tosteson Postdoctoral Fellowship, respectively. L. D. S. is supported by the MGH ECOR Fund for Medical Discovery. N.-S.M. is a Leukemia and Lymphoma Society Special Fellow. K.M.H. was supported by a Career Development award from the Harvard Gastrointestinal Specialized Program of Research Excellence (GI-SPORE) (P50-CA127003). N.J.D. was supported by a scholarship from the Saltonstall Foundation. This study was supported by grants from the National Institutes of Health to N.J.D. (GM81607, GM053203) and A. M. N. (GM071449). NR 29 TC 160 Z9 161 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 25 PY 2008 VL 455 IS 7212 BP 552 EP U67 DI 10.1038/nature07310 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 351TU UT WOS:000259449600050 PM 18794899 ER PT J AU Gradishar, WJ Bellon, JR Gadd, MA D'Alessandro, HA Braaten, K Smith, BL Harris, NL AF Gradishar, William J. Bellon, Jennifer R. Gadd, Michele A. D'Alessandro, Helen Anne Braaten, Kristina Smith, Barbara L. Harris, Nancy Lee TI A woman with a mass in the breast and a solitary lesion in the spine - Breast cancer with minimal metastatic disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Conference on Breast Cancer - Current Controversies and New Horizons CY JUL 12, 2007 CL Boston, MA ID ADJUVANT ENDOCRINE THERAPY; ESTROGEN-RECEPTOR STATUS; LONG-TERM SURVIVAL; PROGNOSTIC-FACTORS; PREMENOPAUSAL PATIENTS; RANDOMIZED-TRIAL; PRIMARY TUMOR; COMBINATION CHEMOTHERAPY; SURGICAL RESECTION; HEPATIC RESECTION C1 [Gradishar, William J.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Gradishar, William J.] Feinberg Sch Med, Chicago, IL USA. [Bellon, Jennifer R.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Bellon, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gadd, Michele A.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. [D'Alessandro, Helen Anne] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Braaten, Kristina] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bellon, Jennifer R.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Gadd, Michele A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [D'Alessandro, Helen Anne] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Braaten, Kristina] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gradishar, WJ (reprint author), Northwestern Univ, Dept Med, Chicago, IL 60611 USA. NR 47 TC 3 Z9 3 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 SEP 25 PY 2008 VL 359 IS 13 BP 1382 EP 1391 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 351QZ UT WOS:000259440900010 PM 18815400 ER PT J AU Chinnaiyan, P Wang, M Rojiani, AM Tofilon, PJ Chakravarti, A Ang, KK Zhang, HZ Hammond, E Curran, W Mehta, MP AF Chinnaiyan, Prakash Wang, Meihua Rojiani, Amyn M. Tofilon, Philip J. Chakravarti, Arnab Ang, K. Kian Zhang, Hua-Zhong Hammond, Elizabeth Curran, Walter, Jr. Mehta, Minesh P. TI The prognostic value of nestin expression in newly diagnosed glioblastoma: Report from the Radiation Therapy Oncology Group SO RADIATION ONCOLOGY LA English DT Article ID STEM-CELL MARKERS; INTERMEDIATE FILAMENT PROTEIN; HUMAN ASTROCYTOMAS; PROGENITOR CELLS; DIFFERENT TUMORS; NERVOUS-SYSTEM; PHOSPHORYLATION; IDENTIFICATION; MALIGNANCY; GLIOMA AB Background: Nestin is an intermediate filament protein that has been implicated in early stages of neuronal lineage commitment. Based on the heterogeneous expression of nestin in GBM and its potential to serve as a marker for a dedifferentiated, and perhaps more aggressive phenotype, the Radiation Therapy Oncology Group (RTOG) sought to determine the prognostic value of nestin expression in newly diagnosed GBM patients treated on prior prospective RTOG clinical trials. Methods: Tissue microarrays were prepared from 156 patients enrolled in these trials. These specimens were stained using a mouse monoclonal antibody specific for nestin and expression was measured by computerized quantitative image analysis using the Ariol SL-50 system. The parameters measured included both staining intensity and the relative area of expression within a specimen. This resulted into 3 categories: low, intermediate, and high nestin expression, which was then correlated with clinical outcome. Results: A total of 153 of the 156 samples were evaluable for this study. There were no statistically significant differences between pretreatment patient characteristics and nestin expression. There was no statistically significant difference in either overall survival or progression-free survival (PFS) demonstrated, although a trend in decreased PFS was observed with high nestin expression (p = 0.06). Conclusion: Although the correlation of nestin expression and histologic grade in glioma is of considerable interest, the presented data does not support its prognostic value in newly diagnosed GBM. Further studies evaluating nestin expression may be more informative when studied in lower grade glioma, in the context of markers more specific to tumor stem cells, and using more recent specimens from patients treated with temozolomide in conjunction with radiation. C1 [Chinnaiyan, Prakash] H Lee Moffitt Canc Ctr & Res Inst, Dept Radiat Oncol, Tampa, FL USA. [Wang, Meihua] Amer Coll Radiol, Dept Stat, Philadelphia, PA USA. [Rojiani, Amyn M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Pathol, Tampa, FL USA. [Tofilon, Philip J.] H Lee Moffitt Canc Ctr & Res Inst, Dept Drug Discovery, Tampa, FL USA. [Chakravarti, Arnab] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Ang, K. Kian; Zhang, Hua-Zhong] Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Hammond, Elizabeth] LDS Hosp, Dept Pathol, Salt Lake City, UT USA. [Curran, Walter, Jr.] Emory Univ, Dept Radiat Oncol, Atlanta, GA 30322 USA. [Mehta, Minesh P.] Univ Wisconsin Hosp, Dept Human Oncol, Madison, WI USA. RP Chinnaiyan, P (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Radiat Oncol, Tampa, FL USA. EM prakash.chinnaiyan@moffitt.org; mwang@phila.acr.org; Amyn.Rojiani@moffitt.org; Philip.Tofilon@moffitt.org; ACHAKRAVARTI@PARTNERS.ORG; kianang@mdanderson.org; huazhang@mdanderson.org; Elizabeth.Hammond@imail.org; curran@radonc.emory.org; mehta@humonc.wisc.edu OI mehta, minesh/0000-0002-4812-5713 FU American Cancer Society's Institutional Research [93-032-13]; Analytic Microscopy Core Facility FX This project was supported (in part) by the American Cancer Society's Institutional Research Grant #93-032-13 (P. C.) and the Analytic Microscopy Core Facility at the H. Lee Moffitt Cancer Center. We would also like to thank Noel Clark for his assistance with immunohistochemical staining. NR 27 TC 29 Z9 31 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-717X J9 RADIAT ONCOL JI Radiat. Oncol. PD SEP 25 PY 2008 VL 3 AR 32 DI 10.1186/1748-717X-3-32 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 365PC UT WOS:000260418300001 PM 18817556 ER PT J AU Lieberman, DA Holub, JL Moravec, MD Eisen, GM Peters, D Morris, CD AF Lieberman, David A. Holub, Jennifer L. Moravec, Matthew D. Eisen, Glenn M. Peters, Dawn Morris, Cynthia D. TI Prevalence of colon polyps detected by colonoscopy screening in asymptomatic black and white patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COLORECTAL-CANCER; AFRICAN-AMERICANS; ANATOMICAL DISTRIBUTION; MEDICARE POPULATION; ADENOMATOUS POLYPS; UNITED-STATES; SURVEILLANCE; LOCATION; PATTERNS; GENDER AB Context Compared with white individuals, black men and women have a higher incidence and mortality from colorectal cancer and may develop cancer at a younger age. Colorectal cancer screening might be less effective in black individuals, if there are racial differences in the age- adjusted prevalence and location of cancer precursor lesions. Objectives To determine and compare the prevalence rates and location of polyps sized more than 9 mm in diameter in asymptomatic black and white individuals who received colonoscopy screening. Design, Setting, and Patients Colonoscopy data were prospectively collected from 67 adult gastrointestinal practice sites in the United States using a computerized endoscopic report generator between January 1, 2004, and December 31, 2005. Data were transmitted to a central data repository, where all asymptomatic white ( n = 80 061) and black ( n= 5464) patients who had received screening colonoscopy were identified. Main Outcome Measures Prevalence and location of polyps sized more than 9 mm, adjusted for age, sex, and family history of colorectal cancer in a multivariate analysis. Results Both black men and women had a higher prevalence of polyps sized more than 9 mm in diameter compared with white men and women ( 422 [ 7.7%] vs 4964 [ 6.2%]; P <. 001). Compared with white patients, the adjusted odds ratio ( OR) for black men was 1.16 ( 95% confidence interval [ CI], 1.01- 1.34) and the adjusted OR for black women was 1.62 ( 95% CI, 1.39- 1.89). Black and white patients had a similar risk of proximal polyps sized more than 9 mm( OR, 1.13; 95% CI, 0.93- 1.38). However, in a subanalysis of patients older than 60 years, proximal polyps sized more than 9 mm were more likely prevalent in black men ( P=. 03) and women ( P <. 001) compared with white men and women. Conclusion Compared with white individuals, black men and women undergoing screening colonoscopy have a higher risk of polyps sized more than 9 mm, and black individuals older than 60 years are more likely to have proximal polyps sized more than 9 mm. C1 [Lieberman, David A.] Portland VA Med Ctr, Div Gastroenterol, Portland, OR 97239 USA. [Lieberman, David A.; Holub, Jennifer L.; Moravec, Matthew D.; Eisen, Glenn M.] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. [Peters, Dawn] Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Morris, Cynthia D.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Lieberman, DA (reprint author), Portland VA Med Ctr, Div Gastroenterol, 1037 SW Vet Hosp Rd,P3-GI, Portland, OR 97239 USA. EM lieberma@ohsu.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [UO1 DK57132, R33-DK61778-01]; AstraZeneca FX This work was supported by grants UO1 DK57132 and R33-DK61778-01 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) since 1999, and funding from AstraZeneca. NR 24 TC 112 Z9 114 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 24 PY 2008 VL 300 IS 12 BP 1417 EP 1422 DI 10.1001/jama.300.12.1417 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 351FR UT WOS:000259410400019 PM 18812532 ER PT J AU Rehm, KJ Deeg, KE Marder, E AF Rehm, Kristina J. Deeg, Katherine E. Marder, Eve TI Developmental regulation of neuromodulator function in the stomatogastric ganglion of the lobster, Homarus americanus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE central pattern generator; CabTRP1a; Val(1)-SIFamide; RPCH; crustacean; maturation ID RAT SPINAL-CORD; CENTRAL PATTERN GENERATOR; SINGLE EMBRYONIC NETWORK; NERVOUS-SYSTEM; SUBSTANCE-P; MOTOR PATTERNS; NEUROKININ-1 RECEPTOR; PHYSIOLOGICAL ACTIONS; BURSTING ACTIVITY; NEURAL CIRCUITS AB Neuromodulatory substances have profound effects on the two motor patterns generated by the adult crustacean stomatogastric ganglion (STG), the gastric mill rhythm and the pyloric rhythm. Developmentally regulated changes in the modulatory functions of neuromodulators could therefore play an important role in the maturation of the output from the developing STG. We compared the effects of neuromodulators on isolated embryonic and adult STG of the lobster, Homarus americanus. Bath application of Val(1)-SIFamide, a peptide whose expression is different in embryos and adults, activated different neuron classes in embryos and adults. Cancer borealis tachykinin-related peptide 1a, a peptide that does not appear in the terminals of modulatory neurons in the STG until after embryonic development, also produced different motor patterns in embryos and adults. In contrast, red pigment concentrating hormone, a peptide with a similar distribution in the STNS across development, produced similar motor patterns in embryonic and adult STG. Proctolin, serotonin, and allatostatin were also physiologically active on the isolated embryonic STG. Together, these results demonstrate that receptors to many neuromodulators are present and functional on STG neurons before the motor patterns of the stomatogastric nervous system are mature. Moreover, neuromodulator responses change during development, perhaps contributing to the maturation of the output from the stomatogastric nervous system. C1 [Rehm, Kristina J.; Deeg, Katherine E.; Marder, Eve] Brandeis Univ, Volen Ctr, Waltham, MA 02454 USA. RP Rehm, KJ (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 620, Boston, MA 02115 USA. EM Kristina_Rehm@DFCI.Harvard.edu RI Marder, Eve/A-5713-2012 FU National Institutes of Health [NS050479, NS017813] FX This work was supported by National Institutes of Health Grants NS050479 (K.J.R.) and NS017813 (E. M.). We thank Dr. Adam L. Taylor at Brandeis University (Waltham, MA) for designing the spectral analysis methods, Dr. Michael P. Nusbaum at the University of Pennsylvania (Philadelphia, PA) for the CabTRP peptide, Dr. Patsy S. Dickinson at Bowdoin College ( Brunswick, ME) for the Val1-SIFamide peptide, and Dr. Andrew E. Christie at the University of Hawaii (Honolulu, HI) for the Val1-SIFamide antibody. NR 60 TC 14 Z9 14 U1 1 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 SEP 24 PY 2008 VL 28 IS 39 BP 9828 EP 9839 DI 10.1523/JNEUROSCI.2328-08.2008 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 352MG UT WOS:000259500700022 PM 18815267 ER PT J AU Chen, G Kozell, LB Hitzemann, R Buck, KJ AF Chen, Gang Kozell, Laura B. Hitzemann, Robert Buck, Kari J. TI Involvement of the limbic basal ganglia in ethanol withdrawal convulsivity in mice is influenced by a chromosome 4 locus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE seizure; c-Fos; substantia nigra; lesion; Mpdz; MUPP1 ID NIGRA PARS RETICULATA; RAT SUBSTANTIA-NIGRA; C-FOS EXPRESSION; ACUTE ALCOHOL-WITHDRAWAL; GAMMA-AMINOBUTYRIC-ACID; SUBTHALAMIC NUCLEUS; VENTRAL PALLIDUM; GLOBUS-PALLIDUS; DEVELOPMENTAL REGULATION; INFERIOR COLLICULUS AB Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains ethanol (alcohol) use/abuse and may contribute to relapse in alcoholics. Although no animal model duplicates alcoholism, models for specific factors, like the withdrawal syndrome, are useful for identifying potential genetic and neural determinants of liability in humans. We generated congenic mice that confirm a quantitative trait locus (QTL) on chromosome 4 with a large effect on predisposition to alcohol withdrawal. Using c-Fos expression as a high-resolution marker of neuronal activation, congenic mice demonstrated significantly less neuronal activity associated with ethanol withdrawal than background strain mice in the substantia nigra pars reticulata (SNr), subthalamic nucleus (STN), rostromedial lateral globus pallidus, and ventral pallidum. Notably, neuronal activation in subregions of the basal ganglia associated with limbic function was more intense than in subregions associated with sensorimotor function. Bilateral lesions of caudolateral SNr attenuated withdrawal severity after acute and repeated ethanol exposures, whereas rostrolateral SNr and STN lesions did not reduce ethanol withdrawal severity. Caudolateral SNr lesions did not affect pentylenetetrazol-enhanced convulsions. Our results suggest that this QTL impacts ethanol withdrawal via basal ganglia circuitry associated with limbic function and that the caudolateral SNr plays a critical role. These are the first analyses to elucidate circuitry by which a confirmed addiction-relevant QTL influences behavior. This mouse QTL is syntenic with human chromosome 9p. Given the growing body of evidence that a gene(s) on chromosome 9p influences alcoholism, our results can facilitate human research on alcohol dependence and withdrawal. C1 [Chen, Gang] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Res Serv R&D40, Dept Behav Neurosci, Portland, OR 97239 USA. [Kozell, Laura B.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Chen, Gang; Kozell, Laura B.; Hitzemann, Robert; Buck, Kari J.] Portland Alcohol Res Ctr, Portland, OR 97239 USA. [Hitzemann, Robert; Buck, Kari J.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Chen, G (reprint author), Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Res Serv R&D40, Dept Behav Neurosci, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM chenga@ohsu.edu OI Kozell, Laura/0000-0003-3059-2046 FU Public Health Service [AA011114, AA10760, DA05228, AA11034, AA13484]; Veterans Affairs FX This work was supported by Public Health Service Grants AA011114, AA10760, DA05228, AA11034, and AA13484 and a Veterans Affairs Merit grant. We are grateful to Drs. Charles Meshul, John Belknap, John Crabbe, and Pam Metten for many helpful discussions of these experiments and their comments on a draft of this manuscript. NR 78 TC 13 Z9 13 U1 2 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 SEP 24 PY 2008 VL 28 IS 39 BP 9840 EP 9849 DI 10.1523/JNEUROSCI.1713-08.2008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 352MG UT WOS:000259500700023 PM 18815268 ER PT J AU Young, G Albisetti, M Bonduel, M Brandao, L Chan, A Friedrichs, F Goldenberg, NA Grabowski, E Heller, C Journeycake, J Kenet, G Krumpel, A Kurnik, K Lubetsky, A Male, C Manco-Johnson, M Mathew, P Monagle, P van Ommen, H Simioni, P Svirin, P Tormene, D Nowak-Gottl, U AF Young, Guy Albisetti, Manuela Bonduel, Mariana Brandao, Leonardo Chan, Anthony Friedrichs, Frauke Goldenberg, Neil A. Grabowski, Eric Heller, Christine Journeycake, Janna Kenet, Gili Kruempel, Anne Kurnik, Karin Lubetsky, Aaron Male, Christoph Manco-Johnson, Marilyn Mathew, Prasad Monagle, Paul van Ommen, Heleen Simioni, Paolo Svirin, Pavel Tormene, Daniela Nowak-Goettl, Ulrike TI Impact of inherited thrombophilia on venous thromboembolism in children - A systematic review and meta-analysis of observational studies SO CIRCULATION LA English DT Review DE meta-analysis; pediatrics; recurrence; thrombosis ID FACTOR-V-LEIDEN; PROTHROMBOTIC RISK-FACTORS; ACTIVATED PROTEIN-C; ARTERIAL ISCHEMIC-STROKE; PORTAL-VEIN THROMBOSIS; CEREBRAL SINOVENOUS THROMBOSIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE G20210A MUTATION; G-A MUTATION; SINGLE-CENTER AB Background - The aim of the present study was to estimate the impact of inherited thrombophilia (IT) on the risk of venous thromboembolism (VTE) onset and recurrence in children by a meta-analysis of published observational studies. Methods and Results - A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2007 was conducted using key words in combination as both MeSH terms and text words. Citations were independently screened by 2 authors, and those meeting the inclusion criteria defined a priori were retained. Data on year of publication, study design, country of origin, number of patients/controls, ethnicity, VTE type, and frequency of recurrence were abstracted. Heterogeneity across studies was evaluated, and summary odds ratios and 95% CIs were calculated with both fixed-effects and random-effects models. Thirty-five of 50 studies met inclusion criteria. No significant heterogeneity was discerned across studies. Although > 70% of patients had at least 1 clinical risk factor for VTE, a statistically significant association with VTE onset was demonstrated for each IT trait evaluated (and for combined IT traits), with summary odds ratios ranging from 2.63 (95% CI, 1.61 to 4.29) for the factor II variant to 9.44 (95% CI, 3.34 to 26.66) for antithrombin deficiency. Furthermore, a significant association with recurrent VTE was found for all IT traits except the factor V variant and elevated lipoprotein(a). Conclusions - The present meta-analysis indicates that detection of IT is clinically meaningful in children with, or at risk for, VTE and underscores the importance of pediatric thrombophilia screening programs. C1 [Young, Guy] Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. [Albisetti, Manuela] Univ Childrens Hosp, Div Hematol, Zurich, Switzerland. [Bonduel, Mariana] Hosp Pediat Prof Dr JP Garrahan, Serv Hematol & Oncol, Buenos Aires, DF, Argentina. [Brandao, Leonardo] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Chan, Anthony] McMaster Univ, Hamilton, ON, Canada. [Friedrichs, Frauke] Univ Munster, Leibniz Inst Arteriosclerosis Res, Munster, Germany. [Goldenberg, Neil A.; Manco-Johnson, Marilyn] Univ Colorado, Dept Pediat, Denver, CO 80202 USA. [Goldenberg, Neil A.; Manco-Johnson, Marilyn] Childrens Hosp, Denver, CO 80218 USA. [Grabowski, Eric] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Heller, Christine] Univ Hosp Frankfurt, Dept Pediat Hematol Oncol, Frankfurt, Germany. [Journeycake, Janna] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Kenet, Gili; Lubetsky, Aaron] Chaim Sheba Med Ctr, Israel Natl Haemophilia Ctr, IL-52621 Tel Hashomer, Israel. [Kruempel, Anne; Nowak-Goettl, Ulrike] Univ Hosp Munster, Dept Pediat Hematol Oncol, D-48149 Munster, Germany. [Kurnik, Karin] Univ Hosp Munich, Dept Pediat, Munich, Germany. [Male, Christoph] Med Univ, Dept Pediat, Vienna, Austria. [Mathew, Prasad] Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA. [Monagle, Paul] Royal Childrens Hosp, Melbourne, Vic, Australia. [van Ommen, Heleen] Emma Childrens Hosp AMC, Dept Pediat Hematol, Amsterdam, Netherlands. [Simioni, Paolo; Tormene, Daniela] Univ Padua, Dept Med & Surg Sci, Padua, Italy. [Svirin, Pavel] Moscow State Med Univ, Russian Natl Ctr Pediat Hematol Oncol, Moscow, Russia. RP Nowak-Gottl, U (reprint author), Univ Hosp Munster, Dept Pediat Hematol Oncol, Albert Schweitzer Str 33, D-48149 Munster, Germany. RI Young, Guy/I-1880-2012; OI Young, Guy/0000-0001-6013-1254; SIMIONI, PAOLO/0000-0002-6744-383X; Chan, Anthony K. C./0000-0003-1551-3995 FU Karl Brocker Stiftung; Innovative Medizinische Forschung in Munster FX The study was supported by grants from the Karl Brocker Stiftung and the local university research project Innovative Medizinische Forschung in Munster. These study supporters had no role in the study design, data collection, data analysis, or data interpretation or in the writing of this report. NR 125 TC 94 Z9 102 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 23 PY 2008 VL 118 IS 13 BP 1373 EP 1382 DI 10.1161/CIRCULATIONAHA.108.789008 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 351CO UT WOS:000259402300010 PM 18779442 ER PT J AU Bhatt, DL AF Bhatt, Deepak L. TI What makes platelets angry - Diabetes, fibrinogen, obesity, and impaired response to antiplatelet therapy? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE diabetes; platelets ID PERCUTANEOUS CORONARY INTERVENTION; ARTERY-DISEASE; CLOPIDOGREL; MELLITUS; ASPIRIN; INHIBITION; REACTIVITY; RESISTANCE C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 75 Francis St, Boston, MA 02115 USA. EM DLBHATTMD@ALUM.MIT.EDU NR 20 TC 24 Z9 25 U1 0 U2 1 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 SEP 23 PY 2008 VL 52 IS 13 BP 1060 EP 1061 DI 10.1016/j.jacc.2008.06.027 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 349OR UT WOS:000259290700004 PM 18848138 ER PT J AU Giugliano, RP Braunwald, E AF Giugliano, Robert P. Braunwald, Eugene TI The year in non-ST-segment elevation acute coronary syndrome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE non-ST-segment; coronary; syndrome ID ACUTE MYOCARDIAL-INFARCTION; GLOMERULAR-FILTRATION-RATE; UNSTABLE ANGINA-PECTORIS; CONGESTIVE-HEART-FAILURE; UNFRACTIONATED HEPARIN; GLOBAL REGISTRY; CARDIOVASCULAR EVENTS; ANTIPLATELET THERAPY; POSTMYOCARDIAL INFARCTION; RISK STRATIFICATION C1 [Giugliano, Robert P.; Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Div Cardiovasc Med,TIMI Study Grp, Boston, MA USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 79 TC 5 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 23 PY 2008 VL 52 IS 13 BP 1095 EP 1103 DI 10.1016/j.jacc.2008.07.005 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 349OR UT WOS:000259290700010 PM 18848144 ER PT J AU Peleg, AY Tampakakis, E Fuchs, BB Eliopoulos, GM Moellering, RC Mylonakis, E AF Peleg, Anton Y. Tampakakis, Emmanouil Fuchs, Beth Burgwyn Eliopoulos, George M. Moellering, Robert C., Jr. Mylonakis, Eleftherios TI Prokaryote-eukaryote interactions identified by using Caenorhabditis elegans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE A. baumannii; C. albicans; Acinetobacter; pathogenesis; biofilm ID QUORUM-SENSING MOLECULE; INTENSIVE-CARE UNITS; CANDIDA-ALBICANS; ACINETOBACTER-BAUMANNII; NOSOCOMIAL INFECTIONS; VIRULENCE FACTORS; BIOFILM FORMATION; MUTANTS; MORPHOLOGY; REPRESSOR AB Prokaryote-eukaryote interactions are ubiquitous and have important medical and environmental significance. Despite this, a paucity of data exists on the mechanisms and pathogenic consequences of bacterial-fungal encounters within a living host. We used the nematode Caenorhabditis elegans as a substitute host to study the interactions between two ecologically related and clinically troublesome pathogens, the prokaryote, Acinetobacter baumannii, and the eukaryote, Candida albicans. After co-infecting C. elegans with these organisms, we observed that A. baumannii inhibits filamentation, a key virulence determinant of C. albicans. This antagonistic, cross-kingdom interaction led to attenuated virulence of C. albicans, as determined by improved nematode survival when infected with both pathogens. In vitro coinfection assays in planktonic and biofilm environments supported the inhibitory effects of A. balumannii toward C. albicans, further showing a predilection of A. baumannii for C. albicans filaments. Interestingly, we demonstrate a likely evolutionary defense by C. albicans against A. baumannii, whereby C. albicans inhibits A. baumannii growth once a quorum develops. This counteroffensive is at least partly mediated by the C. albicans quorum-sensing molecule farnesol. We used the C. elegans-A.aumannii-C. albicans coinfection model to screen an A. baumannii mutant library, leading to the identification of several mutants attenuated in their inhibitory activity toward C. albicans. These findings present an extension to the current paradigm of studying monomicrobial pathogenesis in C. elegans and by use of genetic manipulation, provides a whole-animal model system to investigate the complex dynamics of a polymicrobial infection. C1 [Peleg, Anton Y.; Tampakakis, Emmanouil; Fuchs, Beth Burgwyn; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Peleg, Anton Y.; Eliopoulos, George M.; Moellering, Robert C., Jr.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02115 USA. [Peleg, Anton Y.; Fuchs, Beth Burgwyn; Eliopoulos, George M.; Moellering, Robert C., Jr.; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org OI Peleg, Anton/0000-0002-2296-2126 FU National Institutes of Health K08 Award [AI63084]; R01 Award [AI075286]; Ellison Medical Foundation; University of Queensland Postgraduate Scholarship Award FX We thank Tara Thurber and team from the Massachusetts General Hospital Genetics CORE laboratory for use of the Hudson Rapid-Pick robot and Gerald Fink for the C. albicans nrg1 mutant. Support was provided by National Institutes of Health K08 Award AI63084 and R01 Award AI075286 (to E.M.), a New Scholar Award in Global Infectious Diseases from the Ellison Medical Foundation (to E.M.), and a University of Queensland Postgraduate Scholarship Award (to A.Y.P.). NR 34 TC 85 Z9 92 U1 1 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 23 PY 2008 VL 105 IS 38 BP 14585 EP 14590 DI 10.1073/pnas.0805048105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 353TY UT WOS:000259592400065 PM 18794525 ER PT J AU d'Avila, A Ruskin, JN AF d'Avila, Andre Ruskin, Jeremy N. TI Nonpharmacologic strategies: The evolving story of ablation and hybrid therapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT CME Satellite Symposium on Demystifying the Rate vs Rhythm Conundrum - New Perspectives in Recent Trials and Future Treatment Options CY MAY 10, 2007 CL Denver, CO ID PULMONARY-VEIN ABLATION; PAROXYSMAL ATRIAL-FIBRILLATION; CATHETER ABLATION; RADIOFREQUENCY ABLATION; RANDOMIZED-TRIAL; ANTRUM ISOLATION; EFFICACY; EXPERIENCE; OUTCOMES; SAFETY AB Technologic advancements have resulted in the more widespread use of catheter ablation to restore sinus rhythm in patients with atrial fibrillation (AF) and elicit improvement in symptoms, quality of life, and prognosis. However, the effectiveness of this procedure to prevent the occurrence of heart failure and stroke while reducing mortality has yet to be proved in major clinical trials. Factors influencing the results of ablation and possibly obfuscating the interpretation of data from early studies include variations in center experience and operator skill, the definition of procedural success, and follow-up interval and duration, as well as the complexity and heterogeneity of AF itself. Upcoming trials that will examine outcomes after catheter ablation and pharmacologic strategies from the end points of heart failure, stroke, and mortality are anticipated to yield more definitive conclusions about ablation efficacy. (C) 2008 Elsevier Inc. All rights reserved. C1 [d'Avila, Andre; Ruskin, Jeremy N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP d'Avila, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St GRB 109, Boston, MA 02114 USA. EM adavila@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 24 TC 8 Z9 8 U1 0 U2 3 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 SEP 22 PY 2008 VL 102 IS 6A SU S BP 20H EP 24H DI 10.1016/j.amjcard.2008.06.026 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 355DL UT WOS:000259689100004 PM 18790111 ER PT J AU Garg, HG Mrabat, H Yu, LY Freeman, C Li, BYZ Zhang, FM Linhardt, RJ Hales, CA AF Garg, Hari G. Mrabat, Hicham Yu, Lunyin Freeman, Craig Li, Boyangzi Zhang, Fuming Linhardt, Robert J. Hales, Charles A. TI Significance of the 2-O-sulfo group of L-iduronic acid residues in heparin on the growth inhibition of bovine pulmonary artery smooth muscle cells SO CARBOHYDRATE RESEARCH LA English DT Article DE heparin; desulfated heparin; cell proliferation ID MOLECULAR-WEIGHT; ANTIPROLIFERATIVE ACTIVITY; CELLULAR PROLIFERATION; SULFATE; KINETICS; HYPOXIA; INJURY; RATS AB Heparin inhibits the growth of several cell types in vitro, including bovine pulmonary artery smooth muscle cells (BPASMCs). To understand more about the heparin structure required for endogenous activity, chemically modified derivatives of native heparin and glycol-split heparin, namely, 2-O-desulfonated iduronic/glucuronic acid residues in heparin, and 2-O-desulfonated iduronic residues in glycol-split heparin were prepared. These were assayed for their anti proliferative potency on cultured BPASMCs. All of the 2-O-desulfonated heparin derivatives had significantly decreased less antiproliferative activity on BPASMCs. These results suggest that the 2-O-sulfo group of iduronic acid residues in heparin's major sequence is essential for the antiproliferative properties of heparin. The size of heparin does not affect the growth-inhibitory properties of heparin on BPASMCs at the three dose levels examined. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Garg, Hari G.; Mrabat, Hicham; Yu, Lunyin; Hales, Charles A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. [Freeman, Craig] Australian Natl Univ, John Curtin Sch Med Res, Div Immunol & Genet, Canberra, ACT 2601, Australia. [Li, Boyangzi; Zhang, Fuming; Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Chem & Chem Biol, Biotechnol Ctr 4005, Troy, NY 12180 USA. [Li, Boyangzi; Zhang, Fuming; Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Biol, Biotechnol Ctr 4005, Troy, NY 12180 USA. [Li, Boyangzi; Zhang, Fuming; Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Chem & Biol Engn, Biotechnol Ctr 4005, Troy, NY 12180 USA. RP Garg, HG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. EM hgarg@partners.org RI Li, Boyangzi/B-4813-2012 FU National Institute of Health [HL 039150, HL 62244, GM 38060] FX This work was supported by National Institute of Health Grant HL 039150 to C.A.H. and HL 62244 and GM 38060 to RJ.L. NR 26 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 22 PY 2008 VL 343 IS 14 BP 2406 EP 2410 DI 10.1016/j.carres.2008.06.022 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 356SF UT WOS:000259797200008 PM 18656855 ER PT J AU Houser, CR Huang, CS Peng, Z AF Houser, C. R. Huang, C. S. Peng, Z. TI Dynamic seizure-related changes in extracellular signal-regulated kinase activation in a mouse model of temporal lobe epilepsy SO NEUROSCIENCE LA English DT Article DE dentate gyrus; ERK; hippocampus; immunohistochemistry; pilocarpine; spontaneous seizures ID LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; PROTEIN-KINASE; MAP-KINASE; RAT-BRAIN; SYNAPTIC PLASTICITY; STATUS EPILEPTICUS; NMDA RECEPTOR; MESSENGER-RNA; DENTATE GYRUS AB Extracellular signal-regulated kinase (ERK) is highly sensitive to regulation by neuronal activity and is critically involved in several forms of synaptic plasticity. These features suggested that alterations in ERK signaling might occur in epilepsy. Previous studies have described increased ERK phosphorylation immediately after the induction of severe seizures, but patterns of ERK activation in epileptic animals during the chronic period have not been determined. Thus, the localization and abundance of phosphorylated extracellular signal-regulated kinase (pERK) were examined in a pilocarpine model of recurrent seizures in C57BL/6 mice during the seizure-free period and at short intervals after spontaneous seizures. Immunolabeling of pERK in control animals revealed an abundance of distinctly-labeled neurons within the hippocampal formation. However, in pilocarpine-treated mice during the seizure-free period, the numbers of pERK-labeled neurons were substantially decreased throughout much of the hippocampal formation. Double labeling with a general neuronal marker suggested that the decrease in pERK-labeled neurons was not due primarily to cell loss. The decreased ERK phosphorylation in seizure-prone animals was interpreted as a compensatory response to increased neuronal excitability within the network. Nevertheless, striking increases in pERK labeling occurred at the time of spontaneous seizures and were evident in large populations of neurons at very short intervals (as early as 2 min) after detection of a behavioral seizure. These findings suggest that increased pERK labeling could be one of the earliest immunohistochemical indicators of neurons that are activated at the time of a spontaneous seizure. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Houser, C. R.; Huang, C. S.; Peng, Z.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Houser, C. R.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Houser, C. R.; Huang, C. S.] Vet Adm Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, CHS 73-235,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM houser@mednet.ucla.edu FU Veterans Affairs Medical Research Funds; National Institutes of Health [NS046524] FX This work was supported by Veterans Affairs Medical Research Funds (C.R.H.) and National Institutes of Health grant NS046524 (C.R.H.). We thank Christine Farrar for conducting the Western blot analyses, Yliana Cetina for expert assistance with the seizure monitoring, and Drs. Tom O'Dell and Istvan Mody for helpful discussions. NR 66 TC 31 Z9 38 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD SEP 22 PY 2008 VL 156 IS 1 BP 222 EP 237 DI 10.1016/j.neuroscience.2008.07.010 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 352BE UT WOS:000259469300022 PM 18675888 ER PT J AU Webb, S Bortfeld, T AF Webb, S. Bortfeld, T. TI A new way of adapting IMRT delivery fraction-by-fraction to cater for variable intrafraction motion SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID PAIR OPTIMAL-CONTROL; ORGAN MOTION; CONFORMAL RADIOTHERAPY; MULTILEAF COLLIMATORS; MOVEMENT COMPENSATION; RADIATION-THERAPY; MOVING TARGET; OPTIMIZATION; PROFILES; PATTERN AB In this paper a technique is presented for adaptive therapy to compensate for variable intrafraction tissue motion. So long as the motion can be measured or deduced for each fraction the technique modifies the fluence profile for the subsequent fractions in a repeatable cyclic way. The fluence modification is based on projecting the dose discrepancies between the cumulative delivered dose after each fraction and the expected planned dose at the same stage. It was shown that, in general, it is best to adapt the fluence profile to moving leaves that also have been modified to 'breathe' according to some regular default motion. However, it is important to point out that, if this regular default motion were to differ too much from the variable motion at each fraction, then the result can be worse than adapting to non-breathing leaves in a dynamic MLC technique. Furthermore, in general it should always be possible to improve results by starting the adaptation process with a constrained deconvolution of the regular default motion. C1 [Webb, S.] Royal Marsden NHS Fdn Trust, Sutton SM2 5PT, Surrey, England. [Webb, S.; Bortfeld, T.] Inst Canc Res, Joint Dept Phys, Sutton SM2 5PT, Surrey, England. [Bortfeld, T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Webb, S (reprint author), Inst Canc Res, Joint Dept Phys, Downs Rd, Sutton SM2 5PT, Surrey, England. NR 30 TC 7 Z9 7 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 21 PY 2008 VL 53 IS 18 BP 5177 EP 5191 DI 10.1088/0031-9155/53/18/022 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 341QD UT WOS:000258728800022 PM 18728307 ER PT J AU Pawlicki, T Yoo, S Court, LE McMillan, SK Rice, RK Russell, JD Pacyniak, JM Woo, MK Basran, PS Boyer, AL Bonilla, C AF Pawlicki, Todd Yoo, Sua Court, Laurence E. McMillan, Sharon K. Rice, Roger K. Russell, J. Donald Pacyniak, John M. Woo, Milton K. Basran, Parminder S. Boyer, Arthur L. Bonilla, Claribel TI Process control analysis of IMRT QA: implications for clinical trials SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID QUALITY-ASSURANCE; IMPLEMENTATION; RADIOTHERAPY; PHANTOM; CANCER; DESIGN AB The purpose of this study is two-fold: first is to investigate the process of IMRT QA using control charts and second is to compare control chart limits to limits calculated using the standard deviation (sigma). Head and neck and prostate IMRT QA cases from seven institutions in both academic and community settings are considered. The percent difference between the point dose measurement in phantom and the corresponding result from the treatment planning system (TPS) is used for analysis. The average of the percent difference calculations defines the accuracy of the process and is called the process target. This represents the degree to which the process meets the clinical goal of 0% difference between the measurements and TPS. IMRT QA process ability defines the ability of the process to meet clinical specifications (e. g. 5% difference between the measurement and TPS). The process ability is defined in two ways: (1) the half-width of the control chart limits, and (2) the half-width of +/- 3 sigma limits. Process performance is characterized as being in one of four possible states that describes the stability of the process and its ability to meet clinical specifications. For the head and neck cases, the average process target across institutions was 0.3% (range: - 1.5% to 2.9%). The average process ability using control chart limits was 7.2% (range: 5.3% to 9.8%) compared to 6.7% (range: 5.3% to 8.2%) using standard deviation limits. For the prostate cases, the average process target across the institutions was 0.2% (range: - 1.8% to 1.4%). The average process ability using control chart limits was 4.4% (range: 1.3% to 9.4%) compared to 5.3% ( range: 2.3% to 9.8%) using standard deviation limits. Using the standard deviation to characterize IMRT QA process performance resulted in processes being preferentially placed in one of the four states. This is in contrast to using control charts for process characterization where the IMRT QA processes were spread over three of the four states with none of the processes in the ideal state. Control charts may be used for IMRT QA in clinical trials to categorize process performance, minimize protocol variation and guide process improvements. For the duration of an institution's participation in a protocol, updated control charts can be periodically sent to the protocol QA center to document continued process performance to protocol specifications. C1 [Pawlicki, Todd; Rice, Roger K.] Univ Calif San Diego, Dept Radiat Oncol, La Jolla, CA 92093 USA. [Yoo, Sua] Duke Univ, Dept Radiat Oncol, Durham, NC 27710 USA. [Court, Laurence E.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [McMillan, Sharon K.] Decatur Mem Hosp, Dept Radiat Oncol, Decatur, IL 62526 USA. [Russell, J. Donald] Community Canc Ctr, Roseburg, OR 97470 USA. [Pacyniak, John M.] Cox Hlth Syst, Hulston Canc Ctr, Springfield, MO 65807 USA. [Woo, Milton K.; Basran, Parminder S.] Odette Canc Ctr, Dept Med Phys, Toronto, ON, Canada. [Boyer, Arthur L.] Scott & White Mem Hosp & Clin, Temple, TX 76508 USA. [Bonilla, Claribel] Univ San Diego, Dept Ind & Syst Engn, San Diego, CA 92110 USA. RP Pawlicki, T (reprint author), Univ Calif San Diego, Dept Radiat Oncol, La Jolla, CA 92093 USA. EM tpaw@ucsd.edu NR 16 TC 19 Z9 21 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 21 PY 2008 VL 53 IS 18 BP 5193 EP 5205 DI 10.1088/0031-9155/53/18/023 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 341QD UT WOS:000258728800023 PM 18728311 ER PT J AU Smith, MR AF Smith, Matthew R. TI Osteoporosis in men with prostate cancer: Now for the fracture data SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; PREVENT BONE LOSS; HORMONE AGONISTS; ZOLEDRONIC ACID; CARCINOMA; RISK; PAMIDRONATE; BLOCKADE; PLACEBO C1 Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [K24 CA121990-03, K24 CA121990, K24 CA121990-04] NR 19 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2008 VL 26 IS 27 BP 4371 EP 4372 DI 10.1200/JCO.2008.17.9507 PG 2 WC Oncology SC Oncology GA 350KG UT WOS:000259350700004 PM 18802147 ER PT J AU Son, J Uchil, PD Kim, YB Shankar, P Kumar, P Lee, SK AF Son, Jiyeon Uchil, Pradeep D. Kim, Young Bong Shankar, Premlata Kumar, Priti Lee, Sang-Kyung TI Effective suppression of HIV-1 by artificial bispecific miRNA targeting conserved sequences with tolerance for wobble base-pairing SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE RNA interference; HIV; siRNA; shRNA; miRNA; conserved; lentivirus; wobble ID SHORT HAIRPIN RNAS; INTERFERENCE; SIRNA; REPLICATION; ESCAPE AB The high genetic diversity and mutability of HIV pose a major problem for RNAi-mediated antiviral therapy. Simultaneous targeting of multiple highly conserved viral sequences has been suggested for durable cross-clade inhibition. Here we validate the approach of co-targeting two conserved sequences in the Tat and Vif genes. When coexpressed as artificial microRNA from a PoIII driven miR-155-based vector, the sequences together mediated effective and Sustained inhibition of HIV replication without virus break-out. To understand the nature of this efficient control, we analyzed genome sequences of 625 HIV-1 isolates in the Los Alamos Sequence database. Interestingly most natural variants were capable of wobble binding with the Tat/Vif siRNAs. Efficient silencing of reporter luciferase constructs bearing these variants residues verified that the Tat/Vif sequences together tolerated wobble binding and mediated functional RNAi. We propose the rationale of targeting highly conserved HIV sequences where wobble substitutions permit functional RNAi for global HIV repression. (C) 2008 Elsevier Inc. All rights reserved. C1 [Shankar, Premlata; Kumar, Priti] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Shankar, Premlata; Kumar, Priti] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Son, Jiyeon; Lee, Sang-Kyung] Hanyang Univ, Dept Bioengn, Seoul 133791, South Korea. [Uchil, Pradeep D.] Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06510 USA. [Kim, Young Bong] Konkuk Univ, Dept Anim Biotechnol, Seoul 143701, South Korea. RP Kumar, P (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM kumar@idi.harvard.edu; sangkyunglee@hanyang.ac.kr RI Kumar, Priti/C-5699-2009 FU Hanyang University [HY-2005-N] FX We thank Hongseok Ban, Minsun Park, and Sunmi Choi for technical assistance. This work was supported by the Hanyang University Grant, HY-2005-N to S.K.L. NR 21 TC 12 Z9 16 U1 1 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 SEP 19 PY 2008 VL 374 IS 2 BP 214 EP 218 DI 10.1016/j.bbrc.2008.06.125 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 339TL UT WOS:000258600100008 PM 18619945 ER PT J AU Alvarez, D Vollmann, EH von Andrian, UH AF Alvarez, David Vollmann, Elisabeth H. von Andrian, Ulrich H. TI Mechanisms and consequences of dendritic cell migration SO IMMUNITY LA English DT Review ID EPIDERMAL LANGERHANS CELLS; SECONDARY LYMPHOID ORGANS; STEADY-STATE CONDITIONS; CADHERIN-MEDIATED ADHESION; HIGH ENDOTHELIAL VENULES; MICE LACKING EXPRESSION; NECROSIS-FACTOR-ALPHA; HOMING IN-VIVO; MEMORY T-CELLS; CHEMOKINE RECEPTOR AB Dendritic cells (DCs) are critical for adaptive immunity and tolerance. Most DCs are strategically positioned as immune sentinels poised to respond to invading pathogens in tissues throughout the body. Differentiated DCs and their precursors also circulate in blood and can get rapidly recruited to sites of challenge. Within peripheral tissues, DCs collect antigenic material and then traffic to secondary lymphoid organs, where they communicate with lymphocytes to orchestrate adaptive immune responses. Hence, the migration and accurate positioning of DCs is indispensable for immune surveillance. Here, we review the molecular traffic signals that govern the migration of DCs throughout their life cycle. C1 [Alvarez, David; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Vollmann, Elisabeth H.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM uva@hms.harvard.edu RI Alvarez, David/D-2992-2012; von Andrian, Ulrich/A-5775-2008 FU National Institutes of Health [R01 A1069259, R01 A1072252, P01 A1078897, P01 HL56949]; Canadian Institutes of Health Research; Austrian Academy of Sciences FX This work was supported, in part, by National Institutes of Health grants R01 A1069259, R01 A1072252, P01 A1078897, and P01 HL56949 (to U.H.v.A.), a fellowship from the Canadian Institutes of Health Research (to D.A.), and a fellowship from the Austrian Academy of Sciences (to E.H.V.). The authors would like to thank Irina Mazo, E. Ashley Moseman, and Silke Paust for helpful comments on the manuscript. NR 178 TC 207 Z9 222 U1 3 U2 30 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP 19 PY 2008 VL 29 IS 3 BP 325 EP 342 DI 10.1016/j.immuni.2008.08.006 PG 18 WC Immunology SC Immunology GA 355KX UT WOS:000259708900002 PM 18799141 ER PT J AU Cahill, CM Rogers, JT AF Cahill, Catherine M. Rogers, Jack T. TI Interleukin (IL) 1 beta induction of IL-6 is mediated by a novel phosphatidylinositol 3-kinase-dependent AKT/I kappa B kinase alpha pathway targeting activator protein-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INFLAMMATORY-BOWEL-DISEASE; INDUCED GENE-EXPRESSION; COLON-CARCINOMA CELLS; IKK-ALPHA; SIGNALING PATHWAY; UP-REGULATION; C-FOS; COLORECTAL-CANCER; EPITHELIAL-CELLS AB Here we describe a novel role for the phosphatidylinositol 3-kinase/AKT pathway in mediating induction of interleukin-6 (IL-6) in response to IL-1. Pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) inhibited IL-6 mRNA and protein production. Overexpression of either dominant-negative AKTor I kappa Bkinase alpha mutant, IKK alpha T23A, containing a mutation in a functional AKT phosphorylation site, shown previously to be important for NF kappa B activation, completely abrogated IL-6 promoter activation in response to IL-1. However, mutation of the consensus NF kappa B site on the IL-6 promoter did not abrogate promoter activation by IL-1 in contrast to the AP-1 site mutation. IL-1 induces phosphorylation of IKK alpha on the NF kappa B inducing kinase (NIK) phosphorylation sites Ser(176)/Ser(180) and on the Thr(23) site, and although phosphorylation of IKK alpha T23 is inhibited both by LY294002 and wortmannin, phosphorylation of Ser(176)/Ser(180) is not. Neither inhibition of PI 3-kinase/AKT nor IKK alpha T23A overexpression affected I kappa B alpha degradation in response to IL-1. Only partial inhibition by dominant-negative AKT and no inhibitory effect of IKK alpha T23A was observed on an IL-6 promoter-specific NF kappa B site in contrast to significant inhibitory effects on the AP-1 site. Taken together, we have discovered a novel PI 3-kinase/AKT-dependent pathway in response to IL-1, encompassing PI 3-kinase/AKT/IKK alpha T23 upstream of AP-1. This novel pathway is a parallel pathway to the PI 3-kinase/AKT upstream of NF kappa B and both are involved in IL-6 gene transcription in response to IL-1. C1 [Cahill, Catherine M.; Rogers, Jack T.] Massachusetts Gen Hosp East, Aging Res Unit, Charlestown, MA 02129 USA. [Cahill, Catherine M.; Rogers, Jack T.] Massachusetts Gen Hosp East, Neurochem Lab, Dept Psychiat Neurosci & Genet, Charlestown, MA 02129 USA. RP Cahill, CM (reprint author), MA Gen Hosp, CNY 149,Rm 2510,13th St, Charlestown, MA 02129 USA. EM ccahill@rics.bwh.harvard.edu FU National Institutes of Health [R01 AG20181] FX This work was supported, in whole or in part, by National Institutes of Health Grant R01 AG20181. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 86 TC 68 Z9 70 U1 0 U2 0 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 SEP 19 PY 2008 VL 283 IS 38 BP 25900 EP 25912 DI 10.1074/jbc.M707692200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 348GX UT WOS:000259200100017 PM 18515365 ER PT J AU Tan, KM Duquette, M Liu, JH Lawler, J Wang, JH AF Tan, Kemin Duquette, Mark Liu, Jin-huan Lawler, Jack Wang, Jia-huai TI The crystal structure of the heparin-binding reelin-N domain of F-spondin SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ECM protein; F-spondin; reelin-N domain; heparin binding; axon guidance ID AMYLOID PRECURSOR PROTEIN; CELL-ADHESION; EXTRACELLULAR-MATRIX; FLOOR PLATE; RECOGNITION; SUPERFAMILY; MOLECULE; GUIDANCE; CD2; INTEGRINS AB The extracellular matrix protein F-spondin mediates axon guidance during neuronal development. Its N-terminal domain, termed the reelin-N domain, is conserved in F-spondins, reelins, and other extracellular matrix proteins. In this study, a recombinant human reelin-N domain has been expressed, purified, and shown to bind heparin. The crystal structure of the reelin-N domain resolved to 2.0 angstrom reveals a variant immunoglobulin-like fold and potential heparin-binding sites. Substantial conformational variations even in secondary structure are observed between the two chemically identical reelin-N domains in one crystallographic asymmetric unit. The variations may result from extensive, highly specific interactions across the interface of the two reelin-N domains. The calculated values of buried surface area and the interface's shape complementarity are consistent with the formation of a weak dimer. The homophilic asymmetric dimer can potentially offer advantages in binding to ligands such as glycosaminoglycans, which may, in turn, bridge the two reelin-N domains and stabilize the dimer. Published by Elsevier Ltd. C1 [Tan, Kemin; Liu, Jin-huan; Wang, Jia-huai] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tan, Kemin; Liu, Jin-huan] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Tan, Kemin] Argonne Natl Lab, Biosci Div, Midwest Ctr Struct Genom, Argonne, IL 60439 USA. [Tan, Kemin] Argonne Natl Lab, Biosci Div, Struct Biol Ctr, Argonne, IL 60439 USA. [Duquette, Mark; Lawler, Jack] Beth Israel Deaconess Med Ctr, Dept Pathol, Div Canc Biol & Angiogenesis, Boston, MA 02215 USA. [Lawler, Jack] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Tan, KM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ktan@anl.gov FU National Heart, Lung and Blood Institute of the National Institutes of Health [HL49081, HL68003] FX We thank Florence Poy for help in cDNA pool preparation and Qunyan Lu for help in protein purification. This work was supported by a grant (HL49081 and HL68003) from the National Heart, Lung and Blood Institute of the National Institutes of Health to J.-H.W. and J.L. NR 39 TC 8 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 19 PY 2008 VL 381 IS 5 BP 1213 EP 1223 DI 10.1016/j.jmb.2008.06.045 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 347VJ UT WOS:000259169100011 PM 18602404 ER PT J AU Muller, FJ Laurent, LC Kostka, D Ulitsky, I Williams, R Lu, C Park, IH Rao, MS Shamir, R Schwartz, PH Schmidt, NO Loring, JF AF Mueller, Franz-Josef Laurent, Louise C. Kostka, Dennis Ulitsky, Igor Williams, Roy Lu, Christina Park, In-Hyun Rao, Mahendra S. Shamir, Ron Schwartz, Philip H. Schmidt, Nils O. Loring, Jeanne F. TI Regulatory networks define phenotypic classes of human stem cell lines SO NATURE LA English DT Article ID GENE-EXPRESSION PROFILES; HUMAN SOMATIC-CELLS; MICROARRAY DATA; CLASS DISCOVERY; MATRIX FACTORIZATION; BIOLOGICAL NETWORKS; PROGENITOR CELLS; GENOME-WIDE; DIFFERENTIATION; PLURIPOTENCY AB Stem cells are defined as self- renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal and adult sources have been called stem cells, even though they range from pluripotent cells - typified by embryonic stem cells, which are capable of virtually unlimited proliferation and differentiation - to adult stem cell lines, which can generate a far more limited repertoire of differentiated cell types. The rapid increase in reports of new sources of stem cells and their anticipated value to regenerative medicine(1,2) has highlighted the need for a general, reproducible method for classification of these cells(3). We report here the creation and analysis of a database of global gene expression profiles ( which we call the 'stem cell matrix') that enables the classification of cultured human stem cells in the context of a wide variety of pluripotent, multipotent and differentiated cell types. Using an unsupervised clustering method(4,5) to categorize a collection of similar to 150 cell samples, we discovered that pluripotent stem cell lines group together, whereas other cell types, including brain-derived neural stem cell lines, are very diverse. Using further bioinformatic analysis(6) we uncovered a protein - protein network (PluriNet) that is shared by the pluripotent cells ( embryonic stem cells, embryonal carcinomas and induced pluripotent cells). Analysis of published data showed that the PluriNet seems to be a common characteristic of pluripotent cells, including mouse embryonic stem and induced pluripotent cells and human oocytes. Our results offer a new strategy for classifying stem cells and support the idea that pluripotency and self- renewal are under tight control by specific molecular networks. C1 [Mueller, Franz-Josef; Laurent, Louise C.; Lu, Christina; Loring, Jeanne F.] Scripps Res Inst, Ctr Regenerat Med, La Jolla, CA 92037 USA. [Mueller, Franz-Josef] Univ Hosp Schleswig Holstein, Ctr Psychiat, ZIP Kiel, D-24105 Kiel, Germany. [Laurent, Louise C.] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92035 USA. [Kostka, Dennis] Max Planck Inst Mol Genet, Dept Computat Mol Biol, D-14195 Berlin, Germany. [Ulitsky, Igor; Shamir, Ron] Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Williams, Roy; Loring, Jeanne F.] Burnham Inst, La Jolla, CA 92037 USA. [Park, In-Hyun] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Park, In-Hyun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rao, Mahendra S.] Invitrogen Co, Frederick, MD 21704 USA. [Rao, Mahendra S.] Buck Inst Aging, Ctr Stem Cell Biol, Novato, CA 94945 USA. [Schwartz, Philip H.] Childrens Hosp Orange Cty, Res Inst, Ctr Res Neurosci, Orange, CA 92868 USA. [Schwartz, Philip H.] Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. [Schmidt, Nils O.] Univ Med Ctr Hamburg Eppendorf, Dept Neurosurg, D-20246 Hamburg, Germany. RP Muller, FJ (reprint author), Scripps Res Inst, Ctr Regenerat Med, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM fj.mueller@zip-kiel.de; jloring@scripps.edu RI MAller, Franz-Josef/E-3336-2010; Ulitsky, Igor/D-4828-2009; Schmidt, Nils Ole/D-5696-2014; OI Ulitsky, Igor/0000-0003-0555-6561 FU Christian- Abrechts University Young Investigator Award; Hamburger Krebsgesellschaft Grant; Edmond J. Safra Bioinformatics program fellowship at Tel- Aviv University (I.U.); Converging Technologies Program of The Israel Science Foundation [1767.07]; Raymond and Beverly Sackler Chair in Bioinformatics; Reproductive Scientist Development Program Scholar Award [K12 5K12HD000849-20]; California Institute for Regenerative Medicine Clinical Scholar Award [NIH P20 GM075059-01]; Alzheimer's Association; [SFB-654/C5] FX We thank C. Stubban, H. Dittmer, S. Zapf and H. Meissner for their work with various cell cultures. We are grateful to D. Wakeman, R. Gonzalez, S. McKercher, J. P. Lee, H.- S. Park and S. Y. Moon for sharing their cell preparations for the type collection. We are also grateful to R. Wesselschmidt and M. Pera for their unique GCT lines and G. Daley for providing human iPSCs. A. M. Kocabas and J. Cibelli shared their human oocyte expression data with us. A. Barsky let us use the Cerebral 2.0 plug- in before its publication. M. Rosentraeger helped to compile the cell culture metadata. We thank J. Aldenhoff, D. Hinze- Selch, M. Westphal, K. Lamszus, U. Kehler, D. Barker and A. Fritz for their support and discussions of this project. This study has been supported by the following grants and awards: Christian- Abrechts University Young Investigator Award (F.- J.M.), SFB-654/C5 Sleep and Plasticity (F.- J. M. and D. Hinze- Selch), Hamburger Krebsgesellschaft Grant (N.O.S.), Edmond J. Safra Bioinformatics program fellowship at Tel- Aviv University (I.U.), Converging Technologies Program of The Israel Science Foundation Grant No 1767.07 (R.S.), Raymond and Beverly Sackler Chair in Bioinformatics (R.S.), Reproductive Scientist Development Program Scholar Award K12 5K12HD000849-20 (L.C.L.), California Institute for Regenerative Medicine Clinical Scholar Award (L.C.L.), NIH P20 GM075059-01 (J.F.L.), the Alzheimer's Association (J.F.L.), and anonymous donations in support of stem cell research. NR 41 TC 205 Z9 206 U1 2 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 18 PY 2008 VL 455 IS 7211 BP 401 EP U55 DI 10.1038/nature07213 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 349EX UT WOS:000259265200047 PM 18724358 ER PT J AU Qi, HH Ongusaha, PP Myllyharju, J Cheng, DM Pakkanen, O Shi, YJ Lee, SW Peng, JM Shi, Y AF Qi, Hank H. Ongusaha, Pat P. Myllyharju, Johanna Cheng, Dongmei Pakkanen, Outi Shi, Yujiang Lee, Sam W. Peng, Junmin Shi, Yang TI Prolyl 4-hydroxylation regulates Argonaute 2 stability SO NATURE LA English DT Article ID MICRORNA-DEPENDENT LOCALIZATION; P-BODIES; PROTEIN; EXPRESSION; COLLAGEN; HYDROXYLASES; PROCOLLAGEN; DOMAIN; RISC; FORM AB Human Argonaute ( Ago) proteins are essential components of the RNA- induced silencing complexes ( RISCs). Argonaute 2 ( Ago2) has a P-element- induced wimpy testis ( PIWI) domain, which folds like RNase H and is responsible for target RNA cleavage in RNA interference(1). Proteins such as Dicer, TRBP, MOV10, RHA, RCK/p54 and KIAA1093 associate with Ago proteins and participate in small RNA processing, RISC loading and localization of Ago proteins in the cytoplasmic messenger RNA processing bodies(1,2). However, mechanisms that regulate RNA interference remain obscure. Here we report physical interactions between Ago2 and the alpha-(P4H-alpha(I)) and beta-(P4H-beta) subunits of the type I collagen prolyl- 4- hydroxylase (C-P4H( I)). Mass spectrometric analysis identified hydroxylation of the endogenous Ago2 at proline 700. In vitro, both Ago2 and Ago4 seem to be more efficiently hydroxylated than Ago1 and Ago3 by recombinant human C-P4H( I). Importantly, human cells depleted of P4H-alpha(I) or P4H-beta by short hairpin RNA and P4H-alpha(I) null mouse embryonic fibroblast cells showed reduced stability of Ago2 and impaired short interfering RNA programmed RISC activity. Furthermore, mutation of proline 700 to alanine also resulted in destabilization of Ago2, thus linking Ago2 P700 and hydroxylation at this residue to its stability regulation. These findings identify hydroxylation as a post- translational modification important for Ago2 stability and effective RNA interference. C1 [Qi, Hank H.; Ongusaha, Pat P.; Shi, Yujiang; Lee, Sam W.; Shi, Yang] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ongusaha, Pat P.; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. [Myllyharju, Johanna; Pakkanen, Outi] Univ Oulu, Oulu Ctr Cell Matrix Res, Bioctr Oulu, FIN-90014 Oulu, Finland. [Myllyharju, Johanna; Pakkanen, Outi] Univ Oulu, Dept Med Biochem & Mol Biol, FIN-90014 Oulu, Finland. [Cheng, Dongmei; Peng, Junmin] Emory Univ, Dept Human Genet, Ctr Neurodegenerat Dis, Sch Med, Atlanta, GA 30322 USA. [Shi, Yujiang] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02115 USA. [Shi, Yujiang] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, BCMP, Boston, MA 02115 USA. RP Shi, Y (reprint author), Harvard Univ, Sch Med, Dept Pathol, New Res Bldg 854,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM yang_shi@hms.harvard.edu FU Canadian Institute of Health Research; Health Science Council of the Academy of Finland [202469]; S. Juselius foundation; National Institutes of Health [AG025688, GM53874] FX We thank C. C. Mello, A. Grishok and P. A. Sharp for reading this manuscript and discussion. We thank E. Lehtimaki and R. Juntunen for in vitro hydroxylation assays, J. Lykke-Andersen and N. Kedersha for polyclonal anti-Dcp1a antibody and anti-Tia1 antibody, and the personnel of the Biocenter Oulu Transgenic Animal Core Facility and the University of Oulu Laboratory Animal Centre for technical assistance. We also thank the Kazusa DNA Research Institute (Japan) for providing the KIAA clones with numbers 1567, 1093, 1582 and 1460 and N. R. Wall for pOZ-FH-Ago1 plasmid. H. H. Q. was supported by a Canadian Institute of Health Research postdoctoral fellowship. This work was supported by grants from the Health Science Council of the Academy of Finland (202469) and the S. Juselius foundation to J. M. and National Institutes of Health grants to J. P. (AG025688) and Y.S. (GM53874). NR 26 TC 120 Z9 126 U1 3 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 18 PY 2008 VL 455 IS 7211 BP 421 EP U78 DI 10.1038/nature07186 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 349EX UT WOS:000259265200051 PM 18690212 ER PT J AU Goldstein, MA Herzog, DB Misra, M Sagar, P Broder, J Palmer, BA Riggs, S AF Goldstein, Mark A. Herzog, David B. Misra, Madhusmita Sagar, Pallavi Broder, Jennifer Palmer, Brian A. Riggs, Susanne TI A man with weight loss and abdominal pain - Anorexia nervosa, with fecal impaction, bradycardia, delayed bone maturation, short stature, low bone density, and cerebral atrophy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OF-THE-LITERATURE; EATING-DISORDERS; ADOLESCENT GIRLS; GROWTH-HORMONE; METABOLISM; COMPLICATIONS; COMORBIDITY; OUTPATIENTS; TUMORS; MALES C1 [Goldstein, Mark A.; Herzog, David B.; Misra, Madhusmita] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Herzog, David B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sagar, Pallavi] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Goldstein, Mark A.; Herzog, David B.; Misra, Madhusmita; Sagar, Pallavi; Broder, Jennifer; Palmer, Brian A.; Riggs, Susanne] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Goldstein, MA (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. FU Tercica FX Dr. Misra reports receiving grant support from Tercica. No other potential conflict of interest relevant to this article was reported. NR 42 TC 8 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 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 18 PY 2008 VL 359 IS 12 BP 1272 EP 1283 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 349DV UT WOS:000259259900013 PM 18799562 ER PT J AU Ou, WB Zhu, MJ Demetri, GD Fletcher, CDM Fletcher, JA AF Ou, W-b Zhu, M-j Demetri, G. D. Fletcher, C. D. M. Fletcher, J. A. TI Protein kinase C-theta regulates KIT expression and proliferation in gastrointestinal stromal tumors SO ONCOGENE LA English DT Article DE PRKCQ; KIT; shRNA; gastrointestinal neoplasm; sarcoma; imatinib ID RECEPTOR TYROSINE KINASES; KAPPA-B ACTIVATION; RETINOID-X-RECEPTOR; T-CELL-ACTIVATION; PKC-THETA; INTESTINAL EPITHELIUM; ANTICANCER THERAPY; IMATINIB MESYLATE; MOLECULAR-CLONING; GENE-EXPRESSION AB Oncogenic KIT or PDGFRA receptor tyrosine kinase mutations are compelling therapeutic targets in gastrointestinal stromal tumors (GISTs), and the KIT/PDGFRA kinase inhibitor, imatinib, is standard of care for patients with metastatic GIST. However, most of these patients eventually develop clinical resistance to imatinib and other KIT/PDGFRA kinase inhibitors and there is an urgent need to identify novel therapeutic strategies. We reported previously that protein kinase C-theta (PKC theta) is activated in GIST, irrespective of KIT or PDGFRA mutational status, and is expressed at levels unprecedented in other mesenchymal tumors, therefore serving as a diagnostic marker of GIST. Herein, we characterize biological functions of PKC theta in imatinib-sensitive and imatinib-resistant GISTs, showing that lentivirus-mediated PKC theta knockdown is accompanied by inhibition of KIT expression in three KIT+/PKC theta+ GIST cell lines, but not in a comparator KIT+/PKCh theta-Ewing's sarcoma cell line. PKC theta knockdown in the KIT+ GISTs was associated with inhibition of the phosphatidylinositol-3-kinase/AKT signaling pathway, upregulation of the cyclin-dependent kinase inhibitors p21 and p27, antiproliferative effects due to G(1) arrest and induction of apoptosis, comparable to the effects seen after direct knockdown of KIT expression by KIT short-hairpin RNA. These novel findings highlight that PKC theta warrants clinical evaluation as a potential therapeutic target in GISTs, including those cases containing mutations that confer resistance to KIT/PDGFRA kinase inhibitors. C1 [Ou, W-b; Zhu, M-j; Fletcher, C. D. M.; Fletcher, J. A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Demetri, G. D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. [Demetri, G. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ou, WB (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM wou@rics.bwh.harvard.edu; jfletcher@partners.org FU GI SPORE [1P50CA127003-01]; Life Raft Group; Cesarini Team for the Pan-Massachusetts Challenge; Virginia and Daniel K Ludwig Trust for Cancer Research; Ronald O Perelman Fund; Stutman GIST Cancer Research Fund; Rubenstein Foundation FX This work was supported by grants from an anonymous donor, GI SPORE 1P50CA127003-01, the Life Raft Group, Cesarini Team for the Pan-Massachusetts Challenge, the Virginia and Daniel K Ludwig Trust for Cancer Research, the Ronald O Perelman Fund for Cancer Research, the Stutman GIST Cancer Research Fund, the Rubenstein Foundation and Leslie's Links. We thank Sarah E Bulmer and William Hahn for providing shRNA constructs. NR 54 TC 42 Z9 44 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 SEP 18 PY 2008 VL 27 IS 42 BP 5624 EP 5634 DI 10.1038/onc.2008.177 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 349KX UT WOS:000259280800008 PM 18521081 ER PT J AU Modlin, IM Moss, SF Chung, DC Jensen, RT Snyderwine, E AF Modlin, Irvin M. Moss, Steven F. Chung, Daniel C. Jensen, Robert T. Snyderwine, Elizabeth TI Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; CARCINOID-TUMORS; MOLECULAR-GENETICS; GRADING SYSTEM; HEART-DISEASE; CELLS; CLASSIFICATION; SOMATOSTATIN; INTESTINE; MASTOMYS AB A National Cancer Institute summit meeting on gastroenteropancreatic neuroendocrine and carcinoid tumors was held in September 2007 to present the currently accepted standards of care for patients with these tumors and to identify areas requiring investigation and development. These tumors are clinically and pathologically heterogeneous, present commonly with obscure symptoms that lead to delays in diagnosis of years, and have an incidence in the United States of 2.5 to 5 cases per 100 000. The 5-year survival rates range between 15% and 95%, depending on the site and extent of disease. This report delineates the main conclusions of the meeting, including the best practice diagnosis and treatment strategies for gastropancreatic neuroendocrine tumors, and the identification of clinical and scientific areas that are most in need of attention. The most pressing needs were public and physician education, identification of molecular markers for early diagnosis and therapeutic monitoring, improved imaging modalities and molecular prognostication, development of a standardized pathological classification system, and creation of regional centers of expertise with tumor and laboratory data banks. In addition, adequately validated neuroendocrine tumor models and cell lines should be established to investigate the molecular mechanisms involved in the control of their growth and secretion, and to facilitate the development of specific therapies that should be examined in well-designed multicenter studies of defined patient groups. C1 [Modlin, Irvin M.] Yale Univ, Sch Med, Dept Surg Gastroenterol, New Haven, CT 06520 USA. [Moss, Steven F.] Brown Univ, Rhode Isl Hosp, Providence, RI 02912 USA. [Chung, Daniel C.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02115 USA. [Jensen, Robert T.] NIDDK, Digest Dis Branch, Bethesda, MD USA. [Snyderwine, Elizabeth] NCI, NIH, Bethesda, MD 20892 USA. RP Modlin, IM (reprint author), Yale Univ, Sch Med, Dept Surg Gastroenterol, POB 208062, New Haven, CT 06520 USA. EM imodlin@optonline.net FU National Cancer Institute of the Director; National Institutes of Health (NIH) office of Rare Diseases; National Cancer Institute Division of Cancer Biology; Foundation for the National Institutes of Health (FNIH) FX Funding and other support for the conference was provided by the National Cancer Institute office of the Director, the National Institutes of Health (NIH) office of Rare Diseases, the National Cancer Institute Division of Cancer Biology, and the Foundation for the National Institutes of Health (FNIH). FNIH, an independent nonprofit organization, supports the mission of the NIH by linking the generosity of private sector donors and partners to NIH programs. The FNIH partnership with the Neuroendocrine Tumor- Carcinoid Summit Conference was substantially supported by Tercica, Ipsen, Novartis, Covidien, Molecular Insight Pharmaceuticals, and individual donations from the Capital Area Carcinoid Survivors, the Carcinoid Cancer Foundation, and the Caring for Carcinoid Foundation. NR 49 TC 112 Z9 115 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 17 PY 2008 VL 100 IS 18 BP 1282 EP 1289 DI 10.1093/jnci/djn275 PG 8 WC Oncology SC Oncology GA 350BR UT WOS:000259328000007 PM 18780869 ER PT J AU Bilimoria, KY Bentrem, DJ Stewart, AK Talamonti, MS Winchester, DP Russell, TR Ko, CY AF Bilimoria, Karl Y. Bentrem, David J. Stewart, Andrew K. Talamonti, Mark S. Winchester, David P. Russell, Thomas R. Ko, Clifford Y. TI Lymph node evaluation as a colon cancer quality measure: A national hospital report card SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID COLORECTAL-CANCER; MINIMUM NUMBER; SURVIVAL; RESECTION; SURGERY; SPECIMENS; OUTCOMES; RECOMMENDATIONS; PROGNOSIS; VOLUME AB Background Examination of 12 or more regional lymph nodes for colon cancer is associated with improved staging and survival, and the National Quality Forum recently endorsed lymph node examination for colon cancer as a quality surveillance measure. However, information regarding the extent of hospital compliance with the 12-node measure in the United States is lacking. Methods From the National Cancer Data Base, 1296 hospitals that performed 156 789 colectomies in 1996-1997 and 2004-2005 were identified, and rates of hospital-level compliance (defined as examination of >= 12 nodes in >= 75% of patients) in these two time periods were compared. Multivariable models were developed to determine if hospital type, volume, or differences in case mix were associated with 12-node measure compliance. All statistical tests were two-sided. Reults In 1996-1997, 15% of hospitals were compliant with the 12-node measure; in 2004-2005 the percentage of compliant hospitals had increased to 38%. From 1996-1997 to 2004-2005, 12-node measure compliance increased at 980 hospitals, remained unchanged at 6 hospitals, and decreased at 310 hospitals. In 2004-2005, National Cancer Institute-designated Comprehensive Cancer Centers were more frequently compliant with the 12-node measure than other academic hospitals, Veterans' Administration hospitals, or community hospitals (78.1% versus 52.4%, 53.1%, and 33.7%, respectively, all P < .001), even after adjustment for differences in characteristics of the colon cancer patients at these hospitals. Conclusions This study provides a national report card of nearly 1300 hospitals showing that more than 60% of institutions failed to achieve a compliance benchmark for the 12-node measure. Considerable improvement is needed in colon cancer nodal evaluation in the United States. C1 [Bilimoria, Karl Y.; Stewart, Andrew K.; Winchester, David P.; Russell, Thomas R.; Ko, Clifford Y.] Amer Coll Surg, Canc Programs, Chicago, IL 60611 USA. [Bilimoria, Karl Y.; Bentrem, David J.; Talamonti, Mark S.; Winchester, David P.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL USA. [Talamonti, Mark S.; Winchester, David P.] Evanston NW Healthcare, Dept Surg, Evanston, IL USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Canc Programs, 633 N St Clair St,25th Floor, Chicago, IL 60611 USA. EM kbilimoria@facs.org FU American College of Surgeons; Clinical Scholars in Residence program; American Cancer Society [ACS IRG 93-037-12]; National Cancer Institute [NCI-60058-NE] FX American College of Surgeons, Clinical Scholars in Residence program (to K. Y. B.); American Cancer Society (ACS IRG 93-037-12 to D. J. B.); National Cancer Institute (NCI-60058-NE to C. Y. K.). NR 42 TC 106 Z9 108 U1 1 U2 4 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 SEP 17 PY 2008 VL 100 IS 18 BP 1310 EP 1317 DI 10.1093/jnci/djn293 PG 8 WC Oncology SC Oncology GA 350BR UT WOS:000259328000010 PM 18780863 ER PT J AU Van den Stock, J van de Riet, WAC Righart, R de Gelder, B AF Van den Stock, Jan van de Riet, Wim A. C. Righart, Ruthger de Gelder, Beatrice TI Neural Correlates of Perceiving Emotional Faces and Bodies in Developmental Prosopagnosia: An Event-Related fMRI-Study SO PLOS ONE LA English DT Article AB Many people experience transient difficulties in recognizing faces but only a small number of them cannot recognize their family members when meeting them unexpectedly. Such face blindness is associated with serious problems in everyday life. A better understanding of the neuro-functional basis of impaired face recognition may be achieved by a careful comparison with an equally unique object category and by a adding a more realistic setting involving neutral faces as well facial expressions. We used event-related functional magnetic resonance imaging (fMRI) to investigate the neuro-functional basis of perceiving faces and bodies in three developmental prosopagnosics (DP) and matched healthy controls. Our approach involved materials consisting of neutral faces and bodies as well as faces and bodies expressing fear or happiness. The first main result is that the presence of emotional information has a different effect in the patient vs. the control group in the fusiform face area (FFA). Neutral faces trigger lower activation in the DP group, compared to the control group, while activation for facial expressions is the same in both groups. The second main result is that compared to controls, DPs have increased activation for bodies in the inferior occipital gyrus (IOG) and for neutral faces in the extrastriate body area (EBA), indicating that body and face sensitive processes are less categorically segregated in DP. Taken together our study shows the importance of using naturalistic emotional stimuli for a better understanding of developmental face deficits. C1 [Van den Stock, Jan; van de Riet, Wim A. C.; Righart, Ruthger; de Gelder, Beatrice] Tilburg Univ, Lab Cognit & Affect Neurosci, NL-5000 LE Tilburg, Netherlands. [Van den Stock, Jan] Univ Hosp Leuven, Old Age Psychiat Dept, Louvain, Belgium. [de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Van den Stock, J (reprint author), Tilburg Univ, Lab Cognit & Affect Neurosci, NL-5000 LE Tilburg, Netherlands. EM degelder@nmr.mgh.harvard.edu RI Van den Stock, Jan/F-1906-2014 OI Van den Stock, Jan/0000-0001-5756-3195 FU Human Frontiers Science Program [RGP0054/2004-C]; European Commission [FP6-2005-NEST-Path Imp 043403-COBOL]; NWO, Dutch Science Foundation FX The research was partly funded by a Human Frontiers Science Program grant (RGP0054/2004-C), a European Commission grant (FP6-2005-NEST-Path Imp 043403-COBOL) and a NWO grant (Dutch Science Foundation). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 77 TC 33 Z9 33 U1 5 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 17 PY 2008 VL 3 IS 9 AR e3195 DI 10.1371/journal.pone.0003195 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 422LB UT WOS:000264428200002 PM 18797499 ER PT J AU Lee, TA Pickard, AS Au, DH Bartle, B Weiss, KB AF Lee, Todd A. Pickard, A. Simon Au, David H. Bartle, Brian Weiss, Kevin B. TI Risk for death associated with medications for recently diagnosed chronic obstructive pulmonary disease SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID INHALED CORTICOSTEROIDS; BIASED SELECTION; MORTALITY; COPD; HEALTH; HOSPITALIZATIONS; EXACERBATIONS; METAANALYSIS; FLUTICASONE; IPRATROPIUM AB Background: Concerns exist regarding increased risk for mortality associated with some chronic obstructive pulmonary disease (COPD) medications. Objective: To examine the association between various respiratory medications and risk for death in veterans with newly diagnosed COPD. Design: Nested case - control study in a cohort identified between 1 October 1999 and 30 September 2003 and followed through 30 September 2004 by using National Veterans Affairs inpatient, outpatient, pharmacy, and mortality databases; Centers for Medicare & Medicaid Services databases; and National Death Index Plus data. Cause of death was ascertained for a random sample of 40% of those who died during follow-up. Case patients were categorized on the basis of all-cause, respiratory, or cardiovascular death. Mortality risk associated with medications was assessed by using conditional logistic regression adjusted for comorbid conditions, health care use, and markers of COPD severity. Setting: U. S. Veterans Health Administration health care system. Participants: 32 130 case patients and 320 501 control participants in the all-cause mortality analysis. Of 11 897 patients with cause-of-death data, 2405 case patients had respiratory deaths and 3159 case patients had cardiovascular deaths. Measurements: All-cause mortality; respiratory and cardiovascular deaths; and exposure to COPD medications, inhaled corticosteroids, ipratropium, long-acting beta-agonists, and theophylline in the 6 months preceding death. Results: Adjusted odds ratios (ORs) for all-cause mortality were 0.80 (95% CI, 0.78 to 0.83) for inhaled corticosteroids, 1.11 ( CI, 1.08 to 1.15) for ipratropium, 0.92 (CI, 0.88 to 0.96) for long-acting beta-agonists, and 1.05 (CI, 0.99 to 1.10) for theophylline. Ipratropium was associated with increased cardiovascular deaths (OR, 1.34 [CI, 1.22 to 1.47]), whereas inhaled corticosteroids were associated with reduced risk for cardiovascular death ( OR, 0.80 [ CI, 0.72 to 0.88]). Results were consistent across sensitivity analyses. Limitations: Current smoking status and lung function were not measured. Misclassification of cause-specific mortality is unknown. Conclusion: The possible association between ipratropium and elevated risk for all-cause and cardiovascular death needs further study. C1 [Lee, Todd A.] Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. NW Univ Feinberg, Sch Med, Chicago, IL USA. Univ Illinois, Chicago, IL USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Amer Board Med Specialties, Evanston, IL USA. RP Lee, TA (reprint author), Vet Affairs Edward Hines Jr Hosp, 5000 S 5th Ave,151-H, Hines, IL 60141 USA. EM todd.lee@va.gov FU the U. S. Department of Veterans Affairs Health Services Research and Development [IIR 03-307] FX By the U. S. Department of Veterans Affairs Health Services Research and Development (IIR 03-307). NR 38 TC 124 Z9 127 U1 0 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 16 PY 2008 VL 149 IS 6 BP 380 EP W73 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 348SM UT WOS:000259230200002 PM 18794557 ER PT J AU Qaseem, A Snow, V Shekelle, P Hopkins, R Forciea, MA Owens, DK AF Qaseem, Amir Snow, Vincenza Shekelle, Paul Hopkins, Robert, Jr. Forciea, Mary Ann Owens, Douglas K. CA Clinical Efficacy Assessment Subco TI Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: A clinical practice guideline from the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; CORTICOSTEROID-INDUCED OSTEOPOROSIS; CYCLICAL ETIDRONATE THERAPY; VITAMIN-D SUPPLEMENTATION; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; HEALTHY POSTMENOPAUSAL WOMEN; HORMONE REPLACEMENT THERAPY; PRIMARY BILIARY-CIRRHOSIS; ESTROGEN PLUS PROGESTIN AB Description: The American College of Physicians (ACP) developed this guideline to present the available evidence on various pharmacologic treatments to prevent fractures in men and women with low bone density or osteoporosis. Methods: Published literature on this topic was identified by using MEDLINE (1966 to December 2006), the ACP Journal Club database, the Cochrane Central Register of Controlled Trials (no date limits), the Cochrane Database of Systematic Reviews (no date limits), Web sites of the United Kingdom National Institute of Health and Clinical Excellence (no date limits), and the United Kingdom Health Technology Assessment Program (January 1998 to December 2006). Searches were limited to English-language publications and human studies. Keywords for search included terms for osteoporosis, osteopenia, low bone density, and the drugs listed in the key questions. This guideline grades the evidence and recommendations according to the ACP's clinical practice guidelines grading system. C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Santa Monica, CA USA. RAND, Santa Monica, CA USA. Univ Arkansas, Little Rock, AR 72204 USA. Stanford Univ, Stanford, CA 94305 USA. Vet Affairs Palo Alto Hlth Care Syst, Stanford, CA USA. RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA. EM aqaseem@acponline.org FU the American College of Physicians' operating budget FX Financial support for the development of this guideline comes exclusively from the American College of Physicians' operating budget. NR 151 TC 95 Z9 96 U1 1 U2 5 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 SEP 16 PY 2008 VL 149 IS 6 BP 404 EP W77 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 348SM UT WOS:000259230200005 PM 18794560 ER PT J AU Vetting, MW Park, CH Hegde, SS Jacoby, GA Hooper, DC Blanchard, JS AF Vetting, Matthew W. Park, Chi Hye Hegde, Subray S. Jacoby, George A. Hooper, David C. Blanchard, John S. TI Mechanistic and structural analysis of aminoglycoside N-acetyltransferase AAC(6 ')-Ib and its bifunctional, fluoroquinolone-active AAC(6 ')-Ib-cr variant SO BIOCHEMISTRY LA English DT Article ID MEDIATED QUINOLONE RESISTANCE; ANTIBIOTIC-RESISTANCE; MODIFYING ENZYME; SUBSTRATE-SPECIFICITY; KINETIC MECHANISM; CONSERVED REGION; PLASMID; EMERGENCE; RESIDUES AB Enzymatic modification of aminoglycoside antibiotics mediated by regioselective aminoglycoside N-acetyltransferases is the predominant cause of bacterial resistance to aminoglycosides. A recently discovered bifunctional aminoglycoside acetyltransferase (AAC(6')-Ib variant, AAC(6')-Ib-cr) has been shown to catalyze the acetylation of fluoroquinolones as well as aminoglycosides. We have expressed and purified AAC(6')-Ib-wt and its bifunctional variant AAC(6')-Ib-cr in Escherichia coli and characterized their kinetic and chemical mechanism. Initial velocity and dead-end inhibition studies support an ordered sequential mechanism for the enzyme(s). The three-dimensional structure of AAC(6')-Ib-wt was determined in various complexes with donor and acceptor ligands to resolutions greater than 2.2 angstrom. Observation of the direct, and optimally positioned, interaction between the 6'-NH(2) and Asp 115 suggests that Asp 115 acts as a general base to accept a proton in the reaction. The structure of AAC(6')-Ib-wt permits the construction of a molecular model of the interactions of fluoroquinolones with the AAC(6')-Ib-cr variant. The model suggests that a major contribution to the fluoroquinolone acetylation activity comes from the Asp179Tyr mutation, where Tyr179 makes pi-stacking interactions with the quinolone ring facilitating quinolone binding. The model also suggests that fluoroquinolones and aminoglycosides have different binding modes. On the basis of kinetic properties, the pH dependence of the kinetic parameters, and structural information, we propose an acid/base-assisted reaction catalyzed by AAC(6')-Ib-wt and the AAC(6')-Ib-cr variant involving a ternary complex. C1 [Vetting, Matthew W.; Hegde, Subray S.; Blanchard, John S.] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. [Park, Chi Hye; Hooper, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis,GRJ 512, Boston, MA 02114 USA. [Jacoby, George A.] Lahey Clin Fdn, Burlington, MA 01805 USA. RP Blanchard, JS (reprint author), Albert Einstein Coll Med, Dept Biochem, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM blanchar@aecom.yu.edu FU NIAID NIH HHS [R01 AI043312, AI043312, AI057576, R01 AI057576, R01 AI060899, R01 AI060899-05, T32 AI007501, T32 AI07501]; PHS HHS [A160899] NR 44 TC 51 Z9 57 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 16 PY 2008 VL 47 IS 37 BP 9825 EP 9835 DI 10.1021/bi800664x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 347CU UT WOS:000259119000012 PM 18710261 ER PT J AU Yan, BP Kiernan, TJ Gupta, V Schainfeld, RM Garasic, JM AF Yan, Bryan P. Kiernan, Thomas J. Gupta, Vishal Schainfeld, Robert M. Garasic, Joseph M. TI Over rehearsed - A cellist with Paget-Schroetter SO CIRCULATION LA English DT Editorial Material C1 [Yan, Bryan P.] Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yan, BP (reprint author), Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med, 55 Fruit St,GRB-800, Boston, MA 02114 USA. EM bryan.p.yan@gmail.com RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015 NR 1 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 16 PY 2008 VL 118 IS 12 BP E160 EP E161 DI 10.1161/CIRCULATIONAHA.108.777961 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 348QK UT WOS:000259224800014 PM 18794397 ER PT J AU Gomperts, SN Rentz, DM Moran, E Becker, JA Locascio, JJ Klunk, WE Mathis, CA Elmaleh, DR Shoup, T Fischman, AJ Hyman, BT Growdon, JH Johnson, KA AF Gomperts, S. N. Rentz, D. M. Moran, E. Becker, J. A. Locascio, J. J. Klunk, W. E. Mathis, C. A. Elmaleh, D. R. Shoup, T. Fischman, A. J. Hyman, B. T. Growdon, J. H. Johnson, K. A. TI Imaging amyloid deposition in Lewy body diseases SO NEUROLOGY LA English DT Article ID PITTSBURGH COMPOUND-B; PRECLINICAL ALZHEIMERS-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; PARKINSONS-DISEASE; COGNITIVE IMPAIRMENT; CEREBRAL-CORTEX; DEMENTIA; BODIES; DIAGNOSIS; PATHOLOGY AB Background: Extrapyramidal motor symptoms precede dementia in Parkinson disease (PDD) by many years, whereas dementia occurs early in dementia with Lewy bodies (DLB). Despite this clinical distinction, the neuropsychological and neuropathologic features of these conditions overlap. In addition to widespread distribution of Lewy bodies, both diseases have variable burdens of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer disease (AD). Objectives: To determine whether amyloid deposition, as assessed by PET imaging with the beta-amyloid-binding compound Pittsburgh Compound B (PiB), can distinguish DLB from PDD, and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features. Methods: Eight DLB, 7 PDD, 11 Parkinson disease (PD), 15 AD, and 37 normal control (NC) subjects underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio. Results: Cortical amyloid burden was higher in the DLB group than in the PDD group, comparable to the AD group. Amyloid deposition in the PDD group was low, comparable to the PD and NC groups. Relative to global cortical retention, occipital PiB retention was lower in the AD group than in the other groups. For the DLB, PDD, and PD groups, amyloid deposition in the parietal (lateral and precuneus)/posterior cingulate region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function. Conclusions: Global cortical amyloid burden is high in dementia with Lewy bodies (DLB) but low in Parkinson disease dementia. These data suggest that beta-amyloid may contribute selectively to the cognitive impairment of DLB and may contribute to the timing of dementia relative to the motor signs of parkinsonism. C1 [Gomperts, S. N.; Moran, E.; Becker, J. A.; Locascio, J. J.; Elmaleh, D. R.; Shoup, T.; Fischman, A. J.; Hyman, B. T.; Growdon, J. H.; Johnson, K. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gomperts, S. N.; Rentz, D. M.; Locascio, J. J.; Elmaleh, D. R.; Hyman, B. T.; Growdon, J. H.; Johnson, K. A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rentz, D. M.; Johnson, K. A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Locascio, J. J.] MIT, Cambridge, MA 02139 USA. [Klunk, W. E.; Mathis, C. A.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Johnson, KA (reprint author), Div Nucl Med & Mol Imaging, 55 Fruit St, Boston, MA 02114 USA. EM kajohnson@partners.org RI Mathis, Chester/A-8607-2009; OI Klunk, William/0000-0001-5512-0251 FU Alzheimer's Disease Research Center (ADRC) [P50-AG05134]; Harvard Neurodiscovery Center; Udall PD Center [P50-NS38372]; Alzheimer Association [IIRG-0626331]; [R21-NS060310]; [R01 AG018402]; [R37 AG025516]; [P50 AG05133]; [3R01AG027435-02S1]; [P01 AG025204] FX Supported by grants from the Alzheimer's Disease Research Center (ADRC) and Harvard Neurodiscovery Center (S.N.G., K.A.J.), Udall PD Center (P50-NS38372; J.H.G.), ADRC (P50-AG05134; J.H.G., K.A.J.), R21-NS060310 (S.N.G., J.H.G., K.A.J.), the Alzheimer Association (IIRG-0626331; K.A.J.), R01 AG018402 (W.E.K., C.A.M.), R37 AG025516 (W.E.K., C.A.M.), P50 AG05133 (W.E.K., C.A.M.), 3R01AG027435-02S1 (K.A.J.), and P01 AG025204 (W.E.K., C.A.M.). NR 41 TC 234 Z9 244 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 16 PY 2008 VL 71 IS 12 BP 903 EP 910 DI 10.1212/01.wnl.0000326146.60732.d6 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 348MS UT WOS:000259215200007 PM 18794492 ER PT J AU Guerau-De-Arellano, M Mathis, D Benoist, C AF Guerau-de-Arellano, Mireia Mathis, Diane Benoist, Christophe TI Transcriptional impact of Aire varies with cell type SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; tissue ID THYMIC EPITHELIAL-CELLS; GENE-EXPRESSION; CENTRAL TOLERANCE; DEFICIENT MICE; TARGET GENES; AUTOIMMUNITY; ANTIGEN; MECHANISM; PROTEIN; GENOME AB Aire promotes T cell tolerance by inducing the expression of a broad swath of genes encoding peripheral tissue antigens (PTAs) in medullary epithelial cells (MECs) of the thymus. The exact mechanism used in inducing this ectopic transcription remains obscure. To address this issue, we generated transgenic mice expressing Aire in pancreatic islet beta cells. Gene-expression profiling of such islets revealed that Aire can have a significant impact on transcription in these cells, mainly inducing, but also repressing, transcript levels in a manner comparable with its influence on MECs. The exact transcripts affected differed in MECs and beta cells, with limited overlap between the two sets of Aire-modulated genes. We propose that Aire promotes ectopic gene expression by a generic mechanism that does not depend on any particular characteristics or transcription mechanisms operating in MECs, whereas the cellular environment does govern which genes are actually susceptible to Aire regulation. C1 [Guerau-de-Arellano, Mireia; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU National Institutes of Health [R01 DK60027]; Young Chair funds; Joslin Diabetes Center's National Institute of Diabetes and Digestive and Kidneys Diseases; Endocrinology Research Center FX We acknowledge the expert help of John Stockton (for the manipulated NOD mouse core data) and Vaja Tchipashvili (for the mouse islet core data) of the Juvenile Diabetes Research Foundation Center for Immune Tolerance in Diabetes at Harvard University; Dr. Emily Venanzi for the NOD MEC microarray data; and Rachel Melamed, Scott Davis, Vanessa Tran, Kimie Hattori and Ella Hyatt for help with the computational data analysis and mice. This work was supported by National Institutes of Health Grant R01 DK60027 and Young Chair funds (to D.M. and C.B.), and by the Joslin Diabetes Center's National Institute of Diabetes and Digestive and Kidneys Diseases-funded Diabetes and Endocrinology Research Center. NR 25 TC 35 Z9 36 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 SEP 16 PY 2008 VL 105 IS 37 BP 14011 EP 14016 DI 10.1073/pnas.0806616105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 351QG UT WOS:000259438500060 PM 18780794 ER PT J AU Bloushtain-Qimron, N Yao, J Snyder, EL Shipitsin, M Campbell, LL Mani, SA Hua, M Chen, HY Ustyansky, V Antosiewicz, JE Argani, P Halushka, MK Thomson, JA Pharoah, P Porgador, A Sukumar, S Parsons, R Richardson, AL Stampfer, MR Gelman, RS Nikolskaya, T Nikolsky, Y Polyak, K AF Bloushtain-Qimron, Noga Yao, Jun Snyder, Eric L. Shipitsin, Michail Campbell, Lauren L. Mani, Sendurai A. Hua, Min Chen, Haiyan Ustyansky, Vadim Antosiewicz, Jessica E. Argani, Pedram Halushka, Marc K. Thomson, James A. Pharoah, Paul Porgador, Angel Sukumar, Saraswati Parsons, Ramon Richardson, Andrea L. Stampfer, Martha R. Gelman, Rebecca S. Nikolskaya, Tatiana Nikolsky, Yuri Polyak, Kornelia TI Cell type-specific DNA methylation patterns in the human breast SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; differentiation; progenitor; stem cell ID EMBRYONIC STEM-CELLS; IN-VITRO; CANCER; DIFFERENTIATION; POLYCOMB; TRANSFORMATION; EXPRESSION; HIERARCHY; NETWORKS; ROLES AB Cellular identity and differentiation are determined by epigenetic programs. The characteristics of these programs in normal human mammary epithelium and their similarity to those in stem cells are unknown. To begin investigating these issues, we analyzed the DNA methylation and gene expression profiles of distinct subpopulations of mammary epithelial cells by using MSDK (methylation-specific digital karyotyping) and SAGE (serial analysis of gene expression). We identified discrete cell-type and differentiation state-specific DNA methylation and gene expression patterns that were maintained in a subset of breast carcinomas and correlated with clinically relevant tumor subtypes. CD44+ cells were the most hypomethylated and highly expressed several transcription factors with known stem cell function including HOXA10 and TCF3. Many of these genes were also hypomethylated in BMP4-treated compared with undifferentiated human embryonic stem (ES) cells that we analyzed by MSDK for comparison. Further highlighting the similarity of epigenetic programs of embryonic and mammary epithelial cells, genes highly expressed in CD44+ relative to more differentiated CD24+ cells were significantly enriched for Suz12 targets in ES cells. The expression of FOXC1, one of the transcription factors hypomethylated and highly expressed in CD44+ cells, induced a progenitor-like phenotype in differentiated mammary epithelial cells. These data suggest that epigenetically controlled transcription factors play a key role in regulating mammary epithelial cell phenotypes and imply similarities among epigenetic programs that define progenitor cell characteristics. C1 [Bloushtain-Qimron, Noga; Yao, Jun; Snyder, Eric L.; Shipitsin, Michail; Campbell, Lauren L.; Hua, Min; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chen, Haiyan; Gelman, Rebecca S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Yao, Jun; Snyder, Eric L.; Shipitsin, Michail; Hua, Min; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Richardson, Andrea L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Campbell, Lauren L.; Polyak, Kornelia] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chen, Haiyan] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Bloushtain-Qimron, Noga; Argani, Pedram; Porgador, Angel] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Microbiol & Immunol, IL-84105 Beer Sheva, Israel. [Bloushtain-Qimron, Noga; Argani, Pedram; Porgador, Angel] Ben Gurion Univ Negev, Canc Res Ctr, IL-84105 Beer Sheva, Israel. [Mani, Sendurai A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Ustyansky, Vadim; Nikolskaya, Tatiana; Nikolsky, Yuri] GeneGo Inc, St Joseph, MI 49085 USA. [Antosiewicz, Jessica E.; Thomson, James A.] Univ Wisconsin, Sch Med, Madison, WI 53706 USA. [Halushka, Marc K.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. [Pharoah, Paul] Can Res UK, Cambridge CB2 0RE, England. [Parsons, Ramon] Columbia Univ, Dept Med, New York, NY 10032 USA. [Stampfer, Martha R.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. [Nikolskaya, Tatiana] Russian Acad Sci, NI Vavilov Gen Genet Res Inst, Moscow 117809, Russia. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St D740C, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu RI Nikolskaya, Tatiana/M-5008-2013; Mani, Sendurai/A-7244-2009; OI Mani, Sendurai/0000-0002-5918-4276; Halushka, Marc/0000-0002-7112-7389 FU National Institutes of Health [CA89393, CA94074, CA116235, CA112970]; U.S. Department of Defense [W81XWH-07-1-0294]; American Cancer Society [RSG-05-154-01-MGO]; Susan Komen Foundation [PDF042234, PDF0707996]; Fannie E. Rippel Foundation; Harvard/Dana-Farber SPORE in Breast Cancer Developmental Research; Office of Energy Research, Office of Health and Environmental Research, U.S. Department of Energy [DE-AC03-76SF00098] FX We greatly appreciate the help of Fiona Blows with the acquisition of human tissue samples and Dyane Bailey for assistance with immunohistochemistry. We thank Dr. Honami Naora (MID Anderson Cancer Center, Houston, TX) for her generous gift of the HOXA10 antibody; the Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada, and the Cancer Genome Anatomy Project for MSDK and SAGE library sequencing, respectively. This work was supported by the National Institutes of Health Grants CA89393, CA94074, and CA116235 (to K.P.), U.S. Department of Defense Grant W81XWH-07-1-0294 (to K.P.), and American Cancer Society Grant RSG-05-154-01-MGO (to K.P.); Susan Komen Foundation fellowships PDF042234 (to M.H.) and PDF0707996 (to M.S.); Fannie E. Rippel Foundation fellowship (S.A.M.); Harvard/Dana-Farber SPORE in Breast Cancer Developmental Research (E.L.S.); and the Office of Energy Research, Office of Health and Environmental Research, U.S. Department of Energy, Contract DE-AC03-76SF00098 (to M.R.S.); and National Institutes of Health Grant CA112970 (to M.R.S.). NR 26 TC 132 Z9 139 U1 0 U2 15 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 SEP 16 PY 2008 VL 105 IS 37 BP 14076 EP 14081 DI 10.1073/pnas.0805206105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 351QG UT WOS:000259438500071 PM 18780791 ER PT J AU Cavazos, JM Naik, AD Woofter, A Abraham, NS AF Cavazos, J. M. Naik, A. D. Woofter, A. Abraham, N. S. TI Barriers to physician adherence to nonsteroidal anti-inflammatory drug guidelines: a qualitative study SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; HEART-FAILURE; MANAGEMENT; OSTEOARTHRITIS; PATIENT; HYPERTENSION; PRESCRIPTION; HEURISTICS; KNOWLEDGE; ATTITUDES AB Background Despite wide availability of physician guidelines for safer use of nonsteroidal anti-inflammatory drugs (NSAIDs) and widespread use of these drugs in the US, NSAID prescribing guidelines have been only modestly effective. Aim To identify and describe comprehensively barriers to provider adherence to NSAID prescribing guidelines. Methods We conducted interviews with 25 physicians, seeking to identify the major influences explaining physician non-adherence to guidelines. Interviews were standardized and structured probes were used for clarification and detail. All interviews were audio-taped and transcribed. Three independent investigators analysed the transcripts, using the constant-comparative method of qualitative analysis. Results Our analysis identified six dominant physician barriers explaining non-adherence to established NSAID prescribing guidelines. These included (i) lack of familiarity with guidelines, (ii) perceived limited validity of guidelines, (iii) limited applicability of guidelines among specific patients, (iv) clinical inertia, (v) influences of prior anecdotal experiences and (vi) medical heuristics. Conclusions A heterogeneous set of influences are barriers to physician adherence to NSAID prescribing guidelines. Suggested measures for improving guideline-concordant prescribing should focus on measures to improve physician education and confidence in guidelines, implementation of physician/pharmacist co-management strategies and expansion of guideline scope. C1 [Woofter, A.; Abraham, N. S.] Michael E DeBakey Vet Affairs Med ctr, Houston, TX 77030 USA. [Woofter, A.; Abraham, N. S.] Baylor Coll Med, Houston, TX 77030 USA. [Cavazos, J. M.; Naik, A. D.; Abraham, N. S.] Gastrointestinal Outcomes Geriat GO GERI Unit, Houston, TX USA. [Cavazos, J. M.; Abraham, N. S.] Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. RP Abraham, NS (reprint author), Michael E DeBakey Vet Affairs Med ctr, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM nabraham@bcm.tmc.edu FU American Gastroenterological Association Foundation-Sucampo-ASP; Department of Veterans Affairs (VA) [IIR 115-05]; NIA K23 [5K23AG027144]; Houston VA HSR&D Center of Excellence [HFP90-020] FX Declaration of personal interests: Dr Abraham guarantees the intellectual content of this paper. Each author's contribution to the paper: Dr Abraham conceived, designed and conducted the study, acquired necessary funding, interpreted the data, assisted in preparation of the manuscript and had final approval of this research. Dr Woofter conducted interviews and participated in data analysis. Dr Cavazos participated in analysis of data and preparation of the manuscript. Dr Naik participated in data analysis, interpretation and in preparation of the manuscript. Declaration of funding interests: Dr Abraham is supported by an American Gastroenterological Association Foundation-Sucampo-ASP Designated Research Award in Geriatric Gastroenterology and a Merit Review Award from the Department of Veterans Affairs (VA) (IIR 115-05). Dr Naik is supported by an NIA K23 grant (5K23AG027144). None of the funding agencies played a role in the design and conduct of the study, analysis and interpretation of the data, or the preparation and approval of the manuscript. This material is the result of work supported with resources and the use of facilities at Houston VA HSR&D Center of Excellence (HFP90-020). The views expressed herein are those of the authors and do not necessarily reflect those of the Department of Veterans Affairs (Baylor College of Medicine). NR 39 TC 22 Z9 22 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD SEP 15 PY 2008 VL 28 IS 6 BP 789 EP 798 DI 10.1111/j.1365-2036.2008.03791.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 339SD UT WOS:000258596700014 PM 19145734 ER PT J AU Tickoo, S Fonarow, GC Hernandez, AF Liang, L Cannon, CP AF Tickoo, Surnit Fonarow, Gregg C. Hernandez, Adrian F. Liang, Li Cannon, Christopher P. TI Weekend/holiday versus weekday hospital discharge and guideline adherence (from the American Heart Association's Get with the Guidelines - Coronary Artery Disease database) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; TIME; MORTALITY; WEEKEND; CARE AB Most hospitals have reduced medical staff on weekends. Furthermore, a recent study on acute myocardial infarction suggested that weekend admissions were associated with higher mortality compared with weekday admissions. We sought to determine if compliance with guideline recommendations for acute coronary syndrome performance measures would be worse on weekends/holidays compared with weekdays. We utilized the American Heart Association's Get with the Guidelines (GWTG) - Coronary Artery Disease database. This study included 154,910 patients admitted to 515 various hospitals from January 14, 2060 to April 30, 2007 with acute coronary syndrome (ACS). Patients discharged on weekdays were older and were more likely to be women, have a history of atrial fibrillation, cerebral vascular accident/transient ischemic attack and chronic renal insufficiency, and present with unstable angina. Although patients discharged on the weekends/holidays were slightly less likely to receive angiotensin-converting enzyme inhibitors than those discharged on weekdays (68.3% vs 69.5%, p < 0.0001), all other measures were similar, and a composite performance measure for 100% compliance was equal in both groups (81.5% vs 81.4%, p = 0.77). In conclusion, within GWTG participating hospitals, weekend/holiday staffing provides the same quality of care in ACS for discharge medications and counseling compared with full weekday staffing. However, there remain further opportunities to improve utilization of guideline-recommended therapies irrespective of discharge day. (C) 2008 Elsevier Inc. All rights reserved. C1 [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Tickoo, Surnit] Danbury Hosp, Div Cardiol, Danbury, CT USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Log Angeles Med Ctr, Los Angeles, CA USA. [Hernandez, Adrian F.; Liang, Li] Duke Clin Res Inst, Durham, NC USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 NR 11 TC 9 Z9 9 U1 0 U2 3 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 SEP 15 PY 2008 VL 102 IS 6 BP 663 EP 667 DI 10.1016/j.amjcard.2008.04.053 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 355DS UT WOS:000259689900004 PM 18773984 ER PT J AU Scragg, R Camargo, CA AF Scragg, Robert Camargo, Carlos A., Jr. TI Frequency of leisure-time physical activity and serum 25-hydroxyvitamin D levels in the US population: Results from the Third National Health and Nutrition Examination Survey SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aged; ethnic groups; exercise; vitamin D ID VITAMIN-D STATUS; HYPOVITAMINOSIS-D; D SUPPLEMENTATION; EXERCISE; AGE; CANCER; SKIN; DETERMINANTS; ASSOCIATION; PREVALENCE AB The decline in vitamin D status among older people is probably due to decreased synthesis of vitamin D by sun-exposed skin and/or decreased outdoor activity. The authors examined the association between outdoor leisure physical activity and serum 25-hydroxyvitamin D in the Third National Health and Nutrition Examination Survey (1988-1994) (n = 15,148 aged >= 20 years). The mean 25-hydroxyvitamin D concentration declined with increasing age, with 79, 73, and 68 nmol/liter for persons aged 20-39, 40-59, and 60 or more years. The proportion that engaged in outdoor activity in the past month was 80% for persons aged 20-39 and 40-59 years but 71% for those aged 60 or more years. In contrast, the mean difference in 25-hydroxyvitamin D between those who participated in outdoor activities daily compared with those who did not participate in the past month was similar for the youngest and oldest age groups: 13 and 16 nmol/liter, respectively. Those persons aged 60 or more years who participated in daily outdoor activities had a mean 25-hydroxyvitamin D concentration similar to that of persons aged 20-39 years: 77 versus 79 nmol/liter, respectively. These nationally representative data suggest that persons aged 60 or more years can synthesize enough vitamin D from daily outdoor activities to maintain vitamin D levels similar to those of young adults. C1 [Scragg, Robert] Univ Auckland, Sch Populat Hlth, Auckland 1142, New Zealand. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Scragg, R (reprint author), Univ Auckland, Sch Populat Hlth, Private Bag 92019, Auckland 1142, New Zealand. EM r.scragg@auckland.ac.nz OI Scragg, Robert/0000-0003-0013-2620 FU Health Research Council of New Zealand; Massachusetts General Hospital Center for D-receptor Activation Research (Boston, Massachusetts) [R01 HL84401] FX Dr. Scragg was supported by the Health Research Council of New Zealand. Dr. Camargo was supported by the Massachusetts General Hospital Center for D-receptor Activation Research (Boston, Massachusetts) and grant R01 HL84401 (Bethesda, Maryland).; The authors thank the Centers for Disease Control and Prevention (Hyattsville, Maryland) for making these data available for analysis. NR 36 TC 111 Z9 111 U1 0 U2 4 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 SEP 15 PY 2008 VL 168 IS 6 BP 577 EP 586 DI 10.1093/aje/kwn163 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 344WY UT WOS:000258959200005 PM 18579538 ER PT J AU Scragg, R Camargo, CA AF Scragg, Robert Camargo, Carlos A., Jr. TI Scragg and Camargo respond to "Physical Activity and Vitamin D" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID 25-HYDROXYVITAMIN-D C1 [Scragg, Robert] Univ Auckland, Sch Populat Hlth, Auckland 1142, New Zealand. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Scragg, R (reprint author), Univ Auckland, Sch Populat Hlth, Private Bag 92019, Auckland 1142, New Zealand. EM r.scragg@auckland.ac.nz OI Scragg, Robert/0000-0003-0013-2620 NR 5 TC 1 Z9 1 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 SEP 15 PY 2008 VL 168 IS 6 BP 590 EP 591 DI 10.1093/aje/kwn166 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 344WY UT WOS:000258959200007 ER PT J AU Liu, KD Levitt, J Zhuo, HJ Kallet, RH Brady, S Steingrub, J Tidswell, M Siegel, MD Soto, G Peterson, MW Chesnutt, MS Phillips, C Weinacker, A Thompson, BT Eisner, MD Matthay, MA AF Liu, Kathleen D. Levitt, Joseph Zhuo, Hanjing Kallet, Richard H. Brady, Sandra Steingrub, Jay Tidswell, Mark Siegel, Mark D. Soto, Graciela Peterson, Michael W. Chesnutt, Mark S. Phillips, Charles Weinacker, Ann Thompson, B. Taylor Eisner, Mark D. Matthay, Michael A. TI Randomized clinical trial of activated protein C for the treatment of acute lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; acute lung injury; activated protein C; ventilator-free days; mortality ID RESPIRATORY-DISTRESS-SYNDROME; SEVERE SEPSIS; SEPTIC SHOCK; ARDS; OUTCOMES; FLUID AB Rationale: Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days. Objectives: To test the efficacy of activated protein C (APC) as a therapy for patients with ALI. Methods: Eligible subjects were critically ill patients who met the American/European consensus criteria for ALI. Patients with severe sepsis and an APACHE 11 score of 25 or more were excluded. Participants were randomized to receive APC (24 mu g/kg/h for 96 h) or placebo in a double-blind fashion within 72 hours of the onset of ALI. The primary endpoint was ventilator-free days. Measurements and Main Results: APC increased plasma protein C levels (P = 0.002) and decreased pulmonary dead space fraction (P = 0.02). However, there was no statistically significant difference between patients receiving placebo (n = 38) or APC (n = 37) in the number of ventilator-free days (median [25-75% interquartile range]: 19 [0-24] vs. 19 [14-22], respectively; P = 0.78) or in 60-day mortality (5/38 vs. 5/37 patients, respectively; P = 1.0). There were no differences in the number of bleeding events between the two groups. Conclusions: APC did not improve outcomes from ALI. The results of this trial do not support a large clinical trial of APC for ALI in the absence of severe sepsis and high disease severity. C1 [Liu, Kathleen D.] Univ Calif San Francisco, Dept Med, Div Nephrol & Crit Care Med, San Francisco, CA 94143 USA. [Levitt, Joseph; Weinacker, Ann] Stanford Univ, Div Pulm & Crit Care Med, Stanford, CA 94305 USA. [Zhuo, Hanjing; Kallet, Richard H.; Brady, Sandra] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Steingrub, Jay; Tidswell, Mark] Baystate Med Ctr, Div Pulm & Crit Care Med, Springfield, MA USA. [Siegel, Mark D.] Yale Univ, Pulm & Crit Care Sect, New Haven, CT USA. [Soto, Graciela] Univ So Calif, Div Pulm & Crit Care Med, Los Angeles, CA USA. [Peterson, Michael W.] UCSF Fresno, Div Pulm & Crit Care Med, Fresno, CA USA. [Chesnutt, Mark S.; Phillips, Charles] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Eisner, Mark D.] Univ Calif San Francisco, Dept Med, Div Occupat Med, San Francisco, CA 94143 USA. [Matthay, Michael A.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. RP Liu, KD (reprint author), Univ Calif San Francisco, Dept Med, Div Nephrol & Crit Care Med, Box 0532, San Francisco, CA 94143 USA. EM kathleen.liu@ucsf.edu FU NCRR NIH HHS [8 K12 RR023262]; NHLBI NIH HHS [HL74005] NR 27 TC 109 Z9 112 U1 0 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 15 PY 2008 VL 178 IS 6 BP 618 EP 623 DI 10.1164/rccm.200803-419OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 347RL UT WOS:000259158600011 PM 18565951 ER PT J AU Gordin, FM Roediger, MP Girard, PM Lundgren, JD Miro, JM Palfreeman, A Rodriguez-Barradas, MC Wolff, MJ Easterbrook, PJ Clezy, K Slater, LN AF Gordin, Fred M. Roediger, Mollie P. Girard, Pierre-Marie Lundgren, Jens D. Miro, Jose M. Palfreeman, Adrian Rodriguez-Barradas, Maria C. Wolff, Marcelo J. Easterbrook, Philippa J. Clezy, Kate Slater, Leonard N. TI Pneumonia in HIV-infected persons - Increased risk with cigarette smoking and treatment interruption SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE pneumonia; smoking; HIV; bacterial infections ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; INVASIVE PNEUMOCOCCAL DISEASE; COMMUNITY-ACQUIRED PNEUMONIA; BACTERIAL PNEUMONIA; PULMONARY COMPLICATIONS; POLYSACCHARIDE VACCINE; DRUG-USERS; COHORT; ADULTS AB Rationale: Bacterial pneumonia is a major cause of morbidity for HIV-infected persons and contributes to excess mortality in this population. Objectives: To evaluate the frequency and risk factors for occurrence of bacterial pneumonia in the present era of potent antiretroviral therapy. Methods: We evaluated data from a randomized trial of episodic antiretroviral therapy. The study, Strategies for Management of Antiretroviral Therapy, enrolled 5,472 participants at 318 sites in 33 countries. Study patients had more than 350 CD4 cells at baseline. Diagnosis of bacterial pneumonia was confirmed by a blinded clinical-events committee. Measurements and Main Results: During a mean follow-up of 16 months, 116 participants (2.2%) developed at least one episode of bacterial pneumonia. Patients randomized to receive episodic antiretroviral therapy were significantly more likely to develop pneumonia than patients randomized to receive continuous antiretroviral therapy (hazard ratio, 1.55; 95% confidence interval, 1.07-2.25; P = 0.02). Cigarette smoking was a major risk factor: Current-smokers had more than an 80% higher risk of pneumonia compared with never-smokers (hazard ratio, 1.82; 95% confidence interval, 1.09-3.04; P = 0.02). Participants who were on continuous HIV treatment and were current smokers were three times more likely to develop bacterial pneumonia than nonsmokers. Current smoking status was significant, but a past history of smoking was not. Conclusions: Bacterial pneumonia is a major source of morbidity, even for persons on potent antiretroviral therapy, including those with high CD4 cells. Efforts to reduce this illness should stress the importance of uninterrupted antiretroviral therapy and attainment and/or maintenance of nonsmoking status. C1 [Gordin, Fred M.] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Gordin, Fred M.] George Washington Univ, Washington, DC USA. [Roediger, Mollie P.] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Girard, Pierre-Marie] Univ Paris 06, Hop St Antoine, Serv Malad Infect & Trop, Paris, France. [Girard, Pierre-Marie] Inst Med & Epidemiol Appl, Paris, France. [Lundgren, Jens D.] Univ Copenhagen, Copenhagen HIV Programme, Copenhagen, Denmark. [Miro, Jose M.] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi Sunyer, Barcelona, Spain. [Palfreeman, Adrian] Univ Hosp, Leicester, Leics, England. [Palfreeman, Adrian] MRC, London, England. [Rodriguez-Barradas, Maria C.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA. [Wolff, Marcelo J.] Univ Chile, Sch Med, Santiago, Chile. [Wolff, Marcelo J.] Arriaran Fdn, Santiago, Chile. [Easterbrook, Philippa J.] Kings Coll London, Dept HIV & Genitourinary Med, London WC2R 2LS, England. [Clezy, Kate] Univ New S Wales, Sydney, NSW, Australia. [Slater, Leonard N.] Univ Oklahoma, Coll Med, Oklahoma City, OK 73190 USA. [Slater, Leonard N.] Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA. RP Gordin, FM (reprint author), Vet Affairs Med Ctr, 151B,50 Irving St NW, Washington, DC 20422 USA. EM fred.gordin@med.va.gov OI Lundgren, Jens/0000-0001-8901-7850 FU Medical Research Council [G0200585, MC_U122886352]; NIAID NIH HHS [U01AI042170, U01AI46362] NR 28 TC 52 Z9 55 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 15 PY 2008 VL 178 IS 6 BP 630 EP 636 DI 10.1164/rccm.200804-617OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 347RL UT WOS:000259158600013 PM 18617640 ER PT J AU Contreras, MA Haq, E Uto, T Singh, I Singh, AK AF Contreras, Miguel Agustin Haq, Ehtishamul Uto, Takuhiro Singh, Inderjit Singh, Avtar Kaur TI Psychosine-induced alterations in peroxisomes of twitcher mouse liver SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE TNF-alpha; IL-6; neuroinflammation; Krabbe disease; twitcher mouse; peroxisomes; psychosine; sphingolipid; catalase; liver ID GLOBOID-CELL LEUKODYSTROPHY; TANDEM MASS-SPECTROMETRY; BETA-OXIDATION ENZYMES; NECROSIS-FACTOR-ALPHA; C6 GLIAL-CELLS; RAT-LIVER; TNF-ALPHA; BRAIN; EXPRESSION; DISEASE AB Krabbe disease is a neuroinflammatory disorder in which galactosylsphingosine (psychosine) accumulates in nervous tissue. To gain insight into whether the psychosine-induced effects in nervous tissue extend to peripheral organs, we investigated the expression of cytokines and their effects on peroxisomal structure/functions in twitcher mouse liver (animal model of Krabbe disease). Immunofluorescence analysis demonstrated TNF-alpha and IL-6 expression, which was confirmed by mRNAs quantitation. Despite the presence of TNF-alpha, lipidomic analysis did not indicate a significant decrease in sphingomyelin or an increase in ceramide fractions. Ultrastructural analysis of catalase-dependent staining of liver sections showed reduced reactivity without significant changes in peroxisomal contents. This observation was confirmed by assaying catalase activity and quantitation of its mRNA, both of which were found significantly decreased in twitcher mouse liver. Western blot analysis demonstrated a generalized reduction of peroxisomal matrix and membrane proteins. These observations indicate that twitcher mouse pathobiology extends to the liver, where psychosine-incluced TNF-alpha and IL-6 compromise peroxisomal structure and functions. (C) 2008 Published by Elsevier Inc. C1 [Singh, Avtar Kaur] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Singh, Avtar Kaur] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29425 USA. [Contreras, Miguel Agustin; Haq, Ehtishamul; Uto, Takuhiro; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Contreras, Miguel Agustin; Haq, Ehtishamul; Uto, Takuhiro; Singh, Inderjit] Med Univ S Carolina, Charles Darby Childrens Res Inst, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. EM avtar.singh@med.va.gov OI Haq, Ehtishamul/0000-0002-4195-0606 FU National Center for Research Resources [C06 RR018823, C06 RR015455]; National Institutes of Health [NS-22576, NS-34741, NS-37766, NS-40810, AG-25307] FX The authors would like to thank Ms. Joyce Bryan, Mrs. Rifat Yasmeen, Mrs. Carol Moskos, Mrs. Carrie Barnes (R.H. Johnson Veteran's Administration Medical Center), and Dr. Jacek Bielawsky and Mr. Jason Pierce (Lipidomics Core Facility) for excellent technical assistance; and Drs. Ernest Barbosa, Ravinder Pannu and Mushfiquddin Khan for helpful discussions and scientific advice. This work was supported by Grants from the Extramural Research Facilities Program of the National Center for Research Resources (C06 RR018823 and C06 RR015455) and from the National Institutes of Health (NS-22576, NS-34741, NS-37766, NS-40810 and AG-25307). NR 57 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 15 PY 2008 VL 477 IS 2 BP 211 EP 218 DI 10.1016/j.abb.2008.06.012 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 347VR UT WOS:000259170000004 PM 18602885 ER PT J AU Castelino, FV Wasfy, JH Collier, D AF Castelino, Flavia V. Wasfy, Jason H. Collier, Deborah TI A 36-year-old man with paresthesias and a headache SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID HEPATITIS-B-VIRUS; NON-HODGKINS-LYMPHOMA; POLYARTERITIS-NODOSA; PERIPHERAL NEUROPATHY; AUSTRALIA ANTIGEN; PLASMA-EXCHANGE; MANIFESTATIONS; INFECTION; COCAINE; SUPERIORITY C1 [Castelino, Flavia V.] Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA. RP Castelino, FV (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2C-2100,55 Fruit St, Boston, MA 02114 USA. EM fcastelino@partners.org NR 31 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD SEP 15 PY 2008 VL 59 IS 9 BP 1358 EP 1365 DI 10.1002/art.24008 PG 8 WC Rheumatology SC Rheumatology GA 354WI UT WOS:000259669700019 PM 18759310 ER PT J AU Shields, DC Asaad, W Eskandar, EN Jain, FA Cosgrove, GR Flaherty, AW Cassern, EH Price, BH Rauch, SL Dougherty, DD AF Shields, Donald C. Asaad, Wael Eskandar, Ernad N. Jain, Felipe A. Cosgrove, G. Rees Flaherty, Alice W. Cassern, Edwin H. Price, Bruce H. Rauch, Scott L. Dougherty, Darin D. TI Prospective assessment of stereotactic ablative surgery for intractable major depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anterior cingulotomy; limbic leucotomy; major depression; microelectrode recording; stereotactic ablation; subcaudate tractotomy ID OBSESSIVE-COMPULSIVE DISORDER; TERM FOLLOW-UP; FRONTAL-LOBE; FUNCTIONAL NEUROANATOMY; RESISTANT DEPRESSION; MOOD DISORDERS; PSYCHOSURGERY; CINGULOTOMY; HYPOMETABOLISM; CIRCUITS AB Background: Despite therapeutic advances for major depression, a subset of patients with this disorder does not respond to conventional treatment. Stereotactic ablative procedures such as anterior cingulotomy have been performed in severely affected, treatment-resistant patients, but the long-term results of such procedures are not fully understood. Methods: Findings are reported for 33 patients with severe treatment-resistant major depression who underwent ablative stereotactic procedures (dorsal anterior cingulotomy followed if necessary by subcaudate tractotomy). Preoperative and long-term postoperative Beck Depression Inventory scores were obtained along with postoperative Clinical Global Improvement values. Both were analyzed to evaluate patients' responses to the surgical procedure(s). Results: At mean follow-up of 30 months after one or more stereotactic ablative procedures, I I patients (33.3%) were classified as responders, 14 (42.4%) were partial responders, and 8 (24.2%) did not respond to the surgical procedure(s). Among those (17) who underwent only one procedure, seven (41.2%) responded, whereas six (35.3%) and four (23.5%) showed partial or no response, respectively. Among patients who required multiple surgical procedures, four patients (25%) responded, whereas eight (50%) and four (25%) patients demonstrated partial or no responses, respectively, at long-term follow-up evaluations. Conclusions: Approximately 75% of depression patients previously resistant to antidepressant therapies received partial or substantial benefit from stereotactic ablative procedures. Those requiring only a single anterior cingulotomy tended to demonstrate more pronounced responses than patients who underwent multiple surgical procedures. C1 [Shields, Donald C.; Asaad, Wael; Eskandar, Ernad N.; Cosgrove, G. Rees] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Flaherty, Alice W.; Price, Bruce H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Jain, Felipe A.; Cassern, Edwin H.; Rauch, Scott L.; Dougherty, Darin D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St, Charlestown, MA 02129 USA. EM ddougherty@partners.org RI Asaad, Wael/I-8485-2012 OI Asaad, Wael/0000-0003-4406-9096 FU sydney R. Baer Jr. Foundation FX The work, of Bruce H. Price, M.D. is supported in part by the sydney R. Baer Jr. Foundation. We wish to thank Valerie Giorgione and Mariko Jameson for their contributions to this study.; Drs. Shields, Asaad, Eskandar Jain, Cosgrove, Flaherty, Cassem, Price, and Rauch reported no biomedical financial interests or potential conflicts of interest. Dr. Dougherty discloses, support/ honoraria from Cyberonics and McNeil and research support from Medtronic, Northstar Neuroscience, Pfizer, Eli Lilly, Forest, and Cepbalon. NR 25 TC 27 Z9 27 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2008 VL 64 IS 6 BP 449 EP 454 DI 10.1016/j.biopsych.2008.04.009 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 343YJ UT WOS:000258892000002 PM 18486107 ER PT J AU Nierenberg, AA Alpert, JE Gardner-Schuster, EE Seay, S Mischoulon, D AF Nierenberg, Andrew A. Alpert, Jonathan E. Gardner-Schuster, Erica E. Seay, Sheila Mischoulon, David TI Vagus nerve stimulation: 2-year outcomes for bipolar versus unipolar treatment-resistant depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE 2-year outcome; bipolar treatment-resistant depression; vagus nerve stimulation ID DISORDER AB Background: The outcome of vagus nerve stimulation (VNS) for patients with bipolar treatment-resistant depression (TRD) has not been well characterized. This study describes the outcome of VNS for bipolar TRD patients participating in the acute and longitudinal pivotal trials and compares their outcome with unipolar TRID patients in the same trials. Methods: Of 235 participants enrolled in the acute study, 25 (11%) were diagnosed with DSM-IV bipolar I or 11 disorder. A sham-controlled 12-week trial of VNS preceded 2 years of open treatment. Bipolar and unipolar subjects were compared on baseline characteristics as well as acute and long-term outcomes. Results: At baseline, bipolar TRD was as severe as unipolar TRID but with depressive episodes of shorter duration and more failed antidepressant trials/year. Acute, 1-year, and 2-year outcomes were similar for both groups, even when the definition of response for bipolar TRD was expanded to include lack of manic symptoms. Conclusions: Bipolar TRID is a serious condition. In this hypothesis-generating analysis, VNS short- and long-term effects on bipolar and unipolar TRD were similar. Because these analyses were post hoc, these findings should not be interpreted as warranting clinical inference regarding effectiveness of VNS in patients with bipolar depression. C1 [Nierenberg, Andrew A.; Alpert, Jonathan E.; Gardner-Schuster, Erica E.; Mischoulon, David] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Seay, Sheila] Cyberonics, Houston, TX USA. RP Nierenberg, AA (reprint author), 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM anierenberg@partners.org OI Alpert, Jonathan/0000-0002-4332-908X NR 8 TC 41 Z9 42 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2008 VL 64 IS 6 BP 455 EP 460 DI 10.1016/j.biopsych.2008.04.036 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 343YJ UT WOS:000258892000003 PM 18571625 ER PT J AU Berk, M Copolov, DL Dean, O Lu, K Jeavons, S Schapkaitz, I Anderson-Hunt, M Bush, AI AF Berk, Michael Copolov, David L. Dean, Olivia Lu, Kristy Jeavons, Sue Schapkaitz, Ian Anderson-Hunt, Murray Bush, Ashley I. TI N-acetyl cysteine for depressive symptoms in bipolar disorder - A double-blind randomized placebo-controlled trial SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; clinical trial; depression; glutathione; N-acetyl cysteine; neurochemistry ID OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; GLUTATHIONE DEFICIT; ANTIOXIDANT ENZYMES; CEREBROSPINAL-FLUID; LIPID-PEROXIDATION; GENE-EXPRESSION; CLINICAL-TRIALS; IN-VIVO; ACETYLCYSTEINE AB Background: Treatment-resistant subthreshold depression is a major problem in bipolar disorder. Both depression and bipolar disorder are complicated by glutathione depletion. We hypothesized that treatment with N-acetyl cysteine (NAC), a safe, orally bioavailable precursor of glutathione, may improve the depressive component of bipolar disorder. Methods: A randomized, double-blind, multicenter, placebo-controlled study of individuals (n = 75) with bipolar disorder in the maintenance phase treated with NAC (I g twice daily) adjunctive to usual medication over 24 weeks, with a 4-week washout. The two primary outcomes were the Montgomery Asberg Depression Rating Scale (MADRS) and time to a mood episode. Secondary outcomes included the Bipolar Depression Rating Scale and 11 other ratings of clinical status, quality of life, and functioning. Results: NAC treatment caused a significant improvement on the MANS (least squares mean difference [95% confidence interval]: -8.05 [-13.16, -2.95], p =.002) and most secondary scales at end point. Benefit was evident by 8 weeks on the Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale and at 20 weeks on the MADRS. Improvements were lost after washout. There was no effect of NAC on time to a mood episode (log-rank test: p =.968) and no significant between-group differences in adverse events. Effect sizes at end point were medium to high for improvements in MADRS and 9 of the 12 secondary readouts. Conclusions: NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar disorder. C1 [Berk, Michael; Copolov, David L.; Dean, Olivia; Bush, Ashley I.] Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. [Berk, Michael; Lu, Kristy; Schapkaitz, Ian; Anderson-Hunt, Murray] Univ Melbourne, Dept Clin & Biomed Sci, Geelong, Vic, Australia. [Berk, Michael] Orygen Youth Hlth, Melbourne, Vic, Australia. [Copolov, David L.] Monash Univ, Clayton, Vic, Australia. [Jeavons, Sue] Bendigo Hlth, Bendigo, Australia. [Bush, Ashley I.] Univ Melbourne, Dept Pathol, Geelong, Vic, Australia. [Bush, Ashley I.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Bush, AI (reprint author), Mental Hlth Res Inst Victoria, 155 Oak St, Parkville, Vic 3052, Australia. EM bush@helix.mgh.harvard.edu RI Berk, Michael/M-7891-2013; Bush, Ashley/A-1186-2007 OI Berk, Michael/0000-0002-5554-6946; Bush, Ashley/0000-0001-8259-9069 FU Stanley Medical Research, Institute; The Mental Health Research Institute of Victoria; Australian Research Council Federation; Commonwealth Scientific and Industrial Research Organization; Woods Family Foundation; National Health and Medical Research Council of Australia FX This trial was supported by a grant from the Stanley Medical Research, Institute, as well as The Mental Health Research Institute of Victoria. AIB is supported by the Australian Research Council Federation Fellowship and The Commonwealth Scientific and Industrial Research Organization Flagship Fellowship. The Woods Family Foundation and The National Health and Medical Research Council of Australia supported OD. NR 40 TC 232 Z9 241 U1 0 U2 12 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 SEP 15 PY 2008 VL 64 IS 6 BP 468 EP 475 DI 10.1016/j.biopsych.2008.04.022 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 343YJ UT WOS:000258892000005 PM 18534556 ER PT J AU Law, RJ Munson, K Sachs, G Lightstone, FC AF Law, Richard J. Munson, Keith Sachs, George Lightstone, Felice C. TI An ion gating mechanism of gastric H,K-ATPase based on molecular dynamics simulations SO BIOPHYSICAL JOURNAL LA English DT Article ID SARCOPLASMIC-RETICULUM; BINDING-SITES; CALCIUM-PUMP; TRANSMEMBRANE SEGMENT; POTASSIUM CHANNEL; CRYSTAL-STRUCTURE; ALPHA-SUBUNIT; K+; NA,K-ATPASE; WATER AB Gastric H, K-ATPase is an electroneutral transmembrane pump that moves protons from the cytoplasm of the parietal cell into the gastric lumen in exchange for potassium ions. The mechanism of transport against the established electrochemical gradients includes intermediate conformations in which the transferred ions are trapped (occluded) within the membrane domain of the pump. The pump cycle involves switching between the E1 and E2P states. Molecular dynamics simulations on homology models of the E2P and E1 states were performed to investigate the mechanism of K+ movement in this enzyme. We performed separate E2P simulations with one K+ in the luminal channel, one K+ ion in the occlusion site, two K+ ions in the occlusion site, and targeted molecular dynamics from E2P to E1 with two K+ ions in the occlusion site. The models were inserted into a lipid bilayer system and were stable over the time course of the simulations, and K+ ions in the channel moved to a consistent location near the center of the membrane domain, thus de. ning the occlusion site. The backbone carbonyl oxygen from residues 337 through 342 on the nonhelical turn of M4, as well as side-chain oxygen from E343, E795, and E820, participated in the ion occlusion. A single water molecule was stably bound between the two K+ ions in the occlusion site, providing an additional ligand and partial shielding the positive charges from one another. Targeted molecular dynamics was used to transform the protein from the E2P to the E1 state (two K+ ions to the cytoplasm). This simulation identified the separation of the water column in the entry channel as the likely gating mechanism on the luminal side. A hydrated exit channel also formed on the cytoplasmic side of the occlusion site during this simulation. Hence, water molecules became available to hydrate the ions. The movement of the M1M2 transmembrane segments, and the displacement of residues Q159, E160, Q110, and T152 during the conformational change, as well as the motions of E343 and L346, acted as the cytoplasmic-side gate. C1 [Law, Richard J.; Lightstone, Felice C.] Lawrence Livermore Natl Lab, Chem Mat Earth & Life Sci Directorate, Livermore, CA 94550 USA. [Munson, Keith; Sachs, George] Univ Calif Los Angeles, David Geffen Sch Med, Lab Membrane Biol, Los Angeles, CA 90024 USA. [Munson, Keith; Sachs, George] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. RP Lightstone, FC (reprint author), Lawrence Livermore Natl Lab, Chem Mat Earth & Life Sci Directorate, L-372,700 E Ave, Livermore, CA 94550 USA. EM felice@llnl.gov FU National Institutes of Health [DK058333]; U. S. Department of Energy by the Lawrence Livermore National Laboratory [DE-AC52-07NA27344]; Laboratory Directed Research and Development Program at the Lawrence Livermore National Laboratory [UCRL-JRNL-2333318] FX The work of K. M and G. S. is supported by the National Institutes of Health grant DK058333. This work was performed under the auspices of the U. S. Department of Energy by the Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. The project 06-SI-003 was funded by the Laboratory Directed Research and Development Program at the Lawrence Livermore National Laboratory, UCRL-JRNL-2333318. NR 37 TC 10 Z9 10 U1 0 U2 2 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP 15 PY 2008 VL 95 IS 6 BP 2739 EP 2749 DI 10.1529/biophysj.107.128025 PG 11 WC Biophysics SC Biophysics GA 343BI UT WOS:000258826900014 PM 18567633 ER PT J AU Levine, RL Gilliland, DG AF Levine, Ross L. Gilliland, D. Gary TI Myeloproliferative disorders SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ERYTHROID COLONY FORMATION; CHROMOSOME 20Q DELETIONS; CHRONIC MYELOID-LEUKEMIA; JAK2 EXON-12 MUTATIONS; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; ACTIVATING MUTATION; MYELODYSPLASTIC-SYNDROMES AB In 1951 William Dameshek classified polycythemia vera (PV), essential thombocytosis (ET), and primary myelofibrosis (PMF) as pathogenetically related myeloproliferative disorders (MPD). Subsequent studies demonstrated that PV, ET, and PMF are clonal disorders of multipotent hematopoietic progenitors. In 2005, a somatic activating mutation in the JAK2 nonreceptor tyrosine kinase (JAK2V617F) was identified in most patients with PV and in a significant proportion of patients with ET and PMF. Subsequent studies identified additional mutations in the JAK-STAT pathway in some patients with JAK2V617F-MPD, suggesting that constitutive activation of this signaling pathway is a unifying feature of these disorders. Although the discovery of mutations in the JAK-STAT pathway is important from a pathogenetic and diagnostic perspective, important questions remain regarding the role of this single disease allele in 3 related but clinically distinct disorders, and the role of additional genetic events in MPD disease pathogenesis. In addition, these observations provide a foundation for development of small molecule inhibitors of JAK2 that are currently being tested in clinical trials. This review will discuss our understanding of the pathogenesis of PV, ET, and PMF, the potential role of JAK2-targeted therapy, and the important unanswered questions that need to be addressed to improve clinical outcome. C1 [Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Gilliland, D. Gary] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Gilliland, D. Gary] Broad Inst Harvard, Boston, MA USA. [Gilliland, D. Gary] MIT, Boston, MA USA. RP Levine, RL (reprint author), Mem Sloan Kettering Canc Ctr, Leukemia Serv, Human Oncol & Pathogenesis Program, 1275 York Ave,Box 20, New York, NY 10065 USA. EM leviner@mskcc.org; ggilliland@rics.bwh.harvard.edu FU U. S. National Institutes of Health (Bethesda, MD); Howard Hughes Medical Institute (Boston, MA); Leukemia & Lymphoma Society (White Plains, NY); Doris Duke Charitable Foundation (New York, NY); Myeloproliferative Disorders Foundation (Chicago, IL); Howard Hughes Medical Institute; Doris Duke Charitable Foundation; American Society of Hematology (Washington, DC) FX We thank the patients, physicians, and investigators who have contributed to our understanding of these disorders, and apologize to our colleagues whose work was not highlighted due to space constraints. The Gilliland Laboratory is supported by the U. S. National Institutes of Health (Bethesda, MD), the Howard Hughes Medical Institute (Boston, MA), the Leukemia & Lymphoma Society (White Plains, NY), the Doris Duke Charitable Foundation (New York, NY), and the Myeloproliferative Disorders Foundation (Chicago, IL). D. G. G. is an Investigator of the Howard Hughes Medical Institute, and a Doris Duke Charitable Foundation Distinguished Clinical Scientist Award recipient. R. L. L. is an American Society of Hematology (Washington, DC) Basic Research Fellow Award recipient, a Doris Duke Charitable Foundation Clinical Scientist Development Award recipient, a Howard Hughes Medical Institute Early Career Award recipient, and is the Geoffrey Beene Junior Chair at Memorial Sloan-Kettering Cancer Center. NR 99 TC 175 Z9 186 U1 0 U2 9 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 SEP 15 PY 2008 VL 112 IS 6 BP 2190 EP 2198 DI 10.1182/blood-2008-03-077966 PG 9 WC Hematology SC Hematology GA 346RX UT WOS:000259088000012 PM 18779404 ER PT J AU Davies, JK Gribben, JG Brennan, LL Yuk, DG Nadler, LM Guinan, EC AF Davies, Jeff K. Gribben, John G. Brennan, Lisa L. Yuk, Dongin Nadler, Lee M. Guinan, Eva C. TI Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; CORD BLOOD TRANSPLANTATION; ALLOREACTIVE T-CELLS; IMMUNE RECONSTITUTION; ACUTE-LEUKEMIA; LYMPHOPROLIFERATIVE DISORDERS; ADULT PATIENTS; HIGH-RISK; DEPLETION AB We report the outcomes of 24 patients with high-risk hematologic malignancies or bone marrow failure (BMF) who received haploidentical bone marrow transplantation (BMT) after ex vivo induction of alloantigen-specific anergy in donor T cells by allostimulation in the presence of costimulatory blockade. Ninety-five percent of evaluable patients engrafted and achieved full donor chimerism. Despite receiving a median T-cell dose of 29 x 106/kg, only 5 of 21 evaluable patients developed grade C (n = 4) or D (n = 1) acute graft-versus- host disease (GVHD), with only one attributable death. Twelve patients died from treatment-related mortality (TRM). Patients reconstituted T-cell subsets and immunoglobulin levels rapidly with evidence of in vivo expansion of pathogen-specific T cells in the early post-transplantation period. Five patients reactivated cytomegalovirus (CMV), only one of whom required extended antiviral treatment. No deaths were attributable to CMV or other viral infections. Only 1 of 12 evaluable patients developed chronic GVHD. Eight patients survive disease-free with normal performance scores (median follow-up, 7 years). Thus, despite significant early TRM, ex vivo alloanergization can support administration of large numbers of haploidentical donor T cells, resulting in rapid immune reconstitution with very few viral infections. Surviving patients have excellent performance status and a low rate of chronic GVHD. C1 [Guinan, Eva C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Ctr Clin & Translat Res, Boston, MA 02115 USA. [Davies, Jeff K.; Yuk, Dongin; Nadler, Lee M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Davies, Jeff K.; Nadler, Lee M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Gribben, John G.] St Bartholomews Hosp, Dept Med Oncol, London, England. [Guinan, Eva C.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Guinan, EC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Ctr Clin & Translat Res, 44 Binney St, Boston, MA 02115 USA. EM eva_guinan@dfci.harvard.edu FU National Institutes of Health (Bethesda, MD) [P01 AI41584, P50 HL54785]; Frank J. Hanna Jr Fund (Dana-Farber Cancer Institute, Boston, MA); Leukemia & Lymphoma Society (White Plains, NY) FX The authors thank the hospital staff who provided exceptional medical care and especially the patients and families who chose to participate in the studies.; These studies were supported by grants from the National Institutes of Health (Bethesda, MD; P01 AI41584 and P50 HL54785) and the Frank J. Hanna Jr Fund (Dana-Farber Cancer Institute, Boston, MA). J. K. D. is a recipient of a Career Development Award from the Leukemia & Lymphoma Society (White Plains, NY). NR 50 TC 43 Z9 46 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2008 VL 112 IS 6 BP 2232 EP 2241 DI 10.1182/blood-2008-03-143636 PG 10 WC Hematology SC Hematology GA 346RX UT WOS:000259088000017 PM 18617635 ER PT J AU Hatoum, HT Lin, SJ Smith, MR Barghout, V Lipton, A AF Hatoum, Hind T. Lin, Swu-Jane Smith, Mathew R. Barghout, Victoria Lipton, Allan TI Zoledronic acid and skeletal complications in patients with solid tumors and bone metastases - Analysis of a national medical claims database SO CANCER LA English DT Article DE zoledronic acid; skeletal complications; retrospective claims analysis; persistency; bone; cancer ID PLACEBO-CONTROLLED TRIAL; BREAST-CANCER; LUNG-CANCER; CARCINOMA; WOMEN; COST AB BACKGROUND. Bone is among the most con In ion sites of metastasis in patients with advanced cancer, and the development of bone metastases places patients at increased risk for skeletal complications. METHODS. This retrospective claims analysis included only patients with a diagnosis of bone metastasis who had a single type of solid turner of the breast (women), prostate, or lung and experienced >= 1 skeletal complication between January 2002 and October 2005. RESULTS. The mean follow-up (+/- standard deviation) for zoledronic acid (ZA)-treated patients versus untreated patients was 12.2 +/- 9.05 months versus 8.7 +/- 9.28 months, respectively (P < .001). The monthly rate of skeletal complications in ZA-treated patients versus untreated patients was 0.29 +/- 0.3 per month versus 0.43 +/- 0.4 per month, respectively (P <.001). Persistent ZA use was associated with longer follow-up duration (P <.05) and a greater probability of continuing follow-up. Greater persistency was associated with lower monthly rates of skeletal complications (P <.05). The length of follow-tip for ZA use according to the recommended closing schedule was 17.11 months compared with 9.93 months for nonrecommended schedules and 8.68 months for no treatment (analysis of variance; P <.001). The rate of skeletal complications with ZA use on the recommended schedule was 0.16 events per month versus 0.31 events per month for nonrecommended schedules and 0.43 events per month for no treatment. In the subgroup analysis, the mean time to first complication was 185 +/- 210 days in the GA-treated group versus 98 +/- 161 days in the untreated group (P <.0001). the mean time from the first complication to the second complication was 111 +/- 124 days in the ZA-treated group versus 86 +/- 114 days in the untreated group (P <.05). CONCLUSIONS. Real-world evidence indicated that ZA reduced the skeletal morbidity rate and delayed the time to skeletal complications. C1 [Hatoum, Hind T.; Lin, Swu-Jane] Univ Illinois, Hind T Hatoum & Co, Chicago, IL 60647 USA. [Hatoum, Hind T.; Lin, Swu-Jane] Univ Illinois, Dept Pharm Adm, Chicago, IL USA. [Smith, Mathew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Barghout, Victoria] Nova Pharmaceut Corp, Outcomes Res Oncol, Flortham Pk, NJ USA. [Lipton, Allan] Milton S Hershey Med Ctr, Div Oncol, Hershey, PA USA. RP Hatoum, HT (reprint author), Univ Illinois, Hind T Hatoum & Co, 1758 N Wilmot Ave, Chicago, IL 60647 USA. EM hthatoum@sbcglobal.net FU Novartis Pharmaceuticals FX This study was supported by Novartis Pharmaceuticals. NR 15 TC 58 Z9 60 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 2008 VL 113 IS 6 BP 1438 EP 1445 DI 10.1002/cncr.23775 PG 8 WC Oncology SC Oncology GA 346YP UT WOS:000259105800023 PM 18720527 ER PT J AU Holmes, KA Song, JS Liu, XLS Brown, M Carroll, JS AF Holmes, Kelly A. Song, Jun S. Liu, Xiaole S. Brown, Myles Carroll, Jason S. TI Nkx3-1 and LEF-1 function as transcriptional inhibitors of estrogen receptor activity SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; BINDING-SITES; CYCLIN D1; REGULATED TRANSCRIPTION; PROSTATE-CANCER; GENE-EXPRESSION; C-MYC; ACTIVATION; REVEALS; GROWTH AB Estrogen receptor (ER)-associated cofactors and cooperating transcription factors are one of the primary components determining transcriptional activity of estrogen target genes and may constitute potential therapeutic targets. Recent mapping of ER-binding sites on a genome-wide scale has provided insight into novel cooperating factors based on the enrichment of transcription factor motifs within the ER-binding sites. We have used the ER-binding sites in combination with sequence conservation to identify the statistic. enrichment of Nkx and LEF motifs. We find that Nkx3-1 a LEF-1 bind to several ER cis-regulatory elements in vivo, but they both function as transcriptional repressors of estrogen signaling. We show that Nkx3-1 and LEF-1 can inhibit ER binding to chromatin, suggesting competition for common chromatin-binding regions. These data provide insight into the role of Nkx3-1 and LEF-1 as potential regulators of the hormone response in breast cancer. C1 [Carroll, Jason S.] Canc Res UK, Cambridge Res Inst, Li Ku Shing Ctr, Cambridge CB2 0RE, England. [Song, Jun S.; Liu, Xiaole S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Brown, Myles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Song, Jun S.; Liu, Xiaole S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Song, Jun S.] Inst Adv Study, Simons Ctr Syst Biol, Princeton, NJ 08540 USA. RP Carroll, JS (reprint author), Canc Res UK, Cambridge Res Inst, Li Ku Shing Ctr, Robinson Way, Cambridge CB2 0RE, England. EM jason.carroll@cancer.org.uk OI Brown, Myles/0000-0002-8213-1658 NR 39 TC 26 Z9 29 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 SEP 15 PY 2008 VL 68 IS 18 BP 7380 EP 7385 DI 10.1158/0008-5472.CAN-08-0133 PG 6 WC Oncology SC Oncology GA 351KE UT WOS:000259422400018 PM 18794125 ER PT J AU Stegh, AH Chin, L Louis, DN DePinho, RA AF Stegh, Alexander H. Chin, Lynda Louis, David N. DePinho, Ronald A. TI What drives intense apoptosis resistance and propensity for necrosis in glioblastoma? - A role for Bcl2L12 as a multifunctional cell death regulator SO CELL CYCLE LA English DT Article DE Bcl2L12; alpha B-crystallin; apoptosis; necrosis; glioblastoma; caspase-3 and caspase-7 ID ALPHA-B-CRYSTALLIN; HUMAN-MALIGNANT GLIOMA; MITOCHONDRIAL PERMEABILITY TRANSITION; LIGAND-INDUCED APOPTOSIS; HEAT-SHOCK PROTEINS; X-LINKED INHIBITOR; HUMAN BRAIN-TUMORS; GROWTH-FACTOR; PROGNOSTIC-FACTOR; STRUCTURAL BASIS AB Glioblastoma (GBM) is the most common type of primary brain cancer and carries a dismal prognosis primarily due to the emergence of resistance towards extant radiation, conventional and targeted chemotherapies. Although GBM resists therapy-induced apoptosis, tumors show a seemingly paradoxical propensity for florid intratumoral necrogenesis. This necrosis manifests pathologically as microscopic foci or confluent expanses of necrotic tumor. While it is now well recognized that necrosis is an active cell death process and that apoptosis and necrosis death modalities are intertwined on multiple levels, the precise molecular mechanisms and genetic elements underlying these forms of cell death in GBM remain areas of active investigation. In recent oncogenomic studies, we identified a novel GBM oncoprotein, Bcl2-Like 12 (Bcl2L12), which is significantly expressed in the majority of primary GBM tumor specimens and distantly related to canonical Bcl-2 proteins. Due to its distinctive impact on cell death signaling, Bcl2L12 phenocopies pro-necrotic and anti-apoptotic propensities of high-grade glioma: Mechanistically, we determined that unlike prototypic Bcl-2 family members, Bcl2L12 does not safeguard mitochondrial membrane integrity, but instead potently inhibits apoptosis at the level of post-mitochondrial effector caspase-3/7 activation. A combination of enforced expression, RNAi-mediated extinction, co-localization and protein interaction studies revealed that Bcl2L12 inhibits caspases 3 and 7 via distinct mechanisms. Direct physical interaction underlies Bcl2L12's inhibition of caspase-7 processing, whereas Bcl2L12-induced transcriptional upregulation of the small heat shock protein alpha B-crystallin is instrumental to neutralization of caspase-3 activation. Mirroring the cellular phenotype elicited by energy depletion, genetic or pharmacologic inhibition of post-mitochondrial apoptosis signaling molecules, Bcl2L12 promotes necrogenesis in glial cells in the context of a proapoptotic stimulus establishing that it represents a novel regulator of the balance between apoptosis and necrosis in GBM. C1 [Stegh, Alexander H.; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci, Ctr Appl Canc Sci, Boston, MA 02115 USA. [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Louis, David N.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Stegh, AH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM alexander_stegh@dfci.harvard.edu; ron_depinho@dfci.harvard.edu FU Claudia-Adams Barr; NIH [K99/R00 K99CA129172, PO1 CA95616, RO1 CA099041, RO1 CA57683]; Bernard A. and Wendy J. Goldhirsh Foundation; Christopher Elliot Foundation; Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science FX This work was supported by a Claudia-Adams Barr and a NIH K99/R00 (K99CA129172) award (AHS), NIH grants PO1 CA95616 (RAD, DNL and LC), RO1 CA099041 (LC) and RO1 CA57683 (DNL) and the Bernard A. and Wendy J. Goldhirsh Foundation and the Christopher Elliot Foundation (RAD and LC). RAD is an American Cancer Society Research Professor and supported by the Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science. NR 81 TC 39 Z9 39 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP 15 PY 2008 VL 7 IS 18 BP 2833 EP 2839 DI 10.4161/cc.7.18.6759 PG 7 WC Cell Biology SC Cell Biology GA 348JK UT WOS:000259206600013 PM 18769159 ER PT J AU Drapkin, R Clauss, A Skates, S AF Drapkin, Ronny Clauss, Adam Skates, Steven TI Urokinase-type plasminogen activator receptor: A beacon of malignancy? SO CLINICAL CANCER RESEARCH LA English DT Article ID OVARIAN-CANCER; SURVIVAL AB Discriminating between benign and malignant disease is a pivotal diagnostic issue in the care of women with pelvic masses. Identification of serum biomakers that can rellably make the distinction would aid in the proper referral for patient care and may provide leads in the development of early detection strategies. C1 [Drapkin, Ronny; Clauss, Adam] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Drapkin, Ronny; Clauss, Adam; Skates, Steven] Harvard Univ, Sch Med, Boston, MA USA. [Skates, Steven] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Drapkin, R (reprint author), Dana Farber Canc Inst, Dept Med Oncol, JFB 215D,44 Binney St, Boston, MA 02115 USA. EM ronny_drapkin@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU NCI NIH HHS [U01 CA086381, CA086381, CA105009, CA108748, CA78284, K08 CA108748, K08 CA108748-04, P50 CA105009, P50 CA105009-050003, U01 CA078284, U01 CA078284-05, U01 CA086381-05] NR 14 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2008 VL 14 IS 18 BP 5643 EP 5645 DI 10.1158/1078-0432.CCR-08-1557 PG 3 WC Oncology SC Oncology GA 350JC UT WOS:000259347600001 PM 18794069 ER PT J AU Goetz, MP Suman, VJ Couch, F Ames, MM Rae, JM Erlander, MG Ma, XJ Sgroi, DC Reynolds, CA Lingle, WL Weinshilboum, RM Flockhart, DA Desta, Z Perez, EA Ingle, JN AF Goetz, Matthew P. Suman, Vera J. Couch, FergusJ. Ames, Matthew M. Rae, James M. Erlander, Mark G. Ma, Xiao-Jun Sgroi, Dennis C. Reynolds, Carol A. Lingle, Wilma L. Weinshilboum, Richard M. Flockhart, David A. Desta, Zeruesenay Perez, Edith A. Ingle, James N. TI Cytochrome P450 2D6 and homeobox 13/interleukin-17B receptor: Combining inherited and tumor gene markers for prediction of tamoxifen resistance SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; RECEIVING ADJUVANT TAMOXIFEN; 2-GENE EXPRESSION RATIO; HOT FLASHES; ESTROGEN; CYP2D6; SURVIVAL; WOMEN; METABOLISM; RECURRENCE AB Purpose: Genetic variation in cytochrome P450 2D6 (CYP2D6) and the gene expression ratio of the homeobox 13 (HOXB13) to interleukin-17B receptor (IL17BR) are associated with tamoxifen resistance. We sought to determine the combined effect of inherited (CYP2D6) and somatic (HOXB13/IL17BR) gene variation in tamoxifen-treated breast cancer. Experimental Design: Retrospective analysis of women with node-negative breast cancer randomized to receive 5 years of tamoxifen (North Central Cancer Treatment Group 89-30-52). CYP2D6 metabolism (extensive or decreased) was based on CYP2D6*4 genotype and presence/absence of a CYP2D6 inhibitor. Reverse transcription-PCR profiles for HOXB13 and IL17BR and the cut point separating patients into high- and low-risk categories according to disease-free survival (DFS) were used. A risk factor (CYP2D6:HOXB13/IL17BR) representing the four categories of combining CYP2D6 metabolism (extensive or decreased) and HOXB13/IL17BR (low or high) was created. The association between CYP2D6:HOXB13/IL17BR and DFS and overall survival (OS) was assessed using the log-rank test and proportional hazards modeling. Results: CYP2D6 metabolism and HOXB13/IL17BR gene ratio was available in 110 of 160 (69%) patients. The combined CYP2D6:HOXB13/IL17BR risk factor was significantly associated with DFS (log-rank P = 0.004) and OS (P = 0.009). Relative to women with extensive CYP2D6 metabolism and low HOXB13/IL17BR, those with either decreased metabolism or a high HOXB13/IL17BR ratio had significantly worse CS (adjusted hazard ratio, 2.41; 95% confidence interval, 1.08-5.37; P = 0.031), whereas women with both decreased metabolism and high HOXB13/IL17BR ratio had the shortest survival (adjusted hazard ratio, 3.15; 95% Cl, 1.17-8.52; P = 0.024). Conclusions: An index composed of inherited (CYP2D6) and tumor (HOXB13/IL17BR) gene variation identifies patients with varying degrees of resistance to tamoxifen. C1 [Goetz, Matthew P.; Ingle, James N.] Mayo Clin, Coll Med, Dept Oncol, Rochester, MN 55905 USA. [Suman, Vera J.] Mayo Clin, Coll Med, Dept Biostat, Rochester, MN 55905 USA. [Couch, FergusJ.; Reynolds, Carol A.; Lingle, Wilma L.] Mayo Clin, Coll Med, Dept Pathol, Rochester, MN 55905 USA. [Goetz, Matthew P.; Ames, Matthew M.; Weinshilboum, Richard M.] Mayo Clin, Coll Med, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA. [Rae, James M.] Univ Michigan, Sch Med, Dept Med, Div Hematol Oncol, Ann Arbor, MI 48104 USA. [Erlander, Mark G.; Ma, Xiao-Jun] AviaraDx, San Diego, CA USA. [Sgroi, Dennis C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Mol Pathol Res Unit, Boston, MA 02115 USA. [Flockhart, David A.; Desta, Zeruesenay] Indiana Univ, Dept Med, Div Clin Pharmacol, Indianapolis, IN USA. [Perez, Edith A.] Mayo Clin, Dept Med, Div Hematol & Oncol, Jacksonville, FL 32224 USA. RP Goetz, MP (reprint author), Mayo Clin, Coll Med, Dept Oncol, 200 1st St SW, Rochester, MN 55905 USA. EM goetz.matthew@mayo.edu FU Paul Calabresi Program [CA 90628]; Mayo Clinic Breast Cancer Specialized Program [CA116201]; Mayo Comprehensive Cancer Center [CA 15083, CA87898]; Breast Cancer Research Foundation; National Institute of General Medical Sciences [U-01 GM61388]; North Central CancerTreatment Group [CA-25224] FX Paul Calabresi Program in Clinical-Translational Research at Mayo Clinic grant CA 90628 (M.P. Goetz), Mayo Clinic Breast Cancer Specialized Program of Research Excellence grant CA116201 (J.N. Ingle, F.J. Couch, M.P. Goetz, V.J. Suman, and C.A. Reynolds), Mayo Comprehensive Cancer Center grant CA 15083 (M.M. Ames), CA87898 (F.J. Couch), Breast Cancer Research Foundation (J.M. Rae and E.A. Perez), National Institute of General Medical Sciences (Bethesda, MID) grant U-01 GM61388 (R.M.Weinshilboum, M.P. Goetz, and J.N. Ingle), and CA-25224 (North Central CancerTreatment Group). NR 29 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2008 VL 14 IS 18 BP 5864 EP 5868 DI 10.1158/1078-0432.CCR-08-0619 PG 5 WC Oncology SC Oncology GA 350JC UT WOS:000259347600031 PM 18794098 ER PT J AU Miles, WO Jaffray, E Campbell, SG Takeda, S Bayston, LJ Basu, SP Li, MF Raftery, LA Ashe, MP Hay, RT Ashe, HL AF Miles, Wayne O. Jaffray, Ellis Campbell, Susan G. Takeda, Shugaku Bayston, Laura J. Basu, Sanjay P. Li, Mingfa Raftery, Laurel A. Ashe, Mark P. Hay, Ronald T. Ashe, Hilary L. TI Medea SUMOylation restricts the signaling range of the Dpp morphogen in the Drosophila embryo SO GENES & DEVELOPMENT LA English DT Article DE SUMO; morphogen; medea; dpp; Drosophila embryo ID GROWTH-FACTOR-BETA; KAPPA-B ACTIVATION; NUCLEAR EXPORT; CAENORHABDITIS-ELEGANS; SUMO-1 MODIFICATION; TRANSCRIPTIONAL ACTIVITY; ACTIVITY GRADIENT; TUMOR-SUPPRESSOR; CONJUGATION; PROTEIN AB Morphogens are secreted signaling molecules that form concentration gradients and control cell fate in developing tissues. During development, it is essential that morphogen range is strictly regulated in order for correct cell type specification to occur. One of the best characterized morphogens is Drosophila Decapentaplegic (Dpp), a BMP signaling molecule that patterns the dorsal ectoderm of the embryo by activating the Mad and Medea (Med) transcription factors. We demonstrate that there is a spatial and temporal expansion of the expression patterns of Dpp target genes in SUMO pathway mutant embryos. We identify Med as the primary SUMOylation target in the Dpp pathway, and show that failure to SUMOylate Med leads to the increased Dpp signaling range observed in the SUMO pathway mutant embryos. Med is SUMO modified in the nucleus, and we provide evidence that SUMOylation triggers Med nuclear export. Hence, Med SUMOylation provides a mechanism by which nuclei can continue to monitor the presence of extracellular Dpp signal to activate target gene expression for an appropriate duration. Overall, our results identify an unusual strategy for regulating morphogen range that, rather than impacting on the morphogen itself, targets an intracellular transducer. C1 [Miles, Wayne O.; Campbell, Susan G.; Takeda, Shugaku; Bayston, Laura J.; Basu, Sanjay P.; Ashe, Mark P.; Ashe, Hilary L.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. [Jaffray, Ellis; Hay, Ronald T.] Univ Dundee, Sch Life Sci, Dundee DD1 5EH, Scotland. [Li, Mingfa; Raftery, Laurel A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02109 USA. [Li, Mingfa; Raftery, Laurel A.] Harvard Univ, Sch Med, Charlestown, MA 02109 USA. RP Ashe, HL (reprint author), Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. EM hilary.ashe@manchester.ac.uk RI Hay, Ronald/F-9338-2011; Raftery, Laurel/H-1406-2012 OI Hay, Ronald/0000-0001-7113-9024; Raftery, Laurel/0000-0003-4797-4163 FU Wellcome [077341/Z/05/Z, 080349/Z/06/Z]; [NIGMS] FX We thank David J. Sutherland, Svetlana Korochkina, and Viet Le for technical support; G. Pyrowolakis, M. Affolter, L. Alphey, L. Goldstein, A. Laughon, M. Peifer, and P. Rorth for plasmids; S. Tanda and K. Wharton for flies; P. ten Dijke and H. Jackle for the pMad and Kr antibodies, respectively; C. Hill for MDA-MB468 cells; S. Brown for advice; and R. Harris and A. Sawala for comments on the manuscript. This work was supported by a Wellcome grants to H. L. A. (077341/Z/05/Z) and M. P. A. (080349/Z/06/Z). The Raftery laboratory was supported by NIGMS. NR 68 TC 27 Z9 27 U1 0 U2 6 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 SEP 15 PY 2008 VL 22 IS 18 BP 2578 EP 2590 DI 10.1101/gad.494808 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 348OY UT WOS:000259221000012 PM 18794353 ER PT J AU Geier, C Gehmlich, K Ehler, E Hassfeld, S Perrot, A Hayess, K Cardim, N Wenzel, K Erdmann, B Krackhardt, F Posch, MG Bublak, A Naegele, H Scheffold, T Dietz, R Chien, KR Spuler, S Furst, DO Nurnberg, P Ozcelik, C AF Geier, Christian Gehmlich, Katja Ehler, Elisabeth Hassfeld, Sabine Perrot, Andreas Hayess, Katrin Cardim, Nuno Wenzel, Katrin Erdmann, Bettina Krackhardt, Florian Posch, Maximilian G. Bublak, Angelika Naegele, Herbert Scheffold, Thomas Dietz, Rainer Chien, Kenneth R. Spuler, Simone Fuerst, Dieter O. Nuernberg, Peter Oezcelik, Cemil TI Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy SO HUMAN MOLECULAR GENETICS LA English DT Article ID MUSCLE LIM PROTEIN; HEART-FAILURE; DILATED CARDIOMYOPATHY; SKELETAL-MUSCLE; DISEASE; MLP; TITIN; GENE; ABNORMALITIES; POPULATION AB Hypertrophic cardiomyopathy (HCM) is a frequent genetic cardiac disease and the most common cause of sudden cardiac death in young individuals. Most of the currently known HCM disease genes encode sarcomeric proteins. Previous studies have shown an association between CSRP3 missense mutations and either dilated cardiomyopathy (DCM) or HCM, but all these studies were unable to provide comprehensive genetic evidence for a causative role of CSRP3 mutations. We used linkage analysis and identified a CSRP3 missense mutation in a large German family affected by HCM. We confirmed CSRP3 as an HCM disease gene. Furthermore, CSRP3 missense mutations segregating with HCM were identified in four other families. We used a newly designed monoclonal antibody to show that muscle LIM protein (MLP), the protein encoded by CSRP3, is mainly a cytosolic component of cardiomyocytes and not tightly anchored to sarcomeric structures. Our functional data from both in vitro and in vivo analyses suggest that at least one of MLP's mutated forms seems to be destabilized in the heart of HCM patients harbouring a CSRP3 missense mutation. We also present evidence for mild skeletal muscle disease in affected persons. Our results support the view that HCM is not exclusively a sarcomeric disease and also suggest that impaired mechano-sensory stress signalling might be involved in the pathogenesis of HCM. C1 [Geier, Christian; Hassfeld, Sabine; Krackhardt, Florian; Dietz, Rainer; Oezcelik, Cemil] Charite Univ Med Berlin, Campus Virchow Klinikum, Med Klin MS Kardiol, D-13353 Berlin, Germany. [Geier, Christian; Perrot, Andreas; Wenzel, Katrin; Posch, Maximilian G.; Dietz, Rainer; Oezcelik, Cemil] Max Delbruck Ctr Mol Med, ECRC, D-13125 Berlin, Germany. [Gehmlich, Katja] UCL, Dept Med, London WC1E 6DD, England. [Ehler, Elisabeth] Kings Coll London, Randall Div Cell & Mol Biophys, London SE1 1UL, England. [Ehler, Elisabeth] Kings Coll London, Div Cardiovasc, London SE1 1UL, England. [Hayess, Katrin] Bundesinst Risikobewertung ZEBET, D-12277 Berlin, Germany. [Cardim, Nuno] Univ Nova Lisboa, Fac Ciencias Med, P-1700093 Lisbon, Portugal. [Erdmann, Bettina] Max Delbruck Ctr Mol Med Berlin Buch, D-13125 Berlin, Germany. [Bublak, Angelika] DRK Kliniken Berlin Kopenick, Med Klin 1, D-12559 Berlin, Germany. [Naegele, Herbert] Krankenhaus Reinbek, Med Klin, D-21465 Hamburg, Germany. [Scheffold, Thomas] Univ Witten Herdecke, Inst Herz Kreislaufforsch, D-44225 Dortmund, Germany. [Chien, Kenneth R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Cell Biol, Harvard Stem Cell Inst,Cardiovasc Res Ctr, Boston, MA 02114 USA. [Spuler, Simone] Charite Univ Med Berlin, ECRC, Muscle Res Unit, D-13125 Berlin, Germany. [Fuerst, Dieter O.] Univ Bonn, Inst Zellbiol, Abt Mol Zellbiol, D-53121 Bonn, Germany. [Nuernberg, Peter] Univ Cologne, Cologne Ctr Genom, D-50674 Cologne, Germany. [Nuernberg, Peter] Univ Cologne, Inst Genet, D-50674 Cologne, Germany. RP Geier, C (reprint author), Charite Univ Med Berlin, Campus Virchow Klinikum, Med Klin MS Kardiol, Augustenburger Pl 1, D-13353 Berlin, Germany. EM christian.geier@charite.de RI Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013; OI Ehler, Elisabeth/0000-0001-5646-5964 FU Max Delbruck Center for Molecular Medicine Berlin-Buch; German Federal Ministry of Science and Education through the National Genome Research Network; German Competence Network Heart Failure (Kompetenznetz Herzinsuffizienz); Charite Universitatsmedizin Berlin; Berlin Institute of Heart Research (BIHR); Helmholtz-Gemeinschaft; Deutsche Forschungsgemeinschaft [KFG192] FX This study was supported in part by the Max Delbruck Center for Molecular Medicine Berlin-Buch (to C. G.), the German Federal Ministry of Science and Education through the National Genome Research Network (to P. N.) and the German Competence Network Heart Failure (Kompetenznetz Herzinsuffizienz), by the Charite Universitatsmedizin Berlin, and the Berlin Institute of Heart Research (BIHR), a virtual institute funded by the Helmholtz-Gemeinschaft, and the Deutsche Forschungsgemeinschaft (grant KFG192 to S. Spuler). NR 50 TC 60 Z9 61 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 15 PY 2008 VL 17 IS 18 BP 2753 EP 2765 DI 10.1093/hmg/ddn160 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 343OK UT WOS:000258863200001 PM 18505755 ER PT J AU Griesemer, AD LaMattina, JC Okumi, M Etter, JD Shimizu, A Sachs, DH Yamada, K AF Griesemer, Adam D. LaMattina, John C. Okumi, Masayoshi Etter, Justin D. Shimizu, Akira Sachs, David H. Yamada, Kazuhiko TI Linked suppression across an MHC-mismatched barrier in a miniature swine kidney transplantation model SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; CARDIAC ALLOGRAFT; DENDRITIC CELLS; RENAL-ALLOGRAFTS; TOLERANCE; CD4(+)CD25(+); INDUCTION; IMMUNOSUPPRESSION; RECOGNITION; MOLECULE AB We have demonstrated previously that a 12-day course of FK506 permits the induction of tolerance to fully MHC-mismatched renal transplants in miniature swine. In the present study, we examined the mechanism of this tolerance by assessing the possibility that the survival of one-haplotype mismatched third-party kidneys might be prolonged via linked suppression. Ten SLA(d/d) miniature swine received fully MHC-mismatched renal allografts from SLA(c/c) donors with 12 days of FK506. Six animals received second SLA(c/c) kidneys without immunosuppression to confirm tolerance. Regulatory mechanisms were assessed by mixed lymphocyte reaction (MLR) and cell-mediated lympholysis coculture assays and ELISA for regulatory cytokines. Linked suppression was investigated by transplanting SLA(a/c) or SLA(a/d) allografts into long-term tolerant recipients without immunosuppression. All recipients showed donor-specific unresponsiveness in standard cell-mediated lympholysis and NILR assays. Tolerant cells prestimulated with donor Ag and then cocultured with naive recipient MHC-matched cells inhibited antidonor responses, confirming the presence of regulatory cells. ELISA and NILR assays showed that TGF-beta 2 was involved in mediating the suppression in vitro. SLA(a/d) renal allografts transplanted into tolerant recipients were rejected by postoperative day 8 (median, 7 days; range, 6-8). In contrast, SLA(a/c) allografts showed markedly prolonged survival (median, 52 days; range, 28-78; p = 0.0246), suggesting linked suppression. Animals not challenged with a second donor-matched graft did not manifest linked suppression consistent with in vitro data showing that re-exposure to tolerated Ags is import-ant for generation of regulatory cells. To our knowledge, these data represent the first evidence of linked suppression across fully MHC-mismatched barriers in a large animal model. C1 [Yamada, Kazuhiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Organ Transplantat Tole, Boston, MA 02129 USA. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Organ Transplantat Tole, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu RI LaMattina, John/B-2976-2014 OI LaMattina, John/0000-0001-7016-0382 FU National Institutes of Health [R37 A131046-16]; American Society of Transplantation/Juvenile Diabetes Research Foundation Fellowship FX This work was supported by grants from the National Institutes of Health (R37 A131046-16) and A.G. received support from the American Society of Transplantation/Juvenile Diabetes Research Foundation Fellowship. NR 34 TC 23 Z9 23 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2008 VL 181 IS 6 BP 4027 EP 4036 PG 10 WC Immunology SC Immunology GA 349AE UT WOS:000259250400038 PM 18768858 ER PT J AU Fehr, T Wang, S Haspot, F Kurtz, J Blaha, P Hogan, T Chittenden, M Wekerle, T Sykes, M AF Fehr, Thomas Wang, Sophia Haspot, Fabienne Kurtz, Josef Blaha, Peter Hogan, Timothy Chittenden, Meredith Wekerle, Thomas Sykes, Megan TI Rapid deletional peripheral CD8 T cell tolerance induced by allogeneic bone marrow: Role of donor class II MHC and B cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RENAL-ALLOGRAFT TOLERANCE; DENDRITIC CELLS; IN-VIVO; HEMATOPOIETIC CHIMERISM; TRANSPLANTATION TOLERANCE; MONOCLONAL-ANTIBODY; PEPTIDE COMPLEXES; STEM-CELLS; INDUCTION; EXOSOMES AB Mixed chimerism and donor-specific tolerance are achieved in mice receiving 3 Gy of total body irradiation and anti-CD154 mAb followed by, allogeneic bone marrow (BM) transplantation. In this model, recipient CD4 cells are critically important for CD8 tolerance. To evaluate the role of CD4 cells recognizing donor MHC class II directly, we used class II-deficient donor marrow and were not able to achieve chimerism unless recipient CD8 cells were depleted, indicating that directly alloreactive CD4 cells were necessary, for CD8 tolerance. To identify the MHC class II+ donor cells promoting this tolerance, we used donor BM lacking certain cell populations or used positively selected cell populations. Neither donor CD11c(+) dendritic cells, B cells, T cells, nor donor-derived IL-10 were critical for chimerism induction. Purified donor B cells induced early chimerism and donor-specific cell-mediated lympholysis tolerance in both strain combinations tested. In contrast, positively selected CD11b(+) monocytes/myeloid cells did not induce early chimerism in either strain combination. Donor cell preparations containing B cells were able to induce early deletion of donor-reactive TCR-transgenic 2C CD8 T cells, whereas those devoid of B cells had reduced activity. Thus, induction of stable mixed chimerisin depends on the expression of MHC class 11 on the donor marrow, but no requisite donor cell lineage was identified. Donor BM-derived B cells induced early chimerism, donor-specific cell-mediated lympholysis tolerance, and deletion of donor-reactive CD8 T cells, whereas CD11b(+) cells did not. Thus, BM-derived B cells are potent tolerogenic APCs for alloreactive CD8 cells. C1 [Fehr, Thomas; Wang, Sophia; Haspot, Fabienne; Kurtz, Josef; Hogan, Timothy; Chittenden, Meredith; Sykes, Megan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Blaha, Peter; Wekerle, Thomas] Med Univ Vienna, Vienna Gen Hosp, Div Transplantat, Dept Surg, Vienna, Austria. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E Bldg 149-5102,13th St, Boston, MA 02129 USA. EM mgh@harvard.edu OI Wekerle, Thomas/0000-0001-5159-2796 FU National Institutes of Health [R01 HL49915]; Swiss Foundation for Medical and Biological Grants; Walter and Gertrud Siegenthaler Foundation (Medical Faculty, University of Zurich, Switzerland); Fondation pour la Recherche Medicale (France); American Society of Blood and Marrow Transplantation FX This work was supported by National Institutes of Health Grant R01 HL49915. T.F. was supported by a research fellowship from the Swiss Foundation for Medical and Biological Grants (with support from Novartis Switzerland) and a research fellowship from the Walter and Gertrud Siegenthaler Foundation (Medical Faculty. University of Zurich, Switzerland). F.H. Was Supported by a research fellowship from the Fondation pour la Recherche Medicale (France) and a research fellowship from the American Society of Blood and Marrow Transplantation. NR 54 TC 20 Z9 22 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2008 VL 181 IS 6 BP 4371 EP 4380 PG 10 WC Immunology SC Immunology GA 349AE UT WOS:000259250400076 PM 18768896 ER PT J AU Nakagawa, K Sheikh, SI Snuderl, M Frosch, MP Greenberg, SM AF Nakagawa, Kazuma Sheikh, Sarah I. Snuderl, Matija Frosch, Matthew P. Greenberg, Steven M. TI A new Thr49Pro transthyretin gene mutation associated with leptomeningeal amyloidosis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE transthyretin; oculoleptomeningeal amyloidosis; hereditary leptomeningeal TTR amyloidosis; familial amyloid polyneuropathy ID OCULOLEPTOMENINGEAL AMYLOIDOSIS; MENINGOCEREBROVASCULAR AMYLOIDOSIS; POLYNEUROPATHY; NEURODEGENERATION; HEMORRHAGE; VARIANTS AB Leptomeningeal amyloidosis is a rare central nervous system manifestation of systemic amyloidosis from transthyretin (TTR) mutation. Tell TTR gene mutations associated with this condition have been described. We report the clinical, radiological, and pathological features of a case of leptomeningeal amyloidosis from a novel Thr49Pro TTR gene mutation. A 53 year-old man presented with recurrent episodes of transient aphasia and right hand stiffness, headaches, and peripheral neuropathy. A surgical biopsy of the leptomeninges and superficial cortex, and DNA sequences of the TTR gene were analyzed. Elevated cerebrospinal fluid (CSF) protein and diffuse leptomeningeal enhancement of the neuraxis from the cortical sulci to the cauda equina on contrast MRI were the defining clinical features. A surgical biopsy revealed TTR amyloid deposition in the subpia and within the leptomeningeal blood vessels. DNA sequencing showed a proline-for-threonine Substitution at codon 49 of the TTR, gene in one allele. A novel Thr49Pro TTR gene mutation is associated with leptomeningeal amyloidosis resulting in recurrent CNS symptoms. (C) 2008 Elsevier B.V. All rights reserved. C1 [Nakagawa, Kazuma; Sheikh, Sarah I.; Snuderl, Matija; Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Nakagawa, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, WACC 835,55 Fruit St, Boston, MA 02114 USA. EM kazuman1@hotmail.com OI Snuderl, Matija/0000-0003-0752-0917 NR 21 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD SEP 15 PY 2008 VL 272 IS 1-2 BP 186 EP 190 DI 10.1016/j.jns.2008.05.014 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 347HM UT WOS:000259131200029 PM 18579156 ER PT J AU Li, HT Louey, JWC Choy, KW Liu, DTL Chan, WM Chan, YM Fung, NSK Fan, BJ Baum, L Chan, JCN Lam, DSC Pang, CP AF Li, Haitao Louey, Janice W. C. Choy, Kwong Wai Liu, David T. L. Chan, Wai Man Chan, Yiu Man Fung, Nicholas S. K. Fan, Bao Jian Baum, Larry Chan, Juliana C. N. Lam, Dennis S. C. Pang, Chi Pui TI EDN1 Lys198Asn is associated with diabetic retinopathy in type 2 diabetes SO MOLECULAR VISION LA English DT Article ID OXIDE SYNTHASE GENE; NITRIC-OXIDE; ENDOTHELIN-1 GENE; BLOOD-PRESSURE; ALPHA-2-BETA-1 INTEGRIN; POLYMORPHISMS; EXPRESSION; PROGRESSION; MELLITUS AB Purpose: We tested the hypothesis that genetic variants in vasoactive and angiogenic factors regulating the retina vasculature contribute to the development of diabetic retinopathy (DR). Methods: A case-control study was performed to study the genetic association between DR and polymorphic variants of EDN1 (Lys198Asn), LTA (IVS1-80C>A, IVS1-206G>C, IVS1-252A>G), eNOS (Glu298Asp), and ITGA2 (BgI II) in a Chinese population with type 2 diabetes mellitus. A well defined population with type 2 diabetes, consisting of 127 controls and 216 DR patients, was recruited. Results: A higher frequency of the Asn/Asn genotype of EDN1 was found in individuals with at least 10 years of diabetes and no retinopathy (controls) compared with DR patients with any duration of diabetes (DR: 2.3%; control: 11.0%; p=0.0002). The Asn allele was also more frequent in controls than DR patients (DR: 16.4%; control: 29.5%; p=0.007). Multiple logistic regression analysis showed that the Asn/Asn genotype was the factor most significantly associated with reduced risk of DR (odds ratio=0.19; 95% CI: 0.07-0.53; p=0.002) and with late onset of diabetes (Asn/Asn: 59 years; Lys/Lys + Lys/Asn: 53 years; p=0.02). Moreover, the Lys/Lys genotype was more common among patients with nonproliferative (75.7%) than proliferative DR (56.9%; p=0.008). The distributions of Lys198Asn alleles in hypertension did not differ from normotensive subjects. No associations between DR and polymorphisms of LTA, eNOS, or ITGA2 were detected, and there were no detectable gene-gene or gene-environmental interactions among the polymorphisms. Conclusions: The Asn/Asn genotype of EDN1 was associated with a reduced risk of DR and with delayed onset of type 2 diabetes. C1 [Li, Haitao; Louey, Janice W. C.; Liu, David T. L.; Chan, Wai Man; Fung, Nicholas S. K.; Fan, Bao Jian; Lam, Dennis S. C.; Pang, Chi Pui] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China. [Louey, Janice W. C.] Univ Melbourne, Fac Med Dent & Hlth Sci, Melbourne, Vic 3010, Australia. [Choy, Kwong Wai; Chan, Yiu Man] Chinese Univ Hong Kong, Dept Obstet & Gynecol, Hong Kong, Hong Kong, Peoples R China. [Chan, Wai Man] Hong Kong Sanat & Hosp, Dept Ophthalmol, Hong Kong, Hong Kong, Peoples R China. [Fan, Bao Jian] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Baum, Larry; Chan, Juliana C. N.] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. RP Pang, CP (reprint author), Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong Eye Hosp, 147K Argyle St, Kowloon, Hong Kong, Peoples R China. EM cppang@cuhk.edu.hk RI Hossain, Sarah /C-7332-2009; Baum, Lawrence/B-1005-2013; Pang, Chi/I-5388-2014; Chan, Juliana /B-7918-2016 OI Fan, Baojian/0000-0002-6851-2737; Hossain, Sarah /0000-0003-1355-0979; Baum, Lawrence/0000-0002-5345-9355; Chan, Juliana /0000-0003-1325-1194 FU Chinese University of Hong Kong; Li Ka Shing Foundation; Ophthalmology research and training fund FX We are grateful to patients for their participation in this study. This study is supported by a block grant of the Chinese University of Hong Kong and the Li Ka Shing Foundation, Ophthalmology research and training fund. NR 32 TC 16 Z9 16 U1 1 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD SEP 15 PY 2008 VL 14 IS 200-03 BP 1698 EP 1704 PG 7 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 376BI UT WOS:000261157600002 PM 18806884 ER PT J AU Yelin, D Bouma, BE Rosowsky, JJ Tearney, GJ AF Yelin, Dvir Bouma, B. E. Rosowsky, J. J. Tearney, G. J. TI Doppler imaging using spectrally-encoded endoscopy SO OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; TWIN-TRANSFUSION-SYNDROME; LASER-DOPPLER; BLOOD-FLOW; HIGH-SPEED; MICROSCOPY; MANAGEMENT; MEMBRANE; SURGERY; SPECKLE AB The capability to image tissue motion such as blood flow through an endoscope could have many applications in medicine. Spectrally encoded endoscopy (SEE) is a recently introduced technique that utilizes a single optical fiber and miniature diffractive optics to obtain endoscopic images through small diameter probes. Using spectral-domain interferometry, SEE is furthermore capable of three-dimensional volume imaging at video rates. Here we show that by measuring relative spectral phases, this technology can additionally measure Doppler shifts. Doppler SEE is demonstrated in flowing Intralipid phantoms and vibrating middle ear ossicles. (C) 2008 Optical Society of America. C1 [Yelin, Dvir] Technion Israel Inst Technol, Dept Biomed Engn, IL-32000 Haifa, Israel. [Rosowsky, J. J.] Harvard Univ, Sch Med, Eaton Peabody Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Bouma, B. E.; Tearney, G. J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Rosowsky, J. J.] Harvard Univ, Sch Med, Dept Otol & Laryngol & Hlth Sci & Technol, Boston, MA 02114 USA. RP Yelin, D (reprint author), Technion Israel Inst Technol, Dept Biomed Engn, IL-32000 Haifa, Israel. EM yelin@bm.technion.ac.il FU Center for Integration of Medicine; Innovative Technology; National Science Foundation [BES-0086709]; NIH/NIBIB [1R21EB007718-01] FX This study was funded in part by the Center for Integration of Medicine and Innovative Technology, a National Science Foundation grant (BES-0086709) and the NIH/NIBIB 1R21EB007718-01 NR 31 TC 13 Z9 15 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD SEP 15 PY 2008 VL 16 IS 19 BP 14836 EP 14844 DI 10.1364/OE.16.014836 PG 9 WC Optics SC Optics GA 349HM UT WOS:000259271900055 PM 18795020 ER PT J AU Chang, HCH Dimlich, DN Yokokura, T Mukherjee, A Kankel, MW Sen, A Sridhar, V Fulga, TA Hart, AC Van Vactor, D Artavanis-Tsakonas, S AF Chang, Howard Chia-Hao Dimlich, Douglas N. Yokokura, Takakazu Mukherjee, Ashim Kankel, Mark W. Sen, Anindya Sridhar, Vasanthi Fulga, Tudor A. Hart, Anne C. Van Vactor, David Artavanis-Tsakonas, Spyros TI Modeling Spinal Muscular Atrophy in Drosophila SO PLOS ONE LA English DT Article AB Spinal Muscular Atrophy (SMA), a recessive hereditary neurodegenerative disease in humans, has been linked to mutations in the survival motor neuron (SMN) gene. SMA patients display early onset lethality coupled with motor neuron loss and skeletal muscle atrophy. We used Drosophila, which encodes a single SMN ortholog, survival motor neuron (Smn), to model SMA, since reduction of Smn function leads to defects that mimic the SMA pathology in humans. Here we show that a normal neuromuscular junction (NMJ) structure depends on SMN expression and that SMN concentrates in the postsynaptic NMJ regions. We conducted a screen for genetic modifiers of an Smn phenotype using the Exelixis collection of transposon-induced mutations, which affects approximately 50% of the Drosophila genome. This screen resulted in the recovery of 27 modifiers, thereby expanding the genetic circuitry of Smn to include several genes not previously known to be associated with this locus. Among the identified modifiers was wishful thinking (wit), a type II BMP receptor, which was shown to alter the Smn NMJ phenotype. Further characterization of two additional members of the BMP signaling pathway, Mothers against dpp (Mad) and Daughters against dpp (Dad), also modify the Smn NMJ phenotype. The NMJ defects caused by loss of Smn function can be ameliorated by increasing BMP signals, suggesting that increased BMP activity in SMA patients may help to alleviate symptoms of the disease. These results confirm that our genetic approach is likely to identify bona fide modulators of SMN activity, especially regarding its role at the neuromuscular junction, and as a consequence, may identify putative SMA therapeutic targets. C1 [Chang, Howard Chia-Hao; Dimlich, Douglas N.; Yokokura, Takakazu; Kankel, Mark W.; Sen, Anindya; Sridhar, Vasanthi; Fulga, Tudor A.; Van Vactor, David; Artavanis-Tsakonas, Spyros] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02163 USA. [Mukherjee, Ashim] Banaras Hindu Univ, Dept Mol & Human Genet, Varanasi 221005, Uttar Pradesh, India. [Hart, Anne C.] Harvard Univ, Sch Med, Canc Ctr, Massachusetts Gen Hosp, Dept Pathol, Cambridge, MA 02138 USA. [Artavanis-Tsakonas, Spyros] Coll France, Paris, France. RP Chang, HCH (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02163 USA. EM artavanis@hms.harvard.edu FU SMA foundation; NIH FX SMA foundation, NIH NR 66 TC 82 Z9 83 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 SEP 15 PY 2008 VL 3 IS 9 AR e3209 DI 10.1371/journal.pone.0003209 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 422KX UT WOS:000264427700004 PM 18791638 ER PT J AU Fall, K Stark, JR Mucci, LA Chan, J Stampfer, MJ Kurth, T Febbo, PG Kantoff, P Ma, J AF Fall, K. Stark, J. R. Mucci, L. A. Chan, J. Stampfer, M. J. Kurth, T. Febbo, P. G. Kantoff, P. Ma, J. TI No association between a polymorphic variant of the IRS-1 gene and prostate cancer risk SO PROSTATE LA English DT Article DE prostate cancer; IRS-1 genotype; IFG-1 pathway ID INSULIN-RECEPTOR SUBSTRATE-1; AMINO-ACID POLYMORPHISM; IGF BINDING PROTEIN-3 AB OBJECTIVE. Insulin receptor substrate-1 (IRS-1) acts as a docking protein between the insulin-like growth factor-1 (IGF-1) receptor and intracellular signaling molecules in the IGF-1 signaling pathway. Accumulating data support a role of IGF-1 in prostate carcinogenesis. We assessed the influence of the most common IRS-1 gene polymorphism (Gly972Arg) on prostate cancer risk, alone and in combination with IGF-1 and other components in the IGF-1 signaling pathway. MATERIALS AND METHODS. In a nested case-control study within the Physicians' Health Study, the IRS-1 polymorphism was assayed from prospectively collected samples from 564 incident prostate cancer cases and 758 controls matched on age and smoking. We calculated relative risks (RR) and 95% confidence intervals (CI) using conditional logistic regression. RESULTS. Among the controls, 0.8% were homozygous (AA) and 12% were heterozygous (GA) for the polymorphic allele. There was no association between carriage of the A allele and total prostate cancer risk (RR 1.195% CI = 0.8-1.5), advanced disease (stage C or D or lethal prostate cancer, RR = 1.3 95% CI = 0.8-2.3), or plasma IGF-1 levels. We explored possible interactions with body mass index and components in the IGF-1 pathway including IGFBP3, PI3k, and PTEN but none of these factors influenced the relation between IRS-1 genotype and prostate cancer risk. CONCLUSIONS. Our data do not support an association between carriage of the variant IRS-1 gene and prostate cancer risk. C1 [Fall, K.; Stark, J. R.; Mucci, L. A.; Stampfer, M. J.; Ma, J.] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. [Fall, K.; Stark, J. R.; Mucci, L. A.; Stampfer, M. J.; Ma, J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Fall, K.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Fall, K.; Stark, J. R.; Mucci, L. A.; Stampfer, M. J.; Kurth, T.; Ma, J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chan, J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Chan, J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Kurth, T.] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA USA. [Febbo, P. G.] Duke Univ, Sch Med, Durham, NC USA. [Kantoff, P.] Dana Farber Canc Inst, Div Solid Tumor Oncol, Boston, MA 02115 USA. RP Fall, K (reprint author), Harvard Univ, Sch Med, Channing Lab, 181 Longwood Ave,3rd floor, Boston, MA 02115 USA. EM katja.fall@ki.se RI Rider, Jennifer/A-5371-2011; Fall, Katja/A-9186-2012; Kurth, Tobias/A-9243-2012; OI Kurth, Tobias/0000-0001-7169-2620; Fall, Katja/0000-0002-3649-2639 FU National Cancer Institute [5R01CA058684-13, CA 097193, CA 42182, CA 90598, CA 34944, CA 40360]; National Heart, Lung and Blood Institute Bethesda MD [HL-26490, HL-34595]; US DOD; National Research Service Award Training Program in Cancer Epidemiology [T32 CA009001-32] FX This work was supported by a grant from the National Cancer Institute (5R01CA058684-13). The Physicians Health Study is supported by grants CA 34944 and CA 40360 from the National Cancer Institute, and grants HL-26490 and HL-34595 from the National Heart, Lung and Blood Institute Bethesda MD. KF was partly supported by a Post Doctoral Traineeship Award from the US DOD. JRS was supported by the National Research Service Award Training Program in Cancer Epidemiology (T32 CA009001-32). NR 14 TC 4 Z9 4 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD SEP 15 PY 2008 VL 68 IS 13 BP 1416 EP 1420 DI 10.1002/pros.20797 PG 5 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 344FO UT WOS:000258912500006 PM 18615538 ER PT J AU Falutz, J Allas, S Mamputu, JC Potvin, D Kotler, D Somero, M Berger, D Brown, S Richmond, G Fessel, J Turner, R Grinspoon, S AF Falutz, Julian Allas, Soraya Mamputu, Jean-Claude Potvin, Diane Kotler, Donald Somero, Michael Berger, Daniel Brown, Stephen Richmond, Gary Fessel, Jeffrey Turner, Ralph Grinspoon, Steven TI Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation SO AIDS LA English DT Article; Proceedings Paper CT 15th Conference on Retroviruses and Opportunistic Infections CY FEB 03-06, 2008 CL Boston, MA DE central fat accumulation; growth hormone-releasing factor; HIV lipodystrophy; safety ID ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK; DEFICIENT CHILDREN; BODY-COMPOSITION; MEN AB Objective: Treatment of HIV patients with daily tesamorelin, a growth hormone-releasing factor analogue, for 26 weeks resulted in a significant decrease in visceral adipose tissue (VAT) and improvement in lipids. The objective of the 26-week extension phase was to evaluate long-term safety and effects of tesamorelin. Design: HIV patients with central fat accumulation in the context of antiretroviral therapy were randomized to tesamorelin 2 mg (n=273) or placebo (n=137) s.c. daily for 26 weeks. At week 26, patients originally on tesamorelin were rerandomized to 2 mg tesamorelin (T-T group, n=154) or placebo (T-P group, n=50), whereas patients originally on placebo were switched to tesamorelin (P-T group, n=111). Methods: Safety included adverse events and glucose parameters. Results: Tesamorelin was generally well tolerated. The prevalence of adverse events and serious adverse events during the extension phase was comparable with the initial phase. Changes in glucose parameters over 52 weeks were not clinically significant and similar to those after 26 weeks. The change in VAT was sustained at -18% over 52 weeks of treatment (P<0.001 versus baseline) as was the change in triglycerides (-51 mg/dl, P < 0.001 versus baseline). Similar sustained beneficial effects were seen for total cholesterol, but high-density lipoprotein decreased minimally over 52 weeks. Upon discontinuation of tesamorelin, VAT reaccumulated. Conclusion: Treatment with tesamorelin was generally well tolerated and resulted in sustained decreases in VAT and triglycerides over 52 weeks without aggravating glucose. Though effects on VAT are sustained during treatment for 52 weeks, these effects do not last beyond the duration of treatment. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Falutz, Julian] McGill Univ, Ctr Hlth, Montreal Gen Hosp, Montreal, PQ, Canada. [Allas, Soraya; Mamputu, Jean-Claude; Potvin, Diane] Theratechnol Inc, Montreal, PQ, Canada. [Kotler, Donald] St Lukes Roosevelt Hosp, New York, NY USA. [Kotler, Donald] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Somero, Michael] Desert Reg Med Ctr, Palm Springs, CA USA. [Berger, Daniel] Northstar Healthcare, Chicago, IL USA. [Brown, Stephen] AIDS Res Alliance, W Hollywood, CA USA. [Fessel, Jeffrey] Kaiser Fdn Res Inst, San Francisco, CA USA. [Turner, Ralph] Phase V Technol Inc, Wellesley Hills, MA USA. [Grinspoon, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grinspoon, Steven] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Grinspoon, S (reprint author), MGH, MGH Program Nutritional Metab, Boston, MA 02493 USA. EM sgrinspoon@Partners.org OI Mamputu, Jean-Claude/0000-0001-8493-959X NR 17 TC 31 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD SEP 12 PY 2008 VL 22 IS 14 BP 1719 EP 1728 DI 10.1097/QAD.0b013e32830a5058 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 353DQ UT WOS:000259546700006 PM 18690162 ER PT J AU Hong, CC Kume, T Peterson, RT AF Hong, Charles C. Kume, Tsutomu Peterson, Randall T. TI Role of crosstalk between phosphatidylinositol 3-kinase and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways in artery-vein specification SO CIRCULATION RESEARCH LA English DT Review DE artery-vein specification; signaling crosstalk; Shh; VEGF; Notch; Fox ID ENDOTHELIAL-GROWTH-FACTOR; EMBRYONIC VASCULAR DEVELOPMENT; VENOUS DIFFERENTIATION; SONIC-HEDGEHOG; NOTCH PATHWAY; GENE-FUNCTION; DORSAL AORTA; YOLK-SAC; VEGF; ZEBRAFISH AB Functional and structural differences between arteries and veins lie at the core of the circulatory system, both in health and disease. Therefore, understanding how artery and vein cell identities are established is a fundamental biological challenge with significant clinical implications. Molecular genetic studies in zebrafish and other vertebrates in the past decade have begun to reveal in detail the complex network of molecular pathways that specify artery and vein cell fates during embryonic development. Recently, a chemical genetic approach has revealed evidence that artery-vein specification is governed by cross talk between phosphoinositide 3-kinase and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in artery-vein specification. We discuss recent findings on the signaling pathways involved in artery-vein specification during zebrafish development and compare and contrast these results to those from mammalian systems. It is anticipated that the complementary approaches of genetics and chemical biology, involving a variety of model organisms and systems, will lead to a better understanding of artery-vein specification and possibly to novel therapeutic approaches to treat vascular diseases. C1 [Hong, Charles C.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Sch Med,Dept Med, Nashville, TN 37232 USA. [Hong, Charles C.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. [Kume, Tsutomu] Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA USA. [Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Charlestown, MA USA. RP Hong, CC (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Sch Med,Dept Med, 383 PRB,2220 Pierce Ave, Nashville, TN 37232 USA. EM charles.c.hong@vanderbilt.edu RI Hong, Charles/C-9989-2010 FU NIH [HL081535, HL074121, HL079267]; GlaxoSmithKline Research & Education Foundation for Cardiovascular Research FX This work was supported by NIH grants HL081535 (to C. C. H.), HL074121 (to T. K.), and HL079267 (to R. T. P.) and a grant from the GlaxoSmithKline Research & Education Foundation for Cardiovascular Research (to C. C. H.). NR 50 TC 32 Z9 35 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP 12 PY 2008 VL 103 IS 6 BP 573 EP 579 DI 10.1161/CIRCRESAHA.108.180745 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 349AZ UT WOS:000259252500007 PM 18796644 ER PT J AU Briggs, LE Takeda, M Cuadra, AE Wakimoto, H Marks, MH Walker, AJ Seki, T Oh, SP Lu, JT Sumners, C Raizada, MK Horikoshi, N Weinberg, EO Yasui, K Ikeda, Y Chien, KR Kasahara, H AF Briggs, Laura E. Takeda, Morihiko Cuadra, Adolfo E. Wakimoto, Hiroko Marks, Melissa H. Walker, Alexandra J. Seki, Tsugio Oh, Suk P. Lu, Jonathan T. Sumners, Colin Raizada, Mohan K. Horikoshi, Nobuo Weinberg, Ellen O. Yasui, Kenji Ikeda, Yasuhiro Chien, Kenneth R. Kasahara, Hideko TI Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects SO CIRCULATION RESEARCH LA English DT Article DE conduction; contraction; gene targeting; transcription ID CARDIAC SODIUM-CHANNEL; CONGENITAL HEART-DISEASE; HOMEOBOX GENE; MOUSE HEART; DILATED CARDIOMYOPATHY; HOMEODOMAIN PROTEIN; EXPRESSION; MUTATIONS; SYSTEM; CA2+ AB Homeobox transcription factor Nkx2-5, highly expressed in heart, is a critical factor during early embryonic cardiac development. In this study, using tamoxifen-inducible Nkx2-5 knockout mice, we demonstrate the role of Nkx2-5 in conduction and contraction in neonates within 4 days after perinatal tamoxifen injection. Conduction defect was accompanied by reduction in ventricular expression of the cardiac voltage-gated Na+ channel pore-forming alpha-subunit (Na(v)1.5-alpha), the largest ion channel in the heart responsive for rapid depolarization of the action potential, which leads to increased intracellular Ca2+ for contraction (conduction-contraction coupling). In addition, expression of ryanodine receptor 2, through which Ca2+ is released from sarcoplasmic reticulum, was substantially reduced in Nkx2-5 knockout mice. These results indicate that Nkx2-5 function is critical not only during cardiac development but also in perinatal hearts, by regulating expression of several important gene products involved in conduction and contraction. C1 [Briggs, Laura E.; Takeda, Morihiko; Cuadra, Adolfo E.; Marks, Melissa H.; Walker, Alexandra J.; Seki, Tsugio; Oh, Suk P.; Sumners, Colin; Raizada, Mohan K.; Kasahara, Hideko] Univ Florida, Coll Med, Dept Physiol & Funct Genom, Gainesville, FL 32610 USA. [Wakimoto, Hiroko] Tokyo Med & Dent Univ, Dept Pediat & Dev Biol, Grad Sch Med, Tokyo, Japan. [Lu, Jonathan T.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. [Horikoshi, Nobuo] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA. [Weinberg, Ellen O.] Boston Univ, Med Ctr, Boston, MA 02215 USA. [Yasui, Kenji] Nagoya Univ, Dept Bioinformat Anal, Environm Med Res Inst, Aichi, Japan. [Ikeda, Yasuhiro] Yamaguchi Univ, Sch Med, Dept Mol Cardiovasc Biol, Ube, Yamaguchi 755, Japan. [Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiol Res Ctr, Boston, MA 02114 USA. RP Kasahara, H (reprint author), Univ Florida, Coll Med, Dept Physiol & Funct Genom, 1600 SW Archer Rd,M-540, Gainesville, FL 32610 USA. EM hkasahar@phys.med.ufl.edu FU American Heart Association National Scientific Development Grant and NIH grant [HL081577] FX This work was supported by an American Heart Association National Scientific Development Grant and NIH grant HL081577 (to H. K.). NR 44 TC 49 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP 12 PY 2008 VL 103 IS 6 BP 580 EP 590 DI 10.1161/CIRCRESAHA.108.171835 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 349AZ UT WOS:000259252500008 PM 18689573 ER PT J AU Kisucka, J Chauhan, AK Patten, IS Yesilaltay, A Neumann, C Van Etten, RA Krieger, M Wagner, DD AF Kisucka, Janka Chauhan, Anil K. Patten, Ian S. Yesilaltay, Ayce Neumann, Carola Van Etten, Richard A. Krieger, Monty Wagner, Denisa D. TI Peroxiredoxin1 prevents excessive endothelial activation and early atherosclerosis SO CIRCULATION RESEARCH LA English DT Article DE inflammation; atherosclerosis; antioxidant enzymes; endothelium; peroxiredoxin ID APOE-DEFICIENT MICE; OXIDATIVE STRESS; INTERFERON-GAMMA; RECEPTOR-GAMMA; NITRIC-OXIDE; P-SELECTIN; IN-VIVO; OXYGEN; CELLS; INFLAMMATION AB The peroxiredoxin (Prdx) family of antioxidant enzymes uses redox-active cysteines to reduce peroxides, lipid hydroperoxides, and peroxynitrites. Prdx1 is known to be important to protect red blood cells against reactive oxygen species and in tumor prevention. In this study, the role of Prdx1 in inflammation, thrombosis, and atherosclerosis was investigated. Using intravital microscopy, we showed that the number of leukocytes rolling per minute in unstimulated veins was increased by 2.5-fold in Prdx1(-/-) compared to Prdx1(-/-) mice. In Prdx1(-/-) mice, 50% of leukocytes rolled at a velocity < 10 mu m/sec compared with 10% in Prdx1(-/-) mice, suggesting that adhesion molecule density on the endothelium may have been increased by Prdx1 deficiency. Indeed, endothelial P-selectin, soluble P-selectin, and von Willebrand factor in plasma were increased in Prdx1(-/-) mice compared to Prdx1(-/-) mice, indicating elevated Weibel-Palade body release. In contrast to this excessive endothelial activation, Prdx1(-/-) platelets showed no sign of hyperreactivity, and their aggregation both in vitro and in vivo was normal. We also examined the role of Prdx1 in the apoE(-/-) murine spontaneous model of atherosclerosis. Prdx1(-/-)/apoE(-/-) mice fed normal chow developed larger, more macrophage-rich aortic sinus lesions than Prdx1(-/-)/apoE(-/-) mice, despite similar amounts and size distributions of cholesterol in their plasma lipoproteins. Thus, Prdx1 protects against excessive endothelial activation and atherosclerosis, and the Prdx1(-/-) mice could serve as an animal model susceptible to chronic inflammation. C1 [Kisucka, Janka; Chauhan, Anil K.; Patten, Ian S.; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Kisucka, Janka; Chauhan, Anil K.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Yesilaltay, Ayce; Krieger, Monty] MIT, Dept Biol, Cambridge, MA 02139 USA. [Neumann, Carola] Med Univ S Carolina, Charleston, SC USA. [Van Etten, Richard A.] Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@idi.harvard.edu FU NIH: National Heart, Lung, and Blood Institute [R37 HL041002, PO1 HL066105]; National Cancer Institute [CA077691] FX This work was supported by the NIH: National Heart, Lung, and Blood Institute grants R37 HL041002 (to D. D. W) and PO1 HL066105 (to D. D. W and M. K.) and National Cancer Institute grant CA077691 (R. A. V.). NR 45 TC 56 Z9 57 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP 12 PY 2008 VL 103 IS 6 BP 598 EP 605 DI 10.1161/CIRCRESAHA.108.174870 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 349AZ UT WOS:000259252500010 PM 18689572 ER PT J AU Hamilton, BJ Wang, XW Collins, J Bloch, D Bergeron, A Henry, B Terry, BM Zan, M Mouland, AJ Rigby, WFC AF Hamilton, B. JoNell Wang, Xiao-Wei Collins, Jane Bloch, Donald Bergeron, Alan Henry, Brian Terry, Benjamin M. Zan, Moe Mouland, Andrew J. Rigby, William F. C. TI Separate cis-trans pathways post-transcriptionally regulate murine CD154 (CD40 ligand) expression - A novel function for CA repeats in the 3 '-untranslated region SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA STABILITY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRACT-BINDING-PROTEIN; TNF-ALPHA; HNRNP-L; RHEUMATOID-ARTHRITIS; RICH ELEMENTS; T-CELLS; POLYADENYLATION; GENE AB We report a role for CA repeats in the 3'-untranslated region (3'-UTR) in regulating CD154 expression. Human CD154 is encoded by an unstable mRNA; this instability is conferred in cis by a portion of its 3'-UTR that includes a polypyrimidine-rich region and CA dinucleotide repeat. We demonstrate similar instability activity with the murine CD154 3'-UTR. This instability element mapped solely to a conserved 100-base CU-rich region alone, which we call a CU-rich response element. Surprisingly, the CA dinucleotide-rich region also regulated reporter expression but at the level of translation. This activity was associated with poly(A) tail shortening and regulated by heterogeneous nuclear ribonucleoprotein L levels. We conclude that the CD154 3'-UTR contains dual cis-acting elements, one of which defines a novel function for exonic CA dinucleotide repeats. These findings suggest a mechanism for the association of 3'-UTR CA-rich response element polymorphisms with CD154 overexpression and the subsequent risk of autoimmune disease. C1 [Hamilton, B. JoNell; Wang, Xiao-Wei; Collins, Jane; Henry, Brian; Zan, Moe; Rigby, William F. C.] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Lebanon, NH 03756 USA. [Hamilton, B. JoNell; Wang, Xiao-Wei; Collins, Jane; Henry, Brian; Zan, Moe; Rigby, William F. C.] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Microbiol & Immunol, Lebanon, NH 03756 USA. [Bloch, Donald] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Bloch, Donald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Terry, Benjamin M.] New York Med Coll, Valhalla, NY 10595 USA. [Mouland, Andrew J.] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. [Mouland, Andrew J.] McGill Univ, Montreal, PQ H3T 1E2, Canada. RP Rigby, WFC (reprint author), Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Lebanon, NH 03756 USA. EM William.Rigby@Dartmouth.edu FU National Institutes of Health [R01AR49834, T32AI07363]; American College of Rheumatology Research and Education Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grant R01AR49834. This work was also supported by a grant from the American College of Rheumatology Research and Education Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact.; Supported as a postdoctoral fellow on National Institutes of Health Training Grant T32AI07363. NR 51 TC 16 Z9 16 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 12 PY 2008 VL 283 IS 37 BP 25606 EP 25616 DI 10.1074/jbc.M802492200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 345QZ UT WOS:000259012700056 PM 18640985 ER PT J AU Hounie, AG Cappi, C Cordeiro, Q Sampaio, AS Moraes, I do Rosario, MC Palacios, SA Goldberg, AC Vallada, HP Machado-Lima, A Nakano, E Kalil, J Pauls, D Pereira, CAB Guilherme, L Miguel, EC AF Hounie, Ana Gabriela Cappi, Carolina Cordeiro, Quirino Sampaio, Aline Santos Moraes, Ivanil do Rosario, Maria Conceicao Palacios, Selma A. Goldberg, Anna Carla Vallada, Homero Pinto Machado-Lima, Ariane Nakano, Eduardo Kalil, Jorge Pauls, David Pereira, Carlos Alberto B. Guilherme, Luiza Miguel, Euripedes Constantino TI TNF-alpha polymorphisms are associated with obsessive-compulsive disorder SO NEUROSCIENCE LETTERS LA English DT Article DE case-control study; cytokine; autoimmune; molecular genetics; rheumatic fever ID NECROSIS-FACTOR-ALPHA; RHEUMATIC HEART-DISEASE; PROMOTER POLYMORPHISMS; FUNCTIONAL-ANALYSIS; SPECTRUM DISORDERS; GENE POLYMORPHISM; GENOMIC ANCESTRY; MEXICAN PATIENTS; FEVER; SCHIZOPHRENIA AB Introduction: Several lines of evidence support an immunologic involvement in obsessive-compulsive disorder (OCD): the increased prevalence of OCD in patients with rheumatic fever (RF), and the aggregation of obsessive-compulsive spectrum disorders among relatives of RF probands. Tumor necrosis factor alpha is a proinflammatory cytokine involved in RF and other autoimmune diseases. Polymorphisms in the promoter region of the TNFA gene have been associated with RE Given the association between OCD and RF, the goal of the present study was to investigate a possible association between polymorphisms within the promoter region of TNFA and OCD. Materials and methods: Two polymorphisms were investigated: -308 G/A and -238 G/A. The allelic and genotypic frequencies of these polymorphisms were examined in 111 patients who fulfilled DSM-IV criteria for OCD and compared with the frequencies in 250 controls. Results: Significant associations were observed between both polymorphisms and OCD. For -238 G/A, an association between the A allele and OCD was observed (X-2 = 12.05, p = 0.0005). A significant association was also observed between the A allele of the -308 G/A polymorphism and OCD (X-2 = 7.09, p = 0.007). Finally, a haplotype consisting of genotypes of these two markers was also examined. Significant association was observed for the A-A haplotype (p = 0.0099 after correcting for multiple testing). Discussion: There is association between the -308 G/A and -238 G/A TNFA polymorphisms and OCD in our Brazilian sample. However, these results need to be replicated in larger samples collected from different populations. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Hounie, Ana Gabriela; Cappi, Carolina; Cordeiro, Quirino; Sampaio, Aline Santos; Moraes, Ivanil; do Rosario, Maria Conceicao; Vallada, Homero Pinto; Machado-Lima, Ariane; Nakano, Eduardo; Miguel, Euripedes Constantino] Univ Sao Paulo, Clin Hosp, Inst Psychiat, Dept Psychiat, BR-05508 Sao Paulo, Brazil. [Palacios, Selma A.; Goldberg, Anna Carla; Kalil, Jorge; Guilherme, Luiza] Univ Sao Paulo, Sch Med, Dept Clin Med, BR-05508 Sao Paulo, Brazil. [Palacios, Selma A.; Goldberg, Anna Carla; Kalil, Jorge; Guilherme, Luiza] Univ Sao Paulo, Sch Med, Heart Inst InCor, BR-05508 Sao Paulo, Brazil. [Pauls, David] Univ Sao Paulo, Dept Math & Stat, BR-05508 Sao Paulo, Brazil. [Pauls, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA USA. [do Rosario, Maria Conceicao] Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. RP Hounie, AG (reprint author), FMUSP, Dept & Inst Psychiat, CEAPESQ, Rua Doutor Ovidio Pires Campos,785 3 Andar,Sala 0, BR-05403010 Sao Paulo, Brazil. EM anah@protoc.com.br RI Miguel, Euripedes/B-2871-2008; Nakano, Eduardo/G-1660-2011; Machado-Lima, Ariane/F-4245-2012; Guglielmi, Luiza/E-7676-2013; SAMPAIO, ALINE/M-1229-2013; Goldberg, Anna Carla/H-8594-2014; Vallada, Homero/D-1333-2014; do Rosario, Maria Conceicao/E-5213-2012 OI Machado-Lima, Ariane/0000-0002-5719-338X; SAMPAIO, ALINE/0000-0001-5568-6167; Goldberg, Anna Carla/0000-0003-2600-7940; Vallada, Homero/0000-0001-5123-8295; do Rosario, Maria Conceicao/0000-0002-9687-0072 FU CAPES/PRODOC, FAPESP [98/15-013-9, 2005/55628-8]; CNPq FX This work was supported by grants from CAPES/PRODOC, FAPESP (grants 98/15-013-9 and 2005/55628-8), and CNPq. We thank Maria Alice and Maria Eugenia De Mathis, Juliana B Diniz, Pedro G Alvarenga, Andre A Seixas, Fernando Akkerman, Marcos S Vasconcelos, Maria C Bravo, Priscila Chacon, Sergio Broto, Yara Garzuzi, Rosemar Prota and Daniela Dourado for conducting the clinical evaluations. We also thank Maria Lucia Carnevale Marin, Lea Oliveira, Kellen Fae and Gabriel Victora for helping in the genotyping. We also thank Dr. Rajendranath Ramasawmy for his help and support. NR 53 TC 26 Z9 28 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 12 PY 2008 VL 442 IS 2 BP 86 EP 90 DI 10.1016/j.neulet.2008.07.022 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 344EP UT WOS:000258909500002 PM 18639610 ER PT J AU Makarova, A Bercury, KK Adams, KW Joyner, D Deng, MH Spoelgen, R Koker, M Strickland, DK Hyman, BT AF Makarova, Alexandra Bercury, Kathryn K. Adams, Kenneth W. Joyner, Daniel Deng, Meihua Spoelgen, Robert Koker, Mirjam Strickland, Dudley K. Hyman, Bradley T. TI The LDL receptor-related protein can form homo-dimers in neuronal cells SO NEUROSCIENCE LETTERS LA English DT Article DE LRP; low density lipoprotein receptor-related; protein; dimer; homo-dimerization ID LIFETIME IMAGING MICROSCOPY; AMYLOID PRECURSOR PROTEIN; METHYL-D-ASPARTATE; FLUORESCENCE COMPLEMENTATION; INTRACELLULAR DOMAIN; APOPTOTIC CELLS; DENSITY; LRP; ADAPTER; PHOSPHORYLATION AB The ability of the low density lipoprotein receptor-related protein (LRP) to form homo-dimers was studied in mouse neuroblastoma and human neuroglioma cells as well as in primary cortical cultures from adult mouse brain. Homo-dimerization of LRP light chain (LC) was shown by several methods including co-immunoprecipitation, fluorescence lifetime imaging microscopy, and bimolecular fluorescence complementation assay. The requirement of intact NPXY motifs of LRP LC for homo-dimerization was ruled out by co-immunoprecipitation assay. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Alzheimer Unit, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA. [Strickland, Dudley K.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Alzheimer Unit, MassGen Inst Neurodegenerat Dis,Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org FU NIH AG [12406] FX Supported by NIH AG 12406. NR 26 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 12 PY 2008 VL 442 IS 2 BP 91 EP 95 DI 10.1016/j.neulet.2008.06.070 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 344EP UT WOS:000258909500003 PM 18602448 ER PT J AU White, RM Zon, LI AF White, Richard Mark Zon, Leonard I. TI Melanocytes in development, regeneration, and cancer SO CELL STEM CELL LA English DT Review ID NEURAL CREST DEVELOPMENT; PRIMARY MELANOMA PROGRESSION; RECEPTOR TYROSINE KINASE; ENDOTHELIN-B RECEPTOR; C-KIT PROTOONCOGENE; TRANSCRIPTION FACTOR; STEM-CELLS; METASTATIC MELANOMA; IN-VITRO; DOPACHROME-TAUTOMERASE AB The genes required for stem cell specification and lineage restriction during embryogenesis also play fundamental roles in adult tissue regeneration and cancer. This "development-regeneration-cancer" axis is exemplified by the vertebrate pigmentation system. Melanocytes exhibit almost unlimited self-renewal capacity during regenerative processes such as mammalian hair recoloration and zebrafish fin regeneration. Melanoma utilizes many regulatory signals and pathways required during ontogeny and regeneration. A discussion of these interconnections highlights how studies of stem cell function in embryonic and regenerative contexts can yield insights into melanoma biology. C1 [White, Richard Mark; Zon, Leonard I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [White, Richard Mark; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Div Hematol Oncol, Boston, MA 02115 USA. [White, Richard Mark; Zon, Leonard I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zon, LI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu NR 95 TC 65 Z9 67 U1 0 U2 5 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 SEP 11 PY 2008 VL 3 IS 3 BP 242 EP 252 DI 10.1016/j.stem.2008.08.005 PG 11 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 354UR UT WOS:000259665000008 PM 18786412 ER PT J AU Mercher, T Cornejo, MG Sears, C Kindler, T Moore, SA Maillard, I Pear, WS Aster, JC Gilliland, DG AF Mercher, Thomas Cornejo, Melanie G. Sears, Christopher Kindler, Thomas Moore, Sandra A. Maillard, Ivan Pear, Warren S. Aster, Jon C. Gilliland, D. Gary TI Notch signaling specifies megakaryocyte development from hematopoietic stem cells SO CELL STEM CELL LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TRANSCRIPTION FACTOR GATA-1; ZINC-FINGER PROTEIN; T-CELL; BONE-MARROW; LINEAGE COMMITMENT; SELF-RENEWAL; IN-VITRO; B-CELL; DIFFERENTIATION AB In the hematopoietic system, Notch signaling specifies T cell lineage fate, in part through negative regulation of B cell and myeloid lineage development. However, we unexpectedly observed the development of megakaryocytes when using heterotypic cocultures of hematopoetic stem cells with OP9 cells expressing Delta-like1, but not with parental OP9 cells. This effect was abrogated by inhibition of Notch signaling either with gamma-secretase inhibitors or by expression of the dominant-negative Mastermind-like1. The importance of Notch signaling for megakaryopoietic development in vivo was confirmed by using mutant alleles that either activate or inhibit Notch signaling. These findings indicate that Notch is a positive regulator of megakaryopoiesis and plays a more complex role in cell-fate decisions among myeloid progenitors than previously appreciated. C1 [Mercher, Thomas; Cornejo, Melanie G.; Kindler, Thomas; Moore, Sandra A.; Gilliland, D. Gary] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 20115 USA. [Aster, Jon C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Pathol, Boston, MA 02115 USA. [Sears, Christopher] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Maillard, Ivan] Univ Michigan, Dept Med, Inst Life Sci, Ann Arbor, MI 48104 USA. [Maillard, Ivan] Univ Michigan, Div Hematol Oncol, Ctr Stem Cell Biol, Ann Arbor, MI 48104 USA. [Pear, Warren S.] Univ Penn, Dept Pathol & Lab Med, Div Hematol, Abramson Family Res Inst, Philadelphia, PA 19104 USA. [Gilliland, D. Gary] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Mercher, T (reprint author), Hop Necker Enfants Malad, INSERM, EMI0210, 149 Rue Sevres, F-75743 Paris 15, France. EM tmercher@rics.bwh.harvard.edu; ggilliland@rics.bwh.harvard.edu RI Kindler, Thomas/K-5995-2013; Mercher, Thomas/J-2446-2014 OI Mercher, Thomas/0000-0003-1552-087X FU National Institute of Health [AI047833, CA119070, DK50654, CA66996]; Leukemia and Lymphoma Society FX We are very grateful to Dr. J.C. Zuniga-Pflucker for the OP9-GFP and OP9-DL1 cells; Dr. C. Lavau for the ICN1, Hesl, and Hes5 constructs; and Dr. J.D. Griffin and Dr. Lizi Wu for the dnMAML1 construct. We are very grateful to Dr. O. Shestova and Dr. M. Santos for help with dnMAML1 transgenics. We thank A. Fabian for technical assistance with cell sorting and Dr. J.L. Kutok and the Dana Farber Histopathology Core Facility for histology studies. T.M. is a recipient of a Leukemia and Lymphoma Society Special Fellow Award. D.G.G. is a Doris Duke Foundation Distinguished Clinical Scientist and a Howard Hughes Medical Institute investigator. This work was supported in part by National Institute of Health grants AI047833 (W.S.P.), CA119070 (J.C.A.), and DK50654 and CA66996 (D.G.G.) and by the Leukemia and Lymphoma Society to W.S.P., J.C.A., and D.G.G. The authors declare no competing financial interests. NR 50 TC 76 Z9 78 U1 8 U2 22 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 SEP 11 PY 2008 VL 3 IS 3 BP 314 EP 326 DI 10.1016/j.stem.2008.07.010 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 354UR UT WOS:000259665000014 PM 18786418 ER PT J AU Maherali, N Ahfeldt, T Rigamonti, A Utikal, J Cowan, C Hochedlinger, K AF Maherali, Nimet Ahfeldt, Tim Rigamonti, Alessandra Utikal, Jochen Cowan, Chad Hochedlinger, Konrad TI A high-efficiency system for the generation and study of human induced pluripotent stem cells SO CELL STEM CELL LA English DT Article ID HUMAN SOMATIC-CELLS; DEFINED FACTORS; FIBROBLASTS; MOUSE; DIFFERENTIATION; EXPRESSION; INDUCTION; LINES AB Direct reprogramming of human fibroblasts to a pluripotent state has been achieved through ectopic expression of the transcription factors OCT4, SOX2, and either cMYC and KLF4 or NANOG and LIN28. Little is known, however, about the mechanisms by which reprogramming occurs, which is in part limited by the low efficiency of conversion. To this end, we sought to create a doxycycline-inclucible lentiviral system to convert primary human fibroblasts and keratinocytes into human induced pluripotent stem cells (hiPSCs). hiPSCs generated with this system were molecularly and functionally similar to human embryonic stem cells (hESCs), demonstrated by gene expression profiles, DNA methylation status, and differentiation potential. While expression of the viral transgenes was required for several weeks in fibroblasts, we found that 10 days was sufficient for the reprogramming of keratinocytes. Using our inducible system, we developed a strategy to induce hiPSC formation at high frequency. Upon addition of doxycycline to hiPSC-derived differentiated cells, we obtained "secondary" hiPSCs at a frequency at least 100-fold greater than the initial conversion. The ability to reprogram cells at high efficiency provides a unique platform to dissect the underlying molecular and biochemical processes that accompany nuclear reprogramming. C1 [Maherali, Nimet; Ahfeldt, Tim; Rigamonti, Alessandra; Utikal, Jochen; Cowan, Chad; Hochedlinger, Konrad] Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. [Maherali, Nimet; Utikal, Jochen; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Cowan, Chad] Stowers Med Inst, Boston, MA 02114 USA. [Maherali, Nimet] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Ahfeldt, Tim] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Biol Mol Cell Biol 2, D-20246 Hamburg, Germany. RP Cowan, C (reprint author), Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. EM ccowan1@partners.org; khochedlinger@helix.mgh.harvard.edu RI Ahfeldt, Tim/E-2935-2017; OI Utikal, Jochen/0000-0001-5316-0241 FU Natural Sciences and Engineering Research Council of Canada; Dr. Mildred Scheel Foundation for Cancer Research; Harvard Stem Cell Institute; Stowers Institute for Medical Research; National Institutes of Health (NIH); Kimmel Foundation; V Foundation FX We thank the Stowers Institute for Medical Research Microarray Group, Christopher Seidel, and Reddy Gali (Harvard FAS Life Sciences Research Computing) for assistance with transcriptional profiling and analysis; Jennifer Shay for technical assistance; and Matthias Stadtfeld and Jose Polo for critical reading of the manuscript. N.M. is supported by a graduate scholarship from the Natural Sciences and Engineering Research Council of Canada and a Sir James Lougheed Award from Alberta Scholarships. J.U. is supported by the Dr. Mildred Scheel Foundation for Cancer Research. C.C. is supported by the Harvard Stem Cell Institute and the Stowers Institute for Medical Research. K.H. is supported by a National Institutes of Health (NIH) Director's Innovator Award, the Harvard Stem Cell Institute, the Kimmel Foundation, and the V Foundation. NR 20 TC 301 Z9 326 U1 1 U2 28 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 SEP 11 PY 2008 VL 3 IS 3 BP 340 EP 345 DI 10.1016/j.stem.2008.08.003 PG 6 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 354UR UT WOS:000259665000016 PM 18786420 ER PT J AU Stone, JL O'Donovan, MC Gurling, H Kirov, GK Blackwood, DHR Corvin, A Craddock, NJ Gill, M Hultman, CM Lichtenstein, P McQuillin, A Pato, CN Ruderfer, DM Owen, MJ St Clair, D Sullivan, PF Sklar, P Purcell, SM Scolnick, EM Holmans, PA Georgieva, L Nikolov, I Norton, N Williams, H Williams, NM Toncheva, D Milanova, V Thelander, EF Morris, DW O'Dushlaine, CT Kenny, E Waddington, JL Choudhury, K Datta, S Pimm, J Thirumalai, S Puri, V Krasucki, R Lawrence, J Quested, D Bass, N Curtis, D Crombie, C Fraser, G Kwan, SL Muir, WJ McGhee, KA Pickard, B Malloy, P Maclean, AW Van Beck, M Visscher, PM Macgregor, S Pato, MT Medeiros, H Middleton, F Carvalho, C Morley, C Fanous, A Conti, D Knowles, JA Ferreira, CP Azevedo, MH McCarroll, SA Gates, C Daly, MJ Sklar, P AF Stone, Jennifer L. O'Donovan, Michael C. Gurling, Hugh Kirov, George K. Blackwood, Douglas H. R. Corvin, Aiden Craddock, Nick J. Gill, Michael Hultman, Christina M. Lichtenstein, Paul McQuillin, Andrew Pato, Carlos N. Ruderfer, Douglas M. Owen, Michael J. St Clair, David Sullivan, Patrick F. Sklar, Pamela Purcell, Shaun M. Scolnick, E. M. Holmans, P. A. Georgieva, L. Nikolov, I. Norton, N. Williams, H. Williams, N. M. Toncheva, D. Milanova, V. Thelander, E. F. Morris, D. W. O'Dushlaine, C. T. Kenny, E. Waddington, J. L. Choudhury, K. Datta, S. Pimm, J. Thirumalai, S. Puri, V. Krasucki, R. Lawrence, J. Quested, D. Bass, N. Curtis, D. Crombie, C. Fraser, G. Kwan, S. L. Muir, W. J. McGhee, K. A. Pickard, B. Malloy, P. Maclean, A. W. Van Beck, M. Visscher, P. M. Macgregor, S. Pato, M. T. Medeiros, H. Middleton, F. Carvalho, C. Morley, C. Fanous, A. Conti, D. Knowles, J. A. Ferreira, C. P. Azevedo, M. H. McCarroll, S. A. Gates, C. Daly, M. J. Sklar, P. CA Int Schizophrenia Consortium TI Rare chromosomal deletions and duplications increase risk of schizophrenia SO NATURE LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; LOW COPY REPEATS; DISORDERS; REARRANGEMENTS; ASSOCIATION; LINKAGE; NUMBER; LOCUS; MICRODELETION; ARCHITECTURE AB Schizophrenia is a severe mental disorder marked by hallucinations, delusions, cognitive deficits and apathy, with a heritability estimated at 73 - 90% ( ref. 1). Inheritance patterns are complex, and the number and type of genetic variants involved are not understood. Copy number variants ( CNVs) have been identified in individual patients with schizophrenia(2-7) and also in neurodevelopmental disorders(8-11), but large- scale genome- wide surveys have not been performed. Here we report a genome- wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls, using high- density microarrays. For CNVs that were observed in less than 1% of the sample and were more than 100 kilobases in length, the total burden is increased 1.15- fold in patients with schizophrenia in comparison with controls. This effect was more pronounced for rarer, single- occurrence CNVs and for those that involved genes as opposed to those that did not. As expected, deletions were found within the region critical for velo- cardio- facial syndrome, which includes psychotic symptoms in 30% of patients(12). Associations with schizophrenia were also found for large deletions on chromosome 15q13.3 and 1q21.1. These associations have not previously been reported, and they remained significant after genome- wide correction. Our results provide strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome- wide and at specific loci. C1 [Stone, Jennifer L.; Ruderfer, Douglas M.; Sklar, Pamela; Purcell, Shaun M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Stone, Jennifer L.; Ruderfer, Douglas M.; Sklar, Pamela; Purcell, Shaun M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Stone, Jennifer L.; Ruderfer, Douglas M.; Sklar, Pamela; Purcell, Shaun M.; Scolnick, E. M.; McCarroll, S. A.; Gates, C.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Stone, Jennifer L.; Ruderfer, Douglas M.; Sklar, Pamela; Purcell, Shaun M.; McCarroll, S. A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Cambridge, MA 02142 USA. [O'Donovan, Michael C.; Kirov, George K.; Craddock, Nick J.; Owen, Michael J.; Holmans, P. A.; Georgieva, L.; Nikolov, I.; Norton, N.; Williams, H.; Williams, N. M.] Cardiff Univ, Sch Med, Dept Med Psychol, Sch Med, Cardiff C14 4XN, Wales. [Gurling, Hugh; McQuillin, Andrew; Choudhury, K.; Datta, S.; Pimm, J.; Puri, V.; Krasucki, R.; Lawrence, J.; Bass, N.] UCL, Sch Med, Mol Psychiat Lab, Dept Mental Hlth Sci,Windeyer Inst Med Sci, London W1T 4JF, England. [Blackwood, Douglas H. R.; Muir, W. J.; McGhee, K. A.; Pickard, B.; Malloy, P.; Maclean, A. W.; Van Beck, M.] Univ Edinburgh, Div Psychiat, Sch Mol & Clin Med, Edinburgh EH10 5HF, Midlothian, Scotland. [Corvin, Aiden; Gill, Michael; Morris, D. W.; O'Dushlaine, C. T.; Kenny, E.] Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dept Psychiat, Dublin 2, Ireland. [Corvin, Aiden; Gill, Michael; Morris, D. W.; O'Dushlaine, C. T.; Kenny, E.] Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Inst Mol Med, Dublin 2, Ireland. [Hultman, Christina M.; Lichtenstein, Paul; Thelander, E. F.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Hultman, Christina M.] Uppsala Univ, Dept Neurosci Psychiat, SE-75017 Uppsala, Sweden. [Pato, Carlos N.; Pato, M. T.; Medeiros, H.; Carvalho, C.; Fanous, A.; Conti, D.; Knowles, J. A.] Univ So Calif, Ctr Genom Psychiat, Los Angeles, CA 90033 USA. [St Clair, David; Kwan, S. L.] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Visscher, P. M.; Macgregor, S.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Toncheva, D.] Univ Hosp Maichin Dom, Dept Med Genet, Sofia 1431, Bulgaria. [Milanova, V.] Alexander Univ Hosp, Dept Psychiat, Psychiat Clin 1, Sofia 1431, Bulgaria. [Waddington, J. L.] Royal Coll Surgeons Ireland, Molec & Cellular Therapeut & RCSI res Inst, Dublin 2, Ireland. [Thirumalai, S.] W Berkshire NHS Trust, Reading RG3 5LR, Berks, England. [Quested, D.] W London Mental Hlth Trust, Hammersmith & Fulham Mental Hlth Unit, London W6 8RF, England. St Bernards Hosp, London, England. [Curtis, D.] Royal London Hosp, Univ London & E London & City Mental Hlth Trust, Quenn Mary Coll, London E1 1BB, England. [Crombie, C.; Fraser, G.] Univ Aberdeen, Dept Mental Hlth, Aberdeen AB25 2ZD, Scotland. Ravenscraig Hosp, Greenock PA16 9HA, Scotland. [Middleton, F.; Morley, C.] SUNY, Upstate Med Ctr, Syracuse, NY 13210 USA. [Fanous, A.] Washington VA Med Ctr, Washington, DC 20422 USA. [Fanous, A.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC 20057 USA. [Fanous, A.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA. [Ferreira, C. P.; Azevedo, M. H.] Dept Psychiat, P-9500310 Sao Miguel, Portugal. Univ Coimbra, Dept Psychiat, P-3004504 Coimbra, Portugal. RP Sklar, P (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA. EM sklar@chgr.mgh.harvard.edu RI Morley, Christopher P/K-1907-2014; macedo santos, antonio/M-5737-2013; Pickard, Benjamin/K-3923-2014; Holmans, Peter/F-4518-2015; Ruderfer, Douglas/M-5795-2016; Macgregor, Stuart/C-6442-2009; turton, miranda/F-4682-2011; Gurling, Hugh/A-5029-2010 OI Morris, Derek/0000-0002-3413-570X; Morley, Christopher P/0000-0003-0185-7148; Gill, Michael/0000-0003-0206-5337; lichtenstein, paul/0000-0003-3037-5287; McQuillin, Andrew/0000-0003-1567-2240; Visscher, Peter/0000-0002-2143-8760; macedo santos, antonio/0000-0003-2180-2718; Pickard, Benjamin/0000-0002-2374-6329; Holmans, Peter/0000-0003-0870-9412; Ruderfer, Douglas/0000-0002-2365-386X; de Oliveira Barreto Coimbra Carvalho, Celia Maria/0000-0003-4453-8139; Corvin, Aiden/0000-0001-6717-4089; O'Donovan, Michael/0000-0001-7073-2379; Macgregor, Stuart/0000-0001-6731-8142; FU Medical Research Council (UK) Programme; National Institutes of Mental Health (USA) [CONTE: 2 P50 MH066392-05A1]; Swedish Council for Working Life and Social Research [FO 184/2000; 2001-2368]; Stanley Medical Research Institute [MH071681]; Narsad Young Investigator Award; Australian National Health and Medical Research Council; Science Foundation Ireland; Health Research Board (Ireland); Stanley Medical Research Institute; Wellcome Trust; GlaxoSmithKline; Generation Scotland; Genetics Health Initiative; Neuroscience Research Charitable Trust; Camden and Islington Mental Health and Social Care Trust; East London and City Mental Heath Trust; West Berkshire NHS Trust,; West London Mental Health Trust; Oxfordshire and Buckinghamshire Mental Health Partnership NHS Trust; South Essex Partnership NHS Foundation Trust; Gloucestershire Partnership NHS Foundation Trust; Mersey Care NHS Trust; Hampshire Partnership NHS Trust; North East London Mental Health Trust; Chief Scientist Office of the Scottish Executive; Sylvan C. Herman Foundation; National Institutes of Mental Health and the Department of Veterans Affairs; [MH074027]; [MH077139]; [MH080403] FX We thank the patients and families who contributed their time and DNA to these studies, and also D. Altshuler and members of the Medical and Population Genetics group at the Broad Institute of Harvard and Massachusetts Institute of Technology for valuable discussion. The group at the Stanley Center for Psychiatric Research at the Broad Institute was supported by the Stanley Medical Research Institute (E.M.S.), the Sylvan C. Herman Foundation (E.M.S.), and MH071681 (P.S.). The Cardiff University group was supported by a Medical Research Council (UK) Programme grant and the National Institutes of Mental Health (USA) (CONTE: 2 P50 MH066392-05A1). The group at Karolinska Institutet was supported by the Swedish Council for Working Life and Social Research (FO 184/2000; 2001-2368). The Massachusetts General Hospital group was supported by the Stanley Medical Research Institute (P.S.), MH071681 (P.S.) and a Narsad Young Investigator Award (S.P.). The group at the Queensland Institute of Medical Research was supported by the Australian National Health and Medical Research Council. The Trinity College Dublin group was supported by Science Foundation Ireland, the Health Research Board (Ireland), the Stanley Medical Research Institute and the Wellcome Trust; Irish controls were supplied by J. McPartlin from the Trinity College Biobank. The work at the University of Aberdeen was partly funded by GlaxoSmithKline and Generation Scotland, Genetics Health Initiative. The University College London clinical and control samples were collected with support from the Neuroscience Research Charitable Trust, the Camden and Islington Mental Health and Social Care Trust, East London and City Mental Heath Trust, the West Berkshire NHS Trust, the West London Mental Health Trust, Oxfordshire and Buckinghamshire Mental Health Partnership NHS Trust, South Essex Partnership NHS Foundation Trust, Gloucestershire Partnership NHS Foundation Trust, Mersey Care NHS Trust, Hampshire Partnership NHS Trust and the North East London Mental Health Trust. The collection of the University of Edinburgh cohort was supported by grants from the Wellcome Trust, London, and the Chief Scientist Office of the Scottish Executive. The group at the University of North Carolina, Chapel Hill, was supported by MH074027, MH077139 and MH080403, the Sylvan C. Herman Foundation (P.F.S.) and the Stanley Medical Research Institute (P.F.S.) The group at the University of Southern California thanks the patients and their families for their collaboration, and acknowledges the support of the National Institutes of Mental Health and the Department of Veterans Affairs. NR 31 TC 783 Z9 802 U1 11 U2 79 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 11 PY 2008 VL 455 IS 7210 BP 237 EP 241 DI 10.1038/nature07239 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 346SZ UT WOS:000259090800050 ER PT J AU Krishnan, MN Ng, A Sukumaran, B Gilfoy, FD Uchil, PD Sultana, H Brass, AL Adametz, R Tsui, M Qian, F Montgomery, RR Lev, S Mason, PW Koski, RA Elledge, SJ Xavier, RJ Agaisse, H Fikrig, E AF Krishnan, Manoj N. Ng, Aylwin Sukumaran, Bindu Gilfoy, Felicia D. Uchil, Pradeep D. Sultana, Hameeda Brass, Abraham L. Adametz, Rachel Tsui, Melody Qian, Feng Montgomery, Ruth R. Lev, Sima Mason, Peter W. Koski, Raymond A. Elledge, Stephen J. Xavier, Ramnik J. Agaisse, Herve Fikrig, Erol TI RNA interference screen for human genes associated with West Nile virus infection SO NATURE LA English DT Article ID DENGUE-VIRUS; INTERACTION NETWORK; VIRAL SPREAD; HOST-CELLS; PROTEIN; ENTRY; REPLICATION; DATABASE; IDENTIFICATION; ENDOCYTOSIS AB West Nile virus ( WNV), and related flaviviruses such as tick- borne encephalitis, Japanese encephalitis, yellow fever and dengue viruses, constitute a significant global human health problem(1). However, our understanding of the molecular interaction of such flaviviruses with mammalian host cells is limited(1). WNV encodes only 10 proteins, implying that it may use many cellular proteins for infection(1). WNV enters the cytoplasm through pH- dependent endocytosis, undergoes cycles of translation and replication, assembles progeny virions in association with endoplasmic reticulum, and exits along the secretory pathway(1-3). RNA interference ( RNAi) presents a powerful forward genetics approach to dissect virus - host cell interactions(4-6). Here we report the identification of 305 host proteins that affect WNV infection, using a human- genome-wide RNAi screen. Functional clustering of the genes revealed a complex dependence of this virus on host cell physiology, requiring a wide variety of molecules and cellular pathways for successful infection. We further demonstrate a requirement for the ubiquitin ligase CBLL1 in WNV internalization, a post- entry role for the endoplasmic- reticulum- associated degradation pathway in viral infection, and the monocarboxylic acid transporter MCT4 as a viral replication resistance factor. By extending this study to dengue virus, we show that flaviviruses have both overlapping and unique interaction strategies with host cells. This study provides a comprehensive molecular portrait of WNV - human cell interactions that forms a model for understanding single plus- stranded RNA virus infection, and reveals potential antiviral targets. C1 [Krishnan, Manoj N.; Sukumaran, Bindu; Sultana, Hameeda; Fikrig, Erol] Yale Univ, Sch Med, Infect Dis Sect, Dept Internal Med, New Haven, CT 06520 USA. [Qian, Feng; Montgomery, Ruth R.] Yale Univ, Sch Med, Rheumatol Sect, Dept Internal Med, New Haven, CT 06520 USA. [Uchil, Pradeep D.; Adametz, Rachel; Agaisse, Herve] Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06520 USA. [Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Gilfoy, Felicia D.; Mason, Peter W.] Univ Texas Galveston, Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Tsui, Melody] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Syst Biol, Boston, MA 02115 USA. [Brass, Abraham L.; Elledge, Stephen J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Genet,Ctr Genet & Genom, Boston, MA 02115 USA. [Lev, Sima] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. [Koski, Raymond A.] L2 Diagnost, New Haven, CT 06511 USA. [Elledge, Stephen J.; Fikrig, Erol] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Fikrig, E (reprint author), Yale Univ, Sch Med, Infect Dis Sect, Dept Internal Med, 333 Cedar St, New Haven, CT 06520 USA. EM erol.fikrig@yale.edu RI Qian, Feng/F-8186-2010; OI Montgomery, Ruth/0000-0002-8661-4454 FU New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease [U54AI057159]; NIH [AI062773, U54 AI057156]; Crohn's and Colitis Foundation of America; CCIB development funds; Emerging and Tropical Infectious Diseases [AI07526]; NIAID FX The human genome RNAi library wasmade available through the support of the New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease (U54AI057159). The screening was performed at the ICCB-Longwood screening facility (Harvard Medical School). We thank B. Lindenbach for suggestions and Y. Benita for illustrations. We thank L2 Diagnostics for providing the anti-WNV antibody. This work was supported by the NIH. A.N. is supported by a fellowship award from the Crohn's and Colitis Foundation of America. R.J.X. is supported by the NIH (AI062773) and by CCIB development funds. F.D.G was supported by an NIH training grant in Emerging and Tropical Infectious Diseases (AI07526); portions of this work were supported by a grant from NIAID to P.W.M. through the WRCE ( NIH U54 AI057156). E. F. and S.J.E. are Investigators of the Howard Hughes Medical Institute. NR 34 TC 306 Z9 312 U1 4 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 11 PY 2008 VL 455 IS 7210 BP 242 EP U67 DI 10.1038/nature07207 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 346SZ UT WOS:000259090800051 PM 18690214 ER PT J AU Goldfine, AB AF Goldfine, Allison B. TI Assessing the cardiovascular safety of diabetes therapies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID OUTCOMES C1 [Goldfine, Allison B.] Joslin Diabet Ctr, Sect Clin Res, Boston, MA 02215 USA. [Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Sect Clin Res, Boston, MA 02215 USA. NR 5 TC 58 Z9 59 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 SEP 11 PY 2008 VL 359 IS 11 BP 1092 EP 1095 DI 10.1056/NEJMp0805758 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 346ON UT WOS:000259078200004 PM 18784098 ER PT J AU Haddad, RI Shin, DM AF Haddad, Robert I. Shin, Dong M. TI Recent advances in head and neck cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR-RECEPTOR; MODULATED RADIATION-THERAPY; UPPER AERODIGESTIVE TRACT; DEPENDENT PROTEIN-KINASE; LYMPH-NODE METASTASIS; LOCALLY ADVANCED HEAD; MULTICENTER PHASE-II; HUMAN-PAPILLOMAVIRUS; OROPHARYNGEAL CARCINOMA C1 [Haddad, Robert I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Haddad, Robert I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Haddad, Robert I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Shin, Dong M.] Emory Univ, Dept Hematol Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. RP Haddad, RI (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM robert_haddad@dfci.harvard.edu RI Ray, Dana/C-3470-2013 FU ImClone Systems; Bristol-Myers Squibb; Sanofi-Aventis FX Dr. Haddad reports receiving consulting fees from ImClone Systems and Bristol-Myers Squibb and lecture fees from Sanofi-Aventis and Bristol-Myers Squibb; and Dr. Shin, lecture fees from Bristol-Myers Squibb and Sanofi-Aventis. No other potential conflict of interest relevant to this article was reported. We thank Drs. Anthea Hammond and Souheil El-Chemaly for their critical reading of and assistance with the preparation of the manuscript. NR 90 TC 411 Z9 423 U1 6 U2 31 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 SEP 11 PY 2008 VL 359 IS 11 BP 1143 EP 1154 DI 10.1056/NEJMra0707975 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 346ON UT WOS:000259078200010 PM 18784104 ER PT J AU Staley, KJ Sims, KB Grant, PE Hedley-Whyte, ET Barnett, SM Rosenberg, ES Caviness, VS Aurora, S AF Staley, Kevin J. Sims, Katherine B. Grant, P. Ellen Hedley-Whyte, E. Tessa Barnett, Sarah M. Rosenberg, Eric S. Caviness, Verne S., Jr. Aurora, Sanjay TI An infant with congenital deafness, lethargy, and hypothermia - Leigh's syndrome, intraventricular hemorrhage, and periventricular leukomalacia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COMPLEX-I DEFICIENCY; ACUTE NECROTIZING ENCEPHALOPATHY; MITOCHONDRIAL ENCEPHALOPATHY; OXIDATIVE-PHOSPHORYLATION; BACTERIAL-MENINGITIS; DISEASE; MUTATIONS; DISORDERS; CHILDREN; SUBUNIT C1 [Staley, Kevin J.; Sims, Katherine B.] Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02114 USA. [Grant, P. Ellen] Massachusetts Gen Hosp, Dept Radiol, Div Pediat, Boston, MA 02114 USA. [Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. [Staley, Kevin J.; Sims, Katherine B.] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Grant, P. Ellen] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Staley, KJ (reprint author), Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02114 USA. NR 42 TC 1 Z9 1 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 SEP 11 PY 2008 VL 359 IS 11 BP 1156 EP 1167 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 346ON UT WOS:000259078200013 PM 18784106 ER PT J AU Hochberg, LR AF Hochberg, Leigh R. TI Turning thought into action SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CORTICAL CONTROL; DEVICES; ARM C1 [Hochberg, Leigh R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hochberg, Leigh R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hochberg, Leigh R.] Dept Vet Affairs Rehabil Res & Dev Serv, Providence, RI USA. [Hochberg, Leigh R.] Brown Univ, Providence, RI 02912 USA. RP Hochberg, LR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Hochberg, Leigh/0000-0003-0261-2273 NR 6 TC 6 Z9 7 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 SEP 11 PY 2008 VL 359 IS 11 BP 1175 EP 1177 DI 10.1056/NEJMcibr0805122 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 346ON UT WOS:000259078200016 PM 18784110 ER PT J AU Hanashiro, K Kanai, M Geng, Y Sicinski, P Fukasawa, K AF Hanashiro, K. Kanai, M. Geng, Y. Sicinski, P. Fukasawa, K. TI Roles of cyclins A and E in induction of centrosome amplification in p53-compromised cells SO ONCOGENE LA English DT Article DE centrosome; cyclin A; cyclin E; CDK2; p53; centrosome amplification ID CHROMOSOME INSTABILITY; E OVEREXPRESSION; DNA-SYNTHESIS; P53 MUTATION; CANCER; DUPLICATION; HYPERAMPLIFICATION; ACTIVATION; EXPRESSION; EXPOSURE AB Abnormal amplification of centrosomes, which occurs frequently in cancers, leads to high frequencies of mitotic defect and chromosome segregation error, profoundly affecting the rate of tumor progression. Centrosome amplification results primarily from overduplication of centrosomes, and p53 is involved in the regulation of centrosome duplication partly through controlling the activity of cyclin-dependent kinase (CDK) 2-cyclin E, a kinase complex critical for the initiation of centrosome duplication. Thus, loss or mutational inactivation of p53 leads to an increased frequency of centrosome amplification. Moreover, the status of cyclin E greatly influences the frequency of centrosome amplification in cells lacking functional p53. Here, we dissected the roles of CDK2-associating cyclins, namely cyclins E and A, in centrosome amplification in the p53-negative cells. We found that loss of cyclin E was readily compensated by cyclin A for triggering the initiation of centrosome duplication, and thus the centrosome duplication kinetics was not significantly altered in cyclin E-deficient cells. It has been shown that cells lacking functional p53, when arrested in either early S-phase or late G(2) phase, continue to reduplicate centrosomes, resulting in centrosome amplification. In cells arrested in early S phase, cyclin E, but not cyclin A, is important in centrosome amplification, whereas in the absence of cyclin E, cyclin A is important for centrosome amplification. In late G(2)-arrested cells, cyclin A is important in centrosome amplification irrespective of the cyclin E status. These findings advance our understandings of the mechanisms underlying the numeral abnormality of centrosomes and consequential genomic instability associated with loss of p53 function and aberrant expression of cyclins E and A in cancer cells. C1 [Hanashiro, K.; Kanai, M.; Fukasawa, K.] H Lee Moffitt Canc Ctr & Res Inst, Mol Oncol Program, Tampa, FL 33612 USA. [Geng, Y.; Sicinski, P.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Geng, Y.; Sicinski, P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Fukasawa, K (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Mol Oncol Program, 12902 Magnolia Dr,SRB-2, Tampa, FL 33612 USA. EM kenji.fukasawa@mof.tt.org FU National Institutes of Health, USA [CA90522, CA108950] FX We thank C French, A Wilson and M Crowe for technical assistance, and Drs Z Andrysik and S Schwemberger for FACS analysis. This research is supported by the grants from National Institutes of Health, USA (CA90522 to KF and CA108950 to PS). NR 29 TC 25 Z9 25 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 11 PY 2008 VL 27 IS 40 BP 5288 EP 5302 DI 10.1038/onc.2008.161 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 346UW UT WOS:000259096100002 PM 18490919 ER PT J AU Taube, R Zhu, Q Xu, C Diaz-Griffero, F Sui, J Kamau, E Dwyer, M Aird, D Marasco, WA AF Taube, Ran Zhu, Quan Xu, Chen Diaz-Griffero, Felipe Sui, Jianhua Kamau, Erick Dwyer, Markryan Aird, Daniel Marasco, Wayne A. TI Lentivirus Display: Stable Expression of Human Antibodies on the Surface of Human Cells and Virus Particles SO PLOS ONE LA English DT Article AB Background: Isolation of human antibodies using current display technologies can be limited by constraints on protein expression, folding and post-translational modifications. Here we describe a discovery platform that utilizes self-inactivating (SIN) lentiviral vectors for the surface display of high-affinity single-chain variable region (scFv) antibody fragments on human cells and lentivirus particles. Methodology/Principal Findings: Bivalent scFvFc human antibodies were fused in frame with different transmembrane (TM) anchoring moieties to allow efficient high- level expression on human cells and the optimal TM was identified. The addition of an eight amino acid HIV-1 gp41 envelope incorporation motif further increased scFvFc expression on human cells and incorporation into lentiviral particles. Both antibody-displaying human cells and virus particles bound antigen specifically. Sulfation of CDR tyrosine residues, a property recently shown to broaden antibody binding affinity and antigen recognition was also demonstrated. High level scFvFc expression and stable integration was achieved in human cells following transduction with IRES containing bicistronic SIN lentivectors encoding ZsGreen when scFvFc fusion proteins were expressed from the first cassette. Up to 10(6)-fold enrichment of antibody expressing cells was achieved with one round of antigen coupled magnetic bead pre-selection followed by FACS sorting. Finally, the scFvFc displaying human cells could be used directly in functional biological screens with remarkable sensitivity. Conclusions/Significance: This antibody display platform will complement existing technologies by virtue of providing properties unique to lentiviruses and antibody expression in human cells, which, in turn, may aid the discovery of novel therapeutic human mAbs. C1 [Taube, Ran; Zhu, Quan; Xu, Chen; Diaz-Griffero, Felipe; Sui, Jianhua; Kamau, Erick; Dwyer, Markryan; Aird, Daniel; Marasco, Wayne A.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. [Taube, Ran; Zhu, Quan; Xu, Chen; Sui, Jianhua; Marasco, Wayne A.] Harvard Med Sch, Dept Med, Boston, MA USA. [Diaz-Griffero, Felipe] Harvard Med Sch, Dept Pathol, Boston, MA USA. RP Taube, R (reprint author), Ben Gurion Univ Negev, Dept Virol, IL-84105 Beer Sheva, Israel. EM Wayne_Marasco@dfci.harvard.edu OI SUI, JIANHUA/0000-0002-1272-9662 FU National Institutes of Health [AI061318, AI58804]; Israeli government [Bikura fellowship] FX This work has been supported by the National Institutes of Health grants, AI061318 (W. A. Marasco) and AI58804 (Q. Zhu). RT was supported by the Israeli government "Bikura" fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 16 Z9 16 U1 0 U2 5 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 SEP 11 PY 2008 VL 3 IS 9 AR e3181 DI 10.1371/journal.pone.0003181 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 422KF UT WOS:000264425900003 PM 18784843 ER PT J AU Taylor, BS Barretina, J Socci, ND DeCarolis, P Ladanyi, M Meyerson, M Singer, S Sander, C AF Taylor, Barry S. Barretina, Jordi Socci, Nicholas D. DeCarolis, Penelope Ladanyi, Marc Meyerson, Matthew Singer, Samuel Sander, Chris TI Functional Copy-Number Alterations in Cancer SO PLOS ONE LA English DT Article AB Understanding the molecular basis of cancer requires characterization of its genetic defects. DNA microarray technologies can provide detailed raw data about chromosomal aberrations in tumor samples. Computational analysis is needed (1) to deduce from raw array data actual amplification or deletion events for chromosomal fragments and (2) to distinguish causal chromosomal alterations from functionally neutral ones. We present a comprehensive computational approach, RAE, designed to robustly map chromosomal alterations in tumor samples and assess their functional importance in cancer. To demonstrate the methodology, we experimentally profile copy number changes in a clinically aggressive subtype of soft-tissue sarcoma, pleomorphic liposarcoma, and computationally derive a portrait of candidate oncogenic alterations and their target genes. Many affected genes are known to be involved in sarcomagenesis; others are novel, including mediators of adipocyte differentiation, and may include valuable therapeutic targets. Taken together, we present a statistically robust methodology applicable to high-resolution genomic data to assess the extent and function of copy-number alterations in cancer. C1 [Taylor, Barry S.; Socci, Nicholas D.; Sander, Chris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10021 USA. [Taylor, Barry S.] Weill Cornell Grad Sch Med Sci, Dept Physiol & Biophys, New York, NY USA. [Barretina, Jordi; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Barretina, Jordi; Meyerson, Matthew] Massachusetts Inst Technol MIT, Broad Inst Harvard, Cambridge, MA USA. [DeCarolis, Penelope; Singer, Samuel] Memorial Sloan Kettering Canc Ctr, Sarcoma Biol Lab, Sarcoma Dis Management Program, New York, NY USA. [Ladanyi, Marc] Memorial Sloan Kettering Canc Ctr, Dept Pathol & Human Oncol, Pathogenesis Program, New York, NY USA. [Singer, Samuel] Memorial Sloan Kettering Canc Ctr, Dept Surg, New York, NY USA. RP Taylor, BS (reprint author), Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, 1275 York Ave, New York, NY 10021 USA. EM copy-number@cbio.mskcc.org RI sander, chris/H-1452-2011; Meyerson, Matthew/E-7123-2012 FU The Soft Tissue Sarcoma Program Project [P01 CA047179]; The Sarcoma Genome Project; The Kristen Ann Carr Fund FX This work was supported in part by: The Soft Tissue Sarcoma Program Project (P01 CA047179, S.S., N.D.S and C.S.), The Sarcoma Genome Project, and by The Kristen Ann Carr Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 79 Z9 81 U1 0 U2 7 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 SEP 11 PY 2008 VL 3 IS 9 AR e3179 DI 10.1371/journal.pone.0003179 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 422KF UT WOS:000264425900001 PM 18784837 ER PT J AU Saha, S Guiton, G Wimmers, PF Wilkerson, L AF Saha, Somnath Guiton, Gretchen Wimmers, Paul F. Wilkerson, LuAnn TI Student body racial and ethnic composition and diversity-related outcomes in US medical schools SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CULTURAL COMPETENCE; HIGHER-EDUCATION; CARE; PERSPECTIVES; PHYSICIANS; WORKFORCE; IMPACT; POLICY AB Context Many medical schools assert that a racially and ethnically diverse student body is an important element in educating physicians to meet the needs of a diverse society. However, there is limited evidence addressing the educational effects of student body racial diversity. Objective To determine whether student body racial and ethnic diversity is associated with diversity- related outcomes among US medical students. Design, Setting, and Participants A Web- based survey ( Graduation Questionnaire) administered by the Association of American Medical Colleges of 20 112 graduating medical students ( 64% of all graduating students in 2003 and 2004) from 118 allopathic medical schools in the United States. Historically black and Puerto Rican medical schools were excluded. Main Outcome Measures Students' self- rated preparedness to care for patients from other racial and ethnic backgrounds, attitudes about equity and access to care, and intent to practice in an underserved area. Results White students within the highest quintile for student body racial and ethnic diversity, measured by the proportion of underrepresented minority ( URM) students, were more likely to rate themselves as highly prepared to care for minority populations than those in the lowest diversity quintile ( 61.1% vs 53.9%, respectively; P <. 001; adjusted odds ratio [ OR], 1.33; 95% confidence interval [ CI], 1.13- 1.57). This association was strongest in schools in which students perceived a positive climate for interracial interaction. White students in the highest URM quintile were also more likely to have strong attitudes endorsing equitable access to care ( 54.8% vs 44.2%, respectively; P <. 001; adjusted OR, 1.42; 95% CI, 1.15- 1.74). For nonwhite students, after adjustment there were no significant associations between student body URM proportions and diversity- related outcomes. Student body URM proportions were not associated with white or nonwhite students' plans to practice in underserved communities, although URM students were substantially more likely than white or nonwhite/ non- URM students to plan to serve the underserved ( 48.7% vs 18.8% vs 16.2%, respectively; P <. 001). Conclusion Student body racial and ethnic diversity within US medical schools is associated with outcomes consistent with the goal of preparing students to meet the needs of a diverse population. C1 [Saha, Somnath] Oregon Hlth & Sci Univ, Gen Internal Med Sect, Portland VA Med Ctr, Dept Med, Portland, OR 97239 USA. [Guiton, Gretchen] Univ Colorado, Sch Med, Educ Dev & Res Off, Denver, CO USA. [Wimmers, Paul F.; Wilkerson, LuAnn] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Saha, S (reprint author), Oregon Hlth & Sci Univ, Gen Internal Med Sect, Portland VA Med Ctr, Dept Med, P3HSRD,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sahas@ohsu.edu FU Advanced Research Career Development award; US Department of Veterans Affairs Health Services Research and Development Service FX Dr Saha was supported by an Advanced Research Career Development award from the US Department of Veterans Affairs Health Services Research and Development Service when this study was conducted. The Association of American Medical Colleges (AAMC) collected and manages the Graduation Questionnaire data analyzed for this study. Dr Saha has served on Advisory Committees for AAMC initiatives related to medical school diversity. NR 31 TC 82 Z9 82 U1 3 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 10 PY 2008 VL 300 IS 10 BP 1135 EP 1145 DI 10.1001/jama.300.10.1135 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 345ZR UT WOS:000259038700006 PM 18780842 ER PT J AU Volpp, KG Landrigan, CP AF Volpp, Kevin G. Landrigan, Christopher P. TI Building physician work hour regulations from first principles and best evidence SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MEDICAL ERRORS; INTERNS; MORTALITY; PERFORMANCE; DURATION; SHIFTS; REFORM; RISK; CARE C1 [Volpp, Kevin G.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Vet Adm Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Landrigan, Christopher P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Landrigan, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. RP Volpp, KG (reprint author), Univ Penn, Sch Med, Dept Med, 1232 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu FU AHRQ HHS [U18 HS15906]; NHLBI NIH HHS [R01 HL082637] NR 15 TC 19 Z9 19 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 10 PY 2008 VL 300 IS 10 BP 1197 EP 1199 DI 10.1001/jama.300.10.1197 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 345ZR UT WOS:000259038700012 PM 18780848 ER PT J AU Dahlberg, SE Gray, RJ Johnson, BE AF Dahlberg, Suzanne E. Gray, Robert J. Johnson, Bruce E. TI Gefitinib for recurrent non-small-cell lung cancer: All things are not created equal SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID EQUIVALENCE RANDOMIZED-TRIALS; PLATINUM-BASED CHEMOTHERAPY; SUPPORTIVE CARE; NONINFERIORITY; DOCETAXEL; SURVIVAL; QUALITY; IRESSA; DESIGN C1 [Dahlberg, Suzanne E.; Gray, Robert J.; Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dahlberg, SE (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 12 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2008 VL 26 IS 26 BP 4233 EP 4235 DI 10.1200/JCO.2008.17.0837 PG 3 WC Oncology SC Oncology GA 350KD UT WOS:000259350400002 PM 18779608 ER PT J AU Smith, MR Bae, K Efstathiou, JA Hanks, GE Pilepich, MV Sandler, HM Shipley, WU AF Smith, Matthew R. Bae, Kyounghwa Efstathiou, Jason A. Hanks, Gerald E. Pilepich, Miljenko V. Sandler, Howard M. Shipley, William U. TI Diabetes and mortality in men with locally advanced prostate cancer: RTOG 92-02 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; ANDROGEN DEPRIVATION; COMPETING RISK; US POPULATION; UNITED-STATES; OBESITY; FAILURE; HYPERINSULINEMIA; RADIOTHERAPY; THERAPY AB Purpose Diabetes is associated with lower risk of prostate cancer. Most men with diabetes are obese, and obesity is associated with greater prostate cancer mortality. Whether diabetes influences outcomes after prostate cancer diagnosis is unknown. Patients and Methods We assessed the relationship between prevalent diabetes and mortality using data from Radiation Therapy Oncology Group Protocol 92-02, a large randomized trial of men (N = 1,554) treated with radiation therapy and short-term versus long-term adjuvant goserelin for locally advanced prostate cancer. Regression and proportional hazard models were performed to evaluate relationships between prevalent diabetes and all-cause mortality, prostate cancer mortality, and non-prostate cancer mortality. Covariates included age, race, tumor stage, Gleason score, prostate-specific antigen, weight, and treatment arm. Results There were a total of 765 deaths; 210 (27%) were attributed to prostate cancer. In univariate analyses, prevalent diabetes was associated with greater all-cause mortality and non-prostate cancer mortality but not prostate cancer mortality. After controlling for other covariates, prevalent diabetes remained significantly associated with greater all-cause mortality and non-prostate cancer mortality (hazard ratio [HR] = 2.12; 95% CI, 1.69 to 2.66; P < .0001) but not prostate cancer mortality (HR = 0.80; 95% CI, 0.51 to 1.25; P = .34). In contrast, weight was associated with greater prostate cancer mortality (HR = 1.77; 95% CI, 1.22 to 2.55; P = .002) but not all-cause or non-prostate cancer mortality. Conclusion Weight but not prevalent diabetes is associated with greater prostate cancer mortality in men receiving combined modality treatment for locally advanced disease. These observations suggest that the association between obesity and greater prostate cancer mortality is mediated by mechanism(s) other than the characteristic metabolic alterations of diabetes. C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Fox Chase Canc Ctr, Dept Stat, Radiat Therapy Oncol Grp, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Univ Calif Los Angeles, Sch Med, Dept Radiat Oncol, Los Angeles, CA USA. Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU National Cancer Institute [RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115]; NIH [K24 CA121990]; Prostate Cancer Foundation FX Supported by Grants No. RTOG U10 CA21661, CCOP U10 CA37422, and Stat U10 CA32115 from the National Cancer Institute. M. R. S. is supported by an NIH K24 Midcareer Investigator Award (K24 CA121990) and competitive research awards from the Prostate Cancer Foundation. NR 26 TC 35 Z9 35 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 SEP 10 PY 2008 VL 26 IS 26 BP 4333 EP 4339 DI 10.1200/JCO.2008.16.5845 PG 7 WC Oncology SC Oncology GA 350KD UT WOS:000259350400017 PM 18779620 ER PT J AU Lathan, CS Neville, BA Earle, CC AF Lathan, Christopher S. Neville, Bridget A. Earle, Craig C. TI Racial composition of hospitals: Effects on surgery for early-stage non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID ACUTE MYOCARDIAL-INFARCTION; COMORBIDITY INDEX; DISPARITIES; CARE; MORTALITY; RESECTION; VOLUME; CHEMOTHERAPY; VALIDATION; SURVIVAL AB Purpose Black patients undergo potentially curative surgery for early-stage lung cancer at a lower rate when compared with white patients. Our study examines the relationship between the percentage of black patients treated at a hospital to determine whether it affects the likelihood of obtaining cancer-directed surgery for patients with non-small-cell lung cancer (NSCLC). Patients and Methods We examined claims data of Medicare-eligible patients with nonmetastatic NSCLC living in areas monitored by the Surveillance, Epidemiology, and End Results program between 1991 and 2001. Hospitals were categorized by the percentage of black patients seen: <= 8%, more than 8% to 29%, and >= 30%. Logistic regression with clustering analysis was used to calculate the odds of undergoing surgical resection. Results Among 9,688 patients with NSCLC, 59% of white patients were seen at a hospital that had <= 8% black patients, whereas 60% of black patients were seen in hospitals that had >= 30% black patients. Regression analysis revealed that hospital racial composition of 30% or greater black patients had a significant negative effect on the likelihood of undergoing surgery for all patients (odds ratio [OR] = 0.71; 95% CI, 0.57 to 0.87), with black race (OR = 0.69; 95% CI, 0.56 to 0.85) and being seen at a low-volume hospital (OR = 0.64; 95% CI, 0.0.49 to 0.83) having a significant negative impact on likelihood of undergoing surgery. Conclusion Our study results indicate that patient and hospital characteristics are significant predictors of undergoing surgery for Medicare beneficiaries with localized lung cancer. Further examination of the role of the patient-, provider-, and hospital-level factors, in association with the decision to pursue surgical treatment of localized lung cancers, is needed. C1 [Lathan, Christopher S.; Neville, Bridget A.; Earle, Craig C.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Div Populat Sci, Dept Med Oncol, Boston, MA 02115 USA. RP Lathan, CS (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Div Populat Sci, Dept Med Oncol, 44 Binney St,454-STE 21-24, Boston, MA 02115 USA. EM christopher_lathan@dfci.harvard.edu FU NCI NIH HHS [R25 CA092203, KO1 CA124581-01A, 5R25 CA092203-04] NR 31 TC 31 Z9 31 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2008 VL 26 IS 26 BP 4347 EP 4352 DI 10.1200/JCO.2007.15.5291 PG 6 WC Oncology SC Oncology GA 350KD UT WOS:000259350400019 PM 18779622 ER PT J AU Jakobs, TC Koizumi, A Masland, RH AF Jakobs, Tatjana C. Koizumi, Amane Masland, Richard H. TI The spatial distribution of glutamatergic inputs to dendrites of retinal ganglion cells SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE retinal ganglion cells; PSD95; excitatory synaptic input; synapse distribution; organotypic retina culture ID UNDERLYING DIRECTIONAL SELECTIVITY; MARMOSET CALLITHRIX-JACCHUS; LOCAL EDGE DETECTORS; RABBIT RETINA; PRIMATE RETINA; CAT RETINA; RECEPTOR SUBUNITS; MAMMALIAN RETINA; SYNAPTIC INPUTS; MACAQUE RETINA AB The spatial pattern of excitatory glutamatergic input was visualized in a large series of ganglion cells of the rabbit retina, by using particle-mediated gene transfer of an expression plasmid for postsynaptic density 95-green fluorescent protein (PSD95-GFP). PSD95-GFP was confirmed as a marker of excitatory input by co-localization with synaptic ribbons (RIBEYE and kinesin 11) and glutamate receptor subunits. Despite wide variation in the size, morphology, and functional complexity of the cells, the distribution of excitatory synaptic inputs followed a single set of rules: 1) the linear density of synaptic inputs (PSD95 sites/linear mu m) varied surprisingly little and showed little specialization within the arbor; 2) the total density of excitatory inputs across individual arbors peaked in a ring-shaped region surrounding the soma, which is in accord with high-resolution maps of receptive field sensitivity in the rabbit; and 3) the areal density scaled inversely with the total area of the dendritic arbor, so that narrow dendritic arbors receive more synapses per unit area than large ones. To achieve sensitivity comparable to that of large cells, those that report upon a small region of visual space may need to receive a denser synaptic input from within that space. J. Comp. Neurol. 510:221-236, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Jakobs, Tatjana C.; Koizumi, Amane; Masland, Richard H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Masland, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thier 429,50 Blossom St, Boston, MA 02114 USA. EM richard_masland@hms.harvard.edu RI Koizumi, Amane/E-7771-2011; OI Jakobs, Tatjana/0000-0002-8104-9206 FU NEI NIH HHS [R01 EY017169, R01 EY017169-02, R01-EY017169] NR 78 TC 37 Z9 37 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 10 PY 2008 VL 510 IS 2 BP 221 EP 236 DI 10.1002/cne.21795 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 336IL UT WOS:000258357400007 PM 18623177 ER PT J AU Ho, C Shanmugasundararaj, S Miller, KW Malinowski, SA Cook, AC Slater, SJ AF Ho, Cojen Shanmugasundararaj, Sivananthaperumal Miller, Keith W. Malinowski, Steve A. Cook, Anthony C. Slater, Simon J. TI Interaction of anesthetics with the Rho GTPase regulator Rho GDP dissociation inhibitor SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; NICOTINIC ACETYLCHOLINE-RECEPTOR; BINDING-SITE; TRYPTOPHAN FLUORESCENCE; COMPETITIVE-BINDING; ALCOHOLS; DOMAIN; ALPHA; ACTIVATION; HALOTHANE AB The physiological effects of anesthetics have been ascribed to their interaction with hydrophobic sites within functionally relevant CNS proteins. Studies have shown that volatile anesthetics compete for luciferin binding to the hydrophobic substrate binding site within firefly luciferase and inhibit its activity (Franks, N. P., and Lieb, W. R. (1984) Nature 310, 599-601). To assess whether anesthetics also compete for ligand binding to a mammalian signal transduction protein, we investigated the interaction of the volatile anesthetic, halothane, with the Rho GDP dissociation inhibitor (RhoGDI alpha), which binds the geranylgeranyl moiety of GDP-bound Rho GTPases. Consistent with the existence of a discrete halothane binding site, the intrinsic tryptophan fluorescence of RhoGDI alpha was quenched by halothane (2-bromo2-chloro-1,1,1-trifluoroethane) in a saturable, concentration-dependent manner. Bromine quenching of tryptophan fluorescence is short-range and W192 and W194 of the RhoGDI alpha. are located within the geranylgeranyl binding pocket, suggesting that halothane binds within this region. Supporting this, N-acetyl-geranylgeranyl cysteine reversed tryptophan quenching by halothane. Short chain n-alcohols (n < 6) also reversed tryptophan quenching, suggesting that RhoGDI alpha may also bind n-alkanols. Consistent with this, E193 was photolabeled by 3-azibutanol. This residue is located in the vicinity of, but outside, the geranylgeranyl chain binding pocket, suggesting that the alcohol binding site is distinct from that occupied by halothane. Supporting this, N-acetyl-geranylgeranyl cysteine enhanced E193 photolabeling by 3-azibutanol. Overall, the results suggest that halothane binds to a site within the geranylgeranyl chain binding pocket of RhoGDI alpha, whereas alcohols bind to a distal site that interacts allosterically with this pocket. C1 [Ho, Cojen; Malinowski, Steve A.; Cook, Anthony C.; Slater, Simon J.] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. [Shanmugasundararaj, Sivananthaperumal; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Shanmugasundararaj, Sivananthaperumal; Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Slater, SJ (reprint author), Complete Healthcare Commun Inc, Chadds Ford, PA 19317 USA. EM Simon.Slater@CHCinc.com FU NIAAA NIH HHS [R01 AA010990, AA010990]; NIGMS NIH HHS [R01 GM069726, GM069726] NR 59 TC 4 Z9 4 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 9 PY 2008 VL 47 IS 36 BP 9540 EP 9552 DI 10.1021/bi800544d PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 343PT UT WOS:000258866700020 PM 18702520 ER PT J AU Nakazawa, G Finn, AV Joner, M Ladich, E Kutys, R Mont, EK Gold, HK Burke, AP Kolodgie, FD Virmani, R AF Nakazawa, Gaku Finn, Aloke V. Joner, Michael Ladich, Elena Kutys, Robert Mont, Erik K. Gold, Herman K. Burke, Allen P. Kolodgie, Frank D. Virmani, Renu TI Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients - An autopsy study SO CIRCULATION LA English DT Article DE myocardial infarction; stents; thrombosis ID BARE-METAL STENTS; CORONARY-ARTERY; UNCOATED STENTS; PACLITAXEL; HUMANS; IMPLANTATION; RESTENOSIS; PREDICTORS; OUTCOMES; DISEASE AB Background-The long-term safety of drug-eluting stents (DES) for acute myocardial infarction (AMI) remains uncertain. Using autopsy data, we evaluated the pathological responses of the stented segment in patients treated with DES for AMI and compared with patients with stable angina. Methods and Results-From the CVPath Registry of 138 DES autopsies, we identified 25 patients who presented with AMI and had an underlying necrotic core with a ruptured fibrous cap. Twenty-six patients who had stable angina with thick-cap fibroatheroma treated by DES were selected as controls. Histomorphometric analysis was performed in patients with >30-day stent duration. We compared the response to stenting at the culprit site in these 2 groups and to nonculprit sites within each stent. Late stent thrombosis was significantly less frequent in stable (11%) than in AMI (41%; P = 0.04) patients. Although neointimal thickness in the AMI culprit site was significantly less (median, 0.04 mm; interquartile range [IQR], 0.02 to 0.09 mm), the prevalence of uncovered struts (49%; IQR, 16% to 96%), fibrin deposition (63 +/- 28%), and inflammation (35%; IQR, 27% to 49%) were significantly greater compared with the culprit site in stable patients (neointimal thickness: 0.11 mm [IQR, 0.07 to 0.21 mm], P = 0.008; uncovered struts: 9% [IQR, 0% to 39%], P = 0.01; fibrin: 36 +/- 27%, P = 0.008; inflammation, 17% [IQR, 7% to 25%], P = 0.003) and the nonculprit site within each stent. Conclusions-Vessel healing at the culprit site in AMI patients treated with DES is substantially delayed compared with the culprit site in patients receiving DES for stable angina, emphasizing the importance of underlying plaque morphology in the arterial response to DES. Our data suggest an increased risk of thrombotic complications in patients treated with DES for AMI. C1 [Nakazawa, Gaku; Joner, Michael; Ladich, Elena; Kutys, Robert; Burke, Allen P.; Kolodgie, Frank D.; Virmani, Renu] CVPath Inst Inc, Gaithersburg, MD 20878 USA. [Finn, Aloke V.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Mont, Erik K.] Miami Dade Cty Med Examiner Dept, Miami, FL USA. [Gold, Herman K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Virmani, R (reprint author), CVPath Inst Inc, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 26 TC 308 Z9 323 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 9 PY 2008 VL 118 IS 11 BP 1138 EP 1145 DI 10.1161/CIRCULATIONAHA.107.762047 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 345ZX UT WOS:000259039300006 PM 18725485 ER PT J AU Finn, AV Leinbach, RC AF Finn, Aloke V. Leinbach, Robert C. TI Herman Kalman Gold, MD - 1940-2008 - In memoriam SO CIRCULATION LA English DT Biographical-Item C1 [Finn, Aloke V.] Emory Univ, Sch Med, Dept Internal Med, Atlanta, GA 30308 USA. [Leinbach, Robert C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Finn, AV (reprint author), Emory Univ, Sch Med, Dept Internal Med, Emory Crawford Long Hosp, 550 Peachtree St NE, Atlanta, GA 30308 USA. EM avfinn@emory.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 9 PY 2008 VL 118 IS 11 BP 1212 EP 1213 DI 10.1161/CIRCULATIONAHA.108.808584 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 345ZX UT WOS:000259039300014 ER PT J AU Giraldez, RR Giugliano, RP Mohanavelu, S Murphy, SA McCabe, CH Cannon, CP Braunwald, E AF Giraldez, Roberto R. Giugliano, Robert P. Mohanavelu, Satishkumar Murphy, Sabina A. McCabe, Carolyn H. Cannon, Christopher P. Braunwald, Eugene TI Baseline low-density lipoprotein cholesterol is an important predictor of the benefit of intensive lipid-lowering therapy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE LDL-C; lipid-lowering therapy; atorvastatin; pravastatin; outcomes ID CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; CONTROLLED-TRIAL; STATIN THERAPY; ATORVASTATIN; SIMVASTATIN; PRAVASTATIN; SAFETY; EFFICACY AB Objectives This study sought to determine whether the benefit of intensive lipid-lowering therapy (LLT) is dependent on baseline low-density lipoprotein cholesterol (LDL-C). Background Aggressive LDL-C reduction with statins improves cardiovascular outcomes in acute and chronic coronary heart disease (CHD). The importance of baseline LDL-C is unclear. Methods We compared 2-year composites of death, myocardial infarction (MI), unstable angina, revascularization > 30 days, and stroke (primary end point), and CHD death, MI, and revascularization > 30 days (secondary end point) in 2,986 statin-naive patients with recent acute coronary syndrome (ACS) randomized to atorvastatin 80 mg versus pravastatin 40 mg in the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy Thrombolysis In Myocardial Infarction 22) study stratified by quartiles of baseline LDL-C. Multivariable models assessed whether the treatment benefit was dependent on baseline LDL-C. Results A significant reduction in the hazards of the primary (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.47 to 0.85, p = 0.002) and secondary (HR: 0.57, 95% CI: 0.42 to 0.79, p = 0.001) end points occurred in patients within the highest quartile (> 132 mg/dl) of baseline LDL-C treated with atorvastatin 80 mg. The benefit of intensive therapy progressively declined as baseline LDL-C decreased. The lowest quartile (LDL-C <= 92 mg/dl) experienced similar rates of the primary (HR: 0.93, 95% CI: 0.69 to 1.25, p = 0.63) and secondary (HR: 0.98, 95% CI: 0.71 to 1.35, p = 0.89) end points. Adjusted interaction tests between treatment and highest versus lowest baseline LDL-C quartile were significant for the primary and secondary end points (p = 0.03 and p = 0.007, respectively). Analyzing baseline LDL-C as a continuous variable, atorvastatin 80 mg was associated with improved outcomes provided the baseline LDL-C was > 66 mg/dl. Conclusions A progressive reduction in the benefit of intensive LLT with atorvastatin 80 mg over pravastatin 40 mg occurred in statin-naive ACS patients as baseline LDL-C declined. (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 [PROVE IT-TIMI 22]; NCT00382460). C1 [Giraldez, Roberto R.; Giugliano, Robert P.; Mohanavelu, Satishkumar; Murphy, Sabina A.; McCabe, Carolyn H.; Cannon, Christopher P.; Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Div Cardiovasc,TIMI Study Grp, Boston, MA USA. RP Giugliano, RP (reprint author), TIMI Study Off, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org NR 22 TC 36 Z9 43 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 SEP 9 PY 2008 VL 52 IS 11 BP 914 EP 920 DI 10.1016/j.jacc.2008.05.046 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 344FH UT WOS:000258911700005 PM 18772061 ER PT J AU Desikan, RS Fischl, B Cabral, HJ Kemper, TL Guttmann, CRG Blacker, D Hyman, BT Albert, MS Killiany, RJ AF Desikan, R. S. Fischl, B. Cabral, H. J. Kemper, T. L. Guttmann, C. R. G. Blacker, D. Hyman, B. T. Albert, M. S. Killiany, R. J. TI MRI measures of temporoparietal regions show differential rates of atrophy during prodromal AD SO NEUROLOGY LA English DT Article ID SURFACE-BASED ANALYSIS; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; ENTORHINAL CORTEX; BRAIN ATROPHY; WORK GROUP; DEMENTIA; PROGRESSION; EVOLUTION; ASSOCIATION AB Background: MRI studies have demonstrated differential rates of atrophy in the entorhinal cortex and hippocampus during the prodromal phase of Alzheimer disease (AD). The current study was designed to determine whether a broader set of temporoparietal regions show differential rates of atrophy during the evolution of AD. Methods: Sixteen regions of interest ( ROIs) were analyzed on MRI scans obtained at baseline and follow-up in 66 subjects comprising three groups: controls = individuals who were cognitively normal at both baseline and follow-up; nonconverters = subjects with mild cognitive impairment (MCI) at both baseline and follow-up; converters had MCI at baseline but had progressed to AD at follow-up. Results: Annualized percent change was analyzed with multivariate analysis of variance (MANOVA), covaried for age. The MANOVA demonstrated an effect of group (p = 0.004). Post hoc comparisons demonstrated greater rates of atrophy for converters vs nonconverters for six ROIs: hippocampus, entorhinal cortex, temporal pole, middle temporal gyrus, fusiform gyrus, and inferior temporal gyrus. Converters showed differentially greater rates of atrophy than controls in five of the same ROIs (and inferior parietal lobule). Rates of change in clinical status were correlated with the atrophy rates in these regions. Comparisons between controls and nonconverters demonstrated no differences. Conclusion: These results demonstrate that temporoparietal regions show differential rates of atrophy on MRI during prodromal Alzheimer disease (AD). MRI data correlate with measures of clinical severity and cognitive decline, suggesting the potential of these regions of interest as antemortem markers of prodromal AD. C1 [Killiany, R. J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Ctr Biomed Imaging, Boston, MA 02118 USA. [Fischl, B.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Blacker, D.; Killiany, R. J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hyman, B. T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fischl, B.] MIT, Comp Sci & Artificial Intelligence Lab, Boston, MA USA. [Cabral, H. J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Killiany, R. J.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02118 USA. [Guttmann, C. R. G.; Killiany, R. J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Albert, M. S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Killiany, RJ (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, Ctr Biomed Imaging, Boston, MA 02118 USA. EM killiany@bu.edu FU NCRR NIH HHS [P41-RR14075, R01-RR16594, U24-RR021382]; NIA NIH HHS [P01 AG004953-230006, P01 AG004953, P01 AG004953-230001, P01-AG04953]; NIBIB NIH HHS [R01-EB001550]; NINDS NIH HHS [R01 NS052585] NR 37 TC 54 Z9 54 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 9 PY 2008 VL 71 IS 11 BP 819 EP 825 DI 10.1212/01.wnl.0000320055.57329.34 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 345ZU UT WOS:000259039000008 PM 18672473 ER PT J AU Mansy, SS Szostak, JW AF Mansy, Sheref S. Szostak, Jack W. TI Thermostability of model protocell membranes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE origin of life; RNA world; synthetic biology; vesicle; prebiotic ID FATTY-ACID VESICLES; POLYMERASE; LIFE; ENCAPSULATION; AMPHIPHILES; STABILITY; LIPOSOMES; GROWTH; RNA AB The earliest cells may have consisted of a self-replicating genetic polymer encapsulated within a self-replicating membrane vesicle. Here, we show that vesicles composed of simple single-chain amphiphiles such as fatty acids, fatty alcohols, and fatty-acid glycerol esters are extremely thermostable and retain internal RNA and DNA oligonucleotides at temperatures ranging from 0 degrees C to 100 degrees C. The strands of encapsulated double-stranded DNA can be separated by denaturation at high temperature while being retained within vesicles, implying that strand separation in primitive protocells could have been mediated by thermal fluctuations without the loss of genetic material from the protocell. At elevated temperatures, complex charged molecules such as nucleotides cross fatty-acid-based membranes very rapidly, suggesting that high temperature excursions may have facilitated nutrient uptake before the evolution of advanced membrane transporters. The thermostability of these membranes is consistent with the spontaneous replication of encapsulated nucleic acids by the alternation of template-copying chemistry at low temperature with strand-separation and nutrient uptake at high temperature. C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu RI Mansy, Sheref/E-6266-2010; OI Mansy, Sheref/0000-0003-2382-198X FU National Institutes of Health [F32 GM07450601]; NASA Exobiology Program [EXB02-0031-0018] FX We thank J. P. Schrum, R. J. Bruckner, M. M. Hanczyc, B. Seelig, 1. A. Chen, S. Tobe, T. F. Zhu, Q. Dufton, J. Iwasa, F. P. Seebeck, A. Ricardo, A. J. Bell, and M. Sam for helpful discussions. This work was supported by NASA Exobiology Program Grant EXB02-0031-0018. J.W.S. is an Investigator of the Howard Hughes Medical Institute. S.S.M. was supported in part by the National Institutes of Health Award F32 GM07450601. NR 23 TC 61 Z9 64 U1 4 U2 30 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 SEP 9 PY 2008 VL 105 IS 36 BP 13351 EP 13355 DI 10.1073/pnas.0805086105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 349AR UT WOS:000259251700033 PM 18768808 ER PT J AU Ban, LQ Zhang, J Wang, LM Kuhtreiber, W Burger, D Faustman, DL AF Ban, Liqin Zhang, Jack Wang, Limei Kuhtreiber, Willem Burger, Douglas Faustman, Denise L. TI Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE agonist antibodies; autoimmunity; apoptosis; TNFR2; Crohn's ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; MAJOR HISTOCOMPATIBILITY COMPLEX; MULTIPLE-SCLEROSIS; CROHNS-DISEASE; P75 RECEPTOR; IN-VITRO; NOD MICE; ALPHA; APOPTOSIS AB Human autoimmune (AI) diseases are difficult to treat, because immunosuppressive drugs are nonspecific, produce high levels of adverse effects, and are not based on mechanistic understanding of disease. Destroying the rare autoreactive T lymphocytes causing Al diseases would improve treatment. In animal models, TNF selectively kills autoreactive T cells, thereby hampering disease onset or progression. Here, we seek to determine, in fresh human blood, whether TNF or agonists of TNF selectively kill autoreactive T cells, while sparing normal T cells. We isolated highly pure CD4 or CD8 T cells from patients with type 1 diabetes (n = 675), other AI diseases, and healthy controls (n = 512). Using two cell death assays, we found that a subpopulation of CD8, but not CD4, T cells in patients' blood was vulnerable to TNF or TNF agonist-induced death. One agonist for the TNFR2 receptor exhibited a dose-response pattern of killing. in type 1 diabetes, the subpopulation of T cells susceptible to TNF or TNFR2 agonist-induced death was traced specifically to autoreactive T cells to insulin, a known autoantigen. Other activated and memory T cell populations were resistant to TNF-triggered death. This study shows that autoreactive T cells, although rare, can be selectively destroyed in isolated human blood. TNF and a TNFR2 agonist may offer highly targeted therapies, with the latter likely to be less systemically toxic. C1 [Faustman, Denise L.] Massachusetts Gen Hosp, Dept Immunobiol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Dept Immunobiol, Bldg 149,13th St, Boston, MA 02129 USA. EM faustman@helix.mgh.harvard.edu FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-13] NR 36 TC 43 Z9 44 U1 2 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 9 PY 2008 VL 105 IS 36 BP 13644 EP 13649 DI 10.1073/pnas.0803429105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 349AR UT WOS:000259251700083 PM 18755894 ER PT J AU Cannon, CP Greenberg, BH AF Cannon, Christopher P. Greenberg, Barry H. TI Risk stratification and prognostic factors in the post-myocardial infarction patient SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; LEFT-VENTRICULAR DYSFUNCTION; BRAIN NATRIURETIC PEPTIDE; DENSITY-LIPOPROTEIN CHOLESTEROL; CONGESTIVE-HEART-FAILURE; UNSTABLE ANGINA; STATIN THERAPY; TROPONIN-I AB Among the 5 million patients presenting to emergency departments with chest pain each year in the United States, approximately 1 million are diagnosed with myocardial infarction (MI). Physicians have the difficult task of making decisions regarding admission and treatment and identifying patients at high risk for adverse outcomes, such as early mortality, left ventricular dysfunction (LVD), and heart failure. Several measures can be implemented in the process of risk assessment, including clinical judgment, electrocardiographic and echocardiographic findings, and the presence of biomarkers. Biomarkers-which can be classified as antecedent, screening, diagnostic, staging, or prognostic-may help identify the subset of patients who need early intervention and/or intensive therapy. Using a multimarker strategy that combines a marker of hemodynamic stress (brain natriuretic peptide) or of inflammation (Creactive protein) with a marker of necrosis (cardiac troponin) may help to risk-stratify patients, guide treatment, and optimize admission and discharge decisions. This article discusses the potential benefits of risk assessment tools in the management of post-MI patients with LVD. (C) 2008 Elsevier Inc. All rights reserved. C1 [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Greenberg, Barry H.] Univ Calif San Diego, Div Cardiol, San Diego, CA 92103 USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM cpcannon@partners.org NR 53 TC 7 Z9 9 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 SEP 8 PY 2008 VL 102 IS 5A SU S BP 13G EP 20G DI 10.1016/j.amjcard.2008.06.006 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 342NI UT WOS:000258790400003 PM 18722187 ER PT J AU Goldstein, NE Back, AL Morrison, S AF Goldstein, Nathan E. Back, Anthony L. Morrison, Sean TI Titrating guidance - A model to guide physicians in assisting patients and family members who are facing complex decisions SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BREAST-CANCER; OF-LIFE; CARE; PREFERENCES; INFORMATION; DEPRESSION; HEALTH; END AB Over the last century, developments in new medical treatments have led to an exponential increase in longevity, but, as a consequence, patients may be left with chronic illness associated with long-term severe functional and cognitive disability. Patients and their families are often forced to make a difficult and complex choice between death and long-term debility, neither of which is an acceptable outcome. Traditional models of medical decision making, however, do not fully address how clinicians should best assist with these decisions. Herein, we present a new paradigm that demonstrates how the role of the physician changes over time in response to the curved relationship between the predictability of a patient's outcome and the chance of returning to an acceptable quality of life. To translate this model into clinical practice, we propose a 5-step model for physicians with which they can (1) determine at which point the patient is on our model; (2) identify the cognitive factors and preferences for outcomes that affect the decision-making process of the patient and his or her family; (3) reflect on their own reaction to the decision at hand; (4) acknowledge how these factors can be addressed in conversation; and (5) guide the patient and his or her family in creating a plan of care. This model can help improve patient-physician communication and decision making so that complex and difficult decisions can be turned into ones that yield to medical expertise, good communication, and personal caring. C1 [Goldstein, Nathan E.; Morrison, Sean] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, Hertzberg Palliat Care Inst Brookdale, New York, NY 10029 USA. [Goldstein, Nathan E.; Morrison, Sean] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Back, Anthony L.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. RP Goldstein, NE (reprint author), Mt Sinai Sch Med, Dept Geriatr, 1 Gustave Levy Pl,Box 1070, New York, NY 10029 USA. EM Nathan.Goldstein@mssm.edu FU National Institute of Aging [K23AG025933]; National Cancer Institute [R2592055]; National Palliative Care Research Center; National Institute on Aging [K24AG22345] FX Dr Goldstein is supported by a Mentored Patient-Oriented Research Career Development Award (K23AG025933) from the National Institute of Aging. Dr Back is supported by grant R2592055 from the National Cancer Institute. Dr Morrison is supported by the National Palliative Care Research Center and a Mid-Career Investigator Award in Patient-Oriented Research Award (K24AG22345) from the National Institute on Aging. NR 28 TC 26 Z9 26 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 SEP 8 PY 2008 VL 168 IS 16 BP 1733 EP 1739 DI 10.1001/archinte.168.16.1733 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 345XI UT WOS:000259030600002 PM 18779459 ER PT J AU Grant, RW Wald, JS Schnipper, JL Gandhi, TK Poon, EG Orav, EJ Williams, DH Volk, LA Middleton, B AF Grant, Richard W. Wald, Jonathan S. Schnipper, Jeffrey L. Gandhi, Tejal K. Poon, Eric G. Orav, E. John Williams, Deborah H. Volk, Lynn A. Middleton, Blackford TI Practice-linked online personal health records for type 2 diabetes mellitus - A randomized controlled trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CARDIOVASCULAR-DISEASE; SELF-MANAGEMENT; AMBULATORY-CARE; MEDICAL RECORDS; DIGITAL DIVIDE; UNITED-STATES; RISK-FACTORS; PATIENT; COMPLICATIONS; INTERNET AB Background: Web-based personal health records (PHRs) have been advocated as a means to improve type 2 diabetes mellitus (DM) care. However, few Web-based systems are linked directly to the electronic medical record (EMR) used by physicians. Methods: We randomized 11 primary care practices. Intervention practices received access to a DM-specific PHR that imported clinical and medications data, provided patient-tailored decision support, and enabled the patient to author a "Diabetes Care Plan" for electronic submission to their physician prior to upcoming appointments. Active control practices received a PHR to update and submit family history and health maintenance information. All patients attending these practices were encouraged to sign up for online access. Results: We enrolled 244 patients with DM(37% of the eligible population with registered online access, 4% of the overall population of patients with DM). Study participants < .001) and lived in higher-income neighborhoods (median income, $53 784 vs $49 713; P < .001) but had similar baseline glycemic control compared with nonparticipants. More patients in the intervention arm had their DM treatment regimens adjusted (53% vs 15%; P < .001) compared with active controls. However, there were no significant differences in risk factor control between study arms after 1 year (P = .53). Conclusions: Previsit use of online PHR linked to the EMR increased rates of DM-related medication adjustment. Low rates of online patient account registration and good baseline control among participants limited the intervention's impact on overall risk factor control. Trial Registration: clinicaltrials.gov Identifier: NCT00251875 C1 [Grant, Richard W.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Schnipper, Jeffrey L.; Gandhi, Tejal K.; Poon, Eric G.; Orav, E. John; Williams, Deborah H.; Middleton, Blackford] Brigham & Womens Hosp, Boston, MA 02115 USA. [Grant, Richard W.; Schnipper, Jeffrey L.; Gandhi, Tejal K.; Poon, Eric G.; Orav, E. John; Middleton, Blackford] Harvard Univ, Sch Med, Boston, MA USA. [Wald, Jonathan S.; Poon, Eric G.; Middleton, Blackford] Partners Informat Syst, Clin Informat Res & Dev, Wellesley, MA USA. [Williams, Deborah H.; Volk, Lynn A.] Partners Informat Syst, Clin & Qual Anal, Wellesley, MA USA. RP Grant, RW (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50-9 Staniford St, Boston, MA 02114 USA. EM Rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 FU Agency for Healthcare Research and Quality [AHRQ R01 HS013660-02]; National Institute of Diabetes and Digestive and Kidney Diseases Career Development [K23 DK067452] FX This study was supported in part by a grant from the Agency for Healthcare Research and Quality (AHRQ R01 HS013660-02: Shared Online Health Records for Patient Safety and Care). Dr Grant is also supported by a National Institute of Diabetes and Digestive and Kidney Diseases Career Development Award (K23 DK067452). NR 36 TC 87 Z9 87 U1 3 U2 12 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 SEP 8 PY 2008 VL 168 IS 16 BP 1776 EP 1782 DI 10.1001/archinte.168.16.1776 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 345XI UT WOS:000259030600008 PM 18779465 ER PT J AU Morrison, RS Penrod, JD Cassel, JB Caust-Ellenbogen, M Litke, A Spragens, L Meier, DE AF Morrison, R. Sean Penrod, Joan D. Cassel, J. Brian Caust-Ellenbogen, Melissa Litke, Ann Spragens, Lynn Meier, Diane E. CA Palliative Care Leadership Ctr Out TI Cost savings associated with US hospital palliative care consultation programs SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CLUSTER RANDOMIZED-TRIAL; OF-LIFE CARE; PROPENSITY SCORES; IMPROVE CARE; END; OUTCOMES; IMPACT; FAMILIES; SERVICE; MODELS AB Background: Hospital palliative care consultation teams have been shown to improve care for adults with serious illness. This study examined the effect of palliative care teams on hospital costs. Methods: We analyzed administrative data from 8 hospitals with established palliative care programs for the years 2002 through 2004. Patients receiving palliative care were matched by propensity score to patients receiving usual care. Generalized linear models were estimated for costs per admission and per hospital day. Results: Of the 2966 palliative care patients who were discharged alive, 2630 palliative care patients (89%) were matched to 18 427 usual care patients, and of the 2388 palliative care patients who died, 2278 (95%) were matched to 2124 usual care patients. The palliative care patients who were discharged alive had an adjusted net savings of $1696 in direct costs per admission (P = .004) and $279 in direct costs per day (P < .001) including significant reductions in laboratory and intensive care unit costs compared with usual care patients. The palliative care patients who died had an adjusted net savings of $4908 in direct costs per admission (P = .003) and $374 in direct costs per day (P < .001) including significant reductions in pharmacy, laboratory, and intensive care unit costs compared with usual care patients. Two confirmatory analyses were performed. Including mean costs per day before palliative care and before a comparable reference day for usual care patients in the propensity score models resulted in similar results. Estimating costs for palliative care patients assuming that they did not receive palliative care resulted in projected costs that were not significantly different from usual care costs. Conclusion: Hospital palliative care consultation teams are associated with significant hospital cost savings. C1 [Morrison, R. Sean; Penrod, Joan D.; Litke, Ann; Meier, Diane E.] Mt Sinai Sch Med, Hertzberg Palliat Care Inst, Brookdale Dept Geriatr, New York, NY 10029 USA. [Morrison, R. Sean; Meier, Diane E.] Natl Palliat Care Res Ctr, New York, NY USA. [Morrison, R. Sean; Cassel, J. Brian; Caust-Ellenbogen, Melissa; Spragens, Lynn; Meier, Diane E.] Ctr Adv Palliat Care, New York, NY USA. [Morrison, R. Sean; Penrod, Joan D.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Cassel, J. Brian] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Caust-Ellenbogen, Melissa] Mt Carmel Hlth Syst, Columbus, OH USA. RP Morrison, RS (reprint author), Mt Sinai Sch Med, Hertzberg Palliat Care Inst, Brookdale Dept Geriatr, Box 1070,1 Gustave L Levy Pl, New York, NY 10029 USA. EM sean.morrison@mssm.edu FU Center to Advance Palliative Care; National Palliative Care Research Center; National Institute on Aging [K24 AG022345]; Aetna, Brookdale, John A. Hartford, Jeht, Robert Wood Johnson, Emily Davie and Joseph S. Kornfeld, and Olive Branch Foundations FX This project was supported by the Center to Advance Palliative Care, the National Palliative Care Research Center, and by a Mid-Career Investigator Award in Patient Oriented Research (K24 AG022345) from the National Institute on Aging (Dr Morrison). The Center to Advance Palliative Care and the National Palliative Care Research Center are supported by the Aetna, Brookdale, John A. Hartford, Jeht, Robert Wood Johnson, Emily Davie and Joseph S. Kornfeld, and Olive Branch Foundations. NR 39 TC 301 Z9 303 U1 6 U2 18 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 SEP 8 PY 2008 VL 168 IS 16 BP 1783 EP 1790 DI 10.1001/archinte.168.16.1783 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 345XI UT WOS:000259030600010 PM 18779466 ER PT J AU Jacobson, BC Moy, B Colditz, GA Fuchs, CS AF Jacobson, Brian C. Moy, Beverly Colditz, Graham A. Fuchs, Charles S. TI Postmenopausal hormone use and symptoms of gastroesophageal reflux SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; NITRIC-OXIDE; EROSIVE ESOPHAGITIS; UNITED-STATES; RISK-FACTORS; BODY-MASS; SPHINCTER; DISEASE; WOMEN; QUESTIONNAIRE AB Background: Previous studies suggest that elevated levels of estrogen and progesterone, either through endogenous or exogenous sources, increase gastroesophageal reflux. Methods: To evaluate the relationship between symptoms of gastroesophageal reflux disease (GERD) and postmenopausal hormone (PMH) therapy, including the use of selective estrogen receptor modulators and over-the-counter (OTC) hormone preparations, we performed a prospective cohort study of 51 637 postmenopausal women enrolled in the Nurses' Health Study who provided data on the use of PMH therapy biennially since 1976, and information about symptoms of GERD in 2002. Results: Among eligible participants, 12 018 women (23%) reported GERD symptoms. Compared with women who never used PMHs, the multivariate odds ratio (OR) for the risk of GERD symptoms was 1.46 (95% confidence interval [CI], 1.36-1.56) for past hormone users, 1.66 (95% CI, 1.54-1.79) for current users of estrogen only, and 1.41 (95% CI, 1.29-1.54) for current users of combined estrogen and progesterone. The risk of GERD symptoms increased significantly with increasing estrogen dosage (P < .001) and increasing duration of estrogen use (P < .001). Moreover, current selective estrogen receptor modulator users experienced an OR of 1.39 (95% CI, 1.22-1.59) for GERD symptoms, and women currently using OTC hormone preparations had an OR of 1.37 (95% CI, 1.16-1.62). Conclusions: Postmenopausal use of estrogens, selective estrogen receptor modulators, or OTC hormone preparations is associated with a greater likelihood of symptoms of GERD. This suggests a hormonal component to the pathophysiologic characteristics of GERD in women. C1 [Jacobson, Brian C.] Boston Univ, Boston Med Ctr, Gastroenterol Sect, Boston, MA 02215 USA. [Jacobson, Brian C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Moy, Beverly] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Moy, Beverly; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. RP Jacobson, BC (reprint author), Boston Univ, Med Ctr, Gastroenterol Sect, 88 E Concord St,Room 7721, Boston, MA 02118 USA. EM brian.jacobson@bmc.org RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU National Institute of Diabetes, Digestive, and Kidney Diseases [K08-070706]; National Institutes of Health; Friends of Mel Foundation FX Dr Jacobson is supported by grant K08-070706 from the National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health. Dr Moy is supported by a career development award from the Friends of Mel Foundation. NR 30 TC 10 Z9 10 U1 0 U2 0 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 SEP 8 PY 2008 VL 168 IS 16 BP 1798 EP 1804 DI 10.1001/archinte.168.16.1798 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 345XI UT WOS:000259030600012 PM 18779468 ER PT J AU Van Ness, B Ramos, C Haznadar, M Hoering, A Haessler, J Crowley, J Jacobus, S Oken, M Rajkumar, V Greipp, P Barlogie, B Durie, B Katz, M Atluri, G Fang, G Gupta, R Steinbach, M Kumar, V Mushlin, R Johnson, D Morgan, G AF Van Ness, Brian Ramos, Christine Haznadar, Majda Hoering, Antje Haessler, Jeff Crowley, John Jacobus, Susanna Oken, Martin Rajkumar, Vincent Greipp, Philip Barlogie, Bart Durie, Brian Katz, Michael Atluri, Gowtham Fang, Gang Gupta, Rohit Steinbach, Michael Kumar, Vipin Mushlin, Richard Johnson, David Morgan, Gareth TI Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival SO BMC MEDICINE LA English DT Article ID MULTIPLE-MYELOMA; STANDARD CHEMOTHERAPY; ENDOTHELIAL-CELLS; EXPRESSION; SEQUENCE; DATABASE; GENES; TRIAL; POLYMORPHISMS; ANGIOGENESIS AB Background: We have engaged in an international program designated the Bank On A Cure, which has established DNA banks from multiple cooperative and institutional clinical trials, and a platform for examining the association of genetic variations with disease risk and outcomes in multiple myeloma. We describe the development and content of a novel custom SNP panel that contains 3404 SNPs in 983 genes, representing cellular functions and pathways that may influence disease severity at diagnosis, toxicity, progression or other treatment outcomes. A systematic search of national databases was used to identify non-synonymous coding SNPs and SNPs within transcriptional regulatory regions. To explore SNP associations with PFS we compared SNP profiles of short term (less than 1 year, n = 70) versus long term progression-free survivors (greater than 3 years, n = 73) in two phase III clinical trials. Results: Quality controls were established, demonstrating an accurate and robust screening panel for genetic variations, and some initial racial comparisons of allelic variation were done. A variety of analytical approaches, including machine learning tools for data mining and recursive partitioning analyses, demonstrated predictive value of the SNP panel in survival. While the entire SNP panel showed genotype predictive association with PFS, some SNP subsets were identified within drug response, cellular signaling and cell cycle genes. Conclusion: A targeted gene approach was undertaken to develop an SNP panel that can test for associations with clinical outcomes in myeloma. The initial analysis provided some predictive power, demonstrating that genetic variations in the myeloma patient population may influence PFS. C1 [Van Ness, Brian; Ramos, Christine; Haznadar, Majda] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. [Jacobus, Susanna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oken, Martin] N Mem Hosp, Minneapolis, MN USA. [Rajkumar, Vincent; Greipp, Philip] Mayo Clin, Rochester, MN USA. [Barlogie, Bart] Univ Arkansas, Med Sci Ctr, Little Rock, AR USA. [Durie, Brian] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Katz, Michael] Int Myeloma Fdn, Hollywood, CA USA. [Mushlin, Richard] IBM Res Corp, TJ Watson Res Ctr, Yorktown Hts, NY USA. [Johnson, David; Morgan, Gareth] Royal Marsden Hosp, London SW3 6JJ, England. RP Van Ness, B (reprint author), Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. EM vanne001@umn.edu; ramos005@umn.edu; hazna001@umn.edu; antjeh@crab.org; jeffh@crab.org; johnc@crab.org; jacobus@jimmy.harvard.edu; travelermmo@yahoo.com; rajkumar.vincent@mayo.edu; greipp.philip@mayo.edu; BarlogieBarthel@exchange.uams.edu; bdurie@aptiumoncology.com; katz_mike@bah.com; atlur005@umn.edu; gangfang@cs.umn.edu; rohit@cs.umn.edu; steinbac@cs.umn.edu; kumar@cs.umn.edu; mushlin@us.ibm.com; David.Johnson@icr.ac.uk; Gareth.Morgan@icr.ac.uk RI Johnson, David/A-3907-2011; OI Johnson, David/0000-0003-0887-3343; Rajkumar, S. Vincent/0000-0002-5862-1833 FU International Myeloma Foundation; National Institutes of Health [PO1 CA62242, 5U10CA038926]; NSF [CNS-0551551] FX This work was supported by the International Myeloma Foundation; a grant from the National Institutes of Health to the Eastern Cooperative Oncology Group PO1 CA62242 (to BVN) and the Southwest Oncology Group 5U10CA038926 (to JC); and NSF Grant CNS-0551551 (to VK). NR 41 TC 33 Z9 33 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD SEP 8 PY 2008 VL 6 AR 26 DI 10.1186/1741-7015-6-26 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 357AF UT WOS:000259818000001 PM 18778477 ER PT J AU Kulkarni, H Agan, BK Marconi, VC O'Connell, RJ Camargo, JF He, WJ Delmar, J Phelps, KR Crawford, G Clark, RA Dolan, MJ Ahuja, SK AF Kulkarni, Hemant Agan, Brian K. Marconi, Vincent C. O'Connell, Robert J. Camargo, Jose F. He, Weijing Delmar, Judith Phelps, Kenneth R. Crawford, George Clark, Robert A. Dolan, Matthew J. Ahuja, Sunil K. TI CCL3L1-CCR5 Genotype Improves the Assessment of AIDS Risk in HIV-1-Infected Individuals SO PLOS ONE LA English DT Article AB Background: Whether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy ( HAART) during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4(+) T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk. Methods and Findings: In a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group (GRG) based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1-CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV(+) subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree (CART) analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4(+) cell count thresholds used to guide HAART initiation. Conclusions: The combination of the laboratory and genetic markers captures a broader spectrum of AIDS risk than either marker alone. By tracking a unique aspect of AIDS risk distinct from that captured by the laboratory parameters, CCL3L1-CCR5 genotypes may have utility in HIV clinical management. These findings illustrate how genomic information might be applied to achieve practical benefits of personalized medicine. C1 [Kulkarni, Hemant; Camargo, Jose F.; He, Weijing; Crawford, George; Clark, Robert A.; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX USA. [Kulkarni, Hemant; Camargo, Jose F.; He, Weijing; Ahuja, Sunil K.] Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX USA. [Agan, Brian K.; Marconi, Vincent C.; O'Connell, Robert J.; Delmar, Judith; Dolan, Matthew J.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD USA. [Agan, Brian K.; Marconi, Vincent C.; O'Connell, Robert J.; Delmar, Judith; Dolan, Matthew J.] Wilford Hall United States Air Force Med Ctr, Infect Dis Serv, Lackland AFB, TX USA. [Agan, Brian K.; Dolan, Matthew J.] Wilford Hall United States Air Force Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX USA. [Agan, Brian K.; Marconi, Vincent C.; Delmar, Judith; Dolan, Matthew J.] San Antonio Mil Med Ctr, Ft Sam Houston, TX USA. [Phelps, Kenneth R.] Stratton Veterans Affairs Med Ctr, Albany, NY USA. [Phelps, Kenneth R.] Albany Med Coll, Albany, NY USA. [Ahuja, Sunil K.] Univ Texas, Hlth Sci Ctr, Dept Microbiol & Immunol & Biochem, San Antonio, TX USA. RP Kulkarni, H (reprint author), S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX USA. EM mdolan@idcrp.org; ahujas@uthscsa.edu RI Marconi, Vincent/N-3210-2014; OI Marconi, Vincent/0000-0001-8409-4689; Agan, Brian/0000-0002-5114-1669 FU Veterans Administration (VA) Center on AIDS and HIV infection of the South Texas Veterans Health Care System; MERIT [R37046326]; NIH [AI043279, MH069270]; Elizabeth Glaser Scientist Award; Burroughs Wellcome Clinical Scientist Award in Translational Research; Infectious Disease Clinical Research Program (IDCRP) of the Uniformed Services University of the Health Sciences (USUHS); HHS/NIH/NIAID/DCR [HU0001-05-2-0011] FX This work was supported by the Veterans Administration (VA) Center on AIDS and HIV infection of the South Texas Veterans Health Care System, and a MERIT (R37046326) and other awards (AI043279 and MH069270) from the NIH to S.K.A. S.K.A. is a recipient of the Elizabeth Glaser Scientist Award and the Burroughs Wellcome Clinical Scientist Award in Translational Research. Support for the Wilford Hall Medical Center cohort was provided by the Infectious Disease Clinical Research Program (IDCRP) of the Uniformed Services University of the Health Sciences (USUHS), of which the Tri-Service AIDS Clinical Consortium (TACC) is a component. The IDCRP is a Department of Defense tri-service program executed through USUHS and the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), in collaboration with HHS/NIH/NIAID/DCR through Interagency Agreement HU0001-05-2-0011. The authors have no commercial or other association that might pose a conflict of interest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 92 TC 16 Z9 16 U1 1 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 SEP 8 PY 2008 VL 3 IS 9 AR e3165 DI 10.1371/journal.pone.0003165 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 422JQ UT WOS:000264424300009 PM 18776933 ER PT J AU Jarlskog, CZ Paganetti, H AF Jarlskog, Christina Zacharatou Paganetti, Harald TI Sensitivity of different dose scoring methods on organ-specific neutron dose calculations in proton therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BIOL-PHYS 2006/65/1-7; MONTE-CARLO; RADIATION-THERAPY; SECONDARY NEUTRON; EQUIVALENT; RADIOTHERAPY; SIMULATION; PHANTOMS; TOOLKIT; MOTHER AB Scattered doses, e. g. neutron doses in proton therapy, are of concern in radiation therapy. Although measured data are the gold standard, Monte Carlo simulations allow a more realistic consideration of patient anatomy via whole-body phantoms. When calculating neutron doses with Monte Carlo techniques, the dose can be scored in different ways because neutrons deposit dose indirectly. The purpose of this study was to assess the differences in neutron dose predictions when using different dose scoring methods. Two methods were tested. In the first method, the organ dose was calculated by accumulating dose from each individual dose deposition event with a particle-specific radiation weighting factor applied. Alternatively, we applied a method where the calculation was done by averaging the dose over the total number of events irrespective of particle type and applying average neutron radiation weighting factors. In addition, we assessed the sensitivity of different neutron quality factor assignments based on two recommendations by the International Commission on Radiological Protection (ICRP). We found that the scoring procedure can lead to differences in the organ equivalent dose of about 25%. As to the ICRP definition of neutron quality factors, the most recent recommendation results in about 10% higher organ doses. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jarlskog, CZ (reprint author), Univ Copenhagen Hosp, Rigshosp, Dept Radiat Oncol, DK-2100 Copenhagen, Denmark. FU National Institutes of Health [R01 CA 116743] FX This work was supported by National Institutes of Health (R01 CA 116743). NR 25 TC 10 Z9 10 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 7 PY 2008 VL 53 IS 17 BP 4523 EP 4532 DI 10.1088/0031-9155/53/17/004 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 338VH UT WOS:000258537000005 PM 18677040 ER PT J AU Paganetti, H Jiang, HY Parodi, K Slopsema, R Engelsman, M AF Paganetti, Harald Jiang, Hongyu Parodi, Katia Slopsema, Roelf Engelsman, Martijn TI Clinical implementation of full Monte Carlo dose calculation in proton beam therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BRAGG PEAK FIELDS; TIME-DEPENDENT GEOMETRIES; MULTIPLE SOURCE MODEL; NUCLEAR-INTERACTIONS; ELECTRON-TRANSPORT; RADIATION-THERAPY; STOPPING-POWER; PHOTON BEAMS; SIMULATION; GEANT4 AB The goal of this work was to facilitate the clinical use of Monte Carlo proton dose calculation to support routine treatment planning and delivery. The Monte Carlo code Geant4 was used to simulate the treatment head setup, including a time-dependent simulation of modulator wheels (for broad beam modulation) and magnetic field settings (for beam scanning). Any patient-field-specific setup can be modeled according to the treatment control system of the facility. The code was benchmarked against phantom measurements. Using a simulation of the ionization chamber reading in the treatment head allows the Monte Carlo dose to be specified in absolute units (Gy per ionization chamber reading). Next, the capability of reading CT data information was implemented into the Monte Carlo code to model patient anatomy. To allow time-efficient dose calculation, the standard Geant4 tracking algorithm was modified. Finally, a software link of the Monte Carlo dose engine to the patient database and the commercial planning system was established to allow data exchange, thus completing the implementation of the proton Monte Carlo dose calculation engine ('DoC++'). Monte Carlo re-calculated plans are a valuable tool to revisit decisions in the planning process. Identification of clinically significant differences between Monte Carlo and pencil-beam-based dose calculations may also drive improvements of current pencil-beam methods. As an example, four patients (29 fields in total) with tumors in the head and neck regions were analyzed. Differences between the pencil-beam algorithm and Monte Carlo were identified in particular near the end of range, both due to dose degradation and overall differences in range prediction due to bony anatomy in the beam path. Further, the Monte Carlo reports dose-to-tissue as compared to dose-to-water by the planning system. Our implementation is tailored to a specific Monte Carlo code and the treatment planning system XiO (Computerized Medical Systems Inc.). However, this work describes the general challenges and considerations when implementing proton Monte Carlo dose calculation in a clinical environment. The presented solutions can be easily adopted for other planning systems or other Monte Carlo codes. C1 [Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU National Institutes of Health [5 P01 CA21239-25] FX We would like to thank Sashidar Kollipara, Tom Madden and Andrew Kaplan for their help in dealing with converting data formats, providing software for analysis and taking care of computer hardware management. Further, we would like to thank Christina Zacharatou Jarlskog for her (separately published) work on the Geant4 physics setup. We would also like to thank Joseph Perl (SLAC) from the Geant4 collaboration for answering many questions. Drs Chan, Liebsch and Loeffler provided the patient data used in this study. Treatment planning was done by Judy Adams. This work was supported in part by National Institutes of Health (5 P01 CA21239-25). NR 59 TC 117 Z9 117 U1 0 U2 22 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 7 PY 2008 VL 53 IS 17 BP 4825 EP 4853 DI 10.1088/0031-9155/53/17/023 PG 29 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 338VH UT WOS:000258537000024 PM 18701772 ER PT J AU Sugimoto, K AF Sugimoto, Ken TI Role of STAT3 in inflammatory bowel disease SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE inflammatory bowel disease; STAT3; inflammation; innate immunity; acquired immunity ID ACTIVE CROHNS-DISEASE; RECOMBINANT HUMAN INTERLEUKIN-11; INTESTINAL EPITHELIAL-CELLS; CD4(+) T-CELLS; SIGNAL TRANSDUCERS; MUCOSAL IMMUNITY; INNATE IMMUNITY; GROWTH-HORMONE; ANIMAL-MODELS; MICE AB Signal transducers and activators of transcription 3 (STAT3) play an important role in various autoimmune disorders including inflammatory bowel disease (IBD). Recent studies have revealed that STAT3 activation plays distinctly different roles between innate immune responses and acquired immune responses in colitis. STAT3-mediated activation of acquired immune responses plays a pathogenic role in colitis by enhancing the survival of pathogenic T cells. In contrast, STAT3-mediated activation of innate responses contributes to the suppression of colitis. This review will summarize the current understanding of the roles of STAT3 in IBD and the potential of targeting STAT3 for the treatment of IBD, emphasizing recent observations. (c) 2008 The WIG Press. All rights reserved. C1 [Sugimoto, Ken] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Sugimoto, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM sugiken@jg8.so-net.ne.jp NR 59 TC 32 Z9 35 U1 1 U2 5 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD SEP 7 PY 2008 VL 14 IS 33 BP 5110 EP 5114 DI 10.3748/wjg.14.5110 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 346TB UT WOS:000259091000002 PM 18777586 ER PT J AU Wang, LJ Cao, Y Shi, HN AF Wang, Li Jian Cao, Yue Shi, Hai Ning TI Helminth infections and intestinal inflammation SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE helminths; innate and adaptive immunity; intestinal inflammation ID REGULATORY T-CELLS; ALTERNATIVELY ACTIVATED MACROPHAGES; IMMUNOLOGICAL SELF-TOLERANCE; NEGLECTED TROPICAL DISEASES; ANTIGEN-PRESENTING CELLS; GROWTH-FACTOR-BETA; DENDRITIC CELLS; CITROBACTER-RODENTIUM; IMMUNE-RESPONSES; INDUCED COLITIS AB Evidence from epidemiological studies indicates an inverse correlation between the incidence of certain immune-mediated diseases, including inflammatory bowel diseases (IBD), and exposure to helminths. Helminth parasites are the classic inducers of Th2 responses. The Th2-polarized T cell response driven by helminth infection has been linked to the attenuation of some damaging Th1 driven inflammatory responses, preventing some Th1-mediated autoimmune diseases in the host, including experimentally induced colitis. Helminth parasites (the porcine whipworm, Trichurisuis have been tested for treating IBD patients, resulting in clinical amelioration of the disease. As a result, there is a great deal of interest in the research community in exploring the therapeutic use of helminth parasites for the control of immune-mediated diseases, including IBD. However, recent studies have provided evidence indicating the exacerbating effects of helminths on bacterial as well as non-infectious colitis in animal models. Therefore, a better understanding of mechanisms by which helminths modulate host immune responses in the gut may reveal novel, more effective and safer approaches to helminth-based therapy of IBD. C1 [Wang, Li Jian; Cao, Yue; Shi, Hai Ning] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Wang, Li Jian; Cao, Yue; Shi, Hai Ning] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Shi, HN (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, Bldg 114 16th St,Room 3504, Charlestown, MA 02129 USA. EM shiha@helix.mgh.harvard.edu FU NIDDK NIH HHS [R21 DK 074727, R21 DK074727] NR 91 TC 28 Z9 32 U1 2 U2 6 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD SEP 7 PY 2008 VL 14 IS 33 BP 5125 EP 5132 DI 10.3748/wjg.14.5125 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 346TB UT WOS:000259091000004 PM 18777588 ER PT J AU Hokama, A Mizoguchi, E Mizoguchi, A AF Hokama, Akira Mizoguchi, Emiko Mizoguchi, Atsushi TI Roles of galectins in inflammatory bowel disease SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE galectin; inflammatory bowel disease; Crohn's disease; ulcerative colitis; pathogenesis; apoptosis; glycosylation ID ALPHA MUTANT MICE; T-CELL DEATH; GLYCAN-BINDING PROTEINS; NF-KAPPA-B; INTESTINAL INFLAMMATION; CHRONIC COLITIS; ULCERATIVE-COLITIS; TUMOR PROGRESSION; MESSENGER-RNA; ANIMAL-MODELS AB Protein/carbohydrate interactions through specific protein families termed lectin control essential biological processes. Galectins, a family of animal lectins defined by shared amino acid sequence with affinity for beta-galactosides, appear to be functionally polyvalent in a wide range of biological activity. Recent studies have identified immunoregulatory roles of galectins in intestinal inflammatory disorders. Galectin-1 and galectin -2 contribute to the suppression of intestinal inflammation by the induction of apoptosis of activated T cells, whereas galectin-4 is involved in the exacerbation of this inflammation by specifically stimulating intestinal CD4+ T cells to produce IL-6. We review how different members of the galectins provide inhibitory or stimulatory signals to control intestinal immune response under intestinal inflammation. (c) 2008 The WJG Press. All rights reserved. C1 [Hokama, Akira] Univ Ryukyus, Fac Med, Dept Med & Therapeut, Dept Internal Med 1, Okinawa 9030215, Japan. [Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Study Inflammatory Bowel Dis, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. [Mizoguchi, Atsushi] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Expt Pathol Unit, Dept Pathol,Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Hokama, A (reprint author), Univ Ryukyus, Fac Med, Dept Med & Therapeut, Dept Internal Med 1, 207 Uehara, Okinawa 9030215, Japan. EM hokama-a@med.u-ryukyu.ac.jp FU NIDDK NIH HHS [DK64289, DK64351, DK74454, K08 DK064289, R01 DK064351, R03 DK074454] NR 63 TC 19 Z9 20 U1 0 U2 2 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD SEP 7 PY 2008 VL 14 IS 33 BP 5133 EP 5137 DI 10.3748/wjg.14.5133 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 346TB UT WOS:000259091000005 PM 18777589 ER PT J AU Sugimoto, M Furuta, T Nakamura, A Shirai, N Ikuma, M Misaka, S Uchida, S Watanabe, H Ohashi, K Ishizaki, T Hishida, A AF Sugimoto, Mitsushige Furuta, Takahisa Nakamura, Akiko Shirai, Naohito Ikuma, Mutsuhiro Misaka, Shingen Uchida, Shinya Watanabe, Hiroshi Ohashi, Kyoichi Ishizaki, Takashi Hishida, Akira TI Maintenance time of sedative effects after an intravenous infusion of diazepam: A guide for endoscopy using diazepam SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE diazepam; sedation; cytochrome P450 (CYP) 2C19; endoscopy; complication; critical flicker fusion test; eye movement analysis; postural sway test; visual analog scale ID N-DESMETHYLDIAZEPAM; CYP2C19 GENOTYPE; PLASMA-LEVELS; IN-VIVO; METABOLISM; OMEPRAZOLE; PHARMACOKINETICS; SCHIZOPHRENIA; DISPOSITION; POLYMORPHISM AB AIM: To examine whether the sedative effects assessed by psychomotor tests would depend on the cytochrome P450 (CYP) 2C19 genotypes after an infusion regimen of diazepam commonly used for gastrointestinal endoscopy in Japan. METHODS: Fifteen healthy Japanese volunteers consisting of three different CYP2C19 genotype groups underwent a critical flicker fusion test, an eye movement analysis and a postural sway test as a test for physical sedative effects, and a visual analog scale (VAS) symptom assessment method as a test for mental sedative effects during the 336 h period after the intravenous infusion of diazepam (5 mg). RESULTS: The physical sedative effects assessed by the critical flicker test continued for 1 h (t values of 5 min, 30 min and 60 min later: 4.35, 5.00 and 3.19, respectively) and those by the moving radial area of a postural sway test continued for 3 h (t values of 5 h, 30 h, 60 min and 3 h later: -4.05, -3.42, -2.17 and -2.58, respectively), which changed significantly compared with the baseline level before infusion (P < 0.05). On the other hand, the mental sedative effects by the VAS method improved within 1 h. The CYP2C19 genotype-dependent differences in the postinfusion sedative effects were not observed in any of the four psychomotor function tests. CONCLUSION: With the psychomotor tests, the objective sedative effects of diazepam continued for 1 h to 3 h irrespective of CYP2C19 genotype status and the subjective sedative symptoms improved within I h. Up to 3 h of clinical care appears to be required after the infusion of diazepam, although patients feel subjectively improved. (c) 2008 The WJG Press. All rights reserved. C1 [Sugimoto, Mitsushige; Nakamura, Akiko; Ikuma, Mutsuhiro; Hishida, Akira] Hamamatsu Univ Sch Med, Dept Med 1, Higashi Ku, Hamamatsu, Shizuoka 4313192, Japan. [Furuta, Takahisa] Hamamatsu Univ Sch Med, Clin Res Ctr, Hamamatsu, Shizuoka 4313192, Japan. [Shirai, Naohito] Enshu Gen Hosp, Dept Gastroenterol, Naka Ku, Hamamatsu, Shizuoka 4300929, Japan. [Misaka, Shingen; Uchida, Shinya] Univ Shizuoka, Sch Pharmaceut Sci, Dept Pharmacokinet & Pharmacodynam, Suruga Ku, Shizuoka 4228526, Japan. [Watanabe, Hiroshi; Ishizaki, Takashi] Hamamatsu Univ Sch Med, Dept Clin Pharmacol & Therapeut, Higashi Ku, Hamamatsu, Shizuoka 4313192, Japan. [Ohashi, Kyoichi] Oita Univ, Dept Clin Pharmacol & Therapeut, Hazama, Yufu 8795593, Japan. RP Sugimoto, M (reprint author), Hamamatsu Univ Sch Med, Dept Med 1, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM sugimoto@bcm.edu NR 38 TC 1 Z9 1 U1 2 U2 3 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD SEP 7 PY 2008 VL 14 IS 33 BP 5197 EP 5203 DI 10.3748/wjg.14.5197 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 346TB UT WOS:000259091000013 PM 18777597 ER PT J AU Mexal, S Berger, R Pearce, L Barton, A Logel, J Adams, CE Ross, RG Freedman, R Leonard, S AF Mexal, Sharon Berger, Ralph Pearce, Lucy Barton, Amanda Logel, Judy Adams, Catherine E. Ross, Randal G. Freedman, Robert Leonard, Sherry TI Regulation of a novel alpha N-catenin splice variant in schizophrenic smokers SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; nicotine addiction; CTNNA2; evolution; primate ID CELL-ADHESION; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; BIPOLAR DISORDER; GENE-EXPRESSION; GENOME; EVOLUTION; CADHERIN; ORGANIZATION; METAANALYSIS AB The alpha N-catenin (CTNNA2) gene represents a promising candidate gene for schizophrenia based upon previous genetic linkage, expression, and mouse knockout studies. CTNNA2 is differentially regulated by smoking in schizophrenic patients. In this report, the genomic structure of a primate-specific alpha N-catenin splice variant (alpha N-catenin III) is described. A comparison of alpha N-catenin III mRNA expression across postmortem hippocampi from schizophrenic and non-mentally ill smokers and non-smokers revealed a significant decrease in expression among patient non-smokers compared to all other groups. The recent evolutionary divergence of this gene, as well as the differences in gene expression in postmortem brain of schizophrenic non-smokers, supports the role of alpha N-catenin III as a novel disease susceptibility gene. (c) 2007 Wiley-Liss, Inc. C1 [Berger, Ralph; Pearce, Lucy; Barton, Amanda; Logel, Judy; Adams, Catherine E.; Ross, Randal G.; Freedman, Robert; Leonard, Sherry] Univ Colorado Denver, Dept Psychiat, Aurora, CO 80045 USA. [Berger, Ralph; Pearce, Lucy; Barton, Amanda; Logel, Judy; Adams, Catherine E.; Ross, Randal G.; Freedman, Robert; Leonard, Sherry] Hlth Sci Ctr, Aurora, CO USA. [Mexal, Sharon] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Adams, Catherine E.; Freedman, Robert; Leonard, Sherry] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Leonard, S (reprint author), Univ Colorado Denver, Dept Psychiat, Mailstop 8344,POB 6511, Aurora, CO 80045 USA. EM sherry.leonard@uchsc.edu RI Barton, Anne/N-2053-2014 OI Barton, Anne/0000-0003-3316-2527 FU Veterans Affairs Medical Research Service; NIH [DA09457, MH81177] FX Grant sponsor: Veterans Affairs Medical Research Service; Grant sponsor: NIH; Grant numbers: DA09457, MH81177. NR 39 TC 15 Z9 16 U1 0 U2 0 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 SEP 5 PY 2008 VL 147B IS 6 BP 759 EP 768 DI 10.1002/ajmg.b.30679 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 346EB UT WOS:000259050100014 PM 18163523 ER PT J AU Dickson, MR Li, J Wiener, HW Perry, RT Blacker, D Bassett, SS Go, RCP AF Dickson, M. Ryan Li, Jian Wiener, Howard W. Perry, Rodney T. Blacker, Deborah Bassett, Susan S. Go, Rodney C. P. TI A genomic scan for age at onset of Alzheimer's disease in 437 families from the NIMH genetic initiative SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE Alzhiemer's disease; censored quantitative trait; variance-component linkage analysis ID ALPHA-T-CATENIN; VARIANCE-COMPONENTS ANALYSIS; APOLIPOPROTEIN-E; LINKAGE ANALYSIS; CHROMOSOME 12; SUSCEPTIBILITY GENES; CACHE COUNTY; AT-ONSET; OF-ONSET; PEDIGREES AB We performed linkage analysis for age at onset (AAO) in the total Alzheimer's disease (AD) NIMH sample (N = 437 families). Families were subset as late-onset (320 families, AAO >= 65) and early/mixed (117 families, at least 1 member with 50 < AAO < 65). Treating AAO as a censored trait, we obtained the gender and APOE adjusted residuals in a parametric survival model and analyzed the residuals as the quantitative trait (QT) in variance-component linkage analysis. For comparison, AAO-age at exam (AAE) was analyzed as the QT adjusting for affection status, gender, and APOE. Heritabilities for residual and AAO-AAE outcomes were 66.3% and 74.0%, respectively for the total sample, 56.0% and 57.0% in the late-onset sample, and 33.0% for both models in the early/mixed sample. The residual model yielded the largest peaks on chromosome 1 with LOD = 2.0 at 190 cM in the total set, LOD 1.7 at 116 cM on chromosome 3 in the early/mixed subset, and LOD = 1.4 at 71 and 86 cM, respectively, on chromosome 6 in the late-onset subset. For the AAO-AAE outcome model the largest peaks were identified on chromosome 1 at 137 cM (LOD = 2.8) and chromosome 6 at 69 cM (LOD = 2.3) and 86 cM (LOD = 2.2) all in the late-onset subset. Additional peaks with LOD >= 1 were identified on chromosomes 1, 2, 3, 6, 8, 9, 10, and 12 for the total sample and each subset. Results replicate previous findings, but identify additional suggestive peaks indicating the genetics of AAO in AD is complex with many chromosomal regions potentially containing modifying genes. (c) 2008 Wiley-Liss, Inc. C1 [Dickson, M. Ryan; Li, Jian; Wiener, Howard W.; Perry, Rodney T.; Go, Rodney C. P.] Univ Alabama, Dept Epidemiol & Int Hlth, Birmingham, AL 35294 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Gerontol Res Unit, Charlestown, MA USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bassett, Susan S.] Johns Hopkins Univ, Inst Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Dickson, MR (reprint author), Univ Alabama, Dept Epidemiol, Ryals 230N,1665 Univ Blvd, Birmingham, AL 35294 USA. EM dicksonr@uab.edu FU Massachusetts General Hospital, Boston, MA [U01 MH46281]; Johns Hopkins University, Baltimore, MD [U01 MH46290]; University of Alabama at Birmingham, Birmingham, AL [U01 MH46373] FX Grant sponsor: Massachusetts General Hospital, Boston, MA; Grant number: U01 MH46281; Grant sponsor: Johns Hopkins University, Baltimore, MD; Grant number: U01 MH46290; Grant sponsor: University of Alabama at Birmingham, Birmingham, AL; Grant number: U01 MH46373. NR 50 TC 10 Z9 10 U1 1 U2 2 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 SEP 5 PY 2008 VL 147B IS 6 BP 784 EP 792 DI 10.1002/ajmg.b.30689 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 346EB UT WOS:000259050100017 PM 18189239 ER PT J AU Huang, CH Santangelo, SL AF Huang, Christine H. Santangelo, Susan L. TI Autism and serotonin transporter gene polymorphisms: A systematic review and meta-analysis SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE autism; SLC6A4; 5-HTTLPR; STin2 VNTR; meta-analysis; serotonin ID WHOLE-BLOOD SEROTONIN; RIGID-COMPULSIVE BEHAVIORS; PROMOTER VARIANTS; PLATELET SEROTONIN; LINKAGE DISEQUILIBRIUM; ASSOCIATION ANALYSIS; DOUBLE-BLIND; DISORDER; SLC6A4; REGION AB The serotonin transporter gene (5-HTT) plays a crucial role in serotonergic neurotransmission and has been found to be associated, with varying degrees of significance, with many diseases, including autism. Prior association studies of autism have yielded conflicting results regarding the association between two common 5-HTT polymorphisms, the promoter insertion/deletion (5HTTLPR) and the intron 2 VNTR (STin2 VNTR). We conducted a systematic review and meta-analysis to test the following hypotheses: (i) there is an association between autism and either or both of the 5-HTTLPR and STin2 VNTR polymorphisms, and (ii) the S allele of 5-HTTLPR and/or the STin2.12 allele of the VNTR are the specific risk alleles for autism. All published family-based and population based studies were examined to determine the overall strength of association between 5-HTT polymorphisms and autism. After exclusion of studies with overlapping samples and studies whose data did not allow for calculation of an odds ratio, 16 studies were included for final analyses, all but two of which used a family-based design. The meta-analysis failed to find a significant overall association between either of the 5-HTT polymorphisms examined and autism. Further, no allelic transmission distortion was found when studies of simplex (11 studies) and multiplex (3 studies) family samples were analyzed separately. However, there was significant heterogeneity by ethnicity; family based studies of US mixed population samples showed preferential transmission of the S allele of 5-HTTLPR (S allele:L allele = 247:183), while there was no allelic distortion among the family-based studies of European and Asian samples. (c) 2008 Wiley-Liss, Inc. C1 [Huang, Christine H.; Santangelo, Susan L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Huang, Christine H.; Santangelo, Susan L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Santangelo, Susan L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Santangelo, SL (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, 185 Cambridge St,CPZN 6-256, Boston, MA 02114 USA. EM ssantangelo@pngu.mgh.harvard.edu FU NLM Family Foundation FX The authors are grateful to the NLM Family Foundation for their support. We are grateful to Dr. Ed Cook and Dr. Jim Sutcliffe for their helpful discussions of an earlier draft of this article and thank Ms. Yu-Chun Yen for her help in preparing the paper. NR 71 TC 58 Z9 63 U1 5 U2 11 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 SEP 5 PY 2008 VL 147B IS 6 BP 903 EP 913 DI 10.1002/ajmg.b.30720 PG 11 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 346EB UT WOS:000259050100032 PM 18286633 ER PT J AU Roffman, JL Weiss, AP Deckersbach, T Freudenreich, O Henderson, DC Wong, DH Halsted, CH Goff, DC AF Roffman, Joshua L. Weiss, Anthony P. Deckersbach, Thilo Freudenreich, Oliver Henderson, David C. Wong, Donna H. Halsted, Charles H. Goff, Donald C. TI Interactive effects of COMT Val108/158Met and MTHFR C677T on executive function in schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; executive function; COMT; MTHFR; methylation ID CATECHOL-O-METHYLTRANSFERASE; CARD SORTING TEST; VAL(108/158) MET GENOTYPE; FRONTAL-LOBE FUNCTION; METHYLENETETRAHYDROFOLATE REDUCTASE; WORKING-MEMORY; GENETIC-VARIATION; DNA METHYLATION; COMMON MUTATION; HUMAN BRAIN AB Schizophrenia is characterized by heritable deficits in executive function. Two common, functional polymorphisms, catechol-O-methyltransferase (COMT) Val108/158Met and methylenetetrahydrofolate reductase (MTHFR) C677T, have separately been associated with executive function performance in schizophrenia. Given the closely related biochemistry of MTHFR and COMT, it is plausible that the T and Val alleles act synergistically to impair executive function. This investigation of 185 outpatients with schizophrenia examined the interactive effects of these two polymorphisms on Wisconsin Card Sorting Task (WCST) performance. Two WCST measures consistently associated with schizophrenia, perseverative errors and inability to generate categories, were contrasted among compound COMT-MTHFR genotype groups. Individuals homozygous for the COMT Val allele who also carried at least one copy of the MTHFR T allele exhibited a significantly higher percentage of perseverative errors than patients in the other genotype groups. While the T allele also exerted a negative effect on category generation, COMT genotype did not contribute to category performance. It is plausible that cumulative effects of the MTHFR T and COMT Val alleles on intracellular methylation profiles and prefrontal dopamine transmission underlie their interactive effect on perseverative errors. (c) 2008 Wiley-Liss, Inc. C1 [Roffman, Joshua L.; Weiss, Anthony P.; Deckersbach, Thilo; Freudenreich, Oliver; Henderson, David C.; Goff, Donald C.] Massachusetts Gen Hosp, Dept Psychiat, Schizophrenia Program, Charlestown, MA 02139 USA. [Roffman, Joshua L.; Weiss, Anthony P.; Deckersbach, Thilo; Freudenreich, Oliver; Henderson, David C.; Goff, Donald C.] Harvard Univ, Sch Med, Charlestown, MA USA. [Wong, Donna H.; Halsted, Charles H.] Univ Calif Davis, Dept Internal Med & Nutr, Davis, CA 95616 USA. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Schizophrenia Program, 149 13th St,Room 2656, Charlestown, MA 02139 USA. EM jroffman@partners.org FU NIH [MH02025-01A3, MH60450, DK56085]; Harvard Medical School Dupont Warren Fellowship FX This work was supported by NIH grants MH02025-01A3, MH60450 (D.C.G.) and DK56085 (C.H.H.) as well as by the Harvard Medical School Dupont Warren Fellowship (J.L.R.). We thank Dr. Eric Morrow for his helpful comments on the manuscript. NR 46 TC 37 Z9 39 U1 0 U2 2 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 SEP 5 PY 2008 VL 147B IS 6 BP 990 EP 995 DI 10.1002/ajmg.b.30684 PG 6 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 346EB UT WOS:000259050100045 PM 18186041 ER PT J AU Liang, KY Wang, Y Shugart, YY Grados, M Fyer, AJ Rauch, S Murphy, D McCracken, J Rasmussen, S Cullen, B Hoehn-Saric, R Greenberg, B Pinto, A Knowles, J Piacentini, J Pauls, D Bienvenu, O Riddle, M Samuels, J Nestadt, G AF Liang, Kung-Yee Wang, Ying Shugart, Yin Yao Grados, Marco Fyer, Abby J. Rauch, Scott Murphy, Dennis McCracken, James Rasmussen, Steven Cullen, Bernadette Hoehn-Saric, Rudolf Greenberg, Benjamin Pinto, Anthony Knowles, James Piacentini, John Pauls, David Bienvenu, O. Riddle, Mark Samuels, Jack Nestadt, Gerald TI Evidence for potential relationship between SLC1A1 and a putative genetic linkage region on chromosome 14q to obsessive-compulsive disorder with compulsive hoarding SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE OCD; linkage; compulsive hoarding; epistasis; SLC1A1 ID OCD COLLABORATIVE GENETICS; FAMILIES AB Obsessive-compulsive disorder (OCD) is likely a disorder involving complex genetic transmission. This suggests that multiple genetic and environmental factors are involved in its etiology. This is complicated further by the probability of genetic heterogeneity for this phenotype. In this report, we describe a preliminary approach to deal with both complexities. SLC1A1, a glutamate transporter gene on chromosome 9p, was originally proposed to be related to OCD based on two linkage studies, and subsequently association of OCD to the gene has been replicated. Additionally, genetic linkage to a subtype of OCD, compulsive hoarding, has been reported on chromosome 14q. We hypothesized that both genomic regions contribute to OCD in some instances. Using the analytic program GENEFINDER we found that conditioning linkage on chromosome 14q to a marker adjacent to SLC1A1, reduced the size of the linkage region on chromosome 14q and provided evidence for interaction between the regions on chromosomes 9p and 14q. (c) 2008 Wiley-Liss, Inc. C1 [Liang, Kung-Yee] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Wang, Ying; Grados, Marco; Cullen, Bernadette; Hoehn-Saric, Rudolf; Bienvenu, O.; Riddle, Mark; Samuels, Jack; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Shugart, Yin Yao] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Fyer, Abby J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Rauch, Scott] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Murphy, Dennis] NIMH, Bethesda, MD 20892 USA. [McCracken, James] Univ Calif Los Angeles, Los Angeles, CA USA. [Rasmussen, Steven] Brown Univ, Dept Psychiat, Providence, RI USA. [Knowles, James] Univ So Calif, Dept Child Psychiat, Los Angeles, CA USA. RP Nestadt, G (reprint author), Meyer 109,600 N Wolfe St, Baltimore, MD 21287 USA. EM gnestadt@jhmi.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU National Institute of Health [R01-MH-50214, NIH/NCRR/OPD] FX Grant sponsor National Institute of Health; Grant numbers: R01-MH-50214, NIH/NCRR/OPD. NR 17 TC 19 Z9 21 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 SEP 5 PY 2008 VL 147B IS 6 BP 1000 EP 1002 DI 10.1002/ajmg.b.30713 PG 3 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 346EB UT WOS:000259050100047 PM 18286588 ER PT J AU Park, IH Arora, N Huo, H Maherali, N Ahfeldt, T Shimamura, A Lensch, MW Cowan, C Hochedlinger, K Daley, GQ AF Park, In-Hyun Arora, Natasha Huo, Hongguang Maherali, Nimet Ahfeldt, Tim Shimamura, Akiko Lensch, M. William Cowan, Chad Hochedlinger, Konrad Daley, George Q. TI Disease-specific induced pluripotent stem cells SO CELL LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; HUMAN SOMATIC-CELLS; DOWN-SYNDROME; DEFINED FACTORS; CRITICAL REGION; HPRT GENE; MOUSE; MUTATION; LOCUS; CHROMOSOME-21 AB Tissue culture of immortal cell strains from diseased patients is an invaluable resource for medical research but is largely limited to tumor cell lines or transformed derivatives of native tissues. Here we describe the generation of induced pluripotent stem (iPS) cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance; these diseases include adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID), Shwachman-Bodian-Diamond syndrome (SBDS), Gaucher disease (GD) type III, Duchenne (DMD) and Becker muscular dystrophy (BMD), Parkinson disease (PD), Huntington disease (HD), juvenile-onset, type 1 diabetes mellitus (JDM), Down syndrome (DS)/trisomy 21, and the carrier state of Lesch-Nyhan syndrome. Such disease-specific stem cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation and drug development. C1 [Park, In-Hyun; Arora, Natasha; Huo, Hongguang; Lensch, M. William; Daley, George Q.] Childrens Hosp, Dept Med, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Park, In-Hyun; Arora, Natasha; Huo, Hongguang; Lensch, M. William; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Park, In-Hyun; Arora, Natasha; Huo, Hongguang; Lensch, M. William; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Maherali, Nimet; Ahfeldt, Tim; Cowan, Chad; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Maherali, Nimet; Ahfeldt, Tim; Cowan, Chad; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Maherali, Nimet; Ahfeldt, Tim; Cowan, Chad; Hochedlinger, Konrad] Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. [Maherali, Nimet] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Shimamura, Akiko] Univ Washington, Div Hematol Oncol, Dept Pediat, Seattle, WA 98109 USA. [Shimamura, Akiko] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Ahfeldt, Tim] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Biol Mol Cell Biol 2, D-20246 Hamburg, Germany. [Cowan, Chad] Stowers Med Inst, Boston, MA 02115 USA. [Park, In-Hyun; Arora, Natasha; Huo, Hongguang; Maherali, Nimet; Ahfeldt, Tim; Lensch, M. William; Cowan, Chad; Hochedlinger, Konrad; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Lensch, M. William; Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Dept Med, Div Pediat Hematol Oncol, Karp Family Res Bldg 7214,300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu RI Ahfeldt, Tim/E-2935-2017 FU National Institutes of Health; Harvard Stem Cell Institute; Children's Hospital Stem Cell Program; John W. Henry Family Foundation; Burroughs Wellcome Fund; Leukemia and Lymphoma Society; Natural Sciences and Engineering Council of Canada; Sir James Lougheed Award FX G. Q. D. was supported by grants from the National Institutes of Health, the NIH Director's Pioneer Award of the NIH Roadmap for Medical Research, and private funds contributed to the Harvard Stem Cell Institute and the Children's Hospital Stem Cell Program. The work was made possible by the support and vision of Douglas and Diana Berthiaume, Jonathan and Patti Kraft, and the John W. Henry Family Foundation. G. Q. D. is a recipient of Clinical Scientist Awards in Translational Research from the Burroughs Wellcome Fund and the Leukemia and Lymphoma Society and is an Investigator of the Howard Hughes Medical Institute. K. H. was supported by the NIH Director's Innovator Award and the Harvard Stem Cell Institute. N. M. was supported by the Natural Sciences and Engineering Council of Canada and a Sir James Lougheed Award. NR 32 TC 1194 Z9 1297 U1 34 U2 406 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 5 PY 2008 VL 134 IS 5 BP 877 EP 886 DI 10.1016/j.cell.2008.07.041 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 344SL UT WOS:000258947500026 PM 18691744 ER PT J AU Walkey, CJ Spiegelman, BM AF Walkey, Christopher J. Spiegelman, Bruce M. TI A functional peroxisome proliferator-activated receptor-gamma ligand-binding domain is not required for adipogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PPAR-GAMMA; INSULIN-RESISTANCE; GENE-EXPRESSION; NUCLEAR RECEPTORS; DNA-BINDING; FAT PADS; IN-VIVO; DIFFERENTIATION; MUTATIONS; CANCER AB The nuclear hormone receptor peroxisome proliferator-activated receptor-gamma ( PPAR gamma) is the central regulator of adipogenesis. Although it is the target for several drugs that function as agonist activators, a high affinity endogenous ligand for this receptor that is involved in regulating adipogenesis has yet to be identified. Here, we investigated the requirement for ligand activation of PPAR gamma in fat cell differentiation, taking advantage of a natural mutant of this receptor that does not bind or become activated by any known natural or synthetic ligand. When ectopically expressed in PPAR gamma-null fibroblasts, this Q286P allele was able to strongly promote morphological adipogenesis, without any significant difference compared with wild-type PPAR gamma. In addition, no significant differences were found in the expression of several adipogenic genes between the wild-type and Q286P mutant alleles. To extend our studies to an in vivo setting, we performed subcutaneous injections of PPAR gamma-expressing fibroblasts into nude mice. We found that both wildtype and Q286P mutant-expressing fibroblasts were able to generate fat pads in the mice. These results suggest that the binding and activation of PPAR gamma by agonist ligands may not be required for adipogenesis under physiological conditions. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, SM958,44 Binney St, Boston, MA 02115 USA. EM Bruce_Spiegelman@dfci.harvard.edu FU National Institutes of Health [DK31405] FX This work was supported, in whole or in part, by National Institutes of Health Grant DK31405. NR 35 TC 35 Z9 35 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 2008 VL 283 IS 36 BP 24290 EP 24294 DI 10.1074/jbc.C800139200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 342YR UT WOS:000258820000002 PM 18622018 ER PT J AU Novgorodov, SA Gudz, TI Obeid, LM AF Novgorodov, Sergei A. Gudz, Tatyana I. Obeid, Lina M. TI Long-chain ceramide is a potent inhibitor of the mitochondrial permeability transition pore SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID NECROSIS-FACTOR-ALPHA; CYTOCHROME-C RELEASE; RAT-LIVER MITOCHONDRIA; APOPTOTIC CELL-DEATH; ADENINE-NUCLEOTIDE TRANSLOCASE; DEPENDENT ANION CHANNEL; 2 SEPARATE SITES; CYCLOPHILIN-D; PROTEIN PHOSPHATASE; CYCLOSPORINE-A AB The sphingolipid ceramide has been implicated in mediating cell death that is accompanied by mitochondrial functional alterations. Moreover, ceramide has been shown to accumulate in mitochondria upon induction of apoptotic processes. In this study, we sought to evaluate the effects of natural, highly hydrophobic long-chain ceramides on mitochondrial function in vitro. Ceramide in a dodecane/ethanol delivery system inhibited the opening of the mitochondrial permeability transition pore (PTP) induced by either oxidative stress, SH group cross-linking, or high Ca(2+) load, suggesting that the inhibitory point is at a level at which major PTP regulatory pathways converge. Moreover, ceramide had no effect on well known mitochondrial components that modulate PTP activity, such as cyclophilin D, voltage-dependent anion channel, adenine nucleotide transporter, and ATP synthase. The inhibitory effect of ceramide on PTP was not stereospecific, nor was there a preference for ceramide over dihydroceramide. However, the effect of ceramide on PTP was significantly influenced by the fatty acid moiety chain length. These studies are the first to show that long-chain ceramide can influence PTP at physiologically relevant concentrations, suggesting that it is the only known potent natural inhibitor of PTP. These results suggest a novel mechanism of ceramide regulation of mitochondrial function. C1 [Novgorodov, Sergei A.; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Novgorodov, Sergei A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Gudz, Tatyana I.; Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [AG16583, P20 RR 17677-04, CO6 RR018823]; Veterans Affairs Merit Awards FX This work was supported, in whole or in part, by National Institutes of Health Grant AG16583 (to L. M. O.), National Institutes of Health Grant P20 RR 17677-04 (to T. I. G.), and National Institutes of Health Grant CO6 RR018823. This work was also supported by Veterans Affairs Merit Awards (to T. I. G. and L. M. O.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 115 TC 24 Z9 25 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 2008 VL 283 IS 36 BP 24707 EP 24717 DI 10.1074/jbc.M801810200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 342YR UT WOS:000258820000040 PM 18596045 ER PT J AU Chandrasekar, B Boylston, WH Venkatachalam, K Webster, NJG Prabhu, SD Valente, AJ AF Chandrasekar, Bysani Boylston, William H. Venkatachalam, Kaliyamurthi Webster, Nicholas J. G. Prabhu, Sumanth D. Valente, Anthony J. TI Adiponectin Blocks Interleukin-18-mediated Endothelial Cell Death via APPL1-dependent AMP-activated Protein Kinase (AMPK) Activation and IKK/NF-kappa B/PTEN Suppression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN ATHEROSCLEROTIC PLAQUES; CORONARY-ARTERY-DISEASE; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; B ACTIVATION; STIMULATES ANGIOGENESIS; INSULIN-RESISTANCE; SIGNALING PATHWAY; FUNCTIONAL IL-18; HIGH-GLUCOSE AB The adipocyte-derived cytokine adiponectin is known to exert anti-inflammatory and anti-apoptotic effects. In patients with atherosclerotic cardiovascular disease, circulating levels of adiponectin correlate inversely with those of the proinflammatory, proapoptotic cytokine interleukin (IL)-18. The opposing actions of IL-18 and adiponectin on both cell survival and inflammation led us to investigate whether adiponectin signaling antagonizes IL-18-mediated endothelial cell death and to identify the underlying molecular mechanisms. Treatment with IL-18 suppressed Akt phosphorylation and its associated kinase activity, induced I kappa B kinase (IKK)-NF-kappa B-dependent PTEN activation, and promoted endothelial cell death. Pretreatment with adiponectin stimulated APPL1-dependent AMPK activation, reversed Akt inhibition in a phosphatidylinositol 3-kinase-dependent manner, blocked IKK-NF-kappa B-PTEN signaling, reduced caspase-3 activity, blocked Bax translocation, and inhibited endothelial cell death. The cytoprotective effect of adiponectin signaling was recapitulated by treatment with the pharmacological AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-riboside. Collectively, these results demonstrated that adiponectin reverses IL-18-mediated endothelial cell death through an AMPK-associated mechanism, which may thus have therapeutic potential for diminishing IL-18-dependent vascular injury and inflammation. C1 [Chandrasekar, Bysani; Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Chandrasekar, Bysani; Venkatachalam, Kaliyamurthi] S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. [Boylston, William H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Webster, Nicholas J. G.] Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA. [Prabhu, Sumanth D.] Univ Louisville, Dept Med, Inst Mol Cardiol, Louisville, KY 40292 USA. [Prabhu, Sumanth D.] Louisville Vet Affairs Med Ctr, Med Serv, Louisville, KY 40292 USA. RP Chandrasekar, B (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM chandraseka@uthscsa.edu RI Prabhu, Sumanth/D-5223-2009 FU Research Service of the Department of Veterans Affairs FX This work was supported in part by the Research Service of the Department of Veterans Affairs. NR 49 TC 76 Z9 89 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 2008 VL 283 IS 36 BP 24889 EP 24898 DI 10.1074/jbc.M804236200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 517MA UT WOS:000271617300007 PM 18632660 ER PT J AU Li, G Alt, FW Cheng, HL Brush, JW Goff, PH Murphy, MM Franco, S Zhang, Y Zha, S AF Li, Gang Alt, Frederick W. Cheng, Hwei-Ling Brush, James W. Goff, Peter H. Murphy, Mike M. Franco, Sonia Zhang, Yu Zha, Shan TI Lymphocyte-specific compensation for XLF/Cernunnos end-joining functions in V(D)J recombination SO MOLECULAR CELL LA English DT Article ID CLASS SWITCH RECOMBINATION; DNA-LIGASE-IV; DOUBLE-STRAND BREAKS; GENOMIC INSTABILITY; CHROMOSOME BREAKS; CRYSTAL-STRUCTURE; HISTONE H2AX; HUMAN XLF; MICE; TRANSLOCATIONS AB Mutations in XLF/Cernunnos (XLF) cause lymphocytopenia in humans, and various studies suggest an XLF role in classical nonhomologous end joining (C-NHEJ). We now find that XLF-deficient mouse embryonic fibroblasts are ionizing radiation (IR) sensitive and severely impaired for ability to support V(D)J recombination. Yet mature lymphocyte numbers in XLF-deficient mice are only modestly decreased. Moreover, XLF-deficient pro-B lines, while IR-sensitive, perform V(D)J recombination at nearly wild-type levels. Correspondingly, XLF/p53-double-deficient mice are not markedly prone to the pro-B lymphomas that occur in previously characterized C-NHEJ/p53-deficient mice; however, like other C-NHEJ/p53-deficient mice, they still develop medulloblastomas. Despite nearly normal V(D)J recombination in developing B cells, XLF-deficient mature B cells are moderately defective for immunoglobulin heavy-chain class switch recombination. Together, our results implicate XLF as a C-NHEJ factor but also indicate that developing mouse lymphocytes harbor cell-type-specific factors/pathways that compensate for the absence of XLF function during V(D)J recombination. C1 [Li, Gang; Alt, Frederick W.; Cheng, Hwei-Ling; Brush, James W.; Goff, Peter H.; Murphy, Mike M.; Franco, Sonia; Zhang, Yu; Zha, Shan] Harvard Univ, Sch Med, CBR Inst Biomed Res, Howard Hughes Med Inst,Childrens Hosp, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Howard Hughes Med Inst,Childrens Hosp, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU Howard Hughes Medical Institute; NCI NIH HHS [CA92625, P01 CA092625, P01 CA092625-07]; NIAID NIH HHS [P01 AI035714, P01 AI035714-07, AI35714] NR 43 TC 79 Z9 79 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD SEP 5 PY 2008 VL 31 IS 5 BP 631 EP 640 DI 10.1016/j.molcel.2008.07.017 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 347BL UT WOS:000259113800005 PM 18775323 ER PT J AU Poole, JE Johnson, GW Hellkamp, AS Anderson, J Callans, DJ Raitt, MH Reddy, RK Marchlinski, FE Yee, R Guarnieri, T Talajic, M Wilber, DJ Fishbein, DP Packer, DL Mark, DB Lee, KL Bardy, GH AF Poole, Jeanne E. Johnson, George W. Hellkamp, Anne S. Anderson, Jill Callans, David J. Raitt, Merritt H. Reddy, Ramakota K. Marchlinski, Francis E. Yee, Raymond Guarnieri, Thomas Talajic, Mario Wilber, David J. Fishbein, Daniel P. Packer, Douglas L. Mark, Daniel B. Lee, Kerry L. Bardy, Gust H. TI Prognostic importance of defibrillator shocks in patients with heart failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; PROPHYLACTIC IMPLANTATION; MYOCARDIAL DYSFUNCTION; ATRIAL-FIBRILLATION; TRIAL; TACHYARRHYTHMIA; THERAPY AB Background: Patients with heart failure who receive an implantable cardioverter-defibrillator (ICD) for primary prevention (i.e., prevention of a first life-threatening arrhythmic event) may later receive therapeutic shocks from the ICD. Information about long-term prognosis after ICD therapy in such patients is limited. Methods: Of 829 patients with heart failure who were randomly assigned to ICD therapy, we implanted the ICD in 811. ICD shocks that followed the onset of ventricular tachycardia or ventricular fibrillation were considered to be appropriate. All other ICD shocks were considered to be inappropriate. Results: Over a median follow-up period of 45.5 months, 269 patients (33.2%) received at least one ICD shock, with 128 patients receiving only appropriate shocks, 87 receiving only inappropriate shocks, and 54 receiving both types of shock. In a Cox proportional-hazards model adjusted for baseline prognostic factors, an appropriate ICD shock, as compared with no appropriate shock, was associated with a significant increase in the subsequent risk of death from all causes (hazard ratio, 5.68; 95% confidence interval [CI], 3.97 to 8.12; P<0.001). An inappropriate ICD shock, as compared with no inappropriate shock, was also associated with a significant increase in the risk of death (hazard ratio, 1.98; 95% CI, 1.29 to 3.05; P=0.002). For patients who survived longer than 24 hours after an appropriate ICD shock, the risk of death remained elevated (hazard ratio, 2.99; 95% CI, 2.04 to 4.37; P<0.001). The most common cause of death among patients who received any ICD shock was progressive heart failure. Conclusions: Among patients with heart failure in whom an ICD is implanted for primary prevention, those who receive shocks for any arrhythmia have a substantially higher risk of death than similar patients who do not receive such shocks. C1 [Poole, Jeanne E.; Fishbein, Daniel P.; Bardy, Gust H.] Univ Washington, Sch Med, Div Cardiol, Seattle, WA 98195 USA. [Johnson, George W.; Anderson, Jill; Bardy, Gust H.] Seattle Inst Cardiac Res, Seattle, WA USA. [Hellkamp, Anne S.; Mark, Daniel B.; Lee, Kerry L.] Duke Clin Res Inst, Durham, NC USA. [Callans, David J.; Marchlinski, Francis E.] Univ Penn, Philadelphia, PA 19104 USA. [Raitt, Merritt H.] Portland VA Med Ctr, Portland, OR USA. [Raitt, Merritt H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Reddy, Ramakota K.] Oregon Cardiol Assoc, Eugene, OR USA. [Yee, Raymond] Univ Western Ontario, Univ Hosp, London, ON N6A 5A5, Canada. [Guarnieri, Thomas] Johns Hopkins Univ, Baltimore, MD USA. [Talajic, Mario] Univ Montreal, Inst Cardiol Montreal, Montreal, PQ, Canada. [Wilber, David J.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Packer, Douglas L.] Mayo Clin, Rochester, MN USA. RP Poole, JE (reprint author), Univ Washington, Sch Med, Div Cardiol, 1959 NE Pacific St,Box 356422, Seattle, WA 98195 USA. EM jpoole@u.washington.edu OI Mark, Daniel/0000-0001-6340-8087; Marchlinski, Francis/0000-0001-7962-9423 FU National Heart, Lung, and Blood Institute [UO1 HL55766, UO1 HL55297, UO1 HL55496]; Medtronic; Wyeth Pharmaceuticals; Boston Scientific/Guidant; Biotronik; Biosense Webster; Siemens Acuson; Boston Scientific; St. Jude Medical FX Supported by grants from the National Heart, Lung, and Blood Institute (UO1 HL55766, UO1 HL55297, and UO1 HL55496) and by Medtronic and Wyeth Pharmaceuticals. Dr. Poole reports receiving lecture fees from Medtronic and Boston Scientific/Guidant, grant support from Biotronik, and consulting fees from Philips; Ms. Anderson, receiving lecture fees from Boston Scientific/Guidant; Dr. Callans, receiving lecture fees from Biosense Webster, Siemens Acuson, Boston Scientific, and Medtronic and consulting fees from St. Jude Medical; Dr. Reddy, receiving consulting fees and lecture fees from Boston Scientific/Guidant, Medtronic, and St. Jude and holding stock options in Cambridge Heart; Dr. Marchlinski, receiving consulting fees, lecture fees, and grant support from Biosense Webster, lecture fees and grant support from Boston Scientific and St. Jude Medical, lecture fees from Medtronic, and consulting fees from GE Healthcare; Dr. Yee, receiving consulting fees from Medtronic; Dr. Talajic, receiving consulting fees and lecture fees from Medtronic and lecture fees from St. Jude Medical; Dr. Wilber, receiving consulting fees and lecture fees from Medtronic and lecture fees from Boston Scientific and St. Jude Medical; Dr. Fishbein, receiving lecture fees from Medtronic; Dr. Packer, receiving consulting fees from Medtronic and Boston Scientific/ Guidant, royalties from St. Jude Medical, and grant support from Boston Scientific; Dr. Mark, receiving consulting fees, lecture fees, and research grants from Medtronic and fees as editor of the American Heart Journal from Mosby; Dr. Lee, receiving grant support and consulting fees from Medtronic; and Dr. Bardy, receiving grant support from and having intellectual property rights with Medtronic, receiving consulting fees and grant support from Philips, receiving grant support from Laerdal and being a founder of and board member of and having equity and intellectual property rights with Cameron Health. No other potential conflict of interest relevant to this article was reported. We thank R. Conklin for help in the preparation of the manuscript. NR 21 TC 572 Z9 582 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 4 PY 2008 VL 359 IS 10 BP 1009 EP 1017 DI 10.1056/NEJMoa071098 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 343KN UT WOS:000258852500005 PM 18768944 ER PT J AU Hornig, M Briese, T Buie, T Bauman, ML Lauwers, G Siemetzki, U Hummel, K Rota, PA Bellini, WJ O'Leary, JJ Sheils, O Alden, E Pickering, L Lipkin, WI AF Hornig, Mady Briese, Thomas Buie, Timothy Bauman, Margaret L. Lauwers, Gregory Siemetzki, Ulrike Hummel, Kimberly Rota, Paul A. Bellini, William J. O'Leary, John J. Sheils, Orla Alden, Errol Pickering, Larry Lipkin, W. Ian TI Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study SO PLOS ONE LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; MUMPS-RUBELLA VACCINATION; LYMPHOCYTE CYTOKINE PROFILES; INFLAMMATORY-BOWEL-DISEASE; SPECTRUM DISORDER; NO EVIDENCE; GASTROINTESTINAL SYMPTOMS; NODULAR HYPERPLASIA; CAUSAL ASSOCIATION; REGRESSIVE AUTISM AB Background: The presence of measles virus (MV) RNA in bowel tissue from children with autism spectrum disorders (ASD) and gastrointestinal (GI) disturbances was reported in 1998. Subsequent investigations found no associations between MV exposure and ASD but did not test for the presence of MV RNA in bowel or focus on children with ASD and GI disturbances. Failure to replicate the original study design may contribute to continued public concern with respect to the safety of the measles, mumps, and rubella (MMR) vaccine. Methodology/Principal Findings: The objective of this case-control study was to determine whether children with GI disturbances and autism are more likely than children with GI disturbances alone to have MV RNA and/or inflammation in bowel tissues and if autism and/or GI episode onset relate temporally to receipt of MMR. The sample was an age-matched group of US children undergoing clinically-indicated ileocolonoscopy. Ileal and cecal tissues from 25 children with autism and GI disturbances and 13 children with GI disturbances alone (controls) were evaluated by real-time reverse transcription (RT)-PCR for presence of MV RNA in three laboratories blinded to diagnosis, including one wherein the original findings suggesting a link between MV and ASD were reported. The temporal order of onset of GI episodes and autism relative to timing of MMR administration was examined. We found no differences between case and control groups in the presence of MV RNA in ileum and cecum. Results were consistent across the three laboratory sites. GI symptom and autism onset were unrelated to MMR timing. Eighty-eight percent of ASD cases had behavioral regression. Conclusions/Significance: This study provides strong evidence against association of autism with persistent MV RNA in the GI tract or MMR exposure. Autism with GI disturbances is associated with elevated rates of regression in language or other skills and may represent an endophenotype distinct from other ASD. C1 [Hornig, Mady; Briese, Thomas; Siemetzki, Ulrike; Lipkin, W. Ian] Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY 10027 USA. [Buie, Timothy] Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Boston, MA USA. [Bauman, Margaret L.] Massachusetts Gen Hosp, Dept Neurol, Dept Pediat, LADDERS, Boston, MA USA. [Lauwers, Gregory] Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA USA. [Hummel, Kimberly; Rota, Paul A.; Bellini, William J.] Ctr Dis Control & Prevent, Measles Mumps Rubella & Herpesvirus Lab Branch, Atlanta, GA USA. [O'Leary, John J.; Sheils, Orla] Trinity Coll Dublin, Dept Histopathol, Dublin, Ireland. [Alden, Errol] American Acad Pediat, Elk Grove Village, IL USA. [Pickering, Larry] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. RP Hornig, M (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY 10027 USA. EM mady.hornig@columbia.edu; wil2001@columbia.edu RI Sheils, Orla Sheils/B-8461-2015 OI Sheils, Orla Sheils/0000-0002-4493-9496 FU CDC [U50 CCU522351]; National Institutes of Health [AI57158, HL083850, NS47537] FX This work was supported by CDC grant U50 CCU522351 to AAP and by National Institutes of Health awards AI57158 (Northeast Biodefense Center-Lipkin), HL083850, and NS47537. Role of Study Sponsors: Members of the funding organization (AAP) and its sponsor (CDC) participated along with experts in virology and neurovirology, autism pathogenesis, and vaccine design and safety; representatives of the autism advocacy community; and study collaborators in an Oversight Committee that reviewed and agreed to all aspects of study design prior to data collection. The final decision to submit for publication was the responsibility of all study collaborators. NR 49 TC 50 Z9 52 U1 4 U2 39 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 SEP 4 PY 2008 VL 3 IS 9 AR e3140 DI 10.1371/journal.pone.0003140 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 422HU UT WOS:000264419100008 PM 18769550 ER PT J AU Shaywitz, AJ Courtney, KD Patnaik, A Cantley, LC AF Shaywitz, Adam J. Courtney, Kevin D. Patnaik, Akash Cantley, Lewis C. TI PI3K enters beta-testing SO CELL METABOLISM LA English DT Editorial Material ID PHOSPHOINOSITIDE 3-KINASE; CATALYTIC SUBUNIT; P110-BETA; P110-GAMMA; METABOLISM; DELETION; GROWTH; MICE AB Phosphoinositide-3-OH kinases (PI3K) are critical regulators of cell metabolism, growth, and survival. In a recent publication in Nature, Jia et al. (2008) identify specific functions of the p110 beta isoform of PI3K in glucose metabolism, cellular proliferation, and tumorigenesis. C1 [Shaywitz, Adam J.; Courtney, Kevin D.; Patnaik, Akash; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. [Shaywitz, Adam J.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. [Courtney, Kevin D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Patnaik, Akash] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM041890] NR 12 TC 5 Z9 6 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD SEP 3 PY 2008 VL 8 IS 3 BP 179 EP 181 DI 10.1016/j.cmet.2008.08.011 PG 3 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 344PJ UT WOS:000258939500004 PM 18762017 ER PT J AU Doria, A Patti, ME Kahn, CR AF Doria, Alessandro Patti, Mary-Elizabeth Kahn, C. Ronald TI The emerging genetic architecture of type 2 diabetes SO CELL METABOLISM LA English DT Review ID GENOME-WIDE ASSOCIATION; NUTRITION EXAMINATION SURVEY; HUMAN SKELETAL-MUSCLE; AMYLOID BETA-PROTEIN; BODY-MASS INDEX; INSULIN-RESISTANCE; COMMON VARIANTS; GLUCOSE-HOMEOSTASIS; MEXICAN-AMERICANS; TRANSCRIPTION-FACTOR-7-LIKE-2 TCF7L2 AB Type 2 diabetes is a genetically heterogeneous disease, with several relatively rare monogenic forms and a number of more common forms resulting from a complex interaction of genetic and environmental factors. Previous studies using a candidate gene approach, family linkage studies, and gene expression profiling uncovered a number of type 2 genes, but the genetic basis of common type 2 diabetes remained unknown. Recently, a new window has opened on defining potential type 2 diabetes genes through genome-wide SNP association studies of very large populations of individuals with diabetes. This review explores the pathway leading to discovery of these genetic effects, the impact of these genetic loci on diabetes risk, the potential mechanisms of action of the genes to alter glucose homeostasis, and the limitations of these studies in defining the role of genetics in this important disease. C1 [Doria, Alessandro; Patti, Mary-Elizabeth; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIH [DK60837, DK55523, DK62948]; Graetz Foundation; Research Grant from the American Diabetes Association FX Part of the research discussed in this paper was supported by NIH grants DK60837 (Diabetes Genome Anatomy Project), DK55523, and DK62948, the Graetz Foundation and a Research Grant from the American Diabetes Association (to M.E.P.). NR 119 TC 152 Z9 159 U1 3 U2 23 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 SEP 3 PY 2008 VL 8 IS 3 BP 186 EP 200 DI 10.1016/j.cmet.2008.08.006 PG 15 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 344PJ UT WOS:000258939500007 PM 18762020 ER PT J AU Song, JW Misgeld, T Kang, H Knecht, S Lu, J Cao, Y Cotman, SL Bishop, DL Lichtman, JW AF Song, Jae W. Misgeld, Thomas Kang, Hyuno Knecht, Sharm Lu, Ju Cao, Yi Cotman, Susan L. Bishop, Derron L. Lichtman, Jeff W. TI Lysosomal activity associated with developmental axon pruning SO JOURNAL OF NEUROSCIENCE LA English DT Article DE synapse elimination; lysosome; autophagy; degradation; axon pruning; retraction bulb ID CLIMBING FIBER INNERVATION; SYNAPSE ELIMINATION; NERVOUS-SYSTEM; PURKINJE-CELLS; FLUORESCENT PROTEINS; MOUSE MODEL; AUTOPHAGY; MICE; RAT; DEGENERATION AB Clearance of cellular debris is a critical feature of the developing nervous system, as evidenced by the severe neurological consequences of lysosomal storage diseases in children. An important developmental process, which generates considerable cellular debris, is synapse elimination, in which many axonal branches are pruned. The fate of these pruned branches is not known. Here, we investigate the role of lysosomal activity in neurons and glia in the removal of axon branches during early postnatal life. Using a probe for lysosomal activity, we observed robust staining associated with retreating motor axons. Lysosomal function was involved in axon removal because retreating axons were cleared more slowly in a mouse model of a lysosomal storage disease. In addition, we found lysosomal activity in the cerebellum at the time of, and at sites where, climbing fibers are eliminated. We propose that lysosomal activity is a central feature of synapse elimination. Moreover, staining for lysosomal activity may serve as a marker for regions of the developing nervous system undergoing axon pruning. C1 [Song, Jae W.; Kang, Hyuno; Lu, Ju; Lichtman, Jeff W.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Misgeld, Thomas] Tech Univ Munich, Inst Neurosci, D-80802 Munich, Germany. [Knecht, Sharm; Bishop, Derron L.] Indiana Univ, Sch Med, Dept Med Educ, Muncie, IN 47306 USA. [Cao, Yi; Cotman, Susan L.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. [Cao, Yi; Cotman, Susan L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Lichtman, JW (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 52 Oxford St, Cambridge, MA 02138 USA. EM jeff@mcb.harvard.edu FU National Institutes of Health [R01NS020364-25, 1R15NS048055]; Alpha Omega Alpha Carolyn L. Kuckein Medical Student Fellowship; Alexander von Humboldt Foundation; Institute of Advanced Study-Technical University Munich; Deutsche Forschungsgemeinschaft; Center of Integrated Protein Science Munich; Batten Disease Support and Research Association FX This work was supported by the National Institutes of Health Grants R01NS020364-25 (J.W.L.) and 1R15NS048055 ( D. L. B.). J.W.S. received support from the Alpha Omega Alpha Carolyn L. Kuckein Medical Student Fellowship. T. M. acknowledges support from the Alexander von Humboldt Foundation, the Institute of Advanced Study-Technical University Munich, the Deutsche Forschungsgemeinschaft, and the Center of Integrated Protein Science Munich. Y.C. received support from Batten Disease Support and Research Association. We thank N. Mizushima and RIKEN for GFP-LC3 mice, members of the W. Regehr lab for cerebellar acute section techniques, and Sara Haddad, Kate Mahoney, and Edith Robbins for mouse facility care. We acknowledge constructive suggestions and help from our laboratory colleagues. NR 41 TC 44 Z9 44 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 3 PY 2008 VL 28 IS 36 BP 8993 EP 9001 DI 10.1523/JNEUROSCI.0720-08.2008 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 343XY UT WOS:000258890900016 PM 18768693 ER PT J AU Heidemann, C Sun, Q van Dam, RM Meigs, JB Zhang, CL Tworoger, SS Mantzoros, CS Hu, FB AF Heidemann, Christin Sun, Qi van Dam, Rob M. Meigs, James B. Zhang, Cuilin Tworoger, Shelley S. Mantzoros, Christos S. Hu, Frank B. TI Total and high-molecular-weight adiponectin and resistin in relation to the risk for type 2 diabetes in women SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE; METABOLIC SYNDROME; SERUM RESISTIN; PLASMA RESISTIN; ADIPOSE-TISSUE; OLDER MEN; MELLITUS; OBESITY; HUMANS AB Background: Adiponectin and resistin are recently discovered adipokines that may provide a molecular link between adiposity and type 2 diabetes. Objective: To evaluate whether total and high-molecular-weight adiponectin and resistin are associated with future risk for type 2 diabetes, independent of obesity and other known diabetes risk factors. Design: Prospective, nested, case - control study. Setting: United States. Participants: 1038 initially healthy women of the Nurses' Health Study who developed type 2 diabetes after blood sampling (1989 to 1990) through 2002 and 1136 matched control participants. Measurements: Plasma concentrations of total and high-molecular-weight adiponectin and resistin. Results: In multivariate models including body mass index, higher total and high-molecular-weight adiponectin levels were associated with a substantially lower risk for type 2 diabetes (odds ratio [OR] comparing the highest with the lowest quintiles, 0.17 [95% CI, 0.12 to 0.25] for total adiponectin and 0.10 [CI, 0.06 to 0.15] for high-molecular-weight adiponectin). A higher ratio of high-molecular-weight to total adiponectin was associated with a statistically significantly lower risk even after adjustment for total adiponectin (OR, 0.45 [CI, 0.31 to 0.65]). In the multivariate model without body mass index, higher resistin levels were associated with a higher risk for diabetes (OR, 1.68 [CI, 1.25 to 2.25]), but the association was no longer statistically significant after adjustment for body mass index (OR, 1.28 [CI, 0.93 to 1.76]). Limitation: The findings apply mainly to white women and could be partly explained by residual confounding from imperfectly measured or unmeasured variables. Conclusion: Adiponectin is strongly and inversely associated with risk for diabetes, independent of body mass index, whereas resistin is not. The ratio of high-molecular-weight to total adiponectin is related to risk for diabetes independent of total adiponectin, suggesting an important role of the relative proportion of high-molecular-weight adiponectin in diabetes pathogenesis. C1 Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NIH, Bethesda, MD 20892 USA. RP Hu, FB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02215 USA. EM frank.hu@channing.harvard.edu RI van Dam, Rob/F-9674-2010; OI van Dam, Rob/0000-0002-7354-8734; Tworoger, Shelley/0000-0002-6986-7046 FU National Institute of Child Health & Human Development [CA87969, DK58845, DK58785]; German Academic Exchange Service; Hans & Eugenia Juetting Foundation; American Diabetes; Tanita Corporation; Beth Israel Deaconess Medical Center FX By the National Institutes of Health and the Intramural Research Program of the National Institute of Child Health & Human Development (grants CA87969, DK58845 and DK58785). Dr. Heidemann was supported by fellowships of the German Academic Exchange Service and the Hans & Eugenia Juetting Foundation. Dr. Meigs received a Career Development Award from the American Diabetes. Dr. Mantzoros was supported by discretionary grants from the Tanita Corporation and Beth Israel Deaconess Medical Center. NR 48 TC 121 Z9 126 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 2 PY 2008 VL 149 IS 5 BP 307 EP W66 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 348SD UT WOS:000259229300003 PM 18765700 ER PT J AU Groenveld, HF Januzzi, JL Damman, K van Wijngaarden, J Hillege, HL van Veldhuisen, DJ van der Meer, P AF Groenveld, Hessel F. Januzzi, James L. Damman, Kevin van Wijngaarden, Jan Hillege, Hans L. van Veldhuisen, Dirk J. van der Meer, Peter TI Anemia and mortality in heart failure patients - A systematic review and meta-analysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE heart failure; anemia; prognosis ID BRAIN NATRIURETIC PEPTIDE; CHRONIC KIDNEY-DISEASE; PRESERVED SYSTOLIC FUNCTION; NEW-ONSET; RENAL-INSUFFICIENCY; DARBEPOETIN-ALPHA; HEMOGLOBIN LEVEL; INTRAVENOUS IRON; PROGNOSTIC-SIGNIFICANCE; EJECTION FRACTION AB Objectives The aim of this study was to assess the effect of anemia on mortality in chronic heart failure (CHF). Background Anemia is frequently observed in patients with CHF, and evidence suggests that anemia might be associated with an increased mortality. Methods A systematic literature search in MEDLINE ( through November 2007) for English language articles was performed. In addition, a manual search was performed. We included cohort studies and retrospective secondary analyses of randomized controlled trials whose primary objective was to analyze the association between anemia and mortality in CHF. Of a total of 1,327 initial studies, we included 34 studies, comprising 153,180 patients. Information on study design, patient characteristics, outcome, and potential confounders were extracted. Results Anemia was defined by criteria used in the original articles. Of the 153,180 CHF patients, 37.2% were anemic. After a minimal follow-up of 6 months, 46.8% of anemic patients died compared with 29.5% of nonanemic patients. Crude mortality risk of anemia was odds ratio 1.96 (95% confidence interval: 1.74 to 2.21, p < 0.001). Lower baseline hemoglobin values were associated with increased crude mortality rates (r = -0.396, p = 0.025). Adjusted hazard ratios showed an increased adjusted risk for anemia (hazard ratio 1.46 [95% confidence interval: 1.26 to 1.69, p < 0.001]). Subgroup analysis showed no significant difference between mortality risk of anemia in diastolic or systolic CHF. Conclusions Anemia is associated with an increased risk of mortality in both systolic and diastolic CHF. Anemia should, therefore, be considered as a useful prognosticator, and therapeutic strategies aimed to increase hemoglobin levels in CHF should be investigated. C1 [Januzzi, James L.; van der Meer, Peter] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med,Cardiovasc Res Ctr, Boston, MA 02114 USA. [Groenveld, Hessel F.; Damman, Kevin; Hillege, Hans L.; van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands. [van Wijngaarden, Jan] Deventer Hosp, Dept Cardiol, Deventer, Netherlands. RP van der Meer, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med,Cardiovasc Res Ctr, Charles River Plaza,185 Cambridge St, Boston, MA 02114 USA. EM pvandermeer@partners.org RI van Veldhuisen, Dirk Jan/E-8967-2014 FU Netherlands Heart Foundation [2006B157, D97-017]; Dutch Scientific Organization [825-07-011] FX Dr. Damman is supported by the Netherlands Heart Foundation (grant 2006B157). Dr. van Veldhuisen is a Clinical Established Investigator of the Netherlands Heart Foundation (D97-017). Dr. van der Meer is supported by the Dutch Scientific Organization (Rubicon grant: 825-07-011). NR 60 TC 275 Z9 287 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 2 PY 2008 VL 52 IS 10 BP 818 EP 827 DI 10.1016/j.jacc.2008.04.061 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 341NC UT WOS:000258720200004 PM 18755344 ER PT J AU Orasanu, G Ziouzenkova, O Devchand, PR Nehra, V Hamdy, O Horton, ES Plutzky, J AF Orasanu, Gabriela Ziouzenkova, Ouliana Devchand, Pallavi R. Nehra, Vedika Hamdy, Osama Horton, Edward S. Plutzky, Jorge TI The peroxisome proliferator-activated receptor-gamma agonist pioglitazone represses inflammation in a peroxisome proliferator-activated receptor-alpha- dependent manner in vitro and in vivo in mice SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE inflammation; VCAM-1; PPAR ID TYPE-2 DIABETES-MELLITUS; RANDOMIZED CONTROLLED-TRIAL; CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE SYNDROME; CELL-ADHESION MOLECULES; HUMAN ENDOTHELIAL-CELLS; INTIMA-MEDIA THICKNESS; PPAR-ALPHA; KAPPA-B; CARDIOVASCULAR EVENTS AB Objectives Our aim was to investigate if the peroxisome proliferator-activated receptor (PPAR)-gamma agonist pioglitazone modulates inflammation through PPAR alpha mechanisms. Background The thiazolidinediones (TZDs) pioglitazone and rosiglitazone are insulin-sensitizing PPAR gamma agonists used to treat type 2 diabetes (T2DM). Despite evidence for TZDs limiting inflammation and atherosclerosis, questions exist regarding differential responses to TZDs. In a double-blinded, placebo-controlled 16-week trial among recently diagnosed T2DM subjects (n = 34), pioglitazone-treated subjects manifested lower triglycerides and lacked the increase in soluble vascular cell adhesion molecules (sVCAM)-1 evident in the placebo group. Previously we reported PPAR alpha but not PPAR alpha agonists could repress VCAM-1 expression. Since both triglyceride-lowering and VCAM-1 repression characterize PPAR alpha activation, we studied pioglitazone's effects via PPAR alpha. Methods Pioglitazone effects on known PPAR alpha responses-ligand binding domain activation and PPAR alpha target gene expression -were tested in vitro and in vivo, including in wild-type and PPAR alpha-deficient cells and mice, and compared with the effects of other PPAR alpha (rosiglitazone) and PPAR alpha (WY14643) agonists. Results Pioglitazone repressed endothelial TNF alpha-induced VCAM-1 messenger ribonucleic acid expression and promoter activity, and induced hepatic I kappa B alpha in a manner dependent on both pioglitazone exposure and PPAR alpha expression. Pioglitazone also activated the PPAR alpha ligand binding domain and induced PPAR alpha target gene expression, with in vitro effects that were most pronounced in endothelial cells. In vivo, pioglitazone administration modulated sVCAM-1 levels and I kappa B alpha expression in wild-type but not PPAR alpha-deficient mice. Conclusions Pioglitazone regulates inflammatory target genes in hepatic (I kappa B alpha) and endothelial (VCAM-1) settings in a PPAR alpha-dependent manner. These data offer novel mechanisms that may underlie distinct TZD responses. C1 [Orasanu, Gabriela; Ziouzenkova, Ouliana; Devchand, Pallavi R.; Nehra, Vedika; Plutzky, Jorge] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Hamdy, Osama; Horton, Edward S.] Joslin Diabet Ctr, Clin Res Ctr, Boston, MA 02215 USA. [Orasanu, Gabriela; Ziouzenkova, Ouliana; Devchand, Pallavi R.; Nehra, Vedika; Hamdy, Osama; Horton, Edward S.; Plutzky, Jorge] Harvard Univ, Sch Med, Boston, MA USA. RP Plutzky, J (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 77 Ave Louis Pasteur,NRB 742, Boston, MA 02115 USA. EM jplutzky@rics.bwh.harvard.edu RI Ziouzenkova, Ouliana/B-3690-2012 FU National Institutes of Health [R01 HL071745]; Takeda Pharmaceuticals; GlaxoSmithKline FX Dr. Plutzky has received grant support from the National Institutes of Health (R01 HL071745). The clinical trial presented here was supported by Takeda Pharmaceuticals (Dr. Horton, primary investigator). The investigators have received prior funding from GlaxoSmithKline and Takeda Pharmaceuticals, although not specifically for the support of the pre-clinical murine studies included here. NR 91 TC 59 Z9 64 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 2 PY 2008 VL 52 IS 10 BP 869 EP 881 DI 10.1016/j.jacc.2008.04.055 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 341NC UT WOS:000258720200013 PM 18755353 ER PT J AU Gavanescu, I Benoist, C Mathis, D AF Gavanescu, Irina Benoist, Christophe Mathis, Diane TI B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; B lymphocytes; tolerance; autoantibody ID ANTIGEN-PRESENTING CELLS; NONOBESE DIABETIC MICE; T-CELLS; NEGATIVE SELECTION; AUTOIMMUNE-DISEASE; THYMIC EXPRESSION; LYMPH-NODES; IN-VIVO; AUTOANTIBODIES; LYMPHOCYTES AB Autoimmune regulator (Aire)-deficient mice and humans have circulating autoantibodies against a multitude of organs and multiorgan autoinflammatory infiltrates. It is not known to what extent autoantibodies or their source, B lymphocytes, are required for disease onset or progression. We show in this research that B cells must be present for Aire-deficient mice to develop fulminant infiltrates. We found no evidence that autoantibodies were directly pathogenic; rather, B cells appeared to play a critical early role in T cell priming or expansion. A therapeutic reagent directed against 8 cells, Rituximab, induced remission of the autoimmune disease in Aire-deficient mice, raising the hope of applying it to human patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). C1 [Gavanescu, Irina; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU National Institutes of Health [R01 DK60027, T32 CA09382, F32 AI62010]; Young Chair funds; Joslin's Diabetes and Endocrinology Research Center [P30 DK36836] FX We thank Dr. Wenyu Jiang for scoring of samples, Joyce LaVecchia and Girijesh Buruzula for flow cytometry, and Vanessa Tran for mouse rearing. This work was supported by the National Institutes of Health Grant R01 DK60027 and Young Chair funds to D.M. and C.B. and by Joslin's Diabetes and Endocrinology Research Center cores(P30 DK36836). I.G. received fellowships from the National Institutes of Health (T32 CA09382 and F32 AI62010). NR 42 TC 37 Z9 37 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 SEP 2 PY 2008 VL 105 IS 35 BP 13009 EP 13014 DI 10.1073/pnas.0806874105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 350HJ UT WOS:000259343000070 PM 18755889 ER PT J AU Tresoldi, S Kim, YH Blake, MA Harisinghani, MG Hahn, PF Baker, SP Mueller, PR Kandarpa, K AF Tresoldi, Silvia Kim, Young H. Blake, Michael A. Harisinghani, Mukesh G. Hahn, Peter F. Baker, Stephen P. Mueller, Peter R. Kandarpa, Krishna TI Adult intestinal intussusception: can abdominal MDCT distinguish an intussusception caused by a lead point? SO ABDOMINAL IMAGING LA English DT Article DE computed tomography; spiral-computed tomography; multislice abdominal imaging; small bowel disease; large bowel disease ID SMALL-BOWEL INTUSSUSCEPTION; COMPUTED-TOMOGRAPHY; CT FINDINGS; CELIAC-DISEASE; DIAGNOSIS; APPEARANCE; MANAGEMENT; FEATURES AB Background: Aim of our study was to assess the ability of computed tomography to distinguish between an intussusception with a lead-point from one without it. Methods: Approval was granted by the Institutional Review Board. Ninety-three consecutive patients diagnosed with an intussusception on abdominal CT were classified with or without lead-point by surgery, clinical or radiological follow-up. Two radiologists blinded to the classification independently reviewed the CT images for predefined predictive variables. Results: Non-lead-point intussusception was shorter in length (mean 4.9 vs. 11.1 cm for Reader 1 (R1); mean 4.0 vs. 8.9 cm for Reader 2 (R2), respectively, P < 0.001), smaller in axial diameter (mean 3.0 vs. 4.8 cm for R1; mean 2.8 vs. 4.4 cm for R2, P < 0.001, respectively), less likely associated with obstruction (P = 0.002 R1; P = 0.039 R2) and infiltration (P < 0.001 for R1, P = 0.003 R2) than lead-point intussusception. Conclusions: Abdominal CT is helpful in distinguishing between an intussusception with a lead-point from one without a lead-point. Length, axial diameter, and their product, as well as obstruction and infiltration, all suggest the presence of a lead-point. Analysis of CT findings can reduce unnecessary imaging follow-up or operation. C1 [Kim, Young H.; Kandarpa, Krishna] Univ Massachusetts, Sch Med, Umass Mem Med Ctr, Dept Radiol, Worcester, MA 01655 USA. [Tresoldi, Silvia] Univ Milan, San Paolo Hosp, Dept Diagnost & Intervent Radiol, I-20142 Milan, Italy. [Blake, Michael A.; Harisinghani, Mukesh G.; Hahn, Peter F.; Mueller, Peter R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Baker, Stephen P.] Univ Massachusetts, Sch Med, IS Bioinformat Unit, Worcester, MA 01655 USA. RP Kim, YH (reprint author), Univ Massachusetts, Sch Med, Umass Mem Med Ctr, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM kimy@ummhc.org NR 34 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD SEP PY 2008 VL 33 IS 5 BP 582 EP 588 DI 10.1007/s00261-007-9328-8 PG 7 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 338WN UT WOS:000258540200013 PM 17924160 ER PT J AU Kutner, L Olson, CK Schlozman, S Goldstein, M Warner, D Beresin, EV AF Kutner, Lawrence Olson, Cheryl K. Schlozman, Steven Goldstein, Mark Warner, Dorothy Beresin, Eugene V. TI Training Pediatric Residents and Pediatricians About Adolescent Mental Health Problems: A Proof-of-Concept Pilot for a Proposed National Curriculum SO ACADEMIC PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CARE CLINICIAN USE; PSYCHOSOCIAL PROBLEMS; UNMET NEED; DISORDERS; CHILDREN; DEPRESSION; COMORBIDITY; PREVALENCE; MANAGEMENT AB Objective: This article presents a DVD-based educational program intended to help pediatric residents and practicing pediatricians recognize and respond to adolescent depression in busy primary care settings. Methods: Representatives from pediatrics and adolescent medicine, child and adolescent psychiatry and psychology, and experts in the creation of educational mental health programs met to design a multimedia approach to improving the mental health diagnostic skills among pediatric residents, The authors chose depression as the initial topic because of its relatively high prevalence among children and adolescents, and evidence suggesting that pediatricians may have difficulty diagnosing this disorder in the primary cart, setting. The authors created a 30-minute DVD program featuring depressed adolescents and experts in child-psychiatry and adolescent medicine. After viewing the DVD, residents in the training program, as well as practicing pediatricians, completed a standardized survey to assess the usefulness and attractiveness of this approach to pediatric education. Results: The survey results support the potential value of this type of material and the feasibility of similar programs in addressing an array of mental health concerns in pediatric residencies. Participants found the program useful and indicated interest in receiving more educational programs in this format. Conclusion: The authors suggest that the relative ease with which initiatives such as this media-based approach call be implemented make this educational technique appropriate and feasible on a large scale for programs throughout the nation and for a variety of mental health concerns. Academic Psychiatry 2008; 32:429-437 C1 [Kutner, Lawrence; Olson, Cheryl K.; Schlozman, Steven; Goldstein, Mark; Warner, Dorothy; Beresin, Eugene V.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Beresin, EV (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Wang 812,Parkman St, Boston, MA 02114 USA. EM cberesin@partners.org NR 39 TC 7 Z9 7 U1 1 U2 4 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 SEP-OCT PY 2008 VL 32 IS 5 BP 429 EP 437 DI 10.1176/appi.ap.32.5.429 PG 9 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 362MQ UT WOS:000260202200014 PM 18945983 ER PT J AU Cody, V Pace, J Rosowsky, A AF Cody, Vivian Pace, Jim Rosowsky, Andre TI Structural analysis of a holoenzyme complex of mouse dihydrofolate reductase with NADPH and a ternary complex with the potent and selective inhibitor 2,4-diamino-6-(2 '-hydroxydibenz[b,f]-azepin-5-yl)methylpteridine SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID PNEUMOCYSTIS-CARINII; MACROMOLECULAR CRYSTALLOGRAPHY; CRYSTAL-STRUCTURES; SIDE-CHAIN; DESIGN; METHOTREXATE; RESISTANCE; INSIGHTS; ANALOGS; SYSTEM AB It has been shown that 2,4-diamino-6-arylmethylpteridines and 2,4-diamino-5-arylmethylpyrimidines containing an O-carboxylalkyloxy group in the aryl moiety are potent and selective inhibitors of the dihydrofolate reductase (DHFR) from opportunistic pathogens such as Pneumocystis carinii, the causative agent of Pneumocystis pneumonia in HIV/AIDS patients. In order to understand the structure-activity profile observed for a series of substituted dibenz[b,f]azepine antifolates, the crystal structures of mouse DHFR (mDHFR; a mammalian homologue) holo and ternary complexes with NADPH and the inhibitor 2,4-diamino-6-(2'-hydroxydibenz[b,f]azepin-5-yl)methylpteridine were determined to 1.9 and 1.4 angstrom resolution, respectively. Structural data for the ternary complex with the potent O-(3-carboxypropyl) inhibitor PT684 revealed no electron density for the O-carboxylalkyloxy side chain. The side chain was either cleaved or completely disordered. The electron density fitted the less potent hydroxyl compound PT684a. Additionally, cocrystallization of mDHFR with NADPH and the less potent 2'-(4-carboxybenzyl) inhibitor PT682 showed no electron density for the inhibitor and resulted in the first report of a holoenzyme complex despite several attempts at crystallization of a ternary complex. Modeling data of PT682 in the active site of mDHFR and P. carinii DHFR (pcDHFR) indicate that binding would require ligand-induced conformational changes to the enzyme for the inhibitor to fit into the active site or that the inhibitor side chain would have to adopt an alternative binding mode to that observed for other carboxyalkyloxy inhibitors. These data also show that the mDHFR complexes have a decreased active-site volume as reflected in the relative shift of helix C (residues 59-64) by 0.6 angstrom compared with pcDHFR ternary complexes. These data are consistent with the greater inhibitory potency against pcDHFR. C1 [Cody, Vivian; Pace, Jim] Hauptman Woodward Med Res Inst, Dept Biol Struct, Buffalo, NY 14203 USA. [Cody, Vivian] SUNY Buffalo, Buffalo, NY 14260 USA. [Rosowsky, Andre] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cody, V (reprint author), Hauptman Woodward Med Res Inst, Dept Biol Struct, 700 Ellicott St, Buffalo, NY 14203 USA. EM cody@hwi.buffalo.edu FU NIGMS NIH HHS [GM51670, R01 GM051670, R01 GM051670-13] NR 26 TC 7 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD SEP PY 2008 VL 64 BP 977 EP 984 DI 10.1107/S0907444908022348 PN 9 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 337BZ UT WOS:000258411800010 PM 18703847 ER PT J AU Yuan, Q Wilbur, DC AF Yuan, Qin Wilbur, David C. TI Original cervical cytology and follow-up biopsy results in positive high risk human papillomavirus DNA tests with high-level results SO ACTA CYTOLOGICA LA English DT Article DE cervical cancer; human papillomavirus; screening ID HYBRID CAPTURE-II; E2 GENE DISRUPTION; VIRAL LOAD; INTRAEPITHELIAL NEOPLASIA; MESSENGER-RNA; WOMEN; GRADE; HPV; TYPE-16; LESIONS AB Objective To ascertain Pap test and biopsy results of specimens with high levels of human papillomavirus (HPV) DNA and compare atypical squamous cells of undetermined significance (ASC-US) populations with HPV DNA. Study Design Positive HPV tests with relative light unit (RLU) values >= 1,000 were identified and original Pap test and follow-up biopsy results recorded. Pap test and biopsy results for ASC-US were compared to positive results with RLU < 1,000. Results From 1,892 total HPV-positive tests, 156 specimens with high RLU were identified; 145 had biopsies. The interpretations of the corresponding Pap tests were as follows: negative for intraepithelial lesion and malignancy, 3; ASC-US, 87; ASC, cannot exclude high grade squamous intraepithelial lesion, 5; low grade squamous intraepithelial lesion, 40 and high grade squamous intraepithelial lesion, 10. Biopsies showed 60 negative, 58 cervical intraepithelial neoplasia (CIN) 1 and 27 CIN 2+. In the highly positive ASC-US group, biopsy showed higher percentage of CIN 1 (33% vs. 16%) compared to the low-positive group. Conclusion Compared to low-positive results, high-positive results showed more abnormal Pap tests. CIN 1 was a more likely result for big-positve ASC-US. More transient infections may account for these findings. The results do not argue for different management schemes between the categories. C1 [Yuan, Qin; Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yuan, Qin] Ruijin Hosp, Clin Lab & Diagnost Ctr, Shanghai, Peoples R China. [Yuan, Qin] Shanghai Jiao Tong Univ, Shanghai 200030, Peoples R China. [Wilbur, David C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Wilbur, DC (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 120, Boston, MA 02114 USA. EM dwilbur@partners.org FU Becton Dickinson/TriPath; Cytyc FX David C. Wilbur, M.D., received institutional grant support from Becton Dickinson/TriPath and Cytyc, and is a member of Becton Dickinson/TriPath Speakers' Bureau. NR 26 TC 2 Z9 2 U1 0 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD SEP-OCT PY 2008 VL 52 IS 5 BP 557 EP 562 DI 10.1159/000325597 PG 6 WC Pathology SC Pathology GA 352ON UT WOS:000259506700007 PM 18833817 ER PT J AU Beach, TG White, CL Hamilton, RL Duda, JE Iwatsubo, T Dickson, DW Leverenz, JB Roncaroli, F Buttini, M Hladik, CL Sue, LI Noorigian, JV Adler, CH AF Beach, Thomas G. White, Charles L. Hamilton, Ronald L. Duda, John E. Iwatsubo, Takeshi Dickson, Dennis W. Leverenz, James B. Roncaroli, Federico Buttini, Manuel Hladik, Christa L. Sue, Lucia I. Noorigian, Joseph V. Adler, Charles H. TI Evaluation of alpha-synuclein immunohistochemical methods used by invited experts SO ACTA NEUROPATHOLOGICA LA English DT Article ID LEWY-BODY-DISEASE; MULTIPLE SYSTEM ATROPHY; FORMIC-ACID PRETREATMENT; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; HUMAN-BRAIN; NACP/ALPHA-SYNUCLEIN; NEURODEGENERATIVE SYNUCLEINOPATHIES; PATHOLOGY; BODIES AB The use of alpha-synuclein immunohistochemistry has altered our concepts of the cellular pathology, anatomical distribution and prevalence of Lewy body disorders. However, the diversity of methodology between laboratories has led to some inconsistencies in the literature. Adoption of uniformly sensitive methods may resolve some of these differences. Eight different immunohistochemical methods for demonstrating alpha-synuclein pathology, developed in eight separate expert laboratories, were evaluated for their sensitivity for neuronal elements affected by human Lewy body disorders. Identical test sets of formalin-fixed, paraffin-embedded sections from subjects diagnosed neuropathologically with or without Lewy body disorders were stained with the eight methods and graded by three observers for specific and nonspecific staining. The methods did not differ significantly in terms of Lewy body counts, but varied considerably in their ability to reveal neuropil elements such as fibers and dots. One method was clearly superior for revealing these neuropil elements and the critical factor contributing to its high sensitivity was considered to be its use of proteinase K as an epitope retrieval method. Some methods, however, achieved relatively high sensitivities with optimized formic acid protocols combined with a hydrolytic step. One method was developed that allows high sensitivity with commercially available reagents. C1 [Beach, Thomas G.; Sue, Lucia I.] Sun Hlth Res Inst, Civin Lab Neuropathol, Sun City, AZ 85351 USA. [White, Charles L.; Hladik, Christa L.] Univ Texas Dallas, SW Med Ctr, Neuropathol Lab, Dallas, TX 75230 USA. [White, Charles L.; Hladik, Christa L.] Univ Texas Dallas, SW Med Ctr, Pathol Immunohistochem Lab, Dallas, TX 75230 USA. [Hamilton, Ronald L.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Duda, John E.; Noorigian, Joseph V.] Philadelphia Vet AVairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Iwatsubo, Takeshi] Univ Tokyo, Dept Life Pharmaceut, Tokyo, Japan. [Dickson, Dennis W.] Mayo Clin, Dept Lab Med & Pathol, Jacksonville, FL USA. [Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Leverenz, James B.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Roncaroli, Federico] Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, London, England. [Buttini, Manuel] Elan Pharmaceut, San Francisco, CA USA. [Adler, Charles H.] Mayo Clin, Dept Neurol, Scottsdale, AZ USA. RP Beach, TG (reprint author), Sun Hlth Res Inst, Civin Lab Neuropathol, 10515 W Santa Fe Dr, Sun City, AZ 85351 USA. EM thomas.beach@sunhealth.org OI Dickson, Dennis W/0000-0001-7189-7917 FU NIA NIH HHS [P30 AG019610, P30 AG019610-069002, P30 AG019610-079002, P30 AG019610-089002, P30 AG19610, P50 AG005133-25, P50 AG005136, P50 AG005136-25] NR 50 TC 78 Z9 78 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD SEP PY 2008 VL 116 IS 3 BP 277 EP 288 DI 10.1007/s00401-008-0409-8 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 334QB UT WOS:000258235200006 PM 18626651 ER PT J AU Cornelius, JR Kirisci, L Reynolds, M Homish, GG Clark, DB AF Cornelius, Jack R. Kirisci, Levent Reynolds, Maureen Homish, Gregory G. Clark, Duncan B. TI Husbands' SUD is associated with higher levels of co-occurring but not non-co-occurring psychiatric disorders among their wives SO ADDICTIVE BEHAVIORS LA English DT Article DE substance use disorders; psychiatric disorders; psychiatric symptoms ID SUBSTANCE USE DISORDERS; MARIJUANA USE AB Objective: Substance use among husbands has been shown to be associated with higher rates of substance use and of psychiatric symptoms among their wives. However, substance use disorders (SUD) and psychiatric disorders (as opposed to substance use or psychiatric symptoms) are rarely rigorously assessed among large samples of couples, so it is unclear whether SUD among husbands are associated with SUD among their wives, and whether the wives also display a higher prevalence of co-occurring or non-co-occurring psychiatric disorders. We compared the level of SUD, of co-occurring (with SUD) psychiatric disorders, and of non-co-occurring psychiatric diagnoses among the wives of males with SUDs vs among the wives of males without SUDs. We hypothesized that the presence of SUDs among males would be associated with a higher level of SUDs, of co-occurring psychiatric disorders, and of non-co-occurring psychiatric disorders in their wives. Method: The subjects in this study were the spouses of adult men with a lifetime history of an SUD (SUD+ husbands, N=342) vs those with no lifetime history of an SUD (SUD- husbands, N=350). These subjects were recruited for participation in a longitudinal project designed to elucidate the etiology of substance use disorders. Results: Co-occurring SUDs were five times more common among the spouses of SUD+ usbands than among the spouses of SUD- husbands (10.2% vs 2.0%, chi-square = 19.7, p=0.000). SUD/depressive disorder and SUD/anxiety disorder were both seven times more common among the spouses of SUD+ husbands than among the spouses of SUD- husbands (19.4% vs 4.7%, chi-square =45.8, p=0.000; 14.3% vs 2.0%, chi-square =34.5, p=0.000). In contrast, non-co-occurring depressive disorders and non-co-occurring anxiety disorders were not more common among the wives of the SUD+ husbands than among the SUD- husbands. Conclusions: These findings demonstrate that SUD and co-occurring psychiatric disorders (with SUD) are more common among the spouses of SUD+ husbands than among the spouses of SUD- husbands, but non-co-occurring ("pure") psychiatric disorders are not more common among the spouses of the SUD+ husbands. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Cornelius, Jack R.; Kirisci, Levent; Reynolds, Maureen; Clark, Duncan B.] Univ Pittsburgh, CEDAR, Pittsburgh, PA 15213 USA. [Cornelius, Jack R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Homish, Gregory G.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Hlth Behav, Buffalo, NY 14214 USA. [Homish, Gregory G.] SUNY Buffalo, Res Inst Addict, Buffalo, NY 14203 USA. RP Cornelius, JR (reprint author), 3811 OHara St, Pittsburgh, PA 15213 USA. EM corneliusjr@upmc.edu FU NIAAA NIH HHS [K24 AA15320, R01 AA015173, K24 AA015320, K02 AA00291, K02 AA000291, K24 AA015320-04, R01 AA013370, R01 AA013370-05, R01 AA015173-04]; NIDA NIH HHS [P50 DA005605, P50 DA05605, R01 DA019142-04, P50 DA005605-189002, R01 DA014635, R01 DA019142, R01 DA14635] NR 11 TC 4 Z9 4 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD SEP PY 2008 VL 33 IS 9 BP 1231 EP 1234 DI 10.1016/j.addbeh.2008.04.013 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 331XT UT WOS:000258046600019 PM 18544467 ER PT J AU Mimiaga, MJ Reisner, SL Vanderwarker, R Gaucher, MJ O'Connor, CA Medeiros, MS Safren, SA AF Mimiaga, Matthew J. Reisner, Sari L. Vanderwarker, Rodney Gaucher, Michael J. O'Connor, Catherine A. Medeiros, M. Susana Safren, Steven A. TI Polysubstance use and HIV/STD risk behavior among Massachusetts men who have sex with men accessing Department of Public Health mobile van services: Implications for intervention development SO AIDS PATIENT CARE AND STDS LA English DT Article ID BASE-LINE DATA; CLUB-DRUG-USE; HIV-INFECTION; METHAMPHETAMINE; CLIENTS; EXPLORE; STDS; GAY AB Polysubstance use has been posited to be a significant contributor to excess burden of HIV disease among men who have sex with men (MSM). The current Study investigated polysubstance use and sexual risk among men who utilize Massachusetts Department of Public Health (MDPH) van services (such as HIV, chlamydia, gonorrhea, or syphilis testing; Hepatitis A and B vaccinations) at venues targeting MSM. Participants (n = 214) completed a one-time, cross-sectional survey via an audio computer-assisted self-interview (ACASI) in English or Spanish between June 2007 and September 2007. Fifteen percent of the overall sample did not know their HIV status; 11% reported polysubstance use (concurrent use of three or more: poppers, ecstasy, GHB, cocaine, crystal methamphetamine, Viagra) during sex in the 12 months prior to study enrollment. Polysubstance users were more likely to be HIV infected (odds ratio [OR] = 4.62; p = 0.03) and to have a history of one or more sexually transmitted diseases (STDs; OR = 4.74; p = 0.03) relative to participants who did not report polysubstance use during sex. After controlling for covariates of age, race/ethnicity, education level, insurance status, sexual orientation, STD history,HIV status, and depression, multivariable logistic regression analyses revealed that polysubstance users were 9 times more likely to have reported unprotected anal (insertive or receptive) sex in the 12 months prior to Study enrollment (adjusted OR = 9.53; p = 0.007) compared to nonpolysubstance using MSM. Polysubstance users lacked access to care (21% were uninsured) and the overwhelming majority (96%) were first time users of mobile health van services. Accessible outreach services for MSM such as mobile van services need to include drug screening and interventions that triage men into treatment programs; year-round availability of van services is warranted. C1 [Mimiaga, Matthew J.; Reisner, Sari L.; Vanderwarker, Rodney; Safren, Steven A.] Fenway Inst, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Gaucher, Michael J.] Massachusetts Dept Publ Hlth, HIV AIDS Bur, Boston, MA USA. [O'Connor, Catherine A.] Northeastern Univ, Bouve Coll Hlth Sci, Sch Nursing, Boston, MA 02115 USA. [Medeiros, M. Susana] HIV Innovat, Project Hlth MOVES, Boston, MA USA. RP Mimiaga, MJ (reprint author), Fenway Inst, 7 Haviland St, Boston, MA 02115 USA. EM mmimiaga@fenwayhealth.org NR 35 TC 32 Z9 33 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD SEP PY 2008 VL 22 IS 9 BP 745 EP 751 DI 10.1089/apc.2007.0243 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 354LR UT WOS:000259641600008 PM 18754704 ER PT J AU Clark, A Mayben, JK Hartman, C Kallen, MA Giordano, TP AF Clark, April Mayben, Jennifer K. Hartman, Christine Kallen, Michael A. Giordano, Thomas P. TI Conspiracy beliefs about HIV infection are common but not associated with delayed diagnosis or adherence to care SO AIDS PATIENT CARE AND STDS LA English DT Article ID AFRICAN-AMERICANS; TRUST; HIV/AIDS; PROVIDERS; POPULATION; QUALITY; BARRIER AB We Sought to determine the prevalence of HIV conspiracy beliefs in patients with HIV and how those beliefs correlate with access and adherence to HIV care and health outcomes. From March to December 2005,113 patients at four public facilities in Houston, Texas, diagnosed with HIV for 3 years or less, participated in a cross-sectional Survey. Conspiracy beliefs were assessed with five items that dealt with HIV origin, cure, and vaccine. Medical records were reviewed for CD4 cell counts, HAART use, and appointment dates. Statistical analyses (including analysis of variance [ANOVA], chi(2) testing, and regression) determined the predictors of conspiracy beliefs and correlated them with outcomes. Sixty-three percent of the participants endorsed 1 or more conspiracy beliefs. African American patients more often held HIV conspiracy beliefs than white and other/mixed race patients (73%, 52'%, 47%; p = 0.045). Persons holding I or more conspiracy beliefs had higher CD4 cell counts at diagnosis (254 cells/mm(3) versus 92, p = 0.03); and similar rates of highly active antiretroviral therapy (HAART) use (73%, versus 71%), 100% adherence to HAART by self-report (53% versus 45%,), mean adherence by pharmacy refill (83% versuss 87%), and gaps in care greater than 120 days (49%, versus 53%), compared to subjects who did not hold any conspiracy beliefs (all p > 0.40). Since recruitment focused on patients in care, patients with extreme conspiracy beliefs may be underrepresented. Despite this, more than 50%, of the study population endorsed 1 or more conspiracy belief. However, these beliefs did not negatively impact access or adherence to HIV care. Efforts to improve adherence to HIV care may not need to focus on eliminating conspiracy beliefs. C1 [Clark, April; Mayben, Jennifer K.; Hartman, Christine; Kallen, Michael A.; Giordano, Thomas P.] Michael E DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. [Clark, April; Hartman, Christine; Kallen, Michael A.; Giordano, Thomas P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Mayben, Jennifer K.] Baylor Coll Med, Dept Community & Family Med, Houston, TX 77030 USA. RP Giordano, TP (reprint author), Michael E DeBakey VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tpg@bcm.tmc.edu FU National Institutes of Mental Health; National Institutes of Health [MH067505]; Agency for Healthcare Quality and Research [HP10031] FX The authors would like to thank Sallye M. Stapleton and Erick Villareal for their help in conducting the interviews. This work was suupported by the National Institutes of Mental Health, National Institutes of Health (Grant MH067505), the Agency for Healthcare Quality and Research (Grant HP10031), and the facilities and resources of the Michael E. DeBakey Veterans Affairs Medical Center and the Harris County Hospital District, Houston, Texas. NR 14 TC 17 Z9 17 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD SEP PY 2008 VL 22 IS 9 BP 753 EP 759 DI 10.1089/apc.2007.0249 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 354LR UT WOS:000259641600009 PM 18754706 ER PT J AU Mefford, ME Gorry, PR Kunstman, K Wolinsky, SM Gabuzda, D AF Mefford, Megan E. Gorry, Paul R. Kunstman, Kevin Wolinsky, Steven M. Gabuzda, Dana TI Bioinformatic prediction programs underestimate the frequency of CXCR4 usage by R5X4 HIV type 1 in brain and other tissues SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; V3 LOOP; CORECEPTOR USAGE; FUNCTIONAL-ANALYSIS; LYMPHOID-TISSUES; ENVELOPE; PHENOTYPE; INFECTION; AIDS; NEUROTROPISM AB Human immunodeficiency virus (HIV-1) variants in brain primarily use CCR5 for entry into macrophages and microglia, but dual-tropic (R5X4) HIV-1 has been detected in brain and cerebral spinal fluid (CSF) of some patients with HIV-associated dementia (HAD). Here, we sequenced the gp120 coding region of nine full-length dual-tropic (R5X4) env genes cloned directly from autopsy brain and spleen tissue from an AIDS patient with severe HAD. We then compiled a dataset of 30 unique clade B R5X4 Env V3 sequences from this subject and 16 additional patients (n = 4 brain and 26 lymphoid/blood) and used it to compare the ability of six bioinformatic algorithms to correctly predict CXCR4 usage in R5X4 Envs. Only one program (SVM(geno2pheno)) correctly predicted the ability of R5X4 Envs in this dataset to use CXCR4 with 90% accuracy (n = 27/30 predicted to use CXCR4). The PSSM(SINSI), Random Forest, and SVM(genomiac) programs and the commonly used charge rule correctly predicted CXCR4 usage with > 50% accuracy (22/30, 16/30, 19/30, and 25/30, respectively), while the PSSM(X4R5) matrix and "11/25" rule correctly predicted CXCR4 usage in < 50% of the R5X4 Envs (10/30 and 13/30, respectively). Two positions in the V3 loop (19 and 32) influenced coreceptor usage predictions of nine R5X4 Envs from patient MACS1 and a total of 12 Envs from the dataset (40% of unique V3 sequences). These results demonstrate that most predictive algorithms underestimate the frequency of R5X4 HIV-1 in brain and other tissues. SVM(geno2pheno) is the most accurate predictor of CXCR4 usage by R5X4 HIV-1. C1 [Mefford, Megan E.; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Gorry, Paul R.] Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. [Gorry, Paul R.] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. [Kunstman, Kevin; Wolinsky, Steven M.] Northwestern Univ, Sch Med, Chicago, IL 60611 USA. [Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 816,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NIH [NS37277, MH83588, 1F31NS060611-01]; Australian National Health and Medical Research Council (NHMRC); Australian NHMRC [433915]; Harvard Medical School Center for AIDS Research (CFAR); DFCI/Harvard Cancer Center FX We thank Mark Jensen for helpful discussions. This work was supported by NIH Grants NS37277 and MH83588. M. M. was supported in part by NIH fellowship 1F31NS060611-01. P. R. G. is the recipient of an Australian National Health and Medical Research Council (NHMRC) R. Douglas Wright Biomedical Career Development Award and was supported, in part, by a grant from the Australian NHMRC (433915). Core facilities were supported by Harvard Medical School Center for AIDS Research (CFAR) and DFCI/Harvard Cancer Center grants. NR 22 TC 22 Z9 22 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 2008 VL 24 IS 9 BP 1215 EP 1220 DI 10.1089/aid.2008.0009 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 351UA UT WOS:000259450200012 PM 18788913 ER PT J AU Durazzo, TC Rothlind, JC Gazdzinski, S Meyerhoff, DJ AF Durazzo, Timothy C. Rothlind, Johannes C. Gazdzinski, Stefan Meyerhoff, Dieter J. TI The relationships of sociodemographic factors, medical, psychiatric, and substance-misuse co-morbidities to neurocognition in short-term abstinent alcohol-dependent individuals SO ALCOHOL LA English DT Review DE alcohol use disorders; alcohol dependence; cigarette smoking; age effects; co-morbidities ID CHRONIC CIGARETTE-SMOKING; ANTISOCIAL PERSONALITY-DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; CHRONIC HEPATITIS-C; DSM-IV ALCOHOL; MAJOR DEPRESSION; NEUROPSYCHOLOGICAL DEFICITS; COGNITIVE EFFICIENCY; PROCESSING-SPEED; RESONANCE-SPECTROSCOPY AB Co-morbidities that commonly accompany those afflicted with an alcohol use disorder (AUD) may promote variability in the pattern and magnitude of neurocognitive abnormalities demonstrated. The goal of this study was to investigate the influence of several common co-morbid medical conditions (primarily hypertension and hepatitis Q, psychiatric (primarily unipolar mood and anxiety disorders), and substance use (primarily psychostimulant and cannabis) disorders, and chronic cigarette smoking on the neurocognitive functioning in short-term abstinent, treatment-seeking individuals with AUD. Seventy-five alcohol -dependent participants (ALC; 51 +/- 9 years of age; three females) completed comprehensive neurocognitive testing after approximately I month of abstinence. Multivariate multiple linear regression evaluated the relationships among neurocognitive variables and medical conditions, psychiatric, and substance-use disorders, controlling for sociodemographic factors. Sixty-four percent of ALC had at least one medical, psychiatric, or substance-abuse co-morbidity (excluding smoking). Smoking status (smoker or nonsmoker) and age were significant independent predictors of cognitive efficiency, general intelligence, postural stability, processing speed, and visuospatial memory after age-normed adjustment and control for estimated premorbid verbal intelligence, education, alcohol consumption, and medical, psychiatric, and substance-misuse co-morbidities. Results indicated that chronic smoking accounted for a significant portion of the variance in the neurocognitive performance of this middle-aged AUD cohort. The age-related findings for ALC suggest that alcohol dependence, per se, was associated with diminished neurocognitive functioning with increasing age. The study of participants who demonstrate common co-morbidities observed in AUD is necessary to fully understand how AUD, as a clinical syndrome, affects neurocognition, brain neurobiology, and their changes with extended abstinence. (C) 2008 Elsevier Inc. All rights reserved. C1 [Durazzo, Timothy C.; Rothlind, Johannes C.; Gazdzinski, Stefan; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Rothlind, Johannes C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, 114M 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU NIH [AA10788] FX This project was supported by NIH AA10788 (DJ-M). We thank the San Francisco VA Medical Center Research Service for logistical support; Mary Rebecca Young and Bill Clift of the VA Substance Abuse Day Hospital; and Drs. David Pating, Peter Washburn, and Karen Moise and their colleagues at the Kaiser Permanente Chemical Dependency Recovery Program for their valuable assistance in recruiting participants. We also wish to extend our gratitude to the study participants, who made this research possible. NR 118 TC 16 Z9 16 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD SEP PY 2008 VL 42 IS 6 BP 439 EP 449 DI 10.1016/j.alcohol.2008.06.001 PG 11 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 352NE UT WOS:000259503100001 PM 18760713 ER PT J AU Braithwaite, RS Conigliaro, J McGinnis, KA Maisto, SA Bryant, K Justice, AC AF Braithwaite, R. Scott Conigliaro, Joseph McGinnis, Kathleen A. Maisto, Stephen A. Bryant, Kendall Justice, Amy C. TI Adjusting alcohol quantity for mean consumption and intoxication threshold improves prediction of nonadherence in HIV patients and HIV-negative controls SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE human immunodeficiency virus; alcohol; nonadherence ID OLDER-ADULTS; PRIMARY-CARE; ADHERENCE; DRINKING; DRINKERS; VETERANS; RELIABILITY; TOXICITY; OUTCOMES; FRAILTY AB Background: Screening for hazardous drinking may fail to detect a substantial proportion of individuals harmed by alcohol. We investigated whether considering an individual's usual drinking quantity or threshold for alcohol-induced cognitive impairment improves the prediction of nonadherence with prescribed medications. Method: Cross-sectional analysis of participants in a large, multi-site cohort study. We used the timeline followback to reconstruct 30-day retrospective drinking histories and the timeline followback modified for adherence to reconstruct 30-day medication adherence histories among 3,152 individuals in the Veterans Aging Cohort Study, 1,529 HIV infected and 1,623 uninfected controls. We categorized daily alcohol consumption by using quantity alone, quantity after adjustment for the individual's mean daily alcohol consumption, and self-reported level of impairment corresponding to each quantity. A standard drink was defined as 14 g of ethanol. Nonadherence was defined as the proportion of days with >= 1 medication doses missed or taken >= 2 hours late, and clinically significant nonadherence was defined as >= 5% absolute increase in the proportion of days with nonadherence. Results: The mean adjusted- and impairment-based methods showed greater discrimination of nonadherence risk compared to the measure based on quantity alone (quantity-based categorization, 3.2-fold increase; quantity adjusted for mean daily consumption, 4.6-fold increase, impairment-based categorization, 3.6-fold increase). The individualized methods also detected greater numbers of days with clinically significant nonadherence associated with alcohol. Alcohol was associated with clinically significant nonadherence at a lower threshold for HIV infected versus uninfected patients (2 standard drinks vs. 4 standard drinks) using quantity-based categorization, but this difference was no longer apparent when individualized methods were used. Conclusions: Tailoring screening questions to an individual's usual level of alcohol consumption or threshold for impairment improves the ability to predict alcohol-associated medication nonadherence. C1 [Braithwaite, R. Scott; Justice, Amy C.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, West Haven, CT 06516 USA. [Braithwaite, R. Scott; Justice, Amy C.] Connecticut Vet Adm Med Ctr, West Haven, CT USA. [Conigliaro, Joseph] Univ Kentucky, Dept Med, Gen Internal Med Sect, Lexington, KY 40506 USA. [McGinnis, Kathleen A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Maisto, Stephen A.] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Bryant, Kendall] NIAAA, NIH, Bethesda, MD USA. RP Braithwaite, RS (reprint author), Yale Univ, Sch Med, Dept Gen Internal Med, VA Connecticut Healthcare Syst, 11ACSLG,950 Campbell Ave, West Haven, CT 06516 USA. EM ronald.braithwaite@med.va.gov FU National Institute of Alcohol Abuse and Alcoholism [K23 AA14483-01, R21 AA015894-01] FX This work was funded by Grants K23 AA14483-01 and R21 AA015894-01 from the National Institute of Alcohol Abuse and Alcoholism. This study was approved by the Yale University and West Haven VA Institutional Review Boards. NR 25 TC 25 Z9 26 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2008 VL 32 IS 9 BP 1645 EP 1651 DI 10.1111/j.1530-0277.2008.00732.x PG 7 WC Substance Abuse SC Substance Abuse GA 341PN UT WOS:000258726700015 PM 18616666 ER PT J AU Sheinkopf, LE Rafi, AW Do, LT Katz, RM Klaustermeyer, WB AF Sheinkopf, Lee E. Rafi, Asif W. Do, LanAnh T. Katz, Roger M. Klaustermeyer, William B. TI Efficacy of omalizumab in the treatment of atopic dermatitis: A pilot study SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article DE Anti-IgE; asthma; atopic dermatitis; biologic therapeutic; IgE; investigator global assessment; omalizumab; prospective; treatment ID ANTIIMMUNOGLOBULIN-E THERAPY; ANTI-IGE THERAPY; TACROLIMUS OINTMENT 0.03-PERCENT; EPIDERMAL LANGERHANS CELLS; LONG-TERM MANAGEMENT; FC-EPSILON-RI; ALLERGIC-ASTHMA; IMMUNOLOGICAL MECHANISMS; PIMECROLIMUS CREAM; SCORAD INDEX AB Omalizumab is a unique biologic therapeutic drug approved for treating atopic patients with moderate to severe persistent allergic asthma with a serum IgE ranging from 30 to 700 IU/mL. This study was performed to examine the efficacy of omalizumab for the treatment of atopic dermatitis (AD), a disease with siginificant morbidity. A prospective analysis was performed to assess the efficacy of omalizumab in 21 patients with moderate to severe persistent allergic asthma and AD. Patients were stratified into the following groups: very high IgE (> 700 IU/mL), high IgE (186-700 IU/mL), and normal IgE (0-185 IU/mL). AD severity was assessed at 0, 1, 3, 6, and 9 months via 0)7 Investigator Global Assessment index. Twenty-one patients (14-64 years old) were evaluated. Pretreatment IgE levels ranged from 18.2 to 8396 IU/mL, (mean IgE level was 1521. IU/mL). All 21 patients showed clinical and statistically significant improvement of their atopic dermatitis (p < 0.00052). In conclusion, this study indicates that omnalizumab is effective in treating AD in patients with moderate to severe persistent allergic asthma. C1 [Sheinkopf, Lee E.; Klaustermeyer, William B.] Univ Calif Los Angeles, Dept Allergy & Immunol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Rafi, Asif W.; Do, LanAnh T.; Katz, Roger M.] Allergy Asthma Care Ctr Inc, Los Angeles, CA USA. RP Sheinkopf, LE (reprint author), Univ Calif Los Angeles, Dept Allergy & Immunol, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 111R, Los Angeles, CA 90073 USA. NR 46 TC 76 Z9 80 U1 1 U2 2 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 SEP-OCT PY 2008 VL 29 IS 5 BP 530 EP 537 DI 10.2500/aap.2008.29.3160 PG 8 WC Allergy SC Allergy GA 358JA UT WOS:000259911800016 PM 18926061 ER PT J AU Perrin, JM AF Perrin, James M. TI Prevention and chronic health conditions among children and adolescents SO AMBULATORY PEDIATRICS LA English DT Editorial Material ID CARE NEEDS; CHILDHOOD; SERVICES C1 Harvard Univ, MassGen Hosp Children, Sch Med, Ctr Child & Adolescent Hlth Policy,Dept Pediat, Boston, MA 02114 USA. RP Perrin, JM (reprint author), Harvard Univ, MassGen Hosp Children, Sch Med, Ctr Child & Adolescent Hlth Policy,Dept Pediat, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM jperrin@partners.org NR 17 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD SEP-OCT PY 2008 VL 8 IS 5 BP 271 EP 272 DI 10.1016/j.ambp.2008.08.003 PG 2 WC Pediatrics SC Pediatrics GA 356NL UT WOS:000259784800001 PM 18922497 ER PT J AU Van Cleave, J Davis, MM AF Van Cleave, Jeanne Davis, Matthew M. TI Preventive care utilization among children with and without special health care needs: Associations with unmet need SO AMBULATORY PEDIATRICS LA English DT Article DE children with special health care needs; dental care; preventive care; unmet need ID CHRONIC DISEASE; UNITED-STATES; DENTAL-CARE; SERVICES; GUIDELINES; DELIVERY; ILLNESS; CLINICS; VISITS; RATES AB Objective.-To compare attendance at preventive medical and dental visits for children with special health care needs (CSHCN) and children without special health care needs, and associations between attending visits and unmet need. Methods.-We analyzed data on 102 353 children aged 0 to 17 years from the National Survey of Children's Health. We examined associations between attending preventive medical or dental visits and CSHCN status, and unmet need for medical or preventive dental care and attending preventive medical or dental visits. Results.-Medical care-CSHCN were more likely than other children to attend a well-child visit (odds ratio [95% confidence interval], 1.45 [1.12-1.93] for 0 to 5 years, 1.99 [1.74-2.28] for 6 to I I years, 1.84 [1.64-2.06] for 12 to 17 years). CSHCN aged 12 to 17 years attending a well-child visit had lower odds of unmet medical need (0.48 [0.27-0.85]) than CSHCN not attending visits; well-child visits and unmet need were not associated for Younger age groups. Dental care-CSHCN aged 3 to 5 years were more likely than other children of similar ages to attend a preventive dental visit (1.26 [1.04-1.52]). CSHCN attending a preventive dental visit had lower odds of unmet preventive dental needs than CSHCN not attending visits (0.52 [0.28-0.93] for 3 to 5 years, 0.18 [0.12-0.28] for 6 to 11 years, 0. 12 [0.08-0.17] for 12 to 17 years). Conclusions.-CSHCN attend preventive medical and dental visits at similar or higher rates than other children. CSHCN who attend visits are less likely to have unmet needs. Further research should examine differences in visit content for CSHCN and mechanisms whereby preventive care may reduce unmet need. C1 [Van Cleave, Jeanne] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. [Davis, Matthew M.] Univ Michigan, Child Hlth Evaluat & Res Unit, Div Gen Pediat, Ann Arbor, MI 48109 USA. [Davis, Matthew M.] Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA. [Davis, Matthew M.] Univ Michigan, Gerald R Ford Sch Publ Policy, Ann Arbor, MI 48109 USA. RP Van Cleave, J (reprint author), 50 Staniford St 901, Boston, MA 02114 USA. EM jvancleave@partners.org FU Robert Wood Johnson Clinical Scholars Program at the University of Michigan FX Supported in part by Robert Wood Johnson Clinical Scholars Program at the University of Michigan. NR 29 TC 35 Z9 36 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD SEP-OCT PY 2008 VL 8 IS 5 BP 305 EP 311 DI 10.1016/j.ambp.2008.04.003 PG 7 WC Pediatrics SC Pediatrics GA 356NL UT WOS:000259784800008 PM 18922504 ER PT J AU Alexander, D On, FS Roe, MT Pollack, CV Ohman, EM Cannon, CP Gibler, WB Fintel, DJ Peterson, ED Brown, DL AF Alexander, Deepu On, Fang-Shu Roe, Matthew T. Pollack, Charles V. Ohman, E. Magnus Cannon, Christopher P. Gibler, W. Brian Fintel, Dan J. Peterson, Eric D. Brown, David L. TI Use of and in hospital outcomes after early clopidogrel therapy in patients not undergoing an early invasive strategy for treatment of non-ST-segment elevation myocardial infarction: Results from Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines (CRUSADE) SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; PLATELET GLYCOPROTEIN IIB/IIIA; ARTERY-BYPASS SURGERY; TASK-FORCE; INTERVENTION; INHIBITION; TIROFIBAN; COMMITTEE; ASPIRIN; SCORE AB Background Although current guidelines recommend early initiation of clopidogrel in patients with non-ST-segment elevation myocardial infarction (NSTEMI), the degree to which it has been adopted in clinical practice remains unclear. We sought to determine patterns of early (< 24 hours of arrival) clopidogrel use and its association with clinical outcomes in patients with NSTEMI not undergoing early percutaneous intervention (PCI). Methods Using data from the CRUSADE initiative, after the exclusion of patients who underwent PCI within 24 hours of arrival, we studied trends in early clopidogrel use among 93,045 patients with NSTEMI. Multivariable logistic regression models were used to determine the association between early clopidogrel treatment and inhospital outcomes. Results A total of 38.6% of the NSTEMI patients not undergoing PCI within 24 hours of arrival received early clopidogrel. Adjusted inhospital mortality rate was lower in the early clopidogrel group compared to the group that did not receive it on admission (odds ratio 0.68, 95% CI 0.61-0.77). The rate of major bleeding in patients not undergoing coronary artery bypass surgery was similar among the groups treated with and without early clopidogrel (9.5% vs 9.5%, P = .90). Conclusions Until recently, up to 50% of NSTEMI patients in contemporary practice in the United States not undergoing PCI within 24 hours of arrival in the United States are not treated according to guideline recommendations. Among a high-risk NSTEMI population not undergoing PCI within 24 hours of arrival, the nonrandomized short-term use of clopidogrel is associated with a lower risk of inhospital mortality without an increased risk of major bleeding. C1 [Brown, David L.] SUNY Stony Brook, Sch Med, Div Cardiovasc Med, Hlth Sci Ctr T16 080, Stony Brook, NY 11794 USA. [On, Fang-Shu; Roe, Matthew T.; Ohman, E. Magnus; Peterson, Eric D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Pollack, Charles V.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Gibler, W. Brian] Univ Cincinnati, Coll Med, Dept Emergency Med, Cincinnati, OH USA. [Fintel, Dan J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Brown, DL (reprint author), SUNY Stony Brook, Sch Med, Div Cardiovasc Med, Hlth Sci Ctr T16 080, Stony Brook, NY 11794 USA. EM david.brown@stonybrook.edu NR 17 TC 24 Z9 26 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2008 VL 156 IS 3 BP 606 EP 612 DI 10.1016/j.ahj.2008.05.012 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 346DQ UT WOS:000259049000030 PM 18760147 ER PT J AU Stein, R Gupta, B Agarwal, S Golub, J Bhutan, D Rosman, A Eng, C AF Stein, Russell Gupta, Bhanu Agarwal, Sanjay Golub, Jason Bhutan, Divaya Rosman, Alan Eng, Calvin TI Prognostic implications of normal (< 0.10 ng/ml) and borderline (0.10 to 1.49 ng/ml) troponin elevation levels in critically ill patients without acute coronary syndrome SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID I LEVELS; MYOCARDIAL-INFARCTION; RISK-FACTOR; MORTALITY; PREDICT; SCORE AB Borderline increase of troponin I (cTnI) is associated with higher rates of cardiovascular events compared with normal levels in the setting of acute coronary syndrome (ACS), but the significance of borderline cTnI levels in patients without chest pain may differ. The aim of this study was to determine the prognostic implications of intermediate serum cTnI levels in patients without ACS in the intensive care unit (ICU). This was a 12-month retrospective study of 240 patients without ACS in the ICU with normal (<0.1 ng/ml) or intermediate (0.1 to 1.49 ng/ml) cTnI levels. End points included in-hospital mortality, lengths of ICU and hospital stays, and rates of postdischarge readmission and mortality. Overall in-hospital mortality was 13%, with 5% in the normal cTnI group and 28% in the intermediate cTnI group. By multivariate analysis, intermediate cTnI was independently associated with in-hospital mortality (p = 0.004) and length of ICU stay (p = 0.028). The only other independent risk factor for inpatient mortality was a standardized ICU prognostic measurement (Simplified Acute Physiology Score 11 score). Intermediate cTnI had no prognostic implications regarding length of hospital stay, readmission rate, or postdischarge mortality at 6 months. In conclusion, an intermediate level of cTnI in patients without ACS in the ICU is an independent prognostic marker predicting in-hospital mortality and length of ICU stay. Patients with intermediate cTnI levels who survive to discharge have equivalent out-of-hospital courses for up to 6 months compared with patients with normal cTnI levels. (C) 2008 Elsevier Inc. All rights reserved. C1 [Stein, Russell] Mt Sinai Med Ctr, Zena & Michael A Wietner Cardiovasc Inst, New York, NY 10029 USA. [Stein, Russell] Mt Sinai Med Ctr, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, New York, NY 10029 USA. [Gupta, Bhanu; Agarwal, Sanjay; Bhutan, Divaya; Rosman, Alan; Eng, Calvin] Bronx Vet Affairs Med Ctr, Cardiol Sect, Bronx, NY USA. [Gupta, Bhanu; Agarwal, Sanjay; Bhutan, Divaya; Rosman, Alan; Eng, Calvin] Bronx Vet Affairs Med Ctr, Med Serv, Bronx, NY USA. [Golub, Jason] Jacobi Med Ctr, Dept Med, Bronx, NY USA. RP Stein, R (reprint author), Mt Sinai Med Ctr, Zena & Michael A Wietner Cardiovasc Inst, New York, NY 10029 USA. EM Russell.Stein@mssm.edu NR 13 TC 27 Z9 27 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 2008 VL 102 IS 5 BP 509 EP 512 DI 10.1016/j.amjcard.2008.04.026 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 342LB UT WOS:000258784500001 PM 18721503 ER PT J AU Steinberg, BA French, WJ Peterson, E Frederick, PD Cannon, CP AF Steinberg, Benjamin A. French, William J. Peterson, Eric Frederick, Paul D. Cannon, Christopher P. CA Natl Registry Myocardial Infarctio TI Is coding for myocardial infarction more accurate now that coding descriptions have been clarified to distinguish ST-elevation myocardial infarction from non-ST elevation myocardial infarction? SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; SEGMENT ELEVATION; TASK-FORCE; MANAGEMENT; REGISTRY AB Outcomes are typically graded on the basis of diagnoses coded according to the International Classification of Diseases, Ninth Revision (ICD-9). To facilitate performance measurement, the ICD-9 codes for acute myocardial infarction changed in October 2005 to completely separate non-ST elevation myocardial infarction (NSTEMI; code 410.71) and ST elevation myocardial infarction (STEMI; all other codes 410.x), yet it is unclear whether these changes have been implemented by coders. Patients in the National Registry of Myocardial Infarction (NRMI), version S, were categorized in 2 ways: by electrocardiographic (ECG) findings and ICD-9 codes. Agreement between ECG findings and ICD-9 codes for type of myocardial infarction (STEMI or NSTEMI) was assessed before and after ICD-9 revision. Mortality rates were measured in a subgroup of patients discharged without transfer after the coding change. There were 102,679 hospitalizations before October 2005 and 63,012 hospitalizations after the coding change, among which the mean age was 66.7 years. Previously, 81% of NSTEMIs (by ECG diagnosis) were coded ICD-9 410.71; after the reclassification of code 410.71 to reflect NSTEMI, 82% of NSTEMIs were coded 410.71 (p < 0.001). Overall, the correlation of ECG diagnosis with ICD-9 code improved only slightly after the coding change. In conclusion, despite more distinctly separated definitions of STEMI and NSTEMI in the new ICD-9 coding system as of October 2005, there appears to be little change in coding, which may reflect a lack of awareness of this substantial change in classification. (C) 2008 Elsevier Inc. All rights reserved. C1 [Steinberg, Benjamin A.] Johns Hopkins Sch Med, Baltimore, MD USA. [French, William J.] Harbor UCLA Med Ctr, Div Cardiol, Torrance, CA 90509 USA. [Peterson, Eric] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Frederick, Paul D.] Ovat Res Grp, Seattle, WA USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Johns Hopkins Sch Med, Baltimore, MD USA. EM cpcannon@partners.org OI Frederick, Paul/0000-0002-7936-5488 NR 13 TC 16 Z9 16 U1 0 U2 4 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 SEP 1 PY 2008 VL 102 IS 5 BP 513 EP 517 DI 10.1016/j.amjcard.2008.04.039 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 342LB UT WOS:000258784500002 PM 18721504 ER PT J AU Brilakis, ES de Lemos, JA Cannon, CP Wiviott, SD Murphy, SA Morrow, DA Sabatine, MS Banerjee, S Blazing, MA Califf, RM Braunwald, E AF Brilakis, Emmanouil S. de Lemos, James A. Cannon, Christopher P. Wiviott, Stephen D. Murphy, Sabina A. Morrow, David A. Sabatine, Marc S. Banerjee, Subhash Blazing, Michael A. Califf, Robert M. Braunwald, Eugene TI Outcomes of patients with acute coronary syndrome and previous coronary artery bypass grafting (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy [PROVE IT-TIMI 22] and the Aggrastat to Zocor [A to Z] trials) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LIPOPROTEIN CHOLESTEROL LEVELS; UNSTABLE ANGINA-PECTORIS; LOW-DOSE ANTICOAGULATION; PERCUTANEOUS INTERVENTIONS; MYOCARDIAL-INFARCTION; GLYCOPROTEIN IIB/IIIA; FOLLOW-UP; SURGERY; ATHEROSCLEROSIS; PREVENTION AB We examined the effects of intensive statin therapy in patients with acute coronary syndromes (ACSs) and previous coronary artery bypass graft surgery (CABG) participating in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE-IT TIMI 22) and the Aggrastat to Zocor (A to Z) trials. Of the 8,655 patients enrolled in PROVE IT-TIMI 22 or A to Z, 640 (7.4%) had undergone CABG before enrollment. After a median follow-up of 2 years, compared with patients without previous CABG, those with previous CABG had a higher risk of cardiovascular death (6.2% vs 2.8% myocardial infarction (14.2% vs 6.6% and readmission for ACS (7.9% vs 4.4%, p < 0.001 for all comparisons) but a lower rate of repeat coronary revascularization (22.7% vs 26.9%, p = 0.01). Compared with moderate statin therapy, intensive statin therapy appeared to decrease the composite of cardiovascular death, myocardial infarction, stoke, and readmission for an ACS (A to Z primary end point) to a similar extent in patients with (26.1% vs 21.6%, hazard ratio 0.84, p = 0.27) and without (13.9% vs 12.0%, hazard ratio 0.86, p = 0.016) previous CABG, although the decrease was not statistically significant in the previous CABG group, likely due to the small number of patients with previous CABG. In conclusion, compared with patients with ACS without previous CABG, those with previous CABG have a higher risk for adverse cardiac events and may derive similar benefit from intensive statin therapy. (C) 2008 Elsevier Inc. All rights reserved. C1 [Brilakis, Emmanouil S.; de Lemos, James A.; Banerjee, Subhash] Univ Texas SW Med Ctr Dallas, Div Cardiovasc, Dept Med, Dallas, TX 75390 USA. [Brilakis, Emmanouil S.; Banerjee, Subhash] Dallas VA Med Ctr, Dallas, TX USA. [Cannon, Christopher P.; Wiviott, Stephen D.; Murphy, Sabina A.; Morrow, David A.; Sabatine, Marc S.; Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Blazing, Michael A.; Califf, Robert M.] Duke Clin Res Inst, Durham, NC USA. RP Brilakis, ES (reprint author), Univ Texas SW Med Ctr Dallas, Div Cardiovasc, Dept Med, Dallas, TX 75390 USA. EM eminanouil.brilakis@utsouthwestern.edu RI Brilakis, Emmanouil/B-5282-2009; OI Brilakis, Emmanouil/0000-0001-9416-9701 FU Bristol-Myers Squibb Co. (Princeton, New Jersey); Sankyo Pharma. Inc. (Parsippany, New Jersey); Merck & Co.. Inc. (West Point, Pennsylvania); Merck-Schering-Plough Corp. (Kenilworth, New Jersey); Pfizer. Inc. (New York. New York); Eli Lilly & Co. (Indianapolis. Indiana); Sankyo Pharma, Inc.,; AstraZeneca, Sanofi-Aventis, Inc.,; CV Therapeutics. Inc., Palo Alto, California; Massachussets, Schering-Plough Corp. (Kenilworth. New Jersey); Schering-Plough Corp.,; Novartis Pharmaceuticals Corp. (East Hanover, New Jersey) FX Pravastatin or Atorvastitin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 was funded by Bristol-Myers Squibb Co. (Princeton, New Jersey) and Sankyo Pharma. Inc. (Parsippany, New Jersey) and Aggrastat to Zocor was funded by Merck & Co.. Inc. (West Point, Pennsylvania). Dr. de Lemos has received research grant Support from Merck & Co., Inc., and has served on speakers' bureaus for Merck & Co.. Inc., Merck-Schering-Plough Corp. (Kenilworth, New Jersey). and Pfizer. Inc. (New York. New York). Dr. Cannon has received research grant support from Bristol-Myers Squibb Co., Sanofi-Aventis. Inc. (New York. New York), and Merck & Co.. Inc., and consulting fees from AstraZeneca (Wilmington, Delaware), GlaxoSmithKline (Research Triangle Park, North Carolina). and Pfizer. Inc. Dr. Wiviott has received research Support from Eli Lilly & Co. (Indianapolis. Indiana) and Sankyo Pharma, Inc., and honoraria for lectures from Pfizer, Inc. Dr. Murphy currently receives research grant support from AstraZeneca, Sanofi-Aventis, Inc., CV Therapeutics. Inc., Palo Alto, California, Eli Lilly & Co., Millennium, Cambridge, Massachussets, Schering-Plough Corp. (Kenilworth. New Jersey), Nuvelo, San Carlos, California, Pfizer. Inc., Inotek, Beverly, Massachussetts, and Merck & Co.. Inc., and previously from Bristol-Myers Squibb Co. Dr. Morrow has received research grants and honoraria from Sanofi-Aventis. Dr. Sabatine has served as consultant and on scientific advisory boards for Bristol-Myers Squibb Co. and Sanofi-Aventis. Dr. Blazing has received research grant support from Merck & Co., Inc., and Merck-Schering Plough and has served on speakers' bureaus for Pfizer. Inc., and Merck & Co., Inc. Dr. Califf has received major research grant support from and has had institutional relationships with Merck & Co., Inc., Schering-Plough Corp.. Pfizer, Inc., Novartis Pharmaceuticals Corp. (East Hanover, New Jersey), and Bristol-Myers Squibb. Dr. Braunwald has received research support from Bristol-Myers Squibb Co., Merck & Co., Inc., and AstraZeneca and honoraria for lectures from Bristol-Myers Squibb Co., Sanofi-Aventis, Inc., and Pfizer. Inc. NR 29 TC 31 Z9 34 U1 0 U2 3 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 SEP 1 PY 2008 VL 102 IS 5 BP 552 EP 558 DI 10.1016/j.amjcard.2008.04.024 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 342LB UT WOS:000258784500009 PM 18721511 ER PT J AU Danik, S Neuzil, P d'Avila, A Malchano, ZJ Kralovec, S Ruskin, JN Reddy, VY AF Danik, Stephan Neuzil, Petr d'Avila, Andre Malchano, Zachary J. Kralovec, Stepan Ruskin, Jeremy N. Reddy, Vivek Y. TI Evaluation of catheter ablation of periatrial ganglionic plexi in patients with atrial fibrillation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID AUTONOMIC NERVOUS-SYSTEM; PULMONARY VEIN ISOLATION; HEART-RATE; MECHANISM; ARRHYTHMIAS; EXCITATION; CONDUCTION; ANATOMY; LENGTH AB Recent data suggests that the cardiac autonomic nervous system has an important role in the initiation and maintenance of atrial fibrillation (AF). This study investigated (1) the feasibility of identifying and targeting these autonomic ganglia using endocardial radio-frequency stimulation and ablation, respectively; (2) the efficacy of endocardial ablation to completely eliminate the vagal response elicited from epicardial stimulation; and (3) the effect of autonomic ablation on the acute inducibility of AF. The study included 18 patients referred for catheter ablation of suspected vagal-mediated AF. The endocardial left atrial surface was stimulated at high frequency (20 to 50 Hz) to elicit a vagal response. In selected patients (n = 5), pericardial access was obtained using a subxyphoid puncture to permit epicardial stimulation. Catheter ablation of the putative autonomic ganglionic sites was performed from the left atrial endocardium using irrigated radiofrequency energy. After ablation of all identifiable autonomic ganglia, high-frequency pacing was repeated to induce AF. In all patients, stimulation at certain endocardial sites elicited a vagal response. Endocardial ablation abrogated this vagal responsiveness. Furthermore, for sites accessible from the pericardium, the vagal response elicited using epicardial stimulation was also eliminated. Despite successful ablation of these ganglia, AF was still inducible in 17 of 18 patients. In conclusion, successful ablation of autonomic ganglia from an endocardial approach can be reliably achieved using an irrigated catheter. In addition, ablation of these structures in patients with vagal-mediated AF is insufficient to prevent its acute reinduction with high-frequency atrial stimulation. (C) 2008 Elsevier Inc. All rights reserved. C1 [Danik, Stephan; d'Avila, Andre; Malchano, Zachary J.; Ruskin, Jeremy N.; Reddy, Vivek Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Neuzil, Petr; Kralovec, Stepan] Na Homolce Hosp, Cardiac Arrhythmia Serv, Prague, Czech Republic. RP Danik, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM sdanik@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; FU National Institutes of Health, Bethesda, Maryland [HL68064-02] FX Dr. Reddy was supported by a K23 award (HL68064-02) from the National Institutes of Health, Bethesda, Maryland. NR 28 TC 28 Z9 32 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 SEP 1 PY 2008 VL 102 IS 5 BP 578 EP 583 DI 10.1016/j.amjcard.2008.04.064 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 342LB UT WOS:000258784500013 PM 18721515 ER PT J AU Sobhani, K Bankson, DD AF Sobhani, Kimia Bankson, Daniel D. TI Can reflexive testosterone testing improve service and decrease costs? SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Academy-of-Clinical-Laboratory-Physicians-and-Scientists CY JUN 05-07, 2008 CL Philadelphia, PA SP Acad Clin Lab Phys & Sci C1 [Sobhani, Kimia; Bankson, Daniel D.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Bankson, Daniel D.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2008 VL 130 IS 3 BP 477 EP 478 PG 2 WC Pathology SC Pathology GA 338WA UT WOS:000258538900042 ER PT J AU Roehrl, MHA Rho, JH Wang, JY AF Roehrl, Michael H. A. Rho, Jung-hyun Wang, Julia Y. TI Proteomic expression analysis of surgical human colorectal cancer tissues: Up-regulation of PSB7, PRDX1, and SRP09 and biomarkers of hypoxic adaptation in cancer SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Academy-of-Clinical-Laboratory-Physicians-and-Scientists CY JUN 05-07, 2008 CL Philadelphia, PA SP Acad Clin Lab Phys & Sci C1 [Roehrl, Michael H. A.] Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. [Rho, Jung-hyun; Wang, Julia Y.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Roehrl, Michael H. A.; Rho, Jung-hyun; Wang, Julia Y.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2008 VL 130 IS 3 MA 33 BP 479 EP 480 PG 2 WC Pathology SC Pathology GA 338WA UT WOS:000258538900047 ER EF