FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hiasa, Y Tokumoto, Y Konishi, I Matsuura, B Michitaka, K Chung, RT Onji, M AF Hiasa, Yoichi Tokumoto, Yoshio Konishi, Ichiro Matsuura, Bunzo Michitaka, Kojiro Chung, Raymond T. Onji, Morikazu TI ME3738 inhibits hepatitis C virus replication by enhancing interferon-beta SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Ehime Univ, Dept Gastroenterol & Metab, Toon, Japan. 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 2007 VL 46 IS 4 SU S MA 1393 BP 858A EP 858A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401656 ER PT J AU Kirkovsky, L Zhou, Y Norris, D Okamoto, E Nolan, TG Bartkowski, D Khandurina, J Sergeeva, M Murphy, D Ayida, B Xiang, A Ellis, D Blazel, J Sun, Z AF Kirkovsky, Leo Zhou, Yuefen Norris, Daniel Okamoto, Ellen Nolan, Thomas G. Bartkowski, Darian Khandurina, Julia Sergeeva, Maria Murphy, Douglas Ayida, Benjamin Xiang, Alan Ellis, David Blazel, Julie Sun, Zhongxiang TI ANA598, a novel non-nucleoside inhibitor of HCVNS5B polymerase, exhibits favorable pharmacokinetic properties in multiple preclinical species SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Ehime Univ, Dept Gastroenterol & Metab, Grad Sch Med, Toon, Japan. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 3 Z9 4 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 2007 VL 46 IS 4 SU S MA 1392 BP 858A EP 858A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401655 ER PT J AU Yazdanpanah, Y Vray, M Meynard, J Losina, E Weinstein, MC Morand-Joubert, L Goldie, SJ Hsu, HE Walensky, RP Dalban, C Sax, P Girard, P Freedberg, K AF Yazdanpanah, Y. Vray, M. Meynard, J. Losina, E. Weinstein, M. C. Morand-Joubert, L. Goldie, S. J. Hsu, H. E. Walensky, R. P. Dalban, C. Sax, Pe Girard, Pm Freedberg, Ka TI The long-term benefits of genotypic resistance testing in patients with extensive prior antiretroviral therapy: a model-based approach SO HIV MEDICINE LA English DT Article DE cost-effectiveness; costs; genotype testing; HIV infection; long-term effectiveness ID EXPERIENCED HIV-1-INFECTED PATIENTS; SOCIETY-USA PANEL; IMMUNODEFICIENCY-VIRUS TYPE-1; OPTIMIZED BACKGROUND REGIMEN; COST-EFFECTIVENESS ANALYSIS; DRUG-RESISTANCE; HIV DISEASE; OPPORTUNISTIC INFECTIONS; UPDATED RECOMMENDATIONS; VIROLOGICAL RESPONSE AB Objectives Resistance testing in HIV disease may provide long-term benefits that are not evident from short-term data. Our objectives were to estimate the long-term effectiveness, cost and cost-effectiveness of genotype testing in patients with extensive antiretroviral exposure. Methods We used an HIV simulation model to estimate the long-term effectiveness and cost-effectiveness of genotype testing. Clinical data incorporated into the model were from NARVAL, a randomized trial of resistance testing in patients with extensive antiretroviral exposure, and other randomized trials. Each simulated patient was eligible for up to three sequential regimens of antiretroviral therapy (i.e. two additional regimens beyond the trial-based regimen) using drugs not available at the time of the study, such as lopinavir/ritonavir, darunavir/ritonavir and enfuvirtide. Results In the long term, projected undiscounted life expectancy increased from 132.2 months with clinical judgement alone to 147.9 months with genotype testing. Median survival was estimated at 11.9 years in the resistance testing arm vs 10.4 years in the clinical judgement alone arm. Because of increased survival, the projected lifetime discounted cost of genotype testing was greater than for clinical judgement alone (is an element of 313 900 vs is an element of 263 100; US$399 000 vs US$334 400). Genotype testing cost is an element of 69 600 (US$88 500) per quality-adjusted life year gained compared with clinical judgement alone. Conclusions In patients with extensive prior antiretroviral exposure, genotype testing is likely to increase life expectancy in the long term as a result of the increased likelihood of receiving two active new drugs. Genotype testing is associated with cost-effectiveness comparable to that of strategies accepted in patients with advanced HIV disease, such as enfuvirtide use. C1 Ctr Hosp Tourcoing, Serv Univ Malad Infectieuses & Voyageur, Fac Med Lille, F-59208 Tourcoing, France. Fac Med Lille, EA 2694, F-59045 Lille, France. CNRS, URA 362, Lab Rech Econ & Sociales, Lille, France. Univ Paris 06, INSERM, EMI 0214, Paris, France. Ctr Hosp Univ St Antoine, Serv Univ Malad Infectieuses, Paris, France. Boston Univ, Sch Publ Hlth, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Ctr Hosp St Antoine, Serv Microbiol, Paris, France. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Yazdanpanah, Y (reprint author), Ctr Hosp Tourcoing, Serv Univ Malad Infectieuses & Voyageur, Fac Med Lille, 135 Rue President Coty,BP 619, F-59208 Tourcoing, France. EM yyazdan@yahoo.com OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [K23 AI001794, AI42006, K23 AI001794-05, K23 AI0794, K24 AI062476, K24 AI062476-01, K25 AI050436, K25 AI050436-05, K25 AI50436, P30 AI042851, P30 AI042851-05, P30 AI42851, R01 AI042006, R01 AI042006-07, R21 AI042006, R37 AI042006]; PHS HHS [U64/CCU 114927, U64/CCU 119525] NR 51 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-2662 J9 HIV MED JI HIV Med. PD OCT PY 2007 VL 8 IS 7 BP 439 EP 450 DI 10.1111/j.1468-1293.2007.00491.x PG 12 WC Infectious Diseases SC Infectious Diseases GA 203TO UT WOS:000248997100005 PM 17760736 ER PT J AU Auranen, T Nummenmaa, A Hamalainen, MS Jaaskelainen, IP Lampinen, J Vehtari, A Sams, M AF Auranen, Toni Nummenmaa, Aapo Hamalainen, Matti S. Jaaskelainen, Iiro P. Lampinen, Jouko Vehtari, Aki Sams, Mikko TI Bayesian inverse analysis of neuromagnetic data using cortically constrained multiple dipoles SO HUMAN BRAIN MAPPING LA English DT Article DE inverse problem; MEG; equivalent current dipoles; cortical constraints; Bayesian analysis; Monte Carlo ID REVERSIBLE JUMP; MEG INVERSE; HUMAN BRAIN; INFERENCE; EEG; MAGNETOENCEPHALOGRAPHY; RECONSTRUCTION; LOCALIZATION; PRIORS; MODEL AB A recently introduced Bayesian model for magnetoencephalographic (MEG) data consistently localized multiple simulated dipoles with the help of marginalization of spatiotemporal background noise covariance structure in the analysis [Jun et al., (2005): Neuroimage 28:84-98]. Here, we elaborated this model to include subject's individual brain surface reconstructions with cortical location and orientation constraints. To enable efficient Markov chain Monte Carlo sampling of the dipole locations, we adopted a parametrization of the source space surfaces with two continuous variables (i.e., spherical angle coordinates). Prior to analysis, we simplified the likelihood by exploiting only a small set of independent measurement combinations obtained by singular value decomposition of the gain matrix, which also makes the sampler significantly faster. We analyzed both realistically simulated and empirical MEG data recorded during simple auditory and visual stimulation. The results show that our model produces reasonable solutions and adequate data fits without much manual interaction. However, the rigid cortical constraints seemed to make the utilized scheme challenging as the sampler did not switch modes of the dipoles efficiently. This is problematic in the presence of evidently highly multimodal posterior distribution, and especially in the relative quantitative comparison of the different modes. To overcome the difficulties with the present model, we propose the use of loose orientation constraints and combined model of prelocalization utilizing the hierarchical minimum-norm estimate and multiple dipole sampling scheme. C1 Helsinki Univ Technol, Lab Computat Engn, FI-02015 Helsinki, Finland. Helsinki Univ Technol, Adv Magnet imaging Ctr, FIN-02150 Espoo, Finland. Massachusetts Gen Hosp, MIT, MGH HMS Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Helsinki Univ Technol, Brain Res Unit, Low Temp Lab, FIN-02150 Espoo, Finland. RP Auranen, T (reprint author), Helsinki Univ Technol, Lab Computat Engn, POB 9203, FI-02015 Helsinki, Finland. EM Toni.Auranen@hut.fi RI Jaaskelainen, Iiro/C-7392-2012; Sams, Mikko/G-7060-2012; Vehtari, Aki/A-7584-2008; Hamalainen, Matti/C-8507-2013; Lampinen, Jouko/D-3927-2014; Auranen, Toni/J-7137-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Vehtari, Aki/0000-0003-2164-9469; NR 42 TC 11 Z9 11 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD OCT PY 2007 VL 28 IS 10 BP 979 EP 994 DI 10.1002/hbm.20334 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 218BJ UT WOS:000249990700007 PM 17370346 ER PT J AU Mertz, KD Demichetis, F Kim, R Schraml, P Storz, M Diener, PA Moch, H Rubin, MA AF Mertz, Kirsten D. Demichetis, Francesca Kim, Robert Schraml, Peter Storz, Martina Diener, Pierre-Andre Moch, Holger Rubin, Mark A. TI Automated immunofluorescence analysis defines microvessel area as a prognostic parameter in clear cell renal cell cancer SO HUMAN PATHOLOGY LA English DT Article DE clear cell renal cell cancer; microvessel density (MVD); microvessel area (MVA); automated quantitative analysis (AQUA); prognosis ID TUMOR ANGIOGENESIS; QUANTITATIVE-ANALYSIS; TISSUE MICROARRAYS; BREAST-CANCER; CARCINOMA; DENSITY; EXPRESSION; METASTASIS; PROLIFERATION; GENES AB Microvessel density (MVD) has been reported to have prognostic relevance for clear cell renal cell carcinoma (ccRCC). However, this finding is controversial because of the difficulty of MVD evaluation in this complex vascularized tumor type. The present study evaluates the use of an automated quantitative analysis (AQUA) system for objective and reproducible determination of tumor vascularization in clear cell renal cell carcinoma (ccRCC). The AQUA system was applied to tissue microarrays with 284 primary ccRCC tumors. To determine angiogenesis in ccRCC, we created an epithelial/stromal mask consisting of CD10, epithelial membrane antigen, and vimentin to distinguish epithelial tumor cells from CD34-positive endothelial cells. Using immuno fluorescence and computeraided quantification of CD34 expression, we measured the relative microvessel area (MVA) and compared the MVA to the manually counted MVD. The MVA determined by AQUA in a test set with 209 ccRCCs ranged from 0% to 30.3% (mean +/- SD, 10.1% +/- 6.3%). The manually determined MVD ranged from 6 to 987 vessels/mm(2) (416.8 +/- 252.8 vessels/mm(2)). MVA and MVD were significantly correlated (P <.001). A larger MVA was associated with histologic grade (P <.001), tumor stage (P =.008), presence of metastasis (P =.005), presence of sarcomatoid areas (P <.001), and tumor-specific survival (P <.001). Using MVA as defined in the test set, all associations with clinical and pathologic parameters were confirmed in a second independent validation set. MVA determination by AQUA is an objective and reliable method to quantify tumor vascularization in ccRCC. A large MVA correlates with a high MVD and is associated with better patient prognosis. (c) 2007 Published by Elsevier Inc. C1 Univ Zurich Hosp, Inst t Surg Pathol, CH-8091 Zurich, Switzerland. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Ctr, Boston, MA 02115 USA. Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. Hosp St Gallen, Inst Pathol, St Gallen, Switzerland. RP Rubin, MA (reprint author), Univ Zurich Hosp, Inst t Surg Pathol, 75 Francis St, CH-8091 Zurich, Switzerland. EM holger.moch@usz.ch; marubin@partners.org OI Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 FU NCI NIH HHS [NCI P50 CA090381] NR 30 TC 29 Z9 31 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 2007 VL 38 IS 10 BP 1454 EP 1462 DI 10.1016/j.humpath.2007.05.017 PG 9 WC Pathology SC Pathology GA 216WJ UT WOS:000249909400003 PM 17889675 ER PT J AU Dai, QY Xu, MD Yao, M Sun, BG AF Dai, Qiuyan Xu, Mengdan Yao, Min Sun, Baogui TI The anti-inflammatory effects of AT1 receptor antagonists in spontaneously hypertensive rats SO HYPERTENSION LA English DT Meeting Abstract CT 61st Annual High Blood Pressure Reseach Conference CY SEP 26-29, 2007 CL Tucson, AZ C1 Jiao Tong Univ, Shanghai First Peoples Hosp, Shanghai 200030, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2007 VL 50 IS 4 BP E124 EP E124 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 212HN UT WOS:000249586900396 ER PT J AU Wherry, EJ Ha, SJ Kaech, SM Haining, WN Sarkar, S Kalia, V Subramaniam, S Blattman, JN Barber, DL Ahmed, R AF Wherry, E. John Ha, Sang-Jun Kaech, Susan M. Haining, W. Nicholas Sarkar, Surojit Kalia, Vandana Subramaniam, Shruti Blattman, Joseph N. Barber, Daniel L. Ahmed, Rafi TI Molecular signature of CD8(+) T cell exhaustion during chronic viral infection SO IMMUNITY LA English DT Article ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; TRANSCRIPTIONAL REPRESSOR BLIMP-1; INHIBITORY RECEPTOR; PD-1 EXPRESSION; NK CELLS; MEMORY; ACTIVATION; PERSISTENCE; EFFECTOR; DIFFERENTIATION AB Chronic viral infections often result in T cell exhaustion. To determine the molecular signature of exhaustion, we compared the gene-expression profiles of dysfunctional lymphocytic choriomeningitis virus (LCMV)-specific CD8(+) T cells from chronic infection to functional LCMV-specific effector and memory CD8(+) T cells generated after acute infection. These data showed that exhausted CD8+ T cells: (1) overexpressed several inhibitory receptors, including PD-1, (2) had major changes in T cell receptor and cytokine signaling pathways, (3) displayed altered expression of genes involved in chemotaxis, adhesion, and migration, (4) expressed a distinct set of transcription factors, and (5) had profound metabolic and bioenergetic deficiencies. T cell exhaustion was progressive, and gene-expression profiling indicated that T cell exhaustion and anergy were distinct processes. Thus, functional exhaustion is probably due to both active suppression and passive defects in signaling and metabolism. These results provide a framework for designing rational immunotherapies during chronic infections. C1 Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. RP Wherry, EJ (reprint author), Wistar Inst Anat & Biol, Program Immunol, 3601 Spruce St,Room 251, Philadelphia, PA 19104 USA. EM jwherry@wistar.org; ra@microbio.emory.edu OI Ha, Sang-Jun/0000-0002-1192-6031 FU NIAID NIH HHS [AI071309, AI30048] NR 56 TC 662 Z9 673 U1 2 U2 26 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2007 VL 27 IS 4 BP 670 EP 684 DI 10.1016/j.immuni.2007.09.006 PG 15 WC Immunology SC Immunology GA 225AY UT WOS:000250490700017 PM 17950003 ER PT J AU Roozendaal, R Carroll, MC AF Roozendaal, Ramon Carroll, Michael C. TI Complement receptors CD21 and CD35 in humoral immunity SO IMMUNOLOGICAL REVIEWS LA English DT Review DE antigen trafficking; follicular dendritic cells; germinal center; B-cell memory ID FOLLICULAR DENDRITIC CELLS; HERPES-SIMPLEX-VIRUS; DECAY-ACCELERATING FACTOR; ZONE B-CELLS; LYMPH-NODE; ANTIBODY-RESPONSES; INNATE IMMUNITY; MARGINAL ZONE; SUBCAPSULAR SINUS; GERMINAL-CENTERS AB The complement system is a family of proteins that is involved in both innate and adaptive immunity. Complement receptors CD21 and CD35, which recognize activated products of C3 and C4, are predominantly expressed on B cells and follicular dendritic cells (FDCs) in the mouse. In this review, we focus on the role of FDC-expressed CD21 and CD35 in humoral immunity. They are the principle receptors for uptake and retention of immune complexes. In their absence, memory B-cell survival is markedly impaired. This is likely because of the lack of antigen but could also reflect a role for complement C3d ligand. How antigen is transported to FDCs remains an open question. In recent unpublished work using multiphoton intravital imaging, we found that small protein antigens presented in the lymph drain rapidly into B-cell follicles and are taken up by FDCs in a complement-dependent manner. C1 Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Mol Cell Biol & Immunol, Van Boechorstr 7, NL-1081 BT Amsterdam, Netherlands. EM carroll@cbr.med.harvard.edu NR 66 TC 79 Z9 84 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 2007 VL 219 BP 157 EP 166 DI 10.1111/j.1600-065X.2007.00556.x PG 10 WC Immunology SC Immunology GA 210AQ UT WOS:000249429500012 PM 17850488 ER PT J AU Perencevich, EN Stone, PW Wright, SB Carmeli, Y Fisman, DN Cosgrove, SE AF Perencevich, Eli N. Stone, Patricia W. Wright, Sharon B. Carmeli, Yehuda Fisman, David N. Cosgrove, Sara E. TI Raising standards while watching the bottom line: Making a business case for infection control SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID SURGICAL-SITE INFECTIONS; RESISTANT STAPHYLOCOCCUS-AUREUS; VENTILATOR-ASSOCIATED PNEUMONIA; CLUSTER-RANDOMIZED TRIALS; ARTERY-BYPASS-SURGERY; CARE-ASSOCIATED INFECTIONS; BLOOD-STREAM INFECTIONS; CRITICALLY-ILL PATIENTS; CHRONIC DISEASE SCORE; ANTIMICROBIAL RESISTANCE AB While society would benefit from a reduced incidence of nosocomial infections, there is currently no direct reimbursement to hospitals for the purpose of infection control, which forces healthcare institutions to make economic decisions about funding infection control activities. Demonstrating value to administrators is an increasingly important function of the hospital epidemiologist because healthcare executives are faced with many demands and shrinking budgets. Aware of the difficulties that face local infection control programs, the Society for Healthcare Epidemiology of America ( SHEA) Board of Directors appointed a task force to draft this evidence-based guideline to assist hospital epidemiologists in justifying and expanding their programs. In Part 1, we describe the basic steps needed to complete a business-case analysis for an individual institution. A case study based on a representative infection control intervention is provided. In Part 2, we review important basic economic concepts and describe approaches that can be used to assess the financial impact of infection prevention, surveillance, and control interventions, as well as the attributable costs of specific healthcare-associated infections. Both parts of the guideline aim to provide the hospital epidemiologist, infection control professional, administrator, and researcher with the tools necessary to complete a thorough business-case analysis and to undertake an outcome study of a nosocomial infection or an infection control intervention. C1 Univ Maryland Sch Med, John Hopkins Med Inst, Dept Epidemiol & Prevent Med, Div Infect Dis & Antibiot Management Prog, Baltimore, MD USA. Columbia Univ, Sch Nursing, New York, NY 10027 USA. Beth Israel Deacones Med Ctr, Div Infect Dis, Boston, MA USA. Tel Aviv Sourasky Med Ctr, Div Infect Dis Epidemiol, Tel Aviv, Israel. Univ Toronto, Res Inst Hosp Sick Children, Ontario Public Hlth Lab Branch, Child Hlth Evaluat Sci Prog, Toronto, ON, Canada. RP Perencevich, EN (reprint author), Univ Maryland, Sch Med, Univ Maryland Med Ctr, Associate Hosp Epidermiol,Dept Epidemiol & Prev M, 100 N Greene St,Lower Level, Baltimore, MD 21201 USA. EM eperence@epi.umaryland.edu NR 98 TC 88 Z9 88 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 2007 VL 28 IS 10 BP 1121 EP 1133 DI 10.1086/521852 PG 13 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 222OM UT WOS:000250306800001 PM 17933084 ER PT J AU Weintraub, D Xie, S Karlawish, J Siderowf, A AF Weintraub, Daniel Xie, Sharon Karlawish, Jason Siderowf, Andrew TI Differences in depression symptoms in patients with Alzheimer's and Parkinson's diseases: evidence from the 15-item Geriatric Depression Scale (GDS-15) SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE rating scale; depression; Alzheimer's disease; Parkinson's disease; geriatric depression scale ID PROVISIONAL DIAGNOSTIC-CRITERIA; RATING-SCALE; WORK GROUP; DEMENTIA; POPULATION; COMMUNITY; VALIDITY AB Objective Depression occurs frequently inpatients with both Alzheimer's disease (AD) and Parkinson's disease (PD), but there has been little comparison of depression symptoms in the two populations. Method The 15-item Geriatric Depression Scale (GDS-15) was administered as a depression screening instrument to 232 AD patients and 266 PD specialty care patients with at most mild dementia. Logistic regression models were used to determine disease-specific associations with individual GDS-15 items, and factor analysis was used to assess GDS-15 factor structure in the two populations. Results Controlling for total GDS-15 score and other covariates, AD patients reported more dissatisfaction with life (p=0.03) and memory problems (p<0.001), while PD patients reported more fearfulness (p=0.01), helplessness (p < 0.01), a preference to stay at home (p = 0.02), and diminished energy (p < 0.01). Three factors were generated in PD (explaining 55% of the total variance) and five in AD (explaining 59% of the total variance), and the two main factors generated in both populations related primarily to unhappiness and negative thoughts. Conclusions The factor structure of the GDS-15 is similar in AD and PD patients with at most mild stage dementia, but between-group differences on 6 of the GDS-15 items suggests the non-specificity of certain items in the two populations. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Alzheimers Dis Ctr, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, PADRECC, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3535 Market St,Room 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIA NIH HHS [P30-AG10124, P30 AG010124]; NIMH NIH HHS [K23 MH067894-04, K23 MH067894]; PHS HHS [K23-067894] NR 23 TC 8 Z9 8 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD OCT PY 2007 VL 22 IS 10 BP 1025 EP 1030 DI 10.1002/gps.1785 PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 221OS UT WOS:000250237800015 PM 17562521 ER PT J AU Oliva, E Garcia-Miralles, N Vu, Q Young, RH AF Oliva, Esther Garcia-Miralles, Noemi Vu, Quynh Young, Robert H. TI CD10 expression in pure stromal and sex cord-stromal tumors of the ovary: An immunohistochemical analysis of 101 cases SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Review DE CD10; sex cord; stromal tumors; steroid cell tumors; ovary; differential diagnosis; immunohistochemistry ID NEUTRAL ENDOPEPTIDASE 24.11; CLEAR-CELL CARCINOMA; GONADOTROPIN-RELEASING-HORMONE; MULLERIAN-INHIBITING SUBSTANCE; LEUKEMIA ANTIGEN CALLA; HUMAN PROSTATE-CANCER; SMOOTH-MUSCLE TUMORS; MONOCLONAL-ANTIBODY; GRANULOSA-CELL; DIFFERENTIAL-DIAGNOSIS AB CD 10 has been recently advocated as a good immunohistochemical marker for endometrial stromal tumors. Metastatic endometrial stromal tumors to the ovary and primary endometrioid stromal sarcomas may show overlapping histological features with pure stromal and sex cord-stromal tumors (SCSTs). We investigated CD10 expression in a large series of pure stromal and SCSTs of the ovary to ascertain whether CD 10 may aid in this differential diagnosis. Archival material from 11 fibromas, 10 thecomas, 10 sclerosing stromal tumors (SSTs), 10 adult granulosa cell tumors (AGCTs), 4 luteinized AGCTs, 9 juvenile granulosa cell tumors (JGCTs), 9 Sertoli cell tumors, 9 Sertoli-Leydig cell tumors, 11 sex cord tumors with annular tubules, 10 steroid cell tumors (StCTs), and 8 fibrosarcomas of the ovary were immunostained for CD10. The percentage of cells stained (< 5%, 5%-39%, 40%-75%, and > 75%) and intensity of staining (1+, 2+, 3+) were evaluated. CD10 was expressed in 7 of 10 thecomas (4 with 5%-75% and mostly 1+), 9 of 10 SSTs (7 with 5%-39% + cells, mostly 1+), 9 of 10 AGCTs (< 5%-39%, four 1+, five 2+), 1 of 4 luteinized AGCTs (< 5% and 1+), 8 of 9 JGCTs (mostly < 5% to 39% and +1), 4 of 9 Sertoli cell tumors (either focal or > 75% with variable intensity), 4 of 9 Sertoli-Leydig cell tumors (mostly < 10% with variable staining), with the Leydig cells being positive in only 1 tumor (1+ and < 5%), and 7 of 10 StCTs (4 tumors with more than 75% + cells, from 1+ to 3+). All fibromas, all but 1 fibrosarcoma (< 5% and 1+), and all sex cord tumors with annular tubules were CD10 negative. CD10 expression was frequently seen in StCTs, SSTs, and thecomas of the ovary, although the latter 2 categories usually showed only faint immunoreactivity. In conclusion the frequency and intensity of CD10 immunoreactivity in pure stromal and sex cord-stromal ovarian tumors are low and contrast with the typical strong and diffuse immunostaining seen in endometrial stromal tumors; however, faint CD10 positivity is consistent with the diagnosis of ovarian SCST. Steroid cell tumors are often positive for CD10, but these tumors do not pose problems in differential diagnosis with endometrial stromal tumors. CD10 may play a useful role in aiding the differential between endometrial stromal tumors in the ovary and SCST and stromal tumors. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 2, Boston, MA 02114 USA. EM eoliva@partners.org NR 121 TC 25 Z9 29 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 2007 VL 26 IS 4 BP 359 EP 367 DI 10.1097/pgp.0b013e318064511c PG 9 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 213KV UT WOS:000249666700001 PM 17885484 ER PT J AU Trofimov, A Nguyen, PL Coen, JJ Doppke, KP Schneider, RJ Adams, JA Bortfeld, TR Zietman, AL DeLaney, TF Shipley, WU AF Trofimov, Alexei Nguyen, Paul L. Coen, John J. Doppke, Karen P. Schneider, Robert J. Adams, Judith A. Bortfeld, Thomas R. Zietman, Anthony L. DeLaney, Thomas F. Shipley, William U. TI Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: A treatment planning comparison SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; comparative treatment planning; intensity-modulated radiotherapy; 3D-conformal proton therapy; intensity-modulated proton therapy ID DOSE-VOLUME HISTOGRAMS; MODULATED RADIATION-THERAPY; CONFORMAL RADIOTHERAPY; 2ND CANCERS; CARCINOMA; IRRADIATION; RISK; IMMOBILIZATION; EXPERIENCE; TOXICITY AB Purpose: To compare intensity-modulated photon radiotherapy (IMRT) with three-dimensional conformal proton therapy (3D-CPT) for early-stage prostate cancer, and explore the potential utility of intensity-modulated proton therapy (IMPT). Methods and Materials: Ten patients were planned with both 3D-CPT (two parallel-opposed lateral fields) and IMRT (seven equally spaced coplanar fields). Prescribed dose was 79.2 Gy (or cobalt Gray-equivalent, [CGE] for protons) to the prostate gland. Dose-volume histograms, dose conformity, and equivalent uniform dose (EUD) were compared. Additionally, plans were optimized for 3D-CPT with nonstandard beam configuration, and for IMPT assuming delivery with beam scanning. Results: At least 98% of the planning target volume received the prescription dose. IMRT plans yielded better dose conformity to the target, whereas proton plans achieved higher dose homogeneity and better sparing of rectum and bladder in the range below 30 Gy/CGE. Bladder volumes receiving more than 70 Gy/CGE (V-70) were reduced, on average, by 34% with IMRT vs. 3D-CPT, whereas rectal V-70 were equivalent. EUD from 3D-CPT and IMRT plans were indistinguishable within uncertainties for both bladder and rectum. With the use of small-angle lateral-oblique fields in 3D-CPT and IMPT, the rectal V-70 was reduced by up to 35% compared with the standard lateral configuration, whereas the bladder V-70 increased by less than 10%. Conclusions: In the range higher than 60 Gy/CGE, IMRT achieved significantly better sparing of the bladder, whereas rectal sparing was similar with 3D-CPT and IMRT. Dose to healthy tissues in the range lower than 50% of the target prescription was substantially lower with proton therapy. (c) 2007 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Trofimov, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM atrofimov@partners.org OI Schneider, Robert/0000-0001-5807-5564 FU NCI NIH HHS [5P01-CA21239-25, P01 CA021239, P01 CA021239-27, P01 CA021239-28, P01 CA021239-29A1] NR 40 TC 96 Z9 96 U1 2 U2 7 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 2007 VL 69 IS 2 BP 444 EP 453 DI 10.1016/j.ijrobp.2007.03.018 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 215GK UT WOS:000249796100018 PM 17513063 ER PT J AU Grosu, AL Souvatzoglou, M Roper, B Dobritz, M Wiedenmann, N Jacob, V Wester, HJ Reischl, G Machulla, HJ Schwaiger, M Molls, M Piert, M AF Grosu, Anca-Ligia Souvatzoglou, Michael Roeper, Barbara Dobritz, Martin Wiedenmann, Nicole Jacob, Vesna Wester, Hans-Juergen Reischl, Gerald Machulla, Hans-Juergen Schwaiger, Markus Molls, Michael Piert, Morand TI Hypoxia imaging with FAZA-PET and theoretical considerations with regard to dose painting for individualization of radiotherapy in patients with head and neck cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE hypoxia; FAZA-PET; dose painting; IMRT; head-and-neck tumors ID POSITRON-EMISSION-TOMOGRAPHY; F-18 FLUOROMISONIDAZOLE; TUMOR HYPOXIA; RADIATION ONCOLOGY; F-18-FLUOROMISONIDAZOLE PET; TISSUE OXYGENATION; LUNG-CANCER; TIRAPAZAMINE; ARABINOSIDE; CHEMORADIATION AB Purpose: To evaluate the role of hypoxia positron emission tomography (PET) using [F-18]fluoroazomycin-arabinoside (FAZA) in head and neck cancer for radiation treatment planning using intensity-modulated radiotherapy and dose painting. Methods and Materials: Eighteen patients with advanced squamous cell head and neck cancer were included. Both FAZA-PET and axial CT were performed using mask fixation. The data were coregistered using software based on mutual information. Contours of tumor (primary gross tumor volume, GTV/CT-P) and lymph node metastases (GTV/CT-N) were outlined manually, and FAZA standardized uptake values (SUVs) were calculated automatically. The hypoxic subvolume (GTV/PET-FAZA) having at least 50% more FAZA uptake than background (mean SUV) neck muscle tissue was contoured automatically within GTV/CT-P (GTV/PET-FAZA-P) and GTV/CT-N (GTV/PET-FAZA-N). Results: The median GTV/PET-FAZA-P was 4.6 mL, representing 10.8% (range, 0.7-52%) of the GTV/CT-P The GTV/PET-FAZA-P failed to correlate significantly with the GTV/CT-P (p = 0.06). The median GTV/PET-FAZA-N was 4.1 mL, representing 8.3% (range, 2.2-51.3%) of the GTV/CT-N. It was significantly correlated with the GTV/PET-N (p = 0.006). The GTV/PET-FAZA-P was located in a single confluent area in 11 of 18 patients (61 %) and was diffusely dispersed in the whole GTV/CT-P in 4 of 18 patients (22%), whereas no hypoxic areas were identified in 3 of 18 patients (17%). The GTV/PET-FAZA-N was outlined as a single confluent region in 7 of 18 patients (39%), in multiple diffuse hypoxic regions in 4 of 18 patients (22%), and was not delineated in 7 of 18 patients (39%). Conclusion: This study demonstrates that FAZA-PET imaging could be used for a hypoxia-directed intensity-modulated radiotherapy approach in head and neck cancer. (c) 2007 Elsevier Inc. C1 Tech Univ Munich, Klinikum Rechts Isar, Dept Radiat Oncol, D-8000 Munich, Germany. Tech Univ Munich, Klinikum Rechts Isar, Dept Nucl Med, D-8000 Munich, Germany. Tech Univ Munich, Klinikum Rechts Isar, Inst Radiol, D-8000 Munich, Germany. Univ Tubingen, Sect Radiopharm, Tubingen, Germany. Univ Texas, MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. Univ Michigan, Div Nucl Med, Dept Radiol, Ann Arbor, MI 48109 USA. RP Grosu, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Francis H Burr Proton Therapy C, 30 Fruit St, Boston, MA 02114 USA. EM agrosu@partners.org OI schwaiger, markus /0000-0002-2305-7144 NR 53 TC 137 Z9 141 U1 2 U2 7 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 2007 VL 69 IS 2 BP 541 EP 551 DI 10.1016/j.ijrobp.2007.05.079 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 215GK UT WOS:000249796100031 PM 17869667 ER PT J AU Court, LE Tishler, RB AF Court, Laurence E. Tishler, Roy B. TI Experimental evaluation of the impact of different headand-neck intensity-modulated radiation therapy planning techniques on doses to the skin and shallow targets SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE skin toxicity; head and neck cancer; intensity-modulated radiation therapy; PTV ID RADIOTHERAPY; MARGINS; SURFACE; IMRT; PROBABILITY; ERRORS; TUMORS AB Purpose: To investigate experimentally the impact of different head-and-neck intensity-modulated radiation therapy (IMRT) planning techniques on doses to the skin and shallow targets. Methods and Materials: A semicylindrical phantom was constructed with micro-MOSFET dosimeters (Thomson-Nielson, Ottawa, Ontario, Canada) at 0-, 3-, 6-, 9-, and 12-mm depths. The planning target volume (PTV) was pulled back 0, 3, or 5 mm from the body contour. The IMRT plans were created to maximize PTV coverage, with one of the following strategies: (a) aim for a maximum 110% hotspot, with 115% allowed; (b) aims for a maximum 105% hotspot; (c) aims for a maximum 105% hotspot and 50% of skin to get a maximum 70% of the prescribed dose; and (d) aim for 99% of the PTV volume to receive 90-93% of prescribed dose, with a maximum 105% hotspot, and with the dose to the skin structure minimized. Doses delivered using a linear accelerator were measured. Setup uncertainty was simulated by intentionally shifting the phantom in a range of 8 mm, and calculating the delivered dose for a range of systematic and random uncertainties. Results: From lowest to highest skin dose, the planning strategies were in the order of c, d, b, and a, but c showed a tendency to underdose tissues at depth. Delivered doses varied by 10-20%, depending on planning strategy. For typical setup uncertainties, cumulative dose reduction to a point 6 mm deep was <4%. Conclusions: It is useful to use skin as a sensitive structure, but a minimum dose constraint must be used for the PTV if unwanted reductions in dose to nodes near the body surface are to be avoided. Setup uncertainties are unlikely to give excessive reductions in cumulative dose. (c) 2007 Elsevier Inc. C1 Dana Farber & Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Court, LE (reprint author), Dana Farber & Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM lcourt@Iroc.harvard.edu NR 17 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2007 VL 69 IS 2 BP 607 EP 613 DI 10.1016/j.ijrobp.2007.03.004 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 215GK UT WOS:000249796100038 PM 17869674 ER PT J AU Kawahara, S Hata, Y Miura, M Kita, T Sengoku, A Nakao, S Mochizuki, Y Enaida, H Ueno, A Hafezi-Moghadam, A Ishibashi, T AF Kawahara, Shuhei Hata, Yasuaki Miura, Muneki Kita, Takeshi Sengoku, Akihito Nakao, Shintaro Mochizuki, Yasutaka Enaida, Hiroshi Ueno, Akifumi Hafezi-Moghadam, Ali Ishibashi, Tatsuro TI Intracellular events in retinal glial cells exposed to ICG and BBG SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INTERNAL LIMITING MEMBRANE; PIGMENT EPITHELIAL-CELLS; MACULAR HOLE SURGERY; BRILLIANT BLUE-G; INDOCYANINE GREEN; TRYPAN BLUE; P2X(7) RECEPTORS; PROLIFERATIVE VITREORETINOPATHY; SUBRETINAL INJECTION; EPIRETINAL MEMBRANE AB PURPOSE. To investigate the intracellular events in retinal glial cells exposed to indocyanine green (ICG) and brilliant blue G (BBG). METHODS. The human Muller cell line MIO-M1 was exposed to a low dose (0.25 mg/mL) and a clinical dose (2.5 mg/mL) of ICG and a clinical dose (0.25 mg/mL) of BBG for 15 minutes, respectively. To quantify the proliferation and viability of the cells, [H-3]-thymidine incorporation was measured and cell numbers were counted 24 hours after treatment. Cell morphology was evaluated using phase-contrast microscopy and transmission electron microscopy. The effects of ICG and BBG on phosphorylation of p38 MAPK and cleavage of caspase-9 and caspase-3 were examined by Western blot. RESULTS. ICG and BBG significantly reduced [H-3]-thymidine incorporation in MIO-M1 cells compared with the vehicle-treated controls (P < 0.01). Cell number significantly decreased after exposure to ICG at 2.5 or 0.25 mg/mL (P < 0.01) but did not decrease after exposure to BBG at 0.25 mg/mL. Transmission electron microscopy revealed apoptotic changes only in the ICG-treated cells. Prominent p38 MAPK phosphorylation was observed in the presence of ICG, even at the low concentration and within a short time exposure; however, no apparent enhancement was observed in the presence of 0.25 mg/mL BBG. Furthermore, ICG, but not BBG, induced the cleavage of caspase-9 and caspase-3, which was inhibited by an inhibitor of p38 MAPK. CONCLUSIONS. ICG is toxic to retinal glial cells because it induces apoptosis, involving induction of the caspase cascade through p38 MAPK phosphorylation. In contrast, BBG does not cause apoptosis and thus could be a safer adjuvant during vitreoretinal surgery. C1 Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. RP Hata, Y (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM hatachan@med.kyushu-u.ac.jp OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 NR 55 TC 38 Z9 43 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 2007 VL 48 IS 10 BP 4426 EP 4432 DI 10.1167/iovs.07-0358 PG 7 WC Ophthalmology SC Ophthalmology GA 214SE UT WOS:000249757600008 PM 17898261 ER PT J AU Blalock, TD Spurr-Michaud, SJ Tisdale, AS Heimer, SR Gilmore, MS Ramesh, V Gipson, IK AF Blalock, Timothy D. Spurr-Michaud, Sandra J. Tisdale, Ann S. Heimer, Susan R. Gilmore, Michael S. Ramesh, Vijaya Gipson, Ilene K. TI Functions of MUC16 in corneal epithelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MEMBRANE-ASSOCIATED MUCINS; FEMALE REPRODUCTIVE-TRACT; OVARIAN-CANCER ANTIGEN; OCULAR SURFACE; PSEUDOMONAS-AERUGINOSA; ERM PROTEINS; STAPHYLOCOCCUS-AUREUS; CARBOHYDRATE EPITOPE; TERMINAL DOMAIN; ROSE-BENGAL AB PURPOSE. The membrane-associated mucin MUC16, a heavily O-glycosylated transmembrane protein, is expressed by the ocular surface epithelia and localized on the tips of the surface microplicae. Although its functions in the ocular surface glycocalyx are unknown, it is thought that MUC16 provides a disadhesive barrier to the epithelial membrane. Two other membrane-associated mucins expressed by ocular surface epithelia, MUC1 and MUC4, are multifunctional and have signaling capabilities through their cytoplasmic tails and EGF-like domains, respectively. The MUC16 cytoplasmic tail has not been characterized, but, because it contains a polybasic amino acid sequence, it potentially interacts with the actin cytoskeleton through ezrin/radixin/moesin (ERM) actin-binding proteins. METHODS. The interaction of MUC16 with the actin cytoskeleton through ERMs was investigated using cytoplasmic tail peptides and ERM pull-down experiments. MUC16 functions were determined using RNA interference in immortalized human corneal-limbal epithelial (HCLE) cells. The effect of MUC16 knockdown on microplicae structure in HCLE cells was determined using scanning and immunoelectron microscopy. HCLE cells were incubated with rose bengal dye to measure the role of MUC16 in ocular surface barrier function. Binding of fluorescently labeled Staphylococcus aureus to HCLE cells was measured to determine the role of MUC16 in the protection of pathogen adherence on the ocular surface epithelium. RESULTS. MUC16 cytoplasmic tail peptides bound the N-terminus of ERMs, with no detectable binding of MUC1 and MUC4 peptides. No effect on surface membrane projections could be detected in HCLE cells after MUC16 suppression; however, HCLE cells incubated with rose bengal showed that exclusion of the dye was significantly reduced in cells with MUC16 suppression. In addition, S. aureus binding to HCLE cells was significantly increased with MUC16 suppression. CONCLUSIONS. These results suggest that MUC16 is a multifunctional molecule linked to the actin cytoskeleton. The expression of MUC16 in the ocular surface glycocalyx helps provide a disadhesive protective barrier for the epithelial surface. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RP Gipson, IK (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM ilene.gipson@schepens.harvard.edu FU NEI NIH HHS [R01 EY03306] NR 53 TC 96 Z9 97 U1 0 U2 8 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 2007 VL 48 IS 10 BP 4509 EP 4518 DI 10.1167/iovs.07-0430 PG 10 WC Ophthalmology SC Ophthalmology GA 214SE UT WOS:000249757600019 PM 17898272 ER PT J AU Wester, ST Rizzo, JF Balkwill, MD Wall, C AF Wester, Sara T. Rizzo, Joseph F., III Balkwill, M. David Wall, Conrad TI Optokinetic nystagmus as a measure of visual function in severely visually impaired patients SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EYE-MOVEMENTS; ACUITY; DEGENERATION; STIMULATION; VISION; RETINA; CELLS; FIELD AB PURPOSE. To evaluate the efficacy of using optokinetic nystagmus (OKN) as an objective measurement of vision in severely visually impaired patients, in whom it is difficult to measure visual function reliably. Objective visual acuity (VA) measurements would be useful in the pre- and postoperative assessment of severely visually impaired patients who are potential candidates for visual rehabilitation strategies, such as retinal prostheses, neural and stem cell transplantation, and molecular approaches. METHODS. Full-field visual stimuli were used to evoke horizontal OKN responses in 17 subjects. Eye movements were recorded and analyzed to determine the maximum stimulus velocity (V-max) at which subjects could maintain an OKN response. This endpoint was compared to logMAR VA and Goldmann visual field (VF) test results. RESULTS. V-max was dependent on VA, VF, and the spatial frequency ( SF) of the stimulus, yielding the equation V-max = 14.2 center dot log(VA) - 6.20 center dot log( SF) + 0.22 center dot VF + 25.0. The findings suggest that Vmax in the presence of full-field OKN stimuli may provide an objective measure of VA and peripheral vision. CONCLUSIONS. OKN testing may be useful as an additional, more objective means of assessing visual function in a select group of severely visually impaired patients who are being considered as candidates for new visual rehabilitative strategies. C1 Bascom Palmer Eye Inst, Miami, FL 33136 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Wester, ST (reprint author), Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA. EM swester2@med.miami.edu NR 32 TC 10 Z9 10 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2007 VL 48 IS 10 BP 4542 EP 4548 DI 10.1167/iovs.06-1206 PG 7 WC Ophthalmology SC Ophthalmology GA 214SE UT WOS:000249757600023 PM 17898276 ER PT J AU Poulaki, V Mitsiades, CS Kotoula, V Negri, J McMillin, D Miller, JW Mitsiades, N AF Poulaki, Vassiliki Mitsiades, Constantine S. Kotoula, Vassiliki Negri, Joseph McMillin, Douglas Miller, Joan W. Mitsiades, Nicholas TI The proteasome inhibitor bortezomib induces apoptosis in human retinoblastoma cell lines in vitro SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MULTIPLE-MYELOMA CELLS; ACTIVATING TRANSCRIPTION FACTOR-3; ENDOPLASMIC-RETICULUM STRESS; OVERCOMES DRUG-RESISTANCE; PHASE-II TRIAL; THERAPEUTIC APPLICATIONS; PROTEIN-DEGRADATION; PEDIATRIC-PATIENTS; SODIUM-BUTYRATE; REPRESSOR ATF3 AB novel class of antitumor agents, for the treatment of retinoblastoma. The proteasome inhibitor bortezomib (PS-341, Velcade; Millennium Pharmaceuticals, Cambridge, MA), approved by the US Food and Drug Administration for the treatment of multiple myeloma, is being studied for the treatment of several other malignancies. Among other effects, it inactivates the transcription factor nuclear factor-kappa B (NF-kappa B) by blocking the degradation of its inhibitor, I kappa B. NF-kappa B, which is constitutively active in human retinoblastoma cells and promotes their survival, represents a therapeutic target for patients with this malignancy. METHODS. The authors evaluated the effect of bortezomib on the retinoblastoma cell lines Y79 and WERI-Rb1 in vitro using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry with propidium iodide, gene expression profiling, RT-PCR, and immunoblotting. RESULTS. Bortezomib induced caspase-dependent apoptosis in both retinoblastoma cell lines at clinically achievable concentrations. Bortezomib upregulated heat-shock proteins, other stress-response proteins, proapoptotic molecules, cell-cycle regulators, transcription factors, cytokines, and several proteasome subunits and solute carrier proteins, whereas it down-regulated antiapoptotic and adhesion molecules. Bortezomib also induced cleavage of caspases, Bid and poly(ADP-ribose) polymerase ( PARP), and sensitized retinoblastoma cells to doxorubicin. CONCLUSIONS. Bortezomib induces a stress response and triggers caspase-dependent apoptosis in human retinoblastoma cells at clinically achievable concentrations. This study provides insight into the molecular mechanism(s) of the antitumor activity of bortezomib and a basis for future preclinical studies leading to clinical trials of bortezomib, alone or in combination with conventional chemotherapy, to improve patient outcomes in retinoblastoma. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Laser Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Aristotle Univ Thessaloniki, Sch Med, Dept Pathol, Thessaloniki, Greece. RP Poulaki, V (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Laser Lab, 243 Charles St, Boston, MA 02114 USA. EM poulakiv@hotmail.com NR 52 TC 21 Z9 21 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 2007 VL 48 IS 10 BP 4706 EP 4719 DI 10.1167/iovs.06-1147 PG 14 WC Ophthalmology SC Ophthalmology GA 214SE UT WOS:000249757600042 PM 17898295 ER PT J AU Matsubara, A Nakazawa, T Noda, K She, HC Connolly, E Young, TA Ogura, Y Gragoudas, ES Miller, JW AF Matsubara, Akihisa Nakazawa, Toru Noda, Kosuke She, Haicheng Connolly, Edward Young, Tara A. Ogura, Yuichiro Gragoudas, Evangelos S. Miller, Joan W. TI Photodynamic therapy induces caspase-dependent apoptosis in rat CNV model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; INTRAVITREAL TRIAMCINOLONE; SIGNAL-TRANSDUCTION; CELL APOPTOSIS; CYTOCHROME-C; ACTIVATION; VERTEPORFIN; PATHWAY AB PURPOSE. To investigate the mechanism of cell death in laser-induced choroidal neovascularization (CNV) after photodynamic therapy (PDT). METHODS. PDT was performed in Brown-Norway rats using laser light at a wavelength of 689 nm, irradiance of 600 mW/cm(2), and fluence of 25 J/cm(2) after intravenous injection of verteporfin at the doses of 3, 6, and 12 mg/m(2). Apoptotic cells in CNV were detected by TUNEL assay at 1, 3, 6, 15, 24, and 48 hours after PDT. Caspase activation at 1, 3, 6, 15, and 24 hours after PDT was determined by immunohistochemistry (IHC) with a cleaved caspase-3 or -9 antibody. Akt activity was determined by Western blot and IHC with a phosphorylated-Akt (pAkt) antibody. To investigate the roles of Akt in PDT-induced apoptosis, insulin-like growth factor (IGF)-1, an Akt activator, with or without wortmannin, an inhibitor of PI3K-Akt pathway, was injected into the vitreous before PDT. RESULTS. The number of TUNEL-positive cells in CNV increased at 3 hours after PDT and peaked at 6 hours, showing a dose dependence of verteporfin. Caspase activation was detected in TUNEL-positive cells. Dephosphorylation of Akt in CNV occurred within 1 hour. IGF-1 significantly activated Akt and suppressed the number of TUNEL-positive cells in CNV, and the effects of IGF-1 were diminished by wortmannin. CONCLUSIONS. PDT induced caspase-dependent apoptosis in CNV. These results suggest that PDT leads to dephosphorylation of Akt and subsequent activation of the caspase-dependent pathway. Understanding the intracellular signaling mechanisms of apoptosis in PDT may lead to more selective and effective treatment of CNV secondary to age-related macular degeneration. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Retina Serv, Sch Med,Angiogenesis & Laser Labs, Boston, MA 02114 USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Retina Div, Los Angeles, CA 90024 USA. Nagoya City Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Nagoya, Aichi, Japan. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Retina Serv, Sch Med,Angiogenesis & Laser Labs, 243 Charles St, Boston, MA 02114 USA. EM joan_miller@meei.harvard.edu FU NEI NIH HHS [P30 EY014104]; NIAID NIH HHS [AI050775] NR 30 TC 8 Z9 9 U1 0 U2 0 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 2007 VL 48 IS 10 BP 4741 EP 4747 DI 10.1167/iovs.06-1534 PG 7 WC Ophthalmology SC Ophthalmology GA 214SE UT WOS:000249757600046 PM 17898299 ER PT J AU Bassett, IV Giddy, J Nkera, J Wang, B Losina, E Lu, Z Freedberg, KA Walensky, RP AF Bassett, Ingrid V. Giddy, Janet Nkera, Jacques Wang, Bingxia Losina, Elena Lu, Zhigang Freedberg, Kenneth A. Walensky, Rochelle P. TI Routine voluntary HIV testing in Durban, South Africa - The experience from an outpatient department SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 06-09, 2005 CL San Francisco, CA SP Infect Dis Soc Amer DE Africa; HIV; HIV testing; screening; urgent care ID COST-EFFECTIVENESS; SEXUAL-BEHAVIOR; UNITED-STATES; CARE; AIDS; PREVENTION; ATTITUDES; PROGRAM; COUPLES; STIGMA AB Objective: To evaluate the yield of a routine voluntary HIV testing program compared with traditional provider-referred voluntary counseling and testing (VCT) in a hospital-affiliated outpatient department (OPD) in Durban, South Africa. Design and Methods: In a prospective 14-week "standard of care" period, we compared OPD physician logs documenting patient referrals to the hospital VCT site with HIV test registers to measure patient completion of HIV test referral. The standard of care period was followed by a 12-week intervention during which all patients who registered at the OPD were given an educational intervention and offered a rapid HIV test at no charge as part of routine care. Results: During the standard of care period, OPD physicians referred 435 patients aged >= 18 years for HIV testing; 137 (31.5%) of the referred patients completed testing at the VCT site within 4 weeks. Among those tested, 102 (74.5%) were HIV infected. During the intervention period, 1414 adults accepted HIV testing and 1498 declined. Of those tested, 463 (32.7%, 95% confidence interval: 30.3 to 35.3) were HIV infected. Routine HIV testing in the OPD identified 39 new HIV cases per week compared with 8 new cases per week with standard of care testing based on physician referral to a VCT site (P < 0.0001). Conclusions: Routine voluntary HIV testing in an OPD in South Africa leads to significantly higher rates of detection of HIV disease. This strategy should be implemented more widely in high HIV prevalence areas where treatment is available. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. McCord Hosp, Durban, South Africa. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Harvard Ctr AIDS Res CFAR, Boston, MA USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Bassett, IV (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ibassett@partners.org FU NIAID NIH HHS [K24 AI062476, R01 AI058736, T32 AI007433, T32 AI07433, K23 AI001794, K23 AI01794, K23 AI068458, K23 AI068458-01, P30 AI060354] NR 40 TC 58 Z9 60 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2007 VL 46 IS 2 BP 181 EP 186 DI 10.1097/QAI.0b013e31814277c8 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 215LO UT WOS:000249810100008 PM 17667332 ER PT J AU Custovic, A Bush, RK AF Custovic, Adnan Bush, Robert K. TI Two blind mice: New insights into mouse allergy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material ID INNER-CITY CHILDREN; PRESCHOOL-CHILDREN; ASTHMA MORBIDITY; LUNG-FUNCTION; EXPOSURE; SENSITIZATION C1 Univ Manchester, Univ S Manchester Hosp, N W Lung Ctr, NHS Fdn Trust, Manchester, NH USA. Univ Wisconsin, Dept Med, Sect Allergy Immunol Resp Crit & Sleep Med, Madison, WI USA. Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. RP Bush, RK (reprint author), K4-910,CSC 9988,600 Highland Ave, Madison, WI 53792 USA. EM robert.bush@med.va.gov RI Custovic, Adnan/A-2435-2012 OI Custovic, Adnan/0000-0001-5218-7071 NR 14 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2007 VL 120 IS 4 BP 758 EP 759 DI 10.1016/j.jaci.2007.08.018 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 220LH UT WOS:000250157700007 PM 17931560 ER PT J AU Chang, BH Boehmer, U Zhao, Y Sommers, E AF Chang, Bei-Hung Boehmer, Ulrike Zhao, Yue Sommers, Elizabeth TI The combined effect of relaxation response and acupuncture on quality of life in patients with HIV: A pilot study SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; MEDICAL OUTCOMES; NITRIC-OXIDE; COMPLEMENTARY; INFECTION; PAIN; VALIDATION; THERAPIES; EFFICACY; PLACEBO AB Objectives: Treatment advances have transformed human immunodeficiency virus/acquired immune deficiency syndrome (HIV/ AIDS) into a chronic manageable disease; quality of life (QoL) has become an important health outcome. Some studies have shown the individual effects of acupuncture and the relaxation response (RR) in improving QoL of patients with HIV/AIDS. In light of the presumed shared features of acupuncture and the RR, we conducted a pilot study to examine the effects of adding the RR to usual acupuncture treatment on improving the QoL of HIV/AIDS patients. Design: Two-arm double-blind randomized controlled trial. Settings/location and subjects: We enrolled 119 patients with HIV/AIDS (mean age 46 years, 85% male) who had at least 1 of the highly prevalent HIV-related symptoms and who were receiving acupuncture treatment in an acupuncture clinic in Boston, MA. Intervention: We randomized patients into intervention (N = 58) and control (N = 61) groups. All participants received individualized acupuncture treatments prescribed by their acupuncturists. While receiving acupuncture treatment, the intervention group wore earphones to listen to tapes with instructions to elicit the RR followed by soft music that was routinely played in the clinic; the control group listened only to soft music. Outcome measures: Three ( 3) QoL scales: the Medical Outcomes Study HIV health survey, the Functional Assessment of HIV Infection, and the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being, measured at baseline, 4-week, 8-week, and 12-week follow-ups. Results: At the 12-week follow-up, the intervention group showed significant improvements in emotional ( p = 0.0002), spiritual/peace ( p = 0.02), physical ( p < 0.003) and mental health ( p = 0.0003) QoL from baseline. Results of mixed effects regression models indicated linear trends of improvement over time in these dimensions of QoL for the intervention group ( p = 0.02). In the control group, the only significant improvement was observed in the emotional QoL ( p < 0.01). The intervention group showed trends of greater improvements than the control group ( p = 0.07 for 12-week physical health QoL). Conclusions: Data from this pilot trial suggested that adding the RR to acupuncture may enhance improvement in QoL of patients with HIV/AIDS. Further investigation on this putative synergistic effect is warranted. C1 Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02130 USA. VA Boston Hlth Care Syst, Boston, MA USA. Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Pathways Wellness AIDS Care Project, Boston, MA USA. RP Chang, BH (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 150 S Huntington Ave 152H,Bldg 9, Boston, MA 02130 USA. EM bhchang@bu.edu OI Boehmer, Ulrike/0000-0003-0097-5927 FU NCCIH NIH HHS [R21 AT001276, R21 AT001276-02] NR 40 TC 12 Z9 12 U1 0 U2 7 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 2007 VL 13 IS 8 BP 807 EP 815 DI 10.1089/acm.2007.7024 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 229FE UT WOS:000250787600006 PM 17983336 ER PT J AU Reinold, MM Macrina, LC Wilk, KE Fleisig, GS Dun, S Barrentine, SW Ellerbusch, MT Andrews, JR AF Reinold, Michael M. Macrina, Leonard C. Wilk, Kevin E. Fleisig, Glenn S. Dun, Shouchen Barrentine, Steven W. Ellerbusch, Michael T. Andrews, James R. TI Electromyographic analysis of the supraspinatus and deltoid muscles during 3 common rehabilitation exercises SO JOURNAL OF ATHLETIC TRAINING LA English DT Article DE shoulder; dynamic stabilization; empty-can exercises; full-can exercises; prone full-can exercises; rotator cuff; scaption ID ROTATOR CUFF; EMG ANALYSIS; MOMENT ARMS; SHOULDER; ABDUCTION; POSITION; PROGRAM; FORCES; JOINT; EMPTY AB Context: Investigators have observed electromyographic (EMG) activity of the supraspinatus muscle and reported conflicting results. Objective: To quantify EMG activity of the supraspinatus, middle deltoid, and posterior deltoid muscles during exercises commonly used in rehabilitation. Design: One-factor, repeated-measures design. Setting: Controlled laboratory. Patients or Other Participants: Twenty-two asymptomatic subjects (15 men, 7 women) with no history of shoulder injury participated. Main Outcomes Measure(s): The dominant shoulder was tested. Fine-wire EMG electrodes were inserted into the supraspinatus, middle deltoid, and posterior deltoid muscles. The EMG data were collected at 960 Hz for analysis during maximal voluntary isometric contraction (MVIC) and 5 repetitions of 3 exercises: standing elevation in the scapular plane ("full can"), standing elevation in the scapular plane with glenohumeral internal rotation ("empty can"), and prone horizontal abduction at 100 degrees with glenohumeral external rotation ("prone full can"). We calculated 1-way repeated-measures analysis of variance (P <.05) and post hoc 2-tailed, paired t tests to detect significant differences in muscle activity among exercises. Results: No statistical difference existed among the exercises for the supraspinatus. The middle deltoid showed significantly greater activity during the empty-can exercise (77 +/- 44% MVIC) and prone full-can exercise (63 +/- 31% MVIC) than during the full-can exercise (52 +/- 27% MVIC) (P =.001 and .017, respectively). The posterior deltoid showed significantly greater activity during the prone full-can exercise (87 +/- 53% MVIC) than during the full-can (P =.001) and the empty-can (P =.005) exercises and significantly greater activity during the empty-can exercise (54 +/- 24% MVIC) than during the full-can exercise (38 +/- 32% MVIC) (P =.012). Conclusions: While all 3 exercises produced similar amounts of supraspinatus activity, the full-can exercise produced significantly less activity of the deltoid muscles and may be the optimal position to recruit the supraspinatus muscle for rehabilitation and testing. The empty-can exercise may be a good exercise to recruit the middle deltoid muscle, and the prone full-can exercise may be a good exercise to recruit the posterior deltoid muscle. C1 [Reinold, Michael M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reinold, Michael M.] Northeastern Univ, Boston, MA 02115 USA. [Macrina, Leonard C.; Wilk, Kevin E.] Champ Sports Med, Birmingham, AL USA. [Wilk, Kevin E.; Fleisig, Glenn S.; Dun, Shouchen; Barrentine, Steven W.; Andrews, James R.] Amer Sports Med Inst, Birmingham, AL USA. [Ellerbusch, Michael T.] Alabama Orthoped & Spine Ctr, Tuscaloosa, AL USA. [Andrews, James R.] Alabama Sports Med & Orthopaed Ctr, Birmingham, AL USA. RP Reinold, MM (reprint author), MGH Sports Med Ctr, Coordinator Rehabil Res & Educ, Fenway Pk,4 Yawkey Way, Boston, MA 02215 USA. EM mreinold@redsox.com NR 27 TC 55 Z9 56 U1 1 U2 12 PU NATL ATHLETIC TRAINERS ASSOC INC PI DALLAS PA 2952 STEMMONS FREEWAY, DALLAS, TX 75247 USA SN 1062-6050 J9 J ATHL TRAINING JI J. Athl. Train. PD OCT-DEC PY 2007 VL 42 IS 4 BP 464 EP 469 PG 6 WC Sport Sciences SC Sport Sciences GA 251AQ UT WOS:000252343100005 PM 18174934 ER PT J AU Jones, KB Buckwalter, JA DeYoung, BR El-Khoury, GY Dolan, L DeYoung, BR Gannon, FH Inwards, CY Klein, MJ Kyriakos, M McCarthy, EF Siegal, GP Unni, KK El-Khoury, GY Fayad, L Kransdorf, MJ Murphey, MD Panicek, DM Rubin, DA Sundaram, M Vanel, D AF Jones, Kevin B. Buckwalter, Joseph A. DeYoung, Barry R. El-Khoury, Georges Y. Dolan, Lori DeYoung, Barry R. Gannon, Francis H. Inwards, Carrie Y. Klein, Michael J. Kyriakos, Michael McCarthy, Edward F. Siegal, Gene P. Unni, K. Krishnan El-Khoury, Georges Y. Fayad, Laura Kransdorf, Mark J. Murphey, Mark D. Panicek, David M. Rubin, David A. Sundaram, Murali Vanel, Daniel CA SLICED Study Grp TI Reliability of histopathologic and radiologic grading of cartilaginous neoplasms in long bones SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID PROGNOSTIC FACTORS; INTEROBSERVER AGREEMENT; BREAST-CANCER; DNA-PLOIDY; CHONDROSARCOMA; TUMORS; REPRODUCIBILITY; FEATURES; ENCHONDROMA; DIAGNOSIS AB Background: Providing the best treatment options and appropriate prognostic information to patients with cartilaginous neoplasms of long bones depends on distinguishing benign from malignant lesions. Correlative interpretation of imaging, histopathology, and clinical information is the current method for making this distinction, yet the reliability of this approach has not been critically evaluated. This study quantifies the interobserver reliability of the determination of grade for cartilaginous neoplasms among a group of experienced musculoskeletal pathologists and radiologists. Methods: Nine recognized musculoskeletal pathologists and eight recognized musculoskeletal radiologists reviewed forty-six consecutive cases of cartilaginous lesions in long bones that underwent open biopsy or intralesional curettage. All diagnosticians had a bulleted history and preoperative conventional radiographs for review. Pathologists reviewed the original hematoxylin and eosin-stained glass slides from each case. Radiologists reviewed any additional imaging that was available, variably including serial radiographs, magnetic resonance imaging, and computed tomography scans. Each diagnostician classified a lesion as benign, low-grade malignant, or high-grade malignant. Kappa coefficients were calculated as a measure of reliability. Results: Kappa coefficients for interrater reliability were 0.443 for the pathologists and 0.345 for the radiologists (p < 0.0001 for both). Kappa coefficients for a subgroup of cases determined to be high risk by subsequent clinical course were poorer at 0.236 and 0.206, respectively (p < 0.0001 for both). Slightly improved agreement among radiologists was noted for the twenty lesions that had magnetic resonance imaging available (Kappa = 0.437, p < 0.0001), but not for the lesions analyzed with serial plain radiographs or computed tomography scans. Conclusions: This study demonstrates low reliability for the grading of cartilaginous lesions in long bones, even among specialized and experienced pathologists and radiologists. This included low reliability both in differentiating benign from malignant lesions and in differentiating high-grade from low-grade malignant lesions, both of which are critical to the safe treatment of these neoplasms. This may explain in part the wide variation in outcomes reported for chondrosarcomas treated in different medical centers. New diagnostic and grading strategies linked to protocol-driven treatments are needed, but they must be measured against the long-term gold standard of patient outcomes. C1 Univ Iowa Hosp & Clin, Dept Orthopaed & Rehabil, Iowa City, IA 52242 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Baylor Coll Med, Houston, TX 77030 USA. Mayo Clin, Rochester, MN USA. Univ Alabama, Birmingham, AL USA. Washington Univ, St Louis, MO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Jacksonville, FL 32224 USA. Cleveland Clin, Cleveland, OH 44106 USA. Inst Gustave Roussy, Villejuif, France. Mem Sloan Kettering Canc Ctr, New York, NY USA. RP Jones, KB (reprint author), Univ Iowa Hosp & Clin, Dept Orthopaed & Rehabil, 200 Hawkins Dr,01051 John Pappajohn Pavil, Iowa City, IA 52242 USA. EM kbjones@post.harvard.edu RI Siegal, Gene/A-8653-2009; OI Rubin, David/0000-0002-6388-7724; Panicek, David/0000-0003-0302-174X NR 41 TC 7 Z9 7 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 2007 VL 89A IS 10 BP 2113 EP 2123 DI 10.2106/JBJS.F.01530 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 218MI UT WOS:000250019200003 ER PT J AU Yang, SY Chen, W Stashenko, P Li, YP AF Yang, Shuying Chen, Wei Stashenko, Philip Li, Yi-Ping TI Specificity of RGS10A as a key component in the RANKL signaling mechanism for osteoclast differentiation SO JOURNAL OF CELL SCIENCE LA English DT Article DE differential screening; RGS10 RNA interference; [Ca(2+)]i oscillations; osteoclast differentiation; RANKL signaling pathway ID IN-VITRO; TERMINAL DIFFERENTIATION; TRANSCRIPTION FACTOR; SEVERE OSTEOPETROSIS; BONE-RESORPTION; C-FOS; CELLS; PROTEIN; REGULATOR; RECEPTOR AB Significant progress has been made in studies of the mechanisms by which RANKL induces terminal osteoclast differentiation. However, many crucial details in the RANKL-evoked signaling pathway for osteoclast differentiation remain to be defined. We characterized genes specifically expressed in osteoclasts by differential screening of a human osteoclastoma cDNA library, and found that the regulator of G-protein signaling 10A (RGS10A), but not the RGS10B isoform, was specifically expressed in human osteoclasts. The expression of RGS10A is also induced by RANKL in osteoclast precursors and is prominently expressed in mouse osteoclast-like cells. RGS10A silencing by RNA interference blocked intracellular [Ca(2+)] i oscillations, the expression of NFAT2, and osteoclast terminal differentiation in both bone marrow cells and osteoclast precursor cell lines. Reintroduction of RGS10A rescued the impaired osteoclast differentiation. RGS10A silencing also resulted in premature osteoclast apoptosis. RGS10A silencing affected the RANKL-[Ca(2+)] i oscillation-NFAT2 signaling pathway but not other RANKL-induced responses. Our data demonstrate that target components of RGS10A are distinct from those of RGS12 in the RANKL signaling mechanism. Our results thus show the specificity of RGS10A as a key component in the RANKL-evoked signaling pathway for osteoclast differentiation, which may present a promising target for therapeutic intervention. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. EM ypli@forsyth.org RI Yang, Shuying/G-4599-2011 FU NIA NIH HHS [R01 AG048388]; NIAMS NIH HHS [AR-48133-01, R01 AR048133, R01 AR066101, R01 AR044741, AR-44741]; NIDCR NIH HHS [R03 DE016857] NR 41 TC 22 Z9 24 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT 1 PY 2007 VL 120 IS 19 BP 3362 EP 3371 DI 10.1242/jcs.008300 PG 10 WC Cell Biology SC Cell Biology GA 212GZ UT WOS:000249583600005 PM 17881498 ER PT J AU Mathias, JR Dodd, ME Walters, KB Rhodes, J Kanki, JP Look, AT Huttenlocher, A AF Mathias, Jonathan R. Dodd, M. Ernest Walters, Kevin B. Rhodes, Jennifer Kanki, John P. Look, A. Thomas Huttenlocher, Anna TI Live imaging of chronic inflammation caused by mutation of zebrafish Hai1 SO JOURNAL OF CELL SCIENCE LA English DT Article DE cell migration; inflammation; neutrophil; psoriasis; zebrafish ID HEPATOCYTE GROWTH-FACTOR; SELECTIVE CYCLOOXYGENASE-2 INHIBITOR; FACTOR ACTIVATOR INHIBITOR; IN-VIVO; SERINE-PROTEASE; TRANSGENIC ZEBRAFISH; HUMAN NEUTROPHILS; CELL DEVELOPMENT; DANIO-RERIO; T-CELL AB The hallmark of chronic inflammation is the infiltration and persistence of leukocytes within inflamed tissue. Here, we describe the first zebrafish chronic inflammation mutant identified in an insertional mutagenesis screen for mutants that exhibit abnormal tissue distribution of neutrophils. We identified a mutant line with an insertion in the Hepatocyte growth factor activator inhibitor 1 gene ( hai1; also known as Spint1) that showed accumulation of neutrophils in the fin. The mutant embryos exhibited inflammation in areas of epidermal hyperproliferation that was rescued by knock-down of the type II transmembrane serine protease Matriptase 1 (also known as St14), suggesting a novel role for Hai1-Matriptase 1 pathway in regulating inflammation. Using time-lapse microscopy of mutant embryos that express GFP from a neutrophil-specific promoter, we found that individual neutrophils in inflamed tissue displayed random motility characterized by periods of pausing alternating with periods of motility. During periods of persistent movement the cells were highly polarized, while the pausing modes were characterized by a loss of cell polarity. In contrast to responses to acute injury, neutrophils did not exhibit clear retrograde chemotaxis or resolution of inflammation in the mutant. These findings illustrate the utility of zebrafish as a new model system to study chronic inflammation and to visualize immune responses with high resolution in vivo. C1 Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Huttenlocher, A (reprint author), Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. EM huttenlocher@wisc.edu FU NCRR NIH HHS [RR15402-01]; NIDDK NIH HHS [5KO1DK69672]; NIGMS NIH HHS [R01GM074827] NR 54 TC 67 Z9 70 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT 1 PY 2007 VL 120 IS 19 BP 3372 EP 3383 DI 10.1242/jcs.009159 PG 12 WC Cell Biology SC Cell Biology GA 212GZ UT WOS:000249583600006 PM 17881499 ER PT J AU Morioka, T Asilmaz, E Hu, J Dishinger, JF Kurpad, AJ Elias, CF Li, H Elmquist, JK Kennedy, RT Kulkarni, RN AF Morioka, Tomoaki Asilmaz, Esra Hu, Jiang Dishinger, John F. Kurpad, Amarnath J. Elias, Carol F. Li, Hui Elmquist, Joel K. Kennedy, Robert T. Kulkarni, Rohit N. TI Disruption of leptin receptor expression in the pancreas directly affects beta cell growth and function in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INSULIN-RESISTANCE; DIABETIC MICE; GLUCOSE-INTOLERANCE; MESSENGER-RNA; HYPERINSULINEMIA; LEADS; RAT; INHIBITION; DELETION; OBESITY AB Obesity is characterized by hyperinsulinemia, hyperleptinemia, and an increase in islet volume. While the mechanisms that hasten the onset of diabetes in obese individuals are not known, it is possible that the adipose-derived hormone leptin plays a role. In addition to its central actions, leptin exerts biological effects by acting in peripheral tissues including the endocrine pancreas. To explore the impact of disrupting leptin signaling in the pancreas on beta cell growth and/or function, we created pancreas-specific leptin receptor (ObR) KOs using mice expressing Cre recombinase under the control of the pancreatic and duodenal homeobox 1 (Pdx1) promoter. The KOs exhibited improved glucose tolerance due to enhanced early-phase insulin secretion, and a greater beta cell mass secondary to increased beta cell size and enhanced expression and phosphorylation of p70S6K. Similar effects on p70S6K were observed in MIN6 beta cells with knockdown of the ObR gene, suggesting crosstalk between leptin and insulin signaling pathways. Surprisingly, challenging the KOs with a high-fat diet led to attenuated acute insulin secretory response to glucose, poor compensatory islet growth, and glucose intolerance. Together, these data provide direct genetic evidence, from a unique mouse model lacking ObRs only in the pancreas, for a critical role for leptin signaling in islet biology and suggest that altered leptin action in islets is one factor that contributes to obesity-associated diabetes. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Rockefeller Univ, Mol Genet Lab, New York, NY 10021 USA. Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Div Endocrinol & Metab, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Internal Med, Ctr Hypothalam Res, Dallas, TX USA. Univ Sao Paulo, Inst Biomed Sci, Sao Paulo, Brazil. RP Kulkarni, RN (reprint author), Room 602,1 Joslin Pl, Boston, MA 02215 USA. EM Rohit.Kulkarni@joslin.harvard.edu RI Kennedy, Robert/G-9095-2016; OI Kennedy, Robert/0000-0003-2447-7471; Elias, Carol F/0000-0001-9878-9203 FU NIDDK NIH HHS [R21 DK75766, P30 DK036836, P30 DK36836, R01 DK067536, R01 DK67536, R21 DK075766, R37 DK046960, R37 DK46960] NR 42 TC 129 Z9 135 U1 0 U2 3 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 2007 VL 117 IS 10 BP 2860 EP 2868 DI 10.1172/JCI30910 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 216QP UT WOS:000249894400017 PM 17909627 ER PT J AU Ausiello, D AF Ausiello, Dennis TI Science education and communication SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Ausiello, D (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM dausiello@partners.org NR 6 TC 4 Z9 4 U1 2 U2 8 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 2007 VL 117 IS 10 BP 3128 EP 3130 DI 10.1172/JCI33385 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 216QP UT WOS:000249894400043 PM 17909633 ER PT J AU Truman, CJ Goldberg, JF Ghaemi, SN Baldassano, CF Wisniewski, SR Dennehy, EB Thase, ME Sachs, GS AF Truman, Christine J. Goldberg, Joseph F. Ghaemi, S. Nassir Baldassano, Claudia F. Wisniewski, Stephen R. Dennehy, Ellen B. Thase, Michael E. Sachs, Gary S. TI Self-reported history of manic/hypomanic switch associated with antidepressant use: Data from the systematic treatment enhancement program for bipolar disorder (STEP-BD) SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 156th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 2003 CL SAN FRANCISCO, CA SP Amer Psychiat Assoc ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; WEEKLY SYMPTOMATIC STATUS; INDUCED MANIA; CYCLE ACCELERATION; DEPRESSED-PATIENTS; MOOD-STABILIZERS; NATURAL-HISTORY; I DISORDER; DSM-IV; BUPROPION AB Objective: Antidepressant safety and efficacy remain controversial for the treatment of bipolar depression. The present study utilized data from the National Institute of Mental Health Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) to examine the prevalence and clinical correlates of self-reported switch into mania/hypomania during antidepressant treatment. Method: Antidepressant treatment histories were examined from intake assessments for the first 500 subjects enrolled into the STEP-BD) between November 1999 and November 2000. Affective switch was defined as a report of mania, hypomania, or mixed episodes within the first 12 weeks of having started an antidepressant. Demographic and clinical characteristics were compared for subjects with or without a history of acute switch during antidepressant treatment. Results: Among the 338 subjects with prior antidepressant treatment and complete data on switch event outcomes, 44% reported at least 1 such occurrence. Patients with a shorter duration of illness (odds ratio [OR] = 1.02, 95% CI = 1.01 to 1.04) and a history of multiple antidepressant trials (OR = 1.73. 95% CI = 1.38 to 2.16) were more likely to report a history of switch than other patients. A significantly increased risk for affective polarity switch was identified in patients who had ever switched to mania/hypomania while taking tricyclic antidepressants (OR = 7.80 95% CI = 1.56 to 28.9). serotonin reuptake inhibitors (OR = 3.73 95% CI = 1.98 to 7.05), or bupropion (OR = 4.28. 95% CI = 1.72 to 10.6). Switch was less common during treatment with electroconvulsive therapy or monoamine oxidase inhibitors than other antidepressants. Conclusions: Antidepressants are associated with the potential risk for treatment-emergent mania or hypomania, particularly in bipolar patients with short illness duration, multiple past antidepressant trials, and past experience of switch with at least one antidepressant. C1 Silver Hill Hosp, Affect Disorders Program, New Canaan, CT 06840 USA. Finnery Psychotherapy Assoc, Norfolk, VA USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Emory Univ, Dept Psychiat & Behav Sci, Bipolar Disorder Res Program, Atlanta, GA 30322 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Partners Bipolar Treatment Ctr, Boston, MA USA. RP Goldberg, JF (reprint author), Silver Hill Hosp, Affect Disorders Program, 208 Valley Rd, New Canaan, CT 06840 USA. EM JFGoldberg@yahoo.com RI Ghaemi, Nassir/J-4934-2013; OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH80001] NR 30 TC 75 Z9 79 U1 0 U2 6 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 2007 VL 68 IS 10 BP 1472 EP 1479 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 226XB UT WOS:000250620700002 PM 17960960 ER PT J AU Mensinger, JL Lynch, KG TenHave, TR Mckay, JR AF Mensinger, Janell Lynn Lynch, Kevin G. TenHave, Thomas R. Mckay, James R. TI Mediators of telephone-based continuing care for alcohol and cocaine dependence SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE substance abuse; aftercare treatment; continuing care; telephone monitoring; longitudinal mediation analysis ID SUBSTANCE USE; DRINKING BEHAVIOR; CLINICAL-TRIALS; SOCIAL SUPPORT; USE DISORDERS; GROUP-THERAPY; SELF-REPORTS; OUTCOMES; RELAPSE; RELIABILITY AB A previous randomized trial with 224 alcohol and/or cocaine addicts who had completed an initial phase of treatment indicated that 12 weeks of telephone-based continuing care yielded higher abstinence rates over 24 months than did group counseling continuing care. The current study examined mediators of this treatment effect. Results suggested that self-help involvement during treatment and self-efficacy and commitment to abstinence 3 months after treatment mediated subsequent abstinence outcomes. These analyses controlled for substance use prior to the assessment of mediators. Conversely, there was no evidence that self-help beliefs or social support mediated the treatment effect. These results are consistent with a model in which treatment effects are first accounted for by changes in behavior, followed by changes in self-efficacy and in commitment to abstinence. C1 Reading Hosp Med Ctr, Clin Res Unit, Reading, PA 19612 USA. Univ Penn, Dept Psychiat, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Mensinger, JL (reprint author), Reading Hosp Med Ctr, Clin Res Unit, Reading, PA 19612 USA. EM mensingerj@readinghospital.org RI Mensinger, Janell/F-1175-2014 FU NIAAA NIH HHS [R01-AA10341]; NIDA NIH HHS [R01-DA10262]; NIMH NIH HHS [R01 MH078016-01A2, R01 MH078016, R01-MH-61892, T32-MH-065218] NR 55 TC 18 Z9 18 U1 2 U2 5 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2007 VL 75 IS 5 BP 775 EP 784 DI 10.1037/0022-006X.75.5.775 PG 10 WC Psychology, Clinical SC Psychology GA 214PG UT WOS:000249750000011 PM 17907859 ER PT J AU Wilcox, SR Thomas, S Brown, DFM Nadel, ES AF Wilcox, Susan R. Thomas, Stephen Brown, David F. M. Nadel, Eric S. TI Gastrointestinal parasite SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID NEUROCYSTICERCOSIS C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 12 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 2007 VL 33 IS 3 BP 277 EP 280 DI 10.1016/j.jemermed.2007.07.020 PG 4 WC Emergency Medicine SC Emergency Medicine GA 230OY UT WOS:000250887000009 PM 17976556 ER PT J AU Rhoads, RP Kim, JW Van Amburgh, ME Ehrhardt, RA Frank, SJ Boisclair, YR AF Rhoads, R. P. Kim, J. W. Van Amburgh, M. E. Ehrhardt, R. A. Frank, S. J. Boisclair, Y. R. TI Effect of nutrition on the GH responsiveness of liver and adipose tissue in dairy cows SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE RECEPTOR; MESSENGER-RIBONUCLEIC-ACID; NEGATIVE-ENERGY BALANCE; LACTATING COWS; FACTOR-I; IGF-I; BOVINE SOMATOTROPIN; SKELETAL-MUSCLE; INSULIN-RESISTANCE; HEPATIC TISSUE AB Dairy cows enter a period of energy insufficiency after parturition. In liver, this energy deficit leads to reduced expression of the liver-specific GH receptor transcript (GHR1A) and decreased GHR abundance. As a consequence, hepatic processes stimulated by GH, such as IGF-I production, are reduced. In contrast, adipose tissue has been assumed to remain fully GH responsive in early lactation. To determine whether energy insufficiency causes contrasting changes in the GH responsiveness of liver and adipose tissue, six lactating dairy cows were treated for 4 days with saline or bovine GH when adequately fed (AF, 120% of total energy requirement) or underfed (UF, 30% of maintenance energy requirement). AF cows mounted robust GH responses in liver(plasma IGF-I and IGF-I mRNA) and adipose tissue (epinephrine-stimulated release of non-esterified fatty acids in plasma, IGF-I mRNA, and p85 regulatory subunit of phosphatidylinositol 3-kinase mRNA). Reductions of these responses were seen in the liver and adipose tissue of UF cows and were associated with decreased GHR abundance. Reduced GHR abundance occurred without corresponding reductions of GHR1A transcripts in liver or total GHR transcripts in adipose tissue. In contrast, undernutrition did not alter the abundance of proteins involved in the early post-receptor signaling steps. Thus, a feed restriction reproducing the energy deficit of early lactation depresses GH actions not only in liver but also in adipose tissue. It remains unknown whether a similar reduction of GH action occurs in the adipose tissue of early lactating dairy cows. C1 Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. Univ Arizona, Dept Anim Sci, Tucson, AZ 85721 USA. Gyeongsang Natl Univ, Coll Agr & Life Sci, Dept Dairy Sci, Div Appl Life Sci, Jinju 660701, South Korea. Birmingham VAMC, Med Serv, Endocrinol Sect, Birmingham, AL 35233 USA. Univ Alabama, Dept Med, Div Endocrinol Diabet & Metab, Birmingham, AL 35294 USA. RP Boisclair, YR (reprint author), Cornell Univ, Dept Anim Sci, 259 Morrison Hall, Ithaca, NY 14853 USA. EM yrb1@cornell.edu RI Rhoads, Robert/F-2861-2016 OI Rhoads, Robert/0000-0002-5205-5834 FU NIDDK NIH HHS [DK51624, DK58259] NR 50 TC 25 Z9 25 U1 0 U2 2 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD OCT PY 2007 VL 195 IS 1 BP 49 EP 58 DI 10.1677/JOE-07-0068 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 224HX UT WOS:000250439200006 PM 17911396 ER PT J AU Wu, Q Zhou, Y Chen, LF Shi, JD Wang, CY Miao, L Mocker, H Park, I Lee, C Zhang, J AF Wu, Quan Zhou, Ying Chen, Linfeng Shi, Jiandang Wang, Chun-Yu Miao, Lin Mocker, Helmut Park, Irwin Lee, Chung Zhang, Ju TI Benign prostatic hyperplasia (BPH) epithelial cell line BPH-1 induces aromatase expression in prostatic stromal cells via prostaglandin E2 SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CYP19; GENE; ESTROGEN; AROMATIZATION; CARCINOMA; ESTRADIOL; ANDROGEN; CANCER AB Estradiol (E2) level in stroma of benign prostatic hyperplasia (BPH) increases with age, and this increase was associated with an elevated expression of aromatase in prostatic stromal cells (PrSCs). Here, we showed that conditioned medium (CM) of BPH-1 (a benign hyperplastic prostatic epithelial cell line), but not of prostate cancer cell lines (LNCaP, DU-1 45, and PC-3), stimulates aromatase expression in PrSCs. Cyclooxygenase-2 (COX-2) mRNA level in BPH-1, as well as prostaglandin E2 (PGE2) concentration in BPH-1 CM, was significantly higher than that of prostate cancer cell lines. CM of BPH-1 treated with NS-398 (a specific inhibitor of COX-2) failed to stimulate aromatase expression in PrSCs. And PGE2 can stimulate aromatase expression in PrSCs. Our data suggested that BPH-1 induced aromatase expression in PrSCs through the production of PGE2 in a paracrine mechanism. C1 Nankai Univ, Inst Mol Biol, Minist Educ, Bioact Mat Key Lab, Tianjin 300071, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Innsbruck Med Univ, Dept Urol, A-6020 Innsbruck, Austria. Northwestern Univ, Feinburg Sch Med, Chicago, IL 60611 USA. RP Zhang, J (reprint author), Nankai Univ, Inst Mol Biol, Minist Educ, Bioact Mat Key Lab, Tianjin 300071, Peoples R China. EM zhangju@nankai.edu.cn NR 18 TC 10 Z9 11 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD OCT PY 2007 VL 195 IS 1 BP 89 EP 94 DI 10.1677/JOE-06-0181 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 224HX UT WOS:000250439200010 PM 17911400 ER PT J AU Renlund, N O'Neill, FH Zhang, L Sidis, Y Teixeira, J AF Renlund, Nina O'Neill, Francis H. Zhang, LiHua Sidis, Yisrael Teixeira, Jose TI Activin receptor-like kinase-2 inhibits activin signaling by blocking the binding of activin to its type II receptor SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID BETA; SUBSTANCE; IDENTIFICATION; ALK2; TESTOSTERONE; EXPRESSION; COMPLEXES; PROMOTER; ELEMENTS; HORMONE AB Activin receptor-like kinase-2 (Alk2) has been shown to be a promiscuous type I receptor for the transforming growth factor P (TGF beta) family of growth and differentiation factors, Such as activin, bone morphogenetic proteins, and Mullerian inhibiting substance (MIS). We have studied the putative role of Alk2 in activin signaling using MA-10 cells, a mouse transformed Leydig cell line, in which endogenous expression of cytochrome P450 c17 hydroxylase/C17-20 lyase mRNA is inhibited by both MIS and activin A. Overexpression of Alk2 in MA-10 cells inhibited the activation of the activin-responsive CAGA-luciferase reporter and, conversely, transfection of siRNA for Alk2 increased the response. In contrast, overexpression of the MIS type 11 receptor in MA-10 cells increased the activin-mediated induction of CAGA-luciferase approximately fivefold, which we hypothesized occurs by MIS type 11 receptor sequestering endogenous Alk2. Binding experiments with 125 I-labeled activin show that the underlying mechanism of Alk2-mediated inhibition of activin signaling involves Alk2 blocking the access of activin to its type 11 receptor, which we show can bind Alk2 in the absence of ligand. These results show that the complement of other type I receptors in addition to the ligand-specific type I receptor can provide an important mechanism for modulating cell-specific responses to members of the TGF beta family. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Teixeira, J (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Thier 913,55 Fruit St, Boston, MA 02114 USA. EM teixeiraou@helix.mgh.harvard.edu OI Teixeira, Jose/0000-0002-6438-5064 FU NICHD NIH HHS [U54 HD28138] NR 27 TC 16 Z9 16 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD OCT PY 2007 VL 195 IS 1 BP 95 EP 103 DI 10.1677/JOE-07-0281 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 224HX UT WOS:000250439200011 PM 17911401 ER PT J AU Ando, T Latif, R Davies, TF AF Ando, Takao Latif, Rauf Davies, Terry F. TI Antibody-induced modulation of TSH receptor post-translational processing SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID HUMAN THYROTROPIN RECEPTOR; THYROID-STIMULATING ANTIBODY; AMINO-ACID MOTIF; INTRAMOLECULAR CLEAVAGE; MONOCLONAL-ANTIBODIES; HORMONE-RECEPTOR; SITE 1; ECTODOMAIN; BINDING; CELLS AB The post-translational processing of the TSH receptor (TSHR) includes intra-molecular cleavage with the loss of a 50 amino, acid ectodomain region and the formation of two subunits (alpha and beta), followed by likely a subunit shedding. TSHR antibodies (TSHR-Abs), which are directed at the ectodomain, may influence thyroid function by stimulating or inhibiting TSHR, signaling or may bind without any such influence (the neutral group of antibodies). When we examined the characteristics of a series of monoclonal TSHR-Abs, we found that many were able to inhibit receptor cleavage and enhance TSHR expression. This was especially apparent with the neutral type of TSHR-Abs directed to the cleaved region of the ectodomain (aa 316-366). Indeed, such inhibition appeared to be epitope dependent with TSHR-Abs directed to regions after residues 335-354 showing no such activity. We propose that this aberrant process, whereby TSHR-Abs influence antigen processing, is a novel mechanism for the maintenance and exacerbation of autoimmune thyroid disease. C1 CUNY Mt Sinai Sch Med, James J Peters VA Med Ctr, Thyroid Res Unit, New York, NY 10029 USA. RP Davies, TF (reprint author), CUNY Mt Sinai Sch Med, James J Peters VA Med Ctr, Thyroid Res Unit, Box 1055,1 Gustave L Levy Pl, New York, NY 10029 USA. EM terry.davies@mssm.edu FU NIDDK NIH HHS [DK069713, DK052464] NR 32 TC 11 Z9 12 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD OCT PY 2007 VL 195 IS 1 BP 179 EP 186 DI 10.1677/JOE-07-0058 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 224HX UT WOS:000250439200019 PM 17911409 ER PT J AU Eisner, B Cantwell, C Gervais, D Arellano, R Mueller, P Samir, A Uppot, R McGovern, F AF Eisner, Brian Cantwell, Colin Gervais, Debra Arellano, Ronald Mueller, Peter Samir, Anthony Uppot, Raul McGovern, Francis TI Protecting the ureter and ureteropelvic junction during radiofrequency ablation: A pilot study using cooled D5W retrograde pyeloperfusion SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Eisner, Brian; McGovern, Francis] Massachusetts Gen Hosp, Harvard Med Sch, Dept Urol, Boston, MA 02114 USA. [Cantwell, Colin; Gervais, Debra; Arellano, Ronald; Mueller, Peter; Samir, Anthony; Uppot, Raul] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 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 0892-7790 J9 J ENDOUROL JI J. Endourol. PD OCT PY 2007 VL 21 SU 1 BP A261 EP A261 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 228UW UT WOS:000250759101484 ER PT J AU Eisner, B Patel, P Otite, U Devarajan, R AF Eisner, Brian Patel, Prashant Otite, Ugo Devarajan, Raghuram TI "Blind coning" - Using the stone cone for removal of distal ureteric calculi SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Eisner, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Patel, Prashant; Otite, Ugo; Devarajan, Raghuram] Sandwell & West Birmingham Hosp NHS Trust, Birmingham, W Midlands, England. 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 0892-7790 J9 J ENDOUROL JI J. Endourol. PD OCT PY 2007 VL 21 SU 1 BP A109 EP A109 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 228UW UT WOS:000250759100479 ER PT J AU Eisner, B Pedro, R Namasivayam, S Sahani, D Dretler, S Monga, M AF Eisner, Brian Pedro, Renato Namasivayam, Saravanan Sahani, Dushyant Dretler, Stephen Monga, Manoj TI Ureteral stone size and location: Impact on ureteral dilation SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Eisner, Brian; Dretler, Stephen] Massachusetts Gen Hosp, Harvard Med Sch, Dept Urol, Boston, MA 02114 USA. [Pedro, Renato; Monga, Manoj] Univ Minnesota, Dept Urol Surg, Minneapolis, MN USA. [Namasivayam, Saravanan; Sahani, Dushyant] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 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 0892-7790 J9 J ENDOUROL JI J. Endourol. PD OCT PY 2007 VL 21 SU 1 BP A83 EP A83 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 228UW UT WOS:000250759100364 ER PT J AU Eisner, B Iqbal, A Namasaviyam, S Catalano, O Dretler, S Sahani, D AF Eisner, Brian Iqbal, Ahsan Namasaviyam, Saravanan Catalano, Onoftio Dretler, Stephen Sahani, Dushyant 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 Meeting Abstract C1 [Eisner, Brian; Dretler, Stephen] Massachusetts Gen Hosp, Harvard Med Sch, Dept Urol, Boston, MA 02114 USA. [Iqbal, Ahsan; Namasaviyam, Saravanan; Catalano, Onoftio; Sahani, Dushyant] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02114 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 0892-7790 J9 J ENDOUROL JI J. Endourol. PD OCT PY 2007 VL 21 SU 1 BP A51 EP A51 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 228UW UT WOS:000250759100222 ER PT J AU Lee, HJ Box, GN Deane, LA Elchico, ER Taylor, MB Alipanah, R Abraham, JB Andrade, LC Eisner, B McDougall, EM Clayman, RV AF Lee, Hak J. Box, Geoffrey N. Deane, Leslie A. Elchico, Eric R. Taylor, Mike B. Alipanah, Reza Abraham, Jose B. Andrade, Lorena C. Eisner, Brian McDougall, Elspeth M. Clayman, Ralph V. TI In-vitro evaluation of the stone cone and NTrap in preventing retropulsion and improving the fragmentation of holmium: Yag ureterolithotripsy SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Lee, Hak J.] Univ Calif Irvine, Orange, CA 92668 USA. [Eisner, Brian] Massachusetts Gen Hosp, Boston, MA 02114 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 0892-7790 J9 J ENDOUROL JI J. Endourol. PD OCT PY 2007 VL 21 SU 1 BP A163 EP A163 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 228UW UT WOS:000250759101048 ER PT J AU Chen, D Lew, R Hershman, W Orlander, J AF Chen, Daniel Lew, Robert Hershman, Warren Orlander, Jay TI A cross-sectional measurement of medical student empathy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE empathy; medical student education; physician attitudes ID PHYSICIAN-PATIENT COMMUNICATION; PRIMARY-CARE; PSYCHOMETRIC DATA; JEFFERSON SCALE; GENDER; DOCTOR; MOOD; SATISFACTION; MALPRACTICE; ENABLEMENT AB BACKGROUND: Empathy is important in the physician-patient relationship. Prior studies have suggested that physician empathy may decline with clinical training. OBJECTIVE: To measure and examine student empathy across medical school years. DESIGN AND PARTICIPANTS: A cross-sectional study of students at Boston University School of Medicine in 2006. Incoming students plus each class near the end of the academic year were surveyed. MEASUREMENTS: The Jefferson Scale of Physician Empathy-Student Version (JSPE-S), a validated 20-item self-administered questionnaire with a total score ranging from 20 to 140. JSPE-S scores were controlled for potential confounders such as gender, age, anticipated financial debt upon graduation, and future career interest. RESULTS: 658 students participated in the study (81.4% of the school population). The first-year medical student class had the highest empathy scores (118.5), whereas the fourth-year class had the lowest empathy scores (106.6). Measured empathy differed between second- and third-year classes (118.2 vs 112.7, P < .001), corresponding to the first year of clinical training. Empathy appears to increase from the incoming to the first-year class (115.5 vs 118.5, P = .02). Students preferring people-oriented specialties had higher empathy scores than students preferring technology-oriented specialties (114.6 vs 111.4, P = .002). Female students were more likely than male students to choose people-oriented specialties (51.5 vs 26.9%, P < .001). Females had higher JSPE-S scores than males (116.5 vs 112.1, P < .001). Age and debt did not affect empathy scores. CONCLUSIONS: Empathy scores of students in the preclinical years were higher than in the clinical years. Efforts are needed to determine whether differences in empathy scores among the classes are cohort effects or represent changes occurring in the course of medical education. Future research is needed to confirm whether clinical training impacts empathy negatively, and, if so, whether interventions can be designed to mitigate this impact. C1 Boston Univ, Sch Med, Sect Gen Internal Med, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. VA Boston Healthcare Syst, Med Serv, Boston, MA USA. VA Boston Healthcare Syst, MAVERIC, Boston, MA USA. RP Chen, D (reprint author), Boston Univ, Sch Med, Sect Gen Internal Med, Evans Dept Med, 91 E Concord St,MAT 2, Boston, MA 02118 USA. EM daniel.chen@bmc.org OI Orlander, Jay/0000-0003-0204-8449; Chen, Daniel/0000-0001-6672-6814 NR 41 TC 108 Z9 115 U1 4 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2007 VL 22 IS 10 BP 1434 EP 1438 DI 10.1007/s11606-007-0298-x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 213FF UT WOS:000249650900009 PM 17653807 ER PT J AU Kressin, NR Saha, S Weaver, F Rubenstein, L Weinberger, M AF Kressin, Nancy R. Saha, Somnath Weaver, Frances Rubenstein, Lisa Weinberger, Morris TI Career and time management strategies for clinical and health services researchers SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article ID GENERAL INTERNAL-MEDICINE; INVESTIGATORS C1 Ctr Hlth Qual Outcomes & Econ Res, Dept Vet Affairs, Bedford, MA 01730 USA. Boston Univ, Sch Med, Sect Gen Internal Med, Boston, MA 02215 USA. Portland VA Med Ctr, Sect Gen Internal Med, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Hines VA Hosp, Ctr Management Complex Chron Care & Spinal Cord I, Hines, IL USA. Northwestern Univ, Inst Healthcare Studies, Chicago, IL 60611 USA. Sepulveda Ambulatory Care Ctr & Nursing Home, VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Excellence Study Healthcare Provider, Sepulveda, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Durham VAMC, Ctr Excellence Hlth Serv Res Primary Care, Durham, NC USA. Univ N Carolina, Dept Hlth Policy & Adm, Chapel Hill, NC 27514 USA. RP Kressin, NR (reprint author), Ctr Hlth Qual Outcomes & Econ Res, Dept Vet Affairs, 200 Springs Rd Bldg 70 152, Bedford, MA 01730 USA. EM nkressin@bu.edu OI Kressin, Nancy/0000-0003-2767-4286 NR 11 TC 0 Z9 0 U1 0 U2 1 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 2007 VL 22 IS 10 BP 1475 EP 1478 DI 10.1007/s11606-007-0337-7 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 213FF UT WOS:000249650900017 PM 17717715 ER PT J AU Pasquale, LR Rosner, BA Hankinson, SE Kang, JH AF Pasquale, Louis R. Rosner, Bernard A. Hankinson, Susan E. Kang, Jae Hee TI Attributes of female reproductive aging and their relation to primary open-angle glaucoma: A prospective study SO JOURNAL OF GLAUCOMA LA English DT Article DE female reproductive aging; menopausal status; age at menopause; postmenopausal hormone use; primary open-angle glaucoma; estrogen; progestin ID HORMONE REPLACEMENT THERAPY; NITRIC-OXIDE SYNTHASE; ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; BALTIMORE EYE SURVEY; INTRAOCULAR-PRESSURE; POSTMENOPAUSAL WOMEN; BREAST-CANCER; OCULAR HYPERTENSION; GANGLION-CELLS AB Purpose: We investigated the relation between age at menopause, postmenopausal hormone (PMH) use, and incident primary open-angle glaucoma (POAG). Methods: We followed 66,417 women in the Nurses' Health Study prospectively from 1980 to 2002. Eligible participants were > 40 years old, free of POAG at baseline, provided information on menopausal status, and reported receiving eye examinations during follow-up. Relevant exposure data and POAG risk factors were updated using biennial questionnaires. We identified 447 POAG cases during follow-up. We used proportional hazards models to calculate multivariable rate ratios (MVRR) of POAG and 95% confidence intervals. Results: Among postmenopausal women overall, entering menopause before age 45 [MVRR = 0.85 (0.63 to 1.14)] or at age > 54 [MVRR = 0.84 (0.60 to 1.18)] was not significantly associated with POAG compared with entering menopause at age 50 to 54. However, in secondary analysis, among postmenopausal women aged > 65 years, entering menopause at age > 54 years was associated with reduced risk of POAG compared with entering menopause at age 50 to 54 [MVRR = 0.53 (0.32 to 0.89)]. Overall, compared with never use of PMH, past PMH use [MVRR = 0.84 (0.61 to 1.18)], and current PMH use [MVRR = 0.89 (0.70 to 1.13)] was not significantly associated with POAG. In secondary analysis, compared with never use of PMH, current use of estrogen with progestin [MVRR = 0.58 (0.36 to 0.94)] was associated with a reduced risk of POAG characterized by intraocular pressure > 21 mm Hg before visual field loss; current use estrogen alone [MVRR = 0.93 (0.63 to 1.35)] was not significantly associated. Conclusions: These data suggest a possible role for declining sex hormones in POAG pathogenesis. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Sch Med, Boston, MA 02115 USA. RP Pasquale, LR (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Louis_Pasquale@meei.harvard.edu FU NCI NIH HHS [CA55075, CA87969]; NEI NIH HHS [EY015473, EY09611]; NHLBI NIH HHS [HL35464] NR 53 TC 31 Z9 31 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD OCT-NOV PY 2007 VL 16 IS 7 BP 598 EP 605 PG 8 WC Ophthalmology SC Ophthalmology GA 231HS UT WOS:000250938100004 PM 18091177 ER PT J AU Forthman, C Henket, M Ring, DC AF Forthman, Christopher Henket, Marjolijn Ring, David C. TI Elbow dislocation with intra-articular fracture: The results of operative treatment without repair of the medial collateral ligament SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE elbow fracture-dislocation; traumatic instability; operative treatment ID RADIAL HEAD; PROSTHETIC REPLACEMENT; ROTATORY INSTABILITY; CORONOID PROCESS; JOINT; STABILITY; EXCISION; RECONSTRUCTION; ARTHROPLASTY; INJURIES AB Purpose: To determine the effectiveness of a protocol for the treatment of fracture-dislocations of the elbow based on the concept that, if dislocation of the elbow with associated fractures can be made to resemble a simple elbow dislocation by repairing or reconstructing the fractured structures, repair of the medial collateral ligament (MCL) will not be necessary. Methods: Over a 5-year period, a single surgeon operated on 34 patients with a posterior dislocation of the elbow associated with one or more intra-articular fractures. The mean age of these 19 men and 15 women was 48 years. Associated fractures included the capitellum, trochlea, and lateral epicondyle in 3 patients; the olecranon in 1 patient; and the radial head in 30 patients (with concomitant fracture of the coronoid process-the so-called "terrible triad" of the elbow-in 22 patients, and concomitant fracture of the coronoid and olecranon in 1 patient). Operative treatment consisted of open reduction internal fixation (ORIF) or prosthetic replacement of all fractures and reattachment of the origin of the lateral collateral ligament (LCL) complex to the lateral epicondyle. The MCL was not repaired. Results: Two patients (1 with a terrible triad injury and 1 with fracture of the capitellum and trochlea) had postoperative instability related to noncompliance, had reconstructive procedures, and were considered failures. An average of 32 months after injury, the remaining 32 patients regained an average of 1200 ulnohumeral motion and 1420 forearm rotation. Twenty-five of 34 patients (74%) had good or excellent results according to the system of Broberg and Morrey. Patients with terrible triad injuries had an average of 117 degrees ulnohumeral motion and 137 degrees forearm rotation, and 17 of 22 patients (77%) had good or excellent results. Conclusions: MCL repair is unnecessary in the treatment of dislocation of the elbow with associated intra-articular fractures, provided that the articular fractures and the LCIL are repaired or reconstructed. C1 Curtis Natl Hand Ctr, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, DC (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 42 TC 69 Z9 84 U1 0 U2 9 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 2007 VL 32A IS 8 BP 1200 EP 1209 DI 10.1016/j.jhsa.2007.06.019 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 223PZ UT WOS:000250386100012 PM 17923304 ER PT J AU Maheshwari, S Sarraj, A Kramer, J El-Serag, HB AF Maheshwari, Shail Sarraj, Amrou Kramer, Jennifer El-Serag, Hashem B. TI Oral contraception and the risk of hepatocellular carcinoma SO JOURNAL OF HEPATOLOGY LA English DT Article DE epidemiology; risk factors; meta-analysis; hormones; liver cancer ID PRIMARY LIVER-CANCER; STEROIDS; TUMORS; WOMEN AB Backgrounds/Aims: We performed a meta-analysis of observational epidemiological studies to examine the association between oral contraceptives (OC) and hepatocellular carcinoma (HCC). Methods:Two independent researchers conducted PubMed searches followed by systematic abstraction of studies that compared OC use between patients with HCC and a group of controls. Pooling of ORs was conducted using a random effects model. Heterogeneity and publication bias among studies were examined. Results: Twelve case-control studies that included 739 cases and 5223 controls met the inclusion and exclusion criteria. The pooled estimate of ORs (age- and sex-matched only) from all 12 studies was 1.57 (95% CI = 0.96-2.54, p = 0.07) with a heterogeneity of I-2 = 39.9. Exclusion of one large multi-national European study decreased the heterogeneity to I-2 = 16.9 and increased the pooled OR to 1.70 (95% CI = 1.12-2.59, p = 0.01). Eight studies reported adjusted ORs (in addition to age and sex); the pooled estimate was 1.45 (95% CI = 0.93-2.27, p = 0.11) with a heterogeneity of I-2 = 20.4. Only few studies identified or adjusted for other HCC risk factors. Six studies showed a significant 2- to 20-fold increase in HCC risk with longer durations of OC use; however, the reporting was too inconsistent to allow meta-analysis. Conclusions: The evidence is inconclusive to establish a relation between oral contraceptives and the risk of hepatocellular carcinoma. Future studies should focus on the duration, intermittency, and recency of OC use. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res, Gastroenterol Sect, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res, Gastroenterol Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU PHS HHS [56338] NR 26 TC 43 Z9 46 U1 2 U2 7 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 2007 VL 47 IS 4 BP 506 EP 513 DI 10.1016/j.jhep.2007.03.015 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 218OQ UT WOS:000250025200013 PM 17462781 ER PT J AU Brau, N Fox, RK Xiao, PY Marks, K Naqvi, Z Taylor, LE Trikha, A Sherman, M Sulkowski, MS Dieterich, DT Rigsby, MO Wright, TL Hernandez, MD Jain, MK Khatri, GK Sterling, RK Bonacini, M Martyn, CA Aytaman, A Llovet, JM Brown, ST Bini, EJ AF Braeu, Norbert Fox, Rena K. Xiao, Peiying Marks, Kristen Naqvi, Zeenat Taylor, Lynn E. Trikha, Anita Sherman, Morris Sulkowski, Mark S. Dieterich, Douglas T. Rigsby, Michael O. Wright, Teresa L. Hernandez, Maria D. Jain, Mamta K. Khatri, Gajendra K. Sterling, Richard K. Bonacini, Maurizio Martyn, Catherine A. Aytaman, Ayse Llovet, Josep M. Brown, Sheldon T. Bini, Edmund J. CA North Amer Liver Canc HIV Study TI Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: A US-Canadian multicenter study SO JOURNAL OF HEPATOLOGY LA English DT Article DE hepatocellular carcinoma; HIV; hepatitis C; hepatitis B; treatment ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; STAGING-SYSTEM; UNITED-STATES; ANTIRETROVIRAL THERAPY; PROSPECTIVE VALIDATION; FIBROSIS PROGRESSION; PROGNOSTIC FEATURES; COINFECTED PATIENTS; NATURAL-HISTORY AB Background/Aims: HIV-infected patients now live longer and often have complications of liver disease, especially with hepatitis B or C virus coinfection. Limited data are available on those with hepatocellular carcinoma (HCC). Methods:A retrospective analysis from 1992 to 2005 in 6 centers identified 63 HIV-infected HCC patients. Controls were 226 consecutive HIV-negative HCC patients from four sites. Results: HIV-positive patients were younger than controls (52 vs. 64 years, p < 0.001), more commonly had chronic hepatitis B or C (97% vs. 73%, p < 0.001), were more frequently symptomatic (51% vs. 38%, p = 0.048), had a higher median alfa-fetoprotein level (227 vs. 51 ng/ml, p = 0.005), but a similar mean Child-Turcotte-Pugh score (7.0 vs. 7.5, p = 0.05) and HCC staging score (Barcelona-Clinic-Liver-Cancer stages C + D in 50% vs. 58%, p = 0.24). HCC developed faster in HIV/HCV-coinfected than in HCV-monoinfected patients (mean, 26 vs. 34 years after HCV infection, p = 0.002). HIV-positive patients received proven therapy more often (48% vs. 31%, p = 0.017), but median survival was similar (6.9 vs. 7.5 months, p = 0.44). Independent factors predicting survival were symptomatic presentation (hazard ratio [HR], 0.437; p < 0.001), any proven therapy (HR, 2.19; p < 0.001), diagnosis after 01-Jan-2002 (HR, 1.52; p = 0.010), Barcelona-Clinic-Liver-Cancer stages C + D (HR, 0.491; p < 0.001), AST/ALT >= 2.00 (HR, 0.597; p = 0.001), AFP >= 400 ng/mL (HR, 0.55, p = 0.003), and platelets >= 100,000/mm(3) (HR, 0.651; p = 0.012), but not HIV-serostatus (p = 0.19). In HIV-infected patients without HCC therapy (n = 33), median survival was longer with undetectable HIV RNA (<400 copies/mL) than with HIV viremia (6.5 vs. 2.6 months, p = 0.013). Conclusions: HIV-positive HCC patients are younger and more frequently symptomatic and infected with HCV or HBV than HIV-negative patients. Tumor staging and survival are similar. In untreated patients, undetectable HIV RNA independently predicts better survival. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 Mt Sinai Sch Med, Bronx Vet Affairs Med Ctr, Div Infect Dis & Liver Dis, New York, NY 10029 USA. Mt Sinai Sch Med, Div Infect Dis, New York, NY USA. Mt Sinai Sch Med, Div Liver Dis, New York, NY USA. Univ Calif San Francisco, VA Med Ctr, Sch Med, San Francisco, CA USA. Cornell Univ, Presbyterian Hosp, Weill Coll Med, New York, NY USA. Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. Univ Turin, Toronto Gen Hosp, Sch Med, Toronto, ON, Canada. Johns Hopkins Sch Med, Baltimore, MD USA. Yale Univ, VA Med Ctr, Sch Med, New Haven, CT USA. Univ Texas, SW Med Ctr, Dallas, TX USA. VA Med Ctr, Salisbury, NC USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Calif Pacific Med Ctr, San Francisco, CA USA. SUNY Downstate Hlth Sci Ctr, VA New York Harbor Hlth Care Syst, Brooklyn, NY USA. NYU, Sch Med, VA New York Harbor Hlth Care Syst, New York, NY USA. RP Brau, N (reprint author), Mt Sinai Sch Med, Bronx Vet Affairs Med Ctr, Div Infect Dis & Liver Dis, New York, NY 10029 USA. EM norbert.brau@va.gov RI Llovet, Josep M /D-4340-2014 OI Llovet, Josep M /0000-0003-0547-2667 NR 36 TC 125 Z9 130 U1 0 U2 0 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 2007 VL 47 IS 4 BP 527 EP 537 DI 10.1016/j.jhep.2007.06.010 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 218OQ UT WOS:000250025200016 PM 17692986 ER PT J AU Balas, B Belfort, R Harrison, SA Darland, C Finch, J Schenker, S Gastaldelli, A Cusi, K AF Balas, Bogdan Belfort, Renata Harrison, Stephen A. Darland, Celia Finch, Joan Schenker, Steven Gastaldelli, Amalia Cusi, Kenneth TI Pioglitazone treatment increases whole body fat but not total body water in patients with non-alcoholic steatohepatitis SO JOURNAL OF HEPATOLOGY LA English DT Article DE non-alcoholic steatohepatitis (NASH); pioglitazone; total body fat; total body water ID RANDOMIZED CONTROLLED-TRIAL; CONGESTIVE-HEART-FAILURE; PLACEBO-CONTROLLED TRIAL; TYPE-2 DIABETIC-PATIENTS; INSULIN SENSITIVITY; BIOELECTRICAL-IMPEDANCE; GLYCEMIC CONTROL; ENERGY-EXPENDITURE; METFORMIN; THIAZOLIDINEDIONES AB Background/Aims: Non-Alcoholic Steatohepatitis (NASH) is a chronic liver disease frequently associated with insulin resistance and type 2 diabetes mellitus (T2DM). Pioglitazone reverses the metabolic and histological abnormalities of patients with impaired glucose tolerance or T2DM and NASH, but also leads to weight gain. To understand the nature of weight gain associated with pioglitazone treatment in NASH we analyzed 35 patients who completed tests for determination of whole body fat (WBF) and total body water (TBW). Methods: Twenty-one patients received pioglitazone and 14 placebo in a double-blind, randomized fashion for a period of 6 months. WBF and TBW were measured before and after treatment using DXA, a water dilution technique and bioimpedance. Results: Pioglitazone increased body weight (from 93.6 +/- 4.2 to 96.1 +/- 4.5 kg, p < 0.003) and WBF measured with DXA (from 32.9 +/- 2.1 to 35.4 +/- 2.5 kg, p < 0.002) while no changes were seen with placebo. Total body water was not altered significantly either after pioglitazone (from 45.4 +/- 2.3 to 45.6 +/- 2.7 1, p = NS) or placebo. Muscle hydration and extracellular water were unchanged both by pioglitazone and placebo treatments. Conclusions: Six months of pioglitazone treatment in patients with NASH is associated with weight gain that is attributable to an increase in adipose tissue mass and not to water retention. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Diabet Div, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Gastroenterol, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, Diabet Div, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, Div Nutr, San Antonio, TX USA. Brooke Army Med Ctr, Div Gastroenterol, Houston, TX USA. CNR, Inst Clin Physiol, Pisa, Italy. RP Cusi, K (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Diabet Div, Room 3 308S,7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM cusi@uthscsa.edu RI Gastaldelli, Amalia/H-3319-2014 OI Gastaldelli, Amalia/0000-0003-2594-1651 FU NCRR NIH HHS [M01-RR-01346] NR 50 TC 41 Z9 41 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 2007 VL 47 IS 4 BP 565 EP 570 DI 10.1016/j.jhep.2007.04.013 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 218OQ UT WOS:000250025200020 PM 17560678 ER PT J AU Colmenero, P Zhang, AL Qian, T Lu, L Cantor, H Soderstrom, K AF Colmenero, Paula Zhang, Angela L. Qian, Ting Lu, Linrong Cantor, Harvey Soederstroem, Kalle TI Qa-1(b)-Dependent modulation cross-talk in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; DENDRITIC CELLS; NK CELLS; LYMPH-NODES; IFN-GAMMA; T-CELLS; ANTIVIRAL IMMUNITY; MOLECULE QA-1(B); RECEPTORS; RESPONSES AB Dendritic cells (DC) trigger activation and IFN-gamma release by NK cells in lymphoid tissues, a process important for the polarization of Th1 responses. Little is known about the molecular signals that regulate DC-induced NK cell IFN-gamma synthesis. In this study, we analyzed whether the interaction between Qa-1(b) expressed on DC and its CD94/NKG2A receptor on NK cells affects this process. Activation of DC using CpG-oligodeoxynucleotides in Qa-1(b)-deficient mice, or transfer of CpG-oligodeoxynucleotide-activated Qa-1(b)-deficient DC into wild-type mice, resulted in dramatically increased IFN-,y production by NK cells, as, compared with that induced by Qa-1(b)-expressing DC. Masking the CD94/NKG2A inhibitory receptor on NK cells in wild-type mice similarly enhanced the IFN-gamma response of these cells to Qa-1(b) expressing DC. Furthermore, NK cells from CD94/NKG2A-deficient mice displayed higher IFN-gamma production upon DC stimulation. These results demonstrate that Qa-1(b) is critically involved in regulating IFN-gamma synthesis by NK cells in vivo through its interaction with CD94/NKG2A inhibitory receptors. This receptor-ligand interaction may be essential to prevent unabated cytokine production by NK cells during an inflammatory response. C1 Stanford Univ, Stanford Blood Ctr, Dept Pathol, Sch Med, Palo Alto, CA 94304 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Colmenero, P (reprint author), Stanford Univ, Stanford Blood Ctr, Dept Pathol, Sch Med, 3373 Hillview Ave, Palo Alto, CA 94304 USA. EM paucol@stanford.edu RI Soderstrom, Kalle/G-5788-2011; Lu, Linrong/A-1429-2013 FU NHLBI NIH HHS [HL57443]; NIAID NIH HHS [AI055468]; NIAMS NIH HHS [AR051748] NR 36 TC 8 Z9 8 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2007 VL 179 IS 7 BP 4608 EP 4615 PG 8 WC Immunology SC Immunology GA 214QB UT WOS:000249752100037 PM 17878358 ER PT J AU Weng, MQ Huntley, D Huang, IF Foye-Jackson, O Wang, LJ Sarkissian, A Zhou, QP Walker, WA Cherayil, BJ Shi, HN AF Weng, Meiqian Huntley, Deke Huang, I-Fei Foye-Jackson, Ondulla Wang, Lijian Sarkissian, Aliese Zhou, Qingping Walker, W. Allan Cherayil, Bobby J. Shi, Hai Ning TI Alternatively activated macrophages in intestinal helminth infection: effects on concurrent bacterial colitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; MURINE COLONIC HYPERPLASIA; CITROBACTER-RODENTIUM; T-CELL; SCHISTOSOMA-MANSONI; DENDRITIC CELLS; TRICHURIS-SUIS; MICE; RESPONSES; NEMATODE AB The distribution of several pathogenic helminth infections coincides geographically with many devastating microbial diseases, including enteric bacterial infections. To dissect the mechanisms by which helminths modulate the host's response to enteric bacteria and bacteria-mediated intestinal inflammation, we have recently established A coinfection model and shown that coinfection with the helminth Heligniosomoides polygyrus exacerbates colitis induced by infection with the Gram-negative bacterial pathogen Citrobacter rodentium. The disease severity of the coinfected mice was correlated With high Citrobacter loads in the gut, translocation of the bacteria into mucosal and systemic immune compartments, delayed bacterial clearance, and a significantly enhanced colonic TNF-alpha response. In the present study, using our in vivo coinfection model as well as in vitro approaches, we test the hypothesis that the phenotypic and functional alterations in macrophages induced by the helminth-driven T cell response may contribute to the observed alterations in the response to C rodentium. We show that via a STAT6-dependent mechanism H. polygyrus coinfection results in a marked infiltration into the colonic lamina propria of F4/80(+) cells that have the phenotype of alternatively activated macrophages. Functional analysis of these macrophages further shows that they are impaired in their killing of internalized bacteria. Yet, these cells produce an enhanced amount of TNF-a in response to C rodentium infection. These results demonstrate that helminth infection can impair host protection against concurrent enteric bacterial infection and promote bacteria-induced intestinal injury through a mechanism that involves the induction of alternatively activated macrophages. C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. 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 FIC NIH HHS [TW001265, D43 TW001265]; NICHD NIH HHS [5 T32 HD052961, T32 HD052961]; NIDDK NIH HHS [K01 DK059996, P30 DK 40561, P30 DK040561, P30 DK040561-12] NR 43 TC 60 Z9 62 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2007 VL 179 IS 7 BP 4721 EP 4731 PG 11 WC Immunology SC Immunology GA 214QB UT WOS:000249752100050 PM 17878371 ER PT J AU Avigan, DE Vasir, B George, DJ Oh, WK Atkins, MB McDermott, DF Kantoff, PW Figlin, RA Vasconcelles, MJ Xu, Y Kufe, D Bukowski, RM AF Avigan, David E. Vasir, Baldev George, Daniel J. Oh, William K. Atkins, Michael B. McDermott, David F. Kantoff, Philip W. Figlin, Robert A. Vasconcelles, Michael J. Xu, Yuanxin Kufe, Donald Bukowski, Ronald M. TI Phase I/II study of vaccination with electrofused allogeneic dendritic Cells/Autologous tumor-derived cells in patients with stage IV renal cell carcinoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE tumor immunotherapy; dendritic cell tumor fusion; renal cell carcinoma ID THERAPEUTIC ANTITUMOR IMMUNITY; IN-VITRO; MULTIPLE-MYELOMA; T-CELL; METASTATIC MELANOMA; CLINICAL-RESPONSES; GLIOMA PATIENTS; CANCER-IMMUNOTHERAPY; ANTIGEN; FUSIONS AB In the present study, we assessed the feasibility, toxicity, immunologic response, and clinical efficacy of vaccination with allogeneic dendritic cell (DC)/tumor fusions in patients with metastatic renal cell carcinoma (RCC). Patients with stage IV RCC with accessible tumor lesions or independent therapeutic indications for nephrectomy were eligible for enrollment. Tumors were processed into single cell suspensions and cryopreserved. DCs were generated from adherent peripheral blood mononuclear cells isolated from normal volunteers and cultured with granulocyte macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha. DCs were fused to patient derived RCC with serial electrical pulses. Patients received up to 3 vaccinations at a fixed dose of 4 x 10(7) to 1 x 10(8) cells administered at 6-week intervals. Twenty-four patients underwent vaccination. Twenty-one and 20 patients were evaluable for immunologic and clinical response, respectively. DCs demonstrated a characteristic phenotype with prominent expression of HLA class II and costimulatory molecules. A mean fusion efficiency of 20% was observed, determined by the percent of cells coexpressing DC and tumor antigens. No evidence of significant treatment related toxicity or auto-immunity was observed. Vaccination resulted in antitumor immune responses in 10/21 evaluable patients as manifested by an increase in CD4 and/or CD8(+) T-cell expression of interferon-gamma after ex vivo exposure to tumor lysate. Two patients demonstrated a partial clinical response by Response Evaluation Criteria in Solid Tumors criteria and 8 patients had stabilization of their disease. Vaccination of patients with RCC with allogeneic DC/tumor fusions was feasible, well tolerated, and resulted in immunologic and clinical responses in a subset of patients. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Genzyme Corp, Cambridge, MA USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Avigan, DE (reprint author), Beth Israel Deaconess Med Ctr, Kirstein Rm 13,330 Brookline Ave, Boston, MA 02215 USA. EM davigan@bidmc.barvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 53 TC 77 Z9 87 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2007 VL 30 IS 7 BP 749 EP 761 PG 13 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 215GE UT WOS:000249795500008 PM 17893567 ER PT J AU Tsao, H Florez, JC AF Tsao, Hensin Florez, Jose C. TI Introduction to genetic association studies SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; RISK LOCI; EPIDEMIOLOGY; REPLICATION C1 Massachusetts Gen Hosp, Wellman Ctr, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Boston, MA 02115 USA. MIT, Broad Inst, Program Med & Populat Genet, Boston, MA USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Wellman Ctr, Dept Dermatol, Bartlett Hall 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org NR 14 TC 6 Z9 6 U1 0 U2 3 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 2007 VL 127 IS 10 BP 2283 EP 2287 DI 10.1038/sj.jid.5701054 PG 5 WC Dermatology SC Dermatology GA 217FF UT WOS:000249933100001 PM 17853910 ER PT J AU Dellavalle, RP Schilling, LM Rodriguez, MA Van de Sompel, H Bollen, J AF Dellavalle, R. P. Schilling, L. M. Rodriguez, M. A. Van de Sompel, H. Bollen, J. TI The effect of PageRank adjustment on dermatology journal impact factor SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 05-08, 2007 CL Zurich, SWITZERLAND SP European Soc Dermatol Res C1 [Dellavalle, R. P.] Denver VA Med Ctr, Denver, CO USA. [Schilling, L. M.] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Rodriguez, M. A.; Van de Sompel, H.; Bollen, J.] Los Alamos Natl Lab, Los Alamos, NM USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2007 VL 127 SU 2 BP S27 EP S27 PG 1 WC Dermatology SC Dermatology GA 217FI UT WOS:000249933400163 ER PT J AU Hoek, KS Lin, WM Schlegel, NC Mnich, C Kobert, N Storz, M Mihic, D Moch, H Garraway, LA Dummer, R AF Hoek, K. S. Lin, W. M. Schlegel, N. C. Mnich, C. Kobert, N. Storz, M. Mihic, D. Moch, H. Garraway, L. A. Dummer, R. TI Prognostic loss of heterozygosity patterns in melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 05-08, 2007 CL Zurich, SWITZERLAND SP European Soc Dermatol Res C1 [Hoek, K. S.; Schlegel, N. C.; Mnich, C.; Kobert, N.; Storz, M.; Mihic, D.; Moch, H.; Dummer, R.] Univ Zurich Hosp, Zurich, Switzerland. [Lin, W. M.] Broad Inst, Cambridge, MA USA. [Garraway, L. A.] Dana Farber Canc Inst, Boston, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2007 VL 127 SU 2 BP S52 EP S52 PG 1 WC Dermatology SC Dermatology GA 217FI UT WOS:000249933400310 ER PT J AU Stewart, CR Haw, A Lopez, R McDonald, TO Callaghan, JM McConville, MJ Moore, KJ Howlett, GJ O'Brien, KD AF Stewart, Cameron R. Haw, Antonio, III Lopez, Roland McDonald, Thomas O. Callaghan, Judy M. McConville, Malcolm J. Moore, Kathryn J. Howlett, Geoffrey J. O'Brien, Kevin D. TI Serum amyloid P colocalizes with apolipoproteins in human atheroma: functional implications SO JOURNAL OF LIPID RESEARCH LA English DT Article DE atherosclerosis; macrophage; immunohistochemistry; amyloid ID CORONARY ATHEROSCLEROTIC PLAQUES; C-II; A-I; LIPOPROTEIN-LIPASE; ALZHEIMER-DISEASE; MURINE MODELS; COMPONENT; FIBRILS; BETA; PROTEIN AB Serum amyloid P (SAP) is a common component of human amyloid deposits and has been identified in atherosclerotic lesions. We investigated the extent of the colocalization of SAP with apolipoprotein A-I (apoA-I), apoB, apoC-II, and apoE in human coronary arteries and explored potential roles for SAP in these regions, specifically the effect of SAP on the rate of formation and macrophage recognition of amyloid fibrils composed of apoC-II. Analysis of 42 human arterial sections by immunohistochemistry and double label fluorescence microscopy demonstrated that SAP and apoA-I, apoB, apoC-II, and apoE were increased significantly in atherosclerotic lesions compared with nonatherosclerotic segments. SAP colocalized with all four apolipoproteins to a similar extent, whereas plaque macrophages were found to correlate most strongly with apoC-II and apoB. In vitro studies showed that SAP accelerated the formation of amyloid fibrils by purified apoC-II. Furthermore, SAP strongly inhibited the phagocytosis of apoC-II amyloid fibrils by primary macrophages and macrophage cell lines and blocked the resultant production of reactive oxygen species. The ability of SAP to accelerate apoC-II amyloid fibril formation and inhibit macrophage recognition of apoC-II fibrils suggests that SAP may modulate the inflammatory response to amyloid fibrils in atherosclerosis. C1 Univ Melbourne, Dept Biochem & Mol Biol, Bio21 Mol Sci & Biotechnol Inst, Parkville, Vic 3010, Australia. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. RP Howlett, GJ (reprint author), Univ Melbourne, Dept Biochem & Mol Biol, Bio21 Mol Sci & Biotechnol Inst, Parkville, Vic 3010, Australia. EM ghowlett@unimelb.edu.au RI Stewart, Cameron/E-6823-2011; OI Moore, kathryn/0000-0003-2505-2547 NR 47 TC 37 Z9 39 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD OCT PY 2007 VL 48 IS 10 BP 2162 EP 2171 DI 10.1194/jlr.M700098-JLR200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 211FK UT WOS:000249509500007 PM 17630380 ER PT J AU Liu, YT D'Arceuil, H He, JL Duggan, M Gonzalez, G Pryor, J de Crespigny, A AF Liu, Yutong D'Arceuil, Helen He, Julian Duggan, Mike Gonzalez, Gilberto Pryor, Johnny de Crespigny, Alex TI MRI of spontaneous fluctuations after acute cerebral ischemia in nonhuman primates SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE stroke; MRI; spontaneous fluctuations; vasomotion ID BOLD SIGNAL; CEREBROVASCULAR REACTIVITY; VASOMOTION; BRAIN; OCCLUSION; CORTEX; FMRI; RAT AB Purpose: To study the spontaneous low-frequency blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal fluctuations during hyperacute focal cerebral ischemia. Materials and Methods: A stroke model in nonhuman primates (macaques) was used in this study. Spontaneous fluctuations were recorded using a series of gradient-recalled echo (GRE) echo-planar imaging (EPI) images. Fast Fourier transformation (FIT) was performed on the serial EPI data to calculate the frequency and magnitude of the spontaneous fluctuations. Diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) were preformed to detect the ischemic lesion. Results: The frequency of these fluctuations decreased in the pedinfarct tissue in the ipsilateral hemisphere, while their magnitude increased. This area of abnormal signal fluctuations often extended beyond the hyperacute diffusion/perfusion abnormality. Conclusion: This study suggests that measurement of the spontaneous fMRI signal fluctuations provides different information than is available from diffusion/perfusion or T2-weighted MRI. C1 Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. RP de Crespigny, A (reprint author), MGH NMR Ctr Martinos Ctr, Dept Radiol, Rm 2301,Bldg 149,13th St, Hillsborough 02129, North Ireland. EM alexdec@nmr.mgh.harvard.edu FU NINDS NIH HHS [1R01-NS41285] NR 19 TC 12 Z9 15 U1 1 U2 3 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 2007 VL 26 IS 4 BP 1112 EP 1116 DI 10.1002/jmri.21131 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216SH UT WOS:000249898800037 PM 17896395 ER PT J AU Atlas, SA AF Atlas, Steven A. TI The renin-angiotensin aldosterone system: Pathophysiological role and pharmacologic inhibition SO JOURNAL OF MANAGED CARE PHARMACY LA English DT Article DE renin-angiotensin aldosterone system; hypertension; angiotensin II; renin; ACE inhibitors; angiotensin receptor blockers ID ACUTE MYOCARDIAL-INFARCTION; CONVERTING ENZYME-INHIBITORS; LEFT-VENTRICULAR DYSFUNCTION; CORONARY-ARTERY-DISEASE; CHRONIC HEART-FAILURE; HIGH-RISK PATIENTS; ESSENTIAL-HYPERTENSION; RANDOMIZED-TRIAL; CARDIOVASCULAR MORBIDITY; TREATING HYPERTENSION AB BACKGROUND: The renin-angiotensin aldosterone system (RAAS) is a hormonal cascade that functions in the homeostatic control of arterial pressure, tissue perfusion, and extracellular volume. Dysregulation of the RAAS plays an important role in the pathogenesis of cardiovascular and renal disorders. OBJECTIVES: To review the role of the RAAS in the development of hypertensive cardiovascular disease and related conditions and provide an overview of the classes of pharmacologic agents that inhibit this system. RESULTS: The RAAS is initiated by the regulated secretion of renin, the rate-limiting enzyme that catalyzes the hydrolysis of angiotensin (Ang) I from the N-terminus of angiotensinogen. Ang I is in turn hydrolyzed by angiotensin-converting enzyme (ACE) to form Ang II, a potent vasoconstrictor and the primary active product of the RAAS. Recent evidence has suggested that other metabolites of Ang I and II may have biological activity, particularly in tissues. Development of agents that block the RAAS (e.g., beta blockers, ACE inhibitors [ACEIs], and angiotensin receptor blockers [ARBs]) began as a therapeutic strategy to treat hypertension. Preclinical and clinical studies have indicated important additional cardiovascular and renal therapeutic benefits of ACEIs and ARBs. However, blockade of the RAAS with these agents is incomplete. CONCLUSION: Therapeutic approaches that target more complete inhibition of the RAAS may offer additional clinical benefits for patients with cardiovascular and renal disorders. These approaches may include dual blockade using ACEIs and ARBs in combination, or new therapeutic modalities such as direct renin inhibition with aliskiren, recently approved for the treatment of hypertension. C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. James J Peters VA Med Ctr, Hypertens Res Lab, Bronx, NY USA. RP Atlas, SA (reprint author), 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM steven.atlas@med.va.gov NR 61 TC 75 Z9 78 U1 2 U2 27 PU ACAD MANAGED CARE PHARMACY PI ALEXANDRIA PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA SN 1083-4087 J9 J MANAGE CARE PHARM JI J. Manag. Care Pharm. PD OCT PY 2007 VL 13 IS 8 SU B BP S9 EP S20 PG 12 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 228UB UT WOS:000250757000002 ER PT J AU Blondeau, N Lai, YS Tyndall, S Popolo, M Topalkara, K Pru, JK Zhang, L Kim, H Liao, JK Ding, K Waeber, C AF Blondeau, Nicolas Lai, Yushuan Tyndall, Sarah Popolo, Margherita Topalkara, Kamil Pru, James K. Zhang, Ling Kim, HyungHwan Liao, James K. Ding, Kan Waeber, Christian TI Distribution of sphingosine kinase activity and mRNA in rodent brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cerebral ischemia; glial cells; neurons; sphingolipid metabolism; sphingosine-1-phosphate ID TUMOR-NECROSIS-FACTOR; FACTOR-INDUCED ACTIVATION; PROGRAMMED CELL-DEATH; GROWTH-FACTOR; NEURITE RETRACTION; ENDOTHELIAL-CELLS; SURFACE RECEPTOR; GLIOMA-CELLS; PC12 CELLS; 1-PHOSPHATE AB Sphingosine-1 -phosphate (S1 P) is a lipid mediator that exerts multiple cellular functions through activation of a subfamily of G-protein-coupled receptors. Although there is evidence that S1P plays a role in the developing and adult CNS, little is known about the ability of brain parenchyma to synthesize this lipid. We have therefore analyzed the brain distribution of the enzymatic activity of the S1 P synthesizing enzyme, sphingosine kinase (SPHK) [EC:2.7.1.91], as well as mRNA distribution for one of the two isoforms of this enzyme, sphingosine kinase 2. SPHK activity, measured by the conversion of [H-3]sphingosine to [H-3]S1P, is highest in cerebellum, followed by cortex and brainstem. Lowest activities were found in striatum and hippocampus. Sensitivity to 0. 1 % Triton-X suggests that this activity is accounted for by SPHK2. RT-PCR and in situ hybridization studies show that mRNA for this isoform has a distribution similar to that of SPHK activity. In vivo and in vitro ischemia increase SPHK activity and SPHK2 mRNA levels. These results indicate that SPHK2 is the predominant S1P-synthesizing isoform in normal brain parenchyma. Its heterogeneous distribution, in particular laminar distribution in cortex, suggests a neuronal localization and a possible role in cortical and cerebellar functions, in normal as well as ischemic brain. C1 Massachusetts Gen Hosp, Dept Radiol, Stroke Neurovasc Regulat Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Charlestown, MA USA. Brigham & Womens Hosp, Harvard Med Sch, Vasc Med Res, Cambridge, MA USA. RP Waeber, C (reprint author), CNRS, UNSA, UMR 6097, Inst Pharmacol Mol & Cellulaire, Sophia Antipolis, F-06560 Valbonne, France. EM waeber@helix.mgh.harvard.edu RI Waeber, Christian/A-8333-2009; Blondeau, Nicolas/M-5002-2016 OI Waeber, Christian/0000-0001-6078-0027; Blondeau, Nicolas/0000-0001-5954-4094 FU NHLBI NIH HHS [R01 HL052233-11, R01 HL080187-03, R01 HL052233, R01 HL070274-05, R01 HL080187, R01 HL052233-12, R01 HL070274, R01 HL070274-04, R01 HL080187-01A1, R01 HL080187-02]; NIDDK NIH HHS [R01 DK062729-05, R01 DK062729, R01 DK062729-04]; NINDS NIH HHS [NS049263, R01 NS049263, NS052195, P01 NS010828, P01 NS010828-330036, R21 NS052195] NR 50 TC 49 Z9 49 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2007 VL 103 IS 2 BP 509 EP 517 DI 10.1111/j.1471-4159.2007.04755.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 223PN UT WOS:000250384500008 PM 17623044 ER PT J AU Brickell, KL Leverenz, JB Steinbart, EJ Rumbaugh, M Schellenberg, GD Nochlin, D Lampe, TH Holm, IE Van Deerlin, V Yuan, WX Bird, TD AF Brickell, Kiri L. Leverenz, James B. Steinbart, Ellen J. Rumbaugh, Malia Schellenberg, Gerard D. Nochlin, David Lampe, Thomas H. Holm, Ida E. Van Deerlin, Vivianna Yuan, Wuxing Bird, Thomas D. TI Clinicopathological concordance and discordance in three monozygotic twin pairs with familial Alzheimer's disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID APOLIPOPROTEIN-E; LEWY BODIES; ONSET; MUTATIONS; DEMENTIA; GENE; CONSORTIUM; DIAGNOSIS; PATHOLOGY; SERIES AB Aim: Neuropathological examination of both individuals in a monozygotic ( MZ) twin pair with Alzheimer's disease ( AD) is rare, especially in the molecular genetic era. We had the opportunity to assess the concordance and discordance of clinical presentation and neuropathology in three MZ twin pairs with AD. Methods: The MZ twins were identified and characterised by the University of Washington Alzheimer's Disease Research Center. We reviewed the available clinical and neuropathological records for all six cases looking specifically for concordance and discordance of clinical phenotype, neuritic amyloid plaques ( NP), neurofibrillary tangles ( NFT) and Lewy related pathology ( LRP). Results: Discordance in age of onset for developing AD in the MZ twins varied from 4 to 18 years. Clinical presentations also differed between twins. One twin presented with a dementia with Lewy Body clinical syndrome while the other presented with typical clinical AD. Neuropathology within the MZ twin pairs was concordant for NP and NFT, regardless of duration of disease, and was discordant for LRP. This difference was most marked in the late onset AD twin pair. One pair was found to have a mutation in presenilin- 1 ( PS1) ( A79V) with remarkably late onset in a family member. Conclusions: MZ twins with AD can vary considerably in age of onset, presentation and disease duration. The concordance of NP and NFT pathological change and the discordance of LRP support the concept that, in AD, the former are primarily under genetic control whereas the latter ( LRP) is more influenced by disease duration and environmental factors. The A79V mutation in PS1 can be associated with very late onset of dementia. C1 GRECC, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Bird, TD (reprint author), GRECC, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM tomnroz@u.washington.edu FU NIA NIH HHS [P01 AG017586, P50 AG005136, P50 AG 005136-22, AG17586] NR 30 TC 31 Z9 33 U1 0 U2 5 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 PY 2007 VL 78 IS 10 BP 1050 EP 1055 DI 10.1136/jnnp.2006.113803 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 211LB UT WOS:000249524200005 PM 17615170 ER PT J AU Seshagiri, CV Delgutte, B AF Seshagiri, Chandran V. Delgutte, Bertrand TI Response properties of neighboring neurons in the auditory midbrain for pure-tone stimulation: A tetrode study SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID DORSAL COCHLEAR NUCLEUS; INTERAURAL TIME DIFFERENCES; SUPERIOR OLIVARY NUCLEUS; INFERIOR COLLICULUS; SINGLE-UNIT; BINAURAL INTERACTION; CHANGING FREQUENCY; SOUND LOCALIZATION; DECEREBRATE CATS; CELL-TYPES AB The complex anatomical structure of the central nucleus of the inferior colliculus (ICC), the principal auditory nucleus in the midbrain, may provide the basis for functional organization of auditory information. To investigate this organization, we used tetrodes to record from neighboring neurons in the ICC of anesthetized cats and studied the similarity and difference among the responses of these neurons to pure-tone stimuli using widely used physiological characterizations. Consistent with the tonotopic arrangement of neurons in the ICC and reports of a threshold map, we found a high degree of correlation in the best frequencies (BFs) of neighboring neurons, which were mostly <3 kHz in our sample, and the pure-tone thresholds among neighboring neurons. However, width of frequency tuning, shapes of the frequency response areas, and temporal discharge patterns showed little or no correlation among neighboring neurons. Because the BF and threshold are measured at levels near the threshold and the characteristic frequency (CF), neighboring neurons may receive similar primary inputs tuned to their CF; however, at higher levels, additional inputs from other frequency channels may be recruited, introducing greater variability in the responses. There was also no correlation among neighboring neurons' sensitivity to interaural time differences (ITD) measured with binaural beats. However, the characteristic phases (CPs) of neighboring neurons revealed a significant correlation. Because the CP is related to the neural mechanisms generating the ITD sensitivity, this result is consistent with segregation of inputs to the ICC from the lateral and medial superior olives. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Delgutte, B (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Bertrand_Delgutte@meei.harvard.edu OI , /0000-0003-1349-9608 FU NIDCD NIH HHS [P30 DC005209, P30 DC005209-019001, R01 DC002258, R01 DC002258-13, T32 DC000038, T32 DC00038] NR 51 TC 17 Z9 17 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2007 VL 98 IS 4 BP 2058 EP 2073 DI 10.1152/jn.01317.2006 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 219KE UT WOS:000250082700021 PM 17671101 ER PT J AU Srinivasan, L Eden, UT Mitter, SK Brown, EN AF Srinivasan, Lakshminarayan Eden, Uri T. Mitter, Sanjoy K. Brown, Emery N. TI General-purpose filter design for neural prosthetic devices SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID BRAIN-MACHINE INTERFACES; GOAL-DIRECTED MOVEMENTS; COMPUTER INTERFACE; CORTICAL-NEURONS; CONTROL SIGNALS; KALMAN FILTER; MOTOR; MODEL; ENSEMBLE; CORTEX AB Brain-driven interfaces depend on estimation procedures to convert neural signals to inputs for prosthetic devices that can assist individuals with severe motor deficits. Previous estimation procedures were developed on an application-specific basis. Here we report a coherent estimation framework that unifies these procedures and motivates new applications of prosthetic devices driven by action potentials, local field potentials (LFPs), electrocorticography (ECoG), electroencephalography ( EEG), electromyography (EMG), or optical methods. The brain-driven interface is described as a probabilistic relationship between neural activity and components of a prosthetic device that may take on discrete or continuous values. A new estimation procedure is developed for action potentials, and a corresponding procedure is described for field potentials and optical measurements. We test our framework against dominant approaches in an arm reaching task using simulated traces of ensemble spiking activity from primary motor cortex (MI) and a wheelchair navigation task using simulated traces of EEG-band power. Adaptive filtering is incorporated to demonstrate performance under neuron death and discovery. Finally, we characterize performance under model misspecification using physiologically realistic history dependence in MI spiking. These simulated results predict that the unified framework outperforms previous approaches under various conditions, in the control of position and velocity, based on trajectory and endpoint mean squared errors. C1 Massachusetts Gen Hosp, Ctr Nervous Syst Repair, Dept Neurosurg, Boston, MA 02114 USA. MIT, Dept Elect Engn & Comp Sci, Informat & Decis Syst Lab, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Charlestown, MA USA. RP Srinivasan, L (reprint author), Massachusetts Gen Hosp, Ctr Nervous Syst Repair, Dept Neurosurg, 50 Blossom St,EDR-410, Boston, MA 02114 USA. EM lsrinivasan@partners.org FU NIDA NIH HHS [R01 DA015644]; NIGMS NIH HHS [T32 GM07753-28, T32 GM007753] NR 73 TC 61 Z9 61 U1 1 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2007 VL 98 IS 4 BP 2456 EP 2475 DI 10.1152/jn.01118.2006 PG 20 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 219KE UT WOS:000250082700054 PM 17522167 ER PT J AU Driscoll, WD Columbia, MA Peterfreund, RA AF Driscoll, William D. Columbia, Mary Ann Peterfreund, Robert A. TI Awareness during general anesthesia: Analysis of contributing causes aided by automatic data capture SO JOURNAL OF NEUROSURGICAL ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Neurosurgical-Anesthesia-and-Critical-Care CY 2006 CL Chicago, IL SP Soc Neurosurg Anesthesia Crit Care DE awareness; anesthesia information management systems; general anesthesia AB The cause of the awareness under general anesthesia often cannot be definitely determined from retrospective reviews of handwritten records, examinations of equipment, or interviews with clinicians. Failure to deliver the intended concentrations of anesthetic agents to the patient is one possible contributing cause for awareness. An advantage of an automated Anesthesia Information Management System (AIMS) is its ability to electronically capture and preserve case data that might otherwise be lost. We reviewed the AIMS records of 3 anesthetics in which intraoperative awareness was felt to have probably occurred. The details of the reported awareness event were temporally correlated with the anesthetic gas concentrations in an effort to determine if low concentrations were contributing factors. The data captured by the AIMS revealed low levels of inspired or expired inhalation agents during the intervals correlating with apparent patient recall. The findings suggest that failure to deliver sufficient concentrations of anesthetic gases permitted awareness events in these cases. Thus data from automated anesthesia information management in the operating room may help identify causes of awareness, and means to prevent awareness can be instituted. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Peterfreund, RA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Jackson 439,55 Fruit St, Boston, MA 02114 USA. EM RPeterfreund@partners.org NR 11 TC 5 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0898-4921 J9 J NEUROSURG ANESTH JI J. Neurosurg. Anesthesiol. PD OCT PY 2007 VL 19 IS 4 BP 268 EP 272 DI 10.1097/ANA.0b013e318139f7df PG 5 WC Anesthesiology; Clinical Neurology; Surgery SC Anesthesiology; Neurosciences & Neurology; Surgery GA 213ZL UT WOS:000249705700010 PM 17893580 ER PT J AU Valente, S Murray, L Fisher, D AF Valente, Sharon Murray, Lillian Fisher, Diane TI Nurses improve medication safety with medication allergy and adverse drug reports SO JOURNAL OF NURSING CARE QUALITY LA English DT Article DE adverse drug reactions; documentation; medication allergy; medication safety AB Medicine-related illnesses cost more than $75 billion annually, Adverse drug reactions (ADRs) are the fourth to sixth leading causes of death in the United States. An educational campaign to reduce ADRs and improve documentation included (1) an allergy awareness campaign, (2) staff nurses' training on documentation of allergies/ADRs, (3) patient-oriented brochures to encourage allergy reporting and ADRs, and (4) a fact sheet about ADRs. As a result, the documentation of medication allergies and ADRs improved significantly in our organization. C1 Vet Affairs Greater Losangeles Hearthcare Syst, Los Angeles, CA USA. RP Valente, S (reprint author), 346 N Bowling Green Way, Los Angeles, CA 90073 USA. EM sharon.valente@va.gov NR 9 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-3631 J9 J NURS CARE QUAL JI J. Nurs. Care Qual. PD OCT-DEC PY 2007 VL 22 IS 4 BP 322 EP 327 PG 6 WC Nursing SC Nursing GA 215TO UT WOS:000249832100006 PM 17873729 ER PT J AU Kaban, LB Troulis, MJ Wilkinson, MJ Ebb, D Dodson, TB AF Kaban, Leonard B. Troulis, Maria J. Wilkinson, Michael J. Ebb, David Dodson, Thomas B. TI Adjuvant antiangiogenic therapy for giant cell tumors of the jaws SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID RECOMBINANT INTERFERON ALFA-2A; ENDOTHELIAL GROWTH-FACTOR; CALCITONIN THERAPY; SPONTANEOUS REGENERATION; ALPHA-INTERFERON; GRANULOMA; LESIONS; BONE; HEMANGIOMAS; INFANCY AB Purpose: To further evaluate a novel treatment protocol for the management of aggressive giant cell lesions (GCLs) consisting of enucleation followed by adjuvant subcutaneous interferon alpha therapy. Patients and Methods: Using a retrospective case series study design, a sample of patients with aggressive GCLs was enrolled between April 1995 and June 2006. Lesions were enucleated with preservation of vital structures. Postoperatively, the patients received daily subcutaneous interferon alpha (3 million units/m(2) of body surface area). Interferon treatment continued with regular clinical and radiographic follow-up until the surgical defects filled in with bone, as demonstrated by panoramic radiographs and confirmed by computed tomography. Side effects, such as fever, fatigue, weight loss, decreased white blood cell count, decreased platelet count and elevated liver enzymes, were monitored. After completion of interferon therapy, patients followed for 2 years without evidence of recurrence were considered cured of disease. Results: The study sample was comprised of 26 subjects (65% female) with a mean age of 18.5 years. At the time of this writing, 16 of the subjects have completed the protocol and are cured of disease, 6 are in remission, and 4 are in active treatment. Four subjects experienced significant side effects from the interferon, requiring modification of treatment. Conclusions: Enucleation of aggressive GCLs with preservation of vital structures and adjuvant interferon is an excellent strategy for managing aggressive GCLs. Approximately 15% of subjects developed significant side effects limiting interferon administration and necessitating alternative therapies. (c) 2007 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, DMD Program, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Kaban, LB (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201, Boston, MA 02114 USA. EM LKaban@Partners.org NR 61 TC 34 Z9 34 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD OCT PY 2007 VL 65 IS 10 BP 2018 EP 2024 DI 10.1016/j.joms.2007.03.030 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 217HM UT WOS:000249939000018 PM 17884531 ER PT J AU Al-Mohaya, M Treister, N Al-Khadra, O Lehmann, L Padwa, B Woo, SB AF Al-Mohaya, Maha Treister, Nathaniel Al-Khadra, Ons Lehmann, Leslie Padwa, Bonnie Woo, Sook-Bin TI Calcineurin inhibitor-associated oral inflammatory polyps after transplantation SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE calcineurin inhibitor; immunosuppression; oral pathology; solid organ transplantation; stem cell transplantation ID CYCLOSPORINE-A; MARROW TRANSPLANTATION; GINGIVAL OVERGROWTH; PYOGENIC GRANULOMA; TACROLIMUS; HYPERPLASIA AB Calcineurin inhibitors (cyclosporine and tacrolimus) have been used as the mainstay immunosuppressive therapy for solid organ and hematopoietic cell transplantations (HCT) to prevent allograft rejection and for prophylaxis and treatment of the chronic graft-versus-host disease. Adverse effects of these drugs include nephrotoxicity, hepatotoxicity, neurotoxicity, hypertension and gingival hyperplasia. Association of oral non-gingival soft tissue hyperplasia with calcineurin inhibitor therapy has only recently been recognized and is thought to occur infrequently. We present four cases of oral non-gingival inflammatory fibro-vascular hyperplasias attributed to the use of calcineurin inhibitors following solid organ transplantation and HCT. These lesions interfere with function and must be differentiated from other oral lesions, and therefore should be surgically excised. C1 Brigham & Womens Hosp, Div Oral & Maxillofacial Surg, Boston, MA 02120 USA. Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Treister, N (reprint author), Brigham & Womens Hosp, Div Oral & Maxillofacial Surg, 1620 Tremont St,Suite BC 3-028, Boston, MA 02120 USA. EM ntreister@partners.org NR 20 TC 9 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0904-2512 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD OCT PY 2007 VL 36 IS 9 BP 570 EP 574 DI 10.1111/j.1600-0714.2007.00557.x PG 5 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA 210JI UT WOS:000249452100011 PM 17850443 ER PT J AU Qaseem, B Shea, J Connor, SR Casarett, D AF Qaseem, Brye Shea, Judy Connor, Stephen R. Casarett, David TI How well are we supporting hospice staff? Initial results of the survey of team attitudes and relationships (STAR) validation study SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE job satisfaction; hospice care; end-of-life care; work environment ID PHYSICIAN JOB-SATISFACTION; PRIMARY-CARE; PERFORMANCE; NURSES; ENVIRONMENT; PREDICTOR; OUTCOMES; SIZE AB Despite the emotional and interpersonal challenges that hospice staff face in providing care to patients near the end of life, no systematic effort has been made to evaluate the work environment that hospices provide to their staff. The aim of this project was to develop a job satisfaction survey that could be used to evaluate the hospice work environment and, ultimately, to guide interventions to improve the work experience for hospice staff. A first draft of the Survey of Team Attitudes and Relationships (STAR) was developed through semi-structured interviews with an interdisciplinary sample of staff from nine hospices, and then refined with input from additional interviews and from an expert panel. The draft was tested on larger samples of staff (n = 160)from six hospices and revised with input from, the expert panel. The final survey was tested with 599 staff from 10 hospices. The final survey contains 45 items in six domains: individual work rewards, teamwork, management support, organizational support, workload issues, and global assessment of job satisfaction. Items had excellent psychometric characteristics, with acceptable floor and ceiling effects. The overall STAR had a Cronbach's alpha of 0.93, indicating good homogeneity, and each domain had alpha values that are appropriate for between-group comparisons (range 0.74-0.84). These results suggest that the STAR offers a unique instrument to measure the work environment hospices provide to their staff. C1 Univ Penn, Ctr Hlth Equ Res & Promot, VAMC Res, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Natl Hosp & Palliat Care Org, Alexandria, VA USA. RP Casarett, D (reprint author), Univ Penn, Ctr Hlth Equ Res & Promot, VAMC Res, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu OI Connor, Stephen/0000-0003-0332-2067 NR 39 TC 5 Z9 5 U1 1 U2 3 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 2007 VL 34 IS 4 BP 350 EP 358 DI 10.1016/j.jpainsymman.2007.06.003 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 220MA UT WOS:000250159600005 PM 17716854 ER PT J AU Arnold, RM Back, A Billings, JA Block, S Meier, DE Morrison, RS AF Arnold, Robert M. Back, Anthony Billings, J. Andrew Block, Susan Meier, Diane E. Morrison, R. Sean TI Palliative medicine leadership forum 2006 SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Univ Pittsburgh, Sect Palliat Care & Ethics, Pittsburgh, PA 15260 USA. Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Mt Sinai Med Ctr, Ctr Adv Palliat Care, New York, NY 10029 USA. Mt Sinai Sch Med, Natl Palliat Care Res Ctr, Hertzberg Palliat Care Inst, Bronx, NY USA. RP Arnold, RM (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, 55 Fruit St, Boston, MA 02114 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 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD OCT PY 2007 VL 10 IS 5 BP 1029 EP 1030 DI 10.1089/jpm.2007.0067 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 233JB UT WOS:000251086100008 ER PT J AU Buss, MK Vanderwerker, LC Inouye, SK Zhang, B Block, SD Prigerson, HG AF Buss, Mary K. Vanderwerker, Lauren C. Inouye, Sharon K. Zhang, Baohui Block, Susan D. Prigerson, Holly G. TI Associations between Caregiver-Perceived delirium in patients with cancer and generalized anxiety in their caregivers SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID MENTAL STATUS QUESTIONNAIRE; STEM-CELL TRANSPLANTATION; FAMILY CAREGIVERS; TERMINAL CANCER; PSYCHIATRIC-DISORDERS; HOSPITALIZED-PATIENTS; COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; DEMENTIA; BURDEN AB Background: Delirium, a common complication of advanced cancer, may put caregivers at risk for poor mental health outcomes. We looked for a relationship between caregiver-perceived delirium in a patient with advanced cancer and rates of caregiver psychiatric disorders. Methods: Using cross-sectional data from 200 caregivers of patients with cancer with a life expectancy of less than 6 months, we determined the frequency of caregiver-perceived delirium, which was defined as caregivers who reported witnessing the patient "confused, delirious" on the Stressful Caregiving Response to Experiences of Dying (SCARED) weekly or more often. We tested for associations between caregiver-reported delirium and presence of caregiver mental disorders, using the Structured Clinical Interview for the DSM-IV to diagnose mental disorders and caregiver burden, as measured by the caregiver burden scale (CBS). Results: Of the 200 caregivers who completed the SCARED, 38 (19.0%) reported seeing the patient "confused, delirious" at least once per week in the month prior to study enrollment and 7 (3.5%) met criteria for generalized anxiety (GA). Caregivers of patients with caregiver-perceived delirium were 12 times more likely to have GA (odds ratio [OR] = 12.12; p<0.01). The relationship between caregiver-perceived delirium and caregiver GA persisted after adjusting for caregiver burden and exposure to other stressful patient experiences (OR = 9.99; p = 0.04). Conclusions: This is the first report of an association between caregiver-perceived delirium and a caregiver mental health outcome. Further studies, using improved measures of delirium, are needed. C1 Brigham & Womens Hosp, Harvard Med Sch, Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res,DPOPC, Boston, MA 02115 USA. Harvard Med Sch, Beth Israel Deaconess Med Ctr, Aging Brain Ctr, Dept Med,Hebrew Senior Life, Boston, MA USA. RP Buss, MK (reprint author), Dana Farber Canc Inst, Div Psychol Oncol & Palliat Care, Thorac Oncol Program, 44 Binney St,SW 411, Boston, MA 02115 USA. FU NCI NIH HHS [CA106370, R01 CA106370]; NIA NIH HHS [K24AG00949]; NIMH NIH HHS [MH56529, MH63892] NR 42 TC 32 Z9 33 U1 0 U2 4 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 2007 VL 10 IS 5 BP 1083 EP 1092 DI 10.1089/jpm.2006.0253 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 233JB UT WOS:000251086100018 PM 17985965 ER PT J AU Duffy, SA Copeland, LA Hopp, FP Zalenski, RJ AF Duffy, Sonia A. Copeland, Laurel A. Hopp, Faith P. Zalenski, Robert J. TI Diagnostic classifications and resource utilization of decedents served by the department of veterans affairs SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID DEPRESSIVE SYMPTOMS; ADVANCE DIRECTIVES; SOCIAL SUPPORT; LIFE; CARE; PREFERENCES; ETHNICITY; END; ATTITUDES; SMOKING AB Background: Given the volume and cost of inpatient care during the last year of life, there is a critical need to identify patterns of dying as a means of planning end-of-life care services, especially for the growing number of older persons who receive services from the Veterans Health Administration (VHA). Methods: A retrospective computerized record review was conducted of 20,933 VHA patients who died as inpatients between October 1, 2001 and September 30, 2002. Diagnoses were aggregated into one of five classification patterns of death and analyzed in terms of health care resource utilization ( mean number of inpatient days and cumulative outpatient visits in the year preceding the patient's death). Results: Cancer deaths were the most common (30.4%) followed by end-stage renal disease (ESRD) (23.2%), cardiopulmonary failure (21.4%), frailty (11.6%), "other" diagnoses (7.3%), and sudden deaths (6.1%). Those with ESRD were more likely to be male and nonwhite (p < 0.05) and those with frailty were more likely to be older and married (p < 0.05). Controlling for demographic variables, those with frailty had the highest number of inpatient days while those with ESRD had the highest number of outpatient visits. Nonmarried status was associated with more inpatient days, especially among younger decedents. Conclusion: As a recognized leader in end-of-life care, the VHA can play a unique role in the development of specific interventions that address the diverse needs of persons with different dying trajectories identified through this research. C1 VA Ctr Clin Management Res, Hlth Serv Res & Dev, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. S Texas Vet Hlth Care Syst VERDICT HSR, Dept Vet Affairs, San Antonio, TX USA. Wayne State Univ, Sch Social Work, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Ctr Adv Palliat Care Excellence, Dept Emergency Med, Detroit, MI 48202 USA. Wayne State Univ, Ctr Adv Palliat Care Excellence, Detroit, MI 48202 USA. RP Duffy, SA (reprint author), VA HSR&D Ctr Clin Management Res, VA Ann Arbor Heathcare Syst, Dept Vet Affairs, PO Box 130170, Ann Arbor, MI 48113 USA. OI Hopp, Faith/0000-0002-4536-3089; Copeland, Laurel/0000-0002-9478-0209 NR 39 TC 7 Z9 7 U1 4 U2 10 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 2007 VL 10 IS 5 BP 1137 EP 1145 DI 10.1089/jpm.2006.0256 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 233JB UT WOS:000251086100023 PM 17985970 ER PT J AU Knight, SJ Emanuel, L AF Knight, Sara J. Emanuel, Linda TI Processes of adjustment to end-of-life losses: A reintegration model SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID TERMINALLY-ILL PATIENTS; PSYCHOLOGICAL CONSIDERATIONS; SELF-TRANSCENDENCE; PALLIATIVE CARE; BAD-NEWS; DEATH; APPRAISAL; QUALITY; HEALTH; AGE AB The processes surrounding psychological adjustment to losses due to advancing and end-stage illness have not been well delineated. While adjustment to losses due to death are often thought of as the bereaved's lot, dying persons experience multiple, accumulating, and profound losses of functions, abilities, roles, and relationships and therefore have to adjust as well. Many people who are facing death in the near future negotiate these losses, still achieving quality of life in all dimensions. Others fare less well. It is hard to intervene helpfully without a clear understanding of how either trajectory occurs. Building from current literature on loss and adjustment, we describe a conceptual framework of key adjustment processes that allow for quality of life during terminal illness. We term this the reintegration model. It has comprehension, creative adaptation and reintegration components, each involving the physical, psychological, social, and existential domains in ways that are characteristic of the needs, tasks and options available to a seriously ill and dying person. In this paper, we discuss the model, focusing on normal adjustment processes, and describe the implications of the framework for the dying person, caregivers, and the palliative care team. C1 Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94143 USA. Northwestern Univ, Buehler Ctr Aging Hlth & Soc, Chicago, IL 60611 USA. RP Knight, SJ (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA 94143 USA. EM sara.knight@ucsf.edu NR 61 TC 25 Z9 25 U1 0 U2 2 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 2007 VL 10 IS 5 BP 1190 EP 1198 DI 10.1089/jpm.2006.0068 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 233JB UT WOS:000251086100028 PM 17985975 ER PT J AU Tkachenko, MA Zhannat, NZ Erman, LV Blashenkova, EL Isachenko, SV Isachenko, OB Graham, DY Malaty, HM AF Tkachenko, Mikhail A. Zhannat, Nurgalieva Z. Erman, Lev V. Blashenkova, Elena L. Isachenko, Sergey V. Isachenko, Olga B. Graham, David Y. Malaty, Hoda M. TI Dramatic changes in the prevalence of Helicobacter pylori infection during childhood: A 10-year follow-up study in Russia SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE Helicobacter pylori infection; epidemiology; Russia; transmission; childhood ID SOCIOECONOMIC-STATUS; GASTRIC-CANCER; PERUVIAN CHILDREN; BIRTH COHORT; AGE; RISK; EPIDEMIOLOGY; ACQUISITION; ASSOCIATION; ADULTS AB Background: The prevalence and rate of acquisition of Helicobacter pylori infection in children from developing countries is higher than in developed countries. This phenomenon has been related to differences in socioeconomic status, sanitation, and household hygiene. Russia is in the process of transforming from an underdeveloped to a developed country. Aim: To examine the effect of recent improvements in standards of living on the prevalence of H pylori in Russian children. Patients and Methods: We conducted 2 cross-sectional studies among children in St Petersburg, Russia. The first study was conducted in 1995 and the second was conducted a decade later. H pylori status was evaluated by the same enzyme-linked immunoassay method for anti-H pylori immunoglobulin G. Demographic data were obtained from each individual, and socioeconomic class was assessed by the education level of the mother and family income. Results: In 1995 the overall prevalence of H pylori infection was 44%; 10 years later it had decreased to 13%. In both studies, the prevalence increased with age. In 1995 the prevalence was 30% among children younger than 5 years. A decade later the prevalence in the same age group was 2% (P=0.001). The age-specific prevalence of H pylori infection increased significantly with age in both study periods. During 1995 the prevalence of the infection increased from 30% at age < 5 years to 48% in the age group 15 to 19 years (P = 0.001). In the 2005 study the prevalence of the infection increased from 2% at age < 5 years to 25% in the age group 15 to 19 years (P = 0.00 1). The crude and the age-adjusted odds ratio risk of infection in children showed an inverse correlation between the mothers' and fathers' educational levels and H pylori seropositivity (OR 1.8, 95% Cl 1-3.2; P = 0.06). No associations were found between the prevalence of H pylori and any factor tested, including sex, type of dwelling, income, or the number of people living in the home. Conclusions: Improvements in standards of living in Russia have resulted in a marked reduction in H pylori transmission. Different rates of acquisition of Hpylori form the basis for the differences in prevalence of infection between and among populations. The change in the prevalence of H pylori within 10 years among the Russian population is an example of how sensitive Hpylori acquisition is to improvement in standards of living. Increased use of anti-H pylori eradication therapy played an important role in the reduction of the prevalence of Hpylori infection. JPGN 45:428-432, 2007. C1 Vet Affairs Med Ctr 111D, Dept Med, Houston, TX 77030 USA. St Petersburg State Pediat Med Acad, Dept Pediat 1, St Petersburg, Russia. St Petersburg State Pediat Med Acad, Div Otorhinolaryngol, Med Ctr Children 2, St Petersburg, Russia. Baylor Coll Med, Houston, TX 77030 USA. RP Malaty, HM (reprint author), Vet Affairs Med Ctr 111D, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM Hmalaty@bcm.tmc.edu NR 30 TC 55 Z9 59 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD OCT PY 2007 VL 45 IS 4 BP 428 EP 432 PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 212OQ UT WOS:000249607100007 PM 18030208 ER PT J AU Liu, RW Mehta, P Fortuna, S Armstrong, DG Cooperman, DR Thompson, GH Gilmore, A AF Liu, Raymond W. Mehta, Priyesh Fortuna, Suzanne Armstrong, Douglas G. Cooperman, Daniel R. Thompson, George H. Gilmore, Allison TI A Randomized Prospective Study of Music Therapy for Reducing Anxiety During Cast Room Procedures SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE anxiety; music therapy; cast room procedures AB Background: Cast room procedures, such as cast application and removal, pin removal, and suture removal can cause significant anxiety in young children. The use of music therapy in the cast room to decrease anxiety has not been previously reported. Methods: We performed a randomized, prospective study of soft lullaby music compared with no music in 69 children 10 years or younger undergoing cast room procedures. Heart rates (beats per minute) were recorded in the waiting room and cast room using a pulse oximeter. Results: A total of 28 children were randomized to music and 41 children to no music. The mean rise in heart rate between the waiting room and entering the cast room was -2.7 beats/min in the music group and 4.7 beats/min in the no music group (P = 0.001). The mean difference in heart rate between the waiting room and during the procedure was 15.3 beats/min in the music group and 22.5 beats/min in the no music group (P = 0.05). There were 7 patients in the no music group with heart rate increases of greater than 40 beats/min. No patient in the music group had an increase of this magnitude. Conclusions: Playing soft music in the cast room is a simple and inexpensive option for decreasing anxiety in young children during cast room procedures. C1 [Fortuna, Suzanne; Armstrong, Douglas G.; Cooperman, Daniel R.; Thompson, George H.; Gilmore, Allison] Rainbow Babies & Childrens Hosp, Div Pediat Orthopaed Surg, Cleveland, OH 44106 USA. [Liu, Raymond W.] Case Western Reserve Univ, Dept Orthopaed, Cleveland, OH 44106 USA. [Mehta, Priyesh] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Gilmore, A (reprint author), Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Div Pediat Orthopaed, Case Med Ctr, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM Allison.Gilmore@uhhs.com NR 6 TC 16 Z9 16 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD OCT-NOV PY 2007 VL 27 IS 7 BP 831 EP 833 DI 10.1097/BPO.0b013e3181558a4e PG 3 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA V01RN UT WOS:000206872800022 PM 17878794 ER PT J AU Putterman, DB Munhall, AC Kozell, LB Belknap, JK Johnson, SW AF Putterman, Daniel B. Munhall, Adam C. Kozell, Laura B. Belknap, John K. Johnson, Steven W. TI Evaluation of levodopa dose and magnitude of dopamine depletion as risk factors for levodopa-induced dyskinesia in a rat model of Parkinson's disease SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ABNORMAL INVOLUNTARY MOVEMENTS; NMDA RECEPTOR SUBUNITS; MOTOR FLUCTUATIONS; STRIATAL LESIONS; MESSENGER-RNA; 6-OHDA LESION; EXPRESSION; INCREASE; PRODYNORPHIN; STIMULATION AB Levodopa dose and severity of Parkinson's disease (PD) are recognized risk factors for levodopa-induced dyskinesia ( LID) in humans. The purpose of the present study was to evaluate the ability of these variables to predict severity of LID in a rat model of PD. Varied concentrations of 6-hydroxy-dopamine were injected into the midbrain to produce wide ranges of dopamine depletion in striatum. Three weeks later, rats were given daily injections of levodopa (2-10 mg/kg i.p.) plus benserazide (12.5 mg/kg i.p.) for 15 days. Abnormal involuntary movements (AIMs) were measured for limb, axial, orolingual, and rotatory movements. Dose-response analysis for total AIM scores yielded a levodopa ED50 value of 3.2 mg/kg on treatment day 15. There were strong interrelated correlations between individual AIM categories (rho > 0.7) and for each AIM category in regard to total AIM score (rho > 0.7). In rats that received levodopa doses that were greater than the ED50, rates of amphetamine-induced rotation were significantly correlated with total AIM scores (rho=0.413). However, of those rotating > 5 times/min, 34% had relatively low AIM scores (< 8). Likewise, there was a significant correlation between percentages of tyrosine hydroxylase (TH) loss and total AIM scores (rho=0.388). However, in those rats that had > 85% TH loss, 30% had AIM scores < 8. Our results show that given an adequate dose and magnitude of striatal dopamine depletion, levodopa produces dyskinesia with a continuous spectrum of severity. Although levodopa dose and level of dopamine depletion are significant risk factors for LID, we conclude that other factors must contribute to LID susceptibility. C1 Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, Res Serv, RD-61,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM johnsost@ohsu.edu OI Kozell, Laura/0000-0003-3059-2046 FU NINDS NIH HHS [R01 NS038715, NS38715] NR 41 TC 39 Z9 40 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 2007 VL 323 IS 1 BP 277 EP 284 DI 10.1124/jpet.107.126219 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 212IF UT WOS:000249588900032 PM 17660384 ER PT J AU Bouali, H Nietert, P Nowling, TM Pandey, J Dooley, MA Cooper, G Harley, J Kamen, DL Oates, J Gilkeson, G AF Bouali, Henda Nietert, Paul Nowling, Tamara M. Pandey, Janardan Dooley, Mary Anne Cooper, Glinda Harley, John Kamen, Diane L. Oates, Jim Gilkeson, Gary TI Association of the G-463A myeloperoxidase gene polymorphism with renal disease in African Americans with systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; myeloperoxidase; polymorphism; African American; lupus nephritis ID NITRIC-OXIDE SYNTHASE; PROMOTER POLYMORPHISMS; RISK; MICE; DNA; ATHEROSCLEROSIS; PEROXIDASES; EXPRESSION; KIDNEY; MPO AB Objective. Myeloperoxidase (MPO) is an enzyme expressed in neutrophils that is involved in tissue damage in inflammatory renal diseases. A functional G to A single-nucleotide polymorphism (SNP) is present at position -463 of the MPO promoter region and is associated with altered MPO expression. We hypothesized that the G-463A MPO SNP is a risk factor for developing lupus nephritis (LN) due to its potential influence on the inflammatory response. Methods. DNA from 229 patients with SLE and 277 controls from the Carolina Lupus cohort, 58 African American patients from the Sea Island Lupus Cohort, and 51 African American patients from the Lupus Multiplex Registry and Repository were genotyped by PCR. A linear regression model was used to examine relationships between the MPO genotype, case/control status, demographic characteristics, and LN. Results. There was no association of MPO genotype with systemic lupus erythematosus (SLE). However, the odds of developing LN were significantly higher among those with an A allele, compared to those without, in African American cases of all 3 cohorts. When the likelihood of developing LN was compared across MPO genotypes, the risk of developing LN was significantly higher among cases with a GA genotype versus GG (OR 2.11, 95% CI 1.12 to 3.97) and even higher with AA versus GG (OR 3.52, 95% CI 1.41 to 8.77). Conclusion. While the G-463A MPO SNP is not a risk factor for developing SLE, the low expressing A allele is a significant risk factor for developing LN that is gene dosage-dependent in African Americans. C1 Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. Univ N Carolina, Affiliated Hosp, Dept Med, Chapel Hill, NC 27515 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Gilkeson, G (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, 96 Jonathan Lucas St,Suite 912,POB 250623, Charleston, SC 29425 USA. EM gilkeson@musc.edu OI Nietert, Paul/0000-0002-3933-4986 FU NCRR NIH HHS [M01 RR001070-280263, M01 RR001070-220263, M01 RR001070-25A10263, M01 RR001070-240263, M01 RR001070, M01 RR001070-24S50263, M01 RR001070-25A1S20263, M01 RR001070-230263, M01 RR001070-260263, M01 RR001070-270263, M01 RR001070-25A1S10263]; NIAMS NIH HHS [P60 AR049459, AR47469, P30 AR053483] NR 49 TC 15 Z9 18 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2007 VL 34 IS 10 BP 2028 EP 2034 PG 7 WC Rheumatology SC Rheumatology GA 217OB UT WOS:000249956100015 PM 17896805 ER PT J AU Wiedemann-Bidlack, FB Beniash, E Yamakoshi, Y Simmer, JP Margolis, HC AF Wiedemann-Bidlack, Felicitas B. Beniash, Elia Yamakoshi, Yasuo Simmer, James P. Margolis, Henry C. TI pH triggered self-assembly of native and recombinant amelogenins under physiological pH and temperature in vitro SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE enamel; biomineralization; amelogenin; self-assembly; dynamic light scattering; turbidity ID DYNAMIC LIGHT-SCATTERING; EMBRYONIC BOVINE ENAMEL; DENTAL ENAMEL; HYDROXYAPATITE CRYSTALS; MECHANICAL-PROPERTIES; PORCINE-AMELOGENINS; SECRETORY-STAGE; DNA-SEQUENCE; PROTEIN; MATRIX AB Self-assembly of the extracellular matrix protein amelogenin is believed to play an essential role in regulating the growth and organization of enamel crystals during enamel formation. This study examines the effect of temperature and pH on amelogenin self-assembly under physiological pH conditions in vitro, using dynamic light scattering, turbidity measurements, and transmission electron microscopy. Full-length recombinant amelogenins from mouse (rM179) and pig (rP172) were investigated, along with proteolytic cleavage products (rM166 and native P148) lacking the hydrophilic C-terminus of parent molecules. Results indicated that the self-assembly of full-length amelogenin is primarily triggered by pH in the temperature range from 13 to 37 degrees C and not by temperature. Furthermore, very large assemblies of all proteins studied formed through the rearrangement of similarly sized nanospherical particles, although at different pH values: pH 7.7 (P148), pH 7.5 (rM166), pH 7.2 (rP172), and pH 7.2 (rM179). Structural differences were also observed. The full-length molecules formed apparently tightly connected elongated, high-aspect ratio assemblies comprised of small spheres, while the amelogenin cleavage products appeared as loosely associated spherical particles, suggesting that the hydrophilic C-terminus plays an essential role in higher-order amelogenin assembly. Hence, tightly controlled pH values during secretory amelogenesis may serve to regulate the functions of both full-length and cleaved amelogenins. (c) 2007 Elsevier Inc. All rights reserved. C1 Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Harvard Univ, Dept Anthropol, Cambridge, MA 02138 USA. Univ Michigan, Dent Res Lab, Ann Arbor, MI 48109 USA. RP Margolis, HC (reprint author), Forsyth Inst, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. EM hmargolis@forsyth.org FU NIDCR NIH HHS [DE-016376, R56 DE016376, T32 DE007327, R01 DE016376, T32 DE007327-02, T32 DE-007327, R01 DE016376-02] NR 66 TC 48 Z9 48 U1 0 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD OCT PY 2007 VL 160 IS 1 BP 57 EP 69 DI 10.1016/j.jsb.2007.06.007 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 215UN UT WOS:000249834600006 PM 17719243 ER PT J AU Voss, SE Rosowski, JJ Merchant, SN AF Voss, Susan E. Rosowski, John J. Merchant, Saumil N. TI Non-ossicular signal transmission in human middle ears: Experimental assessment of the "acoustic route" with perforated tympanic membranes SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID SOUND-TRANSMISSION; MECHANICS; COCHLEA AB Direct acoustic stimulation of the cochlea by the sound-pressure difference between the oval and round windows (called the "acoustic route") has been thought to contribute to hearing in some pathological conditions, along with the normally dominant "ossicular route." To determine the efficacy of this acoustic route and its constituent mechanisms in human ears, sound pressures were measured at three locations in cadaveric temporal bones [with intact and perforated tympanic membranes (TMs)]: (1) in the external ear canal lateral to the TM, P-TM; (2) in the tympanic cavity lateral to the oval window, P-OW; and (3) near the round window, P-RW. Sound transmission via the acoustic route is described by two concatenated processes: (1) coupling of sound pressure from ear canal to middle-ear cavity, H-P CAV P-CAV/P-TM, where P-CAV represents the middle-ear cavity pressure, and (2) sound-pressure difference between the windows, H-WPD (P-OW-P-RW)/P-CAV. Results show that: H-PCAV depends on perforation size but not perforation location; H-WPD depends on neither perforation size nor location. The results (1) provide a description of the window pressures c based on measurements, (2) refute the common otological view that TM perforation location affects the "relative phase of the pressures at the oval and round windows," and (3) show with an intact ossicular chain that acoustic-route transmission is substantially below ossicular-route transmission except for low frequencies with large perforations. Thus, hearing loss from TM perforations results primarily from reduction in sound coupling via the ossicular route. Some features of the frequency dependence of H-PCAV and H-WPD can be interpreted in terms of a structure-based lumped-element acoustic model of the perforation and middle-ear cavities. (c) 2007 Acoustical Society of America. C1 Smith Coll, Picker Engn Program, Northampton, MA 01063 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Voss, SE (reprint author), Smith Coll, Picker Engn Program, 51 Coll Lane, Northampton, MA 01063 USA. EM svoss@email.smith.edu FU NIDCD NIH HHS [R01 DC004798, R01 DC004798-07] NR 25 TC 15 Z9 17 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 2007 VL 122 IS 4 BP 2135 EP 2153 DI 10.1121/1.2769617 PG 19 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 218PI UT WOS:000250027000030 PM 17902851 ER PT J AU Ravicz, ME Olson, ES Rosowski, JJ AF Ravicz, Michael E. Olson, Elizabeth S. Rosowski, John J. TI Sound pressure distribution and power flow within the gerbil ear canal from 100 Hz to 80 kHz SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BAND REFLECTANCE TYMPANOMETRY; ACOUSTIC ENERGY REFLECTANCE; MIDDLE-EAR; MONGOLIAN GERBIL; TYMPANIC MEMBRANE; MERIONES-UNGUICULATUS; SPATIAL-DISTRIBUTION; RADIATION IMPEDANCE; AUDITORY PERIPHERY; HIGH-FREQUENCIES AB Sound pressure was mapped in the bony ear canal of gerbils during closed-field sound stimulation at frequencies from 0.1 to 80 kHz. A 1.27-mm-diam probe-tube microphone or a 0.17-mm-diam fiber-optic miniature microphone was positioned along approximately longitudinal trajectories within the 2.3-mm-diam ear canal. Substantial spatial variations in sound pressure, sharp minima in magnitude, and half-cycle phase changes occurred at frequencies >30 kHz. The sound frequencies of these transitions increased with decreasing distance from the tympanic membrane (TM). Sound pressure measured orthogonally across the surface of the TM showed only small variations at frequencies below 60 kHz. Hence, the ear canal sound field can be described fairly well as a one-dimensional standing wave pattern. Ear-canal power reflectance estimated from longitudinal spatial variations was roughly constant at 0.2-0.5 at frequencies between 30 and 45 kHz. In contrast, reflectance increased at higher frequencies to at least 0.8 above 60 kHz. Sound pressure was also mapped in a microphone-terminated uniform tube-an "artificial ear." Comparison with ear canal sound fields suggests that an artificial ear or "artificial cavity calibration" technique may underestimate the in situ sound pressure by 5-15 dB between 40 and 60 kHz. (c) 2007 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Columbia Univ, Dept Otolaryngol Head & Neck Surg, New York, NY 10032 USA. Biomed Engn Dept, New York, NY 10027 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM mike_ravicz@meei.harvard.edu FU NIDCD NIH HHS [R01 DC000194, R01 DC000194-24, R01 DC004798, R01 DC004798-07] NR 62 TC 26 Z9 26 U1 0 U2 1 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 2007 VL 122 IS 4 BP 2154 EP 2173 DI 10.1121/1.2769625 PG 20 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 218PI UT WOS:000250027000031 PM 17902852 ER PT J AU Fitzgerald, BT Setty, A Mudgal, CS AF Fitzgerald, Brian T. Setty, Arathi Mudgal, Chaitanya S. TI Gout affecting the hand and wrist SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID CARPAL-TUNNEL-SYNDROME; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NUTRITION EXAMINATION SURVEY; PURINE SELECTIVE INHIBITOR; TOPHACEOUS GOUT; MEDIAN NERVE; SURGICAL MANAGEMENT; SYNDROME SECONDARY; XANTHINE-OXIDASE; NATIONAL-HEALTH AB Tophaceous gout in the hand and wrist often presents de novo as the first sign of the disease process in the elderly. Tophaceous material may present in a liquid, pasty, or chalky/granular state. Treatment may be as simple as aspirating the liquid or squeezing out pasty tophaceous material. Other nonsurgical treatment options include lifestyle and dietary modifications and drug therapy. Surgery is often indicated for the patient with significant tendon and joint compromise as well as skin breakdown and for decompression of compressive peripheral neuropathy. C1 Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. Naval Med Ctr, San Diego, CA USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Cambridge, MA 02138 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Suite 2100,Yawkey Ctr,55 Fruit St, Boston, MA 02114 USA. NR 49 TC 10 Z9 12 U1 0 U2 0 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD OCT PY 2007 VL 15 IS 10 BP 625 EP 635 PG 11 WC Orthopedics SC Orthopedics GA 238BP UT WOS:000251422600007 PM 17916786 ER PT J AU McGory, ML Zingmond, DS Tillou, A Hiatt, JR Ko, CY Cryer, HM AF McGory, Marcia L. Zingmond, David S. Tillou, Areti Hiatt, Jonathan R. Ko, Clifford Y. Cryer, Henry M. TI Negative appendectomy in pregnant women is associated with a substantial risk of fetal loss SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SUSPECTED ACUTE APPENDICITIS; LAPAROSCOPIC APPENDECTOMY; DIAGNOSTIC-ACCURACY; MANAGEMENT; OUTCOMES; SURGERY AB Background: The preoperative diagnosis of acute appendicitis is often inaccurate in pregnant women, and complicated appendicitis is associated with a high rate of fetal loss. The study objective was to evaluate rates of fetal loss and early delivery in pregnant patients undergoing appendectomy, using a large population-based database. Study Design: Using the California Inpatient File, we retrospectively analyzed all women undergoing appendectomy between 1995 and 2002 for pregnancy, diagnosis, operative technique, fetal loss, and early delivery during the same hospitalization as appendectomy. Results: Of 94,789 women who underwent appendectomy, 3,133 were pregnant. Complicated appendicitis was found in 30% of pregnant women and 29% of nonpregnant women (p = NS). The rate of negative appendectomy was considerably higher in pregnant compared with nonpregnant women (23% versus 18%, p < 0.05). Rates of fetal loss and early delivery were considerably higher in women with complex appendicitis (6% and 11% respectively; p < 0.05) in comparison with negative (4% and 10%) and simple (2% and 4%) appendicitis. Using multivariate logistic regression, complicated and negative appendicitis (odds ratio [OR] 2.69 and 1.88 respectively, compared with simple) remained major positive predictors of fetal loss. Also, laparoscopy was associated with a higher rate of fetal loss compared with open appendectomy (odds ratio = 2.31). Conclusions: The current approach to possible acute appendicitis in pregnant women puts 23% at risk for fetal loss, even though they have a normal appendix. These data indicate that reducing fetal loss in pregnant women suspected of having acute appendicitis will require more accurate diagnosis to avoid unnecessary operation. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Ctr Surg Outcomes & Qual, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP McGory, ML (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Ctr Hlth Sci 72 215, 10833 Le Conte Ave,Box 956904, Los Angeles, CA 90095 USA. NR 30 TC 76 Z9 85 U1 0 U2 2 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 2007 VL 205 IS 4 BP 534 EP 540 DI 10.1016/j.jamcollsurg.2007.05.025 PG 7 WC Surgery SC Surgery GA 222QP UT WOS:000250312300002 PM 17903726 ER PT J AU Bilimoria, KY Bentrem, DJ Merkow, RP Tomlinson, JS Stewart, AK Ko, CY Talamonti, MS AF Bilimoria, Karl Y. Bentrem, David J. Merkow, Ryan P. Tomlinson, James S. Stewart, Andrew K. Ko, Clifford Y. Talamonti, Mark S. TI Application of the pancreatic adenocarcinoma staging system to pancreatic neuroendocrine tumors SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID LONG-TERM SURVIVAL; ENDOCRINE TUMORS; CLASSIFICATION; SURGERY AB Background: The American Joint Committee on Cancer (AJCC) 6(th) edition staging system for pancreatic adenocarcinoma specifically excludes pancreatic neuroendocrine tumors (PNETs), and a widely accepted staging classification does not exist. Our objective was to evaluate the feasibility of applying the AJCC pancreatic adenocarcinoma staging system to PNETs. Study Design: Patients with PNETs were identified from the National Cancer Data Base (1985 to 2004). Overall survival was estimated using the Kaplan-Meier method and compared using the logrank test. Cox proportional hazards modeling was used to evaluate the effect of tumor size, nodal status, and distant metastases on survival. Results: Of 4,793 patients with PNETs, 93.6% were of islet cell origin, and 6.4% were carcinoid tumors; 1,815 (37.9%) underwent resection. Overall 5-year survival rates were 29.2% for all patients, 55.4% for resected patients, and 15.6% for unresected patients. The AJCC staging system provided good prognostic survival discrimination between stage groups for resected patients (p < 0.0001). When comparing outcomes to those of patients with pancreatic adenocarcinoma, the estimated median survival was significantly better for resected patients with PNETs (60 versus 13 months, p < 0.0001). Distant metastasis was the only independent predictor of survival (p < 0.0001). Conclusions: When applied to PNETs, the AJCC staging system for pancreatic adenocarcinoma provides survival discrimination by stage for surgical and nonsurgical patients. Survival rates are better for PNETs than for pancreatic adenocarcinoma, but the staging system can effectively stratify patients with PNETs. C1 Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. Amer Coll Surg, Canc Programs, Chicago, IL USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Talamonti, MS (reprint author), NW Mem Hosp, Dept Surg, Div Surg Oncol, 675 N St Clair St,Galter 10-105, Chicago, IL 60611 USA. NR 21 TC 54 Z9 55 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 2007 VL 205 IS 4 BP 558 EP 563 DI 10.1016/j.jamcollsurg.2007.05.009 PG 6 WC Surgery SC Surgery GA 222QP UT WOS:000250312300005 PM 17903729 ER PT J AU Fried, LF Boudreau, R Lee, JS Chertow, G Kurella-Tamura, M Shlipak, MG Ding, J Sellmeyer, D Tylavsky, FA Simsonick, E Kritchevsky, SB Harris, TB Newman, AB AF Fried, Linda F. Boudreau, Robert Lee, Jung Sun Chertow, Glenn Kurella-Tamura, Manjula Shlipak, Michael G. Ding, Jingzhong Sellmeyer, Deborah Tylavsky, Frances A. Simsonick, Eleanor Kritchevsky, Stephen B. Harris, Tamara B. Newman, Anne B. CA Hlth, Aging Body Composition Study TI Kidney function as a predictor of loss of lean mass in older adults: Health, aging and body composition study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE kidney function; elderly; weight loss; body composition; sarcopenia ID MUSCLE PROTEIN BREAKDOWN; CHRONIC-RENAL-FAILURE; SKELETAL-MUSCLE; WEIGHT-LOSS; HEMODIALYSIS-PATIENTS; NUTRITIONAL-STATUS; DISEASE; INFLAMMATION; MORTALITY; MEN AB OBJECTIVES: To assess the association between kidney function and change in body composition in older individuals. DESIGN: Prospective cohort study. SETTING: Two sites, Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Three thousand twenty-six well-functioning, participants aged 70 to 79 in the Health, Aging and Body Composition Study. MEASUREMENTS: Body composition (bone-free lean mass and fat mass) was measured using dual x-ray absorptiometry annually for 4 years. Kidney function was measured at baseline according to serum creatinine (SCr). Comorbidity and inflammatory markers were evaluated as covariates in mixed-model, repeated-measures analysis. RESULTS: High SCr was associated with loss of lean mass in men but not women, with a stronger relationship in black men (P=.02 for difference between slopes for white and black men). In white men, after adjustment for age and comorbidity, higher SCr remained associated with loss of lean mass (-0.07 +/- 0.03 kg/y greater loss per 0.4 mg/dL (1 standard deviation (SD)), P=.009) but was attenuated after adjustment for inflammatory factors (-0.05 +/- 0.03 kg/y greater loss per SD, P=.10). In black men, the relationship between SCr and loss of lean mass (-0.19 +/- 0.04 kg/y per SD, P <.001) persisted after adjustment for inflammation and overall weight change. CONCLUSION: Impaired kidney function may contribute to loss of lean mass in older men. Inflammation appeared to mediate the relationship in white but not black men. Future studies should strive to elucidate mechanisms linking kidney disease and muscle loss and identify treatments to minimize loss of lean mass and its functional consequences. C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Renal Electrolyte Div, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. Univ Calif San Francisco, Div Endocrinol & Metab, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Nephrol, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Tennessee, Dept Biostat & Epidemiol, Memphis, TN USA. NIA, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. RP Fried, LF (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Univ Dr,Mailstop 111F-U, Pittsburgh, PA 15240 USA. EM Linda.Fried@va.gov RI Newman, Anne/C-6408-2013; Kurella Tamura, Manjula/C-8284-2014; OI Newman, Anne/0000-0002-0106-1150; Kurella Tamura, Manjula/0000-0001-5227-2479; Boudreau, Robert/0000-0003-0162-5187; Kritchevsky, Stephen/0000-0003-3336-6781 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 31 TC 13 Z9 13 U1 0 U2 3 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 2007 VL 55 IS 10 BP 1578 EP 1584 DI 10.1111/j.1532-5415.2007.01398.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 215RA UT WOS:000249825500011 PM 17908060 ER PT J AU Sayers, SL Hanrahan, N Kutney, A Clarke, SP Reis, BF Riegel, B AF Sayers, Steven L. Hanrahan, Nancy Kutney, Ann Clarke, Sean P. Reis, Brendali F. Riegel, Barbara TI Psychiatric comorbidity and greater hospitalization risk, longer length of stay, and higher hospitalization costs in older adults with heart failure SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE heart failure; psychiatric comorbidity; depression; hospitalization costs; economic analysis; Medicare; sex; socioeconomic status; race/ethnicity ID PRIMARY-CARE; LATE-LIFE; DEPRESSION; PREVALENCE; DISORDERS; DIAGNOSIS; MORTALITY; BIAS AB OBJECTIVES: To explore associations between psychiatric comorbidity and rehospitalization risk, length of hospitalization, and costs. DESIGN: Cross-sectional study of 1-year hospital administrative data. SETTING: Claims-based study of older adults hospitalized in the United States. PARTICIPANTS: Twenty-one thousand four hundred twenty-nine patients from a 5% national random sample of U.S. Medicare beneficiaries aged 65 and older, with at least one acute care hospitalization in 1999 with a Diagnostic-Related Group of congestive heart failure. MEASUREMENTS: The number of hospitalizations, mean length of hospital stay, and total hospitalization costs in calendar year 1999. RESULTS: Overall, 15.8% of patients hospitalized for heart failure (HF) had a coded psychiatric comorbidity; the most commonly coded comorbid psychiatric disorder was depression (8.5% of the sample). Most forms of psychiatric comorbidity were associated with greater inpatient utilization, including risk of additional hospitalizations, days of stay, and hospitalization charges. Additional hospitalization costs associated with psychiatric comorbidity ranged up to $7,763, and additional days length of stay ranged up to 1.4 days. CONCLUSIONS: Psychiatric comorbidity appears in a significant minority of patients hospitalized for HF and may affect their clinical and economic outcomes. The associations between psychiatric comorbidity and use of inpatient care are likely to be an underestimate, because psychiatric illness is known to be underdetected in older adults and in hospitalized medical patients. C1 Vet Affairs Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Hlth Outcomes & Policy Res, Philadelphia, PA 19104 USA. Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Widener Univ, Inst Grad Clin Psychol, Philadelphia, PA USA. RP Sayers, SL (reprint author), Vet Affairs Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, MIRECC 116,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM steven.sayers@va.gov FU NINR NIH HHS [P30-NR-005043, T32-NR-007104] NR 30 TC 35 Z9 36 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2007 VL 55 IS 10 BP 1585 EP 1591 DI 10.1111/j.1532-5415.2007.01368.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 215RA UT WOS:000249825500012 PM 17714458 ER PT J AU Arora, VM McGory, ML Fung, CH AF Arora, Vineet M. McGory, Marcia L. Fung, Constance H. TI Quality indicators for hospitalization and surgery in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Review DE quality indicators; hospitalization; surgery; vulnerable elders ID COMMUNITY-ACQUIRED PNEUMONIA; CONFUSION ASSESSMENT METHOD; INTENSIVE-CARE-UNIT; MAJOR NONCARDIAC SURGERY; MECHANICALLY VENTILATED PATIENTS; INDWELLING URINARY CATHETERS; PROSPECTIVE PAYMENT SYSTEM; SURGICAL SITE INFECTIONS; FATAL PULMONARY-EMBOLISM; CORONARY-ARTERY DISEASE C1 Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Ctr Surg Outcomes & Qual, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Arora, VM (reprint author), Univ Chicago, Dept Med, 5841 S Maryland Ave,MC 2007 W216, Chicago, IL 60637 USA. EM varora@medicine.bsd.uchicago.edu OI Arora, Vineet/0000-0002-4745-7599 NR 125 TC 26 Z9 26 U1 6 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2007 VL 55 SU 2 BP S347 EP S358 DI 10.1111/j.1532-5415.2007.01342.x PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400014 PM 17910557 ER PT J AU Bates-Jensen, BM MacLean, CH AF Bates-Jensen, Barbara M. MacLean, Catherine H. TI Quality indicators for the care of pressure ulcers in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Review DE pressure ulcer prevention; pressure ulcer treatment; quality indicators ID NURSING-HOME RESIDENTS; RISK-ASSESSMENT SCALES; RANDOMIZED TRIAL; CHRONIC WOUNDS; HYDROCOLLOID DRESSINGS; COST-EFFECTIVENESS; INTENSIVE-CARE; HEALTH-CARE; SORES; DEBRIDEMENT C1 VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. RAND Hlth, Santa Monica, CA USA. RP Bates-Jensen, BM (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, 16111 Plummer St 11E, Sepulveda, CA 91343 USA. EM bbatesjensen@sonnet.ucla.edu NR 126 TC 9 Z9 9 U1 3 U2 5 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 2007 VL 55 SU 2 BP S409 EP S416 DI 10.1111/j.1532-5415.2007.01349.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400021 PM 17910564 ER PT J AU Chang, JT Ganz, DA AF Chang, John T. Ganz, David A. TI Quality indicators for falls and mobility problems in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Review DE quality indicators; quality of care; falls; mobility problems; gait; instability; balance; exercise; elderly; vulnerable elders ID RANDOMIZED CONTROLLED-TRIAL; LOWER-EXTREMITY STRENGTH; HOME-BASED EXERCISE; TAI-CHI EXERCISE; OLDER-ADULTS; RISK-FACTORS; PREVENT FALLS; VITAMIN-D; INJURIOUS FALLS; MULTIFACTORIAL INTERVENTION C1 Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Specialty Training & Adv Res Program, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Chang, JT (reprint author), Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Ave,3rd Floor, Los Angeles, CA 90095 USA. EM jtchang@ucla.edu NR 108 TC 37 Z9 39 U1 6 U2 10 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 2007 VL 55 SU 2 BP S327 EP S334 DI 10.1111/j.1532-5415.2007.01339.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400011 PM 17910554 ER PT J AU Cheng, EM Fung, CH AF Cheng, Eric M. Fung, Constance H. TI Quality indicators for the care of stroke and atrial fibrillation in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE stroke; atrial fibrillation; quality indicators ID ACUTE ISCHEMIC-STROKE; AMERICAN-HEART-ASSOCIATION; PLACEBO-CONTROLLED TRIAL; ACADEMY-OF-NEUROLOGY; HIGH-RISK PATIENTS; TISSUE-PLASMINOGEN ACTIVATOR; RANDOMIZED CONTROLLED-TRIALS; THROMBOLYTIC THERAPY; ANTITHROMBOTIC THERAPY; OCCUPATIONAL-THERAPY C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Cheng, EM (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Neurol, 11301 Wilshire Blvd,ML 127,B500, Los Angeles, CA 90073 USA. EM Eric.Cheng@va.gov NR 72 TC 5 Z9 5 U1 0 U2 1 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 2007 VL 55 SU 2 BP S431 EP S437 DI 10.1111/j.1532-5415.2007.01352.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400024 PM 17910567 ER PT J AU Etzioni, S Chodosh, J Ferrell, BA MacLean, CH AF Etzioni, Shiri Chodosh, Joshua Ferrell, Bruce A. MacLean, Catherine H. TI Quality indicators for pain management in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pain management; quality of care; process measures ID CANCER PAIN; NURSING-HOME; GENERAL-POPULATION; OLDER PERSONS; PREVALENCE; HEALTH; GUIDELINES; COMPLAINTS; RESIDENTS; EDUCATION C1 RAND Hlth Corp, Santa Monica, CA 90407 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Wellpoint Inc, Programs Clin Excellence, Thousand Oaks, CA USA. RP MacLean, CH (reprint author), RAND Hlth Corp, 1776 Main St,M4337, Santa Monica, CA 90407 USA. EM maclean@rand.org OI Chodosh, Joshua/0000-0001-7784-4306 NR 52 TC 10 Z9 10 U1 0 U2 1 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 2007 VL 55 SU 2 BP S403 EP S408 DI 10.1111/j.1532-5415.2007.01348.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400020 PM 17910563 ER PT J AU Feil, DG MacLean, C Sultzer, D AF Feil, Denise G. MacLean, Catherine Sultzer, David TI Quality indicators for the care of dementia in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Review DE dementia; cognitive screening; quality indicators; health care ID SEVERE ALZHEIMERS-DISEASE; ACADEMY-OF-NEUROLOGY; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIALS; NURSING-HOME PLACEMENT; INAPPROPRIATE DRUG-USE; COGNITIVE IMPAIRMENT; DOUBLE-BLIND; STANDARDS SUBCOMMITTEE; PRACTICE PARAMETER C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RAND Hlth, Santa Monica, CA USA. WellPoint Inc, Programs CLin Excellence, Thousand Oaks, CA USA. RP Feil, DG (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 500 3-S,116-AE,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM denise.feil@med.va.gov NR 136 TC 23 Z9 23 U1 5 U2 8 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 2007 VL 55 SU 2 BP S293 EP S301 DI 10.1111/j.1532-5415.2007.01335.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400007 PM 17910550 ER PT J AU Fung, CH Spencer, B Eslami, M Crandall, C AF Fung, Constance H. Spencer, Benjamin Eslami, Michelle Crandall, Carolyn TI Quality indicators for the screening and care of urinary incontinence in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE urinary incontinence; quality of health care; quality indicators; health care ID OVERACTIVE BLADDER; NATURAL-HISTORY; INJECTION THERAPY; RISK-FACTORS; OLDER WOMEN; SYMPTOMS; HEALTH; EPIDEMIOLOGY; PREVALENCE; URGE C1 RAND Corp, Santa Monica, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Fung, CH (reprint author), 1776 Main St,POB 2138,M5S, Santa Monica, CA 90407 USA. EM cfung@rand.org NR 62 TC 9 Z9 10 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 2007 VL 55 SU 2 BP S443 EP S449 DI 10.1111/j.1532-5415.2007.01354.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400026 PM 17910569 ER PT J AU Gnanadesigan, N Fung, CH AF Gnanadesigan, Nallini Fung, Constance H. TI Quality indicators for screening and prevention in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE vulnerable elders; quality of health care; preventive health services; quality indicators; health care ID COMPREHENSIVE GERIATRIC ASSESSMENT; CORONARY-HEART-DISEASE; BRIEF PHYSICIAN ADVICE; CANADIAN TASK-FORCE; OLDER-ADULTS; PRIMARY-CARE; RECOMMENDATION STATEMENT; CONTROLLED-TRIALS; RANDOMIZED-TRIAL; ALCOHOL-PROBLEMS C1 Los Angeles Jewish Home Aging, Reseda, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RAND Hlth, Santa Monica, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Gnanadesigan, N (reprint author), 4322 Vanalden Ave, Tarzana, CA 91356 USA. EM nallini.desigan@gmail.com NR 75 TC 4 Z9 5 U1 3 U2 4 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 2007 VL 55 SU 2 BP S417 EP S423 DI 10.1111/j.1532-5415.2007.01350.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400022 PM 17910565 ER PT J AU Lorenz, KA Rosenfeld, K Wenger, N AF Lorenz, Karl A. Rosenfeld, Kenneth Wenger, Neil TI Quality indicators for palliative and end-of-life care in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Review DE quality of care; palliative care; evidence-based medicin; end-of-life care ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; ADVANCE DIRECTIVES; COMPLICATED GRIEF; ADVANCED CANCER; DYING PATIENTS; NURSING-HOME; LUNG-CANCER; INTENSIVE COMMUNICATION; SUSTAINING TREATMENTS C1 VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Vet Integrated Palliat Program, Los Angeles, CA 90064 USA. RAND Hlth, Santa Monica, CA USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. RP Lorenz, KA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Vet Integrated Palliat Program, 11301 Wilshire Blvd,Code 11-G, Los Angeles, CA 90064 USA. EM karl.lorenz@med.va.gov NR 101 TC 38 Z9 37 U1 1 U2 14 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 2007 VL 55 SU 2 BP S318 EP S326 DI 10.1111/j.1532-5415.2007.01338.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400010 PM 17910553 ER PT J AU Martin, JL Fung, CH AF Martin, Jennifer L. Fung, Constance H. TI Quality indicators for the care of sleep disorders in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sleep; sleep disorders; geriatrics; quality indicators ID LIMB MOVEMENT-DISORDER; RESTLESS LEGS SYNDROME; COGNITIVE-BEHAVIOR THERAPY; POSITIVE AIRWAY PRESSURE; LATE-LIFE INSOMNIA; OLDER-ADULTS; PRACTICE PARAMETERS; HEART HEALTH; CLINICAL-TRIAL; FOLLOW-UP C1 VA GLAHS GRECC, North Hills, CA 91343 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Gen Internal Med, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Martin, JL (reprint author), VA GLAHS GRECC, 11E,16111 Plummer St, North Hills, CA 91343 USA. EM jennifer.martin@va.gov FU NIA NIH HHS [AG10415] NR 57 TC 1 Z9 1 U1 1 U2 1 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 2007 VL 55 SU 2 BP S424 EP S430 DI 10.1111/j.1532-5415.2007.01351.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400023 PM 17910566 ER PT J AU Min, LC Mehrotra, R Fung, CH AF Min, Lillian C. Mehrotra, Rajnish Fung, Constance H. TI Quality indicators for the care of hypertension in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hypertension; quality indicators; aged ID RANDOMIZED CONTROLLED-TRIALS; ISOLATED SYSTOLIC HYPERTENSION; 2004 CANADIAN RECOMMENDATIONS; CONVERTING ENZYME-INHIBITORS; LEFT-VENTRICULAR HYPERTROPHY; CHRONIC KIDNEY-DISEASE; BLOOD-PRESSURE; HEART-FAILURE; CARDIOVASCULAR OUTCOMES; NONPHARMACOLOGIC INTERVENTIONS C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Med, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Min, LC (reprint author), 10945 Le Conte Ave,Suite 2338,Box 951687, Los Angeles, CA 90095 USA. EM lmin@mednet.ucla.edu FU NCRR NIH HHS [RR18298] NR 76 TC 8 Z9 8 U1 0 U2 1 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 2007 VL 55 SU 2 BP S359 EP S365 DI 10.1111/j.1532-5415.2007.01343.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400015 PM 17910558 ER PT J AU Watson, K Fung, CH Budoff, M AF Watson, Karol Fung, Constance H. Budoff, Matthew TI Quality indicators for the care of ischemic heart disease in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE ischemia; heart; age ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; TISSUE PLASMINOGEN-ACTIVATOR; LEFT-VENTRICULAR DYSFUNCTION; CONVERTING-ENZYME INHIBITOR; ESTROGEN PLUS PROGESTIN; ST-SEGMENT ELEVATION; SMOKING-CESSATION; CARDIAC REHABILITATION C1 Univ Calif Los Angeles, Med Ctr, Dept Cardiol, Div Cardiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Los Angeles, CA USA. Univ Calif Los Angeles, Harbor Med Ctr, Los Angeles, CA 90024 USA. RP Watson, K (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Cardiol, Div Cardiol, Box 951679,4780 MRL, Los Angeles, CA 90095 USA. EM KWatson@mednet.ucla.edu RI bashzar, salman/R-5748-2016 NR 78 TC 4 Z9 4 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 2007 VL 55 SU 2 BP S366 EP S372 DI 10.1111/j.1532-5415.2007.01344.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400016 PM 17910559 ER PT J AU Wenger, NS Roth, CP Shekelle, P AF Wenger, Neil S. Roth, Carol P. Shekelle, Paul CA ACOVE Investigators TI Introduction to the assessing care of vulnerable elders-3 quality indicator measurement set SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material DE quality of care; vulnerable elders; geriatric care measurement ID OLDER PATIENTS; HEALTH-CARE; OF-CARE; COMMUNITY; PEOPLE; ADULTS AB OBJECTIVES: To update and increase the comprehensiveness of the Assessing Care of Vulnerable Elders (ACOVE) set of process-of-care quality indicators (QIs) for the medical care provided to vulnerable elders and to keep up with the constantly changing medical literature, the QIs were revised and expanded. DESIGN: The ACOVE Clinical Committee expanded the number of measured conditions to 26 in the revised (ACOVE-3) set. For each condition, a content expert created potential QIs and, based on systematic reviews, developed a peer-reviewed monograph detailing each QI and its supporting evidence. Using these literature reviews, multidisciplinary panels of clinical experts participated in two rounds of anonymous ratings and a face-to-face group discussion to evaluate whether the QIs were valid measures of quality of care using a process that is an explicit combination of scientific evidence and professional consensus. The Clinical Committee evaluated the coherence of the complete set of QIs that the expert panels rated as valid. RESULTS: ACOVE-3 contains 392 QIs covering 14 different types of care processes (e.g., taking a medical history, performing a physical examination) and all four domains of care: screening and prevention (31% of QIs), diagnosis (20%), treatment (35%), and follow-up and continuity (14%). All QIs also apply to community-dwelling patients aged 75 and older. CONCLUSION: ACOVE-3 contains a set of QIs to comprehensively measure the care provided to vulnerable older persons at the level of the health system, health plan, or medical group. These QIs can be applied to identify areas of care in need of improvement and can form the basis of interventions to improve care. C1 RAND Hlth, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Wenger, NS (reprint author), RAND Hlth, 1776 Main St, Santa Monica, CA 90407 USA. EM nwenger@mednet.ucla.edu NR 28 TC 72 Z9 74 U1 1 U2 8 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 2007 VL 55 SU 2 BP S247 EP S252 DI 10.1111/j.1532-5415.2007.01328.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400001 PM 17910544 ER PT J AU Yueh, B Shekelle, P AF Yueh, Bevan Shekelle, Paul TI Quality indicators for the care of hearing loss in vulnerable elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hearing loss; hearing screening; mass screening; otolaryngology; audiology; hearing aids; cochlear implantation ID OLDER-ADULTS; OF-LIFE; COCHLEAR IMPLANTATION; COGNITIVE DYSFUNCTION; RANDOMIZED TRIAL; IMPAIRMENT; PREVALENCE; POPULATION; PEOPLE; AGE C1 Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Surg Perioperat Care Serv, Seattle, WA USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Dept Hlth Serv, Seattle, WA 98195 USA. Vet Affairs Ctr Regular Hlth Care Syst, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Yueh, B (reprint author), Univ Minnesota, Dept Otolaryngol Head & Neck Surg, MMC 396,420 Delaware St SE, Minneapolis, MN 55455 USA. EM byueh@umn.edu OI Yueh, Bevan/0000-0003-1380-1053 NR 51 TC 3 Z9 4 U1 0 U2 5 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 2007 VL 55 SU 2 BP S335 EP S339 DI 10.1111/j.1532-5415.2007.01340.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 218IY UT WOS:000250010400012 PM 17910555 ER PT J AU Haas, LB AF Haas, Linda B. TI Optimizing insulin use in type 2 diabetes: Role of basal and prandial insulin in long-term care facilities SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Review DE long-term care; oral antidiabetic drugs; insulin; type 2 diabetes mellitus ID GLYCEMIC CONTROL; NPH INSULIN; DOUBLE-BLIND; ELDERLY-PEOPLE; CLINICAL-TRIAL; ORAL-THERAPY; NURSING-HOME; WEIGHT-LOSS; MELLITUS; SULFONYLUREA C1 Univ Washington, Sch Nursing, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Haas, LB (reprint author), Univ Washington, Sch Nursing, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-118, Seattle, WA 98108 USA. EM Linda.Haas@va.gov NR 94 TC 23 Z9 23 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 2007 VL 8 IS 8 BP 502 EP 510 DI 10.1016/j.jamda.2007.08.002 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 223GP UT WOS:000250358200003 PM 17931573 ER PT J AU French, DD Campbell, RR Spehar, AM Rubenstein, LZ Cunningham, FE AF French, Dustin D. Campbell, Robert R. Spehar, Andrea M. Rubenstein, Laurence Z. Cunningham, Francesca E. TI Drug costs and use in VHA nursing homes: A national overview of long-stay residents SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE nursing homes; long-term care; drug costs; drug use; Medicare Part D; veterans AB Objectives: The aim of this study was to provide national annualized estimates of drug costs and use by drug classes for long-stay nursing home (NH) residents. Design: National, descriptive, secondary data analysis. Setting: National, Veterans Health Administration (VHA), 136 NHs. Participants: Our study population consisted of 6554 VHA long-stay NH residents, identified from the Minimum Data Set (MDS), who had an annual assessment during FY 2005 linked with 8,847,561 inpatient pharmacy claims. Measurement: Descriptive statistics of the annual drug costs and use by VHA therapeutic drug classes obtained from FY 2005 national pharmacy claims linked at the individual resident level. Results: The total cost of the drugs was $23,782,717 in 326 drug classes for 6554 VHA NH residents. Average annual drug cost was $3629 per resident (99% Confidence Interval [CI], $3343-$3915). The top 20 drug classes accounted for nearly 70% of total drug costs for long-stay NH residents. Approximately three quarters (73.3%) of these residents received a nonopioid analgesic (eg, acetaminophen, aspirin). Over half of these residents received antidepressants (selective serotonin reuptake inhibitors [SSRIs]) (54.3%), or other anti-infective drugs (eg, bacitracin, ciprofloxacin) (53.3%). Conclusions: This is the first national study of drug costs and use for long-stay veterans in VHA NHs. It is essential in any study analyzing drug costs and use in NH patients to differentiate long-stay residents from short-stay patients. This kind of detailed cost and use analysis has implications for projecting future costs associated with the Medicare Part D prescription benefit for dually eligible NH residents. C1 James A Haley Vet Adm Med Ctr, VISN Patient Safety Ctr Inquiry 8, Tampa, FL 33612 USA. Univ Calif Los Angeles, David Geffen Sch Med, Sepulveda, CA USA. GRECC, VA Greater Los Angeles Healthcare System, Tampa, FL USA. W Los Angeles Div, North Hills, CA USA. Univ Illinois Chicago, Hines, IL USA. VHA Ctr Medicat Safety Pharm Benefits Management, Hines, IL USA. RP French, DD (reprint author), James A Haley Vet Adm Med Ctr, VISN Patient Safety Ctr Inquiry 8, 13000 Bruce B Downs Blvd,118M, Tampa, FL 33612 USA. EM Dustin.French@va.gov OI French, Dustin/0000-0003-4064-3206 NR 16 TC 5 Z9 5 U1 0 U2 3 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 2007 VL 8 IS 8 BP 515 EP 518 DI 10.1016/j.jamda.2007.02.001 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 223GP UT WOS:000250358200005 PM 17931575 ER PT J AU O'Hare, AM Choi, AI Bertenthal, D Bacchetti, P Garg, AX Kaufman, JS Walter, LC Mehta, KM Steinman, MA Allon, M McClellan, WM Landefeld, CS AF O'Hare, Ann M. Choi, Andy I. Bertenthal, Daniel Bacchetti, Peter Garg, Amit X. Kaufman, James S. Walter, Louise C. Mehta, Kala M. Steinman, Michael A. Allon, Michael McClellan, William M. Landefeld, C. Seth TI Age affects outcomes in chronic kidney disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; BLOOD-PRESSURE; RISK; POPULATION; COHORT; CARE; MEN; STRATIFICATION; INSUFFICIENCY; PROGRESSION AB Chronic kidney disease (CKD) is common among the elderly. However, little is known about how the clinical implications of CKD vary with age. We examined the age-specific incidence of death, treated end-stage renal disease (ESRD), and change in estimated glomerular filtration rate (eGFR) among 209,622 US veterans with CKD stages 3 to 5 followed for a mean of 3.2 years. Patients aged 75 years or older at baseline comprised 47% of the overall cohort and accounted for 28% of the 9227 cases of ESRD that occurred during follow-up. Among patients of all ages, rates of both death and ESRD were inversely related to eGFR at baseline. However, among those with comparable levels of eGFR, older patients had higher rates of death and lower rates of ESRD than younger patients. Consequently, the level of eGFR below which the risk of ESRD exceeded the risk of death varied by age, ranging from 45 ml/min per 1.73 m(2) for 18 to 44 year old patients to 15 ml/min per 1.73 m(2) for 65 to 84 year old patients. Among those 85 years or older, the risk of death always exceeded the risk of ESRD in this cohort. Among patients with eGFR levels <45 ml/min per 1.73 m(2) at baseline, older patients were less likely than their younger counterparts to experience an annual decline in eGFR of >3 ml/min per 1.73 m(2). In conclusion, age is a major effect modifier among patients with an eGFR of <60 ml/min per 1.73 m(2), challenging us to move beyond a uniform stage-based approach to managing CKD. C1 Univ Washington, Dept Med, VA Puget Sound Healthcare Syst, Div Nephrol, Seattle, WA 98108 USA. VA Med Ctr San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. VA San Francisco, VA San Francisco Hlth Serv Res, San Francisco, CA USA. VA San Francisco, Dev Res Enhacement Award Program, San Francisco, CA USA. Univ Western Ontario, Div Nephrol, London, ON, Canada. VA Boston Healthcare Syst, Renal Sect, Boston, MA USA. Univ Alabama, Div Nephrol, Birmingham, AL USA. Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA USA. RP O'Hare, AM (reprint author), Univ Washington, Dept Med, VA Puget Sound Healthcare Syst, Div Nephrol, Bldg 100 Room 5B113,1660 S Columbian Way, Seattle, WA 98108 USA. EM ann.ohare@va.gov FU NIA NIH HHS [AG000912, K23 AG28980-01]; NIDDK NIH HHS [K24-DK59818-01] NR 28 TC 272 Z9 283 U1 0 U2 7 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 2007 VL 18 IS 10 BP 2758 EP 2765 DI 10.1681/ASN.2007040422 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 231YU UT WOS:000250985900019 PM 17855638 ER PT J AU Mehrotra, R Kermah, D Fried, L Kalantar-Zadeh, K Khawar, O Norris, K Nissenson, A AF Mehrotra, Rajnish Kermah, Dulcie Fried, Linda Kalantar-Zadeh, Kamyar Khawar, Osman Norris, Keith Nissenson, Allen TI Chronic peritoneal dialysis in the United States: Declining utilization despite improving outcomes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Nephrology CY NOV 14-19, 2006 CL San Diego, CA SP Amer Soc Nephrol ID STAGE RENAL-DISEASE; ESRD PATIENTS; MODALITY SELECTION; PATIENT; HEMODIALYSIS; SURVIVAL; CHOICE AB In the United States, chronic peritoneal dialysis take-on has declined among incident ESRD patients. Although increasing age, co-morbidity, and body size may explain part of this decline, other factors likely contribute. Among incident ESRD patients in the United States, we found that peritoneal dialysis take-on significantly decreased from 11% in 1996 to 1997 to 7% in 2002 to 2003 (P < 0.001 for the trend). This decrease remained after adjusting for patient demographics, case-mix, and laboratory data, suggesting the involvement of other factors. This decline in utilization occurred during a time of improving outcomes for incident peritoneal dialysis patients, measured as reduced hazards for death or for the need to transfer to hemodialysis. In contrast, among patients initially treated with hemodialysis, the 12-month adjusted hazards for death or transfer to peritoneal dialysis slightly worsened or were unchanged over this same period. Therefore, the decline in peritoneal dialysis take-on cannot be entirely explained by increasing age, co-morbidity and body size of incident ESRD patients. The decline in utilization has occurred at a time when the early outcomes of CPD patients have improved. C1 Harbor UCLA Med Ctr, Loa Angeles Biomed Res Inst, Torrance, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Charles Drew Univ, Los Angeles, CA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Mehrotra, R (reprint author), 1124 W Carson St, Torrance, CA 90502 USA. EM rmehrotra@labiomed.org OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 FU NCRR NIH HHS [RR11145, RR14616, RR18298, RR03026]; NIMHD NIH HHS [MD00148] NR 22 TC 88 Z9 89 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2007 VL 18 IS 10 BP 2781 EP 2788 DI 10.1681/ASN.2006101130 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 231YU UT WOS:000250985900022 PM 17804675 ER PT J AU Ramlawi, B Otu, H Rudolph, JL Mieno, S Kohane, IS Can, H Libermann, TA Marcantonio, ER Bianchi, C Sellke, FW AF Ramlawi, Basel Otu, Hasan Rudolph, James L. Mieno, Shigetoshi Kohane, Isaac S. Can, Handan Libermann, Towia A. Marcantonio, Edward R. Bianchi, Cesario Sellke, Frank W. TI Genomic expression pathways associated with brain injury after cardiopulmonary bypass SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID CARDIAC-SURGERY; GRAFT-SURGERY; INFLAMMATORY RESPONSE; COGNITIVE DYSFUNCTION; OUTCOMES; ACTIVATION; OPERATION; DISEASE AB Objectives: Neurologic injury after cardiac surgery, often manifested as neurocognitive decline, is a common postoperative complication without clear cause. We studied acute variations in gene-expression profiles of patients with neurocognitive decline (NCD group) compared with those without neurocognitive decline (NORM group) after cardiopulmonary bypass. Methods: Forty-two patients undergoing coronary artery bypass grafting, valve procedures, or both by using cardiopulmonary bypass were administered a validated neurocognitive battery preoperatively and postoperatively at day 4. Neurocognitive decline was defined as 1 standard deviation from baseline on 25% or greater of tasks. Whole-blood mRNA was isolated preoperatively and at 6 hours after surgical intervention for fold-change calculation. Relative gene expression in the NCD versus the NORM group was assessed by using Affymetrix GeneChip U133 Plus 2.0 (> 40,000 genes) from mRNA samples collected. Differential expression, clustering, gene ontology, and canonical pathway analysis were performed. Validation of microarray gene expression was performed with SYBR Green real-time polymerase chain reaction. Results: Patients with neurocognitive decline (17/42 [40.5%] patients) were associated with a significantly different gene-expression response compared with that of healthy patients. Compared with preoperative samples, 6-hour samples had 531 upregulated and 670 downregulated genes uniquely in the NCD group compared with 2214 upregulated and 558 downregulated genes uniquely in the NORM group (P < .001; lower confidence bound, >= 1.2). Compared with patients in the NORM group, patients with neurocognitive decline had significantly different gene-expression pathways involving inflammation ( including FAS, IL2RB, and CD59), antigen presentation (including HLA-DQ1, TAP1, and TAP2), and cellular adhesion (including ICAM2, ICAM3, and CAD7) among others. Conclusions: Patients with neurocognitive decline have inherently different genetic responses to cardiopulmonary bypass compared with those of patients without neurocognitive decline Genetic variations in inflammatory, cell adhesion, and apoptotic pathways might be important contributors to the pathophysiology of neurologic injury after cardiopulmonary bypass and could become a target for prevention and risk stratification. C1 Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Genom Ctr, Boston, MA 02215 USA. Childrens Hosp, Informat Program, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Ctr Geriatr Res Educ & Clin, Boston, MA 02115 USA. RP Sellke, FW (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, LMOB 2A,110 Francis St, Boston, MA 02215 USA. EM fsellke@caregroup.harvard.edu RI Libermann, Towia/F-9866-2010; Kohane, Isaac Kohane/K-3716-2012; bianchi, cesario/H-6238-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Libermann, Towia/0000-0002-4006-8179; Otu, Hasan/0000-0002-9253-8152 FU NHLBI NIH HHS [T35 HL094308, HL-46716, HL04095-06, R01 HL046716] NR 33 TC 11 Z9 11 U1 1 U2 1 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 2007 VL 134 IS 4 BP 996 EP U71 DI 10.1016/j.jtcvs.2007.01.096 PG 14 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 215IB UT WOS:000249800600026 PM 17903520 ER PT J AU Zhang, P Guccione, JM Nicholas, SI Walker, JC Crawford, PC Shamal, A Acevedo-Bolton, G Guttman, MA Ozturk, C McVeigh, ER Saloner, DA Wallace, AW Ratcliffe, MB AF Zhang, Peng Guccione, Julius M. Nicholas, Susan I. Walker, Joseph C. Crawford, Philip C. Shamal, Amin Acevedo-Bolton, Gabriel Guttman, Michael A. Ozturk, Cengizhan McVeigh, Elliot R. Saloner, David A. Wallace, Arthur W. Ratcliffe, Mark B. TI Endoventricular patch plasty for dyskinetic anteroapical left ventricular aneurysm increases systolic circumferential shortening in sheep SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID VOLUME REDUCTION SURGERY; FINITE-ELEMENT-ANALYSIS; MECHANICAL DYSFUNCTION; BORDER ZONE; MR-IMAGES; MODEL; RESTORATION; CARDIOMYOPATHY; RECONSTRUCTION; MYOCARDIUM AB Objective: Endoventricular patch plasty ( Dor procedure) has gained favor as a surgical treatment for heart failure associated with large anteroapical myocardial infarction. We tested the hypotheses that the Dor procedure increases systolic circumferential shortening and longitudinal shortening in noninfarcted left ventricular regions in sheep. Methods: In 6 male Dorsett sheep, the left anterior descending coronary artery and its second diagonal branch were ligated 40% of the distance from the apex to the base. Sixteen weeks after myocardial infarction, a Dor procedure was performed with a Dacron patch that was 50% of the infarct neck dimension. Two weeks before and 2 and 6 weeks after the Dor procedure, animals underwent magnetic resonance imaging with tissue tagging in multiple short- axis and long- axis slices. Fully three- dimensional strain analyses were performed. All 6 end- systolic strain components were compared in regions 1 cm, 2 cm, 3 cm, and 4 cm below the valves, as well as in the anterior, posterior, and lateral left ventricular walls and the interventricular septum. Results: Circumferential shortening increased from before the Dor procedure to 6 weeks after repair in nearly every left ventricular region ( 13/ 16). The greatest regional change in circumferential shortening was found in the equatorial region or 2 cm below the base and in the posterior wall ( from 9.0% to 18.4%; P <.0001). Longitudinal shortening increased 2 weeks after the Dor procedure but then returned near baseline by 6 weeks after the Dor procedure. Conclusion: The Dor procedure significantly increases systolic circumferential shortening in nearly all noninfarcted left ventricular regions in sheep. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Dept Vet Affairs Med Ctr, San Francisco, CA USA. NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA. RP Guccione, JM (reprint author), San Francisco VA Med Ctr, Div Surg Serv, 4150 Clement St, San Francisco, CA 94121 USA. EM julius.guccione@med.va.gov RI Ozturk, Cengizhan/A-6177-2016 OI Ozturk, Cengizhan/0000-0002-6966-0774 FU NHLBI NIH HHS [R01 HL063348-01A1, R01 HL063348, R01 HL077921, R01 HL077921-01A2, R01-HL-63348, R01-HL-77921] NR 32 TC 21 Z9 23 U1 0 U2 0 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 2007 VL 134 IS 4 BP 1017 EP U80 DI 10.1016/j.jtcvs.2007.03.060 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 215IB UT WOS:000249800600029 PM 17903523 ER PT J AU Friedman, MJ Pitman, RK AF Friedman, Matthew J. Pitman, Roger K. TI New findings on the neurobiology of posttraurnatic stress disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Editorial Material C1 Natl Ctr PTSD, Dept Vet Affairs, White River Jct, VT 05009 USA. Dartmouth Med Sch, Dept Psychiat & Pharmacol, Lebanon, NH USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Friedman, MJ (reprint author), Natl Ctr PTSD, Dept Vet Affairs, 215 N Main St, White River Jct, VT 05009 USA. EM Matthew.Friedman@Dartmouth.edu NR 11 TC 2 Z9 2 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2007 VL 20 IS 5 BP 653 EP 655 DI 10.1002/jts.20299 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 228NK UT WOS:000250736400001 PM 17955528 ER PT J AU Carson, MA Metzger, LJ Lasko, NB Paulus, LA Morse, AE Pitman, RK Orr, SP AF Carson, Margaret A. Metzger, Linda J. Lasko, Natasha B. Paulus, Lynn A. Morse, Amanda E. Pitman, Roger K. Orr, Scott P. TI Physiologic reactivity to startling tones in female Vietnam nurse veterans with PTSD SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; LOUD TONES; TRAUMA SURVIVORS; ACOUSTIC STARTLE; RESPONSES; REFLEX; SCALE; WOMEN AB Posttraumatic stress disorder (PTSD) is associated with larger heart rate (HR), skin conductance (SC), and eyeblink responses to sudden, loud tones. The present study tested this association in female nurse veterans with PTSD related to witnessing patients' death, severe injury and/or suffering during their Vietnam service. Nurses with current, past but not current, or who never had PTSD listened to 15 consecutive 95-dB, 500-ms, 1000-Hz tones with sudden onsets, while HR, SC and eyeblink responses were measured. Nurses with current PTSD produced significantly larger averaged HR, but not SC or eyeblink responses across tone trials. A larger HR response to loud tones is one of the most robust physiologic findings in PTSD and may reflect increased defensive responding. C1 St Anselm Coll, Dept Nursing, Manchester, NH 03102 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. VA Med Ctr, Manchester, NH USA. Concord Hosp, Concord, NH USA. RP Carson, MA (reprint author), St Anselm Coll, Dept Nursing, 100 St Anselm Dr, Manchester, NH 03102 USA. EM mcarson@anselm.edu NR 34 TC 19 Z9 19 U1 6 U2 6 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 2007 VL 20 IS 5 BP 657 EP 666 DI 10.1002/jts.20218 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 228NK UT WOS:000250736400002 PM 17955532 ER PT J AU Shin, LM Bush, G Whalen, PJ Handwerger, K Cannistraro, PA Wright, CL Mattis, B Macklin, ML Lasko, NB Orr, SP Pitman, RK Rauch, SL AF Shin, Lisa M. Bush, George Whalen, Paul J. Handwerger, Kathryn Cannistraro, Paul A. Wright, Christopher L. Mattis, Brian Macklin, Michael L. Lasko, Natasha B. Orr, Scott P. Pitman, Roger K. Rauch, Scott L. TI Dorsal anterior cingulate function in posttraumatic stress disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID CHILDHOOD SEXUAL-ABUSE; SCRIPT-DRIVEN IMAGERY; POSITRON-EMISSION-TOMOGRAPHY; CORTICOLIMBIC BLOOD-FLOW; PREFRONTAL CORTEX; VIETNAM VETERANS; COUNTING STROOP; PTSD; INFORMATION; MEMORY AB Previous neuroimaging research has shown diminished anterior cingulate cortex (ACC) function in posttraumatic stress disorder (PTSD), with most of these findings occurring in pregenual/subgenual ACC. This study investigates whether dorsal ACC (dACC) function is also diminished in PTSD. The authors used functional magnetic resonance imaging to study dACC function during the performance of the counting Stroop. Thirteen men with PTSD and 13 trauma-exposed men without PTSD participated. In the interference-neutral comparison, both groups showed response time increases and dACC activations. These results suggest that dACC function in PTSD is not diminished during the performance of this nonemotional task. In fact, there were statistical trends in the opposite direction. These findings will help to better characterize functional brain abnormalities in this disorder. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dartmouth Coll, Dept Psychol, Hanover, NH 03755 USA. Brigham & Womens Hosp, Dept Neurol, Brigham Behav Neurol Grp, Boston, MA 02115 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. VA Res Serv, Manchester, NH USA. RP Shin, LM (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM lisa.shin@tufts.edu FU NIMH NIH HHS [MH-54636, MH-60219, MH64806] NR 64 TC 38 Z9 38 U1 3 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2007 VL 20 IS 5 BP 701 EP 712 DI 10.1002/jts.20231 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 228NK UT WOS:000250736400006 PM 17955522 ER PT J AU Yehuda, R Morris, A Labinsky, E Zemelman, S Schmeidler, J AF Yehuda, Rachel Morris, Adam Labinsky, Ellen Zemelman, Shelly Schmeidler, James TI Ten-year follow-up study of cortisol levels in aging holocaust survivors with and without PTSD SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; EXCRETION; SYMPTOMS; SYSTEM AB To investigate the longitudinal course of mean 24-hour urinary cortisol excretion in posttraumatic stress disorder (PTSD), the authors evaluated 24-hour cortisol excretion in 28 Holocaust survivors 10 years after obtaining an initial estimate. Cortisol levels increased in participants whose PTSD had remitted (n = 3) but declined in participants who developed PTSD (n = 3) or whose PTSD status did not change over time (PTSD+: n = 14, PTSD-: n = 8). Cortisol levels at Time I predicted diagnostic status change better than psychological variables, including exposure to traumatic events between assessments. The authors conclude that cortisol levels are affected by change in PTSD status and age. C1 Mt Sinai Sch Med, Dept Psychiat, Div Traumat Stress Studies, Bronx, NY USA. James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Yehuda, R (reprint author), Vet Adm Med Ctr, Psychiat OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rachei.yehuda@med.va.gov FU NCRR NIH HHS [5 M01 RR00071]; NIMH NIH HHS [R01 MH64675-01] NR 16 TC 31 Z9 33 U1 2 U2 4 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 2007 VL 20 IS 5 BP 757 EP 761 DI 10.1002/jts.20228 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 228NK UT WOS:000250736400011 PM 17955524 ER PT J AU Woodward, SH Kaloupek, DG Streeter, CC Kimble, MO Reiss, AL Eliez, S Wald, LL Renshaw, PE Frederick, BB AF Woodward, Steven H. Kaloupek, Danny G. Streeter, Chris C. Kimble, Matthew O. Reiss, Allan L. Eliez, Stephan Wald, Lawrence L. Renshaw, Perry E. Frederick, Blaise B. TI Brain, skull, and cerebrospinal fluid volumes in adult Posttraumatic stress disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID SMALLER HIPPOCAMPAL VOLUME; ADVERSE CHILDHOOD EXPERIENCES; WHITE-MATTER VOLUME; HEAD CIRCUMFERENCE; NUTRITIONAL-STATUS; CHRONIC-ALCOHOLICS; COMBAT VETERANS; RISK-FACTORS; CHILDREN; INTELLIGENCE AB Children and adolescents with maltreatment-related posttraumatic stress disorder (PTSD) exhibit smaller intracranial tissue volume than controls. Linear relationships have also been observed between intracranial tissue volume and the age of maltreatment onset. The authors explored associations among adult PTSD, early trauma, and cerebral volumes in 99 combat veterans. A bone-based estimate of cranial volume was developed to adjust for variation in body size. Posttraumatic stress disorder was not associated with smaller cerebral tissue volume, but rather with smaller cerebrospinal fluid (CSF) and cranial volumes. These findings co-occurred with expected effects of alcoholism and aging on cerebral tissue and CSF volumes. The results point to early developmental divergences between groups with and without PTSD following adult trauma. C1 Natl Ctr PTSD, Clin Lab & Educ Div, Menlo Pk, CA 94025 USA. VA Palo Alto Healthcare Syst, Psychol Serv, Palo Alto, CA USA. VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Div Psychiat, Boston, MA 02215 USA. Middlebury Coll, Dept Psychol, Middlebury, VT 05753 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Univ Geneva, Dept Psychiat, Geneva, Switzerland. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Woodward, SH (reprint author), Natl Ctr PTSD, Clin Lab & Educ Div, Mail Code 334 PTSD VA Palo Alto HCS,795 Willow Rd, Menlo Pk, CA 94025 USA. EM Steve.woodward@med.va.gov RI Frederick, Blaise/G-6098-2012; Wald, Lawrence/D-4151-2009; OI Frederick, Blaise/0000-0001-5832-5279; Kaloupek, Danny/0000-0002-0795-593X FU NIAAA NIH HHS [K23AA13149] NR 48 TC 13 Z9 13 U1 2 U2 5 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 2007 VL 20 IS 5 BP 763 EP 774 DI 10.1002/jts.20241 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 228NK UT WOS:000250736400012 PM 17955544 ER PT J AU Sonis, J King, DW King, LA Lauterbach, D Palmieri, P AF Sonis, Jeffrey King, Daniel W. King, Lynda A. Lauterbach, Dean Palmieri, Patrick TI Innovations in trauma research methods, 2006 SO JOURNAL OF TRAUMATIC STRESS LA English DT Editorial Material C1 Univ N Carolina, Sch Med, Dept Social Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Family Med, Chapel Hill, NC 27599 USA. Boston Univ, Dept Psychiat, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. Eastern Michigan Univ, Dept Psychol, Ypsilanti, MI 48197 USA. Kent State Univ, Dept Psychiat, Summa Hlth Syst, Kent, OH 44242 USA. Kent State Univ, Dept Psychol, Kent, OH 44242 USA. RP Sonis, J (reprint author), Univ N Carolina, Sch Med, Dept Social Med, Wing D,CB 7240, Chapel Hill, NC 27599 USA. EM jsonis@med.unc.edu FU NIMH NIH HHS [5 R13 MH068798-04] NR 4 TC 0 Z9 0 U1 0 U2 0 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 2007 VL 20 IS 5 BP 775 EP 777 DI 10.1002/jts.20293 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 228NK UT WOS:000250736400013 PM 17955547 ER PT J AU Barber, JP Triffleman, E Marmar, C AF Barber, Jacques P. Triffleman, Elisa Marmar, Charles TI Considerations in treatment integrity: Implications and recommendations for PTSD research SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT Conference on Innovations in Trauma Research Methods CY NOV 03-04, 2006 CL Hollywood, CA ID POSTTRAUMATIC-STRESS-DISORDER; COLLABORATIVE-COCAINE-TREATMENT; COGNITIVE-PROCESSING THERAPY; RANDOMIZED CONTROLLED-TRIAL; IMAGINAL EXPOSURE; PROLONGED EXPOSURE; SEEKING-SAFETY; TRAUMA THERAPY; CLINICAL-TRIAL; BATTERED WOMEN AB In this article, the authors address the rationale for and uses of treatment integrity measurement in psychotherapy research, focusing on therapists' adherence and competence in trauma and posttraumatic stress disorder treatment research. The following issues are examined: (a) distinctions between adherence monitoring, performed contemporaneously with ongoing study treatments, and adherence evaluation, and the implications for outcomes analysis; (b) simultaneous measurement of adherence and competence, (c) selection of sessions for adherence/competence assessment and the need for concurrent outcome measurement, and (d) the association between therapist adherence, competence, alliance and treatment outcome. Recommendations regarding common problems in the implementation of adherence and competence measurement are made throughout. The article concludes with a summary of steps and considerations in decision-making with regard to treatment integrity. C1 Univ Penn, Sch Med, Dept Psychiat, Ctr Psychotherapy Res, Philadelphia, PA 19104 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Barber, JP (reprint author), Univ Penn, Sch Med, Dept Psychiat, Ctr Psychotherapy Res, Suite 648,3535 Market St, Philadelphia, PA 19104 USA. EM Barberj@mail.med.upenn.edu FU NIMH NIH HHS [MH 061410, MH 070664] NR 44 TC 25 Z9 25 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 2007 VL 20 IS 5 BP 793 EP 805 DI 10.1002/jts.20295 PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 228NK UT WOS:000250736400015 PM 17955529 ER PT J AU Hermos, JA Young, MM Lawler, EV Rosenbloom, D Fiore, LD AF Hermos, John A. Young, Melissa M. Lawler, Elizabeth V. Rosenbloom, David Fiore, Louis D. TI Long-term, high-dose benzodiazepine prescriptions in veteran patients with PTSD: Influence of preexisting alcoholism and drug-abuse diagnoses SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; THERAPY AB Databases from the New England Veterans Integrated Service Network were analyzed to determine factors associated with long-term, high-dose anxiolytic benzodiazepine prescriptions dispensed to patients with posttraumatic stress disorder (PTSD) and existing alcoholism and/or drug abuse diagnoses. Among 2,183 PTSD patients, 234 received the highest 10% average daily doses for alprazolam, clonazepam, diazepam, or lorazepam, doses above those typically recommended. Highest doses were more commonly prescribed to patients with existing drug abuse diagnoses. Among patients with PTSD and alcoholism, younger age, drug abuse, and concurrent prescriptions for another benzodiazepine and oxycodone/acetaminophen independently predicted high doses. Results indicare that for veteran patients with PTSD, alcoholism alone is not associated with high-dose benzodiazepines, but existing drug abuse diagnoses do increase that risk. C1 VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr 15, Pharmacoepidemiol Res Grp, Boston, MA 02130 USA. Boston Univ, Sch Publ Hlth, Youth Alcohol Prevent Ctr, Dept Social & Behav Sci, Boston, MA 02215 USA. RP Hermos, JA (reprint author), VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr 15, Pharmacoepidemiol Res Grp, 150 S Huntington Ave, Boston, MA 02130 USA. EM john.hermos@med.va.gov NR 15 TC 9 Z9 9 U1 0 U2 4 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 2007 VL 20 IS 5 BP 909 EP 914 DI 10.1002/jts.20254 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 228NK UT WOS:000250736400025 PM 17955537 ER PT J AU Weathers, EW Keane, IA AF Weathers, E. W. Keane, I. A. TI The crucial role of criterion A: A response to Maier's commentary SO JOURNAL OF TRAUMATIC STRESS LA English DT Editorial Material AB We thank Maier for his thoughtful comments (this issue, pp. 925-926) and appreciate the opportunity to further explicate our views regarding the Criterion A problem. According to Maier, the obvious conclusion to he drawn from our article (Weathers & Keane, 2007) is that Criterion A should be eliminated. We believe the opposite, given the current conceptual and empirical status of the posttraumatic stress disorder (PTSD) construct. C1 VA Boston Healthcare Syst, Res Serv 151, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Boston, MA 02215 USA. Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. RP Weathers, EW (reprint author), VA Boston Healthcare Syst, Res Serv 151, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM terry.keane@va.gov NR 8 TC 2 Z9 2 U1 0 U2 0 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 2007 VL 20 IS 5 BP 917 EP 919 DI 10.1002/jts.20297 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 228NK UT WOS:000250736400027 ER PT J AU Scales, CD Presti, JC Kane, CJ Terris, MK Aronson, WJ Amling, CL Freedland, SJ AF Scales, Charles D., Jr. Presti, Joseph C., Jr. Kane, Christopher J. Terris, Martha K. Aronson, William J. Amling, Christopher L. Freedland, Stephen J. CA SEARCH Database Study Grp TI Predicting unilateral prostate cancer based on biopsy features: Implications for focal ablative therapy-results from the SEARCH database SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; biopsy; prostatectomy ID RADICAL PROSTATECTOMY; UROLOGY LITERATURE; GLEASON SCORE; NEEDLE-BIOPSY; ANTIGEN ERA; SPECIMENS; ACCURACY; GRADE; CARCINOMA AB Purpose: For men with low risk prostate cancer it was recently proposed that ablative treatment to the affected side may decrease morbidity, while maintaining good oncological outcomes. However, few studies have assessed the correlation between biopsy parameters and pathological outcome (unilateral vs bilateral disease). Materials and Methods: Using the Shared Equal Access Regional Cancer Hospital Database of men treated with radical prostatectomy at multiple equal access medical centers we retrospectively examined the records of 261 men with clinical stage T1c or T2a prostate cancer, prostate specific antigen less than 10 ng/ml, Gleason sum 6 or less and only 1 or 2 ipsilateral positive cores on at least sextant biopsy. We compared clinical characteristics between men with pathologically unilateral disease or less (pT2b or less) and men with pathologically bilateral disease or extraprostatic extension (pT2c or greater). To determine the significant predictors of pT2c or greater disease we used a multivariate logistic regression model. Results: Of the cohort of 261 men with low risk prostate cancer only 93 (35.1%) had unilateral or no evidence of disease following examination of radical prostatectomy specimens. Men with pathologically unilateral or less disease did not differ from those with bilateral or more advanced disease by age, prostate specific antigen, clinical stage, body mass index or number of positive biopsy cores (1 vs 2). On multivariate analysis no clinical feature was significantly related to pathologically unilateral or less vs bilateral or greater disease. Conclusions: The majority of men with low risk prostate cancer and 1 or 2 ipsilateral positive biopsy cores have pathologically bilateral disease. Therefore, strategies for unilateral treatment of prostate cancer are unlikely to be curative for these men. C1 Duke Univ, Med Ctr, Div Urol Surg, Dept Surg,Sch Med, Durham, NC 27710 USA. Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Sch Med, Duke Prostate Ctr, Durham, NC 27710 USA. Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. Stanford Univ, Dept Urol, Sch Med, Palo Alto, CA 94304 USA. Vet Affairs Med Ctr, Urol Sect, Dept Surg, Palo Alto, CA 94304 USA. Vet Affairs Med Ctr, Urol Sect, Dept Surg, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Urol, Sch Med, Los Angeles, CA USA. Med Coll Georgia, Urol Sect, Augusta, GA USA. Vet Affairs Med Ctr, Augusta, GA USA. Univ Alabama, Dept Urol, Birmingham, AL USA. RP Freedland, SJ (reprint author), Duke Univ, Med Ctr, Div Urol Surg, Dept Surg,Sch Med, Box 2626, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [R01CA100938, P50 CA92131-01A1] NR 19 TC 41 Z9 42 U1 0 U2 2 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 2007 VL 178 IS 4 BP 1249 EP 1252 DI 10.1016/j.juro.2007.05.151 PN 1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 212BI UT WOS:000249568200030 PM 17698131 ER PT J AU Dahl, DM Rassweiler, J AF Dahl, Douglas M. Rassweiler, Jens TI Combined inguinal hernia repair with prosthetic mesh during transperitoneal robot assisted laparoscopic radical prostatectomy: A 4-year experience - Comments SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02115 USA. Univ Heidelberg, SLK Klin Heilbronn, Dept Urol, Heilbronn, Germany. RP Dahl, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2007 VL 178 IS 4 BP 1299 EP 1300 DI 10.1016/j.juro.2007.05.350 PN 1 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 212BI UT WOS:000249568200044 ER PT J AU Shao, TC Li, H Ittmann, M Cunningham, GR AF Shao, T. C. Li, H. Ittmann, M. Cunningham, G. R. TI Effects of dutasteride on prostate growth in the large probasin-large T antigen mouse model of prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; dutasteride; mice; transgenic; prostatic hyperplasia; prostatic neoplasms ID 5-ALPHA-REDUCTASE INHIBITOR; VENTRAL PROSTATE; FINASTERIDE; HYPERPLASIA; MEN; TYPE-1; RATS; CHEMOPREVENTION; APOPTOSIS; EFFICACY AB Purpose: We evaluated the effects of dutasteride for preventing or delaying prostate growth and neoplastic changes in a transgenic model of prostate cancer. Materials and Methods: Large probasin-large T antigen mice were treated for 4 or 8 weeks with dutasteride. The prostate and seminal vesicles were compared with those from intact and castrated large probasin-large T antigen mice and WT mice. Results: Dutasteride greatly decreased the transgene induced increase in prostate weight but castration caused greater reduction. Dutasteride inhibited type I and 2, 5alpha-reductase activities, decreased DNA and protein, and increased apoptotic bodies and TUNEL staining in the dorsolateral prostate. No evidence of poorly differentiated cancer was seen. Dutasteride did not decrease the weight of the androgen dependent levator ani or bulbocavernosus muscle. Conclusions: Dutasteride inhibited type 1 and 2, 5alpha-reductase activities, and decreased DNA and protein content of the dorsolateral. prostate without affecting androgen responsive muscle weight in large probasin-large T antigen mice. These studies provide support for the hypothesis that a 5alpha-reductase inhibitor inhibits the initiation and/or progression of clinical prostate cancers. C1 Michael E DeBakey Vet Affairs Med Ctr, Res Serv 151, Dept Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Cunningham, GR (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Res Serv 151, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 19 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2007 VL 178 IS 4 BP 1521 EP 1527 DI 10.1016/j.juro.2007.05.118 PN 1 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 212BI UT WOS:000249568200094 PM 17707058 ER PT J AU Conrad, MF Crawford, RS Pedraza, JD Brewster, DC LaMuraglia, GM Corey, M Abbara, S Cambria, RP AF Conrad, Mark F. Crawford, Robert S. Pedraza, Juan D. Brewster, David C. LaMuraglia, Glenn M. Corey, Michael Abbara, Sulmy Cambria, Richard P. TI Long-term durability of open abdominal aortic aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 22-24, 2006 CL Boston, MA SP New England Soc Vasc Surg ID RANDOMIZED CONTROLLED-TRIAL; ENDOVASCULAR REPAIR; SECONDARY INTERVENTIONS; UNITED-STATES; OPEN SURGERY; EXPERIENCE; OUTCOMES; COMPLICATIONS; POPULATION; EUROSTAR AB Objective: In multiple comparisons of open vs endovascular (EVAR) repair of abdominal aortic aneurysms, the prior assumption that open repair produced superior durability has been challenged by advocates of EVAR. Although focus on EVAR reintervention has been intense, few contemporary studies document late outcomes after open repair; this was the goal of this study. Methods: From January 1994 to December 1998 (chosen to ensure a minimum 5-year follow-up), 540 patients underwent elective open repair. Surveillance imaging (computed tomographic and magnetic resonance imaging scans) was obtained for 152 (57%) of the 269 patients who remained alive at a mean follow-up of 87 months. Study end points included freedom from graft-related interventions and aneurysm-related and overall survival (Kaplan-Meier test); factors predictive of these end points were determined by multivariate analysis. Results: The mean age at operation was 73 years. A total of 76% of patients were male; 11% had renal insufficiency (creatinine >= 1.5 mg/dL), and 13% had chronic obstructive pulmonary disease. The aortic cross-clamp position was suprarenal in 135 (25%) patients, and 284 (53%) of patients had bifurcated grafts placed. Operative mortality (30 days) was 3%, and the median length of hospital stay was 7 days. Postoperative complications occurred in 68 (13%) patients. Predictors of postoperative complications included a history of myocardial infarction (hazard ratio [HR], 2.0; P =.01) and renal insufficiency (HR, 2.5; P =.02). The mean follow-up for all patients was 87 months. Actuarial survival was 70.7% +/- 2% and 44.3% +/- 2.4% at 5 and 10 years, respectively. Negative predictors of long-term survival included advanced age(HR, 1.1;P < .001), history of myocardial infarction (HR, 1.37;P =.02), and renal insufficiency (HR, 1.5; P =.04). Freedom from graft-related reintervention was 98.2% +/- 0.8% and 94.3% +/- 3.4% at 5 and 10 years, respectively. There were 13 late graft-related complications in 11 (2%) patients (mean follow-up, 7.2 years). Findings included seven anastomotic pseudoaneurysms (five were repaired), four graft limb occlusions, and two graft infections. Aneurysms were identified in noncontiguous arterial segments in 68 (45%) of 152 patients, most of which involved the iliac arteries and required no treatment because of small size. Late aortic aneurysms proximal to the repair were identified in 24% of patients, and 29 (19%) patients had multiple late synchronous aneurysms. Conclusions. Open repair remains a safe and durable option for the management of abdominal aortic aneurysms, with an excellent associated 10-year survival in patients who undergo operation at 75 years of age or younger. In addition, the freedom from graft-related reintervention is superior to that of EVAR. Finally, continued surveillance after open repair is appropriate and should be directed toward the detection of other aneurysms. C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Gen Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Conrad, MF (reprint author), WAC 4,15 Parkman St, Boston, MA 02114 USA. EM mconrad@partners.org NR 28 TC 58 Z9 63 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2007 VL 46 IS 4 BP 669 EP 675 DI 10.1016/j.jvs.2007.05.046 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 216JY UT WOS:000249875500008 PM 17903647 ER PT J AU Brothers, TE Robison, JG Elliott, BM AF Brothers, Thomas E. Robison, Jacob G. Elliott, Bruce M. TI Prospective decision analysis for peripheral vascular disease predicts future quality of life SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Southern-Association-for-Vascular-Surgery CY JAN 17-20, 2007 CL Rio Grande, PR SP So Assoc Vasc Surg ID CRITICAL LIMB ISCHEMIA; INFRAINGUINAL BYPASS; REVASCULARIZATION; SURGERY; SALVAGE; PREFERENCES; UTILITY AB Objective: Decision making for peripheral vascular disease can be quite complex as a result of pre-existing compromise of patient functional status, anatomic considerations, uncertainty of favorable outcome, medical comorbidities, and limitations in life expectancy. The ability of prospective decision-analysis models to predict individual quality of life in patients with lower extremity arterial occlusive disease was tested. Methods. This was a prospective cohort study. The settings were university and Veterans Administration vascular surgery practices. All 214 patients referred with symptomatic lower extremity arterial disease of any severity over a 2-year period were screened, and 206 were enrolled. A Markov model was compared with standard clinical decision-making. Utility assessment and generalized (Short Form-36; SF-36) and disease-specific (Walking Impairment Questionnaire; WIQ) quality of life were derived before treatment. Estimates of treatment outcome probabilities and intended and actual treatment plans were provided by attending vascular surgeons. The main outcome measures were generalized (SF-36) and disease-specific (WIQ) variables at study entry and at 4 and 12 months. Results. Primary intervention consisted of amputation for 9, bypass for 42, angioplasty for 8, and medical treatment for 147 patients. Considering all patients, no improvement in mean overall patient quality of life measured by the SF-36 Physical Component Score (27 +/- 8 vs 28 +/- 8; P =.87) or WIQ (39 +/- 22 vs 39 +/- 23; P =.13) was noted 12 months after counseling and treatment by the vascular surgeons. Individually considered SF-36 categories were improved only for Bodily Pain (40 +/- 23 vs 49 +/- 25; P =.03), with the most significant improvement observed among patients with the most severe pain (68 +/- 25 vs 37 +/- 23; P =.02) and among those undergoing bypass (60 +/- 29 vs 31 +/- 22; P =.02). It is noteworthy that when the treatment chosen was incongruent with the Markov model, patients were more likely to report a poorer quality of life at I year (Physical Component Score, 25 +/- 8 vs 29 +/- 8; P < .001). The quality of life predicted at baseline by the Markov model correlated positively with the Physical Component Score (r = 0.23), Bodily Pain (r =0.33), and Fatigue (r = 0.44) and negatively with WIQ (r = -0.08) observed 1 year later. Conclusions. Prospective application of an individualized decision Markov model in patients with vascular disease was predictive of patient quality of life at 1 year. The patient's outcome was worse when the treatment received did not follow the model's recommendation. This decision analysis model may be useful to identify patients at risk for poor outcomes with standard clinical decision making. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Brothers, TE (reprint author), 96 Jonathan Lucas,Ste 424, Charleston, SC 29425 USA. EM brothete@musc.edu NR 39 TC 16 Z9 17 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 2007 VL 46 IS 4 BP 701 EP 708 DI 10.1016/j.jvs.2007.05.045 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 216JY UT WOS:000249875500013 PM 17765449 ER PT J AU Patel, VI Hamdan, AD Schermerhorn, ML Hile, C Dahlberg, S Campbell, DR LoGerfo, FW Pomposelli, FB AF Patel, Virendra I. Hamdan, Allen D. Schermerhorn, Marc L. Hile, Chantel Dahlberg, Suzanne Campbell, David R. LoGerfo, Frank W. Pomposelli, Frank B. TI Lower extremity arterial revascularization in obese patients SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 17, 2005 CL Stowe, VT SP New England Soc Vasc Surg ID BODY-MASS INDEX; US ADULTS; BYPASS; PREVALENCE; MORTALITY; OUTCOMES; SURGERY; RISK AB Background: Obesity and associated comorbidities are associated with a high rate of complications and technical difficulties after a number of surgical procedures. We studied the role of obesity in outcomes in lower extremity arterial revascularization. Methods: We reviewed all lower extremity arterial revascularizations performed at our institution in 2000. Body mass index (BMI) greater than or equal to 30 kg/m(2) defined obesity. Perioperative outcomes, long-term survival, and graft patency were evaluated in obese and nonobese patients by using linear regression, the Fisher exact test, and Kaplan-Meier analysis. Results: The study population consisted of 74 (26%) obese and 207 (74%) nonobese patients. Patient demographics of the obese and nonobese populations were similar. The mean BMI for obese patients was 35 +/- 5 kg/m(2) and in nonobese patients was 25 +/- 3 kg/m(2). The mean age of each group was 67 +/- 10 years (BMI >= 30 kg/m(2)) and 70 +/- 13 years (BMI < 30 k g/m(2)). There were 45 (61%) obese men and 29 (39%) obese women. There were 128 (62%) nonobese men and 79 (38%) nonobese women. Diabetes was present in 76% of the obese and 70% of the nonobese patients. Perioperative myocardial infarction, 30-day mortality, and rate of reoperation within 30 days were not significantly different. Obese patients had higher increased postoperative wound infection rates (16% vs 7%; P =.04). Survival analysis showed 81% 5% and 85% +/- 3% 1 -year survival and 66% +/- 6% and 62% +/- 3% 3-year survival in obese and nonobese patients (P=.58), respectively. Kaplan-Meier estimates showed no effect of obesity on long-term graft patency, with 1-year graft patency rates of 82% +/- 6% and 81% +/- 4% in obese and nonobese patients, respectively (P =.79). Conclusions. Obese patients have similar limb salvage rates, perioperative cardiac morbidity, long-term survival rates, and long-term graft patency but have increased perioperative wound infections. C1 Beth Israel Deaconess Med Ctr, Dept Vasc & Endovasc Surg, Boston, MA 02215 USA. RP Patel, VI (reprint author), Massachusetts Gen Hosp, Dept Vasc & Endovasc Surg, 15 Parkman St,WAC 458, Boston, MA 02114 USA. EM vpatel4@partners.org FU NHLBI NIH HHS [T32 HL007734] NR 11 TC 21 Z9 21 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2007 VL 46 IS 4 BP 738 EP 742 DI 10.1016/j.jvs.2007.05.044 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 216JY UT WOS:000249875500020 PM 17764878 ER PT J AU Butt, AA Skanderson, M McGinnis, KA Ahuja, T Bryce, CL Barnato, AE Chang, CCH AF Butt, A. A. Skanderson, M. McGinnis, K. A. Ahuja, T. Bryce, C. L. Barnato, A. E. Chang, C.-C. H. TI Impact of hepatitis C virus infection and other comorbidities on survival in patients on dialysis SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE CKD; dialysis; HCV; HIV; survival; USRDS ID ALPHA-2A PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2A; HEMODIALYSIS-PATIENTS; MOLECULAR EVIDENCE; NOSOCOMIAL TRANSMISSION; UNITED-STATES; HIV; MORTALITY; VETERANS; COINFECTION AB The impact of hepatitis C virus (HCV) and other comorbid conditions upon survival is not well quantified in patients on dialysis. We identified HCV-infected and uninfected persons in the USRDS using claims data in 1997-1998 and followed until September 22, 2002 or death. We used Gray's time-varying coefficients model to examine factors associated with survival. Subjects with a renal transplant were excluded. A total of 5737 HCV-infected and 11 228 HCV-uninfected persons were identified. HCV-infected subjects were younger (mean age 57.8 vs 65.3 years), more likely to be male (57.6%vs 49.6%) and black (54.0%vs 36.4%). They were more likely to have a diagnosis of drug (16.5%vs 4.6%) and alcohol use (14.0%vs 3.1%), and to be human immunodeficiency virus (HIV) co-infected (7.4%vs 1.8%) (all comparisons, P < 0.0005). In an adjusted Gray's time-varying coefficient model, HCV was associated with an increased risk of mortality (P < 0.0005). The hazards were highest at the time of HCV diagnosis and decreased to a stable level 2 years after diagnosis. Other factors associated with increased risk of mortality were (P < 0.0005 unless stated) HIV coinfection; diagnosis of drug use (P = 0.001); coronary artery disease (P = 0.006); stroke; diabetes as the primary cause for renal failure; peripheral vascular disease; depression and presence of anaemia. HCV was associated with higher risk of death in patients on dialysis, even after adjusting for concurrent comorbidities. The risk was highest at the time of HCV diagnosis and stabilized over time. Clinical trials of HCV screening and treatment to reduce mortality in this population are warranted. C1 Univ Pittsburgh, Med Ctr, Div Infect Dis, Pittsburgh, PA USA. Va Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Unin Ctr Social & Urban Res, Pittsburgh, PA USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Butt, AA (reprint author), Univ Pittsburgh, Med Ctr, 3601 Fifth Ave,Suite 3A,Falk Bldg, Pittsburgh, PA 15213 USA. EM butta@dom.pitt.edu OI Bryce, Cindy/0000-0001-6356-6675 FU NCATS NIH HHS [UL1 TR000005]; NIDA NIH HHS [DA016175-01A1] NR 34 TC 27 Z9 30 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD OCT PY 2007 VL 14 IS 10 BP 688 EP 696 DI 10.1111/j.1365-2893.2007.00853.x PG 9 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 210ZB UT WOS:000249493000002 PM 17875003 ER PT J AU Diaz-Griffero, F Kar, A Perron, M Xiang, SH Javanbakht, H Li, X Sodroski, J AF Diaz-Griffero, Felipe Kar, Alak Perron, Michel Xiang, Shi-Hua Javanbakht, Hassan Li, Xing Sodroski, Joseph TI Modulation of retroviral restriction and proteasorne inhibitor-resistant turnover by changes in the TRIM5 alpha B-Box 2 domain SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; CYTOPLASMIC BODIES; B30.2(SPRY) DOMAIN; MONKEY TRIM5-ALPHA; CAPSID-BINDING; TRIM11 BINDS; OLD-WORLD; PROTEIN; HIV-1 AB An intact B-box 2 domain is essential for the antiretroviral activity of TRIM5 alpha. We modeled the structure of the B-box 2 domain of TRIM5 alpha based on the existing three-dimensional structure of the B-box 2 domain of human TRIM29. Using this model, we altered the residues predicted to be exposed on the surface of this globular structure. Most of the alanine substitutions in these residues exerted little effect on the antiretroviral activity of human TRIM5c alpha(hu). or rhesus monkey TRIM5C alpha(rh). However, alteration of arginine 119 of TRIM5 alpha(hu). or the corresponding arginine 121 of TRIM5 alpha(rh), diminished the abilities of the proteins to restrict retroviral infection without affecting trimerization or recognition of the viral capsid. The abilities of these functionally defective TRIM5 alpha proteins to accelerate the uncoating of the targeted retroviral capsid were abolished. Removal of the positively charged side chain from B-box 2 arginines 119/120/121 resulted in diminished proteasome-independent turnover of TRIM5 alpha and the related restriction factor TRIMCyp. However, testing of an array of mutants revealed that the rapid turnover and retroviral restriction functions of this B-box 2 region are separable. C1 Harvard Univ, Sch Med, Dept Pathol,Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dept Pathol,Dept Canc Immunol & AIDS, Dana Farber Canc Inst, 44 Binney St-JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009 FU NIAID NIH HHS [R01 AI063987, AI60354, AI063987, P30 AI060354] NR 42 TC 53 Z9 57 U1 0 U2 8 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 2007 VL 81 IS 19 BP 10362 EP 10378 DI 10.1128/JVI.00703-07 PG 17 WC Virology SC Virology GA 212SP UT WOS:000249617400017 PM 17626085 ER PT J AU Lima, MA Marzocchetti, A Autissier, P Tompkins, T Chen, YP Gordon, J Clifford, DB Gandhi, RT Venna, N Berger, JR Koralnik, IJ AF Lima, Marco A. Marzocchetti, Angela Autissier, Patrick Tompkins, Troy Chen, Yiping Gordon, Jennifer Clifford, David B. Gandhi, Rajesh T. Venna, Nagagopal Berger, Joseph R. Koralnik, Igor J. TI Frequency and phenotype of JC virus-specific CD8(+) T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy (vol 81, pg 3361, 2007) SO JOURNAL OF VIROLOGY LA English DT Correction C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02215 USA. Univ Fed Rio de Janeiro, Sch Med, Rio De Janeiro, Brazil. Temple Univ, Ctr Neurovirol & Canc Biol, Philadelphia, PA 19122 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY USA. RP Lima, MA (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 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 2007 VL 81 IS 19 BP 10835 EP 10835 DI 10.1128/JVI.01621-07 PG 1 WC Virology SC Virology GA 212SP UT WOS:000249617400064 ER PT J AU Norian, LA Rodriguez, P O'Mara, L Zabaleta, J Ochoa, A Allen, PM AF Norian, Lyse A. Rodriguez, Paulo O'Mara, Leigh Zabaleta, Jovanny Ochoa, Augusto Allen, Paul M. TI Tumors induce regulatory dendritic cells that suppress CD8+T cell antitumor immunity SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA 02138 USA. Univ Nacl Colombia, Int Ctr Phys, Bogota, Colombia. 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 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2007 VL 16 IS 8 BP 1099 EP 1099 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 225GW UT WOS:000250506100013 ER PT J AU Torres-Arzayus, MI Zhao, J Bronson, R Brown, M AF Torres-Arzayus, Maria I. Zhao, Jin Bronson, Roderick Brown, Myles TI Estrogen-dependent and independent-mechanisms contribute to AIB1-Mediated tumor formation SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA 02138 USA. Univ Nacl Colombia, Int Ctr Phys, Bogota, Colombia. 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 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2007 VL 16 IS 8 BP 1099 EP 1100 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 225GW UT WOS:000250506100014 ER PT J AU Kilpatrick, LA Ornitz, E Ibrahimovic, H Craske, M Nazarian, M Mayer, EA Naliboff, BD AF Kilpatrick, Lisa A. Ornitz, Edward Ibrahimovic, Hana Craske, Michelle Nazarian, Maria Mayer, Emeran A. Naliboff, Bruce D. TI Sex-related differences in irritable bowel syndrome (IBS) prepulse startle modification SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 Univ CA, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90095 USA. Univ CA, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ CA, David Geffen Sch Med, Dept Psychol, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 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 2007 VL 16 IS 8 BP 1110 EP 1110 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 225GW UT WOS:000250506100041 ER PT J AU Frayne, SM Yu, W Yano, EM Ananth, L Iqbal, S Thrailkill, A Phibbs, CS AF Frayne, Susan M. Yu, Wei Yano, Elizabeth M. Ananth, Lakshmi Iqbal, Samina Thrailkill, Ann Phibbs, Ciaran S. TI Gender and use of care: Planning for tomorrow's veterans health administration SO JOURNAL OF WOMENS HEALTH LA English DT Article ID AFFAIRS MEDICAL-CENTER; WOMEN VETERANS; MENTAL-HEALTH; FEMALE VETERANS; AVERAGE COST; VA; SERVICES; HOSPITALS; MILITARY; SATISFACTION AB Historically, men have been the predominant users of Veterans Health Administration (VHA) care. With more women entering the system, a systematic assessment of their healthcare use and costs of care is needed. We examined how utilization and costs of VHA care differ in women veterans compared with men veterans. Methods: In this cross-sectional study using centralized VHA administrative databases, main analyses examined annual outpatient and inpatient utilization and costs of care (outpatient, inpatient, and pharmacy) for all female (n = 178,849) and male (n = 3,943,532) veterans using VHA in 2002, accounting for age and medical/mental health conditions. Results: Women had 11.8% more outpatient encounters, 25.9% fewer inpatient days, and 11.4% lower total cost than men; after adjusting for age and medical comorbidity, differences were less pronounced (1.3%, 10.9%, and 2.8%, respectively). Among the 30.8% of women and 24.4% of men with both medical and mental health conditions, women used outpatient services more heavily than men (31.0 vs. 27.3 annual encounters). Conclusions: VHA's efforts to build capacity for women veterans must account for their relatively high utilization of outpatient services, which is especially prominent in women who have both medical and mental health conditions. Meeting their needs may require delivery systems integrating medical and mental healthcare. C1 VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. Stanford Univ, Sch Med, Div Gen Internal Med, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Ctr Hlth Policy, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Palo Alto, CA 94304 USA. VA Palo Alto Hlth Care Syst, Womens Hlth Ctr, Palo Alto, CA USA. VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA 94025 USA. VA Greator Los Angeles HSR&D Ctr Study Heathcare, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. RP Frayne, SM (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Williow Rd,152-MPD, Menlo Pk, CA 94025 USA. EM sfrayne@stanford.edu NR 47 TC 32 Z9 32 U1 3 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2007 VL 16 IS 8 BP 1188 EP 1199 DI 10.1089/jwh.2006.0205 PG 12 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 225GW UT WOS:000250506100063 PM 17937572 ER PT J AU McCarter, R Mejia, W Ikeno, Y Monnier, V Kewitt, K Gibbs, M McMahan, A Strong, R AF McCarter, Roger Mejia, Walter Ikeno, Yuji Monnier, Vincent Kewitt, Kristen Gibbs, Michael McMahan, Alex Strong, Randy TI Plasma glucose and the action of calorie restriction on aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID TRANSGENIC MICE; FISCHER-344 RATS; TRANSPORTER GENE; HUMAN GLUT4; LONGEVITY; AGE; EXPRESSION; MECHANISM; LESIONS AB We tested the hypothesis that retardation of aging by caloric restriction is due in part to decreased levels of plasma glucose over the life span. Male C57BL/6 mice expressing a human GLUT4 minigene (transgenic [TG] mice) and their nontransgenic littermates (NTG mice) were maintained under specific pathogen-free conditions. Mice were fed ad libitum (A mice) or 40% less than ad libitum (R mice) from age 6 weeks. Over the life span there were three different levels of plasma glucose, with NTGA mice having the highest daily levels, TGR mice the lowest daily values, and TGA and NTGR mice having similar levels intermediate between these values. Despite differences in plasma glucose, the differences measured in longevity (50% and 10% survival), physiology and tissue pathology were associated with diet rather than with levels of plasma glucose. We conclude that decreased plasma glucose over the life span is not an important factor in the action of calorie restriction on aging processes. C1 [McCarter, Roger; Mejia, Walter; Kewitt, Kristen] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [McMahan, Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Ikeno, Yuji; Strong, Randy] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Res Serv, San Antonio, TX USA. [Gibbs, Michael] Pfizer Res Labs, Groton, CT USA. [Monnier, Vincent] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. RP McCarter, R (reprint author), Penn State Univ, Ctr Dev & Hlth Genet, Gardner House, University Pk, PA 16802 USA. EM rjm28@psu.edu FU NIA NIH HHS [P01 AG-14674] NR 37 TC 26 Z9 26 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 2007 VL 62 IS 10 BP 1059 EP 1070 PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 272AF UT WOS:000253829100001 PM 17921417 ER PT J AU Johnson, JK Lui, LY Yaffe, K AF Johnson, Julene K. Lui, Li-Yung Yaffe, Kristine TI Executive function, more than global cognition, predicts functional decline and mortality in elderly women SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LUIS VALLEY HEALTH; OLDER PERSONS; INSTRUMENTAL ACTIVITIES; ALZHEIMER-DISEASE; NEUROPSYCHOLOGICAL TESTS; DYSEXECUTIVE SYMPTOMS; PREFRONTAL GRAY; RISK-FACTORS; IMPAIRMENT; DISABILITY AB Background. Functional impairment in community-dwelling older adults is common and is associated with poor outcomes. Our goal was to compare the contribution of impairment in executive function or global cognitive function to predicting functional decline and mortality. Methods. We studied 7717 elderly women enrolled in a prospective study (mean age 73.3 years) and identified women with poor baseline executive function (score > 1 standard deviation [SD] below the mean on the Trail Making Test B (Trails B; n = 957, 12.4%), poor global cognitive function (score > 1 SD below the mean on a modified Mini-Mental State Examination [mMMSE], n = 387, 5.0%), impairment in both (n = 249, 3.2%), or no impairment (n = 6124, 79.4%). We compared level of functional difficulty (Activities of Daily Living [ADLs] and Instrumental ADLs [IADLs]) at baseline and at 6-year follow-up and survival at follow-up. We also determined if the association was independent of age, education, depression, medical comorbidities, and baseline functional ability. Results. At baseline, women with Trails B impairment only or impairment on both tests reported the highest proportion of ADL and IADL dependence compared to the other groups. At the 6-year follow-up after adjusting for age, education, medical comorbidities, depression, and baseline ADL or IADL, women with only Trails B impairment were 1.3 times more likely to develop an incident ADL dependence (adjusted odds ratio [OR] = 1.34; 95% confidence interval [CI], 1.07-1.69) and 1.5 times more likely to develop a worsening of ADL dependence (adjusted OR = 1.48; 95% CI, 1.16-1.89) when compared to women with no impairment on either test. In addition, women with only Trails B impairment had a 1.5-fold increased risk of mortality (adjusted hazard ratio [HR] = 1.48; 95% CI, 1.21-1.81). In contrast, women with impairment on only mMMSE were not at increased risk to develop incident ADL or IADL dependence, a worsening of ADL or IADL dependence, or mortality. Conclusion. Compared to women with no impairment, women with executive function impairment had significantly worse ADL and IADL function cross-sectionally and over 6 years. Individuals with executive dysfunction also had increased risk of mortality. These results suggest that screening of executive function can help to identify women who are at risk for functional decline and decreased survival. C1 [Johnson, Julene K.; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94117 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Med, San Francisco, CA 94117 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94117 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Lui, Li-Yung] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. RP Johnson, JK (reprint author), Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, 350 Parnassus,Suite 706, San Francisco, CA 94117 USA. EM jjohnson@memory.ucsf.edu FU NIA NIH HHS [L30 AG024692, AG05394, AG05407, R01 AG005394, R01 AG005407, R01 AG021918, R01 AG021918-01, R01 AG022538, R01 AG022538-04, R01 AG026720, R01 AG026720-01, R01-AG22538]; NIAMS NIH HHS [AR35582, AR35583, AR35584, R01 AR035582, R01 AR035583, R01 AR035584] NR 54 TC 110 Z9 116 U1 1 U2 11 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 2007 VL 62 IS 10 BP 1134 EP 1141 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 272AF UT WOS:000253829100011 PM 17921427 ER PT J AU Chuang, PY Yu, Q Fang, W Uribarri, J He, JC AF Chuang, P. Y. Yu, Q. Fang, W. Uribarri, J. He, J. C. TI Advanced glycation endproducts induce podocyte apoptosis by activation of the FOXO4 transcription factor SO KIDNEY INTERNATIONAL LA English DT Article DE phosphorylation; RAGE; Akt; advanced glycation endproducts; transcription factor ID GLYCOSYLATION END-PRODUCTS; DIABETIC-NEPHROPATHY; OXIDANT STRESS; OXIDATIVE STRESS; BINDING-PROTEINS; CELL-SURFACE; KINASE; EXPRESSION; RECEPTOR; GLOMERULOSCLEROSIS AB Advanced glycation endproducts ( AGEs) and a receptor for AGEs ( RAGE) have been linked in the pathogenesis of diabetic nephropathy. RAGE is usually localized to podocytes and is increased in diabetes. RAGE activation increases reactive oxygen species production, which mediates hyperglycemia-induced podocyte apoptosis in early diabetic nephropathy. Here, we examined the interaction of AGE and RAGE on podocyte apoptosis. When we exposed murine cultured podocytes to bovine serum albumin ( BSA) that was modified by AGEs or to carboxymethyl-lysine BSA, more apoptosis was found when compared with unmodified BSA. Similarly, more podocytes underwent detachment and apoptosis when cultured on AGE-modified collagen IV than on native collagen IV. AGEs isolated from sera of patients with chronic kidney disease also caused apoptosis of podocytes. Apoptosis was diminished by small interference RNA ( siRNA) for RAGE in podocytes exposed to AGE-BSA, but not to AGE-modified collagen IV. Both AGE- and carboxymethyl-lysine modified-BSA activated p38MAP kinase and inhibition of this kinase reduced the apoptotic effect of AGE-BSA. Exposure to AGE-BSA was associated with Akt dephosphorylation and FOXO4 transcriptional activation leading to an increase in the expression of an effector protein of apoptosis, Bim. siRNA for FOXO4 abolished AGE-BSA-induced apoptosis of podocytes. Our study suggests that an AGE-RAGE interaction contributes to podocyte apoptosis by activation of the FOXO4 transcription factor. C1 CUNY Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. James J Peters VA Med Ctr, New York, NY USA. RP He, JC (reprint author), CUNY Mt Sinai Sch Med, Dept Med Nephrol, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM cijiang.he@mssm.edu FU NIDDK NIH HHS [K08 DK-65495, K08 DK065495, R01 DK078897] NR 35 TC 69 Z9 78 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2007 VL 72 IS 8 BP 965 EP 976 DI 10.1038/sj.ki.5002456 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 219NB UT WOS:000250090800011 PM 17667983 ER PT J AU Wolf, M Shah, A Gutierrez, O Ankers, E Monroy, M Tamez, H Steele, D Chang, Y Camargo, CA Tonelli, M Thadhani, R AF Wolf, M. Shah, A. Gutierrez, O. Ankers, E. Monroy, M. Tamez, H. Steele, D. Chang, Y. Camargo, C. A., Jr. Tonelli, M. Thadhani, R. TI Vitamin D levels and early mortality among incident hemodialysis patients SO KIDNEY INTERNATIONAL LA English DT Article DE vitamin D; calcitriol; kidney disease ID TANDEM MASS-SPECTROMETRY; MAINTENANCE HEMODIALYSIS; HIGH PREVALENCE; D DEFICIENCY; 25-HYDROXYVITAMIN D-3-1-ALPHA-HYDROXYLASE; 1,25-DIHYDROXYVITAMIN D-3; HYPOVITAMINOSIS-D; DIALYSIS PATIENTS; D INSUFFICIENCY; D INADEQUACY AB Vitamin D deficiency is associated with cardiovascular disease, the most common cause of mortality in hemodialysis patients. To investigate the relation between blood levels of 25-hydroxyvitamin D ( 25D) and 1,25-dihydroxyvitamin D ( 1,25D) with hemodialysis outcomes, we measured baseline vitamin D levels in a cross-sectional analysis of 825 consecutive patients from within a prospective cohort of incident US hemodialysis patients. Of these patients, 78% were considered vitamin D deficient with 18% considered severely deficient. Calcium, phosphorus, and parathyroid hormone levels correlated poorly with 25D and 1,25D concentrations. To test the association between baseline vitamin D levels and 90-day mortality, we selected the next 175 consecutive participants who died within 90 days and compared them to the 750 patients who survived in a nested case-control analysis. While low vitamin D levels were associated with increased mortality, significant interaction was noted between vitamin D levels, subsequent active vitamin D therapy, and survival. Compared to patients with the highest 25D or 1,25D levels who received therapy, untreated deficient patients were at significantly increased risk for early mortality. Our study shows that among incident hemodialysis patients, vitamin D deficiency is common, correlates poorly with other components of mineral metabolism and is associated with increased early mortality. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gen Med Div, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Univ Alberta, Dept Med, Edmonton, AB, Canada. RP Thadhani, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Bulfinch 127,55 Fruit St, Boston, MA 02115 USA. EM rthadhani@partners.org RI Tonelli, Marcello/B-3028-2009 FU NIDDK NIH HHS [DK71674] NR 54 TC 483 Z9 505 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2007 VL 72 IS 8 BP 1004 EP 1013 DI 10.1038/sj.ki.5002451 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 219NB UT WOS:000250090800015 PM 17687259 ER PT J AU Rademakers, R Baker, M Gass, J Adamson, J Huey, ED Momeni, P Spina, S Coppola, G Karydas, AM Stewart, H Johnson, N Hsiung, GY Kelley, B Kuntz, K Steinbart, E Wood, EM Yu, CE Josephs, K Sorenson, E Womack, KB Weintraub, S Pickering-Brown, SM Schopeld, PR Brooks, WS van Deerlin, VM Snowden, J Clark, CM Kertesz, A Boylan, K Ghetti, B Neary, D Schellenberg, GD Beach, TG Mesulam, M Mann, D Grafman, J Mackenzie, IR Feldman, H Bird, T Petersen, R Knopman, D Boeve, B Geschwind, DH Miller, B Wszolek, Z Lippa, C Bigio, EH Dickson, D Graff-Radford, N Hutton, M AF Rademakers, Rosa Baker, Matt Gass, Jennifer Adamson, Jennifer Huey, Edward D. Momeni, Parastoo Spina, Salvatore Coppola, Giovanni Karydas, Anna M. Stewart, Heather Johnson, Nancy Hsiung, Ging-Yuek Kelley, Brendan Kuntz, Karen Steinbart, Ellen Wood, Elisabeth McCarty Yu, Chang-En Josephs, Keith Sorenson, Eric Womack, Kyle B. Weintraub, Sandra Pickering-Brown, Stuart M. Schopeld, Peter R. Brooks, William S. van Deerlin, Vivianna M. Snowden, Julie Clark, Christopher M. Kertesz, Andrew Boylan, Kevin Ghetti, Bernardino Neary, David Schellenberg, Gerard D. Beach, Thomas G. Mesulam, Marsel Mann, David Grafman, Jordan Mackenzie, Ian R. Feldman, Howard Bird, Thomas Petersen, Ron Knopman, David Boeve, Bradley Geschwind, Dan H. Miller, Bruce Wszolek, Zbigniew Lippa, Carol Bigio, Eileen H. Dickson, Dennis Graff-Radford, Neill Hutton, Mike TI Phenotypic variability associated with progranulin haploinsufficiency in patients with the common 1477C -> T (Arg493X) mutation: an international initiative SO LANCET NEUROLOGY LA English DT Article ID FRONTOTEMPORAL LOBAR DEGENERATION; NULL MUTATIONS; GENE-MUTATIONS; DEMENTIA; TAU; CHROMOSOME-17; INCLUSIONS; DISEASE; NEUROPATHOLOGY; PATHOLOGY AB Background The progranulin gene (GRN) is mutated in 5-10% of patients with frontotemporal lobar degeneration (FTLD) and in about 20% of patients with familial FTLD. The most common mutation in GRN is Arg493X. We aimed to establish the contribution of this mutation to FTLD and related disorders. Methods We measured the frequency of Arg493X in 3405 unrelated patients with various neurodegenerative diseases using Taqman single-nucleotide polymorphism (SNP) genotyping. Clinicopathological characterisation and shared haplotype analysis were done for 30 families with FTLD who carry Arg493X. To investigate the effect of potential modifying loci, we did linear regression analyses with onset age as the covariate for GRN variants, for genotypes of the apolipoprotein E gene (APOE), and for haplotypes of the microtubule-associated protein tau gene (MAPT). Findings Of 731 patients with FTLD, 16 (2%) carried Arg493X. This mutation was not detected in 2674 patients who did not have FTLD. In 37 patients with Arg493X from 30 families with FTLD, clinical diagnoses included frontotemporal dementia, primary progressive aphasia, corticobasal syndrome, and Alzheimer's disease. Range of onset age was 44-69 years. In all patients who came to autopsy (n=13), the pathological diagnosis was FTLD with neuronal inclusions that contained TAR DNA-binding protein or ubiquitin, but not tau. Neurofibrillary tangle pathology in the form of Braak staging correlated with overall neuropathology in the Arg493X carriers. Haplotype analyses suggested that Arg493X arose twice, with a single founder for 27 families. Linear regression analyses suggested that patients with SNP rs9897528 on their wild-type GRN allele have delayed symptom onset. Onset ages were not associated with the MAPT H1 or H2 haplotypes or APOE genotypes, but early memory deficits were associated with the presence of an APOE epsilon 4 allele. Interpretation Clinical heterogeneity is associated with GRN haploinsufficiency, and genetic variability on the wild-type GRN allele might have a role in the age-related disease penetrance of GRN mutations. C1 Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. NINDS, NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Neurol, Lubbock, TX 79409 USA. Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA. Univ Siena, I-53100 Siena, Italy. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Vancouver Gen Hosp, ALS Ctr, Vancouver, BC, Canada. Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimer Dis Ctr, Chicago, IL USA. Univ British Columbia, Div Neurol, Vancouver, BC V5Z 1M9, Canada. Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Washington, Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Med Neurol, Seattle, WA USA. Univ Washington, Dept Pharmacol, Seattle, WA USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX USA. Univ Manchester, Fac Med & Hlth Sci, Manchester, Lancs, England. Prince Wales Med Res Inst, Sydney, NSW, Australia. Univ Penn, Sch Med, Rush Alzheimers Dis Ctr, Dept Neurol, Philadelphia, PA 19104 USA. Univ Western Ontario, London, ON, Canada. Mayo Clin, Coll Med, Dept Neurol, Jacksonville, FL 32224 USA. Sun Hlth Res Inst, Sun City, AZ USA. Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada. Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Rademakers, R (reprint author), Mayo Clin, Coll Med, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM rademakers.rosa@mayo.edu RI Pickering-Brown, Stuart/D-4008-2009; OI Pickering-Brown, Stuart/0000-0003-1561-6054; Grafman, Jordan H./0000-0001-8645-4457; Dickson, Dennis W/0000-0001-7189-7917; Snowden, Julie/0000-0002-3976-4310; Womack, Kyle/0000-0002-6060-9075; Feldman, Howard/0000-0002-9258-4538 FU Intramural NIH HHS; Medical Research Council [G0400356]; NIA NIH HHS [P50 AG03006, P01 AG017216, P01 AG019724, P01 AG17586, P30 AG10133, P30 AG12300, P30 AG13854, P30 AG19610, P50 AG05136, P50 AG16574, R01 AG026251, R01 AG026938]; NINDS NIH HHS [P50 NS40256] NR 37 TC 126 Z9 128 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD OCT PY 2007 VL 6 IS 10 BP 857 EP 868 DI 10.1016/S14744422(07)70221-1 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 218SQ UT WOS:000250035600016 PM 17826340 ER PT J AU Khor, LY Bae, K Pollack, A Hammond, MEH Grignon, DJ Venkatesan, VM Rosenthal, SA Ritter, MA Sandler, HM Hanks, GE Shipley, WU Dicker, AP AF Khor, Li-Yan Bae, Kyounghwa Pollack, Alan Hammond, M. Elizabeth H. Grignon, David J. Venkatesan, Varagur M. Rosenthal, Seth A. Ritter, Mark A. Sandler, Howard M. Hanks, Gerald E. Shipley, William U. Dicker, Adam P. TI COX-2 expression predicts prostate-cancer outcome: analysis of data from the RTOG 92-02 trial SO LANCET ONCOLOGY LA English DT Article ID SELECTIVE CYCLOOXYGENASE-2 INHIBITOR; RADIATION-THERAPY; RADICAL PROSTATECTOMY; ANDROGEN DEPRIVATION; CARCINOMA-CELLS; NEOADJUVANT RADIOCHEMOTHERAPY; METASTATIC DISSEMINATION; OVER-EXPRESSION; LOCAL-CONTROL; RADIOTHERAPY AB Background COX-2 is overexpressed in some cancers, including prostate cancer; however, little is known about the effect of COX-2 overexpression on outcome in radiation-treated patients with prostate cancer. We aimed to study COX-2 overexpression and outcome in a well-defined cohort of men who received treatment with short-term androgen deprivation (STAD) plus radiotherapy or long-term androgen deprivation (LTAD) plus radiotherapy. Methods Men with prostate cancer who had participated in the Radiation Therapy Oncology Group (RTOG) 92-02 trial and for whom sufficient diagnostic tissue was available for immumohistochemical staining and image analysis of COX-2 expression were enrolled in this study. Patients in the 92-02 trial had been randomly assigned to treatment with STAD plus radiotherapy or LTAD plus radiotherapy. Multivariate analyses by Cox proportional hazards models were done to assess whether associations existed between COX-2 staining intensity and the RTOG 92-02 primary endpoints of biochemical failure (assessed by the American Society for Therapeutic Radiology and Oncology [ASTRO] and Phoenix criteria), local failure, distant metastasis, cause-specific mortality overall mortality, and any failure. Findings 586 patients with sufficient diagnostic tissue for immumohistochemical staining and image analysis of COX-2 expression were included in this study. In the multivariate analyses, the intensity of COX-2 staining as a continuous covariate was an independent predictor of distant metastasis (hazard ratio [HR] 1.181 [95% CI 1.077-1.295], p=0.0004); biochemical failure by two definitions (ASTRO, HR 1.073 [1.018-1.131], p=0.008; Phoenix HR 1.073 [1.014-1.134], p=0.014); and any failure (HR 1.068 [1.015-1.124], p=0.011). The higher the expression of COX-2, the greater the chance of failure. As a dichotomous covariate, COX-2 overexpression seemed to be most discriminating of outcome for those who received STAD compared with those who received LTAD. Interpretation To our knowledge, this is the first study to establish an association of COX-2 expression with outcome in patients with prostate cancer who have had radiotherapy. Increasing COX-2 expression was significantly associated with biochemical failure, distant metastasis, and any failure. COX-2 inhibitors might improve patient response to radiotherapy in those treated with or without androgen deprivation. Our findings suggest that LTAD might overcome the effects of COX-2 overexpression. Therefore, COX-2 expression might be useful in selecting patients who need LTAD. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Amer Coll Radiol, Radiat Therapy Oncol Grp, Philadelphia, PA USA. LDS Hosp, Intermt Hlth Care, Salt Lake City, UT USA. Indiana Univ, Indianapolis, IN 46204 USA. Univ Western Ontario, London, ON, Canada. Sacramento Med Grp, Sacramento, CA USA. Univ Wisconsin, Madison, WI USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Thomas Jefferson Univ, Dept Radiat Oncol, Philadelphia, PA 19107 USA. RP Dicker, AP (reprint author), Thomas Jefferson Univ, Dept Radiat Oncol, Philadelphia, PA 19107 USA. EM adam.dicker@mail.tju.edu OI Dicker, Adam/0000-0003-0733-3337 FU NCI NIH HHS [U10 CA032115, CA-006927, CA-101984-01, CA-109556, CA-21661, CA-32115, P30 CA006927, R01 CA101984, R01 CA106633, R01 CA106633-01, R01 CA106633-02, R01 CA106633-03, R01 CA106633-04, R01 CA109556, U10 CA021661] NR 49 TC 64 Z9 66 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2007 VL 8 IS 10 BP 912 EP 920 DI 10.1016/S1470-2045(07)70280-2 PG 9 WC Oncology SC Oncology GA 221TA UT WOS:000250249000029 PM 17881290 ER PT J AU BuSaba, NY Schaumberg, DA AF BuSaba, Nicolas Y. Schaumberg, Debra A. TI Predictors of prolonged length of stay after major elective head and neck surgery SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 110th Annual Meeting of the Triological-Society CY APR 26-29, 2007 CL San Diego, CA SP Triol Soc DE length of stay; operative complications; head and neck surgery; preoperative patient characteristics; sociodemographics; intraoperative processes; health care outcomes ID QUALITY IMPROVEMENT PROGRAM; AORTIC-ANEURYSM REPAIR; CANCER STATISTICS; HOSPITAL COSTS; RISK-FACTORS; OUTCOMES; HEALTH; CARE; COMPLICATIONS; DETERMINANTS AB Objective/Hypothesis: Longer length of stay (LOS) after elective surgery is associated with an increased use of health care resources and higher costs. The objectives of this study were to determine the perioperative factors that predict a prolonged LOS after elective major head and neck operations and to test the hypothesis that factors related to process of care (intra- and postoperative) independently predict prolonged LOS after adjustment for preoperative patient characteristics. Study Design: Prospective hospital-based cohort study. Methods: The National VA Surgical Quality Improvement Program data were accessed for seven head and neck operations: radical neck dissection (RND) (n = 398), modified RND (n = 891), total laryngectomy (n = 431), total laryngectomy with RND (n = 747), hemiglossectomy with unilateral RND (n = 201), composite resection (n = 105), and composite resection with RND (n 312). Prolonged LOS was defined as exceeding the 75th percentile for the LOS distribution of each operation. Multivariable logistic regression analysis was performed to identify factors that predicted prolonged LOS. Results: Sixty-eight variables were analyzed among 3,050 patients who qualified for inclusion. Preoperative patient characteristics that predicted prolonged LOS were older age, poorer functional status, consumption of more than two drinks of alcohol per day, history of chronic obstructive pulmonary disease, and diabetes mellitus. Intraoperative processes that predicted prolonged LOS were a longer operative time and transfusion of erythrocytes. The postoperative variables that predicted a prolonged LOS were a return to the operating room within 30 days of the index operation and the occurrence of two or more operative complications. Conclusion: Several intraoperative processes and postoperative adverse events contributed additional predictive information for prolonged LOS, after consideration of preoperative patient characteristics. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. VA Boston HlthCare Syst, Div Otolaryngol, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP BuSaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. EM Nicolas_busaba@meei.harvard.edu NR 31 TC 27 Z9 27 U1 1 U2 2 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 2007 VL 117 IS 10 BP 1756 EP 1763 DI 10.1097/MLG.0b013e3180de4d85 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 216GP UT WOS:000249866800010 PM 17690609 ER PT J AU Al-Arashi, MY Salomatina, E Yaroslavsky, AN AF Al-Arashi, Munir Y. Salomatina, Elena Yaroslavsky, Anna N. TI Multimodal confocal microscopy for diagnosing nonmelanoma skin cancers SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE contrast agents; fluorescence; optical pathology; polarization; reflectance ID MOHS MICROGRAPHIC SURGERY; BASAL-CELL CARCINOMA; METHYLENE-BLUE; REFLECTANCE MICROSCOPY; REAL-TIME; LOCALIZATION; EXCISIONS; CONTRAST; TUMORS; GUIDE AB Background and Significance: The standard diagnostic procedure for skin cancers is invasive biopsy followed by histopathological evaluation. The biopsy may result in scarring and infection. A reliable way to noninvasively image suspicious lesions with high resolution and contrast would be valuable. In this study, the suitability of dye-enhanced multimodal confocal microscopy for the detection of nonmelanoma skin cancers was evaluated. Materials and Methods: For the experiments we used fresh tumor material stained using 0.2 mg/ml or 0.05 mg/ml aqueous solutions of methylene blue (MB) or toluidine blue TB), respectively. Reflectance, fluorescence, and fluorescence polarization images of skin specimens stained with MB and TB were excited by 656 nm and 633 nm light, respectively. Fluorescence emission and anisotropy were registered between 690 nm and 710 nm. In addition, reference reflectance images at 830 nm were acquired. In total we imaged, analyzed, and compared to histology at least 10 samples of each tumor-type including nodular basal cell carcinoma (BCC), infiltrative basal cell carcinoma, and squamous cell carcinoma (SCC). Results and Conclusion: The morphological features and appearance of skin structures in the fluorescence images correlate well with corresponding histology for all investigated tumor-types. Multi-spectral reflectance images provide information on the tissue spectral responses and are complimentary to the fluorescence images. The differences detected by fluorescence polarization in cancerous and normal structures may be used for cancerous tissue discrimination. Our results indicate the feasibility of using multimodal confocal microscopy as real-time tool for detecting skin pathology. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yaroslavsky, AN (reprint author), 314B,55 Fruit St, Boston, MA 02114 USA. EM yaroslav@ihelix.mgh.harvard.edu NR 25 TC 35 Z9 35 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD OCT PY 2007 VL 39 IS 9 BP 696 EP 705 DI 10.1002/lsm.20578 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 229QD UT WOS:000250818200002 PM 17960751 ER PT J AU Demidova-Rice, TN Salomatina, EV Yaroslavsky, AN Herman, IM Hamblin, MR AF Demidova-Rice, Tatiana N. Salomatina, Elena V. Yaroslavsky, Anna N. Herman, Ira M. Hamblin, Michael R. TI Low-level light stimulates excisional wound healing in mice SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE low-level laser; biostimulation; wound healing; mouse strain differences; smooth muscle actin; myofibroblasts ID CARPAL-TUNNEL-SYNDROME; CYTOCHROME-C-OXIDASE; HELIUM-NEON LASER; CELLULAR-RESPONSES; GENE-EXPRESSION; THERAPY; SKIN; MYOFIBROBLASTS; FIBROBLASTS; RADIATION AB Background: Low levels of laser or non-coherent light, termed low-level light therapy (LLLT) have been reported to accelerate some phases of wound healing, but its clinical use remains controversial. Methods: A full thickness dorsal excisional wound in mice was treated with a single exposure to light of various wavelengths and fluences 30 minutes after wounding. Wound areas were measured until complete healing and immunofluorescence staining of tissue samples was carried out. Results: Wound healing was significantly stimulated in BALB/c and SKH1 hairless mice but not in C5713L/6 mice. Illuminated wounds started to contract while control wounds initially expanded for the first 24 hours. We found a biphasic dose-response curve for fluence of 635-nm light with a maximum positive effect at 2 J/cm(2). Eight hundred twenty nanometer was found to be the best wavelength tested compared to 635, 670, and 720 nm. We found no difference between non-coherent 635 +/- 15-nm light from a lamp and coherent 633-nm light from a He/Ne laser. LLLT increased the number of alpha-smooth muscle actin (SMA)positive cells at the wound edge. Conclusion: LLLT stimulates wound contraction in susceptible mouse strains but the mechanism remains uncertain. C1 Tufts Univ, Sch Med, Dept Physiol,Sackler Sch Grad Biomed Sci, Grad Program Cell Mol & Dev Biol, Boston, MA 02111 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Herman, IM (reprint author), Tufts Univ, Sch Med, Dept Physiol,Sackler Sch Grad Biomed Sci, Grad Program Cell Mol & Dev Biol, 136 Harrison Ave, Boston, MA 02111 USA. EM ira.herman@tufts.edu; hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NEI NIH HHS [EY 15125, R01 EY015125]; NIAID NIH HHS [AI050875, CA/AI838801, R01 AI050875, R01 AI050875-05A1] NR 44 TC 91 Z9 93 U1 2 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD OCT PY 2007 VL 39 IS 9 BP 706 EP 715 DI 10.1002/lsm.20549 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 229QD UT WOS:000250818200003 PM 17960752 ER PT J AU O'Neill, AC Winograd, JM Zeballos, JL Johnson, TS Randolph, MA Bujold, KE Kochevar, IE Redmond, RW AF O'Neill, Anne C. Winograd, Jonathan M. Zeballos, Jose L. Johnson, T. Shane Randolph, Mark A. Bujold, Kenneth E. Kochevar, Irene E. Redmond, Robert W. TI Microvascular anastomosis using a photochemical tissue bonding technique SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE tissue bonding; anastomosis; laser repair; Rose Bengal; laser welding; collagen crosslinking ID SOLID PROTEIN SOLDER; VASCULAR ANASTOMOSES; CORNEAL INCISIONS; ROSE-BENGAL; DIODE-LASER; MICROSURGICAL ANASTOMOSIS; REPAIR; KERATODESMOS; ARTERIES; SUTURES AB Background and Objectives: Photochemical tissue bonding (PTB) combines photoactive dyes with visible light to create fluid-tight seals between tissue surfaces without causing collateral thermal damage. The potential of PTB to improve outcomes over standard of care microsurgical reanastomoses of blood vessels in ex vivo and in vivo models was evaluated. Study Design: The mechanical strength and integrity of PTB and standard microsurgical suture repairs in ex vivo porcine brachial arteries (n = 10) were compared using hydrostatic testing of leak point pressure (LPP). Femoral artery repair in vivo was measured in Sprague-Dawley rats using either standard microvascular sutures (n = 20) or PTB (n = 20). Patency was evaluated at 6 hours (n = 10) and 8 weeks post-repair (n = 10) for each group. Results: PTB produced significantly higher LPPs (1,100 +/- 150 mmHg) than suture repair (350 +/- 40 mmHg, P <0.001) in an ex vivo study. In an in vivo study all femoral arteries in both suture and PTB repair groups were patent at 6 hours post-repair. At 8 weeks post-repair the patency rate was 80% for both groups. No evidence of aneurysm formation was seen in either group and bleeding was absent from the repair site in the PTB-treated vessels, in contrast to the suture repair group. Conclusion: PTB is a feasible microvascular repair technique that results in an immediate, mechanically robust bond with short- and long-term patency rates equal to those for standard suture repair. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA 02114 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Thier 224, Boston, MA 02114 USA. EM Redmond@helix.mgh.harvard.edu NR 40 TC 35 Z9 40 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD OCT PY 2007 VL 39 IS 9 BP 716 EP 722 DI 10.1002/lsm.20548 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 229QD UT WOS:000250818200004 PM 17960755 ER PT J AU Garoff-Eaton, RJ Kensinger, EA Schacter, DL AF Garoff-Eaton, Rachel J. Kensinger, Elizabeth A. Schacter, Daniel L. TI The neural correlates of conceptual and perceptual false recognition SO LEARNING & MEMORY LA English DT Article ID INFERIOR PREFRONTAL CORTEX; EPISODIC MEMORY RETRIEVAL; FUNCTIONAL MRI; COGNITIVE NEUROSCIENCE; MONITORING HYPOTHESIS; DISTINGUISH TRUE; FMRI EVIDENCE; BRAIN; REDUCTIONS; ACTIVATION AB False recognition, broadly defined as a claim to remember something that was not encountered previously, can arise for multiple reasons. For instance, a distinction can be made between conceptual false recognition (i.e., false alarms resulting from semantic or associative similarities between studied and tested items) and perceptual false recognition (i.e., false alarms resulting from physical similarities between studied and tested items). Although false recognition has been associated with frontal cortex activity, it is unclear whether this frontal activity can be modulated by the precise relationship between studied and falsely remembered items. We used event-related fMRI to examine the neural basis of conceptual compared with perceptual false recognition. Results revealed preferential activity in multiple frontal cortex regions during conceptual false recognition, which likely reflected increased semantic processing during conceptual (but not perceptual) memory errors. These results extend recent reports that different types of false recognition can rely on dissociable neural substrates, and they indicate that the frontal activity that is often observed during false compared with true recognition can be modulated by the relationship between studied and tested items. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. Massachusetts Gen Hosp East, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kensinger, EA (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM Elizabeth.kensinger.1@bc.edu; dls@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [MH060941, R01 MH060941] NR 51 TC 38 Z9 38 U1 4 U2 13 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD OCT PY 2007 VL 14 IS 10 BP 684 EP 692 DI 10.1101/lm.695707 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 216JW UT WOS:000249875300007 PM 17911372 ER PT J AU Raaijmakers, MHGP AF Raaijmakers, M. H. G. P. TI ATP-binding-cassette transporters in hematopoietic stem cells and their utility as therapeutical targets in acute and chronic myeloid leukemia SO LEUKEMIA LA English DT Review DE ATP-binding-cassette transporter; hematopoietic stem cell; leukemic stem cell; acute myeloid leukemia; chronic myeloid leukemia ID CANCER RESISTANCE PROTEIN; SOUTHWEST-ONCOLOGY-GROUP; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW-CELLS; IN-VIVO EXPANSION; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; IMATINIB MESYLATE AB ATP-binding-cassette (ABC) transporters are evolutionary extremely well-conserved transmembrane proteins that are highly expressed in hematopoietic stem cells (HSCs). The physiological function in human stem cells is believed to be protection against genetic damage caused by both environmental and naturally occurring xenobiotics. Additionally, ABC transporters have been implicated in the maintenance of quiescence and cell fate decisions of stem cells. These physiological roles suggest a potential role in the pathogenesis and biology of stem cell-derived hematological malignancies such as acute and chronic myeloid leukemia. This paper reviews the (patho) physiological role of ABC transporters in human normal and malignant HSCs and discusses its implications for their utility as therapeutical targets to eradicate leukemic stem cells in these diseases. C1 Univ Med Ctr Nijmegen St Radboud, Nijmegen Ctr Mol Life Sci, Dept Hematol, Nijmegen, Netherlands. RP Raaijmakers, MHGP (reprint author), Harvard Univ, Sch Med, Harvard Stem Cell Inst, Massachusetts Gen Hosp,Ctr Regenerat Med, 185 Cambridge St,CPZN-4265A, Boston, MA 02114 USA. EM hraaijmakers@partners.org NR 96 TC 47 Z9 52 U1 0 U2 3 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 2007 VL 21 IS 10 BP 2094 EP 2102 DI 10.1038/sj.leu.2404859 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 211XC UT WOS:000249555600003 PM 17657220 ER PT J AU Costa, DB Kobayashi, S Tenen, DG Huberman, MS AF Costa, Daniel B. Kobayashi, Susumu Tenen, Daniel G. Huberman, Mark S. TI Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers SO LUNG CANCER LA English DT Article DE epidermal growth; factor receptor; EGFR; mutation; tyrosine kinase; inhibitors; gefitinib; L858R; Exon 19 deletions; phase II trials; prospective; lung cancer; non-small cell lung cancer ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE DOMAIN; PHASE-II TRIAL; GENE-MUTATIONS; ACTIVATING MUTATIONS; ACQUIRED-RESISTANCE; PROLONGED SURVIVAL; PREDICTIVE FACTORS; CHINESE PATIENTS; SENSITIVITY AB Purpose: Epidermal growth factor receptor (EGFR) mutations have been found in the majority of gefitinib-responsive non-small cell lung cancer (NSCLC) patients from retrospective studies. We sought to compile the available phase 11 and prospective trials of this EGFR tyrosine kinase inhibitor (TKI) to better understand the efficacy and safety of selecting patients to receive gefitinib based on their genotype. Design: We searched published trials involving EGFR-mutant patients and gefitinib. Five reports were identified (published between June 2006 and April 2007) in which gefitinib was given in a prospective manner to EGFR mutation positive patients at a dose of 250mg/day. Responses were determined by RECIST and toxicities by NCI-CTC. Results: A total of 101 patients were pooled from these studies. Fifty-nine received gefitinib as their first line of therapy and 42 after having received chemotherapy. The combined rate of complete and partial response (CR + PR) in the 99 measured patients was 80.8% (80/99) and only 7.1% (7/99) had progressive disease as best response. The response rate (CR + PR) for exon 19 deletion and L858R patients were 80.3% (53/66) and 81.8% (27/33), respectively. The median progression-free survival ranged from 7.7 to 12.9 months. Overall survival had not been reached in 4/5 reports and was 15.4 months in one of them. Gefitinib administration was safe (< 50% of patients developed grades 1-2 skin rash or diarrhea) and interstitial lung disease was only reported in two patients (2%), without deaths. Conclusions: Gefitinib monotherapy leads to objective responses in most patients with EGFR mutations. Both L858R and deletion 19 mutations derived similar clinical benefits. Small molecule TKIs are the new treatment paradigm for EGFR-mutant NSCLC. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Med Sch, Beth Israel Deacones Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA. RP Costa, DB (reprint author), Harvard Med Sch, Beth Israel Deacones Med Ctr, Div Hematol & Oncol, 330 Brookline Av,Rabb 430, Boston, MA 02215 USA. EM dbcosta@bidmc.harvard.edu RI Mendez, Pedro /J-8955-2016; OI Mendez, Pedro /0000-0001-6713-7907; Costa, Daniel/0000-0002-0689-395X; Tenen, Daniel/0000-0002-6423-3888 FU NCI NIH HHS [CA090578, P20 CA090578, P20 CA090578-01A10002, P50 CA090578] NR 62 TC 102 Z9 110 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2007 VL 58 IS 1 BP 95 EP 103 DI 10.1016/j.lungcan.2007.05.017 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 221SW UT WOS:000250248600014 PM 17610986 ER PT J AU Mandeville, JB Leite, FP Marota, JJA AF Mandeville, Joseph B. Leite, Francisca P. Marota, John J. A. TI Spin-echo MRI underestimates functional changes in microvascular cerebral blood plasma volume using exogenous contrast agent SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; CBV; spin echoes; iron; bold ID GRADIENT-ECHO; CBV RESPONSES; HUMAN BRAIN; FMRI; BOLD; RAT; STIMULATION; REMIFENTANIL; SPECIFICITY; SENSITIVITY AB While most functional MRI studies using exogenous contrast agent employ gradient-echo (GE) signal, spin echo (SE) imaging would represent an attractive alternative if its detection power were more comparable with GE imaging. This study demonstrates that SE methods systematically underestimate functional changes in microvascular cerebral blood plasma volume (CBV), so that SE detection power in brain tissue cannot match that provided by GE signal. Empirically, the in vivo response of SE-CBV was about 40% smaller than that of GE-CBV in rat brain at low basal values of CBV, a result that is consistent with physics predictions under the simplifying assumption of uniform vessel dilation. However, increasing values of basal CBV were associated with monotonically increasing mean vessel sizes and monotonically decreasing GE to SE ratios of functional changes in CBV (fCBV). This result suggests the presence of large but weakly reactive conduit vessels at high basal values of CBV. Hence, we conclude that GE imaging is the method of choice for functional MRI (fMRI) using exogenous contrast agent in most cases, although SE methods may represent a more spatially linear representation of underlying neural activity that becomes most apparent in regions with high basal CBV, such as the cortical surface. C1 Harvard Univ, MIT, Massachusetts Gen Hosp, MGH,HMS,Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Mandeville, JB (reprint author), Massachusetts Gen Hosp, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. EM jbm@nmr.mgh.harvard.edu OI Leite, Francisca/0000-0003-2550-2616 FU NIBIB NIH HHS [R01-EB001782]; NIDA NIH HHS [K08-DA14665]; PHS HHS [R0I-B000790] NR 35 TC 7 Z9 7 U1 0 U2 1 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 2007 VL 58 IS 4 BP 769 EP 776 DI 10.1002/mrm.21380 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216AD UT WOS:000249849200015 PM 17899605 ER PT J AU Pohl, KM Fisher, J Bouix, S Shenton, M McCarley, RW Grimson, WEL Kikinis, R Wells, WM AF Pohl, Kilian M. Fisher, John Bouix, Sylvain Shenton, Martha McCarley, Robert W. Grimson, W. Eric L. Kikinis, Ron Wells, William M. TI Using the logarithm of odds to define a vector space on probabilistic atlases SO MEDICAL IMAGE ANALYSIS LA English DT Article; Proceedings Paper CT 9th International Conference on Computing and Computer-Assisted Intervention CY OCT 01-06, 2006 CL Copenhagen, DENMARK SP AstraZeneca, Ctr Clin & Basic Res, Claron, Elsevier, GE, Medtronic, No Digital Inc, Siemens Corp Res, Springer, Visiopharm DE logarithm of odds; logistic function; anatomical variations; shape representation; distance map; Bayesian modeling; interpolation; statistical classification ID SEGMENTATION; SHAPE; REGISTRATION; IMAGES; MODELS AB The logarithm of the odds ratio (LogOdds) is frequently used in areas such as artificial neural networks, economics, and biology, as an alternative representation of probabilities. Here, we use LogOdds to place probabilistic atlases in a linear vector space. This representation has several useful properties for medical imaging. For example, it not only encodes the shape of multiple anatomical structures but also captures some information concerning uncertainty. We demonstrate that the resulting vector space operations of addition and scalar multiplication have natural probabilistic interpretations. We discuss several examples for placing label maps into the space of LogOdds. First, we relate signed distance maps, a widely used implicit shape representation, to LogOdds and compare it to an alternative that is based on smoothing by spatial Gaussians. We find that the LogOdds approach better preserves shapes in a complex multiple object setting. In the second example, we capture the uncertainty of boundary locations by mapping multiple label maps of the same object into the LogOdds space. Third, we define a framework for non-convex interpolations among atlases that capture different time points in the aging process of a population. We evaluate the accuracy of our representation by generating a deformable shape atlas that captures the variations of anatomical shapes across a population. The deformable atlas is the result of a principal component analysis within the LogOdds space. This atlas is integrated into an existing segmentation approach for MR images. We compare the performance of the resulting implementation in segmenting 20 test cases to a similar approach that uses a more standard shape model that is based on signed distance maps. On this data set, the Bayesian classification model with our new representation outperformed the other approaches in segmenting subcortical structures. (C) 2007 Elsevier B.V. All rights reserved. C1 MIT, Comp Sci & Artifical Intelligence Lab, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Surg Planning Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat,Psychiat Neuroimaging Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, W Roxbury, MA 02132 USA. VA Boston Healthcare Syst, Dept Psychiat, Boston, MA 02132 USA. RP Pohl, KM (reprint author), MIT, Comp Sci & Artifical Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM pohl@csail.mit.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Bouix, Sylvain/0000-0003-1326-6054 FU NCRR NIH HHS [P41 RR013218, P41 RR013218-10, P41-RR13218, U24 RR021382, U24 RR021382-03, U24-RR021382, U41 RR019703, U41 RR019703-03, U41-RR019703]; NIAAA NIH HHS [R01 AA016748, R01 AA016748-01]; NIBIB NIH HHS [U54 EB005149, U54 EB005149-04]; NIEHS NIH HHS [27302C0031]; NIMH NIH HHS [R01 MH 40799, K05 MH 70047, K05 MH070047, K05 MH070047-05, R01 MH 50747, R01 MH040799]; NINDS NIH HHS [R01 NS051826, R01 NS051826-03, R01-NS051826] NR 35 TC 48 Z9 48 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 J9 MED IMAGE ANAL JI Med. Image Anal. PD OCT PY 2007 VL 11 IS 5 BP 465 EP 477 DI 10.1016/j.media.2007.06.003 PG 13 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 223UV UT WOS:000250398800006 PM 17698403 ER PT J AU Lu, HM Brett, R Engelsman, M Slopsema, R Kooy, H Flanz, J AF Lu, Hsiao-Ming Brett, Robert Engelsman, Martijn Slopsema, Roelf Kooy, Hanne Flanz, Jay TI Sensitivities in the production of spread-out Bragg peak dose distributions by passive scattering with beam current modulation SO MEDICAL PHYSICS LA English DT Article ID PROTON; FIELDS; DESIGN AB A spread-out Bragg peak (SOBP) is used in proton beam therapy to create a longitudinal conformality of the required dose to the target. In order to create this effect in a passive beam scattering system, a variety of components must operate in conjunction to produce the desired beam parameters. We will describe how the SOBP is generated and will explore the tolerances of the various components and their subsequent effect on the dose distribution. A specific aspect of this investigation includes a case study involving the use. of a beam current modulated system. In such a system, the intensity of the beam current can be varied in synchronization with the revolution of the range-modulator wheel. As a result, the weights of the pulled-back Bragg peaks can be individually controlled to produce uniform dose plateaus for a large range of treatment depths using only a small number of modulator wheels. (C) 2007 American Association of Physicists in Medicine. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. RP Lu, HM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. FU NCI NIH HHS [5P01 CA 21239-24] NR 9 TC 10 Z9 10 U1 0 U2 1 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 2007 VL 34 IS 10 BP 3844 EP 3853 DI 10.1118/1.2776255 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 222WY UT WOS:000250330100017 PM 17985630 ER PT J AU Ionascu, D Jiang, SB Nishioka, S Shirato, H Berbeco, RI AF Ionascu, Dan Jiang, Steve B. Nishioka, Seiko Shirato, Hiroki Berbeco, Ross I. TI Internal-external correlation investigations of respiratory induced motion of lung tumors SO MEDICAL PHYSICS LA English DT Article DE respiratory tumor motion; implanted fiducial; external suroggate; correlation; time shift; amplitude mismatch; lung cancer ID REAL-TIME TUMOR; TRANSTHORACIC NEEDLE-BIOPSY; GATED RADIATION-THERAPY; TRACKING RADIOTHERAPY; PULMONARY NODULES; CT; PNEUMOTHORAX; FEASIBILITY; ASPIRATION; PREDICTION AB In gated radiation therapy procedures, the lung tumor position is used directly (by implanted radiopaque markers) or indirectly (by external surrogate methods) to decrease the volume of irradiated healthy tissue. Due to a risk of pneumothorax, many clinics do not implant fiducials, and the gated treatment is primarily based on a respiratory induced external signal. The external surrogate method relies upon the assumption that the internal tumor motion is well correlated with the external respiratory induced motion, and that this correlation is constant in time. Using a set of data that contains synchronous internal and external motion traces, we have developed a dynamic data analysis technique to study the internal-external correlation, and to quantitatively estimate its underlying time behavior. The work presented here quantifies the time dependent behavior of the correlation between external respiratory signals and lung implanted fiducial motion. The corresponding amplitude mismatch is also reported for the, lung patients studied. The information obtained can be used to improve the accuracy of tumor tracking. For the ten patients in this study, the SI internal-external motion is well correlated, with small time shifts and corresponding amplitude mismatches. Although the AP internal -external motion reveals larger time shifts than along the SI direction, the corresponding amplitude mismatches are below 5 mm. (C) 2007 American Association of Physicists in Medicine. C1 Dana Farber Brigham & Womens Canc Ctr, Div Med Phys, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif San Diego, San Diego Moores Canc Ctr, Dept Radiat Oncol, La Jolla, CA 92093 USA. NTT, E Japan Sapporo Hosp, Sapporo, Hokkaido, Japan. Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan. RP Ionascu, D (reprint author), Dana Farber Brigham & Womens Canc Ctr, Div Med Phys, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. RI Shirato, Hiroki/A-7068-2010 NR 31 TC 111 Z9 114 U1 1 U2 11 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 2007 VL 34 IS 10 BP 3893 EP 3903 DI 10.1118/1.2779941 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 222WY UT WOS:000250330100022 PM 17985635 ER PT J AU Wang, BB Doench, JG Novina, CD AF Wang, Bingbing Doench, John G. Novina, Carl D. TI Analysis of microRNA effector functions in vitro SO METHODS LA English DT Article DE MicroRNA; siRNA; RNA interference; translation; cell-free; gene silencing ID MESSENGER-RNA DEGRADATION; INTERNAL RIBOSOMAL ENTRY; TRANSLATION INITIATION; PROTEIN-SYNTHESIS; DEPENDENT LOCALIZATION; MICROPROCESSOR COMPLEX; CAENORHABDITIS-ELEGANS; MAMMALIAN-CELLS; HEPATITIS-C; HUMAN DICER AB Analyses of gene functions in vitro provide the means to dissect biological phenomena. Development of cell-free assays for transcription, splicing, and translation has yielded great insights into macromolecular interactions and functions required for these processes. This article discusses development of cell-free assays to test macromolecular interactions and activities required for microRNA effector functions. This chapter also compares in vitro analyses to complementary studies in cells and the technical considerations that permit molecular analysis of microRNA function in cell-free conditions. (C) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Proteom, Cambridge, MA 02141 USA. Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Novina, CD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM carl_novina@dfci.harvard.edu OI Doench, John/0000-0002-3707-9889 NR 85 TC 17 Z9 18 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD OCT PY 2007 VL 43 IS 2 BP 91 EP 104 DI 10.1016/j.ymeth.2007.04.003 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 225UC UT WOS:000250542500002 PM 17889795 ER PT J AU Matsunaga, J Medeiros, MA Sanchez, Y Werneid, KF Ko, AI AF Matsunaga, James Medeiros, Marco A. Sanchez, Yolanda Werneid, Kristian F. Ko, Albert I. TI Osmotic regulation of expression of two extracellular matrix-binding proteins and a haemolysin of Leptospira interrogans: differential effects on LigA and Sph2 extracellular release SO MICROBIOLOGY-SGM LA English DT Article ID SURFACE-EXPOSED LIPOPROTEIN; SEROVAR LAI; OUTER-MEMBRANE; MOLECULAR CHARACTERIZATION; FILAMENTOUS HEMAGGLUTININ; BORDETELLA-PERTUSSIS; MAMMALIAN INFECTION; SIGNAL-TRANSDUCTION; MYXOCOCCUS-XANTHUS; ADENYLYL-CYCLASE AB The life cycle of the pathogen Leptospira interrogans involves stages outside and inside the host. Entry of L. interrogans from moist environments into the host is likely to be accompanied by the induction of genes encoding virulence determinants and the concomitant repression of genes encoding products required for survival outside of the host. The expression of the adhesin LigA, the haemolysin Sph2 (Lk73.5) and the outer-membrane lipoprotein LipL36 of pathogenic Leptospira species have been reported to be regulated by mammalian host signals. A previous study demonstrated that raising the osmolarity of the leptospiral growth medium to physiological levels encountered in the host by addition of various salts enhanced the levels of cell-associated LigA and LigB and extracellular LigA. In this study, we systematically examined the effects of osmotic upshift with ionic and non-ionic solutes on expression of the known mammalian host-regulated leptospiral genes. The levels of cell-associated LigA, LigB and Sph2 increased at physiological osmolarity, whereas LipL36 levels decreased, corresponding to changes in specific transcript levels. These changes in expression occurred irrespective of whether sodium chloride or sucrose was used as the solute. The increase of cellular LigA, LigB and Sph2 protein levels occurred within hours of adding sodium chloride. Extracellular Sph2 levels increased when either sodium chloride or sucrose was added to achieve physiological osmolarity. In contrast, enhanced levels of extracellular LigA were observed only with an increase in ionic strength. These results indicate that the mechanisms for release of LigA and Sph2 differ during host infection. Thus, osmolarity not only affects leptospiral gene expression by affecting transcript levels of putative virulence determinants but also affects the release of such proteins into the surroundings. C1 Res Serv, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Brazilian Minist Hlth, Oswaldo Cruz Inst, Rio De Janeiro, Brazil. Cornell Univ, Weill Med Coll, Div Int Med & Infect Dis, New York, NY 10021 USA. Brazilian Minist Hlth, Oswaldo Cruz Fdn, Goncalo Moniz Res Ctr, Salvador, BA, Brazil. RP Matsunaga, J (reprint author), Res Serv, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM jamesm@ucla.edu RI Ko, Albert/P-2343-2015 FU FIC NIH HHS [TW00919]; NIAID NIH HHS [AI052473] NR 48 TC 28 Z9 28 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD OCT PY 2007 VL 153 BP 3390 EP 3398 DI 10.1099/mic.0.2007/007948-0 PN 10 PG 9 WC Microbiology SC Microbiology GA 222ES UT WOS:000250279500019 PM 17906138 ER PT J AU Sholl, LM Iafrate, AJ Chou, YP Wu, MT Goan, YG Su, L Huang, YT Christiani, DC Chirieac, LR AF Sholl, Lynette M. Iafrate, A. John Chou, Yi-Ping Wu, Ming-Tsang Goan, Yih-Gang Su, Li Huang, Yen-Tsung Christiani, David C. Chirieac, Lucian R. TI Validation of chromogenic in situ hybridization for detection of EGFR copy number amplification in nonsmall cell lung carcinoma SO MODERN PATHOLOGY LA English DT Article DE EGFR; lung cancer; chromogenic in situ hybridization ID GROWTH-FACTOR-RECEPTOR; GEFITINIB SENSITIVITY; GENE AMPLIFICATION; PROTEIN EXPRESSION; CANCER; MUTATIONS; PREDICTORS; ADENOCARCINOMA; HER2 AB Epidermal growth factor receptor (EGFR) gene copy number correlates with response to tyrosine kinase inhibitors in patients with nonsmall cell lung carcinoma. Fluorescence in situ hybridization (FISH), a standard methodology to detect EGFR copy number abnormalities in nonsmall cell lung carcinoma, is limited by instrumentation and cost. Chromogenic in situ hybridization (CISH) is an emerging alternative detection technique using light microscopy, but its utility in assessing EGFR copy number in lung cancer is not established. To address the utility of CISH, we studied paraffin-embedded nonsmall cell lung carcinoma specimens from 77 Taiwanese nonsmoking women treated by surgery alone. We recorded the number of signals per tumor cell nucleus, correlated EGFR copy number by CISH with FISH results, and used receiver operating characteristics to identify cut-off points for the CISH results. Tumors were classified as adenocarcinoma (n = 28), mixed adenocarcinoma with bronchioloalveolar features (n = 25), bronchioloalveolar carcinoma (n = 2), squamous cell carcinoma (n = 15), and adenosquamous carcinoma (n = 7). By FISH, 29% of cases had no amplification, 18% had low polysomy, 35% had high polysomy, and 12% had gene amplification. EGFR copy number detected by CISH highly correlated with FISH (Spearman r = 0.81, P<0.0001). We determined the optimal EGFR CISH cut-off points that discriminate between no amplification and low polysomy (2.8 signals, P = 0.09); no amplification plus low polysomy and high polysomy plus gene amplification (4.5 signals, P<0.0001); and high polysomy and gene amplification (7.1 signals, P = 0.0003). CISH is an alternative assay to FISH in determining EGFR copy number status that may contribute to stratification of patients with nonsmall cell lung carcinoma for clinical trials and identify a subset of patients that should be treated with tyrosine kinase inhibitors. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Kaohsiung Vet Gen Hosp, Dept Chest Surg, Kaohsiung, Taiwan. Kaohsiung Med Univ Hosp, Grad Inst Occupat Safety & Hlth, Dept Family Med, Kaohsiung, Taiwan. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulmonary & Crit Care Unit, Boston, MA 02115 USA. RP Chirieac, LR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM lchirieac@partners.org RI Wu, Ming-Tsang/D-2385-2009; Huang, Yen-Tsung/I-1003-2014 FU NCI NIH HHS [CA90578, CA074386, CA092824] NR 25 TC 38 Z9 39 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2007 VL 20 IS 10 BP 1028 EP 1035 DI 10.1038/modpathol.3800946 PG 8 WC Pathology SC Pathology GA 212GT UT WOS:000249583000003 PM 17673923 ER PT J AU Bosse, T Ehinger, J Czuchra, A Benesch, S Steffen, A Wu, XW Schloen, K Niemann, HH Scita, G Stradal, TEB Brakebusch, C Rottner, K AF Bosse, Tanja Ehinger, Julia Czuchra, Aleksandra Benesch, Stefanie Steffen, Anika Wu, Xunwei Schloen, Kathrin Niemann, Hartmut H. Scita, Giorgio Stradal, Theresia E. B. Brakebusch, Cord Rottner, Klemens TI Cdc42 and phosphoinositide 3-kinase drive Rac-mediated actin polymerization downstream of c-met in distinct and common pathways SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; RHO-FAMILY GTPASES; PROTEIN-KINASE-B; LISTERIA-MONOCYTOGENES; N-WASP; CELL-MIGRATION; GROWTH-FACTOR; FILOPODIUM FORMATION; DIRECTED MIGRATION; PEDESTAL FORMATION AB Activation of c-Met, the hepatocyte growth factor (HGF)/scatter factor receptor induces reorganization of the actin cytoskeleton, which drives epithelial cell scattering and motility and is exploited by pathogenic Listeria monocytogenes to invade nonepithelial cells. However, the precise contributions of distinct Rho-GTPases, the phosphatidylinositol 3-kinases, and actin assembly regulators to c-Met-mediated actin reorganization are still elusive. Here we report that HGF-induced membrane ruffling and Listeria invasion mediated by the bacterial c-Met ligand internalin B (InIB) were significantly impaired but not abrogated upon genetic removal of either Cdc42 or pharmacological inhibition of phosphoinositide 3-kinase (PI3-kinase). While loss of Cdc42 or PI3-kinase function correlated with reduced HGF- and InIB-triggered Rac activation, complete abolishment of actin reorganization and Rae activation required the simultaneous inactivation of both Cdc42 and PI3-kinase signaling. Moreover, Cdc42 activation was fully independent of PI3-kinase activity, whereas the latter partly depended on Cdc42. Finally, Cdc42 function did not require its interaction with the actin nucleation-promoting factor N-WASP. Instead, actin polymerization was driven by Arp2/3 complex activation through the WAVE complex downstream of Rac. Together, our data establish an intricate signaling network comprising as key molecules Cdc42 and PI3-kinase, which converge on Rac-mediated actin reorganization essential for Listeria invasion and membrane ruffling downstream of c-Met. C1 Helmholtz Ctr Infect Res, Cytoskeleton Dynam, D-38124 Braunschweig, Germany. Helmholtz Ctr Infect Res, Signalling & Motil Grp, D-38124 Braunschweig, Germany. Helmholtz Ctr Infect Res, Div Struct Biol, D-38124 Braunschweig, Germany. Inst Mol Biol, A-1030 Vienna, Austria. CNRS, Inst Curie, Cytoskeleton & Membrane Dynam Grp, UMR 144, F-75248 Paris, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutan Biol Res Ctr, Charlestown, MA 02129 USA. Univ Copenhagen, Dept Mol Pathol, DK-2100 Copenhagen, Denmark. Max Planck Inst Biochem, Heisenberg Grp Regulat Cytoskeletal Org, D-82152 Martinsried, Germany. European Inst Oncol, FIRC Inst Mol Oncol, I-20139 Milan, Italy. RP Rottner, K (reprint author), Helmholtz Ctr Infect Res, Cytoskeleton Dynam, Inhoffenstrasse 7, D-38124 Braunschweig, Germany. EM klemens.rottner@helmholtz-hzi.de RI Niemann, Hartmut/F-7947-2011; OI Scita, Giorgio/0000-0001-7984-1889; Rottner, Klemens/0000-0003-4244-4198 NR 59 TC 29 Z9 29 U1 0 U2 6 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 2007 VL 27 IS 19 BP 6615 EP 6628 DI 10.1128/MCB.00367-07 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 213CD UT WOS:000249642600004 PM 17682062 ER PT J AU Fotiadou, PP Takahashi, C Rajabi, HN Ewen, ME AF Fotiadou, Poppy P. Takahashi, Chiaki Rajabi, Hasan N. Ewen, Mark E. TI Wild-type NRas and KRas perform distinct functions during transformation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID C-N-RAS; K-RAS; CELL-MIGRATION; RHO-GTPASES; H-RAS; PLASMA-MEMBRANE; PROTEIN-KINASE; CAAX MOTIF; ADHESION; TUMOR AB The ras proto-oncogenes, of which there are four isoforms, are molecular switches that function in signal transduction pathways to control cell differentiation, proliferation, and survival. How the Ras isoforms orchestrate cellular processes that affect behavior is poorly understood. Further, why cells express two or more Ras isoforms is unknown. Here, using a genetically defined system, we show that the presence of both wild-type KRas and NRas isoforms is required for transformation because they perform distinct nonoverlapping functions: wild-type NRas regulates adhesion, and KRas coordinates motility. Remarkably, we find that Ras isoforms achieve functional specificity by engaging different signaling pathways to affect the same cellular processes, thereby coordinating cellular outcome. Although we find that signaling from both isoforms intersects in actin and microtubule cytoskeletons, our results suggest that KRas signals through Akt and Cdc42 while NRas signals through Raf and RhoA. Our analyses suggest a previously unappreciated convergence of different Ras isoforms on the dynamics of the processes involved in transformation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Kyoto Univ, Grad Sch Med, Dept Mol Oncol, 21st Century Ctr Excellence Program, Kyoto 606, Japan. RP Ewen, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM mark-ewen@dfci.harvard.edu FU NCI NIH HHS [R01 CA065842-13, R01 CA065842] NR 58 TC 20 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2007 VL 27 IS 19 BP 6742 EP 6755 DI 10.1128/MCB.00234-07 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 213CD UT WOS:000249642600014 PM 17636015 ER PT J AU Ivanov, GS Ivanova, T Kurash, J Ivanov, A Chuikov, S Gizatullin, F Herrera-Medina, EM Rauscher, F Reinberg, D Barlev, NA AF Ivanov, Gleb S. Ivanova, Tatyana Kurash, Julia Ivanov, Alexey Chuikov, Sergey Gizatullin, Farid Herrera-Medina, Enrique M. Rauscher, Frank, III Reinberg, Danny Barlev, Nickolai A. TI Methylation-acetylation interplay activates p53 in response to DNA damage SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID IN-VIVO; HISTONE H3; GENE-EXPRESSION; POSTTRANSLATIONAL MODIFICATIONS; TRANSCRIPTIONAL ACTIVATION; DEPENDENT ACETYLATION; LYSINE-4 METHYLATION; G(2)/M PROMOTERS; PHOSPHORYLATION; BINDING AB p53, an important tumor suppressor protein, exerts its function mostly as a sequence-specific transcription factor and is subjected to multiple posttranslational modifications in response to genotoxic stress. Recently, we discovered that lysine methylation of p53 at K372 by Set7/9 (also known as SET7 and Set9) is important for transcriptional activation and stabilization of p53. In this report we provide a molecular mechanism for the effect of p53 methylation on transcription. We demonstrate that Set7/9 activity toward p53, but not the nucleosomal histones, is modulated by DNA damage. Significantly, we show that lysine methylation of p53 is important for its subsequent acetylation, resulting in stabilization of the p53 protein. These p53 modification events can be observed on the promoter of p21 gene, a known transcriptional target of p53. Finally, we show that methylation-acetylation interplay in p53 augments acetylation of histone H4 in the promoter of p21 gene, resulting in its subsequent transcriptional activation and, hence, cell cycle arrest. Collectively, these results suggest that the cross talk between lysine methylation and acetylation is critical for p53 activation in response to DNA damage and that Set7/9 may play an important role in tumor suppression. C1 Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Univ Med & Dent New Jersey, HHMI, Piscataway, NJ 08854 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Barlev, NA (reprint author), Tufts Univ New England Med Ctr, Mol Oncol Res Inst, 75 Kneeland St, Boston, MA 02111 USA. EM nbarlev@tufts-nemc.org RI Ivanov, Alexey/I-9445-2012 NR 62 TC 96 Z9 102 U1 1 U2 10 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 2007 VL 27 IS 19 BP 6756 EP 6769 DI 10.1128/MCB.00460-07 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 213CD UT WOS:000249642600015 PM 17646389 ER PT J AU Bezy, O Vernochet, C Gesta, S Farmer, SR Kahn, CR AF Bezy, Olivier Vernochet, Cecile Gesta, Stephane Farmer, Stephen R. Kahn, C. Ronald TI TRB3 blocks adipocyte differentiation through the inhibition of C/EBP beta transcriptional activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BINDING-PROTEIN-BETA; MITOTIC CLONAL EXPANSION; ACTIVATED RECEPTOR-GAMMA; 3T3-L1 PREADIPOCYTES; INSULIN-RECEPTOR; GENE-EXPRESSION; DNA-BINDING; PPAR-GAMMA; CELL-DEATH; ADIPOGENESIS AB TRB3 has been implicated in the regulation of several biological processes in mammalian cells through its ability to influence Akt and other signaling pathways. In this study, we investigated the role of TRB3 in regulating adipogenesis and the activity of adipogenic transcription factors. We find that TRB3 is expressed in 3T3-L1 preadipocytes, and this expression is transiently suppressed during the initial days of differentiation concomitant with induction of C/EBP beta. This event appears to be a prerequisite for adipogenesis. Overexpression of TRB3 blocks differentiation of 3T3-L1 cells at a step downstream of C/EBP beta. Ectopic expression of TRB3 in mouse fibroblasts also inhibits the C/EBP beta-dependent induction of PPAR gamma 2 and blocks their differentiation into adipocytes. This inhibition of preadipocyte differentiation by TRB3 appears to be the result of two complementary effects. First, TRB3 inhibits extracellular signal-regulated kinase activity, which prevents the phosphorylation of regulatory sites on C/EBP beta. Second, TRB3 directly interacts with the DR1 domain of C/EBP beta in the nucleus, further inhibiting both its ability to bind its response element and its ability to transactivate the C/EBP alpha and a-FABP promoters. Thus, TRB3 is an important negative regulator of adipogenesis that acts at an early step in the differentiation cascade to block the C/EBP beta proadipogenic function. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Obes & Hormone Act, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Obes & Hormone Act, One Joslin Place, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [DK33201, DK34834, DK55545, R01 DK033201, R01 DK055545] NR 61 TC 54 Z9 60 U1 0 U2 4 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 2007 VL 27 IS 19 BP 6818 EP 6831 DI 10.1128/MCB.00375-07 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 213CD UT WOS:000249642600020 PM 17646392 ER PT J AU Matsumura, K Chang, BHJ Fujimiya, M Chen, WQ Kulkarni, RN Eguchi, Y Kimura, H Kojima, H Chan, L AF Matsumura, Kazuhiro Chang, Benny Hung-Junn Fujimiya, Mineko Chen, Weiqin Kulkarni, Rohit N. Eguchi, Yutaka Kimura, Hiroshi Kojima, Hideto Chan, Lawrence TI Aquaporin 7 is a beta-cell protein and regulator of intraislet glycerol content and glycerol kinase activity, beta-cell mass, and insulin production and secretion (vol 27, pg 6026, 2007) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 Baylor Coll Med, Dept Med, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA. Shiga Univ Med Sci, Dept Mol Genet Med, Dept Anat, Otsu, Shiga 52021, Japan. Shiga Univ Med Sci, Dept Crit & Intens Care Med, Otsu, Shiga 52021, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Matsumura, K (reprint author), Baylor Coll Med, Dept Med, Div Diabet Endocrinol & Metab, 1 Bayor Plaza, Houston, TX 77030 USA. NR 1 TC 1 Z9 1 U1 0 U2 1 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 2007 VL 27 IS 20 BP 7354 EP 7354 DI 10.1128/MCB.01525-07 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 219QN UT WOS:000250099800031 ER PT J AU Mills, CD Allchorne, AJ Griffin, RS Woolf, CJ Costigan, M AF Mills, Charles D. Allchorne, Andrew J. Griffin, Robert S. Woolf, Clifford J. Costigan, Michael TI GDNF selectively promotes regeneration of injury-primed sensory neurons in the lesioned spinal cord SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID ROOT GANGLION NEURONS; MYELIN-ASSOCIATED GLYCOPROTEIN; INTRINSIC GROWTH CAPACITY; NEUROTROPHIC FACTOR GDNF; CENTRAL-NERVOUS-SYSTEM; AXONAL REGENERATION; ADULT-RAT; NEURITE OUTGROWTH; FUNCTIONAL REGENERATION; RECEPTOR COMPONENTS AB Axonal regeneration within the CNS fails due to the growth inhibitory environment and the limited intrinsic growth capacity of injured neurons. Injury to DRG peripheral axons induces expression of growth associated genes including members of the glial-derived neurotrophic factor (GDNF) signaling pathway and "preconditions" the injured cells into an active growth state, enhancing growth of their centrally projecting axons. Here, we show that preconditioning DRG neurons prior to culturing increased neurite outgrowth, which was further enhanced by GDNF in a bell-shaped growth response curve. In vivo, GDNF delivered directly to DRG cell bodies facilitated the preconditioning effect, further enhancing axonal regeneration beyond spinal cord lesions. Consistent with the in vitro results, the in vivo effect was seen only at low GDNF concentrations. We conclude that peripheral nerve injury upregulates GDNF signaling pathway components and that exogenous GDNF treatment selectively promotes axonal growth of injury-primed sensory neurons in a concentration-dependent fashion. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Edinburgh, Royal Dick Sch Vet Studies, Ctr Res Neurosci, Edinburgh EH9 1QH, Midlothian, Scotland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neural Plast Res Grp, Charlestown, MA 02129 USA. RP Costigan, M (reprint author), Neurocrine Biosci, 12790 El Camino Real, San Diego, CA 92130 USA. FU NIDCR NIH HHS [R01 DE017821]; NINDS NIH HHS [NS45459, F32 NS045459, NS038253, NS052623, R01 NS038253, R03 NS052623, R03 NS052623-01, R03 NS052623-02]; PHS HHS [RDE017821A] NR 60 TC 38 Z9 40 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD OCT PY 2007 VL 36 IS 2 BP 185 EP 194 DI 10.1016/j.mcn.2007.06.011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 219FI UT WOS:000250069700006 PM 17702601 ER PT J AU Juo, P Harbaugh, T Garriga, G Kaplan, JM AF Juo, Peter Harbaugh, Tom Garriga, Gian Kaplan, Joshua M. TI CDK-5 regulates the abundance of GLR-1 glutamate receptors in the ventral cord of Caenorhabditis elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; C-ELEGANS; SYNAPTIC PLASTICITY; NMDA RECEPTORS; AMPA RECEPTORS; SURFACE EXPRESSION; EPITHELIAL-CELLS; NERVE CORD; PROTEIN; LOCALIZATION AB The proline-directed kinase Cdk5 plays a role in several aspects of neuronal development. Here, we show that CDK-5 activity regulates the abundance of the glutamate receptor GLR-1 in the ventral cord of Caenorhabditis elegans and that it produces corresponding changes in GLR-1-dependent behaviors. Loss of CDK-5 activity results in decreased abundance of GLR-1 in the ventral cord, accompanied by accumulation of GLR-1 in neuronal cell bodies. Genetic analysis of cdk-5 and the clathrin adaptin unc-11 AP180 suggests that CDK-5 functions prior to endocytosis at the synapse. The scaffolding protein LIN-10/Mint-1 also regulates GLR-1 abundance in the nerve cord. CDK-5 phosphorylates LIN-10/Mint-1 in vitro and bidirectionally regulates the abundance of LIN-10/Mint-1 in the ventral cord. We propose that CDK-5 promotes the anterograde trafficking of GLR-1 and that phosphorylation of LIN-10 may play a role in this process. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. RP Juo, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM peter.juo@tufts.edu FU NINDS NIH HHS [NS32196, F32 NS010957, F32NS10957, NS59953, R01 NS032196, R01 NS059953, R01 NS059953-01, R37 NS032196, R56 NS059953] NR 58 TC 19 Z9 29 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 2007 VL 18 IS 10 BP 3883 EP 3893 DI 10.1091/mbc.E06-09-0818 PG 11 WC Cell Biology SC Cell Biology GA 216UC UT WOS:000249903500016 PM 17671168 ER PT J AU James, BP Bunch, TA Krishnamoorthy, S Perkins, LA Brower, DL AF James, Brian P. Bunch, Thomas A. Krishnamoorthy, Srinivasan Perkins, Lizabeth A. Brower, Danny L. TI Nuclear localization of the ERK MAP kinase mediated by Drosophila alpha PS2 beta PS integrin and importin-7 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; FOCAL ADHESION KINASE; CELL-CYCLE PROGRESSION; EXTRACELLULAR-MATRIX; EPIDERMAL-GROWTH; PS INTEGRINS; RECEPTOR; CORKSCREW; DOMAIN; TRANSPORT AB The control of gene expression by the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase (ERK) requires its translocation into the nucleus. In Drosophila S2 cells nuclear accumulation of diphospho-ERK (dpERK) is greatly reduced by interfering double-stranded RNA against Drosophila importin-7 (DIM-7) or by the expression of integrin mutants, either during active cell spreading or after stimulation by insulin. In both cases, total ERK phosphorylation (on Westerns) is not significantly affected, and ERK accumulates in a perinuclear ring. Tyrosine phosphorylation of DIM-7 is reduced in cells expressing integrin mutants, indicating a mechanistic link between these components. DIM-7 and integrins localize to the same actin-containing peripheral regions in spreading cells, but DIM-7 is not concentrated in paxillin-positive focal contacts or stable focal adhesions. The Corkscrew (SHP-2) tyrosine phosphatase binds DIM-7, and Corkscrew is required for the cortical localization of DIM-7. These data suggest a model in which ERK phosphorylation must be spatially coupled to integrin-mediated DIM-7 activation to make a complex that can be imported efficiently. Moreover, dpERK nuclear import can be restored in DIM-7-deficient cells by Xenopus Importin-7, demonstrating that ERK import is an evolutionarily conserved function of this protein. C1 Univ Arizona, Arizona Canc Ctr, Ctr Insect Sci, Dept Mol & Cellular Biol, Tucson, AZ 85724 USA. Univ Arizona, Arizona Canc Ctr, Dept Biochem & Mol Biophys, Tucson, AZ 85724 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Pediat Surg Res Labs, Boston, MA 02115 USA. RP Brower, DL (reprint author), Univ Arizona, Arizona Canc Ctr, Ctr Insect Sci, Dept Mol & Cellular Biol, Tucson, AZ 85724 USA. EM dbrower@email.arizona.edu FU NICHD NIH HHS [P01 HD-39942, P01 HD039942]; NIGMS NIH HHS [K12 GM-00708, K12 GM000708, R01 GM-42474, R01 GM-61707, R01 GM042474, R01 GM061707] NR 60 TC 20 Z9 20 U1 1 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 2007 VL 18 IS 10 BP 4190 EP 4199 DI 10.1091/mbc.E06-07-0659 PG 10 WC Cell Biology SC Cell Biology GA 216UC UT WOS:000249903500042 PM 17699602 ER PT J AU Kaddurah-Daouk, R McEvoy, J Baillie, RA Lee, D Yao, JK Doraiswamy, PM Krishnan, KRR AF Kaddurah-Daouk, R. McEvoy, J. Baillie, R. A. Lee, D. Yao, J. K. Doraiswamy, P. M. Krishnan, K. R. R. TI Metabolomic mapping of atypical antipsychotic effects in schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE lipidomics; metabolomics; schizophrenia; antipsychotics; metabolic profiling ID MEMBRANE PHOSPHOLIPID-METABOLISM; MAGNETIC-RESONANCE SPECTROSCOPY; COA DESATURASE ACTIVITY; FATTY-ACID-COMPOSITION; DRUGS ACTIVATE SREBP; H-1-NMR-BASED METABONOMICS; PLASMA; ROSIGLITAZONE; ABNORMALITIES; CHOLESTEROL AB Schizophrenia is associated with impairments in neurotransmitter systems and changes in neuronal membrane phospholipids. Several atypical antipsychotic drugs induce weight gain and hypertriglyceridemia. To date, there has not been a comprehensive evaluation and mapping of global lipid changes in schizophrenia, and upon treatment with antipsychotics. Such mapping could provide novel insights about disease mechanisms and metabolic side effects of therapies used for its treatment. We used a specialized metabolomics platform 'lipidomics' that quantifies over 300 polar and nonpolar lipid metabolites (across seven lipid classes) to evaluate global lipid changes in schizophrenia and upon treatment with three commonly used atypical antipsychotics. Lipid profiles were derived for 50 patients with schizophrenia before and after treatment for 2-3 weeks with olanzapine (n = 20), risperidone (n = 14) or aripiprazole (n = 16). Patients were recruited in two cohorts (study I, n = 27 and study II, n = 23) to permit an internal replication analyses. The change from baseline to post-treatment was then compared among the three drugs. Olanzapine and risperidone affected a much broader range of lipid classes than aripiprazole. Approximately 50 lipids tended to be increased with both risperidone and olanzapine and concentrations of triacylglycerols increased and free fatty acids decreased with both drugs but not with aripiprazole. Phosphatidylethanolamine concentrations that were suppressed in patients with schizophrenia were raised by all three drugs. Drug specific differences were also detected. A principal component analysis (PCA) identified baseline lipid alterations, which correlated with acute treatment response. A more definitive long-term randomized study of these drugs correlating global lipid changes with clinical outcomes could yield biomarkers that define drug-response phenotypes. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Lipom Technol Inc, Sacramento, CA USA. VA Pittsburgh Healthacare Syst, Med Res Serv, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. RP Kaddurah-Daouk, R (reprint author), Duke Univ, Med Ctr, Dept Psychiat, Box 3950, Durham, NC 27710 USA. EM kaddu001@mc.duke.edu NR 52 TC 128 Z9 136 U1 6 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2007 VL 12 IS 10 BP 934 EP 945 DI 10.1038/sj.mp.4002000 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 217AK UT WOS:000249920500011 PM 17440431 ER PT J AU Bagalkot, V Zhang, L Levy-Nissenbaum, E Jon, S Kantoff, PW Langer, R Farokhzad, OC AF Bagalkot, Vaishali Zhang, Liangfang Levy-Nissenbaum, Etgar Jon, Sangyong Kantoff, Philip W. Langer, Robert Farokhzad, Omid C. TI Quantum dot - Aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on Bi-fluorescence resonance energy transfer SO NANO LETTERS LA English DT Article ID LIVE CELLS; DNA; PROTEIN; GENE AB We report a novel quantum dot (QD)-aptamer(Apt)-doxorubicin (Dox) conjugate [QD-Apt(Dox)] as a targeted cancer imaging, therapy, and sensing system. By functionalizing the surface of fluorescent QD with the A10 RNA aptamer, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA), we developed a targeted QD imaging system (QD-Apt) that is capable of differential uptake and imaging of prostate cancer cells that express the PSMA protein. The intercalation of Dox, a widely used antineoplastic anthracycline drug with fluorescent properties, in the double-stranded stem of the A10 aptamer results in a targeted QD-Apt(Dox) conjugate with reversible self-quenching properties based on a Bi-FRET mechanism. A donor-acceptor model fluorescence resonance energy transfer (FRET) between QD and Dox and a donor-quencher model FRET between Dox and aptamer result when Dox intercalated within the A10 aptamer. This simple multifunctional nanoparticle system can deliver Dox to the targeted prostate cancer cells and sense the delivery of Dox by activating the fluorescence of QD, which concurrently images the cancer cells. We demonstrate the specificity and sensitivity of this nanoparticle conjugate as a cancer imaging, therapy and sensing system in vitro. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Nanomed & Biomat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. Gwangju Inst Sci & Technol, Dept Life Sci, Res Ctr Biomol Nanotechnol, Kwangju 500712, South Korea. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Jon, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Nanomed & Biomat, Boston, MA 02115 USA. EM syjon@gist.ae.kr; ofarokhzad@zeus.bwh.harvard.edu RI Jon, Sangyong/C-3725-2012; bagalkot, vaishali/D-5603-2015; Dong, Ping/H-4011-2016 OI bagalkot, vaishali/0000-0002-6135-6698; FU NCI NIH HHS [CA119349]; NIBIB NIH HHS [EB003647] NR 20 TC 552 Z9 567 U1 60 U2 447 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD OCT PY 2007 VL 7 IS 10 BP 3065 EP 3070 DI 10.1021/nl071546n PG 6 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 220FU UT WOS:000250143400023 PM 17854227 ER PT J AU Yildirim, MA Goh, KI Cusick, ME Barabasi, AL Vidal, M AF Yildirim, Muhammed A. Goh, Kwang-Il Cusick, Michael E. Barabasi, Albert-Laszlo Vidal, Marc TI Drug-target network SO NATURE BIOTECHNOLOGY LA English DT Article ID PROTEIN INTERACTION NETWORK; TRANSCRIPTIONAL REGULATORY NETWORKS; HUMAN-DISEASE; DRUGGABLE GENOME; DISCOVERY; GENES; EVOLUTION; RESOURCE; BIOLOGY; DISORDERS AB The global set of relationships between protein targets of all drugs and all disease-gene products in the human protein-protein interaction or 'interactome' network remains uncharacterized. We built a bipartite graph composed of US Food and Drug Administration-approved drugs and proteins linked by drug-target binary associations. The resulting network connects most drugs into a highly interlinked giant component, with strong local clustering of drugs of similar types according to Anatomical Therapeutic Chemical classification. Topological analyses of this network quantitatively showed an overabundance of 'follow-on' drugs, that is, drugs that target already targeted proteins. By including drugs currently under investigation, we identified a trend toward more functionally diverse targets improving polypharmacology. To analyze the relationships between drug targets and disease-gene products, we measured the shortest distance between both sets of proteins in current models of the human interactome network. Significant differences in distance were found between etiological and palliative drugs. A recent trend toward more rational drug design was observed. C1 Harvard Univ, Sch Med, CCSB, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA. Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. Korea Univ, Dept Phys, Seoul 136713, South Korea. Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA. Northeastern Univ, Dept Phys, Boston, MA 02115 USA. Northeastern Univ, Dept Comp Sci & Biol, Boston, MA 02115 USA. RP Barabasi, AL (reprint author), Harvard Univ, Sch Med, CCSB, 44 Binney St, Boston, MA 02115 USA. EM alb@nd.edu; marc_vidal@dfci.harvard.edu RI Yildirim, Muhammed/J-3695-2014 OI Yildirim, Muhammed/0000-0003-2826-1766 FU NCI NIH HHS [U56 CA113004]; NHGRI NIH HHS [2R01 HG001715]; PHS HHS [U01 A1070499-01] NR 37 TC 761 Z9 809 U1 19 U2 114 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 2007 VL 25 IS 10 BP 1119 EP 1126 DI 10.1038/nbt1338 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 221KQ UT WOS:000250226600022 PM 17921997 ER PT J AU Jones, AR Miller, M Aebersold, R Apweiler, R Ball, CA Brazma, A DeGreef, J Hardy, N Hermjakob, H Hubbard, SJ Hussey, P Igra, M Jenkins, H Julian, RK Laursen, K Oliver, SG Paton, NW Sansone, SA Sarkans, U Stoeckert, CJ Taylor, CF Whetzel, PL White, JA Spellman, P Pizarro, A AF Jones, Andrew R. Miller, Michael Aebersold, Ruedi Apweiler, Rolf Ball, Catherine A. Brazma, Alvis DeGreef, James Hardy, Nigel Hermjakob, Henning Hubbard, Simon J. Hussey, Peter Igra, Mark Jenkins, Helen Julian, Randall K., Jr. Laursen, Kent Oliver, Stephen G. Paton, Norman W. Sansone, Susanna-Assunta Sarkans, Ugis Stoeckert, Christian J., Jr. Taylor, Chris F. Whetzel, Patricia L. White, Joseph A. Spellman, Paul Pizarro, Angel TI The Functional Genomics Experiment model (FuGE): an extensible framework for standards in functional genomics SO NATURE BIOTECHNOLOGY LA English DT Article ID PROTEIN ABUNDANCE; MESSENGER-RNA; OBJECT MODEL; PROTEOMICS; REPRESENTATION; COMMUNITY; ONTOLOGY; SCALE AB The Functional Genomics Experiment data model (FuGE) has been developed to facilitate convergence of data standards for high-throughput, comprehensive analyses in biology. FuGE models the components of an experimental activity that are common across different technologies, including protocols, samples and data. FuGE provides a foundation for describing entire laboratory workflows and for the development of new data formats. The Microarray Gene Expression Data society and the Proteomics Standards Initiative have committed to using FuGE as the basis for defining their respective standards, and other standards groups, including the Metabolomics Standards Initiative, are evaluating FuGE in their development efforts. Adoption of FuGE by multiple standards bodies will enable uniform reporting of common parts of functional genomics workflows, simplify data-integration efforts and ease the burden on researchers seeking to fulfill multiple minimum reporting requirements. Such advances are important for transparent data management and mining in functional genomics and systems biology. C1 Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. Univ Manchester, Sch Comp Sci, Manchester M13 9PL, Lancs, England. Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England. Rosetta Biosoftware, Seattle, WA 98109 USA. Inst Mol Syst Biol, HPT E 78, CH-8093 Zurich, Switzerland. Univ Zurich, Fac Sci, CH-8006 Zurich, Switzerland. Swiss Fed Inst Technol, Ctr Syst Physiol & Metab Dis, Zurich, Switzerland. Inst Syst Biol, Seattle, WA 98103 USA. European Bioinformat Inst, Cambridge CB10 1SD, England. Stanford Univ, Sch Med, Dept Biochem, CCSR, Stanford, CA 94305 USA. GenoLog Life Sci Software, Victoria, BC V8Z 7X8, Canada. Aberystwyth Univ, Dept Comp Sci, Aberystwyth SY23 3DB, Dyfed, Wales. LabKey Software, Seattle, WA 98103 USA. Indigo BioSyst Inc, Carmel, IN 46032 USA. Univ Penn, Ctr Bioinformat, Dept Genet, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. RP Pizarro, A (reprint author), Univ Penn, Inst Translat Med & Therapeut, 421 Curie Blvd, Philadelphia, PA 19104 USA. EM angel@mail.med.upenn.edu RI Hubbard, Simon/B-9006-2009; Smith, Barry/A-9525-2011; OI Sansone, Susanna-Assunta/0000-0001-5306-5690; Smith, Barry/0000-0003-1384-116X; Hermjakob, Henning/0000-0001-8479-0262; Apweiler, Rolf/0000-0001-7078-200X; Pizarro, Angel/0000-0003-2263-2255; Paton, Norman/0000-0003-2008-6617; Taylor, Christopher/0000-0002-9666-798X; Brazma, Alvis/0000-0001-5988-7409; Sarkans, Ugis/0000-0001-9227-8488; Hubbard, Simon/0000-0002-8601-9524; Jones, Andrew/0000-0001-6118-9327 FU Biotechnology and Biological Sciences Research Council [BB/E025080/1, BBS/B/12407, BBS/B/17204]; NHGRI NIH HHS [1P41HG003619] NR 22 TC 63 Z9 66 U1 1 U2 2 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 2007 VL 25 IS 10 BP 1127 EP 1133 DI 10.1038/nbt1347 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 221KQ UT WOS:000250226600023 PM 17921998 ER PT J AU Halperin, F Anderson, RJ Mulder, JE AF Halperin, Florencia Anderson, Ronald J. Mulder, Jean E. TI Tumor-induced osteomalacia: the importance of measuring serum phosphorus levels SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Article DE fibroblast growth factor 23; hypophosphatemia; insufficiency fractures; phosphatonin; tumor-induced osteomalacia ID HYPOPHOSPHATEMIC RICKETS; ONCOGENIC OSTEOMALACIA; PHOSPHATE HOMEOSTASIS; MESENCHYMAL TUMORS; FIBROBLAST-GROWTH-FACTOR-23 AB Background A previously healthy 32-year-old man presented with pain in his chest, ankle, and hip. His musculoskeletal pain progressed over the course of 6 months to the point of difficulty with ambulation. Investigations Radiographic studies included chest and ankle X-rays, multiple bone scans, and foot and pelvic MRI. Laboratory evaluation comprised a serum chemistry panel (including electrolyte levels, renal function tests and liver function tests), and measuring serum levels of phosphorus, parathyroid hormone, vitamin D, alkaline phosphatase, and fibroblast growth factor 23, as well as urine levels of calcium and phosphorus. Diagnosis Tumor-induced osteomalacia. Management The patient received phosphate and vitamin D supplementation in the form of potassium-phosphorus (500 mg, three times daily) and calcitriol (0.5 mu g, three times daily). Six months after his first presentation, he underwent surgical resection of a rib mass, with subsequent normalization of phosphorus concentration. C1 Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA. RP Halperin, F (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM fhalperin@partners.org NR 15 TC 6 Z9 7 U1 2 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 2007 VL 3 IS 10 BP 721 EP 725 DI 10.1038/ncpendmet0639 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 211WA UT WOS:000249552800013 PM 17893691 ER PT J AU Heist, RS Liu, G Zhou, W AF Heist, Rebecca S. Liu, Geoffrey Zhou, Wei TI Should oncologists measure the mRNA and protein expression levels of ERCC1 and RRM1 in non-small-cell lung cancer? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE biomarker; non-small-cell lung cancer; prognosis; survival C1 Merck Res Labs, Dept Epidemiol, N Wales, PA 19454 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Univ Toronto, Princess Margaret Hosp, Alan B Brown Chair Mol Genom, Toronto, ON, Canada. RP Zhou, W (reprint author), Merck Res Labs, Dept Epidemiol, UG1D-60, N Wales, PA 19454 USA. EM wei_zhou2@merck.com NR 2 TC 0 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD OCT PY 2007 VL 4 IS 10 BP 564 EP 565 DI 10.1038/ncponc0909 PG 2 WC Oncology SC Oncology GA 214AQ UT WOS:000249708800004 PM 17667918 ER PT J AU Maller, JB Fagerness, JA Reynolds, RC Neale, BM Daly, MJ Seddon, JM AF Maller, Julian B. Fagerness, Jesen A. Reynolds, Robyn C. Neale, Benjamin M. Daly, Mark J. Seddon, Johanna M. TI Variation in complement factor 3 is associated with risk of age-related macular degeneration SO NATURE GENETICS LA English DT Article ID FACTOR-H POLYMORPHISM; VARIANT; CFH; GENES; Y402H AB The association of variants in complement factors H and B with age-related macular degeneration has led to more intense genetic and functional analysis of the complement pathway. We identify a nonsynonymous coding change in complement factor 3 that is strongly associated with risk of age-related macular degeneration in a large case-control sample. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. MIT, Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. Tufts Univ New England Med Ctr, New England Eye Ctr, Ophthal Epidemiol & Genet Serv, Boston, MA 02111 USA. Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5 8AP, England. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Seddon, JM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM mjdaly@chgr.mgh.harvard.edu; jseddon@tufts-nemc.org OI Maller, Julian/0000-0002-1565-9559 FU NCRR NIH HHS [U54 RR020278]; NEI NIH HHS [N01-EY-0-2127, EY11309] NR 14 TC 249 Z9 252 U1 2 U2 8 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 2007 VL 39 IS 10 BP 1200 EP 1201 DI 10.1038/ng2131 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 214KW UT WOS:000249737400014 PM 17767156 ER PT J AU Weedon, MN Lettre, G Freathy, RM Lindgren, CM Voight, BF Perry, JRB Elliott, KS Hackett, R Guiducci, C Shields, B Zeggini, E Lango, H Lyssenko, V Timpson, NJ Burtt, NP Rayner, NW Saxena, R Ardlie, K Tobias, JH Ness, AR Ring, SM Palmer, CNA Morris, AD Peltonen, L Salomaa, V Smith, GD Groop, LC Hattersley, AT McCarthy, MI Hirschhorn, JN Frayling, TM AF Weedon, Michael N. Lettre, Guillaume Freathy, Rachel M. Lindgren, Cecilia M. Voight, Benjamin F. Perry, John R. B. Elliott, Katherine S. Hackett, Rachel Guiducci, Candace Shields, Beverley Zeggini, Eleftheria Lango, Hana Lyssenko, Valeriya Timpson, Nicholas J. Burtt, Noel P. Rayner, Nigel W. Saxena, Richa Ardlie, Kristin Tobias, Jonathan H. Ness, Andrew R. Ring, Susan M. Palmer, Colin N. A. Morris, Andrew D. Peltonen, Leena Salomaa, Veikko Smith, George Davey Groop, Leif C. Hattersley, Andrew T. McCarthy, Mark I. Hirschhorn, Joel N. Frayling, Timothy M. CA Diabet Genetics Initiative Wellcome Trust Case Control Con TI A common variant of HMGA2 is associated with adult and childhood height in the general population SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BODY HEIGHT; C GENE; RISK; HERITABILITY; DISEASE; STRATIFICATION; SUSCEPTIBILITY; METHODOLOGY; PHENOTYPE AB Human height is a classic, highly heritable quantitative trait. To begin to identify genetic variants influencing height, we examined genome-wide association data from 4,921 individuals. Common variants in the HMGA2 oncogene, exemplified by rs1042725, were associated with height (P= 4x10(-8)). HMGA2 is also a strong biological candidate for height, as rare, severe mutations in this gene alter body size in mice and humans, so we tested rs1042725 in additional samples. We confirmed the association in 19,064 adults from four further studies (P= 3x10(-11), overall P= 4x10(-16), including the genome-wide association data). We also observed the association in children (P=1x 10(-6), N= 6,827) and a tall/short case-control study (P= 4x10(-6), N=3,207). We estimate that rs1042725 explains similar to 0.3% of population variation in height (similar to 0.4 cm increased adult height per C allele). There are few examples of common genetic variants reproducibly associated with human quantitative traits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height. C1 Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX1 2LU, Devon, England. Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England. Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. Childrens Hosp, Div Genet & Endocrinol, Program Genom, Boston, MA 02115 USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Univ Oxford, Churchill Hosp, Oxford Ctr Diab Endocrinol & Metab, Oxford OX3 7LJ, England. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diab & Endocrinol, S-20502 Malmo, Sweden. Univ Helsinki, Helsinki Univ Cent Hosp,Dep Med, Folkhalsan Genet Inst,Folkhalsan Res Ctr, Res Program Mol Med, Helsinki, Finland. Univ Bristol, MRC Ctr Causal Analyses Translat Epidemiol, Bristol BS8 2PR, Avon, England. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Bristol, Clin Sci S Bristol, Bristol BS2 8AE, Avon, England. Univ Bristol, Bristol Dent Sch, Dept Oral & Dent Sci, Bristol BS1 2LY, Avon, England. Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England. Univ Dundee, Ninewells Hosp, Sch Med,Populat Pharmacogenet Grp, Biomed Res Ctr, Dundee DD1 9SY, Scotland. Univ Dundee, Ninewells Hosp, Sch Med, Div Med & Therapeut,Diab Res Grp, Dundee DD1 9SY, Scotland. Natl Publ Hlth Inst, Dept Mol Med, FI-00290 Helsinki, Finland. Univ Helsinki, Dept Med Genet, FI-00014 Helsinki, Finland. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, FI-00300 Helsinki, Finland. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Frayling, TM (reprint author), Peninsula Med Sch, Inst Biomed & Clin Sci, Magdalen Rd, Exeter EX1 2LU, Devon, England. EM Tim.Frayling@pms.ac.uk RI Palmer, Colin/C-7053-2008; Davey Smith, George/A-7407-2013; Morris, Andrew/C-2837-2009; Voight, Benjamin/F-1775-2011; Lango Allen, Hana/G-9026-2012; Ness, Andy/M-7612-2013; Tobias, Jon/E-2832-2014; Berryman, Katie/J-4236-2014; Study, GoDARTS/K-9448-2016; Fox, Laura /C-6249-2016; OI Palmer, Colin/0000-0002-6415-6560; Davey Smith, George/0000-0002-1407-8314; Freathy, Rachel/0000-0003-4152-2238; Lango Allen, Hana/0000-0002-7803-8688; Ness, Andy/0000-0003-3548-9523; Tobias, Jon/0000-0002-7475-3932; Monsalve, Beatriz Elena/0000-0002-5994-866X; Zeggini, Eleftheria/0000-0003-4238-659X; Timpson, Nicholas/0000-0002-7141-9189 FU Medical Research Council [G0500070, G0600705, G9815508, G9815508(74882)]; NHGRI NIH HHS [U01 HG004171]; Wellcome Trust [072960, 076113, 076467, 079557, 090532, GR072960] NR 30 TC 251 Z9 262 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2007 VL 39 IS 10 BP 1245 EP 1250 DI 10.1038/ng2121 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 214KW UT WOS:000249737400020 PM 17767157 ER PT J AU Phan, RT Saito, M Kitagawal, Y Means, AR Dalla-Favera, R AF Phan, Ryan T. Saito, Masumichi Kitagawal, Yukiko Means, Anthony R. Dalla-Favera, Riccardo TI Genotoxic stress regulates expression of the proto-oncogene Bc16 in germinal center B cells SO NATURE IMMUNOLOGY LA English DT Article ID PROLYL ISOMERASE PIN1; DNA-DAMAGE RESPONSE; DEREGULATED BCL6 EXPRESSION; CHROMOSOMAL TRANSLOCATIONS; TRANSCRIPTIONAL REPRESSION; LYMPHOCYTE DIFFERENTIATION; NEGATIVE AUTOREGULATION; SOMATIC HYPERMUTATION; KINASE; ATM AB Antigen-specific B cells are selected in germinal centers, the structure in which these cells proliferate while accomplishing genome-remodeling processes such as class-switch recombination and somatic hypermutation. These events are associated with considerable genotoxic stress, which cells tolerate through suppression of DNA-damage responses by Bcl-6, a transcription factor required for the formation of germinal centers. Here we show that the expression of Bcl-6 is regulated by DNA damage through a signaling pathway that promotes Bcl-6 degradation. After DNA damage accumulated, the kinase ATM promoted Bcl-6 phosphorylation, leading to its interaction with the isomerase Pin1 and its degradation by the ubiquitin-proteasome system. Because Bcl-6 is required for the maintenance of germinal centers, our findings suggest that the extent of genotoxic stress controls the fate of germinal center B cells by means of Bcl-6. C1 Columbia Univ, Herbert Irving Comprehens Canc Ctr, Inst Canc Genet, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Herbert Irving Comprehens Canc Ctr, Inst Canc Genet, Dept Genet & Dev, New York, NY 10032 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Harvard Univ, Sch Med, Childrens Hosp, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Dalla-Favera, R (reprint author), Columbia Univ, Herbert Irving Comprehens Canc Ctr, Inst Canc Genet, Dept Pathol, New York, NY 10032 USA. EM rd10@columbia.edu NR 55 TC 50 Z9 55 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2007 VL 8 IS 10 BP 1132 EP 1139 DI 10.1038/ni1508 PG 8 WC Immunology SC Immunology GA 213UA UT WOS:000249691400028 PM 17828269 ER PT J AU Chen, Z Kujawa, SG Sewell, WF AF Chen, Zhiqiang Kujawa, Sharon G. Sewell, William F. TI Auditory sensitivity regulation via rapid changes in expression of surface AMPA receptors SO NATURE NEUROSCIENCE LA English DT Article ID SYNAPTIC-TRANSMISSION; TRAFFICKING; SYNAPSES; NEURONS; INTERNALIZATION; COCHLEA; NERVE AB We report a robust regulation of surface AMPA receptors in mouse auditory neurons, both with application of glutamate receptor agonists in cultured neurons and in response to acoustic stimulation in vivo. The reversible reduction of surface AMPA receptors following acoustic stimulation correlated with changes in acoustic sensitivity. Thus we show that AMPA receptor cycling is important for optimizing synaptic transfer at one of the most exacting synapses in the body. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Sewell, WF (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM wfs@epl.meei.harvard.edu NR 15 TC 25 Z9 25 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD OCT PY 2007 VL 10 IS 10 BP 1238 EP 1240 DI 10.1038/nn1974 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 214FG UT WOS:000249720800007 PM 17828255 ER PT J AU Gerstner, E Abrey, L Schiff, D Ferreri, A Lister, A Montoto, S Tsang, R Thiel, E Graus, F Harris, N Batchelor, T AF Gerstner, Elizabeth Abrey, Lauren Schiff, David Ferreri, Andres Lister, Andrew Montoto, Silva Tsang, Richard Thiel, Eckhard Graus, Francesc Harris, Nancy Batchelor, Tracy TI CNS Hodgkin's lymphoma: An international primary CNS lymphoma collaborative group (IPCG) report of 13 cases SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Gerstner, Elizabeth; Harris, Nancy; Batchelor, Tracy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Abrey, Lauren] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Schiff, David] Univ Virginia, Charlottesville, VA USA. [Ferreri, Andres] Ist Sci San Raffaele, Milan, Italy. [Lister, Andrew; Montoto, Silva] St Bartholomews Hosp, London, England. [Tsang, Richard] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Thiel, Eckhard] Charite Campus Benjamin Franklin, Berlin, Germany. [Graus, Francesc] Hosp & Clin, Barcelona, Spain. RI Ferreri, Andres Jose Maria/A-6662-2013 OI Ferreri, Andres Jose Maria/0000-0001-9606-6124 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 478 EP 478 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100054 ER PT J AU Barker, F Curry, W AF Barker, Fred Curry, William TI Racial and socioeconomic disparities in enrollment in CTEP-sponsored brain tumor therapeutic trials SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Barker, Fred; Curry, William] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 479 EP 479 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100058 ER PT J AU Menon, LG Kim, SK Benny, O Black, P Machluf, M Carroll, R AF Menon, Lata G. Kim, Seung-Ki Benny, Ofra Black, Peter Machluf, Marcelle Carroll, Rona TI Biodegradable microspheres loaded with gleevec (STI571) inhibit the growth of human glioma tumors in an orthotopic mouse model SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Menon, Lata G.; Carroll, Rona] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kim, Seung-Ki] Seoul Natl Univ Hosp, Dept Neurosurg, Seoul 110744, South Korea. [Benny, Ofra; Machluf, Marcelle] Technion Israel Inst Technol, IL-32000 Haifa, Israel. [Black, Peter] Dana Faber Brigham & Womens Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 492 EP 492 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100105 ER PT J AU Brennan, C Wiedemeyer, R Ligon, K Futreal, PA Chin, L AF Brennan, Cameron Wiedemeyer, Ruprecht Ligon, Keith Futreal, P. Andrew Chin, Lynda TI An INK4 tumor suppressor circuit constrains glioblastoma development and promotes coordinate silencing of G1 cyclin-dependent kinase inhibitors p18INK4C and p16INK4A SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Brennan, Cameron] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wiedemeyer, Ruprecht; Chin, Lynda] Dana Faber Canc Inst, Boston, MA USA. [Ligon, Keith] Dana Faber Brigham & Womens Canc Ctr, Boston, MA USA. OI Brennan, Cameron/0000-0003-4064-8891 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 497 EP 498 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100125 ER PT J AU Norden, AD Young, G Setayesh, K Muzikansky, A Klufas, R Ross, G Drappatz, J Kesari, S Ciampa, AS Ebbeling, LG Levy, B Wen, P AF Norden, Andrew D. Young, Geoffrey Setayesh, Kian Muzikansky, Alona Klufas, Roman Ross, Gina Drappatz, Jan Kesari, Santosh Ciampa, Abigail Slate Ebbeling, Laura G. Levy, Brenda Wen, Patrick TI Retrospective study of bevacizumab for recurrent malignant gliomas and analysis of the patterns of recurrence SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Norden, Andrew D.; Drappatz, Jan; Kesari, Santosh; Ciampa, Abigail Slate; Ebbeling, Laura G.; Levy, Brenda; Wen, Patrick] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Young, Geoffrey; Setayesh, Kian; Klufas, Roman; Ross, Gina] Brigham & Womens Hosp, Harvard Med Sch, Boston, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Boston, MA USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 515 EP 516 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100193 ER PT J AU Reardon, D Groves, M Wen, P Nabors, L Mikkelsen, T Rosenfeld, S Harris, D DeMarini, D Suttle, B Arumugham, T Hodge, J Lager, J AF Reardon, David Groves, Morris Wen, Patrick Nabors, Louis Mikkelsen, Tom Rosenfeld, Steve Harris, Dean DeMarini, Douglas Suttle, Ben Arumugham, Thangam Hodge, Jeffrey Lager, Joanne TI A phase II trial of lapatinib and pazopanib for patients with recurrent glioblastoma multiforme (GBM) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Reardon, David] Duke Univ, Durham, NC USA. [Groves, Morris] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Wen, Patrick] Dana Farber Canc Inst, Boston, MA USA. [Nabors, Louis] Univ Alabama, Birmingham, AL USA. [Mikkelsen, Tom] Henry Ford Hlth Syst, Detroit, MI USA. [Rosenfeld, Steve] Columbia Univ, New York, NY USA. [Harris, Dean] Royal Marsden Hosp, Surrey, England. [Suttle, Ben; Arumugham, Thangam; Hodge, Jeffrey; Lager, Joanne] GlaxoSmithKline Inc, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 516 EP 516 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100196 ER PT J AU Reardon, D Fink, K Nabors, L Cloughesy, T O'Neill, A Schiff, D Raizer, J Krueger, S Picard, M Mikkelsen, T AF Reardon, David Fink, Karen Nabors, Louis Cloughesy, Timothy O'Neill, Alison Schiff, David Raizer, Jeffrey Krueger, Stefan Picard, Martin Mikkelsen, Tom TI An update of the phase IIA trial of cilengitide (EMD121974) single-agent therapy in patients with recurrent glioblastoma: EMD 121974-009 SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Reardon, David] Duke Univ, Med Ctr, Durham, NC USA. [Fink, Karen] Baylor Univ, Ctr Med, Dallas, TX USA. [Nabors, Louis] Univ Alabama, Birmingham, AL USA. [Cloughesy, Timothy] Univ Calif Los Angeles, Los Angeles, CA USA. [O'Neill, Alison] Massachusetts Gen Hosp, Boston, MA USA. [Schiff, David] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. [Raizer, Jeffrey] Northwestern Univ, Feinberg Sch Med, Chicago, IL USA. [Krueger, Stefan] Merck KGaA, Darmstadt, Germany. [Mikkelsen, Tom] Henry Ford Hosp, Hermelin Brain Tumor Ctr, Detroit, MI USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 517 EP 517 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100197 ER PT J AU McGarry, L Morissette, N Earle, C Liepa, A Thompson, D AF McGarry, Lisa Morissette, Nathalie Earle, Craig Liepa, Astra Thompson, David TI Patterns of initial treatment, survival, and cost for the treatment of glioblastoma multiforme (GBM): An analysis of SEER-Medicare data SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [McGarry, Lisa; Morissette, Nathalie; Thompson, David] i3 Innovus, Medford, MA USA. [Earle, Craig] Dana Farber Canc Inst, Boston, MA 02115 USA. [Liepa, Astra] Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 520 EP 520 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100209 ER PT J AU Kesari, S Schiff, D Drappatz, J Gigas, D Doherty, L Ligon, K Muzikansky, A Ciampa, A Bradshaw, J Levy, B Radakovic, G Ramakrishna, N Black, P Wen, P AF Kesari, Santosh Schiff, David Drappatz, Jan Gigas, Debra Doherty, Lisa Ligon, Keith Muzikansky, Alona Ciampa, Abgail Bradshaw, Joanna Levy, Brenda Radakovic, Gospova Ramakrishna, Naren Black, Peter Wen, Patrick TI Phase II study of prolonged daily temozolomide for low-grade gliomas in adults SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Kesari, Santosh] Soc Neuro Oncol, Boston, MA USA. [Schiff, David; Radakovic, Gospova] Univ Virginia, Charlottesville, VA USA. [Drappatz, Jan; Gigas, Debra; Doherty, Lisa; Ligon, Keith; Ciampa, Abgail; Bradshaw, Joanna; Levy, Brenda; Ramakrishna, Naren; Black, Peter; Wen, Patrick] Dana Farber Canc Inst, Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 522 EP 522 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100217 ER PT J AU Chheda, MG Barker, FG Ebb, DH Louis, DN Batchelor, TT AF Chheda, Milan G. Barker, Frederick G. Ebb, David H. Louis, David N. Batchelor, Tracy T. TI Cytoreductive chemotherapy prior to definitive resection in patients with pineal parenchymal tumors SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Chheda, Milan G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Barker, Frederick G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Ebb, David H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. [Louis, David N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Radiat Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 531 EP 531 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100249 ER PT J AU Eichler, A Kuter, I Ryan, P Schapira, L Younger, J Henson, J AF Eichler, April Kuter, Irene Ryan, Paula Schapira, Lidia Younger, Jerry Henson, John TI Her2 status predicts survival after diagnosis of brain metastasis in breast cancer SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Eichler, April; Henson, John] Massachusetts Gen Hosp, Pappas Ctr Neuro Oncol, Boston, MA 02114 USA. [Kuter, Irene; Ryan, Paula; Schapira, Lidia; Younger, Jerry] Massachusetts Gen Hosp, Gillete Ctr Womens Canc, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 544 EP 545 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100299 ER PT J AU Chi, A Batchelor, TT AF Chi, Andrew Batchelor, Tracy T. TI Low-grade gliomas in older patients - A malignant tumor? SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Chi, Andrew; Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 545 EP 545 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100300 ER PT J AU Lee, K Li, MH Eberhart, C Pomeroy, S Taylor, M Rutka, J Hawkins, C Huang, A AF Lee, Kyle Li, Meihua Eberhart, Charles Pomeroy, Scott Taylor, Michael Rutka, James Hawkins, Cynthia Huang, Annie TI Genomic analyses of pediatric supratentorial primitive neuroectodermal brain tumors SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Lee, Kyle; Li, Meihua; Huang, Annie] SickKids Hosp, Div Hematol Oncol, Toronto, ON, Canada. [Eberhart, Charles] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Pomeroy, Scott] Dana Farber Canc Ctr, Boston, MA USA. [Taylor, Michael; Rutka, James] SickKids Hosp, Toronto, ON, Canada. [Hawkins, Cynthia] SickKids Hosp, Pediat Lab Med, Toronto, ON, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 556 EP 556 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100342 ER PT J AU Lucas, M Maramaldi, P AF Lucas, Michele Maramaldi, Peter TI The impact of diagnosis and treatment on the high-grade brain tumor family SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Lucas, Michele; Maramaldi, Peter] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Maramaldi, Peter] Massachusetts Gen Hosp, Social Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 570 EP 570 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100393 ER PT J AU Turner, C Begley, H Chordas, C Cieurzo, C Rey-Casserly, C Delaney, B Cunningham, LK Pomeroy, S Ullrich, N Goumnerova, L Scott, RM Marcus, K Fletcher, W Chi, S Kieran, M AF Turner, Christopher Begley, Heather Chordas, Christine Cieurzo, Cori Rey-Casserly, Celiane Delaney, Brian Cunningham, Leslie Kim Pomeroy, Scott Ullrich, Nicole Goumnerova, Liliana Scott, R. Michael Marcus, Karen Fletcher, William Chi, Susan Kieran, Mark TI Long-term medical, psychological, and educational issues in pediatric low-grade gliomas treated with surgery only SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Turner, Christopher; Chordas, Christine; Cieurzo, Cori; Delaney, Brian; Cunningham, Leslie Kim; Fletcher, William; Chi, Susan; Kieran, Mark] Dana Farber Childrens Hosp Canc Care, Boston, MA 02115 USA. [Begley, Heather] Tufts Univ, Sch Med, Boston, MA USA. [Rey-Casserly, Celiane; Marcus, Karen] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Pomeroy, Scott; Goumnerova, Liliana] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Goumnerova, Liliana; Scott, R. Michael] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Marcus, Karen] Dana Farber Childrens Hosp Canc Care, Joint Ctr Radiat Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 572 EP 572 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100399 ER PT J AU Chen, C D'Andrea, A AF Chen, Clark D'Andrea, Alan TI A large-scale siRNA screen revealed that PARP1 and CDK7 inhibition selectively sensitized EGFR and ras over-expressing glioma cell lines to ionizing radiation SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Chen, Clark] Harvard Univ, Boston, MA 02115 USA. [D'Andrea, Alan] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 590 EP 590 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100462 ER PT J AU Wakimoto, H Farrell, C Aghi, M Martuza, R Rabkin, S AF Wakimoto, Hiroaki Farrell, Christopher Aghi, Manish Martuza, Robert Rabkin, Samuel TI Oncolytic herpes simplex virus vectors effectively kill human glioblastoma stem-like cells SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Wakimoto, Hiroaki; Farrell, Christopher; Aghi, Manish; Martuza, Robert; Rabkin, Samuel] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 597 EP 598 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100489 ER PT J AU Makris, N Papadimitriou, GM van der Kouwe, A Kennedy, DN Hodge, SM Dale, AM Benner, T Wald, LL Wu, O Tuch, DS Caviness, VS Moore, TL Killiany, RJ AF Makris, Nikos Papadimitriou, George M. van der Kouwe, Andre Kennedy, David N. Hodge, Steven M. Dale, Anders M. Benner, Thomas Wald, Lawrence L. Wu, Ona Tuch, David S. Caviness, Verne S. Moore, Tara L. Killiany, Ronald J. TI Frontal connections and cognitive changes in normal aging rhesus monkeys: A DTI study SO NEUROBIOLOGY OF AGING LA English DT Article DE DT-MRI; aging; white matter; rhesus monkey ID WHITE-MATTER MICROSTRUCTURE; DIFFUSION TENSOR; CORPUS-CALLOSUM; BRAIN IMAGES; IN-VIVO; ASSOCIATION CORTEX; CHRONIC-ALCOHOLISM; SPATIAL ATTENTION; AGE; MRI AB Recent anatomical studies have found that cortical neurons are mainly preserved during the aging process while myelin damage and even axonal loss is prominent throughout the forebrain. We used diffusion tensor imaging (DT-MRI) to evaluate the hypothesis that during the process of normal aging,white matter changes preferentially affect the integrity of long corticocortical association fiber tracts, specifically the superior longitudinal fasciculus 11 and the cingulum bundle. This would disrupt communication between the frontal lobes and other forebrain regions leading to cognitive impairments. We analyzed DT-MRI datasets from seven young and seven elderly behaviorally characterized rhesus monkeys, creating fractional anisotropy (FA) maps of the brain. Significant age-related reductions in mean FA values were found for the superior longitudinal fasciculus 11 and the cingulum, bundle, as well as the anterior corpus callosum. Comparison of these FA reductions with behavioral measures demonstrated a statistically significant linear relationship between regional EA and performance on a test of executive function. These findings support the hypothesis that alterations to the integrity of these long association pathways connecting the frontal lobe with other forebrain regions contribute to cognitive impairments in normal aging. To our knowledge this is the first investigation reporting such alterations in the aging monkey. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Ctr Morphometr Anal,HST A Martinos Ct, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol Serv,Ctr Morphometr Anal,HST A Martin, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Radiol & Cognit Neurosci, La Jolla, CA 92093 USA. RP Makris, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Ctr Morphometr Anal,HST A Martinos Ct, Bldg 149,13th St, Charlestown, MA 02129 USA. EM nikos@cma.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Kennedy, David/H-3627-2012; Wald, Lawrence/D-4151-2009; OI Moore, Tara/0000-0003-3869-3837; Moss, Mark/0000-0001-7330-3836; Rosene, Douglas/0000-0001-8719-1441 FU NCRR NIH HHS [P51-RR00165, P41-RR14075]; NIA NIH HHS [1R03-AG20829-01, P01-AG00001]; NIBIB NIH HHS [R01-EB00790-03, U54 EB05149]; NINDS NIH HHS [5R01NS38477] NR 93 TC 58 Z9 61 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD OCT PY 2007 VL 28 IS 10 BP 1556 EP 1567 DI 10.1016/j.neurobiolaging.2006.07.005 PG 12 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 204RX UT WOS:000249062800010 PM 16962214 ER PT J AU Bartzokis, G Lu, PH Tishler, TA Fong, SM Oluwadara, B Finn, JP Huang, D Bordelon, Y Mintz, J Perlman, S AF Bartzokis, George Lu, Po H. Tishler, Todd A. Fong, Sophia M. Oluwadara, Bolanle Finn, J. Paul Huang, Danny Bordelon, Yvette Mintz, Jim Perlman, Susan TI Myelin breakdown and iron changes in Huntington's disease: Pathogenesis and treatment implications SO NEUROCHEMICAL RESEARCH LA English DT Article DE brain; neurodegeneration; ferritin; FDRI; Huntingtin; BDNF; excitotoxicity; prevention; onset; oligodendrocyte ID VISUAL-CORTEX AREA-17; BRAIN FERRITIN IRON; IN-VIVO EVALUATION; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; COGNITIVE DECLINE; WHITE-MATTER; NEURODEGENERATIVE DISORDERS; NEURONAL DEGENERATION; MORPHOMETRIC-ANALYSIS AB Background Postmortem and in vivo imaging data support the hypothesis that premature myelin breakdown and subsequent homeostatic remyelination attempts with increased oligodendrocyte and iron levels may contribute to Huntington's Disease (HD) pathogenesis and the symmetrical progress of neuronal loss from earlier-myelinating striatum to later-myelinating regions. A unique combination of in vivo tissue integrity and iron level assessments was used to examine the hypothesis. Methods A method that uses two Magnetic resonance imaging (MRI) instruments operating at different field-strengths was used to quantify the iron content of ferritin molecules (ferritin iron) as well as tissue integrity in eight regions in 11 HD and a matched group of 27 healthy control subjects. Three white matter regions were selected based on their myelination pattern (early to later-myelinating) and fiber composition. These were frontal lobe white matter (Fwm) and splenium and genu of the corpus callosum (Swm and Gwm). In addition, gray matter structures were also chosen based on their myelination pattern and fiber composition. Three striatum structures were assessed [caudate, putamen, and globus pallidus (C, P, and G)] as well as two comparison gray matter regions that myelinate later in development and are relatively spared in HD [Hippocampus (Hipp) and Thalamus (Th)]. Results Compared to healthy controls, HD ferritin iron levels were significantly increased in striatum C, P, and G, decreased in Fwm and Gwm, and were unchanged in Hipp, Th, and Swm. Loss of tissue integrity was observed in C, P, Fwm, and especially Swm but not Hipp, Th, G, or Gwm. This pattern of findings was largely preserved when a small subset of HD subjects early in the disease process was examined. Conclusions The data suggest early in the HD process, myelin breakdown and changes in ferritin iron distribution underlie the pattern of regional toxicity observed in HD. Prospective studies are needed to verify myelin breakdown and increased iron levels are causal factors in HD pathogenesis. Tracking the effects of novel interventions that reduce myelin breakdown and iron accumulation in preclinical stages of HD could hasten the development of preventive treatments. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Div Brain Mapping, Dept Neurol, Lab Neuroimaging, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Neurosci Interdept Grad Program, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NIA NIH HHS [AG 16570, R01 AG027342]; NIMH NIH HHS [MH066029-01A2, MH51928, MH6357-01A1] NR 97 TC 99 Z9 101 U1 1 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD OCT PY 2007 VL 32 IS 10 BP 1655 EP 1664 DI 10.1007/s11064-007-9352-7 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 212FH UT WOS:000249578500005 PM 17484051 ER PT J AU Buckner, RL Vincent, JL AF Buckner, Randy L. Vincent, Justin L. TI Unrest at rest: Default activity and spontaneous network correlations SO NEUROIMAGE LA English DT Editorial Material ID FUNCTIONAL MAGNETIC-RESONANCE; BOLD SIGNAL FLUCTUATIONS; ALZHEIMERS-DISEASE; BRAIN-FUNCTION; STATE NETWORKS; PARIETAL CORTEX; WORKING-MEMORY; NEURAL BASIS; BASE-LINE; CONNECTIVITY AB A series of recent empirical observations demonstrate structured activity patterns that exist during passive task states. One observation is that a network of regions, referred to as the default network, shows preferentially greater activity during passive task states as compared to a wide range of active tasks. The second observation is that distributed regions spontaneously increase and decrease their activity together within functional-anatomic networks, even under anesthesia. We believe these rest activity patterns may reflect neural functions that consolidate the past, stabilize brain ensembles, and prepare us for the future. Accumulating data further suggest that differences in rest activity may be relevant to understanding clinical conditions such as Alzheimer's disease and autism. Maps of spontaneous network correlations also provide tools for functional localization and study of comparative anatomy between primate species. For all of these reasons, we advocate the systematic exploration of rest activity. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Buckner, RL (reprint author), Harvard Univ, Dept Psychol, Ctr Brain Sci, William James Hall,2nd Floor,33 Kirkland St, Cambridge, MA 02138 USA. EM rbuckner@wjh.harvard.edu RI Vincent, Justin/B-5033-2012 NR 60 TC 276 Z9 280 U1 4 U2 23 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 2007 VL 37 IS 4 BP 1091 EP 1096 DI 10.1016/j.neuroimage.2007.01.010 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 214YF UT WOS:000249773600013 PM 17368915 ER PT J AU Makris, N Papadimitriou, GM Sorg, S Kennedy, DN Caviness, VS Pandya, DN AF Makris, Nikos Papadimitriou, George M. Sorg, Scott Kennedy, David N. Caviness, Verne S. Pandya, Deepak N. TI The occipitofrontal fascicle in humans: A quantitative, in vivo, DT-MRI study SO NEUROIMAGE LA English DT Article DE DT-MRI; segmentation; tractography; occipitofrontal fascicle; fronto-occipital fascicle ID WHITE-MATTER; PREFRONTAL CORTEX; HUMAN BRAIN; TOPOGRAPHIC PARCELLATION; ASSOCIATION PATHWAYS; MONKEY; PROJECTIONS; CINGULUM; NUCLEI; SYSTEM AB Since the existence of the occipitofrontal fascicle (OFF) in humans has remained controversial, we utilized diffusion tensor imaging (DT-MRI)-based segmentation and tractography to investigate its trajectory in vivo in the human. We found that the OFF is distinct from the subcallosal fasciculus or Muratoff's bundle (MB) and extends from the dorsal and medial parts of the occipital lobe as well as the dorsal, medial and inferior parietal lobules to the dorsal and medial part of the prefrontal and premotor regions. In most of its course, it remains parallel to the corpus callosum, the caudate nucleus and the lateral ventricle. In the coronal plane, the OFF is discerned in the core of the white matter medial to the corona radiata and the superior longitudinal fascicle 11 (SLIT 11) and lateral to MB and the corpus callosum. The volumetric measurements of the stem portion of the OFF indicate that the OFF is smaller than the SLIT 11 and the cingulum bundle. Since DT-MRI allows the visualization of OFF fibers leading to the projection areas but not to the origin or termination of these fibers, this has been extrapolated from the experimental data in non-human primates. The OFF may have a role in visual spatial processing along with SLF II. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Radiol Serv,Ctr Morphometr Anal, Boston, MA 02129 USA. Boston Univ, Dept Anat & Neurobiol, Sch Med, Boston, MA 02215 USA. RP Makris, N (reprint author), Massachusetts Gen Hosp, Ctr Morphometr Anal, Bldg 149,13th St, Charlestown, MA 02129 USA. EM nikos@cma.mgh.harvard.edu RI Kennedy, David/H-3627-2012 FU NCCIH NIH HHS [P01 AT002048]; NINDS NIH HHS [R01 NS034189, NS34189] NR 49 TC 40 Z9 42 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2007 VL 37 IS 4 BP 1100 EP 1111 DI 10.1016/j.neuroimage.2007.05.042 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 214YF UT WOS:000249773600015 PM 17681797 ER PT J AU Miller, KL Smith, SM Jezzard, P Wiggins, GC Wiggins, CJ AF Miller, Karla L. Smith, Stephen M. Jezzard, Peter Wiggins, Graham C. Wiggins, Christopher J. TI Signal and noise characteristics of SSFPFMRI: A comparison with GRE at multiple field strengths SO NEUROIMAGE LA English DT Article ID STATE FREE PRECESSION; STEADY-STATE; PHYSIOLOGICAL NOISE; BALANCED SSFP; FMRI; BLOOD; TRUEFISP; MRI AB Recent work has proposed the use of steady-state free precession (SSFP) as an alternative to the conventional methods for obtaining functional MRI (FMRI) data. The contrast mechanism in SSFP is likely to be related to conventional FM RI signals, but the details of the signal changes may differ in important ways. Functional contrast in SSFP has been proposed to result from several different mechanisms, which are likely to contribute in varying degrees depending on the specific parameters used in the experiment. In particular, the signal dynamics are likely to differ depending on whether the sequence is configured to scan in the SSFP transition band or passband. This work describes experiments that explore the source of SSFP FMRI signal changes by comparing SSFP data to conventional gradient-recalled echo (GRE) data. Data were acquired at a range of magnetic field strengths and repetition times, for both transition band and passband methods. The signal properties of SSFP and GRE differ significantly, confirming a different source of functional contrast in SSFP. In addition, the temporal noise properties are significantly different, with important implications for SSFP FMRI sequence optimisation. (c) 2007 Elsevier Inc. All rights reserved. C1 John Radcliffe Hosp, FMRIB Ctr, Oxford OX3 9DU, England. Massachusetts Gen Hosp, AA Martinos Ctr, Charlestown, MA USA. RP Miller, KL (reprint author), John Radcliffe Hosp, FMRIB Ctr, Oxford OX3 9DU, England. EM karla@fmrib.ox.ac.uk OI Miller, Karla/0000-0002-2511-3189; Jezzard, Peter/0000-0001-7912-2251; Smith, Stephen/0000-0001-8166-069X NR 17 TC 30 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2007 VL 37 IS 4 BP 1227 EP 1236 DI 10.1016/j.neuroimage.2007.06.024 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 214YF UT WOS:000249773600027 PM 17706432 ER PT J AU Chen, WL Song, BB Lao, L Perez, OA Kim, W Marvizon, JCG AF Chen, Wenling Song, Bingbing Lao, Lijun Perez, Orlando A. Kim, Woojae Marvizon, Juan Carlos G. TI Comparing analgesia and mu-opioid receptor internalization produced by intrathecal enkephalin: Requirement for peptidase inhibition SO NEUROPHARMACOLOGY LA English DT Article DE aminopeptidase; dipeptidyl carboxypeptidase; EC.3.4.11.7; EC.3.4.15.1; EC.3.4.24.11; endomorphin; enkephalin; delta opioid receptor; dorsal horn; intrathecal; Mu opioid receptor; neutral endopeptidase; peptidase inhibitors; tail-flick test ID RAT SPINAL-CORD; DORSAL-HORN NEURONS; NOXIOUS MECHANICAL STIMULI; MEDIAL PREOPTIC NUCLEUS; D-ASPARTATE RECEPTORS; SUBSTANCE-P; DEGRADING ENZYMES; PRIMARY AFFERENTS; CHRONIC CATHETERIZATION; ELECTRICAL-STIMULATION AB Opioid receptors in the spinal cord produce strong analgesia, but the mechanisms controlling their activation by endogenous opioids remain unclear. We have previously shown in spinal cord slices that peptidases preclude p-opioid receptor (MOR) internalization by opioids. Our present goals were to investigate whether enkephalin-induced analgesia is, also precluded by peptidases, and whether it is mediated by MORs or delta-opioid receptors (DORs). Tail-flick analgesia and MOR internalization were measured in rats injected intrathecally with Leu-enkephalin and peptidase inhibitors. Without peptidase inhibitors, Leu-enkephalin produced neither analgesia nor MOR internalization at doses up to 100 nmol. whereas with peptidase inhibitors it produced analgesia at 0.3 nmol and MOR internalization at I nmol. Leu-enkephalin was 10 times more potent to produce analgesia than to produce MOR internalization, suggesting that DORs were involved. Selective MOR or DOR antagonists completely blocked the analgesia elicited by 0.3 nmol Leu-enkephalin (a dose that produced little MOR internalization), indicating that it involved these two receptors, possibly by an additive or synergistic interaction. The selective MOR agonist endomorphin-2 produced analgesia even in the presence of a DOR antagonist, but at doses substantially higher than Leu-enkephalin. Unlike Leu-enkephalin, endomorphin-2 had the same potencies to induce analgesia and MOR internalization. We concluded that low doses of enkephalins produce analgesia by activating both MORs and DORs. Analgesia can also be produced exclusively by MORs at higher agonist doses. Since peptidases prevent the activation of spinal opioid receptors by enkephalins, the coincident release of opioids and endogenous peptidase inhibitors may be required for analgesia. (c) 2007 Elsevier Ltd. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis,Digest Dis Res Ctr, Los Angeles, CA 90073 USA. RP Marvizon, JCG (reprint author), VA Greater Los Angeles Healthcare Syst, Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM marvizon@ucla.edu RI Chen, Wenling/A-4490-2012 FU NIDA NIH HHS [R01 DA012609-07, R01 DA012609, R01 DA012609-08] NR 73 TC 21 Z9 23 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD OCT PY 2007 VL 53 IS 5 BP 664 EP 676 DI 10.1016/j.neurophann.2007.07.010 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 228PD UT WOS:000250741000010 PM 17845806 ER PT J AU Sim, ME Lyoo, IK Streeter, CC Covell, J Sarid-Segal, O Ciraulo, DA Kim, MJ Kaufman, MJ Yurgelun-Todd, DA Renshaw, PF AF Sim, Minyoung E. Lyoo, In Kyoon Streeter, Chris C. Covell, Julie Sarid-Segal, Ofra Ciraulo, Domenic A. Kim, Minue J. Kaufman, Marc J. Yurgelun-Todd, Deborah A. Renshaw, Perry F. TI Cerebellar gray matter volume correlates with duration of cocaine use in cocaine-dependent subjects SO NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 12-17, 2004 CL San Juan, PR SP Coll Problems Drug Dependence DE cocaine; cerebellum; optimized voxel-based morphometry ID ORBITOFRONTAL CORTEX; ALCOHOL DEPENDENCE; BRAIN CHANGES; ABUSERS; ADDICTION; MRI; DYSFUNCTION; METABOLISM; DEFICITS; MORPHOMETRY AB This study was conducted to explore differences in gray and white matter volume between cocaine-dependent and healthy comparison subjects using optimized voxel-based morphometry (VBM). Brain magnetic resonance imaging (MRI) and neuropsychological function tests were performed for 40 cocaine-dependent subjects (41.4 +/-6.9 years, 27 men) and 41 healthy age- and sex-matched comparison subjects (38. +/-78.8 years, 26 men). Optimally normalized whole brain MR images were segmented, modulated, smoothed, and compared between groups with statistical parametric mapping. The cocaine-dependent group had lower gray matter volumes in bilateral premotor cortex (Brodmann area (BA) 6, 8; 16.6%), right orbitofrontal cortex (BA 10, 15.1%), bilateral temporal cortex (BA 20, 38; 15.9%), left thalamus (12.6%), and bilateral cerebellum (13.4%) as well as lower right cerebellar white matter volume (10.0%) relative to the comparison group at a corrected p < 0.05 for multiple comparisons. Duration of cocaine use negatively correlated with right and left cerebellar gray matter volumes (r = -0.37, r = -0.39, respectively). In cocaine-dependent subjects, lower cerebellar hemispheric gray and white matter volumes were correlated with deficits in executive function and decreased motor performance. This study reports that cocaine-dependent subjects have lower gray matter volumes in cerebellar hemispheres as well as in frontal, temporal cortex, and thalamus. These findings are the first to suggest that the cerebellum may be vulnerable to cocaine-associated brain volume changes, and that cerebellar deficits may contribute to neuropsychological deficits and motor dysfunction frequently observed in cocaine-dependent subjects. C1 Seoul Natl Univ, Coll Med, Dept Psychiat, Seoul 110744, South Korea. Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr,Dept Psychiat, Belmont, MA 02178 USA. Boston Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Lyoo, IK (reprint author), Seoul Natl Univ, Coll Med, Dept Psychiat, 28 Yongon Dong, Seoul 110744, South Korea. EM inkylyoo@yahoo.com OI Ciraulo, Domenic/0000-0001-7706-8765; Kim, Justin/0000-0002-5886-8545 FU NIAAA NIH HHS [AA013727, K23AA13149]; NIDA NIH HHS [DA014674, DA017324, DA09448-09S1, DA15116, DA50038] NR 54 TC 93 Z9 95 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2007 VL 32 IS 10 BP 2229 EP 2237 DI 10.1038/sj.npp.1301346 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 211EB UT WOS:000249506000019 PM 17299505 ER PT J AU Aghi, MK Eskandar, EN Carter, BS Curry, WT Barker, FG AF Aghi, Manish K. Eskandar, Emad N. Carter, Bob S. Curry, William T., Jr. Barker, Fred G. TI Increased prevalence of obesity and obesity-related postoperative complications in male patients with meningiomas SO NEUROSURGERY LA English DT Article DE estrogen; male; meningioma; obesity; postoperative complications ID BODY-MASS INDEX; BREAST-CANCER; RISK-FACTORS; POSTMENOPAUSAL WOMEN; FAT MASS; EPIDEMIOLOGY; RECEPTORS; ESTROGEN; PROGESTERONE; ASSOCIATION AB OBJECTIVE: The female preponderance of meningiomas may reflect hormonal influ ences on meningioma growth. We hypothesized that because obesity affects male steroid hormone synthesis, male patients with meningiomas might exhibit a high obesity rate, which, in turn, might increase their frequency of postoperative complications. METHODS: We retrospectively reviewed male patients who underwent craniotomy for benign meningiomas at our institution between 2001 and 2005 (n = 32) and used male patients undergoing craniotomy for aneurysms (n = 32) or glioblastomas (n = 32) from 2001 to 2005 as control subjects. Body mass index (BMI greater than 30 kg/m(2) was considered obese. RESULTS: Male patients with meningiomas had a higher average BMI (30.2 kg/m(2)) 9 than male patients with aneurysms (BMI = 27.5 kg/m(2)) or gliomas (BMI = 25.9 kg/m(2)) (P = 0.04). The obesity rate in men with meningiomas (47%) exceeded that in men with aneurysms (19%) or gliomas (3%) (P = 0.2). The median age-normalized BMI percentile was greater in men with meningiomas (67th percentile) than in men with aneurysms (49th percentile) or gliomas (52nd percentile) (P = 0.02). Deep vein thrombosis/pulmonary embolus was more common in men with meningiomas (19%) than in men with aneurysms (0%) or gliomas (3%) (P = 0.002). Wound infections were more common in men with meningiomas (6%) than in men with aneurysms (3%) or gliomas (0%) (P = 0.2). The 53% of obese patients with meningiomas who were readmitted with postoperative complications exceeded the 18% of nonobese patients with meningiomas who were readmitted (P = 0.03); complications included deep vein thrombosis and pulmonary embolus (27 and 12%, respectively, in obese and nonobese patients with meningiomas) and postoperative fever (53 and 35%, respectively, in obese and nonobese patients with meningiomas). CONCLUSION: We found that many men with meningiomas are obese, suggesting a hormonal influence on meningiomas in men as well as women. Our results also underscore the high risk of postoperative complications in obese male patients with meningiomas. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. RP Aghi, MK (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, White Bldg Room 502,55 Fruit St, Boston, MA 02114 USA. EM maghi@partners.org NR 39 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD OCT PY 2007 VL 61 IS 4 BP 754 EP 760 DI 10.1227/01.NEU.0000280062.82973.C8 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 226GZ UT WOS:000250577400015 PM 17986936 ER PT J AU Slotkin, JR Lu, Y Wood, KB AF Slotkin, Jonathan R. Lu, Yi Wood, Kirkham B. TI Thoracolumbar spinal trauma in children SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID CORD-INJURY; RADIOGRAPHIC ABNORMALITIES; HOSPITAL ADMISSIONS; THORACIC SCIWORA; CERVICAL-SPINE; FRACTURE; ADOLESCENTS; PATHOGENESIS AB Pediatric thoracolumbar spinal trauma is a relatively rare event. It is important to understand the unique mechanical, diagnostic, and management considerations of this patient population. Inadequate recognition of thoracolumbar spinal injuries or suboptimal management may lead to less than ideal clinical outcomes in a population of patients who otherwise would have had great potential for recovery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Childrens Hosp, Sch Med,Dept Neurosurg, Boston, MA 02115 USA. RP Wood, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM kbwood@partners.org NR 39 TC 8 Z9 8 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 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD OCT PY 2007 VL 18 IS 4 BP 621 EP + DI 10.1016/j.nec.2007.07.003 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 237HO UT WOS:000251365000005 PM 17991587 ER PT J AU Drevets, WC Thase, ME Moses-Kolko, EL Price, J Frank, E Kupfer, DJ Mathis, C AF Drevets, Wayne C. Thase, Michael E. Moses-Kolko, Eydie L. Price, Julie Frank, Ellen Kupfer, David J. Mathis, Chester TI Serotonin-1A receptor imaging in recurrent depression: replication and literature review SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Workshop on After Bench to Bedside - Impact on Clinical Outcome CY 2007 CL La Jolla, CA ID POSITRON-EMISSION-TOMOGRAPHY; MESSENGER-RNA EXPRESSION; ANTIDEPRESSANT DRUG-TREATMENT; 5-HT1A RECEPTOR; MAJOR DEPRESSION; HUMAN-BRAIN; MINERALOCORTICOID RECEPTOR; AUTORADIOGRAPHIC ANALYSES; BIPOLAR DEPRESSION; DORSAL HIPPOCAMPUS AB Introduction: Serotonin-1A receptor (5-HT(1A)R) function appears to be decreased in major depressive disorder (MDD) based on physiological responses to 5-HT(1A)R agonists in vivo and to 5-HT(1A)R binding in brain tissues postmortem or antemortem. We have previously assessed 5-HT(1A)R binding potential (BP) in depression using positron emission tomography (PET) and [carbonyl-(11)C]WAY-100635, and we have demonstrated reduced 5-HT(1A)R BP in the mesiotemporal cortex (MTC) and raphe in depressives with primary recurrent familial mood disorders (n=12) versus controls (n=8) [Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C. PET imaging of serotonin I A receptor binding in depression. Biol Psychiatry 1999;46(10):1375-87]. These findings were replicated by some, but not other, studies performed in depressed samples that were more generally selected using criteria for MDD. In the current study, we attempted to replicate our previous findings in an independent sample of subjects selected according to the criteria for primary recurrent depression applied in our prior study. Methods: Using PET and [carbonyl-(11)C]WAY-100635, 5-HT(1A)R BP was assessed in 16 depressed subjects and 8 healthy controls. Results: Mean 5-HT(1A)R BP was reduced by 26% in the MTC (P<.005) and by 43% in the raphe (P<.001) in depressives versus controls. Conclusions: These data replicate our original findings, which showed that BP was reduced by 27% in the MTC (P<.025) and by 42% in the raphe (P<.02) in depression. The magnitudes of these reductions in 5-HT(1A)R binding were similar to those found postmortem in 5-HT(1A)R mRNA concentrations in the hippocampus in MDD [Lopez JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547-73] and in 5-HT(1A)R-binding capacity in the raphe in depressed suicide victims [Arango V, Underwood MD, Boldrini M, Tamir H, Kassir SA, Hsiung S, Chen JJ, Mann JJ. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 2001-,25(6):892-903]. There exists disagreement within the literature, however, regarding the presence and direction of 5-HT(1A)R-binding abnormalities in depression, which may be explained in some cases by differences in anatomical location (e.g., [Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G. Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression -postmortem evidence for decreased serotonin activity. J Neurosci 1998;18(18):7394-401]) and in other cases by pathophysiological heterogeneity within MDD (e.g., some depressives hypersecrete cortisol, which would be expected to down-regulate 5-HT(1A)R expression [Lopez JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547-73]). Antidepressant drug treatment does not alter these abnormalities in 5-HTIAR binding [Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, Gunn RN, Grasby PM, Cowen PJ. Brain serotonin(1A) receptor binding measured by positron emission tomography with [(11)C]WAY-1 00635: effects of depression and antidepressant treatment. Arch Gen Psychiatry 2000;57(2):174-80; Moses-Kolko EL, Price JC, Thase ME, Meltzer CC, Kupfer DJ, Mathis CA, Bogers WD, Berman SR, Houck PR, Schneider TN, Drevets WC. Measurement of 5-HT(1A) receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [(11)C]WAY-100635. Synapse 2007;61(7):523-30] but may compensate for blunted 5-HT(1A)R function by increasing post-synaptic 5-HT(1A)R transmission [Chaput Y, de Montigny C, Blier P. Presynaptic and postsynaptic modifications of the serotonin system by long-terin administration of antidepressant treatments. An in vivo electrophysiologic study in the rat. Neuropsychopharmacology 1991;5(4):219-29]. C 2007 Elsevier Inc. All rights reserved. C1 MINH Mol Imaging Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 19213 USA. Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 19213 USA. Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. RP Drevets, WC (reprint author), NIH NIMH DIRP, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. EM drevetsw@mail.nih.gov FU Intramural NIH HHS [Z01 MH002788-06]; NIMH NIH HHS [K23 MH064561] NR 109 TC 212 Z9 221 U1 2 U2 31 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD OCT PY 2007 VL 34 IS 7 BP 865 EP 877 DI 10.1016/j.nuemedbio.2007.06.008 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 222WI UT WOS:000250328100016 PM 17921037 ER PT J AU Amicarelli, G Shehi, E Makrigiorgos, GM Adlerstein, D AF Amicarelli, Giulia Shehi, Erlet Makrigiorgos, G. Mike Adlerstein, Daniel TI FLAG assay as a novel method for real-time signal generation during PCR: application to detection and genotyping of KRAS codon 12 mutations SO NUCLEIC ACIDS RESEARCH LA English DT Article ID K-RAS MUTATIONS; FACTOR-V-LEIDEN; ALLELE-SPECIFIC AMPLIFICATION; DNA DIAGNOSTIC METHOD; CELL LUNG-CANCER; RESTRICTION-ENDONUCLEASE; MOLECULAR BEACONS; OLIGONUCLEOTIDE PROBES; HYBRIDIZATION PROBES; POINT MUTATIONS AB Real-time signal generation methods for detection and characterization of low-abundance mutations in genomic DNA are powerful tools for cancer diagnosis and prognosis. Mutations in codon 12 of the oncogene KRAS, for example, are frequently found in several types of human cancers. We have developed a novel real-time PCR technology, FLAG (FLuorescent Amplicon Generation) and adapted it for simultaneously (i) amplifying mutated codon 12 KRAS sequences, (ii) monitoring in real-time the amplification and (iii) genotyping the exact nucleotide alteration. FLAG utilizes the exceptionally thermostable endonuclease PspGI for real-time signal generation by cleavage of quenched fluorophores from the 5-end of the PCR products and, concurrently, for selecting KRAS mutations over wild type. By including peptide-nucleic-acid probes in the reaction, simultaneous genotyping is achieved that circumvents the requirement for sequencing. FLAG enables high-throughput, closed-tube KRAS mutation detection down to 0.1 mutant-to-wild type. The assay was validated on model systems and compared with allele-specific PCR sequencing for screening 27 cancer specimens. Diverse applications of FLAG for real-time PCR or genotyping applications in cancer, virology or infectious diseases are envisioned. C1 DiaSorin SpA, I-13040 Saluggia, Italy. Harvard Univ, Sch Med, Dana Faber Brigham & Womens Canc Ctr, Boston, MA USA. RP Adlerstein, D (reprint author), DiaSorin SpA, Via Crescentino Snc, I-13040 Saluggia, Italy. EM daniel.adlerstein@diasorin.it FU NCI NIH HHS [CA111994-01, CA115439-01, R21 CA111994, R21 CA115439, R33 CA111994] NR 49 TC 32 Z9 34 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2007 VL 35 IS 19 AR e131 DI 10.1093/nar/gkm809 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229TJ UT WOS:000250827000037 PM 17932053 ER PT J AU Ham, M Horton, K Kaunitz, J AF Ham, Maggie Horton, Kelli Kaunitz, Jonathan TI Fistuloclysis: Case report and literature review SO NUTRITION IN CLINICAL PRACTICE LA English DT Article ID TOTAL PARENTERAL-NUTRITION; CONTINUOUS ENTERAL NUTRITION; C-REACTIVE PROTEIN; ENTEROCUTANEOUS FISTULA; GASTROINTESTINAL FISTULAS; SOMATOSTATIN ANALOG; ELEMENTAL DIET; SERUM-ALBUMIN; SMALL-BOWEL; MANAGEMENT AB Enterocutaneous fistulae are a common postoperative entity, causing serious complications such as sepsis, malnutrition, and electrolyte and fluid abnormalities. Because sepsis coupled with malnutrition is the leading cause of death in these patients, it is especially important to provide nutrition support. Although parenteral nutrition (PN) is widely used in these patients, it is not without risks, because PN is known to cause liver dysfunction, among other problems. We report a case in which a male patient with an enterocutaneous fistula, having experienced increased liver enzymes receiving PN, began receiving enteral nutrition (EN) via a feeding tube placed in the fistula. Known as fistuloclysis, this method provided adequate nutrition and improved his serum albumin and prealbumin levels, body weight, and liver function tests. Upon stabilization of his nutrition status, he was able to undergo successful surgical repair of the enterocutaneous fistula. According to our experience and that of others, we recommend that patients with high-output enterocutaneous fistulae be considered for EN via fistuloclysis after nutrition stabilization with PN; then the fistulae can be surgically repaired if not spontaneously healed. Use of EN via fistuloclysis, if used appropriately, avoids the complications of long-term PN and may promote faster fistula healing. C1 Univ Calif Los Angeles, David Geffen Sch Med, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Sch Med, Los Angeles, CA USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Kaunitz, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Sch Med, Dept Med, Bldg 114 Room 217E,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu NR 42 TC 7 Z9 7 U1 0 U2 2 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0884-5336 J9 NUTR CLIN PRACT JI Nutr. Clin. Pract. PD OCT PY 2007 VL 22 IS 5 BP 553 EP 557 DI 10.1177/0115426507022005553 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 218BU UT WOS:000249991800011 PM 17906279 ER PT J AU Iwasaki, H Akashi, K AF Iwasaki, H. Akashi, K. TI Hematopoietic developmental pathways: on cellular basis SO ONCOGENE LA English DT Review DE hematopoietic stem cell; lineage commitment; transcription factor; leukemic stem cell ID ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; COMMON LYMPHOID PROGENITORS; RECEPTOR TYROSINE KINASE; STEM-CELLS; BONE-MARROW; LONG-TERM; LINEAGE COMMITMENT; DENDRITIC CELLS; CORD-BLOOD AB To elucidate the molecular mechanisms underlying normal and malignant hematopoietic development, it is critical to identify developmental intermediates for each lineage downstream of hematopoietic stem cells. Recent advances in prospective isolation of hematopoietic stem and progenitor cells, and effficient xenogeneic transplantation systems have provided a detailed developmental map in both mouse and human hematopoiesis, demonstrating that surface phenotypes of mouse stem - progenitor cells and their human counterparts are considerably different. Here, we summarize the phenotype and functional properties and their differences of hematopoietic stem and progenitor cell populations between mouse and human. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. RP Akashi, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM Koichi_akashi@dfci.harvard.edu NR 100 TC 44 Z9 47 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 2007 VL 26 IS 47 BP 6687 EP 6696 DI 10.1038/sj.onc.1210754 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 220HE UT WOS:000250147000002 PM 17934478 ER PT J AU O'Neil, J Look, AT AF O'Neil, J. Look, A. T. TI Mechanisms of transcription factor deregulation in lymphoid cell transformation SO ONCOGENE LA English DT Review DE TAL1; NOTCH; PAX5; MLL; E2A; TEL-AML1 ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DNA-BINDING DOMAIN; C-MYC ONCOGENE; SITE-SPECIFIC DELETIONS; ZINC-FINGER PROTEIN; LOOP-HELIX PROTEIN; T-CELL; TRANSGENIC MICE; CHROMOSOMAL TRANSLOCATIONS; BURKITT-LYMPHOMA AB The most frequent targets of genetic alterations in human lymphoid leukemias are transcription factor genes with essential functions in blood cell development. TAL1, LYL1, HOX11 and other transcription factors essential for normal hematopoiesis are often misexpressed in the thymus in T- cell acute lymphoblastic leukemia ( T- ALL), leading to differentiation arrest and cell transformation. Recent advances in the ability to assess DNA copy number have led to the discovery that the MYB transcription factor oncogene is tandemly duplicated in T- ALL. The NOTCH1 gene, which is essential for key embryonic cell-fate decisions in multicellular organisms, was found to be activated by mutation in a large percentage of T- ALL patients. The gene encoding the FBW7 protein ubiquitin ligase, which regulates the turnover of the intracellular form of NOTCH ( ICN), is also mutated in T- ALL, resulting in stabilization of the ICN and activation of the NOTCH signaling pathway. In mature B- lineage ALL and Burkitt lymphoma, the MYC transcription factor oncogene is overexpressed due to translocation into the IG locus. PAX5, a transcription factor essential for B- lineage commitment, is inactivated in 32% of cases of B- progenitor ALL. Translocations resulting in oncogenic fusion transcription factors also occur frequently in this form of ALL. The most frequent transcription factor chimeric fusion, TEL- AML1, is an initiating event in B- progenitor ALL that acts by repressing transcription. Therefore, deregulated transcription and its consequent effects on key developmental pathways play a major role in the molecular pathogenesis of lymphoid malignancy. Once the full complement of cooperating mutations in transformed B- and T- progenitor cells is known, and the deregulated downstream pathways have been elucidated, it will be possible to identify vulnerable components and to target them with small- molecule inhibitors. C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM Thomas_Look@dfci.harvard.edu FU NCI NIH HHS [CA109901] NR 170 TC 85 Z9 85 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 2007 VL 26 IS 47 BP 6838 EP 6849 DI 10.1038/sj.onc.1210766 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 220HE UT WOS:000250147000014 PM 17934490 ER PT J AU Nezam, SMRM Vakoc, BJ Desjardins, AE Tearney, GJ Bouma, BE AF Nezam, S. M. R. Motaghian Vakoc, B. J. Desjardins, A. E. Tearney, G. J. Bouma, B. E. TI Increased ranging depth in optical frequency domain imaging by frequency encoding SO OPTICS LETTERS LA English DT Article ID COHERENCE TOMOGRAPHY; INTERFEROMETRY; DEGENERACY; LASER AB A technique for increasing the ranging depth in optical frequency domain imaging utilizing frequency encoding is presented. Ranging depth is enhanced by using two interferometer reference arms with different path lengths and independent modulation frequencies (25 and 50 MHz). With this configuration, the sensitivity decreases by 6 dB over a depth range of 7 mm, approximately a threefold improvement over the conventional optical frequency domain imaging technique. We demonstrate that the reference arm frequency separation, tuning speed, center wavelength, and instantaneous coherence length determine the signal-tocross-talk ratio. (c) 2007 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Nezam, SMRM (reprint author), Harvard Univ, Sch Med, 55 Fruit St,BAR 718, Boston, MA 02114 USA. EM Motaghiannezam.Reza@mgh.harvard.edu FU NCI NIH HHS [R01 CA103769, R01 CA103769-04]; NHLBI NIH HHS [R01 HL076398, R01 HL076398-05] NR 13 TC 12 Z9 12 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD OCT 1 PY 2007 VL 32 IS 19 BP 2768 EP 2770 DI 10.1364/OL.32.002768 PG 3 WC Optics SC Optics GA 225EM UT WOS:000250499900001 PM 17909567 ER PT J AU Razansky, D Vinegoni, C Ntziachristos, V AF Razansky, Daniel Vinegoni, Claudio Ntziachristos, Vasilis TI Multispectral photoacoustic imaging of fluorochromes in small animals SO OPTICS LETTERS LA English DT Article ID ANGIOGENESIS; TOMOGRAPHY; BRAIN AB Fluorochromes have become essential reporter molecules in biological research. We show that the depth-resolved distribution of fluorochromes in small animals can be imaged with 25 fmol sensitivity and 150 Am spatial resolution by means of multispectral photoacoustic imaging. The major advantage of the multispectral approach is the sensitive differentiation of chromophores and fluorochromes of interest based on self-reference measurements, as evidenced in this study by resolving a commonly used fluorochrome (Alexa Fluor 750) in mouse. The suggested method is well suited for enhancing visualization of functional and molecular information in vivo and longitudinally. (c) 2007 Optical Society of America. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Ntziachristos, V (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM vasilis@helix.mgh.harvard.edu OI Razansky, Daniel/0000-0001-8676-0964 NR 11 TC 128 Z9 128 U1 0 U2 22 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD OCT 1 PY 2007 VL 32 IS 19 BP 2891 EP 2893 DI 10.1364/OL.32.002891 PG 3 WC Optics SC Optics GA 225EM UT WOS:000250499900042 PM 17909608 ER PT J AU Asefzadeh, B Cavallerano, AA Fisch, BM AF Asefzadeh, Baharak Cavallerano, Anthony A. Fisch, Barry M. TI Racial differences in macular thickness in healthy eyes SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE macular thickness; optical coherence tomography; retinal thickness; race ID OPTICAL COHERENCE TOMOGRAPHY; NERVE-FIBER LAYER; SCANNING LASER POLARIMETRY; OPEN-ANGLE GLAUCOMA; DIABETIC-RETINOPATHY; BLACKS; WHITES; EDEMA; OCT AB Purpose. The relationship between race and macular thickness remains unknown. This relationship may be important for early and accurate diagnosis of macular disease and glaucoma, and may also provide insight into disease mechanisms. In this study, we compared macular thickness in healthy eyes of black and white subjects using optical coherence tomography (Stratus OCT). Methods. This study used a matched, cross-sectional design. Subjects underwent OCT macular thickness map scanning in each eye, four-field, 45-degree digital retinal imaging in each eye, and blood pressure measurement. Retinal images were evaluated for absence of posterior pole disorders, including macular and optic nerve disease. Retinal thickness was evaluated in the central fovea, and in rings placed at 1, 3, and 6 mm from fixation. Results. Compared with whites (n = 7), blacks (n = 7) had significantly thinner total foveal thickness (TFT, retinal thickness in the central 1 mm diameter area; OD: p < 0.03; OS: p < 0.02; OU average: p < 0.02), and thinner total macular thickness (TMT, retinal thickness in 6mm diameter area excluding central foveal thickness; OS: p < 0.02; OU average: p < 0.03). There was a trend for central foveal thickness (retinal thickness at fixation) to be thinner in blacks than whites (OD: p = 0.12; OS: p = 0.08). There was no significant difference in macular thickness between right and left eyes. Conclusions. Retinal thickness as measured by Stratus OCT in the fovea and macula is significantly thinner in blacks compared with age-matched whites. Larger multiracial prospective studies are needed to confirm these results and to evaluate the need for race-specific normative values. C1 VA Boston Healthcare Syst, Jamaica Plain, MA USA. New England Coll Optometry, Boston, MA USA. RP Asefzadeh, B (reprint author), VA Boston Ocular TeleHlth Ctr, VA Boston Hlth Care Syst, Eye Clin, 8th Floor,150 S Huntington Ave, Boston, MA 02130 USA. EM Baharak.Asefzadeh@va.gov NR 25 TC 41 Z9 41 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD OCT PY 2007 VL 84 IS 10 BP 941 EP 945 PG 5 WC Ophthalmology SC Ophthalmology GA 226ON UT WOS:000250598500003 PM 18049358 ER PT J AU Reiber, GE Raugi, GJ Rowberg, D AF Reiber, Gayle E. Raugi, Gregory J. Rowberg, Donald TI The process of implementing a rural VA wound cave program for diabetic foot ulcer patients SO OSTOMY WOUND MANAGEMENT LA English DT Article DE diabetes; foot ulcer; systems of care; electronic medical records; wound care ID MANAGEMENT; TRIAL AB Delivering and documenting evidence-based treatment to all Department of Veterans Affairs (VA) foot ulcer patients has wide appeal. However, primary and secondary care medical centers where 52% of these patients receive care are at a disadvantage given the frequent absence of trained specialists to manage diabetic foot ulcers. A retrospective review of diabetic foot ulcer patient records and a provider survey were conducted to document the foot ulcer problem and to assess practitioner needs. Results showed of the 125 persons with foot ulcers identified through administrative data, only, 21% of diabetic foot patients were correctly coded. Chronic Care and Microsystem models were used to prepare a tailored intervention in a VA primary care medical center. The site Principal Investigators, a multidisciplinary site wound care team, and study investigators jointly implemented a diabetic foot ulcer program. Intervention components include wound care team education and training, standardized good wound care practices based on strong scientific evidence, and a wound care template embedded in the electronic medical record to facilitate data collection, clinical decision making, patient ordering, and coding. A strategy for delivering offloading pressure devices, regular case management support, and 24/7 emergency assistance also was developed. It took 9 months to implement the model. Patients were enrolled and followed for 1 year Process and outcome evaluations are on-going. C1 VA Puget Sound, Hlth Care Syst, Seattle, WA 98101 USA. Univ Washington, Epidemiol & Hlth Serv, Seattle, WA 98195 USA. VA Puget Sound, Hlth Care Syst, Dermatol Sect, Seattle, WA 98101 USA. Univ Washington, Seattle, WA 98195 USA. Walla Walla VA Med Ctr, Walla Walla, WA USA. RP Reiber, GE (reprint author), VA Puget Sound, Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM greiber@u.wash-ington.edu NR 15 TC 5 Z9 5 U1 1 U2 1 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 0889-5899 J9 OSTOMY WOUND MANAG JI Ostomy Wound Manag. PD OCT PY 2007 VL 53 IS 10 BP 60 EP 66 PG 7 WC Surgery SC Surgery GA 225TX UT WOS:000250541700010 PM 17978416 ER PT J AU Franco, RA Andrus, JG AF Franco, Ramon A. Andrus, Jennifer G. TI Common diagnoses and treatments in professional voice users SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Review ID VOCAL FOLD PARESIS; PULSED DYE-LASER; MUSCLE TENSION DYSPHONIA; LARYNGOPHARYNGEAL REFLUX; TRANSNASAL ESOPHAGOSCOPY; SULCUS VOCALIS; FEMALE VOICE; GASTROESOPHAGEAL-REFLUX; FUNCTIONAL DYSPHONIA; LARYNGEAL CARCINOMA AB Common problems among all patients with vocal difficulties seen by the laryngologist also are common among professional voice users. These include laryngopharyngeal reflux, muscle tension dysphonia, fibrovascular vocal fold lesions (eg, nodules and polyps), cysts, vocal fold scarring, and changes in vocal fold mobility. Microvascular lesions and their associated sequelae of vocal fold hemorrhage and laryngitis due to voice overuse are more common among professional voice users. Much more common among professional voice users is the negative impact that voice problems have on their ability to work, on their overall sense of well-being, and sometimes on their very sense of self. In diagnosing voice disorders in professional voice users, clinicians must possess and clearly convey an understanding of this important truism, which will facilitate trust, confidence, and the opportunity to treat the patient. This article reviews the diagnosis and treatment options for common problems among professional voice users, emphasizing the importance of gaining insight into the "whole" patient and of developing individualized management plans. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Div Laryngol, Boston, MA 02114 USA. RP Franco, RA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Div Laryngol, 243 Charles St, Boston, MA 02114 USA. EM ramon.franco@meei.harvard.edu NR 102 TC 24 Z9 26 U1 1 U2 19 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 2007 VL 40 IS 5 BP 1025 EP + DI 10.1016/j.otc.2007.05.008 PG 38 WC Otorhinolaryngology SC Otorhinolaryngology GA 216DO UT WOS:000249858500008 PM 17765694 ER PT J AU Barker, FG AF Barker, Fred G., II TI Quality of life and individual treatment choice in trigeminal neuralgia SO PAIN LA English DT Editorial Material ID MAGNETIC-RESONANCE ANGIOGRAPHY; MICROVASCULAR DECOMPRESSION; NEUROVASCULAR COMPRESSION; CANCER-PATIENTS; UTILITY C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 19 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT PY 2007 VL 131 IS 3 BP 234 EP 236 DI 10.1016/j.pain.2007.07.005 PG 3 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 220SU UT WOS:000250178400002 PM 17768008 ER PT J AU Ballantyne, JC LaForge, KS AF Ballantyne, Jane C. LaForge, K. Steven TI Opioid dependence and addiction during opioid treatment of chronic pain (vol 129, pg 235, 2007) SO PAIN LA English DT Correction AB Throughout the long history of opiold drug use by humans, it has been known that opioids are powerful analgesics, but they can cause addiction. It has also been observed, and is now substantiated by multiple reports and studies, that during opioid treatment of severe and short-term pain, addiction arises only rarely. However, when opioids are extended to patients with chronic pain, and therapeutic opioid use is not confined to patients with severe and short-lived pain, compulsive opiold seeking and addiction arising directly from opioid treatment of pain become more visible. Although the epidemiological evidence base currently available is rudimentary, it appears that problematic opioid use arises in some fraction of opioid-treated chronic pain patients, and that problematic behaviors and addiction are problems that need to be addressed. Since the potentially devastating effects of addiction can substantially offset the benefits of opioid pain relief, it seems timely to reexamine addiction mechanisms and their relevance to the practice of long-term opioid treatment for pain. This article reviews the neurobiological and genetic basis of addiction, its terminology and diagnosis, the evidence on addiction rates during opioid treatment of chronic pain and the implications of biological mechanisms in formulating rational opioid treatment regimes. C1 Massachusetts Gen Hosp Pain Ctr, Div Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Helsinki, Finnish Genome Ctr, Helsinki, Finland. RP Ballantyne, JC (reprint author), Massachusetts Gen Hosp Pain Ctr, Div Pain Med, 15 Parkman St,WACC 333, Boston, MA 02114 USA. EM jballantyne@partners.org NR 1 TC 1 Z9 1 U1 4 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT PY 2007 VL 131 IS 3 BP 350 EP 350 DI 10.1016/j.pain.2007.07.021 PG 1 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 220SU UT WOS:000250178400019 ER PT J AU Wiedemer, NL Harden, PS Arndt, IO Gallagher, RM AF Wiedemer, Nancy L. Harden, Paul S. Arndt, Isabelle O. Gallagher, Rollin M. TI The Opioid Renewal Clinic: A primary care, managed approach to opioid therapy in chronic pain patients at risk for substance abuse SO PAIN MEDICINE LA English DT Review DE opioids; primary care; chronic noncancer pain; substance abuse; pharmacy costs; pain medicine ID CHRONIC NONMALIGNANT PAIN; DRUG-ABUSE; BACK-PAIN; MEDICINE; DISORDERS; ADDICTION; COMMUNITY; INHIBITORS; CHALLENGE; EFFICACY AB Objective: To measure the impact of a structured opioid renewal program for chronic pain run by a nurse practitioner (NP) and clinical pharmacist in a primary care setting. Patients and Settings: Patients with chronic noncancer pain managed with opioid therapy in a primary care clinic staffed by 19 providers serving 50,000 patients at an urban academic Veterans hospital. Design: Naturalistic prospective outcome study. Intervention: Based on published opioid prescribing guidelines and focus groups with primary care providers (PCPs), a structured program, the Opioid Renewal Clinic (ORC), was designed to support PCPs managing patients with chronic noncancer pain requiring opioids. After training in the use of opioid treatment agreements (OTAs) and random urine drug testing (UDT), PCPs worked with a pharmacist-run prescription management clinic supported by an onsite pain NP who was backed by a multi-specialty Pain Team. After 2 years, the program was evaluated for its impact on PCP practice and satisfaction, patient adherence, and pharmacy cost. Results: A total of 335 patients were referred to the ORC. Of the 171 (51%) with documented aberrant behaviors, 77 (45%) adhered to the OTA and resolved their aberrant behaviors, 65 (38%) self-discharged, 22 (13%) were referred for addiction treatment, and seven (4%) with consistently negative UDT were weaned from opioids. The 164 (49%) who were referred for complexity including history of substance abuse or need for opioid rotation or titration, with no documented aberrant drug-related behaviors, continued to adhere to the OTA. Use of UDT and OTAs by PCPs increased. Significant pharmacy cost savings were demonstrated. Conclusion: An NP/clinical pharmacist-run clinic, supported by a multi-specialty team, can successfully support a primary care practice in managing opioids in complex chronic pain patients. C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Wiedemer, NL (reprint author), Philadelphia VA Med Ctr, 118, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM nancy.wiedemer@med.va.gov NR 59 TC 75 Z9 76 U1 1 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD OCT PY 2007 VL 8 IS 7 BP 573 EP 584 DI 10.1111/j.1526-4637.2006.00254.x PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 215RN UT WOS:000249826800006 PM 17883742 ER PT J AU Jamison, RN Fanciullo, GJ Baird, JC AF Jamison, Robert N. Fanciullo, Gilbert J. Baird, John C. TI "Computers in the future may weigh less than 1.5 tons." - Popular Mechanics, 1949 SO PAIN MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Jamison, RN (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. OI Jamison, Robert/0000-0003-1768-0906 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD OCT PY 2007 VL 8 SU 3 BP S83 EP S84 DI 10.1111/j.1526-4637.2007.00371.x PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 211HA UT WOS:000249513700001 ER PT J AU Jasser, SA Garvin, JH Wiedemer, N Roche, D Gallagher, RM AF Jasser, Samar A. Garvin, Jennifer H. Wiedemer, Nancy Roche, Dominic Gallagher, Rollin M. TI Information technology in mental health research: Impediments and implications in one chronic pain study population SO PAIN MEDICINE LA English DT Article DE coding; IT; schizophrenia; chronic pain ID ADMINISTRATIVE DATA; PREVALENCE; SCHIZOPHRENIA; DIAGNOSIS AB Objective. The Department of Veterans Affairs and Veterans' Administration hospitals began using the electronic medical record in 1994, streamlining provider-to-provider communication of vital clinical information, and simultaneously providing investigators access to vast amounts of clinical data for research purposes. Administrative and coded data, including symptoms and diagnoses as derived from chart content, are one of the most ready substrates for analysis of these massive databases to answer various research-related inquiries. We evaluated the capability of this type of coded data to accurately identify patients with schizophrenia from a group of 819 patients taking opioids for chronic pain in the primary care clinic of the Philadelphia Veterans' Administration Medical Center. Methods. Patients were identified for inclusion in this analysis by their sequential enrollment in an Opioid Renewal Clinic as referred by their primary care providers, as well as a nonreferred cohort of chronic pain patients maintained on opioids by their primary care providers (N = 819). The prevalence of schizophrenia obtained by coded diagnostic labeling by computerized chart review was compared with the prevalence of schizophrenia obtained by systematic independent manual chart review of all cases by a research psychiatrist. Results. Based purely on coded diagnostic labeling, the prevalence of schizophrenia in this population was 14%, nearly 14 times the estimated general population prevalence. However, manual independent chart review of the identified cases by a research psychiatrist (N = 119) resulted in the actual prevalence in this group to be estimated at 1.8%. None of the patients with three or less incidents of diagnostic labeling by code had schizophrenia. Of those with four or more incidents, 74% had schizophrenia. Conclusions. Better accuracy is obtained when cases of schizophrenia are identified by multiple coding incidents derived from longitudinal clinical encounters. These findings suggest that the extraction of up to three coding incidents for schizophrenia alone is not an accurate means of identifying this clinical population for research and epidemiological purposes. Further, when designing automated, information technology-based approaches to the identification of subjects for clinical research and extracting their data from electronic medical records using International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes, mental health diagnoses must be uniquely considered on a disease-by-disease basis. C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Pain Serv, Philadelphia, PA USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Anesthesiol, Philadelphia, PA 19104 USA. RP Jasser, SA (reprint author), Univ Penn, Sch Med, Dept Psychiat, 3535 Mrkt St,2nd Floor,2065, Philadelphia, PA 19104 USA. EM samarj@gmail.com NR 12 TC 1 Z9 1 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD OCT PY 2007 VL 8 SU 3 BP S176 EP S181 DI 10.1111/j.1526-4637.2007.00380.x PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 211HA UT WOS:000249513700011 ER PT J AU Eilegard, A Steineck, G Valdimarsdottir, U Kreicbergs, U AF Eilegard, Alexandra Steineck, Gunnar Valdimarsdottir, Unnur Kreicbergs, Ulrika TI To loose a sister or brother to cancer SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 Karolinska Hosp, S-10401 Stockholm, Sweden. Univ Iceland, MEB, Reykjavik, Iceland. Phyllis F Cantor Ctr, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT 1 PY 2007 VL 49 IS 4 BP 508 EP 508 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 205LU UT WOS:000249116100418 ER PT J AU Kreicbergs, U Lannen, P Onelov, E Wolfe, J AF Kreicbergs, Ulrika Lannen, Patricia Onelov, Erik Wolfe, Joanne TI Parental grief following the loss of a child to cancer SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 Karolinska Inst, Dana Farber Canc Inst, Stockholm, Sweden. Univ Bern, Bern, Switzerland. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT 1 PY 2007 VL 49 IS 4 BP 568 EP 569 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 205LU UT WOS:000249116100656 ER PT J AU Santucci, G Mack, JW AF Santucci, Gina Mack, Jennifer W. TI Common gastrointestinal symptoms in pediatric palliative care: Nausea, vomiting, constipation, anorexia, cachexia SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID OPIOID-RELATED CONSTIPATION; ASSESSMENT PG-SGA; QUALITY-OF-LIFE; ADVANCED CANCER; INTESTINAL-OBSTRUCTION; BOWEL OBSTRUCTION; ORAL NALOXONE; CHILDREN; MANAGEMENT; ABC AB Gastrointestinal symptoms are suffered commonly by children at the end of life. Diagnosis and management of these common symptoms include careful history and physical examination to assess for possible causes; treatment-pharmacologic and non-pharmacologic; and a discussion with patients and families of care goals. Aggressive management of these symptoms is essential to improving the quality of life for these children. C1 [Mack, Jennifer W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mack, Jennifer W.] Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. [Santucci, Gina] Childrens Hosp Philadelphia, Pediat Adv Care Team, Philadelphia, PA 19104 USA. RP Mack, JW (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jennifer_mack@dfci.harvard.edu NR 43 TC 12 Z9 12 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD OCT PY 2007 VL 54 IS 5 BP 673 EP + DI 10.1016/j.pcl.2007.06.001 PG 18 WC Pediatrics SC Pediatrics GA 249ET UT WOS:000252210800006 PM 17933617 ER PT J AU Ullrich, CK Mayer, OH AF Ullrich, Christina K. Mayer, Oscar H. TI Assessment and management of fatigue and dyspnea in pediatric palliative care SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID QUALITY-OF-LIFE; PLACEBO-CONTROLLED TRIAL; CANCER-RELATED FATIGUE; PATIENT-CONTROLLED METHYLPHENIDATE; DOUBLE-BLIND; NEBULIZED MORPHINE; EPOETIN-ALPHA; LUNG-CANCER; RECEIVING TREATMENT; HEMOGLOBIN LEVELS AB Fatigue is one of the most prevalent symptoms in patients with a life-threatening illness. Untreated, fatigue can impair quality of life and prohibit addressing practical needs, psychosocial and spiritual distress, and opportunities for growth and closure at life's end. To this end addressing fatigue is a crucial component of the provision of effective palliative care. Dyspnea is the sensation of breathlessness. The challenge in treating it, however, is that it can come from various different abnormalities so understanding the underlying disorder and the acute abnormality are critical. With that understanding several different treatments can be offered to treat the cause of the dyspnea or palliate the symptom itself. C1 [Ullrich, Christina K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ullrich, Christina K.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mayer, Oscar H.] Childrens Hosp Philadelphia, Div Pulm, Philadelphia, PA 19104 USA. [Mayer, Oscar H.] Childrens Hosp Philadelphia, Pediat Adv Care Team, Philadelphia, PA 19104 USA. RP Ullrich, CK (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM christina-ullrich@dfci.harvard.edu; mayero@email.chop.edu NR 68 TC 15 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD OCT PY 2007 VL 54 IS 5 BP 735 EP + DI 10.1016/j.pcl.2007.07.006 PG 23 WC Pediatrics SC Pediatrics GA 249ET UT WOS:000252210800009 PM 17933620 ER PT J AU Bismuth, E Laffel, L AF Bismuth, E. Laffel, L. TI Can we prevent diabetic ketoacidosis in children? SO PEDIATRIC DIABETES LA English DT Review DE DKA; 3 beta-OHB; sick-day management; T1D ID SUBCUTANEOUS INSULIN INFUSION; RANDOMIZED CONTROLLED-TRIAL; MULTISYSTEMIC THERAPY; CONSENSUS STATEMENT; GLYCEMIC CONTROL; YOUNG-PEOPLE; RISK-FACTORS; ADOLESCENTS; MELLITUS; ONSET AB Diabetic ketoacidosis (DKA) is an acute potentially life-threatening complication of diabetes affecting more than 100,000 persons annually in the United States. Although major advances have improved diabetes care, DKA remains the leading cause of hospitalization, morbidity, and death in youth with type 1 diabetes (T1D). As the majority of patients presenting with DKA have established diabetes, it is important to address outpatient educational approaches directed at sick-day management and early identification and treatment of impending DKA. Teaching and reinforcement of sick-day rules involves improved self-care with consistent self-monitoring of blood glucose and ketones, and timely administration of supplemental insulin and fluids. DKA as an initial manifestation of T1D may be less amendable to prevention except with an increased awareness by the lay and medical communities of the symptoms of diabetes and surveillance in high-risk populations potentially identified by family history or genetic susceptibility. New technologies that can detect the blood ketone 3 beta-hydroxybutyrate (3 beta-OHB) instead of traditional urine ketones appears to provide opportunity for early identification and treatment of impending DKA leading to reduced need for hospitalization and potential cost-savings. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Pediat Adolescent & Young, Boston, MA 02215 USA. RP Laffel, L (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Pediat Adolescent & Young, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu NR 58 TC 17 Z9 19 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD OCT PY 2007 VL 8 SU 6 BP 24 EP 33 DI 10.1111/j.1399-5448.2007.00286.x PG 10 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 207IJ UT WOS:000249244500004 PM 17727382 ER PT J AU Eichler, F Van Haren, K AF Eichler, Florian Van Haren, Keith TI Immune response in Leukodystrophies SO PEDIATRIC NEUROLOGY LA English DT Review ID X-LINKED-ADRENOLEUKODYSTROPHY; VANISHING WHITE-MATTER; UNFOLDED PROTEIN RESPONSE; CENTRAL-NERVOUS-SYSTEM; INFANTILE METACHROMATIC LEUKODYSTROPHY; MOUSE MODEL; TRANSLATION INITIATION; ASYMPTOMATIC PATIENTS; CELL TRANSPLANTATION; LESION PROGRESSION AB Although the genetics and biochemistry of leukodystrophies have been extensively explored, the immune response in these disorders has received relatively little attention. Both the disease course and its response to treatment may be highly dependent on the immune system. In this review, we compare three common leukodystrophies, each with a different immune response: (1) X-linked adrenoleukodystrophy, which demonstrates a severe, lymphocytic inflammatory response; (2) metachromatic leukodystrophy, which yields a histiocytic response; and (3) vanishing whitematter disease, in which no inflammation is typically seen. We highlight the biochemical, pathologic, and clinical differences, while focusing on the immune response in each disease. We also review the response of leukodystrophies to immunomodulatory therapies and interventions such as hematopoietic stem-cell transplantation. Future studies may delineate specific inflammatory markers as possible candidates for therapeutic intervention. (c) 2007 by Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Eichler, F (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,VBK 731, Boston, MA 02114 USA. EM feichler@partners.org NR 94 TC 21 Z9 21 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 2007 VL 37 IS 4 BP 235 EP 244 DI 10.1016/j.pediatrneurol.2007.06.011 PG 10 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 222KM UT WOS:000250295000001 PM 17903666 ER PT J AU Grave, GD Nelson, SA Walker, WA Moss, RL Dvorak, B Hamilton, FA Higgins, R Raju, TNK AF Grave, Gilman D. Nelson, Stefanie A. Walker, W. Allan Moss, R. Lawrence Dvorak, Bohuslav Hamilton, Frank A. Higgins, Rosemary Raju, Tonse N. K. TI New therapies and preventive approaches for necrotizing enterocolitis: Report of a research planning workshop SO PEDIATRIC RESEARCH LA English DT Editorial Material ID EPIDERMAL-GROWTH-FACTOR; BIRTH-WEIGHT INFANTS; REDUCES INTESTINAL APOPTOSIS; PERITONEAL DRAINAGE; NEONATAL-RATS; HUMAN-MILK; MODEL; PERFORATION; ADAPTATION; MODULATION AB The National Institute of Child Health and Human Development and the Digestive Diseases Interagency Coordinating Committee held a workshop, chaired by Dr. W. Allan Walker, on July 10-1 1. 2006 to identify promising leads in necrotizing enterocolitis (NEC) research. The goals of the workshop were to identify new approaches to the prevention and treatment of NEC, to define basic and translational mechanisms of potential approaches to NEC, and to develop recommendations for clinical studies to reduce the incidence of NEC. Workshop participants implicated prematurity, introduction of enteral feedings. gastrointestinal bacterial colonization, gut motility, proinflammatory cytokines. impaired gut blood flow, and various neonatal complications in the pathogenesis of NEC. They concluded that a unifying hypothesis encompassing these pathogenetic factors is the uncontrolled exuberant inflammatory response to bacterial colonization that characterizes the intestine of premature infants. The inflammatory cascade appears to offer multiple targets for interventions with a variety of anti-inflammatory agents. including human milk and probiotics. Because of the rapidity with which the inflammatory response gets out of control in infants with NEC, workshop participants agreed that searching for ways to prevent NEC will be more rewarding than trying to identify ways to treat the condition once it has become established. C1 NICHD, Endocrinol Nutr & Growth Branch, NIH, Bethesda, MD 20892 USA. NICHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. Sci Consulting Grp, Gaithersburg, MD 20878 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Musosal Immunol Lab, Boston, MA 02129 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA. Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ 85724 USA. NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. RP Grave, GD (reprint author), NICHD, Endocrinol Nutr & Growth Branch, NIH, 6100 Execut Blvd,Room 4B11, Bethesda, MD 20892 USA. EM graveg@mail.nih.gov NR 28 TC 95 Z9 100 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 2007 VL 62 IS 4 BP 510 EP 514 DI 10.1203/PDR.0b013e318142580a PG 5 WC Pediatrics SC Pediatrics GA 216FC UT WOS:000249862900026 PM 17667844 ER PT J AU Gordon, LB McCarten, KM Giobbie-Hurder, A Machan, JT Campbell, SE Berns, SD Kieran, MW AF Gordon, Leslie B. McCarten, Kathleen M. Giobbie-Hurder, Anita Machan, Jason T. Campbell, Susan E. Berns, Scott D. Kieran, Mark W. TI Disease progression in Hutchinson-Gilford progeria syndrome: Impact on growth and development SO PEDIATRICS LA English DT Article DE progeria; Hutchinson-Gilford progeria syndrome; developmental dysplasia; osteoporosis; clinical trial ID MUTANT LAMIN-A; SYNDROME MUTATION; MOUSE MODEL; FIBROBLASTS; DEFECTS; EXPRESSION; PHENOTYPES; CELLS; LMNA AB OBJECTIVES. Hutchinson-Gilford progeria syndrome is a rare and uniformly fatal segmental "premature aging" disease that affects a variety of organ systems. We sought to more clearly define the bone and weight abnormalities in patients with progeria as potential outcome parameters for prospective clinical trials. PATIENTS AND METHODS. We collected and analyzed longitudinal medical information, both retrospectively and prospectively, from a total of 41 children with Hutchinson-Gilford progeria syndrome spanning 14 countries, from the Progeria Research Foundation Medical and Research Database at the Brown University Center for Gerontology. RESULTS. In addition to a number of previously well-defined phenotypic findings in children with progeria, this study identified abnormalities in the eruption of secondary incisors lingually and palatally in the mandible and maxilla, respectively. Although bony structures appeared normal in early infancy, clavicular resorption, coxa valga, avascular necrosis of the femoral head, modeling abnormalities of long bones with slender diaphyses, flared metaphyses, and overgrown epiphyses developed. Long bones showed normal cortical thickness centrally and progressive focal demineralization peripherally. The most striking finding identified in the retrospective data set of 35 children was an average weight increase of only 0.44 kg/year, beginning at similar to 24 months of age and persisting through life, with remarkable intrapatient linearity. This rate is similar to 2 SD below normal weight gain for any corresponding age and sharply contrasts with the parabolic growth pattern for normal age- and gender-matched children. This finding was also confirmed prospectively. CONCLUSIONS. Our analysis shows evidence of a newly identified abnormal growth pattern for children with Hutchinson-Gilford progeria syndrome. The skeletal and dental findings are suggestive of a developmental dysplasia rather than a classical aging process. The presence of decreased and linear weight gain, maintained in all of the patients after the age of 2 years, provides the ideal parameter on which altered disease status can be assessed in clinical trials. C1 Hasbro Childrens Hosp, Dept Pediat, Providence, RI 02903 USA. Rhode Isl Hosp, Dept Pediat, Providence, RI USA. Rhode Isl Hosp, Dept Diagnost Imaging, Providence, RI USA. Rhode Isl Hosp, Dept Biostat, Providence, RI USA. Brown Univ, Warren J Alpert Med Sch, Dept Pediat, Providence, RI USA. Brown Univ, Warren J Alpert Med Sch, Dept Radiol, Providence, RI USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA USA. Dana Farber Canc Inst, Dept Computat Biol, Boston, MA USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Brown Univ, Dept Gerontol, Providence, RI USA. Childrens Hosp, Dept Pediat Hematol & Oncol, Boston, MA USA. RP Gordon, LB (reprint author), Hasbro Childrens Hosp, Dept Pediat, 593 Eddy St, Providence, RI 02903 USA. EM leslie_gordon@brown.edu RI Machan, Jason/D-3897-2013; OI Machan, Jason/0000-0003-2048-4914; Kieran, Mark/0000-0003-2184-7692 FU NIA NIH HHS [1 R21 AG021902-01] NR 43 TC 57 Z9 61 U1 0 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 2007 VL 120 IS 4 BP 824 EP 833 DI 10.1542/peds.2007-1357 PG 10 WC Pediatrics SC Pediatrics GA 216HV UT WOS:000249870000016 PM 17908770 ER PT J AU Kieran, MW Gordon, L Kleinman, M AF Kieran, Mark W. Gordon, Leslie Kleinman, Monica TI New approaches to progeria SO PEDIATRICS LA English DT Review DE progeria; premature aging; review article; farnesyltransferase inhibitor; FTI; lamin A ID HUTCHINSON-GILFORD-PROGERIA; AUTOSOMAL RECESSIVE INHERITANCE; LAMIN-A; PRELAMIN-A; SYNDROME MUTATION; DEFECTS; FARNESYLATION; PHENOTYPES; MICE; FIBROBLASTS AB Progeria (Hutchinson-Gilford progeria syndrome) is a rare genetic disorder that offers considerable insight into the biology of premature aging. This review summarizes the clinical characteristics of this disease and the underlying mutation in the lamin A (LMNA) gene that results in this phenotype. Modifications in the processing of prelamin A through alterations in farnesylation are detailed, because this pathway offers a possible drug target. Finally, discussion of an ongoing clinical trial for these children, including possible parameters for evaluation, are discussed. In the span of less than a decade, this disease has progressed from an interesting phenotype to one in which the gene defect has been identified, animal models have been created and tested with drugs that target the primary disease pathway, and significant clinical baseline data for the support of a clinical trial have been obtained. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Childrens Hosp, Dept Pediat Oncol & Critical Care, Boston, MA USA. Brown Univ, Warren Alpert Med Sch, Dept Pediat, Providence, RI USA. RP Kieran, MW (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM mark_kieran@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 40 TC 49 Z9 50 U1 3 U2 10 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 2007 VL 120 IS 4 BP 834 EP 841 DI 10.1542/peds.2007-1356 PG 8 WC Pediatrics SC Pediatrics GA 216HV UT WOS:000249870000017 PM 17908771 ER PT J AU Mazumdar, M Heeney, MM Sox, CM Lieu, TA AF Mazumdar, Maitreyi Heeney, Matthew M. Sox, Colin M. Lieu, Tracy A. TI Preventing stroke among children with sickle cell anemia: An analysis of strategies that involve transcranial Doppler testing and chronic transfusion SO PEDIATRICS LA English DT Article DE sickle cell anemia; stroke; transcranial Doppler; transfusions; health services research ID BONE-MARROW-TRANSPLANTATION; ACADEMY-OF-NEUROLOGY; RECURRENT STROKE; ISCHEMIC-STROKE; HIGH-RISK; CEREBROVASCULAR ACCIDENTS; HEALTH SUPERVISION; BLOOD-TRANSFUSIONS; IRON OVERLOAD; DISEASE AB BACKGROUND. Transcranial Doppler ultrasonography can identify children with sickle cell anemia who are at elevated risk of stroke and may benefit from chronic transfusions. Uncertainty about the risk/benefit trade-offs of chronic transfusion has led some clinicians to decide not to offer transcranial Doppler ultrasonography screening. OBJECTIVES. Our goals were to ( 1) compare the projected benefits and risks of 6 primary stroke-prevention strategies, ( 2) estimate the optimal frequency of screening, and ( 3) identify key assumptions that influence the risk/benefit relationship. METHODS. We designed a decision model to compare 6 primary stroke-prevention strategies: ( 1) annual transcranial Doppler ultrasonography screening until age 16 with children at high risk of stroke receiving monthly transfusion for life; ( 2) annual transcranial Doppler ultrasonography until age 16 with transfusions until age 18; ( 3) biannual transcranial Doppler ultrasonography until age 16 with transfusions until age 18; ( 4) annual transcranial Doppler ultrasonography until age 10 with transfusion until age 18; ( 5) 1-time screening at age 2 with transfusion until age 18; and ( 6) no intervention. Assumptions were derived from the published literature. RESULTS. For a hypothetical cohort of 2-year-old children, the optimal strategy was transcranial Doppler ultrasonography screening annually until age 10 with children at high risk receiving monthly transfusions until age 18. The optimal strategy would prevent 32% of strokes predicted to occur without intervention. The optimal strategy led to benefits similar to more intensive screening and transfusion strategies but resulted in fewer adverse events. All the intervention strategies resulted in net losses in life expectancy, because the projected mortality averted by stroke prevention was outweighed by the projected increase in mortality from transfusion. Results were sensitive to adherence rates to iron-chelation therapy. CONCLUSIONS. The optimal stroke-prevention strategy was projected to be annual transcranial Doppler ultrasonography screening until age 10 with transfusion for children at high risk until age 18. Better adherence to chelation therapy would improve life expectancy in all intervention strategies. C1 Childrens Hosp, Dept Neurol, Div Hematol Oncol, Boston, MA USA. Childrens Hosp, Dept Neurol, Dept Gen Pediat, Boston, MA USA. Harvard Pediat Hlth Serv Res Fellowship Program, Boston, MA USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Med Sch, Ctr Child Hlth Care Studies, Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. RP Mazumdar, M (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM maitreyi.mazumdar@childrens.harvard.edu RI Heeney, Matthew/J-6838-2015 OI Heeney, Matthew/0000-0002-1104-6843 FU NICHD NIH HHS [K24 HD47667]; PHS HHS [T32 HP-100063] NR 46 TC 18 Z9 18 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2007 VL 120 IS 4 BP e1107 EP E1116 DI 10.1542/peds.2006-2002 PG 10 WC Pediatrics SC Pediatrics GA 216HV UT WOS:000249870000091 PM 17768181 ER PT J AU Major, P Thiele, EA AF Major, Philippe Thiele, Elizabeth A. TI Seizures in children: Determining the variation SO PEDIATRICS IN REVIEW LA English DT Review ID PRACTICE PARAMETER C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Major, P (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 8 TC 3 Z9 3 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0191-9601 J9 PEDIATR REV JI Pediatr. Rev. PD OCT PY 2007 VL 28 IS 10 BP 363 EP 371 DI 10.1542/pir.28-10-363 PG 9 WC Pediatrics SC Pediatrics GA 217VU UT WOS:000249976200001 PM 17908858 ER PT J AU Linshaw, MA AF Linshaw, Michael A. TI Back to basics: Congenital nephrogenic diabetes insipidus SO PEDIATRICS IN REVIEW LA English DT Review C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Div Pediat Nephrol, Boston, MA 02114 USA. RP Linshaw, MA (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 9 TC 4 Z9 5 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0191-9601 J9 PEDIATR REV JI Pediatr. Rev. PD OCT PY 2007 VL 28 IS 10 BP 372 EP 380 DI 10.1542/pir.28-10-372 PG 9 WC Pediatrics SC Pediatrics GA 217VU UT WOS:000249976200002 PM 17908859 ER PT J AU Wurdinger, T Costa, FF AF Wurdinger, T. Costa, F. F. TI Molecular therapy in the microRNA era SO PHARMACOGENOMICS JOURNAL LA English DT Review DE non-coding RNAs; miRNAs; mRNA targets; multigenic diseases; cancer; 'epigenetic' therapy ID CHRONIC LYMPHOCYTIC-LEUKEMIA; SHORT-INTERFERING RNAS; HUMAN LUNG CANCERS; B-CELL LYMPHOMAS; GENE-EXPRESSION; MAMMALIAN-CELLS; IN-VIVO; MICROARRAY TECHNOLOGY; DOWN-REGULATION; NONCODING RNAS AB MicroRNAs (miRNAs) consist of a growing class of non-coding RNAs (ncRNAs) that negatively regulate the expression of genes involved in development, differentiation, proliferation, apoptosis and other important cellular processes. miRNAs are usually 18 -25 nt long and are each able to regulate several mRNAs by mechanisms such as incomplete base pairing and Post-Transcriptional Gene Silencing (PTGS). A growing number of reports have shown that aberrant miRNA expression is a common feature of human diseases including cancer, which has sparked interest in targeting these regulators of gene expression as a means of ameliorating these diseases. Here, we review important aspects of miRNA function in normal and pathological states and discuss new modalities of epigenetic intervention strategies that could be used to amend defects in miRNA/mRNA interactions. C1 Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Canc Biol & Epigenom Program, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Harvard Med Sch, Mol Neurobiol Unit, Boston, MA USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Hardvard Med Sch, Boston, MA 02114 USA. RP Costa, FF (reprint author), Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Canc Biol & Epigenom Program, 2300 Childrens Plaza,Box 220, Chicago, IL 60611 USA. EM twurdinger@partners.org; fcosta@childrensmemorial.org NR 111 TC 54 Z9 61 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD OCT PY 2007 VL 7 IS 5 BP 297 EP 304 DI 10.1038/sj.tpj.6500429 PG 8 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 216GN UT WOS:000249866600002 PM 17189960 ER PT J AU Malanga, CJ Pejchal, M Kosofsky, BE AF Malanga, C. J. Pejchal, Martina Kosofsky, Barry E. TI Prenatal exposure to cocaine alters the development of conditioned place-preference to cocaine in adult mice SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE in utero; gestation; psychostimulant; craving; place-conditioning; CPP ID IN-UTERO; BEHAVIORAL-RESPONSE; NUCLEUS-ACCUMBENS; MATERNAL SMOKING; ALCOHOL EXPOSURE; BIRTH COHORT; RATS; REWARD; DRUG; CHILDREN AB As addiction is increasingly formulated as a developmental disorder, identifying how early developmental exposures influence later responses to drugs of abuse is important to our understanding of substance abuse neurobiology. We have previously identified behavioral changes in adult mice following gestational exposure to cocaine that differ when assessed with methods employing contingent and non-contingent drug administration. We sought to clarify this distinction using a Pavlovian behavioral measure, conditioned place-preference. Adult mice exposed to cocaine in utero (40 or 20 mg/kg/day), vehicle and pair-fed controls were place-conditioned to either cocaine (5 mg/kg or 20 mg/kg, i.p.) or saline injections. The development of conditioned place-preference to cocaine was impaired in mice exposed to cocaine in utero, and was abolished by fetal malnutrition. A context-specific place-aversion to vehicle but not cocaine injection was observed in prenatally cocaine-exposed mice. Locomotor behavior did not differ among prenatal treatment groups. We conclude that early developmental exposure to cocaine may diminish the subsequent rewarding effects of cocaine in adulthood measured with classical conditioning techniques, and that this is not due to changes in locomotor behavior. Sensitivity to acute stress is also altered by prenatal cocaine exposure, consistent with earlier findings in this model. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Lab Mol & Dev Neurosci, Boston, MA 02129 USA. RP Malanga, CJ (reprint author), Univ N Carolina, Sch Med, Dept Neurol, 3114 Bioinformat Bldg,CB 7025, Chapel Hill, NC 27599 USA. EM malangacj@neurology.unc.edu; bar2009@med.cornell.edu OI Malanga, C.J./0000-0003-4808-3995 FU NIDA NIH HHS [K02 DA000354, K08 DA015429-05, R01 DA008648-08, DA008648, K02 DA000354-08, R29 DA008648, R01 DA008648, DA015429, DA000354, K08 DA015429] NR 59 TC 16 Z9 19 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD OCT PY 2007 VL 87 IS 4 BP 462 EP 471 DI 10.1016/j.pbb.2007.06.002 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 208QD UT WOS:000249333400010 PM 17644167 ER PT J AU Widlund, HR Fisher, DE AF Widlund, Hans R. Fisher, David E. TI Potent p53-independent tumor suppressor activity of ARF in melanoma-genesis SO PIGMENT CELL RESEARCH LA English DT Article ID MUTATIONS; SENESCENCE; LOCUS; NEVI; RAS; P53; RB C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Program Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. EM David_Fisher@dfci.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD OCT PY 2007 VL 20 IS 5 BP 339 EP 340 DI 10.1111/j.1600-0749.2007.00401.x PG 2 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 210CF UT WOS:000249433600004 PM 17850505 ER PT J AU Hecht, JL Kliman, HJ Allred, EN Pflueger, SM Chang, CH Doss, BJ Roberts, D Livasy, CA Bhan, I Zambrano, E Ross, DW Senagore, P Husain, AN Leviton, A AF Hecht, J. L. Kliman, H. J. Allred, E. N. Pflueger, S. M. Chang, C.-H. Doss, B. J. Roberts, D. Livasy, C. A. Bhan, I. Zambrano, E. Ross, D. W. Senagore, P. Husain, A. N. Leviton, A. TI Reference weights for placentas delivered before the 28th week of gestation SO PLACENTA LA English DT Article DE placenta; early gestation; prematurity; Chorioamnionitis; weight ID BIRTH-WEIGHT; FETAL; AGE; PREGNANCY; PATTERNS; GROWTH; RATIOS; BLOOD AB Context: Very few studies have measured the weight of large numbers of placentas delivered before the 28th post-menstrual week. Methods: We measured the weight of 930 singleton placentas delivered before the 28th post-menstrual week, and examined the distributions of weights in selected groups (week of gestation, reason for preterm birth, birth weight Z-score categories, placenta histology). We excluded 90 singleton placentas based on growth restriction as indicated by birth weight Z-score, resulting in a normative sample of 840 placentas. Weights for unfused twin placentas are also presented. Results: Standard weights derived from our data set differ from those previously published, partly due to a larger sample size. Placenta weight varied with birth weight. Placentas from pregnancies ending due to preeclampsia, fetal indications or those showing evidence of poor perfusion on histology were among the smallest and their weights correlated with the smallest birth weights for gestational age. Conclusions: Placenta weights appear to be influenced by multiple maternal and fetal processes. We present a standard weight table for singleton placentas among live infants born between 23 and 27 completed weeks. (C) 2007 Elsevier Ltd. All rights reserved. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod & Placental Res Unit, New Haven, CT USA. Childrens Hosp, Neuroepidemiol Unit, Boston, MA USA. Baystate Med Ctr, Dept Pathol, Springfield, MA USA. William Beaumont Hosp, Dept Pathol, Royal Oak, MI USA. Dept Pathol, Spectrum Hlth, Grand Rapids, MI USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC USA. Tufts Univ New England Med Ctr, Dept Pathol, Boston, MA 02111 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA. Michigan State Univ, Dept Pathol, E Lansing, MI 48824 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. RP Hecht, JL (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. EM jlhecht@bidme.harvard.edu FU NINDS NIH HHS [1 U01 NS 40069-01A2] NR 16 TC 8 Z9 8 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD OCT PY 2007 VL 28 IS 10 BP 987 EP 990 DI 10.1016/j.placenta.2007.04.009 PG 4 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 213FB UT WOS:000249650500002 PM 17573110 ER PT J AU Liao, EC Labow, BI May, JW AF Liao, Eric C. Labow, Brian I. May, James W., Jr. TI Skin banking closure technique in immediate autologous breast reconstruction SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID FLAP VIABILITY; FLUORESCEIN TEST; MASTECTOMY; COMPLICATIONS; PREDICTION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. RP May, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, 55 Fruit St, Boston, MA 02114 USA. EM jwmay@partners.org NR 20 TC 4 Z9 4 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 2007 VL 120 IS 5 BP 1133 EP 1136 DI 10.1097/01.prs.0000279144.50653.5a PG 4 WC Surgery SC Surgery GA 217VZ UT WOS:000249976700006 PM 17898586 ER PT J AU Liu, XS AF Liu, X. Shirley TI Getting started in tiling Microarray analysis SO PLOS COMPUTATIONAL BIOLOGY LA English DT Editorial Material ID TRANSCRIPTION FACTOR-BINDING; HIGH-RESOLUTION MAP; HUMAN GENOME; DNA MICROARRAYS; CHROMATIN; ARRAYS; SITES; IDENTIFICATION; METHYLATION; PROMOTERS C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Liu, XS (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM xsliu@jimmy.harvard.edu FU NHGRI NIH HHS [R01 HG004069, 1R01 HG004069-01, R01 HG004069-02] NR 25 TC 30 Z9 32 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD OCT PY 2007 VL 3 IS 10 BP 1842 EP 1844 AR e183 DI 10.1371/journal.pcbi.0030183 PG 3 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 233TP UT WOS:000251113500003 PM 17967045 ER PT J AU Listgarten, J Frahm, N Kadie, C Brander, C Heckerman, D AF Listgarten, Jennifer Frahm, Nicole Kadie, Carl Brander, Christian Heckerman, David TI A statistical framework for Modeling HLA-Dependent T cell response data SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID LYMPHOCYTE EPITOPES; BAYESIAN NETWORKS; PREDICTION; SUPERTYPES; DISCOVERY; LOAD AB The identification of T cell epitopes and their HLA (human leukocyte antigen) restrictions is important for applications such as the design of cellular vaccines for HIV. Traditional methods for such identification are costly and time-consuming. Recently, a more expeditious laboratory technique using ELISpot assays has been developed that allows for rapid screening of specific responses. However, this assay does not directly provide information concerning the HLA restriction of a response, a critical piece of information for vaccine design. Thus, we introduce, apply, and validate a statistical model for identifying HLA-restricted epitopes from ELISpot data. By looking at patterns across a broad range of donors, in conjunction with our statistical model, we can determine (probabilistically) which of the HLA alleles are likely to be responsible for the observed reactivities. Additionally, we can provide a good estimate of the number of false positives generated by our analysis (i.e., the false discovery rate). This model allows us to learn about new HLA-restricted epitopes from ELISpot data in an efficient, cost-effective, and high-throughput manner. We applied our approach to data from donors infected with HIV and identified many potential new HLA restrictions. Among 134 such predictions, six were confirmed in the lab and the remainder could not be ruled as invalid. These results shed light on the extent of HLA class I promiscuity, which has significant implications for the understanding of HLA class I antigen presentation and vaccine development. C1 Microsoft Res, Redmond, WA USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. RP Heckerman, D (reprint author), Microsoft Res, Redmond, WA USA. EM heckerma@microsoft.com OI Brander, Christian/0000-0002-0548-5778 FU PHS HHS [R01-A1-067077, N01-AL-15422] NR 27 TC 4 Z9 4 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD OCT PY 2007 VL 3 IS 10 BP 1879 EP 1886 AR e188 DI 10.1371/journal.pcbi.0030188 PG 8 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 233TP UT WOS:000251113500008 PM 17937494 ER PT J AU Wingert, RA Selleck, R Yu, J Song, HD Chen, Z Song, A Zhou, Y Thisse, B Thisse, C McMahon, AP Davidson, AJ AF Wingert, Rebecca A. Selleck, Rori Yu, Jing Song, Huai-Dong Chen, Zhu Song, Anhua Zhou, Yi Thisse, Bernard Thisse, Christine McMahon, Andrew P. Davidson, Alan J. TI The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephros SO PLOS GENETICS LA English DT Article ID PECTORAL FIN BUD; KIDNEY DEVELOPMENT; HOX GENES; VITAMIN-A; CELL FATE; TRANSPORT PROCESSES; EXPRESSION ANALYSIS; POSTERIOR AXIS; DISTAL TUBULE; HINDBRAIN AB Kidney function depends on the nephron, which comprises a blood filter, a tubule that is subdivided into functionally distinct segments, and a collecting duct. How these regions arise during development is poorly understood. The zebrafish pronephros consists of two linear nephrons that develop from the intermediate mesoderm along the length of the trunk. Here we show that, contrary to current dogma, these nephrons possess multiple proximal and distal tubule domains that resemble the organization of the mammalian nephron. We examined whether pronephric segmentation is mediated by retinoic acid (RA) and the caudal (cdx) transcription factors, which are known regulators of segmental identity during development. Inhibition of RA signaling resulted in a loss of the proximal segments and an expansion of the distal segments, while exogenous RA treatment induced proximal segment fates at the expense of distal fates. Loss of cdx function caused abrogation of distal segments, a posterior shift in the position of the pronephros, and alterations in the expression boundaries of raldh2 and cyp26a1, which encode enzymes that synthesize and degrade RA, respectively. These results suggest that the cdx genes act to localize the activity of RA along the axis, thereby determining where the pronephros forms. Consistent with this, the pronephric-positioning defect and the loss of distal tubule fate were rescued in embryos doubly-deficient for cdx and RA. These findings reveal a novel link between the RA and cdx pathways and provide a model for how pronephric nephrons are segmented and positioned along the embryonic axis. C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Shanghai Med Univ 2, Rui Jin Hosp, Shanghai Inst Hematol, Shanghai, Peoples R China. Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. IGBMC, Illkirch Graffenstaden, France. RP Davidson, AJ (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM ajdavidson@partners.org RI Song, Huai-Dong/G-8961-2011 FU NCRR NIH HHS [R01 RR015402, R01RR15402]; NIDDK NIH HHS [R01 DK054364, U01 DK070181] NR 85 TC 125 Z9 125 U1 2 U2 6 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 2007 VL 3 IS 10 BP 1922 EP 1938 DI 10.1371/journal.pgen.0030189 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 233EJ UT WOS:000251072900012 PM 17953490 ER PT J AU Bennett, GG McNeill, LH Wolin, KY Duncan, DT Puleo, E Emmons, KM AF Bennett, Gary G. McNeill, Lorna H. Wolin, Kathleen Y. Duncan, Dustin T. Puleo, Elaine Emmons, Karen M. TI Safe to walk? Neighborhood safety and physical activity among public housing residents SO PLOS MEDICINE LA English DT Article ID NUTRITION EXAMINATION SURVEY; AFRICAN-AMERICAN WOMEN; 3RD NATIONAL-HEALTH; LEISURE-TIME; UNITED-STATES; US ADULTS; SOCIOECONOMIC-STATUS; PERCEIVED SAFETY; ADOLESCENT GIRLS; NATIVE-AMERICAN AB Background Despite its health benefits, physical inactivity is pervasive, particularly among those living in lower-income urban communities. In such settings, neighborhood safety may impact willingness to be regularly physically active. We examined the association of perceived neighborhood safety with pedometer-determined physical activity and physical activity self-efficacy. Methods and Findings Participants were 1,180 predominantly racial/ethnic minority adults recruited from 12 urban low-income housing complexes in metropolitan Boston. Participants completed a 5-d pedometer data-collection protocol and self-reported their perceptions of neighborhood safety and self-efficacy (i.e., confidence in the ability to be physically active). Gender-stratified bivariate and multivariable random effects models were estimated to account for within-site clustering. Most participants reported feeling safe during the day, while just over one-third (36%) felt safe at night. We found no association between daytime safety reports and physical activity among both men and women. There was also no association between night-time safety reports and physical activity among men (p = 0.23) but women who reported feeling unsafe ( versus safe) at night showed significantly fewer steps per day (4,302 versus 5,178, p = 0.01). Perceiving one's neighborhood as unsafe during the day was associated with significantly lower odds of having high physical activity self- efficacy among both men (OR 0.40, p = 0.01) and women (OR 0.68, p = 0.02). Conclusions Residing in a neighborhood that is perceived to be unsafe at night is a barrier to regular physical activity among individuals, especially women, living in urban low-income housing. Feeling unsafe may also diminish confidence in the ability to be more physically active. Both of these factors may limit the effectiveness of physical activity promotion strategies delivered in similar settings. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Dept Hlth Disparities Res, Houston, TX USA. Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. RP Bennett, GG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM gary_bennett@dfci.harvard.edu RI Wolin, Kathleen/I-2154-2014; OI Wolin, Kathleen/0000-0001-7950-9042; Duperrex, Olivier/0000-0002-0932-6846 FU NCI NIH HHS [3R01CA098864-02S1, 5 T32 CA09001-28, 5R01CA098864-02, R01 CA098864, T32 CA009001] NR 78 TC 92 Z9 93 U1 7 U2 27 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD OCT PY 2007 VL 4 IS 10 BP 1599 EP 1607 AR e306 DI 10.1371/journal.pmed.0040306 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 233TQ UT WOS:000251113600010 PM 17958465 ER PT J AU Klenerman, P Kim, A AF Klenerman, Paul Kim, Arthur TI HCV-HIV coinfection: Simple messages from a complex disease SO PLOS MEDICINE LA English DT Article ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; CD8(+) T-CELLS; CELLULAR IMMUNE-RESPONSES; ALPHA-2A PLUS RIBAVIRIN; IN-VITRO PROLIFERATION; INJECTION-DRUG USERS; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; LIVER FIBROSIS C1 Univ Oxford, Nuffield Dept Med, Oxford, England. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. RP Klenerman, P (reprint author), Univ Oxford, Nuffield Dept Med, S Parks Rd, Oxford, England. EM paul.klenerman@ndm.ox.ac.uk FU NIAID NIH HHS [T32 AI007433]; PHS HHS [NIAID, AI07433]; Wellcome Trust NR 81 TC 24 Z9 25 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD OCT PY 2007 VL 4 IS 10 BP 1608 EP 1614 AR e240 DI 10.1371/journal.pmed.0040240 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 233TQ UT WOS:000251113600011 PM 17927445 ER PT J AU Kivisaari, R Lehtinen, R Autti, T Puuskari, V Jokela, O Ahveninen, J Rapeli, P Kahkonen, S AF Kivisaari, Reetta Lehtinen, Reia Autti, Taina Puuskari, Varpu Jokela, Olga Ahveninen, Jyrki Rapeli, Pekka Kahkonen, Seppo TI Impaired pre-attentive auditory processing in opioid dependence with and without benzodiazepine co-dependence revealed by combined magnetoencephalography and electroencephalography SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE EEG; MEG; MMN; opioid dependence ID ANTISOCIAL PERSONALITY-DISORDER; EVENT-RELATED POTENTIALS; MISMATCH NEGATIVITY; INVOLUNTARY ATTENTION; FRONTAL-CORTEX; SENSORY MEMORY; LONG-TERM; BRAIN; P300; EEG AB Cognitive dysfunctions may be a significant factor in drug-seeking behavior, reducing the efficiency of rehabilitation in opioid dependence. Neurophysiological basis of these dysfunctions is poorly understood. 21 opioid-dependent patients and 15 healthy controls with no experience of illicit drugs were studied with simultaneous electroencephalography (EEG) and magnetoencephalography (MEG). Among opioid dependents 15 were benzodiazepine co-dependent. In a passive oddball paradigm, a train of 700-Hz standard tones (80%), presented to the left ear, was occasionally interrupted by infrequent deviants, which were either 600-Hz or 400-Hz pure tones or complex novel sounds. The auditory evoked potentials (AEP) and fields (AEF) were analyzed. The strength of the N 1m dipoles was enhanced in patients with benzodiazepine co-dependence, but the latency of the response or the source location was not changed. A delay of mismatch negativity (MNM) response of novel tones in EEG, and delay of P3am response on the contralateral hemisphere to stimulated ear in MEG in opioid-dependent patients were observed. There were no differences in source locations or strengths of the dipoles for P 1m, MMNm, and P3am determined using equivalent current dipoles. There were no group differences in EEG amplitude measures. In conclusion, our results suggest delayed pre-attentive auditory processing of novel information in opioid dependence. Benzodiazepine co-dependence modulated N1m response. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Helsinki, Cent Hosp, BioMag Lab, FIN-00029 Helsinki, Finland. Univ Helsinki, Cent Hosp, Med Imaging Ctr, FI-00029 Helsinki, Finland. Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, Helsinki, Finland. Univ Helsinki, Dept Psychol, Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Psychiat, Helsinki, Finland. MIT, Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. RP Kahkonen, S (reprint author), Univ Helsinki, Cent Hosp, BioMag Lab, PO Box 340, FIN-00029 Helsinki, Finland. EM seppo.kahkonen@helsinki.fi OI Rapeli, Pekka/0000-0003-3982-1685 NR 46 TC 5 Z9 5 U1 0 U2 7 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 2007 VL 31 IS 7 BP 1378 EP 1386 DI 10.1016/j.pnpbp.2007.06.001 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 213PH UT WOS:000249679100005 PM 17614180 ER PT J AU Kornblith, AB Powell, M Regan, MM Bennett, S Krasner, C Moy, B Younger, J Goodman, A Berkowitz, R Winer, E AF Kornblith, Alice B. Powell, Mark Regan, Meredith M. Bennett, Samantha Krasner, Carolyn Moy, Beverly Younger, Jerry Goodman, Annekathym Berkowitz, Ross Winer, Eric TI Long-term psychosocial adjustment of older vs younger survivors of breast and endometrial cancer SO PSYCHO-ONCOLOGY LA English DT Article DE survivor; adaptation; elderly; breast; endometrial ID QUALITY-OF-LIFE; LEUKEMIA SURVIVORS; MENTAL-HEALTH; BODY-IMAGE; WOMEN; DISEASE; DIAGNOSIS; IMPACT; AGE; PREVALENCE AB Background: The study's objective was to test whether there were significant differences in adjustment between younger and older breast and endometrial cancer survivors. Methods: Two hundred and fifty-two breast and endometrial cancer survivors participated in this study, ranging in age from either 18 to 55 years old or 65 years old or older. Survivors were interviewed by telephone at study entry and 12 months, using a battery of measures to assess their adjustment, physical functioning, and treatment-related physical problems. Results: With an average of 3.7 years since treatment completion, almost all survivors reported good adjustment to having had cancer. While most differences in psychosocial adjustment between groups were small, younger survivors reported significantly worse adaptation than older survivors, as measured by the Hospital Anxiety and Depression Scale (HADS, p<0.0001), Appearance-Orientation Scale (AOS, body image; p = 0.02), Fear of Recurrence (p<0.0001), Distress about Long-term Treatment-Related Cancer Problems (p = 0.01), and Number of Sexual Problems Attributed to Cancer (P < 0.0001). Conclusion: Survivors reported few cancer-related problems with only a small subset reporting problems in adjustment. Although differences were small, younger cancer survivors reported significantly worse adaptation than older survivors. Much of the adaptation to having had cancer may have already occurred in long-term survivors. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 Dana Farber Canc Inst, Breast Oncol Program Mayer 2, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kornblith, AB (reprint author), Dana Farber Canc Inst, Breast Oncol Program Mayer 2, 44 Binney St, Boston, MA 02115 USA. EM Komblith@dfci.harvard.edu NR 39 TC 87 Z9 89 U1 0 U2 4 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 2007 VL 16 IS 10 BP 895 EP 903 DI 10.1002/pon.1146 PG 9 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 224EK UT WOS:000250430100003 PM 17245695 ER PT J AU Pollack, M Mangano, R Entsuah, R Tzanis, E Simon, NM AF Pollack, Mark Mangano, Richard Entsuah, Richard Tzanis, Evan Simon, Naomi M. TI A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder SO PSYCHOPHARMACOLOGY LA English DT Article DE venlafaxine; paroxetine; panic disorder; agoraphobia; pharmacotherapy; panic attack ID SOCIAL ANXIETY DISORDER; PLACEBO-CONTROLLED TRIAL; EXTENDED-RELEASE CAPSULES; DOUBLE-BLIND; MAJOR DEPRESSION; DOSE-RESPONSE; NONDEPRESSED OUTPATIENTS; TERM TREATMENT; SINGLE-BLIND; PRIMARY-CARE AB Rationale Few randomized, placebo-controlled trials have evaluated the comparative efficacy and tolerability of more than one pharmacological agent for panic disorder. Objectives The primary objective of this study was to compare the efficacy and tolerability of venlafaxine extended release (ER) with placebo in treating panic disorder. Secondary objectives included comparing paroxetine with venlafaxine ER and placebo. Methods Outpatients aged >= 18 years (placebo, n=157; venlafaxine ER 75 mg, n=156; venlafaxine ER 225 mg, n=160; paroxetine, n=151), with a primary diagnosis of panic disorder (+/- agoraphobia) based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for >= 3 months were randomly assigned to receive venlafaxine ER (titrated to 75 mg/day or 225 mg/day), paroxetine (titrated to 40 mg/day), or placebo for 12 weeks. The primary efficacy measure was the percentage of patients free of full-symptom panic attacks (>= four symptoms) at endpoint. Key secondary outcomes included the Panic Disorder Severity Scale (PDSS) mean score change and response. Results At endpoint, all active treatment groups showed a significantly (P < 0.01) greater proportion of patients free of full-symptom panic attacks, compared with placebo, and were superior (P < 0.05) on most secondary measures. The venlafaxine ER 225 mg group had significantly (P < 0.05) greater mean PDSS score improvement than the paroxetine group (-12.58 vs -11.87) and a significantly higher proportion of patients free of full symptom panic attacks (70.0 vs 58.3%). Both drugs were generally well tolerated. Conclusion Venlafaxine ER 75 mg/days and 225 mg/days and paroxetine 40 mg/day were both well tolerated and effective for short-term treatment of panic disorder. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Wyeth Ayerst Res, Collegeville, PA USA. RP Pollack, M (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Suite 2200,2nd, Boston, MA 02114 USA. EM mpollack@partners.org NR 63 TC 35 Z9 37 U1 4 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2007 VL 194 IS 2 BP 233 EP 242 DI 10.1007/s00213-007-0821-0 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 212XJ UT WOS:000249630000009 PM 17589833 ER PT J AU Doyle, PJ McNeil, MR Bost, JE Ross, KB Wambaugh, JL Hula, WD Mikolic, JM AF Doyle, Patrick J. McNeil, Malcolm R. Bost, James E. Ross, Katherine B. Wambaugh, Julie L. Hula, William D. Mikolic, Joseph M. TI The Burden of Stroke Scale (BOSS) provided valid, reliable, and responsive score estimates of functioning and well-being during the first year of recovery from stroke SO QUALITY OF LIFE RESEARCH LA English DT Article DE stroke; health-status; health-related quality of life; patient-reported outcomes (PROs); responsiveness; functioning; well-being ID QUALITY-OF-LIFE; HEALTH SURVEY SF-36; NEGATIVE AFFECT; IMPACT SCALE; RELIABILITY; INDEPENDENCE; SURVIVORS; VERSION; TESTS AB Ojectives To examine the reliability, validity, and responsiveness of the Burden of Stroke Scale (BOSS). Study Design A prospective cohort of stroke survivors were assessed at 3 (T1, T2), 6 (T3), and 12 (T4) months post onset (MPO) of stroke. Test-retest reliability was evaluated by calculating intra-class correlation coefficients (ICCs) between T1 and T2 scale scores. Convergent validity was evaluated by calculating Pearson product moment correlation coefficients between T1 BOSS, Stroke Impact Scale and MOS SF-36 scale scores assessing similar health concepts. Responsiveness was evaluated using a repeated measures ANOVA and the linear trend test in the full study sample and by calculating standardized response means (SRM) and a probability of change statistic, (p) over cap between T1, T3, and T4 scale scores in participants demonstrating change on external criteria. Results ICCs ranged from 0.78 to 0.94. Pearson coefficients ranged from -0.57 to -0.86. Moderate to high responsiveness estimates were obtained for 9 of 12 subscales with SRM ((p) over cap )values ranged from .497 (.690) to 1.161 (.877). Composite scale SRM ((p) over cap) values ranged from .661 (.746) to 1.192 (.883). Conclusions The BOSS provided valid and reliable score estimates that were responsive to positive changes in functioning and well-being during the first year of recovery from stroke. C1 VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Carl T Hayden VA Med Ctr, Phoenix, AZ USA. VA Salt Lake City Healthcare Syst, Salt Lake City, UT USA. Novum Pharmaceut Res Serv, Pittsburgh, PA USA. RP Doyle, PJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM patrick.doyle@med.va.gov NR 45 TC 10 Z9 10 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT PY 2007 VL 16 IS 8 BP 1389 EP 1398 DI 10.1007/s11136-007-9247-8 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 212XK UT WOS:000249630100012 PM 17665314 ER PT J AU Visser, JJ van Sambeek, MRHM Hamza, TH Hunink, MGM Bosch, JL AF Visser, Jacob J. van Sambeek, Marc R. H. M. Hamza, Taye H. Hunink, M. G. Myriam Bosch, Johanna L. TI Ruptured abdominal aortic aneurysms: Endovascular repair versus open surgery-systematic review SO RADIOLOGY LA English DT Review ID RANDOMIZED CONTROLLED TRIALS; CONVENTIONAL OPEN REPAIR; CLINICAL-TRIALS; FEASIBILITY; EXPERIENCE; BIAS AB Purpose: To perform a systematic review of studies in which endovascular repair was compared with open surgery in the treatment of patients with a ruptured abdominal aortic aneurysm (AAA). Materials and Methods: A search of the English-language literature from January 1994 until March 2006 was performed. Inclusion criteria for studies were that they were about a comparison between patients who underwent endovascular repair and patients who underwent open surgery, that each treatment group included at least five patients, that information about patients' hemodynamic condition at presentation was reported, and that 30-day mortality was reported for each treatment group. Two reviewers independently extracted the data, and discrepancies were resolved by an tit-biter. Random-effects models and meta-regression analysis were used to calculate crude and adjusted odds ratios (ORs) for endovascular repair versus open surgery. Results: Ten studies, in which the results of 478 procedures (n = 148 for endovascular repair, n = 330 for open surgery) were reported, met the inclusion criteria. All studies were observational; no randomized controlled trials were found. The pooled 30-day mortality was 22% (95% confidence interval [CI]: 16%, 29%) for endovascular repair and 38% (95% CI: 32%, 45%) for open surgery. The pooled rate for total systemic complications was 28% (95% CI: 17%, 48%) for endovascular repair and 56% (95% CI: 37%, 85%) for open surgery. The crude OR for 30-day mortality for endovascular repair compared with open surgery was 0.45 (95% CI: 0.28, 0.72). After adjustment for patients' hemodynamic condition, the OR was 0.67 (95% CI: 0.31, 1.44). Conclusion: In this systematic review, after adjustment for patients' hemodynamic condition at presentation, a benefit in 30-day mortality for endovascular repair compared with open surgery for patients with a ruptured AAA was observed, but it was not statistically significant. C1 Erasmus MC, Dept Epidemiol & Biostat, NL-3015 GD Rotterdam, Netherlands. Erasmus MC, Dept Radiol, NL-3015 GD Rotterdam, Netherlands. Erasmus MC, Dept Surg, NL-3015 GD Rotterdam, Netherlands. Harvard Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. Harvard Univ, Inst Technol Assessment, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bosch, JL (reprint author), Erasmus MC, Dept Epidemiol & Biostat, Dr Molewaterpl 40,Room Ee21-40B, NL-3015 GD Rotterdam, Netherlands. EM j.l.bosch@erasmusmc.nl NR 36 TC 59 Z9 61 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2007 VL 245 IS 1 BP 122 EP 129 DI 10.1148/radiol.2451061204 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 212EX UT WOS:000249577500015 PM 17885185 ER PT J AU Hess, DR AF Hess, Dean R. TI Airway clearance: Physiology, pharmacology, techniques, and practice SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 39th Conference of the Respiratory-Care-Journal CY 2007 CL Orlando, FL SP Respiratory Care Journal DE airway clearance; chest physiotherapy; cough; mucus clearance therapy AB Clinicians and their patients are troubled by respiratory secretions, and standard practice calls for efforts to clear secretions from the lungs. On one hand, mucus production and cough are important for airway defense and protection of the lower respiratory tract against inhaled irritations. On the other hand, excessive mucus obstructs airways and excessive cough has been associated with a number of complications. The objective of this conference was to review the scientific basis and clinical evidence for the use of airway clearance therapy to guide the most appropriate approach to airway clearance. An international group of clinicians and scientists addressed the physiology of mucus production and cough, pharmacologic approaches to airway clearance, and the variety of techniques available for airway clearance. Specific issues related to airway clearance in critically ill patients, children, and the elderly were discussed. Outcome measures related to evaluating mucus clearance therapy were also presented. One of the themes repeated consistently throughout this conference was the dearth of high-level evidence related to airway clearance techniques. Appropriately powered and methodologically sound research is desperately needed in this area. C1 Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 9 TC 12 Z9 13 U1 1 U2 3 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD OCT PY 2007 VL 52 IS 10 BP 1392 EP 1396 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 219BF UT WOS:000250059000007 PM 17894906 ER PT J AU Cruz-Gonzalez, I Sanchez-Ledesma, M Sanchez, PL Jang, IK AF Cruz-Gonzalez, Ignacio Sanchez-Ledesma, Maria Sanchez, Pedro L. Jang, Ik-Kyung TI Heparin-induced thrombocytopenia SO REVISTA ESPANOLA DE CARDIOLOGIA LA Spanish DT Review DE heparin-induced thrombocytopenia; diagnosis; treatment ID MOLECULAR-WEIGHT HEPARIN; PERCUTANEOUS CORONARY INTERVENTION; GLYCOPROTEIN IIB/IIIA RECEPTOR; VENOUS LIMB GANGRENE; RECOMBINANT HIRUDIN; ARGATROBAN ANTICOAGULATION; UNFRACTIONATED HEPARIN; CARDIOPULMONARY BYPASS; FACTOR-4 ANTIBODIES; PROSPECTIVE COHORT AB Hemorrhage is the most common and best-recognized complication of heparin treatment. However, a potentially more dangerous complication is the development of heparin-induced thrombocytopenia (HIT). All patients exposed to heparin, irrespective of the dose and route of administration, are at risk of developing HIT. It is due to the formation of antibodies against the heparin-platelet factor 4 complex, which cause secondary activation of platelets, coagulation and, finally, increased thrombin production. The main symptom is the sudden onset of thrombocytopenia involving a drop in the platelet count to less than 50% of the basal level, with or without the appearance of thrombotic complications some 5 to 14 days after the start of heparin therapy. Heparin-induced thrombocytopenia can be detected early in patients receiving heparin by monitoring the platelet count. Demonstration of heparin-dependent platelet activation using an antigen or functional assay confirms the clinical diagnosis. Once the diagnosis of HIT has been confirmed serologically or there is a high level of suspicion of HIT, heparin must be suspended and treatment with an alternative anticoagulant should be considered. This review contains a discussion of the diagnosis and treatment of this syndrome. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. Univ Gregorio Maranon, Gen Hosp, Serv Cardiol, Madrid, Spain. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 84 TC 5 Z9 7 U1 0 U2 0 PU EDICIONES DOYMA S/L PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD OCT PY 2007 VL 60 IS 10 BP 1071 EP 1082 DI 10.1157/13111239 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 223ZF UT WOS:000250414100011 PM 17953929 ER PT J AU Kastrinos, F Syngal, S AF Kastrinos, Fay Syngal, Sapna TI Recently identified colon cancer predispositions: MYH and MSH6 mutations SO SEMINARS IN ONCOLOGY LA English DT Review ID NONPOLYPOSIS COLORECTAL-CANCER; FAMILIAL ADENOMATOUS POLYPOSIS; SOMATIC G-C->T-A MUTATIONS; REPAIR-GENE-MUTATIONS; GERMLINE MUTATIONS; MISMATCH-REPAIR; LYNCH-SYNDROME; MICROSATELLITE INSTABILITY; BETHESDA GUIDELINES; RISK AB Single-gene germline mutations conferring a high lifetime risk of colorectal cancer (CRC) account for up to 6% of all CRC cases. The most widely studied monogenic colorectal cancer syndromes include familial adenomatous polyposis (FAP) and Lynch syndrome. However, additional syndromes continue to be defined and new predisposition genes are continuing to be identified. Most recently, MYH-associated polyposis (MAP) and an "a typical Lynch syndrome" related to the presence of MSH6 mutations have been linked to an increased risk of CRC. In this review, we summarize basic information related to these newly recognized gene mutations, including the accumulating data on the prevalence and penetrance of deleterious mutations, as well as the management options for identified carriers and their families. Recognizing these heritable syndromes is essential and predictive genetic testing will continue to transform the field of cancer risk assessment by offering the opportunity to focus on more precise risk management and cancer prevention. C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 1 Jimmy Fudn Way,SM 209, Boston, MA 02115 USA. EM ssyngal@partners.org FU NCI NIH HHS [R01 CA085759-01A1, K24 CA113433-02, R01 CA085759-02, K24 CA113433-03, R01 CA085759, R01 CA085759-04, K24 CA113433, R01 CA085759-03, K24 CA113433-01] NR 65 TC 16 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2007 VL 34 IS 5 BP 418 EP 424 DI 10.1053/j.seminoncol.2007.07.005 PG 7 WC Oncology SC Oncology GA 224BE UT WOS:000250419500009 PM 17920897 ER PT J AU Murakami, K Enkhbaatar, P Yu, YM Traber, LD Cox, RA Hawkins, HK Tompkins, RG Herndon, D Traber, DL AF Murakami, Kazunori Enkhbaatar, Perenlei Yu, Yong-Ming Traber, Lillian D. Cox, Robert A. Hawkins, Hal K. Tompkins, Ronald G. Herndon, David Traber, Daniel L. TI L-arginine attenuates acute lung injury after smoke inhalation and burn injury in sheep SO SHOCK LA English DT Article DE NO; ARDS; airway obstruction; thermal injury; arginine ID NITRIC-OXIDE SYNTHASE; PULMONARY-EDEMA; SEPSIS; MODEL; PEROXYNITRITE; INHIBITOR; MACROPHAGES; PERFORMANCE; FAILURE; PATHWAY AB Thermal injury results in reduced plasma levels of arginine(Arg). With reduced Arg availability, NOS produces superoxide instead of NO. We hypothesized that Arg supplementation after burn and smoke inhalation (B + S) injury would attenuate the acute insult to the lungs and, thus, protect pulmonary function. Seventeen Suffolk ewes (n = 17) were randomly divided into three groups: (1) sham injury group (n = 6), (2) B + S injury plus saline treatment (n = 6), and (3) B + S injury Plus L-ARG infusion at 57 mg.kg(-1).h(-1) (n = 5). Burn and smoke inhalation injury was induced by standardized procedures, including a 40% area full thickness flame burn combined with 48 breaths of smoke from burning cottons. All animals were immediately resuscitated by Ringer solution and supported by mechanical ventilation for 48 h, during which various variables of pulmonary function were monitored. The results demonstrated that Arg treatment attenuated the decline of plasma Arg concentration after B + S injury. A higher plasma Arg concentration was associated with a less decline in PaO2/FIO2 ratio and a reduced extent of airway obstruction after B + S injury. Histopathological examinations also indicated a remarkably reduced histopathological scores associated with B + S injury. Nitrotyrosine stain in lung tissue was positive after B + S injury, but was significantly reduced in the group with Arg. Therefore, L-Arg supplementation improved gas exchange and pulmonary function in ovine after B + S injury via its, at least in part, effect on reduction of oxidative stress through the peroxynitrite pathway. C1 Univ Texas, Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA. Shriners Hosp Children, Galveston, TX 77550 USA. Massachusetts Gen Hosp, Boston, MA USA. Shriners Burns Hosp, Boston, MA USA. RP Enkhbaatar, P (reprint author), Univ Texas, Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA. EM peenkhba@utmb.edu FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-12] NR 35 TC 17 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD OCT PY 2007 VL 28 IS 4 BP 477 EP 483 DI 10.1097/shk.0b013e31804a59bd PG 7 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 214XL UT WOS:000249771500016 PM 17558346 ER PT J AU Hoch, B Hermann, G Klein, MJ Abdelwahab, IF Springfield, D AF Hoch, Benjamin Hermann, George Klein, Michael J. Abdelwahab, Ibrahim Fikry Springfield, Dempsey TI Giant cell tumor complicating Paget disease of long bone SO SKELETAL RADIOLOGY LA English DT Article DE giant cell tumor; Paget disease; bone tumor ID PATHOLOGICAL CORRELATION; INTRANUCLEAR INCLUSIONS; REPARATIVE GRANULOMA; ETIOLOGY; ARCHIVES; SARCOMAS; AFIP AB Giant cell tumor (GCT) is a rare complication of Paget disease of bone. It usually occurs in the skull or pelvic bones of patients with long-standing polyostotic disease. This report describes a 62-year-old patient who presented with monostotic Paget disease of the distal femur complicated by GCT. He had a 2-year history of discomfort and pain in his left knee. Conventional plain films and MRI demonstrated the characteristic bone changes of Paget disease and an associated lytic lesion involving the epiphyseal and metaphyseal regions of the distal femur. A diagnostic curettage showed the characteristic histopathologic features of Paget disease and GCT. There was no evidence of malignancy. The clinicopathologic features of this rare lesion are described and correlated with a review of the literature. C1 Mt Sinai Med Ctr, Dept Pathol, New York, NY USA. Mt Sinai Med Ctr, Dept Radiol, New York, NY 10029 USA. Univ Alabama, Sch Med, Dept Pathol, Birmingham, AL USA. CUNY, Downstate Sch Med, Coney Isl Hosp, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Hoch, B (reprint author), Mt Sinai Med Ctr, Dept Pathol, 1 Gustave L Levy Pl,Box 1194, New York, NY USA. EM benjamin.hoch@mountsinai.org NR 35 TC 11 Z9 13 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD OCT PY 2007 VL 36 IS 10 BP 973 EP 978 DI 10.1007/s00256-007-0310-x PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 208JY UT WOS:000249316800012 PM 17437100 ER PT J AU Kobashi, Y Schoenbaum, A Hasserjian, RP Rosenthal, DI AF Kobashi, Yuko Schoenbaum, Amy Hasserjian, Robert P. Rosenthal, Daniel I. TI Berardinelli-Seip lipodystrophy SO SKELETAL RADIOLOGY LA English DT Article DE lipodystrophy; congenital; MRI; CT ID CONGENITAL LIPODYSTROPHY; MARROW AB Berardinelli-Seip lipodystrophy (BSCL) is a rare, but widely distributed, congenital disorder of metabolism. It is characterized by insulin-resistant diabetes mellitus and marked deficiency of adipose tissue. The clinical and imaging features of the syndrome are mostly due to fat deficiency, diabetes, or to manifestations of secondary hyperinsulinemia, which results from the failure of the tissues to respond to insulin. Absence of fat may be generalized, or depending upon the subtype of the disease, may not affect areas where fat plays a mechanical function, such as the palms and soles. Muscles appear hypertrophic. In addition, characteristic, but idiopathic, peri-articular lytic lesions may be seen in some individuals. The combination of imaging, clinical, and laboratory findings is characteristic and readily recognized once the components of the syndrome are known. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. St Marianna Univ, Sch Med, Dept Radiol, Kawasaki, Kanagawa 2618511, Japan. RP Rosenthal, DI (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM DIRosenthal@partners.org NR 14 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD OCT PY 2007 VL 36 IS 10 BP 999 EP 1003 DI 10.1007/s00256-007-0332-4 PG 5 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 208JY UT WOS:000249316800017 PM 17554536 ER PT J AU Inagami, S Cohen, DA Finch, BK AF Inagami, Sanae Cohen, Deborah A. Finch, Brian K. TI Non-residential neighborhood exposures suppress neighborhood effects on self-rated health SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE self-rated health; multi-level modeling; neighborhood; disadvantage; mobility; USA ID CORONARY HEART-DISEASE; SOCIOECONOMIC CONTEXT; ATHEROSCLEROSIS RISK; MULTILEVEL ANALYSIS; ALLOSTATIC LOAD; TRAVEL BEHAVIOR; MENTAL-HEALTH; DEPRIVATION; MORTALITY; COMMUNITY AB In prior research, neighborhood effects have often been weak or inconsistent in predicting specific causes of mortality and morbidity. To determine whether residential neighborhood effects are suppressed by exposure to other environments, we examined the effect on adult self-rated health of non-residential environments that figure in individuals' daily routines. We linked the 2000 US Census data with the Los Angeles Family and Neighborhood Study (L.A.FANS) database, which consists of 3323 adults sampled from neighborhoods in LA County. Characteristics of census tracts where respondents lived, worked, shopped, sought medical care, worshipped and spent "other" time were obtained from the 2000 US Census. Weighted multilevel linear and clustered generalized ordered logistic regressions were used to estimate associations between self-rated health and non-residential neighborhood exposures after adjustment for individual-level factors and exposure to residential neighborhoods. We found that residence in disadvantaged neighborhoods was associated with worse self-rated health. In a dose-response fashion, the greater the exposure to less disadvantaged non-residential neighborhoods in the course of routine activities, the greater the magnitude in improved self-rated health. Models including non-residential neighborhood exposure increase the magnitude and significance of the association between residential neighborhoods and health. In conclusion, individuals' exposure to non-residential neighborhoods confounds and suppresses the association of residential neighborhoods with health and could explain why previous studies may not have found robust associations between residential neighborhood predictors and health. Published by Elsevier Ltd. C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Inagami, S (reprint author), VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. EM sinagami@ucla.edu; deborah_cohen@rand.org; bfinch@mail.sdsu.edu NR 60 TC 85 Z9 87 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD OCT PY 2007 VL 65 IS 8 BP 1779 EP 1791 DI 10.1016/j.socscimed.2007.05.051 PG 13 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 222BP UT WOS:000250271400020 PM 17614175 ER PT J AU Ioannou, GN Spector, J Rockey, DC AF Ioannou, George N. Spector, Jeremy Rockey, Don C. TI Predictors of endoscopic and laboratory evaluation of iron deficiency anemia in hospitalized patients SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE colonoscopy; esophagogastroduodenoscopy; ferritin; gastrointestinal bleeding ID GASTROINTESTINAL-TRACT; DIAGNOSIS AB Background: Many hospitalized anemic patients do not undergo appropriate evaluation. We hypothesized that specific clinical variables were likely to be important in triggering evaluation for iron deficiency anemia. Methods: We prospectively identified 637 consecutive anemic patients without acute gastrointestinal bleeding admitted over a three-month period to medical inpatient teams of two teaching hospitals and examined clinical variables that predicted diagnostic evaluation. Results: Serum ferritin or serum transferrin saturation (TS) were measured in 43% (271/637) of subjects and were low in 38% (102/ 271). Predictors of serum ferritin or TS measurement included low hemoglobin concentration and a history of iron supplementation, Predictors of iron deficiency included low hemoglobin concentration (OR 1.9,95% CI 1.06-3.5) and low mean cell volume (OR 4.6, 95% CI 2.5- 8.6). Of 102 patients with iron deficiency anemia, 3 1% underwent endoscopic evaluation, and 39% had serious gastrointestinal lesions. The only significant predictor of having an endoscopic evaluation was a positive fecal occult blood test (FOBT) (OR 5.2, 95% CI 1.7-16.2). Conclusions: In patients with anemia, tests to ascertain iron status are not appropriately performed in hospitalized patients. Patients found to have iron deficiency anemia who are FOBT-positive undergo endoscopic evaluation more frequently than FOBT-negative patients. C1 Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Med, Dallas, TX 75390 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC USA. Duke Univ, Med Ctr, Div Gastroenterol, Durham, NC USA. Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA USA. RP Rockey, DC (reprint author), Univ Texas, SW Med Ctr, Div Digest & Liver Dis, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM don.rockey@utsouthwestern.edu NR 18 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD OCT PY 2007 VL 100 IS 10 BP 976 EP 984 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 222BS UT WOS:000250271700010 PM 17943040 ER PT J AU Hunt, D AF Hunt, Dan TI Determining the clinical probability of deep venous thrombosis and pulmonary embolism SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE clinical prediction rules; deep venous thrombosis; pulmonary embolism ID VEIN THROMBOSIS; D-DIMER; PRETEST PROBABILITY; COMPUTED-TOMOGRAPHY; PREDICTION RULES; EMERGENCY-DEPARTMENT; PRIMARY-CARE; DIAGNOSIS; MANAGEMENT; SCORE AB Deep venous thrombosis and pulmonary embolism are potentially life-threatening problems that present diagnostic challenges. To employ objective diagnostic tests in an efficient, safe, and cost-effective manner, the clinical probability of these disorders should be estimated before testing. A number of clinical prediction rules are available for suspected deep venous thrombosis, while there are three major prediction rules available for estimating the probability of pulmonary embolism. Recent modifications of the Wells score for deep venous thrombosis simplify its use. Although the Wells score for pulmonary embolism is commonly used, two other rules are useful for this disorder as well. This review summarizes the clinical prediction rules and gives recommendations about their application. C1 Massachusetts Gen Hosp, Dept Med, Inpatient Clin Educator Serv, Boston, MA 02114 USA. RP Hunt, D (reprint author), Massachusetts Gen Hosp, Dept Med, Inpatient Clin Educator Serv, 50 Staniford St,Suite 503b, Boston, MA 02114 USA. EM dphunt@partners.org NR 42 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD OCT PY 2007 VL 100 IS 10 BP 1015 EP 1021 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 222BS UT WOS:000250271700015 PM 17943048 ER PT J AU Li, Y Shih, MC Betensky, RA AF Li, Yi Shih, Mei-Chiung Betensky, Rebecca A. TI Designed extension of survival studies: Application to clinical trials with unrecognized heterogeneity SO STATISTICA SINICA LA English DT Article DE adaptive design; conditional power; frailty model ID SAMPLE-SIZE; MODELS; POWER AB It is well known that unrecognized heterogeneity among patients, such as is conferred by genetic subtype, can undermine the power of a randomized trial, designed under the assumption of homogeneity, to detect a truly beneficial treatment. We consider the conditional power approach to allow for recovery of power under unexplained heterogeneity. While Proschan and Hunsberger (1995) confined the application of conditional power design to normally distributed observations, we consider more general and difficult settings in which the data are in the framework of continuous time and are subject to censoring. In particular, we derive a procedure appropriate for the analysis of the weighted log rank test under the assumption of a proportional hazards frailty model. The proposed method is illustrated through application to a brain tumor trial. C1 Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Li, Y (reprint author), Harvard Univ, Dana Farber Canc Inst, 44 Binney St,LW211, Boston, MA 02115 USA. EM yili@jimmy.harvard.edu; meichiun@standford.odu; betensky@hsph.harvard.edu NR 13 TC 0 Z9 0 U1 1 U2 1 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 2007 VL 17 IS 4 BP 1567 EP 1589 PG 23 WC Statistics & Probability SC Mathematics GA 230PK UT WOS:000250888200017 ER PT J AU Phillips, SJ Dai, D Mitnitski, A Gubitz, GJ Johnston, KC Koroshetz, WJ Furie, KL Black, S Heiselman, DE AF Phillips, Stephen J. Dai, Dingwei Mitnitski, Arnold Gubitz, Gordon J. Johnston, Karen C. Koroshetz, Walter J. Furie, Karen L. Black, Sandra Heiselman, Darell E. CA GAIN Americas Investigators TI Clinical diagnosis of Lacunar stroke in the first 6 hours after symptom onset - Analysis of data from the glycine antagonist in neuroprotection (GAIN) Americas trial SO STROKE LA English DT Article DE lacunar infarction; stroke assessment; stroke classification; stroke outcome ID ACUTE ISCHEMIC-STROKE; SCALE RANDOMIZED EVIDENCE; ACUTE CEREBRAL INFARCTION; DIFFUSION-WEIGHTED MRI; COMPUTED-TOMOGRAPHY; CLASSIFICATION; HYPOTHESIS; COMMUNITY; ACCURACY; VALIDITY AB Background and Purpose - Although the pathophysiological heterogeneity of stroke may be highly relevant to the development of acute-phase therapies, discriminating between ischemic stroke subtypes soon after onset remains a challenge. We conducted a study of the accuracy of a clinical diagnosis of lacunar stroke in the first 6 hours after symptom onset. Methods - We analyzed data from 1367 patients in the Glycine Antagonist In Neuroprotection (GAIN) Americas trial. The Trial of ORG10172 in Acute Stroke Treatment (TOAST) category " small vessel (lacunar)" disease at day 7 or at hospital discharge was used as the reference standard to determine the accuracy of a diagnosis of a lacunar stroke made within 6 hours of symptom onset using the Oxfordshire Community Stroke Project (OCSP) classification " LACS." Outcome was analyzed by comparing the proportions of patients classified as " LACS" at baseline or " small vessel (lacunar)" at 7 days who were dead or dependent at 3 months. Results - The positive predictive value of an OCSP diagnosis of a lacunar stroke was 76% (95% CI: 69% to 81%; sensitivity 64% [95% CI: 58% to 70%]; specificity 96% [95% CI: 95% to 97%]; negative predictive value 93% [95% CI: 92% to 94%]; accuracy 91% [95% CI: 89% to 92%]). The 3-month outcomes of patients classified as either OCSP " LACS" within 6 hours of onset or TOAST " small vessel (lacunar)" at 7 days were not significantly different. Conclusions - An OCSP LACS diagnosis made within 6 hours of stroke onset is reasonably predictive of a final diagnosis of " small vessel (lacunar)" disease made using TOAST criteria and has a similar relationship to outcome at 3 months. C1 Dalhousie Univ, Queen Elizabeth II Hlt Sci Ctr, Halifax, NS, Canada. Dalhousie Univ, Dept Med, Halifax, NS, Canada. Dalhousie Univ, Dept Epidemiol & Community Hlth, Halifax, NS, Canada. Univ Virginia, Charlottesville, VA USA. NINDS, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Toronto, Toronto, ON, Canada. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. Akron Gen Med Ctr, Akron, OH USA. RP Phillips, SJ (reprint author), Div Neurol, Halifax Infirmary Room 3831,1796 Summer St, Halifax, NS B3H 3A7, Canada. EM stephen.phillips@dal.ca OI Black, Sandra/0000-0001-7093-8289 FU NINDS NIH HHS [R01 NS050192, R01 NS050192-02] NR 38 TC 9 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2007 VL 38 IS 10 BP 2706 EP 2711 DI 10.1161/STROKEAHA.107.487744 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 213VJ UT WOS:000249694900016 PM 17717313 ER PT J AU Iwai, M Cao, GD Yin, W Stetler, RA Liu, JL Chen, J AF Iwai, Masanori Cao, Guodong Yin, Wei Stetler, R. Anne Liu, Jialing Chen, Jun TI Erythropoietin promotes neuronal replacement through revascularization and neurogenesis after neonatal hypoxia/ischemia in rats SO STROKE LA English DT Article DE erythropoietin; neonatal hypoxia/ischemia; neurogenesis; neuronal replacement; revascularization ID NEURAL STEM-CELLS; HYPOXIC-ISCHEMIC INJURY; SUBVENTRICULAR ZONE; BRAIN-INJURY; ENHANCES NEUROGENESIS; STROKE; PROGENITORS; MOUSE; ISCHEMIA/HYPOXIA; PROLIFERATION AB Background and Purpose - Erythropoietin (EPO) has been well characterized and shown to improve functional outcomes after ischemic injury, but EPO may also have unexplored effects on neurovascular remodeling and neuronal replacement in the neonatal ischemic brain. The current study investigates the effects of exogenous administration of EPO on revascularization and neurogenesis, 2 major events thought to contribute to neuronal replacement, in the neonatal brain after hypoxia/ischemia (H/I). Methods - Seven-day-old rat pups were treated with recombinant human EPO or vehicle 20 minutes after H/I and again on postischemic days 2, 4, and 6. Rats were euthanized 7 or 28 days after H/I for evaluation of infarct volume, revascularization, neurogenesis, and neuronal replacement using bromodeoxyuridine incorporation, immunohistochemistry, and lectin labeling. Neurological function was assessed progressively for 28 days after H/I by gait testing, righting reflex and foot fault testing. Results - We demonstrate that exogenous EPO-enhanced revascularization in the ischemic hemisphere correlated with decreased infarct volume and improved neurological outcomes after H/I. In addition to vascular effects, EPO increased both neurogenesis in the subventricular zone and migration of neuronal progenitors into the ischemic cortex and striatum. A significant number of newly synthesized cells in the ischemic boundary expressed neuronal nuclei after EPO treatment, indicating that exogenous EPO led to neuronal replacement. Conclusions - Our data suggest that treatment with EPO contributes to neurovascular remodeling after H/I by promoting tissue protection, revascularization, and neurogenesis in neonatal H/I-injured brain, leading to improved neurobehavioral outcomes. C1 Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh, PA 15261 USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Vet Affairs Pittsburgh Hlth Care System, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Dept Neurol, Sch Med, 507 S Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15261 USA. EM chenj2@upmc.edu RI Liu, Jialing/A-8627-2012 OI Liu, Jialing/0000-0003-4420-4382 FU NINDS NIH HHS [NS051576, NS36736, NS43802, NS45048] NR 28 TC 92 Z9 102 U1 1 U2 5 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 2007 VL 38 IS 10 BP 2795 EP 2803 DI 10.1161/STROKEAHA.107.483008 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 213VJ UT WOS:000249694900029 PM 17702962 ER PT J AU Singhal, AB Ratai, E Benner, T Vangel, M Lee, V Koroshetz, WJ Schaefer, PW Sorensen, AG Gonzalez, RG AF Singhal, Aneesh B. Ratai, Eva Benner, Thomas Vangel, Mark Lee, Vallent Koroshetz, Walter J. Schaefer, Pamela W. Sorensen, A. Gregory Gonzalez, R. Gilberto TI Magnetic resonance Spectroscopy study of oxygen therapy in ischemic stroke SO STROKE LA English DT Article DE diffusion-weighted magnetic resonance imaging; neuroprotection; oxygen therapy; proton magnetic resonance spectroscopic imaging; stroke ID MR SPECTROSCOPY AB Background and Purpose - Recent studies suggest that normobaric oxygen therapy (NBO) is neuroprotective in acute ischemic stroke. Methods - We performed multivoxel magnetic resonance spectroscopic imaging and diffusion/perfusion MRI in patients with stroke treated with NBO or room air. Imaging was performed before, during, and after therapy. Results - Voxel-based analysis showed excellent correlation between apparent diffusion coefficient values, lactate, and N-acetyl-aspartate levels at all time points. Lactate decreased during NBO and increased post-NBO. N-acetyl-aspartate decreased in patients receiving room air but not in NBO-treated patients. Conclusion - These data suggest that NBO improves aerobic metabolism and preserves neuronal integrity in the ischemic brain. C1 Massachusetts Gen Hosp, J Philip Kistler MGH Stroke Res Ctr, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, J Philip Kistler MGH Stroke Res Ctr, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM asinghal@partners.org FU NINDS NIH HHS [AND R01 NS050041, R01 NS051412, R01 NS38477, P50 NS051343] NR 8 TC 43 Z9 47 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2007 VL 38 IS 10 BP 2851 EP 2854 DI 10.1161/STROKEAHA.107.487280 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 213VJ UT WOS:000249694900038 PM 17761914 ER PT J AU Chang, EY Minjarez, RC Kim, CY Seltman, AK Gopal, DV Diggs, B Davila, R Hunter, JG Jobe, BA AF Chang, E. Y. Minjarez, R. C. Kim, C. Y. Seltman, A. K. Gopal, D. V. Diggs, B. Davila, R. Hunter, J. G. Jobe, B. A. TI Endoscopic ultrasound for the evaluation of Nissen fundoplication integrity: a blinded comparison with conventional testing SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-American-Gastrointestinal-and-Endoscopic-Surgeons CY APR 28, 2006 CL Dallas, TX SP Soc Amer Gastrointestinal Endoscop Surg DE antireflux surgery; endoscopic ultrasound; failure; gastroesophageal reflux disease; Nissen fundoplication; reoperation ID LAPAROSCOPIC ANTIREFLUX SURGERY; FUNCLOPLICATION FAILS; INTEROBSERVER; MANAGEMENT; QUALITY; REFLUX; REDO AB Background: For patients whose symptoms develop after Nissen fundoplication, the precise mechanism of anatomic failure can be difficult to determine. The authors have previously reported the endosonographic hallmarks de. ning an intact Nissen fundoplication in swine and the known causes of failure. The current clinical trial tested the hypothesis that a defined set of endosonographic criteria can be applied to determine fundoplication integrity in humans. Methods: The study enrolled seven symptomatic and nine asymptomatic subjects at a mean of 6 years ( range, 1-30 years) after Nissen fundoplication. A validated gastroesophageal reflux disease (GERD)-specific questionnaire and medication history were completed. Before endoscopic ultrasound (EUS), all the patients underwent complete conventional testing ( upper endoscopy, esophagram, manometry, 24-h pH). A diagnosis was rendered on the basis of combined test results. Then EUS was performed by an observer blinded to symptoms, medication use, and conventional testing diagnoses. Because EUS and esophagogastro-duodenoscopy (EGD) are uniformly performed in combination, the EUS diagnosis was rendered on the basis of previously established criteria combined with the EGD interpretation. The diagnoses then were compared to examine the contribution of EUS in this setting. Results: The technique and defined criteria were easily applied to all subjects. All symptomatic patients had heartburn and were taking proton pump inhibitors (PPI). No asymptomatic patients were taking PPI. All diagnoses established with combined conventional testing were detected on EUS with upper endoscopy. Additionally, EUS resolved the etiology of a low lower esophageal sphincter pressure in two symptomatic patients and detected the additional diagnoses of slippage in two subjects. Among asymptomatic subjects, EUS identified additional diagnoses in two subjects considered to be normal by conventional testing methods. Conclusion: According to the findings, EUS is a feasible method for evaluating post-Nissen fundoplication hiatal anatomic relationships. The combination of EUS and EGD allows the mechanism of failure to be detected in patients presenting with postoperative symptoms after Nissen fundoplication. C1 Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. Univ Wisconsin, Div Gastroenterol, Madison, WI 53706 USA. Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. Portland VA Med Ctr, Surg Serv P3GS, Portland, OR 97207 USA. RP Jobe, BA (reprint author), Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. OI Diggs, Brian/0000-0003-3586-3757 FU NIDDK NIH HHS [K23 DK066165-02] NR 19 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD OCT PY 2007 VL 21 IS 10 BP 1719 EP 1725 DI 10.1007/s00464-007-9234-8 PG 7 WC Surgery SC Surgery GA 211XB UT WOS:000249555500007 PM 17345143 ER PT J AU Hess, R Bryce, CL Paone, S Fischer, G McTigue, KM Olshansky, E Zickmund, S Fitzgerald, K Siminerio, L AF Hess, Rachel Bryce, Cindy L. Paone, Suzanne Fischer, Gary McTigue, Kathleen M. Olshansky, Ellen Zickmund, Susan Fitzgerald, Katharine Siminerio, Linda TI Exploring challenges and Potentials of personal health records in diabetes self-management: Implementation and initial assessment SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Article ID CHRONIC CARE MODEL AB The University of Pittsburgh Medical Center (UPMC) has implemented a personal health record grounded in the Chronic Care Model, UPMC HealthTrak, to assist patients with diabetes self- management. UPMC HealthTrak is based in the physician office and connects the patient, physician, and electronic medical record (EMR). Its functionalities include secure, electronic communication with the physician's office, along with preventive healthcare reminders, and disease-specific tools and information. In this paper, we describe challenges to office-based implementation of and initial patient reaction to the technology in the context of diabetes care. UPMC has deployed a secure Web-based patient portal, UPMC HealthTrak. We implemented UPMC HealthTrak in the ambulatory setting and assessed its impact on patient - practice communication. We conducted 10 90-minute focus groups ( five pre- and five postimplementation) to assess patient reaction to UPMC HealthTrak. Focus groups were analyzed using grounded theory techniques. During the period September 2004-January 2007, there was no significant change in number of patient encounters or telephone calls received in our office, but the number of HealthTrak messages increased. Our 39 pre- and postimplementation focus group participants felt that the system would enhance communication with the office, and that the reminder system would be helpful. They also liked having access tolaboratory tests remotely. They were frustrated when tests were not released and messages not answered. A Web-based patient portal can be integrated into a clinical office, although patients may not quickly change communication patterns. Patients are responsive to technology. Future work should focus on diabetes-related outcomes assessment and intensifying interventions. C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15260 USA. Univ Phoenix, Phoenix, AZ USA. Univ Pittsburgh, Med Ctr, Informat Serv Dept, Pittsburgh, PA 15260 USA. Univ Calif Irvine, Program Nursing Sci, Irvine, CA 92717 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Inst Diabet, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15260 USA. RP Hess, R (reprint author), Ctr Res Hlth Care, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM hessr@upmc.edu OI Bryce, Cindy/0000-0001-6356-6675 FU NCRR NIH HHS [UL1 RR024153]; NIA NIH HHS [AG024254]; NIDDK NIH HHS [DK067192] NR 12 TC 54 Z9 54 U1 0 U2 15 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD OCT PY 2007 VL 13 IS 5 BP 509 EP 517 DI 10.1089/tmj.2006.0089 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 233JA UT WOS:000251086000020 PM 17999613 ER PT J AU Juppner, H AF Juppner, Harald TI Novel regulators of phosphate homeostasis and bone metabolism SO THERAPEUTIC APHERESIS AND DIALYSIS LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Japanese-Society-for-Kidney-Bone-Disease CY FEB 24, 2007 CL Tokyo, JAPAN SP Japanese Soc Kidney Bone Dis DE bone metabolism; dentin matrix protein; fibroblast growth factor-23; naPi-IIa; naPi-IIc; phosphate homeostasis ID HEREDITARY HYPOPHOSPHATEMIC RICKETS; FRIZZLED-RELATED PROTEIN-4; MATRIX EXTRACELLULAR PHOSPHOGLYCOPROTEIN; TUMOR-INDUCED OSTEOMALACIA; CHRONIC KIDNEY-DISEASE; OSTEOGLOPHONIC DYSPLASIA; LINKED HYPOPHOSPHATEMIA; ONCOGENIC OSTEOMALACIA; SERUM PHOSPHORUS; I COTRANSPORTER AB The regulation of phosphate homeostasis remains incompletely understood. Most insights into the underlying mechanisms were established by defining the molecular basis of different inherited disorders that are characterized by an abnormal regulation of phosphate homeostasis. Using this approach, three novel regulators were previously identified, namely PHEX ( a phosphate-regulating gene with homologies to endopeptidases on the X chromosome), fibroblast growth factor ( FGF)23 and UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). Other studies had revealed heterozygous mutations in the sodium phosphate co-transporter NaPi-IIa as the cause of hypophosphatemia associated with hypercalciuria and osteoporosis, and homozygous or compound heterozygous mutations in NaPi-IIc were shown to cause hereditary hypophosphatemic rickets with hypercalciuria. Recently, positional cloning approaches furthermore led to the identification of homozygous inactivating mutations in dentin matrix protein 1 (DMP1) as the cause of an autosomal recessive form of hypophosphatemia. Using different immunometric assays, intact and C-terminal FGF-23 levels were found to be elevated in patients with oncogenic osteomalacia, and the tumors responsible for this disease showed increased expression of FGF-23 mRNA. Intact and C-terminal FGF-23 levels are furthermore elevated in patients with X-linked hypophosphatemia. This disorder is caused by inactivating PHEX mutations suggesting that this endopeptidase is somehow, most likely indirectly, involved in the metabolism of intact FGF-23. FGF-23 levels were also found to be elevated in some patients with ARHP indicating that the lack of DMP1 up-regulates expression of this phosphaturic hormone. The concentration of C-terminal FGF-23, but not of intact FGF-23, is significantly elevated in two forms of tumoral calcinosis (TC). One form of TC is caused by homozygous inactivating GALNT3 mutations implying that the encoded enzyme, which is involved in the initiation of O-glycosylation, is important for preventing cleavage of FGF-23 into biologically inactive fragments. The second form of tumoral calcinosis is caused by different homozygous FGF-23 mutations that affect conserved serine residues that may undergo O-glycosylation by GALNT3; the lack of this post-translational modification leads to an abnormal processing of FGF-23 and increased secretion of C-terminal fragments. It remains unknown whether and how the different phosphate-regulating proteins interact with each other and it appears very likely that additional proteins are involved in this process. It also remains unclear whether the dramatically elevated FGF-23 levels in patients with different stages of chronic kidney disease affect bone metabolism, particularly the mineralization of newly formed osteoid. C1 Massachusetts Gen Hosp, Endocrine Unit & Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit & Pediat Nephrol Unit, 50 Blossum St, Boston, MA 02114 USA. EM hjueppner@partners.org NR 54 TC 15 Z9 15 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1744-9979 J9 THER APHER DIAL JI Ther. Apher. Dial. PD OCT PY 2007 VL 11 SU 1 BP S3 EP S22 DI 10.1111/j.1744-9987.2007.00513.x PG 20 WC Hematology; Urology & Nephrology SC Hematology; Urology & Nephrology GA 226FJ UT WOS:000250573000002 PM 17976082 ER PT J AU Jordan, AS Wellman, A Heinzer, RC Lo, YL Schory, K Dover, L Gautam, S Malhotra, A White, DP AF Jordan, Amy S. Wellman, Andrew Heinzer, Raphael C. Lo, Yu-Lun Schory, Karen Dover, Louise Gautam, Shiva Malhotra, Atul White, David P. TI Mechanisms used to restore ventilation after partial upper airway collapse during sleep in humans SO THORAX LA English DT Article ID GENIOGLOSSUS MUSCLE ACTIVATION; LUNG-VOLUME; NEGATIVE-PRESSURE; APNEA SYNDROME; NORMAL MEN; AROUSAL; COLLAPSIBILITY; PATHOGENESIS; STIMULI AB Background: Most patients with obstructive sleep apnoea (OSA) can restore airflow after an obstructive respiratory event without arousal at least some of the time. The mechanisms that enable this ventilatory recovery are unclear but probably include increased upper airway dilator muscle activity and/or changes in respiratory timing. The aims of this study were to compare the ability to recover ventilation and the mechanisms of compensation following a sudden reduction of continuous positive airway pressure ( CPAP) in subjects with and without OSA. Methods: Ten obese patients with OSA (mean (SD) apnoea-hypopnoea index 62.6 (12.4) events/h) and 15 healthy non-obese non-snorers were instrumented with intramuscular genioglossus electrodes and a mask/ pneumotachograph which was connected to a modified CPAP device that could deliver either continuous positive or negative pressure. During stable non-rapid eye movement sleep the CPAP was repeatedly reduced 2-10 cm H2O below the level required to eliminate flow limitation and was held at this level for 5 min or until arousal from sleep occurred. Results: During reduced CPAP the increases in genioglossus activity (311.5 (49.4)% of baseline in subjects with OSA and 315.4 (76.2)% of baseline in non-snorers, p = 0.9) and duty cycle (123.8 (3.9)% of baseline in subjects with OSA and 118.2 (2.8)% of baseline in non-snorers, p = 0.4) were similar in both groups, yet patients with OSA could restore ventilation without cortical arousal less often than non-snorers (54.1% vs 65.7% of pressure drops, p = 0.04). When ventilatory recovery did not occur, genioglossus muscle and respiratory timing changes still occurred but these did not yield adequate pharyngeal patency/ ventilation. Conclusions: Compensatory mechanisms (increased genioglossus muscle activity and/or duty cycle) often restore ventilation during sleep but may be less effective in obese patients with OSA than in non-snorers. C1 Brigham & Womens Hosp, Sleep Disorders Res Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Gen Clin Res Ctr, Boston, MA 02215 USA. RP Jordan, AS (reprint author), BIDMC, Sleep Disorders Program, 75 Francis St, Boston, MA 02115 USA. EM ajordan@rics.bwh.harvard.edu OI Jordan, Amy/0000-0001-8561-9766 FU NCRR NIH HHS [M01 RR001032, M01 RR01032]; NHLBI NIH HHS [HL73146-01, P50 HL060292, P50 HL60292, R01 HL073146, R01 HL073146-03]; NIA NIH HHS [AG024837-01, K23 AG024837, K23 AG024837-04] NR 29 TC 52 Z9 53 U1 0 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD OCT PY 2007 VL 62 IS 10 BP 861 EP 867 DI 10.1136/thx.2006.070300 PG 7 WC Respiratory System SC Respiratory System GA 216HE UT WOS:000249868300007 PM 17412778 ER PT J AU Dole, VS Bergmeier, W Patten, IS Hirahashi, J Mayadas, TN Wagner, DD AF Dole, Vandana S. Bergmeier, Wolfgang Patten, Ian S. Hirahashi, Junichi Mayadas, Tanya N. Wagner, Denisa D. TI PSGL-I regulates platelet P-selectin-mediated endothelial activation and shedding of P-selectin from activated platelets SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE PSGL-I; P-selectin; shedding; platelets; endothelial-activation ID CORONARY-ARTERY-DISEASE; GLYCOPROTEIN LIGAND-1; NEUTROPHIL ELASTASE; VIVO; ADHESION; HEMOSTASIS; EXPRESSION; BINDING; MICE; CD11B/CD18 AB We have previously shown that activated platelets in circulation stimulate release of endothelial Weibel-Palade bodies thus increasing leukocyte rolling in venules. P-selectin on the activated platelets mediates adhesion to leukocytes via PSGL-1 and is rapidly shed into plasma. We were interested in studying the role of PSGL-1 in regulating expression and function of platelet P-selectin. We show here that PSGL-1 is critical for the activation of endothelial cells in venules of mice infused with activated platelets. The interaction of platelet P-selectin with PSGL-1 is also required for P-selectin shedding, as P-selectin was retained significantly longer on the surface of activated platelets infused into PSGL-1(-/-) compared to wild-type mice. The leukocyte integrin (alpha M beta 2 (Mac-1) was not required for P-selectin shedding. In addition to shedding, P-selectin can be downregulated from the platelet surface through internalization and this is the predominant mechanism in the absence of PSGL-1. We demonstrate that leukocyte-neutrophil elastase, known to cleave P-selectin in vitro, is not the major sheddase for P-selectin in vivo. In conclusion, interaction of platelet P-selectin with PSGL-1 is crucial for activation of the endothelium and Weibel-Palade body secretion. The interaction with PSGL-1 also results in rapid shedding of P-selectin thus downregulating the inflammatory potential of the platelet. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu FU NHLBI NIH HHS [R37 HL041002] NR 45 TC 38 Z9 39 U1 0 U2 5 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD OCT PY 2007 VL 98 IS 4 BP 806 EP 812 DI 10.1160/TH07-03-0207 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 220DO UT WOS:000250137300017 PM 17938805 ER PT J AU Parekkadan, B Sethu, P Van Poll, D Yarmush, ML Toner, M AF Parekkadan, Biju Sethu, Palaniappan Van Poll, Daan Yarmush, Martin L. Toner, Mehmet TI Osmotic selection of human mesenchymal stem/progenitor cells from umbilical cord blood SO TISSUE ENGINEERING LA English DT Article ID STEM-CELLS; BONE-MARROW; VOLUME REGULATION AB The isolation of undifferentiated adult stem/progenitor cells remains a challenging task primarily due to the rare quantity of these cells in biological samples and the lack of unique markers. Herein, we report a relatively straightforward method for isolation of human mesenchymal stem cells (MSCs) based on their unusual resistance to osmotic lysis, which we term "osmotic selection" (OS). MSCs can remarkably withstand significant exposure to hypotonic conditions (> 30min) with only a reversible impairment in cell proliferation and with no loss of stem cell potential after exposure. Comparison of MSCs to other circulating nonhematopoietic cells revealed a time regime, by which purification of these cells would be attainable without considerable cell loss. OS showed a 50-fold enrichment of fibroblast colony-forming units from umbilical cord blood samples when compared to commonly employed techniques. After upstream processing, isolated cells using OS were immunophenotyped to be CD14-, CD34-, CD45-, CD44+, CD105+, and CD106+, and displayed multipotent differentiation. Preliminary investigations to determine mechanisms responsible for osmolytic resistance revealed MSCs to have an ineffective volume of 59%, with the ability to double cell volume at infinite dilution. Disruption of filamentous actin polymerization by cytochalasin D sensitized MSCs to osmotic lysis, which suggests a cytoskeletal element involved in osmolytic resistance. C1 Univ Louisville, Dept Biomed Engn, Louisville, KY USA. Harvard Med Sch, Massachusetts Gen Hosp, Shriners Hosp Children, BioMEMS Resource Ctr,Ctr Engn Med & Surg Serv, Boston, MA USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. RP Toner, M (reprint author), Univ Louisville, Dept Biomed Engn, Louisville, KY USA. EM mtoner@hms.harvard.edu FU NIBIB NIH HHS [P41 EB002503] NR 17 TC 21 Z9 24 U1 5 U2 16 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD OCT PY 2007 VL 13 IS 10 BP 2465 EP 2474 DI 10.1089/ten.2007.0054 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA 220NE UT WOS:000250162600009 PM 17665999 ER PT J AU Valeri, CR Khuri, S Ragno, G AF Valeri, C. Robert Khuri, Shukri Ragno, Gina TI Nonsurgical bleeding diathesis in anemic thrombocytopenic patients: role of temperature, red blood cells, platelets, and plasma-clotting proteins SO TRANSFUSION LA English DT Review ID OPEN-HEART-SURGERY; RECOMBINANT-HUMAN-ERYTHROPOIETIN; CRYOPRESERVED BABOON PLATELETS; FREEZING HUMAN PLATELETS; CHRONIC KIDNEY-DISEASE; FRESH-FROZEN PLASMA; CARDIOPULMONARY BYPASS; NITRIC-OXIDE; EXTRACORPOREAL-CIRCULATION; WHOLE-BLOOD AB Research at the Naval Blood Research Laboratory (Boston, MA) for the past four decades has focused on the preservation of red blood cells (RBCs), platelets (PLTs), and plasma-clotting proteins to treat wounded servicemen suffering blood loss. We have studied the survival and function of fresh and preserved RBCs and PLTs and the function of fresh and frozen plasma-clotting proteins. This report summarizes our peer-reviewed publications on the effects of temperature, RBCs, PLTs, and plasma-clotting proteins on the bleeding time (BT) and nonsurgical blood loss. The term nonsurgical blood loss refers to generalized, systemic bleeding that is not corrected by surgical interventions. We observed that the BT correlated with the volume of shed blood collected at the BT site and to the nonsurgical blood loss in anemic thrombocytopenic patients after cardiopulmonary bypass surgery. Many factors influence the BT, including temperature; hematocrit (Hct); PLT count; PLT size; PLT function; and the plasma-clotting proteins factor (F)VIII, von Willebrand factor, and fibrinogen level. Our laboratory has studied temperature, Hct, PLT count, PLT size, and PLT function in studies performed in non-aspirin-treated and aspirin-treated volunteers, in aspirin-treated baboons, and in anemic thrombocytopenic patients. This monograph discusses the role of RBCs and PLTs in the restoration of hemostasis, in the hope that a better understanding of the hemostatic mechanism might improve the treatment of anemic thrombocytopenic patients. Data from our studies have demonstrated that it is important to transfuse anemic thrombocytopenic patients with RBCs that have satisfactory viability and function to achieve a Hct level of 35 vol percent before transfusing viable and functional PLTs. The Biomedical Excellence for Safer Transfusion (BEST) Collaborative recommends that preserved PLTs have an in vivo recovery of 66 percent of that of fresh PLTs and a life span that is at least 50 percent that of fresh PLTs. Their recommendation does not include any indication that preserved PLTs must be able to function to reduce the BT and reduce or prevent nonsurgical blood loss. One of the hemostatic effects of RBC is to scavenge endothelial cell nitric oxide, a vasodilating agent that inhibits PLT function. In addition, endothelin may be released from endothelial cells, a potent vasoconstrictor substance,to reduce blood flow at the BT site. RBCs, like PLTs at the BT site, may provide arachidonic acid and adenosine diphosphate to stimulate the PLTs to make thromboxane, another potent vasoconstrictor substance and a PLT-aggregating substance. At the BT site, the PLTs and RBCs are activated and phosphatidyl serine is exposed on both the PLTs and the RBCs. FVa and FXa, which generate prothrombinase activity to produce thrombin, accumulate on the PLTs and RBCs. A Hct level of 35 vol percent at the BT site minimizes shear stress and reduces nitric oxide produced by endothelial cells. The transfusion trigger for prophylactic PLT transfusion should consider both the Hct and the PLT count. The transfusion of RBCs that are both viable and functional to anemic thrombocytopenic patients may reduce the need for prophylactic leukoreduced PLTs, the alloimmunization of the patients, and the associated adverse events related to transfusion-related acute lung injury. The cost for RBC transfusions will be significantly less than the cost for the prophylactic PLT transfusions. C1 NBRL Inc, Boston, MA USA. Boston VA Healthcare Syst, Boston, MA USA. RP Valeri, CR (reprint author), Naval Blood Res Lab Inc, 195 Bournehurst Dr, Plymouth, MA 02360 USA. EM navblood@nbrl.org NR 208 TC 40 Z9 40 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2007 VL 47 IS 4 SU S BP 206S EP 248S DI 10.1111/j.1537-2995.2007.01465.x PG 43 WC Hematology SC Hematology GA 217NJ UT WOS:000249954300002 PM 17888061 ER PT J AU Dzik, WH AF Dzik, W. H. TI The James Blundell Award Lecture 2006: transfusion and the treatment of haemorrhage: past, present and future SO TRANSFUSION MEDICINE LA English DT Review DE fresh frozen plasma; genetics; genomics; history; James Blundell; pharmocogenetics ID FRESH-FROZEN PLASMA; COAGULATION AB In the early years of the 19th century, James Blundell reported in the Lancet the first clinical application of blood transfusion for the treatment of haemorrhage. Although these initial experiments may appear to us to have burst upon the medical world, Blundell had in fact done a decade of pre clinical research using animal models to establish principles to be brought to the clinic. His pivotal pre clinical experiments and the insights he gained are described in detail. Today, blood transfusion remains the cornerstone of treatment for serious bleeding - not only to restore oxygen carrying capacity but also to improve haemostasis, arrest and prevent bleeding. However, the indications for the use of blood components to treat bleeding remain ill-defined. In particular, despite the enormous volumes of fresh frozen plasma (FFP) transfused worldwide, the evidence that commonly used coagulation tests are reliable guides to transfusion with FFP is scant. Recent laboratory and clinical studies provide insight into the weaknesses of current coagulation tests as a guide to blood management. In the future, the application of genomics to haemostasis will uncover genetic polymorphisms leading to improved diagnostics and more tailored medical therapeutics. Examples of the emerging use of clinical genomics are presented. Ultimately, the application of widescale genomics testing will refresh our understanding of human physiology and will reassert the importance of the individual in patient care. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, J-224,55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org NR 19 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0958-7578 J9 TRANSFUSION MED JI Transfus. Med. PD OCT PY 2007 VL 17 IS 5 BP 367 EP 374 DI 10.1111/j.1365-3148.2007.00795.x PG 8 WC Hematology SC Hematology GA 215SD UT WOS:000249828400004 PM 17903138 ER PT J AU Schmidt-Supprian, M Wunderlich, FT Rajewsky, K AF Schmidt-Supprian, Marc Wunderlich, F. Thomas Rajewsky, Klaus TI Excision of the Frt-flanked neo(R) supercript stop cassette from the CD19cre knock-in transgene reduces Cre-mediated recombination SO TRANSGENIC RESEARCH LA English DT Article DE CD19cre mouse stain; conditional gene targeting efficiency; B cells; Frt-site flanked neomycin resistance gene cassette ID B-CELLS; MICE; MUTAGENESIS; MUTATION AB Intercross of mice transgenic for Flp-recombinase with the CD19cre mouse strain leads to excision of the Frt-flanked neo(R)cassette from the CD19cre knock-in transgene. This significantly reduces the expression level of Cre by the CD19cre transgene and consequently decreases the extent of Cre-mediated recombination of loxP-flanked alleles, most likely due to the fact that this neo(R) cassette contains polyoma enhancer sequences. We wish to draw attention to this finding, since the Flp-deleter mouse strain is commonly used to remove Frt-flanked selection cassettes in vivo from conditional alleles. Therefore conditional alleles have to be separated from the Flp-deleter transgene by breeding before crosses with CD19cre mice are initiated. In addition our findings suggest that gene expression from the CD19 locus can be increased by the insertion of exogenous enhancer sequences, without compromising B cell specificity. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Cologne, Genet Inst, D-50674 Cologne, Germany. RP Schmidt-Supprian, M (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM supprian@cbr.med.harvard.edu RI Schmidt-Supprian, Marc/F-5893-2011 OI Schmidt-Supprian, Marc/0000-0002-8543-6166 FU NIAID NIH HHS [AI057947] NR 11 TC 10 Z9 12 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD OCT PY 2007 VL 16 IS 5 BP 657 EP 660 DI 10.1007/s11248-007-9100-4 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 207ST UT WOS:000249272100010 PM 17541717 ER PT J AU Barry, M Perner, S Demichelis, F Rubin, MA AF Barry, Marc Perner, Sven Demichelis, Francesca Rubin, Mark A. TI TMPRSS2-ERG fusion heterogeneity in Multifocal prostate cancer: Clinical and biologic implications SO UROLOGY LA English DT Article ID FEATURES AB OBJECTIVES To characterize the clonality of TMPRSS2-ERG fusion in multifocal prostate cancer. METHODS From 80 consecutive radical prostatectomy specimens, we identified 32 cases with multiple spatially separate tumors. In each case, we assessed two to three tumor foci for TMPRSS2-ERG fusion using an ERG break-apart interphase fluorescence in situ hybridization assay. RESULTS Individual tumor foci showed homogenity for fusion status (intrafocal clonal homogenity). In 19 (59%) of the 32 cases, all foci within a case had the same fusion status (interfocal homogeneity). In 15 (80%) of the 19 cases, no foci had fusion, and in 4 (20%), all foci had fusion. Of the 32 cased, 13 (41%) demonstrated heterogeneity for fusion status within a case (interfocal clonal heterogeneity). CONCLUSIONS In this study, we have demonstrated interfocal heterogeneity and intrafocal homogeneity for TMPRSS2-ERG fusion in prostate cancer with multiple tumors. These findings support the multiclonal nature of prostate cancer with clinical implications for needle biopsy strategies and the development of urine-based screening tests. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Ulm, Dept Pathol, Ulm, Germany. ITC irst, SRA Div, Bioinformat Grp, Povo, Trento, Italy. MIT, Broad Inst, Cambridge, MA 02139 USA. Dana Farber Harvard Comprehens Canc Ctr, Boston, MA USA. RP Rubin, MA (reprint author), Weill Cornel Med Coll, 1300 York Ave,Room C 410-A, New York, NY USA. EM rubinma@med.cornell.edu OI Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 FU NCI NIH HHS [P50 CA090381]; NIA NIH HHS [R01AG21404, R01 AG021404] NR 14 TC 103 Z9 105 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD OCT PY 2007 VL 70 IS 4 BP 630 EP 633 DI 10.1016/j.urology.2007.08.032 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 234FF UT WOS:000251145400002 PM 17991527 ER PT J AU Li, X Song, BW Xiang, SH Sodroski, J AF Li, Xing Song, Byeongwoon Xiang, Shi-hua Sodroski, Joseph TI Functional interplay between the B-box 2 and the B30.2(SPRY) domains of TRIM5 alpha SO VIROLOGY LA English DT Article DE retrovirus; restriction factor; TRIMCyp; cyclophilin; trimer; B-box 2; B30.2(SPRY); HIV-1; N-MLV ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; RESTRICTION FACTOR; CYCLOPHILIN-A; TRIPARTITE MOTIF; MONKEY TRIM5-ALPHA; CYTOPLASMIC BODIES; UBIQUITIN LIGASE; HIV-1 INFECTION; CAPSID-BINDING AB The retroviral restriction factors, TRIM5 alpha and TRIMCyp, consist of RING and 13-box 2 domains separated by a coiled coil from carboxyterminal domains. These carboxy-terminal domains (the B30.2(SPRY) domain in TRIM alpha(x and the cyclophilin A domain in TRIMCyp) recognize the retroviral capsid. Here we show that some B-box 2 changes in TRIM5 alpha(y, but not in TRIMCyp, resulted in decreased human immunodeficiency virus (HIV-1) capsid binding. The phenotypic effects of these 13-box 2 changes on the restriction of retroviral infection depended on the potency of restriction and the affinity of the TRIM5a interaction with the viral capsid, two properties specified by the B30.2(SPRY) domain. Thus, some alterations in the TRIM5 alpha 13-box 2 domain apparently affect the orientation or conformation of the B30.2(SPRY) domain, influencing capsid recognition. (C) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, 44 Binney Str, JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009 FU NIAID NIH HHS [R01 AI063987-03, R01 AI063987, AI06354, AI063987, R21 AI076094, R21 AI076094-01] NR 49 TC 22 Z9 25 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 30 PY 2007 VL 366 IS 2 BP 234 EP 244 DI 10.1016/j.rirol.2007.04.022 PG 11 WC Virology SC Virology GA 214WR UT WOS:000249769400002 PM 17543365 ER PT J AU Lu, HAJ Sun, TX Matsuzaki, T Yi, XH Eswara, J Bouley, R Mckee, M Brown, D AF Lu, Hua A. J. Sun, Tian-Xiao Matsuzaki, Toshiyuki Yi, Xian-Hua Eswara, Jairam Bouley, Richard Mckee, Mary Brown, Dennis TI Heat shock protein 70 interacts with aquaporin-2 and regulates its trafficking SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; RENAL EPITHELIAL-CELLS; KIDNEY COLLECTING DUCT; WATER CHANNEL; MOLECULAR CHAPERONE; COATED PITS; RAT-KIDNEY; INTRACELLULAR VESICLES; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE AB The trafficking of aquaporin-2 (AQP2) involves multiple complex pathways, including regulated, cAMP-, and cGMP-mediated pathways, as well as a constitutive recycling pathway. Although several accessory proteins have been indirectly implicated in AQP2 recycling, the direct protein-protein interactions that regulate this process remain largely unknown. Using yeast two-hybrid screening of a human kidney cDNA library, we have identified the 70-kDa heat shock proteins as AQP2-interacting proteins. Interaction was confirmed by mass spectrometry of proteins pulled down from rat kidney papilla extract using a GST-AQP2 C-terminal fusion protein (GST-A2C) as a bait, by co-immunoprecipitation (IP) assays, and by direct binding assays using purified hsc70 and the GST-A2C. The direct interaction of AQP2 with hsc70 is partially inhibited by ATP, and the Ser-256 residue in the AQP2 C terminus is important for this direct interaction. Vasopressin stimulation in cells enhances the interaction of hsc70 with AQP2 in IP assays, and vasopressin stimulation in vivo induces an increased co-localization of hsc70 and AQP2 on the apical membrane of principal cells in rat kidney collecting ducts. Functional knockdown of hsc70 activity in AQP2 expressing cells results in membrane accumulation of AQP2 and reduced endocytosis of rhodaminetransferrin. Our data also show that AQP2 interacts with hsp70 in multiple in vitro binding assays. Finally, in addition to hsc70 and hsp70, AQP2 interacts with several other key components of the endocytotic machinery in co-IP assays, including clathrin, dynamin, and AP2. To summarize, we have identified the 70-kDa heat shock proteins as a AQP2 interactors and have shown for hsc70 that this interaction is involved in AQP2 trafficking. C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. EM brown@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK43351, DK075940, DK38452, DK57521] NR 58 TC 64 Z9 69 U1 0 U2 5 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 28 PY 2007 VL 282 IS 39 BP 28721 EP 28732 DI 10.1074/jbc.M611101200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 213BY UT WOS:000249642100046 PM 17636261 ER PT J AU Huang, CC Lam, SN Acharya, P Tang, M Xiang, SH Hussan, SSU Stanfield, RL Robinson, J Sodroski, J Wilson, IA Wyatt, R Bewley, CA Kwong, PD AF Huang, Chih-chin Lam, Son N. Acharya, Priyamvada Tang, Min Xiang, Shi-Hua Hussan, Syed Shahzad-ul Stanfield, Robyn L. Robinson, James Sodroski, Joseph Wilson, Ian A. Wyatt, Richard Bewley, Carole A. Kwong, Peter D. TI Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4 SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; CORECEPTOR; BINDING; RECEPTORS; ENTRY; V3; DETERMINANTS; DOMAINS; REGION AB The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (alpha-helix) and 412d (extended-loop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA. RP Bewley, CA (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov; pdkwong@nih.gov FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [U19 AI067854-03, P30 AI060354, U19 AI067854] NR 28 TC 268 Z9 276 U1 4 U2 39 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 28 PY 2007 VL 317 IS 5846 BP 1930 EP 1934 DI 10.1126/science.1145373 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214US UT WOS:000249764300042 PM 17901336 ER PT J AU Xie, HF Orkin, SH AF Xie, Huafeng Orkin, Stuart H. TI Immunology - Changed destiny SO NATURE LA English DT Editorial Material ID CELL PROGENITORS; STEM-CELLS; B-CELLS; MACROPHAGES; LINEAGES C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Xie, HF (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu NR 12 TC 9 Z9 9 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 27 PY 2007 VL 449 IS 7161 BP 410 EP 411 DI 10.1038/449410a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214GQ UT WOS:000249724800027 PM 17898754 ER PT J AU Yan, CT Boboila, C Souza, EK Franco, S Hickernell, TR Murphy, M Gumaste, S Geyer, M Zarrin, AA Manis, JP Rajewsky, K Alt, FW AF Yan, Catherine T. Boboila, Cristian Souza, Ellen Kris Franco, Sonia Hickernell, Thomas R. Murphy, Michael Gumaste, Sunil Geyer, Mark Zarrin, Ali A. Manis, John P. Rajewsky, Klaus Alt, Frederick W. TI IgH class switching and translocations use a robust non-classical end-joining pathway SO NATURE LA English DT Article ID DOUBLE-STRAND BREAK; DNA-LIGASE-IV; MAMMALIAN-CELLS; V(D)J RECOMBINATION; REPAIR; XRCC4; MICE; LYMPHOCYTES; PROTEINS; REGIONS AB Immunoglobulin variable region exons are assembled in developing B cells by V(D)J recombination. Once mature, these cells undergo class-switch recombination (CSR) when activated by antigen. CSR changes the heavy chain constant region exons (CH) expressed with a given variable region exon from Cm to a downstream CH (for example, C gamma, C epsilon or C alpha), thereby switching expression from IgM to IgG, IgE or IgA. Both V(D)J recombination and CSR involve the introduction of DNA double-strand breaks and their repair by means of end joining(1,2). For CSR, double-strand breaks are introduced into switch regions that flank Cm and a downstream CH, followed by fusion of the broken switch regions(1). In mammalian cells, the 'classical' non-homologous end joining (C-NHEJ) pathway repairs both general DNA double-strand breaks and programmed double-strand breaks generated by V(D)J recombination(2,3). C-NHEJ, as observed during V(D)J recombination, joins ends that lack homology to form 'direct' joins, and also joins ends with several base-pair homologies to form microhomology joins(3,4). CSR joins also display direct and microhomology joins, and CSR has been suggested to use C-NHEJ(5-8). Xrcc4 and DNA ligase IV (Lig4), which cooperatively catalyse the ligation step of C-NHEJ, are the most specific C-NHEJ factors; they are absolutely required for V(D)J recombination and have no known functions other than C-NHEJ(2). Here we assess whether C-NHEJ is also critical for CSR by assaying CSR in Xrcc4- or Lig4-deficient mouse B cells. C-NHEJ indeed catalyses CSR joins, because C-NHEJ-deficient B cells had decreased CSR and substantial levels of IgH locus (immunoglobulin heavy chain, encoded by Igh) chromosomal breaks. However, an alternative end-joining pathway, which is markedly biased towards microhomology joins, supports CSR at unexpectedly robust levels in C-NHEJ-deficient B cells. In the absence of C-NHEJ, this alternative end-joining pathway also frequently joins Igh locus breaks to other chromosomes to generate translocations. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu OI Geyer, Mark/0000-0001-5248-9117 FU NCI NIH HHS [P01 CA092625] NR 31 TC 329 Z9 335 U1 0 U2 14 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 27 PY 2007 VL 449 IS 7161 BP 478 EP U9 DI 10.1038/nature06020 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214GQ UT WOS:000249724800044 PM 17713479 ER PT J AU Meijers, R Puettmann-Holgado, R Skiniotis, G Liu, JH Walz, T Wang, JH Schmucker, D AF Meijers, Rob Puettmann-Holgado, Roland Skiniotis, Georgios Liu, Jin-Huan Walz, Thomas Wang, Jia-Huai Schmucker, Dietmar TI Structural basis of Dscam isoform specificity SO NATURE LA English DT Article ID DROSOPHILA DSCAM; CELL-ADHESION; AXON GUIDANCE; MOLECULAR DIVERSITY; PROTEIN RECOGNITION; SURFACE-RECEPTORS; CRYSTAL-STRUCTURE; SELF-AVOIDANCE; REFINEMENT; HORSESHOE AB The Dscam gene gives rise to thousands of diverse cell surface receptors(1) thought to provide homophilic and heterophilic recognition specificity for neuronal wiring(2-4) and immune responses(5). Mutually exclusive splicing allows for the generation of sequence variability in three immunoglobulin ecto-domains, D2, D3 and D7. We report X-ray structures of the amino-terminal four immunoglobulin domains (D1-D4) of two distinct Dscam isoforms. The structures reveal a horseshoe configuration, with variable residues of D2 and D3 constituting two independent surface epitopes on either side of the receptor. Both isoforms engage in homo-dimerization coupling variable domain D2 with D2, and D3 with D3. These interactions involve symmetric, antiparallel pairing of identical peptide segments from epitope I that are unique to each isoform. Structure-guided mutagenesis and swapping of peptide segments confirm that epitope I, but not epitope II, confers homophilic binding specificity of full-length Dscam receptors. Phylogenetic analysis shows strong selection of matching peptide sequences only for epitope I. We propose that peptide complementarity of variable residues in epitope I of Dscam is essential for homophilic binding specificity. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Univ Freiburg, Inst Biol 3, D-79104 Freiburg, Germany. RP Wang, JH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM jwang@red.dfci.harvard.edu; dietmar_schmucker@dfci.harvard.edu RI Meijers, Rob/D-5521-2011; OI Meijers, Rob/0000-0003-2872-6279 NR 33 TC 90 Z9 92 U1 2 U2 9 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 27 PY 2007 VL 449 IS 7161 BP 487 EP U12 DI 10.1038/nature06147 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214GQ UT WOS:000249724800046 PM 17721508 ER PT J AU Treadway, K AF Treadway, Katharine TI The code SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Treadway, K (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 27 PY 2007 VL 357 IS 13 BP 1273 EP 1275 DI 10.1056/NEJMp078115 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 214BR UT WOS:000249711500001 PM 17898094 ER PT J AU Avram, MM Gobel, V Sepehr, A Buzney, EA AF Avram, Mathew M. Gobel, Verena Sepehr, Alireza Buzney, Elizabeth A. TI Case 30-2007: A newborn girl with skin lesions - Cutaneous Langerhans'-cell histiocytosis, with single-organ-system involvement SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SIMPLEX-VIRUS-INFECTIONS; SELF-HEALING RETICULOHISTIOCYTOSIS; HASHIMOTO-PRITZKER; MANAGEMENT; PREGNANCY; VARICELLA; CHILDREN; PERIOD; ZOSTER C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Avram, MM (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. NR 26 TC 4 Z9 4 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 27 PY 2007 VL 357 IS 13 BP 1327 EP 1335 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 214BR UT WOS:000249711500011 PM 17898103 ER PT J AU Halpern, SD Ubel, PA Asch, DA AF Halpern, Scott D. Ubel, Peter A. Asch, David A. TI Harnessing the power of default options to improve health care SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACUTE LUNG INJURY; CRITICALLY-ILL PATIENTS; MECHANICAL VENTILATION; RECOMMENDATIONS; PATERNALISM; DECISIONS; PNEUMONIA; CHOICE C1 Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Dept Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Vet Affairs Med Ctr, Dept Med, Ann Arbor, MI USA. Univ Michigan, Ctr Behav & Decis Sci Med, Ann Arbor, MI 48109 USA. RP Halpern, SD (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, 711 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM scott.halpern@uphs.upenn.edu NR 30 TC 103 Z9 104 U1 1 U2 10 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 27 PY 2007 VL 357 IS 13 BP 1340 EP 1344 DI 10.1056/NEJMsb071595 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 214BR UT WOS:000249711500013 PM 17898105 ER PT J AU Zhu, MJ Ou, WB Fletcher, CDM Cohen, P Demetri, GD Fletcher, JA AF Zhu, M-J Ou, W-B Fletcher, C. D. M. Cohen, P. S. Demetri, G. D. Fletcher, J. A. TI KIT oncoprotein interactions in gastrointestinal stromal tumors: therapeutic relevance SO ONCOGENE LA English DT Article DE KIT; PDGFRA; kinase; interaction; signal transduction ID OF-FUNCTION MUTATIONS; C-KIT; IMATINIB MESYLATE; ACTIVATION; CELL; KINASE; SURVIVAL; PROLIFERATION; MECHANISMS; INHIBITOR AB Most gastrointestinal stromal tumors (GISTs) express oncogenic and constitutively active forms of the KIT or platelet-derived growth factor receptor alpha (PDGFRA) receptor tyrosine kinase proteins, and these kinase oncoproteins serve as targets for effective therapies. Given that mutant KIT oncoproteins serve crucial transforming roles in GISTs, we evaluated interactions with the KIT oncoproteins and determined signaling pathways that are dependent on KIT oncogenic activation in GISTs. Tyrosine-phosphorylated KIT oncoproteins interacted with PDGFRA, PDGFRB, phosphatidylinositol 3-kinase (PI3-K) and PKC theta in GIST cells, and these interactions were abolished by KIT inhibition with imatinib or PKC412 or KIT RNAi. Notably, tyrosine-phosphorylated PDGFRA was prominent in frozen GIST tumors expressing KIT oncoproteins, suggesting that KIT-mediated PDGFRA phosphorylation is an efficient and biologically consequential mechanism in GISTs. Activated signaling intermediates were identified by immuno affinity purification of tyrosine-phosphorylated proteins in GIST cells before and after treatment with KIT inhibitors, and these analyses show that GRB2, SHC, CBL and MAPK activation are largely KIT dependent in GISTs, whereas PI3-K, STAT1 and STAT3 activation are partially KIT dependent. In addition, we found that phosphorylation of several tyrosine kinase proteinsincluding JAK1 and EPHA4 -did not depend on KIT activation. Likewise, paxillin activation was independent of the KIT oncogenic signal. These studies identify signaling pathways that can provide both KIT-dependent and KIT-independent therapeutic synergies in GIST, and thereby highlight clinical strategies that might consolidate GIST therapeutic response to KIT/PDGFRA inhibition. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Novartis Oncol, Florham Pk, NJ USA. Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. RP Zhu, MJ (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM mzhu2@partners.org NR 22 TC 31 Z9 32 U1 0 U2 0 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 27 PY 2007 VL 26 IS 44 BP 6386 EP 6395 DI 10.1038/sj.onc.1210464 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 214KY UT WOS:000249737600003 PM 17452978 ER PT J AU McBryan, J Howlin, J Kenny, PA Shioda, T Martin, F AF McBryan, J. Howlin, J. Kenny, P. A. Shioda, T. Martin, F. TI ER alpha-CITED1 co-regulated genes expressed during pubertal mammary gland development: implications for breast cancer prognosis SO ONCOGENE LA English DT Article DE mammary gland; puberty; development; CITEDI; ER alpha ID DUCTAL MORPHOGENESIS; BRANCHING MORPHOGENESIS; EPITHELIAL-CELLS; IN-VIVO; GROWTH; CITED1; TRANSCRIPTION; PROTEINS; REVEALS; DIFFERENTIATION AB Expression microarray analysis identified over 930 genes regulated during puberty in the mouse mammary gland. Most prominent were genes whose expression increased in parallel with pubertal development and remained high thereafter. Members of the Wnt, transforming growth factor-beta and oestrogen-signalling pathways were significantly overrepresented. Comparison to expression data from CITED1 knockout mice identified a subset of oestrogen-responsive genes displaying altered expression in the absence of CITED1. Included in this subset are stanniocalcin2 (Stc2) and amphiregulin (Areg). Chromatin immunoprecipitation revealed that ER alpha binds to oestrogen response elements in both the Stc2 and Areg genes in the mammary gland during puberty. Additionally, CITED1 and ER alpha localize to the same epithelial cells of the pubertal mammary gland, supporting a role for interaction of these two proteins during normal development. In a human breast cancer data set, expression of Stc2, Areg and CITED1 parallel that of ER alpha. Similar to ERa, CITED1 expression correlates with good outcome in breast cancer, implying that potential maintenance of the ER alpha-CITED1 co-regulated signalling pathwayin breast tumours can indicate good prognosis. C1 Univ Coll Dublin, Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin 4, Ireland. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. Massachusetts Gen Hosp, Ctr Canc, Lab Tumour Biol, Charlestown, MA USA. RP Martin, F (reprint author), Univ Coll Dublin, Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin 4, Ireland. EM finian.martin@ucd.ie RI Kenny, Paraic/A-3120-2008; Howlin, Jill /G-9665-2011; OI Howlin, Jill /0000-0002-2766-3002; McBryan, Jean/0000-0002-7568-2208 NR 45 TC 32 Z9 32 U1 0 U2 1 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 27 PY 2007 VL 26 IS 44 BP 6406 EP 6419 DI 10.1038/sj.onc.1210468 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 214KY UT WOS:000249737600005 PM 17486082 ER PT J AU Gold, MC Robinson, TL Cook, MS Byrd, LK Ehlinger, HD Lewinsohn, DM Lewinsohn, DA AF Gold, Marielle C. Robinson, Tammie L. Cook, Matthew S. Byrd, Laura K. Ehlinger, Heather D. Lewinsohn, David M. Lewinsohn, Deborah A. TI Human Neonatal Dendritic Cells Are Competent in MHC Class I Antigen Processing and Presentation SO PLOS ONE LA English DT Article AB Neonates are clearly more susceptible to severe disease following infection with a variety of pathogens than are adults. However, the causes for this are unclear and are often attributed to immunological immaturity. While several aspects of immunity differ between adults and neonates, the capacity of dendritic cells in neonates to process and present antigen to CD8(+) T cells remains to be addressed. We used human CD8(+) T cell clones to compare the ability of neonatal and adult monocyte-derived dendritic cells to present or process and present antigen using the MHC class I pathway. Specifically, we assessed the ability of dendritic cells to present antigenic peptide, present an HLA-E-restricted antigen, process and present an MHC class I-restricted antigen through the classical MHC class I pathway, and cross present cell-associated antigen via MHC class I. We found no defect in neonatal dendritic cells to perform any of these processing and presentation functions and conclude that the MHC class I antigen processing and presentation pathway is functional in neonatal dendritic cells and hence may not account for the diminished control of pathogens. C1 [Gold, Marielle C.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Dept Pulm & Crit Care Med, Portland, OR 97201 USA. [Gold, Marielle C.; Lewinsohn, David M.] Portland VA Med Ctr, Portland, OR USA. [Robinson, Tammie L.; Cook, Matthew S.; Byrd, Laura K.; Ehlinger, Heather D.; Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. RP Gold, MC (reprint author), Oregon Hlth & Sci Univ, Dept Pulm & Crit Care Med, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM goldm@ohsu.edu RI Lewinsohn, David/I-4936-2013; OI Lewinsohn, David/0000-0001-9906-9494; Gold, Marielle/0000-0003-2505-3291 FU NIH [5R01 AI054474] FX NIH 5R01 AI054474; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 10 Z9 10 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 26 PY 2007 VL 2 IS 9 AR e957 DI 10.1371/journal.pone.0000957 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10HT UT WOS:000207455800035 PM 17895997 ER PT J AU Parekkadan, B van Poll, D Suganuma, K Carter, EA Berthiaume, F Tilles, AW Yarmush, ML AF Parekkadan, Biju van Poll, Daan Suganuma, Kazuhiro Carter, Edward A. Berthiaume, Francois Tilles, Arno W. Yarmush, Martin L. TI Mesenchymal Stem Cell-Derived Molecules Reverse Fulminant Hepatic Failure SO PLOS ONE LA English DT Article AB Modulation of the immune system may be a viable alternative in the treatment of fulminant hepatic failure (FHF) and can potentially eliminate the need for donor hepatocytes for cellular therapies. Multipotent bone marrow-derived mesenchymal stem cells (MSCs) have been shown to inhibit the function of various immune cells by undefined paracrine mediators in vitro. Yet, the therapeutic potential of MSC-derived molecules has not been tested in immunological conditions in vivo. Herein, we report that the administration of MSC-derived molecules in two clinically relevant forms-intravenous bolus of conditioned medium (MSC-CM) or extracorporeal perfusion with a bioreactor containing MSCs (MSC-EB)-can provide a significant survival benefit in rats undergoing FHF. We observed a cell mass-dependent reduction in mortality that was abolished at high cell numbers indicating a therapeutic window. Histopathological analysis of liver tissue after MSC-CM treatment showed dramatic reduction of panlobular leukocytic infiltrates, hepatocellular death and bile duct duplication. Furthermore, we demonstrate using computed tomography of adoptively transferred leukocytes that MSC-CM functionally diverts immune cells from the injured organ indicating that altered leukocyte migration by MSC-CM therapy may account for the absence of immune cells in liver tissue. Preliminary analysis of the MSC secretome using a protein array screen revealed a large fraction of chemotactic cytokines, or chemokines. When MSC-CM was fractionated based on heparin binding affinity, a known ligand for all chemokines, only the heparin-bound eluent reversed FHF indicating that the active components of MSC-CM reside in this fraction. These data provide the first experimental evidence of the medicinal use of MSC-derived molecules in the treatment of an inflammatory condition and support the role of chemokines and altered leukocyte migration as a novel therapeutic modality for FHF. C1 [Parekkadan, Biju; van Poll, Daan; Suganuma, Kazuhiro; Carter, Edward A.; Berthiaume, Francois; Tilles, Arno W.; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02115 USA. [Parekkadan, Biju; van Poll, Daan; Suganuma, Kazuhiro; Carter, Edward A.; Berthiaume, Francois; Tilles, Arno W.; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA USA. [Parekkadan, Biju; Yarmush, Martin L.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA. [van Poll, Daan] Univ Utrecht, Univ Med Ctr, Dept Surg, Utrecht, Netherlands. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02115 USA. EM ireis@sbi.org FU National Science Foundation; Michael van Vlooten foundation; National Institutes of Health [K08 DK66040, K18 DK076819, R01 DK43371]; Shriners Hospitals for Children FX BP was supported by a National Science Foundation predoctoral fellowship. DVP was supported by a fellowship from the Michael van Vlooten foundation. This work was partially supported by grants from the National Institutes of Health (K08 DK66040, K18 DK076819 and R01 DK43371) and the Shriners Hospitals for Children. NR 15 TC 250 Z9 295 U1 4 U2 19 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 26 PY 2007 VL 2 IS 9 AR e941 DI 10.1371/journal.pone.0000941 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10HT UT WOS:000207455800020 PM 17895982 ER PT J AU Parikh, NI Hwang, SJ Larson, MG Cupples, LA Fox, CS Manders, ES Murabito, JM Massaro, JM Hoffmann, U O'Donnell, CJ AF Parikh, Nisha I. Hwang, Shih-Jen Larson, Martin G. Cupples, L. Adrienne Fox, Caroline S. Manders, Emily S. Murabito, Joanne M. Massaro, Joseph M. Hoffmann, Udo O'Donnell, Christopher J. TI Parental occurrence of premature cardiovascular disease predicts increased coronary artery and abdominal aortic calcification in the Framingham Offspring and Third Generation cohorts SO CIRCULATION LA English DT Article DE calcium; epidemiology; imaging; atherosclerosis; coronary disease; aorta ID ACUTE MYOCARDIAL-INFARCTION; CONVENTIONAL RISK-FACTORS; ISCHEMIC-HEART-DISEASE; FAMILY-HISTORY; SUBCLINICAL ATHEROSCLEROSIS; INDEPENDENT PREDICTOR; COMPUTED-TOMOGRAPHY; TASK-FORCE; CALCIUM; ADULTS AB Background-Parental premature cardiovascular disease (CVD) is a risk factor for coronary heart disease ( CHD). We related validated parental premature CVD with the subclinical measures of coronary artery (CAC) and abdominal aortic (AAC) calcification in the community. Methods and Results-We studied 2 generations of Framingham Heart Study subjects who underwent multidetector computed tomography measurements of CAC and AAC and who had 2 parents in the study. Subjects included 797 Framingham Offspring ( mean age, 63 years; 56% women) and 1238 Third Generation (Gen3) ( mean age, 46 years; 47% women) participants free of CVD. Generalized estimating equations adjusted for major CVD risk factors were used to relate validated parental premature CVD and CHD to CAC and AAC, defined by > 90th percentile age- and sex-specific cut points from a healthy subsample. Parental premature CVD was associated with CAC among Gen3 ( odds ratio=2.17 [1.41 to 3.33]; P < 0.001) and nonsignificantly among Offspring (odds ratio=1.42 [0.91 to 2.22]; P=0.12). Parental premature CHD was associated with CAC among Gen3 (odds ratio=2.22 [1.22 to 4.01]) but not Offspring. Parental premature CVD was not associated with AAC in either cohort. Parental premature CHD was associated with AAC among Gen3 (odds ratio=1.65 [0.99 to 2.75]; P=0.05) but not among Offspring. The magnitude of risk conferred was greater for paternal than maternal premature CVD. Conclusions-Parental premature CVD is associated with CAC, and premature CHD is associated with AAC, after adjustment for risk factors, particularly in younger middle-aged adults. Risk conferred by parental premature CVD on vascular calcification may be mediated through novel mechanisms not accounted for by classic CVD risk factors known to cause atherosclerosis. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), 73 Mt Wayte Ave 2, Framingham, MA 01702 USA. EM codonnell@nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Cupples, L. Adrienne/0000-0003-0273-7965; Murabito, Joanne/0000-0002-0192-7516 FU NHLBI NIH HHS [N01-HC-25195] NR 47 TC 69 Z9 69 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 25 PY 2007 VL 116 IS 13 BP 1473 EP 1481 DI 10.1161/CIRCULATIONAHA.107.705202 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 213VL UT WOS:000249695100007 PM 17785619 ER PT J AU Diamond, EL Miller, S Dickerson, BC Atri, A DePeau, K Fenstermacher, E Pihlajamaki, M Celone, K Salisbury, S Gregas, M Rentz, D Sperling, RA AF Diamond, E. L. Miller, S. Dickerson, B. C. Atri, A. DePeau, K. Fenstermacher, E. Pihlajamaeki, M. Celone, K. Salisbury, S. Gregas, M. Rentz, D. Sperling, R. A. TI Relationship of fMR1 activation to clinical trial memory measures in Alzheimer disease SO NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; HIPPOCAMPAL ACTIVATION; MRI; BRAIN; ATROPHY; AD; SEGMENTATION; PERFORMANCE AB Background: Functional MRI fMRI) has shown promise as a tool to characterize altered brain function in Alzheimer disease (AD) and for use in proof of concept clinical trials. FMRI studies of subjects with AD have demonstrated altered hippocampal and neocortical activation while encoding novel stimuli compared to older controls. However, the relationship between (fMRI) activation and performance on standardized clinical trial memory measures has not been fully investigated. Objective: To determine whether patterns of activation during an associative-memory fMRI paradigm correlate with performance on memory measures used in AD clinical trials. Methods: Twenty-nine subjects with AD underwent neuropsychological testing, including the AD Assessment Scale (ADAS-Cog), and an associative-encoding fMRI paradigm. Scores were entered as regressors in SPM2 analyses of the differential fMRI activation to novel-vs-repeated (NvR) stimuli. To account for cerebral atrophy, native-space structure-function analyses were performed with subjects' high-resolution structural images. Results: Performance on the ADAS-Cog verbal m emery component, and the ADAS-Cog total correlated with NvR activation in left superior temporal (p = 0.0003; r = -0.51) and left score, prefrontal (p = 0.00001; r = -0.63) cortices. In a subgroup with more extensive neuropsychological testing (n = 14), performance on the Free and Cued Selective Reminding Test was correlated activation remained correlated with with activation in these same regions. performance even when accounting for atrophy. Conclusions: The relationship between functional MRI (fMRI) activation and standardized memory measures supports the potential use of fMRI to investigate regional mechanisms of treatment response in clinical trials of novel therapies for Alzheimer disease. C1 Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Kuopio, Dept Neurosci & Neurol, FIN-70211 Kuopio, Finland. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Sperling, RA (reprint author), Brigham & Womens Hosp, Memory Disorders Unit, 221 Longwood Ave, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu OI Atri, Alireza/0000-0003-4405-6973 FU NIA NIH HHS [NIA-R01-AG027435, P50-AG00513421, NIA-PO1-AG04953]; PHS HHS [NIH-T32] NR 42 TC 27 Z9 28 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 25 PY 2007 VL 69 IS 13 BP 1331 EP 1341 DI 10.1212/01.wnl.0000277292.37292.69 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 213VI UT WOS:000249694800006 PM 17893294 ER PT J AU Chen, XH Kim, TD Carman, CV Mi, LZ Song, G Springer, TA AF Chen, Xuehui Kim, Thomas Doohun Carman, Christopher V. Mi, Li-Zhi Song, Gang Springer, Timothy A. TI Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE crystal structure; leukocytes; flow cytometry; mutagenesis ID INTERCELLULAR-ADHESION MOLECULE-1; CRYSTAL-STRUCTURE; BINDING; CADHERIN; INTEGRINS; SPECIFICITY; AFFINITY; REVEAL; LFA-1 AB The Ig superfamily (IgSF) intercellular adhesion molecule-1 (ICAM-1) equilibrates between monomeric and dimeric forms on the cell surface, and dimerization enhances cell adhesion. A crystal structure of ICAM-1 IgSF domains (D) 3-5 revealed a unique dimerization interface in which D4s of two protomers fuse through edge P-strands to form a single super beta-sandwich domain. Here, we describe a crystal structure at 2.7-angstrom resolution of monomeric ICAM-1 D3-D5, stabilized by the monomer-specific Fab CA7. CA7 binds to D5 in a region that is buried in the dimeric interface and is distal from the dimerization site in D4. In monomeric ICAM-1 D3-D5, a 16-residue loop in D4 that is disordered in the dimeric structure could clearly be traced as a BC loop, a short C strand, and a CE meander with a cis-Pro followed by a solvent-exposed, flexible four-residue region. Deletions of 6 or 10 residues showed that the C-strand is essential for monomer stability, whereas a distinct six-residue deletion showed little contribution of the CE meander. Mutation of two inward-pointing Leu residues in edge P-strand E to Lys increased monomer stability, confirming the hypothesis that inward-pointing charged side chains on edge beta-strands are an important design feature to prevent beta-supersheet formation. Overall, the studies reveal that monomer-dimer transition is associated with a surprisingly large, physiologically relevant, IgSF domain rearrangement. C1 Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. EM springeroffice@idi.harvard.edu RI Mi, Li-Zhi/B-1371-2016; Carman, Christopher/L-8108-2016 OI Mi, Li-Zhi/0000-0001-9907-5245; Carman, Christopher/0000-0001-7358-2548 FU NCI NIH HHS [CA31798, R01 CA031798, R37 CA031798] NR 29 TC 21 Z9 21 U1 3 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 25 PY 2007 VL 104 IS 39 BP 15358 EP 15363 DI 10.1073/pnas.0707406104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 215KJ UT WOS:000249806900035 PM 17881562 ER PT J AU Cotta-de-Almeida, V Westerberg, L Maillard, MH Onaldi, D Wachtel, H Meelu, P Chung, UI Xavier, R Alt, FW Snapper, SB AF Cotta-de-Almeida, Vinicius Westerberg, Lisa Maillard, Michel H. Onaldi, Dilek Wachtel, Heather Meelu, Parool Chung, Ung-il Xavier, Ramnik Alt, Frederick W. Snapper, Scott B. TI Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytoskeleton; thymus; migration; colitis; knockout mice ID IMMUNOLOGICAL SYNAPSE; LYMPHOCYTE DEVELOPMENT; ACTIN CYTOSKELETON; MEDULLA MIGRATION; ANTIGEN RECEPTOR; DEFICIENCY LEADS; FAMILY PROTEINS; EXCHANGE FACTOR; ACTIVATION; THYMOCYTES AB Although T cell dysfunction and lymphopenia are key features of immunodeficient patients with the Wiskott-Aldrich syndrome and Wiskott-Aldrich syndrome protein (WASP)-deficient mice, T cell development appears relatively normal. We hypothesized that N-WASP, a ubiquitously expressed homologue of WASP, may serve a redundant function with WASP. To examine the unique and redundant activities of WASP and N-WASP, we generated ES cells devoid of WASP and N-WASP [double knockout (DKO)] and used the RAG-2-deficient blastocyst complementation system to generate DKO lymphocytes. Moreover, we mated WASP KO mice with mice containing a conditionally targeted N-WASP allele and used the Cre-loxP system to generate mice lacking WASP and N-WASP in T cells [conditional DKO (cDKO)]. In both systems, N-WASP-deficient cells were indistinguishable from WT cells. In contrast, T cell development in DKO and cDKO mice was markedly altered, as shown by thymic hypocellularity and reduced numbers of periph- eral T cells. We found that the combined activity of WASP and N-WASP was important for CD4(-)CD8(-) double-negative (DN)-to-CD4(+)CD8(+) double-positive (DP) cell transition, and this may be partly explained by reduced cycling DN3 cells. In addition, decreased migratory responses of CD4(+)CD8(-) and CD4(-)CD8(+) single-positive (SP) cells and increased percentage of CD69(low)CD24(low) and CD62L(low) SP cells in cDKO cells imply retention of SP cells in the thymus. In summary, this study suggests that, although WASP serves a unique role for peripheral T cell function, T cell development depends on the combined activity of WASP and N-WASP. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Fiocruz MS, Inst Oswaldo Cruz, BR-21045900 Rio De Janeiro, Brazil. RP Alt, FW (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM alt@enders.tch.harvard.edu; ssnapper@hms.harvard.edu RI Cotta-de-Almeida, Vinicius/G-3939-2012; OI Westerberg, Lisa/0000-0003-2943-2192 FU NHLBI NIH HHS [P01 HL059561, HL59561]; NIAID NIH HHS [AI50950, R01 AI050950, R56 AI050950]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-12] NR 49 TC 50 Z9 50 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 25 PY 2007 VL 104 IS 39 BP 15424 EP 15429 DI 10.1073/pnas.0706881104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 215KJ UT WOS:000249806900046 PM 17878299 ER PT J AU Mueller, SN Matloubian, M Clemens, DM Sharpe, AH Freeman, GJ Gangappa, S Larsen, CP Ahmed, R AF Mueller, Scott N. Matloubian, Mehrdad Clemens, Daniel M. Sharpe, Arlene H. Freeman, Gordon J. Gangappa, Shivaprakash Larsen, Christian P. Ahmed, Rafi TI Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunopathology; stromal cells; viral infection ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; LYMPH-NODE; T-CELLS; DENDRITIC CELLS; MONOCLONAL-ANTIBODY; GLYCOPROTEIN; CHEMOKINES; CONDUIT; IMMUNODEFICIENCY; DESTRUCTION AB Many chronic viral infections are marked by pathogen persistence and a generalized immunosuppression. The exact mechanisms by which this occurs are still unknown. Using a mouse model of persistent lymphocytic choriomeningitis virus (LCMV) infection, we demonstrate viral targeting of fibroblastic reticular cells (FRC) in the lymphoid organs. The FRC stromal networks are critical for proper lymphoid architecture and function. High numbers of FRC were infected by LCMV clone 13, which causes a chronic infection, whereas few were infected by the acute strain, LCMV Armstrong. The function of the FRC conduit network was altered after clone 13 infection by the action of CD8(+) T cells. Importantly, expression of the inhibitory programmed death ligand 1, which was up-regulated on FRC after infection, reduced early CD8+ T cell-mediated immunopathology and prevented destruction of the FRC architecture in the spleen. Together, this reveals an important tropism during a persistent viral infection. These data also suggest that the inhibitory PD-1 pathway, which likely evolved to prevent excessive immunopathology, may contribute to viral persistence in FRC during chronic infection. C1 Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Univ Calif San Francisco, Dept Med, Div Rheumatol, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Div Infect Dis, Dept Med, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. RP Ahmed, R (reprint author), Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. EM ra@microbio.emory.edu RI Mueller, Scott/B-1918-2012; Larsen, Christian/B-6906-2012 OI Mueller, Scott/0000-0002-3838-3989; Larsen, Christian/0000-0001-6573-2649 FU NIAID NIH HHS [AI04464409, AI30048, AI56299, N01AI30048, P01 AI056299] NR 33 TC 113 Z9 113 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 25 PY 2007 VL 104 IS 39 BP 15430 EP 15435 DI 10.1073/pnas.0702579104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 215KJ UT WOS:000249806900047 PM 17878315 ER PT J AU Obst, R van Santen, HM Melamed, R Kamphorst, A Benoist, C Mathis, D AF Obst, Reinhard van Santen, Hisse-Martien Melamed, Rachel Kamphorst, Alice O. Benoist, Christophe Mathis, Diane TI Sustained antigen presentation can promote an immunogenic T cell response, like dendritic cell activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immune response; immune tolerance; regulated transgene; MHC class II ID MHC CLASS-II; IN-VIVO; ADAPTIVE IMMUNITY; TRANSGENIC MICE; RECEPTOR; STIMULATION; TOLERANCE; DETERMINES; NAIVE; LYMPHOCYTES AB Activation of dendritic cells (DCs) enhances their ability to prime naive T cells. How activation renders them immunogenic rather than tolerogenic is unclear. Here, we show, using temporally regulated expression of a transgene-encoded neoself antigen in DCs, that either prolonged antigen presentation or DC activation could elicit full expansion, effector cytokine production, and memory-cell differentiation. Microarray analysis of gene expression in T cells showed that all changes linked to DC activation through CD40 could be reproduced by persistent antigen delivery, suggesting that stabilization of antigen presentation is an important consequence of DC activation in vivo. In this system, DC activation by CD40 engagement indeed extended their ability to present antigen to CD4(+) T cells in vivo, although different results were obtained with antigen delivered to DCs by means of endocytosis from the cell surface. These results suggest that antigen persistence may be an important discriminator of immunogenic and tolerogenic antigen exposure. C1 Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Univ Munich, Inst Immunol, D-80336 Munich, Germany. Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. RP Benoist, C (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu RI van Santen, Hisse Martien/E-8103-2013; OI Melamed, Rachel/0000-0003-3089-9806 FU NIAID NIH HHS [R01 AI051530, R01 AI51530] NR 40 TC 43 Z9 44 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 25 PY 2007 VL 104 IS 39 BP 15460 EP 15465 DI 10.1073/pnas.0707331104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 215KJ UT WOS:000249806900052 PM 17881563 ER PT J AU Mutyala, S Choi, W Khan, AJ Yaparpalvi, R Stewart, AJ Devlin, PM AF Mutyala, Subhakar Choi, Walter Khan, Atif J. Yaparpalvi, Ravi Stewart, Alexandra J. Devlin, Phillip M. TI Inherent change in MammoSite applicator three-dimensional geometry over time SO RADIATION ONCOLOGY LA English DT Article ID BREAST BRACHYTHERAPY APPLICATOR; CANCER; OPTIMIZATION; THERAPY AB Accelerated partial breast irradiation is commonly done with the MammoSite applicator, which requires symmetry to treat the patient. This paper describes three cases that were asymmetric when initially placed and became symmetric over time, without manipulation. C1 [Mutyala, Subhakar; Choi, Walter; Yaparpalvi, Ravi] Montefiore Med Ctr, Dept Radiat Oncol, Bronx, NY 10467 USA. [Mutyala, Subhakar; Choi, Walter; Yaparpalvi, Ravi] Albert Einstein Coll Med, Dept Radiat Oncol, Bronx, NY 10467 USA. [Stewart, Alexandra J.] Royal Marsden Hosp, Dept Radiotherapy, Sutton, Surrey, England. [Khan, Atif J.; Devlin, Phillip M.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Khan, Atif J.; Devlin, Phillip M.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Mutyala, S (reprint author), Montefiore Med Ctr, Dept Radiat Oncol, 111 E 210th St, Bronx, NY 10467 USA. EM smutyala@montefiore.org; wachoi@montefiore.org; subrocker@yahoo.com; ryaparpa@montefiore.org; astewart@lroc.harvard.edu; pdevlin@lroc.harvard.edu OI Khan, Atif/0000-0001-8640-8530 NR 6 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND J9 RADIAT ONCOL JI Radiat. Oncol. PD SEP 24 PY 2007 VL 2 AR 37 DI 10.1186/1748-717X-2-37 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 364OB UT WOS:000260343900001 PM 17892557 ER PT J AU Gorry, PR McPhee, DA Verity, E Dyer, WB Wesselingh, SL Learmont, J Sullivan, JS Roche, M Zaunders, JJ Gabuzda, D Crowe, SM Mills, J Lewin, SR Brew, BJ Cunningham, AL Churchill, MJ AF Gorry, Paul R. McPhee, Dale A. Verity, Erin Dyer, Wayne B. Wesselingh, Steven L. Learmont, Jennifer Sullivan, John S. Roche, Michael Zaunders, John J. Gabuzda, Dana Crowe, Suzanne M. Mills, John Lewin, Sharon R. Brew, Bruce J. Cunningham, Anthony L. Churchill, Melissa J. TI Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo SO RETROVIROLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM SURVIVOR; BLOOD-BANK COHORT; RECOMBINANT GLYCOPROTEIN-120 VACCINE; CD4(+) T-CELLS; SLOW DISEASE PROGRESSION; TYPE-1 INFECTION; ANTIRETROVIRAL THERAPY; ANTIBODY-RESPONSES; NEUTRALIZING ANTIBODIES AB In efforts to develop an effective vaccine, sterilizing immunity to primate lentiviruses has only been achieved by the use of live attenuated viruses carrying major deletions in nef and other accessory genes. Although live attenuated HIV vaccines are unlikely to be developed due to a myriad of safety concerns, opportunities exist to better understand the correlates of immune protection against HIV infection by studying rare cohorts of long-term survivors infected with attenuated, nef-deleted HIV strains such as the Sydney blood bank cohort (SBBC). Here, we review studies of viral evolution, pathogenicity, and immune responses to HIV infection in SBBC members. The studies show that potent, broadly neutralizing anti-HIV antibodies and robust CD8+ T-cell responses to HIV infection were not necessary for long-term control of HIV infection in a subset of SBBC members, and were not sufficient to prevent HIV sequence evolution, augmentation of pathogenicity and eventual progression of HIV infection in another subset. However, a persistent T-helper proliferative response to HIV p24 antigen was associated with long-term control of infection. Together, these results underscore the importance of the host in the eventual outcome of infection. Thus, whilst generating an effective antibody and CD8+ T-cell response are an essential component of vaccines aimed at preventing primary HIV infection, T-helper responses may be important in the generation of an effective therapeutic vaccine aimed at blunting chronic HIV infection. C1 Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. Monash Univ, Dept Microbiol, Melbourne, Vic 3004, Australia. Monash Univ, Dept Epidemiol & Community Med, Melbourne, Vic 3004, Australia. St Vincents Inst Med Res, Natl Serol Reference Lab, Fitzroy, Vic 3065, Australia. Australian Red Cross Blood Serv, Sydney, NSW, Australia. Univ Sydney, Fac Med, Sydney, NSW 2006, Australia. St Vincents Hosp, Ctr Immunol, Sydney, NSW 2010, Australia. St Vincents Hosp, Dept Neurol, Sydney, NSW 2010, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Alfred Hosp, Infect Dis Unit, Melbourne, Vic, Australia. Westmead Millennim Inst, Westmead, NSW, Australia. RP Gorry, PR (reprint author), Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. EM gorry@burnet.edu.au; dale@nrl.gov.au; erin.verity@csl.com.au; WDyer@arcbs.redcross.org.au; stevew@burnet.edu.au; JLearmont@arcbs.redcross.org.au; JSullivan@arcbs.redcross.org.au; mroche@burnet.edu.au; j.zaunders@cfi.unsw.edu.au; dana_gabuzda@dfci.harvard.edu; crowe@burnet.edu.au; mills@portsea.net; s.lewin@alfred.org.au; b.brew@unsw.com.au; tony_cunningham@wmi.usyd.edu.au; churchil@burnet.edu.au RI Zaunders, John/J-6553-2012; Cunningham, Tony/B-7011-2013; Brew, Bruce/J-6513-2012; OI Zaunders, John/0000-0002-5912-5989; Roche, Michael/0000-0001-8819-0096; Lewin, Sharon Ruth/0000-0002-0330-8241; Cunningham, Anthony/0000-0002-6744-5667 FU NIAID NIH HHS [AI054207, R21 AI054207] NR 97 TC 42 Z9 42 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD SEP 23 PY 2007 VL 4 AR 66 DI 10.1186/1742-4690-4-66 PG 13 WC Virology SC Virology GA 234AW UT WOS:000251134000001 PM 17888184 ER PT J AU Moretti, FA Chauhan, AK Iaconcig, A Porro, F Baralle, FE Muro, AF AF Moretti, Federico A. Chauhan, Anil K. Iaconcig, Alessandra Porro, Fabiola Baralle, Francisco E. Muro, Andres F. TI A major fraction of fibronectin present in the extracellular matrix of tissues is plasma-derived SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INJURED ARTERIOLES; THROMBUS GROWTH; MESSENGER-RNA; SECRETION; EXPRESSION; SUBSTRATE; PROTEINS; BINDING; REGION; CELLS AB The origin of the fibronectin (FN) found in the extracellular matrix of tissues has not been defined experimentally. Previous studies suggest that there is contribution from both local tissue production and transfer from plasma, but the extent of this phenomenon has not been addressed. We have shown before that engineered mice constitutively expressing extra domain A-containing FN (EDA(+)FN) have a significant decrease of FN levels in plasma and most tissues. We showed that hepatocytes modified to produce EDA(+)FN have normal extracellular matrix-FN levels but secrete less soluble FN. When we performed a liver-specific EDiA-exon deletion in these animals, FN levels were restored both in plasma and tissues. Therefore, an important fraction of tissue FN, approximately an equal amount of that produced by the tissue itself, is actually plasma-derived, suggesting that plasma is an important source of tissue FN. The present results halve potential significance for understanding the contributions of plasma FN, and perhaps other plasma proteins, in the modulation of cellular activities and in the formation of the extracellular matrix of tissues. C1 Int Ctr Genet Engn & Biotechnol, I-34012 Trieste, Italy. RP Muro, AF (reprint author), Harvard Univ, Harvard Med Sch, CBR Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. EM muro@icgeb.org RI Muro, Andres/K-3156-2016 OI Muro, Andres/0000-0002-9628-0494 NR 33 TC 57 Z9 58 U1 0 U2 5 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 21 PY 2007 VL 282 IS 38 BP 28057 EP 28062 DI 10.1074/jbc.M611315200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 210KR UT WOS:000249455600055 PM 17644525 ER PT J AU Huttunen, HJ Guenette, SY Peach, C Greco, C Xia, WM Kim, DY Barren, C Tanzi, RE Kovacs, DM AF Huttunen, Henri J. Guenette, Suzanne Y. Peach, Camilla Greco, Christopher Xia, Weiming Kim, Doo Yeon Barren, Cory Tanzi, Rudolph E. Kovacs, Dora M. TI HtrA2 regulates beta-amyloid precursor protein (APP) metabolism through endoplasmic reticulum-associated degradation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE-PROTEASE; ALZHEIMERS-DISEASE; GAMMA-SECRETASE; LIPID RAFTS; CLEAVAGE; INHIBITOR; DOMAIN; PRESENILIN-1; OMI/HTRA2; STRESS AB Alzheimer disease-associated beta-amyloid peptide is generated from its precursor protein APP. By using the yeast two-hybrid assay, here we identified HtrA2/Omi, a stress-responsive chaperone-protease as a protein binding to the N-terminal cysteine-rich region of APP. HtrA2 coimmunoprecipitates exclusively with immature APP from cell lysates as well as mouse brain extracts and degrades APP in vitro. A subpopulation of HtrA2 localizes to the cytosolic side of the endoplasmic reticulum (ER) membrane where it contributes to ER-associated degradation of APP together with the proteasome, Inhibition of the proteasome results in accumulation of retrotranslocated forms of APP and increased association of APP with HtrA2 and Derlin-1 in microsomal membranes. In cells lacking HtrA2, APP holoprotein is stabilized and accumulates in the early secretory pathway correlating with elevated levels of APP C-terminal fragments and increased All secretion. Inhibition of ER-associated degradation (either HtrA2 or proteasome) promotes binding of APP to the COPII protein Sec23 suggesting enhanced trafficking of APP out of the ER. Based on these results we suggest a novel function for HtrA2 as a regulator of APP metabolism through ER-associated degradation. C1 Massachusetts Gen Hosp, Harvard Med Sch, Neurobiol Dis Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Harvard Med Sch, Massachussetts Gen Inst Nuerodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Harvard Med Sch, Ctr Neurol Dis, Boston, MA 02115 USA. RP Kovacs, DM (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Neurobiol Dis Lab, 114 16th St, Charlestown, MA 02129 USA. EM Dora_Kovacs@hms.harvard.edu RI xia, weiming/E-5465-2016; OI xia, weiming/0000-0002-7463-3295; Huttunen, Henri/0000-0002-9867-4438 NR 57 TC 55 Z9 58 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 21 PY 2007 VL 282 IS 38 BP 28285 EP 28295 DI 10.1074/jbc.M702951200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 210KR UT WOS:000249455600078 PM 17684015 ER PT J AU Ramasamy, S Duraisamy, S Barbashov, S Kawano, T Kharbanda, S Kufe, D AF Ramasamy, Selvi Duraisamy, Sekhar Barbashov, Sergei Kawano, Takeshi Kharbanda, Surender Kufe, Donald TI The MUC1 and galectin-3 oncoproteins function in a MicroRNA-dependent regulatory loop SO MOLECULAR CELL LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; GROWTH-FACTOR RECEPTOR; BETA-CATENIN; C-SRC; APOPTOTIC RESPONSE; INDUCED ACTIVATION; MESSENGER-RNA; FEEDBACK LOOP; DOMAIN; CELLS AB The MUC1 heterodimeric transmembrane glycoprotein is aberrantly overexpressed by diverse human carcinomas. Galectin-3 is a beta-galactoside binding protein that has also been associated with the development of human cancers. The present results demonstrate that MUC1 induces galectin-3 expression by a post-transcriptional mechanism. We show that the MUC1 C-terminal subunit is glycosylated on Asn-36 and that this modification is necessary for upregulation of galectin-3. N-glycosylated MUC1-C increases galectin-3 mRNA levels by suppressing expression of the microRNA miR-322 and thereby stabilizing galectin-3 transcripts. The results show that, in turn, galectin-3 binds to MUC1-C at the glycosylated Asn-36 site. The significance of the MUC1-C-galectin-3 interaction is supported by the demonstration that galectin-3 forms a bridge between MUC1 and the epidermal growth factor receptor (EGFR) and that galectin-3 is essential for EGF-mediated interactions between MUC1 and EGFR. These findings indicate that MUC1 and galectin-3 function as part of miR-322-dependent regulatory loop. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA97098, CA100707, P50 CA100707, R01 CA097098] NR 53 TC 101 Z9 104 U1 1 U2 10 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 21 PY 2007 VL 27 IS 6 BP 992 EP 1004 DI 10.1016/j.molcel.2007.07.031 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 215KZ UT WOS:000249808500015 PM 17889671 ER PT J AU Shen, KZ Kozell, LB Johnson, SW AF Shen, K.-Z. Kozell, L. B. Johnson, S. W. TI Multiple conductances are modulated by 5-HT receptor subtypes in rat subthalamic nucleus neurons SO NEUROSCIENCE LA English DT Article DE 5-HT; subthalamic nucleus; brain slice; patch clamp; burst firing ID EXTERNAL GLOBUS-PALLIDUS; LOCUS-CERULEUS NEURONS; DORSAL RAPHE NEURONS; MOTONEURONS IN-VITRO; BASAL GANGLIA; PARKINSONS-DISEASE; POTASSIUM CONDUCTANCE; K+ CURRENT; SEROTONIN; 5-HYDROXYTRYPTAMINE AB Firing patterns of subthalamic nucleus (STN) neurons influence normal and abnormal movements. The STN expresses multiple 5-HT receptor subtypes that may regulate neuronal excitability. We used whole-cell patch-clamp recordings to characterize 5-HT receptor-mediated effects on membrane currents in STN neurons in rat brain slices. In 80 STN neurons under voltage-clamp (-70 mV), 5-HT (30 mu M) evoked inward currents in 64%, outward currents in 17%, and biphasic currents in 19%. 5-HT-induced outward current was caused by an increased K+ conductance (1.4 +/- 0.2 nS) and was blocked by the 5-HT1A antagonist WAY 100135. The 5-HT-evoked inward current, which was blocked by antagonists at 5-HT2c and/or 5-HT4 receptors, had two types of current-voltage (I-V) relations. Currents associated with the type I I-V relation showed negative slope conductance at potentials < - 110 mV and were occluded by Ba2+. In contrast, the type 2 I-V relation appeared linear and had positive slope conductance (0.64 +/- 0.11 nS). Type 2 inward currents were Ba2+- insensitive, and the reversal potential of -19 mV suggests a mixed cation conductance. In STN neurons in which 5-HT evoked inward currents, 5-HT potentiated burst firing induced by N-methyl-D-aspartate (NMDA). But in neurons in which 5-HT evoked outward current, 5-HT slowed NMDA-dependent burst firing. We conclude that 5-HT receptor subtypes can differentially regulate firing pattern by modulating multiple conductances in STN neurons. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, R D 61, 3710 SW US Veterans Hosp Rd, Portland, OR 97207 USA. EM johnsost@ohsu.edu OI Kozell, Laura/0000-0003-3059-2046 FU NINDS NIH HHS [NS38175, R01 NS038175, R01 NS038715, R01 NS038715-08] NR 50 TC 17 Z9 19 U1 0 U2 2 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 21 PY 2007 VL 148 IS 4 BP 996 EP 1003 DI 10.1016/j.neuroscience.2007.07.012 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 216WF UT WOS:000249909000015 PM 17706881 ER PT J AU Junt, T Schulze, H Chen, Z Massberg, S Goerge, T Krueger, A Wagner, DD Graf, T Italiano, JE Shivdasani, RA von Andrian, UH AF Junt, Tobias Schulze, Harald Chen, Zhao Massberg, Steffen Goerge, Tobias Krueger, Andreas Wagner, Denisa D. Graf, Thomas Italiano, Joseph E., Jr. Shivdasani, Ramesh A. von Andrian, Ulrich H. TI Dynamic visualization of thrombopoiesis within bone marrow SO SCIENCE LA English DT Article ID TRANSCRIPTION FACTOR NF-E2; IN-VIVO; PLATELET-RELEASE; PROPLATELET FORMATION; HUMAN MEGAKARYOCYTES; MICE; THROMBOCYTOPOIESIS; HEMATOPOIESIS; BIOGENESIS; CELLS AB Platelets are generated from megakaryocytes (MKs) in mammalian bone marrow (BM) by mechanisms that remain poorly understood. Here we describe the use of multiphoton intravital microscopy in intact BM to visualize platelet generation in mice. MKs were observed as sessile cells that extended dynamic proplatelet-like protrusions into microvessels. These intravascular extensions appeared to be sheared from their transendothelial stems by flowing blood, resulting in the appearance of proplatelets in peripheral blood. In vitro, proplatelet production from differentiating MKs was enhanced by fluid shear. These results confirm the concept of proplatelet formation in vivo and are consistent with the possibility that blood flow-induced hydrodynamic shear stress is a biophysical determinant of thrombopoiesis. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Ctr Regulacio Genom, Barcelona 08003, Spain. RP von Andrian, UH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu; uva@hms.harvard.edu RI Krueger, Andreas/B-9427-2009; von Andrian, Ulrich/A-5775-2008; Graf, Thomas/B-4252-2015 OI Krueger, Andreas/0000-0001-7873-7334; Graf, Thomas/0000-0003-2774-4117 FU NHLBI NIH HHS [HL068130, HL56949, HL63143] NR 27 TC 279 Z9 288 U1 7 U2 28 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 21 PY 2007 VL 317 IS 5845 BP 1767 EP 1770 DI 10.1126/science.1146304 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 212HD UT WOS:000249585900053 PM 17885137 ER PT J AU Talcott, JA AF Talcott, James A. TI Prostate cancer quality of life: Beyond initial treatment-and the patient SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CHEMOTHERAPY; RADIATION; SURVIVORS; OUTCOMES; ANTIGEN; MEN; END C1 Massachusetts Gen Hosp, Massachusetts Gen Hosp Canc Ctr, Ctr Outcomes Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Hosp Canc Ctr, Ctr Outcomes Res, Boston, MA 02114 USA. NR 20 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2007 VL 25 IS 27 BP 4155 EP 4156 DI 10.1200/JCO.2007.12.1996 PG 2 WC Oncology SC Oncology GA 233EM UT WOS:000251073200001 PM 17635949 ER PT J AU Mayer, RJ AF Mayer, Robert J. TI Should capecitabine replace infusional fluorouracil and leucovorin when combined with oxaliplatin in metastatic colorectal cancer? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID III COLON-CANCER; ORAL CAPECITABINE; PHASE-III; ADJUVANT TREATMENT; PLUS LEUCOVORIN; THERAPY; 5-FLUOROURACIL/LEUCOVORIN; FLUOROPYRIMIDINES; BEVACIZUMAB; IRINOTECAN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 25 TC 23 Z9 24 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2007 VL 25 IS 27 BP 4165 EP 4167 DI 10.1200/JCO.2007.11.6582 PG 3 WC Oncology SC Oncology GA 233EM UT WOS:000251073200005 PM 17709796 ER PT J AU Heymach, JV Johnson, BE Prager, D Csada, E Roubec, J Pesek, M Spasova, I Belani, CP Bodrogi, I Gadgeel, S Kennedy, SJ Hou, J Herbst, RS AF Heymach, John V. Johnson, Bruce E. Prager, Diane Csada, Edit Roubec, Jaromir Pesek, Milos Spasova, Irena Belani, Chandra P. Bodrogi, Istvan Gadgeel, Shirish Kennedy, Sarah J. Hou, Jeannie Herbst, Roy S. TI Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID RECEPTOR TYROSINE KINASE; MALIGNANT-TUMORS; SUPPORTIVE CARE; SOLID TUMORS; TRIAL; CHEMOTHERAPY; GEFITINIB; ERLOTINIB; BEVACIZUMAB; CARBOPLATIN AB Purpose Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor kinase activity. The activity of vandetanib plus docetaxel was assessed in patients with previously treated non-small-cell lung cancer (NSCLC). Patients and Methods This two-part study comprised an open-label run-in phase and a double-blind randomized phase. Eligible patients had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of first-line platinum-based chemotherapy. The primary objective of the randomized phase was to prolong progression-free survival (PFS) in patients receiving vandetanib (100 or 300 mg/d) plus docetaxel (75 mg/m(2) intravenous infusion every 21 days) versus placebo plus docetaxel. The study was designed to have more than 75% power to detect 50% prolongation at a one-sided significance level of P < .20. Secondary objectives included objective response rate, overall survival, safety and tolerability. Results In the randomized phase (n = 127), median PFS was 18.7 weeks for vandetanib 100 mg plus docetaxel (n = 42; hazard ratio v docetaxel = 0.64; one-sided P = .037); 17.0 weeks for vandetanib 300 mg plus docetaxel (n = 44; hazard ratio v docetaxel = 0.83; one- sided P = .231); and 12 weeks for docetaxel (n = 41). There was no statistically significant difference in overall survival among the three treatment arms. Common adverse events included diarrhea, rash, and asymptomatic prolongation of corrected QT (QT(C)) interval. Conclusion The primary objective was achieved, with vandetanib 100 mg plus docetaxel demonstrating a significant prolongation of PFS compared with docetaxel in relation to the prespecified significance level. On the basis of these encouraging data, phase III evaluation of vandetanib 100 mg plus docetaxel in second-line NSCLC has been initiated. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Szeged, Szeged, Hungary. Natl Inst Oncol, Budapest, Hungary. Univ Ostrava, Univ Hosp Ostrava, CZ-70852 Ostrava, Czech Republic. Charles Univ Prague, Med Fac Pilsen, Univ Hosp, Prague, Czech Republic. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. AstraZeneca, Macclesfield, Cheshire, England. Astra Zeneca, Wilmington, DE USA. RP Herbst, RS (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd,Unit 432, Houston, TX 77030 USA. EM rherbst@mdanderson.org OI Belani, Chandra/0000-0001-5049-5329 NR 29 TC 214 Z9 219 U1 0 U2 13 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2007 VL 25 IS 27 BP 4270 EP 4277 DI 10.1200/JCO.2006.10.5122 PG 8 WC Oncology SC Oncology GA 233EM UT WOS:000251073200020 PM 17878479 ER PT J AU Staley, KJ AF Staley, Kevin J. TI Neurons skip a beat during fast ripples SO NEURON LA English DT Editorial Material ID EPILEPTIC BRAIN; HIPPOCAMPAL; OSCILLATIONS; INTERNEURONS AB Fast ripples are EEG transients emanating from epileptic foci, but fast-ripple frequencies far exceed maximal neuronal firing rates. In this issue of Neuron, Menendez de la Prida and coworkers propose that out-of-phase firing of a subpopulation of neurons during physiological ripple activity effectively doubles the ripple frequency to produce fast ripples. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurol, Boston, MA 02114 USA. RP Staley, KJ (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM kstaley@partners.org NR 12 TC 16 Z9 16 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 20 PY 2007 VL 55 IS 6 BP 828 EP 830 DI 10.1016/j.neuron.2007.09.005 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 219IQ UT WOS:000250078500002 PM 17880888 ER PT J AU Plenge, RM Seielstad, M Padyukov, L Lee, AT Remmers, EF Ding, B Liew, A Khalili, H Chandrasekaran, A Davies, LRL Li, WT Tan, AKS Bonnard, C Ong, RTH Thalamuthu, A Pettersson, S Liu, CY Tian, C Chen, WV Carulli, JP Beckman, EM Altshuler, D Alfredsson, L Criswell, LA Amos, CI Seldin, MF Kastner, DL Klareskog, L Gregersen, PK AF Plenge, Robert M. Seielstad, Mark Padyukov, Leonid Lee, Annette T. Remmers, Elaine F. Ding, Bo Liew, Anthony Khalili, Houman Chandrasekaran, Alamelu Davies, Leela R. L. Li, Wentian Tan, Adrian K. S. Bonnard, Carine Ong, Rick T. H. Thalamuthu, Anbupalam Pettersson, Sven Liu, Chunyu Tian, Chao Chen, Wei V. Carulli, John P. Beckman, Evan M. Altshuler, David Alfredsson, Lars Criswell, Lindsey A. Amos, Christopher I. Seldin, Michael F. Kastner, Daniel L. Klareskog, Lars Gregersen, Peter K. TI TRAF1-C5 as a risk locus for rheumatoid arthritis - A genomewide study SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; WIDE ASSOCIATION; SHARED EPITOPE; SUSCEPTIBILITY GENES; MONOCLONAL-ANTIBODY; LINKAGE; FAMILIES; PTPN22; POWER; IDENTIFICATION AB Background Rheumatoid arthritis has a complex mode of inheritance. Although HLA-DRB1 and PTPN22 are well-established susceptibility loci, other genes that confer a modest level of risk have been identified recently. We carried out a genomewide association analysis to identify additional genetic loci associated with an increased risk of rheumatoid arthritis. Methods We genotyped 317,503 single-nucleotide polymorphisms (SNPs) in a combined case-control study of 1522 case subjects with rheumatoid arthritis and 1850 matched control subjects. The patients were seropositive for autoantibodies against cyclic citrullinated peptide (CCP). We obtained samples from two data sets, the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Results from NARAC and EIRA for 297,086 SNPs that passed quality-control filters were combined with the use of Cochran-Mantel-Haenszel stratified analysis. SNPs showing a significant association with disease (P<1 x 10(-8)) were genotyped in an independent set of case subjects with anti-CCP-positive rheumatoid arthritis (485 from NARAC and 512 from EIRA) and in control subjects (1282 from NARAC and 495 from EIRA). Results We observed associations between disease and variants in the major-histocompatibility-complex locus, in PTPN22, and in a SNP (rs3761847) on chromosome 9 for all samples tested, the latter with an odds ratio of 1.32 (95% confidence interval, 1.23 to 1.42; P=4 x 10(-14)). The SNP is in linkage disequilibrium with two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis factor receptor-associated factor 1) and C5 (encoding complement component 5). Conclusions A common genetic variant at the TRAF1-C5 locus on chromosome 9 is associated with an increased risk of anti-CCP-positive rheumatoid arthritis. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Davis, Rowe Program, Davis, CA 95616 USA. Biogen Idec, Cambridge, MA USA. NIAMSD, Bethesda, MD 20892 USA. N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. Karolinska Inst, Stockholm, Sweden. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Genome Inst Singapore, Singapore, Singapore. Brigham & Womens Hosp, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. RP Plenge, RM (reprint author), N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, 350 Community Dr, Manhasset, NY 11030 USA. RI Padyukov, Leonid/A-4890-2009; Altshuler, David/A-4476-2009; Pettersson, Sven/F-9511-2015; OI Padyukov, Leonid/0000-0003-2950-5670; Altshuler, David/0000-0002-7250-4107; Seielstad, Mark/0000-0001-5783-1401; Alfredsson, Lars/0000-0003-1688-6697; Li, Wentian/0000-0003-1155-110X; Klareskog, Lars/0000-0001-9601-6186 FU Intramural NIH HHS; NCRR NIH HHS [5-M01-RR-00079, M01 RR000079, M01 RR018535, M01-RR018535]; NIAID NIH HHS [K08 AI055314, K08 AI055314-01A1, K08 AI055314-02, K08 AI055314-03, K08 AI055314-04, K08 AI055314-05, K08-AI55314-3, R01 AI065841, R01-AI065841]; NIAMS NIH HHS [K24 AR002175, K24-AR02175, N01-AR22263, N01AR22263, R01 AR044422, R01 AR050267, R01-AR050267, R01-AR44422] NR 50 TC 504 Z9 522 U1 5 U2 20 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 20 PY 2007 VL 357 IS 12 BP 1199 EP 1209 DI 10.1056/NEJMoa073491 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 211RM UT WOS:000249541000005 PM 17804836 ER PT J AU Ryan, ET Aquino, SL Kradin, RL McDonough, AL AF Ryan, Edward T. Aquino, Suzanne L. Kradin, Richard L. McDonough, Allison L. TI A 51-year-old man with gastric cancer and lung nodules - Schistosoma mansoni infection with pulmonary involvement. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HELICOBACTER-PYLORI INFECTION; JAPANESE BRAZILIANS; STOMACH-CANCER; RISK-FACTORS; SAO-PAULO; CARCINOMA; PARAGONIMIASIS; DIAGNOSIS; STRAINS; ESOPHAGEAL C1 Harvard Univ, Sch Med, Div Infect Dis, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Ryan, ET (reprint author), Harvard Univ, Sch Med, Div Infect Dis, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 21 TC 0 Z9 1 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 20 PY 2007 VL 357 IS 12 BP 1239 EP 1246 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 211RM UT WOS:000249541000011 PM 17881756 ER PT J AU Brown, EN Kass, RE AF Brown, Emery N. Kass, Robert E. TI Special issue on 'statistical analysis of neuronal data' SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA. RP Brown, EN (reprint author), MIT, Dept Brain & Cognit Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 20 PY 2007 VL 26 IS 21 BP 3827 EP 3829 DI 10.1002/sim.2982 PG 3 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 212CY UT WOS:000249572400001 ER PT J AU Feinberg, MW Wara, AK Cao, Z Lebedeva, MA Rosenbauer, F Iwasaki, H Hirai, H Katz, JP Haspel, RL Gray, S Akashi, K Segre, J Kaestner, KH Tenen, DG Jain, MK AF Feinberg, Mark W. Wara, Akm Khyrul Cao, Zhuoxiao Lebedeva, Maria A. Rosenbauer, Frank Iwasaki, Hiromi Hirai, Hideyo Katz, Jonathan P. Haspel, Richard L. Gray, Susan Akashi, Koichi Segre, Julie Kaestner, Klaus H. Tenen, Daniel G. Jain, Mukesh K. TI The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation SO EMBO JOURNAL LA English DT Article DE hematopoietic progenitors; Kruppels; leukemia; monocyte differentiation; PU.1 ID COLONY-STIMULATING FACTOR; TRANSCRIPTION FACTOR PU.1; HEMATOPOIETIC STEM-CELLS; BINDING PROTEIN ALPHA; T-CELL; LINEAGE COMMITMENT; ERYTHROID-CELLS; C/EBP-ALPHA; FACTOR EKLF; GRANULOCYTE AB Monocyte differentiation involves the participation of line-age-restricted transcription factors, although the mechanisms by which this process occurs are incompletely defined. Within the hematopoietic system, members of the Kruppel-like family of factors ( KLFs) play essential roles in erythrocyte and T lymphocyte development. Here we show that KLF4/ GKLF is expressed in a monocyte- restricted and stage- specific pattern during myelopoiesis and functions to promote monocyte differentiation. Overexpression of KLF4 in HL- 60 cells confers the characteristics of mature monocytes. Conversely, KLF4 knockdown blocked phorbol ester- induced monocyte differentiation. Forced expression of KLF4 in primary common myeloid progenitors ( CMPs) or hematopoietic stem cells ( HSCs) induced exclusive monocyte differentiation in clonogenic assays, whereas KLF4 deficiency inhibited monocyte but increased granulocyte differentiation. Mechanistic studies demonstrate that KLF4 is a target gene of PU.1. Consistently, KLF4 can rescue PU.1-/- fetal liver cells along the monocytic lineage and can activate the monocytic- specific CD14 promoter. Thus, KLF4 is a critical regulator in the transcriptional network controlling monocyte differentiation. C1 Brigham & Womens Hosp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Inst Med, Boston, MA USA. Dana Farber Canc Inst, Dept Canc & Immunol & AIDS, Boston, MA USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Case Cardiovasc Res Inst, Cleveland, OH 44106 USA. RP Jain, MK (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM Mukesh.Jain2@case.edu OI Rosenbauer, Frank/0000-0001-7977-9421; Tenen, Daniel/0000-0002-6423-3888 FU NHLBI NIH HHS [K08 HL067755, HL 080174, HL-72952, HL-75427, HL-76754, HL03747, HL67755, HL69477, R01 HL069477, R01 HL072952, R01 HL075427, R01 HL076754, R01 HL080174] NR 44 TC 128 Z9 136 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 19 PY 2007 VL 26 IS 18 BP 4138 EP 4148 DI 10.1038/sj.emboj.7601824 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 213UF UT WOS:000249691900008 PM 17762869 ER PT J AU Seeram, NP Aronson, WJ Zhang, Y Henning, SM Moro, A Lee, RP Sartippour, N Harris, DM Rettig, M Suchard, MA Pantuck, AJ Belldegrun, A Heber, D AF Seeram, Navindra P. Aronson, William J. Zhang, Yanjun Henning, Susanne M. Moro, Aune Lee, Ru-Po Sartippour, Niaryam Harris, Diane M. Rettig, Matthew Suchard, Marc A. Pantuck, Allan J. Belldegrun, Arie Heber, David TI Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE pomegranate; ellagitannins; urolithins; metabolite; tissue disposition; prostate cancer ID ELLAGIC ACID; HUMAN PLASMA; JUICE; BIOAVAILABILITY; ANTIOXIDANT; POLYPHENOLS; PUNICALAGIN; EXTRACT; CELLS; RAT AB Our group has shown in a phase 11 clinical trial that pomegranate juice (PJ) increases prostate specific antigen (PSA) doubling time in prostate cancer (CaP) patients with a rising PSA. Ellagitannins (ETs) are the most abundant polyphenols present in PJ and contribute greatly towards its reported biological properties. On consumption, ETs hydrolyze to release ellagic acid (EA), which is then converted by gut microflora. to 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one (urolithin A, UA) derivatives. Despite the accumulating knowledge of ET metabolism in animals and humans, there is no available data on the pharmacokinetics and tissue disposition of urolithins. Using a standardized ET-enriched pomegranate extract (PE), we sought to further define the metabolism and tissue distribution of ET metabolites. PE and UA (synthesized in our laboratory) were administered to C57BL/6 wild-type male mice, and metabolite levels in plasma and tissues were determined over 24 h. ET metabolites were concentrated at higher levels in mouse prostate, colon, and intestinal tissues as compared to other tissues after administration of PE or UA. We also evaluated the effects of PE on CaP growth in severe combined immunodeficient (SCID) mice injected subcutaneously with human CaP cells (LAPC-4). PE significantly inhibited LAPC-4 xenograft growth in SCID mice as compared to vehicle control. Finally, EA and several synthesized urolithins were shown to inhibit the growth of human CaP cells in vitro. The chemopreventive potential of pomegranate ETs and localization of their bioactive metabolites in mouse prostate tissue suggest that pomegranate may play a role in CaP treatment and chemoprevention. This warrants future human tissue bioavailability studies and further clinical studies in men with CaP. C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Greater Los Angeles VA Med Ctr, Los Angeles, CA 90095 USA. RP Seeram, NP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, Los Angeles, CA 90095 USA. EM nseeram@mednet.ucla.edu FU NCI NIH HHS [CA 42710, P50 CA 92131]; NIDDK NIH HHS [T32 DK07688] NR 21 TC 122 Z9 125 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD SEP 19 PY 2007 VL 55 IS 19 BP 7732 EP 7737 DI 10.1021/jf071303g PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 210KM UT WOS:000249455100017 PM 17722872 ER PT J AU Schmitz, K Haggarty, SJ McPherson, OM Clardy, J Koehler, AN AF Schmitz, Katja Haggarty, Stephen J. McPherson, Olivia M. Clardy, Jon Koehler, Angela N. TI Detecting binding interactions using microarrays of natural product extracts SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RAPAMYCIN AY-22,989; DRUG DISCOVERY; MOLECULES; CHEMISTRY; LIBRARIES AB Small-molecule microarrays have been used to discover biologically active small molecules in collections of synthetic compounds. Here we utilize a versatile isocyanate chemistry to immobilize extracts from microorganisms in a microarray format. Specific bioactive small molecules are detected in crude extracts of Streptomyces hygroscopicus, and the amount of specific to nonspecific binding of a protein to an immobilized compound on a microarray can be estimated. These natural product-extract microarrays (NPEMs) provide new tools for characterizing the metabolic products of organisms and for discovering biologically active small molecules from nature. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Koehler, AN (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. EM koehler@fas.harvard.edu RI Schmitz, Katja/B-9342-2008; OI Schmitz, Katja/0000-0001-9023-318X; Haggarty, Stephen J./0000-0002-7872-168X FU NCI NIH HHS [CA59021, N01-CO-12400]; NIMH NIH HHS [R21MH076146] NR 14 TC 16 Z9 16 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 19 PY 2007 VL 129 IS 37 BP 11346 EP + DI 10.1021/ja073965a PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 210OG UT WOS:000249464900025 PM 17718493 ER PT J AU Welch, HG Fisher, ES Gottlieb, DJ Barry, MJ AF Welch, H. Gilbert Fisher, Elliott S. Gottlieb, Daniel J. Barry, Michael J. TI Detection of prostate cancer via biopsy in the medicare-SEER population during the PSA era SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ANTIGEN; SEXTANT; CARCINOMA; WHITE; MEN; AGE AB Background Despite the considerable attention given to the prostate-specific antigen (PSA) as a screening test for prostate cancer, it is needle biopsy-and not the PSA test result-that actually establishes the diagnosis of prostate cancer. We sought national estimates on the proportion of men found to have prostate cancer after a needle biopsy of the prostate and the risk of subsequent biopsies among those not found to have prostate cancer. Methods We linked Medicare claims data to Surveillance, Epidemiology, and End Results (SEER) data to analyze outcomes after 10429 needle biopsies performed in 1993 through 2001 in 8273 men aged 65 years and older enrolled in Medicare Part B who resided in a SEER area. We determined the proportion of needle biopsies that were followed by a diagnosis of prostate cancer, the cumulative risk of prostate cancer following multiple biopsies, and the risk of subsequent biopsy among men not found to have prostate cancer in the previous biopsy. All statistical tests were two-sided. Results The overall proportion of needle biopsies found to contain prostate cancer was 32% (95% confidence interval [Cl] = 31% to 33%). The yield increased with age (26% for men aged 65-69 years, 31% for men aged 70-74 years, 35% for men aged 75-79 years, and 41% for men aged 80 years and older; P-trend <.001). The cumulative risk of prostate cancer diagnosis increased with repeated biopsy, with 50% of men receiving a prostate cancer diagnosis after two biopsies, 62% after three biopsies, and 68% after four biopsies. Among men whose first recorded biopsy did not detect prostate cancer, the risk of having a subsequent biopsy was 11.6% (95% Cl = 11 % to 12%) at 1 year and 38% (95% Cl = 36% to 40%) at 5 years. Conclusions About one-third of prostate biopsies identified prostate cancer in this population. Men not found to have prostate cancer on a first biopsy frequently undergo repeat biopsies, which raise the cumulative risk of prostate cancer diagnosis. C1 Dept Vet Affairs Med Ctr, White River Jct, VT USA. Inst Hlth Policy & Clin Pract, Hanover, NH USA. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. RP Welch, HG (reprint author), Dept Vet Affairs Med Ctr, VA Outcomes Grp, White River Jct, VT 05009 USA. EM h.gilbert.welch@dartmouth.edu FU NCI NIH HHS [CA107124] NR 20 TC 73 Z9 75 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 19 PY 2007 VL 99 IS 18 BP 1395 EP 1400 DI 10.1093/jnci/djm119 PG 6 WC Oncology SC Oncology GA 214EJ UT WOS:000249718500011 PM 17848671 ER PT J AU Plomondon, ME Ho, PM Wang, L Greiner, GT Shore, JH Sakai, JT Fihn, SD Rumsfeld, JS AF Plomondon, Mary E. Ho, P. Michael Wang, Li Greiner, Gwendolyn T. Shore, James H. Sakai, Joseph T. Fihn, Stephan D. Rumsfeld, John S. TI Severe mental illness and mortality of hospitalized ACS patients in the VHA SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; HEALTH-CARE-SYSTEM; GENDER DISPARITIES; HEART-DISEASE; MANAGEMENT; DISORDERS; REVASCULARIZATION; OUTCOMES; QUALITY AB Background: Severe mental illness (SMI) has been associated with more medical co-morbidity and less cardiovascular procedure use for older patients with myocardial infarction. However, it is unknown whether SMI is associated with increased long term mortality risk among patients presenting with acute coronary syndromes (ACS). We tested the hypothesis that SMI is associated with higher one-year mortality following ACS hospitalization. Methods: All ACS patients (n = 14,194) presenting to Veterans Health Administration (VHA) hospitals between October 2003 and September 2005 were included. Survival analysis evaluated the association between SMI and one-year all-cause mortality, adjusting for demographics, co-morbidities, in-hospital treatment, and discharge medications. Results: Overall, 18.4 % of ACS patients had SMI. Patients with SMI were more likely female, younger, Caucasian race, have a history of alcohol abuse, liver disease, dementia, hypertension and more likely to be a current smoker; however, prior cardiac history was similar between the 2 groups. There were no significant differences in cardiac procedure use, including coronary angiogram (38.7% vs. 40.3%, p = 0.14) or coronary revascularization (31.0% vs. 32.3%, p = 0.19), and discharge medications between those with and without SMI. One-year mortality was lower for patients with SMI (15.8% vs. 19.1%, p < 0.001). However, in multivariable analysis, there were no significant differences in mortality (HR 0.91; 95% Cl 0.81-1.02) between patients with and without SMI. Conclusion: Among ACS patients in the VHA, SMI is prevalent, affecting almost 1 in 5 patients. However, patients with SMI were as likely to undergo coronary revascularization and be prescribed evidence-based medications at hospital discharge, and were not at elevated risk of adverse 1-year outcomes compared to patients without SMI. C1 Denver VA Med Ctr, Cardiol Sect, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO USA. Puget Sound Hlth Care Ctr, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO USA. RP Plomondon, ME (reprint author), Denver VA Med Ctr, Cardiol Sect, Denver, CO USA. EM meg.plomondon@va.gov; michael.ho@va.gov; li.wang2@va.gov; gwendolyn.greiner@va.gov; jay.shore@uchsc.edu; joseph.sakai@uchsc.edu; stephan.fihn@va.gov; John.Rumsfeld@va.gov NR 20 TC 17 Z9 18 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD SEP 18 PY 2007 VL 7 AR 146 DI 10.1186/1472-6963-7-146 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 234NC UT WOS:000251169800001 PM 17877804 ER PT J AU Katiyar, SK AF Katiyar, Santosh K. TI UV-induced immune suppression and photocarcino genesis: Chemoprevention by dietary botanical agents SO CANCER LETTERS LA English DT Review DE chemoprevention; DNA repair; immunosuppression; interleukins; photocarcinogenesis; ultraviolet radiation ID RADIATION-INDUCED IMMUNOSUPPRESSION; HEART-TRANSPLANT RECIPIENTS; DELAYED-TYPE HYPERSENSITIVITY; GREEN TEA POLYPHENOLS; SKIN-CANCER; ULTRAVIOLET-RADIATION; CONTACT HYPERSENSITIVITY; DNA-REPAIR; IN-VIVO; PREVENTS PHOTOCARCINOGENESIS AB Studies of immune-suppressed transplant recipients and patients with biopsy-proven skin cancer have confirmed that ultraviolet (UV) radiation-induced immune suppression is a risk factor for the development of skin cancer in humans. UV radiation suppresses the immune system in several ways. The UVB spectrum inhibits antigen presentation, induces the release of immunosuppressive cytokines, and elicits DNA damage that is a molecular trigger of UV-mediated immunosuppression. It is therefore important to elucidate the mechanisms underlying UV-induced immunosuppression as a basis for developing strategies to protect individuals from this effect and subsequent development of skin cancer. Dietary botanicals are of particular interest as they have been shown to inhibit UV-induced immune suppression and photocarcinogenesis. In this review, we summarize the most recent investigations and mechanistic studies regarding the photoprotective efficacy of selected dietary agents, including, green tea polyphenols, grape seed proanthocyanidins and silymarin. We present evidence that these chemopreventive agents prevent UVB-induced immunosuppression and photocarcinogenesis through: (i) the induction of immunoregulatory cytokine interleukin (IL)-12; (ii) IL-12-dependent DNA repair; and (iii) stimulation of cytotoxic T cells in the tumor microenvironment. The new information regarding the mechanisms of action of these agents supports their potential use as adjuncts in the prevention of photocarcinogenesis. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Univ Alabama, Dept Environm Hlth Sci, Birmingham, AL 35294 USA. Univ Alabama, Clin Nutr Res Ctr, Birmingham, AL 35294 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCCIH NIH HHS [AT002536, R01 AT002536, R01 AT002536-02]; NCI NIH HHS [R21 CA104428-01A2, CA089738, CA104428, CA105368, R03 CA089738, R03 CA105368, R03 CA105368-02, R21 CA104428, R21 CA104428-02]; NIEHS NIH HHS [ES11421] NR 60 TC 66 Z9 70 U1 2 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD SEP 18 PY 2007 VL 255 IS 1 BP 1 EP 11 DI 10.1016/j.canlet.2007.02.010 PG 11 WC Oncology SC Oncology GA 210XK UT WOS:000249488700001 PM 17382466 ER PT J AU Cole, AJ AF Cole, Andrew J. TI Hippocampal sclerosis - An inflammatory hypothesis SO NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, MGH Epilepsy Serv, Fruit St, Boston, MA 02114 USA. EM cole.andrew@mgh.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 18 PY 2007 VL 69 IS 12 BP 1204 EP 1205 DI 10.1212/01.wnl.0000279585.36404.d0 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 211PR UT WOS:000249536200002 PM 17875908 ER PT J AU Moller, B Light, GA Fitzgerald, PB Snyder, JS Chen, R Daskalakis, ZJ AF Moeller, Bertram Light, Gregory A. Fitzgerald, Paul B. Snyder, Joel S. Chen, Robert Daskalakis, Zafiris J. TI Relationship between P50 suppression and the cortical silent period SO NEUROREPORT LA English DT Article DE cortical inhibition; cortical silent period; GABA; neurophysiology; P50 suppression; schizophrenia ID TRANSCRANIAL MAGNETIC STIMULATION; NEUROPHYSIOLOGICAL DEFICIT; SCHIZOPHRENIA-PATIENTS; MOTOR CORTEX; INHIBITION; EXCITABILITY; HUMANS AB Deficient inhibitory neurotransmission has been demonstrated in schizophrenia through electroencephalography (e.g. P50 suppression) and transcranial magnetic stimulation (e.g. short-interval cortical inhibition and the cortical silent period). It is not known whether these inhibitory paradigms are related despite evidence suggesting that both are coordinated through gamma-aminobutyric acid inhibitory neurotransmission. We explored the relationship between P50 suppression, short-interval cortical inhibition and the cortical silent period in 21 healthy participants using previously published methods. P50 suppression was significantly correlated with cortical silent period (r=-0.49, P=0.02) but not with short-interval cortical inhibition. As both P50 suppression and the cortical silent period have been linked to gamma-aminobutyric acid(B) receptor-mediated inhibitory neurotransmission, these data highlight the importance of this receptor subtype in the pathophysiology of schizophrenia. C1 Univ Toronto, Ctr Addict & Mental Hlth, Schizophrenia Program, Toronto, ON M5T 1R8, Canada. Univ Toronto, Western Res Inst, Div Neurol, Toronto, ON, Canada. Univ Greifswald, Dept Psychiat, D-17487 Greifswald, Germany. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Boston, MA USA. Monash Univ, Psychiat Res Ctr, Dept Psychol Med, Clayton, Vic 3168, Australia. RP Daskalakis, ZJ (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, Schizophrenia Program, 250 Coll St,7th Floor, Toronto, ON M5T 1R8, Canada. EM Jeff_Daskalakis@camh.net RI Snyder, Joel/B-4675-2008; Chen, Robert/B-3899-2009; Daskalakis, Zafiris/J-5503-2013; Fitzgerald, Paul/A-1225-2008 OI Snyder, Joel/0000-0002-5565-3063; Chen, Robert/0000-0002-8371-8629; Daskalakis, Zafiris/0000-0001-9502-0538; Fitzgerald, Paul/0000-0003-4217-8096 NR 22 TC 6 Z9 6 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 17 PY 2007 VL 18 IS 14 BP 1503 EP 1506 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 210UA UT WOS:000249479900019 PM 17712283 ER PT J AU Evans, CL Xu, XY Kesari, S Xie, XS Wong, STC Young, GS AF Evans, Conor L. Xu, Xiaoyin Kesari, Santosh Xie, X. Sunney Wong, Stephen T. C. Young, Geoffrey S. TI Chemically-selective imaging of brain structures with CARS microscopy SO OPTICS EXPRESS LA English DT Article ID RAMAN SCATTERING MICROSCOPY; MULTIPLE-SCLEROSIS; LIVING CELLS; IN-VIVO; TISSUES; MICROSPECTROSCOPY; DIFFERENTIATION; TUMOR AB We demonstrate the use of coherent anti-Stokes Raman scattering ( CARS) microscopy to image brain structure and pathology ex vivo. Although non-invasive clinical brain imaging with CT, MRI and PET has transformed the diagnosis of neurologic disease, definitive pre-operative distinction of neoplastic and benign pathologies remains elusive. Definitive diagnosis still requires brain biopsy in a significant number of cases. CARS microscopy, a nonlinear, vibrationally-sensitive technique, is capable of high-sensitivity chemically-selective three-dimensional imaging without exogenous labeling agents. Like MRI, CARS can be tuned to provide a wide variety of possible tissue contrasts, but with sub-cellular spatial resolution and near real time temporal resolution. These attributes make CARS an ideal technique for fast, minimally invasive, non-destructive, molecularly specific intraoperative optical diagnosis of brain lesions. This promises significant clinical benefit to neurosurgical patients by providing definitive diagnosis of neoplasia prior to tissue biopsy or resection. CARS imaging can augment the diagnostic accuracy of traditional frozen section histopathology in needle biopsy and dynamically define the margins of tumor resection during brain surgery. This report illustrates the feasibility of in vivo CARS vibrational histology as a clinical tool for neuropathological diagnosis by demonstrating the use of CARS microscopy in identifying normal brain structures and primary glioma in fresh unfixed and unstained ex vivo brain tissue. (c) 2007 Optical Society of America. C1 Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Funct & Mol Imaging Ctr, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Neurol, Boston, MA 02115 USA. Methodist Hosp, Weill Cornell Med Coll, Ctr Bioinformat, Res Inst,Dept Radiol, Houston, TX 77030 USA. Brigham & Womens Hosp, Dept Radiol, Neuroradiol Sect, Boston, MA 02115 USA. RP Young, GS (reprint author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. EM gsyoung@partners.org RI Kesari, Santosh/E-8461-2013 NR 29 TC 137 Z9 139 U1 1 U2 37 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 17 PY 2007 VL 15 IS 19 BP 12076 EP 12087 DI 10.1364/OE.15.012076 PG 12 WC Optics SC Optics GA 218HK UT WOS:000250006400035 PM 19547572 ER PT J AU Hirshfeld-Becker, DR Biederman, J Henin, A Faraone, SV Micco, JA van Grondelle, A Henry, B Rosenbaum, JF AF Hirshfeld-Becker, Dina R. Biederman, Joseph Henin, Aude Faraone, Stephen V. Micco, Jamie A. van Grondelle, Anne Henry, Brianne Rosenbaum, Jerrold F. TI Clinical outcomes of laboratory-observed preschool behavioral disinhibition at five-year follow-up SO BIOLOGICAL PSYCHIATRY LA English DT Article DE behavioral disinhibition; children; disruptive behavior disorders; mood disorders; psychopathology; temperament ID AGE 3 YEARS; BIPOLAR DISORDER; LONGITUDINAL EVIDENCE; ANTISOCIAL-BEHAVIOR; INHIBITORY CONTROL; CONDUCT DISORDER; YOUNG-CHILDREN; PANIC DISORDER; BIRTH COHORT; CHILDHOOD AB Background: Behavioral disinhibition refers to a temperamental tendency to exhibit boldness, approach, and spontaneity in unfamiliar situations. We previously found it to be associated with childhood disruptive behavior and mood disorders, as well as with parental bipolar disorder. In the present study, our objective was to examine the diagnostic outcome in middle childhood of behavioral disinhibition assessed at preschool age among offspring at risk for anxiety and mood disorders. Methods: The sample consisted of 284 children, including offspring of parents with panic disorder or major depression and comparison offspring of parents without these disorders, who had been assessed with laboratory observations of temperament at ages 21 months to 6 years. We reassessed 215 of the children (77%) at 5-year follow-up (mean age 9.6 years) with structured diagnostic interviews. Results: Compared with noninhibited, nondisinhibited control subjects, behaviorally disinhibited children had higher lifetime rates of comorbid mood plus disruptive behavior disorders and higher current rates of any disruptive behavior disorder and of oppositional defiant disorder. Conclusions: Behavioral disinhibition appears to be a temperamental antecedent of disruptive behavior disorders and their comorbidity with mood disorders in middle childhood, which may be targeted for preventive intervention. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. SUNY Syracuse, Dept Psychiat, Syracuse, NY USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Program, 185 Alewife Brook Parkway, Cambridge, MA 02138 USA. EM dhirshfeld@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH 47077-11A, R01 MH047077, R01 MH047077-14] NR 63 TC 17 Z9 17 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2007 VL 62 IS 6 BP 565 EP 572 DI 10.1016/j.biopsych.2006.10.021 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 209RD UT WOS:000249404800003 PM 17306774 ER PT J AU Kim, YM Choi, YD Weissleder, R Tung, CH AF Kim, Youngmi Choi, Yongdoo Weissleder, Ralph Tung, Ching-Hsuan TI Membrane permeable esterase-activated fluorescent imaging probe SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE esterase; fluorescent; imaging probe ID CELLS; NEURONS AB An esterase- triggered probe 2 derived from a cyanine-based pH sensitive dye was developed for cell labeling. Permeation of probe 2 into cells and subsequent hydrolytic activation by cellular esterases result in a bright fluorescent intracellular signal. (c) 2007 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Weill Cornell Med Coll, Methodist Hosp, Dept Radiol, 6565 Fannin St,B5-022, Houston, TX 77030 USA. EM ctung@tnihs.org OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R33 CA114149-02, P50 CA086355, P50-CA86355, R01 CA099385, R01 CA099385-04, R33 CA114149] NR 15 TC 18 Z9 18 U1 6 U2 27 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD SEP 15 PY 2007 VL 17 IS 18 BP 5054 EP 5057 DI 10.1016/j.bmcl.2007.07.026 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 211FY UT WOS:000249510900008 PM 17664067 ER PT J AU Parekh, S Polo, JM Shaknovich, R Juszczynski, P Lev, P Ranuncolo, SM Yin, Y Klein, U Cattoretti, G Favera, RD Shipp, MA Melnick, A AF Parekh, Samir Polo, Jose M. Shaknovich, Rita Juszczynski, Przemyslaw Lev, Paola Ranuncolo, Stella M. Yin, Yingnan Klein, Ulf Cattoretti, Giorgio Favera, Riccardo Dalla Shipp, Margaret A. Melnick, Ari TI BCL6 programs lymphoma cells for survival and differentiation through distinct biochemical mechanisms SO BLOOD LA English DT Article ID CENTER B-CELLS; GERMINAL-CENTER FORMATION; EXPRESSION; REPRESSION; PROTOONCOGENE; INFLAMMATION; COREPRESSOR; BLIMP-1; PROTEIN; DOMAIN AB The BCL6 transcriptional repressor is the most commonly involved oncogene in diffuse large B-cell lymphomas (DLBCLs). Constitutive expression of BCL6 mediates lymphomagenesis through aberrant proliferation, survival, and differentiation blockade. Binding of BCL6 to the SMRT/N-CoR corepressors mediates the BCL6 survival effect in DLBCL. Although the basis for differentiation blockade is unknown in DLBCL, recent data suggest that BCL6 binding to the MTA3 corepressor might be involved. We report that BCL6 and MTA3 are coexpressed in nor-mal germinal center B cells and DLBCL. Depletion of MTA3 in DLBCL cells induced a differentiation-related BCL6 target gene (PRDM1), but not target genes involved in survival. Accordingly, MTA3 and PRDM1 expression are mutually exclusive in germinal center B cells. We performed chromatin immunoprecipitation (ChIP)-on-chip mapping of the PRDM1 locus, identifying a novel BCL6 binding site on intron 3 of the PRDM1 gene, and show that BCL6 recruits MTA3 to this site. In DLBCL cells, MTA3 depletion induced plasmacytic differentiation but did not decrease viability of DLBCL cells. However, MTA3 depletion synergized with a specific BCL6 inhibitor that blocks SMRT/N-CoR binding to decrease DLBCL viability. Taken together, these results show that BCL6 regulates distinct transcriptional programs through the SMRT/N-CoR and MTA3 corepressors, respectively, and provides a basis for combinatorial therapeutic targeting of BCL6. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Columbia Univ, Inst Canc Genet, New York, NY USA. Univ Milan, Monza, Italy. RP Melnick, A (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Chanin 302A, Bronx, NY 10461 USA. EM amelnick@aecom.yu.edu OI Cattoretti, Giorgio/0000-0003-3799-3221 FU NCI NIH HHS [R01 CA104348] NR 33 TC 84 Z9 86 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2007 VL 110 IS 6 BP 2067 EP 2074 DI 10.1182/blood-2007-01069575 PG 8 WC Hematology SC Hematology GA 213MM UT WOS:000249671700054 PM 17545502 ER PT J AU Cheng, J Kydd, AR Nakase, K Noonan, KM Murakami, A Tao, H Dwyer, M Xu, C Zhu, Q Marasco, WA AF Cheng, Jihua Kydd, Andre R. Nakase, Koichi Noonan, Kristin M. Murakami, Akikazu Tao, Hong Dwyer, Markryan Xu, Chen Zhu, Quan Marasco, Wayne A. TI Negative regulation of the SH2-homology-containing protein-tyrosine phosphatase-1 (SHP-1) P2 promoter by the HTLV-1 Tax oncoprotein SO BLOOD LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; NF-KAPPA-B; LONG TERMINAL REPEAT; TYPE-1 TAX; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVITY; ACTIVATES TRANSCRIPTION; RETINOBLASTOMA PROTEIN; JAK/STAT PROTEINS AB Expression of SH2-homology-containing protein-tyrosine phosphatase-1 (SHP-1), a candidate tumor suppressor, is repressed in human T-cell leukemia virus type-1 (HTLV-1)-transformed lymphocyte cell lines, adult T-cell leukemia (ATL) cells, and in other hematologic malignancies. However, the mechanisms underlying regulation and repression of SHP-1 remain unclear. Herein, we cloned the putative full-length, hematopoietic cell-specific SHP-1 P2 promoter and identified the "core" promoter regions. HTLV-1 Tax profoundly represses P2 promoter activity and histone deacetylase-1 (HDAC1) potentiates such inhibition. NF-kappa B was implicated as both a rate-limiting factor for basal P2 promoter activity and important for Tax-induced promoter silencing (TIPS). Chromatin immunoprecipitation studies demonstrated that NF-kappa B dissociates from the SHP-1 P2 promoter following the binding of Tax and HDAC1. This is in agreement with coimmunoprecipitation studies where NF-kappa B competed with HDAC1 for association with Tax protein. We propose that in TIPS, Tax recruits HDACII to the SHP-1 P2 promoter and forms an inhibitory complex that results in deacetylation and dissociation of NF-kappa B from the promoter and attenuation of SHP-1 expression. TIPS provides a possible first step toward HTLV-1 leukemogenesis through its down-modulation of this key immediate early negative regulator of IL-2 signaling. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.edu FU NCI NIH HHS [R01 CA104936, CA104936]; NIAID NIH HHS [AI058804, R21 AI058804] NR 82 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2007 VL 110 IS 6 BP 2110 EP 2120 DI 10.1182/blood-2006-11-058388 PG 11 WC Hematology SC Hematology GA 213MM UT WOS:000249671700059 PM 17540846 ER PT J AU Bilimoria, KY Bentrem, DJ Ko, CY Tomlinson, JS Stewart, AK Winchester, DP Talamonti, MS AF Bilimoria, Karl Y. Bentrem, David J. Ko, Clifford Y. Tomlinson, James S. Stewart, Andrew K. Winchester, David P. Talamonti, Mark S. TI Multimodality therapy for pancreatic cancer in the US - Utilization, outcomes, and the effect of hospital volume SO CANCER LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Society-of-Clinical-Oncology-Gastrointestinal Cancers CY JAN 19-21, 2007 CL Orlando, FL SP Amer Soc Clin Oncol Gastrointestinal Canc DE pancreatic neoplasms; surgery; chemotherapy; radiation therapy; multimodality therapy; National Cancer Data Base ID LONG-TERM SURVIVAL; OPERATIVE MORTALITY; CURATIVE RESECTION; CONSECUTIVE PANCREATICODUODENECTOMIES; ADJUVANT CHEMOTHERAPY; GENERAL-POPULATION; COLORECTAL-CANCER; RADIATION-THERAPY; LAST DECADE; ADENOCARCINOMA AB BACKGROUND. Despite decreased perioperative morbidity and mortality and clinical trials suggesting improved outcomes with adjuvant therapy, national practice patterns in the management of pancreatic cancer remain poorly defined. The purpose of the current study was to evaluate multimodality therapy utilization and outcomes relative to hospital type and Volume. METHODS. Using the National Cancer Data Base, stage-specific treatment patterns were analyzed for 301,033 patients with pancreatic adenocarcinoma. Logistic regression was used to evaluate treatment utilization. Cox proportional hazards modeling was utilized to evaluate the effect of multimodality therapy on survival. RESULTS. Stage at presentation did not differ from 1985-1994 to 1995-2003; however, the percentage of patients receiving cancer-directed treatment increased from 45.1% to 51.8% (P < .001). Pancreatectomy for localized disease (AJCC 6th edition stages I and 11) increased from 36.9% to 49.3% (P < .001). After resection, the use of adjuvant chemotherapy alone increased from 4.1% to 5.7% (P < .001), but the use of adjuvant radiation alone decreased from 7.0% to 4.6% (P < .001). Adjuvant chemoradiation use increased from 26.8% to 38.7% (P < .001). The use Of Surgery alone decreased from 62.1% (5213 of 8400 cases) to 49.9% (10,807 of 21,679 cases) (P < .001), Patients with localized pancreatic cancer were more likely to receive pancreatectomy and adjuvant chemoradiation at academic and high-volume centers (P < .001). Survival for localized disease was better after surgery with adjuvant therapy (hazards ratio [HR], 0.44; 95% confidence interval [95% CI], 0.42-0.47) and surgical resection alone (HR, 0.54; 95% CI, 0.52-0.57) compared with no treatment. CONCLUSIONS. To the authors' knowledge, the current study is the largest study regarding pancreatic cancer performed to date, and the first to investigate national practice patterns for multimodality therapy utilization. Multimodality therapy utilization has increased over time and appears to have a beneficial impact on survival. C1 Northwestern Univ, Feinburg Sch Med, Div Surg Oncol, Dept Surg, Chicago, IL 60611 USA. Amer Coll Surg, Natl Canc Data Base, Canc Programs, Chicago, IL USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Evanston NW Hosp, Dept Surg, Evanston, IL USA. RP Talamonti, MS (reprint author), Northwestern Univ, Feinburg Sch Med, Div Surg Oncol, Dept Surg, 675 N St Clair St,Galter 10-105, Chicago, IL 60611 USA. EM mtalamonti@nmff.org NR 53 TC 104 Z9 108 U1 0 U2 4 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 2007 VL 110 IS 6 BP 1227 EP 1234 DI 10.1002/cncr.22916 PG 8 WC Oncology SC Oncology GA 208FA UT WOS:000249304000008 PM 17654662 ER PT J AU Cortes, J Jabbour, E Daley, GQ O'Brien, S Verstovsek, S Koller, C Zhu, Y Statkevich, P Kantarjian, H AF Cortes, Jorge Jabbour, Elias Daley, George Q. O'Brien, Susan Verstovsek, Srdan Koller, Charles Zhu, Yali Statkevich, Paul Kantarjian, Hagop TI Phase 1 study of lonafarnib (SCH 66336) and imatinib mesylate in patients with chronic myeloid leukemia who have failed prior single-agent therapy with imatinib SO CANCER LA English DT Article DE lonafarnib; imatinib; chronic myeloid leukemia; phase 1 study; farnesyl transferase inhibitor ID FARNESYL TRANSFERASE INHIBITOR; CHRONIC MYELOGENOUS LEUKEMIA; CHROMOSOME-POSITIVE LEUKEMIAS; DASATINIB BMS-354825; INTERFERON-ALPHA; IN-VITRO; PROTEIN TRANSFERASE; MOLECULAR RESPONSES; CLINICAL ACTIVITY; KINASE INHIBITOR AB BACKGROUND. Lonafarnib is an orally bioavailable nonpetidomimetic farnesyl transferase inhibitor with significant activity against BCR-ABL-positive cell lines and primary human chronic myeloid leukemia (CML) cells. Lonafarnib can inhibit the proliferation of imatinib-resistant cells and increases imatinib-induced apoptosis in vitro in cells from imatinib-resistant patients. METHODS. The authors conducted a phase I study of lonafarnib in combination with imatinib in patients with CML who failed imatinib therapy. The starting dose level for patients with chronic phase (CP) disease was imatinib, 400 mg/day,plus lonafarnib at a dose of 100 mg twice daily. The starting dose levels for accelerated phase (AP) and blast phase (BP) disease were 600 mg/day and 100 mg twice daily, respectively. RESULTS. A total of 23 patients were treated (9 with CP 11 with AP, and 3 with BP) for a median of 25 weeks (range, 4-102 weeks). Of those with CP disease, 2 patients had grade 3 (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) dose-limiting toxicities (DLTs) at the 400 + 125-mg dose, including diarrhea (2 patients), vomiting (1 patient), and fatigue (I patient). In patients with AP/BP disease, DLTs were observed at the 600 + 125-mg dose and was comprised of diarrhea (1 patient) and hypokalemia (1 patient). Eight patients (35%) responded; 3 with CP disease achieved a complete hematologic response (CHR) (2 patients) and a complete cytogenetic response (1 patient). Three patients with AP disease responded (2 CHR, 1 partial cytogenetic response), and 2 patients with BP disease demonstrated hematologic improvement. Pharmacokinetics data suggest no apparent increase in exposure or changes in the pharmacokinetics of either lonafarnib or imatinib when they are coadministered. CONCLUSIONS. The results of the current study indicate that the combination of lonafarnib and imatinib is well tolerated and the maximum tolerated dose of lonafarnib is 100 mg twice daily when combined with imatinib at a dose of either 400 mg or 600 mg daily. C1 Univ Texas, MD Anderson Canc Ctr, DEpt Leukemia, Houston, TX 77030 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Cortes, J (reprint author), Univ Texas, MD Anderson Canc Ctr, DEpt Leukemia, 1515 Holcombe Blvd,Box 428, Houston, TX 77030 USA. EM jcortes@mdanderson.org NR 46 TC 32 Z9 35 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 2007 VL 110 IS 6 BP 1295 EP 1302 DI 10.1002/cncr.22901 PG 8 WC Oncology SC Oncology GA 208FA UT WOS:000249304000017 PM 17623836 ER PT J AU Faber, J Armstrong, SA AF Faber, Joerg Armstrong, Scott A. TI Mixed lineage leukemia translocations and a leukemia stem cell program SO CANCER RESEARCH LA English DT Review ID ACUTE MYELOID-LEUKEMIA; BRAIN-TUMORS; IDENTIFICATION; PROGENITORS; CANCER; TRANSFORMATION; MLL-AF9; GENE; MICE AB Cancer stem cells (CSC) may provide the self-renewal capacity required to sustain a tumor. One possibility is that CSC arise from the stem cell counterparts in normal tissues. Alternatively, CSC may arise from more differentiated progenitor cells found in certain tissues. In support of this idea, we showed recently that mixed lineage leukemia fusion oncoproteins can convert committed hematopoietic progenitors into leukemias, which include leukemia stem cells expressing a self-renewal associated program in the context of a differentiated myeloid cell. The findings suggest a basis to understand the pathobiology of CSC and possible strategies to attack them to undermine the self-renewal capacity of a tumor. C1 Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Armstrong, SA (reprint author), Childrens Hosp, Karp Family Res Labs, 1 Blackfan Circle, Boston, MA 02115 USA. EM Scott.Armstrong@childrens.harvard.edu NR 24 TC 8 Z9 8 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2007 VL 67 IS 18 BP 8425 EP 8428 DI 10.1158/0008-5472.CAN-07-0972 PG 4 WC Oncology SC Oncology GA 213PL UT WOS:000249679500001 PM 17875678 ER PT J AU Wang, F Sloss, C Zhang, X Lee, SW Cusack, JC AF Wang, Fang Sloss, Callum Zhang, Xiaobo Lee, Sam W. Cusack, James C. TI Membrane-bound heparin-binding epidermal growth factor-like growth factor regulates E-cadherin expression in pancreatic carcinoma cells SO CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITIONS; REPRESSES E-CADHERIN; HB-EGF; DOWN-REGULATION; CANCER; LINES; SENSITIVITY; SNAIL; METASTASIS; ACTIVATION AB Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF growth factor family. Initially synthesized as a membrane-bound precursor (pro-HB-EGF), it is cleaved at the juxtamembrane domain to release the soluble form of HB-EGF (s-HB-EGF) by sheddases, including matrix metalloproteinases (MMP) and a disintegrin and metalloproteinases. This is a process referred to as ectodomain shedding and is implicated in the process of all ligands of the EGF receptor (EGFR) family. The tumorigenic potential of s-HB-EGF has been studied extensively; however, the role of pro-HB-EGF in tumor progression is unknown, despite the fact that a considerable amount of pro-HB-EGF remains on the cell membrane. Our data here clearly indicated the distinct role of pro-HB-EGF in the regulation of E-cadherin expression and the epithelial-mesenchymal transition. We showed here that the expression of pro-HB-EGF was associated with the differentiation status in pancreatic tumors and cell lines. Expression of noncleaved pro-HB-EGF in pancreatic cells resulted in the up-regulation of E-cadherin through suppression of ZEB1, which is a transcriptional repressor of E-cadherin. Inhibition of HB-EGF shedding using a MMP inhibitor, GM6001, also dramatically augmented the E-cadherin expression while suppressing the EGFR activation. Moreover, up-regulation of E-cadherin by pro-HB-EGF not only resulted in cellular morphologic change but also decreased cell motility and enhanced apoptotic sensitivity in response to gemcitabine-erlotinib treatment. Collectively, our data defined a distinct role of pro-HB-EGF in the regulation of E-cadherin, suggesting that inhibition of shedding may be a novel approach to suppress pancreatic metastasis and sensitize cells to cancer therapy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Gastrointestinal Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Cusack, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Surg Oncol, 7th Floor,yawkey Bldg 55 Fruit St, Boston, MA 02114 USA. EM fwang6@partners.org; jcusack@partners.org FU NCI NIH HHS [CA98871-01, CA77278-01A1] NR 38 TC 32 Z9 32 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2007 VL 67 IS 18 BP 8486 EP 8493 DI 10.1158/0008-5472.CAN-07-0498 PG 8 WC Oncology SC Oncology GA 213PL UT WOS:000249679500011 PM 17875687 ER PT J AU Seng, S Avraham, HK Jiang, SX Yang, SP Sekine, M Kimelman, N Li, H Avraham, S AF Seng, Seyha Avraham, Hava Karsenty Jiang, Shuxian Yang, Suping Sekine, Masayuki Kimelman, Noam Li, Huchun Avraham, Shalom TI The nuclear matrix protein, NRP/B, enhances Nrf2-mediated oxidative stress responses in breast cancer cells SO CANCER RESEARCH LA English DT Article ID ELEMENT-MEDIATED EXPRESSION; HUMAN BRAIN-TUMORS; GENE-EXPRESSION; DT-DIAPHORASE; HYDROGEN-PEROXIDE; DNA-DAMAGE; INDUCTION; NRF2; ACTIVATION; DROSOPHILA AB The transcription factor NF-E2-related factor 2 (Nrf2) translocates into the nucleus and activates phase 11 genes encoding detoxification enzymes and antioxidant proteins, resulting in the protection of cells from oxidative insults. However, the involvement of Nrf2-mediated oxidative stress responses in breast cancer cells is largely unknown. Notably, during our study of the Nrf2 pathway in breast cancer cells, we observed that the nuclear matrix protein NRP/B was expressed and colocalized with Nrf2 in these cells, suggesting that NRP/B is involved in Nrf2-mediated oxidative stress responses. The expression level of NRP/B was variable in different breast cancer cells and breast cancer tissues, and was found to be localized in the nucleus. NRP/B expression was increased after exposure to the oxidative stress agent, hydrogen peroxide (H2O2), particularly in the highly aggressive MDA-MB-231 breast cancer cells. Association of NRP/B with Nrf2 in vitro and in vivo was observed in MDA-MB-231 breast cancer cells, and this association was up-regulated upon exposure to H2O2, but not to sodium nitroprusside, SIN-1, and DETA-NO. NRP/B also enhanced Nrf2-mediated NAD(P)H:qujnine oxidoreductase I promoter activity. Thus, this study reveals that NRP/B enhances oxidative stress responses in breast cancer cells via the Nrf2 pathway, identifying a novel role of nuclear matrix protein(s) in oxidative stress responses. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Avraham, S (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Inst Med, Div Expt Med, 4 Blackfan Circle, Boston, MA 02215 USA. EM savraham@bidmc.harvard.edu FU NCI NIH HHS [CA096805]; NHLBI NIH HHS [HL80699] NR 43 TC 13 Z9 16 U1 2 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 2007 VL 67 IS 18 BP 8596 EP 8604 DI 10.1158/0008-5472.CAN-06-3785 PG 9 WC Oncology SC Oncology GA 213PL UT WOS:000249679500024 PM 17875699 ER PT J AU Kwak, EL Clark, JW Chabner, B AF Kwak, Eunice L. Clark, Jeffrey W. Chabner, Bruce TI Targeted agents: The rules of combination SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; RENAL-CELL CARCINOMA; BREAST-CANCER CELLS; METASTATIC COLORECTAL-CANCER; LUNG-CANCER; INTERFERON-ALPHA; PLUS IRINOTECAN; PHASE-II; INHIBITION; MUTATIONS AB The success of molecularly targeted agents (MTA) in the treatment of cancer has led to the investigation of their use in combination with other MTAs and with conventional chemotherapies. An overview of the MTAs that have emerged as Food and Drug Administration -approved drugs is presented, along with a framework for the consideration of how MTAs can best be combined to maximize therapeutic effect. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Kwak, EL (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Profess Off Bldg, Boston, MA 02114 USA. EM ekwak@partners.org NR 49 TC 35 Z9 36 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 2007 VL 13 IS 18 BP 5232 EP 5237 DI 10.1158/1078-0432.CCR-07-1385 PN 1 PG 6 WC Oncology SC Oncology GA 214JV UT WOS:000249734700003 PM 17875749 ER PT J AU Hodi, FS AF Hodi, F. Stephen TI Cytotoxic T-Lymphocyte - Associated antigen-4 SO CLINICAL CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; PHASE-I TRIAL; METASTATIC MELANOMA; CTLA-4 BLOCKADE; COMBINATION IMMUNOTHERAPY; PROSTATE-CANCER; MONOCLONAL-ANTIBODY; INHIBITORY SIGNALS; TRANSGENIC MOUSE; TUMOR-REGRESSION AB Previously, the development of immune-based therapies has primarily focused on vaccines and cytokines, yielding benefit in a small percentage of patients. Recent advances in our understanding of the function of costimulatory molecules have revitalized enthusiasm in the development of immune therapies for cancer. This family of proteins possesses properties involved in both lymphocyte activation and immune- inhibitory functions. The costimulatory molecule with the greatest translation into the clinic thus far is CTL-associated antigen-4 (CTLA-4). CTLA-4 engagement leads to T-cell inhibition by two principle mechanisms. The first involves competitive binding with CD28 for B7 on the antigen -presenting cell. The second is direct intracellular inhibitory signals mediated by the CTLA-4 cytoplasmic tail. Numerous clinical trials testing the blockade of CTLA-4 signaling with fully human monoclonal antibodies have treated a variety of cancers, with the most experience in the treatment of metastatic melanoma. Significant antitumor activity as well as potential autoimmune-related toxicities have been observed. Further clinical investigation with CTLA-4 blockade, planned clinical trials testing manipulation of other costimulatory molecules, and continued improvement in understanding of costimulatory pathways present a new era of immune therapies for cancer patients. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM stephen_hodi@dfci.harvard.edu NR 43 TC 45 Z9 52 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2007 VL 13 IS 18 BP 5238 EP 5242 DI 10.1158/1078-0432.CCR-07-0813 PN 1 PG 5 WC Oncology SC Oncology GA 214JV UT WOS:000249734700004 PM 17875750 ER PT J AU Desai, J Shankar, S Heinrich, MC Fletcher, JA Fletcher, CD Manola, J Morgan, J Corless, CL George, S Tuncali, K Silverman, SG Van den Abbeele, AD van Sonnenberg, E Demetri, GD AF Desai, Jayesh Shankar, Sridhar Heinrich, Michael C. Fletcher, Jonathan A. Fletcher, Christopher D. Manola, Judi Morgan, JeffreyA. Corless, Christopher L. George, Suzanne Tuncali, Kemal Silverman, Stuart G. Van den Abbeele, Annick D. van Sonnenberg, Eric Demetri, George D. TI Clonal evolution of resistance to imatinib in patients with metastatic gastrointestinal stromal tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITOR; OF-FUNCTION MUTATIONS; C-KIT; ACQUIRED-RESISTANCE; EMISSION-TOMOGRAPHY; INTERSTITIAL-CELLS; PHASE-I; MESYLATE; GENE; ONCOLOGY AB Purpose: Resistance to imatinib mesylate is emerging as a clinical challenge in patients with metastatic gastrointestinal stromal tumors (GIST). Novel patterns of progression have been noted in a number of these patients. The objective of this study was to correlate molecular and radiologic patterns of imitinib-refractory disease with existing conventional criteria for disease progression. Experimental Design: Patients with metastatic GIST treated with imatinib were followed with serial computed tomography/magnetic resonance imaging and [F-18]fluoro-2-deoxy-D-glucose positron emission tomography. Where feasible, biopsies were done to document disease progression. Results: A total of 89 patients were followed for a median of 43 months. Forty-eight patients developed progressive disease. A unique "resistant clonal nodule" pattern (defined as a new enhancing nodular focus enclosed within a preexisting tumor mass) was seen in 23 of 48 patients and was thought to represent emergence of clones resistant to imatinib. Nodules were demonstrable a median of 5 months (range, 0-13 months) before objective progression defined by tumor size criteria and were the first sign of progression in 18 of 23 patients. Median survival among patients whose first progression was nodular was 35.1 months, compared with 44.6 months for patients whose first progression met Southwest Oncology Group criteria (P = 0.31). Comparative tumor biopsies were done in 10 patients at baseline and from progressing nodules. Genotypic analyses of KIT and PDGFRA kinases were done, revealing new activating kinase mutations in 80% (8 of 10) of these patients. Conclusion: The resistant clonal nodule is a unique pattern of disease progression seen in patients with GISTs after an initial response to imatinib and reflects the emergence of imatinib-resistant clones. Conventional tumor measurements (Southwest Oncology Group/Response Evaluation Criteria in Solid Tumors) do not detect this subtle finding. A new enhancing nodule growing within a preexisting tumor mass should be classified as a new lesion and be regarded, at least, as partial progression of GIST. C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, SW530,44 Binney St, Boston, MA 02115 USA. EM george-demetri@dfci.harvard.edu NR 47 TC 65 Z9 68 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 2007 VL 13 IS 18 BP 5398 EP 5405 DI 10.1158/1078-0432.CCR-06-0858 PN 1 PG 8 WC Oncology SC Oncology GA 214JV UT WOS:000249734700026 PM 17875769 ER PT J AU Steffen, LS Guyon, JR Vogel, ED Howell, MH Zhou, Y Weber, GJ Zon, LI Kunkel, LM AF Steffen, Leta S. Guyon, Jeffrey R. Vogel, Emily D. Howell, Melanie H. Zhou, Yi Weber, Gerhard J. Zon, Leonard I. Kunkel, Louis M. TI The zebrafish runzel muscular dystrophy is linked to the titin gene SO DEVELOPMENTAL BIOLOGY LA English DT Article DE titin; muscular dystrophy; titinopathy; birefringence; zebrafish; zebrafish muscle; sarcomere ID DILATED CARDIOMYOPATHY; ISOFORM EXPRESSION; IMMUNOELECTRON MICROSCOPY; SKELETAL-MUSCLE; KINASE DOMAIN; Z-DISC; Z-LINE; PROTEIN; STIFFNESS; MYOCARDIUM AB Titin (also called connectin) acts as a scaffold for signaling proteins in muscle and is responsible for establishing and maintaining the structure and elasticity of sarcomeres in striated muscle. Several human muscular dystrophies and cardiomyopathies have previously been linked to mutations in the titin gene. This study reports linkage of the runzel homozygous lethal muscular dystrophy in the zebrafish Danio rerio to a genomic interval containing the titin gene. Analysis of the genomic sequence suggests that zebrafish contain two adjacent titin loci. One titin locus lies within the genetic linkage interval and its expression is significantly reduced in runzel mutants by both immunofluorescence and protein electrophoresis. Morpholino downregulation of this same titin locus in wild-type embryos results in decreased muscle organization and mobility, phenocopying runzel mutants. Additional protein analysis demonstrates that, in wild-type zebrafish, titin isoform sizes are rapidly altered during the development of striated muscle, likely requiring a previously unrecognized need for vertebrate sarcomere remodeling to incorporate developmentally regulated titin isoforms. Decreases of affected titin isoforms in runzel mutants during this time correlate with a progressive loss of sarcomeric organization and suggest that the unaffected titin proteins are capable of sarcomerogenesis but not sarcomere maintenance. In addition, microarray analysis of the ruz transcriptome suggests a novel mechanism of dystrophy pathogenesis, involving mild increases in calpain-3 expression and upregulation of heat shock proteins. These studies should lead to a better understanding of titin's role in normal and diseased muscle. (C) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Program Genom, Boston, MA 02115 USA. Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Steffen, LS (reprint author), Harvard Univ, Sch Med, Dept Genet, 300 Longwood Ave, Boston, MA 02115 USA. EM lsteffen@gmail.com FU NICHD NIH HHS [P30 HD018655, P30-HD18655]; NINDS NIH HHS [P01 NS040828, P01 NS040828-06A1] NR 43 TC 29 Z9 29 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 2007 VL 309 IS 2 BP 180 EP 192 DI 10.1016/j.ydbio.2007.06.015 PG 13 WC Developmental Biology SC Developmental Biology GA 211IO UT WOS:000249517700003 PM 17678642 ER PT J AU Shen, LL Jin, YP Freeman, GJ Sharpe, AH Dana, MR AF Shen, Linling Jin, Yiping Freeman, Gordon J. Sharpe, Arlene H. Dana, M. Reza TI The function of donor versus recipient programmed death ligand 1 in corneal allograft survival SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-ACTIVATION; ANTIGEN-PRESENTING CELLS; ENDOTHELIAL-CELLS; IMMUNE PRIVILEGE; DENDRITIC CELLS; B7 FAMILY; MICE; EXPRESSION; REJECTION; PATHWAY AB Programmed death-ligand (PD-L)1 and PD-L2, newer B7 superfamily members, are implicated in the negative regulation of immune responses and peripheral tolerance. To examine their function in alloimmunity, we used the murine model of orthotopic corneal transplantation. We demonstrate that PD-L1, but not PD-L2, is constitutively expressed at high levels by the corneal epithelial cells, and at low levels by corneal CD45(+) cells in the stroma, whereas it is undetectable on stromal fibroblasts and corneal endothelial cells. Inflammation induces PD-L1 up-regulation by corneal epithelial cells, and infiltration of significant numbers of PD-L1(+)CD45(+)CD11b(+) cells. Blockade with anti-PD-L1 mAb dramatically enhances rejection of C57BL/6 corneal allografts by BALB/c recipients. To examine the selective contribution of donor vs host PD-L1 in modulating allorejection, we used PD-L1(-/-) mice as hosts or donors of combined MHC and minor H-mismatched corneal grafts. BALB/c grafts placed in PD-L1(-/-) C57BL/6 hosts resulted in pronounced T cell priming in the draining lymph nodes, and universally underwent rapid rejection. Allografts from PD-L1(-/-) C57BL/6 donors were also significantly more susceptible to rejection than wild-type C57BL/6 grafts placed into BALB/c hosts, primarily as a result of increased T cell infiltration rather than enhanced priming. Taken together, our results identify differential roles for recipient vs donor PD-L1 in regulating induction vs effector of alloimmunity in corneal grafts, the most common form of tissue transplantation, and highlight the importance of peripheral tissue-derived PD-L1 in down-regulating local immune responses. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. EM Reza.dana@schepens.harvard.edu FU NCRR NIH HHS [P20 RR20753]; NEI NIH HHS [R01-EY12963]; NIAID NIH HHS [AI39671, AI56299] NR 31 TC 48 Z9 50 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 2007 VL 179 IS 6 BP 3672 EP 3679 PG 8 WC Immunology SC Immunology GA 210ON UT WOS:000249465600036 PM 17785803 ER PT J AU Liu, D Lu, F Qin, G Fernandes, SM Li, J Davis, AE AF Liu, Dongxu Lu, Fengxin Qin, Gangjian Fernandes, Stacey M. Li, Jinan Davis, Alvin E., III TI C1 inhibitor-mediated protection from sepsis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; N-LINKED GLYCOSYLATION; SEPTIC SHOCK; ESTERASE INHIBITOR; C1-ESTERASE INHIBITOR; LEUKOCYTE ADHESION; DOUBLE-BLIND; PLASMA EXTRAVASATION; EXPERIMENTAL-MODEL; CONTROLLED-TRIAL AB C1 inhibitor (C1INH) protects mice from lethal Gram-negative bacterial LPS-induced endotoxin shock and blocks the binding of LPS to the murine macrophage cell line, RAW 264.7, via an interaction with lipid A. Using the cecal ligation and puncture (CLP) model for sepsis in mice, treatment with C1INH improved survival in comparison with untreated controls. The effect was not solely the result of inhibition of complement and contact system activation because reactive center-cleaved, inactive C1INH (iC1INH) also was effective. In vivo, C1INH and iC1INH both reduced the number of viable bacteria in the blood and peritoneal fluid and accelerated killing of bacteria by blood neutrophils and peritoneal macrophages. In vitro, C1INH bound to bacteria cultured from blood or peritoneal fluid of mice with CLP-induced sepsis, but had no direct effect on bacterial growth. However, both C1INH and iC1INH enhanced the bactericidal activity of blood neutrophils and peritoneal exudate leukocytes. C1INH-deficient mice (C1INH(-/-) mice) subjected to CLP had a higher mortality than did wild-type littermate mice. Survival of ClINH-/- mice was significantly increased with two doses of C1INH, one given immediately following CLP, and the second at 6 h post-CLP. C1INH may be important in protection from sepsis through enhancement of bacterial uptake by, and/or bactericidal capacity of, phagocytes. Treatment with C1INH may provide a useful additional therapeutic approach in some patients with peritonitis and/or sepsis. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Tufts Univ, Sch Med, Caritas St Elizabeths Med Ctr, Div Cardiovasc Res, Boston, MA 02135 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM dxliu@hubu.edu.cn; aldavis@cbrinstitute.org FU NIAID NIH HHS [AI057366]; NICHD NIH HHS [HD22082] NR 61 TC 36 Z9 45 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2007 VL 179 IS 6 BP 3966 EP 3972 PG 7 WC Immunology SC Immunology GA 210ON UT WOS:000249465600067 PM 17785834 ER PT J AU Banda, NK Takahashi, K Wood, AK Holers, VM Arend, WP AF Banda, Nirmal K. Takahashi, Kazue Wood, Allyson K. Holers, V. Michael Arend, William P. TI Pathogenic complement activation in collagen antibody-induced arthritis in mice requires amplification by the alternative pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FC-GAMMA RECEPTORS; RHEUMATOID-ARTHRITIS; II COLLAGEN; FACTOR-H; AUTOIMMUNE-DISEASE; IMMUNE-COMPLEXES; CLASSICAL PATHWAY; PASSIVE TRANSFER; SYNOVIAL TISSUE; FACTOR-B AB Immune complex-induced inflammation can be mediated by the classical pathway of complement. However, using mice genetically deficient in factor B or C4, we have shown that the collagen Ab-induced model of arthritis requires the alternative pathway of complement and is not dependent on the classical pathway. We now demonstrate that collagen Ab-induced arthritis is not altered in mice genetically deficient in either C1q or mannose-binding lectins A and C, or in both C1q and mannose-binding lectins. These in vivo results prove the ability of the alternative pathway to carry out pathologic complement activation in the combined absence of intact classical and lectin pathways. C3 activation was also examined in vitro by adherent collagen-anti-collagen immune complexes using sera from normal or complement-deficient mice. These results confirm the ability of the alternative pathway to mediate immune complex-induced C3 activation when C4 or C1q, or both C1q and mannose-binding lectins, are absent. However, when all three activation pathways of complement are intact, initiation by immune complexes occurs primarily by the classical pathway. These results indicate that the alternative pathway amplification loop, with its ability to greatly enhance C3 activation, is necessary to mediate inflammatory arthritis induced by adherent immune complexes. C1 Univ Colorado Denver, Hlth Sci Ctr, Div Rheumatol, Aurora, CO 80045 USA. Massachusetts Gen Hosp, Dev Immunol Pediat Serv, Boston, MA 02114 USA. RP Arend, WP (reprint author), Univ Colorado Denver, Hlth Sci Ctr, Div Rheumatol, B115,Bldg M20,Rm 3106,1775 N Ursula St, Aurora, CO 80045 USA. EM william.arend@uchsc.edu FU NIAMS NIH HHS [AR51749] NR 61 TC 59 Z9 60 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2007 VL 179 IS 6 BP 4101 EP 4109 PG 9 WC Immunology SC Immunology GA 210ON UT WOS:000249465600082 PM 17785849 ER PT J AU Hongo, D Hadidi, S Damrauer, S Garrigue, V Kraft, D Sachs, DH Nikolic, B Sykes, M AF Hongo, David Hadidi, Sima Damrauer, Scoff Garrigue, Valerie Kraft, Daniel Sachs, David H. Nikolic, Boris Sykes, Megan TI Porcine thymic grafts protect human thymocytes from HIV-1-induced destruction SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SCID-HU MOUSE; ACTIVE ANTIRETROVIRAL THERAPY; MHC CLASS-I; CORECEPTOR EXPRESSION; IMMUNE RESTORATION; EPITHELIAL-CELLS; HIV-INFECTION; VIRAL ENTRY; T-CELLS AB Human immunodeficiency virus type 1 (HIV-1) infection depletes thymocytes and destroys thymic structure. Functional, tolerant human T cells develop in vivo in immunodeficient mice receiving porcine thymus and human fetal fiver fragments under the kidney capsule. In this model, we evaluated the potential of porcine thymus to protect human thymocytes from the effects of HIV-1. Compared with that observed in control mice with human thymic grafts, porcine thymus attenuated human thymocyte depletion by the CCR5-tropic isolate JR-CSF without preventing thymocyte infection. Porcine thymus protected human thymocytes from infection and depletion by a CXCR4-tropic HIV-1 isolate without reducing peripheral blood viral loads or T cell infection. Human thymocytes from human but not porcine grafts showed decreased Bcl-2 expression and increased apoptosis after NL4.3 infection. Thus, porcine thymus protects human thymocytes from the cytopathic effect of HIV-1, suggesting a possible approach to achieving immune restoration in patients with acquired immunodeficiency syndrome who have incomplete responses to antiretroviral therapy. The model allows analysis of the mechanisms of HIV-mediated thymic dysfunction. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Biol Res Ctr,Bone Marrow Transplantat, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Biol Res Ctr,Bone Marrow Transplantat, MGH E Bldg,149-5102,13th St, Boston, MA 02129 USA. EM Megan.Sykes@tbrc.mgh.harvard.edu FU NIAID NIH HHS [P01 AI39755] NR 43 TC 4 Z9 4 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 SEP 15 PY 2007 VL 196 IS 6 BP 900 EP 910 DI 10.1086/520516 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 207LE UT WOS:000249251800015 PM 17703422 ER PT J AU Powers, KM Kay, DM Factor, SA Zabetian, CP Higgins, D Samii, A Nutt, JG Griffith, A Leis, B Roberts, JW Martinez, ED Montimurro, JS Checkoway, H Payami, H AF Powers, K. M. Kay, D. M. Factor, S. A. Zabetian, C. P. Higgins, D. Samii, A. Nutt, J. G. Griffith, A. Leis, B. Roberts, J. W. Martinez, E. D. Montimurro, J. S. Checkoway, H. Payami, H. TI Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 21st Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinsons Disease and Other Movement Disorders CY OCT 07, 2007 CL Washington, DC SP Parkinson Study Grp, Huntinton Study Grp, Dystonia Study Grp, Myoclonus Study Grp, Tourette Syndrome Study Grp, Cooperat Ataxia Grp, Tremor Res Grp, Movement Disorder Soc C1 Univ Washington, Sch Publ Hlth & Community Med, Dept Environm & Occupat Hlth, Seattle, WA 98195 USA. New York State Dept Hlth, Gen Inst, Albany, NY USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Va Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2007 VL 22 IS 12 BP II EP II PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 218CD UT WOS:000249992700037 ER PT J AU Sadri-Vakili, G Bouzou, B Benn, CL Kim, MO Chawla, P Overland, RP Glajch, KE Xia, E Qiu, Z Hersch, SM Clark, TW Yohrling, GJ Cha, JHJ AF Sadri-Vakili, G. Bouzou, B. Benn, C. L. Kim, M.-O. Chawla, P. Overland, R. P. Glajch, K. E. Xia, E. Qiu, Z. Hersch, S. M. Clark, T. W. Yohrling, G. J. Cha, J.-H. J. TI Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 21st Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinsons Disease and Other Movement Disorders CY OCT 07, 2007 CL Washington, DC SP Parkinson Study Grp, Huntinton Study Grp, Dystonia Study Grp, Myoclonus Study Grp, Tourette Syndrome Study Grp, Cooperat Ataxia Grp, Tremor Res Grp, Movement Disorder Soc C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA USA. MassGen Inst Neurodegenerat Dis, Ctr Interdisciplinary Informat, Charlestown, MA USA. Johnson & Johnson Pharmaceut, Res & Dev, LLC, Spring House, PA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2007 VL 22 IS 12 MA 2 BP IV EP V PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 218CD UT WOS:000249992700044 ER PT J AU Kim, MO Chawla, P Overland, RP Xia, E Sadri-Vakili, G Cha, JH AF Kim, M. O. Chawla, P. Overland, R. P. Xia, E. Sadri-Vakili, G. Cha, J. H. TI Mutant huntingtin-mediated histone monoubiquitylation induces transcriptional dysregulation in Huntington's disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 21st Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinsons Disease and Other Movement Disorders CY OCT 07, 2007 CL Washington, DC SP Parkinson Study Grp, Huntinton Study Grp, Dystonia Study Grp, Myoclonus Study Grp, Tourette Syndrome Study Grp, Cooperat Ataxia Grp, Tremor Res Grp, Movement Disorder Soc C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2007 VL 22 IS 12 MA 5 BP V EP V PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 218CD UT WOS:000249992700047 ER PT J AU Kim, HM Samii, A Martinez, E Richards, G Zabetian, C Leverenz, JB AF Kim, H. M. Samii, A. Martinez, E. Richards, G. Zabetian, C. Leverenz, J. B. TI The Washington Parkinson disease registry (WPDR): A state-wide research registry SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 21st Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinsons Disease and Other Movement Disorders CY OCT 07, 2007 CL Washington, DC SP Parkinson Study Grp, Huntinton Study Grp, Dystonia Study Grp, Myoclonus Study Grp, Tourette Syndrome Study Grp, Cooperat Ataxia Grp, Tremor Res Grp, Movement Disorder Soc C1 Univ Washington, Dept Neurol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, NW Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2007 VL 22 IS 12 MA 17 BP IX EP IX PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 218CD UT WOS:000249992700059 ER PT J AU Kim, HM Samii, A Factor, SA Griffith, A Roberts, J Mosley, AD Leis, BC Yearout, D Hutter, CM Edwards, KL Richards, G Nutt, JG Higgins, DS Payami, H Zabetian, CP AF Kim, H. M. Samii, A. Factor, S. A. Griffith, A. Roberts, Jw. Mosley, A. D. Leis, B. C. Yearout, D. Hutter, C. M. Edwards, K. L. Richards, G. Nutt, J. G. Higgins, D. S. Payami, H. Zabetian, C. P. TI HFE variants C282Y and H63D do not alter risk of Parkinson's disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 21st Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinsons Disease and Other Movement Disorders CY OCT 07, 2007 CL Washington, DC SP Parkinson Study Grp, Huntinton Study Grp, Dystonia Study Grp, Myoclonus Study Grp, Tourette Syndrome Study Grp, Cooperat Ataxia Grp, Tremor Res Grp, Movement Disorder Soc C1 Univ Washington, Dept Neurol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, NW Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA 98034 USA. Virginia Mason Med Ctr, Dept Neurol, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Portland VA Med Ctr, NW Parkinsons Dis Res Educ & Clin Ctr, Portland, OR USA. Albany Med Ctr, Dept Neurol, Albany, NY USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2007 VL 22 IS 12 MA 28 BP XII EP XII PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 218CD UT WOS:000249992700070 ER PT J AU Tennyson, H Helling, ER Wiseman, J Dick, E Lyons, RC AF Tennyson, Heath Helling, Eric R. Wiseman, Joseph Dick, Edward Lyons, Robert C. TI The effect of topical mitomycin c on full-thickness burns SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID EXPOSURES; SCALE AB Background: Burns result in substantial morbidity because of fibroblast proliferation and contracture. Mitomycin C is a chemotherapeutic agent known to suppress fibroblast proliferation. It is used in ophthalmologic disorders and reduces scarring in upper aerodigestive surgery. No study of the effect of mitomycin C on cutaneous burns has been performed. This study examined burn healing in the presence of topical mitomycin C by evaluation of wound appearance, contraction, and histology in a pig model. Methods: Standardized full-thickness burns were produced on the flanks of three pigs. One animal received no further therapy and was an external control. Two animals under-went placement of topical mitomycin C, 0.4 mg/ml, on selected burn sites for 5 minutes. This was repeated 2 and 4 weeks after injury. Evaluation was performed at 2 and 6 months using a clinical assessment scale and a visual analogue scale. Scar length and histologic analysis were also evaluated. Results: Clinical assessment scale and visual analogue scale scores showed improved appearance in the untreated external control wounds versus the untreated internal control and treated wounds (p < 0.001). Wound contraction was not significantly different between groups. Histologic characteristics between groups were similar except for epidermal hyperplasia, which was decreased in the untreated external control (p < 0.05) at 2 months after treatment. Conclusions: Topical mitomycin C treatment of full-thickness burn wounds at 0.4 mg/cc for three courses does not improve, and may worsen, clinical appearance and scarring during early healing. There is no difference in histology during the long. term healing process. Scar contraction was unchanged. C1 Univ Texas, Hlth Sci Ctr, Plast Surg Serv, San Antonio, TX USA. Ft Sam Houston, Brooke Army Med Ctr, Otolaryngol Serv, San Antonio, TX USA. Landstuhl Reg Med Ctr, Otolaryngol Serv, Landstuhl, Germany. US Army Inst Surg Res, Vet Serv, Ft Sam Houston, San Antonio, TX USA. Audie L Murphy Vet affairs Med Ctr, Plast Surg Serv, San Antonio, TX USA. RP Helling, ER (reprint author), Tripler Army Med Ctr, Plast Surg Serv, 1 Jarrett White Rd, Honolulu, HI 96859 USA. EM eric.helling@us.army.mil NR 13 TC 5 Z9 6 U1 0 U2 1 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 SEP 15 PY 2007 VL 120 IS 4 BP 879 EP 886 DI 10.1097/01.prs.0000277666.07097.55 PG 8 WC Surgery SC Surgery GA 208XK UT WOS:000249352300008 PM 17805114 ER PT J AU Biederman, J Mick, EO Surman, C Doyle, R Hammerness, P Michel, E Martin, J Spencer, TJ AF Biederman, Joseph Mick, Eric O. Surman, Craig Doyle, Robert Hammerness, Paul Michel, Evan Martin, Jessica Spencer, Thomas J. TI Comparative acute efficacy and tolerability of OROS and immediate release formulations of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder SO BMC PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; COMORBIDITY; PREVALENCE; SYMPTOMS; PLACEBO; STATES; TRIAL; ADHD AB Background: The main aim of this study was to compare the safety and efficacy of IR MPH administered three times daily to those of once daily OROS-MPH. Methods: Subjects were outpatient adults satisfying full diagnostic criteria for DSM-IV ADHD between 19 and 60 years of age. Data from two independently conducted 6-week placebo controlled, randomized clinical trials of IR-MPH (tid) and of OROS-MPH were pooled to create three study groups: Placebo (N = 116), IR-MPH (tid) (N = 102) and OROS-MPH (N = 67). Results: Eight-five percent (N = 99) of placebo treated subjects, 77% (N = 79) of the IR-MPH ( tid) treated subjects, and 82% (N = 55) of the OROS-MPH treated subjects completed the 6-week trial. Total daily doses at endpoint were 80.9 +/- 31.9 mg, 74.8 +/- 26.2 mg, and 95.4 +/- 26.3 mg in the OROS-MPH, IR-MPH (tid), and placebo groups, respectively. At endpoint, 66% (N = 44) of subjects receiving OROS-MPH and 70% (N = 71) of subjects receiving IR-MPH (tid) were considered responders compared with 31% ( N = 36) on placebo. Conclusion: Comparison of data from two similarly designed, large, randomized, placebo-controlled, trials, showed that equipotent daily doses of once daily OROS-MPH had similar efficacy to that of TID administered IR MPH. C1 Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Adult ADHD, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. EM jbiederman@partners.org; emick1@partners.org; csurman@partners.org; rdoyle@partners.org; phammerness@partners.org; emichel1@partners.org; jmartin8@partners.org; tspencer@partners.org OI Mick, Eric/0000-0001-8505-8145 FU NIMH NIH HHS [K01 MH065523, KO1 MH065523, R29 MH057511, R29MH57511] NR 23 TC 20 Z9 20 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD SEP 14 PY 2007 VL 7 AR 49 DI 10.1186/1471-244X-7-49 PG 8 WC Psychiatry SC Psychiatry GA 230KV UT WOS:000250876300001 PM 17868455 ER PT J AU Edderkaoui, M Hong, P Lee, JK Pandol, SJ Gukovskaya, AS AF Edderkaoui, Mouad Hong, Peggy Lee, Jong K. Pandol, Stephen J. Gukovskaya, Anna S. TI Insulin-like growth factor-I receptor mediates the prosurvival effect of fibronectin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE-CELLS; EXTRACELLULAR-MATRIX PROTEINS; PANCREATIC-CANCER CELLS; FOCAL ADHESION KINASE; IGF-I; ALPHA-V-BETA-3 INTEGRIN; APOPTOSIS; PHOSPHORYLATION; PROLIFERATION; STATISTICS AB We recently showed that extracellular matrix ( ECM) proteins, which are abundant in desmoplastic pancreatic tumor, are as potent as growth factors in inhibiting apoptosis in pancreatic cancer ( PaCa) cells. Here we show that fibronectin, a major ECM component, engages insulin-like growth factor-I receptor ( IGF-IR) to inhibit PaCa cell death. We found that fibronectin-induced protection from apoptosis is fully mediated by IGF-IR and is independent of IGF-I. Pharmacologic and molecular inhibitions of IGF-IR stimulated apoptosis and prevented the prosurvival effect of fibronectin in PaCa cells. Our data indicate that fibronectin protects from apoptosis through trans-activation of IGF-IR. We showed that fibronectin stimulated complex formation between its receptor beta 3 integrin and protein-tyrosine phosphatase SHP-2. This process of complex formation, in turn, prevents SHP- 2 from dephosphorylating IGF-IR resulting in sustained phosphorylation of IGF-IR and leading to the downstream activation of Akt kinase, up-regulation of antiapoptotic BclxL, and inhibition of apoptosis. Among ECM proteins tested only fibronectin and laminin but not vitronectin and collagen I stimulated trans-activation of IGF-IR. Interaction of fibronectin with beta 3 but not beta 1 integrin receptors mediates the survival pathway. In contrast, fibronectin-induced adhesion is mediated through beta 1 integrin receptor and is IGF-IR-independent. Thus, our results indicate that the prosurvival effect of fibronectin in PaCa cells is mediated by trans-activation of IGF-IR induced by the beta 3 integrin receptor. The data suggest IGF-IR as a key target for prevention of the prosurvival effects of ECM proteins and growth factors in pancreatic cancer. C1 W Los Angeles Vet Affairs Hlth Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90073 USA. Sungkyunkwan Univ, Sch Med, Seoul 135710, South Korea. RP Gukovskaya, AS (reprint author), W Los Angeles Vet Affairs Hlth Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd,Bldg 258,Rm 340, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NCI NIH HHS [R01 CA 119025-01] NR 30 TC 29 Z9 31 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 14 PY 2007 VL 282 IS 37 BP 26646 EP 26655 DI 10.1074/jbc.M702836200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208FJ UT WOS:000249304900003 PM 17627944 ER PT J AU Patel, DN King, CA Bailey, SR Holt, JW Venkatachalam, K Agrawal, A Valente, AJ Chandrasekar, B AF Patel, Devang N. King, Carter A. Bailey, Steven R. Holt, Jeffrey W. Venkatachalam, Kaliyamurthi Agrawal, Alok Valente, Anthony J. Chandrasekar, Bysani TI Interleukin-17 stimulates C-reactive protein expression in hepatocytes and smooth muscle cells via p38 MAPK and ERK1/2-dependent NF-kappa B and C/EBP beta activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CORONARY-HEART-DISEASE; NECROSIS-FACTOR-ALPHA; SERUM AMYLOID-A; CARDIOVASCULAR-DISEASE; NUCLEAR-FACTOR; TNF-ALPHA; ENDOTHELIAL-CELLS; INFLAMMATION; COMPLEMENT; CYTOKINE AB Elevated systemic levels of the acute phase C-reactive protein (CRP) are predictors of future cardiovascular events. There is evidence that CRP may also play a direct role in atherogenesis. Here we determined whether the proinflammatory interleukin (IL)-17 stimulates CRP expression in hepatocytes (Hep3B cell line and primary hepatocytes) and coronary artery smooth muscle cells (CASMC). Our results demonstrate that IL-17 potently induces CRP expression in Hep3B cells independent of IL-1 beta and IL-6. IL-17 induced CRP promoter-driven reporter gene activity that could be attenuated by dominant negative I kappa B alpha or C/EBP beta knockdown and stimulated both NF-kappa B and C/EBP DNA binding and reporter gene activities. Targeting NF-kappa B and C/EBP beta activation by pharmacological inhibitors, small interfering RNA interference and adenoviral transduction of dominant negative expression vectors blocked IL-17-mediated CRP induction. Overexpression of wild type p50, p65, and C/EBP beta stimulated CRP transcription. IL-17 stimulated p38 MAPK and ERK1/2 activation, and SB203580 and PD98059 blunted IL-17-mediated NF-kappa B and C/EBP activation and CRP transcription. These results, confirmed in primary human hepatocytes and CASMC, demonstrate for the first time that IL-17 is a potent inducer of CRP expression via p38 MAPK and ERK1/2-dependent NF-kappa B and C/EBP beta activation and suggest that IL-17 may mediate chronic inflammation, atherosclerosis, and thrombosis. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. E Tennessee State Univ, Dept Pharmacol, Johnson City, TN 37614 USA. S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. RP Chandrasekar, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM chandraseka@uthscsa.edu FU NHLBI NIH HHS [HL 68020, R01 HL068020, R01 HL071233] NR 58 TC 112 Z9 122 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 14 PY 2007 VL 282 IS 37 BP 27229 EP 27238 DI 10.1074/jbc.M703250200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208FJ UT WOS:000249304900064 PM 17652082 ER PT J AU Stuart, LM Bell, SA Stewart, CR Silver, JM Richard, J Goss, JL Tseng, AA Zhang, A El Khoury, JB Moore, KJ AF Stuart, Lynda M. Bell, Susan A. Stewart, Cameron R. Silver, Jessica M. Richard, James Goss, Julie L. Tseng, Anita A. Zhang, Ailiang El Khoury, Joseph B. Moore, Kathryn J. TI CD36 signals to the actin cytoskeleton and regulates microglial migration via a p130Cas complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC-TRANSFORMED CELLS; ALZHEIMERS-DISEASE; TYROSINE PHOSPHORYLATION; PLASMODIUM-FALCIPARUM; SCAVENGER RECEPTOR; PHAGOCYTOSIS; IDENTIFICATION; TRANSDUCTION; MONOCYTES; PROTEINS AB The pattern recognition receptor CD36 initiates a signaling cascade that promotes microglial activation and recruitment to beta-amyloid deposits in the brain. In the present study we identify the focal adhesion-associated proteins p130Cas, Pyk2, and paxillin as novel members of the tyrosine kinase signaling pathway downstream of CD36 and show that assembly of this complex is essential for microglial migration. In primary microglia and macrophages exposed to beta-amyloid, the scaffolding protein p130Cas is rapidly tyrosine-phosphorylated and co-localizes with CD36 to membrane ruffles contemporaneous with F-actin polymerization. These beta-amyloid-stimulated events are not detected in CD36 null cells and are dependent on CD36 activation of Src family tyrosine kinases. Fyn, a Src kinase known to interact with CD36, co-precipitates with p130Cas and is an essential upstream intermediate in the signaling pathways leading to phosphorylation of the p130Cas substrate domain. Furthermore, the p130Cas-interacting kinase Pyk2 and the cytoskeletal adapter protein paxillin also demonstrate CD36-dependent phosphorylation, identifying these focal adhesion molecules as additional members of this beta-amyloid signaling cascade. Disruption of this p130Cas complex by small interfering RNA silencing inhibits p44/42 mitogen-activated protein kinase phosphorylation and microglial migration, illustrating the importance of this pathway in microglial activation and recruitment. Together, these data are the first to identify the signaling cascade that directly links CD36 to the actin cytoskeleton and, thus, implicates it in diverse processes such as cellular migration, adhesion, and phagocytosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02114 USA. Univ Edinburgh, Ctr Inflammat Res, Edinburgh EH16 4TJ, Midlothian, Scotland. RP Moore, KJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, 55 Fruit St,GRJ1308, Boston, MA 02114 USA. EM kmoore@molbio.mgh.harvard.edu RI Stewart, Cameron/E-6823-2011; OI Moore, kathryn/0000-0003-2505-2547 FU NIA NIH HHS [R01 AG 20255]; Wellcome Trust [068089/Z/02/Z] NR 36 TC 46 Z9 46 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 14 PY 2007 VL 282 IS 37 BP 27392 EP 27401 DI 10.1074/jbc.M702887200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208FJ UT WOS:000249304900081 PM 17623670 ER PT J AU Zhong, WM Dixit, SB Mallis, RJ Arthanari, H Lugovskoy, AA Beveridge, DL Wagner, G Reinherz, EL AF Zhong, Weimin Dixit, Surjit B. Mallis, Robert J. Arthanari, Haribabu Lugovskoy, Alexey A. Beveridge, David L. Wagner, Gerhard Reinherz, Ellis L. TI CTL recognition of a protective immunodominant influenza a virus nucleoprotein epitope utilizes a highly restricted V beta but diverse V alpha repertoire: Functional and structural implications SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE influenza A virus; alpha beta T cell receptors; immune recognition; molecular modeling; molecular dynamics ID CELL ANTIGEN RECEPTOR; PARTICLE MESH EWALD; IMMUNE-RESPONSE; SELECTION; PEPTIDE; ESCAPE; SYSTEM; PREDICTION; MOLECULES; VARIANTS AB To investigate protective immunity conferred by CTL against viral pathogens, we have analyzed CD8(+) T cell responses to the immunodominant nucleoprotein epitope (NP366-374) of influenza A virus in 136 mice during primary and secondary infections in vivo. Unlike the highly biased TCRV beta repertoire, the associated V alpha repertoire specific for the NP366-374/D-b ligand is quite diverse. Nonetheless, certain public and conserved CDR3 alpha clonotypes with distinct molecular signatures were identified. Pairing of public V alpha and V beta domains creates an at TCR heterodimer that binds efficiently to the NP366-374/D-b ligand and stimulates T cell activation. In contrast, private TCRs, each comprising a distinct a chain paired with the same public [ chain, interact very differently. Molecular dynamics simulation reveals that the conformation and mobility of the shared V beta CDR loops are governed largely by the associated Va domains. These results provide insight into molecular principles regarding public versus private TCRs linked to immune surveillance after infection with influenza A virus. (C) 2007 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Immunobiol Lab, Boston, MA 02115 USA. Wesleyan Univ, Dept Chem, Mol Biophys Program, Hall Atwater Labs, Middletown, CT 06459 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Biogen Inc, Mol Modeling, Cambridge, MA 02142 USA. RP Zhong, WM (reprint author), Ctr Dis Control & Prevention, Natl Ctr Infect Dis, Influenza Div, Mailsop G-16,1600 Clifton Rd, Atlanta, GA 30333 USA. EM wzhong@cdc.gov; ellis-reinherz@dfci.harvard.edu RI Mallis, Robert/A-2270-2015 FU NIAID NIH HHS [U19 AI57330, AI19807, AI37581] NR 37 TC 22 Z9 23 U1 0 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 14 PY 2007 VL 372 IS 2 BP 535 EP 548 DI 10.1016/j.jmb.2007.06.057 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 209EQ UT WOS:000249372200021 PM 17658550 ER PT J AU Getz, G Hofling, H Mesirov, JP Golub, TR Meyerson, M Tibshirani, R Lander, ES AF Getz, Gad Hoefling, Holger Mesirov, Jill P. Golub, Todd R. Meyerson, Matthew Tibshirani, Robert Lander, Eric S. TI Comment on "The consensus coding sequences of human breast and colorectal cancers" SO SCIENCE LA English DT Editorial Material C1 MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Cambridge, MA 02142 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Getz, G (reprint author), MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02142 USA. EM gadgetz@broad.mit.edu RI Meyerson, Matthew/E-7123-2012 NR 4 TC 10 Z9 10 U1 0 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 14 PY 2007 VL 317 IS 5844 DI 10.1126/science.1138764 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 210PK UT WOS:000249467900020 ER PT J AU Januzzi, JL Garasic, JM Neilan, TG Gonzalez, RG Stone, JR AF Januzzi, James L., Jr. Garasic, Joseph M. Neilan, Tomas G. Gonzalez, R. Gilberto Stone, James R. TI Case 28-2007: A 68-year-old man with syncope SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC MYXOMA; THROMBUS C1 Massachusetts Gen Hosp, Coronary Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vasc Med Sect, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Coronary Care Unit, Boston, MA 02114 USA. NR 17 TC 3 Z9 3 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 13 PY 2007 VL 357 IS 11 BP 1137 EP 1145 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 209KK UT WOS:000249387200011 PM 17855675 ER PT J AU Rasmussen, RA Ong, H Song, R Chenine, AL Ayash-Rashkovsky, M Hu, SL Polacino, P Else, JG Novembre, FJ Ruprecht, RA AF Rasmussen, Robert A. Ong, Helena Song, Ruijiang Chenine, Agnes-Laurence Ayash-Rashkovsky, Mila Hu, Shiu-Lok Polacino, Patricia Else, James G. Novembre, Francis J. Ruprecht, Ruth A. CA Clade C Program Project TI Efficacy of a multigenic protein vaccine containing multimeric HIV gp160 against heterologous SHIV clade C challenges SO AIDS LA English DT Article DE animal model; HIV clade C; multimeric gp160; protein immunization; SHIV; vaccine ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODIES; CORE ANTIGENS; ENVELOPE; TYPE-1; MACAQUES; IMMUNOGENICITY; INFECTION; IMMUNIZATION; EXPRESSION AB Objective: To determine whether multigenic protein immunogens including native, trimeric HIV clade C (HIV-C) gp160 could cross-protect macaques against mucosal challenge with clade C (SHIV-C) mismatched for env. Design: Because AIDS vaccine recipients are unlikely to encounter exactly matched HIV strains and to represent the diversity of locally circulating HIV-C strains, we selected env genes to generate the gp160 immunogen and SHIV-C from different, recently infected infants of the same clinical cohort in Zambia. in a model of postnatal HIV-C transmission, infant macaques were immunized with soluble viral proteins, including trimeric HIV1084i Env, and challenged with SHIV-1157ip; protein-only vaccination was compared with a DNA prime/protein boost strategy. Methods: All vaccinated and control monkeys were exposed orally to low-dose, R5-tropic SHIV-1157ip encoding heterologous env. Animals with no or only transient infection were rechallenged intrarectally with a high dose of R5 SHIV-1157ipd3N4, a 'late', animal-evolved SHIV-1157ip variant. Animals were followed prospectively for immune parameters and viral RNA loads. Results: Vaccination induced cross-neutralizing antibodies. Compared to controls, vaccinees had significantly lower peak viral RNA loads, and one vaccine recipient remained completely virus-free, even in lymphoid tissues. There was a trend for the protein-only vaccine to yield better protection than the combined modality approach. Conclusion: Protein-only immunogens induced significant protection against heterologous viruses encoding env from locally circulating viruses. (C) 2007 Lippincott Williams & Wilkins. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Washington, Seattle, WA 98195 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RP Rasmussen, RA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NCRR NIH HHS [RR00165]; NIAID NIH HHS [P01 AI48240] NR 25 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD SEP 12 PY 2007 VL 21 IS 14 BP 1841 EP 1848 DI 10.1097/QAD.0b013e32828684ea PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 213DA UT WOS:000249645000003 PM 17721091 ER PT J AU Schifitto, G Navia, BA Yiannoutsos, CT Marra, CM Chang, L Ernst, T Jarvik, JG Miller, EN Singerg, EJ Ellis, RJ Kolson, DL Simpson, D Nath, A Berger, J Shriver, SL Millar, LL Colquhoun, D Lenkinski, R Gonzalez, RG Liptonq, SA AF Schifitto, Giovanni Navia, Bradford A. Yiannoutsos, Constantin T. Marra, Christina M. Chang, Linda Ernst, Thomas Jarvik, Jeffrey G. Miller, Eric N. Singerg, Elyse J. Ellis, Ronald J. Kolson, Dennis L. Simpson, David Nath, Avindra Berger, Joseph Shriver, Sharon L. Millar, Linda L. Colquhoun, Dodi Lenkinski, Robert Gonzalez, R. Gilberto Liptonq, Stuart A. CA Adult AIDS Clin Trial Grp HIV MRS Consortium TI Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study SO AIDS LA English DT Article DE HIV dementia; dementia; neuroprotection; neuroimaging; AIDS; HIV; memantine ID AIDS DEMENTIA COMPLEX; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS-INFECTION; NMDA RECEPTOR ANTAGONIST; CONTROLLED-TRIAL; SEROPOSITIVE INDIVIDUALS; METABOLITE ABNORMALITIES; COMBINATION THERAPY; DISEASE; ERA AB Objective: To assess the safety and efficacy of memantine, an uncompetitive antagonist of the N-methyl-D-aspartate receptor as treatment of HIV-associated cognitive impairment. Methods: This was a Phase 11 randomized, double-blind, placebo-controlled, multicenter trial within the Adult AIDS Clinical Trials Group. One-hundred and forty HIV-infected adults with mild to severe AIDS dementia complex receiving stable antiretroviral therapy were enrolled. Memantine was initiated at 10 mg daily escalated to 40 mg daily, or up to the maximum tolerated dose and continued for 16 weeks (primary evaluation visit) followed by a 4-week washout period and re-evaluation at week 20. Changes in cognitive performance were measured as percent change from baseline to week 16 in the average of eight neuropsychological test scores (NPZ-8). Brain metabolism was measured by magnetic resonance spectroscopy in a subgroup of subjects. Results: Sixty-one percent of subjects in the memantine group and 85% in the placebo group reached the 40 mg dose while the reported adverse experiences between the two groups were similar. There were no significant improvements in neuropsychological performance over 16 weeks; however, memantine was associated with a significant increase at week 16 in the N-acetyl aspartate to creatine ratio, in the frontal white matter (P=0.040) and parietal cortex (P=0.023). Conclusions: Memantine was safe and tolerated by HIV-infected subjects with cognitive impairment. Although we observed no significant differences in cognitive performance, the magnetic resonance spectroscopy data suggest that memantine may ameliorate neuronal metabolism, an important step to stabilizing or preventing neuronal injury. These results underscore the need for longer studies to assess the full potential of neuroprotective agents. (C) 2007 Lippincott Williams & Wilkins. C1 Univ Rochester, Rochester, NY USA. Tufts Univ, Sch Med, Dept Neurol & Psychiat, Infect Unit, Boston, MA 02111 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ Washington, Seattle, WA 98195 USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. Univ Calif Los Angeles, Ctr Med, Los Angeles, CA 90024 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Penn, Philadelphia, PA 19104 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Johns Hopkins Med Ctr, Baltimore, MD USA. Univ Kentucky, Med Ctr, Lexington, KY USA. AACTG Operat Off, Rockville, MD USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Univ Calif San Diego, Burnham Inst Med Res, San Diego, CA 92103 USA. Salk Inst Biol Studies, Scripps Res Inst, La Jolla, CA 92037 USA. RP Schifitto, G (reprint author), Univ Rochester, Dept Neurol, 1351 Mt Hope Ave,Suite 223, Rochester, NY 14620 USA. EM giovanni.schifitto@ctcc.rochester.edu RI Lenkinski, Robert/F-9045-2014; Ellis, Ronald/K-3543-2015; OI Ellis, Ronald/0000-0003-4931-752X; Lenkinski, Robert/0000-0001-7371-5048 FU NCRR NIH HHS [R01RR13213, 5M01 RR00044]; NIAID NIH HHS [AI38855, AI38858]; NINDS NIH HHS [R01NS34626, R01NS38834] NR 50 TC 69 Z9 72 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD SEP 12 PY 2007 VL 21 IS 14 BP 1877 EP 1886 DI 10.1097/QAD.0b013e32813384e8 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 213DA UT WOS:000249645000007 PM 17721095 ER PT J AU Jamison, RL Hartigan, P Kaufman, JS Goldfarb, DS Warren, SR Guarino, PD Gaziano, JM AF Jamison, Rex L. Hartigan, Pamela Kaufman, James S. Goldfarb, David S. Warren, Stuart R. Guarino, Peter D. Gaziano, J. Michael CA Veterans Affairs Site Invest TI Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; FOLIC-ACID SUPPLEMENTATION; CARDIOVASCULAR EVENTS; VITAMIN INTERVENTION; PLASMA HOMOCYSTEINE; DIALYSIS PATIENTS; HEART-DISEASE; RISK-FACTORS; HYPERHOMOCYSTEINEMIA; ATHEROSCLEROSIS AB Context High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown. Objective To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease. Design, Setting, and Participants Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance <= 30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (>= 15 mu mol/L). Intervention Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B-6), and 2 mg of cyanocobalamin (vitamin B-12) or a placebo. Main Outcome Measures The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients. Results Mean baseline homocysteine level was 24.0 mu mol/L in the vitamin group and 24.2 mu mol/L in the placebo group. It was lowered 6.3 mu mol/L (25.8%; P < .001) in the vitamin group and 0.4 mu mol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality ( 448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups. Conclusion Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease. C1 Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Div Nephrol, Dept Med, Stanford, CA 94305 USA. VA Connecticut Healthcare Syst, VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. VA Boston Healthcare Syst, Renal Sect, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. New York Harbor Healthcare Syst, Nephrol Sect, New York, NY USA. NYU, Sch Med, New York, NY USA. Clin Res Pharm Coordinating Ctr, VA Cooperat Studies Program, Albuquerque, NM USA. Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat MAVERI, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. RP Jamison, RL (reprint author), Vet Affairs Palo Alto Hlth Care Syst, MB3 Room 305,M-C HOST 151,3801 Miranda Ave, Palo Alto, CA 94304 USA. EM rjamison@stanford.edu NR 37 TC 257 Z9 267 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 12 PY 2007 VL 298 IS 10 BP 1163 EP 1170 DI 10.1001/jama.298.10.1163 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 209FK UT WOS:000249374200021 PM 17848650 ER PT J AU Wang, TJ AF Wang, Thomas J. TI Significance of circulating troponins in heart failure - If these walls could talk SO CIRCULATION LA English DT Editorial Material DE editorials; biomarkers; heart failure; troponin ID FAILING HUMAN HEART; CARDIAC TROPONIN; NATRIURETIC PEPTIDE; DILATED CARDIOMYOPATHY; MYOCARDIAL INJURY; PROGNOSTIC VALUE; MYOCYTE DEATH; CELL-DEATH; DYSFUNCTION; PREDICTION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org NR 29 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 11 PY 2007 VL 116 IS 11 BP 1217 EP 1220 DI 10.1161/CIRCULATIONAHA.107.721845 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 208QL UT WOS:000249334200002 PM 17846340 ER PT J AU Pou, KM Massaro, JM Hoffmann, U Vasan, RS Maurovich-Horvat, P Larson, MG Keaney, JF Meigs, JB Lipinska, I Kathiresan, S Murabito, JM O'Donnell, CJ Benjamin, EJ Fox, CS AF Pou, Karla M. Massaro, Joseph M. Hoffmann, Udo Vasan, Ramachandran S. Maurovich-Horvat, Pal Larson, Martin G. Keaney, John F., Jr. Meigs, James B. Lipinska, Izabella Kathiresan, Sekar Murabito, Joanne M. O'Donnell, Christopher J. Benjamin, Emelia J. Fox, Caroline S. TI Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress - The framingham heart study SO CIRCULATION LA English DT Article DE obesity; abdominal visceral fat; inflammation; computed tomography; epidemiology ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INSULIN-RESISTANCE; METABOLIC SYNDROME; FACTOR-ALPHA; BODY-FAT; RISK-FACTORS; OBESE WOMEN; WEIGHT-LOSS AB Background-Excess adiposity is associated with greater systemic inflammation. Whether visceral adiposity is more proinflammatory than subcutaneous abdominal adiposity is unclear. Methods and Results-We examined the relations of abdominal subcutaneous adipose tissue ( SAT) and visceral adipose tissue ( VAT), assessed by multidetector computerized tomography, to circulating inflammatory and oxidative stress biomarkers in 1250 Framingham Heart Study participants (52% women; age 60 +/- 9 years). Biomarkers were examined in relation to increments of SAT and VAT after adjustment for age, sex, smoking, physical activity, menopause, hormone replacement therapy, alcohol, and aspirin use; additional models included body mass index and waist circumference. SAT and VAT were positively and similarly ( with respect to strength of association) related to C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, P-selectin, and tumor necrosis factor receptor-2 (multivariable model R-2 0.06 to 0.28 [ SAT] and 0.07 to 0.29 [ VAT]). However, compared with SAT, VAT was more highly associated with urinary isoprostanes and monocyte chemoattractant protein-1 ( SAT versus VAT comparison: isoprostanes, R2 0.07 versus 0.10, P = 0.002; monocyte chemoattractant protein-1, R2 0.07 versus 0.08, P = 0.04). When body mass index and waist circumference were added to the models, VAT remained significantly associated with only C-reactive protein ( P = 0.0003 for women; P = 0.006 for men), interleukin-6 ( P = 0.01), isoprostanes ( P = 0.0002), and monocyte chemoattractant protein-1 ( P = 0.008); SAT only remained associated with fibrinogen ( P = 0.01). Conclusions-The present cross-sectional data support an association between both SAT and VAT with inflammation and oxidative stress. The data suggest that the contribution of visceral fat to inflammation may not be completely accounted for by clinical measures of obesity ( body mass index and waist circumference). C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Brigham & Womens Hosp, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA 02115 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Dept Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Dept Prevent Med, Boston, MA 02118 USA. Semmelweis Univ, H-1085 Budapest, Hungary. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Murabito, Joanne/0000-0002-0192-7516; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Maurovich-Horvat, Pal/0000-0003-0885-736X FU NHLBI NIH HHS [R01-HL076784, 2K24HL04334, N01-HC-25195, R01-HL064753]; NIA NIH HHS [R01-AG028321]; NIDDK NIH HHS [T32 DK007529] NR 52 TC 409 Z9 419 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 11 PY 2007 VL 116 IS 11 BP 1234 EP 1241 DI 10.1161/CIRCULATIONAHA.107.710509 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 208QL UT WOS:000249334200006 PM 17709633 ER PT J AU Raher, MJ Thibault, H Poh, KK Liu, R Halpern, EF Derumeaux, G Ichinose, F Zapol, WM Bloch, KD Picard, MH Scherrer-Crosbie, M AF Raher, Michael J. Thibault, Helene Poh, Kian Keong Liu, Rong Halpern, Elkan F. Derumeaux, Genevieve Ichinose, Fumito Zapol, Warren M. Bloch, Kenneth D. Picard, Michael H. Scherrer-Crosbie, Marielle TI In vivo characterization of murine myocardial perfusion with myocardial contrast echocardiography - Validation and application in nitric oxide synthase 3-deficient mice SO CIRCULATION LA English DT Article DE nitric oxide synthase; adenosine; acetylcholine; microspheres ID CORONARY BLOOD-FLOW; REAL-TIME; DEFICIENT MICE; KNOCKOUT MICE; RESERVE; QUANTIFICATION; ULTRASOUND; ADENOSINE; HUMANS; STENOSIS AB Background-The ability to noninvasively evaluate murine myocardial blood flow (MBF) in vivo would provide an important tool for cardiovascular research. Myocardial contrast echocardiography (MCE) has been used to measure MBF; however, it has not been validated in mice. This study assesses whether MCE can evaluate MBF at rest and after vasodilation and measure the maximal augmentation ( coronary reserve) of MBF in mice. Wild-type (WT) and nitric oxide synthase 3 (NOS3)-deficient (NOS3(-/-) ) mice were studied. Methods and Results-MCE was performed at baseline and after intravenous infusion of acetylcholine or adenosine. Definity contrast agent was infused, and parasternal views were acquired in real-time mode. Replenishment curves of myocardial contrast were obtained, and rates of signal rise (beta) and plateau intensity ( A) were calculated. MBF estimated by the product of A and beta ( A beta) was compared with that measured with fluorescent microspheres. MCE analysis was feasible in 98% ( 52/53) of mice. MBF measured by microspheres increased with adenosine and correlated closely with A beta. There was no difference in MCE-derived MBF between WT and NOS3 (-/-) mice at rest. Adenosine infusion increased MBF by 3.0 +/- 0.6-fold in NOS3 (-/-) mice and 2.5 +/- 0.3-fold in WT ( P = 0.58 between genotypes). Acetylcholine induced an increase of 2.4 +/- 0.2-fold in MBF in WT mice but did not increase MBF in NOS3 (-/-) mice ( P < 0.0005 versus WT). Conclusions-MBF, coronary reserve, and vasodilator responses can be evaluated accurately in the intact mouse by MCE. This method demonstrated a preserved coronary response to adenosine but an impaired acetylcholine-induced vasodilation in NOS3 (-/-) mice compared with WT mice. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Lyon 1, INSERM E 0226, F-69365 Lyon, France. 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 OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL-42397, HL-71987, HL-70896]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-12] NR 45 TC 25 Z9 25 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 11 PY 2007 VL 116 IS 11 BP 1250 EP 1257 DI 10.1161/CIRCULATIONAHA.107.707737 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 208QL UT WOS:000249334200008 PM 17709634 ER PT J AU Beeri, R Yosefy, C Guerrero, JL Abedat, S Handschumacher, MD Stroud, RE Sullivan, S Chaput, M Gilon, D Vlahakes, GJ Spinale, FG Hajjar, RJ Levine, RA AF Beeri, Ronen Yosefy, Chaim Guerrero, J. Luis Abedat, Suzan Handschumacher, Mark D. Stroud, Robert E. Sullivan, Suzanne Chaput, Miguel Gilon, Dan Vlahakes, Gus J. Spinale, Francis G. Hajjar, Roger J. Levine, Robert A. TI Early repair of moderate ischemic mitral regurgitation reverses left ventricular remodeling SO CIRCULATION LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc DE mitral valve; myocardial infarction; regurgitation; remodeling; surgery ID MATRIX-METALLOPROTEINASE ACTIVITY; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; 3-DIMENSIONAL ECHOCARDIOGRAPHY; CLINICAL-IMPLICATIONS; MYOCYTE FUNCTION; VOLUME OVERLOAD; IN-VIVO; HYPERTROPHY; DYSFUNCTION AB Background - Mitral regurgitation (MR) doubles postmyocardial infarction (MI) mortality. We have shown that moderate MR augments remodeling in an apical MI model ( no intrinsic MR) with independent left ventricle-to-left atrial MR-type flow. We hypothesized that repairing moderate MR 1 month after MI reverses this remodeling. Methods and Results - Anteroapical MIs were created in 18 sheep, and a left ventricle-to-left atrial shunt implanted in 12 (regurgitant fraction, 30%). Six sheep had the shunt closed at 1 month ( repair group). Sheep were compared at baseline, and at 1 and 3 months. Sheep in the MI + MR (unrepaired) and repaired groups remodeled during the first month (120% increased left ventricular end-systolic volume [ESV; P < 0.01]), but shunt closure reversed remodeling at 3 months, with end-diastolic volume (EDV) and ESV 135% and 128% of baseline versus 220% and 280% without repair (P < 0.001). At 3 months, dP/dt and preload-recruitable stroke work were relatively maintained in the repaired and MI-only groups versus nearly 50% decreases without repair. Prohypertrophic gp130 and antiapoptotic pAkt increased followed by exhaustion below baseline without repair, but remained elevated at 3 months with repair or MI only. With repair, matrix metalloproteinase-2 decreased to <= 50% that without repair in remote and border zones at 3 months, and the matrix metalloproteinase inhibitor TIMP-4 increased dramatically. Conclusions - Early repair of moderate MR in the setting of apical MI substantially reverses the otherwise progressive remodeling process, with reduced left ventricular volumes, relatively maintained contractility, persistently activated intracellular signals promoting hypertrophy and opposing apoptosis, and reduced matrix proteolytic activity. These findings are of interest for the current controversy regarding potential benefits of repair of MR after MI. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Dept Cardiothorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. Hadassah Hebrew Univ Med Ctr, Inst Heart, Jerusalem, Israel. Med Univ S Carolina, Dept Cardiothorac Surg, Charleston, SC 29425 USA. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Cardiovasc Res Ctr, YAW5,55 Fruit St, Boston, MA 02114 USA. EM rlevine@partners.org RI Beeri, Ronen/A-4035-2009 OI Beeri, Ronen/0000-0002-8014-0702 FU NHLBI NIH HHS [R01HL72265] NR 49 TC 13 Z9 13 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 11 PY 2007 VL 116 IS 11 SU S BP I288 EP I293 DI 10.1161/CIRCULATIONAHA.106.681114 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 209BY UT WOS:000249364500043 PM 17846319 ER PT J AU Collard, CD Shernan, SK Fox, AA Bernig, T Chanock, SJ Vaughn, WK Takahashi, K Ezekowitz, AB Jarolim, P Body, SC AF Collard, Charles D. Shernan, Stanton K. Fox, Amanda A. Bernig, Toralf Chanock, Stephen J. Vaughn, William K. Takahashi, Kazue Ezekowitz, Alan B. Jarolim, Petr Body, Simon C. TI The MBL2 'LYQA secretor' haplotype is an independent predictor of postoperative myocardial infarction in whites undergoing coronary artery bypass graft surgery SO CIRCULATION LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc DE genetics; myocardial infarction; immunology; inflammation; surgery ID MANNOSE-BINDING LECTIN; COMPLEMENT ACTIVATION; GENETIC-VARIATION; OXIDATIVE STRESS; EARLY RESTENOSIS; PROTEIN GENE; PATHWAY; GENOTYPE; RISK; ENDARTERECTOMY AB Background - Mannose-binding lectin (MBL) is an important component of innate immunity and activator of the lectin complement pathway. Within the MBL2 gene are seven 5' "secretor" haplotypes that code for altered serum MBL levels and complement activation. However, recent evidence suggests that 3' MBL2 haplotypes may also modify MBL function and circulating levels. Because MBL and the lectin complement pathway have been implicated in cardiovascular injury, we investigated whether MBL2 haplotypes are independently associated with an increased risk of postoperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft surgery. Methods and Results - Genotyping of 18 polymorphic sites within the MBL2 gene was performed in a prospective, longitudinal multi-institutional study of 978 patients undergoing primary coronary artery bypass graft-only surgery with cardiopulmonary bypass between August 2001 and May 2005. After adjustment for multiple comparisons by permutation testing, multivariate, stepwise logistic regression, including a score test, was performed controlling for patient demographics, preoperative risk factors, medications, and intraoperative variables to determine if MBL2 secretor haplotypes are independent predictors of PMI in whites undergoing primary coronary artery bypass graft surgery. Neither the 5' nor 3' MBL2 haplotypes alone were associated with an increased incidence of PMI. However, the incidence of PMI in whites (n = 843) expressing the combined MBL2 5' LYQA secretor haplotype (CGTCGG) and 3' haplotype (CGGGT) was significantly higher than in whites not expressing the haplotype (38% versus 10%; P < 0.007). Moreover, the combined MBL2 LYQA secretor haplotype was an independent predictor of PMI in whites after primary coronary artery bypass graft surgery after adjustment for other covariates (P < 0.02; adjusted OR: 3.97; 95% CI: 1.30 to 12.07). The combined MBL2 LYQA secretor haplotype in whites was also an independent predictor of postoperative CKMB levels exceeding 60 ng/mL (P < 0.02; adjusted OR: 4.48; 95% CI: 1.95 to 16.80). Inclusion of the combined MBL2 LYQA secretor haplotype improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.715 versus 0.705). Conclusions - The combined MBL2 LYQA secretor haplotype is a novel independent predictor of PMI and may aid in preoperative risk stratification of whites undergoing primary coronary artery bypass graft surgery. C1 St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiovasc Anesthesiol, Houston, TX 77030 USA. Harvard Univ, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Div Biostat & Epidemiol, Houston, TX 77030 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, Boston, MA USA. Merck Res Labs, Rahway, NJ USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. RP Collard, CD (reprint author), St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiovasc Anesthesiol, 6720 Bertner Ave, Houston, TX 77030 USA. EM ccollard@heart.thi.tmc.edu FU NHLBI NIH HHS [K23 HL068774, HL-068774, K23 HL068774-01A1]; PHS HHS [M01 02558] NR 33 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 11 PY 2007 VL 116 IS 11 SU S BP I106 EP I112 DI 10.1161/CIRCULATIONAHA.106.679530 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 209BY UT WOS:000249364500015 PM 17846289 ER PT J AU Hung, J Chaput, M Guerrero, JL Handschumacher, MD Papakostas, L Sullivan, S Solis, J Levine, RA AF Hung, Judy Chaput, Miguel Guerrero, J. Luis Handschumacher, Mark D. Papakostas, Lampros Sullivan, Suzanne Solis, Jorge Levine, Robert A. TI Persistent reduction of ischemic mitral regurgitation by papillary muscle repositioning - Structural stabilization of the papillary muscle-ventricular wall complex SO CIRCULATION LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc DE mitral regurgitation; left ventricular remodeling ID ACUTE MYOCARDIAL-INFARCTION; HEART; ANNULOPLASTY; DYSFUNCTION; MECHANISM; GEOMETRY; ECHOCARDIOGRAPHY; REPAIR; VOLUME AB Background - Recurrent ischemic mitral regurgitation (IMR) is frequent despite initial reduction by annuloplasty because continued LV remodeling increases tethering to the infarcted papillary muscle (PM). We have previously shown that PM repositioning by an external patch device can acutely reduce IMR. In this study, we tested the hypothesis that IMR reduction persists despite possible continued LV remodeling. Methods and Results - In 7 sheep, we used a chronic ischemic posterior infarct model that produces LV dilatation and MR over 10 weeks. An epicardial patch device was adjusted under echo guidance to reduce MR, with follow- up over a further 8 weeks and evaluation by 3D echo and sonomicrometry. In all 7 sheep, moderate IMR resolved with acute patch application and PM repositioning (6.5 +/- 1.8 mm to 0.6 +/- 1.3 mm proximal jet width, P < 0.001) without decrease in LVEF (43 +/- 3% to 44 +/- 8%). Eight weeks after PM repositioning, MR was not significantly greater (0.6 +/- 1.3 mm versus (1.0 +/- 1.0 mm, P = NS) despite an increase in LV volumes in 3 animals (2 had increases of 50 +/- 15%). On average, LV volumes did not change significantly (ESV: 46 +/- 8 mL versus 49 +/- 15 mL; P = NS and EDV: 85 +/- 16 mL versus 89 +/- 30 mL; P = NS). LVEF was unchanged from acute to chronic patch (44 +/- 8% versus 43 +/- 8%). Contractility as end-systolic elastance did not decrease from the chronic MI to the acute and chronic patch stages, nor were there any significant changes in dP/dt, LV stiffness constant, or time constant of LV relaxation (Tau). Conclusion - PM repositioning is persistently effective in reducing moderate chronic IMR, even when LV volume increases. This may reflect structural stabilization by an external patch device of the papillary muscle-LV wall complex that controls mitral valve tethering. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiothorac Surg, Boston, MA 02114 USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 256,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org FU NIBIB NIH HHS [R21 EB005294]; PHS HHS [NHLBI R01 038176] NR 31 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 11 PY 2007 VL 116 IS 11 SU S BP I259 EP I263 DI 10.1161/CIRCULATIONAHA.106.679951 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 209BY UT WOS:000249364500038 PM 17846314 ER PT J AU Tauaj, JA Kirklin, JK Brown, RN Rayburn, BK Bourge, RC Benza, RL Pinderski, L Pamboukian, S McGiffin, DC Naftel, DC AF Tauaj, Jose A. Kirklin, James K. Brown, Robert N. Rayburn, Barry K. Bourge, Robert C. Benza, Raymond L. Pinderski, Laura Pamboukian, Salpy McGiffin, David C. Naftel, David C. TI Post-heart transplant diastolic dysfunction is a risk factor for mortality SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VENTRICULAR EJECTION FRACTION; CARDIAC TRANSPLANTATION; EXERCISE CAPACITY; FAILURE; PHYSIOLOGY; SURVIVAL AB Objectives The purpose of this study was to evaluate the incidence and prognostic implication of diastolic dysfunction (DD) occurring in the first year after transplant. Background Diastolic dysfunction is a recognized complication in heart transplant recipients, but its true incidence and natural history has been poorly characterized. We studied the prognostic implication of DD, as defined by elevated filling pressures with normal systolic function, occurring in the first year after transplant. Methods Between June 1992 and June 2002, all patients who underwent heart transplantation at a single institution were included in the study (231 at 6 weeks and 250 at 6 months and 1 year). Diastolic dysfunction was defined as right atrial pressure (RAP) :15 mm Hg (right ventricular [RV] DD) or pulmonary capillary wedge pressure >= 18 mm Hg (left ventricular [LV] DD) with normal systolic function by echocardiogram and without severe mitral or tricuspid insufficiency. In addition, RV DD was defined by a RAP/stroke volume (SV) ratio. Results The incidence of DID was 22%, 8%, and 12% at 6 weeks, 6 months, and I year, respectively. The incidence of LV DD was more frequent than that of RV DD at any time point (p < 0.0001). By multivariable analysis RV DD, as manifested by an elevated RAP/SV, but not LV DD was a strong predictor of cardiac mortality at all time points. Conclusions Diastolic dysfunction is common early after transplant, and its incidence decreases during the first year. Right ventricular DD, as measured by an elevated RAP/SV ratio, but not LV DD is a strong predictor of cardiac mortality. Further studies are needed to evaluate the functional status of patients with RV or LV DD and whether aggressive medical therapy for early DD could alter outcome. C1 Univ Alabama, THT 338, Dept Cardiovasc Dis, Birmingham, AL 35294 USA. Univ Alabama, Dept Cardiovasc Surg, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. RP Tauaj, JA (reprint author), Univ Alabama, THT 338, Dept Cardiovasc Dis, 1900 Univ Blvd, Birmingham, AL 35294 USA. EM jtallaj@uab.edu NR 15 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 11 PY 2007 VL 50 IS 11 BP 1064 EP 1069 DI 10.1016/j.jacc.2007.06.007 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 208VU UT WOS:000249348100009 ER PT J AU Tsai, CH Chen, JY Szostak, JW AF Tsai, Ching-Hsuan Chen, Jingyang Szostak, Jack W. TI Enzymatic synthesis of DNA on glycerol nucleic acid templates without stable duplex formation between product and template SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE information transfer; polymerase ID IN-VITRO SELECTION; POLYMERASE-I; CHEMICAL ETIOLOGY; LARGE FRAGMENT; TNA SYNTHESIS; CRYSTAL; OLIGONUCLEOTIDES; REPLICATION; SYSTEMS AB Glycerol nucleic acid (GNA) is an interesting alternative base-pairing system based on an acyclic, glycerol-phosphate backbone repeat unit. The question of whether DNA polymerases can catalyze efficient template-dependent synthesis using GNA as the template is of particular interest because GNA is unable to form a stable duplex with DNA. In the present study, we screened a variety of DNA polymerases for GNA-dependent DNA synthesis. We find that Bst DNA polymerase can catalyze full-length DNA synthesis on a dodecamer GNA template. The efficiency of DNA synthesis is increased by replacing adenine with diaminopurine in both the GNA template and the DNA monomers and by the presence of manganese ions. We suggest that the BstDNA polymerase maintains a short, transient region of base-pairing between the DNA product strand and the GNA template, but that stable duplex formation between product and template strands is not required for template-dependent polymerization. C1 Massachusetts Gen Hosp, Ctr Comp & Integrat Biol, Howard Hughes Med Inst, Dept Biol Mol, Boston, MA 02144 USA. Massachusetts Gen Hosp, Simches Res Ctr, Boston, MA 02144 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Ctr Comp & Integrat Biol, Howard Hughes Med Inst, Dept Biol Mol, 185 Cambridge St, Boston, MA 02144 USA. EM szostak@molbio.mgh.harvard.edu NR 29 TC 39 Z9 39 U1 1 U2 10 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 11 PY 2007 VL 104 IS 37 BP 14598 EP 14603 DI 10.1073/pnas.0704211104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 211GT UT WOS:000249513000012 PM 17785419 ER PT J AU Bonasio, R Carman, CV Kim, E Sage, PT Love, KR Mempel, TR Springer, TA von Andrian, UH AF Bonasio, Roberto Carman, Christopher V. Kim, Enoch Sage, Peter T. Love, Kerry R. Mempel, Thorsten R. Springer, Timothy A. von Andrian, Ulrich H. TI Specific and covalent labeling of a membrane protein with organic fluorochromes and quantum dots SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE imaging; integrin; eukocyte adhesion; protein engineering ID MOLECULES IN-VIVO; FUSION PROTEINS; FLUORESCENT PROTEIN; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; INTEGRIN ALPHA-V-BETA-3; EXTRACELLULAR SEGMENT; CRYSTAL-STRUCTURE; LIVING CELLS; DOMAIN; LFA-1 AB The real-time observation of protein dynamics in living cells and organisms is of fundamental importance for understanding biological processes. Most approaches to labeling proteins exploit noncovalent interactions, unsuitable to long-term studies, or genetic fusion to naturally occurring fluorescent proteins that often have unsatisfactory optical properties. Here we used the fungal enzyme cutinase and its suicide substrate p-nitrophenyl phosphonate to covalently attach a variety of labels to the integrin lymphocyte function-associated antigen-1 (LFA-1) on the surface of living cells. Cutinase was embedded in the extracellular domain of LFA-1 with no appreciable influence on integrin function and conformational regulation. p-nitrophenyl phosphonate-conjugated fluorochromes, including the very bright and stable quantum dots, bound efficiently and specifically to LFA-1/cutinase. The availability of a genetically encoded tag that binds covalently to quantum dots could foster the development of new experimental strategies for the study of protein dynamics in Vivo. C1 CBR Inst Biomed Res Inc, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. Surface Logix Inc, Brighton, MA 02135 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP von Andrian, UH (reprint author), CBR Inst Biomed Res Inc, Dept Pathol, Boston, MA 02215 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008; Bonasio, Roberto/P-1356-2014; Carman, Christopher/L-8108-2016 OI Bonasio, Roberto/0000-0002-0767-0889; Carman, Christopher/0000-0001-7358-2548 FU NIAID NIH HHS [AI063854, F32 AI063854] NR 32 TC 55 Z9 55 U1 1 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 11 PY 2007 VL 104 IS 37 BP 14753 EP 14758 DI 10.1073/pnas.0705201104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 211GT UT WOS:000249513000038 PM 17785425 ER PT J AU Shrank, WH Agnew-Blais, J Choudhry, NK Wolf, MS Kesselheim, AS Avorn, J Shekelle, P AF Shrank, William H. Agnew-Blais, Jessica Choudhry, Niteesh K. Wolf, Michael S. Kesselheim, Aaron S. Avorn, Jerry Shekelle, Paul TI The variability and quality of medication container labels SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PRESCRIPTION DRUG LABELS; READABILITY; FORMAT; COMPREHENSION; LITERACY; ADULTS AB Background: Medication errors occur frequently, and poor medication labeling is cited as a potential cause. We assessed the format, content, and variability of prescription drug container labels dispensed in the community. Methods: Identically written prescriptions for 4 commonly used medications (atorvastatin calcium [Lipitor], alendronate sodium [ Fosamax], trimethoprim-sulfamethoxazole [Bactrim], and ibuprofen) were filled in 6 pharmacies (the 2 largest chains, 2 grocery stores, and 2 independent pharmacies) in 4 cities (Boston, Chicago, Los Angeles, and Austin [Texas]). Characteristics of the format and content of the main container label and auxiliary stickers were evaluated. Labels were coded independently by 2 abstractors, and differences were reconciled by consensus. Results: We evaluated 85 labels after excluding 11 ibuprofen prescriptions that were filled with over-the-counter containers that lacked labels printed at the pharmacy. The pharmacy name or logo was the most prominent item on 71 (84%) of the labels, with a mean font size of 13.6 point. Font sizes were smaller for medication instructions (9.3 point), medication name (8.9 point), and warning and instruction stickers (6.5 point). Color, boldfacing, and highlighting were most often used to identify the pharmacy and items most useful to pharmacists. While the content of the main label was generally consistent, there was substantial variability in the content of instruction and warning stickers from different pharmacies, and independent pharmacies were less likely to use such stickers (P < . 001). None of the ibuprofen containers were delivered with Food and Drug Administration-approved medication guides, as required by law. Conclusions: The format of most container labels emphasizes pharmacy characteristics and items frequently used by pharmacists rather than use instructions or medication warnings. The content of warning and instruction stickers is highly variable depending on the pharmacy selected. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02120 USA. Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Chicago, IL 60611 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. RP Shrank, WH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA. EM wshrank@partners.org RI Agnew-Blais, Jessica/L-9236-2015 OI Agnew-Blais, Jessica/0000-0002-0755-6867 NR 25 TC 44 Z9 46 U1 1 U2 4 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 10 PY 2007 VL 167 IS 16 BP 1760 EP 1765 DI 10.1001/archinte.167.16.1760 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 208TV UT WOS:000249343000009 PM 17846395 ER PT J AU Merrell, MA Wakchoure, S Lehenkari, PP Harris, KW Selander, KS AF Merrell, Melinda A. Wakchoure, Savita Lehenkari, Petri P. Harris, Kevin W. Selander, Katri S. TI Inhibition of the mevalonate pathway and activation of p38 MAP kinase are independently regulated by nitrogen-containing bisphosphonates in breast cancer cells SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Bisphosphonates; p38; mevalonate pathway; cell cycle ID ADJUVANT CLODRONATE TREATMENT; RANDOMIZED CONTROLLED-TRIAL; INDUCED GROWTH-INHIBITION; HUMAN-MELANOMA CELLS; IN-VITRO; ZOLEDRONIC ACID; SKELETAL METASTASES; MEMBRANE LOCALIZATION; PROTEIN PRENYLATION; MESOTHELIOMA CELLS AB Bisphosphonates are widely used inhibitors of bone resorption. They also inhibit the growth of various cancer cells in vitro, but the clinical significance of this effect is unclear. The cancer growth inhibitory effects of nitrogen-containing bisphosphonates, (i.e. zoledronate) have been attributed to their ability to inhibit the mevalonate pathway. We have shown that bisphosphonates also induce p38 activation, which signals resistance against the drug-induced growth inhibition through an unknown mechanism. We show here that zoledronate induces a G1/S cell cycle arrest in human MDA-MB-231 breast cancer cells. Furthermore, p38 inhibitor augments bisphosphonate-induced growth inhibition by inducing an additional G2-phase cell cycle arrest. We also show that the nitrogen-containing bisphosphonate-induced effects on p38 phosphorylation occur before accumulation of unprenylated Rap1A or Rac1 activation. Geranylgeranyl pyrophosphate, an end-product of the mevalonate pathway, reversed the accumulation of unprenylated Rap1A but not phosphorylation of p38. Geranylgeranyl pyrophosphate also reversed n-BP induced growth inhibition, but the completeness of this reversal was nitrogen-containing bisphosphonate concentration dependent. Also mevastatin induced the accumulation of unprenylated Rap I A, but it did not induce p38 phosphorylation. In conclusion, our results suggest that in addition to the previously reported effects on apoptosis, nitrogen-containing bisphosphonates also inhibit the growth of MDA-MB-231 breast cancer cells by inducing G1/S cell cycle arrest. The bisphosphonate-induced p38 activation signals for resistance against these drugs, by promoting progression through the G2/M-checkpoint. Of these pathways only growth inhibition is mediated via inhibition of the mevalonate pathway in MDA-MB-231 cells. Combining p38 inhibitors with bisphosphonates may result in increased anti-cancer efficacy. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Alabama, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. Oulu Univ, Clin Res Ctr, Dept Surg, Oulu, Finland. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Selander, KS (reprint author), Univ Alabama, Dept Med, Div Hematol Oncol, WTI T558,1824 6th Ave S, Birmingham, AL 35294 USA. EM Katri.Selander@ccc.uab.edu RI Lehenkari, Petri/O-3009-2016 OI Lehenkari, Petri/0000-0002-0055-5183 NR 45 TC 28 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD SEP 10 PY 2007 VL 570 IS 1-3 BP 27 EP 37 DI 10.1016/j.ejphar.2007.05.075 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 208BP UT WOS:000249295100004 PM 17640631 ER PT J AU Duda, DG Jain, RK Willett, CG AF Duda, Dan G. Jain, Rakesh K. Willett, Christopher G. TI Antiangiogenics: The potential role of integrating this novel treatment modality with chemoradiation for solid cancers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER; TYROSINE KINASE INHIBITOR; RENAL-CELL CARCINOMA; PHASE-I TRIAL; VEGF RECEPTOR INHIBITOR; HUMAN TUMOR XENOGRAFTS; RECTAL-CANCER; VASCULAR NORMALIZATION; RADIATION-THERAPY AB Although still in very early stages of clinical development, the combination of antiangiogenics with contemporary chemoradiotherapy regimens has emerged as a feasible and promising approach to many cancers. We review the rationale and the current understanding of antiangiogenics and their therapeutic potential in combination with chemoradiotherapy. Finally, we offer a perspective on future research directions aimed at making this complex therapeutic approach successful in the clinic. C1 Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Duda, DG (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Box 3085, Durham, NC 27710 USA. EM duda@steele.mgh.harvard.edu; christopher.willett@duke.edu FU NCI NIH HHS [R21 CA099237, P01 CA080124, P01 CA080124-08, P01 CA80124, R01 CA115767, R01 CA115767-03, R21 CA099237-02] NR 65 TC 92 Z9 96 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 2007 VL 25 IS 26 BP 4033 EP 4042 DI 10.1200/JCO.2007.11.3985 PG 10 WC Oncology SC Oncology GA 233EK UT WOS:000251073000002 PM 17827451 ER PT J AU Stupp, R Hegi, ME Gilbert, MR Chakravarti, A AF Stupp, Roger Hegi, Monika E. Gilbert, Mark R. Chakravarti, Arnab TI Chemoradiotherapy in malignant glioma: Standard of care and future directions SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID PHASE-II TRIAL; GROWTH-FACTOR RECEPTOR; DIAGNOSED GLIOBLASTOMA-MULTIFORME; FARNESYL TRANSFERASE INHIBITORS; GYNECOLOGIC-ONCOLOGY-GROUP; CELL LUNG-CANCER; LOW-GRADE GLIOMA; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; RECURRENT GLIOBLASTOMA; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE AB Glioma has been considered resistant to chemotherapy and radiation. Recently, concomitant and adjuvant chemoradiotherapy with temozolomide has become the standard treatment for newly diagnosed glioblastoma. Conversely (neo-) adjuvant PCV (procarbazine, lomustine, vincristine) failed to improve survival in the more chemoresponsive tumor entities of anaplastic oligoastrocytoma and oligodendroglioma. Preclinical investigations suggest synergism or additivity of radiotherapy and temozolomide in glioma cell lines. Although the relative contribution of the concomitant and the adjuvant chemotherapy, respectively, cannot be assessed, the early introduction of chemotherapy and the simultaneous administration with radiotherapy appear to be key for the improvement of outcome. Epigenetic inactivation of the DNA repair enzyme methylguanine methyltransferase (MGMT) seems to be the strongest predictive marker for outcome in patients treated with alkylating agent chemotherapy. Patients whose tumors do not have MGMT promoter methylation are less likely to benefit from the addition of temozolomide chemotherapy and require alternative treatment strategies. The predictive value of MGMT gene promoter methylation is being validated in ongoing trials aiming at overcoming this resistance by a dose-dense continuous temozolomide administration or in combination with MGMT inhibitors. Understanding of molecular mechanisms allows for rational targeting of specific pathways of repair, signaling, and angiogenesis. The addition of tyrosine kinase inhibitors vatalanib (PTK787) and vandetinib (ZD6474), the integrin inhibitor cilengitide, the monoclonal antibodies bevacizumab and cetuximab, the mammalian target of rapamycin inhibitors temsirolimus and everolimus, and the protein kinase C inhibitor enzastaurin, among other agents, are in clinical investigation, building on the established chemoradiotherapy regimen for newly diagnosed glioblastoma. C1 CHU Vaudois, Dept Neurosurg, Lab Tumor Biol & Genet, CH-1011 Lausanne, Switzerland. Univ Lausanne, CH-1011 Lausanne, Switzerland. Multidisciplinary Oncol Ctr, Lausanne, Switzerland. Swiss Inst Expt Canc Res, Natl Ctr Competence Res Mol Oncol, CH-1066 Epalinges, Switzerland. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Lab Mol & Cellular Radiat Neuro, Boston, MA USA. RP Stupp, R (reprint author), CHU Vaudois, Dept Neurosurg, Lab Tumor Biol & Genet, Rue Bugnon 46, CH-1011 Lausanne, Switzerland. EM roger.stupp@chuv.ch RI leng, xianwei/F-9073-2011; Hegi, Monika/O-4796-2015; Gilbert, Mark/J-7494-2016 OI Hegi, Monika/0000-0003-0855-6495; Gilbert, Mark/0000-0003-2556-9722 NR 100 TC 246 Z9 258 U1 2 U2 28 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 2007 VL 25 IS 26 BP 4127 EP 4136 DI 10.1200/JCO.2007.11.8554 PG 10 WC Oncology SC Oncology GA 233EK UT WOS:000251073000014 PM 17827463 ER PT J AU Chen, YT Collins, LL Uno, H Chou, SM Meshul, CK Chang, SS Chang, C AF Chen, Yei-Tsung Collins, Loretta L. Uno, Hideo Chou, Samuel M. Meshul, Charles K. Chang, Shu-Shi Chang, Chawnshang TI Abnormal cerebellar cytoarchitecture and impaired inhibitory signaling in adult mice lacking TR4 orphan nuclear receptor SO BRAIN RESEARCH LA English DT Article DE testicular orphan nuclear receptor 4; cerebellar atrophy; locomotor ID NEUROTROPHIC FACTOR; BIDIRECTIONAL REGULATION; MOLECULAR-CLONING; GENETIC-CONTROL; DOWN-REGULATION; MUTANT MICE; MOUSE LINES; SUPERFAMILY; BEHAVIOR; ALPHA AB Since testicular orphan nuclear receptor 4 (TR4) was cloned, its physiological functions remain largely unknown. In this study, the TR4 knockout (TR4(-/-)) mouse model was used to investigate the role of TR4 in the adult cerebellum. Behaviorally, these null mice exhibit unsteady gait, as well as involuntary postural and kinetic movements, indicating a disturbance of cerebellar function. In the TR4(-/-) brain, cerebellar restricted hypoplasia is severe and cerebellar vermal lobules VI and VII are underdeveloped, while no structural alterations in the cerebral cortex are observed. Histological analysis of the TR4(-/-) cerebellar cortex reveals reductions in granule cell density, as well as a decreased number of parallel fiber boutons that are enlarged in size. Further analyses reveal that the levels of GABA and GAD are decreased in both Purkinje cells and interneurons of the TR4(-/-) cerebellum, suggesting that the inhibitory circuits signaling within and from the cerebellum may be perturbed. In addition, in the TR4(-/-) cerebellum, immunoreactivity of GluR2/3 was reduced in Purkinje cells, but increased in the deep cerebellar nuclei. Together, these results suggest that the behavioral phenotype of TR4(-/-) mice may result from disrupted inhibitory pathways in the cerebellum. No progressive atrophy was observed at various adult stages in the TR4(-/-) brain, therefore the disturbances most likely originate from a failure to establish proper connections between principal neurons in the cerebellum during development. (C) 2007 Elsevier B.V. All rights reserved. C1 Univ Rochester, Dept Pathol, George Whipple Lab Canc Res, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Dept Urol, Rochester, NY 14642 USA. Univ Rochester, Ctr Canc, Dept Radiat Oncol, Rochester, NY 14642 USA. Univ Rochester, Ctr Canc, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurol, Boston, MA 02114 USA. Univ Rochester, Dept Environm Med, Rochester, NY 14642 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53708 USA. Norris ALS Neuromuscular Res Inst, San Francisco, CA 94115 USA. Oregon Hlth & Sci Univ, VA Med Ctr, Dept Behav Neurosci, Res Serv, Portland, ME USA. Chinese Med Univ, Dept Neurosci, Taichung, Taiwan. RP Chang, C (reprint author), Univ Rochester, Dept Pathol, George Whipple Lab Canc Res, 601 Elmwood Ave, Rochester, NY 14642 USA. EM chang@urmc.rochester.edu FU NIDDK NIH HHS [DK 56984, R01 DK063212, R01 DK056984, R01 DK063212-04, DK 63212, R01 DK063212-03, R01 DK056984-03, R01 DK056984-04] NR 56 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 7 PY 2007 VL 1168 BP 72 EP 82 DI 10.1016/j.brainres.2007.06.069 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 218UX UT WOS:000250041700009 PM 17706948 ER PT J AU Weiner, L Han, R Scicchitano, BM Li, J Hasegawa, K Grossi, M Lee, D Brissette, JL AF Weiner, Lorin Han, Rong Scicchitano, Bianca M. Li, Jian Hasegawa, Kiyotaka Grossi, Maddalena Lee, David Brissette, Janice L. TI Dedicated epithelial recipient cells determine pigmentation patterns SO CELL LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; NORMAL HUMAN MELANOCYTES; SERUM-FREE MEDIUM; TERMINAL DIFFERENTIATION; NUDE GENE; HAIR FOLLICLE; KERATIN GENE; EPIDERMAL MELANOBLASTS; HUMAN SKIN; EXPRESSION AB Mammals generate external coloration via dedicated pigment-producing cells but arrange pigment into patterns through mechanisms largely unknown. Here, using mice as models, we show that patterns ultimately emanate from dedicated pigment-receiving cells. These pigment recipients are epithelial cells that recruit melanocytes to their position in the skin and induce the transfer of melanin. We identify Foxn1 (a transcription factor) as an activator of this "pigment recipient phenotype" and Fgf2 (a growth factor and Foxn1 target) as a signal released by recipients. When Foxn1-and thus dedicated recipients-are redistributed in the skin, new patterns of pigmentation develop, suggesting a mechanism for the evolution of coloration. We conclude that recipients provide a cutaneous template or blueprint that instructs melanocytes where to place pigment. As Foxn1 and Fgf2 also modulate epithelial growth and differentiation, the Foxn1 pathway should serve as a nexus coordinating cell division, differentiation, and pigmentation. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. RP Brissette, JL (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM jbrissette@partners.org OI Han, Rong/0000-0002-5766-8277; Scicchitano, Bianca Maria/0000-0002-9599-6642 FU NIAMS NIH HHS [AR045284, R01 AR045284-10, R01 AR045284] NR 58 TC 56 Z9 59 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 7 PY 2007 VL 130 IS 5 BP 932 EP 942 DI 10.1016/j.cell.2007.07.024 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 212GI UT WOS:000249581500023 PM 17803914 ER PT J AU Forbes, A Wadehra, M Mareninov, S Morales, S Shimazaki, K Gordon, LK Braun, J AF Forbes, Ashley Wadehra, Madhuri Mareninov, Sergei Morales, Shawn Shimazaki, Kaori Gordon, Lynn K. Braun, Jonathan TI The tetraspan protein EMP2 regulates expression of caveolin-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPITHELIAL MEMBRANE PROTEIN-2; HUMAN BREAST-CANCER; ONCOGENICALLY TRANSFORMED-CELLS; ANCHORAGE-INDEPENDENT GROWTH; HIGH-GRADE OSTEOSARCOMA; SURFACE EXPRESSION; PLASMA-MEMBRANE; IN-VIVO; TYROSINE PHOSPHORYLATION; ENDOPLASMIC-RETICULUM AB Caveolin-1 is the primary component of caveolae and functions in a variety of intracellular activities, including membrane trafficking and signal transduction. EMP2(epithelial membrane protein 2) is a tetraspan protein recently identified as a novel regulator of caveolin-1 expression. In this study, we analyzed the mechanism of EMP2-mediated caveolin-1 regulation. In NIH 3T3 cells and in the human retinal pigment epithelium cell line (ARPE-19), EMP2 regulates caveolin-1 transcription and more substantially its protein levels. EMP2-mediated down-regulation of caveolin-1 does not affect caveolin-1 translational efficiency, phosphorylation, or proteasome-mediated degradation. Analysis of caveolin-1 protein half-life indicates the EMP2-mediated loss of caveolin-1 occurs rapidly. Protease inhibition and laser confocal microscopy associates this fate with specific intracellular compartmentalization, including early lysosomal delivery. These findings elucidate a new mechanism of caveolin-1 regulation and define an additional role for EMP2 as a key regulator of cell membrane composition. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Dept Surg, Los Angeles, CA 90099 USA. Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Ctr Hlth Sci 13 222, Los Angeles, CA 90095 USA. RP Braun, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Ctr Hlth Sci 13 222, Los Angeles, CA 90095 USA. EM jbraun@mednet.ucla.edu FU NCI NIH HHS [CA16042, P30 CA016042, CA9120]; NIAID NIH HHS [AI52031]; NICHD NIH HHS [R03 HD048540, HD48540]; NIGMS NIH HHS [GM7185] NR 59 TC 20 Z9 21 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 7 PY 2007 VL 282 IS 36 AR 26542 DI 10.1074/jbc.M702117200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 207GM UT WOS:000249239600058 PM 17609206 ER PT J AU Chakraborty, T Chowdhury, D Keyes, A Jani, A Subrahmanyam, R Ivanova, I Sen, R AF Chakraborty, Tirtha Chowdhury, Dipanjan Keyes, Amanda Jani, Anant Subrahmanyam, Ramesh Ivanova, Irina Sen, Ranjan TI Repeat organization and epigenetic regulation of the D-H-C-mu domain of the immunoglobulin heavy-chain gene locusi SO MOLECULAR CELL LA English DT Article ID CHROMATIN DOMAINS; V(D)J RECOMBINATION; HISTONE; HETEROCHROMATIN; METHYLATION; REARRANGEMENTS; BOUNDARIES; ELEMENT; SEGMENT; FETAL AB The first steps of murine immunoglobulin heavy-chain (IgH) gene recombination take place within a chromosomal domain that contains diversity (D-H) and joining (J(H)) gene segments, but not variable (V-H) gene segments. Here we show that the chromatin state of this domain is markedly heterogeneous. Specifically, only 5'- and 3'-most D-H gene segments carry active chromatin modifications, whereas intervening D(H)s are associated with heterochromatic marks that are maintained by ongoing histone deacetylation. The intervening D(H)s form part of a tandemly repeated sequence that expresses tissue-specific, antisense oriented transcripts. We propose that the intervening DH genes are actively suppressed by repeat-induced epigenetic silencing, which is reflected in their infrequent representation in DJ(H) junctions compared to the flanking D-H genes. C1 NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Yale Univ, Dept Chem Engn, New Haven, CT 06511 USA. Yale Univ, Sch Med, Program Immunol, New Haven, CT 06510 USA. RP Sen, R (reprint author), NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. EM rs465z@nih.gov RI Subrahmanyam, Ramesh/K-5503-2012 FU Intramural NIH HHS; NIGMS NIH HHS [GM38925] NR 31 TC 56 Z9 56 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD SEP 7 PY 2007 VL 27 IS 5 BP 842 EP 850 DI 10.1016/j.molcel.2007.07.010 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 216AK UT WOS:000249849900013 PM 17803947 ER PT J AU Olavarria, JF van Brederode, JFM Spain, WJ AF Olavarria, J. F. van Brederode, J. F. M. Spain, W. J. TI Retinal influences induce bidirectional changes in the kinetics of N-methyl-D-aspartate receptor-mediated responses in striate cortex cells during postnatal development SO NEUROSCIENCE LA English DT Article DE striate cortex; interhemispheric callosal commissure; maps; NMDA receptor; plasticity; ifenprodil ID OCULAR DOMINANCE PLASTICITY; HETEROMERIC NMDA RECEPTORS; NR2A SUBUNIT EXPRESSION; RAT VISUAL-CORTEX; THALAMOCORTICAL SYNAPSES; IFENPRODIL SENSITIVITY; FUNCTIONAL-PROPERTIES; CALLOSAL CONNECTIONS; SYNAPTIC PLASTICITY; ENUCLEATED RATS AB Development of the visual callosal projection in rodents goes through an early critical period, from postnatal day (P) 4 to P6, during which retinal input specifies the blueprint for normal topographic connections, and a subsequent period of progressive pathway maturation that is largely complete by the time the eyes open, around P13. This study tests the hypothesis that these developmental stages correlate with age-related changes in the kinetics of synaptic responses mediated by the N-methyl-D-aspartate subclass of glutamate receptors (NMDARs). We used an in vitro slice preparation to perform whole-cell recordings from retrogradely-labeled visual callosal cells, as well from cortical cells with unknown projections. We analyzed age-related changes in the decay time constant of evoked as well as spontaneous excitatory postsynaptic currents mediated by N-methyl-D-aspartate subclass of glutamate receptors (NMDAR-EPSCs) in slices from normal pups and pups enucleated at different postnatal ages. In normal pups we found that the decay time constant of NMDAR-EPSCs increases starting at about P6 and decreases by about P13. In contrast, these changes were not observed in rats enucleated at birth. However, by delaying the age at which enucleation was performed we found that the presence of the eyes until P6, but not until P4, is sufficient for inducing slow NMDAR-EPSC kinetics during the second postnatal week, as observed in normal pups. These results provide evidence that the eyes exert a bidirectional effect on the kinetics of NMDARs: during a P4-P6 critical period, retinal influences induce processes that slow down the kinetics of NMDAR-EPSCs, while, near the age of eye opening, retinal input induces a sudden acceleration of NMDAR-EPSC kinetics. These findings suggest that the retinally-driven processes that specify normal callosal topography during the P4-P6 time window also induce an increase in the decay time constant of NMDAR-EPSCs. This increase in response kinetics may play an important role in the maturation of cortical topographic maps after P6. Using ifenprodil, a noncompetitive NR213-selective blocker, we obtained evidence that although NR1/NR2B diheteromeric receptors contribute to evoked synaptic responses in both normal and enucleated animals, they are not primarily responsible for either the age-related changes in the kinetics of NMDAR-mediated responses, or the effects that bilateral enucleation has on the kinetics of NMDAR-EPSCs. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Olavarria, JF (reprint author), Univ Washington, Dept Psychol, Box 351525, Seattle, WA 98195 USA. EM jaime@u.washington.edu FU BLRD VA [I01 BX000386]; NEI NIH HHS [EY016045]; PHS HHS [34769] NR 57 TC 4 Z9 5 U1 0 U2 0 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 7 PY 2007 VL 148 IS 3 BP 683 EP 699 DI 10.1016/j.neuroscience.2007.07.005 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 216LG UT WOS:000249878900009 PM 17706364 ER PT J AU Kanoulas, E Aslam, JA Sharp, GC Berbeco, RI Nishioka, S Shirato, H Jiang, SB AF Kanoulas, E. Aslam, J. A. Sharp, G. C. Berbeco, R. I. Nishioka, S. Shirato, H. Jiang, S. B. TI Derivation of the tumor position from external respiratory surrogates with periodical updating of the internal/external correlation SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID REAL-TIME TUMOR; DYNAMIC MULTILEAF COLLIMATOR; RADIATION-THERAPY SMART; LUNG-TUMORS; RADIOTHERAPY TREATMENT; TRACKING RADIOTHERAPY; MOVEMENT COMPENSATION; GATED RADIOTHERAPY; MOTION TRACKING; DELIVERY AB In this work we develop techniques that can derive the tumor position from external respiratory surrogates (abdominal surface motion) through periodically updated internal/external correlation. A simple linear function is used to express the correlation between the tumor and surrogate motion. The function parameters are established during a patient setup session with the tumor and surrogate positions simultaneously measured at a 30 Hz rate. During treatment, the surrogate position, constantly acquired at 30 Hz, is used to derive the tumor position. Occasionally, a pair of radiographic images is acquired to enable the updating of the linear correlation function. Four update methods, two aggressive and two conservative, are investigated: (A1) shift line through the update point; (A2) re-fit line through the update point; (C1) re-fit line with extra weight to the update point; (C2) minimize the distances to the update point and previous line fit point. In the present study of eight lung cancer patients, tumor and external surrogate motion demonstrate a high degree of linear correlation which changes dynamically over time. It was found that occasionally updating the correlation function leads to more accurate predictions than using external surrogates alone. In the case of high imaging rates during treatment (greater than 2 Hz) the aggressive update methods (A1 and A2) are more accurate than the conservative ones (C1 and C2). The opposite is observed in the case of low imaging rates. C1 Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. NTT Hosp, Dept Radiol, Sapporo, Hokkaido, Japan. Hokkaido Univ, Sch Med, Dept Radiat Med, Sapporo, Hokkaido 060, Japan. Univ Calif San Diego, Dept Radiat Oncol, La Jolla, CA 92093 USA. RP Kanoulas, E (reprint author), Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA. EM ekanou@ccs.neu.edu RI Shirato, Hiroki/A-7068-2010 NR 43 TC 32 Z9 33 U1 1 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 7 PY 2007 VL 52 IS 17 BP 5443 EP 5456 DI 10.1088/0031-9155/52/17/023 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 205CE UT WOS:000249089900023 PM 17762097 ER PT J AU Singh, BN Connolly, SJ Crijns, HJGM Roy, D Kowey, PR Capucci, A Radzik, D Aliot, EM Hohnloser, SH AF Singh, Bramah N. Connolly, Stuart J. Crijns, Harry J. G. M. Roy, Denis Kowey, Peter R. Capucci, Alessandro Radzik, David Aliot, Etienne M. Hohnloser, Stefan H. CA EURIDIS Investigators ADONIS Investigators TI Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONTROLLED CLINICAL-TRIAL; AMIODARONE-LIKE AGENT; ANTIARRHYTHMIC-DRUGS; PROGNOSTIC FACTORS; SR-33589; EFFICACY; THERAPY; HEART; ARRHYTHMIAS; MECHANISMS AB Background Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects. Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects. Methods In two identical multicenter, double-blind, randomized trials, one conducted in Europe (ClinicalTrials.gov number, NCT000259428) and one conducted in the United States, Canada, Australia, South Africa, and Argentina (termed the non-European trial, NCT000259376), we evaluated the efficacy of dronedarone, with 828 patients receiving 400 mg of the drug twice daily and 409 patients receiving placebo. Rhythm was monitored transtelephonically on days 2, 3, and 5; at 3, 5, 7, and 10 months; during recurrence of arrhythmia; and at nine scheduled visits during a 12-month period. The primary end point was the time to the first recurrence of atrial fibrillation or flutter. Results In the European trial, the median times to the recurrence of arrhythmia were 41 days in the placebo group and 96 days in the dronedarone group (P=0.01). The corresponding durations in the non-European trial were 59 and 158 days (P=0.002). At the recurrence of arrhythmia in the European trial, the mean (+/-SD) ventricular rate was 117.5+/-29.1 beats per minute in the placebo group and 102.3+/-24.7 beats per minute in the dronedarone group (P<0.001); the corresponding rates in the non-European trial were 116.6+/-31.9 and 104.6+/-27.1 beats per minute (P<0.001). Rates of pulmonary toxic effects and of thyroid and liver dysfunction were not significantly increased in the dronedarone group. Conclusions Dronedarone was significantly more effective than placebo in maintaining sinus rhythm and in reducing the ventricular rate during recurrence of arrhythmia. C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. Univ Hamilton, Hamilton, ON, Canada. Univ Maastricht, Maastricht, Netherlands. Univ Montreal, Montreal, PQ, Canada. Lankenau Hosp & Inst Med Res, Philadelphia, PA USA. Osped Clin, Taverna, Italy. Sanofi Aventis, Paris, France. Cent Hosp, Nancy, France. Univ Frankfurt, D-6000 Frankfurt, Germany. RP Singh, BN (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Div Cardiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM bsingh@ucla.edu NR 39 TC 357 Z9 382 U1 1 U2 7 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 6 PY 2007 VL 357 IS 10 BP 987 EP 999 DI 10.1056/NEJMoa054686 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 206VK UT WOS:000249210800005 PM 17804843 ER PT J AU Kim, JW Waldman, ID Faraone, SV Biederman, J Doyle, AE Purcell, S Arbeitman, L Fagerness, J Sklar, P Smoller, JW AF Kim, Jang Woo Waldman, Irwin D. Faraone, Stephen V. Biederman, Joseph Doyle, Alysa E. Purcell, Shaun Arbeitman, Lori Fagerness, Jesen Sklar, Pamela Smoller, Jordan W. TI Investigation of parent-of-origin effects in ADHD candidate genes SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE attention deficit hyperactivity disorder (ADHD) ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; 5-HT1B RECEPTOR GENE; BIPOLAR DISORDER; ASSOCIATION; SUSCEPTIBILITY; LINKAGE; TRANSMISSION; SNAP-25; ALLELES AB Attention deficit hyperactivity disorder (ADHD) is a common early-onset childhood disorder with a strong genetic component. Results from previous studies have suggested that there may be a parent-of-origin effect for ADHD candidate genes. In particular, a recent investigation identified a pattern of paternal over-transmission of risk alleles for nine ADHD candidate genes. We examined this phenomenon in a sample of 291 trios for five genes previously associated with ADHD (HTR1B, SNAP-25, DRD5, DAT1, and BDNF). Using a dense map of markers and two analytic methods in this relatively large family-based sample, we do not find any evidence for significant paternal over-transmission of risk alleles in these candidate loci. Thus, we conclude that a substantial parent-of-origin effect is unlikely for these leading ADHD candidate genes. (c) 2007 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, Boston, MA 02114 USA. Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Res, Boston, MA USA. RP Kim, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, 185 Cambridge St, Boston, MA 02114 USA. EM jwkim@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [HD37999, HD37694]; NIMH NIH HHS [MH66877] NR 21 TC 19 Z9 20 U1 2 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 2007 VL 144B IS 6 BP 776 EP 780 DI 10.1002/ajmg.b.30519 PG 5 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 207HO UT WOS:000249242400011 PM 17427194 ER PT J AU Kim, JW Biederman, J Arbeitman, L Fagerness, J Doyle, AE Petty, C Perlis, RH Purcell, S Smoller, JW Faraone, SV Sklar, P AF Kim, J. W. Biederman, J. Arbeitman, L. Fagerness, J. Doyle, A. E. Petty, C. Perlis, R. H. Purcell, S. Smoller, J. W. Faraone, S. V. Sklar, P. TI Investigation of variation in SNAP-25 and ADHD and relationship to co-morbid major depressive disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE ADHD; association; co-morbid major depressive disorder; SNAP-25 ID ATTENTION-DEFICIT HYPERACTIVITY; DEFICIT/HYPERACTIVITY DISORDER; BIPOLAR DISORDER; FAMILIAL SUBTYPE; RISK-FACTORS; CONDUCT DISORDER; ASSOCIATION; DOPAMINE; GENETICS; COMORBIDITY AB Synaptosomal-associated protein of 25 kDa (SNAP-25), a protein involved in presynaptic neurotransmitter release, is a candidate gene for attention deficit/hyperactivity disorder (ADHD). Previous investigators have reported association initially with two single nucleotide polymorphisms (SNPs) (rs3746544, rs1051312) and their associated haplotypes. Subsequently, additional SNPs across the region were also reported to be associated with ADHD. We attempted to replicate these observations in a sample of 229 families with ADHD offspring by genotyping 61 SNPs spanning the region containing SNAP-25. A single SNP (rs3787283) which is in strong linkage disequilibrium. (LD) with rs3746544 and rs1051312 (D'= 0.89-0.94) resulted in a nominally significant association (P = 0.002). When we pooled our data with those from prior studies, results were modestly significant for rs3746544 (P = 0.048) and rs6077690 (P = 0.031). As an attempt to determine if specific ADHD-related phenotypes may be more relevant to SNAP-25 than the categorical diagnosis, we carried out exploratory subgroup analysis in our ADHD sample according to co-morbid status. We found the strongest association result in the ADHD patients with co-morbid major depressive disorder (MDD). Six SNPs were nominally associated with the ADHD and co-morbid MDD cases (P = 0.012-0.045). Furthermore, a haplotype block located 11 kb 3' of the gene showed positive evidence for association with this phenotype (global P=0.013). In conclusion, we report some evidence supporting the association of previously implicated SNPs (rs3746544, rs1.051312) of SNAP-25 to ADHD. We further suggest that comorbidity with MDD may enhance detection of the association between SNAP-25 and ADHD. (c) 2007 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Res, Boston, MA USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Sklar, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, 185 Cambridge St, Boston, MA 02114 USA. EM sklar@psych.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [HD37694]; NIDDK NIH HHS [DK37999]; NIMH NIH HHS [MH66877] NR 52 TC 41 Z9 44 U1 3 U2 5 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 2007 VL 144B IS 6 BP 781 EP 790 DI 10.1002/ajmg.b.30522 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 207HO UT WOS:000249242400012 PM 17455213 ER PT J AU Volpp, KG Rosen, AK Rosenbaum, PR Romano, PS Even-Shoshan, O Wang, YL Bellini, L Behringer, T Silber, JH AF Volpp, Kevin G. Rosen, Amy K. Rosenbaum, Paul R. Romano, Patrick S. Even-Shoshan, Orit Wang, Yanli Bellini, Lisa Behringer, Tiffany Silber, Jeffrey H. TI Mortality among hospitalized Medicare beneficiaries in the first 2 years following ACGME resident duty hour reform SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY-OF-CARE; WORK HOURS; ADMINISTRATIVE DATA; SLEEP-DEPRIVATION; PATIENT SAFETY; COMORBIDITY MEASURES; PERFORMANCE; ICD-9-CM; REGULATIONS; INFORMATION AB Context The Accreditation Council for Graduate Medical Education (ACGME) implemented duty hour regulations for physicians-in-training throughout the United States on July 1, 2003. The association of duty hour reform with mortality among patients in teaching hospitals nationally has not been well established. Objective To determine whether the change in duty hour regulations was associated with relative changes in mortality among Medicare patients in hospitals of different teaching intensity. Design, Setting, and Patients An observational study of all unique Medicare patients (N= 8 529 595) admitted to short-term, acute-care, general US nonfederal hospitals ( N= 3321) using interrupted time series analysis with data from July 1, 2000, to June 30, 2005. All Medicare patients had principal diagnoses of acute myocardial infarction, congestive heart failure, gastrointestinal bleeding, or stroke or a diagnosis related group classification of general, orthopedic, or vascular surgery. Logistic regression was used to examine the change in mortality for patients in more vs less teaching-intensive hospitals before (academic years 2000-2003) and after (academic years 20032005) duty hour reform, adjusting for patient comorbidities, common time trends, and hospital site. Main Outcome Measure All-location mortality within 30 days of hospital admission. Results In medical and surgical patients, no significant relative increases or decreases in the odds of mortality for more vs less teaching-intensive hospitals were observed in either postreform year 1 (combined medical conditions group: odds ratio [OR], 1.03; 95% confidence interval [Cl], 0.98-1.07; and combined surgical categories group: OR, 1.05; 95% Cl, 0.98-1.12) or postreform year 2 ( combined medical conditions group: OR, 1.03; 95% Cl, 0.99-1.08; and combined surgical categories group: OR, 1.01; 95% Cl, 0.95-1.08) compared with the prereform years. The only condition for which there was a relative increase in mortality in more teaching-intensive hospitals postreform was stroke, but this association preceded the onset of duty hour reform. Compared with nonteaching hospitals, the most teaching-intensive hospitals had an absolute change in mortality from prereform year 1 to postreform year 2 of 0.42 percentage points (4.4% relative increase) for patients in the combined medical conditions group and 0.05 percentage points (2.3% relative increase) for patients in the combined surgical categories group, neither of which were statistically significant. Conclusion The ACGME duty hour reform was not associated with either significant worsening or improvement in mortality for Medicare patients in the first 2 years after implementation. C1 Vet Adm Hosp, Philadelphia Vet Affairs Med Ctr, CHERP, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Univ Calif Davis Sch Med, Div Gen Med, Sacramento, CA 95817 USA. Univ Calif Davis Sch Med, Ctr Healthcare Policy & Res, Sacramento, CA 95817 USA. RP Volpp, KG (reprint author), Vet Adm Hosp, Philadelphia Vet Affairs Med Ctr, CHERP, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu RI Rosenbaum, Paul/H-8687-2012; Romano, Patrick/N-4225-2014 OI Romano, Patrick/0000-0001-6749-3979 FU NHLBI NIH HHS [R01 HL082637] NR 54 TC 202 Z9 203 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 5 PY 2007 VL 298 IS 9 BP 975 EP 983 DI 10.1001/jama.298.9.975 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 206OH UT WOS:000249192300012 PM 17785642 ER PT J AU Volpp, KG Rosen, AK Rosenbaum, PR Romano, PS Even-Shoshan, O Canamucio, A Bellini, L Behringer, T Silber, JH AF Volpp, Kevin G. Rosen, Amy K. Rosenbaum, Paul R. Romano, Patrick S. Even-Shoshan, Orit Canamucio, Anne Bellini, Lisa Behringer, Tiffany Silber, Jeffrey H. TI Mortality among patients in VA hospitals in the first 2 years following ACGME resident duty hour reform SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY-OF-CARE; WORK HOURS; ADMINISTRATIVE DATA; COMORBIDITY MEASURES; VETERAN POPULATION; SAFETY; ICD-9-CM; LIMITS; ASCERTAINMENT; REGULATIONS AB Context Limitations in duty hours for physicians-in-training in the United States were established by the Accreditation Council for Graduate Medical Education (ACGME) and implemented on July 1, 2003. The association of these changes with mortality among hospitalized patients has not been well established. Objective To determine whether the change in duty hour regulations was associated with relative changes in mortality in hospitals of different teaching intensity within the US Veterans Affairs (VA) system. Design, Setting, and Patients An observational study of all unique patients (N=318 636) admitted to acute-care VA hospitals (N=131) using interrupted time series analysis with data from July 1, 2000, to June 30, 2005. All patients had principal diagnoses of acute myocardial infarction (AMI), congestive heart failure, gastrointestinal bleeding, or stroke or a diagnosis related group classification of general, orthopedic, or vascular surgery. Logistic regression was used to examine the change in mortality for patients in more vs less teaching-intensive hospitals before ( academic years 2000-2003) and after (academic years 2003-2005) duty hour reform, adjusting for patient comorbidities, common time trends, and hospital site. Main Outcome Measure All-location mortality within 30 days of hospital admission. Results In postreform year 1, no significant relative changes in mortality were observed for either medical or surgical patients. In postreform year 2, the odds of mortality decreased significantly in more teaching-intensive hospitals for medical patients only. Comparing a hospital having a resident-to-bed ratio of 1 with a hospital having a resident-to-bed ratio of 0, the odds of mortality were reduced for patients with AMI (odds ratio [ OR], 0.48; 95% confidence interval [Cl], 0.33-0.71), for the 4 medical conditions together (OR, 0.74; 95% Cl, 0.61-0.89), and for the 3 medical conditions excluding AMI (OR, 0.79; 95% Cl, 0.63-0.98). Compared with hospitals in the 25th percentile of teaching intensity, there was an absolute improvement in mortality from prereform year 1 to postreform year 2 of 0.70 percentage points (11.1% relative decrease) and 0.88 percentage points (13.9% relative decrease) in hospitals in the 75th and 90th percentile of teaching intensity, respectively, for the combined medical conditions. Conclusions The ACGME duty hour reform was associated with significant relative improvement in mortality for patients with 4 common medical conditions in more teaching intensive VA hospitals in postreform year 2. No associations were identified for surgical patients. C1 Vet Adm Hosp, Philadelphia Vet Affairs Med Ctr, CHERP, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Univ Calif Davis Sch Med, Div Gen Med, Sacramento, CA USA. Univ Calif Davis Sch Med, Ctr Healthcare Policy & Res, Sacramento, CA USA. RP Volpp, KG (reprint author), Vet Adm Hosp, Philadelphia Vet Affairs Med Ctr, CHERP, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu RI Rosenbaum, Paul/H-8687-2012; Romano, Patrick/N-4225-2014 OI Romano, Patrick/0000-0001-6749-3979 FU NHLBI NIH HHS [R01 HL082637] NR 53 TC 165 Z9 166 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 5 PY 2007 VL 298 IS 9 BP 984 EP 992 DI 10.1001/jama.298.9.984 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 206OH UT WOS:000249192300013 PM 17785643 ER PT J AU Asch, DA Epstein, A Nicholson, S AF Asch, David A. Epstein, Andrew Nicholson, Sean TI Evaluating medical training programs by the quality of care delivered by their alumni SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MORTALITY-RATES C1 Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Yale Univ, Sch Publ Hlth, Div Hlth Policy & Adm, New Haven, CT USA. Cornell Univ, Dept Policy Anal & Management, Ithaca, NY USA. Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Asch, DA (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, 3641 Locust Walk, Philadelphia, PA 19104 USA. EM asch@wharton.upenn.edu NR 7 TC 7 Z9 7 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 5 PY 2007 VL 298 IS 9 BP 1049 EP 1051 DI 10.1001/jama.298.9.1049 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 206OH UT WOS:000249192300020 PM 17785650 ER PT J AU Rolland, M Nickle, DC Deng, W Frahm, N Brander, C Learn, GH Heckerman, D Jojic, N Jojic, V Walker, BD Mullins, JI AF Rolland, Morgane Nickle, David C. Deng, Wenjie Frahm, Nicole Brander, Christian Learn, Gerald H. Heckerman, David Jojic, Nebosja Jojic, Vladimir Walker, Bruce D. Mullins, James I. TI Recognition of HIV-1 Peptides by Host CTL Is Related to HIV-1 Similarity to Human Proteins SO PLOS ONE LA English DT Article AB Background. While human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes preferentially target specific regions of the viral proteome, HIV-1 features that contribute to immune recognition are not well understood. One hypothesis is that similarities between HIV and human proteins influence the host immune response, i.e., resemblance between viral and host peptides could preclude reactivity against certain HIV epitopes. Methodology/Principal Findings. We analyzed the extent of similarity between HIV-1 and the human proteome. Proteins from the HIV-1 B consensus sequence from 2001 were dissected into overlapping k-mers, which were then probed against a non-redundant database of the human proteome in order to identify segments of high similarity. We tested the relationship between HIV-1 similarity to host encoded peptides and immune recognition in HIV-infected individuals, and found that HIV immunogenicity could be partially modulated by the sequence similarity to the host proteome. ELISpot responses to peptides spanning the entire viral proteome evaluated in 314 individuals showed a trend indicating an inverse relationship between the similarity to the host proteome and the frequency of recognition. In addition, analysis of responses by a group of 30 HIV-infected individuals against 944 overlapping peptides representing a broad range of individual HIV-1B Nef variants, affirmed that the degree of similarity to the host was significantly lower for peptides with reactive epitopes than for those that were not recognized. Conclusions/Significance. Our results suggest that antigenic motifs that are scarcely represented in human proteins might represent more immunogenic CTL targets not selected against in the host. This observation could provide guidance in the design of more effective HIV immunogens, as sequences devoid of host-like features might afford superior immune reactivity. C1 [Rolland, Morgane; Nickle, David C.; Deng, Wenjie; Learn, Gerald H.; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Frahm, Nicole; Brander, Christian; Walker, Bruce D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Harvard Med Sch, Charlestown, MA USA. [Heckerman, David; Jojic, Nebosja; Jojic, Vladimir] Microsoft Res, Machine Learning & Appl Stat Grp, Redmond, WA USA. RP Mullins, JI (reprint author), Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. EM jmullins@u.washington.edu OI Brander, Christian/0000-0002-0548-5778 FU Boeing Corporation; NIH [AI57005]; University of Washington Center for AIDS Research [AI27757] FX This work was supported by a gift from the Boeing Corporation, and by grants from the NIH to JIM (AI57005) and from the University of Washington Center for AIDS Research (AI27757). The funding agencies had no role in the study. NR 58 TC 12 Z9 14 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 5 PY 2007 VL 2 IS 9 AR e823 DI 10.1371/journal.pone.0000823 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10HQ UT WOS:000207455500007 PM 17786195 ER PT J AU Hepner, KA Rowe, M Rost, K Hickey, SC Sherbourne, CD Ford, DE Meredith, LS Rubenstein, LV AF Hepner, Kimberly A. Rowe, Melissa Rost, Kathryn Hickey, Scot C. Sherbourne, Cathy D. Ford, Daniel E. Meredith, Lisa S. Rubenstein, Lisa V. TI The effect of adherence to practice guidelines on depression outcomes SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; DISSEMINATING QUALITY IMPROVEMENT; PROSPECTIVE PAYMENT SYSTEM; PRIMARY-CARE PRACTICE; COLLABORATIVE CARE; STANDARDIZED PATIENTS; MAJOR DEPRESSION; HEALTH-CARE; MANAGEMENT; PHYSICIANS AB Background: Few studies have assessed clinician adherence to depression practice guidelines and the relationship between clinician adherence and depression outcomes. Objective: To estimate how frequently specific guideline recommendations are followed and to assess whether following guideline recommendations is linked to improved depression outcomes. Design: Observational analysis of data collected from 1996 to 1998 in 3 randomized clinical trials. Setting: 45 primary care practices in 13 U.S. states. Patients: 1131 primary care patients with depression. Measurements: Expert panel methods were used to develop a patient survey-based index that measured adherence to clinical practice guidelines on depression. Rates of adherence to the 20 indicators that form the index were evaluated. Multivariable regression that controlled for case mix was used to assess how index scores predicted continuous and dichotomous depression measures at 12, 18, and 24 months. Results: Quality of care was high (clinician adherence >= 79%) for 6 indicators, including primary care clinician detection of depression. Quality of care was low (adherence, 20% to 38%) for 8 indicators, including management of suicide risk (3 indicators), alcohol abuse (2 indicators), and elderly patients; assessment of symptoms and history of depression; and treatment adjustment for patients who did not respond to initial treatment. Greater adherence to practice guidelines significantly predicted fewer depressive symptoms on continuous measures (P < 0.001 for 12 months, P < 0.01 for 18 months, and P < 0.001 for 24 months) and dichotomous measures (P < 0.05 for 18 and 24 months). Limitations: Data are based on patient self-report. Possible changes in practice since 1998 may limit the generalizability of the findings. Conclusions: Adherence to guidelines was high for one third of the recommendations that were measured but was very low for nearly half of the measures, pointing to specific needs for quality improvement. Guideline-concordant depression care appears to be linked to improved outcomes in primary care patients with depression. C1 RAND Corp, Hlth Program, Santa Monica, CA 90407 USA. Florida State Univ, Tallahassee, FL 32306 USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Hepner, KA (reprint author), RAND Corp, Hlth Program, 1776 Main St, Santa Monica, CA 90407 USA. EM hepner@rand.org FU AHRQ HHS [R01-HS08349]; NIMH NIH HHS [MH 63651, P50MH54623, R01 MH54444, R01MH64658] NR 50 TC 68 Z9 69 U1 1 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 4 PY 2007 VL 147 IS 5 BP 320 EP 329 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 207ZO UT WOS:000249289800005 PM 17785487 ER PT J AU Grippi, MA Mulrow, C AF Grippi, Michael A. Mulrow, Cynthia TI Trials that matter: Minimizing treatment of mild, persistent asthma SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 Amer Coll Physicians, Customer Serv, Philadelphia, PA 19106 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Grippi, MA (reprint author), Amer Coll Physicians, Customer Serv, 190 N Independence Mall W, Philadelphia, PA 19106 USA. NR 7 TC 1 Z9 1 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 4 PY 2007 VL 147 IS 5 BP 344 EP 345 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 207ZO UT WOS:000249289800009 PM 17785491 ER PT J AU Pape, LA Tsai, TT Isselbacher, EM Oh, JK O'Gara, PT Evangelista, A Fattori, R Meinhardt, G Trimarchi, S Bossone, E Suzuki, T Cooper, JV Froehlich, JB Nienaber, CA Eagle, KA AF Pape, Linda A. Tsai, Thomas T. Isselbacher, Eric M. Oh, Jae K. O'Gara, Patrick T. Evangelista, Arturo Fattori, Rossella Meinhardt, Gabriel Trimarchi, Santi Bossone, Eduardo Suzuki, Toru Cooper, Jeanna V. Froehlich, James B. Nienaber, Christoph A. Eagle, Kim A. CA IRAD Investigators TI Aortic diameter >= 5.5 cm is not a good predictor of type A aortic dissection - Observations from the international registry of acute aortic dissection (IRAD) SO CIRCULATION LA English DT Article DE aneurysm; aorta; aortic aneurysm; diagnosis ID MARFANS-SYNDROME; ASCENDING AORTA; ANEURYSMS; ROOT; DISEASE; LOCUS; VALVE; RISK; IDENTIFICATION; COMPLICATIONS AB Background-Studies of aortic aneurysm patients have shown that the risk of rupture increases with aortic size. However, few studies of acute aortic dissection patients and aortic size exist. We used data from our registry of acute aortic dissection patients to better understand the relationship between aortic diameter and type A dissection. Methods and Results-We examined 591 type A dissection patients enrolled in the International Registry of Acute Aortic Dissection between 1996 and 2005 ( mean age, 60.8 years). Maximum aortic diameters averaged 5.3 cm; 349 ( 59%) patients had aortic diameters < 5.5 cm and 229 (40%) patients had aortic diameters < 5.0 cm. Independent predictors of dissection at smaller diameters (< 5.5 cm) included a history of hypertension (odds ratio, 2.17; 95% confidence interval, 1.03 to 4.57; P=0.04), radiating pain ( odds ratio, 2.08; 95% confidence interval, 1.08 to 4.0; P=0.03), and increasing age ( odds ratio, 1.03; 95% confidence interval, 1.00 to 1.05; P=0.03). Marfan syndrome patients were more likely to dissect at larger diameters (odds ratio, 14.3; 95% confidence interval, 2.7 to 100; P=0.002). Mortality (27% of patients) was not related to aortic size. Conclusions-The majority of patients with acute type A acute aortic dissection present with aortic diameters < 5.5 cm and thus do not fall within current guidelines for elective aneurysm surgery. Methods other than size measurement of the ascending aorta are needed to identify patients at risk for dissection. C1 Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Hosp Gen Univ Valle Hebron, Barcelona, Spain. Univ Hosp S Orsola, Bologna, Italy. Robert Bosch Krankenhaus, Stuttgart, Germany. Ist Policlin San Donato, San Donato Milanese, Italy. CNR, Lecce, Italy. Univ Tokyo, Tokyo, Japan. Univ Hosp Rostock, Rostock, Germany. RP Pape, LA (reprint author), Univ Massachusetts, Sch Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM linda.pape@umassmed.edu RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 NR 30 TC 198 Z9 205 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 4 PY 2007 VL 116 IS 10 BP 1120 EP 1127 DI 10.1161/CIRCULATIONAHA.107.702720 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 207FZ UT WOS:000249238300004 PM 17709637 ER PT J AU Newton-Cheh, C Guo, CY Larson, MG Musone, SL Surti, A Camargo, AL Drake, JA Benjamin, EJ Levy, D D'Agostino, RB Hirschhorn, JN O'Donnell, CJ AF Newton-Cheh, Christopher Guo, Chao-Yu Larson, Martin G. Musone, Stacy L. Surti, Aarti Camargo, Amy L. Drake, Jared A. Benjamin, Emelia J. Levy, Daniel D'Agostino, Ralph B. Hirschhorn, Joel N. O'Donnell, Christopher J. TI Common genetic variation in KCNH2 is associated with QT interval duration - The framingham heart study SO CIRCULATION LA English DT Article; Proceedings Paper CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent, Natl Heart, Lung & Blood Inst, Amer Heart Assoc, Council Nutr, Phys Activ & Metab DE arrhythmia; electrocardiography; genetics; ion channels; long-QT syndrome ID SUDDEN CARDIAC DEATH; EXONIC SPLICING ENHANCERS; FUNCTIONAL-CHARACTERIZATION; CARDIOVASCULAR MORTALITY; HEALTHY POPULATION; RISK-FACTOR; PROLONGATION; DISEASE; HERG; POLYMORPHISM AB Background-QT prolongation is associated with increased risk of sudden cardiac death in the general population and in people exposed to QT-prolonging drugs. Mutations in the KCNH2 gene encoding the HERG potassium channel cause 30% of long-QT syndrome, and binding to this channel leads to drug-induced QT prolongation. We tested common KCNH2 variants for association with continuous QT interval duration. Methods and Results-We selected 17 single nucleotide polymorphisms and rs1805123, a previously associated missense single nucleotide polymorphism, for genotyping in 1730 unrelated men and women from the Framingham Heart Study. rs3807375 genotypes were associated with continuous QT interval duration in men and women (2-df P=0.002), with a dominant model suggested (P=0.0004). An independent sample of 871 Framingham Heart Study men and women replicated the association (1-sided dominant P=0.02). On combined analysis of 2123 subjects, individuals with AA or AG genotypes had a 0.14-SD (SE, 0.04) or 3.9-ms higher age-, sex- and RR-adjusted QT interval compared with GG individuals (P=0.00006). The previously reported association of rs1805123 (K897T) replicated under a dominant (AA/AC, 0.06 SD [SE, 0.07] or 3.1 ms higher versus CC; 1-sided P=0.04) or additive model (0.06 SD [SE, 0.03] or 1.6 ms higher per A allele; 1-sided P=0.01). Conclusions-Two common genetic variants at the KCNH2 locus are associated with continuous QT interval duration in an unselected community-based sample. Studies to determine the influence of these variants on risk of sudden cardiac death and drug-induced arrhythmias should be considered. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. MIT, Cambridge, MA 02139 USA. Broad Inst Harvard, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,GRB847, Boston, MA 02114 USA. EM cnewtoncheh@partners.org; odonnellc@nhlbi.nih.gov OI Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL66582, K23HL080025, N01-HC-25195, T32HL07575] NR 54 TC 58 Z9 58 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 4 PY 2007 VL 116 IS 10 BP 1128 EP 1136 DI 10.1161/CIRCULATIONAHA.107.710780 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 207FZ UT WOS:000249238300005 PM 17709632 ER PT J AU Roe, MT Chen, AY Mehta, RH Li, Y Brindis, RG Smith, SC Rumsfeld, JS Gibler, WB Ohman, EM Peterson, ED AF Roe, Matthew T. Chen, Anita Y. Mehta, Rajendra H. Li, Yun Brindis, Ralph G. Smith, Sidney C., Jr. Rumsfeld, John S. Gibler, W. Brian Ohman, E. Magnus Peterson, Eric D. TI Influence of inpatient service specialty on care processes and outcomes for patients with non-ST-segment elevation acute coronary syndromes SO CIRCULATION LA English DT Article DE coronary disease; patients; patient care; medical specialties; guidelines ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; PHYSICIAN SPECIALTY; AMERICAN-COLLEGE; ELDERLY-PATIENTS; UNSTABLE ANGINA; MANAGEMENT; CARDIOLOGISTS AB Background-Since the broad dissemination of practice guidelines, the association of specialty care with the treatment of patients with acute coronary syndromes has not been studied. Methods and Results-We evaluated 55 994 patients with non -ST-segment elevation acute coronary syndromes ( ischemic ST-segment changes and/or positive cardiac markers) included in the CRUSADE ( Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Quality Improvement Initiative from January 2001 through September 2003 at 301 tertiary US hospitals with full revascularization capabilities. We compared baseline characteristics, the use of American College of Cardiology/American Heart Association guidelines class I recommendations, and in-hospital outcomes by the specialty of the primary in-patient service ( cardiology versus noncardiology). A total of 35 374 patients (63.2%) were primarily cared for by a cardiology service, and these patients had lower-risk clinical characteristics, but they more commonly received acute (<= 24 hours) medications, invasive cardiac procedures, and discharge medications and lifestyle interventions. Acute care processes were improved when care was provided by a cardiology service regardless of the propensity to receive cardiology care. The adjusted risk of in-hospital mortality was lower with care provided by a cardiology service ( adjusted odds ratio 0.80, 95% confidence interval 0.73 to 0.88), and adjustment for differences in the use of acute medications and invasive procedures partially attenuated this mortality difference ( adjusted odds ratio 0.92, 95% confidence interval 0.83 to 1.02). Conclusions-Non-ST-segment elevation acute coronary syndrome patients primarily cared for by a cardiology inpatient service more commonly received evidence-based treatments and had a lower risk of mortality, but these patients had lower-risk clinical characteristics. Results from the present analysis highlight the difficulties with accurately determining how specialty care is associated with treatment patterns and clinical outcomes for patients with acute coronary syndromes. Novel methodologies for evaluating the influence of specialty care for these patients need to be developed and applied to future studies. C1 Duke Clin Res Inst, Durham, NC 27705 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. San Francisco Med Ctr, San Francisco, CA USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. RP Roe, MT (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM matthew.roe@duke.edu NR 18 TC 29 Z9 29 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 4 PY 2007 VL 116 IS 10 BP 1153 EP 1161 DI 10.1161/CIRCULATIONAHA.107.697003 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 207FZ UT WOS:000249238300008 PM 17709638 ER PT J AU London, B Albert, C Anderson, ME Giles, WR Van Wagoner, DR Balk, E Billman, GE Chung, M Lands, W Leaf, A McAnulty, J Martens, JR Costello, RB Lathrop, DA AF London, Barry Albert, Christine Anderson, Mark E. Giles, Wayne R. Van Wagoner, David R. Balk, Ethan Billman, George E. Chung, Mei Lands, William Leaf, Alexander McAnulty, John Martens, Jeffrey R. Costello, Rebecca B. Lathrop, David A. TI Omega-3 fatty acids and cardiac arrhythmias: Prior studies and recommendations for future research - A report from the national heart, lung, and blood institute and office of dietary supplements omega-3 fatty acids and their role in cardiac arrhythmogenesis workshop SO CIRCULATION LA English DT Review DE arrhythmia; death; sudden; diet; electrophysiology; fatty acids ID POLYUNSATURATED FATTY-ACIDS; ALPHA-LINOLENIC ACID; RAT VENTRICULAR MYOCYTES; SARCOPLASMIC-RETICULUM FUNCTION; RANDOMIZED CONTROLLED-TRIAL; ACTION-POTENTIAL DURATION; FISH-OIL SUPPLEMENTATION; SODIUM-CHANNEL BLOCKADE; ADULT GUINEA-PIG; NF-KAPPA-B C1 Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15213 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Iowa, Dept Med, Iowa City, IA 52242 USA. Univ Calgary, Dept Kinesiol, Calgary, AB, Canada. Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Tufts Univ, New England Med Ctr, Dept Med, Boston, MA 02111 USA. Ohio State Univ, Dept Physiol & Cell Biol, College Pk, MD USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Good Samaritan Hosp, Portland, OR 97210 USA. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP London, B (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Scaife S-572,200 Lothrop St, Pittsburgh, PA 15213 USA. EM londonb@upmc.edu RI LATHROP, David/A-2758-2008; Van Wagoner, David/C-6783-2008; Billman, George/E-2758-2011 OI Van Wagoner, David/0000-0001-8250-9828; NR 167 TC 108 Z9 109 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 4 PY 2007 VL 116 IS 10 BP E320 EP E335 DI 10.1161/CIRCULATIONAHA.107.712984 PG 16 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 207FZ UT WOS:000249238300015 PM 17768297 ER PT J AU Cheruvu, PK Finn, AV Gardner, C Caplan, J Goldstein, J Stone, GW Virmani, R Muller, JE AF Cheruvu, Pavan K. Finn, Aloke V. Gardner, Craig Caplan, Jay Goldstein, James Stone, Gregg W. Virmani, Renu Muller, James E. TI Frequency and distribution of thin-cap fibroatheroma and ruptured plaques in human coronary arteries: A Pathologic study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ATHEROSCLEROTIC PLAQUE; INTRAVASCULAR ULTRASOUND; VULNERABLE PLAQUE; UNSTABLE ANGINA; IN-VIVO; INFLAMMATION; MULTIPLE; LESIONS; INSTABILITY AB Our purpose was to quantify the frequency and distribution of suspected vulnerable lesions, defined as thin-capped fibroatheroma (TCFA) and ruptured plaque, in human coronary artery autopsy specimens. Background Most acute coronary events and sudden death are believed to arise from rupture of a TCFA followed by thrombosis. Although there is general agreement that clinical events are usually caused by focal lesions, there is considerable debate over the relative importance of focal versus systemic factors in the pathogenesis of atherosclerosis. Methods We longitudinally sectioned coronary arteries from 50 whole hearts taken from patients (mean age 73 years 64% men) dying of cardiovascular (n = 33), noncardiovascular (n = 13), and unknown (n = 4) causes. A total of 3,639 longitudinal segments of length 3 mm were sectioned from 148 arteries, accounting for 10.9 m of total tissue length. Specimens were classified on the basis of histology and computer-aided morphometry. Results Twenty-three TCFA and 19 ruptured plaques were found (mean +/- SD: 0.46 +/- 0.95 and 0.38 +/- 0.70 per heart, respectively), and these lesions accounted for only 1.6% and 1.2%, respectively, of the total length of the coronary tree examined in patients dying of cardiovascular causes. The majority of TCFA and ruptured plaque localized in the proximal third of the major coronary arteries, and in 92% of cases these lesions clustered within 2 or fewer nonoverlapping 20-mm segments. Conclusions The suspected precursors of rupture-mediated thrombosis occur in a limited, focal distribution in the coronary arteries. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. InfraReDx Inc, Burlington, MA USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Columbia Univ, Med Ctr, New York, NY USA. Cardiovasc Res Fdn, New York, NY USA. CV Path, Gaithersburg, MD USA. RP Cheruvu, PK (reprint author), 104 Toxteth St,4 Brookline, Brookline, MA 02446 USA. EM pavan_cheruvu@hms.harvard.edu NR 51 TC 199 Z9 205 U1 1 U2 8 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 4 PY 2007 VL 50 IS 10 BP 940 EP 949 DI 10.1016/j.jacc.2007.04.086 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 207MH UT WOS:000249254700004 PM 17765120 ER PT J AU Nasir, K Shaw, LJ Liu, ST Weinstein, SR Mosler, TR Flores, PR Flores, FR Raggi, P Berman, DS Blumenthal, RS Budoff, MJ AF Nasir, Khurrarn Shaw, Leslee J. Liu, Sandy T. Weinstein, Steven R. Mosler, Tristen R. Flores, Phillip R. Flores, Ferdinand R. Raggi, Paolo Berman, Daniel S. Blumenthal, Roger S. Budoff, Matthew J. TI Ethnic differences in the prognostic value of coronary artery calcification for all-cause mortality SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; ELECTRON-BEAM TOMOGRAPHY; RISK-FACTORS; HEART-DISEASE; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS MESA; COMPUTED-TOMOGRAPHY; RACIAL-DIFFERENCES; CALCIUM PREVALENCE; GENDER AB The purpose of this study was to evaluate the prognostic value of coronary artery calcium (CAC), a known marker of subclinical atherosclerosis, in a large, ethnically diverse cohort of 14,812 patients for the prediction of all-cause mortality. Background Disparities in case fatality rates for heart disease among ethnic groups are well known. In 2001, rates of death from heart disease were 30% higher among African Americans (AA) than non-Hispanic whites (NHW). Some of this variability may be due to differing pathophysiological mechanisms and effects of underlying atherosclerosis. Methods Ten-year death rates from all causes (total deaths = 505) were compared using risk-adjusted Cox proportional hazards models in AA (n = 637), Hispanic (HIS, n = 1,334), Asian (AS, n = 1,065), and NHW (n = 11,776) populations. Results Ethnic minority patients were generally younger (0.3 to 4 years), more often persons with diabetes (p < 0.0001), hypertensive (p < 0.0001), and female (p < 0.0001). The prevalence of CAC scores :100 was highest in NHW (31%) and lowest for HS (18%) (p < 0.0001). Overall survival was 96%, 93%, and 92% for AS, NHW, and HS, respectively, as compared with 83% for AA (p < 0.0001). When comparing prognosis by CAC scores in ethnic minorities as compared with NHW, relative risk ratios were highest for AA with CAC scores :400 exceeding 16.1 (p < 0.0001). Hispanics with CAC scores 400 had relative risk ratios from 7.9 to 9.0, whereas AS with CAC scores >= 1,000 had relative risk ratios 6.6-fold higher than NHW (p < 0.0001). Conclusions Consistent with population evidence, AA with increasing burden of subclinical coronary artery disease were the highest-risk ethnic minority population. These data support a growing body of evidence noting substantial differences in cardiovascular risk by ethnicity. C1 Harbor UCLA Res & Educ Inst, Div Cardiol, Torrance, CA 90502 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MRI PET CT Program, Boston, MA USA. Emory Univ, Dept Med, Div Cardiol, Atlanta, GA 30322 USA. Cedars Sinai Med Ctr, Dept Imaging & Med, Los Angeles, CA 90048 USA. Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. RP Nasir, K (reprint author), Harbor UCLA Res & Educ Inst, Div Cardiol, 1124 W Carson St,RB2, Torrance, CA 90502 USA. EM Budof@ucla.edu NR 34 TC 87 Z9 92 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 4 PY 2007 VL 50 IS 10 BP 953 EP 960 DI 10.1016/j.jacc.2007.03.066 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 207MH UT WOS:000249254700006 PM 17765122 ER PT J AU Furie, KL Smith, EE AF Furie, Karen L. Smith, Eric E. TI Metabolic syndrome: A target for preventing leukoaraiosis and age-related dementia? SO NEUROLOGY LA English DT Editorial Material ID WHITE-MATTER LESIONS; ALZHEIMER-DISEASE; RISK-FACTORS; STROKE; MEN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Smith, EE (reprint author), Ctr Stroke Res, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM EESmith@partners.org OI Smith, Eric/0000-0003-3956-1668 NR 13 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 4 PY 2007 VL 69 IS 10 BP 951 EP 952 DI 10.1212/01.wnl.0000271094.43789.0e PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 207FX UT WOS:000249238100002 PM 17785662 ER PT J AU Varma, H Cheng, R Voisine, C Hart, AC Stockwell, BR AF Varma, Hemant Cheng, Richard Voisine, Cindy Hart, Anne C. Stockwell, Brent R. TI Inhibitors of metabolism rescue cell death in Huntington's disease models SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE caspase; ERK; survival signaling; drugs; neurodegeneration ID MUTANT HUNTINGTIN; SODIUM-FLUORIDE; MITOCHONDRIAL-FUNCTION; DIETARY RESTRICTION; SURVIVAL PATHWAYS; TRANSGENIC MICE; DEGENERATION; DYSFUNCTION; APOPTOSIS; TOXICITY AB Huntington's disease (HD) is a fatal inherited neurodegenerative disorder. HD is caused by polyglutamine expansions in the huntingtin (htt) protein that result in neuronal loss and contribute to HID pathology. The mechanisms of neuronal loss in HD are elusive, and there is no therapy to alleviate HD. To find small molecules that slow neuronal loss in HD, we screened 1,040 biologically active molecules to identify suppressors of cell death in a neuronal cell culture model of HID. We found that inhibitors of mitochondrial function or glycolysis rescued cell death in this cell culture and in in vivo HID models. These inhibitors prevented cell death by activating prosurvival ERK and AKT signaling but without altering cellular ATIP levels. ERK and AKT inhibition through the use of specific chemical inhibitors abrogated the rescue, whereas their activation through the use of growth factors rescued cell death, suggesting that this activation could explain the protective effect of metabolic inhibitors. Both ERK and AKT signaling are disrupted in HD, and activating these pathways is protective in several HD models. Our results reveal a mechanism for activating prosurvival signaling that could be exploited for treating HID and possibly other neurodegenerative disorders. C1 Columbia Univ, Dept Biol Sci, Fairchild Ctr, New York, NY 10027 USA. Columbia Univ, Dept Chem, Fairchild Ctr, New York, NY 10027 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Boston, MA 02129 USA. RP Stockwell, BR (reprint author), Columbia Univ, Dept Biol Sci, Fairchild Ctr, MC 2406,1212 Amsterdam Ave, New York, NY 10027 USA. EM stockwell@biology.columbia.edu OI Cheng, Richard/0000-0003-2552-6773 NR 55 TC 33 Z9 34 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 4 PY 2007 VL 104 IS 36 BP 14525 EP 14530 DI 10.1073/pnas.0704482104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 208QF UT WOS:000249333600062 PM 17726098 ER PT J AU Wong, J Mathis, D Benoist, C AF Wong, Jamie Mathis, Diane Benoist, Christophe TI TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; REG CELLS; MICE; EXPRESSION; REPERTOIRES; SPECIFICITY; RECEPTORS; INDUCTION; ORIGIN AB Foxp3-expressing regulatory T ( T reg) cells derive primarily from selection in the thymus. Yet conversion of mature conventional CD4(+) T ( T conv) cell lymphocytes can be achieved in Several conditions, such as transforming growth factor beta treatment, homeostatic expansion, or chronic exposure to low-dose antigen. Such conversion might provide a means to generate peripheral tolerance by " converting " potentially damaging T cells that react to self-antigens. We tested this hypothesis in mice transgenic for the BDC2.5 T cell receptor ( TCR), which is representative of a diabetogenic specificity that is naturally present in NOD mice and reactive against a pancreatic self-antigen. In the thymus, before any exposure to antigen, clonotype-positive T reg and T conv cells express a second TCR alpha chain derived from endogenous loci. High-throughput single-cell sequencing of secondary TCRs of the V alpha 2 family showed their joining CDR3 alpha regions to be very different in T reg and T conv cell thymocytes. These specific CDR3 alpha motifs, thus, provided a " tag " with which to test the actual impact of T conv to T reg cell conversion in response to peripheral self-antigen; should the autoreactive clonotypic TCR induce T conv to T reg cell conversion upon encounter of cognate antigen in the pancreas or draining lymph node, one would expect to detect tag CDR3 alpha motifs from T conv cells in the T reg cell populations. Sequencing large numbers of peripheral BDC+ V alpha 2(+) cells showed that little to no conversion occurs in response to this pancreatic autoantigen. C1 Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Mathis, D (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM dm@joslin.harvard.edu; cb@joslin.harvard.edu FU NIAID NIH HHS [R01 AI 51530, R01 AI051530] NR 30 TC 61 Z9 62 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 3 PY 2007 VL 204 IS 9 BP 2039 EP 2045 DI 10.1084/jem.20070822 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 207AW UT WOS:000249225000005 PM 17724131 ER PT J AU Budoff, MJ Katz, R Wong, ND Nasir, K Mao, SS Takasu, J Kronmal, R Detrano, RC Shavelle, DM Blumenthal, RS O'Brien, KD Carr, JJ AF Budoff, Matthew J. Katz, Ronit Wong, Nathan D. Nasir, Khurram Mao, Song Shou Takasu, Junichiro Kronmal, Richard Detrano, Robert C. Shavelle, David M. Blumenthal, Roger S. O'Brien, Kevin D. Carr, J. Jeffrey TI Effect of scanner type on the reproducibility of extracoronary measures of calcification: The multi-ethnic study of atherosclerosis SO ACADEMIC RADIOLOGY LA English DT Article DE coronary calcium; computed tomography; coronary heart disease; atherosclerosis; reproducibility ID BEAM COMPUTED-TOMOGRAPHY; CORONARY-ARTERY-DISEASE; AORTIC-VALVE CALCIUM; MITRAL ANNULUS; CT; ASSOCIATION; QUANTIFICATION; MARKER; MESA AB Rationale and Objectives. Cardiac computed tomography (CT) has been used extensively to measure coronary artery calcification. However. extracoronary calcifications, such as aortic valve calcification (AVC), may have independent clinical significance as well. The ability to track calcification is dependent on the reproducibility of the original measurement, and the variability of extracoronary calcification measurements still is unknown. Accurate quantification of calcification of the aortic valve. mitral annulus (MAC), and thoracic aortic (TAC) may be possible by using cardiac CT. Methods. A total of 1,729 randomly chosen participants (ages 45-84, 53% female, 28% African-American, 36% Caucasian, 11% Chinese, 25% Hispanic) of the Multi-Ethnic Study of Atherosclerosis underwent dual scanning by electron beam CT (EBT) or multidetector CT (MDCT) to assess coronary and extra-coronary calcifications. Two calcium measuremerit mwethods-Agatston score (AS) and volume score (VS)-were measured for each scan. Concordance for calcium C positivity was assessed among all scans. Mean absolute and relative differences between calcium measures on scans I and 2, excluding cases for which both scans had a measure of zero, was modeled by using linear regression to compare variability between scanner types. A repeated measures analysis of variance test was used to compare variability across calcium measures, with mean percentage absolute difference as the Outcome measure. Results. Concordances for the presence of calcium between duplicate scans were high and similar for both EBT and MDCT. Concordance was high for all three extracoronary measures, with a kappa statistic Of kappa = 0.94-0.96. For all three extracoronary sites. Bland-Altman plots demonstrated excellent agreement, with almost all measures failing within the boundaries of the 95% confidence limits of reproducibility. AVC interscan variability was approximately 8% for both AS and VS, with improved variability for EBT as compared with MDCT. Mitral annular calcification demonstrated slightly lower variability than AVC for both scanner types (approximately 6%), with no significant differences between MDCT and EBT. Of the three extracoronary sites, TAC had the highest variability (10%), with MDCT variability slightly lower than EBT variability (9.3 vs. 10.2%, respectively, P = NS). Agatson and volume scores for each of the three extracoronary sites were similar. Conclusions. Overall rescan measurement variabilities for extracoronary calcification are low and should not be an impediment to the use of this test for studying progression of extracoronary calcification over time. C1 Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Div Cardiol, Torrance, CA 90502 USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif Irvine, Div Cardiol, Irvine, CA 92717 USA. Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. Wake Forest Sch Med, Dept Radiol, Wake Forest, NC USA. RP Budoff, MJ (reprint author), Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Div Cardiol, 1124 W Carson St,RB2, Torrance, CA 90502 USA. EM Budoff@ucla.edu RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 FU NHLBI NIH HHS [N01-HC-95165, N01-HC-95159, N01-HC-95169, R01-HL-63963-01A1] NR 19 TC 31 Z9 31 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2007 VL 14 IS 9 BP 1043 EP 1049 DI 10.1016/j.acra.2007.05.021 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 205RX UT WOS:000249133400006 PM 17707311 ER PT J AU Kim, HS Park, JS Park, JY Hong, SR Seong, SJ Kim, HS Wilbur, DC AF Kim, Hye Sun Park, Jong Sook Park, Ji Young Hong, Sung Ran Seong, Seok Ju Kim, Hy Sook Wilbur, David C. TI Comparison of two preparation methods for endocervical evaluation SO ACTA CYTOLOGICA LA English DT Article DE cervical smears; endocervical brush cytology; SurePath ID THIN-LAYER PREPARATIONS; CONVENTIONAL PAP-SMEARS; AUTOCYTE PREP; CYTOLOGY; CURETTAGE; BRUSH; PERFORMANCE; CYTOBRUSH; IMPACT AB Objective To assess the validity of SurePath liquid-hased preparation method for examination of endocervical brush specimens as a substitute for conventionally prepared cytology methods for evaluating the endocervical canal during colposcopic examination and biopsy. Study Design Paired SurePath liquid-based test slides and conventional smears were obtained using an endocervical brush in a split sample protocol before biopsy at the time of colposcopy. The level of agreement between cytologic results obtained was assessed. Accuracy and operating characteristics were evaluated compared to histologic follow-up. Results Agreement between cytology results for the methods was excellent. The overall kappa was 0.924 (p = 0.0000). There was exact agreement on interpretation between the methods in 283 of 299 cases (94.6%). Cytohistologic follow-up results correlation were: SurePath liquid-based Pap test resultsand conventional smear results agreed with histology results in 47.8% and 49.2% of cases, respectively. Allowing for a discrepancy within 1 level of severity of cytologic grade, agreements were 76.6% and 77.2%, respectively. Conclusion This study demonstrates that the SurePath method is equivalent to conventional endocervical brush cytology preparation and performs well for detection of cervical intraepithelial lesions and cancer. SurePath is acceptable for endocervical evaluation as a substitute for endocervical curettage at colposcopic biopsy. C1 Kwandong Univ, Coll Med, Cheil Gen Hosp, Dept Pathol, Seoul 100380, South Korea. Kwandong Univ, Coll Med, Womens Healthcare Ctr, Seoul 100380, South Korea. Kyungbuk Univ, Sch Med, Dept Obstet & Gynecol, Seoul, South Korea. Pochon CHA Univ, Coll Med, Kangnam CHA Gen Hosp, Dept Gynecol & Obstet, Seoul, South Korea. Kyungpook Natl Univ Hosp, Dept Pathol, Deagu, South Korea. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Kim, HS (reprint author), Kwandong Univ, Coll Med, Cheil Gen Hosp, Dept Pathol, 1-19 Mookjung Dong, Seoul 100380, South Korea. NR 21 TC 3 Z9 3 U1 0 U2 0 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 2007 VL 51 IS 5 BP 742 EP 748 DI 10.1159/000325837 PG 7 WC Pathology SC Pathology GA 212JF UT WOS:000249591900008 PM 17910344 ER PT J AU Nakashima-Yasuda, H Uryu, K Robinson, J Xie, SX Hurtig, H Duda, JE Arnold, SE Siderowf, A Grossman, M Leverenz, JB Woltjer, R Lopez, OL Hamilton, R Tsuang, DW Galasko, D Masliah, E Kaye, J Clark, CM Montine, TJ Lee, VMY Trojanowski, JQ AF Nakashima-Yasuda, Hanae Uryu, Kunihiro Robinson, John Xie, Sharon X. Hurtig, Howard Duda, John E. Arnold, Steven E. Siderowf, Andrew Grossman, Murray Leverenz, James B. Woltjer, Randy Lopez, Oscar L. Hamilton, Ronald Tsuang, Debby W. Galasko, Douglas Masliah, Eliezer Kaye, Jeffrey Clark, Christopher M. Montine, Thomas J. Lee, Virginia M. -Y. Trojanowski, John Q. TI Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases SO ACTA NEUROPATHOLOGICA LA English DT Article DE frontotemporal lobar degeneration; TDP-43; dementia with Lewy bodies; Parkinson's disease ID FRONTOTEMPORAL LOBAR DEGENERATION; AMYOTROPHIC-LATERAL-SCLEROSIS; NUCLEAR FACTOR TDP-43; ALPHA-SYNUCLEIN; NEURODEGENERATIVE DISEASES; UBIQUITIN PATHOLOGY; DEMENTIA; TAU; INCLUSIONS; GENE AB Here, we investigated if TAR-DNA-binding protein-43 (TDP-43), the disease protein-in frontotemporal lobar degeneration and ubiquitin inclusions with or without motor neuron disease as well as amyotrophic lateral sclerosis, also formed inclusions in Lewy body (LB) disorders including Parkinson's disease (PD) without or with dementia (PDD), and dementia with LBs (DLB) alone or in association with Alzheimer's disease (AD). Immunohistochemical analyses of TDP-43 in clinically well characterized and pathologically confirmed cases of DLB + AD, PD and PDD demonstrated TDP-43 pathology in the following percentage of cases: DLB + AD = 25/80 (31.3%); PD = 5/69 (7.2%); PDD 4/21 (19%), while DLB and normal controls exhibited Do (0/10, 0%) and one cases (1/33, 3%) presenting TDP-43 pathology, respectively. Significant differences in the prevalence of TDP-43 lesions were noted between disease versus normal brains (P < 0.001) as well as demented versus non-demented brains (P < 0.001). Statistical analyses revealed a positive relationship between TDP-43 lesions and several clinical and pathological parameters in these disorders suggesting the TDP-43 pathology may have co-morbid effects in LB diseases. This study expands the concept of TDP-43 proteinopathies by implicating TDP-43 lesions in mechanisms of neurodegeneration in LB disorders. C1 Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VAMC, Parkinsons Dis Res, Educ & Clin Ctr, Philadelphia, PA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Mental Illness Res, Educ & Clin Ctr, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Parkinsons Dis Res, Educ & Clin Ctr, Seattle, WA USA. RP Trojanowski, JQ (reprint author), Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, HUP-Maloney 3rd Floor, Philadelphia, PA 19104 USA. EM trojanow@mail.med.upenn.edu RI Arnold, Steven/J-7546-2012; Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AG-09215, AG-17586, P01 AG009215, P01 AG017586, AG-10124] NR 31 TC 196 Z9 199 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD SEP PY 2007 VL 114 IS 3 BP 221 EP 229 DI 10.1007/s00401-007-0261-2 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 205XT UT WOS:000249149200003 PM 17653732 ER PT J AU Schuller, U Heine, V Mao, J Kho, AT Dillon, AK Han, YG Sun, T Qian, Y Ma, Q Alvarez-Buylla, A McMahon, AP Rowitch, DH Ligon, KL AF Schueller, U. Heine, V. Mao, J. Kho, A. T. Dillon, A. K. Han, Y.-G. Sun, T. Qian, Y. Ma, Q. Alvarez-Buylla, A. McMahon, A. P. Rowitch, D. H. Ligon, K. L. TI Developmental origins of medulloblastoma from regionally restricted multipotent progenitors in the mammalian central nervous system SO ACTA NEUROPATHOLOGICA LA English DT Meeting Abstract CT Joint Meeting of the German-Society-of-Neuropathology-and-Neuroanatomy (DGNN)/Polish-Associatin-of-Neuropathologists CY SEP 05-08, 2007 CL Greifswald, GERMANY SP German Soc Neruopathol & Neuroanat, Polish Assoc Neuropathologists C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Inst Regenerat Med, San Francisco, CA USA. Dept Neurolog Surg, San Francisco, CA USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Univ Munich, Ctr Neuropathol, Munich, Germany. Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA. RI Heine, Vivi/F-1741-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD SEP PY 2007 VL 114 IS 3 MA 62 BP 326 EP 326 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 205XT UT WOS:000249149200081 ER PT J AU Morgenstern, J McKay, JR AF Morgenstern, Jon McKay, James R. TI Rethinking the paradigms that inform behavioral treatment research for substance use disorders SO ADDICTION LA English DT Review DE behavioral treatments; mechanisms of change; substance use disorders; treatment process ID COCAINE-DEPENDENT PATIENTS; MARIJUANA TREATMENT PROJECT; INTERACTIONAL GROUP-THERAPY; ALCOHOL-USE DISORDERS; DRUG-USE DISORDERS; RELAPSE PREVENTION; COPING-SKILLS; OUTPATIENT TREATMENT; BRIEF INTERVENTIONS; RANDOMIZED-TRIAL AB Aim Over the last three decades, the randomized controlled trial or 'psychotherapy technology' approach has been the dominant model of inquiry in research on addiction treatment. This period has yielded impressive discoveries, but recent failures to confirm core research hypotheses such as occurred in Project MATCH and the Cocaine Collaborative Treatment Study have raised questions about future research directions. The paper identifies several testable assumptions of the psychotherapy technology model. A review is conducted on four substance use disorder behavioral interventions-motivational interviewing, cognitive-behavioral treatment, behavioral couples treatment and 12-Step-oriented treatment-to determine whether these assumptions are supported by research findings. Results Overall, the review suggests weak support for the technology model of psychotherapy research. Lack of support is interpreted as indicating flaws in several model assumptions about how to conceptualize and measure patient responsivity and the interaction of non-specific and specific therapeutic factors. The paper offers alternative strategies for addressing these issues drawn from the general psychotherapy process literature and provides illustrative examples of how these could be used to spur innovation in addiction treatment research. The addiction treatment research field is coming up against the limitations of the psychotherapy technology model as the dominant paradigm guiding treatment research. It is important for addiction treatment researchers to explore alternative conceptualizations and methodologies in order to understand more clearly how treatment works. C1 Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Morgenstern, J (reprint author), Substance Abuse Serv, Dept Psychiat, 180 Ft Washington Ave,HP 236, New York, NY 10032 USA. EM jm977@columbia.edu FU NIAAA NIH HHS [1R01 AA13873, R01 AA14850]; NIDA NIH HHS [1R01 DA15971, K02 DA000361] NR 99 TC 76 Z9 77 U1 4 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD SEP PY 2007 VL 102 IS 9 BP 1377 EP 1389 DI 10.1111/j.1360-0443.2007.01882.x PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 198ZK UT WOS:000248665800012 PM 17610541 ER PT J AU Covell, NH Weissman, EM Schell, B McCorkle, BH Summerfelt, WT Weiden, PJ Essock, SM AF Covell, Nancy H. Weissman, Ellen M. Schell, Bonnie McCorkle, Brian H. Summerfelt, W. Thomas Weiden, Peter J. Essock, Susan M. TI Distress with medication side effects among persons with severe mental illness SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY JUN 01-04, 2004 CL Phoenix, AZ SP New Clin Drug Evaluat Unit, NIMH DE COSP; consumer-operated; medication; side effects; serious mental illness ID QUALITY-OF-LIFE; WEIGHT-GAIN; ANTIPSYCHOTIC MEDICATIONS; SUBJECTIVE EXPERIENCES; SCHIZOPHRENIC-PATIENTS; CLOZAPINE; DRUGS; NEUROLEPTICS; PERSPECTIVE; OBESITY AB We examined prevalence and perceived distress resulting from self-reported side effects (SEs) attributed to psychotropic medications among individuals with severe mental illness participating in a study of consumer-operated services. We examined gender and racial differences using logistic regression, conducted factor analyses of SEs, and examined correlations between distress and self-reported symptoms. Over 90% reported at least one SE, and nearly two-thirds reported a high level of distress with at least one SE. The most distressing SEs reported were embarrassment from weight gain, weight gain, dry mouth, and sedation. The likelihood of distress by particular SEs varied by gender and race. C1 Connecticut Dept Mental Hlth & Addict Serv, Div Res, Hartford, CT 06134 USA. Mt Sinai Hosp, Mt Sinai Sch Med, Div Hlth Serv Res, New York, NY 10029 USA. James J Peters Vet Affairs Med Syst, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Piedmont Behav Healthcare, Off Consumer Affairs, Concord, NC USA. Boston Univ, Albert & Jessie Danielsen Inst, Ctr Study Religion & Psychol, Boston, MA 02215 USA. Univ Chicago, Ctr Hlth & Social Sci, Chicago, IL 60637 USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Columbia Univ, Dept Mental Hlth Serv, Coll Phys & Surg, New York, NY USA. Columbia Univ, Dept Policy Res, Coll Phys & Surg, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY USA. RP Covell, NH (reprint author), Connecticut Dept Mental Hlth & Addict Serv, Div Res, 410 Capitol Ave,MS 14RSD,POB 341431, Hartford, CT 06134 USA. EM nancy.covell@po.state.ct.us FU CMHS SAMHSA HHS [SM-52367, SM-52362, SM-52355, SM-52372, SM-52352, SM-52332, SM-52328, SM-52363] NR 53 TC 6 Z9 6 U1 0 U2 0 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD SEP PY 2007 VL 34 IS 5 BP 435 EP 442 DI 10.1007/s10488-007-0131-1 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 205MG UT WOS:000249117400002 PM 17653845 ER PT J AU Covell, NH McCorkle, BH Weissman, EM Summerfelt, T Essock, SM AF Covell, Nancy H. McCorkle, Brian H. Weissman, Ellen M. Summerfelt, Tom Essock, Susan M. TI What's in a name? Terms preferred by service recipients SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE COSP; consumer-operated; client; patient; label ID MENTAL-HEALTH-SERVICES; USERS AB In a large (n = 1,827) multi-site study examining effectiveness of consumer operated service programs as an adjunct to traditional mental health services, we examined individuals' preferred term describing their status as service recipients, and we applied logistic regression to examine whether preference varied by gender, race or diagnosis. Preferred terms were client (39%), patient (22%), consumer (16%), survivor (11%), other (11%) and ex-patient (1%), varying by site. Controlling for site, preferences did not vary by gender, race, or diagnosis. The lack of consensus suggests clinicians, researchers, program administrators, and policymakers should be sensitive to individuals' preferences. C1 Connecticut Dept Mental Hlth & Addict Serv, Div Res, Hartford, CT 06134 USA. Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY USA. Boston Univ, Ctr Study Religion & Psychol, Albert & Jessie Danielsen Inst, Boston, MA 02215 USA. James J Peters Vet Affairs Med Syst, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Univ Chicago, Ctr Hlth & Social Sci, Chicago, IL 60637 USA. Columbia Univ, Dept Mental Hlth Serv & Policy Res, Dept Psychiat, Coll Phys & Surg, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY USA. RP Covell, NH (reprint author), Connecticut Dept Mental Hlth & Addict Serv, Div Res, 410 Capitol Ave,MS 14RSD,341431, Hartford, CT 06134 USA. EM nancy.covell@po.state.ct.us NR 9 TC 14 Z9 14 U1 0 U2 2 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD SEP PY 2007 VL 34 IS 5 BP 443 EP 447 DI 10.1007/s10488-007-0123-1 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 205MG UT WOS:000249117400003 PM 17464558 ER PT J AU Kaushal, R Goldmann, DA Keohane, CA Christino, M Honour, M Hale, AS Zigmont, K Soleymani, L Perrin, J Bates, DW AF Kaushal, Rainu Goldmann, Donald A. Keohane, Carol A. Christino, Melissa Honour, Melissa Hale, Andrea S. Zigmont, Katherine Soleymani, Lisa Lehmann Perrin, James Bates, David W. TI Adverse drug events in pediatric outpatients SO AMBULATORY PEDIATRICS LA English DT Article DE medication errors; patient safety ID PHYSICIAN ORDER ENTRY; MEDICATION ERRORS; HOSPITALIZED-PATIENTS; PREVENTION; CARE AB Objective.-To determine rates and types of adverse drug events (ADEs) in the pediatric ambulatory setting. Methods.-A prospective cohort study at 6 office practices in the greater Boston area was conducted over 2-month periods. Duplicate prescription review, telephone surveys 10 days and 2 months after visit, and chart reviews were done. A 2-physician panel classified the severity, preventability, and ability to ameliorate (ie, if the severity or duration of the side effect could have been mitigated by improved communication) ADEs. Results.-We identified 57 preventable ADEs (rate 3%; 95% confidence intervals [CI], 3%-4%) and 226 nonpreventable ADEs (rate 13%; 95% CI, 11%-15%) in the medical care of 1788 patients. Of the ADEs, 152 (54%) were able to be ameliorated. None of the preventable ADEs were life threatening, although 8 (14%) were serious. Forty (70%) of the preventable ADEs were related to parent drug administration. Improved communication between health care providers and parents and improved communication between pharmacists and parents, whether in the office or in the pharmacy, were judged to be the prevention strategies with greatest potential. Conclusions.-Patient harm from medication use was common in the pediatric ambulatory setting. Errors in home medication administration resulted in the majority of preventable ADEs. Approximately one fifth of ADEs were potentially preventable and many more were potentially able to be ameliorated. Rates of ADEs due to errors are comparable in children and adults despite less medication utilization in children. C1 Cornell Univ, Dept Publ Hlth, Weill Med Coll, New York, NY 10021 USA. Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Healthcare Improvement, Cambridge, MA USA. MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. Partners Healthcare Syst, Informat Syst, Boston, MA USA. RP Kaushal, R (reprint author), Cornell Univ, Dept Publ Hlth, Weill Med Coll, 411 E 69th St KB 312, New York, NY 10021 USA. EM rkaushal@partners.org FU AHRQ HHS [5 P01 HS11534-04] NR 19 TC 59 Z9 62 U1 0 U2 2 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 2007 VL 7 IS 5 BP 383 EP 389 DI 10.1016/j.ambp.2007.05.005 PG 7 WC Pediatrics SC Pediatrics GA 216RU UT WOS:000249897500008 PM 17870647 ER PT J AU Ho, PM Luther, SA Masoudi, FA Gupta, I Lowy, E Maynard, C Sales, AE Peterson, ED Fihn, SD Runisfeld, JS AF Ho, P. Michael Luther, Stacie A. Masoudi, Frederick A. Gupta, Indra Lowy, Elliott Maynard, Charles Sales, Anne E. Peterson, Eric D. Fihn, Stephan D. Runisfeld, John S. TI Inpatient and follow-up cardiology care and mortality for acute coronary syndrome patients in the Veterans Health Administration SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PHYSICIAN SPECIALTY; ELDERLY-PATIENTS; ADMITTING PHYSICIAN; OUTCOMES; PREVALENCE; THERAPY; DISEASE; DISCONTINUATION; GENERALISTS AB Background The impact of inpatient and follow-up cardiology care on patient outcomes after acute coronary syndrome (ACS) hospital discharge is unknown. Methods This was a retrospective cohort study of all patients with ACS discharged from Veterans Health Administration facilities from 2003 to 2004. Patients were stratified into 2 categories of cardiology care: (1) inpatient and follow-up cardiology care within 60 days after discharge and (2) other levels of cardiology care (inpatient only, outpatient only, and neither inpatient nor outpatient). Multivariable regression assessed the association between inpatient and follow-up cardiology care with all-cause mortality, adjusting for demographics, comorbidities, hospital presentation and treatment variables, and clustering by site. Results Of 933 patients with ACS, the majority (71.6%) had inpatient and follow-up cardiology care. Patients with inpatient and follow-up cardiology care were more likely to have prior coronary disease and diabetes and to present with myocardial infarction (vs unstable angina). All-cause mortality was lower for patients with inpatient and follow-up cardiology care (18.8% vs 22.1 %, P = .009). In multivariable analysis, patients with inpatient and follow-up cardiology care remained at lower mortality risk (hazard ratio 0.73, 95% CI 0.62-0.87) compared with patients with other levels of cardiology care. The findings were consistent when cardiology follow-up was defined as 30 or 90 days after hospital discharge. Conclusions Patients with inpatient and follow-up cardiology care have lower mortality risk after ACS. Future studies should identify mediators of this potential benefit and determine if interventions enhancing continuity of care in general, and continuity of subspecialty care in particular, after ACS will improve patient outcomes. C1 Denver VA Med Ctr, Med Serv, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80202 USA. Denver Hlth Med Ctr, Dept Med, Denver, CO USA. Puget Sound Hlth Care Syst, Hlth Serv Res, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Univ Alberta, Edmonton, AB T6G 2M7, Canada. Duke Clin Res Inst, Durham, NC USA. RP Ho, PM (reprint author), 1055 Clermont St, Denver, CO 80220 USA. EM michael.ho@uchsc.edu RI Sales, Anne/D-9678-2012; Maynard, Charles/N-3906-2015; OI Maynard, Charles/0000-0002-1644-7814; Sales, Anne/0000-0001-9360-3334 NR 30 TC 15 Z9 15 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2007 VL 154 IS 3 BP 489 EP 494 DI 10.1016/j.ohi.2007.05.018 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 209LN UT WOS:000249390100015 PM 17719295 ER PT J AU Campbell, CY Nasir, K Sarwar, A Meneghelo, RS Carvalho, JAM Blumenthal, RS Santos, RD AF Campbell, Catherine Y. Nasir, Khurram Sarwar, Ammar Meneghelo, Romeu S. Carvalho, Jose A. M. Blumenthal, Roger S. Santos, Raul D. TI Combined effect of high low-density lipoprotein cholesterol and metabolic syndrome on subclinical coronary atherosclerosis in white men without clinical evidence of myocardial ischemia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; CARDIOVASCULAR-DISEASE; ARTERY-DISEASE; HEART-DISEASE; RISK; ASSOCIATION; INFARCTION; CALCIUM; LDL; SUBFRACTIONS AB High low-density lipoprotein (LDL) cholesterol and the presence of metabolic syndrome (MS) are established risk factors for clinical and subclinical cardiovascular disease (CVD). However, the relative contribution to CVD risk of MS and high LDL cholesterol is not well defined. Therefore, the aim was assess the relative risk for the presence of coronary artery calcification (CAC) with metabolic syndrome (MS) compared with that of moderate or high LDL cholesterol. A total of 440 consecutive asymptomatic men (mean age 46 +/- 7 years, range 29 to 65) presenting for CVD risk stratification were studied. MS was defined using National Cholesterol Education Program- Adult Treatment Panel III criteria (n = 112; 24%). Moderate LDL cholesterol was defined as 130 to 159 mg/dl, and high LDL cholesterol as >= 160 mg/dl (n = 76; 17%). Overall, CAC was observed in 190 men (40%). The prevalence of CAC > 0 was lowest in MS-negative men with LDL cholesterol < 130 (35%) or 130 to 159 mg/dl (34%) and highest in MS-positive men with LDL cholesterol >= 160 mg/dl (80%). MS-positive men with LDL cholesterol of 130 to 159 mg/dl had CAC. prevalence similar to that of MS-negative men with LDL cholesterol >= 160 mg/dl (54% vs 57%, respectively). This relation persisted with additional adjustment for age, smoking status, and cholesterol-lowering medication. In logistic regression analyses, the odds ratio for CAC > 0 was highest in MS-positive men combined with high LDL cholesterol. In conclusion, these results suggest that the risk of CAC in asymptomatic men with moderate or high LDL cholesterol is magnified in persons with MS. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Sao Paulo, Med Sch Hosp, Lipid Clin Heart Inst InCor, Sao Paulo, Brazil. Albert Einstein Hosp, Prevent Med Ctr, Inst Israel Ensino & Pesquisa Albert Einstein, Philadelphia, PA 19141 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. RP Santos, RD (reprint author), Univ Sao Paulo, Med Sch Hosp, Lipid Clin Heart Inst InCor, Sao Paulo, Brazil. EM rdsf@uol.com.br RI Santos, Raul/A-1170-2010 OI Santos, Raul/0000-0002-9860-6582 NR 25 TC 9 Z9 11 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 2007 VL 100 IS 5 BP 840 EP 843 DI 10.1016/j.amjcard.2007.04.018 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 207BH UT WOS:000249226100017 PM 17719330 ER PT J AU Dunbar, NM Bankson, DD AF Dunbar, Nancy M. Bankson, Daniel D. TI Role of cardiac marker screening panels in the detection of acute myocardial infarction SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the Academy-of-Clinical-Laboratory-Physicians-and-Scientists CY JUN 07-09, 2007 CL San Diego, CA SP Acad Clin Lab Phys & Scientists C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RI Dunbar, Nancy/D-8883-2011 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 2007 VL 128 IS 3 MA 6 BP 504 EP 505 PG 2 WC Pathology SC Pathology GA 201QO UT WOS:000248847900020 ER PT J AU Thomas, SH AF Thomas, Stephen H. TI Fentanyl in the prehospital setting SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ANALGESIA; TRAUMA; SEDATION; CITRATE; SAFETY; PAIN C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Emergency Serv, Boston MedFlight, Boston, MA USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. EM thomas.stephen@mgh.harvard.edu NR 21 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD SEP PY 2007 VL 25 IS 7 BP 842 EP 843 DI 10.1016/j.ajem.2007.02.010 PG 2 WC Emergency Medicine SC Emergency Medicine GA 216SF UT WOS:000249898600021 PM 17870493 ER PT J AU Weisskopf, MG O'Reilly, E Chen, H Schwarzschild, MA Ascherio, A AF Weisskopf, M. G. O'Reilly, E. Chen, H. Schwarzschild, M. A. Ascherio, A. TI Plasma urate and risk of Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Parkinson disease; prospective studies; uric acid ID URIC-ACID LEVELS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; BRAIN-BARRIER DYSFUNCTION; MULTIPLE-SCLEROSIS; SUBSTANTIA-NIGRA; PEROXYNITRITE; BLOOD; IRON; CONSUMPTION; PROTECTION AB Oxidative stress contributes to dopaminergic neuron degeneration in Parkinson's disease. Urate, a potent antioxidant, could be neuroprotective. To determine whether higher plasma concentrations of urate predict a reduced risk of Parkinson's disease, the authors conducted a nested case-control study among participants in the Health Professionals Follow-up Study, a cohort comprising over 18,000 men who provided blood samples in 1993-1995. Eighty-four incident cases of Parkinson's disease were diagnosed through 2000, and each was randomly matched to two controls by year of birth, race, and time of blood collection. Rate ratios of Parkinson's disease according to quartile of uricemia were estimated by use of conditional logistic regression. The mean urate concentration was 5.7 mg/dl among cases and 6.1 mg/dl among controls (p = 0.01). After adjustment for age, smoking, and caff eine, the rate ratio of Parkinson's disease for the highest quartile of uricemia compared with the lowest was 0.43 (95% confidence interval: 0.18, 1.02; P-trend = 0.017). This association was stronger in analyses excluding cases diagnosed within 4 years (median) from blood collection (rate ratio = 0.17, 95% confidence interval: 0.04, 0.69; P-trend = 0.010). These results suggest that high plasma urate concentrations may decrease the risk of Parkinson's disease, and they raise the possibility that interventions to increase plasma urate may reduce the risk and delay the progression of Parkinson's disease. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Weisskopf, MG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr,3rd Floor E,POB 15697, Boston, MA 02215 USA. EM mweissko@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NIEHS NIH HHS [K01 ES012653, K01 ES012653-01]; NINDS NIH HHS [R01 NS048517, R01 NS048517-01A2] NR 39 TC 156 Z9 168 U1 1 U2 18 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 1 PY 2007 VL 166 IS 5 BP 561 EP 567 DI 10.1093/aje/kwm127 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 203YT UT WOS:000249010700010 PM 17584757 ER PT J AU Meeker, JD Missmer, SA Vitonis, AF Cramer, DW Hauser, R AF Meeker, John D. Missmer, Stacey A. Vitonis, Allison F. Cramer, Daniel W. Hauser, Russ TI Risk of spontaneous abortion in women with childhood exposure to parental cigarette smoke SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE abortion; spontaneous; maternal exposure; parents; risk; tobacco smoke pollution; women ID ENVIRONMENTAL TOBACCO-SMOKE; IN-UTERO EXPOSURE; SPERM COUNTS; MATERNAL SMOKING; POPULATION; HEALTH AB There is increasing concern over whether environmental exposures early in life may impact health in adulthood. Recent evidence suggests that prenatal or childhood exposure to cigarette smoke may result in poorer reproductive health later in life. Among 2,162 nonsmoking women recruited from three Boston, Massachusetts, clinics who underwent assisted reproductive treatments between 1994 and 2003, adjusted odds ratios for pregnancy outcomes in the initial treatment cycle were calculated in relation to self-reported childhood exposure to parental cigarette smoke. Women who reported having two parents who smoked during their childhood had increased odds of a spontaneous abortion compared with women reporting that neither parent smoked (adjusted odds ratio = 1.8, 95% confidence interval: 1.0, 3.0). A trend for increased risk was observed for women reporting that zero, one, or two parents smoked. In secondary,analysis, the authors also found suggestive evidence for increased risk of failed embryo implantation among women reporting current secondhand tobacco smoke exposure. Future large studies of pregnancy loss are needed that can distinguish women's tobacco smoke exposure in childhood from that taking place in utero. C1 Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Androl Lab, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 6635 SPH Tower,109 S Observ St, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu OI Meeker, John/0000-0001-8357-5085 FU NICHD NIH HHS [R01-HD32153]; NIEHS NIH HHS [R01-ES013967] NR 14 TC 16 Z9 16 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 1 PY 2007 VL 166 IS 5 BP 571 EP 575 DI 10.1093/aje/kwm128 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 203YT UT WOS:000249010700012 PM 17566062 ER PT J AU Burgio, KL Borello-France, D Richter, HE FitzGerald, MP Whitehead, W Handa, VL Nygaard, I Fine, P Zyczynski, H Visco, AG Brown, MB Weber, AM AF Burgio, Kathryn L. Borello-France, Diane Richter, Holly E. FitzGerald, Mary Pat Whitehead, William Handa, Victoria L. Nygaard, Ingrid Fine, Paul Zyczynski, Halina Visco, Anthony G. Brown, Morton B. Weber, Anne M. CA Pelvic Floor Disorders Network TI Risk factors for fecal and urinary incontinence after childbirth: The childbirth and pelvic symptoms study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ANAL-SPHINCTER DISRUPTION; VAGINAL DELIVERY; WOMEN; PREVALENCE; PREGNANCY; OLDER; MODE AB OBJECTIVE: To identify risk factors for postpartum FI and UI. METHODS: Secondary analysis of data from the CAPS study, which estimated the prevalence of postpartum FI and UI in primiparous women with clinically recognized anal sphincter tears after vaginal delivery, compared with women who delivered vaginally without recognized tears or by cesarean before labor. A total of 921 women were enrolled while in the hospital and 759 (82%) were interviewed by telephone 6 months postpartum. FI was assessed using the FISI and UI using the Medical, Epidemiological, and Social Aspects of Aging Questionnaire. FI risk factor analyses were conducted within each group, because of higher prevalence in the tear group. UI analyses were conducted with the groups combined. RESULTS: In women with sphincter tears, FI at 6 months was associated with white race (OR 6.1, 95% CI 1.3-29.4), antenatal UI (OR 2.2, CI 1.1-4.3), 4th versus 3rd degree tear (OR 2.0, CI 1.0-4.0), older age at delivery (OR 1.6 per 5 yr, CI 1.2-2.1), and higher body mass index (BMI) (OR 1.3 per 5 kg/m(2), CI 1.0-1.7). No factors were associated with FI in the vaginal or cesarean control groups. Across all groups, risk factors for postpartum UI were antenatal UI (OR 3.5, CI 2.4-5.2), less education (OR 2.0, CI 1.4-2.8), and higher BMI (OR 1.2 per 5 kg/m(2), CI 1.1-1.4); cesarean delivery was protective (OR 0.5, CI 0.3-0.9). CONCLUSIONS: Postpartum FI and UI are associated with few modifiable risk factors. However, the presence of antenatal UI and high BMI may help clinicians target at-risk women for early intervention. C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. Duquesne Univ, Pittsburgh, PA 15219 USA. Loyola Univ, Chicago, IL 60611 USA. Univ N Carolina, Chapel Hill, NC USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Utah, Salt Lake City, UT USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Michigan, Ann Arbor, MI 48109 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Burgio, KL (reprint author), Univ Alabama, Birmingham, AL 35294 USA. FU NICHD NIH HHS [U10 HD41268, U10 HD41250, U10 HD041263, U10 HD41263, U10 HD41248, U10 HD041261, U01 HD41249, U10 HD41269, U10 HD41261, U10 HD41267] NR 21 TC 43 Z9 46 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2007 VL 102 IS 9 BP 1998 EP 2004 DI 10.1111/j.1572-0241.2007.01364.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 202SA UT WOS:000248922500024 PM 17573795 ER PT J AU Amaratunge, H Tran, T Lu, L Qureshi, WA AF Amaratunge, Harshinie Tran, Thomas Lu, Lee Qureshi, Waqar A. TI Metastatic cholangiocarcinoma presenting as left shoulder pain SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 12-17, 2007 CL Philadelphia, PA SP Amer Coll Gastroengerol C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2007 VL 102 SU 2 MA 504 BP S301 EP S301 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 209OL UT WOS:000249397800502 ER PT J AU Brugge, WR Collier, K McGreevy, K Schmidt, M DeWitt, J AF Brugge, William R. Collier, Kerry McGreevy, Kathleen Schmidt, Max DeWitt, John TI Ethanol pancreatic injection of cysts: Results of a prospective multicenter, randomized, double blinded study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 12-17, 2007 CL Philadelphia, PA SP Amer Coll Gastroengerol C1 Indiana Univ, Indianapolis, IN 46204 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2007 VL 102 SU 2 MA 209 BP S192 EP S193 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 209OL UT WOS:000249397800209 ER PT J AU Gross, RG Reiter, B Korsten, MA AF Gross, Rebekah G. Reiter, Bruce Korsten, Mark A. TI Pyogenic liver abscess complicating colonoscopic polypectomy SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 12-17, 2007 CL Philadelphia, PA SP Amer Coll Gastroengerol C1 Mt Sinai Sch Med, New York, NY USA. James J Peters Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2007 VL 102 SU 2 MA 815 BP S418 EP S419 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 209OL UT WOS:000249397800813 ER PT J AU Lin, WT Hornick, JL Dze, RD Mino-Kenudson, M Lauwers, GY Goyal, RK AF Lin, Weitian Hornick, Jason L. Dze, Robert D. Mino-Kenudson, Mari Lauwers, Gregory Y. Goyal, Raj K. TI Photodynamic therapy decreases DNA content abnormalities in residual non-dysplastic Barrett's esophagus SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 12-17, 2007 CL Philadelphia, PA SP Amer Coll Gastroengerol C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vet Affairs Med Ctr, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2007 VL 102 SU 2 BP S120 EP S120 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 209OL UT WOS:000249397800006 ER PT J AU Sands, B Siegel, C Ozdemir, S Hass, S Miller, D AF Sands, B. Siegel, C. Ozdemir, S. Hass, S. Miller, D. TI Gastroenterologists' tolerance for Crohn's disease treatment risks SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 12-17, 2007 CL Philadelphia, PA SP Amer Coll Gastroengerol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RTI Int, Res Triangle Pk, NC USA. Elan Pharmaceut, San Diego, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2007 VL 102 SU 2 MA 1020 BP S492 EP S492 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 209OL UT WOS:000249397801015 ER PT J AU Toracchio, S El-Zimaity, H Urmacher, C Katz, S Graham, DY AF Toracchio, Sonia El-Zimaity, Hala Urmacher, Carlos Katz, Seymour Graham, David Y. TI Mycobacterium paratuberculosis in Crohn's Disease granulomas SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 12-17, 2007 CL Philadelphia, PA SP Amer Coll Gastroengerol C1 Baylor Coll Med, Houston, TX 77030 USA. CBL Path Inc, Rye Brook, NY USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2007 VL 102 SU 2 MA 932 BP S460 EP S461 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 209OL UT WOS:000249397800930 ER PT J AU Balsis, S Woods, CM Gleason, MEJ Oltmanns, TF AF Balsis, Steve Woods, Carol M. Gleason, Marci E. J. Oltmanns, Thomas F. TI Overdiagnosis and underdiagnosis of personality disorders in older adults SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE age bias; item response theory; personality disorder ID UNITED-STATES; AGE; PREVALENCE AB Objective: Recent evidence suggests that some of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition personality disorder ( PD) criteria contain measurement bias across age groups. Specifically, this research showed that younger and older adults were differentially likely to endorse certain PD criteria, even when both groups were statistically matched using mechanisms of item response theory ( IRT) for degree of PD pathology. For the analyses presented here, the authors used data from a large epidemiological study ( N = 43,093), the National Epidemiologic Survey on Alcohol and Related Conditions, to examine the influence of this item-level measurement bias for reaching accurate algorithmic PD diagnoses of older adults. Methods: Joint probability analyses were used to determine the net effect of the item-level bias on the possible over-or underdiagnosis of six PDs in older adults. Results: When older adults were compared to younger adults at equivalent levels of PD pathology, they were more likely to receive diagnoses of obsessive-compulsive and schizoid PDs. In contrast, they were less likely to receive diagnoses of avoidant and dependent PDs. Younger and older adults were equally likely to receive diagnoses of histrionic and paranoid PDs. Of the seven PDs assessed in this dataset, only these six lend themselves to this type of analysis; antisocial PD differs because a diagnosis depends upon the presence of conduct disorder. Conclusion: These findings raise concerns regarding the interpretation of existing older adult PD prevalence data. C1 Washington Univ, Vet Affairs Med Ctr, St Louis, MO USA. Washington Univ, Dept Psychol, St Louis, MO 63130 USA. RP Balsis, S (reprint author), Houston VA Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM smbalsis@wustl.edu FU NIMH NIH HHS [F31 MH075336, R01 MH077840, R01-MH51187, 1F31-MH075336-01A1, R01 MH051187] NR 22 TC 24 Z9 24 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SEP PY 2007 VL 15 IS 9 BP 742 EP 753 DI 10.1097/JGP.0b013e31813c6b4e PG 12 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 207WO UT WOS:000249282000003 PM 17804828 ER PT J AU Fisher, LB Winickoff, JP Camargo, CA Colditz, GA Frazier, AL AF Fisher, Laurie B. Winickoff, Jonathan P. Camargo, Carlos A., Jr. Colditz, Graham A. Frazier, A. Lindsay TI Household smoking adolescent smoking SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE adolescent; smoking; household policy; household restriction; parental smoking; tobacco promotional items; peer smoking; prevention research ID ANTISMOKING PARENTING PRACTICES; ENVIRONMENTAL TOBACCO-SMOKE; CIGARETTE-SMOKING; WORKPLACE SMOKING; SUBSTANCE USE; RESTRICTIONS; BEHAVIOR; ATTITUDES; SOCIALIZATION; ASSOCIATION AB Purpose. To examine the association between household smoking restrictions and adolescent smoking, controlling for parental smoking, peer smoking, and tobacco marketing. Design. Cross-sectional analysis of 1999 data from the Growing bp Today Study, a longitudinal cohort of adolescents. Setting. Self-report questionnaire. Subjects. 10,593 adolescents aged 12 to 18 years. Measures. The dependent variable was established smoking (smoking >= 100 cigarettes). Variables of interest were household smoking restrictions, parental smoking, peer smoking, and tobacco promotional item (TPI) possession. Results. Four percent of participants reported that their households permitted smoking. Parental smoking, peer smoking. and TPI possession were significantly associated with established smoking. In logistic regression models adjusted for age, gender, peer smoking, and TPI possession, adolescent smoking was inversely related to the presence of a restrictive household policy (odds ratio [OR] 0.67, 95 % confidence internal [CI] = 0.48-0.93); however, when parental smoking was added to this model, the association was attenuated (OR = 0.94, CI = 0.65-1.35). When only one parent in the household smoked, smoking restrictions were more common when this parent was the father. Conclusions. Although household smoking restrictions offer health benefits, they do not appear to be associated with adolescent smoking after accounting for other factors. Prior studies did not include parental smoking, peer smoking, and marketing influences. This analytic difference may explain apparent contradictions in the literature. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management & Epidemiol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. RP Fisher, LB (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM laurie.fisher@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NHLBI NIH HHS [HL-62841] NR 39 TC 13 Z9 13 U1 5 U2 5 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD SEP-OCT PY 2007 VL 22 IS 1 BP 15 EP 21 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 207AR UT WOS:000249224500005 PM 17894258 ER PT J AU Hunt, MK Stoddard, AM Kaphingst, KA Sorensen, G AF Hunt, Mary K. Stoddard, Anne M. Kaphingst, Kimberly A. Sorensen, Glorian TI Characteristics of participants in a cancer prevention intervention designed for multiethnic workers in small manufacturing Worksites SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE health promotion; workplace; prevention research ID HEALTH-PROMOTION; WORKING-CLASS; POPULATIONS; DIRECTIONS; SMOKING; MODEL AB Purpose. To examine worker characteristics explicated in our social-contextual intervention model that might be associated with participation in a cancer Prevention intervention. These characteristics included sociodemographic variables, mediating mechanisms, and modifying conditions. Methods. Randomized, controlled study in. 24 small multiethnic manufacturing worksites. Analyses were conducted on an embedded cohort, of 456 employees in the intervention condition, incorporating the clustering of respondents in worksites using generalized linear mixed modeling methods. The intervention was based on an inclusive, comprehensive social-contextual model targeting fruit, vegetable, and red meat consumption, multivitamin use, and physical activity. Results. Gender (p = .02) and self-efficacy (p < .01) were associated with participation. There Were no differences in participation by race/ethnicity or occupational status. We observed no associations between participation of individual workers in intervention activities and health behavior change. Conclusions. The intervention attracted workers across racial/ethnic and occupational groups. The combination of a comprehensive intervention with wide diffusion of program messages may have been more powerful in influencing participation (and behavior change than characteristics of individual employees. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02172 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Hunt, MK (reprint author), 221 Stn Circle N, Hudson, WI 54016 USA. EM huntmk@comcast.com FU NCI NIH HHS [P01 CA 75308] NR 24 TC 4 Z9 4 U1 0 U2 0 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD SEP-OCT PY 2007 VL 22 IS 1 BP 33 EP 37 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 207AR UT WOS:000249224500008 PM 17894261 ER PT J AU Park, JH Spitzer, T Kuter, DJ AF Park, Jae H. Spitzer, Thomas Kuter, David J. TI Successful treatment of pure red cell aplasia with autologous stem cell transplantation SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID AUTOIMMUNE-DISEASES; THERAPY; PATHOPHYSIOLOGY; PRCA AB We report a case of 64-year-old patient with pure red cell aplasia (PRCA) who was intolerant of conventional immunosuppressive therapies but achieved a complete long-term remission following autologous hematologic stem cell transplant (HSCT). The patient was initially treated with high-dose prednisone, cyclophosphamide, cyclosporine, antithymocyte globulin, and then rituximab. With the exception of rituximab, all of the above regimens achieved a transient response. However, because of the persistent requirement for red blood cell transfusions and intolerance to the multiple immunosuppressive therapies, autologous HSCT was eventually performed. The patient remains in complete remission and on no other therapy for 36 months following the autologous HSCT. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Unit,MGH Canc Ctr, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Unit,MGH Canc Ctr, Yawkey 7940,55 Fruit St, Boston, MA 02114 USA. EM kuter.david@MGH.harvard.edu FU NHLBI NIH HHS [HL72299, HL82889] NR 11 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2007 VL 82 IS 9 BP 812 EP 814 DI 10.1002/ajh.20975 PG 3 WC Hematology SC Hematology GA 208AX UT WOS:000249293300009 PM 17546635 ER PT J AU Zangari, M Esseltine, D Cavallo, F Neuwirth, R Elice, F Burns, MJ Yaccoby, S Richardson, P Sonneveld, P Tricot, G AF Zangari, Maurizio Esseltine, Dixie Cavallo, Federica Neuwirth, Rachel Elice, Francesca Burns, Michael J. Yaccoby, Shmuel Richardson, Paul Sonneveld, Pieter Tricot, Guido TI Predictive value of alkaline phosphatase for response and time to progression in bortezomib-treated multiple myeloma patients SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID OSTEOBLASTS AB Myeloma bone disease is characterized by osteolytic destruction associated with suppressed osteoblastic activity. Using data from the APEX (Richardson et al., N Engl J Med 2005;352:2487-2498) study, we have assessed the relationship of changes in alkaline phosphatase (ALP) levels during bortezomilb therapy with response and time to progression on this therapy. The percentage of ALP increments in responders (complete and partial response) and nonresponders was analyzed at different thresholds and time points. For all bortezomib-treated patients enrolled in the trial (N = 333), at least a 25% increase in ALP from the baseline at 6 week was the most powerful predictor of treatment response (P < 0.0001) and time to progression (206 vs. 169 days) relative to patients with less than a 25% increase in ALP (P = 0.01). Markers of osteoblastic activation may predict quality and duration of response in multiple myeloma. In addition, our data suggest that bone anabolism could inhibit myeloma growth. C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. Millennium Pharmaceut Co, Cambridge, MA USA. San Bortolo Hosp, Dept Hematol, Vicenza, Italy. Univ Rotterdam Hosp, Dept Hematol, Rotterdam, Netherlands. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zangari, M (reprint author), 4301 W Markham St,Slot 776, Little Rock, AR 72205 USA. EM zangarimaurizio@uams.edu NR 11 TC 19 Z9 19 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2007 VL 82 IS 9 BP 831 EP 833 DI 10.1002/ajh.20961 PG 3 WC Hematology SC Hematology GA 208AX UT WOS:000249293300014 PM 17546639 ER PT J AU Purcell, S Neale, B Todd-Brown, K Thomas, L Ferreira, MAR Bender, D Maller, J Sklar, P de Bakker, PIW Daly, MJ Sham, PC AF Purcell, Shaun Neale, Benjamin Todd-Brown, Kathe Thomas, Lori Ferreira, Manuel A. R. Bender, David Maller, Julian Sklar, Pamela de Bakker, Paul I. W. Daly, Mark J. Sham, Pak C. TI PLINK: A tool set for whole-genome association and population-based linkage analyses SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FAMILY-BASED ASSOCIATION; GENETIC ASSOCIATION; QUANTITATIVE TRAITS; COMPLEX DISEASES; WIDE ASSOCIATION; STRATIFICATION; SCALE; VARIANTS; SEGMENTS; HISTORY AB Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA. Univ London, Inst Psychiat, London, England. Univ Hong Kong, Ctr Gene Res, Hong Kong, Hong Kong, Peoples R China. RP Purcell, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Room 6-254,CPZ N,185 Cambridge St, Boston, MA 02114 USA. EM Shaun@pngu.mgh.harvard.edu RI Sincan, Murat /A-3794-2010; Ferreira, Manuel/D-3609-2013; de Bakker, Paul/B-8730-2009; OI de Bakker, Paul/0000-0001-7735-7858; Maller, Julian/0000-0002-1565-9559; Todd-Brown, Katherine/0000-0002-3109-8130 FU NEI NIH HHS [R01 EY012562, EY-12562]; NHGRI NIH HHS [U01 HG004171]; NIMH NIH HHS [R03 MH073806, R03 MH73806-01A1] NR 39 TC 9115 Z9 9266 U1 92 U2 477 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 2007 VL 81 IS 3 BP 559 EP 575 DI 10.1086/519795 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 205PX UT WOS:000249128200012 PM 17701901 ER PT J AU Petersen, LA Urech, TH Byrne, MM Pietz, K AF Petersen, Laura A. Urech, Tracy H. Byrne, Margaret M. Pietz, Kenneth TI Do financial incentives in a globally budgeted healthcare payment system produce changes in the way patients are categorized? A five-year study SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID PAY-FOR-PERFORMANCE; REGIONAL-VARIATIONS; MEDICARE PATIENTS; QUALITY; OUTCOMES; IMPLEMENTATION; HOSPITALS; UNDERUSE AB Objective: To assess the responses to financial incentives after a change in the payment system in a capitation-style healthcare payment system over a 5-year period. Study Design: Cross-sectional and longitudinal examination of cost, utilization, and diagnostic data. Methods: Using Veterans Health Administration (VHA) administrative data on healthcare users between fiscal years 1998 and 2002, we calculated the proportion of new patients entering each of the payment classes, the illness burden of patients entering the payment classes, and the profitability index (a ratio of payment to costs) for each class suspected of gaming and each control class. Our main dependent variables of interest were the differences in the measures between each utilization-based class and each diagnosis-based class. We used 2 different analytic approaches to assess whether these differences increased or decreased over time. Results: No clear evidence of gaming behavior was present in our results. A few comparisons were significant, but they did not show a consistent pattern of responses to incentives. For example, 6 of 16 comparisons of profitability index were significant, but (contrary to the hypothesis) 4 of these had a negative value for the time parameter, indicating decreasing profitability in the utilization-based classes versus the diagnosis-based classes. Conclusions: Although the payment system could be manipulated to increase payment to VHA networks, no such consistent gaming behavior was observed. More research is needed to better understand the effects of financial incentives in other healthcare payment systems. C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Hlth Serv Res & Dev 152, Div Hlth Policy & Qual,Houston Ctr Qual Care & Ut, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ Miami, Dept Epidemiol & Publ Hlth, Miami, FL 33152 USA. RP Petersen, LA (reprint author), Baylor Coll Med, Houston Vet Affairs Med Ctr, Hlth Serv Res & Dev 152, Div Hlth Policy & Qual,Houston Ctr Qual Care & Ut, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM laurap@bcm.tmc.edu FU NHLBI NIH HHS [R01 HL079173-01] NR 34 TC 5 Z9 5 U1 1 U2 4 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD SEP PY 2007 VL 13 IS 9 BP 513 EP 522 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 210JN UT WOS:000249452600003 PM 17803365 ER PT J AU Li, JZ Winston, LG Moore, DH Bent, S AF Li, Jonathan Z. Winston, Lisa G. Moore, Dan H. Bent, Stephen TI Efficacy of short-course antibiotic regimens for community-acquired pneumonia: A meta-analysis SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 46th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 27-30, 2006 CL San Francisco, CA DE antibiotics; community-acquired pneumonia; pneumonia; short-course ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; RANDOMIZED CONTROLLED-TRIALS; ANTIMICROBIAL THERAPY; ATYPICAL PNEUMONIA; CLINICAL-EFFICACY; UNITED-STATES; AZITHROMYCIN; ADULTS; GUIDELINES; MANAGEMENT AB PURPOSE: There is little consensus on the most appropriate duration of antibiotic treatment for community-acquired pneumonia. The goal of this study is to systematically review randomized controlled trials comparing short-course and extended-course antibiotic regimens for community-acquired pneumonia. METHODS: We searched MEDLINE, Embase, and CENTRAL, and reviewed reference lists from 1980 through June 2006. Studies were included if they were randomized controlled trials that compared short-course (7 days or less) versus extended-course (> 7 days) antibiotic monotherapy for community-acquired pneumonia in adults. The primary outcome measure was failure to achieve clinical improvement. RESULTS: We found 15 randomized controlled trials matching our inclusion and exclusion criteria comprising 2796 total subjects. Short-course regimens primarily studied the use of azithromycin (n = 10), but trials examining beta-lactams (n = 2), fluoroquinolones (n = 2), and ketolides (n = 1) were found as well. Of the extended-course regimens, 3 studies utilized the same antibiotic, whereas 9 involved an antibiotic of the same class. Overall, there was no difference in the risk of clinical failure between the short-course and extended-course regimens (0.89, 95% confidence interval [CI], 0.78-1.02). In addition, there were no differences in the risk of mortality (0.81, 95% CI, 0.46-1.43) or bacteriologic eradication (1.11, 95% CI, 0.76-1.62). In subgroup analyses, there was a trend toward favorable clinical efficacy for the short-course regimens in all antibiotic classes (range of relative risk, 0.88-0.94). CONCLUSIONS: The available studies suggest that adults with mild to moderate community-acquired pneumonia can be safely and effectively treated with an antibiotic regimen of 7 days or less. Reduction in patient exposure to antibiotics may limit the increasing rates of antimicrobial drug resistance, decrease cost, and improve patient adherence and tolerability. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Infect Dis Sect, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA 94143 USA. RP Li, JZ (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, Box 0862,5H22, San Francisco, CA 94143 USA. EM jli22@partners.org NR 59 TC 66 Z9 71 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2007 VL 120 IS 9 BP 783 EP 790 DI 10.1016/j.amjmed.2007.04.023 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 205ON UT WOS:000249123800012 PM 17765048 ER PT J AU Rudolph, JL Jones, RN Rasmussen, LS Silverstein, JH Inouye, SK Marcantonio, ER AF Rudolph, James L. Jones, Richard N. Rasmussen, Lars S. Silverstein, Jeffrey H. Inouye, Sharon K. Marcantonio, Edward R. TI Independent vascular and cognitive risk factors for postoperative delirium SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE atherosclerosis; cognition; delirium; risk factors; surgery; tobacco; vascular surgery ID BYPASS GRAFT-SURGERY; NONCARDIAC SURGERY; DYSFUNCTION; IMPAIRMENT; DEMENTIA; SYMPTOMS; DISEASE; HEALTH; CARE; AGE AB BACKGROUND: Delirium is a common, morbid, and costly syndrome that occurs frequently after surgery for atherosclerosis. We hypothesized that vascular risk factors and mildly impaired cognitive performance would independently predispose nondemented patients to develop delirium after noncardiac surgery. METHODS: The International Study of Postoperative Cognitive Dysfunction recruited patients undergoing noncardiac surgery from 8 countries. Subjects provided detailed medical history and underwent preoperative testing of multiple cognitive domains with a neuropsychologic battery. Postoperatively, subjects (n = 1161) were assessed daily for delirium. RESULTS: Ninety-nine subjects (8%) developed delirium. In bivariable analysis, several vascular risk factors were significantly associated with the likelihood of delirium, including male sex, exposure to tobacco, previous myocardial infarction, and vascular surgery. After adjustment for age, tobacco exposure and vascular surgery were independent vascular risk factors for delirium (adjusted relative risk [RR] 3.2, 95% confidence interval [CI], 2.1-4.9). In addition, mildly impaired cognitive performance, defined as performance 1.5 standard deviation below the mean on either of 2 neuropsychologic tests, was independently associated with delirium (adjusted RR 2.2, 95% CI, 1.4-3.6). Subjects with both vascular risk factors and mildly impaired cognitive performance were at double the risk of delirium (RR 2.2, 95% CI, 1.2-4.2) compared with those with either of these risk factors alone. CONCLUSIONS: Vascular risk and mildly impaired cognitive performance independently predispose patients to delirium after noncardiac surgery. These factors will help to identify high-risk patients for delirium and to design and target future intervention strategies. (C) 2007 Elsevier Inc. All rights reserved. C1 VA Boston Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA. Hebrew SenoirLife, Inst Aging Res, Boston, MA USA. Hebrew SenoirLife, Inst Aging Brain Ctr, Boston, MA USA. Univ Copenhagen Hosp, Ctr Head & Orthopaed, Dept Anesthesia, DK-2100 Copenhagen, Denmark. Mt Sinai Sch Med, Dept Anesthesiol, New York, NY USA. Mt Sinai Sch Med, Dept Surg, New York, NY USA. Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. VABHS, Boston, MA 02130 USA. RP Rudolph, JL (reprint author), VABHS, JP-182,150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org RI Jones, Richard/J-3488-2013; OI Jones, Richard/0000-0002-1049-218X; Rasmussen, Lars/0000-0002-7480-3004 FU NIA NIH HHS [R21AG025193, 5 K12 AG00294-18, 5 P60 AG08812-14, K24AG000949, R01AG018772-04] NR 39 TC 61 Z9 65 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2007 VL 120 IS 9 BP 807 EP 813 DI 10.1016/j.amjmed.2007.02.026 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 205ON UT WOS:000249123800015 PM 17765051 ER PT J AU Seidenwurm, D Turski, P Barr, J Connors, J Lev, M Mukherji, S Russell, E AF Seidenwurm, D. Turski, P. Barr, J. Connors, J. Lev, M. Mukherji, S. Russell, E. TI Performance measures in neuroradiology SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CAROTID-ARTERY STENOSIS; PAY-FOR-PERFORMANCE; HEALTH-CARE; ISCHEMIC-STROKE; QUALITY; ENDARTERECTOMY; ULTRASOUND; MORTALITY; STATES; US AB Performance measurement has been added to the Medicare payment scheme as of July 2007. Two performance measures are applicable to neuroradiology, pertaining to brain and vascular imaging in stroke. These measures are early attempts to rigorously define the meaning of effective performance of neuroradiology. C1 Radiol Associates Sacramento, Sacramento, CA 95816 USA. Univ Wisconsin, Madison, WI USA. Baptist Mem Hosp, Memphis, TN 38146 USA. Miami Vasc Inst, Miami, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Northwestern Univ, Chicago, IL 60611 USA. RP Seidenwurm, D (reprint author), Radiol Associates Sacramento, 1500 Expo Pkwy, Sacramento, CA 95816 USA. EM dseidenwurm@comcast.net NR 27 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2007 VL 28 IS 8 BP 1435 EP 1438 DI 10.3174/ajnr.A0672 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 213DC UT WOS:000249645300008 PM 17846186 ER PT J AU Jensen, ME McGraw, JK Cardella, JF Hirsch, JA AF Jensen, M. E. McGraw, J. K. Cardella, J. F. Hirsch, J. A. TI Position statement on percutaneous vertebral augmentation: A consensus statement developed by the American society of interventional and therapeutic neuroradiology, society of interventional radiology, American association of neurological surgeons/congress of neurological surgeons, and American society of spine radiology SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID OSTEOPOROTIC COMPRESSION FRACTURES; BALLOON KYPHOPLASTY; FOLLOW-UP; POLYMETHYLMETHACRYLATE VERTEBROPLASTY; PULMONARY-EMBOLISM; CLINICAL-OUTCOMES; ACRYLIC CEMENT; PAIN RELIEF; BED REST; COMPLICATIONS C1 Riverside Methodist Hosp, Columbus, OH 43214 USA. Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McGraw, JK (reprint author), Riverside Methodist Hosp, 3525 Olentangy River Rd,Ste 5362, Columbus, OH 43214 USA. EM jkmcgraw@hotmail.com NR 68 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2007 VL 28 IS 8 BP 1439 EP 1443 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 213DC UT WOS:000249645300009 PM 17846187 ER PT J AU Hara, K Lin, FH Camposano, S Foxe, DM Grant, PE Bourgeois, BF Ahlfors, SP Stufflebearn, SM AF Hara, K. Lin, F.-H. Camposano, S. Foxe, D. M. Grant, P. E. Bourgeois, B. F. Ahlfors, S. P. Stufflebearn, S. M. TI Magnetoencephalographic mapping of interictal spike propagation: A technical and clinical report SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID EPILEPSY; MEG AB Distinguishing propagated epileptic activity from primary epileptic foci is of critical importance in presurgical evaluation of patients with medically intractable focal epilepsy. We studied an 1 1-year-old patient with complex partial epilepsy by using simultaneous magnetoencephalography (MEG) and electroencephalography (EEG). In EEG, bilateral interictal discharges appeared synchronous, whereas MEG source analysis suggested propagation of spikes from the right to the left frontal lobe. C1 Massachusetts Gen Hosp East, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. Childrens Hosp, Div Epilepsy & Clin Neurophysiol, Boston, MA 02115 USA. RP Lin, FH (reprint author), Massachusetts Gen Hosp East, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM fhlin@ntu.edu.tw RI Lin, Fa-Hsuan/G-6988-2012; Ahlfors, Seppo/P-3644-2016 OI Lin, Fa-Hsuan/0000-0002-9539-1731; FU NCRR NIH HHS [P41 RR14075] NR 13 TC 7 Z9 9 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2007 VL 28 IS 8 BP 1486 EP 1488 DI 10.3174/ajnr.A0596 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 213DC UT WOS:000249645300018 PM 17846196 ER PT J AU Nakao, S Hata, Y Miura, M Noda, K Kimura, YN Kawahara, S Kita, T Hisatomi, T Nakazawa, T Jin, Y Dana, MR Kuwano, M Ono, M Ishibashi, T Hafezi-Moghadam, A AF Nakao, Shintaro Hata, Yasuaki Miura, Muneki Noda, Kousuke Kimura, Yusuke N. Kawahara, Shulhei Kita, Takeshi Hisatomi, Toshio Nakazawa, Tonu Jin, Yiping Dana, M. Reza Kuwano, Michihiko Ono, Mayumi Ishibashi, Tatsuro Hafezi-Moghadam, Ali TI Dexamethasone inhibits interleukin-1 beta-induced corneal neovascularization - Role of nuclear factor-kappa B-activated stromal cells in inflammatory angiogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-GROWTH; ANGIOSTATIC STEROIDS; CHEMOKINE RECEPTOR; IN-VIVO; FIBROBLASTS; EXPRESSION; DISEASE; CARCINOMA; KERATITIS; CANCER AB Dexamethasone, a synthetic corticosteroid, is widely used as a potent anti-inflammatory drug in various diseases including corneal angiogenesis. However, dexamethasone's impact on interleukin (IL)-1 beta-dependent inflammatory angiogenesis is unknown. Here, we show that dexamethasone inhibits IL-beta-induced neovascularization and the expression of the angiogenesis-related factors, vascular endothelial growth factor-A, KC, and prostaglandin E, in the mouse cornea 2 days after IL-1 beta implantation. IL-1 beta caused I kappa B-alpha phosphorylation in corneal stromal cells but not in infiltrated CD11b(+) cells 2 days after IL-1 beta implantation. In contrast, both cell types were positive for phosphorylated I kappa B-alpha 4 days after IL-1 beta,6 implantation. Dexamethasone significantly inhibited lic&a phosphorylation 2 and 4 days after IL-1 beta implantation. Furthermore, dexamethasone inhibited IL-1 beta-induced expression of vascular endothelial growth factor-A, KC, and prostaglandin E-2, and signaling of nuclear factor (NF)-kappa B in corneal fibroblasts in vitro. A selective NF-kappa B inhibitor attenuated IL-1 beta-in- duced corneal angiogenesis. These findings suggest that NF-kappa B activation in the corneal stromal cells is an important early event during IL-1 beta-induced corneal angiogenesis and that dexamethasone inhibits IL-1 beta-induced angiogenesis partially via blocking NF-KB signaling. C1 Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan. Kyushu Univ, Grad Sch Med Sci, Dept Med Biochem, Fukuoka 8128582, Japan. Kyushu Univ, Grad Sch Med Sci, Collabo Stn 2, Fukuoka 8128582, Japan. Kurume Univ, Res Ctr Innovat Canc Therapy Century 21, COE, Program Med Sci, Fukuoka, Japan. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Hata, Y (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM hatachan@med.kyushu-u.ac.jp RI U-ID, Kyushu/C-5291-2016; OI Hisatomi, Toshio/0000-0003-2552-9595; Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NEI NIH HHS [EY14104, EY12963, P30 EY014104, R01 EY012963]; NIAID NIH HHS [K08 AI050775] NR 42 TC 56 Z9 61 U1 0 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2007 VL 171 IS 3 BP 1058 EP 1065 DI 10.2353/ajpath.2007.070172 PG 8 WC Pathology SC Pathology GA 205WV UT WOS:000249146200032 PM 17690185 ER PT J AU Johnson, B Simpson, LL AF Johnson, Blair Simpson, Lynn L. TI Screening for congenital heart disease: A move toward earlier echocardiography SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE fetal echocardiography; congenital heart disease; fetal heart; prenatal diagnosis; nuchal translucency ID INCREASED NUCHAL TRANSLUCENCY; EARLY FETAL ECHOCARDIOGRAPHY; SEROTONIN REUPTAKE INHIBITORS; CHROMOSOMALLY NORMAL FETUSES; MAJOR CARDIAC DEFECTS; 14 WEEKS GESTATION; PRENATAL-DIAGNOSIS; UNSELECTED POPULATION; GREAT-ARTERIES; MATERNAL USE AB Fetal echocardiography remains the mainstay for diagnosis in those pregnancies identified to be at risk for congenital heart disease (CHD). Prenatal diagnosis of CHD remains essential to provide families with thorough pregnancy options as well as allow for transfer to facilities experienced in the management of pediatric cardiac disease in cases of ongoing pregnancy. First-trimester and early second-trimester fetal echocardiography is now feasible and will be increasingly in demand as enlarged nuchal translucency and first-trimester cystic hygroma are becoming common indications for early fetal echocardiography. Although the reported performance characteristics of early fetal echocardiography are good, the technique should be viewed as an adjunct to mid-trimester echocardiography, with its biggest benefit likely to be the ability to provide earlier reassurance to couples at risk for CHD. Early fetal echocardiograms should be reserved for patients at risk for CHD and be performed in centers experienced in this technique. C1 Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY USA. RP Johnson, B (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. NR 56 TC 14 Z9 14 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD SEP PY 2007 VL 24 IS 8 BP 449 EP 456 DI 10.1055/s-2007-986681 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 217YK UT WOS:000249983000002 PM 17992711 ER PT J AU Glymour, MM Berkman, LF Ertel, KA Fay, ME Glass, TA Furie, KL AF Glymour, M. Maria Berkman, Lisa F. Ertel, Karen A. Fay, Martha E. Glass, Thomas A. Furie, Karen L. TI Lesion characteristics NIH stroke scale, and functional recovery after stroke SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE stroke; NIH stroke scale; Imaging; functional outcomes ID QUALITY-OF-LIFE; ISCHEMIC-STROKE; TREATMENT TOAST; TRIAL 1ST; ORG 10172; HEALTH; RELIABILITY; DISABILITY; DEPRESSION; PREDICTION AB Objective: We examined the relationships between the National Institute of Health Stroke Scale (NIHSS) and physical cognitive and social,, participation outcomes across subpopulations of stroke survivors on the basis of cortical involvement and lesion lateralization. Design: Families in Recovery from Stroke Trial participants were classi fied with respect to lesion lateralization (n = 274) and cortical involvement (n = 158). NIHSS scores (average 13 days after stroke) were used to predict Physical Performance Test times (PPT), limitations In activities of daily living (Augmented Barthel Index (ABI)), Instrumental Activities of Daily Living (IADL), cognitive function, depressive symptoms (Center for Epide-miologic Studies Depression scale [CES-D]), and productive, recreational, self-care, and social role activities 3 and 6 mos later. We compared the relationship between NIHSS and each outcome in stroke subgroups classified by lesion lateralization and cortical involvement. Results: NIHSS predicted physical performance, activities of daily living, and IADL independence. The association between NIHSS and both PPT and IADLs was less steep for patients with cortical lesions than for patients with exclusively subcortical lesions. NIHSS predicted physical performance, activities of daily living, or IADLs similarly for right and left-hemisphere strokes, but hemisphere modified the association between NIHSS and CES-D and cognitive measures. Conclusions: The NIHSS may predict outcomes in subpopulations of stroke survivors with subcortical lesions better than in patients with cortical involvement. NIHSS predicted CES-D in patients with right-sided lesions but not in those with left-sided lesions. In contrast, NIHSS had little associationwith cognitive outcomes among patients without left-side involvement. C1 Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Glymour, MM (reprint author), Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, 722 W 168th St,Room 1603, New York, NY 10032 USA. OI Glass, Thomas/0000-0003-4399-612X FU NINDS NIH HHS [NS032324] NR 33 TC 22 Z9 23 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD SEP PY 2007 VL 86 IS 9 BP 725 EP 733 DI 10.1097/PHM.0b013e31813e0a32 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 205SC UT WOS:000249133900006 PM 17709996 ER PT J AU Chiou-Tan, FY Bloodworth, DM Kass, JS Li, XQ Gavagan, TF Mattox, K Rintala, DH AF Chiou-Tan, Faye Y. Bloodworth, Donna M. Kass, Joseph S. Li, Xiaoqi Gavagan, Thomas F. Mattox, Kenneth Rintala, Diana H. TI Physical medicine and rehabilitation conditions in the astrodome clinic after Hurricane Katrina SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE disaster preparedness; physical medicine and rehabilitation; Hurricane; emergency relief AB Objective: To report the physical medicine and rehabilitation (PMR) conditions seen in the Astrodome Clinic after Hurricane Katrina. Design: Retrospective chart analysis from the county hospital-sponsored disaster-relief clinic in large urban city, including a study of 239 patients with 292 PMR conditions. The total number of patients seen in the Astrodome Medical Clinic was 11,245. The Astrodome database was reviewed for PMR condition diagnostic codes. A retrospective chart analysis was conducted, including date of visit, age, gender, ethnicity, and PMR diagnosis category. Descriptive statistics were obtained for the entire sample. X-2 or t tests were used to determine gender, age, or date-of-service predominance for the most common diagnostic categories. Results: Mean +/- SID age was 45.7 +/- 14.3 yrs; 56% were women, 43% were men (1% unspecified), and 76% were African American. The majority (75%) of PMR conditions presented in the first week. Most frequent were swollen feet and legs (22%), leg pain and cramps (17%), and neck and back pain (10%). Persons with head-headache (112%), aches were younger than those without (41.3 vs. 46.3 yrs, P = 0.048). Persons with neck and/or back pain were older than those without those conditions (51.3 vs. 44.8 yrs, P = 0.004). Women had more headaches (20.9%) than did men (6.7%, P = 0.002). There were no Caucasians with leg pain/cramps, whereas 20.2% of African Americans had this condition (P = 0.028). Conclusions: This study documents the time of clinic presentation and most frequent types of PMR conditions of patients treated in the Astrodome Clinic after a historic hurricane. Most PMR conditions were treated by PMR personnel during the first week. Thus, future disaster planning should include PMR professionals as early responders. C1 Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Res Harris Cty Hosp Dist, Ctr Trauma Rehabil, Houston, TX USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, Ctr Med Eth & Hlth Care Policy, Houston, TX 77030 USA. Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Chiou-Tan, FY (reprint author), Quentin Mease Hosp, Dept Phys Med & Rehabil, 3601 N MacGregor Way,Suite 240, Houston, TX 77004 USA. NR 6 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD SEP PY 2007 VL 86 IS 9 BP 762 EP 769 DI 10.1097/PHM.0b013e31813e61cc PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 205SC UT WOS:000249133900010 PM 17710001 ER PT J AU Arvanitis, DA Vafiadaki, E Fan, GC Mitton, BA Gregory, KN Del Monte, F Kontrogianni-Konstantopoulos, A Sanoudou, D Kranias, EG AF Arvanitis, Demetrios A. Vafiadaki, Elizabeth Fan, Guo-Chang Mitton, Bryan A. Gregory, Kimberly N. Del Monte, Federica Kontrogianni-Konstantopoulos, Aikaterini Sanoudou, Despina Kranias, Evangelia G. TI Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE triadin; calcium cycling ID HEART-FAILURE; GENE-TRANSFER; CA2+-BINDING PROTEIN; RYANODINE RECEPTOR; CALCIUM-PUMP; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; TRIADIN; PHOSPHOLAMBAN; CA2+-ATPASE AB Depressed cardiac Ca cycling by the sarcoplasmic reticulum (SR) has been associated with attenuated contractility, which can progress to heart failure. The histidine-rich Ca-binding protein (HRC) is an SR component that binds to triadin and may affect Ca release through the ryanodine receptor. HRC overexpression in transgenic mouse hearts was associated with decreased rates of SR Ca uptake and delayed relaxation, which progressed to hypertrophy with aging. The present study shows that HRC may mediate part of its regulatory effects by binding directly to sarco(endo) plasmic reticulum Ca-ATPase type 2 (SERCA2) in cardiac muscle, which is confirmed by coimmunostaining observed under confocal microscopy. This interaction involves the histidine- and glutamic acid-rich domain of HRC (320-460 aa) and the part of the NH2-terminal cation transporter domain of SERCA2 (74-90 aa) that projects into the SR lumen. The SERCA2-binding domain is upstream from the triadin-binding region in human HRC (609-699 aa). Specific binding between HRC and SERCA was verified by coimmunoprecipitation and pull-down assays using human and mouse cardiac homogenates and by blot overlays using glutathione S-transferase and maltose-binding protein recombinant proteins. Importantly, increases in Ca concentration were associated with a significant reduction of HRC binding to SERCA2, whereas they had opposite effects on the HRC-triadin interaction in cardiac homogenates. Collectively, our data suggest that HRC may play a key role in the regulation of SR Ca cycling through its direct interactions with SERCA2 and triadin, mediating a fine cross talk between SR Ca uptake and release in the heart. C1 Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA. Acad Athens, SW Fdn Biomed Res, Ctr Basic Res, Div Mol Biol, GR-10673 Athens, Greece. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Boston, MA USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RP Kranias, EG (reprint author), Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM Litsa.Kranias@uc.edu OI Sanoudou, Despina/0000-0003-3704-1941; Vafiadaki, Elizabeth/0000-0001-9931-7099; Arvanitis, Demetrios/0000-0003-1231-320X FU NHLBI NIH HHS [HL-64018, HL-26057, HL-77101] NR 42 TC 45 Z9 47 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2007 VL 293 IS 3 BP H1581 EP H1589 DI 10.1152/ajpheart.00278.2007 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 207FU UT WOS:000249237800034 PM 17526652 ER PT J AU Colston, JT de la Rosa, SD Koehler, M Gonzales, K Mestril, R Freeman, GL Bailey, SR Chandrasekar, B AF Colston, J. T. de la Rosa, S. D. Koehler, M. Gonzales, K. Mestril, R. Freeman, G. L. Bailey, S. R. Chandrasekar, B. TI Wnt-induced secreted protein-1 is a prohypertrophic and profibrotic growth factor SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cysteine-rich 61; connective tissue growth factor; and nephroblastoma; overexpressed family; myocardial infarction; myocardial remodeling; Akt; cardiomyocyte hypertrophy ID ACUTE MYOCARDIAL-INFARCTION; GLYCOGEN-SYNTHASE KINASE-3-BETA; ADULT CARDIAC FIBROBLASTS; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE-CELLS; FACTOR-KAPPA-B; GENE-EXPRESSION; TGF-BETA; PLASMA-CATECHOLAMINES; SIGNALING PATHWAY AB Wnt1-induced secreted protein-1 (WISP-1) is a member of the cysteine-rich 61, connective tissue growth factor, and nephroblastoma overexpressed (CCN) family of growth factors and is expressed in the heart at low basal levels. The purpose of this study was to investigate whether WISP-1 is upregulated in postinfarct myocardium and whether WISP-1 exerts prohypertrophic and mitogenic effects stimulating myocyte hypertrophy, cardiac fibroblast (CF) proliferation, and collagen expression. Male C57B1/6 (25 g) mice underwent permanent occlusion of the left anterior descending coronary artery. mRNA and protein levels were analyzed by Northern and Western blot analyses. Cardiomyocyte hypertrophy was quantified by protein and DNA synthesis. CF proliferation was quantified by CyQuant assay, and soluble collagen release by Sircol assay. A time-dependent increase in WISP-1 expression was detected in vivo in the noninfarct zone of the left ventricle, which peaked at 24 h (3.1-fold, P < 0.01). Similarly, biglycan expression was increased by 3.71-fold (P < 0.01). IL-1 beta and TNF-alpha expression preceded WISP-1 expression in vivo and stimulated WISP-1 expression in neonatal rat ventricular myocytes in vitro. WISP-1- induced cardiomyocyte hypertrophy was evidenced by increased protein (2.78- fold), but not DNA synthesis, and enhanced Akt phosphorylation and activity. Treatment of primary CF with WISP-1 significantly stimulated proliferation at 48 h (6,966 +/- 264 vs. 5,476 +/- 307 cells/ well, P < 0.01) and enhanced collagen release by 72 h (18.4 +/- 3.1 vs. 8.4 +/- 1.0 ng/cell, P < 0.01). Our results demonstrate for the first time that WISP-1 and biglycan are upregulated in the noninfarcted myocardium in vivo, suggesting a positive amplification of WISP-1 signaling. WISP-1 stimulates cardiomyocyte hypertrophy, fibroblast proliferation, and ECM expression in vitro. These results suggest that WISP-1 may play a critical role in post-myocardial infarction remodeling. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Loyola Univ, Med Ctr, Dept Physiol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Cardiovasc Inst, Maywood, IL 60153 USA. Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Chandrasekar, B (reprint author), 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM chandraseka@uthscsa.edu FU NHLBI NIH HHS [HL-67971, HL-68020] NR 56 TC 58 Z9 63 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2007 VL 293 IS 3 BP H1839 EP H1846 DI 10.1152/ajpheart.00428.2007. PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 207FU UT WOS:000249237800065 PM 17616748 ER PT J AU Laudi, S Trump, S Schmitz, V West, J McMurtry, IF Mutlak, H Christians, U Weimann, J Kaisers, U Steudel, W AF Laudi, Sven Trump, Saskia Schmitz, Volker West, James McMurtry, Ivan F. Mutlak, Haitham Christians, Uwe Weimann, Joerg Kaisers, Udo Steudel, Wolfgang TI Serotonin transporter protein in pulmonary hypertensive rats treated with atorvastatin SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE monocrotaline; HMG-CoA-reductase inhibitor; 5-HTT; 5-HT ID SMOOTH-MUSCLE-CELLS; NITRIC-OXIDE SYNTHASE; COA REDUCTASE INHIBITORS; IN-VITRO; INDUCED MEGALOCYTOSIS; LIVER MICROSOMES; LOWERING THERAPY; EPITHELIAL-CELLS; MONOCROTALINE; 5-HYDROXYTRYPTAMINE AB HMG-CoA-reductase inhibitors (statins) influence lipid metabolism and have pleiotropic effects. Several statins reduce various forms of pulmonary hypertension (PH) in animal models. The relationship between atorvastatin and expression of serotonin transporter protein (5-HTT) remains unknown. This study focused on the effects of atorvastatin on the course of monocrotaline (MCT)-induced PH and its relation to 5-HTT expression. Male Sprague-Dawley rats were challenged with MCT with or without subsequent daily oral treatment with 0.1, 1, and 10 mg/kg of atorvastatin for 28 days. Over the 4-wk course, the progression of PH was followed by transthoracic echocardiography [pulmonary artery pressure was assessed by pulmonary artery flow acceleration time (PAAT), an estimate reciprocal to pulmonary artery pressure], and, at the end of the 4-wk course, invasive right ventricular pressure, right ventricular weight, quantitative morphology, and 5-HTT expression were measured. MCT caused significant PH as early as 7 days after injection. Atorvastatin treatment increased PAAT and reduced right ventricular pressure, right ventricular hypertrophy, and vascular remodeling over the 4-wk course. MCT challenge was associated with increased pulmonary vascular 5-HTT expression, and atorvastatin treatment reduced the 5-HTT expression. MCT-induced PH over the course of 4 wk can be easily followed by transthoracic echocardiography, and atorvastatin is effective in reducing the PH. Atorvastatin's effects are associated with a decrease of 5-HTT expression. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Colorado, Dept Anesthesiol Clin Res & Dev, Denver, CO 80202 USA. Univ Colorado, Ctr Genet Lung Dis, Denver, CO 80202 USA. Univ Colorado, Cardiovasc Res Labs, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80206 USA. Vrije Univ Amsterdam, Med Ctr, Dept Anesthesiol, NL-1081 HV Amsterdam, Netherlands. Univ Leipzig, Fac Med, Dept Anesthesiol & Intens Care Med, D-7010 Leipzig, Germany. RP Steudel, W (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Gray Jackson 4, Boston, MA 02114 USA. EM wsteudel@partners.org RI West, James/E-2960-2010 OI West, James/0000-0002-6004-0202 FU NHLBI NIH HHS [R01-HL-071805-02]; PHS HHS [P30-EK-048520-10] NR 66 TC 26 Z9 31 U1 2 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD SEP PY 2007 VL 293 IS 3 BP L630 EP L638 DI 10.1152/ajplung.00110.2006 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 205OV UT WOS:000249125100018 PM 17575010 ER PT J AU Miklowitz, DJ Otto, MW Frank, E Reilly-Harrington, NA Kogan, JN Sachs, GS Thase, ME Calabrese, JR Marangell, LB Ostacher, MJ Patel, J Thomas, MR Araga, M Gonzalez, JM Wisniewski, SR AF Miklowitz, David J. Otto, Michael W. Frank, Ellen Reilly-Harrington, Noreen A. Kogan, Jane N. Sachs, Gary S. Thase, Michael E. Calabrese, Joseph R. Marangell, Lauren B. Ostacher, Michael J. Patel, Jayendra Thomas, Marshall R. Araga, Mako Gonzalez, Jodi M. Wisniewski, Stephen R. TI Intensive psychosocial intervention enhances functioning in patients with bipolar depression: Results from a 9-month Randomized controlled trial SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID AFFECTIVE-DISORDER; SCHIZOPHRENIA; IMPAIRMENT; EFFICACY; THERAPY; RELAPSE; PROGRAM; SCALE; MANIA AB Objective: Psychosocial interventions are effective adjuncts to pharmacotherapy in delaying recurrences of bipolar disorder; however, to date their effects on life functioning have been given little attention. In a randomized trial, the authors examined the impact of intensive psychosocial treatment plus pharmacotherapy on the functional outcomes of patients with bipolar disorder over the 9 months following a depressive episode. Method: Participants were 152 depressed outpatients with bipolar I or bipolar 11 disorder in the multisite Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. All patients received pharmacotherapy. Eightyfour patients were randomly assigned to intensive psychosocial intervention (30 sessions over 9 months of interpersonal and social rhythm therapy, cognitive behavior therapy [CBT], or family-focused therapy), and 68 patients were randomly assigned to collaborative care (a 3-session psychoeducational treatment). Independent evaluators rated the four subscales of the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) (relationships, satisfaction with activities, work/role functioning, and recreational activities) through structured interviews given at baseline and every 3 months over a 9-month period. Results: Patients in intensive psychotherapy had better total functioning, relationship functioning, and life satisfaction scores over 9 months than patients in collaborative care, even after pretreatment functioning and concurrent depression scores were covaried. No effects of psychosocial intervention were observed on work/role functioning or recreation scores during this 9-month period. Conclusions: Intensive psychosocial treatment enhances relationship functioning and life satisfaction among patients with bipolar disorder. Alternate interventions focused on the specific cognitive deficits of individuals with bipolar disorder may be necessary to enhance vocational functioning after a depressive episode. C1 Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Pittsburgh, Grad Sch Publ & Int Affairs, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Community Care Behav Hlth Org, Pittsburgh, PA USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Baylor Coll Med, Menninger Dept Psychiat, Houston, TX 77030 USA. VA, VISN 16 MIRECC, Houston, TX USA. Univ Massachusetts, Sch Med, Ctr Psychopharmacol Res & Treatment, Worcester, MA USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. RP Miklowitz, DJ (reprint author), Univ Colorado, Dept Psychol, Muezinger Bldg, Boulder, CO 80309 USA. EM miklow@psych.colorado.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Ostacher, Michael/0000-0003-0353-7535 FU NIMH NIH HHS [MH43931, MH29618, MH55101, N01 MH080001, N01MH80001, R01 MH029618, R37 MH029618] NR 31 TC 125 Z9 127 U1 2 U2 19 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2007 VL 164 IS 9 BP 1340 EP 1347 DI 10.1176/appi.apj.2007.07020311 PG 8 WC Psychiatry SC Psychiatry GA 207QQ UT WOS:000249266600012 PM 17728418 ER PT J AU Goldberg, JF Perlis, RH Ghaerni, SN Calabrese, JR Bowden, CL Wisniewski, S Miklowitz, DJ Sachs, GS Thase, ME AF Goldberg, Joseph F. Perlis, Roy H. Ghaerni, S. Nassir Calabrese, Joseph R. Bowden, Charles L. Wisniewski, Stephen Miklowitz, David J. Sachs, Gary S. Thase, Michael E. TI Adjunctive antidepressant use and symptomatic recovery among bipolar depressed patients with concomitant manic symptoms: Findings from the STEP-BD SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-16, 2004 CL San Juan, PR SP Vanderbilt Univ, Sch Med, Dept Psychiat, Amer Coll Neuropsychopharmacol ID TREATMENT ENHANCEMENT PROGRAM; INTER-EPISODE STABILITY; MIXED MANIA; DYSPHORIC MANIA; SUICIDAL IDEATION; DOUBLE-BLIND; FOLLOW-UP; DISORDER; HYPOMANIA; STATES AB Objective: Practice guidelines have advised against treating patients with antidepressants during bipolar mixed states or dysphoric manias. However, few studies have examined the outcomes of patients with co-occurring manic and depressive symptoms who are treated with antidepressants plus mood stabilizing drugs. Method: The authors compared outcomes in patients with bipolar disorder who received a mood stabilizing agent with versus without an antidepressant for a bipolar depressive episode accompanied by >= 2 concurrent manic symptoms. The 335 participants were drawn from the first 2,000 enrollees in the National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Kaplan-Meier survival curves and Cox regression models were used to compare time to recovery. General linear models examined the relationship between antidepressant use or mania symptom load at the study entry and mania or depression symptom severity at the 3-month follow-up. Results: Adjunctive antidepressant use was associated with significantly higher mania symptom severity at the 3-month follow-up. The probability of recovery at 3 months was lower among patients with higher baseline depression severity. Antidepressant use neither hastened nor prolonged time to recovery once potential confounding factors were covaried in a Cox regression model. Conclusions: in bipolar depression accompanied by manic symptoms, antidepressants do not hasten time to recovery relative to treatment with mood stabilizers alone, and treatment with antidepressants may lead to greater manic symptom severity. These findings are consistent with those from the STEP-BD randomized trial for pure bipolar depression, in which adjunctive antidepressants did not yield higher recovery rates than did mood stabilizer monotherapy. C1 Silver Hill Hosp, Affect Disorders Program, New Canaan, CO USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Bipolar Disorder Res Program, Atlanta, GA USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Dept Psychiat, Cleveland, OH 44106 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Univ Colorado, Dept Psychiat, Boulder, CO 80309 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Goldberg, JF (reprint author), 128 E Ave, Norwalk, CT 06851 USA. RI Ghaemi, Nassir/J-4934-2013; OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [K-23 MH01936, N01MH80001] NR 37 TC 119 Z9 120 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2007 VL 164 IS 9 BP 1348 EP 1355 DI 10.1176/appi.ajp.2007.05122032 PG 8 WC Psychiatry SC Psychiatry GA 207QQ UT WOS:000249266600013 PM 17728419 ER PT J AU Bitondo, C Goodwin, JS Pickens-Pace, S Burnett, J Kelly, PA AF Bitondo, Carmel Goodwin, James S. Pickens-Pace, Sabrina Burnett, Jason Kelly, P. Adam TI Self-neglect among the elderly: A model based on more than 500 patients seen by a geriatric medicine team SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID EXECUTIVE CONTROL; FUNCTIONAL STATUS; FREEDOM HOUSE; OLDER-ADULTS; COMMUNITY; SERVICE; ASSOCIATION; MORTALITY; BREAKDOWN; STRESS AB Objectives. We sought to identify the functional, cognitive, and social factors associated with self-neglect among the elderly to aid the development of etiologic models to guide future research. Methods. A cross-sectional chart review was conducted at Baylor College of Medicine Geriatrics Clinic in Houston, Tex. Patients were assessed using standardized comprehensive geriatric assessment tools. Results. Data analysis was performed using the charts of 538 patients; the average patient age was 75.6 years, and 70% were women. Further analysis in 460 persons aged 65 years and older showed that 50% had abnormal Mini Mental State Examination scores, 15% had abnormal Geriatric Depression Scale scores, 76.3% had abnormal physical performance test scores, and 95% had moderate-to-poor social support per the Duke Social Support Index. Patients had a range of illnesses; 46.4% were taking no medications. Conclusions. A model of self-neglect was developed wherein executive clyscontrol leads to functional impairment in the setting of inadequate medical and social support. Future studies should aim to provide empirical evidence that validates this model as a framework for self-neglect. If validated, this model will impart a better understanding of the pathways to self-neglect and provide clinicians and public service workers with more effective prevention and intervention strategies. C1 [Bitondo, Carmel; Pickens-Pace, Sabrina; Burnett, Jason] Baylor Univ, Coll Med, Houston, TX 77030 USA. [Bitondo, Carmel; Pickens-Pace, Sabrina; Burnett, Jason] Harris Cty Hosp Dist, Houston, TX USA. [Goodwin, James S.] Univ Texas Galveston, Med Branch, Galveston, TX 77550 USA. [Kelly, P. Adam] Baylor Coll Med, Houston, TX 77030 USA. [Kelly, P. Adam] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Bitondo, C (reprint author), Univ Texas Houston, Hlth Sci Ctr, 6431 Fannin,Suite 4-200, Houston, TX 77030 USA. EM carmel.h.dyer@uth.tmc.edu FU NCRR NIH HHS [P20 RR020626, P20RR20626] NR 29 TC 8 Z9 11 U1 1 U2 9 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2007 VL 97 IS 9 BP 1671 EP 1676 DI 10.2105/AJPH.2006.097113 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297WM UT WOS:000255648100031 PM 17666694 ER PT J AU Skinner, ML Schlosser, RJ Lathers, D Neal, JG Woodworth, BA Hall, J Newton, DA Baatz, JE AF Skinner, Margaret L. Schlosser, Rodney J. Lathers, Deanne Neal, Jeffrey G. Woodworth, Bradford A. Hall, Jeffrey Newton, Danforth A. Baatz, John E. TI Innate and adaptive mediators in cystic fibrosis and allergic fungal rhinosinusitis SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article; Proceedings Paper CT Combined Otolaryngology Spring Meeting CY MAY 19-22, 2006 CL Chicago, IL DE adaptive immunity; AFRS; allergic fungal smusitis; cystic fibrosis; innate immunity; rhinosinusitis; surfactant ID SURFACTANT PROTEIN-D; ASPERGILLUS-FUMIGATUS; ALVEOLAR MACROPHAGES; SP-A; PHAGOCYTOSIS; INFLAMMATION; BACTERIA; ASTHMA AB Background: Surfactant-associated proteins (SP) A and D are both innate immunity mediators and produced in normal and diseased sinus mucosa. Cystic fibrosis (CF) is associated with Th1 adaptive inflammation whereas allergic fungal rhinosinusitis (AFRS) is associated with Th2 adaptive inflammation. The purpose of this study is to show and quantify the presence of SP A, SP D, tumor necrosis factor (TNF) alpha, (a Th1 marker), and eotaxin (a Th2 marker) in normal and diseased sinus mucosa. Methods: Intraoperative sinus mucosal biopsy specimens from human volunteers were obtained during endoscopic sinus surgery for CF (n = 4), AFRS (n = 10), and normal controls (CTLs; n = 4). Specimens were evaluated for presence and quantity of SPA, SP D, and TNF-alpha using Western blot with semiquantitative immunoblot analysis. Eotaxin was quantified using ELISA immunoassay. Results were standardized and reported as picograms of mediator per microgram of total protein. Results: SPA, SP D, and TNF-alpha levels in CF tissue extracts were 2-10 times higher than levels in AFRS tissue (with SP D and TNF-alpha reaching statistical significance) but CF tissue was not significantly higher than CTL tissue. SP A, SP D, and TNF-alpha were not significantly elevated in AFRS. Eotaxin showed elevated levels in CF and AFRS when compared with CTLs (p = 0.03 and 0.003, respectively). Conclusion: SP D and TNF-alpha are significantly increased in CF compared with AFRS, suggesting activation of both innate immunity and Th1-mediated inflammation and potential correlation between SPs and downstream adaptive immune responses. C1 Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA. Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Hosp Med Ctr, Res Serv 151, Charleston, SC USA. Med Univ S Carolina, Dept Pediat, Div Pulmonol, Charleston, SC 29425 USA. RP Skinner, ML (reprint author), Childrens Hosp, Dept Otolaryngol & Commun Enhancement, 300 Longwood Ave LO367, Boston, MA 02115 USA. EM margaret.skinner@childrens.harvard.edu OI Baatz, John/0000-0001-5870-1000 NR 17 TC 9 Z9 9 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD SEP-OCT PY 2007 VL 21 IS 5 BP 538 EP 541 DI 10.2500/ajr.2007.21.3070 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 228ZB UT WOS:000250770000003 PM 17999785 ER PT J AU Cohen, AN Wang, MB AF Cohen, Alen N. Wang, Marilene B. TI Minitrephination as an adjunctive measure in the endoscopic management of complex frontal sinus disease SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article; Proceedings Paper CT Meeting of the the Middle-Section-of-the-Triological-Society CY FEB 02-05, 2006 CL San Diego, CA SP Triol Soc, Middle Sect DE allergic fungal sinusitis; chronic sinusitis; endoscopic sinus surgery; frontal recess; frontal sinus; frontal sinusitis; minimally invasive sinus surgery; minitrephination; mucoceles; trephine ID SURGERY; TREPHINATION; MUCOCELES AB Background: Frontal sinus disease and its surgical management continues to remain an area of controversy among rhinologists. This is evidenced by the multitude of surgical procedures, both external and endoscopic, that have been developed in its management. This study was performed to evaluate the safety and efficacy of frontal sinus minitrephination in combination, with endoscopic frontal sinus exploration for the management of complex frontal sinus disease. Methods: A retrospective chart review identified 13 patients treated with minitrephination, in conjunction with endoscopic frontal sinus exploration, at the University of California at Los Angeles Medical Center or West Los Angeles VA Medical Center from July 2004 to October 2005. Results: Thirteen patients with diagnoses of chronic sinusitis (n = 10), nasal polyposis (n = 7),frontal mucocele (n = 4), allergic fungal sinusitis (n = 3), and inverting papilloma (n = 1) underwent either unilateral (n = 9) or bilateral (n = 4) minitrephination during primary or revision functional endoscopic sinus surgery. Median follow-up was 14.2 months. There were no complications attributed to the procedure, and all patients had improvement of their sinus symptoms and displayed no evidence of recurrence of their frontal sinus disease at last follow-up. Conclusion: Minitrephination is a safe and effective adjunct in the management of complex frontal sinus disease, as it allows identification of the frontal recess and vigorous irrigation of the sinus contents. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, Los Angeles, CA 90095 USA. VA Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. RP Wang, MB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, CHS 62-132,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM inbwang@ucla.edu NR 22 TC 10 Z9 10 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD SEP-OCT PY 2007 VL 21 IS 5 BP 629 EP 636 DI 10.2500/ajr.2007.21.3083 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 228ZB UT WOS:000250770000022 PM 17999804 ER PT J AU Papannagari, R DeFrate, LE Nha, KW Moses, JM Moussa, M Gill, TJ Li, G AF Papannagari, Ramprasad DeFrate, Louis E. Nha, Kyung W. Moses, Jeremy M. Moussa, Mohamed Gill, Thomas J. Li, Guoan TI Function of posterior cruciate ligament bundles during in vivo knee flexion SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the AOSSM CY JUN 30-JUL 03, 2002 CL Orlando, FL SP AOSSM DE posterior cruciate ligament; in vivo kinematics; posterior cruciate ligament reconstruction; double-bundle reconstruction ID SIMULATED MUSCLE LOADS; SITU FORCES; TIBIOFEMORAL JOINT; CARTILAGE CONTACT; SINGLE-BUNDLE; KINEMATICS; RECONSTRUCTION; ANTERIOR; DEFICIENCY; TENDON AB Background: The biomechanical functions of the anterolateral and posteromedial bundles of the posterior cruciate ligament over the range of flexion of the knee joint remain unclear. Hypothesis: The posterior cruciate ligament bundles have minimal length at low flexion angles and maximal length at high flexion angles. Study Design: Descriptive laboratory study. Methods: Seven knees from normal, healthy subjects were scanned with magnetic resonance, and 3-dimensional models of the femur, tibia, and posterior cruciate ligament attachment sites were created. The lines connecting the centroids of the corresponding bundle attachment sites on the femur and tibia represented the anterolateral and posteromedial bundles of the posterior cruciate ligament. Each knee was imaged during weightbearing flexion (from 0 degrees to maximal flexion) using a dual-orthogonal fluoroscopic system. The length, elevation, deviation, and twist of the posterior cruciate ligament bundles were measured as a function of flexion. Results: The lengths of the anterolateral and posteromedial bundles increased with flexion from 0 degrees to 120 degrees and decreased beyond 120 degrees of flexion. The posteromedial bundle had a lower elevation angle than the anterolateral bundle beyond 60 degrees of flexion. The anterolateral bundle had a larger deviation angle than the posteromedial bundle beyond 751 of flexion. The femoral attachment of the posterior cruciate ligament twisted externally with increasing flexion and reached a maximum of 86.4 degrees 14.7 degrees at 135 degrees of flexion (P < .05). Conclusion: These data suggest that there is no reciprocal function of the bundles with flexion, which is contrary to previous findings. The orientation of the anterolateral and posteromedial bundles suggests that at high flexion, the anterolateral bundle might play an important role in constraining the mediolateral translation, whereas the posteromedial bundle might play an important role in constraining the anteroposterior translation of the tibia. Clinical Relevance: These data provide a better understanding of the biornechanical function of the posterior cruciate ligament bundles and may help to improve the design of the 2-bundle reconstruction techniques of the ruptured posterior cruciate ligament. C1 Massachusetts Gen Hosp, Bioengn Lab, Boston, MA 02114 USA. Duke Univ, Orthopaed Res Labs, Durham, NC USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02115 USA. Inje Univ, Dept Orthopaed Surg, Ilsan, South Korea. Ilsanpaik Hosp, Ilsan, South Korea. RP Li, G (reprint author), Massachusetts Gen Hosp, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU NIAMS NIH HHS [R01 AR 052408] NR 31 TC 43 Z9 50 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD SEP PY 2007 VL 35 IS 9 BP 1507 EP 1512 DI 10.1177/0363546507300061 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 205XY UT WOS:000249149700012 PM 17376856 ER PT J AU Suh, N Liapis, H Misdraji, J Brunt, EM Wang, HL AF Suh, Namsoo Liapis, Helen Misdraji, Joseph Brunt, Elizabeth M. Wang, Hanlin L. TI Epstein-Barr virus hepatitis: Diagnostic value of in situ hybridization, polymerase chain reaction, and immunohistochemistry on liver biopsy from immunocompetent patients SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Epstein-Barr virus hepatitis; polymerase chain reaction; in situ hybridization; immunohistochemistry; liver biopsy ID T-CELL LYMPHOMA; AUTOIMMUNE HEPATITIS; GAMMA-DELTA; INFECTION; INDIVIDUALS; SERIES AB Epstein-Barr virus (EBV) hepatitis is an uncommon, almost always self-limited disease in immunocompetent patients. Accurate diagnosis is imperative for appropriate clinical management. The aim of this study was to compare 3 available methods for EBV detection on routinely processed liver biopsies to determine their effectiveness in aiding the diagnosis. In 6 of the 8 cases of EBV hepatitis, EBV was detected by both polymerase chain reaction (PCR) for EBV DNA and in situ hybridization (ISH) for EBV early RNA (EBER). EBV was detected by PCR only in I case, and by ISH only in another. EBER-positive cells detected by ISH were typically few and individually distributed in the portal tracts and sinusoids. Immunohistochemical staining for EBV latent membrane proteins was negative in all 8 cases. Five cases of chronic hepatitis C used as negative controls were negative by all 3 detection methods for EBV. These data indicate that PCR and ISH are equally sensitive in detecting EBV in routinely processed liver biopsies. The ready implementation of ISH in pathology laboratories makes it a useful ancillary tool in confirming the diagnosis of EBV hepatitis in equivocal cases. However, EBER-positive cells can be sparse and easily overlooked. Immunohistochemistry for EBV latent membrane proteins apparently has no utility in the diagnosis of EBV hepatitis. C1 Washington Univ, Sch Med, Dept Pathol & Immunol, Lauren V Ackerman Lab Surg Pathol, St Louis, MO 63110 USA. St Louis Univ, Sch Med, Dept Pathol, St Louis, MO 63103 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Wang, HL (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, Lauren V Ackerman Lab Surg Pathol, Campus Box 8118,660 S Euclid Ave, St Louis, MO 63110 USA. EM hwang@path.wustl.edu NR 25 TC 16 Z9 16 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2007 VL 31 IS 9 BP 1403 EP 1409 DI 10.1097/PAS.0b013e31802ffdd5 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 206FW UT WOS:000249170300013 PM 17721196 ER PT J AU Seliem, RM Griffith, RC Harris, NL Beheshti, J Schiffman, FJ Longtine, J Kutok, J Ferry, JA AF Seliem, Rania M. Griffith, Rogers C. Harris, Nancy L. Beheshti, Javad Schiffman, Fred J. Longtine, Janina Kutok, Jeffery Ferry, Judith A. TI HHV-8+, EBV+ multicentric plasmablastic microlymphoma in an HIV+ man: The spectrum of HHV-8+lymphoproliferative disorders expands SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE human herpesvirus-8 (HHV-8); Kaposi sarcoma-associated herpes virus (KSHV); germinotropic; lymphoma; multicentric Castleman disease; HIV ID SARCOMA-ASSOCIATED HERPESVIRUS; PRIMARY EFFUSION LYMPHOMA; KAPOSIS-SARCOMA; CASTLEMAN-DISEASE; DNA-SEQUENCES; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; INFECTION; VARIANT; IMMUNOGLOBULIN; ENTITY AB Human herpesvirus-8 (HHV-8) is associated with several distinct lymphoproliferative disorders: primary effusion lymphoma, multicentric Castleman disease (MCD), MCD-associated plasmablastic lymphoma and HHV-8+, Epstein-Barr virus (EBV) + germinotropic lymphoproliferative disorder. We report the case of a human immunodeficiency virus (HIV) + mate with fever, generalized lymphadenopathy, and splenomegaly. Two peripheral lymph nodes were excised and showed features of MCD and a prominent proliferation of HHV-8+, EBV+, CD20(-/+), CD138(-), MUM1+, lambda dim+, Ig heavy chain plasmablasts and immunoblasts replacing some follicles. Subsequently, a splenectomy and biopsy of retroperitoneal lymph nodes were performed; the retroperitoneal and splenic hilar lymph nodes showed changes similar to those in the peripheral lymph nodes while the markedly enlarged spleen showed replacement of occasional white pulp by the HHV-8 +, EBV+ large cells. The histologic features and coinfection by EBV and HHV-8 suggested a diagnosis of HHV-8+ germinotropic lymphoproliferative disorder. However, the occurrence in an HIV+ individual, the background of MCD, the widespread anatomic distribution and the aggressive clinical course tended to exclude germinotropic lymphoproliferative disorder, and to favor multifocal plasmablastic microlymphoma. The patient died shortly after surgery; postmortem examination showed progression to overt lymphoma. The marrow showed extensive hemophagocytosis, consistent with development of a hemophagocytic syndrome. This unique case has clinical features compatible with a MCD-associated plasmablastic lymphoproliferative disorder, with pathologic features intermediate between HHV-8 + plasmablastic microlymphoma, and HHV-8 + germinotropic lymph oproliferative disorder, although in contrast to both of these, in our case, light chain expression was dim and heavy chain was not detected. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Miriam Hosp, Dept Pathol, Providence, RI 02906 USA. Miriam Hosp, Dept Med, Providence, RI 02906 USA. Brown Univ, Sch Med, Rhode Isl Hosp, Providence, RI 02912 USA. RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, Fruit St, Boston, MA 02114 USA. EM jferry@partners.org NR 23 TC 31 Z9 31 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2007 VL 31 IS 9 BP 1439 EP 1445 DI 10.1097/PAS.0b013e31804d43d8 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 206FW UT WOS:000249170300018 PM 17721201 ER PT J AU Barcia, RN Dana, MR Kazlauskas, A AF Barcia, R. N. Dana, M. R. Kazlauskas, A. TI Corneal graft rejection is accompanied by apoptosis of the endothelium and is prevented by gene therapy with Bcl-xL SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE allograft rejection; apoptosis; bcl-xL; corneal transplantation; lentiviral gene therapy ID BACULOVIRUS P35 PROTEIN; ALLOGRAFT-REJECTION; PENETRATING KERATOPLASTY; T-LYMPHOCYTES; CELL DENSITY; SURVIVAL; MICE; TRANSPLANTATION; FAMILY; DEATH AB Corneal transplants normally enjoy a high percentage of survival, mainly because the eye is an immune-privileged site. When allograft failure occurs, it is most commonly due to rejection, an immune-mediated reaction that targets the corneal endothelium. While the exact mechanism by which the endothelium is targeted is still unknown, we postulate that corneal endothelial cell loss during allograft failure is mediated by apoptosis. Furthermore, because corneal endothelial cells do not normally regenerate, we hypothesize that suppressing apoptosis in the graft endothelium will promote transplant survival. In a murine model of transplantation, TUNEL staining and confocal microscopy showed apoptosis of the graft endothelium occurring in rejecting corneas as early as 2 weeks post-transplantation. We found that bcl-xL protected cultured corneal endothelial cells from apoptosis and that lentiviral delivery of bcl-xL to the corneal endothelium of donor corneas significantly improved the survival of allografts. These studies suggest a novel approach to improve corneal allograft survival by preventing apoptosis of the endothelium. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kazlauskas, A (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM ak@vision.eri.harvard.edu FU NEI NIH HHS [R01-EY12963, R21 EY015738] NR 38 TC 40 Z9 43 U1 0 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2007 VL 7 IS 9 BP 2082 EP 2089 DI 10.1111/j.1600-6143.2007.01897.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 199AE UT WOS:000248667800006 PM 17614980 ER PT J AU Kawahara, T Rodriguez-Barbosa, JI Zhao, Y Zhao, G Sykes, M AF Kawahara, T. Rodriguez-Barbosa, J.-I. Zhao, Y. Zhao, G. Sykes, M. TI Global unresponsiveness as a mechanism of natural killer cell tolerance in mixed xenogeneic chimeras SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE mixed chimerism; natural killer; tolerance; transplantation; xenograft; xenotransplantation ID MHC-CLASS-I; NONMYELOABLATIVE CONDITIONING REGIMEN; DEFICIENT HEMATOPOIETIC-CELLS; NONLETHAL PREPARATIVE REGIMEN; PORCINE ENDOTHELIAL-CELLS; HUMAN NK CYTOTOXICITY; BONE-MARROW CHIMERAS; XENOGRAFT REJECTION; NONHUMAN-PRIMATES; DENDRITIC CELLS AB Mixed xenogeneic chimerism induces T- and B-cell tolerance in mice receiving T-cell-depleted rat bone marrow cells (BMC) following nonmyeloablative conditioning that includes alpha beta and gamma delta T cell and Natural killer (NK) cell-depleting mAbs. NK-cell depletion is essential to permit marrow engraftment, but NK-cell tolerance has not been previously assessed in mixed xenogeneic chimeras. We assessed NK-cell tolerance in rat -> mouse mixed xenogeneic chimeras using in vivo I-125-5iodo-2-deoxyuridine assays. Additional rapid marrow rejection mechanisms resulted in a requirement for 10-fold more rat than ss 2 microglobulin knockout (ss 2M(-/-)) (MHC class I-deficient) mouse BMC to achieve engraftment in NK-cell-depleted mice. Both 12-week mixed xenogeneic chimeras and conditioned controls showed reduced resistance to engraftment of ss 2M(-/-) mouse and rat BMC. While conditioned control mice recovered NK-cell-mediated resistance to ss 2M(-/-) and rat BMC by 16 weeks, mixed chimeras lacked resistance to either, similar to NK-cell-deficient Ly49A transgenic mice. Thus, global NK-cell unresponsiveness is induced by mixed xenogeneic chimerism. Our data suggest that NK-cell anergy is induced by interactions with xenogeneic hematopoietic cells that express activating but not inhibitory ligands for recipient NK cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. EM megan.sykes@tbrc.mgh.harvard.edu RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011; OI Rodriguez-Barbosa, Jose-Ignacio/0000-0001-7427-5654 FU NHLBI NIH HHS [R01 HL49915, P01 HL18646]; NIAID NIH HHS [P01 AI45897] NR 50 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2007 VL 7 IS 9 BP 2090 EP 2097 DI 10.1111/j.1600-6143.2007.01905.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 199AE UT WOS:000248667800007 PM 17640313 ER PT J AU Olson, DP Day, CL Magula, NP Sahid, F Moosa, MYS AF Olson, Douglas P. Day, Cheryl L. Magula, Nombulelo P. Sahid, Faieza Moosa, Mahomed-Yunus S. TI Case report: Cutaneous extensively drug-resistant tuberculosis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article AB A 48-year-old immunocompetent man without known exposure to tuberculosis had a > 10-year history of recurrent skin lesions. Cutaneous tuberculosis without any current or past history of pulmonary tuberculosis was diagnosed. Culture of biopsy specimens showed the organism to be resistant to multiple first-line and second-line agents. The patient had a broad, vigorous CD4-specific immune response against multiple tuberculosis antigens. This case is the first report of cutaneous extensively drug-resistant tuberculosis. C1 Univ KwaZulu Natal, Dept Infect Dis, Div Med, Durban, South Africa. Univ KwaZulu Natal, HIV Pathogenesis Programme, Durban, South Africa. George Washington Univ, Sch Med, Washington, DC USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Olson, DP (reprint author), Yale Univ, Sch Med, 26131 Town Walk Dr, Hamden, CT 06518 USA. EM douglas.olson@yale.edu RI Day, Cheryl/J-9844-2012 NR 14 TC 2 Z9 3 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 2007 VL 77 IS 3 BP 551 EP 554 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 208IE UT WOS:000249312200027 PM 17827377 ER PT J AU Chumnanvej, S Wood, MJ MacGillivray, TE Melo, MFV AF Chumnanvej, Siriluk Wood, Malissa J. MacGillivray, Thomas E. Melo, Marcos F. Vidal TI Perioperative echocardiographic examination for ventricular assist device implantation SO ANESTHESIA AND ANALGESIA LA English DT Review ID MECHANICAL CIRCULATORY SUPPORT; PATENT FORAMEN OVALE; IDIOPATHIC DILATED CARDIOMYOPATHY; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; FUNCTIONAL MITRAL REGURGITATION; ANESTHESIOLOGISTS TASK-FORCE; OUTFLOW TRACT OBSTRUCTION; NATIVE AORTIC-VALVE; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; HEART-FAILURE AB Ventricular assist devices (VADs) are systems for mechanical circulatory support of the patient with severe heart failure. Perioperative transesophageal echocardiography is a major component of patient management, and important for surgical and anesthetic decision making. In this review we present the rationale and available data for a comprehensive echocardiographic assessment of patients receiving a VAD. In addition to the standard examination, device-specific pre-, intra-, and postoperative considerations are essential to the echocardiographic evaluation. These include: (a) the pre-VAD insertion examination of the heart and large vessels to exclude significant aortic regurgitation, tricuspid. regurgitation, mitral stenosis, patent foramen ovale, or other cardiac abnormality that could lead to right-to-left shunt after left VAD placement, intracardiac thrombi, ventricular scars, pulmonic regurgitation, pulmonary hypertension, pulmonary embolism, and atherosclerotic disease in the ascending aorta; and to assess right ventricular function; and (b) the post-VAD insertion examination of the device and reassessment of the heart and large vessels. The examination of the device aims to confirm completeness of device and heart deairing, cannulas alignment and patency, and competency of device valves using two-dimensional, and color, continuous and pulsed wave Doppler modalities. The goal for the heart examination after implantation should be to exclude aortic regurgitation, or an uncovered right-to-left shunt; and to assess right ventricular function, left ventricular unloading, and the effect of device settings on global heart function. The variety of VAD models with different basic and operation principles requires specific echocardiographic assessment targeted to the characteristics of the implanted device. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM mvidatmelo@partners.org OI Chumnanvej, Sorayouth/0000-0002-5099-0247 NR 153 TC 78 Z9 81 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 2007 VL 105 IS 3 BP 583 EP 601 DI 10.1213/01.ane.0000278088.22952.82 PG 19 WC Anesthesiology SC Anesthesiology GA 202SS UT WOS:000248924400004 PM 17717209 ER PT J AU Zapol, WM AF Zapol, Warren M. TI Marcos F. Vidal Melo, MD, Ph.D., recipient of the 2007 presidential scholar award SO ANESTHESIOLOGY LA English DT Biographical-Item C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM wzapol@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2007 VL 107 IS 3 BP 383 EP 385 DI 10.1097/01.anes.0000279486.77183.65 PG 3 WC Anesthesiology SC Anesthesiology GA 208CK UT WOS:000249297200005 ER PT J AU Metlay, JP Camargo, CA MacKenzie, T McCulloch, C Maselli, J Levin, SK Kersey, A Gonzales, R AF Metlay, Joshua P. Camargo, Carlos A. MacKenzie, Thomas McCulloch, Charles Maselli, Judith Levin, Sara K. Kersey, Ayanna Gonzales, Ralph CA IMPAACT Invest TI Cluster-randomized trial to improve antibiotic use for adults with acute respiratory infections treated in emergency departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY, 2006 CL San Francisco, CA SP Soc Acad Emergency Med ID UNCOMPLICATED ACUTE BRONCHITIS; TRACT INFECTIONS; UNITED-STATES; INTERVENTION; TRENDS; PRINCIPLES; COMMUNITY; IMPACT; PHYSICIANS; RESISTANCE AB Study objective: We evaluate the effectiveness of an educational program in hospital emergency departments (EDs) targeting reduction in antibiotic overuse for acute respiratory tract infections. Methods: Sixteen hospitals participated in the cluster randomized trial, selecting a Veterans Administration (VA) and non-VA hospital within each of 8 metropolitan regions. Intervention sites received performance feedback, clinician education, and patient educational materials, including an interactive computer kiosk located in the waiting room. Medical records were reviewed at each site during the baseline year 1 and intervention year 2. The primary measure of effect was the percentage of visits for upper respiratory tract infections and acute bronchitis that were treated with antibiotics. Secondary outcomes, including return visits and visit satisfaction, were assessed by follow-up telephone interviews of patients. Alternating logistic regression models were used to adjust for baseline treatment rates, case mix differences, and provider characteristics. Results: The adjusted antibiotic prescription level for upper respiratory tract infection/acute bronchitis visits was 47% for control sites and 52% for intervention sites in year 1. Antibiotic prescriptions at control sites increased by 0.5% between year 1 and year 2 (95% confidence interval -3% to 5%) and at intervention sites decreased by 10% (95% confidence interval -18% to -2%). There were no significant differences between control and intervention sites in the proportions of upper respiratory tract infection/bronchitis patients with return ED visits or in overall visit satisfaction. Conclusion: Multidimensional educational interventions can reduce antibiotic overuse in the treatment of patients with upper respiratory tract infections and acute bronchitis in ElDs. However, substantial antibiotic overuse persists despite this educational intervention. C1 VA Med Ctr, Ctr Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Educ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Res Therapeut, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Denver Hlth Med Ctr, Denver, CO USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Metlay, JP (reprint author), VA Med Ctr, Ctr Equity Res & Promot, Philadelphia, PA USA. EM jmetlay@cceb.med.upenn.edu FU AHRQ HHS [1 R01 HS013915] NR 25 TC 36 Z9 36 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 BP 221 EP 230 DI 10.1016/j.annemergmed.2007.03.022 PG 10 WC Emergency Medicine SC Emergency Medicine GA 206YN UT WOS:000249218900002 PM 17509729 ER PT J AU Arbelaez, C Losina, E Wright, E Millen, J Dooley, M Reichman, B Mikulinsky, R Walensky, R AF Arbelaez, C. Losina, E. Wright, E. Millen, J. Dooley, M. Reichman, B. Mikulinsky, R. Walensky, R. TI The barriers affecting health care providers' willingness to perform routine HIV testing in the emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 376 BP S118 EP S118 DI 10.1016/j.annemergmed.2007.06.315 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600378 ER PT J AU Camargo, CA Sullivan, AF Singer, AJ AF Camargo, C. A., Jr. Sullivan, A. F. Singer, A. J. TI Reassessment of emergency physician workforce needs SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Med Ctr, Stony Brook, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 284 BP S89 EP S90 DI 10.1016/j.annemergmed.2007.06.270 PG 2 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600285 ER PT J AU Chawla, N Feldman, J Moyer, P Mitchell, PM Rebholz, CM Beshansky, J AF Chawla, N. Feldman, J. Moyer, P. Mitchell, P. M. Rebholz, C. M. Beshansky, J. TI Reviewer determination of paramedic performance in recognition of ST segment elevation acute myocardial infarction (STEMI): Performance measurement depends on the reviewer SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 169 BP S54 EP S54 DI 10.1016/j.annemergmed.2007.06.203 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600169 ER PT J AU Cushing, TA Goldstein, JN Wendell, L Schwab, K Smith, EE Greenberg, SM Rosand, J AF Cushing, T. A. Goldstein, J. N. Wendell, L. Schwab, K. Smith, E. E. Greenberg, S. M. Rosand, J. TI Hematoma shape is not significantly influenced by warfarin use in patients with intracerebral hemorrhage SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012; Goldstein, Joshua/H-8953-2016 OI Smith, Eric/0000-0003-3956-1668; NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 103 BP S33 EP S33 DI 10.1016/j.annemergmed.2007.06.135 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600103 ER PT J AU Delaney, KE Clark, S Ginde, AA Camargo, CA AF Delaney, K. E. Clark, S. Ginde, A. A. Camargo, C. A., Jr. TI National study of numeric literacy among emergency department patients with acute asthma SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. New York Presbyterian Hosp, New York, NY USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 140 BP S45 EP S45 DI 10.1016/j.annemergmed.2007.06.173 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600140 ER PT J AU Egan, DJ Pelletier, AJ Hooper, DC Camargo, CA AF Egan, D. J. Pelletier, A. J. Hooper, D. C. Camargo, C. A., Jr. TI Trends in US emergency department visits for skin and soft tissue infections in the age of methicillin-resistant Staphylococcus aureus, 1993-2004 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 St Vincents Hosp Manhattan, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 183 BP S58 EP S58 DI 10.1016/j.annemergmed.2007.06.335 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600183 ER PT J AU Fix, ML Weissman, JS Park, E Hevelone, N Shapiro, J AF Fix, M. L. Weissman, J. S. Park, E. Hevelone, N. Shapiro, J. TI Attitudes and barriers to physicians receiving assistance for personal and professional struggles: A survey of emergency physicians, anesthesiologists, and surgeons SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 130 BP S42 EP S42 DI 10.1016/j.annemergmed.2007.06.163 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600130 ER PT J AU Ginde, AA Delaney, KE Carnargo, CA AF Ginde, A. A. Delaney, K. E. Carnargo, C. A., Jr. TI Implementation of hemoglobin A1c testing to identify undiagnosed and uncontrolled diabetes in the emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 407 BP S128 EP S128 DI 10.1016/j.annemergmed.2007.06.456 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600410 ER PT J AU Ginde, AA Blanc, PG Lieberman, RM Camargo, CA AF Ginde, A. A. Blanc, P. G. Lieberman, R. M. Camargo, C. A., Jr. TI Validation of coding algorithm to improve identification of hypoglycemia visits SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 142 BP S46 EP S46 DI 10.1016/j.annemergmed.2007.06.175 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600142 ER PT J AU Lovett, P Newman-Toker, DE Stanton, V Hsieh, Y Camargo, CA Edlow, JA Goldstein, JN Abbuhl, S Lin, M Chanmugam, A Rothman, RE AF Lovett, P. Newman-Toker, D. E. Stanton, V Hsieh, Y. Camargo, C. A., Jr. Edlow, J. A. Goldstein, J. N. Abbuhl, S. Lin, M. Chanmugam, A. Rothman, R. E. TI Diagnosing dizziness in the emergency department: Physicians may rely too heavily on symptom quality. Results of a multicenter, quantitative survey SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 33 BP S11 EP S11 DI 10.1016/j.annemergmed.2007.06.064 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600034 ER PT J AU Nathanson, LA Luff, P Tracy, JA Fisher, J AF Nathanson, L. A. Luff, P. Tracy, J. A. Fisher, J. TI Patient age as predictor of resource utilization SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 70 BP S23 EP S23 DI 10.1016/j.annemergmed.2007.06.101 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600071 ER PT J AU Pallin, DJ Sullivan, AF Auerbach, BS Camargo, CA AF Pallin, D. J. Sullivan, A. F. Auerbach, B. S. Camargo, C. A., Jr. TI Information technology resources in Massachusetts EDs in 2006 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sturdy Mem Hosp, Attleboro, MA USA. RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 73 BP S24 EP S24 DI 10.1016/j.annemergmed.2007.06.105 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600074 ER PT J AU Peacock, WF Varon, J Garrison, N Ebrahimi, R Dunbar, L Pollack Jr AF Peacock, W. F. Varon, J. Garrison, N. Ebrahimi, R. Dunbar, L. Pollack, Jr. TI IV clevidipine for hypertension: Safety, efficacy, and transition to oral therapy SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Cleveland Clin, Cleveland, OH 44106 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Jackson Hosp, Montgomery, AL USA. VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 24 BP S8 EP S9 DI 10.1016/j.annemergmed.2007.06.055 PG 2 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600026 ER PT J AU Rogg, JG De Neve, J Huang, C Brown, D Jang, I Chang, Y Marill, K Parry, B Hoffmann, U Nagurney, JT AF Rogg, J. G. De Neve, J. Huang, C. Brown, D. Jang, I Chang, Y. Marill, K. Parry, B. Hoffmann, U. Nagurney, J. T. TI The triple workup for emergency department patlents with acute chest pain: How often does it occur? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Tufts Univ, Sch Med, Boston, MA 02111 USA. Univ Brussels, Brussels, Belgium. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 361 BP S112 EP S113 DI 10.1016/j.annemergmed.2007.06.422 PG 2 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600363 ER PT J AU Smulowitz, PB Brown, D Camargo, CA Wolfe, R AF Smulowitz, P. B. Brown, D. Camargo, C. A., Jr. Wolfe, R. TI Patient characteristics by source of admission: Who is affected when the ED gets crowded? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 56 BP S18 EP S19 DI 10.1016/j.annemergmed.2007.06.087 PG 2 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600057 ER PT J AU Wittels, KA Takayesu, JK Nadel, ES AF Wittels, K. A. Takayesu, J. K. Nadel, E. S. TI A two year experience of integrating simulation into an emergency medicine residency curriculum SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2007 VL 50 IS 3 SU S MA 46 BP S15 EP S15 DI 10.1016/j.annemergmed.2007.06.077 PG 1 WC Emergency Medicine SC Emergency Medicine GA 211PL UT WOS:000249535600047 ER PT J AU Lasky-Su, J Biederman, J Laird, N Tsuang, M Doyle, AE Smoller, JW Lange, C Faraone, SV AF Lasky-Su, J. Biederman, J. Laird, N. Tsuang, M. Doyle, A. E. Smoller, J. W. Lange, C. Faraone, S. V. TI Evidence for an association of the dopamine D5 receptor gene on age at onset of attention deficit hyperactivity disorder SO ANNALS OF HUMAN GENETICS LA English DT Article DE ADHD; DRD5; age at onset; family-based association; PBAT; candidate gene ID DEFICIT/HYPERACTIVITY-DISORDER; LEARNING-DISABILITIES; FAMILY; CHILDREN; TESTS; ADHD; TRANSMISSION; TRANSPORTER; RELIABILITY; POPULATION AB The purpose of this study was to determine whether the single nucleotide polymorphisms (SNPs) within candidate genes for attention deficit hyperactivity disorder (ADHD) are associated with the age at onset for ADHD. One hundred and forty-three SNPs were genotyped across five candidate genes (DRD5, SLC6A3, HTR1B, SNAP25, DRD4) for ADHD in 229 families with at least one affected offspring. SNPs with the highest estimated power to detect an association with age at onset were selected for each candidate gene, using a power-based screening procedure that does not compromise the nominal significance level. A time-to-onset analysis for family-based samples was performed on these SNPs to determine if an association exists with age at onset for ADHD. Seven consecutive SNPs surrounding the D5 dopamine receptor gene (DRD5), were associated with the age at onset for ADHD; FDR adjusted q-values ranged from 0.008 to 0.023. This analysis indicates that individuals with the risk genotype develop ADHD earlier than individuals with any other genotype. A haplotype analysis across the 6 significant SNPs that were in linkage disequilibrium with one another, CTCATA, was also found to be significant (p-value = 0.02). We did not observe significant associations with age at onset for the other candidate loci tested. Although definitive conclusions await independent replication, these results suggest that a variant in DRD5 may affect age at onset for ADHD. C1 SUNY Upstate Med Univ, Dept Psychiat, Genet Res Program, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Univ Calif San Diego, Inst Behav Genom, San Diego, CA 92103 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat, Genet Res Program, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD37999, R01HD37694]; NIMH NIH HHS [MH059532, R01MH66877, T32-MH017119] NR 54 TC 12 Z9 12 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD SEP PY 2007 VL 71 BP 648 EP 659 DI 10.1111/j.1469-1809.2007.00366.x PN 5 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 191HH UT WOS:000248121700010 PM 17501935 ER PT J AU Johnson, KA Gregas, M Becker, JA Kinnecom, C Salat, DH Moran, EK Smith, EE Rosand, J Rentz, DM Klunk, WE Mathis, CA Price, JC DeKosky, ST Fischman, AJ Greenberg, SM AF Johnson, Keith A. Gregas, Matt Becker, John A. Kinnecom, Catherine Salat, David H. Moran, Erin K. Smith, Erin E. Rosand, Jonathan Rentz, Dorene M. Klunk, William E. Mathis, Chester A. Price, Julie C. DeKosky, Steven T. Fischman, Alan J. Greenberg, Steven M. TI Imaging of amyloid burden and distribution in cerebral amyloid angiopathy SO ANNALS OF NEUROLOGY LA English DT Article ID PITTSBURGH COMPOUND-B; WHITE-MATTER LESIONS; LOBAR INTRACEREBRAL HEMORRHAGE; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; CLINICAL-DIAGNOSIS; GRAPHICAL ANALYSIS; A-BETA; BRAIN; PET AB Objective: Cerebrovascular deposition of beta-amyloid (cerebral amyloid angiopathy [CAA]) is a major cause of hemorrhagic stroke and a likely contributor to vascular cognitive impairment. We evaluated positron emission tomographic imaging with the beta-amyloid-binding compound Pittsburgh Compound B (PiB) as a potential noninvasive method for detection of CAA. We hypothesized that amyloid deposition would be observed with PiB in CAA, and based on the occipital predilection of CAA pathology and associated hemorrhages, that specific PiB retention would be disproportionately greater in occipital lobes. Methods: We compared specific cortical PiB retention in 6 nondemented subjects diagnosed with probable CAA with 15 healthy control subjects and 9 patients with probable Alzheimer's disease (AD). Results: All CAA and AD subjects were PiB-positive, both by distribution volume ratio measurements and by visual inspection of positron emission tomographic images. Global cortical PiB retention was significantly increased in CAA (distribution volume ratio 1.18 +/- 0.06) relative to healthy control subjects (1.04 +/- 0.10; p = 0.0009), but was lower in CAA than in AD subjects (1.41 +/- 0.17; p = 0.002). The occipital-to-global PiB ratio, however, was significantly greater in CAA than in AD subjects (0.99 +/- 0.07 vs 0.86 +/- 0.05; p = 0.003). Interpretation: We conclude that PiB-positron emission tomography can detect cerebrovascular beta-amyloid and may serve as a method for identifying the extent of CAA in living subjects. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15260 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM sgreenberg@partners.org RI Mathis, Chester/A-8607-2009; OI Klunk, William/0000-0001-5512-0251; Smith, Eric/0000-0003-3956-1668 FU NIA NIH HHS [P50 AG00513421, R01 AG026484]; NINDS NIH HHS [T32 NS048005] NR 44 TC 258 Z9 266 U1 1 U2 16 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2007 VL 62 IS 3 BP 229 EP 234 DI 10.1002/ana.21164 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 217GS UT WOS:000249937000008 PM 17683091 ER PT J AU Zeitels, SM Blitzer, A Hillman, RE Anderson, RR AF Zeitels, Steven M. Blitzer, Andrew Hillman, Robert E. Anderson, R. Rox TI Foresight in laryngology and laryngeal surgery: A 2020 vision SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the American-Broncho-Esophagological-Association CY MAY 13-14, 2005 CL Boca Raton, FL SP Amer Broncho Esophagol Assoc DE cancer; glottis; laryngology; laryngoscopy; larynx; laser; vocal cord; vocal fold; voice ID OPTICAL COHERENCE TOMOGRAPHY; VOCAL-FOLD COLLISION; TOPICAL MITOMYCIN-C; PULSED DYE-LASER; VOICE QUALITY; LARYNGOTRACHEAL RECONSTRUCTION; ELECTROMYOGRAPHIC ACTIVITY; ENDOSCOPIC EVALUATION; GLOTTAL DYSPLASIA; BOTULINUM TOXIN AB Laryngology and laryngeal surgery have been in the vanguard of minimally invasive human procedural interventions for approximately 150 years. The natural passages through the oral cavity, nose, and pharynx have provided an accessible gateway to the larynx that has allowed for rapid translation of a variety of diagnostic and therapeutic technologies. Transoral and transcervical laryngeal surgery have been further facilitated by progressive advancements in local, topical, intravenous, and general anesthesia. With rapid developments in engineering disciplines (ie, tissue, chemical, mechanical) and voice science, there are a variety of current and near-term opportunities to advance our field. This report represents a panel at the 2005 American Broncho-Esophagological Association meeting that sought to use present perspectives, combined with cutting-edge research insights, to provide foresight into key aspects of laryngology that we believe will be developed by the year 2020. We hope that aspiring laryngeal surgeons will find elements of this discussion valuable for devising a strategic roadmap for research initiatives in laryngology and laryngeal surgery. C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Columbia Univ, New York Ctr Voice & Swallowing Disorders, Dept Clin Otolaryngol, New York, NY USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdon Sq,11th Floor, Boston, MA 02114 USA. NR 102 TC 6 Z9 6 U1 0 U2 4 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 2007 VL 116 IS 9 SU 198 BP 2 EP 16 PN 2 PG 15 WC Otorhinolaryngology SC Otorhinolaryngology GA 213TM UT WOS:000249690000001 ER PT J AU Bilimoria, KY Bentrem, DJ Ko, CY Stewart, AK Winchester, DP Talamonti, MS Sturgeon, C AF Bilimoria, Karl Y. Bentrem, David J. Ko, Clifford Y. Stewart, Andrew K. Winchester, David P. Talamonti, Mark S. Sturgeon, Cord TI Extent of surgery affects survival for papillary thyroid cancer SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 127th Annual Meeting of the American-Surgical-Association CY APR, 2007 CL Colorado Springs, CO SP Amer Surg Assoc ID DIFFERENTIATED CARCINOMA; COLORECTAL-CANCER; RADIATION-THERAPY; PROGNOSTIC INDEX; UNITED-STATES; RISK-GROUP; CHEMOTHERAPY; INFORMATION; MANAGEMENT; OUTCOMES AB Background: The extent of surgery for papillary thyroid cancers (PTC) remains controversial. Consensus guidelines have recommended total thyroidectomy for PTC >= 1 cm; however, no study has supported this recommendation based on a survival advantage. The objective of this study was to examine whether the extent of surgery affects outcomes for PTC and to determine whether a size threshold could be identified above which total thyroidectomy is associated with improved outcomes. Methods: From the National Cancer Data Base (1985-1998), 52,173 patients underwent surgery for PTC. Survival was estimated by the Kaplan-Meier method and compared using log-rank tests. Cox Proportional Hazards modeling stratified by tumor size was used to assess the impact of surgical extent on outcomes and to identify a tumor size threshold above which total thyroidectomy is associated with an improvement in recurrence and long-term survival rates. Results: Of the 52,173 patients, 43,227 (82.9%) underwent total thyroidectomy, and 8946 (17.1%) underwent lobectomy. For PTC < 1 cm extent of surgery did not impact recurrence or survival (P = 0.24, P = 0.83). For turnors >= 1 cm, lobectomy resulted in higher risk of recurrence and death (P = 0.04, P = 0.009). To minimize the influence of larger tumors, 1 to 2 cm lesions were examined separately: lobectomy again resulted in a higher risk of recurrence and death (P = 0.04, P = 0.04). Conclusions: The results of this study demonstrate that total thyroidectomy results in lower recurrence rates and improved survival for PTC >= 1.0 cm compared with lobectomy. This is the first study to demonstrate that total thyroidectomy for PTC >= 1.0 cm improves outcomes. C1 Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL USA. Amer Coll Surgeons, Chicago, IL USA. Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Evanston NW Healthcare, Dept Surg, Evanston, IL USA. RP Sturgeon, C (reprint author), NW Mem Hosp, Dept Surg, 675 N St Clair St,Galter 10-105, Chicago, IL 60611 USA. EM csturgeo@nmh.org NR 42 TC 245 Z9 276 U1 5 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2007 VL 246 IS 3 BP 375 EP 384 DI 10.1097/SLA.0b013e31814697d9 PG 10 WC Surgery SC Surgery GA 206HQ UT WOS:000249174900004 PM 17717441 ER PT J AU Black, D Specht, M Lee, JM Dominguez, F Gadd, M Hughes, K Rafferty, E Smith, B AF Black, Dalliah Specht, Michelle Lee, Janie M. Dominguez, Francisco Gadd, Michele Hughes, Kevin Rafferty, Elizabeth Smith, Barbara TI Detecting occult malignancy in prophylactic mastectomy: Preoperative MRI versus sentinel lymph node biopsy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE prophylactic mastectomy; breast MRI; sentinel lymph node biopsy; occult cancer; cost analysis ID DIAGNOSED BREAST-CANCER; CONTRALATERAL BREAST; HEREDITARY RISK; FAMILY-HISTORY; WOMEN; EFFICACY; MAMMOGRAPHY; CARRIERS; LESIONS; BRCA1 AB Background: High-risk patients undergoing prophylactic mastectomy (PM) may have unsuspected cancers identified on pathology. The optimum way to identify and manage them is controversial. Magnetic resonance imaging (MRI) may identify occult cancer preoperatively. Sentinel lymph node biopsy (SLNB) allows intraoperative staging and axillary dissection during the same operation. We determined the efficacy and cost of MRI and/or SLNB in managing high-risk PM patients. Methods: We reviewed 192 PMs in 173 patients from 1999 to 2005. Costs were estimated for MRI and SLNB during PM by the 2005 Medicare Resource-Based Relative Value Scale. We also estimated costs and procedures for the four strategies in a larger hypothetical cohort. Results: A total of 19 (10%) of 192 PMs contained occult cancers, 14 ductal carcinoma-in-situ (DCIS) and 5 invasive ductal carcinoma (IDC). In 59 patients, MRI detected an IDC but missed two DCIS and an IDC. Positive MRIs generated an additional average cost of $1207 per patient. In 56 PMs with SLNB, 6 occult cancers were found, 5 DCIS and 1 IDC, all with negative SLNBs. Adding a SLNB costs an additional average of $644. A theoretical analysis demonstrated that PM alone costs $808 per patient, PM with SLNB costs $1420, PM with MRI and selective SLNB costs $1774, and PM with routine MRI and SLNB costs $2379. Conclusions: MRI adds great cost and misses most occult cancers in PMs. SLNB allows the rare patient with occult IDC to avoid axillary dissection but adds cost. Given the low rate of unsuspected invasive cancers and the costs of MRI and SLNB, neither is recommended as standard practice for PM patients. C1 Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Breast Imaging, Boston, MA 02114 USA. RP Specht, M (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Yawkey Bldg,7th Floor,55 Fruit St, Boston, MA 02114 USA. EM mspecht@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 19 TC 26 Z9 26 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD SEP PY 2007 VL 14 IS 9 BP 2477 EP 2484 DI 10.1245/s10434-007-9356-1 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 209PN UT WOS:000249400600011 PM 17587091 ER PT J AU Dyke, CM Aldea, G Koster, A Smedira, N Avery, E Aronson, S Spiess, BD Lincoff, AM AF Dyke, Cornelius M. Aldea, Gabriel Koster, Andreas Smedira, Nicholas Avery, Edwin Aronson, Solomon Spiess, Bruce D. Lincoff, A. Michael TI Off-pump coronary artery bypass with bivalirudin for patients with heparin-induced thrombocytopenia or antiplatelet factor four/heparin antibodies SO ANNALS OF THORACIC SURGERY LA English DT Article ID CARDIOPULMONARY BYPASS; CARDIAC-SURGERY; ANTICOAGULATION; EXPERIENCE; PROTAMINE AB Background. This study assessed the use of bivalirudin as an alternative anticoagulant in patients with heparin-induced thrombocytopenia- thrombotic syndrome ( HIT/ TS) or antiplatelet factor four- heparin ( anti- PF4/ H) antibodies undergoing off- pump coronary artery bypass ( OPCAB). Methods. In a prospective, open- label, multicenter study, fifty- one patients with documented anti- PF4/ H antibodies and ( or) HIT/ TS underwent OPCAB with bivalirudin anticoagulation ( 0.75 mg/ kg IV bolus, 1.75 mg/ kg/ hour infusion). Procedural success ( absence of death, Q- wave myocardial infarction, repeat revascularization, and stroke), bleeding, and transfusion at day seven/ discharge, thirty days, and twelve weeks were assessed. Results. Thirty- five patients ( 67%) were included with positive anti- PF4/ H antibodies and no thrombocytopenia or thrombosis, eleven patients ( 22%) had thrombocytopenia, penia, and five patients had clinical HIT/ TS ( 10%). Procedural success at seven days/ discharge was achieved in forty- seven patients ( 92%), while procedural success at thirty days and twelve weeks was 88%. There were no deaths. Chest tube output over the first twenty- four hours was 936 +/- 525 mL and twenty- five patients received a red blood cell transfusion during their hospitalization. Two patients required reexploration for persistent postoperative hemorrhage. Conclusions. Bivalirudin was an effective alternative anticoagulant for patients with HIT/ TS or circulating anti- PF4/ H antibodies undergoing OPCAB, with high rates of procedural success and an acceptable incidence of bleeding or transfusions. CARDIOVASCULAR C1 Gaston Mem Hosp, Dept Cardiovasc & Thorac Surg, Gastonia, NC 28054 USA. Washington State Univ, Dept Cardiac Surg, Seattle, WA USA. Deutsch Herzzentrum Berlin, Dept Anesthesia, Berlin, Germany. Cleveland Clin Fdn, Dept Cardiothorac Surg, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Dept Cardiac Anesthesia, Boston, MA 02114 USA. Duke Univ, Med Ctr, Dept Anesthesia, Durham, NC USA. Virginia Commonwealth Univ, Dept Cardiac Surg, Richmond, VA USA. Virginia Commonwealth Univ, Dept Cardiothorac Anesthesia, Richmond, VA USA. Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. RP Dyke, CM (reprint author), Gaston Mem Hosp, Dept Cardiovasc & Thorac Surg, 2555 Court Dr,Suite 200, Gastonia, NC 28054 USA. EM dykec@gmh.org NR 12 TC 40 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2007 VL 84 IS 3 BP 836 EP 840 DI 10.1016/j.athoracsur.2007.04.007 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 203NX UT WOS:000248982400019 PM 17720385 ER PT J AU Zhukovsky, MA Markovic, I Bailey, AL AF Zhukovsky, Mikhail A. Markovic, Ingrid Bailey, Austin L. TI Influence of calcium on lipid mixing mediated by influenza hemagglutinin SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL MEMBRANE-FUSION; CONFORMATIONAL CHANGE; CRYSTAL-STRUCTURE; CYTOPLASMIC TAIL; TEMPERATURE; EXOCYTOSIS; LIPOSOMES; MECHANISM; PROTEINS AB We studied the influence of calcium on lipid mixing mediated by influenza hemagglutinin (HA). Lipid mixing between HA-expressing cells and liposomes containing disialoganglioside, influenza virus receptor, was studied at 37 C and neutral pH after a low-pH pulse at 4 C. With DSPC/cholesterol liposomes, calcium present after raising the temperature significantly promoted lipid mixing only when it was triggered by a short low-pH application. In case of DOPC/cholesterol liposomes, calcium promotion was observed regardless of the duration of the low-pH pulse. Calcium present during a short, but not long, low-pH application to HA-expressing cells with bound DSPC/cholesterol liposomes at 4 C inhibited subsequent lipid mixing. We hypothesize that calcium influences lipid mixing because it binds to a vestigial esterase domain of hemagglutinin or causes expulsion of the fusion peptide from an electronegative cavity. We suggest that calcium promotes the transition from early and reversible conformation(s) of low pH-activated HA towards an irreversible conformation that underlies both HA-mediated lipid mixing and HA inactivation. (c) 2007 Elsevier Inc. All rights reserved. C1 Sci Commuicat Cephalon Inc, Hoboken, NJ 07030 USA. Max Planck Inst Biophys Chem, Abt Spektroskopie & Photochem Kinetik Struckturdy, D-37077 Gottingen, Germany. NICHHD, Natl Inst Hlth, Lab Cellular & Mol Biol, Sect Membrane Biol, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Zhukovsky, MA (reprint author), Ctr Drug Evaluat & Res, US FDA, Bethesda, MD 20892 USA. EM mzhukov@gwdg.de FU Intramural NIH HHS [Z01 HD001501-16] NR 58 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 2007 VL 465 IS 1 BP 101 EP 108 DI 10.1016/j.abb.2007.05.005 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 206IF UT WOS:000249176400012 PM 17585869 ER PT J AU Akilov, OE Donovan, MJ Stepinac, T Carter, CR Whitcomb, JP Hasan, T McDowell, MA AF Akilov, Oleg E. Donovan, Michael J. Stepinac, Thomas Carter, Cristina R. Whitcomb, James P. Hasan, Tayyaba McDowell, Mary Ann TI T helper type 1 cytokines and keratinocyte growth factor play a critical role in pseudoepitheliomatous hyperplasia initiation during cutaneous leishmaniasis SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE leishmaniasis; hyperplasia; keratinocyte; growth factor; cytokine ID TUMOR-NECROSIS-FACTOR; MESSENGER-RNA EXPRESSION; SMOOTH-MUSCLE-CELLS; FACTOR-KAPPA-B; FACTOR-ALPHA; FACTOR RECEPTORS; GENE-EXPRESSION; HUMAN SKIN; PSORIASIS; LYMPHOMA AB Pseudoepitheliomatous hyperplasia (PEH) is an exuberant proliferation of the epidermis. The underlying mechanism(s) that lead to PEH have not been completely elucidated. Here, we characterize PEH during the healing stages of cutaneous leishmanial ulcers in mice. During experimental cutaneous leishmaniasis (CL) C57BL/6 mice produce PEH, and BALB/c do not. A series of immunohistochemical and immunological studies were performed to identify the secretory products of PEH regulation. We observed that the distribution of TNF-alpha and IFN-gamma under PEH had a stripe-like diffuse pattern and localized in the upper part of the papillary dermis directly under the proliferating epidermis. Macrophages were identified as the major source of TNF-alpha (56.3%). The importance of IFN-gamma and TNF-alpha in PEH development was proven by the initiation of PEH after three intralesional injections of TNF-alpha and IFN-gamma every three days in infected BALB/c mice. In C57BL/6 mice, keratinocyte growth factor (KGF) expressing cells were found immediately under the basal membrane of the hyperplastic epidermis in comparison with sporadic KGF positive cells deep in the dermis of BALB/c mice. Quantitative RT-PCR analysis demonstrated increased KGF and KGF receptor expression in uninfected C57BL/6 mice as compared to BALB/c mice. These data indicate that Th1 cytokines and KGF play a critical role in PEH initiation during CL. C1 Univ Notre Dame, Dept Biol Sci, Ctr Global Hlth & Infect Dis, Notre Dame, IN 46656 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. RP McDowell, MA (reprint author), Univ Notre Dame, Dept Biol Sci, Ctr Global Hlth & Infect Dis, Notre Dame, IN 46656 USA. NR 67 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD SEP PY 2007 VL 299 IS 7 BP 315 EP 325 DI 10.1007/s00403-007-0765-6 PG 11 WC Dermatology SC Dermatology GA 201WN UT WOS:000248863400002 PM 17643254 ER PT J AU Yeh, C Bowers, D Hadlock, TA AF Yeh, Cory Bowers, Daniel Hadlock, Tessa A. TI Effect of FK506 on functional recovery after facial nerve injury in the rat SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID SCIATIC-NERVE; TACROLIMUS FK506; REGENERATION; ALLOGRAFTS; INCREASES; MECHANISM; NEURONS; CRUSH; MODEL AB Objective: To examine the effect of the immunosuppressive agent FK506 on the rate of functional recovery of the rat facial nerve after crush injury. Methods: Forty rats underwent facial nerve crush injury and were randomly assigned to 4 experimental groups: isotonic sodium chloride solution control, FK binding protein 52 (FKBP-52) antibody control, FK506, and FK506 and FKBP-52 antibody. Rats underwent daily recovery testing from postoperative day 9 until postoperative day 21 by videotaping 3 validated variables in this model: blink reflex return, vibrissial fibrillation loss, and return of vibrissial sweeping symmetry. Results: FK506-treated animals demonstrated improved recovery in all 3 variables compared with control animals. The FK506 and FKBP-52 antibody group demonstrated improved recovery of only the return of the blink reflex. Conclusions: FK506 accelerated functional recovery of facial nerve function after crush injury. Neuroregeneration was inhibited by FKBP-52 antibody in the rat midface but not the upper face. FK506 may be a viable adjuvant treatment for facial nerve neurapraxic injury. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Yeh, C (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM cyeh@partners.org NR 25 TC 26 Z9 28 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD SEP-OCT PY 2007 VL 9 IS 5 BP 333 EP 339 DI 10.1001/archfaci.9.5.333 PG 7 WC Surgery SC Surgery GA 211HT UT WOS:000249515600005 PM 17875826 ER PT J AU Yehuda, R Teicher, MH Seckl, JR Grossman, RA Morris, A Bierer, LM AF Yehuda, Rachel Teicher, Martin H. Seckl, Jonathan R. Grossman, Robert A. Morris, Adam Bierer, Linda M. TI Parental posttraumatic stress disorder as a vulnerability factor for low cortisol trait in offspring of holocaust survivors SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PRENATAL EXPOSURE; MATERNAL-CARE; DUTCH FAMINE; PTSD; TRAUMA; SCHIZOPHRENIA; SEVERITY; DISEASE; RISK; RAPE AB Context: Lower cortisol levels in posttraumatic stress disorder ( PTSD) may reflect a preexisting vulnerability associated with developing the disorder after trauma exposure. Because offspring of trauma survivors with PTSD have a greater prevalence of PTSD after their own life events than offspring of trauma survivors without PTSD and offspring of nonexposed persons, examination of patterns of basal cortisol secretion in such offspring provides an opportunity to test this hypothesis. Objective: To characterize the patterns of basal cortisol secretion in offspring of Holocaust survivors with and without parental PTSD and children of nonexposed parents. Design: Cortisol secretion was measured every 30 minutes for 24 hours. The raw hormonal data were subjected to a chronobiological analysis by applying single-oscillator and multioscillator cosinor analyses, a nonlinear least squares curve-fitting program, to determine circadian and ultradian regulatory dynamics. Setting: The study was conducted under controlled conditions at the General Clinical Research Center at the Mount Sinai School of Medicine. Participants: Twenty-three Holocaust offspring with parental PTSD and 10 without parental PTSD were compared with 16 children of nonexposed parents. No participant had PTSD. Main Outcome Measures: Mean cortisol levels during the 24-hour cycle and other chronobiological parameters ( amplitude, acrophase, circadian quotient, and goodness-of-fit coefficient) derived from singleoscillator and multioscillator models. Results: Offspring with parental PTSD displayed lower mean cortisol levels, reflected by the circadian mesor and reduced cortisol amplitude, compared with offspring without parental PTSD and children of nonexposed parents. This effect seemed to be specifically related to the presence of maternal PTSD. Conclusions: Low cortisol levels and other chronobiological alterations in offspring are associated with the risk factor of maternal PTSD, raising the possibility that these alterations are acquired via glucocorticoid programming either from in utero exposures or in response to maternal behaviors early in life. C1 James J Peters Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Program, Bronx, NY USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Dev Biopsychiat Res Program, Belmont, MA 02178 USA. Univ Edinburgh, Queens Med Res Inst, Endocrinol Unit, Edinburgh, Midlothian, Scotland. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, Dept Psychiat, 130 W Kingsbridge Rd,116A, Bronx, NY 10468 USA. EM rachel.yehuda@va.gov RI Seckl, Jonathan/C-3555-2013 FU NCRR NIH HHS [M01 RR00071]; NIMH NIH HHS [R01 MH64675-01] NR 39 TC 84 Z9 87 U1 2 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2007 VL 64 IS 9 BP 1040 EP 1048 DI 10.1001/archpsyc.64.9.1040 PG 9 WC Psychiatry SC Psychiatry GA 206AS UT WOS:000249156900007 PM 17768269 ER PT J AU Castelo, JMB Courtney, MG Melrose, RJ Stern, CE AF Castelo, J. Mimi Boer Courtney, Maureen G. Melrose, Rebecca J. Stern, Chantal E. TI Putamen hypertrophy in nondemented patients with human immunodeficiency virus infection and cognitive compromise SO ARCHIVES OF NEUROLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; HIV-ASSOCIATED DEMENTIA; CEREBRAL VOLUME LOSS; BASAL GANGLIA; AIDS; BRAIN; DYSFUNCTION; DEPENDENCE; MORPHOLOGY; DISEASE AB Background: Documented death and dysfunction of basal ganglia cells in patients seropositive for human immunodeficiency virus (HIV) suggest that the virus may cause structural compromise to these regions. Objectives: To examine subcortical volumes in non-demented patients seropositive for HIV (HIV+) by means of a novel automated neuroanatomic morphometric analysis tool, and to investigate relationships among cognitive function, immune health, and subcortical volumes. Design and Setting: Cross-sectional study of subcortical morphometry and cognitive function conducted at the Boston University Center for Memory and Brain and the Massachusetts General Hospital Athinoula A. Martinos Center for Biomedical Imaging. Patients: Twenty-two nondemented HIV+ patients and 22 age- and education-matched healthy control participants. Main Outcome Measures: Subcortical segmentation volumes, neuropsychological performance, and immunological variables. Results: Nondemented HIV+ patients demonstrated relative and isolated putamen hypertrophy compared with control participants. Putamen volume enlargement in HIV+ patients was related to motor slowing and immune status, such that higher CD4 lymphocyte levels were associated with larger putamen volumes. There were no other subcortical volume differences between the groups. Conclusions: This study suggests that basal ganglia hypertrophy accompanies HIV-related mild cognitive compromise. These findings may represent a structural imaging parallel to functional imaging studies demonstrating basal ganglia hypermetabolism in HIV+ patients with mild cognitive compromise and early HIV-associated brain disease. C1 Boston Univ, Ctr Memory & Brain, Neuroimaging Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Biomed Imaging, Charlestown, MA USA. RP Castelo, JMB (reprint author), Boston Univ, Ctr Memory & Brain, Neuroimaging Lab, 2 Cummington St,Room 109, Boston, MA 02215 USA. EM mboer@bu.edu FU NCRR NIH HHS [RR14075]; NIMH NIH HHS [P50 MH071702]; NINDS NIH HHS [F31 NS052126, F31 NS054570, R01 NS040239, R01 NS40239] NR 27 TC 31 Z9 32 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 2007 VL 64 IS 9 BP 1275 EP 1280 DI 10.1001/archneur.64.9.1275 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 208TP UT WOS:000249342400007 PM 17846265 ER PT J AU Wiggs, JL AF Wiggs, Janey L. TI Macular degeneration - Risk factors for progression SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID COMPLEMENT FACTOR-H; POLYMORPHISM; VARIANT; GENE; SUSCEPTIBILITY; INCREASES C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2007 VL 125 IS 9 BP 1264 EP 1265 DI 10.1001/archopht.125.9.1264 PG 2 WC Ophthalmology SC Ophthalmology GA 208TM UT WOS:000249342100016 PM 17846368 ER PT J AU Tang, MH Caruso, PA Cunningham, MJ AF Tang, Michael H. Caruso, Paul A. Cunningham, Michael J. TI Radiology quiz case 2 - Diagnosis: Dual ectopic subhyoid and lingual throids SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID THYROID-GLAND C1 Massachusetts Eye & Ear Infirm, Harvard Med Sch, Boston, MA 02114 USA. RP Tang, MH (reprint author), Massachusetts Eye & Ear Infirm, Harvard Med Sch, Boston, MA 02114 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD SEP PY 2007 VL 133 IS 9 BP 941 EP 944 DI 10.1001/archotol.133.9.941 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 209NX UT WOS:000249396400017 PM 17875865 ER PT J AU Shah, SS Chandan, VS Wilbur, DC Khurana, KK AF Shah, Sejal S. Chandan, Vishal S. Wilbur, David C. Khurana, Kamal K. TI Glial fibrillary acidic protein and CD57 immunolocalization in cell block preparations is a useful adjunct in the diagnosis of pleomorphic adenoma SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol ID FINE-NEEDLE-ASPIRATION; SALIVARY-GLAND NEOPLASMS; CYSTIC CARCINOMA; DIFFERENTIAL-DIAGNOSIS; S-100 PROTEIN; BIOPSY; CYTOLOGY; TUMORS; MANAGEMENT; SMEARS AB Context. - The cytologic distinction between pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) can be diagnostically challenging in aspirate smears. Hence a cytologic diagnosis of "atypical cytology'' with a differential diagnosis including PA and ACC is occasionally rendered in a subset of salivary gland fine-needle aspirations. Objective. - To evaluate the role of glial fibrillary acidic protein (GFAP) and CD57 expression in cell block material obtained during fine-needle aspiration procedure in differentiating PA from ACC. Design. - We performed GFAP and CD57 immunostains on formalin-fixed, paraffin-embedded cell block sections of 26 salivary gland fine-needle aspiration cases with the following cytologic diagnoses: ( 1) PA ( 10 cases); ( 2) atypical cytology, cannot exclude ACC ( 8 cases); and ( 3) ACC ( 8 cases). Results. - All 10 (100%) cases with cytologic diagnoses of PA were positive for GFAP, and 8 (80%) of 10 cases were positive for CD57; tissue follow-up confirmed the diagnosis of PA in all cases. All 8 ( 100%) cases with cytologic diagnosis of ACC were negative for both GFAP and CD57; tissue follow-up confirmed the diagnoses of ACC in all cases. Of the 8 cases with diagnoses of atypical cytology, 4 (50%) were negative and 4 ( 50%) were positive for both GFAP and CD57. Subsequent tissue follow-up in these cases revealed 4 cases of ACC ( all negative for GFAP and CD57) and 4 cases of PA ( all positive for GFAP and CD57). Conclusions. - Our results show that positive staining for GFAP and CD57 serves as a useful adjunct for the diagnosis of PA and helps to reduce the uncertainty in challenging cases. C1 SUNY Upstat Med Univ, Dept Pathol, Syracuse, NY 13210 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Khurana, KK (reprint author), SUNY Upstat Med Univ, Dept Pathol, 750 E Adams St, Syracuse, NY 13210 USA. EM khuranak@upstate.edu RI Chandan, Vishal/K-8860-2015 NR 22 TC 6 Z9 6 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2007 VL 131 IS 9 BP 1373 EP 1377 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 209NE UT WOS:000249394400010 PM 17824792 ER PT J AU Mack, JW Patrick, J Goldmann, DA Weeks, JC Cleary, PD AF Mack, Jennifer W. Patrick, John Goldmann, Donald A. Weeks, Jane C. Cleary, Paul D. TI Quality of health care for children - Role of health and chronic illness in inpatient care experiences SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PATIENT SATISFACTION; MEDICAL-CARE; NEEDS; PARENTS; VIEWS; PERFORMANCE; CONTINUITY; ACCESS; PLANS AB Objective: To assess how parent reports about the inpatient care of their children vary according to the health status of children with and without chronic conditions. Design: We analyzed parent responses to the Picker Institute Pediatric Inpatient Survey. Setting: Thirty-nine hospitals between January 1, 1997, and December 31, 1999. Participants: Overall, 12 562 parents of children who received inpatient care at participating hospitals. Main Outcome Measure: Parent rating of overall quality of care. Results: Fifty-one percent of parents reported that their child had a chronic condition. Quality-of-care ratings varied according to health status and the presence of chronic conditions. Parents of children in the worst (fair or poor) health without chronic conditions reported lower quality of care (P <. 001) and more care problems (P <. 001) than did those with chronic conditions. Parents of children in the best (excellent, very good, or good) health tended to rate care highly, whether or not their children had chronic conditions. In a multivariable model, the decrement in perceived quality of care associated with poorer health was greater for those without than for those with chronic conditions (P <. 001). Conclusions: Although children in poor health are at risk for experiencing a lower quality of health care, parents of such children who have chronic conditions report fewer care-related problems. This may be owing to the more frequent health care interactions and better continuity of care for children with chronic conditions. C1 Dana Farber Canc Inst, Childrens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Child & Adolescent Hlth Policy, Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Yale Univ, Inst Healthcare Improvement, New Haven, CT USA. Yale Univ, Sch Publ Hlth, New Haven, CT USA. RP Mack, JW (reprint author), Dana Farber Canc Inst, Childrens Hosp, Dept Med, 44 Binney St, Boston, MA 02115 USA. EM Jennifer_mack@dfci.harvard.edu FU AHRQ HHS [T32 HS00063] NR 38 TC 11 Z9 11 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD SEP PY 2007 VL 161 IS 9 BP 828 EP 834 DI 10.1001/archpedi.161.9.828 PG 7 WC Pediatrics SC Pediatrics GA 206AR UT WOS:000249156800003 PM 17768281 ER PT J AU Landry, GJ Liem, TK Mitchell, EL Edwards, JM Moneta, GL AF Landry, Gregory J. Liem, Timothy K. Mitchell, Erica L. Edwards, James M. Moneta, Gregory L. TI Factors affecting symptomatic vs asymptomatic vein graft stenoses in lower extremity bypass grafts SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the Pacific-Coast-Surgical-Association CY FEB 18, 2007 CL Kohala Coast, HI SP Pacific Coast Surg Assoc ID DUPLEX SCAN SURVEILLANCE; PATENCY; REVISION; REPAIR AB Objective: To determine differences in patients undergoing lower extremity vein graft revisions presenting with and without recurrence of preoperative symptoms. Design: Retrospective case-control study of a prospectively maintained database. Setting: University and veterans' administration hospitals Patients: Two hundred nineteen lower extremity vein graft revisions were performed in 161 patients from January 1995 to January 2007. Patients were categorized as asymptomatic or symptomatic (recurrence of initial symptoms) at the time of revision. Main Outcome Measures: Univariate analysis was performed to assess differences in patient demographics, details of initial operation, site of recurrent lesion, and follow-up surveillance data between symptomatic and asymptomatic patients. Independent predictors of symptomatic recurrence were identified with multivariate logistic regression. Primary assisted patency was compared between revisions performed for symptomatic and asymptomatic lesions. Results: Vein graft stenoses were asymptomatic in 125 cases (57%) and symptomatic in 94 cases (43%). Symptomatic recurrences were associated with a significantly greater drop in ankle brachial index than asymptomatic lesions (mean [SD], 0.21 [0.03] vs 0.11 [0.021; P=.003). Distal graft or outflow lesions were significantly associated with symptom recurrence (P=.048). Multivariate analysis identified ankle brachial index decrease (odds ratio, 6.803; 95% confidence interval, 1.418-32.258; P=.02) and the use of alternate graft conduit (odds ratio, 2.633,95% confidence interval, 1.243-5.578; P=.01) as independent predictors of recurrent symptoms. Overall 5-year patency was the same regardless of preoperative symptoms (82% symptomatic and 88% asymptomatic; P=30). Conclusions: Symptomatic recurrences are associated with larger decreases in ankle brachial index, distal lesions, and alternate conduit grafts. Duplex surveillance is necessary to identify asymptomatic vein graft stenoses. Because graft patency is independent of preoperative symptoms, surveillance consisting of clinical follow-up with ankle brachial index evaluation warrants further consideration. C1 Oregon Hlth & Sci Univ, Dept Surg, Div Vasc Surg, Portland, OR 97239 USA. Portland VA Med Ctr, Dept Surg, Portland, OR USA. RP Landry, GJ (reprint author), Oregon Hlth & Sci Univ, Dept Surg, Div Vasc Surg, 3181 SW Sam Jackson Pk Rd,Mail Code OP11, Portland, OR 97239 USA. EM landryg@ohsu.edu NR 18 TC 5 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD SEP PY 2007 VL 142 IS 9 BP 848 EP 853 DI 10.1001/archsurg.142.9.848 PG 6 WC Surgery SC Surgery GA 210KB UT WOS:000249454000009 PM 17875839 ER PT J AU Coggins, MP Bloch, KD AF Coggins, Matthew P. Bloch, Kenneth D. TI Nitric oxide in the pulmonary vasculature SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE nitric oxide; pulmonary vasculature; pulmonary hypertension treatment ID SOLUBLE GUANYLATE-CYCLASE; RESPIRATORY-DISTRESS-SYNDROME; DEPENDENT PROTEIN-KINASE; ALVEOLAR-CAPILLARY DYSPLASIA; III GENE-EXPRESSION; ENOS-DEFICIENT MICE; SICKLE-CELL-DISEASE; ACUTE LUNG INJURY; RED-BLOOD-CELLS; SYNTHASE TYPE-I AB Homeostasis in the pulmonary vasculature is maintained by the actions of vasoactive compounds, including nitric oxide (NO). NO is critical for normal development of the pulmonary vasculature and continues to mediate normal vasoregulation in adulthood. Loss of NO bioavailability is one component of the endothelial dysfunction and vascular pathology found in pulmonary hypertension (PH). A broad research effort continues to expand our understanding of the control of NO production and NO signaling and has generated novel theories on the importance of pulmonary NO production in the control of the systemic vasculature. This understanding has led to exciting developments in our ability to treat PH, including inhaled NO and phosphodiesterase inhibitors, and to several promising directions for future therapies using nitric oxide-donor compounds, stimulators of soluble guanylate cyclase, progenitor cells expressing NO synthase (NOS), and NOS gene manipulation. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Coggins, MP (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM mcoggins@partners.org NR 113 TC 70 Z9 76 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 2007 VL 27 IS 9 BP 1877 EP 1885 DI 10.1161/ATVBAHA.107.142943 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 205AI UT WOS:000249084700004 PM 17541026 ER PT J AU Monach, PA Verschoor, A Jacobs, JP Carroll, MC Wagers, AJ Benoist, C Mathis, D AF Monach, Paul A. Verschoor, Admar Jacobs, Jonathan P. Carroll, Michael C. Wagers, Amy J. Benoist, Christophe Mathis, Diane TI Circulating C3 is necessary and sufficient for induction of auto antibody-mediated arthritis in a mouse model SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; ALTERNATIVE COMPLEMENT PATHWAY; GENE-EXPRESSION PROFILES; RHEUMATOID-ARTHRITIS; SYNOVIAL-FLUID; GLUCOSE-6-PHOSPHATE ISOMERASE; POLYMORPHONUCLEAR LEUKOCYTES; AUTOIMMUNE ARTHRITIS; REGULATORY PROTEINS; MICROARRAY ANALYSIS AB Objective. For the inflammation characteristic of rheumatoid arthritis, the relative contribution of mediators produced locally in the synovium versus those circulating systemically is unknown. Complement factor C3 is made in rheumatoid synovium and has been proposed to be a crucial driver of inflammation. The aim of this study was to test, in a mouse model of rheumatoid arthritis, whether C3 synthesized within the synovium is important in promoting inflammation. Methods. Radiation bone marrow chimeras between normal and C3(-/-) mice were constructed in order to generate animals that expressed or lacked expression of C3 only in hematopoietic cells. Parabiotic mice were made by surgically linking C3(-/-) mice to irradiated wild-type mice to obtain animals having C3 only in the circulation. Arthritis was induced by injection of serum from arthritic K/BxN mice. Results. In bone marrow chimeras, synthesis of C3 by radioresistant cells was necessary and sufficient to confer susceptibility to serum-transferred arthritis. Parabionts having C3 only in the circulation remained sensitive to arthritis induction, and the cartilage of these arthritic mice contained deposits of C3. Conclusion. In a mouse model in which the alternative pathway of complement activation is critical to the induction of arthritis by autoantibodies, circulating C3 was necessary and sufficient for arthritis induction. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl,Room 475, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu OI Jacobs, Jonathan/0000-0003-4698-0254 FU NIAID NIH HHS [P01-AI-52343]; NIAMS NIH HHS [R01 AR046580, R01 AR046580-09, R01-AR-46580] NR 51 TC 14 Z9 14 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2007 VL 56 IS 9 BP 2968 EP 2974 DI 10.1002/art.22859 PG 7 WC Rheumatology SC Rheumatology GA 215TT UT WOS:000249832600018 PM 17763447 ER PT J AU O'Cleirigh, C Ironson, G Smits, JAJ AF O'Cleirigh, Conall Ironson, Gail Smits, Jasper A. J. TI Does distress tolerance moderate the impact of major life events on psychosocial variables and behaviors important in the management of HIV? SO BEHAVIOR THERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; SUBSTANCE USE DISORDERS; PSYCHOLOGICAL DISTRESS; VIRAL LOAD; MEDICATION ADHERENCE; DEPRESSIVE SYMPTOMS; DISEASE PROGRESSION; GAY MEN; ANXIETY SENSITIVITY AB Living with HIV involves management of multiple stressful disease-related and other life events. Distress tolerance may provide a functional, individual-based context for qualifying the established relationships between major life events and psychosocial variables important in the management of HIV. The present study provided a preliminary test of the hypothesis that distress tolerance moderates the impact of major life events on these predictors of disease progression. HIV-positive patients (n=116) completed psychosocial and medical questionnaires. Results indicated that major life events interacted with distress tolerance such that lower distress tolerance and higher life events were associated with significantly higher levels of depressive symptoms, substance use coping, alcohol and cocaine use, and medication adherence. In addition, distress tolerance was directly related to self-reported HIV-related symptoms. These results suggest that low distress tolerance, particularly in the face of major life events, may present significant challenges to adaptive management of HIV. Distress tolerance assessment may help to specify targets for cognitive-behavioral and stress management treatments for people living with HIV. C1 [O'Cleirigh, Conall; Ironson, Gail] Univ Miami, Coral Gables, FL 33124 USA. [Smits, Jasper A. J.] So Methodist Univ, Dallas, TX 75275 USA. RP O'Cleirigh, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 805 Wang,15 Parkman St, Boston, MA 02115 USA. EM cocleirigh@partners.org RI Smits, Jasper/A-4350-2008; OI Smits, Jasper/0000-0001-7128-9807; Smits, Jasper/0000-0003-1633-9693 FU NIMH NIH HHS [T32MH18917, R01 MH066697, R01 MH066697-04, R01MH066697, R01MH53791, T32 MH018917] NR 58 TC 43 Z9 43 U1 3 U2 5 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD SEP PY 2007 VL 38 IS 3 BP 314 EP 323 DI 10.1016/j.beth.2006.11.001 PG 10 WC Psychology, Clinical SC Psychology GA 323BI UT WOS:000257418600010 PM 17697855 ER PT J AU Frey, BN Andreazza, AC Nery, FG Martins, MR Quevedo, J Soares, JC Kapczinski, F AF Frey, Benicio N. Andreazza, Ana C. Nery, Fabiano G. Martins, Marcio R. Quevedo, Joao Soares, Jair C. Kapczinski, Flavio TI The role of hippocampus in the pathophysiology of bipolar disorder SO BEHAVIOURAL PHARMACOLOGY LA English DT Review DE animal model; bipolar disorder; brain imaging; hippocampus; mood stabilizers; pathophysiology; postmortem ID DORSOLATERAL PREFRONTAL CORTEX; STANLEY NEUROPATHOLOGY CONSORTIUM; DECLARATIVE MEMORY IMPAIRMENT; TEMPORAL-LOBE STRUCTURES; LONG-TERM POTENTIATION; MOOD DISORDERS; MAJOR DEPRESSION; POSTMORTEM BRAIN; RAT HIPPOCAMPUS; NEUROTROPHIC FACTOR AB Bipolar disorder (BD) is thought to be associated with abnormalities within discrete brain regions associated with emotional regulation, particularly in fronto-limbic-subcortical circuits. Several reviews have addressed the involvement of the prefrontal cortex in the pathophysiology of BD, whereas little attention has been given to the role of the hippocampus. This study critically reviews data from brain imaging, postmortem, neuropsychological, and preclinical studies, which suggested hippocampal abnormalities in BD. Most of the structural brain imaging studies did not find changes in hippocampal volume in BD, although a few studies suggested that anatomical changes might be restricted to the psychotic, pediatric, or unmedicated BD subgroups. Functional imaging studies showed abnormal brain activation in the hippocampus and its closely related regions during emotional, attentional, and memory tasks. This is consistent with neuropsychological findings that revealed a wide range of cognitive disturbances during acute mood episodes and a significant impairment in declarative memory during remission. Postmortem studies indicate abnormal glutamate and GABA transmission in the hippocampus of BD patients, whereas data from preclinical studies suggest that the regulation of hippocampal plasticity and survival might be associated with the therapeutic effects of mood stabilizers. In conclusion, the available evidence suggests that the hippocampus plays an important role in the pathophysiology of BD. C1 McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. Hosp Clin Porto Alegre, Bipolar Disorders Program, Porto Alegre, RS, Brazil. Hosp Clin Porto Alegre, Lab Mol Psychiat, Porto Alegre, RS, Brazil. Univ Fed Rio Grande do Sul, ICBS, Dept Biochem, BR-90046900 Porto Alegre, RS, Brazil. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Extremo Sul Catarinense, Program Posgrad Ciencias Saude, Neurosci Lab, Santa Catarina, Brazil. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Psychiat Serv, Audie L Murphy Div, San Antonio, TX USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. RP Frey, BN (reprint author), McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, 3801 Univ St, Montreal, PQ H3A 2B4, Canada. EM benicio.frey@gmail.com RI Andreazza, Ana/B-7485-2008; Kapczinski, Flavio/D-3175-2013; Kapczinski, Flavio/J-5803-2014; Quevedo, Joao/E-5491-2013 OI Quevedo, Joao/0000-0003-3114-6611 NR 143 TC 85 Z9 87 U1 4 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2007 VL 18 IS 5-6 BP 419 EP 430 DI 10.1097/FBP.0b013e3282df3cde PG 12 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 203FK UT WOS:000248960300008 PM 17762510 ER PT J AU Vorup-Jensen, T Waldron, TT Astrof, N Shimaoka, M Springer, TA AF Vorup-Jensen, Thomas Waldron, Travis T. Astrof, Nathan Shimaoka, Motomu Springer, Timothy A. TI The connection between metal ion affinity and ligand affinity in integrin I domains SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE integrin; metal ion; LFA-1; ICAM-1; isothermal calorimetry; surface plasmon resonance ID CD11B A-DOMAIN; ISOTHERMAL TITRATION CALORIMETRY; ACTIVATION; BINDING; CONFORMATIONS; RECOGNITION; SUBUNIT; COMPLEX; CONVERSION; PATHWAY AB Integrins are cell-surface heterodimeric proteins that mediate cell-cell, cell-matrix, and cell-pathogen interactions. Half of the known integrin a subunits contain inserted domains (I domains) that coordinate ligand through a metal ion. Although the importance of conformational changes within isolated I domains in regulating ligand binding has been reported, the relationship between metal ion binding affinity and ligand binding affinity has not been elucidated. Metal and ligand binding by several I domain mutants that are stabilized in different conformations are investigated using isothermal titration calorimetry and surface plasmon resonance studies. This work suggests an inverse relationship between metal ion affinity and ligand binding affinity (i.e. constructs with a high affinity for ligand exhibit a low affinity for metal). This trend is discussed in the context of structural studies to provide an understanding of interplay between metal ion binding and ligand affinities and conformational changes. (c) 2007 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Univ Aarhus, Inst Med Microbiol & Immunol, Biophys Immunol Lab, DK-8000 Aarhus C, Denmark. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu OI Vorup-Jensen, Thomas/0000-0002-4140-6563 FU NCI NIH HHS [CA31798, R01 CA031798, R37 CA031798, R37 CA031798-27]; NIAID NIH HHS [R01 AI072765] NR 29 TC 20 Z9 22 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD SEP PY 2007 VL 1774 IS 9 BP 1148 EP 1155 DI 10.1016/j.bbapap.2007.06.014 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 215WP UT WOS:000249840000009 PM 17702677 ER PT J AU Yang, E Foteinou, PT King, KR Yarmush, ML Androulakis, IP AF Yang, E. Foteinou, P. T. King, K. R. Yarmush, M. L. Androulakis, I. P. TI A novel non-overlapping bi-clustering algorithm for network generation using living cell array data SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION DATA; IFN-GAMMA; IL-6; BINDING; ALPHA; CYTOKINES; PATHWAY; GENOME AB Motivation: The living cell array quantifies the contribution of activated transcription factors upon the expression levels of their target genes. The direct manipulation of the regulatory mechanisms offers enormous possibilities for deciphering the machinery that activates and controls gene expression. We propose a novel bi-clustering algorithm for generating non-overlapping clusters of reporter genes and conditions and demonstrate how this information can be interpreted in order to assist in the construction of transcription factor interaction networks. Contact: Yannis@rci.rutgers.edu. C1 Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, Boston, MA 02114 USA. RP Androulakis, IP (reprint author), Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. FU NIAID NIH HHS [R01 AI063795, AI 063795]; NIBIB NIH HHS [EB 002503, P41 EB002503]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-12] NR 34 TC 18 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD SEP 1 PY 2007 VL 23 IS 17 BP 2306 EP 2313 DI 10.1093/bioinformatics/btm335 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 215OI UT WOS:000249818500014 PM 17827207 ER PT J AU Milad, MR Wright, CI Orr, SP Pitman, RK Quirk, GJ Rauch, SL AF Milad, Mohammed R. Wright, Christopher I. Orr, Scott P. Pitman, Roger K. Quirk, Gregory J. Rauch, Scott L. TI Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anxiety disorders; fear conditioning; fMRI; learning and memory; PTSD; skin conductance response ID POSTTRAUMATIC-STRESS-DISORDER; CONDITIONING PARADIGM; INACTIVATION DISRUPTS; BRAIN ACTIVITY; AMYGDALA; MEMORY; CONTEXT; NEURONS; ANXIETY; STIMULATION AB Background: Extinction of conditioned fear is thought to forma new safety memory that is expressed in the context in which the extinction learning took place. Rodent studies implicate the ventromedial prefrontal cortex (vmPFC) and hippocampus in extinction recall and its modulation by context, respectively. The aim of the present study is to investigate the mediating anatomy of extinction recall in healthy humans. Methods: We used event-related functional magnetic resonance imaging (fMRI) and a 2-day fear conditioning and extinction protocol with skin conductance response as the index of conditioned responses. Results: During extinction recall, we found significant activations in vmPFC and hippocampus in response to the extinguished versus an unextinguished stimulus. Activation in these brain regions was positively correlated with the magnitude of extinction memory. Functional connectivity analysis revealed significant positive correlation between vmPFC and hippocampal activation during extinction recall. Conclusions: These results support the involvement of the human hippocampus as well as vmPFC in the recall of extinction memory. Furthermore, this provides a paradigm for future investigations of fronto-temporal function during extinction recall in psychiatric disorders such as posttraurnatic stress disorder. C1 Massachusetts Gen Hosp, Psyhciat Neurosci Div, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Brigham & Womens Hosp, Div Neurol, Div Congnit & Behav Neurol, Boston, MA 02115 USA. Dept Vet Affairs Med Ctr, Manchester, NH USA. Ponce Sch Med, Dept Physiol, Ponce, PR USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp, Psyhciat Neurosci Div, Dept Psychiat, Bldg 149,13th St,2nd Floor, Charlestown, MA 02129 USA. EM rauch@psych.mgh.harvard.edu FU NIMH NIH HHS [1R21MH072156-1] NR 49 TC 445 Z9 452 U1 11 U2 68 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 1 PY 2007 VL 62 IS 5 BP 446 EP 454 DI 10.1016/j.biopsych.2006.10.011 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 204KP UT WOS:000249042800011 PM 17217927 ER PT J AU Gilbertson, MW Williston, SK Paulus, LA Lasko, NB Gurvits, TV Shenton, ME Pitman, RK Orr, SP AF Gilbertson, Mark W. Williston, Stephanie K. Paulus, Lynn A. Lasko, Natasha B. Gurvits, Tamara V. Shenton, Martha E. Pitman, Roger K. Orr, Scott P. TI Configural cue performance in identical twins discordant for posttraumatic stress disorder: Theoretical implications for the role of hippocampal function SO BIOLOGICAL PSYCHIATRY LA English DT Article DE configural; contextual; hippocampus; neuropsychology; PTSD; twins ID SHORT-TERM-MEMORY; MAGNETIC-RESONANCE; COMBAT VETERANS; AFFECTIVE NEUROSCIENCE; DORSAL HIPPOCAMPUS; VIETNAM VETERANS; SEXUAL ABUSE; VOLUME; CONTEXT; RATS AB Background: A significant subgroup of individuals with posttraumatic stress disorder (PTSD) exhibits chronic, unremitting symptomatology that has also been associated with smaller hippocampal volume. The hippocampus plays a significant role in configural processing of contextual cues that facilitates context-appropriate extinction of conditioned fear. We test the hypothesis that hippocampus-based configural processing deficits are a pre-existing vulnerability factor for unremitting forms of PTSD. Methods: Participants included male monozygotic twin pairs who were discordant for combat trauma. In 18 twin pairs the combatexposed brother developed unremitting PTSD, whereas in 23 pairs the combat-exposed brother never developed PTSD. Participants were compared in the capacity to solve allocentric spatial processing tasks, and this performance was examined for its relationship to the severity of PTSD symptornatology and hippocampal volume. Results: Although not completely differentiated from overall IQ, PTSD combat veterans demonstrated significantly impaired performance in configural processing relative to non-PTSD combat veterans. Despite having neither combat-exposure nor PTSD, the unexposed co-twins of combat veterans with PTSD displayed the same decrements as their brothers. Deficits were significantly related to PTSD severity and hippocampal volume. Conclusions: The current study provides the first evidence that the relevance of the hippocampus in PTSD might be related to pre-existing configural cue processing deficits that predispose individuals to develop unremitting forms of the disorder. C1 Manchester VA Med Ctr, Res Serv 151, Manchester, NH 03104 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. VA Boston Healthcare Syst, Brockton, MA USA. RP Gilbertson, MW (reprint author), Manchester VA Med Ctr, Res Serv 151, 718 Smyth Rd, Manchester, NH 03104 USA. EM mark.gilbertson@med.va.gov FU NIMH NIH HHS [K02 MH001110, K02 MH001110-10, K02-MH01110, R01 MH054636, R01-MH54636] NR 77 TC 56 Z9 57 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2007 VL 62 IS 5 BP 513 EP 520 DI 10.1016/j.biopsych.2006.12.023 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 204KP UT WOS:000249042800019 PM 17509537 ER PT J AU Perlis, RH Purcell, S Fagerness, J Cusin, C Yamaki, L Fava, M Smoller, JW AF Perlis, Roy H. Purcell, Shaun Fagerness, Jesen Cusin, Cristina Yamaki, Lesley Fava, Maurizio Smoller, Jordan W. TI Clinical and genetic dissection of anger expression and CREB1 polymorphisms in major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE aggression; anger; creb; genetic association; major depressive disorder; phenotype ID ELEMENT-BINDING PROTEIN; CORONARY-HEART-DISEASE; NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX; LIFE EVENTS; SUICIDE; ASSOCIATION; HOSTILITY; RISK; IRRITABILITY AB Background: Anger and irritability are prominent in a subset of individuals with major depressive disorder (MDD). Phosphorylation of the transcription factor cyclic adenosine monophosphate (cAMP) Response Element Binding Protein (CREB) has been associated with aggression or reward/aversion in rodents, and markers near CREBI have been linked to MDD. Therefore, we examined the association between CREBI polymorphisms and anger expression in VIDD. Methods: A clinical sample of 94 Caucasian outpatients with MDD (42 male, 52 female) completed the Spielberger State-Trait Anger Expression Inventory. We examined six tagging single nucleoticle polymorphisms (SNPs) spanning CREBI and flanking regions for association with a summary measure of frequency and intensity of anger expression. We also introduced a novel statistical method to dissect the independent effect of individual SNPs and haplotypes. Results: For the sample as a whole, one of six SNPs tested was significantly associated with anger expression (empirical p =.003). Among the male subsample, this association was particularly marked (empirical p = 8 X 10(-5)). A global haplotype test of the six SNPs was likewise significant (p = 3.7 X 10(-6)). No single SNP or haplotype accounted for all of the association observed. Conclusion: These preliminary results suggest a strong, gender-specific association between variation at the CREBI locus and anger expression in MDID. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Perlis, RH (reprint author), 15 Pkman St,WACC 812, Boston, MA 02114 USA. EM rperlis@partners.org NR 56 TC 32 Z9 32 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 1 PY 2007 VL 62 IS 5 BP 536 EP 540 DI 10.1016/j.biopsych.2006.10.034 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 204KP UT WOS:000249042800022 PM 17300755 ER PT J AU Baron, F Sandmaier, BM Storer, BE Maris, MB Langston, AA Lange, T Petersdorf, E Bethge, W Maziarz, RT McSweeney, PA Pulsipher, MA Wade, FC Chauncey, TR Sbizuru, FA Sorror, ML Woolfrey, AE Maloney, DG Storb, R AF Baron, Frederic Sandmaier, Brenda M. Storer, Barry E. Maris, Michael B. Langston, Amelia A. Lange, Thoralf Petersdorf, Effie Bethge, Wolfgang Maziarz, Richard T. McSweeney, Peter A. Pulsipher, Michael A. Wade, Fames C. Chauncey, Thomas R. Sbizuru, Fudith A. Sorror, Mohamed L. Woolfrey, Ann E. Maloney, David G. Storb, Rainer TI Extended mycophenolate mofetil and shortened cyclosporine failed to reduce graft-versus-host disease after unrelated hematopoietic cell transplantation with nonmyeloablative conditioning SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE unrelated hematopoietic cell transplantation; mycophenolate mofetil; cyclosporine; graft-versus-host disease ID BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; HEMATOLOGIC MALIGNANCIES; MYELOID-LEUKEMIA; T-CELLS; ENGRAFTMENT; CHIMERISM; OUTCOMES; THERAPY; RISK AB We previously reported data from 103 patients with hematologic malignancies (median age 54 years) who received peripheral blood stem cell (PBSC) grafts from HLA-matched unrelated donors after nonmycloablative conditioning and were given postgrafting immunosuppression consisting of mycophenolate mofetil (MMF; administered from day 0 until day + 40 with taper through day + 96) and cyclosporine (CSP; given from day -3 to day + 100, with taper through day 180) (historical patients). The incidences of grade II-IV acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were 52% and 49%, respectively, and the 1-year probabilities of relapse, nonrelapse mortality (NRM), and progression-free survival (PFS) were 26%, 18%, and 56%, respectively. Here, we treated 71 patients with hematologic malignancies (median age 56 years) with unrelated PBSC grafts and investigated whether postgrafting immunosuppression with an extended course of NMF, given at full dosing until day + 150 and then tapered through day + 180, and a shortened course of CSP, through day + 80, would promote tolerance induction and reduce the incidence of GVHD (current patients). We observed 77% grade ll-1V aGVHD and 45% extensive cGVHD (P =.03, and P =.43, respectively, in current compared to historical patients). The 1-year probabilities of relapse, NRM, and PFS were 23%, 29%, and 47%, respectively (P =.89, P =.02, and P =.08 compared to the historical patients). We conclude that postgrafting immunosuppression with extended MMF and shortened CSP failed to decrease the incidence of GVHD among unrelated PBSC recipients given nonmyeloablative conditioning. (c) 2007 American Society for Blood and Marrow Transplantation C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Liege, B-4000 Liege, Belgium. Univ Washington, Sch Med, Seattle, WA 98195 USA. Rocky Mt Blood & Marrow Transplant Program, Denver, CO USA. Emory Univ, Atlanta, GA 30322 USA. Univ Leipzig, D-7010 Leipzig, Germany. Univ Tubingen, D-72074 Tubingen, Germany. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Utah, Salt Lake City, UT 84112 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Stanford Univ, Stanford, CA 94305 USA. RP Storb, R (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,PO Box 19024, Seattle, WA 98109 USA. EM rstorb@fhcrc.org FU NCI NIH HHS [K23 CA092058-05, K23 CA092058-03, CA18029, CA49605, P30 CA015704-31, P01 CA049605-15, P30 CA015704-32, P01 CA018029-30, K23 CA092058, P01 CA018029-26, P01 CA049605-17, P01 CA049605-13, P30 CA015704-28, P30 CA015704-30, P01 CA049605, K23 CA092058-02, P01 CA049605-14, P01 CA018029-24, P01 CA078902-09, K23 CA092058-01, P01 CA018029-28, P01 CA018029-31, P01 CA049605-19, P30 CA015704-27, P30 CA015704-26, P30 CA015704-33, P01 CA018029-32, P01 CA018029, P01 CA049605-18, P30 CA015704-34, P30 CA015704-29, CA15704, K23 CA092058-04, CA78902, P30 CA015704, P01 CA078902, CA92058, P01 CA049605-16, P01 CA018029-25, P01 CA018029-29, P01 CA018029-27]; NHLBI NIH HHS [HL088021, K99 HL088021-01, HL36444, P01 HL036444, K99 HL088021, P01 HL036444-27, R00 HL088021] NR 38 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2007 VL 13 IS 9 BP 1041 EP 1048 DI 10.1016/j.bbmt.2007.05.011 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 205YX UT WOS:000249152200006 PM 17697966 ER PT J AU Brown, JR Feng, Y Gribben, JG Neuberg, D Fisher, DC Mauch, P Nadler, LM Freedman, AS AF Brown, Jennifer R. Feng, Yang Gribben, John G. Neuberg, Donna Fisher, David C. Mauch, Peter Nadler, Lee M. Freedman, Arnold S. TI Long-term survival after autologous bone marrow transplantation for follicular lymphoma in first remission SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE autologous; bone marrow transplantation; follicular lymphoma; first remission purging; PCR ID STEM-CELL TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; HIGH-DOSE THERAPY; SECONDARY MYELODYSPLASTIC SYNDROME; ACUTE MYELOGENOUS LEUKEMIA; SALVAGE THERAPY; RISK; CYCLOPHOSPHAMIDE; CHEMOTHERAPY; RITUXIMAB AB The role of autologous stem cell transplantation (ASCT) in the treatment of follicular lymphoma is still being defined in the era of antibody therapy. Here we report the long-term 12-year clinical outcomes of patients treated with autologous bone marrow transplantation (ABMT) for follicular non-Hodgkin's lymphoma (NHL) in first remission. Between 1988 and 1993, advanced-stage follicular NHL patients in need of initial therapy were enrolled in 2 consecutive prospective treatment trials of either standard-dose CHOP induction (83 patients) or high-dose CHOP plus granulocyte-colony stimulating factor (G-CSF) (20 patients). Patients who achieved an adequate remission with induction therapy underwent conditioning with cyclophosphamide and total body irradiation (TBI) followed by ABMT in first remission using bone marrow (BM) purged in vitro with anti-B cell monoclonal antibodies and rabbit complement (96 patients). At 12-year follow-up, 61% of the patients are alive and 43% remain in continuing complete remission. The only predictors of decreased progression-free survival proved to be histologic BM involvement at time of harvest (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.3-3.9, P <.004) and PCR detectable disease in the BM product after purging (HR 4.18, 95% CI 1.99-8.8, P = .0002). No significant predictors of overall survival were identified. These results at 12-year follow-up suggest that a subset of follicular lymphoma patients can experience prolonged survival with ABMT in first remission. (c) 2007 American Society for Blood and Marrow Transplantation C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Med Sch, Dept Med, Boston, MA USA. Harvard Med Sch, Dept Radiat Oncol, Boston, MA USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM arnold_freedman@dfci.harvard.edu FU NCI NIH HHS [2P01CA092625, CA34183, K23 CA115682, K23 CA115682-03, P01 CA092625, P01 CA092625-05, P01 CA092625-07] NR 36 TC 39 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2007 VL 13 IS 9 BP 1057 EP 1065 DI 10.1016/j.bbmt.2007.05.012 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 205YX UT WOS:000249152200008 PM 17697968 ER PT J AU Yeo, Y Bellas, E Highley, CB Langer, R Kohane, DS AF Yeo, Yoon Bellas, Evangelia Highley, Christopher B. Langer, Robert Kohane, Daniel S. TI Peritoneal adhesion prevention with an in situ cross-linkable hyaluronan gel containing tissue-type plasminogen activator in a rabbit repeated-injury model SO BIOMATERIALS LA English DT Article DE peritoneal adhesion; hyaluronan hydrogel; tissue-type plasminogen activator; drug delivery; repeated injury ID UTERINE HORN MODEL; POSTSURGICAL ADHESIONS; FIBRINOLYTIC-ACTIVITY; NITRIC-OXIDE; HYDROGELS; ACID; RAT; REDUCTION; AGENTS AB Postoperative peritoneal adhesions can have serious, potentially lethal consequences. Pharmacotherapy and barrier devices can reduce adhesion formation to varying degrees, but their efficacy is limited by rapid clearance from the peritoneum and lack of biological activity, respectively. To overcome these limitations, we have delivered tissue-type plasminogen activator (tPA), which is deficient in the first 2-3 postoperative days, using a highly cross-linked in situ forming hyaluronan gel (HAX(hx)). We demonstrated this formulation's anti-adhesion activity in a rigorous animal model that involved recurrent adhesions. While non-treated or saline-treated animals developed widespread adhesions (frequency, both 100%; median adhesion area, 12.7 and 15.4cm(2), respectively), tPA delivered by HAX(hx) (tPA-HAX(hx)) was highly effective in preventing recurrent adhesions (frequency, 44%; median adhesion area, 0.1 cm(2)). HAX(hx) itself, tPA solution, and inactivated tPA in HAX(hx) did not provide comparable anti-adhesion activity. tPA-HAX(hx) is a system that is easy to use and potentially promising for adhesion prevention. (c) 2007 Elsevier Ltd. All rights reserved. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Pediat Intens Care, Lab Biomat & Drug Delivery, Boston, MA 02114 USA. RP Kohane, DS (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dkohane@ipartners.org FU NIGMS NIH HHS [GM073626] NR 50 TC 33 Z9 36 U1 3 U2 24 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2007 VL 28 IS 25 BP 3704 EP 3713 DI 10.1016/j.biomaterials.2007.04.033 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 186IO UT WOS:000247772600012 PM 17512979 ER PT J AU Tang, SQ Spector, M AF Tang, Shunqing Spector, Myron TI Incorporation of hyaluronic acid into collagen scaffolds for the control of chondrocyte-mediated contraction and chondrogenesis SO BIOMEDICAL MATERIALS LA English DT Article; Proceedings Paper CT 4th Korea-China Symposium on Biomaterials and Nano-Biotechnology CY OCT 19-24, 2006 CL Jeju Do, SOUTH KOREA SP Korea Sci Engn Fdn, Nat Natural Sci Fdn China ID CROSS-LINKING; GAG SCAFFOLDS; CHITOSAN; MATRIX AB Hyaluronic acid ( HA), a principal matrix molecule in many tissues, is present in high amounts in articular cartilage. HA contributes in unique ways to the physical behavior of the tissue, and has been shown to have beneficial effects on chondrocyte activity. The goal of this study was to incorporate graduated amounts of HA into type I collagen scaffolds for the control of chondrocyte-mediated contraction and chondrogenesis in vitro. The results demonstrated that the amount of contraction of HA/collagen scaffolds by adult canine articular chondrocytes increased with the HA content of the scaffolds. The greatest amount of chondrogenesis after two weeks was found in the scaffolds which had undergone the most contraction. HA can play a useful role in adjusting the mechanical behavior of tissue engineering scaffolds and chondrogenesis in chondrocyte-seeded scaffolds. C1 Jinan Univ, Dept Biomed Engn, Guangzhou 510632, Peoples R China. VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Tang, SQ (reprint author), Jinan Univ, Dept Biomed Engn, Guangzhou 510632, Peoples R China. EM tshunqt@jnu.edu.cn NR 18 TC 20 Z9 20 U1 1 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 J9 BIOMED MATER JI Biomed. Mater. PD SEP PY 2007 VL 2 IS 3 BP S135 EP S141 DI 10.1088/1748-6041/2/3/S10 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 212LM UT WOS:000249597800011 PM 18458458 ER PT J AU Sun, ZX Rosen, O Sampson, AR AF Sun, Zhuoxin Rosen, Ori Sampson, Allan R. TI Multivariate Bernoulli mixture models with application to postmortem tissue studies in schizophrenia SO BIOMETRICS LA English DT Article DE MCMC mixture models; Multivariate Bernoulli distribution; repeated measures; schizophrenia ID VOLUME AB A novel mixture model is presented for repeated measurements in which correlation among repeated observations on the same subject is induced via correlated unobservable component indicators. The mixture components in our model are linear regressions, and the mixing proportions are logits with random effects. Inference is facilitated by sampling from the posterior distribution of the parameters via Markov chain Monte Carlo methods. The model is applied to a neuronal postmortem brain tissue study to examine the differences in neuron volumes between schizophrenic and control subjects. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Texas, Dept Math Sci, El Paso, TX 79968 USA. Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15260 USA. RP Sun, ZX (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM zhuoxin@jimmy.harvard.edu FU NIMH NIH HHS [P50 MH045156] NR 14 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2007 VL 63 IS 3 BP 901 EP 909 DI 10.1111/j.1541-0420.2007.00762.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 203AJ UT WOS:000248947200032 PM 17825019 ER PT J AU Zhu, BG Cai, GF Hall, EO Freeman, GJ AF Zhu, Baogong Cai, Guifang Hall, Emily O. Freeman, Gordon J. TI In-Fusion (TM) assembly: seamless engineering of multidomain fusion proteins, modular vectors, and mutations SO BIOTECHNIQUES LA English DT Article ID GENE AB In-Fusion (TM) can join any two pieces of DNA that have a 15-bp overlap at their ends. The result is equivalent to a recombination event at the ends of the DNAs. The 15-bp overlap may be engineered by inclusion in primers used to PCR amplify a segment of DNA. Originally described for inserting one piece of DNA into a restriction enzyme-digested plasmid, we have found In-Fusion can join four or more pieces of DNA in a single reaction. We used this insight to construct seamless fusion proteins, modular vectors with readily interchangeable segments, and novel mutagenesis strategies. Replacement In-Fusion can be used to delete any desired DNA segment in a plasmid and replace it with any desired new DNA segment without limitations on position or size. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Gordon_Freeman@dfci.harvard.edu NR 13 TC 13 Z9 14 U1 2 U2 10 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 2007 VL 43 IS 3 BP 356 EP 359 DI 10.2144/000112536 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 211GD UT WOS:000249511400018 ER PT J AU Barry, MJ Kantoff, PW Stahl, JE AF Barry, Michael J. Kantoff, Philip W. Stahl, James E. TI Prostate-specific antigen screening for prostate cancer: A decision-analytical perspective SO BJU INTERNATIONAL LA English DT Editorial Material ID BENEFITS; TRENDS; MEN; STRATEGIES; MORTALITY; RISKS C1 Massachusetts Gen Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Hlth Serv Res Program, Boston, MA USA. Inst Technol Assessment, Boston, MA USA. RP Barry, MJ (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. EM Julia_Hayes@dfci.harvard.edu NR 19 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD SEP PY 2007 VL 100 IS 3 BP 486 EP 488 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 196ZU UT WOS:000248523000003 ER PT J AU Ganapathi, KA Austin, KM Lee, CS Dias, A Malsch, MM Reed, R Shimamura, A AF Ganapathi, Karthik A. Austin, Karyn M. Lee, Chung-Sheng Dias, Anusha Malsch, Maggie M. Reed, Robin Shimamura, Akiko TI The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA SO BLOOD LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; BLACKFAN ANEMIA; DYSKERATOSIS-CONGENITA; PROTEOMIC ANALYSIS; DNA-DAMAGE; NUCLEOPHOSMIN; MUTATIONS; GENE; TRANSLATION; BIOGENESIS AB Shwachman-Diamond syndrome (SIDS) is an autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic dysfunction, and leukemia predisposition. Mutations in the SBDS gene are identified in most patients with SDS. SBDS encodes a highly conserved protein of unknown function. Data from SBDS orthologs suggest that SBDS may play a role in ribosome biogenesis or RNA processing. Human SBDS is enriched in the nucleolus, the major cellular site of ribosome biogenesis. Here we report that SBDS nucleolar localization is dependent on active rRNA transcription. Cells from patients with SDS or Diamond-Blackfan anemia are hypersensitive to low doses of actinomycin D, an inhibitor of rRNA transcription. The addition of wild-type SBDS complements the actinomycin D hypersensitivity of SDS patient cells. SBDS migrates together with the 60S large ribosomal subunit in sucrose gradients and coprecipitates with 28S ribosomal RNA (rRNA). Loss of SBDS is not associated with a discrete block in rRNA maturation or with decreased levels of the 60S ribosomal subunit. SBDS forms a protein complex with nucleophosmin, a multifunctional protein implicated in ribosome blogenesis and leukemogenesis. Our studies support the addition of SDS to the growing list of human bone marrow failure syndromes involving the ribosome. C1 Childrens Hosp, Dept Pediat Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Shimamura, A (reprint author), Univ Washington, Dept Pediat Hematol Oncol, 815 Mercer St,Room 356, Seattle, WA 98109 USA. EM shima2@u.washington.edu FU NHLBI NIH HHS [R01 HL079582, R01 HL079582-02, K23 HL068632-03, K23 HL068632] NR 56 TC 77 Z9 80 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2007 VL 110 IS 5 BP 1458 EP 1465 DI 10.1182/blood-2007-02-075184 PG 8 WC Hematology SC Hematology GA 205YT UT WOS:000249151800018 PM 17475909 ER PT J AU zur Wiesch, JS Lauer, GM Timm, J Kuntzen, T Neukamm, M Berical, A Jones, AM Nolan, BE Longworth, SA Kasprowicz, V McMahon, C Wurcel, A Lohse, AW Lewis-Ximenez, LL Chung, RT Kim, AY Allen, TM Walker, BD AF zur Wiesch, Julian Schulze Lauer, Georg M. Timm, Joerg Kuntzen, Thomas Neukamm, Martin Berical, Andrew Jones, Andrea M. Nolan, Brian E. Longworth, Steve A. Kasprowicz, Victoria McMahon, Cory Wurcel, Alysse Lohse, Ansgar W. Lewis-Ximenez, Lia L. Chung, Raymond T. Kim, Arthur Y. Allen, Todd M. Walker, Bruce D. TI Immunologic evidence for lack of heterologous protection following resolution of HCV in patients with non-genotype 1 infection SO BLOOD LA English DT Article ID HEPATITIS-C VIRUS; CD4(+) T-CELLS; PRIMERS PCR-SSP; VIRAL CLEARANCE; IMMUNE-RESPONSES; NONSTRUCTURAL PROTEIN-3; CD8-T-CELL MEMORY; CD4-T-CELL HELP; HLA-B; GENOTYPE AB Chronic hepatitis C virus (HCV) infection is typically characterized by a lack of virus-specific CD4(+) T-cell-proliferative responses, but strong responses have been described in a subset of persons with persistent viremia. One possible explanation for these responses is that they were primed by an earlier resolved infection and do not recognize the current circulating virus. We defined all targeted epitopes using overlapping peptides corresponding to a genotype 1 a strain in 44 patients chronically infected with different HCV genotypes (GT). Surprisingly, more HCV-specific CD4(+) T-cell responses were detected in patients with chronic non-GT1 infection compared with patients with chronic GT1 infection (P =.017). Notably, we found serologic evidence of a previous exposure to GT1 in 4 patients with non-GT1 infection, and these persons also demonstrated significantly more responses than non-GT1 patients in whom genotype and HCV serotype were identical (P <.001). Comparison of recognition of GT1-specific peptides to peptides representing autologous virus revealed the absence of cross-recognition of the autologous circulating virus. These data indicate that persisent HCV infection can occur in the presence of an HCV-specific T-cell response primed against a heterologous HCV strain, and suggest that clearance of 1 GT does not necessarily protect against subsequent exposure to a second GT. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Partners AIDS Res Ctr, Infect Dis Div, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. Univ Klinikum Eppendorf, Med Klin 1, Hamburg, Germany. Heinrich Pette Inst Expt Virol & Immunol, Hamburg, Germany. Univ Essen Gesamthsch, Inst Virol, D-4300 Essen, Germany. Inst Oswaldo Cruz, Dept Virol, BR-20001 Rio De Janeiro, Brazil. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Partners AIDS Res Ctr, Infect Dis Div, 149 13th St,Rm 5212D, Charlestown, MA 02129 USA. EM bwalker@partners.org RI Allen, Todd/F-5473-2011 NR 62 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2007 VL 110 IS 5 BP 1559 EP 1569 DI 10.1182/blood-2007-01-069583 PG 11 WC Hematology SC Hematology GA 205YT UT WOS:000249151800031 ER PT J AU Zhou, JB Goidwasser, MA Li, AH Dahlberg, SE Neuberg, D Wang, HJ Dalton, V McBride, KD Sallan, SE Silverman, LB Gribben, JG AF Zhou, Jianbiao Goidwasser, Meredith A. Li, Aihong Dahlberg, Suzanne E. Neuberg, Donna Wang, Hongjun Dalton, Virginia McBride, Kathryn D. Sallan, Stephen E. Silverman, Lewis B. Gribben, John G. CA Dana-Farber Canc Institute TI Quantitative analysis of minimal residual disease predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium Protocol 95-01 SO BLOOD LA English DT Article ID POLYMERASE-CHAIN-REACTION; RECEPTOR GENE REARRANGEMENTS; IMMUNOGLOBULIN HEAVY-CHAIN; BFM STUDY-GROUP; REAL-TIME PCR; CLINICAL-SIGNIFICANCE; FLOW-CYTOMETRY; T-ALL; CHILDHOOD; QUANTIFICATION AB In a prospective trial in 284 children with B-lineage acute lymphoblastic leukemia (ALL), we assessed the clinical utility of real-time quantitative polymerase chain reaction analysis of antigen receptor gene rearrangements for detection of minimal residual disease (MRD) to identify children at high risk of relapse. At the end of induction therapy, the 5-year risk of relapse was 5% in 176 children with no detectable MRD and 44% in 108 children with detectable MRD (P <.001), with a linear association of the level of MRD and subsequent relapse. Recursive partitioning and clinical characteristics identified that the optimal cutoff level of MRD to predict outcome was 10(-3). The 5-year risk of relapse was 12% for children with MRD less than one leukemia cell per 10(3) normal cells (low MRD) but 72% for children with MRD levels greater than this level (high MRD) (P <.001) and children with high MRD had a 10.5-fold greater risk of relapse. Based upon these results we have altered our treatment regimen for children with B-lineage ALL and children with MRD levels greater than or equal to 10(-3) at the end of 4 weeks of multiagent induction chemotherapy now receive intensified treatment to attempt to decrease their risk of subsequent relapse. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Univ London St Bartholomews Hosp Med Coll, CRUK Med Oncol Dept, Charterhouse Sq, London EC1M 6BQ, England. EM john.gribben@cancer.org.uk FU NCI NIH HHS [CA68484, P01 CA068484] NR 42 TC 68 Z9 84 U1 0 U2 0 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 1 PY 2007 VL 110 IS 5 BP 1607 EP 1611 DI 10.1182/blood-2006-09-045369 PG 5 WC Hematology SC Hematology GA 205YT UT WOS:000249151800037 PM 17485550 ER PT J AU Tai, YT Fulciniti, M Hideshima, T Song, WH Leiba, M Li, XF Rumizen, M Burger, P Morrison, A Podar, K Chauhan, D Tassone, P Richardson, P Munshi, NC Ghobrial, IM Anderson, KC AF Tai, Yu-Tzu Fulciniti, Mariateresa Hideshima, Teru Song, Weihua Leiba, Merav Li, Xian-Feng Rumizen, Matthew Burger, Peter Morrison, Aileen Podar, Klaus Chauhan, Dharminder Tassone, Pierfrancesco Richardson, Paul Munshi, Nikhil C. Ghobrial, Irene M. Anderson, Kenneth C. TI Targeting MEK induces myelorna-cell cytotoxicity and inhibits osteoclastogenesis SO BLOOD LA English DT Article ID HUMAN MULTIPLE-MYELOMA; DEXAMETHASONE-INDUCED APOPTOSIS; BONE-MARROW MICROENVIRONMENT; ACTIVATED PROTEIN-KINASE; VEGF SECRETION; GROWTH; RESISTANCE; PATHWAY; ERK; SURVIVAL AB Activation of the extracellular signal-regulated kinase1/2 (ERK1/2) signaling cascade mediates human multiple myeloma (MM) growth and survival triggered by cytokines and adhesion to bone marrow stromal cells (BMSCs). Here, we examined the effect of AZD6244 (ARRY-142886), a novel and specific MEK1/2 inhibitor, on human MM cell growth in the bone marrow (BM) milieu. AZD6244 blocks constitutive and cytokine-stimulated ERK1/2 phosphorylation and inhibits proliferation and survival of human MM cell lines and patient MM cells, regardless of sensitivity to conventional chemotherapy. Importantly, AZD6244 (200 nM) induces apoptosis in patient MM cells, even in the presence of exogenous interleukin-6 or BMSCs associated with triggering of caspase 3 activity. AZD6244 sensitizes MM cells to both conventional (dexamethasone) and novel (perifosine, lenalidomide, and bortezomib) therapies. AZD6244 down-regulates the expression/secretion of osteoclast (OC)-activating factors from MM cells and inhibits in vitro differentiation of MM patient PBMCs to OCs induced by ligand for receptor activator of NF-kappa B (RANKIL) and macrophage-colony stimulating factor (M-CSF). Finally, AZD6244 inhibits tumor growth and prolongs survival in vivo in a human plasmacytoma xenograft model. Taken together, these results show that AZD6244 targets both MM cells and OCs in the BM microenvironment, providing the preclinical framework for clinical trials to improve patient outcome in MM. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Vet Adm Boston Hlth Care Syst, Boston, MA 02115 USA. RP Tai, YT (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, M551,44 Binney St, Boston, MA 02115 USA. EM yu-tzu-tai@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU PHS HHS [R0-1 50947, P0-1 78378] NR 38 TC 83 Z9 88 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2007 VL 110 IS 5 BP 1656 EP 1663 DI 10.1182/blood-2007-03-081240 PG 8 WC Hematology SC Hematology GA 205YT UT WOS:000249151800043 PM 17510321 ER PT J AU Shin, HK Jones, PB Garcia-Alloza, M Borrelli, L Greenberg, SM Bacskai, BJ Frosch, MP Hyman, BT Moskowitz, MA Ayata, C AF Shin, Hwa Kyoung Jones, Phillip B. Garcia-Alloza, Monica Borrelli, Laura Greenberg, Steven M. Bacskai, Brian J. Frosch, Matthew P. Hyman, Bradley T. Moskowitz, Michael A. Ayata, Cenk TI Age-dependent cerebrovascular dysfunction in a transgenic mouse model of cerebral amyloid angiopathy SO BRAIN LA English DT Article DE cerebral blood flow; laser speckle flowmetry; hypercapnia; whisker stimulation; spreading depression ID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; BLOOD-FLOW; A-BETA; FUNCTIONAL HYPEREMIA; SPREADING DEPRESSION; GLUCOSE-UTILIZATION; LASER SPECKLE; NITRIC-OXIDE; IN-VIVO AB The Tg2576 transgenic mouse model of human cerebral amyloid angiopathy is characterized by age-dependent cerebrovascular deposition of amyloid-beta ( Ab) starting from 9 months of age and progressively worsening to involve most pial arterioles by 18 months; soluble A beta levels are elevated long before vascular deposition takes place in this model. It has been suggested that elevated soluble A beta levels alone are sufficient to impair cerebral blood flow (CBF) regulation thereby contributing to the early progression of Alzheimer's disease. Using laser speckle flowmetry through an intact skull, we studied the impact of elevated soluble A beta levels and vascular A beta deposition on a wide range of CBF responses to evaluate vasodilation and vasoconstriction in young or aged Tg2576 mice. Nineteen-month-old Tg2576 with severe vascular A beta deposits showed an attenuated hyperaemic response during hypercapnia and whisker stimulation compared to wild-type littermates. The anticipated increase in CBF due to isoflurane anaesthesia was also suppressed, as were the typical hypoperfusion responses during cortical spreading depression and alpha-chloralose anaesthesia. The responses of 8-month-old Tg2576 with elevated soluble A beta levels, but without vascular Ab deposition, did not differ fromage-matched controls. In conclusion, our data suggest that vascular A beta deposition is associated with impaired vasodilator as well as vasoconstrictor responses to a wide range of stimuli. These responses do not differ from controls when studied non-invasively prior to vascular A beta deposition, thus challenging the view that elevated soluble A beta levels are sufficient to cause cerebrovascular dysfunction. C1 Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Stroke & Neurovasc Regulat lab, Dept Radiol, Charlestown, MA USA. Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurol, Stroke Serv & Neurosci Intens Care, Charlestown, MA USA. RP Ayata, C (reprint author), Stroke & Neurovasc Regulat Lab, 149 13th St Rm 6403, Charlestown, MA 02129 USA. EM cayata@partners.org OI Jones, Phillip/0000-0003-0525-6323; Garcia-Alloza, Monica/0000-0003-1610-4114 FU NIA NIH HHS [AG08487]; NINDS NIH HHS [P50 NS10828, P01 NS35611, R01 NS061505] NR 59 TC 94 Z9 95 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2007 VL 130 BP 2310 EP 2319 DI 10.1093/brain/awm156 PN 9 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 218UA UT WOS:000250039300009 PM 17638859 ER PT J AU Kelly, MAR Sereika, SM Battista, DR Brown, C AF Kelly, Morgen A. R. Sereika, Susan M. Battista, Deena R. Brown, Charlotte TI The relationship between beliefs about depression and coping strategies: Gender differences SO BRITISH JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Association-for-the-Advancement-of Behavior-Therapy CY NOV, 2005 CL Washington, DC SP Assoc Advancement Behav Therapy ID ILLNESS PERCEPTIONS; COGNITIVE REPRESENTATION; PERSONAL MODELS; PRIMARY-CARE; QUESTIONNAIRE; SYMPTOMS; MOOD; RUMINATION; DISORDERS; INVENTORY AB Objective. Leventhal's common-sense model of illness representation provides a conceptual framework for exploring the relationship between beliefs about depressive illness and use of coping strategies. We explored this relationship among depressed patients both across genders and in terms of gender differences. Design. Depressed primary care patients prescribed antidepressants provided self-report measures of beliefs about depression, emotional reaction to depression, beliefs about medications and coping strategies used. Baseline data from a longitudinal study is presented. Method. Primary data analyses were conducted using canonical correlation analysis, a multivariate statistical method akin to principal component and regression analyses. It allows for parsimonious description of the association between two multivariate sets of variables (in this case, beliefs about depression and coping strategies) by identifying pairs of linear combinations that account for the majority of the between association from the two sets of variables. Results. The sample consisted of 189 depressed primary care patients (70.4% female). Results indicated that emotional reaction to depression is a major factor in determining coping strategies. Greater emotional reaction to depression was associated with maladaptive coping for men and women, while women showed additional relationships between greater perceived control over depression and more adaptive coping techniques as well as between perception of consequences of depression and problem solving. Conclusions. The present research provides preliminary evidence that beliefs about depression are related to coping styles. Further, men and women may differ in the way in which their perceptions about depression influence coping styles adopted. C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. SUNY Buffalo, Buffalo, NY 14260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Kelly, MAR (reprint author), Univ Pittsburgh, Med Ctr, 3811 Ohara St, Pittsburgh, PA 15213 USA. EM kellym2@upmc.edu FU NIMH NIH HHS [R01 MH60763] NR 46 TC 12 Z9 12 U1 1 U2 18 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0144-6657 J9 BRIT J CLIN PSYCHOL JI Br. J. Clin. Psychol. PD SEP PY 2007 VL 46 BP 315 EP 332 DI 10.1348/014466506X173070 PN 3 PG 18 WC Psychology, Clinical SC Psychology GA 201AO UT WOS:000248804100005 PM 17535525 ER PT J AU Hideshima, T Catley, L Raje, N Chauhan, D Podar, K Mitsiades, C Tai, YT Vallet, S Kiziltepe, T Ocio, E Ikeda, H Okawa, Y Hideshima, H Munshi, NC Yasui, H Richardson, PG Anderson, KC AF Hideshima, Teru Catley, Laurence Raje, Noopur Chauhan, Dharminder Podar, Klaus Mitsiades, Constantine Tai, Yu-Tzu Vallet, Sonia Kiziltepe, Tanyel Ocio, Enrique Ikeda, Hiroshi Okawa, Yutaka Hideshima, Hiromasa Munshi, Nikhil C. Yasui, Hiroshi Richardson, Paul G. Anderson, Kenneth C. TI Inhibition of Akt induces significant downregulation of survivin and cytotoxicity in human multiple myeloma cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; Perifosine; Akt; beta-catenin; survivin ID RESISTANCE CAM-DR; PROTEIN-KINASE-B; BETA-CATENIN; THERAPEUTIC IMPLICATIONS; MOLECULAR-MECHANISMS; SIGNALING CASCADES; PLASMA-CELLS; CANCER-CELLS; IN-VITRO; KAPPA-B AB Akt mediates growth and drug resistance in multiple myeloma (MM) cells in the bone marrow (BM) microenvironment. We have shown that a novel Akt inhibitor Perifosine induces significant cytotoxicity in MM cells in the BM milieu. This study further delineated molecular mechanisms whereby Perifosine triggered cytotoxicity in MM cells. Neither the intensity of Jun NH2-terminal kinase phosphorylation nor caspase/poly (ADP-ribose) polymerase cleavage correlated with Perifosine-induced cytotoxicity in MM.1S, INA6, OPM1 and OPM2 MM cells. However, survivin, which regulates caspase-3 activity, was markedly downregulated by Perifosine treatment, without changes in other anti-apoptotic proteins. Downregulation of survivin by siRNA significantly inhibited OPM1 MM cell growth, confirming that survivin mediates MM cell survival. Perifosine significantly downregulated both function and protein expression of beta-catenin. Co-culture with BM stromal cells (BMSCs) upregulated both beta-catenin and survivin expression in MM cells, which was blocked by Perifosine. Importantly, Perifosine treatment also downregulated survivin expression in human MM cells grown in vivo in a severe combined immunodeficient mouse xenograft model. Finally, Perifosine inhibited bortezomib-induced upregulation of survivin, associated with enhanced cytotoxicity of combined bortezomib and Perifosine treatment. These preclinical studies provide the framework for clinical trials of bortezomib with Perifosine to improve patient outcome in MM. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 FU NCI NIH HHS [R0-1 CA 50947, IP50 CA10070]; PHS HHS [P0-1 78378] NR 52 TC 84 Z9 88 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2007 VL 138 IS 6 BP 783 EP 791 DI 10.1111/j.1365-2141.2007.06714.x PG 9 WC Hematology SC Hematology GA 203EQ UT WOS:000248958300013 PM 17760810 ER PT J AU Waters, EA Weinstein, ND Colditz, GA Emmons, KM AF Waters, Erika A. Weinstein, Neil D. Colditz, Graham A. Emmons, Karen M. TI Aversion to side effects in preventive medical treatment decisions SO BRITISH JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article ID RISK COMMUNICATION; BREAST-CANCER; GRAPHICAL DISPLAYS; FREQUENCY FORMATS; INFORMATION; PROBABILITY; UNCERTAINTY; INSTRUCTION; NUMERACY; INTERNET AB Objectives. Individuals may be overly sensitive to the side effects of treatments aimed at preventing illness, in part because they have difficulty in evaluating situations with several possible outcomes that differ in probability. This study tested willingness to undergo a hypothetical preventive treatment and accuracy in determining the probability of harm from the treatment as a function of the presence of a side effect, the initial probability of harm, the format in which probabilities were presented (percentages or frequencies), and the presence or absence of a graphic. Design. The study was a factorial experiment involving 5,251 participants. Methods. Participants recruited from a health-oriented internet site read about a hypothetical cancer prevention treatment situation and were asked to indicate their willingness to accept this treatment and whether it would increase or decrease their overall risk of cancer. The net benefit of the treatment was the same in all conditions, whether or not it was associated with a small side effect. Results. The presence of information about a side effect dramatically decreased willingness to undergo preventive treatment and accuracy in evaluating the treatment's effects. Willingness and accuracy were not influenced by the initial probability of harm, whether the risk probability information was presented as frequencies (N in 100) or as percentages, or whether the initial risk was presented with a bar graph or an array of asterisks or stick figures. Conclusions. Individuals are highly averse to preventive treatments with even small side effects and have difficulty combining the likelihood of positive and negative outcomes to determine the treatment's overall benefits. C1 Rutgers State Univ, Dept Psychol, Piscataway, NJ 08855 USA. Rutgers State Univ, Dept Human Ecol, Piscataway, NJ 08855 USA. Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Waters, EA (reprint author), Canc Prevent Fellowship Program, Natl Canc Inst, 6130 Execut Blvd,EPN Ste 321, Rockville, MD 20852 USA. EM erika.a.waters@gmail.com RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Waters, Erika/0000-0001-7402-0133 NR 35 TC 9 Z9 9 U1 3 U2 6 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 1359-107X J9 BRIT J HEALTH PSYCH JI Br. J. Health Psychol. PD SEP PY 2007 VL 12 BP 383 EP 401 DI 10.1348/135910706X115209 PN 3 PG 19 WC Psychology, Clinical SC Psychology GA 196TT UT WOS:000248505800005 PM 17640453 ER PT J AU Yan, M Roehrl, MH Wang, JY AF Yan, Ming Roehrl, Michael H. Wang, Julia Y. TI Discovery of crystalline inclusions in Bacillus licheniformis that resemble parasporal crystals of Bacillus thuringiensis SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE Bacillus licheniformis; Bacillus thuringiensis; crystal inclusion; crystalline protein ID ELECTRON-MICROSCOPE; SPORULATION; TOXICITY; STRAINS; PROTEIN AB Crystalline inclusions were discovered in stationary and sporulating cells of the spore-forming bacterium Bacillus licheniformis ATCC 9945a. As detected by electron microscopy, dying or sporulating bacterial cells contain a single crystal of strikingly large size. The crystals in sporulating cells are located next to nascent spores and can be several times larger than the spores. Morphologically, most crystals are rhomboid with uniformly spaced grids. These newly discovered crystalline inclusions of B. licheniformis closely resemble parasporal crystals of Bacillus thuringiensis that are formed by insecticidal toxin proteins and used widely as biopesticides. The taxonomic identity of this strain was verified by its 16S rRNA gene sequence and its fatty acid profile. The finding of crystal proteins in B. licheniformis may lead to the discovery of new protein toxins and may expand our pool of biopesticides. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Med, Boston, MA 02114 USA. RP Wang, JY (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM julia_wang@rics.bwh.harvard.edu NR 18 TC 2 Z9 2 U1 1 U2 3 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD SEP PY 2007 VL 53 IS 9 BP 1111 EP 1115 DI 10.1139/W07-076 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 229MD UT WOS:000250807200011 PM 18026233 ER PT J AU Rowe, BH Bota, GW Clark, S Camargo, CA AF Rowe, Brian H. Bota, Gary W. Clark, Sunday Camargo, Carlos A. CA Multictr Airway Res Collaborat Inv TI Comparison of Canadian versus American emergency department visits for acute asthma SO CANADIAN RESPIRATORY JOURNAL LA English DT Article DE admission; asthma; emergency department; practice variation; relapse ID ORAL CORTICOSTEROIDS; DISCHARGE; TRIAL AB BACKGROUND: Acute asthma is a common emergency department (ED) presentation in both Canada and the United States. OBJECTIVE: To compare ED asthma management and outcomes between Canada and the United States. MEHODS: A prospective cohort study of 69 American and eight Canadian EDs was conducted. Patients aged two to 54 years who presented with acute asthma underwent a structured ED interview and telephone follow-up two weeks later. RESULTS: A total of 3031 patients were enrolled. Canadian patients were more likely to be white (89% versus 22%; P<0.001), have health insurance (100% versus 69%; P<0.001) and identify a primary care provider (89% versus 64%; P<0.001). than American patients. In addition, Canadian patients were more likely to be using inhaled corticosteroids (63% versus 44%; P<0.001) and had higher initial peak expiratory flow (61% versus 48%; P<0.001). In the ED, Canadians received fewer beta-agonist (one versus two; P<0.001) and more anticholinergic (two versus one; P<0.001) treatments in the first hour; use of systemic corticosteroids was similar (60% versus 68%; P=0.13). Canadians were less likely to be hospitalized (11% versus 21%; P=0.02). Corticosteroids were prescribed similarly at discharge (60% versus 69%; P=0.13); however, Canadians were discharged more commonly on inhaled corticosteroids (63% versus 11%; P<0.001) and relapses were similar. CONCLUSIONS: Canadian patients with acute asthma have fewer barriers to primary care and are more likely to be on preventive medications, both before the ED visit and following discharge. Admissions rates are higher in the United States; however, relapse after discharge is similar between countries. These findings highlight the influences of preventive practices and heath care systems on ED visits for asthma. C1 [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB T6G 2B7, Canada. [Rowe, Brian H.] Univ Alberta, Sch Publ Hlth, Edmonton, AB T6G 2B7, Canada. [Bota, Gary W.] Sudbury Reg Hosp Corp, Dept Emergency Med, Sudbury, ON, Canada. [Clark, Sunday; Camargo, Carlos A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Rowe, BH (reprint author), Univ Alberta, Dept Emergency Med, 1G1-43 Mackenzie Ctr,8440-112 St, Edmonton, AB T6G 2B7, Canada. EM brian.rowe@ualberta.ca NR 19 TC 29 Z9 29 U1 0 U2 1 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 1198-2241 J9 CAN RESPIR J JI Can. Respir. J. PD SEP PY 2007 VL 14 IS 6 BP 331 EP 337 PG 7 WC Respiratory System SC Respiratory System GA 278GK UT WOS:000254272800004 PM 17885692 ER PT J AU Burstein, HJ Keshaviah, A Baron, AD Hart, RD Lambert-Falls, R Marcom, PK Gelman, R Winer, EP AF Burstein, Harold J. Keshaviah, Aparna Baron, Ari D. Hart, Ronald D. Lambert-Falls, Rosemary Marcom, P. Kelly Gelman, Rebecca Winer, Eric P. TI Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: The trastuzumab and vinorelbine or taxane study SO CANCER LA English DT Article DE trastuzumab; vinorelbine; paclitaxel; docetaxel; HER2; breast cancer ID PHASE-II TRIAL; MONOCLONAL-ANTIBODY; DOCETAXEL; THERAPY; HER2; COMBINATIONS; EFFICACY AB BACKGROUND. The optimal trastuzurnab-based chemotherapy regimen for HER2-overexpressing, metastatic breast cancer is not known. The trastuzurnab and vinorelbine or taxane (TRAVIOTA) study was a prospective, multicenter, randomized trial that was designed to compare these regimens. METHODS. Eligible patients had HER2-overexpressing, metastatic breast cancer and had received no prior chemotherapy for advanced disease. Patients were randomized 1:1 to receive either trastuzumab with weekly vinorelbine therapy or weekly taxane therapy (paclitaxel or clocetaxel at the investigator's choice). Originally planned for 250 patients, the study was closed because of poor accrual with 81 evaluable patients, including 41 patients who received vinorelbine and 40 patients who received taxane. RESULTS. Response rates were 51% and 40% for the vinorelbine/trastuzumab arm and the taxane/trastuzumab arm, respectively (Fisher exact test; P = .37). The median time to disease progression was 8.5 months and 6.0 months for the vinorelbine- and taxane-based arms, respectively (log-rank test; P =.09). Treatment with either regimen generally was well tolerated, yielding comparable rates of neurologic and gastrointestinal toxicity. Vinorelbine-based treatment was associated with more anemia and neutropenia and with 2 episodes of cardiotoxicity Taxane-based therapy was associated with more dermatologic toxicity, myalgias, and fluid retention. CONCLUSIONS. Both vinorelbine/trastuzumab and taxane/trastuzurnab treatments were active as first-line therapy for HER2-positive, metastatic breast cancer and had comparable rates of efficacy and tolerability. The toxicities observed were the result of recognized side effects associated with each of the chemotherapy agents and schedules. These data can inform treatment decision making in this clinical setting. Cancer 2007;110:965-72. (c) 2007American Cancer Society. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA. Calif Pacific Med Ctr, San Francisco, CA USA. Oncol Alliance, Milwaukee, WI USA. S Carolina Oncol Associates, Columbia, SC USA. Duke Univ, Med Ctr, Durham, NC USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org NR 21 TC 113 Z9 118 U1 0 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2007 VL 110 IS 5 BP 965 EP 972 DI 10.1002/cncr.22885 PG 8 WC Oncology SC Oncology GA 206NV UT WOS:000249191100005 PM 17614302 ER PT J AU Montgomery, RB Nelson, PS Lin, D Ryan, CW Garzotto, M Beer, TM AF Montgomery, R. Bruce Nelson, Peter S. Lin, Daniel Ryan, Christopher W. Garzotto, Mark Beer, Tomasz M. TI Diethylstilbestrol and docetaxel - A phase II study of tubulin active agents in patients with metastatic, androgen-independent prostate cancer SO CANCER LA English DT Article DE docetaxel; diethylstilbestrol; chemotherapy; hormone-refractory prostate cancer; estrogen ID MITOXANTRONE PLUS PREDNISONE; TRANSDERMAL ESTRADIOL; ESTRAMUSTINE PHOSPHATE; ESTROGEN; CELLS; CARCINOMA; INHIBITION; THERAPY; INVITRO; TRIAL AB BACKGROUND. The addition of diethylstilbestrol to docetaxel modified tubulin composition and improved the response of prostate cancer to chemotherapy in preclinical models. An attempt was made to recapitulate the observations in a clinical trial. METHODS. Twenty-nine patients with progressive, metastatic, chemotherapy-naive androgen-independent prostate cancer were treated with diethylstilbestrol 1 mg daily and 5 mg on the day before docetaxel and docetaxel 36 mg/m(2) intravenously weekly for 3 weeks of a 4-week cycle. Prophylactic anticoagulation was used in all patients. Patients were assessed by prostate-specific antigen (PSA) monthly and computed tomography (CT) and bone scans every 3 cycles. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria and PSA decline by > 50% maintained for 4 weeks were used to assess activity. RESULTS. The median age was 68 years (range, 56-84 years), Southwest Oncology Group performance status 0 (score range, 0-2), alkaline phosphatase 120 U/L (range, 49-523), hemoglobin (Hgb) 12.6 g/dL (range, 9.2-16.3), PSA 66 ng/dL (range, 4-1962). The median number of cycles administered was 6. Soft tissue metastases were present in 51% of patients and bone metastases in 93%. Twentynine patients are evaluable for response. Of these, 20 patients (69%, 95% confidence interval [CI], 49%-85%) had a PSA decline of >50% and the PSA declined by > 90% in 12 patients (41%, 95% Cl, 23.1%-58.9%). Of 15 patients with measurable disease, 6 (40%, 95% CI, 23.5%-61%) had a partial response. Median time to progression was 6 months (range, 3-19 months). Fifteen patients (51%) suffered grade 3/4 toxicity. Two patients died of causes unrelated to therapy and another died from a steroid-induced ulcer. Six patients developed thrombosis and of those tested 75% had Factor V mutations. Pretreatment PSA, performance status, Hgb, and alkaline phosphatase had no impact on the likelihood of response. CONCLUSIONS. The combination of diethylstilbestrol and docetaxel produces a significant level of activity, measured by PSA decline and measurable disease response rate, and except for venous thrombosis the toxicity appears similar to that seen with docetaxel plus prednisone. These results suggest that tubulin modulation with diethylstilbestrol may improve the therapeutic efficacy of docetaxel and the combination is worthy of further study. Cancer 2007;110:996-1002. (c) 2007 American Cancer Socieity. C1 VA Puget Sound HCSm, Dept Med, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA USA. Seattle Canc Care Alliance, Dept Med Oncol, Seattle, WA USA. VAPSHCS, Dept Urol, Seattle, WA USA. Portland VA Med Ctr, Dept Urol, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Montgomery, RB (reprint author), VA Puget Sound HCSm, Dept Med, 1660 S Columbian Way 111ONC, Seattle, WA 98108 USA. EM rbmontgo@u.washington.edu FU NCI NIH HHS [CA97186] NR 36 TC 13 Z9 17 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2007 VL 110 IS 5 BP 996 EP 1002 DI 10.1002/cncr.22917 PG 7 WC Oncology SC Oncology GA 206NV UT WOS:000249191100009 PM 17639587 ER PT J AU Lanza, E Yu, BB Murphy, G Albert, PS Caan, B Marshall, JR Lance, P Paskett, ED Weissfeld, J Slattery, M Burt, R Iber, F Shike, M Kikendall, JW Brewer, BK Schatzkin, A AF Lanza, Elaine Yu, Binbing Murphy, Gwen Albert, Paul S. Caan, Bette Marshall, James R. Lance, Peter Paskett, Electra D. Weissfeld, Joel Slattery, Marty Burt, Randall Iber, Frank Shike, Moshe Kikendall, James W. Brewer, Brenda K. Schatzkin, Arthur CA Polyp Prevention Trial Study Grp TI The polyp prevention trial-continued follow-up study: No effect of a low-fat, high-fiber, high-fruit, and -vegetable diet on adenoma recurrence eight years after randomization SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SURROGATE END-POINTS; COLORECTAL-CANCER; CARCINOMA SEQUENCE; LIFE-STYLE; RISK; TUMORIGENESIS; QUESTIONNAIRE; INTERVENTION; POLYPECTOMY; NUTRITION AB The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial to evaluate the effects of a high-fiber (18 g/1,000 kcal), high-fruit and -vegetable (3.5 servings/1,000 kcal), and low-fat (20% of total energy) diet on the recurrence of adenomatous polyps in the large bowel over a period of 4 years. Although intervention participants reported a significantly reduced intake of dietary fat, and increased fiber, fruit, and vegetable intakes, their risk of recurrent adenomas was not significantly different from that of the controls. Since the PPT intervention lasted only 4 years, it is possible that participants need to be followed for a longer period of time before treatment differences in adenoma recurrence emerge, particularly if diet affects early events in the neoplastic process. The PPT Continued Follow-up Study (PPT-CFS) was a post-intervention observation of PPT participants for an additional 4 years from the completion of the trial. Of the 1,905 PPT participants, 1,192 consented to participate in the PPT-CFS and confirmed colonoscopy reports were obtained on 801 participants. The mean time between the main trial end point colonoscopy and the first colonoscopy in the PPT-CFS was 3.94 years (intervention group) and 3.87 years (control group). The baseline characteristics of 405 intervention participants and 396 control participants in the PPT-CFS were quite similar. Even though the intervention group participants increased their fat intake and decreased their intakes of fiber, fruits, and vegetables during the PPT-CFS, they did not go back to their prerandomization baseline diet (P < 0.001 from paired t tests) and intake for each of the three dietary goals was still significantly different from that in the controls during the PPT-CFS (P < 0.001 from t tests). As the CFS participants are a subset of the people in the PPT study, the nonparticipants might not be missing completely at random. Therefore, a multiple imputation method was used to adjust for potential selection bias. The relative risk (95% confidence intervals) of recurrent adenoma in the intervention group compared with the control group was 0.98 (0.88-1.09). There were no significant intervention-control group differences in the relative risk for recurrence of an advanced adenoma (1.06; 0.81-1.39) or multiple adenomas (0.92; 0.77-1.10). We also used a multiple imputation method to examine the cumulative recurrence of adenomas through the end of the PPT-CFS: the intervention-control relative risk (95% confidence intervals) for any adenoma recurrence was 1.04 (0.98-1.09). This study failed to show any effect of a low-fat, high-fiber, high-fruit and -vegetable eating pattern on adenoma recurrence even with 8 years of follow-up. C1 NCI, Ctr Canc Res, Lab Can Prevent, Bethesda, MD 20892 USA. Informat Management Serv Inc, Rockville, MD USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. Kaiser Fdn Res Inst, Oakland, CA USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Utah, Salt Lake City, UT USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Vet Affairs Med Ctr, Hines, IL 60141 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Westat Corp, Rockville, MD 20850 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Murphy, G (reprint author), NCI, Ctr Canc Res, Lab Can Prevent, 6116 Execut Blvd,Room 7206, Bethesda, MD 20892 USA. EM murphygw@mail.nih.gov RI Murphy, Gwen/G-7443-2015 NR 40 TC 48 Z9 49 U1 5 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1745 EP 1752 DI 10.1158/1055-9965.EPI-07-0127 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600009 PM 17855692 ER PT J AU Campbell, KL McTiernan, A Li, SSY Sorensen, BE Yasui, Y Lampe, JW King, IB Ulrich, CM Rudolph, RE Irwin, ML Surawicz, C Ayub, K Potter, JD Lampe, PD AF Campbell, Kristin L. McTiernan, Anne Li, Shuying S. Sorensen, Bess E. Yasui, Yutaka Lampe, Johanna W. King, Irena B. Ulrich, Cornelia M. Rudolph, Rebecca E. Irwin, Melinda L. Surawicz, Christina Ayub, Kamran Potter, John D. Lampe, Paul D. TI Effect of a 12-month exercise intervention on the apoptotic regulating proteins Bax and Bcl-2 in colon crypts: a randomized controlled trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PHYSICAL-ACTIVITY; COLORECTAL-CANCER; POSTMENOPAUSAL WOMEN; UNITED-STATES; CARCINOGENESIS; ADENOMAS; RISK; RATS; ONCOPROTEIN; PROGRESSION AB Background: Cellular proliferation and apoptosis (cell death) are highly regulated in the colon as insufficient apoptosis may lead to polyps and cancer. Physical activity decreases risk of colon cancer in observational studies, but the biological basis is not well defined. The objective of this study is to examine the effects of a 12-month aerobic exercise program on expression of proteins that promote (Bax) or inhibit (Bcl-2) apoptosis in colon crypts. Methods: Two hundred two sedentary participants, 40 to 75 years, were randomly assigned to moderate-to-vigorous intensity exercise for 60 min per day, 6 days per week for 12 months, or usual lifestyle. Colon crypt samples were obtained at baseline and 12 months. Bcl-2 and Bax expression was measured by immunohistochemistry. Results: Bax density at the bottom of crypts increased in male exercisers versus controls (+0.87 versus -0.18; P = 0.05), whereas the ratio of Bcl-2 to Bax at the bottom and middle of crypts decreased as aerobic fitness (VO(2)max) increased (P trend = 0.02 and 0.05, respectively). In female exercisers, Bax density in the middle of crypts decreased (-0.36 versus +0.69; P = 0.03) and Bcl-2 to Bax ratio at the top of crypts increased versus controls (+0.46 versus -0.85; P = 0.03). Bax density in the middle of crypts also decreased as minutes per week of exercise increased (P trend = 0.03). Conclusions: A 12-month exercise intervention resulted in greater expression of proteins that promote apoptosis at the bottom of colon crypts in men and decreased expression of proteins that promote apoptosis at the middle and top of colon crypts in women. The difference in effect by gender and location of observed changes warrants further study. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98109 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Dev Program, Seattle, WA 98108 USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Univ Alberta, Dept Publ Hlth Sci, Edmonton, AB, Canada. Yale Univ, Sch Med, Dept Publ Hlth, New Haven, CT 06510 USA. RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, 100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM amctiern@fhcrc.org RI Yasui, Yutaka/E-2564-2015; OI Yasui, Yutaka/0000-0002-7717-8638; Potter, John/0000-0001-5439-1500 FU NCI NIH HHS [R01 CA 77572-01] NR 37 TC 21 Z9 23 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1767 EP 1774 DI 10.1158/1055-9965.EPI-07-0291 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600012 PM 17855695 ER PT J AU Nguyen, PL Zietman, AL AF Nguyen, Paul L. Zietman, Anthony L. TI High-dose external beam radiation for localized prostate cancer: Current status and future challenges SO CANCER JOURNAL LA English DT Article DE prostate cancer; close fractionation; protons; conformal radiotherapy ID RANDOMIZED CONTROLLED-TRIAL; LOCALLY ADVANCED-CARCINOMA; PHASE-III TRIAL; ALPHA/BETA-RATIO; ANDROGEN DEPRIVATION; CONFORMAL RADIOTHERAPY; NORMAL TISSUE; THERAPY; IMRT; CT AB Since the 1960s, external beam radiation has been one of the major curative treatment options for patients with clinically localized prostate cancer. Efforts to improve the efficacy of this modality have focused on delivering a higher dose, and several recent randomized trials have confirmed that this higher dose results in improved oncological outcomes, particularly for patients with intermediate-risk disease. Technological advancements over the past 2 decades have allowed highly conformal treatments that spare more normal tissue and reduce early and long-term treatment side effects. In a complementary fashion, methods have been developed for better real-time localization of the prostate such that radiation fields can be shifted before each treatment to match the daily shifts in the position of the target, leading to greater accuracy and allowing for smaller treatment margins that in turn will overlap with less normal tissue. With newer and more expensive technologies such as intensity-modulated radiation therapy and protons being used with increasing frequency for the treatment of prostate cancer, it becomes imperative to study the risks and benefits of each new modality so that informed cost-benefit decisions can be made. Similarly, there has been a growing interest in hypofractionation as a means of exploiting the supposed low alpha/beta ratio of prostate cancer to shorten overall treatment time and thereby improve convenience and lower costs. However, as with any new technology, it is necessary to proceed with caution in the arena of hypofractionation while we await the results of trials that will help us to determine the long-term risks and benefits of hypofractionation and whether biological assumptions about the underlying alpha/beta ratio can translate into a true clinical advantage. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM azietman@partners.org NR 44 TC 15 Z9 15 U1 0 U2 3 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD SEP-OCT PY 2007 VL 13 IS 5 BP 295 EP 301 DI 10.1097/PPO.0b013e318156dbe3 PG 7 WC Oncology SC Oncology GA 218PN UT WOS:000250027500006 PM 17921728 ER PT J AU Kim, JH Dhanasekaran, SM Mehra, R Tomlins, SA Gu, W Yu, JJ Kumar-Sinha, C Cao, XH Dash, A Wang', L Ghosh, D Shedden, K Montie, JE Rubin, MA Pienta, KJ Shah, RB Chinnaiyan, AM AF Kim, Jung H. Dhanasekaran, Saravana M. Mehra, Rohit Tomlins, Scott A. Gu, Wenjuan Yu, Jianjun Kumar-Sinha, Chandan Cao, Xuhong Dash, Atreya Wang', Lei Ghosh, Debashis Shedden, Kerby Montie, James E. Rubin, Mark A. Pienta, Kenneth J. Shah, Rajal B. Chinnaiyan, Arul M. TI Integrative analysis of genomic aberrations associated with prostate cancer progression SO CANCER RESEARCH LA English DT Article ID COPY NUMBER ALTERATIONS; GENE-EXPRESSION; CDNA MICROARRAYS; ARRAY CGH; HYBRIDIZATION; RESOLUTION; DNA; AMPLIFICATION; TUMORS; PATTERNS AB Integrative analysis of genomic aberrations in the context of trancriptomic alterations will lead to a more comprehensive perspective on prostate cancer progression. Genome-wide copy number changes were monitored using array comparative genomic hybridization of laser-capture microdissected prostate cancer samples spanning stages of prostate cancer progression, including precursor lesions, clinically localized disease, and metastatic disease. A total of 62 specific cell populations from 38 patients were profiled. Minimal common regions (MCR) of alterations were defined for each sample type, and metastatic samples displayed the most number of alterations. Clinically localized prostate cancer samples with high Gleason grade resembled metastatic samples with respect to the size of altered regions and number of affected genes. A total of 9 out of 13 MCRs in the putative precursor lesion, high-grade prostatic intraepithelial neoplasia (PIN), showed an overlap with prostate cancer cases (amplifications in 3q29, 5q31.3-q32, 6q27, and 8q24.3 and deletions in 6q22.31, 16p 12.2, 17q21.2, and 17q21.31), whereas postatrophic hyperplasia (PAH) did not exhibit this overlap. Interestingly, prostate cancers that do not overexpress ETS family members (i.e., gene fusion-negative prostate cancers) harbor differential aberrations in 1q23, 6q16, 6q21, 10q23, and 10q24. Integrative analysis with matched mRNA profiles identified genetic alterations in several proposed candidate genes implicated in prostate cancer progression. C1 Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Biostat, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Stat, Ann Arbor, MI USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Program Bioinformat, Ann Arbor, MI USA. Tata Mem Hosp, Adv Ctr Treatment Res & Educ Canc, Bombay, Maharashtra, India. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pathol, Boston, MA 02115 USA. RP Chinnaiyan, AM (reprint author), Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Dept Pathol, Ann Arbor, MI 48109 USA. EM arul@uinich.edu RI Pienta, Kenneth/E-7679-2015; OI Pienta, Kenneth/0000-0002-4138-2186; Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [PC040517, P50 CA69568, PC051081, R01 CA102872, R01 CA97063, U01 CA111275] NR 48 TC 72 Z9 77 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2007 VL 67 IS 17 BP 8229 EP 8239 DI 10.1158/0008-5472.CAN-07-1297 PG 11 WC Oncology SC Oncology GA 209RW UT WOS:000249406700041 PM 17804737 ER PT J AU Ogino, S Hazra, A Tranah, GJ Kirkner, GJ Kawasaki, T Nosho, K Ohnishi, M Suemoto, Y Meyerhardt, JA Hunter, DJ Fuchs, CS AF Ogino, Shuji Hazra, Aditi Tranah, Gregory J. Kirkner, Gregory J. Kawasaki, Takako Nosho, Katsuhiko Ohnishi, Mutsuko Suemoto, Yuko Meyerhardt, Jeffrey A. Hunter, David J. Fuchs, Charles S. TI MGMT germline polymorphism is associated with somatic MGMT promoter methylation and gene silencing in colorectal cancer SO CARCINOGENESIS LA English DT Article ID O-6-METHYLGUANINE DNA METHYLTRANSFERASE; A-T TRANSITIONS; MICROSATELLITE INSTABILITY; ALKYLTRANSFERASE ACTIVITY; PHENOTYPE CIMP; NURSES HEALTH; G-C; RISK; REPAIR; CELLS AB O-6-methylguanine-DNA methyltransferase (MGMT) repairs inappropriately methylated guanine residues in DNA. MGMT promoter methylation and gene silencing are common events in colorectal cancer, and may or may not co-exist with the CpG island methylator phenotype (CIMP). To date, no study has examined the relationship between MGMT promoter methylation and common MGMT single nucleotide polymorphisms (SNPs), which have been associated with colorectal cancer risk. Utilizing real-time polymerase chain reaction (MethyLight technology), we quantified DNA methylation in MGMT and eight other markers (a CIMP diagnostic panel including CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1 in 182 colorectal cancers collected from two prospective cohorts, the Nurses' Health Study and the Health Professionals Follow-up Study. We genotyped four MGMT germline SNPs in normal DNA and assessed microsatellite instability (MSI), 18q loss of heterozygosity and KRAS and BRAF status in tumors. The presence of a common MGMT promoter SNP (NM_002412.2:c.-56C > T) (rs16906252) was strongly associated with MGMT methylation (multivariate odds ratio 18.0; 95% confidence interval, 6.2-52.1, P < 0.0001). The presence of the c.-56C > T SNP was also associated with loss of MGMT expression in tumors (assessed by immunohistochemistry) (P = 0.009). This promoter SNP was not correlated with KRAS, BRAF, CIMP or MSI status. None of the other three non-promoter SNPs was significantly associated with any molecular changes tested. In conclusion, we have found a strong association between the germline polymorphism (c.-56C > T) of the MGMT promoter and promoter methylation/silencing of MGMT in colorectal cancer. Our data provide compelling evidence for common susceptibility for MGMT promoter CpG island methylation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Calif Pacific Med Ctr, San Francisco, CA 94107 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. RP Ogino, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA87969, U54 CA100971, P01 CA55075] NR 43 TC 63 Z9 65 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2007 VL 28 IS 9 BP 1985 EP 1990 DI 10.1093/carcin/bgm160 PG 6 WC Oncology SC Oncology GA 227RU UT WOS:000250676300019 PM 17621591 ER PT J AU Nowak, J Weylandt, KH Habbel, P Wang, J Dignass, A Glickman, JN Kang, JX AF Nowak, Johannes Weylandt, Karsten H. Habbel, Piet Wang, Jingdong Dignass, Axel Glickman, Jonathan N. Kang, Jing X. TI Colitis-associated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids SO CARCINOGENESIS LA English DT Article ID DEXTRAN SODIUM-SULFATE; COLORECTAL ADENOMAS; FAT-1 MICE; CARCINOGENESIS; AZOXYMETHANE; CANCER; CHEMOPREVENTION; CELECOXIB; OMEGA-3-FATTY-ACIDS; INFLAMMATION AB Colorectal cancer (CRC) is the second leading cause of cancer deaths in USA. Anti-inflammatory drugs were shown to be effective in the prevention of CRC, supporting a link between inflammation and tumorigenesis in the colon. However, due to their side effects, long-term administration of these drugs for CRC prevention is not feasible. An increased tissue content of omega-3 polyunsaturated fatty acids (n-3 PUFA) can dampen colon inflammation in animals as well as in humans. Whether increasing colon tissue n-3 PUFA alone is effective in preventing colon tumorigenesis remains to be investigated. Here we show that endogenously increased tissue levels of n-3 PUFA in the fat-1 transgenic mouse model lower incidence and growth rate of colon tumors induced by inflammation (dextrane sodium sulfate) plus treatment with carcinogen (azoxymethane). This was accompanied by lower activity of nuclear factor kappa B (NF-kappa B), higher expression of transforming growth factor beta in the colons and lower expression of inducible nitric oxide synthase in the tumors of fat-1 animals. Our data provide new insight into the mechanism by which n-3 PUFA suppresses tumorigenesis through dampening of inflammation and NF-kappa B activity. These results support a protective role of n-3 PUFA supplementation in the prevention of CRC. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Charite Univ Med Berlin, Dept Gastroenterol, D-13353 Berlin, Germany. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, 149-13th St,Room 4433, Boston, MA 02129 USA. EM jxkang@partners.org FU NCI NIH HHS [R01CA-113605] NR 30 TC 63 Z9 67 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2007 VL 28 IS 9 BP 1991 EP 1995 DI 10.1093/carcin/bgm166 PG 5 WC Oncology SC Oncology GA 227RU UT WOS:000250676300020 PM 17634405 ER PT J AU Mendelson, K Aikawa, E Mettler, BA Sales, V Martin, D Mayer, JE Schoen, FJ AF Mendelson, Karen Aikawa, Elena Mettler, Bret A. Sales, Virna Martin, David Mayer, John E. Schoen, Frederick J. TI Healing and remodeling of bioengineered pulmonary artery patches implanted in sheep SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE cells; vascular wall healing; vascular remodeling; vascular graft; pulmonary artery; scaffold; tissue engineering; wound healing ID ENDOTHELIAL PROGENITOR CELLS; STEM-CELLS; TISSUE; VIVO AB Purpose: We hypothesized that cell-seeded patches implanted into sheep pulmonary artery would undergo progressive and complete healing into a viable structure well integrated with the arterial wall. Methods: Autologous ovine blood-derived endothelial progenitor cells (EPCs) and bone marrow-derived mesenchymal stem cells (MSCs) were isolated and cultured in vitro. MSCs and EPCs were seeded onto poly-4-hydroxybutyrate (P4HB)-coated polyglycolic acid (PGA) nonwoven biodegradable mesh scaffolds (10x20 mm) and cultured for 5 days in a laminar fluid flow system. Seeded patches were implanted into the wall of sheep pulmonary artery for 1-2 weeks (n=4) or 4-6 weeks (n=3). Preimplant and postexplant specimens were analyzed by histology and immunohistochermstry. Results: Unimplanted constructs contained alpha-smooth muscle actin (SMA)-positive cells and early extracellular matrix formation (primarily glycosaminoglycans). One week after implantation, seeded patches had surface thrombus formation and macrophage infiltration. Seeded patches implanted for 2 weeks showed granulation tissue, early pannus formation, macrophages, foreign body giant cells around disintegrating polymer, and early angiogenesis (microvessel formation). After 4 weeks in vivo, seeded patches contained glycosaminoglycans, collagen, and coverage of the luminal surface by host artery-derived pannus containing alpha-SMA-positive cells and laminated elastin; polymer scaffold degradation was almost complete with replacement by fibrous tissue containing viable cells. Conclusions: This study shows that cell-seeded patches implanted in sheep pulmonary artery remodel to layered and viable tissue well integrated into the native arterial wall. The key remodeling processes included (1) intimal overgrowth at the luminal surface (pannus formation; neointima) and (2) granulation tissue formation and fibrosis with foreign body reaction. (C) 2007 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiovasc Surg, Boston, MA 02115 USA. Tepha Inc, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA USA. RP Schoen, FJ (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM fschoen@partners.org NR 19 TC 19 Z9 23 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD SEP-OCT PY 2007 VL 16 IS 5 BP 277 EP 282 DI 10.1016/j.carpath.2007.03.008 PG 6 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 218OX UT WOS:000250025900004 PM 17868878 ER PT J AU Jaff, M Dake, M Pornpa, J Ansel, G Yoder, T AF Jaff, Michael Dake, Michael Pornpa, Jeffrey Ansel, Gary Yoder, Tony TI Standardized evaluation and reporting of Stent fractures in clinical trials of noncoronary devices SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE peripheral vascular disease; complications adult cath/intervention; trauma ID SUPERFICIAL FEMORAL-ARTERY; DISEASE AB Objectives: Define the prospective surveillance and reporting parameters for assessment of metallic stents used in clinical trials of superficial femoral artery atherosclerosis. Background: While advances in medical therapies to improve atherosclerotic risk factor profiles in patients with peripheral arterial disease have focused on prevention of disease progression, the development of endovascular devices is altering the therapeutic algorithm for patients with peripheral arterial disease. Stents have emerged as one of the advances that may promote durable patency, particularly in the infrainguinal arteries. Methods: The Zilver-PTX is a prospective multicenter randomized trial of bare metal versus drug-eluting nitinol stents for superficial femoral artery peripheral arterial disease. A predefined surveillance program is mandated in this trial. During the genesis of this program, it became clear that no single standard has existed to identify, classify, and report fractures of metallic stents placed in peripheral arteries. Results: This report defines the key components of prospective stent fracture surveillance, including location of radiographic images obtained, types of radiographic equipment, methods of limb, and image intensifier positioning, intervals required for imaging, grading schemes for reporting, and methods of analyzing the images. Conclusions: As the proliferation of minimally invasive revascularization strategies continues, the stability of metallic endoprostheses is increasingly critical. Uniform surveillance of these devices for fracture and disarticulation is important in order to compare the relative merits of various stent-based devices in clinical trials. (C) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Div Cardiovasc Med, Sect Vasc Med, Boston, MA 02114 USA. Univ Virginia, Charlottesville, VA USA. St Elizabeths Med Ctr, Dept Cardiol, Boston, MA USA. Riverside Methodist Hosp, Columbus, OH 43214 USA. Inst Med, Bloomington, IN USA. RP Jaff, M (reprint author), 55 Fruit St,Yawkey 5938, Boston, MA USA. EM docmrjaff@aol.com NR 5 TC 47 Z9 48 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP 1 PY 2007 VL 70 IS 3 BP 460 EP 462 DI 10.1002/ccd.21240 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 207EA UT WOS:000249233200022 PM 17559108 ER PT J AU Schainfeld, RM AF Schainfeld, Robert M. TI Primetime for a shave and haircut? SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Sect Vasc Med, Boston, MA 02114 USA. RP Schainfeld, RM (reprint author), Massachusetts Gen Hosp, Sect Vasc Med, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP 1 PY 2007 VL 70 IS 3 BP 467 EP 468 DI 10.1002/cccl.21320 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 207EA UT WOS:000249233200024 PM 17721927 ER PT J AU White, CJ Cates, CU Cowley, MJ Weiner, BH Carpenter, JS Hopkins, LN Jaff, MR Ramee, SR Rymer, MM Wholey, MH AF White, Christopher J. Cates, Christopher U. Cowley, Michael J. Weiner, Bonnie H. Carpenter, Jeffrey S. Hopkins, L. Nelson Jaff, Michael R. Ramee, Stephen R. Rymer, Marilyn M. Wholey, Mark H. TI Interventional stroke therapy: Current state of the art and needs assessment SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE peripheral vascular disease (PVD); stroke; thrombolytic ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; RANDOMIZED CONTROLLED-TRIAL; MECHANICAL THROMBECTOMY; STENT PLACEMENT; MERCI TRIAL; PART I; OUTCOMES; RECOMMENDATIONS; THROMBOLYSIS AB The primary therapeutic strategy for ischemic stroke, as for MI patients, is early reperfusion. Improvement in stroke treatment will require dedicated stroke centers to emulate MI quality indicators such as minimizing the "door-to-balloon time". A critical element in achieving this goal will be organizing the existing multidisciplinary pool of carotid interventionalists to provide the endovascular component of the acute care for ischemic stroke patients. (C) 2007 Wiley-Liss, Inc. C1 Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. Virginia Commonwealth Univ, Med Coll Virginia, Div Cardiol, Richmond, VA 23298 USA. St Vincent Hosp, Fallon Clin, Worcester, MA 01604 USA. W Virginia Univ, Dept Radiol, Morgantown, WV 26506 USA. SUNY Buffalo, Toshiba Stroke Res Ctr, Buffalo, NY 14260 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Lukes Hosp, Mid Amer Brain & Stroke Inst, Kansas City, MO USA. Univ Pittsburgh, Pittsburgh Vasc Inst, Pittsburgh, PA USA. RP White, CJ (reprint author), Alton Ochsner Med Fdn & Ochsner Clin, 1516 Jefferson Highway, New Orleans, LA 70121 USA. EM cwhite@ochsner.org RI White, Christopher/J-6686-2012; bashzar, salman/R-5748-2016 OI White, Christopher/0000-0001-8618-7539; NR 30 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP 1 PY 2007 VL 70 IS 3 BP 471 EP 476 DI 10.1002/ccd.21336 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 207EA UT WOS:000249233200027 PM 17721987 ER PT J AU Matsumoto, M Pocai, A Rossetti, L DePinho, RA Accili, D AF Matsumoto, Michihiro Pocai, Alessandro Rossetti, Luciano DePinho, Ronald A. Accili, Domenico TI Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor foxo1 in liver SO CELL METABOLISM LA English DT Article ID FACTOR-BINDING PROTEIN-1; LIPOGENIC GENE-EXPRESSION; INSULIN-RECEPTOR; PHOSPHOENOLPYRUVATE CARBOXYKINASE; CAENORHABDITIS-ELEGANS; COACTIVATOR PGC-1; LIPID-METABOLISM; KNOCKOUT MICE; RAT-LIVER; IN-VIVO AB The hallmark of type 2 diabetes is excessive hepatic glucose production. Several transcription factors and coactivators regulate this process in cultured cells. But gene ablation experiments have yielded few clues as to the physiologic mediators of this process in vivo. We show that inactivation of the gene encoding forkhead protein Foxo1 in mouse liver results in 40% reduction of glucose levels at birth and 30% reduction in adult mice after a 48 hr fast. Gene expression and glucose clamp studies demonstrate that Foxo1 ablation impairs fasting- and cAMP-induced glycogenolysis; and gluconeogenesis. Pgcl alpha is unable to induce gluconeogenesis in Foxol-deficient hepatocytes, while the cAMP response is significantly blunted. Conversely, Foxol deletion in liver curtails excessive glucose production caused by generalized ablation of insulin receptors and prevents neonatal diabetes and hepatosteatosis in insulin receptor knockout mice. The data provide a unifying mechanism for regulation of hepatic glucose production by cAMP and insulin. C1 Columbia Univ, Coll Phys & Surg, Dept Med, Naomi Berrie Diabet Ctr, New York, NY 10032 USA. Albert Einstein Coll Med, Diabet Res Ctr, Dept Med, Bronx, NY 10461 USA. Albert Einstein Coll Med, Diabet Res Ctr, Dept Mol Pharmacol, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Ctr,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Ctr,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Ctr,Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA. RP Accili, D (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, Naomi Berrie Diabet Ctr, New York, NY 10032 USA. EM da230@columbia.edu FU NIDDK NIH HHS [DK57539, DK63068] NR 51 TC 251 Z9 256 U1 4 U2 25 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD SEP PY 2007 VL 6 IS 3 BP 208 EP 216 DI 10.1016/i.cmet.2007.08.006 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 207XV UT WOS:000249285300009 PM 17767907 ER PT J AU Lensch, MW Schlaeger, TM Zon, LI Daley, GQ AF Lensch, M. William Schlaeger, Thorsten M. Zon, Leonard I. Daley, George Q. TI Teratoma formation assays with human embryonic stem cells: A rationale for one type of human-animal chimera SO CELL STEM CELL LA English DT Article ID HUMAN BLASTOCYSTS; CARCINOMA-CELLS; REPLACE NEURONS; MOUSE EMBRYOS; LINE; DIFFERENTIATION; BRAIN; INVITRO; FETAL; OLIGODENDROCYTES AB Despite a long and valuable history, human-animal chimera research has often been questioned. Among the moral issues raised by chimeras is the concept that integration of human cells into anatomical locations such as the brain might endow animals with "human-like" capacities including self-awareness. We present a justification for one type of human-animal chimera experiment: the evaluation of hES cell developmental potency via teratoma, formation in immunodeficient mice. We argue that this experiment raises no significant moral concerns and should be the jurisdiction of animal care and use committees and exempt from formal review by the stem cell research oversight process. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Stem Cell Inst, Cambridge, MA 02138 USA. Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU Howard Hughes Medical Institute NR 49 TC 80 Z9 81 U1 0 U2 9 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 PY 2007 VL 1 IS 3 BP 253 EP 258 DI 10.1016/j.stem.2007.07.019 PG 6 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XT UT WOS:000251055200007 PM 18371359 ER PT J AU Purton, LE Scadden, DT AF Purton, Louise E. Scadden, David T. TI Limiting factors in murine hematopoietic stem cell assays SO CELL STEM CELL LA English DT Review ID BONE-MARROW CELLS; SELF-RENEWAL CAPACITY; IN-VIVO; C-KIT; COMPETITIVE REPOPULATION; RADIATION SENSITIVITY; PROGENITOR CELLS; IRRADIATED MICE; MOUSE; EXPRESSION AB Hematopoiesis arguably provides the most well-defined role of stem cells in tissue development, maintenance, and repair, largely because of the experimental methods developed over decades of investigation. Assays of hematopoietic stem and progenitor cell potential were developed in the late 1950s-1960s with the first reports of in vivo transplantation into lethally irradiated recipients (Ford et al., 1956; McCulloch and Till, 1960) and clonal growth of hematopoietic bone marrow cells in vitro (Bradley and Metcalf, 1966). These two major assays have undergone substantial refinement but remain the foundation for defining hematopoietic stem cell biology. Here, we provide a brief overview of methods commonly used to analyze hematopoietic stem and progenitor cell content in mice, discuss the limitations of these assays, and provide an in-depth review of the limiting dilution assay (Szilvassy et al., 1990), the best single assay for quantitating HSC content. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Purton, LE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Harvard Stem Cell Inst, Boston, MA 02114 USA. EM lpurton@partners.org NR 66 TC 126 Z9 130 U1 1 U2 14 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 PY 2007 VL 1 IS 3 BP 263 EP 270 DI 10.1016/j.stem.2007.08.016 PG 8 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XT UT WOS:000251055200009 PM 18371361 ER PT J AU Jude, CD Climer, L Xu, D Artinger, E Fisher, JK Ernst, P AF Jude, Craig D. Climer, Leslie Xu, Diyong Artinger, Erika Fisher, Jill K. Ernst, Patricia TI Unique and independent roles for MLL in adult hematopoietic stem cells and progenitors SO CELL STEM CELL LA English DT Article ID HISTONE METHYLTRANSFERASE COMPLEX; GENE-EXPRESSION PROFILE; ACUTE MYELOID-LEUKEMIA; PROTO-ONCOPROTEIN MLL; DROSOPHILA-TRITHORAX; EPIGENETIC INHERITANCE; MUTANT MICE; BONE-MARROW; FUSION GENE; FAMILY AB The Mixed Lineage Leukemia (MLL) gene is essential for embryonic hematopoietic stem cell (HSC) development, but its role during adult hematopoiesis is unknown. Using an inducible knockout model, we demonstrate that Mll is essential for the maintenance of adult HSCs and progenitors, with fatal bone marrow failure occurring within 3 weeks of Mll deletion. Mll-deficient cells are selectively lost from mixed bone marrow chimeras, demonstrating their failure to self-renew even in an intact bone marrow environment. Surprisingly, HSCs lacking MY exhibit ectopic cell-cycle entry, resulting in the depletion of quiescent HSCs. In contrast, Mll deletion in myelo-erythroid progenitors results in reduced proliferation and reduced response to cytokine-induced cell-cycle entry. Committed lymphoid and myeloid cells no longer require Mll, defining the early multipotent stages of hematopoiesis as Mll dependent. These studies demonstrate that Mll plays selective and independent roles within the hematopoietic system, maintaining quiescence in HSCs and promoting proliferation in progenitors. C1 Dartmouth Med Sch, Dept Genet, Hanover, NH 03755 USA. Dartmouth Med Sch, Norris Cotton Canc Ctr, Hanover, NH 03755 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Ernst, P (reprint author), Dartmouth Med Sch, Dept Genet, 725 Remsen,HB7400, Hanover, NH 03755 USA. EM patricia.ernst@dartmouth.edu FU NCRR NIH HHS [P20 RR016437]; NHLBI NIH HHS [R01 HL090036, R01 HL090036-01A2]; NIAID NIH HHS [R01 AI051427]; NIDDK NIH HHS [DK067119, K01 DK067119, K01 DK067119-04] NR 52 TC 154 Z9 157 U1 1 U2 2 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 PY 2007 VL 1 IS 3 BP 324 EP 337 DI 10.1016/j.stem.2007.05.019 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XT UT WOS:000251055200014 PM 18371366 ER PT J AU Kim, K Ng, K Rugg-Gunn, PJ Shieh, JH Kirak, O Jaenisch, R Wakayama, T Moore, MA Pedersen, RA Daley, GQ AF Kim, Kitai Ng, Kitwa Rugg-Gunn, Peter J. Shieh, Jae-Hung Kirak, Oktay Jaenisch, Rudolf Wakayama, Teruhiko Moore, Malcolm A. Pedersen, Roger A. Daley, George Q. TI Recombination signatures distinguish embryonic stem cells derived by parthenogenesis and somatic cell nuclear transfer SO CELL STEM CELL LA English DT Article ID HUMAN OOCYTES; MOUSE OOCYTES; GENOME; LINES; INSTABILITY; GENE; DNA; ESTABLISHMENT; METHYLATION; INHIBITION AB Parthenogenesis and somatic cell nuclear transfer (SCNT) are two methods for deriving embryonic stem (ES) cells that are genetically matched to the oocyte donor or somatic cell donor, respectively. Using genome-wide single nucleotide polymorphism (SNP) analysis, we demonstrate distinct signatures of genetic recombination that distinguish parthenogenetic ES cells from those generated by SCNT. We applied SNP analysis to the human ES cell line SCNT-hES-1, previously claimed to have been derived by SCNT, and present evidence that it represents a human parthenogenetic ES cell line. Genome-wide SNP analysis represents a means to validate the genetic provenance of an ES cell line. C1 Childrens Hosp, Div Pediat Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Stem Cell Inst, Boston, MA 02115 USA. Univ Cambridge, Dept Surg, Cambridge CB2 2XY, England. Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 2XY, England. Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RIKEN Kobe, Ctr Dev Biol, Kobe, Hyogo 6500047, Japan. RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu RI Kirak, Oktay/H-6347-2013 OI Kirak, Oktay/0000-0002-6524-4685 FU Medical Research Council [G0300723, G0600275] NR 33 TC 85 Z9 87 U1 2 U2 10 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 PY 2007 VL 1 IS 3 BP 346 EP 352 DI 10.1016/j.stem.2007.07.001 PG 7 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XT UT WOS:000251055200016 PM 18371368 ER PT J AU Wall, DM Nadeau, WJ Pazos, MA Shi, HN Galyov, EE McCormick, BA AF Wall, Daniel M. Nadeau, William J. Pazos, Michael A. Shi, Hai Ning Galyov, Edouard E. McCormick, Beth A. TI Identification of the Salmonella enterica serotype Typhimurium SipA domain responsible for inducing neutrophil recruitment across the intestinal epithelium SO CELLULAR MICROBIOLOGY LA English DT Article ID SEROVAR TYPHIMURIUM; INVASIVE SALMONELLA; ESCHERICHIA-COLI; EUKARYOTIC CELLS; PROTEIN SIPA; ACTIN; SECRETION; EXPRESSION; MIGRATION; BINDING AB In human intestinal disease induced by Salmonella enterica serotype Typhimurium (S. typhimurium) transepithelial migration of polymorphonuclear leukocytes (PMNs) rapidly follows attachment of the bacteria to the epithelial apical membrane. Previously, we have shown that the S. typhimurium effector protein, SipA, plays a pivotal role in signalling epithelial cell responses that lead to the transepithelial migration of PMNs. Thus, the objective of this study was to determine the functional domain of SipA that regulates this signalling event. SipA was divided into two fragments: the SipAb C-terminal fragment(426-684) (259 AA), which binds actin, and the SipAa fragment(2-425) (424 AA), which a role has yet to be described. In both in vitro and in vivo models of S. typhimurium-induced intestinal inflammation the SipAa fragment exhibited a profound ability to induce PMN transmigration, whereas the SipAb actin-binding domain failed to induce PMN transmigration. Subsequent mapping of the SipAa domain identified a 131-amino-acid region (SipAa3(294-424)) responsible for modulating PMN transepithelial migration. Interestingly, neither intracellular translocation nor actin association of SipA was necessary for its ability to induce PMN transepithelial migration. As these results indicate SipA has at least two separate functional domains, we speculate that during infection S. typhimurium requires delivery of SipA to both extracellular and intracellular spaces to maximize pro-inflammatory responses and mechanisms of bacterial invasion. C1 Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Mucosal Immun Lab, Charlestown, MA 02129 USA. Harvard Med Sch, Dept Microbiol & Mol Genet, Boston, MA 02129 USA. Inst Anim Hlth, Div Microbiol, Compton, Berks, England. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Mucosal Immun Lab, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu FU Biotechnology and Biological Sciences Research Council [D18830]; NIDDK NIH HHS [DK 56754, DK 33506] NR 45 TC 33 Z9 34 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD SEP PY 2007 VL 9 IS 9 BP 2299 EP 2313 DI 10.1111/j.1462-5822.2007.00960.x PG 15 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 198ZS UT WOS:000248666600018 PM 17697195 ER PT J AU Jett, JR Schild, SE Keith, RL Kesler, KA AF Jett, Janws R. Schild, Steven E. Keith, Robert L. Kesler, Kenneth A. TI Treatment of non-small cell lung cancer, stage IIIB - ACCP evidence-based clinical practice guidelines (2nd edition) SO CHEST LA English DT Article DE chemoradiotherapy; hyperfractionated radiotherapy; radiotherapy; treatment stage IIIB ID SUPERIOR VENA-CAVA; PALLIATIVE RADIOTHERAPY; PHASE-III; RANDOMIZED-TRIAL; 2 FRACTIONS; SEQUENTIAL CHEMORADIOTHERAPY; ACCELERATED RADIOTHERAPY; BRONCHOGENIC-CARCINOMA; THORACIC RADIOTHERAPY; PROGNOSTIC-FACTORS AB Objective: To develop evidence-based guidelines on best available treatment options for patients with stage IIIB non-small cell lung cancer (NSCLC). Methods: A review was conducted of published English-language (abstract or full text) phase H or phase III trials and guidelines from other organizations that address management of the various categories of stage IIIB disease. The literature search was provided by the Duke University Center for Clinical Health Policy Research and supplemented by any additional studies known by the authors. Results: Surgery may be indicated for carefully selected patients with T4N0-1M0. Patients with N3 nodal involvement are not considered to be surgical candidates. For individuals with unresectable disease, good performance score, and minimal weight loss, treatment with combined chemoradiotherapy results in better survival than radiotherapy (RT) alone. Concurrent chemoradiotherapy seems to be associated with improved survival compared with sequential chemoradiotherapy. Multiple daily fractions of RT when combined with chemotherapy have not been shown to result in improved survival compared with standard once-daily RT combined with chemotherapy. The optimal chemotherapy agents and the number of cycles of treatment to combine with RT are uncertain. Conclusion: Prospective trials are needed to answer important questions, such as the role of induction therapy in patients with potentially resectable stage IIIB disease. Future trials are needed to answer the questions of optimal chemotherapy agents and radiation fractionation schedule. The role of targeted novel agents in combination with chemoradiotherapy is just starting to be investigated. C1 Mayo Clin, Div Pulm Med & Med Oncol, Rochester, MN 55905 USA. Mayo Clin, Dept Radiat Oncol, Scottsdale, AZ USA. Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. Indiana Univ, Sch Med, Div Thorac Surg, Indianapolis, IN 46204 USA. RP Jett, JR (reprint author), Mayo Clin, Div Pulm Med & Med Oncol, 200 1st St SW, Rochester, MN 55905 USA. EM JETT.JAMES@mayo.edu OI schild, steven/0000-0002-2850-4126 NR 52 TC 78 Z9 79 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2007 VL 132 IS 3 SU S BP 266S EP 276S DI 10.1378/chest.07-1380 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 216OZ UT WOS:000249889400018 PM 17873173 ER PT J AU Griffin, JP Koch, KA Nelson, JE Cooley, ME AF Griffin, John P. Koch, Kathryn A. Nelson, Judith E. Cooley, Mary E. TI Palliative care consultation, quality-of-life measurements, and bereavement for end-of-life care in patients with lung cancer - ACCP evidence-based clinical practice guidelines (2nd edition) SO CHEST LA English DT Review DE bereavement; cultural competence; end-of-life care; lung cancer; palliative care consultation; quality-of-life measurements ID RANDOMIZED CONTROLLED-TRIAL; ADULTS RECEIVING TREATMENT; SYMPTOM DISTRESS; FUNCTIONAL ASSESSMENT; COMPLICATED GRIEF; PHYSICIAN COMMUNICATION; QUESTIONNAIRE QLQ-C30; AMBULATORY ONCOLOGY; MEDICAL RECORDS; NURSES GRIEF AB Objective: To develop clinical practice guidelines for application of palliative care consultation, quality-of-life measurements, and appropriate bereavement activities for patients with lung cancer. Methods: To review the pertinent medical literature on palliative care consultation, quality-of-life measurements, and bereavement for patients with lung cancer, developing multidisciplinary discussions with authorities in these areas, and evolving written guidelines for end-of-life care of these patients. Results: Palliative care consultation has developed into a new specialty with credentialing of experts in this field based on extensive experience with patients in end-of-life circumstances including those with lung cancer. Bereavement studies of the physical and emotional morbidity of family members and caregivers before, during, and after the death of a cancer patient have supported truthful communication, consideration of psychological problems, effective palliative care, understanding of the patient's spiritual and cultural background, and sufficient forewarning of impending death. Conclusion: Multidisciplinary investigations and experiences, with emphasis on consultation and delivery of palliative care, timely use of quality-of-life measurements for morbidities of treatment modalities and prognosis, and an understanding of the multifaceted complexities of the bereavement process, have clarified additional responsibilities of the attending physician. C1 Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Div Pulm Crit Care & Sleep Med, Memphis, TN 38163 USA. Univ Florida, Hlth Sci Ctr, Dept Internal Med, Jacksonville, FL 32209 USA. Univ Florida, Hlth Sci Ctr, Div Pulm & Crit Care Med, Jacksonville, FL 32209 USA. Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. Dana Farber Canc Inst, Ctr Res Nursing & Patient Care, Boston, MA 02115 USA. RP Griffin, JP (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Med, 956 Court Ave,Room H314, Memphis, TN 38163 USA. EM jpgriffin@utmem.edu NR 195 TC 32 Z9 37 U1 3 U2 8 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2007 VL 132 IS 3 SU S BP 404S EP 422S DI 10.1378/chest.07-1392 PG 19 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 216OZ UT WOS:000249889400027 PM 17873182 ER PT J AU Shapiro, S Hill, NS AF Shapiro, Shelley Hill, Nicholas S. TI Transition from IV to subcutaneous prostacyclin: Premature withdrawal? SO CHEST LA English DT Editorial Material ID PULMONARY-ARTERIAL-HYPERTENSION; TREPROSTINIL; EPOPROSTENOL; BOSENTAN; INFUSION C1 Univ Calif Los Angeles, Sch Med, Greater Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. RP Shapiro, S (reprint author), Univ Calif Los Angeles, Sch Med, Greater Los Angeles VA Med Ctr, 11301 Wilshire Blvd,Cardiol Sect 111e, Los Angeles, CA 90073 USA. EM Shelley.Shapiro@va.gov NR 7 TC 6 Z9 6 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2007 VL 132 IS 3 BP 741 EP 743 DI 10.1378/chest.07-1992 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 214MN UT WOS:000249742100002 PM 17873184 ER PT J AU Reddy, RD Keshavan, MS Yao, JK AF Reddy, Ravinder D. Keshavan, Matcherl S. Yao, JeffTey K. TI Reduced platelet serotonergic responsivity as assessed by dense granule secretion in first-episode psychosis SO CLINICAL BIOCHEMISTRY LA English DT Article DE platelets; dense granule secretion; serotonin; schizophrenia; mood disorder ID SCHIZOPHRENIA; ACTIVATION AB Objectives: To determine whether blunted serotonergic responsivity, indicated by decreased platelet dense granule secretion (DGS), occurs in neuroleptic-naive patients with schizophrenia, as observed previously in chronic schizophrenia. Design and methods: Serotonin (5-HT)-amplified DGS was examined in 40 first-episode neuroleptic-naive patients (24 with schizophrenia and 16 with mood disorders) and 24 healthy subjects. Results: Healthy controls showed robustly increased DGS. Schizophrenic patients showed very modest DGS increases; mood disorder patients showed inten-nediate response. Conclusions: Blunted DGS appears to a characteristic of schizophrenia that is observed in the treatment-naive condition. (C) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlthcare Syst, Pittsburgh, PA 15206 USA. Wayne State Univ, Detroit, MI 48201 USA. Univ Pittsburgh, Sch Med, Dept Pharm, Pittsburgh, PA 15213 USA. RP Reddy, RD (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. EM reddyr@upme.edu FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [M01 RR000056, M01 RR00056]; NIMH NIH HHS [MH-46118, K08 MH064118-01A1, K08 MH064118-02, K08 MH064118-03, K08 MH064118-04, K08 MH064118-05, MH-45203, MH-58141, MH45156, P50 MH045156, R01 MH058141, R01 MH058141-01A2, R01 MH058141-02, R01 MH058141-03, R01 MH058141-04, R01 MH058141-05, R01 MH060902, R01 MH060902-01A2, R01 MH060902-02, R01 MH060902-03, R01 MH060902-04, R01 MH060902-05] NR 10 TC 1 Z9 2 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD SEP PY 2007 VL 40 IS 13-14 BP 1081 EP 1083 DI 10.1016/j.clinbiochem.2007.04.019 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 209XV UT WOS:000249422200027 PM 17601524 ER PT J AU Shields, HM Shaffer, K O'Farrell, RP Travers, R Hayward, JN Becker, LS Lauwers, GY AF Shields, Helen M. Shaffer, Kitt O'Farrell, Richard P. Travers, Robin Hayward, Jane N. Becker, Laren S. Lauwers, Gregory Y. TI Gastrointestinal manifestations of dermatologic disorders SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Review ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; MAST-CELL DISEASE; ENDOTHELIAL GROWTH-FACTOR; AMERICAN JOINT COMMITTEE; C-KIT MUTATION; SYSTEMIC MASTOCYTOSIS; EPIDERMOLYSIS-BULLOSA; MALIGNANT-MELANOMA; GERMLINE MUTATION; CUTANEOUS MASTOCYTOSIS AB The skin and the gastrointestinal tract may be affected concurrently by the same diseases. Pathogenetically, these conditions may be primarily dermatologic diseases involving the gastrointestinal (GI) tract or systemic diseases involving the skin, GI tract, and liver simultaneously. The correct diagnosis of such conditions relies on the ability of the gastroenterologist to recognize the underlying dermatologic disorder. The goal of this clinical review article is to increase gastroenterologists' awareness and understanding of some of these conditions. Case vignettes are presented and the relevant literature reviewed for epidermolysis bullosa, mastocytosis, hereditary hemorrhagic telangiectasia, and melanoma. This review focuses on increasing gastroenterologists' ability to recognize, diagnose, comprehend, and manage patients with these dermatologic conditions who have GI manifestations. Advances in molecular genetics that provide insight into the underlying pathophysiology and histopathology of these lesions are highlighted. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol Cambridge Hlth Alliance, Somerville, MA USA. Skincare Associates, Chestnut Hill, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Shields, HM (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM hshields@bidmc.harvard.edu OI Shaffer, Kitt/0000-0001-6488-6988 NR 96 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2007 VL 5 IS 9 DI 10.1016/j.cgh.2007.05.018 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 213CB UT WOS:000249642400004 ER PT J AU Weisbord, SD Fried, LF Mor, MK Resnick, AL Unruh, ML Palevsky, PM Levenson, DJ Cooksey, SH Fine, MJ Kimmel, PL Arnold, RM AF Weisbord, Steven D. Fried, Linda F. Mor, Maria K. Resnick, Abby L. Unruh, Mark L. Palevsky, Paul M. Levenson, David J. Cooksey, Stephen H. Fine, Michael J. Kimmel, Paul L. Arnold, Robert M. TI Renal provider recognition of symptoms in patients on maintenance hemodialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID QUALITY-OF-LIFE; SPIRITUAL BELIEFS; MINI-COG; DISEASE; DIALYSIS; PAIN; DEPRESSION; SEVERITY; PREVALENCE; SAMPLE AB Background and Objectives: Although several studies have found that the burden of symptoms in patients who are on maintenance hemodialysis is substantial, little is known about renal providers' awareness of these symptoms. The aim of this study was to assess renal provider recognition of symptoms and their severity, in hemodialysis patients. Design, Setting, Participants, & Measurements: The Dialysis Symptom Index, a 30-item measure of symptoms and their severity was administered to patients during a routine hemodialysis session. Immediately after surveying patients, the renal provider who evaluated the patient completed the Dialysis Symptom Index to report the symptoms that he or she believed were present in that patient. Sensitivity, specificity, and positive and negative predictive values of provider reports of symptoms were calculated using patient reports as the reference standard. Patient-provider agreement on the presence and severity of symptoms was assessed using the K statistic. Results: Surveys were completed by 75 patients and 18 providers. For 27 of 30 symptoms, the sensitivity of provider responses was < 50%, and provider responses for 25 symptoms were characterized by positive predictive values of < 75%. K scores for 25 symptoms including those pertaining to pain, sexual dysfunction, sleep disturbance, and psychologic distress were < 0.20, indicating poor provider recognition of these symptoms. Providers underestimated the severity of 19 of 30 symptoms. Conclusions: Renal providers are largely unaware of the presence and severity of symptoms in patients who are on maintenance hemodialysis. Implementation of a standardized symptom assessment process may improve provider recognition of symptoms and promote use of symptom-alleviating treatments. C1 VA Pittsburgh Healthcare Syst, Med Special Serv Line, Renal Sect, Pittsburgh, PA 15240 USA. VA Pittsburgh Healthcare Syst, Med Special Serv Line, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Med Special Serv Line, Renal Sect, Mailstop 111F-U,7E Room 120, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu FU NCATS NIH HHS [UL1 TR000005]; NIAID NIH HHS [K24 AI001769] NR 34 TC 72 Z9 75 U1 1 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2007 VL 2 IS 5 BP 960 EP 967 DI 10.2215/CJN.00990207 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 204JJ UT WOS:000249039500016 PM 17702730 ER EF