FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lo Sardo, V Zuccato, C Gaudenzi, G Vitali, B Ramos, C Tartari, M Myre, MA Walker, JA Pistocchi, A Conti, L Valenza, M Drung, B Schmidt, B Gusella, J Zeitlin, S Cotelli, F Cattaneo, E AF Lo Sardo, Valentina Zuccato, Chiara Gaudenzi, Germano Vitali, Barbara Ramos, Catarina Tartari, Marzia Myre, Michael A. Walker, James A. Pistocchi, Anna Conti, Luciano Valenza, Marta Drung, Binia Schmidt, Boris Gusella, James Zeitlin, Scott Cotelli, Franco Cattaneo, Elena TI An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin SO NATURE NEUROSCIENCE LA English DT Article ID WILD-TYPE HUNTINGTIN; DISEASE GENE HOMOLOG; EMBRYONIC STEM-CELLS; N-CADHERIN CLEAVAGE; MUTANT HUNTINGTIN; TARGETED DISRUPTION; LACKING HUNTINGTIN; ADAM10; MICE; ZEBRAFISH AB The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role is obscure. We studied neurulation in htt-null embryonic stem cells and htt-morpholino zebrafish embryos and found a previously unknown, evolutionarily recent function for this ancient protein. We found that htt was essential for homotypic interactions between neuroepithelial cells; it permitted neurulation and rosette formation by regulating metalloprotease ADAM 10 activity and Ncadherin cleavage. This function was embedded in the N terminus of htt and was phenocopied by treatment of htt knockdown zebrafish with an ADAM 10 inhibitor. Notably, in htt-null cells, reversion of the rosetteless phenotype occurred only with expression of evolutionarily recent htt heterologues from deuterostome organisms. Conversely, all of the heterologues that we tested, including htt from Drosophila melanogaster and Dictyostelium discoideum, exhibited anti-apoptotic activity. Thus, anti-apoptosis may have been one of htt's ancestral function(s), but, in deuterostomes, htt evolved to acquire a unique regulatory activity for controlling neural adhesion via ADAM10-Ncadherin, with implications for brain evolution and development. C1 [Lo Sardo, Valentina; Zuccato, Chiara; Vitali, Barbara; Ramos, Catarina; Tartari, Marzia; Conti, Luciano; Valenza, Marta; Cattaneo, Elena] Univ Milan, Dept Pharmacol Sci, Milan, Italy. [Lo Sardo, Valentina; Zuccato, Chiara; Vitali, Barbara; Ramos, Catarina; Tartari, Marzia; Conti, Luciano; Valenza, Marta; Cattaneo, Elena] Univ Milan, Ctr Stem Cell Res, Milan, Italy. [Gaudenzi, Germano; Pistocchi, Anna; Cotelli, Franco] Univ Milan, Dept Biol, Milan, Italy. [Myre, Michael A.; Walker, James A.; Gusella, James] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Drung, Binia; Schmidt, Boris] Tech Univ Darmstadt, Clemens Schopf Inst Chem & Biochem, Darmstadt, Germany. [Zeitlin, Scott] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA. RP Cattaneo, E (reprint author), Univ Milan, Dept Pharmacol Sci, Milan, Italy. EM elena.cattaneo@unimi.it RI Conti, Luciano/H-4184-2012; Pistocchi, Anna /A-6228-2014; gaudenzi, Germano/H-4705-2014; Schmidt, Boris/D-3293-2009; OI Conti, Luciano/0000-0002-2050-9846; Pistocchi, Anna /0000-0001-9467-2542; Schmidt, Boris/0000-0003-1662-2392; CATTANEO, ELENA/0000-0002-0755-4917; ZUCCATO, CHIARA/0000-0003-1771-3392; VALENZA, MARTA/0000-0002-7048-9257 FU Huntington's Disease Society of America Coalition for the Cure; Italian Telethon Foundation [GGP06250]; Ministero dell'Istruzione, dell'Universita e della Ricerca Scientifica, Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale [2006052993]; Fundacao para a Ciencia e Tecnologia through University of Porto [SERH/BD/9627/2002]; [NS16367] FX We thank M. MacDonald (Massachusetts General Hospital) for the Hdh+/+ and Hdhex4-5 cells, P. Saftig for the ADAM 10 antibody (University of Kiel), E. Ruthazer for the zebrafish Ncadherin antibody (McGill University), F. Gardoni and E. Marcello for helpful technical advice on the use of ADAM 10 and SAP97 antibodies, A. Badaloni for help with subcloning, and G. Simonutti for assistance with initial imaging analysis. This work has progressed at a very slow pace because it was mostly unfunded. In the beginning, this work was partially supported by the Huntington's Disease Society of America Coalition for the Cure (2007-2009) and by Italian Telethon Foundation (GGP06250, 2007-2009). Some additional support was provided by the Ministero dell'Istruzione, dell'Universita e della Ricerca Scientifica, Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale (2006052993, 2006). Since 2009, progress of this work has relied entirely on occasional donations. We wish to thank one donor that in 2009 collected a considerable amount of small donations for us to continue this work and another donor that has been following our progress for 10 years. C.A. was supported by the Fundacao para a Ciencia e Tecnologia (grant number SERH/BD/9627/2002) through the GABBA Programme (University of Porto). E.C., J.G. and S.Z. were members of the Huntington's Disease Society of America Coalition for the Cure and J.G. received support from NS16367. NR 48 TC 31 Z9 31 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2012 VL 15 IS 5 BP 713 EP 721 DI 10.1038/nn.3080 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 932DI UT WOS:000303270200015 PM 22466506 ER PT J AU Marusyk, A Almendro, V Polyak, K AF Marusyk, Andriy Almendro, Vanessa Polyak, Kornelia TI Intra-tumour heterogeneity: a looking glass for cancer? SO NATURE REVIEWS CANCER LA English DT Review ID BREAST-CANCER; CLONAL EVOLUTION; GENE-EXPRESSION; ESOPHAGEAL ADENOCARCINOMA; NONGENETIC HETEROGENEITY; LYMPHOBLASTIC-LEUKEMIA; DISTANT METASTASIS; BARRETTS-ESOPHAGUS; DRUG-RESISTANCE; LUNG-CANCER AB Populations of tumour cells display remarkable variability in almost every discernable phenotypic trait, including clinically important phenotypes such as ability to seed metastases and to survive therapy. This phenotypic diversity results from the integration of both genetic and non-genetic influences. Recent technological advances have improved the molecular understanding of cancers and the identification of targets for therapeutic interventions. However, it has become exceedingly apparent that the utility of profiles based on the analysis of tumours en masse is limited by intra-tumour genetic and epigenetic heterogeneity, as characteristics of the most abundant cell type might not necessarily predict the properties of mixed populations. In this Review, we discuss both genetic and non-genetic causes of phenotypic heterogeneity of tumour cells, with an emphasis on heritable phenotypes that serve as a substrate for clonal selection. We discuss the implications of intra-tumour heterogeneity in diagnostics and the development of therapeutic resistance. C1 [Marusyk, Andriy; Almendro, Vanessa; Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Marusyk, Andriy; Almendro, Vanessa; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Almendro, Vanessa] Inst Invest Biomed August Pi & Sunyer, Hosp Clin, Dept Med Oncol, Barcelona 08036, Spain. RP Polyak, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM Kornelia_Polyak@dfci.harvard.edu FU US Army Congressionally Directed Research [W81XWH-07-1-0294, BC087579]; US National Cancer Institute [PO1 CA80111]; Susan G. Komen Foundation; Breast Cancer Research Foundation; Cellex Foundation FX We thank members of our laboratory and F. Michor and S. Itzkovitz for their critical reading of our manuscript and for stimulating discussions. Tumour diversity research in the authors' laboratory is supported by US Army Congressionally Directed Research W81XWH-07-1-0294 (K. P.) and BC087579 (A. M.), US National Cancer Institute PO1 CA80111 (K. P.), Susan G. Komen Foundation (K. P.), Breast Cancer Research Foundation (K. P.) and the Cellex Foundation (V.A.). NR 107 TC 512 Z9 525 U1 23 U2 206 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAY PY 2012 VL 12 IS 5 BP 323 EP 334 DI 10.1038/nrc3261 PG 12 WC Oncology SC Oncology GA 930VM UT WOS:000303170100011 PM 22513401 ER PT J AU Flaherty, KT Hodi, FS Fisher, DE AF Flaherty, Keith T. Hodi, F. Stephen Fisher, David E. TI From genes to drugs: targeted strategies for melanoma SO NATURE REVIEWS CANCER LA English DT Review ID COLONY-STIMULATING FACTOR; TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; PHASE-II TRIAL; FIBROBLAST-GROWTH-FACTOR; COMPARATIVE GENOMIC HYBRIDIZATION; METASTATIC MALIGNANT-MELANOMA; PRIMARY CUTANEOUS MELANOMA; CELL-CYCLE ARREST; MHC CLASS-I AB The past decade has revealed that melanoma is comprised of multiple subclasses that can be categorized on the basis of key features, including the clinical stage of disease, the oncogenic molecular 'drivers', the anatomical location or the behaviour of the primary lesion and the expression of specific biomarkers. Although exercises in subclassification are not new in oncology, progress in this area has produced both conceptual and clinical breakthroughs, which, for melanoma, are unprecedented in the modern history of the disease. This Review focuses on these recent striking advances in the strategy of molecularly targeted approaches to the therapy of melanoma in humans. C1 [Flaherty, Keith T.; Fisher, David E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM dfisher3@partners.org NR 192 TC 152 Z9 155 U1 8 U2 55 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAY PY 2012 VL 12 IS 5 BP 349 EP 361 DI 10.1038/nrc3218 PG 13 WC Oncology SC Oncology GA 930VM UT WOS:000303170100013 PM 22475929 ER PT J AU Vakoc, BJ Fukumura, D Jain, RK Bouma, BE AF Vakoc, Benjamin J. Fukumura, Dai Jain, Rakesh K. Bouma, Brett E. TI Cancer imaging by optical coherence tomography: preclinical progress and clinical potential SO NATURE REVIEWS CANCER LA English DT Review ID GREEN FLUORESCENT PROTEIN; IN-VIVO; ANTIANGIOGENIC THERAPY; PHOTODYNAMIC THERAPY; GLIOBLASTOMA PATIENTS; ANGIOGENESIS; MICROSCOPY; BIOMARKERS; VIABILITY; SURVIVAL AB The past decade has seen dramatic technological advances in the field of optical coherence tomography (OCT) imaging. These advances have driven commercialization and clinical adoption in ophthalmology, cardiology and gastrointestinal cancer screening. Recently, an array of OCT-based imaging tools that have been developed for preclinical intravital cancer imaging applications has yielded exciting new capabilities to probe and to monitor cancer progression and response in vivo. Here, we review these results, forecast the future of OCT for preclinical cancer imaging and discuss its exciting potential to translate to the clinic as a tool for monitoring cancer therapy. C1 [Vakoc, Benjamin J.; Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Vakoc, Benjamin J.; Bouma, Brett E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Vakoc, Benjamin J.; Fukumura, Dai; Jain, Rakesh K.; Bouma, Brett E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vakoc, Benjamin J.; Bouma, Brett E.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02142 USA. [Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. RP Vakoc, BJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM vakoc.benjamin@mgh.harvard.edu FU US National Institutes of Health [5K25CA127465, P01-CA080124, R01-CA126642, R01-CA096915, S10-RR027070]; Federal Share Income Grant; Department of Defense [W81XWH-10-1-0016]; Center for Biomedical OCT Research and Translation [P41EB015903]; National Center for Research Resources; National Institute of Biomedical Imaging and Bioengineering of the US National Institutes of Health FX US National Institutes of Health grants 5K25CA127465 (to B. J. V.), P01-CA080124 (to R. K. J. and D. F.), R01-CA126642 (to R. K. J.), R01-CA096915 (to D. F.), S10-RR027070 (to D. F.), a Federal Share Income Grant (to R. K. J. and D. F.), and Department of Defense Breast Cancer Research Innovator Award W81XWH-10-1-0016 (to R. K. J.). This project was supported by the Center for Biomedical OCT Research and Translation through Grant Number P41EB015903, awarded by the National Center for Research Resources and the National Institute of Biomedical Imaging and Bioengineering of the US National Institutes of Health. NR 49 TC 96 Z9 99 U1 7 U2 47 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAY PY 2012 VL 12 IS 5 BP 363 EP 368 DI 10.1038/nrc3235 PG 6 WC Oncology SC Oncology GA 930VM UT WOS:000303170100014 PM 22475930 ER PT J AU Tanzi, R AF Tanzi, Rudolph TI WHAT ARE GENETIC STUDIES TEACHING US ABOUT HOW TO TREAT ALZHEIMER'S DISEASE? SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 12th International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy CY MAY 09-12, 2012 CL Stockholm, SWEDEN C1 [Tanzi, Rudolph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. EM tanzi@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY PY 2012 VL 33 SU 1 MA 79 BP S34 EP S34 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 930NX UT WOS:000303147200080 ER PT J AU Touroutoglou, A Hollenbeck, M Dickerson, BC Barrett, LF AF Touroutoglou, Alexandra Hollenbeck, Mark Dickerson, Bradford C. Barrett, Lisa Feldman TI Dissociable large-scale networks anchored in the right anterior insula subserve affective experience and attention SO NEUROIMAGE LA English DT Article DE Dorsal anterior insula; Ventral anterior insula; Intrinsic functional connectivity; Individual differences; Attention; Processing speed; Affective experience ID INTRINSIC FUNCTIONAL CONNECTIVITY; RESTING HUMAN BRAIN; OLD-WORLD MONKEY; MEMORY PERFORMANCE; PREFRONTAL CORTEX; CINGULATE CORTEX; COGNITIVE CONTROL; DEFAULT NETWORK; HUMAN AWARENESS; WORKING-MEMORY AB Meta-analytic summaries of neuroimaging studies point to at least two major functional-anatomic subdivisions within the anterior insula that contribute to the detection and processing of salient information: a dorsal region that is routinely active during attention tasks and a ventral region that is routinely active during affective experience. In two independent samples of cognitively normal human adults, we used intrinsic functional connectivity magnetic resonance imaging to demonstrate that the right dorsal and right ventral anterior insula are nodes in separable large-scale functional networks. Furthermore, stronger intrinsic connectivity within the right dorsal anterior insula network was associated with better performance on a task involving attention and processing speed whereas stronger connectivity within the right ventral anterior insula network was associated with more intense affective experience. These results support the hypothesis that the identification and manipulation of salient information is subserved by at least two brain networks anchored in the right anterior insula that exhibit distinct large-scale topography and dissociable behavioral correlates. (C) 2012 Elsevier Inc. All rights reserved. C1 [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Touroutoglou, Alexandra; Hollenbeck, Mark; Dickerson, Bradford C.; Barrett, Lisa Feldman] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Touroutoglou, Alexandra; Hollenbeck, Mark; Dickerson, Bradford C.; Barrett, Lisa Feldman] Harvard Univ, Sch Med, Charlestown, MA USA. [Touroutoglou, Alexandra; Hollenbeck, Mark; Dickerson, Bradford C.; Barrett, Lisa Feldman] Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Charlestown, MA USA. [Hollenbeck, Mark; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hollenbeck, Mark; Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, 253 Nightingale Hall, Boston, MA 02115 USA. EM l.barrett@neu.edu FU National Institutes of Health [DP1OD003312]; National Institute on Aging [AG030311, AG029840]; National Center For Research Resources [1S10RR023401, 1S10RR019307, 1S10RR023043] FX We thank Randy Buckner for providing the data used in the analysis of Sample 1 and the preprocessing/rs-fcMRI tools and Rebecca Dautoff for assistance. This work was supported by the National Institutes of Health Director's Pioneer Award (DP1OD003312) to Lisa Feldman Barrett, a National Institute on Aging grant (AG030311) to Lisa Feldman Barrett, a National Institute on Aging grant (AG029840) to Brad Dickerson, and the Shared Instrumentation Grants (1S10RR023401, 1S10RR019307, and 1S10RR023043) from the National Center For Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources, the National Institutes of Health, or the National Institute on Aging. NR 87 TC 65 Z9 65 U1 2 U2 18 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 MAY 1 PY 2012 VL 60 IS 4 BP 1947 EP 1958 DI 10.1016/j.neuroimage.2012.02.012 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 927RA UT WOS:000302926600003 PM 22361166 ER PT J AU Dobromyslin, VI Salat, DH Fortier, CB Leritz, EC Beckmann, CF Milberg, WP McGlinchey, RE AF Dobromyslin, Vitaly I. Salat, David H. Fortier, Catherine B. Leritz, Elizabeth C. Beckmann, Christian F. Milberg, William P. McGlinchey, Regina E. TI Distinct functional networks within the cerebellum and their relation to cortical systems assessed with independent component analysis SO NEUROIMAGE LA English DT Article DE Cerebellar networks; Functional connectivity; fcMRI; ICA ID COGNITIVE-AFFECTIVE SYNDROME; INFERIOR PARIETAL LOBULE; RESTING-STATE NETWORKS; HUMAN BRAIN; PREFRONTAL CORTEX; MOTOR CORTEX; CONNECTIVITY; FLUCTUATIONS; PROJECTIONS; PRIMATE AB Cerebellar functional circuitry has been examined in several prior studies using resting fMRI data and seed-based procedures, as well as whole-brain independent component analysis (ICA). Here, we hypothesized that ICA applied to functional data from the cerebellum exclusively would provide increased sensitivity for detecting cerebellar networks compared to previous approaches. Consistency of group-level networks was assessed in two age- and sex-matched groups of twenty-five subjects each. Cerebellum-only ICA was compared to the traditional whole-brain ICA procedure to examine the potential gain in sensitivity of the novel method. In addition to replicating a number of previously identified cerebellar networks, the current approach revealed at least one network component that was not apparent with the application of whole brain ICA. These results demonstrate the gain in sensitivity attained through specifying the cerebellum as a target structure with regard to the identification of robust and reliable networks. The use of similar procedures could be important in further expanding on previously defined patterns of cerebellar functional anatomy, as well as provide information about unique networks that have not been explored in prior work. Such information may prove crucial for understanding the cognitive and behavioral importance of the cerebellum in health and disease. Published by Elsevier Inc. C1 [Dobromyslin, Vitaly I.; Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Ctr Vet, Boston, MA USA. [Salat, David H.; Leritz, Elizabeth C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Fortier, Catherine B.; Milberg, William P.; McGlinchey, Regina E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Fortier, Catherine B.; Leritz, Elizabeth C.; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Leritz, Elizabeth C.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Beckmann, Christian F.] Radboud Univ Nijmegen, Donders Inst, Ctr Cognit Neuroimaging, Nijmegen, Netherlands. [Beckmann, Christian F.] Univ Twente, MIRA Inst, Enschede, Netherlands. [Beckmann, Christian F.] Oxford Ctr Funct MRI Brain FMRIB, Oxford, England. RP McGlinchey, RE (reprint author), 150 S Huntington Ave,GRECC 182 JP, Boston, MA 02130 USA. EM regina_mcglinchey@hms.harvard.edu RI Beckmann, Christian/E-6374-2012; McGlinchey, Regina/R-1971-2016 FU National Institutes of Health; National Institute of Nursing Research [R01 NR 010827]; National Institute of Neurological Disease and Stroke [K23NS062148]; National Institute on Aging [K23AG034258]; Veterans Administration Merit Service; VA Rehabilitation Research and Development Service TBI Center of Excellence; National Institute of Alcoholism and Alcohol Abuse [R01 14205] FX This work was supported by grants from the National Institutes of Health, including National Institute of Alcoholism and Alcohol Abuse (R01 14205 to RM); National Institute of Nursing Research (R01 NR 010827 to DS); National Institute of Neurological Disease and Stroke (K23NS062148 to EL) and the National Institute on Aging (K23AG034258 to CF). Additionally, this work was supported by the Veterans Administration Merit Service Award to RM and by the VA Rehabilitation Research and Development Service TBI Center of Excellence to RM and WM. NR 44 TC 16 Z9 16 U1 3 U2 11 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 MAY 1 PY 2012 VL 60 IS 4 BP 2073 EP 2085 DI 10.1016/j.neuroimage.2012.01.139 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 927RA UT WOS:000302926600016 PM 22342804 ER PT J AU Gibson, CJ Joffe, H Bromberger, JT Thurston, RC Lewis, TT Khalil, N Matthews, KA AF Gibson, Carolyn J. Joffe, Hadine Bromberger, Joyce T. Thurston, Rebecca C. Lewis, Tene T. Khalil, Naila Matthews, Karen A. TI Mood Symptoms After Natural Menopause and Hysterectomy With and Without Bilateral Oophorectomy Among Women in Midlife SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HEALTH AB OBJECTIVE: To examine whether mood symptoms increased more for women in the years after hysterectomy with or without bilateral oophorectomy relative to natural menopause. METHODS: Using data from the Study of Women's Health Across the Nation (n=1,970), depression and anxiety symptoms were assessed annually for up to 10 years with the Center for Epidemiological Studies Depression Index and four anxiety questions, respectively. Piece-wise hierarchical growth models were used to relate natural menopause, hysterectomy with ovarian conservation, and hysterectomy with bilateral oophorectomy to trajectories of mood symptoms before and after the final menstrual period or surgery. Covariates included educational attainment, race, menopausal status, age the year before final menstrual period or surgery, and time-varying body mass index, self-rated health, hormone therapy, and antidepressant use. RESULTS: By the tenth annual visit, 1,793 (90.9%) women reached natural menopause, 76 (3.9%) reported hysterectomy with ovarian conservation, and 101 (5.2%) reported hysterectomy with bilateral oophorectomy. For all women, depressive and anxiety symptoms decreased in the years after final menstrual period or surgery. These trajectories did not significantly differ by hysterectomy or oophorectomy status. The Center for Epidemiological Studies Depression Index means were 0.72 standard deviations lower and anxiety symptoms were 0.67 standard deviations lower 5 years after final menstrual period or surgery. CONCLUSION: In this study, mood symptoms continued to improve after the final menstrual period or hysterectomy for all women. Women who undergo a hysterectomy with or without bilateral oophorectomy in midlife do not experience more negative mood symptoms in the years after surgery. C1 [Gibson, Carolyn J.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Wright State Univ, Dept Community Hlth, Kettering, OH USA. RP Gibson, CJ (reprint author), Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15213 USA. EM gibsoncj@upmc.edu FU National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA); National Institute of Nursing Research (NINR); NIH Office of Research on Women's Health (ORWH) [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495]; Bayer HealthCare Pharmaceuticals FX SWAN has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women's Health (ORWH) (Grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH or the NIH.; Dr. Joffe has received research support from Bayer HealthCare Pharmaceuticals and has performed advisory and consulting work for Sanofi-Aventis/Sunovion, Pfizer, and Noven. The other authors did not report any potential conflicts of interest. NR 15 TC 14 Z9 14 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2012 VL 119 IS 5 BP 935 EP 941 DI 10.1097/AOG.0b013e31824f9c14 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 930OW UT WOS:000303150000008 PM 22525904 ER PT J AU Tracy, EE Konstantopoulos, WM AF Tracy, Erin E. Konstantopoulos, Wendy Macias TI Human Trafficking A Call for Heightened Awareness and Advocacy by Obstetrician-Gynecologists SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID SEX TRAFFICKING C1 [Tracy, Erin E.; Konstantopoulos, Wendy Macias] Massachusetts Gen Hosp, Boston, MA 02180 USA. RP Tracy, EE (reprint author), Massachusetts Gen Hosp, Founders 406,Fruit St, Boston, MA 02180 USA. EM EETracy@partners.org NR 15 TC 2 Z9 2 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2012 VL 119 IS 5 BP 1045 EP 1047 DI 10.1097/AOG.0b013e31824f9aaa PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 930OW UT WOS:000303150000022 PM 22525917 ER PT J AU Platts-Mills, TF Hunold, KM Bortsov, AV Soward, AC Peak, DA Jones, JS Swor, RA Lee, DC Domeier, RM Hendry, PL Rathlev, NK McLean, SA AF Platts-Mills, Timothy F. Hunold, Katie M. Bortsov, Andrey V. Soward, April C. Peak, David A. Jones, Jeffrey S. Swor, Robert A. Lee, David C. Domeier, Robert M. Hendry, Phyllis L. Rathlev, Niels K. McLean, Samuel A. TI More educated emergency department patients are less likely to receive opioids for acute pain SO PAIN LA English DT Article DE Emergency medicine; Pain; Socioeconomic factors ID ETHNIC DISPARITIES; NECK PAIN; INADEQUATE EMERGENCY; SOCIOECONOMIC-STATUS; ANALGESIC TREATMENT; HEALTH BEHAVIORS; RISK-FACTORS; CARE; WHIPLASH; EXPERIENCES AB Inadequate treatment of pain in United States emergency departments (EDs) is common, in part because of the limited and idiosyncratic use of opioids by emergency providers. This study sought to determine the relationship between patient socioeconomic characteristics and the likelihood that they would receive opioids during a pain-related ED visit. We conducted a cross-sectional analysis of ED data obtained as part of a multicenter study of outcomes after minor motor vehicle collision (MVC). Study patients were non-Hispanic white patients between the ages of 18 and 65 years who were evaluated and discharged home from 1 of 8 EDs in 4 states. Socioeconomic characteristics include educational attainment and income. Of 690 enrolled patients, the majority had moderate or severe pain (80%). Patients with higher education attainment had lower levels of pain, pain catastrophizing, perceived life threat, and distress. More educated patients were also less likely to receive opioids during their ED visit. Opioids were given to 54% of patients who did not complete high school vs 10% of patients with post-college education (chi(2) test P < .001). Differences in the frequency of opioid administration between patients with the lowest educational attainment (39%, 95% confidence interval 22% to 60%) and highest educational attainment (13%, 95% confidence interval 7% to 23%) remained after adjustment for age, sex, income, and pain severity (P = .01). In this sample of post-MVC ED patients, more educated patients were less likely to receive opioids. Further study is needed to assess the generalizability of these findings and to determine the reason for the difference. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved. C1 [Platts-Mills, Timothy F.; Hunold, Katie M.; Bortsov, Andrey V.; Soward, April C.; McLean, Samuel A.] Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC 27599 USA. [Platts-Mills, Timothy F.; McLean, Samuel A.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC 27599 USA. [Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Jones, Jeffrey S.] Dept Emergency Med, Grand Rapids, MI USA. [Swor, Robert A.] William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48072 USA. [Lee, David C.] N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY USA. [Domeier, Robert M.] St Joseph Mercy Hosp, Dept Emergency Med, Ann Arbor, MI 48104 USA. [Hendry, Phyllis L.] Univ Florida, Dept Emergency Med & Pediat, Jacksonville, FL USA. [Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. RP Platts-Mills, TF (reprint author), Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC 27599 USA. EM tplattsm@med.unc.edu OI McLean, Samuel/0000-0001-9482-3582 FU National Institute of Arthritis, Musculoskeletal, and Skin Diseases [R01 AR056328]; National Center for Research Resources [UL1RR025747] FX Funding for this study was provided by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases (R01 AR056328:Samuel A. McLean) and the National Center for Research Resources Award Number UL1RR025747 (Timothy F. Platts-Mills). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 43 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAY PY 2012 VL 153 IS 5 BP 967 EP 973 DI 10.1016/j.pain.2012.01.013 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 928PW UT WOS:000302996200009 PM 22386895 ER PT J AU As-Sanie, S Harris, RE Napadow, V Kim, J Neshewat, G Kairys, A Williams, D Clauw, DJ Schmidt-Wilcke, T AF As-Sanie, Sawsan Harris, Richard E. Napadow, Vitaly Kim, Jieun Neshewat, Gina Kairys, Anson Williams, David Clauw, Daniel J. Schmidt-Wilcke, Tobias TI Changes in regional gray matter volume in women with chronic pelvic pain: A voxel-based morphometry study SO PAIN LA English DT Article DE Chronic pelvic pain; Endometriosis; Voxel-based morphometry; Thalamus; Cingulate cortex ID FIBROMYALGIA PATIENTS; IMAGING EVIDENCE; ENDOMETRIOSIS; BRAIN; OSTEOARTHRITIS; STIMULATION; PERFORMANCE; LAPAROSCOPY; HEADACHE; SURGERY AB Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15%-20% of women in the United States. Endometriosis is often associated with CPP, however, other factors, such as preexisting or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing. Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, and 23 healthy controls. All patients with endometriosis and/or CPP were surgically confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception, including the left thalamus, left cingulate gyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis who had no CPP. We conclude that CPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved. C1 [Schmidt-Wilcke, Tobias] Univ Tubingen, Hertie Inst klin Hirnforsch, Dept Neurol, D-72076 Tubingen, Germany. [As-Sanie, Sawsan; Neshewat, Gina] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Harris, Richard E.; Kairys, Anson; Williams, David; Clauw, Daniel J.; Schmidt-Wilcke, Tobias] Univ Michigan, Chron Pain & Fatigue Res Ctr, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Napadow, Vitaly; Kim, Jieun] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. RP Schmidt-Wilcke, T (reprint author), Univ Tubingen, Hertie Inst klin Hirnforsch, Dept Neurol, D-72076 Tubingen, Germany. EM tobias.schmidt-wilcke@med.uni-tuebingen.de FU Pfizer; NIH Building Interdisciplinary Research in Women's Health [K12HD001438, NIH UL1RR024986]; Bayer [NIH R01-AR050044]; DAMD [17-00-2-0018]; DFG (Deutsche Forschungsgemeinschaft [GZ: SchM 2665/1-1]; Dana Foundation; Department of Defense [DAMD-W81XWH-07-2-0050]; NCCAM, NIH [R01-AT004714, P01-AT002048] FX D.J. Clauw declares associations with the following companies: Cypress Bioscience, Eli Lilly and Company, Forest Laboratories, Pierre Fabre Medicament, Pfizer, Procter & Gamble, Novu, Jazz, Johnson and Johnson, Merck, and Wyeth Pharmaceuticals. See the article online for full details of these relationships. The other authors declare no competing interests. R. E. Harris has received consulting fees and grant support from Pfizer.; This work was supported in part by the following research grants: NIH Building Interdisciplinary Research in Women's Health K12HD001438, NIH UL1RR024986; Bayer Droegemueller Award in Clinical Research, NIH R01-AR050044, and DAMD 17-00-2-0018. Tobias Schmidt-Wilcke is currently supported by a grant from the DFG (Deutsche Forschungsgemeinschaft, GZ: SchM 2665/1-1). Richard Harris is supported by grants from the Dana Foundation and the Department of Defense (Army Grant: DAMD-W81XWH-07-2-0050). Vitaly Napadow and Jieun Kim were supported by NCCAM, NIH (R01-AT004714 [Napadow], P01-AT002048 [Rosen]). NR 47 TC 52 Z9 56 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAY PY 2012 VL 153 IS 5 BP 1006 EP 1014 DI 10.1016/j.pain.2012.01.032 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 928PW UT WOS:000302996200014 PM 22387096 ER PT J AU Phillip, M Danne, T Shalitin, S Buckingham, B Laffel, L Tamborlane, W Battelino, T AF Phillip, Moshe Danne, Thomas Shalitin, Shlomit Buckingham, Bruce Laffel, Lori Tamborlane, William Battelino, Tadej CA Consensus Forum Participants TI Use of continuous glucose monitoring in children and adolescents SO PEDIATRIC DIABETES LA English DT Article ID QUALITY-OF-LIFE; TYPE-1 DIABETES-MELLITUS; INSULIN-PUMP THERAPY; PREDICTIVE ALARM ALGORITHMS; RANDOMIZED CONTROLLED-TRIAL; IMPROVED METABOLIC-CONTROL; GLYCEMIC CONTROL; NOCTURNAL HYPOGLYCEMIA; FREESTYLE NAVIGATOR; PEDIATRIC-PATIENTS C1 [Phillip, Moshe; Shalitin, Shlomit] Schneider Childrens Med Ctr Israel, Jesse Z & Sara Lea Shafer Inst Endocrinol & Diabe, Petah Tiqwa, Israel. [Phillip, Moshe; Shalitin, Shlomit] Felsenstein Med Res Ctr, Mol Endocrinol & Diabet Lab, Petah Tiqwa, Israel. [Phillip, Moshe; Shalitin, Shlomit] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Danne, Thomas] Kinderkrankenhaus Bult, Diabet Zentrum Kinder & Jugendliche, Hannover, Germany. [Buckingham, Bruce] Stanford Univ, Stanford, CA 94305 USA. [Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02115 USA. [Tamborlane, William] Yale Univ, Sch Med, New Haven, CT USA. [Battelino, Tadej] Univ Childrens Hosp, Dept Pediat Endocrinol, Ljubljana, Slovenia. RP Phillip, M (reprint author), Schneider Childrens Med Ctr Israel, Natl Ctr Childhood Diabet, Jesse Z & Sara Lea Shafer Inst Endocrinol & Diabe, 14 Kaplan St, IL-49202 Petah Tiqwa, Israel. EM mosheph@post.tau.ac.il OI Battelino, Tadej/0000-0002-0273-4732 FU Medtronic; DexCom; Roche; Abbott; Insulet; Animas; Novo Nordisk; Sanofi-Aventis; Eli Lilly; Johnson Johnson; Lilly; Abbott Diabetes Care; Bayer Diabetes Care FX M. P. is a member of the board of CGM3, hold stocks in D-Medical and CGM3, consultant to D-Medical, Bristol Myers Squibb, AstraZeneca, and Physical Logic; M. P.'s institution received grants or support from Medtronic, DexCom, Roche, Abbott, Insulet, Animas, Novo Nordisk, Sanofi-Aventis, and Eli Lilly; and received honoraria and travel expenses from Sanofi-Aventis, Novo Nordisk, Bayer, and AstraZeneca.; T. D. received honoraria for speaking engagements from several companies involved in the diabetes field and has received grant support from these companies (Abbott, Sanofi-Aventis, Bayer, Roche, Johnson & Johnson, Lilly, Medtronic, DexCom, and Novo Nordisk) for the conduct of studies or scientific meetings.; B. B. serves on a Medical Advisory Board and received research support from Medtronic, DexCom, and Abbott Diabetes Care.; L. L. received grant support from Bayer Diabetes Care and is a consultant for Lilly, Sanofi-Aventis, Bristol Myers Squibb, AstraZeneca, Johnson & Johnson, and Menarini. NR 81 TC 41 Z9 43 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1399-543X EI 1399-5448 J9 PEDIATR DIABETES JI Pediatr. Diabetes PD MAY PY 2012 VL 13 IS 3 BP 215 EP 228 DI 10.1111/j.1399-5448.2011.00849.x PG 14 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 931DC UT WOS:000303194000001 PM 22284160 ER PT J AU Mehta, SN Schwartz, N Wood, JR Svoren, BM Laffel, LMB AF Mehta, Sanjeev N. Schwartz, Natalie Wood, Jamie R. Svoren, Britta M. Laffel, Lori M. B. TI Evaluation of 1,5-anhydroglucitol, hemoglobin A1c, and glucose levels in youth and young adults with type 1 diabetes and healthy controls SO PEDIATRIC DIABETES LA English DT Article DE 1; 5-anhydroglucitol; diabetes mellitus; glycosylated; hemoglobin A; pediatrics; type 1 ID MICROVASCULAR COMPLICATIONS; MELLITUS; GLYCOMARK(TM); 1,5-ANHYDRO-D-GLUCITOL; VARIABILITY; EXCURSIONS; REDUCTION; THRESHOLD; TRIAL; RISK AB Mehta SN, Schwartz N, Wood JR, Svoren BM, Laffel LMB. Evaluation of 1,5-anhydroglucitol, hemoglobin A1c, and glucose levels in youth and young adults with type 1 diabetes and healthy controls. Background and objective: Serum 1,5-anhydroglucitol (1,5-AG) is a marker of hyperglycemic excursions in adults with diabetes and hemoglobin A1c (HbA1c) < 8%. We compared 1,5-AG levels among youth and young adults with and without type 1 diabetes (T1D) and investigated the utility of 1,5-AG in the assessment of glycemic status in pediatric T1D. Methods: We compared 1,5-AG, HbA1c, and plasma glucose levels in 138 patients with T1D (duration =1 yr) and 136 healthy controls, aged 1030 yr. Within each group, we investigated associations between 1,5-AG and clinical characteristics, HbA1c and random plasma glucose. For patients with T1D, 1,5-AG was further analyzed according to HbA1c strata: <8, 89, and >9%. Results: Compared to controls, patients with T1D had higher HbA1c (8.5 +/- 1.6 vs. 5.1 +/- 0.4%, p < 0.0001), lower 1,5-AG (4.0 +/- 2.0 vs. 24.7 +/- 6.4 mu g/mL, p < 0.0001), and higher glucose (11.1 +/- 5.2 vs. 5.1 +/- 0.9 mmol/L, p < 0.0001). Males had higher 1,5-AG than females within patients (4.5 +/- 2.3 vs. 3.4 +/- 1.6 mu g/mL, p = 0.003) and controls (26.0 +/- 6.6 vs. 23.5 +/- 6.0 mu g/mL, p = 0.02). 1,5-AG was not correlated with glucose in either group. 1,5-AG was significantly correlated to HbA1c in patients, but not controls. For patients with HbA1c < 8%, 1,5-AG demonstrated the widest range and was not predicted by HbA1c; 1,5-AG levels were narrowly distributed among patients with HbA1c = 8%. Conclusions: Youth and young adults with T1D demonstrate similar 1,5-AG levels which are distinct from controls. 1,5-AG assessment may provide unique information beyond that provided by HbA1c in the mid-term assessment of glycemic control in young patients with T1D and HbA1c < 8%. C1 [Mehta, Sanjeev N.; Schwartz, Natalie; Laffel, Lori M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Wood, Jamie R.] Childrens Hosp Los Angeles, Ctr Diabet Endocrinol & Metab, Los Angeles, CA 90027 USA. [Svoren, Britta M.] Golisano Childrens Hosp, Div Pediat Endocrinol, Rochester, NY USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU National Institutes of Health [K12 DK63696]; Eli Lilly Foundation; Charles H. Hood Foundation; Maria Griffin Drury Pediatric Fund; Katherine Adler Astrove Youth Education Fund; Diabetes and Endocrinology Research Center [P30DK036836] FX This study was supported by the National Institutes of Health Training Grant in Pediatric Endocrinology (K12 DK63696), an Eli Lilly Foundation Fellowship Training Grant, the Charles H. Hood Foundation, the Maria Griffin Drury Pediatric Fund, the Katherine Adler Astrove Youth Education Fund, and the Diabetes and Endocrinology Research Center (P30DK036836). Portions of this manuscript were presented at the 69th Scientific Sessions of the American Diabetes Association (2009). NR 25 TC 5 Z9 5 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD MAY PY 2012 VL 13 IS 3 BP 278 EP 284 DI 10.1111/j.1399-5448.2011.00830.x PG 7 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 931DC UT WOS:000303194000009 PM 22060802 ER PT J AU Jostins, L Pickrell, JK MacArthur, DG Barrett, JC AF Jostins, Luke Pickrell, Joseph K. MacArthur, Daniel G. Barrett, Jeffrey C. TI Misuse of hierarchical linear models overstates the significance of a reported association between OXTR and prosociality SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter C1 [Jostins, Luke; Barrett, Jeffrey C.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. [Pickrell, Joseph K.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. RP Jostins, L (reprint author), Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. EM lj4@sanger.ac.uk OI Barrett, Jeffrey/0000-0002-1152-370X NR 5 TC 2 Z9 2 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 2012 VL 109 IS 18 BP E1048 EP E1048 DI 10.1073/pnas.1202539109 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 936PI UT WOS:000303602100001 PM 22499788 ER PT J AU Davis, LL Leon, AC Toscano, R Drebing, CE Ward, LC Parker, PE Kashner, TM Drake, RE AF Davis, Lori L. Leon, Andrew C. Toscano, Richard Drebing, Charles E. Ward, L. Charles Parker, Pamela E. Kashner, T. Michael Drake, Robert E. TI A Randomized Controlled Trial of Supported Employment Among Veterans With Posttraumatic Stress Disorder SO PSYCHIATRIC SERVICES LA English DT Article ID SEVERE MENTAL-ILLNESS; WORK THERAPY; OUTCOMES; DISABILITY; PEOPLE; SCALE; COMPENSATION AB Objective: Posttraumatic stress disorder (PTSD) is a potentially disabling mental illness that can cause occupational dysfunction. Although vocational rehabilitation is often prescribed for patients with PTSD, standard vocational services are far from adequate in helping them obtain and maintain competitive employment. This study is the first to examine the outcome of evidence-based supported employment for veterans with PTSD. Methods: Unemployed veterans with PTSD were randomly assigned to either individual placement and support (IFS) supported employment (N=42) or a Veterans Health Administration Vocational Rehabilitation Program (VRP) treatment as usual (N=43). Employment rates and occupational outcomes were followed for 12 months. Results: During the 12-month study, 76% of the IFS participants gained competitive employment, compared with 28% of the VRP participants (number needed to treat=2.07; chi(2)=19.84, df=1, p<.001). Veterans assigned to IPS also worked substantially more weeks than those assigned to VRP (42% versus 16% of the eligible weeks, respectively; Mann-Whitney z test p<.001) and earned higher 12-month income (meant+/-SD income of $9,264+/-$13,294 for IFS versus $2,601+/-$6,009 for VRP; Mann-Whitney z test p<.001) during the 12-month period. Conclusions: Veterans with PTSD who received IPS were 2.7 times more likely to gain competitive employment than those who received VRP. Because work is central to recovery, these results should assist stakeholders in planning improved services for veterans with PTSD. (Psychiatric Services 63:464-470, 2012; doi:10.1176/appi.ps.201100340) C1 [Davis, Lori L.; Toscano, Richard] Tuscaloosa Vet Affairs Med Ctr VAMC, Res & Dev Serv, Tuscaloosa, AL 35404 USA. [Ward, L. Charles] Tuscaloosa Vet Affairs Med Ctr VAMC, Psychol Serv, Tuscaloosa, AL 35404 USA. [Leon, Andrew C.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Drebing, Charles E.] Boston Univ, Sch Med, Dept Psychiat, Bedford, MA USA. [Drebing, Charles E.] Edith Nourse Rogers Mem Vet Hosp, New England Mental Illness Res Educ & Clin Ctr, Bedford, MA USA. [Parker, Pamela E.] VAMC, Mental Hlth Serv, Birmingham, AL USA. [Kashner, T. Michael] US Dept Vet Affairs, Off Acad Affiliat, Washington, DC USA. [Kashner, T. Michael] Loma Linda Univ, Sch Med, Loma Linda, CA USA. [Drake, Robert E.] Dartmouth Med Sch, Psychiat Res Ctr, Lebanon, NH USA. RP Davis, LL (reprint author), Tuscaloosa Vet Affairs Med Ctr VAMC, Res & Dev Serv, 3701 Loop Rd E, Tuscaloosa, AL 35404 USA. EM lori.davis@va.gov RI Schueter, nicos/A-3625-2014 FU VA Rehabilitation Research and Development grant [D4092i]; Tuscaloosa VAMC's Research and Development Services; AstraZeneca FX This project was funded by VA Rehabilitation Research and Development grant D4092i and is registered at www.ClinicalTrials.gov (identifier number NCT00333801). The authors acknowledge the generous support of the Tuscaloosa VAMC's Research and Development Services and the hard work and devotion of the vocational rehabilitation specialists involved in the study, especially Allen Riley, M.A. The authors acknowledge the consultative expertise of Robert Rosenheck, M.D., and the Tuscaloosa VAMC vocational rehabilitation programmatic support of Thomas McNutt, Ph.D., and James Carr. The authors are grateful for the technical assistance of Catherine M. Blansett, Ph.D., Charles Li, Bonita S. Perry, M.S., Laura E. Blackburn, and Jessie McAlpine.; Dr. Davis has received a speaker honorarium and research funding from AstraZeneca. Dr. Leon served on independent data and safety monitoring boards for AstraZeneca, Sunovion, and Pfizer; served as a consultant-advisor to MedAvante and Roche; and had equity in MedAvante. The other authors report no competing interests. NR 26 TC 21 Z9 21 U1 4 U2 20 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2012 VL 63 IS 5 BP 464 EP 470 DI 10.1176/appi.ps.201100340 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 933PE UT WOS:000303373600014 PM 22307881 ER PT J AU Cassano, P Fava, M Mischoulon, D AF Cassano, Paolo Fava, Maurizio Mischoulon, David TI Major Depressive Disorder With Psychosis-like Symptoms Among Latinos SO PSYCHIATRIC SERVICES LA English DT Article ID STAR-ASTERISK-D; PSYCHIATRIC-DISORDERS; PREVALENCE; HALLUCINATIONS; AMERICAN; URBAN AB Objective: The lifetime prevalence of psychosis-like symptoms among Latinos living in the United States is 9.5%, and up to 27% of Latinos with major depressive disorder also experience psychosis-like symptoms. Yet clinicians remain Uncertain about the nature and clinical implications of these putative psychotic symptoms, and there is no consensus about treatment strategies. The authors conducted a review of the literature to examine the epidemiology, clinical features, and significance of psychosis-like symptoms among Latinos, particularly when such symptoms present with major depressive disorder, and the strategies to treat them. Methods: A search of the National Library of Medicine was conducted for all articles published through February 2011 by using the keywords "Hispanic" and "Latino" with "depression and psychotic," with "idiom of distress," and with "psychotic." Results: A total of 37 articles were reviewed. In clinical settings, the prevalence of psychosis-like symptoms among cross-sections of Latino patients ranged from 22% to 46% and was even higher among Latino veterans. Psychosis-like symptoms were associated with higher medical and psychiatric comorbidity and greater suicidality, functional impairment, and utilization of services. The authors describe the types of psychosis-like symptoms experienced by Latinos and propose criteria for the differential diagnosis of such symptoms and typical psychotic features. Conclusions: Clinicians treating depressed Latinos are often confronted with the clinical dilemma of whether to augment antidepressants with an antipsychotic. The authors argue that atypical psychotic symptoms experienced by Latinos with major depressive disorder are nonpsychotic manifestations and that antipsychotic medication should be delayed unless treatment of depression fails to address the psychosis-like symptoms. (Psychiatric Services 63:482-487, 2012; doi: 10.1176/appi.ps.201100271) C1 [Cassano, Paolo; Fava, Maurizio; Mischoulon, David] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Cassano, P (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM pcassano@partners.org RI Cassano, Paolo/I-6959-2012 FU Bowman Family Foundation; Bristol-Myers Squibb; Cederroth; FisherWallace; Ganeden; Lichtwer Pharma; Nordic Naturals FX Dr. Fawa has served as an advisor or consultant to Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes, Inc.; Amarin Pharma, Inc.; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc.; BioMarin Pharmaceuticals, Inc.; Biovail Corporation; BrainCells, Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon, Inc.; Clinical Trials Solution, LLC; CNS Response, Inc.; Compellis; Cypress Pharmaceutical, Inc.; Dainippon Sumitoma Pharma; DiagnoSearch Life Sciences (P) Ltd.; Dos' Pharmaceuticals; Edgemont Pharmaceuticals, Inc.; Eisai, Inc.; Eli Lilly; EnVivo Pharmaceuticals; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; GenOmind, LLC; GlaxoSmith Kline; Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Johnson & Johnson Pharmaceutical Research and Development, LLC; Knoll Pharmaceuticals Corporation; Labopharm, Inc.; Lorex Pharmaceuticals; Lundbeck, Inc.; MedAvante, Inc.; Merck, Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; Neuronetics, Inc.; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Otsuka Pharmaceuticals; PamLab, LLC.; Pfizer, Inc.; PharmaStar Pharmavite LLC; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc.; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC; Sepracor, Inc.; Servier Laboratories; Schering-Plough Corporation; Solvay Pharmaceuticals, Inc.; Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals, Inc.; Sunovion Pharmaceuticals; Supernus Pharmaceuticals; Synthelabo; Takeda Pharmaceutical Company, Ltd.; Tal Medical, Inc.; Tetragenex Pharmaceuticals; TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; and Vanda Pharmaceuticals, Inc. He has worked as a, speaker for or has received royalties from Adamed; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon, Inc.; CME Institute/Physicians Postgraduate Press, Inc.; Eli Lilly; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Imedex, LLC; MGH Psychiatry Acadelny/Primedia; NIGH Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals; Pfizer Inc.; PharmaStar; United BioSource Corp.; Wolters Kluwer; World Scientific Publishing; and Wyeth-Ayerst Laboratories. He has equity holdings in Compellis, holds a patent for Sequential Parallel Comparison Design and a patent for a combination of azapirones and bupropion for major depressive disorder, and collects copyright royalties for the MGH CPFQ, SFI, ATHQ, DESS, and SAFER. He holds a patent for research and licensing of SPCD with RCT Logic, Lippincott Williams & Wilkins. Dr. Mischoulon has received research support from the Bowman Family Foundation, Bristol-Myers Squibb, Cederroth, FisherWallace, Ganeden, Lichtwer Pharma and Nordic Naturals. He has received honoraria for consulting, speaking, and writing from Pamlab, Bristol-Myers Squibb, and Nordic Naturals. Hie has received royalties from Back Bay Scientific for PMS Escape and from Lippincott Williams & Wilkins. Dr. Cassano reports no competing interests. NR 24 TC 4 Z9 4 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2012 VL 63 IS 5 BP 482 EP 487 DI 10.1176/appi.ps.201100271 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 933PE UT WOS:000303373600017 PM 22422016 ER PT J AU Stoddard, F AF Stoddard, Frederick TI Post-traumatic Stress Disorder SO PSYCHIATRIC SERVICES LA English DT Book Review C1 [Stoddard, Frederick] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stoddard, F (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2012 VL 63 IS 5 BP 512 EP 513 PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 933PE UT WOS:000303373600028 ER PT J AU Forghani, R Wojtkiewicz, GR Zhang, YN Seeburg, D Bautz, BRM Pulli, B Milewski, AR Atkinson, WL Iwamoto, Y Zhang, ER Etzrodt, M Rodriguez, E Robbins, CS Swirski, FK Weissleder, R Chen, JW AF Forghani, Reza Wojtkiewicz, Gregory R. Zhang, Yinian Seeburg, Daniel Bautz, Benjamin R. M. Pulli, Benjamin Milewski, Andrew R. Atkinson, Wendy L. Iwamoto, Yoshiko Zhang, Elizabeth R. Etzrodt, Martin Rodriguez, Elisenda Robbins, Clinton S. Swirski, Filip K. Weissleder, Ralph Chen, John W. TI Demyelinating Diseases: Myeloperoxidase as an Imaging Biomarker and Therapeutic Target SO RADIOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; REMITTING MULTIPLE-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; MACROPHAGE ACTIVATION; LIPID-PEROXIDATION; INTERFERON BETA-1A; WHITE-MATTER; DOUBLE-BLIND; INFLAMMATION; MICROGLIA AB Purpose: To evaluate myeloperoxidase (MPO) as a newer therapeutic target and bis-5-hydroxytryptamide-diethylenetriaminepentaacetate-gadolinium (Gd) (MPO-Gd) as an imaging biomarker for demyelinating diseases such as multiple sclerosis (MS) by using experimental autoimmune encephalomyelitis (EAE), a murine model of MS. Materials and Methods: Animal experiments were approved by the institutional animal care committee. EAE was induced in SJL mice by using proteolipid protein (PLP), and mice were treated with either 4-aminobenzoic acid hydrazide (ABAH), 40 mg/kg injected intraperitoneally, an irreversible inhibitor of MPO, or saline as control, and followed up to day 40 after induction. In another group of SJL mice, induction was performed without PLP as shams. The mice were imaged by using MPO-Gd to track changes in MPO activity noninvasively. Imaging results were corroborated by enzymatic assays, flow cytometry, and histopathologic analyses. Significance was computed by using the t test or Mann-Whitney U test. Results: There was a 2.5-fold increase in myeloid cell infiltration in the brain (P = .026), with a concomitant increase in brain MPO level (P = .0087). Inhibiting MPO activity with ABAH resulted in decrease in MPO-Gd-positive lesion volume (P = .012), number (P = .009), and enhancement intensity (P = .03) at MR imaging, reflecting lower local MPO activity (P = .03), compared with controls. MPO inhibition was accompanied by decreased demyelination (P = .01) and lower inflammatory cell recruitment in the brain (P < .0001), suggesting a central MPO role in inflammatory demyelination. Clinically, MPO inhibition significantly reduced the severity of clinical symptoms (P = .0001) and improved survival (P = .0051) in mice with EAE. Conclusion: MPO may be a key mediator of myeloid inflammation and tissue damage in EAE. Therefore, MPO could represent a promising therapeutic target, as well as an imaging biomarker, for demyelinating diseases and potentially for other diseases in which MPO is implicated. (C) RSNA, 2012 C1 [Forghani, Reza; Wojtkiewicz, Gregory R.; Zhang, Yinian; Seeburg, Daniel; Bautz, Benjamin R. M.; Pulli, Benjamin; Milewski, Andrew R.; Atkinson, Wendy L.; Iwamoto, Yoshiko; Zhang, Elizabeth R.; Etzrodt, Martin; Rodriguez, Elisenda; Robbins, Clinton S.; Swirski, Filip K.; Weissleder, Ralph; Chen, John W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Richard B Simches Res Ctr, Boston, MA 02114 USA. [Forghani, Reza; Chen, John W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol,Dept Radiol, Boston, MA 02114 USA. [Forghani, Reza] Sir Mortimer B Davis Jewish Hosp, Montreal, PQ, Canada. [Forghani, Reza] McGill Univ, Montreal, PQ, Canada. RP Chen, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Richard B Simches Res Ctr, 185 Cambridge St,Suite 5-210, Boston, MA 02114 USA. EM jwchen@mgh.harvard.edu RI Etzrodt, Martin/P-3325-2015 OI Etzrodt, Martin/0000-0003-1928-3904 FU Dana Foundation; Department of Defense [W81WH-10-1-0694]; RSNA; Marie Curie Fellowship; Shanghai Jiao Tong University School of Medicine; National Institutes of Health [K08 HL081170, R01-NS070835, R01-NS072167]; Pfizer FX Supported in part by grants from the Dana Foundation and Department of Defense (W81WH-10-1-0694). R. F. received an RSNA Research Fellow Grant. E. R. supported by a Marie Curie Fellowship. Y.Z. supported by Shanghai Jiao Tong University School of Medicine. Address correspondence to J.W.C. (e-mail: jwchen@mgh.harvard.edu).; This research was supported by the National Institutes of Health (grants K08 HL081170, R01-NS070835, and R01-NS072167).; Financial activities related to the present article: none to disclose. Financial activities not related to the present article: owns stocks and stock options in Real Time Radiology, a teleradiology company. Other relationships: none to disclose. G. R. W. No potential conflicts of interest to disclose. Y.Z. No potential conflicts of interest to disclose. D. S. No potential conflicts of interest to disclose. B. R. M. B. No potential conflicts of interest to disclose. B. P. No potential conflicts of interest to disclose. A. R. M. No potential conflicts of interest to disclose. W. L. A. No potential conflicts of interest to disclose. Y.I. No potential conflicts of interest to disclose. E.R.Z. No potential conflicts of interest to disclose. M. E. No potential conflicts of interest to disclose. E. R. No potential conflicts of interest to disclose. C. S. R. No potential conflicts of interest to disclose. F. K. S. No potential conflicts of interest to disclose. R. W. No potential conflicts of interest to disclose. J.W.C. Financial activities related to the present article: institution received a grant from the Dana Foundation. Financial activities not related to the present article: institution received a grant from Pfizer, author receives royalties for a textbook from Elsevier. Other relationships: none to disclose. NR 48 TC 25 Z9 28 U1 1 U2 13 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 MAY PY 2012 VL 263 IS 2 BP 451 EP 460 DI 10.1148/radiol.12111593 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 929ZK UT WOS:000303104300016 PM 22438365 ER PT J AU Singh, S Kalra, MK Shenoy-Bhangle, AS Saini, A Gervais, DA Westra, SJ Thrall, JH AF Singh, Sarabjeet Kalra, Mannudeep K. Shenoy-Bhangle, Anuradha S. Saini, Aashna Gervais, Debra A. Westra, Sjirk J. Thrall, James H. TI Radiation Dose Reduction with Hybrid Iterative Reconstruction for Pediatric CT SO RADIOLOGY LA English DT Article ID TUBE CURRENT MODULATION; HELICAL CT; BODY; OPTIMIZATION; ABDOMEN; PELVIS; SIZE AB Purpose: To assess image quality and radiation dose reduction with hybrid iterative reconstruction of pediatric chest and abdominal computed tomographic (CT) data compared with conventional filtered back projection (FBP). Materials and Methods: A total of 234 patients (median age, 12 years; age range, 6 weeks to 18 years) underwent chest and abdominal CT in this institutional review board-approved HIPAA-compliant retrospective study. CT was performed with a hybrid adaptive statistical iterative reconstruction (ASIR)-enabled 64-detector row CT scanner. Scanning protocols were adjusted for clinical indication and patient weight to enable acquisition of reduced-dose CT images in all patients, and tube current was further lowered for ASIR protocols. Weight, age, and sex were recorded, and objective noise was measured in the descending thoracic aorta for chest CT and in the liver for abdominal CT. Of the 234 consecutive patients who underwent ASIR-enabled CT (115 chest and 119 abdominal examinations), 70 patients had undergone prior FBP CT. ASIR and FBP CT studies (29 chest and 41 abdominal studies) in these 70 patients were reviewed for image quality, artifacts, and diagnostic confidence by two pediatric radiologists working independently. Data were analyzed with multiple paired t tests. Results: Compared with FBP, ASIR enabled dose reduction of 46.4% (3.7 vs 6.9 mGy) for chest CT and 38.2% (5.0 vs 8.1 mGy) for abdominal CT (P < .0001). Both radiologists deemed image quality of and diagnostic confidence with ASIR and FBP CT images as acceptable, without any artifacts. Despite the lower radiation dose used, ASIR images (chest, 10.7 +/- 2.5 [mean 6 standard deviation]; abdomen, 11.8 +/- 3.4) had substantially less objective noise than did FBP images (chest, 13.3 +/- 3.8; abdomen, 13.8 +/- 5.2) (P = .001, P =. 006, respectively). Conclusion: Use of a hybrid iterative reconstruction technique, such as ASIR, enables substantial radiation dose reduction for pediatric CT when compared with FBP and maintains image quality and diagnostic confidence. (C) RSNA, 2012 C1 [Singh, Sarabjeet; Kalra, Mannudeep K.; Shenoy-Bhangle, Anuradha S.; Saini, Aashna; Gervais, Debra A.; Westra, Sjirk J.; Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Singh, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,4th Floor, Boston, MA 02114 USA. EM ssingh@partners.org FU GE Healthcare FX S.S. No potential conflicts of interest to disclose. M. K. K. Financial activities related to the present article: institution received a research grant from GE Healthcare. Financial activities not related to the present article: received an honorarium for continued education talks from GE Healthcare. Other relationships: none to disclose. A. S. S. No potential conflicts of interest to disclose. A. S. No potential conflicts of interest to disclose. D. A. G. No potential conflicts of interest to disclose. S.J.W. No potential conflicts of interest to disclose. J.H.T. No potential conflicts of interest to disclose. NR 19 TC 64 Z9 66 U1 1 U2 5 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 MAY PY 2012 VL 263 IS 2 BP 537 EP 546 DI 10.1148/radiol.12110268 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 929ZK UT WOS:000303104300026 PM 22517962 ER PT J AU Boland, GWL AF Boland, Giles W. L. TI Incidental Adrenal Lesions Response SO RADIOLOGY LA English DT Letter C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2012 VL 263 IS 2 BP 619 EP 620 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 929ZK UT WOS:000303104300039 ER PT J AU Werner, MU Bischoff, JM Rathmell, JP Kehlet, H AF Werner, Mads U. Bischoff, Joakim M. Rathmell, James P. Kehlet, Henrik TI Pulsed Radiofrequency in the Treatment of Persistent Pain After Inguinal Herniotomy A Systematic Review SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article ID LOCAL-ANESTHETIC BLOCKADE; PLACEBO; RECOMMENDATIONS; HERNIORRHAPHY; NEURALGIAS AB In the United States, it is estimated that between 6000 and 18,000 individuals each year present with disabling pain after inguinal hernia repair. Although surgical treatment with mesh removal is one of few options available, effective alternatives to nonsurgical management are needed. The use of pulsed radiofrequency (PFR), leading to nondestructive lesions of nerve structures, has been proposed as a treatment option. To examine the evidence of treatment efficacy, a systematic literature search was made. From the databases PubMed, Embase, and CINAHL, 4 case reports were retrieved and 8 patients were included for analysis. The PFR treatment was peripheral (n = 4) and central (n = 4). Pain relief varied between 63% and 100%, the follow-up period was 3 to 9 months, and no adverse effects or complications were reported. In conclusion, the evidence base of PRF in persistent pain after inguinal herniotomy is fairly limited. Suggestions for improved research strategies are presented. C1 [Werner, Mads U.] Univ Copenhagen, Rigshosp, Ctr Multidisciplinary Pain, DK-2100 Copenhagen O, Denmark. [Bischoff, Joakim M.; Kehlet, Henrik] Univ Copenhagen, Rigshosp, Sect Surg Pathophysiol, DK-1168 Copenhagen, Denmark. [Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Werner, MU (reprint author), Univ Copenhagen, Rigshosp, Ctr Multidisciplinary Pain, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark. EM mads.u.werner@gmail.com FU Europain project; Innovative Medicines Initiative Joint Undertaking [115007] FX Supported by a grant from the Europain project, which is funded by the Innovative Medicines Initiative Joint Undertaking (grant no. 115007). NR 27 TC 11 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1098-7339 EI 1532-8651 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD MAY-JUN PY 2012 VL 37 IS 3 BP 340 EP 343 DI 10.1097/AAP.0b013e31824bea4e PG 4 WC Anesthesiology SC Anesthesiology GA 933VH UT WOS:000303391500018 PM 22476237 ER PT J AU Lerman, IR Souzdalnitski, D Narouze, S AF Lerman, Imanuel R. Souzdalnitski, Dmitri Narouze, Samer TI A Low-Cost, Durable, Combined Ultrasound and Fluoroscopic Phantom for Cervical Transforaminal Injections SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article ID INTERVERTEBRAL FORAMINA; LEARNING-CURVE; ANESTHESIA; RESIDENTS; ARTERY; SPINE AB Background: This technical report describes a durable, low-cost, anatomically accurate, and easy-to-prepare combined ultrasound (US) and fluoroscopic phantom of the cervical spine. This phantom is meant to augment training in US-and fluoroscopic-guided pain medicine procedures. Methods: The combined US and fluoroscopic phantom (CUF-P) is prepared from commercially available liquid plastic that is ordinarily used to prepare synthetic fishing lures. The liquid plastic is heated and then poured into a metal canister that houses an anatomical cervical spine model. Drops of dark purple dye are added to make the phantom opaque. After cooling, tubing is attached to the CUF-P to simulate blood vessels. Results: The CUF-P accurately simulates human tissue by imitating both the tactile texture of skin and the haptic resistance of human tissue as the needle is advanced. This phantom contains simulated fluid-filled vertebral arteries that exhibit pulsed flow under color Doppler US. Under fluoroscopic examination, the CUF-P-simulated vertebral arteries also exhibit uptake of contrast dye if mistakenly injected. Conclusions: The creation of a training phantom allows the pain physician to practice needle positioning technique while simultaneously visualizing both targeted and avoidable vascular structures under US and fluoroscopic guidance. This low-cost CUF-P is easy to prepare and is reusable, making it an attractive alternative to current homemade and commercially available phantom simulators. C1 [Lerman, Imanuel R.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Souzdalnitski, Dmitri] Cleveland Clin Fdn, Inst Anesthesiol, Dept Pain Med, Cleveland, OH 44195 USA. [Narouze, Samer] Summa Western Reserve Hosp, Ctr Pain Med, Cuyahoga Falls, OH USA. RP Lerman, IR (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM irlerman@partners.org FU Yale New Haven Hospital FX This study was supported by the Yale New Haven Hospital Resident Education Fund. NR 24 TC 8 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD MAY-JUN PY 2012 VL 37 IS 3 BP 344 EP 348 DI 10.1097/AAP.0b013e31824f3763 PG 5 WC Anesthesiology SC Anesthesiology GA 933VH UT WOS:000303391500019 PM 22476241 ER PT J AU Whitford, TJ Ford, JM Mathalon, DH Kubicki, M Shenton, ME AF Whitford, Thomas J. Ford, Judith M. Mathalon, Daniel H. Kubicki, Marek Shenton, Martha E. TI Schizophrenia, Myelination, and Delayed Corollary Discharges: A Hypothesis SO SCHIZOPHRENIA BULLETIN LA English DT Article DE white matter; dopamine; neurodevelopment; salience; self-monitoring; efference copy; myelin ID WHITE-MATTER ABNORMALITIES; RECENT-ONSET SCHIZOPHRENIA; MULTIPLE-SCLEROSIS; SYNAPTIC PLASTICITY; AUDITORY HALLUCINATIONS; PSYCHIATRIC-DISORDERS; NERVOUS-SYSTEM; OPTIC NEURITIS; D-2 RECEPTORS; PSYCHOSIS AB Any etiological theory of schizophrenia must account for at least 3 distinctive features of the disorder, namely its excessive dopamine neurotransmission, its frequent periadolescent onset, and its bizarre, pathognomonic symptoms. In this article, we theorize that each of these features could arise from a single underlying cause-namely abnormal myelination of late-developing frontal white matter fasciculi. Specifically, we suggest that abnormalities in frontal myelination result in conduction delays in the efference copies initiated by willed actions. These conduction delays cause the resulting corollary discharges to be generated too late to suppress the sensory consequences of the willed actions. The resulting ambiguity as to the origins of these actions represents a phenomenologically and neurophysiologically significant prediction error. On a phenomenological level, the perception of salience in a self-generated action leads to confusion as to its origins and, consequently, passivity experiences and auditory hallucinations. On a neurophysiological level, this prediction error leads to the increased activity of dopaminergic neurons in the midbrain. This dopaminergic activity causes previously insignificant events to be perceived as salient, which exacerbates the budding hallucinations and passivity experiences and triggers additional first-rank symptoms such as delusions of reference. The article concludes with a discussion of the implications of the theory and some testable predictions which may form a worthwhile basis for future research. C1 [Whitford, Thomas J.; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02215 USA. [Whitford, Thomas J.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Dept Psychiat, Melbourne, Vic, Australia. [Whitford, Thomas J.] Melbourne Hlth, Melbourne, Vic, Australia. [Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Ford, Judith M.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Boston Vet Affairs Healthcare Syst, Clin Neurosci Div, Lab Neurosci,Dept Psychiat,Med Sch, Brockton, MA 02401 USA. RP Whitford, TJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, 1249 Boylston St, Boston, MA 02215 USA. EM whitford@bwh.harvard.edu OI Mathalon, Daniel/0000-0001-6090-4974 FU National Health and Medical Research Council of Australia [NHMRC 520627]; National Institutes of Health [R01 MH076989, R01 MH058262, K02 MH067967, R03 MH068464-0, R01 MH 50747, K05 MH 070047, P50 MH 080272]; Harvard Medical School; Department of Veterans Affairs; Department of Veterans Affairs (VA Schizophrenia Research Center) FX National Health and Medical Research Council of Australia (NHMRC 520627 to T.J.W.); the National Institutes of Health (R01 MH076989 to D. H. M.; R01 MH058262 and K02 MH067967 to J.M.F.; R03 MH068464-0 to M. K.; R01 MH 50747, K05 MH 070047, and P50 MH 080272 to M. E. S.); Harvard Medical School (Milton Award); Department of Veterans Affairs (VA Merit Review to J.M.F., VA Merit Award, VA Research Enhancement Award Program, and VA Schizophrenia Research Center Grant to M.E.S.). NR 91 TC 45 Z9 45 U1 2 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2012 VL 38 IS 3 BP 486 EP 494 DI 10.1093/schbul/sbq105 PG 9 WC Psychiatry SC Psychiatry GA 930VB UT WOS:000303169000016 PM 20855415 ER PT J AU Guan, X Yabuuchi, A Huo, HG Ginsberg, E Racowsky, C Daley, GQ Lerou, PH AF Guan, Xiao Yabuuchi, Akiko Huo, Hongguang Ginsberg, Elizabeth Racowsky, Catherine Daley, George Q. Lerou, Paul H. TI Derivation of human embryonic stem cells with NEMO deficiency SO STEM CELL RESEARCH LA English DT Article ID NF-KAPPA-B; ANHIDROTIC ECTODERMAL DYSPLASIA; X-INACTIVATION; MUTATIONS; LINES; DISORDERS AB Deficiency of the nuclear factor-kappa-B essential modulator (NEMO) is a rare X-linked disorder that presents in boys as hypohydrotic ectodermal dysplasia with immunodeficiency due to defective nuclear factor-kappa B activation. Here we report on the generation of 2 human embryonic stem cell lines from discarded in vitro fertilization (IVF) embryos ascertained via preimplantation genetic diagnosis. We have derived two human embryonic stem cell lines that carry a T458G hypomorphic mutation in exon 4 of the NEMO (or IKBKG) gene. One of the lines is diploid male; the other is diploid female but has clonally inactivated the X-chromosome that harbors the wild-type IKBKG gene. We show that both lines are pluripotent, have the capacity to differentiate into hematopoietic progenitors, and have defective inhibitor of nuclear factor kappa-B kinase activity. These NEMO deficiency hES cell lines provide an unlimited source for differentiated cell types and may serve as a unique tool to study NEMO deficiency and potentially lead to the development of new therapies for this disease. (C) 2011 Elsevier B.V. All rights reserved. C1 [Guan, Xiao; Lerou, Paul H.] Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. [Guan, Xiao; Lerou, Paul H.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Guan, Xiao; Lerou, Paul H.] Childrens Hosp, Dept Med, Div Newborn Med, Boston, MA 02115 USA. [Guan, Xiao; Yabuuchi, Akiko; Huo, Hongguang; Daley, George Q.; Lerou, Paul H.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Yabuuchi, Akiko; Huo, Hongguang; Daley, George Q.] Childrens Hosp Boston, Dana Farber Canc Inst, Dept Med, Div Pediat Hematol Oncol, Boston, MA USA. [Ginsberg, Elizabeth; Racowsky, Catherine] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. [Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA USA. RP Daley, GQ (reprint author), Karp Family Res Labs, Room 7214,1 Blackfan Circle, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu; plerou@partners.org RI Guan, Xiao/D-5656-2013 FU Foundation for Anemia Research, Alex's Lemonade Stand; Harvard Stem Cell Institute; Burroughs Wellcome Fund; Leukemia and Lymphoma Society; Howard Hughes Medical Institute; Charles H. Hood Foundation FX This study was supported by the Foundation for Anemia Research, Alex's Lemonade Stand, the Harvard Stem Cell Institute, the Burroughs Wellcome Fund, the Leukemia and Lymphoma Society, and the Howard Hughes Medical Institute (to G.Q.D.). This is also supported by a grant from the Harvard Stem Cell Institute and Charles H. Hood Foundation (to P.H.L.). NR 28 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 J9 STEM CELL RES JI Stem Cell Res. PD MAY PY 2012 VL 8 IS 3 BP 410 EP 415 DI 10.1016/j.scr.2011.12.007 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 932QJ UT WOS:000303305300008 PM 22284529 ER PT J AU Revicki, DA Camilleri, M Kuo, B Szarka, LA Mccormack, J Parkman, HP AF Revicki, D. A. Camilleri, M. Kuo, B. Szarka, L. A. Mccormack, J. Parkman, H. P. TI Evaluating symptom outcomes in gastroparesis clinical trials: validity and responsiveness of the Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE clinical endpoints; clinical significance; daily diary; gastroparesis; Gastroparesis Cardinal Symptom Scale; patient-reported outcome; responsiveness; validity ID UPPER GASTROINTESTINAL DISORDERS; GASTRIC-EMPTYING SCINTIGRAPHY; FUNCTIONAL DYSPEPSIA; DIABETIC GASTROPARESIS; BOTULINUM-TOXIN; HEALTH-STATUS; SEVERITY; STIMULATION; ASSOCIATION; VALIDATION AB Background Patient-reported symptom scales are needed to evaluate treatments for gastroparesis. The Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) was developed to assess daily symptoms of gastroparesis. This study evaluated the validity and responsiveness of the GCSI-DD in patients with gastroparesis. Methods Symptomatic patients were started with a new treatment for gastroparesis. Patients completed the GCSI-DD each evening during a baseline week and for 8 weeks of treatment. Responders were defined based on patient and clinician global rating of change. Minimal important differences (MID) were estimated based on baseline to 4 week changes in symptoms scores for small improvements. Key Results Of 69 patients participating, 46 had idiopathic, 19 diabetic, and four postfundoplication gastroparesis. Excellent test-retest reliability was seen for GCSI-DD scores, and there were significant correlations between GCSI-DD scores and clinician ratings of symptom severity. Responders to treatment reported improvements in nausea [effect size (ES) = 0.42, P < 0.001], postprandial fullness, ES = 0.83, P < 0.001), bloating (ES = 0.34, P < 0.001), early satiety (ES = 0.53, P < 0.001), but lower responses for upper abdominal pain (ES = 0.29), and vomiting (ES = 0.22; P = 0.119). MIDs were 0.55 for nausea, 0.97 for excessive fullness, 0.63 for bloating, 0.77 for postprandial fullness, and 0.30 for abdominal pain. A composite score of four symptoms (Composite-1; nausea, bloating, excessive fullness, postprandial fullness) had ES of 0.61 and MID of 0.73. Composite-2 score (nausea, early satiety, bloating, abdominal pain) had a lower ES of 0.47. Conclusions & Inferences Symptoms of early satiety, nausea, postprandial fullness, and bloating were responsive to treatment for gastroparesis. A composite of these symptoms also demonstrates validity and responsiveness to treatment for gastroparesis, and may represent an acceptable endpoint for evaluating the effectiveness of medical treatments in clinical trials for gastroparesis. C1 [Revicki, D. A.; Mccormack, J.] United BioSource Corp, Bethesda, MD 20814 USA. [Camilleri, M.; Szarka, L. A.] Mayo Clin, Rochester, MN USA. [Kuo, B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Parkman, H. P.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. RP Revicki, DA (reprint author), United BioSource Corp, 7101 Wisconsin Ave,Suite 600, Bethesda, MD 20814 USA. EM dennis.revicki@unitedbiosource.com FU American Neurogastroenterology; Motility Society FX This research was supported by the American Neurogastroenterology and Motility Society. NR 40 TC 27 Z9 27 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAY PY 2012 VL 24 IS 5 BP 456 EP + DI 10.1111/j.1365-2982.2012.01879.x PG 10 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 923IH UT WOS:000302612500012 PM 22284754 ER PT J AU Hope, MD Urbania, TH Yu, JPJ Chitsaz, S Tseng, E AF Hope, Michael D. Urbania, Thomas H. Yu, John-Paul J. Chitsaz, Sam Tseng, Elaine TI Incidental Aortic Valve Calcification on CT Scans: Significance for Bicuspid and Tricuspid Valve Disease SO ACADEMIC RADIOLOGY LA English DT Article DE Bicuspid aortic valve; aortic stenosis; aortic valve calcification ID CLINICAL-SIGNIFICANCE; STENOSIS; PROGRESSION; TOMOGRAPHY; PREVALENCE; AGE AB Rationale and Objectives: The aim of this study was to evaluate the role of incidental aortic valve calcification on routine computed tomographic scans as a marker for stenosis, as assessed by echocardiography, in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve. Materials and Methods: Computed tomographic and echocardiographic studies were retrospectively reviewed for 182 consecutive, unselected patients and 426 patients identified by a record search for "aortic valve calcification." Location and severity of valve calcification were correlated with aortic valve morphology and stenosis. Differences between subgroups were assessed using chi(2) or Fisher's exact tests. Results: In unselected patients, calcification was present in 25.8% with tricuspid aortic valves (46 of 178) and 75% (three of four) with BAV. In patients selected for valve calcification, the average age of those with tricuspid aortic valves (n = 395) was 14.3 years older than those with BAV (n = 31). Patients with BAV were more likely to have severe calcification (87% vs 50%, P <.001), and if severe, calcification was present, it was more likely to involve only the valve leaflets (41% vs 9%, P < .001) and result in aortic stenosis (85% vs 58%, P = .006). Patients aged < 60 years with severe calcification were more likely to have BAV (56% vs 7%; odds ratio, 7.9; 95% confidence interval, 3.4-18.7). Conclusions: Aortic valve calcification was found 14 years earlier in patients with BAV and was more severe and strongly linked to aortic stenosis. Valve calcification on computed tomographic scans should be considered a marker for BAV if found before the seventh decade. C1 [Hope, Michael D.; Urbania, Thomas H.; Yu, John-Paul J.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Chitsaz, Sam; Tseng, Elaine] San Francisco VA Med Ctr, Dept Cardiothorac Surg, San Francisco, CA USA. RP Hope, MD (reprint author), Univ Calif San Francisco, Dept Radiol, 505 Parnassus Ave,Box 0628, San Francisco, CA 94143 USA. EM michael.hope@ucsf.edu RI Chitsaz, Sam/C-4586-2008; OI Yu, John-Paul/0000-0003-1878-052X NR 14 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 2012 VL 19 IS 5 BP 542 EP 547 DI 10.1016/j.acra.2011.10.012 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 929OR UT WOS:000303075700006 PM 22104287 ER PT J AU Kuter, DJ Mathias, SD Rummel, M Mandanas, R Giagounidis, AA Wang, XN Deuson, RR AF Kuter, David J. Mathias, Susan D. Rummel, Mathias Mandanas, Romeo Giagounidis, Aristoteles A. Wang, Xuena Deuson, Robert R. TI Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID DISEASE-SPECIFIC MEASURE; CHRONIC ITP; PURPURA; ADULTS; EFFICACY; TRIALS C1 [Kuter, David J.] Massachusetts Gen Hosp, Dept Hematol, Boston, MA 02114 USA. [Mathias, Susan D.] Hlth Outcomes Solut, Patient Reported Outcomes Res Dept, Winter Pk, FL USA. [Rummel, Mathias] Klinikum Justus Liebig Univ, Dept Hematol, Glessen, Germany. [Mandanas, Romeo] Integris Canc Inst Oklahoma, Dept Hematol Oncol, Oklahoma City, OK USA. [Giagounidis, Aristoteles A.] St Johannes Hosp, Dept Hematol, Duisburg, Germany. [Wang, Xuena] Amgen Inc, Dept Global Biostat Sci, Thousand Oaks, CA 91320 USA. [Deuson, Robert R.] Amgen Inc, Dept Global Hlth Econ, Thousand Oaks, CA 91320 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Dept Hematol, Boston, MA 02114 USA. EM kuter.david@MGH.harvard.edu NR 18 TC 23 Z9 24 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 IS 5 BP 558 EP 561 DI 10.1002/ajh.23163 PG 4 WC Hematology SC Hematology GA 927IC UT WOS:000302899900027 PM 22460421 ER PT J AU Jotwani, V Li, YM Grunfeld, C Choi, AI Shlipak, MG AF Jotwani, Vasantha Li, Yongmei Grunfeld, Carl Choi, Andy I. Shlipak, Michael G. TI Risk Factors for ESRD in HIV-Infected Individuals: Traditional and HIV-Related Factors SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE End-stage renal disease; human immunodeficiency virus (HIV); chronic kidney disease; risk factors ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; ACTIVE ANTIRETROVIRAL THERAPY; OF-VETERANS-AFFAIRS; CARDIOVASCULAR EVENTS; CYSTATIN C; COHORT; ASSOCIATION; PREVALENCE; NEPHROPATHY AB Background: Despite improvements in survival with human immunodeficiency virus (HIV) infection, kidney disease remains an important complication. Few studies have evaluated risk factors associated with the development of end-stage renal disease (ESRD) in HIV-infected individuals. We sought to identify traditional and HIV-related risk factors for ESRD in HIV-infected individuals and compare ESRD risk by estimated glomerular filtration rate (eGFR) and proteinuria levels. Study Design: Retrospective cohort study. Setting & Participants: 22,156 HIV-infected veterans without pre-existing ESRD receiving health care in the Veterans' Affairs medical system between 1996 and 2004. Predictors: Hypertension, diabetes, cardiovascular disease, hypoalbuminemia (serum albumin <3.5 mg/dL), CD4 lymphocyte count, HIV viral load, hepatitis C virus coinfection, proteinuria, and eGFR were identified using the Veterans' Affairs electronic record system. Outcomes: ESRD was ascertained by the US Renal Data System. Results: 366 cases of ESRD occurred, corresponding to 3 cases/1,000 person-years. Hypertension (HR, 1.9; 95% CI, 1.5-2.4), diabetes (HR, 1.7; 95% CI, 1.3-2.2), and cardiovascular disease (HR, 2.2; 95% CI, 1.7-2.7) were associated independently with ESRD risk in multivariate-adjusted models, as were CD4 lymphocyte count <200 cells/mu L (HR, 1.5; 95% CI, 1.2-2.0), HIV viral load >= 30,000 copies/mL (HR, 2.0; 95% CI, 1.5-2.8), hepatitis C virus coinfection (HR, 1.9; 95% CI, 1.5-2.4), and hypoalbuminemia (HR, 2.1; 95% CI, 1.8-2.5). Compared with persons without chronic kidney disease, defined as eGFR >60 mL/min/1.73 m(2) and no proteinuria, lower eGFR and higher proteinuria categories were associated jointly with exponentially higher ESRD rates, ranging from 6.6 events/1,000 person-years for persons with urine protein excretion of 30-100 mg/dL and eGFR >60 mL/min/1.73 m(2) to 193 events/1,000 person-years for persons with urine protein excretion >= 300 mg/dL and eGFR <30 mL/min/1.73 m(2). Limitations: Results may not be generalizable to female and nonveteran populations. Conclusions: In HIV-infected persons, ESRD risk appears attributable to a combination of traditional and HIV-related risk factors for kidney disease. Combining eGFR and proteinuria for chronic kidney disease staging is most effective for stratifying the risk of ESRD. Am J Kidney Dis. 59(5): 628-635. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Shlipak, Michael G.] Univ Calif San Francisco, Gen Internal Med Sect, Vet Affairs Med Ctr 111A1, Div Gen Internal Med, San Francisco, CA 94121 USA. [Jotwani, Vasantha; Li, Yongmei; Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. [Grunfeld, Carl] San Francisco VA Med Ctr, Div Endocrinol, San Francisco, CA USA. [Choi, Andy I.] San Francisco VA Med Ctr, Div Nephrol, San Francisco, CA USA. RP Shlipak, MG (reprint author), Univ Calif San Francisco, Gen Internal Med Sect, Vet Affairs Med Ctr 111A1, Div Gen Internal Med, 4150 Clement St, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU National Institutes of Health [K23DK080645-01A1, 1R03AG034871-01, R01 DK066488-01] FX This study was supported by National Institutes of Health grants K23DK080645-01A1 (A.I.C.), 1R03AG034871-01 (A.I.C.), R01 DK066488-01 (M.G.S.), which were administered by the Northern California Institute for Research and Education, and with resources of the VA Medical Center, San Francisco, CA. These funding sources had no involvement in the design or execution of this study. NR 44 TC 48 Z9 50 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2012 VL 59 IS 5 BP 628 EP 635 DI 10.1053/j.ajkd.2011.10.050 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 926XH UT WOS:000302864700009 PM 22206742 ER PT J AU Lee, CH Marino-Enriquez, A Ou, WB Zhu, MJ Ali, RH Chiang, S Amant, F Gilks, CB van de Rijn, M Oliva, E Debiec-Rychter, M Dal Cin, P Fletcher, JA Nucci, MR AF Lee, Cheng-Han Marino-Enriquez, Adrian Ou, Wenbin Zhu, Meijun Ali, Rola H. Chiang, Sarah Amant, Frederic Gilks, C. Blake van de Rijn, Matt Oliva, Esther Debiec-Rychter, Maria Dal Cin, Paola Fletcher, Jonathan A. Nucci, Marisa R. TI The Clinicopathologic Features of YWHAE-FAM22 Endometrial Stromal Sarcomas: A Histologically High-grade and Clinically Aggressive Tumor SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT USCAP Annual Meeting CY 2011 CL San Antonio, TX SP USCAP DE endometrial stromal sarcoma; 14-3-3; YWHAE; FAM22; JAZF1 ID JAZF1-JJAZ1 GENE FUSION; CLEAR-CELL-SARCOMA; SMOOTH-MUSCLE DIFFERENTIATION; RECURRING TRANSLOCATION; MOLECULAR ANALYSIS; PROGNOSTIC-FACTORS; UTERINE SARCOMAS; NEOPLASMS; KIDNEY; HETEROGENEITY AB Endometrial stromal sarcoma (ESS) is a genetically heterogenous group of uterine sarcomas, of which almost half are associated with JAZF1 rearrangement. We recently identified a novel genetic fusion between YWHAE and FAM22A/B in ESS harboring t(10; 17)(q22; p13) and herein describe the clinicopathologic features of 13 YWHAE-FAM22 ESS cases (11 primary and 3 metastatic) and compare them with 20 ESS cases with JAZF1 rearrangement. Ten of 11 primary uterine tumors contained morphologically high-grade areas composed of round cells arranged in nests with a delicate stromal capillary network. The tumor cells showed large nuclei with irregular nuclear contours and significant mitotic activity (> 10 mitoses/10 HPF) in addition to focal tumor necrosis, in contrast to JAZF1 ESS, which lacked a nested growth pattern, were composed of cells with small round/oval nuclei, and typically had < 5 MF/10 HPF. In 7 of the 11 uterine tumors, there was an additional cytologically bland and mitotically weakly active spindle cell component with a fibrous/fibromyxoid stroma (ESS, fibromyxoid variant). Two metastatic tumors (pulmonary) also contained round cell and spindle cell components, whereas 1 metastasis (vaginal) was composed solely of the spindle cell component. In both primary and metastatic tumors, the spindle cells were diffusely positive for estrogen and progesterone receptors and CD10, in contrast to the round cell areas, which were negative. Clinically, 10 of 12 patients with YWHAE-FAM22 ESS presented with FIGO stages II to III disease, in contrast to only 4 of 16 patients with JAZF1 ESS presenting with stages II to III disease (P < 0.05). Tumors with YWHAE-FAM22 rearrangements constitute a distinct group of ESS, which is associated with high-grade morphology and aggressive clinical behavior compared to JAZF1 ESS. Thus, their distinction from typical JAZF1 ESS is important for prognostic and therapeutic purposes. C1 [Lee, Cheng-Han; Marino-Enriquez, Adrian; Ou, Wenbin; Zhu, Meijun; Dal Cin, Paola; Fletcher, Jonathan A.; Nucci, Marisa R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chiang, Sarah; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lee, Cheng-Han; Ali, Rola H.; Gilks, C. Blake] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. [Amant, Frederic] Catholic Univ Louvain, Dept Oncol, B-3000 Louvain, Belgium. [Debiec-Rychter, Maria] Catholic Univ Louvain, Dept Human Genet, B-3000 Louvain, Belgium. Univ Hosp, Louvain, Belgium. [van de Rijn, Matt] Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA. RP Nucci, MR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3, Boston, MA 02115 USA. EM mnucci@partners.org OI Ali, Rola/0000-0001-5747-8900 NR 41 TC 64 Z9 66 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 2012 VL 36 IS 5 BP 641 EP 653 DI 10.1097/PAS.0b013e31824a7b1a PG 13 WC Pathology; Surgery SC Pathology; Surgery GA 926EL UT WOS:000302814000001 PM 22456610 ER PT J AU Kelly, PJ Shinagare, S Sainani, N Hong, X Ferrone, C Yilmaz, O Fernandez-del Castillo, C Lauwers, GY Deshpande, V AF Kelly, Paul J. Shinagare, Shweta Sainani, Nisha Hong, Xiao Ferrone, Cristina Yilmaz, Omer Fernandez-del Castillo, Carlos Lauwers, Gregory Y. Deshpande, Vikram TI Cystic Papillary Pattern in Pancreatic Ductal Adenocarcinoma: A Heretofore Undescribed Morphologic Pattern That Mimics Intraductal Papillary Mucinous Carcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE pancreatic ductal adenocarcinoma; intraductal papillary mucinous neoplasm; cystic papillary pattern ID NEOPLASMS; EXPRESSION; DISTINCT AB Introduction: The prototypic pancreatic ductal adenocarcinoma shows small-caliber glands that are placed within an exuberant desmoplastic stromal reaction. A number of histologic patterns have been described, and the majority of these patterns are genetically and biologically related to conventional ductal adenocarcinomas. In this report we describe our experience with a heretofore undescribed histologic pattern of pancreatic adenocarcinoma that mimics intraductal papillary mucinous carcinoma, both morphologically and radiologically. Methods: We identified 10 cases of pancreatic adenocarcinoma with large-caliber malignant glands and an intraluminal papillary pattern. The demographic, clinical, radiologic, and outcome data were recorded. In addition to a review of the histologic features we also performed elastin stains, immunohistochemistry for selected oncogenes and tumor suppressor genes including SMAD4. Immunohistochemical staining for MUC proteins was also performed. Results: The median age of the patients was 67 years, and there were 6 women and 4 men. Grossly, the cut surface in 6 of these cases showed an admixture of solid and cystic areas. The papillary cystic architecture was intimately mixed with areas of conventional adenocarcinoma, the latter characterized by invasive small-caliber tubular structures. None of the tumors showed a pure papillary cystic pattern; however, in 8 cases, this was the predominant pattern (> 50% of the tumor). The cysts and papillae were lined predominantly by tall columnar hypermucinous epithelium. Elastin fibers were not identified around these dilated malignant cysts and glands. The intratumoral stroma was paucicellular and hyalinized. Seven of the 10 tumors were negative for SMAD4. The lack of pericystic elastin fibers and loss of SMAD4 in the majority of cases argue against these lesions representing an intraductal papillary mucinous neoplasm. All 10 tumors stained for MUC1; focal MUC2 reactivity was noted in 1 case. The majority of cases were positive for MUC5AC (9/10) and MUC6 (8/10). Seven patients died of their disease, whereas 1 patient is alive with widely metastatic disease. Two patients were lost to follow up. Conclusions: The adenocarcinoma described herein is a unique morphologic pattern of pancreatic ductal adenocarcinoma. The biology and genetics (as estimated by immunohistochemistry) are no different from that of conventional ductal adenocarcinoma but are distinctly different from that of an intraductal papillary mucinous carcinoma, its closest morphologic mimic. C1 [Shinagare, Shweta; Hong, Xiao; Yilmaz, Omer; Lauwers, Gregory Y.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sainani, Nisha] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ferrone, Cristina; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kelly, Paul J.] Royal Victoria Hosp, Dept Pathol, Belfast, Antrim, North Ireland. Harvard Univ, Sch Med, Boston, MA USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 2, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 14 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 2012 VL 36 IS 5 BP 696 EP 701 DI 10.1097/PAS.0b013e318249ce1c PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 926EL UT WOS:000302814000006 PM 22367300 ER PT J AU Eberle, FC Song, JY Xi, LQ Raffeld, M Harris, NL Wilson, WH Pittaluga, S Jaffe, ES AF Eberle, Franziska C. Song, Joo Y. Xi, Liqiang Raffeld, Mark Harris, Nancy Lee Wilson, Wyndham H. Pittaluga, Stefania Jaffe, Elaine S. TI Nodal Involvement by Cutaneous CD30-positive T-cell Lymphoma Mimicking Classical Hodgkin Lymphoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE CD30-positive T-cell lymphoma; classical Hodgkin lymphoma; lymphomatoid papulosis; mycosis fungoides; transformation; primary cutaneous CD30-positive T-cell lymphoproliferative; disorder ID REED-STERNBERG CELLS; MYCOSIS-FUNGOIDES; GENE REARRANGEMENTS; MOLECULAR EVIDENCE; ACTIVATOR PROTEIN; DISEASE; PAPULOSIS; EXPRESSION; FEATURES; ORIGIN AB An association between classical Hodgkin lymphoma (cHL) and mycosis fungoides (MF) or lymphomatoid papulosis has been reported in the literature. However, there can be considerable morphologic and immunophenotypic overlap between cHL and nodal involvement by CD30-positive T-cell lymphoproliferative disorders (CD30-T-LPD). To examine this potential association, biopsies from patients with a history of MF or primary cutaneous CD30-T-LPD and lymph node biopsies reported as either CD30-positive T-cell lymphoma (TCL) with Hodgkin-like cells or cHL were retrieved from the authors' institution. Of 11 cases identified, 10 were considered CD30-positive TCL with Hodgkin-like cells, whereas 1 was confirmed as cHL upon review. Five cases originally diagnosed as cHL were revised as CD30-positive TCL. Cases of CD30-positive TCL with Hodgkin-like cells showed a male predominance (M:F, 4:1) with a median age of 53 years (range, 44 to 72 y). Nearly all patients (9/10) initially presented with skin lesions. In 7/10 patients the draining lymph node was involved, whereas in 3 cases this could not be confirmed. Tumor cells morphologically resembled Hodgkin/Reed-Sternberg cells; they were uniformly strongly positive for CD30, and CD15 was expressed in 9/10 (90%) cases. A T-cell derivation was confirmed by T-cell antigen expression (7/10) and clonal rearrangement of T-cell receptor genes (9/10). In 3 cases a common T-cell clone was identified in skin and lymph node. B-cell markers (CD20/PAX5) were consistently negative. In 1 case the diagnosis of cHL followed by lymphomatoid papulosis was confirmed, with Hodgkin/Reed-Sternberg cells expressing PAX5, CD30, and CD15. In situ hybridization studies for Epstein Barr virus were negative. We show that cHL is less often associated with MF and primary cutaneous CD30-T-LPD than previously thought and that the coexpression of CD30 and CD15 in these TCLs may lead to a mistaken diagnosis of cHL. C1 [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Wilson, Wyndham H.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. EM ejaffe@mail.nih.gov RI Song, Joo/E-5356-2016; OI Song, Joo/0000-0003-3497-2513; Jaffe, Elaine/0000-0003-4632-0301 FU Center for Cancer Research, National Cancer Institute, NIH FX Supported by funding from the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 28 TC 16 Z9 16 U1 0 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 MAY PY 2012 VL 36 IS 5 BP 716 EP 725 DI 10.1097/PAS.0b013e3182487158 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 926EL UT WOS:000302814000009 PM 22367293 ER PT J AU Alvarez, T Miller, E Duska, L Oliva, E AF Alvarez, Teresa Miller, Ezra Duska, Linda Oliva, Esther TI Molecular Profile of Grade 3 Endometrioid Endometrial Carcinoma: Is it a Type I or Type II Endometrial Carcinoma? SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometrial endometrioid carcinoma; grade 3; immunohistochemistry; molecular profile ID DNA MISMATCH REPAIR; SEROUS PAPILLARY CARCINOMA; TUMOR GENE WT1; MICROSATELLITE INSTABILITY; CYCLIN D1; CLEAR-CELL; IMMUNOHISTOCHEMICAL EXPRESSION; PROGNOSTIC VALUE; DIFFERENTIAL EXPRESSION; PROTEIN EXPRESSION AB Two types of endometrial carcinoma (EC) have been delineated on the basis of clinicopathologic studies. Low-grade endometrioid carcinoma (EEC) is the prototype of type I EC and is characterized by microsatellite instability and PTEN, K-ras, and/or beta-catenin gene mutations, whereas type II EC is typically represented by serous and clear cell carcinomas (SCs/CCCs), the former frequently showing p53 mutations and c-erb-2 overexpression; however, the molecular profile of grade 3 EEC has not yet been well characterized. The goal of this study was to define the immunohistochemical and molecular profile of grade 3 EEC. We studied 25 patients with grade 3 EEC ranging in age from 35 to 87 (mean 61) years. At the time of initial diagnosis, 16 patients had stage I tumors, whereas 3, 5, and 1 had stages II, III, and IV tumors, respectively. Only 1 patient with stage IV tumor had disease in the peritoneum because of direct extend of tumor through the uterine wall. Two tissue microarrays were constructed from paraffin-embedded blocks and stained for MLH-1, MSH-2, p16, cyclin D1, C-erb-B2, WT-1, and p53. Loss of MLH-1 and MSH-2 was seen in 3 of 25 and 1 of 24 tumors, respectively; none showed loss of both. Diffuse p16 nuclear expression was found in 7 of 23 cases; diffuse and strong nuclear immunostaining for p53, cyclin D1, and Her-2 was seen in 9 of 24 neoplasms, 9 of 25, and 3 of 25 carcinomas, respectively. WT-1 was negative in all 25 tumors. One of the 3 grade 3 EECs with Her-2 overexpression showed gene amplification by fluorescence in situ hybridization analysis. No gene amplification for cyclin D1 was found. Followup information was available for all patients. Sixteen had stage I tumors. Of these patients, 11 were alive and well (AW), 3 died of disease (DOD), and 2 died of unrelated causes (DUC), with a mean follow-up time of 56 months (range, 24 to 96 mo); 2 of 3 patients with stage II tumors DOD, and 1 was AW with a mean follow-up time of 81 months (range, 6 to 66 mo); of the 5 patients with stage III tumors, 2 DOD, 1 was AW, 1 was alive with lung metastases, and 1 DUC [mean follow-up of 29 months (range, 12 to 74 mo)]; the only patient who had a stage IV tumor DOD 12 months later. Interestingly, patients with grade 3 EECs showing loss of MLH-1/MSH-2 had stage I tumors, and all were AW (60 to 84 mo). Seventy-seven percent (7 of 9) of patients with tumors showing cyclin D1 overexpression were stage I, and none died of disease, whereas 85% (6 of 7) of patients with p16-positive tumors were high stage (2 stage II, 3 stage III, and 1 stage IV), and 5 DOD. All but one of these patients had tumors that also had p53 overexpression. All 3 patients with Her-2 overexpression DOD (stages I, III, and IV). In conclusion, this study shows that grade 3 EEC shares with low-grade EEC the overexpression but not amplification of cyclin D1 and low frequency of Her-2 overexpression and amplification. Grade 3 EEC shares with SC the relatively common p53 and p16 overexpression and low frequency of loss of mismatch repair genes. However, in contrast to SC ECs, which often show WT-1, cyclin D1 amplification, and Her-2 overexpression and/or amplification, grade 3 EECs rarely overexpressed any of these markers. Moreover, in this study, patients with tumors showing loss of MLH-1/MSH-2 or cyclin D1 overexpression were more likely to have low-stage tumors (stage I), whereas patients with tumors that overexpressed p53, p16, or Her-2 were frequently associated with high-stage tumors. C1 [Oliva, Esther] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Wright Pathol Labs,Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gillette Ctr Oncol Gynecol, Boston, MA 02114 USA. RP Oliva, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Wright Pathol Labs,Dept Pathol, 55 Fruit St,Warren 251A, Boston, MA 02114 USA. EM eoliva@partners.org NR 88 TC 36 Z9 38 U1 0 U2 6 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 MAY PY 2012 VL 36 IS 5 BP 753 EP 761 DI 10.1097/PAS.0b013e318247b7bb PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 926EL UT WOS:000302814000014 PM 22498825 ER PT J AU Stahl, DL Groeben, H Kroepfl, D Gautam, S Eikermann, M AF Stahl, D. L. Groeben, H. Kroepfl, D. Gautam, S. Eikermann, M. TI Development and validation of a novel tool to estimate peri-operative blood loss* SO ANAESTHESIA LA English DT Article ID TRANSFUSION; PATIENT; MANAGEMENT; SURGERY; ANEMIA AB Surgical blood loss predicts peri-operative outcomes. We have developed and validated Blood Loss Scores to estimate peri-operative blood loss during major abdominal surgery. Surgical blood loss and changes in haemoglobin concentration were recorded intra- and postoperatively for 48 h in 100 patients undergoing radical prostatectomy. Data from the first group (n = 50) were used to derive the Blood Loss Scores which were validated against the data from a second group (n = 50) at three time points (immediately postoperative and 24- and 48-h later). The score, taking into account suction fluid volume and haemoglobin concentration, explained more of the variance in the measured blood loss than the experts assessment (77% vs 54%, p = 0.05) or the change in haemoglobin concentration (77% vs 11%, p < 0.0001). Addition of the change in haemoglobin concentration improved the estimate for the 24- and 48-h postoperative Blood Loss Scores to explain 78% and 80% of the variance of measured blood loss. C1 [Stahl, D. L.] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Groeben, H.] Klinikum Essen Mitte, Dept Anaesthesiol, Klin Anasthesiol Intensiv & Schmerztherapie, Essen, Germany. [Kroepfl, D.] Klinikum Essen Mitte, Dept Urol, Urol Klin, Essen, Germany. [Gautam, S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Eikermann, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Stahl, DL (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM dstahl@partners.org OI Kroepfl, Darko/0000-0002-8690-2093 FU Pfizer Inc. FX Dr Eikermann received an unrestricted grant for this investigator-initiated trial from Pfizer Inc. Dr Stahl, Dr. Groeben, Dr Kroepfel and Dr Gautam have no competing interests. NR 19 TC 12 Z9 13 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-2409 J9 ANAESTHESIA JI Anaesthesia PD MAY PY 2012 VL 67 IS 5 BP 479 EP 486 DI 10.1111/j.1365-2044.2011.06916.x PG 8 WC Anesthesiology SC Anesthesiology GA 923IU UT WOS:000302613800007 PM 22352443 ER PT J AU Bittner, EA George, E Eikermann, M Schmidt, U AF Bittner, E. A. George, E. Eikermann, M. Schmidt, U. TI Evaluation of the association between quality of handover and length of stay in the post anaesthesia care unit: a pilot study SO ANAESTHESIA LA English DT Letter ID CALL; ROOM C1 [Bittner, E. A.; George, E.; Eikermann, M.; Schmidt, U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bittner, EA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ebittner@partners.org NR 9 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-2409 J9 ANAESTHESIA JI Anaesthesia PD MAY PY 2012 VL 67 IS 5 BP 548 EP 549 DI 10.1111/j.1365-2044.2012.07091.x PG 2 WC Anesthesiology SC Anesthesiology GA 923IU UT WOS:000302613800024 PM 22493966 ER PT J AU Connors, JM Wiener-Kronish, JP AF Connors, Jean Marie Wiener-Kronish, Jeanine P. TI Continuing Aspirin in the Perioperative Patient SO ANNALS OF SURGERY LA English DT Editorial Material C1 [Connors, Jean Marie; Wiener-Kronish, Jeanine P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Brigham & Womens Hosp, Dept Anesthesia Crit Care & Pain Med,Div Hematol, Boston, MA 02114 USA. RP Wiener-Kronish, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Brigham & Womens Hosp, Dept Anesthesia Crit Care & Pain Med,Div Hematol, 55 Fruit St, Boston, MA 02114 USA. EM jwiener-kro-nish@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2012 VL 255 IS 5 BP 820 EP 820 DI 10.1097/SLA.0b013e3182505069 PG 1 WC Surgery SC Surgery GA 927VX UT WOS:000302939500012 PM 22504186 ER PT J AU In, H Neville, BA Lipsitz, SR Corso, KA Weeks, JC Greenberg, CC AF In, Haejin Neville, Bridget A. Lipsitz, Stuart R. Corso, Katherine A. Weeks, Jane C. Greenberg, Caprice C. TI The Role of National Cancer Institute-Designated Cancer Center Status Observed Variation in Surgical Care Depends on the Level of Evidence SO ANNALS OF SURGERY LA English DT Article ID SENTINEL LYMPH-NODE; SEER-MEDICARE DATA; III COLON-CANCER; AXILLARY DISSECTION; BREAST-CANCER; KNOWLEDGE TRANSLATION; ADJUVANT CHEMOTHERAPY; COMORBIDITY INDEX; BARIATRIC SURGERY; COLORECTAL-CANCER AB Objective: We sought to evaluate differences in guideline concordance between National Cancer Institute (NCI)-designated and other centers and determine whether the level of available evidence influences the degree of variation in concordance. Background: The National Cancer Institute recognizes centers of excellence in the advancement of cancer care. These NCI-designated cancer centers have been shown to have better outcomes for cancer surgery; however, little work has compared surgical process measures. Methods: A retrospective cohort study was conducted using Surveillance, Epidemiology and End Results registry linked to Medicare claims data. Fee-for-service Medicare patients with a definitive surgical resection for breast, colon, gastric, rectal, or thyroid cancers diagnosed between 2000 and 2005 were identified. Claims data from 1999 to 2006 were used. Our main outcome measure was guideline concordance at NCI-designated centers compared to other institutions, stratified by level of evidence as graded by National Comprehensive Cancer Network guideline panels. Results: All centers achieved at least 90%, and often 95%, concordance with guidelines based on level 1 evidence. Concordance rates for guidelines with lower-level evidence ranged from 30% to 97% and were higher at NCI-designated centers. The adjusted concordance ratios for category 1 guidelines were between 1.02 and 1.08, whereas concordance ratios for guidelines with lower-level evidence ranged from 0.97 to 2.19, primarily favoring NCI-designated centers. Conclusions: When strong evidence supports a guideline, there is little variation in practice between NCI-designated centers and other hospitals, suggesting that all are providing appropriate care. Variation in care may exist, however, for guidelines that are based on expert consensus rather than strong evidence. This suggests that future efforts to generate needed evidence on the optimal approach to care may also reduce institutional variation. C1 [In, Haejin; Lipsitz, Stuart R.; Corso, Katherine A.; Greenberg, Caprice C.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [In, Haejin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Neville, Bridget A.; Weeks, Jane C.; Greenberg, Caprice C.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Greenberg, CC (reprint author), Univ Wisconsin, Ctr Clin Sci, Wisconsin Surg Outcomes Res Program, 600 Highland Ave, Madison, WI 53792 USA. EM greenberg@surgery.wisc.edu FU American Surgical Association Foundation (Greenberg); NIH Gazelle (In) [R25 CA092203] FX This work was supported in part by a grant from the American Surgical Association Foundation (Greenberg) and by the "Program in Cancer Outcomes Research Training" grant (NIH R25 CA092203, Gazelle) (In). The sponsor did not have any role in design or conduct of the study or manuscript preparation or review. The authors report no financial conflicts of interest. NR 49 TC 18 Z9 18 U1 0 U2 2 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 MAY PY 2012 VL 255 IS 5 BP 890 EP 895 DI 10.1097/SLA.0b013e31824deae6 PG 6 WC Surgery SC Surgery GA 927VX UT WOS:000302939500022 PM 22504278 ER PT J AU Cuschieri, J Johnson, JL Sperry, J West, MA Moore, EE Minei, JP Bankey, PE Nathens, AB Cuenca, AG Efron, PA Hennessy, L Xiao, WZ Mindrinos, MN McDonald-Smith, GP Mason, PH Billiar, TR Schoenfeld, DA Warren, HS Cobb, JP Moldawer, LL Davis, RW Maier, RV Tompkins, RG AF Cuschieri, Joseph Johnson, Jeffrey L. Sperry, Jason West, Michael A. Moore, Ernest E. Minei, Joseph P. Bankey, Paul E. Nathens, Avery B. Cuenca, Alex G. Efron, Philip A. Hennessy, Laura Xiao, Wenzhong Mindrinos, Michael N. McDonald-Smith, Grace P. Mason, Philip H. Billiar, Timothy R. Schoenfeld, David A. Warren, H. Shaw Cobb, J. Perren Moldawer, Lyle L. Davis, Ronald W. Maier, Ronald V. Tompkins, Ronald G. CA Inflammation Host Response Injury TI Benchmarking Outcomes in the Critically Injured Trauma Patient and the Effect of Implementing Standard Operating Procedures SO ANNALS OF SURGERY LA English DT Article ID SCALE COLLABORATIVE PROJECT; ORIENTED RESEARCH CORE; SURVIVING SEPSIS CAMPAIGN; MULTIPLE ORGAN FAILURE; CLINICAL CARE; HOST RESPONSE; SEPTIC SHOCK; MECHANICAL VENTILATION; INFLAMMATION; GUIDELINES AB Objective: To determine and compare outcomes with accepted benchmarks in trauma care at 7 academic level I trauma centers in which patients were treated on the basis of a series of standard operating procedures (SOPs). Background: Injury remains the leading cause of death for those younger than 45 years. This study describes the baseline patient characteristics and well-defined outcomes of persons hospitalized in the United States for severe blunt trauma. Methods: We followed 1637 trauma patients from 2003 to 2009 up to 28 hospital days using SOPs developed at the onset of the study. An extensive database on patient and injury characteristics, clinical treatment, and outcomes was created. These data were compared with existing trauma benchmarks. Results: The study patients were critically injured and were in shock. SOP compliance improved 10% to 40% during the study period. Multiple organ failure and mortality rates were 34.8% and 16.7%, respectively. Time to recovery, defined as the time until the patient was free of organ failure for at least 2 consecutive days, was developed as a new outcome measure. There was a reduction in mortality rate in the cohort during the study that cannot be explained by changes in the patient population. Conclusions: This study provides the current benchmark and the overall positive effect of implementing SOPs for severely injured patients. Over the course of the study, there were improvements in morbidity and mortality rates and increasing compliance with SOPs. Mortality was surprisingly low, given the degree of injury, and improved over the duration of the study, which correlated with improved SOP compliance. C1 [Tompkins, Ronald G.] Harvard Univ, Sch Med, MGH Burn Serv, SHC Boston,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schoenfeld, David A.; Warren, H. Shaw; Cobb, J. Perren; Tompkins, Ronald G.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Cuschieri, Joseph; Maier, Ronald V.] Univ Washington, Sch Med, Seattle, WA USA. [Cuschieri, Joseph; Hennessy, Laura; Maier, Ronald V.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Johnson, Jeffrey L.; Moore, Ernest E.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Johnson, Jeffrey L.; Moore, Ernest E.] Denver Hlth Med Ctr, Denver, CO USA. [Sperry, Jason; Billiar, Timothy R.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Sperry, Jason; Billiar, Timothy R.] Presbyterian Univ Hosp, Pittsburgh, PA 15213 USA. [West, Michael A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [West, Michael A.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Minei, Joseph P.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Minei, Joseph P.] Parkland Hlth & Hosp Syst, Dallas, TX USA. [Bankey, Paul E.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Bankey, Paul E.] Univ Rochester, Strong Mem Hosp, Rochester, NY 14642 USA. [Nathens, Avery B.] Univ Toronto, Toronto, ON, Canada. [Nathens, Avery B.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Cuenca, Alex G.; Efron, Philip A.; Moldawer, Lyle L.] Univ Florida, Coll Med, Gainesville, FL USA. [Cuenca, Alex G.; Efron, Philip A.; Moldawer, Lyle L.] Univ Florida, Shands Hosp, Gainesville, FL USA. [Mindrinos, Michael N.; Davis, Ronald W.] Stanford Genome Technol Ctr, Palo Alto, CA USA. RP Tompkins, RG (reprint author), Harvard Univ, Sch Med, MGH Burn Serv, SHC Boston,Massachusetts Gen Hosp, 55 Fruit St,GRB 1302, Boston, MA 02114 USA. EM rtomp-kins@partners.org OI xiao, wenzhong/0000-0003-4944-6380 FU National Institute of General Medical Sciences [2 U54 GM 062119] FX This study was supported by The Inflammation and the Host Response to Injury Large Scale Collaborative Research Grant from the National Institute of General Medical Sciences, 2 U54 GM 062119. NR 38 TC 38 Z9 38 U1 1 U2 9 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 MAY PY 2012 VL 255 IS 5 BP 993 EP 999 DI 10.1097/SLA.0b013e31824f1ebc PG 7 WC Surgery SC Surgery GA 927VX UT WOS:000302939500038 PM 22470077 ER PT J AU Mitsani, D Nguyen, MH Shields, RK Toyoda, Y Kwak, EJ Silveira, FP Pilewski, JM Crespo, MM Bermudez, C Bhama, JK Clancy, CJ AF Mitsani, Dimitra Nguyen, M. Hong Shields, Ryan K. Toyoda, Yoshiya Kwak, Eun J. Silveira, Fernanda P. Pilewski, Joseph M. Crespo, Maria M. Bermudez, Christian Bhama, Jay K. Clancy, Cornelius J. TI Prospective, Observational Study of Voriconazole Therapeutic Drug Monitoring among Lung Transplant Recipients Receiving Prophylaxis: Factors Impacting Levels of and Associations between Serum Troughs, Efficacy, and Toxicity SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; STEM-CELL TRANSPLANTATION; ADVERSE EVENTS; CANINE LUNG; SAFETY; PHARMACOKINETICS; ASPERGILLOSIS; POPULATION; ABNORMALITIES; DEFINITIONS AB Voriconazole prophylaxis is common following lung transplantation, but the value of therapeutic drug monitoring is unknown. A prospective, observational study of lung transplant recipients (n = 93) receiving voriconazole prophylaxis was performed. Serum voriconazole troughs (n = 331) were measured by high-pressure liquid chromatography. The median initial and subsequent troughs were 1.91 and 1.46 mu g/ml, respectively. The age of the patient directly correlated with initial troughs (P = 0.005). Patients that were >= 60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs, respectively. In 95% (88/93) of patients,>= 2 troughs were measured. In 28% (25/88) and 32% (28/88) of these patients, all troughs were <= 1.5 mu g/ml or > 1.5 mu g/ml, respectively. Ten percent (10/93) and 27% (25/93) of the patients developed invasive fungal infection (tracheobronchitis) and fungal colonization, respectively. The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 mu g/ml (P = 0.07). Invasive fungal infections or colonization were more likely with troughs of <= 1.5 mu g/ml (P = 0.01) and among patients with no trough of > 1.5 mu g/ml (P = 0.007). Other cutoff troughs correlated less strongly with microbiologic outcomes. Troughs correlated directly with aspartate transferase levels (P = 0.003), but not with other liver enzymes. Voriconazole was discontinued due to suspected toxicity in 27% (25/93) of the patients. The troughs did not differ at the times of suspected drug-induced hepatotoxicity, central nervous system (CNS) toxicity, or nausea/vomiting and in the absence of toxicity. Voriconazole prophylaxis was most effective at troughs of > 1.5 mu g/ml. A cutoff for toxicity was not identified, but troughs of > 4 mu g/ml were rare. The data support a target range of > 1.5 to 4 mu g/ml. C1 [Mitsani, Dimitra; Nguyen, M. Hong; Shields, Ryan K.; Kwak, Eun J.; Silveira, Fernanda P.; Clancy, Cornelius J.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA 15260 USA. [Pilewski, Joseph M.; Crespo, Maria M.] Univ Pittsburgh, Div Pulm Med, Dept Med, Pittsburgh, PA USA. [Toyoda, Yoshiya; Bermudez, Christian; Bhama, Jay K.] Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Nguyen, MH (reprint author), Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA 15260 USA. EM mhn5@pitt.edu FU Pfizer; Merck; Astellas; ViraCor-IBT Laboratories FX Funding for this project was provided through an investigator-initiated research grant from Pfizer to C. J. Clancy. Pfizer had no input into the study design, data interpretation, or conclusions. C. J. Clancy has received grant support for unrelated research projects from Pfizer, Merck, and Astellas. M. H. Nguyen has received grant support for unrelated research projects from Pfizer, Merck, and ViraCor-IBT Laboratories. R. K. Shields has received grant support for unrelated research projects from Merck and Astellas. E. J. Kwak has received grant support for unrelated research projects from Pfizer. NR 41 TC 50 Z9 53 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2012 VL 56 IS 5 BP 2371 EP 2377 DI 10.1128/AAC.05219-11 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 925VQ UT WOS:000302790400023 PM 22330924 ER PT J AU Salanitro, AH Ritchie, CS Hovater, M Roth, DL Sawyer, P Locher, JL Bodner, E Brown, CJ Allman, RM AF Salanitro, Amanda H. Ritchie, Christine S. Hovater, Martha Roth, David L. Sawyer, Patricia Locher, Julie L. Bodner, Eric Brown, Cynthia J. Allman, Richard M. TI Inflammatory biomarkers as predictors of hospitalization and death in community-dwelling older adults SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE Inflammation; Hospitalization; Mortality; Community-dwelling older adults ID FUNCTIONAL DECLINE; AFRICAN-AMERICAN; BODY-COMPOSITION; MARKERS; MORTALITY; RISK; HEALTH; ELDERS; ASSOCIATIONS; CHOLESTEROL AB Individuals with multimorbidity may be at increased risk of hospitalization and death. Comorbidity indexes do not capture severity of illness or healthcare utilization; however, inflammation biomarkers that are not disease-specific may predict hospitalization and death in older adults. We sought to predict hospitalization and mortality of older adults using inflammation biomarkers. From a prospective, observational study, 370 community-dwelling adults 65 years or older from central Alabama participated in an in-home assessment and provided fasting blood samples for inflammation biomarker testing in 2004. We calculated an inflammation summary score (range 0-4), one point each for low albumin, high C-reactive protein, low cholesterol, and high interleukin-6. Utilizing Cox proportional hazards models, inflammation summary scores were used to predicted time to hospitalization and death during a 4-year follow up period. The mean age was 73.7 (+/- 5.9 yrs), and 53 (14%) participants had summary scores of 3 or 4. The rates of dying were significantly increased for participants with inflammation summary scores of 2, 3, or 4 (hazard ratio (HR) 2.22, 2.78, and 7.55, respectively; p < 0.05). An inflammation summary score of 4 significantly predicted hospitalization (HR 5.92, p < 0.05). Community-dwelling older adults with biomarkers positive for inflammation had increased rates of being hospitalized or dying during the follow up period. Assessment of the individual contribution of particular inflammation biomarkers in the prediction of health outcomes in older populations and the development of validated summary scores to predict morbidity and mortality are needed. Published by Elsevier Ireland Ltd. C1 [Salanitro, Amanda H.] Vanderbilt Univ, Sect Hosp Med, Nashville, TN 37212 USA. [Salanitro, Amanda H.] Vanderbilt Univ, VA Tennessee Valley Healthcare Geriatr Res Educ C, Nashville, TN 37212 USA. [Ritchie, Christine S.; Sawyer, Patricia; Locher, Julie L.; Bodner, Eric; Brown, Cynthia J.; Allman, Richard M.] Univ Alabama, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [Ritchie, Christine S.; Roth, David L.; Brown, Cynthia J.; Allman, Richard M.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Ritchie, Christine S.; Roth, David L.; Brown, Cynthia J.; Allman, Richard M.] Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, Birmingham, AL 35294 USA. [Hovater, Martha; Roth, David L.] Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. RP Salanitro, AH (reprint author), Room A-414,1310 24th Ave S, Nashville, TN 37212 USA. EM Amanda.Salanitro@Vanderbilt.Edu FU National Institute on Aging (NIA) [R01-AG015062, P30AG031054, 1K07AG31779]; American Cancer Society; AHRQ; NIH [1UL 1RR025777]; HRSA; Donald W. Reynolds Foundation; UpToDate; Department of Veterans Affairs Health Services Research & Development Service [E6326W]; GCRC from the National Center for Research Resources [M01 RR-00032] FX CJB was a member of the editorial board for JAGS. DLR, JLL, RMA were received the grant funding from National Institute on Aging (NIA). JLL was received the grant funding from American Cancer Society. CSR was employment at UAB, Birmingham VA Medical Center; grants/funds from AHRQ, NIH, HRSA, Donald W. Reynolds Foundation; honoraria from Center to Advance Palliative Care, Macon State College, & American Board of Internal Medicine; consultant for University of Puerto Rico; royalties from UpToDate; member of American Academy of Hospice & Palliative Medicine Board of Directors.; This work was supported by the National Institute on Aging [grant numbers R01-AG015062, P30AG031054] to RMA; the National Institute on Aging [grant number 1K07AG31779] to CSR; and the Department of Veterans Affairs Health Services Research & Development Service, Research Career Development Award [grant number E6326W] to CJB; and the National Institutes of Health grant award 1UL 1RR025777 partially supported RMA. Blood analyses supported by GCRC Grant M01 RR-00032 from the National Center for Research Resources. The funding sources had no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; nor in the decision to submit the manuscript for publication. NR 32 TC 11 Z9 11 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD MAY-JUN PY 2012 VL 54 IS 3 BP E387 EP E391 DI 10.1016/j.archger.2012.01.006 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 928DB UT WOS:000302959400021 PM 22305611 ER PT J AU Hobson, DTG Imudia, AN Al-Safi, ZA Shade, G Kruger, M Diamond, MP Awonuga, AO AF Hobson, Deslyn T. G. Imudia, Anthony N. Al-Safi, Zain A. Shade, George Kruger, Michael Diamond, Michael P. Awonuga, Awoniyi O. TI Comparative analysis of different laparoscopic hysterectomy procedures SO ARCHIVES OF GYNECOLOGY AND OBSTETRICS LA English DT Article DE Laparoscopic hysterectomy; Laparoscopic supracervical hysterectomy; Total laparoscopic hysterectomy; Laparoscopic-assisted vaginal hysterectomy ID ASSISTED VAGINAL HYSTERECTOMY; SUPRACERVICAL HYSTERECTOMY; UNITED-STATES; PEROPERATIVE ELECTROCOAGULATION; ABDOMINAL HYSTERECTOMY; ENDOCERVICAL MUCOSA; CERVICAL STUMP; BENIGN DISEASE; SERIES; CARCINOMA AB To compare the antecedent gynecological characteristics, indications for, and complications associated with, the different laparoscopic approaches to hysterectomy, in women with benign gynecological conditions. A retrospective cohort study of 957 patients who underwent laparoscopic supracervical (LSH), total (TLH), and assisted vaginal (LAVH) hysterectomies between January 2003 and December 2009. Among 957 LH, 799 (83.5%) were LSH, 62 (6.4%) TLH, and 96 (10.1%) LAVH. Demographic characteristics were not different among the groups. Antecedent gynecologic conditions that were associated with the type of laparoscopic hysterectomy (LH) performed were: postmenopausal bleeding [LAVH vs. LSH, odds ratio (OR) 2.20; 95% confidence interval (CI) 1.04-4.65], previous pelvic surgery (TLH vs. LSH, OR 1.92; CI 1.05-3.52), previous cesarean delivery (LAVH vs. LSH, OR 0.39; CI 0.21-0.76), and prior hysteroscopy (LAVH vs. LSH, OR 0.29; CI 0.16-0.50). Preoperative diagnoses that were associated with the choice of LH were: menometrorrhagia (LAVH vs. LSH, OR 0.23; CI 0.14-0.38; TLH vs. LSH, OR 0.50; CI 0.26-0.98), uterine fibroids (LAVH vs. LSH, OR 0.25; CI 0.15-0.41), endometrial hyperplasia (TLH vs. LSH, OR 5.5; CI 2.04-14.84), and cervical dysplasia (TLH vs. LSH, OR 17.1; CI 6.83-42.79; LAVH vs. LSH, OR 8.05; CI 3.05-22.06). Estimated blood loss, operating time, and length of hospital stay were significantly reduced with LSH. Antecedent gynecological history and the indications for surgery were associated with the type of LH performed in our institution. LSH was the most common approach and was associated with significantly less morbidity. C1 [Hobson, Deslyn T. G.; Al-Safi, Zain A.; Shade, George; Diamond, Michael P.; Awonuga, Awoniyi O.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit Med Ctr, Detroit, MI 48201 USA. [Imudia, Anthony N.] Massachusetts Gen Hosp, Div Reprod Med, Boston, MA 02114 USA. [Imudia, Anthony N.] Massachusetts Gen Hosp, IVF, Boston, MA 02114 USA. [Kruger, Michael] Wayne State Univ, Sch Med, CS Mott Ctr Human Growth & Dev, Detroit, MI 48201 USA. [Diamond, Michael P.; Awonuga, Awoniyi O.] Wayne State Univ, Sch Med, Div Reprod Endocrinol & Infertil, Detroit Med Ctr, Detroit, MI 48201 USA. RP Hobson, DTG (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit Med Ctr, 3990 John R St, Detroit, MI 48201 USA. EM hdeslyn@hotmail.com OI Diamond, Michael/0000-0001-6353-4489 NR 35 TC 12 Z9 14 U1 0 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0932-0067 J9 ARCH GYNECOL OBSTET JI Arch. Gynecol. Obstet. PD MAY PY 2012 VL 285 IS 5 BP 1353 EP 1361 DI 10.1007/s00404-011-2140-2 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 926EN UT WOS:000302814200023 PM 22124531 ER PT J AU Schlett, CL Ferencik, M Kriegel, MF Bamberg, F Ghoshhajra, BB Joshi, SB Nagurney, JT Fox, CS Truong, QA Hoffmann, U AF Schlett, Christopher L. Ferencik, Maros Kriegel, Matthias F. Bamberg, Fabian Ghoshhajra, Brian B. Joshi, Subodh B. Nagurney, John T. Fox, Caroline S. Truong, Quynh A. Hoffmann, Udo TI Association of pericardial fat and coronary high-risk lesions as determined by cardiac CT SO ATHEROSCLEROSIS LA English DT Article DE Coronary artery disease; Cardiac CT angiography; Peri-cardial fat; Adipose tissue; Vulnerable plaque; High-risk lesions ID EPICARDIAL ADIPOSE-TISSUE; MULTIDETECTOR COMPUTED-TOMOGRAPHY; VISCERAL ABDOMINAL FAT; ACUTE CHEST-PAIN; ARTERY-DISEASE; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUE; NONINVASIVE ASSESSMENT; ANGIOGRAPHY; CALCIFICATION AB Objective: Pericardial adipose tissue (PAT) is a pathogenic fat depot associated with coronary atherosclerosis and cardiovascular events. We hypothesized that higher PAT is associated with coronary high-risk lesions as determined by cardiac CT. Methods: We included 358 patients (38% female; median age 51 years) who were admitted to the ED with acute chest pain and underwent 64-slice CT angiography. The cardiac CT data sets were assessed for presence and morphology of CAD and PAT. Coronary high-risk lesions were defined as >50% luminal narrowing and at least two of the following characteristics: positive remodeling, low-density plaque, and spotty calcification. PAT was defined as any pixel with CT attenuation of -190 to -30 HU within the pericardial sac. Results: Based on cardiac CT, 50% of the patients (n = 180) had no CAD, 46% (n = 165) had CAD without high-risk lesions, and 13 patients had CAD with high-risk lesions. The median PAT in patients with high-risk lesions was significantly higher compared to patients without high-risk lesions and without any CAD (151.9 [109.0-179.4] cm(3) vs. 110.0 [81.5-137.4] cm(3), vs. 74.8 [58.2-111.7] cm(3), respectively p = 0.04 and p < 0.0001). These differences remained significant after adjusting for traditional risk factors including BMI (all p < 0.05). The area under the ROC curve for the identification of high-risk lesions was 0.756 in a logistic regression model with PAT as a continuous predictor. Conclusion: PAT volume is nearly twice as high in patients with high-risk coronary lesions as compared to those without CAD. PAT volume is significantly associated with high risk coronary lesion morphology independent of clinical characteristics and general obesity. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Schlett, Christopher L.; Ghoshhajra, Brian B.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Ferencik, Maros; Truong, Quynh A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Schlett, Christopher L.; Ferencik, Maros; Kriegel, Matthias F.; Ghoshhajra, Brian B.; Joshi, Subodh B.; Nagurney, John T.; Fox, Caroline S.; Truong, Quynh A.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bamberg, Fabian] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-81377 Munich, Germany. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. EM uhoffmann@partners.org RI 王, 强/F-4212-2011 FU NHLBI NIH HHS [L30 HL093806, K23 HL098370] NR 42 TC 25 Z9 25 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2012 VL 222 IS 1 BP 129 EP 134 DI 10.1016/j.atherosclerosis.2012.02.029 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 928DJ UT WOS:000302960600020 PM 22417843 ER PT J AU Perera, MN Ganesan, V Siskind, LJ Szulc, ZM Bielawski, J Alicja, B Bittman, R Colombini, M AF Perera, Meenu N. Ganesan, Vidyaramanan Siskind, Leah J. Szulc, Zdzislaw M. Bielawski, Jacek Alicja, Bielawska Bittman, Robert Colombini, Marco TI Ceramide channels: Influence of molecular structure on channel formation in membranes SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE Ceramide; Analogs; Channels; Mitochondria; Permeabilization; Pore ID MITOCHONDRIAL OUTER-MEMBRANE; TANDEM MASS-SPECTROMETRY; BIOACTIVE SPHINGOLIPIDS; SUBSTRATE-SPECIFICITY; QUANTITATIVE-ANALYSIS; PLANT-MITOCHONDRIA; ESTER PRECURSORS; LIPID-BILAYERS; SPHINGOSINE; PROTEINS AB The sphingolipid, ceramide, self-assembles in the mitochondrial outer membrane (MOM), forming large channels capable of translocating proteins. These channels are believed to be involved in protein release from mitochondria, a key decision-making step in cell death. Synthetic analogs of ceramide, bearing modifications in each of the major structural features of ceramide were used to probe the molecular basis for the stability of ceramide channels. Channel stability and mitochondrial permeabilization were disrupted by methylation of the C1-hydroxyl group whereas modifications of the C3 allylic hydroxyl group were well tolerated. A change in chirality at C2 that would influence the orientation of the C1-hydroxyl group resulted in a strong reduction of channel-forming ability. Similarly, methylation of the amide nitrogen is also detrimental to channel formation. Many changes in the degree, location and nature of the unsaturation of ceramide had little effect on mitochondrial permeabilization. Competition experiments between ceramide and analogs resulted in synergy with structures compatible with the ceramide channel model and antagonism with incompatible structures. The results are consistent with ceramide channels being highly organized structures, stabilized by specific inter-molecular interactions, similar to the interactions responsible for protein folding. (C) 2012 Elsevier B.V. All rights reserved. C1 [Perera, Meenu N.; Ganesan, Vidyaramanan; Colombini, Marco] Univ Maryland, Dept Biol, College Pk, MD 20742 USA. [Siskind, Leah J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Siskind, Leah J.; Szulc, Zdzislaw M.; Bielawski, Jacek; Alicja, Bielawska] Med Univ S Carolina, Charleston, SC 29403 USA. [Bittman, Robert] CUNY Queens Coll, Flushing, NY 11367 USA. RP Colombini, M (reprint author), Univ Maryland, Dept Biol, College Pk, MD 20742 USA. EM colombini@umd.edu RI Colombini, Marco/A-1540-2014; Ganesan, Vidyaramanan/H-3787-2016; OI Ganesan, Vidyaramanan/0000-0002-6160-5594; Szulc, Zdzislaw M./0000-0003-1756-9028 FU National Science Foundation [MCB-1023008]; National Institutes of Health [HL-083187]; Veterans Administration; Veteran's Administration REAP; NCI [IPO1CA097132, P30 CA 138313]; NIH/NCRR [P20 RR017677]; NIH from National Center for Research Resources [C06 RR018823] FX This work was supported by grants from the National Science Foundation [MCB-1023008] to MC and from the National Institutes of Health [HL-083187] to RB. L.J.S is supported by a Career Development Award-2 from the Veterans Administration and pilot project funding from a Veteran's Administration REAP. Synthetic lipids and LC-MS/MS analysis of sphingolipids were provided by the Lipidomics Shared Resource, MUSC, supported by NCI Grants: [IPO1CA097132] and [P30 CA 138313] and NIH/NCRR SC COBRE Grant [P20 RR017677]. Laboratory space for Lipidomics Shared Resource in the CRI building of MUSC was supported by NIH Grant [C06 RR018823] from the Extramural Research Facilities Program of the National Center for Research Resources. NR 45 TC 22 Z9 23 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD MAY PY 2012 VL 1818 IS 5 BP 1291 EP 1301 DI 10.1016/j.bbamem.2012.02.010 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 928GL UT WOS:000302971100021 PM 22365970 ER PT J AU Deatrick, JA Hardie, T AF Deatrick, Janet A. Hardie, Thomas TI Strategies for Selecting Measures for Pediatric and Maternal Child Research SO CLINICAL NURSING RESEARCH LA English DT Editorial Material C1 [Deatrick, Janet A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Hardie, Thomas] Drexel Univ, Philadelphia, PA 19104 USA. RP Deatrick, JA (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Claire M Fagin Hall,418 Curie Blvd,223 2L, Philadelphia, PA 19104 USA. EM deatrick@nursing.upenn.edu RI Hardie, Thomas/J-7776-2012; OI Hardie, Thomas/0000-0002-4547-7991 NR 10 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1054-7738 J9 CLIN NURS RES JI Clin. Nurs. Res. PD MAY PY 2012 VL 21 IS 2 SI SI BP 135 EP 141 DI 10.1177/1054773812439511 PG 7 WC Nursing SC Nursing GA 926TL UT WOS:000302854600001 PM 22508686 ER PT J AU Chung, J Chen, CY Paw, BH AF Chung, Jacky Chen, Caiyong Paw, Barry H. TI Heme metabolism and erythropoiesis SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE anemia; iron; porphyrins; transporters ID CELLULAR IRON HOMEOSTASIS; ERYTHROID-DIFFERENTIATION; SIDEROBLASTIC ANEMIA; MICROCYTIC ANEMIA; MOLECULAR-BASIS; NULL ALLELES; PROTEIN; IDENTIFICATION; GENE; TRANSPORTER AB Purpose of review Heme biosynthesis requires a series of enzymatic reactions that take place in the cytosol and the mitochondria as well as the proper intercellular and intracellular trafficking of iron. Heme can also be acquired by intestinal absorption and intercellular transport. The purpose of this review is to highlight recent work on heme and iron transport with an emphasis on their relevance in erythropoiesis. Recent findings Whereas the enzymes responsible for heme biosynthesis have been identified, transport mechanisms for iron, heme, or heme synthesis intermediates are only emerging. Recent studies have shed light on how these molecules are transported among various cellular compartments, as well as tissues. Much of this progress can be attributed to the use of model organisms such as S. cerevisiae, C. elegans, D. rerio, and M. musculus. Genetic studies in these models have led to the identification of several new genes involved in heme metabolism. Although our understanding has greatly improved, it is highly likely that other regulators exist and additional work is required to characterize the pathways by which heme and iron are transported within the erythron. Summary The identification of heme and iron transport mechanisms will improve our understanding of blood development and provide new insight into human blood disorders. C1 [Chung, Jacky; Chen, Caiyong; Paw, Barry H.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Chung, Jacky; Chen, Caiyong; Paw, Barry H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Chung, Jacky; Chen, Caiyong; Paw, Barry H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Chung, Jacky; Chen, Caiyong; Paw, Barry H.] Harvard Univ, Sch Med, Boston, MA USA. RP Paw, BH (reprint author), BWH Hematol, 1 Blackfan Circle,Karp Res Bldg, Boston, MA 02115 USA. EM bpaw@rics.bwh.harvard.edu FU Canadian Institutes of Health Research; Cooley's Anemia Foundation; March of Dimes Foundation; National Institutes of Health [R01 DK070838, P01 HL032262] FX The work was supported in part by grants from the Canadian Institutes of Health Research (J.C.), the Cooley's Anemia Foundation (C.C.), the March of Dimes Foundation (B.H.P.), and the National Institutes of Health grants R01 DK070838 and P01 HL032262 (B.H.P.). NR 68 TC 20 Z9 21 U1 2 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAY PY 2012 VL 19 IS 3 BP 156 EP 162 DI 10.1097/MOH.0b013e328351c48b PG 7 WC Hematology SC Hematology GA 925UR UT WOS:000302787700004 PM 22406824 ER PT J AU Cesano, A Rosen, DB O'Meara, P Putta, S Gayko, U Spellmeyer, DC Cripe, LD Sun, ZX Uno, H Litzow, MR Tallman, MS Paietta, E AF Cesano, Alessandra Rosen, David B. O'Meara, Pat Putta, Santosh Gayko, Urte Spellmeyer, David C. Cripe, Larry D. Sun, Zhuoxin Uno, Hajime Litzow, Mark R. Tallman, Martin S. Paietta, Elisabeth TI Functional pathway analysis in acute myeloid leukemia using single cell network profiling assay: Effect of specimen source (bone marrow or peripheral blood) on assay readouts SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE cell signaling; acute myeloid leukemia; multiparameter analysis; flow cytometry; standardization; single cell network profiling; diagnostic; specimen source ID ACUTE MYELOGENOUS LEUKEMIA; NORMAL CYTOGENETICS; FLOW-CYTOMETRY; GENE-MUTATIONS; GROUP-B; FAVORABLE PROGNOSIS; SIGNALING NETWORKS; NORMAL KARYOTYPE; C-KIT; CANCER AB Background: Single cell network profiling (SCNP) is used to simultaneously measure the effects of modulators on signaling networks at the single cell level. SCNP-based biomarker assays predictive of response to induction therapy and relapse risk in acute myeloid leukemia (AML) patients are being developed. Such assays have typically used bone marrow (BM) as the sample source of blasts. Because circulating peripheral blasts are detectable in 65% of AML patients and peripheral blood (PB) sampling is less invasive than BM sampling, this study was performed to assess the effect of sample source on AML blasts signaling as measured in SCNP assay. Methods: SCNP using multiparametric flow cytometry was used to evaluate the activation state of intracellular signaling molecules in leukemic blasts under basal conditions and after treatment with modulators in 46 pairs of BM mononuclear cells/PB mononuclear cells. The relationship between readouts of modulated intracellular proteins ("nodes'') was measured using linear regression, Bland-Altman method, and Lin's concordance correlation coefficient. Results: The majority (156/161) of signaling nodes show strong correlations between paired PB and BM samples independently from the statistical method used. Notable exceptions were two PB samples with almost undetectable levels of circulating blasts compared with paired BM samples. Conclusions: Our results demonstrate that specimen source (BM or PB) does not significantly affect proteomic signaling in patients with AML and circulating blasts. The ability to use PB as a sample source will facilitate the monitoring of cellular signaling effects following administration of targeted therapies and at time points when BM aspirates are not clinically justifiable. (C) 2012 International Clinical Cytometry Society C1 [Cesano, Alessandra; Gayko, Urte] Nodality Inc, Clin Affairs, San Francisco, CA 94080 USA. [Rosen, David B.] Nodality Inc, Res, San Francisco, CA 94080 USA. [O'Meara, Pat; Putta, Santosh; Spellmeyer, David C.] Nodality Inc, Biostat & Bioinformat, San Francisco, CA 94080 USA. [Cripe, Larry D.] Indiana Univ, Eastern Cooperat Oncol Grp, Indianapolis, IN 46204 USA. [Sun, Zhuoxin; Uno, Hajime] Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA. [Litzow, Mark R.] Mayo Clin, Eastern Cooperat Oncol Grp, Rochester, MN USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Eastern Cooperat Oncol Grp, New York, NY 10021 USA. [Paietta, Elisabeth] Montefiore Med Ctr, North Div, Eastern Cooperat Oncol Grp, Bronx, NY 10467 USA. RP Cesano, A (reprint author), Nodality Inc, Clin Affairs, 170 Harbor Way,Suite 200, San Francisco, CA 94080 USA. EM alessandra.cesano@nodality.com FU NCI NIH HHS [U10 CA013650, P30 CA082709, U10 CA014958, U10 CA017145, U10 CA021115, U10 CA023318, U10 CA049883, U10 CA066636, U24 CA114737] NR 33 TC 18 Z9 18 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD MAY PY 2012 VL 82B IS 3 BP 158 EP 172 DI 10.1002/cyto.b.21007 PG 15 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 927VA UT WOS:000302937200007 PM 22334473 ER PT J AU Nagy, N Burns, AJ Goldstein, AM AF Nagy, Nandor Burns, Alan J. Goldstein, Allan M. TI Immunophenotypic characterization of enteric neural crest cells in the developing avian colorectum SO DEVELOPMENTAL DYNAMICS LA English DT Article DE enteric nervous system; Hirschsprung's disease; gut development; chick ID NERVOUS-SYSTEM; GASTROINTESTINAL-TRACT; HIRSCHSPRUNGS-DISEASE; SUBMUCOUS PLEXUS; WAVE-FRONT; MOUSE GUT; MIGRATION; INTESTINE; HINDGUT; NEURONS AB Background: The enteric nervous system (ENS) develops from neural crest-derived cells that migrate along the intestine to form two plexuses of neurons and glia. While the major features of ENS development are conserved across species, minor differences exist, especially in the colorectum. Given the embryologic and disease-related importance of the distal ENS, the aim of this study was to characterize the migration and differentiation of enteric neural crest-derived cells (ENCCs) in the colorectum of avian embryos. Results: Using normal chick embryos and vagal neural tube transplants from green fluorescent protein (GFP) -transgenic chick embryos, we find ENCCs entering the colon at embryonic day (E) 6.5, with colonization complete by E8. Undifferentiated ENCCs at the wavefront express HNK-1, N-cadherin, Sox10, p75, and L1CAM. By E7, differentiation begins in the proximal colon, with L1CAM and Sox10 becoming restricted to neuronal and glial lineages, respectively. By E8, multiple markers of differentiation are expressed along the entire colorectum. Conclusions: Our results establish the pattern of ENCC migration and differentiation in the chick colorectum, demonstrate the conservation of marker expression across species, highlight a range of markers, including neuronal cell adhesion molecules, which label cells at the wavefront, and provide a framework for future studies in avian ENS development. Developmental Dynamics 241:842851, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Nagy, Nandor; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Surg, Sch Med, Boston, MA 02114 USA. [Nagy, Nandor] Semmelweis Univ, Dept Human Morphol & Dev Biol, Fac Med, Budapest, Hungary. [Burns, Alan J.] UCL Inst Child Hlth, Neural Dev Unit, London, England. [Burns, Alan J.] UCL Inst Child Hlth, Gastroenterol Unit, London, England. RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Surg, Sch Med, Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org RI Burns, Alan/C-4988-2008 FU NIH [R01DK080914]; NICHD; Biotechnology and Biological Sciences Research Council (BBSRC); Wellcome Trust; Hungarian Academy of Sciences; EMBO FX Grant sponsor: NIH; Grant number: R01DK080914.; We thank Louis Reichardt and Thomas Muller for anti-chick p75NTR and B-fabp antibody, and Michael Wegner for Sox10 antibody. Monoclonal antibodies 4d (developed by Urs Rutishauser), 4H6 (developed by Willi Halfter), 8D9 (developed by Vance Lemmon), 6B3 (developed by Karen A. Knudsen) were obtained from the Developmental Studies Hybridoma Bank, developed under the auspices of the NICHD and maintained by the University of Iowa. Fertilized GFP chicken eggs were supplied by Prof. Helen Sang, The Roslin Institute, University of Edinburgh, from projects supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust. A.M.G. is supported by the NIH. N.N. is supported by a Bolyai Fellowship of the Hungarian Academy of Sciences and a Short-Term Fellowship from EMBO. NR 47 TC 12 Z9 12 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAY PY 2012 VL 241 IS 5 BP 842 EP 851 DI 10.1002/dvdy.23767 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 926VY UT WOS:000302861200002 PM 22411589 ER PT J AU Mordes, DA Brachtel, EF AF Mordes, Daniel A. Brachtel, Elena F. TI Cytopathology of subacute thyroiditis SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article C1 [Brachtel, Elena F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brachtel, EF (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St WRN 2, Boston, MA 02114 USA. EM ebrachtel@partners.org NR 3 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD MAY PY 2012 VL 40 IS 5 BP 433 EP 434 DI 10.1002/dc.21847 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 927KS UT WOS:000302906900011 PM 22045514 ER PT J AU Fromson, JA Sutton-Skinner, KM Gorrindo, T Baer, L Romeo, SA Rieu-Werden, ML Birnbaum, RJ AF Fromson, John A. Sutton-Skinner, Kelly M. Gorrindo, Tristan Baer, Lee Romeo, Sarah A. Rieu-Werden, Meghan L. Birnbaum, Robert J. TI Attention to body mass index by child psychiatry providers when prescribing second-generation antipsychotic medication to children: a survey study using a clinical vignette SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Article DE adverse effect; antipsychotic agent; body mass index; child psychiatry; guideline adherence ID WEIGHT-GAIN; RISPERIDONE; ADOLESCENTS; OLANZAPINE; QUALITY; RISK AB Aim: We sought to determine whether weight and body mass index measurement were taken into consideration when prescribing second-generation antipsychotic (SGA) medication to a child. Methods: Two hundred clinicians were surveyed using a hypothetical clinical case vignette at a child psychopharmacology, postgraduate medical education course. The vignette described an overweight 10-year-old boy who was about to be prescribed an SGA medication to control psychotic symptoms. The reference to the patient's being ` overweight' was purposefully included to determine if providers would assess the patient's risk of morbidity from the metabolic side effects of the SGAs at the time of prescribing. Results: Only 7.0% of prescribers listed either ` body mass index' or a combination of ` height' and ` weight' as part of their next treatment steps for an overweight child before prescribing an SGA. Conclusions: These results suggest the need for education as to the importance of body mass index monitoring when prescribing secondgeneration antipsychotic medications to children. C1 [Fromson, John A.; Sutton-Skinner, Kelly M.; Gorrindo, Tristan; Baer, Lee; Romeo, Sarah A.; Rieu-Werden, Meghan L.; Birnbaum, Robert J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fromson, John A.; Gorrindo, Tristan; Baer, Lee; Birnbaum, Robert J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Fromson, JA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM jfromson@partners.org FU Astra Zeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Eli Lilly; Forest; Genentech; Pfizer; Sanofi-Aventis; Takeda FX The education programme referenced in this paper was supported entirely through participant tuition. The MGH-PA has been co-supported through participant tuition and Independent Medical Education (IME) grants from pharmaceutical companies. Drs Fromson, Gorrindo and Birnbaum received honoraria from Reed Medical Education (a for-profit company working as a logistics collaborator for the MGH-PA) for other educational programmes that are supported by IME grants from pharmaceutical companies. Commercial entities supporting the MGH-PA in 2009 are as follows: Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Forest, Genentech, Pfizer, Sanofi-Aventis and Takeda. NR 14 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD MAY PY 2012 VL 6 IS 2 BP 195 EP 200 DI 10.1111/j.1751-7893.2011.00332.x PG 6 WC Psychiatry SC Psychiatry GA 927TT UT WOS:000302933700012 PM 22225592 ER PT J AU van Eeghen, AM Black, ME Pulsifer, MB Kwiatkowski, DJ Thiele, EA AF van Eeghen, Agnies M. Black, Margaux E. Pulsifer, Margaret B. Kwiatkowski, David J. Thiele, Elizabeth A. TI Genotype and cognitive phenotype of patients with tuberous sclerosis complex SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE tuberous sclerosis; cognition; epilepsy; phenotype ID MISSENSE MUTATIONS; MENTAL-RETARDATION; HAMARTIN COMPLEX; CORTICAL TUBERS; TSC2; GENE; IDENTIFICATION; IMPAIRMENT; SEVERITY; SEIZURES AB Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder, which affects 1 in 6000 people. About half of these patients are affected by mental retardation, which has been associated with TSC2 mutations, epilepsy severity and tuber burden. The bimodal intelligence distribution in TSC populations suggests the existence of subgroups with distinct pathophysiologies, which remain to be identified. Furthermore, it is unknown if heterozygous germline mutations in TSC2 can produce the neurocognitive phenotype of TSC independent of epilepsy and tubers. Genotype-phenotype correlations may help to determine risk profiles and select patients for targeted treatments. A retrospective chart review was performed, including a large cohort of 137 TSC patients who received intelligence assessment and genetic mutation analysis. The distribution of intellectual outcomes was investigated for selected genotypes. Genotype-neurocognitive phenotype correlations were performed and associations between specific germline mutations and intellectual outcomes were compared. Results showed that TSC1 mutations in the tuberin interaction domain were significantly associated with lower intellectual outcomes (P<0.03), which was also the case for TSC2 protein-truncating and hamartin interaction domain mutations (both P<0.05). TSC2 missense mutations and small in-frame deletions were significantly associated with higher IQ/DQs (P<0.05). Effects related to the mutation location within the TSC2 gene were found. These findings suggest that TSC2 protein-truncating mutations and small in-frame mutations are associated with distinctly different intelligence profiles, providing further evidence that different types and locations of TSC germline mutations may be associated with distinct neurocognitive phenotypes. European Journal of Human Genetics (2012) 20, 510-515; doi:10.1038/ejhg.2011.241; published online 21 December 2011 C1 [van Eeghen, Agnies M.; Black, Margaux E.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, Boston, MA 02114 USA. [van Eeghen, Agnies M.] Erasmus MC, Dept Neurosci, Expertise Ctr Neurodev Disorders, ENCORE, Rotterdam, Netherlands. [Pulsifer, Margaret B.] Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, Boston, MA 02114 USA. [Kwiatkowski, David J.] Brigham & Womens Hosp, Dept Med, Translat Med Div, Boston, MA 02115 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Herscot Center for TSC; NIH/NINDS [1P01NS24279] FX We are very grateful for the helpful suggestions regarding the selection of missense mutation location by Mark Nellist, PhD, and for the graphing assistance by Peter Pulsifer, PhD, and Anna Larson. Statistical analysis was performed with assistance of Brian Healy of the Biostatistics Center of our hospital. This work was supported by the Herscot Center for TSC and NIH/NINDS 1P01NS24279. NR 43 TC 26 Z9 26 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2012 VL 20 IS 5 BP 510 EP 515 DI 10.1038/ejhg.2011.241 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 928VU UT WOS:000303016800015 PM 22189265 ER PT J AU Ozcan, C Rottman, JN Heist, EK Guy, ML Ellinor, PT Singh, J Milan, DJ Danik, SB Barrett, CD Mansour, M Ruskin, JN Mela, T AF Ozcan, Cevher Rottman, Jeffrey N. Heist, E. Kevin Guy, Mary L. Ellinor, Patrick T. Singh, Jagmeet Milan, David J. Danik, Stephan B. Barrett, Conor D. Mansour, Moussa Ruskin, Jeremy N. Mela, Theofanie TI Unpredictable battery depletion of St Jude Atlas II and Atlas plus II HF implantable cardioverter-defibrillators SO HEART RHYTHM LA English DT Article DE Pulse generator; Malfunction; Elective replacement; Defibrillator; Generator longevity; Cardiac resynchronization ID LONGEVITY; PACEMAKER; REPLACEMENTS AB BACKGROUND Predictable progression to battery depletion is necessary for device management in patients with pacemakers or implantable cardioverter-defibrillators, particularly in patients who either are pacemaker dependent or have required implantable cardioverter-defibrillator therapies. OBJECTIVE To determine the incidence and characteristics of unexpected battery depletion in patients implanted with a cardiac resynchronization therapy - defibrillator (CRT-D) device. METHODS All patients with a St Jude Atlas+ HF or Atlas II HF CRT-D device implanted between 2004 and 2007 at the Massachusetts General Hospital and the Nashville VA Medical Center (Vanderbilt University) were studied. All patients with early generator depletion (transition of generator voltage above specified elective replacement indicator [ERI] to end of life [EOL] in less than 90 days) were evaluated further. RESULTS Eight cases (mean age 69.6 +/- 9 years) with abrupt battery depletion were identified among 191 patients (4.2%) implanted with a St Jude Atlas CRT-D device. The longevity of 8 premature depletion devices was 46.4 +/- 10 months (median 45 months). The battery voltage in these 8 devices decreased from a mean of 2.48 +/- 0.03 V (above ERI) to 2.3 +/- 0.08 V (below ERI) over 33.3 +/- 23 days (range 1-59 days; median 38.5 days). One device reached EOL status within 1 day of having battery voltage above ERI and another device within 12 days. CONCLUSION The incidence of abrupt battery depletion was 4.2% in patients implanted with a St Jude Atlas CRT-D device. No common mechanism has been identified for this failure. Close monitoring of battery voltage and timely generator replacement are required in patients with these devices. C1 [Ozcan, Cevher; Heist, E. Kevin; Guy, Mary L.; Ellinor, Patrick T.; Singh, Jagmeet; Milan, David J.; Danik, Stephan B.; Barrett, Conor D.; Mansour, Moussa; Ruskin, Jeremy N.; Mela, Theofanie] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Rottman, Jeffrey N.] Nashville VA Med Ctr, Div Cardiovasc Med, Nashville, TN USA. [Rottman, Jeffrey N.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. RP Mela, T (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM tmela@partners.org NR 13 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD MAY PY 2012 VL 9 IS 5 BP 717 EP 720 DI 10.1016/j.hrthm.2011.12.009 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 928TO UT WOS:000303008400011 PM 22172318 ER PT J AU French, SL Floyd, M Wilkins, S Osato, S AF French, Samantha L. Floyd, Mark Wilkins, Stacy Osato, Sheryl TI The Fear of Alzheimer's Disease Scale: a new measure designed to assess anticipatory dementia in older adults SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE anticipatory dementia; fear of developing Alzheimer's disease; Alzheimer's disease threat; anxiety; older adults ID TRAIT ANXIETY INVENTORY; SUBJECTIVE FORGETFULNESS; 1ST-DEGREE RELATIVES; PERSONAL-EXPERIENCE; HELP-SEEKING; POPULATION; PREVALENCE AB Background: As the prevalence of Alzheimer's disease (AD) is rapidly increasing, apprehension about developing the degenerative disease (anticipatory dementia or fear of developing AD) has become a topic of interest. However, most studies of anticipatory dementia have utilized brief, nonvalidated measures to explore older adults' apprehension. As such, there is a significant need for a psychometrically sound instrument to measure this fear. Methods: The current study utilized 101 older adults ages 65 to 91 to develop and validate an important new scale, the Fear of Alzheimer's Disease Scale (FADS). Construct validity of the FADS was assessed with the State-Trait Anxiety Inventory-Form Y (STAI-Y). Results: Analyses revealed a three-factor model for the FADS (i.e., General Fear, Physical Symptoms, and Catastrophic Attitude) and an alpha of 0.94 for the entire measure, indicating good internal consistency. The FADS demonstrated good construct validity, as it was significantly correlated with both the state and trait subscales of the STAI-Y, with the trait subscale yielding the highest correlation. Conclusion: The FADS is a reliable and valid instrument and is the first of its kind available to directly address anticipatory dementia among a general population of older adults. Copyright (C) 2011 John Wiley& Sons, Ltd. C1 [French, Samantha L.] Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. [French, Samantha L.; Wilkins, Stacy; Osato, Sheryl] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Floyd, Mark] VA N Texas Healthcare Syst, Bonham, TX USA. [Wilkins, Stacy; Osato, Sheryl] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [French, Samantha L.] VA Loma Linda Healthcare Syst, Loma Linda, CA USA. RP French, SL (reprint author), Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. EM Samantha.French@va.gov NR 35 TC 8 Z9 8 U1 0 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD MAY PY 2012 VL 27 IS 5 BP 521 EP 528 DI 10.1002/gps.2747 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 926XL UT WOS:000302865200011 PM 21721044 ER PT J AU Margalit, DN Kasperzyk, JL Martin, NE Sesso, HD Gaziano, JM Ma, J Stampfer, MJ Mucci, LA AF Margalit, Danielle N. Kasperzyk, Julie L. Martin, Neil E. Sesso, Howard D. Gaziano, John Michael Ma, Jing Stampfer, Meir J. Mucci, Lorelei A. TI Beta-carotene Antioxidant Use During Radiation Therapy and Prostate Cancer Outcome in the Physicians' Health Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Antioxidants; Beta-carotene; Outcomes; Prostate cancer; Vitamins ID RANDOMIZED-TRIAL; CARDIOVASCULAR-DISEASE; LUNG-CANCER; VITAMINS E; CHEMOTHERAPY; HEAD; SUPPLEMENTATION; PREVENTION; NUTRIENTS; MUCOSITIS AB Purpose: The safety of antioxidant supplementation during radiation therapy (RT) for cancer is controversial. Antioxidants could potentially counteract the pro-oxidant effects of RT and compromise therapeutic efficacy. We performed a prospective study nested within the Physicians' Health Study (PHS) randomized trial to determine if supplemental antioxidant use during RT for prostate cancer is associated with an increased risk of prostate cancer death or metastases. Methods and Materials: PHS participants (383) received RT for prostate cancer while randomized to receive beta-carotene (50 mg on alternate days) or placebo. The primary endpoint was time from RT to lethal prostate cancer, defined as prostate cancer death or bone metastases. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test to compare groups. Cox proportional hazards regression was used to estimate the effect of beta-carotene compared with that of placebo during RT. Results: With a median follow-up of 10.5 years, there was no significant difference between risk of lethal prostate cancer with the use of beta-carotene during RT compared with that of placebo (hazard ratio = 0.72; 95% confidence interval [CI], 0.42-1.24; p = 0.24). After we adjusted for age at RT, prostate-specific antigen serum level, Gleason score, and clinical stage, the difference remained nonsignificant. The 10-year freedom from lethal prostate cancer was 92% (95% CI, 87-95%) in the beta-carotene group and 89% (95% CI, 84-93%) in the placebo group. Conclusion: The use of supplemental antioxidant beta-carotene during RT was not associated with an increased risk of prostate cancer death or metastases. This study suggests a lack of harm from supplemental beta-carotene during RT for prostate cancer. (C) 2012 Elsevier Inc. C1 [Margalit, Danielle N.; Martin, Neil E.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Margalit, Danielle N.] Harvard Univ, Radiat Oncol Program, Boston, MA 02115 USA. [Kasperzyk, Julie L.; Ma, Jing; Stampfer, Meir J.; Mucci, Lorelei A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Channing Lab, Dept Med, Boston, MA 02215 USA. [Gaziano, John Michael] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Aging, Boston, MA 02215 USA. [Sesso, Howard D.; Gaziano, John Michael] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. [Gaziano, John Michael] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Margalit, Danielle N.; Kasperzyk, Julie L.; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Margalit, DN (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM dmargalit@lroc.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU National Institutes of Health [T32 CA09001]; American Institute for Cancer Research; Physicians' Health Study [CA-34944, CA-40360, CA-097193, HL-26490, HL-34595]; Prostate Cancer Foundation; American Heart Association; American Cancer Society; California Strawberry Commission; Tomato Products Wellness Council; Roche Vitamins, Inc.(DSM Pharmaceuticals); Cambridge Theranostics, Ltd. FX This work was supported by National Institutes of Health (T32 CA09001 to D.N.M., J.L.K., and principal investigator M.J.S.), American Institute for Cancer Research (to J.L.K.), grants CA-34944, CA-40360, CA-097193, HL-26490, and HL-34595 from the Physicians' Health Study, and the Prostate Cancer Foundation (to L.A.M.).; During the previous 5 years, H.D.S. has received investigator-initiated research funding as principal investigator from the not-for-profit entities National Institutes of Health, American Heart Association, American Cancer Society, California Strawberry Commission, and Tomato Products Wellness Council and from the for-profit entities Roche Vitamins, Inc.(DSM Pharmaceuticals) and Cambridge Theranostics, Ltd., and has served as consultant to Iovate Health Sciences USA, Inc. NR 23 TC 10 Z9 11 U1 1 U2 5 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 MAY 1 PY 2012 VL 83 IS 1 BP 28 EP 32 DI 10.1016/j.ijrobp.2011.05.032 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 928OZ UT WOS:000302993900027 PM 22079732 ER PT J AU Alexander, BM Wang, XZ Niemierko, A Weaver, DT Mak, RH Roof, KS Fidias, P Wain, J Choi, NC AF Alexander, Brian M. Wang, Xiao Zhe Niemierko, Andrzej Weaver, David T. Mak, Raymond H. Roof, Kevin S. Fidias, Panagiotis Wain, John Choi, Noah C. TI DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Therapeut Radiol & Oncol (ASTRO) DE Biomarkers; Chemoradiotherapy; DNA repair; Esophageal cancer ID SQUAMOUS-CELL CARCINOMA; POOR-PROGNOSIS; CHEMOTHERAPY; EXPRESSION; CHEMORADIATION; DEFICIENCY; CISPLATIN; BENEFITS; HMLH1 AB Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need confirmation in an independent data set. (C) 2012 Elsevier Inc. C1 [Alexander, Brian M.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Wang, Xiao Zhe; Weaver, David T.] On Q Ity Inc, Waltham, MA USA. [Wang, Xiao Zhe; Weaver, David T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Fidias, Panagiotis] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wain, John] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Roof, Kevin S.] SE Radiat Oncol, Charlotte, NC USA. RP Alexander, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM bmalexander@lroc.harvard.edu NR 21 TC 19 Z9 21 U1 0 U2 3 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 MAY 1 PY 2012 VL 83 IS 1 BP 164 EP 171 DI 10.1016/j.ijrobp.2011.05.033 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 928OZ UT WOS:000302993900046 PM 22000749 ER PT J AU Fox, AM Dosoretz, AP Mauch, PM Chen, YH Fisher, DC LaCasce, AS Freedman, AS Silver, B Ng, AK AF Fox, Amy M. Dosoretz, Arie P. Mauch, Peter M. Chen, Yu-Hui Fisher, David C. LaCasce, Ann S. Freedman, Arnold S. Silver, Barbara Ng, Andrea K. TI Predictive Factors for Radiation Pneumonitis in Hodgkin Lymphoma Patients Receiving Combined-Modality Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Hodgkin lymphoma; Radiation pneumonitis; Mean lung dose; Pulmonary toxicity ID INTENSITY-MODULATED RADIOTHERAPY; HIGH-DOSE CHEMOTHERAPY; BONE-MARROW-TRANSPLANTATION; INVOLVED-NODE RADIOTHERAPY; STEM-CELL TRANSPLANTATION; MEDIASTINAL IRRADIATION; PULMONARY-FUNCTION; ABVD CHEMOTHERAPY; VIRTUAL VOLUMES; DISEASE AB Purpose: This study sought to quantify the risk of radiation pneumonitis (RP) in Hodgkin lymphoma (HL) patients receiving mediastinal radiation therapy (RT) and to identify predictive factors for RP. Methods and Materials: We identified 75 patients with newly diagnosed HL treated with mediastinal RT and 17 patients with relapsed/refractory HL treated with mediastinal RT before or after transplant. Lung dose-volumetric parameters including mean lung dose and percentage of lungs receiving 20 Gy were calculated. Factors associated with RP were explored by use of the Fisher exact test. Results: RP developed in 7 patients (10%) who received mediastinal RT as part of initial therapy (Radiation Therapy Oncology Group Grade 1 in 6 cases). A mean lung dose of 13.5 Gy or greater (p = 0.04) and percentage of lungs receiving 20 Gy of 33.5% or greater (p = 0.009) significantly predicted for RP. RP developed in 6 patients (35%) with relapsed/refractory HL treated with peri-transplant mediastinal RT (Grade 3 in 4 cases). Pre-transplant mediastinal RT, compared with post-transplant mediastinal RT, significantly predicted for Grade 3 RP (57% vs. 0%, p = 0.015). Conclusions: We identified threshold lung metrics predicting for RP in HL patients receiving mediastinal RT as part of initial therapy, with the majority of cases being of mild severity. The risk of RP is significantly higher with peri-transplant mediastinal RT, especially among those who receive pre-transplant RT. (C) 2012 Elsevier Inc. C1 [Fox, Amy M.; Dosoretz, Arie P.; Mauch, Peter M.; Silver, Barbara; Ng, Andrea K.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Fisher, David C.; LaCasce, Ann S.; Freedman, Arnold S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fox, Amy M.] 21st Century Oncol, Ft Myers, FL USA. [Dosoretz, Arie P.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu NR 30 TC 11 Z9 13 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 MAY 1 PY 2012 VL 83 IS 1 BP 277 EP 283 DI 10.1016/j.ijrobp.2011.05.078 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 928OZ UT WOS:000302993900061 PM 22019238 ER PT J AU Seco, J Panahandeh, HR Westover, K Adams, J Willers, H AF Seco, Joao Panahandeh, Hamid Reza Westover, Kenneth Adams, Judith Willers, Henning TI Treatment of Non-Small Cell Lung Cancer Patients With Proton Beam-Based Stereotactic Body Radiotherapy: Dosimetric Comparison With Photon Plans Highlights Importance of Range Uncertainty SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE SBRT; Proton; Photon; NSCLC ID INTERNATIONAL STAGING SYSTEM; VOLUME HISTOGRAM ANALYSIS; PROSPECTIVE PHASE-II; RADIATION-THERAPY; CLINICAL-OUTCOMES; CARCINOMA; TOXICITY; VERIFICATION; PNEUMONITIS; RESECTION AB Purpose: Proton beam radiotherapy has been proposed for use in stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung cancer. In the present study, we sought to analyze how the range uncertainties for protons might affect its therapeutic utility for SBRT. Methods and Materials: Ten patients with early-stage non-small-cell lung cancer received SBRT with two to three proton beams. The patients underwent repeat planning for photon SBRT, and the dose distributions to the normal and tumor tissues were compared with the proton plans. The dosimetric comparisons were performed within an operational definition of high-and low-dose regions representing volumes receiving >50% and <50% of the prescription dose, respectively. Results: In high-dose regions, the average volume receiving >= 95% of the prescription dose was larger for proton than for photon SBRT (i.e., 46.5 cm(3) vs. 33.5 cm(3); p = . 009, respectively). The corresponding conformity indexes were 2.46 and 1.56. For tumors in close proximity to the chest wall, the chest wall volume receiving >= 30 Gy was 7 cm(3) larger for protons than for photons (p =. 06). In low-dose regions, the lung volume receiving >= 5 Gy and maximum esophagus dose were smaller for protons than for photons (p = .019 and p < .001, respectively). Conclusions: Protons generate larger high-dose regions than photons because of range uncertainties. This can result in nearby healthy organs (e.g., chest wall) receiving close to the prescription dose, at least when two to three beams are used, such as in our study. Therefore, future research should explore the benefit of using more than three beams to reduce the dose to nearby organs. Additionally, clinical subgroups should be identified that will benefit from proton SBRT. (C) 2012 Elsevier Inc. C1 [Seco, Joao; Panahandeh, Hamid Reza; Westover, Kenneth; Adams, Judith; Willers, Henning] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Seco, Joao; Panahandeh, Hamid Reza; Westover, Kenneth; Adams, Judith; Willers, Henning] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Westover, Kenneth] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. RP Seco, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM jseco@partners.org RI Seco, Joao/J-4451-2012 NR 43 TC 24 Z9 24 U1 0 U2 4 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 MAY 1 PY 2012 VL 83 IS 1 BP 354 EP 361 DI 10.1016/j.ijrobp.2011.05.062 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 928OZ UT WOS:000302993900072 PM 21985941 ER PT J AU Tang, SK Both, S Bentefour, H Paly, JJ Tochner, Z Efstathiou, J Lu, HM AF Tang, Shikui Both, Stefan Bentefour, Hassan Paly, Jonathan J. Tochner, Zelig Efstathiou, Jason Lu, Hsiao-Ming TI Improvement of Prostate Treatment by Anterior Proton Fields SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Prostate cancer; Comparative treatment planning; Proton therapy; Anterior field ID VIVO RANGE VERIFICATION; RADIATION-THERAPY; DOSE-ESCALATION; CANCER; RADIOTHERAPY; RISK AB Purpose: We performed a treatment planning study to demonstrate the potential dosimetric benefits of anterior-oriented fields for prostate irradiation by proton beam. A novel in vivo beam range control method shows millimeter accuracy, suggesting that such fields could be safely used to spare the rectum given the sharp distal penumbra of protons. Methods and Materials: Ten prostate patients treated with water-filled endorectal balloon were selected. Bilateral fields were planned following the conventional treatment protocol. Three anterior-oriented fields (0, +30, -30 degrees) were planned, with the range compensators manually adjusted to improve rectal sparing. Dose distributions to the clinical target volume, rectum, anterior rectal wall (ARW), bladder, bladder wall (BW), and femoral heads were compared for: A) equally weighted bilateral fields, B) a single straight anterior field, and C) two equally weighted anterior-oblique fields. Results: The anterior-oriented fields required much less beam energy, similar to 10 cm water equivalent path length less than lateral fields. For ARW, the V-95% for Plans A, B, and C were 39%, 8%, and 6%, respectively; the corresponding V-80% were 59%, 27%, and 26%, respectively (p = 0.002 when Plan A was compared with B or C). Plan B irradiated a larger volume of BW than did Plan A by 3% at V-95%, 11% at V-80%, and 16% at V-50% (p = 0.002), whereas Plan C differs little from Plan A for BW at these dose levels. The femoral heads received similar to 40% of the prescription dose in Plan A, but negligible dose in Plans B and C. Conclusions: Compared to lateral fields, anterior-oriented fields can significantly reduce dose to the ARW, particularly at high dose levels. These fields alone, or in combination with lateral fields, allow for the possibility of either reducing treatment toxicity at current prescription doses or further dose escalation in the treatment of prostate cancer. (C) 2012 Elsevier Inc. C1 [Tang, Shikui; Paly, Jonathan J.; Efstathiou, Jason; Lu, Hsiao-Ming] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Both, Stefan; Tochner, Zelig] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Both, Stefan; Tochner, Zelig] Ion Beam Applicat, Louvain, Belgium. RP Lu, HM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM hmlu@partners.org RI Tang, Shikui/D-9798-2012 FU federal share of program income [C06 CA059267] FX Supported by the federal share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 19 TC 22 Z9 22 U1 0 U2 3 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 MAY 1 PY 2012 VL 83 IS 1 BP 408 EP 418 DI 10.1016/j.ijrobp.2011.06.1974 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 928OZ UT WOS:000302993900079 PM 22133626 ER PT J AU Hallman, JL Mori, S Sharp, GC Lu, HM Hong, TS Chen, GTY AF Hallman, Joshua L. Mori, Shinichiro Sharp, Gregory C. Lu, Hsiao-Ming Hong, Theodore S. Chen, George T. Y. TI A Four-Dimensional Computed Tomography Analysis of Multiorgan Abdominal Motion SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Abdominal organ motion; Liver; Pancreas; Four-dimensional computed tomography; Deformable registration ID DOSE DISTRIBUTIONS; ORGAN MOTION; TUMOR MOTION; LUNG-CANCER; CT SCANS; RADIOTHERAPY; MOVEMENT; IMPACT AB Purpose: To characterize and quantify multiorgan respiration-induced motion in the abdomen in liver and pancreatic cancer patients. Methods and Materials: Four-dimensional computed tomography scans were acquired for 18 patients treated for abdominal tumors. Contours of multiple abdominal organs were drawn by the radiation oncologist at one respiratory phase; these contours were propagated to other respiratory phases by deformable registration. Three-dimensional organ models were generated from the resulting contours at each phase. Motions of the bounding box and center of mass were extracted and analyzed for the clinical target volume and organs at risk. Results: On average, the center of mass motion for liver clinical target volumes was 9.7 mm (SD 5 mm) in the superior-inferior direction, with a range of 3 to 18 mm; for pancreatic tumors, the average was 5 mm (SD 1 mm) m with a range of 3 to 7 mm. Abdominal organs move in unison, but with varying amplitudes. Gating near exhale (T40-T60) reduces the range of motion by a factor of similar to 10. Conclusion: We have used deformable registration to calculate the trajectories of abdominal organs in four dimensions, based on center of mass and bounding box motion metrics. Our results are compared with previously reported studies. Possible reasons for differences are discussed. (C) 2012 Elsevier Inc. C1 [Hallman, Joshua L.; Sharp, Gregory C.; Lu, Hsiao-Ming; Hong, Theodore S.; Chen, George T. Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hallman, Joshua L.; Sharp, Gregory C.; Lu, Hsiao-Ming; Hong, Theodore S.; Chen, George T. Y.] Harvard Univ, Sch Med, Boston, MA USA. [Mori, Shinichiro] Natl Inst Radiol Sci, Chiba 260, Japan. RP Chen, GTY (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM gchen@partners.org OI Mori, Shinichiro/0000-0002-0412-4399 FU National Cancer Institute [P01CA021239] FX Supported by Award Number P01CA021239 from the National Cancer Institute. NR 19 TC 21 Z9 22 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2012 VL 83 IS 1 BP 435 EP 441 DI 10.1016/j.ijrobp.2011.06.1970 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 928OZ UT WOS:000302993900082 PM 22197238 ER PT J AU Shah, A Efstathiou, JA Paly, JJ Halpern, SD Bruner, DW Christodouleas, JP Coen, JJ Deville, C Vapiwala, N Shipley, WU Zietman, AL Hahn, SM Bekelman, JE AF Shah, Anand Efstathiou, Jason A. Paly, Jonathan J. Halpern, Scott D. Bruner, Deborah W. Christodouleas, John P. Coen, John J. Deville, Curtiland, Jr. Vapiwala, Neha Shipley, William U. Zietman, Anthony L. Hahn, Stephen M. Bekelman, Justin E. TI Prospective Preference Assessment of Patients' Willingness to Participate in a Randomized Controlled Trial of Intensity-Modulated Radiotherapy Versus Proton Therapy for Localized Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Prostate cancer; Intensity-modulated radiotherapy; Proton beam therapy; Randomized controlled trial ID RADICAL PROSTATECTOMY; INTERVENTION; DESIGN AB Purpose: To investigate patients' willingness to participate (WTP) in a randomized controlled trial (RCT) comparing intensity-modulated radiotherapy (IMRT) with proton beam therapy (PBT) for prostate cancer (PCa). Methods and Materials: We undertook a qualitative research study in which we prospectively enrolled patients with clinically localized PCa. We used purposive sampling to ensure a diverse sample based on age, race, travel distance, and physician. Patients participated in a semi-structured interview in which they reviewed a description of a hypothetical RCT, were asked open-ended and focused follow-up questions regarding their motivations for and concerns about enrollment, and completed a questionnaire assessing characteristics such as demographics and prior knowledge of IMRT or PBT. Patients' stated WTP was assessed using a 6-point Likert scale. Results: Forty-six eligible patients (33 white, 13 black) were enrolled from the practices of eight physicians. We identified 21 factors that impacted patients' WTP, which largely centered on five major themes: altruism/desire to compare treatments, randomization, deference to physician opinion, financial incentives, and time demands/scheduling. Most patients (27 of 46, 59%) stated they would either "definitely" or "probably" participate. Seventeen percent (8 of 46) stated they would "definitely not" or "probably not" enroll, most of whom (6 of 8) preferred PBT before their physician visit. Conclusions: A substantial proportion of patients indicated high WTP in a RCT comparing IMRT and PBT for PCa. (C) 2012 Elsevier Inc. C1 [Shah, Anand; Christodouleas, John P.; Deville, Curtiland, Jr.; Vapiwala, Neha; Hahn, Stephen M.; Bekelman, Justin E.] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. [Halpern, Scott D.; Bekelman, Justin E.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Efstathiou, Jason A.; Paly, Jonathan J.; Coen, John J.; Shipley, William U.; Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bruner, Deborah W.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. RP Bekelman, JE (reprint author), Hosp Univ Penn, Dept Radiat Oncol, PCAM, 3400 Civ Ctr Blvd,TRC 4 W, Philadelphia, PA 19104 USA. EM bekelman@uphs.upenn.edu RI Deville, Curtiland/B-2819-2013 OI Deville, Curtiland/0000-0003-4846-6486 FU University of Pennsylvania Department of Radiation Oncology FX Supported by a health services research fellowship from the University of Pennsylvania Department of Radiation Oncology (A.S.). NR 19 TC 14 Z9 14 U1 0 U2 11 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 MAY 1 PY 2012 VL 83 IS 1 BP E13 EP E19 DI 10.1016/j.ijrobp.2011.11.072 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 928OZ UT WOS:000302993900002 PM 22381899 ER PT J AU Qing, H Ardeshirpour, L Pajevic, PD Dusevich, V Jahn, K Kato, S Wysolmerski, J Bonewald, LF AF Qing, Hai Ardeshirpour, Laleh Pajevic, Paola Divieti Dusevich, Vladimir Jaehn, Katharina Kato, Shigeaki Wysolmerski, John Bonewald, Lynda F. TI Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE PARATHYROID; DISORDERS OF CALCIUM; PHOSPHATE METABOLISM; PTH; PTHrP; HORMONES; RECEPTORS; BONE HISTOMORPHOMETRY; BONE QUANTITATION ID BONE LOSS; IN-VITRO; PARATHYROID-HORMONE; PTH/PTHRP RECEPTOR; TARGETED ABLATION; GAP-JUNCTIONS; OSTEOLYSIS; EXPRESSION; CALCIUM; METABOLISM AB Osteoclasts are thought to be solely responsible for the removal of bone matrix. However, we show here that osteocytes can also remove bone matrix by reversibly remodeling their perilacunar/canalicular matrix during the reproductive cycle. In contrast, no osteocytic remodeling was observed with experimental unloading despite similar degrees of bone loss. Gene array analysis of osteocytes from lactating animals revealed an elevation of genes known to be utilized by osteoclasts to remove bone, including tartrate-resistant acid phosphatase (TRAP) and cathepsin K, that returned to virgin levels upon weaning. Infusion of parathyroid hormonerelated peptide (PTHrP), known to be elevated during lactation, induced TRAP activity and cathepsin K expression in osteocytes concurrent with osteocytic remodeling. Conversely, animals lacking the parathyroid hormone type 1 receptor (PTHR1) in osteocytes failed to express TRAP or cathepsin K or to remodel their osteocyte perilacunar matrix during lactation. These studies show that osteocytes remove mineralized matrix through molecular mechanisms similar to those utilized by osteoclasts. (c) 2012 American Society for Bone and Mineral Research. C1 [Qing, Hai; Dusevich, Vladimir; Jaehn, Katharina; Bonewald, Lynda F.] Univ Missouri, Sch Dent, Kansas City, MO 64108 USA. [Ardeshirpour, Laleh] Yale Univ, Sch Med, Dept Pediat, Sect Pediat Endocrinol, New Haven, CT 06510 USA. [Pajevic, Paola Divieti] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. [Kato, Shigeaki] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan. [Wysolmerski, John] Yale Univ, Sch Med, Dept Internal Med, Sect Endocrinol & Metab, New Haven, CT 06510 USA. RP Bonewald, LF (reprint author), Univ Missouri, Sch Dent, 650 E 25th, Kansas City, MO 64108 USA. EM bonewaldl@umkc.edu RI qing, hai/A-8948-2013; OI Jahn, Katharina/0000-0002-9338-831X FU NIH/NIAMS [PO1 AR046798]; NIH/NIDDK [DK079161, R01 DK073941, K08 DK081731]; NIH/NCI [CA153702] FX We acknowledge Xiaoxiang Ma and Mark Dallas for quantitation of osteocyte lacunae or canalicular width, Carrie Zhao for assistance with the animal husbandry, and Kevin J. Barry for technical support. This work was supported by NIH/NIAMS grant PO1 AR046798 (to LFB), NIH/NIDDK grant DK079161 (to PDP) NIH/NIDDK grant R01 DK073941 (to JW), and NIH/NCI grant CA153702 (to JW), and NIH/NIDDK grant K08 DK081731 (to LA). NR 41 TC 116 Z9 117 U1 0 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 2012 VL 27 IS 5 BP 1018 EP 1029 DI 10.1002/jbmr.1567 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 927VW UT WOS:000302939400007 PM 22308018 ER PT J AU Teles, RP Teles, FRF Loesche, WJ Listgarten, M Fine, D Lindhe, J Malament, K Haffajee, AD AF Teles, R. P. Teles, F. R. F. Loesche, W. J. Listgarten, M. Fine, D. Lindhe, J. Malament, K. Haffajee, A. D. TI Rediscovering Sig Socransky, the Genius and His Legacy SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE bacteria; microbiology; periodontitis; periodontal diseases; microbial complexes; biofilms ID PERIODONTAL DISEASE; ORGANISMS; BACTERIA AB Some individuals make contributions so vital to their field of knowledge that their names become almost synonymous with that field. This is the case of Sig Socransky and the field of periodontal microbiology. Sig Socransky, or simply Sig, was born in Toronto, Canada and received his DDS degree from the University of Toronto in 1957. He studied microbiology and periodontology at Harvard, receiving a certificate in 1961. That same year he was recruited to work as a Research Associate at the Forsyth Dental Center. In 1968, he was nominated Senior Member of the Staff and Head of the Department of Periodontology. During his 50-year career at Forsyth, Sig published over 300 manuscripts, keeping an average of 7 publications per year. His work had an indelible impact in the fields of periodontology and oral microbiology. All these accomplishments pale in comparison with the impact that Sig had on a personal level. We have collected testimonials from some of his former students, closest collaborators, and friends in an attempt to give readers an insight into Sig's personality. We hope we can offer those who knew him through his work a glimpse of how it felt to interact with this remarkable individual. C1 [Teles, R. P.; Teles, F. R. F.; Haffajee, A. D.] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA. [Loesche, W. J.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Div Prosthodont, Ann Arbor, MI 48109 USA. [Listgarten, M.] Univ Calif San Francisco, Dept Orofacial Sci, San Francisco, CA 94143 USA. [Fine, D.] Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Oral Biol, Newark, NJ 07103 USA. [Lindhe, J.] Gothenburg Univ, Gothenburg, Sweden. [Malament, K.] Tufts Univ, Sch Dent Med, Dept Prosthodont, Boston, MA 02111 USA. RP Teles, RP (reprint author), Forsyth Inst, Dept Periodontol, 245 1st St, Cambridge, MA 02142 USA. EM rteles@forsyth.org NR 10 TC 1 Z9 1 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 2012 VL 91 IS 5 BP 433 EP 439 DI 10.1177/0022034512443689 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 927OB UT WOS:000302916300001 PM 22442053 ER PT J AU Freedland, SJ Walter, LC AF Freedland, Stephen J. Walter, Louise C. TI 80 is the new 60: Implications of Irrational Exuberance Regarding Longevity on Prostate Cancer Treatment Decisions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Freedland, Stephen J.] Duke Univ, Surg Sect, Durham VA Med Ctr, Durham, NC 27706 USA. [Freedland, Stephen J.] Duke Univ, Dept Urol Surg, Duke Prostate Ctr, Duke Canc Inst, Durham, NC 27706 USA. [Freedland, Stephen J.] Duke Univ, Dept Pathol, Duke Prostate Ctr, Duke Canc Inst, Durham, NC 27706 USA. [Walter, Louise C.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Freedland, SJ (reprint author), Duke Univ, Surg Sect, Durham VA Med Ctr, Durham, NC 27706 USA. EM steve.freedland@duke.edu FU NCI NIH HHS [R01 CA134425] NR 6 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2012 VL 27 IS 5 BP 485 EP 486 DI 10.1007/s11606-012-2006-8 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 926YM UT WOS:000302869300002 PM 22328015 ER PT J AU Chamie, K Daskivich, TJ Kwan, L Labo, J Dash, A Greenfield, S Litwin, MS AF Chamie, Karim Daskivich, Timothy J. Kwan, Lorna Labo, Jessica Dash, Atreya Greenfield, Sheldon Litwin, Mark S. TI Comorbidities, Treatment and Ensuing Survival in Men with Prostate Cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE prostatic neoplasms; comorbidity; outcome assessment; survival; treatment mismatch ID PROPORTIONAL HAZARDS MODEL; RADICAL PROSTATECTOMY; INITIAL TREATMENT; OUTCOMES; RADIOTHERAPY; STATISTICS; VALIDATION; RADIATION; THERAPY; TRENDS AB Comorbidity is poorly integrated into prostate cancer decision making. We sought to characterize treatment type and subsequent survival for men with no more than a single comorbid condition. We conducted a retrospective study of 1,031 veterans with non-metastatic prostate cancer diagnosed in 1997-2004 at the Greater Los Angeles and Long Beach Veterans Affairs Medical Centers and followed until 2010. We used multivariate analyses to determine probabilities and relative risks of undergoing treatment for each health state and competing-risks regression analyses to model non-prostate cancer mortality. Compared with subjects without any comorbid conditions, only men with moderate-severe chronic obstructive pulmonary disease were less likely to receive definitive treatment for their prostate cancer (RR 0.74; 95% CI 0.44-0.99). Men with all other individual comorbidities were equally likely as men without comorbidity to receive definitive treatment. Compared with men without any comorbidities, a higher hazard rate for non-prostate cancer mortality was identified among men with diabetes without end-organ damage (HR 2.32; 95% CI 1.32-4.08), peripheral vascular disease (HR 2.77; 95% CI 1.14-6.73), moderate-severe chronic obstructive pulmonary disease (HR 5.46; 95% CI 2.68-11.12), diabetes with end-organ damage (HR 4.27; 95% CI 1.64-11.10), those in need of a mobility device (HR 3.29; 95% CI 1.87-5.80), and men with history of alcoholism (HR 1.77; 95% CI 1.07-2.93). Men with comorbid conditions and health states that portend poor prognoses are nonetheless aggressively treated for their prostate cancer. Advancing age modulates this effect. C1 [Chamie, Karim; Daskivich, Timothy J.; Labo, Jessica; Litwin, Mark S.] Univ Calif Los Angeles, Dept Urol, Hlth Serv Res Grp, Los Angeles, CA 90024 USA. [Chamie, Karim; Kwan, Lorna; Litwin, Mark S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Daskivich, Timothy J.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dash, Atreya] Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. [Dash, Atreya] Univ Calif Irvine, Dept Urol, Irvine, CA USA. [Greenfield, Sheldon] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. [Greenfield, Sheldon] Univ Calif Irvine, Hlth Policy Res Inst, Irvine, CA USA. [Litwin, Mark S.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Chamie, K (reprint author), Univ Calif Los Angeles, Dept Urol, Hlth Serv Res Grp, 924 Westwood Blvd,Suite 1000, Los Angeles, CA 90024 USA. EM kchamie@mednet.ucla.edu FU American Cancer Society [117496-PF-09-147-01-CPHPS]; Ruth L. Kirschstein National Research Service Award Extramural [1 F32 CA144461-01]; Jonsson Comprehensive Cancer Center; National Institute of Diabetes and Digestive and Kidney Diseases [N01-DK-1-2460] FX This work was supported by the American Cancer Society (117496-PF-09-147-01-CPHPS (Principal Investigator: KC)); Ruth L. Kirschstein National Research Service Award Extramural (1 F32 CA144461-01 (Principal Investigator: KC)); Jonsson Comprehensive Cancer Center Seed Grant (Principal Investigator: MSL)); and National Institute of Diabetes and Digestive and Kidney Diseases (N01-DK-1-2460 (Principal investigator: M.S.L.)) NR 20 TC 9 Z9 9 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2012 VL 27 IS 5 BP 492 EP 499 DI 10.1007/s11606-011-1869-4 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 926YM UT WOS:000302869300006 PM 21935751 ER PT J AU Brawarsky, P Neville, BA Fitzmaurice, GM Hassett, MJ Haas, JS AF Brawarsky, Phyllis Neville, Bridget A. Fitzmaurice, Garrett M. Hassett, Michael J. Haas, Jennifer S. TI Use of Annual Mammography Among Older Women with Ductal Carcinoma In Situ SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE ductal carcinoma in situ (breast); mammography; disparities ID BREAST-CANCER SURVIVORS; SCREENING MAMMOGRAPHY; SURVEILLANCE MAMMOGRAPHY; CONSERVING SURGERY; FOLLOW-UP; RISK; DCIS; DISPARITIES; POPULATION; GUIDELINES AB As ductal carcinoma in situ (DCIS) is a risk factor for invasive breast cancer, ongoing annual mammography is important for cancer control, yet little is known about racial/ethnic and other disparities in use among older women with DCIS. SEER-Medicare data was used to identify women age 65-85 years, diagnosed with DCIS from 1992 to 2005 and treated with surgery, but not bilateral mastectomy. We examined factors associated with receipt of an initial mammogram within 1 year of treatment and subsequent annual mammograms for 3 and 5 years. We examined whether follow-up care, by a primary care physician or cancer specialist, or neighborhood characteristics mediated disparities in mammography use. Overall, 91.3% of women had an initial mammogram. After adjustment, blacks and Hispanics were less likely than whites to receive an initial mammogram (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.55-0.99 and OR 0.65, CI 0.46-0.93, respectively, as were women of lower socioeconomic status (SES), women who had a mastectomy or breast conserving surgery without radiation therapy, and women who did not have a physician visit. Overall rates of annual mammography decreased over time. Disparities by SES, initial treatment type, and physician visit did not diminish over time. Physician visits had a modest effect on reducing initial racial/ethnic disparities. Annual mammography among women age 65 to 85 with DCIS declines as women get further from diagnosis. Interventions should focus on reducing disparities in the use of initial surveillance mammography, and increasing surveillance over time. C1 [Brawarsky, Phyllis; Haas, Jennifer S.] Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 02120 USA. [Neville, Bridget A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fitzmaurice, Garrett M.] McLean Hosp, Lab Psychiat Biostat, Belmont, MA 02178 USA. [Fitzmaurice, Garrett M.] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Hassett, Michael J.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Hassett, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. RP Haas, JS (reprint author), Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, 1620 Tremont St, Boston, MA 02120 USA. EM jhaas@partners.org FU American Cancer Society [RSGT CPHPS-114979] FX This work was supported by a grant from the American Cancer Society (RSGT CPHPS-114979). NR 40 TC 3 Z9 3 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2012 VL 27 IS 5 BP 500 EP 505 DI 10.1007/s11606-011-1918-z PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 926YM UT WOS:000302869300007 PM 22005943 ER PT J AU Ahluwalia, SC Gross, CP Chaudhry, SI Ning, YM Leo-Summers, L Van Ness, PH Fried, TR AF Ahluwalia, Sangeeta C. Gross, Cary P. Chaudhry, Sarwat I. Ning, Yuming M. Leo-Summers, Linda Van Ness, Peter H. Fried, Terri R. TI Impact of Comorbidity on Mortality Among Older Persons with Advanced Heart Failure SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE heart failure; mortality; comorbidity ID DIFFERENTIAL PROGNOSTIC IMPACT; CHRONIC KIDNEY-DISEASE; POPULATION; HOSPITALIZATIONS; ASSOCIATION; PREVALENCE; CANCER AB Care for patients with advanced heart failure (HF) has traditionally focused on managing HF alone; however, little is known about the prevalence and contribution of comorbidity to mortality among this population. We compared the impact of comorbidity on mortality in older adults with HF with high mortality risk and those with lower mortality risk, as defined by presence or absence of a prior hospitalization for HF, respectively. This was a retrospective cohort study (2002-2006) of 18,322 age-matched and gender-matched Medicare beneficiaries. We used the baseline year of 2002 to ascertain HF hospitalization history, in order to identify beneficiaries at either high or low risk of future HF mortality. We calculated the prevalence of 19 comorbidities and overall comorbidity burden, defined as a count of conditions, among both high and low risk beneficiaries, in 2002. Proportional hazards regressions were used to determine the effect of individual comorbidity and comorbidity burden on mortality between 2002 and 2006 among both groups. Most comorbidities were significantly more prevalent among hospitalized versus non-hospitalized beneficiaries; myocardial infarction, atrial fibrillation, kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and hip fracture were more than twice as prevalent in the hospitalized group. Among hospitalized beneficiaries, myocardial infarction, diabetes, COPD, CKD, dementia, depression, hip fracture, stroke, colorectal cancer and lung cancer were each significantly associated with increased hazard of dying (hazard ratios [HRs]: 1.16-1.93), adjusting for age, gender and race. The mortality risk associated with most comorbidities was higher among non-hospitalized beneficiaries (HRs: 1.32-3.78). Comorbidity confers a significantly increased mortality risk even among older adults with an overall high mortality risk due to HF. Clinicians who routinely care for this population should consider the impact of comorbidity on outcomes in their overall management of HF. Such information may also be useful when considering the risks and benefits of aggressive, high-intensity life-prolonging interventions. C1 [Ahluwalia, Sangeeta C.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA 90064 USA. [Gross, Cary P.; Chaudhry, Sarwat I.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Ning, Yuming M.; Leo-Summers, Linda; Van Ness, Peter H.] Yale Univ, Sch Med, Program Aging, New Haven, CT USA. [Van Ness, Peter H.; Fried, Terri R.] Yale Univ, Sch Med, Dept Internal Med, Sect Geriatr, New Haven, CT 06510 USA. [Fried, Terri R.] VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, West Haven, CT USA. RP Ahluwalia, SC (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, 11301 Wilshire Blvd 111-G, Los Angeles, CA 90064 USA. EM sangeeta.ahluwalia@va.gov OI Walton, Kerry/0000-0003-2272-3878 FU National Institute on Aging [T32AG1934, K24 AG028443, K23AG030986]; Office of Academic Affiliation's VA at the VA Greater Los Angeles HSR&D Center of Excellence; Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (NIH/NIA) [2P30AG021342-06] FX Dr. Ahluwalia was supported by a training grant from the National Institute on Aging (T32AG1934) and is currently supported by an Office of Academic Affiliation's VA Associated Health Postdoctoral Fellowship Program at the VA Greater Los Angeles HSR&D Center of Excellence. Dr. Fried is a recipient of a Midcareer Investigator Award in Patient-Oriented Research from the National Institute on Aging (K24 AG028443). Dr. Chaudhry is the recipient of a Paul Beeson/K23 Career Development Award (K23AG030986) from the National Institute on Aging. Supported by the Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (#2P30AG021342-06 NIH/NIA). NR 25 TC 32 Z9 32 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2012 VL 27 IS 5 BP 513 EP 519 DI 10.1007/s11606-011-1930-3 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 926YM UT WOS:000302869300009 PM 22095572 ER PT J AU Sun, VK Cenzer, IS Kao, HL Ahalt, C Williams, BA AF Sun, Vivien K. Cenzer, Irena Stijacic Kao, Helen Ahalt, Cyrus Williams, Brie A. TI How Safe is Your Neighborhood? Perceived Neighborhood Safety and Functional Decline in Older Adults SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE functional decline; disparities; neighborhood safety; elderly ID RISK-FACTORS; ELDERLY-PEOPLE; MENTAL-HEALTH; FEAR; CRIME; MOBILITY; LIFE; PREDICTION; MORTALITY; ASSOCIATION AB Neighborhood characteristics are associated with health and the perception of safety is particularly important to exercise and health among older adults. Little is known about the relationship between perception of neighborhood safety and functional decline in older adults. To determine the relationship between perceived neighborhood safety and functional decline in older adults. Longitudinal, community-based. 18,043 persons, 50 years or older, who participated in the 1998 and 2008 Health and Retirement Study. The primary outcome was 10-year functional decline (new difficulty or dependence in any Activity of Daily Living, new mobility difficulty, and/or death). The primary predictor was perceived neighborhood safety categorized into three groups: "very safe", "moderately safe", and "unsafe." We evaluated the association between perceived neighborhood safety and 10-year functional decline using a modified Poisson regression to generate unadjusted and adjusted relative risks (ARR). At baseline 11,742 (68.0%) participants perceived their neighborhood to be very safe, 4,477 (23.3%) moderately safe, and 1,824 (8.7%) unsafe. Over 10 years, 10,338 (53.9%) participants experienced functional decline, including 6,266 (50.2%) who had perceived their neighborhood to be very safe, 2,839 (61.2%) moderately safe, and 1,233 (63.6%) unsafe, P < 0.001. For the 11,496 (63.3%) of participants who were functionally independent at baseline, perceived neighborhood safety was associated with 10-year functional decline (moderately safe ARR 1.15 95% CI 1.09-1.20; unsafe ARR 1.21 95% CI: 1.03-1.31 compared to very safe group). The relationship between perceived neighborhood safety and 10-year functional decline was not statistically significant for participants who had baseline functional impairment. Asking older adults about their perceived neighborhood safety may provide important information about their risk of future functional decline. These findings also suggest that future studies might focus on assessing whether interventions that promote physical activity while addressing safety concerns help reduce functional decline in older adults. C1 [Cenzer, Irena Stijacic; Kao, Helen; Ahalt, Cyrus; Williams, Brie A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Sun, Vivien K.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Cenzer, Irena Stijacic; Williams, Brie A.] San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco, CA USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Div Geriatr, Box 1265,Suite 380,3333 Calif St, San Francisco, CA 94143 USA. EM brie.williams@ucsf.edu FU National Institute of Aging [K23AG033102]; UCSF Hartford Center of Excellence; Jacob and Valeria Langeloth Foundation; UCSF; American Federation for Aging Research FX Dr. Williams is supported by the National Institute of Aging (K23AG033102), The UCSF Hartford Center of Excellence, The Jacob and Valeria Langeloth Foundation, and the UCSF Program for the Aging Century. Vivien Sun received funding from the National Institute on Aging and the American Federation for Aging Research through the Medical Student Training in Aging Research (MSTAR) Program. These funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Dr. Williams is an employee of the Department of Veterans Affairs. The opinions expressed in this manuscript may not represent those of the VA. NR 42 TC 4 Z9 4 U1 3 U2 25 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 MAY PY 2012 VL 27 IS 5 BP 541 EP 547 DI 10.1007/s11606-011-1943-y PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 926YM UT WOS:000302869300013 PM 22160889 ER PT J AU Lakin, J Baxi, SM Kohlwes, J AF Lakin, Joshua Baxi, Sanjiv M. Kohlwes, Jeff TI Missing the Tree for the Forest: A Case of Secondary Spontaneous Pneumothorax SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE emergency medicine; pulmonary diseases; infectious disease; clinical image C1 [Lakin, Joshua; Baxi, Sanjiv M.] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA. [Kohlwes, Jeff] San Francisco Vet Adm Med Ctr, Dept Internal Med, San Francisco, CA USA. RP Lakin, J (reprint author), Univ Calif San Francisco, Dept Internal Med, 505 Parnassus Ave,Room M-987, San Francisco, CA 94143 USA. EM Joshua.lakin@ucsf.edu NR 3 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2012 VL 27 IS 5 BP 601 EP 602 DI 10.1007/s11606-011-1954-8 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 926YM UT WOS:000302869300022 PM 22215268 ER PT J AU Spassieva, SD Rahmaniyan, M Bielawski, J Clarke, CJ Kraveka, JM Obeid, LM AF Spassieva, Stefka D. Rahmaniyan, Mehrdad Bielawski, Jacek Clarke, Christopher J. Kraveka, Jacqueline M. Obeid, Lina M. TI Cell density-dependent reduction of dihydroceramide desaturase activity in neuroblastoma cells SO JOURNAL OF LIPID RESEARCH LA English DT Article DE sphingolipid; dihydroceramide; ceramide; cell-cycle arrest ID CERAMIDE SYNTHESIS; MASS-SPECTROMETRY; GROWTH ARREST; METABOLISM; SPHINGOSINE-1-PHOSPHATE; SPHINGOLIPIDS; CANCER; IDENTIFICATION; SPHINGOSINE; INVOLVEMENT AB We applied a metabolic approach to investigate the role of sphingolipids in cell density-induced growth arrest in neuroblastoma cells. Our data revealed that sphingolipid metabolism in neuroblastoma cells significantly differs depending on the cells' population context. At high cell density, cells exhibited G0/G1 cell-cycle arrest and reduced ceramide, monohexosylceramide, and sphingomyelin, whereas dihydroceramide was significantly increased. In addition, our metabolic-labeling experiments showed that neuroblastoma cells at high cell density preferentially synthesized very long chain (VLC) sphingolipids and dramatically decreased synthesis of sphingosine-1-phosphate (S1P). Moreover, densely populated neuroblastoma cells showed increased message levels of both anabolic and catabolic enzymes of the sphingolipid pathway. Notably, our metabolic-labeling experiments indicated reduced dihydroceramide desaturase activity at confluence, which was confirmed by direct measurement of dihydroceramide desaturase activity in situ and in vitro. Importantly, we could reduce dihydroceramide desaturase activity in low-density cells by applying conditional media from high-density cells, as well as by adding reducing agents, such as DTT and L-cysteine to the media.jlr In conclusion, our data suggest a role of the sphingolipid pathway, dihydroceramides desaturase in particular, in confluence-induced growth arrest in neuroblastoma cells.-Spassieva, S. D., M. Rahmaniyan, J. Bielawski, C. J. Clarke, J. M. Kraveka, and L. M. Obeid. Cell density-dependent reduction of dihydroceramide desaturase activity in neuroblastoma cells. J. Lipid Res. 2012. 53: 918-928. C1 [Spassieva, Stefka D.; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Rahmaniyan, Mehrdad; Kraveka, Jacqueline M.] Med Univ S Carolina, Div Hematol Oncol, Dept Pediat, Charleston, SC 29425 USA. [Bielawski, Jacek; Clarke, Christopher J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Hosp, Div Gen Internal Med, Charleston, SC 29401 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [AG-016583, P20-RR17677, C06-RR-018823]; Office of Research and Development; Department of Veterans Affairs; Ralph H. Johnson VA Medical Center, Charleston, SC; Rally Foundation for Childhood Cancer Research; Monica Kreber Golf Tournament; Chase After a Cure Foundation; Hyundai Hope on Wheels FX This work was supported by National Institutes of Health Grants AG-016583 (to L.M.O.) and P20-RR17677 (to J.M.K.); by a MERIT Award (to L.M.O.) from the Office of Research and Development, Department of Veterans Affairs, Ralph H. Johnson VA Medical Center, Charleston, SC; and by grants from the Rally Foundation for Childhood Cancer Research, the Monica Kreber Golf Tournament, Chase After a Cure Foundation, and Hyundai Hope on Wheels (to J.M.K.). The MUSC Lipidomics facility was constructed with support from National Institutes of Health Grant C06-RR-018823. The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 41 TC 8 Z9 8 U1 0 U2 1 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 MAY PY 2012 VL 53 IS 5 BP 918 EP 928 DI 10.1194/jlr.M019075 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 925UI UT WOS:000302786800010 PM 22377532 ER PT J AU Manchikanti, L Helm, S Hirsch, JA AF Manchikanti, Laxmaiah Helm, Standiford Hirsch, Joshua A. TI The evolution of the Patient-Centered Outcomes Research Institute SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID INTERVENTIONAL PAIN MANAGEMENT; CLINICAL-PRACTICE GUIDELINES; FALLACIES; POLITICS; FACTS; CARE; ACT C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Helm, Standiford] Pacific Coast Pain Management Ctr, Laguna Hills, CA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept NeuroIntervent Radiol, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 25 TC 27 Z9 27 U1 1 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAY PY 2012 VL 4 IS 3 BP 157 EP 162 DI 10.1136/neurintsurg-2011-010114 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 925SV UT WOS:000302782600013 PM 21990542 ER PT J AU Yoo, AJ Frei, D Tateshima, S Turk, AS Hui, FK Brook, AL Heck, DV Hirsch, JA AF Yoo, Albert J. Frei, Don Tateshima, Satoshi Turk, Aquilla S. Hui, Ferdinand K. Brook, Allan L. Heck, Don V. Hirsch, Joshua A. TI The Penumbra Stroke System: a technical review SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; MERCI TRIAL; INTRAARTERIAL; RECANALIZATION; METAANALYSIS; EXPERIENCE; EFFICACY AB Major ischemic strokes secondary to proximal artery occlusions are responsible for significant morbidity and mortality. Owing to extensive clot burden, these strokes are poorly responsive to intravenous tissue plasminogen activator. The introduction of endovascular therapy, particularly mechanical devices, has resulted in markedly improved recanalization rates of large vessel occlusions. With increasing experience with the Penumbra Stroke System and the 054 reperfusion catheter, there has been further improvement in TIMI 2 and 3 revascularization rates with faster times to vessel opening. The aim of this technical review is to convey various tips and tricks learnt from this experience. C1 [Yoo, Albert J.] Massachusetts Gen Hosp, Dept Intervent & Diagnost Neuroradiol, Boston, MA 02114 USA. [Frei, Don] Radiol Imaging Associates, Dept Intervent Neuroradiol, Englewood, CO USA. [Tateshima, Satoshi] Univ Calif Los Angeles, Med Ctr, Dept Intervent Neuroradiol, Los Angeles, CA 90024 USA. [Turk, Aquilla S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Hui, Ferdinand K.] Cleveland Clin, Cerebrovasc Ctr, Cleveland, OH 44106 USA. [Brook, Allan L.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Heck, Don V.] Forsyth Med Ctr, Dept Radiol, Winston Salem, NC USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Boston, MA 02114 USA. RP Yoo, AJ (reprint author), Massachusetts Gen Hosp, Dept Intervent & Diagnost Neuroradiol, 55 Fruit St,Gray 241, Boston, MA 02114 USA. EM ajyoo@partners.org FU Penumbra Inc FX AJY receives research support from Penumbra Inc for the Core Imaging Lab for the START trial. DF is a consultant and/or serves on the speakers' bureau for Penumbra, Stryker Neurovascular, Genentech and Codman. AST and DVH are consultants for Penumbra Inc. JAH is a shareholder in Intratech. NR 15 TC 16 Z9 16 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAY PY 2012 VL 4 IS 3 BP 199 EP 205 DI 10.1136/neurintsurg-2011-010080 PG 7 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 925SV UT WOS:000302782600025 PM 21990525 ER PT J AU Deipolyi, AR Hirsch, JA Oklu, R AF Deipolyi, Amy R. Hirsch, Joshua A. Oklu, Rahmi TI Bilateral inferior petrosal sinus sampling SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; DEPENDENT CUSHINGS-SYNDROME; ADRENOCORTICOTROPIC HORMONE; DIFFERENTIAL-DIAGNOSIS; DISEASE; ADENOMAS; COMPLICATIONS; POPULATION AB Bilateral inferior petrosal sinus sampling, the gold standard assay in diagnosing pituitary secretion of adrenocorticotropic hormone in Cushing disease, is highly accurate and safe when performed by experienced interventionalists. We review the anatomic and technical considerations essential for safe and reliable practice. C1 [Deipolyi, Amy R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Deipolyi, Amy R.; Hirsch, Joshua A.; Oklu, Rahmi] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Imaging, Div NeuroIntervent Radiol, Boston, MA 02114 USA. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Div Vasc Imaging & Intervent, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA. EM roklu@partners.org OI Deipolyi, Amy/0000-0003-3144-386X FU NIBIB NIH HHS [L30 EB012342] NR 30 TC 5 Z9 5 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAY PY 2012 VL 4 IS 3 BP 215 EP 218 DI 10.1136/neurintsurg-2011-010033 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 925SV UT WOS:000302782600028 PM 21990499 ER PT J AU Vanderboom, TL Arcari, PM Duffy, ME Somarouthu, B Rabinov, JD Yoo, AJ Hirsch, JA AF Vanderboom, Teresa L. Arcari, Patricia M. Duffy, Mary E. Somarouthu, B. Rabinov, James D. Yoo, Albert J. Hirsch, Joshua A. TI Effects of a music intervention on patients undergoing cerebral angiography: a pilot study SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID RANDOMIZED-TRIAL; ANALGESIA; ANXIETY; THERAPY; STRESS AB Purpose To test the effect of a music intervention on procedural anxiety, stress response and medication requirements in participants with a cerebral aneurysm or arteriovenous malformation (AVM) undergoing cerebral angiography. Method and materials A prospective pilot study was conducted using an experimental two group pre-test, post-test design. 48 participants were randomly assigned to a control group (standard care) or experimental group (standard care plus self-selected music via overhead stereo system). The stress response was measured by heart rate (HR) and systolic blood pressure (SBP) at baseline, and during and following the procedure. Anxiety was measured by the State Trait Anxiety Inventory for Adults (STAI) before and after the procedure, and total medications administered periprocedurally were recorded. Results 24 participants in each group were enrolled. R-ANCOVA revealed non-significant findings for HR (F = 1.4; p = 0.27; power = 0.38) and SBP (F = 2.1; p = 0.10; power = 0.57). The ANCOVA for anxiety revealed significantly lower STAI scores in the control group (F = 3.8; p = 0.003) compared with the experimental group. Independent t test analysis for the total doses of fentanyl and midazolam were found to be F = 0.08, p = 0.78 and F = 0.38, p = 0.54, respectively. Conclusion A music intervention on participants with a brain aneurysm or AVM undergoing cerebral angiography did not have a statistically significant impact on reducing the stress response, anxiety or medication requirements. Interestingly, participants in the control group had significantly less anxiety after their angiogram than did participants in the experimental group. This pilot study sets the stage for future research to further examine these findings. C1 [Vanderboom, Teresa L.; Arcari, Patricia M.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Duffy, Mary E.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Vanderboom, TL (reprint author), Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, 55 Fruit St,Gray 241, Boston, MA 02114 USA. EM tvanderboom@partners.org FU Yvonne L Munn Center for Nursing Research at Massachusetts General Hospital; Theta Alpha Chapter of the Sigma Theta Tau International Honor Society of Nursing FX Funding Yvonne L Munn Center for Nursing Research at Massachusetts General Hospital: Nursing Research Award $1500.00. Theta Alpha Chapter of the Sigma Theta Tau International Honor Society of Nursing: Anne K Kibrick Research Award $750.00. NR 25 TC 3 Z9 3 U1 0 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAY PY 2012 VL 4 IS 3 BP 229 EP 233 DI 10.1136/neurintsurg-2011-010052 PG 5 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 925SV UT WOS:000302782600031 PM 21990511 ER PT J AU Nelson, PT Alafuzoff, I Bigio, EH Bouras, C Braak, H Cairns, NJ Castellani, RJ Crain, BJ Davies, P Del Tredici, K Duyckaerts, C Frosch, MP Haroutunian, V Hof, PR Hulette, CM Hyman, BT Iwatsubo, T Jellinger, KA Jicha, GA Kovari, E Kukull, WA Leverenz, JB Love, S Mackenzie, IR Mann, DM Masliah, E McKee, AC Montine, TJ Morris, JC Schneider, JA Sonnen, JA Thal, DR Trojanowski, JQ Troncoso, JC Wisniewski, T Woltjer, RL Beach, TG AF Nelson, Peter T. Alafuzoff, Irina Bigio, Eileen H. Bouras, Constantin Braak, Heiko Cairns, Nigel J. Castellani, Rudolph J. Crain, Barbara J. Davies, Peter Del Tredici, Kelly Duyckaerts, Charles Frosch, Matthew P. Haroutunian, Vahram Hof, Patrick R. Hulette, Christine M. Hyman, Bradley T. Iwatsubo, Takeshi Jellinger, Kurt A. Jicha, Gregory A. Koevari, Enikoe Kukull, Walter A. Leverenz, James B. Love, Seth Mackenzie, Ian R. Mann, David M. Masliah, Eliezer McKee, Ann C. Montine, Thomas J. Morris, John C. Schneider, Julie A. Sonnen, Joshua A. Thal, Dietmar R. Trojanowski, John Q. Troncoso, Juan C. Wisniewski, Thomas Woltjer, Randall L. Beach, Thomas G. TI Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Review DE Aging; Alzheimer disease; Amyloid; Dementia; Epidemiology; Neuropathology; MAPT; Neurofibrillary tangles ID PARKINSONISM-DEMENTIA COMPLEX; FRONTOTEMPORAL LOBAR DEGENERATION; NEUROFIBRILLARY TANGLE FORMATION; AMYOTROPHIC-LATERAL-SCLEROSIS; PAIRED HELICAL FILAMENTS; MINI-MENTAL-STATE; IMPAIR SYNAPTIC PLASTICITY; POSTERIOR CORTICAL ATROPHY; GRADED INTELLECTUAL STATUS; APOLIPOPROTEIN-E GENOTYPE AB Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. beta-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of AA plaques and neurofibrillary tangles. Although AA plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles. C1 [Nelson, Peter T.; Jicha, Gregory A.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Nelson, Peter T.] Univ Kentucky, Dept Pathol, Lexington, KY 40536 USA. [Jicha, Gregory A.] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. [Alafuzoff, Irina] Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, Uppsala, Sweden. [Bigio, Eileen H.] Northwestern Univ, Dept Pathol, NW Alzheimer Dis Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Bouras, Constantin; Koevari, Enikoe] Univ Geneva, Sch Med, Dept Psychiat, CH-1211 Geneva, Switzerland. [Braak, Heiko; Del Tredici, Kelly] Univ Ulm, Dept Neurol, Sect Clin Neuroanat, D-7900 Ulm, Germany. [Thal, Dietmar R.] Univ Ulm, Inst Pathol, Neuropathol Lab, Ulm, Germany. [Cairns, Nigel J.; Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Cairns, Nigel J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Castellani, Rudolph J.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Crain, Barbara J.; Troncoso, Juan C.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. [Crain, Barbara J.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. [Troncoso, Juan C.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Davies, Peter] Albert Einstein Univ, Dept Pathol, Feinstein Inst Med Res, Manhasset, NY USA. [Davies, Peter] Albert Einstein Univ, Dominick P Purpura Dept Neurosciencey, Feinstein Inst Med Res, Manhasset, NY USA. [Duyckaerts, Charles] Hop La Pitie Salpetriere, Serv Neuropathol Raymond Escourolle, Paris, France. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA USA. [Hyman, Bradley T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Haroutunian, Vahram] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Hulette, Christine M.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA. [Hulette, Christine M.] Duke Univ, Sch Med, Dept Neurol, Durham, NC USA. [Iwatsubo, Takeshi] Univ Tokyo, Dept Neuropathol, Grad Sch Med, Tokyo, Japan. [Jellinger, Kurt A.] Inst Clin Neurobiol, Vienna, Austria. [Leverenz, James B.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Kukull, Walter A.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Leverenz, James B.; Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Love, Seth] Univ Bristol, Dept Neuropathol, Inst Clin Neurosci, Frenchay Hosp, Bristol, Avon, England. [Love, Seth] Univ Bristol, Sch Clin Sci, Bristol, Avon, England. [Mackenzie, Ian R.] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada. [Mann, David M.] Univ Manchester, Hope Hosp, Dept Neuropathol, Salford M6 8HD, Lancs, England. [Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. [Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA. [McKee, Ann C.] Boston Univ, Dept Pathol, Bedford, MA USA. [McKee, Ann C.] Boston Univ, Bedford Vet Adm Med Ctr, Bedford, MA USA. Rush Univ, Med Ctr, Dept Pathol Sci, Chicago, IL 60612 USA. Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. Rush Univ, Rush Univ Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res,Inst Aging, Philadelphia, PA 19104 USA. [Wisniewski, Thomas] NYU, Dept Pathol, Langone Med Ctr, New York, NY 10016 USA. [Wisniewski, Thomas] NYU, Dept Neurol, Langone Med Ctr, New York, NY 10016 USA. [Wisniewski, Thomas] NYU, Dept Psychiat, Langone Med Ctr, New York, NY 10016 USA. [Wisniewski, Thomas] NYU, Langone Med Ctr, Alzheimers Dis Ctr, New York, NY USA. [Woltjer, Randall L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Beach, Thomas G.] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Sun City, AZ USA. RP Nelson, PT (reprint author), Univ Kentucky, Sanders Brown Ctr Aging, Room 311,800 S Limestone, Lexington, KY 40536 USA. EM pnels2@email.uky.edu RI Love, Seth/E-6545-2012; Sonnen, 37382016/H-3738-2016; OI Sonnen, 37382016/0000-0001-9267-8705; Kukull, Walter/0000-0001-8761-9014; Wisniewski, Thomas/0000-0002-3379-8966; Mann, Devin/0000-0002-2099-0852 FU National Institutes of Health/National Alzheimer's Coordinating Center [AG05136, AG02219, AG13854, AG05138, AG06647, AG10124, AG016976, AG035071, AG08051, AG008017, AG10161, AG15819, AG028383, AG05681]; Deutsche Forschungsgemeinschaft; Alzheimer Forschung Initiative; Michael J. Fox Foundation for Parkinson's Research; Medical Research Council (UK); Alzheimer's Research UK; Alzheimer's Society; Alzheimer's Association; BRACE FX Supported by Grants AG05136, AG02219, AG13854, AG05138, AG06647, AG10124, AG016976, AG035071, AG08051, AG008017, AG10161, AG15819, AG028383, and AG05681 from the National Institutes of Health/National Alzheimer's Coordinating Center. Additional grants were from the Deutsche Forschungsgemeinschaft, Alzheimer Forschung Initiative, Michael J. Fox Foundation for Parkinson's Research, Medical Research Council (UK), Alzheimer's Research UK, Alzheimer's Society, Alzheimer's Association and BRACE. NR 353 TC 319 Z9 325 U1 13 U2 92 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2012 VL 71 IS 5 BP 362 EP 381 DI 10.1097/NEN.0b013e31825018f7 PG 20 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 929JI UT WOS:000303056900001 PM 22487856 ER PT J AU Wilkinson, HA AF Wilkinson, Harold A. TI Unintended durotomy SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wilkinson, HA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD MAY PY 2012 VL 16 IS 5 BP 520 EP 520 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 929TU UT WOS:000303089400016 PM 22404143 ER PT J AU Katz, ML Laffel, LM Perrin, JM Kuhlthau, K AF Katz, Michelle L. Laffel, Lori M. Perrin, James M. Kuhlthau, Karen TI Impact of Type 1 Diabetes Mellitus on the Family is Reduced with the Medical Home, Care Coordination, and Family-Centered Care SO JOURNAL OF PEDIATRICS LA English DT Article ID CHILDREN; BURDEN; NEEDS AB Objectives To examine whether the medical home, care coordination, or family-centered care was associated with less impact of type 1 diabetes mellitus (T1D) on families' work, finances, time, and school attendance. Study design With the 2005 to 2006 National Survey of Children with Special Health Care Needs, we compared impact in children with T1D (n = 583) with that in children with other special health care needs (n = 39 944) and children without special health care needs (n = 4945). We modeled the associations of the medical home, care coordination, and family-centered care with family impact in T1D. Results Seventy-five percent of families of children with T1D reported a major impact compared with 45% of families of children with special health care needs (P < .0001) and 17% of families of children without special health care needs (P < .0001). In families of children with T1D, 35% reported restricting work, 38% reported financial impact, 41% reported medical expenses >$1000/year, 24% reported spending >= 11 hours/week caring or coordination care, and 20% reported >= 11 school absences/year. The medical home, care coordination, and family-centered care were associated with less work and financial impact. Conclusions In childhood T1D, most families experience major impact. Better systems of health care delivery may help families reduce some of this impact. (J Pediatr 2012; 160: 861-7). C1 [Katz, Michelle L.; Laffel, Lori M.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Katz, Michelle L.; Perrin, James M.; Kuhlthau, Karen] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. RP Katz, ML (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM michelle.katz@joslin.harvard.edu FU Health Resources and Services Administration [T32 HP10018]; NIH [T32 DK007260-35]; Katherine Adler Astrove Youth Education Fund; Joslin Diabetes Center FX M.K. is supported by a Health Resources and Services Administration grant (T32 HP10018) to the Harvard Pediatric Health Services Research Fellowship Program and an NIH grant (T32 DK007260-35). L.L. is supported by the Katherine Adler Astrove Youth Education Fund and Maria Griffin Drury Fund at Joslin Diabetes Center. Any analyses, interpretations, or conclusions are reached by the authors and not the National Center for Health Statistics, which is responsible only for the initial data. The authors declare no conflicts of interest. NR 24 TC 22 Z9 23 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2012 VL 160 IS 5 BP 861 EP 867 DI 10.1016/j.jpeds.2011.10.010 PG 7 WC Pediatrics SC Pediatrics GA 928OQ UT WOS:000302992800034 PM 22133424 ER PT J AU Furmaga, H Sadhu, M Frazer, A AF Furmaga, Havan Sadhu, Mohona Frazer, Alan TI Comparison of Delta FosB Immunoreactivity Induced by Vagal Nerve Stimulation with That Caused by Pharmacologically Diverse Antidepressants SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TREATMENT-RESISTANT DEPRESSION; CEREBRAL-BLOOD-FLOW; VAGUS NERVE; C-FOS; RAT-BRAIN; MESSENGER-RNA; LONG-TERM; PERIAQUEDUCTAL GRAY; MEDULLA-OBLONGATA; LOCUS COERULEUS AB Vagal nerve stimulation (VNS) has been approved for treatment of refractory depression. However, there have been few, if any, studies directly comparing the effects produced by VNS in animals with those caused by antidepressants, particularly using clinically relevant stimulation parameters in nonanesthetized animals. In this study, Delta FosB immunohistochemistry was used to evaluate different brain regions activated by long-term administration of VNS. Effects of VNS were compared with those caused by sertraline or desipramine (DMI). Double-labeling of Delta FosB and serotonin was used to determine whether serotonergic neurons in the dorsal raphe nucleus (DRN) were activated by long-term VNS. VNS significantly increased Delta FosB staining in the nucleus tractus solitarius (NTS), parabrachial nucleus (PBN), locus ceruleus (LC), and DRN, as well as in many cortical and limbic areas of brain including those involved in mood and cognition. Most, but not all, of these effects were seen also upon long-term treatments of rats with sertraline or DMI. Some areas where VNS increased Delta FosB (e. g., the NTS, PBN, LC, and peripeduncular nucleus) were not affected significantly by either drug. Sertraline was similar to VNS in causing an increase in the DRN whereas DMI did not. Double-labeling of the DRN with Delta FosB and an antibody for serotonin revealed that only a small percentage of Delta FosB staining in the DRN colocalized with serotonergic neurons. The effects of VNS were somewhat more widespread than those caused by the antidepressants. The increases in Delta FosB produced by VNS were either equivalent to and/or more robust than those seen with antidepressants. C1 [Furmaga, Havan; Frazer, Alan] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Sadhu, Mohona] Univ Texas Austin, Austin, TX 78712 USA. [Frazer, Alan] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Frazer, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr,Mail Code 7764, San Antonio, TX 78229 USA. EM frazer@uthscsa.edu FU National Institutes of Health National Institute of Mental Health [MH082933]; Cyberonics Inc. FX This work was supported by the National Institutes of Health National Institute of Mental Health [Grant MH082933]. The electrodes, VNS stimulators, and dummy stimulators were gifts from Cyberonics, Inc. (Houston, TX).; Dr. Frazer has served on advisory boards for Lundbeck and for Takeda in the last 3 years. Previously, Dr. Frazer had received financial compensation as a consultant for Cyberonics Inc. and had also obtained grant support from them for a preclinical study. NR 45 TC 9 Z9 9 U1 0 U2 1 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 MAY PY 2012 VL 341 IS 2 BP 317 EP 325 DI 10.1124/jpet.111.188953 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 927JM UT WOS:000302903500002 PM 22286499 ER PT J AU Pastor, R Reed, C Meyer, PJ McKinnon, C Ryabinin, AE Phillips, TJ AF Pastor, Raul Reed, Cheryl Meyer, Paul J. McKinnon, Carrie Ryabinin, Andrey E. Phillips, Tamara J. TI Role of Corticotropin-Releasing Factor and Corticosterone in Behavioral Sensitization to Ethanol SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DBA/2J MICE; FACTOR CRF; RECEPTOR ANTAGONISTS; CROSS-SENSITIZATION; ADDICTION; ALCOHOL; EXPRESSION; STRESS; RATS; MECHANISMS AB Neuroadaptations underlying sensitization to drugs of abuse seem to influence compulsive drug pursuit and relapse associated with addiction. Our previous data support a role for the corticotropin-releasing factor (CRF) type-1 receptor (CRF 1) in ethanol (EtOH)-induced psychomotor sensitization. CRF 1 is endogenously activated by CRF and urocortin-1. Because genetic deletion of urocortin-1 did not affect EtOH sensitization, we hypothesized that CRF is the important ligand underlying EtOH sensitization. To test this hypothesis, we used heterozygous and homozygous knockout (KO) mice, which lack one or both copies of the gene coding for CRF, and their respective wildtype controls. EtOH sensitization was normal in heterozygous, but absent in homozygous, CRF KO mice. Corticosterone (CORT) levels were drastically reduced only in CRF KO mice. Because CRF/CRF1 initiate EtOH-induced activation of the hypothalamic-pituitary-adrenal axis, we investigated CORT effects on EtOH sensitization. The CORT synthesis inhibitor metyrapone prevented the acquisition, but not the expression, of EtOH sensitization. Exogenous CORT administration sensitized the locomotor response to a subsequent EtOH challenge; we observed, however, that the exogenous CORT levels necessary to induce sensitization to EtOH were significantly higher than those produced by EtOH treatment. Therefore, participation of CORT seems to be necessary, but not sufficient, to explain the role of CRF/CRF1 in the acquisition of sensitization to EtOH. Extra-hypothalamic CRF/CRF1 mechanisms are suggested to be involved in the expression of EtOH sensitization. The present results are consistent with current theories proposing a key role for CRF and CRF1 in drug-induced neuroplasticity, dependence, and addictive behavior. C1 [Pastor, Raul; Reed, Cheryl; Meyer, Paul J.; McKinnon, Carrie; Ryabinin, Andrey E.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Pastor, Raul; Reed, Cheryl; Meyer, Paul J.; McKinnon, Carrie; Ryabinin, Andrey E.; Phillips, Tamara J.] Portland Alcohol Res Ctr, Portland, OR USA. [Phillips, Tamara J.] Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA. [Pastor, Raul] Univ Jaume 1, Area Psicobiol, Castellon de La Plana, Spain. RP Phillips, TJ (reprint author), Portland VA Med Ctr, Res Serv, R&D32,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM phillipt@ohsu.edu FU Department of Veterans Affairs; National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [R01-AA13331, P60-AA010760, R01-AA013738, R24-AA020245, U01016647] FX This work was supported by the Department of Veterans Affairs and the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grants R01-AA13331, P60-AA010760, R01-AA013738, R24-AA020245, U01016647]. NR 44 TC 10 Z9 10 U1 0 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 MAY PY 2012 VL 341 IS 2 BP 455 EP 463 DI 10.1124/jpet.111.190595 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 927JM UT WOS:000302903500015 PM 22333290 ER PT J AU Linskey, KR Kroshinsky, D Mihm, MC Hoang, MP AF Linskey, Katy R. Kroshinsky, Daniela Mihm, Martin C., Jr. Hoang, Mai P. TI Immunoglobulin-A-associated small-vessel vasculitis: A 10-year experience at the Massachusetts General Hospital SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE direct immunofluorescence; Henoch-Schonlein purpura; IgA; IgA-vasculitis; leukocytoclastic vasculitis ID HENOCH-SCHONLEIN PURPURA; RHEUMATOLOGY 1990 CRITERIA; CLINICALLY NORMAL SKIN; IGA-IMMUNE-COMPLEXES; TERM FOLLOW-UP; LEUKOCYTOCLASTIC VASCULITIS; CUTANEOUS VASCULITIS; HYPERSENSITIVITY VASCULITIS; DIRECT IMMUNOFLUORESCENCE; CLASSIFICATION CRITERIA AB Background: The main morbidity associated with Henoch-Schonlein purpura (HSP) results from glomerulonephritis and associated renal symptoms; thus early and accurate diagnosis would have follow-up implications. Objective: To determine the strength of association of IgA vascular deposition with HSP in a mostly adult and hospital-based population. Methods: We retrospectively analyzed patients with a histologic diagnosis of cutaneous leukocytoclastic vasculitis (LCV) and corresponding direct immunofluorescence (DIF) studies between 2000 and 2010. European League Against Rheumatism criteria were used to diagnose HSP cases clinically. They are purpura or petechiae with lower limb predominance plus at least one of the following: abdominal pain, LCV or proliferative glomerulonephritis with predominant IgA deposit, arthritis/arthralgia, or proteinuria or hematuria. Results: IgA positivity was significantly associated with HSP (P = .0001), and yielded sensitivity of 81% and specificity of 83%. Positive predictive value of IgA staining for HSP was 84%, and negative predictive value was 81%. No other histologic features were significantly associated with HSP. Limitations: Our sample size was relatively small and mostly an inpatient population (79%). We may have missed cases of HSP and a subset of IgA + LCV patients who did not have clinical findings of HSP by limiting our series to only cases with DIF studies done. Certain clinical data may be incomplete since they were collected retrospectively. Conclusions: Our study confirms a strong association between IgA deposits on DIF and HSP, but also highlights a subset of HSP cases in which vascular IgA deposition in the skin appears to be negative. (J Am Acad Dermatol 2012;66:813-22.) C1 [Hoang, Mai P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. [Mihm, Martin C., Jr.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. [Linskey, Katy R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hoang, MP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatopathol Unit, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org NR 48 TC 16 Z9 17 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2012 VL 66 IS 5 BP 813 EP 822 DI 10.1016/j.jaad.2011.06.012 PG 10 WC Dermatology SC Dermatology GA 926UZ UT WOS:000302858700023 PM 21798626 ER PT J AU Iwasaki, JK Srivastava, D Moy, RL Lin, HJ Kouba, DJ AF Iwasaki, Julie K. Srivastava, Divya Moy, Ronald L. Lin, Henry J. Kouba, David J. TI The molecular genetics underlying basal cell carcinoma pathogenesis and links to targeted therapeutics SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE carcinoma; basal cell; sonic hedgehog ID NONMELANOMA SKIN-CANCER; HEDGEHOG SIGNALING PATHWAY; CENTRAL-NERVOUS-SYSTEM; SONIC HEDGEHOG; HUMAN HOMOLOG; N-MYC; EXPRESSION; MUTATIONS; PROLIFERATION; INHIBITION AB Mutations in the sonic hedgehog signaling pathway play a key role in the development of basal cell carcinomas. Specifically, mutations in the PTCH1 (also known as PTCH or PTC1) and SMO genes cause tumor formation through constitutive activation of the pathway. Misregulation of the pathway has also been implicated in the nevoid basal cell carcinoma syndrome and other tumors. Understanding the function of the sonic hedgehog pathway has led to novel strategies for treatment. In this review we highlight the role of the pathway in the pathogenesis of basal cell carcinoma and review potential targeted therapies. (J Am Acad Dermatol 2012;66:e167-78.) C1 [Kouba, David J.] Henry Ford Hlth Syst, Dept Dermatol, Div Mohs Microg Surg, Detroit, MI 48202 USA. [Srivastava, Divya] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Moy, Ronald L.; Lin, Henry J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Moy, Ronald L.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. [Lin, Henry J.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA. [Lin, Henry J.] Harbor UCLA Med Ctr, Div Med Genet, Torrance, CA 90509 USA. [Kouba, David J.] Toledo Clin Dermasurg & Laser Ctr, Toledo, OH USA. RP Kouba, DJ (reprint author), Henry Ford Hlth Syst, Dept Dermatol, Div Mohs Microg Surg, 3031 W Grand Blvd,Suite 800, Detroit, MI 48202 USA. EM dkouba1@hfhs.org NR 49 TC 22 Z9 22 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2012 VL 66 IS 5 BP E167 EP E178 DI 10.1016/j.jaad.2010.06.054 PG 12 WC Dermatology SC Dermatology GA 926UZ UT WOS:000302858700005 PM 20800318 ER PT J AU Lanham, HJ Leykum, LK McDaniel, RR AF Lanham, Holly Jordan Leykum, Luci K. McDaniel, Reuben R., Jr. TI Same organization, same electronic health records (EHRs) system, different use: exploring the linkage between practice member communication patterns and EHR use patterns in an ambulatory care setting SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID COMPLEX ADAPTIVE SYSTEMS; INFORMATION-SYSTEMS; QUALITY; TECHNOLOGY; IMPACT; STATES; COSTS; TEAMS AB Objective Despite efforts made by ambulatory care organizations to standardize the use of electronic health records (EHRs), practices often incorporate these systems into their work differently from each other. One potential factor contributing to these differences is within-practice communication patterns. The authors explore the linkage between within-practice communication patterns and practice-level EHR use patterns. Design Qualitative study of six practices operating within the same multi-specialty ambulatory care organization using the same EHR system. Semistructured interviews and direct observation were conducted with all physicians, nurses, medical assistants, practice managers, and non-clinical staff from each practice. Measurements An existing model of practice relationships was used to analyze communication patterns within the practices. Practice-level EHR use was defined and analyzed as the ways in which a practice uses an EHR as a collective or a group-including the degree of feature use, level of EHR-enabled communication, and frequency that EHR use changes in a practice. Interview and observation data were analyzed for themes. Based on these themes, within-practice communication patterns were categorized as fragmented or cohesive, and practice-level EHR use patterns were categorized as heterogeneous or homogeneous. Practices where EHR use was uniformly high across all users were further categorized as having standardized EHR use. Communication patterns and EHR use patterns were compared across the six practices. Results Within-practice communication patterns were associated with practice-level EHR use patterns. In practices where communication patterns were fragmented, EHR use was heterogeneous. In practices where communication patterns were cohesive, EHR use was homogeneous. Additional analysis revealed that practices that had achieved standardized EHR use (uniformly high EHR use across all users) exhibited high levels of mindfulness and respectful interaction, whereas practices that were furthest from achieving standardized EHR use exhibited low levels of mindfulness and respectful interaction. Conclusion Within-practice communication patterns provide a unique perspective for exploring the issue of standardization in EHR use. A major fallacy of setting homogeneous EHR use as the goal for practice-level EHR use is that practices with uniformly low EHR use could be considered successful. Achieving uniformly high EHR use across all users in a practice is more consistent with the goals of current EHR adoption and use efforts. It was found that some communication patterns among practice members may enable more standardized EHR use than others. Understanding the linkage between communication patterns and EHR use can inform understanding of the human element in EHR use and may provide key lessons for the implementation of EHRs and other health information technologies. C1 [Lanham, Holly Jordan; Leykum, Luci K.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Lanham, Holly Jordan; Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Lanham, Holly Jordan] Univ Texas Austin, McCombs Sch Business, Austin, TX 78712 USA. [McDaniel, Reuben R., Jr.] McCombs Sch Business, Dept Informat Risk & Operat, Austin, TX USA. RP Lanham, HJ (reprint author), 1 Univ Stn,B6000, Austin, TX 78712 USA. EM lanham@uthscsa.edu FU South Texas Veterans Health Care System, Veterans Evidence Based Research Dissemination and Implementation Center (VERDICT), San Antonio, Texas, United States; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [REA 05-129, CDA 07-022]; LKL; South Texas Veterans Health Care System; IC2 Institute of The University of Texas at Austin FX This material is the result of work supported with resources and the use of facilities at the South Texas Veterans Health Care System, Veterans Evidence Based Research Dissemination and Implementation Center (VERDICT), San Antonio, Texas, United States. The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (REA 05-129, CDA 07-022). Investigator salary support for LKL is provided through this funding, and through the South Texas Veterans Health Care System. RRM receives support from the IC2 Institute of The University of Texas at Austin. We would like to express our gratitude to the Chief Information Officer, physician leadership, EHR staff, and the physicians, nurses and other healthcare professionals that participated in this study. We would also like to acknowledge Madhu C Reddy and two anonymous reviewers for their helpful comments on previous versions of this manuscript. NR 57 TC 16 Z9 16 U1 0 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY PY 2012 VL 19 IS 3 BP 382 EP 391 DI 10.1136/amiajnl-2011-000263 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 925TE UT WOS:000302783600010 PM 21846780 ER PT J AU Li, M Tilles, AW Milwid, JM Hammad, M Lee, J Yarmush, ML Parekkadan, B AF Li, Matthew Tilles, Arno W. Milwid, Jack M. Hammad, Mohamed Lee, Jungwoo Yarmush, Martin L. Parekkadan, Biju TI Phenotypic and functional characterization of human bone marrow stromal cells in hollow-fibre bioreactors SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE LA English DT Article DE mesenchymal stem cell; dialysis; acute kidney failure ID MESENCHYMAL STEM-CELLS; VERSUS-HOST-DISEASE; MYOCARDIAL-INFARCTION; RENAL-FAILURE; IN-VITRO; ACTIVATION; MICE; LUNG; VIVO; INTERLEUKIN-6-DEFICIENT AB The transplantation of human bone marrow stromal cells (BMSCs) is a novel immunotherapeutic approach that is currently being explored in many clinical settings. Evidence suggests that the efficacy of cell transplantation is directly associated with soluble factors released by human BMSCs. In order to harness these secreted factors, we integrated BMSCs into large-scale hollow-fibre bioreactor devices in which the cells, separated by a semipermeable polyethersulphone (PES) membrane, can directly and continuously release therapeutic factors into the blood stream. BMSCs were found to be rapidly adherent and exhibited long-term viability on PES fibres. The cells also preserved their immunophenotype under physiological fluid flow rates in the bioreactor, and exhibited no signs of differentiation during device operation, but still retained the capacity to differentiate into osteoblastic lineages. BMSC devices released growth factors and cytokines at comparable levels on a per-cell basis to conventional cell culture platforms. Finally, we utilized a potency assay to demonstrate the therapeutic potential of the collected secreted factors from the BMSC devices. In summary, we have shown that culturing BMSCs in a large-scale hollow-fibre bioreactor is feasible without deleterious effects on phenotype, thus providing a platform for collecting and delivering the paracrine secretions of these cells. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Li, Matthew; Milwid, Jack M.; Hammad, Mohamed; Lee, Jungwoo; Yarmush, Martin L.; Parekkadan, Biju] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv,Shriners Hosp Children, Boston, MA USA. [Milwid, Jack M.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tilles, Arno W.] Sentien Biotechnol Inc, Medford, MA USA. RP Parekkadan, B (reprint author), 51 Blossom St, Boston, MA 02115 USA. EM biju_parekkadan@hms.harvard.edu RI Lee, Jungwoo/I-4219-2013 FU National Institutes of Health [K01DK087770, R21DK085267, R01DK43371]; Shriners Hospitals for Children FX The authors would like to thank Jane Braunsky, Goetze Friederichs and Denny Treu for the donation of NxStage dialysers and technical guidance on use of their cartridges. This work was partially supported by the National Institutes of Health, Grant Nos K01DK087770 (to BP), R21DK085267 (to MLY) and R01DK43371 (to MLY), and the Shriners Hospitals for Children (MLY, BP). NR 44 TC 3 Z9 4 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-6254 J9 J TISSUE ENG REGEN M JI J. Tissue Eng. Regen. Med. PD MAY PY 2012 VL 6 IS 5 BP 369 EP 377 DI 10.1002/term.439 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical SC Cell Biology; Biotechnology & Applied Microbiology; Engineering GA 928RO UT WOS:000303001200004 PM 21710576 ER PT J AU Carlson, JM Listgarten, J Pfeifer, N Tan, V Kadie, C Walker, BD Ndung'u, T Shapiro, R Frater, J Brumme, ZL Goulder, PJR Heckerman, D AF Carlson, Jonathan M. Listgarten, Jennifer Pfeifer, Nico Tan, Vincent Kadie, Carl Walker, Bruce D. Ndung'u, Thumbi Shapiro, Roger Frater, John Brumme, Zabrina L. Goulder, Philip J. R. Heckerman, David TI Widespread Impact of HLA Restriction on Immune Control and Escape Pathways of HIV-1 SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MHC-CLASS-I; T-LYMPHOCYTE RESPONSE; VIRAL LOAD; SELECTION PRESSURE; CELL RESPONSES; CTL EPITOPES; CONSERVED REGIONS; ELITE CONTROLLERS; GAG AB The promiscuous presentation of epitopes by similar HLA class I alleles holds promise for a universal T-cell-based HIV-1 vaccine. However, in some instances, cytotoxic T lymphocytes (CTL) restricted by HLA alleles with similar or identical binding motifs are known to target epitopes at different frequencies, with different functional avidities and with different apparent clinical outcomes. Such differences may be illuminated by the association of similar HLA alleles with distinctive escape pathways. Using a novel computational method featuring phylogenetically corrected odds ratios, we systematically analyzed differential patterns of immune escape across all optimally defined epitopes in Gag, Pol, and Nef in 2,126 HIV-1 clade C-infected adults. Overall, we identified 301 polymorphisms in 90 epitopes associated with HLA alleles belonging to shared supertypes. We detected differential escape in 37 of 38 epitopes restricted by more than one allele, which included 278 instances of differential escape at the polymorphism level. The majority (66 to 97%) of these resulted from the selection of unique HLA-specific polymorphisms rather than differential epitope targeting rates, as confirmed by gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot assay (ELISPOT) data. Discordant associations between HLA alleles and viral load were frequently observed between allele pairs that selected for differential escape. Furthermore, the total number of associated polymorphisms strongly correlated with average viral load. These studies confirm that differential escape is a widespread phenomenon and may be the norm when two alleles present the same epitope. Given the clinical correlates of immune escape, such heterogeneity suggests that certain epitopes will lead to discordant outcomes if applied universally in a vaccine. C1 [Carlson, Jonathan M.; Listgarten, Jennifer; Pfeifer, Nico; Tan, Vincent; Heckerman, David] Microsoft Res, ESci Grp, Los Angeles, CA USA. [Kadie, Carl] Microsoft Res, ESci Grp, Redmond, WA USA. [Walker, Bruce D.; Ndung'u, Thumbi] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Walker, Bruce D.; Ndung'u, Thumbi; Goulder, Philip J. R.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Shapiro, Roger] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Frater, John] Univ Oxford, Nuffield Dept Clin Med, Oxford, England. [Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Brumme, Zabrina L.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Oxford, England. RP Carlson, JM (reprint author), Microsoft Res, ESci Grp, Los Angeles, CA USA. EM carlson@microsoft.com RI Pfeifer, Nico/G-1559-2016; OI Pfeifer, Nico/0000-0002-4647-8566; Ndung'u, Thumbi/0000-0003-2962-3992 FU Canadian Institutes of Health Research (CIHR); NIH [NO1-A1-15422, 2RO1AI46995-06, R01AI067073]; South African AIDS Vaccine Initiative; Mark and Lisa Schwartz Foundation FX J.M.C., J.L., N.P., V.T., C.K., and D.H. are employed by Microsoft Corp. Z.L.B. is supported by a New Investigator Award from the Canadian Institutes of Health Research (CIHR). The Durban cohort was supported by the NIH (contract NO1-A1-15422, 2RO1AI46995-06, R01AI067073), the South African AIDS Vaccine Initiative, and the Mark and Lisa Schwartz Foundation. T.N. holds the South African DST/NRF Chair in Systems Biology of HIV/AIDS. NR 81 TC 56 Z9 56 U1 1 U2 3 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 MAY PY 2012 VL 86 IS 9 BP 5230 EP 5243 DI 10.1128/JVI.06728-11 PG 14 WC Virology SC Virology GA 925RD UT WOS:000302777800043 PM 22379086 ER PT J AU Cureton, DK Harbison, CE Cocucci, E Parrish, CR Kirchhausen, T AF Cureton, David K. Harbison, Carole E. Cocucci, Emanuele Parrish, Colin R. Kirchhausen, Tom TI Limited Transferrin Receptor Clustering Allows Rapid Diffusion of Canine Parvovirus into Clathrin Endocytic Structures SO JOURNAL OF VIROLOGY LA English DT Article ID FELINE PARVOVIRUSES; MEDIATED ENDOCYTOSIS; CAPSID STRUCTURE; PLASMA-MEMBRANE; HOST RANGES; VIRUS; CELL; BINDING; ENTRY; INFECTION AB Viral pathogens usurp cell surface receptors to access clathrin endocytic structures, yet the mechanisms of virus incorporation into these structures remain incompletely understood. Here we used fluorescence microscopy to directly visualize the association of single canine parvovirus (CPV) capsids with cellular transferrin receptors (TfR) on the surfaces of live feline cells and to monitor how these CPV-TfR complexes access endocytic structures. We found that most capsids associated with fewer than five TfRs and that similar to 25% of TfR-bound capsids laterally diffused into assembling clathrin-coated pits less than 30 s after attachment. Capsids that did not encounter a coated pit dissociated from the cell surface with a half-life of similar to 30 s. Together, our results show how CPV exploits the natural mechanism of TfR endocytosis to engage the clathrin endocytic pathway and reveal that the low affinity of capsids for feline TfRs limits the residence time of capsids on the cell surface and thus the efficiency of virus internalization. C1 [Cureton, David K.; Cocucci, Emanuele; Kirchhausen, Tom] Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. [Cureton, David K.; Cocucci, Emanuele; Kirchhausen, Tom] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. [Harbison, Carole E.; Parrish, Colin R.] Cornell Univ, Coll Vet Med, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA. RP Kirchhausen, T (reprint author), Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. EM crp3@cornell.edu; kirchhausen@crystal.harvard.edu FU NIH [AI092571, AI028385, U54 AI057159] FX This work was funded by NIH grants AI092571 and AI028385 to C.R.P. and U54 AI057159 (New England Regional Center of Excellence in Biodefence and Emerging Infectious Diseases [NERCE BEID]) to T.K. NR 51 TC 16 Z9 16 U1 0 U2 11 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 MAY PY 2012 VL 86 IS 9 BP 5330 EP 5340 DI 10.1128/JVI.07194-11 PG 11 WC Virology SC Virology GA 925RD UT WOS:000302777800052 PM 22357278 ER PT J AU Zhong, YF Wu, YW Liu, RJ Deng, YY Mallipattu, SK Klotman, PE Chuang, PY He, JC AF Zhong, Yifei Wu, Yingwei Liu, Ruijie Deng, Yueyi Mallipattu, Sandeep K. Klotman, Paul E. Chuang, Peter Y. He, John C. TI Roflumilast enhances the renal protective effects of retinoids in an HIV-1 transgenic mouse model of rapidly progressive renal failure SO KIDNEY INTERNATIONAL LA English DT Article DE collapsing glomerulopathy; glomerular disease; HIV nephropathy; podocyte; signaling ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; HIV-1-ASSOCIATED NEPHROPATHY; ANTIRETROVIRAL THERAPY; CAMP PATHWAY; ACID; PODOCYTE; EXPRESSION; CREB; DEDIFFERENTIATION; PHOSPHORYLATION AB Retinoic acid decreases proteinuria and glomerulosclerosis in several animal models of kidney disease by protecting podocytes from injury. Our recent in vitro studies suggest that all-trans retinoic acid induces podocyte differentiation by activating the retinoic acid receptor-alpha (RAR alpha)/cAMP/PKA/CREB pathway. When used in combination with all-trans retinoic acid, an inhibitor of phosphodiesterase 4 further enhanced podocyte differentiation by increasing intracellular cAMP. Additionally, we found that Am580, a specific RAR alpha agonist, has similar renal protective effects as all-trans retinoic acid in a rederived colony of HIV-1 transgenic mice with rapidly progressive renal failure (HIV-Tg) that mimics human HIV-associated nephropathy. Treatment with either the inhibitor of phosphodiesterase 4, roflumilast, or Am580 significantly reduced proteinuria, attenuated kidney injury, and improved podocyte differentiation in these HIV-Tg mice. Additional renal protective effects were found when roflumilast was combined with Am580. Consistent with the in vitro data, glomeruli from HIV-Tg mice treated with both Am580 and roflumilast had more active phosphorylated CREB than with either agent alone. Thus, phosphodiesterase 4 inhibitors could be used in combination with RAR alpha agonists to provide additional renal protection. Kidney International (2012) 81, 856-864; doi:10.1038/ki.2011.467; published online 18 January 2012 C1 [Zhong, Yifei; Liu, Ruijie; Mallipattu, Sandeep K.; Chuang, Peter Y.; He, John C.] Mt Sinai Sch Med, Div Nephrol, Dept Med, New York, NY 10029 USA. [Zhong, Yifei; Deng, Yueyi] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Nephrol, Shanghai, Peoples R China. [Wu, Yingwei] Tongji Univ, Shanghai E Hosp, Shanghai 200092, Peoples R China. [Klotman, Paul E.] Baylor Coll Med, Houston, TX 77030 USA. [He, John C.] James J Peters VA Med Ctr, Bronx, NY USA. RP He, JC (reprint author), Mt Sinai Sch Med, Div Nephrol, Dept Med, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM cijiang.he@mssm.edu RI Mallipattu , Sandeep/M-7009-2014 FU NIH [1R01DK078897, 1R01DK088541, P01-DK-56492, 5K08DK082760]; VA Merit Award FX JCH is supported by NIH 1R01DK078897, 1R01DK088541, P01-DK-56492, and VA Merit Award; PYC is supported by NIH 5K08DK082760. NR 34 TC 10 Z9 11 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2012 VL 81 IS 9 BP 856 EP 864 DI 10.1038/ki.2011.467 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 926XF UT WOS:000302864500009 PM 22258322 ER PT J AU Shargorodsky, J Hartnick, CJ Lee, GS AF Shargorodsky, Josef Hartnick, Christopher J. Lee, Gi Soo TI Dexamethasone and postoperative bleeding after tonsillectomy and adenotonsillectomy in children: A meta-analysis of prospective studies SO LARYNGOSCOPE LA English DT Article DE Tonsils; bleeding; steroids; dexamethasone; Level of Evidence: 1a ID PEDIATRIC TONSILLECTOMY; PREOPERATIVE DEXAMETHASONE; INTRAVENOUS DEXAMETHASONE; FIBRINOLYTIC-ACTIVITY; PLATELET-AGGREGATION; CLINICAL-TRIALS; ORAL INTAKE; PAIN; STEROIDS; MORBIDITY AB Objectives/Hypothesis: Tonsillectomy and adenotonsillectomy are common pediatric surgical procedures. Although perioperative administration of dexamethasone is common, recent data indicate a possible association between dexamethasone and increased risk of postoperative hemorrhage. Study Design: Meta-analysis of prospective studies. Methods: Meta-analysis using MEDLINE and EMBASE, including all placebo-controlled prospective studies with perioperative dexamethasone as the intervention and postoperative bleeding as the outcome, in children age < 18 years undergoing tonsillectomy or adenotonsillectomy. The association between any dexamethasone dose and bleeding outcomes was quantified. Dexamethasone dose analyses were performed using meta-regression and stratified dose analysis models. Individuals were pooled using the random effects model, and Mantel Haenszel odds ratios (OR) were used to assess the associations. All P values were two-sided. Results: Twelve studies with 1,180 total participants were included in the meta-analysis. There was no significant association between dexamethasone at any dose and odds of bleeding compared to placebo (OR 1.07; 95% confidence interval [CI], 0.58-1.98; P = .82). There was no significant association between increasing dexamethasone dose and bleeding (regression slope = -1.47, P.10). Stratifying by dose ranges, studies comparing dexamethasone doses in 0.4 to 0.6 mg/kg range to placebo showed significantly increased odds of bleeding (OR 3.14; 95% CI, 1.14-8.65; P=.03). Higher or lower doses were not associated with a difference in bleeding. Conclusions: There was no overall association between dexamethasone administration and postoperative bleeding in children undergoing tonsillectomy or adenotonsillectomy. However, this study cannot exclude the possibility of an association between specific dexamethasone doses and increased odds of bleeding. The results underscore the need for more dedicated prospective studies of this very common intervention. C1 [Shargorodsky, Josef; Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Shargorodsky, Josef; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Lee, Gi Soo] Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, Boston, MA USA. RP Shargorodsky, J (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM josef_shargorodsky@meei.harvard.edu NR 50 TC 15 Z9 15 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2012 VL 122 IS 5 BP 1158 EP 1164 DI 10.1002/lary.21881 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 927XY UT WOS:000302945100040 PM 22447657 ER PT J AU Gallagher, TQ Setlur, J Maturo, S Hartnick, CJ AF Gallagher, Thomas Q. Setlur, Jennifer Maturo, Stephen Hartnick, Christopher J. TI Percutaneous transtracheal needle insufflation: A useful emergency airway adjunct simply constructed from common items found on your anesthesia cart SO LARYNGOSCOPE LA English DT Article DE Transtracheal; needle insufflation; pediatric airway; emergency airway AB Using material already available in the operating room, we describe the construction and application of a percutaneous transtracheal needle insufflation device to be used in pediatric airway emergencies. Our technique of percutaneous needle insufflation using common materials found in the operating room can be a helpful adjunct in a time of need. Quickly constructed and at a minimal cost, the device can be just one of the many useful tools found in the otolaryngologist's airway armamentarium. C1 [Gallagher, Thomas Q.] USN, Med Ctr, Dept Otolaryngol, Portsmouth, VA 23708 USA. [Maturo, Stephen] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Maturo, Stephen] Brooke Army Med Ctr, Dept Otolaryngol, San Antonio, TX USA. RP Gallagher, TQ (reprint author), USN, Med Ctr, Dept Otolaryngol, 620 John Paul Jones Circle, Portsmouth, VA 23708 USA. EM thomas.q.gallagher@med.navy.mil NR 4 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2012 VL 122 IS 5 BP 1178 EP 1180 DI 10.1002/lary.23236 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 927XY UT WOS:000302945100043 PM 22447414 ER PT J AU Ono, S Obara, H Takayanagi, A Tanabe, M Kawachi, S Itano, O Shinoda, M Kitago, M Yagi, H Matsubara, K Tilles, AW Yarmush, ML Chiba, T Du, WL Aiso, S Sakamoto, M Shimizu, N Kitagawa, Y AF Ono, Shigeshi Obara, Hideaki Takayanagi, Atsushi Tanabe, Minoru Kawachi, Shigeyuki Itano, Osamu Shinoda, Masahiro Kitago, Minoru Yagi, Hiroshi Matsubara, Kentaro Tilles, Arno W. Yarmush, Martin L. Chiba, Tomohiro Du, Wenlin Aiso, Sadakazu Sakamoto, Michiie Shimizu, Nobuyoshi Kitagawa, Yuko TI Specific Inhibition of Interleukin-18 Improves Liver Function in Rat Liver Transplantation. SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT 18th Annual International Congress on ILTS CY MAY 16-19, 2012 CL San Francisco, CA SP ILTS C1 [Ono, Shigeshi; Obara, Hideaki; Takayanagi, Atsushi; Tanabe, Minoru; Kawachi, Shigeyuki; Itano, Osamu; Shinoda, Masahiro; Kitago, Minoru; Yagi, Hiroshi; Matsubara, Kentaro; Chiba, Tomohiro; Du, Wenlin; Aiso, Sadakazu; Sakamoto, Michiie; Shimizu, Nobuyoshi; Kitagawa, Yuko] Keio Univ, Sch Med, Tokyo, Japan. [Tilles, Arno W.; Yarmush, Martin L.] Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA USA. [Tilles, Arno W.; Yarmush, Martin L.] Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Surg Survices, Boston, MA USA. [Tilles, Arno W.; Yarmush, Martin L.] Harvard Univ, Sch Med, Boston, MA USA. RI Obara, Hideaki/B-3174-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD MAY PY 2012 VL 18 SU 1 BP S144 EP S144 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 929EE UT WOS:000303043200203 ER PT J AU Henstrom, D Hadlock, T Lindsay, R Knox, CJ Malo, J Vakharia, KT Heaton, JT AF Henstrom, Doug Hadlock, Tessa Lindsay, Robin Knox, Christopher J. Malo, Juan Vakharia, Kalpesh T. Heaton, James T. TI The convergence of facial nerve branches providing whisker pad motor supply in rats: Implications for facial reanimation study SO MUSCLE & NERVE LA English DT Article DE anatomy; facial nerve; movement; rats; vibrissae ID MOVEMENTS; RECOVERY; INJURY; REPAIR AB Introduction: Rodent whisking behavior is supported by the buccal and mandibular branches of the facial nerve, but a description of how these branches converge and contribute to whisker movement is lacking. Methods: Eight rats underwent isolated transection of either the buccal or mandibular branch and subsequent opposite branch transection. Whisking function was analyzed after both transections. Anatomical measurements, and video recording of stimulation to individual branches, were taken from both facial nerves in 10 rats. Results: Normal to near-normal whisking was demonstrated after isolated branch transection. Whisking was eliminated after transection of both branches. The buccal and mandibular branches form a convergence just proximal to the whisker pad, herein called 'distal pes.' Distal to this convergence, we identified consistent anatomy that demonstrated cross-innervation. Conclusion: The overlap of efferent supply to the whisker pad must be considered when studying facial nerve regeneration in the rat facial nerve model. Muscle Nerve 45: 692-697, 2012 C1 [Hadlock, Tessa; Knox, Christopher J.; Malo, Juan; Vakharia, Kalpesh T.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Henstrom, Doug] Univ Iowa, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. [Lindsay, Robin] Bethesda Naval Med Ctr, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA. [Heaton, James T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Hadlock, T (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu FU NINDS NIH HHS [R01 NS071067] NR 17 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD MAY PY 2012 VL 45 IS 5 BP 692 EP 697 DI 10.1002/mus.23232 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 924WV UT WOS:000302722900011 PM 22499096 ER PT J AU Kaye, J Curren, L Anderson, N Edwards, K Fullerton, SM Kanellopoulou, N Lund, D MacArthur, DG Mascalzoni, D Shepherd, J Taylor, PL Terry, SF Winter, SF AF Kaye, Jane Curren, Liam Anderson, Nick Edwards, Kelly Fullerton, Stephanie M. Kanellopoulou, Nadja Lund, David MacArthur, Daniel G. Mascalzoni, Deborah Shepherd, James Taylor, Patrick L. Terry, Sharon F. Winter, Stefan F. TI From patients to partners: participant-centric initiatives in biomedical research SO NATURE REVIEWS GENETICS LA English DT Article ID CLINICAL INFORMATION AB Advances in computing technology and bioinformatics mean that medical research is increasingly characterized by large international consortia of researchers that are reliant on large data sets and biobanks. These trends raise a number of challenges for obtaining consent, protecting participant privacy concerns and maintaining public trust. Participant-centred initiatives (PCIs) use social media technologies to address these immediate concerns, but they also provide the basis for long-term interactive partnerships. Here, we give an overview of this rapidly moving field by providing an analysis of the different PCI approaches, as well as the benefits and challenges of implementing PCIs. C1 [Kaye, Jane; Kanellopoulou, Nadja] Univ Oxford, Dept Publ Hlth, HeLEX, Oxford OX3 7LF, England. [Curren, Liam] Univ Oxford, Res Serv, Oxford OX1 3ED, England. [Anderson, Nick] Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA. [Edwards, Kelly; Fullerton, Stephanie M.] Univ Washington, Sch Med, Dept Bioeth & Humanities, Seattle, WA 98195 USA. [Lund, David] HW Commun Ltd, Lancaster LA1 4TZ, England. [MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Mascalzoni, Deborah] EURAC Res, Inst Med Genet, I-39100 Bolzano, Italy. [Shepherd, James] Churchill Hosp, NIHR Biomed Res Ctr, Joint Res Off, Oxford OX3 7LJ, England. [Taylor, Patrick L.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Terry, Sharon F.] Genet Alliance, Washington, DC 20008 USA. [Winter, Stefan F.] Hannover Med Sch, Ctr Publ Hlth Care, Inst Epidemiol Social Med & Hlth Care Syst Res, D-30625 Hannover, Germany. RP Kaye, J (reprint author), Univ Oxford, Dept Publ Hlth, HeLEX, Old Rd Campus, Oxford OX3 7LF, England. EM jane.kaye@law.ox.ac.uk OI Fullerton, Stephanie/0000-0002-0938-6048 FU NCRR NIH HHS [UL1 RR025014]; PHS HHS [U33MC07945-04]; Wellcome Trust [096599, 096599/2/11/Z] NR 29 TC 104 Z9 106 U1 3 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD MAY PY 2012 VL 13 IS 5 BP 371 EP 376 DI 10.1038/nrg3218 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 929EZ UT WOS:000303045400013 PM 22473380 ER PT J AU Katon, J Reiber, G Williams, MA Yanez, D Miller, E AF Katon, Jodie Reiber, Gayle Williams, Michelle A. Yanez, David Miller, Edith TI Antenatal haemoglobin A1c and risk of large-for-gestational-age infants in a multi-ethnic cohort of women with gestational diabetes SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE gestational diabetes; Hb A1c; glycaemic control; birthweight ID GLUCOSE-TOLERANCE LEVELS; BIRTH-WEIGHT; FETAL-GROWTH; LATE PREGNANCY; GLYCATED HEMOGLOBIN; METABOLIC SYNDROME; EXPERT COMMITTEE; MATERNAL OBESITY; UNITED-STATES; DCA 2000 AB Gestational diabetes mellitus (GDM) is a risk factor for delivering a large-for-gestational-age (LGA) infant. Haemoglobin A1c (A1C) is an indicator of glycaemic control. The objective of this study was to test whether higher A1C quartile at the time of diagnosis of GDM is associated with increased risk of delivering a LGA or macrosomic infant. Women with singleton pregnancies treated for GDM at a large diabetes and pregnancy programme located in Charlotte, North Carolina, were eligible for inclusion in this retrospective cohort study. Clinical information, including A1C at diagnosis, treatment, prior medical and obstetric history, and birth data were abstracted from medical records. LGA was defined as birthweight > 90th percentile for gestational age and sex and macrosomia as birthweight > 4000 g. Logistic regression was used to analyse the association of A1C at GDM diagnosis with risk of delivering LGA or macrosomic infants. This study included 502 women. Prevalences of LGA and macrosomia were 4% and 6% respectively. After adjustment there was no detectable trend of increased risk for LGA (P for trend = 0.12) or macrosomia (P for trend = 0.20) across increasing quartiles of A1C at GDM diagnosis. A1C at GDM diagnosis may not be linearly associated with LGA or macrosomia, possibly because of the mediating effect of strict glycaemic control in this clinical setting. C1 [Katon, Jodie; Reiber, Gayle; Williams, Michelle A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Reiber, Gayle] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Yanez, David] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Reiber, Gayle] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Miller, Edith] Carolinas Med Ctr, Diabet & Pregnancy Program, Charlotte, NC 28203 USA. RP Katon, J (reprint author), Univ Washington, Dept Epidemiol, Box 357236, Seattle, WA 98195 USA. EM jkaton@u.washington.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH [T32 HD052462]; Achievement Rewards for College Scientists (ARCS); Samuel and Althea Stroum Foundation; University of Washington Department of Epidemiology FX Jodie Katon was supported by grant number T32 HD052462 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH; Achievement Rewards for College Scientists (ARCS); and the Samuel and Althea Stroum Foundation. This study was also funded by a grant from the University of Washington Department of Epidemiology. The authors would like to thank Misty Morris, RN for data collection. NR 48 TC 8 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAY PY 2012 VL 26 IS 3 BP 208 EP 217 DI 10.1111/j.1365-3016.2012.01266.x PG 10 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 921IL UT WOS:000302471200005 PM 22471680 ER PT J AU Caruso, TJ Janik, LS Fuzaylov, G AF Caruso, Thomas J. Janik, Luke S. Fuzaylov, Gennadiy TI Airway management of recovered pediatric patients with severe head and neck burns: a review SO PEDIATRIC ANESTHESIA LA English DT Review DE burns; intubation; airway management; contracture; microstomia; pediatric ID DIFFICULT AIRWAY; FIBEROPTIC INTUBATION; CONTRACTURES; CHILDREN; UNIQUE; FACE AB There are approximately 10 000 pediatric burn survivors in the United States each year, many of whom will present for reconstructive surgery after severe burns in the head and neck (1). These recovered burn victims, who are beyond the acute phase of injury, often have significant scarring and contractures in the face, mouth, nares, neck, and chest, which can make airway management challenging and potentially lead to a cannot intubate, cannot ventilate scenario (2). Although numerous cases have been presented in the literature on this topic (317), there are no comprehensive review articles on the unique challenges of airway management in the recovered pediatric burn patient with distorted airway anatomy. This article aims to provide a comprehensive review of airway management in such patients, focusing on challenges encountered during mask ventilation and tracheal intubation, as well as the role of surgical release of neck contractures to facilitate tracheal intubation. Lessons learned from all reported cases identified in a thorough literature search are incorporated into this review. C1 [Caruso, Thomas J.; Janik, Luke S.; Fuzaylov, Gennadiy] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Shriners Hosp Children,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Caruso, TJ (reprint author), Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Shriners Hosp Children,Massachusetts Gen Hosp, 55 Fruit St,Gray Bigelow 444, Boston, MA 02114 USA. EM tjcaruso@partners.org NR 25 TC 2 Z9 2 U1 2 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD MAY PY 2012 VL 22 IS 5 BP 462 EP 468 DI 10.1111/j.1460-9592.2012.03795.x PG 7 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 922IP UT WOS:000302540900009 PM 22260458 ER PT J AU Xiang, M Yuan, YZ Fan, LY Li, YH Li, AJ Yin, LH Scott, MJ Xiao, GZ Billiar, TR Wilson, MA Fan, J AF Xiang, Meng Yuan, Youzhong Fan, Liyan Li, Yuehua Li, Aijun Yin, Lianhua Scott, Melanie J. Xiao, Guozhi Billiar, Timothy R. Wilson, Mark A. Fan, Jie TI ROLE OF MACROPHAGES IN MOBILIZATION OF HEMATOPOIETIC PROGENITOR CELLS FROM BONE MARROW AFTER HEMORRHAGIC SHOCK SO SHOCK LA English DT Article DE G-CSF; HMGB1; RAGE; innate immune; beta-adrenergic receptor ID COLONY-STIMULATING FACTOR; SYMPATHETIC-NERVOUS-SYSTEM; ENHANCED MOBILIZATION; TISSUE-DAMAGE; CUTTING EDGE; G-CSF; INJURY; HMGB1; SITE; ACTIVATION AB The release of hematopoietic progenitor cells (HPCs) from bone marrow (BM) is under tight homeostatic control. Under stress conditions, HPCs migrate from BM and egress into circulation to participate in immune response, wound repair, or tissue regeneration. Hemorrhagic shock with resuscitation (HS/R), resulting from severe trauma and major surgery, promotes HPC mobilization from BM, which, in turn, affects post-HS immune responses. In this study, we investigated the mechanism of HS/R regulation of HPC mobilization from BM. Using a mouse HS/R model, we demonstrate that the endogenous alarmin molecule high-mobility group box 1 mediates HS/R-induced granulocyte colony-stimulating factor secretion from macrophages (M phi in a RAGE [receptor for advanced glycation end products] signaling-dependent manner. Secreted granulocyte colony-stimulating factor, in turn, induces HPC egress from BM. We also show that activation of beta-adrenergic receptors on M phi by catecholamine mediates the HS/R-induced release of high-mobility group box 1. These data indicate that HS/R, a global ischemia-reperfusion stimulus, regulates HPC mobilization through a series of interacting pathways that include neuroendocrine and innate immune systems, in which M phi play a central role. C1 [Xiang, Meng; Yuan, Youzhong; Li, Yuehua; Scott, Melanie J.; Billiar, Timothy R.; Wilson, Mark A.; Fan, Jie] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Xiang, Meng; Yin, Lianhua] Fudan Univ, Shanghai Med Coll, Dept Physiol & Pathophysiol, Shanghai 200433, Peoples R China. [Fan, Liyan] Univ Pittsburgh, Sch Arts & Sci, Pittsburgh, PA USA. [Li, Aijun] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China. [Xiao, Guozhi] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Dept Surg, Surg Res, Pittsburgh, PA 15240 USA. RP Fan, J (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Dept Surg, Surg Res, Bldg 1,Room 2W109,151L U,Univ Dr C, Pittsburgh, PA 15240 USA. EM jif7@pitt.edu FU National Institutes of Health [R01-HL-079669]; National Institutes of Health Center [P50-GM53789]; VA Merit Award; NSFC [81100047/H0111] FX This work was supported by the National Institutes of Health (grant R01-HL-079669 to J.F. and M. A. W.), National Institutes of Health Center (grant P50-GM53789 to T. R. B. and J.F.), VA Merit Award (to J.F.), and NSFC (grant 81100047/H0111 to M.X). NR 38 TC 9 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD MAY PY 2012 VL 37 IS 5 BP 518 EP 523 DI 10.1097/SHK.0b013e318249b81d PG 6 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 928UB UT WOS:000303010000011 PM 22293600 ER PT J AU Sasaki, Y Nanez, JE Watanabe, T AF Sasaki, Yuka Nanez, Jose E. Watanabe, Takeo TI Recent progress in perceptual learning research SO WILEY INTERDISCIPLINARY REVIEWS-COGNITIVE SCIENCE LA English DT Article ID PRIMARY VISUAL-CORTEX; VERNIER DISCRIMINATION TASK; TOP-DOWN INFLUENCES; TIME-COURSE; TEXTURE-DISCRIMINATION; CONTRAST SENSITIVITY; SPATIAL-FREQUENCY; V1 NEURONS; ORIENTATION; MOTION AB Perceptual learning is defined as long-term improvement in perceptual or sensory systems resulting from repeated practice or experience. As the number of perceptual learning studies has increased, controversies and questions have arisen regarding divergent aspects of perceptual learning, including: (1) stages in which perceptual learning occurs, (2) effects of training type, (3) changes in neural processing during the time course of learning, (4) effects of feedback as to correctness of a subject's responses, and (5) double training. Here we review each of these aspects and suggest fruitful directions for future perceptual learning research. WIREs Cogn Sci 2012, 3:293299. doi: 10.1002/wcs.1175 C1 [Watanabe, Takeo] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Watanabe, Takeo] Boston Univ, Ctr Neurosci, Boston, MA 02215 USA. [Sasaki, Yuka] Harvard Univ, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. [Nanez, Jose E.] Arizona State Univ, Div Social & Behav Sci, New Coll Interdisciplinary Arts & Sci, Glendale, AZ USA. RP Watanabe, T (reprint author), Boston Univ, Dept Psychol, 64 Cummington St, Boston, MA 02215 USA. EM takeo@bu.edu NR 72 TC 4 Z9 4 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5078 EI 1939-5086 J9 WIRES COGN SCI JI Wiley Interdiscip. Rev.-Cogn. Sci. PD MAY-JUN PY 2012 VL 3 IS 3 BP 293 EP 299 DI 10.1002/wcs.1175 PG 7 WC Psychology, Experimental SC Psychology GA 926XW UT WOS:000302867000002 ER PT J AU Yuan, GC AF Yuan, Guo-Cheng TI Linking genome to epigenome SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE LA English DT Article ID EMBRYONIC STEM-CELLS; ENCODED NUCLEOSOME ORGANIZATION; CPG ISLAND METHYLATION; POLYCOMB TARGET GENES; NOVO DNA METHYLATION; SACCHAROMYCES-CEREVISIAE; HISTONE MODIFICATIONS; CHROMATIN-STRUCTURE; HIGH-RESOLUTION; NONCODING RNAS AB Recent epigenomic studies have identified significant differences between developmental stages and cell types. While the importance of epigenetic regulation has been increasingly recognized, it remains unclear how the global epigenetic patterns are established and maintained. Here I review a number of recent studies with the emphasis on the role of the genomic sequence in shaping the epigenetic landscape. These studies strongly suggest that the sequence information is important not just for controlling target specificity but for orchestrating the diversity of epigenetic patterns among different cell types. The epigenome is maintained by the complex network of a large number of interactions. Integrative approaches are needed to gain insights into these networks. WIREs Syst Biol Med 2012. doi: 10.1002/wsbm.1165 C1 [Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Yuan, GC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM gcyuan@jimmy.harvard.edu FU HSPH; NIH [1R01HG005085-01A2] FX I apologize for omission of relevant references due to space restrictions. I thank Drs Franziska Michor and Shirley Liu for helpful discussions. This research was supported by an HSPH Career Incubator Award and the NIH grant 1R01HG005085-01A2. NR 140 TC 12 Z9 12 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1939-5094 J9 WIRES SYST BIOL MED JI Wiley Interdiscip. Rev.-Syst. Biol PD MAY-JUN PY 2012 VL 4 IS 3 BP 297 EP 309 DI 10.1002/wsbm.1165 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 926YA UT WOS:000302867500007 PM 22344857 ER PT J AU Saladin, ME Gray, KM Carpenter, MJ LaRowe, SD DeSantis, SM Upadhyaya, HP AF Saladin, Michael E. Gray, Kevin M. Carpenter, Matthew J. LaRowe, Steven D. DeSantis, Stacia M. Upadhyaya, Himanshu P. TI Gender Differences in Craving and Cue Reactivity to Smoking and Negative Affect/Stress Cues SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID NICOTINE REPLACEMENT THERAPY; LUNG-CANCER RISK; SEX-DIFFERENCES; INDIVIDUAL-DIFFERENCES; CIGARETTE AVAILABILITY; MOOD INDUCTION; MENSTRUAL-CYCLE; FEMALE SMOKERS; DRUG-ABUSE; CESSATION AB There is evidence that women may be less successful when attempting to quit smoking than men. One potential contributory cause of this gender difference is differential craving and stress reactivity to smoking- and negative affect/stress-related cues. The present human laboratory study investigated the effects of gender on reactivity to smoking and negative affect/stress cues by exposing nicotine dependent women (n = 37) and men (n = 53) smokers to two active cue types, each with an associated control cue: (1) in vivo smoking cues and in vivo neutral control cues, and (2) imagery-based negative affect/stress script and a neutral/relaxing control script. Both before and after each cue/script, participants provided subjective reports of smoking-related craving and affective reactions. Heart rate (HR) and skin conductance (SC) responses were also measured. Results indicated that participants reported greater craving and SC in response to smoking versus neutral cues and greater subjective stress in response to the negative affect/stress versus neutral/relaxing script. With respect to gender differences, women evidenced greater craving, stress and arousal ratings and lower valence ratings (greater negative emotion) in response to the negative affect/stressful script. While there were no gender differences in responses to smoking cues, women trended towards higher arousal ratings. Implications of the findings for treatment and tobacco-related morbidity and mortality are discussed. ?(Am J Addict 2012;21:210220) C1 [Saladin, Michael E.] Med Univ S Carolina, Dept Hlth Sci & Res, Coll Hlth Profess, Charleston, SC 29425 USA. [Saladin, Michael E.; Carpenter, Matthew J.; LaRowe, Steven D.; DeSantis, Stacia M.; Upadhyaya, Himanshu P.] Med Univ S Carolina, Clin Neurosci Div, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Gray, Kevin M.] Med Univ S Carolina, Youth Div, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Carpenter, Matthew J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [DeSantis, Stacia M.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [LaRowe, Steven D.] Ralph H Johnson Vet Affairs Med Ctr, Subst Abuse Treatment Ctr, Mental Hlth Serv, Charleston, SC USA. [Upadhyaya, Himanshu P.] Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Saladin, ME (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, Coll Hlth Profess, 77 President St,Room 224,MSC700, Charleston, SC 29425 USA. EM saladinm@musc.edu FU NCATS NIH HHS [UL1 TR000062]; NCRR NIH HHS [UL1 RR029882-01, KL2 RR029880, KL2 RR029880-01, KL2 RR029880-02, KL2 RR029880-03, M01 RR001070, M01 RR01070, TL1 RR029881, TL1 RR029881-01, TL1 RR029881-02, TL1 RR029881-03, UL1 RR029882, UL1 RR029882-02, UL1 RR029882-03]; NIDA NIH HHS [K12 DA000357, K23 DA020482, P50 DA016511, P50 DA016511-01, P50 DA016511-02, P50 DA016511-03, P50 DA016511-04, P50 DA016511-05, P50 DA016511-06, P50 DA016511-07, P50 DA016511-08, P50 DA016511-09, P50 DA016511-10] NR 82 TC 33 Z9 34 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2012 VL 21 IS 3 BP 210 EP 220 DI 10.1111/j.1521-0391.2012.00232.x PG 11 WC Substance Abuse SC Substance Abuse GA 923IL UT WOS:000302612900006 PM 22494223 ER PT J AU Hughes, T Adler, A Merrill, JT Kelly, JA Kaufman, KM Williams, A Langefeld, CD Gilkeson, GS Sanchez, E Martin, J Boackle, SA Stevens, AM Alarcon, GS Niewold, TB Brown, EE Kimberly, RP Edberg, JC Ramsey-Goldman, R Petri, M Reveille, JD Criswell, LA Vila, LM Jacob, CO Gaffney, PM Moser, KL Vyse, TJ Alarcon-Riquelme, ME James, JA Tsao, BP Scofield, RH Harley, JB Richardson, BC Sawalha, AH AF Hughes, Travis Adler, Adam Merrill, Joan T. Kelly, Jennifer A. Kaufman, Kenneth M. Williams, Adrienne Langefeld, Carl D. Gilkeson, Gary S. Sanchez, Elena Martin, Javier Boackle, Susan A. Stevens, Anne M. Alarcon, Graciela S. Niewold, Timothy B. Brown, Elizabeth E. Kimberly, Robert P. Edberg, Jeffrey C. Ramsey-Goldman, Rosalind Petri, Michelle Reveille, John D. Criswell, Lindsey A. Vila, Luis M. Jacob, Chaim O. Gaffney, Patrick M. Moser, Kathy L. Vyse, Timothy J. Alarcon-Riquelme, Marta E. James, Judith A. Tsao, Betty P. Scofield, R. Hal Harley, John B. Richardson, Bruce C. Sawalha, Amr H. CA BIOLUPUS Network TI Analysis of autosomal genes reveals gene-sex interactions and higher total genetic risk in men with systemic lupus erythematosus SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID MULTIFACTOR-DIMENSIONALITY REDUCTION; GENOME-WIDE ASSOCIATION; MULTIPLE-SCLEROSIS; REVISED CRITERIA; SUSCEPTIBILITY; POLYMORPHISMS; CLASSIFICATION; ARCHITECTURE; VARIANTS; DISEASE AB Objectives Systemic lupus erythematosus (SLE) is a sexually dimorphic autoimmune disease which is more common in women, but affected men often experience a more severe disease. The genetic basis of sexual dimorphism in SLE is not clearly defined. A study was undertaken to examine sex-specific genetic effects among SLE susceptibility loci. Methods A total of 18 autosomal genetic susceptibility loci for SLE were genotyped in a large set of patients with SLE and controls of European descent, consisting of 5932 female and 1495 male samples. Sex-specific genetic association analyses were performed. The sex-gene interaction was further validated using parametric and nonparametric methods. Aggregate differences in sex-specific genetic risk were examined by calculating a cumulative genetic risk score for SLE in each individual and comparing the average genetic risk between male and female patients. Results A significantly higher cumulative genetic risk for SLE was observed in men than in women. (P=4.52x10(-8)) A significant sex-gene interaction was seen primarily in the human leucocyte antigen (HLA) region but also in IRF5, whereby men with SLE possess a significantly higher frequency of risk alleles than women. The genetic effect observed in KIAA1542 is specific to women with SLE and does not seem to have a role in men. Conclusions The data indicate that men require a higher cumulative genetic load than women to develop SLE. These observations suggest that sex bias in autoimmunity could be influenced by autosomal genetic susceptibility loci. C1 [Merrill, Joan T.; Kaufman, Kenneth M.; James, Judith A.; Scofield, R. Hal; Sawalha, Amr H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA. [Hughes, Travis; Adler, Adam; Kelly, Jennifer A.; Kaufman, Kenneth M.; Sanchez, Elena; Gaffney, Patrick M.; Moser, Kathy L.; Alarcon-Riquelme, Marta E.; James, Judith A.; Scofield, R. Hal; Sawalha, Amr H.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Merrill, Joan T.] Oklahoma Med Res Fdn, Clin Pharmacol Program, Oklahoma City, OK 73104 USA. [Kaufman, Kenneth M.; Scofield, R. Hal; Sawalha, Amr H.] Med Ctr, US Dept Vet Affairs, Oklahoma City, OK 73104 USA. [Williams, Adrienne; Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Gilkeson, Gary S.] Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. [Martin, Javier] Consejo Super Invest Cient, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain. [Boackle, Susan A.] Univ Colorado Denver, Sch Med, Div Rheumatol, Aurora, CO USA. [Stevens, Anne M.] Univ Washington, Dept Pediat, Div Rheumatol, Seattle, WA 98195 USA. [Stevens, Anne M.] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA. [Alarcon, Graciela S.; Brown, Elizabeth E.; Kimberly, Robert P.; Edberg, Jeffrey C.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Niewold, Timothy B.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Niewold, Timothy B.] Univ Chicago, Gwen Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA. [Ramsey-Goldman, Rosalind] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Petri, Michelle] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Reveille, John D.] Univ Texas Houston Hlth Sci Ctr, Dept Med, Houston, TX USA. [Criswell, Lindsey A.] Univ Calif San Francisco, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 94143 USA. [Vila, Luis M.] Univ Puerto Rico, Dept Med, San Juan, PR 00936 USA. [Jacob, Chaim O.] Univ So Calif, Dept Med, Los Angeles, CA USA. [Vyse, Timothy J.] Kings Coll London, Guys Hosp, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Guys Hosp, Div Mol Med, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Guys Hosp, Div Immunol, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Guys Hosp, Div Infect & Inflammatory Dis, London WC2R 2LS, England. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta Andalucia, Ctr Genom & Oncol Res, Granada, Spain. [Tsao, Betty P.] Univ Calif Los Angeles, Dept Med, Div Rheumatol, Los Angeles, CA 90024 USA. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Div Rheumatol, Cincinnati, OH USA. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Autoimmune Genom Ctr, Cincinnati, OH USA. [Harley, John B.] Med Ctr, US Dept Vet Affairs, Cincinnati, OH USA. [Richardson, Bruce C.] Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA. [Richardson, Bruce C.] Vet Adm Med Ctr, US Dept Vet Affairs, Ann Arbor, MI 48105 USA. RP Sawalha, AH (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Med, 825 NE 13th St,MS 24, Oklahoma City, OK 73104 USA. EM amr-sawalha@omrf.ouhsc.edu RI D'Alfonso, Sandra/K-7295-2014; Witte, Torsten/B-5783-2016; Martin, Javier/B-8141-2008; Sanchez, Elena/B-4140-2017; OI D'Alfonso, Sandra/0000-0002-3983-9925; Sanchez, Elena/0000-0002-7041-5485; Frostegard, Johan/0000-0002-3569-3367; Silva, Berta/0000-0001-6579-5068; Vasconcelos, Carlos/0000-0002-8073-5028; Kimberly, Robert/0000-0002-5330-3086; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154; Niewold, Timothy/0000-0003-3532-6660 FU Lupus Foundation of America; NIH; Arthritis National Research Foundation; American College of Rheumatology/Research and Education Foundation; Lupus Research Institute; Kirkland Scholar awards; Alliance for Lupus Research; US Department of Veterans Affairs; US Department of Defense [PR094002]; European Science Foundation [07-RNP-083]; Swedish Research Council; Instituto de Salud Carlos III [PS09/00129]; European Union; Consejeria de Salud de Andalucia [PI0012] FX This work was made possible by the Lupus Foundation of America, the NIH (R03AI076729, P20RR020143, P20RR015577, P30AR053483, R01AR042460, R37AI024717, R01AI031584, N01AR62277, P50AR048940, P01AI083194, RC1AR058554, U19AI082714, HHSN266200500026C, P30RR031152, P01AR049084, R01AR043274, R01AI063274, K24AR002138, P602AR30692, UL1RR025741, R01DE018209, R01AR043727, UL1RR025005, R01AR043814, K08AI083790, P30DK42086, L30AI071651, UL1RR024999, R01AR044804, M01RR000079, R21AI070304), Arthritis National Research Foundation, American College of Rheumatology/Research and Education Foundation, Lupus Research Institute, Kirkland Scholar awards, Alliance for Lupus Research, US Department of Veterans Affairs, US Department of Defense PR094002, European Science Foundation to the BIOLUPUS network (07-RNP-083), the Swedish Research Council and the Instituto de Salud Carlos III (PS09/00129), cofinanced partly through FEDER funds of the European Union and grant PI0012 from the Consejeria de Salud de Andalucia. NR 31 TC 22 Z9 23 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAY PY 2012 VL 71 IS 5 BP 694 EP 699 DI 10.1136/annrheumdis-2011-200385 PG 6 WC Rheumatology SC Rheumatology GA 923QO UT WOS:000302634000012 PM 22110124 ER PT J AU Forster, S Grimmer, T Miederer, I Henriksen, G Yousefi, BH Graner, P Wester, HJ Forstl, H Kurz, A Dickerson, BC Bartenstein, P Drzezga, A AF Foerster, Stefan Grimmer, Timo Miederer, Isabelle Henriksen, Gjermund Yousefi, Behrooz Hooshyar Graner, Philipp Wester, Hans-Juergen Foerstl, Hans Kurz, Alexander Dickerson, Bradford C. Bartenstein, Peter Drzezga, Alexander TI Regional Expansion of Hypometabolism in Alzheimer's Disease Follows Amyloid Deposition with Temporal Delay SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Alzheimer's disease; amyloid deposition; fluorodeoxyglucose (FDG) positron emission tomography (PET); hypometabolism; longitudinal study; PiB PET ID CEREBRAL GLUCOSE-METABOLISM; PITTSBURGH COMPOUND-B; MILD COGNITIVE IMPAIRMENT; A-BETA; APOLIPOPROTEIN-E; PET IMAGES; DEMENTIA; MEMORY; PROGRESSION; DIAGNOSIS AB Background: Cross-sectional imaging studies suggest that patterns of hypometabolism (measured by [F-18] fluorodeoxyglucose positron emission tomography [FDG-PET]) and amyloid deposition (measured by [C-11] Pittsburgh Compound B [PiB]-PET) in Alzheimer's disease (AD) show some overlap with each other. This indicates that neuronal dysfunction might spread within the anatomical pattern of amyloid deposition. The aim of this study was to examine longitudinal regional patterns of amyloid deposition and hypometabolism in the same population of mild AD subjects and to establish their regional relationship to each other. Methods: Twenty patients with mild AD underwent baseline (BL) and follow-up (FU) examination with [F-18] FDG-PET and [C-11] PiB-PET. Voxel-by-voxel statistical group comparison (SPM5) was performed between patient BL- and FU-PET data as well as between patients and 15 PiB-negative elderly control subjects, who had undergone identical imaging procedures. To obtain objective measures of regional overlap, Dice similarity coefficients (DSC) between the imaging findings were calculated. Results: Compared with elderly control subjects, AD patients showed typical patterns of BL hypometabolism and BL amyloid deposition, with a similarity of 40% (DSC). Amyloid deposition was more extended than hypometabolism at BL and showed only minor changes over time, whereas significant expansion of hypometabolism was observed, almost exclusively within areas already affected by BL amyloid deposition. Thus, increased similarity of FU hypometabolism with BL amyloid deposition was found (DSC: 47%). Conclusions: Longitudinal regional expansion of cerebral hypometabolism, as a measure of neuronal dysfunction in AD, seems to follow the anatomical pattern of amyloid deposition with temporal delay. This indicates that amyloid-based disruption of neuronal integrity might contribute to the regional expansion of neuronal dysfunction. C1 [Foerster, Stefan] Tech Univ Munich, Dept Nucl Med, Nukl Med Klin & Poliklin, D-81675 Munich, Germany. [Grimmer, Timo; Foerstl, Hans; Kurz, Alexander] Tech Univ Munich, Dept Psychiat & Psychotherapy, D-81675 Munich, Germany. [Foerster, Stefan; Bartenstein, Peter] Univ Munich, Dept Nucl Med, Munich, Germany. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Massachusetts Alzheimers Dis Res Ctr, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Forster, S (reprint author), Tech Univ Munich, Dept Nucl Med, Nukl Med Klin & Poliklin, Ismaninger Str 22, D-81675 Munich, Germany. EM stefan.foerster@lrz.tum.de FU Eisai; GE; Janssen-Cilag; Lundbeck; Merz; Novartis; Pfizer; German Research Foundation (Deutsche Forschungsgemeinschaft) [HE 4560/1-2, DR 445/3-1, 445/4-1]; KKF FX We thank Dr. Doug Greve for his help with the DSC script and implementation in MATLAB. HF discloses fees from Eisai, GE, Janssen-Cilag, Lundbeck, Merz, Novartis, and Pfizer. This work was supported in part by the German Research Foundation (Deutsche Forschungsgemeinschaft) (HE 4560/1-2 to GH, DR 445/3-1 and 445/4-1 to AD), and by a KKF-grant for clinical research of the Technische Universitat Munchen (to AD and TG). All other authors report no biomedical financial interests or potential conflicts of interest. NR 43 TC 46 Z9 46 U1 0 U2 8 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 MAY 1 PY 2012 VL 71 IS 9 BP 792 EP 797 DI 10.1016/j.biopsych.2011.04.023 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 925QM UT WOS:000302776000008 PM 21679929 ER PT J AU Lee, AI Campigotto, F Rawn, JD Neuberg, D Kaufman, RM Berliner, N AF Lee, Alfred Ian Campigotto, Federico Rawn, James D. Neuberg, Donna Kaufman, Richard M. Berliner, Nancy TI Clinical significance of coagulation studies in predicting response to activated recombinant Factor VII in cardiac surgery patients SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE Factor VII; cardiology; transfusion medicine; coagulation; bleeding disorders ID BLOOD-LOSS; DOUBLE-BLIND; EFFICACY; THERAPY; SAFETY C1 [Lee, Alfred Ian] Yale Univ, Sch Med, Dept Med, Sect Hematol, New Haven, CT 06510 USA. [Campigotto, Federico; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Rawn, James D.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Neuberg, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Kaufman, Richard M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Berliner, Nancy] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. RP Lee, AI (reprint author), Yale Univ, Sch Med, Dept Med, Sect Hematol, New Haven, CT 06510 USA. EM nberliner@partners.org NR 10 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2012 VL 157 IS 3 BP 397 EP 400 DI 10.1111/j.1365-2141.2011.08992.x PG 4 WC Hematology SC Hematology GA 922HL UT WOS:000302537900018 PM 22224596 ER PT J AU Harmar, AJ Fahrenkrug, J Gozes, I Laburthe, M May, V Pisegna, JR Vaudry, D Vaudry, H Waschek, JA Said, SI AF Harmar, Anthony J. Fahrenkrug, Jan Gozes, Illana Laburthe, Marc May, Victor Pisegna, Joseph R. Vaudry, David Vaudry, Hubert Waschek, James A. Said, Sami I. TI Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR Review 1 SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Review DE accessory proteins; agonists and antagonists; class B GPCR; PAC1 receptor; PACAP; signal transduction; splice variant; VIP; VPAC1 receptor; VPAC2 receptor ID CEREBELLAR GRANULE NEURONS; PACAP TYPE-1 RECEPTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROTEIN-COUPLED RECEPTOR; DIFFERENTIAL SIGNAL-TRANSDUCTION; LONG-TERM POTENTIATION; IN-SITU HYBRIDIZATION; RAT ADRENAL-MEDULLA; INDUCED PHASE-SHIFT; MICE LACKING PACAP AB Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are members of a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, gastric inhibitory peptide (GIP) and growth hormone-releasing hormone (GHRH). VIP and PACAP exert their actions through three GPCRs PAC1, VPAC1 and VPAC2 belonging to class B (also referred to as class II, or secretin receptor-like GPCRs). This family comprises receptors for all peptides structurally related to VIP and PACAP, and also receptors for parathyroid hormone, corticotropin-releasing factor, calcitonin and related peptides. PAC1 receptors are selective for PACAP, whereas VPAC1 and VPAC2 respond to both VIP and PACAP with high affinity. VIP and PACAP play diverse and important roles in the CNS, with functions in the control of circadian rhythms, learning and memory, anxiety and responses to stress and brain injury. Recent genetic studies also implicate the VPAC2 receptor in susceptibility to schizophrenia and the PAC1 receptor in post-traumatic stress disorder. In the periphery, VIP and PACAP play important roles in the control of immunity and inflammation, the control of pancreatic insulin secretion, the release of catecholamines from the adrenal medulla and as co-transmitters in autonomic and sensory neurons. This article, written by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee on receptors for VIP and PACAP, confirms the existing nomenclature for these receptors and reviews our current understanding of their structure, pharmacology and functions and their likely physiological roles in health and disease. More detailed information has been incorporated into newly revised pages in the IUPHAR database (). C1 [Harmar, Anthony J.] Univ Edinburgh, Univ BHF Ctr Cardiovasc Sci, Queens Med Res Inst, Edinburgh EH16 4TJ, Midlothian, Scotland. [Fahrenkrug, Jan] Univ Copenhagen, Dept Clin Biochem, Copenhagen, Denmark. [Gozes, Illana] Tel Aviv Univ, Sackler Sch Med, Ramat Aviv, Israel. [Laburthe, Marc] Univ Paris 07, INSERM U773, Ctr Rech Biomed Bichat Beaujon CRB3, Paris, France. [May, Victor] Univ Vermont, Coll Med, Dept Anat & Neurobiol, Burlington, VT 05405 USA. [Pisegna, Joseph R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Pisegna, Joseph R.] VA Greater Los Angeles Healthcare Syst, Div Gastroenterol, Los Angeles, CA USA. [Vaudry, David] Univ Rouen, European Inst Peptide Res IFRMP23, Mont St Aignan, France. [Waschek, James A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Said, Sami I.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Said, Sami I.] SUNY Stony Brook, Grad Program Pharmacol, Stony Brook, NY 11794 USA. RP Harmar, AJ (reprint author), Univ Edinburgh, Univ BHF Ctr Cardiovasc Sci, Queens Med Res Inst, 47 Little France Crescent, Edinburgh EH16 4TJ, Midlothian, Scotland. EM tony.harmar@ed.ac.uk OI Vaudry, David/0000-0003-3567-7452; Harmar, Anthony/0000-0002-3838-9264 FU IUPHAR; British Pharmacological Society; British Heart Foundation [RE/08/001] FX AJH is supported by IUPHAR, the British Pharmacological Society and the British Heart Foundation Centre of Research Excellence Award (RE/08/001). NR 178 TC 110 Z9 112 U1 1 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1188 EI 1476-5381 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAY PY 2012 VL 166 IS 1 SI SI BP 4 EP 17 DI 10.1111/j.1476-5381.2012.01871.x PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 923FZ UT WOS:000302606200002 PM 22289055 ER PT J AU Stratz, C Amann, M Berg, DD Morrow, DA Neumann, FJ Hochholzer, W AF Stratz, Christian Amann, Michael Berg, David D. Morrow, David A. Neumann, Franz-Josef Hochholzer, Willibald TI Novel Biomarkers in Cardiovascular Disease: Research Tools or Ready for Personalized Medicine? SO CARDIOLOGY IN REVIEW LA English DT Review DE coronary heart disease; heart failure; therapy stratification; risk stratification; personalized medicine ID ACUTE MYOCARDIAL-INFARCTION; GROWTH-DIFFERENTIATION FACTOR-15; ACUTE CORONARY SYNDROMES; C-REACTIVE PROTEIN; CARDIAC TROPONIN-I; ACUTE CHEST-PAIN; CHRONIC HEART-FAILURE; TERMINAL PROVASOPRESSIN COPEPTIN; RISK STRATIFICATION; ARTERY-DISEASE AB In recent years, a wide range of novel biomarkers have been evaluated for different cardiovascular disease states (eg, ischemia, congestion, and physiological stress), and many have shown promising results for the prediction of cardiovascular end points. However, to become useful for clinicians and to allow for personalized medicine, each novel biomarker must fulfill 3 fundamental criteria: (1) it must be easy to measure; (2) it must provide new information; and (3) it must help the clinician to manage patients. Although many biomarkers may be useful for prognostication, very few have been shown to improve the treatment of patients with cardiovascular disease when implemented in a clinical setting. C1 [Stratz, Christian; Amann, Michael; Neumann, Franz-Josef; Hochholzer, Willibald] Herz Zentrum Bad Krozingen, D-79189 Bad Krozingen, Germany. [Berg, David D.; Morrow, David A.; Hochholzer, Willibald] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. RP Hochholzer, W (reprint author), Herz Zentrum Bad Krozingen, Sudring 15, D-79189 Bad Krozingen, Germany. EM willibald.hochholzer@herzzentrum.de FU Roche Diagnostics; Sanofi-Aventis FX Dr. Morrow has received honoraria for educational presentations from CV Therapeutics and Sanofi-Aventis. He has served as a consultant for Beckman Coulter, Critical Diagnostics, CV Therapeutics, Genentech, Menarini, OrthoClinical Diagnostics, Sanofi-Aventis, Schering Plough, and Siemens. Dr. Hochholzer reports research grant support from Roche Diagnostics and consultant fees from Sanofi-Aventis. All other authors declare no conflict of interest. NR 96 TC 6 Z9 6 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1061-5377 J9 CARDIOL REV JI Cardiol. Rev. PD MAY-JUN PY 2012 VL 20 IS 3 BP 111 EP 117 DI 10.1097/CRD.0b013e31824394e1 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 925PE UT WOS:000302772500003 PM 22301714 ER PT J AU Yi, HS Eom, YS Park, IB Lee, S Hong, S Juppner, H Mannstadt, M Lee, S AF Yi, Hyon-Seung Eom, Young Sil Park, Ie Byung Lee, Sangho Hong, Suntaek Jueppner, Harald Mannstadt, Michael Lee, Sihoon TI Identification and characterization of C106R, a novel mutation in the DNA-binding domain of GCMB, in a family with autosomal-dominant hypoparathyroidism SO CLINICAL ENDOCRINOLOGY LA English DT Article ID CALCIUM-SENSING RECEPTOR; CELLS-MISSING-HOMOLOG; PREPROPARATHYROID HORMONE GENE; PARATHYROID-HORMONE; TRANSCRIPTION FACTOR; RECESSIVE HYPOPARATHYROIDISM; SIGNAL PEPTIDE; DROSOPHILA; HYPOCALCEMIA; EXPRESSION AB Overview Glial cells missing B (GCMB) is a transcription factor that is expressed in the parathyroid hormone (PTH)-secreting cells of the parathyroid glands. Several mutations in GCMB have been reported to cause hypoparathyroidism (HP). We identified a family with two individuals in two generations (mother and son), who are affected by autosomal-dominant hypoparathyroidism (AD-HP). A novel heterozygous mutation in exon 2 of GCMB was identified in both affected individuals that changes cysteine at position 106 of the putative DNA-binding domain of GCMB to arginine (C106R). Methods We performed mutational analysis of the genes encoding GCMB, pre-pro PTH, GATA3 and CaSR using polymerase chain reaction (PCR)-amplified genomic DNA. The identified GCMB mutant was characterized by functional studies including nuclear localization, electrophoretic mobility shift assays (EMSA) and luciferase reporter assays, and homology modelling was performed to generate a three-dimensional structural model for the DNA-binding domain of GCMB to predict the structural consequences of the identified mutation. Results The C106R mutant of GCMB failed to interact with the DNA consensus recognition motif, as determined by EMSA. Furthermore, in comparison with wild-type GCMB, the C106R mutant demonstrated reduced transactivation in luciferase reporter assays; however, the mutant GCMB failed to reduce the activity of the wild-type protein. Consistent with the EMSA findings, homology modelling analysis suggested that replacement of cysteine 106 with arginine would interfere with DNA binding. Conclusions We have identified a novel GCMB mutation that may explain AD-HP in our family. However, the exact mechanism by which this heterozygous mutation leads to the disease in the described family remains to be elucidated. C1 [Yi, Hyon-Seung; Eom, Young Sil; Park, Ie Byung; Lee, Sihoon] Gachon Univ, Dept Internal Med, Sch Med, Inchon 405760, South Korea. [Yi, Hyon-Seung; Eom, Young Sil; Park, Ie Byung; Lee, Sihoon] Gachon Univ, Mol Endocrinol Lab, Sch Med, Inchon 405760, South Korea. [Lee, Sangho] Sungkyunkwan Univ, Dept Biol Sci, Suwon, South Korea. [Hong, Suntaek] Gachon Univ Med & Sci, Canc Cell Biol Lab, Lee Gil Ya Canc & Diabet Inst, Inchon, South Korea. [Jueppner, Harald; Mannstadt, Michael] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. RP Lee, S (reprint author), Gachon Univ, Dept Internal Med, Sch Med, 1198 Guwol Dong, Inchon 405760, South Korea. EM shleemd@gachon.ac.kr FU National Research Foundation of Korea; Ministry of Education, Science and Technology, Korea [2010-0005854]; National Institute of Diabetes and Digestive and Kidney Disease; [K08-DK081669-01]; [RO1-46718-10] FX The authors thank all family members for their participation. We thank Professors Ung-il Chung, Jaesang Kim, Hank Kronenberg and Sung-Kil Lim for their special advices and Dr. Byoungho Choi and Ms. Young Mi Kim for their experimental assistance. We also thank Professor Ravinder Goswami for provision of R110W plasmid. This research was supported by the Basic Science Research Programme through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology, Korea [2010-0005854 to S.L.] and grants from the National Institute of Diabetes and Digestive and Kidney Disease [K08-DK081669-01 to M.M. and RO1-46718-10 to H.J.] NR 30 TC 9 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD MAY PY 2012 VL 76 IS 5 BP 625 EP 633 DI 10.1111/j.1365-2265.2011.04256.x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 922FC UT WOS:000302531200004 PM 22066718 ER PT J AU Nguyen, MH Wissel, MC Shields, RK Salomoni, MA Hao, BH Press, EG Shields, RM Cheng, SJ Mitsani, D Vadnerkar, A Silveira, FP Kleiboeker, SB Clancy, CJ AF Nguyen, M. Hong Wissel, Mark C. Shields, Ryan K. Salomoni, Martin A. Hao, Binghua Press, Ellen G. Shields, Ryan M. Cheng, Shaoji Mitsani, Dimitra Vadnerkar, Aniket Silveira, Fernanda P. Kleiboeker, Steven B. Clancy, Cornelius J. TI Performance of Candida Real-time Polymerase Chain Reaction, beta-D-Glucan Assay, and Blood Cultures in the Diagnosis of Invasive Candidiasis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID FUNGAL-INFECTIONS; WHOLE-BLOOD; SPECIES IDENTIFICATION; NEUTROPENIC PATIENTS; PCR; SERUM; DNA; MANNOPROTEINEMIA; LEUKEMIA; ALBICANS AB Background. The sensitivity of blood cultures for diagnosing invasive candidiasis (IC) is poor. Methods. We performed a validated Candida real-time polymerase chain reaction (PCR) and the Fungitell 1,3-beta-D-glucan (BDG) assay on blood samples collected from prospectively identified patients with IC (n = 55) and hospitalized controls (n = 73). Patients with IC had candidemia (n = 17), deep-seated candidiasis (n = 33), or both (n = 5). Controls had mucosal candidiasis (n = 5), Candida colonization (n = 48), or no known Candida colonization (n = 20). Results. PCR using plasma or sera was more sensitive than whole blood for diagnosing IC (P = .008). Plasma or sera PCR was more sensitive than BDG in diagnosing IC (80% vs 56%; P = .03), with comparable specificity (70% vs 73%; P = .31). The tests were similar in diagnosing candidemia (59% vs 68%; P = .77), but PCR was more sensitive for deep-seated candidiasis (89% vs 53%; P = .004). PCR and BDG were more sensitive than blood cultures among patients with deep-seated candidiasis (88% and 62% vs 17%; P = .0005 and .003, respectively). PCR and culture identified the same Candida species in 82% of patients. The sensitivity of blood cultures combined with PCR or BDG among patients with IC was 98% and 79%, respectively. Conclusions. Candida PCR and, to a lesser extent, BDG testing significantly enhanced the ability of blood cultures to diagnose IC. C1 [Nguyen, M. Hong; Shields, Ryan K.; Hao, Binghua; Press, Ellen G.; Cheng, Shaoji; Mitsani, Dimitra; Vadnerkar, Aniket; Silveira, Fernanda P.; Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. [Wissel, Mark C.; Salomoni, Martin A.; Shields, Ryan M.; Kleiboeker, Steven B.] Viracor IBT Labs, Lees Summit, MO USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. RP Nguyen, MH (reprint author), Univ Pittsburgh, Dept Med, 3550 Terrace St,Suite 871, Pittsburgh, PA 15261 USA. EM mhn5@pitt.edu FU Viracor-IBT Laboratories; Pfizer; Merck; CSL Behring; Biotherapies for Life; AstraZeneca FX This work was supported by an investigator-initiated research grant from Viracor-IBT Laboratories (to M. H. N.).; M. C. W., M. A. S., R. M. S., and S. B. K. are employees of Viracor-IBT Laboratories. M. H. N. has received research funding from Viracor-IBT Laboratories and grant support from Pfizer, Merck, CSL Behring, and Biotherapies for Life. F. P. S. has received research funding from Pfizer and CSL Behring. C. J. C. has received research funding from Pfizer, Merck, and AstraZeneca. R. K. S. has received funding from Pfizer and Merck. All other authors: no conflicts. NR 31 TC 91 Z9 93 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2012 VL 54 IS 9 BP 1240 EP 1248 DI 10.1093/cid/cis200 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 926BG UT WOS:000302805700008 PM 22431804 ER PT J AU Kourkoumpetis, TK Fuchs, BB Coleman, JJ Desalermos, A Mylonakis, E AF Kourkoumpetis, Themistoklis K. Fuchs, Beth Burgwyn Coleman, Jeffrey J. Desalermos, Athanasios Mylonakis, Eleftherios TI Polymerase Chain Reaction-Based Assays for the Diagnosis of Invasive Fungal Infections SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID REAL-TIME PCR; GALACTOMANNAN ENZYME-IMMUNOASSAY; SEQUENCE-BASED AMPLIFICATION; LINKED-IMMUNOSORBENT-ASSAY; STEM-CELL TRANSPLANTS; BETA-D-GLUCAN; BLOOD CULTURE; ASPERGILLUS-FUMIGATUS; CANDIDA-ALBICANS; CLINICAL-SAMPLES AB Traditional laboratory techniques are unable to provide rapid and efficient diagnosis of fungal infections. We discuss the usefulness of emerging polymerase chain reaction-based assays, which are a promising means for improvement of diagnosis, permitting initiation of rapid and targeted antifungal treatment.Currently accepted fungal diagnostic techniques, such as culture, biopsy, and serology, lack rapidity and efficiency. Newer diagnostic methods, such as polymerase chain reaction (PCR)-based assays, have the potential to improve fungal diagnostics in a faster, more sensitive, and specific manner. Preliminary data indicate that, when PCR-based fungal diagnostic assays guide antifungal therapy, they may lower patient mortality and decrease unnecessary antifungal treatment, improving treatment-associated costs and avoiding toxicity. Moreover, newer PCR techniques can identify antifungal resistance DNA loci, but the clinical correlation between those loci and clinical failure has to be studied further. In addition, future studies need to focus on the implementation of PCR techniques in clinical decision making and on combining them with other diagnostic tests. A consensus on the standardization of PCR techniques, along with validation from large prospective studies, is necessary to allow widespread adoption of these assays. C1 [Kourkoumpetis, Themistoklis K.; Fuchs, Beth Burgwyn; Coleman, Jeffrey J.; Desalermos, Athanasios; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis,Dept Med, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis,Dept Med, 55 Fruit St,Gray Jackson 504, Boston, MA 02114 USA. EM emylonakis@partners.org RI Coleman, Jeffrey/E-2981-2015; OI Coleman, Jeffrey/0000-0001-8579-1996 FU Astellas; T2 Biosystems FX E. M. has received grant support from Astellas and T2 Biosystems for projects irrelevant to this work and has served in Advisory Board for Astellas. All other authors report no potential conflicts. NR 85 TC 21 Z9 23 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2012 VL 54 IS 9 BP 1322 EP 1331 DI 10.1093/cid/cis132 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 926BG UT WOS:000302805700018 PM 22362884 ER PT J AU Farris, AB Colvin, RB AF Farris, Alton B. Colvin, Robert B. TI Renal interstitial fibrosis: mechanisms and evaluation SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE epithelial/mesenchymal transition; kidney/renal fibrosis; morphometry; myofibroblast ID EPITHELIAL-MESENCHYMAL TRANSITION; CHRONIC KIDNEY-DISEASE; UNILATERAL URETERAL OBSTRUCTION; ENDOPLASMIC-RETICULUM STRESS; CHRONIC ALLOGRAFT NEPHROPATHY; HEPATOCYTE GROWTH-FACTOR; CD4(+) T-CELLS; COMPUTERIZED IMAGE-ANALYSIS; PROXIMAL TUBULAR CELLS; E-CADHERIN EXPRESSION AB Purpose of review Tubulointerstitial injury in the kidney is complex, involving a number of independent and overlapping cellular and molecular pathways, with renal interstitial fibrosis and tubular atrophy (IFTA) as the final common pathway. Furthermore, there are multiple ways to assess IFTA. Recent findings Cells involved include tubular epithelial cells, fibroblasts, fibrocytes, myofibroblasts, monocyte/macrophages, and mast cells with complex and still incompletely characterized cell-molecular interactions. Molecular mediators involved are numerous and involve pathways such as transforming growth factor (TGF)-beta, bone morphogenic protein (BMP), platelet-derived growth factor (PDGF), and hepatocyte growth factor (HGF). Recent genomic approaches have shed insight into some of these cellular and molecular pathways. Pathologic evaluation of IFTA is central in assessing the severity of chronic disease; however, there are a variety of methods used to assess IFTA. Most assessment of IFTA relies on pathologist assessment of special stains such as trichrome, Sirius Red, and collagen III immunohistochemistry. Visual pathologist assessment can be prone to intra and interobserver variability, but some methods employ computerized morphometery, without a clear consensus as to the best method. Summary IFTA results from on orchestration of cell types and molecular pathways. Opinions vary on the optimal qualitative and quantitative assessment of IFTA. C1 [Farris, Alton B.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Colvin, Robert B.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Colvin, Robert B.] Harvard Univ, Sch Med, Boston, MA USA. RP Farris, AB (reprint author), Emory Univ Hosp, 1364 Clifton Rd NE,Room H-188, Atlanta, GA 30322 USA. EM abfarri@emory.edu FU National Institutes of Health [U01-AI-63623, U01-AI-077816, U01-AI-070107] FX Prior work by the authors related to this publication has been supported by grants from the National Institutes of Health (U01-AI-63623, U01-AI-077816, U01-AI-070107). NR 230 TC 83 Z9 95 U1 3 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 2012 VL 21 IS 3 BP 289 EP 300 DI 10.1097/MNH.0b013e3283521cfa PG 12 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 925OA UT WOS:000302769500009 PM 22449945 ER PT J AU Weekley, CC Peralta, CA AF Weekley, Cristin C. Peralta, Carmen A. TI Advances in the use of multimarker panels for renal risk stratification SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE albuminuria; chronic kidney disease; creatinine; cystatin C; multimarker ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; CYSTATIN-C; CARDIOVASCULAR EVENTS; ADVERSE OUTCOMES; SERUM CREATININE; ASSOCIATION; RECLASSIFICATION; PROTEINURIA; CKD AB Purpose of review This review discusses novel studies in the past year that have examined the use of combinations of multiple markers to improve risk prediction in the setting of chronic kidney disease (CKD). We will focus on multimarker panels to: improve prediction of CKD onset; improve classification of CKD and risk stratification of persons with CKD; and develop individual-level risk scores for progression to end-stage renal disease (ESRD). Recent findings One study reported that several novel circulation biomarkers may aid in predicting incident CKD and microalbuminuria. Second, our group has shown that the combination of creatinine, cystatin C, and albuminuria improves detection and risk stratification for death, heart failure, cardiovascular events, and ESRD compared with creatinine alone. Finally, a highly accurate individual risk score was developed to predict progression to ESRD using readily available clinical markers. Summary The combination of multiple markers improves detection and risk stratification in CKD. Future research is needed in understanding the use of a 'renal panel' for detection, classification, and risk stratification in kidney disease in diverse populations. The studies presented here represent the beginning of a paradigm shift to multimarker panels in nephrology. C1 [Weekley, Cristin C.; Peralta, Carmen A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Weekley, Cristin C.; Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Peralta, CA (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM carmenalicia.peralta@ucsf.edu FU National Institutes of Diabetes and Digestive and Kidney Diseases [1K23SK082793-01]; Robert Wood Johnson Harold Amos award FX C.A.P. is funded by the National Institutes of Diabetes and Digestive and Kidney Diseases (1K23SK082793-01) and a Robert Wood Johnson Harold Amos award. NR 32 TC 3 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 2012 VL 21 IS 3 BP 301 EP 308 DI 10.1097/MNH.0b013e328352132d PG 8 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 925OA UT WOS:000302769500010 PM 22449944 ER PT J AU Richardson, PG Laubach, JP Schlossman, RL Ghobrial, IM Redman, KC Mckenney, M Warren, D Noonan, K Lunde, L Doss, D Colson, K Hideshima, T Mitsiades, C Munshi, NC Anderson, KC AF Richardson, Paul G. Laubach, Jacob P. Schlossman, Robert L. Ghobrial, Irene M. Redman, Katherine C. Mckenney, Mary Warren, Diane Noonan, Kimberly Lunde, Laura Doss, Deborah Colson, Kathleen Hideshima, Teru Mitsiades, Constantine Munshi, Nikhil C. Anderson, Kenneth C. TI The potential benefits of participating in early-phase clinical trials in multiple myeloma: long-term remission in a patient with relapsed multiple myeloma treated with 90 cycles of lenalidomide and bortezomib SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE bortezomib; lenalidomide; long-term treatment; multiple myeloma; relapse ID PLUS DEXAMETHASONE; THERAPY; COMBINATION; THALIDOMIDE; ANALOGS; CELLS AB We present the case of a woman with relapsed multiple myeloma (MM) who received combination lenalidomide and bortezomib therapy for 90 cycles followed by continuous lenalidomide monotherapy and has completed over 100 cycles of treatment to date. The patient was diagnosed with advanced-stage, symptomatic MM in 2001. Following a partial response (PR) to dexamethasone in combination with pamidronate and thalidomide, the patient underwent protocol-directed non-myeloablative allogeneic bone marrow transplantation from her matched sibling donor the following year. In 2004, the patient relapsed and was enrolled in a phase I, dose-escalation trial of lenalidomide plus bortezomib for relapsed and refractory MM. After eight cycles of study treatment, the patient achieved a minimal response. The patient received a total of 90 cycles of treatment with lenalidomide 5 mg given for 14 d every 21 d, and 1 mg/m2 of bortezomib initially given on days 1, 4, 8, and 11 for the first 20 cycles, and then weekly thereafter on days 1 and 8. Bortezomib was discontinued after 90 cycles, and the patient continued to receive lenalidomide monotherapy. As of cycle 100, the patient achieved a PR. Currently, she is clinically stable with response sustained for over 7 yrs. Therapy has been well tolerated with no significant long-term toxicity; no dose reductions of lenalidomide and bortezomib were required. The excellent tolerability of this steroid-free approach and the durable response seen underscore the potential benefits of participating in early-phase clinical trials evaluating novel therapies and new drug combinations. This case further supports that combination treatment with lenalidomide and bortezomib is an effective therapy in the management of patients with relapsed and refractory MM. C1 [Richardson, Paul G.; Laubach, Jacob P.; Schlossman, Robert L.; Ghobrial, Irene M.; Redman, Katherine C.; Mckenney, Mary; Warren, Diane; Noonan, Kimberly; Lunde, Laura; Doss, Deborah; Colson, Kathleen; Hideshima, Teru; Mitsiades, Constantine; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Munshi, Nikhil C.] Boston VA Healthcare Syst, Boston, MA USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St,Suite D1B30, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu FU Celgene Corporation; Millennium Pharmaceuticals; Novartis FX The authors received editorial support from Excerpta Medica in the preparation of this manuscript, funded by Celgene Corporation. The authors were fully responsible for content and editorial decisions for this manuscript.; Paul G. Richardson is a member of Advisory Board, Millennium Pharmaceuticals, Celgene Corporation Corporation, Novartis, Johnson & Johnson; Irene M. Ghobrial is a member of Advisory Board, Celgene Corporation, Millennium Pharmaceuticals, Novartis; Teru Hideshima is a Consultant for Acetylon Pharmaceuticals; Constantine Mitsiades is a member of Advisory Board, Millennium Pharmaceuticals, Novartis, Merck; Nikhil C. Munshi is a Consultant for Celgene Corporation, Millennium Pharmaceuticals, Novartis; Kenneth C. Anderson is a member of Advisory Board, Millennium Pharmaceuticals, Celgene Corporation, Novartis, Merck; and has received funding from Millennium Pharmaceuticals, Celgene Corporation, Novartis; He is also a founder of Acetylon Pharmaceuticals. All other authors state that they have no conflicts of interest. NR 18 TC 8 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD MAY PY 2012 VL 88 IS 5 BP 446 EP 449 DI 10.1111/j.1600-0609.2012.01765.x PG 4 WC Hematology SC Hematology GA 923IE UT WOS:000302612200010 PM 22300348 ER PT J AU Klepac-Ceraj, V Hayes, CA Gilhooly, WP Lyons, TW Kolter, R Pearson, A AF Klepac-Ceraj, V. Hayes, C. A. Gilhooly, W. P. Lyons, T. W. Kolter, R. Pearson, A. TI Microbial diversity under extreme euxinia: Mahoney Lake, Canada SO GEOBIOLOGY LA English DT Review ID PURPLE SULFUR BACTERIA; MEROMICTIC SALT LAKE; RIBOSOMAL DATABASE PROJECT; SULFATE-REDUCING BACTERIA; COMPLETE GENOME SEQUENCE; HALOPHILUS SP-NOV.; IN-SITU ANALYSIS; CADAGNO SWITZERLAND; SULFUROSPIRILLUM-DELEYIANUM; MESOPHILIC CRENARCHAEOTA AB Mahoney Lake, British Columbia, Canada, is a stratified, 15-m deep saline lake with a euxinic (anoxic, sulfidic) hypolimnion. A dense plate of phototrophic purple sulfur bacteria is found at the chemocline, but to date the rest of the Mahoney Lake microbial ecosystem has been underexamined. In particular, the microbial community that resides in the aphotic hypolimnion and/or in the lake sediments is unknown, and it is unclear whether the sulfate reducers that supply sulfide for phototrophy live only within, or also below, the plate. Here we profiled distributions of 16S rRNA genes using gene clone libraries and PhyloChip microarrays. Both approaches suggest that microbial diversity is greatest in the hypolimnion (8 m) and sediments. Diversity is lowest in the photosynthetic plate (7 m). Shallower depths (5 m, 7 m) are rich in Actinobacteria, Alphaproteobacteria, and Gammaproteobacteria, while deeper depths (8 m, sediments) are rich in Crenarchaeota, Natronoanaerobium, and Verrucomicrobia. The heterogeneous distribution of Deltaproteobacteria and Epsilonproteobacteria between 7 and 8 m is consistent with metabolisms involving sulfur intermediates in the chemocline, but complete sulfate reduction in the hypolimnion. Overall, the results are consistent with the presence of distinct microbial niches and suggest zonation of sulfur cycle processes in this stratified system. C1 [Klepac-Ceraj, V.] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Klepac-Ceraj, V.; Kolter, R.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Hayes, C. A.; Pearson, A.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA. [Gilhooly, W. P.] Washington Univ, Dept Earth & Planetary Sci, St Louis, MO 63130 USA. [Lyons, T. W.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA. RP Klepac-Ceraj, V (reprint author), Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. EM vanjakle@gmail.com; pearson@eps.harvard.edu OI Klepac-Ceraj, Vanja/0000-0001-5387-5706; Gilhooly, William/0000-0002-5931-5571 FU The David and Lucille Packard Foundation; NSF Chemical Oceanography (AP); NASA; ACS Petroleum Research Fund FX We thank Chris Reinhard, Noah Planavsky, Ben Gill and Anthony Chappaz for their help with sample collection and other aspects of the fieldwork; Eoin Brodie and Yvette Piceno for their help with the PhyloChip setup, and Harvard University's LS100r students for their help with the data analyses. We thank the editors at Geobiology and three excellent reviewers for their feedback. This work was supported by The David and Lucille Packard Foundation and by NSF Chemical Oceanography (AP) and the NASA Exobiology Program and the ACS Petroleum Research Fund (WG and TL). NR 101 TC 18 Z9 19 U1 3 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1472-4677 J9 GEOBIOLOGY JI Geobiology PD MAY PY 2012 VL 10 IS 3 SI SI BP 223 EP 235 DI 10.1111/j.1472-4669.2012.00317.x PG 13 WC Biology; Environmental Sciences; Geosciences, Multidisciplinary SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Geology GA 920IM UT WOS:000302397500005 PM 22329601 ER PT J AU Pham, LDD Hayakawa, K Seo, JH Nguyen, MN Som, AT Lee, BJ Guo, SZ Kim, KW Lo, EH Arai, K AF Pham, Loc-Duyen D. Hayakawa, Kazuhide Seo, Ji Hae Minh-Nguyet Nguyen Som, Angel T. Lee, Brian J. Guo, Shuzhen Kim, Kyu-Won Lo, Eng H. Arai, Ken TI Crosstalk between oligodendrocytes and cerebral endothelium contributes to vascular remodeling after white matter injury SO GLIA LA English DT Article DE oligodendrocyte; white matter injury; matrix metalloproteinase-9; vascular remodeling; cerebral endothelial cell ID MATRIX-METALLOPROTEINASE; PRECURSOR CELLS; BRAIN-INJURY; NEURAL PROGENITORS; ISCHEMIC BRAIN; STROKE; ASTROCYTES; MECHANISMS; REPAIR; MATRIX-METALLOPROTEINASE-9 AB After stroke and brain injury, cortical gray matter recovery involves mechanisms of neurovascular matrix remodeling. In white matter, however, the mechanisms of recovery remain unclear. In this study, we demonstrate that oligodendrocytes secrete matrix metalloproteinase-9 (MMP-9), which accelerates the angiogenic response after white matter injury. In primary oligodendrocyte cultures, treatment with the proinflammatory cytokine interleukin-1 beta (IL-1 beta) induced an upregulation and secretion of MMP-9. Conditioned media from IL-1 beta-stimulated oligodendrocytes significantly amplified matrigel tube formation in brain endothelial cells, indicating that MMP-9 from oligodendrocytes can promote angiogenesis in vitro. Next, we asked whether similar signals and substrates operate after white matter injury in vivo. Focal white matter injury and demyelination was induced in mice via stereotactic injection of lysophosphatidylcholine into corpus callosum. Western blot analysis showed that IL-1 beta expression was increased in damaged white matter. Immunostaining demonstrated MMP-9 signals in myelin-associated oligodendrocytic basic protein-positive oligodendrocytes. Treatment with an IL-1 beta-neutralizing antibody suppressed the MMP-9 response in oligodendrocytes. Finally, we confirmed that the broad spectrum MMP inhibitor GM6001 inhibited angiogenesis around the injury area in this white matter injury model. In gray matter, a neurovascular niche promotes cortical recovery after brain injury. Our study suggests that an analogous oligovascular niche may mediate recovery in white matter. (c) 2012 Wiley Periodicals, Inc. C1 [Pham, Loc-Duyen D.; Hayakawa, Kazuhide; Seo, Ji Hae; Minh-Nguyet Nguyen; Som, Angel T.; Lee, Brian J.; Guo, Shuzhen; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Pham, Loc-Duyen D.; Hayakawa, Kazuhide; Seo, Ji Hae; Minh-Nguyet Nguyen; Som, Angel T.; Lee, Brian J.; Guo, Shuzhen; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Pham, Loc-Duyen D.; Hayakawa, Kazuhide; Seo, Ji Hae; Minh-Nguyet Nguyen; Som, Angel T.; Lee, Brian J.; Guo, Shuzhen; Lo, Eng H.; Arai, Ken] Harvard Univ, Sch Med, Boston, MA USA. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, NeuroVasc Coordinat Res Ctr, Coll Pharm, Seoul, South Korea. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul, South Korea. [Kim, Kyu-Won] Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul, South Korea. RP Arai, K (reprint author), Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. EM karai@partners.org FU Deane Foundation; MGH ECOR; American Heart Association; National Institutes of Health; Japan Society for the Promotion of Science; National Research Foundation of Korea; World Class University; Global Research Laboratory; Creative Research Initiative Program FX Grant sponsors: Deane Foundation, MGH ECOR Fund for Medical Discovery, American Heart Association, National Institutes of Health, Research Abroad from the Japan Society for the Promotion of Science, National Research Foundation of Korea, the World Class University Program, the Global Research Laboratory Program, and the Creative Research Initiative Program. NR 35 TC 35 Z9 38 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-1491 J9 GLIA JI Glia PD MAY PY 2012 VL 60 IS 6 BP 875 EP 881 DI 10.1002/glia.22320 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 923MW UT WOS:000302624400004 PM 22392631 ER PT J AU Fu, HJ Liu, B Frost, JL Hong, SY Jin, M Ostaszewski, B Shankar, GM Costantino, IM Carroll, MC Mayadas, TN Lemere, CA AF Fu, Hongjun Liu, Bin Frost, Jeffrey L. Hong, Soyon Jin, Ming Ostaszewski, Beth Shankar, Ganesh M. Costantino, Isabel M. Carroll, Michael C. Mayadas, Tanya N. Lemere, Cynthia A. TI Complement component C3 and complement receptor type 3 contribute to the phagocytosis and clearance of fibrillar A beta by microglia SO GLIA LA English DT Article DE microglia; A ss; complement component C3; complement receptor type 3; Mac-1; phagocytosis ID CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; AMYLOID FIBRILS; SCAVENGER RECEPTOR; TRANSGENIC MICE; MOUSE MODEL; PEPTIDE; ACTIVATION; NEURODEGENERATION; PROTEIN AB Complement components and their receptors are found within and around amyloid beta (A beta) cerebral plaques in Alzheimer's disease (AD). Microglia defend against pathogens through phagocytosis via complement component C3 and/or engagement of C3 cleavage product iC3b with complement receptor type 3 (CR3, Mac-1). Here, we provide direct evidence that C3 and Mac-1 mediate, in part, phagocytosis and clearance of fibrillar amyloid-beta (fA beta) by murine microglia in vitro and in vivo. Microglia took up not only synthetic fA beta 42 but also amyloid cores from patients with AD, transporting them to lysosomes in vitro. Fibrillar A beta 42 uptake was significantly attenuated by the deficiency or knockdown of C3 or Mac-1 and scavenger receptor class A ligands. In addition, C3 or Mac-1 knockdown combined with a scavenger receptor ligand, fucoidan, further attenuated fibrillar A beta 42 uptake by N9 microglia. Fluorescent fibrillar A beta 42 microinjected cortically was significantly higher in C3 and Mac-1 knockout mice compared with wild-type mice 5 days after surgery, indicating reduced clearance in vivo. Together, these results demonstrate that C3 and Mac-1 are involved in phagocytosis and clearance of fA beta by microglia, providing support for a potential beneficial role for microglia and the complement system in AD pathogenesis. (c) 2012 Wiley Periodicals, Inc. C1 [Fu, Hongjun; Liu, Bin; Frost, Jeffrey L.; Hong, Soyon; Jin, Ming; Ostaszewski, Beth; Shankar, Ganesh M.; Costantino, Isabel M.; Lemere, Cynthia A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Carroll, Michael C.] Harvard Univ, Dept Pediat, Immune Dis Inst, Sch Med, Boston, MA 02115 USA. [Mayadas, Tanya N.] Harvard Univ, Dept Pathol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Lemere, CA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, NRB 636F,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM clemere@rics.bwh.harvard.edu FU National Institutes of Health [AG20159]; NICHD FX Grant sponsor: National Institutes of Health; Grant number: AG20159.; The authors are grateful to Dr. Dennis J. Selkoe for his helpful discussions during this study. N9 microglial cells were obtained from Dr. Joseph El Khoury with the permission of Dr. Paola Ricciardi-Castagnoli. The 1D4B monoclonal antibody developed by Dr. J Thomas August was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA 52242. They also thank Deneen Kozoriz for her help in flow cytometry experiments. NR 43 TC 30 Z9 32 U1 1 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-1491 J9 GLIA JI Glia PD MAY PY 2012 VL 60 IS 6 BP 993 EP 1003 DI 10.1002/glia.22331 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 923MW UT WOS:000302624400013 PM 22438044 ER PT J AU Truman, JP Al Gadban, MM Smith, KJ Jenkins, RW Mayroo, N Virella, G Lopes-Virella, MF Bielawska, A Hannun, YA Hammad, SM AF Truman, Jean-Philip Al Gadban, Mohammed M. Smith, Kent J. Jenkins, Russell W. Mayroo, Nalini Virella, Gabriel Lopes-Virella, Maria F. Bielawska, Alicja Hannun, Yusuf A. Hammad, Samar M. TI Differential regulation of acid sphingomyelinase in macrophages stimulated with oxidized low-density lipoprotein (LDL) and oxidized LDL immune complexes: role in phagocytosis and cytokine release SO IMMUNOLOGY LA English DT Article DE acid sphingomyelinase; HSP70; interleukin-1; oxidized low-density lipoprotein immune complexes ID RECEPTOR-RELATED PROTEIN; RICH MEMBRANE RAFTS; MONOCYTE-DERIVED MACROPHAGES; SECRETORY SPHINGOMYELINASE; CELL-SURFACE; CERAMIDE; DISEASE; GENE; ATHEROGENESIS; CHOLESTEROL AB Oxidized low-density lipoprotein (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) contribute to the formation of lipid-laden macrophages (foam cells). Fc? receptors mediate uptake of oxLDL-IC, whereas scavenger receptors internalize oxLDL. We have previously reported that oxLDL-IC, but not free oxLDL, activate macrophages and prolong their survival. Sphingomyelin is a major constituent of cell membranes and lipoprotein particles and acid sphingomyelinase (ASMase) hydrolyses sphingomyelin to generate the bioactive lipid ceramide. ASMase exists in two forms: lysosomal (L-ASMase) and secretory (S-ASMase). In this study we examined whether oxLDL and oxLDL-IC regulate ASMase differently, and whether ASMase mediates monocyte/macrophage activation and cytokine release. The oxLDL-IC, but not oxLDL, induced early and consistent release of catalytically active S-ASMase. The oxLDL-IC also consistently stimulated L-ASMase activity, whereas oxLDL induced a rapid transient increase in L-ASMase activity before it steadily declined below baseline. Prolonged exposure to oxLDL increased L-ASMase activity; however, activity remained significantly lower than that induced by oxLDL-IC. Further studies were aimed at defining the function of the activated ASMase. In response to oxLDL-IC, heat-shock protein 70B (HSP70B) was up-regulated and localized with redistributed ASMase in the endosomal compartment outside the lysosome. Treatment with oxLDL-IC induced the formation and release of HSP70-containing and IL-1 beta-containing exosomes via an ASMase-dependent mechanism. Taken together, the results suggest that oxLDL and oxLDL-IC differentially regulate ASMase activity, and the pro-inflammatory responses to oxLDL-IC are mediated by prolonged activation of ASMase. These findings may contribute to increased understanding of mechanisms mediating macrophage involvement in atherosclerosis. C1 [Truman, Jean-Philip; Al Gadban, Mohammed M.; Smith, Kent J.; Hammad, Samar M.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Jenkins, Russell W.; Mayroo, Nalini; Bielawska, Alicja; Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.] Med Univ S Carolina, Div Endocrinol, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Hammad, SM (reprint author), Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. EM hammadsm@musc.edu FU National Institutes of Health (NIH) [HL079274, R01 HL079274-04S1]; South Carolina COBRE in Lipidomics and Pathobiology, NCRR [P20 RR17677]; Department of Veterans Affairs; NIH [P20 RR17677]; [P01 HL55782]; [R01 DK081352]; [R01 DK081352-02S1] FX This work was supported by the National Institutes of Health (NIH) grants HL079274, R01 HL079274-04S1 (American Recovery and Investment Act (ARRA)) and the South Carolina COBRE in Lipidomics and Pathobiology (P20 RR17677 from NCRR) to SMH, and P01 HL55782, R01 DK081352, and R01 DK081352-02S1 (ARRA) to MFL-V. This work was also supported by funding from the Department of Veterans Affairs to MFL-V. ASMase KO and ASMase wild-type mice were provided by SC COBRE Animal Pathobiology Core supported by NIH grant P20 RR17677. Special thanks to the Lipidomics Shared Resource facility at MUSC. We thank Dr Richard Kolesnick (Memorial Sloan-Kettering Cancer Center, New York) for anti-ASMase antibodies and Charlyne Chassereau (MUSC) for assistance with lipoprotein isolation. NR 67 TC 18 Z9 19 U1 0 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAY PY 2012 VL 136 IS 1 BP 30 EP 45 DI 10.1111/j.1365-2567.2012.03552.x PG 16 WC Immunology SC Immunology GA 920JA UT WOS:000302399200005 PM 22236141 ER PT J AU Stanton, RC AF Stanton, Robert C. TI Glucose-6-phosphate dehydrogenase, NADPH, and cell survival SO IUBMB LIFE LA English DT Review DE antioxidants; nitric oxide; reactive oxygen species; signaling; oxidative stress ID PENTOSE-PHOSPHATE PATHWAY; GLUCOSE INHIBITS GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; OXIDATIVE STRESS; OXIDANT STRESS; SUPEROXIDE-PRODUCTION; ENZYME DEFICIENCY; DIABETES-MELLITUS; ENDOTHELIAL-CELLS; GROWTH; RAT AB Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway. Many scientists think that the roles and regulation of G6PD in physiology and pathophysiology have been well established as the enzyme was first identified 80 years ago. And that G6PD has been extensively studied especially with respect to G6PD deficiency and its association with hemolysis, and with respect to the role G6PD plays in lipid metabolism. But there has been a growing understanding of the central importance of G6PD to cellular physiology as it is a major source of NADPH that is required by many essential cellular systems including the antioxidant pathways, nitric oxide synthase, NADPH oxidase, cytochrome p450 system, and others. Indeed G6PD is essential for cell survival. It has also become evident that G6PD is highly regulated by many signals that affect transcription, post-translation, intracellular location, and interactions with other protein. Pathophysiologic roles for G6PD have also been identified in such disease processes as diabetes, aldosterone-induced endothelial dysfunction, cancer, and others. It is now clear that G6PD is under complex regulatory control and of central importance to many cellular processes. In this review the biochemistry, regulatory signals, physiologic roles, and pathophysiologic roles for G6PD that have been elucidated over the past 20 years are discussed. 2012 IUBMB IUBMB Life, 2012 C1 [Stanton, Robert C.] Joslin Diabet Ctr, Renal Sect, Boston, MA 02215 USA. [Stanton, Robert C.] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Stanton, Robert C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Stanton, RC (reprint author), Joslin Diabet Ctr, Renal Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM robert.stanton@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK054380, R01 DK054380-08] NR 57 TC 101 Z9 104 U1 3 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1521-6543 EI 1521-6551 J9 IUBMB LIFE JI IUBMB Life PD MAY PY 2012 VL 64 IS 5 BP 362 EP 369 DI 10.1002/iub.1017 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 924WA UT WOS:000302720800002 PM 22431005 ER PT J AU Ho, TT Cadena, J Childs, LM Gonzalez-Velez, M Lewis, JS AF Ho, Tony T. Cadena, Jose Childs, Lindsey M. Gonzalez-Velez, Miguel Lewis, James S., II TI Methicillin-resistant Staphylococcus aureus bacteraemia and endocarditis treated with ceftaroline salvage therapy SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE vancomycin-intermediate Staphylococcus aureus; VISA; pharmacodynamics; pharmacokinetics ID CEPHALOSPORIN; PATHOGENS AB One of the newest methicillin-resistant Staphylococcus aureus (MRSA) antibiotics to receive FDA approval is ceftaroline fosamil, a member of a new subclass of cephalosporins with unique activity against MRSA. However, ceftaroline is currently only FDA approved for complicated skin/soft tissue infections and community-acquired pneumonia; there are currently no clinical data regarding its use in MRSA bacteraemia and endocarditis. We report a series of six patients in which ceftaroline was utilized as salvage monotherapy in persistent MRSA bacteraemia or endocarditis. Using pharmacy records, 11 ceftaroline-treated patients were identified between January 2011 and November 2011 at University Health System and the South Texas Veterans Health Care System in San Antonio, TX, USA. All cases were reviewed and six patients received ceftaroline therapy for MRSA bacteraemia or endocarditis due to persistent or recurrent bacteraemia while on standard antibiotics (vancomycin or daptomycin). All six patients experienced rapid clearance of their bacteraemia after starting ceftaroline. In the case of endocarditis for which the patient subsequently developed heart failure and required valve replacement, there was no evidence of growth from cultures taken from the excised valve, suggesting sterilization within 13 days of starting ceftaroline. Ceftaroline exhibits potent anti-MRSA activity in both in vitro and animal studies, including rabbit endocarditis models; however, the lack of clinical data has limited its use in bacteraemia and endovascular infections in humans. We hope that this series serves as an initial stepping stone for further evaluation of this compound for more invasive infections due to MRSA. C1 [Lewis, James S., II] Univ Hlth Syst, Dept Pharm, San Antonio, TX 78229 USA. [Ho, Tony T.; Cadena, Jose; Gonzalez-Velez, Miguel; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA. [Cadena, Jose; Childs, Lindsey M.] Audie L Murphy Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Childs, Lindsey M.; Lewis, James S., II] Univ Texas Austin, Coll Pharm, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. RP Lewis, JS (reprint author), Univ Hlth Syst, Dept Pharm, 4502 Med Dr,MS 102, San Antonio, TX 78229 USA. EM james.lewis@uhs-sa.com NR 8 TC 53 Z9 53 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAY PY 2012 VL 67 IS 5 BP 1267 EP 1270 DI 10.1093/jac/dks006 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 921PJ UT WOS:000302489200035 PM 22311935 ER PT J AU Fischer, BL Gunter-Hunt, G Steinhafel, CH Howell, T AF Fischer, Barbara L. Gunter-Hunt, Gail Steinhafel, Courtney Holm Howell, Timothy TI The Identification and Assessment of Late-Life ADHD in Memory Clinics SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE adult ADHD; geriatric; cognition ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; ADULTS AB Objective: Little data exist about ADHD in late life. While evaluating patients' memory problems, the memory clinic staff has periodically identified ADHD in previously undiagnosed older adults. The authors conducted a survey to assess the extent to which other memory clinics view ADHD as a relevant clinical issue. Method: The authors developed and sent a questionnaire to memory clinics in the United States to determine the extent to which they identified patients with ADHD and the extent to which they took it into consideration. Results: Approximately one half of the memory clinics that responded reported seeing ADHD patients, either identifying previously diagnosed cases and/or newly diagnosing ADHD themselves. One fifth of clinics reported screening regularly for ADHD, and few clinics described accessing collateral informants to establish the diagnosis. Conclusion: This article suggests that U.S. memory clinics may not adequately identify and address ADHD in the context of late-life cognitive disorders. (J. of Att. Dis. 2012; 16(4) 333-338) C1 [Fischer, Barbara L.; Gunter-Hunt, Gail; Steinhafel, Courtney Holm; Howell, Timothy] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Howell, Timothy] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. RP Fischer, BL (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM barbara.fischer@va.gov FU William S. Middleton Memorial Veterans Hospital; Geriatric Research, Education, and Clinical Center (GRECC) FX The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article: William S. Middleton Memorial Veterans Hospital, Geriatric Research, Education, and Clinical Center (GRECC). This is GRECC manuscript No. 2008-02. NR 24 TC 2 Z9 2 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 J9 J ATTEN DISORD JI J. Atten. Disord. PD MAY PY 2012 VL 16 IS 4 BP 333 EP 338 DI 10.1177/1087054711398886 PG 6 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA 922UQ UT WOS:000302574300008 PM 22173147 ER PT J AU Garcia-Godoy, F Frankenberger, R Lohbauer, U Feilzer, AJ Kramer, N AF Garcia-Godoy, Franklin Frankenberger, Roland Lohbauer, Ulrich Feilzer, Albert J. Kraemer, Norbert TI Fatigue behavior of dental resin composites: Flexural fatigue in vitro versus 6 years in vivo SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE resin composites; flexural fatigue; clinical study; fracture; marginal fractureIntroduction ID FINE HYBRID COMPOSITE; POSTERIOR RESTORATIONS; CLINICAL-PERFORMANCE; WEAR AB Objectives: To evaluate fatigue behavior of direct resin composite restorations (Tetric Ceram vs. Grandio) in vitro and in vivo over an observation period of 6 years. Methods: For the in vitro part, Young's moduli (YM) were calculated and both initial (FS: flexural strength) and fatigue flexural strength (FFL: flexural fatigue limit) were evaluated in a four-point bending setup (n 15) in distilled water at 37 degrees C. For the in vivo part, 30 patients received 68 direct resin composite restorations of the same materials (Grandio bonded with Solobond M; Tetric Ceram bonded with Syntac). Patients revealed a minimum of two different class II restorations in different quadrants. Epoxy replicas of restored teeth were analyzed under a scanning electron microscope (SEM) at 30x magnification for fatigue characteristics, and 11 selected restorations per group were assessed for marginal fatigue characteristics at 200x. Results: In vitro, YM was 15.7 GPa (Grandio) and 8.7 GPa (Tetric Ceram; p < 0.05), FS was 115.0 MPa (Grandio) versus 101.5 MPa (Tetric Ceram; p > 0.05), and FFL was 63.0 MPa (Grandio) versus 44.3 MPa (Tetric Ceram; p < 0.05). In vivo, no significant difference in fatigue behavior (cracks, chippings) was evaluated for the different materials under investigation. However, marginal breakdown was more pronounced under the SEM for Tetric Ceram (7.9% vs. 4.8% for Grandio; p < 0.05), but without being clinically relevant. SEM analysis exhibited distinct wear patterns after 6 years with no significant differences among materials as well. Significances: Despite higher in vitro values for YM, FS, and FFL for Grandio, clinical outcome for both resin composite materials over 6 years of clinical service was similar. Higher FFLs in vitro seem to be related to less marginal composite fractures in vivo but without any influence on clinical outcome until the 6 years recall. (C) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 903-910, 2012. C1 [Frankenberger, Roland] Univ Med Ctr Giessen & Marburg, Dept Operat Dent & Endodont, Med Ctr Dent, D-35039 Marburg, Germany. [Garcia-Godoy, Franklin] Univ Tennessee, Coll Dent, Memphis, TN 38163 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Cambridge, MA USA. [Lohbauer, Ulrich] Univ Erlangen Nurnberg, Dent Clin Operat Dent & Periodontol 1, Univ Med Ctr, D-91054 Erlangen, Germany. [Feilzer, Albert J.] Univ Amsterdam, Acad Ctr Dent Amsterdam ACTA, Dept Dent Mat Sci, NL-1066 EA Amsterdam, Netherlands. [Kraemer, Norbert] Univ Med Ctr Giessen & Marburg, Dept Pediat Dent, Med Ctr Dent, D-35392 Giessen, Germany. RP Frankenberger, R (reprint author), Univ Med Ctr Giessen & Marburg, Dept Operat Dent & Endodont, Med Ctr Dent, Campus Marburg,Georg Voigt Str 3, D-35039 Marburg, Germany. EM frankbg@med.uni-marburg.de NR 33 TC 6 Z9 6 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD MAY PY 2012 VL 100B IS 4 BP 903 EP 910 DI 10.1002/jbm.b.32651 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 920KH UT WOS:000302402700003 PM 22323387 ER PT J AU Brown-Bowers, A Fredman, SJ Wanklyn, SG Monson, CM AF Brown-Bowers, Amy Fredman, Steffany J. Wanklyn, Sonya G. Monson, Candice M. TI Cognitive-Behavioral Conjoint Therapy for Posttraumatic Stress Disorder: Application to a Couple's Shared Traumatic Experience SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE posttraumatic stress disorder; PTSD; couple therapy; cognitive-behavioral conjoint therapy; psychotherapy AB Cognitive-behavioral conjoint therapy for posttraumatic stress disorder (CBCT for PTSD) is designed to improve PTSD symptoms and enhance intimate relationship adjustment. Phase 1 includes psychoeducation about the reciprocal influences of PTSD symptoms and relationship functioning, exercises to promote positive affect and behaviors, and conflict management skills. In Phase 2, behavioral methods are used to address avoidance and emotional numbing and to increase relationship satisfaction. Couples engage in activities to promote approaching, rather than avoiding, feared situations. Phase 3 focuses on specific trauma appraisals and here-and-now cognitions that maintain PTSD and relationship problems. This article provides an overview of the treatment, a review of the outcome research, and a case illustration of a couple with a shared trauma (a stillborn child). C1 [Monson, Candice M.] Ryerson Univ, Dept Psychol, Toronto, ON M5B 2K3, Canada. [Fredman, Steffany J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fredman, Steffany J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Monson, CM (reprint author), Ryerson Univ, Dept Psychol, 350 Victoria St, Toronto, ON M5B 2K3, Canada. EM can-dice.monson@psych.ryerson.ca FU NIMH NIH HHS [R34 MH076813] NR 8 TC 3 Z9 3 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAY PY 2012 VL 68 IS 5 BP 536 EP 547 DI 10.1002/jclp.21850 PG 12 WC Psychology, Clinical SC Psychology GA 925XX UT WOS:000302796800006 PM 22504612 ER PT J AU Yu, HY Hevelone, ND Lipsitz, SR Kowalczyk, KJ Nguyen, PL Hu, JC AF Yu, Hua-yin Hevelone, Nathanael D. Lipsitz, Stuart R. Kowalczyk, Keith J. Nguyen, Paul L. Hu, Jim C. TI Hospital Volume, Utilization, Costs and Outcomes of Robot-Assisted Laparoscopic Radical Prostatectomy SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatectomy; robotics; hospitals; demography ID PATIENT OUTCOMES; CANCER; SURGERY AB Purpose: Although robot-assisted laparoscopic radical prostatectomy has been aggressively marketed and rapidly adopted, there is a paucity of population based utilization, outcome and cost data. High vs low volume hospitals have better outcomes for open and minimally invasive radical prostatectomy (robotic or laparoscopic) but to our knowledge volume outcomes effects for robot-assisted laparoscopic radical prostatectomy alone have not been studied. Materials and Methods: We characterized robot-assisted laparoscopic radical prostatectomy outcome by hospital volume using the Nationwide Inpatient Sample during the last quarter of 2008. Propensity scoring methods were used to assess outcomes and costs. Results: At high volume hospitals robot-assisted laparoscopic radical prostatectomy was more likely to be done on men who were white with an income in the highest quartile and age less than 50 years than at low volume hospitals (each p <0.01). Hospitals at above the 50th volume percentile were less likely to show miscellaneous medical and overall complications (p = 0.01). Low vs high volume hospitals had longer mean length of stay (1.9 vs 1.6 days) and incurred higher median costs ($12,754 vs $8,623, each p <0.01). Conclusions: Demographic differences exist in robot-assisted laparoscopic radical prostatectomy patient populations between high and low volume hospitals. Higher volume hospitals showed fewer complications and lower costs than low volume hospitals on a national basis. These findings support referral to high volume centers for robot-assisted laparoscopic radical prostatectomy to decrease complications and costs. C1 [Yu, Hua-yin; Kowalczyk, Keith J.] Div Urol, Boston, MA USA. [Hevelone, Nathanael D.; Lipsitz, Stuart R.] Ctr Surg & Publ Hlth, Boston, MA USA. [Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Inst Urol Oncol, Los Angeles, CA 90024 USA. RP Hu, JC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Inst Urol Oncol, 924 Westwood Blvd,Suite 1000, Los Angeles, CA 90024 USA. EM jimhumd@gmail.com OI Hevelone, Nathanael/0000-0003-4740-2085 FU Department of Defense [W81XWH-08-1-0283]; American Urological Association Foundation FX Supported by Department of Defense Prostate Cancer Physician Training Award W81XWH-08-1-0283 (JCH) and an American Urological Association Foundation Research Scholars Award (HY). NR 27 TC 31 Z9 31 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 MAY PY 2012 VL 187 IS 5 BP 1632 EP 1637 DI 10.1016/j.juro.2011.12.071 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 925YD UT WOS:000302797500040 PM 22425094 ER PT J AU Conlin, MJ AF Conlin, Michael J. TI EDITORIAL COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Conlin, MJ (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. OI Conlin, Michael/0000-0002-3128-3731 NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2012 VL 187 IS 5 BP 1650 EP 1650 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 925YD UT WOS:000302797500052 PM 22425107 ER PT J AU Setsompop, K Gagoski, BA Polimeni, JR Witzel, T Wedeen, VJ Wald, LL AF Setsompop, Kawin Gagoski, Borjan A. Polimeni, Jonathan R. Witzel, Thomas Wedeen, Van J. Wald, Lawrence L. TI Blipped-controlled aliasing in parallel imaging for simultaneous multislice echo planar imaging with reduced g-factor penalty SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE parallel imaging; simultaneous multislice; CAIPIRINHA; wideband ID FUNCTIONAL MRI; BRAIN; EPI; RECONSTRUCTIONS; ACQUISITION; ARRAYS; GRAPPA; SIGNAL; FMRI; EVI AB Simultaneous multislice Echo Planar Imaging (EPI) acquisition using parallel imaging can decrease the acquisition time for diffusion imaging and allow full-brain, high-resolution functional MRI (fMRI) acquisitions at a reduced repetition time (TR). However, the unaliasing of simultaneously acquired, closely spaced slices can be difficult, leading to a high g-factor penalty. We introduce a method to create interslice image shifts in the phase encoding direction to increase the distance between aliasing pixels. The shift between the slices is induced using sign- and amplitude-modulated slice-select gradient blips simultaneous with the EPI phase encoding blips. This achieves the desired shifts but avoids an undesired tilted voxel blurring artifact associated with previous methods. We validate the method in 3X slice-accelerated spin-echo and gradient-echo EPI at 3 T and 7 T using 32-channel radio frequency (RF) coil brain arrays. The Monte-Carlo simulated average g-factor penalty of the 3-fold slice-accelerated acquisition with interslice shifts is <1% at 3 T (compared with 32% without slice shift). Combining 3X slice acceleration with 2X inplane acceleration, the g-factor penalty becomes 19% at 3 T and 10% at 7 T (compared with 41% and 23% without slice shift). We demonstrate the potential of the method for accelerating diffusion imaging by comparing the fiber orientation uncertainty, where the 3-fold faster acquisition showed no noticeable degradation. Magn Reson Med, 2012. (c) 2011 Wiley Periodicals, Inc. C1 [Setsompop, Kawin; Polimeni, Jonathan R.; Witzel, Thomas; Wedeen, Van J.; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Setsompop, Kawin; Polimeni, Jonathan R.; Wedeen, Van J.; Wald, Lawrence L.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Gagoski, Borjan A.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Witzel, Thomas; Wedeen, Van J.; Wald, Lawrence L.] MIT, Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Setsompop, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos PhD Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM kawin@nmr.mgh.harvard.edu RI Polimeni, Jonathan/P-1395-2014; Witzel, Thomas/P-1402-2014; Setsompop, Kawin/P-1464-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; Setsompop, Kawin/0000-0003-0455-7634; FU National Institutes of Health Institutes and Centers [1U01MH093765, K99EB012107, R01EB006847, R01EB007942] FX Grant sponsor: 16 National Institutes of Health Institutes and Centers that support the NIH Blueprint for Neuroscience (Human Connectome Project, 1U01MH093765); Grant numbers: K99EB012107, R01EB006847, R01EB007942 (NIH NIBIB grants), P41RR14075 (NCRR grant). NR 31 TC 200 Z9 201 U1 2 U2 27 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAY PY 2012 VL 67 IS 5 BP 1210 EP 1224 DI 10.1002/mrm.23097 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 923KY UT WOS:000302619400003 PM 21858868 ER PT J AU Hautvast, GLTF Salton, CJ Chuang, ML Breeuwer, M O'Donnell, CJ Manning, WJ AF Hautvast, Gilion L. T. F. Salton, Carol J. Chuang, Michael L. Breeuwer, Marcel O'Donnell, Christopher J. Manning, Warren J. TI Accurate computer-aided quantification of left ventricular parameters: Experience in 1555 cardiac magnetic resonance studies from the Framingham Heart Study SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE segmentation; postprocessing; technique development; technical research ID MR-IMAGES; SEGMENTATION; APPEARANCE; PROPAGATION AB Quantitative analysis of short-axis functional cardiac magnetic resonance images can be performed using automatic contour detection methods. The resulting myocardial contours must be reviewed and possibly corrected, which can be time-consuming, particularly when performed across all cardiac phases. We quantified the impact of manual contour corrections on both analysis time and quantitative measurements obtained from left ventricular short-axis cine images acquired from 1555 participants of the Framingham Heart Study Offspring cohort using computer-aided contour detection methods. The total analysis time for a single case was 7.6 +/- 1.7 min for an average of 221 +/- 36 myocardial contours per participant. This included 4.8 +/- 1.6 min for manual contour correction of 2% of all automatically detected endocardial contours and 8% of all automatically detected epicardial contours. However, the impact of these corrections on global left ventricular parameters was limited, introducing differences of 0.4 +/- 4.1 mL for end-diastolic volume, -0.3 +/- 2.9 mL for end-systolic volume, 0.7 +/- 3.1 mL for stroke volume, and 0.3 +/- 1.8% for ejection fraction. We conclude that left ventricular functional parameters can be obtained under 5 min from short-axis functional cardiac magnetic resonance images using automatic contour detection methods. Manual correction more than doubles analysis time, with minimal impact on left ventricular volumes and ejection fraction. Magn Reson Med, 2012. (c) 2011 Wiley Periodicals, Inc. C1 [Hautvast, Gilion L. T. F.; Breeuwer, Marcel] Philips Healthcare, Imaging Syst, MR, NL-5680 DA Best, Netherlands. [Salton, Carol J.; Chuang, Michael L.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Salton, Carol J.; Chuang, Michael L.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Chuang, Michael L.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Breeuwer, Marcel] Eindhoven Univ Technol, NL-5600 MB Eindhoven, Netherlands. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Hautvast, GLTF (reprint author), Philips Healthcare, Imaging Syst, MR, Veenpluis 4-6, NL-5680 DA Best, Netherlands. EM gilion.hautvast@philips.com; marcel.breeuwer@philips.com FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; National Institutes of Health [N01-HC-25195, RO1 HL70279]; Philips Healthcare FX Grant sponsor: National Heart, Lung and Blood Institute's Framingham Heart Study; Grant number: N01-HC-25195; Grant sponsor: National Institutes of Health; Grant number: N01-HC-25195 is a subcontract of RO1 HL70279; Grant sponsor: unrestricted grant from Philips Healthcare. NR 25 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAY PY 2012 VL 67 IS 5 BP 1478 EP 1486 DI 10.1002/mrm.23127 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 923KY UT WOS:000302619400029 PM 22021128 ER PT J AU De Jager, PL Shulman, JM Chibnik, LB Keenan, BT Raj, T Wilson, RS Yu, L Leurgans, SE Tran, D Aubin, C Anderson, CD Biffi, A Corneveaux, JJ Huentelman, MJ Rosand, J Daly, MJ Myers, AJ Reiman, EM Bennett, DA Evans, DA AF De Jager, Philip L. Shulman, Joshua M. Chibnik, Lori B. Keenan, Brendan T. Raj, Towfique Wilson, Robert S. Yu, Lei Leurgans, Sue E. Tran, Dong Aubin, Cristin Anderson, Christopher D. Biffi, Alessandro Corneveaux, Jason J. Huentelman, Matthew J. Rosand, Jonathan Daly, Mark J. Myers, Amanda J. Reiman, Eric M. Bennett, David A. Evans, Denis A. CA Alzheimer's Dis Neuroimaging Initi TI A genome-wide scan for common variants affecting the rate of age-related cognitive decline SO NEUROBIOLOGY OF AGING LA English DT Article DE Cognitive decline; Genome-wide association study; Alzheimer's disease; Genetic risk score ID APOLIPOPROTEIN-E EPSILON-4; ISCHEMIC CEREBROVASCULAR-DISEASE; ALZHEIMERS-DISEASE; OLDER PERSONS; NEURODEGENERATIVE DISEASE; IDENTIFIES VARIANTS; CLINICAL-DIAGNOSIS; GENE-EXPRESSION; MESSENGER-RNA; RISK-FACTORS AB Age-related cognitive decline is likely promoted by accumulated brain injury due to chronic conditions of aging, including neurodegenerative and vascular disease. Because common neuronal mechanisms may mediate the adaptation to diverse cerebral insults, we hypothesized that susceptibility for age-related cognitive decline may be due in part to a shared genetic network. We have therefore performed a genome-wide association study using a quantitative measure of global cognitive decline slope, based on repeated measures of 17 cognitive tests in 749 subjects from the Religious Orders Study. Top results were evaluated in 3 independent replication cohorts, consisting of 2279 additional subjects with repeated cognitive testing. As expected, we find that the Alzheimer's disease (AD) susceptibility locus, APOE, is strongly associated with rate of cognitive decline (P-DISC = 5.6 x 10(-9); P-JOINT = 3.7 x 10(-27)). We additionally discover a variant, rs10808746, which shows consistent effects in the replication cohorts and modestly improved evidence of association in the joint analysis (P-DISC = 6.7 x 10(-5); P-REP = 9.4 x 10(-3); P-JOINT = 2.3 x 10(-5)). This variant influences the expression of 2 adjacent genes, PDE7A and MTFR1, which are potential regulators of inflammation and oxidative injury, respectively. Using aggregate measures of genetic risk, we find that known susceptibility loci for cardiovascular disease, type 2 diabetes, and inflammatory diseases are not significantly associated with cognitive decline in our cohort. Our results suggest that intermediate phenotypes, when coupled with larger sample sizes, may be a useful tool to dissect susceptibility loci for age-related cognitive decline and uncover shared molecular pathways with a role in neuronal injury. (C) 2012 Elsevier Inc. All rights reserved. C1 [De Jager, Philip L.; Shulman, Joshua M.; Chibnik, Lori B.; Keenan, Brendan T.; Raj, Towfique; Tran, Dong; Aubin, Cristin] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Inst Neurosci, Boston, MA 02115 USA. [De Jager, Philip L.; Shulman, Joshua M.; Chibnik, Lori B.; Keenan, Brendan T.; Raj, Towfique; Tran, Dong; Aubin, Cristin] Brigham & Womens Hosp, Dept Psychiat, Program Translat NeuroPsychiat Genom, Inst Neurosci, Boston, MA 02115 USA. [De Jager, Philip L.; Shulman, Joshua M.; Chibnik, Lori B.; Raj, Towfique; Tran, Dong; Aubin, Cristin; Rosand, Jonathan; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. [De Jager, Philip L.; Shulman, Joshua M.; Chibnik, Lori B.; Keenan, Brendan T.; Tran, Dong; Aubin, Cristin; Anderson, Christopher D.; Biffi, Alessandro; Rosand, Jonathan; Daly, Mark J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Wilson, Robert S.; Yu, Lei; Leurgans, Sue E.; Bennett, David A.; Evans, Denis A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Anderson, Christopher D.; Biffi, Alessandro; Rosand, Jonathan; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Anderson, Christopher D.; Biffi, Alessandro; Rosand, Jonathan; Daly, Mark J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Corneveaux, Jason J.; Huentelman, Matthew J.; Reiman, Eric M.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA. [Corneveaux, Jason J.; Huentelman, Matthew J.; Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ USA. [Myers, Amanda J.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Myers, Amanda J.] Johnnie B Byrd Sr Alzheimers Ctr & Res Inst, Tampa, FL USA. [Reiman, Eric M.] Univ Arizona, Banner Alzheimers Inst, Phoenix, AZ USA. [Reiman, Eric M.] Univ Arizona, Dept Psychiat, Phoenix, AZ USA. [Reiman, Eric M.] Univ Arizona, Dept Psychiat, Tucson, AZ USA. [Evans, Denis A.] Rush Univ, Med Ctr, Rush Inst Hlth Aging, Chicago, IL 60612 USA. RP De Jager, PL (reprint author), Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Inst Neurosci, 77 Ave Louis Pasteur,NRB 168C, Boston, MA 02115 USA. EM pdejager@rics.bwh.harvard.edu; Denis_Evans@rush.edu RI Myers, Amanda/B-1796-2010; OI Myers, Amanda/0000-0002-3100-9396; Anderson, Christopher/0000-0002-0053-2002 FU National Institutes of Health [R01 AG030146, P30 AG10161, R01 AG17917, R01 AG15819, K08 AG034290, R01 AG11101, 1P30 AG010129, K01 AG030514]; Illinois Department of Public Health; Beth Israel Deaconess Medical Center; Harvard/MIT Health Sciences and Technology; Pfizer Inc.; Merck Co.; NIA [R01 AG034504, K01AG024079, P50 AG23173]; Johnnie B Byrd Institute; Kronos Life Sciences Laboratories, the National Institute on Aging (Arizona Alzheimer's Disease Center) [P30 AG19610, R01 AG023193]; Kronos Life Sciences Laboratories, the National Institute on Aging (Mayo Clinic Alzheimer's Disease Center) [P50 AG16574]; National Alzheimer's Coordinating Center [U01 AG016976]; state of Arizona; NIH Neuroscience Blueprint [U24NS051872]; ENDGAME Consortium [U01HL084744]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute of Biomedical Imaging and Bioengineering; Dana Foundation FX The authors thank Sara Pulit for help with assembling a comprehensive list of SNPs associated with inflammatory diseases. The authors are also grateful to the participants in the Religious Orders Study, the Chicago Health and Aging Project, the Memory and Aging Project, and the Alzheimer's Disease Neuroimaging Initiative. This work is supported by the National Institutes of Health [R01 AG030146, P30 AG10161, R01 AG17917, R01 AG15819, K08 AG034290, P30 AG10161 and R01 AG11101], and the Illinois Department of Public Health. J.M.S. is additionally supported by the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center and Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Co. A.J.M. is supported by NIA grant R01 AG034504 and the Johnnie B Byrd Institute. M.J.H., J.C., and E. M. R. are supported by grants from Kronos Life Sciences Laboratories, the National Institute on Aging (Arizona Alzheimer's Disease Center P30 AG19610, R01 AG023193, Mayo Clinic Alzheimer's Disease Center P50 AG16574 and Intramural Research Program), the National Alzheimer's Coordinating Center (U01 AG016976), and the state of Arizona. Additional funding was obtained from the NIH Neuroscience Blueprint (U24NS051872), the ENDGAME Consortium (U01HL084744), a National Institute on Aging grant to Carl Cotman (University of California, Irvine, P50 AG23173), National Institute on Aging (K01AG024079) and the state of Arizona. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants; 1P30 AG010129, K01 AG030514, and the Dana Foundation. NR 81 TC 9 Z9 9 U1 0 U2 4 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 MAY PY 2012 VL 33 IS 5 AR 1017.e1 DI 10.1016/j.neurobiolaging.2011.09.033 PG 15 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 921OF UT WOS:000302486200052 PM 22054870 ER PT J AU Wang, L Murphy, NP Stengel, A Goebel-Stengel, M St Pierre, DH Maidment, NT Tache, Y AF Wang, L. Murphy, N. P. Stengel, A. Goebel-Stengel, M. St Pierre, D. H. Maidment, N. T. Tache, Y. TI Ghrelin prevents levodopa-induced inhibition of gastric emptying and increases circulating levodopa in fasted rats SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE dopamine; gastric emptying; ghrelin; levodopa; rats ID PARKINSONS-DISEASE; FOS EXPRESSION; IN-VITRO; RESPONSE FLUCTUATIONS; GASTROINTESTINAL MOTILITY; SOLITARY TRACT; FOOD-INTAKE; GUINEA-PIG; C-FOS; SECRETION AB Background Levodopa (l-dopa) is the most commonly used treatment for alleviating symptoms of Parkinsons disease. However, l-dopa delays gastric emptying, which dampens its absorption. We investigated whether ghrelin prevents l-dopa action on gastric emptying and enhances circulating l-dopa in rats. Methods Gastric emptying of non-nutrient methylcellulose/phenol red viscous solution was determined in fasted rats treated with orogastric or intraperitoneal (i.p.) L-dopa, or intravenous (i.v.) ghrelin 10 min before orogastric L-dopa. Plasma L-dopa and dopamine levels were determined by high pressure liquid chromatography. Plasma acyl ghrelin levels were assessed by radioimmunoassay. Fos expression in the brain was immunostained after i. v. ghrelin (30 lg kg(-1)) 10 min before i.p. L-dopa. Key Results Levodopa (5 and 15 mg kg(-1)) decreased significantly gastric emptying by 32% and 62%, respectively, when administered orally, and by 91% and 83% when injected i.p. Ghrelin (30 or 100 lg kg(-1), i. v.) completely prevented L-dopa's (15 mg kg(-1), orogastrically) inhibitory action on gastric emptying and enhanced plasma L-dopa and dopamine levels compared with vehicle 15 min after orogastric L-dopa. Levodopa (5 mg kg(-1)) did not modify plasma acyl ghrelin levels at 30 min, 1, and 2 h after i. v. injection. Levodopa (15 mg kg(-1), i.p.) induced Fos in brain autonomic centers, which was not modified by i. v. ghrelin. Conclusions& Inferences Ghrelin counteracts L-dopa-induced delayed gastric emptying but not Fos induction in the brain and enhances circulating L-dopa levels. Potential therapeutic benefits of ghrelin agonists in Parkinson's disease patients treated with L-dopa remain to be investigated. C1 [Wang, L.; Stengel, A.; Goebel-Stengel, M.; Tache, Y.] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Ctr, Los Angeles, CA 90024 USA. [Wang, L.; Stengel, A.; Goebel-Stengel, M.; Tache, Y.] Univ Calif Los Angeles, Div Digest Dis, Ctr Neurobiol Stress, Los Angeles, CA USA. [Wang, L.; Stengel, A.; Goebel-Stengel, M.; Tache, Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Murphy, N. P.; Maidment, N. T.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Dept Psychol, Los Angeles, CA 90095 USA. [St Pierre, D. H.] Univ Montreal, Montreal, PQ, Canada. RP Wang, L (reprint author), Bldg 115,Rm 117B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM lixinw@ucla.edu FU Michael J. Fox Foundation for Parkinson's Research, NIH Center [DK-41301]; Veterans Administration FX This work was supported by the Michael J. Fox Foundation for Parkinson's Research, NIH Center Grant DK-41301 (Animal Core) and Veterans Administration Research Career Scientist Award (Y.T.). We are grateful to Mrs. Honghui Liang and Ms. Rachel Kelly for excellent technical support and we thank Ms. Eugenia Hu for reviewing the manuscript. NR 72 TC 14 Z9 14 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAY PY 2012 VL 24 IS 5 BP e235 EP e245 DI 10.1111/j.1365-2982.2012.01904.x PG 11 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 923IH UT WOS:000302612500002 PM 22443313 ER PT J AU Rhein, L Simoneau, T Davis, J Correia, C Ferrari, D Monuteaux, M Gregory, M AF Rhein, Lawrence Simoneau, Tregony Davis, Jaclyn Correia, Catherine Ferrari, Dan Monuteaux, Michael Gregory, MaryLucia TI Reference values of nocturnal oxygenation for use in outpatient oxygen weaning protocols in premature infants SO PEDIATRIC PULMONOLOGY LA English DT Article DE hypoxemia; pulse oximetry; reference values; weaning; prematurity ID BIRTH-WEIGHT OUTCOMES; DEVELOPMENT NEONATAL NETWORK; CHRONIC LUNG-DISEASE; PRETERM INFANTS; SLEEP-APNEA; SATURATION; MANAGEMENT; AUSTRALIA; HYPOXEMIA; DISCHARGE AB Objective To define reference ranges for oxygen saturation (SpO2) values in healthy full-term infants in the first days of life and in preterm infants off supplemental oxygen as they approach neonatal intensive care unit (NICU) discharge. Methods: From April 2009 to March 2010, we enrolled convenience samples of full-term infants from the newborn nursery and former preterm infants who did not require supplemental oxygen at the time of discharge from the NICU. Overnight SpO(2) and signal quality recordings were obtained and analyzed for duration of artifact-free recording time (AFRT), time (s) with SpO(2) less than several different target saturations (90-95%), and number of falls in SpO(2) by >= 4% and >= 10%. Results: We studied 102 full-term infants and 52 preterm infants. Preterm and full-term infants spent similar amounts of time less than 90%, 91%, 92%, 93%, 94%, and 95% although preterm infants had more falls in SpO(2) by >= 4% per hour of AFRT. Over 67% of term and preterm infants spent less than 6% of their time below 93%. Conclusion: These data represent reference SpO(2) ranges for both preterm infants not requiring supplemental oxygen at NICU discharge and full-term infants in the first days of life. As we currently lack guidelines dictating the optimal target oxygen saturations for infants and the acceptable maximal time that they can safely spend below set target saturations, our data may serve as a guide to interpreting SpO(2) recordings of premature outpatient infants who are weaning from supplemental oxygen. Pediatr Pulmonol. 2012; 47: 453-459. (C) 2011 Wiley Periodicals, Inc. C1 [Rhein, Lawrence; Simoneau, Tregony; Correia, Catherine; Ferrari, Dan] Childrens Hosp, Div Resp Dis, Boston, MA 02115 USA. [Rhein, Lawrence] Childrens Hosp, Div Neonatol, Boston, MA 02115 USA. [Rhein, Lawrence; Simoneau, Tregony; Correia, Catherine; Ferrari, Dan; Monuteaux, Michael; Gregory, MaryLucia] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Davis, Jaclyn] Massachusetts Gen Hosp, Div Genet, Boston, MA 02114 USA. [Monuteaux, Michael] Childrens Hosp, Div Biostat, Boston, MA 02115 USA. [Gregory, MaryLucia] Beth Israel Deaconess Med Ctr, Dept Neonatol, Boston, MA 02215 USA. RP Rhein, L (reprint author), Boston Childrens Hosp, Dept Resp Dis & Newborn Med, 300 Longwood Ave, Boston, MA 02467 USA. EM lawrence.rhein@childrens.harvard.edu FU NICUs at Beth Israel Deaconess Medical Center; Brigham; Women's Hospital FX We acknowledge the parents and infants who participated in this study, and the support of staff in the nurseries and NICUs at Beth Israel Deaconess Medical Center and Brigham and Women's Hospital. We also thank Masimo for loaning the oximeters and providing oximetry probes required to complete this study. Masimo had no input into study design, and did not influence the reporting of any results. NR 28 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD MAY PY 2012 VL 47 IS 5 BP 453 EP 459 DI 10.1002/ppul.21562 PG 7 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 923ND UT WOS:000302625100006 PM 22102606 ER PT J AU Boyd, AS Rodrigues, NP Lui, KO Fu, XM Xu, Y AF Boyd, Ashleigh S. Rodrigues, Neil P. Lui, Kathy O. Fu, Xuemei Xu, Yang TI Concise Review: Immune Recognition of Induced Pluripotent Stem Cells SO STEM CELLS LA English DT Article DE Stem cells; Embryonic stem cells; Induced pluripotent stem cells; Cell replacement therapy; Immunogenicity; Transplantation; Tolerance; Rejection; Regenerative medicine ID REGULATORY T-CELLS; LONG-TERM ACCEPTANCE; HUMAN SOMATIC-CELLS; DIFFERENTIATED DERIVATIVES; COSTIMULATION BLOCKADE; CARDIAC ALLOGRAFTS; DENDRITIC CELLS; DEFINED FACTORS; BLOCKING CD40; CD28 PATHWAYS AB Autologous-induced pluripotent stem cells (iPSCs) may eventually be used in cell replacement therapies to treat a wide range of diseases and have been touted as a solution to the vexing problem of immune rejection in this context. Emerging evidence suggests, however, that ostensibly histocompatible iPSCs may be rejected following transplantation. Here, we review the mechanisms that contribute to immunogenicity in iPSCs and forward approaches to permit their acceptance in potential cell replacement therapies. STEM CELLS 2012;30:797803 C1 [Boyd, Ashleigh S.; Rodrigues, Neil P.] Boston Univ, NIH, Ctr Biomed Res Excellence COBRE Stem Cell Biol, Roger Williams Canc Med Ctr,Sch Med, Providence, RI 02908 USA. [Boyd, Ashleigh S.; Rodrigues, Neil P.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Boyd, Ashleigh S.; Rodrigues, Neil P.] Boston Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02118 USA. [Lui, Kathy O.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Boston, MA USA. [Fu, Xuemei; Xu, Yang] Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA. [Fu, Xuemei] Chengdu Womens & Childrens Cent Hosp, Chengdu, Sichuan, Peoples R China. RP Boyd, AS (reprint author), Boston Univ, NIH, COBRE, Roger Williams Canc Med Ctr,Sch Med,Prior Off 207, 825 Chalkstone Ave, Providence, RI 02908 USA. EM asboyd@bu.edu; yangxu@ucsd.edu RI Lui, Kathy O./E-4883-2015 OI Lui, Kathy O./0000-0002-1616-3643 FU NIH [P20RR018757]; Rhode Island Foundation; BD Biosciences; NSFC [30872346]; California Institute for Regenerative Medicine [TR1-01277]; NIH COBRE at Roger Williams Medical Center FX This work was supported by NIH Grant P20RR018757 (A.S.B. and N.P.R.), Rhode Island Foundation (A.S.B.), BD Biosciences (N.P.R.), a NSFC Grant 30872346 (X.F.), and California Institute for Regenerative Medicine Grant TR1-01277 (Y.X.). Additional support to A.S.B. and N.P.R. laboratories is provided by the administrative and flow cytometry cores within the NIH COBRE at Roger Williams Medical Center. NR 53 TC 26 Z9 27 U1 1 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAY PY 2012 VL 30 IS 5 BP 797 EP 803 DI 10.1002/stem.1066 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 923KD UT WOS:000302617300001 PM 22419544 ER PT J AU Gellhorn, AC Morgenroth, DC Goldstein, B AF Gellhorn, Alfred C. Morgenroth, David C. Goldstein, Barry TI A NOVEL SONOGRAPHIC METHOD OF MEASURING PATELLAR TENDON LENGTH SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE Tendon; Tendinopathy; Measurement; Ultrasound; Interrater reliability; Patellar; Patella alta; Infera; Baja ID FIELD-OF-VIEW; CRUCIATE LIGAMENT RECONSTRUCTION; ACHILLES-TENDON; IN-VIVO; ULTRASOUND; ULTRASONOGRAPHY; MUSCLE; ALTA; US AB Obtaining accurate and readily repeatable measurements is a prerequisite for using measures of soft tissue structures both clinically and in the research setting. Few studies have evaluated the interrater reliability of ultrasound measurements of tendons. The objective of this study was to determine the accuracy and reliability of a new method of sonographic measurement of patellar tendon length using direct dissection as the gold standard. Four cadaveric knees were sonographically evaluated by two independent investigators. Two custom designed straps with nylon strapping and stainless steel wire were used to firmly mark position on the leg and create an acoustic shadow on the ultrasound image. Anatomic landmarks were the distal patellar pole and the bony ridge on the anterior proximal tibia. After sonographic evaluation, the knee was dissected to expose the patellar tendon, which was measured using digital calipers. Intraclass correlation coefficients (ICC) were used to determine reliability of measurements between observers, where ICC > 0.75 was considered good and >0.9 was considered excellent. Validity was measured using a Bland-Altman plot, which measures bias between measurement methods as well as variability of scatter. Three sonographic measurements were made by each investigator on each tendon. The length of each of the four tendons based on the mean values of sonographic measurements was 53.8 mm, 53.4 mm, 49.4 mm and 46.8 mm. The length based on visual inspection of the dissected tissue was 54.6 mm, 52.8 mm, 49.8 mm and 46.9 mm. The calculated ICC between raters was 0.96. On the Bland-Altman plot, the bias, or mean difference between sonographic and visual measures, was 0.17 mm, with a standard deviation of 0.71. The 95% limit of agreement was 21.55 to 1.22 mm. Measurement of patellar tendon length with ultrasound using adjustable surface markers and calipers is highly accurate and has good interrater reliability. (E-mail: gellhorn@uw.edu) (C) 2012 World Federation for Ultrasound in Medicine & Biology. C1 [Gellhorn, Alfred C.; Morgenroth, David C.; Goldstein, Barry] Univ Washington, Dept Rehabil Med, Seattle, WA 98105 USA. [Morgenroth, David C.] VA Puget Sound Hlth Care Syst, Rehabil Res & Dev Ctr, Seattle, WA USA. RP Gellhorn, AC (reprint author), Univ Washington, Dept Rehabil Med, 4245 Roosevelt Way,NE,Box 354740, Seattle, WA 98105 USA. EM gellhorn@uw.edu OI Morgenroth, David/0000-0002-0226-7775 FU Walter and Anita Stolov Fund FX This work was supported by a grant from the Walter and Anita Stolov Fund. NR 28 TC 5 Z9 5 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD MAY PY 2012 VL 38 IS 5 BP 719 EP 726 DI 10.1016/j.ultrasmedbio.2012.01.020 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 922VZ UT WOS:000302577900001 PM 22425379 ER PT J AU Dershwitz, P Dostalova, Z Parker, K Stewart, D Miller, KW Forman, SA AF Dershwitz, P. Dostalova, Z. Parker, K. Stewart, D. Miller, K. W. Forman, S. A. TI ALPHA-E432: A NOVEL TORPEDO NICOTINIC ACETYLCHOLINE RECEPTOR AZI OCTANOL PHOTOLABEL SITE SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Dershwitz, P.; Dostalova, Z.; Stewart, D.; Miller, K. W.; Forman, S. A.] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Parker, K.] Virgin Instruments Corp, Sudbury, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-422 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600234 ER PT J AU Feng, H Jounaidi, Y Forman, SA AF Feng, H. Jounaidi, Y. Forman, S. A. TI MODULATION OF delta SUBUNIT-CONTAINING GABAA RECEPTORS BY ETOMIDATE DEPENDS ON SUBUNIT ARRANGEMENT SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Feng, H.; Jounaidi, Y.; Forman, S. A.] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-427 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600238 ER PT J AU Haburcak, M Stewart, D Jounaidi, Y Forman, SA AF Haburcak, M. Stewart, D. Jounaidi, Y. Forman, S. A. TI ANESTHETIC EFFECTS ON SYNAPTIC GABAA RECEPTORS CONTAINING beta 3 SUBUNITS ARE QUANTITATIVELY SIMILAR TO RECEPTORS CONTAINING beta 2 SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Haburcak, M.; Stewart, D.; Jounaidi, Y.; Forman, S. A.] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-421 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600233 ER PT J AU Ishizawa, Y Uchida, A Gale, JT Brown, EN Eskandar, EN AF Ishizawa, Y. Uchida, A. Gale, J. T. Brown, E. N. Eskandar, E. N. TI SELECTIVE INHIBITION OF PROPOFOL IN CORTICAL SINGLE NEURONS IN THE MACAQUE BRAIN SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Ishizawa, Y.; Uchida, A.; Brown, E. N.] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Gale, J. T.; Eskandar, E. N.] Massachusetts Gen Hosp, Neurosurg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-424 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600235 ER PT J AU Iwasaki, H Takahoko, K Otomo, S Sasakawa, T Kunisawa, T Iwasaki, H AF Iwasaki, H. Takahoko, K. Otomo, S. Sasakawa, T. Kunisawa, T. Iwasaki, H. TI PREDICTION OF ADDITIONAL SUGAMMADEX IN A SHORT RECOVERY PHASE IN PEDIATRIC PATIENTS SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Iwasaki, H.; Takahoko, K.; Otomo, S.; Kunisawa, T.; Iwasaki, H.] Asahikawa Med Univ, Dept Anesthesiol & Crit Care Med, Asahikawa, Hokkaido, Japan. [Sasakawa, T.] Harvard Med Sch, Massachusetts Gen Hosp, Shriners Hosp Children, Dept Anesthesiol,Shriners Burns Inst, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-452 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600255 ER PT J AU Johnson-Akeju, O Eggan, K AF Johnson-Akeju, O. Eggan, K. TI EMBRYONIC STEM CELL BASED INSIGHTS INTO ANESTHESIA INDUCED COGNITIVE DEFICIT: A ROLE FOR ALTERED NEUROGENESIS SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Johnson-Akeju, O.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Eggan, K.] Harvard Stem Cell Inst, Stem Cell & Regenerat Biol, Cambridge, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-405 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600225 ER PT J AU Kida, K Minamishima, S Ichinose, F AF Kida, K. Minamishima, S. Ichinose, F. TI SODIUM SULFIDE PREVENTS WATER DIFFUSION ABNORMALITY IN THE BRAIN AND IMPROVES LONG TERM OUTCOME AFTER CARDIAC ARREST IN MICE SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-164 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600066 ER PT J AU Lau, J Minehart, R Derevianko, A Mai, C AF Lau, J. Minehart, R. Derevianko, A. Mai, C. TI USING HIGH-FIDELITY SIMULATION AND SKILLS TRAINING IN-SITU TO PREPARE ANESTHESIOLOGY RESIDENTS FOR A PEDIATRIC ANESTHESIA ROTATION SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Lau, J.; Minehart, R.; Derevianko, A.; Mai, C.] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-231 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600121 ER PT J AU Liu, Y Pian-Smith, MM Leffert, LR Minehart, R Kacmarek, RM Jiang, Y AF Liu, Y. Pian-Smith, M. M. Leffert, L. R. Minehart, R. Kacmarek, R. M. Jiang, Y. TI HEMODYNAMIC PROFILE OF PATIENTS HAVING CESAREAN DELIVERY UNDER SPINAL ANESTHESIA OBTAINED BY CONTINUOUS MEASUREMENT OF CARDIAC OUTPUT AND STROKE VOLUME SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Liu, Y.; Pian-Smith, M. M.; Leffert, L. R.; Minehart, R.; Kacmarek, R. M.; Jiang, Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-334 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600186 ER PT J AU Mirzakhani, H Welch, CA George, E MacDonald, TO Nozari, A Eikermann, M AF Mirzakhani, H. Welch, C. A. George, E. MacDonald, T. O. Nozari, A. Eikermann, M. TI OPTIMAL CONTROL OF MUSCLE RELAXATION FOR ELECTROCONVULSIVE THERAPY: A COMPARISON OF SUCCINYLCHOLINE VERSUS ROCURONIUM-INDUCED NEUROMUSCULAR BLOCKADE SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Mirzakhani, H.; George, E.; MacDonald, T. O.; Nozari, A.; Eikermann, M.] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Welch, C. A.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Mirzakhani, H.; Welch, C. A.; George, E.; MacDonald, T. O.; Nozari, A.; Eikermann, M.] Harvard Med Sch, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-449 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600253 ER PT J AU Parker, MJ Lovich, MA Sims, NM Peterfreund, RA AF Parker, M. J. Lovich, M. A. Sims, N. M. Peterfreund, R. A. TI AN ALGORITHM FOR COMPUTER CONTROL OF DRUG DELIVERY BY CONTINUOUS INTRAVENOUS INFUSION: REDUCTION OF DELIVERY ONSET LAG TIME IN A LABORATORY MODEL SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Parker, M. J.] Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. [Lovich, M. A.] St Elizabeths Med Ctr, Dept Anesthesiol & Pain Med, Boston, MA USA. [Sims, N. M.; Peterfreund, R. A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-246 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600130 ER PT J AU Pierce, DW Pejo, E Haburcak, M Raines, DE Forman, SA AF Pierce, D. W. Pejo, E. Haburcak, M. Raines, D. E. Forman, S. A. TI CARBOETOMIDATE INHIBITS alpha 4 beta 2 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS AT CLINICALLY RELEVANT CONCENTRATIONS SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Pierce, D. W.; Pejo, E.; Haburcak, M.; Raines, D. E.; Forman, S. A.] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-418 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600231 ER PT J AU Savechenkov, PY Stewart, D Zhang, X Ge, R Bruzik, KS Miller, KW AF Savechenkov, P. Y. Stewart, D. Zhang, X. Ge, R. Bruzik, K. S. Miller, K. W. TI ALLYL TFD-MEPHOBARBITAL : POTENT ENANTIOSELECTIVE PHOTOREACTIVE BARBITURATE GENERAL ANESTHETICS THAT INTERACT WITH HUMAN GABA(A) RECEPTORS SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Stewart, D.; Zhang, X.; Ge, R.; Miller, K. W.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Savechenkov, P. Y.; Bruzik, K. S.] Univ Illinois, Coll Pharm, Chicago, IL USA. [Zhang, X.; Miller, K. W.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-438 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600248 ER PT J AU Takahoko, K Iwasaki, H Otomo, S Sasakawa, T Iwasaki, H AF Takahoko, K. Iwasaki, H. Otomo, S. Sasakawa, T. Iwasaki, H. TI USEFULNESS OF ESTIMATED PLASMA CONCENTRATION (CP) FOR DECIDING THE TIMING OF REPEATED BOLUS ROCURONIUM ADMINISTRATION UNDER DESFLURANE ANESTHESIA SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Takahoko, K.; Iwasaki, H.; Otomo, S.; Iwasaki, H.] Asahikawa Med Coll, Anesthesiol, Asahikawa, Hokkaido, Japan. [Sasakawa, T.] Harvard Med Sch, Massachusetts Gen Hosp, Shriners Hosp Children, Shriners Burns Inst,Anesthesiol, Cambridge, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-458 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600260 ER PT J AU Tokuda, K Marutani, E Kida, K Ichinose, F AF Tokuda, K. Marutani, E. Kida, K. Ichinose, F. TI INHALED HYDROGEN SULFIDE PREVENTS ENDOTOXIN-INDUCED SYSTEMIC INFLAMMATION AND IMPROVES SURVIVAL BY ALTERING SULFIDE METABOLISM IN MICE SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Tokuda, K.; Marutani, E.; Kida, K.; Ichinose, F.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-163 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600065 ER PT J AU Wanderer, JP Baker, KH Forman, SA AF Wanderer, J. P. Baker, K. H. Forman, S. A. TI PLATFORM FOR OPERATING ROOM TEACHING AND LEARNING (PORTAL): DEVELOPMENT OF A NEW EDUCATIONAL PARADIGM SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 18-21, 2012 CL Boston, MA C1 [Wanderer, J. P.; Baker, K. H.; Forman, S. A.] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2012 VL 114 SU 1 MA S-232 PG 1 WC Anesthesiology SC Anesthesiology GA V45WL UT WOS:000209846600122 ER PT J AU Lieberman, AP Puertollano, R Raben, N Slaugenhaupt, S Walkley, SU Ballabio, A AF Lieberman, Andrew P. Puertollano, Rosa Raben, Nina Slaugenhaupt, Susan Walkley, Steven U. Ballabio, Andrea TI Autophagy in lysosomal storage disorders SO AUTOPHAGY LA English DT Review DE autophagy; glycogenosis; Mucolipidosis Type IV; lysosomal storage disorders; mucopolysaccharidoses; lysosomes; sphingolipidoses ID MUCOLIPIDOSIS TYPE-IV; MULTIPLE SULFATASE DEFICIENCY; PICK-C DISEASE; PHOSPHOTRANSFERASE ALPHA/BETA-SUBUNITS; NEURONAL CEROID-LIPOFUSCINOSIS; ENZYME REPLACEMENT THERAPY; SINGLE MUSCLE-FIBERS; POMPE-DISEASE; MOUSE MODEL; GAUCHER-DISEASE AB Lysosomes are ubiquitous intracellular organelles that have an acidic internal pH, and play crucial roles in cellular clearance. Numerous functions depend on normal lysosomes, including the turnover of cellular constituents, cholesterol homeostasis, downregulation of surface receptors, inactivation of pathogenic organisms, repair of the plasma membrane and bone remodeling. Lysosomal storage disorders (LSDs) are characterized by progressive accumulation of undigested macromolecules within the cell due to lysosomal dysfunction. As a consequence, many tissues and organ systems are affected, including brain, viscera, bone and cartilage. The progressive nature of phenotype development is one of the hallmarks of LSDs. In recent years biochemical and cell biology studies of LSDs have revealed an ample spectrum of abnormalities in a variety of cellular functions. These include defects in signaling pathways, calcium homeostasis, lipid biosynthesis and degradation and intracellular trafficking. Lysosomes also play a fundamental role in the autophagic pathway by fusing with autophagosomes and digesting their content. Considering the highly integrated function of lysosomes and autophagosomes it was reasonable to expect that lysosomal storage in LSDs would have an impact upon autophagy. The goal of this review is to provide readers with an overview of recent findings that have been obtained through analysis of the autophagic pathway in several types of LSDs, supporting the idea that LSDs could be seen primarily as "autophagy disorders." C1 [Ballabio, Andrea] Telethon Inst Genet & Med TIGEM, Naples, Italy. [Ballabio, Andrea] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA. [Ballabio, Andrea] Univ Naples Federico II, Dept Pediat, Naples, Italy. [Lieberman, Andrew P.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. [Puertollano, Rosa; Raben, Nina] NIH, Bethesda, MD 20892 USA. [Puertollano, Rosa] NHLBI, Cell Biol Lab, Bethesda, MD USA. [Raben, Nina] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, Bethesda, MD USA. [Slaugenhaupt, Susan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Walkley, Steven U.] Albert Einstein Coll Med, Rose F Kennedy Ctr, Dominick P Purpura Dept Neurosci, Bronx, NY 10467 USA. RP Ballabio, A (reprint author), Telethon Inst Genet & Med TIGEM, Naples, Italy. EM ballabio@tigem.it OI BALLABIO, Andrea/0000-0003-1381-4604 FU NIH [R01 NS063967, HD045561]; NIH, National Heart, Lung, and Blood Institute (NHLBI); Beyond Batten Disease Foundation; Telethon Foundation; European Research Council (ERC) [250154] FX We thank Dr. G. Diez-Roux for manuscript preparation, helpful discussions and critical reading of the manuscript and C. Settembre for critical reading of the manuscript. A. P. L. is supported by the NIH grant R01 NS063967; R. P. is supported by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute (NHLBI); S. U. W. is supported by NIH grant HD045561; A. B. is supported by the Beyond Batten Disease Foundation, the Telethon Foundation and the European Research Council (ERC) grant #250154. NR 132 TC 115 Z9 119 U1 3 U2 21 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD MAY PY 2012 VL 8 IS 5 BP 719 EP 730 DI 10.4161/auto.19469 PG 12 WC Cell Biology SC Cell Biology GA 960QU UT WOS:000305403800002 PM 22647656 ER PT J AU Klucken, J Poehler, AM Ebrahimi-Fakhari, D Schneider, J Nuber, S Rockenstein, E Schlotzer-Schrehardt, U Hyman, BT McLean, PJ Masliah, E Winkler, J AF Klucken, Jochen Poehler, Anne-Maria Ebrahimi-Fakhari, Darius Schneider, Jacqueline Nuber, Silke Rockenstein, Edward Schloetzer-Schrehardt, Ursula Hyman, Bradley T. McLean, Pamela J. Masliah, Eliezer Winkler, Juergen TI Alpha-synuclein aggregation involves a bafilomycin A(1)-sensitive autophagy pathway SO AUTOPHAGY LA English DT Article DE Parkinson disease (PD); dementia with Lewy bodies (DLB); alpha-synuclein; Lewy body; protein aggregation; lysosomal degradation ID CHAPERONE-MEDIATED AUTOPHAGY; LEWY BODY DISEASE; PARKINSONS-DISEASE; IN-VIVO; LYSOSOMAL DEGRADATION; TRANSGENIC MICE; ATPASE ACTIVITY; CELL-DEATH; NEURONS; PROTEIN AB Synucleinopathies like Parkinson disease and dementia with Lewy bodies (DLB) are characterized by alpha-synuclein aggregates within neurons (Lewy bodies) and their processes (Lewy neurites). Whereas alpha-synuclein has been genetically linked to the disease process, the pathological relevance of alpha-synuclein aggregates is still debated. Impaired degradation is considered to result in aggregation of alpha-synuclein. In addition to the ubiquitin-proteasome degradation, the autophagy-lysosomal pathway (ALP) is involved in intracellular degradation processes for alpha-synuclein. Here, we asked if modulation of ALP affects alpha-synuclein aggregation and toxicity. We have identified an induction of the ALP markers LAMP-2A and LC3-II in human brain tissue from DLB patients, in a transgenic mouse model of synucleinopathy, and in a cell culture model for alpha-synuclein aggregation. ALP inhibition using bafilomycin A(1) (BafA1) significantly potentiates toxicity of aggregated alpha-synuclein species in transgenic mice and in cell culture. Surprisingly, increased toxicity is paralleled by reduced aggregation in both in vivo and in vitro models. The dichotomy of effects on aggregating and nonaggregating species of alpha-synuclein was specifically sensitive to BafA1 and could not be reproduced by other ALP inhibitors. The present study expands on the accumulating evidence regarding the function of ALP for alpha-synuclein degradation by isolating an aggregation specific, BafA1-sensitive, ALP-related pathway. Our data also suggest that protein aggregation may represent a detoxifying event rather than being causal for cellular toxicity. C1 [Klucken, Jochen; Poehler, Anne-Maria; Schneider, Jacqueline; Winkler, Juergen] Univ Hosp, Dept Mol Neurol, Erlangen, Germany. [Ebrahimi-Fakhari, Darius; Hyman, Bradley T.; McLean, Pamela J.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Ebrahimi-Fakhari, Darius; Hyman, Bradley T.; McLean, Pamela J.] Harvard Univ, Sch Med, Charlestown, MA USA. [Nuber, Silke; Rockenstein, Edward; Masliah, Eliezer; Winkler, Juergen] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Nuber, Silke] Univ Tubingen Hosp, Dept Med Genet, Tubingen, Germany. [Schloetzer-Schrehardt, Ursula] Univ Hosp, Dept Ophthalmol, Erlangen, Germany. RP Klucken, J (reprint author), Univ Hosp, Dept Mol Neurol, Erlangen, Germany. EM jochen.klucken@uk-erlangen.de OI Ebrahimi-Fakhari, Darius/0000-0002-0026-4714 FU Bavarian State Ministry of Sciences, Research and the Arts (ForNeuroCell); Hamburg Foundation for International Research and Studies; Federal Ministry of Education and Research [01GN0979]; Albert-Raps Foundation; University Hospital, Erlangen [08.11.05.1, TP9]; Bavaria California Technology Center (BaCaTeC); Parkinson's Disease Foundation; NIH [AG5131, NS057096, AG03197, AG10435, AG18440, AG022074, NS038372] FX This study was supported by the Bavarian State Ministry of Sciences, Research and the Arts (ForNeuroCell), Hamburg Foundation for International Research and Studies (fellowship to D. E. F), Federal Ministry of Education and Research (01GN0979), the Albert-Raps Foundation, grants of the University Hospital, Erlangen (ELAN No. 08.11.05.1; IZKF No. TP9), Bavaria California Technology Center (BaCaTeC), Parkinson's Disease Foundation (fellowship to D. E. F.), and the NIH grants (AG5131, NS057096, AG03197, AG10435, AG18440, AG022074 and NS038372. NR 51 TC 37 Z9 37 U1 1 U2 8 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD MAY PY 2012 VL 8 IS 5 BP 754 EP 766 DI 10.4161/auto.19371 PG 13 WC Cell Biology SC Cell Biology GA 960QU UT WOS:000305403800005 PM 22647715 ER PT J AU Canavese, M Santo, L Raje, N AF Canavese, Miriam Santo, Loredana Raje, Noopur TI Cyclin dependent kinases in cancer Potential for therapeutic intervention SO CANCER BIOLOGY & THERAPY LA English DT Review DE cyclin-dependent kinases; cell cycle; CDK inhibitors; multiple myeloma; targeted therapies ID PHASE-I TRIAL; CELL LUNG-CANCER; FLAVOPIRIDOL INDUCES APOPTOSIS; CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIPLE-MYELOMA CELLS; ADVANCED SOLID TUMORS; INHIBITOR FLAVOPIRIDOL; CDK INHIBITORS; SELICICLIB CYC202; DOWN-REGULATION AB Cell cycle progression through each phase is regulated by heterodimers formed by cyclin-dependent kinases (CDKs) and their regulatory partner proteins, the cyclins. Together they coordinate the cellular events through cell cycle. De-regulation of cell cycle control due to aberrant CDK activity is a common feature of most cancer types. Intensive research on small molecules that target cell cycle regulatory proteins has led to the identification of many candidate inhibitors that are able to arrest proliferation and induce apoptosis in neoplastic cells as a promising strategy to treat cancer. Interestingly, cyclin-dependent kinases (CDKs) have also been proposed as therapeutic targets for Multiple Myeloma (MM). Overexpression and aberrant expression of the cyclins, specifically the D cyclins is seen in the majority of MM underscoring the value of exploring CDK inhibition in MM which currently remains an incurable neoplastic plasma-cell disorder. It is characterized by clonal proliferation of malignant plasma cells in the bone marrow micro-environment and associated organ dysfunction. Recent preclinical and early clinical data explore several CDK inhibitors in the context of MM. This review will provide an overview of the main classes of CDK inhibitors with a focus on their mechanism of action and discuss clinical and pharmacological implications of CDK inhibitors as possible therapeutic approaches for the treatment of cancer with specific consideration to MM. C1 [Canavese, Miriam; Santo, Loredana; Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA 02115 USA. RP Raje, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA 02115 USA. EM nraje@partners.org NR 63 TC 61 Z9 63 U1 0 U2 16 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY PY 2012 VL 13 IS 7 BP 451 EP 457 DI 10.4161/cbt.19589 PG 7 WC Oncology SC Oncology GA 940XZ UT WOS:000303927700001 PM 22361734 ER PT J AU Brawner, BM Davis, ZM Fannin, EF Alexander, KA AF Brawner, Bridgette M. Davis, Zupenda M. Fannin, Ehriel F. Alexander, Kamila A. TI Clinical Depression and Condom Use Attitudes and Beliefs Among African American Adolescent Females SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE adolescent females; African American; condom use; depression; HIV; sexual health ID SELF-EFFICACY; RISK BEHAVIOR; SEX PARTNERS; AT-RISK; COMMUNICATION; INTERVENTIONS; PREDICTORS; DISTRESS; VALIDITY; YOUTH AB Depression, HIV, and other sexually transmitted diseases (STDs) are growing concerns among African American adolescent females. Theoretical models contribute to identification of mediators of condom use; however, minimal research has addressed the explicit relationship between clinical depression and condom use in African American adolescent females. The authors report results from quantitative surveys with clinically depressed (n = 64) and nondepressed (n = 64) African American adolescent females in two large metropolitan cities in the eastern United States. Theoretical mediators of condom use in the study sample-attitudes, subjective norms, perceived behavioral control, and intentions-were investigated. Significant differences existed between the groups in condomuse frequency (U = 356.5, p = .037); however, there were no statistically significant differences in condom use attitudes and beliefs. Although clinically depressed and nondepressed African American adolescent females may hold similar attitudes and beliefs about condom use, differences in condom use frequency may be a psychopathologic occurrence. Copyright (C) 2012 Association of Nurses in AIDS Care C1 [Brawner, Bridgette M.; Fannin, Ehriel F.; Alexander, Kamila A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Davis, Zupenda M.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. RP Brawner, BM (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. FU Substance Abuse and Mental Health Services Administration at the American Nurses Association Minority Fellowship Program [5 SM058566-02]; Hampton-Penn Center for Health Disparities Research [NINR P20NR008361]; Fontaine Society Fellowship at the University of Pennsylvania FX This work was supported by funding to Dr. Brawner from the Substance Abuse and Mental Health Services Administration at the American Nurses Association Minority Fellowship Program [5 SM058566-02], the Hampton-Penn Center for Health Disparities Research [NINR P20NR008361], and the Distinguished Postdoctoral Fellowship and the Fontaine Society Fellowship at the University of Pennsylvania. We thank the study participants, their families, and our local community partners for their assistance with this study. NR 31 TC 4 Z9 4 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-3290 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD MAY-JUN PY 2012 VL 23 IS 3 BP 184 EP 194 DI 10.1016/j.jana.2011.03.005 PG 11 WC Nursing SC Nursing GA 183NJ UT WOS:000321822500002 PM 21737313 ER PT J AU Looby, SED AF Looby, Sara E. Dolan TI Menopause-Associated Metabolic Manifestations and Symptomatology in HIV Infection: A Brief Review With Research Implications SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE HIV; menopause; metabolic complications; women ID HUMAN-IMMUNODEFICIENCY-VIRUS; BONE-MINERAL DENSITY; QUALITY-OF-LIFE; CARDIOVASCULAR RISK-FACTORS; ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION; UNINFECTED WOMEN; BODY-COMPOSITION; TRANSITION; DEPRESSION AB Many women living with HIV in the United States have entered or will soon enter menopause. Clinical changes including increased visceral fat, reduced muscle mass, and changes in lipids and bone density are seen across the menopause transition among noninfected women. HIV and antiretroviral therapy use have been associated with similar manifestations, including reduced bone density, and changes in lipid metabolism and body composition. Menopause is also associated with changes in mood, quality of life, and vasomotor symptoms. Similar psychological indices are common among women with HIV, and may worsen during menopause transition. Research investigating the presence and acuity of metabolic, psychological, and vasomotor symptoms among perimenopausal women with HIV is limited. An important, yet unknown consideration for researchers and clinicians is how metabolic and psychological co-morbidities associated with HIV will influence changes associated with menopause in this population. Further research is needed to provide answers to these important questions. Copyright (C) 2012 Association of Nurses in AIDS Care C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, Boston, MA 02115 USA. RP Looby, SED (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, Boston, MA 02115 USA. FU National Institute of Nursing Research [1K23NR011833-01A1] FX Sara E. Dolan Looby's current research is supported by the National Institute of Nursing Research grant # 1K23NR011833-01A1. NR 49 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-3290 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD MAY-JUN PY 2012 VL 23 IS 3 BP 195 EP 203 DI 10.1016/j.jana.2011.06.008 PG 9 WC Nursing SC Nursing GA 183NJ UT WOS:000321822500003 PM 21924646 ER PT J AU Ahalt, C Walter, LC Yourman, L Eng, C Perez-Stable, EJ Smith, AK AF Ahalt, Cyrus Walter, Louise C. Yourman, Lindsey Eng, Catherine Perez-Stable, Eliseo J. Smith, Alexander K. TI "Knowing is Better": Preferences of Diverse Older Adults for Discussing Prognosis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE prognosis; elderly; disability; diverse; PACE ID CANCER-PATIENTS PREFERENCES; OF-LIFE CARE; INFORMATION NEEDS; TERMINAL ILLNESS; MORTALITY; ATTITUDES; COMMUNICATION; END; VALIDATION; DISCLOSURE AB Prognosis is critical in individualizing care for older adults with late life disability. Evidence suggests that preferences for prognostic information may be culturally determined. Yet little is known about the preferences of diverse elders for discussing prognosis. To determine the preferences for discussing prognosis of a diverse sample of older adults with late-life disability We interviewed 60 older adults with mean age 78 and mean 2.5 Activities of Daily Living dependencies. Participants were recruited from San Francisco's On Lok program, the first Program of All-inclusive Care for the Elderly (PACE). Participants were interviewed in English, Spanish, and Cantonese, and responded to scenarios in which their doctors estimated they had 5 years and 1 year left to live. Open-ended questions explored the reasons for their responses. Results were analyzed qualitatively using grounded theory. Sixty-five percent of participants wanted to discuss the prognosis if their doctor estimated they had < 5 years to live and 75% if the estimate was < 1 year. Three themes were prominent among patients who wanted to discuss prognosis: to prepare, to make the most of the life they had left, and to make medical or health-related decisions. Those who preferred not to discuss prognosis described emotional difficulty, the uncertainty of prognosis, or that it would not be useful. Nearly all participants said that doctors should not make assumptions based on race or ethnicity, though differences between ethnic groups emerged. Most patients in this diverse sample of disabled elders were interested in discussing prognosis, while a substantial minority was not. Among those participants who preferred to discuss prognosis, many said that prognostic information would be important as they made difficult medical and personal decisions in late-life. Clinicians should inquire about preferences for discussing prognosis before sharing prognostic estimates. C1 [Ahalt, Cyrus; Walter, Louise C.; Yourman, Lindsey; Smith, Alexander K.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Walter, Louise C.; Yourman, Lindsey; Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Eng, Catherine] Lok Lifeways, San Francisco, CA USA. [Perez-Stable, Eliseo J.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, Med Effectiveness Res Ctr Diverse Populat, San Francisco, CA USA. RP Smith, AK (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. EM aksmith@ucsf.edu.ph FU Center for Aging in Diverse Communities of the Resource Centers for Minority Aging [P30-AG15272]; National Institute on Aging, National Institutes of Health; National Center for Research Resources UCSF-CTSI [UL1 RR024131]; Atlantic Philanthropies; Society of General Internal Medicine; John A. Hartford Foundation; Association of Specialty Professors FX Dr. Smith was supported by a pilot grant from the Center for Aging in Diverse Communities, grant no. P30-AG15272 of the Resource Centers for Minority Aging Research program funded by the National Institute on Aging, National Institutes of Health. Additional support was provided by the National Center for Research Resources UCSF-CTSI (UL1 RR024131), Atlantic Philanthropies, the Society of General Internal Medicine, the John A. Hartford Foundation, and the Association of Specialty Professors. NR 42 TC 24 Z9 24 U1 5 U2 12 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 MAY PY 2012 VL 27 IS 5 BP 568 EP 575 DI 10.1007/s11606-011-1933-0 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 926YM UT WOS:000302869300017 PM 22127798 ER PT J AU Kneeman, JM Misdraji, J Corey, KE AF Kneeman, Jacob M. Misdraji, Joseph Corey, Kathleen E. TI Secondary causes of nonalcoholic fatty liver disease SO THERAPEUTIC ADVANCES IN GASTROENTEROLOGY LA English DT Review DE fatty liver; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; secondary causes AB Nonalcoholic fatty liver disease (NAFLD) is becoming the most common cause of chronic liver disease in the developing world, found in 17-30% of the population in Western countries and 2-4% worldwide. Defined as the accumulation of fatty acid content greater than 5% of liver weight, NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis. The pathophysiology of NAFLD involves increased de novo synthesis of fatty acids in hepatocytes, the retention of lipids due to impaired hepatocyte apolipoprotein secretion or beta-oxidation. The well-known primary causes of NAFLD are obesity, type II diabetes, dyslipidemia, and insulin resistance. However, other less common conditions can cause a similar clinical and histologic picture, and should be considered in patients who present with NAFLD but do not have traditional risk factors. In this review, we discuss uncommon but important causes of NAFLD, including inborn errors of metabolism, iatrogenic causes, viral hepatitis, and nutritional disorders to provide practicing clinicians with an understanding of the less well recognized causes of NAFLD. C1 [Corey, Kathleen E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kneeman, Jacob M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Misdraji, Joseph] Harvard Univ, Sch Med, Boston, MA USA. RP Corey, KE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,BLK 4, Boston, MA 02114 USA. EM kcorey@partners.org NR 41 TC 28 Z9 29 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1756-283X EI 1756-2848 J9 THER ADV GASTROENTER JI Ther. Adv. Gastroenterol. PD MAY PY 2012 VL 5 IS 3 BP 199 EP 207 DI 10.1177/1756283X11430859 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V31ZO UT WOS:000208921700005 PM 22570680 ER PT J AU Tamplin, OJ White, RM Jing, LL Kaufman, CK Lacadie, SA Li, PL Taylor, AM Zon, LI AF Tamplin, Owen J. White, Richard M. Jing, Lili Kaufman, Charles K. Lacadie, Scott A. Li, Pulin Taylor, Alison M. Zon, Leonard I. TI Small molecule screening in zebrafish: swimming in potential drug therapies SO WILEY INTERDISCIPLINARY REVIEWS-DEVELOPMENTAL BIOLOGY LA English DT Article AB Phenotype-driven chemical genetic screens in zebrafish have become a proven approach for both dissection of developmental mechanisms and discovery of potential therapeutics. A library of small molecules can be arrayed into multiwell plates containing zebrafish embryos. The embryo becomes a whole organism in vivo bioassay that can produce a phenotype upon treatment. Screens have been performed that are based simply on the morphology of the embryo. Other screens have scored complex phenotypes using whole mount in situ hybridization, fluorescent transgenic reporters, and even tracking of embryo movement. The availability of many well-characterized zebrafish mutants has also enabled the discovery of chemical suppressors of genetic phenotypes. Importantly, the application of chemical libraries that already contain FDA-approved drugs has allowed the rapid translation of hits from zebrafish chemical screens to clinical trials. (C) 2012 Wiley Periodicals, Inc. C1 [Tamplin, Owen J.; White, Richard M.; Jing, Lili; Kaufman, Charles K.; Lacadie, Scott A.; Li, Pulin; Taylor, Alison M.; Zon, Leonard I.] Harvard Univ, Sch Med, Childrens Hosp Boston,Howard Hughes Med Inst, Harvard Stem Cell Inst,Stem Cell Program, Boston, MA 02115 USA. [Tamplin, Owen J.; White, Richard M.; Jing, Lili; Kaufman, Charles K.; Lacadie, Scott A.; Li, Pulin; Taylor, Alison M.; Zon, Leonard I.] Harvard Univ, Sch Med, Childrens Hosp Boston, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA. [White, Richard M.; Kaufman, Charles K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston,Howard Hughes Med Inst, Harvard Stem Cell Inst,Stem Cell Program, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU Howard Hughes Medical Institute NR 38 TC 19 Z9 19 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1759-7684 EI 1759-7692 J9 WIRES DEV BIOL JI Wiley Interdiscip. Rev.-Dev. Biol. PD MAY-JUN PY 2012 VL 1 IS 3 BP 459 EP 468 DI 10.1002/wdev.37 PG 10 WC Developmental Biology SC Developmental Biology GA V31EP UT WOS:000208867200010 PM 23801494 ER PT J AU Hermes, EDA Wells, TS Smith, B Boyko, EJ Gackstetter, GG Miller, SC Smith, TC AF Hermes, Eric D. A. Wells, Timothy S. Smith, Besa Boyko, Edward J. Gackstetter, Gary G. Miller, Shannon C. Smith, Tyler C. CA Millennium Cohort Study Team TI Smokeless tobacco use related to military deployment, cigarettes and mental health symptoms in a large, prospective cohort study among US service members SO ADDICTION LA English DT Article DE Afghanistan; Iraq war; military personnel; post-traumatic stress disorder; risk factors; smokeless tobacco; tobacco use disorder; veterans; war ID READJUSTMENT RATING-SCALE; MILLENNIUM COHORT; UNITED-STATES; PRIMARY-CARE; FOLLOW-UP; PERSONNEL; SMOKING; PREVALENCE; VALIDATION; STRESS AB Aims To characterize smokeless tobacco initiation and persistence in relation to deployment, combat, occupation, smoking and mental health symptoms. Design Prospective cohort, utilizing self-reported survey data from the Millennium Cohort Study. Setting US military service members in all branches including active duty, reserve and National Guard. Participants Population-based sample of 45 272 participants completing both baseline (July 2001June 2003; n = 77 047) and follow-up (June 2004-January 2006; n = 55 021) questionnaires (follow-up response rate = 71.4%). Measurements Self-reported smokeless tobacco initiation and persistence. Findings Over the study period, 72.4% did not deploy, 13.7% deployed without combat exposures and 13.9% deployed with combat exposures, while 1.9% were smokeless tobacco initiators and 8.9% were persistent users. The odds of initiation were greater for deployers with combat exposure [odds ratio (OR), 1.76; 95% confidence interval (CI), 1.49-2.09], deployers without combat exposure (OR, 1.31; 95% CI, 1.07-1.60) and those who deployed multiple times (OR, 1.67; 95% CI, 1.31-2.14), as well as in smoking recidivists/ initiators (OR, 4.65; 95% CI, 3.82-5.66) and those reporting posttraumatic stress disorder symptoms (OR, 1.54; CI, 1.15-2.07). A similar pattern for higher odds of persistent use was observed for deployment and combat exposure, but not for smoking and mental health symptoms. Military occupation was not significantly associated with initiation or persistence. Conclusions Deployment and combat exposure in the US military are associated with increased risk of smokeless tobacco initiation and persistence while smoking and symptoms of post-traumatic stress disorder increase the odds for initiation. Research is needed on aspects of military service amenable to the reduction or prevention of tobacco consumption. C1 [Hermes, Eric D. A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Wells, Timothy S.; Smith, Besa; Smith, Tyler C.] USN, Dept Deployment Hlth Res, Hlth Res Ctr, San Diego, CA 92152 USA. [Boyko, Edward J.] ERIC, VA Puget Sound, Seattle, WA USA. [Gackstetter, Gary G.] Analyt Serv Inc, Arlington, VA USA. [Miller, Shannon C.] USAF, Res Lab, Wright Patterson AFB, OH 45433 USA. [Miller, Shannon C.] Vet Affairs Med Ctr, Cincinnati, OH 45267 USA. [Miller, Shannon C.] Univ Cincinnati, Ctr Treatment Res & Educ Addict Disorders CeTREAD, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. RP Hermes, EDA (reprint author), Yale Univ, Sch Med, Dept Psychiat, Ste 901,300 George St, New Haven, CT 06511 USA. EM eric.hermes@yale.edu FU US Army Medical Research and Materiel Command, Fort Detrick, Maryland; Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland FX The authors state that they have no financial disclosures or other conflicts of interest in the design, analysis or preparation of this manuscript. The Millennium Cohort Study is funded through the Military Operational Medicine Research Program of the US Army Medical Research and Materiel Command, Fort Detrick, Maryland. The funding organization had no role in the design and conduct of the study; collection, analysis or preparation of data,; or preparation, review or approval of the manuscript.; The Millennium Cohort Study Team includes Gregory C. Gray MD, MPH (College of Public Health and Health Professions, University of Florida, Gainesville, Florida), James R. Riddle DVM, MPH (Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, Ohio), Paul J. Amoroso MD, MPH (Madigan Army Medical Center, Fort Lewis, Washington), Tomoko I. Hooper MD, MPH (Uniformed Services University on the Health Sciences, Bethesda, Maryland) and Margaret A. K. Ryan MD, MPH (US Naval Hospital Camp Pendleton, Camp Pendleton, California). We are indebted to the Millennium Cohort Study participants, without whom these analyses would not be possible. We thank Scott L. SeggermanBS, MS, from the Defense Manpower Data Center, Seaside, California. We also thank the professionals from the US Army Medical Research and Materiel Command, especially those from the Military Operational Medicine Research Program, Fort Detrick, Maryland. We thank Melissa Bagnell MPH; Gina Creaven, MBA; James Davies BS; Gia Gumbs, MPH; Nisara Granado MPH, PhD; Lesley Henry BA; Dennis Hernando BS; Jaime Horton BS; Isabel Jacobson MPH; Kelly Jones MPH; Lauren Kipp BA; Cynthia LeardMann MPH; Travis Leleu BS; Gordon Lynch; Jamie McGrew BS; Hope McMaster PhD; Stacie Nguyen BS; Amanda Pietrucha MPH; Teresa Powell MS; Kari Sausedo MA; Amber Seelig MPH; Beverly Sheppard BS; Katherine Snell BS; Steven Speigle; Marleen Welsh PhD; Martin White MPH; James Whitmer; and CharleneWongMPH; from the Department of Deployment Health Research and Michelle LeWark BA, from the Naval Health Research Center, San Diego, California. We appreciate the support of the Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland. These individuals provided assistance as part of their official duties as employees of the Department of Defense and none received additional financial compensation. The VA Puget Sound provided support for Dr Boyko's participation in this research. NR 49 TC 8 Z9 8 U1 2 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD MAY PY 2012 VL 107 IS 5 BP 983 EP 994 DI 10.1111/j.1360-0443.2011.03737.x PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 919QW UT WOS:000302344500029 PM 22126651 ER PT J AU Hazin, R Lum, F Daoud, YJ AF Hazin, Ribhi Lum, Flora Daoud, Yassine J. TI Ophthalmic features of systemic diseases SO ANNALS OF MEDICINE LA English DT Review DE Congestive heart failure; diabetes; hypertension; nerve palsy; ocular complications of systemic disease; renal failure; retinopathy ID RETINAL MICROVASCULAR ABNORMALITIES; ISCHEMIC OPTIC NEUROPATHY; OBSTRUCTIVE SLEEP-APNEA; FLOPPY EYELID SYNDROME; IDIOPATHIC INTRACRANIAL HYPERTENSION; ATHEROSCLEROSIS RISK; MEDICAL-MANAGEMENT; ARTERY-OCCLUSION; VISUAL-FUNCTION; MACULAR EDEMA AB The eye is intricately integrated with the functions of the body. Ocular changes may precede or run concurrently with various systemic conditions and often represent important prognostic indicators of disease progression. In addition to a thorough diagnostic evaluation and treatment of underlying processes, individuals with systemic diseases and concurrent ocular changes may need comprehensive ophthalmic examination to reduce the risk of visual impairment and morbidity. In this review the authors highlight the clinically relevant ocular signs that occur parallel with systemic conditions. In particular, the study focuses on the varied clinical presentations that can lead to rapid diagnosis to improve management of eye disorders that accompany systemic diseases. C1 [Daoud, Yassine J.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Hazin, Ribhi] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. [Lum, Flora] Amer Acad Ophthalmol, Hoskins Ctr Hlth Policy, Washington, DC USA. RP Daoud, YJ (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. EM ydaoud1@jhmi.edu NR 49 TC 1 Z9 1 U1 0 U2 5 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 J9 ANN MED JI Ann. Med. PD MAY PY 2012 VL 44 IS 3 BP 242 EP 252 DI 10.3109/07853890.2011.572904 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 919JE UT WOS:000302319700005 PM 21568671 ER PT J AU Anderson, J Caplan, L Yazdany, J Robbins, ML Neogi, T Michaud, K Saag, KG O'Dell, JR Kazi, S AF Anderson, Jaclyn Caplan, Liron Yazdany, Jinoos Robbins, Mark L. Neogi, Tuhina Michaud, Kaleb Saag, Kenneth G. O'Dell, James R. Kazi, Salahuddin TI Rheumatoid Arthritis Disease Activity Measures: American College of Rheumatology Recommendations for Use in Clinical Practice SO ARTHRITIS CARE & RESEARCH LA English DT Article ID HEALTH-ASSESSMENT QUESTIONNAIRE; ACUTE-PHASE REACTANTS; LONG-TERM OUTCOMES; ACTIVITY INDEX; ACTIVITY SCORE; ROUTINE ASSESSMENT; 28-JOINT COUNTS; REMISSION; TRIALS; VALIDATION AB Objective Although the systematic measurement of disease activity facilitates clinical decision making in rheumatoid arthritis (RA), no recommendations currently exist on which measures should be applied in clinical practice in the US. The American College of Rheumatology (ACR) convened a Working Group (WG) to comprehensively evaluate the validity, feasibility, and acceptability of available RA disease activity measures and derive recommendations for their use in clinical practice. Methods. The Rheumatoid Arthritis Clinical Disease Activity Measures Working Group conducted a systematic review of the literature to identify RA disease activity measures. Using exclusion criteria, input from an Expert Advisory Panel (EAP), and psychometric analysis, a list of potential measures was created. A survey was administered to rheumatologists soliciting input. The WG used these survey results in conjunction with the psychometric analyses to derive final recommendations. Results. Systematic review of the literature resulted in identification of 63 RA disease activity measures. Application of exclusion criteria and ratings by the EAP narrowed the list to 14 measures for further evaluation. Practicing rheumatologists rated 9 of these 14 measures as most useful and feasible. From these 9 measures, the WG selected 6 with the best psychometric properties for inclusion in the final set of ACR-recommended RA disease activity measures. Conclusion. We recommend the Clinical Disease Activity Index, Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein), Patient Activity Scale (PAS), PAS-II, Routine Assessment of Patient Index Data with 3 measures, and Simplified Disease Activity Index because they are accurate reflections of disease activity; are sensitive to change; discriminate well between low, moderate, and high disease activity states; have remission criteria; and are feasible to perform in clinical settings. C1 [Kazi, Salahuddin] Dallas VA Med Ctr, Dallas, TX 75216 USA. [Saag, Kenneth G.] Univ Alabama, Tuscaloosa, AL 35487 USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Michaud, Kaleb; O'Dell, James R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA. [Neogi, Tuhina] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Robbins, Mark L.] Harvard Vanguard Med Associates, Boston, MA USA. [Yazdany, Jinoos] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Caplan, Liron] Univ Colorado, Sch Med, Denver, CO USA. [Caplan, Liron] Denver VAMC, Denver, CO USA. RP Kazi, S (reprint author), Dallas VA Med Ctr, 4500 S Lancaster Rd 11, Dallas, TX 75216 USA. EM salahuddin.kazi@va.gov OI Anderson, Jaclyn/0000-0002-0893-3900; Neogi, Tuhina/0000-0002-9515-1711 FU Mayo Foundation; Amgen; AstraZeneca; Lilly; Genentech; Merck; Horizon; Sanofi-Aventis; Novartis; Pfizer; Centocor FX Dr. Anderson owns stock and/or stock options in Abbot Laboratories. Dr. Michaud has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from the Mayo Foundation. Dr. Saag has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen, AstraZeneca, Lilly, Genentech, Merck, Horizon, Sanofi-Aventis, Novartis, and Pfizer. Dr. Kazi has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Genentech and Centocor. NR 28 TC 136 Z9 141 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD MAY PY 2012 VL 64 IS 5 BP 640 EP 647 DI 10.1002/acr.21649 PG 8 WC Rheumatology SC Rheumatology GA 918EQ UT WOS:000302232500002 PM 22473918 ER PT J AU Daikh, DI St Clair, EW AF Daikh, David I. St Clair, E. William TI Updated Recommendations for the Treatment of Rheumatoid Arthritis: Another Step on a Long Road SO ARTHRITIS CARE & RESEARCH LA English DT Editorial Material ID T-CELL LYMPHOMA; DISEASE; RISK C1 [Daikh, David I.] Univ Calif San Francisco, Dept Rheumatol, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA. RP Daikh, DI (reprint author), Univ Calif San Francisco, Dept Rheumatol, San Francisco VA Med Ctr, 4150 Clement St,111R, San Francisco, CA 94121 USA. EM david.daikh@ucsf.edu FU NIAID NIH HHS [U19 AI056363] NR 12 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD MAY PY 2012 VL 64 IS 5 BP 648 EP 651 DI 10.1002/acr.21659 PG 4 WC Rheumatology SC Rheumatology GA 918EQ UT WOS:000302232500003 PM 22473919 ER PT J AU Barrera, TL Zeno, D Bush, AL Barber, CR Stanley, MA AF Barrera, Terri L. Zeno, Darrell Bush, Amber L. Barber, Catherine R. Stanley, Melinda A. TI Integrating Religion and Spirituality Into Treatment for Late-Life Anxiety: Three Case Studies SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE religion; spirituality; cognitive behavioral therapy; late-life anxiety; generalized anxiety disorder ID STATE WORRY QUESTIONNAIRE; QUALITY-OF-LIFE; COGNITIVE-BEHAVIORAL THERAPY; OLDER-ADULTS; GERIATRIC ANXIETY; PSYCHOMETRIC PROPERTIES; AFRICAN-AMERICANS; ELDERLY-PATIENTS; PRIMARY-CARE; DISORDER AB Generalized anxiety disorder (GAD) is common in older adults and, although cognitive behavioral therapy (CBT) is an efficacious treatment for late-life GAD, effect sizes are only moderate and attrition rates are high. One way to increase treatment acceptability and enhance current cognitive behavioral treatments for GAD in older adults might be to incorporate religion/spirituality (R/S). The cases presented here illustrate the use of a 12-week modular CBT intervention for late-life anxiety, designed to allow incorporation of R/S elements in accordance with patient preferences. The three women treated using this protocol chose different levels and methods of R/S integration into therapy. All three women showed substantial improvement in worry symptoms, as well as a variety of secondary outcomes following treatment; these gains were maintained at 6-month follow-up. These preliminary results suggest that the incorporation of R/S into CBT might be beneficial for older adults with GAD. Strengths, limitations, and future directions are discussed. C1 [Barrera, Terri L.] Univ Houston, Anxiety Disorder Clin, VA HSR&D Houston Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77204 USA. [Barber, Catherine R.; Stanley, Melinda A.] Baylor Coll Med, Houston, TX 77030 USA. [Barber, Catherine R.] Univ St Thomas, St Paul, MN USA. RP Barrera, TL (reprint author), Univ Houston, Anxiety Disorder Clin, VA HSR&D Houston Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, 126 Heyne Bldg, Houston, TX 77204 USA. EM terri.barrera@gmail.com OI Barrera, Terri/0000-0003-0854-4216 NR 65 TC 6 Z9 7 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD MAY PY 2012 VL 19 IS 2 BP 346 EP 358 PG 13 WC Psychology, Clinical SC Psychology GA 918TV UT WOS:000302274900014 ER PT J AU Keuthen, NJ Sprich, SE AF Keuthen, Nancy J. Sprich, Susan E. TI Utilizing DBT Skills to Augment Traditional CBT for Trichotillomania: An Adult Case Study SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE trichotillomania; hairpulling; dialectical behavior therapy; habit reversal training ID DIALECTICAL BEHAVIOR-THERAPY; BORDERLINE PERSONALITY-DISORDER; EMOTION REGULATION; FUNCTIONAL IMPACT; HABIT REVERSAL; FOLLOW-UP; INVENTORY; SCALE; PHENOMENOLOGY; VALIDATION AB Traditional cognitive-behavioral interventions for trichotillomania have had modest acute treatment outcomes and poor maintenance of gains over time. Techniques adopted from dialectical behavior therapy (DBT) can potentially enhance treatment outcomes by specifically addressing issues of impulsivity, emotion regulation, and distress tolerance. In this paper we discuss the application of a DBT-enhanced treatment and its outcome in a single-case study. C1 [Keuthen, Nancy J.] Harvard Univ, Trichotillomania Clin, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Keuthen, NJ (reprint author), Harvard Univ, Trichotillomania Clin, Massachusetts Gen Hosp, Sch Med, Simches 2,185 Cambridge St, Boston, MA 02114 USA. EM nkeuthen@partners.org NR 36 TC 4 Z9 4 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD MAY PY 2012 VL 19 IS 2 BP 372 EP 380 PG 9 WC Psychology, Clinical SC Psychology GA 918TV UT WOS:000302274900016 ER PT J AU Frakt, AB Pizer, SD Feldman, R AF Frakt, Austin B. Pizer, Steven D. Feldman, Roger TI Should Medicare adopt the Veterans health administration formulary? SO HEALTH ECONOMICS LA English DT Article DE medicare; prescription drugs; demand elasticity; welfare analysis; formulary ID PRESCRIPTION DRUG BENEFIT; DISCRETE-CHOICE MODELS; MARKET SHARE; PART-D; PRICES; INDUSTRY; SENIORS; IMPACT; COST AB Since January 2006 all Medicare beneficiaries have been eligible to obtain outpatient prescription drug coverage through private stand-alone drug plans (PDPs). We estimate a model of beneficiary demand for PDPs and use it to compute the loss of consumer surplus due to tightening PDP formularies to the level found in the Veterans Health Administration (VA). Under a generous assumption of cost savings attributed to increased bargaining leverage associated with exclusion of more drugs from formularies, we find the loss in consumer surplus to be smaller than the financial savings that could be shared between Medicare and beneficiaries. According to our estimates, Medicare beneficiaries could be compensated for the loss in consumer surplus associated with tighter PDP formularies with the savings generated by such formularies. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Frakt, Austin B.; Pizer, Steven D.] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Feldman, Roger] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RP Frakt, AB (reprint author), Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, 150 S Huntington Ave,152H, Boston, MA 02215 USA. EM frakt@bu.edu FU Robert Wood Johnson Foundation's (RWJF's) Changes in Health Care Financing and Organization (HCFO) Initiative [63744]; Health Services Research and Development Service of the Department of Veterans Affairs [IAF 05-042] FX This research was supported by Grant Number 63744 from the Robert Wood Johnson Foundation's (RWJF's) Changes in Health Care Financing and Organization (HCFO) Initiative and by Grant Number IAF 05-042 from the Health Services Research and Development Service of the Department of Veterans Affairs. The views expressed in this article are those of the authors and do not necessarily reflect the positions of the Department of Veterans Affairs, Boston University, the University of Minnesota, or RWJF. NR 45 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9230 J9 HEALTH ECON JI Health Econ. PD MAY PY 2012 VL 21 IS 5 BP 485 EP 495 DI 10.1002/hec.1733 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 917EY UT WOS:000302156500001 PM 21506191 ER PT J AU Raina, D Ahmad, R Rajabi, H Panchamoorthy, G Kharbanda, S Kufe, D AF Raina, Deepak Ahmad, Rehan Rajabi, Hasan Panchamoorthy, Govind Kharbanda, Surender Kufe, Donald TI Targeting cysteine-mediated dimerization of the MUC1-C oncoprotein in human cancer cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE MUC1-C; dimerization; reactive cysteines; oxidation ID DISULFIDE BOND FORMATION; SURVIVAL RESPONSE; OXIDATIVE STRESS; BETA-CATENIN; TRANSCRIPTION FACTOR; CARCINOMA ANTIGEN; REGULATORY LOOP; PROTEIN; ACTIVATION; SUBUNIT AB The MUC1 heterodimeric protein is aberrantly over-expressed in diverse human carcinomas and contributes to the malignant phenotype. The MUC1-C transmembrane subunit contains a CQC motif in the cytoplasmic domain that has be,en implicated in the formation of dimers and in its oncogenic function. The present study demonstrates that MUC1-C forms dimers in human breast and lung cancer cells. MUC1-C dimerization was detectable in the cytoplasm and was independent of MUC1-N, the N-terminal mucin subunit that extends outside the cell. We show that the MUC1-C cytoplasmic domain forms dimers in vitro that are disrupted by reducing agents. Moreover, dimerization of the MUC1-C subunit in cancer cells was blocked by reducing agents and increased by oxidative stress, supporting involvement of the CQC motif in forming disulfide bonds. In support of these observations, mutation of the MUC1-C CQC motif to AQA completely blocked MUC1-C dimerization. Importantly, this study was performed with MUC1-C devoid of fluorescent proteins, such as GFP, CFP and YFP. In this regard, we show that GFP, CFP and YFP themselves form dimers that are readily detectable with cross-linking agents. The present results further demonstrate that a cell-penetrating peptide that targets the MUC1-C CQC cysteines blocks MUC1-C dimerization in cancer cells. These findings provide definitive evidence that: i) the MUC1-C cytoplasmic domain cysteines are necessary and sufficient for MUC1-C dimerization, and ii) these CQC motif cysteines represent an Achilles' heel for targeting MUC1-C function. C1 [Kufe, Donald] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02215 USA. [Raina, Deepak; Panchamoorthy, Govind; Kharbanda, Surender] Genus Oncol, Boston, MA USA. RP Kufe, D (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, 450 Brookline Ave,Dana 830, Boston, MA 02215 USA. EM donald_kufe@dfci.harvard.edu FU National Cancer Institute [CA97098, CA42802, CA100707] FX This work was supported by Grants CA97098, CA42802 and CA100707 awarded by the National Cancer Institute. D.K. holds equity in Genus Oncology and is a consultant to the company. D.R., G.P. and S.K. are employees of Genus Oncology. The other authors disclose no potential conflicts of interest. NR 32 TC 3 Z9 3 U1 0 U2 6 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 2012 VL 40 IS 5 BP 1644 EP + DI 10.3892/ijo.2011.1308 PG 7 WC Oncology SC Oncology GA 918TG UT WOS:000302273400037 ER PT J AU Williams, MT Domanico, J Marques, L Leblanc, NJ Turkheimer, E AF Williams, Monnica T. Domanico, Julian Marques, Luana Leblanc, Nicole J. Turkheimer, Eric TI Barriers to treatment among African Americans with obsessive-compulsive disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE African Americans; Obsessive-compulsive disorder; Barriers to treatment; Health disparities; Ethnic differences ID MENTAL-HEALTH TREATMENT; TREATMENT SEEKING; BEHAVIORAL TREATMENT; SYMPTOMS; ANXIETY; CARE; PARTICIPATION; INDIVIDUALS; RELIABILITY; POPULATION AB African Americans are underrepresented in OCD treatment centers and less likely to experience a remission of symptoms. This study examines the barriers that prevent African Americans with OCD from receiving treatment. Seventy-one adult African Americans with OCD were recruited and administered the modified Barriers to Treatment Participation Scale (BTPS) and the Barriers to Treatment Questionnaire (BTQ). Comparing the BTQ between a European American Internet sample (N = 108) and the African American OCD sample (N = 71) revealed barriers unique to African Americans, including not knowing where to find help and concerns about discrimination. A Mokken Scale Analysis of the BTPS in the African American participants identified seven major barriers, including the cost of treatment, stigma, fears of therapy, believing that the clinician will be unable to help, feeling no need for treatment, and treatment logistics (being too busy or treatment being too inconvenient). Pearson and point-biserial correlations of the scales and demographic and psychological variables were conducted. Significant relationships emerged between age, gender, income, education, insurance status, and ethnic affirmation/belonging among several of the Mokken scales. A one-way ANOVA demonstrated that concerns about cost were significantly greater for those without insurance, versus those with public or private plans. Suggestions for overcoming barriers are presented, including community education, affordable treatment options, and increasing cultural competence among mental health providers. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Williams, Monnica T.] Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA. [Domanico, Julian] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Marques, Luana; Leblanc, Nicole J.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Turkheimer, Eric] Univ Virginia, Dept Psychol, Charlottesville, VA 22904 USA. RP Williams, MT (reprint author), Univ Louisville, Dept Psychol & Brain Sci, 2301 S 3rd St, Louisville, KY 40292 USA. EM m.williams@louisville.edu; juliand@sas.upenn.edu; lmarques@partners.org; njleblanc@partners.org; ent3c@virginia.edu OI Williams, Monnica/0000-0003-0095-3277 FU NIMH NIH HHS [R01 MH045404-17S1, 3 R01 MH045404-17S1, R01 MH045404] NR 53 TC 18 Z9 18 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD MAY PY 2012 VL 26 IS 4 SI SI BP 555 EP 563 DI 10.1016/j.janxdis.2012.02.009 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 920QT UT WOS:000302422800009 PM 22410094 ER PT J AU Zhu, C Morse, LR Battaglino, RA AF Zhu, C. H. Morse, L. R. Battaglino, R. A. TI SNX10 is required for osteoclast formation and resorption activity SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE OSTEOCLAST; BONE RESORPTION; SORTING NEXIN; VESICULAR TRAFFICKING ID VESICULAR TRAFFICKING; SORTING NEXINS; DIFFERENTIATION AB RANKL-stimulation of osteoclast precursors results in up-regulation of genes involved in the process of differentiation and activation. In this report we describe the expression and functional characterization of Sorting Nexin 10 (snx10). Snx10 belongs to the sorting nexin (SNX) family, a diverse group of proteins with a common feature: the PX domain, which is involved in membrane trafficking and cargo sorting in endosomes. Snx10 is strongly up-regulated during RANKL-induced osteoclast differentiation in vitro and expressed in osteoclasts in vivo. qPCR analysis confirmed a significant increase in the expression of snx10 in in vitro-derived osteoclasts, as well as in femur and calvaria. Immunohistochemical analysis of mouse embryo sections showed expression in long bone, calvariae, and developing teeth. The expression was limited to cells that also expressed TRAP, demonstrating osteoclastic localization. Confocal immunofluorescence and subcellular fractionation analysis revealed Snx10 localization in the nucleus and in the endoplasmic reticulum (ER). To study a possible role for snx10 in osteoclast differentiation and function we silenced snx10 expression and found that snx10 silencing inhibited RANKL-induced osteoclast formation and osteoclast resorption on hydroxyapatite. Silencing also inhibited TRAP secretion. Taken together, these results confirm that snx10 is expressed in osteoclasts and is required for osteoclast differentiation and activity in vitro. Since inhibition of vesicular trafficking is essential for osteoclast formation and activity and SNX10 is involved in intracellular vesicular trafficking, these studies may identify a new candidate gene involved in the development of human bone diseases including osteoporosis. J. Cell. Biochem. 113: 16081615, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Zhu, C. H.; Morse, L. R.; Battaglino, R. A.] Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02142 USA. [Morse, L. R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Morse, L. R.] Spaulding Rehabil Hosp, Boston, MA USA. RP Battaglino, RA (reprint author), Forsyth Inst, Dept Cytokine Biol, 245 1st St, Cambridge, MA 02142 USA. EM rbattaglino@forsyth.org RI battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 NR 18 TC 11 Z9 16 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAY PY 2012 VL 113 IS 5 BP 1608 EP 1615 DI 10.1002/jcb.24029 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 908WY UT WOS:000301524900016 PM 22174188 ER PT J AU Darrow, KN Benson, TE Brown, MC AF Darrow, Keith N. Benson, Thane E. Brown, M. Christian TI Planar multipolar cells in the cochlear nucleus project to medial olivocochlear neurons in mouse SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE synapse; reflex; superior olivary complex; descending system ID GUINEA-PIG; HORSERADISH-PEROXIDASE; INFERIOR COLLICULUS; RESPONSE PROPERTIES; BRAIN-STEM; AUDITORY-NERVE; CAT; DORSAL; RAT; EFFERENTS AB Medial olivocochlear (MOC) neurons originate in the superior olivary complex and project to the cochlea, where they act to reduce the effects of noise masking and protect the cochlea from damage. MOC neurons respond to sound via a reflex pathway; however, in this pathway the cochlear nucleus cell type that provides input to MOC neurons is not known. We investigated whether multipolar cells of the ventral cochlear nucleus have projections to MOC neurons by labeling them with injections into the dorsal cochlear nucleus. The projections of one type of labeled multipolar cell, planar neurons, were traced into the ventral nucleus of the trapezoid body, where they were observed terminating on MOC neurons (labeled in some cases by a second cochlear injection of FluoroGold). These terminations formed what appear to be excitatory synapses, i.e., containing small, round vesicles and prominent postsynaptic densities. These data suggest that cochlear nucleus planar multipolar neurons drive the MOC neuron's response to sound. J. Comp. Neurol. 520:13651375, 2012. (c) 2011 Wiley Periodicals, Inc. C1 [Darrow, Keith N.] Worcester State Univ, Dept Commun Sci & Disorders, Worcester, MA 01564 USA. [Darrow, Keith N.; Benson, Thane E.; Brown, M. Christian] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Brown, M. Christian] Harvard Univ, Dept Otol & Laryngol, Sch Med, Boston, MA 02114 USA. RP Darrow, KN (reprint author), Worcester State Univ, Dept Commun Sci & Disorders, Worcester, MA 01564 USA. EM Kdarrow@worcester.edu FU National Institutes of Health-NIDCD [DC01089] FX Grant sponsor: National Institutes of Health-NIDCD; Grant number: DC01089 (to M.C.B.). NR 43 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 1 PY 2012 VL 520 IS 7 BP 1365 EP 1375 DI 10.1002/cne.22797 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 904DG UT WOS:000301173300002 PM 22101968 ER PT J AU Arbiser, JL Bonner, MY Cerulli, R Liu, S Frank, DA AF Arbiser, J. L. Bonner, M. Y. Cerulli, R. Liu, S. Frank, D. A. TI Evidence for a napdh oxidase-stat5 pathway in human melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Arbiser, J. L.; Bonner, M. Y.] Emory Sch Med, Atlanta, GA USA. [Arbiser, J. L.] VAMC Decatur Ga, Dermatol, Atlanta, GA USA. [Cerulli, R.; Liu, S.; Frank, D. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 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 MAY PY 2012 VL 132 SU 1 MA 154 BP S26 EP S26 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900153 ER PT J AU Cheung, E Yao, M Franco, W Purschke, M Tam, J Farinelli, W Wang, Y Anderson, R AF Cheung, E. Yao, M. Franco, W. Purschke, M. Tam, J. Farinelli, W. Wang, Y. Anderson, R. TI Can skin be "copied"?: Assembled full-thickness microscopic skin columns survive, proliferate, and migrate within synthetic matrices in vitro SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Cheung, E.; Yao, M.; Franco, W.; Purschke, M.; Tam, J.; Farinelli, W.; Wang, Y.; Anderson, R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 855 BP S147 EP S147 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900855 ER PT J AU Corey, K Kardos, M Roh, E Kimball, A AF Corey, K. Kardos, M. Roh, E. Kimball, A. TI An analysis of terminology used by primary care physicians to describe concerning lesions referred to an urgent dermatology clinic SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Corey, K.; Kardos, M.; Roh, E.; Kimball, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Corey, K.] Univ Massachusetts, Worcester, MA 01605 USA. [Kardos, M.] Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 284 BP S48 EP S48 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900286 ER PT J AU Dai, I Brooks, Y Dotto, GP AF Dai, I. Brooks, Y. Dotto, G. P. TI The retinoid-related orphan receptor RORalpha functions as a determinant of keratinocyte differentiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Dai, I.; Brooks, Y.; Dotto, G. P.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 376 BP S64 EP S64 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900379 ER PT J AU de Jong, A Cheng, T Huang, S Kasmar, AG Pena-Cruz, V Altman, J Moody, D AF de Jong, A. Cheng, T. Huang, S. Kasmar, A. G. Pena-Cruz, V. Altman, J. Moody, D. TI Lipids from human epidermis can function as antigens for CD1a-restricted T cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [de Jong, A.] Columbia Univ, Med Ctr, New York, NY USA. [Cheng, T.; Huang, S.; Kasmar, A. G.; Moody, D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kasmar, A. G.; Moody, D.] Harvard Univ, Sch Med, Boston, MA USA. [Pena-Cruz, V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Altman, J.] Emory Vaccine Ctr, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 627 BP S106 EP S106 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900628 ER PT J AU Elmariah, SB Reddy, VB Lerner, EA AF Elmariah, S. B. Reddy, V. B. Lerner, E. A. TI Neural recruitment and dynamism in the pathogenesis of atopic dermatitis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Elmariah, S. B.; Reddy, V. B.; Lerner, E. A.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 344 BP S58 EP S58 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900345 ER PT J AU Freeman, EE Tawa, M Dorosario, AA Kupper, TS Fisher, DC AF Freeman, E. E. Tawa, M. Dorosario, A. A. Kupper, T. S. Fisher, D. C. TI Use of brentuximab vedotin for recalcitrant CD30+cutaneous T cell lymphoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Freeman, E. E.] Harvard Dermatol Residency, Boston, MA USA. [Freeman, E. E.; Tawa, M.; Dorosario, A. A.; Kupper, T. S.; Fisher, D. C.] Dana Farber Canc Ctr, Cutaneous Lymphoma Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 556 BP S94 EP S94 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900557 ER PT J AU Geddes, JE Cedeno-Laurent, F Butler, MO Dimitroff, CJ AF Geddes, J. E. Cedeno-Laurent, F. Butler, M. O. Dimitroff, C. J. TI Galectin-1 can bind human melanoma-specific CD8+T cells and trigger immunosuppression SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Geddes, J. E.; Cedeno-Laurent, F.; Dimitroff, C. J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Butler, M. O.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Geddes, J. E.; Cedeno-Laurent, F.; Butler, M. O.; Dimitroff, C. J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 593 BP S101 EP S101 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900596 ER PT J AU Ghazi, ER Kling, MA Propert, K Okawa, J Werth, VP AF Ghazi, E. R. Kling, M. A. Propert, K. Okawa, J. Werth, V. P. TI Increased depression in cutaneous lupus erythematosus compared to the general population and dermatomyositis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Ghazi, E. R.; Kling, M. A.; Okawa, J.; Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Propert, K.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ghazi, E. R.] UMDNJ RWJMS, Piscataway, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 095 BP S16 EP S16 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900094 ER PT J AU Guenova, E Watanabe, R Schlapbach, C Desimone, J Dorosario, A Adams, N Fisher, DC Tawa, M Kupper, TS Clark, RA AF Guenova, E. Watanabe, R. Schlapbach, C. Desimone, J. Dorosario, A. Adams, N. Fisher, D. C. Tawa, M. Kupper, T. S. Clark, R. A. TI Th2 cytokines from malignant T cells suppress benign Th1 responses in patients with L-CTCL SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Harvard Skin Dis Res Ctr, Boston, MA USA. RI Guenova, Emmanuella/A-4656-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 598 BP S102 EP S102 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900599 ER PT J AU Jones, JT Sandsmark, EK Salazar, M Walkosz, BJ Dellavalle, RP AF Jones, J. T. Sandsmark, E. K. Salazar, M. Walkosz, B. J. Dellavalle, R. P. TI Internet survey of tattoo skin care SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Jones, J. T.; Sandsmark, E. K.; Salazar, M.; Dellavalle, R. P.] Univ Colorado, Sch Med, Aurora, CO USA. [Jones, J. T.; Dellavalle, R. P.] Colorado Sch Publ Hlth, Aurora, CO USA. [Walkosz, B. J.] Klein Buendel Inc, Golden, CO USA. [Dellavalle, R. P.] Denver Vet Affairs Med Ctr, Dermatol Serv, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 281 BP S48 EP S48 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900282 ER PT J AU Kang, S Sakamoto, FH Su, M Lomakin, J Akthakul, A Anderson, R Yu, B AF Kang, S. Sakamoto, F. H. Su, M. Lomakin, J. Akthakul, A. Anderson, R. Yu, B. TI Superior barrier function of a novel elastic, skin compatible film resulting from activation of a flowable, polymer emulsion system SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Kang, S.; Su, M.; Lomakin, J.; Akthakul, A.; Yu, B.] Living proof Inc, Skin & New Mat Discovery, Cambridge, MA USA. [Sakamoto, F. H.; Anderson, R.] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 378 BP S64 EP S64 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900380 ER PT J AU Katiyar, SK Jones, V Nandakumar, V AF Katiyar, S. K. Jones, V. Nandakumar, V. TI Green tea catechins reactivate silenced tumor suppressor genes, p16INK4a and Cip1/p21, in UV-irradiated mouse skin and skin tumors by reducing DNA methylation and increasing histone acetylation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Katiyar, S. K.; Jones, V.; Nandakumar, V.] Univ Alabama, Birmingham, AL USA. [Katiyar, S. K.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 677 BP S115 EP S115 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900678 ER PT J AU Lee, KC Weinstock, MA AF Lee, K. C. Weinstock, M. A. TI Association of eyeglasses use with periocular keratinocyte carcinomas and actinic keratosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Lee, K. C.; Weinstock, M. A.] Brown Univ, Providence, RI 02912 USA. [Weinstock, M. A.] US Dept Vet Affairs, Cooperat Studies Program, Washington, DC USA. [Lee, K. C.; Weinstock, M. A.] VA Med Ctr, Providence, RI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 256 BP S43 EP S43 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900257 ER PT J AU Li, W Han, J Chan, AT Qureshi, AA AF Li, W. Han, J. Chan, A. T. Qureshi, A. A. TI Psoriasis and risk of inflammatory bowel disease in US women SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Li, W.; Han, J.; Qureshi, A. A.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Han, J.; Chan, A. T.; Qureshi, A. A.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Han, J.; Chan, A. T.; Qureshi, A. A.] Harvard Univ, Sch Med, Boston, MA USA. [Han, J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chan, A. T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 288 BP S49 EP S49 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900291 ER PT J AU Mann, JA Carlberg, VM Kimball, AB Storrs, FJ Blauvelt, A Simpson, EL AF Mann, J. A. Carlberg, V. M. Kimball, A. B. Storrs, F. J. Blauvelt, A. Simpson, E. L. TI Do we know the cost of dermatologic specialty care? A survey of dermatology providers, residents and patients SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Mann, J. A.; Carlberg, V. M.; Storrs, F. J.; Blauvelt, A.; Simpson, E. L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kimball, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 262 BP S44 EP S44 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900263 ER PT J AU Mattei, PL Donahue, KR Corey, KC Kimball, AB AF Mattei, P. L. Donahue, K. R. Corey, K. C. Kimball, A. B. TI Implementing a system to collect outcome measures for psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Mattei, P. L.; Donahue, K. R.; Corey, K. C.; Kimball, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 276 BP S47 EP S47 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900279 ER PT J AU Morgan, BA AF Morgan, B. A. TI The regulation of dermal papilla cell number to specify hair size SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Morgan, B. A.] Harvard Univ, Sch Med, Boston, MA USA. [Morgan, B. A.] Mass Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 484 BP S82 EP S82 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900486 ER PT J AU Nguyen, K Momtaz, P Kakavand, H Widlund, HR Correll, M Hodi, FS Mihm, MC Thompson, JF Murphy, GF Scolyer, RA Lin, JY AF Nguyen, K. Momtaz, P. Kakavand, H. Widlund, H. R. Correll, M. Hodi, F. S. Mihm, M. C. Thompson, J. F. Murphy, G. F. Scolyer, R. A. Lin, J. Y. TI Distinct gene expression signatures classify desmoplastic and nodular melanomas SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Murphy, G. F.] Brigham & Womens Hosp, Program Dermatopathol, Boston, MA 02115 USA. [Kakavand, H.; Thompson, J. F.; Scolyer, R. A.] Univ Sydney, Sydney, NSW 2006, Australia. [Correll, M.] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Hodi, F. S.; Mihm, M. C.; Lin, J. Y.] Dana Farber Canc Inst, Melanoma Program, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 775 BP S132 EP S132 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900776 ER PT J AU Petukhova, L Ripke, S Becker, T Duvic, M Hordinsky, M Norris, D Price, V Mackay-Wiggan, J Redler, S Chen, WV Amos, CI Lee, A Gregersen, PK Blaumeiser, B Altshuler, D Daly, MJ Nothen, M Betz, R Christiano, AM AF Petukhova, L. Ripke, S. Becker, T. Duvic, M. Hordinsky, M. Norris, D. Price, V. Mackay-Wiggan, J. Redler, S. Chen, W. V. Amos, C. I. Lee, A. Gregersen, P. K. Blaumeiser, B. Altshuler, D. Daly, M. J. Noethen, M. Betz, R. Christiano, A. M. TI Alopecia Areata genome-wide association study SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Petukhova, L.; Mackay-Wiggan, J.; Christiano, A. M.] Columbia Univ, New York, NY USA. [Ripke, S.; Altshuler, D.; Daly, M. J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ripke, S.; Altshuler, D.; Daly, M. J.] Harvard Univ, Sch Med, Boston, MA USA. [Ripke, S.; Altshuler, D.; Daly, M. J.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Becker, T.] Univ Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany. [Becker, T.] German Ctr Neurodegenerat Dis, Bonn, Germany. [Duvic, M.; Chen, W. V.; Amos, C. I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hordinsky, M.] U Minnesota, Dermatol, Minneapolis, MN USA. [Norris, D.] U Colorado, Dermatol, Denver, CO USA. [Price, V.] UCSF, San Francisco, CA USA. [Redler, S.; Noethen, M.; Betz, R.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Lee, A.; Gregersen, P. K.] N Shore LIJHS, Feinstein Inst Med Res, Manhasset, NY USA. [Blaumeiser, B.] Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 432 BP S73 EP S73 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900431 ER PT J AU Tun-Kyi, A Oberholzer, PA Qin, J Karpova, MB Navarini, AA Ungethum, U Dummer, R Dobbeling, U AF Tun-Kyi, A. Oberholzer, P. A. Qin, J. Karpova, M. B. Navarini, A. A. Ungethuem, U. Dummer, R. Doebbeling, U. TI Successful treatment of human cutaneous T cell lymphoma xenografts by potassium antimonyl tartrate SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Tun-Kyi, A.] Harvard Univ, Sch Med, Boston, MA USA. [Oberholzer, P. A.] Broad Inst, Cambridge, MA USA. [Oberholzer, P. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oberholzer, P. A.] Univ Bern, Inselspital, CH-3010 Bern, Switzerland. [Qin, J.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Karpova, M. B.; Navarini, A. A.; Ungethuem, U.; Dummer, R.; Doebbeling, U.] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. RI Navarini, Alexander/C-5504-2014 OI Navarini, Alexander/0000-0001-7059-632X NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 149 BP S25 EP S25 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900150 ER PT J AU Wang, NJ Sanborn, Z Arnett, KL Bayston, LJ Liao, W Proby, CM Leigh, IM Gordon, PB Sharma, M North, JP Vemula, SS Mauro, TM Neuhaus, IM LeBoit, PE Kwok, P Arron, ST Bale, AE Haussler, D Cleaver, JE Gray, JW Spellman, PT South, AP Aster, JC Blacklow, SC Cho, RJ AF Wang, N. J. Sanborn, Z. Arnett, K. L. Bayston, L. J. Liao, W. Proby, C. M. Leigh, I. M. Gordon, P. B. Sharma, M. North, J. P. Vemula, S. S. Mauro, T. M. Neuhaus, I. M. LeBoit, P. E. Kwok, P. Arron, S. T. Bale, A. E. Haussler, D. Cleaver, J. E. Gray, J. W. Spellman, P. T. South, A. P. Aster, J. C. Blacklow, S. C. Cho, R. J. TI Next-generation sequencing identifies Notch receptors as integral tumor suppressors in cutaneous and lung squamous cell carcinomas SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Wang, N. J.; Gray, J. W.; Spellman, P. T.] OHSU, Portland, OR USA. [Sanborn, Z.; Haussler, D.] UCSC, Santa Cruz, CA USA. [Arnett, K. L.; Bayston, L. J.; Leigh, I. M.; Aster, J. C.; Blacklow, S. C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Liao, W.; Sharma, M.; North, J. P.; Mauro, T. M.; Neuhaus, I. M.; Kwok, P.; Arron, S. T.; Cleaver, J. E.; Cho, R. J.] UCSF, San Francisco, CA USA. [Proby, C. M.; South, A. P.] Univ Dundee, Dundee, Scotland. [Gordon, P. B.; Bale, A. E.] Yale, New Haven, CT USA. [Vemula, S. S.; LeBoit, P. E.] San Francisco Dermatopathol Serv, San Francisco, CA USA. [Blacklow, S. C.] Dana Farber, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 135 BP S23 EP S23 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900137 ER PT J AU Watanabe, R Guenova, E Schlapbach, C Tawa, M Desimone, J Adams, N Dorosario, A Fisher, DC Kupper, TS Clark, RA AF Watanabe, R. Guenova, E. Schlapbach, C. Tawa, M. Desimone, J. Adams, N. Dorosario, A. Fisher, D. C. Kupper, T. S. Clark, R. A. TI Mechanisms of resistance of L-CTCL patients to alemtuzumab: What failure can teach us SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Watanabe, R.; Guenova, E.; Schlapbach, C.; Tawa, M.; Desimone, J.; Adams, N.; Dorosario, A.; Fisher, D. C.; Kupper, T. S.; Clark, R. A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RI Guenova, Emmanuella/A-4656-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 053 BP S9 EP S9 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900052 ER PT J AU Wieczorek, IT Propert, KJ Okawa, J Werth, VP AF Wieczorek, I. T. Propert, K. J. Okawa, J. Werth, V. P. TI Progression from cutaneous to systemic lupus erythematosus by ACR criteria usually occurs with mild disease and few systemic symptoms SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 75th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2012 CL Raleigh, NC SP Soc Investigat Dermatol C1 [Wieczorek, I. T.; Okawa, J.; Werth, V. P.] Philadelphia Vet Affairs Med Ctr, Dept Dermatol, Philadelphia, PA USA. [Wieczorek, I. T.; Okawa, J.; Werth, V. P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Propert, K. J.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2012 VL 132 SU 1 MA 264 BP S45 EP S45 PG 1 WC Dermatology SC Dermatology GA 926XV UT WOS:000302866900267 ER PT J AU Kangovi, S Edwards, M Woloszynek, S Mitra, N Feldman, H Kaplan, BS Meyers, KE AF Kangovi, Shreya Edwards, Meredith Woloszynek, Stephen Mitra, Nandita Feldman, Harold Kaplan, Bernard S. Meyers, Kevin E. TI Renin-angiotensin-aldosterone system inhibitors in pediatric focal segmental glomerulosclerosis SO PEDIATRIC NEPHROLOGY LA English DT Article DE Focal segmental glomerulosclerosis; Renin-angiotensin-aldosterone system ID RESISTANT NEPHROTIC SYNDROME; CHILDREN; PROTEINURIA; CREATININE; ENALAPRIL; BLOCKADE; ADULTS AB Conventional immunosuppressive therapy for primary pediatric focal segmental glomerulosclerosis (FSGS) is potentially toxic and only moderate evidence supports its effectiveness. Renin-angiotensin-aldosterone (RAAS) inhibition monotherapy is anecdotally used in selected patients as an alternative to conventional therapy. We performed a retrospective cohort study of children with primary FSGS seen at a tertiary care academic hospital between 1986 and 2008. We classified patients into two groups based upon initial treatment: RAAS inhibition monotherapy (RIM) and conventional therapy (CT). The primary endpoint was progression to end-stage renal disease (ESRD). Secondary endpoints were remission of proteinuria, relapse, and death. The cohort consisted of 67 patients. Mean baseline urine protein/creatinine ratio (Up/c) was 8.0 (5.2, 10.7) mg/mg, and mean baseline estimated glomerular filtration rate (eGFR) was 115.0 (101.8, 128.1) mL/min/1.73 m(2). Patients in the RIM group were more likely to have lower eGFR (100.8 mL/min/1.73 m(2) vs 132.9 mL/min/1.73 m(2), p = 0.01) and less proteinuria (4.4 vs.14.4, p < 0.01). Renal failure occurred in 22.9% of the RIM group vs 40.6% in the CT group (log-rank p = 0.07). After adjustment for African-American race, time period of presentation, baseline age, eGFR, and Up/c, patients in the RIM group had a 0.11 hazard ratio of progressing to renal failure compared with patients in the CT group (p < 0.01). Children treated initially with RIM may have better outcomes than those treated with CT. C1 [Kangovi, Shreya] Philadelphia VA Med Ctr, Robert Wood Johnson VA Clin Scholars Program, Dept Vet Affairs, Philadelphia, PA 19104 USA. [Edwards, Meredith; Woloszynek, Stephen; Kaplan, Bernard S.; Meyers, Kevin E.] Childrens Hosp Philadelphia, Div Nephrol, Philadelphia, PA 19104 USA. [Mitra, Nandita; Feldman, Harold] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Kangovi, S (reprint author), Philadelphia VA Med Ctr, Robert Wood Johnson VA Clin Scholars Program, Dept Vet Affairs, 13th Floor Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kangovi@mail.med.upenn.edu OI Clement, Meredith/0000-0002-0283-6368 NR 15 TC 3 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD MAY PY 2012 VL 27 IS 5 BP 813 EP 819 DI 10.1007/s00467-011-2056-x PG 7 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 918ZG UT WOS:000302289700017 PM 22116578 ER PT J AU Uher, R Perlis, RH Henigsberg, N Zobel, A Rietschel, M Mors, O Hauser, J Dernovsek, MZ Souery, D Bajs, M Maier, W Aitchison, KJ Farmer, A McGuffin, P AF Uher, R. Perlis, R. H. Henigsberg, N. Zobel, A. Rietschel, M. Mors, O. Hauser, J. Dernovsek, M. Z. Souery, D. Bajs, M. Maier, W. Aitchison, K. J. Farmer, A. McGuffin, P. TI Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Antidepressant medication; depressive symptoms; dimensional classification; major depression; outcome prediction ID STAR-ASTERISK-D; SEROTONIN REUPTAKE INHIBITOR; NATIONAL COMORBIDITY SURVEY; MAJOR DEPRESSION; ATYPICAL DEPRESSION; COGNITIVE THERAPY; MODAFINIL AUGMENTATION; MELANCHOLIC FEATURES; UNIPOLAR DEPRESSION; INVENTORY AB Background. Symptom dimensions have not yet been comprehensively tested as predictors of the substantial heterogeneity in outcomes of antidepressant treatment in major depressive disorder. Method. We tested nine symptom dimensions derived from a previously published factor analysis of depression rating scales as predictors of outcome in 811 adults with moderate to severe depression treated with flexibly dosed escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP). The effects of symptom dimensions were tested in mixed-effect regression models that controlled for overall initial depression severity, age, sex and recruitment centre. Significant results were tested for replicability in 3637 adult out-patients with non-psychotic major depression treated with citalopram in level I of Sequenced Treatment Alternatives to Relieve Depression (STAR*D). Results. The interest-activity symptom dimension (reflecting low interest, reduced activity, indecisiveness and lack of enjoyment) at baseline strongly predicted poor treatment outcome in GENDEP, irrespective of overall depression severity, antidepressant type and outcome measure used. The prediction of poor treatment outcome by the interest-activity dimension was robustly replicated in STAR*D, independent of a comprehensive list of baseline covariates. Conclusions. Loss of interest, diminished activity and inability to make decisions predict poor outcome of antidepressant treatment even after adjustment for overall depression severity and other clinical covariates. The prominence of such symptoms may require additional treatment strategies and should be accounted for in future investigations of antidepressant response. C1 [Uher, R.; Aitchison, K. J.; Farmer, A.; McGuffin, P.] Kings Coll London, Inst Psychiat, Genet & Dev Psychiat Ctr, MRC Social, London, England. [Perlis, R. H.] Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Dept Psychiat, Boston, MA 02114 USA. [Perlis, R. H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Henigsberg, N.; Bajs, M.] Univ Zagreb, Sch Med, Croatian Inst Brain Res, Zagreb 41001, Croatia. [Zobel, A.; Maier, W.] Univ Bonn, Dept Psychiat, Bonn, Germany. [Rietschel, M.] Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Mors, O.] Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark. [Hauser, J.] Poznan Univ Med Sci, Dept Psychiat, Lab Psychiat Genet, Poznan, Poland. [Dernovsek, M. Z.] Univ Psychiat Clin, Ljubljana, Slovenia. [Souery, D.] Univ Libre Bruxelles & Psy Pluriel, Ctr Europeen Psychol Med, Lab Psychol Med, Brussels, Belgium. RP Uher, R (reprint author), Inst Psychiat, SGDP, 16 De Crespigny Pk,P080, London SE5 8AF, England. EM rudolf.uher@kcl.ac.uk RI McGuffin, Peter/A-1565-2012; Uher, Rudolf/A-5477-2008; Aitchison, Katherine/G-4476-2013; OI McGuffin, Peter/0000-0002-9888-2907; Uher, Rudolf/0000-0002-2998-0546; Aitchison, Katherine/0000-0002-1107-3024; Henigsberg, Neven/0000-0002-5303-1834 FU European Commission [LSHB-CT-2003-503428]; NIH; National Institute of Mental Health (NIMH) [N01MH90003, MH086026]; Innovative Medicines Initiative of the European Commission [115008]; Proteus Biomedical; Concordant Rater Systems; RIDventures FX The GENDEP project was funded by the European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. Lundbeck provided nortriptyline and escitalopram for the GENDEP study. GlaxoSmithKline and the UK National Institute for Health Research of the Department of Health contributed to the funding of the sample collection at the Institute of Psychiatry, London. The sponsors had no role in the design and conduct of the study, in data collection, analysis, interpretation or writing the report.; Data for the replication study were obtained from the limited access datasets (version 2) distributed from the NIH-supported STAR*D. STAR*D was supported by National Institute of Mental Health (NIMH) Contract no. N01MH90003 to the University of Texas Southwestern Medical Center. The ClinicalTrials.gov identifier is NCT00021528. This manuscript reflects the views of the authors and may not reflect the opinions or views of the STAR*D Study Investigators or the NIH. R. Uher is supported by a grant from the Innovative Medicines Initiative of the European Commission (Grant Agreement no. 115008). R. H. Perlis is supported by NIMH MH086026.; R. H. Perlis has received consulting fees from Proteus Biomedical, Concordant Rater Systems, and RIDventures. N. Henigsberg has participated in clinical trials sponsored by pharmaceutical companies including GlaxoSmithKline and Lundbeck, and has received honoraria for participating in expert panels from pharmaceutical companies including Lundbeck. D. Souery is a member of the national advisory boards for Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly and Lundbeck. K. J. Aitchison is a member of national advisory boards for Bristol-Myer Squibb and Otsuka Pharmaceuticals Limited and has received speaker's bureau honoraria. The other authors have no conflicts of interests to declare. NR 57 TC 58 Z9 58 U1 0 U2 20 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD MAY PY 2012 VL 42 IS 5 BP 967 EP 980 DI 10.1017/S0033291711001905 PG 14 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 920CP UT WOS:000302379800008 PM 21929846 ER PT J AU Bakaeen, FG AF Bakaeen, Faisal G. TI Learning Goals: Expectations of Residents Versus Faculty SO JOURNAL OF SURGICAL RESEARCH LA English DT Editorial Material C1 [Bakaeen, Faisal G.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. [Bakaeen, Faisal G.] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA. RP Bakaeen, FG (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, OCL 112,2002 Holcombe Blvd, Houston, TX 77030 USA. EM fbakaeen@bcm.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY PY 2012 VL 174 IS 1 BP 88 EP 89 DI 10.1016/j.jss.2011.02.010 PG 2 WC Surgery SC Surgery GA 916SK UT WOS:000302123300021 PM 21470633 ER PT J AU Fridman, V David, WS AF Fridman, Vera David, William S. TI Electrodiagnostic Evaluation of Lower Extremity Mononeuropathies SO NEUROLOGIC CLINICS LA English DT Article DE Neuropathy; Nerve conduction studies; Electromyography; Lower extremity ID NEUROPATHIES; FEATURES; NERVE AB This article discusses the anatomy of lower limb mononeuropathies and reviews the general approach to evaluating patients in the electrodiagnostic laboratory with suspected mononeuropathies of the lower limb. Through illustrative cases of patients presenting with a floppy foot, buckling knee, or painful foot, the approaches using nerve conduction studies and needle electromyography are reviewed, and the pattern of findings of peroneal, tibial, sciatic, femoral, and obturator neuropathies is shown. C1 [Fridman, Vera; David, William S.] Massachusetts Gen Hosp, Neuromuscular Diagnost Ctr, Dept Neurol, Boston, MA 02114 USA. [Fridman, Vera; David, William S.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Fridman, V (reprint author), Massachusetts Gen Hosp, Neuromuscular Diagnost Ctr, Dept Neurol, Charles River Plaza,Suite 820,165 Cambridge St, Boston, MA 02114 USA. EM vfridman@partners.org NR 12 TC 1 Z9 1 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD MAY PY 2012 VL 30 IS 2 BP 505 EP + DI 10.1016/j.ncl.2011.12.004 PG 25 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 914YO UT WOS:000301990000006 PM 22361372 ER PT J AU Matos, M Augusto, E Dos Santos-Rodrigues, A Schwarzschild, MA Chen, JF Cunha, RA Agostinho, P AF Matos, Marco Augusto, Elisabete Dos Santos-Rodrigues, Alexandre Schwarzschild, Michael A. Chen, Jiang-Fan Cunha, Rodrigo A. Agostinho, Paula TI Adenosine A(2A) receptors modulate glutamate uptake in cultured astrocytes and gliosomes SO GLIA LA English DT Article DE adenosine A2A receptor; glutamate transporters; astrocytes; gliosomes; GLAST; GLT-I; EAAC1 ID LONG-TERM POTENTIATION; REAL-TIME PCR; AMYLOID-BETA; BRAIN-INJURY; SYNAPTIC-TRANSMISSION; OXIDATIVE STRESS; NERVE-TERMINALS; GLIAL-CELLS; TRANSPORTERS; EXPRESSION AB Glutamate is the primary excitatory neurotransmitter in the central nervous system, where its toxic build-up leads to synaptic dysfunction and excitotoxic cell death that underlies many neurodegenerative diseases. Therefore, efforts have been made to understand the regulation of glutamate transporters, which are responsible for the clearance of extracellular glutamate. We now report that adenosine A2A receptors (A2 AR) control the uptake of D-aspartate in primary cultured astrocytes as well as in an ex vivo preparation enriched in glial plasmalemmal vesicles (gliosomes) from adult rats, whereas A1R and A3R were devoid of effects. Thus, the acute exposure to the A2 AR agonist, CGS 21680, inhibited glutamate uptake, an effect prevented by the A2 AR antagonist, SCH 58261, and abbrogated in cultured astrocytes from A2 AR knockout mice. Furthermore, the prolonged activation of A2 AR lead to a cAMP/protein kinase A-dependent reduction of GLT-I and GLAST mRNA and protein levels, which leads to a sustained decrease of glutamate uptake. This dual mechanism of inhibition of glutamate transporters by astrocytic A2 AR provides a novel candidate mechanism to understand the ability of A2 AR to control synaptic plasticity and neurodegeneration, two conditions tightly associated with the control of extracellular glutamate levels by glutamate transporters. (C) Wiley Periodicals, Inc. C1 [Agostinho, Paula] Univ Coimbra, Fac Med, Inst Biochem, Ctr Neurosci Coimbra, P-3004504 Coimbra, Portugal. [Matos, Marco; Augusto, Elisabete; Dos Santos-Rodrigues, Alexandre; Cunha, Rodrigo A.; Agostinho, Paula] Univ Coimbra, Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, Charlestown, MA USA. [Chen, Jiang-Fan] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Agostinho, P (reprint author), Univ Coimbra, Fac Med, Inst Biochem, Ctr Neurosci Coimbra, P-3004504 Coimbra, Portugal. EM pagost@cnc.cj.uc.pt RI Agostinho, Paula/F-3748-2010; Cunha, Rodrigo/E-7475-2015 OI Agostinho, Paula/0000-0001-5523-4945; Cunha, Rodrigo/0000-0003-2550-6422 FU Portuguese Foundation for Science and Technology (FCT) [PTDC/SAU- NEU/108668/2008]; FCT [SFRH/BD/36289/2007]; NIH [K24NS60991]; DoD [W81XWH-11-1-0150]; CNPq, Brasil [200656/2008-2] FX Grant sponsor: Portuguese Foundation for Science and Technology (FCT); Grant number: PTDC/SAU-NEU/108668/2008; Grant sponsor: FCT Fellowship (M. M.); Grant number: SFRH/BD/36289/2007; Grant sponsor: NIH; Grant number: K24NS60991; Grant sponsor: DoD; Grant number: W81XWH-11-1-0150; Grant sponsor: CNPq, Brasil fellowship (A. S.- R); Grant number: 200656/2008-2. NR 73 TC 49 Z9 49 U1 1 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-1491 J9 GLIA JI Glia PD MAY PY 2012 VL 60 IS 5 BP 702 EP 716 DI 10.1002/glia.22290 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 905PI UT WOS:000301284300002 PM 22298379 ER PT J AU Jiao, X Wood, LD Lindman, M Jones, S Buckhaults, P Polyak, K Sukumar, S Carter, H Kim, D Karchin, R Sjoblom, T AF Jiao, Xiang Wood, Laura D. Lindman, Monica Jones, Sian Buckhaults, Phillip Polyak, Kornelia Sukumar, Saraswati Carter, Hannah Kim, Dewey Karchin, Rachel Sjoblom, Tobias TI Somatic mutations in the notch, NF-KB, PIK3CA, and hedgehog pathways in human breast cancers SO GENES CHROMOSOMES & CANCER LA English DT Article ID COLORECTAL CANCERS; SEQUENCE ALTERATIONS; PROTEIN; BINDING; GENE; IDENTIFICATION; LANDSCAPES; ACTIVATION AB Exome sequencing of human breast cancers has revealed a substantial number of candidate cancer genes with recurring but infrequent somatic mutations. To determine more accurately their mutation prevalence, we performed a mutation analysis of 36 novel candidate cancer genes in 96 human breast cancers. Somatic mutations with potential impact on protein function were observed in the genes ADAM12, CENTB1, CENTG1, DIP2C, GLI1, GRIN2D, HDLBP, IKBKB, KPNA5, NFKB1, NOTCH1, and OTOF. These findings strengthen the evidence for involvement of the Notch, Hedgehog, NF-KB, and PIK3CA pathways in breast cancer development, and point to novel processes that likely are involved. (C) 2012 Wiley Periodicals, Inc. C1 [Jiao, Xiang; Lindman, Monica; Sjoblom, Tobias] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, SE-75185 Uppsala, Sweden. [Wood, Laura D.; Jones, Sian] Sidney Kimmel Canc Ctr, Howard Hughes Med Inst, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD USA. [Buckhaults, Phillip] Univ S Carolina, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. [Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sukumar, Saraswati] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Carter, Hannah; Kim, Dewey; Karchin, Rachel] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. [Carter, Hannah; Kim, Dewey; Karchin, Rachel] Johns Hopkins Univ, Inst Computat Med, Baltimore, MD USA. RP Sjoblom, T (reprint author), Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, SE-75185 Uppsala, Sweden. EM tobias.sjoblom@igp.uu.se RI Karchin, Rachel/A-3385-2010 FU National Institutes of Health [CA43460, CA573445, CA62924, CA121113]; Swedish Cancer Foundation; D.K. Ludwig Fund for Cancer Research FX Supported by: National Institutes of Health, Grant numbers: CA43460, CA573445, CA62924, CA121113; Swedish Cancer Foundation, D.K. Ludwig Fund for Cancer Research. NR 29 TC 28 Z9 29 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 2012 VL 51 IS 5 BP 480 EP 489 DI 10.1002/gcc.21935 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 903LN UT WOS:000301118100008 PM 22302350 ER PT J AU Tomsic, J Liyanarachchi, S Hampel, H Morak, M Thomas, BC Raymond, VM Chittenden, A Schackert, HK Gruber, SB Syngal, S Viel, A Holinski-Feder, E Thibodeau, SN de la Chapelle, A AF Tomsic, Jerneja Liyanarachchi, Sandya Hampel, Heather Morak, Monika Thomas, Brittany C. Raymond, Victoria M. Chittenden, Anu Schackert, Hans K. Gruber, Stephen B. Syngal, Sapna Viel, Alessandra Holinski-Feder, Elke Thibodeau, Stephen N. de la Chapelle, Albert TI An American founder mutation in MLH1 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE MLH1; colon cancer; founder mutation; genetic predisposition ID NONPOLYPOSIS COLORECTAL-CANCER; HEREDITARY COLON-CANCER; LYNCH-SYNDROME; FUNCTIONAL-ANALYSIS; HAPLOTYPE RECONSTRUCTION; MSH2 MUTATION; UNITED-STATES; POPULATION; FAMILIES; GENE AB Mutations in the mismatch repair genes cause Lynch syndrome (LS), conferring high risk of colorectal, endometrial and some other cancers. After the same splice site mutation in the MLH1 gene (c.589-2A>G) had been observed in four ostensibly unrelated American families with typical LS cancers, its occurrence in comprehensive series of LS cases (Mayo Clinic, Germany and Italy) was determined. It occurred in 10 out of 995 LS mutation carriers (1.0%) diagnosed in the Mayo Clinic diagnostic laboratory. It did not occur among 1,803 cases tested for MLH1 mutations by the German HNPCC consortium, while it occurred in three probands and an additional five family members diagnosed in Italy. In the U.S., the splice site mutation occurs on a large (similar to 4.8 Mb) shared haplotype that also harbors the variant c.2146G>A, which predicts a missense change in codon 716 referred to here as V716M. In Italy, it occurs on a different, shorter shared haplotype (similar to 2.2 Mb) that does not carry V716M. The V716M variant was found to be present by itself in the U.S., German and Italian populations with individuals sharing a common haplotype of 280 kb, allowing us to calculate that the variant arose around 5,600 years ago (225 generations; 95% confidence interval 183272). The splice site mutation in America arose or was introduced some 450 years ago (18 generations; 95% confidence interval 1423); it accounts for 1.0% all LS in the Unites States and can be readily screened for. C1 [Tomsic, Jerneja; Liyanarachchi, Sandya; Hampel, Heather; de la Chapelle, Albert] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. [Morak, Monika; Holinski-Feder, Elke] Univ Clin, Med Dept Campus Innenstadt, Munich, Germany. [Morak, Monika; Holinski-Feder, Elke] Ctr Med Genet, MGZ, Munich, Germany. [Thomas, Brittany C.; Thibodeau, Stephen N.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Raymond, Victoria M.; Gruber, Stephen B.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Raymond, Victoria M.; Gruber, Stephen B.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Raymond, Victoria M.; Gruber, Stephen B.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Chittenden, Anu; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Schackert, Hans K.] Tech Univ Dresden, Dept Surg Res, Dresden, Germany. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Viel, Alessandra] Natl Canc Inst, CRO IRCCS, Aviano, Italy. RP de la Chapelle, A (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, 804 Biomed Res Tower,460 W 12th Ave, Columbus, OH 43210 USA. EM albert.delachapelle@osumc.edu FU National Cancer Institute [CA16058, CA67941] FX Grant sponsor: National Cancer Institute; Grant numbers: CA16058, CA67941 NR 34 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2012 VL 130 IS 9 BP 2088 EP 2095 DI 10.1002/ijc.26233 PG 8 WC Oncology SC Oncology GA 897XB UT WOS:000300693100013 PM 21671475 ER PT J AU Gates, MA Xu, MS Chen, WY Kraft, P Hankinson, SE Wolpin, BM AF Gates, Margaret A. Xu, Mousheng Chen, Wendy Y. Kraft, Peter Hankinson, Susan E. Wolpin, Brian M. TI ABO blood group and breast cancer incidence and survival SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE ABO blood group; ABO genotype; blood type; breast cancer; survival ID NATIONAL DEATH INDEX; PANCREATIC-CANCER; GROUP ANTIGENS; PROGNOSTIC FACTORS; RISK; CARCINOMA; EXPRESSION; DISEASE; BENIGN; ASSOCIATION AB ABO blood type has been associated with risk and survival for several malignancies; however, data for an association with breast cancer are inconsistent. Our study population consisted of Nurses' Health Study participants with self-reported serologic blood type and/or ABO genotype. Using Cox proportional hazards regression, we examined the association between serologic blood type and incident breast cancer among 67,697 women, including 3,107 cases. In addition, we examined the association with ABO genotype in a nested case-control study of 1,138 invasive breast cancer cases and 1,090 matched controls. Finally, we evaluated the association between serologic blood type and survival among 2,036 participants with breast cancer. No clear association was seen between serologic blood type or ABO genotype and risk of total breast cancer, invasive breast cancer or breast cancer subtypes. Compared to women with blood type O, the age-adjusted incidence rate ratios for serologic blood type and total breast cancer were 1.06 (95% CI, 0.981.15) for type A, 1.06 (95% CI, 0.931.22) for AB and 1.08 (95% CI, 0.961.20) for B. In genetic analyses, odds ratios for invasive breast cancer were 1.05 (95% CI, 0.871.27) for A/O, 1.21 (95% CI, 0.861.69) for A/A, 0.84 (95% CI, 0.561.26) for A/B, 0.84 (95% CI, 0.631.13) for B/O and 1.17 (95% CI, 0.353.86) for B/B, compared to O/O. No significant association was noted between blood type and overall or breast cancer-specific mortality. Our results suggest no association between ABO blood group and breast cancer risk or survival. C1 [Gates, Margaret A.; Chen, Wendy Y.; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Gates, Margaret A.; Chen, Wendy Y.; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA. [Gates, Margaret A.; Xu, Mousheng; Kraft, Peter; Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chen, Wendy Y.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Gates, MA (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM nhmag@channing.harvard.edu FU National Cancer Institute, National Institutes of Health [P01CA87969, T32CA009001] FX Grant sponsor: National Cancer Institute, National Institutes of Health; Grant numbers: P01CA87969, T32CA009001 NR 48 TC 24 Z9 27 U1 1 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2012 VL 130 IS 9 BP 2129 EP 2137 DI 10.1002/ijc.26220 PG 9 WC Oncology SC Oncology GA 897XB UT WOS:000300693100018 PM 21633955 ER PT J AU Bittner, GD Keating, CP Kane, JR Britt, JM Spaeth, CS Fan, JD Zuzek, A Wilcott, RW Thayer, WP Winograd, JM Gonzalez-Lima, F Schallert, T AF Bittner, G. D. Keating, C. P. Kane, J. R. Britt, J. M. Spaeth, C. S. Fan, J. D. Zuzek, A. Wilcott, R. W. Thayer, W. P. Winograd, J. M. Gonzalez-Lima, F. Schallert, T. TI Rapid, effective, and long-lasting behavioral recovery produced by microsutures, methylene blue, and polyethylene glycol after completely cutting rat sciatic nerves SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE axotomy; nerve regeneration; nerve repair ID WALLERIAN DEGENERATION; MYELINATED AXONS; SEVERED AXONS; NEURITE TRANSECTION; REGENERATION; FUSION; REPAIR; SURVIVAL; NEURONS; INJURY AB Behavioral function lost in mammals (including humans) after peripheral nerve severance is slowly (weeks to years) and often poorly restored by 12-mm/day, nonspecifically directed outgrowths from proximal axonal stumps. To survive, proximal stumps must quickly repair (seal) plasmalemmal damage. We report that, after complete cut- or crush-severance of rat sciatic nerves, morphological continuity, action potential conduction, and behavioral functions can be consistently (>98% of trials), rapidly (minutes to days), dramatically (7085% recovery), and chronically restored and some Wallerian degeneration prevented. We assess axoplasmic and axolemmal continuity by intra-axonal dye diffusion and action potential conduction across the lesion site and amount of behavioral recovery by Sciatic Functional Index and Foot Fault tests. We apply well-specified sequences of solutions containing FDA-approved chemicals. First, severed axonal ends are opened and resealing is prevented by hypotonic Ca2+-free saline containing antioxidants (especially methylene blue) that inhibit plasmalemmal sealing in sciatic nerves in vivo, ex vivo, and in rat B104 hippocampal cells in vitro. Second, a hypotonic solution of polyethylene glycol (PEG) is applied to open closely apposed (by microsutures, if cut) axonal ends to induce their membranes to flow rapidly into each other (PEG-fusion), consistent with data showing that PEG rapidly seals (PEG-seals) transected neurites of B104 cells, independently of any known endogenous sealing mechanism. Third, Ca2+-containing isotonic saline is applied to induce sealing of any remaining plasmalemmal holes by Ca2+-induced accumulation and fusion of vesicles. These and other data suggest that PEG-sealing is neuroprotective, and our PEG-fusion protocols that repair cut- and crush-severed rat nerves might rapidly translate to clinical procedures. (C) 2012 Wiley Periodicals, Inc. C1 [Bittner, G. D.; Fan, J. D.] Univ Texas Austin, Neurobiol Sect, Austin, TX 78712 USA. [Bittner, G. D.; Spaeth, C. S.; Zuzek, A.; Wilcott, R. W.] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA. [Bittner, G. D.; Gonzalez-Lima, F.; Schallert, T.] Univ Texas Austin, Inst Neurosci, Austin, TX 78712 USA. [Keating, C. P.; Winograd, J. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA USA. [Kane, J. R.; Britt, J. M.; Wilcott, R. W.; Gonzalez-Lima, F.; Schallert, T.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Thayer, W. P.] Vanderbilt Univ, Dept Plast Surg, Nashville, TN USA. [Gonzalez-Lima, F.] Univ Texas Austin, Div Pharmacol & Toxicol, Austin, TX 78712 USA. RP Bittner, GD (reprint author), Univ Texas Austin, Neurobiol Sect, Austin, TX 78712 USA. EM bittner@mail.utexas.edu OI Gonzalez-Lima, Francisco/0000-0001-9856-0775 FU Lone Star Paralysis Foundation; Davis Phinney Foundation; NIH FX Contract grant sponsor: Lone Star Paralysis Foundation (to G. D. B.); Contract grant sponsor: Davis Phinney Foundation (to T. S.); Contract grant sponsor: NIH (to F.G.-L.). NR 49 TC 20 Z9 21 U1 1 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY PY 2012 VL 90 IS 5 BP 967 EP 980 DI 10.1002/jnr.23023 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 904ER UT WOS:000301177400006 PM 22302646 ER PT J AU Dutta, T Holliday, PJ Gorski, SM Baharvandy, MS Fernie, GR AF Dutta, Tilak Holliday, Pamela Jean Gorski, Susan Margaret Baharvandy, Mohammad Sadegh Fernie, Geoff Roy TI A biomechanical assessment of floor and overhead lifts using one or two caregivers for patient transfers SO APPLIED ERGONOMICS LA English DT Article DE Patient handling; Patient lifting; Safe patient handling ID HEALTH-CARE WORKERS; MUSCULOSKELETAL INJURY; OCCUPATIONAL INJURY; PERCEIVED EXERTION; ASSISTIVE DEVICES; NURSES; FORCES; RISK; PREVENTION; FACILITIES AB This study investigated the differences in peak external hand forces and external moments generated at the L5/S1 joint of the low back due to maneuvering loaded floor-based and overhead-mounted patient lifting devices using one and two caregivers. Hand forces and external moments at the L5/S1 joint were estimated from ground reaction forces and motion capture data. Caregivers gave ratings col perceived exertion as well as their opinions regarding overhead vs. floor lifts. Use of overhead lifts resulted in significantly lower back loads than floor lifts. Two caregivers working together with a floor lift did not reduce loads on the primary caregiver compared to the single-caregiver case. In contrast, two-caregiver operation of an overhead lift did result in reduced loads compared to the single-caregiver case. Therefore, overhead lifts should be used whenever possible to reduce the risk of back injury to caregivers The use of two caregivers does not compensate for the poorer performance of floor lifts. (C) 2011 Elsevier Ltd and The Ergonomics Society. All rights reserved. C1 [Dutta, Tilak; Holliday, Pamela Jean; Gorski, Susan Margaret; Baharvandy, Mohammad Sadegh; Fernie, Geoff Roy] Toronto Rehabil Inst, Toronto, ON M5G 2A2, Canada. [Dutta, Tilak; Fernie, Geoff Roy] Univ Toronto, Dept Mech & Ind Engn, Toronto, ON, Canada. [Baharvandy, Mohammad Sadegh] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dutta, T (reprint author), Toronto Rehabil Inst, 550 Univ Ave,Suite 12029, Toronto, ON M5G 2A2, Canada. EM tilak.dutta@utoronto.ca; holliday.pam@torontorehab.on.ca; gorski.susan@torontorehab.on.ca; m.baharvandy@alumni.utoronto.ca; fernie.geoff@torontorehab.on.ca FU Workplace Safety and Insurance Board (Ontario); Toronto Rehabilitation Institute; Ministry of Health and Long-Term Care in Ontario (MOHLTC) [06036]; Canada Foundation for Innovation [8708]; Ontario Innovation Trust; Ministry of Research and Innovation; Toronto Rehab Foundation; MITACS; National Science and Engineering Research Council FX This project was funded by a research grant provided by the Workplace Safety and Insurance Board (Ontario). We also acknowledge the support of Toronto Rehabilitation Institute who receives funding under the Provincial Rehabilitation Research Program from the Ministry of Health and Long-Term Care in Ontario (MOHLTC Grant #06036). Equipment was funded in part by Canada Foundation for Innovation (Grant #8708), Ontario Innovation Trust, Ministry of Research and Innovation and Toronto Rehab Foundation. The first author (TD) received funding from the National Science and Engineering Research Council as well as the MITACS Accelerate internship program. The views expressed do not necessarily reflect those of these organizations. NR 53 TC 5 Z9 6 U1 2 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0003-6870 J9 APPL ERGON JI Appl. Ergon. PD MAY PY 2012 VL 43 IS 3 BP 521 EP 531 DI 10.1016/j.apergo.2011.08.006 PG 11 WC Engineering, Industrial; Ergonomics; Psychology, Applied SC Engineering; Psychology GA 890FS UT WOS:000300131100010 PM 21875699 ER PT J AU Waber, DP Queally, JT Catania, L Robaey, P Romero, I Adams, H Alyman, C Jandet-Brunet, C Sallan, SE Silverman, LB AF Waber, Deborah P. Queally, Jennifer Turek Catania, Lori Robaey, Philippe Romero, Ivonne Adams, Heather Alyman, Cheryl Jandet-Brunet, Christine Sallan, Stephen E. Silverman, Lewis B. TI Neuropsychological outcomes of standard risk and high risk patients treated for acute lymphoblastic leukemia on Dana-Farber ALL consortium protocol 95-01 at 5 years post-diagnosis SO PEDIATRIC BLOOD & CANCER LA English DT Article DE acute lymphoblastic leukemia; children; neuropsychological; risk group ID CRANIAL RADIATION-THERAPY; WORKING-MEMORY; DECLARATIVE MEMORY; PROCESSING SPEED; CANCER-INSTITUTE; RANDOMIZED-TRIAL; CHILDREN; CHILDHOOD; ATTENTION; NEUROTOXICITY AB Background Children treated for acute lymphoblastic leukemia (ALL) as High Risk (HR) patients may be more vulnerable to neurocognitive late effects because of the greater intensity of their therapy. We compared neuropsychological outcomes in children treated for Standard Risk (SR) or HR ALL on Dana-Farber Cancer Institute (DFCI) Consortium ALL Protocol 95-01. We also evaluated their performance relative to normative expectations. Procedure. Between 1996 and 2000, 498 children with newly diagnosed ALL were treated on Protocol 95-01, 298 of whom were eligible for neuropsychological follow-up. A feature of this protocol was modification of risk group criteria to treat more children as SR rather than HR patients, intended to minimize toxicities. Testing was completed at a median of 5.3 years post-diagnosis for 211 patients (70.8%; ages 6-25 years; 45.5% male; 40% HR), all of whom were in continuous complete remission. Results. Test scores for both groups were generally at or above normative expectation, with the exception of verbal working memory, processing complex visual information, and parent ratings of metacognitive skills. After adjusting for covariates, the SR group performed better on measures of IQ and academic achievement, working memory and visual learning. Effect sizes, however, were only in the small to moderate range. Conclusions. HR patients exhibited neuropsychological deficits relative to SR patients, though the differences were modest in degree. Modification of the risk group criteria to treat more children on the SR protocol therefore likely afforded some benefit in terms of neurocognitive late effects. Pediatr Blood Cancer 2012;58:758-765. (C) 2011 Wiley Periodicals, Inc. C1 [Waber, Deborah P.; Queally, Jennifer Turek; Catania, Lori] Childrens Hosp, Dept Psychiat, Div Psychol, Boston, MA 02115 USA. [Waber, Deborah P.; Queally, Jennifer Turek; Catania, Lori] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Robaey, Philippe] Univ Montreal, Dept Psychiat, Res Ctr, Ste Justine Hosp, Montreal, PQ H3C 3J7, Canada. [Robaey, Philippe] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. [Romero, Ivonne] Inter Amer Univ, San German, PR USA. [Adams, Heather] Univ Rochester, Med Ctr, Div Child Neurol, Rochester, NY 14642 USA. [Alyman, Cheryl] McMaster Univ, Med Ctr, Div Pediat Hematol Oncol, Hamilton, ON, Canada. [Jandet-Brunet, Christine] CHU Laval, Div Psychol, Dept Pediat Hematol Oncol, Quebec City, PQ G1V 4G2, Canada. [Sallan, Stephen E.; Silverman, Lewis B.] Childrens Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02115 USA. [Sallan, Stephen E.; Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sallan, Stephen E.; Silverman, Lewis B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Waber, DP (reprint author), Childrens Hosp, Dept Psychiat, Div Psychol, Pavil 155,300 Longwood Ave, Boston, MA 02115 USA. EM deborah.waber@childrens.harvard.edu FU National Cancer Institute [2 P01 CA 68484]; Michael J. Garil Fund for Leukemia Research; National Institute of Child Health and Development [P30-HD18655] FX Grant sponsor: National Cancer Institute; Grant number: 2 P01 CA 68484; Grant sponsor: Michael J. Garil Fund for Leukemia Research; Grant sponsor: National Institute of Child Health and Development; Grant number: P30-HD18655. NR 34 TC 10 Z9 11 U1 0 U2 4 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2012 VL 58 IS 5 BP 758 EP 765 DI 10.1002/pbc.23234 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 901RM UT WOS:000300984500017 PM 21721112 ER PT J AU Yu, J Taylor, L Rich, C Toselli, P Stone, P Green, D Warburton, R Hill, N Goldstein, R Polgar, P AF Yu, Jun Taylor, Linda Rich, Celeste Toselli, Paul Stone, Philip Green, Daniel Warburton, Rod Hill, Nicholas Goldstein, Ronald Polgar, Peter TI Transgenic expression of an altered angiotensin type I AT1 receptor resulting in marked modulation of vascular type I collagen SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; BRADYKININ B2 RECEPTOR; HUMAN LUNG FIBROBLASTS; SIGNAL-TRANSDUCTION; MESANGIAL CELLS; INTRACELLULAR LOOP; ACTIVATION; PATHWAY; MUTANT; PHOSPHORYLATION AB The angiotensin II (AngII) type I receptor (AT1) was modified by replacing its third intracellular loop and C-terminal tail with the corresponding regions from the bradykinin B2 receptor. Transgenic mice were produced that overexpress this mutated receptor (AB3T). Considerably less collagen content in the intact aorta and in primary aortic smooth muscle cells (aSMCs) cultures was observed in the transgenic mice. On the other hand, elastin content remained unchanged as measured by Western blot, and insoluble amino acid quantitation. The contraction of isolated aortas also remained unaltered. The aSMCs derived from the transgenic mice showed a reduction in AngII responsive type I collagen production. In aSMCs from transgenic mice, the cascade of Akt to the mammalian target rapamycin (mTOR) to p70 S6 kinase (p70S6K) was not AngII activated, while in the aSMCs from wild-type (WT) mice the cascade was AngII activated. Angiotensin activation of Smad2 and Stat3 was also reduced in the AB3T aSMCs. However, no change in the effect of transforming growth factor beta (TGF beta) on type I collagen production was observed. Also, the activation of ERK and JNK and G-protein linked signaling remained unaltered in response to AngII. Akt and PI3K activation inhibitors blocked AngII-stimulated type I collagen expression in WT aSMCs, whereas ERK inhibitor had no such effect. Our results point to an Akt/mTOR/p70S6K regulation of collagen production by AngII with participation of Smad2 and Stat3 cascades in this process. J. Cell. Physiol. 227: 2013-2021, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Yu, Jun; Taylor, Linda; Rich, Celeste; Toselli, Paul; Stone, Philip; Polgar, Peter] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Green, Daniel] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. [Warburton, Rod; Hill, Nicholas] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Warburton, Rod; Hill, Nicholas] Tufts Med Ctr, Div Pulm & Crit Care, Dept Med, Tupper Res Inst, Boston, MA USA. [Goldstein, Ronald] VA Boston Healthcare Syst, Boston, MA USA. RP Polgar, P (reprint author), Boston Univ, Sch Med, Dept Biochem, 72 E Concord St,K406, Boston, MA 02118 USA. EM peterp@bu.edu OI Yu, Jun/0000-0002-7750-6419; Polgar, Peter/0000-0002-9112-1101 FU National Heart, Lung, and Blood Institute; National Institutes of Health [HL025776] FX Contract grant sponsor: National Heart, Lung, and Blood Institute.; Contract grant sponsor: National Institutes of Health;; Contract grant number: HL025776. NR 26 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 2012 VL 227 IS 5 BP 2013 EP 2021 DI 10.1002/jcp.22929 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 879ZS UT WOS:000299373900026 PM 21751211 ER PT J AU Raza, A Galili, N Mulford, D Smith, SE Brown, GL Steensma, DP Lyons, RM Boccia, R Sekeres, MA Garcia-Manero, G Mesa, RA AF Raza, Azra Galili, Naomi Mulford, Deborah Smith, Scott E. Brown, Gail L. Steensma, David P. Lyons, Roger M. Boccia, Ralph Sekeres, Mikkael A. Garcia-Manero, Guillermo Mesa, Ruben A. TI Phase 1 dose-ranging study of ezatiostat hydrochloride in combination with lenalidomide in patients with non-deletion (5q) low to intermediate-1 risk myelodysplastic syndrome (MDS) SO JOURNAL OF HEMATOLOGY & ONCOLOGY LA English DT Article DE MDS; Ezatiostat; Lenalidomide; Phase 1; Non-deletion (5q) ID INTERNATIONAL WORKING GROUP; RESPONSE CRITERIA; DELETION AB Background: Ezatiostat, a glutathione S-transferase P1-1 inhibitor, promotes the maturation of hematopoietic progenitors and induces apoptosis in cancer cells. Results: Ezatiostat was administered to 19 patients with non-deletion(5q) myelodysplastic syndrome (MDS) at one of two doses (2000 mg or 2500 mg/day) in combination with 10 mg of lenalidomide on days 1-21 of a 28-day cycle. No unexpected toxicities occurred and the incidence and severity of adverse events (AEs) were consistent with that expected for each drug alone. The most common non-hematologic AEs related to ezatiostat in combination with lenalidomide were mostly grade 1 and 2 fatigue, anorexia, nausea, diarrhea, and vomiting; hematologic AEs due to lenalidomide were thrombocytopenia, neutropenia, and anemia. One of 4 evaluable patients (25%) in the 2500/10 mg dose group experienced an erythroid hematologic improvement (HI-E) response by 2006 MDS International Working Group (IWG) criteria. Four of 10 evaluable patients (40%) in the 2000 mg/10 mg dose group experienced an HI-E response. Three of 7 (43%) red blood cell (RBC) transfusion-dependent patients became RBC transfusion independent, including one patient for whom prior lenalidomide monotherapy was ineffective. Three of 5 (60%) thrombocytopenic patients had an HI-platelet (HI-P) response. Bilineage HI-E and HI-P responses occurred in 3 of 5 (60%), 1 of 3 with HI-E and HI-N (33%), and 1 of 3 with HI-N and HI-P (33%). One of 3 patients (33%) with pancytopenia experienced a complete trilineage response. All multilineage responses were observed in the 2000/10 mg doses recommended for future studies. Conclusions: The tolerability and activity profile of ezatiostat co-administered with lenalidomide supports the further development of ezatiostat in combination with lenalidomide in MDS and also encourages studies of this combination in other hematologic malignancies where lenalidomide is active. C1 [Raza, Azra; Galili, Naomi] Columbia Univ Med Ctr, New York, NY USA. [Mulford, Deborah] Univ Rochester, Rochester, NY USA. [Smith, Scott E.] Loyola Univ Chicago Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL USA. [Brown, Gail L.] Telik Inc, Palo Alto, CA USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lyons, Roger M.] Canc Care Ctr S Texas US Oncol, San Antonio, TX USA. [Boccia, Ralph] Ctr Canc & Blood Disorders, Bethesda, MD USA. [Sekeres, Mikkael A.] Cleveland Clin Taussig Canc Inst, Cleveland, OH USA. [Mesa, Ruben A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Mesa, Ruben A.] Mayo Clin, Scottsdale, AZ USA. RP Raza, A (reprint author), Columbia Univ Med Ctr, New York, NY USA. EM azra.raza@columbia.edu OI Steensma, David/0000-0001-5130-9284 FU Telik, Inc., Palo Alto, California, USA FX This work was supported by Telik, Inc., Palo Alto, California, USA. NR 17 TC 7 Z9 7 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8722 J9 J HEMATOL ONCOL JI J. Hematol. Oncol. PD APR 30 PY 2012 VL 5 AR 18 DI 10.1186/1756-8722-5-18 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 987DQ UT WOS:000307397100001 PM 22546242 ER PT J AU Makris, N Seidman, LJ Brown, A Valera, EM Kaiser, JR Petty, CR Liang, LC Aleardi, M Boriel, D Henderson, CS Giddens, M Faraone, SV Spencer, TJ Biederman, J AF Makris, Nikos Seidman, Larry J. Brown, Ariel Valera, Eve M. Kaiser, Jonathan R. Petty, Carter R. Liang, Lichen Aleardi, Megan Boriel, Denise Henderson, Carly S. Giddens, Michelle Faraone, Stephen V. Spencer, Thomas J. Biederman, Joseph TI Further understanding of the comorbidity between attention-deficit/hyperactivity disorder and bipolar disorder in adults: An MRI study of cortical thickness SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE ADHD; BPD; Comorbidity; Cortical thickness; MRI ID DEFICIT HYPERACTIVITY DISORDER; ANTERIOR PREFRONTAL CORTEX; HUMAN CEREBRAL-CORTEX; HUMAN COGNITION; HUMAN BRAIN; MEMORY; ABNORMALITIES; SEGMENTATION; LOCALIZATION; ADOLESCENTS AB Although Attention-Deficit/Hyperactivity Disorder (ADHD) and Bipolar Disorder (BPD) frequently co-occur and represent a particularly morbid clinical form of both disorders, neuroimaging research addressing this comorbidity is scarce. Our aim was to evaluate cortical thickness in ADHD and BPD, testing the hypothesis that comorbid subjects (ADHD+BPD) would have neuroanatomical correlates of both disorders. Magnetic Resonance Imaging (MRI) findings were compared between 31 adults with ADHD + BPD, 18 with BPD, 26 with ADHD, and 23 healthy controls. Cortical thickness analysis of regions of interest was estimated as a function of ADHD and BPD status, using linear regression models. BPD was associated with significantly thicker cortices in 13 regions, independently of ADHD status and ADHD was associated with significantly thinner neocortical gray matter in 28 regions, independent of BPD. In the comorbid state of ADHD plus BPD, the profile of cortical abnormalities consisted of structures that are altered in both disorders individually. Results support the hypothesis that ADHD and BPD independently contribute to cortical thickness alterations of selective and distinct brain structures, and that the comorbid state represents a combinatory effect of the two. Attention to comorbidity is necessary to help clarify the heterogeneous neuroanatomy of both BPD and ADHD. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Makris, Nikos; Kaiser, Jonathan R.; Liang, Lichen; Boriel, Denise; Giddens, Michelle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Morphometr Anal,Dept Psychiat, Boston, MA 02129 USA. [Makris, Nikos; Seidman, Larry J.; Valera, Eve M.; Giddens, Michelle] MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Makris, Nikos; Kaiser, Jonathan R.; Liang, Lichen; Boriel, Denise; Giddens, Michelle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Morphometr Anal,Dept Neurol, Boston, MA 02129 USA. [Seidman, Larry J.; Brown, Ariel; Valera, Eve M.; Petty, Carter R.; Aleardi, Megan; Henderson, Carly S.; Spencer, Thomas J.; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Seidman, Larry J.] Harvard Univ, Massachusetts Mental Hlth Ctr,Med Sch, Beth Israel Deaconess Med Ctr, Publ Psychiat Div,Dept Psychiat, Boston, MA 02115 USA. [Brown, Ariel] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02118 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), 55 Fruit St,Yawkey 6A, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH [MH 62152, 1R21MH084041-01A1, F32 MH065040-01A1]; National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award; NIDA [1R01DA027804-01]; ARRA-NIH-NCCAM; Janssen Pharmaceuticals; Johnson and Johnson Center for the Study of Psychopathology; Fairway Trust; Harvard Medical School Department of Psychiatry; Clinical Research Training Program Fellowship in Biological and Social Psychiatry [MH-16259]; National Center for Research Resources [P41RR14075]; March of Dimes Foundation; Mental Illness and Neuroscience Discovery (MIND) Institute (US) FX The authors would like to thank Sharmila Bandyopadhyay, Katherine Crum, Kalika Kelkar, Alexandra Lomedico, Snezana Milanovic, Michael Monuteaux, Michael Schiller, Heidi Thermenos, Michael Vitulano, and our research study volunteers for their generous assistance. This research was primarily supported by a grant from the NIMH MH 62152 (LJS) and the National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award (JB). Preparation of this article was also supported in part by grants from: NIDA 1R01DA027804-01, NIMH 1R21MH084041-01A1, ARRA-NIH-NCCAM (NM); the Janssen Pharmaceuticals and the Johnson and Johnson Center for the Study of Psychopathology (JB); the Fairway Trust (DK); the National Research Service Award (NIMH F32 MH065040-01A1), the Peter Livingston Fellowship through the Harvard Medical School Department of Psychiatry, and the Clinical Research Training Program Fellowship in Biological and Social Psychiatry MH-16259 (EMV); The National Center for Research Resources (P41RR14075); the March of Dimes Foundation (LJS), and the Mental Illness and Neuroscience Discovery (MIND) Institute (LJS). NR 41 TC 8 Z9 9 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 30 PY 2012 VL 202 IS 1 BP 1 EP 11 DI 10.1016/j.pscychresns.2011.11.003 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 976YD UT WOS:000306622400001 PM 22640688 ER PT J AU Bateman, BT Shaw, KM Kuklina, EV Callaghan, WM Seely, EW Hernandez-Diaz, S AF Bateman, Brian T. Shaw, Kate M. Kuklina, Elena V. Callaghan, William M. Seely, Ellen W. Hernandez-Diaz, Sonia TI Hypertension in Women of Reproductive Age in the United States: NHANES 1999-2008 SO PLOS ONE LA English DT Article ID ANTIHYPERTENSIVE MEDICATION USE; MAJOR CONGENITAL-MALFORMATIONS; RISK-FACTORS; CHILDBEARING AGE; EARLY-PREGNANCY; PREVALENCE; DISPARITIES; TRENDS; US; DISORDERS AB Objective: To examine the epidemiology of hypertension in women of reproductive age. Methods: Using NHANES from 1999-2008, we identified 5,521 women age 20-44 years old. Hypertension status was determined using blood pressure measurements and/or self-reported medication use. Results: The estimated prevalence of hypertension in women of reproductive age was 7.7% (95% confidence interval (CI): 6.9%-8.5%). The prevalence of anti-hypertensive pharmacologic therapy was 4.2% (95% CI 3.5%-4.9%). The prevalence of hypertension was relatively stable across the study period; the age and race adjusted odds of hypertension in 2007-2008 did not differ significantly from 1999-2000 (odds ratio 1.2, CI 0.8 to 1.7, p = 0.45). Significant independent risk factors associated with hypertension included older age, non-Hispanic black race (compared to non-Hispanic whites), diabetes mellitus, chronic kidney disease, and higher body mass index. The most commonly used antihypertensive medications included diuretics, angiotensin-converting enzyme inhibitors (ACE), and beta blockers. Conclusion: Hypertension occurs in about 8% of women of reproductive age. There are remarkable differences in the prevalence of hypertension between racial/ethnic groups. Obesity is a risk factor of particular importance in this population because it affects over 30% of young women in the U. S., is associated with more than 4 fold increased risk of hypertension, and is potentially modifiable. C1 [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Div Obstet Anesthesia, Sch Med,Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Shaw, Kate M.; Kuklina, Elena V.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Callaghan, William M.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Seely, Ellen W.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Bateman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Obstet Anesthesia, Sch Med,Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. EM BBateman@partners.org FU National Institutes of Health [GM007592] FX This work was supported by National Institutes of Health T32 training grant GM007592 (BTB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 23 Z9 24 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 30 PY 2012 VL 7 IS 4 AR e36171 DI 10.1371/journal.pone.0036171 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UL UT WOS:000305340200047 PM 22558371 ER PT J AU Pho, MT Swaminathan, S Kumarasamy, N Losina, E Ponnuraja, C Uhler, LM Scott, CA Mayer, KH Freedberg, KA Walensky, RP AF Pho, Mai T. Swaminathan, Soumya Kumarasamy, Nagalingeswaran Losina, Elena Ponnuraja, C. Uhler, Lauren M. Scott, Callie A. Mayer, Kenneth H. Freedberg, Kenneth A. Walensky, Rochelle P. TI The Cost-Effectiveness of Tuberculosis Preventive Therapy for HIV-Infected Individuals in Southern India: A Trial-Based Analysis SO PLOS ONE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; SUB-SAHARAN AFRICA; OBSERVATIONAL DATABASE; COTE-DIVOIRE; ADULTS; RISK; DISEASE; COHORT; COUNTRIES; CRITERIA AB Background: Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India. Methods: We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm(3), and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH). Results: Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of $100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of $55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence. Conclusions: Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care. C1 [Pho, Mai T.] Univ Chicago, Med Ctr, Dept Med, Sect Hosp Med, Chicago, IL 60637 USA. [Swaminathan, Soumya; Ponnuraja, C.] Natl Inst Res TB, Chennai, Tamil Nadu, India. [Kumarasamy, Nagalingeswaran] VHS, YR Gaitonde Ctr AIDS Res & Educ, Chennai, Tamil Nadu, India. [Uhler, Lauren M.; Scott, Callie A.; Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Providence, RI USA. RP Pho, MT (reprint author), Univ Chicago, Med Ctr, Dept Med, Sect Hosp Med, Chicago, IL 60637 USA. EM mpho@medicine.bsd.uchicago.edu; rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy And Infectious Diseases [T32 AI07433, R01-AI058736, K24-AI062476, K24-AR057827]; National Institute of Health - Fogarty International Center [D43-TW000237]; Indian Council of Medical Research; WHO/USAID (Model DOTS Project) FX This work was supported by the National Institute of Allergy And Infectious Diseases award numbers [T32 AI07433, R01-AI058736, K24-AI062476, and K24-AR057827]; the National Institute of Health - Fogarty International Center [D43-TW000237]; the Indian Council of Medical Research; and the WHO/USAID (Model DOTS Project). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 6 Z9 6 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 30 PY 2012 VL 7 IS 4 AR e36001 DI 10.1371/journal.pone.0036001 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UL UT WOS:000305340200034 PM 22558301 ER PT J AU Sher, L Stanley, BH Posner, K Arendt, M Grunebaum, MF Neria, Y Mann, JJ Oquendo, MA AF Sher, Leo Stanley, Barbara H. Posner, Kelly Arendt, Mikkel Grunebaum, Michael F. Neria, Yuval Mann, Joseph John Oquendo, Maria A. TI Decreased suicidal ideation in depressed patients with or without comorbid posttraumatic stress disorder treated with selective serotonin reuptake inhibitors: An open study SO PSYCHIATRY RESEARCH LA English DT Article DE Posttraumatic stress disorder; Major depressive disorder; Suicidal ideation; Selective serotonin reuptake inhibitors ID BORDERLINE PERSONALITY-DISORDER; MAJOR DEPRESSION; DOUBLE-BLIND; PSYCHIATRIC OUTPATIENTS; CLINICAL-FEATURES; ANXIETY DISORDERS; MOOD DISORDER; WAR VETERANS; PTSD; PLACEBO AB Comorbidity of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) is associated with higher morbidity including suicidal ideation and behavior. Selective serotonin reuptake inhibitors (SSRIs) are a known treatment for PTSD, MOD and comorbid PTSD and MDD. Since the patients with comorbid MOD and PTSD (PTSD-MDD) are sicker, we hypothesize a poorer response to treatment compared to patients with MOD only. Ninety-six MDD patients were included in the study: 76 with MDD only and 20 with PTSD-MDD. Demographic and clinical parameters at baseline were assessed. We examined clinical parameters before and after 3 months of open SSRI treatment in subjects with PTSD-MDD and compared this group to individuals with MDD only. At baseline, PTSD-MDD patients had higher Hamilton Depression Rating Scale and Buss-Durkee Hostility Scale scores compared with MOD only subjects. There was a significant decrease in scores on the Hamilton Depression Rating Scale, Beck Depression Inventory, Beck Hopelessness Scale, and Beck Scale for Suicidal Ideation after 3 months of treatment with SSRIs in both groups. The magnitude of improvement in Beck Scale for Suicidal Ideation scores was greater in the PTSD-MDD group compared to the MDD only subjects. Symptoms of depression including suicidal ideation improved in MDD patients with or without comorbid PTSD after 3 months of treatment with SSRIs but improvement in suicidal ideation was greater in the PTSD-MDD group. Our finding has not supported the hypothesis that a response to treatment is poorer in the PTSD-MDD group which may indicate that sicker patients benefit more from the treatment. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, MHPCC, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu RI Stanley, Barbara/J-8736-2013 FU Conte Center for the Neurobiology of Mental Disorders [5 P50 MH62185, MH48514, MH59710, AA15630]; Nina Rahn Fund FX This study was supported by the Conte Center for the Neurobiology of Mental Disorders (5 P50 MH62185), MH48514, MH59710, AA15630, and the Nina Rahn Fund. NR 63 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 30 PY 2012 VL 196 IS 2-3 BP 261 EP 266 DI 10.1016/j.psychres.2011.11.010 PG 6 WC Psychiatry SC Psychiatry GA 962MG UT WOS:000305548600016 PM 22397913 ER PT J AU Gros, DF Price, M Magruder, KM Frueh, BC AF Gros, Daniel F. Price, Matthew Magruder, Kathryn M. Frueh, B. Christopher TI Symptom overlap in posttraumatic stress disorder and major depression SO PSYCHIATRY RESEARCH LA English DT Article DE Posttraumatic stress disorder; Major depressive disorder; Comorbidity; Transdiagnostic treatment; Hybrid models of psychopathology ID PRIMARY-CARE CLINICS; ADMINISTERED PTSD SCALE; DSM-IV ANXIETY; PSYCHOMETRIC PROPERTIES; MOOD DISORDERS; VETERANS; COMORBIDITY; PSYCHOPATHOLOGY; CLASSIFICATION; PREVALENCE AB Over the past decade there has been consistent criticism of the diagnostic criteria of posttraumatic stress disorder (PTSD) because of its high comorbidity with other mental disorders. Part of the problem surrounding PTSD may be related to the heterogeneity of its symptoms. In fact, recent research has identified a subset of PTSD symptoms, including symptoms of numbing and dysphoria, that may explain much of the overlap between PTSD and major depressive disorder (MDD). The present study sought to extend prior work by investigating the various subsets of PTSD symptoms in individuals from all four diagnostic combinations of PTSD and MDD (no MDD-PTSD, MDD-only, PTSD-only, and comorbid MDD-PTSD). Consenting participants completed diagnostic interviews and were categorized into the four groups. Based on responses to a self-report measure of PTSD symptoms, participants with no MDD-PTSD reported the least severe symptoms while the participants with comorbid MDD-PTSD reported the most severe symptoms. Interesting, participants in the MDD-only and PTSD-only groups consistently reported similar scores across all PTSD symptom scales. These findings further highlight the problematic diagnostic criteria and comorbidity in PTSD and emphasize the need to incorporate transdiagnostic treatment practices that focus on the overlapping symptoms, rather than specific diagnostic categories. Published by Elsevier Ltd. C1 [Gros, Daniel F.] Ralph H Johnson VAMC, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Gros, Daniel F.; Price, Matthew; Magruder, Kathryn M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU Veterans Affairs Health Services Research and Development (VA HSRD) [VCR-99-010-2]; [T32MH018869] FX This work was partially supported by grant VCR-99-010-2 from Veterans Affairs Health Services Research and Development (VA HSR&D) and several authors are members of the Ralph H. Johnson VAMC Research Enhancement Award Program (REA08-261; PI: Leonard Egede, M.D.). Dr. Price is supported by T32MH018869. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. There are no conflicts of interest to disclose. NR 36 TC 40 Z9 40 U1 3 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 30 PY 2012 VL 196 IS 2-3 BP 267 EP 270 DI 10.1016/j.psychres.2011.10.022 PG 4 WC Psychiatry SC Psychiatry GA 962MG UT WOS:000305548600017 PM 22386220 ER PT J AU He, C Rong, R Liu, J Wan, JB Zhou, KY Kang, JX AF He, Chengwei Rong, Rong Liu, Jing Wan, Jianbo Zhou, Keyuan Kang, Jing X. TI Effects of Coptis extract combined with chemotherapeutic agents on ROS production, multidrug resistance, and cell growth in A549 human lung cancer cells SO CHINESE MEDICINE LA English DT Article ID PLANT ANTITUMOR AGENTS; BERBERINE; APOPTOSIS; PROLIFERATION; CARCINOMA; DRUG; RHODAMINE-123; COMBINATION; INDUCTION; PATHWAY AB Background: Non-small cell lung cancer is associated with high expression of multidrug resistance (MDR) proteins and low production of reactive oxygen species (ROS). Coptis extract (COP), a Chinese medicinal herb, and its major constituent, berberine (BER), have anticancer properties. This study aims to investigate the effects of COP and BER combined with chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX), on cell proliferation, ROS production, and MDR in A549 human non-small cell lung cancer cells. Methods: A549 cells were treated with different doses of COP and BER, combined with 5-FU, CPT, and TAX. Cell viability was measured by an XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2 H-tetrazolium-5-carboxanilide) assay. Intracellular ROS levels were determined by measuring the oxidative conversion of cell permeable 2', 7'-dichlorofluorescein diacetate to fluorescent dichlorofluorescein. MDR of A549 cells was assessed by rhodamine 123 retention assay. Results: Both COP and BER significantly inhibited A549 cell growth in a dose-dependent manner. Combinations of COP or BER with chemotherapeutic agents (5-FU, CPT, and TAX) exhibited a stronger inhibitory effect on A549 cell growth. In addition, COP and BER increased ROS production and reduced MDR in A549 cells. Conclusion: As potential adjuvants to chemotherapy for non-small cell lung cancer, COP and BER increase ROS production, reduce MDR, and enhance the inhibitory effects of chemotherapeutic agents on A549 cell growth. C1 [He, Chengwei; Rong, Rong; Liu, Jing; Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA. [He, Chengwei; Rong, Rong; Liu, Jing; Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [He, Chengwei; Wan, Jianbo] Univ Macau, State Key Lab Qual Res Chinese Med, Macao, Sar, Peoples R China. [He, Chengwei; Wan, Jianbo] Univ Macau, Inst Chinese Med Sci, Macao, Sar, Peoples R China. [Rong, Rong] Sun Yat Sen Univ, Dept Nephrol, Affiliated Hosp 1, Guangzhou 510275, Guangdong, Peoples R China. [Zhou, Keyuan] Guangdong Med Coll, Biochem & Mol Biol Inst, Zhanjiang, Guangdong, Peoples R China. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA. EM kang.jing@mgh.harvard.edu RI Wan, Jian-Bo/D-8368-2014 OI Wan, Jian-Bo/0000-0002-6750-2617 FU NIH [CA113605]; National Natural Science Foundation of China [30672741] FX We thank Sarah A. Brigandi, Marilla C. Pender-Cudlip, and Erin D. Gleason for assistance in manuscript preparation. This work was partially supported by the NIH grant CA113605 (to JK) and the National Natural Science Foundation of China (30672741 to KZ). We also thank Dr. Qingwen Zhang from the University of Macau for providing Coptis extract. NR 30 TC 9 Z9 9 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-8546 J9 CHIN MED-UK JI Chin. Med. PD APR 30 PY 2012 VL 7 AR UNSP 11 DI 10.1186/1749-8546-7-11 PG 6 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA 165CQ UT WOS:000320460900002 PM 22546215 ER PT J AU Chan, AT Cook, NR AF Chan, Andrew T. Cook, Nancy R. TI Are we ready to recommend aspirin for cancer prevention? SO LANCET LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; COLORECTAL-CANCER; FOLLOW-UP; CHEMOPREVENTION; MORTALITY; HEALTH; RISK C1 [Cook, Nancy R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02215 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Cook, NR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. EM ncook@rics.bwh.harvard.edu FU NCI NIH HHS [R01 CA137178, R01 CA047988] NR 16 TC 17 Z9 17 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR 28 PY 2012 VL 379 IS 9826 BP 1569 EP 1571 DI 10.1016/S0140-6736(11)61654-1 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 934OB UT WOS:000303452600007 PM 22440945 ER PT J AU Grimsby, JL Porneala, BC Vassy, JL Yang, QH Florez, JC Dupuis, J Liu, TB Yesupriya, A Chang, MH Ned, RM Dowling, NF Khoury, MJ Meigs, JB AF Grimsby, Jonna L. Porneala, Bianca C. Vassy, Jason L. Yang, Quanhe Florez, Jose C. Dupuis, Josee Liu, Tiebin Yesupriya, Ajay Chang, Man-Huei Ned, Renee M. Dowling, Nicole F. Khoury, Muin J. Meigs, James B. CA MAGIC Investigators TI Race-ethnic differences in the association of genetic loci with HbA(1c) levels and mortality in US adults: the third National Health and Nutrition Examination Survey (NHANES III) SO BMC MEDICAL GENETICS LA English DT Article ID IRON-DEFICIENCY ANEMIA; HISPANIC WHITE ADULTS; HEMOGLOBIN A(1C); CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; HUMAN GENOME; GLYCATED HEMOGLOBIN; RACIAL-DIFFERENCES; PLASMA-GLUCOSE; A1C LEVELS AB Background: Hemoglobin A(1c) (HbA(1c)) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA(1c)-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA(1c) and 3) association of SNPs with mortality. Methods: We studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey) III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American) to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05. Results: RAFs varied widely and at six loci race-ethnic differences in RAF were significant (p < 0.0002), with NHB usually the most divergent. For instance, at ATP11A, the SNP RAF was 54% in NHB, 18% in MA and 14% in NHW (p < .0001). The mean genotype score differed by race-ethnicity (NHW: 10.4, NHB: 11.0, MA: 10.7, p < .0001), and was associated with increase in HbA(1c) in NHW (beta = 0.012 HbA(1c) increase per risk allele, p = 0.04) and MA (beta = 0.021, p = 0.005) but not NHB (beta = 0.007, p = 0.39). The genotype score was not associated with mortality in any group (NHW: OR (per risk allele increase in mortality) = 1.07, p = 0.09; NHB: OR = 1.04, p = 0.39; MA: OR = 1.03, p = 0.71). Conclusion: At many HbA(1c) loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA(1c)-associated variants on HbA(1c) levels varied by race-ethnicity, but did not influence mortality. C1 [Grimsby, Jonna L.; Porneala, Bianca C.; Vassy, Jason L.; Florez, Jose C.; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Grimsby, Jonna L.; Vassy, Jason L.; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Yang, Quanhe; Yesupriya, Ajay; Chang, Man-Huei; Ned, Renee M.; Dowling, Nicole F.; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM jmeigs@partners.org OI Dupuis, Josee/0000-0003-2871-3603 FU American Diabetes Association Mentored Post-Doctoral Fellowship Award; National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK078616]; NIDDK [K24 DK080140]; NIDDK Research Career Award [K23 DK65978]; Massachusetts General Hospital Physician Scientist Development Award; Doris Duke Charitable Foundation Clinical Scientist Development Award FX The data are from the NHANES III Public Use and Genetic Data Sets (http://www.cdc.gov/nchs/nhanes/genetics/genetic.htm). Supported by an American Diabetes Association Mentored Post-Doctoral Fellowship Award (Dr. Grimsby), National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK078616 (Dr Meigs), NIDDK K24 DK080140 (Dr Meigs), NIDDK Research Career Award K23 DK65978 (Dr Florez), a Massachusetts General Hospital Physician Scientist Development Award, and a Doris Duke Charitable Foundation Clinical Scientist Development Award (Dr Florez). The MAGIC Investigators are listed in the on-line supplement. We thank Sekar Kathiresan MD, for assistance in obtaining the NHANES III DNA that we used for genotyping, and Peter Shrader MS for analytic assistance. NR 56 TC 17 Z9 18 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD APR 27 PY 2012 VL 13 AR 30 DI 10.1186/1471-2350-13-30 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 000GA UT WOS:000308373300001 PM 22540250 ER PT J AU Shinagare, AB Zukotynski, KA Krajewski, KM Jagannathan, JP Butrynski, J Hornick, JL Ramaiya, NH AF Shinagare, A. B. Zukotynski, K. A. Krajewski, K. M. Jagannathan, J. P. Butrynski, J. Hornick, J. L. Ramaiya, N. H. TI Esophageal gastrointestinal stromal tumor: report of 7 patients SO CANCER IMAGING LA English DT Article DE Gastrointestinal stromal tumor; esophageal; CT; FDG-PET/CT ID IMATINIB MESYLATE; PHASE-II; GIST; FEATURES; KIT; CT AB Purpose: To evaluate imaging features of esophageal gastrointestinal stromal tumors (GIST) with clinical and histopathologic correlation and imaging follow-up. Materials and methods: In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, 14 patients with pathologically proven esophageal GIST seen from January 2001 to October 2011, 7 patients (4 women; mean age 70 years, range 56-87 years) who had imaging of primary tumor and follow-up imaging at our institution were included. Imaging studies were evaluated by 3 radiologists in consensus. Location, size and imaging features of primary tumor and metastases, if any, were recorded, and correlated with pathologic (histopathologic subtype, presence of necrosis, mitotic rate, immunohistochemical profile) and clinical (treatment-related changes, distant spread and outcome) parameters. Results: Of 7 tumors, 5 were located in the lower esophagus and 2 in mid-esophagus. Four were intraluminal, 2 were exophytic, and 1 was intramural. All 7 patients underwent computed tomography (CT); tumors appeared as well-circumscribed, hypoattenuating masses showing mild enhancement, with mean size of 5.7 x 4.2 cm. Necrosis and calcification were seen in 1 tumor each. Five patients underwent fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. GISTs were FDG avid with mean standardized uptake value (SUV)(max) of 9.5 (4.5-12.3). All tumors were positive for KIT (7/7) and CD34 (6/6). Distant metastases to liver and pleura were seen in 1 patient. On imatinib treatment, the tumors responded with decreased attenuation values and unchanged size on CT, and decreased SUVmax of primary tumor and metastases on FDG-PET/CT. Conclusion: Esophageal GISTs are well-circumscribed, FDG-avid, hypoattenuating masses that can metastasize to liver and pleura, and respond to imatinib treatment with decreased attenuation value on CT and decreased SUVmax on FDG-PET/CT. C1 [Shinagare, A. B.; Zukotynski, K. A.; Krajewski, K. M.; Jagannathan, J. P.; Ramaiya, N. H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Shinagare, A. B.; Zukotynski, K. A.; Krajewski, K. M.; Jagannathan, J. P.; Ramaiya, N. H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Butrynski, J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Butrynski, J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hornick, J. L.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM ashinagare@partners.org NR 22 TC 9 Z9 9 U1 0 U2 4 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 J9 CANCER IMAGING JI Cancer Imaging PD APR 27 PY 2012 VL 12 IS 1 BP 100 EP 108 DI 10.1102/1470-7330.2012.0017 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 961ZO UT WOS:000305508800001 PM 22542728 ER PT J AU Howard, S Jagannathan, J Krajewski, K Giardino, A Zukotynski, K Regan, KO Ghobrial, I Ramaiya, N AF Howard, Stephanie Jagannathan, Jyothi Krajewski, Katherine Giardino, Angela Zukotynski, Katherine Regan, Kevin O. Ghobrial, Irene Ramaiya, Nikhil TI Multimodality imaging in amyloidosis SO CANCER IMAGING LA English DT Review DE Amyloid; amyloidosis; multiple myeloma ID CT; SPECTRUM AB Amyloidosis comprises a rare spectrum of protein deposition diseases that diffusely or focally affect any organ. Amyloid's variable clinical presentation and nonspecific disease course often cause it to evade early diagnosis. This pictorial essay aims to familiarize radiologists with the pathophysiology of amyloidosis, to describe the basic classifications of amyloidosis, and to use multimodality imaging to illustrate its varied appearance throughout the body. This review highlights the diagnostic challenge of interpreting radiographic studies in patients with hematologic malignancies and concurrent amyloidosis. Radiologists should consider amyloid in chronically ill patients or patients with hematologic malignancies who have unusual/unexpected imaging findings. C1 [Howard, Stephanie; Jagannathan, Jyothi; Krajewski, Katherine; Giardino, Angela; Zukotynski, Katherine; Ghobrial, Irene; Ramaiya, Nikhil] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Regan, Kevin O.] Univ Cork, Dept Radiol, Cork, Ireland. RP Howard, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Imaging Radiol, 450 Brookline Ave, Boston, MA 02114 USA. EM sahoward@partners.org NR 15 TC 4 Z9 4 U1 0 U2 0 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 J9 CANCER IMAGING JI Cancer Imaging PD APR 27 PY 2012 VL 12 IS 1 BP 109 EP 117 DI 10.1102/1470-7330.2012.0023 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 961ZO UT WOS:000305508800002 PM 22542865 ER PT J AU Dewhirst, FE Klein, EA Thompson, EC Blanton, JM Chen, T Milella, L Buckley, CMF Davis, IJ Bennett, ML Marshall-Jones, ZV AF Dewhirst, Floyd E. Klein, Erin A. Thompson, Emily C. Blanton, Jessica M. Chen, Tsute Milella, Lisa Buckley, Catherine M. F. Davis, Ian J. Bennett, Marie-Lousie Marshall-Jones, Zoe V. TI The Canine Oral Microbiome SO PLOS ONE LA English DT Article ID 16S RIBOSOMAL-RNA; SP-NOV.; GEN. NOV.; BACTERIAL DIVERSITY; EMENDED DESCRIPTION; DOMAIN BACTERIA; PURE-CULTURE; FAM. NOV; PORPHYROMONAS; DOGS AB Determining the bacterial composition of the canine oral microbiome is of interest for two primary reasons. First, while the human oral microbiome has been well studied using molecular techniques, the oral microbiomes of other mammals have not been studied in equal depth using culture independent methods. This study allows a comparison of the number of bacterial taxa, based on 16S rRNA-gene sequence comparison, shared between humans and dogs, two divergent mammalian species. Second, canine oral bacteria are of interest to veterinary and human medical communities for understanding their roles in health and infectious diseases. The bacteria involved are mostly unnamed and not linked by 16S rRNA-gene sequence identity to a taxonomic scheme. This manuscript describes the analysis of 5,958 16S rRNA-gene sequences from 65 clone libraries. Full length 16S rRNA reference sequences have been obtained for 353 canine bacterial taxa, which were placed in 14 bacterial phyla, 23 classes, 37 orders, 66 families, and 148 genera. Eighty percent of the taxa are currently unnamed. The bacterial taxa identified in dogs are markedly different from those of humans with only 16.4% of oral taxa are shared between dogs and humans based on a 98.5% 16S rRNA sequence similarity cutoff. This indicates that there is a large divergence in the bacteria comprising the oral microbiomes of divergent mammalian species. The historic practice of identifying animal associated bacteria based on phenotypic similarities to human bacteria is generally invalid. This report describes the diversity of the canine oral microbiome and provides a provisional 16S rRNA based taxonomic scheme for naming and identifying unnamed canine bacterial taxa. C1 [Dewhirst, Floyd E.; Klein, Erin A.; Thompson, Emily C.; Blanton, Jessica M.; Chen, Tsute] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Milella, Lisa] Vet Dent Surg, Byfleet, Surrey, England. [Buckley, Catherine M. F.; Davis, Ian J.; Marshall-Jones, Zoe V.] WALTHAM Ctr Pet Nutr, Melton Mowbray, Leics, England. [Bennett, Marie-Lousie] Mars Pet Care Europe, Birstall, W Yorkshire, England. RP Dewhirst, FE (reprint author), Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. EM fdewhirst@forsyth.org FU WALTHAM Centre for Pet Nutrition FX This work was supported by the WALTHAM Centre for Pet Nutrition. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 47 Z9 47 U1 4 U2 28 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 27 PY 2012 VL 7 IS 4 AR e36067 DI 10.1371/journal.pone.0036067 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TJ UT WOS:000305336000117 PM 22558330 ER PT J AU Kelleher, RJ Geigenmuller, U Hovhannisyan, H Trautman, E Pinard, R Rathmell, B Carpenter, R Margulies, D AF Kelleher, Raymond J., III Geigenmueller, Ute Hovhannisyan, Hayk Trautman, Edwin Pinard, Robert Rathmell, Barbara Carpenter, Randall Margulies, David TI High-Throughput Sequencing of mGluR Signaling Pathway Genes Reveals Enrichment of Rare Variants in Autism SO PLOS ONE LA English DT Article ID COPY-NUMBER VARIATION; ACTIVATED PROTEIN-KINASES; AMINO-ACID SUBSTITUTIONS; LONG-TERM DEPRESSION; FRAGILE-X-SYNDROME; SPECTRUM DISORDERS; DE-NOVO; MENTAL-RETARDATION; SYNAPTIC PLASTICITY; TUBEROUS-SCLEROSIS AB Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms. This analysis revealed significant enrichment of rare functional variants in the mGluR pathway in autism cases. Higher burdens of rare, potentially deleterious variants were identified in autism cases for three pathway genes previously implicated in syndromic autism spectrum disorder, TSC1, TSC2, and SHANK3, suggesting that genetic variation in these genes also contributes to risk for non-syndromic autism. In addition, our analysis identified HOMER1, which encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, as a novel autism-risk gene. Rare, potentially deleterious HOMER1 variants identified uniquely in the autism population affected functionally important protein regions or regulatory sequences and co-segregated closely with autism among children of affected families. We also identified rare ASD-associated coding variants predicted to have damaging effects on components of the Ras/MAPK cascade. Collectively, these findings suggest that altered signaling downstream of mGluRs contributes to the pathogenesis of non-syndromic autism. C1 [Kelleher, Raymond J., III] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kelleher, Raymond J., III] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kelleher, Raymond J., III] Harvard Univ, Sch Med, Program Neurosci, Boston, MA USA. [Geigenmueller, Ute; Hovhannisyan, Hayk; Trautman, Edwin; Pinard, Robert; Margulies, David] Correlagen Diagnost Inc, Waltham, MA USA. [Rathmell, Barbara; Carpenter, Randall] Seaside Therapeut, Cambridge, MA USA. RP Kelleher, RJ (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM kelleher@helix.mgh.harvard.edu FU Pew Scholars Program in Biomedical Sciences; John Merck Scholars Fund; NIMH [K02 MH087796]; Simons Foundation Autism Research Initiative FX RJK was supported by awards from the Pew Scholars Program in Biomedical Sciences, the John Merck Scholars Fund, the NIMH (K02 MH087796), and the Simons Foundation Autism Research Initiative. These funding institutions had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Seaside Therapeutics and Correlagen Diagnostics contributed funding for this study. These companies had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript due to their employment of one or more of the authors of the study. NR 53 TC 38 Z9 38 U1 0 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 27 PY 2012 VL 7 IS 4 AR e35003 DI 10.1371/journal.pone.0035003 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TJ UT WOS:000305336000020 PM 22558107 ER PT J AU Plotkin, SR Bredella, MA Cai, WL Kassarjian, A Harris, GJ Esparza, S Merker, VL Munn, LL Muzikansky, A Askenazi, M Nguyen, R Wenzel, R Mautner, VF AF Plotkin, Scott R. Bredella, Miriam A. Cai, Wenli Kassarjian, Ara Harris, Gordon J. Esparza, Sonia Merker, Vanessa L. Munn, Lance L. Muzikansky, Alona Askenazi, Manor Rosa Nguyen Wenzel, Ralph Mautner, Victor F. TI Quantitative Assessment of Whole-Body Tumor Burden in Adult Patients with Neurofibromatosis SO PLOS ONE LA English DT Article ID DIAGNOSTIC-CRITERIA; TYPE-1; NF1; GENE; SCHWANNOMATOSIS; PHENOTYPE; MUTATION; MANIFESTATIONS; POPULATION; MORTALITY AB Purpose: Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis are at risk for multiple nerve sheath tumors and premature mortality. Traditional magnetic resonance imaging (MRI) has limited ability to assess disease burden accurately. The aim of this study was to establish an international cohort of patients with quantified whole-body internal tumor burden and to correlate tumor burden with clinical features of disease. Methods: We determined the number, volume, and distribution of internal nerve sheath tumors in patients using whole-body MRI (WBMRI) and three-dimensional computerized volumetry. We quantified the distribution of tumor volume across body regions and used unsupervised cluster analysis to group patients based on tumor distribution. We correlated the presence and volume of internal tumors with disease-related and demographic factors. Results: WBMRI identified 1286 tumors in 145/247 patients (59%). Schwannomatosis patients had the highest prevalence of tumors (P = 0.03), but NF1 patients had the highest median tumor volume (P = 0.02). Tumor volume was unevenly distributed across body regions with overrepresentation of the head/neck and pelvis. Risk factors for internal nerve sheath tumors included decreasing numbers of cafe-au-lait macules in NF1 patients (P = 0.003) and history of skeletal abnormalities in NF2 patients (P = 0.09). Risk factors for higher tumor volume included female gender (P = 0.05) and increasing subcutaneous neurofibromas (P = 0.03) in NF1 patients, absence of cutaneous schwannomas in NF2 patients (P = 0.06), and increasing age in schwannomatosis patients (p = 0.10). Conclusion: WBMRI provides a comprehensive phenotype of neurofibromatosis patients, identifies distinct anatomic subgroups, and provides the basis for investigating molecular biomarkers that correlate with unique disease manifestations. C1 [Plotkin, Scott R.; Esparza, Sonia; Merker, Vanessa L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.; Esparza, Sonia; Merker, Vanessa L.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Bredella, Miriam A.; Cai, Wenli; Harris, Gordon J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kassarjian, Ara] Corades SL, Dept Radiol, Majadahonda, Spain. [Munn, Lance L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Askenazi, Manor] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, Jerusalem, Israel. [Rosa Nguyen] Univ Hamburg Hosp, Dept Neurol, D-2000 Hamburg, Germany. [Wenzel, Ralph; Mautner, Victor F.] Univ Hamburg Hosp, Dept Radiol, D-2000 Hamburg, Germany. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM splotkin@partners.org RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Merker, Vanessa/0000-0002-4542-5227 FU Department of Defense [NF0502020]; United States National Institutes of Health/National Institute of Neurologic Disorders and Stroke [P01NS024279] FX This work was supported by grants from the Department of Defense Neurofibromatosis Research Program (NF0502020) and the United States National Institutes of Health/National Institute of Neurologic Disorders and Stroke (P01NS024279). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 25 Z9 25 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 27 PY 2012 VL 7 IS 4 AR e35711 DI 10.1371/journal.pone.0035711 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TJ UT WOS:000305336000051 PM 22558206 ER PT J AU Ying, HQ Kimmelman, AC Lyssiotis, CA Hua, SJ Chu, GC Fletcher-Sananikone, E Locasale, JW Son, J Zhang, HL Coloff, JL Yan, HY Wang, W Chen, SJ Viale, A Zheng, HW Paik, JH Lim, C Guimaraes, AR Martin, ES Chang, J Hezel, AF Perry, SR Hu, J Gan, BY Xiao, YH Asara, JM Weissleder, R Wang, YA Chin, L Cantley, LC DePinho, RA AF Ying, Haoqiang Kimmelman, Alec C. Lyssiotis, Costas A. Hua, Sujun Chu, Gerald C. Fletcher-Sananikone, Eliot Locasale, Jason W. Son, Jaekyoung Zhang, Hailei Coloff, Jonathan L. Yan, Haiyan Wang, Wei Chen, Shujuan Viale, Andrea Zheng, Hongwu Paik, Ji-hye Lim, Carol Guimaraes, Alexander R. Martin, Eric S. Chang, Jeffery Hezel, Aram F. Perry, Samuel R. Hu, Jian Gan, Boyi Xiao, Yonghong Asara, John M. Weissleder, Ralph Wang, Y. Alan Chin, Lynda Cantley, Lewis C. DePinho, Ronald A. TI Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose Metabolism SO CELL LA English DT Article ID N-LINKED CARBOHYDRATE; K-RAS ADDICTION; DUCTAL ADENOCARCINOMA; SUPPRESSOR GENES; CELL-GROWTH; CANCER; INDUCTION; MYC; EXPRESSION; BIOLOGY AB Tumor maintenance relies on continued activity of driver oncogenes, although their rate-limiting role is highly context dependent. Oncogenic Kras mutation is the signature event in pancreatic ductal adenocarcinoma (PDAC), serving a critical role in tumor initiation. Here, an inducible Kras(G12D)-driven PDAC mouse model establishes that advanced PDAC remains strictly dependent on Kras(G12D) expression. Transcriptome and metabolomic analyses indicate that Kras(G12D) serves a vital role in controlling tumor metabolism through stimulation of glucose uptake and channeling of glucose intermediates into the hexosamine biosynthesis and pentose phosphate pathways (PPP). These studies also reveal that oncogenic Kras promotes ribose biogenesis. Unlike canonical models, we demonstrate that Kras(G12D) drives glycolysis intermediates into the nonoxidative PPP, thereby decoupling ribose biogenesis from NADP/NADPH-mediated redox control. Together, this work provides in vivo mechanistic insights into how oncogenic Kras promotes metabolic reprogramming in native tumors and illuminates potential metabolic targets that can be exploited for therapeutic benefit in PDAC. C1 [Kimmelman, Alec C.; Son, Jaekyoung] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02215 USA. [Ying, Haoqiang; Hua, Sujun; Chu, Gerald C.; Fletcher-Sananikone, Eliot; Zhang, Hailei; Yan, Haiyan; Wang, Wei; Chen, Shujuan; Viale, Andrea; Zheng, Hongwu; Paik, Ji-hye; Lim, Carol; Martin, Eric S.; Chang, Jeffery; Hezel, Aram F.; Perry, Samuel R.; Hu, Jian; Gan, Boyi; Xiao, Yonghong; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Ying, Haoqiang; Hua, Sujun; Chu, Gerald C.; Fletcher-Sananikone, Eliot; Yan, Haiyan; Wang, Wei; Viale, Andrea; Zheng, Hongwu; Paik, Ji-hye; Lim, Carol; Martin, Eric S.; Chang, Jeffery; Hezel, Aram F.; Perry, Samuel R.; Hu, Jian; Gan, Boyi; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Lyssiotis, Costas A.; Locasale, Jason W.; Weissleder, Ralph; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Coloff, Jonathan L.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Asara, John M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Lyssiotis, Costas A.; Locasale, Jason W.; Asara, John M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. [Chu, Gerald C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wang, Wei] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Chin, Lynda] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Guimaraes, Alexander R.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Med Genet, Houston, TX 77030 USA. [DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. RP Kimmelman, AC (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02215 USA. EM alec_kimmelman@dfci.harvard.edu; rdepinho@mdanderson.org RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Zheng, Hongwu/0000-0002-5823-4913; Locasale, Jason/0000-0002-7766-3502 FU NIH [T32 CA009382-26, P01 CA117969]; BIDMC; National Cancer Institute [R01 CA157490]; Kimmel Scholar Award; AACR; Damon Runyon Fellowship FX We thank Christopher Wright for the p48-Cre mice; Shan Zhou and Shan Jiang for expert monitoring of the mouse colony; Yingchun Liu, Yuxiang Zheng, Ning Wu, Alexandra Grassian, Joan Brugge, Min Yuan, and Susanne Breitkopf for helpful suggestions and technical support. Grant support derives from NIH grants T32 CA009382-26 (H.Y.) and P01 CA117969 (R. W., L. C., L. C. C., R. A. D.). Imaging was supported by U24 CA092782 and P50 CA86355 (R. W.). Mass spectrometry was supported by 5P01CA120964-05 (L. C. C. and J.A.), 5P30CA006516-46 (J.A.), and the BIDMC Research Capital Fund. A. C. K. is supported by the National Cancer Institute Grant R01 CA157490, Kimmel Scholar Award and AACR-PanCAN Career Development Award. C. A. L. is the Amgen Fellow of the Damon Runyon Cancer Research Foundation (DRG-2056-10). S. H. is supported by a Damon Runyon Fellowship. A. C. K. is a Consultant for Forma Therapeutics. L. C. C. is a founder of Agios Pharmaceuticals, a company developing drugs to target metabolic enzymes for cancer therapy. NR 52 TC 389 Z9 396 U1 16 U2 111 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 27 PY 2012 VL 149 IS 3 BP 656 EP 670 DI 10.1016/j.cell.2012.01.058 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 934KN UT WOS:000303443100016 PM 22541435 ER PT J AU Talkowski, ME Rosenfeld, JA Blumenthal, I Pillalamarri, V Chiang, C Heilbut, A Ernst, C Hanscom, C Rossin, E Lindgren, AM Pereira, S Ruderfer, D Kirby, A Ripke, S Harris, DJ Lee, JH Ha, K Kim, HG Solomon, BD Gropman, AL Lucente, D Sims, K Ohsumi, TK Borowsky, ML Loranger, S Quade, B Lage, K Miles, J Wu, BL Shen, YP Neale, B Shaffer, LG Daly, MJ Morton, CC Gusella, JF AF Talkowski, Michael E. Rosenfeld, Jill A. Blumenthal, Ian Pillalamarri, Vamsee Chiang, Colby Heilbut, Adrian Ernst, Carl Hanscom, Carrie Rossin, Elizabeth Lindgren, Amelia M. Pereira, Shahrin Ruderfer, Douglas Kirby, Andrew Ripke, Stephan Harris, David J. Lee, Ji-Hyun Ha, Kyungsoo Kim, Hyung-Goo Solomon, Benjamin D. Gropman, Andrea L. Lucente, Diane Sims, Katherine Ohsumi, Toshiro K. Borowsky, Mark L. Loranger, Stephanie Quade, Bradley Lage, Kasper Miles, Judith Wu, Bai-Lin Shen, Yiping Neale, Benjamin Shaffer, Lisa G. Daly, Mark J. Morton, Cynthia C. Gusella, James F. TI Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries SO CELL LA English DT Article ID AUTISM SPECTRUM DISORDERS; PITT-HOPKINS-SYNDROME; CHROMATIN REMODELING FACTOR; GENOME-WIDE ASSOCIATION; MICRODELETION SYNDROME; DEVELOPMENTAL DELAY; SUSCEPTIBILITY LOCI; BIPOLAR DISORDER; CHD8 INTERACTS; SCHIZOPHRENIA AB Balanced chromosomal abnormalities (BCAs) represent a relatively untapped reservoir of single-gene disruptions in neurodevelopmental disorders (NDDs). We sequenced BCAs in patients with autism or related NDDs, revealing disruption of 33 loci in four general categories: (1) genes previously associated with abnormal neurodevelopment (e. g., AUTS2, FOXP1, and CDKL5), (2) single-gene contributors to microdeletion syndromes (MBD5, SATB2, EHMT1, and SNURF-SNRPN), (3) novel risk loci (e. g., CHD8, KIRREL3, and ZNF507), and (4) genes associated with later-onset psychiatric disorders (e. g., TCF4, ZNF804A, PDE10A, GRIN2B, and ANK3). We also discovered among neurodevelopmental cases a profoundly increased burden of copy-number variants from these 33 loci and a significant enrichment of polygenic risk alleles from genome-wide association studies of autism and schizophrenia. Our findings suggest a polygenic risk model of autism and reveal that some neurodevelopmental genes are sensitive to perturbation by multiple mutational mechanisms, leading to variable phenotypic outcomes that manifest at different life stages. C1 [Talkowski, Michael E.; Blumenthal, Ian; Pillalamarri, Vamsee; Chiang, Colby; Heilbut, Adrian; Ernst, Carl; Hanscom, Carrie; Rossin, Elizabeth; Ruderfer, Douglas; Kirby, Andrew; Ripke, Stephan; Lee, Ji-Hyun; Lucente, Diane; Sims, Katherine; Shen, Yiping; Neale, Benjamin; Daly, Mark J.; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Rossin, Elizabeth; Kirby, Andrew; Ripke, Stephan; Lage, Kasper; Neale, Benjamin; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ohsumi, Toshiro K.; Borowsky, Mark L.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Quade, Bradley; Wu, Bai-Lin; Shen, Yiping; Morton, Cynthia C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Talkowski, Michael E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Talkowski, Michael E.; Rossin, Elizabeth; Ruderfer, Douglas; Kirby, Andrew; Ripke, Stephan; Lage, Kasper; Neale, Benjamin; Daly, Mark J.; Morton, Cynthia C.; Gusella, James F.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02143 USA. [Rosenfeld, Jill A.; Shaffer, Lisa G.] PerkinElmer Inc, Signature Genom Labs, Spokane, WA 99207 USA. [Lindgren, Amelia M.; Pereira, Shahrin; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet, Boston, MA 02115 USA. [Lindgren, Amelia M.; Pereira, Shahrin; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Gynecol, Boston, MA 02115 USA. [Lindgren, Amelia M.; Pereira, Shahrin; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Reprod Biol, Boston, MA 02115 USA. [Harris, David J.] Childrens Hosp Boston, Div Clin Genet, Boston, MA 02115 USA. [Wu, Bai-Lin; Shen, Yiping] Childrens Hosp Boston, Dept Lab Med, Boston, MA 02115 USA. [Ha, Kyungsoo] Georgia Hlth Sci Univ, Canc Res Ctr, Augusta, GA 30912 USA. [Kim, Hyung-Goo] Georgia Hlth Sci Univ, Inst Mol Med & Genet, Dept Obstet & Gynecol, Augusta, GA 30912 USA. [Solomon, Benjamin D.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Gropman, Andrea L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Gropman, Andrea L.] George Washington Univ Hlth Sci, Dept Neurol, Washington, DC 20052 USA. [Loranger, Stephanie; Daly, Mark J.; Gusella, James F.] Autism Consortium Boston, Boston, MA 02115 USA. [Lage, Kasper] Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Surg Res Labs, Boston, MA 02114 USA. [Lage, Kasper] Tech Univ Denmark, Ctr Biol Sequence Anal, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Lage, Kasper] Univ Copenhagen, Ctr Prot Res, DK-1165 Copenhagen, Denmark. [Miles, Judith] Univ Missouri Hosp & Clin, Thompson Ctr Autism & Neurodev Disorders, Dept Pediat, Columbia, MO 65201 USA. [Miles, Judith] Univ Missouri Hosp & Clin, Thompson Ctr Autism & Neurodev Disorders, Dept Med Genet, Columbia, MO 65201 USA. [Miles, Judith] Univ Missouri Hosp & Clin, Thompson Ctr Autism & Neurodev Disorders, Dept Pathol, Columbia, MO 65201 USA. [Wu, Bai-Lin] Fudan Univ, Childrens Hosp, Shanghai 200032, Peoples R China. [Wu, Bai-Lin] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China. [Shen, Yiping] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Shanghai 200025, Peoples R China. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu RI Heilbut, Adrian/J-9427-2012; Ruderfer, Douglas/M-5795-2016; OI Heilbut, Adrian/0000-0002-8169-7967; Ruderfer, Douglas/0000-0002-2365-386X; Chiang, Colby/0000-0002-4113-6065 FU National Institutes of Health [GM061354, HD065286]; Simons Foundation Autism Research Initiative; Autism Speaks; Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health and Human Services; National Institute of Mental Health National Research Service [MH087123]; Massachusetts General Hospital Executive Committee FX We are grateful to all participating subjects and families and to the many healthcare professionals who have contributed to this study, including Mary-Alice Abbott, Darius J. Adams, Kwame Anyane-Yeboa, Stephen G. Bamforth, Tina Bartell, David P. Bick, Joann N. Bodurtha, Carol Clericuzio, Stephanie Cohen, Kristin Dalton, Maria Descartes, Joanne Milisa Drautz, Dawn L. Earl, Luis F. Escobar, Shannon Gerner, Edwin Guzman, Kenneth Handelman, Tim Heshka, Robert J. Hopkin, Micheil Innes, Debby Lambert, Emmanuelle Lemyre, Cynthia Lim, Livija Medne, Graciela Moya, Katie Rutledge, Wendy Smith, Mark Stephan, Darci Sternen, Katie Stoll, Paulien van Galen, Nancy J. Van Vranken, Erica Wahl, Susan E. Wiley, Amy L. White, Anne Woods, and Elaine H. Zackai. The invaluable control data for this study were provided by Pamela Sklar, Shaun Purcell, the International Schizophrenia Consortium, the Wellcome Trust Case Control Consortium, Evan Eichler, Bradley Coe, and Greg Cooper. We thank Tammy Gillis, Mary Anne Anderson, Jayla Ruliera, and Thon de Boer for technical assistance. We also thank Dennis Gurgul, Nilay Roy, and Brent Richter of Partners Research Computing at Massachusetts General Hospital, and contributing staff from Signature Genomic Laboratories and Children's Hospital Boston. This work was funded by grants GM061354 and HD065286 from the National Institutes of Health, the Simons Foundation Autism Research Initiative, and Autism Speaks. This research was also supported by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health and Human Services. M. T. was supported by a National Institute of Mental Health National Research Service Award (MH087123) and an Massachusetts General Hospital Executive Committee on Research Fund for Medical Discovery Award. L. G. S. and J. A. R. are employees of Signature Genomic Laboratories, PerkinElmer. NR 45 TC 220 Z9 227 U1 3 U2 41 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 27 PY 2012 VL 149 IS 3 DI 10.1016/j.cell.2012.03.028 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 934KN UT WOS:000303443100006 PM 22521361 ER PT J AU Moslehi, J DePinho, RA Sahin, E AF Moslehi, Javid DePinho, Ronald A. Sahin, Erguen TI Telomeres and Mitochondria in the Aging Heart SO CIRCULATION RESEARCH LA English DT Review DE heart aging; telomere; mitochondria; metabolism; PGC-1 alpha; myocardial regeneration; telomerase; transcription factors; transcriptional coactivator ID CARDIOVASCULAR-DISEASE ENTERPRISES; TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; CAUSES CARDIAC DYSFUNCTION; HEMATOPOIETIC STEM-CELLS; REPEAT-CONTAINING RNA; OXIDATIVE STRESS; WERNER-SYNDROME; DYSKERATOSIS-CONGENITA; DILATED CARDIOMYOPATHY; MAJOR SHAREHOLDERS AB Studies in humans and in mice have highlighted the importance of short telomeres and impaired mitochondrial function in driving age-related functional decline in the heart. Although telomere and mitochondrial dysfunction have been viewed mainly in isolation, recent studies in telomerase-deficient mice have provided evidence for an intimate link between these two processes. Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1 alpha and PGC-1 beta in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging. (Circ Res. 2012;110:1226-1237.) C1 [Sahin, Erguen] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. [Sahin, Erguen] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. [DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Moslehi, Javid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Moslehi, Javid] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Cardiovasc Med, Boston, MA 02115 USA. RP Sahin, E (reprint author), Baylor Coll Med, Huffington Ctr Aging, 1 Baylor Plaza,MS230, Houston, TX 77030 USA. EM rdepinho@mdanderson.org; esahin@bcm.edu FU National Institutes of Health [K08HL097031]; Brigham and Women's Hospital; Deutsche Forschungsgemeinschaft; NIH National Cancer Institute [R01CA84628, 1U01CA141508-01]; Robert A. and Renee E. Belfer Foundation; Ellison Foundation; American Cancer Society FX J.M. is supported by a National Institutes of Health training grant for cardiovascular research (K08HL097031) and the Watkins Cardiovascular Discovery Award (from Brigham and Women's Hospital). E.S. was supported by the Deutsche Forschungsgemeinschaft, and R.A.D. is supported by R01CA84628 and 1U01CA141508-01 grants from the NIH National Cancer Institute and the Robert A. and Renee E. Belfer Foundation. R.A.D. was supported by an Ellison Foundation for Medical Research Senior Scholar and an American Cancer Society Research Professor Award. NR 121 TC 34 Z9 36 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 27 PY 2012 VL 110 IS 9 BP 1226 EP 1237 DI 10.1161/CIRCRESAHA.111.246868 PG 12 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 933ZI UT WOS:000303406200018 PM 22539756 ER PT J AU Bunting, SF Callen, E Kozak, ML Kim, JM Wong, N Lopez-Contreras, AJ Ludwig, T Baer, R Faryabi, RB Malhowski, A Chen, HT Fernandez-Capetillo, O D'Andrea, A Nussenzweig, A AF Bunting, Samuel F. Callen, Elsa Kozak, Marina L. Kim, Jung Min Wong, Nancy Lopez-Contreras, Andres J. Ludwig, Thomas Baer, Richard Faryabi, Robert B. Malhowski, Amy Chen, Hua-Tang Fernandez-Capetillo, Oscar D'Andrea, Alan Nussenzweig, Andre TI BRCA1 Functions Independently of Homologous Recombination in DNA Interstrand Crosslink Repair SO MOLECULAR CELL LA English DT Article ID STRAND-BREAK REPAIR; CLASS-SWITCH RECOMBINATION; FANCONI-ANEMIA PATHWAY; V(D)J RECOMBINATION; DAMAGE-RESPONSE; CELL-CYCLE; POLY(ADP-RIBOSE) POLYMERASE; TUMOR SUPPRESSION; DEFICIENT CELLS; 53BP1 AB Brca1 is required for DNA repair by homologous recombination (HR) and normal embryonic development. Here we report that deletion of the DNA damage response factor 53BP1 overcomes embryonic lethality in Brca1-nullizygous mice and rescues HR deficiency, as measured by hypersensitivity to polyADP-ribose polymerase (PARP) inhibition. However, Brca1,53BP1 double-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), indicating that BRCA1 has an additional role in DNA crosslink repair that is distinct from HR. Disruption of the nonhomologous end-joining (NHEJ) factor, Ku, promotes DNA repair in Brca1-deficient cells; however deletion of either Ku or 53BP1 exacerbates genomic instability in cells lacking FANCD2, a mediator of the Fanconi anemia pathway for ICL repair. BRCA1 therefore has two separate roles in ICL repair that can be modulated by manipulating NHEJ, whereas FANCD2 provides a key activity that cannot be bypassed by ablation of 53BP1 or Ku. C1 [Bunting, Samuel F.; Callen, Elsa; Kozak, Marina L.; Wong, Nancy; Faryabi, Robert B.; Malhowski, Amy; Chen, Hua-Tang; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA. [Ludwig, Thomas; Baer, Richard] Columbia Univ, Med Ctr, Irving Canc Res Ctr, Inst Canc Genet, New York, NY 10032 USA. [Kim, Jung Min; D'Andrea, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Lopez-Contreras, Andres J.; Fernandez-Capetillo, Oscar] Spanish Natl Canc Res Ctr, Genom Instabil Grp, Madrid, Spain. RP Nussenzweig, A (reprint author), NCI, Lab Genome Integr, NIH, 37 Convent Dr,Room 1108, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov RI Faryabi, Robert/H-3544-2015; Fernandez-Capetillo, Oscar/H-3508-2015; Ludwig, Thomas/Q-6484-2016; OI Faryabi, Robert/0000-0002-7931-2175; Fernandez-Capetillo, Oscar/0000-0002-2690-6885; Ludwig, Thomas/0000-0003-3461-2585; Lopez-Contreras, Andres Joaquin/0000-0002-5517-7327 FU NIH; National Cancer Institute; Center for Cancer Research; Department of Defense [BC102335, K99/R00, 1K99CA160574-01] FX We thank Laura Niedernhofer, Jeremy Daniel, and Elise Kohn for helpful discussions and suggestions; Mark O'Connor for Parpi; and Michael Eckhaus and Mark Bryant for assistance with histology. The work was supported by the Intramural Research Program of the NIH, the National Cancer Institute, and the Center for Cancer Research, and by a Department of Defense grant to A.N. (BC102335) and a K99/R00 grant (1K99CA160574-01) to S.B. Research was conducted in compliance with the Animal Welfare Act Regulations and other federal statutes relating to animals and experiments involving animals and adheres to the principles set forth in the Guide for Care and Use of Laboratory Animals, National Research Council, 1996. NR 56 TC 108 Z9 110 U1 3 U2 23 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 APR 27 PY 2012 VL 46 IS 2 BP 125 EP 135 DI 10.1016/j.molcel.2012.02.015 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 933MH UT WOS:000303365300004 PM 22445484 ER PT J AU Janas, MM Wang, E Love, T Harris, AS Stevenson, K Semmelmann, K Shaffer, JM Chen, PH Doench, JG Yerramilli, SVBK Neuberg, DS Iliopoulos, D Housman, DE Burge, CB Novina, CD AF Janas, Maja M. Wang, Eric Love, Tara Harris, Abigail S. Stevenson, Kristen Semmelmann, Karlheinz Shaffer, Jonathan M. Chen, Po-Hao Doench, John G. Yerramilli, Subrahmanyam V. B. K. Neuberg, Donna S. Iliopoulos, Dimitrios Housman, David E. Burge, Christopher B. Novina, Carl D. TI Reduced Expression of Ribosomal Proteins Relieves MicroRNA-Mediated Repression SO MOLECULAR CELL LA English DT Article ID DIAMOND-BLACKFAN ANEMIA; HUMAN-PAPILLOMAVIRUS TYPE-16; MESSENGER-RNA DEGRADATION; HUMAN-CELLS; TUMOR-SUPPRESSOR; C-ELEGANS; POSTTRANSCRIPTIONAL REGULATION; TRANSLATION INITIATION; CAENORHABDITIS-ELEGANS; LET-7 MICRORNA AB MicroRNAs (miRNAs) regulate physiological and pathological processes by inducing posttranscriptional repression of target messenger RNAs (mRNAs) via incompletely understood mechanisms. To discover factors required for human miRNA activity, we performed an RNAi screen using a reporter cell line of miRNA-mediated repression of translation initiation. We report that reduced expression of ribosomal protein genes (RPGs) dissociated miRNA complexes from target mRNAs, leading to increased polysome association, translation, and stability of miRNA-targeted mRNAs relative to untargeted mRNAs. RNA sequencing of polysomes indicated substantial overlap in sets of genes exhibiting increased or decreased polysomal association after Argonaute or RPG knockdowns, suggesting similarity in affected pathways. miRNA profiling of monosomes and polysomes demonstrated that miRNAs cosediment with ribosomes. RPG knockdowns decreased miRNAs in monosomes and increased their target mRNAs in polysomes. Our data show that most miRNAs repress translation and that the levels of RPGs modulate miRNA-mediated repression of translation initiation. C1 [Janas, Maja M.; Love, Tara; Chen, Po-Hao; Iliopoulos, Dimitrios; Novina, Carl D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Stevenson, Kristen; Neuberg, Donna S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Janas, Maja M.; Love, Tara; Chen, Po-Hao; Iliopoulos, Dimitrios; Novina, Carl D.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Janas, Maja M.; Love, Tara; Chen, Po-Hao; Doench, John G.; Novina, Carl D.] Broad Inst Harvard & MIT, Cambridge, MA 02141 USA. [Wang, Eric; Housman, David E.; Burge, Christopher B.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Wang, Eric; Housman, David E.] MIT, Robert Koch Inst, Cambridge, MA 02139 USA. [Harris, Abigail S.; Semmelmann, Karlheinz; Shaffer, Jonathan M.; Yerramilli, Subrahmanyam V. B. K.] Qiagen, Frederick, MD 21703 USA. RP Novina, CD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM carl_novina@dfci.harvard.edu OI Doench, John/0000-0002-3707-9889 FU W.M. Keck Foundation FX We would like to thank Dr. Steffen Schubert and The Institute of Chemistry and Cell Biology (ICCB) Screening Facility at Harvard Medical School for helping with designing and performing the RNAi screen. We also thank Dr. Stephen Buratowski, Dr. Danesh Moazed, Dr. Kai Wucherpfennig, and Dustin Griesemer for insightful discussions. This work was supported by a Distinguished Young Scholars Award from the W.M. Keck Foundation to C.D.N. NR 64 TC 16 Z9 16 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD APR 27 PY 2012 VL 46 IS 2 BP 171 EP 186 DI 10.1016/j.molcel.2012.04.008 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 933MH UT WOS:000303365300008 PM 22541556 ER PT J AU Jacquemont, C Simon, JA D'Andrea, AD Taniguchi, T AF Jacquemont, Celine Simon, Julian A. D'Andrea, Alan D. Taniguchi, Toshiyasu TI Non-specific chemical inhibition of the Fanconi anemia pathway sensitizes cancer cells to cisplatin SO MOLECULAR CANCER LA English DT Article DE Fanconi anemia; Drug resistance; Cisplatin; Small molecule; Homologous recombination ID DNA-DAMAGE RESPONSE; STRAND BREAK REPAIR; MAMMALIAN-CELLS; TUMOR-CELLS; FANCD2 MONOUBIQUITINATION; REPLICATION STRESS; CHK1 FUNCTION; RECOMBINATION; CHECKPOINT; PROTEIN AB Background: Platinum compounds such as cisplatin and carboplatin are DNA crosslinking agents widely used for cancer chemotherapy. However, the effectiveness of platinum compounds is often tempered by the acquisition of cellular drug resistance. Until now, no pharmacological approach has successfully overcome cisplatin resistance in cancer treatment. Since the Fanconi anemia (FA) pathway is a DNA damage response pathway required for cellular resistance to DNA interstrand crosslinking agents, identification of small molecules that inhibit the FA pathway may reveal classes of chemicals that sensitize cancer cells to cisplatin. Results: Through a cell-based screening assay of over 16,000 chemicals, we identified 26 small molecules that inhibit ionizing radiation and cisplatin-induced FANCD2 foci formation, a marker of FA pathway activity, in multiple human cell lines. Most of these small molecules also compromised ionizing radiation-induced RAD51 foci formation and homologous recombination repair, indicating that they are not selective toward the regulation of FANCD2. These compounds include known inhibitors of the proteasome, cathepsin B, lysosome, CHK1, HSP90, CDK and PKC, and several uncharacterized chemicals including a novel proteasome inhibitor (Chembridge compound 5929407). Isobologram analyses demonstrated that half of the identified molecules sensitized ovarian cancer cells to cisplatin. Among them, 9 demonstrated increased efficiency toward FA pathway-proficient, cisplatin-resistant ovarian cancer cells. Six small molecules, including bortezomib (proteasome inhibitor), CA-074-Me (cathepsin B inhibitor) and 17-AAG (HSP90 inhibitor), synergized with cisplatin specifically in FA-proficient ovarian cancer cells (2008 + FANCF), but not in FA-deficient isogenic cells (2008). In addition, geldanamycin (HSP90 inhibitor) and two CHK1 inhibitors (UCN-01 and SB218078) exhibited a significantly stronger synergism with cisplatin in FA-proficient cells when compared to FA-deficient cells, suggesting a contribution of their FA pathway inhibitory activity to cisplatin sensitization. Conclusion: Our findings suggest that, despite their lack of specificity, pharmaceutical inhibition of the FA pathway by bortezomib, CA-074-Me, CHK1 inhibitors or HSP90 inhibitors may be a promising strategy to sensitize cisplatin-resistant, FA pathway-proficient tumor cells to cisplatin. In addition, we identified four new small molecules which synergize with cisplatin. Further development of their analogs and evaluation of their combination with cisplatin may lead to the development of efficient cancer treatments. C1 [Jacquemont, Celine; Taniguchi, Toshiyasu] Howard Hughes Med Inst, Chevy Chase, MD USA. [Jacquemont, Celine; Simon, Julian A.; Taniguchi, Toshiyasu] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA. [Jacquemont, Celine; Taniguchi, Toshiyasu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Simon, Julian A.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Taniguchi, T (reprint author), Howard Hughes Med Inst, Chevy Chase, MD USA. EM ttaniguc@fhcrc.org FU NCI NIH HHS [R01 CA125636, P30 CA015704]; NHLBI NIH HHS [R37 HL052725]; NIDDK NIH HHS [R01 DK043889] NR 52 TC 24 Z9 26 U1 2 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD APR 26 PY 2012 VL 11 AR 26 DI 10.1186/1476-4598-11-26 PG 14 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 025VK UT WOS:000310223700001 PM 22537224 ER PT J AU Jensen, KB Loitoile, R Kosek, E Petzke, F Carville, S Fransson, P Marcus, H Williams, SCR Choy, E Mainguy, Y Vitton, O Gracely, RH Gollub, R Ingvar, M Kong, J AF Jensen, Karin B. Loitoile, Rita Kosek, Eva Petzke, Frank Carville, Serena Fransson, Peter Marcus, Hanke Williams, Steven C. R. Choy, Ernest Mainguy, Yves Vitton, Olivier Gracely, Richard H. Gollub, Randy Ingvar, Martin Kong, Jian TI Patients with fibromyalgia display less functional connectivity in the brain's pain inhibitory network SO MOLECULAR PAIN LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HUMAN ORBITOFRONTAL CORTEX; CEREBRAL BLOOD-FLOW; NEUROPATHIC PAIN; INDUCED EXPECTATIONS; PLACEBO ANALGESIA; MECHANISMS; PERCEPTION; MODULATION; ANXIETY AB Background: There is evidence for augmented processing of pain and impaired endogenous pain inhibition in Fibromyalgia syndrome (FM). In order to fully understand the mechanisms involved in FM pathology, there is a need for closer investigation of endogenous pain modulation. In the present study, we compared the functional connectivity of the descending pain inhibitory network in age-matched FM patients and healthy controls (HC). We performed functional magnetic resonance imaging (fMRI) in 42 subjects; 14 healthy and 28 age-matched FM patients (2 patients per HC), during randomly presented, subjectively calibrated pressure pain stimuli. A seed-based functional connectivity analysis of brain activity was performed. The seed coordinates were based on the findings from our previous study, comparing the fMRI signal during calibrated pressure pain in FM and HC: the rostral anterior cingulate cortex (rACC) and thalamus. Results: FM patients required significantly less pressure (kPa) to reach calibrated pain at 50 mm on a 0-100 visual analogue scale (p < .001, two-tailed). During fMRI scanning, the rACC displayed significantly higher connectivity to the amygdala, hippocampus, and brainstem in healthy controls, compared to FM patients. There were no regions where FM patients showed higher rACC connectivity. Thalamus showed significantly higher connectivity to the orbitofrontal cortex in healthy controls but no regions showed higher thalamic connectivity in FM patients. Conclusion: Patients with FM displayed less connectivity within the brain's pain inhibitory network during calibrated pressure pain, compared to healthy controls. The present study provides brain-imaging evidence on how brain regions involved in homeostatic control of pain are less connected in FM patients. It is possible that the dysfunction of the descending pain modulatory network plays an important role in maintenance of FM pain and our results may translate into clinical implications by using the functional connectivity of the pain modulatory network as an objective measure of pain dysregulation. C1 [Jensen, Karin B.; Loitoile, Rita; Gollub, Randy; Kong, Jian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Jensen, Karin B.; Loitoile, Rita; Gollub, Randy; Kong, Jian] Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Kosek, Eva; Fransson, Peter; Ingvar, Martin] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Kosek, Eva; Ingvar, Martin] Karolinska Inst, Osher Ctr Integrat Med, Stockholm, Sweden. [Petzke, Frank] Univ Med Ctr, Ctr Anesthesiol Emergency & Intens Care Med, Pain Clin, Gottingen, Germany. [Carville, Serena] UK Age Res Forum, London, England. [Marcus, Hanke] Univ Hosp Cologne, Dept Anesthesiol & Postoperat Intens Care Med, Cologne, Germany. [Williams, Steven C. R.] Kings Coll London, Inst Psychiat, Ctr Neuroimaging Sci, London WC2R 2LS, England. [Choy, Ernest] Cardiff Univ, Sch Med, Dept Med, Cardiff, Wales. [Mainguy, Yves; Vitton, Olivier] Pierre Fabre Medicament, Labege, France. [Gracely, Richard H.] Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC USA. RP Jensen, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM karinj@nmr.mgh.harvard.edu RI Williams, Steve/D-6979-2011; Fransson, Peter/M-5679-2014; OI Williams, Steve/0000-0003-4299-1941; Fransson, Peter/0000-0002-1305-9875; Gollub, Randy L./0000-0002-9434-4044; Ingvar, Martin/0000-0002-9041-5714; Jensen, Karin/0000-0003-2521-3160 FU Pierre Fabre [2004-004249-16]; Marie Curie Postdoc Program at the Swedish Council for Working Life and Social Research; NIH/NCCAM [KO1AT003883, R21AT004497, R01AT006364, R01AT005280]; NIH/NIDA [R03AT218317] FX This study was performed in collaboration with the pharmaceutical company Pierre Fabre. The results are in part derived from a placebo controlled drug intervention study (EudraCT # 2004-004249-16) financed by Pierre Fabre. KBJ received support from the Marie Curie Postdoc Program at the Swedish Council for Working Life and Social Research. Other support for the authors include KO1AT003883 (NIH/NCCAM), R21AT004497 (NIH/NCCAM), R03AT218317 (NIH/NIDA), R01AT006364 (NIH/NCCAM) to JK, R01AT005280 (NIH/NCCAM) to RG. NR 66 TC 72 Z9 73 U1 4 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD APR 26 PY 2012 VL 8 AR 32 DI 10.1186/1744-8069-8-32 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 986MT UT WOS:000307346400001 PM 22537768 ER PT J AU Attar, EC AF Attar, Eyal C. TI Get out-and stay out SO BLOOD LA English DT Editorial Material ID ACUTE MYELOGENOUS LEUKEMIA; CXCR4 ANTAGONIST AMD3100; PROGENITOR CELLS; NOD/SCID MICE; MOBILIZATION; AML C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Attar, EC (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 26 PY 2012 VL 119 IS 17 BP 3869 EP 3870 PG 2 WC Hematology SC Hematology GA 959AU UT WOS:000305282900001 PM 22538491 ER PT J AU Westerberg, LS Dahlberg, C Baptista, M Moran, CJ Detre, C Keszei, M Eston, MA Alt, FW Terhorst, C Notarangelo, LD Snapper, SB AF Westerberg, Lisa S. Dahlberg, Carin Baptista, Marisa Moran, Christopher J. Detre, Cynthia Keszei, Marton Eston, Michelle A. Alt, Frederick W. Terhorst, Cox Notarangelo, Luigi D. Snapper, Scott B. TI Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function SO BLOOD LA English DT Article ID MARGINAL ZONE; WHITE PULP; T-CELLS; DEFICIENCY; MICE; MACROPHAGES; ABNORMALITIES; AUTOIMMUNITY; ORGANIZATION; LYMPHOCYTES AB The Wiskott-Aldrich syndrome protein (WASP) is a key cytoskeletal regulator of hematopoietic cells. Although WASP-knockout (WKO) mice have aberrant B-cell cytoskeletal responses, B-cell development is relatively normal. We hypothesized that N-WASP, a ubiquitously expressed homolog of WASP, may serve some redundant functions with WASP in B cells. In the present study, we generated mice lacking WASP and N-WASP in B cells (conditional double knockout [cDKO] B cells) and show that cDKO mice had decreased numbers of follicular and marginal zone B cells in the spleen. Receptor-induced activation of cDKO B cells led to normal proliferation but a marked reduction of spreading compared with wild-type and WKO B cells. Whereas WKO B cells showed decreased migration in vitro and homing in vivo compared with wild-type cells, cDKO B cells showed an even more pronounced decrease in the migratory response in vivo. After injection of 2,4,6-trinitrophenol (TNP)-Ficoll, cDKO B cells had reduced antigen uptake in the splenic marginal zone. Despite high basal serum IgM, cDKO mice mounted a reduced immune response to the T cell-independent antigen TNP-Ficoll and to the T cell-dependent antigen TNP-keyhole limpet hemocyanin. Our results reveal that the combined activity of WASP and N-WASP is required for peripheral B-cell development and function. (Blood. 2012;119(17):3966-3974) C1 [Snapper, Scott B.] Harvard Univ, Sch Med, Div Gastroenterol, Childrens Hosp, Boston, MA 02115 USA. [Westerberg, Lisa S.; Dahlberg, Carin; Baptista, Marisa] Karolinska Inst, Dept Med, Translat Immunol Unit, S-17176 Stockholm, Sweden. [Westerberg, Lisa S.; Moran, Christopher J.; Eston, Michelle A.; Snapper, Scott B.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Westerberg, Lisa S.; Moran, Christopher J.; Eston, Michelle A.; Snapper, Scott B.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Westerberg, Lisa S.; Moran, Christopher J.; Eston, Michelle A.; Snapper, Scott B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Detre, Cynthia; Keszei, Marton; Terhorst, Cox] Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02215 USA. [Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA. [Alt, Frederick W.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Notarangelo, Luigi D.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Notarangelo, Luigi D.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. RP Snapper, SB (reprint author), Harvard Univ, Sch Med, Div Gastroenterol, Childrens Hosp Boston, 300 Longwood Ave, Boston, MA 02115 USA. EM lisa.westerberg@ki.se; scott.snapper@childrens.harvard.edu RI Dahlberg, Carin/N-1625-2013; Keszei, Marton/F-3295-2014; Notarangelo, Luigi/F-9718-2016; OI Dahlberg, Carin/0000-0002-8610-6302; Keszei, Marton/0000-0002-1158-2179; Notarangelo, Luigi/0000-0002-8335-0262; Westerberg, Lisa/0000-0003-2943-2192 FU Swedish Society for Medical Research; Swedish Research Council; National Institutes of Health [HL-59561, 2P30DK034854-26, AI-50950, DK-43351, AI-076210] FX This work was supported by a postdoctoral fellowship from the Swedish Society for Medical Research and research grants from the Swedish Research Council to L.S.W. and by the National Institutes of Health (grants HL-59561 to S.B.S. and L.D.N., 2P30DK034854-26 and AI-50950 to S.B.S., DK-43351 to S.B.S. and C.T., and AI-076210 to C.T. and L.D.N.). NR 34 TC 29 Z9 33 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 26 PY 2012 VL 119 IS 17 BP 3966 EP 3974 DI 10.1182/blood-2010-09-308197 PG 9 WC Hematology SC Hematology GA 959AU UT WOS:000305282900018 PM 22411869 ER PT J AU Psaila, B Bussel, JB Linden, MD Babula, B Li, YF Barnard, MR Tate, C Mathur, K Frelinger, AL Michelson, AD AF Psaila, Bethan Bussel, James B. Linden, Matthew D. Babula, Bracken Li, Youfu Barnard, Marc R. Tate, Chinara Mathur, Kanika Frelinger, Andrew L. Michelson, Alan D. TI In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation SO BLOOD LA English DT Article ID THROMBOPOIETIN RECEPTOR AGONIST; IB-IX COMPLEX; GLYCOPROTEIN-IB; CONTROLLED-TRIAL; DOUBLE-BLIND; REDISTRIBUTION; PURPURA; HETEROGENEITY; ROMIPLOSTIM; GROWTH AB The effects of eltrombopag, a thrombopoietin-receptor agonist, on platelet function in immune thrombocytopenia (ITP) are not fully characterized. This study used whole blood flow cytometry to examine platelet function in 20 patients receiving eltrombopag treatment at days 0, 7, and 28. Platelet surface expression of activated GPIIb/IIIa, P-selectin, and GPIb was measured with and without low and high adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) concentrations. Before eltrombopag treatment with no ex vivo agonist, platelet activation was higher in ITP patients than controls. Platelet GPIb and activated GPIIb/IIIa expression without added agonist was unchanged following eltrombopag treatment, whereas a slight increase in P-selectin was observed. Expression of P-selectin and activated GPIIb/IIIa in response to high-dose ADP was lower during eltrombopag treatment than at baseline. Eltrombopag led to a slight increase in platelet reactivity to TRAP only in responders to eltrombopag but not to levels above those in controls; whole blood experiments demonstrated that this increase was probably because of higher platelet counts rather than higher platelet reactivity. In conclusion, although thrombocytopenic ITP patients have higher baseline platelet activation than controls, eltrombopag did not cause platelet activation or hyper-reactivity, irrespective of whether the platelet count increased. (Blood. 2012;119(17): 4066-4072) C1 [Barnard, Marc R.; Frelinger, Andrew L.; Michelson, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Childrens Hosp Boston, Ctr Platelet Res Studies,Div Hematol Oncol, Boston, MA 02115 USA. [Linden, Matthew D.; Li, Youfu; Barnard, Marc R.; Frelinger, Andrew L.; Michelson, Alan D.] Univ Massachusetts, Sch Med, Dept Pediat, Ctr Platelet Funct Studies, Worcester, MA USA. [Psaila, Bethan] Imperial Coll Sch Med, London, England. [Psaila, Bethan; Bussel, James B.; Babula, Bracken; Tate, Chinara; Mathur, Kanika] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. RP Michelson, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Childrens Hosp Boston, Ctr Platelet Res Studies,Div Hematol Oncol, 300 Longwood Ave,Karp 08213, Boston, MA 02115 USA. EM alan.michelson@childrens.harvard.edu RI Linden, Matthew/G-9644-2012; OI Linden, Matthew/0000-0002-9126-2166; Psaila, Beth/0000-0001-8198-9663 FU Kay Kendall Leukaemia Fund traveling fellowship; Fulbright Scholarship for Cancer Research; National Institutes of Health [1U01 HL72196-01-05]; GlaxoSmithKline; Sysmex FX B.P. is the recipient of a Kay Kendall Leukaemia Fund traveling fellowship and a Fulbright Scholarship for Cancer Research, and J.B.B. receives funding from National Institutes of Health grant 1U01 HL72196-01-05. This study was partly supported by unrestricted grants from GlaxoSmithKline and Sysmex. NR 35 TC 25 Z9 29 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 26 PY 2012 VL 119 IS 17 BP 4066 EP 4072 DI 10.1182/blood-2011-11-393900 PG 7 WC Hematology SC Hematology GA 959AU UT WOS:000305282900029 PM 22294727 ER PT J AU Warlick, E Ahn, KW Pedersen, TL Artz, A de Lima, M Pulsipher, M Akpek, G Aljurf, M Cahn, JY Cairo, M Chen, YB Cooper, B Deol, A Giralt, S Gupta, V Khoury, HJ Kohrt, H Lazarus, HM Lewis, I Olsson, R Pidala, J Savani, BN Seftel, M Socie, G Tallman, M Ustun, C Vij, R Vindelov, L Weisdorf, D AF Warlick, Erica Ahn, Kwang Woo Pedersen, Tanya L. Artz, Andrew de Lima, Marcos Pulsipher, Michael Akpek, Gorgun Aljurf, Mahmoud Cahn, Jean-Yves Cairo, Mitchell Chen, Yi-Bin Cooper, Brenda Deol, Abhinav Giralt, Sergio Gupta, Vikas Khoury, H. Jean Kohrt, Holbrook Lazarus, Hillard M. Lewis, Ian Olsson, Richard Pidala, Joseph Savani, Bipin N. Seftel, Matthew Socie, Gerard Tallman, Martin Ustun, Celaettin Vij, Ravi Vindelov, Lars Weisdorf, Daniel TI Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC-PHASE; DONOR TRANSPLANTATION; IMATINIB-RESISTANT; FOLLOW-UP; DASATINIB; NILOTINIB; SURVIVAL; FAILURE; TRIALS AB Tyrosine kinase inhibitors (TKIs) and reduced intensity conditioning (RIC)/nonmyeloablative (NMA) conditioning hematopoietic cell transplants (HCTs) have changed the therapeutic strategy for chronic myelogenous leukemia (CML) patients. We analyzed post-HCT outcomes of 306 CML patients reported to the Center for International Blood and Marrow Transplant Research aged 40 years and older undergoing RIC/NMA HCT from 2001 to 2007: 117 (38%) aged 40 to 49 years, 119 (39%) 50 to 59 years, and 70 (23%) 60 years or older. The majority (74%) had treatment with imatinib before HCT. At HCT, most patients aged 40 to 49 years were in chronic phase (CP) 1 (74%), compared with 31% aged 60 years or older. Siblings were donors for 56% aged 40 to 49 years; older cohorts had more unrelated donors. The majority received peripheral blood grafts and RIC across all age groups. 3 year overall survival (54%, 52%, and 41%), day + 100 grade II-IV acute GVHD (26%, 32%, and 32%), chronic GVHD (58%, 51%, and 43%), and 1-year treatment-related mortality (18%, 20%, and 13%) were similar across ages. The 3-year relapse incidence (36%, 43%, and 66%) and disease-free survival (35%, 32%, and 16%) were inferior in the oldest cohort. Importantly, for CP1 patients, relapse and disease-free survival were similar across age cohorts. Allogeneic RIC HCT for older patients with CML can control relapse with acceptable toxicity and survival in TKI-exposed CML, especially if still in CP1. (Blood. 2012;119(17):4083-4090) C1 [Warlick, Erica; Ustun, Celaettin; Weisdorf, Daniel] Univ Minnesota, Div Hematol Oncol & Transplant, Minneapolis, MN 55455 USA. [Ahn, Kwang Woo] Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI USA. [Pedersen, Tanya L.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Artz, Andrew] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [de Lima, Marcos] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pulsipher, Michael] Utah Blood & Marrow Transplant Program, Salt Lake City, UT USA. [Akpek, Gorgun] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Aljurf, Mahmoud] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Cahn, Jean-Yves] Ctr Hosp Univ Grenoble, Hop Albert Michallon, Grenoble, France. [Cairo, Mitchell] New York Presbyterian Hosp, New York, NY USA. [Chen, Yi-Bin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cooper, Brenda; Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Deol, Abhinav] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Giralt, Sergio; Tallman, Martin] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Khoury, H. Jean] Emory Univ Hosp, Atlanta, GA 30322 USA. [Kohrt, Holbrook] Stanford Univ, Stanford Hosp & Clin, Med Ctr, Santa Clara, CA USA. [Lewis, Ian] Royal Adelaide Hosp, SA Pathol, Adelaide, SA 5000, Australia. [Olsson, Richard] Karolinska Univ Hosp, Stockholm, Sweden. [Pidala, Joseph] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Brentwood, TN USA. [Seftel, Matthew] Univ Manitoba, CancerCare Manitoba, Winnipeg, MB, Canada. [Socie, Gerard] Hop St Louis, Paris, France. [Vij, Ravi] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Vindelov, Lars] Rigshosp, DK-2100 Copenhagen, Denmark. RP Warlick, E (reprint author), Univ Minnesota, Div Hematol Oncol & Transplant, 420 Delaware St SE,Box 480,Mayo Bldg, Minneapolis, MN 55455 USA. EM ewarlick@umn.edu RI Cahn, Jean-Yves/M-6493-2014; OI Olsson, Richard/0000-0001-5970-2128 FU US Public Health Service from National Cancer Institute (NCI) [U24-CA76518, 5U01HL069294]; National Heart, Lung, and Blood Institute (NHLBI) [5U01HL069294]; National Institute of Allergy and Infectious Diseases; Health Resources and Services Administration [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB (National Blood Foundation); Allos Inc; Amgen Inc; Astellas Pharma US Inc; Be the Match Foundation; Biogen IDEC; Bio-Marin Pharmaceutical Inc; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix GmbH; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Eisai Inc; Genentech Inc; Genzyme Corporation; Histogenetics Inc; HKS Medical Information Systems; Hospira Inc; Kirin Brewery Co Ltd; The Leukemia & Lymphoma Society; Merck Company; Medical College of Wisconsin; Millennium Pharmaceuticals Inc; Miller Pharmacal Group; Milliman USA Inc; Miltenyi Biotec Inc; National Marrow Donor Program; Nature Publishing Group; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics Inc; Otsuka America Pharmaceutical Inc;; Pall Life Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau Pharmaceuticals; Soligenix Inc; StemCyte Inc; StemSoft Software Inc; Sysmex America Inc; THERAKOS Inc; Vidacare Corporation; ViraCor Laboratories; ViroPharma Inc; Wellpoint Inc FX The Center for Informational Blood and Marrow Transplant Research is supported by US Public Health Service grant/cooperative agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases; grant/cooperative agreement 5U01HL069294 from NHLBI and NCI; contract HHSH234200637015C with Health Resources and Services Administration; grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; grants from AABB (National Blood Foundation); Allos Inc; Amgen Inc; anonymous donation to the Medical College of Wisconsin; Astellas Pharma US Inc; Be the Match Foundation; Biogen IDEC; Bio-Marin Pharmaceutical Inc; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix GmbH; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Eisai Inc; Genentech Inc; Genzyme Corporation; Histogenetics Inc; HKS Medical Information Systems; Hospira Inc; Kirin Brewery Co Ltd; The Leukemia & Lymphoma Society; Merck & Company; The Medical College of Wisconsin; Millennium Pharmaceuticals Inc; Miller Pharmacal Group; Milliman USA Inc; Miltenyi Biotec Inc; National Marrow Donor Program; Nature Publishing Group; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics Inc; Otsuka America Pharmaceutical Inc; Pall Life Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau Pharmaceuticals; Soligenix Inc; StemCyte Inc; StemSoft Software Inc; Sysmex America Inc; THERAKOS Inc; Vidacare Corporation; ViraCor Laboratories; ViroPharma Inc; and Wellpoint Inc. NR 22 TC 25 Z9 25 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 26 PY 2012 VL 119 IS 17 BP 4083 EP 4090 DI 10.1182/blood-2012-02-409763 PG 8 WC Hematology SC Hematology GA 959AU UT WOS:000305282900031 PM 22408257 ER PT J AU Foley, P Levine, E Askew, S Puleo, E Whiteley, J Batch, B Heil, D Dix, D Lett, V Lanpher, M Miller, J Emmons, K Bennett, G AF Foley, Perry Levine, Erica Askew, Sandy Puleo, Elaine Whiteley, Jessica Batch, Bryan Heil, Daniel Dix, Daniel Lett, Veronica Lanpher, Michele Miller, Jade Emmons, Karen Bennett, Gary TI Weight gain prevention among black women in the rural community health center setting: The Shape Program SO BMC PUBLIC HEALTH LA English DT Article DE Obesity; Weight; eHealth; Women's health; Minority health; Primary care; Prevention ID BODY-MASS INDEX; RE-AIM FRAMEWORK; PERFORMANCE QUESTIONNAIRE HPQ; 3-FACTOR EATING QUESTIONNAIRE; PHYSICAL-ACTIVITY; AFRICAN-AMERICAN; SELF-EFFICACY; WHITE WOMEN; ORGANIZATION HEALTH; LOSS MAINTENANCE AB Background: Nearly 60% of black women are obese. Despite their increased risk of obesity and associated chronic diseases, black women have been underrepresented in clinical trials of weight loss interventions, particularly those conducted in the primary care setting. Further, existing obesity treatments are less effective for this population. The promotion of weight maintenance can be achieved at lower treatment intensity than can weight loss and holds promise in reducing obesity-associated chronic disease risk. Weight gain prevention may also be more consistent with the obesity-related sociocultural perspectives of black women than are traditional weight loss approaches. Methods/Design: We conducted an 18-month randomized controlled trial (the Shape Program) of a weight gain prevention intervention for overweight black female patients in the primary care setting. Participants include 194 premenopausal black women aged 25 to 44 years with a BMI of 25-34.9 kg/m(2). Participants were randomized either to usual care or to a 12-month intervention that consisted of: tailored obesogenic behavior change goals, self-monitoring via interactive voice response phone calls, tailored skills training materials, 12 counseling calls with a registered dietitian and a 12-month YMCA membership. Participants are followed over 18 months, with study visits at baseline, 6-, 12- and 18-months. Anthropometric data, blood pressure, fasting lipids, fasting glucose, and self-administered surveys are collected at each visit. Accelerometer data is collected at baseline and 12-months. At baseline, participants were an average of 35.4 years old with a mean body mass index of 30.2 kg/m(2). Participants were mostly employed and low-income. Almost half of the sample reported a diagnosis of hypertension or prehypertension and 12% reported a diagnosis of diabetes or prediabetes. Almost one-third of participants smoked and over 20% scored above the clinical threshold for depression. Discussion: The Shape Program utilizes an innovative intervention approach to lower the risk of obesity and obesity-associated chronic disease among black women in the primary care setting. The intervention was informed by behavior change theory and aims to prevent weight gain using inexpensive mobile technologies and existing health center resources. Baseline characteristics reflect a socioeconomically disadvantaged, high-risk population sample in need of evidence-based treatment strategies. C1 [Foley, Perry; Levine, Erica; Askew, Sandy; Dix, Daniel; Lett, Veronica; Lanpher, Michele; Miller, Jade; Bennett, Gary] Duke Global Hlth Inst, Duke Obes Prevent Program, Durham, NC 27705 USA. [Puleo, Elaine] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. [Whiteley, Jessica] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. [Batch, Bryan] Duke Univ, Med Ctr, Div Metab Endocrinol & Nutr, Durham, NC 27710 USA. [Dix, Daniel] Montana State Univ, Dept Hlth & Human Dev, Bozeman, MT 59717 USA. [Emmons, Karen] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Foley, P (reprint author), Duke Global Hlth Inst, Duke Obes Prevent Program, 2812 Erwin Rd,Suite 403 Box 90392, Durham, NC 27705 USA. EM perry.foley@duke.edu FU PHS health centers; [R01DK078798]; [K05CA124415]; [K22CA126992] FX This trial is funded by grant R01DK078798. Dr. Emmons was supported by K05CA124415 and Dr. Bennett was supported by K22CA126992. We express deep gratitude to the administration and staff of Piedmont Health for their continued collaboration and participation in the Shape Program. In particular, we would like to thank Brian Toomey, MSW, Tom Wroth, MD, MPH, Heather Miranda, RD, LDN, Marni Holder, RN, FNP-BC, Ashley Brewer, RD, LDN, Greg Wheatley, MPH, RD, LDN, Kristen Norton, MA, RD, LDN, Marianne Ratcliffe, MHA and staff at the PHS health centers for their support. We are grateful to Martha Zorn, MS at the University of Massachusetts-Amherst for her assistance with data analysis and to Lisa Englert for her assistance with manuscript preparation. Lastly, we would like to especially thank the women participating in Shape. NR 96 TC 15 Z9 15 U1 7 U2 46 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD APR 26 PY 2012 VL 12 AR 305 DI 10.1186/1471-2458-12-305 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 958YZ UT WOS:000305278200001 PM 22537222 ER PT J AU Everitt, AR Clare, S Pertel, T John, SP Wash, RS Smith, SE Chin, CR Feeley, EM Sims, JS Adams, DJ Wise, HM Kane, L Goulding, D Digard, P Anttila, V Baillie, JK Walsh, TS Hume, DA Palotie, A Xue, YL Colonna, V Tyler-Smith, C Dunning, J Gordon, SB Smyth, RL Openshaw, PJ Dougan, G Brass, AL Kellam, P AF Everitt, Aaron R. Clare, Simon Pertel, Thomas John, Sinu P. Wash, Rachael S. Smith, Sarah E. Chin, Christopher R. Feeley, Eric M. Sims, Jennifer S. Adams, David J. Wise, Helen M. Kane, Leanne Goulding, David Digard, Paul Anttila, Verneri Baillie, J. Kenneth Walsh, Tim S. Hume, David A. Palotie, Aarno Xue, Yali Colonna, Vincenza Tyler-Smith, Chris Dunning, Jake Gordon, Stephen B. Smyth, Rosalind L. Openshaw, Peter J. Dougan, Gordon Brass, Abraham L. Kellam, Paul CA GenISIS Investigators MOSAIC Investigators TI IFITM3 restricts the morbidity and mortality associated with influenza SO NATURE LA English DT Article ID INNATE IMMUNE-RESPONSE; WEST NILE VIRUS; A VIRUS; PANDEMIC VIRUS; DENGUE VIRUS; INFECTION; PROTEINS; PATHOGENESIS AB The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses(1-7). Both the magnitude and breadth of the IFITM proteins' in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model(8), we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 'Spanish' influenza(9,10). Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans. C1 [Everitt, Aaron R.; Clare, Simon; Wash, Rachael S.; Smith, Sarah E.; Adams, David J.; Kane, Leanne; Goulding, David; Anttila, Verneri; Palotie, Aarno; Xue, Yali; Colonna, Vincenza; Tyler-Smith, Chris; Dougan, Gordon; Kellam, Paul] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England. [Pertel, Thomas; John, Sinu P.; Chin, Christopher R.; Feeley, Eric M.; Sims, Jennifer S.; Brass, Abraham L.] MIT, Ragon Inst Massachusetts, Gen Hosp, Charlestown, MA 02129 USA. [Pertel, Thomas; John, Sinu P.; Chin, Christopher R.; Feeley, Eric M.; Sims, Jennifer S.; Brass, Abraham L.] Harvard Univ, Charlestown, MA 02129 USA. [Wise, Helen M.; Digard, Paul] Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England. [Baillie, J. Kenneth; Hume, David A.] Univ Edinburgh, Div Genet & Genom, Roslin Inst, Roslin EH25 9RG, Midlothian, Scotland. [Baillie, J. Kenneth; Walsh, Tim S.] Univ Edinburgh, Dept Crit Care Med, Edinburgh EH16 4TJ, Midlothian, Scotland. [Colonna, Vincenza] Natl Res Council CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy. [Dunning, Jake; Openshaw, Peter J.] Univ London Imperial Coll Sci Technol & Med, Ctr Resp Infect, Natl Heart & Lung Inst, London W2 1PG, England. [Gordon, Stephen B.] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. [Smyth, Rosalind L.] Univ Liverpool, Inst Translat Med, Alder Hey Childrens Hosp, Liverpool L12 2AP, Merseyside, England. [Brass, Abraham L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02117 USA. [Kellam, Paul] UCL, UCL MRC Ctr Med Mol Virol, Dept Infect, London W1T 4JF, England. RP Kellam, P (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England. EM abrass@partners.org; pk5@sanger.ac.uk RI Colonna, Vincenza/H-2021-2014; Digard, Paul/B-7717-2008; Johnston, Sebastian/I-2423-2012; Hume, David/C-7695-2013; Baillie, John Kenneth/F-3124-2011; Haley, Chris/F-3110-2013; Aylin, Paul/A-1073-2014; Hayward, Andrew/C-3268-2013; Semple, Malcolm/A-8790-2008; OI Herberg, Jethro/0000-0001-6941-6491; Aylin, Paul/0000-0003-4589-1743; Gordon, Stephen/0000-0001-6576-1116; Colonna, Vincenza/0000-0002-3966-0474; Nguyen-Van-Tam, Jonathan/0000-0003-2579-4655; Digard, Paul/0000-0002-0872-9440; Murphy, Lee/0000-0001-6467-7449; Baillie, John Kenneth/0000-0001-5258-793X; Hayward, Andrew/0000-0002-3549-6232; Semple, Malcolm/0000-0001-9700-0418; Smith, Sarah/0000-0001-8699-7670; Pertel, Thomas/0000-0002-2286-6011; Anttila, Verneri/0000-0002-0073-4675; McNamara, Paul/0000-0002-7055-6034 FU Wellcome Trust [090382/Z/09/Z]; Imperial's Comprehensive Biomedical Research Centre (cBRC); Medical Research Council UK; Chief Scientist Office (Scotland); Charles H. Hood Foundation; Phillip T. and Susan M. Ragon Institute Foundation; Bill and Melinda Gates Foundation; National Institute of Allergy and Infectious Diseases [R01AI091786]; Wellcome Trust through the Edinburgh Clinical Academic Track (ECAT) [090385/Z/09/Z]; Comprehensive Local Research Networks (CLRNs); National Institute for Health Research (NIHR), UK; Biomedical Research Centre (BRC); Unit (BRU) FX We would like to thank C. Brandt for maintaining mouse colony health and well-being and T. Hussell for provision of A/X-31 virus. We also thank D. Gurdasani and M. Sandhu for statistical analysis of genotype frequencies. We also thank M. Hu and I. Gallego Romero for calculating genome-wide selection statistics. This work was supported by the Wellcome Trust. The MOSAIC work was supported by Imperial's Comprehensive Biomedical Research Centre (cBRC), the Wellcome Trust (090382/Z/09/Z) and Medical Research Council UK. The GenISIS work was supported by the Chief Scientist Office (Scotland). A. L. B. is the recipient of a Charles H. Hood Foundation Child Health Research Award, and is supported by grants from the Phillip T. and Susan M. Ragon Institute Foundation, the Bill and Melinda Gates Foundation's Global Health Program and the National Institute of Allergy and Infectious Diseases (R01AI091786). J.K.B. is supported by a Wellcome Trust Clinical Lectureship (090385/Z/09/Z) through the Edinburgh Clinical Academic Track (ECAT). We acknowledge the assistance of K. Alshafi, E. Bailey, A. Bermingham, M. Berry, C. Bloom, E. Brannigan, S. Bremang, J. Clark, M. C. Cox, M. Cross, L. A. Cumming, S. Dyas, J. England-Smith, J. Enstone, D. Ferreira, N. Goddard, A. Godlee, S. Gormley, M. Guiver, M. O. Hassan-Ibrahim, H. Hill, P. Holloway, K. Hoschler, G. Houghton, F. Hughes, R. R. Israel, A. Jepson, K. D. Jones, W. P. Kelleher, M. Kidd, K. Knox, A. Lackenby, G. Lloyd, H. Longworth, M. Minns, S. Mookerjee, S. Mt-Isa, D. Muir, A. Paras, V. Pascual, L. Rae, S. Rodenhurst, F. Rozakeas, E. Scott, E. Sergi, N. Shah, V. Sutton, J. Vernazza, A. W. Walker, C. Wenden, T. Wotherspoon, A. D. Wright, F. Wurie and the clinical and laboratory staff of the Alder Hey Children's NHS Foundation Trust, Brighton & Sussex University Hospitals NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, Chelsea and Westminster Hospital NHS Foundation Trust, Alder Hey Children's Hospital and Liverpool School of Tropical Medicine, Health Protection Agency Microbiology Services Colindale, Imperial College Healthcare NHS Trust, Liverpool Women's NHS Foundation Trust, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Royal Brompton and Harefield NHS Foundation Trust, The Roslin Institute, Edinburgh, University Hospitals Coventry and Warwickshire NHS Trust. The MOSAIC consortium was supported by several Comprehensive Local Research Networks (CLRNs), the National Institute for Health Research (NIHR), UK, and by the Biomedical Research Centre (BRC) and Unit (BRU) funds. Finally, we thank all patients and their relatives for their generous agreement to inclusion in this study. NR 33 TC 245 Z9 257 U1 5 U2 53 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 26 PY 2012 VL 484 IS 7395 BP 519 EP U146 DI 10.1038/nature10921 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 931FF UT WOS:000303200400052 PM 22446628 ER PT J AU Puig, A Mino-Kenudson, M Dighe, AS AF Puig, Alberto Mino-Kenudson, Mari Dighe, Anand S. TI Case 13-2012: A 62-Year-Old Man with Paresthesias, Weight Loss, Jaundice, and Anemia Vitamin B-12 deficiency due to pernicious anemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 [Puig, Alberto] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Mino-Kenudson, Mari; Dighe, Anand S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Puig, Alberto] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mino-Kenudson, Mari; Dighe, Anand S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Puig, A (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 14 TC 3 Z9 3 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 26 PY 2012 VL 366 IS 17 BP 1626 EP 1633 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 931FC UT WOS:000303200100013 PM 22533579 ER PT J AU Stone, JH Zen, Y Deshpande, V AF Stone, John H. Zen, Yoh Deshpande, Vikram TI IgG4-Related Disease REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Stone, John H.; Deshpande, Vikram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zen, Yoh] Kings Coll Hosp London, London, England. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jhstone@partners.org NR 3 TC 1 Z9 1 U1 2 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 26 PY 2012 VL 366 IS 17 BP 1646 EP 1647 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 931FC UT WOS:000303200100032 ER PT J AU Nishino, M Van Cott, EM Kotton, DN AF Nishino, Michiya Van Cott, Elizabeth M. Kotton, Darrell N. TI Case 2-2012: Dyspnea and Rapidly Progressive Respiratory Failure REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID KASABACH-MERRITT PHENOMENON; HEMANGIOMA C1 [Nishino, Michiya; Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kotton, Darrell N.] Boston Med Ctr, Boston, MA USA. RP Nishino, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 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 APR 26 PY 2012 VL 366 IS 17 BP 1647 EP 1648 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 931FC UT WOS:000303200100034 ER PT J AU Hata, S Taniguchi, M Yi, PA Ikeuchi, T Fagan, AM Holtzman, DM Bateman, R Sohrabi, HR Martins, RN Gandy, S Urakami, K Suzuki, T AF Hata, Saori Taniguchi, Miyako Yi Piao Ikeuchi, Takeshi Fagan, Anne M. Holtzman, David M. Bateman, Randall Sohrabi, Hamid R. Martins, Ralph N. Gandy, Sam Urakami, Katsuya Suzuki, Toshiharu CA Japanese Alzheimers Dis TI Multiple gamma-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer's disease subjects SO MOLECULAR NEURODEGENERATION LA English DT Article DE Alzheimer's disease; Cerebrospinal fluid; gamma-secretase; Alcadein; beta-amyloid ID BETA-PROTEIN PRECURSOR; AMYLOID DEPOSITION; IN-VIVO; PHOSPHORYLATION; METABOLISM; A-BETA(42); MUTATIONS; BINDING; PLASMA AB Background: Alcadein(alpha) (Alc(alpha)) is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-beta precursor protein (APP). Successive cleavage of APP by beta- and gamma-secretases generates the aggregatable amyloid-beta peptide (A beta), while cleavage of APP or Alc(alpha) by alpha- and gamma-secretases generates non-aggregatable p3 or p3-Alc(alpha) peptides. A beta and p3-Alc(alpha) can be recovered from human cerebrospinal fluid (CSF). We have previously reported alternative processing of APP and Alc(alpha) in the CSF of some patients with sporadic mild cognitive impairment (MCI) and AD (SAD). Results: Using the sandwich enzyme-linked immunosorbent assay (ELISA) system that detects total p3-Alc(alpha), we determined levels of total p3-Alc(alpha) in CSF from subjects in one of four diagnostic categories (elderly controls, MCI, SAD, or other neurological disease) derived from three independent cohorts. Levels of A beta 40 correlated with levels of total p3-Alc(alpha) in all cohorts. Conclusions: We confirm that A beta 40 is the most abundant A beta species, and we propose a model in which CSF p3-Alc(alpha) can serve as a either (1) a nonaggregatable surrogate marker for gamma-secretase activity; (2) as a marker for clearance of transmembrane domain peptides derived from integral protein catabolism; or (3) both. We propose the specification of an MCI/SAD endophenotype characterized by co-elevation of levels of both CSF p3-Alc(alpha) and A beta 40, and we propose that subjects in this category might be especially responsive to therapeutics aimed at modulation of gamma-secretase function and/or transmembrane domain peptide clearance. These peptides may also be used to monitor the efficacy of therapeutics that target these steps in A beta metabolism. C1 [Hata, Saori; Yi Piao; Suzuki, Toshiharu] Hokkaido Univ, Grad Sch Pharmaceut Sci, Neurosci Lab, Sapporo, Hokkaido, Japan. [Taniguchi, Miyako; Urakami, Katsuya] Tottori Univ, Fac Med, Sch Hlth Sci, Dept Biol Regulat, Yonago, Tottori 683, Japan. [Ikeuchi, Takeshi] Niigata Univ, Brain Res Inst, Dept Mol Neurosci, Niigata, Japan. [Fagan, Anne M.; Holtzman, David M.; Bateman, Randall] Washington Univ, Sch Med, Dept Neurol, Alzheimers Dis Res Ctr, St Louis, MO 63110 USA. [Sohrabi, Hamid R.; Martins, Ralph N.] Edith Cowan Univ, Sch Exercise Biomed & Hlth Sci, Ctr Excellence Alzheimers Dis Res & Care, Joondalup, WA, Australia. [Gandy, Sam] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY USA. [Gandy, Sam] James J Peters Vet Adm Med Ctr, Bronx, NY USA. RP Suzuki, T (reprint author), Hokkaido Univ, Grad Sch Pharmaceut Sci, Neurosci Lab, Sapporo, Hokkaido, Japan. EM tsuzuki@pharm.hokudai.ac.jp RI Hata, Saori /A-3829-2012; Suzuki, Toshiharu/B-5342-2013; Sohrabi, Hamid Reza/D-2744-2013; Sohrabi, Hamid R Sohrabi/L-2461-2016 OI Sohrabi, Hamid Reza/0000-0001-8017-8682; Sohrabi, Hamid R Sohrabi/0000-0001-8017-8682 FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) [20390018, 22890001]; Ministry of Health, Labor and Welfare (MHLW); New Energy and Industrial Technology Development Organization (NEDO) in Japan; Northern Advancement Center for Science & Technology (NOASTEC); Terumo Life Science Foundation; NIA Alzheimer's Disease Research Center [P50 005138]; National Center for Research Resources (NCRR) [UL1 RR024992]; Veterans Administration; [P50 AG05681]; [P01-AG03991]; [P01-AG26276] FX This work was supported in part by Grants-in-Aid for Scientific Research (20390018 to TS) and Grant-in-Aid for Research Activity Start-up (22890001 to SH) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), a grant from the Ministry of Health, Labor and Welfare (MHLW), and a grant from the New Energy and Industrial Technology Development Organization (NEDO) in Japan. S.H. was supported by Northern Advancement Center for Science & Technology (NOASTEC) and Terumo Life Science Foundation. S.G. was supported by the NIA Alzheimer's Disease Research Center grant P50 005138 to Mary Sano and by the Veterans Administration. The Washington University in St Louis Alzheimer's Disease Center Biomarker Core is supported by P50 AG05681 [J.C.M.], P01-AG03991 [J.C.M.], P01-AG26276 [J.C.M.]. This publication was made possible by Grant Number UL1 RR024992 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. NR 31 TC 8 Z9 8 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PD APR 25 PY 2012 VL 7 AR 16 DI 10.1186/1750-1326-7-16 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 993FH UT WOS:000307840900001 PM 22534039 ER PT J AU Mukerji, J Olivieri, KC Misra, V Agopian, KA Gabuzda, D AF Mukerji, Joya Olivieri, Kevin C. Misra, Vikas Agopian, Kristin A. Gabuzda, Dana TI Proteomic analysis of HIV-1 Nef cellular binding partners reveals a role for exocyst complex proteins in mediating enhancement of intercellular nanotube formation SO RETROVIROLOGY LA English DT Article DE HIV; Nef; Exocyst complex; Intercellular nanotubes; Pak2 kinase; Fluorescence confocal microscopy ID VIRUS TYPE-1 NEF; NF-KAPPA-B; T-CELLS; P21-ACTIVATED KINASE-2; INFECTED-CELLS; LIPID RAFTS; IMMUNOLOGICAL SYNAPSE; MULTIVESICULAR BODIES; DENDRITIC CELLS; IN-VIVO AB Background: HIV-1 Nef protein contributes to pathogenesis via multiple functions that include enhancement of viral replication and infectivity, alteration of intracellular trafficking, and modulation of cellular signaling pathways. Nef stimulates formation of tunneling nanotubes and virological synapses, and is transferred to bystander cells via these intercellular contacts and secreted microvesicles. Nef associates with and activates Pak2, a kinase that regulates T-cell signaling and actin cytoskeleton dynamics, but how Nef promotes nanotube formation is unknown. Results: To identify Nef binding partners involved in Pak2-association dependent Nef functions, we employed tandem mass spectrometry analysis of Nef immunocomplexes from Jurkat cells expressing wild-type Nef or Nef mutants defective for the ability to associate with Pak2 (F85L, F89H, H191F and A72P, A75P in NL4-3). We report that wild-type, but not mutant Nef, was associated with 5 components of the exocyst complex (EXOC1, EXOC2, EXOC3, EXOC4, and EXOC6), an octameric complex that tethers vesicles at the plasma membrane, regulates polarized exocytosis, and recruits membranes and proteins required for nanotube formation. Additionally, Pak2 kinase was associated exclusively with wild-type Nef. Association of EXOC1, EXOC2, EXOC3, and EXOC4 with wild-type, but not mutant Nef, was verified by co-immunoprecipitation assays in Jurkat cells. Furthermore, shRNA-mediated depletion of EXOC2 in Jurkat cells abrogated Nef-mediated enhancement of nanotube formation. Using bioinformatic tools, we visualized protein interaction networks that reveal functional linkages between Nef, the exocyst complex, and the cellular endocytic and exocytic trafficking machinery. Conclusions: Exocyst complex proteins are likely a key effector of Nef-mediated enhancement of nanotube formation, and possibly microvesicle secretion. Linkages revealed between Nef and the exocyst complex suggest a new paradigm of exocyst involvement in polarized targeting for intercellular transfer of viral proteins and viruses. C1 [Mukerji, Joya; Olivieri, Kevin C.; Misra, Vikas; Agopian, Kristin A.; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Mukerji, Joya; Agopian, Kristin A.; Gabuzda, Dana] Harvard Univ, Sch Med, Div Med Sci Program Virol, Boston, MA USA. [Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol Microbiol, Boston, MA USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIH [R21 AI73415, R21 AI77464, DP1 DA028994]; Harvard University Center for AIDS Research; DFCI/Harvard Cancer Center; [T32 AG00222]; [T32 AI007386] FX We thank Stefanie Sowinski, Mathew Sowa, Wei Guo, Edward Manser, Michael Farzan, Thomas M. Roberts, Kai Wucherpfennig, Etienne Gagnon, Ross Tomaino, David Cureton, Lai Ding, Jeffrey Teigler, Daniel Tom, Lisa Cameron, Megan Mefford, Alexander Holman, Andres Finzi, Hillel Haim, and the Gabuzda Lab for advice and discussions, Ross Tomaino for mass spectrometry and data analysis, Lai Ding and Daniel Tom for expert confocal imaging support, and Peter Schow and Kimberley Lowe for FACS. This work was supported by NIH grants R21 AI73415, R21 AI77464, and DP1 DA028994. pHAGE was obtained from the Harvard Gene Therapy Initiative plasmid repository. J.M. was supported in part by T32 AG00222. K.C.O. was supported in part by T32 AI007386. Core facilities were supported by Harvard University Center for AIDS Research, and DFCI/Harvard Cancer Center grants. Confocal microscopy images were collected by J.M. at the Harvard NeuroDiscovery Center Optical Imaging Core Facility. NR 94 TC 33 Z9 33 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD APR 25 PY 2012 VL 9 AR 33 DI 10.1186/1742-4690-9-33 PG 16 WC Virology SC Virology GA 967HP UT WOS:000305897800001 PM 22534017 ER PT J AU Perkins, BA Rabbani, N Weston, A Ficociello, LH Adaikalakoteswari, A Niewczas, M Warram, J Krolewski, AS Thornalley, P AF Perkins, Bruce A. Rabbani, Naila Weston, Andrew Ficociello, Linda H. Adaikalakoteswari, Antonysunil Niewczas, Monika Warram, James Krolewski, Andrzej S. Thornalley, Paul TI Serum Levels of Advanced Glycation Endproducts and Other Markers of Protein Damage in Early Diabetic Nephropathy in Type 1 Diabetes SO PLOS ONE LA English DT Article ID RENAL-FUNCTION DECLINE; DEGRADATION-PRODUCTS; END-PRODUCTS; MICROALBUMINURIA; COMPLICATIONS; RISK; MELLITUS; ALBUMIN; CARBOXYMETHYLLYSINE; OXIDATION AB Objective: To determine the role of markers of plasma protein damage by glycation, oxidation and nitration in microalbuminuria onset or subsequent decline of glomerular filtration rate (termed "early GFR decline") in patients with type 1 diabetes. Methods: From the 1st Joslin Kidney Study, we selected 30 patients with longstanding normoalbuminuria and 55 patients with new onset microalbuminuria. Patients with microalbuminuria had 8-12 years follow-up during which 33 had stable GFR and 22 early GFR decline. Mean baseline GFR(CYSTATIN C) was similar between the three groups. Glycation, oxidation and nitration markers were measured in protein and ultrafiltrate at baseline by liquid chromatography-tandem mass spectrometry using the most reliable methods currently available. Results: Though none were significantly different between patients with microalbuminuria with stable or early GFR decline, levels of 6 protein damage adduct residues of plasma protein and 4 related free adducts of plasma ultrafiltrate were significantly different in patients with microalbuminuria compared to normoalbuminuria controls. Three protein damage adduct residues were decreased and 3 increased in microalbuminuria while 3 free adducts were decreased and one increased in microalbuminuria. The most profound differences were of N-formylkynurenine (NFK) protein adduct residue and N-omega-carboxymethylarginine (CMA) free adduct in which levels were markedly lower in microalbuminuria (P<0.001 for both). Conclusions: Complex processes influence levels of plasma protein damage and related proteolysis product free adducts in type 1 diabetes and microalbuminuria. The effects observed point to the possibility that patients who have efficient mechanisms of disposal of damaged proteins might be at an increased risk of developing microalbuminuria but not early renal function decline. The findings support the concept that the mechanisms responsible for microalbuminuria may differ from the mechanisms involved in the initiation of early renal function decline. C1 [Perkins, Bruce A.] Univ Toronto, Div Endocrinol, Toronto, ON, Canada. [Rabbani, Naila; Weston, Andrew; Adaikalakoteswari, Antonysunil; Thornalley, Paul] Univ Warwick, Warwick Med Sch, Clin Sci Res Inst, Coventry CV4 7AL, W Midlands, England. [Ficociello, Linda H.; Niewczas, Monika; Warram, James; Krolewski, Andrzej S.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. RP Perkins, BA (reprint author), Univ Toronto, Div Endocrinol, Toronto, ON, Canada. EM bruce.perkins@uhn.on.ca FU National Institutes of Health [DK041526, DK067638]; Joslin Diabetes Center; Banting and Best Diabetes Center FX This research was supported by National Institutes of Health grants DK041526, DK067638 (to AK) and the Joslin Diabetes Center. BAP was a Canadian Diabetes Association Scholar and was supported by the Banting and Best Diabetes Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 21 Z9 24 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 25 PY 2012 VL 7 IS 4 AR e35655 DI 10.1371/journal.pone.0035655 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959VP UT WOS:000305345200062 PM 22558190 ER PT J AU Rodgers, MA Villareal, VA Schaefer, EA Peng, LF Corey, KE Chung, RT Yang, PL AF Rodgers, Mary A. Villareal, Valerie A. Schaefer, Esperance A. Peng, Lee F. Corey, Kathleen E. Chung, Raymond T. Yang, Priscilla L. TI Lipid Metabolite Profiling Identifies Desmosterol Metabolism as a New Antiviral Target for Hepatitis C Virus SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RNA REPLICATION; GENE-EXPRESSION; CORE PROTEIN; CELL-CULTURE; INFECTION; CHOLESTEROL; HOST; BIOSYNTHESIS; THERAPY AB Hepatitis C virus (HCV) infection has been clinically associated with serum lipid abnormalities, yet our understanding of the effects of HCV on host lipid metabolism and conversely the function of individual lipids in HCV replication remains incomplete. Using liquid chromatography-mass spectrometry metabolite profiling of the HCV JFH1 cell culture infection model, we identified a significant steady-state accumulation of desmosterol, an immediate precursor to cholesterol. Pharmacological inhibition or RNAi-mediated depletion of DHCR7 significantly reduced steady-state HCV protein expression and viral genomic RNA. Moreover, this effect was reversed when cultures were supplemented with exogenous desmosterol. Together, these observations suggest an intimate connection between HCV replication and desmosterol homeostasis and that the enzymes responsible for synthesis of desmosterol may be novel targets for antiviral design. C1 [Rodgers, Mary A.; Villareal, Valerie A.; Yang, Priscilla L.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Schaefer, Esperance A.; Peng, Lee F.; Corey, Kathleen E.; Chung, Raymond T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. RP Yang, PL (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, 200 Longwood Ave, Boston, MA 02115 USA. EM priscilla_yang@hms.harvard.edu FU Harvard University Office of Faculty Development and Diversity; John and Virginia Kaneb Fellowship; NIH [R21AI068999, R01AI076442, NIH R01AI076442, AI069939, AI082630, 1K08DK088951-01]; Karnovsky Foundation; Taplin Funds for Discovery Program FX This work was supported by a Research Enabling Grant from the Harvard University Office of Faculty Development and Diversity, a John and Virginia Kaneb Fellowship, NIH R21AI068999 and R01AI076442 (P.L.Y.), NIH Diversity Supplement to NIH R01AI076442 (P.L.Y., V.A.V.), NIH AI069939 and AI082630 (R.T.C.), 1K08DK088951-01 (L.F.P.), and a fellowship from the Karnovsky Foundation (M.A.R.). LC/MS data were acquired on an Agilent 6520 Q-TOF spectrophotometer supported by the Taplin Funds for Discovery Program (S. Walker). Huh7.5, JFH1, and 9E10 antibody were gifts from Dr. Charles Rice (Rockefeller University) via Apath LLC; Huh7.5.1 cells were a gift from Dr. Francis V. Chisari (The Scripps Research Institute); JFH1 was also a kind gift from Dr. Takaji Wakita (National Institute of Infectious Diseases, Japan). Purified anti-HCV core antibody used in Western blot experiments by L.F.P. and E.K.S. was produced from the anti-HCV core 6G7 hybridoma cells generously provided by Dr. Abe Brass, Massachusetts General Hospital. Dengue virus (serotype 2) core antibody was produced from hybridoma cell line 6f3.1, kindly provided by Dr. John Aaskov. We thank N. S. Gray, C. T. Walsh, A. Saghatelian, and members of the Yang research group for helpful discussions. NR 31 TC 26 Z9 27 U1 0 U2 13 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 APR 25 PY 2012 VL 134 IS 16 BP 6896 EP 6899 DI 10.1021/ja207391q PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 930LB UT WOS:000303139800003 PM 22480142 ER PT J AU Adler-Milstein, J Jha, AK AF Adler-Milstein, Julia Jha, Ashish K. TI Sharing Clinical Data Electronically A Critical Challenge for Fixing the Health Care System SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID INFORMATION EXCHANGE; HOSPITALS C1 [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Sch Med, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. [Adler-Milstein, Julia] Univ Michigan, Ann Arbor, MI 48109 USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Sch Med, 665 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu NR 8 TC 28 Z9 28 U1 3 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 25 PY 2012 VL 307 IS 16 BP 1695 EP 1696 DI 10.1001/jama.2012.525 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 930OA UT WOS:000303147500019 PM 22535851 ER PT J AU Bongiovanni, M Krane, JF Cibas, ES Faquin, WC AF Bongiovanni, Massimo Krane, Jeffrey F. Cibas, Edmund S. Faquin, William C. TI The atypical thyroid fine-needle aspiration: Past, present, and future SO CANCER CYTOPATHOLOGY LA English DT Review DE thyroid; fine-needle aspiration; atypia; atypia of undetermined significance; follicular lesion of undetermined significance (AUS; FLUS); Bethesda ID CYTOLOGICALLY INDETERMINATE LESIONS; CANDIDATE DIAGNOSTIC MARKERS; COMBINED CLINICAL FACTORS; UNDETERMINED SIGNIFICANCE; BETHESDA SYSTEM; MALIGNANCY RISK; FOLLICULAR NEOPLASM; PAPILLARY CARCINOMA; SCIENCE CONFERENCE; FOLLOW-UP AB Thyroid fine-needle aspiration has developed into a key test in the evaluation of thyroid nodules. Although the interpretation of thyroid aspirates containing mild abnormalities is problematic, the introduction of the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category in The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has helped to delineate such cases in a systematic and clinically meaningful manner. Herein the authors review the cytomorphologic features associated with the AUS/FLUS interpretation and summarize the results of studies conducted since the implementation of TBSRTC. Cancer (Cancer Cytopathol) 2012;. (c) 2011 American Cancer Society. C1 [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bongiovanni, Massimo] Inst Pathol, Locarno, Switzerland. [Krane, Jeffrey F.; Cibas, Edmund S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@partners.org RI Bongiovanni, Massimo/C-3144-2017 OI Bongiovanni, Massimo/0000-0001-9846-6682 NR 60 TC 41 Z9 43 U1 0 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2012 VL 120 IS 2 BP 73 EP 86 DI 10.1002/cncy.20178 PG 14 WC Oncology; Pathology SC Oncology; Pathology GA 925XU UT WOS:000302796500002 PM 21751429 ER PT J AU Wilbur, DC AF Wilbur, David C. TI Cervical cytology screening programs: Similarities and differences between the United States and United Kingdom systems SO CANCER CYTOPATHOLOGY LA English DT Editorial Material C1 [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wilbur, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Wilbur, DC (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM dwilbur@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2012 VL 120 IS 2 BP 102 EP 104 DI 10.1002/cncy.20202 PG 3 WC Oncology; Pathology SC Oncology; Pathology GA 925XU UT WOS:000302796500005 PM 22367853 ER PT J AU Krane, JF VanderLaan, PA Faquin, WC Renshaw, AA AF Krane, Jeffrey F. VanderLaan, Paul A. Faquin, William C. Renshaw, Andrew A. TI The atypia of undetermined significance/follicular lesion of undetermined significance:malignant ratio SO CANCER CYTOPATHOLOGY LA English DT Article DE thyroid gland; fine-needle aspiration; thyroid nodule; health care quality assurance; atypia; atypia of undetermined significance; follicular lesion of undetermined significance (AUS); Bethesda. ID FINE-NEEDLE-ASPIRATION; REPORTING THYROID CYTOPATHOLOGY; CYTOLOGICALLY INDETERMINATE LESIONS; MALIGNANCY RISK; BETHESDA SYSTEM; FOLLICULAR LESION; RATES; CELLS AB BACKGROUND: The Bethesda System (TBS) for reporting thyroid cytopathology introduced the atypia of undetermined significance/follicular lesion of undetermined significance (AUS) category, but did not provide adequate guidance for the appropriate use of this diagnosis. In the current study, the authors sought to identify an appropriate measure for AUS use based on experience to date with TBS. METHODS: The authors reviewed 8 series, including their own laboratory experiences, with a total of 30,466 thyroid aspirates classified within TBS. RESULTS: The median AUS rate was 9.9% with a range of 3.0% to 18.0%. Use of the individual diagnostic categories within TBS varied up to 12.7-fold. The ratio of "suspicious for follicular neoplasm" plus "suspicious for malignancy" to "malignant" (M) diagnoses varied the least (1.8-fold). The AUS: M ratio provided a suitable measure of assessing AUS use, with a median ratio of 2.0 and a range of 0.5 to 4.9. CONCLUSIONS: Based on available studies, an AUS: M ratio of 1.0 to 3.0 is recommended. AUS: M ratios > 3.0 are likely because of overdiagnosis of AUS or underdiagnosis of M. AUS: M ratios < 1.0 are mostly due to low AUS rates, at the likely expense of sensitivity. Cancer (Cancer Cytopathol) 2012; 120: 111-6. (C) 2011 American Cancer Society. C1 [Krane, Jeffrey F.; VanderLaan, Paul A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Renshaw, Andrew A.] Baptist Hosp Miami, Dept Pathol, Miami, FL USA. RP Krane, JF (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jkrane@partners.org OI VanderLaan, Paul/0000-0002-7234-5652 NR 17 TC 44 Z9 44 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2012 VL 120 IS 2 BP 111 EP 116 DI 10.1002/cncy.20192 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA 925XU UT WOS:000302796500008 PM 21919213 ER PT J AU Bongiovanni, M Crippa, S Baloch, Z Piana, S Spitale, A Pagni, F Mazzucchelli, L Di Bella, C Faquin, W AF Bongiovanni, Massimo Crippa, Stefano Baloch, Zubair Piana, Simonetta Spitale, Alessandra Pagni, Fabio Mazzucchelli, Luca Di Bella, Camillo Faquin, William TI Comparison of 5-tiered and 6-tiered diagnostic systems for the reporting of thyroid cytopathology SO CANCER CYTOPATHOLOGY LA English DT Article DE thyroid; fine-needle aspiration; reporting system; Bethesda; Italian Society for Anatomic Pathology and Cytopathology-International Academy of Pathology (SIAPEC-IAP) ID FINE-NEEDLE-ASPIRATION; BETHESDA SYSTEM; CYTOLOGY; NODULES; TERMINOLOGY; GUIDELINES; MANAGEMENT; BIOPSIES; CANCER; VARIABILITY AB BACKGROUND: At present, thyroid fine-needle aspiration (FNA) specimens are diagnosed using a tiered classification scheme, with the most popular of these being the 5-tiered and 6-tiered systems. In this study, the authors present their institutional experiences using these 2 different systems and evaluate their efficacy based on the surgical follow-up. METHODS: Thyroid FNA specimens and their corresponding surgical resection specimens were collected between 2007 and 2009. The following diagnostic categories are used in both systems: unsatisfactory/nondiagnostic, benign, follicular neoplasm/suspicious for follicular neoplasm, suspicious for malignancy, and malignant. An additional category termed atypia of undetermined significance/follicular lesion of undetermined significance was used for atypical cases in the 6-tiered system. Statistical analysis was performed by comparing the different diagnostic categories. RESULTS: The case cohort included a total of 7686 thyroid FNA specimens representing 3962 nodules and 3724 nodules, respectively, in the 5-tiered and 6-tiered systems. Negative predictive values for the benign categories (96.9% vs 97.5%; P = 1) and positive predictive values for both the follicular neoplasm categories (26.5% vs 32.1%; P.2531) and the malignant categories (99.1% vs 99.4%; P = 1) were similar. The most significant differences between the 5-tiered and 6-tiered systems were the percentage of cases classified as benign (83.9% vs 55.4%; P <.0001) and as follicular neoplasms (4.6% vs 23.8%; P <.0001). It is interesting to note that fewer patients were referred for surgery in the 5-tiered system compared with the 6-tiered one (9.1% vs 36.5%; P <.0001). CONCLUSIONS: Use of either the 5-tiered or 6-tiered reporting systems for thyroid FNA specimens can potentially affect the clinical management of patients with thyroid nodules. Cancer (Cancer Cytopathol) 2012; 120: 117-25. (C) 2011 American Cancer Society. C1 [Bongiovanni, Massimo; Crippa, Stefano; Spitale, Alessandra; Mazzucchelli, Luca] Inst Pathol, CH-6600 Locarno, Switzerland. [Baloch, Zubair] Univ Penn, Dept Pathol, Med Ctr, Philadelphia, PA 19104 USA. [Piana, Simonetta] Arcispedale Santa Maria Nuova, Dept Pathol, Reggio Emilia, Italy. [Pagni, Fabio; Di Bella, Camillo] Desio Hosp, Dept Pathol, Desio, Italy. [Faquin, William] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Bongiovanni, M (reprint author), Inst Pathol, Via Selva 24, CH-6600 Locarno, Switzerland. EM massimo.bongiovanni@ti.ch RI Bongiovanni, Massimo/C-3144-2017; OI Bongiovanni, Massimo/0000-0001-9846-6682; Pagni, Fabio/0000-0001-9625-1637 NR 34 TC 32 Z9 32 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2012 VL 120 IS 2 BP 117 EP 125 DI 10.1002/cncy.20195 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 925XU UT WOS:000302796500009 PM 21998003 ER PT J AU Ruff, CT AF Ruff, Christian T. TI Stroke Prevention in Atrial Fibrillation SO CIRCULATION LA English DT Editorial Material C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. RP Ruff, CT (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM cruff@partners.org NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 24 PY 2012 VL 125 IS 16 BP E588 EP E590 DI 10.1161/CIRCULATIONAHA.111.067843 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981GP UT WOS:000306955300001 PM 22529067 ER PT J AU Abramson, DH Marr, BP Brodie, SE Dunkel, I Palioura, S Gobin, YP AF Abramson, David H. Marr, Brian P. Brodie, Scott E. Dunkel, Ira Palioura, Sotiria Gobin, Y. Pierre TI Ophthalmic Artery Chemosurgery for Less Advanced Intraocular Retinoblastoma: Five Year Review SO PLOS ONE LA English DT Review ID BILATERAL RETINOBLASTOMA; RADIATION-THERAPY; CHEMOTHERAPY; MANAGEMENT; CHEMOREDUCTION; RADIOTHERAPY; OTOTOXICITY; FAILURE AB Background: Ophthalmic artery chemosurgery (OAC) for retinoblastoma was introduced by us 5 years ago for advanced intraocular retinoblastoma. Because the success was higher than with existing alternatives and systemic side effects limited we have now treated less advanced intraocular retinoblastoma (Reese-Ellsworth (RE) I-III and International Classification Retinoblastoma (ICRB) B and C). Methodology/Principal Findings: Retrospective review of 5 year experience in eyes with Reese Ellsworth (Table 1) I (7 eyes), II (6 eyes) or III (6 eyes) and/or International Classification (Table 2) B (19 eyes) and C (11 eyes) treated with OAC (melphalan with or without topotecan) introduced directly into the ophthalmic artery. Patient survival was 100%. Ocular event-free survival was 100% for Reese-Ellsworth Groups I, II and III (and 96% for ICRB B and C) at a median of 16 months follow-up. One ICRB Group C (Reese-Ellsworth Vb) eye could not be treated on the second attempt for technical reasons and was therefore enucleated. No patient required a port and only one patient required transfusion of blood products. The electroretinogram (ERG) was unchanged or improved in 14/19 eyes. Conclusions/Significance: Ophthalmic artery chemosurgery for retinoblastoma that was Reese-Ellsworth I, II and III (or International Classification B or C) was associated with high success (100% of treatable eyes were retained) and limited toxicity with results that equal or exceed conventional therapy with less toxicity. C1 [Abramson, David H.; Marr, Brian P.; Brodie, Scott E.; Palioura, Sotiria] Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10021 USA. [Brodie, Scott E.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Dunkel, Ira] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Palioura, Sotiria] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Gobin, Y. Pierre] Weill Cornell Med Coll, Dept Radiol, New York, NY USA. [Gobin, Y. Pierre] Weill Cornell Med Coll, Dept Neurosurg, New York, NY USA. RP Abramson, DH (reprint author), Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, 1275 York Ave, New York, NY 10021 USA. EM abramsod@mskcc.org OI Dunkel, Ira/0000-0001-8091-6067 FU Fund for Ophthalmic Knowledge; Alcon Research Institute FX This work was supported by grants from the Fund for Ophthalmic Knowledge and the Alcon Research Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 23 Z9 25 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 24 PY 2012 VL 7 IS 4 AR e34120 DI 10.1371/journal.pone.0034120 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959VE UT WOS:000305343200003 PM 22545080 ER PT J AU Njauw, CNJ Kim, I Piris, A Gabree, M Taylor, M Lane, AM DeAngelis, MM Gragoudas, E Duncan, LM Tsao, H AF Njauw, Ching-Ni Jenny Kim, Ivana Piris, Adriano Gabree, Michele Taylor, Michael Lane, Anne Marie DeAngelis, Margaret M. Gragoudas, Evangelos Duncan, Lyn M. Tsao, Hensin TI Germline BAP1 Inactivation Is Preferentially Associated with Metastatic Ocular Melanoma and Cutaneous-Ocular Melanoma Families SO PLOS ONE LA English DT Article ID CDKN2A CARRIER PROBABILITY; UVEAL MELANOMA; MUTATIONS; MESOTHELIOMA; PREDISPOSE; MENINGIOMA; MODEL AB Background: BAP1 has been shown to be a target of both somatic alteration in high-risk ocular melanomas (OM) and germline inactivation in a few individuals from cancer-prone families. These findings suggest that constitutional BAP1 changes may predispose individuals to metastatic OM and that familial permeation of deleterious alleles could delineate a new cancer syndrome. Design: To characterize BAP1's contribution to melanoma risk, we sequenced BAP1 in a set of 100 patients with OM, including 50 metastatic OM cases and 50 matched non-metastatic OM controls, and 200 individuals with cutaneous melanoma (CM) including 7 CM patients from CM-OM families and 193 CM patients from CM-non-OM kindreds. Results: Germline BAP1 mutations were detected in 4/50 patients with metastatic OM and 0/50 cases of non-metastatic OM (8% vs. 0%, p = 0.059). Since 2/4 of the BAP1 carriers reported a family history of CM, we analyzed 200 additional hereditary CM patients and found mutations in 2/7 CM probands from CM-OM families and 1/193 probands from CM-non-OM kindreds (29% vs. 0.52%, p = .003). Germline mutations co-segregated with both CM and OM phenotypes and were associated with the presence of unique nevoid melanomas and highly atypical nevoid melanoma-like melanocytic proliferations (NEMMPs). Interestingly, 7/14 germline variants identified to date reside in C-terminus suggesting that the BRCA1 binding domain is important in cancer predisposition. Conclusion: Germline BAP1 mutations are associated with a more aggressive OM phenotype and a recurrent phenotypic complex of cutaneous/ocular melanoma, atypical melanocytic proliferations and other internal neoplasms (ie. COMMON syndrome), which could be a useful clinical marker for constitutive BAP1 inactivation. C1 [Njauw, Ching-Ni Jenny; Taylor, Michael; Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kim, Ivana; Lane, Anne Marie; Gragoudas, Evangelos] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. [Piris, Adriano; Duncan, Lyn M.] Massachusetts Gen Hosp, Dept Pathol, Div Dermatopathol, Boston, MA 02114 USA. [Gabree, Michele; Tsao, Hensin] Massachusetts Gen Hosp, Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA. [DeAngelis, Margaret M.] Univ Utah, Sch Med, John A Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA. [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Njauw, CNJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM htsao@partners.org RI Njauw, Ching-Ni/H-8046-2012; DeAngelis, e/J-7863-2015 FU National Institutes of Health [K24 CA14920, P50 CA93683]; American Skin Association; American Cancer Society FX The study was supported in part by the National Institutes of Health (K24 CA14920 and P50 CA93683), the American Skin Association, the American Cancer Society, and the generous philanthropic donors to the MGH Millennium Melanoma Fund and the MEEI Melanoma Research Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 16 TC 93 Z9 93 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 24 PY 2012 VL 7 IS 4 AR e35295 DI 10.1371/journal.pone.0035295 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959VE UT WOS:000305343200023 PM 22545102 ER PT J AU Scherzer, R Estrella, M Li, YM Choi, AI Deeks, SG Grunfeld, C Shlipak, MG AF Scherzer, Rebecca Estrella, Michelle Li, Yongmei Choi, Andy I. Deeks, Steven G. Grunfeld, Carl Shlipak, Michael G. TI Association of tenofovir exposure with kidney disease risk in HIV infection SO AIDS LA English DT Article DE antiretroviral therapy; HIV; kidney disease; tenofovir ID ANTIRETROVIRAL-NAIVE PATIENTS; MARGINAL STRUCTURAL MODELS; TUBULAR DYSFUNCTION; DISOPROXIL FUMARATE; FANCONI-SYNDROME; RENAL TOXICITY; DIABETES-INSIPIDUS; RANDOMIZED-TRIAL; THERAPY; ADHERENCE AB Objective: Despite widespread HAART use, HIV disease remains associated with increased risk of kidney disease. Whether tenofovir use is associated with higher risk of kidney disease is controversial. Design: We evaluated the association of cumulative and ever exposure to tenofovir on kidney outcomes in 10 841 HIV-infected patients from the Veterans Health Administration who initiated antiretroviral therapy from 1997 to 2007. Methods: Cox proportional hazards and marginal structural models evaluated associations between tenofovir and time to first occurrence of proteinuria (two consecutive urine dipstick measurements >= 30 mg/dl), rapid decline in kidney function (>= 3 ml/min per 1.73 m(2) annual decline), and chronic kidney disease (CKD; estimated glomerular filtration rate <60 ml/min per 1.73 m(2)). Results: Median follow-up ranged from 3.9 years (proteinuria) to 5.5 years (CKD), during which 3400 proteinuria, 3078 rapid decline, and 533 CKD events occurred. After multivariable adjustment, each year of exposure to tenofovir was associated with 34% increased risk of proteinuria [95% confidence interval (CI) 25-45, P < 0.0001], 11% increased risk of rapid decline (3-18, P = 0.0033), and 33% increased risk of CKD (18-51, P < 0.0001). Preexisting renal risk factors did not appear to worsen the effects of tenofovir. Other antiretroviral drugs showed weaker or inconsistent associations with kidney disease events. Among those who discontinued tenofovir use, risk of kidney disease events did not appear to decrease during follow-up. Conclusion: Tenofovir exposure was independently associated with increased risk for three types of kidney disease events, and did not appear to be reversible. Because subtle kidney function decline affects long-term morbidity and mortality, the balance between efficacy and probable adverse effects requires further study. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Scherzer, Rebecca; Li, Yongmei; Choi, Andy I.; Grunfeld, Carl; Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Scherzer, Rebecca; Li, Yongmei; Choi, Andy I.; Grunfeld, Carl; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Estrella, Michelle] Johns Hopkins Sch Med, Baltimore, MD USA. [Deeks, Steven G.] San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA 94110 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, Dept Med, Box 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU National Institutes of Health [K23DK080645-1A1, 1R03AG034871-01, K24AI069994, R01 DK066488-01, K23DK081317]; National Center for Research Resources [KL2 RR024130]; American Heart Association; Veterans Affairs Public Health Strategic Healthcare Group; Merck; Bristol-Myers Squibb; Gilead; Roche Molecular Sciences; Abbott; Gilead Sciences; EMD Serono; Theratechnologies FX This study was supported by the National Institutes of Health [K23DK080645-1A1 (A.I.C.), 1R03AG034871-01 (A.I.C./M.G.S.), K24AI069994, R01 DK066488-01 (M.G.S./A.I.C.), K23DK081317 (M.E.)], the National Center for Research Resources (KL2 RR024130), the American Heart Association Established Investigator Award (MGS), and the Veterans Affairs Public Health Strategic Healthcare Group, which were administered by the Northern California Institute for Research and Education, and with resources of the Veterans Affairs Medical Center, San Francisco, California. These funding sources had no involvement in the design or execution of this study. S.G.D. receives research support from Merck, Bristol-Myers Squibb, Gilead, and Roche Molecular Sciences. C. G. has received prior research funding and/or honorarium from Merck, Bristol-Myers Squibb, Abbott, Gilead Sciences, EMD Serono and Theratechnologies. NR 38 TC 156 Z9 161 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 24 PY 2012 VL 26 IS 7 BP 867 EP 875 DI 10.1097/QAD.0b013e328351f68f PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 926EB UT WOS:000302813000012 PM 22313955 ER PT J AU van der Straten, A Van Damme, L Haberer, JE Bangsberg, DR AF van der Straten, Ariane Van Damme, Lut Haberer, Jessica E. Bangsberg, David R. TI Unraveling the divergent results of pre-exposure prophylaxis trials for HIV prevention SO AIDS LA English DT Article DE antiretrovirals; biomedical HIV prevention trials; microbicide; pre-exposure prophylaxis ID TENOFOVIR DISOPROXIL FUMARATE; SIMPLEX-VIRUS TYPE-2; HORMONAL CONTRACEPTIVES; ANTIRETROVIRAL THERAPY; IN-VITRO; INFECTION; WOMEN; PHARMACOKINETICS; TRANSMISSION; MICROBICIDE AB Although the balance of recent evidence supports the efficacy of antiretroviral (ARV)based pre-exposure prophylaxis (PrEP) against HIV-1 infection, recent negative trial results are perplexing. Of seven trials with available HIV endpoints, three different products have been tested: tenofovir 1% vaginal gel, oral tenofovir disoproxil fumarate (TDF) tablets, and TDF/emtricitabine tablets. Six of these trials were conducted exclusively in sub-Saharan Africa; all found the products to be well tolerated, and four demonstrated effectiveness. Furthermore, the HIV Prevention Trial Network (HPTN) 052 trial recently confirmed that antiretroviral treatment leads to 96% reduction in transmission to HIV-negative partners in HIV-serodiscordant couples. These results, along with human and animal data, provide substantial evidence for the efficacy of antiretroviral-based HIV prevention. Yet assessment of oral TDF/emtricitabine in the FEM-PrEP study and of oral and vaginal tenofovir in the Microbicide Trial Network (MTN)-003 trial (VOICE) was stopped for futility. How do we make sense of these discrepant results? We believe that adherence is a key factor, although it cannot be the only factor. Expanding upon a recent editorial in the Lancet, we discuss the impact of suboptimal product adherence on PrEP efficacy in the context of variable drug concentration at the exposure site, integrity of the vaginal epithelium, and the role of acute infection. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [van der Straten, Ariane] RTI Int, Womens Global Hlth Imperat, San Francisco, CA 94104 USA. [van der Straten, Ariane] Univ Calif San Francisco, Dept Med, Ctr AIDS Prevent Studies, San Francisco, CA USA. [Van Damme, Lut] FHI 360, Arlington, VA USA. [Haberer, Jessica E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Haberer, Jessica E.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Haberer, Jessica E.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David R.] Ragon Inst MGH MIT & Harvard Univ, Boston, MA USA. RP van der Straten, A (reprint author), RTI Int, Womens Global Hlth Imperat, 114 Sansome St,Suite 500, San Francisco, CA 94104 USA. EM ariane@rti.org FU USAID; Bill and Melinda Gates Foundation; [K-23 087228]; [K-24 MH87227] FX Support for preparation of this manuscript was provided by a Professional Development Award from RTI International for A.S.L.V.D. was supported by USAID funding. J.E.H. and D.R.B. were supported by the Bill and Melinda Gates Foundation. J.E.H. was supported by K-23 087228 and D.R.B. was supported by K-24 MH87227 NR 49 TC 169 Z9 171 U1 5 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD APR 24 PY 2012 VL 26 IS 7 BP F13 EP F19 DI 10.1097/QAD.0b013e3283522272 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 926EB UT WOS:000302813000001 PM 22333749 ER PT J AU Fernandez-Rebollo, E Maeda, A Reyes, M Turan, S Frohlich, LF Plagge, A Kelsey, G Juppner, H Bastepe, M AF Fernandez-Rebollo, Eduardo Maeda, Akira Reyes, Monica Turan, Serap Froehlich, Leopold F. Plagge, Antonius Kelsey, Gavin Jueppner, Harald Bastepe, Murat TI Loss of XL alpha s (extra-large alpha s) imprinting results in early postnatal hypoglycemia and lethality in a mouse model of pseudohypoparathyroidism Ib SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE stimulatory G protein; renal proximal tubule; cyclic AMP ID GNAS LOCUS; G-PROTEIN; GS-ALPHA; AUTOSOMAL-DOMINANT; CHROMOSOME 2; ANTISENSE TRANSCRIPT; SUBUNIT G(S)ALPHA; CONTROL ELEMENT; GENE; METHYLATION AB Maternal deletion of the NESP55 differentially methylated region (DMR) (delNESP55/ASdel3-4(m), delNAS(m)) from the GNAS locus in humans causes autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib(delNASm)), a disorder of proximal tubular parathyroid hormone (PTH) resistance associated with loss of maternal GNAS methylation imprints. Mice carrying a similar, maternally inherited deletion of the Nesp55 DMR (Delta Nesp55(m)) replicate these Gnas epigenetic abnormalities and show evidence for PTH resistance, yet these mice demonstrate 100% mortality during the early postnatal period. We investigated whether the loss of extralarge as (XL alpha s) imprinting and the resultant biallelic expression of XLas are responsible for the early postnatal lethality in Delta Nesp55(m) mice. First, we found that Delta Nesp55(m) mice are hypoglycemic and have reduced stomach-to-body weight ratio. We then generated mice having the same epigenetic abnormalities as the Delta Nesp55(m) mice but with normalized XLas expression due to the paternal disruption of the exon giving rise to this Gnas product. These mice (Delta Nesp55(m)/Gnasxl(m+/p-)) showed nearly 100% survival up to postnatal day 10, and a substantial number of them lived to adulthood. The hypoglycemia and reduced stomach-to-body weight ratio observed in 2-d-old Delta Nesp55(m) mice were rescued in the Delta Nesp55(m)/Gnasxl(m+/p-) mice. Surviving double-mutant animals had significantly reduced Gas mRNA levels and showed hypocalcemia, hyperphosphatemia, and elevated PTH levels, thus providing a viable model of human AD-PHP-Ib. Our findings show that the hypoglycemia and early postnatal lethality caused by the maternal deletion of the Nesp55 DMR result from biallelic XLas expression. The double-mutant mice will help elucidate the pathophysiological mechanisms underlying AD-PHP-Ib. C1 [Fernandez-Rebollo, Eduardo; Maeda, Akira; Reyes, Monica; Turan, Serap; Froehlich, Leopold F.; Jueppner, Harald; Bastepe, Murat] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Turan, Serap] Marmara Univ, Sch Med, TR-34899 Istanbul, Turkey. [Froehlich, Leopold F.] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria. [Plagge, Antonius] Univ Liverpool, Inst Translat Med, Liverpool L69 3BX, Merseyside, England. [Kelsey, Gavin] Babraham Inst, Epigenet Programme, Cambridge CB22 3AT, England. [Kelsey, Gavin] Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 1TN, England. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu OI FERNANDEZ-REBOLLO, EDUARDO/0000-0002-4378-7590 FU National Institutes of Health [R01DK073911, R37DK46718-16]; UK Medical Research Council; Royal Society; Biotechnology and Biological Sciences Research Council; European Society; Lilly USA, LLC FX We thank Drs. Joseph Majzoub and Rong Zhang for help with the corticosterone measurements and Dr. Henry Kronenberg for critically reviewing the manuscript. This work was supported by National Institutes of Health Grants R01DK073911 (to M. B.) and R37DK46718-16 (to H.J.). Work in the A.P. laboratory is supported by the UK Medical Research Council and the Royal Society. Work in the G.K. laboratory is supported by UK Medical Research Council and the Biotechnology and Biological Sciences Research Council. S.T. was supported by a Sabbatical Leave Programme grant from the European Society for Paediatric Endocrinology through an educational grant from Lilly USA, LLC. NR 56 TC 13 Z9 14 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2012 VL 109 IS 17 BP 6638 EP 6643 DI 10.1073/pnas.1117608109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 931WD UT WOS:000303249100061 PM 22496590 ER PT J AU Demichelis, F Setlur, SR Banerjee, S Chakravarty, D Chen, JYH Chen, CX Huang, JL Beltran, H Oldridge, DA Kitabayashi, N Stenzel, B Schaefer, G Horninger, W Bektic, J Chinnaiyan, AM Goldenberg, S Siddiqui, J Regan, MM Kearney, M Soong, TD Rickman, DS Elemento, O Wei, JT Scherr, DS Sanda, MA Bartsch, G Lee, C Klocker, H Rubin, MA AF Demichelis, Francesca Setlur, Sunita R. Banerjee, Samprit Chakravarty, Dimple Chen, Jin Yun Helen Chen, Chen X. Huang, Julie Beltran, Himisha Oldridge, Derek A. Kitabayashi, Naoki Stenzel, Birgit Schaefer, Georg Horninger, Wolfgang Bektic, Jasmin Chinnaiyan, Arul M. Goldenberg, Sagit Siddiqui, Javed Regan, Meredith M. Kearney, Michale Soong, T. David Rickman, David S. Elemento, Olivier Wei, John T. Scherr, Douglas S. Sanda, Martin A. Bartsch, Georg Lee, Charles Klocker, Helmut Rubin, Mark A. TI Identification of functionally active, low frequency copy number variants at 15q21.3 and 12q21.31 associated with prostate cancer risk SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer genetics; functionally active DNA loci; cancer predisposition; metabolism; chromosome looping ID GENOME-WIDE ASSOCIATION; STRUCTURAL VARIATION; MORTALITY; DISEASE; EXPRESSION; GENE; TUMORIGENESIS; POLYMORPHISM; ELEMENTS; DISTINCT AB Copy number variants (CNVs) are a recently recognized class of human germ line polymorphisms and are associated with a variety of human diseases, including cancer. Because of the strong genetic influence on prostate cancer, we sought to identify functionally active CNVs associated with susceptibility of this cancer type. We queried low-frequency biallelic CNVs from 1,903 men of Caucasian origin enrolled in the Tyrol Prostate Specific Antigen Screening Cohort and discovered two CNVs strongly associated with prostate cancer risk. The first risk locus (P = 7.7 x 10(-4), odds ratio = 2.78) maps to 15q21.3 and overlaps a noncoding enhancer element that contains multiple activator protein 1 (AP-1) transcription factor binding sites. Chromosome conformation capture (Hi-C) data suggested direct cis-interactions with distant genes. The second risk locus (P = 2.6 x 10(-3), odds ratio = 4.8) maps to the alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C (MGAT4C) gene on 12q21.31. In vitro cell-line assays found this gene to significantly modulate cell proliferation and migration in both benign and cancer prostate cells. Furthermore, MGAT4C was significantly overexpressed in metastatic versus localized prostate cancer. These two risk associations were replicated in an independent PSA-screened cohort of 800men (15q21.3, combined P = 0.006; 12q21.31, combined P = 0.026). These findings establish noncoding and coding germ line CNVs as significant risk factors for prostate cancer susceptibility and implicate their role in disease development and progression. C1 [Demichelis, Francesca; Chakravarty, Dimple; Chen, Chen X.; Huang, Julie; Oldridge, Derek A.; Kitabayashi, Naoki; Rickman, David S.; Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Banerjee, Samprit] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10065 USA. [Goldenberg, Sagit; Scherr, Douglas S.; Rubin, Mark A.] Weill Cornell Med Coll, Dept Urol, New York, NY 10065 USA. [Beltran, Himisha] Weill Cornell Med Coll, Div Hematol & Med Oncol, New York, NY 10065 USA. [Demichelis, Francesca; Soong, T. David; Elemento, Olivier] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10065 USA. [Demichelis, Francesca] Univ Trent, Ctr Integrat Biol, I-38122 Trento, Italy. [Setlur, Sunita R.; Chen, Jin Yun Helen; Lee, Charles] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Setlur, Sunita R.; Chen, Jin Yun Helen; Lee, Charles] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Stenzel, Birgit; Schaefer, Georg; Horninger, Wolfgang; Bektic, Jasmin; Bartsch, Georg; Klocker, Helmut] Innsbruck Med Univ, Dept Urol, A-6020 Innsbruck, Austria. [Siddiqui, Javed; Wei, John T.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. [Chinnaiyan, Arul M.; Siddiqui, Javed] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. [Regan, Meredith M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kearney, Michale; Sanda, Martin A.] Beth Israel Deaconess Med Ctr, Dept Urol, Boston, MA 02115 USA. RP Demichelis, F (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. EM demichelis@science.unitn.it; rubinma@med.cornell.edu RI Sanda, Martin/A-6202-2013; Chakravarty, Dimple/N-3325-2014; Sanda, Martin/B-2023-2015; Wei, John/E-8967-2012; OI Chakravarty, Dimple/0000-0002-8588-8461; Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 FU Early Detection Research Network National Cancer Institute [UO1CA113913, U01CA11275]; Starr Cancer Consortium [NCI-CA-R01-116337]; Clinical and Translational Science Center; Department of Defense [PC094516]; National Human Genome Research Institute [P41HG004221, UO1HG005209] FX We thank R. Kim for the Weill Cornell Institutional Biobank; W. M. Hussain, A. Romanel, and R. R. Hossain for technical support; H. Hauffe, C. Seifarth, and E. Steiner for organizing the clinical data; D. Govindaraju for his insightful comments on epistatic interactions; and the 1000 Genome Project, the International HapMap Consortium, and the Encyclopedia of DNA Elements (ENCODE) Project (locus-specific information). This work was supported in part by Early Detection Research Network National Cancer Institute Grants UO1CA113913 (to M.A.S., J.T.W., D.S.S., and M.A.R.) and U01CA11275 (to F.D., A.M.C., and M.A.R.); the Starr Cancer Consortium (F.D., S.R.S., S.B., C.L., and M.A.R.); Grant NCI-CA-R01-116337 (to F.D., S.B., and M.A.R.); the Clinical and Translational Science Center (F.D.); Department of Defense Grant PC094516 (to F.D.); and National Human Genome Research Institute Grants P41HG004221 and UO1HG005209 (to C.L.). NR 48 TC 15 Z9 15 U1 2 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2012 VL 109 IS 17 BP 6686 EP 6691 DI 10.1073/pnas.1117405109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 931WD UT WOS:000303249100069 PM 22496589 ER PT J AU Yoon, JH Di Vito, L Moses, J Fearon, W Yeung, A Zhang, SS Bezerra, H Costa, M Jang, IK AF Yoon, Joo Heung Di Vito, Luca Moses, Jeffery Fearon, William Yeung, Alan Zhang, Shaosong Bezerra, Hiram Costa, Marco Jang, Ik-Kyung TI Feasibility and Safety of the Second Generation, Frequency Domain Optical Coherence Tomography: A Multi-Center Study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 17th Annual Interventional Vascular Therapeutics Angioplasty Summit-Transcatheter Cardiovascular Therapeutics Asia Pacific Symposium CY APR 24-27, 2012 CL Seoul, SOUTH KOREA C1 [Yoon, Joo Heung; Di Vito, Luca; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Moses, Jeffery] Columbia Univ, Med Ctr, New York, NY USA. [Moses, Jeffery] Cardiovasc Res Fdn, New York, NY USA. [Fearon, William; Yeung, Alan] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Zhang, Shaosong] Light Lab Imaging St Jude Med, Westford, MA USA. [Bezerra, Hiram; Costa, Marco] Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 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 APR 24 PY 2012 VL 109 IS 7 SU S BP 121S EP 122S PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916NZ UT WOS:000302111800248 ER PT J AU Singer, DE Go, AS AF Singer, Daniel E. Go, Alan S. TI A New Era in Stroke Prevention for Atrial Fibrillation SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID WARFARIN; ANTICOAGULATION; DABIGATRAN; THERAPY C1 [Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. RP Singer, DE (reprint author), Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. EM dsinger@partners.org NR 11 TC 1 Z9 2 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 23 PY 2012 VL 172 IS 8 BP 631 EP 633 DI 10.1001/archinternmed.2012.897 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 930HQ UT WOS:000303128700006 PM 23446882 ER PT J AU Matlock, DD Peterson, PN Wang, YF Curtis, JP Reynolds, MR Varosy, PD Masoudi, FA AF Matlock, Dan D. Peterson, Pamela N. Wang, Yongfei Curtis, Jeptha P. Reynolds, Matthew R. Varosy, Paul D. Masoudi, Frederick A. TI Variation in Use of Dual-Chamber Implantable Cardioverter-Defibrillators Results From the National Cardiovascular Data Registry SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID LIFE TREATMENT INTENSITY; HEALTH-CARE; REGIONAL-VARIATIONS; HOSPITAL VARIATION; ADVERSE EVENTS; HEART-FAILURE; UNITED-STATES; TRIAL; COST; PERCEPTIONS AB Background: Among patients without an indication for a pacemaker, current evidence is inconclusive whether a dual-chamber implantable cardioverter-defibrillator (ICD) is superior to a single-chamber ICD. The current use of dual-chamber ICDs is not well characterized. Methods: We conducted a cross-sectional study exploring hospital-level variation in the use of dual-chamber ICDs across the United States. Patients receiving a primary prevention ICD from 2006 through 2009 without a documented indication for a pacemaker were included. Multivariate hierarchical logistic regression was used to explore patient, health care provider, and physician factors related to the use of a dual-chamber device. Results: Dual-chamber devices were implanted in 58% of the 87 115 patients without a pacing indication among 1293 hospitals, with hospital rates ranging from 0% in 33 centers to 100% in 109 centers. In multivariate analysis, geographic region was a strong independent predictor of dual-chamber device use, ranging from 36.4% in New England (reference region) to 66.4% in the Pacific region (odds ratio [OR], 5.25; 95% CI, 3.35-8.21). Hospital clustering was assessed using a median OR which was 3.96, meaning that 2 identical patients at different hospitals would have nearly a 4-fold difference in their chance of receiving a dual-chamber ICD. Conclusions: Use of dual-chamber ICDs for the primary prevention of sudden cardiac death among patients without an indication for permanent pacing varies markedly at the hospital level in the United States. This is a clear example of how practice can vary independent of patient factors. Arch Intern Med. 2012;172(8):634-641 C1 [Matlock, Dan D.] Univ Colorado Denver, Sch Med, Div Gen Internal Med, Acad Off 1,Dept Med, Aurora, CO 80045 USA. [Matlock, Dan D.; Peterson, Pamela N.; Varosy, Paul D.; Masoudi, Frederick A.] Colorado Cardiovasc Outcomes Res Grp, Denver, CO USA. [Matlock, Dan D.; Peterson, Pamela N.; Masoudi, Frederick A.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Peterson, Pamela N.] Denver Hlth Med Ctr, Dept Med, Denver, CO USA. [Wang, Yongfei; Curtis, Jeptha P.] Yale Univ, Dept Internal Med, New Haven, CT USA. [Reynolds, Matthew R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiol, Boston, MA 02215 USA. [Reynolds, Matthew R.] Boston VA Healthcare Syst, Boston, MA USA. [Varosy, Paul D.] Vet Affairs Eastern Colorado Hlth Care Syst, Med Serv, Cardiol Sect, Denver, CO USA. RP Matlock, DD (reprint author), Univ Colorado Denver, Sch Med, Div Gen Internal Med, Acad Off 1,Dept Med, 12631 E 17th Ave,Campus Box B-180, Aurora, CO 80045 USA. EM daniel.matlock@ucdenver.edu FU American College of Cardiology (ACC); Medtronic; ACC Foundation; Oklahoma Foundation for Medical Quality; Agency for Healthcare Research and Quality; National Heart, Lung, and Blood Institute; Heart Rhythm Society; National Institute on Aging [AG040696-01]; California Health Care Foundation; Parsemus Foundation FX Financial Disclosure: Dr Curtis has received salary support under contract with the American College of Cardiology (ACC) to provide data analytic services for the ICD registry and has significant stock holdings in Medtronic, a maker of ICDs. Dr Reynolds has received consulting fees from Medtronic. Dr Masoudi has had contracts with and has received grants from the ACC Foundation and the Oklahoma Foundation for Medical Quality; and has received grants from the Agency for Healthcare Research and Quality the National Heart, Lung, and Blood Institute, and the Heart Rhythm Society.; Funding/Support: Dr Matlock was supported as a Hartford Geriatrics Health Outcomes Research Scholar and by K23 funding (AG040696-01) from the National Institute on Aging.; Funding for Less Is More: Staff support for topics research funded by grants from the California Health Care Foundation and the Parsemus Foundation. NR 42 TC 19 Z9 19 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 23 PY 2012 VL 172 IS 8 BP 634 EP 641 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 930HQ UT WOS:000303128700007 PM 22529229 ER PT J AU Wong, SPY Kreuter, W O'Hare, AM AF Wong, Susan P. Y. Kreuter, William O'Hare, Ann M. TI Treatment Intensity at the End of Life in Older Adults Receiving Long-term Dialysis SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID STAGE RENAL-DISEASE; HEART-FAILURE; CARE C1 [Wong, Susan P. Y.; O'Hare, Ann M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Kreuter, William] Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. [O'Hare, Ann M.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. RP Wong, SPY (reprint author), Univ Washington, Dept Med, 1959 Pacific St NE,POB 359945, Seattle, WA 98195 USA. EM spywong@uw.edu FU NIA NIH HHS [5K23AG028980] NR 9 TC 61 Z9 61 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 23 PY 2012 VL 172 IS 8 BP 661 EP 663 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 930HQ UT WOS:000303128700015 PM 22529233 ER PT J AU Cowan, RE Fregly, BJ Boninger, ML Chan, L Rodgers, MM Reinkensmeyer, DJ AF Cowan, Rachel E. Fregly, Benjamin J. Boninger, Michael L. Chan, Leighton Rodgers, Mary M. Reinkensmeyer, David J. TI Recent trends in assistive technology for mobility SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Review DE Disability; Assistive technology; Robotics ID ANKLE-FOOT ORTHOSIS; SYSTEM; PROSTHETICS; WHEELCHAIR; VISION; DESIGN; INJURY; GAIT AB Loss of physical mobility makes maximal participation in desired activities more difficult and in the worst case fully prevents participation. This paper surveys recent work in assistive technology to improve mobility for persons with a disability, drawing on examples observed during a tour of academic and industrial research sites in Europe. The underlying theme of this recent work is a more seamless integration of the capabilities of the user and the assistive technology. This improved integration spans diverse technologies, including powered wheelchairs, prosthetic limbs, functional electrical stimulation, and wearable exoskeletons. Improved integration is being accomplished in three ways: 1) improving the assistive technology mechanics; 2) improving the user-technology physical interface; and 3) sharing of control between the user and the technology. We provide an overview of these improvements in user-technology integration and discuss whether such improvements have the potential to be transformative for people with mobility impairments. C1 [Cowan, Rachel E.] Univ Miami, Miller Sch Med, Dept Neurol Surg, Miami Project Cure Paralysis, Miami, FL 33136 USA. [Fregly, Benjamin J.] Univ Florida, Dept Mech & Aerosp Engn, Gainesville, FL 32611 USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Sch Med, Pittsburgh, PA 15260 USA. [Chan, Leighton] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Rodgers, Mary M.] Univ Maryland, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 21201 USA. [Rodgers, Mary M.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. [Reinkensmeyer, David J.] Univ Calif Irvine, Dept Mech & Aerosp Engn, Dept Anat & Neurobiol, Dept Biomed Engn, Irvine, CA 92697 USA. [Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. RP Cowan, RE (reprint author), Univ Miami, Miller Sch Med, Dept Neurol Surg, Miami Project Cure Paralysis, 1095 NW 14th Terrace, Miami, FL 33136 USA. EM rcowan@med.miami.edu RI Fregly, Benjamin/O-6860-2016; OI Fregly, Benjamin/0000-0003-1166-4358; Boninger, Michael/0000-0001-6966-919X NR 31 TC 25 Z9 25 U1 6 U2 57 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD APR 20 PY 2012 VL 9 AR 20 DI 10.1186/1743-0003-9-20 PG 8 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA 981ZY UT WOS:000307012700001 PM 22520500 ER PT J AU Lovly, CM Dahlman, KB Fohn, LE Su, ZL Dias-Santagata, D Hicks, DJ Hucks, D Berry, E Terry, C Duke, M Su, YJ Sobolik-Delmaire, T Richmond, A Kelley, MC Vnencak-Jones, CL Iafrate, AJ Sosman, J Pao, W AF Lovly, Christine M. Dahlman, Kimberly Brown Fohn, Laurel E. Su, Zengliu Dias-Santagata, Dora Hicks, Donna J. Hucks, Donald Berry, Elizabeth Terry, Charles Duke, MarKeesa Su, Yingjun Sobolik-Delmaire, Tammy Richmond, Ann Kelley, Mark C. Vnencak-Jones, Cindy L. Iafrate, A. John Sosman, Jeffrey Pao, William TI Routine Multiplex Mutational Profiling of Melanomas Enables Enrollment in Genotype-Driven Therapeutic Trials SO PLOS ONE LA English DT Article ID METASTATIC MALIGNANT-MELANOMA; COOPERATIVE-ONCOLOGY-GROUP; PHASE-III TRIAL; UVEAL MELANOMA; BRAF MUTATIONS; BETA-CATENIN; TUMOR PROGRESSION; EXON-3 MUTATIONS; KIT MUTATION; COPY NUMBER AB Purpose: Knowledge of tumor mutation status is becoming increasingly important for the treatment of cancer, as mutation-specific inhibitors are being developed for clinical use that target only sub-populations of patients with particular tumor genotypes. Melanoma provides a recent example of this paradigm. We report here development, validation, and implementation of an assay designed to simultaneously detect 43 common somatic point mutations in 6 genes (BRAF, NRAS, KIT, GNAQ, GNA11, and CTNNB1) potentially relevant to existing and emerging targeted therapies specifically in melanoma. Methods: The test utilizes the SNaPshot method (multiplex PCR, multiplex primer extension, and capillary electrophoresis) and can be performed rapidly with high sensitivity (requiring 5-10% mutant allele frequency) and minimal amounts of DNA (10-20 nanograms). The assay was validated using cell lines, fresh-frozen tissue, and formalin-fixed paraffin embedded tissue. Clinical characteristics and the impact on clinical trial enrollment were then assessed for the first 150 melanoma patients whose tumors were genotyped in the Vanderbilt molecular diagnostics lab. Results: Directing this test to a single disease, 90 of 150 (60%) melanomas from sites throughout the body harbored a mutation tested, including 57, 23, 6, 3, and 2 mutations in BRAF, NRAS, GNAQ, KIT, and CTNNB1, respectively. Among BRAF V600 mutations, 79%, 12%, 5%, and 4% were V600E, V600K, V600R, and V600M, respectively. 23 of 54 (43%) patients with mutation harboring metastatic disease were subsequently enrolled in genotype-driven trials. Conclusion: We present development of a simple mutational profiling screen for clinically relevant mutations in melanoma. Adoption of this genetically-informed approach to the treatment of melanoma has already had an impact on clinical trial enrollment and prioritization of therapy for patients with the disease. C1 [Lovly, Christine M.; Fohn, Laurel E.; Su, Zengliu; Berry, Elizabeth; Terry, Charles; Duke, MarKeesa; Sosman, Jeffrey; Pao, William] Vanderbilt Univ, Sch Med, Div Hematol Oncol, Dept Med,Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Dahlman, Kimberly Brown; Su, Yingjun; Sobolik-Delmaire, Tammy] Vanderbilt Univ, Sch Med, Dept Canc Biol, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Dias-Santagata, Dora; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Translat Res Lab, Boston, MA 02114 USA. [Dias-Santagata, Dora; Iafrate, A. John] Harvard Univ, Sch Med, Boston, MA USA. [Hicks, Donna J.; Hucks, Donald] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Med Ctr, Nashville, TN 37212 USA. [Richmond, Ann] Vanderbilt Univ, Sch Med, Dept Canc Biol, Dept Vet Affairs,Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Kelley, Mark C.] Vanderbilt Univ, Sch Med, Div Surg Oncol, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Vnencak-Jones, Cindy L.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37212 USA. [Vnencak-Jones, Cindy L.] Vanderbilt Univ, Med Ctr, Dept Microbiol, Nashville, TN 37212 USA. [Vnencak-Jones, Cindy L.] Vanderbilt Univ, Med Ctr, Dept Immunol & Pediat, Nashville, TN 37212 USA. RP Pao, W (reprint author), Vanderbilt Univ, Sch Med, Div Hematol Oncol, Dept Med,Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. EM william.pao@vanderbilt.edu RI Richmond, Ann/A-3048-2014 FU VICC Cancer Center [CA68485]; TJ Martell Foundation; Kleberg Foundation; National Institutes of Health / National Cancer Institute [5K24 CA97588-06]; American Cancer Society; Department of Veterans Affairs; Valvano Foundation; Vanderbilt Institute for Clinical and Translational Research (VICTR) CTSA [UL1 RR024975-01]; AstraZeneca FX This work was supported by a VICC Cancer Center Core Grant (CA68485), the TJ Martell Foundation, the Kleberg Foundation, the National Institutes of Health / National Cancer Institute 5K24 CA97588-06 (JS), the American Cancer Society (Mary Hendrickson-Johnson Melanoma Professorship to JS), the Department of Veterans Affairs (Senior Research Career Scientist Award to AR), the Valvano Foundation (to JS and AR), the Vanderbilt Institute for Clinical and Translational Research (VICTR) CTSA grant (UL1 RR024975-01), and an anonymous donor. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Please note: WP has done consulting for Bristol-Myers Squibb and has received research funding from AstraZeneca. However, this is NOT related to the current study. NR 56 TC 81 Z9 83 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 20 PY 2012 VL 7 IS 4 AR e35309 DI 10.1371/journal.pone.0035309 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UD UT WOS:000305339200052 PM 22536370 ER PT J AU Reinkensmeyer, DJ Bonato, P Boninger, ML Chan, L Cowan, RE Fregly, BJ Rodgers, MM AF Reinkensmeyer, David J. Bonato, Paolo Boninger, Michael L. Chan, Leighton Cowan, Rachel E. Fregly, Benjamin J. Rodgers, Mary M. TI Major trends in mobility technology research and development: Overview of the results of the NSF-WTEC European study SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Editorial Material AB Mobility technologies, including wheelchairs, prostheses, joint replacements, assistive devices, and therapeutic exercise equipment help millions of people participate in desired life activities. Yet, these technologies are not yet fully transformative because many desired activities cannot be pursued or are difficult to pursue for the millions of individuals with mobility related impairments. This WTEC study, initiated and funded by the National Science Foundation, was designed to gather information on European innovations and trends in technology that might lead to greater mobility for a wider range of people. What might these transformative technologies be and how might they arise? Based on visits to leading mobility technology research labs in western Europe, the WTEC panel identified eight major trends in mobility technology research. This commentary summarizes these trends, which are then described in detail in companion papers appearing in this special issue. C1 [Reinkensmeyer, David J.] Univ Calif Irvine, Dept Biomed Engn, Dept Anat & Neurobiol, Dept Mech & Aerosp Engn, Irvine, CA 92697 USA. [Bonato, Paolo] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept PM&R, Boston, MA 02114 USA. [Boninger, Michael L.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. [Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. [Chan, Leighton] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Cowan, Rachel E.] Univ Miami, Miller Sch Med, Dept Neurol Surg, Miami Project Cure Paralysis, Miami, FL 33136 USA. [Fregly, Benjamin J.] Univ Florida, Dept Mech & Aerosp Engn, Gainesville, FL 32611 USA. [Rodgers, Mary M.] Univ Maryland, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 21201 USA. [Rodgers, Mary M.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Reinkensmeyer, DJ (reprint author), Univ Calif Irvine, Dept Biomed Engn, Dept Anat & Neurobiol, Dept Mech & Aerosp Engn, 4200 Engn Gateway, Irvine, CA 92697 USA. EM dreinken@uci.edu RI Fregly, Benjamin/O-6860-2016; OI Fregly, Benjamin/0000-0003-1166-4358; Boninger, Michael/0000-0001-6966-919X NR 0 TC 10 Z9 10 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD APR 20 PY 2012 VL 9 AR 22 DI 10.1186/1743-0003-9-22 PG 4 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA 940AO UT WOS:000303862600001 PM 22520596 ER PT J AU Faris, JE Ryan, DP AF Faris, Jason E. Ryan, David P. TI Trees, Forests, and Other Implications of a BRAF Mutant Gene Signature in Patients With BRAF Wild-Type Disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID METASTATIC COLORECTAL-CANCER; II COLON-CANCER; STAGE-II; MUTATIONS; TRIAL; KRAS; VALIDATION; PETACC-3; SURVIVAL; POLYPS C1 [Faris, Jason E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Faris, JE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 29 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2012 VL 30 IS 12 BP 1255 EP 1257 DI 10.1200/JCO.2011.41.1512 PG 3 WC Oncology SC Oncology GA 938TR UT WOS:000303756500005 PM 22393091 ER PT J AU Pirl, WF Greer, JA Traeger, L Jackson, V Lennes, IT Gallagher, ER Perez-Cruz, P Heist, RS Temel, JS AF Pirl, William F. Greer, Joseph A. Traeger, Lara Jackson, Vicki Lennes, Inga T. Gallagher, Emily R. Perez-Cruz, Pedro Heist, Rebecca S. Temel, Jennifer S. TI Depression and Survival in Metastatic Non-Small-Cell Lung Cancer: Effects of Early Palliative Care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID STAGE-IV; MANAGEMENT; MORTALITY; DIAGNOSIS; SYMPTOMS; TRIAL AB Purpose In a randomized trial, early palliative care (EPC) in patients with metastatic non-small-cell lung cancer (NSCLC) was observed to improve survival. In a secondary analysis, we explored the hypothesis that the survival benefit resulted from improving depression. Patients and Methods In total, 151 patients with newly diagnosed metastatic NSCLC participated in a randomized trial of EPC integrated with standard oncology care versus standard oncology care alone. Depression was assessed at baseline and at 12 weeks with the Patient Health Questionnaire-9 (PHQ-9) and was scored diagnostically by using Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria for major depression syndrome (MDS). Depression response was considered >= 50% reduction in PHQ-9 scores at 12 weeks. Survival differences were tested with log-rank and Cox proportional hazards models. Results At baseline, 21 patients (14%) met MDS criteria. MDS significantly predicted worse survival (hazard ratio, 1.82; P = .02). Patients assigned to EPC had greater improvements in PHQ-9 scores at 12 weeks (P < .001); among patients with MDS, those receiving EPC had greater rates of depression response at 12 weeks (P = .04). However, improvement in PHQ-9 scores was not associated with improved survival, except in a sensitivity analysis in which patients who died before 12 weeks were modeled to have worse depression. The group randomly assigned to EPC remained independently associated with survival after adding improvement in PHQ-9 scores to the survival model. Conclusion Depression predicted worse survival in patients with newly diagnosed metastatic NSCLC. Although EPC was associated with greater improvement in depression at 12 weeks, the data do not support the hypothesis that treatment of depression mediated the observed survival benefit from EPC. C1 [Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA. RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Yawkey 9A,55 Fruit St, Boston, MA 02114 USA. EM wpirl@partners.org FU American Society of Clinical Oncology; National Cancer Institute, National Institutes of Health [K23 CA115908]; Forest Pharmaceuticals FX Supported by American Society of Clinical Oncology Career Development Award (J.S.T.) and Grant No. K23 CA115908 from the National Cancer Institute, National Institutes of Health (W.F.P.).; Research Funding: William F. Pirl, Forest Pharmaceuticals NR 26 TC 65 Z9 65 U1 2 U2 19 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 APR 20 PY 2012 VL 30 IS 12 BP 1310 EP 1315 DI 10.1200/JCO.2011.38.3166 PG 6 WC Oncology SC Oncology GA 938TR UT WOS:000303756500015 PM 22430269 ER PT J AU Finkelman, BS Rubinstein, WS Friedman, S Friebel, TM Dubitsky, S Schonberger, NS Shoretz, R Singer, CF Blum, JL Tung, N Olopade, OI Weitzel, JN Lynch, HT Snyder, C Garber, JE Schildkraut, J Daly, MB Isaacs, C Pichert, G Neuhausen, SL Couch, FJ van't Veer, L Eeles, R Bancroft, E Evans, DG Ganz, PA Tomlinson, GE Narod, SA Matloff, E Domchek, S Rebbeck, TR AF Finkelman, Brian S. Rubinstein, Wendy S. Friedman, Sue Friebel, Tara M. Dubitsky, Shera Schonberger, Niecee Singer Shoretz, Rochelle Singer, Christian F. Blum, Joanne L. Tung, Nadine Olopade, Olufunmilayo I. Weitzel, Jeffrey N. Lynch, Henry T. Snyder, Carrie Garber, Judy E. Schildkraut, Joellen Daly, Mary B. Isaacs, Claudine Pichert, Gabrielle Neuhausen, Susan L. Couch, Fergus J. van't Veer, Laura Eeles, Rosalind Bancroft, Elizabeth Evans, D. Gareth Ganz, Patricia A. Tomlinson, Gail E. Narod, Steven A. Matloff, Ellen Domchek, Susan Rebbeck, Timothy R. TI Breast and Ovarian Cancer Risk and Risk Reduction in Jewish BRCA1/2 Mutation Carriers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ASHKENAZI JEWS; GERMLINE MUTATIONS; SALPINGO-OOPHORECTOMY; ORAL-CONTRACEPTIVES; 6174DELT MUTATIONS; COST-EFFECTIVENESS; PENETRANCE; FAMILIES; WOMEN; GENE AB Purpose Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. Methods Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. Results Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups. Conclusion Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care. C1 [Finkelman, Brian S.; Friebel, Tara M.; Domchek, Susan; Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Rubinstein, Wendy S.] NorthShore Univ HealthSyst, Evanston, IL USA. [Olopade, Olufunmilayo I.] Univ Chicago, Chicago, IL 60637 USA. [Friedman, Sue] FORCE Facing Our Risk Canc Empowered, Tampa, FL USA. [Dubitsky, Shera; Schonberger, Niecee Singer; Shoretz, Rochelle] Sharsheret, Teaneck, NJ USA. [Blum, Joanne L.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Tomlinson, Gail E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Tomlinson, Gail E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weitzel, Jeffrey N.; Neuhausen, Susan L.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Weitzel, Jeffrey N.; Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Lynch, Henry T.; Snyder, Carrie] Creighton Univ, Omaha, NE 68178 USA. [Schildkraut, Joellen] Duke Univ, Med Ctr, Durham, NC USA. [Isaacs, Claudine] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. [Couch, Fergus J.] Mayo Clin, Coll Med, Rochester, MN USA. [Matloff, Ellen] Yale Canc Ctr, New Haven, CT USA. [Singer, Christian F.] Med Univ Vienna, Vienna, Austria. [Pichert, Gabrielle] Guys Hosp, London SE1 9RT, England. [Eeles, Rosalind; Bancroft, Elizabeth] Inst Canc Res, Sutton, Surrey, England. [Eeles, Rosalind; Bancroft, Elizabeth] Royal Marsden Natl Hlth Serv Trust, Sutton, Surrey, England. [Evans, D. Gareth] St Marys Hosp, Manchester M13 0JH, Lancs, England. [van't Veer, Laura] Netherlands Canc Inst, Amsterdam, Netherlands. [Narod, Steven A.] Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, 217 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rebbeck@exchange.upenn.edu OI Finkelman, Brian/0000-0002-4348-8208; Eeles, Rosalind/0000-0002-3698-6241; Evans, Gareth/0000-0002-8482-5784 FU National Institutes of Health (NIH) [R01-CA083855, R01-CA102776, T32-GM07170]; University of Pennsylvania School of Medicine; Cancer Genetics Network; National Cancer Institute [P30-CA051008-17]; National Institute for Health Research; Royal Marsden National Health Service (NHS) Foundation Trust; Cancer Research United Kingdom [C5047/A8385]; Tepnel (Gen-Probe); Vista Diagnostics; Illumina FX Supported by National Institutes of Health (NIH) Grants No. R01-CA083855 and R01-CA102776 (T. R. R.) and by Medical Scientist Training Program Grant No. T32-GM07170 from the NIH, as well as institutional funds from the University of Pennsylvania School of Medicine (B. S. F.). C. I. is supported by the Cancer Genetics Network and by National Cancer Institute Grant No. P30-CA051008-17. R. E. also receives support from the National Institute for Health Research to The Biomedical Research Center at The Institute of Cancer Research and Royal Marsden National Health Service (NHS) Foundation Trust. Part of the Carrier Clinic at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust receives support from Cancer Research United Kingdom Grant No. C5047/A8385.; Research Funding: Rosalind Eeles, Tepnel (Gen-Probe), Vista Diagnostics, Illumina NR 55 TC 13 Z9 13 U1 0 U2 4 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 APR 20 PY 2012 VL 30 IS 12 BP 1321 EP 1328 DI 10.1200/JCO.2011.37.8133 PG 8 WC Oncology SC Oncology GA 938TR UT WOS:000303756500017 PM 22430266 ER PT J AU Hellwig, S Miduturu, CV Kanda, S Zhang, JM Filippakopoulos, P Salah, E Deng, XM Choi, HG Zhou, WJ Hur, W Knapp, S Gray, NS Smithgall, TE AF Hellwig, Sabine Miduturu, Chandra V. Kanda, Shigeru Zhang, Jianming Filippakopoulos, Panagis Salah, Eidarus Deng, Xianming Choi, Hwan Geun Zhou, Wenjun Hur, Wooyoung Knapp, Stefan Gray, Nathanael S. Smithgall, Thomas E. TI Small-Molecule Inhibitors of the c-Fes Protein-Tyrosine Kinase SO CHEMISTRY & BIOLOGY LA English DT Article ID SRC HOMOLOGY-2 DOMAIN; TRANSFORMING ACTIVITIES; COLORECTAL-CANCER; GENE-EXPRESSION; COILED-COIL; SH2 DOMAINS; F-BAR; CELLS; ACTIVATION; FPS/FES AB The c-Fes protein-tyrosine kinase modulates cellular signaling pathways governing differentiation, the innate immune response, and vasculogenesis. Here, we report the identification of types I and II kinase inhibitors with potent activity against c-Fes both in vitro and in cell-based assays. One of the most potent inhibitors is the previously described anaplastic lymphoma kinase inhibitor TAE684. The crystal structure of TAE684 in complex with the c-Fes SH2-kinase domain showed excellent shape complementarity with the ATP-binding pocket and a key role for the gatekeeper methionine in the inhibitory mechanism. TAE684 and two pyrazolopyrimidines with nanomolar potency against c-Fes in vitro were used to establish a role for this kinase in osteoclastogenesis, illustrating the value of these inhibitors as tool compounds to probe the diverse biological functions associated with this unique kinase. C1 [Hellwig, Sabine; Smithgall, Thomas E.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA. [Miduturu, Chandra V.; Zhang, Jianming; Deng, Xianming; Choi, Hwan Geun; Zhou, Wenjun; Hur, Wooyoung; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Miduturu, Chandra V.; Zhang, Jianming; Deng, Xianming; Choi, Hwan Geun; Zhou, Wenjun; Hur, Wooyoung; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kanda, Shigeru] Nagasaki Univ, Dept Mol Microbiol & Immunol, Grad Sch Biomed Sci, Nagasaki 8528523, Japan. [Kanda, Shigeru] Nagasaki Hosp, Natl Hosp Org, Dept Expt & Clin Lab Med, Nagasaki 8508523, Japan. [Filippakopoulos, Panagis; Salah, Eidarus; Knapp, Stefan] Univ Oxford, SGC, Nuffield Dept Clin Med, Oxford OX3 7BN, England. RP Smithgall, TE (reprint author), Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA. EM tsmithga@pitt.edu OI Filippakopoulos, Panagis/0000-0002-1515-1317; Knapp, Stefan/0000-0001-5995-6494 FU National Institutes of Health [CA123756, GM079575, CA130876]; Canadian Institutes for Health Research; Canadian Foundation for Innovation; Genome Canada through the Ontario Genomics Institute; GlaxoSmithKline; Karolinska Institute; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Merck Co., Inc.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust FX This work was supported by the National Institutes of Health (grants CA123756 to T.S. and GM079575 and CA130876 to N.S.G.). The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, the Karolinska Institute, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co., Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research, and the Wellcome Trust. We thank Dr. Ritsuko Masuyama, Nagasaki University Graduate School of Biomedical Sciences, for expert assistance with the isolation and culture of mouse bone marrow macrophages. NR 56 TC 7 Z9 7 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD APR 20 PY 2012 VL 19 IS 4 BP 529 EP 540 DI 10.1016/j.chembiol.2012.01.020 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 933OL UT WOS:000303371500015 PM 22520759 ER PT J AU Sassower, KC Allister, LM Westra, SJ AF Sassower, Kenneth C. Allister, Lauren M. Westra, Sjirk J. TI Case 12-2012: A 10-Month-Old Girl with Vomiting and Episodes of Unresponsiveness SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PLAIN FILM DIAGNOSIS; INTUSSUSCEPTION; CHILDREN; MANAGEMENT C1 [Sassower, Kenneth C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Allister, Lauren M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Westra, Sjirk J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sassower, Kenneth C.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Westra, Sjirk J.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Allister, Lauren M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Sassower, KC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU Massachusetts General Hospital for Children; Harvard Medical School Department of Continuing Education FX Presented at the postgraduate course Primary Care Pediatrics (course directors: Peter T. Greenspan, M.D., Ronald E. Kleinman, M.D., John Patrick T. Co, M.D., M.P.H., Ronni L. Goldsmith, M.D., and Janice A. Lowe, M.D.), sponsored by Massachusetts General Hospital for Children and Harvard Medical School Department of Continuing Education. NR 27 TC 1 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 APR 19 PY 2012 VL 366 IS 16 BP 1527 EP 1536 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 927UE UT WOS:000302934800012 PM 22512486 ER PT J AU Czuczman, MS Fayad, L Delwail, V Cartron, G Jacobsen, E Kuliczkowski, K Link, BK Pinter-Brown, L Radford, J Hellmann, A Gallop-Evans, E DiRienzo, CG Goldstein, N Gupta, I Jewell, RC Lin, TS Lisby, S Schultz, M Russell, CA Hagenbeek, A AF Czuczman, Myron S. Fayad, Luis Delwail, Vincent Cartron, Guillaume Jacobsen, Eric Kuliczkowski, Kazimierz Link, Brian K. Pinter-Brown, Lauren Radford, John Hellmann, Andrzej Gallop-Evans, Eve DiRienzo, Christine G. Goldstein, Nancy Gupta, Ira Jewell, Roxanne C. Lin, Thomas S. Lisby, Steen Schultz, Martin Russell, Charlotte A. Hagenbeek, Anton CA 405 Study Investigators TI Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study SO BLOOD LA English DT Article ID ANTI-CD20 MONOCLONAL-ANTIBODY; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; CHEMOTHERAPY PLUS RITUXIMAB; HUMAN CD20; PHASE-II; MAINTENANCE THERAPY; RESPONSE CRITERIA; I-131 TOSITUMOMAB AB New treatments are required for rituximab-refractory follicular lymphoma (FL). In the present study, patients with rituximab-refractory FL received 8 weekly infusions of ofatumumab (CD20 mAb; dose 1, 300 mg and doses 2-8, 500 or 1000 mg; N = 116). The median age of these patients was 61 years, 47% had high-risk Follicular Lymphoma International Prognostic Index scores, 65% were chemotherapy-refractory, and the median number of prior therapies was 4. The overall response rate was 13% and 10% for the 500-mg and 1000-mg arms, respectively. Among 27 patients refractory to rituximab monotherapy, the overall response rate was 22%. The median progression-free survival was 5.8 months. Forty-six percent of patients demonstrated tumor reduction 3 months after therapy initiation, and the median progression-free survival for these patients was 9.1 months. The most common adverse events included infections, rash, urticaria, fatigue, and pruritus. Threepatientsexperiencedgrade3infusion-related reactions, none of which were considered serious events. Grade 3-4 neutropenia, leukopenia, anemia, and thrombocytopenia occurred in a subset of patients. Ofatumumab was well tolerated and modestly active in this heavily pretreated, rituximab-refractory population and is therefore now being studied in less refractory FL and in combination with other agents in various B-cell neoplasms. The present study was registered at www.clinicaltrials.gov as NCT00394836. (Blood. 2012;119(16):3698-3704) C1 [Czuczman, Myron S.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. [Fayad, Luis] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Delwail, Vincent] Ctr Hosp Univ Poitiers, Ctr Invest Clin Inserm 0802, Poitiers, France. [Cartron, Guillaume] CHU Montpellier, Serv Hematol, Unite Mixte Rech 5235, Montpellier, France. [Jacobsen, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kuliczkowski, Kazimierz] Klin Hematol Nowotworow Krwi & Transplantacji Szp, Wroclaw, Poland. [Link, Brian K.] Univ Iowa, Iowa City, IA USA. [Pinter-Brown, Lauren] Univ Calif Los Angeles, Los Angeles, CA USA. [Radford, John] Christie Natl Hlth Serv Fdn Trust, Manchester, Lancs, England. [Radford, John] Univ Manchester, Manchester, Lancs, England. [Hellmann, Andrzej] Med Univ Gdansk, Dept Hematol & Transplantol, Gdansk, Poland. [Gallop-Evans, Eve] Velindre Hosp, Cardiff, S Glam, Wales. [DiRienzo, Christine G.; Gupta, Ira; Lin, Thomas S.] GlaxoSmithKline, Collegeville, PA USA. [Goldstein, Nancy; Jewell, Roxanne C.] GlaxoSmithKline, Res Triangle Pk, NC USA. [Lisby, Steen; Schultz, Martin; Russell, Charlotte A.] Genmab, Copenhagen, Denmark. [Hagenbeek, Anton] Univ Amsterdam, Acad Med Ctr, Dept Hematol, NL-1105 AZ Amsterdam, Netherlands. RP Czuczman, MS (reprint author), Roswell Pk Canc Inst, Dept Med, Elm & Carlton St, Buffalo, NY 14263 USA. EM myron.czuczman@roswellpark.org RI Radford, John/N-1331-2015; OI Radford, John/0000-0001-7898-2786; Delwail, Vincent/0000-0003-0680-1418 FU Genmab A/S; GlaxoSmithKline; Genmab; Genentech/Roche; Lilly FX This study was supported by research funding from Genmab A/S and GlaxoSmithKline. Editorial support for this publication was provided by Emily Bauer, PhD, Medicus International New York, and was funded by GlaxoSmithKline.; M.S.C. acted as a consultant/advisor for GSK and Genmab and received research funding from Genmab. L.F. received research funding from GSK. G.C. acted as a consultant/advisor for Roche and GSK and received honoraria from GlaxoSmithKline and Roche. B.K.L. acted as a consultant/advisor for Genentech/Roche and GlaxoSmithKline and received research funding from Genentech/Roche, Lilly, and GlaxoSmithKline. J.R. acted as a consultant/advisor for GlaxoSmithKline and owns stock in GlaxoSmithKline. A. Hellmann received research funding from Genmab and GSK. C.G.D. is an employee of GSK. N.G. is an employee of and owns stock in GlaxoSmithKline. I.G. is an employee of and owns stock in GSK. R.C.J. is an employee of and owns stock in GSK. T.S.L. is an employee of GSK. S.L. is an employee of Genmab. M.S. is an employee of and owns stock in Genmab. C.A.R. was an employee of Genmab when the study took place, is currently employed at Boehringer Ingelheim, and owns stock in Genmab. A. Hagenbeek acted as a consultant/advisor for Spectrum Pharmaceuticals. The remaining authors declare no competing financial interests. NR 39 TC 53 Z9 61 U1 1 U2 4 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 APR 19 PY 2012 VL 119 IS 16 BP 3698 EP 3704 DI 10.1182/blood-2011-09-378323 PG 7 WC Hematology SC Hematology GA 959AM UT WOS:000305282100013 PM 22389254 ER PT J AU Levine, JE Logan, BR Wu, J Alousi, AM Bolanos-Meade, J Ferrara, JLM Ho, VT Weisdorf, DJ Paczesny, S AF Levine, John E. Logan, Brent R. Wu, Juan Alousi, Amin M. Bolanos-Meade, Javier Ferrara, James L. M. Ho, Vincent T. Weisdorf, Daniel J. Paczesny, Sophie TI Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study SO BLOOD LA English DT Article ID TUMOR-MARKERS; ACUTE GVHD; SURVIVAL; BREAST AB Acute graft-versus-host disease (GVHD) is the primary limitation of allogeneic hematopoietic cell transplantation, and once it develops, there are no reliable diagnostic tests to predict treatment outcomes. We hypothesized that 6 previously validated diagnostic biomarkers of GVHD (IL-2 receptor-alpha; tumor necrosis factor receptor-1; hepatocyte growth factor; IL-8; elafin, a skin-specific marker; and regenerating islet-derived 3-alpha, a gastrointestinal tract-specific marker) could discriminate between therapy responsive and nonresponsive patients and predict survival in patients receiving GVHD therapy. We measured GVHD biomarker concentrations from samples prospectively obtained at the initiation of treatment, day 14, and day 28, on a multicenter, randomized, 4-arm phase 2 clinical trial for newly diagnosed acute GVHD. We found that at each of 3 time points, GVHD onset, 2 weeks into treatment, and 4 weeks into treatment, a 6-protein biomarker panel predicted for the important clinical outcomes of day 28 posttherapy nonresponse and mortality at day 180 from onset. GVHD biomarker panels can be used for early identification of patients at high or low risk for treatment nonresponsiveness or death, and they may provide opportunities for early intervention and improved survival after hematopoietic cell transplantation. The study was registered in clinicaltrials.gov as NCT00224874. (Blood. 2012;119(16):3854-3860) C1 [Levine, John E.; Paczesny, Sophie] Univ Michigan, Ctr Comprehens Canc, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Milwaukee, MN USA. [Wu, Juan] EMMES Corp, Rockville, MD USA. [Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Houston, TX 77030 USA. [Bolanos-Meade, Javier] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Ho, Vincent T.] Dana Farber Harvard Canc Inst, Boston, MA USA. [Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA. RP Levine, JE (reprint author), Univ Michigan, Ctr Comprehens Canc, Blood & Marrow Transplant Program, Rm 6410,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM jelevine@med.umich.edu; sophiep@med.umich.edu OI Levine, John/0000-0002-9133-0800 FU Blood and Marrow Transplant Clinical Trials National Heart, Lung, and Blood Institute [U01HL069294]; National Cancer Institute; National Institute of Allergy and Infectious Diseases; National Institutes of Health [065528] FX This work was supported in part by the Blood and Marrow Transplant Clinical Trials grant U01HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute and by the National Institute of Allergy and Infectious Diseases and National Institutes of Health National Marrow Donor Program subcontract 065528. NR 15 TC 71 Z9 74 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 19 PY 2012 VL 119 IS 16 BP 3854 EP 3860 DI 10.1182/blood-2012-01-403063 PG 7 WC Hematology SC Hematology GA 959AM UT WOS:000305282100030 PM 22383800 ER PT J AU McEwan, DL Kirienko, NV Ausubel, FM AF McEwan, Deborah L. Kirienko, Natalia V. Ausubel, Frederick M. TI Host Translational Inhibition by Pseudomonas aeruginosa Exotoxin A Triggers an Immune Response in Caenorhabditis elegans SO CELL HOST & MICROBE LA English DT Article ID LIFE-SPAN EXTENSION; C. ELEGANS; SIGNALING PATHWAY; VIRULENCE FACTORS; GENE-EXPRESSION; PATHOGEN; SYSTEM; MECHANISMS; EVOLUTION; INFECTION AB Intestinal epithelial cells are exposed to both innocuous and pathogenic microbes, which need to be distinguished to mount an effective immune response. To understand the mechanisms underlying pathogen recognition, we investigated how Pseudomonas aeruginosa triggers intestinal innate immunity in Caenorhabditis elegans, a process independent of Toll-like pattern recognition receptors. We show that the P. aeruginosa translational inhibitor Exotoxin A (ToxA), which ribosylates elongation factor 2 (EF2), upregulates a significant subset of genes normally induced by P. aeruginosa. Moreover, immune pathways involving the ATF-7 and ZIP-2 transcription factors, which protect C. elegans from P. aeruginosa, are required for preventing ToxA-mediated lethality. ToxA-responsive genes are not induced by enzymatically inactive ToxA protein but can be upregulated independently of ToxA by disruption of host protein translation. Thus, C. elegans has a surveillance mechanism to recognize ToxA through its effect on protein translation rather than by direct recognition of either ToxA or ribosylated EF2. C1 [McEwan, Deborah L.; Kirienko, Natalia V.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [McEwan, Deborah L.; Kirienko, Natalia V.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu FU Massachusetts Biomedical Research Corporation (MBRC); National Institutes of Health (NIH) [R01 AI085581, P30 DK040561] FX We are grateful to the Caenorhabditis Genetics Center (CGC), Min Han, Laurence Rahme, and Keith Blackwell for C. elegans and bacterial strains and to Lynda Stuart and members of the Ausubel lab for critical reading of the manuscript. We also thank Emily Troemel, Gary Ruvkun, and members of the Ruvkun lab, particularly Justine Melo, Van Qi, and Dave Shore, for helpful discussions and for sharing unpublished data. This work was supported by the Massachusetts Biomedical Research Corporation (MBRC) Tosteson Postdoctoral Fellowship Award and by National Institutes of Health (NIH) grants R01 AI085581 and P30 DK040561. NR 51 TC 69 Z9 74 U1 3 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD APR 19 PY 2012 VL 11 IS 4 BP 364 EP 374 DI 10.1016/j.chom.2012.02.007 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 935BH UT WOS:000303491500007 PM 22520464 ER PT J AU Hwang, S Maloney, NS Bruinsma, MW Goel, G Duan, EN Zhang, L Shrestha, B Diamond, MS Dani, A Sosnovtsev, SV Green, KY Lopez-Otin, C Xavier, RJ Thackray, LB Virgin, HW AF Hwang, Seungmin Maloney, Nicole S. Bruinsma, Monique W. Goel, Gautam Duan, Erning Zhang, Lei Shrestha, Bimmi Diamond, Michael S. Dani, Adish Sosnovtsev, Stanislav V. Green, Kim Y. Lopez-Otin, Carlos Xavier, Ramnik J. Thackray, Larissa B. Virgin, Herbert W. TI Nondegradative Role of Atg5-Atg12/Atg16L1 Autophagy Protein Complex in Antiviral Activity of Interferon Gamma SO CELL HOST & MICROBE LA English DT Article ID SECRETORY PATHWAY; VIRUS-INFECTION; IMMUNITY; REPLICATION; LC3; INFLAMMATION; MACROPHAGES; BIOGENESIS; LIPIDATION; ACTIVATION AB Host resistance to viral infection requires type I (alpha/beta) and II (gamma) interferon (IFN) production. Another important defense mechanism is the degradative activity of macroautophagy (herein autophagy), mediated by the coordinated action of evolutionarily conserved autophagy proteins (Atg). We show that the Atg5-Atg12/Atg16L1 protein complex, whose prior known function is in autophagosome formation, is required for IFN gamma-mediated host defense against murine norovirus (MNV) infection. Importantly, the direct antiviral activity of IFN gamma against MNV in macrophages required Atg5-Atg12, Atg7, and Atg16L1, but not induction of autophagy, the degradative activity of lysosomal proteases, fusion of autophagosomes and lysosomes, or the Atg8-processing protein Atg4B. IFN gamma, via Atg5-Atg12/Atg16L1, inhibited formation of the membranous cytoplasmic MNV replication complex, where Atg16L1 localized. Thus, the Atg5-Atg12/Atg16L1 complex performs a pivotal, nondegradative role in IFN gamma-mediated antiviral defense, establishing that multicellular organisms have evolved to use portions of the autophagy pathway machinery in a cassette-like fashion for host defense. C1 [Hwang, Seungmin; Maloney, Nicole S.; Bruinsma, Monique W.; Duan, Erning; Zhang, Lei; Dani, Adish; Thackray, Larissa B.; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Shrestha, Bimmi; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Goel, Gautam; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Goel, Gautam; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Sosnovtsev, Stanislav V.; Green, Kim Y.] NIAID, Infect Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lopez-Otin, Carlos] Univ Oviedo, Inst Univ Oncol, Fac Med, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain. RP Thackray, LB (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. EM thackray@wustl.edu; virgin@wustl.edu RI zhou, zhenqing/H-4580-2014; Duan, Erning /H-4608-2014; Lopez-Otin, Carlos/C-6657-2013; OI Lopez-Otin, Carlos/0000-0001-6964-1904; Hwang, Seungmin/0000-0003-0846-5462 FU Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases [U54 AI065982]; National Institutes of Health [AI054483, CA096511, AI084887]; Rheumatic Diseases Core Center [NIH P30 AR48335]; NCI Cancer Center [P30 CA91842]; ICTS/CTSA [UL1RR024992]; Ministry of Science and Innovation-Spain; Fundacion M. Botin FX This work was supported by the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (U54 AI065982), National Institutes of Health grants AI054483, CA096511, and AI084887, and the Rheumatic Diseases Core Center (NIH P30 AR48335). We thank the Genome Technology Access Center at Washington University School of Medicine for help with genomic analysis (supported by NCI Cancer Center Support Grant number P30 CA91842 and ICTS/CTSA grant number UL1RR024992). Washington University and H.W.V. receive income based on licenses for MNV technology. C.L.O. was supported by grants from Ministry of Science and Innovation-Spain, FP7 (Microenvimet), and Fundacion M. Botin. We would like to thank Masaaki Komatsu (Tokyo Metropolitan Institute of Medical Science, Japan) for Atg7F/F mouse, Noboru Mizushima (Tokyo Medical and Dental University, Japan) for Atg5F/F mouse, Tamotsu Yoshimori (Osaka University, Japan) for Atg4B/C74A and Rab7A/T22N constructs. We thank Virgin lab members for their comments on the manuscript and D. Kreamalmeyer and M. White for managing mouse colonies. NR 46 TC 77 Z9 78 U1 3 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD APR 19 PY 2012 VL 11 IS 4 BP 397 EP 409 DI 10.1016/j.chom.2012.03.002 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 935BH UT WOS:000303491500010 PM 22520467 ER PT J AU Weintraub, WS Grau-Sepulveda, MV Weiss, JM O'Brien, SM Peterson, ED Kolm, P Zhang, ZG Klein, LW Shaw, RE McKay, C Ritzenthaler, LL Popma, JJ Messenger, JC Shahian, DM Grover, FL Mayer, JE Shewan, CM Garratt, KN Moussa, ID Dangas, GD Edwards, FH AF Weintraub, William S. Grau-Sepulveda, Maria V. Weiss, Jocelyn M. O'Brien, Sean M. Peterson, Eric D. Kolm, Paul Zhang, Zugui Klein, Lloyd W. Shaw, Richard E. McKay, Charles Ritzenthaler, Laura L. Popma, Jeffrey J. Messenger, John C. Shahian, David M. Grover, Frederick L. Mayer, John E. Shewan, Cynthia M. Garratt, Kirk N. Moussa, Issam D. Dangas, George D. Edwards, Fred H. TI Comparative Effectiveness of Revascularization Strategies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; BYPASS-SURGERY; MULTIVESSEL DISEASE; FOLLOW-UP; PERCUTANEOUS REVASCULARIZATION; STENT IMPLANTATION; RANDOMIZED TRIAL; ANGIOPLASTY; INTERVENTION; PROPENSITY AB Background Questions persist concerning the comparative effectiveness of percutaneous coronary intervention (PCI) and coronary-artery bypass grafting (CABG). The American College of Cardiology Foundation (ACCF) and the Society of Thoracic Surgeons (STS) collaborated to compare the rates of long-term survival after PCI and CABG. Methods We linked the ACCF National Cardiovascular Data Registry and the STS Adult Cardiac Surgery Database to claims data from the Centers for Medicare and Medicaid Services for the years 2004 through 2008. Outcomes were compared with the use of propensity scores and inverse-probability-weighting adjustment to reduce treatment-selection bias. Results Among patients 65 years of age or older who had two-vessel or three-vessel coronary artery disease without acute myocardial infarction, 86,244 underwent CABG and 103,549 underwent PCI. The median follow-up period was 2.67 years. At 1 year, there was no significant difference in adjusted mortality between the groups (6.24% in the CABG group as compared with 6.55% in the PCI group; risk ratio, 0.95; 95% confidence interval [CI], 0.90 to 1.00). At 4 years, there was lower mortality with CABG than with PCI (16.4% vs. 20.8%; risk ratio, 0.79; 95% CI, 0.76 to 0.82). Similar results were noted in multiple subgroups and with the use of several different analytic methods. Residual confounding was assessed by means of a sensitivity analysis. Conclusions In this observational study, we found that, among older patients with multivessel coronary disease that did not require emergency treatment, there was a long-term survival advantage among patients who underwent CABG as compared with patients who underwent PCI. (Funded by the National Heart, Lung, and Blood Institute.) C1 [Weintraub, William S.] Christiana Care Hlth Syst, Cardiol Sect, Newark, DE 19718 USA. [Grau-Sepulveda, Maria V.; O'Brien, Sean M.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Weiss, Jocelyn M.; Ritzenthaler, Laura L.] Amer Coll Cardiol, Washington, DC USA. [Klein, Lloyd W.] Advocate Illinois Masonic Med Ctr, Chicago, IL USA. [Shewan, Cynthia M.] Soc Thorac Surg, Chicago, IL USA. [Shaw, Richard E.] Calif Pacific Med Ctr, San Francisco, CA USA. [McKay, Charles] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Popma, Jeffrey J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mayer, John E.] Childrens Hosp, Boston, MA 02115 USA. [Messenger, John C.; Grover, Frederick L.] Univ Colorado, Sch Med, Aurora, CO USA. [Grover, Frederick L.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Garratt, Kirk N.] Lenox Hill Heart & Vasc Inst New York, New York, NY USA. [Dangas, George D.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Moussa, Issam D.] Mayo Clin, Jacksonville, FL USA. [Edwards, Fred H.] Univ Florida, Jacksonville, FL USA. RP Weintraub, WS (reprint author), Christiana Care Hlth Syst, Cardiol Sect, 4755 Ogletown Stanton Rd, Newark, DE 19718 USA. EM wweintraub@christianacare.org RI O'Brien, Sean/H-6268-2013; 刘, 李陆/H-8469-2015 FU National Heart, Lung, and Blood Institute [RC2HL101489]; Abbott Vascular; Boston Scientific; Covidien; Abiomed; Cordis; Medtronic; AstraZeneca; Eli Lilly; Johnson Johnson; Ogilvy; Bristol-Myers Squibb; Daichi-Sankyo; Medicines Company; Sanofi-Aventis; Bracco; Guerbet FX Supported by a grant (RC2HL101489) from the National Heart, Lung, and Blood Institute.; Dr. Popma reports receiving consulting fees from Abbott Vascular, Boston Scientific, and Covidien and grant support from Abbott Vascular, Abiomed, Boston Scientific, Cordis, and Medtronic; Dr. Messenger, receiving grant support from Medtronic; Dr. Mayer, receiving honoraria and reimbursement for travel expenses from CHMC Cardiovascular Surgical Foundation; Dr. Dangas, receiving consulting fees from Abbott Vascular, AstraZeneca, Eli Lilly, Johnson & Johnson, and Ogilvy, providing expert testimony regarding stroke in a patient after cardioversion for atrial fibrillation and regarding infection after heart-valve implantation, and receiving grant support from Bristol-Myers Squibb, Eli Lilly, Daichi-Sankyo, the Medicines Company, and Sanofi-Aventis, lecture fees from Abbott Vascular, AstraZeneca, Boston Scientific, Bracco, Bristol-Myers Squibb, Guerbet, Eli Lilly, Johnson & Johnson, the Medicines Company, and Sanofi-Aventis, royalties from Wiley and Informa, and reimbursement for travel expenses from the Cardiovascular Research Foundation; and Dr. Edwards, being an employee of the Society of Thoracic Surgeons. No other potential conflict of interest relevant to this article was reported. NR 34 TC 233 Z9 247 U1 1 U2 14 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 APR 19 PY 2012 VL 366 IS 16 BP 1467 EP 1476 DI 10.1056/NEJMoa1110717 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 927UE UT WOS:000302934800004 PM 22452338 ER PT J AU Shipley, WU Zietman, AL AF Shipley, William U. Zietman, Anthony L. TI Old Drugs, New Purpose - Bladder Cancer Turning a Corner SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PRESERVATION; CYSTECTOMY; THERAPY C1 [Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Shipley, WU (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 9 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 APR 19 PY 2012 VL 366 IS 16 BP 1540 EP 1541 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 927UE UT WOS:000302934800014 PM 22512487 ER PT J AU Grover, FL AF Grover, Frederick L. TI Current Status of Off-Pump Coronary-Artery Bypass SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RANDOMIZED-TRIAL; ON-PUMP; SURGERY C1 [Grover, Frederick L.] Univ Colorado, Sch Med, Dept Surg, Denver, CO 80202 USA. [Grover, Frederick L.] Denver Vet Affairs Med Ctr, Cardiothorac Surg Sect, Denver, CO USA. RP Grover, FL (reprint author), Univ Colorado, Sch Med, Dept Surg, Denver, CO 80202 USA. NR 6 TC 2 Z9 2 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 19 PY 2012 VL 366 IS 16 BP 1541 EP 1543 DI 10.1056/NEJMe1203194 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 927UE UT WOS:000302934800015 PM 22449294 ER PT J AU Hope, MD Dyverfeldt, P Acevedo-Bolton, G Wrenn, J Foster, E Tseng, E Saloner, D AF Hope, Michael D. Dyverfeldt, Petter Acevedo-Bolton, Gabriel Wrenn, Jarrett Foster, Elyse Tseng, Elaine Saloner, David TI Post-stenotic dilation: Evaluation of ascending aortic dilation with 4D flow MR imaging SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Aneurysm; Valve-related aortic disease; Post-stenotic dilation; Bicuspid aortic valve; 4D flow; Shear stress C1 [Hope, Michael D.; Dyverfeldt, Petter; Acevedo-Bolton, Gabriel; Wrenn, Jarrett; Saloner, David] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Foster, Elyse] Univ Calif San Francisco, Dept Cardiol, San Francisco, CA 94143 USA. [Tseng, Elaine] San Francisco VA Med Ctr, Dept Cardiothorac Surg, San Francisco, CA USA. RP Hope, MD (reprint author), Univ Calif San Francisco, Dept Radiol, 505 Parnassus Ave,Box 0628, San Francisco, CA 94143 USA. EM michael.hope@ucsf.edu OI Dyverfeldt, Petter/0000-0002-3051-661X FU NINDS NIH HHS [K25 NS058573] NR 5 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD APR 19 PY 2012 VL 156 IS 2 BP E40 EP E42 DI 10.1016/j.ijcard.2011.08.018 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 909QX UT WOS:000301580400006 PM 21907425 ER PT J AU Zhu, JY Sharma, DB Gray, SW Chen, AB Weeks, JC Schrag, D AF Zhu, Junya Sharma, Dhruv B. Gray, Stacy W. Chen, Aileen B. Weeks, Jane C. Schrag, Deborah TI Carboplatin and Paclitaxel With vs Without Bevacizumab in Older Patients With Advanced Non-Small Cell Lung Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SEER-MEDICARE DATA; PROPENSITY SCORE; TARGETED THERAPIES; COMORBIDITY INDEX; SUPPORTIVE CARE; CHEMOTHERAPY; CLAIMS; BIAS; EPIDEMIOLOGY; METAANALYSIS AB Context A previous randomized trial demonstrated that adding bevacizumab to carboplatin and paclitaxel improved survival in advanced non-small cell lung cancer (NSCLC). However, longer survival was not observed in the subgroup of patients aged 65 years or older. Objective To examine whether adding bevacizumab to carboplatin and paclitaxel chemotherapy is associated with improved survival in older patients with NSCLC. Design, Setting, and Participants Retrospective cohort study of 4168 Medicare beneficiaries aged 65 years or older with stage IIIB or stage IV non-squamous cell NSCLC diagnosed in 2002-2007 in a Surveillance, Epidemiology, and End Results (SEER) region. Patients were categorized into 3 cohorts based on diagnosis year and type of initial chemotherapy administered within 4 months of diagnosis: (1) diagnosis in 2006-2007 and bevacizumab-carboplatin-paclitaxel therapy; (2) diagnosis in 2006-2007 and carboplatin-paclitaxel therapy; or (3) diagnosis in 2002-2005 and carboplatin-paclitaxel therapy. The associations between carboplatin-paclitaxel with vs without bevacizumab and overall survival were compared using Cox proportional hazards models and propensity score analyses including information about patient characteristics recorded in SEER-Medicare. Main Outcome Measure Overall survival measured from the first date of chemotherapy treatment until death or the censoring date of December 31, 2009. Results The median survival estimates were 9.7 (interquartile range [IQR], 4.4-18.6) months for bevacizumab-carboplatin-paclitaxel, 8.9 (IQR, 3.5-19.3) months for carboplatin-paclitaxel in 2006-2007, and 8.0 (IQR, 3.7-17.2) months for carboplatin-paclitaxel in 2002-2005. One-year survival probabilities were 39.6% (95% CI, 34.6%-45.4%) for bevacizumab-carboplatin-paclitaxel vs 40.1% (95% CI, 37.4%-43.0%) for carboplatin-paclitaxel in 2006-2007 and 35.6% (95% CI, 33.8%-37.5%) for carboplatin-paclitaxel in 2002-2005. Neither multivariable nor propensity score-adjusted Cox models demonstrated a survival advantage for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel cohorts. In propensity score-stratified models, the hazard ratio for overall survival for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel in 2006-2007 was 1.01 (95% CI, 0.89-1.16; P=.85) and compared with carboplatin-paclitaxel in 2002-2005 was 0.93 (95% CI, 0.83-1.06; P=.28). The propensity score-weighted model and propensity score-matching model similarly failed to demonstrate a statistically significant superiority for bevacizumab-carboplatin-paclitaxel. Subgroup and sensitivity analyses for key variables did not change these findings. Conclusion Adding bevacizumab to carboplatin and paclitaxel chemotherapy was not associated with better survival among Medicare patients with advanced NSCLC. JAMA. 2012; 307(15):1593-1601 C1 [Chen, Aileen B.; Weeks, Jane C.; Schrag, Deborah] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02215 USA. [Zhu, Junya] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02215 USA. [Sharma, Dhruv B.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Gray, Stacy W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Chen, Aileen B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. RP Schrag, D (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 450 Brookline Ave, Boston, MA 02215 USA. EM deb_schrag@dfci.harvard.edu OI Chen, Aileen/0000-0002-5385-3360 FU National Cancer Institute (NCI) [RC2CA148185-01, PO1-CA134294]; Agency for Healthcare Research and Quality (AHRQ) [HHSA290201000006I]; NCI's SEER [N01-PC-35136, N01-PC-35139, N02-PC-15105]; Centers for Disease Control and Prevention [U55/CCR921930-02]; Center for Patient Safety, Dana-Farber Cancer Institute; Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Center for Outcomes and Evidence, AHRQ FX Project support was obtained from the National Cancer Institute (NCI) RC2CA148185-01 (to Dr Weeks). This project was also funded under contract HHSA290201000006I (to Dr Schrag) from the Agency for Healthcare Research and Quality (AHRQ) as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. Dr Sharma was supported by NCI grant PO1-CA134294. The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the NCI's SEER program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries under agreement U55/CCR921930-02 awarded to the Public Health Institute.; We acknowledge support from Saul Weingart, MD, PhD, Center for Patient Safety, Dana-Farber Cancer Institute; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; and William Lawrence, MD, MS, Center for Outcomes and Evidence, AHRQ. No financial compensation was received. This study used the linked SEER-Medicare database. This resource has been made available to the research community through collaborative efforts of the NCI and CMS. We acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS) Inc; and the SEER program tumor registries in the creation and ongoing maintenance of the SEER-Medicare database. NR 37 TC 61 Z9 63 U1 2 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 18 PY 2012 VL 307 IS 15 BP 1593 EP 1601 DI 10.1001/jama.2012.454 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 927GU UT WOS:000302896100021 PM 22511687 ER PT J AU Basch, E Aronson, N Berg, A Flum, D Gabriel, S Goodman, SN Helfand, M Ioannidis, JPA Lauer, M Meltzer, D Mittman, B Newhouse, R Normand, SL Schneeweiss, S Slutsky, J Tinetti, M Yancy, C AF Basch, Ethan Aronson, Naomi Berg, Alfred Flum, David Gabriel, Sherine Goodman, Steven N. Helfand, Mark Ioannidis, John P. A. Lauer, Michael Meltzer, David Mittman, Brian Newhouse, Robin Normand, Sharon-Lise Schneeweiss, Sebastian Slutsky, Jean Tinetti, Mary Yancy, Clyde CA Methodology Comm Patient-Centered TI Methodological Standards and Patient-Centeredness in Comparative Effectiveness Research The PCORI Perspective SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMPLEMENTATION-RESEARCH; RANDOMIZED-TRIALS; PROPENSITY SCORE; CLINICAL-TRIALS; QUALITY IMPROVEMENT; PUBLICATION BIAS; MEDICATIONS; EXPERIENCE; BENEFITS; LESSONS AB Rigorous methodological standards help to ensure that medical research produces information that is valid and generalizable, and are essential in patient-centered outcomes research (PCOR). Patient-centeredness refers to the extent to which the preferences, decision-making needs, and characteristics of patients are addressed, and is the key characteristic differentiating PCOR from comparative effectiveness research. The Patient Protection and Affordable Care Act signed into law in 2010 created the Patient-Centered Outcomes Research Institute (PCORI), which includes an independent, federally appointed Methodology Committee. The Methodology Committee is charged to develop methodological standards for PCOR. The 4 general areas identified by the committee in which standards will be developed are (1) prioritizing research questions, (2) using appropriate study designs and analyses, (3) incorporating patient perspectives throughout the research continuum, and (4) fostering efficient dissemination and implementation of results. A Congressionally mandated PCORI methodology report (to be issued in its first iteration in May 2012) will begin to provide standards in each of these areas, and will inform future PCORI funding announcements and review criteria. The work of the Methodology Committee is intended to enable generation of information that is relevant and trustworthy for patients, and to enable decisions that improve patient-centered outcomes. JAMA. 2012;307(15):1636-1640 www.jama.com C1 [Basch, Ethan] Mem Sloan Kettering Canc Ctr, Hlth Outcomes Res Grp, New York, NY 10463 USA. [Aronson, Naomi] Blue Cross Blue Shield Assoc, Chicago, IL USA. [Berg, Alfred; Flum, David] Univ Washington, Seattle, WA 98195 USA. [Gabriel, Sherine] Mayo Clin, Rochester, MN USA. [Goodman, Steven N.; Ioannidis, John P. A.] Stanford Univ, Stanford, CA 94305 USA. [Helfand, Mark] Portland VA Med Ctr, Portland, OR USA. [Lauer, Michael] NHLBI, Bethesda, MD 20892 USA. [Meltzer, David] Univ Chicago, Chicago, IL 60637 USA. [Mittman, Brian] Dept Vet Affairs, Sepulveda, CA USA. [Newhouse, Robin] Univ Maryland, Baltimore, MD 21201 USA. [Normand, Sharon-Lise; Schneeweiss, Sebastian] Harvard Univ, Sch Med, Boston, MA USA. [Normand, Sharon-Lise] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Slutsky, Jean] Agcy Healthcare Res & Qual, Rockville, MD USA. [Tinetti, Mary] Yale Univ, New Haven, CT USA. [Yancy, Clyde] Northwestern Univ, Chicago, IL 60611 USA. RP Basch, E (reprint author), Mem Sloan Kettering Canc Ctr, Hlth Outcomes Res Grp, 307 63rd St, New York, NY 10463 USA. EM ebasch@mskcc.org RI Schneeweiss, Sebastian/C-2125-2013; Meltzer, David/C-2926-2009 OI Meltzer, David/0000-0003-2790-7393 FU PCORI of the Methodology Committee FX The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. All of the authors reported receiving funding from PCORI as members of the Methodology Committee, including compensation for travel and lodging for PCORI-related meetings as well as time spent providing service to the PCORI. NR 45 TC 96 Z9 96 U1 3 U2 26 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 18 PY 2012 VL 307 IS 15 BP 1636 EP 1640 DI 10.1001/jama.2012.466 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 927GU UT WOS:000302896100026 ER PT J AU Lindenhovius, ALC Doornberg, JN Brouwer, KM Jupiter, JB Mudgal, CS Ring, D AF Lindenhovius, Anneluuk L. C. Doornberg, Job N. Brouwer, Kim M. Jupiter, Jesse B. Mudgal, Chaitanya S. Ring, David TI A Prospective Randomized Controlled Trial of Dynamic Versus Static Progressive Elbow Splinting for Posttraumatic Elbow Stiffness SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID FLEXION CONTRACTURES; MOTION; SLINGS AB Background: Both dynamic and static progressive (turnbuckle) splints are used to help stretch a contracted elbow capsule to regain motion after elbow trauma. There are advocates of each method, but no comparative data. This prospective randomized controlled trial tested the null hypothesis that there is no difference in improvement of motion and Disabilities of the Arm, Shoulder and Hand (DASH) scores between static progressive and dynamic splinting. Methods: Sixty-six patients with posttraumatic elbow stiffness were enrolled in a prospective randomized trial: thirty-five in the static progressive and thirty-one in the dynamic cohort. Elbow function was measured at enrollment and at three, six, and twelve months later. Patients completed the DASH questionnaire at enrollment and at the six and twelve-month evaluation. Three patients asked to be switched to static progressive splinting. The analysis was done according to intention-to-treat principles and with use of mean imputation for missing data. Results: There were no significant differences in flexion arc at any time point. Improvement in the arc of flexion (dynamic versus static) averaged 29 degrees versus 28 degrees at three months (p = 0.87), 40 degrees versus 39 degrees at six months (p = 0.72), and 47 degrees versus 49 degrees at twelve months after splinting was initiated (p = 0.71). The average DASH score (dynamic versus static) was 50 versus 45 points at enrollment (p = 0.52), 32 versus 25 points at six months (p < 0.05), and 28 versus 26 points at twelve months after enrollment (p = 0.61). Conclusions: Posttraumatic elbow stiffness can improve with exercises and dynamic or static splinting over a period of six to twelve months, and patience is warranted. There were no significant differences in improvement in motion between static progressive and dynamic splinting protocols, and the choice of splinting method can be determined by the patients and their physicians. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. C1 [Lindenhovius, Anneluuk L. C.; Doornberg, Job N.; Brouwer, Kim M.; Jupiter, Jesse B.; Mudgal, Chaitanya S.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Lindenhovius, ALC (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Dept Orthopaed Surg, Yawkey Ctr Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 14 TC 17 Z9 20 U1 0 U2 6 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 APR 18 PY 2012 VL 94A IS 8 BP 694 EP 700 DI 10.2106/JBJS.J.01761 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 929TG UT WOS:000303088000004 PM 22517385 ER PT J AU Yao, YD Sun, TM Huang, SY Dou, S Lin, L Chen, JN Ruan, JB Mao, CQ Yu, FY Zeng, MS Zang, JY Liu, Q Su, FX Zhang, P Lieberman, J Wang, J Song, EW AF Yao, Yan-dan Sun, Tian-meng Huang, Song-yin Dou, Shuang Lin, Ling Chen, Jia-ning Ruan, Jian-bin Mao, Cheng-qiong Yu, Feng-yan Zeng, Mu-sheng Zang, Jian-ye Liu, Qiang Su, Feng-xi Zhang, Peter Lieberman, Judy Wang, Jun Song, Erwei TI Targeted Delivery of PLK1-siRNA by ScFv Suppresses Her2(+) Breast Cancer Growth and Metastasis SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID SMALL INTERFERING RNAS; POLO-LIKE KINASES; SIRNA DELIVERY; GENE; ACTIVATION; THERAPY; INHIBITION; RECEPTORS; SURVIVAL; CELLS AB A major obstacle to developing small interfering RNAs (siRNAs) as cancer drugs is their intracellular delivery to disseminated cancer cells. Fusion proteins of single-chain fragmented antibodies (ScFvs) and positively charged peptides deliver siRNAs into specific target cells. However, the therapeutic potential of ScFv-mediated siRNA delivery has not been evaluated in cancer. Here, we tested whether Polo-like kinase 1 (PLK1) siRNAs complexed with a Her2-ScFv-protamine peptide fusion protein (F5-P) could suppress Her2(+) breast cancer cell lines and primary human cancers in orthotopic breast cancer models. PLK1-siRNAs transferred by F5-P inhibited target gene expression, reduced proliferation, and induced apoptosis of Her2(+) breast cancer cell lines and primary human cancer cells in vitro without triggering an interferon response. Intravenously injected F5-P/PLK1-siRNA complexes concentrated in orthotopic Her2(+) breast cancer xenografts and persisted for at least 72 hours, leading to suppressed PLK1 gene expression and tumor cell apoptosis. The intravenously injected siRNA complexes retarded Her2(+) breast tumor growth, reduced metastasis, and prolonged survival without evident toxicity. F5-P-mediated delivery of a cocktail of PLK1, CCND1, and AKT siRNAs was more effective than an equivalent dose of PLK1-siRNAs alone. These data suggest that F5-P could be used to deliver siRNAs to treat Her2(+) breast cancer. C1 [Yao, Yan-dan; Huang, Song-yin; Lin, Ling; Chen, Jia-ning; Yu, Feng-yan; Liu, Qiang; Su, Feng-xi; Song, Erwei] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou 510120, Peoples R China. [Sun, Tian-meng; Dou, Shuang; Ruan, Jian-bin; Mao, Cheng-qiong; Zang, Jian-ye; Wang, Jun] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Peoples R China. [Sun, Tian-meng; Dou, Shuang; Ruan, Jian-bin; Mao, Cheng-qiong; Zang, Jian-ye; Wang, Jun] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Peoples R China. [Zeng, Mu-sheng] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol So China, Guangzhou 510060, Guangdong, Peoples R China. [Zhang, Peter] Shanghai GenePharma Co Ltd, Shanghai 201203, Peoples R China. [Lieberman, Judy] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. [Lieberman, Judy] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. EM lieberman@idi.harvard.edu; jwang699@ustc.edu.cn; songerwei02@yahoo.com.cn RI Wang, Jun/F-9033-2011; Zang, Jianye/E-5228-2013; Lieberman, Judy/A-2717-2015; Mao, Chengqiong/I-7570-2015 OI Wang, Jun/0000-0001-9957-9208; Mao, Chengqiong/0000-0002-3250-7733 FU National Basic Research Program of China (973 programs) [2010CB912800, 2010CB934000, 2009CB521706]; National Natural Science Foundation of China [30921140312, 30525022, 51125012, 30830110, 30772550, 20974105, 81172526]; Guangdong Natural Science Foundation [S2011040000385]; U.S. Department of Defense FX Supported by the National Basic Research Program of China (973 programs 2010CB912800, 2010CB934000, and 2009CB521706), National Natural Science Foundation of China grants (30921140312, 30525022, 51125012, 30830110, 30772550, 20974105, and 81172526), Guangdong Natural Science Foundation (S2011040000385), and U.S. Department of Defense Breast Cancer Research Program grant (J.L.). NR 35 TC 32 Z9 32 U1 2 U2 51 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 18 PY 2012 VL 4 IS 130 AR 130ra48 DI 10.1126/scitranslmed.3003601 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 929FE UT WOS:000303045900005 PM 22517885 ER PT J AU Bhatia, RS AF Bhatia, R. Sacha TI Alternative financing for health care: A path to sustainability? SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material C1 [Bhatia, R. Sacha] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Bhatia, R. Sacha] Harvard Univ, Sch Med, Boston, MA USA. RP Bhatia, RS (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM rsbhatia@partners.org NR 9 TC 0 Z9 0 U1 0 U2 3 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD APR 17 PY 2012 VL 184 IS 7 BP E337 EP E338 DI 10.1503/cmaj.110672 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 007RO UT WOS:000308906000001 PM 21859869 ER PT J AU Wei, G Margolin, AA Haery, L Brown, E Cucolo, L Julian, B Shehata, S Kung, AL Beroukhim, R Golub, TR AF Wei, Guo Margolin, Adam A. Haery, Leila Brown, Emily Cucolo, Lisa Julian, Bina Shehata, Shyemaa Kung, Andrew L. Beroukhim, Rameen Golub, Todd R. TI Chemical Genomics Identifies Small-Molecule MCL1 Repressors and BCL-xL as a Predictor of MCL1 Dependency SO CANCER CELL LA English DT Article ID BH3 MIMETIC ABT-737; IMMUNOHISTOCHEMICAL ANALYSIS; REGULATORY NETWORKS; FAMILY PROTEINS; BREAST-CANCER; UP-REGULATION; CELL-DEATH; APOPTOSIS; RESISTANCE; INHIBITOR AB MCL1, which encodes the antiapoptotic protein MCL1, is among the most frequently amplified genes in human cancer. A chemical genomic screen identified compounds, including anthracyclines, that decreased MCL1 expression. Genomic profiling indicated that these compounds were global transcriptional repressors that preferentially affect MCL1 due to its short mRNA half-life. Transcriptional repressors and MCL1 shRNAs induced apoptosis in the same cancer cell lines and could be rescued by physiological levels of ectopic MCL1 expression. Repression of MCL1 released the proapoptotic protein BAK from MCL1, and Bak deficiency conferred resistance to transcriptional repressors. A computational model, validated in vivo, indicated that high BCL-xL expression confers resistance to MCL1 repression, thereby identifying a patient-selection strategy for the clinical development of MCL1 inhibitors. C1 [Wei, Guo; Margolin, Adam A.; Haery, Leila; Brown, Emily; Cucolo, Lisa; Julian, Bina; Beroukhim, Rameen; Golub, Todd R.] Broad Inst Massachusetts Inst Technol & Harvard U, Canc Program, Cambridge, MA 02142 USA. [Wei, Guo; Kung, Andrew L.; Golub, Todd R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Shehata, Shyemaa; Beroukhim, Rameen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Golub, Todd R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Golub, TR (reprint author), Broad Inst Massachusetts Inst Technol & Harvard U, Canc Program, Cambridge, MA 02142 USA. EM golub@broadinstitute.org OI Kung, Andrew/0000-0002-9091-488X FU NIH [P01 CA068484, 5U54CA112962]; The Damon Runyon Cancer Research Foundation; Novartis Institutes of Biomedical Research FX This work was supported by NIH grant nos. P01 CA068484 and 5U54CA112962 (to T.R.G.). G.W. was supported by a postdoctoral fellowship from The Damon Runyon Cancer Research Foundation. R.B. was supported by a grant from the Novartis Institutes of Biomedical Research. The authors thank the Broad Institute Chemical Biology Platform for assistance in small-molecule screening; the Broad Institute Genetic Analysis Platform for Affymetrix microarray profiling; the Broad-Novartis Cancer Cell Line Encyclopedia Project for data sharing; Joshua Gould for assistance in data analysis; Jinyan Du, Xiaodong Lu, and Emily Gray for technical assistance; and Leslie Gaffney and Lauren Solomon for editorial assistance. NR 45 TC 59 Z9 59 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR 17 PY 2012 VL 21 IS 4 BP 547 EP 562 DI 10.1016/j.ccr.2012.02.028 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 931AW UT WOS:000303187400011 PM 22516262 ER PT J AU Zhang, B Ho, YW Huang, Q Maeda, T Lin, A Lee, SU Hair, A Holyoake, TL Huettner, C Bhatia, R AF Zhang, Bin Ho, Yin Wei Huang, Qin Maeda, Takahiro Lin, Allen Lee, Sung-uk Hair, Alan Holyoake, Tessa L. Huettner, Claudia Bhatia, Ravi TI Altered Microenvironmental Regulation of Leukemic and Normal Stem Cells in Chronic Myelogenous Leukemia SO CANCER CELL LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW; HEMATOPOIETIC STEM; MULTIPOTENT PROGENITORS; MALIGNANT PROGENITORS; NOD/SCID MICE; CHRONIC-PHASE; IN-VITRO; IMATINIB; CML AB We characterized leukemia stem cells (LSC) in chronic phase chronic myelogenous leukemia (CML) using a transgenic mouse model. LSC were restricted to cells with long-term hematopoietic stem cell (LTHSC) phenotype. CML LTHSC demonstrated reduced homing and retention in the bone marrow (BM), related to decreased CXCL12 expression in CML BM, resulting from increased G-CSF production by leukemia cells. Altered cytokine expression in CML BM was associated with selective impairment of normal LTHSC growth and a growth advantage to CML LTHSC. Imatinib (IM) treatment partially corrected abnormalities in cytokine levels and LTHSC growth. These results were validated using human CML samples and provide improved understanding of microenvironmental regulation of normal and leukemic LTHSC and their response to IM in CML. C1 [Zhang, Bin; Ho, Yin Wei; Maeda, Takahiro; Lin, Allen; Lee, Sung-uk; Bhatia, Ravi] City Hope Natl Med Ctr, Div Hematopoiet Stem Cell & Leukemia Res, Duarte, CA 91010 USA. [Huang, Qin] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA. [Hair, Alan; Holyoake, Tessa L.] Univ Glasgow, Inst Canc Sci, Coll Med Vet & Life Sci, Glasgow G61 1BD, Lanark, Scotland. [Huettner, Claudia] Dana Farber Canc Inst, Beffer Inst Appl Canc Sci, Boston, MA 02215 USA. RP Bhatia, R (reprint author), City Hope Natl Med Ctr, Div Hematopoiet Stem Cell & Leukemia Res, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM rbhatia@coh.org RI Holyoake, Tessa/M-3668-2015 OI Holyoake, Tessa/0000-0002-0608-6066 FU National Institutes of Health [R01 HL77847, R01 CA95684]; CR-UK [C11074/A11008]; Glasgow Experimental Cancer Medicine Centre (ECMC); Cancer Research UK; Chief Scientist's Office (Scotland) FX This work was supported by the National Institutes of Health grants (R01 HL77847 and R01 CA95684 to R.B.) and CR-UK grant (C11074/A11008 to T.H.). We acknowledge the excellent technical support of the COHNMC Analytical Cytometry core, the Clinical Immunobiology Correlative Studies laboratory, and the Animal Resources Center. Procurement of biospecimens was facilitated by the City of Hope Biospecimen Repository Protocol. This study was supported by the Glasgow Experimental Cancer Medicine Centre (ECMC), which is funded by Cancer Research UK and the Chief Scientist's Office (Scotland). NR 43 TC 112 Z9 116 U1 1 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR 17 PY 2012 VL 21 IS 4 BP 577 EP 592 DI 10.1016/j.ccr.2012.02.018 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 931AW UT WOS:000303187400013 PM 22516264 ER PT J AU Venkitachalam, L Wang, KJ Porath, A Corbalan, R Hirsch, AT Cohen, DJ Smith, SC Ohman, EM Steg, PG Bhatt, DL Magnuson, EA AF Venkitachalam, Lakshmi Wang, Kaijun Porath, Avi Corbalan, Ramon Hirsch, Alan T. Cohen, David J. Smith, Sidney C., Jr. Ohman, E. Magnus Steg, Ph Gabriel Bhatt, Deepak L. Magnuson, Elizabeth A. CA REACH Registry Investigators TI Global Variation in the Prevalence of Elevated Cholesterol in Outpatients With Established Vascular Disease or 3 Cardiovascular Risk Factors According to National Indices of Economic Development and Health System Performance SO CIRCULATION LA English DT Article DE cardiovascular disease; hypercholesterolemia; global trends; health system performance; national health expenditures ID PREVENTION GUIDELINES; MYOCARDIAL-INFARCTION; EUROPEAN COUNTRIES; INCOME COUNTRIES; EUROASPIRE-II; MIDDLE-INCOME; EVENT RATES; ATHEROTHROMBOSIS; AFFORDABILITY; AVAILABILITY AB Background-Elevated serum cholesterol accounts for a considerable proportion of cardiovascular disease worldwide. An understanding of the relationship between country-level economic and health system factors and elevated cholesterol may provide insight for prioritization of cardiovascular prevention programs. Methods and Results-Using hierarchical models, we examined the relationship between elevated total cholesterol (>200 mg/dL) in 53 570 outpatients from 36 countries, and tertiles of several country-level indices: (1) gross national income, (2) total expenditure on health as percentage of gross domestic product, (3) government expenditure on health as percentage of total expenditure on health, (4) out-of-pocket expenditures as percentage of private expenditure on health, and the World Health Organization indices of (5) Health System Achievement and (6) Performance/Efficiency. Overall, 38% of outpatients had total cholesterol >200 mg/dL (>5.18 mmol/L), and 9.3% of the total variability in elevated cholesterol was at the country level; this proportion was higher for patients with (12.1%) versus without (7.4%) history of hyperlipidemia. Among patients with history of hyperlipidemia, countries in the highest tertile of gross national income or World Health Organization Health System Achievement had lower odds of elevated cholesterol than lower tertiles (P<0.001, for both). Countries in the highest tertile of out-of-pocket health expenditures had higher odds of elevated cholesterol than those in the lowest tertile (P<0.001). No significant associations were found for patients without history of hyperlipidemia. Conclusions-Global variations in the prevalence of elevated cholesterol among patients with history of hyperlipidemia are associated with country-level economic development and health system indices. These results support the need for strengthening efforts toward effective cardiovascular disease prevention and control and may provide insight for health policy setting at the national level. (Circulation. 2012; 125: 1858-1869.) C1 [Wang, Kaijun; Cohen, David J.; Magnuson, Elizabeth A.] St Lukes Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Venkitachalam, Lakshmi; Cohen, David J.; Magnuson, Elizabeth A.] Univ Missouri, Kansas City Sch Med, Kansas City, MO 64110 USA. [Porath, Avi] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. [Corbalan, Ramon] Pontificia Univ Catolica Chile, Div Cardiovasc, Santiago, Chile. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Ohman, E. Magnus] Duke Univ, Med Ctr, Div Cardiovasc Med, Durham, NC USA. [Steg, Ph Gabriel] Univ Paris Diderot, Hop Bichat, Assistance Publ Hop Paris, INSERM U 698, F-75877 Paris, France. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Magnuson, Elizabeth A.] Harvard Univ, Sch Med, Boston, MA USA. RP Magnuson, EA (reprint author), St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM emagnuson@saint-lukes.org OI Venkitachalam, Lakshmi/0000-0003-0703-3932 FU Sanofi-Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); American Heart Association; Saint-Luke's Mid America Heart Institute; Boston Scientific; Abbott Vascular; Edwards Lifesciences; Merck/Schering Plough; Daiichi-Sankyo; St. Jude medical; Astra Zeneca; Bristol-Myers Squibb/Sanofi Aventis; CV Therapeutics; Daiichi Sankyo; Datascope; Eli Lilly; Marquet; Schering-Plough; Medicines Company; Abiomed; Gilead Sciences; Liposcience; Northpoint Domain; Pozen; Response Biomedical; WebMD; Servier; Amarin; Eisai; Ethicon; Medtronic FX The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The REACH Registry is endorsed by the World Heart Federation. Dr Venkitachalam was supported by the American Heart Association Pharmaceutical Roundtable-David and Stevie Spina Outcomes Research Postdoctoral Fellowship at the Saint-Luke's Mid America Heart Institute.; Dr Cohen received research grant support (significant) from Boston Scientific, Abbott Vascular, Edwards Lifesciences, Merck/Schering Plough, Daiichi-Sankyo, St. Jude medical, and Astra Zeneca. He received consulting income (modest) from Medtronic and speaking honoraria (modest) from Eli Lilly/Daiichi-Sankyo. Dr Hirsch received consulting fees (modest) from Bristol-Myers Squibb/Sanofi Aventis partnership, and honorarium (modest) from Bristol-Myers Squibb/Sanofi Aventis partnership. Dr Ohman received research grants (significant) from Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo, Datascope, Eli Lilly, Marquet, Sanofi-Aventis, Schering-Plough, and The Medicines Company; and received fees for consulting or other services (modest) for Abiomed, AstraZeneca, CV Therapeutics, Datascope, Gilead Sciences, Liposcience, Marquet, Northpoint Domain, Pozen, Response Biomedical, Sanofi-Aventis, The Medicines Company, and WebMD (theheart.org). Dr Steg received research grants (significant to his institution) from Servier; he was a member of consultancy or advisory boards (modest) for Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, Daiichi-Sankyo-Lilly, GlaxoSmithKline, Medtronic, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier, and The Medicines Company; and he is a stockholder in Aterovax. Dr Bhatt received research grants (significant) from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company. Dr Magnuson received research grants (significant) and honoraria (modest) from Sanofi-Aventis/Bristol-Myers Squibb partnership, and research grants (significant) from Eli Lilly, Astra Zeneca, and Daiichi-Sankyo. Drs Venkitachalam, Wang, Porath, Corbalan, and Smith had no disclosures. NR 37 TC 8 Z9 11 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 APR 17 PY 2012 VL 125 IS 15 BP 1858 EP + DI 10.1161/CIRCULATIONAHA.111.064378 PG 23 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 928CM UT WOS:000302957800013 PM 22492667 ER PT J AU Shah, AM Yu, M Nakamura, Z Ciciliano, J Ulman, M Kotz, K Stott, SL Maheswaran, S Haber, DA Toner, M AF Shah, Ajay M. Yu, Min Nakamura, Zev Ciciliano, Jordan Ulman, Matthew Kotz, Kenneth Stott, Shannon L. Maheswaran, Shyamala Haber, Daniel A. Toner, Mehmet TI Biopolymer System for Cell Recovery from Microfluidic Cell Capture Devices SO ANALYTICAL CHEMISTRY LA English DT Article ID CIRCULATING TUMOR-CELLS; RGD NANOPATTERNED HYDROGELS; ALGINATE HYDROGELS; PROSTATE-CANCER; WHOLE-BLOOD; ENUMERATION AB Microfluidic systems for affinity-based cell isolation have emerged as a promising approach for the isolation of specific cells from complex matrices (i.e., circulating tumor cells in whole blood). However, these technologies remain limited by the lack of reliable methods for the innocuous recovery of surface captured cells. Here, we present a biofunctional sacrificial hydrogel coating for microfluidic chips that enables the highly efficient release of isolated cells (99% +/- 1%) following gel dissolution. This covalently cross-linked alginate biopolymer system is stable in a wide variety of physiologic solutions (including EDTA treated whole blood) and may be rapidly degraded via backbone cleavage with alginate lyase. The capture and release of EpCAM expressing cancer cells using this approach was found to have no significant effect on cell viability or proliferative potential, and recovered cells were demonstrated to be compatible with downstream immunostaining and FISH analysis. C1 [Shah, Ajay M.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Yu, Min; Nakamura, Zev; Ciciliano, Jordan; Ulman, Matthew; Maheswaran, Shyamala; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Shah, Ajay M.; Kotz, Kenneth; Stott, Shannon L.; Toner, Mehmet] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Haber, Daniel A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kotz, Kenneth; Stott, Shannon L.; Maheswaran, Shyamala; Toner, Mehmet] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Yu, Min; Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Kotz, Kenneth; Stott, Shannon L.; Toner, Mehmet] Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Toner, M (reprint author), 114 16th St, Charlestown, MA 02129 USA. EM mtoner@hms.harvard.edu FU Dream Team from the Prostate Cancer Foundation; National Institute for Biomedical Imaging and Bioengineering (NIBIB); DOD PCRP FX The authors thank Octavio Hurtado and Laura Libby for expert technical support and Dr. Sangeeta Bhatia for insightful conversations. This work was supported by Dream Team awards from the Prostate Cancer Foundation and Stand Up to Cancer (to D.A.H. and M.T.) and a Quantum Grant from the National Institute for Biomedical Imaging and Bioengineering (NIBIB) to M.T. A.M.S. is supported by a DOD PCRP predoctoral fellowship. NR 35 TC 45 Z9 46 U1 6 U2 80 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD APR 17 PY 2012 VL 84 IS 8 BP 3682 EP 3688 DI 10.1021/ac300190j PG 7 WC Chemistry, Analytical SC Chemistry GA 926NQ UT WOS:000302838500030 PM 22414137 ER PT J AU Wang, PG Fisher, D Rao, A Giese, RW AF Wang, Poguang Fisher, David Rao, Anjana Giese, Roger W. TI Nontargeted Nucleotide Analysis Based on Benzoylhistamine Labeling-MALDI-TOF/TOF-MS: Discovery of Putative 6-Oxo-Thymine in DNA SO ANALYTICAL CHEMISTRY LA English DT Article ID ADDUCT FORMATION; THYMINE; 5-METHYLCYTOSINE; STANDARDIZATION; GLYCOSYLASE; EXPOSURE; GLYCOL; ASSAY AB A method for nontargeted analysis of modified nucleotides in DNA (and RNA) is reported based on labeling with benzoylhistamine (BH) followed by MALDI-MS. The method provides deoxynucleotide-specific detection, accurate measurement of molecular ions, high sensitivity, semiquantitation, and, to the extent studied to date, normalization of response within a factor of <3. C1 [Wang, Poguang; Giese, Roger W.] Northeastern Univ, Pharmaceut Sci & Barnett Inst, Boston, MA 02115 USA. [Fisher, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Rao, Anjana] La Jolla Inst Allergy & Immunol, La Jolla, CA 92307 USA. RP Giese, RW (reprint author), Northeastern Univ, Pharmaceut Sci & Barnett Inst, 122 MU,360 Huntington Ave, Boston, MA 02115 USA. EM r.giese@neu.edu FU NIH from NIEHS [P42ES017198]; NIH (via Massachusetts General Hospital, Harvard Medical School) [AR043369]; NIH [AI44432, HD065812] FX This work was supported by NIH Grant P42ES017198 from NIEHS, NIH Grant AR043369 (via Massachusetts General Hospital, Harvard Medical School), NIH Grant AI44432, and NIH Grant HD065812. The authors thank Jean Cadet for reviewing this manuscript. This is a contribution 1010 from the Barnett Institute. NR 24 TC 12 Z9 12 U1 2 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD APR 17 PY 2012 VL 84 IS 8 BP 3811 EP 3819 DI 10.1021/ac300532z PG 9 WC Chemistry, Analytical SC Chemistry GA 926NQ UT WOS:000302838500048 PM 22409256 ER PT J AU Cohen, SP White, RL Kurihara, C Larkin, TM Chang, A Griffith, SR Gilligan, C Larkin, R Morlando, B Pasquina, PF Yaksh, TL Nguyen, C AF Cohen, Steven P. White, Ronald L. Kurihara, Connie Larkin, Thomas M. Chang, Audrey Griffith, Scott R. Gilligan, Christopher Larkin, Ralph Morlando, Benny Pasquina, Paul F. Yaksh, Tony L. Nguyen, Conner TI Epidural Steroids, Etanercept, or Saline in Subacute Sciatica A Multicenter, Randomized Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID LOW-BACK-PAIN; NECROSIS-FACTOR-ALPHA; LUMBAR DISC HERNIATION; CORTICOSTEROID INJECTIONS; DOUBLE-BLIND; NUCLEUS PULPOSUS; TRANSFORAMINAL INJECTION; EQUIVALENCE TRIAL; NEUROPATHIC PAIN; SPINAL STENOSIS AB Background: Perineural inhibitors of tumor necrosis factor have recently generated intense interest as an alternative to epidural steroid injections for lumbosacral radiculopathy. Objective: To evaluate whether epidural steroids, etanercept, or saline better improves pain and function in adults with lumbosacral radiculopathy. Design: A multicenter, 3-group, randomized, placebo-controlled trial conducted from 2008 to 2011. Randomization was computer-generated and stratified by site. Pharmacists prepared the syringes. Patients, treating physicians, and nurses assessing outcomes were blinded to treatment assignment. (ClinicalTrials.gov registration number: NCT00733096) Setting: Military and civilian treatment centers. Patients: 84 adults with lumbosacral radiculopathy of less than 6 months' duration. Intervention: 2 epidural injections of steroids, etanercept, or saline, mixed with bupivacaine and separated by 2 weeks. Measurements: The primary outcome measure was leg pain 1 month after the second injection. All patients had 1-month follow-up visits; patients whose condition improved remained blinded for the 6-month study period. Results: The group that received epidural steroids had greater reductions in the primary outcome measure than those who received saline (mean difference, -1.26 [95% CI, -2.79 to 0.27]; P = 0.11) or etanercept (mean difference, -1.01 [CI, -2.60 to 0.58]; P = 0.21). For back pain, smaller differences favoring steroids compared with saline (mean difference, -0.52 [CI, -1.85 to 0.81]; P = 0.44) and etanercept (mean difference, -0.92 [CI, -2.28 to 0.44]; P = 0.18) were observed. The largest differences were noted for functional capacity, in which etanercept fared worse than the other treatments: steroids vs. etanercept (mean difference, -16.16 [CI, -26.05 to -6.27]; P = 0.002), steroids vs. saline (mean difference, -5.87 [CI, -15.59 to 3.85]; P = 0.23), and etanercept vs. saline (mean difference, 10.29 [CI, 0.55 to 20.04]; P = 0.04). More patients treated with epidural steroids (75%) reported 50% or greater leg pain relief and a positive global perceived effect at 1 month than those who received saline (50%) or etanercept (42%) (P = 0.09). Limitation: Short-term follow-up, small sample size, and a possibly subtherapeutic dose of etanercept. Conclusion: Epidural steroid injections may provide modest short-term pain relief for some adults with lumbosacral radiculopathy, but larger studies with longer follow-up are needed to confirm their benefits. C1 Johns Hopkins Sch Med, Baltimore, MD USA. Landstuhl Reg Med Ctr, Landstuhl, Germany. Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. Pkwy Neurosci & Spine Inst, Hagerstown, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. CUNY John Jay Coll Criminal Justice, New York, NY 10019 USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Cohen, SP (reprint author), 550 N Broadway,Suite 301, Baltimore, MD 21029 USA. EM scohen40@jhmi.edu FU John P. Murtha Neuroscience and Pain Institute; International Spinal Intervention Society; Center for Rehabilitation Sciences Research FX The John P. Murtha Neuroscience and Pain Institute, International Spinal Intervention Society, and Center for Rehabilitation Sciences Research. NR 62 TC 62 Z9 63 U1 5 U2 7 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 17 PY 2012 VL 156 IS 8 BP 551 EP U154 DI 10.7326/0003-4819-156-8-201204170-00002 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 930PO UT WOS:000303151800014 PM 22508732 ER PT J AU Ganz, PA Barry, JM Burke, W Col, NF Corso, PS Dodson, E Hammond, E Kogan, BA Lynch, CF Newcomer, L Seifter, EJ Tooze, JA Viswanath, K Wessells, H AF Ganz, Patricia A. Barry, John M. Burke, Wylie Col, Nananda F. Corso, Phaedra S. Dodson, Everett Hammond, Elizabeth Kogan, Barry A. Lynch, Charles F. Newcomer, Lee Seifter, Eric J. Tooze, Janet A. Viswanath, Kasisomayajula Wessells, Hunter TI National Institutes of Health State-of-the-Science Conference: Role of Active Surveillance in the Management of Men With Localized Prostate Cancer SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Washington, Sch Med, Seattle, WA USA. Univ New England, Biddeford, ME USA. Shared Decis Making Resources, Georgetown, ME USA. Univ Georgia, Athens, GA 30602 USA. Lombardi Comprehens Canc Ctr, Washington, DC USA. Georgetown Univ Hosp, Washington, DC 20007 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Amir Sys, Salt Lake City, UT USA. Albany Med Coll, Albany, NY 12208 USA. Urol Inst NE New York, Albany, NY USA. Univ Iowa, Iowa City, IA USA. United Healthcare, Minneapolis, MN USA. Johns Hopkins Univ, Sch Med, Lutherville Timonium, MD USA. Sidney Kimmel Comprehens Canc Ctr, Lutherville Timonium, MD USA. Wake Forest Sch Med, Winston Salem, NC USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ganz, PA (reprint author), Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. FU NCI NIH HHS [P30 CA012197] NR 0 TC 108 Z9 110 U1 0 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 17 PY 2012 VL 156 IS 8 BP 591 EP U118 DI 10.7326/0003-4819-156-8-201204170-00010 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 930PO UT WOS:000303151800018 PM 22351514 ER PT J AU Grant, RW Hong, CS Atlas, SJ AF Grant, Richard W. Hong, Clemens S. Atlas, Steven J. TI Defining Patient Complexity RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Grant, Richard W.] Kaiser Permanente No Calif, Oakland, CA 94612 USA. [Hong, Clemens S.; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Grant, RW (reprint author), Kaiser Permanente No Calif, Oakland, CA 94612 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 17 PY 2012 VL 156 IS 8 BP 607 EP 607 DI 10.7326/0003-4819-156-8-201204170-00015 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 930PO UT WOS:000303151800025 ER PT J AU Prochazka, AV Caverly, TJ AF Prochazka, Allan V. Caverly, Tanner J. TI Radical prostatectomy and watchful waiting for localized prostate cancer did not differ for quality of life SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Prochazka, Allan V.] Denver VAMC, Denver, CO USA. Univ Colorado, Denver Sch Med, Denver, CO 80202 USA. RP Prochazka, AV (reprint author), Denver VAMC, Denver, CO USA. NR 2 TC 0 Z9 0 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 17 PY 2012 VL 156 IS 8 AR JC4-3 DI 10.7326/0003-4819-156-8-201204170-02003 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 930PO UT WOS:000303151800002 PM 22508743 ER PT J AU Wang, LH Lin, F Wang, J Wu, JC Han, R Zhu, LJ DiFiglia, M Qin, ZH AF Wang, Linhui Lin, Fang Wang, Jin Wu, Junchao Han, Rong Zhu, Lujia DiFiglia, Marian Qin, Zhenghong TI Expression of mutant N-terminal huntingtin fragment (htt552-100Q) in astrocytes suppresses the secretion of BDNF SO BRAIN RESEARCH LA English DT Article DE Astrocytes; Huntington's disease; Brain-derived neurotrophic factor; Huntingtin; Secretion ID STRIATAL PROJECTION NEURONS; POST-GOLGI TRAFFICKING; NEUROTROPHIC FACTOR; INTRACELLULAR TRAFFICKING; GLIAL-CELLS; RAT-BRAIN; INTRANUCLEAR INCLUSIONS; HIPPOCAMPAL-NEURONS; SIGNAL-TRANSDUCTION; PARKINSONS-DISEASE AB Huntington's disease (HD) is an inheritable neurological disorder caused by an abnormal expansion of the polyglutamine tract in the N-terminus of the protein huntingtin (htt). Mutant htt (mhtt) leads to selective neurodegeneration that preferentially affects striatal medium spiny neurons. Although mhtt is also expressed in astrocytes, whether and how astrocyte derived mhtt contributes to the neurodegeneration in HD remains largely unknown. In this study, a glia HD model, using an adenoviral vector to express wild-type and mutant N-terminal huntingtin fragment 1-552 aa (htt552) in rat primary cortical astrocytes, was generated. The influence of htt552 on the protein level of brain-derived neurotrophic factor (BDNF) in astrocytes was evaluated. Immunofluorescence showed that htt552-100Q formed aggregates in some astrocytes. These mhtt aggregates sequestered clathrin immunoreactivities and dispersed the Golgi complex. ELISA and immunofluorescence demonstrated an increase in BDNF levels in the astrocytes expressing htt552-100Q. Western blot analysis showed that there was an increase in pro-BDNF, but a decrease in mature BDNF in the astrocytes expressing htt552-100Q. Furthermore, medium collected from astrocytes expressing htt552-100Q showed a lower level of mature BDNF and less activity in supporting neurite development of primary cortical neurons. These results suggest that aggregates formed by mutant htt552 affect processing and secretion of the BDNF in astrocytes, which might contribute to the neuronal dysfunction and degeneration in HD. (C) 2012 Elsevier B.V. All rights reserved. C1 [Wang, Linhui; Lin, Fang; Wang, Jin; Wu, Junchao; Han, Rong; Zhu, Lujia; Qin, Zhenghong] Soochow Univ, Sch Pharm, Dept Pharmacol, Suzhou 215123, Peoples R China. [Wang, Linhui; Lin, Fang; Wang, Jin; Wu, Junchao; Han, Rong; Zhu, Lujia; Qin, Zhenghong] Soochow Univ, Sch Pharm, Lab Aging & Nervous Dis, Suzhou 215123, Peoples R China. [DiFiglia, Marian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurobiol Lab, Boston, MA 02129 USA. RP Qin, ZH (reprint author), Soochow Univ, Sch Pharm, Dept Pharmacol, Suzhou 215123, Peoples R China. EM zhqin5@hotmail.com FU National Nature Science Foundation of China [30900464, 30600197] FX This work was supported by grants from the National Nature Science Foundation of China nos. 30900464 and 30600197. NR 65 TC 10 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 17 PY 2012 VL 1449 BP 69 EP 82 DI 10.1016/j.brainres.2012.01.077 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 929WV UT WOS:000303097300007 PM 22410294 ER PT J AU Giang, E Dorner, M Prentoe, JC Dreux, M Evans, MJ Bukh, J Rice, CM Ploss, A Burton, DR Law, M AF Giang, Erick Dorner, Marcus Prentoe, Jannick C. Dreux, Marlene Evans, Matthew J. Bukh, Jens Rice, Charles M. Ploss, Alexander Burton, Dennis R. Law, Mansun TI Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cross-neutralizing antibody; antigenic determinant; protective determinant; chronic viral infection; virus challenge ID HUMAN MONOCLONAL-ANTIBODIES; CELL-CULTURE SYSTEMS; E2 GLYCOPROTEIN; E1 GLYCOPROTEIN; INFECTION; EPITOPE; STRATEGY; VACCINES; REVEALS; DESIGN AB Hepatitis C virus (HCV) infects similar to 2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human mAbs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies to HCV. C1 [Giang, Erick; Dreux, Marlene; Burton, Dennis R.; Law, Mansun] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Dorner, Marcus; Rice, Charles M.; Ploss, Alexander] Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, New York, NY 10065 USA. [Prentoe, Jannick C.; Bukh, Jens] Copenhagen Univ Hosp, Copenhagen Hepatitis Program C, Dept Infect Dis, DK-2650 Hvidovre, Denmark. [Prentoe, Jannick C.; Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark. [Prentoe, Jannick C.; Bukh, Jens] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, DK-2200 Copenhagen, Denmark. [Evans, Matthew J.] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. [Burton, Dennis R.] Harvard Univ, Boston, MA 02129 USA. [Burton, Dennis R.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02129 USA. RP Law, M (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM mlaw@scripps.edu RI Dreux, Marlene/M-7295-2014; OI Dreux, Marlene/0000-0002-6607-4796; Evans, Matthew/0000-0002-4991-3877; Dorner, Marcus/0000-0003-0321-4226; Prentoe, Jannick/0000-0003-2203-9478 FU National Institutes of Health [R21AI080916, R01AI079031, R01AI071084, RC1DK087193, R01AI072613, R01AI079043]; Starr Foundation; Greenberg Medical Institute; Center for Translational Science Award [UL1 RR024143]; Lundbeck Foundation; German Research Foundation (Deutsche Forschungsgesellschaft) FX We thank Travis Nieusma, Arthur Kim, Justin Robbins, Joshua Horwitz, and Marion Sourisseau for laboratory support; Christina Corbaci for graphics support; Frank Chisari for advice and encouragement; Takashi Wakita, Jonathan Ball, and Francois-Loic Cosset for HCVcc and HCVpp reagents; and Harry Greenberg, Jean Dubuisson, Jane McKeating, Steven Foung, and Arvind Patel for antibody reagents. Support for this work was provided by National Institutes of Health Grants R21AI080916 and R01AI079031 (to M. L.), R01AI071084 (to D. R. B.), RC1DK087193 (to C. M. R. and A. P.), R01AI072613 (to C. M. R.), and R01AI079043 (to Frank Chisari that supported M. Dreux); The Starr Foundation (C. M. R.); the Greenberg Medical Institute (C. M. R.); a Center for Translational Science Award (to A. P., under parent Grant UL1 RR024143 to The Rockefeller University); and The Lundbeck Foundation (J.B.). M. Dorner was supported by a postdoctoral fellowship from the German Research Foundation (Deutsche Forschungsgesellschaft). This is The Scripps Research Institute (TSRI) manuscript number 21335. NR 48 TC 121 Z9 122 U1 1 U2 23 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 APR 17 PY 2012 VL 109 IS 16 BP 6205 EP 6210 DI 10.1073/pnas.1114927109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 931UZ UT WOS:000303246100062 PM 22492964 ER PT J AU Barczak, AK Gomez, JE Kaufmann, BB Hinson, ER Cosimi, L Borowsky, ML Onderdonk, AB Stanley, SA Kaur, D Bryant, KF Knipe, DM Sloutsky, A Hung, DT AF Barczak, Amy K. Gomez, James E. Kaufmann, Benjamin B. Hinson, Ella R. Cosimi, Lisa Borowsky, Mark L. Onderdonk, Andrew B. Stanley, Sarah A. Kaur, Devinder Bryant, Kevin F. Knipe, David M. Sloutsky, Alexander Hung, Deborah T. TI RNA signatures allow rapid identification of pathogens and antibiotic susceptibilities SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antibiotic resistance; genomics; tuberculosis ID RESISTANT STAPHYLOCOCCUS-AUREUS; MYCOBACTERIUM-TUBERCULOSIS; MOLECULAR-DETECTION; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; INFECTIOUS-DISEASES; DIAGNOSTICS; ASSAY; GENE; MECHANISMS AB With rising rates of drug-resistant infections, there is a need for diagnostic methods that rapidly can detect the presence of pathogens and reveal their susceptibility to antibiotics. Here we propose an approach to diagnosing the presence and drug-susceptibility of infectious diseases based on direct detection of RNA from clinical samples. We demonstrate that species-specific RNA signatures can be used to identify a broad spectrum of infectious agents, including bacteria, viruses, yeast, and parasites. Moreover, we show that the behavior of a small set of bacterial transcripts after a brief antibiotic pulse can rapidly differentiate drug-susceptible and -resistant organisms and that these measurements can be made directly from clinical materials. Thus, transcriptional signatures could form the basis of a uniform diagnostic platform applicable across a broad range of infectious agents. C1 [Barczak, Amy K.; Gomez, James E.; Kaufmann, Benjamin B.; Hinson, Ella R.; Cosimi, Lisa; Stanley, Sarah A.; Hung, Deborah T.] Broad Inst, Cambridge, MA 02142 USA. [Barczak, Amy K.; Kaufmann, Benjamin B.; Hinson, Ella R.; Borowsky, Mark L.; Stanley, Sarah A.; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Barczak, Amy K.; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Barczak, Amy K.; Gomez, James E.; Kaufmann, Benjamin B.; Hinson, Ella R.; Stanley, Sarah A.; Bryant, Kevin F.; Knipe, David M.; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Cosimi, Lisa; Hung, Deborah T.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Onderdonk, Andrew B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kaur, Devinder; Sloutsky, Alexander] Univ Massachusetts, Sch Med, Massachusetts Supranatl TB Reference Lab, Jamaica Plain, MA 02130 USA. RP Hung, DT (reprint author), Broad Inst, Cambridge, MA 02142 USA. EM hung@molbio.mgh.harvard.edu FU National Institutes of Health (NIH) [U54 AI057159, AI 063106]; Parker B. Francis Foundation; NIH [K08 AI080944]; Helen Hay Whitney Fellowship; National Research Service [AI 081477] FX We thank Nathan Hasely for helpful discussions regarding analysis of the data, Marci DeGrace and Nir Hacohen (Massachusetts General Hospital) for the gift of the influenza samples, and Monica Diez and Subra Suresh (Massachusetts Institute of Technology) for the gift of the Plasmodium falciparum samples. This work was funded by National Institutes of Health (NIH) Grants U54 AI057159 (to D. T. H.), and AI 063106 (to D. M. K.). A. K. B. was supported by a Parker B. Francis Foundation Fellowship and NIH Grant K08 AI080944. S. A. S. was supported by a Helen Hay Whitney Fellowship. K. F. B. was supported by National Research Service Award Fellowship AI 081477. NR 30 TC 24 Z9 24 U1 1 U2 26 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 APR 17 PY 2012 VL 109 IS 16 BP 6217 EP 6222 DI 10.1073/pnas.1119540109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 931UZ UT WOS:000303246100064 PM 22474362 ER PT J AU Tan, Y Li, XK Prabhu, SD Brittian, KR Chen, Q Yin, X McClain, CJ Zhou, ZX Cai, L AF Tan, Yi Li, Xiaokun Prabhu, Sumanth D. Brittian, Kenneth R. Chen, Qiang Yin, Xia McClain, Craig J. Zhou, Zhanxiang Cai, Lu TI Angiotensin II Plays a Critical Role in Alcohol-Induced Cardiac Nitrative Damage, Cell Death, Remodeling, and Cardiomyopathy in a Protein Kinase C/Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Dependent Manner SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE alcoholic cardiomyopathy; angiotensin II; cardiac cell death; losartan; oxidative and nitrative stress; protein kinase C ID CHRONIC ETHANOL INGESTION; OXIDATIVE STRESS; DIABETIC CARDIOMYOPATHY; PKC-EPSILON; HEART; APOPTOSIS; EXPRESSION; RENIN; PEROXYNITRITE; PREVENTION AB Objectives The purpose of this study was to examine the cellular and molecular mechanisms underlying alcoholic cardiomyopathy. Background The mechanism for alcoholic cardiomyopathy remains largely unknown. Methods The chronic cardiac effects of alcohol were examined in mice feeding with alcohol or isocaloric control diet for 2 months. Signaling pathways of alcohol-induced cardiac cell death were examined in H9c2 cells. Results Compared with controls, hearts from alcohol-fed mice exhibited increased apoptosis, along with significant nitrative damage, demonstrated by 3-nitrotyrosine abundance. Alcohol exposure to H9c2 cells induced apoptosis, accompanied by 3-nitrotyrosine accumulation and nicotinamide adenine dinucleotide phosphate oxidase (NOX) activation. Pre-incubation of H9c2 cells with urate (peroxynitrite scavenger), N-G-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor), manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (a superoxide dismutase mimetic), and apocynin (NOX inhibitor) abrogated alcohol-induced apoptosis. Furthermore, alcohol exposure significantly increased the expression of angiotensin II and its type 1 receptor (AT1). A protein kinase C (PKC)-alpha/beta 1 inhibitor or PKC-beta 1 small interfering RNA and an AT1 blocker prevented alcohol-induced activation of NOX, and the AT1 blocker losartan significantly inhibited the expression of PKC-beta 1, indicating that alcohol-induced activation of NOX is mediated by PKC-beta 1 via AT1. To define the role of AT1-mediated PKC/NOX-derived superoxide generation in alcohol-induced cardiotoxicity, mice with knockout of the AT1 gene and wild-type mice were simultaneously treated with alcohol for 2 months. The knockout AT1 gene completely prevented cardiac nitrative damage, cell death, remodeling, and dysfunction. More importantly, pharmacological treatment of alcoholic mice with superoxide dismutase mimetic also significantly prevented cardiac nitrative damage, cell death, and remodeling. Conclusions Alcohol-induced nitrative stress and apoptosis, which are mediated by angiotensin II interaction with AT1 and subsequent activation of a PKC-beta 1-dependent NOX pathway, are a causal factor in the development of alcoholic cardiomyopathy. (J Am Coll Cardiol 2012;59:1477-86) (C) 2012 by the American College of Cardiology Foundation C1 [Tan, Yi; Li, Xiaokun; Cai, Lu] Wenzhou Med Coll, Chinese Amer Res Inst Diabet Complicat, Wenzhou, Peoples R China. [Tan, Yi; Chen, Qiang; Yin, Xia; Cai, Lu] Univ Louisville, Kosair Childrens Hosp Res Inst, Dept Pediat, Louisville, KY 40202 USA. [Prabhu, Sumanth D.] Univ Alabama, Dept Med Cardiovasc Dis, Birmingham, AL USA. [Prabhu, Sumanth D.] Birmingham VA Med Ctr, Birmingham, AL USA. [McClain, Craig J.; Cai, Lu] Univ Louisville, Dept Med, Robley Rex Vet Affairs Med Ctr, Louisville, KY 40202 USA. [McClain, Craig J.; Cai, Lu] Univ Louisville, Dept Pharmacol & Toxicol, Robley Rex Vet Affairs Med Ctr, Louisville, KY 40202 USA. [Zhou, Zhanxiang] Univ N Carolina, Dept Nutr, Greensboro, NC 27412 USA. RP Cai, L (reprint author), Univ Louisville, Dept Pediat, 570 S Preston St,Baxter 1,Suite 304F, Louisville, KY 40202 USA. EM 10cai001@louisville.edu FU American Diabetes Association [1-11-BS-17]; Zhejiang Province; Wenzhou Medical College; National Institutes of Health [R01AA014623, HL099014, HL078825, R37AA010762, P01AA017103]; Department of Veterans Affairs FX Supported, in part, by grants from the American Diabetes Association (1-11-BS-17 to Dr. Cai), Zhejiang Province (Extremely Key Subject Building Project "Pharmacology and Biochemical Pharmaceutics 2009") and Wenzhou Medical College (Starting-Up Fund for Chinese-American Research Institute for Diabetic Complications to Drs. Cai and Li), National Institutes of Health (R01AA014623 to Dr. Zhou, HL099014 and HL078825 to Dr. Prabhu, R37AA010762 and P01AA017103 to Dr. McClain), and the Department of Veterans Affairs (to Drs. Prabhu and McClain). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 25 TC 32 Z9 33 U1 0 U2 10 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 APR 17 PY 2012 VL 59 IS 16 BP 1477 EP 1486 DI 10.1016/j.jacc.2011.12.034 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 925TW UT WOS:000302785500010 PM 22497828 ER PT J AU Sorensen, G Gupta, PC Nagler, E Viswanath, K AF Sorensen, Glorian Gupta, Prakash C. Nagler, Eve Viswanath, Kasisomayajula TI Promoting Life Skills and Preventing Tobacco Use among Low-Income Mumbai Youth: Effects of Salaam Bombay Foundation Intervention SO PLOS ONE LA English DT Article ID HIGH-SCHOOL-STUDENTS; SMOKING PREVENTION; DISSEMINATION RESEARCH; CIGARETTE-SMOKING; RANDOMIZED-TRIAL; PROJECT MYTRI; YOUNG-PEOPLE; PROGRAM; INDIA; TRANSLATION AB Background: In response to India's growing tobacco epidemic, strategies are needed to decrease tobacco use among Indian youth, particularly among those who are economically disadvantaged. The objective of this study was to assess the effectiveness of a school-based life-skills tobacco control program for youth of low socio-economic status in Mumbai and the surrounding state of Maharashtra. We hypothesized that compared to youth in control schools, youth exposed to the program would have greater knowledge of effects of tobacco use; be more likely to take action to prevent others from using tobacco; demonstrate more positive life skills and attitudes; and be less likely to report tobacco use. Methods/Findings: Using a quasi-experimental design, we assessed program effectiveness by comparing 8th and 9th grade students in intervention schools to 8th grade students in comparable schools that did not receive the program. Across all schools, 1851 students completed a survey that assessed core program components in early 2010. The program consisted of activities focused on building awareness about the hazards of tobacco, developing life skills, and advocacy development. The primary outcome measure was self-reported tobacco use in the last 30 days. Findings indicate that 4.1% of 8th grade intervention students (OR = 0.51) and 3.6% of 9th grade intervention students (OR = 0.33) reported using tobacco at least once in the last 30 days, compared to 8.7% of students in the control schools. Intervention group students were also significantly more knowledgeable about tobacco and related legislation, reported more efforts to prevent tobacco use among others, and reported stronger life skills and self-efficacy than students in control schools. Limitations to the study include schools not being randomly assigned to condition and tobacco use being measured by self-report. Conclusions: This program represents an effective model of school-based tobacco use prevention that low-income schools in India and other low-and middle-income countries can replicate. C1 [Sorensen, Glorian; Nagler, Eve; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Sorensen, Glorian; Gupta, Prakash C.; Nagler, Eve; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gupta, Prakash C.] Healis, Sekhsaria Inst Publ Hlth, Navi Mumbai, India. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. EM Glorian_Sorensen@dfci.harvard.edu FU National Cancer Institute [K05 CA108663] FX Dr. Sorensen's effort was supported in part by her established investigator award from the National Cancer Institute (K05 CA108663). No additional external funding received for this study. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 4 Z9 4 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 16 PY 2012 VL 7 IS 4 AR e34982 DI 10.1371/journal.pone.0034982 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959VO UT WOS:000305345000039 PM 22523567 ER PT J AU Choi, SH Quinti, L Kazantsev, AG Silverman, RB AF Choi, Soo Hyuk Quinti, Luisa Kazantsev, Aleksey G. Silverman, Richard B. TI 3-(N-Arylsulfamoyl)benzamides, inhibitors of human sirtuin type 2 (SIRT2) SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Sirtuin 2; Neurodegenerative disease; 3-(N-Arylsulfamoyl)benzamides; Sirtuin selectivity; Hydrophobic pocket ID NAD(+)-DEPENDENT HISTONE DEACETYLASES; MECHANISM; INSIGHTS; DISEASE; ANALOGS; NAD(+) AB Inhibition of sirtuin 2 (SIRT2) is known to be protective against the toxicity of disease proteins in Parkinson's and Huntington's models of neurodegeneration. Previously, we developed SIRT2 inhibitors based on the 3-(N-arylsulfamoyl)benzamide scaffold, including3-(N-(4-bromophenyl)sulfamoyl)-N-(4-bromophenyl) benzamide(C2-8, 1a), which demonstrated neuroprotective effects in a Huntington's mouse model, but had low potency of SIRT2 inhibition. Here we report that N-methylation of 1a greatly increases its potency and results in excellent selectivity for SIRT2 over SIRT1 and SIRT3 isoforms. Structure-activity relationships observed for 1a analogs and docking simulation data suggest that the para-substituted amido moiety of these compounds could occupy two potential hydrophobic binding pockets in SIRT2. These results provide a direction for the design of potent drug-like SIRT2 inhibitors. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Choi, Soo Hyuk; Silverman, Richard B.] Northwestern Univ, Dept Chem, Chem Life Proc Inst, Ctr Mol Innovat & Drug Discovery, Evanston, IL 60208 USA. [Choi, Soo Hyuk; Silverman, Richard B.] Northwestern Univ, Dept Mol Biosci, Chem Life Proc Inst, Ctr Mol Innovat & Drug Discovery, Evanston, IL 60208 USA. [Quinti, Luisa; Kazantsev, Aleksey G.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Quinti, Luisa; Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Silverman, RB (reprint author), Northwestern Univ, Dept Chem, Chem Life Proc Inst, Ctr Mol Innovat & Drug Discovery, 2145 Sheridan Rd, Evanston, IL 60208 USA. EM r-silverman@northwestern.edu FU National Institutes of Health [5U01NS066912] FX The authors are grateful to the National Institutes of Health (5U01NS066912) for financial support of this research. NR 19 TC 8 Z9 8 U1 0 U2 12 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 APR 15 PY 2012 VL 22 IS 8 BP 2789 EP 2793 DI 10.1016/j.bmcl.2012.02.089 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 925NO UT WOS:000302768200031 PM 22446090 ER PT J AU Hutter, CM Chang-Claude, J Slattery, ML Pflugeisen, BM Lin, Y Duggan, D Nan, HM Lemire, M Rangrej, J Figueiredo, JC Jiao, S Harrison, TA Liu, Y Chen, LS Stelling, DL Warnick, GS Hoffmeister, M Kury, S Fuchs, CS Giovannucci, E Hazra, A Kraft, P Hunter, DJ Gallinger, S Zanke, BW Brenner, H Frank, B Ma, J Ulrich, CM White, E Newcomb, PA Kooperberg, C LaCroix, AZ Prentice, RL Jackson, RD Schoen, RE Chanock, SJ Berndt, SI Hayes, RB Caan, BJ Potter, JD Hsu, L Bezieau, S Chan, AT Hudson, TJ Peters, U AF Hutter, Carolyn M. Chang-Claude, Jenny Slattery, Martha L. Pflugeisen, Bethann M. Lin, Yi Duggan, David Nan, Hongmei Lemire, Mathieu Rangrej, Jagadish Figueiredo, Jane C. Jiao, Shuo Harrison, Tabitha A. Liu, Yan Chen, Lin S. Stelling, Deanna L. Warnick, Greg S. Hoffmeister, Michael Kuery, Sebastien Fuchs, Charles S. Giovannucci, Edward Hazra, Aditi Kraft, Peter Hunter, David J. Gallinger, Steven Zanke, Brent W. Brenner, Hermann Frank, Bernd Ma, Jing Ulrich, Cornelia M. White, Emily Newcomb, Polly A. Kooperberg, Charles LaCroix, Andrea Z. Prentice, Ross L. Jackson, Rebecca D. Schoen, Robert E. Chanock, Stephen J. Berndt, Sonja I. Hayes, Richard B. Caan, Bette J. Potter, John D. Hsu, Li Bezieau, Stephane Chan, Andrew T. Hudson, Thomas J. Peters, Ulrike TI Characterization of Gene-Environment Interactions for Colorectal Cancer Susceptibility Loci SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; COLON-CANCER; CHROMOSOME 8Q24; LIFE-STYLE; RISK LOCI; METAANALYSIS; HEALTH; VARIANTS; FRUIT; SCAN AB Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case-control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at 19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene-environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal P-interaction = 1.3 x 10(-4); adjusted P = 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS seems to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption. Cancer Res; 72(8); 2036-44. (C) 2012 AACR. C1 [Hutter, Carolyn M.; Pflugeisen, Bethann M.; Lin, Yi; Jiao, Shuo; Harrison, Tabitha A.; Stelling, Deanna L.; Warnick, Greg S.; Ulrich, Cornelia M.; White, Emily; Newcomb, Polly A.; Kooperberg, Charles; LaCroix, Andrea Z.; Prentice, Ross L.; Potter, John D.; Hsu, Li; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Hutter, Carolyn M.; Ulrich, Cornelia M.; White, Emily; Newcomb, Polly A.; Potter, John D.; Peters, Ulrike] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Kooperberg, Charles; Hsu, Li] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Hoffmeister, Michael; Brenner, Hermann; Frank, Bernd] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany. [Ulrich, Cornelia M.] German Canc Res Ctr, Div Prevent Oncol, D-6900 Heidelberg, Germany. [Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. [Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA. [Nan, Hongmei; Fuchs, Charles S.; Giovannucci, Edward; Hazra, Aditi; Ma, Jing; Chan, Andrew T.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Nan, Hongmei; Fuchs, Charles S.; Giovannucci, Edward; Hazra, Aditi; Ma, Jing; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Nan, Hongmei; Hazra, Aditi; Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Lemire, Mathieu; Rangrej, Jagadish; Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Gallinger, Steven] Toronto Gen Hosp, Univ Hlth Network, Dept Surg, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Figueiredo, Jane C.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Liu, Yan] Stephens & Associates, Carrollton, TX USA. [Chen, Lin S.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Kuery, Sebastien; Bezieau, Stephane] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. [Zanke, Brent W.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Schoen, Robert E.] Univ Pittsburgh, Dept Epidemiol, Med Ctr, Pittsburgh, PA 15261 USA. [Chanock, Stephen J.; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hayes, Richard B.] NYU, Sch Med, Dept Environm Med, Div Epidemiol, New York, NY USA. [Caan, Bette J.] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. RP Hutter, CM (reprint author), 1100 Fairview Ave N,M4-B402,POB 19024, Seattle, WA 98109 USA. EM chutter@fhcrc.org RI Gallinger, Steven/E-4575-2013; Hoffmeister, Michael/B-5745-2012; KURY, Sebastien/G-5971-2015; Bezieau, stephane/G-5621-2015; Brenner, Hermann/B-4627-2017; OI Hayes, Richard/0000-0002-0918-661X; Hoffmeister, Michael/0000-0002-8307-3197; KURY, Sebastien/0000-0001-5497-0465; Bezieau, stephane/0000-0003-0095-1319; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500 FU Ontario Research Fund; Canadian Institutes of Health Research; Canadian Cancer Society Research Institute; Ontario Institute for Cancer Research through Ontario Ministry of Research; regional Hospital Clinical Research Program (PHRC); Regional Council of Pays de la Loire; Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC); Association Anne de Bretagne Genetique; Ligue Regionale Contre le Cancer (LRCC); National Cancer Institute, NIH [CA-95-011]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; National Cancer Institute, NIH, U.S. Department of Health and Human Services [R01 CA48998]; National Cancer Institute; National Institutes of Health; U.S. Department of Health and Human Services [R01 CA059045, R25 CA094880, U01 CA137088]; Institutes of Health; NIH [P01 CA 055075, P50 CA 127003, R01 137178, P01 CA 087969]; Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention; NIH, Genes, Environment and Health Initiative [NIH GEI] [Z01 CP 010200, U01 HG 004438]; Gene Environment Association Studies, GENEVA Coordinating Center [U01 HG004446]; Johns Hopkins University Center for Inherited Disease Research; National Heart, Lung, and Blood Institute, NIH; U. S. Department of Health and Human Services [HHSN268201100001C-4C, HHSN268201100046C, HHSN271201100004C, NO1WH4421]; [U01 CA074783] FX ARTIC was supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. T.J. Hudson and B. W. Zanke are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research.; ASTERISK was supported by a regional Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Genetique, and the Ligue Regionale Contre le Cancer (LRCC).; CCFR was supported by the National Cancer Institute, NIH under RFA # CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. The Colon CFR Center, Ontario Registry for Studies of Familial CRC, contributed data to this manuscript and was supported by (U01 CA074783).; DACHS was supported by grants from the German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814).; DALS was supported by the National Cancer Institute, NIH, U.S. Department of Health and Human Services (R01 CA48998 to M.L. Slattery).; Funding for the genome-wide scan of DALS, PLCO, and WHI was provided by the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (R01 CA059045 to U. Peters). C.M. Hutter was supported by a training grant from the National Cancer Institute, Institutes of Health, U.S. Department of Health and Human Services (R25 CA094880). Additional funding for this work was provided by National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088 to U. Peters).; HPFS was supported by the NIH (P01 CA 055075 to C. S. Fuchs, R01 137178 to A. T. Chan, and P50 CA 127003 to C. S. Fuchs), NHS by the NIH (R01 137178 to A.T. Chan., P50 CA 127003 to C. S. Fuchs., and P01 CA 087969 to E. L. Giovannucci) and PHS by the NIH (CA41281).; PLCO was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, the Division of Cancer Prevention, National Cancer Institute, NIH, U.S. Department of Health and Human Services.; Control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) prostate cancer scan and were supported by the Intramural Research Program of the National Cancer Institute. The data sets used in this analysis were accessed with appropriate approval through the dbGaP online resource (54) through dbGaP accession number 000207v.1p1.c1 (20). Control samples were also genotyped as part of the GWAS of Lung Cancer and Smoking. This work was supported by NIH, Genes, Environment and Health Initiative [NIH GEI] (Z01 CP 010200). The human subjects participating in the GWAS are derived from the Prostate, Lung, Colon and Ovarian Screening Trial and the study is supported by intramural resources of the National Cancer Institute. Assistance with genotype cleaning, as well as with general study coordination, was provided by the Gene Environment Association Studies, GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was carried out at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01 HG 004438). The data sets used for the analyses described in this article were obtained from dbGaP through National Center for Biotechnology Information (55), through dbGaP accession number ph000093.v2.p2.c1. The WHI program was supported by the National Heart, Lung, and Blood Institute, NIH, U. S. Department of Health and Human Services through contracts HHSN268201100001C-4C, HHSN268201100046C and HHSN271201100004C, and NO1WH4421. NR 55 TC 64 Z9 67 U1 0 U2 22 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 APR 15 PY 2012 VL 72 IS 8 BP 2036 EP 2044 DI 10.1158/0008-5472.CAN-11-4067 PG 9 WC Oncology SC Oncology GA 927KH UT WOS:000302905700015 PM 22367214 ER PT J AU Ford, J Keedy, S Reilly, J Gershon, E Sweeney, JA AF Ford, Judith Keedy, Sarah Reilly, James Gershon, Elliott Sweeney, John A. 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TI Peritraumatic Psychological Distress and Mild Traumatic Brain Injury Symptoms (MTBI) are Associated in the Early Aftermath of Trauma SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Mild Traumatic Brain Injury; Peritraumatic Psychological Psychological Distress; Dissociative Symptoms; Motor Vehicle Collision; Postconcussive Symptoms C1 [Goetzinger, Amy M.; Orrey, Danielle; Lee, Young M.; Platts-Mills, Timothy F.; Bortsov, Andrey; McLean, Samuel A.] UNC, Chapel Hill, NC USA. [Swor, Robert] William Beaumont Hosp, Royal Oak, MI USA. [Peak, David] Mass Gen Hosp, Boston, MA USA. [Rathlev, Niels] Baystate Med Ctr, Springfield, MA USA. [Lee, David] N Shore Univ Hosp, Manhasset, NY USA. [Domeier, Robert] St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. [Hendry, Phyllis] Shands Jacksonville, Jacksonville, FL USA. [Liberzon, Israel] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 242 BP 75S EP 75S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000237 ER PT J AU Smith, J Bortsov, A Ulirsch, J Swor, R Peak, D Jones, J Rathlev, N Lee, D Domeier, R Henry, P Diatchenko, L Liberzon, I McLean, S AF Smith, Jennifer Bortsov, Andrey Ulirsch, Jacob Swor, Robert Peak, David Jones, Jeffrey Rathlev, Niels Lee, David Domeier, Robert Henry, Phyllis Diatchenko, Luda Liberzon, Israel McLean, Samuel TI FKBP5 Polymorphism Predicts Peritraumatic Dissociation after Motor Vehicle Collision SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE peri-traumatic dissociation; PTSD; FKBP506; MCEPS; trauma C1 [Smith, Jennifer; Bortsov, Andrey; Ulirsch, Jacob; Diatchenko, Luda; McLean, Samuel] Univ N Carolina, Chapel Hill, NC USA. [Swor, Robert] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Peak, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jones, Jeffrey] Spectrum Hlth Care, Emergency Med, Grand Rapids, MI USA. [Rathlev, Niels] Baystate Med Ctr, Springfield, MA USA. [Lee, David] N Shore Univ Hosp, Manhasset, NY USA. [Domeier, Robert] St Joseph Mercy Hlth Syst, Emergency Med, Ypsilanti, MI USA. [Henry, Phyllis] Univ Florida, Coll Med Jacksonville, Jacksonville, FL USA. [Liberzon, Israel] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 243 BP 75S EP 75S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000238 ER PT J AU Jahshan, C Wynn, JK Mathis, KI Gibson, C Tripp, C Weiner, K Green, MF AF Jahshan, Carol Wynn, Jonathan K. Mathis, Kristopher I. Gibson, Crystal Tripp, Cory Weiner, Katie Green, Michael F. TI Cross-Diagnostic Comparison of Mismatch Negativity and P3a in Bipolar Disorder and Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE bipolar disorder; schizophrenia; mismatch negativity; P3a; auditory processing C1 W Los Angeles VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 261 BP 81S EP 81S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000256 ER PT J AU Niznikiewicz, MA AF Niznikiewicz, Margaret A. TI Processing Information from Face and Voice in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE face processing; voice processing; sensory integration C1 [Niznikiewicz, Margaret A.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Niznikiewicz, Margaret A.] VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 275 BP 85S EP 85S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000270 ER PT J AU Hurford, IM March, ME Richard, J Gur, RE Gur, RC AF Hurford, Irene M. March, Mary E. Richard, Jan Gur, Raquel E. Gur, Ruben C. TI A Brief Cognitive Assessment Tool for Schizophrenia (B-CATS): Correlation of a 10-Minute Clinical Tool with a Computerized Neurocognitive Battery SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Schizophrenia; Cognition; Assessment; Neuropsychology C1 [Hurford, Irene M.; March, Mary E.; Richard, Jan; Gur, Raquel E.; Gur, Ruben C.] Univ Penn, Philadelphia, PA 19104 USA. [Hurford, Irene M.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 303 BP 94S EP 94S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000298 ER PT J AU Ghorashi, S Spencer, KM AF Ghorashi, Shahab Spencer, Kevin M. TI The Effects of Visual Stimulus Properties on Gamma Oscillations in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Schizophrenia; Gamma Oscillations; Visual Stimulus Properties; Luminance; Motion C1 [Ghorashi, Shahab; Spencer, Kevin M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 310 BP 96S EP 96S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000305 ER PT J AU Mears, R Spencer, K AF Mears, Ryan Spencer, Kevin TI Oscillatory Measures of Auditory Neuroplasticity in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Schizophrenia; Plasticity; Gamma; oscillations; 40 Hz C1 [Mears, Ryan; Spencer, Kevin] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 311 BP 97S EP 97S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000306 ER PT J AU Smoller, JW AF Smoller, Jordan W. TI Genetic Studies of Anxiety-Related Temperament and Brain Function SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE behavioral inhibition; RTN4; amygdala; temperament; anxiety C1 [Smoller, Jordan W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 2012 VL 71 IS 8 SU S MA 372 BP 116S EP 116S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000367 ER PT J AU Guha, S Rees, E Darvasi, A Ivanov, D Ikeda, M Bergen, SE Magnusson, PK Cormican, P Cihon, S Rosenfeld, JA Malhotra, AK Rujescu, D Ruderfer, D Purcell, S Sklar, P Iwata, N Hultman, CM Sullivan, P Sebat, J McCarthy, S Levinson, D Owen, MJ O'Donovan, MC Lencz, T Kirov, G AF Guha, Saurav Rees, Elliott Darvasi, Ariel Ivanov, Dobril Ikeda, Masashi Bergen, Sarah E. Magnusson, Patrik K. Cormican, Paul Cihon, Sven Rosenfeld, Jeffrey A. Malhotra, Anil K. Rujescu, Dan Ruderfer, Douglas Purcell, Shaun Sklar, Pamela Iwata, Nakao Hultman, Christina M. Sullivan, Patrick Sebat, Jonathan McCarthy, Shane Levinson, Douglas Owen, Michael J. O'Donovan, Michael C. Lencz, Todd Kirov, George TI A Rare Deletion At Distal 16p11.2 Is Implicated In Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Schizophrenia; CNV; 16p11.2 C1 [Guha, Saurav; Rosenfeld, Jeffrey A.; Malhotra, Anil K.; Lencz, Todd] NSLIJ, Glen Oaks, NY USA. [Rees, Elliott; Ivanov, Dobril] Cardiff Univ, Dept Psychol Med & Neurol, Cardiff, Wales. [Darvasi, Ariel] Hebrew Univ Jerusalem, Dept Genet, IL-91904 Jerusalem, Israel. [Ikeda, Masashi; Iwata, Nakao] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan. [Bergen, Sarah E.; Purcell, Shaun; Sklar, Pamela] Harvard Univ, Sch Med, Psychiat & Neurodev Genet Unit, Boston, MA USA. [Magnusson, Patrik K.; Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Cormican, Paul] Trinity Coll Dublin, Inst Mol Med, Dept Psychiat, Dublin, Ireland. [Cihon, Sven] Univ Bonn, Dept Psychiat, Bonn, Germany. [Rujescu, Dan] Univ Munich, Dept Psychiat, D-8000 Munich, Germany. [Ruderfer, Douglas] Mass Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA USA. [Sullivan, Patrick] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Sebat, Jonathan] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Sebat, Jonathan] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [McCarthy, Shane] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Levinson, Douglas] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Owen, Michael J.; O'Donovan, Michael C.; Kirov, George] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Cardiff, Wales. RI Bergen, Sarah/I-8313-2012; Ruderfer, Douglas/M-5795-2016; Magnusson, Patrik/C-4458-2017 OI Ruderfer, Douglas/0000-0002-2365-386X; NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 15 PY 2012 VL 71 IS 8 SU S MA 387 BP 120S EP 121S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000382 ER PT J AU Ballina, LE Diatchenko, L Ulirsch, J Swor, R Peak, D Jones, J Rathlev, N Lee, D Domeier, R Hendry, P Liberzon, I McLean, S AF Ballina, Lauren E. Diatchenko, Luda Ulirsch, Jacob Swor, Robert Peak, David Jones, Jeffrey Rathlev, Niels Lee, David Domeier, Robert Hendry, Phyllis Liberzon, Israel McLean, Samuel TI Sexually Dimorphic Influence of COMT on Distress in the Immediate Aftermath of Trauma SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Peritraumatic Distress; Catechol O-Methyltransferase; Trauma C1 [Diatchenko, Luda] Univ N Carolina, Sch Dent, Ctr Neurosensory Disorders, Chapel Hill, NC USA. [Swor, Robert] Wayne State Univ, Royal Oak, MI USA. [Peak, David] Massachuesetts Gen Hosp, Boston, MA USA. [Jones, Jeffrey] Spectrum Hlth, Emergency Med, Grand Rapids, MI USA. [Rathlev, Niels] Baystate Med Ctr, Springfield, MA USA. [Lee, David] N Shore Univ Hosp, Manhasset, NY USA. [Domeier, Robert] St Joseph Mercy Hlth Syst, Emergency Med, Ann Arbor, MI USA. [Hendry, Phyllis] Univ Florida, Jacksonville, FL USA. [Liberzon, Israel] Univ Michigan, Sch Med, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 472 BP 148S EP 148S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000467 ER PT J AU Ulirsch, J Bortsov, A Smith, J Swor, R Peak, D Jones, J Rathlev, N Lee, D Domeier, R Henry, P Liberzon, I McLean, S AF Ulirsch, Jacob Bortsov, Andrey Smith, Jennifer Swor, Robert Peak, David Jones, Jeffrey Rathlev, Niels Lee, David Domeier, Robert Henry, Phyllis Liberzon, Israel McLean, Samuel TI ADRA2A Variants Predict Peritraumatic Dissociation After Motor Vehicle Collision SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE ADRA2A; MVC; Peritraumatic C1 [Ulirsch, Jacob; Bortsov, Andrey; Smith, Jennifer; McLean, Samuel] Univ N Carolina, Chapel Hill, NC USA. [Swor, Robert] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Peak, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jones, Jeffrey] Spectrum Hlth Care, Emergency Med, Grand Rapids, MI USA. [Rathlev, Niels] Baystate Med Ctr, Springfield, MA USA. [Lee, David] N Shore Univ Hosp, Manhasset, NY USA. [Domeier, Robert] St Joseph Mercy Hlth Syst, Emergency Med, Ypsilanti, MI USA. [Henry, Phyllis] Univ Florida, Coll Med Jacksonville, Jacksonville, FL USA. [Liberzon, Israel] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 473 BP 148S EP 148S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000468 ER PT J AU Bortsov, A Soward, A Diatchenko, L Ulirsch, J Swor, R Peak, D Jones, J Rathlev, N Lee, D Domeier, R Hendry, P Liberzon, I McLean, S AF Bortsov, Andrey Soward, April Diatchenko, Luda Ulirsch, Jacob Swor, Robert Peak, David Jones, Jeffrey Rathlev, Niels Lee, David Domeier, Robert Hendry, Phyllis Liberzon, Israel McLean, Samuel TI Tryptophan Hydroxylase 2 Synonymous Polymorphism rs7305115 is Associated with Acute Psychological Response after Motor Vehicle Collision SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE peritraumatic distress; Tryptophan Hydroxylase 2; polymorphism C1 [Diatchenko, Luda] Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC USA. [Swor, Robert] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Peak, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jones, Jeffrey] Spectrum Hlth Hosp, Grand Rapids, MI USA. [Rathlev, Niels] Baystate Med Ctr, Springfield, MA USA. [Lee, David] N Shore Univ Hosp, Manhasset, NY USA. [Domeier, Robert] St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. [Hendry, Phyllis] Univ Florida, Jacksonville, FL USA. [Liberzon, Israel] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 474 BP 149S EP 149S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000469 ER PT J AU Perez-Rodriguez, MM Roussos, P Bevilacqua, L Yuan, QP Zhou, ZF Hodgkinson, C Ripoll, L Goodman, M Koenigsberg, HW Goldman, D Siever, LJ New, AS AF Perez-Rodriguez, M. Mercedes Roussos, Panos Bevilacqua, Laura Yuan, Qiaoping Zhou, Zhifeng Hodgkinson, Colin Ripoll, Luis Goodman, Marianne Koenigsberg, Harold W. Goldman, David Siever, Larry J. New, Antonia S. TI Exploratory Association Study of 130 Candidate Genes in Patients with Borderline Personality Disorder and Healthy Controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Borderline Personality Disorder; Genetics; Dopamine beta hydroxylase; Association study C1 [Perez-Rodriguez, M. Mercedes; Roussos, Panos; Ripoll, Luis; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.; New, Antonia S.] Mt Sinai Sch Med, New York, NY USA. [Perez-Rodriguez, M. Mercedes; Roussos, Panos; Ripoll, Luis; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.; New, Antonia S.] James J Peters Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr, Bronx, NY USA. [Bevilacqua, Laura; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. RI Perez Rodriguez, Maria/B-9410-2013; Roussos, Panos/J-7090-2013 OI Perez Rodriguez, Maria/0000-0001-5137-1993; Roussos, Panos/0000-0002-4640-6239 NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 15 PY 2012 VL 71 IS 8 SU S MA 492 BP 155S EP 155S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000487 ER PT J AU Yao, JK Reddy, RD Doughedy, GG Magan, S Gurklis, J Sonel, A Sonel, E Kisslinger, BL Chengappa, RKN Keshavan, MS AF Yao, Jeffrey K. Reddy, Ravinder D. Doughedy, George G. Magan, Sharon Gurklis, John Sonel, Ali Sonel, Elif Kisslinger, Benjamin L. Chengappa, Roy K. N. Keshavan, Matcheri S. TI Association of hsCRP with High-Risk of Cardiovascular Disease in Patients with Early Course Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE high-sensitivity C-reactive protein; Early course schizophrenia; Cardiovascular disease; HDL cholesterol; Lipoprotein (a) C1 [Reddy, Ravinder D.; Chengappa, Roy K. N.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.; Doughedy, George G.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Magan, Sharon; Gurklis, John; Kisslinger, Benjamin L.] VA Pittsburgh Healthcare Syst, Med Serv, Pittsburgh, PA USA. [Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Keshavan, Matcheri S.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 534 BP 168S EP 169S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000529 ER PT J AU Rabinak, CA Angstadt, M Sripada, CS Milad, MR Phan, KL AF Rabinak, Christine A. Angstadt, Mike Sripada, Chandra S. Milad, Mohammed R. Phan, K. Luan TI Cannabinoid Modulation of Fear Extinction Learning and Underlying Brain Circuitry in Healthy Humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Pavlovian fear extinction; cannabinoids; ventromedial prefrontal cortex; hippocampus; amygdala C1 [Rabinak, Christine A.; Angstadt, Mike; Sripada, Chandra S.; Phan, K. Luan] Univ Michigan, Ann Arbor, MI 48109 USA. [Milad, Mohammed R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Boston, MA USA. [Phan, K. Luan] Univ Illinois, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 15 PY 2012 VL 71 IS 8 SU S MA 562 BP 177S EP 177S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000557 ER PT J AU Barbour, T Diwadkar, V AF Barbour, Tracy Diwadkar, Vaibhav TI A Framework for Understanding Monetary and Social Reward Processing in Adolescence: Relevance for the Emergence of Psychiatric Illness SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Reward; Development; Vulnerable; Adolescence; fMRI C1 [Barbour, Tracy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Diwadkar, Vaibhav] Wayne State Univ, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 571 BP 180S EP 180S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000566 ER PT J AU Brown, AB Lomedico, A Biederman, J AF Brown, Ariel B. Lomedico, Alexandra Biederman, Joseph TI Effect of Psychostimulants on Brain Structure and Function in Adhd: A Comprehensive Literature Review of MRI-Based Neuroimaging Studies SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE ADHD; psychostimulants; neuroimaging; MRI; review C1 [Brown, Ariel B.; Lomedico, Alexandra; Biederman, Joseph] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Brown, Ariel B.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 587 BP 186S EP 186S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000582 ER PT J AU Joshi, G Gabrieli, SW Biederman, J Goldin, RL Reynolds, G Gabrieli, J AF Joshi, Gagan Gabrieli, Susan Whitfield Biederman, Joseph Goldin, Rachel L. Reynolds, Gretchen Gabrieli, John TI Resting State Default Mode Functional Connectivity in Adolescent and Young Adult Males with High-Functioning Autism Spectrum Disorders: An fMRI Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Autism; Pervasive Developmental Disorder; Imaging C1 [Joshi, Gagan; Biederman, Joseph; Goldin, Rachel L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gabrieli, Susan Whitfield; Reynolds, Gretchen; Gabrieli, John] MIT, Cognit & Affect Neurosci Lab, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 4 U2 8 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 APR 15 PY 2012 VL 71 IS 8 SU S MA 588 BP 186S EP 186S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000583 ER PT J AU Vizueta, N Townsend, JD Torrisi, S Aquino, AR Fischer, J Bookheimer, SY Altshuler, LL AF Vizueta, Nathalie Townsend, Jennifer D. Torrisi, Salvatore Aquino, Ana R. Fischer, Jeffrey Bookheimer, Susan Y. Altshuler, Lori L. TI Elucidating State Versus Trait-Related Functional MRI Deficits in Bipolar II Disorder: A Longitudinal Investigation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Bipolar II Disorder; functional MRI; emotional faces; amygdala; treatment response C1 [Vizueta, Nathalie; Townsend, Jennifer D.; Torrisi, Salvatore; Aquino, Ana R.; Fischer, Jeffrey; Bookheimer, Susan Y.; Altshuler, Lori L.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Altshuler, Lori L.] W Los Angles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 APR 15 PY 2012 VL 71 IS 8 SU S MA 646 BP 206S EP 206S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466000641 ER PT J AU Bellin, E Wong, E Simantov, J Bang, C Hazlett, E Elder, G Tang, CY Carpenter, D Mitsis, EM AF Bellin, Elisheva Wong, Edmund Simantov, Jessie Bang, Charlene Hazlett, Erin Elder, Gregory Tang, Cheuk Y. Carpenter, David Mitsis, Effie M. TI Resting State Functional Connectivity in Blast-Related Mild Traumatic Brain Injury in OIF/OEF Combat Veterans With and Without PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE fMRI; Default Mode Network; blast related mild TBI; combat veterans C1 [Bellin, Elisheva; Simantov, Jessie; Bang, Charlene; Elder, Gregory; Mitsis, Effie M.] James J Peters VAMC, Bronx, NY USA. [Wong, Edmund; Hazlett, Erin; Elder, Gregory; Tang, Cheuk Y.; Carpenter, David; Mitsis, Effie M.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 11 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 APR 15 PY 2012 VL 71 IS 8 SU S MA 786 BP 247S EP 248S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001099 ER PT J AU Rosell, DR Mennes, M Chu, KW New, AS Siever, LJ Milham, MP Hazlett, EA AF Rosell, Daniel R. Mennes, Maarten Chu, King-Wai New, Antonia S. Siever, Larry J. Milham, Michael P. Hazlett, Erin A. TI Distinct Patterns of Altered Fronto-Parietal and Cingulo-Opercular Network Functional Connectivity in Borderline and Schizotypal Personality Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE functional connectivity; borderline; schizotypal; task positive; default mode C1 [Rosell, Daniel R.; New, Antonia S.; Siever, Larry J.; Hazlett, Erin A.] Mt Sinai Sch Med, New York, NY USA. [Chu, King-Wai; New, Antonia S.; Siever, Larry J.; Hazlett, Erin A.] James J Peters VA Med Ctr, VISN3 MIRECC, Bronx, NY USA. [Mennes, Maarten] NYU Langone Sch Med, Phyllis Green & Randolph Cowen Inst Pediat Neuros, New York, NY USA. [Milham, Michael P.] Child Mind Inst, Ctr Developing Brain, New York, NY USA. RI Mennes, Maarten/C-9924-2011 OI Mennes, Maarten/0000-0002-7279-3439 NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 15 PY 2012 VL 71 IS 8 SU S MA 792 BP 249S EP 249S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001105 ER PT J AU Brent, BK Coombs, G Keshavan, MS Seidman, LJ Moran, JM Holt, DJ AF Brent, Benjamin K. Coombs, Garth Keshavan, Matcheri S. Seidman, Larry J. Moran, Joseph M. Holt, Daphne J. TI Delusional Thinking in Non-Clinical Subjects is Associated with Reduced Activity and Functional Connectivity of the Lateral Temporal Cortex SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Delusions; Social Cognition; Lateral Temporal Cortex; Default Mode Network; Functional Connectivity C1 [Brent, Benjamin K.; Keshavan, Matcheri S.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Coombs, Garth] MGH Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Moran, Joseph M.] MIT, Cambridge, MA 02139 USA. [Holt, Daphne J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 794 BP 250S EP 250S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001107 ER PT J AU Vu, MAT Kikinis, Z Peled, S Kulkarni, P Ferris, C Bouix, S Makinodan, M Kubicki, M Corfas, G Shenton, M AF Vu, Mai-Anh T. Kikinis, Zora Peled, Sharon Kulkarni, Praveen Ferris, Craig Bouix, Sylvain Makinodan, Manabu Kubicki, Marek Corfas, Gabriel Shenton, Martha TI Changes in Myelination of the Anterior Commissure in Mice with Loss of ErbB Receptor Signalling in Oligodendrocytes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE diffusion tensor imaging; tractography; myelination; transgenic animal; schizophrenia C1 [Vu, Mai-Anh T.; Kikinis, Zora; Peled, Sharon; Bouix, Sylvain; Kubicki, Marek; Shenton, Martha] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Kulkarni, Praveen; Ferris, Craig] Northeastern Univ, Boston, MA 02115 USA. [Makinodan, Manabu; Corfas, Gabriel] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Kubicki, Marek; Shenton, Martha] VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 795 BP 250S EP 250S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001108 ER PT J AU Levitt, J Vu, MAT Lucia, DM Bobrow, LH Smith, KM McCarley, RW Shenton, ME AF Levitt, James Vu, Mai-Anh T. Lucia, Diandra M. Bobrow, Laurel H. Smith, Katherine M. McCarley, Robert W. Shenton, Martha E. TI Anterior Cingulate Gyrus Morphometry and Paracingulate Sulcus Pattern in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE MRI; Schizophrenia; cingulate; paracingulate sulcus; cognition C1 [Levitt, James; McCarley, Robert W.; Shenton, Martha E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. [Levitt, James; Vu, Mai-Anh T.; Lucia, Diandra M.; Bobrow, Laurel H.; Smith, Katherine M.; Shenton, Martha E.] Harvard Univ, Sch Med, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 809 BP 255S EP 255S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001122 ER PT J AU Levitt, J Pelavin, PE Ballinger, T McCarley, RW Shenton, ME AF Levitt, James Pelavin, Paula E. Ballinger, Tom McCarley, Robert W. Shenton, Martha E. TI A Study of Striatal Gray Matter Volumes and WM Diffusivity Measures of the Anterior Limb of the Internal Capsule in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE MRI; DTI; Schizophrenia; Striatum; Anterior Limb of the Internal Capsule C1 [Levitt, James; McCarley, Robert W.; Shenton, Martha E.] Harvard Univ, VA Boston Healthcare Syst, Sch Med, Brockton, MA 02401 USA. [Levitt, James; Pelavin, Paula E.; Ballinger, Tom; Shenton, Martha E.] Harvard Univ, Sch Med, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 810 BP 256S EP 256S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001123 ER PT J AU Thermenos, H Whitfield-Gabrieli, S Juelich, R Makris, N Faraone, SV Tsuang, MT Gabrieli, JDE Seidman, L AF Thermenos, Heidi Whitfield-Gabrieli, Susan Juelich, Richard Makris, Nikos Faraone, Stephen V. Tsuang, Ming T. Gabrieli, John D. E. Seidman, Larry TI Specific Default Network Connectivity Patterns in Adolescent and Young Adult Relatives of Individuals with Bipolar Psychotic Disorder or Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Schizophrenia; Bipolar Disorder; Genetics; Functional MRI; Default C1 [Thermenos, Heidi; Juelich, Richard; Makris, Nikos; Seidman, Larry] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Thermenos, Heidi; Seidman, Larry] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA 02115 USA. [Whitfield-Gabrieli, Susan; Gabrieli, John D. E.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, Susan; Gabrieli, John D. E.] MIT, Poitras Ctr Affect Disorders Res, Cambridge, MA 02139 USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY USA. [Tsuang, Ming T.] Univ Calif San Diego, Ctr Behav Genom, Dept Psychiat, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 813 BP 256S EP 257S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001126 ER PT J AU Coombs, G Goff, DC Milad, MR Holt, DJ AF Coombs, Garth Goff, Donald C. Milad, Mohammed R. Holt, Daphne J. TI Frontotemporal Connectivity Predicts Amygdala and Hippocampal Responses During Fear Conditioning in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Schizophrenia; Amygdala; Medial Prefrontal Cortex; Connectivity; Fear C1 [Coombs, Garth; Goff, Donald C.; Milad, Mohammed R.; Holt, Daphne J.] Massachusetts Gen Hosp, Charlestown, MA USA. [Coombs, Garth; Milad, Mohammed R.; Holt, Daphne J.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Goff, Donald C.; Milad, Mohammed R.; Holt, Daphne J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 821 BP 259S EP 260S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001134 ER PT J AU Hazlett, EA Carpenter, D Goldstein, KE Haznedar, MM New, A Goodman, M Byne, W Siever, LJ Koenigsberg, HW Chu, KW AF Hazlett, Erin A. Carpenter, David Goldstein, Kim E. Haznedar, M. Mehmet New, Antonia Goodman, Marianne Byne, William Siever, Larry J. Koenigsberg, Harold W. Chu, King-Wai TI White Matter Integrity in Schizophrenia and Schizotypal Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE schizophrenia; schizotypal personality disorder; diffusion tensor imaging; white matter; cingulum C1 [Hazlett, Erin A.; Carpenter, David; Goldstein, Kim E.; Haznedar, M. Mehmet; New, Antonia; Goodman, Marianne; Byne, William; Siever, Larry J.; Koenigsberg, Harold W.] Mt Sinai Sch Med, New York, NY USA. [Hazlett, Erin A.; New, Antonia; Goodman, Marianne; Byne, William; Siever, Larry J.; Chu, King-Wai] James J Peters VAMC, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 824 BP 261S EP 261S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001137 ER PT J AU Fryer, SL Woods, SW Shanbhag, H Kiehl, KA Calhoun, VD Pearlson, GD Roach, BJ Ford, JM McGlashan, TH Mathalon, DH AF Fryer, Susanna L. Woods, Scott W. Shanbhag, Harshad Kiehl, Kent A. Calhoun, Vince D. Pearlson, Godfrey D. Roach, Brain J. Ford, Judith M. McGlashan, Thomas H. Mathalon, Daniel H. TI Functional Connectivity Alterations During Auditory Target Detection in Youth at Clinical High-Risk for Psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE schizophrenia prodrome; psychosis risk; functional connectivity; auditory oddball; dorsolateral prefrontal cortex C1 [Fryer, Susanna L.; Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fryer, Susanna L.; Shanbhag, Harshad; Roach, Brain J.; Ford, Judith M.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Woods, Scott W.; Calhoun, Vince D.; Pearlson, Godfrey D.; McGlashan, Thomas H.; Mathalon, Daniel H.] Yale Univ, New Haven, CT USA. [Kiehl, Kent A.; Calhoun, Vince D.] Univ New Mexico, Albuquerque, NM 87131 USA. [Kiehl, Kent A.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [Pearlson, Godfrey D.] Olin Neuropsychiat Res Ctr, Inst Living, Hartford, CT USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 837 BP 265S EP 265S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001150 ER PT J AU Hirano, Y Niznikiewicz, MA Naoya, O Tasoff, T del Re, E McCarley, RW Spencer, KM AF Hirano, Yoji Niznikiewicz, Margaret A. Naoya, Oribe Tasoff, Tammy del Re, Elisabetta McCarley, Robert W. Spencer, Kevin M. TI Abnormal Gamma-Band Auditory Steady-State Responses in Prodromal Syndromes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Prodromal syndromes; Neural oscillation; Auditory steady state response; Electroencephalogram C1 [Hirano, Yoji; Niznikiewicz, Margaret A.; Naoya, Oribe; Tasoff, Tammy; del Re, Elisabetta; McCarley, Robert W.; Spencer, Kevin M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 847 BP 268S EP 269S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001160 ER PT J AU Behr, GA Frey, BN Cohen, LS Moreira, JCF Otto, MW Harlow, BL Soares, CN AF Behr, Guilherme A. Frey, Benicio N. Cohen, Lee S. Moreira, Jose C. F. Otto, Michael W. Harlow, Bernard L. Soares, Claudio N. TI Peripheral Biomarkers in New Onset of Major Depressive Disorder in Midlife Women: The Harvard Study of Moods and Cycles SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE menopause transition; peripheral markers; major depression disorder; first-onset MDD C1 [Behr, Guilherme A.; Frey, Benicio N.; Soares, Claudio N.] McMaster Univ, Womens Hlth Concerns Clin, Hamilton, ON, Canada. [Behr, Guilherme A.; Frey, Benicio N.; Soares, Claudio N.] McMaster Univ, Mood Disorders Program, Hamilton, ON, Canada. [Behr, Guilherme A.; Moreira, Jose C. F.] Univ Fed Rio Grande do Sul, Dept Biochem, Porto Alegre, RS, Brazil. [Behr, Guilherme A.; Frey, Benicio N.; Soares, Claudio N.] McMaster Univ, McMaster Integrat Neurosci Discovery & Study MiND, Hamilton, ON, Canada. [Behr, Guilherme A.] Minist Educ Brazil, Capes Fdn, Brasilia, DF, Brazil. [Cohen, Lee S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Otto, Michael W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Harlow, Bernard L.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RI Behr, Guilherme/F-7062-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 877 BP 278S EP 278S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001190 ER PT J AU Gurrera, R AF Gurrera, Ronald TI Symptom Level and Cognitive Dysfunction Contribute to Personality Deviance in First Episode Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE personality; cognition; symptoms; schizophrenia C1 [Gurrera, Ronald] Harvard Univ, Sch Med, Brockton, MA USA. [Gurrera, Ronald] VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 894 BP 283S EP 283S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001207 ER PT J AU Offringa, R Staples, L Panic, P Hakim, B Van Elzakker, M Carter, N Dubois, S Cruz, F Milad, M Shin, LM AF Offringa, Reid Staples, Lindsay Panic, Philip Hakim, Belal Van Elzakker, Michael Carter, Nicole Dubois, Stacey Cruz, Fernando Milad, Mohammed Shin, Lisa M. TI Attenuated Differential Fear Conditioning is a Familial Risk Factor for PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE PTSD; fear conditioning; twins C1 [Offringa, Reid; Hakim, Belal; Van Elzakker, Michael; Carter, Nicole; Cruz, Fernando; Shin, Lisa M.] Tufts Univ, Medford, MA 02155 USA. [Offringa, Reid; Staples, Lindsay; Panic, Philip; Van Elzakker, Michael; Dubois, Stacey; Milad, Mohammed; Shin, Lisa M.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 2 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 APR 15 PY 2012 VL 71 IS 8 SU S MA 965 BP 304S EP 304S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001277 ER PT J AU McGrath, LM Kunwar, PS Crane, J Kagan, J Snidman, NC Smoller, JW Schwartz, C AF McGrath, Lauren M. Kunwar, Pratap S. Crane, Jacquelyn Kagan, Jerome Snidman, Nancy C. Smoller, Jordan W. Schwartz, Carl TI Multivariate Genetic Association Analysis of a Complex Developmental Phenotype Defined by Infant Temperament and Adolescent Neuroimaging SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE anxiety; temperament; childhood; individual differences; intermediate phenotype C1 [McGrath, Lauren M.; Crane, Jacquelyn; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [McGrath, Lauren M.; Snidman, Nancy C.; Smoller, Jordan W.; Schwartz, Carl] Harvard Univ, Sch Med, Boston, MA USA. [Kunwar, Pratap S.; Schwartz, Carl] Massachusetts Gen Hosp, Dev Neuroimaging & Psychopathol Lab, Dept Psychiat, Boston, MA USA. [Kunwar, Pratap S.; Schwartz, Carl] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kagan, Jerome] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Snidman, Nancy C.] Childrens Hosp, Child Dev Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 15 PY 2012 VL 71 IS 8 SU S MA 980 BP 308S EP 309S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001291 ER PT J AU Garrett, CT Alexander, PP Fisher, MA So, RP Powell, VBS Vinogradov, S AF Garrett, Coleman T. Alexander, Phillip P. Fisher, Melissa A. So, Rachel P. Powell, V. Brooke S. Vinogradov, Sophia TI Neuroplasticity-Based Cognitive Training Generalizes to Improved Semantic Clustering in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 67th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2012 CL Philadelphia, PA SP Soc Biol Psychiat DE Cognitive Training; Schizophrenia; Semantic Clustering C1 [Garrett, Coleman T.; Alexander, Phillip P.; So, Rachel P.; Powell, V. Brooke S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Fisher, Melissa A.; Vinogradov, Sophia] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 SU S MA 1003 BP 316S EP 316S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GL UT WOS:000302466001314 ER PT J AU Malkoski, SP Haeger, SM Cleaver, TG Rodriguez, KJ Li, H Lu, SL Feser, WJ Baron, AE Merrick, D Lighthall, JG Ijichi, H Franklin, W Wang, XJ AF Malkoski, Stephen P. Haeger, Sarah M. Cleaver, Timothy G. Rodriguez, Karen J. Li, Howard Lu, Shi-Long Feser, William J. Baron, Anna E. Merrick, Daniel Lighthall, Jessyka G. Ijichi, Hideaki Franklin, Wilbur Wang, Xiao-Jing TI Loss of Transforming Growth Factor Beta Type II Receptor Increases Aggressive Tumor Behavior and Reduces Survival in Lung Adenocarcinoma and Squamous Cell Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID TGF-BETA; DEFECTIVE EXPRESSION; HISTOLOGICAL TYPES; MOUSE MODELS; BASAL-CELLS; STEM-CELLS; CANCER; METASTASIS; HEAD; MICE AB Purpose: Lung adenocarcinoma and lung squamous cell carcinoma (SCC) are the most common non-small cell lung cancer (NSCLC) subtypes. This study was designed to determine whether reduced expression of TGF beta type II receptor (TGF beta RII) promotes lung adenocarcinoma and SCC carcinogenesis. Experimental Design: We examined TGF beta RII expression at the protein and mRNA levels in human NSCLC samples and assessed the relationship between TGF beta RII expression and clinicopathologic parameters. To determine whether sporadic TGF beta RII deletion in airway epithelial cells induces NSCLC formation, we targeted TGF beta RII deletion alone and in combination with oncogenic Kras(G12D) to murine airways using a keratin 5 (K5) promoter and inducible Cre recombinase. Results: Reduced TGF beta RII expression in human NSCLC is associated with male gender, smoking, SCC histology, reduced differentiation, increased tumor stage, increased nodal metastasis, and reduced survival. Homozygous or heterozygous TGF beta RII deletion in mouse airway epithelia increases the size and number of Kras(G12D)-initiated adenocarcinoma and SCC. TGF beta RII deletion increases proliferation, local inflammation, and TGF beta ligand elaboration; TGF beta RII knockdown in airway epithelial cells increases migration and invasion. Conclusions: Reduced TGF beta RII expression in human NSCLC is associated with more aggressive tumor behavior and inflammation that is, at least partially, mediated by increased TGF beta 1 expression. TGF beta RII deletion in mouse airway epithelial cells promotes adenocarcinoma and SCC formation, indicating that TGF beta RII loss plays a causal role in lung carcinogenesis. That TGF beta RII shows haploid insufficiency suggests that a 50% TGF beta RII protein reduction would negatively impact lung cancer prognosis. Clin Cancer Res; 18(8); 2173-83. (C) 2012 AACR. C1 [Malkoski, Stephen P.; Haeger, Sarah M.; Cleaver, Timothy G.; Rodriguez, Karen J.; Li, Howard] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Colorado Sch Publ Hlth, Aurora, CO 80045 USA. [Malkoski, Stephen P.; Franklin, Wilbur; Wang, Xiao-Jing] Univ Colorado Denver, Dept Pathol, Colorado Sch Publ Hlth, Aurora, CO 80045 USA. [Lu, Shi-Long; Wang, Xiao-Jing] Univ Colorado Denver, Dept Otolaryngol, Colorado Sch Publ Hlth, Aurora, CO 80045 USA. [Feser, William J.; Baron, Anna E.] Univ Colorado Denver, Dept Biostat & Informat, Colorado Sch Publ Hlth, Aurora, CO 80045 USA. [Merrick, Daniel] Denver VA Med Ctr, Dept Pathol, Denver, CO USA. [Ijichi, Hideaki] Univ Tokyo, Dept Gastroenterol, Tokyo, Japan. [Lighthall, Jessyka G.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Malkoski, SP (reprint author), Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Colorado Sch Publ Hlth, 12700 E 19th Ave,RC2,Room 9112,Mail Stop C272, Aurora, CO 80045 USA. EM Stephen.Malkoski@ucdenver.edu; XJ.Wang@ucdenver.edu FU NIH/NCI [F32 CA119467, K08 CA131483]; NIH/NIDCR [R01 DE015953]; Oregon Medical Research Foundation; National Lung Cancer Partnership; [T32 CA106195]; [P30 CA 069533]; [P30 CA046934]; [P50 CA058187] FX This work was supported by the NIH/NCI (F32 CA119467 and K08 CA131483 to S. P. Malkoski) and NIH/NIDCR (R01 DE015953 to X.-J. Wang). S. P. Malkoski was also supported by T32 CA106195, the Oregon Medical Research Foundation, and the National Lung Cancer Partnership. The OHSU BioLibrary is supported by P30 CA 069533 and the Colorado Lung SPORE Tissue Bank is supported by P30 CA046934 and P50 CA058187. NR 41 TC 24 Z9 25 U1 0 U2 5 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 APR 15 PY 2012 VL 18 IS 8 BP 2173 EP 2183 DI 10.1158/1078-0432.CCR-11-2557 PG 11 WC Oncology SC Oncology GA 927KW UT WOS:000302907300009 PM 22399565 ER PT J AU Chen, XY Zeng, QY Wu, MX AF Chen, Xinyuan Zeng, Qiyan Wu, Mei X. TI Improved Efficacy of Dendritic Cell-Based Immunotherapy by Cutaneous Laser Illumination SO CLINICAL CANCER RESEARCH LA English DT Article ID ANTITUMOR IMMUNITY; DEFICIENT MICE; CULTURE MODEL; LYMPH-NODES; MIGRATION; CANCER; VACCINES; SKIN; METALLOPROTEINASE-9; TRAFFICKING AB Purpose: The present study investigates a convenient laser-based approach to enhance dendritic cell (DC) migration and improve DC-based immunotherapy in murine models. Experimental Design: Influence of laser illumination on dermal tissue microenvironment and migration of DCs following intradermal injection were determined by whole-mount immunohistochemistry, transmission electron microscope, and flow cytometry. We also investigated in vivo expansion of CTLs by flow cytometry, CTL activity by in vitro CTL assay, and antitumor efficacy of DC immunization following cutaneous laser illumination in both preventive and therapeutic tumor models. Results: Laser illumination was found to significantly enlarge perforations in the perilymphatic basement membrane, disarray collagen fibers, and disrupt cell-matrix interactions in the dermis. The altered dermal tissue microenvironment permitted more efficient migration of intradermally injected DCs from the dermis to the draining lymph nodes (dLN). Laser illumination also slightly but significantly enhanced the expression of costimulatory molecule CD80 and MHC I on inoculated DCs. As a result, more vigorous expansion of tumor-specific IFN-gamma(+)CD8(+) T lymphocytes and enhanced CTL activity against 4T1 but not irrelevant tumor cells were obtained in the laser-treated group over the control group. Laser-augmented DC immunization also completely abrogated early growth of 4T1 tumor and B16F10 melanoma in preventive tumor models and significantly extended the survival of 4T1-resected mice in a therapeutic tumor model. Conclusion: These data suggest a simple, safe, laser-based approach to significantly enhance DC-based immunotherapy. Clin Cancer Res; 18(8); 2240-9. (C) 2012 AACR. C1 [Chen, Xinyuan; Zeng, Qiyan; Wu, Mei X.] Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Sch Med,Dept Dermatol, Boston, MA 02114 USA. [Wu, Mei X.] Harvard MIT Div Hlth Sci & Technol HST, Cambridge, MA USA. RP Wu, MX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Sch Med,Dept Dermatol, 50 Blossom St,Edwards 222, Boston, MA 02114 USA. EM mwu2@partners.org FU NIH [AI070785, RC1 DA028378]; Bill and Melinda Gates Foundation [53273] FX This work was supported in part by the NIH grants AI070785 and RC1 DA028378 and Grand Challenges Explorations grant # 53273 from the Bill and Melinda Gates Foundation (to M. X. Wu). NR 35 TC 8 Z9 8 U1 0 U2 7 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 APR 15 PY 2012 VL 18 IS 8 BP 2240 EP 2249 DI 10.1158/1078-0432.CCR-11-2654 PG 10 WC Oncology SC Oncology GA 927KW UT WOS:000302907300015 PM 22392913 ER PT J AU Liao, XY Morikawa, T Lochhead, P Imamura, Y Kuchiba, A Yamauchi, M Nosho, K Qian, ZR Nishihara, R Meyerhardt, JA Fuchs, CS Ogino, S AF Liao, Xiaoyun Morikawa, Teppei Lochhead, Paul Imamura, Yu Kuchiba, Aya Yamauchi, Mai Nosho, Katsuhiko Qian, Zhi Rong Nishihara, Reiko Meyerhardt, Jeffrey A. Fuchs, Charles S. Ogino, Shuji TI Prognostic Role of PIK3CA Mutation in Colorectal Cancer: Cohort Study and Literature Review SO CLINICAL CANCER RESEARCH LA English DT Review ID ISLAND METHYLATOR PHENOTYPE; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; PAPILLARY THYROID-CARCINOMA; POPULATION-BASED SAMPLE; COLON-CANCER; MICROSATELLITE INSTABILITY; BRAF MUTATION; POOR-PROGNOSIS; GENE-MUTATIONS; SURVIVAL AB Purpose: Mutations in PIK3CA [the gene encoding the p110a catalytic subunit of phosphatidylinositide-3-kinase (PI3K)] play an important role in colorectal carcinogenesis. Experimental evidence suggests that PIK3CA exon 9 and exon 20 mutations trigger different biologic effects, and that concomitant mutations in both exons 9 and 20 synergistically enhance tumorigenic effects. Thus, we hypothesized that PIK3CA exon 9 and exon 20 mutations might have differential effects on clinical outcome in colorectal cancer, and that concomitant PIK3CA exon 9 and 20 mutations might confer aggressive tumor behavior. Experimental Design: We sequenced PIK3CA by pyrosequencing in 1,170 rectal and colon cancers in two prospective cohort studies, and found 189 (16%) PIK3CA mutated tumors. Mortality HR according to PIK3CA status was computed using Cox proportional hazards model, adjusting for clinical and molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and BRAF and KRAS mutations. Results: Compared with PIK3CA wild-type cases, patients with concomitant PIK3CA mutations in exons 9 and 20 experienced significantly worse cancer-specific survival [log-rank P = 0.031; multivariate HR = 3.51; 95% confidence interval (CI): 1.28-9.62] and overall survival (log-rank P = 0.0008; multivariate HR = 2.68; 95% CI: 1.24-5.77). PIK3CA mutation in either exon 9 or 20 alone was not significantly associated with patient survival. No significant interaction of PIK3CA mutation with BRAF or KRAS mutation was observed in survival analysis. Conclusion: Coexistence of PIK3CA (the PI3K p110a subunit) exon 9 and 20 mutations, but not PIK3CA mutation in either exon 9 or 20 alone, is associated with poor prognosis of colorectal cancer patients. Clin Cancer Res; 18(8); 2257-68. (C) 2012 AACR. C1 [Ogino, Shuji] Harvard Univ, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Brigham & Womens Hosp,Sch Med,Dept Med Oncol, Boston, MA 02215 USA. [Fuchs, Charles S.] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02215 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Nosho, Katsuhiko] Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. RP Ogino, S (reprint author), Harvard Univ, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Brigham & Womens Hosp,Sch Med,Dept Med Oncol, 450 Brookline Ave,Room JF 215C, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu OI Qian, Zhi rong/0000-0003-1633-4120 FU U.S. NIH [P01CA87969, P01CA55075, P50CA127003, R01CA151993]; Bennett Family Fund for Targeted Therapies Research; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance FX This work was supported by U.S. NIH [P01CA87969 (to S. E. Hankinson), P01CA55075 (to W. C. Willett), P50CA127003 (to C. S. Fuchs), and R01CA151993 (to S. Ogino)]; the Bennett Family Fund for Targeted Therapies Research; and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. NR 50 TC 122 Z9 123 U1 3 U2 28 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 APR 15 PY 2012 VL 18 IS 8 BP 2257 EP 2268 DI 10.1158/1078-0432.CCR-11-2410 PG 12 WC Oncology SC Oncology GA 927KW UT WOS:000302907300017 PM 22357840 ER PT J AU Hock, H AF Hock, Hanno TI A complex Polycomb issue: the two faces of EZH2 in cancer SO GENES & DEVELOPMENT LA English DT Article DE T-ALL; EZH2; PRC2; leukemia; JARID2; DNMT3A ID DEMETHYLASE JMJD3 CONTRIBUTES; METHYLTRANSFERASE GENE EZH2; CHROMATIN REMODELING GENES; GROUP PROTEIN EZH2; B-CELL LYMPHOMAS; STEM-CELLS; H3K27ME3 DEMETHYLASE; SOMATIC MUTATIONS; MYELODYSPLASTIC SYNDROMES; MYELOID MALIGNANCIES AB In the April 1, 2012, issue of Genes & Development, Simon and colleagues (pp. 651-656) demonstrated that the disruption of Ezh2 in mice is sufficient to cause T-acute lymphoblastic leukemia (T-ALL). Moreover, in concert with concurrent studies, the authors revealed that similar mechanisms are involved in human T-ALL. These data contrast with previous findings showing that increased EZH2 activity promotes cancer. C1 [Hock, Hanno] Massachusetts Gen Hosp, Ctr Canc, Ctr Regenerat Med, Boston, MA 02114 USA. [Hock, Hanno] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Hock, Hanno] Harvard Univ, Sch Med, Boston, MA 02138 USA. RP Hock, H (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Regenerat Med, Boston, MA 02114 USA. EM hock.hanno@mgh.harvard.edu FU Federal Share of the Program Income; Massachusetts General Hospital [C06 CA059267]; Proton Therapy Research and Treatment Center FX I thank Dr. Charles Roberts (DFCI) for insightful ideas. This work was supported by the Federal Share of the Program Income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 46 TC 56 Z9 56 U1 4 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 2012 VL 26 IS 8 BP 751 EP 755 DI 10.1101/gad.191163.112 PG 5 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 927LR UT WOS:000302909600003 PM 22508723 ER PT J AU Dunn, GP Rinne, ML Wykosky, J Genovese, G Quayle, SN Dunn, IF Agarwalla, PK Chheda, MG Campos, B Wang, A Brennan, C Ligon, KL Furnari, F Cavenee, WK Depinho, RA Chin, L Hahn, WC AF Dunn, Gavin P. Rinne, Mikael L. Wykosky, Jill Genovese, Giannicola Quayle, Steven N. Dunn, Ian F. Agarwalla, Pankaj K. Chheda, Milan G. Campos, Benito Wang, Alan Brennan, Cameron Ligon, Keith L. Furnari, Frank Cavenee, Webster K. Depinho, Ronald A. Chin, Lynda Hahn, William C. TI Emerging insights into the molecular and cellular basis of glioblastoma SO GENES & DEVELOPMENT LA English DT Review DE glioblastoma; invasion; angiogenesis; tumor-initiating cells; IDH1; glioma classification ID GROWTH-FACTOR-RECEPTOR; STEM-LIKE CELLS; ISOCITRATE DEHYDROGENASE 1; CENTRAL-NERVOUS-SYSTEM; ACUTE MYELOID-LEUKEMIA; NEURAL STEM/PROGENITOR CELLS; BEVACIZUMAB PLUS IRINOTECAN; INTEGRATED GENOMIC ANALYSIS; RECURRENT MALIGNANT GLIOMA; TUMOR-INITIATING CELLS AB Glioblastoma is both the most common and lethal primary malignant brain tumor. Extensive multiplatform genomic characterization has provided a higher-resolution picture of the molecular alterations underlying this disease. These studies provide the emerging view that "glioblastoma'' represents several histologically similar yet molecularly heterogeneous diseases, which influences taxonomic classification systems, prognosis, and therapeutic decisions. C1 [Dunn, Gavin P.; Rinne, Mikael L.; Genovese, Giannicola; Quayle, Steven N.; Agarwalla, Pankaj K.; Chheda, Milan G.; Hahn, William C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Mol & Cellular Oncol,Dept Med Oncol, Boston, MA 02115 USA. [Dunn, Gavin P.; Agarwalla, Pankaj K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Dunn, Gavin P.; Rinne, Mikael L.; Agarwalla, Pankaj K.; Chheda, Milan G.; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Rinne, Mikael L.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Wykosky, Jill; Furnari, Frank; Cavenee, Webster K.] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Dunn, Ian F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Chheda, Milan G.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, Dept Neurol, New York, NY 10065 USA. [Campos, Benito] Univ Heidelberg, Dept Neurosurg, Heidelberg, Germany. [Wang, Alan; Depinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Brennan, Cameron] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, Dept Neurosurg, New York, NY 10065 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02215 USA. [Furnari, Frank] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Genom Med, Houston, TX 77030 USA. RP Hahn, WC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Mol & Cellular Oncol,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu RI Waha, Andreas/J-2950-2014; OI Brennan, Cameron/0000-0003-4064-8891 FU NIH [PO1 CA117969, RC2 CA148268, PO1 CA142536, P01 CA95616, NCI-MMHCC-CA84313-06, K08-NS062907]; Ben and Catherine Ivy Foundation; Goldhirsh Foundation; NIH (NINDS) [F32 NS066519]; Sontag Foundation; ABTA; NINDS; Brain Science Foundation FX We thank Tanaz Sharifinia and Ravindra Uppaluri for comments on the manuscript. This work was supported by NIH Grants PO1 CA117969, RC2 CA148268, and PO1 CA142536 (to W.C.H., K.L., L.C., and R.A.D.); the Ben and Catherine Ivy Foundation (to L.C., R.A.D., and K.L.); an award from the Goldhirsh Foundation (to F.F. and K.L.); NIH (NINDS) Fellowship Award F32 NS066519 (to J.W.); NIH Grant P01 CA95616 (to C.B, K.L., L.C., W.C.H., W.K.C., F.F., and R.A.D.); NIH Grant NCI-MMHCC-CA84313-06 to L.C. and R.A.D.); NIH Grant K08-NS062907 (to M.G.C.); an award from the Sontag Foundation (to K.L.); an ABTA Basic Research Fellowship (to G.P.D.); NINDS R25 award (to G.P.D.); and the Brain Science Foundation (to I.F.D.). W.K.C. is a fellow of the National Foundation for Cancer Research. NR 360 TC 179 Z9 187 U1 5 U2 41 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 2012 VL 26 IS 8 BP 756 EP 784 DI 10.1101/gad.187922.112 PG 29 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 927LR UT WOS:000302909600004 PM 22508724 ER PT J AU Kelly, PJ Lin, NU Claus, EB Quant, EC Weiss, SE Alexander, BM AF Kelly, Paul J. Lin, Nancy U. Claus, Elizabeth B. Quant, Eudocia C. Weiss, Stephanie E. Alexander, Brian M. TI Salvage stereotactic radiosurgery for breast cancer brain metastases SO CANCER LA English DT Article DE salvage; stereotactic radiosurgery; breast cancer; brain metastases; radiation ID NERVOUS-SYSTEM METASTASES; RADIATION-THERAPY; CEREBRAL METASTASES; CLINICAL-OUTCOMES; SUBTYPES; RADIOTHERAPY; SURVIVAL; TUMORS; WOMEN; TRIAL AB BACKGROUND: Salvage stereotactic radiosurgery (SRS) is often considered in breast cancer patients previously treated for brain metastases. The goal of this study was to analyze clinical outcomes and prognostic factors for survival in the salvage setting. METHODS: The authors retrospectively examined 79 consecutive breast cancer patients who received salvage SRS (interval of > 3 months after initial therapy), 76 of whom (96%) received prior whole-brain radiation therapy. Overall survival (OS) and central nervous system (CNS) progression-free survival rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. RESULTS: Median age was 50.5 years. Fifty-eight percent of this population was estrogen receptor positive, 62% was HER2 positive, and 10% was triple negative. At the time of SRS, 95% had extracranial metastases, with 81% of extracranial metastases at other visceral sites (lung/ pleura/ liver). Forty-eight percent had stable extracranial disease. Median interval from initial brain metastases therapy to SRS was 8.4 months. Median CNS progression- free survival after SRS was 5.7 months (interquartile range [ IQR], 3.6-11 months), and median OS was 9.8 months (IQR, 3.8-18 months). Eighty-two percent of evaluable patients received further systemic therapy after SRS. HER2 status (adjusted hazard ratio [ HR], 2.4; P.008) and extracranial disease status (adjusted HR, 2.7; P.004) were significant prognostic factors for survival on multivariate analysis. CONCLUSIONS: In patients with good Karnofsky performance status, salvage SRS for breast cancer brain metastases is a reasonable treatment option, given an associated median survival in excess of 9 months. Furthermore, patients with HER2-positive tumors at diagnosis or stable extracranial disease at the time of SRS have an improved clinical course, with median survival of > 1 year. Cancer 2012; 118: 2014-20. (C) 2011 American Cancer Society. C1 [Kelly, Paul J.; Weiss, Stephanie E.; Alexander, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Kelly, Paul J.; Lin, Nancy U.; Claus, Elizabeth B.; Quant, Eudocia C.; Weiss, Stephanie E.; Alexander, Brian M.] Harvard Univ, Sch Med, Boston, MA USA. [Lin, Nancy U.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Claus, Elizabeth B.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Claus, Elizabeth B.] Yale Univ, Sch Med, New Haven, CT USA. [Quant, Eudocia C.] Dana Farber Brigham & Womens Ctr, Dept Neurol, Boston, MA USA. RP Kelly, PJ (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1,L2, Boston, MA 02115 USA. EM paulj.kelly@hse.ie FU Breast Cancer Research Foundation; Susan G. Komen Foundation [BCTR0600849] FX This study was supported by the Breast Cancer Research Foundation and the Susan G. Komen Foundation grant BCTR0600849. NR 25 TC 13 Z9 13 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 15 PY 2012 VL 118 IS 8 BP 2014 EP 2020 DI 10.1002/cncr.26343 PG 7 WC Oncology SC Oncology GA 922JQ UT WOS:000302543600008 PM 21918959 ER PT J AU Lowry, KP Lee, JM Kong, CY McMahon, PM Gilmore, ME Chubiz, JEC Pisano, ED Gatsonis, C Ryan, PD Ozanne, EM Gazelle, GS AF Lowry, Kathryn P. Lee, Janie M. Kong, Chung Y. McMahon, Pamela M. Gilmore, Michael E. Chubiz, Jessica E. Cott Pisano, Etta D. Gatsonis, Constantine Ryan, Paula D. Ozanne, Elissa M. Gazelle, G. Scott TI Annual screening strategies in BRCA1 and BRCA2 gene mutation carriers SO CANCER LA English DT Article DE BRCA1 gene; BRCA2 gene; breast neoplasms; mass screening; computer simulation ID SERVICES TASK-FORCE; HIGH FAMILIAL RISK; BREAST-CANCER; FILM MAMMOGRAPHY; COST-EFFECTIVENESS; WOMEN; SURVEILLANCE; RADIATION; PREDISPOSITION; METAANALYSIS AB BACKGROUND: Although breast cancer screening with mammography and magnetic resonance imaging (MRI) is recommended for breast cancer-susceptibility gene (BRCA) mutation carriers, there is no current consensus on the optimal screening regimen. METHODS: The authors used a computer simulation model to compare 6 annual screening strategies (film mammography [FM], digital mammography [DM], FM and magnetic resonance imaging [MRI] or DM and MRI contemporaneously, and alternating FM/ MRI or DM/ MRI at 6-month intervals) beginning at ages 25 years, 30 years, 35 years, and 40 years, and 2 strategies of annual MRI with delayed alternating DM/ FM versus clinical surveillance alone. Strategies were evaluated without and with mammography-induced breast cancer risk using 2 models of excess relative risk. Input parameters were obtained from the medical literature, publicly available databases, and calibration. RESULTS: Without radiation risk effects, alternating DM/ MRI starting at age 25 years provided the highest life expectancy (BRCA1, 72.52 years, BRCA2, 77.63 years). When radiation risk was included, a small proportion of diagnosed cancers was attributable to radiation exposure (BRCA1, < 2%; BRCA2, < 4%). With radiation risk, alternating DM/ MRI at age 25 years or annual MRI at age 25 years/ delayed alternating DM at age 30 years was the most effective, depending on the radiation risk model used. Alternating DM/ MRI starting at age 25 years also produced the highest number of false-positive screens per woman (BRCA1, 4.5 BRCA2, 8.1). CONCLUSIONS: Annual MRI at age 25 years/ delayed alternating DM at age 30 years is probably the most effective screening strategy in BRCA mutation carriers. Screening benefits, associated risks, and personal acceptance of false-positive results should be considered in choosing the optimal screening strategy for individual women. Cancer 2012; 118: 2021-30. VC 2011 American Cancer Society. C1 [Lowry, Kathryn P.; Lee, Janie M.; Kong, Chung Y.; McMahon, Pamela M.; Gilmore, Michael E.; Chubiz, Jessica E. Cott; Ozanne, Elissa M.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Lowry, Kathryn P.; Lee, Janie M.; Kong, Chung Y.; McMahon, Pamela M.; Ozanne, Elissa M.; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA USA. [Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Pisano, Etta D.] Med Univ S Carolina, Coll Med, Charleston, SC 29425 USA. [Gatsonis, Constantine] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Ryan, Paula D.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. RP Lee, JM (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St 10th Floor, Boston, MA 02114 USA. EM janie@mgh-ita.org FU Harvard Medical School Office for Enrichment Programming; National Institutes of Health (NIH) [K07CA128816, K25CA133141, R00CA126147]; American Cancer Society [MRSG112037] FX This work was supported by in part by the following grants and organizations: Harvard Medical School Office for Enrichment Programming (K. P. L.), National Institutes of Health (NIH) grant K07CA128816 (J.M.L.), NIH grant K25CA133141 (C.Y.K.), NIH grant R00CA126147 (P. M. M.), and American Cancer Society grant MRSG112037 (E.M.O.). NR 30 TC 32 Z9 32 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 15 PY 2012 VL 118 IS 8 BP 2021 EP 2030 DI 10.1002/cncr.26424 PG 10 WC Oncology SC Oncology GA 922JQ UT WOS:000302543600009 PM 21935911 ER PT J AU Binkley, JM Harris, SR Levangie, PK Pearl, M Guglielmino, J Kraus, V Rowden, D AF Binkley, Jill M. Harris, Susan R. Levangie, Pamela K. Pearl, Marcia Guglielmino, Janine Kraus, Valerie Rowden, Diana TI Patient perspectives on breast cancer treatment side effects and the prospective surveillance model for physical rehabilitation for women with breast cancer SO CANCER LA English DT Article DE breast cancer; patient perspectives; treatment side effects; lymphedema; fatigue; shoulder dysfunction; rehabilitation; exercise ID QUALITY-OF-LIFE; PREOPERATIVE ASSESSMENT ENABLES; LONG-TERM MORBIDITY; SHOULDER FUNCTION; CONTROLLED-TRIAL; EARLY-DIAGNOSIS; BODY-IMAGE; BONE LOSS; 1ST YEAR; LYMPHEDEMA AB Women's experience of breast cancer is complex, affecting all aspects of life during and after treatment. Patients' perspectives about common impairments and functional limitations secondary to breast cancer treatment, including upper extremity motion restriction, lymphedema, fatigue, weight gain, pain, and chemotherapy-induced peripheral neuropathy, are addressed. Women often report being uninformed regarding these side effects and surprised that they do not always disappear after treatment, but remain part of their lives. Breast cancer patients express strong, unmet needs for education, information, and intervention for these side effects. Evidence suggests that rehabilitation and exercise are effective in preventing and managing many physical side effects of breast cancer treatment. Nevertheless, few women are referred to rehabilitation during or after treatment, and fewer receive baseline assessments of impairment and function to facilitate early detection of impairment and functional limitations. The prospective surveillance model of rehabilitation will serve the needs of women with breast cancer by providing education and information about treatment side effects, reducing the incidence and burden of side effects through early identification and treatment, and enhancing access to timely rehabilitation. Integration of exercise as a component of the model benefits patients at every phase of survivorship, by addressing individual concerns about exercise during and after treatment and highlighting the important contribution of exercise to overall health and survival. The prospective surveillance model of rehabilitation can meet the evident and often expressed needs of survivors for information, guidance, and interventionthus addressing, and potentially improving, overall quality of life for individuals diagnosed with and treated for breast cancer. Cancer 2012;. (c) 2012 American Cancer Society. C1 [Binkley, Jill M.; Pearl, Marcia] TurningPoint Womens Healthcare, Alpharetta, GA 30022 USA. [Harris, Susan R.] Univ British Columbia, Dept Phys Therapy, Vancouver, BC V5Z 1M9, Canada. [Levangie, Pamela K.] Massachusetts Gen Hosp, Inst Hlth Profess, Phys Therapy Program, Boston, MA 02114 USA. [Guglielmino, Janine; Kraus, Valerie] Living Breast Canc, Haverford, PA USA. [Rowden, Diana] Susan G Komen Cure, Dallas, TX USA. RP Binkley, JM (reprint author), TurningPoint Womens Healthcare, 11180 State Bridge Rd,Suite 503, Alpharetta, GA 30022 USA. EM jbinkley@myturningpoint.org OI Harris, Susan R/0000-0003-2679-6548 FU American Cancer Society, through the Longaberger Company(R); Longaberger Horizon of Hope(R) Campaign FX Support for this meeting and supplement was provided by the American Cancer Society, through the Longaberger Company (R), a direct selling company offering home products including hand-crafted baskets made in Ohio, and the Longaberger Horizon of Hope (R) Campaign, which provided a grant to the American Cancer Society for breast cancer research and education. NR 100 TC 42 Z9 44 U1 2 U2 30 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 15 PY 2012 VL 118 SU 8 BP 2207 EP 2216 DI 10.1002/cncr.27469 PG 10 WC Oncology SC Oncology GA 922JV UT WOS:000302544100004 PM 22488695 ER PT J AU Dangi, A Sumpter, TL Kimura, S Stolz, DB Murase, N Raimondi, G Vodovotz, Y Huang, C Thomson, AW Gandhi, CR AF Dangi, Anil Sumpter, Tina L. Kimura, Shoko Stolz, Donna B. Murase, Noriko Raimondi, Giorgio Vodovotz, Yoram Huang, Chao Thomson, Angus W. Gandhi, Chandrashekhar R. TI Selective Expansion of Allogeneic Regulatory T Cells by Hepatic Stellate Cells: Role of Endotoxin and Implications for Allograft Tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SINUSOIDAL ENDOTHELIAL-CELLS; RAT-LIVER TRANSPLANTATION; ANTIGEN-PRESENTING CELLS; DENDRITIC CELLS; ISCHEMIA/REPERFUSION INJURY; KUPFFER CELLS; IN-VIVO; RETINOIC ACID; DNA-SYNTHESIS; ACTIVATION AB Hepatic stellate cells (HSCs) may play an important role in hepatic immune regulation by producing numerous cytokines/chemokines and expressing Ag-presenting and T cell coregulatory molecules. Due to disruption of the endothelial barrier during cold-ischemic storage and reperfusion of liver grafts, HSCs can interact directly with cells of the immune system. Endotoxin (LPS), levels of which increase in liver diseases and transplantation, stimulates the synthesis of many mediators by HSCs. We hypothesized that LPS-stimulated HSCs might promote hepatic tolerogenicity by influencing naturally occurring immunosuppressive CD4(+) CD25(+)Foxp3(+) regulatory T cells (Tregs). Following their portal venous infusion, allogeneic CD4(+) T cells, including Tregs, were found closely associated with HSCs, and this association increased in LPS-treated livers. In vitro, both unstimulated and LPS-stimulated HSCs upregulated Fas (CD95) expression on conventional CD4(+) T cells and induced their apoptosis in a Fas/Fas ligand-dependent manner. By contrast, HSCs induced Treg proliferation, which required cell-cell contact and was MHC class II-dependent. This effect was augmented when HSCs were pretreated with LPS. LPS increased the expression of MHC class II, CD80, and CD86 and stimulated the production of IL-1 alpha, IL-1 beta, IL-6, IL-10 and TNF-alpha by HSCs. Interestingly, production of IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha was strongly inhibited, but that of IL-10 enhanced in LPS-pretreated HSC/Treg cocultures. Adoptively transferred allogeneic HSCs migrated to the secondary lymphoid tissues and induced Treg expansion in lymph nodes. These data implicate endotoxin-stimulated HSCs as important immune regulators in liver transplantation by inducing selective expansion of tolerance-promoting Tregs and reducing inflammation and alloimmunity. The Journal of Immunology, 2012, 188: 3667-3677. C1 [Dangi, Anil; Kimura, Shoko; Murase, Noriko; Raimondi, Giorgio; Huang, Chao; Thomson, Angus W.; Gandhi, Chandrashekhar R.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Dept Surg, Pittsburgh, PA 15213 USA. [Sumpter, Tina L.] Univ Pittsburgh, Dept Dermatol, Pittsburgh, PA 15213 USA. [Stolz, Donna B.] Univ Pittsburgh, Dept Cell Biol, Pittsburgh, PA 15213 USA. [Thomson, Angus W.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15213 USA. [Gandhi, Chandrashekhar R.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. [Gandhi, Chandrashekhar R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Gandhi, CR (reprint author), Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Dept Surg, E-1540 BST,200 Lothrop St, Pittsburgh, PA 15213 USA. EM Gandhics@msx.upmc.edu FU National Institutes of Health [PO1A1081678, DK071753]; American Diabetes Association; Joseph A. Patrick Research Fellowship in Transplantation; Clinical and Translational Science Institute; National Center for Research Resources [UL1 RR024153]; American Society of Transplantation FX This work was supported by National Institutes of Health Grant PO1A1081678. G. R. is supported by a Junior Faculty Grant from the American Diabetes Association, a Joseph A. Patrick Research Fellowship in Transplantation, and a Clinical and Translational Science Institute Pilots to Expand Investigator Repertoire grant (funded through Grant UL1 RR024153 from the National Center for Research Resources). T. L. S. was the recipient of an American Society of Transplantation Basic Science Fellowship. S. K. is supported by National Institutes of Health Grant DK071753. NR 77 TC 31 Z9 33 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2012 VL 188 IS 8 BP 3667 EP 3677 DI 10.4049/jimmunol.1102460 PG 11 WC Immunology SC Immunology GA 923TD UT WOS:000302641400013 PM 22427640 ER PT J AU Sage, PT Varghese, LM Martinelli, R Sciuto, TE Kamei, M Dvorak, AM Springer, TA Sharpe, AH Carman, CV AF Sage, Peter T. Varghese, Laya M. Martinelli, Roberta Sciuto, Tracey E. Kamei, Masataka Dvorak, Ann M. Springer, Timothy A. Sharpe, Arlene H. Carman, Christopher V. TI Antigen Recognition Is Facilitated by Invadosome-like Protrusions Formed by Memory/Effector T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; IMMUNOLOGICAL SYNAPSES; TRANSENDOTHELIAL MIGRATION; IN-VIVO; TRANSCELLULAR DIAPEDESIS; RECEPTOR MICROCLUSTERS; ACTIN CYTOSKELETON; IMMUNE SYNAPSE; KILLER-CELLS; ACTIVATION AB Adaptive immunity requires that T cells efficiently scan diverse cell surfaces to identify cognate Ag. However, the basic cellular mechanisms remain unclear. In this study, we investigated this process using vascular endothelial cells, APCs that possess a unique and extremely advantageous, planar morphology. High-resolution imaging revealed that CD4 memory/effector T cells dynamically probe the endothelium by extending submicron-scale, actin-rich "invadosome/podosome-like protrusions" (ILPs). The intimate intercellular contacts enforced by ILPs consistently preceded and supported T cell activation in response to endothelial MHC class II/Ag. The resulting calcium flux stabilized dense arrays of ILPs (each enriched in TCR, protein kinase C-theta, ZAP70, phosphotyrosine, and HS1), forming what we term a podo-synapse. Similar findings were made using CD8 CTLs on endothelium. Furthermore, careful re-examination of both traditional APC models and professional APCs suggests broad relevance for ILPs in facilitating Ag recognition. Together, our results indicate that ILPs function as sensory organelles that serve as actuators of immune surveillance. The Journal of Immunology, 2012, 188: 3686-3699. C1 [Sage, Peter T.; Varghese, Laya M.; Martinelli, Roberta; Kamei, Masataka; Carman, Christopher V.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Ctr Vasc Biol Res, Boston, MA 02215 USA. [Sage, Peter T.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Sciuto, Tracey E.; Dvorak, Ann M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol,Ctr Vasc Biol Res, Boston, MA 02215 USA. [Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. RP Carman, CV (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Ctr Vasc Biol Res, 330 Brookline Ave,RN234, Boston, MA 02215 USA. EM ccarman@bidmc.harvard.edu RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU National Institutes of Health [T32 AI070085, AI078897, HL04006]; American Heart Association; Arthritis Foundation; Roche Organ Transplant Research Foundation FX This work was supported by the National Institutes of Health (Grants T32 AI070085 to P. T. S., AI078897 to A. H. S., and HL04006 to C. V. C.) and the American Heart Association, the Arthritis Foundation, and the Roche Organ Transplant Research Foundation (to C.V.C.). NR 81 TC 35 Z9 35 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2012 VL 188 IS 8 BP 3686 EP 3699 DI 10.4049/jimmunol.1102594 PG 14 WC Immunology SC Immunology GA 923TD UT WOS:000302641400015 PM 22442443 ER PT J AU Li, DW Zhao, HY Kranzler, HR Oslin, D Anton, RF Farrer, LA Gelernter, J AF Li, Dawei Zhao, Hongyu Kranzler, Henry R. Oslin, David Anton, Raymond F. Farrer, Lindsay A. Gelernter, Joel TI Association of COL25A1 with Comorbid Antisocial Personality Disorder and Substance Dependence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Addiction; amyloid plaque; antisocial personality disorder (ASPD); association; collagen XXV alpha 1 (COL25A1); substance dependence ID MULTILOCUS GENOTYPE DATA; ALZHEIMERS-DISEASE; DRUG-DEPENDENCE; CANDIDATE GENES; POPULATION; BEHAVIOR; STRATIFICATION; FREQUENCIES; ALCOHOLISM; INFERENCE AB Background: Antisocial personality disorder (ASPD) is a psychiatric disorder characterized by a long-term pattern of manipulating, exploiting, or violating the rights of others. Methods: Subjects ascertained for genetic studies of substance dependence (SD) and diagnosed with ASPD and comorbid SD were included in a two-stage genetic association study. In the discovery stage, 627 single nucleotide polymorphisms (SNPs) located in 179 candidate genes for addiction were analyzed in a case-control cohort and family-based cohort. The significant findings were replicated in an independent case-control cohort. Results: One SNP, rs13134663, in the collagen XXV alpha 1 gene (COL25A1) was significantly associated with ASPD in both African Americans and European Americans (smallest p values were .0002 and .0004, respectively). There was also evidence of association with the same SNP in independent samples of African American and European American cases and control subjects (p = .035 and .033, respectively). Analysis of the combined set of case-control subjects yielded an allelic p value of 9 x 10(-6) with odds ratio (95% confidence interval) of 1.3 (1.16, 1.47) (smallest p = 1 x 10(-7); Bonferroni threshold p = .00012). Conclusions: The COL25A1 gene, located at chromosome 4q25, encodes the collagen-like Alzheimer amyloid plaque component precursor, a type II transmembrane protein specifically expressed in neurons; it co-localizes with amyloid beta in senile plaques in Alzheimer disease brains. This SNP maps to the transcription factor binding site and is conserved in 17 vertebrates, including mice and rats. Our findings suggest that COL25A1 may be associated with ASPD, especially in the context of SD. C1 [Gelernter, Joel] Yale Univ, Dept Psychiat, Sch Med, Vet Affairs Connecticut Healthcare Ctr, West Haven, CT 06516 USA. [Zhao, Hongyu] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, West Haven, CT 06516 USA. [Zhao, Hongyu; Gelernter, Joel] Yale Univ, Dept Genet, Sch Med, West Haven, CT 06516 USA. [Kranzler, Henry R.; Oslin, David] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Kranzler, Henry R.; Oslin, David] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Vet Integrated Serv Network 4, Philadelphia, PA USA. [Anton, Raymond F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. RP Gelernter, J (reprint author), Yale Univ, Dept Psychiat, Sch Med, Vet Affairs Connecticut Healthcare Ctr, 950 Campbell Ave,116A2, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu RI Li, Dawei/A-3466-2011; OI Farrer, Lindsay/0000-0001-5533-4225 FU National Institutes of Health, United States [DA12849, DA12690, DA028909, AA017535, AA12870, AA11330]; National Institutes of Health [N01-HG-65403]; Alkermes; GlaxoSmithKline; Gilead; Lundbeck; Roche; Merck; Eli Lilly; Johnson Johnson; Hythiam Inc.; Alcohol Clinical Trials Initiative FX This work was supported by the research Grants DA12849, DA12690, DA028909, AA017535, AA12870, and AA11330 from the National Institutes of Health, United States. Genotyping services were provided by the Center for Inherited Disease Research. The Center for Inherited Disease Research is fully funded through a Federal contract from the National Institutes of Health to The Johns Hopkins University (contract number N01-HG-65403).; Dr. Kranzler has been a paid consultant for Alkermes, GlaxoSmithKline, Gilead, Lundbeck, and Roche. He has received research support from Merck. Dr. Anton has received honoraria or grant support from Eli Lilly, Johnson & Johnson, Alkermes, GlaxoSmithKline, Merck, and Hythiam Inc. Drs. Kranzler and Anton also report associations with Eli Lilly, Janssen, Schering Plough, Lundbeck, Alkermes, GlaxoSmithKline, Abbott, and Johnson & Johnson, as these companies provide support to the American College of Neuropsychopharmacology Alcohol Clinical Trials Initiative and both receive support from the Alcohol Clinical Trials Initiative. The other authors reported no biomedical financial interests or potential conflicts of interest. NR 38 TC 9 Z9 9 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2012 VL 71 IS 8 BP 733 EP 740 DI 10.1016/j.biopsych.2011.12.011 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 921GA UT WOS:000302464900015 PM 22297151 ER PT J AU Ware, NC Wyatt, MA Haberer, JE Baeten, JM Kintu, A Psaros, C Safren, S Tumwesigye, E Celum, CL Bangsberg, DR AF Ware, Norma C. Wyatt, Monique A. Haberer, Jessica E. Baeten, Jared M. Kintu, Alexander Psaros, Christina Safren, Steven Tumwesigye, Elioda Celum, Connie L. Bangsberg, David R. TI What's Love Got to Do With It? Explaining Adherence to Oral Antiretroviral Pre-Exposure Prophylaxis for HIV-Serodiscordant Couples SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adherence; HIV prevention; HIV-serodiscordant couples; HIV acquisition; pre-exposure prophylaxis; PrEP AB Objective: Adherence may be the "Achilles heel" of pre-exposure prophylaxis (PrEP), a promising biomedical approach to HIV prevention. This article presents an explanation of PrEP adherence for African serodiscordant couples derived from qualitative data. Design: Explaining quantitative findings is one way qualitative investigation contributes to research in medicine and public health. This qualitative interview study was nested in the Partners PrEP Study, a phase III randomized trial evaluating oral tenofovir and emtricitabine/tenofovir PrEP to prevent HIV acquisition by HIV-uninfected partners in serodiscordant heterosexual couples. Methods: In-depth qualitative interviews were provided by 60 Partners PrEP Study participants in Uganda. Interviews used open-ended questions eliciting information on adherence experiences, barriers, and facilitators. An inductive approach informed by grounded theory methodology was used to analyze study data. Results: The proposed explanation may be summarized as follows. Serodiscordance destabilizes couples, as the HIV-negative partner reacts with anger, fear, and sadness to the implication of infidelity represented by HIV infection. A "discordance dilemma" ensues, as the desire to avoid acquiring HIV and the advantages of preserving the relationship become competing priorities. PrEP is seen as a solution-a means of safeguarding health without ending the relationship. PrEP users benefit from the support of partners, who reinforce adherence. Where discord in the relationship persists, adherence suffers. Conclusions: PrEP adherence in serodiscordant couples may be understood as a function of the desire to reduce risk although preserving a partnered relationship. PrEP use in stable couples may be associated with improved adherence and thus, greater effectiveness. C1 [Ware, Norma C.; Wyatt, Monique A.; Bangsberg, David R.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Haberer, Jessica E.; Bangsberg, David R.] Massachusetts Gen Hosp, Dept Med, Ctr Global Hlth, Boston, MA 02114 USA. [Baeten, Jared M.; Celum, Connie L.] Univ Washington, Dept Med, Dept Global Hlth, Seattle, WA USA. [Kintu, Alexander; Tumwesigye, Elioda] Kabwohe Clin Res Ctr, Kabwohe, Uganda. [Psaros, Christina; Safren, Steven] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Celum, Connie L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Ware, NC (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, 641 Huntington Ave, Boston, MA 02115 USA. EM norma_ware@hms.harvard.edu FU Bill and Melinda Gates Foundation FX Supported by a grant to D.R.B. from the Bill and Melinda Gates Foundation. NR 15 TC 90 Z9 91 U1 0 U2 18 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 APR 15 PY 2012 VL 59 IS 5 BP 463 EP 468 DI 10.1097/QAI.0b013e31824a060b PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 917BQ UT WOS:000302147400011 PM 22267018 ER PT J AU Panizzon, MS Fennema-Notestine, C Kubarych, TS Chen, CH Eyler, LT Fischl, B Franz, CE Grant, MD Hamza, S Jak, A Jernigan, TL Lyons, MJ Neale, MC Prom-Wormley, EC Seidman, L Tsuang, MT Wu, H Xian, H Dale, AM Kremen, WS AF Panizzon, Matthew S. Fennema-Notestine, Christine Kubarych, Thomas S. Chen, Chi-Hua Eyler, Lisa T. Fischl, Bruce Franz, Carol E. Grant, Michael D. Hamza, Samar Jak, Amy Jernigan, Terry L. Lyons, Michael J. Neale, Michael C. Prom-Wormley, Elizabeth C. Seidman, Larry Tsuang, Ming T. Wu, Hao Xian, Hong Dale, Anders M. Kremen, William S. TI Genetic and environmental influences of white and gray matter signal contrast: A new phenotype for imaging genetics? SO NEUROIMAGE LA English DT Article ID VIETNAM ERA TWIN; HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; LIKELIHOOD RATIO TESTS; SURFACE-BASED ANALYSIS; ALZHEIMERS-DISEASE; CORTICAL THICKNESS; HUMAN BRAIN; REGISTRY; MULTIVARIATE AB The estimation of cortical thickness is in part dependent on the degree of contrast in T1 signal intensity between white matter and gray matter along the cortical mantle. The ratio of white matter to gray matter signal (WM/GM contrast) has been found to vary as a function of age and Alzheimer's disease status, suggesting a biological component to what might otherwise be labeled as a nuisance variable. The aim of the present study was to determine if measures of WM/GM contrast are genetically influenced, as well as the degree to which this phenotype may be related to the genetic and environment determinants of cortical thickness. Participants were 514 male twins (130 monozygotic, 97 dizygotic pairs, and 60 unpaired individuals) from the Vietnam Era Twin Study of Aging. Ages ranged from 51 to 59 years. Measures of WM/GM contrast and cortical thickness were derived for 66 cortical regions of interest (ROI) using FreeSurfer-based methods. Univariate and bivariate twin analyses were used in order to estimate the heritability of WM/GM contrast, as well as the degree of shared genetic and environmental variance between WM/GM contrast and cortical thickness. WM/GM contrast was found to be significantly heritable in the majority of ROIs. The average heritability across individual ROls was highest in the occipital lobe (.50), and lowest in the cingulate cortex (.24). Significant phenotypic correlations between WM/GM contrast and cortical thickness were observed for most of the ROls. The majority of the phenotypic correlations were negative, ranging from -.11 to -.54. Of the 66 associations, only 17 significant genetic correlations were found, ranging from -.16 to -.34, indicating small amounts of shared genetic variance. The majority of the phenotypic correlations were accounted for by small unique environmental effects common between WM/GM contrast and cortical thickness. These findings demonstrate that like cortical thickness, WM/GM contrast is a genetically influenced brain structure phenotype. The lack of significant genetic correlations with cortical thickness suggests that this measure potentially represents a unique source of genetic variance, one that has yet to be explored by the field of imaging genetics. (C) 2012 Elsevier Inc. All rights reserved. C1 [Panizzon, Matthew S.; Fennema-Notestine, Christine; Chen, Chi-Hua; Eyler, Lisa T.; Franz, Carol E.; Hamza, Samar; Jak, Amy; Jernigan, Terry L.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Fennema-Notestine, Christine; Jernigan, Terry L.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Kubarych, Thomas S.; Neale, Michael C.; Prom-Wormley, Elizabeth C.; Wu, Hao] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Sch Med, Richmond, VA 23298 USA. [Eyler, Lisa T.; Jak, Amy] San Diego VA Hlth Care Syst, San Diego, CA 92161 USA. [Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Tsuang, Ming T.] Harvard Univ, Sch Med, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. [Fischl, Bruce] MIT, AI Lab, Cambridge, MA 02139 USA. [Grant, Michael D.; Lyons, Michael J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Jernigan, Terry L.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. [Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Sch Publ Hlth, Boston, MA 02115 USA. [Xian, Hong] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Kremen, William S.] VA Ctr Excellence Stress & Mental Hlth, San Diego, CA 92161 USA. RP Panizzon, MS (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,MC 0738, La Jolla, CA 92093 USA. EM mspanizz@ucsd.edu OI Prom-Wormley, Elizabeth/0000-0001-9230-9723; Lyons, Michael/0000-0001-6516-9219; Fennema-Notestine, Christine/0000-0002-6527-6361 FU National Institutes of Health/National Institute on Aging (NIH/NIA) [R01 AG18386, RO1 AG18384, RO1 AG22381, RO1 AG22982]; The U.S. Department of Veterans Affairs FX The VETSA project is supported by National Institutes of Health/National Institute on Aging (NIH/NIA) Grants R01 AG18386, RO1 AG18384, RO1 AG22381, and RO1 AG22982. The U.S. Department of Veterans Affairs has provided support for the development and maintenance of the Vietnam Era Twin Registry. Numerous organizations have provided invaluable assistance, including VA Cooperative Studies Program; VA Center of Excellence for Stress and Mental Health; Department of Defense; National Personnel Records Center, National Archives and Records Administration; the Internal Revenue Service; National Institutes of Health; National Opinion Research Center; National Research Council, National Academy of Sciences; the Institute for Survey Research, Temple University; Schulman, Ronca, and Bucuvalas, Inc. Most importantly, we gratefully acknowledge the cooperation and participation of the members of the Vietnam Era Twin Registry and their families. Without their contribution this research would not have been possible. NR 53 TC 14 Z9 14 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 APR 15 PY 2012 VL 60 IS 3 BP 1686 EP 1695 DI 10.1016/j.neuroimage.2012.01.122 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 917TZ UT WOS:000302202800010 PM 22500923 ER PT J AU Spitzer, TR AF Spitzer, Thomas R. TI Changing Stripes to Avoid Graft Versus Leukemia SO TRANSPLANTATION LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; MISMATCHED HLA C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Dept Med, 0 Emerson Pl,Suite 118, Boston, MA 02114 USA. EM tspitzer@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2012 VL 93 IS 7 BP 674 EP 675 DI 10.1097/TP.0b013e3182481154 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 916RZ UT WOS:000302122200007 PM 22456485 ER PT J AU Hsue, PY Scherzer, R Grunfeld, C Nordstrom, SM Schnell, A Kohl, LP Nitta, E Martin, JN Deeks, SG Weiss, EJ AF Hsue, Priscilla Y. Scherzer, Rebecca Grunfeld, Carl Nordstrom, Sarah M. Schnell, Amanda Kohl, Louis P. Nitta, Elaine Martin, Jeffrey N. Deeks, Steven G. Weiss, Ethan J. TI HIV Infection Is Associated With Decreased Thrombin Generation SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ANTIRETROVIRAL THERAPY; VENOUS THROMBOSIS; CELL-ACTIVATION; D-DIMER; INFLAMMATION; COAGULATION; BIOMARKERS; MARKERS; ADULTS; FRAM AB Background. Excess risk of cardiovascular disease occurs in effectively treated individuals with human immunodeficiency virus (HIV) infection. Although elevated plasma D-dimer levels are associated with increased morbidity and mortality, the impact of HIV infection on coagulation in vivo has not been well studied. Methods. We measured D-dimers, antithrombin, endogenous thrombin potential (ETP; a functional measure of thrombin generation in vitro), thrombin/antithrombin complexes (TAT; a measure of thrombin generation in vivo), tissue factor, prothrombin fragment 1 + 2 (F1+2), and normalized APC sensitivity ratio (nAPCsr) in 199 HIV-positive men who were receiving antiretroviral therapy and had an undetectable HIV RNA level, in 79 HIV-positive untreated men, and in 39 uninfected controls. Results. Median antithrombin levels were higher while the ETP was lower among HIV-infected adults (treated and untreated), compared with controls. There were few differences between coagulation markers in the 2 HIV groups. Compared with controls, the nAPCsr was lower in treated men and the TAT level was lower in untreated individuals. We observed little difference among measured levels of D-dimer, tissue factor, or F1+2 between HIV-infected individuals and controls. Antiretroviral therapy exposure was associated with a lower antithrombin level, a lower nAPCsr, and a lower ETP, while history of opportunistic infection was associated with a higher nAPCsr. Conclusions. HIV infection is associated with decreased thrombin generation, as measured by the ETP, and an increased antithrombin level. These data suggest that HIV infection may not be associated with increased propensity toward clotting, as has been suggested on the basis of isolated measures of D-dimer levels. C1 [Hsue, Priscilla Y.; Schnell, Amanda; Nitta, Elaine] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. [Martin, Jeffrey N.; Deeks, Steven G.] San Francisco Gen Hosp, Dept Med, Posit Hlth Program, San Francisco, CA 94110 USA. [Nordstrom, Sarah M.; Kohl, Louis P.; Weiss, Ethan J.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Scherzer, Rebecca; Grunfeld, Carl] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Hsue, PY (reprint author), San Francisco Gen Hosp, Div Cardiol, Room 5G1,1001 Potrero Ave, San Francisco, CA 94110 USA. EM phsue@medsfgh.ucsf.edu FU NIH [R01 HL095310]; Centers for AIDS Research at UCSF [PO AI27763]; CFAR Network of Integrated Systems [R24 AI067039]; UCSF CTSI [UL1 RR024131]; NIAID [RO1 AI087145, K24AI069994, AI 76174] FX This work was supported by grants from the NIH (R01 HL095310). The SCOPE cohort was supported by the Centers for AIDS Research at UCSF (PO AI27763), CFAR Network of Integrated Systems (R24 AI067039), the UCSF CTSI (UL1 RR024131), and the NIAID (RO1 AI087145, K24AI069994, AI 76174). NR 25 TC 11 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2012 VL 54 IS 8 BP 1196 EP 1203 DI 10.1093/cid/cis014 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 915EW UT WOS:000302007900027 PM 22438347 ER PT J AU Bogoch, II Davis, BT Hooper, DC AF Bogoch, Isaac I. Davis, Benjamin T. Hooper, David C. TI Severe Babesiosis in a Patient Treated With a Tumor Necrosis Factor alpha Antagonist SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Bogoch, Isaac I.; Davis, Benjamin T.; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bogoch, Isaac I.; Davis, Benjamin T.; Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Bogoch, II (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Cox 5,55 Fruit St, Boston, MA 02114 USA. EM isaac.bogoch@utoronto.ca NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2012 VL 54 IS 8 BP 1215 EP U2 DI 10.1093/cid/cis046 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 915EW UT WOS:000302007900031 PM 22354920 ER PT J AU Moellering, RC Ferraro, MJ AF Moellering, Robert C., Jr. Ferraro, Mary Jane TI Introduction: Solving the Clinical Problem of Vancomycin Resistance SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID STAPHYLOCOCCUS-AUREUS; ORITAVANCIN; INTEGRITY; MEMBRANE; DISRUPTS C1 [Moellering, Robert C., Jr.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Moellering, Robert C., Jr.; Ferraro, Mary Jane] Harvard Univ, Sch Med, Boston, MA USA. [Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Moellering, RC (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, 110 Francis St,Ste 6A, Boston, MA 02215 USA. EM rmoeller@bidmc.harvard.edu NR 11 TC 3 Z9 3 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2012 VL 54 SU 3 BP S201 EP S202 DI 10.1093/cid/cir1046 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 915FW UT WOS:000302010500001 PM 22431849 ER PT J AU Alonzo, MTG Lacuesta, TLV Dimaano, EM Kurosu, T Suarez, LAC Mapua, CA Akeda, Y Matias, RR Kuter, DJ Nagata, S Natividad, FF Oishi, K AF Alonzo, Maria Terrese G. Lacuesta, Talitha Lea V. Dimaano, Efren M. Kurosu, Takeshi Suarez, Lady-anne C. Mapua, Cynthia A. Akeda, Yukihiro Matias, Ronald R. Kuter, David J. Nagata, Shigekazu Natividad, Filipinas F. Oishi, Kazunori TI Platelet Apoptosis and Apoptotic Platelet Clearance by Macrophages in Secondary Dengue Virus Infections SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE ACTIVATION; DISEASE SEVERITY; BLOOD-PLATELETS; THROMBOCYTOPENIA; CELLS; PHOSPHATIDYLSERINE; PHAGOCYTOSIS; PATHOGENESIS; CASPASE; ILLNESS AB Background. The mechanisms of thrombocytopenia and platelet phagocytosis in dengue illness are not fully understood. Methods. A prospective hospital-based study was conducted to examine the relationships between platelet counts, serum thrombopoietin (TPO) levels, and platelet apoptosis and phagocytosis in 81 patients with secondary dengue virus (DV) infections and 38 healthy volunteers. The apoptosis and phagocytosis of cultured platelets after exposure to DV were also examined. Results. Platelet apoptosis, platelet phagocytosis, and serum TPO levels were increased significantly in patients during the acute and early convalescence phases compared with levels observed in patients during the convalescence phase and in healthy volunteers. A significant correlation between platelet apoptosis and platelet phagocytosis was also observed in these patients. Platelet phagocytosis was inhibited significantly by the D89E mutant, which carries a point mutation in the RGD motif of milk fat globule-epidermal growth factor 8, a phosphatidylserine-recognizing bridge molecule. DV-induced platelet apoptosis and increased phagocytosis of DV-induced apoptotic platelets was confirmed using in vitro assays. Conclusions. Our data suggest an increased phagocytosis of DV-induced apoptotic platelets by macrophages via a phosphatidylserine-recognizing pathway in secondary DV infection. Accelerated platelet clearance, however, was overcome by TPO-induced enhanced thrombopoiesis in these patients. C1 [Alonzo, Maria Terrese G.; Akeda, Yukihiro; Oishi, Kazunori] Osaka Univ, Lab Clin Res Infect Dis, Int Res Ctr Infect Dis, Microbial Dis Res Inst, Suita, Osaka 5650871, Japan. [Kurosu, Takeshi] Osaka Univ, Microbial Dis Res Inst, Dept Virol, Suita, Osaka 5650871, Japan. [Nagata, Shigekazu] Kyoto Univ, Grad Sch Med, Dept Med Chem, Kyoto 6068501, Japan. [Kuter, David J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lacuesta, Talitha Lea V.; Dimaano, Efren M.] San Lazaro Hosp, Dept Blood Borne Dis, Manila, Philippines. [Suarez, Lady-anne C.; Mapua, Cynthia A.; Matias, Ronald R.; Natividad, Filipinas F.] St Lukes Hosp, Res & Biotechnol Div, Quezon City, Philippines. RP Oishi, K (reprint author), Osaka Univ, Lab Clin Res Infect Dis, Int Res Ctr Infect Dis, Microbial Dis Res Inst, 3-1 Yamadaoka, Suita, Osaka 5650871, Japan. EM oishik@biken.osaka-u.ac.jp FU Ministry of Education, Science and Culture [22591106]; Osaka Foundation for the Promotion of Clinical Immunology; St. Lukes Medical Center [05-025] FX This work was supported by the Ministry of Education, Science and Culture (Grant-in-Aid for Scientific Research C: 22591106); the Osaka Foundation for the Promotion of Clinical Immunology; and St. Lukes Medical Center (Project 05-025). NR 38 TC 24 Z9 25 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2012 VL 205 IS 8 BP 1321 EP 1329 DI 10.1093/infdis/jis180 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 914VL UT WOS:000301980800020 PM 22383677 ER PT J AU Antony, R Emery, C Garraway, LA AF Antony, Rajee Emery, Caroline Garraway, Levi A. TI Anticipating new biochemical mechanisms of resistance to Raf inhibition in Melanoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Antony, Rajee; Garraway, Levi A.] Harvard Univ, Sch Med, DFCI, Boston, MA USA. [Emery, Caroline] Novartis Inst Biomed Res, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2953 DI 10.1158/1538-7445.AM2012-2953 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501134 ER PT J AU Antoszczyk, SJ Rabkin, SD AF Antoszczyk, Slawomir J. Rabkin, Samuel D. TI Oncolytic herpes simplex virus treatment of malignant peripheral nerve sheath tumor (MPNST) cancer stem-like cell orthotopic tumor model SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Antoszczyk, Slawomir J.; Rabkin, Samuel D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3377 DI 10.1158/1538-7445.AM2012-3377 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505345 ER PT J AU Augustyn, A Tan, C Sullivan, JP Huffman, K Girard, L Borromeo, M Johnson, J Wistuba, I Xie, Y Minna, JD AF Augustyn, Alexander Tan, Christopher Sullivan, James P. Huffman, Kenneth Girard, Luc Borromeo, Mark Johnson, Jane Wistuba, Ignacio Xie, Yang Minna, John D. TI The lineage-specific transcription factor ASCL1 defines a subtype of non-small cell lung cancer with poor prognosis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Augustyn, Alexander; Tan, Christopher; Huffman, Kenneth; Girard, Luc; Borromeo, Mark; Johnson, Jane; Xie, Yang; Minna, John D.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Sullivan, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wistuba, Ignacio] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1309 DI 10.1158/1538-7445.AM2012-1309 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502416 ER PT J AU Azarova, AM Bhatnagar, N Olsen-Drake, L Ross, K Frumm, S Liu, QS Christie, A Sanda, T Rodig, SJ Christensen, JG Kung, AL Gray, N Stegmaier, K George, RE AF Azarova, Anna M. Bhatnagar, Namrata Olsen-Drake, Lauren Ross, Kenneth Frumm, Stacey Liu, Qingsong Christie, Amanda Sanda, Takaomi Rodig, Scott J. Christensen, James G. Kung, Andrew L. Gray, Nathanael Stegmaier, Kimberley George, Rani E. TI The ATP-competitive mTOR inhibitor Torin2 enhances sensitivity of the ALK F1174L mutation to crizotinib in neuroblastoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Azarova, Anna M.; Bhatnagar, Namrata; Olsen-Drake, Lauren; Frumm, Stacey; Liu, Qingsong; Christie, Amanda; Sanda, Takaomi; Kung, Andrew L.; Gray, Nathanael; Stegmaier, Kimberley; George, Rani E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ross, Kenneth] BROAD Inst Harvard & MIT, Boston, MA USA. [Rodig, Scott J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Christensen, James G.] Pfizer Global Res & Dev, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2935 DI 10.1158/1538-7445.AM2012-2935 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602341 ER PT J AU Baena, E Shao, Z Linn, D Hamblen, M Glass, K Saumyadipta, P Fujiwara, Y Godinho, F Kim, J Al-Shhrour, F Nguyen, M Yuan, G Bronson, RT Loda, M Orkin, SH Li, Z AF Baena, Esther Shao, Zhen Linn, Douglas Hamblen, Melanie Glass, Kimberly Saumyadipta, Pyne Fujiwara, Yuko Godinho, Frank Kim, Jonghwan Al-Shhrour, Fatima Minh Nguyen Yuan, Guocheng Bronson, Roderick T. Loda, Massimo Orkin, Stuart H. Li, Zhe TI ERG and ETV1 regulate a common transcriptional network in prostate cells but in an opposite fashion SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Baena, Esther; Shao, Zhen] Childrens Hosp, Dana Farber Canc Ctr, Boston, MA 02115 USA. [Linn, Douglas; Li, Zhe] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hamblen, Melanie; Fujiwara, Yuko; Godinho, Frank; Kim, Jonghwan] Childrens Hosp, HHMI, Boston, MA 02115 USA. [Glass, Kimberly; Yuan, Guocheng; Bronson, Roderick T.; Loda, Massimo] Dana Farber Canc Ctr, Boston, MA USA. [Saumyadipta, Pyne] Dana Farber Canc Ctr, Broad Inst, Boston, MA USA. [Al-Shhrour, Fatima] Brigham & Womens Hosp, Broad Inst, Boston, MA 02115 USA. [Minh Nguyen] Childrens Hosp, Boston, MA 02115 USA. [Orkin, Stuart H.] Childrens Hosp, Dana Farber Canc Ctr, HHMI, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2965 DI 10.1158/1538-7445.AM2012-2965 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501147 ER PT J AU Bailey, ST Shin, H Liu, XS Brown, M AF Bailey, Shannon T. Shin, Hyunjin Liu, X. Shirley Brown, Myles TI The estrogen receptor regulates the transcription of p53 target genes in breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Bailey, Shannon T.; Shin, Hyunjin; Liu, X. Shirley; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-74 DI 10.1158/1538-7445.AM2012-LB-74 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501183 ER PT J AU Baker, AS Braggio, E Jacobus, S Keats, J Jung, S Larson, D Therneau, T Dispenzieri, A Van Weir, SA Ahmann, G Henderson, K Rajkumar, SV Jelinek, D Kim, S Carpten, J Fonseca, R AF Baker, Angela S. Braggio, Esteban Jacobus, Suzanna Keats, Jonathan Jung, Sungwon Larson, Dirk Therneau, Terry Dispenzieri, Angela Van Weir, Scott A. Ahmann, Gregory Henderson, Kim Rajkumar, S. Vincent Jelinek, Dianne Kim, Seungchan Carpten, John Fonseca, Rafael TI Cytogenetic and somatic characterization of myeloma tumors from a multi-ethnic cohort SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Baker, Angela S.; Keats, Jonathan; Jung, Sungwon; Kim, Seungchan; Carpten, John] Translat Genom Res Inst, Phoenix, AZ USA. [Braggio, Esteban; Van Weir, Scott A.; Ahmann, Gregory; Fonseca, Rafael] Mayo Clin, Scottsdale, AZ USA. [Jacobus, Suzanna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Larson, Dirk; Therneau, Terry; Dispenzieri, Angela; Henderson, Kim; Rajkumar, S. Vincent; Jelinek, Dianne] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5064 DI 10.1158/1538-7445.AM2012-5064 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606267 ER PT J AU Bandla, S Ruff, D Bass, A Beer, DG Zhou, ZR Li, A Chen, SM Thornton, M Luketich, JD Dulak, A Lin, L Pennathur, A Bennett, R Rothberg, J Godfrey, TE AF Bandla, Santhoshi Ruff, David Bass, Adam Beer, David G. Zhou, Zhongren Li, Alex Chen, Shiaw-Min Thornton, Michael Luketich, James D. Dulak, Austin Lin, Lin Pennathur, Arjun Bennett, Rob Rothberg, Jonathan Godfrey, Tony E. TI Targeted resequencing of genes frequently mutated in esophageal adenocarcinoma using highly multiplexed Ion Torrent AmpliSeq (TM) technology and semiconductor sequencing SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Bandla, Santhoshi; Zhou, Zhongren; Godfrey, Tony E.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Ruff, David; Li, Alex; Chen, Shiaw-Min; Thornton, Michael; Dulak, Austin; Bennett, Rob; Rothberg, Jonathan] Life Technol, Carlsbad, CA USA. [Bass, Adam] Dana Farber Canc Inst, Boston, MA 02115 USA. [Beer, David G.; Lin, Lin] Univ Michigan, Ann Arbor, MI 48109 USA. [Luketich, James D.; Pennathur, Arjun] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-410 DI 10.1158/1538-7445.AM2012-LB-410 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501270 ER PT J AU Barbone, D Cheung, P Yang, TM Jablons, DM Sugarbaker, DJ Bueno, R Fennell, DA Letai, AG Broaddus, CV AF Barbone, Dario Cheung, Priscilla Yang, Tsung-Ming Jablons, David M. Sugarbaker, David J. Bueno, Raphael Fennell, Dean A. Letai, Anthony G. Broaddus, Courtney V. TI Manipulating the Noxa/Bim axis undermines the multicellular resistance of 3D tumor spheroids SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Barbone, Dario; Cheung, Priscilla; Jablons, David M.; Broaddus, Courtney V.] UCSF, San Francisco, CA USA. [Yang, Tsung-Ming] Chang Gung Mem Hosp, Chiayi, Taiwan. [Sugarbaker, David J.; Bueno, Raphael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Fennell, Dean A.] Queens Univ, Ctr Canc Res & Cell Biol, Belfast, Antrim, North Ireland. [Letai, Anthony G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5257 DI 10.1158/1538-7445.AM2012-5257 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505181 ER PT J AU Bardia, A Dias-Santagata, D Isakoff, SJ Borger, DR Juric, D Higgins, MJ Moy, B Goss, PE Baselga, J Iafrate, AJ Ellisen, LW AF Bardia, Aditya Dias-Santagata, Dora Isakoff, Steven J. Borger, Darrell R. Juric, Dejan Higgins, Michaela J. Moy, Beverly Goss, Paul E. Baselga, Jose Iafrate, A. John Ellisen, Leif W. TI Multiplexed mutational profiling of breast tumor as an efficient clinical tool for personalized breast cancer treatment SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Bardia, Aditya; Dias-Santagata, Dora; Isakoff, Steven J.; Borger, Darrell R.; Juric, Dejan; Higgins, Michaela J.; Moy, Beverly; Goss, Paul E.; Baselga, Jose; Iafrate, A. John; Ellisen, Leif W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 962 DI 10.1158/1538-7445.AM2012-962 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701600328 ER PT J AU Basak, SK Rao, NP Oh, S Mysore, VS Srivatsan, ES Batra, RK AF Basak, Saroj Kumar Rao, Nagesh P. Oh, Scott Mysore, Veena S. Srivatsan, Eri S. Batra, Raj K. TI Tumor cell heterogeneity and chromosomal abnormality in malignant pleural effusion (MPE) samples of lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Basak, Saroj Kumar; Rao, Nagesh P.; Oh, Scott; Mysore, Veena S.; Srivatsan, Eri S.; Batra, Raj K.] Univ Calif Los Angeles, VA Greater LA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5346 DI 10.1158/1538-7445.AM2012-5346 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504122 ER PT J AU Basseres, DS D'Alo, F Yeap, BY Gonzalez, DA Yasuda, H Meyerson, M Kobayashi, S Tenen, DG Halmos, B Costa, DB AF Basseres, Daniela S. D'Alo, Francesco Yeap, Beow Y. Gonzalez, David A. Yasuda, Hiroyuki Meyerson, Matthew Kobayashi, Susumu Tenen, Daniel G. Halmos, Balazs Costa, Daniel B. TI Frequent downregulation of the transcription factor Foxa2 in lung cancer through epigenetic silencing SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Basseres, Daniela S.; D'Alo, Francesco; Gonzalez, David A.; Yasuda, Hiroyuki; Kobayashi, Susumu; Tenen, Daniel G.; Costa, Daniel B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Halmos, Balazs] Columbia Univ Coll Phys & Surg, New York Presbyterian Hosp, New York, NY 10032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4036 DI 10.1158/1538-7445.AM2012-4036 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701605325 ER PT J AU Bhasin, M Gu, XS Kung, A Libermann, TA AF Bhasin, Manoj Gu, Xuesong Kung, Andrew Libermann, Towia A. TI Identification of new drugs for treatment of renal cell cancer using genomics and the Connectivity Map Database SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Bhasin, Manoj; Gu, Xuesong; Libermann, Towia A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kung, Andrew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-351 DI 10.1158/1538-7445.AM2012-LB-351 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602385 ER PT J AU Birkbak, NJ Li, Y Wang, ZGC Silver, DP Iglehart, JD Garber, JE Szallasi, Z Richardson, AL AF Birkbak, Nicolai J. Li, Yang Wang, Zhigang C. Silver, Daniel P. Iglehart, James D. Garber, Judy E. Szallasi, Zoltan Richardson, Andrea L. TI Copy number gain and increased expression of BLM and FANCI is associated with sensitivity to genotoxic chemotherapy in triple negative breast and serous ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Birkbak, Nicolai J.; Li, Yang; Wang, Zhigang C.; Silver, Daniel P.; Iglehart, James D.; Garber, Judy E.; Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Szallasi, Zoltan] Tech Univ Denmark, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4823 DI 10.1158/1538-7445.AM2012-4823 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701600327 ER PT J AU Borad, MJ Reddy, S Uronis, H Sigal, DS Cohn, AL Schelman, WR Stephenson, J Chiorean, EG Rosen, PJ Ulrich, B Dragovich, T Del Prete, S Rarick, M Eng, C Kroll, S Ryan, D AF Borad, M. J. Reddy, S. Uronis, H. Sigal, D. S. Cohn, A. L. Schelman, W. R. Stephenson, J. Chiorean, E. G. Rosen, P. J. Ulrich, B. Dragovich, T. Del Prete, S. Rarick, M. Eng, C. Kroll, S. Ryan, D. TI Randomized phase II study of the efficacy and safety of gemcitabine + TH-302 (G+T) vs gemcitabine (G) alone in previously untreated patients with advanced pancreatic cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Borad, M. J.] Mayo Clin Arizona, Scottsdale, AZ USA. [Reddy, S.] Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA. [Uronis, H.] Duke Univ, Med Ctr, Durham, NC USA. [Sigal, D. S.] Scripps Clin Med Grp, La Jolla, CA USA. [Cohn, A. L.] Rocky Mt Canc Ctr, Denver, CO USA. [Schelman, W. R.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Stephenson, J.] Inst Translat Oncol Res, Greenville, SC USA. [Chiorean, E. G.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Rosen, P. J.] Providence St Joseph Med Ctr, Burbank, CA USA. [Ulrich, B.] Texas Oncol, Wichita Falls, TX USA. [Dragovich, T.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Del Prete, S.] Hematol Oncol PC, Stamford, CT USA. [Rarick, M.] Kaiser Permanente Northwest Reg Oncol Hematol, Portland, OR USA. [Eng, C.; Kroll, S.] Threshold Pharmaceut, San Francisco, CA USA. [Ryan, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-121 DI 10.1158/1538-7445.AM2012-LB-121 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701601396 ER PT J AU Buchwalter, G Brown, M AF Buchwalter, Gilles Brown, Myles TI PDEF regulation and role as a survival factor in ER positive breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Buchwalter, Gilles; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2256 DI 10.1158/1538-7445.AM2012-2256 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502089 ER PT J AU Capelletti, M Lipson, D Otto, G Yelensky, R Ercan, D Kim, JK Sasaki, H Kim, HR Park, SI Ross, J Stephens, PJ Cronin, MT Janne, PA AF Capelletti, Marzia Lipson, Doron Otto, Geoff Yelensky, Roman Ercan, Dalia Kim, Jhingook Kim Sasaki, Hidefumi Kim, Hyeong Ryul Park, Seung-Il Ross, Jeffrey Stephens, Philip J. Cronin, Maureen T. Janne, Pasi A. TI Identification of recurrent oncogenic KIF5B-RET rearrangements in non -small cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Capelletti, Marzia; Ercan, Dalia; Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lipson, Doron; Otto, Geoff; Yelensky, Roman; Stephens, Philip J.; Cronin, Maureen T.] Fdn Med, Boston, MA USA. [Kim, Jhingook Kim] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Sasaki, Hidefumi] Nagoya City Univ, Grad Sch Med Sci, Nagoya, Aichi, Japan. [Kim, Hyeong Ryul; Park, Seung-Il] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. [Ross, Jeffrey] Albany Med Coll, Albany, NY 12208 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-88 DI 10.1158/1538-7445.AM2012-LB-88 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701605245 ER PT J AU Chang, I Liu, J Majid, S Saini, S Zaman, MS Yamamura, S Shahryari, V Chiyomaru, T Deng, GR Dahiya, R Tanaka, Y AF Chang, Inik Liu, Jan Majid, Shahana Saini, Sharanjot Zaman, Mohd S. Yamamura, Soichiro Shahryari, Vary Chiyomaru, Takeshi Deng, Guoren Dahiya, Rajvir Tanaka, Yuichiro TI Protective effect of catechol-O-methyltransferase-mediated 4-hydroxyestradiol metabolism in human renal cell cancers SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Chang, Inik; Liu, Jan; Majid, Shahana; Saini, Sharanjot; Zaman, Mohd S.; Yamamura, Soichiro; Shahryari, Vary; Chiyomaru, Takeshi; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro] San Francisco VA Med Ctr, San Francisco, CA USA. [Chang, Inik; Liu, Jan; Majid, Shahana; Saini, Sharanjot; Zaman, Mohd S.; Yamamura, Soichiro; Shahryari, Vary; Chiyomaru, Takeshi; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro] UCSF, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1860 DI 10.1158/1538-7445.AM2012-1860 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701500102 ER PT J AU Chen, S Johnson, N Auger, KR Xiao, YH Ying, HG Marszalek, J Middleton, R Andersen, JN McGrath, JP Chin, L AF Chen, Shujuan Johnson, Natalie Auger, Kurt R. Xiao, Yonghong Ying, Haogiang Marszalek, Joseph Middleton, Richard Andersen, Jannik N. McGrath, John P. Chin, Lynda TI Characterization of a selective focal adhesion kinase (FAK) inhibitor in a panel of glioblastoma cell lines identify rational drug-drug combination strategies SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Chen, Shujuan; Johnson, Natalie; Xiao, Yonghong; Ying, Haogiang; Middleton, Richard; McGrath, John P.] Harvard Univ, Sch Med, DFCI, Boston, MA USA. [Auger, Kurt R.] GlaxoSmithKline, Off 1E 4406, UP1450, Collegeville, PA USA. [Marszalek, Joseph; Andersen, Jannik N.; Chin, Lynda] MD Anderson, Houston, TX USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3714 DI 10.1158/1538-7445.AM2012-3714 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701603198 ER PT J AU Chiyomaru, T Zaman, MS Majid, S Deng, GR Yamamura, S Shahryari, V Saini, S Hirata, H Ueno, K Chang, I Tanaka, Y Enikida, H Nakagawa, M Dahiya, R AF Chiyomaru, Takeshi Zaman, Mohd Saif Majid, Shahana Deng, Guoren Yamamura, Soichiro Shahryari, Varahram Saini, Sharanjot Hirata, Hiroshi Ueno, Koji Chang, Inik Tanaka, Yuichiro Enikida, Hideki Nakagawa, Masayuki Dahiya, Rajvir TI Genistein suppresses prostate cancer growth through inhibition of oncogenic miR-151 SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Chiyomaru, Takeshi; Zaman, Mohd Saif; Majid, Shahana; Deng, Guoren; Yamamura, Soichiro; Shahryari, Varahram; Saini, Sharanjot; Hirata, Hiroshi; Ueno, Koji; Chang, Inik; Tanaka, Yuichiro; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. [Chiyomaru, Takeshi; Zaman, Mohd Saif; Majid, Shahana; Deng, Guoren; Yamamura, Soichiro; Shahryari, Varahram; Saini, Sharanjot; Hirata, Hiroshi; Ueno, Koji; Chang, Inik; Tanaka, Yuichiro; Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Enikida, Hideki; Nakagawa, Masayuki] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Urol, Kagoshima 890, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2299 DI 10.1158/1538-7445.AM2012-2299 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502312 ER PT J AU Cibulskis, K Sivachenko, A Hammerman, P Imaz, I Pugh, T Sougnezl, C Winckler, W Gabriel, S Getz, G AF Cibulskis, Kristian Sivachenko, Andrey Hammerman, Peter Imaz, Ivan Pugh, Trevor Sougnezl, Carrie Winckler, Wendy Gabriel, Stacey Getz, Gaddy TI Rapid and efficient large-scale somatic mutation validation approaches for cancer genome sequencing SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Cibulskis, Kristian; Sivachenko, Andrey; Pugh, Trevor; Sougnezl, Carrie; Winckler, Wendy; Gabriel, Stacey; Getz, Gaddy] Broad Inst, Cambridge, MA USA. [Hammerman, Peter] Dana Farber Canc Inst, Boston, MA 02115 USA. [Imaz, Ivan] Inst Nacl Med Genom, Mexico City, DF, Mexico. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3960 DI 10.1158/1538-7445.AM2012-3960 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701605061 ER PT J AU Cleary, JM Yee, LKC Azad, N Carducci, M Cosgrove, D Limaye, S Gandhi, L Pedersen, M Ansell, P Ames, W Sharma, S Hsu, YH Munasinghe, W Reilly, E Holen, KD Humerickhouse, R AF Cleary, James M. Yee, Lorrin Kwock-Chong Azad, Nilofer Carducci, Michael Cosgrove, David Limaye, Sewanti Gandhi, Leena Pedersen, Michelle Ansell, Peter Ames, William Sharma, Shringi Hsu, Ya-Hui Munasinghe, Wijith Reilly, Edward Holen, Kyle D. Humerickhouse, Rod TI A phase 1 study of ABT-806, a humanized recombinant anti-EGFR monoclonal antibody, in patients with advanced solid tumors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Cleary, James M.; Limaye, Sewanti; Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yee, Lorrin Kwock-Chong] Northwest Med Specialists, Tacoma, WA USA. [Azad, Nilofer; Carducci, Michael; Cosgrove, David] Johns Hopkins Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Pedersen, Michelle; Ansell, Peter; Ames, William; Sharma, Shringi; Hsu, Ya-Hui; Munasinghe, Wijith; Reilly, Edward; Holen, Kyle D.; Humerickhouse, Rod] Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2506 DI 10.1158/1538-7445.AM2012-2506 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701500253 ER PT J AU Cohen, NA Stewart, ML Gavathiotis, E Tepper, JL Opferman, JT Walensky, LD AF Cohen, Nicole A. Stewart, Michelle L. Gavathiotis, Evripidis Tepper, Jared L. Opferman, Joseph T. Walensky, Loren D. TI Selective small molecule inhibition of anti-apoptotic MCL-1 SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Cohen, Nicole A.; Stewart, Michelle L.; Tepper, Jared L.; Walensky, Loren D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gavathiotis, Evripidis] Albert Einstein Coll Med, New York, NY USA. [Opferman, Joseph T.] St Jude Childrens Res Hosp, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4851 DI 10.1158/1538-7445.AM2012-4851 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501100 ER PT J AU Corcoran, RB Cheng, KA Wong, KK Engelman, JA AF Corcoran, Ryan B. Cheng, Katherine A. Wong, Kwok-Kin Engelman, Jeffrey A. TI Marked in vivo efficacy of combined BCLXL and MEK inhibition in KRAS mutant cancers revealed by a pooled shRNA-drug screen for genes that are "synthetically lethal" with MEK inhibitors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Corcoran, Ryan B.; Engelman, Jeffrey A.] MGH, Ctr Canc, Boston, MA USA. [Cheng, Katherine A.; Wong, Kwok-Kin] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 875 DI 10.1158/1538-7445.AM2012-875 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701604011 ER PT J AU Moreno, TD Croci, DO Cerliani, JP Dylon, SLD Mascanfroni, I Osinaga, E Shipp, MA Rabinovich, GA Salatino, M AF D'Alotto Moreno, Tomas Croci, Diego O. Cerliani, Juan P. Dergan Dylon, Sebastian L. Mascanfroni, Ivan Osinaga, Eduardo Shipp, Margaret A. Rabinovich, Gabriel A. Salatino, Mariana TI Disruption of Galectin1-glycan interaction impairs tumor growth and metastasis in breast cancer by disarming the immunosuppressive capacity of regulatory T cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [D'Alotto Moreno, Tomas; Croci, Diego O.; Cerliani, Juan P.; Dergan Dylon, Sebastian L.; Mascanfroni, Ivan; Rabinovich, Gabriel A.; Salatino, Mariana] Inst Biol & Expt Med, Buenos Aires, DF, Argentina. [Osinaga, Eduardo] Univ Republica, Sch Med, Montevideo, Uruguay. [Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3547 DI 10.1158/1538-7445.AM2011-3547 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701500455 ER PT J AU D'Andrea, AD AF D'Andrea, Alan D. TI Targeting the Fanconi anemia/BRCA pathway in cancer therapy SO CANCER RESEARCH LA English DT Meeting Abstract C1 [D'Andrea, Alan D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA SY11-01 DI 10.1158/1538-7445.AM2012-SY11-01 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501044 ER PT J AU Daubriac, J Boucher, Y AF Daubriac, Julien Boucher, Yves TI Cross-talk between carcinoma associated fibroblasts and invasive breast cancer cells: Role of RhoA / ROCK signaling SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Daubriac, Julien; Boucher, Yves] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1529 DI 10.1158/1538-7445.AM2012-1529 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502207 ER PT J AU Deng, XY Hoff, J Novak, M Kaetzel, D Hemler, ME Yang, XWH AF Deng, Xinyu Hoff, John Novak, Marian Kaetzel, David Hemler, Martin E. Yang, Xiuwei H. TI Tetraspanin CD151 drives mammary tumor onset and metastasis by coordinating integrin-dependent cell adhesion, motility, survival and signaling SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Deng, Xinyu; Hoff, John; Novak, Marian; Kaetzel, David; Yang, Xiuwei H.] Univ Kentucky, Lexington, KY USA. [Hemler, Martin E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2704 DI 10.1158/1538-7445.AM2012-2704 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601345 ER PT J AU Duan, ZF Choy, E Harmon, D Mankin, H Hornicek, F AF Duan, Zhenfeng Choy, Edwin Harmon, David Mankin, Henry Hornicek, Francis TI CDK11 (PITSLRE) kinase expression is critical for human cancer cell growth and proliferation SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Duan, Zhenfeng; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 859 DI 10.1158/1538-7445.AM2012-859 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701603410 ER PT J AU Eichhorn, PJ Rodon, L Gonzalez-Junca, A Baselga, J Seoane, J AF Eichhorn, Pieter J. Rodon, Laura Gonzalez-Junca, Alba Baselga, Jose Seoane, Joan TI USP15 stabilizes the TGF-beta receptor I and promotes oncogenesis through the activation of the TGF-beta signal in glioblastoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Eichhorn, Pieter J.; Baselga, Jose] Massachusetts Gen Hosp, Charlestown, MA USA. [Rodon, Laura; Gonzalez-Junca, Alba; Seoane, Joan] Vall dHebron Inst Oncol, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-31 DI 10.1158/1538-7445.AM2012-LB-31 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501214 ER PT J AU Engler, D Gupta, S Growdan, W Drapkin, R Nitta, M Sergent, P Allred, S Gross, J Deavers, M Kuo, WL Karlan, B Rueda, B Orsulic, S Gershenson, D Birrer, M Gray, J Mohapatra, G AF Engler, David Gupta, Sumeet Growdan, Whitfield Drapkin, Ronny Nitta, Mai Sergent, Petra Allred, Serena Gross, Jenny Deavers, Michael Kuo, Wen-Lin Karlan, Beth Rueda, Bo Orsulic, Sandra Gershenson, David Birrer, Michael Gray, Joe Mohapatra, Gayatry TI Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Engler, David; Allred, Serena] Brigham Young Univ, Provo, UT 84602 USA. [Gupta, Sumeet] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Growdan, Whitfield; Nitta, Mai; Sergent, Petra; Rueda, Bo; Birrer, Michael; Mohapatra, Gayatry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gross, Jenny; Karlan, Beth; Orsulic, Sandra] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Deavers, Michael; Gershenson, David] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kuo, Wen-Lin; Gray, Joe] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5093 DI 10.1158/1538-7445.AM2012-5093 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606297 ER PT J AU Ercan, D Xie, T Capelletti, M Gray, NS Janne, PA AF Ercan, Dalia Xie, Ting Capelletti, Marzia Gray, Nathanael S. Janne, Pasi A. TI Novel EGFR mutations that cause drug resistance to irreversible pyrimidine but not quinazoline based EGFR inhibitors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ercan, Dalia; Xie, Ting; Capelletti, Marzia; Gray, Nathanael S.; Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4832 DI 10.1158/1538-7445.AM2012-4832 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602323 ER PT J AU Farley, JH Brady, WE Birrer, MJ Lankes, H Coleman, R Morgan, M Mannel, R Yamada, D Mutch, D Rodgers, WH Gershenson, DM AF Farley, John H. Brady, William E. Birrer, Michael J. Lankes, Heather Coleman, Robert Morgan, Mark Mannel, Robert Yamada, Diane Mutch, David Rodgers, William H. Gershenson, David M. TI A phase II trial of selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Farley, John H.] St Josephs Hosp, Phoenix, AZ USA. [Brady, William E.; Lankes, Heather] Roswell Pk Canc Inst, Stat & Data Ctr, Gynecol Oncol Grp, Buffalo, NY 14263 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Coleman, Robert; Gershenson, David M.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Morgan, Mark] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Mannel, Robert] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Yamada, Diane] Univ Chicago, Gynecol Oncol Sect, Chicago, IL 60637 USA. [Mutch, David] Washington Univ, Sch Med, Dept OB GYN, St Louis, MO USA. [Rodgers, William H.] Lenox Hill Hosp, Dept Pathol, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA CT-05 DI 10.1158/1538-7445.AM2012-CT-05 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601407 ER PT J AU Fulciniti, M Munshi, M Xu, L Calimeri, T Anderson, KC Treon, S Munshi, NC AF Fulciniti, Mariateresa Munshi, Mansa Xu, Lian Calimeri, Teresa Anderson, Kenneth C. Treon, Steven Munshi, Nikhil C. TI Targeting Sp1 transactivation in Waldenstrom's macroglobulinemia: A novel therapeutic option SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Fulciniti, Mariateresa; Munshi, Mansa; Xu, Lian; Calimeri, Teresa; Anderson, Kenneth C.; Treon, Steven; Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 288 DI 10.1158/1538-7445.AM2012-288 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502351 ER PT J AU Garcia, EP Shivdasani, P Sharaf, N Crosby, L Byrne, MN Wade, JE Joshi, R Ducar, M Palescandolo, E Van Hummelen, P Lindeman, NI Kuo, FC Longtine, JA MacConaill, LE AF Garcia, Elizabeth P. Shivdasani, Priyanka Sharaf, Nematullah Crosby, Lauren Byrne, Mark N. Wade, Jacqueline E. Joshi, Ruchi Ducar, Matthew Palescandolo, Emanuele Van Hummelen, Paul Lindeman, Neal I. Kuo, Frank C. Longtine, Janina A. MacConaill, Laura E. TI Application of a high throughput cancer mutation profiling platform to clinical research SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Garcia, Elizabeth P.; Shivdasani, Priyanka; Sharaf, Nematullah; Crosby, Lauren; Byrne, Mark N.; Wade, Jacqueline E.; Joshi, Ruchi; Lindeman, Neal I.; Kuo, Frank C.; Longtine, Janina A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ducar, Matthew; Palescandolo, Emanuele; Van Hummelen, Paul; MacConaill, Laura E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5058 DI 10.1158/1538-7445.AM2012-5058 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606261 ER PT J AU Garcia-Garcia, C Ibrahim, YH Serra, V Calvo, MT Guzman, M Grueso, J Aura, C Perez, J Jesen, K Liu, Y Rommel, C Tabernero, J Baselga, J Scaltriti, M AF Garcia-Garcia, Celina Ibrahim, Yasir H. Serra, Violeta Teresa Calvo, Maria Guzman, Marta Grueso, Judit Aura, Claudia Perez, Jose Jesen, Katti Liu, Yi Rommel, Christian Tabernero, Josep Baselga, Jose Scaltriti, Maurizio TI Antitumor activity of lapatinib in combination with the dual mTORC1/2 inhibitor INK-128 in breast tumors resistant to anti-HER2 therapy SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Garcia-Garcia, Celina; Ibrahim, Yasir H.; Serra, Violeta; Teresa Calvo, Maria; Guzman, Marta; Grueso, Judit; Aura, Claudia; Perez, Jose; Tabernero, Josep] VHIO, Barcelona, Spain. [Jesen, Katti; Liu, Yi; Rommel, Christian] Intellikine, La Jolla, CA USA. [Baselga, Jose; Scaltriti, Maurizio] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1811 DI 10.1158/1538-7445.AM2012-1811 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701603454 ER PT J AU Gavathiotis, E LaBelle, JL Reyna, D Bellairs, J Walensky, LD AF Gavathiotis, Evripidis LaBelle, James L. Reyna, Denis Bellairs, Joseph Walensky, Loren D. TI Direct activation of pro-apoptotic BAX as a novel strategy for cancer therapy SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Gavathiotis, Evripidis; Reyna, Denis] Albert Einstein Coll Med, New York, NY USA. [LaBelle, James L.; Bellairs, Joseph; Walensky, Loren D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 972 DI 10.1158/1538-7445.AM2012-972 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602318 ER PT J AU Ghosh, R Narasanna, A Chakrabarty, A Engelman, JA Arteaga, CL AF Ghosh, Ritwik Narasanna, Archana Chakrabarty, Anindita Engelman, Jeffrey A. Arteaga, Carlos L. TI HER2 gene-amplified human breast cancer cells harboring a gatekeeper T768M mutation in HER2 overexpress EGFR ligands and are sensitive to dual therapeutic blockade of EGFR and HER2 SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ghosh, Ritwik; Narasanna, Archana; Chakrabarty, Anindita; Arteaga, Carlos L.] Vanderbilt Univ, Nashville, TN 37235 USA. [Engelman, Jeffrey A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3 DI 10.1158/1538-7445.AM2012-3 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701604385 ER PT J AU Gonzalez-Angulo, AM Krop, I Piha-Paul, S Li, YS Culotta, KS Moulder-Thompson, S Tsimberidou, A Velez-Bravo, VM Madden, TL Norberg, LM Doyle, A Winder, EP Mills, GB Meric-Bernstam, F Kurzrock, R AF Gonzalez-Angulo, Ana M. Krop, Ian Piha-Paul, Sarina Li, Yisheng Culotta, Kirk S. Moulder-Thompson, Stacy Tsimberidou, Apostolia Velez-Bravo, Vivianne M. Madden, Timothy L. Norberg, Lisa M. Doyle, Austin Winder, Eric P. Mills, Gordon B. Meric-Bernstam, Funda Kurzrock, Razelle TI Phase lb dose escalation and biomarker study of MK2206 in combination with standard doses of weekly paclitaxel in patients with locally advanced or metastatic solid tumors with expansion in advanced breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Gonzalez-Angulo, Ana M.; Piha-Paul, Sarina; Li, Yisheng; Culotta, Kirk S.; Moulder-Thompson, Stacy; Tsimberidou, Apostolia; Velez-Bravo, Vivianne M.; Madden, Timothy L.; Norberg, Lisa M.; Mills, Gordon B.; Meric-Bernstam, Funda; Kurzrock, Razelle] UT MD Anderson Canc Ctr, Houston, TX USA. [Krop, Ian; Winder, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Doyle, Austin] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-231 DI 10.1158/1538-7445.AM2012-LB-231 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601425 ER PT J AU Greulich, H Kaplan, B Mertins, P Chen, TH Tanaka, K Yun, CH Imielinski, M Banerji, S Lawrence, MS Walker, S Winckler, W Getz, G Frank, D Eck, M Jaffe, JD Carr, SA Wong, KK Meyerson, M AF Greulich, Heidi Kaplan, Bethany Mertins, Philipp Chen, Tzu-Hsiu Tanaka, Kumiko Yun, Cai-Hong Imielinski, Marcin Banerji, Shanatanu Lawrence, Michael S. Walker, Sarah Winckler, Wendy Getz, Gad Frank, David Eck, Michael Jaffe, Jacob D. Carr, Steven A. Wong, Kwok-Kin Meyerson, Matthew TI Oncogenic extracellular domain mutations of ERBB2 in cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Greulich, Heidi; Kaplan, Bethany; Tanaka, Kumiko; Banerji, Shanatanu; Walker, Sarah; Frank, David; Eck, Michael; Wong, Kwok-Kin; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mertins, Philipp; Chen, Tzu-Hsiu; Imielinski, Marcin; Lawrence, Michael S.; Winckler, Wendy; Getz, Gad; Jaffe, Jacob D.; Carr, Steven A.] Broad Inst, Cambridge, MA USA. [Yun, Cai-Hong] Peking Univ, Hlth Sci Ctr, Beijing 100871, Peoples R China. OI wong, kwok kin/0000-0001-6323-235X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1 DI 10.1158/1538-7445.AM2012-1 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701604383 ER PT J AU Groeneweg, JW Tambouret, RH Borger, DR Foster, R Rueda, BR Growdon, WB AF Groeneweg, Jolijn W. Tambouret, Rosemary H. Borger, Darrell R. Foster, Rosemary Rueda, Bo R. Growdon, Whitfield B. TI Epidermal growth factor signaling alterations in uterine papillary serous carcinoma (UPSC) associate with survival SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Groeneweg, Jolijn W.; Tambouret, Rosemary H.; Borger, Darrell R.; Foster, Rosemary; Rueda, Bo R.; Growdon, Whitfield B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Groeneweg, Jolijn W.; Tambouret, Rosemary H.; Borger, Darrell R.; Foster, Rosemary; Rueda, Bo R.; Growdon, Whitfield B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4556 DI 10.1158/1538-7445.AM2012-4556 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601202 ER PT J AU Haeno, H Gonen, M Davis, MB Herman, JM Lacobuzio-Donahue, CA Michor, F AF Haeno, Hiroshi Gonen, Mithat Davis, Meghan B. Herman, Joseph M. Lacobuzio-Donahue, Christine A. Michor, Franziska TI Computational modeling of pancreatic cancer reveals growth and dissemination kinetics and suggests optimum treatment strategies SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Haeno, Hiroshi; Michor, Franziska] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gonen, Mithat] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Davis, Meghan B.; Herman, Joseph M.; Lacobuzio-Donahue, Christine A.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3961 DI 10.1158/1538-7445.AM2012-3961 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701605062 ER PT J AU Harris, M Shin, DM Choi, S Low, B Miller, E Rybinski, B Bronson, R Yun, K AF Harris, Molly Shin, Dong-mi Choi, Seungbum Low, Benjamin Miller, Emily Rybinski, Brad Bronson, Roderick Yun, Kyuson TI Cancer stem cell heterogeneity and cell-of-origin in medulloblastomas SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Harris, Molly] Univ Maine, Orono, ME USA. [Shin, Dong-mi] NIAID, NIH, Bethesda, MD 20892 USA. [Choi, Seungbum; Low, Benjamin; Miller, Emily; Rybinski, Brad; Yun, Kyuson] Jackson Lab, Ctr Canc, Bar Harbor, ME 04609 USA. [Bronson, Roderick] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3300 DI 10.1158/1538-7445.AM2012-3300 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504443 ER PT J AU Hatton, C Niu, LL Davis, M Mondal, C Luongo, L Go, C Jones, RT Roden, C Palescandolo, E Van Hummelen, P Garraway, LA Meyerson, M Hahn, W MacConaill, LE AF Hatton, Charles Niu, Lili Davis, Matthew Mondal, Chandrani Luongo, Lauren Go, Christina Jones, Robert T. Roden, Christine Palescandolo, Emanuele Van Hummelen, Paul Garraway, Levi A. Meyerson, Matthew Hahn, William MacConaill, Laura E. TI An algorithm to detect somatic mutations in cancer specimens using mass spectrometric genotyping SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Hatton, Charles; Niu, Lili; Davis, Matthew; Mondal, Chandrani; Luongo, Lauren; Go, Christina; Jones, Robert T.; Roden, Christine; Palescandolo, Emanuele; Van Hummelen, Paul; Garraway, Levi A.; Meyerson, Matthew; Hahn, William; MacConaill, Laura E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3965 DI 10.1158/1538-7445.AM2012-3965 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701605066 ER PT J AU He, HH Meyer, CA Liu, SX Brown, M AF He, Housheng H. Meyer, Clifford A. Liu, Shirley X. Brown, Myles TI Factor dependent chromatin structure and nucleosome dynamics SO CANCER RESEARCH LA English DT Meeting Abstract C1 [He, Housheng H.; Meyer, Clifford A.; Liu, Shirley X.; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2960 DI 10.1158/1538-7445.AM2012-2960 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501141 ER PT J AU Helman, E Lawrence, M Stewart, C Getz, G Meyerson, M AF Helman, Elena Lawrence, Mike Stewart, Chip Getz, Gad Meyerson, Matthew TI Identification of somatic retrotransposon insertions across cancer types using RetroSeq SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Helman, Elena] Harvard MIT Hlth Sci Technol, Cambridge, MA USA. [Lawrence, Mike; Stewart, Chip; Getz, Gad] Broad Inst, Cambridge, MA USA. [Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5060 DI 10.1158/1538-7445.AM2012-5060 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606263 ER PT J AU Hettmer, S Lindsay, MC Langenau, DM Wagers, AJ AF Hettmer, Simone Lindsay, Melissa C. Langenau, David M. Wagers, Amy J. TI Sarcoma-relevant genetic events identified in a chimeric mouse model of sarcoma in skeletal muscle SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Hettmer, Simone] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lindsay, Melissa C.; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Langenau, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1361 DI 10.1158/1538-7445.AM2012-1361 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504410 ER PT J AU Hodis, E Watson, I Theurillats, JP Zou, LH Place, C Nickerson, E Auclair, D Cibulskis, K Sivachenko, A Kryukov, G Stransky, N Ramos, AH Voet, D Lawrence, MS Stojanov, P Saksena, G McKenna, A Carter, SL Pugh, T Noble, M Lin, P Lichtenstein, L Ambrogio, L Fennell, T Chong, K Winckler, W Ardlie, K Landers, ES Golub, T Meyerson, M Gabrie, SB Getz, G Wagner, S Schadendorf, D Hoon, DSB Chin, L Garraway, LA AF Hodis, Eran Watson, Ian Theurillats, Jean-Philippe Zou, Lihua Place, Chelsea Nickerson, Elizabeth Auclair, Daniel Cibulskis, Kristian Sivachenko, Andrey Kryukov, Gregory Stransky, Nicolas Ramos, Alex H. Voet, Douglas Lawrence, Michael S. Stojanov, Petar Saksena, Gordon McKenna, Aaron Carter, Scott L. Pugh, Trevor Noble, Michael Lin, Pei Lichtenstein, Lee Ambrogio, Lauren Fennell, Timothy Chong, Kelly Winckler, Wendy Ardlie, Kristin Landers, Eric S. Golub, Todd Meyerson, Matthew Gabrie, Stacey B. Getz, Gad Wagner, Stefan Schadendorf, Dirk Hoon, Dave S. B. Chin, Lynda Garraway, Levi A. TI A glimpse into the somatic mutation landscape of melanoma through exome sequencing of 121 tumor-normal pairs SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Hodis, Eran; Theurillats, Jean-Philippe; Zou, Lihua; Nickerson, Elizabeth; Auclair, Daniel; Cibulskis, Kristian; Sivachenko, Andrey; Kryukov, Gregory; Stransky, Nicolas; Ramos, Alex H.; Voet, Douglas; Lawrence, Michael S.; Stojanov, Petar; Saksena, Gordon; McKenna, Aaron; Carter, Scott L.; Pugh, Trevor; Noble, Michael; Lin, Pei; Lichtenstein, Lee; Ambrogio, Lauren; Fennell, Timothy; Winckler, Wendy; Ardlie, Kristin; Landers, Eric S.; Golub, Todd; Meyerson, Matthew; Gabrie, Stacey B.; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA USA. [Watson, Ian; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Place, Chelsea; Garraway, Levi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chong, Kelly; Hoon, Dave S. B.] John Wayne Canc Ctr, Santa Monica, CA USA. [Wagner, Stefan] Med Univ Vienna, Vienna, Austria. [Schadendorf, Dirk] Univ Hosp Essen, Essen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5056 DI 10.1158/1538-7445.AM2012-5056 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606258 ER PT J AU Pham, H Chen, M Takahashi, H Reber, HA Hines, J Eibl, G AF Hung Pham Chen, Monica Takahashi, Hiroki Reber, Howard A. Hines, Joe Eibl, Guido TI Vitamin 03 induces 15-Hydroxyprostaglandin Dehydrogenase to suppress pancreatic cancer cell proliferation SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Hung Pham] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Chen, Monica; Takahashi, Hiroki; Reber, Howard A.; Hines, Joe; Eibl, Guido] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 62 DI 10.1158/1538-7445.AM2012-62 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701605243 ER PT J AU Ibrahim, YH Garcia-Garcia, C Serra, V Scaltriti, M Juric, D Anton, P Guzman, M Cozar, P Aura, C Jimenez, J Rubio, I Perez, J Balmana, J Baselga, J AF Ibrahim, Yasir H. Garcia-Garcia, Celina Serra, Violeta Scaltriti, Maurizio Juric, Dejan Anton, Pilar Guzman, Marta Cozar, Patricia Aura, Claudia Jimenez, Jose Rubio, Isabel Perez, Jose Balmana, Judith Baselga, Jose TI PI3K inhibition sensitizes to PARP inhibitors in patient-derived xenograft models of triple negative breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ibrahim, Yasir H.; Garcia-Garcia, Celina; Serra, Violeta; Anton, Pilar; Guzman, Marta; Cozar, Patricia; Aura, Claudia; Jimenez, Jose; Rubio, Isabel; Perez, Jose; Balmana, Judith] VHIO, Barcelona, Spain. [Scaltriti, Maurizio; Juric, Dejan; Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3746 DI 10.1158/1538-7445.AM2012-3746 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701603371 ER PT J AU Jain, RK AF Jain, Rakesh K. TI Normalizing the tumor microenvironment to enhance therapeutic outcome SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA PL02-01 DI 10.1158/1538-7445.AM2012-PL02-01 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501087 ER PT J AU Janiszewska, M Suva, ML Riggi, N Stamenkovic, I AF Janiszewska, Michalina Suva, Mario-Luca Riggi, Nicolo Stamenkovic, Ivan TI Imp2 controls oxidative phosphorylation in glioblastoma cancer stem cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Janiszewska, Michalina; Stamenkovic, Ivan] Univ Lausanne, Lausanne, Switzerland. [Suva, Mario-Luca; Riggi, Nicolo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1137 DI 10.1158/1538-7445.AM2012-1137 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606045 ER PT J AU Jin, HY Hoff, JT Deng, XY Drapkin, RI Yang, XWH AF Jin, Hongyan Hoff, John T. Deng, Xinyu Drapkin, Ronny I. Yang, Xiuwei H. TI A role of integrin-associated CD151 in human ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Jin, Hongyan; Hoff, John T.; Deng, Xinyu; Yang, Xiuwei H.] Univ Kentucky, Lexington, KY USA. [Drapkin, Ronny I.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4613 DI 10.1158/1538-7445.AM2012-4613 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601384 ER PT J AU Juric, D Dienstmann, R Messersmith, W Cervantes, A Blumenschein, G Baselga, J Tabernero, J Jimeno, A Calles, A Roda, D Xin, Y Kapp, AV Chandler, GS Pirzkall, A Hidalgo, M AF Juric, Dejan Dienstmann, Rodrigo Messersmith, Wells Cervantes, Andres Blumenschein, George Baselga, Jose Tabernero, Josep Jimeno, Antonio Calles, Antonio Roda, Desamparados Xin, Yan Kapp, Amy V. Chandler, G. Scott Pirzkall, Andrea Hidalgo, Manuel TI A Phase 1 study of MEHD7945A (MEHD), a first-in-class EGFR/HER3 dual action antibody, in patients (pts) with locally advanced or metastatic epithelial tumors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Juric, Dejan; Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Dienstmann, Rodrigo; Tabernero, Josep] Vall dHebron Inst Oncol, Dept Med Oncol, Barcelona, Spain. [Messersmith, Wells; Jimeno, Antonio] Univ Colorado, Ctr Canc, Div Med Oncol, Denver, CO 80262 USA. [Cervantes, Andres; Roda, Desamparados] Univ Valencia, Hematol & Med Oncol, INCLIVA Hlth Res Inst, Valencia, Spain. [Blumenschein, George] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Calles, Antonio; Hidalgo, Manuel] Spanish Natl Canc Res Ctr, Gastrointestinal Canc Clin Res Unit, Madrid, Spain. [Xin, Yan; Kapp, Amy V.; Chandler, G. Scott; Pirzkall, Andrea] Genentech Inc, San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA CT-08 DI 10.1158/1538-7445.AM2012-CT-08 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701601409 ER PT J AU Juric, D Rodon, J Gonzalez-Angulo, AM Burris, HA Bendell, J Berlin, JD Middleton, MR Bootle, D Boehm, M Schmitt, A Rouyrre, N Quadt, C Baseiga, J AF Juric, Dejan Rodon, Jordi Gonzalez-Angulo, Ana M. Burris, Howard A. Bendell, Johanna Berlin, Jordan D. Middleton, Mark R. Bootle, Douglas Boehm, Markus Schmitt, Antonin Rouyrre, Nicolas Quadt, Cornelia Baseiga, Jose TI BYL719, a next generation PI3K alpha specific inhibitor: Preliminary safety, PK, and efficacy results from the first-in-human study SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Juric, Dejan; Baseiga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Rodon, Jordi] Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain. [Gonzalez-Angulo, Ana M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Burris, Howard A.; Bendell, Johanna] Sarah Cannon Res Inst, Nashville, TN USA. [Berlin, Jordan D.] Vanderbilt Canc Ctr, Nashville, TN USA. [Middleton, Mark R.] Churchill Hosp, Dept Med Oncol, Oxford OX3 7LJ, England. [Bootle, Douglas; Boehm, Markus; Schmitt, Antonin; Rouyrre, Nicolas; Quadt, Cornelia] Novartis Pharma AG, Basel, Switzerland. NR 0 TC 4 Z9 4 U1 5 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA CT-01 DI 10.1158/1538-7445.AM2012-CT-01 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701601402 ER PT J AU Katz, SG Fisher, JK Bronson, RT Ligon, KL Walensky, LD AF Katz, Samuel G. Fisher, Jill K. Bronson, Roderick T. Ligon, Keith L. Walensky, Loren D. TI Neural progenitor cells deficient in BAX and BAK manifest progressive hyperplasia and tumorigenesis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Katz, Samuel G.; Fisher, Jill K.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Katz, Samuel G.; Fisher, Jill K.; Walensky, Loren D.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. [Bronson, Roderick T.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2367 DI 10.1158/1538-7445.AM2012-2367 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504355 ER PT J AU Kelly, AD Fountzilas, E Perez-Atayade, AR Goldsmith, J Konstantinopoulos, PA Francoeur, N Correll, M Rubio, R Hu, L Gebhardt, MC Quackenbush, J Spentzos, D AF Kelly, Andrew D. Fountzilas, Elena Perez-Atayade, Antonio R. Goldsmith, Jeffrey Konstantinopoulos, Panagiotis A. Francoeur, Nancy Correll, Mick Rubio, Renee Hu, Lan Gebhardt, Mark C. Quackenbush, John Spentzos, Dimitrios TI A microRNA activity map of human mesenchymal tumors: An integrative transcriptomic study SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kelly, Andrew D.; Fountzilas, Elena; Goldsmith, Jeffrey; Konstantinopoulos, Panagiotis A.; Francoeur, Nancy; Gebhardt, Mark C.; Spentzos, Dimitrios] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Perez-Atayade, Antonio R.] Childrens Hosp Boston, Boston, MA USA. [Correll, Mick; Rubio, Renee; Hu, Lan; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4941 DI 10.1158/1538-7445.AM2012-4941 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701604283 ER PT J AU Kim, J Loda, MF Freeman, MR AF Kim, Jayoung Loda, Massimo F. Freeman, Michael R. TI The ubiquitin-specific protease USP2a targets cyclin A1: A potential role in bladder cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kim, Jayoung; Freeman, Michael R.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Kim, Jayoung; Freeman, Michael R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Loda, Massimo F.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2188 DI 10.1158/1538-7445.AM2012-2188 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606169 ER PT J AU Koch, M Bowen, JA Galanis, A Gregory, M Ksander, BR Kreyosky, MK AF Koch, Margaret Bowen, Jeffery A. Galanis, Allison Gregory, Meredith Ksander, Bruce R. Kreyosky, Merideth K. TI Role of Survivin and small heat shock proteins in the chemoresistance of retinoblastoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Koch, Margaret; Bowen, Jeffery A.; Galanis, Allison; Kreyosky, Merideth K.] Bridgewater State Univ, Bridgewater, MA USA. [Gregory, Meredith; Ksander, Bruce R.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2257 DI 10.1158/1538-7445.AM2012-2257 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502100 ER PT J AU Kommajosyula, N Moreau, L D'Andrea, AD Shapiro, GI AF Kommajosyula, Naveen Moreau, Lisa D'Andrea, Alan D. Shapiro, Geoffrey I. TI Identification of factors governing sensitivity of NSCLC cell lines to inhibition of Poly (ADP-Ribose) Polymerase (PARP) SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kommajosyula, Naveen; Moreau, Lisa; D'Andrea, Alan D.; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2540 DI 10.1158/1538-7445.AM2012-2540 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701600230 ER PT J AU Kouri, FM Wu, YF Chin, L Stegh, AH AF Kouri, Fotini M. Wu, Yongfei Chin, Lynda Stegh, Alexander H. TI MicroRNA-182 acts as a chemosensitizer in GBM by repressing BcI2L12 SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kouri, Fotini M.; Wu, Yongfei; Stegh, Alexander H.] Northwestern Univ, Chicago, IL 60611 USA. [Chin, Lynda] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1107 DI 10.1158/1538-7445.AM2012-1107 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701503031 ER PT J AU Kozono, D Nitta, M Sampetrean, O Ng, K Merzon, D Kushwaha, D Zhu, KY Ligon, K Zhu, S Saya, H Chen, CC AF Kozono, David Nitta, Masayuki Sampetrean, Oltea Ng, Kimberly Merzon, Dmitry Kushwaha, Deepa Zhu, Kaya Ligon, Keith Zhu, Shan Saya, Hediyuki Chen, Clark C. TI A c-Myc driven threshold model of tumor initiating in glioblastoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kozono, David; Nitta, Masayuki; Ng, Kimberly; Merzon, Dmitry; Kushwaha, Deepa; Zhu, Kaya; Ligon, Keith; Zhu, Shan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sampetrean, Oltea; Saya, Hediyuki] Keio Univ, Tokyo, Japan. [Chen, Clark C.] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5218 DI 10.1158/1538-7445.AM2012-5218 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505080 ER PT J AU Kuhn, HE Orth, J Weissleder, R Mitchison, T AF Kuhn, Hallie E. Orth, James Weissleder, Ralph Mitchison, Timothy TI Innate immunity in taxol-mediated tumor regression SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kuhn, Hallie E.; Orth, James; Mitchison, Timothy] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 405 DI 10.1158/1538-7445.AM2012-405 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505459 ER PT J AU Kulkarni-Datar, KS Growdon, WB Ferguson, JA MacDougall, JR Foster, R Rueda, BR AF Kulkarni-Datar, Kashmira S. Growdon, Whitfield B. Ferguson, Jeanne A. MacDougall, John R. Foster, Rosemary Rueda, Bo R. TI Hedgehog pathway inhibition delays regrowth of ovarian cancer following paclitaxel and carboplatinum only if initiated immediately after completion of chemotherapy SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kulkarni-Datar, Kashmira S.; Growdon, Whitfield B.; Foster, Rosemary; Rueda, Bo R.] Massachsetts Gen Hosp, Boston, MA USA. [Ferguson, Jeanne A.; MacDougall, John R.] Infin Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3285 DI 10.1158/1538-7445.AM2012-3285 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504313 ER PT J AU Kulkarni-Datar, KS Orsulic, S Foster, R Rueda, BR AF Kulkarni-Datar, Kashmira S. Orsulic, Sandra Foster, Rosemary Rueda, Bo R. TI Ovarian cancer tumor initiating cells persist after paclitaxel and carboplatinum treatment in vivo SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kulkarni-Datar, Kashmira S.; Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Orsulic, Sandra] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3474 DI 10.1158/1538-7445.AM2012-3474 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502093 ER PT J AU Kumar, R Kulkarni, A Nagesha, D Cormack, R Makrigiorgos, M Sridhar, S AF Kumar, Rajiv Kulkarni, Apurva Nagesha, Dattatri Cormack, Robert Makrigiorgos, Mike Sridhar, Srinivas TI Nanocoated brachytherapy spacers eluting radiosensitizers for biological in situ image-guided radiation therapy of prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kumar, Rajiv; Kulkarni, Apurva; Nagesha, Dattatri; Sridhar, Srinivas] Northeastern Univ, Boston, MA 02115 USA. [Cormack, Robert] Brigham Womens Hosp, Boston, MA USA. [Makrigiorgos, Mike] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sridhar, Srinivas] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1473 DI 10.1158/1538-7445.AM2012-1473 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502085 ER PT J AU Kumar, R Patel, J Korideck, H Berbeco, RI Makrigiorgos, MG Sridhar, S AF Kumar, Rajiv Patel, Janki Korideck, Houari Berbeco, Ross I. Makrigiorgos, Mike G. Sridhar, Srinivas TI Comprehensive evaluation of PEGylated gold nanorods for two photon photoluminescence image guided radiation therapy enhancement SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kumar, Rajiv; Patel, Janki; Sridhar, Srinivas] Northeastern Univ, Boston, MA 02115 USA. [Korideck, Houari; Berbeco, Ross I.; Makrigiorgos, Mike G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sridhar, Srinivas] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1472 DI 10.1158/1538-7445.AM2012-1472 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502084 ER PT J AU Kuwahara, Y Mora-Blanco, EL Rogers, A Fletcher, CDM Roberts, CWM Weissman, BE Weissman, BE AF Kuwahara, Yasumichi Mora-Blanco, E. Lorena Rogers, Arlin Fletcher, Christopher D. M. Roberts, Charles W. M. Weissman, Bernard E. Weissman, Bernard E. TI Establishment and characterization of mouse malignant rhabdoid tumor cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kuwahara, Yasumichi] Kyoto Prefectural Univ Med, Kyoto, Japan. [Mora-Blanco, E. Lorena; Roberts, Charles W. M.] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA. [Mora-Blanco, E. Lorena; Roberts, Charles W. M.] Harvard Univ, Boston, MA 02115 USA. [Rogers, Arlin] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Fletcher, Christopher D. M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Weissman, Bernard E.; Weissman, Bernard E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1359 DI 10.1158/1538-7445.AM2012-1359 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504408 ER PT J AU Laviolette, LA Wilson, J Koller, J Zimmer, M Iliopoulos, O AF Laviolette, Laura A. Wilson, Jonas Koller, Julia Zimmer, Michael Iliopoulos, Othon TI Human FLCN delays cell cycle progression through late S and G2/M-phases: Effect of phosphorylation and tumor-associated mutations SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Laviolette, Laura A.; Wilson, Jonas; Koller, Julia; Zimmer, Michael; Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2171 DI 10.1158/1538-7445.AM2012-2171 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606151 ER PT J AU Lee, MS Liu, CY Su, L Wain, JC Mark, EJ Christiani, DC AF Lee, Mi-Sun Liu, Chen-yu Su, Li Wain, John C. Mark, Eugene J. Christiani, David C. TI Polymorphisms in the nucleotide excision repair genes, ERCC1 and ERCC2/XPD and carcinogen DNA adducts in human lung SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Lee, Mi-Sun; Liu, Chen-yu; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wain, John C.; Mark, Eugene J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4479 DI 10.1158/1538-7445.AM2012-4479 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701603468 ER PT J AU Leung, SLC Yeung, TL Balasubramanian, L Yip, KP Liu, JS Wong, KK Sood, AK Birrer, MJ Mok, SC AF Leung, Sze Lee Cecilia Yeung, Tsz-Lun Balasubramanian, Lavanya Yip, Kay-Pong Liu, Jinsong Wong, Kwong-Kwok Sood, Anil K. Birrer, Michael J. Mok, Samuel C. TI Novel stromal angiogenic factor MFAP5 in ovarian cancer progression SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Leung, Sze Lee Cecilia; Yeung, Tsz-Lun; Wong, Kwong-Kwok; Sood, Anil K.; Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Balasubramanian, Lavanya; Yip, Kay-Pong] Univ S Florida, Dept Mol Pharmacol & Physiol, Tampa, FL USA. [Liu, Jinsong] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4270 DI 10.1158/1538-7445.AM2012-4270 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505243 ER PT J AU Li, GM Ghosh, R Rivas, P Reddick, RL Kumar, AP AF Li, Guiming Ghosh, Rita Rivas, Paul Reddick, Robert Lee Kumar, Addanki Pratap TI Resveratrol induces autophagy in prostate cancer cells and intervention suppresses the progression of PIN in animals SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Li, Guiming; Ghosh, Rita; Rivas, Paul; Kumar, Addanki Pratap] UT Hlth Sci Ctr, Dept Urol, San Antonio, TX USA. [Reddick, Robert Lee] UT Hlth Sci Ctr, Dept Pathol, San Antonio, TX USA. [Kumar, Addanki Pratap] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2585 DI 10.1158/1538-7445.AM2012-2585 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701503400 ER PT J AU Liang, CH Marsit, CJ McClean, MD Nelson, HH Christensen, BC Haddad, RI Clark, JR Wein, RO Grillone, GA Houseman, EA Halec, G Waterboer, T Pawlita, M Krane, J Kelsey, KT AF Liang, Caihua Marsit, Carmen J. McClean, Michael D. Nelson, Heather H. Christensen, Brock C. Haddad, Robert I. Clark, John R. Wein, Richard O. Grillone, Gregory A. Houseman, E. Andres Halec, Gordana Waterboer, Tim Pawlita, Michael Krane, Jeffrey Kelsey, Karl T. TI Biomarkers of HPV in head and neck squamous cell carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Liang, Caihua; Kelsey, Karl T.] Brown Univ, Providence, RI 02912 USA. [Marsit, Carmen J.; Christensen, Brock C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [McClean, Michael D.] Boston Univ, Boston, MA 02215 USA. [Nelson, Heather H.] Univ Minnesota, Minneapolis, MN USA. [Haddad, Robert I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Clark, John R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wein, Richard O.] Tufts Univ, Boston, MA 02111 USA. [Grillone, Gregory A.] Boston Univ, Med Ctr, Boston, MA USA. [Houseman, E. Andres] Oregon State Univ, Corvallis, OR 97331 USA. [Halec, Gordana; Waterboer, Tim; Pawlita, Michael] Deutsch Krebsforschungszentrum, Heidelberg, Germany. [Krane, Jeffrey] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Waterboer, Tim/G-1252-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4497 DI 10.1158/1538-7445.AM2012-4497 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602028 ER PT J AU Liao, R Hammerman, P Sivachenko, A Greulich, H Getz, G Liu, QS Gray, N Meyerson, M AF Liao, Rachel Hammerman, Peter Sivachenko, Andrey Greulich, Heidi Getz, Gad Liu, Qingsong Gray, Nathanael Meyerson, Matthew TI FGFR3 as a therapeutic target in squamous cell lung carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Liao, Rachel; Hammerman, Peter; Greulich, Heidi; Liu, Qingsong; Gray, Nathanael; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sivachenko, Andrey; Getz, Gad] Broad Inst Harvard & MIT, Cambridge, MA USA. OI Liao, Rachel/0000-0002-7830-1976 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2 DI 10.1158/1538-7445.AM2012-2 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701604384 ER PT J AU Lin, JHL Zhang, SM Rexrode, K Manson, J Andrew, C Wu, KN Tworoger, S Hankinson, S Fuchs, C Gaziano, M Buring, J Giovannucci, E AF Lin, Jennifer-Hsiang-Ling Zhang, Shumin Rexrode, Kathy Manson, JoAnn Andrew, Chan Wu, Kana Tworoger, Shelley Hankinson, Susan Fuchs, Charles Gaziano, Michael Buring, Julie Giovannucci, Edward TI A prospective evaluation of circulating sex hormones in relation to colorectal cancer risk in men and women SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Lin, Jennifer-Hsiang-Ling; Zhang, Shumin; Rexrode, Kathy; Manson, JoAnn; Andrew, Chan; Tworoger, Shelley; Hankinson, Susan; Gaziano, Michael; Buring, Julie] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wu, Kana; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Fuchs, Charles] Dana Farber Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-338 DI 10.1158/1538-7445.AM2012-LB-338 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701603246 ER PT J AU Lin, L Bass, AJ Lockwood, WW Wang, ZW Silvers, AL Thomas, DG Chang, AC Lin, J Orringer, MB Li, WQ Glover, TW Giordano, TJ Lam, WL Meyerson, ML Beer, DG AF Lin, Lin Bass, Adam J. Lockwood, William W. Wang, Zhuwen Silvers, Amy L. Thomas, Dafydd G. Chang, Andrew C. Lin, Jules Orringer, Mark B. Li, Weiquan Glover, Thomas W. Giordano, Thomas J. Lam, Wan L. Meyerson, Matthew L. Beer, David G. TI Amplification and activation of GATA6 sustain oncogenic lineage-survival in esophageal adenocarcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Lin, Lin; Wang, Zhuwen; Silvers, Amy L.; Thomas, Dafydd G.; Chang, Andrew C.; Lin, Jules; Orringer, Mark B.; Li, Weiquan; Glover, Thomas W.; Giordano, Thomas J.; Beer, David G.] Univ Michigan, Ann Arbor, MI 48109 USA. [Bass, Adam J.; Meyerson, Matthew L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Lockwood, William W.; Lam, Wan L.] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2966 DI 10.1158/1538-7445.AM2012-2966 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501148 ER PT J AU Liu, SY Kharbanda, S Kufe, D Stone, R AF Liu, Suiyang Kharbanda, Surender Kufe, Donald Stone, Richard TI Targeting the MUC1-C oncoprotein blocks activation of FLT-3/ITD and induces death of acute myeloid leukemia cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Liu, Suiyang; Kharbanda, Surender; Kufe, Donald; Stone, Richard] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 173 DI 10.1158/1538-7445.AM2012-173 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606110 ER PT J AU Liu, Y Cowley, GS Cohoon, TJ Root, DE Kwok-kin, W AF Liu, Yan Cowley, Glenn S. Cohoon, Travis J. Root, David E. Kwok-kin, Wong TI Identification of DTYMK and CHEK1 as therapeutic targets in LKB1 mutant non-small cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Liu, Yan; Cohoon, Travis J.; Kwok-kin, Wong] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cowley, Glenn S.; Root, David E.] Broad Inst, Boston, MA USA. NR 0 TC 0 Z9 0 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 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-260 DI 10.1158/1538-7445.AM2012-LB-260 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602407 ER PT J AU Ma, J Giovannucci, E Nguyen, PL Qiu, WL Chavarro, J Rosner, B Cook, NR Platz, EA Gaziano, JM Pollak, M Stampfer, MJ AF Ma, Jing Giovannucci, Edward Nguyen, Paul L. Qiu, Weiliang Chavarro, Jorge Rosner, Bernard Cook, Nancy R. Platz, Elizabeth A. Gaziano, J. Michael Pollak, Michael Stampfer, Meir J. TI Energetic risk and prostate cancer-specific and all-cause mortality in two large cohorts of men with localized prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ma, Jing; Qiu, Weiliang; Rosner, Bernard; Cook, Nancy R.; Gaziano, J. Michael; Stampfer, Meir J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Giovannucci, Edward; Chavarro, Jorge] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Nguyen, Paul L.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Pollak, Michael] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Pollak, Michael] McGill Univ, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4501 DI 10.1158/1538-7445.AM2012-4501 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602032 ER PT J AU Ma, WX Gutierrez, A Wei, P Sadarangani, A Goff, DJ Shih, AY Court, AC Jiang, QF Leu, H Wall, RH Crews, LA Look, AT Jamieson, CHM AF Ma, Wenxue Gutierrez, Alejandro Wei, Ping Sadarangani, Anil Goff, Daniel J. Shih, Alice Y. Court, Angela C. Jiang, Qingfei Leu, Heather Wall, Russell H. Crews, Leslie A. Look, A. Thomas Jamieson, Catriona H. M. TI NOTCH1 signaling is essential for leukemia initiating cell self-renewal in T-ALL SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ma, Wenxue; Sadarangani, Anil; Goff, Daniel J.; Shih, Alice Y.; Court, Angela C.; Jiang, Qingfei; Leu, Heather; Wall, Russell H.; Crews, Leslie A.; Jamieson, Catriona H. M.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Gutierrez, Alejandro; Look, A. Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wei, Ping] Pfizer Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1011 DI 10.1158/1538-7445.AM2012-1011 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505183 ER PT J AU Martin, NE Gerke, T Loda, M Stampfer, M Finn, S Rider, J Mucci, LA AF Martin, Neil E. Gerke, Travis Loda, Massimo Stampfer, Meir Finn, Stephen Rider, Jennifer Mucci, Lorelei A. TI Tumor adiponectin signaling underlies the association between obesity and lethal outcome in prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Martin, Neil E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gerke, Travis; Stampfer, Meir; Rider, Jennifer; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Loda, Massimo] Dana Farber Canc Inst, Boston, MA 02115 USA. [Finn, Stephen] Trinity Coll Dublin, Dublin, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5166 DI 10.1158/1538-7445.AM2012-5166 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502258 ER PT J AU Metallo, C Gameiro, P Heiden, MV Ilioupoulos, O Stephanopoulos, G AF Metallo, Christian Gameiro, Paulo Heiden, Matthew Vander Ilioupoulos, Othon Stephanopoulos, Greg TI Reductive tricarboxylic acid metabolism of glutamine mediates lipogenesis under hypoxia SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Metallo, Christian] Univ Calif San Diego, La Jolla, CA 92093 USA. [Gameiro, Paulo; Heiden, Matthew Vander; Stephanopoulos, Greg] MIT, Cambridge, MA 02139 USA. [Ilioupoulos, Othon] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1001 DI 10.1158/1538-7445.AM2012-1001 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501129 ER PT J AU Metelo, AM Xiang, L Baker, R Burger, A Peterson, R Iliopoulos, O AF Metelo, Ana Marguerita Xiang, Li Baker, Rania Burger, Alexa Peterson, Randall Iliopoulos, Othon TI In vivo activity of small molecule HIF2 alpha inhibitors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Metelo, Ana Marguerita; Xiang, Li; Baker, Rania; Burger, Alexa; Peterson, Randall; Iliopoulos, Othon] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4253 DI 10.1158/1538-7445.AM2012-4253 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505164 ER PT J AU Michaud, DS Izard, J Wilhelm-Benartzi, C Riboli, E Bueno-de-Mesquita, B AF Michaud, Dominique S. Izard, Jacques Wilhelm-Benartzi, Charlotte Riboli, Elio Bueno-de-Mesquita, Bas CA EPIC Team TI Plasma antibodies to oral pathogen and commensals and risk of pancreatic cancer in a large European prospective cohort study SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Michaud, Dominique S.] Brown Univ, Providence, RI 02912 USA. [Izard, Jacques] Forsyth Inst, Boston, MA USA. [Wilhelm-Benartzi, Charlotte; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, London, England. [Bueno-de-Mesquita, Bas] Univ Med Ctr Utrecht, Utrecht, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-328 DI 10.1158/1538-7445.AM2012-LB-328 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701603113 ER PT J AU Mishra, DK Baird, BN Ott, HC Gibbons, DL Kurie, JM Kim, MP AF Mishra, Dhruva K. Baird, Brandi N. Ott, Harald C. Gibbons, Don L. Kurie, Jonathan M. Kim, Min P. TI Circulating tumor cells from perfusable tumor nodules grown on decellularized rat lung scaffold has mesenchymal characteristics SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Mishra, Dhruva K.; Kim, Min P.] Methodist Hosp, Res Inst, Houston, TX 77030 USA. [Baird, Brandi N.; Gibbons, Don L.; Kurie, Jonathan M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ott, Harald C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 345 DI 10.1158/1538-7445.AM2012-345 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505281 ER PT J AU Mishra, DK Shen, HF Mai, JH Ott, HC Baird, BN Kurie, JM Kim, MP AF Mishra, Dhruva K. Shen, Haifa Mai, Junhua Ott, Harald C. Baird, Brandi N. Kurie, Jonathan M. Kim, Min P. TI Ex vivo lung cancer nodule model shows efficacy of nanoparticle delivery SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Mishra, Dhruva K.; Shen, Haifa; Mai, Junhua; Kim, Min P.] Methodist Hosp, Res Inst, Houston, TX 77030 USA. [Ott, Harald C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Baird, Brandi N.; Kurie, Jonathan M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-112 DI 10.1158/1538-7445.AM2012-LB-112 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504189 ER PT J AU Morello, M Dudley, AC Schow, P Adam, RM Morley, S Mulholland, D Insabato, L Wu, H Klagsbrun, M Bhowmick, NA Rubin, MA D'Souza-Schorey, C Freeman, MR Di Vizio, D AF Morello, Matteo Dudley, Andrew C. Schow, Peter Adam, Rosalyn M. Morley, Samantha Mulholland, David Insabato, Luigi Wu, Hong Klagsbrun, Michael Bhowmick, Neil A. Rubin, Mark A. D'Souza-Schorey, Crislyn Freeman, Michael R. Di Vizio, Dolores TI MiRNA profiling of prostate cancer cell-derived large oncosomes identifies a signature of invasion and metastasis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Morello, Matteo; Bhowmick, Neil A.; Freeman, Michael R.; Di Vizio, Dolores] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Dudley, Andrew C.; Klagsbrun, Michael] Childrens Hosp Boston, Boston, MA USA. [Schow, Peter] Dana Farber Canc Ctr, Boston, MA USA. [Adam, Rosalyn M.; Morley, Samantha] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Mulholland, David; Wu, Hong] Univ Calif Los Angeles, Los Angeles, CA USA. [Insabato, Luigi] Univ Naples Federico II, Naples, Italy. [Rubin, Mark A.] Weill Cornell Med Coll, New York, NY USA. [D'Souza-Schorey, Crislyn] Univ Notre Dame, Notre Dame, IN 46556 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 430 DI 10.1158/1538-7445.AM2012-430 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701506043 ER PT J AU Moroco, JA Gray, NS Smithgall, TE AF Moroco, Jamie A. Gray, Nathanael S. Smithgall, Thomas E. TI Selective small-molecule kinase inhibitors of the c-Src:FAK complex SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Moroco, Jamie A.; Smithgall, Thomas E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 861 DI 10.1158/1538-7445.AM2012-861 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701603412 ER PT J AU Mortazavi, F Rettig, M AF Mortazavi, Fariborz (Fred) Rettig, Matthew TI PAK1 kinase promotes cell motility through CRK serine phosphorylation in non-small cell lung cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Mortazavi, Fariborz (Fred); Rettig, Matthew] Univ Calif Los Angeles, VA Greater LA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 228 DI 10.1158/1538-7445.AM2012-228 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501386 ER PT J AU Nakata, A Yamauchi, M Yamaguchi, R Kohno, T Nagasaki, M Shimamura, T Imoto, S Saito, A Ueno, K Hatanaka, Y Yoshida, R Higuchi, T Nomura, M Beer, DG Yokota, J Miyano, S Gotoh, N AF Nakata, Asuka Yamauchi, Mai Yamaguchi, Rui Kohno, Takashi Nagasaki, Masao Shimamura, Teppei Imoto, Seiya Saito, Ayumu Ueno, Kazuko Hatanaka, Yousuke Yoshida, Ryo Higuchi, Tomoyuki Nomura, Masaharu Beer, David G. Yokota, Jun Miyano, Satoru Gotoh, Noriko TI EGF receptor tyrosine kinase defines critical prognostic genes of stage IA lung adenocarcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Nakata, Asuka; Yamaguchi, Rui; Nagasaki, Masao; Shimamura, Teppei; Imoto, Seiya; Saito, Ayumu; Ueno, Kazuko; Hatanaka, Yousuke; Miyano, Satoru; Gotoh, Noriko] Univ Tokyo, Inst Med Sci, Tokyo, Japan. [Yamauchi, Mai] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yamauchi, Mai] Harvard Univ, Sch Med, Boston, MA USA. [Kohno, Takashi; Yokota, Jun] Natl Canc Ctr, Tokyo, Japan. [Yoshida, Ryo; Higuchi, Tomoyuki] Inst Stat Math, Tokyo, Japan. [Nomura, Masaharu] Tokyo Med Univ, Tokyo 1608402, Japan. [Beer, David G.] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-99 DI 10.1158/1538-7445.AM2012-LB-99 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501169 ER PT J AU Okumura, N Yamada, S Fuchs, BC Fujii, T Sugimoto, H Nomoto, S Takeda, S Tanabe, KK Kodera, Y Nakao, A AF Okumura, Norio Yamada, Suguru Fuchs, Bryan C. Fujii, Tsutomu Sugimoto, Hiroyuki Nomoto, Shuji Takeda, Shin Tanabe, Kenneth K. Kodera, Yasuhiro Nakao, Akimasa TI Clinical implication of epithelial to mesenchymal transition (EMT) in hepatocellular carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Okumura, Norio; Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Nomoto, Shuji; Takeda, Shin; Kodera, Yasuhiro] Nagoya Univ, Gradiate Sch Med, Nagoya, Aichi 4648601, Japan. [Fuchs, Bryan C.; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nakao, Akimasa] Nagoya Cent Hosp, Nagoya, Aichi, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3402 DI 10.1158/1538-7445.AM2012-3402 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504029 ER PT J AU Palescandolo, E Jones, R Raza, A Sunkavalli, A Brastianos, PK Ducar, M Go, C Roden, C Hatton, C Hanna, M Mills, A Adusumilli, R Kumar, P Meyerson, ML William, HC MacConaill, L Van Hummelen, P AF Palescandolo, Emanuele Jones, Robert Raza, Alina Sunkavalli, Ashwini Brastianos, Priscilla K. Ducar, Matthew Go, Christina Roden, Christine Hatton, Charles Hanna, Megan Mills, Adri Adusumilli, Ravali Kumar, Prateek Meyerson, Matthew L. William, Hahn C. MacConaill, Laura Van Hummelen, Paul TI Can DNA from archived formalin-fixed paraffin embedded (FFPE) cancer tissues be used for somatic mutation analysis in next generation sequencing SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Palescandolo, Emanuele; Jones, Robert; Raza, Alina; Sunkavalli, Ashwini; Brastianos, Priscilla K.; Ducar, Matthew; Go, Christina; Roden, Christine; Hatton, Charles; Hanna, Megan; Mills, Adri; Adusumilli, Ravali; Kumar, Prateek; Meyerson, Matthew L.; William, Hahn C.; MacConaill, Laura; Van Hummelen, Paul] DFCI, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3178 DI 10.1158/1538-7445.AM2012-3178 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606178 ER PT J AU Panchamoorthy, G Raina, D Rehan, H Kharbanda, S Kufe, D AF Panchamoorthy, Govind Raina, Deepak Rehan, Hala Kharbanda, Surender Kufe, Donald TI A MUC1-C oncoprotein soluble decoy receptor effectively suppresses the growth of human breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Panchamoorthy, Govind; Raina, Deepak; Rehan, Hala; Kharbanda, Surender] Genus Oncol LLC, Boston, MA USA. [Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1819 DI 10.1158/1538-7445.AM2012-1819 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701604128 ER PT J AU Park, C Lee, IS Nitsche, C Gerloff, A Go, VLW Grippo, PJ Pandol, SJ Gukovskaya, AS Edderkaoui, M AF Park, ChangHwan Lee, In Soek Nitsche, Claudia Gerloff, Andreas Go, Vay Liang W. Grippo, Paul J. Pandol, Stephen J. Gukovskaya, Anna S. Edderkaoui, Mouad TI Novel model of pancreatic cancer induced by smoking compound NNK SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Park, ChangHwan; Lee, In Soek; Nitsche, Claudia; Gerloff, Andreas; Go, Vay Liang W.; Pandol, Stephen J.; Gukovskaya, Anna S.; Edderkaoui, Mouad] Univ Calif Los Angeles, Los Angeles, CA USA. [Park, ChangHwan; Lee, In Soek; Nitsche, Claudia; Gerloff, Andreas; Go, Vay Liang W.; Pandol, Stephen J.; Gukovskaya, Anna S.; Edderkaoui, Mouad] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Grippo, Paul J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1337 DI 10.1158/1538-7445.AM2012-1337 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504383 ER PT J AU Patnaik, A Courtney, K Robichaud, K Bellinger, G Nardella, C Signoretti, S Wooster, R Pandolfi, PP Cantley, L AF Patnaik, Akash Courtney, Kevin Robichaud, Kyle Bellinger, Gary Nardella, Caterina Signoretti, Sabina Wooster, Richard Pandolfi, Pier Paolo Cantley, Lewis TI Effective use of PI3K/MTOR and MEK inhibitors prior to hormone ablative therapy in PTEN-loss driven murine prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Patnaik, Akash; Pandolfi, Pier Paolo; Cantley, Lewis] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Courtney, Kevin; Signoretti, Sabina] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Robichaud, Kyle; Bellinger, Gary; Nardella, Caterina] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wooster, Richard] GlaxoSmithKline, Collegeville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-365 DI 10.1158/1538-7445.AM2012-LB-365 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701500235 ER PT J AU Perets, R Muto, KW Bijron, JG Kenneth, CT Poole, BB Crum, CP Dinulescu, DM Drapkin, R AF Perets, Ruth Muto, Katherine W. Bijron, Jonathan G. Kenneth, Chin T. Poole, Barish B. Crum, Christopher P. Dinulescu, Daniela M. Drapkin, Ronny TI A genetically engineered mouse model for high grade serous "ovarian" carcinoma arising in the fallopian tube SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Perets, Ruth; Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. [Muto, Katherine W.; Bijron, Jonathan G.; Kenneth, Chin T.; Poole, Barish B.; Crum, Christopher P.; Dinulescu, Daniela M.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3292 DI 10.1158/1538-7445.AM2012-3292 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504321 ER PT J AU Permuth-Wey, J Lin, HY Tsai, YY Chen, ZH Chen, YA Barnholtz-Sloan, J Birrer, MJ Chanock, S Cramer, DW Cunningham, JM Fenstermacher, D Fridley, B Garcia-Closas, M Gayther, SA Gentry-Maharaj, A Gonzalez-Bosquet, J Iversen, E Jim, H McLaughlin, J Menon, U Monteiro, A Narod, SA Phelan, CM Ramus, S Risch, H Song, H Sutphen, R Terry, KL Tyrer, J Vierkant, RA Wentzensen, N Lancaster, JM Cheng, JQ Berchuk, A Pharoah, PDP Schildkraut, JM Goode, EL Sellers, TA AF Permuth-Wey, Jennifer Lin, Hui-Yi Tsai, Ya-Yu Chen, Zhihua Chen, Y. Ann Barnholtz-Sloan, Jill Birrer, Micheal J. Chanock, Stephen Cramer, Daniel W. Cunningham, Julie M. Fenstermacher, David Fridley, Brooke Garcia-Closas, Montserrat Gayther, Simon A. Gentry-Maharaj, Alexandra Gonzalez-Bosquet, Jesus Iversen, Edwin Jim, Heather McLaughlin, John Menon, Usha Monteiro, Alvaro Narod, Steven A. Phelan, Catherine M. Ramus, Susan Risch, Harvey Song, Honglin Sutphen, Rebecca Terry, Kathryn L. Tyrer, Jonathan Vierkant, Robert A. Wentzensen, Nicolas Lancaster, Johnathan M. Cheng, Jin Q. Berchuk, Andrew Pharoah, Paul D. P. Schildkraut, Joellen M. Goode, Ellen L. Sellers, Thomas A. TI MicroRNA binding site polymorphisms influence ovarian cancer risk in the collaborative oncological gene-environment study SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Permuth-Wey, Jennifer; Lin, Hui-Yi; Tsai, Ya-Yu; Chen, Zhihua; Chen, Y. Ann; Fenstermacher, David; Gonzalez-Bosquet, Jesus; Jim, Heather; Monteiro, Alvaro; Phelan, Catherine M.; Lancaster, Johnathan M.; Cheng, Jin Q.; Sellers, Thomas A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Barnholtz-Sloan, Jill] Case Comprehens Canc Ctr, Cleveland, OH USA. [Birrer, Micheal J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chanock, Stephen; Wentzensen, Nicolas] NIH, Rockville, MD USA. [Cramer, Daniel W.; Terry, Kathryn L.] Brigham Womens Hosp, Boston, MA USA. [Cunningham, Julie M.; Fridley, Brooke; Vierkant, Robert A.; Goode, Ellen L.] Mayo Clin, Coll Med, Rochester, MN USA. [Garcia-Closas, Montserrat] Inst Canc Res, London SW3 6JB, England. [Garcia-Closas, Montserrat] Breakthrough Breast Canc Res Ctr, London, England. [Gayther, Simon A.; Ramus, Susan] Univ So Calif, Los Angeles, CA USA. [Gentry-Maharaj, Alexandra; Menon, Usha] UCL, EGA Inst Womens Hlth, London, England. [Iversen, Edwin] Duke Univ, Dept Stat Sci, Durham, NC USA. [McLaughlin, John] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Narod, Steven A.] Ctr Res Womens Hlth, Toronto, ON, Canada. [Risch, Harvey] Yale Univ, Sch Med, New Haven, CT USA. [Song, Honglin; Tyrer, Jonathan; Pharoah, Paul D. P.] Univ Cambridge, Cambridge, England. [Sutphen, Rebecca] Univ S Florida, Tampa, FL USA. [Berchuk, Andrew; Schildkraut, Joellen M.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2927 DI 10.1158/1538-7445.AM2012-2927 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701602478 ER PT J AU Perry, JA Orkin, S AF Perry, Jennifer A. Orkin, Stuart TI A genome-wide RNAi screen implicates histone deacetylases as a therapeutic target for osteosarcoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Perry, Jennifer A.; Orkin, Stuart] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4234 DI 10.1158/1538-7445.AM2012-4234 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505143 ER PT J AU Polyak, K AF Polyak, Kornelia TI Intratumor diversity in breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Polyak, Kornelia] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA SY17-01 DI 10.1158/1538-7445.AM2012-SY17-01 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701503456 ER PT J AU Poulikakos, PI Persaud, Y Janakiraman, M Kong, XJ Ng, C Moriceau, G Shi, HB Atefi, M Titz, B Gabay, MT Salton, M Dahlman, KB Tadi, M Wargo, JA Flaherty, KT Kelley, MC Misteli, T Chapman, PB Sosman, JA Graeber, TG Ribas, A Lo, RS Rosen, N Solit, DB AF Poulikakos, Poulikos I. Persaud, Yogindra Janakiraman, Manickam Kong, Xiangju Ng, Charles Moriceau, Gatien Shi, Hubing Atefi, Mohammad Titz, Bjoern Gabay, May Tal Salton, Maayan Dahlman, Kimberly B. Tadi, Madhavi Wargo, Jennifer A. Flaherty, Keith T. Kelley, Mark C. Misteli, Tom Chapman, Paul B. Sosman, Jeffrey A. Graeber, Thomas G. Ribas, Antoni Lo, Roger S. Rosen, Neal Solit, David B. TI RAS-independent dimerization of BRAF(V600E) splicing variants promotes resistance to RAF inhibitors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Poulikakos, Poulikos I.; Persaud, Yogindra; Janakiraman, Manickam; Gabay, May Tal; Tadi, Madhavi; Chapman, Paul B.; Rosen, Neal; Solit, David B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kong, Xiangju; Ng, Charles; Moriceau, Gatien; Shi, Hubing; Atefi, Mohammad; Titz, Bjoern; Graeber, Thomas G.; Ribas, Antoni; Lo, Roger S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Salton, Maayan; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. [Dahlman, Kimberly B.; Kelley, Mark C.; Sosman, Jeffrey A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Wargo, Jennifer A.; Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-428 DI 10.1158/1538-7445.AM2012-LB-428 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501094 ER PT J AU Qi, L Xu, CX Sarosieki, K Ligon, A Rodig, S Wong, KK Letai, A Shapiro, GI AF Qi, Li Xu, Chunxiao Sarosieki, Kristopher Ligon, Azra Rodig, Scott Wong, Kwok-Kin Letai, Anthony Shapiro, Geoffrey I. TI A subset of small cell lung cancer (SCLC) cell lines is Mcl-1-dependent and responds to cyclin-dependent kinase (cdk)9 inhibition in vitro and in vivo SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Qi, Li; Xu, Chunxiao; Sarosieki, Kristopher; Ligon, Azra; Wong, Kwok-Kin; Letai, Anthony; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodig, Scott] Brigham & Womens Hosp, Boston, MA 02115 USA. OI wong, kwok kin/0000-0001-6323-235X NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2016 DI 10.1158/1538-7445.AM2012-2016 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606024 ER PT J AU Raina, D Ahmad, R Rajabi, H Panchamoorthy, G Kufe, DW Kharbanda, S AF Raina, Deepak Ahmad, Rehan Rajabi, Hasan Panchamoorthy, Govind Kufe, Donald W. Kharbanda, Surender TI Targeting cysteine-mediated dimerization of the MUC1-C oncoprotein in human cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Raina, Deepak; Panchamoorthy, Govind; Kharbanda, Surender] Genus Oncol LLC, Boston, MA USA. [Ahmad, Rehan; Rajabi, Hasan; Kufe, Donald W.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 160 DI 10.1158/1538-7445.AM2012-160 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606096 ER PT J AU Raina, D Kharbanda, S Kufe, D AF Raina, Deepak Kharbanda, Surender Kufe, Donald TI Targeting the MUC1-C oncoprotein synergistically enhances cytotoxicity of breast carcinoma cells in combination with PI3K inhibitors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Raina, Deepak; Kharbanda, Surender] Genus Oncol LLC, Boston, MA USA. [Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2243 DI 10.1158/1538-7445.AM2012-2243 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501355 ER PT J AU Ramsey, MR Wilson, C Ory, B Rothenberg, SM Faquin, W Mills, AA Ellisen, LW AF Ramsey, Matthew R. Wilson, Catherine Ory, Benjamin Rothenberg, S. Michael Faquin, William Mills, Alea A. Ellisen, Leif W. TI p63 functions as an essential oncogene in squamous cell carcinoma in vivo and is required for tumor maintenance SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ramsey, Matthew R.; Wilson, Catherine; Ory, Benjamin; Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Rothenberg, S. Michael; Faquin, William] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mills, Alea A.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1306 DI 10.1158/1538-7445.AM2012-1306 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502412 ER PT J AU Rand, KA Conti, DV Haiman, CA Van Den Berg, DJ Birmann, BM De Roos, AJ Severson, RK Gebregziabher, M Ailawadhi, S Morbacher, A Lieber, MR Wang, SS Bernstein, L Edlund, CK Rothman, N Chanock, SJ Kolonel, LN Colditz, GA Munshi, N Anderson, KC Cozen, W AF Rand, Kristin A. Conti, David V. Haiman, Christopher A. Van Den Berg, David J. Birmann, Brenda M. De Roos, Anneclaire J. Severson, Richard K. Gebregziabher, Mulugeta Ailawadhi, Sikander Morbacher, Ann Lieber, Michael R. Wang, Sophia S. Bernstein, Leslie Edlund, Christopher K. Rothman, Nathaniel Chanock, Stephen J. Kolonel, Laurence N. Colditz, Graham A. Munshi, Nikhil Anderson, Kenneth C. Cozen, Wendy TI Polymorphisms in DNA repair genes and risk of multiple myeloma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Rand, Kristin A.; Conti, David V.; Haiman, Christopher A.; Lieber, Michael R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Van Den Berg, David J.; Cozen, Wendy] Univ So Calif, Dept Prevent Med, Ctr Comprehens Canc, Los Angeles, CA 90089 USA. [Van Den Berg, David J.; Cozen, Wendy] Univ So Calif, Dept Pathol, Ctr Comprehens Canc, Los Angeles, CA 90089 USA. [Birmann, Brenda M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Birmann, Brenda M.] Harvard Univ, Sch Med, Boston, MA USA. [De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Ailawadhi, Sikander; Morbacher, Ann] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Div Hematol,Dept Med, Los Angeles, CA 90033 USA. [Wang, Sophia S.; Bernstein, Leslie] City Hope Natl Med Ctr, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. [Edlund, Christopher K.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Rothman, Nathaniel; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. [Colditz, Graham A.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Munshi, Nikhil; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jeroma Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2634 DI 10.1158/1538-7445.AM2012-2634 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701602262 ER PT J AU Rao, SY Lee, S Guitierrez, A Perrigoue, JJ Thapa, R Tu, ZG Jeffers, J Rhodes, M Hunger, S Downing, J Zhang, RG Balachandran, S Zambetti, G Testa, J Look, AT Wiest, D AF Rao, Shuyun Lee, Sangyun Guitierrez, Alejandro Perrigoue, Jacqueline Jacqueline Thapa, Roshan Tu, Zhigang Jeffers, John Rhodes, Michele Hunger, Stephen Downing, James Zhang, Rugang Balachandran, Siddharth Zambetti, Gerard Testa, Joseph Look, A. Thomas Wiest, David TI Inactivation of ribosomal protein L22 promotes transformation by induction of Lin28B SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Rao, Shuyun; Lee, Sangyun; Perrigoue, Jacqueline Jacqueline; Thapa, Roshan; Tu, Zhigang; Rhodes, Michele; Zhang, Rugang; Balachandran, Siddharth; Testa, Joseph; Wiest, David] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Guitierrez, Alejandro; Look, A. Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jeffers, John; Downing, James; Zambetti, Gerard] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Hunger, Stephen] Univ Colorado Denver, Sch Med, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1353 DI 10.1158/1538-7445.AM2012-1353 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504400 ER PT J AU Richardson, KA Wu, G Kuang, Y Wang, LL Legendre, B Lin, R Shi, YG Eastlake, P Cayre, Y Janne, P Distel, R AF Richardson, Katherine A. Wu, Grant Kuang, Yanan Wang, Lilin Legendre, Benjamin Lin, Rui Shi, Yanggu Eastlake, Phil Cayre, Yvon Janne, Pasi Distel, Robert TI Mutational analysis in circulating tumor cells (CTC):ScreenCell MB Filtration Unit and ICE COLD-PCR SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Richardson, Katherine A.; Wu, Grant; Legendre, Benjamin; Lin, Rui; Shi, Yanggu; Eastlake, Phil] Transgenomic Inc, Omaha, NE USA. [Kuang, Yanan; Wang, Lilin; Janne, Pasi; Distel, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cayre, Yvon] ScreenCell, Paris, France. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2090 DI 10.1158/1538-7445.AM2012-2090 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701605216 ER PT J AU Roberts, NJ Jiao, YC Yu, J Kopelovich, L Petersen, GM Bondy, M Gallinger, S Schwartz, AG Syngai, S Cote, ML Axilbund, J Schulick, R Ali, SZ Eshleman, JR Velculescu, V Goggins, M Vogelstein, B Papadopoulous, N Hruban, RH Kinzler, KW Klein, AP AF Roberts, Nicholas J. Jiao, Yuchen Yu, Jun Kopelovich, Levy Petersen, Gloria M. Bondy, Melissa Gallinger, Steven Schwartz, Ann G. Syngai, Sapna Cote, Michele L. Axilbund, Jennifer Schulick, Richard Ali, Syed Z. Eshleman, James R. Velculescu, Victor Goggins, Michael Vogelstein, Bert Papadopoulous, Nikolas Hruban, Ralph H. Kinzler, Kenneth W. Klein, Alison P. TI Genome-wide sequencing identifies ATM as a pancreatic cancer susceptibility gene SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Roberts, Nicholas J.; Jiao, Yuchen; Yu, Jun; Axilbund, Jennifer; Schulick, Richard; Ali, Syed Z.; Eshleman, James R.; Velculescu, Victor; Goggins, Michael; Vogelstein, Bert; Papadopoulous, Nikolas; Hruban, Ralph H.; Kinzler, Kenneth W.; Klein, Alison P.] Johns Hopkins Univ, Baltimore, MD USA. [Kopelovich, Levy] NCI, Bethesda, MD 20892 USA. [Petersen, Gloria M.] Mayo Clin, Rochester, MN USA. [Bondy, Melissa] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Schwartz, Ann G.; Cote, Michele L.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Syngai, Sapna] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2628 DI 10.1158/1538-7445.AM2012-2628 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602255 ER PT J AU Rodig, S Sequist, LV Schiller, JH Chen, YP Halim, A Waghorne, C Zahir, H Schwartz, B AF Rodig, Scott Sequist, Lecia V. Schiller, Joan H. Chen, Yinpu Halim, Abdel Waghorne, Carol Zahir, Hamim Schwartz, Brian TI An exploratory biomarker analysis evaluating the effect of the c-MET inhibitor tivantinib (ARQ 197) and erlotinib in NSCLC patients in a randomized, double blinded phase 2 study SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Rodig, Scott] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rodig, Scott; Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Harold C Simmons Canc Ctr, Dallas, TX 75390 USA. [Chen, Yinpu; Waghorne, Carol; Schwartz, Brian] ArQule Inc, Woburn, MA USA. [Halim, Abdel; Zahir, Hamim] Daiichi Sankyo Pharma Dev, Edison, NJ USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1729 DI 10.1158/1538-7445.AM2012-1729 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601051 ER PT J AU Rodrik-Outmezguine, VS Chandarlapaty, S Pagano, NC Poulikakos, PI Scaltriti, M Baselga, J Guichard, S Rosen, N AF Rodrik-Outmezguine, Vanessa S. Chandarlapaty, Sarat Pagano, Nen C. Poulikakos, Poulikos I. Scaltriti, Maurizio Baselga, Jose Guichard, Sylvie Rosen, Neal TI mTOR kinase inhibition relieves feedback suppression of receptor tyrosine kinase leading to a biphasic regulation of AKT signaling in breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Rodrik-Outmezguine, Vanessa S.; Chandarlapaty, Sarat; Pagano, Nen C.; Poulikakos, Poulikos I.; Rosen, Neal] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Scaltriti, Maurizio; Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Guichard, Sylvie] AstraZeneca, Macclesfield, Cheshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-20 DI 10.1158/1538-7445.AM2012-LB-20 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501202 ER PT J AU Rothenberg, SM Wargo, J Juric, D Corcoran, RB Winokur, D Flaherty, KT Baselga, J Maheswaran, S Engelman, JA Haber, DA AF Rothenberg, Stephen M. Wargo, Jennifer Juric, Dejan Corcoran, Ryan B. Winokur, Daniel Flaherty, Keith T. Baselga, Jose Maheswaran, Shyamala Engelman, Jeffrey A. Haber, Daniel A. TI Real-time molecular imaging of targeted therapies in patient-derived tumor cells by quantitative immunofluorescence microscopy SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Rothenberg, Stephen M.; Juric, Dejan; Corcoran, Ryan B.; Winokur, Daniel; Maheswaran, Shyamala; Engelman, Jeffrey A.; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Wargo, Jennifer; Flaherty, Keith T.; Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2446 DI 10.1158/1538-7445.AM2012-2446 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505377 ER PT J AU Schmitt, AD Fuchs, BC Wei, L Tanabe, KK Lanuti, M AF Schmitt, Anthony D. Fuchs, Bryan C. Wei, Lan Tanabe, Kenneth K. Lanuti, Michael TI Characterizing TGF beta 1-inducible EMT models in NSCLC helps define critical EMT-associated genes for therapeutic targeting SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Schmitt, Anthony D.; Fuchs, Bryan C.; Wei, Lan; Tanabe, Kenneth K.; Lanuti, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4610 DI 10.1158/1538-7445.AM2012-4610 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601381 ER PT J AU Shaw, AT Ghizdavescu, D Jain, M Volovat, C Subramaniam, D Shuster, D Jin, XP Dutta, D Pai, S von Roemeling, R AF Shaw, Alice T. Ghizdavescu, Doru Jain, Minish Volovat, Constantin Subramaniam, Deepa Shuster, Dale Jin, Xiaoping Dutta, Dipen Pai, Seema von Roemeling, Reinhard TI Randomized phase 2 study of efatutazone in combination with carboplatin and paclitaxel as first-line therapy for metastatic non-small cell lung cancer (NSCLC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Ghizdavescu, Doru] Ploiesti Sectia Oncol Med, Ploiesti, Romania. [Jain, Minish] Noble Hosp, Pune, Maharashtra, India. [Volovat, Constantin] Ctr Oncol Med, Iasi, Romania. [Subramaniam, Deepa] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Shuster, Dale; Jin, Xiaoping; Dutta, Dipen; von Roemeling, Reinhard] Daiichi Sankyo, Daiichi Sankyo Pharma Dev, Edison, NJ USA. [Pai, Seema] Daiichi Sankyo, Daiichi Sankyo India Dev, Gurgaon, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4606 DI 10.1158/1538-7445.AM2012-4606 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601377 ER PT J AU Singh, A Sweeney, MF Yu, M Burger, A Greninger, P Benes, C Haber, DA Settleman, J AF Singh, Anurag Sweeney, Michael F. Yu, Min Burger, Alexa Greninger, Patricia Benes, Cyril Haber, Daniel A. Settleman, Jeff TI TAK1 (MAP3K7) inhibition promotes apoptosis in KRAS dependent colon cancers SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Singh, Anurag; Sweeney, Michael F.; Yu, Min; Burger, Alexa; Greninger, Patricia; Benes, Cyril; Settleman, Jeff] Massachusetts Gen Hosp, Charlestown, MA USA. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-427 DI 10.1158/1538-7445.AM2012-LB-427 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602305 ER PT J AU Sioletic, S Sicinska, E Loda, M Fletcher, CDM Fletcher, JA Demetri, GD Snyder, EL AF Sioletic, Stefano Sicinska, Ewa Loda, Massimo Fletcher, Christopher D. M. Fletcher, Jonathan A. Demetri, George D. Snyder, Eric L. TI Genomic amplification of c-Jun activates genes that promote proliferation and cell migration in liposarcoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Sioletic, Stefano; Sicinska, Ewa; Loda, Massimo; Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fletcher, Christopher D. M.; Fletcher, Jonathan A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Snyder, Eric L.] MIT, Robert Koch Inst, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-270 DI 10.1158/1538-7445.AM2012-LB-270 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501255 ER PT J AU Stransky, N Kryukov, GV Caponigro, G Barretina, J Venkatesan, K Margolin, AA Wilson, CJ Lehar, J Jones, MD Palescandolo, E Sougnez, C Onofrio, RC MacConaill, L Ardlie, K Golub, TR Morrissey, M Selers, WR Schlegel, R Garraway, LA AF Stransky, Nicolas Kryukov, Gregory V. Caponigro, Giordano Barretina, Jordi Venkatesan, Kavitha Margolin, Adam A. Wilson, Christopher J. Lehar, Joseph Jones, Michael D. Palescandolo, Emanuele Sougnez, Carrie Onofrio, Robert C. MacConaill, Laura Ardlie, Kristin Golub, Todd R. Morrissey, Michael Selers, William R. Schlegel, Robert Garraway, Levi A. TI Integrative analysis of the Cancer Cell Line Encyclopedia reveals genetic and transcriptional predictors of compound sensitivity SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Stransky, Nicolas; Kryukov, Gregory V.; Margolin, Adam A.; Sougnez, Carrie; Onofrio, Robert C.; Ardlie, Kristin; Golub, Todd R.; Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Caponigro, Giordano; Barretina, Jordi; Venkatesan, Kavitha; Wilson, Christopher J.; Lehar, Joseph; Jones, Michael D.; Morrissey, Michael; Selers, William R.; Schlegel, Robert] Novartis, Cambridge, MA USA. [Palescandolo, Emanuele; MacConaill, Laura] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5114 DI 10.1158/1538-7445.AM2012-5114 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606194 ER PT J AU Straussman, R Morikawa, T Shee, K Barzily-Ronki, M Du, JY Davis, A Gould, J Flaherty, KT Ogino, S Wargo, JA Golub, TR AF Straussman, Ravid Morikawa, Teppei Shee, Kevin Barzily-Ronki, Michal Du, Jinyan Davis, Ashli Gould, Joshua Flaherty, Keith T. Ogino, Shuji Wargo, Jennifer A. Golub, Todd R. TI Tumor microenvironment contributes to RAF-inhibitor resistance through HGF secretion SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Straussman, Ravid; Shee, Kevin; Barzily-Ronki, Michal; Du, Jinyan; Davis, Ashli; Gould, Joshua; Golub, Todd R.] Broad Inst, Cambridge, MA USA. [Morikawa, Teppei; Ogino, Shuji] Dana Farber Canc Inst, Boston, MA 02115 USA. [Flaherty, Keith T.; Wargo, Jennifer A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4837 DI 10.1158/1538-7445.AM2012-4837 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602328 ER PT J AU Tai, YT Chang, B Kong, SY Fulciniti, M Yang, G Calle, Y Hu, Y Lin, J Zhao, JJ Cagnetta, A Cea, M Sellitto, M Chen, M Carrasco, DR Elias, L Buggy, J Treon, SP Hunter, Z Matsui, W Richardson, P Munshi, NC Anderson, KC AF Tai, Yu-Tzu Chang, Betty Kong, Sun-Young Fulciniti, Mariateresa Yang, Guang Calle, Yolanda Hu, Yiguo Lin, Jianhong Zhao, Jian-Jun Cagnetta, Antonia Cea, Michele Sellitto, Michael Chen, Michelle Carrasco, Daniel R. Elias, Laurence Buggy, Joseph Treon, Steven P. Hunter, Zachary Matsui, William Richardson, Paul Munshi, Nikhil C. Anderson, Kenneth C. TI Targeting Bruton's tyrosine kinase with PCI-32765 blocks growth and survival of multiple myeloma and Waldenstrom macroglobulinemia via potent inhibition of osteoclastogenesis, cytokines/chemokine secretion, and myeloma stem-like cells in the bone marrow microenvironment SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Tai, Yu-Tzu; Kong, Sun-Young; Fulciniti, Mariateresa; Hu, Yiguo; Lin, Jianhong; Cagnetta, Antonia; Cea, Michele; Sellitto, Michael; Chen, Michelle; Richardson, Paul; Munshi, Nikhil C.; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Chang, Betty; Elias, Laurence; Buggy, Joseph] Pharmacyclics Inc, Sunnyvale, CA USA. [Yang, Guang; Treon, Steven P.; Hunter, Zachary] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Calle, Yolanda] Kings Coll London, Dept Haematol Med, London, England. [Zhao, Jian-Jun; Carrasco, Daniel R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Matsui, William] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Hematol Malignancies, Baltimore, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2934 DI 10.1158/1538-7445.AM2012-2934 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701602340 ER PT J AU Taplin, ME Chu, F Morrison, JP Pili, R Rettig, MB Stephenson, J Vogelzang, NJ Montgomery, RB AF Taplin, Mary-Ellen Chu, Franklin Morrison, Jodie P. Pili, Roberto Rettig, Matthew B. Stephenson, Joe Vogelzang, Nicholas J. Montgomery, R. Bruce TI ARMOR1: Safety of galeterone (TOK-001) in a Phase 1 clinical trial in chemotherapy naive patients with castration resistant prostate cancer (CRPC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Taplin, Mary-Ellen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chu, Franklin] San Bernardino Urol Associates, San Bernardino, CA USA. [Morrison, Jodie P.] Tokai Pharmaceut, Cambridge, MA USA. [Pili, Roberto] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Rettig, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Stephenson, Joe] Canc Ctr Carolinas, Greenville, SC USA. [Vogelzang, Nicholas J.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [Vogelzang, Nicholas J.] US Oncol Res, Las Vegas, NV USA. [Montgomery, R. Bruce] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 6 Z9 6 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA CT-07 DI 10.1158/1538-7445.AM2012-CT-07 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601406 ER PT J AU Tavera, LE Westerling, T Brown, M AF Tavera, Luz E. Westerling, Thomas Brown, Myles TI Genome-wide analysis of the vitamin D receptor (VDR) binding sites reveals vitamin D role mediating autophagy in luminal-like breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Tavera, Luz E.; Westerling, Thomas; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-275 DI 10.1158/1538-7445.AM2012-LB-275 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501260 ER PT J AU Ter-Minassian, M Chan, JA Hooshmand, SM Brais, LK Daskalova, A Heafield, R Qian, ZR Lin, XH Christiani, DC Kulke, MH AF Ter-Minassian, Monica Chan, Jennifer A. Hooshmand, Susanne M. Brais, Lauren K. Daskalova, Anastassia Heafield, Rachel Qian, Zhiron Lin, Xihong Christiani, David C. Kulke, Matthew H. TI Prognostic value of chromogranin A and alkaline phosphatase in patients with advanced neuroendocrine tumor SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ter-Minassian, Monica; Chan, Jennifer A.; Hooshmand, Susanne M.; Brais, Lauren K.; Daskalova, Anastassia; Heafield, Rachel; Qian, Zhiron; Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lin, Xihong; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3633 DI 10.1158/1538-7445.AM2012-3633 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601098 ER PT J AU Tobi, M Yang, YX Kaplan, D Gupta, R Rambus, M Naumoff, J Leavell, B Patel, P Sochacki, P Hatfield, J Lawson, J AF Tobi, Martin Yang, Yu-Xiao Kaplan, David Gupta, Rasna Rambus, MaryAnn Naumoff, Joanne Leavell, Bonita Patel, Pragnesh Sochacki, Paula Hatfield, James Lawson, James TI A non-invasive test for right-sided colonic neoplasia in diabetics at increased risk, independent of drug therapy and demographics SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Tobi, Martin; Yang, Yu-Xiao; Kaplan, David; Lawson, James] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Gupta, Rasna; Rambus, MaryAnn; Naumoff, Joanne; Leavell, Bonita; Patel, Pragnesh; Sochacki, Paula; Hatfield, James] Detroit VA Med Ctr, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4519 DI 10.1158/1538-7445.AM2012-4519 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601008 ER PT J AU Tye, K Luo, XX Westly, E Klein, RJ Kline, J Cohen, KS AF Tye, Karen Luo, Xixi Westly, Elizabeth Klein, Rachael J. Kline, Justin Cohen, Kenneth S. TI Host ephrinB2 regulates T-cells in tumor microenvironments SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Tye, Karen; Luo, Xixi; Westly, Elizabeth; Kline, Justin; Cohen, Kenneth S.] Univ Chicago, Res Ctr, Chicago, IL 60637 USA. [Klein, Rachael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 395 DI 10.1158/1538-7445.AM2012-395 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505448 ER PT J AU Ullal, AV Reiner, T Yang, KS Gorbatov, R Min, C Issadore, D Lee, H Weissleder, R AF Ullal, Adeeti V. Reiner, Thomas Yang, Katherine S. Gorbatov, Rostic Min, Changwook Issadore, David Lee, Hakho Weissleder, Ralph TI Nanoparticle mediated measurement of target-drug binding in cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ullal, Adeeti V.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Reiner, Thomas; Yang, Katherine S.; Gorbatov, Rostic; Min, Changwook; Issadore, David; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1968 DI 10.1158/1538-7445.AM2011-1968 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701600076 ER PT J AU Vaid, M Prasad, R Singh, T Sun, Q Katiyar, SK AF Vaid, Mudit Prasad, Ram Singh, Tripti Sun, Qian Katiyar, Santosh K. TI Grape seed proanthocyanidins inhibit UV-induced tolerogenic T-cell response through DNA repair-dependent functional activation of Langerhans cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Vaid, Mudit; Prasad, Ram; Singh, Tripti; Sun, Qian; Katiyar, Santosh K.] Univ Alabama Birmingham, Birmingham, AL USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1599 DI 10.1158/1538-7445.AM2012-1599 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701503331 ER PT J AU Vathipadiekal, V Ozbun, L Lee, JW Vivas-Mejia, P Lopez-Berestein, G Sood, AK Mok, SC Birrer, MJ AF Vathipadiekal, Vinod Ozbun, Laurent Lee, Jeong-Won Vivas-Mejia, Pablo Lopez-Berestein, Gabriel Sood, Anil K. Mok, Samuel C. Birrer, Michael J. TI Gene expression profile of chemoresponse of microdissected papillary serous tumors of the ovary identifies POLH and REV3L as potential therapeutic targets SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Vathipadiekal, Vinod; Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ozbun, Laurent] NCI, Bethesda, MD 20892 USA. [Lee, Jeong-Won; Vivas-Mejia, Pablo; Lopez-Berestein, Gabriel; Sood, Anil K.; Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5057 DI 10.1158/1538-7445.AM2012-5057 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606259 ER PT J AU Vira, D Basak, SK Lai, C Fishbein, MC Batra, RK Wang, MB Srivatsan, ES AF Vira, Darshni Basak, Saroj K. Lai, Chi Fishbein, Michael C. Batra, Raj K. Wang, Marilene B. Srivatsan, Eri S. TI Immunohistochemical variations in the expression of cancer stem cell and macrophage markers in primary and recurrent oral squamous cell carcinomas SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Vira, Darshni; Basak, Saroj K.; Lai, Chi; Fishbein, Michael C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Batra, Raj K.; Wang, Marilene B.; Srivatsan, Eri S.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Healthcare Syst, Los Angeles, CA 90095 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5355 DI 10.1158/1538-7445.AM2012-5355 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504131 ER PT J AU Vorvis, C Poultsides, GA Norton, JA Iliopoulos, D AF Vorvis, Christina Poultsides, George A. Norton, Jeffrey A. Iliopoulos, Dimitrios TI Identification and molecular characterization of pancreatic tumor-initiating cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Vorvis, Christina; Iliopoulos, Dimitrios] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Poultsides, George A.; Norton, Jeffrey A.] Stanford Univ, Med Ctr, Dept Surg, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5335 DI 10.1158/1538-7445.AM2012-5335 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504110 ER PT J AU Walker, SR Cerchietti, LC Nicolais, MC Yuan, GC Melnick, A Frank, DA AF Walker, Sarah R. Cerchietti, Leandro C. Nicolais, Maria C. Yuan, Guo-Cheng Melnick, Ad Frank, David A. TI Identification of BCL6 targeted therapies for breast cancer through gene expression networks SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Walker, Sarah R.; Nicolais, Maria C.; Yuan, Guo-Cheng; Frank, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cerchietti, Leandro C.; Melnick, Ad] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 971 DI 10.1158/1538-7445.AM2012-971 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602317 ER PT J AU Wang, YY Favoino, E Yu, L Ferrone, CR Ferrone, S Wang, XH AF Wang, Yangyang Favoino, Elvira Yu, Ling Ferrone, Cristina R. Ferrone, Soldano Wang, Xinhui TI Heat shock protein (HSP) Grp94-targeted combinatorial immunotherapy for pancreatic cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wang, Yangyang; Yu, Ling; Ferrone, Soldano; Wang, Xinhui] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Favoino, Elvira] Univ Bari, Bari, Italy. [Ferrone, Cristina R.] Harvard Univ, Sch Med, Boston, MA USA. [Ferrone, Cristina R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4390 DI 10.1158/1538-7445.AM2012-4390 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701500348 ER PT J AU Weeraratne, SD Archer, T Pugh, TJ Hargreaves, D Yu, FR Kautzman, A Jones, DTW Jaeger, N Tamayo, P Mesirov, JP Pfister, SM Lichter, P Crabtree, G Meyerson, M Pomeroy, SL Cho, YJ AF Weeraratne, Shyamal D. Archer, Tenley Pugh, Trevor J. Hargreaves, Diana Yu, Furong Kautzman, Amanda Jones, David T. W. Jaeger, Natalie Tamayo, Pablo Mesirov, Jill P. Pfister, Stefan M. Lichter, Peter Crabtree, Gerald Meyerson, Matthew Pomeroy, Scott L. Cho, Yoon-Jae TI Mutually exclusive somatic mutations in WNT pathway medulloblastomas reveal a critical interaction between DDX3X and SMARCA4 SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Weeraratne, Shyamal D.; Archer, Tenley; Pomeroy, Scott L.] Childrens Hosp, Boston, MA 02115 USA. [Pugh, Trevor J.; Tamayo, Pablo; Mesirov, Jill P.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Hargreaves, Diana; Yu, Furong; Kautzman, Amanda; Crabtree, Gerald; Cho, Yoon-Jae] Stanford Univ, Stanford, CA 94305 USA. [Jones, David T. W.; Jaeger, Natalie; Pfister, Stefan M.; Lichter, Peter] DKFZ, Heidelberg, Germany. [Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1313 DI 10.1158/1538-7445.AM2012-1313 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502420 ER PT J AU Wei, W Mohapatra, G Birrer, MJ AF Wei, Wei Mohapatra, Gayatry Birrer, Michael J. TI The FGF18/FGFR4 amplicon: Novel therapeutic biomarkers for ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wei, Wei; Mohapatra, Gayatry; Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI WEI, WEI/0000-0002-2315-3558 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1072 DI 10.1158/1538-7445.AM2012-1072 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701605437 ER PT J AU Weinstein, D Rambus, M Levi, E Yuan, MJ Lawson, MJ Tobi, M AF Weinstein, Douglas Rambus, MaryAnn Levi, Edi Yuan, Mei J. Lawson, Michael J. Tobi, Martin TI Adnab-9: A prospective stool biomarker for pancreatic ductal adenocarcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Weinstein, Douglas; Tobi, Martin] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Rambus, MaryAnn; Levi, Edi] Detroit VA Med Ctr, Detroit, MI USA. [Yuan, Mei J.] People Liberat Army Hosp, Beijing, Peoples R China. [Lawson, Michael J.] Kaiser Permanente Med Grp, Sacramento, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3699 DI 10.1158/1538-7445.AM2012-3699 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601361 ER PT J AU Westerling, T Tayera-Mendoza, L Brown, M AF Westerling, Thomas Tayera-Mendoza, Luz Brown, Myles TI Identification of functional enhancer SNPs in breast cancer models though ChIP-sequencing screeningd SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Westerling, Thomas; Tayera-Mendoza, Luz; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-406 DI 10.1158/1538-7445.AM2012-LB-406 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701604489 ER PT J AU Wheeler, HE Gamazon, ER Njiaju, UO Wing, C Njoku, C Baldwin, RM Owzar, K Winer, E Hudis, C Shulman, LN Ratain, MJ Kroetz, DL Cox, NJ Dolan, ME AF Wheeler, Heather E. Gamazon, Eric R. Njiaju, Uchenna O. Wing, Claudia Njoku, Chidiamara Baldwin, R. Michael Owzar, Kouros Winer, Eric Hudis, Clifford Shulman, Lawrence N. Ratain, Mark J. Kroetz, Deanna L. Cox, Nancy J. Dolan, M. Eileen TI Integration of cell line and Cancer and Leukemia Group B 40101 clinical trial genome-wide association analyses implicates multiple loci in paclitaxel-induced peripheral neuropathy SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wheeler, Heather E.; Gamazon, Eric R.; Njiaju, Uchenna O.; Wing, Claudia; Njoku, Chidiamara; Ratain, Mark J.; Cox, Nancy J.; Dolan, M. Eileen] Univ Chicago, Chicago, IL 60637 USA. [Baldwin, R. Michael; Kroetz, Deanna L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Owzar, Kouros] Duke Univ, Durham, NC USA. [Winer, Eric; Shulman, Lawrence N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hudis, Clifford] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1881 DI 10.1158/1538-7445.AM2012-1881 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501066 ER PT J AU Wilson, MA Zhao, FM Letrero, R D'Andrea, K Rimm, D Kirkwood, J Kluger, H Lee, S Flaherty, K Nathanson, K AF Wilson, Melissa Ann Zhao, Fengmin Letrero, Richard D'Andrea, Kurt Rimm, David Kirkwood, John Kluger, Harriet Lee, Sandra Flaherty, Keith Nathanson, Katherine TI Mutation analysis of melanoma tumor samples from ECOG 2603 clinical trial SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wilson, Melissa Ann; Letrero, Richard; D'Andrea, Kurt; Nathanson, Katherine] Univ Penn, Philadelphia, PA 19104 USA. [Zhao, Fengmin; Lee, Sandra] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rimm, David; Kluger, Harriet] Yale Univ, New Haven, CT USA. [Kirkwood, John] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Flaherty, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5557 DI 10.1158/1538-7445.AM2012-5557 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701601068 ER PT J AU Wirth, GJ Fendt, SM Bell, EL Keibler, MA Stephanopoulos, G Olumi, AF AF Wirth, Gregory J. Fendt, Sarah-Maria Bell, Eric L. Keibler, Mark A. Stephanopoulos, Gregory Olumi, Aria F. TI Metformin shifts prostate cancer metabolism towards a less malignant phenotype SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wirth, Gregory J.; Olumi, Aria F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fendt, Sarah-Maria; Bell, Eric L.; Keibler, Mark A.; Stephanopoulos, Gregory] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3234 DI 10.1158/1538-7445.AM2012-3234 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502290 ER PT J AU Wolf, J LoRusso, PM Camidge, RD Perez, JM Tabernero, J Hidalgo, M Schuler, M Tian, GG Soria, JC Delord, JP Campone, M Bachelot, T van der Noll, R Ringeisen, FP Nogova, L Sequist, LV Schellens, JHM AF Wolf, Jurgen LoRusso, Patricia M. Camidge, Ross D. Manuel Perez, Jose Tabernero, Josep Hidalgo, Manuel Schuler, Martin Tian, Gary G. Soria, Jean Charles Delord, Jean Pierre Campone, Mario Bachelot, Thomas van der Noll, Ruud Ringeisen, Francois P. Nogova, Lucia Sequist, Lecia V. Schellens, Jan H. M. TI A phase I dose escalation study of NVP-BGJ398, a selective pan FGFR inhibitor in genetically preselected advanced solid tumors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wolf, Jurgen; Nogova, Lucia] Uniklinikum Koln, Cologne, Germany. [LoRusso, Patricia M.] Karmanos Canc Inst, Detroit, MI USA. [Camidge, Ross D.] Univ Colorado, Aurora, CO USA. [Manuel Perez, Jose; Tabernero, Josep] Vall DHebron Hosp, Barcelona, Spain. [Hidalgo, Manuel] Hosp Univ Madrid, Madrid, Spain. [Schuler, Martin] Univ Duisburg Essen, West German Canc Ctr, Essen, Germany. [Tian, Gary G.] West Clin, Memphis, TN USA. [Soria, Jean Charles] Inst Gustave Roussy, Villejuif, France. [Delord, Jean Pierre] Claudius Regaud Inst, Toulouse, France. [Campone, Mario] Ctr Rene Gauducheau, F-44035 Nantes, France. [Bachelot, Thomas] Ctr Leon Berard, F-69373 Lyon, France. [van der Noll, Ruud; Schellens, Jan H. M.] Netherlands Canc Inst, Amsterdam, Netherlands. [Ringeisen, Francois P.] Novartis, Basel, Switzerland. [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-122 DI 10.1158/1538-7445.AM2012-LB-122 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701601397 ER PT J AU Wu, J Keng, V Patmore, DM Jousma, E Eaves, DW Johansson, G Schwartz, EB Fuchs, JR Dunn, S Lindquist, D Dombi, E Widemann, BC Stemmer-Rachamimov, AO Cancelas, JA Cripe, TP Largaespada, DA Ratner, N AF Wu, Jiangiang Keng, Vincent Patmore, Deanna M. Jousma, Edwin Eaves, David W. Johansson, Gunnar Schwartz, Eric B. Fuchs, James R. Dunn, Scott Lindquist, Diana Dombi, Eva Widemann, Brigitte C. Stemmer-Rachamimov, Anat O. Cancelas, Jose A. Cripe, Timothy P. Largaespada, David A. Ratner, Nancy TI An EGFR-STAT3 pathway promotes NF1 peripheral nerve tumorigenesis and transformation SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wu, Jiangiang; Patmore, Deanna M.; Jousma, Edwin; Eaves, David W.; Johansson, Gunnar; Dunn, Scott; Lindquist, Diana; Cancelas, Jose A.; Cripe, Timothy P.; Ratner, Nancy] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Keng, Vincent; Largaespada, David A.] Univ Minnesota, Minneapolis, MN USA. [Schwartz, Eric B.; Fuchs, James R.] Ohio State Univ, Columbus, OH 43210 USA. [Dombi, Eva; Widemann, Brigitte C.] NCI, Bethesda, MD 20892 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2937 DI 10.1158/1538-7445.AM2012-2937 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602343 ER PT J AU Yamada, S Fujii, T Fuchs, BC Sugimoto, H Nomoto, S Takeda, S Kodera, Y Nakao, A AF Yamada, Suguru Fujii, Tsutomu Fuchs, Bryan C. Sugimoto, Hiroyuki Nomoto, Shuji Takeda, Shin Kodera, Yasuhiro Nakao, Akimasa TI Implication of epithelial to mesenchymal transition (EMT) in pancreatic cancer prognosis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Nomoto, Shuji; Takeda, Shin; Kodera, Yasuhiro] Nagoya Univ, Grad Sch Med, Nagoya, Aichi 4648601, Japan. [Fuchs, Bryan C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nakao, Akimasa] Nagoya Cent Hosp, Nagoya, Aichi, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 458 DI 10.1158/1538-7445.AM2012-458 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701506075 ER PT J AU Yamada, S Fujii, T Wei, L Hoshida, Y Lauwers, GY Schmitt, AD Lanuti, M Tanabe, KK Fuchs, BC AF Yamada, Suguru Fujii, Tsutomu Wei, Lan Hoshida, Yujin Lauwers, Gregory Y. Schmitt, Anthony D. Lanuti, Michael Tanabe, Kenneth K. Fuchs, Bryan C. TI EGCG prevents hepatocellular carcinoma development in a diethylnitrosamine-induced rat model SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yamada, Suguru; Fujii, Tsutomu; Wei, Lan; Lauwers, Gregory Y.; Schmitt, Anthony D.; Lanuti, Michael; Tanabe, Kenneth K.; Fuchs, Bryan C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoshida, Yujin] Broad Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5427 DI 10.1158/1538-7445.AM2012-5427 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701503422 ER PT J AU Yamamura, S Sharanjot, S Shahana, M Hirata, H Ueno, K Chang, I Chiyomaru, T Tanaka, Y Dahiya, R AF Yamamura, Soichiro Sharanjot, Saini Shahana, Majid Hirata, Hiroshi Ueno, Koji Chang, Inik Chiyomaru, Takeshi Tanaka, Yuichiro Dahiya, Rajvir TI MicroRNA-141 inhibits proliferation and invasion by suppressing the Wnt signaling pathway in renal cell carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yamamura, Soichiro; Sharanjot, Saini; Shahana, Majid; Hirata, Hiroshi; Ueno, Koji; Chang, Inik; Chiyomaru, Takeshi; Tanaka, Yuichiro; Dahiya, Rajvir] San Francisco VA Med Ctr, San Francisco, CA USA. [Yamamura, Soichiro; Sharanjot, Saini; Shahana, Majid; Hirata, Hiroshi; Ueno, Koji; Chang, Inik; Chiyomaru, Takeshi; Tanaka, Yuichiro; Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 3149 DI 10.1158/1538-7445.AM2012-3149 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701503100 ER PT J AU Yang, JJ Gameiro, PA Stephanopoulos, G Iliopoulos, O AF Yang, Juanjuan Gameiro, Paulo A. Stephanopoulos, Gregory Iliopoulos, Othon TI Regulation of the glutamine-to-lipid pathway by HIF: Reductive TCA cycle is a metabolic signature of VHL deficiency SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yang, Juanjuan; Gameiro, Paulo A.; Iliopoulos, Othon] Massachusetts Gen Hosp, Navy Yard, MA USA. [Stephanopoulos, Gregory] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1132 DI 10.1158/1538-7445.AM2012-1132 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701606040 ER PT J AU Yang, K Thurber, G Reiner, T Kohler, R Weissleder, R AF Yang, Katherine Thurber, Greg Reiner, Thomas Kohler, Rainer Weissleder, Ralph TI In vivo imaging and tracking of a PARP inhibitor at single-cell resolution SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yang, Katherine; Thurber, Greg; Reiner, Thomas; Kohler, Rainer; Weissleder, Ralph] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4293 DI 10.1158/1538-7445.AM2012-4293 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505430 ER PT J AU Yen, K Wang, F Choe, S Schalm, S Hansen, E Straley, K Popovici-Muller, J Travins, J Yang, H Silverman, L Kaelin, W Gross, S Dang, L Salituro, F Saunders, J Schenkein, D Su, M Biller, S AF Yen, Kate Wang, Fang Choe, Sung Schalm, Stefanie Hansen, Erica Straley, Kimberly Popovici-Muller, Janeta Travins, Jeremy Yang, Hua Silverman, Lee Kaelin, William Gross, Stefan Dang, Lenny Salituro, Frank Saunders, Jeff Schenkein, David Su, Michael Biller, Scott TI IDH mutations and tumorgenicity SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yen, Kate; Wang, Fang; Choe, Sung; Schalm, Stefanie; Hansen, Erica; Straley, Kimberly; Popovici-Muller, Janeta; Travins, Jeremy; Yang, Hua; Silverman, Lee; Gross, Stefan; Dang, Lenny; Salituro, Frank; Saunders, Jeff; Schenkein, David; Su, Michael; Biller, Scott] Agios Pharmaceut, Cambridge, MA USA. [Kaelin, William] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-164 DI 10.1158/1538-7445.AM2012-LB-164 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501293 ER PT J AU Yeung, TL Leung, C Ghosh, S Liu, JS Wong, KK Birrer, MJ Mok, SC AF Yeung, Tsz-Lun Leung, Cecilia Ghosh, Sue Liu, Jinsong Wong, Kwong-Kwok Birrer, Michael J. Mok, Samuel C. TI TGF-beta induced stromal versican promotes cancer invasion in advanced stage serous ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yeung, Tsz-Lun; Leung, Cecilia; Wong, Kwong-Kwok; Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Ghosh, Sue] Brigham & Womens Hosp, Gynecol & Reprod Biol, Boston, MA 02115 USA. [Liu, Jinsong] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1507 DI 10.1158/1538-7445.AM2012-1507 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502183 ER PT J AU Yigit, M Ghosh, S Medarova, Z Moore, AV AF Yigit, Mehmet Ghosh, Subrata Medarova, Zdravka Moore, Anna V. TI Image-guided miRNA therapy for metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yigit, Mehmet; Ghosh, Subrata; Medarova, Zdravka; Moore, Anna V.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2952 DI 10.1158/1538-7445.AM2012-2952 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501163 ER PT J AU Yonesaka, K Okamoto, I Taroh, S Zejnullahu, K Nishio, K Fukuoka, M Janne, PA Nakagawa, K AF Yonesaka, Kimio Okamoto, Isamu Taroh, Satoh Zejnullahu, Kreshnik Nishio, Kazuto Fukuoka, Masahiro Janne, Pasi A. Nakagawa, Kazuhiko TI Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutics antibody cetuximab SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yonesaka, Kimio; Okamoto, Isamu; Nishio, Kazuto; Nakagawa, Kazuhiko] Kinki Univ, Sch Med, Osaka 589, Japan. [Taroh, Satoh] Osaka Univ, Sch Med, Osaka, Japan. [Zejnullahu, Kreshnik; Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fukuoka, Masahiro] Izumi Municipal Hosp, Osaka, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4833 DI 10.1158/1538-7445.AM2012-4833 PG 1 WC Oncology SC Oncology GA V43SR UT WOS:000209701602324 ER PT J AU Young, CD Kuba, MG Owens, P Balko, JM Pfefferle, A Sanchez, V Perou, CM Zhao, JJ Cook, RS Arteaga, CL AF Young, Christian D. Kuba, Maria G. Owens, Philip Balko, Justin M. Pfefferle, Adam Sanchez, Violeta Perou, Charles M. Zhao, Jean J. Cook, Rebecca S. Arteaga, Carlos L. TI Conditional loss of ErbB3 delays mammary gland hyperplasias induced by mutant PIK3CA in transgenic mice, but does not affect mammary tumor latency, gene expression or signaling SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Young, Christian D.; Kuba, Maria G.; Owens, Philip; Balko, Justin M.; Sanchez, Violeta; Cook, Rebecca S.; Arteaga, Carlos L.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Pfefferle, Adam; Perou, Charles M.] Univ N Carolina, Chapel Hill, NC USA. [Zhao, Jean J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-103 DI 10.1158/1538-7445.AM2012-LB-103 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701506081 ER PT J AU Yu, M Ting, DT Stott, SL Wittner, BS Ozsolak, F Paul, S Ciciliano, JC Smas, ME Gilman, AJ Ulman, MJ Contino, G Alagesan, B Brannigan, BW Milos, PM Ryan, DP Seguist, LV Bardeesy, N Ramaswamy, S Toner, M Maheswaran, S Haber, DA AF Yu, Min Ting, David T. Stott, Shannon L. Wittner, Ben S. Ozsolak, Fatih Paul, Suchismita Ciciliano, Jordan C. Smas, Malgorzata E. Gilman, Anna J. Ulman, Matthew J. Contino, Gianmarco Alagesan, Brinda Brannigan, Brian W. Milos, Patrice M. Ryan, David P. Seguist, Lecia V. Bardeesy, Nabeel Ramaswamy, Sridhar Toner, Mehmet Maheswaran, Shyamala Haber, Daniel A. TI RNA sequencing of circulating tumor cells implicates WNT signaling in pancreatic cancer metastasis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yu, Min; Ting, David T.; Stott, Shannon L.; Wittner, Ben S.; Paul, Suchismita; Ciciliano, Jordan C.; Smas, Malgorzata E.; Gilman, Anna J.; Ulman, Matthew J.; Contino, Gianmarco; Alagesan, Brinda; Brannigan, Brian W.; Ryan, David P.; Seguist, Lecia V.; Bardeesy, Nabeel; Ramaswamy, Sridhar; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A.] Massachusetts Gen Hosp, Charlestown, MA USA. [Ozsolak, Fatih; Milos, Patrice M.] Helicos BioSci Corp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 5304 DI 10.1158/1538-7445.AM2012-5304 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701504077 ER PT J AU Yuan, JP Leblanc, P Kashiwagi, S Nezivar, J Righi, E Santosuosso, M Korochkina, S Orsulic, S Scholler, N Dranoff, G Gelfand, J Poznansky, M AF Yuan, Jianping Leblanc, Pierre Kashiwagi, Satoshi Nezivar, Jean Righi, Elda Santosuosso, Michael Korochkina, Svetlana Orsulic, Sandra Scholler, Nathalie Dranoff, Glenn Gelfand, Jeffrey Poznansky, Mark TI MTBhsp70 fusion protein targeting mesothelin augments tumor specific T cell responses and prolongs survival in a murine model of ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yuan, Jianping; Leblanc, Pierre; Kashiwagi, Satoshi; Nezivar, Jean; Righi, Elda; Santosuosso, Michael; Korochkina, Svetlana; Gelfand, Jeffrey; Poznansky, Mark] Massachusetts Gen Hosp, Charlestown, MA USA. [Orsulic, Sandra] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Scholler, Nathalie] Univ Penn, Philadelphia, PA 19104 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1578 DI 10.1158/1538-7445.AM2012-1578 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501019 ER PT J AU Zhang, XH Giovannucci, E Wu, K Gao, X Hu, F Ogino, S Schernhammer, E Fuchs, C Pollak, M Willett, W Ma, J AF Zhang, Xuehong Giovannucci, Edward Wu, Kana Gao, Xiang Hu, Frank Ogino, Shuji Schernhammer, Eva Fuchs, Charles Pollak, Michael Willett, Walter Ma, Jing TI Self-reported sleep duration and subsequent risk of colorectal cancer in two large cohorts of women and men SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Zhang, Xuehong; Giovannucci, Edward; Gao, Xiang; Hu, Frank; Schernhammer, Eva; Fuchs, Charles; Willett, Walter; Ma, Jing] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Zhang, Xuehong; Giovannucci, Edward; Gao, Xiang; Hu, Frank; Ogino, Shuji; Schernhammer, Eva; Fuchs, Charles; Willett, Walter; Ma, Jing] Harvard Univ, Sch Med, Boston, MA USA. [Giovannucci, Edward; Hu, Frank; Willett, Walter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Dept Nutr, Boston, MA 02115 USA. [Wu, Kana; Gao, Xiang] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji; Fuchs, Charles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pollak, Michael] McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Canc Prevent Res Unit,Dept Med, Montreal, PQ H3T 1E2, Canada. [Pollak, Michael] McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Canc Prevent Res Unit,Dept Oncol, Montreal, PQ H3T 1E2, Canada. [Pollak, Michael] McGill Univ, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA LB-323 DI 10.1158/1538-7445.AM2012-LB-323 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701603057 ER PT J AU Zhang, YX Remillard, SP Demetri, GD Wang, SM Debussche, L Wagner, AJ AF Zhang, Yixiang Remillard, Stephen P. Demetri, George D. Wang, Shaomeng Debussche, Laurent Wagner, Andrew J. TI Potent inhibition of human liposarcoma cell growth and survival by novel modulators of the MDM2-p53 interaction SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Zhang, Yixiang; Remillard, Stephen P.; Demetri, George D.; Wagner, Andrew J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wang, Shaomeng] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Debussche, Laurent] Sanofi Oncol Business Div, Vitry Sur Seine, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 2786 DI 10.1158/1538-7445.AM2012-2786 PG 2 WC Oncology SC Oncology GA V43SR UT WOS:000209701603266 ER PT J AU Zhou, AY Shen, RR Kim, E Chen, ZJ Hahn, WC AF Zhou, Alicia Y. Shen, Rhine R. Kim, Eejung Chen, Zhijian Hahn, William C. TI Ubiquitination of the breast cancer oncogene IKK alpha is essential for transformation SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Zhou, Alicia Y.; Shen, Rhine R.; Kim, Eejung; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Zhijian] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4863 DI 10.1158/1538-7445.AM2012-4863 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701501152 ER PT J AU Zhu, K Cron, K Hsieh, G Merzon, D Evans, D Ng, K Chen, CC D'Andrea, AD Kozono, D AF Zhu, Kaya Cron, Kyle Hsieh, Grace Merzon, Dmitry Evans, Daniel Ng, Kimberly Chen, Clark C. D'Andrea, Alan D. Kozono, David TI Whole genome RNAi screen identifies proteasome inhibition as a strategy for NSCLC radiosensitization SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Zhu, Kaya; Cron, Kyle; Hsieh, Grace; Merzon, Dmitry; Evans, Daniel; Ng, Kimberly; D'Andrea, Alan D.; Kozono, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Clark C.] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 1448 DI 10.1158/1538-7445.AM2012-1448 PG 2 WC Oncology SC Oncology GA V43SQ UT WOS:000209701502058 ER PT J AU Zhu, SZ Lee, JS Guo, F Shin, JM Perez-Atayde, AR Kutok, JL Rodig, SJ Neuberg, DS Helman, D Feng, H Stewart, RA Wang, WC George, RE Kanki, J Look, AT AF Zhu, Shizhen Lee, Jeong-Soo Guo, Feng Shin, Jimann Perez-Atayde, Antonio R. Kutok, Jeffery L. Rodig, Scott J. Neuberg, Donna S. Helman, Daniel Feng, Hui Stewart, Rodney A. Wang, Wenchao George, Rani E. Kanki, John Look, A. Thomas TI Activated ALK collaborates with MYCN in neuroblastoma pathogenesis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Zhu, Shizhen; Lee, Jeong-Soo; Guo, Feng; Shin, Jimann; Neuberg, Donna S.; Helman, Daniel; Feng, Hui; Wang, Wenchao; George, Rani E.; Kanki, John; Look, A. Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Perez-Atayde, Antonio R.] Childrens Hosp Boston, Boston, MA USA. [Kutok, Jeffery L.] Infin Pharmaceut, Cambridge, MA USA. [Rodig, Scott J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Stewart, Rodney A.] Huntsman Canc Inst, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2012 VL 72 SU 8 MA 4252 DI 10.1158/1538-7445.AM2012-4252 PG 1 WC Oncology SC Oncology GA V43SQ UT WOS:000209701505163 ER EF