FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Schauer, IE Knaub, LA Lloyd, M Watson, PA Gliwa, C Lewis, KE Chait, A Klemm, DJ Gunter, JM Bouchard, R McDonald, TO O'Brien, KD Reusch, JEB AF Schauer, Irene E. Knaub, Leslie A. Lloyd, Monique Watson, Peter A. Gliwa, Catherine Lewis, Katherine E. Chait, Alan Klemm, Dwight J. Gunter, Jody M. Bouchard, Ron McDonald, Thomas O. O'Brien, Kevin D. Reusch, Jane E. B. TI CREB Downregulation in Vascular Disease A Common Response to Cardiovascular Risk SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; insulin resistance; CREB; LDL; vascular smooth muscle ID ELEMENT-BINDING-PROTEIN; MUSCLE-CELL-PROLIFERATION; SERUM AMYLOID-A; GROWTH-FACTOR-I; TRANSCRIPTION FACTOR; GENE-EXPRESSION; MESSENGER-RNA; PHOSPHATIDYLINOSITOL 3-KINASE; DILATED CARDIOMYOPATHY; NEUROBLASTOMA-CELLS AB Objective-To examine the impact of low-density lipoprotein (LDL), an established mediator of atherosclerosis, on the transcription factor cAMP-response element-binding protein (CREB), which is a regulator of vascular smooth muscle cell (VSMC) quiescence. Methods and Results-VSMC CREB content is diminished in rodent models of diabetes and pulmonary hypertension. We examined aortic CREB content in rodent models of aging, hypertension, and insulin resistance, and we determined nuclear CREB protein in the medial VSMC of high-fat-fed LDL receptor-null mice. There was significant loss of CREB protein in all models. In vitro, primary culture rat aortic VSMC exposed to LDL and oxidized LDL exhibited a rapid, transient increase in CREB phosphorylation and transient phosphorylation/activation of Akt, ERK, JNK, ans p38 MAPK. Exposure to oxidized LDL, but not to LDL, for 24 to 48 hours decreased CREB protein in a dose-dependent fashion and led to nuclear exclusion of CREB. Pharmacological reactive oxygen species scavengers and inhibition of ERK activation blocked oxidized LDL-mediated CREB downregulation. Conclusion-These data support a model wherein loss of VSMC CREB protein, which renders these cells more susceptible to activation and apoptosis, is a common pathological response to vascular injury and potentially contributes to plaque progression. (Arterioscler Thromb Vasc Biol. 2010; 30: 733-741.) C1 [Schauer, Irene E.; Knaub, Leslie A.; Watson, Peter A.; Gliwa, Catherine; Gunter, Jody M.; Bouchard, Ron; Reusch, Jane E. B.] Denver VA Med Ctr, Denver, CO 80220 USA. [Schauer, Irene E.; Knaub, Leslie A.; Lloyd, Monique; Watson, Peter A.; Gunter, Jody M.; Reusch, Jane E. B.] Univ Colorado, Dept Med, Div Endocrinol Diabet & Metab, Aurora, CO USA. [Klemm, Dwight J.] Univ Colorado, Dept Med, Div Cardiovasc Pulm Res, Aurora, CO USA. [Lewis, Katherine E.] ZymoGenetics Inc, Seattle, WA USA. [McDonald, Thomas O.; O'Brien, Kevin D.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA. [Lewis, Katherine E.; Chait, Alan] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Reusch, JEB (reprint author), Denver VA Med Ctr, ENDO 111-H,Room 9C120B,1055 Clermont St, Denver, CO 80220 USA. EM jane.reusch@ucdenver.edu FU VA Merit; Merck Investigator-initiated research support; BIRCWH K12; [DK64741]; [HL56481]; [P30 DK035816] FX VA Merit (to J.E.B.R.) and DK64741 (to J.E.B.R.), HL56481 (to D.J.K.), Merck Investigator-initiated research support (to J.E.B.R., K.D.O.), P30 DK035816 (to A.C., T.O.M.,K.D.O.), and BIRCWH K12 (to I. E. S.). NR 56 TC 40 Z9 40 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2010 VL 30 IS 4 BP 733 EP U213 DI 10.1161/ATVBAHA.109.199133 PG 21 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 570XR UT WOS:000275712500017 PM 20150559 ER PT J AU Rosenzweig, HL Jann, MJ Vance, EE Planck, SR Rosenbaum, JT Davey, MP AF Rosenzweig, Holly L. Jann, Monica J. Vance, Emily E. Planck, Stephen R. Rosenbaum, James T. Davey, Michael P. TI Nucleotide-Binding Oligomerization Domain 2 and Toll-like Receptor 2 Function Independently in a Murine Model of Arthritis Triggered by Intraarticular Peptidoglycan SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NOD-LIKE RECEPTORS; MURAMYL DIPEPTIDE; RHEUMATOID-ARTHRITIS; DENDRITIC CELLS; ACTIVATION; AGONISTS; RESPONSES; INNATE; INFLAMMATION; RECOGNITION AB Objective. Blau syndrome is an autoinflammatory disease resulting from mutations in the NOD2 gene, wherein granulomatous arthritis, uveitis, and dermatitis develop. The mechanisms by which aberrant NOD2 causes joint inflammation are poorly understood. Indeed, very few studies have addressed the function of nucleotide-binding oligomerization domain 2 (NOD-2) in the joint. This study was undertaken to investigate NOD-2 function in an experimental model of arthritis and to explore the potential interplay between Toll-like receptor 2 (TLR-2) and NOD-2 in joint inflammation. Methods. Mice deficient in TLR-2, myeloid differentiation factor 88 (MyD88), or NOD-2 and their wildtype controls were given an intraarticular injection of muramyl dipeptide (MDP), peptidoglycan (PG; a metabolite of which is MDP), or palmitoyl-3-cysteine-serine-lysine-4 (Pam(3)CSK(4)), a synthetic TLR-2 agonist. Joint inflammation was assessed by near-infrared fluorescence imaging and histologic analysis. Results. Locally administered PG resulted in joint inflammation, which was markedly reduced in mice deficient in either TLR-2 or the TLR signaling mediator MyD88. In addition to TLR-2 signaling events, NOD-2 mediated joint inflammation, as evidenced by the fact that mice deficient in NOD-2 showed significantly reduced PG-induced arthritis. TLR-2 or MyD88 deficiency did not influence arthritis induced by the specific NOD-2 agonist MDP. In addition, NOD-2 deficiency did not alter the TLR-2-dependent joint inflammation elicited by the synthetic TLR-2 agonist Pam(3)CSK(4). Conclusion. Whereas NOD-2 and TLR-2 are both critical for the development of PG-induced arthritis, they appear to elicit inflammation independently of each other. Our findings indicate that NOD-2 plays an inflammatory role in arthritis. C1 [Rosenzweig, Holly L.; Vance, Emily E.; Planck, Stephen R.; Rosenbaum, James T.; Davey, Michael P.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Jann, Monica J.; Davey, Michael P.] Portland VA Med Ctr, Portland, OR USA. RP Rosenzweig, HL (reprint author), Oregon Hlth & Sci Univ, Mail Stop L467 AD,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM rosenzwh@ohsu.edu FU Stan and Madelle Rosenfeld Family Trust; Fund for Arthritis and Infectious Disease Research; NIH (National Eye Institute) [F32-EY-017254, EY-013093]; Research to Prevent Blindness Foundation; American College of Rheumatology Research and Education Foundation; Oregon Health & Science University; VA Merit Review FX Supported by the Stan and Madelle Rosenfeld Family Trust and the Fund for Arthritis and Infectious Disease Research. Dr. Rosenzweig's work was supported by the NIH (National Eye Institute grant F32-EY-017254) and the Research to Prevent Blindness Foundation; she is recipient of an American College of Rheumatology Research and Education Foundation New Investigator award and co-recipient of a Gerlinger award through the Oregon Health & Science University. Dr. Rosenbaum's work was supported by the NIH (National Eye Institute grant EY-013093). Dr. Davey's work was supported by a VA Merit Review grant; he is co-recipient of a Gerlinger award through the Oregon Health & Science University. NR 31 TC 23 Z9 23 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD APR PY 2010 VL 62 IS 4 BP 1051 EP 1059 DI 10.1002/art.27335 PG 9 WC Rheumatology SC Rheumatology GA 619LS UT WOS:000279432300016 PM 20131263 ER PT J AU Milberg, WP McGlinchey, RE AF Milberg, William P. McGlinchey, Regina E. TI Comment on Shomstein, Kimchi, Hammer, and Behrmann (2010): A case study in methodological anosagnosia? SO ATTENTION PERCEPTION & PSYCHOPHYSICS LA English DT Editorial Material ID SPATIAL NEGLECT; ATTENTION AB Shomstein, Kimchi, Hammer, and Behrmann (2010) try to capitalize on the apparent dissociation between vision and the processes that seem to mediate neglect patients' attentional selection and awareness to investigate the processing of perceptual grouping in the absence of visual attention. We argue that to assess this type of dissociation requires specific methodological adaptations to determine whether visual attention is in operation. We caution that Shomstein et al.'s article does not present convincing evidence of grouping without attentional selection because they do not directly assess attentional selection in their experimental task. C1 [Milberg, William P.] VA Boston Healthcare Syst, GRECC 182, Boston, MA 02130 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Milberg, WP (reprint author), VA Boston Healthcare Syst, GRECC 182, 150 S Huntington Ave, Boston, MA 02130 USA. EM william_milberg@hms.harvard.edu RI McGlinchey, Regina/R-1971-2016 NR 13 TC 1 Z9 1 U1 0 U2 0 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 1943-3921 J9 ATTEN PERCEPT PSYCHO JI Atten. Percept. Psychophys. PD APR PY 2010 VL 72 IS 3 BP 619 EP 621 DI 10.3758/APP.72.3.619 PG 3 WC Psychology; Psychology, Experimental SC Psychology GA 653DI UT WOS:000282067000008 PM 20348568 ER PT J AU Gukovsky, I Gukovskaya, AS AF Gukovsky, Ilya Gukovskaya, Anna S. TI Impaired autophagy underlies key pathological responses of acute pancreatitis SO AUTOPHAGY LA English DT Editorial Material DE pancreatitis; pancreatic acinar cell; trypsinogen activation; vacuole formation; autophagic flux; protein degradation; cathepsin processing AB The main function of the exocrine pancreas is to produce digestive enzymes, which normally are secreted as inactive zymogens and become activated after reaching the duodenum. Pancreatitis is a relatively common and potentially fatal inflammatory disease of the exocrine pancreas. Its mild forms are self-limited, but severe pancreatitis has 10%-30% mortality. The pathogenesis of pancreatitis remains obscure, and there are no specific treatments. The disease is believed to initiate in acinar cells, the main cell type of the exocrine pancreas. Hallmark responses of acute pancreatitis are the premature, intra-acinar cell activation of trypsinogen (i.e., its conversion from zymogen to active trypsin), vacuole accumulation, inflammation and death of acinar cells through both necrosis and apoptosis. C1 [Gukovsky, Ilya] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Gukovsky, I (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM igukovsk@ucla.edu FU NIAAA NIH HHS [P50 AA011999]; NIDDK NIH HHS [R01 DK059936] NR 0 TC 19 Z9 24 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD APR 1 PY 2010 VL 6 IS 3 BP 428 EP 429 PG 2 WC Cell Biology SC Cell Biology GA 577CJ UT WOS:000276198200020 PM 20215882 ER PT J AU Genevay, S Atlas, SJ AF Genevay, Stephane Atlas, Steven J. TI Lumbar Spinal Stenosis SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY LA English DT Article DE lumbar spinal stenosis; neurogenic claudication; foraminal stenosis; radicular pain ID LOW-BACK-PAIN; CLINICAL-PRACTICE GUIDELINE; RANDOMIZED CONTROLLED-TRIAL; EPIDURAL STEROID INJECTION; PORCINE CAUDA-EQUINA; QUALITY-OF-LIFE; DOUBLE-BLIND; INTERMITTENT CLAUDICATION; CANAL STENOSIS; RADICULAR PAIN AB Lumbar spinal stenosis (LSS) is most commonly due to degenerative changes in older individuals. LSS is being more commonly diagnosed and may relate to better access to advanced imaging and to an ageing population. This review focusses on radicular symptoms related to degenerative central and lateral stenosis and updates knowledge of LSS pathophysiology, diagnosis and management. Since patients with anatomic LSS can range from asymptomatic to severely disabled, the clinical diagnosis focusses on symptoms and examination findings associated with LSS. Imaging findings are helpful for patients with persistent, bothersome symptoms in whom invasive treatments are being considered. There is limited information from high-quality studies about the relative merits and demerits of commonly used treatments. Interpreting and comparing results of available research are limited by a lack of consensus about the definition of LSS. Nevertheless, evidence supports decompressive laminectomy for patients with persistent and bothersome symptoms. Recommendations favour a shared decision-making approach clue to important trade-offs between alternative therapies and differences among patients in their preferences and values. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Atlas, Steven J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Genevay, Stephane] Univ Hosp Geneva, Div Rheumatol, Geneva, Switzerland. RP Atlas, SJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM stephane.genevay@hcuge.ch; satlas@partners.org OI Genevay, Stephane/0000-0003-4752-3186 FU NIAMS NIH HHS [P60 AR048094, P60 AR048094-01A10003] NR 92 TC 69 Z9 81 U1 1 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6942 J9 BEST PRACT RES CL RH JI Best Pract. Res. Clin. Rheumatol. PD APR PY 2010 VL 24 IS 2 BP 253 EP 265 DI 10.1016/j.berh.2009.11.001 PG 13 WC Rheumatology SC Rheumatology GA 583ME UT WOS:000276679600010 PM 20227646 ER PT J AU Novik, E Maguire, TJ Chao, PY Cheng, KC Yarmush, ML AF Novik, Eric Maguire, Timothy J. Chao, Piyun Cheng, K. C. Yarmush, Martin L. TI A microfluidic hepatic coculture platform for cell-based drug metabolism studies SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Microfluidics; Human hepatocyte; Coculture; Hepatic clearance; Metabolism ID HEPATOCYTE-SPECIFIC FUNCTIONS; SMALL-SCALE BIOREACTOR; LONG-TERM MAINTENANCE; FLAT-PLATE BIOREACTOR; OXYGEN-UPTAKE RATES; IN-VITRO DRUG; CULTURED-HEPATOCYTES; LIVER; MICROCHANNEL; PREDICTION AB Within the global pharmaceutical and biotech industries, there is significant interest in identifying in vitro screening systems that are more human-relevant-i.e., that offer greater utility in predicting subcellular and cellular physiological responses in humans in vivo-and that thereby allow investigators to reduce the incidence of costly late-stage failures during pharmaceutical clinical trials, as well as to reduce the use of animals in drug testing. Currently incumbent in vitro screening methods, such as culturing human hepatocytes in suspension, while useful, are limited by a lack of long term cellular function. In order to address this limitation, we have established an integrated, microfluidic, in vitro platform that combines the patented H mu RELII microdevice with a hepatic coculture system. In the present report, we use this platform to study clearance and metabolite generation of a battery of molecular entities. The results show that the flow-based coculture system is capable of clearing, with improved resolution and predictive value, compounds with high, medium, and low clearance values. In addition, when coculture is coupled with flow, higher metabolite production rates are obtained than in static systems. (C) 2009 Elsevier Inc. All rights reserved. C1 [Cheng, K. C.] Schering Plough Res Inst, Kenilworth, NJ 07033 USA. [Novik, Eric; Maguire, Timothy J.; Chao, Piyun] Hurel Corp, Beverly Hills, CA USA. [Yarmush, Martin L.] Boston Shriners Burns Hosp, Boston, MA USA. [Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn & Med, Boston, MA USA. RP Cheng, KC (reprint author), Schering Plough Res Inst, Kenilworth, NJ 07033 USA. EM kuo-chi.cheng@spcorp.com FU NIBIB NIH HHS [P41 EB002503-07, P41 EB002503] NR 41 TC 86 Z9 89 U1 1 U2 38 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 1 PY 2010 VL 79 IS 7 BP 1036 EP 1044 DI 10.1016/j.bcp.2009.11.010 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 557JQ UT WOS:000274665800012 PM 19925779 ER PT J AU Evans, KC AF Evans, Karleyton C. TI Cortico-limbic circuitry and the airways: Insights from functional neuroimaging of respiratory afferents and efferents SO BIOLOGICAL PSYCHOLOGY LA English DT Review DE Neuroimaging; fMRI; PET; Respiration; Breathing; Dyspnea; Motor control; Anxiety ID CENTRAL HYPOVENTILATION SYNDROME; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; OBSTRUCTIVE SLEEP-APNEA; FMRI SIGNAL CHANGES; EVENT-RELATED FMRI; OLD-WORLD MONKEY; AIR HUNGER; PANIC DISORDER; CARBON-DIOXIDE AB After nearly two decades of active research, functional neuroimaging has demonstrated utility in the identification of cortical, limbic, and paralimbic (cortico-limbic) brain regions involved in respiratory control and respiratory perception. Before the recent boon of human neuroimaging studies, the location of the principal components of respiratory-related cortico-limbic circuitry had been unknown and their function had been poorly understood. Emerging neuroimaging evidence in both healthy and patient populations suggests that cognitive and emotional/affective processing within cortico-limbic circuitry modulates respiratory control and respiratory perception. This paper will review functional neuroimaging studies of respiration with a focus on whole brain investigations of sensorimotor pathways that have identified respiratory-related neural circuitry known to overlap emotional/affective cortico-limbic circuitry. To aid the interpretation of present and future findings, the complexities and challenges underlying neuroimaging methodologies will also be reviewed as applied to the study of respiration physiology. (C) 2010 Elsevier B.V. All rights reserved. C1 [Evans, Karleyton C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Evans, Karleyton C.] Harvard Univ, Sch Med, Boston, MA USA. RP Evans, KC (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, Lab Neuroimaging Anxiety & Resp Psychophysiol, 13th St,Bldg 149,Suite 2625, Charlestown, MA 02129 USA. EM kcevans@partners.org FU NIMH [K23 MH086619]; NCCAM [R21 AT003425-01A2S1]; Massachusetts General Hospital FX This work was primarily supported by K23 MH086619 (NIMH). Within the last year Dr. Evans has received support from R21 AT003425-01A2S1 (NCCAM), an Investigator Initiated Research Agreement from Pfizer Ltd., and a Faculty Development Award from the Massachusetts General Hospital Executive Committee on Research. Tina Chou and Annette M. Schmid are acknowledged for their editorial assistance. Special thanks are expressed to Kenneth Townsend and Randy Edgington for their artistic contribution to Fig. 1. NR 143 TC 44 Z9 44 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD APR PY 2010 VL 84 IS 1 SI SI BP 13 EP 25 DI 10.1016/j.biopsycho.2010.02.005 PG 13 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 606YX UT WOS:000278466200003 PM 20211221 ER PT J AU Oliansky, DM Gordon, LI King, J Laport, G Leonard, JP McLaughlin, P Soiffer, RJ van Besien, KW Werner, M Jones, RB McCarthy, PL Hahn, T AF Oliansky, Denise M. Gordon, Leo I. King, Jerry Laport, Ginna Leonard, John P. McLaughlin, Peter Soiffer, Robert J. van Besien, Koen W. Werner, Michael Jones, Roy B. McCarthy, Philip L., Jr. Hahn, Theresa TI The Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Treatment of Follicular Lymphoma: An Evidence-Based Review SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE Follicular lymphoma; Hematopoietic stem cell transplantation; Systemic evidence-based review; Therapy; Adult ID HIGH-DOSE THERAPY; NON-HODGKINS-LYMPHOMA; BONE-MARROW-TRANSPLANTATION; TERM-FOLLOW-UP; LOW-GRADE LYMPHOMA; INTERNATIONAL PROGNOSTIC INDEX; PROGRESSION-FREE SURVIVAL; EVENT-FREE SURVIVAL; ALLOGENEIC TRANSPLANTATION; INDOLENT LYMPHOMA AB Clinical research examining the role of hematopoietic stem cell transplantation (SCT) in the therapy of follicular non-Hodgkin lymphoma in adults is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations reached unanimously by a panel of follicular lymphoma experts are: ( I) autologous SCT is recommended as salvage therapy based on pre-rituximab data, with a significant improvement in overall survival (OS) and progression-free (PFS) survival; (2) autologous SCT is not recommended as first-line treatment for most patients because of no significant improvement in OS; (3) autologous SCT is recommended for transformed follicular lymphoma patients; (4) reduced intensity conditioning before allogeneic SCT appears to be an acceptable alternative to myeloablative regimens; (5) an HLA-matched unrelated donor appears to be as effective an HLA-matched related donor for reduced intensity conditioning allogeneic SCT. There are insufficient data to make a recommendation on the use of autologous SCTafter rituximab-based salvage therapy. Eleven areas of needed research in the treatment of follicular lymphoma with SCTwere identified and are presented in the review. C1 [Oliansky, Denise M.; McCarthy, Philip L., Jr.; Hahn, Theresa] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Gordon, Leo I.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gordon, Leo I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [King, Jerry] Blue Cross & Blue Shield Illinois, Chicago, IL USA. [Laport, Ginna] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Leonard, John P.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [McLaughlin, Peter; Jones, Roy B.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Soiffer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [van Besien, Koen W.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Werner, Michael] Lymphoma Res Fdn, Chicago, IL USA. RP Hahn, T (reprint author), Roswell Pk Canc Inst, Elm & Carlton St, Buffalo, NY 14263 USA. EM Theresa.hahn@roswellpark.org RI van Besien, Koen/G-4221-2012; OI van Besien, Koen/0000-0002-8164-6211; Gordon, Leo/0000-0003-1666-7064 FU National Marrow Donor Program FX Major funding for this study was provided by the National Marrow Donor Program. The American Society for Blood and Marrow Transplantation and Drs. Hahn and McCarthy are indebted to the members of the Follicular Lymphoma Review Expert Panel and the ASBMT Evidence-Based Review Steering Committee, who voluntarily and enthusiastically participated in this endeavor. The authors of this review and the American Society for Blood and Marrow Transplantation thank the National Marrow Donor Program, and especially Jeffrey Chell, MD, and Michael Boo, for their support of this project. The authors acknowledge Dr. C. Fred Le-Maistre for pioneering and supporting this effort and Alan Leahigh and Dianne O'Rourke for their invaluable administrative assistance. The authors are grateful to all the patients who participated in the clinical trials that led to the evidence upon which this review is based. NR 85 TC 32 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2010 VL 16 IS 4 BP 443 EP 468 DI 10.1016/j.bbmt.2010.01.008 PG 26 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 578JC UT WOS:000276288600001 PM 20114084 ER PT J AU Carson, JP Kuprat, AP Jiao, XM Dyedov, V del Pin, F Guccione, JM Ratcliffe, MB Einstein, DR AF Carson, James P. Kuprat, Andrew P. Jiao, Xiangmin Dyedov, Volodymyr del Pin, Facundo Guccione, Julius M. Ratcliffe, Mark B. Einstein, Daniel R. TI Adaptive generation of multimaterial grids from imaging data for biomedical Lagrangian fluid-structure simulations SO BIOMECHANICS AND MODELING IN MECHANOBIOLOGY LA English DT Article DE Multimaterial grid generation; Micro MRI; Mouse heart; Fluid-structure interaction; Volume-conserving smoothing ID FINITE-ELEMENT-METHOD; SHEAR-STRESS; ENDOTHELIAL-CELLS; ISOGEOMETRIC ANALYSIS; PARTICLE DEPOSITION; BLOOD-FLOW; CARDIOGENESIS; NURBS AB Spatial discretization of complex imaging- derived fluid-solid geometries, such as the cardiac environment, is a critical but often overlooked challenge in biomechanical computations. This is particularly true in problems with Lagrangian interfaces, where the fluid and solid phases share a common interface geometrically. For simplicity and better accuracy, it is also highly desirable for the two phases to have a matching surface mesh at the interface between them. We outline a method for solving this problem, and illustrate the approach with a 3D fluid-solid mesh of the mouse heart. An MRI dataset of a perfusion-fixed mouse heart with 50 mu m isotropic resolution was semi-automatically segmented using a customized multimaterial connected-threshold approach that divided the volume into non-overlapping regions of blood, tissue, and background. Subsequently a multimaterial marching cubes algorithm was applied to the segmented data to produce two detailed, compatible isosurfaces, one for blood and one for tissue. Both isosurfaces were simultaneously smoothed with a multimaterial smoothing algorithm that exactly conserves the volume for each phase. Using these two isosurfaces, we developed and applied novel automated meshing algorithms to generate anisotropic hybrid meshes on arbitrary biological geometries with the number of layers and the desired element anisotropy for each phase as the only input parameters. Since our meshes adapt to the local feature sizes and include boundary layer prisms, they are more efficient and accurate than non-adaptive, isotropic meshes, and the fluid-structure interaction computations will tend to have relative error equilibrated over the whole mesh. C1 [Carson, James P.; Kuprat, Andrew P.; Einstein, Daniel R.] Pacific NW Natl Lab, Richland, WA 99352 USA. [Jiao, Xiangmin; Dyedov, Volodymyr] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [del Pin, Facundo] Livermore Software Technol Corp, Livermore, CA USA. [Guccione, Julius M.; Ratcliffe, Mark B.] San Francisco VA Med Ctr, UCSF Dept Surg, San Francisco, CA USA. RP Carson, JP (reprint author), Pacific NW Natl Lab, Richland, WA 99352 USA. EM james.carson@pnl.gov; andrew.kuprat@pnl.gov; jiao@ams.sunysb.edu; vladimir@ams.sunysb.edu; fdelpin@lstc.com; julius.guccione@va.gov; mark.ratcliffe@va.gov; daniel.einstein@pnl.gov OI Kuprat, Andrew/0000-0003-4159-918X; Jiao, Xiangmin/0000-0002-7111-9813 FU NCRR/NCI [P41 RR05959/U24 CA092656]; National Heart Lung and Blood Institute [1RO1HL073598-01A1, 1R01HL084431-01A1]; National Science Foundation [DMS-0809285]; U.S Department of Energy [LDRD DE-AC05-76RL01830] FX MR data was supplied by Dr. G. Allan Johnson, Duke Center for In Vivo Microscopy under support from NCRR/NCI (P41 RR05959/U24 CA092656). This research was funded by the National Heart Lung and Blood Institute Awards 1RO1HL073598-01A1 and 1R01HL084431-01A1, by the National Science Foundation under award number DMS-0809285, and by the U.S Department of Energy under LDRD DE-AC05-76RL01830. NR 41 TC 9 Z9 9 U1 0 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1617-7959 J9 BIOMECH MODEL MECHAN JI Biomech. Model. Mechanobiol. PD APR PY 2010 VL 9 IS 2 BP 187 EP 201 DI 10.1007/s10237-009-0170-5 PG 15 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 568TM UT WOS:000275545800006 PM 19727874 ER PT J AU Fruhwirth-Schnatter, S Pyne, S AF Fruehwirth-Schnatter, Sylvia Pyne, Saumyadipta TI Bayesian inference for finite mixtures of univariate and multivariate skew-normal and skew-t distributions SO BIOSTATISTICS LA English DT Article DE Flow cytometry; Gibbs sampling; Kurtosis; Markov chain Monte Carlo; Skewness; Stochastic representation ID CHAIN-MONTE-CARLO; FLOW-CYTOMETRY DATA; UNKNOWN NUMBER; MODELS; COMPONENTS; LIKELIHOOD AB We develop Bayesian inference based on data augmentation and Markov chain Monte Carlo (MCMC) sampling. In addition to the latent allocations, data augmentation is based on a stochastic representation of the skew-normal distribution in terms of a random-effects model with truncated normal random effects. For finite mixtures of skew normals, this leads to a Gibbs sampling scheme that draws from standard densities only. This MCMC scheme is extended to mixtures of skew-t distributions based on representing the skew-t distribution as a scale mixture of skew normals. As an important application of our new method, we demonstrate how it provides a new computational framework for automated analysis of high-dimensional flow cytometric data. Using multivariate skew-normal and skew-t mixture models, we could model non-Gaussian cell populations rigorously and directly without transformation or projection to lower dimensions. C1 [Fruehwirth-Schnatter, Sylvia] Johannes Kepler Univ Linz, Dept Appl Stat & Econometr, A-1040 Linz, Austria. [Pyne, Saumyadipta] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Fruhwirth-Schnatter, S (reprint author), Johannes Kepler Univ Linz, Dept Appl Stat & Econometr, A-1040 Linz, Austria. EM sylvia.fruehwirth-schnatter@jku.at NR 51 TC 56 Z9 57 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2010 VL 11 IS 2 BP 317 EP 336 DI 10.1093/biostatistics/kxp062 PG 20 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 564US UT WOS:000275243900011 PM 20110247 ER PT J AU Friedberg, JW Sharman, J Sweetenham, J Johnston, PB Vose, JM LaCasce, A Schaefer-Cutillo, J De Vos, S Sinha, R Leonard, JP Cripe, LD Gregory, SA Sterba, MP Lowe, AM Levy, R Shipp, MA AF Friedberg, Jonathan W. Sharman, Jeff Sweetenham, John Johnston, Patrick B. Vose, Julie M. LaCasce, Ann Schaefer-Cutillo, Julia De Vos, Sven Sinha, Rajni Leonard, John P. Cripe, Larry D. Gregory, Stephanie A. Sterba, Michael P. Lowe, Ann M. Levy, Ronald Shipp, Margaret A. TI Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia SO BLOOD LA English DT Article ID B-CELL LYMPHOMA; TYROSINE KINASE INHIBITOR; FOLLICULAR LYMPHOMA; RHEUMATOID-ARTHRITIS; THERAPEUTIC TARGET; RESPONSE CRITERIA; PHASE-III; R-CHOP; EXPRESSION; BCR AB Certain malignant B cells rely on B-cell receptor (BCR)-mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). Dose-limiting toxicity in the phase 1 portion was neutropenia, diarrhea, and thrombocytopenia, and 200 mg twice daily was chosen for phase 2 testing. Sixty-eight patients with recurrent B-NHL were then enrolled in 3 cohorts: (1) diffuse large B-cell lymphoma (DLBCL), (2) follicular lymphoma (FL), and (3) other NHL, including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue lymphoma, lymphoplasmacytic lymphomas, and small lymphocytic leukemia/chronic lymphocytic leukemia (SLL/CLL). Common toxicities included diarrhea, fatigue, cytopenias, hypertension, and nausea. Objective response rates were 22% (5 of 23) for DLBCL, 10% (2 of 21) for FL, 55% (6 of 11) for SLL/CLL, and 11% (1/9) for MCL. Median progression-free survival was 4.2 months. Disrupting BCR-induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL/CLL. This trial was registered at www.clinicaltrials.gov as # NCT00446095. (Blood. 2010;115(13):2578-2585) C1 [Friedberg, Jonathan W.; Schaefer-Cutillo, Julia] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Sharman, Jeff; Levy, Ronald] Stanford Univ, Stanford, CA 94305 USA. [Sweetenham, John] Cleveland Clin, Cleveland, OH USA. [Johnston, Patrick B.] Mayo Clin, Rochester, MN USA. [Vose, Julie M.] Univ Nebraska, Omaha, NE 68182 USA. [LaCasce, Ann; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [De Vos, Sven] Univ Calif Los Angeles, Los Angeles, CA USA. [Sinha, Rajni] Emory Univ, Atlanta, GA 30322 USA. [Leonard, John P.] Cornell Univ, New York, NY 10021 USA. [Cripe, Larry D.] Indiana Univ, Indianapolis, IN 46204 USA. [Gregory, Stephanie A.] Rush Univ, Chicago, IL 60612 USA. [Sterba, Michael P.; Lowe, Ann M.] Rigel Pharmaceut, San Francisco, CA USA. RP Friedberg, JW (reprint author), Univ Rochester, James P Wilmot Canc Ctr, 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA. EM jonathan_friedberg@urmc.rochester.edu FU Rigel Pharmaceuticals; University of Rochester [CA-130805] FX This study was supported by Rigel Pharmaceuticals. J.W.F. is a Clinical Scholar of the Leukemia & Lymphoma Society and is supported in part by the University of Rochester Specialized Program of Research Excellence (SPORE) in Lymphoma (CA-130805). NR 45 TC 414 Z9 425 U1 2 U2 36 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 1 PY 2010 VL 115 IS 13 BP 2578 EP 2585 DI 10.1182/blood-2009-08-236471 PG 8 WC Hematology SC Hematology GA 577DI UT WOS:000276201000006 PM 19965662 ER PT J AU Warden, SJ Hassett, SM Bond, JL Rydberg, J Grogg, JD Hilles, EL Bogenschutz, ED Smith, HD Fuchs, RK Bliziotes, MM Turner, CH AF Warden, Stuart J. Hassett, Sean M. Bond, Julie L. Rydberg, Johanna Grogg, Jamie D. Hilles, Erin L. Bogenschutz, Elizabeth D. Smith, Heather D. Fuchs, Robyn K. Bliziotes, M. Michael Turner, Charles H. TI Psychotropic drugs have contrasting skeletal effects that are independent of their effects on physical activity levels SO BONE LA English DT Article DE Antidepressant; Depression; Fluoxetine; Osteoporosis; Prozac ID SEROTONIN REUPTAKE INHIBITORS; BONE-MINERAL DENSITY; ANTIDEPRESSANT DRUGS; CHRONIC FLUOXETINE; GROWING RATS; IN-VITRO; TRANSPORTER; RISK; 5-HYDROXYTRYPTAMINE; RECEPTOR AB Popular psychotropic drugs, like the antidepressant selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), and the mood stabilizer lithium, may have skeletal effects. In particular, preclinical observations suggest a direct negative effect of SSRIs on the skeleton. A potential caveat in studies of the skeletal effects of psychotropic drugs is the hypoactive (skeletal unloading) phenotype they induce. The aim of this study was to investigate the contribution of physical inactivity to the skeletal effects of psychotropic drugs by studying bone changes in cage control and tail suspended mice treated with either vehicle, SSRI, TCA or lithium. Tail suspension was used to control for drug differences on physical activity levels by normalizing skeletal loading between groups. The psychotropic drugs were found to have contrasting skeletal effects which were independent of drug effects on animal physical activity levels. The latter was evident by an absence of statistical interactions between the activity and drug groups. Pharmacological inhibition of the 5-hydroxytryptamine (5-HT) transporter (5-HTT) using a SSRI reduced in vivo gains in lower extremity BMD, and negatively altered ex vivo measures of femoral and spinal bone density, architecture and mechanical properties. These effects were mediated by a decrease in bone formation without a change in bone resorption suggesting that the SSRI had anti-anabolic skeletal effects. In contrast, glycogen synthase kinase-3[beta] (GSK-3[beta]) inhibition using lithium had anabolic effects improving in vivo gains in BMD via an increase in bone formation, while TCA-mediated inhibition of the norepinephrine transporter had minimal skeletal effect. The observed negative skeletal effect of 5-HTT inhibition, combined with recent findings of direct and indirect effects of 5-HT on bone formation, are of interest given the frequent prescription of SSRIs for the treatment of depression and other affective disorders. Likewise, the anabolic effect of GSK-3[beta] inhibition using lithium reconfirms the importance of Wnt/beta-catenin signaling in the skeleton and it's targeting by recent drug discovery efforts. In conclusion, the current study demonstrates that different psychotropic drugs with differing underlying mechanisms of action have contrasting skeletal effects and that these effects do not result indirectly via the generation of animal physical inactivity. (C) 2010 Elsevier Inc. All rights reserved. C1 [Warden, Stuart J.; Hassett, Sean M.; Bond, Julie L.; Rydberg, Johanna; Grogg, Jamie D.; Hilles, Erin L.; Bogenschutz, Elizabeth D.; Smith, Heather D.; Fuchs, Robyn K.] Indiana Univ, Sch Hlth & Rehabil Sci, Dept Phys Therapy, Indianapolis, IN 46202 USA. [Fuchs, Robyn K.] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. [Warden, Stuart J.; Bliziotes, M. Michael] Portland VA Med Ctr, Portland, OR 97201 USA. [Bliziotes, M. Michael] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Warden, Stuart J.; Turner, Charles H.] Indiana Univ Purdue Univ, Purdue Sch Engn & Technol, Dept Biomed Engn, Indianapolis, IN 46202 USA. RP Warden, SJ (reprint author), Indiana Univ, Sch Hlth & Rehabil Sci, Dept Phys Therapy, 1140 W Michigan St,CF 326, Indianapolis, IN 46202 USA. EM stwarden@iupui.edu RI Warden, Stuart/C-5287-2012; OI Warden, Stuart/0000-0002-6415-4936 FU National Institutes of Health [R01 AR052018, S10 RR023710] FX The authors thank Keith W. Condon for assistance with tissue processing. This work was supported by the National Institutes of Health (R01 AR052018 and S10 RR023710). NR 43 TC 21 Z9 24 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2010 VL 46 IS 4 BP 985 EP 992 DI 10.1016/j.bone.2009.12.031 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 574RD UT WOS:000276009400016 PM 20060080 ER PT J AU Lotinun, S Pearsall, RS Davies, MV Marvell, TH Monnell, TE Ucran, J Fajardo, RJ Kumar, R Underwood, KW Seehra, J Bouxsein, ML Baron, R AF Lotinun, Sutada Pearsall, R. Scott Davies, Monique V. Marvell, Tod H. Monnell, Travis E. Ucran, Jeffrey Fajardo, Roberto J. Kumar, Ravindra Underwood, Kathryn W. Seehra, Jasbir Bouxsein, Mary L. Baron, Roland TI A soluble activin receptor Type IIA fusion protein (ACE-011) increases bone mass via a dual anabolic-antiresorptive effect in Cynomolgus monkeys SO BONE LA English DT Article DE Activin A; ActRIIA; Osteoporosis; Osteoblast; Osteoclast ID PARATHYROID-HORMONE 1-34; FACTOR-BETA FAMILY; POSTMENOPAUSAL WOMEN; MACACA-FASCICULARIS; FOLLISTATIN SYSTEM; BINDING PROTEIN; OSTEOPOROSIS; CULTURES; DIFFERENTIATION; EXPRESSION AB Activin A belongs to the TGF-beta superfamily and plays an important role in bone metabolism. It was reported that a soluble form of extracellular domain of the activin receptor type IIA (ActRIIA) fused to the Fc domain of murine IgG, an activin antagonist, has an anabolic effect on bone in intact and ovariectomized mice. The present study was designed to examine the skeletal effect of human ActRIIA-IgG1-Fc (ACE-011) in non-human primates. Young adult female Cynomolgus monkeys were given a biweekly subcutaneous injection of either 10 mg/kg ACE-011 or vehicle (VEH) for 3 months. Treatment effects were evaluated by histomorphometric analysis of the distal femur, femoral midshaft, femoral neck and 12th thoracic vertebrae, by mu CT analysis of femoral neck and by biomarkers of bone turnover. Compared to VEH, at the distal femur ACE-011-treated monkeys had significantly increased cancellous bone volume (+93%), bone formation rate per bone surface (+166%) and osteoblast surface (+196%) indicating an anabolic action. Monkeys treated with ACE-011 also had decreased osteoclast surface and number. No differences were observed in parameters of cortical bone at the midshaft of the femur. Similar to distal femur, ACE-011-treated monkeys had significantly greater cancellous bone volume, bone formation rate and osteoblast surface at the femoral neck relative to VEH. A significant increase in bone formation rate and osteoblast surface with a decrease in osteoclast surface was observed in thoracic vertebrae. mu CT analysis of femoral neck indicated more plate-like structure in ACE-011-treated monkeys. Monkeys treated with ACE-011 had no effect on serum bone-specific alkaline phosphatase and CTX at the end of the study. These observations demonstrate that ACE-011 is a dual anabolic-antiresorptive compound, improving cancellous bone volume by promoting bone formation and inhibiting bone resorption in non-human primates. Thus, soluble ActRIIA fusion protein may be useful in the prevention and/or treatment of osteoporosis and other diseases involving accelerated bone loss. (C) 2010 Elsevier Inc. All rights reserved. C1 [Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Pearsall, R. Scott; Davies, Monique V.; Marvell, Tod H.; Monnell, Travis E.; Ucran, Jeffrey; Kumar, Ravindra; Underwood, Kathryn W.; Seehra, Jasbir] Acceleron Pharma Inc, Cambridge, MA 02139 USA. [Fajardo, Roberto J.; Bouxsein, Mary L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Fajardo, Roberto J.; Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Orthoped Biomech Lab, Boston, MA 02215 USA. [Baron, Roland] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Baron, Roland] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lotinun, S (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. EM sutada_lotinun@hsdm.harvard.edu OI Lotinun, Sutada/0000-0002-5127-3039 FU Acceleron Pharma, Cambridge, MA FX The study was sponsored by Acceleron Pharma, Cambridge, MA. We thank Rajaram Manoharan for assistance with the mu CT imaging. NR 35 TC 64 Z9 66 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2010 VL 46 IS 4 BP 1082 EP 1088 DI 10.1016/j.bone.2010.01.370 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 574RD UT WOS:000276009400031 PM 20080223 ER PT J AU Patterson, EK Hodsman, AB Hendy, GN Canaff, L Bringhurst, FR Fraher, LJ AF Patterson, Eric K. Hodsman, Anthony B. Hendy, Geoffrey N. Canaff, Lucie Bringhurst, F. Richard Fraher, Laurence J. TI Functional analysis of a type 1 parathyroid hormone receptor intracellular tail mutant [KRK(484-6)AAA]: Effects on second messenger generation and cellular targeting SO BONE LA English DT Article DE PTHR1; GPCR; Intracellular signalling; Cellular localization; Green fluorescent protein ID PTH1R NUCLEAR TRAFFICKING; BETA-GAMMA-SUBUNITS; PHOSPHOLIPASE-C; (PTH)/PTH-RELATED PEPTIDE; ADENYLYL-CYCLASE; LLC-PK1 CELLS; KIDNEY-CELLS; PROTEIN; LOCALIZATION; STIMULATION AB The parathyroid hormone receptor type 1 (PTHR1) is activated by parathyroid hormone (PTH) and PTH-related protein (PTHrP) and primarily signals via intracellular pathways involving adenylyl cyclase and phospholipase C. The intracellular tail domain of the PTHR1 contributes to G protein subunit coupling that is important for second messenger signalling. In addition, the intracellular domain has a potential nuclear localization sequence (NLS) that, if functional, could point to an intracrine role for the receptor. In the present study, we have utilized 2 sets of constructs that employ either a [KRK(484-486)AAA](3AlA) mutation in the putative NLS or the non-mutant counterpart and included (a) the full-length rat PTHR1 with FLAG and c-myc epitope tags at the N-terminus and C-terminus, respectively (designated as PTHR1(3AlA)-TAG and PTHR1-TAG); and (b) only the putative NLS-containing intracellular domain (471-488), with green fluorescent protein (GFP) fused to the C-terminus (designated as GFP-(3AlA)471-488 or GFP-471-488). Porcine kidney LIC-PK1 cells stably expressing the PTHR1 (3AlA)-TAG exhibited reduced signalling via both cAMP and cytosolic calcium transients in spite of greater cell surface expression relative to cells expressing PTHR1-TAG. We also examined the ability of the intracellular tail to influence the cellular localization of a heterologous protein. LLC-PK1 cells transiently transfected with GFP-471-488, exhibited increased fluorescence within the nucleus, relative to cells transfected with GFP alone that was not observed when cells were transiently transfectecl with the mutated construct, GFP-(3AlA)471-488. However, LLC-PK1 cells transiently transfected with either the full-length PTHR1-TAG or the PTHR1(3AlA)-TAG constructs did not exhibit nuclear localization of these receptors. Moreover, mouse osteoblast-like cells (MC3T3-E1) transiently expressing PTHR1-TAG also failed to demonstrate nuclear localization, although both full-length PTHR1 constructs exhibited plasma membrane immunofluorescence in both cell lines. Thus, the 484-486 sequence is critical for the full signalling responsiveness of the intact PTHR1, but the putative nuclear localization signal may not function as such within the intact receptor. (C) 2010 Elsevier Inc. All rights reserved. C1 [Patterson, Eric K.; Hodsman, Anthony B.; Fraher, Laurence J.] St Josephs Hlth Care, Lawson Hlth Res Inst, London, ON N6A 4V2, Canada. [Patterson, Eric K.; Fraher, Laurence J.] Univ Western Ontario, Dept Biochem, London, ON N6A 4V2, Canada. [Hodsman, Anthony B.; Fraher, Laurence J.] Univ Western Ontario, Dept Med, London, ON N6A 4V2, Canada. [Hendy, Geoffrey N.; Canaff, Lucie] McGill Univ, Royal Victoria Hosp, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. [Bringhurst, F. Richard] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bringhurst, F. Richard] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Fraher, LJ (reprint author), St Josephs Hlth Care, Lawson Hlth Res Inst, Room E4-158,268 Grosvenor St, London, ON N6A 4V2, Canada. EM lfraher@lri.sjhc.london.on.ca OI Patterson, Eric/0000-0003-3697-3042 FU Canadian Institutes of Health Research [MOP 37984] FX The authors would like to thank Benoit Lewden for automating the analysis of the calcium measurements, Dr. Stephen Sims and Dr. Jeff Dixon for critical review of the manuscript and help in the calcium measurements, Tom Chrones, Danielle Lapierre and Elizabeth Pruski for their help in the calcium measurements and Clare Poschwatta for help in creating the GFP-471-488 plasmid. These studies were funded by the Canadian Institutes of Health Research, grant number MOP 37984. NR 30 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2010 VL 46 IS 4 BP 1180 EP 1187 DI 10.1016/j.bone.2009.12.005 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 574RD UT WOS:000276009400043 PM 20006743 ER PT J AU Cheung, AK Chen, MH Moran, BJ Braccioforte, MH Dosoretz, DE Salenius, S Katin, M Ross, R D'Amico, AV AF Cheung, Arthur K. Chen, Ming-Hui Moran, Brian J. Braccioforte, Michelle H. Dosoretz, Daniel E. Salenius, Sharon Katin, Michael Ross, Rudi D'Amico, Anthony V. TI The use of supplemental external beam radiotherapy in men with low-risk prostate cancer undergoing brachytherapy before and after the 1999 American Brachytherapy Society Guideline statement SO BRACHYTHERAPY LA English DT Article DE Prostate cancer; Brachytherapy; External beam radiation therapy; Patterns of care ID QUALITY-OF-LIFE; CLINICAL-PRACTICE GUIDELINES; RADICAL PROSTATECTOMY; SIMULTANEOUS IRRADIATION; RADIATION-THERAPY; UNITED-STATES; CARCINOMA; CARE; MANAGEMENT; PATTERNS AB PURPOSE: In 1999, the American Brachytherapy Society (ABS) recommended brachy-monotherapy for men with low-risk prostate cancer because of the potential for increased toxicity with combined external beam radiotherapy (EBRT) and brachytherapy without the proof of increased efficacy. We investigated the patterns of care in the community in this patient population before and after the reporting of the ABS guideline. METHODS AND MATERIALS: The study cohort consisted of 4943 men (median age, 69.0 years) with low-risk prostate cancer treated with brachytherapy with or without supplemental EBRT from 1991 to 2007 across 21 community radiation oncology centers. Multivariable logistic regression analysis was performed to determine if there was a significant association between the year of brachytherapy, prostate-specific antigen level, clinical tumor (T) category, patient's age, and the use of supplemental EBRT. RESULTS: Supplemental EBRT was used in 647 men (13%). The EBRT use initially increased until 2001 and then decreased yielding a significant association (adjusted odds ratio [AOR], 0.92; p <0.001) between the EBRT use and the year of brachytherapy using a quadratic formulation. Specifically, EBRT use peaked at 24.6% in 2001 and subsequently declined to 3.3% by 2007. Men with clinical category T2a as compared with Tic disease (AOR, 1.43; p <0.001) were more likely to receive combined modality therapy. CONCLUSIONS: The use of supplemental EBRT in men with low-risk prostate cancer treated with brachytherapy has decreased since 2001. This change in practice patterns suggests gradual adoption of the 1999 ABS practice guidelines. (C) 2010 Published by Elsevier Inc. on behalf of American Brachytherapy Society. C1 [Cheung, Arthur K.; D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Cheung, Arthur K.; D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Moran, Brian J.; Braccioforte, Michelle H.] Prostate Canc Fdn Chicago, Dept Radiat Oncol, Westmont, IL USA. [Dosoretz, Daniel E.; Salenius, Sharon; Katin, Michael; Ross, Rudi] 21st Century Oncol, Ft Myers, FL USA. RP Cheung, AK (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI L2, Boston, MA 02115 USA. EM acheung@lroc.harvard.edu NR 34 TC 3 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD APR-JUN PY 2010 VL 9 IS 2 BP 145 EP 150 DI 10.1016/j.brachy.2009.08.001 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 587SD UT WOS:000277012000008 PM 20346894 ER PT J AU Chu-Shore, CJ Thiele, EA AF Chu-Shore, Catherine J. Thiele, Elizabeth A. TI Tumor growth in patients with tuberous sclerosis complex on the ketogenic diet SO BRAIN & DEVELOPMENT LA English DT Article DE Tuberous sclerosis complex; TSC; Ketogenic diet; mTOR; Subependymal giant cell tumor; Angiomyolipoma; Nutrition ID MUTATIONAL ANALYSIS; CELL-GROWTH; AMINO-ACID; MTOR; TSC2; SIROLIMUS; RAPAMYCIN; CANCER; LYMPHANGIOLEIOMYOMATOSIS AB Purpose: New evidence is emerging that the availability of nutrients plays a key role in regulating the mammalian target of rapamycin complex-1 (mTORC1) signaling pathway in human cancers. Tuberous sclerosis complex (TSC) is a genetic disorder which results in the growth of hamartomatous lesions in multiple organs due to insufficient suppression of the mTORC1 pathway. A minority of patients with TSC who develop epilepsy which is intractable to standard anticonvulsant medical and/or surgical treatments are treated with the ketogenic diet. To provide insight into the effects of nutrient manipulation on tumor growth in this condition, we describe our experience in a unique group of patients with known tuberous sclerosis complex who are on the ketogenic diet for seizure control. Methods: A retrospective chart review was performed of patients with TSC treated with the ketogenic diet between January 2002 and May 2007 at Massachusetts General Hospital. Results: Five patients with definite TSC underwent serial imaging for tumor growth while on the ketogenic diet or had unchanged imaging prior to the onset of the diet and after termination. Three Out of five patients, all children, had progression of a known tumor or tumors or the development of a new tumor while on the ketogenic diet. Conclusion: In this limited case series of five TSC patients, the ketogenic diet did not induce tumor regression or suppress the growth of TSC-related tumors. (C) 2009 Elsevier B.V. All rights reserved. C1 [Chu-Shore, Catherine J.; Thiele, Elizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org NR 25 TC 11 Z9 14 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0387-7604 J9 BRAIN DEV-JPN JI Brain Dev. PD APR PY 2010 VL 32 IS 4 BP 318 EP 322 DI 10.1016/j.braindev.2009.04.009 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 572OM UT WOS:000275842400009 PM 19443154 ER PT J AU Freedman, RA Winer, EP AF Freedman, Rachel A. Winer, Eric P. TI Adjuvant therapy for postmenopausal women with endocrine-sensitive breast cancer SO BREAST LA English DT Review DE Adjuvant endocrine therapy; Postmenopausal ID RANDOMIZED-TRIAL; AROMATASE INHIBITORS; CYCLOOXYGENASE-2 INHIBITORS; TAMOXIFEN THERAPY; COMBINATION TRIAL; ANASTROZOLE; STAGE; RECURRENCE; LETROZOLE; CHEMOTHERAPY AB Approximately 180,000 women are diagnosed with breast cancer in the United States annually. The majority of these women are postmenopausal and have endocrine-sensitive tumors. Over the last four decades, multiple clinical trials have been conducted in efforts to establish and advance adjuvant endocrine therapies. We review the available evidence for adjuvant endocrine therapies and current recommendations for therapy in postmenopausal women. Although we have made substantial progress in the treatment of endocrine-sensitive breast cancer, future study will require incorporation of biological and translational questions with the goal of enhancing treatment benefits and minimizing toxicity. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Freedman, Rachel A.; Winer, Eric P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM rafreedman@partners.org; ewiner@partners.org NR 66 TC 9 Z9 9 U1 2 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD APR PY 2010 VL 19 IS 2 BP 69 EP 75 DI 10.1016/j.breast.2009.11.009 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 597YG UT WOS:000277797900001 PM 20034796 ER PT J AU Dunlap, J Le, C Shukla, A Patterson, J Presnell, A Heinrich, MC Corless, CL Troxell, ML AF Dunlap, Jennifer Le, Claudia Shukla, Arielle Patterson, Janice Presnell, Ajia Heinrich, Michael C. Corless, Christopher L. Troxell, Megan L. TI Phosphatidylinositol-3-kinase and AKT1 mutations occur early in breast carcinoma SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Phosphatidylinositol-3-kinase (PIK3CA); AKT1; Breast carcinoma; Carcinoma in situ; Laser capture microdissection ID CANCER-SPECIFIC MUTATIONS; MAMMARY EPITHELIAL-CELLS; PIK3CA GENE-MUTATIONS; HIGH-FREQUENCY; ENDOMETRIAL CARCINOMA; 3'-KINASE PATHWAY; PI3K/AKT PATHWAY; DRUG DISCOVERY; PTEN LOSS; 3-KINASE AB Mutationally activated protein kinases are appealing therapeutic targets in breast carcinoma. Mutations in phosphatidylinositol-3-kinase (PI3KCA) have been described in 8-40% of invasive breast carcinomas, and AKT1 mutations have been characterized in 1-8% of breast carcinomas. However, there is little data on these mutations in breast precursor lesions. To further delineate the molecular evolution of breast tumorigenesis, samples of invasive breast carcinoma with an accompanying in situ component were macro dissected from formalin-fixed paraffin embedded tissue and screened for mutations in PIK3CA exons 7, 9, 20, and AKT1 exon 2. Laser capture micro dissection (LCM) was performed on mutation-positive carcinomas to directly compare the genotypes of separated invasive and in situ tumor cells. Among 81 cases of invasive carcinoma, there were eight mutations in PIK3CA exon 20 (7 H1047R, 1 H1047L) and four mutations in exon 9 (2 E545K, 1 E542K, 1 E545G), totaling 12/81 (14.8%). In 11 cases examined, paired LCM in situ tumor showed the identical PIK3CA mutation in invasive and in situ carcinoma. Likewise, 3 of 78 (3.8%) invasive carcinomas showed an AKT1 E17K mutation, and this mutation was identified in matching in situ carcinoma in both informative cases. Mutational status did not correlate with clinical parameters including hormone receptor status, grade, and lymph node status. The complete concordance of PIK3CA and AKT1 mutations in matched samples of invasive and in situ tumor indicates that these mutations occur early in breast cancer development and has implications with regard to therapeutics targeted to the PI3 kinase pathway. C1 [Dunlap, Jennifer; Corless, Christopher L.; Troxell, Megan L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Le, Claudia; Shukla, Arielle; Patterson, Janice; Presnell, Ajia; Heinrich, Michael C.; Corless, Christopher L.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Dept Med, Portland, OR 97239 USA. RP Troxell, ML (reprint author), Oregon Hlth & Sci Univ, Dept Pathol, L471,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM troxellm@ohsu.edu OI Patterson, Janice/0000-0002-8969-2933 FU Department of Veterans Affairs; OHSU Medical Research Foundation FX The authors wish to acknowledge expert technical assistance of Carolyn Gendron, Rebecca Lewis, Judith Levine, Carol Beadling, and Andrea Warrick. Dr. Terry Morgan provided assistance with the statistical calculations. This work was supported in part by a VA Merit Review Grant from the Department of Veterans Affairs (MCH) and by a grant from the OHSU Medical Research Foundation. NR 50 TC 66 Z9 66 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 2010 VL 120 IS 2 BP 409 EP 418 DI 10.1007/s10549-009-0406-1 PG 10 WC Oncology SC Oncology GA 569WK UT WOS:000275633300014 PM 19418217 ER PT J AU Cigler, T Tu, D Yaffe, MJ Findlay, B Verma, S Johnston, D Richardson, H Hu, H Qi, S Goss, PE AF Cigler, T. Tu, D. Yaffe, M. J. Findlay, B. Verma, S. Johnston, D. Richardson, H. Hu, H. Qi, S. Goss, P. E. TI A randomized, placebo-controlled trial (NCIC CTG MAP1) examining the effects of letrozole on mammographic breast density and other end organs in postmenopausal women SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Aromatase inhibitor; Letrozole; Mammographic breast density; Clinical trial; Bone mineral density; Lipids; Bone biomarkers ID HORMONE REPLACEMENT THERAPY; CIRCULATING SEX-HORMONES; IGF-BINDING PROTEIN-3; BONE-MINERAL DENSITY; GROWTH-FACTOR-I; CANCER RISK; PARENCHYMAL PATTERNS; ADJUVANT TAMOXIFEN; NORWEGIAN WOMEN; PLASMA-LIPIDS AB Mammographically detected breast density has been correlated with breast cancer risk. Breast density appears to be influenced by hormonal factors including increasing age, postmenopausal status, number of pregnancies, lower body weight, hormone replacement therapy, and tamoxifen therapy. The aromatase inhibitor letrozole profoundly reduces breast and circulating estrogen levels in postmenopausal women. We hypothesize that letrozole may reduce breast density and report here on its effects on mammographic breast density, bone mineral density (BMD), bone biomarkers, plasma hormone, and serum lipid levels. MAP1 was a multicenter, randomized, double-blind, placebo-controlled, feasibility trial in which postmenopausal women with or without prior invasive breast cancer were randomized in a 2:1 ratio of letrozole (2.5 mg daily) or placebo for 12 months and followed for a total of 24 months. Eligible women had an estimated > 25% breast density on baseline mammogram. The primary endpoint was change in percent breast density (PD) between the baseline and 12-month mammograms as estimated by a computer-assisted thresholding program. Baseline and 12-month mammographic density was also assessed in a blinded manner by visual inspection. Secondary endpoints included changes in serum hormones, plasma lipid levels, bone biomarkers, and BMD. Data are available for 67 women (44 on letrozole and 23 on placebo). No significant changes in PD were noted between the treatment arms at either 12 or 24 months. No distinguishable difference in density measurements by visual inspection were noted between baseline and 12-month mammograms. A significant decrease in percentage change in T-score of the femoral neck at 12 months was noted in the letrozole arm without other significant changes in BMD parameters. Lipid values did not differ between treatment groups except for a borderline significant decrease in total cholesterol at 3 months among women treated with letrozole. Letrozole therapy was associated with a significant reduction in mean serum estradiol, estrone, and estrone sulfate levels at 12 months, but not at 24 months. A significant increase in serum IGF-1 levels was also noted in the letrozole group compared to the placebo group at both 12 and 24 months. To conclude, compared with placebo, 12 months of letrozole therapy does not appear to have a significant effect on mammographic PD. Twelve months of letrozole was associated with a decrease of uncertain clinical significance in the T-score of the femoral neck at 12 months which was reversible at 24 months with recovery of estrogen levels. Letrozole therapy was found to increase IGF-1 levels at 12 and 24 months. C1 [Cigler, T.] Weill Cornell Med Coll, New York, NY USA. [Tu, D.; Johnston, D.; Richardson, H.] Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. [Yaffe, M. J.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Findlay, B.] Niagara Hlth Syst, St Catharines, ON, Canada. [Verma, S.] Ottawa Hosp, Ottawa, ON, Canada. [Hu, H.; Qi, S.; Goss, P. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cigler, T (reprint author), Weill Cornell Med Coll, New York, NY USA. EM tessa@post.harvard.edu NR 47 TC 25 Z9 26 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 2010 VL 120 IS 2 BP 427 EP 435 DI 10.1007/s10549-009-0662-0 PG 9 WC Oncology SC Oncology GA 569WK UT WOS:000275633300017 PM 19967558 ER PT J AU Antonio, ALM Crespi, CM AF Antonio, Anna Liza M. Crespi, Catherine M. TI Predictors of interobserver agreement in breast imaging using the Breast Imaging Reporting and Data System SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Review DE Interobserver agreement; Kappa; Mammography; Breast cancer; BI-RADS ID FIELD DIGITAL MAMMOGRAPHY; SCREEN-FILM MAMMOGRAPHY; BIOPSY RECOMMENDATIONS; OBSERVER VARIABILITY; CANCER; MICROCALCIFICATIONS; LESIONS; CLASSIFICATION; CONCORDANCE; ULTRASOUND AB The Breast Imaging Reporting and Data System (BI-RADS) was introduced in 1993 to standardize the interpretation of mammograms. Though many studies have assessed the validity of the system, fewer have examined its reliability. Our objective is to identify predictors of reliability as measured by the kappa statistic. We identified studies conducted between 1993 and 2009 which reported kappa values for interpreting mammograms using any edition of BI-RADS. Bivariate and multivariate multilevel analyses were used to examine associations between potential predictors and kappa values. We identified ten eligible studies, which yielded 88 kappa values for the analysis. Potential predictors of kappa included: whether or not the study included negative cases, whether single- or two-view mammograms were used, whether or not mammograms were digital versus screen-film, whether or not the fourth edition of BI-RADS was utilized, the BI-RADS category being evaluated, whether or not readers were trained, whether or not there was an overlap in readers' professional activities, the number of cases in the study and the country in which the study was conducted. Our best multivariate model identified training, use of two-view mammograms and BI-RADS categories (masses, calcifications, and final assessments) as predictors of kappa. Training, use of two-view mammograms and focusing on mass description may be useful in increasing reliability in mammogram interpretation. Calcification and final assessment descriptors are areas for potential improvement. These findings are important for implementing policies in BI-RADS use before introducing the system in different settings and improving current implementations. C1 [Antonio, Anna Liza M.; Crespi, Catherine M.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Antonio, Anna Liza M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Crespi, Catherine M.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA. RP Antonio, ALM (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. EM aantonio@ucla.edu OI Crespi, Catherine/0000-0002-6150-2181 FU NIH [CA 16042] FX Crespi was supported by NIH CA 16042. NR 41 TC 13 Z9 13 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 2010 VL 120 IS 3 BP 539 EP 546 DI 10.1007/s10549-010-0770-x PG 8 WC Oncology SC Oncology GA 571LH UT WOS:000275752800002 PM 20300960 ER PT J AU Sankaran, VG Xu, J Orkin, SH AF Sankaran, Vijay G. Xu, Jian Orkin, Stuart H. TI Advances in the understanding of haemoglobin switching SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE haemoglobin switching; globin gene regulation; fetal haemoglobin; B-cell lymphoma; leukaemia 11A; GATA1 ID BETA-GLOBIN GENE; KRUPPEL-LIKE FACTOR; TRANSCRIPTION FACTOR GATA-1; SICKLE-CELL-DISEASE; LOCUS-CONTROL REGION; CHROMATIN-REMODELING COMPLEX; SITE-SPECIFIC ACETYLATION; ORPHAN NUCLEAR RECEPTORS; QUANTITATIVE TRAIT LOCUS; PRIMARY ERYTHROID-CELLS AB P>The study of haemoglobin switching has represented a focus in haematology due in large part to the clinical relevance of the fetal to adult haemoglobin switch for developing targeted approaches to ameliorate the severity of the beta-haemoglobinopathies. Additionally, the process by which this switch occurs represents an important paradigm for developmental gene regulation. In this review, we provide an overview of both the embryonic primitive to definitive switch in haemoglobin expression, as well as the fetal to adult switch that is unique to humans and old world monkeys. We discuss the nature of these switches and models of their regulation. The factors that have been suggested to regulate this process are then discussed. With the increased understanding and discovery of molecular regulators of haemoglobin switching, such as BCL11A, new avenues of research may lead ultimately to novel therapeutic, mechanism-based approaches to fetal haemoglobin reactivation in patients. C1 [Sankaran, Vijay G.; Xu, Jian; Orkin, Stuart H.] Harvard Univ, Dana Farber Canc Inst, Harvard Stem Cell Inst, Dept Pediat Oncol,Med Sch, Boston, MA 02115 USA. [Sankaran, Vijay G.; Xu, Jian; Orkin, Stuart H.] Harvard Univ, Childrens Hosp Boston, Div Hematol Oncol, Sch Med, Boston, MA 02115 USA. [Xu, Jian; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Dana Farber Canc Inst, Harvard Stem Cell Inst, Dept Pediat Oncol,Med Sch, 44 Binney St, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu FU Howard Hughes Medical Institute; NHLBI NIH HHS [R01 HL032259, P01 HL032262] NR 155 TC 79 Z9 79 U1 0 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2010 VL 149 IS 2 BP 181 EP 194 DI 10.1111/j.1365-2141.2010.08105.x PG 14 WC Hematology SC Hematology GA 572YC UT WOS:000275872500002 PM 20201948 ER PT J AU Schoessow, K AF Schoessow, Kimberly TI Shifting from compensation to participation: a model for occupational therapy in low vision SO BRITISH JOURNAL OF OCCUPATIONAL THERAPY LA English DT Review DE Vision rehabilitation; age-related eye; conditions AB Older adults with low vision present unique challenges to occupational therapists because they are generally independent in self-care but limited in leisure, productivity and instrumental activities of daily living. This paper presents a review of the needs of older adults with low vision and proposes a model for occupational therapists. A comprehensive MEDLINE search (1990-2009) of the literature on the interaction between low vision and intrinsic and extrinsic factors was performed. Titles and abstracts were reviewed and all relevant full articles were selected. Additionally, manual searches were conducted of related occupational therapy literature. The literature review found that low vision rehabilitation focuses on technology and modifying the physical environment, but that there is a great impact on older adults with low vision by intrinsic and extrinsic issues such as cognition, psychology, physiology, spirituality and the social environment. The model proposes expanding occupational therapy with low vision clients to focus comprehensively on participation and integration in the home and community. A sample measurement model for occupational therapy evaluation is provided. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Vis Rehabil Ctr, Boston, MA 02114 USA. RP Schoessow, K (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Vis Rehabil Ctr, 243 Charles St, Boston, MA 02114 USA. EM k.schoessow@gmail.com NR 87 TC 8 Z9 8 U1 2 U2 6 PU COLL OCCUPATIONAL THERAPISTS LTD PI SOUTHWARK PA 106-114 BOROUGH HIGH ST, SOUTHWARK, LONDON SE1 1LB, ENGLAND SN 0308-0226 EI 1477-6006 J9 BRIT J OCCUP THER JI Br. J. Occup. Ther. PD APR PY 2010 VL 73 IS 4 BP 160 EP 169 DI 10.4276/030802210X12706313443947 PG 10 WC Rehabilitation SC Rehabilitation GA V26AM UT WOS:000208518500004 ER PT J AU Litzenberger, JB Kim, JB Tummala, P Jacobs, CR AF Litzenberger, Julie B. Kim, Jae-Beom Tummala, Padmaja Jacobs, Christopher R. TI beta(1) Integrins Mediate Mechanosensitive Signaling Pathways in Osteocytes SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE Integrin; Mechanotransduction; Osteocyte; Fluid flow; Bone ID OSCILLATORY FLUID-FLOW; BONE-FORMATION; SHEAR-STRESS; MC3T3-E1 OSTEOBLASTS; ADHESION KINASE; TRANSGENIC MICE; PROTEIN-KINASE; PGE(2) RELEASE; ACTIVATION; CALCIUM AB Integrins are cell-substrate adhesion proteins that initiate intracellular signaling and may serve as mechanosensors in bone. MLO-Y4 cells were stably transfected with a dominant negative form of the beta(1) integrin subunit (beta 1DN) containing the transmembrane domain and cytoplasmic tail of beta(1) integrin. Cells expressing beta 1DN had reduced vinculin localization to focal contacts but no change in intracellular actin organization. When exposed to oscillatory fluid flow, beta 1DN cells exhibited a significant reduction in the upregulation of cyclooxygenase-2 gene expression and prostaglandin E-2 release. Similarly, the ratio of receptor activator of NF-kappa B ligand mRNA to osteoprotegerin mRNA decreased significantly after exposure to fluid flow in control cells but not in beta 1DN cells. Interfering with integrin signaling did not affect mechanically induced intracellular calcium mobilization. These data suggest that integrins may initiate the cellular response of osteocytes to dynamic fluid flow and may serve as mechanosensitive molecules in bone. C1 [Jacobs, Christopher R.] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. [Litzenberger, Julie B.; Tummala, Padmaja] US Dept Vet Affairs, Bone & Joint Rehabil Ctr, Palo Alto, CA USA. [Litzenberger, Julie B.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Kim, Jae-Beom] Univ Calif, Dept Stomatol, Stanford, CA USA. [Kim, Jae-Beom] Caliper Life Sci, Alameda, CA USA. [Tummala, Padmaja] MedImmune Vaccines, Mountain View, CA USA. RP Jacobs, CR (reprint author), Columbia Univ, Dept Biomed Engn, 500 W 120th St,351 Engn Terrace, New York, NY 10027 USA. EM Julitzy@gmail.com; christopher.jacobs@columbia.edu FU NIAMS NIH HHS [AR45989, R01 AR045989, R01 AR045989-10, R21 AR054156, R21 AR054156-02] NR 37 TC 37 Z9 38 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD APR PY 2010 VL 86 IS 4 BP 325 EP 332 DI 10.1007/s00223-010-9343-6 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 575DO UT WOS:000276046900006 PM 20213106 ER PT J AU Bhatt, RS Merchan, J Parker, R Wu, HK Zhang, L Seery, V Heymach, JV Atkins, MB McDermott, D Sukhatme, VP AF Bhatt, Rupal S. Merchan, Jaime Parker, Robert Wu, Hua-Kang Zhang, Liang Seery, Virginia Heymach, John V. Atkins, Michael B. McDermott, David Sukhatme, Vikas P. TI A Phase 2 Pilot Trial of Low-Dose, Continuous Infusion, or "Metronomic" Paclitaxel and Oral Celecoxib in Patients With Metastatic Melanoma SO CANCER LA English DT Article DE metastatic; melanoma; metronomic; cyclooxygenase 2; clinical trial; phase 2 ID CHEMOTHERAPY; CANCER; INHIBITION; ANGIOGENESIS; COMBINATION; THERAPY; DRUGS; TUMOR AB BACKGROUND: Tumor angiogenesis has been associated with a poor prognosis in patients with metastatic melanoma (MM). Microtubule stabilizers and cyclooxygenase 2 (COX-2) inhibitors, alone and in combination, have produced inhibitory effects on endothelial cells and tumor angiogenesis. Angiogenesis, which is the growth of new blood vessels, is necessary for tumor growth and progression. Thus, the authors tested the safety and efficacy of a low dose of paclitaxel and celecoxib in patients with MM. METHODS: Patients received paclitaxel 10 mg/m(2) for 96 hours weekly as a continuous intravenous infusion and oral celecoxib 400 mg twice daily. Systemic tumor response was assessed at 6-week intervals. Tumor measurements at the end of Cycle 1 were used as the baseline for assessment of tumor progression. Patients with unacceptable toxicity or disease progression after Cycle 2 relative to the end of Cycle 1 were taken off study. RESULTS: Twenty patients were enrolled. Twelve of 20 patients (60%) had received >= 2 previous systemic therapies. Three patients did not receive treatment because of rapid disease progression. Treatment-related grade 3/4 toxicities were limited to catheter-related complications. One patient achieved a partial response, and 3 of 20 patients (15%) had stable disease for >6 months. The median time to progression was 57 days (95% confidence interval, 43-151 days), and the median overall survival was 212 days (95% confidence interval, 147-811 days). CONCLUSIONS: Low-dose, continuous intravenous infusion paclitaxel and oral celecoxib produced disease stabilization in a significant proportion of heavily pretreated patients with MM. These findings support a role for metronomic therapy in patients with this disease. Cancer 2010;116:1751-6. (C) 2010 American Cancer Society. C1 [Bhatt, Rupal S.; McDermott, David] Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Dept Med, Boston, MA 02215 USA. [Merchan, Jaime] Univ Miami, Dept Hematol & Oncol, Miami, FL USA. [Parker, Robert] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wu, Hua-Kang; Heymach, John V.] Univ Texas MD Anderson Canc Ctr, Dept Oncol, Houston, TX 77030 USA. [Atkins, Michael B.] Dana Farber Harvard Canc Ctr, Dept Hematol & Oncol, Boston, MA USA. RP Bhatt, RS (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Dept Med, 375 Longwood Ave,Suite 476, Boston, MA 02215 USA. EM rbhatt@bidmc.harvard.edu FU NIH [R21 CA097730-01A1]; Pfizer Inc; Beth Israel Deaconess Medical Center-Harvard/MIT Health Sciences and Technology FX Supported by NIH R21 CA097730-01A1 and by a grant from Pfizer Inc. R.S.B. was funded by the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center-Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Company. NR 22 TC 39 Z9 40 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2010 VL 116 IS 7 BP 1751 EP 1756 DI 10.1002/cncr.24902 PG 6 WC Oncology SC Oncology GA 574IV UT WOS:000275983500018 PM 20120033 ER PT J AU Alderman, AK Collins, ED Schott, A Hughes, ME Ottesen, RA Theriault, RL Wong, YN Weeks, JC Niland, JC Edge, SB AF Alderman, Amy K. Collins, E. Dale Schott, Anne Hughes, Melissa E. Ottesen, Rebecca A. Theriault, Richard L. Wong, Yu-Ning Weeks, Jane C. Niland, Joyce C. Edge, Stephen B. TI The Impact of Breast Reconstruction on the Delivery of Chemotherapy SO CANCER LA English DT Article DE breast reconstruction; breast cancer; chemotherapy; NCCN ID ADJUVANT CHEMOTHERAPY; IMMEDIATE RECONSTRUCTION; PSYCHOSOCIAL OUTCOMES; CANCER; MASTECTOMY; COMPLICATIONS; DETERMINANTS; EXPERIENCE; MORBIDITY; RADIATION AB BACKGROUND: The purpose of this study was to evaluate the impact of postmastectomy breast reconstruction on the timing of chemotherapy. METHODS: The authors included stage I-Ill breast cancer patients from 8 National Comprehensive Cancer Network institutions for whom guidelines recommended chemotherapy. Surgery type was categorized as breast-conserving surgery (BCS), mastectomy alone, mastectomy with immediate reconstruction (M + IR), or mastectomy with delayed reconstruction (M + DR). A Cox regression analysis was used to assess the association between surgery type and timing of chemotherapy initiation. RESULTS: Of the 3643 patients, only 5.1% received it >= 8 weeks from surgery. In the multivariate analysis, higher stage, Caucasian and Hispanic race/ethnicity, lower body mass index, and absence of comorbid conditions were all significantly associated with earlier time to chemotherapy. There was also significant interaction among age, surgery, and chemotherapy delivery. Among women <60, time to chemotherapy was shorter for all surgery types compared with M + IR (statistical significant for all surgery types in the youngest age group and for BCS in women 40 to <50 years old). In contrast, among women >= 60, time to chemotherapy was shorter among women receiving M + IR or M + DR compared with those undergoing BCS or mastectomy alone, a difference that was statistically significant for the M + IR versus BCS comparison. CONCLUSIONS: Immediate postmastectomy breast reconstruction does not appear to lead to omission of chemotherapy, but it is associated with a modest, but statistically significant, delay in initiating treatment. For most, it is unlikely that this delay has any clinical significance. Cancer 2010;116:1791-800. (C) 2010 American Cancer Society. C1 [Alderman, Amy K.] Univ Michigan, Taubman Ctr 2130, Med Ctr, Sect Plast Surg,Dept Surg, Ann Arbor, MI 48109 USA. [Collins, E. Dale] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Surg, Hanover, NH 03756 USA. [Schott, Anne] Univ Michigan, Div Hematol Oncol, Dept Internal Med, Ann Arbor, MI 48109 USA. [Hughes, Melissa E.; Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ottesen, Rebecca A.; Niland, Joyce C.] City Hope Natl Med Ctr, Dept Informat Sci, Duarte, CA 91010 USA. [Theriault, Richard L.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Edge, Stephen B.] SUNY Buffalo, Dept Surg, Buffalo, NY 14260 USA. RP Alderman, AK (reprint author), Univ Michigan, Taubman Ctr 2130, Med Ctr, Sect Plast Surg,Dept Surg, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM aalder@umich.edu FU Robert Wood Johnson Foundation; National Cancer Institute [P50 CA89393] FX This work was supported by a grant from the Robert Wood Johnson Foundation and P50 CA89393 from the National Cancer Institute to Dana-Farber Cancer Institute. The authors have no financial or commercial interests related to this research. NR 38 TC 34 Z9 38 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2010 VL 116 IS 7 BP 1791 EP 1800 DI 10.1002/cncr.24891 PG 10 WC Oncology SC Oncology GA 574IV UT WOS:000275983500023 PM 20143440 ER PT J AU Spencer, R Nilsson, M Wright, A Pirl, W Prigerson, H AF Spencer, Ryan Nilsson, Matthew Wright, Alexi Pirl, William Prigerson, Holly TI Anxiety Disorders in Advanced Cancer Patients Correlates and Predictors of End-of-Life Outcomes SO CANCER LA English DT Article DE anxiety; anxiety disorders; end of life; palliative care; physician-patient relationship; neoplasm ID KARNOFSKY PERFORMANCE STATUS; PSYCHIATRIC MORBIDITY; DEPRESSION; CARE; RECOGNITION; RELIABILITY; VALIDATION AB BACKGROUND: The authors explored associations between anxiety disorders and advanced cancer patients' physical performance status, physician-patient relationships, end-of-life (EOL) treatment preferences and outcomes, and quality of death. METHODS: The Coping with Cancer study was a National Cancer Institute/National Institute of Mental Health-sponsored, prospective, longitudinal, multicenter cohort study of patients with advanced cancer. Six hundred thirty-five patients completed the anxiety disorders module of the Structured Clinical Interview for the Diagnostic Statistical Manual IV. The results were compared with patients' baseline physical performance status, treatment preferences, perceptions of the physician-patient relationship, and advance care planning (ACP). RESULTS: Approximately 7.6% of patients met criteria for an anxiety disorder. Patients who were diagnosed with an anxiety disorder were more likely to be women and younger and to have a worse physical performance status. Although there were no significant differences in patients' EOL treatment preferences or care, ACP, hospice enrollment, or patients' location of death, there were significant differences in how patients with anxiety disorders perceived the physician-patient relationship. Patients with anxiety disorders had less trust in their physicians, felt less comfortable asking questions about their health, and felt less likely to understand the clinical information that their physicians presented. They also were more likely to believe that their physicians would offer them futile therapies and would not adequately control their symptoms. CONCLUSIONS: Women, patients who were more physically impaired, and younger patients with advanced cancer were more likely to meet criteria for an anxiety disorder. Patients with advanced cancer who had an anxiety disorder were more likely to experience greater challenges to the physician-patient relationship. Cancer 2010;116:1810-9. (C) 2010 American Cancer Society C1 [Spencer, Ryan] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Med, Boston, MA 02115 USA. [Nilsson, Matthew; Wright, Alexi; Prigerson, Holly] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Wright, Alexi] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pirl, William] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Spencer, R (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Med, 75 Francis St,ASB 3, Boston, MA 02115 USA. EM rjspencer@partners.org FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA 106,370]; Dana-Farber/Harvard Cancer Center [U56CA118641, P30CA0651]; Center for Psycho-Oncology and Palliative Care Research at Dana-Farber Cancer Institute FX Supported in part by the following grants to Dr. Prigerson: MH63892 from the National Institute of Mental Health and CA 106,370 from the National Cancer Institute, Dana-Farber/Harvard Cancer Center U56CA118641 and P30CA0651 pilot grants, and the Center for Psycho-Oncology and Palliative Care Research at Dana-Farber Cancer Institute. NR 36 TC 27 Z9 27 U1 2 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2010 VL 116 IS 7 BP 1810 EP 1819 DI 10.1002/cncr.24954 PG 10 WC Oncology SC Oncology GA 574IV UT WOS:000275983500025 PM 20187099 ER PT J AU Prabhakar, S Brenner, GJ Sung, B Messerli, SM Mao, J Sena-Esteves, M Stemmer-Rachamimov, A Tannous, B Breakefield, XO AF Prabhakar, S. Brenner, G. J. Sung, B. Messerli, S. M. Mao, J. Sena-Esteves, M. Stemmer-Rachamimov, A. Tannous, B. Breakefield, X. O. TI Imaging and therapy of experimental schwannomas using HSV amplicon vector-encoding apoptotic protein under Schwann cell promoter SO CANCER GENE THERAPY LA English DT Article DE neurofibromatosis type 2; bioluminescence imaging; caspase-1; virus vectors; tumors ID HERPES-SIMPLEX-VIRUS; MEDIATED GENE-TRANSFER; MUTANT NF2 PROTEIN; IN-VIVO; NEUROFIBROMATOSIS TYPE-2; PHASE-I; VESTIBULAR SCHWANNOMA; FLUORESCENT PROTEIN; NEURAL CELLS; MOUSE AB Schwannomas are benign tumors forming along peripheral nerves that can cause deafness, pain and paralysis. Current treatment involves surgical resection, which can damage associated nerves. To achieve tumor regression without damage to nerve fibers, we generated an HSV amplicon vector in which the apoptosis-inducing enzyme, caspase-1 (ICE), was placed under the Schwann cell-specific P0 promoter. Infection of schwannoma, neuroblastoma and fibroblastic cells in culture with ICE under the P0 promoter showed selective toxicity to schwannoma cells, while ICE under a constitutive promoter was toxic to all cell types. After direct intratumoral injection of the P0-ICE amplicon vector, we achieved marked regression of schwannoma tumors in an experimental xenograft mouse model. Injection of this amplicon vector into the sciatic nerve produced no apparent injury to the associated dorsal root ganglia neurons or myelinated nerve fibers. The P0-ICE amplicon vector provides a potential means of 'knifeless resection' of schwannoma tumors by injection of the vector into the tumor with low risk of damage to associated nerve fibers. Cancer Gene Therapy (2010) 17, 266-274; doi: 10.1038/cgt.2009.71; published online 16 October 2009 C1 [Prabhakar, S.; Brenner, G. J.; Sung, B.; Messerli, S. M.; Mao, J.; Sena-Esteves, M.; Stemmer-Rachamimov, A.; Tannous, B.; Breakefield, X. O.] Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. [Prabhakar, S.; Messerli, S. M.; Sena-Esteves, M.; Tannous, B.; Breakefield, X. O.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. [Prabhakar, S.; Messerli, S. M.; Sena-Esteves, M.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Brenner, G. J.] Massachusetts Gen Hosp, Dept Anaesthesiol, Boston, MA 02114 USA. [Sung, B.; Mao, J.] Massachusetts Gen Hosp, Pain Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Stemmer-Rachamimov, A.; Breakefield, X. O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tannous, B.; Breakefield, X. O.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02114 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, Bldg 149,13th St,6th Floor, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu FU NINDS [NS024279]; Department of the Army, US Army Research Medical Research and Material Command [W81XWH-04-1-0237]; NCRR [P41 RR001395]; Terrill Family and Texas Neurofibromatosis Foundation FX We thank Ms. Suzanne McDavitt for skilled editorial assistance. This work was supported by grants from NINDS NS024279, Department of the Army, US Army Research Medical Research and Material Command Award W81XWH-04-1-0237, the P41 RR001395 NCRR grant, the Terrill Family and Texas Neurofibromatosis Foundation. NR 44 TC 8 Z9 8 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD APR PY 2010 VL 17 IS 4 BP 266 EP 274 DI 10.1038/cgt.2009.71 PG 9 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 570TJ UT WOS:000275700700005 PM 19834516 ER PT J AU Rech, AJ Mick, R Kaplan, DE Chang, KM Domchek, SM Vonderheide, RH AF Rech, Andrew J. Mick, Rosemarie Kaplan, David E. Chang, Kyong-Mi Domchek, Susan M. Vonderheide, Robert H. TI Homeostasis of peripheral FoxP3(+) CD4(+) regulatory T cells in patients with early and late stage breast cancer SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Breast cancer; Regulatory T cell; Clinical trial ID TUMOR-IMMUNITY; IN-VIVO; ANTITUMOR IMMUNITY; EXPRESSION; DEPLETION; MELANOMA; INDUCTION; RESPONSES; BLOOD; RECRUITMENT AB FoxP3 (+) CD4 (+) regulatory T cells (Tregs) are important mediators of peripheral immune tolerance, acting via multiple mechanisms to suppress cellular immunity including antitumor responses. Although therapeutic strategies have been proposed to deplete Tregs in patients with breast cancer and other malignancies, dynamic changes in the Treg compartment as a function of stage and treatment of breast cancer remain poorly understood. Here, we evaluated peripheral blood CD4(+) T cells and FoxP3(+) CD4(+) T cells from 45 patients with early or late stage breast cancer and compared percentages, absolute counts, and Treg function to those from healthy volunteers (HV) of comparable age. Patients having completed adjuvant chemotherapy and patients with metastatic cancer exhibited significantly lower absolute CD4 counts and significantly higher percentages of FoxP3(+) CD4(+) T cells. In contrast, the absolute counts of circulating FoxP3(+) CD4(+) T cells did not differ significantly among early stage patients, late stage patients, or HV. Functionally, FoxP3(+) CD4(+) T cells from all donor groups similarly expressed CTLA-4 and failed to secrete IFN-gamma in response to stimulation. Thus, although Tregs comprise an increased percentage of circulating CD4(+) T cells in patients with metastatic breast cancer and patients in remission after completing the adjuvant chemotherapy, the systemic Treg pool, as measured by absolute counts, appears relatively constant regardless of disease stage or treatment status. Total CD4(+) T cell counts are not constant, however, suggesting that homeostatic mechanisms, or susceptibility to cytotoxic or malignant insults, fundamentally differ for regulatory and non-regulatory CD4(+) T cells. C1 [Rech, Andrew J.; Vonderheide, Robert H.] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Mick, Rosemarie] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Kaplan, David E.; Chang, Kyong-Mi] Univ Penn, Sch Med, Div Gastroenterol, Dept Med, Philadelphia, PA 19104 USA. [Kaplan, David E.; Chang, Kyong-Mi] Philadelphia Vet Affairs Med Ctr, Gastroenterol Sect, Philadelphia, PA USA. [Domchek, Susan M.] Univ Penn, Sch Med, Abramson Canc Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA. RP Vonderheide, RH (reprint author), Univ Penn, Sch Med, Abramson Family Canc Res Inst, 551 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM rhv@exchange.upenn.edu OI Kaplan, David E./0000-0002-3839-336X FU Breast Cancer Research Foundation; NCI [R01 CA111377] FX We thank Theresa Colligon and Adrianna Recio, RN, and Drs. Daniel J. Powell, Jr., Tatiana Golovina, and James Riley for helpful discussions. This study was supported by grants from the Breast Cancer Research Foundation and the NCI (R01 CA111377) and a gift from Mark and Paula Solomon. NR 44 TC 27 Z9 28 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD APR PY 2010 VL 59 IS 4 BP 599 EP 607 DI 10.1007/s00262-009-0780-x PG 9 WC Oncology; Immunology SC Oncology; Immunology GA 549XH UT WOS:000274087300010 PM 19855964 ER PT J AU Wong, KK Jacks, T Dranoff, G AF Wong, Kwok-Kin Jacks, Tyler Dranoff, Glenn TI NF-KB Fans the Flames of Lung Carcinogenesis SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID T-CELLS; KAPPA-B; MOUSE MODEL; IKK-BETA; CANCER; INFLAMMATION; IMMUNITY; TUMORS; TUMORIGENESIS; INTERFERONS AB This perspective on Deng et al. (beginning on p. 424 in this issue of the journal) examines the link between NF-kappa B and lung tumorigenesis. Experiments in genetically engineered mouse models of lung cancers are elucidating protumorigenic roles of NF-kappa B activation in lung cancer pathogenesis. Our growing understanding of the tumor-promoting NF-kappa B downstream effector pathways could lead to the development of novel approaches for lung cancer therapy and chemoprevention. Cancer Prev Res; 3(4); 403-5. (C)2010 AACR. C1 [Wong, Kwok-Kin; Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wong, Kwok-Kin; Dranoff, Glenn] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Jacks, Tyler] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Wong, KK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana Bldg 810B, Boston, MA 02115 USA. EM Kwong1@partners.org OI wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [R01 CA140594, R01 CA122794-04, R01 CA122794, R01 CA140594-01]; NIA NIH HHS [R01 AG027757, R01 AG027757-04] NR 33 TC 13 Z9 13 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD APR PY 2010 VL 3 IS 4 BP 403 EP 405 DI 10.1158/1940-6207.CAPR-10-0042 PG 3 WC Oncology SC Oncology GA 577ZS UT WOS:000276263600003 PM 20354166 ER PT J AU Dineen, SP Roland, CL Greer, R Carbon, JG Toombs, JE Gupta, P Bardeesy, N Sun, HZ Williams, N Minna, JD Brekken, RA AF Dineen, Sean P. Roland, Christina L. Greer, Rachel Carbon, Juliet G. Toombs, Jason E. Gupta, Puja Bardeesy, Nabeel Sun, Haizhou Williams, Noelle Minna, John D. Brekken, Rolf A. TI Smac Mimetic Increases Chemotherapy Response and Improves Survival in Mice with Pancreatic Cancer SO CANCER RESEARCH LA English DT Article ID ALPHA-DEPENDENT APOPTOSIS; X-LINKED INHIBITOR; TNF-ALPHA; DUCTAL ADENOCARCINOMA; IN-VIVO; XIAP; CELLS; ANTAGONISTS; RESISTANCE; PROTEIN AB Failure of chemotherapy in the treatment of pancreatic cancer is often due to resistance to therapy-induced apoptosis. A major mechanism for such resistance is the expression and activity of inhibitors of apoptosis proteins (IAP). Smac (second mitochondria-derived activator of caspase) is a mitochondrial protein that inhibits IAPs. We show that JP1201, a Smac mimetic, is a potent enhancer of chemotherapy in robust mouse models of pancreatic cancer. Combination of JP1201 with gemcitabine reduced primary and metastatic tumor burden in orthotopic xenograft and syngenic tumor models, induced regression of established tumors, and prolonged survival in xenograft and transgenic models of pancreatic cancer. The effect of JP1201 was phenocopied by XIAP small interfering RNA in vitro and correlated with elevated levels of tumor necrosis factor alpha protein in vivo. The continued development of JP1201 and other strategies designed to enhance therapy-induced apoptosis in pancreatic cancer is warranted. Cancer Res; 70(7); 2852-61. (C) 2010 AACR. C1 [Dineen, Sean P.; Roland, Christina L.; Carbon, Juliet G.; Toombs, Jason E.; Brekken, Rolf A.] Univ Texas SW Med Sch, Dept Surg, Div Surg Oncol, Dallas, TX USA. [Dineen, Sean P.; Roland, Christina L.; Greer, Rachel; Carbon, Juliet G.; Toombs, Jason E.; Gupta, Puja; Minna, John D.; Brekken, Rolf A.] Univ Texas SW Med Sch, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. [Gupta, Puja] Univ Texas SW Med Sch, Dept Pediat, Dallas, TX USA. [Williams, Noelle] Univ Texas SW Med Sch, Dept Biochem, Dallas, TX USA. [Minna, John D.] Univ Texas SW Med Sch, Dept Internal Med, Dallas, TX USA. [Minna, John D.; Brekken, Rolf A.] Univ Texas SW Med Sch, Dept Pharmacol, Dallas, TX USA. [Sun, Haizhou] Joyant Pharmaceut, Dallas, TX USA. [Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Brekken, RA (reprint author), Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, 6000 Harry Hines Blvd, Dallas, TX 75390 USA. EM rolf.brekken@utsouthwestern.edu RI Dineen, Sean/B-6222-2013; Dineen, Sean/M-3741-2013; Dineen, Sean/K-1471-2015 OI Dineen, Sean/0000-0002-2012-2238 FU Joyant Pharmaceuticals; Effie Marie Cain Scholarship in Angiogenesis Research; Susan G. Komen for the Cure; UT SPORE in Lung Cancer [P50 CA070907] FX A sponsored research agreement from Joyant Pharmaceuticals (R. A. Brekken), Effie Marie Cain Scholarship in Angiogenesis Research (R. A. Brekken), a post-doctoral fellowship from Susan G. Komen for the Cure (S. P. Dineen), and the UT SPORE in Lung Cancer (P50 CA070907, J.D. Minna). NR 30 TC 60 Z9 64 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2010 VL 70 IS 7 BP 2852 EP 2861 DI 10.1158/0008-5472.CAN-09-3892 PG 10 WC Oncology SC Oncology GA 607GB UT WOS:000278486000030 PM 20332237 ER PT J AU Yang, C Ji, D Weinstein, EJ Choy, E Hornicek, FJ Wood, KB Liu, XZ Mankin, H Duan, ZF AF Yang, Cao Ji, Diana Weinstein, Edward J. Choy, Edwin Hornicek, Francis J. Wood, Kirkham B. Liu, Xianzhe Mankin, Henry Duan, Zhenfeng TI The kinase Mirk is a potential therapeutic target in osteosarcoma SO CARCINOGENESIS LA English DT Article ID MEDIATES CELL-SURVIVAL; COLON-CANCER CELLS; FACTOR-I RECEPTOR; MIRK/DYRK1B; INHIBITION; RESISTANCE; APOPTOSIS; SCREEN; GROWTH; RHABDOMYOSARCOMA AB Osteosarcoma is the most common primary malignant bone tumor affecting children and adolescents. The majority of patients are treated by surgery and chemotherapy but have limited alternative therapeutic options. Kinases play an important role in the growth and survival of tumor cells. We aim to identify specific kinases to be vital in the survival of osteosarcoma cells and thus may be a key target in creating novel anticancer therapies. A lentiviral short hairpin RNA kinase library, screened osteosarcoma cells, identified kinase minibrain-related kinase (Mirk) (Dyrk1B) as a potential target. Knockdown Mirk expression could inhibit cell growth and induce apoptosis. Chemically synthetic small interfering RNA knockdown and complementary DNA rescue assay further confirmed the results from the decrease of Mirk gene expression. The relationship between Mirk gene expression and the clinical characteristics of patients with osteosarcoma was investigated using tissue microarray and immunohistochemistry analysis. The data indicate that the overall survival rate of patients with Mirk high staining (high levels of Mirk protein expression) is significantly shorter than those with Mirk low staining and moderate staining. This highlights Mirk's potential to serve as a promising target for molecular therapy in the treatment of osteosarcoma. C1 [Yang, Cao; Hornicek, Francis J.; Wood, Kirkham B.; Liu, Xianzhe; Mankin, Henry; Duan, Zhenfeng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. [Yang, Cao; Choy, Edwin; Hornicek, Francis J.; Liu, Xianzhe; Mankin, Henry; Duan, Zhenfeng] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Yang, Cao; Liu, Xianzhe] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Orthopaed Surg, Union Hosp, Wuhan 430022, Peoples R China. [Ji, Diana; Weinstein, Edward J.] Sigma Aldrich Biotechnol, Sigma Adv Genet Engn Labs, St Louis, MO 63146 USA. RP Duan, ZF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. EM zduan@partners.org OI Choy, Edwin/0000-0001-9896-8084 FU Gattegno and Wechsler funds; National Cancer Institute, National Institutes of Health; Sarcoma Foundation of America FX Gattegno and Wechsler funds; National Cancer Institute, National Institutes of Health (Nanotechnology Platform) to Z.D.; Sarcoma Foundation of America. NR 34 TC 26 Z9 27 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2010 VL 31 IS 4 BP 552 EP 558 DI 10.1093/carcin/bgp330 PG 7 WC Oncology SC Oncology GA 578HV UT WOS:000276285200003 PM 20042639 ER PT J AU Ahmad, I Yeddula, K Wicky, S Kalva, SP AF Ahmad, Iftikhar Yeddula, Kalpana Wicky, Stephan Kalva, Sanjeeva P. TI Clinical Sequelae of Thrombus in an Inferior Vena Cava Filter SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Inferior vena cava filter; Pulmonary embolism; Deep venous thrombosis; Filter thrombus ID PULMONARY-EMBOLISM; VENOUS THROMBOEMBOLISM; PLACEMENT; PREVENTION; EXPERIENCE; OCCLUSION AB The purpose of this study was to assess the long-term clinical sequelae of inferior vena cava (IVC) filter thrombus and the effect of anticoagulation on filter thrombus. Of 1,718 patients who had IVC filters placed during 2001-2008, 598 (34.8%) had follow-up abdominal CT. Filter thrombus was seen in 111 of the 598 (18.6%). There were 44 men (39.6%). The mean age at filter placement was 64 years. The medical diseases included cancer in 64, trauma in 15, stroke in 12, and others in 20. The frequency of filter thrombus on CT and asymptomatic filter thrombus on CT was calculated. The frequency of pulmonary embolism (PE) in patients with filter thrombus was calculated. The frequency of thrombus progression or regression (on CT, available in 56) was calculated. The effect of anticoagulation on filter thrombus regression/progression was evaluated using the Fisher exact test by comparing the group of patients who received anticoagulants versus those who did not. A P-value of < 0.05 was considered significant. The overall frequency of filter thrombus was 18.6%. Total occlusion of the IVC filter was seen in 12 of 598 (2%). The filter thrombus was asymptomatic in 110 (18.3%). Filter thrombus was detected after a median of 35 days (range, 0-2082) following filter placement. Thrombus extended above the filter in 4 (3.6%); IVC thrombus below the filter was seen in 35(31.5%). Thrombus in the filter occluded < 25% of the filter volume in 58 (52.3%), 25-50% in 21 (18.9%), and 50-75% in 20 (18%). Total IVC occlusion was seen in 12 (10.8%). Eighty-three patients received anticoagulation. Sixteen patients developed symptoms of PE. PE was confirmed on CT in 3 of 15 (2.7%). On follow-up, filter thrombus regressed completely in 19 (33.9%) after a median of 6 months. Filter thrombus decreased in size in 13 (23.2%) and it progressed without IVC occlusion in 7 (12.6%). In one (1.7%), filter thrombus progressed to IVC occlusion. Filter thrombus remained stable in 16 (28.6%). There was no significant difference in thrombus regression or progression rates whether or not the patients received anticoagulation for filter thrombus. In conclusion, asymptomatic thrombus in the filter is common and it rarely progresses to complete caval occlusion. Anticoagulation has little effect on the resolution of filter thrombosis and future occurrence of PE. C1 [Ahmad, Iftikhar; Yeddula, Kalpana; Wicky, Stephan; Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ahmad, Iftikhar; Yeddula, Kalpana; Wicky, Stephan; Kalva, Sanjeeva P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB 297,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 21 TC 31 Z9 32 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD APR PY 2010 VL 33 IS 2 BP 285 EP 289 DI 10.1007/s00270-009-9664-x PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 571JG UT WOS:000275747500007 PM 19688372 ER PT J AU Wilk, KE Macrina, LC Reinold, MM AF Wilk, Kevin E. Macrina, Leonard C. Reinold, Michael M. TI Rehabilitation following Microfracture of the Knee SO CARTILAGE LA English DT Article DE knee; rehabilitation; microfracture; arthroscopy AB Postoperative rehabilitation programs following articular cartilage repair procedures will vary greatly among patients and need to be individualized based on the nature of the lesion, the unique characteristics of the patient, and the type and detail of each surgical procedure. These programs are based on knowledge of the basic science, anatomy, and biomechanics of articular cartilage as well as the biological course of healing following surgery. The goal is to restore full function in each patient as quickly as possible by facilitating a healing response without overloading the healing articular cartilage. The purpose of this article is to overview the principles of rehabilitation following microfracture procedures of the knee. C1 [Wilk, Kevin E.; Macrina, Leonard C.] Amer Sports Med Inst, Champ Sports Med, Birmingham, AL 35205 USA. [Reinold, Michael M.] Boston Red Sox, Boston, MA USA. [Reinold, Michael M.] Massachusetts Gen Hosp, Dept Orthoped Surg, Div Sports Med, Boston, MA 02114 USA. RP Macrina, LC (reprint author), Amer Sports Med Inst, Champ Sports Med, 805 St Vincents Dr,Suite G100, Birmingham, AL 35205 USA. EM lenmac08@yahoo.com NR 61 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1947-6035 EI 1947-6043 J9 CARTILAGE JI Cartilage PD APR PY 2010 VL 1 IS 2 BP 96 EP 107 DI 10.1177/1947603510366029 PG 12 WC Orthopedics SC Orthopedics GA V36MW UT WOS:000209216900004 PM 26069540 ER PT J AU Mithoefer, K Gill, TJ Cole, BJ Williams, RJ Mandelbaum, BR AF Mithoefer, Kai Gill, Thomas J. Cole, Brian J. Williams, Riley J. Mandelbaum, Bert R. TI Clinical Outcome and Return to Competition after Microfracture in the Athlete's Knee:An Evidence-Based Systematic Review SO CARTILAGE LA English DT Article DE sport; athletics; cartilage; microfracture; injury; repair AB Microfracture is frequently used for articular cartilage repair in athletes. This study aimed to define the strength and weaknesses of this minimally invasive cartilage repair technique in the athletic population in an effort to optimize indications, functional outcome, and athletic participation after microfracture in the athlete's knee. A systematic analysis of original studies using microfracture in athletes was performed. Functional outcome was assessed by activity outcome scores, ability to return to sports participation, timing of the return to sport, level of postoperative sports activity, and continuation of athletic competition over time. Thirteen studies describing 821 athletes were included in the analysis with an average follow-up of 42 months. Good or excellent results were reported in 67% of athletes with normal International Knee Documentation Committee (IKDC) scores in 80% and significant increase of Lysholm scores, Tegner activity scores, and Knee injury and Osteoarthritis Outcome Score (KOOS) sports subscales. Return to sports was achieved in 66% at an average of 8 months after surgery, with return to competition at the preinjury level in 67%. Forty-nine percent of athletes continued to compete without change in level of play, while decreasing function was observed in 42% after 2 to 5 years. Athlete's age, preoperative duration of symptoms, level of play, lesion size, and repair tissue morphology affected sports activity after microfracture. Microfracture improves knee function and frequently allows for return to sports at the preinjury level, but deterioration of athletic function occurs in some patients. Several independent factors were identified that can help to optimize the return to athletic competition after microfracture in the athlete's knee. C1 [Mithoefer, Kai] Harvard Univ, Sch Med, Harvard Vanguard Orthoped & Sports Med, Chestnut Hill, MA 02467 USA. [Gill, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cole, Brian J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Williams, Riley J.] Hosp Special Surg, New York, NY 10021 USA. [Mandelbaum, Bert R.] Santa Monica Orthoped & Sports Med Fdn, Los Angeles, CA USA. RP Mithoefer, K (reprint author), Harvard Univ, Sch Med, Harvard Vanguard Orthoped & Sports Med, 291 Independence Dr, Chestnut Hill, MA 02467 USA. EM kmithoefer@partners.org NR 41 TC 13 Z9 13 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1947-6035 EI 1947-6043 J9 CARTILAGE JI Cartilage PD APR PY 2010 VL 1 IS 2 BP 113 EP 120 DI 10.1177/1947603510366576 PG 8 WC Orthopedics SC Orthopedics GA V36MW UT WOS:000209216900006 PM 26069542 ER PT J AU Dave, B Sharma, A Kwolek, C DeMoya, M Wicky, S Kalva, S AF Dave, Bhavika Sharma, Ashish Kwolek, Christopher DeMoya, Mark Wicky, Stephan Kalva, Sanjeeva TI Percutaneous Transcatheter Arterial Embolization of Inferior Pancreatico-Duodenal Artery Aneurysms Associated with Celiac Artery Stenosis or Occlusion SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE EMBO; embolization; IMAG; imaging (CT/MR); OCCL; total occlusions ID MEDIAN ARCUATE LIGAMENT; AXIS STENOSIS; ENDOVASCULAR MANAGEMENT; COIL EMBOLIZATION; TRUNK OCCLUSION; COMPRESSION; PSEUDOANEURYSMS; PATIENT; CT AB Objectives: To report our experience with percutaneous TAE of true IPDA aneurysms. Background: Most IPDA aneurysms are ruptured at presentation causing a high mortality risk. Minimally invasive treatment approaches may improve overall outcomes in such patients. Methods: Between 1996 and 2007, seven patients (5 Males; mean age 55y) with symptomatic IPDA aneurysms and severe degree (>75%) celiac artery stenosis were treated with percutaneous TAE. The medical and imaging records were reviewed for demographics, clinical presentation, treatment, complications and follow-up. Patients presented with epigastric pain (7/7), hemodynamic shock (2/7) and rectal bleeding (2/7). Selective catheter angiography was performed in all patients with the intent to embolize the aneurysms. Results: A total of nine aneurysms were seen in seven patients. Two patients had two aneurysms each. The aneurysms ranged in size from 0.5 to 4.0 cm (mean 1.9 cm). Trans-catheter coil embolization was successful in 8/9 (89%) aneurysms in 6 patients. Following unsuccessful TAE of one aneurysm in one of the patient, the aneurysm was treated successfully with direct CT-guided percutaneous transabdominal injection of N-butyl-2-cyanoacrylate. There were no complications on follow up. Angioplasty and stenting of the celiac artery were performed in one patient for complete occlusion. None of the patients developed clinical or imaging evidence of visceral ischemia following embolization. None had recurrent symptoms during clinical follow-up (median 3 years, range 0.5-13.5 years). Follow-up CT (Median 6.6 months, range 4 days-11.5 years) in all patients showed no recurrence of the aneurysm. Conclusion: IPDA aneurysms associated with celiac axis stenosis can be successfully treated with percutaneous embolization with minimal recurrence. (C) 2010 Wiley-Liss, Inc. C1 [Dave, Bhavika] Univ Mississippi, Med Ctr, Dept Radiol, Jackson, MS 39216 USA. [Sharma, Ashish; Wicky, Stephan; Kalva, Sanjeeva] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kwolek, Christopher; DeMoya, Mark] Massachusetts Gen Hosp, Dept Vasc Surg, Boston, MA 02114 USA. RP Dave, B (reprint author), Univ Mississippi, Med Ctr, Dept Radiol, 2500 N State St, Jackson, MS 39216 USA. EM bhavikadave@msn.com NR 41 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD APR 1 PY 2010 VL 75 IS 5 BP 663 EP 672 DI 10.1002/ccd.22395 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 582IC UT WOS:000276589300005 PM 20155804 ER PT J AU Sharma, SV Lee, DY Li, BH Quinlan, MP Takahashi, F Maheswaran, S McDermott, U Azizian, N Zou, L Fischbach, MA Wong, KK Brandstetter, K Wittner, B Ramaswamy, S Classon, M Settleman, J AF Sharma, Sreenath V. Lee, Diana Y. Li, Bihua Quinlan, Margaret P. Takahashi, Fumiyuki Maheswaran, Shyamala McDermott, Ultan Azizian, Nancy Zou, Lee Fischbach, Michael A. Wong, Kwok-Kin Brandstetter, Kathleyn Wittner, Ben Ramaswamy, Sridhar Classon, Marie Settleman, Jeff TI A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations SO CELL LA English DT Article ID STEM-CELLS; THERAPEUTIC RESISTANCE; HISTONE MODIFICATION; GROWTH; INSULIN; MECHANISMS; SENSITIVITY; RETREATMENT; INHIBITORS; DISEASE AB Accumulating evidence implicates heterogeneity within cancer cell populations in the response to stressful exposures, including drug treatments. While modeling the acute response to various anticancer agents in drug-sensitive human tumor cell lines, we consistently detected a small subpopulation of reversibly "drug-tolerant" cells. These cells demonstrate >100-fold reduced drug sensitivity and maintain viability via engagement of IGF-1 receptor signaling and an altered chromatin state that requires the histone demethylase RBP2/KDM5A/Jarid1A. This drug-tolerant phenotype is transiently acquired and relinquished at low frequency by individual cells within the population, implicating the dynamic regulation of phenotypic heterogeneity in drug tolerance. The drug-tolerant subpopulation can be selectively ablated by treatment with IGF-1 receptor inhibitors or chromatin-modifying agents, potentially yielding a therapeutic opportunity. Together, these findings suggest that cancer cell populations employ a dynamic survival strategy in which individual cells transiently assume a reversibly drug-tolerant state to protect the population from eradication by potentially lethal exposures. C1 [Sharma, Sreenath V.; Lee, Diana Y.; Li, Bihua; Quinlan, Margaret P.; Takahashi, Fumiyuki; Maheswaran, Shyamala; McDermott, Ultan; Azizian, Nancy; Zou, Lee; Fischbach, Michael A.; Wittner, Ben; Ramaswamy, Sridhar; Classon, Marie; Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Wong, Kwok-Kin; Brandstetter, Kathleyn] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Classon, M (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM classon@helix.mgh.harvard.edu; settleman@helix.mgh.harvard.edu OI McDermott, Ultan/0000-0001-9032-4700; wong, kwok kin/0000-0001-6323-235X FU LUNGevity Foundation; Goldman Philanthropic; NIH [RO1CA115830, P20 CA090578] FX We thank the members of the Settleman laboratory, Luisa Di Stefano, Daniel Haber, and Kurt Isselbacher for helpful discussions through the course of these studies. We also thank Lisa Drew and Jeff Hanke (AstraZeneca) for providing AZ628; James Christensen (Pfizer) for providing PF-2341066; Robert Schlegel (Novartis) for providing AEW541; Jeff Engelman for providing the drug-resistant HCC827 cells; and Toshi Shioda for providing shRNA plasmids and performing gene expression array analysis. This work was supported by an award from the LUNGevity Foundation and Goldman Philanthropic Partnerships to S. V. S. and NIH RO1CA115830 and NIH P20 CA090578 to J. S. NR 42 TC 711 Z9 720 U1 6 U2 62 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 1 PY 2010 VL 141 IS 1 BP 69 EP 80 DI 10.1016/j.cell.2010.02.027 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 577GS UT WOS:000276211100013 PM 20371346 ER PT J AU Kharas, MG Gritsman, K AF Kharas, Michael G. Gritsman, Kira TI Akt A double-edged sword for hematopoietic stem cells SO CELL CYCLE LA English DT Editorial Material DE Akt; leukemia; HSC; Pten; T-ALL; PI3 kinase ID ACUTE MYELOID-LEUKEMIA; PROGENITORS C1 [Kharas, Michael G.; Gritsman, Kira] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kharas, Michael G.; Gritsman, Kira] Harvard Univ, Sch Med, Boston, MA USA. [Gritsman, Kira] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gritsman, K (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM kgritsman@partners.org FU NCI NIH HHS [T32 CA009172] NR 11 TC 7 Z9 7 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2010 VL 9 IS 7 BP 1223 EP 1224 PG 2 WC Cell Biology SC Cell Biology GA 579KO UT WOS:000276369300002 PM 20234178 ER PT J AU Odajima, J Kalaszczynska, I Sicinski, P AF Odajima, Junko Kalaszczynska, Ilona Sicinski, Piotr TI Cyclins A and E trigger DNA damage SO CELL CYCLE LA English DT News Item ID MAMMALIAN-CELLS; REPLICATION; CANCER C1 [Odajima, Junko] Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Odajima, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM Peter_sicinski@dfci.harvard.edu FU NCI NIH HHS [R01 CA132740] NR 14 TC 3 Z9 3 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2010 VL 9 IS 7 BP 1231 EP 1232 PG 2 WC Cell Biology SC Cell Biology GA 579KO UT WOS:000276369300006 PM 20404525 ER PT J AU Huang, Y Yang, X Wu, Y Jing, W Cai, X Tang, W Liu, L Liu, Y Grottkau, BE Lin, Y AF Huang, Y. Yang, X. Wu, Y. Jing, W. Cai, X. Tang, W. Liu, L. Liu, Y. Grottkau, B. E. Lin, Y. TI gamma-secretase inhibitor induces adipogenesis of adipose-derived stem cells by regulation of Notch and PPAR-gamma SO CELL PROLIFERATION LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; SIGNALING PATHWAY; TRANSCRIPTION FACTOR; DIFFERENTIATION; EXPRESSION; PREF-1; PROLIFERATION; PREADIPOCYTES; SPECIFICATION; TARGET AB Objective: To determine the inhibitory effect and mechanism of Notch signalling on adipogenesis of mouse adipose-derived stem cells (mASCs). Materials and methods: Varied concentrations of N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester (DAPT) were added to mASCs 3 days before adipogenic induction with insulin-containing differentiation medium. The process of adipogenesis and ability of lipid droplet accumulation were analysed using oil red-O staining. The Notch signalling pathway (Notch-1, -2, -3, -4, Hes-1 and Hey-1) and adipogenesis-related factors (PPAR-gamma, DLK-1/Pref-1 and Acrp) were tested using real-time PCR, Western blot analysis and immunofluorescence staining assays. Results: We demonstrated that Notch-2-Hes-1 signalling pathway was inhibited dose-dependently by DAPT in mASCs. In addition, transcription of PPAR-gamma was promoted by DAPT before adipogenic induction, while inhibitor of adipogenesis DLK-1/Pref-1 was further depressed. At early stages of differentiation (2-4 days), adipogenesis in mASCs was advanced and significantly enhanced in 5 and 10 mu m DAPT pre-treated cases. On day 4, in differentiated mASCs cases with DAPT pre-treatment, we also found promotion of activation of de-PPAR-gamma and depression of HES-1, DLK-1/Pref-1 mRNA and protein expression. Conclusions: We conclude that blocking Notch signalling with DAPT enhances adipogenesis of differentiated mASCs at an early stage. It may be due to depression of DLK-1/Pref-1 and promotion of de-PPAR-gamma activation, which work through inhibition of Notch-2-Hes-1 pathway by DAPT. C1 [Grottkau, B. E.; Lin, Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Children & Pediat Orthopaed L, Boston, MA USA. [Huang, Y.; Yang, X.; Wu, Y.; Jing, W.; Cai, X.; Tang, W.; Liu, L.; Liu, Y.; Lin, Y.] Sichuan Univ, State Key Lab Oral Dis, W China Coll Stomatol, Chengdu 610064, Peoples R China. [Huang, Y.] Capital Med Univ, Beijing Friendship Hosp, Dept Oral & Maxillofacial Surg, Beijing, Peoples R China. RP Grottkau, BE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed,Children & Pediat Orthopaed Lab Ti, Boston, MA 02115 USA. EM bgrottkau@partners.org; yunfenglin@scu.edu.cn RI liu, lei/B-2263-2012; Lin, Yunfeng/M-5438-2013; Lin, Yunfeng/H-3393-2011; OI Lin, Yunfeng/0000-0003-1224-6561; Lin, Yunfeng/0000-0003-1224-6561; Cai, Xiaoxiao/0000-0002-5654-7414 FU National Natural Science Foundation of China [30801304]; Anthony and Constance Franchi Fund for Pediatric Orthopaedics at the MassGeneral Hospital for Children; Specialized Research Fund for the Doctoral Program of Higher Education [20070610062]; State Key Laboratory of Oral Diseases, Sichuan University [SKLOD011]; Applied Fundamental Project of Sichuan Province [2008JY0028-2] FX This study was funded by the National Natural Science Foundation of China (30801304), the Anthony and Constance Franchi Fund for Pediatric Orthopaedics at the MassGeneral Hospital for Children, Specialized Research Fund for the Doctoral Program of Higher Education (20070610062), Opening Funding of the State Key Laboratory of Oral Diseases, Sichuan University (SKLOD011) and Applied Fundamental Project of Sichuan Province (2008JY0028-2). NR 49 TC 31 Z9 34 U1 1 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0960-7722 J9 CELL PROLIFERAT JI Cell Prolif. PD APR PY 2010 VL 43 IS 2 BP 147 EP 156 DI 10.1111/j.1365-2184.2009.00661.x PG 10 WC Cell Biology SC Cell Biology GA 560VR UT WOS:000274932500006 PM 20447060 ER PT J AU Platt, AB Localio, AR Brensinger, CM Cruess, DG Christie, JD Gross, R Parker, CS Price, M Metlay, JP Cohen, A Newcomb, CW Strom, BL Laskin, MS Kimmel, SE AF Platt, Alec B. Localio, A. Russell Brensinger, Colleen M. Cruess, Dean G. Christie, Jason D. Gross, Robert Parker, Catherine S. Price, Maureen Metlay, Joshua P. Cohen, Abigail Newcomb, Craig W. Strom, Brian L. Laskin, Mitchell S. Kimmel, Stephen E. TI Can We Predict Daily Adherence to Warfarin? Results From the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study SO CHEST LA English DT Article ID ORAL ANTICOAGULANT TREATMENT; ATRIAL-FIBRILLATION; INCEPTION-COHORT; RISK-FACTORS; MANAGEMENT; REGRESSION; THERAPY; RULES; NONADHERENCE; OUTCOMES AB Background: Warfarin is the primary therapy to prevent stroke and venous thromboembolism. Significant periods of nonadherence frequently go unreported by patients and undetected by providers. Currently, no comprehensive screening tool exists to help providers assess the risk of nonadherence at the time of initiation of warfarin therapy. Methods: This article reports on a prospective cohort study of adults initiating warfarin therapy at two anticoagulation clinics (university- and Veterans Affairs-affiliated). Nonadherence, defined by failure to record a correct daily pill bottle opening, was measured daily by electronic pill cap monitoring. A multivariable logistic regression model was used to develop a point system to predict daily nonadherence to warfarin. Results: We followed 114 subjects for a median of 141 days. Median nonadherence of the participants was 14.4% (interquartile range [IQR], 5.8-33.8). A point system, based on nine demographic, clinical, and psychosocial factors, distinguished those demonstrating low vs high levels of nonadherence: four points or fewer, median nonadherence 5.8% (IQR, 2.3-14.1); five points, 9.1% (IQR, 5.9-28.6); six points, 14.5% (IQR, 7.1-24.1); seven points, 14.7% (IQR, 7.0-34.7); and eight points or more, 29.3% (IQR, 15.5-41.9). The model produces a c-statistic of 0.66 (95% CI, 0.61-0.71), suggesting modest discriminating ability to predict day-level warfarin nonadherence. Conclusions: Poor adherence to warfarin is common. A screening tool based on nine demographic, clinical, and psychosocial factors, if further validated in other patient populations, may help to identify groups of patients at lower risk for nonadherence so that intensified efforts at increased monitoring and intervention can be focused on higher-risk patients. CHEST 2010;137(4):883-889 C1 [Localio, A. Russell; Brensinger, Colleen M.; Christie, Jason D.; Gross, Robert; Price, Maureen; Metlay, Joshua P.; Cohen, Abigail; Newcomb, Craig W.; Strom, Brian L.; Kimmel, Stephen E.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Christie, Jason D.; Gross, Robert; Metlay, Joshua P.; Strom, Brian L.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Platt, Alec B.; Gross, Robert; Metlay, Joshua P.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Platt, Alec B.] Reading Hosp Med Ctr, Reading, PA USA. [Localio, A. Russell; Gross, Robert; Metlay, Joshua P.; Strom, Brian L.] Univ Penn, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. [Cruess, Dean G.] Univ Connecticut, Dept Psychol, Storrs, CT USA. [Parker, Catherine S.] Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA 02215 USA. [Laskin, Mitchell S.] Hosp Univ Penn, Dept Pharm Serv, Philadelphia, PA 19104 USA. RP Kimmel, SE (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, 707 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM stevek@mail.med.upenn.edu RI Cohen, Abigail/K-9180-2013 OI Cohen, Abigail/0000-0002-7425-7218 FU National Institutes of Health [R01-HL66176]; Agency for Health Research and Quality [P01-HS11530]; Pfizer; Merck; Novartis; GlaxoSmithKline; Centocor; Bayer; National Institutes of Health; Agency for Health Research and Quality; Aetna Foundation; Bristol-Myers Squibb; [P20RR020741]; [K24HL070936] FX The IN-RANGE study was supported by grants from the National Institutes of Health [R01-HL66176] and the Agency for Health Research and Quality [P01-HS11530]. Dr Kimmel was also supported by P20RR020741 and K24HL070936.; The authors have reported to CHEST the following conflicts of interest: Dr Kimmel has served as a consultant and/or received research funding from several pharmaceutical companies, including Pfizer, Merck, Novartis, GlaxoSmithKline, Centocor, and Bayer, all unrelated to this lover. Dr Kimmel has received investigator-initiated research funding from the National Institutes of Health, the Agency for Health Research and Quality, and the Aetna Foundation for warfarin research. Dr Gross has served as a consultant and/or received research funding from GlaxoSmithKline and Bristol-Myers Squibb, and Dr Strom has served as a consultant to Bristol-Myers Squibb and other pharmaceutical companies, all unrelated to this paper. Drs Platt, Localio, Cruess, Christie, Parker, Meday, and Cohen; Mss Brensinger and Price; and Messrs Newcomb and Laskin have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.; The National Institutes of Health and the Agency for Health Research and Quality, which provided grants, had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, and approval of the manuscript. NR 34 TC 20 Z9 21 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 EI 1931-3543 J9 CHEST JI Chest PD APR PY 2010 VL 137 IS 4 BP 883 EP 889 DI 10.1378/chest.09-0039 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 582XA UT WOS:000276632400021 PM 19903973 ER PT J AU Kurtz, BP Abrams, AN AF Kurtz, Brian P. Abrams, Annah N. TI Psychiatric Aspects of Pediatric Cancer SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Cancer; Psychosocial issues; Psychiatry; Pediatric; Coping ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NEWLY-DIAGNOSED CANCER; LONG-TERM SURVIVORS; CHRONIC HEPATITIS-C; BONE-MARROW-TRANSPLANTATION; INTERFERON-ALPHA TREATMENT; STEM-CELL TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; CHILDRENS ONCOLOGY GROUP; MALIGNANT BRAIN-TUMORS AB The diagnosis and treatment of children and adolescents with cancer has a tremendous and lasting effect on the patients, their families, and other individuals in their social network. It carries a host of psychological and behavioral ramifications, from questions of mortality to changes in levels of functioning in multiple domains. In this review the authors address the psychosocial and treatment-related issues that arise in children with cancer, with attention to the adjustment to cancer at different developmental stages, mood and anxiety issues, treatment-related psychiatric sequelae, and the challenges faced by childhood cancer survivors. C1 [Kurtz, Brian P.; Abrams, Annah N.] Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Boston, MA 02114 USA. [Kurtz, Brian P.] Massachusetts Gen Hosp, McLean Hosp, Child & Adolescent Psychiat Residency Training Pr, Boston, MA 02114 USA. [Abrams, Annah N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Abrams, Annah N.] Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. RP Abrams, AN (reprint author), Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, 55 Fruit St,Yawkey 6A, Boston, MA 02114 USA. EM aabrams@partners.org NR 155 TC 8 Z9 10 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 2010 VL 19 IS 2 BP 401 EP + DI 10.1016/j.chc.2010.01.009 PG 23 WC Psychiatry SC Psychiatry GA 612AI UT WOS:000278867600015 PM 20478507 ER PT J AU Storch, EA McKay, D Reid, JM Geller, DA Goodman, WK Lewin, AB Murphy, TK AF Storch, Eric A. McKay, Dean Reid, Jeannette M. Geller, Daniel A. Goodman, Wayne K. Lewin, Adam B. Murphy, Tanya K. TI D-Cycloserine Augmentation of Cognitive-Behavioral Therapy: Directions for Pilot Research in Pediatric Obsessive-Compulsive Disorder SO CHILD & YOUTH CARE FORUM LA English DT Article DE OCD; Children; Augmentation; D-Cycloserine; Cognitive-behavioral therapy ID METHYL-D-ASPARTATE; FEAR-POTENTIATED STARTLE; SOCIAL ANXIETY DISORDER; EXPOSURE THERAPY; ALZHEIMERS-DISEASE; CONDITIONED FEAR; CONTROLLED-TRIAL; FOLLOW-UP; CLINICAL-IMPLICATIONS; NEGATIVE SYMPTOMS AB This paper discusses a recent translational success in combining behavioral psychotherapy with a novel medication, d-cycloserine (DCS), to augment cognitive-behavioral therapy (CBT) for anxiety disorders. The literature on behavioral theory of exposure-based therapies is provided, followed by a discussion of the role of DCS in enhancing extinction learning that is core to such therapies. As well, pragmatic issues such as dosing and timing are discussed. The manuscript is concluded with consideration of future directions in DCS augmentation in the form of a pilot trial investigating DCS augmentation of CBT in pediatric patients with obsessive-compulsive disorder. C1 [Storch, Eric A.; Reid, Jeannette M.; Lewin, Adam B.; Murphy, Tanya K.] Univ S Florida, Dept Pediat, Rothman Ctr Neuropsychiat, Coll Med, St Petersburg, FL 33701 USA. [Storch, Eric A.; Murphy, Tanya K.] Univ S Florida, Dept Psychiat, St Petersburg, FL 33701 USA. [McKay, Dean] Fordham Univ, Dept Psychol, New York, NY 10023 USA. [Geller, Daniel A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goodman, Wayne K.] Mt Sinai Hosp, New York, NY 10029 USA. RP Storch, EA (reprint author), Univ S Florida, Dept Pediat, Rothman Ctr Neuropsychiat, Coll Med, 800 6th St S 4th Floor, St Petersburg, FL 33701 USA. EM estorch@health.usf.edu RI Storch, Eric/I-4935-2012; Lewin, Adam/A-9832-2013; Murphy, Tanya/J-7079-2013 NR 83 TC 5 Z9 5 U1 4 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1053-1890 EI 1573-3319 J9 CHILD YOUTH CARE FOR JI Child Youth Care Forum PD APR PY 2010 VL 39 IS 2 SI SI BP 101 EP 112 DI 10.1007/s10566-010-9094-6 PG 12 WC Psychology, Developmental SC Psychology GA 665AJ UT WOS:000283005800004 ER PT J AU Lewis, GD Gerszten, RE AF Lewis, Gregory D. Gerszten, Robert E. TI Toward Metabolomic Signatures of Cardiovascular Disease SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Editorial Material DE cardiovascular diseases; genetics; metabolomics; functional genomics; atherosclerosis ID INSULIN-RESISTANCE; IDENTIFICATION; HUMANS; OBESE; ACIDS C1 [Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, E 8307,149 13th St, Charlestown, MA 02129 USA. EM rgerszten@partners.org FU NHLBI NIH HHS [K23 HL091106-03, K23HL091106, R01 HL072872, K23 HL091106]; NIDDK NIH HHS [R01 DK081572, R01 DK081572-02, R01 DK081572-04, R01 DK081572-01, R01DK081572, R01 DK081572-01S1, R01 DK081572-03] NR 15 TC 13 Z9 13 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD APR PY 2010 VL 3 IS 2 BP 119 EP 121 DI 10.1161/CIRCGENETICS.110.954941 PG 3 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 586BR UT WOS:000276876400001 PM 20407099 ER PT J AU Ko, DT Yun, LS Wijeysundera, HC Jackevicius, CA Rao, SV Austin, PC Marquis, JF Tu, JV AF Ko, Dennis T. Yun, Lingsong Wijeysundera, Harindra C. Jackevicius, Cynthia A. Rao, Sunil V. Austin, Peter C. Marquis, Jean-Francois Tu, Jack V. TI Incidence, Predictors, and Prognostic Implications of Hospitalization for Late Bleeding After Percutaneous Coronary Intervention for Patients Older Than 65 Years SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE bleeding; percutaneous coronary intervention; mortality; oral anticoagulants ID EXPERT CONSENSUS DOCUMENT; ST-SEGMENT-ELEVATION; DRUG-ELUTING STENTS; ANTIPLATELET THERAPY; ATRIAL-FIBRILLATION; MYOCARDIAL-INFARCTION; BLOOD-TRANSFUSION; ADVERSE OUTCOMES; RISK; TRIAL AB Background-Previous data on bleeding after percutaneous coronary intervention (PCI) have been obtained primarily from randomized trials that focused on in-hospital bleeding. The incidence of late bleeding after PCI, its independent predictors, and its prognostic importance in clinical practice has not been fully addressed. Methods and Results-We evaluated 22 798 patients aged >65 years who underwent PCI from December 1, 2003, to March 31, 2007, in Ontario, Canada. Cox proportional hazard models were used to determine factors associated with late bleeding, which was defined as hospitalization for bleeding after discharge from the index PCI, and to estimate risk of death or myocardial infarction associated with late bleeding. We found that 2.5% of patients were hospitalized for bleeding in the year after PCI, with 56% of bleeding episodes due to gastrointestinal bleed. The most significant predictor of late bleeding was warfarin use after PCI (hazard ratio [HR], 3.12). Other significant predictors included age (HR, 1.41 per 10 years), male sex (HR, 1.24), cancer (HR, 1.80), previous bleeding (HR, 2.42), chronic kidney disease (HR, 1.93), and nonsteroidal antiinflammatory drug use (HR, 1.73). After adjusting for baseline covariates, hospitalization for a bleeding episode was associated with a significantly increased 1-year hazard of death or myocardial infarction (HR, 2.39; 95% CI, 1.93 to 2.97) and death (HR, 3.38; 95% CI, 2.60 to 4.40). Conclusions-Hospitalization for late bleeding after PCI is associated with substantially increased risk of death and myocardial infarction. The use of triple therapy (ie, aspirin, thienopyridine, and warfarin) is associated with the highest risk of late bleeding. (Circ Cardiovasc Interv. 2010;3:140-147.) C1 [Ko, Dennis T.; Wijeysundera, Harindra C.; Tu, Jack V.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Schulich Heart Ctr, Div Cardiol, Toronto, ON, Canada. [Ko, Dennis T.; Jackevicius, Cynthia A.; Austin, Peter C.; Tu, Jack V.] Univ Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Pomona, CA USA. [Jackevicius, Cynthia A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Rao, Sunil V.] Duke Clin Res Inst, Durham, NC USA. [Marquis, Jean-Francois] Univ Ottawa, Inst Heart, Ottawa, ON, Canada. RP Ko, DT (reprint author), Inst Clin Evaluat Sci G1 06, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM dennis.ko@ices.on.ca OI Ko, Dennis/0000-0001-6840-8051; Tu, Jack/0000-0003-0111-722X; Austin, Peter/0000-0003-3337-233X FU Ontario Health Technology Advisory Committee; Medical Advisory Secretariat; Canadian Institutes of Health Research (CIHR) [82747]; Heart and Stroke Foundation of Ontario (HSFO); HSFO; Institute for Clinical Evaluative Sciences; Cardiac Care Network of Ontario; Ministry of Health and Long-Term Care FX We acknowledge that the data used in this publication are from the Cardiac Care Network of Ontario and its member hospitals. The Cardiac Care Network of Ontario serves as an advisory body to the Ministry of Health and Long-Term Care and is dedicated to improving the quality, efficiency, access, and equity of adult cardiovascular services in Ontario, Canada. We also acknowledge the support from the Ontario Health Technology Advisory Committee and the Medical Advisory Secretariat.; This study was funded by an operating grant from the Canadian Institutes of Health Research (CIHR) (MOP 82747). Dr Ko was supported by a Clinician-Scientist Award from the Heart and Stroke Foundation of Ontario (HSFO) and a New Investigator award by CIHR. Dr Austin was supported by a Career Investigator Award by the HSFO. Dr Tu was supported by a Canada Research Chair in Health Services Research and a Career Investigator Award from the HSFO. Dr Wijeysundera was supported by a research fellowship award from the CIHR. The Institute for Clinical Evaluative Sciences, Cardiac Care Network of Ontario, and Programs for Assessment of Technology in Health Research Institute were funded by the Ministry of Health and Long-Term Care. NR 37 TC 33 Z9 34 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD APR PY 2010 VL 3 IS 2 BP 140 EP U73 DI 10.1161/CIRCINTERVENTIONS.109.928721 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 586AP UT WOS:000276873400009 PM 20332382 ER PT J AU Waxman, S Freilich, MI Suter, MJ Shishkov, M Bilazarian, S Virmani, R Bouma, BE Tearney, GJ AF Waxman, Sergio Freilich, Mark I. Suter, Melissa J. Shishkov, Milen Bilazarian, Seth Virmani, Renu Bouma, Brett E. Tearney, Gary J. TI A Case of Lipid Core Plaque Progression and Rupture at the Edge of a Coronary Stent: Elucidating the Mechanisms of Drug-Eluting Stent Failure SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material C1 [Freilich, Mark I.; Shishkov, Milen; Bouma, Brett E.; Tearney, Gary J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Suter, Melissa J.; Shishkov, Milen; Bouma, Brett E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tearney, Gary J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Waxman, Sergio] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Waxman, Sergio; Freilich, Mark I.; Bilazarian, Seth] Lahey Clin Fdn, Dept Cardiovasc Med, Burlington, MA USA. [Tearney, Gary J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Suter, Melissa J.; Shishkov, Milen; Bouma, Brett E.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Bouma, Brett E.; Tearney, Gary J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Virmani, Renu] CVPath Inst Inc, Gaithersburg, MD USA. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 55 Fruit St,BAR 703, Boston, MA 02114 USA. EM gtearney@partners.org FU NHLBI NIH HHS [5R01HL076398, R01 HL076398, R01 HL076398-05, R01 HL093717, R01 HL093717-03] NR 4 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD APR PY 2010 VL 3 IS 2 BP 193 EP 196 DI 10.1161/CIRCINTERVENTIONS.109.917955 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 586AP UT WOS:000276873400015 PM 20407116 ER PT J AU Irazoqui, JE Ausubel, FM AF Irazoqui, J. E. Ausubel, F. M. TI 99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Caenorhabditis elegans as a model to study tissues involved in host immunity and microbial pathogenesis SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE anti-microbial; C; elegans; defence; infection; innate immunity ID TOLL-LIKE RECEPTOR; INNATE IMMUNITY; C. ELEGANS; PSEUDOMONAS-AERUGINOSA; LIFE-SPAN; MICROBACTERIUM-NEMATOPHILUM; SIGNALING PATHWAY; BACTERIAL PATHOGEN; RECTAL INFECTION; GENETIC-ANALYSIS AB P>The molecular mechanisms involved in host-microbe interactions during the initial stages of infection are poorly understood. The bacteria-eating nematode Caenorhabditis elegans provides an opportunity to dissect host-microbe interactions in the context of the whole organism, using powerful genomic, genetic and cell-biological tools. Because of the evolutionary conservation of ancient innate host defences and bacterial virulence mechanisms, studies in C. elegans hold great promise to shed light on defences in higher organisms, including mammals. Additionally, C. elegans pathogenesis models provide a platform for the identification of novel classes of anti-infective compounds with therapeutic value. C1 [Irazoqui, J. E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Irazoqui, JE (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu RI Irazoqui, Javier/A-8028-2013; OI Irazoqui, Javier/0000-0001-6553-1329 FU NIAID NIH HHS [P01 AI044220]; NIDDK NIH HHS [P30 DK040561, P30 DK043351, P30 DK040561-15] NR 62 TC 14 Z9 15 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2010 VL 160 IS 1 BP 48 EP 57 DI 10.1111/j.1365-2249.2010.04122.x PG 10 WC Immunology SC Immunology GA 567JN UT WOS:000275443000008 PM 20415851 ER PT J AU Silvers, AL Lin, L Bass, AJ Chen, GA Wang, ZW Thomas, DG Lin, J Giordano, TJ Orringer, MB Beer, DG Chang, AC AF Silvers, Amy L. Lin, Lin Bass, Adam J. Chen, Guoan Wang, Zhuwen Thomas, Dafydd G. Lin, Jules Giordano, Thomas J. Orringer, Mark B. Beer, David G. Chang, Andrew C. TI Decreased Selenium-Binding Protein 1 in Esophageal Adenocarcinoma Results from Posttranscriptional and Epigenetic Regulation and Affects Chemosensitivity SO CLINICAL CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER CELLS; EPIDERMAL DIFFERENTIATION COMPLEX; GENE-EXPRESSION PROFILES; MAMMARY EPITHELIAL-CELLS; METHYLSELENINIC ACID; DNA METHYLATION; SURVIVAL; PROGRESSION; LUNG; SUPPRESSION AB Purpose: The chemopreventive effects of selenium have been extensively examined, but its role in cancer development or as a chemotherapeutic agent has only recently been explored. Because selenium-binding protein 1 (SELENBP1, SBP1, hSP56) has been shown to bind selenium covalently and selenium deficiency has been associated with esophageal adenocarcinoma (EAC), we examined its role in EAC development and its potential effect on chemosensitivity in the presence of selenium. Experimental Design: SELENBP1 expression level and copy number variation were determined by oligonucleotide microarrays, real-time reverse transcription-PCR, tissue microarrays, immunoblotting, and single-nucleotide polymorphism arrays. Bisulfite sequencing and sequence analysis of reverse transcription-PCR-amplified products explored epigenetic and posttranscriptional regulation of SELENBP1 expression, respectively. WST-1 cell proliferation assays, senescence-associated beta-galactosidase staining, immunoblotting, and flow cytometry were done to evaluate the biological significance of SELENBP1 overexpression in selenium-supplemented EAC cells. Results: SELENBP1 expression decreased significantly in Barrett's esophagus to adenocarcinoma progression. Both epigenetic and posttranscriptional mechanisms seemed to modulate SELENBP1 expression. Stable overexpression of SELENBP1 in methylseleninic acid-supplemented Flo-1 cells resulted in enhanced apoptosis, increased cellular senescence, and enhanced cisplatin cytotoxicity. Although inorganic sodium selenite similarly enhanced cisplatin cytotoxicity, these two forms of selenium elicited different cellular responses. Conclusions: SELENBP1 expression may be an important predictor of response to chemoprevention or chemosensitization with certain forms of selenium in esophageal tissues. Clin Cancer Res; 16(7); 2009-21. (C)2010 AACR. C1 [Silvers, Amy L.; Lin, Lin; Chen, Guoan; Wang, Zhuwen; Lin, Jules; Orringer, Mark B.; Beer, David G.; Chang, Andrew C.] Univ Michigan, Sch Med, Dept Surg, Thorac Surg Sect, Ann Arbor, MI 48109 USA. [Thomas, Dafydd G.; Giordano, Thomas J.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Bass, Adam J.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Cambridge, MA 02138 USA. [Bass, Adam J.] MIT, Broad Inst, Cambridge, MA 02139 USA. RP Chang, AC (reprint author), Univ Michigan, Sch Med, Dept Surg, Thorac Surg Sect, TC2120G-5344,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM andrwchg@umich.edu OI Chang, Andrew/0000-0001-9506-0425; Giordano, Thomas/0000-0003-0641-8873 FU NIH [5R01CA071606, 5P30CA046592, 5K08CA134931, 5K08CA127212]; Thoracic Surgery Foundation for Research and Education FX NIH grants 5R01CA071606 (D. G. Beer), 5P30CA046592 (T.J. Giordano), 5K08CA134931(A.J. Bass), and 5K08CA127212 (A. C. Chang) and Thoracic Surgery Foundation for Research and Education (A. C. Chang). NR 47 TC 33 Z9 36 U1 0 U2 4 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 1 PY 2010 VL 16 IS 7 BP 2009 EP 2021 DI 10.1158/1078-0432.CCR-09-2801 PG 13 WC Oncology SC Oncology GA 608OV UT WOS:000278595800005 PM 20332323 ER PT J AU Juszczynski, P Rodig, SJ Ouyang, J O'Donnell, E Takeyama, K Mlynarski, W Mycko, K Szczepanski, T Gaworczyk, A Krivtsov, A Faber, J Sinha, AU Rabinovich, GA Armstrong, SA Kutok, JL Shipp, MA AF Juszczynski, Przemyslaw Rodig, Scott J. Ouyang, Jing O'Donnell, Evan Takeyama, Kunihiko Mlynarski, Wojciech Mycko, Katarzyna Szczepanski, Tomasz Gaworczyk, Anna Krivtsov, Andrei Faber, Joerg Sinha, Amit U. Rabinovich, Gabriel A. Armstrong, Scott A. Kutok, Jeffery L. Shipp, Margaret A. TI MLL-Rearranged B Lymphoblastic Leukemias Selectively Express the Immunoregulatory Carbohydrate-Binding Protein Galectin-1 SO CLINICAL CANCER RESEARCH LA English DT Article ID MINIMAL RESIDUAL DISEASE; TUMOR-IMMUNE PRIVILEGE; GENE-EXPRESSION; BONE-MARROW; CLASSICAL HODGKIN; ONCOLOGY-GROUP; T-CELLS; INFANTS; TRANSLOCATIONS; ABNORMALITIES AB Purpose: Patients with mixed lineage leukemia (MLL)-rearranged B-lymphoblastic leukemias (B-ALL) have an unfavorable prognosis and require intensified treatment. Multiple MLL fusion partners have been identified, complicating the diagnostic evaluation of MLL rearrangements. We analyzed molecular markers of MLL rearrangement for use in rapid diagnostic assays and found the immunomodulatory protein, Galectin-1 (Gal-1), to be selectively expressed in MLL-rearranged B-ALL. Experimental Design: Transcriptional profiling of ALL subtypes revealed selective overexpression of Gal-1 in MLL-rearranged ALLs. For this reason, we analyzed Gal-1 protein expression in MLL-germline and MLL-rearranged adult and infant pediatric B-ALLs and cell lines by immunoblotting, immunohistochemistry, and intracellular flow cytometry of viable tumor cell suspensions. Because deregulated gene expression in MLL-rearranged leukemias may be related to the altered histone methyltransferase activity of the MLL fusion protein complex, we also analyzed histone H3 lysine 79 (H3K79) dimethylation in the LGALS1 promoter region using chromatin immunoprecipitation. Results: Gal-1 transcripts were significantly more abundant in MLL-rearranged B-ALLs. All 32 primary MLL-rearranged B-ALLs exhibited abundant Gal-1 immunostaining, regardless of the translocation partner, whereas only 2 of 81 germline-MLL B-ALLs expressed Gal-1. In addition, Gal-1 was selectively detected in newly diagnosed MLL-rearranged B-ALLs by intracellular flow cytometry. The LGALS1 promoter H3K79 was significantly hypermethylated in MLL-rearranged B-ALLs compared with MLL-germline B-ALLs and normal pre-B cells. Conclusion: In B-ALL, Gal-1 is a highly sensitive and specific biomarker of MLL rearrangement that is likely induced by a MLL-dependent epigenetic modification. Clin Cancer Res; 16(7); 2122-30. (C)2010 AACR. C1 [Rodig, Scott J.; Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Juszczynski, Przemyslaw; Ouyang, Jing; O'Donnell, Evan; Takeyama, Kunihiko; Shipp, Margaret A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Krivtsov, Andrei; Faber, Joerg; Sinha, Amit U.; Armstrong, Scott A.] Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. [Mlynarski, Wojciech; Mycko, Katarzyna] Med Univ Lodz, Dept Pediat Hematol Oncol & Diabetol, Lodz, Poland. [Szczepanski, Tomasz] Med Univ Silesia, Dept Pediat Hematol & Oncol, Zabrze, Poland. [Gaworczyk, Anna] Med Univ Lublin, Dept Pediat Hematol & Oncol, Lublin, Poland. [Rabinovich, Gabriel A.] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, Immunopathol Lab, RA-1033 Buenos Aires, DF, Argentina. RP Kutok, JL (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jkutok@partners.org; margaret_shipp@dfci.harvard.edu RI Faber, Joerg/G-4549-2010 FU NCI NIH HHS [P01 CA092625, P01 CA092625-09] NR 43 TC 14 Z9 14 U1 0 U2 4 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 1 PY 2010 VL 16 IS 7 BP 2122 EP 2130 DI 10.1158/1078-0432.CCR-09-2765 PG 9 WC Oncology SC Oncology GA 608OV UT WOS:000278595800016 PM 20332322 ER PT J AU Nichols, AC Finkelstein, DM Faquin, WC Westra, WH Mroz, EA Kneuertz, P Begum, S Michaud, WA Busse, PM Clark, JR Rocco, JW AF Nichols, Anthony C. Finkelstein, Dianne M. Faquin, William C. Westra, William H. Mroz, Edmund A. Kneuertz, Peter Begum, Shahnaz Michaud, William A. Busse, Paul M. Clark, John R. Rocco, James W. TI Bcl2 and Human Papilloma Virus 16 as Predictors of Outcome following Concurrent Chemoradiation for Advanced Oropharyngeal Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; NECK-CANCER; ORGAN PRESERVATION; TUMOR-ORIGIN; HEAD; EXPRESSION; SURVIVAL; P16; CHEMOTHERAPY; CISPLATIN AB Purpose: Oropharyngeal squamous cell carcinoma (OPSCC) associated with human papilloma virus (HPV) is rapidly growing in incidence. Despite better prognosis than OPSCC associated with traditional risk factors, treatment failure still occurs in a significant proportion of patients. We had identified the antiapoptotic protein Bcl2 as a marker for poor outcome in advanced OPSCC treated with concurrent chemoradiation. To determine whether Bcl2 and HPV together might further characterize treatment response, we examined whether the prognostic value of Bcl2 was independent of HPV status. Experimental Design: Pretreatment tumor biopsies from 68 OPSCC patients were tested for HPV by in situ hybridization and were immunostained for Bcl2 to evaluate relations with disease-free (DFS) and overall survival following platin-based concurrent chemoradiation. Median follow-up among surviving patients was 47 months (range, 10-131 months). Results: Bcl2 and HPV independently predicted DFS and overall survival. Hazard ratios (with 95% confidence interval) for positive versus negative status in bivariate Cox proportional hazard analysis of DFS were 6.1 (1.8-21) for Bcl2 and 0.11 (0.035-0.37) for HPV. Only 1 of 32 HPV-positive/Bcl2-negative tumors recurred. Pretreatment Bcl2 expression was specifically associated with distant metastasis; five of six distant metastases occurred in the <40% of patients whose primary tumors were Bcl2 positive. Conclusions: Independent of HPV status, pretreatment Bcl2 expression identifies a subset of OPSCC patients having increased risk of treatment failure, particularly through distant metastasis, after concurrent chemoradiation. Considering HPV and Bcl2 together should help in devising better personalized treatments for OPSCC. Clin Cancer Res; 16(7); 2138-46. (C)2010 AACR. C1 [Rocco, James W.] Massachusetts Gen Hosp, Ctr Canc, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Finkelstein, Dianne M.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mroz, Edmund A.; Michaud, William A.; Rocco, James W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Busse, Paul M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Clark, John R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Westra, William H.; Begum, Shahnaz] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. RP Rocco, JW (reprint author), Massachusetts Gen Hosp, Ctr Canc, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 55 Fruit St, Boston, MA 02114 USA. EM jrocco@partners.org FU Laurence Murphy Fund; Norman Knight Fund; James Kelly Fund for Head and Neck Research; Flight Attendant Medical Research Institute FX The Laurence Murphy Fund, the Norman Knight Fund, the James Kelly Fund for Head and Neck Research, and the Flight Attendant Medical Research Institute (J.W. Rocco). NR 34 TC 36 Z9 41 U1 0 U2 1 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 1 PY 2010 VL 16 IS 7 BP 2138 EP 2146 DI 10.1158/1078-0432.CCR-09-3185 PG 9 WC Oncology SC Oncology GA 608OV UT WOS:000278595800018 PM 20233885 ER PT J AU Brown, J Nallamshetty, S Plutzky, J AF Brown, Jonthan Nallamshetty, Shriram Plutzky, Jorge TI Intersecting Vectors of Basic Science Research and Clinical Medicine: LOX-1? SO CLINICAL CHEMISTRY LA English DT Editorial Material ID DENSITY-LIPOPROTEIN RECEPTOR; CARDIOVASCULAR RISK; STROKE; PREDICTION; BIOMARKERS; INSIGHTS; PROTEIN; DISEASE C1 [Brown, Jonthan; Nallamshetty, Shriram] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Nallamshetty, Shriram; Plutzky, Jorge] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Plutzky, J (reprint author), 77 Ave Louis Pasteur,NRB 742, Boston, MA 02115 USA. EM jplutzly@rics.bwh.harvard.edu NR 15 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR 1 PY 2010 VL 56 IS 4 BP 499 EP 501 DI 10.1373/clinchem.2009.142232 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 588HN UT WOS:000277059900001 PM 20185618 ER PT J AU Truong, QA Siegel, E Karakas, M Januzzi, JL Bamberg, F Mahabadi, AA Dasdemir, S Brady, TJ Bergmann, A Kunde, J Nagurney, JT Hoffmann, U Koenig, W AF Truong, Quynh A. Siegel, Emily Karakas, Mahir Januzzi, James L., Jr. Bamberg, Fabian Mahabadi, Amir A. Dasdemir, Selcuk Brady, Thomas J. Bergmann, Andreas Kunde, Jan Nagurney, John T. Hoffmann, Udo Koenig, Wolfgang TI Relation of Natriuretic Peptides and Midregional Proadrenomedullin to Cardiac Chamber Volumes by Computed Tomography in Patients without Heart Failure: From the ROMICAT Trial SO CLINICAL CHEMISTRY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PROGNOSTIC VALUE; PRO-ADRENOMEDULLIN; IMMUNOLUMINOMETRIC ASSAY; CARDIOVASCULAR EVENTS; PLASMA; PROATRIAL; PREDICTION; BIOMARKERS; ATRIAL AB BACKGROUND: Stress myocyte biomarkers are used prognostically in patients with cardiovascular disease. We examined associations between amino-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-A-type natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM) concentrations and cardiac chamber volumes in chest pain patients without heart failure by use of computed tomography (CT). METHODS: At the time of 64-slice CT scan, we acquired plasma and serum samples for these biomarkers from 346 patients [mean (SD) age 53 (12) years, 65% men]. Left atrial volume (LAV) and left ventricular volumes at end-diastole (LVEDV) and end-systole (LVESV) were measured and indexed to body surface area (LAVI, LVEDI, LVESI). RESULTS: Concentrations of both natriuretic peptides were correlated with LAV and LAVI (r = 0.19-0.32, all P <= 0.0005) and MR-proADM with LV volumes and indices (r = -0.14 to -0.21, all P <= 0.01). NT-proBNP and MR-proANP concentrations were higher in the top quartiles of patients than the lowest quartiles using LAV and LAVI, whereas MR-proADM concentrations were lower in the top quartiles of LV measures. In adjusted analyses, patients had 2- to 4-fold increased risk of LA enlargement for every incremental increase in log(10)NT-proBNP [LAV odds ratio (OR) 2.4, P = 0.03; LAVI OR 4.0, P = 0.003] and 10- to 13-fold increased risk of LA enlargement for every incremental increase in log(10)MR-proANP (LAV OR 10.7, P = 0.009; LAVI OR 13.1, P = 0.004). CONCLUSIONS: In patients without heart failure, both NT-proBNP and MR-proANP concentrations are independently associated with LA enlargement, whereas MR-proADM concentrations are correlated with LV volumes. This may partially explain the well-recognized value of natriuretic peptides for use in risk stratification. (C) 2010 American Association for Clinical Chemistry C1 [Truong, Quynh A.; Siegel, Emily; Bamberg, Fabian; Mahabadi, Amir A.; Brady, Thomas J.; Hoffmann, Udo] Harvard Univ, Cardiac MR PET CT Program, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Boston, MA 02114 USA. [Truong, Quynh A.; Januzzi, James L., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Nagurney, John T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Karakas, Mahir; Dasdemir, Selcuk; Koenig, Wolfgang] Univ Ulm, Div Cardiol, Ulm, Germany. [Bergmann, Andreas; Kunde, Jan] BRAHMS CO, Hennigsdorf, Germany. RP Truong, QA (reprint author), Harvard Univ, Cardiac MR PET CT Program, Sch Med, Massachusetts Gen Hosp,Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM qtruong@partners.org FU Roche Diagnostics; NIH [T32HL076136, L30HL093896, R01 HL080053]; German National Academic Foundation; Siemens Medical Solutions; General Electrics Healthcare FX J.L. Januzzi, Roche Diagnostics; Q.A. Truong, NIH grant T32HL076136 and L30HL093896; J. L. Januzzi, Balson Cardiac Scholar Award; A. A. Mahabadi, grant from the German National Academic Foundation. This work was supported by the NIH R01 HL080053, and in part supported by Siemens Medical Solutions and General Electrics Healthcare. Reagents for measurement of the natriuretic peptides were kindly provided for free by the BRAHMS CO. NR 39 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR 1 PY 2010 VL 56 IS 4 BP 651 EP 660 DI 10.1373/clinchem.2009.138586 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 588HN UT WOS:000277059900025 PM 20185624 ER PT J AU Abraham, NS Hartman, C Hasche, J AF Abraham, Neena S. Hartman, Christine Hasche, Jennifer TI Reduced Hospitalization Cost for Upper Gastrointestinal Events That Occur Among Elderly Veterans Who Are Gastroprotected SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Comparative Effectiveness; Administrative Database; Department of Veterans Affairs; Gastrointestinal Hemorrhage; Health Resource Use ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RHEUMATOID-ARTHRITIS; RESOURCE UTILIZATION; ULCER COMPLICATIONS; NONSELECTIVE NSAIDS; MANAGED CARE; DOUBLE-BLIND; RISK; PREVENTION; ASPIRIN AB BACKGROUND & AIMS: Despite prescription of gastro-protection among elderly nonsteroidal anti-inflammatory drug (NSAID) users, residual bleeding can still occur. We sought to determine the effect of proton pump inhibitors (PPI) on hospitalization and resource use among veterans in whom an upper gastrointestinal event (UGIE) occurred. METHODS: We identified from national pharmacy records veterans >= 65 years prescribed an NSAID, cyclooxygenase-2 selective NSAID (coxib), or salicylate (>325 mg/day) at any Veterans Affairs (VA) facility (01/01/00-12/31/04). Prescription fill data were linked longitudinally to a Veterans Affairs-Medicare dataset of inpatient, outpatient, and death files, and demographic and provider data. Among veterans in whom a UGIE occurred, we assessed the effect of prescription strategy on hospitalization, using a multivariate logistic regression model. RESULTS: A total of 3566 UGIEs occurred among a cohort that was predominantly male (97.5%), white (77%), with a mean age of 73.5 (SD, 5.7). Hospitalization occurred in 47.5%, and gastroprotection was associated with a 30% reduction in hospitalization compared with no PPI. Five-year pharmacy costs associated with the PPI strategy exceeded the no-PPI strategy ($742,406 vs $184,282); however, a substantial reduction in medical costs was observed with PPI ($9,948,738 vs $18,686,081). CONCLUSIONS: Even if an NSAID-UGIE occurs in the PPI-protected older veteran, the reduction in need for hospitalization results in a cost saving to the Department of Veterans Affairs. C1 [Abraham, Neena S.; Hartman, Christine; Hasche, Jennifer] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. [Abraham, Neena S.] Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [Hartman, Christine] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Abraham, NS (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM nabraham@bcm.edu FU American Gastroenterological Association Foundation; Department of Veterans Affairs (VA) [IIR 115-05]; American Digestive Health Foundation Outcomes Research Award; Astra Zeneca Pharmaceuticals; Houston Center for Quality of Care & Utilization Studies, Houston Veterans Affairs Medical Center [HFP90-020] FX This study was funded in part by an American Gastroenterological Association Foundation-Sucampo-ASP Designated Research Award in Geriatric Gastroenterology, a Merit Review Award from the Department of Veterans Affairs (VA) (IIR 115-05), an American Digestive Health Foundation Outcomes Research Award, and an investigator-initiated research grant from Astra Zeneca Pharmaceuticals. This material is the result of work supported with resources and the use of facilities at the Houston Center for Quality of Care & Utilization Studies, Houston Veterans Affairs Medical Center (HFP90-020). NR 38 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2010 VL 8 IS 4 BP 350 EP 356 DI 10.1016/j.cgh.2010.01.002 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 584WP UT WOS:000276784700011 PM 20096378 ER PT J AU Reddy, KP Brady, MF Gilman, RH Coronel, J Navincopa, M Ticona, E Chavez, G Sanchez, E Rojas, C Solari, L Valencia, J Pinedo, Y Benites, C Friedland, JS Moore, DAJ AF Reddy, Krishna P. Brady, Mark F. Gilman, Robert H. Coronel, Jorge Navincopa, Marcos Ticona, Eduardo Chavez, Gonzalo Sanchez, Eduardo Rojas, Christian Solari, Lely Valencia, Jorge Pinedo, Yvett Benites, Carlos Friedland, Jon S. Moore, David A. J. TI Microscopic Observation Drug Susceptibility Assay for Tuberculosis Screening before Isoniazid Preventive Therapy in HIV-Infected Persons SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HUMAN-IMMUNODEFICIENCY-VIRUS; MYCOBACTERIUM-TUBERCULOSIS; ACTIVE TUBERCULOSIS; PULMONARY TUBERCULOSIS; RESISTANT TUBERCULOSIS; DEVELOPING-COUNTRIES; CHEST RADIOGRAPHY; DIAGNOSTIC-TEST; SOUTH-AFRICA AB Background. Active tuberculosis (TB) must be excluded before initiating isoniazid preventive therapy (IPT) in persons infected with human immunodeficiency virus (HIV), but currently used screening strategies have poor sensitivity and specificity and high patient attrition rates. Liquid TB culture is now recommended for the detection of Mycobacterium tuberculosis in individuals suspected of having TB. This study compared the efficacy, effectiveness, and speed of the microscopic observation drug susceptibility (MODS) assay with currently used strategies for TB screening before IPT in HIV-infected persons. Methods. A total of 471 HIV-infected IPT candidates at 3 hospitals in Lima, Peru, were enrolled in a prospective comparison of TB screening strategies, including laboratory, clinical, and radiographic assessments. Results. Of 435 patients who provided 2 sputum samples, M. tuberculosis was detected in 27 (6.2%) by MODS culture, 22 (5.1%) by Lowenstein-Jensen culture, and 7 (1.6%) by smear. Of patients with any positive microbiological test result, a MODS culture was positive in 96% by 14 days and 100% by 21 days. The MODS culture simultaneously detected multidrug-resistant TB in 2 patients. Screening strategies involving combinations of clinical assessment, chest radiograph, and sputum smear were less effective than 2 liquid TB cultures in accurately diagnosing and excluding TB (P < .01). Screening strategies that included nonculture tests had poor sensitivity and specificity. Conclusions. MODS culture identified and reliably excluded cases of pulmonary TB more accurately than other screening strategies, while providing results significantly faster than Lowenstein-Jensen culture. Streamlining of the ruling out of TB through the use of liquid culture-based strategies could help facilitate the massive up-scaling of IPT required to reduce HIV and TB morbidity and mortality. C1 [Reddy, Krishna P.; Brady, Mark F.; Gilman, Robert H.; Coronel, Jorge; Moore, David A. J.] Univ Peruana Cayetano Heredia, Lab Invest Enfermedades Infecciosas, Lima, Peru. [Navincopa, Marcos; Ticona, Eduardo; Chavez, Gonzalo] Hosp Nacl Dos de Mayo, Lima, Peru. [Sanchez, Eduardo; Rojas, Christian; Solari, Lely] Hosp Nacl Hipolito Unanue, Lima, Peru. [Valencia, Jorge; Pinedo, Yvett; Benites, Carlos] Hosp Nacl Gen Arzobispo Loayza, Lima, Peru. [Reddy, Krishna P.] Harvard Univ, Sch Med, Boston, MA USA. [Brady, Mark F.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Gilman, Robert H.; Moore, David A. J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Gilman, Robert H.; Friedland, Jon S.; Moore, David A. J.] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis & Immun, London, England. [Gilman, Robert H.; Friedland, Jon S.; Moore, David A. J.] Univ London Imperial Coll Sci Technol & Med, Wellcome Trust Ctr Clin Trop Med, London, England. RP Reddy, KP (reprint author), Massachusetts Gen Hosp, Dept Med, GRB 740,55 Fruit St, Boston, MA 02114 USA. EM kreddy@post.harvard.edu FU Wellcome Trust [078067/Z/05]; National Institutes of Health/Fogarty Global Research [3D43 TW006581-04S1]; National Institutes of Health/Fogarty International Clinical Research; National Institute for Health Research Biomedical Research Centre FX Financial support. This work was supported by Wellcome Trust Career Development Fellowship 078067/Z/05 (D. A. J. M.), National Institutes of Health/Fogarty Global Research Training grant 3D43 TW006581-04S1 (R. H. G.), and National Institutes of Health/Fogarty International Clinical Research Scholar Awards (K. P. R. and M. F. B.). J. S. F. and D. A. J. M. are grateful for support from the National Institute for Health Research Biomedical Research Centre funding scheme. NR 34 TC 14 Z9 14 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2010 VL 50 IS 7 BP 988 EP 996 DI 10.1086/651081 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 563YO UT WOS:000275176900006 PM 20192727 ER PT J AU Devine, H Tierney, DK Schmit-Pokorny, K McDermott, K AF Devine, Hollie Tierney, D. Kathryn Schmit-Pokorny, Kim McDermott, Kathleen TI Mobilization of Hematopoietic Stem Cells for Use in Autologous Transplantation SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID COLONY-STIMULATING FACTOR; NON-HODGKINS-LYMPHOMA; PLUS G-CSF; HIGH-DOSE CYCLOPHOSPHAMIDE; BLOOD PROGENITOR CELLS; BONE-MARROW-TRANSPLANTATION; PERIPHERAL-BLOOD; MULTIPLE-MYELOMA; CXCR4 ANTAGONIST; RANDOMIZED-TRIAL AB Autologous hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach for various malignant hematologic and lymphoid diseases. Hematopoietic stem cells (HSCs) may be collected from the blood or the bone marrow. HSCs are capable of self-renewal and give rise to progenitor cells, multipotent cells that differentiate and proliferate into the mature cells of the blood and immune system. HSCs and progenitor cells are released from the bone marrow into the peripheral blood through a process called mobilization. HSCs then are collected from the blood in a process called apheresis and cryopreserved for administration following the high-dose preparative regimen. This article reviews stem cell biology, current mobilization strategies, use of novel mobilization agents, and nursing care of patients during the mobilization phase of autologous HSCT. Understanding the biology and process of HSC mobilization is critical for transplantation nurses to deliver and coordinate care during this complex phase of autologous HSCT. C1 [Devine, Hollie] Ohio State Univ, Med Ctr, James Canc Hosp, Columbus, OH 43210 USA. [Tierney, D. Kathryn] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Schmit-Pokorny, Kim] Univ Nebraska Med Ctr, Omaha, NE USA. [McDermott, Kathleen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Devine, H (reprint author), Ohio State Univ, Med Ctr, James Canc Hosp, Columbus, OH 43210 USA. EM hollie.devine@osumc.edu NR 65 TC 5 Z9 5 U1 0 U2 3 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD APR PY 2010 VL 14 IS 2 BP 212 EP 222 DI 10.1188/10.CJON.212-222 PG 11 WC Oncology; Nursing SC Oncology; Nursing GA 582HO UT WOS:000276587700017 PM 20350895 ER PT J AU Dimopoulos, MA Chen, C Kastritis, E Gavriatopoulou, M Treon, SP AF Dimopoulos, Meletios A. Chen, Christine Kastritis, Efstathios Gavriatopoulou, Maria Treon, Steven P. TI Bortezomib as a Treatment Option in Patients With Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article DE IgM flares; Immunoglobulin M; Nuclear factor-kappa B; Waldenstrom's macroglobulinemia ID RELAPSED MULTIPLE-MYELOMA; PROTEASOME INHIBITOR BORTEZOMIB; TUMOR LYSIS SYNDROME; CONSENSUS PANEL RECOMMENDATIONS; ENDOPLASMIC-RETICULUM STRESS; 2ND INTERNATIONAL WORKSHOP; COOPERATIVE-ONCOLOGY-GROUP; IGM MONOCLONAL GAMMOPATHY; MANTLE CELL LYMPHOMA; FRONT-LINE TREATMENT AB Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterized by lymphoplasmacytic bone marrow infiltration and immunoglobulin M (IgM) monoclonal gammopathy. It remains incurable, with a median survival of 5-10 years in symptomatic WM. Current first-line treatment options include alkylating agents, nucleoside analogues, and rituximab-based therapies. However, primary or secondary resistance invariably develops. Thus, new treatment options are needed. Preclinical studies have shown that the proteasome inhibitor bortezomib targets signaling pathways of relevance in WM. Bortezomib, alone and in combination with rituximab, has demonstrated notable activity in clinical studies in patients with WM, predominantly in phase II trials in the relapsed or refractory setting. In newly diagnosed patients, bortezomib plus rituximab and dexamethasone is highly active (complete response/near-complete response = 22%). Bortezomib-based therapies result in rapid responses, potentially making them suitable treatment options for patients with hyperviscosity-related symptoms who require a rapid reduction in IgM level. In addition, bortezomib appears unique in reducing rituximab-associated IgM flares. Bortezomib is generally well tolerated in WM. However, neurotoxicity is common and might be the cause of dose reduction or treatment discontinuation. Bortezomib has no adverse effect on stem cell harvesting and engraftment, making it a feasible treatment option in transplantation-eligible patients. These encouraging data have led to the inclusion of bortezomib as a salvage treatment option in the recently updated Fourth International Workshop on Waldenstrom's Macroglobulinemia treatment recommendations. C1 [Dimopoulos, Meletios A.; Kastritis, Efstathios; Gavriatopoulou, Maria] Univ Athens, Sch Med, Alexandra Hosp, Dept Clin Therapeut, GR-11527 Athens, Greece. [Chen, Christine] Princess Margaret Hosp, Dept Haematol Oncol, Toronto, ON M4X 1K9, Canada. [Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RP Dimopoulos, MA (reprint author), Univ Athens, Sch Med, Alexandra Hosp, Dept Clin Therapeut, GR-11527 Athens, Greece. EM mdimop@med.uoa.gr OI Kastritis, Efstathios/0000-0001-8191-5832 FU Millennium Pharmaceuticals, Inc.; Ortho Biotech Products, L. P. FX Drs. Dimopoulos and Treon have received honoraria and/or research grant support for participation in advisory boards of Millennium Pharmaceuticals, Inc. and Ortho Biotech Products, L. P. All other authors report no relevant conflicts of interest. NR 98 TC 10 Z9 12 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 EI 2152-2669 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD APR PY 2010 VL 10 IS 2 BP 110 EP 117 DI 10.3816/CLML.2010.n.015 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 588NF UT WOS:000277077300002 PM 20371443 ER PT J AU Parikh, M Dolson, G Ramanathan, V Sangsiraprapha, W AF Parikh, M. Dolson, G. Ramanathan, V. Sangsiraprapha, W. TI Novel H1N1-associated rhabdomyolysis leading to acute renal failure SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE H1N1; influenza; myositis; renal failure; rhabdomyolysis ID INFLUENZA-B VIRUS; A H1N1; INFECTION; MUSCLE; MYOSITIS AB P>The WHO recently declared that the novel influenza H1N1 virus was responsible for the 2009 flu pandemic. As the virus continues to spread globally and affect more individuals, more complications of infection with this virus are being recognized. To our knowledge, we report the first case of H1N1-induced rhabdomyolysis leading to acute renal failure in an adult. This case highlights the importance of recognizing a significant extrapulmonary complication of H1N1 infection. C1 [Parikh, M.] Baylor Coll Med, Dept Internal Med, Med Residency Off, Houston, TX 77030 USA. [Dolson, G.; Ramanathan, V.; Sangsiraprapha, W.] Houston Vet Affairs Med Ctr, Nephrol Sect, Houston, TX USA. RP Parikh, M (reprint author), Baylor Coll Med, Dept Internal Med, Med Residency Off, 1709 Dryden Suite 500, Houston, TX 77030 USA. EM mrparikh@bcm.tmc.edu; dolson.georgem@med.va.gov NR 13 TC 18 Z9 19 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD APR PY 2010 VL 16 IS 4 BP 330 EP 332 DI 10.1111/j.1469-0691.2010.03185.x PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 564AC UT WOS:000275181700007 PM 20132248 ER PT J AU Pham, PCT Dewar, K Hashmi, S Toscano, E Pham, PMT Pham, PAT Pham, PTT AF Pham, P. C. T. Dewar, K. Hashmi, S. Toscano, E. Pham, P. M. T. Pham, P. A. T. Pham, P. T. T. TI Pain prevalence in patients with chronic kidney disease SO CLINICAL NEPHROLOGY LA English DT Article DE pain; chronic kidney disease ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYCLOOXYGENASE-2 INHIBITORS AB Background: The prevalence of pain in patients with chronic kidney diseases (CKD) is not known. In the current study, we aim to determine the prevalence of pain in CKD patients and its associations with various medical and psychosocial factors. Methods: Consecutive CKD patients who were presented to the renal clinic at Olive View-UCLA Medical Center, a Los Angeles County tertiary referral center, over a 3-month period were interviewed on their medical and psychosocial histories and a history of pain including duration, severity and source. chi(2)-testing for independence and binary logistic regression performed for the presence of pain and CKD stages as well as other medical and psychosocial factors were determined. A separate survey for pain was also done for 100 consecutive non-CKD patients who were presented to our ambulatory medicine clinic for routine care. Results: 54.6% of 130 patients with known CKD interviewed were women. Any type of pain of at least a 2 week duration was reported in 72.9%. The most common source of pain was musculoskeletal. The presence of pain of less than a 2 week duration was associated with worse CKD stages (3 - 5 versus 1 - 2) and non-exercisers. Higher body mass index was associated with having pain lasting longer than a 2 week duration. Among patients who had pain, 33.8% used acetaminophen, 15.4% nonsteroidal anti-inflammatory drugs and 7.8% combination analgesics. In contrast to CKD patients, only 9% of non-CKD patients reported to have any type or duration of pain. Conclusions: Pain was much more prevalent among our CKD compared with non-CKD patients. C1 [Pham, P. C. T.; Dewar, K.; Hashmi, S.; Toscano, E.] Olive View UCLA Med Ctr, Dept Med, Div Nephrol, Sylmar, CA 91342 USA. [Pham, P. M. T.] Greater Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. [Pham, P. A. T.] Mercy Gen Hosp, Sacramento, CA USA. [Pham, P. T. T.] Univ Calif Los Angeles, David Geffen Sch Med, Kidney & Pancreas Transplant Program, Los Angeles, CA 90095 USA. RP Pham, PCT (reprint author), Olive View UCLA Med Ctr, Dept Med, Div Nephrol, 14445 Olive View Dr,2B-182, Sylmar, CA 91342 USA. EM pham.pc@ucla.edu NR 9 TC 7 Z9 7 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD APR PY 2010 VL 73 IS 4 BP 294 EP 299 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 577CB UT WOS:000276197400006 PM 20353737 ER PT J AU Selby, EA Anestis, MD Bender, TW Ribeiro, JD Nock, MK Rudd, MD Bryan, CJ Lim, IC Baker, MT Gutierrez, PM Joiner, TE AF Selby, Edward A. Anestis, Michael D. Bender, Theodore W. Ribeiro, Jessica D. Nock, Matthew K. Rudd, M. David Bryan, Craig J. Lim, Ingrid C. Baker, Monty T. Gutierrez, Peter M. Joiner, Thomas E., Jr. TI Overcoming the fear of lethal injury: Evaluating suicidal behavior in the military through the lens of the Interpersonal-Psychological Theory of Suicide SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE Military; Suicide; Combat; Posttraumatic stress disorder; Injury ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM COMBAT VETERANS; MENTAL-HEALTH PROBLEMS; RISK-FACTORS; WAR VETERANS; ARMED-FORCES; IRAQ WAR; PERCEIVED BURDENSOMENESS; PSYCHIATRIC-DISORDERS; CHILDHOOD ADVERSITY AB Suicide rates have been increasing in military personnel since the start of Operation Enduring Freedom and Operation Iraqi Freedom, and it is vital that efforts be made to advance suicide risk assessment techniques and treatment for members of the military who may be experiencing suicidal symptoms. One potential way to advance the understanding of suicide in the military is through the use of the Interpersonal-Psychological Theory of Suicide. This theory proposes that three necessary factors are needed to complete suicide: feelings that one does not belong with other people, feelings that one is a burden on others or society, and an acquired capability to overcome the fear and pain associated with suicide. This review analyzes the various ways that military service may influence suicidal behavior and integrates these findings into an overall framework with relevant practical implications. Findings suggest that although there are many important factors in military suicide, the acquired capability may be the most impacted by military experience because combat exposure and training may cause habituation to fear of painful experiences, including suicide. Future research directions, ways to enhance risk assessment, and treatment implications are also discussed. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Joiner, Thomas E., Jr.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. [Nock, Matthew K.] Harvard Univ, Cambridge, MA 02138 USA. [Rudd, M. David] Univ Utah, Salt Lake City, UT 84112 USA. [Bryan, Craig J.] Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA. [Baker, Monty T.] San Antonio Mil Med Ctr, Warrior Resiliency Program, San Antonio, TX USA. [Gutierrez, Peter M.] Denver VA Med Ctr, Denver, CO USA. [Gutierrez, Peter M.] Univ Colorado, Denver Sch Med, Boulder, CO 80309 USA. RP Joiner, TE (reprint author), Florida State Univ, Dept Psychol, 1107 W Call St, Tallahassee, FL 32306 USA. EM joiner@psy.fsu.edu OI Bryan, Craig/0000-0002-9714-0733 FU NIMH NIH HHS [F31 MH081396, F31 MH081396-01A2, F31 MH081396-02, F31MH081396] NR 106 TC 56 Z9 59 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD APR PY 2010 VL 30 IS 3 BP 298 EP 307 DI 10.1016/j.cpr.2009.12.004 PG 10 WC Psychology, Clinical SC Psychology GA 572BY UT WOS:000275802700003 PM 20051309 ER PT J AU Kubiak, DW Bryar, JM McDonnell, AM Delgado-Flores, JO Mui, E Baden, LR Marty, FM AF Kubiak, David W. Bryar, Julie M. McDonnell, Anne M. Delgado-Flores, Jorge O. Mui, Emily Baden, Lindsey R. Marty, Francisco M. TI Evaluation of Caspofungin or Micafungin as Empiric Antifungal Therapy in Adult Patients With Persistent Febrile Neutropenia: A Retrospective, Observational, Sequential Cohort Analysis SO CLINICAL THERAPEUTICS LA English DT Article DE echinocandins; caspofungin; micafungin; febrile neutropenia; invasive fungal disease; hematologic malignancy ID LIPOSOMAL AMPHOTERICIN-B; IMMUNOCOMPROMISED PATIENTS; FUNGAL-INFECTIONS; SAFETY; FEVER; CANCER; PHARMACOKINETICS; TRIAL; TOLERABILITY; DEFINITIONS AB Background: Caspofungin is approved in the United States for empiric antifungal therapy for persistent febrile neutropenia (FN). There are limited data about the use of other echinocandins in this setting. Objective: After a formulary change, we retrospectively evaluated the safety and effectiveness of caspofungin and micafungin as empiric antifungal therapy for FN at Brigham and Women's Hospital (Boston, Massachusetts). Methods: This was a retrospective, observational, sequential cohort study. We identified patients who had received doses on concurrent days of either caspofungin (between November 2005 and October 2006) or micafungin (between November 2006 and October 2007) for empiric FN therapy. Patients were included for analysis if they were neutropenic (absolute neutrophil count <500 cells/mu L) and febrile (temperature >= 100.5 degrees F[>= 38 degrees C]). Patients without previous exposure to an echinocandin were included; those included in the caspofungin cohort were excluded from the micafungin cohort. Those who had previously received another systemic antifungal agent for FN therapy (except fluconazole for mucosal candidiasis) were excluded. Patients were followed through hospital discharge. Outcomes analyzed were successful treatment of baseline invasive fungal disease (IFD), incidence of breakthrough IFD, overall mortality, and discontinuation because of adverse events (AEs). IFD was diagnosed and classified according to current European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group criteria. Results: Three hundred twenty-three patients met inclusion criteria (caspofungin, n = 149; micafungin, n = 174). Median age was 49 years in both the caspofungin and micafungin groups; 80 (53.7%) and 99 (56.9%) patients in each group, respectively, were men. Fluconazole prophylaxis had been administered to 30 patients (20.1%) treated with caspofungin and 21 patients (12.1%) treated with micafungin. Caspofungin was administered at 70 mg for one dose, followed by 50 mg daily; micafungin was administered at 100 mg daily. The median duration of therapy and of hospitalization were 10 days and 29 days, respectively, with caspofungin, and 9 days and 28 days with micafungin (both, P = NS between groups). Twelve patients (8.1%) in the caspofungin cohort and 13 (7.5%) in the micafungin cohort died during the study period (P = NS). There were 3 cases (2.0%) of baseline IFD in the caspofungin cohort and 6 (3.4%) in the micafungin cohort (P = NS); 6 were successfully treated (caspofungin, 2 [1.3% of entire group]; micafungin, 4 [2.37% of entire group]; P = NS). Breakthrough IFD was diagnosed in 16 patients (10.7%) receiving caspofungin and 21 (12.1%) receiving micafungin (P = NS). AEs requiring echinocandin discontinuation were uncommon (caspofungin, 2 cases of rash and 1 anaphylactoid infusion reaction [2.0%]; mica-fungin, 1 liver function test elevation times the upper limit of normal and 1 maculopapular rash [1.1%]; P = NS). Conclusion: Micafungin, as empiric antifungal therapy for persistent FN, did not appear to differ significantly from caspofungin in terms of safety profile or efficacy in the adult patients included in this sequential cohort analysis at one institution. ClinicalTrials.gov identifier: NCT00723073. (Clin Ther. 2010;32:637-648) (C) 2010 Excerpta Medica Inc. C1 [Kubiak, David W.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Bryar, Julie M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Baden, Lindsey R.; Marty, Francisco M.] Harvard Univ, Sch Med, Boston, MA USA. [Baden, Lindsey R.; Marty, Francisco M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kubiak, DW (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB A4, Boston, MA 02115 USA. EM dwkubiak@partners.org FU Astellas Pharma US; Cubist Pharmaceuticals, Inc; Basilea Pharmaceutica; Schering-Plough Research Institute FX Financial support for this investigator-initiated study and the production costs for the preparation and publication of this article were provided by Astellas Pharma US. The sponsor was not involved in the study design, conduct, analysis, or writing of this article.; Dr. Kubiak has received research support from Astellas Pharma US and Cubist Pharmaceuticals, Inc. Dr. Marty has received research grant support from Astellas Pharma US, Basilea Pharmaceutica, and Schering-Plough Research Institute, and consulting honoraria from Basilea Pharmaceutica.; The authors have indicated that they have no other conflicts of interest regarding the content of this article. NR 27 TC 31 Z9 33 U1 2 U2 5 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD APR PY 2010 VL 32 IS 4 BP 637 EP 648 DI 10.1016/j.clinthera.2010.04.005 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 593UM UT WOS:000277486600003 PM 20435233 ER PT J AU Hickman, SE El Khoury, J AF Hickman, Suzanne E. El Khoury, Joseph TI Mechanisms of Mononuclear Phagocyte Recruitment in Alzheimer's Disease SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Microglia; mononuclear phagocytes; Alzheimer's disease; chemokines ID MARROW-DERIVED MICROGLIA; CENTRAL-NERVOUS-SYSTEM; MONOCYTE CHEMOATTRACTANT PROTEIN-1; BONE-MARROW; CRYPTOCOCCUS-NEOFORMANS; HEMATOPOIETIC-CELLS; REACTIVE MICROGLIA; AMYLOID PLAQUES; TRANSGENIC MICE; BRAIN AB Alzheimer's disease (AD) is associated with a significant neuroinflammatory component. Mononuclear phagocytes including monocytes and microglia are the principal cells involved, and they accumulate at perivascular sites of beta-amyloid (A beta) deposition and in senile plaques. Recent evidence suggests that mononuclear phagocyte accumulation in the AD brain is dependent on chemokines. CCL2, a major monocyte chemokine, is upregulated in the AD brain. Interaction of CCL2 with its receptor CCR2 regulates mononuclear phagocyte accumulation in a mouse model of AD. CCR2 deficiency leads to lower mononuclear phagocyte accumulation and is associated with higher brain A beta levels, specifically around blood vessels, suggesting that monocytes accumulate at sites of A beta deposition in an initial attempt to clear these deposits and stop or delay their neurotoxic effects. Indeed, enhancing mononuclear phagocyte accumulation delays progression of AD. Here we review the mechanisms of mononuclear phagocyte accumulation in AD and discuss the potential roles of additional chemokines and their receptors in this process. We also propose a multi-step model for recruitment of mononuclear phagocytes into the brain. The first step involves egress of monocyte/microglial precursors from the bone marrow into the blood. The second step is crossing the blood-brain barrier to the perivascular areas and into the brain parenchyma. The final step includes movement of monocytes/microglia from areas of the brain that lack any amyloid deposition to senile plaques. Understanding the mechanism of recruitment of mononuclear phagocytes to the AD brain is necessary to further understand the role of these cells in the pathogenesis of AD and to identify any potential therapeutic use of these cells for the treatment of this disease. C1 [El Khoury, Joseph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Infect Dis, Charlestown, MA 02129 USA. RP El Khoury, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Infect Dis, CNY 149,Room 8301,149 13th St, Charlestown, MA 02129 USA. EM jelkhoury@partners.org FU NINDS [NS 059005]; Dana Foundation FX This work was supported by NINDS grant NS 059005 (JEK) and a grant from the Dana Foundation Neuro-Immunology program (JEK). NR 60 TC 45 Z9 45 U1 1 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PD APR PY 2010 VL 9 IS 2 BP 168 EP 173 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 573UM UT WOS:000275940500007 PM 20205643 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI One Size Fits None? Treatment Algorithms and Guidelines in Psychiatry and Neurology SO CNS SPECTRUMS LA English DT Editorial Material C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD APR PY 2010 VL 15 IS 4 BP 210 EP 211 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 587BA UT WOS:000276960400001 PM 20414169 ER PT J AU Ditman, T Brunye, TT Mahoney, CR Taylor, HA AF Ditman, Tali Brunye, Tad T. Mahoney, Caroline R. Taylor, Holly A. TI Simulating an enactment effect: Pronouns guide action simulation during narrative comprehension SO COGNITION LA English DT Article DE Perspective-taking; Embodied cognition; Discourse comprehension; Language; Action understanding ID LANGUAGE COMPREHENSION; SITUATION MODELS; PERSPECTIVE-TAKING; MOTOR RESONANCE; MEMORY; INFORMATION; REPRESENTATIONS; ACCESSIBILITY; CONSTRUCTION; OBJECTS AB Recent research has suggested that reading involves the mental simulation of events and actions described in a text. It is possible however that previous findings did not tap into processes engaged during natural reading but rather those triggered by task demands. The present study examined whether readers spontaneously mentally simulate the actions described in simple narratives by using a memory task that did not encourage the formation of mental images. During encoding, participants read event scenarios preceded by 'I', 'You', or 'He', and then 10 min (Experiment 1) or 3 days later (Experiment 2), we examined memory for action and descriptive elements of these scenarios. Given previous research demonstrating that readers simulate described actions preceded by 'You' from an actor's perspective, we predicted that such action statements would be better remembered than those preceded by 'He' or 'I' a simulated enactment effect. Results of both experiments supported this prediction; readers had better memory for actions but not descriptive information (10 min and 3 days later) after reading statements preceded by 'You'. Results demonstrate that readers spontaneously mentally simulate actions during language comprehension and take different mental perspectives, even when doing so is not necessary to perform the task. (C) 2009 Elsevier B.V. All rights reserved. C1 [Ditman, Tali; Brunye, Tad T.; Mahoney, Caroline R.; Taylor, Holly A.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Ditman, Tali] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Brunye, Tad T.; Mahoney, Caroline R.] USA, NSRDEC, Natick, MA 01760 USA. RP Ditman, T (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM tali.ditman@tufts.edu RI 江, 鈺麒/G-1379-2014 NR 53 TC 28 Z9 29 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD APR PY 2010 VL 115 IS 1 BP 172 EP 178 DI 10.1016/j.cognition.2009.10.014 PG 7 WC Psychology, Experimental SC Psychology GA 576EF UT WOS:000276126400017 PM 19939357 ER PT J AU Gros, DF Gros, KS Simms, LJ AF Gros, Daniel F. Gros, Kirstin Stauffacher Simms, Leonard J. TI Relations Between Anxiety Symptoms and Relational Aggression and Victimization in Emerging Adults SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Social anxiety; Cognitive anxiety; Somatic anxiety; Relational aggression; Relational victimization ID SOCIAL-PSYCHOLOGICAL ADJUSTMENT; NATIONAL-COMORBIDITY-SURVEY; STATE-TRAIT INVENTORY; QUALITY-OF-LIFE; PEER VICTIMIZATION; PHYSICAL AGGRESSION; COLLEGE-STUDENTS; PSYCHOMETRIC PROPERTIES; SOMATIC COMPLAINTS; COMMUNITY SAMPLE AB Although it has been suggested that relational aggression (RA) and relational victimization (RV) are associated with elevated rates of social anxiety (SA), the nature of how these behaviors relate to the symptom development of SA has not yet been explored. In the present study, we investigated the relations between the symptoms of SA and general anxiety and RA and RV in a questionnaire study of 315 emerging adults. To identify the unique predictive power of RA/RV, a series of hierarchical regression analyses were conducted, controlling for gender, age, and physical aggression and victimization. All symptoms of anxiety were uniquely and positively predicted by RA; however, only symptoms of cognitive and somatic anxiety were predicted positively and uniquely by RV. These findings further elucidate the linkage between RA and anxiety in early adulthood, serving to highlight the importance of considering lifetime social history when investigating anxiety and aggression and victimization behaviors. C1 [Gros, Daniel F.] Ralph H Johnson Vet Adm Med Ctr, Mental Hlth Serv, Charleston, SC 29410 USA. [Gros, Daniel F.; Gros, Kirstin Stauffacher] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Simms, Leonard J.] SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. RP Gros, DF (reprint author), Ralph H Johnson Vet Adm Med Ctr, Mental Hlth Serv, Charleston, SC 29410 USA. EM grosd@musc.edu NR 64 TC 9 Z9 9 U1 2 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD APR PY 2010 VL 34 IS 2 BP 134 EP 143 DI 10.1007/s10608-009-9236-z PG 10 WC Psychology, Clinical SC Psychology GA 567ES UT WOS:000275426600004 ER PT J AU Wucherpfennig, KW Gagnon, E Call, MJ Huseby, ES Call, ME AF Wucherpfennig, Kai W. Gagnon, Etienne Call, Melissa J. Huseby, Eric S. Call, Matthew E. TI Structural Biology of the T-cell Receptor: Insights into Receptor Assembly, Ligand Recognition, and Initiation of Signaling SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID ACTIVATING IMMUNE RECEPTORS; ANTIGEN RECEPTOR; ALPHA-BETA; CRYSTAL-STRUCTURE; TCR/CD3 COMPLEX; CLASS-I; CD3-EPSILON-GAMMA HETERODIMER; THYMIC SELECTION; MOLECULAR-BASIS; CD3 COMPLEX AB The T-cell receptor (TCR)-CD3 complex serves as a central paradigm for general principles of receptor assembly, ligand recognition, and signaling in the immune system. There is no other receptor system that matches the diversity of both receptor and ligand components. The recent expansion of the immunological structural database is beginning to identify key principles of MHC and peptide recognition. The multicomponent assembly of the TCR complex illustrates general principles used by many receptors in the immune system, which rely on basic and acidic transmembrane residues to guide assembly. The intrinsic binding of the cytoplasmic domains of the CD3 epsilon and zeta chains to the inner leaflet of the plasma membrane represents a novel mechanism for control of receptor activation: Insertion of critical CD3 epsilon tyrosines into the hydrophobic membrane core prevents their phosphorylation before receptor engagement. C1 [Wucherpfennig, Kai W.; Gagnon, Etienne; Call, Melissa J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. [Huseby, Eric S.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. [Call, Matthew E.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu OI Call, Matthew/0000-0001-5846-6469 FU National Institutes of Health [RO1 AI054520, AI064177]; Beckman Young Investigator and Searle Scholar awards FX This work was supported by grants to K.W.W. to the National Institutes of Health (RO1 AI054520 and AI064177). E.S.H. was supported in part by Beckman Young Investigator and Searle Scholar awards. NR 74 TC 37 Z9 39 U1 0 U2 18 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD APR PY 2010 VL 2 IS 4 AR a005140 DI 10.1101/cshperspect.a005140 PG 14 WC Cell Biology SC Cell Biology GA 625GF UT WOS:000279882300014 PM 20452950 ER PT J AU Jakobiec, FA Mehta, M Greenstein, SH Colby, K AF Jakobiec, Frederick A. Mehta, Manisha Greenstein, Scott H. Colby, Kathryn TI The White Caruncle: Sign of a Keratinous Cyst Arising From a Sebaceous Gland Duct SO CORNEA LA English DT Article DE caruncle; cyst; keratin; white; eyelids ID STEATOCYSTOMA SIMPLEX; LESIONS AB Purpose: To describe an acquired, smooth white lesion of the caruncle and to underscore the role of subsurface keratinizing squamous epithelium in its formation. Methods: Clinical photographic documentation, histopathologic evaluation, and immunohistochemical staining of an excised specimen from a 25-year-old woman. Results: A cyst was found that was lined by keratinizing squamous epithelium without a keratohyaline layer (trichilemmal keratinization), typical of lesions of the pilosebaceous unit. A portion of the cyst's lining was replaced by granulomatous inflammation resulting from an earlier spontaneous partial rupture. Ki-67 immunolabeling demonstrated relatively few nuclei in S-phase (DNA synthesis) in comparison with the overlying epithelium, thereby suggesting an obstructive, nonproliferative cause for the cyst. Conclusion: A white caruncular lesion is a very rare finding according to the literature. It is most likely caused by a cyst lined by squamous epithelium elaborating trichilemmal-type keratin. A sebaceous gland duct was established as the source for the current lesion. C1 [Jakobiec, Frederick A.; Mehta, Manisha] Harvard Univ, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Sch Med, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Mehta, Manisha; Greenstein, Scott H.; Colby, Kathryn] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med, Boston, MA 02114 USA. [Greenstein, Scott H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Comprehens Ophthalmol Serv, Sch Med, Boston, MA 02114 USA. [Colby, Kathryn] Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea Serv, Sch Med, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 18 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD APR PY 2010 VL 29 IS 4 BP 453 EP 455 DI 10.1097/ICO.0b013e3181b55b5c PG 3 WC Ophthalmology SC Ophthalmology GA 576RG UT WOS:000276164400017 PM 20164755 ER PT J AU Grover, S Jacobs, DS Colby, KA AF Grover, Surbhi Jacobs, Deborah S. Colby, Kathryn A. TI Boston Ocular Surface Prosthesis for Persistent Epitheliopathy After Treatment of Conjunctival Melanoma SO CORNEA LA English DT Article DE conjunctival melanoma; primary acquired melanosis; limbal stem cells; epithelial dysfunction; Boston Ocular Surface Prosthesis; scleral lens; mitomycin C; cryotherapy ID PRIMARY ACQUIRED MELANOSIS; STEM-CELL DEFICIENCY; TOPICAL MITOMYCIN-C; RISK AB Purpose: To report two cases of persistent epitheliopathy after treatment of conjunctival melanoma and review management options for this condition. Methods: Case report and literature review. Results: Persistent epitheliopathy, presumably resulting from limbal stem cell deficiency, is an uncommon complication of treatment of conjunctival malignant melanoma with surgical excision, cryotherapy, and mitomycin C. The Boston Ocular Surface Prosthesis was successful in improving vision, comfort, and epithelial status in our patients. Conclusion: Persistent epitheliopathy is a rare complication of treatment of conjunctival melanoma. The Boston Ocular Surface Prosthesis is a viable treatment option in this situation. C1 [Jacobs, Deborah S.; Colby, Kathryn A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Grover, Surbhi; Jacobs, Deborah S.; Colby, Kathryn A.] Harvard Univ, Sch Med, Boston, MA USA. RP Colby, KA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM kacolby@meei.harvard.edu NR 17 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD APR PY 2010 VL 29 IS 4 BP 459 EP 461 DI 10.1097/ICO.0b013e3181b55b40 PG 3 WC Ophthalmology SC Ophthalmology GA 576RG UT WOS:000276164400019 PM 20164756 ER PT J AU Addis, DR Leclerc, CM Muscatell, KA Kensinger, EA AF Addis, Donna R. Leclerc, Christina M. Muscatell, Keely A. Kensinger, Elizabeth A. TI There are age-related changes in neural connectivity during the encoding of positive, but not negative, information SO CORTEX LA English DT Article DE Aging; Connectivity; Emotion; fMRI; Memory; Structural equation modeling ID EMOTIONAL MEMORY; PREFRONTAL CORTEX; BRAIN ACTIVATION; YOUNGER ADULTS; OLDER-ADULTS; AMYGDALA; COGNITION; MECHANISMS; EXPERIENCE; NETWORK AB Introduction: Older adults often show sustained attention toward positive information and an improved memory for positive events. Little is known about the neural changes that may underlie these effects, although recent research has suggested that older adults may show differential recruitment of prefrontal regions during the successful encoding of emotional information. in the present study, effective connectivity analyses examined the network of regions that college-age and older adults recruited during the encoding of positive and negative images. Methods: Participants viewed positive and negative images while undergoing a functional magnetic resonance imaging (fMRI) scan. Structural equation modeling was used to compare young and older adults' connectivity among regions of the emotional memory network while they encoded negative or positive items. Results: Aging did not impact the connectivity among regions engaged during the encoding of negative information, but age differences did arise during the encoding of positive information. Most notably, in older adults, the ventromedial prefrontal cortex and amygdala strongly influenced hippocampal activity during the encoding of positive information. By contrast, in young adults, a strong thalamic influence on hippocampal activity was evident during encoding. Conclusions: These findings suggest that older adults' "positivity effect" may arise from age-related changes in the interactions between affect-processing regions and the hippocampus during the encoding of positive information. (C) 2009 Elsevier Srl. All rights reserved. C1 [Leclerc, Christina M.; Muscatell, Keely A.; Kensinger, Elizabeth A.] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. [Addis, Donna R.] Univ Auckland, Dept Psychol, Auckland 1, New Zealand. [Kensinger, Elizabeth A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Kensinger, EA (reprint author), Boston Coll, Dept Psychol, 140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM elizabeth.kensinger@bc.edu OI Addis, Donna Rose/0000-0002-6231-1491 FU National Institutes of Health [MH080833]; Searle Scholars program FX This research was supported by grants from the National Institutes of Health (MH080833) and the Searle Scholars program (to E.A.K.). The authors thank Lisa Feldman Barrett, Angela Gutchess, Heathery Urry, Robert Waldinger, and Chris Wright for helpful discussion. NR 49 TC 41 Z9 43 U1 4 U2 17 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD APR PY 2010 VL 46 IS 4 SI SI BP 425 EP 433 DI 10.1016/j.cortex.2009.04.011 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 572BA UT WOS:000275800000002 PM 19555933 ER PT J AU Leshikar, ED Gutchess, AH Hebrank, AC Sutton, BP Park, DC AF Leshikar, Eric D. Gutchess, Angela H. Hebrank, Andrew C. Sutton, Bradley P. Park, Denise C. TI The impact of increased relational encoding demands on frontal and hippocampal function in older adults SO CORTEX LA English DT Article DE Aging; Relational memory; Prefrontal cortex; Hippocampus; Encoding ID MEDIAL TEMPORAL-LOBE; AGE-RELATED DIFFERENCES; LONG-TERM-MEMORY; WORKING-MEMORY; COGNITIVE CONTROL; EPISODIC MEMORY; DEFAULT NETWORK; LIFE-SPAN; ASSOCIATIONS; RETRIEVAL AB In the present study, we manipulated the cognitive effort in an associative encoding task using functional magnetic resonance imaging (fMRI). Older and younger adults were presented with two objects that were either semantically related or unrelated, and were required to form a relationship between the items. Both groups self-reported greater difficulty in completing the unrelated associative encoding task providing independent evidence of the associative difficulty manipulation. on both the low and high difficulty tasks, older adults showed a typical pattern of increased right inferior frontal recruitment relative to younger adults. Of particular interest was the finding that both groups showed increased activation as task difficulty increased in the left inferior frontal gyrus and left hippocampus. Overall, the results suggest that the aging brain is characterized by greater prefrontal processing, but that as cognitive demand increases, the networks used by older and younger adults are the largely the same. (C) 2009 Elsevier Srl. All rights reserved. C1 [Park, Denise C.] Univ Texas Dallas, Ctr Brain Hlth, Dallas, TX 75235 USA. [Leshikar, Eric D.; Sutton, Bradley P.] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA. [Gutchess, Angela H.] Brandeis Univ, Dept Psychol, Cambridge, MA USA. [Gutchess, Angela H.] Massachusetts Gen Hosp, Cambridge, MA USA. [Sutton, Bradley P.] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. RP Park, DC (reprint author), Univ Texas Dallas, Ctr Brain Hlth, 2200 W Mockingbird Lane, Dallas, TX 75235 USA. EM denise@utdallas.edu RI Sutton, Bradley/A-4801-2008 OI Sutton, Bradley/0000-0002-8443-0408 FU National Institute on Aging [R-37-AGO-06265-26]; National institute of Mental Health [T32 MH19554] FX This research was supported by National Institute on Aging grant Project R-37-AGO-06265-26 awarded to Denise C. Park. Eric D. Leshikar was supported by the National institute of Mental Health training grant T32 MH19554. The authors gratefully acknowledge the various contributions of Brian Gonsalves, Robert Welsh, Lucas Jenkins, and Josh Goh in this project. NR 51 TC 32 Z9 32 U1 1 U2 13 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD APR PY 2010 VL 46 IS 4 SI SI BP 507 EP 521 DI 10.1016/j.cortex.2009.07.011 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 572BA UT WOS:000275800000009 PM 19709652 ER PT J AU Vernon, C LeTourneau, JL AF Vernon, Christopher LeTourneau, Jennifer L. TI Lactic Acidosis: Recognition, Kinetics, and Associated Prognosis SO CRITICAL CARE CLINICS LA English DT Article DE Lactic acidosis; Mitochondria; Prognosis; Critical care; Shock; Metabolic diseases ID PROPOFOL INFUSION SYNDROME; CONTROLLED CLINICAL-TRIAL; BLOOD LACTATE LEVELS; SHORT-BOWEL SYNDROME; ACUTE LIVER-FAILURE; MITOCHONDRIAL RESPIRATORY-CHAIN; PYRUVATE-CARBOXYLASE DEFICIENCY; PROPYLENE-GLYCOL TOXICITY; CRITICALLY-ILL PATIENTS; HIV-INFECTED PATIENTS AB Lactic acidosis is a common condition encountered by critical care providers. Elevated lactate and decreased lactate clearance are important for prognostication. Not all lactate in the intensive care unit is due to tissue hypoxia or ischemia and other sources should be evaluated. Lactate, in and of itself, is unlikely to be harmful and is a preferred fuel for many cells. Treatment of lactic acidosis continues to be aimed the underlying source. C1 [LeTourneau, Jennifer L.] Portland VA Med Ctr, Pulm Dis Sect, Portland, OR 97239 USA. [Vernon, Christopher] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97239 USA. RP LeTourneau, JL (reprint author), Portland VA Med Ctr, Pulm Dis Sect, 3710 SW US Vet Hosp Rd,Mailcode P3PULM, Portland, OR 97239 USA. EM Jennifer.Letourneau@va.gov RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 219 TC 35 Z9 38 U1 2 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0704 J9 CRIT CARE CLIN JI Crit. Care Clin. PD APR PY 2010 VL 26 IS 2 BP 255 EP + DI 10.1016/j.ccc.2009.12.007 PG 30 WC Critical Care Medicine SC General & Internal Medicine GA 590AB UT WOS:000277194400003 PM 20381719 ER PT J AU Rello, J Afessa, B Anzueto, A Arroliga, AC Olson, ME Restrepo, MI Talsma, SS Bracken, RL Kollef, MH AF Rello, Jordi Afessa, Bekele Anzueto, Antonio Arroliga, Alejandro C. Olson, Merle E. Restrepo, Marcos I. Talsma, Silke S. Bracken, Ronald L. Kollef, Marin H. TI Activity of a silver-coated endotracheal tube in preclinical models of ventilator-associated pneumonia and a study after extubation SO CRITICAL CARE MEDICINE LA English DT Article DE biocompatible coated materials; endotracheal intubation; nosocomial infections; ventilator-associated pneumonia; silver ID IN-VITRO; PSEUDOMONAS-AERUGINOSA; BACTERIAL-COLONIZATION; BIOFILM FORMATION; MICROBIAL COLONIZATION; ADHESION; BIOMATERIALS; CATHETERS; ADHERENCE; SURFACES AB Objective: To elucidate the mechanism of action of the silver-coated endotracheal tube in models of the early pathogenesis of ventilator-associated pneumonia. Design: Open-labeled, prospective, controlled, sequentially conducted, preclinical studies, and in vitro assessment of tubes from patients. Setting: Microbiology laboratory of a device manufacturer, animal research facility of a university, and a tertiary medical center. Interventions: Endotracheal tubes were similar except for the silver coating. In the 21-day in vitro elution model, tube samples were incubated in saline solution at 37.8 degrees C. In the in vitro adherence model, coated and uncoated tubes were exposed to 21 respiratory isolates of radiolabeled microorganisms for 2-4 hrs. In the animal model, 12 healthy white rabbits were intubated for 16 hrs with noncuffed silver-coated or uncoated tubes and challenged with buccal administration of Pseudomonas aeruginosa. In the in vitro assessment, tubes from 16 patients underwent quantitative culture assessment and qualitative confocal laser scanning microscopy. Measurements and Main Results: After in vitro incubation, the mean residual silver concentration was 2.6 mu g/cm(2), confirming that the coating was not entirely depleted. In vitro adherence to the silver-coated endotracheal tube was less than that of the uncoated tube for 12 of 21 isolates and equivalent for seven. For example, adherence to the silver-coated endotracheal tube was reduced >90% for all five isolates of P. aeruginosa (p < .05). In rabbits, P. aeruginosa colonization on the silver-coated endotracheal tube was reduced 99.9% compared with that on the uncoated tube (p < .0001); colonization in the tracheal and lung tissue was reduced >99% (p < .05). In the in vitro assessment, pathogens were detected on none of nine silver-coated tubes from patients and three of seven control tubes (p > .05). Conclusions: The collective findings of this series of studies demonstrated that the silver-coated endotracheal tube was active in models designed to mimic the early pathogenesis of ventilator-associated pneumonia. (Crit Care Med 2010; 38: 1135-1140) C1 [Rello, Jordi] Univ Rovira & Virgili, Joan XXIII Univ Hosp, CIBER Enfermedades Resp CIBERes, IISPV, Tarragona, Spain. [Afessa, Bekele] Mayo Clin, Coll Med, Rochester, MN USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Univ Hosp, S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Arroliga, Alejandro C.] Scott & White Mem Hosp & Clin, Temple, TX USA. [Arroliga, Alejandro C.] Texas A&M Hlth Sci Ctr, Coll Med, Temple, TX USA. [Olson, Merle E.] Innovotech Inc, Edmonton, AB, Canada. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, VERDICT S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Talsma, Silke S.] Bard Med Div, Covington, GA USA. [Bracken, Ronald L.] CR Bard Inc, Covington, GA USA. [Kollef, Marin H.] Washington Univ, Sch Med, St Louis, MO USA. RP Rello, J (reprint author), Univ Rovira & Virgili, Joan XXIII Univ Hosp, CIBER Enfermedades Resp CIBERes, IISPV, Tarragona, Spain. EM jrello.hj23.ics@gencat.cat RI Restrepo, Marcos/H-4442-2014; OI Olson, Merle/0000-0003-3654-7692; Rello, Jordi/0000-0003-0676-6210 FU C. R. Bard, Inc.; University of Calgary, Alberta, Canada; Mayo Clinic College of Medicine, Rochester, MN FX Supported by grants from C. R. Bard, Inc., and performed at the University of Calgary, Alberta, Canada; C. R. Bard, Inc., Covington, GA; and Mayo Clinic College of Medicine, Rochester, MN. NR 31 TC 17 Z9 19 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2010 VL 38 IS 4 BP 1135 EP 1140 DI 10.1097/CCM.0b013e3181cd12b8 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 581CW UT WOS:000276499700015 PM 20081533 ER PT J AU Hamdy, O Zwiefelhofer, D AF Hamdy, Osama Zwiefelhofer, Debbie TI Weight Management Using a Meal Replacement Strategy in Type 2 Diabetes SO CURRENT DIABETES REPORTS LA English DT Article DE Meal replacement; Weight management; Type 2 diabetes ID LIFE-STYLE MODIFICATION; LOW-FAT DIET; INSULIN-RESISTANCE; OBESE SUBJECTS; ADULTS; TRIAL; RISK; INDIVIDUALS; PREVALENCE; PROTEIN AB The growing prevalence of diabetes parallels the increased prevalence of obesity. Overweight and obese individuals with diabetes who attempt weight reduction face considerable challenges. However, several recent studies showed that weight reduction in patients with diabetes is feasible using a multidisciplinary approach that incorporates structured dietary intervention and meal replacements (MRs). Nutritionally complete MRs are shown to be useful at the start of weight reduction programs and for weight maintenance because of their nutrition adequacy. However, patients using this approach need to monitor their blood glucose levels closely and may need to adjust their diabetes medications. Most commercial MRs are currently fortified with vitamins and minerals to prevent long-term deficiency in essential micronutrients that are commonly seen in low-calorie diet plans. They also come in different flavors and formats that improve their general acceptability. To successfully initiate weight loss, MRs are generally used as absolute replacement of an agreed upon number of meals/snacks. This article covers the use of MRs for patients with diabetes for short-term and long-term weight reduction in clinical trials and real-world clinical practice. C1 [Hamdy, Osama] Joslin Diabet Ctr, Boston, MA USA. [Zwiefelhofer, Debbie] Nestle HealthCare Nutr, Minnetonka, MN 55343 USA. RP Hamdy, O (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA USA. EM Osama.Hamdy@joslin.harvard.edu; dzwiefel@comcast.net NR 27 TC 9 Z9 10 U1 1 U2 6 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD APR PY 2010 VL 10 IS 2 BP 159 EP 164 DI 10.1007/s11892-010-0103-9 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 571WM UT WOS:000275786600011 PM 20425576 ER PT J AU Motyckova, G Stone, RM AF Motyckova, Gabriela Stone, Richard M. TI The Role of Molecular Tests in Acute Myelogenous Leukemia Treatment Decisions SO CURRENT HEMATOLOGIC MALIGNANCY REPORTS LA English DT Article DE Acute myeloid leukemia; Genetics; Prognosis; FLT3; NPM1 AB The prognosis for patients with acute myelogenous leukemia (AML) is dependent on age, karyotype, and the genetics of the neoplastic cell. The molecular markers with prognostic impact include mutations in FLT3, NPM1, MLL, WT1, c-KIT, and expression levels of BAALC, NM1, ERG, and CXCR4. Gene expression profiles and microRNA expression patterns in AML may prove highly useful in defining the prognosis of AML. Cytogenetic and, increasingly, molecular findings are used in determining the best therapy for AML patients, especially the choice of whether to perform allogeneic stem cell transplantation. C1 [Motyckova, Gabriela; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Motyckova, G (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM gmotyckova@partners.org; rstone@partners.org NR 55 TC 15 Z9 17 U1 0 U2 1 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1558-8211 J9 CURR HEMATOL MALIG R JI Curr. Hematol. Malig. Rep. PD APR PY 2010 VL 5 IS 2 BP 109 EP 117 DI 10.1007/s11899-010-0049-7 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA V25PJ UT WOS:000208489600008 PM 20425404 ER PT J AU Baz-Hecht, M Goldfine, AB AF Baz-Hecht, Merav Goldfine, Allison B. TI The impact of vitamin D deficiency on diabetes and cardiovascular risk SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE cardiovascular risk/disease; diabetes; vitamin D ID NUTRITION EXAMINATION SURVEY; RENIN-ANGIOTENSIN SYSTEM; 3RD NATIONAL-HEALTH; 25-HYDROXYVITAMIN D DEFICIENCY; PARATHYROID-HORMONE LEVELS; NURSING-HOME RESIDENTS; CORONARY-HEART-DISEASE; SMOOTH-MUSCLE-CELLS; MIDDLE-AGED MEN; BODY-MASS INDEX AB Purpose of review To review the association between vitamin D deficiency and diabetes and cardiovascular risk. Recent findings Vitamin D deficiency is newly recognized as a common condition of increasing prevalence worldwide. Clinically, vitamin D has an established role in calcium and bone metabolism and has recently been shown to be associated with increased risk of developing type 1 and type 2 diabetes mellitus and cardiovascular disease (CVD), as well as with cardiovascular risk factors such as hypertension and obesity. The molecular mechanisms of these associations remain incompletely understood. The active metabolite of vitamin D regulates transcription of multiple gene products with antiproliferative, prodifferentiative, and immunomodulatory effects. Although vitamin D deficiency is frequently unrecognized clinically, laboratory measurement is easy to perform and treatment of vitamin D deficiency is relatively well tolerated and inexpensive. Limited, yet promising, results of proof-of-concept intervention studies of using vitamin D in diabetes will be presented. Summary The high prevalence of vitamin D deficiency and plausible molecular mechanisms linking this to diabetes and cardiovascular risk suggest treatment of vitamin D deficiency to prevent and/or treat diabetes is a promising field to explore. C1 [Baz-Hecht, Merav; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Baz-Hecht, Merav; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU Eleanor and Miles Shore 50th Anniversary Fellowship; William Randolph Hearst Fellowship Foundation; American Diabetes Association [06-CD-07] FX This work was sponsored by The Eleanor and Miles Shore 50th Anniversary Fellowship Award and The William Randolph Hearst Fellowship Foundation (M.B.H.) and the American Diabetes Association 06-CD-07 (A.B.G.). NR 85 TC 58 Z9 61 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD APR PY 2010 VL 17 IS 2 BP 113 EP 119 DI 10.1097/MED.0b013e3283372859 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691EJ UT WOS:000285062800002 PM 20150805 ER PT J AU Cypess, AM Kahn, CR AF Cypess, Aaron M. Kahn, C. Ronald TI Brown fat as a therapy for obesity and diabetes SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE adult humans; antiobesity therapy; brown adipose tissue; clinical and basic science research; PET/CT ID BETA(3)-ADRENERGIC RECEPTOR AGONIST; BONE MORPHOGENETIC PROTEIN-7; DIET-INDUCED OBESITY; ADIPOSE-TISSUE; ENERGY-EXPENDITURE; WHITE ADIPOSE; ADULT HUMANS; PREADIPOCYTE DIFFERENTIATION; NONSHIVERING THERMOGENESIS; ADIPOCYTE DIFFERENTIATION AB Purpose of review Human fat consists of white and brown adipose tissue (WAT and BAT). Though most fat is energy-storing WAT, the thermogenic capacity of even small amounts of BAT makes it an attractive therapeutic target for inducing weight loss through energy expenditure. This review evaluates the recent discoveries regarding the identification of functional BAT in adult humans and its potential as a therapy for obesity and diabetes. Recent findings Over the past year, several independent research teams used a combination of positron-emission tomography and computed tomography (PET/CT) imaging, immunohistochemistry, and gene and protein expression assays to prove conclusively that adult humans have functional BAT. This has occurred against a backdrop of basic studies defining the origins of BAT, new components of its transcriptional regulation, and the role of hormones in stimulation of BAT growth and differentiation. Summary Adult humans have functional BAT, a new target for antiobesity and antidiabetes therapies focusing on increasing energy expenditure. Future studies will refine the methodologies used to measure BAT mass and activity, expand our knowledge of critical-control points in BAT regulation, and focus on testing pharmacological agents that increase BAT thermogenesis and help achieve long-lasting weight loss and an improved metabolic profile. C1 [Cypess, Aaron M.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu FU Eli Lilly Foundation; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK082659, DK046200, DK081604, DK087317, RR025757, P30 DK036836] FX This work was supported in part by the Eli Lilly Foundation and NIH grants DK082659 (C.R.K), DK046200, DK081604, DK087317, RR025757 (A.M.C.), and P30 DK036836 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National NIDDK or the NIH. NR 73 TC 99 Z9 109 U1 5 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD APR PY 2010 VL 17 IS 2 BP 143 EP 149 DI 10.1097/MED.0b013e328337a81f PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691EJ UT WOS:000285062800006 PM 20160646 ER PT J AU Paro, R Lee, JT AF Paro, Renato Lee, Jeannie T. TI Extending the frontiers of epigenetic regulation Editorial overview SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Editorial Material C1 [Paro, Renato] ETH, D BSSE, CH-4058 Basel, Switzerland. [Lee, Jeannie T.] Howard Hughes Med Inst, Dept Mol Biol, Chevy Chase, MD USA. [Lee, Jeannie T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA. RP Paro, R (reprint author), ETH, D BSSE, Mattenstr 26, CH-4058 Basel, Switzerland. EM renato.paro@bsse.ethz.ch; lee@molbio.mgh.harvard.edu NR 0 TC 3 Z9 3 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2010 VL 20 IS 2 BP 107 EP 109 DI 10.1016/j.gde.2010.03.011 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 601ON UT WOS:000278071700001 PM 20382521 ER PT J AU Yoshida, T Ng, SYM Georgopoulos, K AF Yoshida, Toshimi Ng, Samuel Yao-Ming Georgopoulos, Katia TI Awakening lineage potential by Ikaros-mediated transcriptional priming SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID COMMON LYMPHOID PROGENITORS; CELL SELF-RENEWAL; STEM-CELLS; B-CELL; MULTIPOTENT PROGENITORS; COMMITMENT; FETAL; DIFFERENTIATION; IDENTIFICATION; SPECIFICATION AB Bioinformatic studies on a revised hierarchy of hematopoietic progenitors have provided a genome-wide view of lineage-affiliated transcriptional programs directing early hematopoiesis. Unexpectedly, lymphoid, myeloid, and erythroid gene expression programs were primed with similar frequency at the multipotent progenitor stage indicating a stochastic nature to this process. Multi lineage transcriptional priming is quickly resolved upon erythroid lineage restriction with both lymphoid and myeloid transcriptional programs rapidly extinguished. However, expression of lymphoid and myeloid factors remains active past nominal lymphoid and myeloid lineage restrictions, revealing a common genetic network utilized by both pathways. Priming and resolution of multilineage potential is dependent on the activity of the DNA binding factor Ikaros. Ikaros primes the lymphoid transcriptional program in the HSC and represses the stem cell and other disparate transcriptional programs downstream of the HSC. Loss of Ikaros removes the lymphoid leg of the immune system and may confer aberrant self-renewing properties to myeloid progenitors. C1 [Yoshida, Toshimi; Ng, Samuel Yao-Ming; Georgopoulos, Katia] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu FU NIH [NIH-R37-AI33062, NIH-R01-AI42254] FX The authors were supported by the NIH grants NIH-R37-AI33062 and NIH-R01-AI42254 to K. Georgopoulos. The authors were supported by the NIH-R37-AI33062 and NIH-R01-AI42254 grants to K. Georgopoulos. NR 35 TC 28 Z9 28 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2010 VL 22 IS 2 BP 154 EP 160 DI 10.1016/j.coi.2010.02.011 PG 7 WC Immunology SC Immunology GA 598CX UT WOS:000277811800003 PM 20299195 ER PT J AU Kreslavsky, T Gleimer, M von Boehmer, H AF Kreslavsky, Taras Gleimer, Michael von Boehmer, Harald TI alpha beta versus gamma delta lineage choice at the first TCR-controlled checkpoint SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL-RECEPTOR; LOOP-HELIX PROTEINS; PRE-TCR; LYMPHOCYTE DEVELOPMENT; THYMOCYTE DEVELOPMENT; BETA/GAMMA-DELTA; IGE PRODUCTION; IMMUNE CELLS; FATE; EXPRESSION AB alpha beta and gamma delta T cells develop in the thymus from a common precursor. Although lineages initially were defined by the type of TCR they express, it soon became clear that the TCR type per se does not play a deterministic role in the lineage decision, since in various transgenic and knockout models, as well as in a small fraction of cells in wt mice, the TCR gamma delta can drive the differentiation of alpha beta lineage cells and the TCR alpha beta can drive differentiation of gamma delta lineage cells. Thus until recently it was unclear what determines lineage choice and at which stage the two lineages diverge. Recent observations suggest that TCR signal strength determines lineage fate and that lineage choice is made at or shortly after the first TCR-controlled checkpoint. While it is clear that the decision between alpha beta and gamma delta lineages is made at the first TCR-controlled checkpoint and the alpha beta sublineages split off later, it is less clear whether gamma delta sublineages divert already at the first TCR-controlled checkpoint or later. Recent experiments support the former view. C1 [Kreslavsky, Taras; Gleimer, Michael; von Boehmer, Harald] Dana Farber Canc Inst, Lab Lymphocyte Biol Canc Immunol & AIDS, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Dana Farber Canc Inst, Lab Lymphocyte Biol Canc Immunol & AIDS, 44 Binney St,Smith 736, Boston, MA 02115 USA. EM Harald_Von_Boehmer@dfci.harvard.edu FU National Institutes of Health [R01 A145846, R01 A151378] FX We thank Anna Malzeva, Gleb Turchinovich and Susan Schlenner for critical reading and helpful discussion of this review. These studies were supported by National Institutes of Health Grants R01 A145846 and R01 A151378. NR 57 TC 13 Z9 13 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2010 VL 22 IS 2 BP 185 EP 192 DI 10.1016/j.coi.2009.12.006 PG 8 WC Immunology SC Immunology GA 598CX UT WOS:000277811800007 PM 20074925 ER PT J AU Herbert, MR AF Herbert, Martha R. TI Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE autism; dynamic encephalopathy; environment; glutathione; oxidative stress; pathophysiology ID INCLUDING DEVELOPMENTAL IMMUNOTOXICITY; BLOOD-BRAIN-BARRIER; DIAGNOSTIC SUBSTITUTION; IMMUNE-RESPONSE; PRENATAL STRESS; ONSET AUTISM; CHILDREN; PREVALENCE; VACCINES; EXPOSURE AB Purpose of review This review presents a rationale and evidence for contributions of environmental influences and environmentally vulnerable physiology to autism spectrum disorders (ASDs). Recent findings Recent studies suggest a substantial increase in ASD prevalence above earlier Centers for Disease Control figures of one in 150, only partly explicable by data artifacts, underscoring the possibility of environmental contributors to increased prevalence. Some gene variants in ASD confer altered vulnerability to environmental stressors and exposures. De-novo mutations and advanced parental age as a risk factor for ASD also suggest a role for environment. Systemic and central nervous system pathophysiology, including oxidative stress, neuroinflammation, and mitochondrial dysfunction can be consistent with a role for environmental influence (e. g. from air pollution, organophosphates, heavy metals) in ASD, and some of the underlying biochemical disturbances (such as abnormalities in glutathione, a critical antioxidant and detoxifier) can be reversed by targeted nutritional interventions. Dietary factors and food contaminants may contribute risk. Improvement and loss of diagnosis in some with ASD suggest brain circuitry amenable to environmental modulation. Summary Prevalence, genetic, exposure, and pathophysiological evidence all suggest a role for environmental factors in the inception and lifelong modulation of ASD. This supports the need for seeking targets for early and ongoing medical prevention and treatment of ASD. C1 Massachusetts Gen Hosp, TRANSCEND Res Program, Charlestown, MA 02129 USA. RP Herbert, MR (reprint author), Massachusetts Gen Hosp, TRANSCEND Res Program, 149 13th St,Room 10-018, Charlestown, MA 02129 USA. EM mherbert1@partners.org FU National Institute of Health (NINDS); Department of Defense Autism Spectrum Disorders Research Program; Nancy Lurie Marks Family Foundation; Autism Society FX The present study was supported by National Institute of Health (NINDS), Department of Defense Autism Spectrum Disorders Research Program, Nancy Lurie Marks Family Foundation, Autism Society. NR 102 TC 128 Z9 133 U1 3 U2 38 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1350-7540 EI 1473-6551 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2010 VL 23 IS 2 BP 103 EP 110 DI 10.1097/WCO.0b013e328336a01f PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577BU UT WOS:000276196700003 PM 20087183 ER PT J AU Newton, AW Vandeven, AM AF Newton, Alice W. Vandeven, Andrea M. TI Child abuse and neglect: a worldwide concern SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE abusive head trauma; child abuse; child maltreatment; child sexual abuse; neglect; shaken baby syndrome ID HEAD TRAUMA; MALTREATMENT; TRIAL; TELEMEDICINE; PREVENTION; BEHAVIORS; KNOWLEDGE; FATHERS; CARE AB Purpose of review As knowledge about child abuse and neglect increases worldwide, so does the literature on abuse and neglect. The authors explore many studies published this year, with attention to the advances in understanding which are guiding prevention efforts as well as diagnosis and treatment of abuse and neglect. Recent findings The evidence base for many forms of child abuse continues to grow. Controversy around the diagnosis of child abuse still continues, with current debate focused on the diagnosis of abusive head injury and whether children with vitamin D deficiency are misdiagnosed with abusive fractures. As clinicians begin to understand the factors which may increase child vulnerability to abuse, more sophisticated and focused prevention efforts are being implemented, and researchers are evaluating these efforts with an eye to whether or not they really contribute to prevention. Summary The short-term and long-term impact of child maltreatment is significant not only for individuals but for families and communities in which abuse is taking place. General pediatricians have an important role to play with families and in the community as advocates for the protection of children. However, it is clear that specialists in child abuse should also play a role in order for diagnosis and management of abuse to adhere to a high standard of care. This has been validated this year by the creation of Child Abuse Pediatrics as a board certified specialty in the United States. As knowledge about abuse and neglect grows, clinicians are focusing on prevention as well as diagnosis and treatment. C1 [Newton, Alice W.] Harvard Univ, Massachusetts Gen Hosp, Child Protect Consultat Program,Dept Pediat, Childrens Hosp,Child Protect Program,Med Sch, Boston, MA 02115 USA. [Vandeven, Andrea M.] Univ Missouri, Childrens Mercy Hosp, Dept Pediat, CARE Program, Kansas City, MO 64108 USA. RP Newton, AW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Child Protect Consultat Program,Dept Pediat, Childrens Hosp,Child Protect Program,Med Sch, 300 Longwood Ave, Boston, MA 02115 USA. EM alice.newton@childrens.harvard.edu NR 41 TC 7 Z9 8 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD APR PY 2010 VL 22 IS 2 BP 226 EP 233 DI 10.1097/MOP.0b013e3283377931 PG 8 WC Pediatrics SC Pediatrics GA 578XQ UT WOS:000276330900017 PM 20164772 ER PT J AU Carinci, AJ Mehta, P Christo, PJ AF Carinci, Adam J. Mehta, Pankaj Christo, Paul J. TI Chronic Pain in Torture Victims SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Torture; Chronic pain; Pain sequelae; Refugee; Posttraumatic stress disorder; Psychological stress; Epidemiology; Rehabilitation; Treatment; Cognitive behavioral therapy ID POSTTRAUMATIC-STRESS-DISORDER; LOW-BACK-PAIN; PSYCHOLOGICAL-ASSESSMENT; MUSCULOSKELETAL PAIN; CLINICAL-TRIAL; MENTAL-HEALTH; CARE PRACTICE; WAR TRAUMA; SURVIVORS; INTERNET AB Torture is widely practiced throughout the world. Recent studies indicate that 50% of all countries, including 79% of the G-20 countries, continue to practice systematic torture despite a universal ban. It is well known that torture has numerous physical, psychological, and pain-related sequelae that can inflict a devastating and enduring burden on its victims. Health care professionals, particularly those who specialize in the treatment of chronic pain, have an obligation to better understand the physical and psychological effects of torture. This review highlights the epidemiology, classification, pain sequelae, and clinical treatment guidelines of torture victims. In addition, the role of pharmacologic and psychologic interventions is explored in the context of rehabilitation. C1 [Carinci, Adam J.; Mehta, Pankaj] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pain Med,Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Christo, Paul J.] Johns Hopkins Univ, Sch Med, Div Pain Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. RP Carinci, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pain Med,Dept Anesthesia Crit Care & Pain Med, 15 Parkman St, Boston, MA 02114 USA. EM acarinci@partners.org; pmehta4@partners.org; pchristo@jhmi.edu NR 72 TC 12 Z9 12 U1 0 U2 4 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1531-3433 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD APR PY 2010 VL 14 IS 2 BP 73 EP 79 DI 10.1007/s11916-010-0101-2 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 574BT UT WOS:000275964100001 PM 20425195 ER PT J AU Shah, A Singh, H Sachdev, V Lee, J Yotsukura, S Salgia, R Bharti, A AF Shah, Ankur Singh, Harpreet Sachdev, Vibhu Lee, James Yotsukura, Sohiya Salgia, Ravi Bharti, Ajit TI Differential Serum Level of Specific Haptoglobin Isoforms in Small Cell Lung Cancer SO CURRENT PROTEOMICS LA English DT Review DE Serum; haptoglobin; Isoforms; small cell lung cancer ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; TUMOR BIOMARKERS; GLYCOPROTEINS; FUCOSYLATION; EVOLUTION; DIAGNOSIS; PROTEINS; DISEASE; MARKERS; GENE AB Lung cancer is the leading cause of cancer death for both men and women in the United States, and similar trends are seen world wide. The lack of early diagnosis is one of the primary reasons for the high mortality rate. A number of biomarkers have been evaluated in lung cancer patients, however, their specificity and early stage diagnostic values are limited. Using traditional protein chemistry and proteomics tool we have demonstrated higher serum haptoglobin levels in small cell lung cancer (SCLC). Similar findings have been reported for other cancers including ovarian cancer and glioblastoma. Haptoglobin is an acute phase protein with at least six possible phenotypes. The six phenotypes, in combination with two post translational modifications, glycosylation and deamidation, lead to large numbers of possible haptoglobin isoforms. Recent studies indicate a possible correlation between specific haptoglobin glycosylation and particular disease conditions. In our current study, we have fractionated control and SCLC patient serum by 2-D gel electrophoresis to identify differentially expressed haptoglobin isoforms in SCLC serum samples. C1 [Shah, Ankur; Singh, Harpreet; Sachdev, Vibhu; Yotsukura, Sohiya; Bharti, Ajit] Boston Univ, Dept Med, Sect Mol Med, Sch Med, Boston, MA 02118 USA. [Lee, James] Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA. [Salgia, Ravi] Univ Chicago, Hematol Oncol Sect, Dept Med, Med Ctr,Canc Ctr,Pritzker Sch Med, Chicago, IL 60637 USA. RP Bharti, A (reprint author), Boston Univ, Dept Med, Sect Mol Med, Sch Med, 88 E Newton St, Boston, MA 02118 USA. EM bharti@bu.edu OI Yotsukura, Sohiya/0000-0003-0233-9043 FU Department of Medicine; National Cancer Institute [5R01CA100750-06] FX We are grateful to Paul Morrison for providing us the resources at Blais Proteomics Center at the Dana-Farber Cancer Institute. This work was supported by a pilot grant from the Department of Medicine to Ajit Bharti and 5R01CA100750-06 from National Cancer Institute to Ravi Salgia. NR 31 TC 14 Z9 14 U1 1 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-1646 J9 CURR PROTEOMICS JI Curr. Proteomics PD APR PY 2010 VL 7 IS 1 BP 49 EP 56 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 573QP UT WOS:000275930000005 PM 20526421 ER PT J AU Brouda, I Edison, B Van Cott, A Green, BA AF Brouda, Irina Edison, Brenda Van Cott, Alicia Green, Barbara A. TI Tolerability and Cosmetic Acceptability of Liquor Carbonis Distillate (Coal Tar) Solution 15% as Topical Therapy for Plaque Psoriasis SO CUTIS LA English DT Article ID CALCIPOTRIOL CREAM AB Although generally recognized as an effective therapy for psoriasis, coal tar therapy lost appeal in modern clinical practice due to poor patient acceptability of its aesthetic properties A new liquor carbonis distillate (LCD) solution 15% (equivalent to coal tar 2.3%) that uses an evaporative and transparent vehicle, fragrance, and a dab-on applicator was developed Cosmetic acceptability of the LCD solution was compared to calcipotriene cream 0.005% during a randomized, active-controlled, investigator-blinded clinical trial Participants with moderate plaque psoriasis applied LCD solution or calcipotriene cream twice daily to body lesions for 12 weeks and then were followed for 6 additional weeks without treatment Participants completed a cosmetic acceptability survey about their medications after starting therapy. Mean ratings for aesthetic and product performance attributes were high in both groups, however, more participants treated with LCD solution versus calcipotriene cream rated their product as more convenient and beneficial compared to prior psoriasis therapies Ratings of the scent, staining, drying time, and dab-on applicator for the LCD solution were favorable Participant experience with LCD solution in this study suggests that it is a cosmetically acceptable psoriasis treatment that is comparable to calcipotriene cream Cutis 2010,85 214-220 C1 [Brouda, Irina; Edison, Brenda; Green, Barbara A.] NeoStrata Co Inc, Princeton, NJ USA. [Van Cott, Alicia] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Green, BA (reprint author), NeoStrata Co Inc, 307 Coll Rd E, Princeton, NJ USA. FU NeoStrata Company, Inc FX This study was supported by a grant from NeoStrata Company, Inc Ms Brouda, Mrs Edison, and Mrs Green are employees of NeoStrata Company, Inc Mrs Van Cott is an employee and investigator for the Clinical Unit for Research Trials in Skin, Department of Dermatology, Massachusetts General Hospital, Boston Correspondence. Barbara A Green. MS, NeoStrata Company, Inc, 307 College Rd E, Princeton, NJ (bgreen@neostrata com) NR 17 TC 3 Z9 4 U1 0 U2 1 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 J9 CUTIS JI Cutis PD APR PY 2010 VL 85 IS 4 BP 214 EP 220 PG 7 WC Dermatology SC Dermatology GA 589XU UT WOS:000277188300011 PM 20486463 ER PT J AU Arbuckle, HA AF Arbuckle, H. Alan TI Epidermolysis Bullosa Care in the United States SO DERMATOLOGIC CLINICS LA English DT Article DE Epidermolysis bullosa; EB centers; Interdisciplinary; Immunomapping AB There is a wide range of health care delivery systems within the United States for patients with epidermolysis bullosa (EB). They range from nonexistent, primarily because of remote geographic locations, to 4 comprehensive interdisciplinary EB centers. This article lists the subspecialties available at each of the 4 centers. C1 [Arbuckle, H. Alan] Denver VA Med Ctr, Dermatol Serv, Dept Dermatol, Denver, CO 80220 USA. [Arbuckle, H. Alan] Childrens Hosp, Epidermolysis Bullosa Clin, Aurora, CO 80045 USA. RP Arbuckle, HA (reprint author), Denver VA Med Ctr, Dermatol Serv, Dept Dermatol, 1055 Clermont St, Denver, CO 80220 USA. EM Alan.Arbuckle@ucdenver.edu NR 1 TC 5 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD APR PY 2010 VL 28 IS 2 BP 387 EP + DI 10.1016/j.det.2010.02.012 PG 4 WC Dermatology SC Dermatology GA 604ME UT WOS:000278282300029 PM 20447508 ER PT J AU Sherling, M Friedman, PM Adrian, R Burns, AJ Conn, H Fitzpatrick, R Gregory, R Kilmer, S Lask, G Narurkar, V Katz, TM Avram, M AF Sherling, Michael Friedman, Paul M. Adrian, Robert Burns, A. Jay Conn, Howard Fitzpatrick, Richard Gregory, Richard Kilmer, Suzanne Lask, Gary Narurkar, Vic Katz, Tracy M. Avram, Mathew TI Consensus Recommendations on the Use of an Erbium-Doped 1,550-nm Fractionated Laser and Its Applications in Dermatologic Laser Surgery SO DERMATOLOGIC SURGERY LA English DT Article ID PHOTOTHERMOLYSIS; ASIANS; SCARS AB BACKGROUND Nonablative fractional photothermolysis has revolutionized the way we treat a number of common skin conditions with laser technology. OBJECTIVE A comprehensive guide is needed for clinicians using this technology to treat specific skin conditions in various skin types. MATERIALS AND METHODS Recommendations were made from a recent round table discussion among experienced physicians and a review of recent literature findings. RESULTS Optimal laser parameters are dependent on patient skin type and condition. We recommended guidelines for the successful treatment of several common skin conditions on and off the face using nonablative fractional photothermolysis. Specific conditions were dyschromia, rhytides, acne scars, surgical scars, melasma, and striae distensae. CONCLUSIONS We developed reproducible guidelines to most effectively treat a variety of skin types and conditions using nonablative fractional photothermolysis. Future large, multicenter trials are indicated for further optimization of treatment parameters. C1 [Sherling, Michael] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Friedman, Paul M.; Katz, Tracy M.] DermSurg Associates, Houston, TX USA. [Friedman, Paul M.] Univ Texas Houston, Houston, TX USA. [Friedman, Paul M.] Methodist Hosp, Houston, TX 77030 USA. [Adrian, Robert] Ctr Laser Surg, Washington, DC USA. [Burns, A. Jay] Dallas Plast Surg Inst, Dallas, TX USA. [Conn, Howard] Howard Conn MD Inc, Irvine, CA USA. [Fitzpatrick, Richard] La Jolla Cosmet Surg Ctr, La Jolla, CA USA. [Gregory, Richard] Inst Aesthet Surg, Celebration, FL USA. [Kilmer, Suzanne] Laser & Skin Surg Ctr No Calif, Sacramento, CA USA. [Lask, Gary] Indianer Lask & Rosenzweig, Encino, CA USA. [Lask, Gary] Univ Calif Los Angeles, David Geffen Sch Med, Encino, CA USA. [Narurkar, Vic] Univ Calif Davis, Sch Med, San Francisco, CA USA. [Narurkar, Vic] Bay Area Laser Inst, San Francisco, CA USA. [Avram, Mathew] Massachusetts Gen Hosp, Laser & Cosmet Ctr, Boston, MA 02114 USA. RP Friedman, PM (reprint author), 7515 Main St,Suite 240, Houston, TX 77030 USA. EM pmfriedman@dermsurgery.org NR 25 TC 60 Z9 63 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD APR PY 2010 VL 36 IS 4 BP 461 EP 469 DI 10.1111/j.1524-4725.2010.01483.x PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA 576SL UT WOS:000276168500004 PM 20187898 ER PT J AU Yoshii, A Constantine-Paton, M AF Yoshii, Akira Constantine-Paton, Martha TI Postsynaptic BDNF-TrkB Signaling in Synapse Maturation, Plasticity, and Disease SO DEVELOPMENTAL NEUROBIOLOGY LA English DT Article DE BDNF; TrkB; PSD-95; LTP; synaptic tag ID LONG-TERM POTENTIATION; NERVE GROWTH-FACTOR; AMPA RECEPTOR TRAFFICKING; NEUROTROPHIC FACTOR BDNF; RAT VISUAL-CORTEX; DENDRITIC SPINE FORMATION; OCULAR DOMINANCE COLUMNS; FAMILY-BASED ASSOCIATION; HIPPOCAMPAL-NEURONS; TUBEROUS-SCLEROSIS AB Brain-derived neurotrophic factor (BDNF) is a prototypic neurotrophin that regulates diverse developmental events from the selection of neural progenitors to the terminal dendritic differentiation and connectivity of neurons. We focus here on activity-dependent synaptic regulation by BDNF and its receptor, full length TrkB. BDNF-TrkB signaling is involved in transcription, translation, and trafficking of proteins during various phases of synaptic development and has been implicated in several forms of synaptic plasticity. These functions are carried out by a combination of the three signaling cascades triggered when BDNF binds TrkB: The mitogen-activated protein kinase (MAPK), the phospholipase C gamma (PLC PLC gamma), and the phosphatidylinositol 3-kinase (PI3K) pathways. MAPK and PI3K play crucial roles in both translation and/or trafficking of proteins induced by synaptic activity, whereas PLC gamma regulates intracellular Ca(2+) that can drive transcription via cyclic AMP and a protein kinase C. Conversely, the abnormal regulation of BDNF is implicated in various developmental and neurodegenerative diseases that perturb neural development and function. We will discuss the current state of understanding BDNF signaling in the context of synaptic development and plasticity with a focus on the postsynaptic cell and close with the evidence that basic mechanisms of BDNF function still need to be understood to effectively treat genetic disruptions of these pathways that cause devastating neurodevelopmental diseases. (C) 2010 Wiley Periodicals. Inc. Develop Neurobiol 70: 304-322, 2010 C1 [Yoshii, Akira; Constantine-Paton, Martha] MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Yoshii, Akira; Constantine-Paton, Martha] MIT, Dept Biol, Cambridge, MA 02139 USA. [Yoshii, Akira; Constantine-Paton, Martha] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Constantine-Paton, M (reprint author), MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, E25-618, Cambridge, MA 02139 USA. EM mcpaton@mit.edu FU DoD [TS080074]; NIH [R01EY006039, R01EY014074] FX Contract grant sponsor: DoD Grant: contract grant number: TS080074. Contract grant sponsor: NIH Grant; contract grant numbers: R01EY006039, R01EY014074. NR 134 TC 208 Z9 225 U1 8 U2 32 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1932-8451 J9 DEV NEUROBIOL JI Dev. Neurobiol. PD APR PY 2010 VL 70 IS 5 SI SI BP 304 EP 322 DI 10.1002/dneu.20765 PG 19 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 582TT UT WOS:000276622700005 PM 20186705 ER PT J AU Robertson, S Ishida-Takahashi, R Tawara, I Hu, J Patterson, CM Jones, JC Kulkarni, RN Myers, MG AF Robertson, Scott Ishida-Takahashi, Ryoko Tawara, Isao Hu, Jiang Patterson, Christa M. Jones, Justin C. Kulkarni, Rohit N. Myers, Martin G., Jr. TI Insufficiency of Janus Kinase 2-Autonomous Leptin Receptor Signals for Most Physiologic Leptin Actions SO DIABETES LA English DT Article ID ENERGY-BALANCE; BODY-WEIGHT; GLUCOSE-HOMEOSTASIS; FEEDBACK INHIBITION; FOOD-INTAKE; LONG FORM; MICE; ACTIVATION; NEURONS; PHOSPHORYLATION AB OBJECTIVE-Leptin acts via its receptor (LepRb) to signal the status of body energy stores. Leptin binding to LepRb initiates signaling by activating the associated Janus kinase 2 (Jak2) tyrosine kinase, which promotes the phosphorylation of tyrosine residues on the intracellular tail of LepRb. Two previously examined LepRb phosphorylation sites mediate several, but not all, aspects of leptin action, leading us to hypothesize that Jak2 signaling might contribute to leptin action independently of LepRb phosphorylation sites. We therefore determined the potential role in leptin action for signals that are activated by Jak2 independently of LepRb phosphorylation (Jak2-autonomous signals). RESEARCH DESIGN AND METHODS-We inserted sequences encoding a truncated LepRb mutant (LepRb(Delta 65c), which activates Jak2 normally, but is devoid of other LepRb intracellular sequences) into the mouse Lepr locus. We examined the leptin-regulated physiology of the resulting Delta/Delta mice relative to LepRb-deficient db/db animals. RESULTS-The Delta/Delta animals were similar to db/db animals in terms of energy homeostasis, neuroendocrine and immune function, and regulation of the hypothalamic arcuate nucleus, but demonstrated modest improvements in glucose homeostasis. CONCLUSIONS-The ability of Jak2-autonomous LepRb signals to modulate glucose homeostasis in Delta/Delta animals suggests a role for these signals in leptin action. Because Jak2-autonomous LepRb signals fail to mediate most leptin action, however, signals from other LepRb intracellular sequences predominate. Diabetes 59:782-790, 2010 C1 [Robertson, Scott; Myers, Martin G., Jr.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Ishida-Takahashi, Ryoko; Tawara, Isao; Patterson, Christa M.; Jones, Justin C.; Myers, Martin G., Jr.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Hu, Jiang; Kulkarni, Rohit N.; Myers, Martin G., Jr.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Hu, Jiang; Kulkarni, Rohit N.; Myers, Martin G., Jr.] Harvard Univ, Sch Med, Boston, MA USA. RP Myers, MG (reprint author), Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. EM mgmyers@umich.edu FU National Institutes of Health (NIH) [DK-57631, DK-67536]; American Diabetes Association; American Heart Association; University of Michigan Cancer and Diabetes Centers [NIH CA-46592, NIH DK-20572] FX This work was supported by National Institutes of Health (NIH) DK-57631 (M.G.M.), NIH DK-67536 (R.N.K.), the American Diabetes Association, and the American Heart Association (M.G.M. and SR.). Core support was provided by The University of Michigan Cancer and Diabetes Centers: NIH CA-46592 and NIH DK-20572. NR 45 TC 14 Z9 15 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2010 VL 59 IS 4 BP 782 EP 790 DI 10.2337/db09-1556 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 582MH UT WOS:000276601200003 PM 20068132 ER PT J AU Luo, NL Liu, J Chung, BH Yang, QL Klein, RL Garvey, WT Fu, YC AF Luo, Nanlan Liu, Jian Chung, B. Hong Yang, Qinglin Klein, Richard L. Garvey, W. Timothy Fu, Yuchang TI Macrophage Adiponectin Expression Improves Insulin Sensitivity and Protects Against Inflammation and Atherosclerosis SO DIABETES LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; PIMA INDIAN POPULATION; ADIPOSE-TISSUE; LIPID-ACCUMULATION; CARDIOVASCULAR-DISEASE; SKELETAL-MUSCLE; RESISTANCE; OBESITY; HYPERINSULINEMIA; INFILTRATION AB OBJECTIVE-Adiponectin is one of several important metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low-circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. To investigate adiponectin-mediated changes in metabolism in vivo, we generated transgenic mice that specifically express the gene coding for human adiponectin in mouse macrophages using the human scavenger receptor A-I gene enhancer/promoter. METHODS AND RESULTS-Using this transgenic mouse model, we found that adiponectin expression was associated with reduced whole-animal body and fat-pad weight and an improved lipid accumulation in macrophages when these transgenic mice were fed with a high-fat diet. Moreover, these macrophage Ad-TG mice exhibit enhanced whole-body glucose tolerance and insulin sensitivity with reduced proinflammatory cytokines, MCP-1 and TNF-a (both in the serum and in the metabolic active macrophage), adipose tissue, and skeletal muscle under the high-fat diet condition. Additional studies demonstrated that these macrophage adiponectin transgenic animals exhibit reduced macrophage foam cell formation in the arterial wall when these transgenic mice were crossed with an LDL receptor deficient mouse model and were fed a high-fat diet. CONCLUSIONS-These results suggest that adiponectin expressed in macrophages can physiologically modulate metabolic activities in vivo by improving metabolism in distal tissues. The use of macrophages as carriers for adiponectin, a molecule with antidiabetes, anti-inflammatory, and antiatherogenic properties, provides a novel and unique strategy for studying the mechanisms of adiponectin-mediated alterations in body metabolism in vivo. Diabetes 59:791-799, 2010 C1 [Luo, Nanlan; Liu, Jian; Chung, B. Hong; Yang, Qinglin; Garvey, W. Timothy; Fu, Yuchang] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Klein, Richard L.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Fu, YC (reprint author), Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. EM yfu@uab.edu RI 王, 强/F-4212-2011 FU UAB Diabetes Research and Training Center, NIH [1P60DK0797626-01, PO1-HL55782, DK-38764]; Medical Research Service of the Department of Veterans Affairs; American Diabetes Association [1-07-RA-49] FX We are grateful to the UAB Diabetes Research and Training Center for providing outstanding core services (supported by NIH 1P60DK0797626-01). This work was supported by grants from the National Institutes of Health (PO1-HL55782 and DK-38764), the Merit Review Program of the Medical Research Service of the Department of Veterans Affairs to (W.T.G. and R.L.K.), and the American Diabetes Association (1-07-RA-49) (to Y.F.). NR 32 TC 57 Z9 62 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2010 VL 59 IS 4 BP 791 EP 799 DI 10.2337/db09-1338 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 582MH UT WOS:000276601200004 PM 20350970 ER PT J AU Georgia, S Hinault, C Kawamori, D Hu, J Meyer, J Kanji, M Bhushan, A Kulkarni, RN AF Georgia, Senta Hinault, Charlotte Kawamori, Dan Hu, Jiang Meyer, John Kanji, Murtaza Bhushan, Anil Kulkarni, Rohit N. TI Cyclin D2 Is Essential for the Compensatory beta-Cell Hyperplastic Response to Insulin Resistance in Rodents SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; IN-VIVO; TRANSCRIPTION FACTOR; TARGETED DISRUPTION; PRIMARY MECHANISM; HUMAN ISLETS; MICE; GROWTH; PROLIFERATION; REPLICATION AB OBJECTIVE-A major determinant of the progression from insulin resistance to the development of overt type 2 diabetes is a failure to mount an appropriate compensatory beta-cell hyperplastic response to maintain normoglycemia. We undertook the present study to directly explore the significance of the cell cycle protein cyclin D2 in the expansion of beta-cell mass in two different models of insulin resistance. RESEARCH DESIGN AND METHODS-We created compound knockouts by crossing mice deficient in cyclin D2 (D2KO) with either the insulin receptor substrate 1 knockout (IRS1KO) mice or the insulin receptor liver-specific knockout mice (LIRKO), neither of which develops overt diabetes on its own because of robust compensatory beta-cell hyperplasia. We phenotyped the double knockouts and used RT-qPCR and immunohistochemistry to examine beta-cell mass. RESULTS-Both compound knockouts, D2KO/LIRKO and D2KO/IRS1KO, exhibited insulin resistance and hyperinsulinemia and an absence of compensatory beta-cell hyperplasia. However, the diabetic D2KO/LIRKO group rapidly succumbed early compared with a relatively normal lifespan in the glucose-intolerant D2KO/IRS1KO mice. CONCLUSIONS-This study provides direct genetic evidence that cyclin D2 is essential for the expansion of beta-cell mass in response to a spectrum of insulin resistance and points to the cell-cycle protein as a potential therapeutic target that can be harnessed for preventing and curing type 2 diabetes. Diabetes 59:987-996, 2010 C1 [Hinault, Charlotte; Kawamori, Dan; Hu, Jiang; Meyer, John; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Georgia, Senta; Kanji, Murtaza; Bhushan, Anil] Univ Calif Los Angeles, David Geffen Sch Med, Larry Hillblom Islet Res Ctr, Los Angeles, CA 90095 USA. [Hinault, Charlotte; Kawamori, Dan; Hu, Jiang; Meyer, John; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM abhushan@mednet.ucla.edu; rohit.kulkarni@joslin.harvard.edu OI hinault, charlotte/0000-0002-3588-039X FU Ruth L. Kirschstein National Research Service Award [GM07185]; Manpei Suzuki Diabetes Foundation, Japan; Juvenile Diabetes Research Foundation (JDRF); National Institutes of Health [RO1 DK67536, DK68721, DK068763]; Joslin DERC [DK36836]; Larry Hillblom Research Foundation FX S.G. was supported by Ruth L. Kirschstein National Research Service Award GM07185. D.K. is the recipient of a research fellowship (Manpei Suzuki Diabetes Foundation, Japan) and a Juvenile Diabetes Research Foundation (JDRF) Postdoctoral Fellowship. This work was supported by grants from the National Institutes of Health (RO1 DK67536 and DK68721 [to R.N.K.] and DK068763 [to A.B.]), by Joslin DERC (Specialized Assay and Microscopy Cores) Grant DK36836, by the JDRF (to A.B.), and by the Larry Hillblom Research Foundation (to A.B.). NR 49 TC 37 Z9 39 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2010 VL 59 IS 4 BP 987 EP 996 DI 10.2337/db09-0838 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 582MH UT WOS:000276601200024 PM 20103709 ER PT J AU Fischl, AFR Herman, WH Sereika, SM Hannan, M Becker, D Mansfield, MJ Freytag, LL Milaszewski, K Botscheller, AN Carron-Prochownik, D AF Fischl, Andrea F. Rodgers Herman, William H. Sereika, Susan M. Hannan, Margaret Becker, Dorothy Mansfield, M. Joan Freytag, Linda L. Milaszewski, Kerry Botscheller, Amanda N. Carron-Prochownik, Denise TI Impact of a Preconception Counseling Program for Teens With Type 1 Diabetes (READY-Girls) on Patient-Provider Interaction, Resource Utilization, and Cost SO DIABETES CARE LA English DT Article ID PREGNANCY; CARE AB OBJECTIVE - To evaluate the impact of a preconception counseling program tailored for teens with type I diabetes on cognitive, psychosocial, and behavioral outcomes and to assess its cost-effectiveness. RESEARCH DESIGN AND METHODS - A total of 88 teens with type 1 diabetes from two sites were randomized into the READY-Girls (Reproductive-health Education and Awareness of Diabetes in Youth for Girls) intervention (IG) (n = 43) or standard care (SC) (n = 45) groups. During three diabetes clinic visits, IG subjects viewed a two-part CD-ROM, read a book, and met with a nurse. Program effectiveness was measured by knowledge, attitudes, intentions, and behaviors regarding diabetes, pregnancy, sexuality, and preconception counseling. Assessments occurred at baseline, before and after viewing program materials, and at 9 months. Economic analyses included an assessment of resource utilization, direct medical costs, and a break-even cost analysis. RESULTS - Age range was 13.2-19.7 years (mean +/- SD 16.7 +/- 1.7 years); 6% (n = 5) were African American, and 24% (n = 21) were sexually active. Compared with baseline and SC subjects, IG subjects demonstrated a significant group-by-time interaction for benefit and knowledge of preconception counseling and reproductive health: increasing immediately after the first visit (P < 0.001) and being sustained for 9 months (P < 0.05 benefits; P < 0.001 knowledge). For IG, subjects, preconception counseling barriers decreased over time (P < 0.001), and intention and initiation of preconception counseling and reproductive health discussions increased (P < 0.001). Costs of adverse reproductive outcomes are high. Direct medical costs of READY-Girls were low. CONCLUSIONS - READY-Girls was beneficial and effects were sustained for at least 9 months. This low-cost self-instructional program can potentially empower young women with type 1 diabetes to make well-informed reproductive health choices, adding little time burden or cost to their diabetes management. C1 [Fischl, Andrea F. Rodgers; Sereika, Susan M.; Hannan, Margaret; Botscheller, Amanda N.; Carron-Prochownik, Denise] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [Herman, William H.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Herman, William H.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Becker, Dorothy; Freytag, Linda L.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Mansfield, M. Joan; Milaszewski, Kerry] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Carron-Prochownik, D (reprint author), Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. EM dcpro@pitt.edu FU American Diabetes Association [7-02-CR-06]; General Clinical Research Center of Children's Hospital of Pittsburgh [M01 RR0084]; Pediatric Clinical and Translational Research Center (NIH/NCRR/CTSA) [UL1 RR024153]; National Institutes of Health/National institute of Nursing Research Center for Research in Chronic Disorders [P30NR03924] FX This study was supported by the American Diabetes Association Clinical Research Award (7-02-CR-06), the General Clinical Research Center of Children's Hospital of Pittsburgh (M01 RR0084), the Pediatric Clinical and Translational Research Center (NIH/NCRR/CTSA UL1 RR024153), and the National Institutes of Health/National institute of Nursing Research Center for Research in Chronic Disorders (P30NR03924). NR 14 TC 28 Z9 28 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2010 VL 33 IS 4 BP 701 EP 705 DI 10.2337/dc09-1821 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 584ZI UT WOS:000276793200002 PM 20067963 ER PT J AU Curtis, JM Horton, ES Bahnson, J Gregg, EW Jakicic, JM Regensteiner, JG Ribisl, PM Soberman, JE Stewart, KJ Espeland, MA AF Curtis, Jeffrey M. Horton, Edward S. Bahnson, Judy Gregg, Edward W. Jakicic, John M. Regensteiner, Judith G. Ribisl, Paul M. Soberman, Judith E. Stewart, Kerry J. Espeland, Mark A. CA Look AHEAD Res Grp TI Prevalence and Predictors of Abnormal Cardiovascular Responses to Exercise Testing Among Individuals With Type 2 Diabetes The Look AHEAD (Action for Health in Diabetes) study SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; BLOOD-PRESSURE; PULSE PRESSURE; RISK-FACTORS; TREADMILL EXERCISE; CLINICAL-TRIAL; MEN; MORTALITY; CAPACITY; PERFORMANCE AB OBJECTIVE - We examined maximal graded exercise test (GXT) results in 5,783 overweight/obese men and women, aged 45-76 years, with type 2 diabetes, who were entering the Look AHEAD (Action for Health in Diabetes) study, to determine the prevalence and correlates of exercise-induced cardiac abnormalities. RESEARCH DESIGN AND METHODS - Participants underwent symptom-limited maximal GXTs. Questionnaires and physical examinations were used to determine demographic, anthropometric, metabolic, and health status predictors of abnormal GXT results, which were defined as an ST segment depression >= 1.0 mm, ventricular arrhythmia, angina pectoris, poor postexercise heart rate recovery (<22 bpm reduction 2 min after exercise), or maximal exercise capacity less than 5.0 METs. Systolic blood pressure response to exercise was examined as a continuous variable, without a threshold to define abnormality. RESULTS - Exercise-induced abnormalities were present in 1,303 (22.5%) participants, of which 693 (12.0%) consisted of impaired exercise capacity. ST segment depression occurred in 440(7-6%), abnormal heart rate recovery in 206(5.0%), angina in 63 (1.1%), and arrhythmia in 41(0.7%). Of potential predictors, only greater age was associated with increased prevalence of all abnormalities. Other predictors were associated with some, but not all, abnormalities. Systolic blood pressure response decreased with greater age, duration of diabetes, and history of cardiovascular disease. CONCLUSIONS - We found a high rate of abnormal GXT results despite careful screening for cardiovascular disease symptoms. In this cohort of overweight and obese individuals with type 2 diabetes, greater age most consistently predicted abnormal GXT. Long-term follow-up of these participants will show whether these abnormalities are clinically significant. C1 [Curtis, Jeffrey M.] NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Bahnson, Judy; Espeland, Mark A.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Gregg, Edward W.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Jakicic, John M.] Univ Pittsburgh, Pittsburgh, PA USA. [Regensteiner, Judith G.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Soberman, Judith E.] Univ Tennessee, Memphis, TN USA. [Stewart, Kerry J.] Johns Hopkins Univ, Baltimore, MD USA. RP Curtis, JM (reprint author), NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. EM jfcurtis@mail.nih.gov FU NCATS NIH HHS [UL1 TR000005] NR 24 TC 13 Z9 13 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2010 VL 33 IS 4 BP 901 EP 907 DI 10.2337/dc09-1787 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 584ZI UT WOS:000276793200042 PM 20056948 ER PT J AU Cruz-Gonzalez, I Chia, S Raffel, OC Sanchez-Ledesma, M Senatore, F Wackers, FJ Nathan, DM Jang, IK AF Cruz-Gonzalez, Ignacio Chia, Stanley Raffel, Owen C. Sanchez-Ledesma, Maria Senatore, Fred Wackers, Frans J. Nathan, David M. Jang, Ik-Kyung TI Hyperglycemia on admission predicts larger infarct size in patients undergoing percutaneous coronary intervention for acute ST-segment elevation myocardial infarction SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Hyperglycemia; Diabetes; Infarct size; SPECT ID DIABETES-MELLITUS; BLOOD-GLUCOSE; STRESS HYPERGLYCEMIA; MORTALITY; ERA; QUANTIFICATION; REPERFUSION; PROGNOSIS; HUMANS; IMPACT AB Aims: To determine if hyperglycemia on admission correlates to infarct size measured by single-photon emission computed tomography (SPECT) in patients with acute ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Methods: We evaluated 347 STEMI patients who underwent primary PCI. Infarct size was determined by SPECT on Day 5. The population was divided into: hyperglycemia (glycemia on admission >11 mmol/L) or non-hyperglycemia (<= 11 mmol/L) regardless of diabetic status. Results: 61 (17.6%) patients presented with hyperglycemia on admission. There were no significant differences in baseline characteristics or in PCI characteristics between the two groups. Final TIMI 3 flow was achieved in 81.7% of patients with hyperglycemia vs 85.7% of patients with non-hyperglycemia (p = 0.43). The infarct size was larger in the hyperglycemia group (6 [2-14]% vs 8.5 [3-18.25]%; p = 0.016). A multivariate linear regression analysis showed that hyperglycemia on admission was an independent predictor of infarct size at Day 5 post-MI (p = 0.004). Conclusion: In patients with STEMI treated with primary PCI, hyperglycemia on admission is associated with larger infarct size determined by SPECT. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Cruz-Gonzalez, Ignacio; Chia, Stanley; Raffel, Owen C.; Sanchez-Ledesma, Maria; Jang, Ik-Kyung] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Senatore, Fred] Mitsubishi Pharma Amer Inc, Warren, NJ USA. [Wackers, Frans J.] Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. [Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org RI IBSAL, Secretaria/H-3719-2011 FU Mitsubishi Pharma Corporation, Osaka, Japan; Spanish Society of Cardiology [2007]; Medtronic Iberia S.A.; Health Manpower Development Program Fellowship; National Medical Research Council Medical Research Fellowship, Singapore FX The study was supported by a grant from Mitsubishi Pharma Corporation, Osaka, Japan. Dr. Jang was the chairman of the EVOLVE study scientific advisory committee and received honoraria.; Dr. Cruz-Gonzalez would like to acknowledge the support of the Spanish Society of Cardiology (Post-fellowship research grant 2007) and Medtronic Iberia S.A.; Dr. Chia is the recipient of the Health Manpower Development Program Fellowship and National Medical Research Council Medical Research Fellowship, Singapore. NR 32 TC 12 Z9 14 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD APR PY 2010 VL 88 IS 1 BP 97 EP 102 DI 10.1016/j.diabres.2010.01.001 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 578UO UT WOS:000276321700015 PM 20083319 ER PT J AU Davis, SN Horton, ES Battelino, T Rubin, RR Schulman, KA Tamborlane, WV AF Davis, Stephen N. Horton, Edward S. Battelino, Tadej Rubin, Richard R. Schulman, Kevin A. Tamborlane, William V. TI STAR 3 Randomized Controlled Trial to Compare Sensor-Augmented Insulin Pump Therapy with Multiple Daily Injections in the Treatment of Type 1 Diabetes: Research Design, Methods, and Baseline Characteristics of Enrolled Subjects SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID QUALITY-OF-LIFE; INFUSION; CHILDREN; HYPOGLYCEMIA; ADOLESCENTS; MANAGEMENT; MELLITUS; SYSTEM AB Background: Sensor-augmented pump therapy (SAPT) integrates real-time continuous glucose monitoring (RT-CGM) with continuous subcutaneous insulin infusion (CSII) and offers an alternative to multiple daily injections (MDI). Previous studies provide evidence that SAPT may improve clinical outcomes among people with type 1 diabetes. Sensor-Augmented Pump Therapy for A1c Reduction (STAR) 3 is a multicenter randomized controlled trial comparing the efficacy of SAPT to that of MDI in subjects with type 1 diabetes. Methods: Subjects were randomized to either continue with MDI or transition to SAPT for 1 year. Subjects in the MDI cohort were allowed to transition to SAPT for 6 months after completion of the study. SAPT subjects who completed the study were also allowed to continue for 6 months. The primary end point was the difference between treatment groups in change in hemoglobin A1c (HbA1c) percentage from baseline to 1 year of treatment. Secondary end points included percentage of subjects with HbA1c <= 7% and without severe hypoglycemia, as well as area under the curve of time spent in normal glycemic ranges. Tertiary end points include percentage of subjects with HbA1c <= 7%, key safety end points, user satisfaction, and responses on standardized assessments. Results: A total of 495 subjects were enrolled, and the baseline characteristics similar between the SAPT and MDI groups. Study completion is anticipated in June 2010. Conclusions: Results of this randomized controlled trial should help establish whether an integrated RT-CGM and CSII system benefits patients with type 1 diabetes more than MDI. C1 [Davis, Stephen N.] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Battelino, Tadej] Univ Childrens Hosp, Ljubljana, Slovenia. [Rubin, Richard R.] Johns Hopkins Univ, Baltimore, MD USA. [Schulman, Kevin A.] Duke Univ, Durham, NC USA. [Tamborlane, William V.] Yale Univ, New Haven, CT USA. RP Davis, SN (reprint author), Vanderbilt Univ, Dept Med, 7465 MRB 4,2213 Garland Ave, Nashville, TN 37232 USA. EM steve.davis@vanderbilt.edu OI Battelino, Tadej/0000-0002-0273-4732 FU Medtronic, Inc FX STAR 3 was sponsored by Medtronic, Inc. Novo Nordisk A/S supplied all insulin aspart used in the study. LifeScan, Inc., Bayer Healthcare LLC, and Becton, Dickinson and Company supplied blood glucose meters used in the study. NR 20 TC 22 Z9 24 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD APR PY 2010 VL 12 IS 4 BP 249 EP 255 DI 10.1089/dia.2009.0145 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 565NV UT WOS:000275301700001 PM 20210562 ER PT J AU Egede, LE Ellis, C AF Egede, Leonard E. Ellis, Charles TI The Effects of Depression on Metabolic Control and Quality of Life in Indigent Patients with Type 2 Diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID GLYCEMIC CONTROL; SOCIOECONOMIC-STATUS; AFRICAN-AMERICAN; HEALTH; CARE; SYMPTOMS; MELLITUS; IMPACT; POPULATION; COSTS AB Background: The objective of this study was to assess differences in metabolic control and health-related quality of life (QOL) among depressed and nondepressed adults in an indigent population with type 2 diabetes. Research Design and Methods: Subjects completed validated surveys to assess depression and QOL. Depression was assessed with the Center for Epidemiological Studies-Depression Scale and defined as a score of >= 16. Metabolic control (hemoglobin A1C, total cholesterol, low-density lipoprotein [LDL] cholesterol, and high-density lipoprotein [HDL] cholesterol) measures were abstracted from medical records. We compared demographic characteristics, metabolic control, and QOL by depression status. Ordinary least squares regression was used to assess differences in QOL scores and metabolic control levels by depression status adjusting for covariates. Results: In the study sample (n = 201), approximately 20% (n = 40) were depressed. In unadjusted analyses, subjects with depression had significantly lower SF-12 physical component summary (PCS) scores (30.4 +/- 7.3 vs. 39.6 +/- 11.8, P < 0.001) and mental component summary (MCS) scores (32.8 +/- 10.5 vs. 48.9 +/- 9.2, P <= 0.001) and significantly higher total cholesterol (209.3 +/- 72.1 vs. 186.6 +/- 50.9, P = 0.024) compared to those without depression. No significant differences were observed by depression status in hemoglobin A1C, LDL cholesterol, and HDL cholesterol. After adjustment for relevant covariates, depressed individuals continued to have lower SF-12 PCS (36.1 vs. 39.0, P <= 0.001) and MCS (41.6 vs. 46.8, P <= 0.001) scores, but the difference in total cholesterol levels was no longer significant. Conclusions: In an indigent sample with type 2 diabetes, depression is significantly associated with decreased physical and mental components of QOL. This finding further reinforces the importance of addressing depression in all populations with type 2 diabetes. C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. [Ellis, Charles] Med Univ S Carolina, Dept Hlth Profess, Charleston, SC 29425 USA. [Egede, Leonard E.; Ellis, Charles] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu FU Agency for Health Care Research and Quality, Rockville, MD [5K08HS11418]; Charleston, SC HSRD [REA 08-261]; Veterans Health Administration Health Services Research and Development program [CDA 07-012-3] FX This study was funded by grant 5K08HS11418 from the Agency for Health Care Research and Quality, Rockville, MD. This work represents work supported by the use of facilities at the Center for Disease Prevention and Health Interventions for Diverse Populations funded by the Charleston, SC HSR&D (REA 08-261). C. E. is supported by a career development award (CDA 07-012-3) from the Veterans Health Administration Health Services Research and Development program. NR 36 TC 14 Z9 14 U1 3 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD APR PY 2010 VL 12 IS 4 BP 257 EP 262 DI 10.1089/dia.2009.0143 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 565NV UT WOS:000275301700002 PM 20210563 ER PT J AU Katra, B Klupa, T Skupien, J Szopa, M Nowak, N Borowiec, M Kozek, E Malecki, MT AF Katra, Barbara Klupa, Tomasz Skupien, Jan Szopa, Magdalena Nowak, Natalia Borowiec, Maciej Kozek, Elzbieta Malecki, Maciej T. TI Dipeptidyl Peptidase-IV Inhibitors Are Efficient Adjunct Therapy in HNF1A Maturity-Onset Diabetes of the Young Patients-Report of Two Cases SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID SULFONYLUREAS; MUTATIONS; INSULIN; GENE AB Background: In HNF1A maturity-onset diabetes of the young (MODY), sulfonylurea (SU) is the first-line treatment. Over time, such therapy fails, and additional treatment is required. Dipeptidyl peptidase IV (DPP-IV) inhibitors are new agents that lower blood glucose by prolonging the activity of circulating incretins. Methods: We applied DPP-IV inhibitors in two HNF1A MODY patients whose earlier therapeutic regimen included SU. Results: Case 1, a 39-year-old woman, a carrier of the ArgR171X HNF1A mutation, with a 7-year history of diabetes was on 160mg of gliclazide and 2,000mg of metformin. Her initial hemoglobin A1c (HbA1c) level was 7.2%, while the mean glucose level on the CGMS (R) (Medtronic, Northridge, CA) record was 162mg/dL. Sitagliptine, in a dose of 100mg/day, was added to the previous treatment. Case 2, a 62-year-old woman, a carrier of the IVS7nt-6G>A mutation, with a 41-year history of diabetes was treated with 240mg/day gliclazide and 6 IU of insulin/day. Her initial HbA1c was 8.8%, and average glycemia reached 172mg/dL. In her case, we started the combined therapy with 50mg of vildagliptine twice daily. Patients were reexamined after 3 months, and HbA1c fell to 6.3% in both subjects. Similarly, significant improvement in glycemic control on CGMS was observed as the average glycemia decreased to 114mg/dL and 134mg/dL in Case 1 and Case 2, respectively. No episodes of hypoglycemia or other side effects were recorded. As intravenous glucose tolerance tests (IVGTTs) were performed before and after DPP-IV implementation, we were able to assess their impact on insulin secretion under fasting conditions. We saw a substantial rise in insulin level increment during IVGTT (by 9.8 and 13.4 mIU/L in Case 1 and Case 2, respectively). Conclusions: DPP-IV inhibitors may be an effective tool of combined therapy in HNF1A MODY, and they seem to improve beta-cell function under fasting conditions. C1 [Katra, Barbara; Klupa, Tomasz; Skupien, Jan; Szopa, Magdalena; Nowak, Natalia; Kozek, Elzbieta; Malecki, Maciej T.] Jagiellonian Univ, Coll Med, Dept Metab Dis, PL-31501 Krakow, Poland. [Katra, Barbara; Klupa, Tomasz; Skupien, Jan; Szopa, Magdalena; Kozek, Elzbieta; Malecki, Maciej T.] Univ Hosp, Krakow, Poland. [Skupien, Jan] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Borowiec, Maciej] Med Univ Lodz, Dept Pediat, Lodz, Poland. RP Malecki, MT (reprint author), Jagiellonian Univ, Coll Med, Dept Metab Dis, 15 Kopernika St, PL-31501 Krakow, Poland. EM malecki_malecki@yahoo.com RI Borowiec, Maciej/S-9220-2016 FU EU Framework 7 CEED3; Jagiellonian University Medical College [K/ZDS/000399]; Polish Diabetes Association FX This research was supported by the EU Framework 7 CEED3 grant and funds from the Jagiellonian University Medical College (grant K/ZDS/000399) and from the Polish Diabetes Association. The authors are grateful to Aleksandra Malecka for her linguistic help in the preparation of this manuscript. NR 12 TC 8 Z9 9 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD APR PY 2010 VL 12 IS 4 BP 313 EP 316 DI 10.1089/dia.2009.0159 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 565NV UT WOS:000275301700010 PM 20210571 ER PT J AU Conway, B Miller, RG Costacou, T Fried, L Kelsey, S Evans, RW Orchard, TJ AF Conway, B. Miller, R. G. Costacou, T. Fried, L. Kelsey, S. Evans, R. W. Orchard, T. J. TI Temporal patterns in overweight and obesity in Type 1 diabetes SO DIABETIC MEDICINE LA English DT Article DE intensive therapy; obesity; Type 1 diabetes ID IMPROVED GLYCEMIC CONTROL; WEIGHT-GAIN; UNITED-STATES; BODY-WEIGHT; BLOOD-PRESSURE; COMPLICATIONS; EPIDEMIOLOGY; ADULTS; ALCOHOL; TRENDS AB P>Aims Time trends in overweight and obesity in the general population have been well documented; however, temporal patterns in Type 1 diabetes (T1DM) have not been thoroughly investigated. We therefore assessed temporal patterns in overweight and obesity and predictors of weight change in 589 individuals from the Pittsburgh Epidemiology of Diabetes Complications Study, a cohort of childhood-onset T1DM. Methods Participants were first seen in 1986-1988, when mean age and diabetes duration were 29 and 20 years, respectively, and biennially thereafter for 18 years. Overweight was defined as 25.0 < body mass index (BMI) < 30.0 kg/m2. Obesity was defined as BMI >= 30.0 kg/m2. Results At baseline, the prevalence of overweight and obesity were 28.6% and 3.4%, respectively. After 18 years' follow-up, the prevalence of overweight increased by 47% while the prevalence of obesity increased sevenfold. Seven per cent were on intensive insulin therapy (>= 3 insulin injections per day or on insulin pump) at baseline; by 2004-2007, this was 82%. Predictors of weight change were a higher baseline HbA(1c), symptomatic autonomic neuropathy (inversely), overt nephropathy (inversely), and going onto intensive insulin therapy during follow-up. Conclusions These data demonstrate dramatic weight gain in T1DM and underscore the complexity of weight change in this disease. C1 [Conway, B.; Miller, R. G.; Costacou, T.; Kelsey, S.; Evans, R. W.; Orchard, T. J.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15217 USA. [Conway, B.] Vanderbilt Univ, Div Epidemiol, Nashville, TN USA. [Fried, L.] VA Pittsburgh Healthcare Syst, Univ Dr Div, Pittsburgh, PA USA. RP Orchard, TJ (reprint author), Univ Pittsburgh, Dept Epidemiol, 3512 5th Ave,2nd Fl, Pittsburgh, PA 15217 USA. EM orchardt@edc.pitt.edu OI orchard, trevor/0000-0001-9552-3215 FU National Institutes of Health [DK34818] FX This work was supported by National Institutes of Health (grant number DK34818). These data were presented in part at the 68th Annual American Diabetes Association Scientific Sessions, June 2008. We would like to think the participants of the Epidemiology of Diabetes Complications study for their continued dedication and cooperation. NR 21 TC 86 Z9 87 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD APR PY 2010 VL 27 IS 4 BP 398 EP 404 DI 10.1111/j.1464-5491.2010.02956.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 580RH UT WOS:000276466600005 PM 20536510 ER PT J AU Larkin, ME Backlund, JY Cleary, P Bayless, M Schaefer, B Canady, J Nathan, DM AF Larkin, M. E. Backlund, J. -Y. Cleary, P. Bayless, M. Schaefer, B. Canady, J. Nathan, D. M. CA DCCT EDIC Res Grp TI Disparity in management of diabetes and coronary heart disease risk factors by sex in DCCT/EDIC SO DIABETIC MEDICINE LA English DT Article DE coronary heart disease risk factors; disparities in health care; glycated haemoglobin; Type 1 diabetes; women's health ID CARDIOVASCULAR-DISEASE; FOLLOW-UP; MELLITUS; MORTALITY; WOMEN; COMPLICATIONS; METAANALYSIS; SURVIVAL; COHORT; IMPACT AB P>Aims Coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with diabetes. Sex disparity in the treatment of modifiable CHD risk factors in patients with Type 2 diabetes has been reported previously; however, there is little comparable information in Type 1 diabetes. Methods We performed a cross-sectional analysis of 1153 subjects with Type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort to compare achievement of metabolic and CHD risk factor goals and use of recommended risk factor interventions between the sexes. Results Women were less likely than men to achieve glycated haemoglobin (HbA(1c)) < 7.0% [adjusted odds ratio (AOR) 0.76, 95% confidence interval (CI) 0.57-0.995] or < 8.0% (AOR 0.74, 95% CI 0.58-0.95). Achievement of target lipid levels was not significantly different between the sexes. As in the non-diabetic population, men had higher blood pressure. Women were significantly less likely than men to report using aspirin (AOR 0.77, 0.60-0.99) and angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) (AOR 0.62, 0.49-0.80) and statins (AOR 0.56, 0.43-0.73), even after adjusting for blood pressure and lipid levels, respectively. Reported use of statins was also lower in women than men in the subset that developed a low-density lipoprotein (LDL) cholesterol level > 3.4 mmol/l (39% vs. 60%, P < 0.05). Conclusions In Type 1 diabetes, women report lower frequency than men in the use of interventions that decrease CHD risk. These findings are consistent with reports in the Type 2 diabetic population, showing that risk-reducing measures are underused in women with diabetes. C1 [Larkin, M. E.; Nathan, D. M.; DCCT EDIC Res Grp] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Backlund, J. -Y.; Cleary, P.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Bayless, M.] Univ Iowa, Iowa City, IA USA. [Schaefer, B.] Northwestern Univ, Chicago, IL 60611 USA. [Canady, J.] Univ New Mexico, Albuquerque, NM 87131 USA. RP Larkin, ME (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St,Suite 340, Boston, MA 02114 USA. EM mlarkin1@partners.org FU Division of Diabetes; National Institute of Diabetes and Digestive and Kidney Diseases; National Eye Institute; National Institute of Neurological Disorders and Stroke; General Clinical Research Centers Program; Clinical and Translation Science Centers Program; National Center for Research Resources FX The DCCT/EDIC project is supported by contracts with the Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Eye Institute, the National Institute of Neurological Disorders and Stroke, the General Clinical Research Centers Program and the Clinical and Translation Science Centers Program, National Center for Research Resources, and by Genentech through a Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. The following were contributors of free or discounted supplies and/or equipment: Lifescan, Roche, Aventis, Eli Lilly, OmniPod, Can-Am, B-D, Animas, Medtronic, Medtronic Minimed, Bayer (single donation in 2008) and Omron. NR 25 TC 12 Z9 13 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 EI 1464-5491 J9 DIABETIC MED JI Diabetic Med. PD APR PY 2010 VL 27 IS 4 BP 451 EP 458 DI 10.1111/j.1464-5491.2010.02972.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 580RH UT WOS:000276466600013 PM 20536518 ER PT J AU Gianani, R Campbell-Thompson, M Sarkar, SA Wasserfall, C Pugliese, A Solis, JM Kent, SC Hering, BJ West, E Steck, A Bonner-Weir, S Atkinson, MA Coppieters, K von Herrath, M Eisenbarth, GS AF Gianani, R. Campbell-Thompson, M. Sarkar, S. A. Wasserfall, C. Pugliese, A. Solis, J. M. Kent, S. C. Hering, B. J. West, E. Steck, A. Bonner-Weir, S. Atkinson, M. A. Coppieters, K. von Herrath, M. Eisenbarth, G. S. TI Dimorphic histopathology of long-standing childhood-onset diabetes SO DIABETOLOGIA LA English DT Article DE Autoimmune diabetes; Childhood diabetes; HLA DR3; HLA DR4; Heterogeneity of diabetes; Islet autoantibodies; Organ donors; Pathology of childhood diabetes; Patterns of beta cell loss; Type 1 diabetes ID BETA-CELL; MELLITUS; EXPRESSION; EXPANSION; SURVIVIN; PANCREAS; ISLETS; AGE AB Childhood diabetes is thought to usually result from autoimmune beta cell destruction (type 1A) with eventual total loss of beta cells. Analysis of C-peptide in children characterised at diabetes onset for autoantibodies shows heterogeneous preservation of insulin secretion in long-standing diabetes. The aim of this study was to characterise the pancreases of childhood-onset diabetes in order to define the pathological basis of this heterogeneity. We evaluated 20 cadaveric organ donor pancreases of childhood-onset long-term patients for disease heterogeneity and obtained corresponding C-peptide measurements. Pancreases from the majority of cadaveric donors contained only insulin-deficient islets (14 of 20). The remaining six patients (30%) had numerous insulin-positive cells within at least some islets, with two different histological patterns. Pattern A (which we would associate with type 1A diabetes) had lobular retention of areas with 'abnormal' beta cells producing the apoptosis inhibitor survivin and HLA class I. In pattern B, 100% of all islets contained normal-appearing but quantitatively reduced beta cells without survivin or HLA class I. Our data demonstrate that C-peptide secretion in long-standing diabetic patients can be explained by two different patterns of beta cell survival, possibly reflecting different subsets of type 1 diabetes. C1 [Gianani, R.; Sarkar, S. A.; Solis, J. M.; West, E.; Steck, A.; Eisenbarth, G. S.] Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80055 USA. [Campbell-Thompson, M.; Wasserfall, C.; Atkinson, M. A.] Univ Florida, Dept Pathol, Gainesville, FL 32611 USA. [Pugliese, A.] Diabet Res Inst, Miami, FL USA. [Kent, S. C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Hering, B. J.] Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN USA. [Bonner-Weir, S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Coppieters, K.; von Herrath, M.] La Jolla Inst Allergol & Immunol, La Jolla, CA USA. RP Gianani, R (reprint author), Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, 1775 Aurora Court, Aurora, CO 80055 USA. EM roberto.gianani@ucdenver.edu RI wasserfall, clive/J-9078-2012; OI wasserfall, clive/0000-0002-3522-8932; Campbell-Thompson, Martha/0000-0001-6878-1235 FU Brehm Coalition; NIH [JDRF 1-2008-1021] FX We gratefully acknowledge the JDRF-sponsored nPOD programme and the Brehm Coalition, which supported this study. Some of the experiments were performed by the Diabetes Endocrinology Research Center histology core (P30DK057516), NIH DK 32083. S. A. Sarkar is supported by NIH DK080193 and JDRF 1-2008-1021. NR 18 TC 75 Z9 75 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2010 VL 53 IS 4 BP 690 EP 698 DI 10.1007/s00125-009-1642-y PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 562WU UT WOS:000275087100013 PM 20062967 ER PT J AU Yachimski, P Lee, RA Tramontano, A Nishioka, NS Hur, C AF Yachimski, Patrick Lee, Rebecca A. Tramontano, Angela Nishioka, Norman S. Hur, Chin TI Secular Trends in Patients Diagnosed with Barrett's Esophagus SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Barrett's esophagus; Esophageal adenocarcinoma; Upper gastrointestinal endoscopy; EGD ID HIGH-GRADE DYSPLASIA; BODY-MASS INDEX; ABDOMINAL OBESITY; RISK-FACTORS; THERAPY; ADENOCARCINOMA; SURVEILLANCE; WOMEN; POPULATION; GUIDELINES AB Background It is not known whether there have been recent changes in demographic or clinical characteristics among patients newly diagnosed with Barrett's esophagus (BE), which could be a result of changes in disease epidemiology or of screening or surveillance effects, and could have clinical implications. Aims The aim of this study was to determine whether there has been a shift in age at diagnosis of BE over the past decade. Secondary aims were to determine whether there has been a shift in patient body mass index (BMI) or BE segment length. Methods An endoscopic database at a tertiary medical center was used to identify all esophagogastroduodenoscopies (EGDs) performed between 1997 and 2007. The cohort was restricted to patients newly diagnosed with BE. Pathology records were reviewed to confirm biopsy findings of intestinal metaplasia (IM). Results BE was diagnosed in 378 subjects between 1997 and 2007. Mean age at diagnosis of BE was 60.7 +/- 14.1 years, with mean BMI of 27.4 +/- 5.2 kg/m(2) and mean BE segment length of 4.7 +/- 3.7 cm. Between 1997 and 2007 there was no significant change in mean age at diagnosis, BMI, BE segment length or in proportion of men versus women newly diagnosed. Conclusions Despite an increase in volume of EGDs performed in an open-access endoscopy unit between 1997 and 2007, there was no appreciable shift in age at diagnosis of BE. BMI and BE segment length among newly diagnosed patients also remained stable over this time period. C1 [Yachimski, Patrick; Lee, Rebecca A.; Nishioka, Norman S.; Hur, Chin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Tramontano, Angela; Hur, Chin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA. RP Yachimski, P (reprint author), Vanderbilt Univ, Med Ctr, Div Gastroenterol Hepatol & Nutr, Nashville, TN 37235 USA. EM patrick.yachimski@vanderbilt.edu OI Hur, Chin/0000-0002-2819-7576 FU NIH [T32 DK007191, K07CA107060] FX Grant support for this research was provided by NIH T32 DK007191 (P. Y.) and NIH K07CA107060 (C. H.). NR 26 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD APR PY 2010 VL 55 IS 4 BP 960 EP 966 DI 10.1007/s10620-009-0985-z PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 576OJ UT WOS:000276153900013 PM 19798573 ER PT J AU Rubinsky, AD Kivlahan, DR Volk, RJ Maynard, C Bradley, KA AF Rubinsky, Anna D. Kivlahan, Daniel R. Volk, Robert J. Maynard, Charles Bradley, Katharine A. TI Estimating risk of alcohol dependence using alcohol screening scores SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol dependence; Alcohol screening; Stratum specific likelihood ratio; Risk stratification; Assessment; Treatment ID DISORDERS IDENTIFICATION TEST; BEHAVIORAL-COUNSELING INTERVENTIONS; INTERVIEW SCHEDULE AUDADIS; PRIMARY-CARE VALIDATION; LIKELIHOOD RATIOS; UNITED-STATES; PROBLEM DRINKING; DRUG MODULES; TEST AUDIT; QUESTION AB Brief alcohol counseling interventions can reduce alcohol consumption and related morbidity among non-dependent risky drinkers, but more intensive alcohol treatment is recommended for persons with alcohol dependence. This study evaluated whether scores on common alcohol screening tests could identify patients likely to have current alcohol dependence so that more appropriate follow-up assessment and/or intervention could be offered. This cross-sectional study used secondary data from 392 male and 927 female adult family medicine outpatients (1993-1994). Likelihood ratios were used to empirically identify and evaluate ranges of scores of the AUDIT, the AUDIT-C, two single-item questions about frequency of binge drinking, and the CAGE questionnaire for detecting DSM-IV past-year alcohol dependence. Based on the prevalence of past-year alcohol dependence in this sample (men: 12.2%; women: 5.8%), zones of the AUDIT and AUDIT-C identified wide variability in the post-screening risk of alcohol dependence in men and women, even among those who screened positive for alcohol misuse. Among men, AUDIT zones 5-10, 11-14 and 15-40 were associated with post-screening probabilities of past-year alcohol dependence ranging from 18 to 87%, and AUDIT-C zones 5-6,7-9 and 10-12 were associated with probabilities ranging from 22 to 75%. Among women, AUDIT zones 3-4, 5-8, 9-12 and 13-40 were associated with post-screening probabilities of past-year alcohol dependence ranging from 6 to 94%, and AUDIT-C zones 3, 4-6, 7-9 and 10-12 were associated with probabilities ranging from 9 to 88%. AUDIT or AUDIT-C scores could be used to estimate the probability of past-year alcohol dependence among patients who screen positive for alcohol misuse and inform clinical decision-making. Published by Elsevier Ireland Ltd. C1 [Rubinsky, Anna D.; Kivlahan, Daniel R.; Maynard, Charles; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, NW HSR&D Ctr Excellence, Seattle, WA 98101 USA. [Rubinsky, Anna D.; Maynard, Charles; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Volk, Robert J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Internal Med Ambulatory Treatment & Emer, Houston, TX 77230 USA. RP Rubinsky, AD (reprint author), VA Puget Sound Hlth Care Syst, NW HSR&D Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Anna.Rubinsky@va.gov OI Maynard, Charles/0000-0002-1644-7814; Volk, Robert/0000-0001-8811-5854 FU Northwest Health Services Research and Development Center of Excellence, VA Puget Sound Health Care System, Seattle, WA; National Institute on Alcohol Abuse and Alcoholism [R21AA14672] FX This material is the result of work supported by resources from the Northwest Health Services Research and Development Center of Excellence, VA Puget Sound Health Care System, Seattle, WA. The research reported in this article was supported by National Institute on Alcohol Abuse and Alcoholism R21AA14672. NR 47 TC 60 Z9 61 U1 3 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2010 VL 108 IS 1-2 BP 29 EP 36 DI 10.1016/j.drugalcdep.2009.11.009 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 579NB UT WOS:000276376600005 PM 20042299 ER PT J AU McCall, AA Swan, EEL Borenstein, JT Sewell, WF Kujawa, SG McKenna, MJ AF McCall, Andrew A. Swan, Erin E. Leary Borenstein, Jeffrey T. Sewell, William F. Kujawa, Sharon G. McKenna, Michael J. TI Drug Delivery for Treatment of Inner Ear Disease: Current State of Knowledge SO EAR AND HEARING LA English DT Article ID SENSORINEURAL HEARING-LOSS; SPIRAL GANGLION-CELLS; BLIND CLINICAL-TRIAL; NEURONS IN-VITRO; MENIERES-DISEASE; STEM-CELLS; INTRATYMPANIC DEXAMETHASONE; GUINEA-PIG; COCHLEAR IMPLANTATION; NEUROTROPHIC FACTOR AB Delivery of medications to the inner ear has been an area of considerable growth in both the research and clinical realms during the past several decades. Systemic delivery of medication destined for treatment of the inner ear is the foundation on which newer delivery techniques have been developed. Because of systemic side effects, investigators and clinicians have begun developing and using techniques to deliver therapeutic agents locally. Alongside the now commonplace use of intratympanic gentamicin for Meniere's disease and the emerging use of intratympanic steroids for sudden sensorineural hearing loss, novel technologies, such as hydrogels and nanoparticles, are being explored. At the horizon of inner ear drug-delivery techniques, intracochlear devices that leverage recent advances in microsystems technology are being developed to apply medications directly into the inner ear. Potential uses for such devices include neurotrophic factor and steroid delivery with cochlear implantation, RNA interference technologies, and stem-cell therapy. The historical, current, and future delivery techniques and uses of drug delivery for treatment of inner ear disease serve as the basis for this review. C1 [McCall, Andrew A.; Sewell, William F.; Kujawa, Sharon G.; McKenna, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Sewell, William F.; Kujawa, Sharon G.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Swan, Erin E. Leary] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Sewell, William F.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Kujawa, Sharon G.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP McKenna, MJ (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM Michael_McKenna@meei.harvard.edu FU National Institutes of Health [5R01DC006848-03] FX This work was supported in part by grant number 5R01DC006848-03 from the National Institutes of Health, National Institute on Deafness, and other Communication Disorders. NR 111 TC 55 Z9 59 U1 2 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD APR PY 2010 VL 31 IS 2 BP 156 EP 165 DI 10.1097/AUD.0b013e3181c351f2 PG 10 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 618PR UT WOS:000279368600002 PM 19952751 ER PT J AU Souza, P Gallun, F AF Souza, Pamela Gallun, Frederick TI Amplification and Consonant Modulation Spectra SO EAR AND HEARING LA English DT Article ID SPEECH-INTELLIGIBILITY; HEARING; COMPRESSION; FREQUENCY; ACOUSTICS; ENVELOPE; NOISE AB Objective: In previous work, a simplified version of the modulation spectrum, the Spectral Correlation Index, was shown to be related to consonant error patterns. It is unknown what effect clinical amplification strategies will have on the modulation spectrum. Accordingly, the goals of this study were to examine the effect of clinical amplification strategies on the consonant modulation spectrum and to determine whether there was a relationship between the modulation spectrum and consonant errors for spectrally robust, amplified speech presented to listeners with hearing loss. Design: Participants were 13 adults ( mean age, 67 yrs) with mild to moderate sensorineural hearing loss. Each listener was fit monaurally in the test ear with a 16- band, four-channel behind the ear hearing aid. One memory of the hearing aid was programmed with compression limiting amplification and one with fast-acting wide-dynamic range compression (WDRC) amplification. Twenty-two consonant-vowel syllables were presented to the listener and recorded at the output of the hearing aid using a probe microphone system. A modulation spectrum was obtained for each amplified and unamplified consonant-vowel. Consonant recognition was also measured for each listener. Results: Results show that ( 1) WDRC increased heterogeneity of the modulation spectrum across consonants and ( 2) for spectrally robust speech processed with either compression limiting or WDRC amplification, two consonants with similar modulation spectra are more likely to be confused with one another than are the two consonants with dissimilar modulation spectra. Conclusion: These data expand and confirm earlier results linking the modulation spectrum to specific consonant errors. C1 [Souza, Pamela] Northwestern Univ, Dept Commun Sci & Disorders, Evanston, IL 60208 USA. [Gallun, Frederick] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR USA. RP Souza, P (reprint author), Northwestern Univ, Dept Commun Sci & Disorders, Frances Searle Bldg,2240 Campus Dr, Evanston, IL 60208 USA. EM p-souza@northwestern.edu OI Gallun, Frederick/0000-0002-4145-2199 FU [R01 DC 006014]; [P30 DC 04661]; [CD2 C4963W] FX This work was supported by grants R01 DC 006014 and P30 DC 04661 (to P.S.), and by grant VA RR&D CD2 C4963W (to F.G.). NR 21 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD APR PY 2010 VL 31 IS 2 BP 268 EP 276 DI 10.1097/AUD.0b013e3181c9fb9c PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 618PR UT WOS:000279368600013 PM 20071993 ER PT J AU Trowbridge, JJ Orkin, SH AF Trowbridge, Jennifer J. Orkin, Stuart H. TI DNA methylation in adult stem cells New insights into self-renewal SO EPIGENETICS LA English DT Article DE DNA methylation; epigenetics; somatic stem cell; hematopoietic stem cell; Dnmt1; self-renewal; differentiation ID HEMATOPOIETIC STEM; METHYLTRANSFERASE GENE; MAMMALIAN-CELLS; TRANSGENIC MICE; DNMT3A; BIOTINYLATION; PURIFICATION; RESTRICTION; NEURONS; COMPLEX AB Methylation of cytosine residues in the context of CpG dinucleotides within mammalian DNA is an epigenetic modification with profound effects on transcriptional regulation. A group of enzymes, the DNA methyltransferases (DNMTs) tightly regulate both the initiation and maintenance of these methyl marks. Loss of critical components of this enzymatic machinery results in growth, viability and differentiation defects in both mice and humans, supporting the notion that this epigenetic modification is essential for proper development. Beyond this, DNA methylation also provides a potent epigenetic mechanism for cellular memory needed to silence repetitive elements and preserve lineage specificity over repeated cell divisions throughout adulthood. Recent work highlighting the specialized roles of DNA methylation and methyltransferases in maintaining adult somatic stem cell function suggests that further dissection of these mechanisms will shed new light on the complex nature of self-renewal. C1 [Trowbridge, Jennifer J.; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Trowbridge, Jennifer J.; Orkin, Stuart H.] Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp Boston,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM orkin@bloodgroup.tch.harvard.edu FU Elsa U. Pardee Foundation; Children's Leukemia Research Association FX We thank J.W. Snow, J.A. Perry and J. Xu for discussions. This work was funded in part by the Elsa U. Pardee Foundation and Children's Leukemia Research Association. J. J. T. is a Leukemia & Lymphoma Society fellow, and S.H.O. is an Investigator of the HHMI. NR 30 TC 3 Z9 3 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD APR 1 PY 2010 VL 5 IS 3 AR 11374 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 577BR UT WOS:000276196400004 ER PT J AU Hopkins, LN Myla, SV Grube, E Eles, G Dave, R Jaff, MR Allocco, DJ AF Hopkins, L. Nelson Myla, Subbarao V. Grube, Eberhard Eles, Gustav Dave, Rajesh Jaff, Michael R. Allocco, Dominic J. TI Carotid artery revascularisation in high-surgical-risk patients with the NexStent and the FilterWire EX/EZ: 3-year results from the CABERNET trial SO EUROINTERVENTION LA English DT Article DE Carotid artery; carotid stenosis; stent; stroke; carotid angioplasty ID RECENT NEUROLOGICAL SYMPTOMS; RANDOMIZED CONTROLLED-TRIAL; STENT PLACEMENT; ISCHEMIC-STROKE; FATAL STROKES; SURGERY-TRIAL; ENDARTERECTOMY; STENOSIS; ANGIOPLASTY; PREVENTION AB Aims: To investigate long-term outcomes achieved in high-surgical-risk patients and other clinically-relevant subgroups after carotid stenting with the NexStent and Filterwire EX/EZ devices. Methods and results: CABERNET, a prospective, multicentre, single-arm trial, enrolled 454 patients with extracranial internal carotid artery stenosis (symptomatic >= 50%, n=110; asymptomatic >= 60%, n=344). Early outcomes at one year have been reported. The 3-year Kaplan-Meier estimated event rates were: 7.2%, all stroke; 2.8%, major stroke; 4.8%, ipsilateral stroke; 17.7%, all death; 7.1%, myocardial infarction; 4.4%, target vessel revascularisation. Asymptomatic patients had significantly fewer major strokes than symptomatic patients (1.9% vs. 5.7%, P=0.03) and patients <80 years had significantly fewer ipsilateral strokes than those >= 80 years (3.2% vs. 10.7%, P=0.002). Stroke outcomes did not differ significantly between patients with anatomical risk factors compared with those with comorbid medical risk factors. Conclusions: Long-term outcomes achieved in high-surgical-risk patients with the NexStent and Filterwire EX/EZ devices are favourable. Outcomes may be better in asymptomatic patients or those younger than 80 years of age. These data will be helpful in estimating short-term risks of carotid stenting and balancing these risks against the long-term benefit of stroke prevention. C1 [Hopkins, L. Nelson] SUNY Buffalo, Buffalo, NY 14209 USA. [Myla, Subbarao V.] Hoag Hosp, Newport Beach, CA USA. [Grube, Eberhard] HELIOS Heart Ctr, Siegburg, Germany. [Eles, Gustav] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Dave, Rajesh] Harrisburg Hosp, PinnacleHlth Heart & Vasc Inst, Cent Penn Cardiovasc Res Inst, Harrisburg, PA USA. [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vasc Ctr, Boston, MA USA. [Allocco, Dominic J.] Boston Sci Corp, Natick, MA USA. RP Hopkins, LN (reprint author), SUNY Buffalo, 3 Gates Circle, Buffalo, NY 14209 USA. EM lnhbuffns@aol.com FU Abbott; Boston Scientific Corporation; Cordis Corporation; ev3; Toshiba; Boston Scientific Corporation, Natick, MA FX Drs. S. V Myla, E. Grube, G. Eles, R. Dave, and M. R. Jaff have no conflicts of interest to declare. Dr. L. N. Hopkins receives research study grants from Abbott, Boston Scientific Corporation, Cordis Corporation, and ev3, research grant from Toshiba, speakers' bureau from Abbott: honoraria from C. R. Bard, Inc., Boston Scientific Corporation, and Cordis Corporation: has an ownership interest in AccessClosure, Inc., Boston Scientific Corporation, Micrus Endovascular, and serves as a consultant to, or is a member of, the advisory boards for Abbott, AccessClosure Inc., C. R. Bard, Inc., Boston Scientific Corporation, Cordis Corporation, Gore, Lumen Biomedical, Toshiba and Micrus Endovascular. Dr D. J. Allocco is an employee of Boston Scientific Corporation.; This study was sponsored by Boston Scientific Corporation, Natick, MA. In compliance with the Uniform Requirements for Manuscripts, established by the International Committee of Medical Journal Editors, the sponsor of this study did not impose any impediment, directly or indirectly, on the publication of the study's results. The authors acknowledge the helpful comments from Ruth Starzyk and Olga Tsukurov from Boston Scientific, and the statistical input from the biostatisticians at Boston Scientific. The authors also acknowledge the independent medical writing assistance provided by Pro Scribe Medical Communications (www.proscribe.com.au), funded by Boston Scientific Corporation. Pro Scribe's services complied with international guidelines for Good Publication Practice. NR 27 TC 10 Z9 10 U1 0 U2 0 PU EUROPA EDITION PI TOULOUSE CEDEX 6 PA 5, RUE SAINT-PANTALEON, BP 61508, TOULOUSE CEDEX 6, 31015, FRANCE SN 1774-024X J9 EUROINTERVENTION JI EuroIntervention PD APR PY 2010 VL 5 IS 8 BP 917 EP 924 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 810OG UT WOS:000294134000008 PM 20542776 ER PT J AU Marcus, FI McKenna, WJ Sherrill, D Basso, C Bauce, B Bluemke, DA Calkins, H Corrado, D Cox, MGPJ Daubert, JP Fontaine, G Gear, K Hauer, R Nava, A Picard, MH Protonotarios, N Saffitz, JE Sanborn, DMY Steinberg, JS Tandri, H Thiene, G Towbin, JA Tsatsopoulou, A Wichter, T Zareba, W AF Marcus, Frank I. McKenna, William J. Sherrill, Duane Basso, Cristina Bauce, Barbara Bluemke, David A. Calkins, Hugh Corrado, Domenico Cox, Moniek G. P. J. Daubert, James P. Fontaine, Guy Gear, Kathleen Hauer, Richard Nava, Andrea Picard, Michael H. Protonotarios, Nikos Saffitz, Jeffrey E. Sanborn, Danita M. Yoerger Steinberg, Jonathan S. Tandri, Harikrishna Thiene, Gaetano Towbin, Jeffrey A. Tsatsopoulou, Adalena Wichter, Thomas Zareba, Wojciech TI Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia SO EUROPEAN HEART JOURNAL LA English DT Article DE Arrhythmias, cardiac; Arrhythmogenic right ventricular cardiomyopathy/dysplasia; Death, sudden, cardiac; Diagnosis; Echocardiography; Electrocardiography; Magnetic resonance imaging ID GENOTYPE-PHENOTYPE ASSESSMENT; TASK-FORCE CRITERIA; MAGNETIC-RESONANCE; NAXOS-DISEASE; WOOLLY HAIR; PALMOPLANTAR KERATODERMA; QUANTITATIVE ASSESSMENT; DILATED CARDIOMYOPATHY; ENDOMYOCARDIAL BIOPSY; WALL-MOTION AB Background In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. Methods and Results Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. Conclusions The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. C1 [Marcus, Frank I.; Sherrill, Duane; Gear, Kathleen] Univ Arizona, Tucson, AZ USA. [McKenna, William J.] Heart Hosp, London, England. [Basso, Cristina; Bauce, Barbara; Corrado, Domenico; Nava, Andrea; Thiene, Gaetano] Univ Padua, Sch Med, Padua, Italy. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Calkins, Hugh; Tandri, Harikrishna] Johns Hopkins Univ Hosp, Baltimore, MD USA. [Cox, Moniek G. P. J.; Hauer, Richard] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Daubert, James P.] Univ Rochester, Strong Mem Hosp, Rochester, NY 14642 USA. [Zareba, Wojciech] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Steinberg, Jonathan S.] St Lukes Roosevelt Hosp, New York, NY USA. [Fontaine, Guy] Hop La Pitie Salpetriere, Paris, France. [Picard, Michael H.; Sanborn, Danita M. Yoerger] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Saffitz, Jeffrey E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Protonotarios, Nikos; Tsatsopoulou, Adalena] Yannis Protonotarios Med Ctr, Hora Naxos, Greece. [Towbin, Jeffrey A.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Wichter, Thomas] Marien Hosp, Osnabruck, Germany. RP Marcus, FI (reprint author), Sarver Heart Ctr, 1501 N Campbell,Rm 5153,Box 245037, Tucson, AZ USA. EM fmarcus@u.arizona.edu RI McKenna, William/C-3243-2008; OI McKenna, William/0000-0001-7994-2460; Picard, Michael/0000-0002-9264-3243; Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung & Blood Institute [R13 HL086825]; Office of Rare Disorders [R13 HL086825]; National Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, MD [U01-HL65594, U01-HL65652, U01-HL65691, K23-HL093350]; European Commission, Brussels, Belgium [QLG1-CT-2000-01091]; International Society for Holter and Noninvasive Electrocardiography; Peter French Memorial Foundation, United Desert Charities; Podolsky Family Foundation FX This project was supported by National Institutes of Health research grant R13 HL086825, funded by the National Heart, Lung & Blood Institute and the Office of Rare Disorders, and was supported in part by research grants U01-HL65594, U01-HL65652, U01-HL65691, and K23-HL093350 from the National Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, MD, and by research grant QLG1-CT-2000-01091 5th Framework Programme from the European Commission, Brussels, Belgium. Additional funding was obtained from the International Society for Holter and Noninvasive Electrocardiography and donations from the Peter French Memorial Foundation, United Desert Charities, the Podolsky Family Foundation, and private donors Mr and Mrs L. Becker, Mr and Mrs H. Danz, Mr K. Dorn, Mr T. Livolsi, Mr and Mrs L. Long, and Mr and Mrs H. Wilmerding. NR 59 TC 327 Z9 347 U1 1 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2010 VL 31 IS 7 BP 806 EP 814 DI 10.1093/eurheartj/ehq025 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 586FZ UT WOS:000276892800012 PM 20172912 ER PT J AU Lubitz, SA Rosen, AB Ellinor, PT Benjamin, EJ AF Lubitz, Steven A. Rosen, Alisa B. Ellinor, Patrick T. Benjamin, Emelia J. TI Stroke risk in AF: do AF patterns matter? SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID PAROXYSMAL ATRIAL-FIBRILLATION; EMBOLIC COMPLICATIONS; HOSPITALIZED-PATIENTS; ANTICOAGULATION; THERAPY; PREVENTION; PREVALENCE; TRIALS; TRENDS; CARE C1 [Rosen, Alisa B.; Benjamin, Emelia J.] Boston Univ, Cardiol Sect, Evans Dept Med, Sch Med, Framingham, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Prevent Med Sect, Boston, MA 02118 USA. RP Benjamin, EJ (reprint author), Boston Univ, Cardiol Sect, Evans Dept Med, Sch Med, Framingham, MA USA. EM emelia@bu.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K24 HL105780, R01 HL104156]; NIDA NIH HHS [R21 DA027021] NR 25 TC 4 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2010 VL 31 IS 8 BP 908 EP 910 DI 10.1093/eurheartj/ehq074 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 591DK UT WOS:000277278900009 PM 20299702 ER PT J AU Noble, VE Liteplo, AS Nelson, BP Thomas, SH AF Noble, Vicki E. Liteplo, Andrew S. Nelson, Bret P. Thomas, Stephen H. TI The impact of analgesia on the diagnostic accuracy of the sonographic Murphy's sign SO EUROPEAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE abdominal pain; analgesia; sonographic Murphy's sign; ultrasound ID EARLY PAIN RELIEF; ACUTE ABDOMINAL-PAIN; RANDOMIZED-TRIAL; MORPHINE AB Objectives Administering analgesia to patients with abdominal pain before diagnostic imaging is now accepted as standard practice. However, analgesia before diagnostic right upper quadrant ultrasound continues to be controversial for fear of masking the sonographic Murphy's sign (SMS). This study sought to evaluate the impact of analgesia on the accuracy of the SMS in predicting cholecystitis. We hypothesized that the impact of analgesia on radiologist-performed ultrasound and emergency physician (EP)-performed ultrasound would be equivalent. Methods Thirty patients presenting to the emergency department with abdominal pain were randomized to receive placebo or meperidine for the first two doses of medication. The patients underwent EP performed right upper quadrant ultrasound before and after the administration of medication, in addition to receiving a radiology department ultrasound postmedication. The presence of SMS was then compared with final hospital or pathological diagnosis. Results Eleven of 30 patients (37%) had a final diagnosis of cholecystitis and only one patient had a change in their SMS postmedication. The EP assessment for postmedication SMS had a sensitivity of 0.82 [confidence interval (CI): 0.48-0.97] and specificity of 0.95 (CI: 0.71-0.99) for cholecystitis. The radiology assessment for postmedication SMS had a sensitivity of 0.17 (CI: 0.01-0.63) and specificity of 1 (CI: 0.74-1) for cholecystitis. Conclusion This pilot study shows that analgesia does not significantly change the assessment of SMS when performed by an EP sonographer. It also suggests that EP-performed ultrasound may be more accurate in assessing this predictive sign of cholecystitis. European Journal of Emergency Medicine 17: 80-83 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Noble, Vicki E.; Liteplo, Andrew S.; Nelson, Bret P.; Thomas, Stephen H.] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. [Noble, Vicki E.; Liteplo, Andrew S.; Nelson, Bret P.; Thomas, Stephen H.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Nelson, Bret P.] Mt Sinai Med Ctr, Dept Emergency Med, New York, NY 10029 USA. RP Noble, VE (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson 3B, Boston, MA 02114 USA. EM vnoble@partners.org NR 10 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0969-9546 J9 EUR J EMERG MED JI Eur. J. Emerg. Med. PD APR PY 2010 VL 17 IS 2 BP 80 EP 83 DI 10.1097/MEJ.0b013e32832e9627 PG 4 WC Emergency Medicine SC Emergency Medicine GA 572HT UT WOS:000275819400004 PM 19584736 ER PT J AU Hoybye, C Ragnarsson, O Jonsson, PJ Koltowska-Haggstrom, M Trainer, P Feldt-Rasmussen, U Biller, BMK AF Hoybye, Charlotte Ragnarsson, Oskar Jonsson, Peter J. Koltowska-Haggstrom, Maria Trainer, Peter Feldt-Rasmussen, Ulla Biller, Beverly M. K. TI Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE DEFICIENCY; QUALITY-OF-LIFE; HYPOPITUITARY PATIENTS; CARDIOVASCULAR RISK; PRACTICE GUIDELINE; QOL-AGHDA; THERAPY; POPULATION; DATABASE; DENSITY AB Objective: Patients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment. Design and methods: Data were obtained from KIMS, the Pfizer International Metabolic Database. A retrospective cross-sectional comparison of background characteristics in unmatched cohorts of patients with CD (n=684, 74% women) and nonfunctioning pituitary adenoma (NFPA; n=2990, 39% women) was conducted. In addition, a longitudinal evaluation of 3 years of GH replacement in a subset of patients with controlled CD (n=322) and NFPA (n=748) matched for age and gender was performed. Results: The cross-sectional study showed a significant delay in GHD diagnosis in the CD group, who had a higher prevalence of hypertension, fractures, and diabetes mellitus. In the longitudinal, matched study, the CD group had a better metabolic profile but a poorer quality of life (QoL) at baseline, which was assessed with the disease-specific questionnaire QoL-assessment of GHD in adults. After 3 years of GH treatment (mean dose at 3 years 0.39 mg/day in CD and 0.37 mg/day in NFPA), total and low-density lipoprotein cholesterol decreased, while glucose and HbAlc increased. Improvement in QoL was observed, which was greater in the CD group (-6 CD group versus -5 NFPA group, P<0.01). Conclusion: In untreated GHD, co-morbidities, including impairment of QoL, were more prevalent in controlled CD. Overall, both the groups responded similarly to GH replacement, suggesting that patients with GHD due to CD benefit from GH to the same extent as those with GHD due to NFPA. C1 [Hoybye, Charlotte] Karolinska Univ Hosp, Dept Endocrinol Metab & Diabetol, SE-17176 Stockholm, Sweden. [Ragnarsson, Oskar] Sahlgrens Univ Hosp, Dept Endocrinol, SE-41345 Gothenburg, Sweden. [Jonsson, Peter J.] Pfizer Endocrine Care, KIMS Med Outcomes, SE-19190 Sollentuna, Sweden. [Koltowska-Haggstrom, Maria] Pfizer Global Pharmaceut, Specialty Business Unit, SE-19190 Sollentuna, Sweden. [Feldt-Rasmussen, Ulla] Rigshosp, Dept Med Endocrinol, DK-2100 Copenhagen, Denmark. [Trainer, Peter] Christie Hosp NHS Trust, Dept Endocrinol, Manchester M20 4BX, Lancs, England. [Biller, Beverly M. K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Hoybye, C (reprint author), Karolinska Univ Hosp, Dept Endocrinol Metab & Diabetol, SE-17176 Stockholm, Sweden. EM charlotte.hoybye@karolinska.se OI Ragnarsson, Oskar/0000-0003-0204-9492; Trainer, Peter/0000-0003-0146-3835 FU Pfizer FX The KIMS database is sponsored by Pfizer. NR 29 TC 11 Z9 11 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD APR PY 2010 VL 162 IS 4 BP 677 EP 684 DI 10.1530/EJE-09-0836 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 587XK UT WOS:000277029400005 PM 20089548 ER PT J AU de Lissovoy, G Fraeman, K Teerlink, JR Mullahy, J Salon, J Sterz, R Durtschi, A Padley, RJ AF de Lissovoy, Greg Fraeman, Kathy Teerlink, John R. Mullahy, John Salon, Jeff Sterz, Raimund Durtschi, Amy Padley, Robert J. TI Hospital costs for treatment of acute heart failure: economic analysis of the REVIVE II study SO EUROPEAN JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Acute heart failure; Inotropes; Levosimendan; Dobutamine; Cost-effectiveness; Pharmacoeconomics; Health care; Hospitalization ID RISK STRATIFICATION; LEVOSIMENDAN; DOBUTAMINE; TRIAL; SURVIVAL; EFFICACY; SAFETY; LIDO AB Acute heart failure (AHF) is the leading cause of hospital admission among older Americans. The Randomized EValuation of Intravenous Levosimendan Efficacy (REVIVE II) trial compared patients randomly assigned to a single infusion of levosimendan (levo) or placebo (SOC), each in addition to local standard treatments for AHF. We report an economic analysis of REVIVE II from the hospital perspective. REVIVE II enrolled patients (N = 600) hospitalized for treatment of acute decompensated heart failure (ADHF) who remained dyspneic at rest despite treatment with intravenous diuretics. Case report forms documented index hospital treatment (drug administration, procedures, days of treatment by care unit), as well as subsequent hospital and emergency department admissions during follow-up ending 90 days from date of randomization. These data were used to impute cost of admission based on an econometric cost function derived from > 100,000 ADHF hospital billing records selected per REVIVE II inclusion criteria. Index admission mean length of stay (LOS) was shorter for the levo group compared with standard of care (SOC) (7.03 vs 8.96 days, P = 0.008) although intensive care unit (ICU)/cardiac care unit (CCU) days were similar (levo 2.88, SOC 3.22, P = 0.63). Excluding cost for levo, predicted mean (median) cost for the index admission was levo US $13,590 (9,458), SOC $19,021 (10,692) with a difference of $5,431 (1,234) favoring levo (P = 0.04). During follow-up through end of study day 90, no significant differences were observed in numbers of hospital admissions (P = 0.67), inpatient days (P = 0.81) or emergency department visits (P = 0.41). Cost-effectiveness was performed with a REVIVE-II sub-set conforming to current labeling, which excluded patients with low baseline blood pressure. Assuming an average price for levo in countries where currently approved, there was better than 50% likelihood that levo was both cost-saving and improved survival. Likelihood that levo would be cost-effective for willingness-to-pay below $50,000 per year of life gained was about 65%. In the REVIVE II trial, patients treated with levo had shorter LOS and lower cost for the initial hospital admission relative to patients treated with SOC. Based on sub-group analysis of patients administered per the current label, levo appears cost-effective relative to SOC. C1 [de Lissovoy, Greg; Fraeman, Kathy] United BioSource Corp, Bethesda, MD 20814 USA. [Teerlink, John R.] Univ Calif San Francisco, Cardiol Sect, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Mullahy, John] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. [Salon, Jeff; Sterz, Raimund; Durtschi, Amy; Padley, Robert J.] Abbott Labs, Abbott Pk, IL 60064 USA. RP de Lissovoy, G (reprint author), United BioSource Corp, 7101 Wisconsin Ave,Suite 600, Bethesda, MD 20814 USA. EM greg.delissovoy@unitedbiosource.com RI Teerlink, John/D-2986-2012 NR 17 TC 19 Z9 20 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1618-7598 J9 EUR J HEALTH ECON JI Eur. J. Health Econ. PD APR PY 2010 VL 11 IS 2 BP 185 EP 193 DI 10.1007/s10198-009-0165-2 PG 9 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 567NI UT WOS:000275453400008 PM 19582491 ER PT J AU Lubitz, SA Leong-Sit, P Fine, N Kramer, DB Singh, J Ellinor, PT AF Lubitz, Steven A. Leong-Sit, Peter Fine, Nowell Kramer, Daniel B. Singh, Jagmeet Ellinor, Patrick T. TI Effectiveness of cardiac resynchronization therapy in mild congestive heart failure: systematic review and meta-analysis of randomized trials SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Artificial cardiac pacemaker; Artificial pacemaker; Heart failure; Mortality; Cardiac resynchronization therapy ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; VENTRICULAR SYSTOLIC DYSFUNCTION; INTRAVENTRICULAR-CONDUCTION DELAY; DISEASE PROGRESSION; CLINICAL-TRIALS; TASK-FORCE; PREVENTION; ASSOCIATION; CARDIOMYOPATHY; COLLABORATION AB Aims Cardiac resynchronization therapy (CRT) improves echocardiographic parameters, symptoms, hospitalizations, and mortality in patients with New York Heart Association (NYHA) Class III or IV symptoms with left ventricular systolic dysfunction, sinus rhythm, and a prolonged QRS duration. The effectiveness of CRT in patients with mild heart failure symptoms has not been systematically reviewed. Methods and results Randomized controlled trials of CRT in patients with NYHA Class I or II heart failure were identified from MEDLINE and EMBASE. The effects of CRT on left ventricular remodelling at 1 year were systematically reviewed, and the effects of CRT on clinical outcomes at 1 year were meta-analysed. Two studies met the pre-specified search criteria, with a total of 2430 patients (REVERSE n = 610 and MADIT-CRT n = 1820). CRT was associated with a reduction in heart failure events in both trials [combined OR 0.57, 95% confidence interval (CI) 0.46-0.70], but not mortality (combined OR 0.96, 95% CI 0.67-1.36). The effect of CRT on the combined endpoint of heart failure events or death favoured CRT (OR 0.63, 95% CI 0.51-0.77). CRT was also associated with improvement in left ventricular remodelling parameters in both studies, including a greater increase in left ventricular ejection fraction in the CRT group than in the control group, at 1 year after randomization. Serious adverse events were rare with CRT. Conclusion CRT reduces heart failure events in patients with mild heart failure symptoms, left ventricular dysfunction, sinus rhythm, and prolonged QRS duration. C1 [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Leong-Sit, Peter; Fine, Nowell] London Hlth Sci Ctr, Div Cardiol, London, ON, Canada. [Kramer, Daniel B.] Beth Israel Deaconess Med Ctr, CardioVasc Inst, Boston, MA 02215 USA. [Kramer, Daniel B.] Harvard Univ, Sch Med, Boston, MA USA. [Singh, Jagmeet; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM pellinor@partners.org FU NIH [T32HL007575, HL092577, DA027021] FX S. A. L. is supported by an NIH training grant in the Epidemiology of Cardiovascular Disease (T32HL007575). P. T. E. is supported by grants from the NIH (HL092577 and DA027021). NR 30 TC 18 Z9 23 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD APR PY 2010 VL 12 IS 4 BP 360 EP 366 DI 10.1093/eurjhf/hfq029 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575EI UT WOS:000276049100011 PM 20335354 ER PT J AU Sobrin, L Maller, JB Neale, BM Reynolds, RC Fagerness, JA Daly, MJ Seddon, JM AF Sobrin, Lucia Maller, Julian B. Neale, Benjamin M. Reynolds, Robyn C. Fagerness, Jesen A. Daly, Mark J. Seddon, Johanna M. TI Genetic profile for five common variants associated with age-related macular degeneration in densely affected families: a novel analytic approach SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE AMD; complex trait; simulation; SNPs; liability threshold model ID COMPLEMENT FACTOR-H; RISK; POLYMORPHISM AB About 40% of the genetic variance of age-related macular degeneration (AMD) can be explained by a common variation at five common single-nucleotide polymorphisms (SNPs). We evaluated the degree to which these known variants explain the clustering of AMD in a group of densely affected families. We sought to determine whether the actual number of risk alleles at the five variants in densely affected families matched the expected number. Using data from 322 families with AMD, we used a simulation strategy to generate comparison groups of families and determined whether their genetic profile at the known AMD risk loci differed from the observed genetic profile, given the density of disease observed. Overall, the genotypic loads for the five SNPs in the families did not deviate significantly from the genotypic loads predicted by the simulation. However, for a subset of densely affected families, the mean genotypic load in the families was significantly lower than the expected load determined from the simulation. Given that these densely affected families may harbor rare, more penetrant variants for AMD, linkage analyses and resequencing targeting these families may be an effective approach to finding additional implicated genes. European Journal of Human Genetics (2010) 18, 496-501; doi:10.1038/ejhg.2009.185; published online 21 October 2009 C1 [Sobrin, Lucia] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Sobrin, Lucia; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. [Sobrin, Lucia; Maller, Julian B.; Neale, Benjamin M.; Fagerness, Jesen A.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Maller, Julian B.; Neale, Benjamin M.; Fagerness, Jesen A.; Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Maller, Julian B.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Neale, Benjamin M.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. [Reynolds, Robyn C.; Seddon, Johanna M.] Ophthalm Epidemiol & Genet Serv, Tufts Med Ctr, New England Eye Ctr, Boston, MA 02111 USA. RP Seddon, JM (reprint author), Ophthalm Epidemiol & Genet Serv, Tufts Med Ctr, New England Eye Ctr, 800 Washington St 450, Boston, MA 02111 USA. EM jseddon@tuftsmedicalcenter.org OI Maller, Julian/0000-0002-1565-9559 FU National Eye Institute [EY16335-02]; US National Institutes of Health [EY11309]; Foundation Fighting Blindness; Massachusetts Lions Research Fund, Inc; Ophthalmic Epidemiology and Genetics Service, Tufts Medical Center; Broad Institute Center for Genotyping and Analysis; NCRR [U54 RR020278]; Prevent Blindness Career Development Award; Research to Prevent Blindness FX This research was supported by EY16335-02 (National Eye Institute K12 Harvard Vision Clinician Scientist Development Award); EY11309 from the US National Institutes of Health (National Eye Institute RO1 Grant, JMS); the Foundation Fighting Blindness; Massachusetts Lions Research Fund, Inc; the Macular Degeneration Research Fund, Ophthalmic Epidemiology and Genetics Service, Tufts Medical Center; and by the Broad Institute Center for Genotyping and Analysis, supported by Grant U54 RR020278 from the NCRR. LS is a recipient of a Research to Prevent Blindness Career Development Award and JMS was a recipient of the Research to Prevent Blindness Lew R Wasserman Award. NR 16 TC 19 Z9 19 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD APR PY 2010 VL 18 IS 4 BP 496 EP 501 DI 10.1038/ejhg.2009.185 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 571CF UT WOS:000275726900020 PM 19844262 ER PT J AU Lee, H Brecha, NC AF Lee, Helen Brecha, Nicholas C. TI Immunocytochemical evidence for SNARE protein-dependent transmitter release from guinea pig horizontal cells SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE mammalian visual system; retina; synaptic proteins; synaptic vesicle ID GAMMA-AMINOBUTYRIC-ACID; TIGER SALAMANDER RETINA; VESICULAR GABA TRANSPORTER; SYNAPTIC VESICLE PROTEINS; C-LIKE IMMUNOREACTIVITY; OUTER PLEXIFORM LAYER; IN-SITU HYBRIDIZATION; MULLER GLIAL-CELLS; ROD BIPOLAR CELLS; MOUSE RETINA AB Horizontal cells are lateral interneurons that participate in visual processing in the outer retina but the cellular mechanisms underlying transmitter release from these cells are not fully understood. In non-mammalian horizontal cells, GABA release has been shown to occur by a non-vesicular mechanism. However, recent evidence in mammalian horizontal cells favors a vesicular mechanism as they lack plasmalemmal GABA transporters and some soluble NSF attachment protein receptor (SNARE) core proteins have been identified in rodent horizontal cells. Moreover, immunoreactivity for GABA and the molecular machinery to synthesize GABA have been found in guinea pig horizontal cells, suggesting that if components of the SNARE complex are expressed they could contribute to the vesicular release of GABA. In this study we investigated whether these vesicular and synaptic proteins are expressed by guinea pig horizontal cells using immunohistochemistry with well-characterized antibodies to evaluate their cellular distribution. Components of synaptic vesicles including vesicular GABA transporter, synapsin I and synaptic vesicle protein 2A were localized to horizontal cell processes and endings, along with the SNARE core complex proteins, syntaxin-1a, syntaxin-4 and synaptosomal-associated protein 25 (SNAP-25). Complexin I/II, a cytosolic protein that stabilizes the activated SNARE fusion core, strongly immunostained horizontal cell soma and processes. In addition, the vesicular Ca2+-sensor, synaptotagmin-2, which is essential for Ca2+-mediated vesicular release, was also localized to horizontal cell processes and somata. These morphological findings from guinea pig horizontal cells suggest that mammalian horizontal cells have the capacity to utilize a regulated Ca2+-dependent vesicular pathway to release neurotransmitter, and that this mechanism may be shared among many mammalian species. C1 [Lee, Helen; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Lee, Helen; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Lee, H (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM hlee@jsei.ucla.edu FU NIH [EY 15573]; Jules Stein Eye Institute EyeSTAR program FX We thank Drs Salvatore Stella Jr, Arlene Hirano, Chenying Guo, Iona Raymond and Steve Barnes for their insightful comments on this manuscript. Supported by NIH EY 15573 and the Jules Stein Eye Institute EyeSTAR program. N.C.B. is a VA Senior Career Research Scientist. NR 182 TC 17 Z9 17 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 2010 VL 31 IS 8 BP 1388 EP 1401 DI 10.1111/j.1460-9568.2010.07181.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 585WD UT WOS:000276860000007 PM 20384779 ER PT J AU Bamberg, F Abbara, S Schlett, CL Cury, RC Truong, QA Rogers, IS Nagurney, JT Brady, TJ Hoffmann, U AF Bamberg, Fabian Abbara, Suhny Schlett, Christopher L. Cury, Ricardo C. Truong, Quynh A. Rogers, Ian S. Nagurney, John T. Brady, Thomas J. Hoffmann, Udo TI Predictors of image quality of coronary computed tomography in the acute care setting of patients with chest pain SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Cardiac computed tomography; Coronary CT angiography; Coronary artery disease; Acute chest pain; Image quality ID HEART-RATE-VARIABILITY; DIAGNOSTIC-ACCURACY; ARTERY-DISEASE; 64-SECTION CT; ANGIOGRAPHY; RECONSTRUCTION; RESTENOSIS; PLAQUE; RISK AB Objective: We aimed to determine predictors of image quality in consecutive patients who underwent coronary computed tomography (CT) for the evaluation of acute chest pain. Method and materials: We prospectively enrolled patients who presented with chest pain to the emergency department. All subjects underwent contrast-enhanced 64-slice coronary multi-detector CT. Two experienced readers determined overall image quality on a per-patient basis and the prevalence and characteristics of non-evaluable coronary segments on a per-segment basis. Results: Among 378 subjects (143 women, age: 52.9 +/- 11.8 years), 345 (91%) had acceptable overall image quality, while 33 (9%) had poor image quality or were unreadable. In adjusted analysis, patients with diabetes, hypertension and a higher heart rate during the scan were more likely to have exams graded as poor or unreadable (odds ratio [OR]: 2.94, p = 0.02; OR: 2.62, p = 0.03; OR: 1.43, p = 0.02; respectively). Of 6253 coronary segments, 257 (4%) were non-evaluable, most due to severe calcification in combination with motion (35%). The presence of non-evaluable coronary segments was associated with age (OR: 1.08 annually, 95%-confidence interval [CI]: 1.05-1.12, p < 0.001), baseline heart rate (OR: 1.35 per 10 beats/min, 95%-CI: 1.11-1.67, p = 0.003), diabetes, hypertension, and history of coronary artery disease (OR: 4.43, 95%-CI: 1.93-10.17, p < 0.001; OR: 2.27, 95-CI: 1.01-4.73, p = 0.03; OR: 5.12, 95%-CI: 2.0-13.06, p < 0.001; respectively). Conclusion: Coronary CT permits acceptable image quality in more than 90% of patients with chest pain. Patients with multiple risk factors are more likely to have impaired image quality or non-evaluable coronary segments. These patients may require careful patient preparation and optimization of CT scanning protocols. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Bamberg, Fabian; Abbara, Suhny; Schlett, Christopher L.; Cury, Ricardo C.; Truong, Quynh A.; Rogers, Ian S.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA. [Bamberg, Fabian; Abbara, Suhny; Schlett, Christopher L.; Cury, Ricardo C.; Truong, Quynh A.; Rogers, Ian S.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Bamberg, Fabian; Abbara, Suhny; Schlett, Christopher L.; Cury, Ricardo C.; Truong, Quynh A.; Rogers, Ian S.; Nagurney, John T.; Brady, Thomas J.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, 165 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org FU National Institutes of Health, Bethesda, Maryland [R01 HL080053]; General Electric Healthcare, Waukesha, Wisconsin; Siemens Medical Solutions, Forchheim, Germany FX The study was supported by Grant No. R01 HL080053 from the National Institutes of Health, Bethesda, Maryland; General Electric Healthcare, Waukesha, Wisconsin; and Siemens Medical Solutions, Forchheim, Germany. NR 24 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD APR PY 2010 VL 74 IS 1 SI SI BP 182 EP 188 DI 10.1016/j.ejrad.2009.03.001 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 594UT UT WOS:000277565200029 PM 19346094 ER PT J AU Liu, CH Arellano, RS Uppot, RN Samir, AE Gervais, DA Mueller, PR AF Liu, Chang-Hsien Arellano, Ronald S. Uppot, Raul N. Samir, Anthony E. Gervais, Debra A. Mueller, Peter R. TI Radiofrequency ablation of hepatic tumours: effect of post-ablation margin on local tumour progression SO EUROPEAN RADIOLOGY LA English DT Article DE Radiofrequency ablation; Post-ablation margin; Local tumour progression; Hepatocellular carcinoma; Colorectal liver metastasis ID SMALL HEPATOCELLULAR-CARCINOMA; COLORECTAL LIVER METASTASES; SINGLE SESSION; RISK-FACTORS; RESECTION; ELECTRODES; RECURRENCE; FEATURES; OUTCOMES; LESIONS AB The purpose of this study was to retrospectively evaluate the relationship between post-ablation margins and local tumour progression following radiofrequency ablation (RFA) of hepatocellular carcinomas and colorectal liver metastases. Eighty-three patients with 107 hepatic tumours who underwent RFA were divided into two groups: the hepatocellular carcinoma (HCC) group (55 patients with 69 lesions) and the colorectal liver metastases group (28 patients with 38 lesions). Post-ablation margins were calculated on 1-month follow-up contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) studies. Efficacy was evaluated at 1-month post-ablation, then at 3-month intervals for the first year and biannually thereafter. The results of the log-rank test showed that the minimum threshold post-ablation margin of 0.4 cm (P = 0.020) and tumour size smaller than 2.5 cm (P = 0.001) significantly correlated with local control for the HCC group. In the colorectal liver metastases group, the results of the log-rank test showed that the minimum threshold post-ablation margin of 0.4 cm (P = 0.345) and tumour size smaller than 2.5 cm (P = 0.168) did not correlate with local control. Percutaneous RFA is more effective in achieving local control in patients with HCCs than with colorectal liver metastases. C1 [Arellano, Ronald S.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Liu, Chang-Hsien; Arellano, Ronald S.; Uppot, Raul N.; Samir, Anthony E.; Gervais, Debra A.; Mueller, Peter R.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Liu, Chang-Hsien] Triserv Gen Hosp, Dept Radiol, Taipei, Taiwan. [Liu, Chang-Hsien] Natl Def Med Ctr, Taipei, Taiwan. RP Arellano, RS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM RARELLANO@PARTNERS.ORG OI Samir, Anthony/0000-0002-7801-8724 NR 24 TC 41 Z9 43 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD APR PY 2010 VL 20 IS 4 BP 877 EP 885 DI 10.1007/s00330-009-1610-4 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 567CZ UT WOS:000275421200014 PM 19760232 ER PT J AU Ohye, H Sugawara, M AF Ohye, Hidemi Sugawara, Masahiro TI Dual oxidase, hydrogen peroxide and thyroid diseases SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review DE dual oxidase; hydrogen peroxide; congenital hypothyroidism; Hashimoto's thyroiditis; papillary thyroid cancer ID AIRWAY EPITHELIAL-CELLS; CONGENITAL HYPOTHYROIDISM; NADPH-OXIDASE; H2O2 GENERATION; GENE-EXPRESSION; IODIDE ORGANIFICATION; FUNCTIONAL-CHARACTERIZATION; H2O2-GENERATING ACTIVITY; MATURATION FACTOR; THOX2 GENE AB The thyroid gland is a unique endocrine organ that requires hydrogen peroxide (H2O2) for thyroid hormone formation. The molecule for H2O2 production in the thyroid gland has been known as dual oxidase 2 (DUOX2). Recently, NADPH oxidase 4 (NOX4), a homolog of the NOX family, was added as a new intracellular source of reactive oxygen species (ROS) in the human thyroid gland. This review focuses on the recent progress of the DUOX system and its possible contribution to human thyroid diseases. Also, we discuss human thyroid diseases related to abnormal H2O2 generation. The DUOX molecule contains peroxidase-like and NADPH oxidase-like domains. Human thyroid gland also contains DUOX1 that shares 83% similarity with the DUOX2 gene. However, thyroid DUOX1 protein appears to play a minor role in H2O2 production. DUOX proteins require DUOX maturation or activation factors (DUOXA1 or 2) for proper translocation of DUOX from the endoplasmic reticulum to the apical plasma membrane, where H2O2 production takes place. Thyroid cells contain antioxidants to protect cells from the H2O2-mediated oxidative damage. Loss of this balance may result in thyroid cell dysfunction and thyroid diseases. Mutation of either DUOX2 or DUOXA2 gene is a newly recognized cause of hypothyroidism due to insufficient H2O2 production. Papillary thyroid carcinoma, the most common thyroid cancer, is closely linked to the increased ROS production by NOX4. Hashimoto's thyroiditis, a common autoimmune thyroid disease in women, becomes conspicuous when iodide intake increases. This phenomenon may be explained by the abnormality of iodide-induced H2O2 or other ROS in susceptible individuals. Discovery of DUOX proteins and NOX4 provides us with valuable tools for a better understanding of pathophysiology of prevalent thyroid diseases. C1 [Ohye, Hidemi; Sugawara, Masahiro] Greater Los Angeles Vet Affair Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA USA. [Ohye, Hidemi; Sugawara, Masahiro] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Sugawara, M (reprint author), Greater Los Angeles VA Hlth Care Syst 111M, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM msugawar@ucla.edu FU VA Merit Review FX We thank Dr Jerome M Hershman for critical reading of the manuscript. This work is supported by the VA Merit Review Research Grant. NR 74 TC 39 Z9 41 U1 1 U2 8 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1535-3702 EI 1535-3699 J9 EXP BIOL MED JI Exp. Biol. Med. PD APR PY 2010 VL 235 IS 4 BP 424 EP 433 DI 10.1258/ebm.2009.009241 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 596NK UT WOS:000277691700003 PM 20407074 ER PT J AU Saito, TI Fujisaki, J Carlson, AL Lin, CP Sykes, M AF Saito, Toshiki I. Fujisaki, Joji Carlson, Alicia L. Lin, Charles P. Sykes, Megan TI Persistence of donor-derived protein in host myeloid cells after induced rejection of engrafted allogeneic bone marrow cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID RECIPIENT LEUKOCYTE INFUSIONS; STEM-CELLS; IFN-GAMMA; RESPONSES; TRANSPLANTATION; MICROVESICLES; CHIMERISM; RECEPTORS; NICHES; MOUSE AB Objective. In recipients of allogeneic hematopoietic stem cell transplantation to treat hematologic malignancies, we have unexpectedly observed anti-tumor effects in association with donor cell rejection in both mice and humans. Host-type CD8 T cells were shown to be required for these anti-tumor effects in the murine model. Because sustained host CD8 T-cell activation was observed in the murine bone marrow following the disappearance of donor chimerism in the peripheral blood, we hypothesized that donor antigen presentation in the bone marrow might be prolonged. Materials and Methods. To assess this hypothesis, we established mixed chimerism with green fluorescent protein (GFP) positive allogeneic bone marrow cells, induced rejection of the donor cells by giving recipient leukocyte infusions, and utilized in vivo microscopy to follow GIP-positive cells. Results. After peripheral donor leukocytes disappeared, GFP persisted within host myeloid cells surrounding the blood vessels in the bone marrow, suggesting that the host myeloid cells captured donor-derived GFP protein. Conclusions. Because the host-vs-graft reaction promotes induction of anti-tumor responses in this model, this retention of donor-derived protein may play a role in the efficacy of recipient leukocyte infusions as an anti-tumor therapy. (C) 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Saito, Toshiki I.; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. [Fujisaki, Joji; Carlson, Alicia L.; Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Adv Microscopy Program, Boston, MA 02114 USA. [Fujisaki, Joji; Carlson, Alicia L.; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Fujisaki, Joji; Lin, Charles P.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH East,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM Megan.Sykes@tbrc.mgh.harvard.edu FU National Institutes of Health [RO1 CA079989-07, P01 CA111519] FX We thank Dr. YongGuang Yang for helpful review of the manuscript, Ms. Ellen Beauchamp and Ms. Nithyaa Venkataramani for technical assistance, and Ms. Germ Coleman for assistance with the manuscript. This work was supported by National Institutes of Health (Bethesda, MD, USA) grants RO1 CA079989-07 and P01 CA111519. NR 18 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 2010 VL 38 IS 4 BP 333 EP 339 DI 10.1016/j.exphem.2010.02.003 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 575GF UT WOS:000276054300008 PM 20167247 ER PT J AU Sethi, S AF Sethi, Sanjay TI Antibiotics in acute exacerbations of chronic bronchitis SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Review DE antimicrobial resistance; chronic bronchitis; COPD; exacerbation; Haemophilus influenzae; Moraxella catarrhalis; Streptococcus pneumoniae ID OBSTRUCTIVE PULMONARY-DISEASE; RESISTANT STREPTOCOCCUS-PNEUMONIAE; RESPIRATORY-TRACT INFECTIONS; TRUST SURVEILLANCE PROGRAM; LONG-TERM OUTCOMES; HAEMOPHILUS-INFLUENZAE; ANTIMICROBIAL RESISTANCE; ALEXANDER PROJECT; UNITED-STATES; PROTEKT US AB Acute exacerbations of chronic bronchitis (AECB) are a major contributor to morbidity and mortality in patients with chronic obstructive pulmonary disease, accounting for more than 16 million physician office visits and over 500,000 hospitalizations in the USA each year. Antimicrobials have been recognized by clinical guidelines as an important component in the management of AECB with a bacterial etiology. The challenge of identifying patients most likely to benefit from antimicrobial therapy is difficult in the clinical setting. However, appropriate risk stratification of patients, and the use of antimicrobials within the correct spectrum and for a suitable duration, can improve clinical outcomes while minimizing induction of antimicrobial resistance. With an improved design in pharmacologic and clinical studies, differences can be appreciated among the various antimicrobial agents available to treat AECB. Factors to be considered in antimicrobial agent selection include local tissue penetration, effects on bacteriological eradication, duration of therapy, speed of resolution and prevention or delay of recurrences. C1 [Sethi, Sanjay] US Dept Vet Affairs, Western New York Healthcare Syst, VA Med Res 151, Buffalo, NY 14215 USA. [Sethi, Sanjay] SUNY Buffalo, Dept Med, Div Pulm & Crit Care Med, Buffalo, NY 14260 USA. RP Sethi, S (reprint author), US Dept Vet Affairs, Western New York Healthcare Syst, VA Med Res 151, 3495 Bailey Ave, Buffalo, NY 14215 USA. EM ssethi@buffalo.edu FU Bayer; Cornerstone; Glaxo Smith Kline; Mpex; Pfizer; Sanofi-Aventis; Schering; Schering-Plough, Corporation FX The author has received research support, honoraria or consulting fees from Bayer, Cornerstone, Glaxo Smith Kline, Mpex, Pfizer, Sanofi-Aventis and Schering. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.; The author would like to acknowledge the editorial assistance of Shabber Abbas in the preparation of this manuscript. Support for this assistance was provided by Schering-Plough, Corporation. The author accepts full responsibility for the construction and authorship of this manuscript. No other writing assistance was utilized in the production of this manuscript. NR 84 TC 5 Z9 6 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD APR PY 2010 VL 8 IS 4 BP 405 EP 417 DI 10.1586/ERI.09.133 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 592KT UT WOS:000277378500011 PM 20377336 ER PT J AU Espinoza, DO Boros, LG Crunkhorn, S Gami, H Patti, ME AF Espinoza, Daniel O. Boros, Laszlo G. Crunkhorn, Sarah Gami, Hiral Patti, Mary-Elizabeth TI Dual modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and-1 beta in cultured myotubes SO FASEB JOURNAL LA English DT Article DE metabolomics; fatty acid metabolism; lipid metabolism ID HUMAN SKELETAL-MUSCLE; INDUCED INSULIN-RESISTANCE; SATURATED FATTY-ACIDS; ERR-ALPHA; CERAMIDE SYNTHESIS; ENERGY-METABOLISM; GENE-EXPRESSION; ADIPOSE-TISSUE; OBESE SUBJECTS; PGC-1-ALPHA AB The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family is a key regulator of mitochondrial function, and reduced mRNA expression may contribute to muscle lipid accumulation in obesity and type 2 diabetes. To characterize the effects of PGC-1 on lipid metabolism, we overexpressed PGC-1 alpha and PGC-1 beta in C2C12 myotubes using adenoviral vectors. Both PGC-1 alpha and -1 beta increased palmitate oxidation [31% (P<0.01) and 26% (P<0.05), respectively] despite reductions in cellular uptake [by 6% (P<0.05) and 21% (P<0.001)]. Moreover, PGC-1 alpha and -1 beta increased mRNA expression of genes regulating both lipid oxidation (e.g., CPT1b and ACADL/M) and synthesis (FAS, CS, ACC1/2, and DGAT1). To determine the net effect, we assessed lipid composition in PGC-1-expressing cells. Total lipid content decreased by 42% in palmitate-loaded serum-starved cells overexpressing PGC-1 alpha (P<0.05). In contrast, in serum-replete cells, total lipid content was not significantly altered, but fatty acids C14:0, C16:0, C18:0, and C18: 1 were increased 2- to 4-fold for PGC-1 alpha/beta (P<0.05). Stable isotope-based dynamic metabolic profiling in serum-replete cells labeled with (13)C substrates revealed both increased de novo fatty acid synthesis from glucose and increased fatty acid synthesis by chain elongation with either PGC-1 alpha or -1 beta expression. These results indicate that PGC-1 can promote both lipid oxidation and synthesis, with net balance determined by the nutrient/hormonal environment.-Espinoza, D. O., Boros, L. G., Crunkhorn, S., Gami, H., Patti, M.-E. Dual Modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and -1 beta in cultured myotubes. FASEB J. 24, 1003-1014 (2010). www.fasebj.org C1 [Espinoza, Daniel O.; Crunkhorn, Sarah; Gami, Hiral; Patti, Mary-Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Espinoza, Daniel O.; Crunkhorn, Sarah; Gami, Hiral; Patti, Mary-Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. [Boros, Laszlo G.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Boros, Laszlo G.] SIDMAP LLC, Los Angeles, CA USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK062948]; Diabetes and Endocrinology Research Center [P30 DK36836] FX The authors thank Dr. Bruce Spiegelman (Dana Farber Cancer Institute, Boston, MA, USA) for the gift of adenovirus constructs Ad-GFP, AdPGC-1 alpha, and AdPGC-1 beta and Drs. Masa Katic, Yuji Yamamoto, and Enxuan Jing (Joslin Diabetes Center, Boston, MA, USA) for selected primers. The authors appreciate the assistance of the Lipid Core, Mouse Metabolic Phenotyping Center, Vanderbilt University (Nashville, TN, USA). The authors gratefully acknowledge grant funding from the National Institute of Diabetes and Digestive and Kidney Diseases (DK062948) and the Diabetes and Endocrinology Research Center (P30 DK36836). NR 55 TC 31 Z9 31 U1 2 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 IS 4 BP 1003 EP 1014 DI 10.1096/fj.09-133728 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 580PV UT WOS:000276462300008 PM 19906680 ER PT J AU Acevedo-Torres, K Torres-Ramos, CA Walter, CA Ayala-Torres, S AF Acevedo-Torres, Karina Torres-Ramos, Carlos A. Walter, Christi A. Ayala-Torres, Sylvette TI Age-Dependent Accumulation of Mitochondrial DNA Damage in Brain Tissues Derived from Apex1+/- Mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Acevedo-Torres, Karina] San Juan Bautista Sch Med, Dept Biochem, Caguas, PR USA. [Torres-Ramos, Carlos A.] Univ Puerto Rico, Dept Physiol, San Juan, PR 00936 USA. [Ayala-Torres, Sylvette] Univ Puerto Rico, Dept Pharmacol, San Juan, PR 00936 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Walter, Christi A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506622 ER PT J AU Arab, L Lonstreth, W O'Meara, E Mukamal, K Liebeskind, D AF Arab, Lenore Lonstreth, William O'Meara, Ellen Mukamal, Kenneth Liebeskind, David TI Tea, coffee and caffeinated drink consumption and risk of subclinical brain abnormalities on MRI SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Arab, Lenore] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lonstreth, William; O'Meara, Ellen] Univ Washington, Seattle, WA 98195 USA. [Mukamal, Kenneth] Beth Israel Deaconness Med Ctr, Boston, MA USA. [Liebeskind, David] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501760 ER PT J AU Bunni, MA Morinelli, TA Bell, PD Raymond, JR Garnovskaya, MN AF Bunni, Marlene A. Morinelli, Thomas A. Bell, Phillip D. Raymond, John R. Garnovskaya, Maria N. TI Bradykinin B2 receptor activates extracellular signal regulated kinase in renal cells from a mouse model of polycystic kidney disease SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bunni, Marlene A.; Morinelli, Thomas A.; Bell, Phillip D.; Raymond, John R.; Garnovskaya, Maria N.] Med Univ S Carolina, Charleston, SC 29425 USA. [Bunni, Marlene A.; Morinelli, Thomas A.; Bell, Phillip D.; Raymond, John R.; Garnovskaya, Maria N.] Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507264 ER PT J AU Chen, YX Gelfond, J McManus, LM Shireman, PK AF Chen, Yongxin Gelfond, Jonathan McManus, Linda M. Shireman, Paula K. TI MiRNA Expression Patterns during Skeletal Muscle Regeneration SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Chen, Yongxin; Gelfond, Jonathan; McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Chen, Yongxin; Shireman, Paula K.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500248 ER PT J AU Chu, KK Ide, T Brown-Endres, L Lee, SW AF Chu, Kiki Ide, Takao Brown-Endres, Lauren Lee, Sam W. TI GAMT, a p53-Inducible Modulator of Apoptosis, Is Critical for the Adaptive Response to Nutrient Stress SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501587 ER PT J AU Eichelsdoerfer, JL Evans, J Sorasaenee, K Morrison, C Linder, M Slaugenhaupt, S Cuajungco, MP AF Eichelsdoerfer, Jonathan Lee Evans, Jeffrey Sorasaenee, Karn Morrison, Chevaun Linder, Maria Slaugenhaupt, Susan Cuajungco, Math P. TI Trace metal dyshomeostasis is associated with loss of TRPML1 ion channel function SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Eichelsdoerfer, Jonathan Lee; Evans, Jeffrey; Sorasaenee, Karn; Morrison, Chevaun; Linder, Maria; Cuajungco, Math P.] Calif State Univ Fullerton, Fullerton, CA 92634 USA. [Slaugenhaupt, Susan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505515 ER PT J AU Ferruzzi, MG Ho, L Pasinetti, GM AF Ferruzzi, Mario G. Ho, Lap Pasinetti, Giulio M. TI Carotenoid levels in ageing human brain with reduced cognitive function SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Ferruzzi, Mario G.] Purdue Univ, W Lafayette, IN 47907 USA. [Ho, Lap] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Ho, Lap; Pasinetti, Giulio M.] James J Peters VA Med Ctr, Geriatr Res & Clin Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504033 ER PT J AU Ho, L Ferruzzi, MG Janle, EM Lobo, J Chen, TY Talcott, ST Simon, J Wu, QL Wang, J Cheng, A Weaver, CM Percival, SS Pasinetti, GM AF Ho, Lap Ferruzzi, Mario G. Janle, Elsa M. Lobo, Jessica Chen, Tzu-Ying Talcott, Stephen T. Simon, Jim Wu, Qing Li Wang, Jun Cheng, Alice Weaver, Connie M. Percival, Susan S. Pasinetti, Giulio Maria TI Bioavailability of grape-derived polyphenolics and implications in Alzheimer's disease prevention and therapy SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Ho, Lap; Wang, Jun; Cheng, Alice; Pasinetti, Giulio Maria] Mt Sinai Sch Med, New York, NY USA. [Ho, Lap; Pasinetti, Giulio Maria] James J Peters VA Med Ctr, GRECC, Bronx, NY USA. [Ferruzzi, Mario G.; Janle, Elsa M.; Lobo, Jessica; Chen, Tzu-Ying; Weaver, Connie M.] Purdue Univ, W Lafayette, IN 47907 USA. [Talcott, Stephen T.] Texas A&M Univ, College Stn, TX USA. [Simon, Jim; Wu, Qing Li] Rutgers State Univ, New Brunswick, NJ 08903 USA. [Percival, Susan S.] Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502736 ER PT J AU Hopson, KP Truelove, J Wang, YM Waeber, C AF Hopson, Kristen Park Truelove, Jessica Wang, Yumei Waeber, Christian TI S1P triggers cerebral vessel constriction through the store-operated calcium entry pathway SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hopson, Kristen Park; Truelove, Jessica; Wang, Yumei; Waeber, Christian] Massachusetts Gen Hosp, Charlestown, MA USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506807 ER PT J AU Hruby, A Jacques, PF Rumawas, ME Fox, CS Meigs, JB Troy, LM AF Hruby, Adela Jacques, Paul F. Rumawas, Marcella E. Fox, Caroline S. Meigs, James B. Troy, Lisa M. TI Mediterranean-Style Dietary Pattern and Incident Diabetes in the Framingham Heart Study Offspring SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hruby, Adela; Jacques, Paul F.; Rumawas, Marcella E.; Troy, Lisa M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Hruby, Adela; Jacques, Paul F.; Troy, Lisa M.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [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. [Fox, Caroline S.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502308 ER PT J AU Isayama, T Miyazono, S Okada, T Kono, M Crouch, R Zimmerman, A Makino, C AF Isayama, Tomoki Miyazono, Sadaharu Okada, Tetsuji Kono, Masahiro Crouch, Rosalie Zimmerman, Anita Makino, Clint TI Do vertebrate rhodopsins contain an allosteric binding site(s) for retinoids? SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Isayama, Tomoki; Miyazono, Sadaharu; Makino, Clint] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Okada, Tetsuji] Gakushuin Univ, Inst Biomol Sci, Tokyo 171, Japan. [Kono, Masahiro; Crouch, Rosalie] Med Univ S Carolina, Charleston, SC 29425 USA. [Zimmerman, Anita] Brown Univ, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507140 ER PT J AU Kolliputi, N Shaik, R Waxman, AB AF Kolliputi, Narasaiah Shaik, Rahamthulla Waxman, Aaron B. TI Suppressor of Cytokine Signaling-1 Inhibits Hyperoxic Induced Inflammasome Activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kolliputi, Narasaiah; Shaik, Rahamthulla; Waxman, Aaron B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. RI Kolliputi, Narasaiah/I-6050-2012 OI Kolliputi, Narasaiah/0000-0002-2654-1900 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502287 ER PT J AU La Bonte, LR Pavlov, V Takahashi, M Fujita, T Takahashi, K Stahl, GL AF La Bonte, Laura R. Pavlov, Vasile Takahashi, Minoru Fujita, Teizo Takahashi, Kazue Stahl, Gregory L. TI MBL-associated serine protease 1 (MASP-1) is necessary for thrombin substrate cleavage in vitro SO FASEB JOURNAL LA English DT Meeting Abstract C1 [La Bonte, Laura R.; Pavlov, Vasile; Stahl, Gregory L.] Harvard Univ, Sch Med, Boston, MA USA. [Takahashi, Minoru; Fujita, Teizo] Fukushima Med Univ, Fukushima, Japan. [Takahashi, Kazue] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500746 ER PT J AU Li, QG Babilonia, E Chang, MH Kwon, C Mandal, A Mercado, A Romero, MF Mount, DB AF Li, Qinggang Babilonia, Elisa Chang, Min-Hwang Kwon, Charles Mandal, Asim Mercado, Adriana Romero, Michael F. Mount, David B. TI A role for C-terminal cysteines in oligomerization of the Slc26a6 anion transporter SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Li, Qinggang; Babilonia, Elisa; Kwon, Charles; Mandal, Asim; Mercado, Adriana; Mount, David B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, Boston, MA 02115 USA. [Chang, Min-Hwang; Romero, Michael F.] Mayo Clin, Sch Med, Rochester, MN USA. [Mount, David B.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505097 ER PT J AU Londono, D Cadavid, D AF Londono, Diana Cadavid, Diego TI Bacterial lipoproteins can disseminate from the periphery to inflame the brain SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Londono, Diana; Cadavid, Diego] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507082 ER PT J AU Londono, D Cadavid, D AF Londono, Diana Cadavid, Diego TI Blood-brain barrier injury during spirochetal infection SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Londono, Diana; Cadavid, Diego] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504038 ER PT J AU Mercado, A Babilonia, E Gagnon, KB Mandal, A Delpire, E Mount, DB AF Mercado, Adriana Babilonia, Elisa Gagnon, Kenneth B. Mandal, Asim Delpire, Eric Mount, David B. TI C-Terminal threonines in the KCC4 K-Cl cotransporter confer sensitivity to cell volume SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Mercado, Adriana; Babilonia, Elisa; Mandal, Asim; Mount, David B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, Boston, MA 02115 USA. [Mercado, Adriana] Inst Nacl Cardiol Ignacio Chavez, Div Nephrol, Mexico City, DF, Mexico. [Gagnon, Kenneth B.; Delpire, Eric] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Mount, David B.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504768 ER PT J AU Morrow, AL Meinzen-Derr, J Huang, PW Schibler, KR Cahill, T Kallapur, SG Newburg, DS Tabangin, M Warner, BB Jiang, X AF Morrow, Ardythe L. Meinzen-Derr, Jareen Huang, Pengwei Schibler, Kurt R. Cahill, Tanya Kallapur, Suhas G. Newburg, David S. Tabangin, Meredith Warner, Barbara B. Jiang, Xi TI Secretor phenotype and genotype are novel predictors of severe outcomes in premature infants SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Morrow, Ardythe L.] Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Cincinnati, OH USA. [Meinzen-Derr, Jareen; Tabangin, Meredith] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH USA. [Huang, Pengwei; Jiang, Xi] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Schibler, Kurt R.; Cahill, Tanya; Kallapur, Suhas G.] Cincinnati Childrens Hosp Med Ctr, Div Neonatol, Cincinnati, OH USA. [Newburg, David S.] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA USA. [Warner, Barbara B.] Washington Univ, Div Neonatol, St Louis, MO USA. RI Meinzen-Derr, Jareen/N-4805-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500572 ER PT J AU Munn, LL Jain, A AF Munn, Lance L. Jain, Abhishek TI Determinants of Leukocyte Margination in Rectangular Microchannels SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Munn, Lance L.; Jain, Abhishek] Massachusetts Gen Hosp, Charlestown, MA USA. [Jain, Abhishek] Boston Univ, Boston, MA 02215 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505843 ER PT J AU Munn, LL Kamoun, W Tyrrell, JA AF Munn, Lance L. Kamoun, Walid Tyrrell, James Alex TI A mathematical framework for predicting oxygen transport and vessel remodeling in tumors SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Munn, Lance L.; Kamoun, Walid] Massachusetts Gen Hosp, Charlestown, MA USA. [Tyrrell, James Alex] Thomson Reuters, Rochester, NY USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505840 ER PT J AU Munn, LL Liao, S Wong, HK Lacorre, D di Tomaso, E Au, P Fukumura, D Jain, RK Cheng, G AF Munn, Lance L. Liao, Shan Wong, Hon Kit Lacorre, Delphine di Tomaso, Emmanuelle Au, Patrick Fukumura, Dai Jain, Rakesh K. Cheng, Gang TI Wrapping and Tapping Anastomosis between Engrafted Endothelial Networks and Host Vasculature SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Munn, Lance L.; Liao, Shan; Wong, Hon Kit; Lacorre, Delphine; di Tomaso, Emmanuelle; Au, Patrick; Fukumura, Dai; Jain, Rakesh K.; Cheng, Gang] Massachusetts Gen Hosp, Charlestown, MA USA. [di Tomaso, Emmanuelle] Novartis, Cambridge, MA USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504290 ER PT J AU Pasinetti, GM Chen, TY Janle, EM Cheng, A AF Pasinetti, Giulio Maria Chen, Tzu-Ying Janle, Elsa M. Cheng, Alice TI Role of Grape-Derived Polyphenols in the Prevention of Alzheimer's disease and the Promotion of Healthy Aging SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Pasinetti, Giulio Maria; Cheng, Alice] Mt Sinai Sch Med, New York, NY USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Chen, Tzu-Ying; Janle, Elsa M.] Purdue Univ, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505640 ER PT J AU Paunescu, TG Ljubojevic, M Russo, LM Winter, C McLaughlin, MM Wagner, CA Breton, S Brown, D AF Paunescu, Teodor G. Ljubojevic, Marija Russo, Leileata M. Winter, Christian McLaughlin, Margaret M. Wagner, Carsten A. Breton, Sylvie Brown, Dennis TI V-ATPase membrane accumulation and activity are stimulated by cAMP in A-type intercalated cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Paunescu, Teodor G.; Ljubojevic, Marija; Russo, Leileata M.; McLaughlin, Margaret M.; Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Ljubojevic, Marija; Russo, Leileata M.; McLaughlin, Margaret M.; Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Ljubojevic, Marija; Russo, Leileata M.; McLaughlin, Margaret M.; Breton, Sylvie; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Winter, Christian; Wagner, Carsten A.] Univ Zurich, Inst Physiol, Zurich, Switzerland. [Winter, Christian; Wagner, Carsten A.] Zurich Ctr Integrat Human Physiol, Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500236 ER PT J AU Pavlov, VI La Bonte, L Takahashi, K Stahl, GL AF Pavlov, Vasile I. La Bonte, Laura Takahashi, Kazue Stahl, Gregory L. TI The MBL-complex is necessary for FeCl3-mediated thrombosis SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Pavlov, Vasile I.; La Bonte, Laura; Stahl, Gregory L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Expt Therapeut & Reperfus Injury,Dept Anesthe, Boston, MA 02115 USA. [Takahashi, Kazue] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502484 ER PT J AU Sas, KM Janech, MG Amria, MY Stenbit, AE Bell, PD AF Sas, Kelli Margot Janech, Michael G. Amria, May Y. Stenbit, Antine E. Bell, P. Darwin TI Cilia movement represses mitogen-activated protein kinase signaling by enhancing expression of the raf kinase inhibitor protein SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Sas, Kelli Margot; Janech, Michael G.; Amria, May Y.; Stenbit, Antine E.; Bell, P. Darwin] Med Univ S Carolina, Charleston, SC 29425 USA. [Janech, Michael G.; Bell, P. Darwin] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505371 ER PT J AU Shum, WWC Da Silva, N Belleannee, C Ljubojevic, M Hill, E Brown, D Breton, S AF Shum, Winnie W. C. Da Silva, Nicolas Belleannee, Clemence Ljubojevic, Marija Hill, Eric Brown, Dennis Breton, Sylvie TI Actin cytoskeleton remodeling by RhoA and ROCKII regulates vacuolar H plus -ATPase (V-ATPase) recycling in epididymal clear cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Shum, Winnie W. C.; Da Silva, Nicolas; Belleannee, Clemence; Ljubojevic, Marija; Hill, Eric; Brown, Dennis; Breton, Sylvie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Program Membrane Biol,Nephrol Div, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504630 ER PT J AU Song, JW Munn, LL AF Song, Jonathan W. Munn, Lance L. TI Microfluidic Platform for Reproducing Blood Vessel Microenvironment SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Radiat Oncol Edwin L Steele Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501509 ER PT J AU Soto-Pina, AE Kadapakkam, S Mehring, C Hinojosa-Laborde, C Strong, R AF Soto-Pina, Alexandra Estela Kadapakkam, Sheela Mehring, Cynthia Hinojosa-Laborde, Carmen Strong, Randy TI Sympathectomy does not inhibit dexamethasone-induced hypertension SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Soto-Pina, Alexandra Estela; Kadapakkam, Sheela; Mehring, Cynthia; Hinojosa-Laborde, Carmen; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Soto-Pina, Alexandra Estela; Kadapakkam, Sheela; Strong, Randy] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501845 ER PT J AU Spagnolli, E Anderson, RR Hamblin, MR Nagasaka, Y Bloch, KD Zapol, WM AF Spagnolli, Ester Anderson, R. Rox Hamblin, Michael R. Nagasaka, Yasuko Bloch, Kenneth D. Zapol, Warren M. TI Protective effects of Red/Near Infrared Radiation on Murine Cardiac Ischemia/Reperfusion Injury SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Spagnolli, Ester; Nagasaka, Yasuko; Bloch, Kenneth D.; Zapol, Warren M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Spagnolli, Ester; Anderson, R. Rox; Hamblin, Michael R.; Nagasaka, Yasuko; Bloch, Kenneth D.; Zapol, Warren M.] Harvard Univ, Sch Med, Boston, MA USA. [Anderson, R. Rox; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507449 ER PT J AU Spiegelman, BM AF Spiegelman, Bruce M. TI Transcriptional Control of Brown Adipogenesis and Energy Homeostasis SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506058 ER PT J AU Torres-Ramos, CA Torres-Ortz, C Walter, C Ayala-Torres, S AF Torres-Ramos, Carlos A. Torres-Ortz, Ceidy Walter, Christi Ayala-Torres, Sylvette TI Apex1 haploinsufficiency leads to age-dependent increases in mtDNA lesions in liver SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Torres-Ramos, Carlos A.] Univ Puerto Rico, Dept Physiol, San Juan, PR 00936 USA. [Torres-Ramos, Carlos A.; Torres-Ortz, Ceidy; Ayala-Torres, Sylvette] Univ Puerto Rico, Dept Biochem, San Juan, PR 00936 USA. [Ayala-Torres, Sylvette] Univ Puerto Rico, Dept Pharmacol, San Juan, PR 00936 USA. [Walter, Christi] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Walter, Christi] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505663 ER PT J AU Tse, J Cheng, G Tyrrell, JA Wilcox-Adelman, SA Jain, RK Munn, LL AF Tse, Janet Cheng, Gang Tyrrell, James Alex Wilcox-Adelman, Sarah A. Jain, Rakesh K. Munn, Lance L. TI Compression-induced cell distension stimulates coordinated migration of mammary carcinoma cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Tse, Janet] MIT, Cambridge, MA 02139 USA. [Cheng, Gang; Tyrrell, James Alex; Jain, Rakesh K.; Munn, Lance L.] Massachusetts Gen Hosp, Charlestown, MA USA. [Tyrrell, James Alex] Thomson Reuters, Rochester, NY USA. [Wilcox-Adelman, Sarah A.] Boston Biomed Res Inst, Watertown, MA USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505864 ER PT J AU Wick, MJ Miller, YE Dempsey, EC AF Wick, Marilee J. Miller, York E. Dempsey, Edward C. TI Neprilysin Peptidase-Independent Complex Formation In Pulmonary Artery Smooth Muscle Cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wick, Marilee J.; Dempsey, Edward C.] Univ Colorado Denver, CVP Res, Med, Aurora, CO USA. [Miller, York E.] Univ Colorado Denver, Div Pulm, Aurora, CO USA. [Wick, Marilee J.; Miller, York E.; Dempsey, Edward C.] Denver VAMC, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506363 ER PT J AU Witczak, CA Toyoda, T Rockl, KSC Middelbeek, RJW Hirshman, MF Goodyear, LJ AF Witczak, Carol A. Toyoda, Taro Rockl, Katja S. C. Middelbeek, R. Jan-Willem Hirshman, Michael F. Goodyear, Laurie J. TI MARK4 is a Novel CaMKK alpha Substrate and Contraction-Regulated Kinase in Mouse Skeletal Muscle SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Witczak, Carol A.; Toyoda, Taro; Rockl, Katja S. C.; Middelbeek, R. Jan-Willem; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Metab Sect, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505150 ER PT J AU Moniz, RJ Chan, AM Gordon, LK Braun, J Arditi, M Kelly, KA AF Moniz, Raymond J. Chan, Ann M. Gordon, Lynn K. Braun, Jonathan Arditi, Moshe Kelly, Kathleen A. TI Plasmacytoid dendritic cells modulate nonprotective T-cell responses to genital infection by Chlamydia muridarum SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE Chlamydia muridarum; T regulatory cell; FoxP3; Th1 cell ID VIRAL-INFECTION; ANTIGEN; PATHOGENESIS; TOLERANCE; SECTIONS; FIBROSIS; DISEASE; MOUSE AB Given their immune-modulating capacity, regulatory T cells (Treg) cells may be important players in the induction of the protective T-cell response (Th1) to genital chlamydial infection. Recent work has demonstrated that plasmacytoid dendritic cells (pDC) respond to genital chlamydial infection, and that pDC may be uniquely positioned for the induction of Treg cells during this infection. Here, we present the first data demonstrating that Treg influx into the draining lymph node and the site of infection during genital chlamydial infection. We found that pDC depletion altered the numbers of Treg and nonprotective inflammatory cells [interferon gamma-(IFN gamma)-producing CD8+ T and IFN gamma-producing natural killer T cells] in the spleens of mice genitally infected with Chlamydia muridarum. Furthermore, pDC depletion did not alter Th1 cell numbers, indicating that pDC modulate cells that could inhibit and promote nonprotective inflammation during genital chlamydial infection. Finally, we demonstrate that depletion of pDC results in less severe dilation and collagen deposition in the oviduct following resolution of infection, implicating pDC activity in the formation of sequelae following genital C. muridarum infection. C1 [Moniz, Raymond J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Chan, Ann M.] Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA USA. [Gordon, Lynn K.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. [Gordon, Lynn K.] Greater Angeles Vet Affairs Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Braun, Jonathan; Kelly, Kathleen A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Braun, Jonathan] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [Braun, Jonathan] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. [Arditi, Moshe] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Div Pediat Crit Care, Los Angeles, CA 90048 USA. [Kelly, Kathleen A.] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA USA. RP Kelly, KA (reprint author), 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM kkelly@mednet.ucla.edu FU NIH [RO1 IA-026328, T32 AI107126-28, T32 AI52031] FX We would like to thank M. Colonna and M. Arditi for the generous gift of the mAb 927 antibody. This work was supported by NIH grants RO1 IA-026328 (K.A.K. and R.J.M.), T32 AI107126-28 (R.J.M.), and T32 AI52031 (R.J.M.). NR 23 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD APR PY 2010 VL 58 IS 3 BP 397 EP 404 DI 10.1111/j.1574-695X.2010.00653.x PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 567KX UT WOS:000275446600013 PM 20180848 ER PT J AU Flavin, R Peluso, S Nguyen, PL Loda, M AF Flavin, Richard Peluso, Stephane Nguyen, Paul L. Loda, Massimo TI Fatty acid synthase as a potential therapeutic target in cancer SO FUTURE ONCOLOGY LA English DT Review DE C75; cancer; ERBB-2; fatty acid synthase; MAPK; PI3K/AKT; SREBP-1 ID HER2/NEU ERBB-2 ONCOGENE; BREAST-CANCER; PROSTATE-CANCER; OVARIAN-CANCER; CELL-DEATH; EPIGALLOCATECHIN GALLATE; THIOESTERASE DOMAIN; ANTITUMOR-ACTIVITY; NATURAL INHIBITOR; CRYSTAL-STRUCTURE AB Fatty acid synthase (FASN) is a key enzyme involved in neoplastic lipogenesis. Overexpression of FASN is common in many cancers, and accumulating evidence suggests that it is a metabolic oncogene with an important role in tumor growth and survival, making it an attractive target for cancer therapy. Early small-molecule FASN inhibitors such as cerulenin, C75 and orlistat have been shown to induce apoptosis in several cancer cell lines and to induce tumor growth delay in several cancer xenograft models but their mechanism is still not well understood. These molecules suffer from pharmacological limitations and weight loss as a side effect that prevent their development as systemic drugs. Several potent inhibitors have recently been reported that may help to unravel and exploit the full potential of FASN as a target for cancer therapy in the near future. Furthermore, novel sources of FASN inhibitors, such as green tea and dietary soy, make both dietary manipulation and chemoprevention potential alternative modes of therapy in the future. C1 [Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Flavin, Richard] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Peluso, Stephane] Infin Pharmaceut, Cambridge, MA USA. [Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Loda, Massimo] Harvard & MIT, Broad Inst, Cambridge, MA USA. RP Loda, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu FU Prostate Cancer Foundation; National Cancer Institute [RO1CA131945, PO1CA89021, P50 CA90381]; Linda and Arthur Gelb Center for Translational Research; Dana Farber Cancer Institute-Novartis FX Support to Massimo Loda was obtained from the Prostate Cancer Foundation, the National Cancer Institute (RO1CA131945, PO1CA89021 and P50 CA90381), the Linda and Arthur Gelb Center for Translational Research, a gift from Nuclea Biomarkers to the Jimmy Fund and the Loda laboratory. Massimo Loda is the recipient of a grant from the Dana Farber Cancer Institute-Novartis Drug Development Program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 108 TC 159 Z9 167 U1 7 U2 48 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD APR PY 2010 VL 6 IS 4 BP 551 EP 562 DI 10.2217/FON.10.11 PG 12 WC Oncology SC Oncology GA 588JC UT WOS:000277064700014 PM 20373869 ER PT J AU Kanai, R Wakimoto, H Cheema, T Rabkin, SD AF Kanai, Ryuichi Wakimoto, Hiroaki Cheema, Tooba Rabkin, Samuel D. TI Oncolytic herpes simplex virus vectors and chemotherapy: are combinatorial strategies more effective for cancer? SO FUTURE ONCOLOGY LA English DT Review DE cancer drug; chemotherapeutics; combination therapy; herpes simplex virus; oncolytic virus; prodrug activation; virotherapy ID HISTONE DEACETYLASE INHIBITORS; SQUAMOUS-CELL CARCINOMA; MALIGNANT PLEURAL MESOTHELIOMA; TUMOR-SELECTIVE REPLICATION; ANTITUMOR EFFICACY; PANCREATIC-CANCER; IMMUNE-RESPONSES; BRAIN-TUMORS; GENE-THERAPY; COLORECTAL-CARCINOMA AB Despite aggressive treatments, including chemotherapy and radiotherapy, cancers often recur owing to resistance to conventional therapies. Oncolytic viruses such as oncolytic herpes simplex virus (oHSV) represent an exciting biological approach to cancer therapy. A range of viral mutations has been engineered into HSV to engender oncolytic activity. While oHSV as a single agent has been tested in a number of cancer clinical trials, preclinical studies have demonstrated enhanced efficacy when it is combined with cytotoxic anticancer drugs. Among the strategies that will be discussed in this article are combinations with standard-of-care chemotherapeutics, expression of prodrug-activating enzymes to enhance chemotherapy and small-molecule inhibitors. The combination of oHSV and chemotherapy can achieve much more efficient cancer cell killing than either single agent alone, often through synergistic interactions. This can be clinically important not just for improving efficacy but also for permitting lower and less toxic chemotherapeutic doses. The viral mutations in an oHSV vector often determine the favorability of its interactions with chemotherapy, just as different cancer cells, due to genetic alterations, vary in their response to chemotherapy. As chemotherapeutics are often the standard of care, combining them with an investigational new drug, such as oHSV, is clinically easier than combining multiple novel agents. As has become clear for most cancer therapies, multimodal treatments are usually more effective. In this article, we will discuss the recent progress of these combinatorial strategies between virotherapy and chemotherapy and future directions. C1 [Kanai, Ryuichi; Wakimoto, Hiroaki; Cheema, Tooba; Rabkin, Samuel D.] Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Boston, MA 02114 USA. [Kanai, Ryuichi; Wakimoto, Hiroaki; Cheema, Tooba; Rabkin, Samuel D.] Harvard Univ, Sch Med, Boston, MA USA. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Boston, MA 02114 USA. EM rabkin@helix.mgh.harvard.edu RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU National Institutes of Health; Department of Defense FX Our studies have been supported in part by grants from the National Institutes of Health and the Department of Defense. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 114 TC 30 Z9 32 U1 0 U2 10 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD APR PY 2010 VL 6 IS 4 BP 619 EP 634 DI 10.2217/FON.10.18 PG 16 WC Oncology SC Oncology GA 588JC UT WOS:000277064700018 PM 20373873 ER PT J AU Sandborn, WJ Korzenik, J Lashner, B Leighton, JA Mahadevan, U Marion, JF Safdi, M Sninsky, CA Patel, RM Friedenberg, KA Dunnmon, P Ramsey, D Kane, S AF Sandborn, William J. Korzenik, Joshua Lashner, Bret Leighton, Jonathan A. Mahadevan, Uma Marion, James F. Safdi, Michael Sninsky, Charles A. Patel, Raman M. Friedenberg, Keith A. Dunnmon, Preston Ramsey, David Kane, Sunanda TI Once-Daily Dosing of Delayed-Release Oral Mesalamine (400-mg Tablet) Is as Effective as Twice-Daily Dosing for Maintenance of Remission of Ulcerative Colitis SO GASTROENTEROLOGY LA English DT Article DE Ulcerative Colitis; Mesalamine; Maintenance; Controlled Trial ID 5-AMINOSALICYLIC ACID THERAPY; DAILY MMX MESALAZINE; HEALTHY-VOLUNTEERS; CONTROLLED TRIAL; DOUBLE-BLIND; DOUBLE-DUMMY; FORMULATIONS; MILD; NONADHERENCE; BALSALAZIDE AB BACKGROUND & AIMS: The practice of dosing mesalamines in divided doses for the treatment of ulcerative colitis (UC) began with sulfasalazine and was driven by sulfapyridine toxicity. This convention and the assumption that dosing multiple times a day is necessary to treat UC had not been challenged until recently. This study was conducted to determine the efficacy and safety of once-daily dosing of delayed-release mesalamine (Asacol 400-mg tablets) compared with twice-daily dosing for maintaining remission in UC patients. METHODS: A multicenter, randomized, investigator-blinded, 12-month, active-control trial was conducted to assess the noninferiority of delayed-release mesalamine 1.6-2.4 g/day administered once daily compared with twice daily in patients with mild-to-moderate UC currently in clinical remission. The primary end point was maintenance of clinical remission at month 6. RESULTS: A total of 1023 patients were randomized and dosed. The primary objective of noninferiority was met. At month 6, 90.5% of patients receiving once-daily dosing had maintained clinical remission, compared with 91.8% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -2.3 to 4.9). At month 12, 85.4% of patients receiving once-daily dosing had maintained clinical remission, compared with 85.4% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -4.6 to 4.7). Both regimens had low rates of withdrawals as a result of adverse events and serious adverse events. CONCLUSIONS: Once-daily dosing of delayed-release mesalamine at doses of 1.6-2.4 g/day was shown to be as effective as twice-daily dosing for maintenance of clinical remission in patients with UC. C1 [Sandborn, William J.] Mayo Clin, Inflammatory Bowel Dis Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA. [Korzenik, Joshua] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. [Korzenik, Joshua] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Lashner, Bret] Cleveland Clin, Inst Digest Dis, Cleveland, OH 44106 USA. [Leighton, Jonathan A.] Mayo Clin, Div Gastroenterol & Hepatol, Scottsdale, AZ USA. [Mahadevan, Uma] Univ Calif San Francisco, Ctr Colitis & Crohns Dis, San Francisco, CA 94143 USA. [Marion, James F.] Mt Sinai Sch Med, Dept Med, Div Gastroenterol, New York, NY USA. [Safdi, Michael] Ohio Gastroenterol & Liver Inst, Cincinnati, OH USA. [Sninsky, Charles A.] Digest Dis Associates, Gainesville, FL USA. [Patel, Raman M.] High Desert Gastroenterol Inc, Lancaster, CA USA. [Friedenberg, Keith A.] Great Lakes Gastroenterol, Mentor, OH USA. [Dunnmon, Preston; Ramsey, David] Procter & Gamble Pharmaceut Inc, Mason, OH USA. RP Sandborn, WJ (reprint author), Mayo Clin, Inflammatory Bowel Dis Clin, Div Gastroenterol & Hepatol, 200 1st St SW, Rochester, MN 55905 USA. EM sandborn.william@mayo.edu FU Procter & Gamble Pharmaceuticals, Inc, Mason, Ohio FX This study was funded by Procter & Gamble Pharmaceuticals, Inc, Mason, Ohio. ClinicalTrials. gov Identifier NCT00505778. NR 37 TC 39 Z9 41 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2010 VL 138 IS 4 BP 1286 EP U117 DI 10.1053/j.gastro.2009.12.054 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 575TP UT WOS:000276091800017 ER PT J AU Pino, MS Kikuchi, H Zeng, M Herraiz, MT Sperduti, I Berger, D Park, DY Iafrate, AJ Zukerberg, LR Chung, DC AF Pino, Maria S. Kikuchi, Hirotoshi Zeng, Min Herraiz, Maria-Teresa Sperduti, Isabella Berger, David Park, Do-Youn Iafrate, A. John Zukerberg, Lawrence R. Chung, Daniel C. TI Epithelial to Mesenchymal Transition Is Impaired in Colon Cancer Cells With Microsatellite Instability SO GASTROENTEROLOGY LA English DT Article DE Epithelial to Mesenchymal Transition; Microsatellite Instability; Colorectal Cancer; Transforming Growth Factor-beta Receptor Type II ID GROWTH-FACTOR-BETA; E-CADHERIN EXPRESSION; COLORECTAL-CANCER; CHROMOSOMAL INSTABILITY; METASTASIS; SMAD4; PLASTICITY; MUTATIONS; PROGNOSIS; PATHWAYS AB BACKGROUND & AIMS: Colorectal cancers (CRCs) displaying DNA microsatellite instability (MSI) are associated with a favorable natural history, but the molecular basis for this observation has not been defined. We sought to determine whether the epithelial to mesenchymal transition (EMT) is impaired in MSI-positive CRCs that characteristically have a mutant transforming growth factor-beta receptor type II (TGFBR2) gene. METHODS: The induction of EMT by transforming growth factor-beta 1 (TGF-beta 1) was analyzed by phase contrast microscopy, immunofluorescence, quantitative reverse transcription polymerase chain reaction, immunoblotting, and cellular migration, and invasion assays. Expression of EMT markers was evaluated by immunohistochemistry and quantitative reverse transcription polymerase chain reaction in a series of human colorectal tumors. RESULTS: TGF-beta 1 induced changes in cellular morphology, gene expression, motility, and invasion consistent with EMT in microsatellite stable (MSS) colon cancer cells, whereas cells with MSI and mutant TGFBR2 were unresponsive to TGF-beta 1. These effects did not require Smad4, but depended on the recruitment of extracellular signal-regulated kinase. Tumor cells with MSI but wild-type TGFBR2 underwent EMT in response to TGF-beta 1, indicating that TGFBR2 genotype is a key determinant of the EMT response in tumors with MSI. In human colorectal tumors, expression of EMT markers was significantly associated with adverse clinicopathologic features and the absence of MSI. CONCLUSIONS: These findings define a unique genotype-phenotype relationship between TGFBR2 and EMT that may contribute to the improved prognosis consistently observed in colon cancers with MSI. C1 [Pino, Maria S.; Kikuchi, Hirotoshi; Zeng, Min; Herraiz, Maria-Teresa; Chung, Daniel C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Berger, David] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Park, Do-Youn; Iafrate, A. John; Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Pino, Maria S.] Regina Elena Inst Canc Res, Dept Med Oncol, Rome, Italy. [Park, Do-Youn] Pusan Natl Univ, Sch Med, Dept Pathol, Pusan, South Korea. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 50 Blossom St, Boston, MA 02114 USA. EM dchung@partners.org RI Sperduti, Isabella /K-8902-2016 OI Sperduti, Isabella /0000-0001-5115-3099 FU MGH ECOR Fund for Medical Discovery; National Institutes of Health [CA92594]; [P50 CA127003] FX M. S. P. was supported by the MGH ECOR Fund for Medical Discovery; D. C. C. was supported in part by National Institutes of Health CA92594; support also provided by P50 CA127003 and the Kate J. and Dorothy L. Clapp Fund. NR 33 TC 44 Z9 47 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2010 VL 138 IS 4 BP 1406 EP 1417 DI 10.1053/j.gastro.2009.12.010 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 575TP UT WOS:000276091800030 PM 20026115 ER PT J AU Shaheen, NJ Greenwald, BD Peery, AF Dumot, JA Nishioka, NS Wolfsen, HC Burdick, JS Abrams, JA Wang, KK Mallat, D Johnston, MH Zfass, AM Smith, JO Barthel, JS Lightdale, CJ AF Shaheen, Nicholas J. Greenwald, Bruce D. Peery, Anne F. Dumot, John A. Nishioka, Norman S. Wolfsen, Herbert C. Burdick, J. Steven Abrams, Julian A. Wang, Kenneth K. Mallat, Damien Johnston, Mark H. Zfass, Alvin M. Smith, Jenny O. Barthel, James S. Lightdale, Charles J. TI Safety and efficacy of endoscopic spray cryotherapy for Barrett's esophagus with high-grade dysplasia SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID RADIOFREQUENCY ABLATION; PHOTODYNAMIC THERAPY; FOLLOW-UP; ADENOCARCINOMA; REGISTRY AB Background: Endoscopic ablation to treat Barrett's esophagus (BE) with high-grade dysplasia (HGD) is associated with a decreased incidence of esophageal adenocarcinoma. Endoscopic spray cryotherapy (CRYO) demonstrates promising preliminary data. Objective: To assess the safety and efficacy of CRY in BE with HGD. Design: Multicenter, retrospective cohort study. Setting: Nine academic and community centers; treatment period, 2007 to 2009. Patients: Subjects with HGD confirmed by 2 pathologists. Previous EMR was allowed if residual HGD remained. Interventions: CRYO with follow-up biopsies. Main Outcome Measurements: Complete eradication of HGD with persistent low-grade dysplasia, complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and complete eradication of all intestinal metaplasia. Results: Ninety-eight subjects (mean age 65.4 years, 83% male) with BE and HGD (mean length 5.3 cm) underwent 333 treatments (mean 3.4 treatments per subject). There were no esophageal perforations. Strictures developed in 3 subjects. Two subjects reported severe chest pain managed with oral narcotics. One subject was hospitalized for bright red blood per rectum. Sixty subjects had completed all planned CRY treatments and were included in the efficacy analysis. Fifty-eight subjects (97%) had complete eradication of HGD, 52 (87%) had complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and 34 (57%) had complete eradication of all intestinal metaplasia. Subquamous BE was found in 2 subjects (3%). Limitations: Nonrandomized, retrospective study with no control group, short follow-up (10.5 months), lack of centralized pathology, and use of surrogate outcome for decreased cancer risk. Conclusions: CRYO is a safe and well-tolerated therapy for BE and HGD. Short-term results suggest that CRY is highly effective in eradicating HGD. (Gastrointest Enclose 2010;71:680-5.) C1 [Shaheen, Nicholas J.; Peery, Anne F.] Univ N Carolina, Sch Med, Ctr Esophageal Dis & Swallowing, Chapel Hill, NC 27599 USA. [Greenwald, Bruce D.] Univ Maryland, Sch Med, Div Gastroenterol & Hepatol, Baltimore, MD 21201 USA. Greenebaum Canc Ctr, Baltimore, MD USA. [Dumot, John A.] Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA. [Nishioka, Norman S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wolfsen, Herbert C.] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Burdick, J. Steven; Mallat, Damien] Texas Digest Hlth Associates, Dallas, TX USA. [Abrams, Julian A.; Lightdale, Charles J.] Columbia Univ, Med Ctr, New York, NY USA. [Wang, Kenneth K.] Mayo Clin, Rochester, MN USA. [Johnston, Mark H.] Lancaster Gastroenterol Inc, Lancaster, PA USA. [Zfass, Alvin M.; Smith, Jenny O.] Virginia Commonwealth Univ, Richmond, VA USA. [Barthel, James S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. RP Shaheen, NJ (reprint author), Univ N Carolina, Sch Med, Ctr Esophageal Dis & Swallowing, CB 7080, Chapel Hill, NC 27599 USA. RI Shaheen, Nicholas/A-1898-2013 FU CSA Medical; BARRX Medical Inc; National Institutes of Health [T32 DK 07634, P30 DK034987]; National Cancer Institute [CA 132892] FX The following authors disclosed financial relationships relevant to this publication: N.J. Shaheen: Grant from. consultant for. and advisory committee member of CSA Medical: grant from BARRX Medical Inc. B.D. Greenwald: Consultant for and advisory committee member of CSA Medical. N.S. Nishioka: Research support from CSA Medical. H.C. wolfsen: Research support from CSA Medical: research support from BARRX Medical Inc. K.K. wang; Research support from CSA Medical: research support from BARRX Medical Inc. M.H. Johnston: Research support from CSA Medical. J.S. Barthel: Research support from CSA Medical. C.J. Lightdale: Advisory committee member of CSA Medical. All other authors disclosed no financial relationships relevant to this publication. This study was funded in part with a grant from CSA Medical, makers of the spray cryotherapy device. Dr. Peery is supported by a grant from the National Institutes of Health (T32 DK 07634). Statistical analysis and data management were also supported by a grant from the National Institutes of Health (P30 DK034987). Dr. Abrams is supported in part by a K07 award from the National Cancer Institute (CA 132892). NR 18 TC 99 Z9 100 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2010 VL 71 IS 4 BP 680 EP 685 DI 10.1016/j.gie.2010.01.018 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 580LE UT WOS:000276449000003 PM 20363409 ER PT J AU Greenwald, BD Dumot, JA Abrams, JA Lightdale, CJ David, DS Nishioka, NS Yachimski, P Johnston, MH Shaheen, NJ Zfass, AM Smith, JO Gill, KRS Burdick, JS Mallat, D Wolfsen, HC AF Greenwald, Bruce D. Dumot, John A. Abrams, Julian A. Lightdale, Charles J. David, Donald S. Nishioka, Norman S. Yachimski, Patrick Johnston, Mark H. Shaheen, Nicholas J. Zfass, Alvin M. Smith, Jenny O. Gill, Kanwar Rupinder S. Burdick, J. Steven Mallat, Damien Wolfsen, Herbert C. TI Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; DEFINITIVE CHEMORADIOTHERAPY; BARRETTS-ESOPHAGUS; PHOTODYNAMIC THERAPY; RADIATION PROCTITIS; MUCOSAL RESECTION; SALVAGE TREATMENT; EARLY NEOPLASIA; LOCAL FAILURE; SURGERY AB Background: Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. Objective: To assess the safety and efficacy of cryotherapy in esophageal carcinoma. Design: Multicenter, retrospective cohort study. Setting: Ten academic and community medical centers between 2006 and 2009. Patients: Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. Interventions: Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. Main Outcome Measurements: Complete eradication of luminal cancer and adverse events. Results: Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Pony-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosa! cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10(13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. Limitations: Retrospective study design, short follow-up. Conclusions: Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer. (Gastrointest Enclose 2010;71:686-93.) C1 [Greenwald, Bruce D.] Univ Maryland, Sch Med, Div Gastroenterol & Hepatol, Baltimore, MD 21201 USA. Greenebaum Canc Ctr, Baltimore, MD USA. [Dumot, John A.] Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA. [Abrams, Julian A.; Lightdale, Charles J.] Columbia Univ, Med Ctr, New York, NY USA. [David, Donald S.] City Hope Natl Med Ctr, Dept Gastroenterol, Duarte, CA USA. [Nishioka, Norman S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nishioka, Norman S.] Harvard Univ, Sch Med, Boston, MA USA. [Yachimski, Patrick] Vanderbilt Univ, Med Ctr, Div Gastroenterol Hepatol & Nutr, Nashville, TN USA. [Johnston, Mark H.] Lancaster Gastroenterol Inc, Lancaster, PA USA. [Shaheen, Nicholas J.] Univ N Carolina, Sch Med, Ctr Esophageal Dis & Swallowing, Chapel Hill, NC USA. [Zfass, Alvin M.; Smith, Jenny O.] Virginia Commonwealth Univ, Richmond, VA USA. [Gill, Kanwar Rupinder S.] Sutter Gould Med Fdn, Modesto, CA USA. [Wolfsen, Herbert C.] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Burdick, J. Steven] Digest Hlth Consultants, Dallas, TX USA. [Mallat, Damien] Digest Hlth Associates Texas, Dallas, TX USA. RP Greenwald, BD (reprint author), Univ Maryland, Sch Med, Div Gastroenterol & Hepatol, 22 S Greene St,Room N3W62, Baltimore, MD 21201 USA. RI Shaheen, Nicholas/A-1898-2013 FU CSA Medical; BARRX Medical Inc; Oncoscope Inc FX The following authors disclosed financial relationships relevant to this publication: B.D. Greenwald: Research grant from. consultant for, and advisory committee member of CSA Medical. J.A. Dumot: Research grant from and advisory committee member of CSA Medical. C.J. Lightdale: Advisory committee member of CSA Medical; research support from BARRX Medical Inc; research grant from, consultant for, and speaker for proctor & Gamble; research grant from Oncoscope Inc; research grant from and consultant for Takeda pharmaceuticals. All other authors disclosed no financial relationships relevant to this publication. CSA Medical supported this study through a grant for statistical analysis and by assisting in data collection at some sites. CSA Medical had no role in study design, analysis, interpretation of the data, or in writing the report. NR 35 TC 52 Z9 52 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2010 VL 71 IS 4 BP 686 EP 693 DI 10.1016/j.gie.2010.01.042 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 580LE UT WOS:000276449000004 PM 20363410 ER PT J AU Karaca, C Turner, BG Cizginer, S Forcione, D Brugge, W AF Karaca, Cetin Turner, Brian G. Cizginer, Sevdenur Forcione, David Brugge, William TI Accuracy of EUS in the evaluation of small gastric subepithelial lesions SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID GASTROINTESTINAL SUBMUCOSAL LESIONS; FINE-NEEDLE ASPIRATION; ENDOSCOPIC ULTRASONOGRAPHY; STROMAL TUMORS; DIAGNOSIS; RESECTION; TRACT; ENDOSONOGRAPHY; MASSES; YIELD AB Background: EUS combined with endoluminal resection techniques is increasingly used to provide a definitive diagnosis of small gastric subepithelial lesions seen on standard upper endoscopy. Objective: To evaluate the accuracy of EUS in diagnosing small gastric subepithelial lesions by using histology as the criterion standard. Design: A retrospective study Setting: Academic tertiary care center. Patients: A total of 22 patients (15 women, mean age 62.2 years) with an endoscopically resected gastric subepithelial lesion were included in this 3-year retrospective study. Main Outcome Measurements: The size, echogenicity the layer of origin, and presumptive diagnosis were determined by EUS. The diagnostic accuracy of EUS was determined by using histology as the criterion standard. Results: The mean size of the 22 lesions was 13.6 mm (range 8-20 mm). An endoscopic cap band mucosectomy device was used to resect 16 (72.7%) lesions, whereas 6 (27.3%) were resected with a saline solution assisted and snare technique. Using histology as a criterion standard, we found that the accuracy of the EUS diagnosis was 10 of 22 (45.5%). EUS alone had an accuracy rate of 30.8% and 66.7%, respectively in the diagnosis of neoplastic and non-neoplastic lesions. Limitations: A single-center, retrospective analysis. Conclusion: EUS imaging had a low accuracy rate in the diagnosis of gastric subepithelial lesions, and endoscopic submucosal resection should be performed to provide a histologic diagnosis. Resection of small subepithelial lesions of 20 mm or less can be accomplished en bloc with an endoscopic cap band mucosectomy device. (Gastrointest Endosc 2010;71722-7.) C1 [Karaca, Cetin; Turner, Brian G.; Cizginer, Sevdenur; Forcione, David; Brugge, William] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, W (reprint author), 55 Fruit St,Blake 4, Boston, MA 02114 USA. NR 24 TC 46 Z9 55 U1 2 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2010 VL 71 IS 4 BP 722 EP 727 DI 10.1016/j.gie.2009.10.019 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 580LE UT WOS:000276449000011 PM 20171632 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Inflationary caution in GI endoscopy SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID COLONOSCOPY; TIME C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2010 VL 71 IS 4 BP 789 EP 791 DI 10.1016/j.gie.2009.12.044 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 580LE UT WOS:000276449000021 PM 20363420 ER PT J AU Rattner, DW AF Rattner, David W. TI Laying the foundation for NOTES: another brick in the wall SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID CHOLECYSTECTOMY C1 Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2010 VL 71 IS 4 BP 842 EP 843 DI 10.1016/j.gie.2009.12.034 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 580LE UT WOS:000276449000031 PM 20363427 ER PT J AU Flicker, MS Weber, HC AF Flicker, Michael S. Weber, H. Christian TI Endoscopic hemostasis in a case of bleeding from Zenker's diverticulum SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID MANAGEMENT C1 [Weber, H. Christian] VA Boston Healthcare Syst, Gastroenterol Sect, Med Serv, Jamaica Plain, MA 02130 USA. RP Weber, HC (reprint author), VA Boston Healthcare Syst, Gastroenterol Sect, Med Serv, Room 6A-46,150 S Huntington Ave, Jamaica Plain, MA 02130 USA. NR 15 TC 4 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2010 VL 71 IS 4 BP 869 EP 871 DI 10.1016/j.gie.2009.09.021 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 580LE UT WOS:000276449000044 PM 19922922 ER PT J AU Berger, MF Levin, JZ Vijayendran, K Sivachenko, A Adiconis, X Maguire, J Johnson, LA Robinson, J Verhaak, RG Sougnez, C Onofrio, RC Ziaugra, L Cibulskis, K Laine, E Barretina, J Winckler, W Fisher, DE Getz, G Meyerson, M Jaffe, DB Gabriel, SB Lander, ES Dummer, R Gnirke, A Nusbaum, C Garraway, LA AF Berger, Michael F. Levin, Joshua Z. Vijayendran, Krishna Sivachenko, Andrey Adiconis, Xian Maguire, Jared Johnson, Laura A. Robinson, James Verhaak, Roel G. Sougnez, Carrie Onofrio, Robert C. Ziaugra, Liuda Cibulskis, Kristian Laine, Elisabeth Barretina, Jordi Winckler, Wendy Fisher, David E. Getz, Gad Meyerson, Matthew Jaffe, David B. Gabriel, Stacey B. Lander, Eric S. Dummer, Reinhard Gnirke, Andreas Nusbaum, Chad Garraway, Levi A. TI Integrative analysis of the melanoma transcriptome SO GENOME RESEARCH LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; CHRONIC MYELOGENOUS LEUKEMIA; GENE FUSIONS; MULTIPLEX AMPLIFICATION; MALIGNANT-MELANOMA; GENOMIC ANALYSES; LUNG-CANCER; RNA-SEQ; MUTATIONS; IDENTIFICATION AB Global studies of transcript structure and abundance in cancer cells enable the systematic discovery of aberrations that contribute to carcinogenesis, including gene fusions, alternative splice isoforms, and somatic mutations. We developed a systematic approach to characterize the spectrum of cancer-associated mRNA alterations through integration of transcriptomic and structural genomic data, and we applied this approach to generate new insights into melanoma biology. Using paired-end massively parallel sequencing of cDNA (RNA-seq) together with analyses of high-resolution chromosomal copy number data, we identified 11 novel melanoma gene fusions produced by underlying genomic rearrangements, as well as 12 novel readthrough transcripts. We mapped these chimeric transcripts to base-pair resolution and traced them to their genomic origins using matched chromosomal copy number information. We also used these data to discover and validate base-pair mutations that accumulated in these melanomas, revealing a surprisingly high rate of somatic mutation and lending support to the notion that point mutations constitute the major driver of melanoma progression. Taken together, these results may indicate new avenues for target discovery in melanoma, while also providing a template for large-scale transcriptome studies across many tumor types. C1 [Berger, Michael F.; Levin, Joshua Z.; Vijayendran, Krishna; Sivachenko, Andrey; Adiconis, Xian; Maguire, Jared; Johnson, Laura A.; Robinson, James; Verhaak, Roel G.; Sougnez, Carrie; Onofrio, Robert C.; Ziaugra, Liuda; Cibulskis, Kristian; Barretina, Jordi; Winckler, Wendy; Getz, Gad; Meyerson, Matthew; Jaffe, David B.; Gabriel, Stacey B.; Lander, Eric S.; Gnirke, Andreas; Nusbaum, Chad; Garraway, Levi A.] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA. [Vijayendran, Krishna; Johnson, Laura A.; Verhaak, Roel G.; Meyerson, Matthew; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Laine, Elisabeth; Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol & Cutaneous Biol, Res Ctr, Boston, MA 02114 USA. [Fisher, David E.] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02199 USA. [Fisher, David E.] Childrens Hosp, Boston, MA 02199 USA. [Meyerson, Matthew; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02142 USA. [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Garraway, LA (reprint author), MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA. EM Levi_Garraway@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU Novartis Institutes of Biomedical Research; Starr Cancer Consortium; Adelson Medical Research Foundation FX We thank Cory Johannessen, Gordon Saksena, Scott Carter, William Lin, Carsten Russ, Jim Bochicchio, and the staff of the Broad Institute Biological Samples Platform, Genome Analysis Platform, and Genome Sequencing Platform. We thank the Novartis Institute of BioMedical Research and the Genomics Institute of the Novartis Research Foundation for providing RNA from melanoma cell lines. This work was funded by grants from the Novartis Institutes of Biomedical Research, the Starr Cancer Consortium, and the Adelson Medical Research Foundation. NR 67 TC 159 Z9 162 U1 1 U2 19 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD APR PY 2010 VL 20 IS 4 BP 413 EP 427 DI 10.1101/gr.103697.109 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 577PK UT WOS:000276236100002 PM 20179022 ER PT J AU Ozsolak, F Goren, A Gymrek, M Guttman, M Regev, A Bernstein, BE Milos, PM AF Ozsolak, Fatih Goren, Alon Gymrek, Melissa Guttman, Mitchell Regev, Aviv Bernstein, Bradley E. Milos, Patrice M. TI Digital transcriptome profiling from attomole-level RNA samples SO GENOME RESEARCH LA English DT Article ID MULTIPLE DISPLACEMENT AMPLIFICATION; WHOLE GENOME AMPLIFICATION; PLURIPOTENT STEM-CELLS; GENE-EXPRESSION; SINGLE-CELL; ANTISENSE TRANSCRIPTS; CDNA SYNTHESIS; DNA; BIAS; PCR AB Accurate profiling of minute quantities of RNA in a global manner can enable key advances in many scientific and clinical disciplines. Here, we present low-quantity RNA sequencing (LQ-RNAseq), a high-throughput sequencing- based technique allowing whole transcriptome surveys from subnanogram RNA quantities in an amplification/ligation-free manner. LQ-RNAseq involves first-strand cDNA synthesis from RNA templates, followed by 3' polyA tailing of the single-stranded cDNA products and direct single molecule sequencing. We applied LQ-RNAseq to profile S. cerevisiae polyA+transcripts, demonstrate the reproducibility of the approach across different sample preparations and independent instrument runs, and establish the absolute quantitative power of this method through comparisons with other reported transcript profiling techniques and through utilization of RNA spike-in experiments. We demonstrate the practical application of this approach to define the transcriptional landscape of mouse embryonic and induced pluripotent stem cells, observing transcriptional differences, including over 100 genes exhibiting differential expression between these otherwise very similar stem cell populations. This amplification-independent technology, which utilizes small quantities of nucleic acid and provides quantitative measurements of cellular transcripts, enables global gene expression measurements from minute amounts of materials and offers broad utility in both basic research and translational biology for characterization of rare cells. C1 [Ozsolak, Fatih; Milos, Patrice M.] Helicos BioSci Corp, Cambridge, MA 02139 USA. [Goren, Alon; Gymrek, Melissa; Guttman, Mitchell; Regev, Aviv; Bernstein, Bradley E.] Harvard & MIT, Broad Inst, Cambridge, MA 02142 USA. [Goren, Alon; Gymrek, Melissa; Regev, Aviv; Bernstein, Bradley E.] Howard Hughes Med Inst, Boston, MA 02114 USA. [Goren, Alon; Gymrek, Melissa; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Goren, Alon; Gymrek, Melissa; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Regev, Aviv] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Ozsolak, F (reprint author), Helicos BioSci Corp, Cambridge, MA 02139 USA. EM fatihozsolak@gmail.com; pmilos@helicosbio.com OI /0000-0002-6086-3903 FU EMBO; Merkin Foundation; Charles E.Culpeper Medical; Howard Hughes Medical Institute; Burroughs Wellcome Fund; HHMI; National Human Genome Research Institute FX We thank Chris Hart, Kristen Kerouac, Daniel Jones, and Erik Hansen for technical assistance and discussions. A.G. is supported by an EMBO long-term postdoctoral fellowship. A.R. is an investigator of the Merkin Foundation for Stem Cell Research at the Broad Institute. B.E.B. is a Charles E.Culpeper Medical Scholar. A.R.and B.E.B.are Early Career Scientists of the Howard Hughes Medical Institute.This research was supported by funds from the Burroughs Wellcome Fund (B.E.B., A.R.), HHMI, and the National Human Genome Research Institute. NR 34 TC 32 Z9 33 U1 0 U2 10 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD APR PY 2010 VL 20 IS 4 BP 519 EP 525 DI 10.1101/gr.102129.109 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 577PK UT WOS:000276236100013 PM 20133332 ER PT J AU Martinez-Augustin, O Lopez-Posadas, R Gonzalez, R Ballester, I Suarez, MD Zarzuelo, A de Medina, FS AF Martinez-Augustin, Olga Lopez-Posadas, Rocio Gonzalez, Raquel Ballester, Isabel Dolores Suarez, Maria Zarzuelo, Antonio Sanchez de Medina, Fermin TI It may not be intestinal, but tissue non-specific alkaline phosphatase SO GUT LA English DT Letter C1 [Martinez-Augustin, Olga; Lopez-Posadas, Rocio; Gonzalez, Raquel; Dolores Suarez, Maria; Zarzuelo, Antonio; Sanchez de Medina, Fermin] Univ Granada, Sch Pharm, Dept Biochem & Mol Biol 2, CIBERehd, E-18071 Granada, Spain. [Martinez-Augustin, Olga; Lopez-Posadas, Rocio; Gonzalez, Raquel; Dolores Suarez, Maria; Zarzuelo, Antonio; Sanchez de Medina, Fermin] Univ Granada, Sch Pharm, Dept Pharmacol, CIBERehd, E-18071 Granada, Spain. [Ballester, Isabel] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP de Medina, FS (reprint author), Univ Granada, Sch Pharm, Dept Biochem & Mol Biol 2, CIBERehd, Campus Cartuja S-N, E-18071 Granada, Spain. EM fsanchez@ugr.es RI Zarzuelo, Antonio/L-2840-2014; Lorente, M Dolores/N-1313-2014; Suarez Ortega, Maria Dolores/H-1240-2015; Martinez Augustin, Olga/K-6720-2014; OI Suarez Ortega, Maria Dolores/0000-0003-3197-2518; Martinez Augustin, Olga/0000-0001-8291-3468; Sanchez de Medina, Fermin/0000-0002-4516-5824 NR 4 TC 3 Z9 3 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 2010 VL 59 IS 4 BP 560 EP 560 DI 10.1136/gut.2009.191957 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 573GZ UT WOS:000275898400026 PM 20332532 ER PT J AU Subramanian, S Yajnik, V Sands, B Cullen, G Korzenik, JR AF Subramanian, S. Yajnik, V. Sands, B. Cullen, G. Korzenik, J. R. TI CHARACTERISATION AND OUTCOME OF PATIENTS WITH INFLIXIMAB INDUCED LUPUS ERYTHEMATOSUS AND RETREATMENT WITH A SECOND ANTI-TUMOUR NECROSIS FACTOR AGENT SO GUT LA English DT Meeting Abstract CT Annual General Meeting of the British-Society-of-Gastroenterology CY MAR 22-25, 2010 CL Liverpool, ENGLAND SP British Soc Gastroenterol C1 [Subramanian, S.] Royal Liverpool Univ Hosp, Dept Gastroenterol, Liverpool, Merseyside, England. [Yajnik, V.; Sands, B.; Cullen, G.; Korzenik, J. R.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 2010 VL 59 SU 1 BP A4 EP A4 DI 10.1136/gut.2009.208934i PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 577ZT UT WOS:000276263700010 ER PT J AU Mercado, C Zingmond, D Karlan, BY Sekaris, E Gross, J Maggard-Gibbons, M Tomlinson, JS Ko, CY AF Mercado, Cheryl Zingmond, David Karlan, Beth Y. Sekaris, Evan Gross, Jenny Maggard-Gibbons, Melinda Tomlinson, James S. Ko, Clifford Y. TI Quality of care in advanced ovarian cancer: The importance of provider specialty SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Outcomes; Quality of life ID ACHIEVING EXCELLENT OUTCOMES; HOSPITAL VOLUME; SURGEON VOLUME; COLORECTAL RESECTION; EXPERIENCE; CARCINOMA; SURROGATE; INDEX; SERVE AB Background. One of the cornerstones of ovarian cancer therapy is cytoreductive surgery, which can be performed by surgeons with different specialty training. We examined whether surgeon specialty impacts quality of life (as proxied by presence of ostomy) and overall survival for women with advanced ovarian cancer. Methods. Stage IIIC/IV ovarian cancer patients were identified using 4 state cancer registries: California, Washington, New York, and Florida and linked records to the corresponding inpatient-hospital discharge file, AMA Masterfile, and 2000 U.S. Census SF4 File. Predictors of receipt of care by a general surgeon and creation of fecal ostomy were analyzed. Multivariate modeling was performed to assess the association of hospital volume (low volume (LV) [0-4 cases], middle volume (MV) [5-9], high volume (HV) [10-19], and very high volume (VHV) [20+]) and surgeon specialty training (gynecologic oncologists/gynecologists, general surgeons, and other specialty) on survival. Results. We identified 31,897 Stage IIIC/IV patients; mean age was 64 years. Treatment of patients by a general surgeon was predicted by LV, rural patient residence, poverty, and high level of comorbidity. Patients had lower hazard of death when treated in higher volume hospitals as compared to LV [VHV hazard ratio (HR) = 0.79, P<.0001; HV HR = 0.89, P<0.001]. Patients treated by a general surgeon had higher likelihood of an ostomy (OR = 4.46, P<.0001) and hazard of death (HR = 1.63, P<.0001) compared to gynecologic oncologist/gynecologist. Conclusions. Advanced stage ovarian cancer patients have better survival when treated by gynecologic oncology/gynecology trained surgeons. Data suggest that referral to these specialists may optimize surgical debulking and minimize the creation of a fecal ostomy. (C) 2010 Elsevier Inc. All rights reserved. C1 [Mercado, Cheryl; Zingmond, David; Sekaris, Evan; Maggard-Gibbons, Melinda; Tomlinson, James S.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Karlan, Beth Y.; Gross, Jenny] Cedars Sinai Med Ctr, Div Gynecol Oncol, Womens Canc Res Inst, Los Angeles, CA 90048 USA. [Maggard-Gibbons, Melinda] Olive View UCLA, Dept Surg, Sylmar, CA 91342 USA. [Tomlinson, James S.; Ko, Clifford Y.] VA Greater Angeles Los Healthcare Syst, Dept Surg, Los Angeles, CA 90073 USA. RP Ko, CY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 72-215 Ctr Hlth Sci,Box 956904, Los Angeles, CA 90095 USA. EM cko@mednet.ucla.edu RI Lester, Jenny/B-5933-2012 FU Centers for Disease Control; American Cancer Society FX This work was supported by the Centers for Disease Control and the American Cancer Society. NR 24 TC 38 Z9 38 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2010 VL 117 IS 1 BP 18 EP 22 DI 10.1016/j.ygyno.2009.12.033 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 582JV UT WOS:000276594200004 PM 20106512 ER PT J AU Ayata, C AF Ayata, Cenk TI Cortical Spreading Depression Triggers Migraine Attack: Pro SO HEADACHE LA English DT Review ID CEREBRAL BLOOD-FLOW; ASTROCYTE CALCIUM WAVES; CLASSIC MIGRAINE; TRIGEMINAL NUCLEUS; XE-133 INHALATION; ANESTHETIZED CAT; BRAIN; MECHANISMS; CORTEX; HYPOPERFUSION AB More than 60 years ago Aristides Leao coined the term spreading depression (SD) to describe a transient "depression" of electrocorticographic activity that lasts up to several minutes and slowly "spreads" in all directions in cortex by way of gray matter contiguity.1 Today we know that SD is an intrinsic electrophysiological property of central nervous systems, evolutionarily preserved from locust to man. Largely based on the similarities between the symptomatology of migraine aura and the electrophysiological features of SD, a causal relationship between the two has long been hypothesized. 8-10 Recently, the SD theory of migraine gained momentum by evidence emerging from both clinical and experimental studies despite being challenged by alternative mechanisms and hypotheses. Here, I will review the accumulated evidence supporting a causal relationship between SD and migraine aura and headache, and discuss the contested notion that SD may also be involved in migraine attacks without a "perceived" aura. C1 [Ayata, Cenk] Harvard Univ, Sch Med, Dept Radiol, Neurovasc Res Lab, Boston, MA 02115 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Stroke Serv, Dept Neurol,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Ayata, C (reprint author), 149 13th St,Room 6408, Charlestown, MA 02129 USA. FU NIH [NS061505] FX This work was supported in part by NIH (NS061505). NR 63 TC 72 Z9 74 U1 2 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-8748 J9 HEADACHE JI Headache PD APR PY 2010 VL 50 IS 4 BP 725 EP 730 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 577TH UT WOS:000276246400027 PM 20456160 ER PT J AU DesRoches, CM Campbell, EG Vogeli, C Zheng, J Rao, SR Shields, AE Donelan, K Rosenbaum, S Bristol, SJ Jha, AK AF DesRoches, Catherine M. Campbell, Eric G. Vogeli, Christine Zheng, Jie Rao, Sowmya R. Shields, Alexandra E. Donelan, Karen Rosenbaum, Sara Bristol, Steffanie J. Jha, Ashish K. TI Electronic Health Records' Limited Successes Suggest More Targeted Uses SO HEALTH AFFAIRS LA English DT Article ID PHYSICIAN ORDER ENTRY; QUALITY-OF-CARE; INFORMATION-TECHNOLOGY; HOSPITAL COSTS; INTERVENTION; PERFORMANCE; EFFICIENCY; REDUNDANT; BENEFITS; SYSTEMS AB Understanding whether electronic health records, as currently adopted, improve quality and efficiency has important implications for how best to employ the estimated $20 billion in health information technology incentives authorized by the American Recovery and Reinvestment Act of 2009. We examined electronic health record adoption in U. S. hospitals and the relationship to quality and efficiency. Across a large number of metrics examined, the relationships were modest at best and generally lacked statistical or clinical significance. However, the presence of clinical decision support was associated with small quality gains. Our findings suggest that to drive substantial gains in quality and efficiency, simply adopting electronic health records is likely to be insufficient. Instead, policies are needed that encourage the use of electronic health records in ways that will lead to improvements in care. C1 [DesRoches, Catherine M.; Campbell, Eric G.; Vogeli, Christine; Donelan, Karen] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Bristol, Steffanie J.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Rosenbaum, Sara] George Washington Univ, Dept Hlth Policy, Sch Publ Hlth & Hlth Serv, Washington, DC USA. RP DesRoches, CM (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. EM cdesroches@partners.org FU Office of the National Coordinator for Health Information Technology; Robert Wood Johnson Foundation FX Quality data in this paper were presented at the AcademyHealth Annual Research Meeting in Chicago, Illinois, June 2009. Financial support for this research was provided by the Office of the National Coordinator for Health Information Technology and the Robert Wood Johnson Foundation. Ashish Jha receives consulting fees from UptoDate. Catherine DesRoches and Eric Campbell receive consulting fees from Abt Associates. The authors thank Paola Miralles for assistance in the preparation of this paper. NR 22 TC 83 Z9 83 U1 0 U2 8 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD APR PY 2010 VL 29 IS 4 BP 639 EP 646 DI 10.1377/hlthaff.2009.1086 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 579HS UT WOS:000276360200011 PM 20368593 ER PT J AU Singer, SJ Rosen, A Zhao, SB Ciavarelli, AP Gaba, DM AF Singer, Sara J. Rosen, Amy Zhao, Shibei Ciavarelli, Anthony P. Gaba, David M. TI Comparing safety climate in naval aviation and hospitals: Implications for improving patient safety SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article DE aviation; hospitals; industry comparison; safety climate; safety culture; survey research ID HEALTH-CARE ORGANIZATIONS; HIGH-RELIABILITY; CULTURE; MANAGEMENT; ERROR; PERFORMANCE; VALIDATION; INDUSTRIES; LESSONS; MISHAPS AB Background: Evidence of variation in safety climate suggests the need for improvement among at least some hospitals. However, comparisons only among hospitals may underestimate the improvement required. Comparison of hospitals with analogous industries may provide a broader perspective on the safety status of our nation's hospitals. Purpose: The purpose of this study was to compare safety climate among hospital workers with personnel from naval aviation, an organization that operates with high reliability despite intrinsically hazardous conditions. Methodology: We surveyed a random sample of health care workers in 67 U. S. hospitals and, for generalizability, 30 veterans affairs hospitals using questions comparable with those posed at approximately the same time (2007) to a census of personnel from 35 squadrons of U. S. naval aviators. We received 13,841 (41%) completed surveys in U. S. hospitals, 5,511 (50%) in veterans affairs hospitals, and 14,854 (82%) among naval aviators. We examined differences in respondents' perceptions of safety climate at their institution overall and for 16 individual items. Findings: Safety climate was three times better on average among naval aviators than among hospital personnel. Naval aviators perceived a safer climate (up to seven times safer) than hospital personnel with respect to each of the 16 survey items. Compared with hospital managers, naval commanders perceived climate more like frontline personnel did. When contrasting naval aviators with hospital personnel working in comparably hazardous areas, safety climate discrepancies increased rather than decreased. One individual hospital performed as well as naval aviation on average, and at least one hospital outperformed the Navy benchmark for all but three individual survey items. C1 [Singer, Sara J.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. [Singer, Sara J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA USA. [Singer, Sara J.] Stanford Univ, Ctr Hlth Policy, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Rosen, Amy] VA Boston Healthcare Syst, Boston, MA USA. [Rosen, Amy] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Bedford, MA USA. [Zhao, Shibei] Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Ciavarelli, Anthony P.] Human Factors Associates Inc, Salinas, CA USA. [Gaba, David M.] Stanford Univ, Palo Alto, CA 94304 USA. [Gaba, David M.] VA Palo Alto Hlth Care Syst, Patient Safety Culture Inst, Palo Alto, CA USA. RP Singer, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. EM ssinger@hsph.harvard.edu FU AHRQ HHS [R01 HS013920] NR 44 TC 18 Z9 18 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-6274 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD APR-JUN PY 2010 VL 35 IS 2 BP 134 EP 146 DI 10.1097/HMR.0b013e3181c8b20c PG 13 WC Health Policy & Services SC Health Care Sciences & Services GA 581XB UT WOS:000276557800005 PM 20234220 ER PT J AU Selim, AJ Berlowitz, D Kazis, LE Rogers, W Wright, SM Qian, SX Rothendler, JA Spiro, A Miller, D Selim, BJ Fincke, BG AF Selim, Alfredo J. Berlowitz, Dan Kazis, Lewis E. Rogers, William Wright, Steven M. Qian, Shirley X. Rothendler, James A. Spiro, Avron, III Miller, Donald Selim, Bernardo J. Fincke, Benjamin G. TI Comparison of Health Outcomes for Male Seniors in the Veterans Health Administration and Medicare Advantage Plans SO HEALTH SERVICES RESEARCH LA English DT Article DE Health outcomes; system comparison; quality of care ID QUALITY-OF-CARE; MANAGED CARE; MYOCARDIAL-INFARCTION; ILL PATIENTS; MORTALITY; SERVICES; PROGRAM; SYSTEM; HOSPITALS; INDICATOR AB Objectives To compare the Veterans Health Administration (VHA) with the Medicare Advantage (MA) plans with regard to health outcomes. Data Sources The Medicare Health Outcome Survey, the 1999 Large Health Survey of Veteran Enrollees, and the Ambulatory Care Survey of Healthcare Experiences of Patients (Fiscal Years 2002 and 2003). Study Design A retrospective study. Extraction Methods Men 65+ receiving care in MA (N=198,421) or in VHA (N=360,316). We compared the risk-adjusted probability of being alive with the same or better physical (PCS) and mental (MCS) health at 2-years follow-up. We computed hazard ratio (HR) for 2-year mortality. Principal Findings Veterans had a higher adjusted probability of being alive with the same or better PCS compared with MA participants (VHA 69.2 versus MA 63.6 percent, p <.001). VHA patients had a higher adjusted probability than MA patients of being alive with the same or better MCS (76.1 versus 69.6 percent, p <.001). The HRs for mortality in the MA were higher than in the VHA (HR, 1.26 [95 percent CI 1.23-1.29]). Conclusions Our findings indicate that the VHA has better patient outcomes than the private managed care plans in Medicare. The VHA's performance offers encouragement that the public sector can both finance and provide exemplary health care. C1 [Selim, Alfredo J.] Edith Nourse Rogers Mem Hosp 152, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Selim, Alfredo J.] Boston VA Hlth Care Syst, Emergency Serv, W Roxbury, MA USA. [Selim, Alfredo J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Fincke, Benjamin G.] Edith Nourse Rogers Mem Hosp, Ctr Hlth Qual Outcomes & Econ Res, Dept Vet Affairs Med Ctr, Patient Care Serv,Med Serv, Bedford, MA USA. [Rothendler, James A.; Spiro, Avron, III; Miller, Donald] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Rogers, William] Tufts Univ New England Med Ctr, New England Med Ctr, Hlth Inst, Boston, MA USA. [Wright, Steven M.] US Dept Vet Affairs, Off Qual & Performance, Washington, DC USA. [Selim, Bernardo J.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Fincke, Benjamin G.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Selim, AJ (reprint author), Edith Nourse Rogers Mem Hosp 152, Ctr Hlth Qual Outcomes & Econ Res, Bldg 70,200 Springs Rd, Bedford, MA 01730 USA. EM alfredo.selim2@va.gov OI Spiro III, Avron/0000-0003-4080-8621; Kazis, Lewis/0000-0003-1800-5849 FU Centers for Medicare and Medicaid Services; National Committee for Quality Assurance (NCQA) [500-00-0055]; Office of Quality and Performance (OQP) of the Department of Veterans Affairs; Center for Health Quality, Outcomes and Economic Research (CHQOER); Department of Veterans Affairs; Boston University School of Public Health FX Disclosures: The research in this article was supported by the Centers for Medicare and Medicaid Services and the National Committee for Quality Assurance (NCQA) under contract numbers 500-00-0055 with NCQA, Office of Quality and Performance (OQP) of the Department of Veterans Affairs, The Center for Health Quality, Outcomes and Economic Research (CHQOER), Department of Veterans Affairs and Boston University School of Public Health. NR 48 TC 11 Z9 11 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2010 VL 45 IS 2 BP 376 EP 396 DI 10.1111/j.1475-6773.2009.01068.x PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 565YT UT WOS:000275335900003 PM 20050934 ER PT J AU Parker, VA Clark, JA Leyson, J Calhoun, E Carroll, JK Freund, KM Battaglia, TA AF Parker, Victoria A. Clark, Jack A. Leyson, Jenniffer Calhoun, Elizabeth Carroll, Jennifer K. Freund, Karen M. Battaglia, Tracy A. TI Patient Navigation: Development of a Protocol for Describing What Navigators Do SO HEALTH SERVICES RESEARCH LA English DT Article DE Continuity of patient care; social support; health services needs and demands; case management; patient navigation ID BREAST-CANCER; FOLLOW-UP; HEALTH DISPARITIES; URBAN-POPULATION; DIAGNOSIS; NETWORK; PREVENTION; PROGRAM; TRIAL; CARE AB Objective To develop a structured protocol for observing patient navigators at work, describing and characterizing specific activities related to their goals. Data Sources/Setting Fourteen extended observations of navigators at three programs within a national trial of patient navigation. Study Design Preliminary observations were guided by a conceptual model derived from the literature and expert consensus, then coded to develop and refine observation categories. These findings were then used to develop the protocol. Methods Observation fieldnotes were coded, using both a priori codes and new codes based on emergent themes. Using these codes, the team refined the model and constructed an observation tool that enables consistent categorization of the observed range of navigator actions. Findings Navigator actions across a wide variety of settings can be categorized in a matrix with two dimensions. One dimension categorizes the individuals and organizational entities with whom the navigator interacts; the other characterizes the types of tasks carried out by the navigators in support of their patients. Conclusions Use of this protocol will enable researchers to systematically characterize and compare navigator activities within and across programs. C1 [Parker, Victoria A.; Clark, Jack A.; Leyson, Jenniffer] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02118 USA. [Parker, Victoria A.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Clark, Jack A.] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res VA HSR&D, Bedford, MA USA. [Calhoun, Elizabeth] Univ Illinois, Sch Publ Hlth, Div Hlth Policy & Adm, Chicago, IL USA. [Carroll, Jennifer K.] Univ Rochester, Med Ctr, Dept Family Med & Oncol, Family Med Res Programs, Rochester, NY 14642 USA. [Freund, Karen M.; Battaglia, Tracy A.] Boston Univ, Sch Med, Dept Med, Womens Hlth Unit,Sect Gen Internal Med, Boston, MA 02118 USA. [Freund, Karen M.; Battaglia, Tracy A.] Boston Univ, Sch Med, Womens Hlth Interdisciplinary Res Ctr, Boston, MA 02118 USA. RP Parker, VA (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 715 Albany St T3W, Boston, MA 02118 USA. EM vaparker@bu.edu OI Clark, Jack/0000-0002-7424-1670; Parker, Victoria/0000-0002-7632-9174; Battaglia, Tracy/0000-0001-8475-1212; Freund, Karen/0000-0002-9049-5574 FU Avon Foundation; University of Rochester Medical Center FX Joint Acknowledgment/Disclosure Statement: The research reported in this paper was supported by a grant from the Avon Foundation to Boston Medical Center (BMC), which subcontracted with the research teams at University of Chicago (Chicago) and University of Rochester Medical Center (Rochester). Battaglia is principal investigator of the project. Parker is co-principal investigator; Clark, co-investigator; Freund, clinical consultant; and Leyson, research assistant. All authors except Parker are also principal investigators, co-principal investigators, or research staff at their respective participating sites in the National Cancer Institute's Patient Navigation Research Project (PNRP). NR 25 TC 26 Z9 27 U1 2 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2010 VL 45 IS 2 BP 514 EP 531 DI 10.1111/j.1475-6773.2009.01079.x PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 565YT UT WOS:000275335900010 PM 20132342 ER PT J AU Ferencik, M AF Ferencik, Maros TI Assessment of coronary plaque burden by computed tomography: getting closer-step by step SO HEART LA English DT Editorial Material ID LIPID-LOWERING THERAPY; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUE; PROGNOSTIC VALUE; ANGIOGRAPHY; TRIAL C1 [Ferencik, Maros] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ferencik, Maros] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ferencik, M (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Gray Bigelow Bldg 8-804, Boston, MA 02114 USA. EM maros_ferencik@hms.harvard.edu NR 18 TC 2 Z9 3 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD APR PY 2010 VL 96 IS 8 BP 575 EP 576 DI 10.1136/hrt.2009.187815 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 577CH UT WOS:000276198000001 PM 20357384 ER PT J AU Mansour, M Forleo, GB Pappalardo, A Barrett, C Heist, EK Avella, A Bencardino, G Dello Russo, A Casella, M Ruskin, JN Tondo, C AF Mansour, Moussa Forleo, Giovanni B. Pappalardo, Augusto Barrett, Conor Heist, E. Kevin Avella, Andrea Bencardino, Gianluigi Dello Russo, Antonio Casella, Michela Ruskin, Jeremy N. Tondo, Claudio TI Combined use of cryoballoon and focal open-irrigation radiofrequency ablation for treatment of persistent atrial fibrillation: Results from a pilot study SO HEART RHYTHM LA English DT Article DE Atrial fibrillation; Balloon catheter; Catheter ablation; Cryoablation; Pulmonary vein isolation ID PULMONARY VEIN ISOLATION; TERM-FOLLOW-UP; CATHETER ABLATION; BALLOON CATHETER; INITIAL-EXPERIENCE; END-POINT; CRYOABLATION; SYSTEM; SUBSTRATE; EFFICACY AB BACKGROUND Pulmonary vein isolation (PVI) achieved using a cryoballoon has been shown to be safe and effective. This treatment modality has limited effectiveness for treatment of persistent atrial fibrillation (AF). OBJECTIVE The purpose of this study was to evaluate a combined approach using a cryoballoon for treatment of PVI and focal radiofrequency (RF) left atrial substrate ablation for treatment of persistent AF. METHODS Twenty-two consecutive patients with persistent AF were included in the study. PVI initially was performed with a cryoballoon. Left atrial complex fractionated atrial electrograms (CFAEs) then were ablated using an RF catheter. Finally, linear ablations using the RF catheter were performed. RESULTS Eighty-three PVs, including five with left common ostia, were targeted and isolated (100%). Seventy-seven (94%) of 82 PVs targeted with the cryoballoon were isolated, and 5 (6%) required use of RF energy to complete isolation. A mean of 9.7 +/- 2.6 cryoablation applications per patient was needed to achieve PVI. Median time required for cryoablation per vein was 600 seconds, and mean number of balloon applications per vein was 2.5 +/- 1.0. In 19 (86%) patients in whom AF persisted after PVI, CFAE areas were ablated using the RF catheter. Two cases of transient phrenic nerve paralysis occurred. After a single procedure and mean follow-up of 6.0 +/- 2.9 months, 86.4% of patients were AF-free without antiarrhythmic drugs. CONCLUSION A combined approach of cryoablation and RF ablation for treatment of persistent AF is feasible and is associated with a favorable short-term outcome. C1 [Mansour, Moussa; Forleo, Giovanni B.; Pappalardo, Augusto; Avella, Andrea; Bencardino, Gianluigi; Dello Russo, Antonio; Casella, Michela; Tondo, Claudio] Univ Cattolica Sacro Cuore, St Camillo Forlanini Hosp, Cardiac Arrhythmia & Heart Failure Res Inst, I-00151 Rome, Italy. [Mansour, Moussa; Barrett, Conor; Heist, E. Kevin; Ruskin, Jeremy N.; Tondo, Claudio] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. RP Tondo, C (reprint author), Univ Cattolica Sacro Cuore, St Camillo Forlanini Hosp, Cardiac Arrhythmia & Heart Failure Res Inst, Piazza Carlo Forlanini 1, I-00151 Rome, Italy. EM c.tondo@libero.it RI Forleo, Giovanni/G-8788-2012 FU St. Jude Medical FX Dr. Mansour has served as a consultant for Bard EP, Medtronic, St. Jude Medical, and Biosense Webster. Dr. Heist has received research support from St. Jude Medical. Dr. Ruskin serves as a consultant to Medtronic and Biosense Webster, a Scientific Steering Committee member for CryoCath, and a Clinical Oversight Committee member for CardioFocus, and has served as a speaker at St. Jude Medical and Boston Scientific Fellows' Educational Programs. Dr. Tondo has served as a member of the advisory board of Biosense Webster, and has been as a consultant for, and received lecture fees from, St. Jude Medical. NR 34 TC 14 Z9 14 U1 0 U2 2 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 APR PY 2010 VL 7 IS 4 BP 452 EP 458 DI 10.1016/j.hrthm.2009.12.012 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 576ZV UT WOS:000276190000004 PM 20188229 ER PT J AU Larobina, ME AF Larobina, Marco E. TI The Role of Surgical Ventricular Remodelling in Ischemic Cardiomyopathy: Implications of the Results of the STICH Trial SO HEART SURGERY FORUM LA English DT Article ID CHRONIC HEART-FAILURE; MYOCARDIUM; BYPASS; SURGERY C1 Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02115 USA. RP Larobina, ME (reprint author), Massachusetts Gen Hosp, Dept Cardiac Surg, 55 Fruit St, Boston, MA 02115 USA. EM marcolarobina@hotmail.com NR 14 TC 0 Z9 0 U1 0 U2 1 PU FORUM MULTIMEDIA PUBLISHING, LLC PI CHARLOTTESVILLE PA 375 GREENBRIER DR, CHARLOTTESVILLE, VA 22901 USA SN 1098-3511 J9 HEART SURG FORUM JI Heart Surg. Forum PD APR PY 2010 VL 13 IS 2 BP E101 EP E104 DI 10.1532/HSF98.20091152 PG 4 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 605MS UT WOS:000278352300008 PM 20444672 ER PT J AU Bejar, R Ebert, BL AF Bejar, Rafael Ebert, Benjamin L. TI The Genetic Basis of Myelodysplastic Syndromes SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Myelodysplastic syndromes; Genetic mutations; Myeloid neoplasms; Karyotypic abnormalities ID ACUTE MYELOID-LEUKEMIA; THERAPY-RELATED MYELODYSPLASIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; AML1/RUNX1 POINT MUTATIONS; FAMILIAL PLATELET DISORDER; ACUTE MYELOGENOUS LEUKEMIA; COMMONLY DELETED SEGMENT; CHROMOSOME 5Q DELETION; N-RAS MUTATIONS; UNIPARENTAL DISOMY AB Myelodysplastic syndrome (MDS) disorders are clonal diseases that often carry stereotypic chromosomal abnormalities. A smaller proportion of cases harbor point mutations that activate oncogenes or inactivate tumor suppressor genes. New technologies have accelerated the pace of discovery and are responsible for the identification of novel genetic mutations associated with MDS and other myeloid neoplasms. These discoveries have identified novel mechanisms in the pathogenesis of MDS. This article touches on the better known genetic abnormalities in MDS and explains in greater detail those that have been discovered more recently. Understanding how mutations lead to MDS and how they might cooperate with each other has become more complicated as the number of MDS-associated genetic abnormalities has grown. In some cases, these mutations have prognostic significance that could improve upon the various prognostic scoring systems in common clinical use. C1 [Bejar, Rafael; Ebert, Benjamin L.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Bejar, Rafael; Ebert, Benjamin L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ebert, Benjamin L.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Ebert, BL (reprint author), Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Karp Res Bldg,CHRB 05-211,1 Blackfan Circle, Boston, MA 02115 USA. EM Benjamin_Ebert@dfci.harvard.edu FU NCI NIH HHS [T32 CA009172] NR 126 TC 17 Z9 18 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2010 VL 24 IS 2 BP 295 EP + DI 10.1016/j.hoc.2010.02.001 PG 22 WC Oncology; Hematology SC Oncology; Hematology GA 588BE UT WOS:000277040300003 PM 20359627 ER PT J AU Steensma, DP Stone, RM AF Steensma, David P. Stone, Richard M. TI Practical Recommendations for Hypomethylating Agent Therapy of Patients With Myelodysplastic Syndromes SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Myelodysplastic syndromes; Azacitidine; Decitabine; Hypomethylating agents; Drug therapy ID LEUKEMIA GROUP-B; ACUTE MYELOID-LEUKEMIA; QUALITY-OF-LIFE; PHASE-III; CONTROLLED TRIAL; DNA METHYLATION; ORAL MUCOSITIS; DOUBLE-BLIND; AZACITIDINE; CANCER AB Clinicians commonly administer one or the other of the two hypomethylating agents currently approved in the United States-azacitidine or decitabine to patients with aggressive forms of myelodysplastic syndromes (MDS). However, there continues to be uncertainty about the optimal choice of agent, the best initial dose and treatment schedule, the role of hypomethylating agents in patients with more indolent disease, the most appropriate management of treatment-associated adverse events, and the most desirable approach to maintain responses. The evidence base supporting clinical decisions around these questions varies widely in depth and quality. This article discusses practical considerations for clinicians who use hypomethylating agents to treat patients with MDS. C1 [Steensma, David P.; Stone, Richard M.] Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA. [Steensma, David P.; Stone, Richard M.] Harvard Univ, Sch Med, Boston, MA USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Dept Hematol Malignancies, 44 Binney St,Suite D1B30, Boston, MA 02115 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 NR 66 TC 12 Z9 14 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2010 VL 24 IS 2 BP 389 EP + DI 10.1016/j.hoc.2010.02.012 PG 19 WC Oncology; Hematology SC Oncology; Hematology GA 588BE UT WOS:000277040300009 PM 20359633 ER PT J AU Steensma, DP AF Steensma, David P. TI Novel Therapies for Myelodysplastic Syndromes SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Myelodysplastic syndromes; Histone deacetylase inhibitors; Clofarabine; Ezatiostat; Farnesyltransferase inhibitors; Laromustine ID ACUTE MYELOID-LEUKEMIA; HISTONE DEACETYLASE INHIBITORS; SULFONYLHYDRAZINE ALKYLATING AGENT; FARNESYL TRANSFERASE INHIBITOR; MULTICENTER DOSE-ESCALATION; GLUTATHIONE ANALOG PRODRUG; TRANS-RETINOIC ACID; VALPROIC ACID; CLORETAZINE VNP40101M; PHASE-II AB Preliminary therapeutic successes have prompted a new wave of clinical trials enrolling patients with myelodysplastic syndromes (MDS), using compounds with a broad range of potential mechanisms of action. This article discusses several of the agents currently in development for MDS, reviewing clinical trial data related to five classes of novel therapeutics: clofarabine, a halogenated purine nucleoside analog; ezatiostat (TLK199), a glutathione analog that indirectly activates c-Jun kinase; tipifarnib, a farnesyltransferase inhibitor; laromustine (cloretazine), an alkylating agent with a metabolite that inhibits one mechanism of DNA damage repair; and eight drugs that inhibit histone deacetylase. Although MDS are still difficult clinical problems, and most patients with MDS still succumb to disease-related complications within 3 to 5 years of diagnosis, ongoing development of novel agents promises that there will be new treatment options for patients within the next 5 to 10 years. C1 Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Dept Hematol Malignancies, 44 Binney St,Suite D1B30, Boston, MA 02115 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 NR 63 TC 9 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2010 VL 24 IS 2 BP 423 EP + DI 10.1016/j.hoc.2010.02.010 PG 21 WC Oncology; Hematology SC Oncology; Hematology GA 588BE UT WOS:000277040300011 PM 20359635 ER PT J AU Cutler, C AF Cutler, Corey TI Patient Selection for Transplantation in the Myelodysplastic Syndromes SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Stem cell transplantation; Myelodysplastic syndromes; Allogeneic ID STEM-CELL TRANSPLANTATION; COMORBIDITY INDEX; PROGNOSTIC IMPACT; UNRELATED DONORS; RISK; SURVIVAL; MDS; INTENSITY; RELEVANCE; LEUKEMIA AB Allogeneic hematopoietic stem cell transplantation remains the only known curative procedure for the myelodysplastic syndromes (MDS). Because the median age at diagnosis for MDS is in the late seventh decade of life, despite the curative potential, transplantation is not undertaken routinely, and careful consideration must be made regarding the appropriateness of the transplant recipient. This article focuses on appropriate patient selection for transplantation for MDS. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cutler, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,D1B13, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu NR 21 TC 4 Z9 5 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2010 VL 24 IS 2 BP 469 EP + DI 10.1016/j.hoc.2010.02.006 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 588BE UT WOS:000277040300014 PM 20359638 ER PT J AU Benoit, MM Raij, T Lin, FH Jaaskelainen, IP Stufflebeam, S AF Benoit, Margo McKenna Raij, Tommi Lin, Fa-Hsuan Jaaskelainen, Iiro P. Stufflebeam, Steven TI Primary and Multisensory Cortical Activity is Correlated with Audiovisual Percepts SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; speech perception; auditory cortex; visual cortex; hearing; cochlear implant ID AUDITORY-VISUAL INTEGRATION; LATERAL OCCIPITAL COMPLEX; SUPERIOR TEMPORAL SULCUS; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; SPEECH-PERCEPTION; HUMAN BRAIN; SELECTIVE ADAPTATION; CROSSMODAL BINDING; COCHLEAR IMPLANTS AB Incongruent auditory and visual stimuli can elicit audiovisual illusions such as the McGurk effect where visual /ka/ and auditory /pa/ fuse into another percept such as/ta/. In the present study, human brain activity was measured with adaptation functional magnetic resonance imaging to investigate which brain areas support such audiovisual illusions. Subjects viewed trains of four movies beginning with three congruent /pa/ stimuli to induce adaptation. The fourth stimulus could be (i) another congruent /pa/, (ii) a congruent /ka/, (hi) an incongruent stimulus that evokes the McGurk effect in susceptible individuals (lips /ka/ voice /pa/), or (iv) the converse combination that does not cause the McGurk effect (lips /pa/ voice/ ka/). This paradigm was predicted to show increased release from adaptation (i.e. stronger brain activation) when the fourth movie and the related percept was increasingly different from the three previous movies. A stimulus change in either the auditory or the visual stimulus from /pa/ to /ka/ (iii, iv) produced within-modality and cross-modal responses in primary auditory and visual areas. A greater release from adaptation was observed for incongruent non-McGurk (iv) compared to incongruent McGurk (iii) trials. A network including the primary auditory and visual cortices, nonprimary auditory cortex, and several multisensory areas (superior temporal sulcus, intraparietal sulcus, insula, and pre-central cortex) showed a correlation between perceiving the McGurk effect and the fMRI signal, suggesting that these areas support the audiovisual illusion. Hum Brain Mapp 31:526-538, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Benoit, Margo McKenna] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. [Benoit, Margo McKenna; Raij, Tommi; Lin, Fa-Hsuan; Jaaskelainen, Iiro P.; Stufflebeam, Steven] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. [Jaaskelainen, Iiro P.] Helsinki Univ Technol, Lab Computat Engn, FIN-02150 Espoo, Finland. [Stufflebeam, Steven] Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol HST, Cambridge, MA 02139 USA. RP Benoit, MM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM margo@nmr.mgh.harvard.edu RI Imhof, Margarete/F-8471-2011; Jaaskelainen, Iiro/C-7392-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950 FU Otolaryngology Research Training Grant (MEEI) [T32 DC000020-18]; NIH [R01 NS048279-01A1]; Finnish Cultural Foundation [K08 MH067966, 5P41RR14075]; MIND Institute; Academy of Finland; Sigrid Juselius Foundation FX Contract grant sponsor: Otolaryngology Research Training Grant (MEEI); Contract grant number: T32 DC000020-18; Contract grant sponsor: NIH; Contract grant number: R01 NS048279-01A1; Contract grant sponsor: The Finnish Cultural Foundation; Contract grant numbers: K08 MH067966, 5P41RR14075; Contract grant sponsors: The MIND Institute, The Academy of Finland, The Sigrid Juselius Foundation. NR 90 TC 34 Z9 34 U1 4 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD APR PY 2010 VL 31 IS 4 BP 526 EP 538 DI 10.1002/hbm.20884 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 581PZ UT WOS:000276537800003 PM 19780040 ER PT J AU Miura, K Miura, S Yoshiura, K Seminara, S Hamaguchi, D Niikawa, N Masuzaki, H AF Miura, Kiyonori Miura, Shoko Yoshiura, Koh-ichiro Seminara, Stephanie Hamaguchi, Daisuke Niikawa, Norio Masuzaki, Hideaki TI A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1 SO HUMAN REPRODUCTION LA English DT Article DE Kallmann syndrome; FGFR1b mutation; fibroblast growth factor receptor 1 isoform expression ID OF-FUNCTION MUTATIONS; HYPOGONADOTROPIC HYPOGONADISM; FGFR1; GENE; DEFICIENCY; PHENOTYPES; MOLECULES; ADHESION AB Fibroblast growth factor receptor 1 (FGFR1) is one of the causative genes for Kallmann syndrome (KS), which is characterized by isolated hypogonadotropic hypogonadism with anosmia/hyposmia. The third immunoglobulin-like domain (D3) of FGFR1 has the isoforms FGFR1-IIIb and FGFR1-IIIc, which are generated by alternative splicing of exons 8A and 8B, respectively. To date, the only mutations to have been identified in D3 of FGFR1 are in exon 8B. We performed mutation analysis of FGFR1 in a 23-year-old female patient with KS and found a missense mutation (c.1072C > T) in exon 8A of FGFR1. The c.1072C > T mutation was not detected in her family members or in 220 normal Japanese and 100 Caucasian female controls. No mutation in other KS genes, KS 1, prokineticin-2, prokineticin receptor-2 and FGF-8 was detected in the affected patient or in her family members. Therefore, this is the first case of KS carrying a de novo missense mutation in FGFR1 exon 8A, suggesting that isoform FGFR1-IIIb, as well as isoform FGFR1-IIIc, plays a crucial role in the pathogenesis of KS. C1 [Miura, Kiyonori; Miura, Shoko; Hamaguchi, Daisuke; Masuzaki, Hideaki] Nagasaki Univ, Grad Sch Biomed Sci, Dept Obstet & Gynecol, Nagasaki 852, Japan. [Yoshiura, Koh-ichiro] Nagasaki Univ, Grad Sch Biomed Sci, Dept Human Genet, Nagasaki 852, Japan. [Seminara, Stephanie] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Niikawa, Norio] Hokkaido Univ, Res Inst Personalized Hlth Sci, Sapporo, Hokkaido 060, Japan. RP Miura, K (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Dept Obstet & Gynecol, 1-7-1 Sakamoto, Nagasaki 852, Japan. EM kiyonori@nagasaki-u.ac.jp FU Science and Technology Agency (JST) [15-B09]; Naito Foundation, by Grant-in-Aid for Young Scientists; Ministry of Education, Sports, Culture, Science and Technology of Japan [21791567]; Ministry of Health, Labor and Welfare [20C-1]; Nagasaki University, Japan FX K. M. was supported, in part, by Seeds (No. 15-B09) from the Japan Science and Technology Agency (JST), by grants from the Naito Foundation, by Grant-in-Aid for Young Scientists (B) (no.21791567) from the Ministry of Education, Sports, Culture, Science and Technology of Japan, by a Grant for Child Health and Development (20C-1) from the Ministry of Health, Labor and Welfare, and by Grant-in-Aid for Scienti. c Research from Nagasaki University, Japan. NR 19 TC 2 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD APR PY 2010 VL 25 IS 4 BP 1076 EP 1080 DI 10.1093/humrep/deq006 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 572HH UT WOS:000275818200032 PM 20139426 ER PT J AU Sienko, KH Vichare, VV Balkwill, MD Wall, C AF Sienko, Kathleen H. Vichare, Vivek V. Balkwill, M. David Wall, Conrad, III TI Assessment of Vibrotactile Feedback on Postural Stability During Pseudorandom Multidirectional Platform Motion SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Balance; balance aid; frequency-domain analysis; postural control; stabilogram diffusion analysis (SDA); vibrotactile display ID BALANCE PROSTHESIS; VESTIBULAR DEFICITS; PERTURBATIONS; MODEL; SWAY; PERFORMANCE; SUPPORT AB This study uses frequency-domain techniques and stabilogram diffusion analysis (SDA) to investigate the effect of vibrotactile feedback during continuous multidirectional perturbations of a support platform. Eight subjects with vestibular deficits were subjected to two-axis pseudorandom surface platform motion while donning a multiaxis vibrotactile feedback device that mapped body tilt estimates onto their torsos via a 3-row by 16-column array of tactile vibrators (tactors). Four tactor display configurations with spatial resolutions ranging between 22.5. and 90., in addition to the tactors OFF configuration, were evaluated. Power spectral density functions of body sway in the anterior-posterior (A/P) and medial-lateral (M/L) directions, and transfer functions between platform motion and body sway, were computed at frequencies ranging from 0.0178 to 3.56 Hz. Cross-spectral analysis revealed that the A/P responses were not significantly driven by M/L inputs, and vice versa, thus supporting the notion of independent A/P and M/L postural control. Vibrotactile feedback significantly decreased A/P and M/L spectral power, decreased transfer function gains up to a frequency of 1.8 and 0.6 Hz in the A/P and M/L directions, respectively, and increased phase leads above 0.3 Hz. SDA showed significantly decreased transition time for both A/P and M/L tilts, and decreased transition displacement and short-term diffusion coefficients for A/P tilt. However, the spatial resolution of the tactor displays did not affect subjects' performance, thereby supporting the use of a lower spatial resolution display in future device designs. C1 [Sienko, Kathleen H.; Vichare, Vivek V.] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA. [Balkwill, M. David; Wall, Conrad, III] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Sienko, KH (reprint author), Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA. EM sienko@umich.edu; vvichare@umich.edu; dbalkwill@meei.harvard.edu; cwall@mit.edu FU National Institutes of Health [R01 DC6201] FX This work was supported by the National Institutes of Health (National Institute on Deafness and Other Communication Disorders R01 DC6201). NR 29 TC 24 Z9 24 U1 0 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD APR PY 2010 VL 57 IS 4 BP 944 EP 952 DI 10.1109/TBME.2009.2036833 PG 9 WC Engineering, Biomedical SC Engineering GA 574NY UT WOS:000275998200019 PM 19932987 ER PT J AU Angelone, LM Ahveninen, J Belliveau, JW Bonmassar, G AF Angelone, Leonardo M. Ahveninen, Jyrki Belliveau, John W. Bonmassar, Giorgio TI Analysis of the Role of Lead Resistivity in Specific Absorption Rate for Deep Brain Stimulator Leads at 3T MRI SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Head model; intracranial electrodes; safety; simulations ID TO-NOISE RATIO; PARKINSONS-DISEASE; BIRDCAGE COIL; HUMAN HEAD; NEUROSTIMULATION SYSTEMS; TEMPERATURE ELEVATION; METALLIC IMPLANTS; FIELD; SAFETY; SAR AB Magnetic resonance imaging (MRI) on patients with implanted deep brain stimulators (DBSs) can be hazardous because of the antenna-effect of leads exposed to the incident radio-frequency field. This study evaluated electromagnetic field and specific absorption rate (SAR) changes as a function of lead resistivity on an anatomically precise head model in a 3T system. The anatomical accuracy of our head model allowed for detailed modeling of the path of DBS leads between epidermis and the outer table. Our electromagnetic finite difference time domain (FDTD) analysis showed significant changes of 1 g and 10 g averaged SAR for the range of lead resistivity modeled, including highly conductive leads up to highly resistive leads. Antenna performance and whole-head SAR were sensitive to the presence of the DBS leads only within 10%, while changes of over one order of magnitude were observed for the peak 10 g averaged SAR, suggesting that local SAR values should be considered in DBS guidelines. With rho(lead) = rho(copper), and the MRI coil driven to produce a wholehead SAR without leads of 3.2 W/kg, the 1 g averaged SAR was 1080 W/kg and the 10 g averaged SAR 120 W/kg at the tip of the DBS lead. Conversely, in the control case without leads, the 1 g and 10 g averaged SAR were 0.5 W/kg and 0.6 W/kg, respectively, in the same location. The SAR at the tip of lead was similar with electrically homogeneous and electrically heterogeneous models. Our results showthat computational models can support the development of novel lead technology, properly balancing the requirements of SAR deposition at the tip of the lead and power dissipation of the system battery. C1 [Angelone, Leonardo M.] US FDA, Div Phys, Off Sci, Silver Spring, MD 20993 USA. [Angelone, Leonardo M.] US FDA, Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Ahveninen, Jyrki; Belliveau, John W.; Bonmassar, Giorgio] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. RP Angelone, LM (reprint author), US FDA, Div Phys, Off Sci, Silver Spring, MD 20993 USA. EM leonardo.an-gelone@fda.hhs.gov OI Angelone, Leonardo/0000-0002-1105-021X FU National Institute of Neurological Disorders And Stroke [R01 NS037462]; National Institute of Biomedical Imaging and Bioengineering [R01EB006385]; National Center for Research Resources (NCRR) [P41-RR14075]; MIND institute FX This work was supported in part by the National Institute of Neurological Disorders And Stroke (R01 NS037462), in part by the National Institute of Biomedical Imaging and Bioengineering (R01EB006385), in part by the National Center for Research Resources (NCRR) (P41-RR14075), and in part by the MIND institute. NR 54 TC 14 Z9 14 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 2010 VL 29 IS 4 BP 1029 EP 1038 DI 10.1109/TMI.2010.2040624 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 575TJ UT WOS:000276091000006 PM 20335090 ER PT J AU Kinnaird, AN Anstead, GM AF Kinnaird, A. N. Anstead, G. M. TI Hemorrhagic Cystitis and Possible Neurologic Disease from BK Virus Infection in a Patient with AIDS SO INFECTION LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; ACTIVE ANTIRETROVIRAL THERAPY; POLYOMAVIRUS INFECTION; RECIPIENTS; NEPHRITIS; CIDOFOVIR; SURVIVAL; DNA AB BK virus (BKV)-associated hemorrhagic cystitis occurs in bone marrow transplant recipients but is rare among other immunosuppressed patients. We present a rare case of BKV-associated hemorrhagic cystitis in a 48-year-old man with AIDS and previously diagnosed progressive multifocal leukoencephalopathy. C1 [Anstead, G. M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, Off Educ Programs, San Antonio, TX 78229 USA. [Anstead, G. M.] S Texas Vet Healthcare Syst, Div Infect Dis, Dept Med, San Antonio, TX USA. RP Kinnaird, AN (reprint author), 4903 Edgemoor Ln,Apt 802, Bethesda, MD 20814 USA. EM akinnairdmd@gmail.com NR 27 TC 9 Z9 9 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0300-8126 J9 INFECTION JI Infection PD APR PY 2010 VL 38 IS 2 BP 124 EP 127 DI 10.1007/s15010-009-9201-5 PG 4 WC Infectious Diseases SC Infectious Diseases GA 584VI UT WOS:000276781100008 PM 20198406 ER PT J AU Joos, B Rieder, P Fischer, M Kuster, H Rusert, P Trkola, A Pillai, SK Wong, JK Weber, R Gunthard, HF AF Joos, Beda Rieder, Philip Fischer, Marek Kuster, Herbert Rusert, Peter Trkola, Alexandra Pillai, Satish K. Wong, Joseph K. Weber, Rainer Guenthard, Huldrych F. TI Association between specific HIV-1 Env traits and virologic control in vivo SO INFECTION GENETICS AND EVOLUTION LA English DT Article; Proceedings Paper CT 14th International Bioinformatics Workshop on Virus Evolution and Molecular Epidemiology CY SEP 08-12, 2008 CL Cape Town, SOUTH AFRICA DE HIV-1; Envelope gp120; Evolution; Machine learning ID STRUCTURED TREATMENT INTERRUPTIONS; POTENT ANTIRETROVIRAL THERAPY; VIRUS TYPE-1 ENV; CHRONIC INFECTION; SET-POINT; IMMUNITY; RNA; REPLICATION; PREDICTION; RESPONSES AB HIV RNA levels are influenced by genetic characteristics of both the host and the virus Here we applied machine learning techniques to determine if plasma-derived HIV-1 amino acid sequences can be used to predict spontaneous virologic control We studied the relationship between HIV-1 env genotype and viral load in 20 chronically infected patients undergoing treatment interruptions (SSITT, Swiss-Spanish Intermittent Treatment Trial) and in 104 primary HIV infected (PHI) patients before antiretroviral therapy (cART) and where applicable also after treatment stop Extensive longitudinal sampling during the interruptions was performed in nine SSITT patients Sequences obtained from these nine patients during the first virus rebound were used as a training data set and revealed a strong genetic signature (accuracy 98 6% in cross-validation) associated with control of viremia at levels below 5000 copies/mL of viral RNA maintained for at least 2 months after the final cART stop The simple sequence pattern at gp120 positions 268E/358T was confirmed to be predictive of control in the clonal sequences originating from these patients during all subsequent rebounds Sequences from the remaining 11 SSITT patients with less frequent sampling and from the PHI patients were used for external validation High sensitivities (71-100%) and negative predictive values (80-100%) but low positive predictive values (12-40%) were achieved in the patient-wise analysis which was based on presence of the genetic pattern in all clones. These results suggest that presence of virus lacking the amino acid pattern 268E/358T is associated with VL >5000 at baseline of PHI and with low probability of spontaneous virologic control after treatment stop Conversely, however, presence of 268E/358T does not predict control of viremia. These residues in HIV gp120 might affect in vivo HIV-1 fitness either at the level of Env function or influence susceptibility to adaptive or innate immune response (C) 2009 Elsevier B V All rights reserved C1 [Joos, Beda; Rieder, Philip; Fischer, Marek; Kuster, Herbert; Weber, Rainer; Guenthard, Huldrych F.] Univ Zurich Hosp, Dept Med, Div Infect Dis & Hosp Epidemiol, CH-8091 Zurich, Switzerland. [Rusert, Peter; Trkola, Alexandra] Univ Zurich, Inst Med Virol, CH-8006 Zurich, Switzerland. [Pillai, Satish K.; Wong, Joseph K.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Joos, B (reprint author), Univ Zurich Hosp, Dept Med, Div Infect Dis & Hosp Epidemiol, Ramistr 100, CH-8091 Zurich, Switzerland. RI Joos, Beda/D-5547-2009; SHCS, only/G-4080-2011; Weber, Rainer/D-5175-2012; SHCS, all/G-4072-2011; gunthard, huldrych/F-1724-2011; Kuster, Herbert/A-3912-2013; Trkola, Alexandra/K-2115-2012; Infektiologie, USZ/A-6921-2011; SHCS, ch/G-4077-2011 OI Joos, Beda/0000-0002-3082-8875; gunthard, huldrych/0000-0002-1142-6723; Trkola, Alexandra/0000-0003-1013-876X; FU NIDA NIH HHS [K01 DA024654] NR 29 TC 1 Z9 1 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD APR PY 2010 VL 10 IS 3 SI SI BP 365 EP 372 DI 10.1016/j.meegid.2009.06.002 PG 8 WC Infectious Diseases SC Infectious Diseases GA 586UB UT WOS:000276937900003 PM 19524069 ER PT J AU Gupta, N Bostrom, AG Kirschner, BS Ferry, GD Gold, BD Cohen, SA Winter, HS Baldassano, RN Abramson, O Smith, T Heyman, MB AF Gupta, Neera Bostrom, Alan G. Kirschner, Barbara S. Ferry, George D. Gold, Benjamin D. Cohen, Stanley A. Winter, Harland S. Baldassano, Robert N. Abramson, Oren Smith, Terry Heyman, Melvin B. TI Incidence of Stricturing and Penetrating Complications of Crohn's Disease Diagnosed in Pediatric Patients SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE abscess; fistula; non-inflammatory disease; complicated disease; children; adolescence; outcomes; database; registry; inflammatory bowel disease ID INFLAMMATORY-BOWEL-DISEASE; NOD2/CARD15 GENOTYPE; NATURAL-HISTORY; CHILDREN; BEHAVIOR; ONSET; CLASSIFICATION; PROGRESSION; CHILDHOOD; LOCATION AB Background: The development of disease complications is poorly characterized in pediatric patients with Crohn's disease (CD). Methods: We retrospectively determined the cumulative incidence of stricturing and penetrating complications of CD prior to first surgery utilizing data from 989 consecutively enrolled CD patients (age (0-17 years at diagnosis) collected between January 2000 and November 2003 and stored in the Pediatric IBD Consortium Registry. Results: Mean age at diagnosis was 11.5 +/- 3.8 (standard deviation) years. Median follow-up time was 2.8 years. Prior to first surgery, the cumulative incidence of stricturing or penetrating complications was 27% at 5 years and 38% at 10 years from the diagnosis of inflammatory bowel disease. The cumulative incidence of complicated disease was lowest in isolated colonic disease (P = 0.009). Penetrating complications that followed stricturing complications prior to first surgery occurred within 2 years of stricturing complications (cumulative incidence was 13% at 2 years from diagnosis of stricturing disease). Stricturing complications that followed penetrating complications prior to first surgery occurred within 8 years of penetrating complications (cumulative incidence was 26% at 8 years from diagnosis of penetrating complications). Conclusions: Strictures, abscesses, and fistulas are common in pediatric CD. Earlier aggressive management may be indicated. Prospective study is required to identify genetic and serologic markers that predict a patient's risk for the development of complicated disease and to determine optimal treatment regimens. C1 [Gupta, Neera; Bostrom, Alan G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Gupta, Neera; Heyman, Melvin B.] Univ Calif San Francisco, Childrens Hosp, San Francisco, CA 94143 USA. [Kirschner, Barbara S.] Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA. [Ferry, George D.; Smith, Terry] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Gold, Benjamin D.; Cohen, Stanley A.] Emory Univ, Sch Med, Atlanta, GA USA. [Gold, Benjamin D.; Cohen, Stanley A.] Childrens Healthcare Atlanta, Childrens Ctr Digest Healthcare, Atlanta, GA USA. [Winter, Harland S.] MassGen Hosp Children, Boston, MA USA. [Baldassano, Robert N.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Abramson, Oren] Kaiser Permanente No Calif, Oakland, CA USA. RP Gupta, N (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 500 Parnassus Ave,MU 407E,Box 0136, San Francisco, CA 94143 USA. EM ng719@yahoo.com FU National Institutes of Health (NIH) [DK060617, DK53708, DK006544, DK007762, DK077734]; Children's Digestive Health and Nutrition Foundation/Crohn's and Colitis Foundation of America (CCFA); CCFA Career Development Award; NIH/NCRR UCSF-CTSI [UL1 RR024131] FX Supported in pan by National Institutes of Health (NIH) grants DK060617 (to M.B.H.), DK53708 (to B.D.G.). DK006544 (to B.D.G.). DK007762 (to M.B.H., N.G.), and DK077734 (to N.G.): Children's Digestive Health and Nutrition Foundation/Crohn's and Colitis Foundation of America (CCFA) Award for New Investigators (to N.G.); CCFA Career Development Award (to N.G.): NIH/NCRR UCSF-CTSI Grant No. UL1 RR024131: and the CCFA. NR 19 TC 25 Z9 25 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD APR PY 2010 VL 16 IS 4 BP 638 EP 644 DI 10.1002/ibd.21099 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 578WW UT WOS:000276328500019 PM 19760783 ER PT J AU Burns, SP Kaufman, RP Mack, CD Bulger, E AF Burns, Stephen P. Kaufman, Robert P. Mack, Christopher D. Bulger, Eileen TI Cost of spinal cord injuries caused by rollover automobile crashes SO INJURY PREVENTION LA English DT Article ID RISK AB Objective To determine the reduction in direct cost for treatment of spinal cord injuries (SCI) in belted occupants involved in rollover automobile crashes in the USA that would result if severe roof intrusion were eliminated. Methods Risk of SCI per rollover crash and by belted/unbelted status was calculated for roof intrusion magnitude categories using 1993-2006 National Automotive Sampling System Crashworthiness Data System (CDS) data. Direct costs of SCI based on neurological level and completeness of SCI were calculated using data from the National SCI Statistical Center. Results A reduction in rate of SCI for belted occupants with >15 cm roof intrusion to the rate seen for belted occupants with 8-15 cm roof intrusion would reduce the direct cost of SCI by approximately $97 million annually. Conclusion There would be substantial cost savings solely by a reduction in one uncommon type of injury, SCI, if severe roof intrusion were eliminated. C1 [Burns, Stephen P.] Univ Washington, VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv 128, Seattle, WA 98108 USA. [Burns, Stephen P.; Kaufman, Robert P.; Mack, Christopher D.; Bulger, Eileen] Univ Washington, Harborview Injury Prevent & Res Ctr, Seattle, WA 98108 USA. [Burns, Stephen P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98108 USA. [Bulger, Eileen] Univ Washington, Dept Surg, Seattle, WA 98108 USA. RP Burns, SP (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv 128, 1660 S Columbian Way, Seattle, WA 98108 USA. EM spburns@u.washington.edu FU NHTSA [DTNH22-05-H-11001]; Centers for Disease Control and Prevention (CDC) [R49 CCR002570-19]; National Institute on Disability and Rehabilitation Research (NIDRR) [H133N060033]; Veterans Affairs (VA) Puget Sound Health Care System FX Work was performed for the Crash Injury Research and Engineering Network (CIREN) project at the University of Washington/Harborview Injury Prevention and Research Center in cooperation with the US Department of Transportation/National Highway Traffic Safety Administration (NHTSA). Funding has been provided by NHTSA under Cooperative Agreement Number DTNH22-05-H-11001. Additional support has been provided by Grant No. R49 CCR002570-19 from the Centers for Disease Control and Prevention (CDC), Grant No. H133N060033 from the National Institute on Disability and Rehabilitation Research (NIDRR), and the Veterans Affairs (VA) Puget Sound Health Care System. Views expressed are those of the authors and do not necessarily represent the views of NHTSA, CDC, NIDRR or VA. Study design, data acquisition, analysis and interpretation, manuscript preparation and review were conducted independent of sponsoring organisations. NR 20 TC 4 Z9 4 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1353-8047 J9 INJURY PREV JI Inj. Prev. PD APR PY 2010 VL 16 IS 2 BP 74 EP 78 DI 10.1136/ip.2008.021097 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 577FW UT WOS:000276208800002 PM 20363811 ER PT J AU Mok-Lin, E Ehrlich, S Williams, PL Petrozza, J Wright, DL Calafat, AM Ye, X Hauser, R AF Mok-Lin, E. Ehrlich, S. Williams, P. L. Petrozza, J. Wright, D. L. Calafat, A. M. Ye, X. Hauser, R. TI Urinary bisphenol A concentrations and ovarian response among women undergoing IVF SO INTERNATIONAL JOURNAL OF ANDROLOGY LA English DT Article; Proceedings Paper CT 5th Copenhagen Workshop on Endocrine Disruptgers - Ubiquitous Endocrine Disrupters and Possible Human Health Effects CY MAY 20-22, 2009 CL Copenhagen, DENMARK DE bisphenol A; in vitro fertilization; human oestradiol; oocyte ID FOLLICLE-STIMULATING-HORMONE; GRANULOSA-CELLS; INVITRO FERTILIZATION; ESTRADIOL RESPONSE; GROWTH-FACTORS; EXPOSURE; FOLLICULOGENESIS; DIMETHACRYLATE; APOPTOSIS; ANIMALS AB P>Bisphenol A (BPA) is a synthetic chemical used in the manufacture of materials present in many common consumer products. In experimental animals, BPA caused oocyte aneuploidy and reduced production of oestradiol. In a prospective cohort study, we investigated the association between urinary BPA concentrations and ovarian response among women undergoing in vitro fertilization (IVF) at the Massachusetts General Hospital (MGH) Fertility Center. The geometric mean of two specific-gravity (SG) adjusted urinary BPA concentrations collected during each IVF cycle was used as the cycle-specific BPA exposure level. BPA concentrations were measured using online solid phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. Peak serum oestradiol was measured using the Elecsys Estradiol II immunoassay kit. Multivariable mixed effect models and Poisson regression models adjusting for correlation between multiple IVF cycles in the same woman were used to evaluate the association between urinary BPA concentrations and ovarian response, adjusting for age, BMI and day 3 follicle stimulating hormone (FSH) levels, a clinical measure of ovarian reserve. Urinary BPA concentrations were measured in 84 women (mean age 35.6 years) undergoing 112 IVF cycles; 23 women (27%) contributed more than one IVF cycle. BPA concentrations ranged from < 0.4 to 25.5 mu g/L (geometric mean 2.52 +/- SD 3.2); 15% of urine samples had concentrations < 0.4 mu g/L. Peak serum oestradiol levels correlated with the total number of oocytes retrieved per cycle (r = 0.65, p < 0.001). For each log unit increase in SG-BPA, there was an average decrease of 12% (95% CI: 4, 23%; p = 0.007) in the number of oocytes retrieved and an average decrease of 213 pg/ml (95% CI: -407, -20; p = 0.03) in peak oestradiol. BPA was detected in the urine of the majority of women undergoing IVF, and was inversely associated with number of oocytes retrieved and peak oestradiol levels. C1 [Mok-Lin, E.; Petrozza, J.; Wright, D. L.; Hauser, R.] Massachusetts Gen Hosp, Fertil Ctr, Boston, MA 02114 USA. [Ehrlich, S.; Hauser, R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth Environm & Occupat Med & Epide, Boston, MA 02115 USA. [Williams, P. L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Calafat, A. M.; Ye, X.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM rhauser@hsph.harvard.edu RI Ehrlich , Shelley/L-6991-2015 FU NIEHS NIH HHS [R01 ES009718, R01 ES009718-13]; NIOSH CDC HHS [R01 OH008578, OH008578] NR 41 TC 79 Z9 81 U1 1 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-6263 J9 INT J ANDROL JI Int. J. Androl. PD APR PY 2010 VL 33 IS 2 BP 385 EP 393 DI 10.1111/j.1365-2605.2009.01014.x PG 9 WC Andrology SC Endocrinology & Metabolism GA 569XO UT WOS:000275636400027 PM 20002217 ER PT J AU Fang, SC Cassidy, A Christiani, DC AF Fang, Shona C. Cassidy, Adrian Christiani, David C. TI A Systematic Review of Occupational Exposure to Particulate Matter and Cardiovascular Disease SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Review DE particles; air pollution; epidemiology; environmental health; ischemic heart disease; occupation; inflammation; heart rate variability; meta-analysis ID HEART-RATE-VARIABILITY; BOILERMAKER CONSTRUCTION WORKERS; CORONARY-ARTERY-DISEASE; SHORT-TERM EXPOSURE; AIR-POLLUTION; MYOCARDIAL-INFARCTION; PULMONARY INFLAMMATION; ULTRAFINE PARTICLES; VASCULAR FUNCTION; OXIDATIVE STRESS AB Exposure to ambient particulate air pollution is a recognized risk factor for cardiovascular disease; however the link between occupational particulate exposures and adverse cardiovascular events is less clear. We conducted a systematic review, including meta-analysis where appropriate, of the epidemiologic association between occupational exposure to particulate matter and cardiovascular disease. Out of 697 articles meeting our initial criteria, 37 articles published from January 1990 to April 2009 (12 mortality; 5 morbidity; and 20 intermediate cardiovascular endpoints) were included. Results suggest a possible association between occupational particulate exposures and ischemic heart disease (IHD) mortality as well as non-fatal myocardial infarction (MI), and stronger evidence of associations with heart rate variability and systemic inflammation, potential intermediates between occupational PM exposure and IHD. In meta-analysis of mortality studies, a significant increase in IHD was observed (meta-IRR = 1.16; 95% CI: 1.06-1.26), however these data were limited by lack of adequate control for smoking and other potential confounders. Further research is needed to better clarify the magnitude of the potential risk of the development and aggravation of IHD associated with short and long-term occupational particulate exposures and to clarify the clinical significance of acute and chronic changes in intermediate cardiovascular outcomes. C1 [Fang, Shona C.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Cassidy, Adrian] Epidemiol Unit, Bootle L20 7HS, England. [Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Fang, SC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM sfang@hsph.harvard.edu; cassidya@liv.ac.uk; dchris@hsph.harvard.edu FU NIEHS NIH HHS [R01 ES009860] NR 84 TC 46 Z9 47 U1 0 U2 21 PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD APR PY 2010 VL 7 IS 4 BP 1773 EP 1806 DI 10.3390/ijerph7041773 PG 34 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 589BN UT WOS:000277119600030 PM 20617059 ER PT J AU Gans, JS Counselman, EF AF Gans, Jerome S. Counselman, Eleanor F. TI Patient Selection for Psychodynamic Group Psychotherapy: Practical and Dynamic Considerations SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID GROUP-THERAPY; COUNTERTRANSFERENCE; GUIDELINES; SHAME AB Most group therapists rely on clinical interviews to screen prospective group members' suitability for long-term, open-ended, psychodynamically oriented group therapy. Faulty selection is detrimental to everyone involved and can even lead to the demise of the group. In order to avoid, or at least significantly limit, premature terminations or problematic mismatches between a patient and the rest of the group, pre-group screening needs to examine reality factors, resistance, ambivalence, and their interplay. Therapists need to be aware of counter transferential pressures that affect the screening process. The careful exploration of six specific areas during the clinical interview process increases the likelihood of optimal patient selection and participation. A selective literature review and clinical examples are provided. C1 [Gans, Jerome S.; Counselman, Eleanor F.] Massachusetts Gen Hosp, Wellesley, MA USA. [Gans, Jerome S.; Counselman, Eleanor F.] Harvard Univ, Sch Med, Wellesley, MA USA. RP Gans, JS (reprint author), 55 Cleveland Rd, Wellesley, MA 02481 USA. EM Jsgans@comcast.net NR 44 TC 5 Z9 5 U1 1 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD APR PY 2010 VL 60 IS 2 BP 197 EP 220 PG 24 WC Psychology, Clinical SC Psychology GA 574MV UT WOS:000275994700003 PM 20297881 ER PT J AU Ammenwerth, E Schnell-Inderst, P Siebert, U AF Ammenwerth, Elske Schnell-Inderst, Petra Siebert, Uwe TI Vision and challenges of Evidence-Based Health Informatics: A case study of a CPOE meta-analysis SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE CPOE; Order entry; Health informatics; Evaluation; Systematic review; Meta-analysis; Publication bias; Evidence-Based Health Informatics ID PHYSICIAN ORDER ENTRY; UNEXPECTED INCREASED MORTALITY; RANDOMIZED CONTROLLED-TRIALS; DECISION-SUPPORT-SYSTEMS; INTENSIVE-CARE-UNIT; MEDICAL INFORMATICS; PUBLICATION BIAS; IMPLEMENTATION; QUALITY; TECHNOLOGY AB Objective: To discuss, taking the example of a meta-analysis on computerized physician order entry (CPOE) systems, the special challenges of Evidence-Based Health Informatics, defined as the conscientious, explicit and judicious use of current best evidence when making decisions about introduction and operation of information technology in a given health care setting. Methods: We conducted a case study by performing a systematic review and meta-analysis of CPOE studies. We collected and discussed the challenges we addressed and how they could be overcome. Results: Challenges comprise the correct identification of published health informatics evaluation studies, the low reporting and study quality of studies, the problem of combining evidence from heterogeneous studies, and the problem of publication bias in health informatics. Conclusion: Based on our experiences while conducting the CPOE meta-analysis, we argue that we are still at the beginning of Evidence-Based Health Informatics. To overcome the discussed challenges, health informatics should strive for harmonized terminology, a study registry, reporting standards, financial or legal incentives for conducting studies, methods to combine evidence from quantitative and qualitative studies, and guidelines for conducting and publishing evaluation studies. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Ammenwerth, Elske] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Informat Syst & Hlth Technol Asses, Inst Hlth Informat Syst, A-6060 Hall In Tirol, Austria. [Schnell-Inderst, Petra] Univ Duisburg Essen, Inst Hlth Care Management, D-45127 Essen, Germany. [Schnell-Inderst, Petra; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Informat Syst & Hlth Technol Asses, Inst Publ Hlth Med Decis Making & Hlth Technol As, A-6060 Hall In Tirol, Austria. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Ammenwerth, E (reprint author), UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Informat Syst & Hlth Technol Asses, Inst Hlth Informat Syst, Eduard Wallnofer Zentrum 1, A-6060 Hall In Tirol, Austria. EM Elske.ammenwerth@umit.at RI Ammenwerth, Elske/F-5430-2010; OI Ammenwerth, Elske/0000-0002-3244-6918 NR 52 TC 9 Z9 10 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 J9 INT J MED INFORM JI Int. J. Med. Inform. PD APR PY 2010 VL 79 IS 4 BP E83 EP E88 DI 10.1016/j.ijmedinf.2008.11.003 PG 6 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 577AJ UT WOS:000276191600017 PM 19157969 ER PT J AU Choi, YK Wong, EHF Henry, B Shahid, M Tarazi, FI AF Choi, Yong Kee Wong, Erik H. F. Henry, Brian Shahid, Mohammed Tarazi, Frank I. TI Repeated effects of asenapine on adrenergic and cholinergic muscarinic receptors SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Adrenergic receptors; asenapine; frontal cortex; hippocampus; muscarinic receptors ID MEDIAL PREFRONTAL CORTEX; PSYCHOPHARMACOLOGICAL AGENT; RAT-BRAIN; SCHIZOPHRENIA; DOPAMINE; SUBTYPES; PHARMACOLOGY; 5-HT2A AB Adrenergic (alpha(1) and alpha(2)) and cholinergic muscarinic (M(1)-M(5)) receptor binding in rat forebrain was quantified after 4 wk of twice-daily subcutaneous administration of asenapine or vehicle. Asenapine (0.03, 0.1, and 0.3 mg/kg) produced increases in [(3)H]prazosin binding to alpha(1)-adrenergic receptors in the medial prefrontal cortex (mPFC: 30%, 39%, 57%) and dorsolateral frontal cortex (DFC: 27%, 37%, 53%,) and increased [(3)H]RX821002 binding to alpha(2)-adrenergic receptors in mPFC (36%, 43%, 50%) and DFC (41%, 44%, 52%). Despite showing no appreciable affinity for muscarinic receptors, asenapine produced regionally selective increases in binding of [(3)H]QNB to M(1)-M(5) receptors in mPFC (26%, 31%, 43%), DFC (27%, 34%, 41%), and hippocampal CA1 (40%, 44%, 42%) and CA3 (25%, 52%, 48%) regions. These regionally selective effects of asenapine on adrenergic and cholinergic muscarinic receptor subtypes may contribute to its beneficial clinical effects in the treatment of schizophrenia and bipolar disorder. C1 [Choi, Yong Kee; Tarazi, Frank I.] Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Belmont, MA USA. [Choi, Yong Kee; Tarazi, Frank I.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Choi, Yong Kee; Tarazi, Frank I.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Wong, Erik H. F.] AstraZeneca Pharmaceut LP, CNS Discovery, Wilmington, DE USA. [Henry, Brian] Schering Plough Corp, Translat Med Res Ctr, Singapore, Singapore. [Shahid, Mohammed] Schering Plough Corp, Newhouse, Lanark, Scotland. RP Tarazi, FI (reprint author), Harvard Univ, Sch Med, McLean Hosp, Lab Psychiat Neurosci, 115 Mill St, Belmont, MA 02478 USA. EM ftarazi@hms.harvard.edu FU Korean Government [KRF-2006-214-C00057]; Schering-Plough [HD-052752]; Pfizer Inc. FX Supported by Korea Research Foundation Grant funded by the Korean Government (KRF-2006-214-C00057) (Y.K.C.), HD-052752, Schering-Plough and Pfizer Inc. (F.I.T.). Editorial support was provided by Complete Healthcare Communications, Inc., and was funded by Schering-Plough. NR 29 TC 9 Z9 11 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD APR PY 2010 VL 13 IS 3 BP 405 EP 410 DI 10.1017/S1461145709990824 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 586RA UT WOS:000276928200013 PM 19835670 ER PT J AU Jones, D Roy, SC Avant, K AF Jones, Dorothy Roy, Sr Callista Avant, Kay TI Marjory Gordon PhD, RN, FAAN, Named American Academy Living Legend SO INTERNATIONAL JOURNAL OF NURSING TERMINOLOGIES AND CLASSIFICATIONS LA English DT Biographical-Item C1 [Jones, Dorothy; Roy, Sr Callista] Boston Coll, Connell Sch Nursing, Boston, MA USA. [Jones, Dorothy] Massachusetts Gen Hosp, Yvonne Munn Ctr Nursing Res, Boston, MA 02114 USA. [Avant, Kay] Univ Texas San Antonio, San Antonio, TX USA. RP Jones, D (reprint author), Boston Coll, Connell Sch Nursing, Boston, MA USA. EM Jones@bc.edu NR 1 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1541-5147 EI 1744-618X J9 INT J NURS TERMIN CL JI Int. J. Nurs. Terminol. Classif. PD APR-JUN PY 2010 VL 21 IS 2 BP 80 EP 81 DI 10.1111/j.1744-618X.2010.01149.x PG 2 WC Nursing SC Nursing GA V23EW UT WOS:000208327100005 PM 20500614 ER PT J AU Irlbeck, T Massaro, JM Bamberg, F O'Donnell, CJ Hoffmann, U Fox, CS AF Irlbeck, T. Massaro, J. M. Bamberg, F. O'Donnell, C. J. Hoffmann, U. Fox, C. S. TI Association between single-slice measurements of visceral and abdominal subcutaneous adipose tissue with volumetric measurements: the Framingham Heart Study SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE abdominal adiposity; adipose tissue quantification; single-slice measurement; computed tomography; cardiovascular risk factors ID COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; METABOLIC SYNDROME; RISK-FACTORS; COMMUNITY; FAT AB Objective: Volumetric visceral abdominal adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAT) as measured by computed tomography (CT) are associated with metabolic risk factors. We sought to identify the correlations of VAT and SAT between area-based measures at different anatomic locations with volumetric measurements to identify the optimal anatomic site, and to relate measurements at this site with metabolic risk factors. Methods: We measured SAT and VAT volumes across the total imaging volume, whereas we measured SAT and VAT area at seven predefined anatomic landmarks in 200 participants from the Framingham Heart Study (mean age 54 years, 50% women) who underwent abdominal multi-detector CT. Correlation coefficients were used to assess the association between area measurements and volumes as well as metabolic risk factors stratified by gender. Results: Area-based measurements of SAT and VAT obtained at all anatomic landmarks were strongly associated with SAT and VAT volumes (all r>0.93, P<0.0001 and r>0.87, P<0.0001, for women and men; respectively). Consistently, area-based measurements of SAT and VAT obtained at L(3/4) were most strongly associated with volumetric measured VAT and SAT independent of age (both r=0.99 in men, r=0.96 for SAT and r=0.99 for VAT in women, all P-value <0.0001) and were similarly correlated with risk factors compared with SAT and VAT volumes (all P<0.05 for fasting plasma glucose, triglycerides, high-density lipoprotein, systolic blood pressure). Conclusion: Among area-based measurements of SAT and VAT, those obtained at the level of L(3/4) were strongly associated with SAT and VAT volumes and cardio-metabolic risk factors in both men and women. International Journal of Obesity (2010) 34, 781-787; doi: 10.1038/ijo.2009.279; published online 12 January 2010 C1 [O'Donnell, C. J.; Fox, C. S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Irlbeck, T.; Bamberg, F.; Hoffmann, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. [Massaro, J. M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [O'Donnell, C. J.] Harvard Univ, Sch Med, Dept Med, Cardiol Div,Massachusetts Gen Hosp, Boston, MA USA. [Fox, C. S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA. EM foxca@nlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195] FX This study was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195). NR 18 TC 38 Z9 44 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD APR PY 2010 VL 34 IS 4 BP 781 EP 787 DI 10.1038/ijo.2009.279 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 580WQ UT WOS:000276481700023 PM 20065971 ER PT J AU Marks, LB Cirrincione, C Fitzgerald, TJ Laurie, F Glicksman, AS Vredenburgh, J Prosnitz, LR Shpall, EJ Crump, M Richardson, PG Schuster, MW Ma, JL Peterson, BL Norton, L Seagren, S Henderson, IC Hurd, DD Peters, WP AF Marks, Lawrence B. Cirrincione, Constance Fitzgerald, Thomas J. Laurie, Frances Glicksman, Arvin S. Vredenburgh, James Prosnitz, Leonard R. Shpall, Elizabeth J. Crump, Michael Richardson, Paul G. Schuster, Michael W. Ma, Jinli Peterson, Bercedis L. Norton, Larry Seagren, Steven Henderson, I. Craig Hurd, David D. Peters, William P. CA Canc Leukemia Grp B SW Oncology Grp Natl Canc Inst Canada Clinical TI IMPACT OF HIGH-DOSE CHEMOTHERAPY ON THE ABILITY TO DELIVER SUBSEQUENT LOCAL-REGIONAL RADIOTHERAPY FOR BREAST CANCER: ANALYSIS OF CANCER AND LEUKEMIA GROUP B PROTOCOL 9082 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Breast cancer; Radiotherapy; High-dose chemotherapy; Toxicity ID AXILLARY LYMPH-NODES; BONE-MARROW-TRANSPLANTATION; COMPARING TOTAL MASTECTOMY; STEM-CELL TRANSPLANT; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; RACIAL-DIFFERENCES; RADIATION-THERAPY; FOLLOW-UP; POSTMASTECTOMY RADIOTHERAPY AB Purpose: To report, from Cancer and Leukemia Group B Protocol 9082, the impact of high-dose cyclophosphamide, cisplatin, and BCNU (HD-CPB) vs. intermediate-dose CPB (ID-CPB) on the ability to start and complete the planned course of local regional radiotherapy (RT) for women with breast cancer involving >= 10 axillary nodes. Methods and Materials: From 1991 to 1998, 785 patients were randomized. The HD-CPB and ID-CPB arms were balanced regarding patient characteristics. The HD-CPB and ID-CPB arms were compared on the probability of RT initiation, interruption, modification, or incompleteness. The impact of clinical variables and interactions between variables were also assessed. Results: Radiotherapy was initiated in 82% (325 of 394) of HD-CPB vs. 92% (360 of 391) of ID-CPB patients p = 0.001). On multivariate analyses, RT was less likely given to patients who were randomized to HD treatment (odds ratio [OR] = 0.38,p < 0.001), older (p = 0.005), African American (p = 0.003), postmastectomy (p = 0.02), or estrogen receptor positive (p = 0.03). High-dose treatment had a higher rate of RT interruption (21% vs. 12%, p = 0.001, OR = 2.05), modification (29% vs. 14%,p = 0.001, OR = 2.46), and early termination of RT (9% vs. 2%, p = 0.0001, OR = 5.35), compared with Ill. Conclusion: Treatment arm significantly related to initiation, interruption, modification, and early termination of RT. Patients randomized to HD-CPB were less likely to initiate RT, and of those who did, they were more likely to have RT interrupted, modified, and terminated earlier than those randomized to ID-CPB. The observed lower incidence of RT usage in African Americans vs. non African Americans warrants further study. (C) 2010 Elsevier Inc. C1 [Marks, Lawrence B.] Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. [Cirrincione, Constance; Peterson, Bercedis L.] Duke Univ, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. [Fitzgerald, Thomas J.] Univ Massachusetts, Dept Radiat Oncol, Worcester, MA 01605 USA. [Fitzgerald, Thomas J.; Laurie, Frances; Glicksman, Arvin S.] Qual Assurance Review Ctr, Providence, RI USA. [Glicksman, Arvin S.] Rhode Isl Canc Council, Pawtucket, RI USA. [Vredenburgh, James] Duke Univ, Dept Med Oncol, Durham, NC USA. [Marks, Lawrence B.; Prosnitz, Leonard R.; Ma, Jinli] Duke Univ, Dept Radiat Oncol, Durham, NC USA. [Shpall, Elizabeth J.] Univ Colorado, Adult Bone Marrow Transplant Program, Denver, CO 80202 USA. [Crump, Michael] Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada. [Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schuster, Michael W.] N Shore Long Isl Jewish Med Ctr, Manhasset, NY USA. [Ma, Jinli] Fudan Univ, Canc Hosp, Dept Radiat Oncol, Shanghai 200433, Peoples R China. [Norton, Larry] Mem Sloan Kettering Canc Ctr, Dept Solid Tumor Oncol, New York, NY 10021 USA. [Seagren, Steven] Univ Calif San Diego, Dept Radiat Oncol, San Diego, CA 92103 USA. [Henderson, I. Craig] Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. [Hurd, David D.] Wake Forest Univ, Dept Hematol, Winston Salem, NC 27109 USA. [Hurd, David D.] Wake Forest Univ, Dept Oncol, Winston Salem, NC 27109 USA. [Peters, William P.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. RP Marks, LB (reprint author), Univ N Carolina, Sch Med, Dept Radiat Oncol, CB 7512, Chapel Hill, NC 27599 USA. EM marks@med.unc.edu OI Norton, Larry/0000-0003-3701-9250 FU National Cancer Institute (NCI) [CA31946, CA33601, CA29511, CA47577, CA42777, CA77202, CA32291, CA35279, CA77651, CA11789, CA60138, CA03927, CA14028]; National Institutes of Health; Lance Armstrong Foundation; U.S. Department of Defense FX Supported by National Cancer Institute (NCI) Grants CA31946 (to Cancer and Leukemia Group B [CALBG], Richard L. Schilsky, Chairman), CA33601 (to the CALGB Statistical Center, Stephen George, Director), CA29511 (to the Quality Assurance Review Center), CA47577 (to J.V. and L.R.P.), CA42777 (to E.J.S.), CA77202 (to MC.). CA32291 (to P.G.R.), CA35279 (to M.W.S.), CA77651 (to L.N.), CA11789 (to S.S.), CA60138 (to I.C.H.), CA03927 (to D.D.H.), and CA14028 (to W.P.P.). This manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NCI.; L.B.M. receives honoraria from Varian Medical Systems, and grants from the National Institutes of Health, the Lance Armstrong Foundation, and the U.S. Department of Defense. P.G.R. receives an honorarium from Millennium Pharmaceuticals. NR 58 TC 2 Z9 2 U1 1 U2 2 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 APR 1 PY 2010 VL 76 IS 5 BP 1305 EP 1313 DI 10.1016/j.ijrobp.2009.04.013 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 583KZ UT WOS:000276675300007 PM 19747781 ER PT J AU Nanda, A Chen, MH Moran, BJ Braccioforte, MH Dosoretz, D Salenius, S Katin, M Ross, R D'Amico, AV AF Nanda, Akash Chen, Ming-Hui Moran, Brian J. Braccioforte, Michelle H. Dosoretz, Daniel Salenius, Sharon Katin, Michael Ross, Rudi D'Amico, Anthony V. TI TOTAL ANDROGEN BLOCKADE VERSUS A LUTEINIZING HORMONE-RELEASING HORMONE AGONIST ALONE IN MEN WITH HIGH-RISK PROSTATE CANCER TREATED WITH RADIOTHERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Prostate cancer; Prostate cancer-specific mortality; Androgen suppression therapy; External beam radiotherapy; Brachytherapy ID RANDOMIZED CONTROLLED-TRIAL; PHASE-III TRIAL; MODULATED RADIATION-THERAPY; QUALITY-OF-LIFE; DEFINITIVE RADIOTHERAPY; CONFORMAL RADIOTHERAPY; FREE SURVIVAL; FOLLOW-UP; SUPPRESSION; ADJUVANT AB Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone releasing hormone (LHRH) agonist alone affects the risk of prostate cancer specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy. Methods and Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score >= 8, or clinical category >= T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (inter-quartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors. Results: After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM. Conclusions: In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist. (C) 2010 Elsevier Inc. C1 [Nanda, Akash] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dana Farber Canc Inst, Boston, MA 02115 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Moran, Brian J.; Braccioforte, Michelle H.] Prostate Canc Fdn Chicago, Westmont, IL USA. [Dosoretz, Daniel; Salenius, Sharon; Katin, Michael; Ross, Rudi] 21st Century Oncol, Ft Myers, FL USA. RP Nanda, A (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dana Farber Canc Inst, 75 Francis St,ASB1 L2, Boston, MA 02115 USA. EM ananda@partners.org NR 31 TC 5 Z9 6 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 APR 1 PY 2010 VL 76 IS 5 BP 1439 EP 1444 DI 10.1016/j.ijrobp.2009.03.034 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 583KZ UT WOS:000276675300026 PM 19540066 ER PT J AU Hofstetter, B Niemierko, A Forrer, C Benhattar, J Albertini, V Pruschy, M Bosman, FT Catapano, CV Ciernik, IF AF Hofstetter, Barbara Niemierko, Andrzej Forrer, Christian Benhattar, Jean Albertini, Veronica Pruschy, Martn Bosman, Fred T. Catapano, Carlo V. Ciernik, I. Frank TI IMPACT OF GENOMIC METHYLATION ON RADIATION SENSITIVITY OF COLORECTAL CARCINOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Radiosensitization; Demethylation; Epigenomics; Colorectal Carcinoma; Ionizing Radiation ID CPG-ISLAND METHYLATION; DNA MISMATCH REPAIR; GENE-EXPRESSION; INCREASED RADIOSENSITIVITY; PROMOTER HYPERMETHYLATION; IONIZING-RADIATION; CANCER-THERAPY; LUNG-CANCER; CELL-LINES; IN-VIVO AB Purpose: To investigate the influence of demethylation with 5-aza-cytidine (AZA) on radiation sensitivity and to define the intrinsic radiation sensitivity of methylation deficient colorectal carcinoma cells. Methods and Materials: Radiation sensitizing effects of AZA were investigated in four colorectal carcinoma cell lines (HCT116, SW480, L174 T, Co115), defining influence of AZA on proliferation, clonogenic survival, and cell cycling with or without ionizing radiation. The methylation status for cancer or DNA damage response related genes silenced by promoter methylation was determined. The effect of deletion of the potential target genes (DNMT1, DNMT3b, and double mutants) on radiation sensitivity was analyzed. Results: AZA showed radiation sensitizing properties at >= 1 mu mol/l, a concentration that does not interfere with the cell cycle by itself, in all four tested cell lines with a sensitivity-enhancing ratio (SER) of 1.6 to 2.1 (confidence interval [CI] 0.9-3.3). AZA successfully demethylated promoters of p16 and hMLH1, genes associated with ionizing radiation response. Prolonged exposure to low-dose AZA resulted in sustained radiosensitivity if associated with persistent genomic hypomethylation after recovery from AZA. Compared with maternal HCT116 cells, DNMT3b-defcient deficient cells were more sensitive to radiation with a SER of 2.0 (CI 0.9-2.1; p = 0.03), and DNMT3b/DNMT1-/- double-deficient cells showed a SER of 1.6 (CI 0.5-2.7; p = 0.09). Conclusions: AZA-induced genomic hypomethylation results in enhanced radiation sensitivity in colorectal carcinoma. The mediators leading to sensitization remain unknown. Defining the specific factors associated with radiation sensitization after genomic demethylation may open the way to better targeting for the purpose of radiation sensitization. (C) 2010 Elsevier Inc. C1 [Hofstetter, Barbara; Forrer, Christian; Pruschy, Martn] Univ Zurich, Dept Radiat Oncol, Univ Zurich Hosp, Zurich, Switzerland. [Niemierko, Andrzej] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Niemierko, Andrzej] Harvard Univ, Sch Med, Boston, MA USA. [Benhattar, Jean; Bosman, Fred T.] CHU Vaudois, Dept Pathol, CH-1011 Lausanne, Switzerland. [Albertini, Veronica; Catapano, Carlo V.] Oncol Inst So Switzerland, Expt Oncol Lab, Bellinzona, Switzerland. [Ciernik, I. Frank] Univ Zurich, Univ Zurich Hosp, Clin Res Ctr, Zurich, Switzerland. RP Ciernik, IF (reprint author), Univ Spital Zurich, RAE E30,Ramistr 100, CH-8091 Zurich, Switzerland. EM ilja.ciernik@usz.ch FU Zurich Cancer League, Switzerland FX Supported in part by the Zurich Cancer League, Switzerland. NR 43 TC 27 Z9 30 U1 1 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 APR 1 PY 2010 VL 76 IS 5 BP 1512 EP 1519 DI 10.1016/j.ijrobp.2009.10.037 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 583KZ UT WOS:000276675300037 PM 20338477 ER PT J AU Moynihan, AL Varadarajan, KM Hanson, GR Park, SE Nha, KW Suggs, JF Johnson, T Li, GA AF Moynihan, Angela L. Varadarajan, Kartik M. Hanson, George R. Park, Sang-Eun Nha, Kyung Wook Suggs, Jeremy F. Johnson, Todd Li, Guoan TI In vivo knee kinematics during high flexion after a posterior-substituting total knee arthroplasty SO INTERNATIONAL ORTHOPAEDICS LA English DT Article ID CONDYLAR LIFT-OFF; FEMORAL COMPONENT; MOTION; RANGE; BIOMECHANICS; REPLACEMENT; PROSTHESIS; STANDARD; VITRO; HIP AB The objective of this study was to investigate biomechanics of TKA patients during high flexion. Six patients (seven knees) with a posterior-substituting TKA and weight-bearing flexion > 130A degrees were included in the study. The six degree-of-freedom kinematics, tibiofemoral contact, and cam-post contact were measured during a deep knee bend using dual-plane fluoroscopy. The patients achieved average weight-bearing flexion of 139.5 A +/- 4.5A degrees. Posterior femoral translation and internal tibial rotation increased steadily beyond 90A degrees flexion, and a sharp increase in varus rotation was noted at maximum flexion. Initial cam-post engagement was observed at 100.3 A +/- 6.7A degrees flexion. Five knees had cam-post disengagement before maximum flexion. Lateral femoral condylar lift-off was found in five out of seven knees at maximum flexion, and medial condylar lift-off was found in one knee. Future studies should investigate if the kinematic characteristics of posterior-substituting TKA knees noted in this study are causative factors of high knee flexion. C1 [Moynihan, Angela L.; Varadarajan, Kartik M.; Hanson, George R.; Suggs, Jeremy F.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Moynihan, Angela L.; Varadarajan, Kartik M.; Hanson, George R.; Suggs, Jeremy F.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Park, Sang-Eun] Dongguk Univ, Int Hosp, Dept Orthopaed Surg, Seoul 411773, South Korea. [Nha, Kyung Wook] Inje Univ, Dept Orthopaed Surg, Ilsan, South Korea. [Nha, Kyung Wook] Ilsanpaik Hosp, Ilsan, South Korea. [Varadarajan, Kartik M.; Suggs, Jeremy F.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Johnson, Todd] Zimmer Inc, Warsaw, IN 46581 USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU Zimmer Inc., Warsaw, IN, USA FX This work was supported by a research grant from Zimmer Inc., Warsaw, IN, USA. NR 24 TC 22 Z9 25 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 J9 INT ORTHOP JI Int. Orthop. PD APR PY 2010 VL 34 IS 4 BP 497 EP 503 DI 10.1007/s00264-009-0777-2 PG 7 WC Orthopedics SC Orthopedics GA 571LT UT WOS:000275754000006 PM 19387643 ER PT J AU Lu, B Wang, SM Francis, PJ Li, TS Gamm, DM Capowski, EE Lund, RD AF Lu, Bin Wang, Shaomei Francis, Peter J. Li, Tiansen Gamm, David M. Capowski, Elizabeth E. Lund, Raymond D. TI Cell Transplantation to Arrest Early Changes in an Ush2a Animal Model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HUMAN NEURAL PROGENITORS; USHER-SYNDROME; RETINITIS-PIGMENTOSA; RAT RETINA; RCS RAT; PHOTORECEPTOR DEGENERATION; MACULAR DEGENERATION; VISUAL FUNCTIONS; DISEASE; VISION AB PURPOSE. Usher's syndrome is a combined deafness and blindness disorder caused by mutations in several genes with functions in both the retina and the ear. Here the authors studied morphologic and functional changes in an animal model, the Ush2a mouse, and explored whether transplantation of fore-brain-derived progenitor cells might affect the progress of morphologic and functional deterioration. METHODS. Ush2a mice were tested at postnatal days (P) 70 to P727 using an optomotor test, which provides a repeatable method of estimating rodent visual acuity and contrast sensitivity. A group of mice that received grafts of forebrain-derived progenitor cells at P80 was tested for up to 10 weeks after grafting. At the end of testing, animals were killed, and eyes were processed for histology. RESULTS. The optomotor test showed that both acuity and contrast sensitivity deteriorated over time; contrast sensitivity showed a deficit even at P70. By contrast, photoreceptor loss was only evident later than 1 year of age, though changes in the intracellular distribution of red/green cone opsin were observed as early as P80. Mice that received transplanted cells performed significantly better than control mice and no longer demonstrated abnormal distribution of red/green opsin where the donor cells were distributed. CONCLUSIONS. This study showed that vision impairment was detected well before significant photoreceptor loss and was correlated with abnormal distribution of a cone pigment. Cell transplantation prevented functional deterioration for at least 10 weeks and reversed the mislocalization of cone pigment. (Invest Ophthalmol Vis Sci. 2010;51:2269-2276) DOI:10.1167/iovs.09-4526 C1 [Lu, Bin; Wang, Shaomei; Francis, Peter J.; Lund, Raymond D.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA. [Li, Tiansen] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. [Gamm, David M.; Capowski, Elizabeth E.] Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. [Lund, Raymond D.] Univ Utah, Moran Eye Ctr, Salt Lake City, UT USA. RP Lund, RD (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, 3181 SW Sam Jackson Pk Rd,BRB,L467RT, Portland, OR 97239 USA. EM lundr@ohsu.edu FU Hear See Hope; Foundation Fighting Blindness; Research to Prevent Blindness; Walsh Foundation FX Supported by Hear See Hope, Foundation Fighting Blindness, Research to Prevent Blindness, and Walsh Foundation. NR 32 TC 11 Z9 11 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2010 VL 51 IS 4 BP 2269 EP 2276 DI 10.1167/iovs.09-4526 PG 8 WC Ophthalmology SC Ophthalmology GA 574ND UT WOS:000275995800061 PM 19959642 ER PT J AU Prakash, P Kalra, MK Kambadakone, AK Pien, H Hsieh, J Blake, MA Sahani, DV AF Prakash, Priyanka Kalra, Mannudeep K. Kambadakone, Avinash K. Pien, Homer Hsieh, Jiang Blake, Michael A. Sahani, Dushyant V. TI Reducing Abdominal CT Radiation Dose With Adaptive Statistical Iterative Reconstruction Technique SO INVESTIGATIVE RADIOLOGY LA English DT Article DE abdominal CT; interative reconstruction; ASIR; radiation dose ID COMPUTED-TOMOGRAPHY; IMAGE-QUALITY; ROW CT; REDUCTION; OPTIMIZATION; ANGIOGRAPHY; NOISE; CHEST AB Purpose: To assess radiation dose reduction for abdominal computed tomography (CT) examinations with adaptive statistical iterative reconstruction (ASIR) technique. Materials and Methods: With institutional review board approval, retrospective review of weight adapted abdominal CT exams were performed in 156 consecutive patients with ASIR and in 66 patients with filtered back projection (FBP) on a 64-slice MDCT. Patients were categorized into 3 groups of < 60 kg (n = 42), 61 to 90 kg (n = 100), and >= 91 kg (n = 80) for weight-based adjustment of automatic exposure control technique. Remaining scan parameters were held constant at 1.375:1 pitch, 120 kVp, 55 mm table feed per rotation, 5 mm section thickness. Two radiologists reviewed all CT examinations for image noise and diagnostic acceptability. CT dose index volume, and dose length product were recorded. Image noise and transverse abdominal diameter were measured in all patients. Data were analyzed using analysis of variance. Results: ASIR allowed for an overall average decrease of 25.1% in CT dose index volume compared with the FBP technique (ASIR, 11.9 +/- 3.6 mGy; FBP, 15.9 +/- 4.3 mGy) (P < 0.0001). In each of the 3 weight categories, CT examinations reconstructed with ASIR technique were associated with significantly lower radiation dose compared with FBP technique (P < 0.0001). There was also significantly less objective image noise with ASIR (6.9 +/- 2.2) than with FBP (9.5 +/- 2.0) (P < 0.0001). For the subjective analysis, all ASIR and FBP reconstructed abdominal CTs had optimal or less noise. However, 9% of FBP and 3.8% of ASIR reconstructed CT examinations were diagnostically unacceptable because of the presence of artifacts. Use of ASIR reconstruction kernel results in a blotchy pixilated appearance in 39% of CT sans which however, was mild and did not affect the diagnostic acceptability of images. The critical reproduction of visually sharp anatomic structures was preserved in all but one ASIR 40% reconstructed CT examination. Conclusion: ASIR technique allows radiation dose reduction for abdominal CT examinations whereas improving image noise compared with the FBP technique. C1 [Prakash, Priyanka; Kalra, Mannudeep K.; Kambadakone, Avinash K.; Pien, Homer; Blake, Michael A.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Prakash, Priyanka; Kalra, Mannudeep K.; Kambadakone, Avinash K.; Pien, Homer; Blake, Michael A.; Sahani, Dushyant V.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hsieh, Jiang] GE Healthcare, Waukesha, WI USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org FU GE Healthcare (Waukesha, WI) FX Supported by GE Healthcare (Waukesha, WI) (to M. K. K. and D. V. S.). NR 18 TC 227 Z9 257 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD APR PY 2010 VL 45 IS 4 BP 202 EP 210 DI 10.1097/RLI.0b013e3181dzfeec PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 579ML UT WOS:000276374800006 PM 20177389 ER PT J AU Rogers, IS Nasir, K Figueroa, AL Cury, RC Hoffmann, U Vermylen, DA Brady, TJ Tawakol, A AF Rogers, Ian S. Nasir, Khurram Figueroa, Amparo L. Cury, Ricardo C. Hoffmann, Udo Vermylen, David A. Brady, Thomas J. Tawakol, Ahmed TI Feasibility of FDG Imaging of the Coronary Arteries Comparison Between Acute Coronary Syndrome and Stable Angina SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE 18-fluorodeoxyglucose positron emission tomography; cardiac computed tomography; aorta; coronary arteries; inflammation ID POSITRON-EMISSION-TOMOGRAPHY; ATHEROSCLEROTIC PLAQUE INFLAMMATION; HIGH-FAT; MYOCARDIAL-INFARCTION; LOW-CARBOHYDRATE; F-18-FDG UPTAKE; PET; DISEASE; SUPPRESSION; PROGRESSION AB OBJECTIVES This study tested the hypothesis that fluorodeoxyglucose (FDG) uptake within the ascending aorta and left main coronary artery (LM), measured using positron emission tomography (PET), is greater in patients with recent acute coronary syndrome (ACS) than in patients with stable angina. BACKGROUND Inflammation is known to play an important role in atherosclerosis. Positron emission tomography imaging with (18)F-FDG provides a measure of plaque inflammation. METHODS Twenty-five patients (mean age 57.9 +/- 9.8 years, 72% male, 10 ACS, and 15 stable angina) underwent cardiac computed tomographic angiography and PET imaging with (18)F-FDG after invasive angiography. Images were coregistered, and FDG uptake was measured at locations of interest for calculation of target-to-background ratios (TBR). Additionally, FDG uptake was measured at the site of the lesion deemed clinically responsible for the presenting syndrome (culprit) by virtue of locating the stent deployed to treat the syndrome. RESULTS The FDG uptake was higher in the ACS versus the stable angina groups in the ascending aorta (median [interquartile ranges] TBR 3.30 [2.69 to 4.12] vs. 2.43 [2.00 to 2.86], p = 0.02), as well as the LM (2.48 [2.30 to 2.93] vs. 2.00 [1.71 to 2.44], p = 0.03, respectively). The TBR was greater for culprit lesions associated with ACS than for lesions stented for stable coronary syndromes (2.61 vs. 1.74, p = 0.02). Furthermore, the TBR in the stented lesions (in ACS and stable angina groups) correlated with C-reactive protein (r = 0.58, p = 0.04). CONCLUSIONS This study shows that in patients with recent ACS, FDG accumulation is increased both within the culprit lesion as well as in the ascending aorta and LM. This observation suggests inflammatory activity within atherosclerotic plaques in acute coronary syndromes and supports intensification of efforts to refine PET methods for molecular imaging of coronary plaques. (J Am Coll Cardiol Img 2010;3:388-97) (C) 2010 by the American College of Cardiology Foundation C1 [Tawakol, Ahmed] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program,Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Tawakol, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program,Div Cardiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM atawakol@partners.org FU National Institutes of Health [T32HL076136]; Center for Integration of Medicine and Innovative Technologies FX Drs. Rogers and Nasir received support from National Institutes of Health grant T32HL076136. Dr. Tawakol received support from the Center for Integration of Medicine and Innovative Technologies. NR 31 TC 135 Z9 137 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD APR PY 2010 VL 3 IS 4 BP 388 EP 397 DI 10.1016/j.jcmg.2010.01.004 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 647NT UT WOS:000281625900009 PM 20394901 ER PT J AU Maurovich-Horvat, P Hoffmann, U Vorpahl, M Nakano, M Virmani, R Alkadhi, H AF Maurovich-Horvat, Pal Hoffmann, Udo Vorpahl, Marc Nakano, Masataka Virmani, Renu Alkadhi, Hatem TI The Napkin-Ring Sign: CT Signature of High-Risk Coronary Plaques? SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material C1 [Maurovich-Horvat, Pal; Hoffmann, Udo; Alkadhi, Hatem] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Maurovich-Horvat, Pal; Hoffmann, Udo; Alkadhi, Hatem] Harvard Univ, Sch Med, Boston, MA USA. [Maurovich-Horvat, Pal] Semmelweis Univ, Ctr Heart, Budapest, Hungary. [Hoffmann, Udo; Vorpahl, Marc; Nakano, Masataka; Virmani, Renu] CV Path Inst Inc, Gaithersburg, MD USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org NR 8 TC 46 Z9 46 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD APR PY 2010 VL 3 IS 4 BP 440 EP 444 DI 10.1016/j.jcmg.2010.02.003 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 647NT UT WOS:000281625900014 PM 20394906 ER PT J AU Goetz, MB Leduc, R Wyman, N Kostman, JR Labriola, AM Lie, Y Weidler, J Coakley, E Bates, M Luskin-Hawk, R AF Goetz, Matthew Bidwell Leduc, Robert Wyman, Nicole Kostman, Jay R. Labriola, Ann M. Lie, Yolanda Weidler, Jodi Coakley, Eoin Bates, Michael Luskin-Hawk, Roberta CA Long Term Monitoring Study CPCRA0 TI HIV Replication Capacity Is an Independent Predictor of Disease Progression in Persons With Untreated Chronic HIV Infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE disease progression; HIV infections; natural history; replication ID IMMUNODEFICIENCY-VIRUS TYPE-1; PHENOTYPIC DRUG SUSCEPTIBILITY; INHIBITOR-RESISTANT HIV-1; LONG-TERM SURVIVORS; VIRAL FITNESS; CORECEPTOR TROPISM; CELL COUNTS; PROTEASE; THERAPY; LOAD AB Objective: To assess the effect of pol replication capacity (RC) on the hazard ratio of progression to a composite endpoint of time to progression to < 350 CD4(+) cells per microliter, initiation of therapy, or death. Methods: pol RC assays were performed after study closure in baseline samples obtained from 316 enrollees in a prospectively monitored cohort of treatment-naive adults with >= 450 CD4(+) cells per microliter and >= 1000 HIV-1 RNA copies per milliliter. Results: The median RC was 79%. Patients with a lower RC had a lower median viral load (4.0 vs 4.2 Log HIV-1 RNA copies/mL, P = 0.026) and a lower rate of protease inhibitor resistance 2% vs 8%, P = 0.03). Otherwise, baseline demographic and laboratory characteristics were similar. The hazard ratio of progression to the composite endpoint was 0.73 ( P = 0.041) for persons with lower RC, 2.07 per 1.0 log(10) higher viral load (P < 0.001), and 0.86 per 50 cells per microliter higher CD4(+) cell count (P < 0.001). The effect of lower RC was also significant in a separate analysis of time to initiation of therapy (P = 0.04). Conclusions: These results show that untreated patients with lower vs higher RC had a slower rate of progression as assessed by a composite outcome of time to CD4(+) count <= 350 cells per microliter, treatment initiation, or death. C1 [Goetz, Matthew Bidwell] Vet Affairs Greater Los Angeles Healthcare Syst, Infect Dis Sect 111 F, Dept Med, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Leduc, Robert; Wyman, Nicole] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Kostman, Jay R.] Univ Penn Hlth Syst, Presbyterian Med Ctr, Dept Med, Philadelphia, PA USA. [Labriola, Ann M.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Labriola, Ann M.] Vet Affairs Med Ctr, Dept Med, Washington, DC 20422 USA. [Lie, Yolanda; Weidler, Jodi; Coakley, Eoin; Bates, Michael] Monogram Biosci, San Francisco, CA USA. [Luskin-Hawk, Roberta] St Joseph Hosp, Dept Med, Chicago, IL USA. RP Goetz, MB (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Infect Dis Sect 111 F, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM matthew.goetz@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU National Institute of Allergy and Infectious Diseases [U01 AI042170, U01 AI046362, U01 AI068641]; SBIR [R44AI050321] FX Supported by National Institute of Allergy and Infectious Diseases grants U01 AI042170, U01 AI046362, and U01 AI068641 to the Community Programs for Clinical Research on AIDS and SBIR R44AI050321 to Monogram Biosciences. NR 40 TC 6 Z9 6 U1 1 U2 5 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 1 PY 2010 VL 53 IS 4 BP 472 EP 479 DI 10.1097/QAI.0b013e3181cae480 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 567YW UT WOS:000275486600006 PM 20032783 ER PT J AU Pompili, M Baldessarini, RJ Tondo, L Innamorati, M Tatarelli, R Girardi, P De Pisa, E AF Pompili, Maurizio Baldessarini, Ross J. Tondo, Leonardo Innamorati, Marco Tatarelli, Roberto Girardi, Paolo De Pisa, Eleonora TI Response to intravenous antidepressant treatment by suicidal vs. nonsuicidal depressed patients SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Depression; Intravenous antidepressants; Major affective disorders; Suicide; Treatment response ID SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIALS; CLINICAL-TRIALS; RISK; IDEATION; PLACEBO; METAANALYSIS; CITALOPRAM; REDUCTION; DISORDER AB Background: As effects of suicidal status on antidepressant responses remain uncertain, we compared responses to treatment in suicidal and nonsuicidal depressed patients. Methods: We evaluated treatment response and covariates in 82 depressed patients diagnosed with DSM-IV major depressive (n = 50) or bipolar disorders (n = 32) treated initially in a day-hospital for 2 weeks, followed by 4 weeks of outpatient treatment, using citalopram given intravenously and then orally, with or without a mood-stabilizer. Suicidal status was based on an intake score of >= 3 on item-3 of the 17-item Hamilton Depression Rating Scale, verified by clinical assessment. Morbidity and clinical change were assessed with the remaining 16 items (HDRS(16)). Results: Suicidal (n = 31) and nonsuicidal subjects (n = 51) were similar in baseline ratings of depressive symptom-severity but were depressed longer and more likely to abuse substances. Suicidal ratings improved by 36% during 6 weeks of treatment among initially suicidal patients, but other depressive symptoms (HDRS(16)) improved half as much as in nonsuicidal subjects (13.4 vs. 25.1 points), independent of diagnosis, initial illness-severity, and treatment, and half as many patients improved by >= 20%. In multivariate modeling, only being suicidal predicted poor response. Conclusions: Being suicidal may limit response to treatment in depressed major affective disorder patients, independent of diagnosis or overall symptomatic severity. (C) 2009 Elsevier B.V. All rights reserved. C1 [Pompili, Maurizio; Innamorati, Marco; Tatarelli, Roberto; Girardi, Paolo; De Pisa, Eleonora] Univ Roma La Sapienza, St Andrea Hosp, Dept Psychiat, I-00189 Rome, Italy. [Pompili, Maurizio; Baldessarini, Ross J.; Tondo, Leonardo] Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Belmont, MA 02478 USA. [Pompili, Maurizio; Baldessarini, Ross J.; Tondo, Leonardo] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. [Tondo, Leonardo] Univ Cagliari, Dept Psychol, Cagliari, Italy. [Tondo, Leonardo] Ctr Lucio Bini Mood Disorders Res Ctr, Cagliari, Italy. [Innamorati, Marco] Univ Europea Roma, Rome, Italy. RP Pompili, M (reprint author), Univ Roma La Sapienza, St Andrea Hosp, Dept Psychiat, Via Grottarossa 1035, I-00189 Rome, Italy. EM maurizio.pompili@uniroma1.it RI Innamorati, Marco/H-8877-2013; OI Innamorati, Marco/0000-0003-1389-2290; Tatarelli, Roberto/0000-0003-4396-2632; Pompili, Maurizio/0000-0003-1886-4977 FU Bruce J. Anderson Foundation; McLean Private Donors Psychopharmacology Research Fund FX Supported in part by a grant from the Bruce J. Anderson Foundation and the McLean Private Donors Psychopharmacology Research Fund (to RJB). NR 36 TC 2 Z9 2 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2010 VL 122 IS 1-2 BP 154 EP 158 DI 10.1016/j.jad.2009.07.018 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 587HE UT WOS:000276980200021 PM 19709752 ER PT J AU Siev, J Chambless, DL Huppert, JD AF Siev, Jedidiah Chambless, Dianne L. Huppert, Jonathan D. TI Moral thought-action fusion and OCD symptoms: The moderating role of religious affiliation SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Obsessive-compulsive disorder; Thought action fusion; Religion; Religiosity; Cognitions; Scrupulosity ID OBSESSIVE-COMPULSIVE DISORDER; PSYCHOMETRIC PROPERTIES; CLINICAL-SAMPLE; COGNITIONS; SCRUPULOSITY; VALIDATION; INVENTORY; VALIDITY AB The empirical literature on the relationship between moral thought-action fusion (TAF) and obsessive-compulsive disorder (OCD) is characterized by mixed findings. Previous studies have reported religious group differences in moral TAF and the relationship between moral TAF and religiosity. In light of those studies and considering the apparent role of moral TAF in scrupulosity, the purpose of this investigation was to evaluate the possible role of religion as a moderator of the relationship between moral TAF and OCD symptoms. The results revealed that (a) Christians endorsed higher levels of moral TAF than did Jews independent of OCD symptoms; (b) religiosity was correlated with moral TAF in Christians but not in Jews, suggesting that Christian religious adherence is related to beliefs about the moral import of thoughts; and (c) moral TAF was related to OCD symptoms only in Jews. That is, for Christians, moral TAF was related to religiosity but not OCD symptoms, and for Jews, moral TAF was related to OCD symptoms but not religiosity. These results imply that moral TAF is only a marker of pathology when such beliefs are not culturally normative (e.g., as a function of religious teaching or doctrine). (C) 2010 Elsevier Ltd. All rights reserved. C1 [Siev, Jedidiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Siev, Jedidiah; Chambless, Dianne L.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Huppert, Jonathan D.] Hebrew Univ Jerusalem, Dept Psychol, IL-93509 Jerusalem, Israel. RP Siev, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 185 Cambridge St,2nd Floor, Boston, MA 02114 USA. EM jsiev@partners.org; chambless@psych.upenn.edu; huppertj@mscc.huji.ac.il RI Chambless, Dianne/A-1065-2007; OI Huppert, Jonathan/0000-0002-0537-4701 NR 20 TC 20 Z9 20 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD APR PY 2010 VL 24 IS 3 BP 309 EP 312 DI 10.1016/j.janxdis.2010.01.002 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 575GJ UT WOS:000276054700003 PM 20097516 ER PT J AU Nishikawa, K Duncan, MJ AF Nishikawa, Kiyoshi Duncan, Margaret J. TI Histidine Kinase-Mediated Production and Autoassembly of Porphyromonas gingivalis Fimbriae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ANAEROBE BACTEROIDES-GINGIVALIS; 2-COMPONENT SIGNAL-TRANSDUCTION; EPITHELIAL-CELLS; FIMA GENOTYPES; RESPONSE REGULATOR; GENOME SEQUENCE; OUTER-MEMBRANE; STRAIN W83; VIRULENCE; GENE AB Porphyromonas gingivalis, a Gram-negative oral anaerobe, is strongly associated with chronic adult periodontitis, and it utilizes FimA fimbriae to persistently colonize and evade host defenses in the periodontal crevice. The FimA-related gene cluster (the fim gene cluster) is positively regulated by the FimS-FimR two-component system. In this study, comparative analyses between fimbriate type strain ATCC 33277 and fimbria-deficient strain W83 revealed differences in their fimS loci, which encode FimS histidine kinase. Using a reciprocal gene exchange system, we established that FimS from W83 is malfunctional. Complementation analysis with chimeric fimS constructs revealed that W83 FimS has a defective kinase domain due to a truncated conserved G3 box motif that provides an ATP-binding pocket. The introduction of the functional fimS from 33277 restored the production, but not polymerization, of endogenous FimA subunits in W83. Further analyses with a fimA-exchanged W83 isogenic strain showed that even the fimbria-deficient W83 retains the ability to polymerize FimA from 33277, indicating the assembly of mature FimA by a primary structure-dependent mechanism. It also was shown that the substantial expression of 33277-type FimA fimbriae in the W83 derivative requires the introduction and expression of the functional 33277 fimS. These findings indicate that FimSR is the unique and universal regulatory system that activates the fim gene cluster in a fimA genotype-independent manner. C1 [Nishikawa, Kiyoshi] Aichi Gakuin Univ, Sch Dent, Dept Microbiol, Chikusa Ku, Nagoya, Aichi 4648650, Japan. [Duncan, Margaret J.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Nishikawa, K (reprint author), Aichi Gakuin Univ, Sch Dent, Dept Microbiol, Chikusa Ku, 1-100 Kusumoto Cho, Nagoya, Aichi 4648650, Japan. EM niski@dpc.agu.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology, Japan [19592139]; NIH [DE015931] FX We thank T. Hirose of the Center for Instrumental Analysis, Hokkaido University, for help with N-terminal amino acid sequencing. Anti-type I FimA antiserum was provided by F. Yoshimura.; This work was supported by a Grant-in-Aid for Scientific Research (KAKENHI 19592139 to K.N.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and by NIH grant DE015931 to M. D. NR 44 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2010 VL 192 IS 7 BP 1975 EP 1987 DI 10.1128/JB.01474-09 PG 13 WC Microbiology SC Microbiology GA 568NK UT WOS:000275529100024 PM 20118268 ER PT J AU Massimini, DF Li, GA Warner, JP AF Massimini, Daniel F. Li, Guoan Warner, Jon P. TI Glenohumeral Contact Kinematics in Patients After Total Shoulder Arthroplasty SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID RETRIEVED GLENOID COMPONENTS; ARTICULAR-CARTILAGE CONTACT; CONSTANT SCORE; HUMERAL HEAD; REPLACEMENT ARTHROPLASTY; SCAPULOHUMERAL RHYTHM; SURGICAL TECHNIQUE; PROSTHETIC DESIGN; JOINT KINEMATICS; REACTION FORCES AB Background: Knowledge of in vivo glenohumeral joint contact mechanics after total shoulder arthroplasty may provide insight for the improvement of patient function, implant longevity, and surgical technique. The objective of this study was to determine the in vivo glenohumeral joint contact locations in patients after total shoulder arthroplasty. We hypothesized that the glenohumeral joint articular contact would be centered on the glenoid surface because of the ball-in-socket geometric features of the implants. Methods: Dual-plane fluoroscopic images and computer-aided design models were used to quantify patient-specific glenohumeral articular contact in thirteen shoulders following total shoulder arthroplasty. The reconstructed shoulder was imaged at arm positions of 0 degrees, 45 degrees, and 90 degrees of abduction (in the coronal plane) and neutral rotation and at 90 degrees of abduction with maximum internal and external rotation. The patients were individually investigated, and their glenohumeral joint contact centroids were reported with use of contact frequency. Results: In all positions, the glenohumeral joint contact centroids were not found at the center of the glenoid surface but at an average distance (and standard deviation) of 11.0 +/- 4.3 mm from the glenoid center. Forty (62%) of the sixty-five total contact occurrences were found on the superior-posterior quadrant of the glenoid surface. The position of 0 degrees of abduction in neutral rotation exhibited the greatest variation of quadrant contact location; however, no contact was found on the superior-anterior quadrant of the glenoid surface in this position. Conclusions: In vivo, glenohumeral joint contact after total shoulder arthroplasty is not centered on the glenoid surface, suggesting that kinematics after shoulder arthroplasty may not be governed by ball-in-socket mechanics as traditionally thought. Although contact locations as a function of arm position vary among patients, the superior-posterior quadrant seems to experience the most articular contact in the shoulder positions tested. C1 Massachusetts Gen Hosp, Bioengn Lab, Boston, MA 02114 USA. RP Massimini, DF (reprint author), Massachusetts Gen Hosp, Bioengn Lab, GRJ 1215,55 Fruit Str, Boston, MA 02114 USA. EM gli1@partners.org NR 76 TC 16 Z9 16 U1 2 U2 5 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 2010 VL 92A IS 4 BP 916 EP 926 DI 10.2106/JBJS.H.01610 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 581MD UT WOS:000276526400018 PM 20360516 ER PT J AU Wigner, NA Luderer, HF Cox, MK Sooy, K Gerstenfeld, LC Demay, MB AF Wigner, Nathan A. Luderer, Hilary F. Cox, Megan K. Sooy, Karen Gerstenfeld, Louis C. Demay, Marie B. TI Acute Phosphate Restriction Leads to Impaired Fracture Healing and Resistance to BMP-2 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE RODENT; FRACTURE; BMP; ENDOCHONDRAL; INTRAMEMBRANOUS; HYPOPHOSPHATEMIA ID MORPHOGENETIC PROTEIN-2 EXPRESSION; RICKETS TYPE-II; BONE-FORMATION; OSTEOBLAST DIFFERENTIATION; HYPERTROPHIC CHONDROCYTES; STEM-CELLS; REPAIR; LIMB; HYPOPHOSPHATEMIA; INHIBITION AB Hypophosphatemia leads to rickets and osteomalacia, the latter of which results in decreased biomechanical integrity of bones, accompanied by poor fracture healing Impaired phosphate-dependent apoptosis of hypertrophic chondrocytes is the molecular basis for rickets. However, the underlying pathophysiology of impaired fracture healing has not been characterized previously To address the role of phosphate in fracture repair, mice were placed on a phosphate-restricted diet 2 days prior to or 3 days after induction of a mid-diaphyseal femoral fracture to assess the effects of phosphate deficiency on the initial recruitment of mesenchymal stem cells and their subsequent differentiation. Histologic and micro-computed tomographic (mu CT) analyses demonstrated that both phosphate restriction models dramatically impaired fracture healing primarily owing to a defect in differentiation along the chondrogenic lineage Based on Sox9 and Sox5 mRNA levels, neither the initial recruitment of cells to the callus nor their lineage commitment was effected by hypophosphatemia However, differentiation of these cells was impaired in association with impaired bone morphogenetic protein (BMP) signaling In vivo ectopic bone-formation assays and in vitro investigations in ST2 stromal cells confirmed that phosphate restriction leads to BMP-2 resistance. Marrow ablation studies demonstrate that hypophosphatemia has different effects on injury-induced intramembranous bone formation compared with endochondral bone formation Thus phosphate plays an important role in the skeleton that extends beyond mineralized matrix formation and growth plate maturation and is critical for endochondral bone repair (C) 2010 American Society for Bone and Mineral Research. C1 [Luderer, Hilary F.; Cox, Megan K.; Sooy, Karen; Demay, Marie B.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Luderer, Hilary F.; Cox, Megan K.; Sooy, Karen; Demay, Marie B.] Harvard Univ, Sch Med, Boston, MA USA. [Wigner, Nathan A.; Gerstenfeld, Louis C.] Boston Univ, Med Ctr, Orthopaed Res Lab, Dept Orthopaed Surg, Boston, MA USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 11,50 Blossom St, Boston, MA 02114 USA. OI /0000-0002-0477-1211 FU National Institutes of Health [DK46974] FX We would like to thank L Silkman and ED Zhu for technical assistance and C Bergwitz for helpful discussions We are also grateful to Wyeth for providing the rhBMP-2 for the ectopic BFAs These studies were funded by a grant from the National Institutes of Health (DK46974) NR 43 TC 10 Z9 10 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2010 VL 25 IS 4 BP 724 EP 733 DI 10.1359/jbmr.091021 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 589YF UT WOS:000277189400006 PM 19839770 ER PT J AU Kim, WK Meliton, V Tetradis, S Weinmaster, G Hahn, TJ Carlson, M Nelson, SF Parhami, F AF Kim, Woo-Kyun Meliton, Vicente Tetradis, Sotirios Weinmaster, Gerry Hahn, Theodore J. Carlson, Marc Nelson, Stanley F. Parhami, Farhad TI Osteogenic Oxysterol, 20(S)-Hydroxycholesterol, Induces Notch Target Gene Expression in Bone Marrow Stromal Cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE OXYSTEROL; MESENCHYMAL STEM CELLS; NOTCH; HEDGEHOG; OSTEOGENESIS ID INDUCED OSTEOBLASTIC DIFFERENTIATION; VASCULAR DEVELOPMENT; SIGNALING PATHWAYS; SONIC-HEDGEHOG; IN-VIVO; HES-1; FATE; HEY1; INTEGRATION; ACTIVATION AB We previously reported that specific oxysterols stimulate osteogenic differentiation of pluripotent bone marrow stromal cells (MSCs) through activation of hedgehog (Hh) signaling and may serve as potential future therapies for intervention in osteopenia and osteoporosis. In this study we report that the osteogenic oxysterol 20(S)-hydroxycholesterol (20S) induces the expression of genes associated with Notch signaling. Using M2-10B4 (M2) MSCs, we found that 20S significantly induced HES-1, HEY-1, and HEY-2 mRNA expression compared with untreated cells, with maximal induction after 48 hours, whereas the nonosteogenic oxysterols did not Similar observations were made when M2 cells were treated with sonic hedgehog (Shh), and the specific Hh pathway inhibitor cyclopamine blocked 20S-induced Notch target gene expression. 20S did not induce Notch target genes in Smo(-/-) mouse embryonic fibroblasts, further confirming the role of Hh signaling in 20S-induced expression of Notch target genes. Despite the inability of liver X-receptor (LXR) synthetic ligand TO901317 to induce Notch target genes in M2 cells, LXR knockdown studies using siRNA showed inhibition of 20S-induced HEY-1 but not HES-1 expression, suggesting the partial role of LXR signaling in MSC responses to 20S Moreover, 20S-induced Notch target gene expression was independent of canonical Notch signaling because neither 20S nor Shh induced CBF1 luaferase reporter activity or NICD protein accumulation in the nucleus, which are hallmarks of canonical Notch signaling activation Finally, HES-1 and HEY-1 siRNA transfection significantly inhibited 20S-induced osteogenic genes, suggesting that the pro-osteogenic effects of 20S are regulated in part by HES-1 and HEY-1. (C) 2010 American Society for Bone and Mineral Research. C1 [Kim, Woo-Kyun; Meliton, Vicente; Parhami, Farhad] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Tetradis, Sotirios] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA. [Weinmaster, Gerry] Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. [Hahn, Theodore J.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hahn, Theodore J.] Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. [Carlson, Marc; Nelson, Stanley F.] Univ Calif Los Angeles, Dept Human Genet, Sch Med, Los Angeles, CA 90095 USA. RP Parhami, F (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci, A2-237 10833 Le Conte Ave, Los Angeles, CA 90095 USA. RI Nelson, Stanley/D-4771-2009 FU NIAMS, National Institutes of Health (NIH) [RO1 AR050426]; National Institute of Aging [5P30AG028748] FX This work was supported in part by NIAMS, National Institutes of Health (NIH) Grant RO1 AR050426, and a Pilot Study Award from the UCLA Claude Pepper Older American Independence Center funded by the National Institute of Aging Grant 5P30AG028748 We thank Dr Philip Beachy (Stanford University) for providing the Smo-/- MEFs We are grateful to Brendan D'Souza (UCLA Department of Biological Chemistry) for critical review of this manuscript and insightful discussions NR 47 TC 15 Z9 15 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2010 VL 25 IS 4 BP 782 EP 795 DI 10.1359/jbmr.091024 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 589YF UT WOS:000277189400011 PM 19839776 ER PT J AU Costanzo, MR Saltzberg, MT Jessup, M Teerlink, JR Sobotka, PA AF Costanzo, Maria Rosa Saltzberg, Mitchell T. Jessup, Mariell Teerlink, John R. Sobotka, Paul A. CA Ultrafiltration Versus Intravenous TI Ultrafiltration is Associated With Fewer Rehospitalizations than Continuous Diuretic Infusion in Patients With Decompensated Heart Failure: Results From UNLOAD SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Ultrafiltration; diuretics; heart failure ID BODY-FLUID; FUROSEMIDE; RESISTANCE; OUTCOMES; REGISTRY; TRIAL; DEATH AB Background: Compare outcomes of ultrafiltration (UF) versus standard intravenous (IV) diuretics by continuous infusion or bolus injection in volume overloaded heart failure (HF) patients. In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated heart Failure (UNLOAD) study, UF produced greater fluid reduction and fewer HF rehospitalizations than IV diuretics in 200 hospitalized HF patients. Outcomes may be due to greater fluid removal, but UF removes more sodium/unit volume than diuretics. Methods and Results: Outcomes of 100 patients randomized to UF were compared with those of patients randomized to standard IV diuretic therapy with continuous infusion (32) or bolus injections (68). Choice of diuretic therapy was by the treating physician. Forty-eight hour weight loss (kg): 5.0 +/- 3.1 UF, 3.6 +/- 3.5 continuous infusion, and 2.9 +/- 3.5 bolus diuretics (P = .001 UF versus bolus diuretic; P > .05 for the other comparisons). Net fluid loss (L): 4.6 +/- 2.6 UF, 3.9 +/- 2.7 continuous infusion, and 3.1 +/- 2.6 bolus diuretics (P < .001 UF versus bolus diuretic; P > .05 for the other comparisons). At 90 days, rehospitalizations plus unscheduled visits for HF/patient (rehospitalization equivalents) were fewer in UF group (0.65 +/- 1.36) than in continuous infusion (2.29 +/- 3.23; P = .016 versus UF) and bolus diuretics (1.31 +/- 1.87; P = .050 versus UF) groups. No serum creatinine differences occurred between groups up to 90 days. Conclusions: Despite similar fluid loss with UF and continuous diuretic infusion, fewer HF rehospitalizations equivalents occurred only with UF. Removal of isotonic fluid by UF compared with hypotonic urine by diuretics more effectively reduces total body sodium in congested HE patients. (J Cardiac Fail 2010;16:277-284) C1 [Costanzo, Maria Rosa] Midwest Heart Fdn, Lombard, IL USA. [Saltzberg, Mitchell T.] Univ Penn, Dept Med, Div Cardiol, Christiana Hosp, Philadelphia, PA 19104 USA. [Teerlink, John R.] Univ Calif San Francisco, Cardiol Sect, San Francisco Vet Affairs Med Ctr, Sch Med, San Francisco, CA 94143 USA. [Sobotka, Paul A.] Ohio State Univ, Affiliate Fac, Columbus, OH 43210 USA. RP Costanzo, MR (reprint author), Midwest Heart Fdn, Edward Heart Hosp, 4th Floor,801 S Washington St,POB 3226, Naperville, IL 60506 USA. EM mcostanzo@midwestheart.com RI Teerlink, John/D-2986-2012 NR 20 TC 56 Z9 63 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD APR PY 2010 VL 16 IS 4 BP 277 EP 284 DI 10.1016/j.cardfail.2009.12.009 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 588HR UT WOS:000277060400001 PM 20350693 ER PT J AU Martinelli, M De Siqueira, SF Costa, R Greco, OT Moreira, LF D'Avila, A Heist, EK AF Martinelli Filho, Martino De Siqueira, Sergio Freitas Costa, Roberto Greco, Oswaldo T. Moreira, Luiz Felipe D'Avila, Andre Heist, E. Kevin TI Conventional Versus Biventricular Pacing in Heart Failure and Bradyarrhythmia: The COMBAT Study SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Chronic conventional right ventricular pacing; cardiac resynchronization therapy; heart failure; AV block ID INTRAVENTRICULAR-CONDUCTION DELAY; BUNDLE-BRANCH-BLOCK; CARDIAC-RESYNCHRONIZATION; IMPLANTABLE DEFIBRILLATOR; DUAL-CHAMBER; STIMULATION; PACEMAKERS; RATIONALE; THERAPY; DESIGN AB Background: Worsening in clinical and cardiac status has been noted after chronic right ventricular pacing, but it is uncertain whether atriobiventricular (BiVP) is preferable to atrio-right ventricular pacing (RVP). Conventional versus Multisite Pacing for BradyArrhythmia Therapy study (COMBAT) sought to compare BiVP versus RVP in patients with symptomatic heart failure (HF) and atrioventricular (AV) block. Methods and Results: COMBAT is a prospective multicenter randomized double blind crossover study. Patients with New York Heart Association functional class (FC) II-IV, left ventricular ejection fraction (LVEF) <40%, and AV block as an indication for pacing were enrolled. All patients underwent biventricular system implantation and then were randomized to receive successively (group A) RVP-BiVP-RVP, or (group B) BiVP-RVP-BiVP. At the end of each 3-month crossover period, patients were evaluated according to Quality of Life (QoL), FC, echocardiographic parameters, 6-Minute Walk Test (6MWT), and peak oxygen consumption (VO(2max)). Sixty patients were enrolled, and the mean follow-up period was 17.5 +/- 10.7 months. There were significant improvements in QoL, FC, LVEF, and left ventricular end-systolic volume with BiVP compared with RVP. The effects of pacing mode on 6MWT and VO(2max) were not significantly different. Death occurred more frequently with RVP. Conclusion: In patients with systolic HF and AV block requiring permanent ventricular pacing, BiVP is superior to RVP and should be considered the preferred pacing mode. (J Cardiac Fail 2010;16:293-300) C1 [Martinelli Filho, Martino; De Siqueira, Sergio Freitas; Costa, Roberto; Moreira, Luiz Felipe] Univ Sao Paulo, Sch Med, Heart Inst InCor, Pacemaker Clin, BR-05508 Sao Paulo, Brazil. [Greco, Oswaldo T.] Hosp Base Sao Jose Rio Preto, Sao Paulo, Brazil. [D'Avila, Andre] Mt Sinai Hosp, Cardiac Arrhythmia Serv, New York, NY 10029 USA. [Heist, E. Kevin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. RP Martinelli, M (reprint author), In Cor HC FMUSP, Clin Marcapasso, Av Eneas Carvalho Aguiar 44, BR-05403000 Sao Paulo, Brazil. EM martino@incor.usp.br RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009; Siqueira, Sergio/E-4836-2012; Costa, Roberto/F-2682-2012; Martinelli, Martino/D-9785-2012; Moreira, Luiz Felipe/F-9882-2012 OI d'Avila, Andre Luiz/0000-0001-8769-1411; Costa, Roberto/0000-0001-6104-9113; Martinelli, Martino/0000-0003-4440-8078; FU Medtronic Comercial Ltd FX Medtronic Comercial Ltd supported this study. M.M.F.: Biotronik (research support, speaker), Medtronic (research support, speaker), St. Jude Medical (speaker). S.F.d.S.: Part-time St Jude Medical employee. R.C.: Biotronik (research support, speaker), Medtronic (research support, speaker), St. Jude Medical (speaker). O.T.G.: Medtronic (research support). A.d.'A.: Medtronic (consultant and speaker), Boston Scientific (speaker), St. Jude Medical (consultant, speaker and research support). KB.: Biotronik (speaker), Boston Scientific (research support, speaker), ELA/Sorin (speaker), Medtronic (speaker), St. Jude Medical (research support, speaker, consultant). NR 29 TC 14 Z9 14 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD APR PY 2010 VL 16 IS 4 BP 293 EP 300 DI 10.1016/j.cardfail.2009.12.008 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 588HR UT WOS:000277060400003 PM 20350695 ER PT J AU Blendea, D Heist, EK Das, S Danik, S Barrett, C Mela, T Ruskin, JN Singh, JP AF Blendea, Dan Heist, E. Kevin Das, Saumya Danik, Stephan Barrett, Conor Mela, Theofanie Ruskin, Jeremy N. Singh, Jagmeet P. TI Impact of Tricuspid Regurgitation and Prior Coronary Bypass Surgery on the Geometry of the Coronary Sinus: A Rotational Coronary Angiography Study SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE coronary venous anatomy; coronary sinus geometry; cardiac resynchronization therapy; heart failure; coronary artery bypass surgery ID CARDIAC RESYNCHRONIZATION THERAPY; CHRONIC HEART-FAILURE; MITRAL ANNULOPLASTY; COMPUTED-TOMOGRAPHY; ANATOMY; ANNULUS; VALVE AB Methods and Results: Seventy-nine patients undergoing RCVA for cardiac resynchronization therapy (CRT) were evaluated: age 63 +/- 15 years, 43% with prior coronary artery bypass grafting (CABG). Aspects of the CS anatomy which could impact cannulation were examined: the CS ostial angle, the posterior displacement of the CS away from the atrioventricular groove, a measure of CS curvature, and the presence of stenoses and aneurysmal dilatations. The CS ostial angle was variable (65-151 degrees, mean 119 +/- 19 degrees, < 90 degrees in 8 patients) and decreased significantly (P = 0.0022) with increasing severity of tricuspid regurgitation (TR), reaching 94 +/- 18 degrees in patients with severe TR. The posterior displacement of the CS was significantly more accentuated in patients with prior CABG when compared with the patients without CABG (7.1 +/- 3.7 vs 4.5 +/- 2.8 mm; P = 0.0246). The decrease in luminal diameter at the CS-great cardiac vein (GCV) junction was 2.0 +/- 1.0 mm, being more pronounced in patients with prior CABG versus nonCABG (26 vs 20%; P = 0.042). Stenoses and aneurysmal dilatations of the CS-GCV were encountered in 4 (5%) and 6 (8%) of patients, respectively, all of them with prior CABG, representing 12% and 18% of the CABG group. Conclusion: The CS anatomy in patients undergoing CRT is variable, and is impacted by the severity of the underlying TR and history of a prior CABG. (J Cardiovasc Electrophysiol, Vol. 21, pp. 436-440, April 2010). C1 [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiac Arrhythmia Serv,Dept Med, Ctr Heart,Cardiac Resynchronizat Therapy Program, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiac Arrhythmia Serv,Dept Med, Ctr Heart,Cardiac Resynchronizat Therapy Program, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org FU St. Jude Medical; Boston Scientific; Medtronic; Biotronik FX Dr. Heist has served as a consultant and received research grants from St. Jude Medical and Boston Scientific. Dr. Mela has received a grant from St. Jude Medical, grant and research support from Boston Scientific, and honoraria from Medtronic, St. Jude Medical, and Boston Scientific. Dr. Ruskin has served as consultant for Medtronic and Biosense Webster and received honorarium for faculty participation in Fellows programs from Boston Scientific and St. Jude Medical. Dr. Singh has served as a consultant and received research grants from Boston Scientific, St. Jude Medical, Medtronic, and Biotronik. Drs. Blendea, Das, Danik, and Barrett declare no potential conflicts of interest. NR 13 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD APR PY 2010 VL 21 IS 4 BP 436 EP 440 DI 10.1111/j.1540-8167.2009.01639.x PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575AM UT WOS:000276035400011 PM 19909387 ER PT J AU Yarbrough, WM Mukherjee, R Stroud, RE Meyer, EC Escobar, GP Sample, JA Hendrick, JW Mingoia, JT Spinale, FG AF Yarbrough, William M. Mukherjee, Rupak Stroud, Robert E. Meyer, Evan C. Escobar, G. Patricia Sample, Jeffrey A. Hendrick, Jennifer W. Mingoia, Joseph T. Spinale, Francis G. TI Caspase Inhibition Modulates Left Ventricular Remodeling Following Myocardial Infarction Through Cellular and Extracellular Mechanisms SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the Institute-of-Cardiovascular-Science-and-Medicine CY DEC 13, 2009 CL Hong Kong, PEOPLES R CHINA SP Inst Cardiovasc Sci & Med DE myocardial infarction; remodeling; caspase inhibition; left ventricular ID MATRIX-METALLOPROTEINASE INHIBITION; HEART-FAILURE; DNA FRAGMENTATION; RABBIT HEART; IN-VIVO; APOPTOSIS; ISCHEMIA; DEATH; SIZE; RECOVERY AB Background: Myocyte death occurs by necrosis and caspase-mediated apoptosis in myocardial infarction (MI). In vitro studies suggest caspase activation causes myocardial contractile protein degradation without inducing apoptosis. Thus, caspase activation may evoke left ventricular (LV) remodeling through independent processes post-MI. The effects of caspase activation on LV geometry post-MI remain unclear. This project applied pharmacologic caspase inhibition (CASPI) to a porcine model of MI. Methods and Results: Pigs (34 kg) were instrumented to induce 60 minutes of coronary artery occlusion followed by reperfusion and a 7-day follow-up period. Upon reperfusion, the pigs were randomized to saline (n = 12) or CASPI (n = 10, IDN6734, 6 mg/kg IV, then 6 mg/kg/h for 24 hours). Plasma troponin-I values were reduced with CASPI compared with saline at 24 hours post-MI (133 +/- 15 vs. 189 +/- 20 ng/mL, respectively, P < 0.05). LV end-diastolic area (echocardiography) and interregional length (sonomicrometry) increased from baseline in both groups but were attenuated with CASPI by 40% and 90%, respectively (P < 0.05). Myocyte length was reduced with CASPI compared with saline (128 +/- 3 vs. 141 +/- 4 mm, respectively, P < 0.05). Plasma-free pro-matrix metalloproteinase-2 values increased from baseline with CASPI (27% +/- 6%, P < 0.05) indicative of reduced conversion to active MMP-2. Separate in vitro studies demonstrated that activated caspase species cleaved pro-MMP-2 yielding active MMP-2 forms and that MMP activity was increased in the presence of activated caspase-3. Conclusions: CASPI attenuated regional and global LV remodeling post-MI and altered viable myocyte geometry. Caspases increased MMP activity in vitro, whereas CASPI modified conversion of MMP-2 to the active form in vivo. Taken together, the results of the present study suggest that the elaboration of caspases post-MI likely contribute to LV remodeling through both cellular and extracellular mechanisms. C1 [Yarbrough, William M.; Mukherjee, Rupak; Stroud, Robert E.; Meyer, Evan C.; Escobar, G. Patricia; Sample, Jeffrey A.; Hendrick, Jennifer W.; Mingoia, Joseph T.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Yarbrough, William M.; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, 770 MUSC Complex,STRB,Suite 625, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU NHLBI NIH HHS [HL-81692, HL-07260, HL-87134, R01 HL057952, R01 HL057952-12, R01 HL059165, R01 HL059165-12, T32 HL007260] NR 30 TC 11 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD APR PY 2010 VL 55 IS 4 BP 408 EP 416 DI 10.1097/FJC.0b013e3181d4ca66 PG 9 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 591NN UT WOS:000277307900014 PM 20147844 ER PT J AU Hayakawa, K Nakano, T Irie, K Higuchi, S Fujioka, M Orito, K Iwasaki, K Jin, G Lo, EH Mishima, K Fujiwara, M AF Hayakawa, Kazuhide Nakano, Takafumi Irie, Keiichi Higuchi, Sei Fujioka, Masayuki Orito, Kensuke Iwasaki, Katsunori Jin, Guang Lo, Eng H. Mishima, Kenichi Fujiwara, Michihiro TI Inhibition of reactive astrocytes with fluorocitrate retards neurovascular remodeling and recovery after focal cerebral ischemia in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE angiogenesis; astrocytes; cerebral ischemia; high-mobility group box 1; neuroplasticity; neuroprotection ID GROUP BOX1-INHIBITING MECHANISM; CENTRAL-NERVOUS-SYSTEM; CANNABIDIOL PREVENTS; BRAIN ISCHEMIA; GLIAL SCAR; RAT-BRAIN; INJURY; ANGIOGENESIS; REGENERATION; METABOLISM AB Glial scarring is traditionally thought to be detrimental after stroke. But emerging studies now suggest that reactive astrocytes may also contribute to neurovascular remodeling. Here, we assessed the effects and mechanisms of metabolic inhibition of reactive astrocytes in a mouse model of stroke recovery. Five days after stroke onset, astrocytes were metabolically inhibited with fluorocitrate (FC, 1 nmol). Markers of reactive astrocytes (glial fibrillary acidic protein (GFAP), HMGB1), markers of neurovascular remodeling (CD31, synaptophysin, PSD95), and behavioral outcomes (neuroscore, rotarod latency) were quantified from 1 to 14 days. As expected, focal cerebral ischemia induced significant neurological deficits in mice. But over the course of 14 days after stroke onset, a steady improvement in neuroscore and rotarod latencies were observed as the mice spontaneously recovered. Reactive astrocytes coexpressing GFAP and HMGB1 increased in peri-infarct cortex from 1 to 14 days after cerebral ischemia in parallel with an increase in the neurovascular remodeling markers CD31, synaptophysin, and PSD95. Compared with stroke-only controls, FC-treated mice demonstrated a significant decrease in HMGB1-positive reactive astrocytes and neurovascular remodeling, as well as a corresponding worsening of behavioral recovery. Our results suggest that reactive astrocytes in peri-infarct cortex may promote neurovascular remodeling, and these glial responses may aid functional recovery after stroke. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 871-882; doi:10.1038/jcbfm.2009.257; published online 9 December 2009 C1 [Hayakawa, Kazuhide; Nakano, Takafumi; Irie, Keiichi; Higuchi, Sei; Fujioka, Masayuki; Iwasaki, Katsunori; Mishima, Kenichi; Fujiwara, Michihiro] Fukuoka Univ, Fac Pharmaceut Sci, Dept Neuropharmacol, Fukuoka 8140180, Japan. [Hayakawa, Kazuhide; Jin, Guang; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA. [Hayakawa, Kazuhide; Jin, Guang; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA. [Orito, Kensuke] Azabu Univ, Dept Pharmacol, Sch Vet Med, Kanagawa, Japan. [Iwasaki, Katsunori; Mishima, Kenichi] Fukuoka Univ, Adv Mat Inst, Fukuoka 8140180, Japan. RP Mishima, K (reprint author), Fukuoka Univ, Fac Pharmaceut Sci, Dept Neuropharmacol, 8-19-1 Nanakuma, Fukuoka 8140180, Japan. EM kenichi@fukuoka-u.ac.jp FU Ministry of Education, Science and Culture of Japan [20590552]; Advanced Materials Institute of Fukuoka University; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Japan Society for the Promotion of Science; NIH [R37-NS37074, P01-NS55104]; American Heart Association FX This study was supported in part by a Grant-in-Aid for Scientific Research (no. 20590552) from the Ministry of Education, Science and Culture of Japan, the Advanced Materials Institute of Fukuoka University, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, a Postdoctoral Fellowship for Research Abroad from the Japan Society for the Promotion of Science, and NIH Grants R37-NS37074, P01-NS55104, and a Bugher award from the American Heart Association. NR 40 TC 52 Z9 55 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2010 VL 30 IS 4 BP 871 EP 882 DI 10.1038/jcbfm.2009.257 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 577BZ UT WOS:000276197200022 PM 19997116 ER PT J AU Mishra, SK Singh, P AF Mishra, Shri Kant Singh, Parampreet TI History of Neuroimaging: The Legacy of William Oldendorf SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE history of neurology; neuroimaging; CT scan; Nobel Prize; neuroradiology ID BRAIN-BARRIER PERMEABILITY; KETONE-BODIES; STARVATION; PHYSIOLOGY; TRANSPORT; HEXOSES AB The field of neuroimaging witnessed remarkable progress in the post-World War II era, resulting in tremendous benefits for healthcare today. One such important milestone was the development of the computerized axial tomography (CAT) scan. This state of the art technique has paved the way for modern diagnostic imaging like magnetic resonance imaging (MRI). Dr William Oldendorf, the first designer of axial tomography, is regarded by some as the true father of neuroimaging. However, because of various reasons, he was unable to succeed with his concept and was also unfortunately denied his due entitlement of the Nobel Prize for Medicine and Physiology in 1979. This article discusses his contributions to the fields of neuroimaging and neurosciences, along with the politics that surrounded the awarding of the Nobel Prize of 1979. Another associated topic that is touched on in this article is the ever-growing dispute over the interpretations of neuroimaging between neurologists and neuroradiologists. C1 [Mishra, Shri Kant] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Mishra, Shri Kant] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Mishra, Shri Kant] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Mishra, Shri Kant; Singh, Parampreet] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. RP Mishra, SK (reprint author), 16111 Plummer St, Sepulveda, CA 91343 USA. EM smishra@usc.edu NR 23 TC 1 Z9 1 U1 0 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD APR PY 2010 VL 25 IS 4 BP 508 EP 517 DI 10.1177/0883073809359083 PG 10 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 579HU UT WOS:000276360400019 PM 20382954 ER PT J AU Gagnon, DR McLean, RR Hannan, MT Cupples, LA Hogan, M Kiel, DP AF Gagnon, David R. McLean, Robert R. Hannan, Marian T. Cupples, L. Adrienne Hogan, Mary Kiel, Douglas P. TI Cross-Calibration and Comparison of Variability in 2 Bone Densitometers in a Research Setting: The Framingham Experience SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE Bone; mineral density; cross-calibration; dual x-ray absorptiometry ID X-RAY ABSORPTIOMETRY; LEAST SIGNIFICANT CHANGE; DXA SYSTEMS; OSTEOPOROSIS AB New technology introduced over time results in changes in densitometers during longitudinal studies of bone mineral density (BMD). This requires that a cross-calibration process be completed to translate measurements from the old densitometer to the new one. Previously described cross-calibration methods for research settings have collected single measures on each densitometer and used linear regression to estimate cross-calibration corrections. Thus, these methods may produce corrections that have limited precision and underestimate the variability in converted BMD values. Furthermore, most of the previous studies have included small samples recruited from specialized populations. Increasing the sample size, obtaining multiple measures on each machine, and using linear mixed models to account for between- and within-subject variability may improve cross-calibration estimates. The purpose of this study was to conduct an in vivo cross-calibration of a Lunar DPX-L (Lunar Corporation, Madison, WI) with a Lunar Prodigy densitometer (GE Medical Systems Lunar, Madison, WI) using a sample of 249 healthy volunteers who were scanned twice on each densitometer, without repositioning, at both the femur and spine. Scans were analyzed using both automated and manual placement of regions of interest. Wilcoxon rank-sum tests and Bland-Altman plots were used to examine possible differences between repeat scans within and across densitometers. We used linear mixed models to determine the cross-calibration equations for the femoral neck, trochanter, total hip, and lumbar spine (L2-L4) regions. Results using automated and manual placement of the regions of interest did not differ significantly. The DPX-L densitometer exhibited larger median absolute differences in the BMD values by repeat scans of femoral neck (0.016 vs 0.012, p = 0.1) and trochanter (0.011 vs. 0.009, p = 0.06) compared with the Prodigy densitometer. The Bland-Altman plots revealed no statistically significant linear relationship between the differences in paired measures between machines and mean BMD. In our large sample of healthy volunteers, we did detect systematic differences between the DPX-L and Prodigy densitometers. Our proposed cross-calibration method, which includes acquiring multiple measures and using linear mixed models, provides researchers with a more realistic estimate of the variance of cross-calibrated BMD measures, potentially reducing the chance of making a type I error in longitudinal studies of changes in BMD. C1 [McLean, Robert R.; Hannan, Marian T.; Hogan, Mary; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. [Gagnon, David R.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gagnon, David R.] Massachusetts Vet Epidemiol Res & Informat Ctr, MAVERIC, VA Cooperat Studies Program, Boston, MA USA. [McLean, Robert R.; Hannan, Marian T.; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA. [Hannan, Marian T.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Kiel, DP (reprint author), Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM kiel@hrca.harvard.edu OI Gagnon, David/0000-0002-6367-3179; Cupples, L. Adrienne/0000-0003-0273-7965; Hannan, Marian/0000-0002-9586-6928; Kiel, Douglas/0000-0001-8474-0310 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging [AR/AG41398]; American College of Rheumatology Research and Education Foundation FX Support for this work was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging (AR/AG41398), and by the American College of Rheumatology Research and Education Foundation Health Professional New Investigator Award to Dr. McLean. NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1094-6950 EI 1559-0747 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD APR-JUN PY 2010 VL 13 IS 2 BP 210 EP 218 DI 10.1016/j.jocd.2010.01.003 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 595HF UT WOS:000277600600010 PM 20347371 ER PT J AU Smith, RJ Nathan, DM Arslanian, SA Groop, L Rizza, RA Rotter, JI AF Smith, Robert J. Nathan, David M. Arslanian, Silva A. Groop, Leif Rizza, Robert A. Rotter, Jerome I. TI Individualizing Therapies in Type 2 Diabetes Mellitus Based on Patient Characteristics: What We Know and What We Need to Know SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BLOOD-GLUCOSE CONTROL; INSULIN-RESISTANCE; MOLECULAR-GENETICS; GLYCEMIC CONTROL; RISK-FACTORS; COMPLICATIONS; SULFONYLUREAS; SECRETION; METFORMIN; UKPDS AB Objective: Type 2 diabetes is heterogeneous in its clinical features, pathogenesis, and predisposing or causal genetic factors. This report examines what is known and what needs to be learned about the potential to individualize glycemic therapies in type 2 diabetes, based on phenotypes and genotypes. Participants: A 29-member international working group with expertise in diabetes epidemiology, physiology, genetics, clinical trials, and clinical care participated in formal presentations and discussions at a conference on April 16-17, 2009. A writing group subsequently prepared this summary and recommendations. The conference was coendorsed by The Endocrine Society and the American Diabetes Association and was supported by an unrestricted educational grant from Novo Nordisk. Evidence: Participants reviewed and discussed published literature, plus their own unpublished data. Consensus Process: The summary and recommendations were supported unanimously by the writing group as representing the majority or unanimous opinions of the working group. Conclusions: Recent advances in genetics, such as the identification of Kir6.2 mutations and the responsible genes for several forms of maturity onset diabetes of the young (MODY), have established precedents linking specifically effective therapies to defined diabetes subtypes. The recent increase in identified polygenic factors related to type 2 diabetes and our understanding of the pathogenesis of diabetes provide potential opportunities to individualize therapy. To further this process, we recommend expanded analysis of existing data sources and the development of new basic and clinical research studies, including a greater focus on identifying type 2 diabetes subtypes, their response to different therapies, and quantitation of cost-effectiveness. (J Clin Endocrinol Metab 95: 1566-1574, 2010) C1 [Smith, Robert J.] Brown Univ, Alpert Med Sch, Div Endocrinol, Providence, RI 02903 USA. [Smith, Robert J.] Brown Univ, Alpert Med Sch, Hallett Ctr Diabet & Endocrinol, Providence, RI 02903 USA. [Nathan, David M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arslanian, Silva A.] Univ Pittsburgh, Sch Med, Childrens Hosp, Pittsburgh, PA 15213 USA. [Groop, Leif] Lund Univ, S-20502 Malmo, Sweden. [Rizza, Robert A.] Mayo Clin, Rochester, MN 55905 USA. [Rotter, Jerome I.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Smith, RJ (reprint author), Hallett Ctr, 1 Hoppin St,Suite 200, Providence, RI 02903 USA. EM Robert_J_Smith@brown.edu FU The Endocrine Society; American Diabetes Association; Novo Nordisk FX This paper is based on a conference jointly sponsored by The Endocrine Society and the American Diabetes Association, with the financial support of an unrestricted educational grant to The Endocrine Society from Novo Nordisk. NR 42 TC 48 Z9 51 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2010 VL 95 IS 4 BP 1566 EP 1574 DI 10.1210/jc.2009-1966 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579UT UT WOS:000276402300011 PM 20194712 ER PT J AU Finkelstein, JS Wyland, JJ Lee, H Neer, RM AF Finkelstein, Joel S. Wyland, Jason J. Lee, Hang Neer, Robert M. TI Effects of Teriparatide, Alendronate, or Both in Women with Postmenopausal Osteoporosis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; GROWTH-FACTOR-I; HUMAN PARATHYROID HORMONE-(1-34); OVARIECTOMIZED RATS; VERTEBRAL FRACTURES; ESTROGEN DEFICIENCY; ANABOLIC RESPONSE; RANDOMIZED-TRIAL; THERAPY; MEN AB Context: Teriparatide increases both bone formation and bone resorption. Objective: We sought to determine whether combining teriparatide with an antiresorptive agent would alter its anabolic action. Design and Setting: This was a randomized controlled trial conducted in a single university hospital. Patients and Intervention: We randomized 93 postmenopausal women with low bone mineral density (BMD) to alendronate 10 mg daily (group 1), teriparatide 40 mu g sc daily (group 2), or both (group 3) for 30 months. Teriparatide was begun at month 6. Main Outcome Measures: BMD of the lumbar spine, proximal femur, proximal radius, and total body was measured by dual-energy x-ray absorptiometry (DXA) every 6 months. Lumbar spine trabecular BMD was measured at baseline and month 30 by quantitative computed tomography. Serum osteocalcin, N-terminal propeptide of type 1 collagen, and N-telopeptide levels were assessed frequently. Women who had at least one repeat DXA scan on therapy were included in the analyses (n = 69). Results: DXA spine BMD increased more in women treated with teriparatide alone than with alendronate alone (18 +/- 11 vs. 7 +/- 4%; P < 0.001) or both (18 +/- 11 vs. 12 +/- 9%; P = 0.045). Similarly, femoral neck BMD increased more in women treated with teriparatide alone than with alendronate alone (11 +/- 5 vs. 4 +/- 4%; P < 0.001) or both (11 +/- 5 vs. 3 +/- 5%; P < 0.001). Quantitative computed tomography spine BMD increased 1 +/- 7, 61 +/- 31, and 24 +/- 24% in groups 1, 2, and 3 (P < 0.001 for all comparisons). Serum osteocalcin, N-terminal propeptide of type 1 collagen, and cross-linked N-telopeptides of type I collagen increased more with teriparatide alone than with both (P < 0.001 for each marker). Conclusion: Alendronate reduces the ability of teriparatide to increase BMD and bone turnover in women. (J Clin Endocrinol Metab 95: 1838-1845, 2010) C1 [Finkelstein, Joel S.; Wyland, Jason J.; Neer, Robert M.] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM jfinkelstein@partners.org FU National Institutes of Health [5 P50 AR44855, K24 DK02759, RR-1066] FX This work was supported by National Institutes of Health Grants 5 P50 AR44855, K24 DK02759, and RR-1066. NR 43 TC 90 Z9 97 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2010 VL 95 IS 4 BP 1838 EP 1845 DI 10.1210/jc.2009-1703 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579UT UT WOS:000276402300043 PM 20164296 ER PT J AU Naour, N Rouault, C Fellahi, S Lavoie, ME Poitou, C Keophiphath, M Eberle, D Shoelson, S Rizkalla, S Bastard, JP Rabasa-Lhoret, R Clement, K Guerre-Millo, M AF Naour, Nadia Rouault, Christine Fellahi, Soraya Lavoie, Marie-Eve Poitou, Christine Keophiphath, Mayoura Eberle, Delphine Shoelson, Steve Rizkalla, Salwa Bastard, Jean-Philippe Rabasa-Lhoret, Remi Clement, Karine Guerre-Millo, Michele TI Cathepsins in Human Obesity: Changes in Energy Balance Predominantly Affect Cathepsin S in Adipose Tissue and in Circulation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INDUCED WEIGHT-LOSS; CYSTEINE PROTEASES; REDUCES ATHEROSCLEROSIS; MACROPHAGE INFILTRATION; DEFICIENT MICE; CYSTATIN C; EXPRESSION; DIFFERENTIATION; ADIPOGENESIS; ACCUMULATION AB Context: Recent studies in humans and mice suggest the implication of the cysteine proteases cathepsins S, L, and K in vascular and metabolic complications of obesity. Objective: Our objective was to identify clinically relevant forms of cathepsin in human obesity. Design and Setting: We conducted a prospective study on two independent cohorts. Participants and Interventions: The first cohort includes 45 obese women eligible for gastric surgery (age, 39 +/- 1.6 yr; body mass index, 47 +/- 0.99 kg/m(2)) and 17 nonobese women (age, 38 +/- 1.8 yr; body massindex, 21 +/- 0.44 kg/m(2)). The second cohort comprises 29 obese women(age, 57 +/- 0.8 yr; body mass index, 34 +/- 0.69 kg/m2) undergoing 6 months of medically supervised caloric restriction. Main Outcomes: Cathepsin S, L, and K mRNA levels were determined in surgical adipose tissue biopsies. The proteins were measured in conditioned medium of adipose tissue explants and in circulation. Results: Obese subjects had a 2-fold increase in cathepsin S mRNA in adipose tissue as compared with normal-weight subjects and an increased rate (1.5-fold) of cathepsin S release in adipose tissue explants. Cathepsin S circulating concentrations were increased with obesity (+30%) and reduced after weight reduction (P < 0.05 for both). By contrast, cathepsin L was unaffected in adipose tissue and serum; cathepsin K was undetectable in circulation and unchanged in adipose tissue. Conclusion: In humans, cathepsin S is more influenced than cathepsins L and K by changes in energy balance in adipose tissue and circulation. This opens new avenues to explore whether selective inhibition of this protease could reduce cardiovascular risk and ameliorate metabolic status in obese subjects. (J Clin Endocrinol Metab 95: 1861-1868, 2010) C1 [Naour, Nadia; Rouault, Christine; Poitou, Christine; Keophiphath, Mayoura; Rizkalla, Salwa; Clement, Karine; Guerre-Millo, Michele] Univ Paris 06, Ctr Rech Cordeliers, INSERM, U872,UMR S 872, F-75006 Paris, France. [Naour, Nadia; Rouault, Christine; Poitou, Christine; Keophiphath, Mayoura; Rizkalla, Salwa; Clement, Karine] Univ Paris 05, UMR S 872, F-75006 Paris, France. [Fellahi, Soraya; Bastard, Jean-Philippe] Tenon Hosp, Dept Biochem & Hormonol, AP HP, F-75020 Paris, France. [Fellahi, Soraya; Bastard, Jean-Philippe] INSERM, U680, F-75006 Paris, France. [Lavoie, Marie-Eve; Rabasa-Lhoret, Remi] Univ Montreal, Dept Nutr, Montreal, PQ H3C 1C5, Canada. [Lavoie, Marie-Eve; Rabasa-Lhoret, Remi] Clin Res Inst Montreal, Montreal, PQ H3A 2B4, Canada. [Poitou, Christine; Rizkalla, Salwa; Clement, Karine] Hop La Pitie Salpetriere, AP HP, Dept Nutr & Endocrinol, F-75013 Paris, France. [Poitou, Christine; Rizkalla, Salwa; Clement, Karine] Ctr Res Human Nutr Ile France, F-75013 Paris, France. [Eberle, Delphine; Shoelson, Steve] Joslin Diabet Ctr, Boston, MA USA. [Rabasa-Lhoret, Remi] Univ Hosp, Res Ctr, Montreal Diabet Res Ctr, Montreal, PQ H3H 2R9, Canada. RP Guerre-Millo, M (reprint author), Ctr Rech Cordeliers, INSERM, U872, Eq7, 15 Rue Ecole Med, F-75007 Paris, France. EM michele.guerre-millo@crc.jussieu.fr FU Fondation pour la Recherche Medicale; Program Hospitalier de Recherche Clinique; Assistance Publique des Hopitaux de Paris [AOR02076]; French National Agency of Research (OBCAT) [ANR-05-PCOD-026-01]; DANONE/Fondation pour la Recherche Medicale; Commission of the European Communities [HEALTH-F262008-201100] FX This work was supported by the Fondation pour la Recherche Medicale to N. N., a Program Hospitalier de Recherche Clinique, Assistance Publique des Hopitaux de Paris(AOR02076), a grant from the French National Agency of Research (OBCAT, program ANR-05-PCOD-026-01), a prize DANONE/Fondation pour la Recherche Medicale to K. C., and the Commission of the European Communities (Collaborative Project ADAPT, contract number HEALTH-F262008-201100). NR 32 TC 34 Z9 34 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2010 VL 95 IS 4 BP 1861 EP 1868 DI 10.1210/jc.2009-1894 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579UT UT WOS:000276402300047 PM 20164293 ER PT J AU Shaw, ND Histed, SN Srouji, SS Yang, J Lee, H Hall, JE AF Shaw, N. D. Histed, S. N. Srouji, S. S. Yang, J. Lee, H. Hall, J. E. TI Estrogen Negative Feedback on Gonadotropin Secretion: Evidence for a Direct Pituitary Effect in Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; POSTMENOPAUSAL WOMEN; GONADAL-STEROIDS; FEMALE RATS; OVARIECTOMIZED EWE; POSITIVE FEEDBACK; GENE-EXPRESSION; LH-RELEASE; PROGESTERONE AB Context: Studies in humans and animals indicate that estrogen negative feedback occurs at the level of the hypothalamus, but it is unclear whether estrogen also exerts an inhibitory effect directly at the pituitary. Objectives: The aim of the study was to determine whether estrogen has a direct negative feedback effect at the pituitary and whether this varies with aging. Design and Setting: A GnRH antagonist and graded doses of GnRH were used to isolate pituitary responsiveness before and after estrogen administration in Clinical Research Center studies at an academic medical center. Subjects: Subjects were healthy postmenopausal women aged 48-56 yr (n = 8) or 70-75 yr (n = 8). Interventions: A suppressive dose of the NAL-GLU GnRH antagonist was administered, followed by graded doses of GnRH before and after 1 month of estrogen administration. Results: LH and FSH responses to GnRH decreased after estrogen administration (P = 0.01 and P = 0.0001, respectively). The ratio of FSH to LH amplitudes decreased in response to estrogen (P = 0.04) indicating a greater sensitivity of FSH than LH to inhibition by estrogen. The inhibitory effect of estrogen on FSH was attenuated with aging (P = 0.02), but was maintained for LH (P = 0.4). Conclusions: Studies that control for endogenous GnRH and estradiol demonstrate a direct pituitary site of estrogen negative feedback on LH and FSH responsiveness to GnRH in women. The effect of estrogen on FSH responsiveness is greater than on LH and is attenuated with aging. These studies indicate that estrogen negative feedback occurs directly at the pituitary and contributes to the differential regulation of FSH and LH secretion. (J Clin Endocrinol Metab 95: 1955-1961, 2010) C1 [Hall, J. E.] Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 5, Dept Med, Boston, MA 02114 USA. [Yang, J.; Lee, H.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Shaw, N. D.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 5, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org OI Shaw, Natalie/0000-0002-0847-9170 FU National Institutes of Health (NIH) [R01 AG13241, M01 RR01066, 5T32 HD007396]; Berlex Laboratories, Inc. FX This work was supported by National Institutes of Health (NIH) Grants R01 AG13241 and M01 RR01066. N.D.S. received fellowship support from the NIH (5T32 HD007396). Product donation was received from Berlex Laboratories, Inc. NR 47 TC 26 Z9 26 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2010 VL 95 IS 4 BP 1955 EP 1961 DI 10.1210/jc.2009-2108 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579UT UT WOS:000276402300058 PM 20133465 ER PT J AU Rubin, MF Brunelli, SM Townsend, RR AF Rubin, Mario F. Brunelli, Stephen M. Townsend, Raymond R. TI Variability-The Drama of the Circulation SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material ID BLOOD-PRESSURE VARIABILITY; HEART-RATE-VARIABILITY; DIABETIC AUTONOMIC NEUROPATHY; STAGE RENAL-DISEASE; PROGNOSTIC VALUE; RISK-FACTOR; MORTALITY; ASSOCIATION; RATS; ATHEROSCLEROSIS AB The two most common vital signs, ie, pulse and blood pressure (BP), are obtained to seek guidance in clinical management of patients in virtually all primary care practices. Even a cursory glance at their values, whether it is within a person over time or between patients on a particular day, reflects an amazing degree of variability. In this brief editorial we provide a focused review of the assessment and the importance of variability in within-patient heart rate and BP and conclude with a few thoughts about the discordance in significance attached to these ubiquitous clinical measures. C1 [Townsend, Raymond R.] Univ Penn, Dept Med, Div Renal, Philadelphia, PA 19104 USA. [Brunelli, Stephen M.] Harvard Univ, Sch Med, Boston, MA USA. [Brunelli, Stephen M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Rubin, Mario F.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Townsend, RR (reprint author), Univ Penn, Dept Med, Div Renal, 3400 Spruce St,122 Founders Bldg, Philadelphia, PA 19104 USA. EM townsend@mail.med.upenn.edu NR 30 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD APR PY 2010 VL 12 IS 4 BP 284 EP 287 DI 10.1111/j.1751-7176.2009.00262.x PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 579GE UT WOS:000276356000008 PM 20433549 ER PT J AU Ren, B Deng, Y Mukhopadhyay, A Lanahan, AA Zhuang, ZW Moodie, KL Mulligan-Kehoe, MJ Byzova, TV Peterson, RT Simons, M AF Ren, Bin Deng, Yong Mukhopadhyay, Arpita Lanahan, Anthony A. Zhuang, Zhen W. Moodie, Karen L. Mulligan-Kehoe, Mary Jo Byzova, Tatiana V. Peterson, Randall T. Simons, Michael TI ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ENDOTHELIAL-GROWTH-FACTOR; CYTOPLASMIC DOMAIN; CELL-MIGRATION; IN-VIVO; VEGF; ANGIOGENESIS; PROTEIN; EXPRESSION; KINASE; NEUROPILIN-1 AB Arterial morphogenesis is an important and poorly understood process. In particular, the signaling events controlling arterial formation have not been established. We evaluated whether alterations in the balance between ERK1/2 and PI3K signaling pathways could stimulate arterial formation in the setting of defective arterial morphogenesis in mice and zebrafish. Increased ERK1/2 activity in mouse ECs with reduced VEGF responsiveness was achieved in vitro and in vivo by downregulating PI3K activity, suppressing Aka but not Akt2 expression, or introducing a constitutively active ERK1/2 construct. Such restoration of ERK1/2 activation was sufficient to restore impaired arterial development and branching morphogenesis in synectin-deficient mice and synectin-knockdown zebrafish. The same approach effectively stimulated arterial growth in adult mice, restoring arteriogenesis in mice lacking synectin and in atherosclerotic mice lacking both LDL-R and ApoB48. We therefore conclude that PI3K-ERK1/2 crosstalk plays a key role in the regulation of arterial growth and that the augmentation of ERK signaling via suppression of the PI3K signaling pathway can effectively stimulate arteriogenesis. C1 [Deng, Yong; Lanahan, Anthony A.; Zhuang, Zhen W.; Simons, Michael] Yale Univ, Sch Med, Sect Cardiovasc Med, Dept Internal Med, New Haven, CT 06520 USA. [Ren, Bin] Cleveland Clin Fdn, Dept Cell Biol, Cleveland, OH USA. [Mukhopadhyay, Arpita; Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Moodie, Karen L.; Mulligan-Kehoe, Mary Jo] Dartmouth Med Sch, Dept Med, Lebanon, NH USA. [Byzova, Tatiana V.] Cleveland Clin Fdn, Dept Mol Cardiol, Cleveland, OH USA. [Simons, Michael] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA. RP Simons, M (reprint author), Yale Univ, Sch Med, Sect Cardiovasc Med, Dept Internal Med, 333 Cedar St,POB 208017, New Haven, CT 06520 USA. EM michael.simons@yale.edu RI Simons, Michael/G-8553-2014 OI Simons, Michael/0000-0003-0348-7734 FU NIH [HL84619, HL53793, HL079267, HL69948] FX This work was supported in part by NIH grants HL84619 and HL53793 (to M. Simons), HL079267 (to R.T. Peterson), and HL69948 (to Mi. Mulligan-Kehoe). NR 48 TC 57 Z9 59 U1 0 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2010 VL 120 IS 4 BP 1217 EP 1228 DI 10.1172/JCI39837 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 577XU UT WOS:000276258100031 PM 20237411 ER PT J AU Yi, W Seth, NP Martillotti, T Wucherpfennig, KW Sant'Angelo, DB Denzin, LK AF Yi, Woelsung Seth, Nilufer P. Martillotti, Tom Wucherpfennig, Kai W. Sant'Angelo, Derek B. Denzin, Lisa K. TI Targeted regulation of self-peptide presentation prevents type I diabetes in mice without disrupting general immunocompetence SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CD4 T-CELLS; HLA-DO; ANTIGEN PRESENTATION; DENDRITIC CELLS; INVARIANT CHAIN; B-CELLS; CENTRAL TOLERANCE; NOD MOUSE; EXPRESSION; DM AB Peptide loading of MHC class II (MHCII) molecules is directly catalyzed by the MHCII-like molecule HLA-DM (DM). Another MHCII-like molecule, HLA-DO (DO), associates with DM, thereby modulating DM function. The biological role of DO-mediated regulation of DM activity in vivo remains unknown; however, it has been postulated that DO expression dampens presentation of self antigens, thereby preventing inappropriate T cell activation that ultimately leads to autoimmunity. To test the idea that DO modulation of the MHCII self-peptide repertoire mediates self tolerance, we generated NOD mice that constitutively overexpressed DO in DCs (referred to herein as NOD.DO mice). NOD mice are a mouse model for type 1 diabetes, an autoinunune disease mediated by the destruction of insulin-secreting pancreatic beta cells. Our studies showed that diabetes development was completely blocked in NOD.DO mice. Similar to NOD mice, NOD.DO animals selected a diabetogenic T cell repertoire, and the numbers and function of Tregs were normal. Indeed, immune system function in NOD.DO mice was equivalent to that in NOD mice. NOD.DO DCs, however, presented an altered, MHCII-bound self-peptide repertoire, thereby preventing the activation of diabetogenic T cells and subsequent diabetes development. These studies show that DO expression can shape the overall MHCII self-peptide repertoire to promote T cell tolerance. C1 [Yi, Woelsung; Martillotti, Tom; Sant'Angelo, Derek B.; Denzin, Lisa K.] Mem Sloan Kettering Canc Ctr, Program Immunol, Sloan Kettering Inst, New York, NY 10065 USA. [Seth, Nilufer P.; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Seth, Nilufer P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. [Sant'Angelo, Derek B.; Denzin, Lisa K.] Cornell Univ, Weill Grad Sch Med Sci, New York, NY 10021 USA. [Sant'Angelo, Derek B.; Denzin, Lisa K.] Louis V Gerstner Jr Grad Sch Biomed Sci, New York, NY USA. RP Denzin, LK (reprint author), Mem Sloan Kettering Canc Ctr, Program Immunol, Sloan Kettering Inst, 1275 York Ave,Box 509, New York, NY 10065 USA. EM denzinl@mskcc.org FU Juvenile Diabetes Research Foundation [5-2007-576]; NIH [RO1-A1061484]; JDRF Center on Immunological Tolerance [4-2007-1057] FX We thank Teresa Di Lorenzo, Mark Chong, Susan Wong, and members of the Denzin, Sant'Angelo, and Chaudhuri laboratories for helpful advice; Luis Ferran and H. Maggie O'Rourke for expert animal care; and Ming Li and Nicole Draghi for critical reading of the manuscript. This project was funded by a Juvenile Diabetes Research Foundation Innovative Research grant (5-2007-576) and NIH grant RO1-A1061484 to L.K. Denzin and by a JDRF Center on Immunological Tolerance in T1D at HMS grant (4-2007-1057; PI Diane Mathis) to K.W. Wucherpfennig. NR 55 TC 36 Z9 36 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2010 VL 120 IS 4 BP 1324 EP 1336 DI 10.1172/JCI40220 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 577XU UT WOS:000276258100040 PM 20200448 ER PT J AU Koo, S Bryar, JM Baden, LR Marty, FM AF Koo, Sophia Bryar, Julie M. Baden, Lindsey R. Marty, Francisco M. TI Prognostic Features of Galactomannan Antigenemia in Galactomannan-Positive Invasive Aspergillosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; CELL TRANSPLANT RECIPIENTS; MYCOSES STUDY-GROUP; PULMONARY ASPERGILLOSIS; ENZYME-IMMUNOASSAY; CIRCULATING GALACTOMANNAN; EUROPEAN-ORGANIZATION; NEUTROPENIC PATIENTS; SERUM GALACTOMANNAN; ANTIFUNGAL THERAPY AB Prognostic features of serum galactomannan (GM) remain poorly defined in patients with GM-positive invasive aspergillosis (GPA). We identified 93 patients with proven or probable invasive aspergillosis (IA) and GM values of >= 0.50 from January 2005 to March 2009. We used Cox modeling of time to 6- and 12-week mortality for the GM level at the time of diagnosis (GM(0)), GM decay in the week following diagnosis in 72 patients with >= 2 GM values, other predictors of mortality, and antifungal use during the week following diagnosis. Six-week mortality was 55% in the whole cohort and 43% in patients with >= 2 GM determinations. The hazard ratio (HR) of GM(0) per unit increase and 1-week GM decay per unit decline per week were 1.25 (95% confidence interval [CI], 1.01 to 1.54; P = 0.04) and 0.78 (95% CI, 0.63 to 0.96; P = 0.02), respectively, adjusting for other predictors of IA mortality; these values remained stable after adjusting for antifungal use and were predictive of all-cause mortality at 12 weeks with similar adjusted HR values. We conclude that the combination of GM(0) and 1-week GM decay is predictive of all-cause mortality in patients with GPA, independent of other traditional risk factors for mortality and antifungal exposure, supporting GM decay as a potential surrogate endpoint for future antifungal therapeutic trials. C1 [Koo, Sophia; Bryar, Julie M.; Baden, Lindsey R.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Koo, Sophia; Baden, Lindsey R.; Marty, Francisco M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Koo, Sophia; Baden, Lindsey R.; Marty, Francisco M.] Harvard Univ, Sch Med, Boston, MA USA. [Bryar, Julie M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Koo, S (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB A4, Boston, MA 02115 USA. EM skoo@partners.org OI Koo, Sophia/0000-0002-4973-7439 NR 27 TC 43 Z9 43 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2010 VL 48 IS 4 BP 1255 EP 1260 DI 10.1128/JCM.02281-09 PG 6 WC Microbiology SC Microbiology GA 576OC UT WOS:000276153200032 PM 20147646 ER PT J AU Harrington, AT Mahlen, SD Clarridge, JE AF Harrington, Amanda T. Mahlen, Steven D. Clarridge, Jill E., III TI Significantly Larger Numbers of Methicillin-Resistant Staphylococcus aureus Bacteria Are Recovered from Polymicrobial Respiratory and Wound Sites by Use of Chromogenic Primary Media than by Use of Conventional Culture SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID MRSA-SELECT; CHROMAGAR MRSA; NASAL CARRIAGE; SWABS; MRSASELECT; THROAT; ASSAY; AGAR AB Previous studies have validated the properties and documented the utility of chromogenic agar for surveillance of methicillin-resistant Staphylococcus aureus (MRSA). In this study, we used one of the chromagars, MRSASelect (Bio-Rad), as one of the primary isolation media for selected wound and respiratory clinical specimens which, in our institution, were typically polymicrobial. We examined a total of 638 specimens; 142 (22%) MRSA isolates were recovered. Twenty-six of these isolates were recovered only on the MRSASelect plate, representing a 28% (15/54) increase for endotracheal aspirates/sputa and a 15% increase for superficial wounds/ulcers (11/73) compared to the results with conventional culture. One isolate (1 CFU) was recovered by conventional medium alone. MRSASelect has generally been used for surveillance cultures; however, we document that an additional 21% of MRSA isolates would have gone unreported in these selected clinical specimens using only standard culture media. For 40% (6/15) of inpatients, MRSA isolated from the MRSASelect plate was the sole indicator of MRSA. Although these isolates can represent either colonization or infection, they are a potential reservoir of infection and nosocomial transmission. Our data support the focused use of chromogenic selective media for the increased detection of MRSA in polymicrobial wound and respiratory specimens, which could have an impact on both clinical treatment and infection control. C1 [Harrington, Amanda T.; Clarridge, Jill E., III] Puget Sound Hlth Care Syst, Seattle, WA USA. [Mahlen, Steven D.; Clarridge, Jill E., III] Univ Washington, Seattle, WA 98195 USA. RP Clarridge, JE (reprint author), VA Puget Sound Hlth Care Syst, Dept Pathol & Lab Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jill.clarridge@va.gov FU VA Puget Sound Health Care System, Seattle, WA FX This material is the result of work supported in part by resources from the VA Puget Sound Health Care System, Seattle, WA. NR 15 TC 9 Z9 10 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2010 VL 48 IS 4 BP 1350 EP 1353 DI 10.1128/JCM.01770-09 PG 4 WC Microbiology SC Microbiology GA 576OC UT WOS:000276153200046 PM 20181901 ER PT J AU Karakis, I Montouris, GD Otis, JAD Douglass, LM Jonas, R Velez-Ruiz, N Wilford, K Espinosa, PS AF Karakis, Ioannis Montouris, Georgia D. Otis, James A. D. Douglass, Laurie M. Jonas, Rinat Velez-Ruiz, Naymee Wilford, Kesha Espinosa, Patricio S. TI A Quick and Reliable EEG Montage for the Detection of Seizures in the Critical Care Setting SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; Hairline montage; Seizures; Status epilepticus; Critical care; Neurologic intensive care unit ID NONCONVULSIVE STATUS EPILEPTICUS; SCREENING TOOL; HAIRLINE EEG; UNIT AB Obtaining an emergent EEG for the diagnosis of nonconvulsive status epilepticus and conconvulsive seizures in the intensive care unit raises logistic problems in most hospitals. Previous studies have looked into the hairline EEG for a broader population than the critically ill, with controversial conclusions. The authors created a montage sufficiently simple to be performed and interpreted by residents and rapidly achievable to meet the time constraints of a busy on-call schedule. Seven electrodes (Fp1, Fp2, T3, T4, O1, O2, and Cz), easily applied without the need for tape measure by using only anatomic landmarks (pupils, ears, vertex, and inion), were used to configure three different montages: double diamond, circumferential, and Cz referential. EEG records obtained with the full 10-20 system in critically ill patients were reformatted into these montages and reviewed retrospectively independently by neurology attending physicians with expertise in EEG interpretation and senior neurology residents. A comparison was done with the previously studied hairline EEG. The average sensitivity of the study montage for seizure detection was 92.5%, whereas the average specificity was 93.5%. These results suggest that the seven-electrode montage could potentially be a quick and reliable EEG montage for the detection of seizures in the intensive care unit, when technical support is not available. Further prospective studies are required to validate these promising results in a larger population sample. C1 [Karakis, Ioannis; Montouris, Georgia D.; Otis, James A. D.; Wilford, Kesha] Boston Univ, Sch Med, Boston Med Ctr, Dept Neurol, Boston, MA 02118 USA. [Douglass, Laurie M.; Jonas, Rinat] Boston Univ, Sch Med, Boston Med Ctr, Dept Pediat Neurol, Boston, MA 02118 USA. [Velez-Ruiz, Naymee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Espinosa, Patricio S.] Ctr Int Neurociencias, Quito, Ecuador. RP Karakis, I (reprint author), Boston Univ, Med Ctr, Dept Neurol, 715 Albany St,C 329, Boston, MA 02118 USA. EM ioannis.karakis@bmc.org NR 12 TC 20 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD APR PY 2010 VL 27 IS 2 BP 100 EP 105 DI 10.1097/WNP.0b013e3181d649e4 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 580QO UT WOS:000276464500003 PM 20234318 ER PT J AU Neuwelt, EA Brock, P AF Neuwelt, Edward A. Brock, Penelope TI Critical Need for International Consensus on Ototoxicity Assessment Criteria SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID INDUCED HEARING-LOSS; CISPLATIN-INDUCED OTOTOXICITY; CHILDRENS-ONCOLOGY-GROUP; CHILDHOOD HEPATOBLASTOMA; SODIUM THIOSULFATE; N-ACETYLCYSTEINE; AMIFOSTINE; PLATINUM; TUMORS; MEDULLOBLASTOMA C1 [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. [Brock, Penelope] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Brock, Penelope] Inst Child Hlth, London, England. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 26 TC 22 Z9 22 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2010 VL 28 IS 10 BP 1630 EP 1632 DI 10.1200/JCO.2009.26.7872 PG 3 WC Oncology SC Oncology GA 576NS UT WOS:000276152200004 PM 20194840 ER PT J AU Earle, CC Chretien, Y Morris, C Ayanian, JZ Keating, NL Polgreen, LA Wallace, R Ganz, PA Weeks, JC AF Earle, Craig C. Chretien, Yves Morris, Carl Ayanian, John Z. Keating, Nancy L. Polgreen, Linnea A. Wallace, Robert Ganz, Patricia A. Weeks, Jane C. TI Employment Among Survivors of Lung Cancer and Colorectal Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER; WORK; DIAGNOSIS; COHORT; COSTS AB Purpose To identify the frequency of and factors associated with changes in employment among cancer survivors. Methods This prospective cohort study took place in the context of the population-based Cancer Care Outcomes Research and Surveillance Consortium. Patients with nonmetastatic lung or colorectal cancer who survived approximately 15 months after diagnosis without cancer recurrence provided their self-reported employment status, employment experiences, and changes in insurance coverage at 4 and 15 months after diagnosis. Multiple logistic regression was used to relate sociodemographic and disease factors to the probability of labor force departure. Results Among 2,422 eligible patients, employment declined from 39% to 31% over the 15 months after cancer was diagnosed. Labor force departures attributable to cancer occurred in 17% of those employed at baseline. Factors associated with significantly higher rates of labor force departure were lung versus colon cancer, stage III versus I or II disease, lower educational and income levels, and, among colorectal patients, older age. Married women were significantly more likely than unmarried women to leave the workforce. Only 2% of patients lacked health insurance during the study period. Conclusion Most employed patients with nonmetastatic lung or colorectal cancer return to work, but approximately one sixth of patients leave the workforce, particularly those with worse prognoses or lower socioeconomic status. Potential economic effects must be considered in management decisions about cancer. J Clin Oncol 28: 1700-1705. (C) 2010 by American Society of Clinical Oncology C1 Inst Clin Evaluat Sci, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Harvard Univ, Dept Stat, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Iowa, Dept Pharm Practice & Sci, Iowa City, IA USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. RP Earle, CC (reprint author), 2075 Bayview Ave,Room G-106, Toronto, ON M4N 3M5, Canada. EM craig.earle@ices.on.ca FU National Cancer Institute (NCI) [U01 CA093344, U01 CA093332, U01 CA093324, U01 CA093348, U01 CA093329, U01 CA01013, U01 CA093326]; Department of Veteran's Affairs [CRS 02-164] FX Supported by Grant No. U01 CA093344 from the National Cancer Institute (NCI) to the Statistical Coordinating Center; by NCI-supported Primary Data Collection and Research Centers Grants No. U01 CA093332 to Dana-Farber Cancer Institute/Cancer Research Network, U01 CA093324 to Harvard Medical School/Northern California Cancer Center, U01 CA093348 to RAND/University of California, Los Angeles, U01 CA093329 to University of Alabama at Birmingham, U01 CA01013 to University of Iowa, U01 CA093326 to University of North Carolina; and by a Department of Veteran's Affairs grant to the Durham VA Medical Center CRS 02-164. NR 26 TC 31 Z9 32 U1 1 U2 14 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2010 VL 28 IS 10 BP 1700 EP 1705 DI 10.1200/JCO.2009.24.7411 PG 6 WC Oncology SC Oncology GA 576NS UT WOS:000276152200015 PM 20194860 ER PT J AU Walter, RB Kantarjian, HM Huang, XL Pierce, SA Sun, ZX Gundacker, HM Ravandi, F Faderl, SH Tallman, MS Appelbaum, FR Estey, EH AF Walter, Roland B. Kantarjian, Hagop M. Huang, Xuelin Pierce, Sherry A. Sun, Zhuoxin Gundacker, Holly M. Ravandi, Farhad Faderl, Stefan H. Tallman, Martin S. Appelbaum, Frederick R. Estey, Elihu H. TI Effect of Complete Remission and Responses Less Than Complete Remission on Survival in Acute Myeloid Leukemia: A Combined Eastern Cooperative Oncology Group, Southwest Oncology Group, and M. D. Anderson Cancer Center Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GEMTUZUMAB OZOGAMICIN; POTENTIAL CURE; DIAGNOSIS; EFFICACY; CRITERIA; SAFETY; AML AB Purpose It is known that complete remission (CR) prolongs survival in acute myeloid leukemia (AML). In 2003, less stringent response categories were introduced, most notably CR with incomplete platelet recovery (CRp). Although the significance of CRp for survival remains unclear, reports of AML trials frequently combine CR with CRp rather than considering CR as a separate entity. Patients and Methods This practice led us to retrospectively examine the effect of CR on outcome in newly diagnosed AML, by using data from 6,283 patients treated on Eastern Cooperative Oncology Group (ECOG) and Southwest Oncology Group (SWOG) protocols or at M. D. Anderson Cancer Center. This effect was then contrasted with the effect of CRp in the M. D. Anderson Cancer Center cohort. Results At least 94% of patients receiving cytarabine-based therapy and surviving for more than 3 or 5 years achieved a CR with either initial or salvage therapy; limited data suggest the same for patients receiving initial therapies that did not contain cytarabine. Patients with CR were more likely to live beyond 3 or 5 years than patients with CRp. The likelihood of achieving a CR rather than CRp was greater for patients with AML who had better prognosis. After adjustment for covariates, the relapse-free survival of patients achieving CR was longer than that of patients achieving CRp, whereas patients with CRp survived longer than those with resistant disease. Conclusion Our data indicate that CR is of unique clinical significance and should be reported as separate response in trials of newly diagnosed AML. Nonetheless, our findings validate CRp as a clinically meaningful response. J Clin Oncol 28: 1766-1771. (C) 2010 by American Society of Clinical Oncology C1 [Walter, Roland B.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Ctr Stat, Seattle, WA 98109 USA. Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. Univ Washington, Div Med Oncol, Seattle, WA 98195 USA. Univ Texas MD Anderson Canc Ctr, Leukemia Dept, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Walter, RB (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D2-190, Seattle, WA 98109 USA. EM rwalter@fhcrc.org RI Walter, Roland/C-1064-2008 OI Walter, Roland/0000-0002-9268-3341 FU National Cancer Institute [K23CA137161] FX Supported in part by Career Development Award No. K23CA137161 from the National Cancer Institute (R.B.W.). NR 12 TC 76 Z9 79 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2010 VL 28 IS 10 BP 1766 EP 1771 DI 10.1200/JCO.2009.25.1066 PG 6 WC Oncology SC Oncology GA 576NS UT WOS:000276152200024 PM 20159819 ER PT J AU Teles, RP Gursky, LC Faveri, M Rosa, EA Teles, FRF Feres, M Socransky, SS Haffajee, AD AF Teles, Ricardo P. Gursky, Lauren C. Faveri, Marcelo Rosa, Edvaldo A. Teles, Flavia R. F. Feres, Magda Socransky, Sigmund S. Haffajee, Anne D. TI Relationships between subgingival microbiota and GCF biomarkers in generalized aggressive periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE biomarkers; generalized aggressive periodontitis; gingival crevicular fluid; microbiota ID GINGIVAL CREVICULAR FLUID; EARLY-ONSET PERIODONTITIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PORPHYROMONAS-GINGIVALIS; AGGREGATIBACTER-ACTINOMYCETEMCOMITANS; CYTOKINES; PARAMETERS; CHALLENGE; PATHOGENS AB P>Aim To examine relationships between subgingival biofilm composition and levels of gingival crevicular fluid (GCF) cytokines in periodontal health and generalized aggressive periodontitis (GAP). Materials and Methods Periodontal parameters were measured in 25 periodontally healthy and 31 GAP subjects. Subgingival plaque and GCF samples were obtained from 14 sites from each subject. Forty subgingival taxa were quantified using checkerboard DNA-DNA hybridization and the concentrations of eight GCF cytokines were measured using Luminex. Cluster analysis was used to define sites with similar subgingival microbiotas in each clinical group. Significance of differences in clinical, microbiological and immunological parameters among clusters was determined using the Kruskal-Wallis test. Results GAP subjects had statistically significantly higher GCF levels of interleukin-1 beta (IL-1 beta) (p < 0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (p < 0.01) and IL-1 beta/IL-10 ratio (p < 0.001) and higher proportions of Red and Orange complex species than periodontally healthy subjects. There were no statistically significant differences in the mean proportion of cytokines among clusters in the periodontally healthy subjects, while the ratio IL-1 beta/IL-10 (p < 0.05) differed significantly among clusters in the aggressive periodontitis group. Conclusions Different subgingival biofilm profiles are associated with distinct patterns of GCF cytokine expression. Aggressive periodontitis subjects were characterized by a higher IL-1 beta/IL-10 ratio than periodontally healthy subjects, suggesting an imbalance between pro- and anti-inflammatory cytokines in aggressive periodontitis. C1 [Teles, Ricardo P.; Teles, Flavia R. F.; Socransky, Sigmund S.; Haffajee, Anne D.] Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. [Gursky, Lauren C.; Rosa, Edvaldo A.] Pontif Catholic Univ Parana, Sch Dent, Curitiba, Parana, Brazil. [Faveri, Marcelo; Feres, Magda] Univ Guarulhos, Dept Periodontol, Dent Res Div, Guarulhos, SP, Brazil. RP Teles, RP (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM rteles@forsyth.org RI Faveri, Marcelo/C-4738-2012; Rosa, Edvaldo/B-1228-2008; Feres, Magda/H-7964-2012 OI Rosa, Edvaldo/0000-0001-6087-4365; FU National Institute of Dental and Craniofacial Research [DE-016700, T32 DE-07327]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil [4137-07-8] FX The authors would like to express their appreciation to Dr. Alpdogan Kantarci at the Boston University Goldman School of Dental Medicine for his invaluable support with the Luminex technique. This work was supported in part by research grants DE-016700 and T32 DE-07327 from the National Institute of Dental and Craniofacial Research and grant # 4137-07-8 from the Coordenacao de Aperfeico NR 25 TC 50 Z9 51 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD APR PY 2010 VL 37 IS 4 BP 313 EP 323 DI 10.1111/j.1600-051X.2010.01534.x PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 571CM UT WOS:000275728600001 PM 20447254 ER PT J AU Ghaemi, SN Ostacher, MM El-Mallakh, RS Borrelli, D Baldassano, CF Kelley, ME Filkowski, MM Hennen, J Sachs, GS Goodwin, FK Baldessarini, RJ AF Ghaemi, S. Nassir Ostacher, Michael M. El-Mallakh, Rif S. Borrelli, David Baldassano, Claudia F. Kelley, Mary E. Filkowski, Megan M. Hennen, John Sachs, Gary S. Goodwin, Frederick K. Baldessarini, Ross J. TI Antidepressant Discontinuation in Bipolar Depression: A Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Randomized Clinical Trial of Long-Term Effectiveness and Safety SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTENT-TO-TREAT; SYMPTOMATIC STATUS; MOOD STABILIZERS; MAJOR DEPRESSION; BYPASS-SURGERY; INDUCED MANIA; II DISORDER; SCALE; MAINTENANCE; RELIABILITY AB Objective: To assess long-term effectiveness and safety of randomized antidepressant discontinuation after acute recovery from bipolar depression. Method: In the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, conducted between 2000 and 2007, 70 patients with DSM-IV-diagnosed bipolar disorder (72.5% non-rapid cycling, 70% type I) with acute major depression, initially responding to treatment with antidepressants plus mood stabilizers, and euthymic for 2 months, were openly randomly assigned to antidepressant continuation versus discontinuation for 1-3 years. Mood stabilizers were continued in both groups. Results: The primary outcome was mean change on the depressive subscale of the STEP-BD Clinical Monitoring Form. Antidepressant continuation trended toward less severe depressive symptoms (mean difference in DSM-IV depression criteria =-1.84 [95% CI, -0.08 to 3.771) and mildly delayed depressive episode relapse (HR= 2.13 [1.00-4.561), without increased manic symptoms (mean difference in DSM-IV mania criteria = +0.23 [-0.73 to 1.20]). No benefits in prevalence or severity of new depressive or manic episodes, or overall time in remission, occurred. Type II bipolar disorder did not predict enhanced antidepressant response, but rapid-cycling course predicted 3 times more depressive episodes with antidepressant continuation (rapid cycling = 1.29 vs non-rapid cycling = 0.42 episodes/year, P=.04). Conclusions: This first randomized discontinuation study with modern antidepressants showed no statistically significant symptomatic benefit with those agents in the long-term treatment of bipolar disorder, along with neither robust depressive episode prevention benefit nor enhanced remission rates. Trends toward mild benefits, however, were found in subjects who continued antidepressants. This study also found, similar to studies of tricyclic antidepressants, that rapid-cycling patients had worsened C1 [Ghaemi, S. Nassir] Tufts Med Ctr, Dept Psychiat, Mood Disorders Program, Boston, MA 02111 USA. [Ostacher, Michael M.; Borrelli, David; Hennen, John; Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Ostacher, Michael M.; Borrelli, David; Sachs, Gary S.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Ostacher, Michael M.; Borrelli, David; Sachs, Gary S.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [El-Mallakh, Rif S.] Univ Louisville, Sch Med, Louisville, KY 40292 USA. [Baldassano, Claudia F.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Kelley, Mary E.] Emory Univ, Dept Biostat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Filkowski, Megan M.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Hennen, John; Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Belmont, MA USA. [Goodwin, Frederick K.] George Washington Univ, Sch Med, Washington, DC USA. RP Ghaemi, SN (reprint author), Tufts Med Ctr, Dept Psychiat, Mood Disorders Program, 800 Washington St,Box 1007, Boston, MA 02111 USA. EM nghaemi@tuftsmedicalcenter.org RI Ghaemi, Nassir/J-4934-2013; OI Ostacher, Michael/0000-0003-0353-7535 FU Pfizer FX Dr Ghaemi has received honoraria in the past from Pfizer, GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Janssen, and Abbot; has received grants from Pfizer; and has grants pending with both Pfizer and Janssen. He is not a member of speakers bureaus nor a paid consultant to any pharmaceutical company, and he holds no equity positions in pharmaceutical or biomedical companies. NR 45 TC 69 Z9 71 U1 0 U2 13 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2010 VL 71 IS 4 BP 372 EP 380 DI 10.4088/JCP.08m04909gre PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 588HI UT WOS:000277059300001 PM 20409444 ER PT J AU Marder, SR Sorsaburu, S Dunayevich, E Karagianis, JL Dawe, IC Falk, DM Dellva, MA Carlson, JL Cavazzoni, PA Baker, RW AF Marder, Stephen R. Sorsaburu, Sebastian Dunayevich, Eduardo Karagianis, Jamie L. Dawe, Ian C. Falk, Deborah M. Dellva, Mary Anne Carlson, Janice L. Cavazzoni, Patrizia A. Baker, Robert W. TI Case Reports of Postmarketing Adverse Event Experiences With Olanzapine Intramuscular Treatment in Patients With Agitation SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; SCHIZOPHRENIA; PLACEBO; HALOPERIDOL; LORAZEPAM; MORTALITY; DEMENTIA; EFFICACY; PEOPLE AB Objective: Agitation is a medical emergency with increased risk for poor outcome. Successful treatment often requires intramuscular (IM) psychotropics. Safety data from the first 21 months of olanzapine IM, approved in the United States for the treatment of agitation associated with schizophrenia and bipolar disorder, are presented. Method: A Lilly-maintained safety database was searched for all spontaneous adverse events (AEs) reported in temporal association with olanzapine IM treatment. Results: The estimated worldwide patient exposure to olanzapine IM from January 1, 2004, through September 30, 2005, was 539,000; 160 cases containing AEs were reported from patients with schizophrenia (30%), bipolar disorder (21%), unspecified psychosis (10%), dementia (8%), and depression (5%). Many reported concomitant treatment with benzodiazepines (39%) or other antipsychotics (54%). The most frequently reported events involved the following organ systems: central nervous (21%), cardiac (12%), respiratory (6%), vascular (6%), and psychiatric (5%). Eightythree cases were considered serious, including 29 fatalities. In these fatalities, concomitant benzodiazepines or other antipsychotics were reported in 66% and 76% of cases, respectively. The most frequently reported events in the fatal cases involved the following organ systems: cardiovascular (41%), respiratory (21%), general (17%), and central nervous (10%). The majority of fatal cases (76%) included comorbid conditions and potentially clinically significant risk factors for AEs. Conclusions: Clinicians should use care when treating agitated patients, especially when they present with concurrent medical conditions and are treated with multiple medications, which may increase the risk of poor or even fatal outcomes. Clinicians should use caution when using olanzapine IM and parenteral benzodiazepines simultaneously. J Clin Psychiatry 2010;71(4):433-441 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Marder, Stephen R.] Los Angeles Vet Adm, Los Angeles, CA USA. [Dunayevich, Eduardo] Orexigen Therapeut, La Jolla, CA USA. [Sorsaburu, Sebastian; Falk, Deborah M.; Dellva, Mary Anne; Carlson, Janice L.; Cavazzoni, Patrizia A.; Baker, Robert W.] Lilly Corp Ctr, Eli Lilly, Lilly Res Labs, Indianapolis, IN USA. [Karagianis, Jamie L.] Eli Lilly, Toronto, ON, Canada. [Dawe, Ian C.] Univ Toronto, St Michaels Hosp, Dept Psychiat, Toronto, ON M5B 1W8, Canada. RP Marder, SR (reprint author), W Los Angeles VA Healthcare Ctr, Bldg 210,Room 130,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM marder@UCLA.edu NR 19 TC 12 Z9 12 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2010 VL 71 IS 4 BP 433 EP 441 DI 10.4088/JCP.08m04411gry PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 588HI UT WOS:000277059300008 PM 20156413 ER PT J AU Haggerty, G Blake, M Siefert, CJ AF Haggerty, Greg Blake, Margaret Siefert, Caleb J. TI Convergent and Divergent Validity of the Relationship Profile Test: Investigating the Relationship With Attachment, Interpersonal Distress, and Psychological Health SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE dependence; detachment; adult attachment; attachment avoidance; attachment anxiety; psychological well-being ID CONSTRUCT-VALIDITY; DEPENDENT PERSONALITY; OBJECT RELATIONS; OUTCOME MEASURE; CONNECTEDNESS; BEHAVIOR; DETACHMENT; LINKS; VALIDATION; DISORDERS AB The present study looked to illustrate the convergent and divergent validity of the Relationship Profile Test (RPT), which is a 30-item self-report measuring destructive overdependence, dysfunctional detachment, and healthy dependence. The RPT items are written to draw upon Bornstein's (1992, 1993) 4-component model as well as other essential components of the dimension in question (Bornstein et al., 2003). The results reveal that the subscales of the RPT are related in predictable ways to scores on measures of adult attachment, interpersonal distress, and psychological health and well-being. The clinical implications of the results and the assessment of dependency in the clinical setting are discussed. (C) 2010 Wiley Periodicals, Inc. J Clin Psychol 66: 339-354, 2010. C1 [Haggerty, Greg] Nassau Univ Med Ctr, Garden City, NY USA. [Blake, Margaret] Bellevue Hosp Ctr, New York, NY 10016 USA. [Siefert, Caleb J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Haggerty, G (reprint author), 18 Sexton Rd, Syosset, NY 11791 USA. EM Ghag541@aol.com NR 77 TC 9 Z9 10 U1 2 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD APR PY 2010 VL 66 IS 4 BP 339 EP 354 DI 10.1002/jclp.20654 PG 16 WC Psychology, Clinical SC Psychology GA 567ZQ UT WOS:000275490000001 PM 20127793 ER PT J AU Kobak, KA Leuchter, A DeBrota, D Engelhardt, N Williams, JBW Cook, IA Leon, AC Alpert, J AF Kobak, Kenneth A. Leuchter, Andrew DeBrota, David Engelhardt, Nina Williams, Janet B. W. Cook, Ian A. Leon, Andrew C. Alpert, Jonathan TI Site Versus Centralized Raters in a Clinical Depression Trial Impact on Patient Selection and Placebo Response SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE clinical trials; randomized; placebo effect; methods; outcomes assessments; patient; depressive disorder; Hamilton Depression Rating Scale ID RATING-SCALE; QUALITY AB The use of centralized raters who are remotely linked to sites and interview patients via videoconferencing or teleconferencing has been suggested as away to improve interrater reliability and interview quality. This study compared the effect of site-based and centralized ratings on patient selection and placebo response in subjects with major depressive disorder. Subjects in a 2-center placebo and active comparator controlled depression trial were interviewed twice at each of 3 time points: baseline, 1-week postbaseline, and end point-once by the site rater and once remotely via videoconference by a centralized rater. Raters were blind to each others' scores. A site-based score of greater than 17 on the 17-item Hamilton Depression Rating Scale (HDRS-17) was required for study entry. When examining all subjects entering the study, site-based raters' HDRS-17 scores were significantly higher than centralized raters' at baseline and postbaseline but not at end point. At baseline, 35% of subjects given an HDRS-17 total score of greater than 17 by a site rater were given an HDRS total score of lower than 17 by a centralized rater and would have been ineligible to enter the study if the centralized rater's score was used to determine study entry. The mean placebo change for site raters (7.52) was significantly greater than the mean placebo change for centralized raters (3.18, P < 0.001). Twenty-eight percent were placebo responders (>50% reduction in HDRS) based on site ratings versus 14% for central ratings (P < 0.001). When examining data only from those subjects whom site and centralized raters agreed were eligible for the study, there was no significant difference in the HDRS-17 scores. Findings suggest that the use of centralized raters could significantly change the study sample in a major depressive disorder trial and lead to significantly less change in mood ratings among those randomized to placebo. C1 [Kobak, Kenneth A.; Engelhardt, Nina; Williams, Janet B. W.] MedAvante Inc, Madison, WI 53719 USA. [Leuchter, Andrew; Cook, Ian A.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Leuchter, Andrew; Cook, Ian A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [DeBrota, David] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Williams, Janet B. W.] Columbia Univ, Dept Psychiat, New York, NY USA. [Leon, Andrew C.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Alpert, Jonathan] Harvard Univ, Boston, MA 02115 USA. [Alpert, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kobak, KA (reprint author), MedAvante Inc, 7601 Ganser Way, Madison, WI 53719 USA. EM kkobak@medavante.com OI Alpert, Jonathan/0000-0002-4332-908X FU Eli Lilly Co; Pfizer, Inc. FX This study was cofunded by grants from Eli Lilly & Co and Pfizer, Inc. NR 14 TC 30 Z9 31 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2010 VL 30 IS 2 BP 193 EP 197 DI 10.1097/JCP.0b013e3181d20912 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 571AY UT WOS:000275722300015 PM 20520295 ER PT J AU Herce, ME Chapman, JA Castro, A Garcia-Salyano, G Khoshnood, K AF Herce, Michael E. Chapman, Jacob A. Castro, Arachu Garcia-Salyano, Gabriel Khoshnood, Kaveh TI A Role for Community Health Promoters in Tuberculosis Control in the State of Chiapas, Mexico SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE Community health workers; Tuberculosis; Chiapas; Mexico ID PULMONARY TUBERCULOSIS; SOUTH-AFRICA; THERAPY; PERCEPTIONS; VOLUNTEERS; REGION; BURDEN AB We conducted a qualitative study employing structured interviews with 38 community health workers, known as health promoters, from twelve rural municipalities of Chiapas, Mexico in order to characterize their work and identify aspects of their services that would be applicable to community-based tuberculosis (TB) control programs. Health promoters self-identify as being of Mayan Indian ethnicity. Most are bilingual, speaking Spanish and one of four indigenous Mayan languages native to Chiapas. They volunteer 11 h each week to conduct clinical and public health work in their communities. Over half (53%) work with a botiquin, a medicine cabinet stocked with essential medicines. Fifty-three percent identify TB as a major problem affecting the health of their communities, with one-fifth (21%) of promoters reporting experience caring for patients with known or suspected TB and 29% having attended to patients with hemoptysis. One-third of health promoters have access to antibiotics (32%) and one-half have experience with their administration; 55% complement their biomedical treatments with traditional Mayan medicinal plant therapies in caring for their patients. We describe how health promoters employ both traditional and allopathic medicine to treat the symptoms and diseases they encounter most frequently which include fever, diarrhea, and parasitic infections. We contend that given the complex sociopolitical climate in Chiapas and the state's unwavering TB epidemic and paucity of health care infrastructure in rural areas, efforts to implement comprehensive, community-based TB control would benefit from employing the services of health promoters. C1 [Herce, Michael E.; Castro, Arachu] Brigham & Womens Hosp, Div Global Hlth Equ, Dept Med, Boston, MA 02115 USA. [Chapman, Jacob A.] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Castro, Arachu] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Castro, Arachu] Partners Hlth, Boston, MA 02215 USA. [Garcia-Salyano, Gabriel] EAPSEC, San Cristobal de las Casa 29230, Chiapas, Mexico. [Khoshnood, Kaveh] Yale Univ, Sch Publ Hlth, Div Epidemiol Microbial Dis, New Haven, CT 06520 USA. RP Herce, ME (reprint author), Brigham & Womens Hosp, Div Global Hlth Equ, Dept Med, 651 Huntington Ave,FXB Bldg,7th Floor, Boston, MA 02115 USA. EM mherce@partners.org RI Castro, Arachu/L-6664-2014 OI Castro, Arachu/0000-0003-0428-9174 NR 25 TC 4 Z9 6 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD APR PY 2010 VL 35 IS 2 BP 182 EP 189 DI 10.1007/s10900-009-9206-0 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 586DE UT WOS:000276881000009 PM 20033836 ER PT J AU Webb, CA DeRubeis, RJ Barber, JP AF Webb, Christian A. DeRubeis, Robert J. Barber, Jacques P. TI Therapist Adherence/Competence and Treatment Outcome: A Meta-Analytic Review SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE meta-analysis; therapist; adherence; competence ID TERM INDIVIDUAL PSYCHOTHERAPY; COGNITIVE-BEHAVIORAL THERAPY; BRIEF DYNAMIC THERAPY; TRANSFERENCE INTERPRETATIONS; TREATMENT ADHERENCE; RATING-SCALE; COMPETENCE; ALLIANCE; DEPRESSION; PATIENT AB Objective: The authors conducted a meta-analytic review of adherence-outcome and competence-outcome findings, and examined plausible moderators of these relations. Method: A computerized search of the PsycINFO database was conducted. In addition, the reference sections of all obtained studies were examined for any additional relevant articles or review chapters. The literature search identified 36 studies that met the inclusion criteria. Results: R-type effect size estimates were derived from 32 adherence outcome and 17 competence outcome findings. Neither the mean weighted adherence outcome (r = .02) nor competence outcome (r = .07) effect size estimates were found to be significantly different from zero. Significant heterogeneity was observed across both the adherence outcome and competence outcome effect size estimates, suggesting that the individual studies were not all drawn from the same population. Moderator analyses revealed that larger competence outcome effect size estimates were associated with studies that either targeted depression or did not control for the influence of the therapeutic alliance. Conclusions: One explanation for these results is that, among the treatment modalities represented in this review, therapist adherence and competence play little role in determining symptom change. However, given the significant heterogeneity observed across findings, mean effect sizes must be interpreted with caution. Factors that may account for the nonsignificant adherence outcome and competence outcome findings reported within many of the studies reviewed are addressed. Finally, the implication of these results and directions for future process research are discussed. C1 [Webb, Christian A.; DeRubeis, Robert J.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Barber, Jacques P.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Barber, Jacques P.] Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA USA. RP Webb, CA (reprint author), Univ Penn, Dept Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA. EM webb@sas.upenn.edu OI barber, jacques/0000-0002-8762-2595 FU NIMH NIH HHS [R01 MH061410, R01 MH060998, R01MH061410, R01MH60998] NR 71 TC 173 Z9 174 U1 7 U2 41 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD APR PY 2010 VL 78 IS 2 BP 200 EP 211 DI 10.1037/a0018912 PG 12 WC Psychology, Clinical SC Psychology GA 582CK UT WOS:000276572800007 PM 20350031 ER PT J AU Myers, S Reidy, P French, B McHale, J Chisholm, M Griffin, M AF Myers, Sue Reidy, Patricia French, Brian McHale, Jeanne Chisholm, Margery Griffin, Martha TI Safety Concerns of Hospital-Based New-to-Practice Registered Nurses and Their Preceptors SO JOURNAL OF CONTINUING EDUCATION IN NURSING LA English DT Article ID PERCEPTIONS; EXPERIENCE AB Background: On graduation, nursing students enter a critical transition process to become professional registered nurses (RNs). Methods: Six new-to-practice RN groups and seven preceptor groups convened to explore their views of the safety concerns of new-to-practice RNs. Results: The main learning needs of new-to-practice RNs identified by both preceptors and new-to-practice RNs centered on perceptions of uncertainty about technical aspects of nursing care. Lack of critical thinking and inability to think holistically contributed to increased stress. Preceptors who provided frequent feedback in a positive manner were rated as important to the developmental process of becoming a skilled RN. Conclusion: Safety and learning needs identified in this study are amenable to teaching solutions, both in academia and in the hospital work setting. J Contin Educ Nurs 2010;41(4):163-171. C1 [Myers, Sue; Reidy, Patricia; Chisholm, Margery] Massachusetts Gen Hosp, Inst Hlth Profess, Sch Nursing, Boston, MA 02114 USA. [Griffin, Martha] Boston Med Ctr, Boston, MA USA. RP Myers, S (reprint author), Childrens Cove, POB 427, Barnstable, MA 02630 USA. NR 13 TC 8 Z9 8 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0022-0124 J9 J CONTIN EDUC NURS JI J. Contin. Educ. Nursing PD APR PY 2010 VL 41 IS 4 BP 163 EP 171 DI 10.3928/00220124-20100326-02 PG 9 WC Nursing SC Nursing GA 664BU UT WOS:000282934700006 PM 20411888 ER PT J AU Sober, AJ Tsao, H AF Sober, Arthur J. Tsao, Hensin TI Martin C. Mihm, Jr and the history of the Pigmented Lesion Clinic at the Massachusetts General Hospital SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID STAGE-I MELANOMA; DYSPLASTIC MELANOCYTIC NEVI; LENTIGO-MALIGNA MELANOMA; INDEPENDENT RISK FACTOR; PRIMARY-TUMOR THICKNESS; PROGNOSTIC FACTORS; RECURRENT DISEASE; DESMOPLASTIC MELANOMA; MULTIVARIATE-ANALYSIS; CUTANEOUS MELANOMA C1 [Sober, Arthur J.; Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sober, AJ (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM asober@partners.org NR 53 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2010 VL 37 SU 1 BP 8 EP 11 PG 4 WC Dermatology; Pathology SC Dermatology; Pathology GA 571PG UT WOS:000275766000003 PM 20482670 ER PT J AU Duncan, LM AF Duncan, Lyn McDivitt TI Dermatopathology education at Harvard - Inspired by Martin C. Mihm, Jr, MD, FACP SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. EM duncan@helix.mgh.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2010 VL 37 SU 1 BP 12 EP 18 DI 10.1111/j.1600-0560.2010.01502.x PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA 571PG UT WOS:000275766000004 PM 20482671 ER PT J AU Nazarian, RM Prieto, VG Elder, DE Duncan, LM AF Nazarian, Rosalynn M. Prieto, Victor G. Elder, David E. Duncan, Lyn M. TI Melanoma biomarker expression in melanocytic tumor progression: a tissue microarray study SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID MICROPHTHALMIA TRANSCRIPTION FACTOR; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; FACTOR MITF; DIAGNOSIS; MARKER; SURVIVAL; BENIGN; GENE AB Methods: The TMA contains 480 cores of benign nevi, primary cutaneous melanoma and melanoma metastases. Immunohistochemical detection of melanoma biomarkers, including c-Kit, MITF, MART-1, HMB-45 and bcl-2 was performed. Results: Intense nuclear staining for MITF protein was observed in 83% of nevi, 56% of primary melanomas and 23% of metastases. Bcl-2 expression was reduced with progression to metastasis (detected in 86, 89 and 52% of nevi, primaries and metastases, respectively), contrary to MART-1, which showed no differential expression (74, 85 and 84%). HMB-45 was observed in 18% of nevi and most (72 and 75%) primary melanomas and metastases. c-Kit protein increased with progression from nevi to primary tumor (10 and 77% of cases, respectively) and was decreased in metastases (26% of cases). Conclusions: Through a collaboration of the Skin SPOREs sponsored by the Organ Systems Branch of the National Cancer Institute (NCI), we identified a list of melanoma biomarkers of interest, developed a melanocytic tumor progression TMA and completed a coordinated analysis of these biomarkers. This TMA has served as a powerful validation tool for newly identified and known melanoma biomarkers by revealing trends in expression during tumor progression and by confirming the heterogeneity of biomarker expression in cutaneous melanocytic tumors. Nazarian RM, Prieto VG, Elder DE, Duncan LM. Melanoma biomarker expression in melanocytic tumor progression: a tissue microarray study. C1 [Nazarian, Rosalynn M.; Duncan, Lyn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, Boston, MA 02114 USA. [Prieto, Victor G.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Elder, David E.] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, WRN 820,55 Fruit St, Boston, MA 02114 USA. EM duncan@helix.mgh.harvard.edu OI Nazarian, Rosalynn/0000-0003-4003-7193 NR 24 TC 39 Z9 39 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2010 VL 37 SU 1 BP 41 EP 47 DI 10.1111/j.1600-0560.2010.01505.x PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA 571PG UT WOS:000275766000007 PM 20482674 ER PT J AU Hodi, FS Dranoff, G AF Hodi, F. Stephen Dranoff, Glenn TI The biologic importance of tumor-infiltrating lymphocytes SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; REGULATORY T-CELLS; HUMAN REGRESSIVE MELANOMA; ANTITUMOR IMMUNITY; CTLA-4 BLOCKADE; COMBINATION IMMUNOTHERAPY; METASTATIC MELANOMA; OVARIAN-CANCER; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER AB Hodi FS, Dranoff G. The biologic importance of tumor-infiltrating lymphocytes. C1 [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 520C,44 Binney St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu FU NCI NIH HHS [R01 CA143083, P01 CA078378] NR 69 TC 12 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2010 VL 37 SU 1 BP 48 EP 53 DI 10.1111/j.1600-0560.2010.01506.x PG 6 WC Dermatology; Pathology SC Dermatology; Pathology GA 571PG UT WOS:000275766000008 PM 20482675 ER PT J AU Loewe, R Oble, DA Valero, T Zukerberg, L Mihm, MC Nelson, JS AF Loewe, Robert Oble, Darryl A. Valero, Teresa Zukerberg, Lawrence Mihm, Martin C., Jr. Nelson, J. Stuart TI Stem cell marker upregulation in normal cutaneous vessels following pulsed-dye laser exposure and its abrogation by concurrent rapamycin administration: implications for treatment of port-wine stain birthmarks SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID ENDOTHELIAL PROGENITOR CELLS; BLOOD-VESSELS; VASCULAR MALFORMATIONS; TUMOR ANGIOGENESIS; IN-VITRO; NESTIN; FLUENCE; SKIN; INVOLVEMENT; EXPRESSION AB Loewe R, Oble DA, Valero T, Zukerberg L, Mihm MC Jr, Nelson JS. Stem cell marker upregulation in normal cutaneous vessels following pulsed-dye laser exposure and its abrogation by concurrent rapamycin administration: implications for treatment of port-wine stain birthmarks. C1 [Loewe, Robert; Oble, Darryl A.; Zukerberg, Lawrence; Mihm, Martin C., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Loewe, Robert; Valero, Teresa] Med Univ Vienna, Div Gen Dermatol, Dept Dermatol, A-1090 Vienna, Austria. [Nelson, J. Stuart] Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92715 USA. RP Mihm, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Warren Bldg 827,279 Charles St, Boston, MA 02114 USA. EM mmihm@partners.org FU National Institutes of Health [AR47551, EB002495] FX We would like to thank Sandra Kirley and Silvia Steele for their excellent technical assistance. This project was supported by research grants awarded from the National Institutes of Health (AR47551 and EB002495) to JSN. This work was presented in part at the 29th Annual Conference of the American Society for Laser Medicine and Surgery in National Harbor, MD, on April 3, 2009. NR 29 TC 20 Z9 20 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2010 VL 37 SU 1 BP 76 EP 82 DI 10.1111/j.1600-0560.2010.01520.x PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA 571PG UT WOS:000275766000012 PM 20482679 ER PT J AU Mihm, MC Nelson, JS AF Mihm, Martin C., Jr. Nelson, J. Stuart TI Hypothesis: The metastatic niche theory can elucidate infantile hemangioma development SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID JUVENILE HEMANGIOMAS; STEM-CELLS; EXPRESSION AB Mihm MC, Nelson JS. Hypothesis: the metastatic niche theory can elucidate infantile hemangioma development. C1 [Mihm, Martin C., Jr.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mihm, Martin C., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nelson, J. Stuart] Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92612 USA. RP Mihm, MC (reprint author), Harvard Univ, Sch Med, 55 Fruit St,Warren 825, Boston, MA 02114 USA. EM Mihm.martin@mgh.harvard.edu FU NCRR NIH HHS [P41 RR001192-31, P41 RR001192, P41 RR001192-32, P41 RR001192-30] NR 23 TC 19 Z9 20 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2010 VL 37 SU 1 BP 83 EP 87 DI 10.1111/j.1600-0560.2010.01521.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA 571PG UT WOS:000275766000013 PM 20482680 ER PT J AU Tannous, Z Rubeiz, N Kibbi, AG AF Tannous, Zeina Rubeiz, Nelly Kibbi, Abdul-Ghani TI Vascular anomalies: portwine stains and hemangiomas SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID PULSED-DYE-LASER; 5-PERCENT IMIQUIMOD CREAM; WINE STAINS; INFANTILE HEMANGIOMAS; BLOOD-VESSELS; JUVENILE HEMANGIOMAS; INFANCY; BIRTHMARKS; GROWTH; LIGHT C1 [Tannous, Zeina] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rubeiz, Nelly; Kibbi, Abdul-Ghani] Amer Univ Beirut, Med Ctr, Dept Dermatol, Beirut, Lebanon. RP Tannous, Z (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM ztannous1@hotmail.com NR 55 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2010 VL 37 SU 1 BP 88 EP 95 PG 8 WC Dermatology; Pathology SC Dermatology; Pathology GA 571PG UT WOS:000275766000014 PM 20482681 ER PT J AU Piris, A Lobo, AZC Moschella, SL AF Piris, Adriano Lobo, Alice Z. C. Moschella, Samuel L. TI Global dermatopathology: Hansen's disease - current concepts and challenges SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID ERYTHEMA-NODOSUM LEPROSUM; HISTOID LEPROSY; LEPROMATOUS LEPROSY; MYCOBACTERIUM-LEPRAE; MULTIDRUG THERAPY; LUCIOS PHENOMENON; RELAPSE C1 [Piris, Adriano] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Piris, Adriano; Moschella, Samuel L.] Harvard Univ, Sch Med, Boston, MA USA. [Lobo, Alice Z. C.] Univ Sao Paulo, Hosp Clin, Sao Paulo, Brazil. [Moschella, Samuel L.] Lahey Clin Med Ctr, Dept Dermatol, Burlington, MA 01803 USA. RP Piris, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM apiris@partners.org NR 46 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2010 VL 37 SU 1 BP 125 EP 136 PG 12 WC Dermatology; Pathology SC Dermatology; Pathology GA 571PG UT WOS:000275766000017 PM 20482684 ER PT J AU Kanasi, E Johansson, I Lu, SC Kressin, NR Nunn, ME Kent, R Tanner, ACR AF Kanasi, E. Johansson, I. Lu, S. C. Kressin, N. R. Nunn, M. E. Kent, R., Jr. Tanner, A. C. R. TI Microbial Risk Markers for Childhood Caries in Pediatricians' Offices SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE early childhood caries; S. mutans; Lactobacillus ID DENTAL-CARIES; PRESCHOOL-CHILDREN; MOLECULAR ANALYSIS; YOUNG-CHILDREN; DIVERSITY; COLONIZATION; ACCUMULATION; MICROFLORA; DENTITION; BACTERIA AB Dental caries in pre-school children has significant public health and health disparity implications. To determine microbial risk markers for this infection, this study aimed to compare the microbiota of children with early childhood caries with that of caries-free children. Plaque samples from incisors, molars, and the tongue from 195 children attending pediatricians' offices were assayed by 74 DNA probes and by PCR to Streptococcus mutans. Caries-associated factors included visible plaque, child age, race, and snacking habits. Species were detected more frequently from tooth than tongue samples. Lactobacillus gasseri (p < 0.01), Lactobacillus fermentum, Lactobacillus vaginalis, and S. mutans with Streptococcus sobrinus (all p < 0.05) were positively associated with caries. By multifactorial analysis, the probiotic Lactobacillus acidophilus was negatively associated with caries. Prevotella nigrescens was the only species (p < 0.05) significantly associated with caries by the 'false discovery' rate. Analysis of the data suggests that selected Lactobacillus species, in addition to mutans streptococci, are risk markers for early childhood caries. C1 [Kanasi, E.; Lu, S. C.; Tanner, A. C. R.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. [Kent, R., Jr.] Forsyth Inst, Dept Biostat, Boston, MA 02115 USA. [Kanasi, E.; Kent, R., Jr.] Harvard Univ, Harvard Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. [Tanner, A. C. R.] Harvard Univ, Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Johansson, I.] Umea Univ, Dept Odontol, Fac Med, Sect Cariol, S-90187 Umea, Sweden. [Kanasi, E.] Umea Univ, Dept Odontol, Fac Med, Sect Oral Microbiol, S-90187 Umea, Sweden. [Kressin, N. R.; Nunn, M. E.] Boston Univ, Sch Med, Goldman Sch Dent Med, NE Ctr Res Evaluate & Eliminate Dent Dispar CREED, Boston, MA 02118 USA. [Kressin, N. R.] Boston Univ, Sch Med, Healthcare Dispar Res Program, Gen Internal Med Sect,Dept Med, Boston, MA 02118 USA. [Kressin, N. R.] Boston Univ, Sch Med, Dept Vet Affairs, Boston VA Med Ctr, Boston, MA 02118 USA. RP Tanner, ACR (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM annetanner@forsyth.org OI Kressin, Nancy/0000-0003-2767-4286 FU USPHS [U54 DE-014264, DE-015847, DE-007151-18, DE-007327-07]; National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA [K24 DE000419]; Umea University, Sweden FX We thank Harpreet Singh and Cindy Cadoret for subject recruitment, clinical measurements, and sampling. This investigation was supported by USPHS grants U54 DE-014264, DE-015847, DE-007151-18, DE-007327-07, and K24 DE000419 from the National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA, and by a Medical Faculty PhD grant, Umea University, Sweden. NR 34 TC 41 Z9 45 U1 4 U2 11 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 APR PY 2010 VL 89 IS 4 BP 378 EP 383 DI 10.1177/0022034509360010 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 568ZZ UT WOS:000275566800010 PM 20164496 ER PT J AU Janket, S Meurman, JH Baird, AE Qvarnstrom, M Nuutinen, P Ackerson, LK Hong, J Muthukrishnan, P Van Dyke, TE AF Janket, S. Meurman, J. H. Baird, A. E. Qvarnstrom, M. Nuutinen, P. Ackerson, L. K. Hong, J. Muthukrishnan, P. Van Dyke, T. E. TI Salivary Immunoglobulins and Prevalent Coronary Artery Disease SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE coronary artery disease; inflammation; infection; salivary immunoglobulins; mucosal antigenicity ID PNEUMONIAE IGA TITERS; C-REACTIVE PROTEIN; CHLAMYDIA-PNEUMONIAE; HEART-DISEASE; CARDIOVASCULAR-DISEASE; PERIODONTAL-DISEASE; RISK; METAANALYSIS; ANTIBODY; STROKE AB Previous studies examined the serum immunoglobulin levels in relation to coronary artery disease (CAD). We hypothesized that the salivary immunoglobulins might better estimate oral infections in this relationship. Multivariate logistic regression analyses utilizing the data from 256 angiographically confirmed CAD patients and 250 non-CAD individuals that controlled for age, sex, smoking, diabetes, total/HDL cholesterol ratio, hypertension, and education revealed the trends that salivary IgA was positively and salivary IgG was inversely associated with CAD. The odds ratios (OR) of each increasing quartile of salivary IgA were 1.00 (first and second quartiles combined), 1.97, and 1.37 (p-value for trend = 0.06), while those for salivary IgG were 1.00, 0.77, 0.60, and 0.51 (p-value for trend = 0.02). Additionally, salivary IgA correlated positively with C-reactive protein and Asymptotic Dental Score (dental infection score), while IgG was inversely associated with these inflammation markers. Salivary IgA warrants further studies to confirm its role in the risk assessment of CAD. C1 [Janket, S.; Muthukrishnan, P.] Boston Univ, Sch Dent Med, Boston, MA 02118 USA. [Meurman, J. H.] Univ Helsinki, Inst Dent, FIN-00014 Helsinki, Finland. [Meurman, J. H.] Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. [Baird, A. E.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Qvarnstrom, M.] Univ Kuopio, FIN-70211 Kuopio, Finland. [Nuutinen, P.] Kuopio Univ Hosp, Kuopio, Finland. [Ackerson, L. K.] Univ Massachusetts Lowell, Lowell, MA USA. [Hong, J.] Boston Univ, Coll Arts & Sci, Boston, MA 02215 USA. [Muthukrishnan, P.] Massachusetts Gen Hosp, Randomized Trial Unit, Boston, MA 02114 USA. [Janket, S.; Van Dyke, T. E.] Boston Univ, Sch Dent Med, Boston, MA 02215 USA. RP Janket, S (reprint author), Boston Univ, Sch Dent Med, 100 E Newton St,Rm G-619, Boston, MA 02118 USA. EM skjanket@bu.edu OI Janket, Sok-Ja/0000-0003-0078-3992; Meurman, Jukka/0000-0001-6702-6836 FU American Heart Association [0635351N]; Helsinki University Central Hospital, Helsinki, Finland [TYH 3245]; NIH [DE13191]; USPHS [DE15566] FX This study was supported by a grant from the American Heart Association (#0635351N) to S. Janket. J.H. Meurman is supported by grant TYH 3245 from the Helsinki University Central Hospital, Helsinki, Finland. T. E. Van Dyke is supported by NIH grant DE13191 and USPHS grant DE15566. The abstract of this study was presented at the 76th Congress of the European Atherosclerosis Society in Helsinki, Finland, in June, 2007. NR 31 TC 7 Z9 8 U1 0 U2 2 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 APR PY 2010 VL 89 IS 4 BP 389 EP 394 DI 10.1177/0022034509359884 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 568ZZ UT WOS:000275566800012 PM 20177131 ER PT J AU Jellinek, MS Hirst, J Stein, MT AF Jellinek, Michael S. Hirst, Jeremy Stein, Martin T. TI Giving Bad News: A 13-Year Old With Acute Psychotic Symptoms and Catatonia SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article AB CASE: Scott, a 13-year 7-month old white male with no prior psychiatric history, presented to the emergency department after three days of decreased attention span and increased distractibility. An initial examination revealed that he was internally preoccupied (focused on responding to auditory hallucinations), displayed thought blocking (sudden interruption in the flow of his thoughts that prevented him from completing an idea), and he had periodic vague suicidal ideation due to intense guilt. He noted hearing two to three voices accusing him of being rude during an incident with a peer at school. He could not accept reassurance from his mother and grandparents that this incident had not actually occurred. Scott found evidence of his wrongdoing by misinterpreting words on signs and medical equipment that he felt indicated that others also knew of his malicious actions. A recent stressor included the conclusion of his active football season a day prior to the onset of his symptoms. Scott and his family denied a history of prodromal symptoms, mental or medical illnesses, including head injury. After a physical/neurological examination, a negative urine drug screen, and a normal complete blood count and metabolic panel, Scott was transferred to a psychiatric hospital. Scott returned to the emergency department two days later with worsening psychotic symptoms despite a trial of olanzapine. He had deteriorated dramatically from his initial presentation. He was now rigid, unable to speak, move his body, follow directions, eat, drink, or provide any additional history. After being admitted to the pediatrics floor an extensive medical workup was completed that included neurology and infectious disease consults, brain magnetic resonance imaging and angiography studies, a 24-hour electroencephalogram, lumbar puncture, urinalysis, complete blood count, comprehensive metabolic panel, ceruloplasm, anti-nuclear antibody, anti-DNAase, erythrocyte sedimentation rate, heavy metal screen, ammonia, rapid plasma reagin (RPR), and human immunodeficiency virus. All laboratory studies were normal. C1 [Jellinek, Michael S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Jellinek, Michael S.] Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. [Hirst, Jeremy] Univ Calif San Diego, Dept Child & Adolescent Psychiat, San Diego, CA 92103 USA. [Stein, Martin T.] Univ Calif San Diego, Rady Childrens Hosp San Diego, San Diego, CA 92103 USA. RP Jellinek, MS (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD APR PY 2010 VL 31 IS 3 SU S BP S103 EP S106 DI 10.1097/DBP.0b013e3181d8311b PG 4 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 589WS UT WOS:000277185500028 PM 20414058 ER PT J AU Shapiro, HL Prince, JB Ireland, R Stein, MT AF Shapiro, Henry L. Prince, Jefferson B. Ireland, Rachel Stein, Martin T. TI A Dominating Imaginary Friend, Cruelty to Animals, Social Withdrawal, and Growth Deficiency in a 7-Year-Old Girl With Parents With Schizophrenia SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE social withdrawal; imaginary companion; schizophrenia ID CHILDHOOD-ONSET SCHIZOPHRENIA; AGGRESSIVE YOUTH TRAAY; HELSINKI HIGH-RISK; PSYCHOTIC DISORDER; TREATMENT RECOMMENDATIONS; CHILDREN; COMPANIONS; HALLUCINATIONS; ANTIPSYCHOTICS; SYMPTOMS AB CASE: Tessa is a 7-year-old girl with odd behaviors, worsening over the preceding year. She spends a significant amount of time alone in her room, talking to "Richard." Her father observed that Tessa is "in her own world." In school, she often glares at the teacher and refuses to work. She is alone at recess without any real friends. Her father reports that she eats little and only after he tastes the food. She is increasingly cruel to both real and toy animals. She tied a string around her cat's neck and swung it around, saying she wanted to punish it. She was heard to say to her stuffed cat, "Die, b ....; die." Richard told her to do this and other "bad" things. Tessa has not had chronic health problems or developmental concerns. During the first 18 months of life, her height was between the 5th and 10th percentiles; it declined to below the 3rd percentile over the past 2 years. Weight has been consistently between the 3rd and 5th percentiles. Tessa's parents both have been diagnosed with schizophrenia. There are at least 7 first-and second-degree relatives with the same diagnosis. Both parents cared for Tessa for 4 years with a lot of support. Then, her father left the home, but he was in contact with her while managing his own illness. When the mother's illness and compliance worsened, Tessa was removed for neglect at 5 1/2 years old. Two foster homes preceded Dad's award of sole custody 13 months ago. Mother's weekly visitations are quite upsetting to Tessa. Tessa is a verbal, solemn, small, well-dressed girl with no physical abnormalities. She talks with advanced vocabulary and syntax, with normal prosody and good conversational skills. She says Richard is a bad boy who gets her into trouble at school. She equivocates when asked if he is real or imagined or if others can see him. She says that she misses her mother. C1 [Shapiro, Henry L.] All Childrens Hosp, St Petersburg, FL USA. [Shapiro, Henry L.] Univ S Florida, Dept Pediat, Coll Med, Tampa, FL 33620 USA. [Prince, Jefferson B.] N Shore Med Ctr, Dept Child Psychiat, Salem, MA USA. [Prince, Jefferson B.] Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, Boston, MA 02114 USA. [Prince, Jefferson B.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Ireland, Rachel; Stein, Martin T.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Shapiro, HL (reprint author), All Childrens Hosp, St Petersburg, FL USA. NR 38 TC 1 Z9 1 U1 5 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD APR PY 2010 VL 31 IS 3 SU S BP S24 EP S29 DI 10.1097/DBP.0b013e3181d831a5 PG 6 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 589WS UT WOS:000277185500009 PM 20414069 ER PT J AU Ibrahimi, OA Eisen, DB Avram, MM Robins, P AF Ibrahimi, Omar A. Eisen, Daniel B. Avram, Mathew M. Robins, Perry TI Ten Pearls for Identifying the Right Dermatologic Surgery Fellowship for You SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Editorial Material C1 [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Combined Program Dermatol,Dept Dermatol, Boston, MA 02114 USA. [Eisen, Daniel B.] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA. [Robins, Perry] NYU, Sch Med, New York, NY USA. RP Ibrahimi, OA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Combined Program Dermatol,Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. EM omar.ibrahimi@gmail.com NR 5 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD APR PY 2010 VL 9 IS 4 BP 421 EP 424 PG 4 WC Dermatology SC Dermatology GA 595MX UT WOS:000277615900030 PM 20514805 ER PT J AU Dushay, J Abrahamson, MJ AF Dushay, Jody Abrahamson, Martin J. TI Insulin therapy for type 2 diabetes: Making it work SO JOURNAL OF FAMILY PRACTICE LA English DT Article ID BETA-CELL FUNCTION; TO-TARGET TRIAL; GLYCEMIC CONTROL; NPH INSULIN; ORAL-THERAPY; MELLITUS; GLARGINE; HYPERGLYCEMIA; ASSOCIATION; MANAGEMENT C1 [Dushay, Jody] Beth Israel Deaconess Med Ctr, Div Endocrinol, Dept Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Abrahamson, Martin J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Abrahamson, Martin J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Sch Med, Boston, MA 02215 USA. RP Dushay, J (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol, Dept Med, Joslin Diabet Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM jdushay@bidmc.harvard.edu FU Pfizer Inc. FX Dr. Dushay reported no potential conflict of interest relevant to this article. Dr. Abrahamson is on the speakers' bureau for Eli Lilly and Company, Merck & Co., Inc., and Novo Nordisk Inc. Dr. Abrahamson also receives research support from Pfizer Inc. NR 39 TC 2 Z9 2 U1 0 U2 0 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD APR PY 2010 VL 59 IS 4 BP E1 EP E8 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 796XE UT WOS:000293086000001 PM 20398575 ER PT J AU Peters, MG Weinbaum, C Tan, L Baine, WB Dienstag, JL Liang, TJ So, S AF Peters, Marion G. Weinbaum, Cindy Tan, Litjen (L. J.) Baine, William B. Dienstag, Jules L. Liang, T. Jake So, Samuel TI Recommendations for prevention, screening, and diagnosis of HBV and HCV infections SO JOURNAL OF FAMILY PRACTICE LA English DT Article ID C VIRUS-INFECTION; HEPATITIS-C; UNITED-STATES; MANAGEMENT; UPDATE C1 [Peters, Marion G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Weinbaum, Cindy] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA. [Tan, Litjen (L. J.)] Amer Med Assoc, Chicago, IL 60610 USA. [Baine, William B.] Agcy Healthcare Res & Qual AHRQ, Rockville, MD USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Boston, MA USA. [Liang, T. Jake] Amer Assoc Study Liver Dis AASLD, Alexandria, VA USA. [So, Samuel] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Peters, MG (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. FU Genentech; NIDDK; Vertex FX Dr Peters reports the following: Consultant: Clinical Care Options, Genentech, Pharmasset. Salary: Dr Peters' spouse receives a salary from Genentech; Dr Dienstag reports the following: Consultant: Abbott Molecular, Boehringer Ingelheim, Bristol-Myers Squibb, Genzyme, Human Genome Sciences, Medtronic, Schering-Plough Research Institute. Grant/Research Support: NIDDK, Vertex. Ownership Interest: Options: Achillion, Metabasis, Nucleonics NR 23 TC 1 Z9 1 U1 0 U2 1 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD APR PY 2010 VL 59 IS 4 SU S BP S29 EP S35 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 796XH UT WOS:000293086300005 PM 20398588 ER PT J AU Fischer, MA Stedman, MR Lii, J Vogeli, C Shrank, WH Brookhart, MA Weissman, JS AF Fischer, Michael A. Stedman, Margaret R. Lii, Joyce Vogeli, Christine Shrank, William H. Brookhart, M. Alan Weissman, Joel S. TI Primary Medication Non-Adherence: Analysis of 195,930 Electronic Prescriptions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE adherence; non-adherence; electronic prescribing; health information technology ID ACUTE MYOCARDIAL-INFARCTION; PHARMACOLOGICAL CARE; UNITED-STATES; DRUG-THERAPY; ADHERENCE; QUALITY; PERSISTENCE; HOSPITALIZATION; HYPERTENSION; PREDICTORS AB Non-adherence to essential medications represents an important public health problem. Little is known about the frequency with which patients fail to fill prescriptions when new medications are started ("primary non-adherence") or predictors of failure to fill. Evaluate primary non-adherence in community-based practices and identify predictors of non-adherence. 75,589 patients treated by 1,217 prescribers in the first year of a community-based e-prescribing initiative. We compiled all e-prescriptions written over a 12-month period and used filled claims to identify filled prescriptions. We calculated primary adherence and non-adherence rates for all e-prescriptions and for new medication starts and compared the rates across patient and medication characteristics. Using multivariable regressions analyses, we examined which characteristics were associated with non-adherence. Primary medication non-adherence. Of 195,930 e-prescriptions, 151,837 (78%) were filled. Of 82,245 e-prescriptions for new medications, 58,984 (72%) were filled. Primary adherence rates were higher for prescriptions written by primary care specialists, especially pediatricians (84%). Patients aged 18 and younger filled prescriptions at the highest rate (87%). In multivariate analyses, medication class was the strongest predictor of adherence, and non-adherence was common for newly prescribed medications treating chronic conditions such as hypertension (28.4%), hyperlipidemia (28.2%), and diabetes (31.4%). Many e-prescriptions were not filled. Previous studies of medication non-adherence failed to capture these prescriptions. Efforts to increase primary adherence could dramatically improve the effectiveness of medication therapy. Interventions that target specific medication classes may be most effective. C1 [Fischer, Michael A.; Stedman, Margaret R.; Lii, Joyce; Shrank, William H.; Brookhart, M. Alan] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02120 USA. [Vogeli, Christine; Weissman, Joel S.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Fischer, MA (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM mfischer@partners.org OI Stedman, Margaret/0000-0001-9271-8332 FU AHRQ [R01 HS15175]; NIH [AG12084, HL090505] FX We acknowledge the assistance of BCBSMA, Tufts HP, and ZixCorp in providing data. The investigators retained control over all aspects of the analyses and presentation of results. The research was supported by AHRQ grant R01 HS15175.; Dr. Brookhart is supported by a career development grant from NIH (AG12084).; Dr. Shrank is supported by a career development grant from NIH (HL090505). NR 36 TC 163 Z9 167 U1 1 U2 16 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 APR PY 2010 VL 25 IS 4 BP 284 EP 290 DI 10.1007/s11606-010-1253-9 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 571TS UT WOS:000275779300003 PM 20131023 ER PT J AU Lin, JC Karno, MP Tang, LQ Barry, KL Blow, FC Davis, JW Ramirez, KD Welgreen, S Hoffing, M Moore, AA AF Lin, James C. Karno, Mitchell P. Tang, Lingqi Barry, Kristen L. Blow, Frederic C. Davis, James W. Ramirez, Karina D. Welgreen, Sandra Hoffing, Marc Moore, Alison A. TI Do Health Educator Telephone Calls Reduce At-risk Drinking Among Older Adults in Primary Care? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE alcohol; telephone intervention; health educator; at-risk drinking ID RANDOMIZED-CONTROLLED-TRIAL; BRIEF PHYSICIAN ADVICE; ALCOHOL-USE; GENERAL-PRACTITIONERS; BRIEF INTERVENTION; PROBLEM DRINKERS; CONSUMPTION; MANAGEMENT; PEOPLE; PREVALENCE AB Alcohol screening and brief intervention for unhealthy alcohol use has not been consistently delivered in primary care as part of preventive healthcare. To explore whether telephone-based intervention delivered by a health educator is efficacious in reducing at-risk drinking among older adults in primary care settings. Secondary analyses of data from a randomized controlled trial. Subjects randomized to the intervention arm of the trial (n = 310). Personalized risk reports, advice from physicians, booklet about alcohol and aging, and up to three telephone calls from a health educator. All interventions were completed before the three-month follow-up. Risk outcomes (at-risk or not at-risk) at 3 and 12 months after enrollment. In univariate analyses, compared to those who remained at risk, those who achieved not at-risk outcome at 3 months were more likely to be women, Hispanic or non-white, have lower levels of education, consume less alcohol, drink less frequently, and have lower baseline number of risks. In mixed-effects logistic regression models, completing all three health educator calls increased the odds of achieving not at-risk outcome compared to not completing any calls at 3 months (OR 5.31; 95% CI 1.92-14.7; p = 0.001), but not at 12 months (OR 2.01; 95% CI 0.71-5.67; p = 0.18). Telephone-based intervention delivered by a health educator was moderately efficacious in reducing at-risk drinking at 3 months after enrollment among older adults receiving a multi-faceted intervention in primary care settings; however, the effect was not sustained at 12 months. C1 [Lin, James C.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Lin, James C.; Davis, James W.; Ramirez, Karina D.; Moore, Alison A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Lin, James C.] Cheng Ching Hosp, Dept Med, Taichung, Taiwan. [Karno, Mitchell P.; Moore, Alison A.] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA USA. [Tang, Lingqi] Univ Calif Los Angeles, Hlth Serv Res Ctr, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Barry, Kristen L.; Blow, Frederic C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Welgreen, Sandra] Kaiser Permanente, Panorama City, CA USA. [Hoffing, Marc] Desert Oasis Healthcare, Palm Springs, CA USA. [Moore, Alison A.] Div Geriatr Med, Los Angeles, CA USA. RP Lin, JC (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Ave,Bldg 220,Room 302, Los Angeles, CA 90073 USA. EM jlin1207@ucla.edu FU Special Fellowship in Advanced Geriatrics; VA Greater Los Angeles Healthcare System; National Institutes of Health, National Institute on Alcoholism and Alcohol Abuse [AA013937, AA15957] FX Funding sources: Special Fellowship in Advanced Geriatrics, VA Greater Los Angeles Healthcare System, and the National Institutes of Health, National Institute on Alcoholism and Alcohol Abuse (AA013937 and AA15957) NR 43 TC 17 Z9 17 U1 4 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2010 VL 25 IS 4 BP 334 EP 339 DI 10.1007/s11606-009-1223-2 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 571TS UT WOS:000275779300011 PM 20101471 ER PT J AU Brown, CJ Bradberry, C Howze, SG Hickman, L Ray, H Peel, C AF Brown, Cynthia J. Bradberry, Christy Howze, Shalaney Green Hickman, Lindsay Ray, Heather Peel, Claire TI Defining Community Ambulation From the Perspective of the Older Adult SO JOURNAL OF GERIATRIC PHYSICAL THERAPY LA English DT Article DE aging; mobility; walking AB Background: Little is known regarding destinations and distances necessary for independent community ambulation after enactment of the Americans with Disability Act. Objective: To qualitatively describe community locations visited by older adults and to determine ambulation distance required to visit these locations. Design: Descriptive study. Methods: Nineteen subjects, 65 years or older and who were independent with transportation, ambulation, and basic activities of daily living, were recruited from 4 senior centers in urban areas of central Alabama. The study was divided into 2 phases. In part 1, using qualitative methodology, older adults were interviewed to determine locations they visited in the community. In part 2, we visited the types of locations identified in part 1 and measured distances required to conduct business at each location. Obstacles, if any, to reaching these locations were identified. Results: Subjects had a mean age of 76.6 (5.8) years; 80% were women, and 50% lived alone in the community. Locations visited by subjects were identified and measured. Researchers categorized locations as essential, essential to some people, and nonessential. Essential locations included bank, doctor's office, and either a grocery store, pharmacy, and department store or a "superstore." A minimum of approximately 200 m was required for community ambulation to most locations, although this distance varied significantly among locations. Limitations: Geographic location and urban setting may not reflect distances necessary for rural residents. Conclusions: Physical therapists can use the 200-m distance as a starting point for goal-setting for older adults desiring a return to community independence. C1 [Brown, Cynthia J.] Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. [Brown, Cynthia J.] Univ Alabama, Dept Med, Birmingham, AL USA. [Bradberry, Christy; Howze, Shalaney Green; Hickman, Lindsay; Ray, Heather; Peel, Claire] Univ Alabama, Sch Hlth Profess, Birmingham, W Midlands, England. RP Brown, CJ (reprint author), Birmingham VAMC, GRECC 11-G Room 8226,1530 3rd Ave S, Birmingham, AL 35294 USA. EM cbrownmd@uab.edu FU VA Research Career Development Award [E6326W] FX The authors thank the subjects who participated in this study. C. Bradberry, S. Green, L. Hickman, and H. Ray completed this project in partial fulfillment of the requirements of the doctoral degree (physical therapy), University of Alabama at Birmingham. Dr Brown is a recipient of a VA Research Career Development Award (E6326W) and the John A. Hartford-sponsored Southeast Center of Excellence in Geriatric Medicine Special Fellows award. NR 18 TC 8 Z9 8 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1539-8412 J9 J GERIATR PHYS THER JI J. Geriatr. Phys. Ther. PD APR-JUN PY 2010 VL 33 IS 2 BP 56 EP 63 PG 8 WC Geriatrics & Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA V21PK UT WOS:000208219300003 PM 20718384 ER PT J AU Aye, T Toschi, E Sharma, A Sgroi, D Bonner-Weir, S AF Aye, Tandy Toschi, Elena Sharma, Arun Sgroi, Dennis Bonner-Weir, Susan TI Identification of Markers for Newly Formed beta-Cells in the Perinatal Period: A Time of Recognized beta-Cell Immaturity SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE islet cells; beta-cells; immunohistochemistry ID INDUCED INSULIN RELEASE; ENDOCRINE PANCREAS; HUMAN FETAL; DIFFERENTIATION; PROLIFERATION; GLUCOSE; RAT; REGENERATION; EXPRESSION; MATURATION AB Markers of beta-cell maturity would be useful in staging the differentiation of stem/progenitor cells to beta-cells whether in vivo or in vitro. We previously identified markers for newly formed beta-cells in regenerating rat pancreases after 90% partial pancreatectomy. To test the generality of these markers of newly formed beta-cells, we examined their expression during the perinatal period, a time of recognized beta-cell immaturity. We show by semiquantitative RT-PCR and immunostaining over the time course from embryonic day 18/20 to birth, 1 day, 2 days, 3 days, 7 days, and adult that MMP-2, CK-19, and SPD are truly markers of new and immature beta-cells and that their expression transiently peaks in the perinatal period and is not entirely synchronous. The shared expression of these markers among fetal, newborn, and newly regenerated beta-cells, but not adult, strongly supports their use as potential markers for new beta-cells in the assessment of both the maturity of stem cell derived insulin-producing cells and the presence of newly formed islets (neogenesis) in the adult pancreas. (J Histochem Cytochem 58:369-376, 2010) C1 [Aye, Tandy; Toschi, Elena; Sharma, Arun; Bonner-Weir, Susan] Joslin Diabets Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Sgroi, Dennis] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Bonner-Weir, S (reprint author), Joslin Diabets Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu FU National Institutes of Health [DK-44523, DK-66056, DK-61251]; Joslin Diabetes Endocrine Research Center [DK-36836]; Juvenile Diabetes Research Foundation [JDRF 1-2004-120, 1-2000-389]; Endocrine Fellow Foundation award; Lawson-Wilkins Fellowship FX This research was supported by National Institutes of Health Grants DK-44523 and DK-66056 (to SBW), DK-61251, beta-cell Biology Consortium (to DS), and the cores of the Joslin Diabetes Endocrine Research Center (DK-36836), by the Juvenile Diabetes Research Foundation (JDRF 1-2004-120 to SBW and 1-2000-389 to AS), and an important group of private donors. T.A. was recipient of an Endocrine Fellow Foundation award and a Lawson-Wilkins Fellowship. The authors thank Dr. Gordon Weir for helpful discussions. NR 23 TC 27 Z9 27 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD APR PY 2010 VL 58 IS 4 BP 369 EP 376 DI 10.1369/jhc.2009.954909 PG 8 WC Cell Biology SC Cell Biology GA 574QF UT WOS:000276006000007 PM 20051380 ER PT J AU Barrett, TW Newton, K Koudelka, C Mori, M Radcliffe, L AF Barrett, Thomas W. Newton, Kathleen Koudelka, Caroline Mori, Motomi Radcliffe, LeAnn TI Impact of Combination Medical Therapy on Mortality in Vascular Surgery Patients SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article; Proceedings Paper CT 3rd Annual Perioperative Medicine Meeting CY SEP 11, 2007 CL Cleveland, OH DE mortality; perioperative medicine; vascular surgery; veterans ID PERIOPERATIVE MYOCARDIAL-ISCHEMIA; LONG-TERM MORTALITY; CONVERTING ENZYME-INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; MAJOR NONCARDIAC SURGERY; HIGH-RISK PATIENTS; CARDIOVASCULAR EVENTS; SECONDARY PREVENTION; ANESTHETIC INDUCTION; PROPENSITY SCORE AB BACKGROUND: Th use of beta-blockers or statins has been associated with decreased mortality after noncardiac surgery. There are no prior perioperative studies of concurrent use of other cardioprotective drugs. OBJECTIVE: To ascertain whether combinations of aspirin, beta-blockers, statins, and/or angiotensin-converting enzyme (ACE) inhibitors were associated with decreased mortality 6 months after vascular surgery. PATIENTS AND DESIGN: We performed a retrospective cohort study on the 3020 patients who underwent vascular surgery between January 1998 and March 2005 at 5 regional Veterans Affairs (VA) medical centers. The Cochran-Mantel-Haenszel test was used to assess associations with 6-month all-cause mortality for the combination drug exposures compared to no exposure while adjusting for propensity score. RESULTS: Exposure to all 4 of the study drugs compared to none had a propensity-adjusted relative risk (aRR) of 0.52 (95% confidence interval [CI], 0.26-1.01; P = 0.052), number needed to treat (NNT) 19; 3 drugs vs. none, aRR 0.60 (95% Cl, 0.38-0.95; P = 0.030), NNT 38; 2 drugs vs. none, aRR 0.68 (95% CI, 0.46-0.99; P = 0.043), NNT 170; and 1 drug vs. none, aRR 0.88 (95% CI, 0.63-1.22; P = 0.445). ACE inhibitor exposure was common in all combinations. CONCLUSIONS: Combination use of 2 to 3 study drugs, some of which included ACE inhibitors, was associated with decreased mortality after vascular surgery. Combination use of all 4 study drugs was not statistically significant due to the small number of events in this group. Further prospective studies of combination perioperative aspirin, beta-blockers, statins, and ACE inhibitors are warranted. Journal of Hospital Medicine 2010;5:218-225. (C) 2010 Society of Hospital Medicine. C1 [Barrett, Thomas W.] Portland Vet Affairs VA Med Ctr, Sect Gen Med, Portland, OR USA. [Barrett, Thomas W.] Oregon Hlth & Sci Univ, Div Hosp Med, Portland, OR 97201 USA. [Newton, Kathleen; Mori, Motomi] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97201 USA. [Koudelka, Caroline; Mori, Motomi] Oregon Hlth & Sci Univ, Ctr Biostat Comp & Informat Biol & Med, Portland, OR 97201 USA. [Radcliffe, LeAnn] Portland VA Med Ctr, Portland VA Res Fdn, Portland, OR USA. RP Barrett, TW (reprint author), Portland VAMC P3MED, 3710 SW US VA Hosp Rd, Portland, OR 97207 USA. EM barretth@ohsu.edu FU NCRR NIH HHS [UL1 RR024140] NR 41 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD APR PY 2010 VL 5 IS 4 BP 218 EP 225 DI 10.1002/jhm.614 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 588FJ UT WOS:000277053100005 PM 20394027 ER PT J AU Porcelli, S Brenner, MB Greensteint, JL Balk, SP Terhorst, C Bleicher, PA AF Porcelli, Steven Brenner, Michael B. Greensteint, Julia L. Balk, Steven P. Terhorst, Cox Bleicher, Paul A. TI Recognition of cluster of differentiation 1 antigens by human CD4(-) CD8(-) cytolytic T lymphocytes (Reprinted from Nature vol 341, pg 447-450, 1989) SO JOURNAL OF IMMUNOLOGY LA English DT Reprint ID CELL-RECEPTOR; MONOCLONAL-ANTIBODIES; EXPRESSION; GENES; DELTA; COMPLEX; SPECIFICITY; THYMOCYTES; MOLECULES; HYBRIDOMA AB HUMAN cluster-of-differentiation 1 (CD1) is a family of cell surface glycoproteins of unknown function expressed on immature thymocytes, epidermal Langerhans cells and a subset of B lymphocytes(1-3). Three homologous proteins, CD1a, b and c, have been defined serologically(4), and the CD1 gene locus on human chromosome 1 contains five potential CD1 genes(5). Analysis of the predicted amino-acid sequences of CD1 molecules reveals a low but significant level of homology to major histocompatibility complex (MHC) class I and class II molecules(5,6), and, like MHC class I molecules, CD1 molecules are associated non-covalently with beta 2-microglobulin(7). These structural similarities to known antigen-presenting molecules, together with the expression of CD1 on cells capable of antigen presentation, suggest a role for CD1 molecules in antigen recognition by T cells. Here we demonstrate the specific recognition of CD1a by a CD4(-)CD8(-) alpha beta T-cell receptor (TCR) expressing cytolytic T lymphocyte (CTL) line and the specific recognition of CD1c by a CD4(-)CD8(-) gamma delta TCR CTL line. The interaction of CD1-specific CTLs with CD1(+) target cells appeared to involve the CD3-TCR complex, and did not show evidence of MHC restriction. These results suggest that, for a subset of T cells, CD1 molecules serve a function analogous to that of MHC class I and II molecules. C1 [Porcelli, Steven; Brenner, Michael B.] Brigham & Womens Hosp, Lab Immunochem, Dana Farber Canc Inst, Boston, MA 02115 USA. [Porcelli, Steven; Brenner, Michael B.] Brigham & Womens Hosp, Dept Rheumatol & Immunol, Boston, MA 02115 USA. [Balk, Steven P.; Terhorst, Cox; Bleicher, Paul A.] Dana Farber Canc Inst, Lab Mol Immunol, Boston, MA 02115 USA. [Bleicher, Paul A.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Terhorst, Cox] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Balk, Steven P.] Beth Israel Hosp, Dept Hematol & Oncol, Boston, MA 02115 USA. [Greensteint, Julia L.] ImmuLog Pharmaceut Corp, Cambridge, MA 02139 USA. RP Porcelli, S (reprint author), Brigham & Womens Hosp, Lab Immunochem, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI015066, R37 AI017651]; NIDDK NIH HHS [R01 DK052510] NR 33 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 IS 7 BP 3306 EP 3309 PG 4 WC Immunology SC Immunology GA 573PV UT WOS:000275927600002 PM 20304831 ER PT J AU Wang, H Wu, XJ Wang, Y Oldenborg, PA Yang, YG AF Wang, Hui Wu, Xiaojian Wang, Yuantao Oldenborg, Per-Arne Yang, Yong-Guang TI CD47 Is Required for Suppression of Allograft Rejection by Donor-Specific Transfusion SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8(+) T-CELLS; DENDRITIC CELLS; BONE-MARROW; TOLERANCE; MECHANISMS; ANTIGENS; SURVIVAL; TRANSPLANTATION; PHAGOCYTOSIS; LYMPHOCYTES AB CD47 is a ligand of the inhibitory receptor, signal regulatory protein (SIRP)alpha, and its interaction with SIRP alpha on macrophages prevents phagocytosis of autologous hematopoietic cells. CD47-SIRP alpha signaling also regulates dendritic cell (DC) endocytosis, activation, and maturation. In this study, we show that CD47 expression on donor cells plays an important role in suppression of allograft rejection by donor-specific transfusion (DST). DST was performed by i.v. injection of splenocytes from C57BL/6 donors into MHC class I-disparate brut mice 7 d prior to donor skin grafting. Administration of wild-type (WT) C57BL/6 donor splenocytes markedly prolonged donor skin survival in bm1 mouse recipients. In contrast, bm1 mice receiving DST from CD47 knockout (KO) donors showed no inhibition or even acceleration of donor skin graft rejection compared with non-DST control (naive) brut mice. T cells from bm1 mice receiving CD47 KO, but not WT, DST exhibited strong anti-donor responses. The ability of DST to suppress alloresponses was positively correlated with the density of CD47 molecules on donor cells, as CD47(+/-) DST was able to prolonged donor skin survival, but to a significantly less extent than WT DST. Furthermore, DCs from CD47 KO, but not WT, DST recipients showed rapid activation and contributed to donor skin rejection. These results show for the first time that CD47 on donor cells is required to repress recipient DC activation and suppress allograft rejection after DST, and suggest CD47 as a potential target for facilitating the induction of transplant tolerance. The Journal of Immunology, 2010, 184: 3401-3407. C1 [Wang, Hui; Wu, Xiaojian; Wang, Yuantao; Yang, Yong-Guang] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Wu, Xiaojian] Sun Yat Sen Univ, Dept Surg, Affiliated Hosp 6, Guangzhou 510275, Guangdong, Peoples R China. [Wang, Yuantao] Jilin Univ, Hosp 1, Changchun 130023, Peoples R China. [Oldenborg, Per-Arne] Sect Histol & Cell Biol, Dept Integrat Med Biol, Umea, Sweden. RP Yang, YG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH East,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu FU National Institutes of Health and National Institute of Allergy and Infectious Diseases [RO1 AI064569]; American Heart Association/National Clinical Research Program Scientist Development [0930361N] FX This work was supported by National Institutes of Health and National Institute of Allergy and Infectious Diseases Grant RO1 AI064569 and American Heart Association/National Clinical Research Program Scientist Development Grant 0930361N. NR 31 TC 13 Z9 15 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 1 PY 2010 VL 184 IS 7 BP 3401 EP 3407 DI 10.4049/jimmunol.0901550 PG 7 WC Immunology SC Immunology GA 573PV UT WOS:000275927600016 PM 20208011 ER PT J AU Bai, XY Kim, SH Azam, T McGibney, MT Huang, H Dinarello, CA Chan, ED AF Bai, Xiyuan Kim, Soo-Hyun Azam, Tania McGibney, Mischa T. Huang, Hua Dinarello, Charles A. Chan, Edward D. TI IL-32 Is a Host Protective Cytokine against Mycobacterium tuberculosis in Differentiated THP-1 Human Macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; NITRIC-OXIDE SYNTHASE; CASPASE-INDEPENDENT PATHWAY; PHAGOSOME-LYSOSOME FUSION; GROWTH-FACTOR-BETA; T-CELLS; VIRUS-INFECTION; BALB/C MICE; TNF-ALPHA; PROINFLAMMATORY CYTOKINE AB Macrophages provide a first line of defense against Mycobacterium tuberculosis. However, in instances where macrophage activation for killing is suboptimal, M. tuberculosis is capable of surviving intracellularly. IL-32 is a recently described cytokine induced by M. tuberculosis in a variety of cell types including human monocytes and macrophages. In this study, we investigated the biological significance of IL-32 in an in vitro model of M. tuberculosis infection in differentiated THP-1 human macrophages in which IL-32 expression was silenced using stable expression of short hairpin RNA (shRNA). Inhibition of endogenous IL-32 production in THP-1 cells that express one of three distinct shRNA-IL-32 constructs significantly decreased M. tuberculosis induction of TNF-alpha by similar to 60%, IL-10 by 30-60%, and IL-8 by 40-50% and concomitantly increased the number of cell-associated M. tuberculosis bacteria compared with THP-1 cells stably expressing a scrambled shRNA. In THP-1 cells infected with M. tuberculosis and stimulated with rIL-32, a greater level of apoptosis was observed compared with that with M. tuberculosis infection alone. Obversely, there was significant abrogation of apoptosis induced by M. tuberculosis and a concomitant decrease in caspase-3 activation in cells depleted of endogenous IL-32. rIL-32 gamma significantly reduced the number of viable intracellular M. tuberculosis bacteria, which was modestly but significantly abrogated with a caspase-3 inhibitor. We conclude that IL-32 plays a host defense role against M. tuberculosis in differentiated THP-1 human macrophages. The Journal of Immunology, 2010,184: 3830-3840. C1 [Chan, Edward D.] Natl Jewish Hlth, Dept Med, Div Mycobacterial & Resp Infect, Denver, CO 80206 USA. [Bai, Xiyuan; McGibney, Mischa T.; Chan, Edward D.] Univ Colorado, Anschutz Med Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80045 USA. [Azam, Tania; Dinarello, Charles A.] Univ Colorado, Anschutz Med Ctr, Div Infect Dis, Denver, CO 80045 USA. [Huang, Hua] Natl Jewish Hlth, Dept Immunol, Denver, CO 80206 USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. [Kim, Soo-Hyun] Konkuk Univ, Inst Biomed Sci & Technol, Lab Cytokine Immunol, Seoul, South Korea. RP Chan, ED (reprint author), Natl Jewish Hlth, Dept Med, Div Mycobacterial & Resp Infect, Neustadt Bldg D509,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org FU Office of Research and Development, Veterans Health Administration, Department of Veterans Affairs; National Institutes of Health [AI15614] FX This work was supported in part by the Office of Research and Development, Veterans Health Administration, Department of Veterans Affairs (to E.D.C.) and National Institutes of Health Grant AI15614 (to C.A.D.). NR 85 TC 48 Z9 52 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 IS 7 BP 3830 EP 3840 DI 10.4049/jimmunol.0901913 PG 11 WC Immunology SC Immunology GA 573PV UT WOS:000275927600061 PM 20190143 ER PT J AU Niland, B Miklossy, G Banki, K Biddison, WE Casciola-Rosen, L Rosen, A Martinvalet, D Lieberman, J Perl, A AF Niland, Brian Miklossy, Gabriella Banki, Katalin Biddison, William E. Casciola-Rosen, Livia Rosen, Antony Martinvalet, Denis Lieberman, Judy Perl, Andras TI Cleavage of Transaldolase by Granzyme B Causes the Loss of Enzymatic Activity with Retention of Antigenicity for Multiple Sclerosis Patients SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; CD8(+) T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; CLONAL EXPANSIONS; INDUCED APOPTOSIS; MOUSE MODELS; BRAIN; OLIGODENDROCYTE; AUTOANTIBODIES AB Multiple sclerosis (MS) is an autoimmune demyelinating disease of the CNS resulting from a progressive loss of oligodendrocytes. Transaldolase (TAL) is expressed at selectively high levels in oligodendrocytes of the brain, and postmortem sections show concurrent loss of myelin basic protein and TAL from sites of demyelination. Infiltrating CD8(+) CTLs are thought to play a key role in oligodendrocyte cell death. Cleavage by granzyme B (GrB) is predictive for autoantigenicity of self-proteins, thereby further implicating CTL-induced death in the initiation and propagation of autoimmunity. The precursor frequency and CTL activity of HLA-A2-restricted TAL 168-176-specific CD8(+) T cells is increased in MS patients. In this paper, we show that TAL, but not myelin basic protein, is specifically cleaved by human GrB. The recognition site of GrB that resulted in the cleavage of a dominant TAL fragment was mapped to a VVAD motif at aa residue 27 by N-terminal sequencing and confirmed by site-directed mutagenesis. The major C-terminal GrB cleavage product, residues 28-337, had no enzymatic activity but retained the antigenicity of full-length TAL, effectively stimulating the proliferation and CTL, activity of PBMCs and of CD8(+) T cell lines from patients with MS. Sera of MS patients exhibited similar binding affinity to wild-type and GrB-cleaved TAL. Because GrB mediates the killing of target cells and cleavage by GrB is predictive of autoantigen status of self proteins, GrB-cleaved TAL-specific T cell-mediated cytotoxicity may contribute to the progressive destruction of oligodendrocytes in patients with MS. The journal of Immunology,2010, 184: 4025-4032. C1 [Niland, Brian; Miklossy, Gabriella; Perl, Andras] SUNY Syracuse, Dept Med, Coll Med, Syracuse, NY 13210 USA. [Banki, Katalin] SUNY Syracuse, Dept Pathol, Coll Med, Syracuse, NY 13210 USA. [Perl, Andras] SUNY Syracuse, Dept Microbiol, Coll Med, Syracuse, NY 13210 USA. [Biddison, William E.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Casciola-Rosen, Livia; Rosen, Antony] Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA. [Martinvalet, Denis; Lieberman, Judy] Harvard Univ, Ctr Blood Res, Boston, MA 02115 USA. RP Perl, A (reprint author), SUNY Syracuse, Dept Med, Coll Med, 750 E Adams St, Syracuse, NY 13210 USA. EM perla@upstate.edu RI Lieberman, Judy/A-2717-2015; OI Perl, Andras/0000-0002-5017-1348 FU National Institutes of Health [RO1 DK 49221]; National Multiple Sclerosis Society [RG 2466] FX This work was supported in part by Grant RO1 DK 49221 from the National Institutes of Health and Grant RG 2466 from the National Multiple Sclerosis Society. NR 66 TC 7 Z9 7 U1 1 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 1 PY 2010 VL 184 IS 7 BP 4025 EP 4032 DI 10.4049/jimmunol.0804174 PG 8 WC Immunology SC Immunology GA 573PV UT WOS:000275927600081 PM 20194725 ER PT J AU Benayides, A Fernandez, E Sharp, Z Strong, R Kraig, E AF Benayides, Adriana Fernandez, Elizabeth Sharp, Z. Strong, Randy Kraig, Ellen TI Treg and rapamycin effects on humoral immunity in young and old mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Benayides, Adriana; Fernandez, Elizabeth; Sharp, Z.; Strong, Randy; Kraig, Ellen] UTHSCSA, Micro & Immunol, San Antonio, TX USA. [Fernandez, Elizabeth] Barshop Inst Longev & Aging Studies, San Antonio, TX USA. [Strong, Randy] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 84.12 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301224 ER PT J AU Bu, X Ballesterous, A Chim, YL Santiago, C Lee, HH Umetsu, D Casasnovas, J DeKruyff, R Freeman, G AF Bu, Xia Ballesterous, Angela Chim, Yee-Ling Santiago, Cesar Lee, Hyun-Hee Umetsu, Dale Casasnovas, Jose DeKruyff, Rosemarie Freeman, Gordon TI TIM-3 is a receptor for phosphatidylserine and allelic variants differentially mediate uptake of apoptotic cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Bu, Xia; Freeman, Gordon] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Ballesterous, Angela; Santiago, Cesar; Casasnovas, Jose] CSIC, Ctr Nacl Biotecnol, Madrid, Spain. [Chim, Yee-Ling; Lee, Hyun-Hee; Umetsu, Dale; DeKruyff, Rosemarie] Harvard Med Sch, Childrens Hosp Boston, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 130.41 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303108 ER PT J AU Bu, X Zhu, BG Umetsu, D DeKruyff, R Freeman, G AF Bu, Xia Zhu, Baogong Umetsu, Dale DeKruyff, Rosemarie Freeman, Gordon TI TIM-4 mediated phagocytosis of apoptotic cells induces regulatory cytokine secretion by mouse peritoneal macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Bu, Xia; Zhu, Baogong; Freeman, Gordon] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Umetsu, Dale; DeKruyff, Rosemarie] Harvard Med Sch, Childrens Hosp Boston, Boston, MA USA. NR 0 TC 1 Z9 1 U1 2 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 136.47 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304031 ER PT J AU Call, M Wucherpfennig, K Chou, J AF Call, Matthew Wucherpfennig, Kai Chou, James TI Structural basis of DAP12-associated intramembrane immunoreceptor assembly. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Call, Matthew; Chou, James] Harvard Med Sch, Biol Chem & Mol Pharmacol, Boston, MA USA. [Wucherpfennig, Kai] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wucherpfennig, Kai] Harvard Med Sch, Neurol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 138.16 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304070 ER PT J AU Call, M Xing, XC Cuny, G Stein, R Wucherpfennig, K AF Call, Melissa Xing, Xuechao Cuny, Gregory Stein, Ross Wucherpfennig, Kai TI Small molecule enhancers of peptide binding to MHC class II: Implications for DM function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Call, Melissa; Wucherpfennig, Kai] Dana Farber Canc Inst, Canc Immunol & AIDS, Boston, MA 02115 USA. [Wucherpfennig, Kai] Harvard Med Sch, Boston, MA USA. [Xing, Xuechao; Cuny, Gregory; Stein, Ross] Harvard Neurodiscovery Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 130.40 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304284 ER PT J AU Callendret, B Bowen, D Fuller, M Eccleston, H Rutckiewitz, J Hasselschwert, D Freeman, G Walker, C AF Callendret, Benoit Bowen, David Fuller, Michael Eccleston, Heather Rutckiewitz, Jennifer Hasselschwert, Dana Freeman, Gordon Walker, Christopher TI Exhaustion of intra-hepatic CD8+T cells targeting intact and escaped MHC class I epitopes in chronic phase of hepatitis C virus infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Callendret, Benoit; Bowen, David; Fuller, Michael; Eccleston, Heather; Rutckiewitz, Jennifer; Walker, Christopher] Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, Columbus, OH USA. [Hasselschwert, Dana] New Iberia Res Ctr, New Iberia, LA USA. [Freeman, Gordon] Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 39.20 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300171 ER PT J AU Chang, H Biswas, S Tallarico, A Sarkis, P Marasco, W AF Chang, Hong Biswas, Subhabrata Tallarico, Aimee Sarkis, Phuong Marasco, Wayne TI Analysis of human immunoglobulin gene repertoire in NOD/scid IL2R gamma null mice engrafted with human cord blood derived hematopoietic stem cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chang, Hong; Biswas, Subhabrata; Tallarico, Aimee; Sarkis, Phuong; Marasco, Wayne] Harvard Med Sch, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA USA. [Chang, Hong; Biswas, Subhabrata; Tallarico, Aimee; Sarkis, Phuong; Marasco, Wayne] Harvard Med Sch, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.14 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300042 ER PT J AU Clark, AM Young, MR AF Clark, Anna-Maria Young, M. Rita TI Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate results in an increase in CD4+and CD8+T cells and a decrease in Foxp3+cells in tongues of mice bearing carcinogen induced premalignant oral lesions. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Clark, Anna-Maria; Young, M. Rita] Med Univ South Carolina, Microbiol & Immunol, Charleston, SC USA. [Clark, Anna-Maria; Young, M. Rita] Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 131.24 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303175 ER PT J AU Ding, YN Wang, J Xie, ST Hsu, HC Mountz, J AF Ding, Yanna Wang, John Xie, Shutao Hsu, Hui-Chen Mountz, John TI Nuclear expression of CXCR5 is asscociated with expansion of spleen follicular T helper cells in autoimmune BXD2 mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ding, Yanna; Wang, John; Xie, Shutao; Hsu, Hui-Chen; Mountz, John] Univ Alabama Birmingham, Birmingham, AL USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 143.30 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304165 ER PT J AU Erlebacher, A de Lafaille, MC Lafaille, J Carroll, M McCloskey, M AF Erlebacher, Adrian de Lafaille, Maria Curotto Lafaille, Juan Carroll, Michael McCloskey, Megan TI Regulation of CD8 T cell responses by follicular dendritic cell-bound antigen SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Erlebacher, Adrian; de Lafaille, Maria Curotto; Lafaille, Juan; McCloskey, Megan] NYU, Sch Med, Pathol, New York, NY USA. [de Lafaille, Maria Curotto; Lafaille, Juan] Skirball Inst Biomol Med, New York, NY USA. [Carroll, Michael] Harvard Med Sch, Immune Dis Inst, Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 98.17 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302299 ER PT J AU Fan, J Li, YH Xiang, M Billiar, T Wilson, M AF Fan, Jie Li, Yuehua Xiang, Meng Billiar, Timothy Wilson, Mark TI Hemorrhagic shock primes for IL-1 beta processing: role of upregulated TLR2 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Fan, Jie; Li, Yuehua; Xiang, Meng; Billiar, Timothy; Wilson, Mark] Univ Pittsburgh, Surg, Pittsburgh, PA USA. [Fan, Jie; Wilson, Mark] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 136.1 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304004 ER PT J AU Francisco, L Salinas, V Brown, K Vanguri, V Freeman, G Kuchroo, V Sharpe, A AF Francisco, Loise Salinas, Victor Brown, Keturah Vanguri, Vijay Freeman, Gordon Kuchroo, Vijay Sharpe, Arlene TI The PD-Ligand Pathway regulates the development, maintenance and function of induced regulatory T cells in vitro and in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Francisco, Loise; Brown, Keturah; Vanguri, Vijay; Kuchroo, Vijay; Sharpe, Arlene] Harvard Med Sch, Boston, MA USA. [Francisco, Loise] Brigham & Womens Hosp, Boston, MA 02115 USA. [Salinas, Victor] Harvard Univ, Cambridge, MA 02138 USA. [Freeman, Gordon] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kuchroo, Vijay] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 49.16 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301083 ER PT J AU Lear, C Zeitler, C Karpell, M Spear, G Olinger, G AF Lear, Calli Zeitler, Corinne Karpell, Marshall Spear, Gregory Olinger, Gene TI A Novel L-Ficolin-Mannose Binding Lectin Chimeric Molecule With Enhanced Activity Against Lethal Viral Infections SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lear, Calli; Zeitler, Corinne] USAMRIID, Ft Detrick, MD USA. [Karpell, Marshall; Olinger, Gene] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Spear, Gregory] Rush Univ, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 39.33 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300177 ER PT J AU Li, H Wu, Q Yang, PA Wang, J Kolls, J Hsu, HC Mountz, J AF Li, Hao Wu, Qi Yang, PingAr Wang, John Kolls, Jay Hsu, Hui-chen Mountz, John TI Collaborative Effects of IL-17 and IL-23 in Deletion of Antigen Stimulated CD4+CD8+Double Positive Thymocytes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Li, Hao; Wu, Qi; Yang, PingAr; Wang, John; Hsu, Hui-chen; Mountz, John] Univ Alabama Birmingham, Birmingham, AL USA. [Kolls, Jay] Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 143.17 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304155 ER PT J AU Lin, PY Sun, L Wierman, M Tekmal, R Pierce, A Daniel, B Curiel, T AF Lin, Pei-Yi Sun, Lishi Wierman, Margaret Tekmal, Rajeshwar Pierce, Anson Daniel, Benjamin Curiel, Tyler TI Sex-related differences in regulatory T cell function are estrogen and B7-H1 dependent SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lin, Pei-Yi; Sun, Lishi; Tekmal, Rajeshwar; Pierce, Anson; Daniel, Benjamin; Curiel, Tyler] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wierman, Margaret] Univ Colorado, Aurora, CO USA. [Pierce, Anson] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 143.53 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304159 ER PT J AU Pinner, S Mourao-Sa, D Turley, S AF Pinner, Sophie Mourao-Sa, Diego Turley, Shannon TI Podoplanin interactions with CLEC-2 regulate dendritic cell migration SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pinner, Sophie; Turley, Shannon] Dana Farber Canc Inst, Canc Immunol & AIDS, Boston, MA 02115 USA. [Mourao-Sa, Diego] Canc Res UK London Res Inst, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 44.4 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300296 ER PT J AU Shamri, R Melo, R Weller, P AF Shamri, Revital Melo, Rossana Weller, Peter TI CCR3-mediated degranulation and eosinophil-associated RNases secretion from murine eosinophils; capacity of intact cells and free granules SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Shamri, Revital; Melo, Rossana; Weller, Peter] Beth Isreal Deaconess Med Ctr, Med, Boston, MA USA. [Melo, Rossana] Univ Fed Juiz de Fora, Juiz De Fora, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 86.21 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301269 ER PT J AU Stephen, T Wilson, B Laufer, T AF Stephen, Tom Wilson, Bridget Laufer, Terri TI Reorganizing the signaling molecules in CD4+T cells by TCR-MHC class II interactions in the thymic medulla prevents T cell hyperactivation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Stephen, Tom; Laufer, Terri] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Wilson, Bridget] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Laufer, Terri] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 50.1 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301115 ER PT J AU Turley, S Rubinstein, M Goldrath, A Elpek, K AF Turley, Shannon Rubinstein, Mark Goldrath, Ananda Elpek, Kutlu TI Long-term cytokine therapy with IL-15/IL-15R alpha complexes leads to impaired NK cell function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Turley, Shannon; Elpek, Kutlu] Dana Farber Canc Inst, Canc Immunol & AIDS, Boston, MA 02115 USA. [Rubinstein, Mark; Goldrath, Ananda] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 131.11 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303174 ER PT J AU West, E Ha, SJ Tan, W Jin, HT Freeman, G Smith, K Ahmed, R AF West, Erin Ha, Sang-Jun Tan, Wendy Jin, Hyun-Tak Freeman, Gordon Smith, Kendall Ahmed, Rafi TI IL-2 therapy synergizes with PD-L1 blockade to rescue exhausted CD8+T cells during chronic viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [West, Erin; Ha, Sang-Jun; Tan, Wendy; Jin, Hyun-Tak; Ahmed, Rafi] Emory Univ, Atlanta, GA 30322 USA. [Freeman, Gordon] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, Kendall] Cornell Univ, Ithaca, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 137.24 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304043 ER PT J AU Zlotoff, D Sambandam, A Logan, T Bell, J Schwarz, B Bhandoola, A AF Zlotoff, Daniel Sambandam, Arivazhagan Logan, T. Bell, J. Schwarz, Benjamin Bhandoola, Avinash TI Identifying chemokine receptor signals required for thymic settling SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zlotoff, Daniel; Sambandam, Arivazhagan; Logan, T.; Bell, J.; Bhandoola, Avinash] Univ Penn, Pathol & Lab Med, Philadelphia, PA 19104 USA. [Schwarz, Benjamin] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.26 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300063 ER PT J AU Jensen, JK Ueland, T Atar, D Gullestad, L Mickley, H Aukrust, P Januzzi, JL AF Jensen, J. K. Ueland, T. Atar, D. Gullestad, L. Mickley, H. Aukrust, P. Januzzi, J. L. TI Osteoprotegerin concentrations and prognosis in acute ischaemic stroke SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE stroke ID ACUTE CORONARY SYNDROMES; SERUM OSTEOPROTEGERIN; ARTERY-DISEASE; BONE-DENSITY; PLASMA; CALCIFICATION; ATHEROSCLEROSIS; ACTIVATION; MORTALITY; ELEVATION AB Jensen JK, Ueland T, Atar D, Gullestad L, Mickley H, Aukrust P, Januzzi JL (Odense University Hospital, Denmark; Rikshospitalet, Oslo, Norway; Massachusetts General Hospital, USA). Osteoprotegerin concentrations and prognosis in acute ischaemic stroke. J Intern Med 2010; 267: 410-417. Aim. Concentrations of osteoprotegerin (OPG) have been associated with the presence of vascular and cardiovascular diseases, but the knowledge of this marker in the setting of ischaemic stroke is limited. Methods and results. In 244 patients with acute ischaemic stroke (age: 69 +/- 13 years), samples of OPG were obtained serially from presentation to day 5. Patients with overt ischaemic heart disease and atrial fibrillation were excluded. The patients were followed for 47 months, with all-cause mortality as the sole end-point. Multivariable predictors of OPG values at presentation included haemoglobin (T = -2.82; P = 0.005), creatinine (T = 4.56; P < 0.001), age (T = 9.66; P < 0.001), active smoking (T = 2.25; P = 0.025) and pulse rate (T = 3.23; P = 0.001). At follow-up 72 patients (29%) had died. Patients with OPG < 2945 pg mL-1 at baseline had a significantly improved survival rate on univariate analysis (P < 0.0001); other time-points did not add further prognostic information. In multivariate analysis, after adjustment for age, stroke severity, C-reactive protein levels, troponin T levels, heart and renal failure concentrations of OPG independently predicted long-term mortality after stroke (adjusted hazard ratio, 2.3; 95% CI: 1.1 to 4.9; P = 0.024). Conclusion. Osteoprotegerin concentrations measured at admission of acute ischaemic stroke are associated with long-term mortality. C1 [Jensen, J. K.; Mickley, H.] Odense Univ Hosp, Dept Cardiol, DK-5000 Odense C, Denmark. [Atar, D.] Univ Oslo, Fac Med, N-0316 Oslo, Norway. [Atar, D.] Univ Oslo, Aker Univ Hosp, Div Cardiol, N-0316 Oslo, Norway. [Gullestad, L.] Univ Oslo, Rikshosp, Dept Cardiovasc Med, N-0027 Oslo, Norway. [Januzzi, J. L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Jensen, JK (reprint author), Odense Univ Hosp, Dept Cardiol, DK-5000 Odense C, Denmark. EM jesperkjensen@dadlnet.dk FU Danish Heart Foundation; Danish Heart Foundation, Copenhagen; Balson Scholar Fund FX JKJ was supported by a grant from the Danish Heart Foundation, Copenhagen. JLJ was supported in part by the Balson Scholar Fund. NR 25 TC 27 Z9 29 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD APR PY 2010 VL 267 IS 4 BP 410 EP 417 DI 10.1111/j.1365-2796.2009.02163.x PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 568JM UT WOS:000275518600008 PM 19895657 ER PT J AU Jensen, JK Aukrust, P Januzzi, JL AF Jensen, J. K. Aukrust, P. Januzzi, J. L. TI Osteoprotegerin and acute ischaemic stroke: reply SO JOURNAL OF INTERNAL MEDICINE LA English DT Letter ID PLASMA OSTEOPROTEGERIN C1 [Jensen, J. K.] Odense Univ Hosp, Dept Cardiol, Odense, Denmark. [Aukrust, P.] Univ Oslo, Rikshosp, Internal Med Res Inst, N-0027 Oslo, Norway. [Januzzi, J. L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Jensen, JK (reprint author), Odense Univ Hosp, Dept Cardiol, Odense, Denmark. EM jesperkjensen@dadlnet.dk NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD APR PY 2010 VL 267 IS 4 BP 437 EP 437 DI 10.1111/j.1365-2796.2009.02170.x PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 568JM UT WOS:000275518600011 ER PT J AU Chock, M Goreshi, R Keiser, E Werth, VP Chung, L Florentino, D AF Chock, M. Goreshi, R. Keiser, E. Werth, V. P. Chung, L. Florentino, D. TI Quantitative assessment of disease severity in dermatomyositis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Chock, M.; Keiser, E.; Chung, L.; Florentino, D.] Stanford Univ, Stanford, CA 94305 USA. [Goreshi, R.; Werth, V. P.] Univ Penn, Philadelphia, PA 19104 USA. [Goreshi, R.; Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA 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 APR PY 2010 VL 130 SU 1 MA 299 BP S50 EP S50 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100297 ER PT J AU Clark, R Watanabe, R Fisher, DC Walsh, M Tawa, M Campbell, I Martin, F Adams, N Kupper, TS AF Clark, R. Watanabe, R. Fisher, D. C. Walsh, M. Tawa, M. Campbell, I. Martin, F. Adams, N. Kupper, T. S. TI Low dose alemtuzumab (LDA) depletes malignant central memory T cells but spares normal skin resident effector memory T cells in leukemic CTCL SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Clark, R.; Watanabe, R.; Fisher, D. C.; Walsh, M.; Tawa, M.; Campbell, I.; Martin, F.; Adams, N.; Kupper, T. S.] Dana Farber Brigham & Womens Canc Ctr, 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 APR PY 2010 VL 130 SU 1 MA 278 BP S47 EP S47 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100280 ER PT J AU de Long, A Pena-Cruz, V Cheng, T Moody, B AF de Long, A. Pena-Cruz, V. Cheng, T. Moody, B. TI The human T cell repertoire contains CD1a autoreactive T cells that home to the skin and modulate keratinocytes through interleukin-22 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [de Long, A.; Cheng, T.; Moody, B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Pena-Cruz, V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [de Long, A.; Pena-Cruz, V.; Cheng, T.; Moody, B.] Harvard Univ, Sch Med, Boston, MA 02115 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 APR PY 2010 VL 130 SU 1 MA 720 BP S120 EP S120 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100718 ER PT J AU Enshell-Sejffers, D Kashiwagi, M Morgan, BA AF Enshell-Sejffers, D. Kashiwagi, M. Morgan, B. A. TI Inductive signaling from the dermal papilla of the hair follicle SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Enshell-Sejffers, D.; Kashiwagi, M.; Morgan, B. A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Enshell-Sejffers, D.; Kashiwagi, M.; Morgan, B. A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 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 APR PY 2010 VL 130 SU 1 MA 647 BP S108 EP S108 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100643 ER PT J AU Kawasumi, M Sloan, H Bradner, J Nghiem, P AF Kawasumi, M. Sloan, H. Bradner, J. Nghiem, P. TI Novel ATM/ATR pathway inhibitors sensitize p53-deficient cells to DNA-damaging agents in vitro and in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Kawasumi, M.; Sloan, H.; Nghiem, P.] Univ Washington, Seattle, WA 98195 USA. [Bradner, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 180 BP S30 EP S30 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100180 ER PT J AU Kim, S Meier, B Schatton, T Wilson, B Zhan, Q Loh, YH Daley, GQ Sayegh, MH Ziouta, Y Ganns, C Scharffetter-Kochanek, K Murphy, GF Frank, MH Frank, NY AF Kim, S. Meier, B. Schatton, T. Wilson, B. Zhan, Q. Loh, Y. H. Daley, G. Q. Sayegh, M. H. Ziouta, Y. Ganns, C. Scharffetter-Kochanek, K. Murphy, G. F. Frank, M. H. Frank, N. Y. TI Identification of human ABCB5(+) dermal progenitor cells with multipotent differentiation plasticity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Kim, S.; Schatton, T.; Wilson, B.; Loh, Y. H.; Daley, G. Q.; Sayegh, M. H.; Frank, M. H.; Frank, N. Y.] Childrens Hosp, Boston, MA 02115 USA. [Meier, B.; Scharffetter-Kochanek, K.] Univ Ulm, Ulm, Germany. [Zhan, Q.; Sayegh, M. H.; Murphy, G. F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ziouta, Y.; Ganns, C.] TiCeBa GmbH, Heidelberg, Germany. [Murphy, G. F.; Frank, M. H.; Frank, N. Y.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 1 Z9 1 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 APR PY 2010 VL 130 SU 1 MA 642 BP S107 EP S107 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100640 ER PT J AU Lerner, EA Sun, Y Shimada, SG Sikand, P LaMotte, RH Reddy, VB AF Lerner, E. A. Sun, Y. Shimada, S. G. Sikand, P. LaMotte, R. H. Reddy, V. B. TI Cathepsin S is a cysteine protease, elicits itch and signals via protease-activated receptors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Lerner, E. A.; Sun, Y.; Reddy, V. B.] Massachusetts Gen Hosp, Dematol Cutaneous Biol Res Ctr, Charlestown, MA USA. [Shimada, S. G.; Sikand, P.; LaMotte, R. H.] Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06510 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 APR PY 2010 VL 130 SU 1 MA 598 BP S100 EP S100 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100598 ER PT J AU Liang, X Wagers, A Clark, R Liu, L Fuhlbrigge, R Kupper, T AF Liang, X. Wagers, A. Clark, R. Liu, L. Fuhlbrigge, R. Kupper, T. TI Effector memory T cells persist long term in the skin, and their recirculation into blood is limited SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Liang, X.; Clark, R.; Liu, L.; Fuhlbrigge, R.; Kupper, T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wagers, A.] Joslin Diabet Ctr, Boston, MA 02215 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 APR PY 2010 VL 130 SU 1 MA 712 BP S119 EP S119 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100711 ER PT J AU Lima, XT Lima, HC Kimball, AB AF Lima, X. T. Lima, H. C. Kimball, A. B. TI A cross-sectional study of skin carotenoid levels in adult patients with psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Lima, X. T.; Lima, H. C.; Kimball, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Lima, Hermenio/A-1616-2010; Lima, Hermenio/G-5379-2010 OI Lima, Hermenio/0000-0003-0950-3731 NR 0 TC 1 Z9 1 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 APR PY 2010 VL 130 SU 1 MA 262 BP S44 EP S44 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100263 ER PT J AU Lima, XT Minnillo, R Kimball, AB AF Lima, X. T. Minnillo, R. Kimball, A. B. TI Psoriasis prevalence among the 2009 melanoma/skin cancer screening patients SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Lima, X. T.; Kimball, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Minnillo, R.] Soc Investigat Dermatol, Cleveland, OH 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 APR PY 2010 VL 130 SU 1 MA 269 BP S45 EP S45 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100267 ER PT J AU Mao, X Sano, Y Park, JM Payne, AS AF Mao, X. Sano, Y. Park, J. M. Payne, A. S. TI p38 alpha MAPK is not required for the loss of intercellular adhesion in pemphigus vulgaris SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Mao, X.; Payne, A. S.] Univ Penn, Philadelphia, PA 19104 USA. [Sano, Y.; Park, J. M.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 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 APR PY 2010 VL 130 SU 1 MA 212 BP S36 EP S36 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100214 ER PT J AU Nabatian, A Bashir, MM Werth, V AF Nabatian, A. Bashir, M. M. Werth, V. P. TI Immunologic actions of glycosaminoglycans in cutaneous lupus erythematosus & dermatomyositis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Nabatian, A.; Bashir, M. M.; Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Nabatian, A.; Bashir, M. M.; Werth, V. P.] Univ Penn, Philadelphia, PA 19104 USA. [Nabatian, A.] UMDNJ, Robert Wood Johnson Med Sch, New Brunswick, 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 APR PY 2010 VL 130 SU 1 MA 044 BP S8 EP S8 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100047 ER PT J AU Paliwal, A Gruber, JD O'Hara, JA Pogue, BW Hasan, T Maytin, EV AF Paliwal, A. Gruber, J. D. O'Hara, J. A. Pogue, B. W. Hasan, T. Maytin, E. V. TI Development and validation of a high frequency ultrasound-guided fluorescence tomography system to improve targeting of photodynamic therapy of skin tumors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Paliwal, A.; Hasan, T.; Maytin, E. V.] Cleveland Clin Fdn, Lerner Coll Med, Cleveland Clin, Cleveland, OH 44195 USA. [Gruber, J. D.; O'Hara, J. A.; Pogue, B. W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Pogue, B. W.; Maytin, E. V.] Massachusetts Gen Hosp, Harvard Med Sch, Wellman Ctr Photomed, Boston, 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 APR PY 2010 VL 130 SU 1 MA 784 BP S131 EP S131 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100783 ER PT J AU Sharma, SD Katiyar, SK AF Sharma, S. D. Katiyar, S. K. TI Obesity exacerbates UVB radiation-induced inflammation and cell survival signals in UVB-irradiated mouse skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Sharma, S. D.; Katiyar, S. K.] Univ Alabama, Birmingham, AL USA. [Katiyar, S. K.] Birmingham VA Med Ctr, Birmingham, AL 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 APR PY 2010 VL 130 SU 1 MA 768 BP S128 EP S128 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100766 ER PT J AU Sun, Y Reddy, VB Lerner, EA AF Sun, Y. Reddy, V. B. Lerner, E. A. TI Mechanisms of pruritus: Potential relationship between IL-31, IFN-gamma, cathepsins and protease-activated receptors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Sun, Y.; Reddy, V. B.; Lerner, E. A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 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 APR PY 2010 VL 130 SU 1 MA 116 BP S20 EP S20 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100119 ER PT J AU Tsao, S Yao, M Henry, FP Tsao, H Zhao, Y Kochevar, J Redmond, R Kochevar, I AF Tsao, S. Yao, M. Henry, F. P. Tsao, H. Zhao, Y. Kochevar, J. Redmond, R. Kochevar, I. TI A phase I/II trial of photoactivated tissue bonding ("nanosuturing") for excisional wound closure SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Tsao, S.; Yao, M.; Henry, F. P.; Tsao, H.; Zhao, Y.; Kochevar, J.; Redmond, R.; Kochevar, I.] Massachusetts Gen Hosp, Wellman Ctr Photomed Dermatol, 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 APR PY 2010 VL 130 SU 1 MA 252 BP S42 EP S42 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100252 ER PT J AU Vaid, M Nandakumar, V Elmets, CA Katiyar, SK AF Vaid, M. Nandakumar, V. Elmets, C. A. Katiyar, S. K. TI (-)-Epigallocatechin-3-gallate reactivates silenced tumor suppressor gene by modifying DNA methylation and histone acetylation patterns in human epidermoid carcinoma cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Vaid, M.; Nandakumar, V.; Elmets, C. A.; Katiyar, S. K.] Univ Alabama, Birmingham, AL USA. [Elmets, C. A.; Katiyar, S. K.] Birmingham VA Med Ctr, Birmingham, AL 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 APR PY 2010 VL 130 SU 1 MA 249 BP S42 EP S42 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100248 ER PT J AU Vander Lugt, B Beck, ZT Fuhlbrigge, RC Hacohen, N Campbell, JJ Boes, M AF Vander Lugt, B. Beck, Z. T. Fuhlbrigge, R. C. Hacohen, N. Campbell, J. J. Boes, M. TI TGF-beta suppresses beta-catenin-dependent response to mechanical stimulation in dendritic cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Vander Lugt, B.; Beck, Z. T.; Fuhlbrigge, R. C.; Campbell, J. J.; Boes, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hacohen, N.] Massachusetts Gen Hosp, Charlestown, MA USA. [Hacohen, N.] MIT, Broad Inst Harvard, Cambridge, MA 02139 USA. [Boes, M.] Wilhelmina Childrens Hosp, Utrecht, Netherlands. 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 APR PY 2010 VL 130 SU 1 MA 600 BP S100 EP S100 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100599 ER PT J AU Watanabe, R Teague, I Lichtman, M Jiang, Y Kupper, TS Campbell, J Tawa, M Martin, E Adams, N Clark, R AF Watanabe, R. Teague, J. Lichtman, M. Jiang, Y. Kupper, T. S. Campbell, J. Tawa, M. Martin, E. Adams, N. Clark, R. TI The clonal malignant T cells in leukemic CTCL have diverse functionalities and cytokine production profiles SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Watanabe, R.; Teague, J.; Lichtman, M.; Jiang, Y.; Kupper, T. S.; Campbell, J.; Clark, R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Kupper, T. S.; Tawa, M.; Martin, E.; Adams, N.] Dana Farber Brigham & Womens Canc Ctr, 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 APR PY 2010 VL 130 SU 1 MA 279 BP S47 EP S47 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100278 ER PT J AU Varghese, SA Powell, TB Janech, MG Budisavljevic, MN Stanislaus, RC Almeida, JS Arthur, JM AF Varghese, Sanju A. Powell, Thomas B. Janech, Michael G. Budisavljevic, Milos N. Stanislaus, Romesh C. Almeida, Jonas S. Arthur, John M. TI Identification of Diagnostic Urinary Biomarkers for Acute Kidney Injury SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE acute kidney injury; biomarkers; diagnosis; kidney; urine ID ACUTE-RENAL-FAILURE; BETA-2-GLYCOPROTEIN-1 APOLIPOPROTEIN-H; GELATINASE-ASSOCIATED LIPOCALIN; INTENSIVE-CARE-UNIT; FRACTIONAL EXCRETION; TUBULAR MALFUNCTION; GEL-ELECTROPHORESIS; MASS-SPECTROMETRY; PROTEOMICS; MOLECULE-1 AB Acute kidney injury (AKI) is an important cause of death among hospitalized patients. The 2 most common causes of AKI are acute tubular necrosis (ATN) and prerenal azotemia (PRA). Appropriate diagnosis of the disease is important but often difficult. We analyzed urine proteins by 2-dimensional gel electrophoresis from 38 patients with AKI. Patients were randomly assigned to a training set, an internal test set, or an external validation set. Spot abundances were analyzed by artificial neural networks to identify biomarkers that differentiate between ATN and PRA. When the trained neural network algorithm was tested against the training data, it identified the diagnosis for 16 of 18 patients in the training set and all 10 patients in the internal test set. The accuracy was validated in the novel external set of patients where conditions of 9 of 10 patients were correctly diagnosed including 5 of 5 with ATN and 4 of 5 with PRA. Plasma retinol-binding protein was identified in 1 spot and a fragment of albumin and plasma retinol-binding protein in the other. These proteins are candidate markers for diagnostic assays of AKI. C1 [Varghese, Sanju A.; Powell, Thomas B.; Janech, Michael G.; Budisavljevic, Milos N.; Arthur, John M.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Budisavljevic, Milos N.; Arthur, John M.] Ralph H Johnson VA Med Ctr, Dept Med, Charleston, SC USA. [Stanislaus, Romesh C.; Almeida, Jonas S.] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. RP Arthur, JM (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,POB 250623, Charleston, SC 29425 USA. EM arthurj@musc.edu OI Janech, Michael/0000-0002-3202-4811 FU National Heart, Lung, and Blood Institute [R01DK080234]; National Institutes of Health [N01-HV-28181]; Department of Veterans Affairs FX Supported by R01DK080234 and with Federal funds as part of the NHLBI Proteomics Initiative from the National Heart, Lung, and Blood Institute, National Institutes of Health, under contract no. N01-HV-28181. Additional support for this project came from the Department of Veterans Affairs. NR 36 TC 7 Z9 7 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2010 VL 58 IS 4 BP 612 EP 620 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 583ZL UT WOS:000276719600009 PM 20224435 ER PT J AU Ning, M Sarracino, D Buonanno, F Kho, A Krastins, B Chou, S McMullin, D Lo, EH AF Ning, M. Sarracino, D. Buonanno, F. Kho, A. Krastins, B. Chou, S. McMullin, D. Lo, E. H. TI PHARMACO-PROTEOMICS AT THE BEDSIDE: A STUDY OF TPA TREATMENT IN ACUTE STROKE PATIENTS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Annual Combined Meeting of the Central-Society-for-Clinical-Research/Midwestern Section of the American-Federation-for-Medical-Research CY APR 22-23, 2010 CL Chicago, IL SP Cent Soc Clin Res, Amer Federat Med Res, Midwestern Sect C1 [Ning, M.; Sarracino, D.; Buonanno, F.; Kho, A.; Krastins, B.; Chou, S.; McMullin, D.; Lo, E. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2010 VL 58 IS 4 MA 98 BP 673 EP 673 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 583ZL UT WOS:000276719600110 ER PT J AU Burns, JA Friedman, AD Lutch, MJ Hillman, RE Zeitels, SM AF Burns, J. A. Friedman, A. D. Lutch, M. J. Hillman, R. E. Zeitels, S. M. TI Value and utility of 532 nanometre pulsed potassium-titanyl-phosphate laser in endoscopic laryngeal surgery SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Article; Proceedings Paper CT Eastern Section Meeting of the Triological-Society CY JAN 24-25, 2009 CL Boston, MA SP Triol Soc DE Larynx; Vocal Cords; Laser Surgery ID DYE-LASER; GLOTTAL PAPILLOMATOSIS; DYSPLASIA; ANESTHESIA; SINGERS AB Objectives: Recently, the 532 nm pulsed potassium-titanyl-phosphate laser has emerged as an effective angiolytic laser for treating mucosal lesions of the larynx in the operating theatre and clinic. We sought to assess the current impact of potassium-titanyl-phosphate laser on our laryngeal surgery practice. Study design: Retrospective review of 710 patients undergoing endoscopic laryngeal surgery over a one-year period. Methods: Medical records of the endoscopic laryngeal procedures were reviewed; 386/710 had been performed in the clinic and 324/710 in the operating theatre under general anaesthesia. Indications for the procedures were classified by pathology. Results: Pulsed potassium-titanyl-phosphate laser was used in 209/386 clinic procedures. The indications for these procedures were: dysplasia (114/209 procedures), papillomatosis (89/209), varices or ectasia (three of 209), and 'other' (three of 209). Pulsed potassium-titanyl-phosphate laser was used in 178/324 operating theatre endoscopic laryngeal procedures. The indications for these procedures were: cancer (54/178 procedures), dysplasia (52/178), papillomatosis (38/178), varices or ectasia (13/178), polyps (six of 178), nodules (six of 178), stenosis ( five of 178), granulation (three of 178), and amyloid (one of 178). Conclusions: Due to its versatility, the 532 nm pulsed potassium-titanyl-phosphate laser is our most commonly utilised instrument for performing endoscopic laryngeal surgery. C1 [Burns, J. A.; Friedman, A. D.; Lutch, M. J.; Hillman, R. E.; Zeitels, S. M.] Harvard Univ, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02114 USA. [Hillman, R. E.] Harvard Univ, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, Massachusetts Gen Hosp,Dept Hlth Sci & Technol, Boston, MA 02114 USA. RP Burns, JA (reprint author), Harvard Univ, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, Massachusetts Gen Hosp,Dept Surg, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM burns.james@mgh.harvard.edu NR 22 TC 4 Z9 4 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0022-2151 J9 J LARYNGOL OTOL JI J. Laryngol. Otol. PD APR PY 2010 VL 124 IS 4 BP 407 EP 411 DI 10.1017/S0022215109991824 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 586PM UT WOS:000276923300012 PM 19941682 ER PT J AU Kim, WK Sun, Y Do, H Autissier, P Halpern, EF Piatak, M Lifson, JD Burdo, TH McGrath, MS Williams, K AF Kim, Woong-Ki Sun, Yue Do, Hien Autissier, Patrick Halpern, Elkan F. Piatak, Michael, Jr. Lifson, Jeffrey D. Burdo, Tricia H. McGrath, Michael S. Williams, Kenneth TI Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE subsets; macrophage; CD16; HIV; AIDS ID PERIPHERAL-BLOOD MONOCYTES; IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; TRANSFORMING GROWTH-FACTOR; HIV-POSITIVE PATIENTS; FC-GAMMA RECEPTORS; ADHESION MOLECULES; HIV-1-INFECTED PATIENTS; MONONUCLEAR PHAGOCYTES; CD16(+) MONOCYTES AB Infection by HIV is associated with the expansion of monocytes expressing CD16 antigens, but the significance of this in HIV pathogenesis is largely unknown. In rhesus macaques, at least three subpopulations of blood monocytes were identified based on their expression of CD14 and CD16: CD14(high)CD16(-), CD14(high)CD16(low), and CD14(low)CD16(high). The phenotypes and functions of these subpopulations, including CD16(+) monocytes, were investigated in normal, uninfected rhesus macaques and macaques that were infected with SIV or chimeric SHIV. To assess whether these different monocyte subpopulations expand or contract in AIDS pathogenesis, we conducted a cross-sectional study of 54 SIV-or SHIV-infected macaques and 48 uninfected controls. The absolute numbers of monocyte populations were examined in acutely infected animals, chronically infected animals with no detectable plasma virus RNA, chronically infected animals with detectable plasma virus RNA, and animals that died with AIDS. The absolute numbers of CD14(high)CD16(low) and CD14(low)CD16(high) monocytes were elevated significantly in acutely infected animals and chronically infected animals with detectable plasma virus RNA compared with uninfected controls. Moreover, a significant, positive correlation was evident between the number of CD14(high)CD16(low) or CD14(low)CD16(high) monocytes and plasma viral load in the infected cohort. These data show the dynamic changes of blood monocytes, most notably, CD14(high)CD16(low) monocytes during lentiviral infection, which are specific to disease stage. J. Leukoc. Biol. 87: 557-567; 2010. C1 [Burdo, Tricia H.; Williams, Kenneth] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Kim, Woong-Ki; Sun, Yue; Autissier, Patrick; Williams, Kenneth] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Halpern, Elkan F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Do, Hien; McGrath, Michael S.] Pathologica LLC, San Francisco, CA USA. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [McGrath, Michael S.] Univ Calif San Francisco, Dept Lab Med, Posit Hlth Program, San Francisco, CA 94143 USA. RP Williams, K (reprint author), Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. EM williauy@bc.edu FU Public Health Service [NS040237, NS037654, NS0500041, MH81835] FX This work was supported by Public Health Service grants NS040237 (K. W.), NS037654 (K. W.), NS0500041 (K. W.), and MH81835 (K. W. and M. S. M.). NR 70 TC 42 Z9 42 U1 1 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD APR PY 2010 VL 87 IS 4 BP 557 EP 567 DI 10.1189/jlb.0209082 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 618GL UT WOS:000279339500005 PM 19843579 ER PT J AU Andronesi, OC Ramadan, S Ratai, EM Jennings, D Mountford, CE Sorensen, AG AF Andronesi, Ovidiu C. Ramadan, Saadallah Ratai, Eva-Maria Jennings, Dominique Mountford, Carolyn E. Sorensen, A. Gregory TI Spectroscopic imaging with improved gradient modulated constant adiabaticity pulses on high-field clinical scanners SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Magnetic resonance spectroscopic imaging (MRSI); Chemical shift displacement error (CSDE); Specific absorption rate (SAR); Gradient offset independent adiabatic (GOIA); Localized adiabatic selective refocusing (LASER); Brain ID SPIN-ECHO PULSE; MAGNETIC-RESONANCE; HUMAN BRAIN; RADIOFREQUENCY PULSES; REFOCUSING PULSES; MR SPECTROSCOPY; FOCI PULSES; BROAD-BAND; INVERSION; NMR AB The purpose of this work was to design and implement constant adiabaticity gradient modulated pulses that have improved slice profiles and reduced artifacts for spectroscopic imaging on 3 T clinical scanners equipped with standard hardware. The newly proposed pulses were designed using the gradient offset independent adiabaticity (GOIA. Tannus and Garwood [13]) method using WURST modulation for RF and gradient waveforms. The GOIA-WURST pulses were compared with GOIA-HSn (GOIA based on nth-order hyperbolic secant) and FOCI (frequency offset corrected inversion) pulses of the same bandwidth and duration. Numerical simulations and experimental measurements in phantoms and healthy volunteers are presented. GOIA-WURST pulses provide improved slice profile that have less slice smearing for off-resonance frequencies compared to GOIA-HSn pulses. The peak RF amplitude of GOIA-WURST is much lower (40% less) than FOCI but slightly higher (14.9% more) to GOIA-HSn. The quality of spectra as shown by the analysis of lineshapes, eddy currents artifacts, subcutaneous lipid contamination and SNR is improved for GOIA-WURST. GOIA-WURST pulse tested in this work shows that reliable spectroscopic imaging could be obtained in routine clinical setup and might facilitate the use of clinical spectroscopy. (C) 2010 Elsevier Inc. All rights reserved. C1 [Andronesi, Ovidiu C.; Ratai, Eva-Maria; Jennings, Dominique; Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Ramadan, Saadallah; Mountford, Carolyn E.] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp,Ctr Clin Spect, Boston, MA 02115 USA. RP Andronesi, OC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula Martinos Ctr Biomed Imaging, 149 14th St,Suite 2301, Boston, MA 02129 USA. EM ovidiu@nmr.mgh.harvard.edu; sorensen@nmr.mgh.harvard.edu FU NIH [R01 1200-206456] FX Funding from NIH, Grant R01 1200-206456. Discussions with Drs. Thomas Benner and Andre van der Kouwe from Martinos Center, MGH, and Drs. Nouha Salibi, Mark Brown and Josef Pfeuffer from Siemens USA are gratefully acknowledged. NR 38 TC 31 Z9 32 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD APR PY 2010 VL 203 IS 2 BP 283 EP 293 DI 10.1016/j.jmr.2010.01.010 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 578XI UT WOS:000276329700011 PM 20163975 ER PT J AU Wu, YT Hrovat, MI Ackerman, JL Reese, TG Cao, HH Ecklund, K Glimcher, MJ AF Wu, Yaotang Hrovat, Mirko I. Ackerman, Jerome L. Reese, Timothy G. Cao, Haihui Ecklund, Kirsten Glimcher, Melvin J. TI Bone Matrix Imaged In Vivo by Water- and Fat-Suppressed Proton Projection MRI (WASPI) of Animal and Human Subjects SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE bone; MRI; WASPI; UTE ultrashort T2 imaging; osteoporosis; osteomalacia ID QUANTITATIVE COMPUTED-TOMOGRAPHY; DENSITY; OSTEOPOROSIS; NMR; OSTEOMALACIA; PHOSPHORUS; MANAGEMENT; SEQUENCES; GEOMETRY AB Purpose: To demonstrate water- and fat-suppressed proton projection MRI (WASPI) in a clinical scanner to visualize the solid bone matrix in animal and human subjects. Materials and Methods: Pig bone specimens and polymer pellets were used to optimize the WASPI method in terms of soft-tissue suppression, image resolution, signal-to-noise ratio, and scan time on a 3T MRI scanner The ankles of healthy 2-3-month-old live Yorkshire pigs were scanned with the optimized method. The method was also applied to the wrists of six healthy adult human volunteers to demonstrate the feasibility of the WASPI method in human subjects. A transmit/receive coil built with proton-free materials was utilized to produce a strong B(1) field. A fast transmit/receive switch was developed to reduce the long receiver dead time that would otherwise obscure the signals. Results: Clear 3D WASPI images of pig ankles and human wrists, showing only the solid bone matrix and other tissues with high solid content (eg, tendons), with a spatial resolution of 2.0 mm in all three dimensions were obtained in as briefly as 12 minutes. Conclusion: WASPI of the solid matrix of bone in humans and animals in vivo is feasible. C1 [Wu, Yaotang; Ackerman, Jerome L.; Cao, Haihui; Glimcher, Melvin J.] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Wu, Yaotang; Ackerman, Jerome L.; Reese, Timothy G.; Cao, Haihui] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Wu, Yaotang; Ackerman, Jerome L.; Reese, Timothy G.; Cao, Haihui; Ecklund, Kirsten; Glimcher, Melvin J.] Harvard Univ, Sch Med, Boston, MA USA. [Hrovat, Mirko I.] Mirtech, Brockton, MA USA. [Ecklund, Kirsten] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Wu, YT (reprint author), Childrens Hosp, Dept Orthopaed Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM yaotang.wu@childrens.harvard.edu RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 FU NIBIB-NIH; NIA-NIH FX Contract grant sponsor: NIBIB-NIH; NIA-NIH. NR 40 TC 20 Z9 20 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD APR PY 2010 VL 31 IS 4 BP 954 EP 963 DI 10.1002/jmri.22130 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 578WU UT WOS:000276328200022 PM 20373441 ER PT J AU Lecumberri, B Fernandez-Rebollo, E Sentchordi, L Saavedra, P Bernal-Chico, A Pallardo, LF Bustos, JMJ Castano, L de Santiago, M Hiort, O de Nanclares, GP Bastepe, M AF Lecumberri, B. Fernandez-Rebollo, E. Sentchordi, L. Saavedra, P. Bernal-Chico, A. Pallardo, L. F. Jimenez Bustos, J. M. Castano, L. de Santiago, M. Hiort, O. Perez de Nanclares, G. Bastepe, M. TI Coexistence of two different pseudohypoparathyroidism subtypes (Ia and Ib) in the same kindred with independent Gs alpha coding mutations and GNAS imprinting defects SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID ALBRIGHTS HEREDITARY OSTEODYSTROPHY; CONTROL ELEMENT; METHYLATION; G(S)ALPHA; FEATURES; DELETION; LOCUS AB Background Pseudohypoparathyroidism (PHP) defines a rare group of disorders whose common feature is resistance to the parathyroid hormone. Patients with PHP-Ia display additional hormone resistance, Albright hereditary osteodystrophy (AHO) and reduced Gs alpha activity in easily accessible cells. This form of PHP is associated with heterozygous inactivating mutations in Gs alpha-coding exons of GNAS, an imprinted gene locus on chromosome 20q13.3. Patients with PHP-Ib typically have isolated parathyroid hormone resistance, lack AHO features and demonstrate normal erythrocyte Gs alpha activity. Instead of coding Gs alpha mutations, patients with PHP-Ib display imprinting defects of GNAS, caused, at least in some cases, by genetic mutations within or nearby this gene. Patients Two unrelated PHP families, each of which includes at least one patient with a Gs alpha coding mutation and another with GNAS loss of imprinting, are reported here. Results One of the patients with GNAS imprinting defects has paternal uniparental isodisomy of chromosome 20q, explaining the observed imprinting abnormalities. The identified Gs alpha coding mutations include a tetranucleotide deletion in exon 7, which is frequently found in PHP-Ia, and a novel single nucleotide change at the acceptor splice junction of intron 11. Conclusions These molecular data reveal an interesting mixture, in the same family, of both genetic and epigenetic mutations of the same gene. C1 [Lecumberri, B.; Pallardo, L. F.; de Santiago, M.] Hosp Univ La Paz, Serv Endocrinol, Madrid, Spain. [Fernandez-Rebollo, E.; Bernal-Chico, A.; Castano, L.; Perez de Nanclares, G.] Hosp Cruces, Mol Genet Lab, Endocrinol & Diabet Res Grp, Baracaldo, Bizkaia, Spain. [Fernandez-Rebollo, E.; Bastepe, M.] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Fernandez-Rebollo, E.; Bastepe, M.] Harvard Univ, Sch Med, Boston, MA USA. [Sentchordi, L.; Jimenez Bustos, J. M.] Hosp Univ Guadalajara, Serv Pediat, Castilla La Mancha, Spain. [Sentchordi, L.] Hosp Infanta Leonor, Serv Pediat, Madrid, Spain. [Saavedra, P.] Hosp Principe Asturias, Serv Endocrinol, Madrid, Spain. [Castano, L.; Perez de Nanclares, G.] Ctr Invest Biomed Red Enfermedades Raras, Baracaldo, Bizkaia, Spain. [Castano, L.] Univ Basque Country, Sch Med, Bilbao, Spain. [Hiort, O.] Univ Lubeck, Dept Pediat & Adolescent Med, Lubeck, Germany. RP de Nanclares, GP (reprint author), Hosp Txagorritxu, Mol Genet Lab, Res Unit, E-01009 Alava, Basque Country, Spain. EM gnanclares@osakidetza.net; bastepe@helix.mgh.harvard.edu OI FERNANDEZ-REBOLLO, EDUARDO/0000-0002-4378-7590; Castano, Luis/0000-0003-0437-9401 FU Instituto de Salud Carlos III of the Spanish Ministry of Health [CP03/0064]; Department of Health of the Basque Government [GV2008/111035]; Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK073911]; German Ministry of Research and Education [GMG01GM0315]; National Institutes of Health; [BIO08/ER/001] FX GPN is supported by Miguel Servet contracts from the Instituto de Salud Carlos III of the Spanish Ministry of Health (grant CP03/0064). This work was partially funded by grant GV2008/111035 from the Department of Health of the Basque Government and BIO08/ER/001. This group is also supported by the Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII. This work was also funded, in part, by grant number R01DK073911 from the National Institute of Diabetes and Digestive and Kidney Diseases (to MB) and from the German Ministry of Research and Education (GMG01GM0315 to OH). Other Funders: National Institutes of Health. NR 14 TC 28 Z9 28 U1 2 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD APR PY 2010 VL 47 IS 4 BP 276 EP 280 DI 10.1136/jmg.2009.071001 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 587AF UT WOS:000276957600011 PM 19858129 ER PT J AU Alexander, LEC Maisey, HC Timmer, AM Rooijakkers, SHM Gallo, RL von Kockritz-Blickwede, M Nizet, V AF Alexander, Laura E. Crotty Maisey, Heather C. Timmer, Anjuli M. Rooijakkers, Suzan H. M. Gallo, Richard L. von Koeckritz-Blickwede, Maren Nizet, Victor TI M1T1 group A streptococcal pili promote epithelial colonization but diminish systemic virulence through neutrophil extracellular entrapment SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE Group A Streptococcus; Pilus; Virulence factor; IL-8; Neutrophil extracellular traps ID SERUM OPACITY FACTOR; PYOGENES DISEASE; CELL-ADHESION; T-ANTIGENS; PATHOGENESIS; RESISTANCE; INFECTION; PROTEIN; TRAPS; IL-8 AB Group A Streptococcus is a leading human pathogen associated with a diverse array of mucosal and systemic infections. Cell wall anchored pili were recently described in several species of pathogenic streptococci, and in the case of GAS, these surface appendages were demonstrated to facilitate epithelial cell adherence. Here we use targeted mutagenesis to evaluate the contribution of pilus expression to virulence of the globally disseminated M1T1 GAS clone, the leading agent of both GAS pharyngitis and severe invasive infections. We confirm that pilus expression promotes GAS adherence to pharyngeal cells, keratinocytes, and skin. However, in contrast to findings reported for group B streptococcal and pneumococcal pili, we observe that pilus expression reduces GAS virulence in murine models of necrotizing fasciitis, pneumonia and sepsis, while decreasing GAS survival in human blood. Further analysis indicated the systemic virulence attenuation associated with pilus expression was not related to differences in phagocytic uptake, complement deposition or cathelicidin antimicrobial peptide sensitivity. Rather, GAS pili were found to induce neutrophil IL-8 production, promote neutrophil transcytosis of endothelial cells, and increase neutrophil release of DNA-based extracellular traps, ultimately promoting GAS entrapment and killing within these structures. C1 [Alexander, Laura E. Crotty; Maisey, Heather C.; Timmer, Anjuli M.; Rooijakkers, Suzan H. M.; von Koeckritz-Blickwede, Maren; Nizet, Victor] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. [Alexander, Laura E. Crotty] Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02114 USA. [Rooijakkers, Suzan H. M.] Univ Med Ctr Utrecht, NL-3584 CX Utrecht, Netherlands. [Gallo, Richard L.] Univ Calif San Diego, Div Dermatol, La Jolla, CA 92093 USA. [Gallo, Richard L.] VA San Diego Hlth Care Syst, San Diego, CA USA. [Nizet, Victor] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Nizet, Victor] Rady Childrens Hosp, San Diego, CA 92123 USA. RP Nizet, V (reprint author), Univ Calif San Diego, Dept Pediat, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM vnizet@ucsd.edu OI Gallo, Richard/0000-0002-1401-7861; Crotty Alexander, Laura/0000-0002-5091-2660 FU Hartwell Foundation [AI077780]; European Molecular Biology Organization; National Science Foundation (NSF); Deutsche Akademie der Naturforscher Leopoldina [BMBF-LPD 9901/8-187] FX This work was supported by NIH grant AI077780 to V. N. L. E. C. A. received a fellowship from The Hartwell Foundation. S. H. M. R. was supported by a grant from the European Molecular Biology Organization, H. C. M. by a National Science Foundation (NSF) Graduate Research Fellowship, A. M. T. by an A. P. Giannini Foundation Postdoctoral Fellowship and M. v. K.-B. through a fellowship from the Deutsche Akademie der Naturforscher Leopoldina (BMBF-LPD 9901/8-187). We thank Anna Cogen for sharing protocols for bacterial adherence to mouse skin. NR 48 TC 21 Z9 21 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD APR PY 2010 VL 88 IS 4 BP 371 EP 381 DI 10.1007/s00109-009-0566-9 PG 11 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 573IG UT WOS:000275905300007 ER PT J AU Holdhoff, M Supko, JG Gallia, GL Hann, CL Bonekamp, D Ye, XB Cao, B Olivi, A Grossman, SA AF Holdhoff, Matthias Supko, Jeffrey G. Gallia, Gary L. Hann, Christine L. Bonekamp, David Ye, Xiaobu Cao, Bing Olivi, Alessandro Grossman, Stuart A. TI Intratumoral concentrations of imatinib after oral administration in patients with glioblastoma multiforme SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Imatinib mesylate; Intratumoral concentration; Glioblastoma multiforme; Malignant glioma ID BRAIN-TUMOR CONSORTIUM; MALIGNANT GLIOMAS; PHASE-II; MESYLATE; HYDROXYUREA; PHARMACOKINETICS; TRANSPORT; STI-571; BARRIER; PLASMA AB Imatinib, an orally administered tyrosine kinase inhibitor of PDGF receptor, c-abl and c-kit, is currently in clinical trials to assess its efficacy in malignant gliomas. Although imatinib does not readily penetrate an intact blood-brain barrier (BBB), the extent to which it distributes into regions of high grade gliomas where the BBB is compromised has not been determined. Patients with recurrent high-grade gliomas for whom repeat surgical tumor debulking was clinically indicated received imatinib mesylate 600 mg orally once a day for seven days prior to surgery. Tissue samples were collected from different regions of the tumor and the approximate location of these samples was determined using frameless stereotactic neuronavigation. Plasma samples were obtained immediately before and after the resection. The concentration of imatinib in the plasma and tumor samples was determined using high performance liquid chromatography with mass spectrometric detection. Eleven tumor samples were obtained from three patients with recurrent glioblastoma multiforme. The median concentration of imatinib in these 11 tumor specimens was 1.34 mu g/g (range 0.21-4.31 mu g/g) and the median tumor-to-plasma ratio was 0.71 (range 0.28-3.03). These findings suggest that imatinib can reach intratumoral concentrations similar to those or higher than in plasma in regions of glioblastoma where the BBB is disrupted as indicated by contrast enhancement on magnetic resonance imaging. C1 [Holdhoff, Matthias; Gallia, Gary L.; Hann, Christine L.; Ye, Xiaobu; Cao, Bing; Olivi, Alessandro; Grossman, Stuart A.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Brain Canc Program, Baltimore, MD 21231 USA. [Supko, Jeffrey G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Gallia, Gary L.; Olivi, Alessandro] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21231 USA. [Bonekamp, David] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21231 USA. RP Holdhoff, M (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Brain Canc Program, Canc Res Bldg 2,Suite 1 M-16 1550 Orleans St, Baltimore, MD 21231 USA. EM mholdho1@jhmi.edu RI Olivi, Alessandro/K-6531-2016 OI Olivi, Alessandro/0000-0002-4489-7564 FU NCI NIH HHS [P30 CA006973] NR 17 TC 24 Z9 25 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD APR PY 2010 VL 97 IS 2 BP 241 EP 245 DI 10.1007/s11060-009-0008-0 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 568VV UT WOS:000275553200009 PM 19768386 ER PT J AU Hewett, J Johanson, P Sharma, N Standaert, D Balcioglu, A AF Hewett, Jeff Johanson, Peter Sharma, Nutan Standaert, David Balcioglu, Aygul TI Function of dopamine transporter is compromised in DYT1 transgenic animal model in vivo SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dopamine; DYT1 dystonia; locomotion; mouse; no-net flux microdialysis; striatum ID ONSET TORSION DYSTONIA; MOUSE MODEL; MUTANT TORSINA; ENDOPLASMIC-RETICULUM; NUCLEUS-ACCUMBENS; MICE LACKING; AMPHETAMINE; PROTEIN; COCAINE; GENE AB P>Early onset torsion dystonia (DYT1), the most common form of hereditary primary dystonia, is caused by a mutation in the TOR1A gene, which codes for the protein, torsinA. We previously examined the effect of the human mutant torsinA on striatal dopaminergic function in a conventional transgenic mouse model of DYT1 dystonia (hMT1), in which human mutant torsinA is expressed under the cytomegalovirus promotor. Systemic administration of amphetamine did not increase dopamine (DA) release as efficiently in these mice as compared with wild-type transgenic and non-transgenic mice. We, now, studied the contribution of the DA transporter (DAT) to amphetamine-induced DA release in hMT1 transgenic mice using in vivo no-net flux microdialysis. This method applies different concentrations of DA through the microdialysis probe and measures DA concentration at the output of the probe following an equilibrium period. The slope (extraction fraction) is the measure of the DAT activity in vivo. The slope for hMT1 transgenic mice was 0.58 +/- 0.07 and for non-transgenic animals, 0.87 +/- 0.06 (p < 0.05). We further investigated the efficacy of nomifensine (a specific DAT inhibitor) in inhibiting amphetamine-induced DA release. Local application of nomifensine 80 min before the systemic application of amphetamine inhibited DA release in both transgenic mice and their non-transgenic littermates. The efficiency of the inhibition appeared to be different, with mean values of 48% for hMT1 transgenic mice versus 84% for non-transgenic littermates. Moreover, we have evaluated basal and amphetamine-induced locomotion in hMT1 transgenic mice compared with their non-transgenic littermates, using an O-maze behavioral chamber. Basal levels of locomotion in the hMT1 transgenic mice showed that they moved much less than their non-transgenic littermates (0.9 +/- 0.3 m for transgenic mice vs. 2.4 +/- 0.7 m for non-transgenic littermates, p < 0.05). This relative reduction in locomotion was also observed following amphetamine administration (48.5 +/- 6.7 m for transgenics vs. 73.7 +/- 9.8 m for non-transgenics, p < 0.05). These results support the finding that there are altered dynamics of DA release and reuptake in hMT1 transgenic mice in vivo, with DAT activity is reduced in the presence of mutant torsinA, which is consistent with behavioral consequences such as reduced locomotion and (previously described) abnormal motor phenotypes such as increased hind-base width and impaired performance on the raised-beam task. These data implies that altered DAT function may contribute to impaired DA neurotransmission and clinical symptoms in human DYT1 dystonia. C1 [Hewett, Jeff; Johanson, Peter; Sharma, Nutan; Balcioglu, Aygul] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Standaert, David] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. RP Balcioglu, A (reprint author), Massachusetts Gen Hosp, Dept Neurol, 149 13th St,Room 6217, Charlestown, MA 02129 USA. EM abalcioglu@partners.org OI Standaert, David/0000-0003-2921-8348 FU Dystonia Medical Research Foundation (DMRF); Parkinson's and Movement Disorders Foundation (PMDF) FX We thank Dr Xandra Breakefield for helpful advice. This work was supported by Dystonia Medical Research Foundation (DMRF) and Parkinson's and Movement Disorders Foundation (PMDF) grants to Dr Aygul Balcioglu. NR 53 TC 25 Z9 25 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2010 VL 113 IS 1 BP 228 EP 235 DI 10.1111/j.1471-4159.2010.06590.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 564AS UT WOS:000275183500019 PM 20132487 ER PT J AU Nam, EC Handzel, O Levine, RA AF Nam, Eui-Cheol Handzel, Ophir Levine, Robert A. TI Carbamazepine responsive typewriter tinnitus from basilar invagination SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID TRIGEMINAL NEURALGIA AB Basilar invagination due to a congenital skeletal disorder kinked the brainstem at the ponto-medullary junction causing both auditory nerves to make an acute turn at the porus acousticus. The associated bilateral asynchronous clicking tinnitus responded to carbamazepine. C1 [Levine, Robert A.] Harvard Univ, Dept Otolaryngol, Massachusetts Gen Hosp,Eaton Peabody Lab, Massachusetts Eye & Ear Infirm,Med Sch, Boston, MA 02114 USA. [Levine, Robert A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Nam, Eui-Cheol] Kangwon Natl Univ, Coll Med, Dept Otolaryngol, Chunchon, South Korea. [Handzel, Ophir] Tel Aviv Univ, Dept Otolaryngol Head & Neck Surg, Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. RP Levine, RA (reprint author), Harvard Univ, Dept Otolaryngol, Massachusetts Gen Hosp,Eaton Peabody Lab, Massachusetts Eye & Ear Infirm,Med Sch, 243 Charles St, Boston, MA 02114 USA. EM robert_levine@meei.harvard.edu RI Handzel, Ophir/D-8236-2017 OI Handzel, Ophir/0000-0002-6905-3034 FU Tinnitus Research Initiative; American Tinnitus Association FX The authors gratefully acknowledge the support of the Tinnitus Research Initiative, J and S Blais, K and A Griffin, Kangwon National University Overseas Faculty Research Programme 2005 (E-C Nam) and the American Tinnitus Association. NR 10 TC 6 Z9 6 U1 1 U2 7 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD APR PY 2010 VL 81 IS 4 BP 456 EP 458 DI 10.1136/jnnp.2009.173104 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 576RD UT WOS:000276163600023 PM 20360168 ER PT J AU Vijayan, S Hale, GJ Moore, CI Brown, EN Wilson, M AF Vijayan, Sujith Hale, Greg J. Moore, Christopher I. Brown, Emery N. Wilson, Matthew TI Activity in the Barrel Cortex During Active Behavior and Sleep SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PRIMARY SOMATOSENSORY CORTEX; RECEPTIVE-FIELDS; TEXTURE-DISCRIMINATION; AUDITORY-CORTEX; SENSORY RESPONSES; VIBRISSA CORTEX; PYRAMIDAL CELLS; NEURAL ENSEMBLE; SPINY STELLATE; AWAKE RAT AB Vijayan S, Hale GJ, Moore CI, Brown EN, Wilson M. Activity in the barrel cortex during active behavior and sleep. J Neurophysiol 103: 2074-2084, 2010. First published February 17, 2010; doi: 10.1152/jn.00474.2009. The rate at which neurons fire has wide-reaching implications for the coding schemes used by neural systems. Despite the extensive use of the barrel cortex as a model system, relatively few studies have examined the rate of sensory activity in single neurons in freely moving animals. We examined the activity of barrel cortex neurons in behaving animals during sensory cue interaction, during non-stimulus-related activity, during various states of sleep, and during the administration of isoflurane. The activity of regular-spiking units (RSUs: predominantly excitatory neurons) and fast spiking units (FSUs: a subtype of inhibitory interneurons) was examined separately. We characterized activity by calculating neural firing rates, because several reports have emphasized the low firing rates in this system, reporting that both baseline activity and stimulus evoked activity is <1 Hz. We report that, during sensory cue interaction or non-stimulus-related activity, the majority of RSUs in rat barrel cortex fired at rates significantly >1 Hz, with 27.4% showing rates above 10 Hz during cue interaction. Even during slow wave sleep, which had the lowest mean and median firing rates of any nonanesthetized state observed, 80.0% of RSUs fired above 1 Hz. During all of the nonanesthetized states observed 100% of the FSUs fired well above 1 Hz. When rats were administered isoflurane and at a depth of anesthesia used in standard in vivo electrophysiological preparations, all of the RSUs fired below 1 Hz. We also found that >80% of RSUs either upmodulated or downmodulated their firing during cue interaction. These data suggest that low firing rates do not typify the output of the barrel cortex during awake activity and during sleep and indicate that sensory coding at both the individual and population levels may be nonsparse. C1 [Hale, Greg J.; Wilson, Matthew] MIT, RIKEN, MIT Neurosci Res Ctr, Cambridge, MA 02139 USA. [Vijayan, Sujith] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Vijayan, Sujith; Hale, Greg J.; Wilson, Matthew] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Hale, Greg J.; Moore, Christopher I.; Brown, Emery N.; Wilson, Matthew] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Moore, Christopher I.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Brown, Emery N.] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Wilson, M (reprint author), MIT, RIKEN, MIT Neurosci Res Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mwilson@mit.edu FU RIKEN; National Institutes of Health [R01 DA-015644, DP1-OD003646, T32 HL-07901-05 to -07] FX This work was supported by a RIKEN grant to M. Wilson and National Institutes of Health Grants R01 DA-015644 to M. Wilson, and E. N. Brown and DP1-OD003646 to E. N. Brown, and T32 HL-07901-05 to -07 to S. Vijayan. NR 71 TC 16 Z9 16 U1 2 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2010 VL 103 IS 4 BP 2074 EP 2084 DI 10.1152/jn.00474.2009 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 581WI UT WOS:000276555800035 PM 20164403 ER PT J AU Lucas, MR AF Lucas, Michele R. TI Psychosocial Implications for the Patient With a High-Grade Glioma SO JOURNAL OF NEUROSCIENCE NURSING LA English DT Article ID QUALITY-OF-LIFE; MALIGNANT BRAIN-TUMORS; CANCER-PATIENTS; CHEMOTHERAPY; RADIOTHERAPY; PERCEPTIONS; DYSFUNCTION; RADIATION; SURVIVORS; DISTRESS AB The purpose of this article was to explore the psychosocial implications of being diagnosed with a high-grade glioma, World Health Organization III/IV and IV/IV, to better inform healthcare providers and researchers of the patient experience. The information is the cumulative data collected from hundreds of patient interviews in a large metropolitan brain tumor clinic over a 7-year period. Three themes of loss emerged-loss of independence, loss of self, and loss of relationships. This information is presented on behalf of the patients for acknowledgement of their experience and for identification of the need for increased psychological and concrete services to better serve this population. C1 Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. RP Lucas, MR (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. EM mrlucas@partners.org NR 40 TC 12 Z9 12 U1 2 U2 2 PU AMER ASSOC NEUROSCIENCE NURSES PI GLENVIEW PA 4700 W LAKE AVENUE, GLENVIEW, IL 60025 USA SN 0888-0395 J9 J NEUROSCI NURS JI J. Neurosci. Nurs. PD APR PY 2010 VL 42 IS 2 BP 104 EP 108 PG 5 WC Clinical Neurology; Nursing SC Neurosciences & Neurology; Nursing GA 576CU UT WOS:000276122400007 PM 20422796 ER PT J AU Wilkinson, HA AF Wilkinson, Harold A. TI Meralgia paresthetica SO JOURNAL OF NEUROSURGERY 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 0 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 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD APR PY 2010 VL 112 IS 4 BP 902 EP 902 DI 10.3171/2009.6.JNS09790 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 574ZQ UT WOS:000276033200039 PM 20367387 ER PT J AU Gerszten, PC Smuck, M Rathmell, JP Simopoulos, TT Bhagia, SM Mocek, CK Crabtree, T Bloch, DA AF Gerszten, Peter C. Smuck, Matthew Rathmell, James P. Simopoulos, Thomas T. Bhagia, Sarjoo M. Mocek, Christopher K. Crabtree, Tami Bloch, Daniel A. CA SPINE Study Grp TI Plasma disc decompression compared with fluoroscopy-guided transforaminal epidural steroid injections for symptomatic contained lumbar disc herniation: a prospective, randomized, controlled trial Clinical article SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE contained disc herniation; disc decompression; epidural steroid injection; lumbosacral spine; low-back pain; minimally invasive spine surgery; plasma disc decompression ID LOW-BACK-PAIN; NATURAL-HISTORY; FOLLOW-UP; NONOPERATIVE TREATMENT; SPINE SURGERY; LUMBOSACRAL RADICULOPATHY; IMPORTANT DIFFERENCE; COMMUNITY HOSPITALS; SALINE SOLUTIONS; OUTCOME SCORES AB Object. Patients with radiculopathy, with or without back pain, often do not respond to conservative care and may be considered for epidural steroid injection therapy or a disc decompression procedure. Plasma disc decompression (PDD) using the Coblation SpineWand device is a percutaneous, minimally invasive interventional procedure. The purpose of this study was to evaluate clinical outcomes with PDD as compared with standard care using fluoroscopy-guided transforaminal epidural steroid injection (TFESI) over the course of 2 years. Methods. This was a multicenter randomized controlled clinical study. Ninety patients (18-66 years old) who had sciatica (visual analog scale score >= 50) associated with a single-level lumbar contained disc herniation were enrolled. In all cases, their condition was refractory to initial conservative care and 1 epidural steroid injection had failed. Participants were randomly assigned to receive either PDD (46 patients) or TFESI (44 patients, up to 2 injections). Results. The patients in the PDD Group had significantly greater reduction in leg pain scores and significantly improved Oswestry Disability Index and 36-Item Short Form Health Survey ([SF-36], physical function, bodily pain, social function, and physical components summary) scores than those in the TFESI Group. During the 2-year follow-up, 25 (56%) of the patients in the PDD Group and 11 (28%) of those in the TFESI Group remained free from having a secondary procedure following the study procedure (log-rank p = 0.02). A significantly higher percentage of patients in the PDD Group showed minimum clinically important change in scores for leg and back pain and SF36 scores that exceeded literature-based minimum clinically important changes. Procedure-related adverse events. including injection site pain, increased leg or back pain, weakness, and lightheadedness, were observed in 5 patients in the PDD Group (7 events) and 7 in the TFES1 Group (14 events). Conclusions. In study patients who had radicular pain associated with a contained lumbar disc herniation, those patients treated with PDD had significantly reduced pain and better quality of life scores than those treated using repeated TFESI. In addition, significantly more PDD patients than TFESI patients avoided having to undergo a secondary procedure during the 2-year study follow-up. (DOI: 10.3171/2009.10.SPINE09208) C1 [Gerszten, Peter C.] Univ Pittsburgh, Dept Neurol Surg, Med Ctr, Pittsburgh, PA 15213 USA. [Smuck, Matthew] Stanford Univ, Stanford Intervent Spine Ctr, Redwood City, CA USA. [Bloch, Daniel A.] Stanford Univ, Div Biostat, Stanford, CA 94305 USA. [Rathmell, James P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rathmell, James P.; Simopoulos, Thomas T.] Harvard Univ, Sch Med, Boston, MA USA. [Simopoulos, Thomas T.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bhagia, Sarjoo M.] OrthoCarolina, Charlotte, NC USA. [Mocek, Christopher K.] Innovat Spine Care, Little Rock, AR USA. RP Gerszten, PC (reprint author), Univ Pittsburgh, Dept Neurol Surg, Med Ctr, Suite B-400,200 Lothrop St, Pittsburgh, PA 15213 USA. EM gersztenpc@upmc.edu FU ArthroCare Corp FX Financial support for the conduct of this study was provided by the ArthroCare Corp. In addition, the following authors report being consultants for ArthroCare Corp: Ms. Crabtree, Dr. Bloch, Dr. Gerszten, and Dr. Smock; Dr. Smuck reports financial support from ArthroCare Corp. for non study-related clinical or research effort overseen by him. NR 86 TC 35 Z9 37 U1 4 U2 11 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 APR PY 2010 VL 12 IS 4 BP 357 EP 371 DI 10.3171/2009.10.SPINE09208 PG 15 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 574AD UT WOS:000275959900005 PM 20201654 ER PT J AU Firth, PG Szabo, MD AF Firth, Paul G. Szabo, Michele D. TI Autologous Transfusion of a Neurosurgical Patient With Sickle Cell Disease SO JOURNAL OF NEUROSURGICAL ANESTHESIOLOGY LA English DT Letter ID ANESTHESIA C1 [Firth, Paul G.; Szabo, Michele D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. RP Firth, PG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. 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 0898-4921 J9 J NEUROSURG ANESTH JI J. Neurosurg. Anesthesiol. PD APR PY 2010 VL 22 IS 2 BP 180 EP 180 PG 1 WC Anesthesiology; Clinical Neurology; Surgery SC Anesthesiology; Neurosciences & Neurology; Surgery GA 579NZ UT WOS:000276379700013 PM 20118797 ER PT J AU Sun, B Abadjian, L Rempel, H Calosing, C Rothlind, J Pulliam, L AF Sun, Bing Abadjian, Linda Rempel, Hans Calosing, Cyrus Rothlind, Johannes Pulliam, Lynn TI Peripheral biomarkers do not correlate with cognitive impairment in highly active antiretroviral therapy-treated subjects with human immunodeficiency virus type 1 infection SO JOURNAL OF NEUROVIROLOGY LA English DT Article ID CEREBRAL VOLUME LOSS; HIV-INFECTION; NEUROCOGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E; AIDS DEMENTIA; VIRAL LOAD; ACTIVATION; PERFORMANCE; DYSFUNCTION; DISORDERS AB Neuropsychological (NP) impairments in human immunodeficiency virus (HIV)-infected individuals remain high despite the introduction of highly active antiretroviral therapy (HAART). We sought to determine whether or not a monocyte gene expression profile along with other peripheral factors would correlate with neuropsychological impairment among HIV-infected individuals. Forty-four HIV-1-seropositive subjects (HIV+) on HAART and 11 HIV-1-seronegative controls (HIV-) had NP testing and blood drawn for monocyte gene expression analysis. All HIV+ subjects were assessed for CD4 counts, apolipoprotein E (ApoE) genotype, viral load, and plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14). NP scores were normalized to age, gender, and education. Twenty-five percent of HIV+ individuals showed abnormal NP testing results (> 1.5 SD below normal in two domains). HIV+ individuals had deficits in attention/working memory, verbal learning, and information processing speed compared to HIV- controls. There was no correlation between overall NP impairment and plasma viral load, level of education, age, ethnic diversity, sCD14, plasma LPS, CD4 cell count, ApoE genotype, or years of infection. However, greater years of infection had worse visual learning performance. sCD14 and CD4 nadir positively correlated with information processing speed and fine motor skills, respectively. LPS correlated with viral load but not cognitive impairment. Monocyte gene expression confirmed a chronic inflammatory profile that correlated with viral load but not cognition. No blood index or profile was associated with overall NP impairment.1 year) paraplegia (T1-T10) or tetraplegia (C4-C8). Methods: Blood samples were collected before and after the first and eighth sessions (2 sessions per week for 4 weeks) of FES exercise. Results: Platelet aggregation was inhibited by 20% after the first session and by 40% (P < 0.001) after the eighth session. Thrombin activity was unchanged after the first session (10.7 +/- 0.85 s to 10.43 +/- 0.56 s) and decreased after the eighth session (12.5 +/- 1.98 s to 11.1 +/- 1.7 s; P < 0.0003). Antithrombin III activity increased after the first (103.8% +/- 8.9% to 110% +/- 6.9%; P < 0.0008) and eighth sessions (107.8% +/- 12.1% to 120.4% +/- 13.1%; P < 0.0001). Cyclic adenosine monophosphate increased after the first (9.9% +/- 2.5% to 15.8% +/- 3%; P < 0.001) and eighth sessions (17.8% +/- 4.2% to 36.5% +/- 7.6%; P < 0.0001). After the eighth session, factors V and X increased significantly (88% +/- 27% to 103% +/- 23%, P < 0.0001; 100% +/- 40% to 105% +/- 7%, P < 0.01, respectively); factors VII and VIII and fibrinogen did not change significantly. A significant reduction in platelet activation/aggregation was demonstrated in response to FES-LCE. The decrease in thrombin level was caused by the simultaneous increase in antithrombin activity. Conclusion: These findings provide new insight into the potential protective effects of FES-LCE against the risk of cardiovascular disease. C1 [Kahn, Nighat N.] James J Peters VA Med Ctr, RR&D Ctr Excellence, Bronx, NY 10468 USA. [Kahn, Nighat N.; Feldman, Susan P.; Bauman, William A.] Mt Sinai Sch Med, New York, NY USA. RP Kahn, NN (reprint author), James J Peters VA Med Ctr, RR&D Ctr Excellence, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM nighat.kahn@va.gov NR 51 TC 3 Z9 3 U1 1 U2 2 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD APR PY 2010 VL 33 IS 2 BP 150 EP 158 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 595BG UT WOS:000277585100008 PM 20486534 ER PT J AU Raffetto, JD Barros, YVR Wells, AK Khalil, RA AF Raffetto, Joseph D. Barros, Yaskara V. R. Wells, Amanda K. Khalil, Raouf A. TI MMP-2 Induced Vein Relaxation via Inhibition of [Ca(2+)](e)-Dependent Mechanisms of Venous Smooth Muscle Contraction. Role of RGD Peptides SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE vascular smooth muscle; calcium; inferior vena cave; extracellular matrix; matrix metalloproteinase; varicose veins ID MATRIX METALLOPROTEINASES; VARICOSE-VEINS; ARTERIOLAR VASODILATION; K+ CHANNELS; INTEGRIN; ACTIVATION; HYPERTENSION; RESISTANCE; ALPHA(V)BETA(3); CONSTRICTION AB Background. Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of varicose veins. We have shown that MMP-2 causes relaxation of venous segments and suggested a role of venous smooth muscle (VSM) hyperpolarization; however, the downstream mechanisms are unclear. We tested whether MMP-2 induced venous relaxation involves inhibition of the Ca(2+) mobilization mechanisms of VSM contraction due to generation of Arg-Gly-Asp (RGD)-containing peptides. Methods. Circular segments of inferior vena cava (IVC) were isolated from male Sprague-Dawley rats, suspended between two wires in a tissue bath, and isometric contraction was measured. Contraction data in mg/mg tissue were presented as means +/- SEM. Results. In IVC incubated in normal Krebs (2.5 mM Ca(2+)), the a-adrenergic agonist phenylephrine (Phe, 10(-5) M) caused initial peak (133.2 +/- 17.5) followed by a maintained contraction (73.4 +/- 11.6), that was inhibited by MMP-2 (1 mu g/mL) to 32.4 +/- 12.8 in 30 min. The inhibitory effects of MMP-2 were reversible by washing the tissue with Krebs or in the presence of the MMP inhibitors TIMP-1 (1 mu g/mL), Ro 28-2653, and BB-94 (10(-6) M), and were not associated with changes in IVC structure, demonstrating specificity. Angiotensin II (AngII, 10(-6) M) caused a monophasic contraction (114.2 +/- 12.2), that was also inhibited by MMP-2 (66.0 +/- 7.4), suggesting a post-receptor effect on the downstream mechanisms of VSM contraction. To test the role of Ca(2+) release from the sarcoplasmic reticulum, IVC was incubated in Ca(2+)-free 2 mM ethylene glycol-bis(2-aminoethyl ether-N,N,N',N'-tetra-acetic acid (EGTA) Krebs with or without MMP-2. In Ca2+-free Krebs, caffeine did not cause contraction, suggesting a limited role of the Ca(2+)-induced Ca(2+)-release mechanism, and Phe and AngII caused a small contraction (7.2 +/- 1.7 and 14.9 +/- 2.8) that was slightly increased by MMP-2 (10.4 +/- 3.0 and 33.8 +/- 10.0), suggesting little effect on IP(3)-induced Ca(2+) release. To test the role of Ca2+ entry through membrane channels, after eliciting a transient Phe contraction in nominally 0 Ca(2+) Krebs, increasing concentrations of CaCl(2) (0.1, 0.3, 0.6, 1, 2.5 mM) were added and the extracellular Ca2+ concentration [Ca(2+)](e)-contraction relationship was constructed. The [Ca(2+)](e)-contraction relation was reduced in MMP-2 treated IVC, suggesting inhibition of Ca(2+) entry. In WC treated with MMP-2, the Ca(2+) channel blocker diltiazem (10(-5)M) did not cause any further inhibition of Phe contraction, suggesting that Ca(2+) entry is already inhibited by MMP-2. To test whether MMP-2 actions involve generation of RGD and modulation of integrin receptors, experiments where repeated in IVC segments saturated with RGD (10(-5) M), or pretreated with the alpha(v)beta(3) integrin blocker cyclo(Ala-Arg-Gly-Asp-3-aminomethylbenzoyl) (cyclo-RGD). RGD-peptide caused only small relaxation of Phe contracted IVC (6.4 +/- 3.4%), and addition of MMP-2 to RGD-treated IVC caused further relaxation (69.7 +/- 3.0%). Pretreatment of IVC with cyclo-RGD did not significantly affect MMP-2 induced relaxation (55.0 +/- 5.0%). Conclusions. In rat IVC, MMP-2 attenuates [Ca(2+)](e)-dependent VSM contraction without affecting Ca(2+) release from intracellular Ca(2+) stores. MMP-2 induced VSM relaxation may not involve RGD generation or activation of a(v)beta(3) integrin receptor. MMP-2 induced inhibition of the Ca(2+) entry mechanism of VSM contraction may play a role in the venous dilation associated with varicose vein formation. (C) 2010 Elsevier Inc. All rights reserved. C1 [Khalil, Raouf A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Vasc Surg, Boston, MA 02115 USA. [Khalil, Raouf A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Raffetto, Joseph D.] VA Boston Healthcare Syst, W Roxbury, MA USA. RP Khalil, RA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Vasc Surg, 75 Francis St, Boston, MA 02115 USA. EM raouf_khalil@hms.harvard.edu FU NHLBI NIH HHS [HL-65998, HL-70659, R01 HL065998, R01 HL065998-07A1, R01 HL065998-08, R01 HL070659, R01 HL070659-05] NR 51 TC 20 Z9 20 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD APR PY 2010 VL 159 IS 2 BP 755 EP 764 DI 10.1016/j.jss.2008.09.022 PG 10 WC Surgery SC Surgery GA 575MU UT WOS:000276072000023 PM 19482300 ER PT J AU Bergevin, C Shera, CA AF Bergevin, Christopher Shera, Christopher A. TI Coherent reflection without traveling waves: On the origin of long-latency otoacoustic emissions in lizards SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article DE acoustic wave reflection; harmonic oscillators; otoacoustic emissions; zoology ID AUDITORY-NERVE FIBERS; ALLIGATOR LIZARD; GEKKO-GECKO; TOKAY-GECKO; HAIR-CELLS; MIDDLE-EAR; FREESTANDING STEREOCILIA; SIGNAL TRANSMISSION; TONOTOPIC ORGANIZATION; BASILAR PAPILLA AB Lizard ears produce otoacoustic emissions with characteristics often strikingly reminiscent of those measured in mammals. The similarity of their emissions is surprising, given that lizards and mammals manifest major differences in aspects of inner ear morphology and function believed to be relevant to emission generation. For example, lizards such as the gecko evidently lack traveling waves along their basilar membrane. Despite the absence of traveling waves, the phase-gradient delays of gecko stimulus-frequency otoacoustic emissions (SFOAEs) are comparable to those measured in many mammals. This paper describes a model of emission generation inspired by the gecko inner ear. The model consists of an array of coupled harmonic oscillators whose effective damping manifests a small degree of irregularity. Model delays increase with the assumed sharpness of tuning, reflecting the build-up time associated with mechanical resonance. When tuning bandwidths are chosen to match those of gecko auditory-nerve fibers, the model reproduces the major features of gecko SFOAEs, including their spectral structure and the magnitude and frequency dependence of their phase-gradient delays. The same model with appropriately modified parameters reproduces the features of SFOAEs in alligator lizards. Analysis of the model demonstrates that the basic mechanisms operating in the model are similar to those of the coherent-reflection model developed to describe mammalian emissions. These results support the notion that SFOAE delays provide a noninvasive measure of the sharpness of cochlear tuning. C1 [Bergevin, Christopher] Univ Arizona, Dept Math, Tucson, AZ 85705 USA. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Shera, Christopher A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bergevin, C (reprint author), Univ Arizona, Dept Math, Tucson, AZ 85705 USA. FU Howard Hughes Medical Institute [52003749]; National Science Foundation Division of Mathematical Sciences [0602173]; NIDCD, National Institutes of Health [R01 DC003687] FX We thank Christine Koppl and Geoffrey Manley for providing us with the gecko auditory-nerve data. We also thank A. J. Aranyosi, Diek Duifhuis, John Guinan, Elizabeth Olson, and the anonymous reviewers for valuable comments and discussion. Our work was supported by the Howard Hughes Medical Institute (Grant No. 52003749), the National Science Foundation Division of Mathematical Sciences (Grant No. 0602173), and the NIDCD, National Institutes of Health (Grant No. R01 DC003687). NR 59 TC 23 Z9 23 U1 0 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD APR PY 2010 VL 127 IS 4 BP 2398 EP 2409 DI 10.1121/1.3303977 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 580DC UT WOS:000276426100046 PM 20370023 ER PT J AU Gallun, FJ AF Gallun, Frederick J. TI Judgments of intensity for brief sequences SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article DE acoustic intensity; acoustic intensity measurement; acoustic noise; hearing ID AUDITORY ATTENTIONAL BLINK; WORKING-MEMORY; DISCRIMINATION; FREQUENCY; MASKING; LEVEL; TIME AB The ability to make intensity judgments for sequential stimuli was examined with an intensity-discrimination task involving three 50-ms noise bursts with non-overlapping frequency ranges. Targets (single bursts) presented in three-burst sequences were required to be as much as 5 dB more intense than targets presented as single bursts in isolation, especially for the later targets. Randomizing target position in the sequence did not reliably reduce performance, nor were thresholds for younger and older listeners reliably different. These increases in increment detection threshold are indications of a specific intensity-processing deficit for stimuli occurring later in a sequence. C1 Portland VA Med Ctr, VA RR&D Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. RP Gallun, FJ (reprint author), Portland VA Med Ctr, VA RR&D Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM frederick.gallun@va.gov RI Gallun, Frederick/G-3792-2012 OI Gallun, Frederick/0000-0002-4145-2199 FU Department of Veterans Affairs; NIH FX This work was supported by the Department of Veterans Affairs and by the NIH. Stephen Fausti, Anna Diedesch, Michelle Molis, Marjorie Leek, Chris Mason, Virginia Best, Gerald Kidd, and Barbara Shinn-Cunningham provided helpful comments and guidance. Matthew Marble, Kelly Reavis, and Marc Caldwell helped with data collection. The greatest debt is to the participants. NR 18 TC 1 Z9 1 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD APR PY 2010 VL 127 IS 4 BP EL166 EP EL171 DI 10.1121/1.3359815 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 580DC UT WOS:000276426100008 PM 20369985 ER PT J AU Doyle, AE Biederman, J Ferreira, MAR Wong, P Smoller, JW Faraone, SV AF Doyle, Alysa E. Biederman, Joseph Ferreira, Manuel A. R. Wong, Patricia Smoller, Jordan W. Faraone, Stephen V. TI Suggestive Linkage of the Child Behavior Checklist Juvenile Bipolar Disorder Phenotype to 1p21, 6p21, and 8q21 SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE juvenile bipolar disorder; CBCL; genomewide linkage ID DEFICIT HYPERACTIVITY DISORDER; SCHIZOPHRENIA SUSCEPTIBILITY LOCI; GENOME-WIDE ASSOCIATION; CBCL; ADOLESCENTS; ADHD; SCAN; METAANALYSIS; PREVALENCE; DIAGNOSIS AB Objective: Several studies have documented a profile of elevated scores on the Attention Problems, Aggressive Behavior and Anxious/Depressed scales of the Child Behavior Checklist (CBCL) in youth with bipolar disorder. The sum of these scales, referred to as the CBCL Juvenile Bipolar Disorder (JBD) phenotype, has modest diagnostic utility, and high scores are associated with severity of psychopathology and poor outcome. Recently, a genomewide linkage scan of this measure in ADHD sibling pairs revealed a region of suggestive linkage on chromosome 2q21. The current study aimed to further identify quantitative trait loci that influence the CBCL-JBD phenotype by using a dense and thus, arguably, more powerful set of single-nucleotide polymorphism markers in a different ADHD sibling pair sample. Method: Subjects were 765 individuals from 154 families with CBCL data enrolled in a linkage study of ADHD. Linkage analyses were completed using a multipoint maximum likelihood variance components approach implemented using the statistical program SOLAR. Results: Heritability of the CBCL-JBD phenotype was estimated at .71. Although no regions of the genome surpassed empirically derived criteria for significant linkage (p = .000038), peaks on 1p21.1 (p = .00037; LOD = 2.76), 6p21.3 (p = .00054; LOD = 2.60), and 8q21.13 (p = .00081; LOD = 2.44) surpassed the threshold for suggestive linkage (p = .002). These regions have been highlighted in genomewide scans of bipolar disorder in adults, schizophrenia, autism, and ADHD. Conclusions: Findings raise the possibility that genes in these regions influence variation on the CBCL-JBD scale and the emotional and behavioral dysregulation associated with severe psychopathology. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(4):378-387. C1 [Doyle, Alysa E.; Biederman, Joseph; Smoller, Jordan W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Doyle, Alysa E.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet, Boston, MA 02114 USA. [Doyle, Alysa E.; Biederman, Joseph; Wong, Patricia] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Ferreira, Manuel A. R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY USA. RP Doyle, AE (reprint author), MGH WRN 705,55 Fruit St, Boston, MA 02114 USA. EM aedoyle@partners.org RI Ferreira, Manuel/D-3609-2013; OI Faraone, Stephen/0000-0002-9217-3982 FU MGH-Ryan Licht Sang Pediatric Bipolar Disorder Foundation Conference [R01HD37694, K08MH66072] FX This work was supported by R01HD37694 to Dr. Faraone and K08MH66072 to Dr. Doyle. Portions of this work were presented at the MGH-Ryan Licht Sang Pediatric Bipolar Disorder Foundation Conference, March 27, 2009, Cambridge, MA. NR 65 TC 15 Z9 15 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2010 VL 49 IS 4 BP 378 EP 387 DI 10.1016/j.jaac.2010.01.008 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 576OF UT WOS:000276153500011 PM 20410730 ER PT J AU Thrall, JH AF Thrall, James H. TI Health Care Reform in the Postrecession Economy SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St,Room 216, Boston, MA 02114 USA. EM jthrall@partners.org 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2010 VL 7 IS 4 BP 239 EP 240 DI 10.1016/j.jacr.2010.02.019 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SN UT WOS:000208362600001 PM 20362932 ER PT J AU Dighe, M Francis, IR Casalino, DD Arellano, RS Baumgarten, DA Curry, NS Fulgham, P Israel, GM Leyendecker, JR Papanicolaou, N Prasad, S Ramchandani, P Remer, EM Sheth, S AF Dighe, Manjiri Francis, Isaac R. Casalino, David D. Arellano, Ronald S. Baumgarten, Deborah A. Curry, Nancy S. Fulgham, Pat Israel, Gary M. Leyendecker, John R. Papanicolaou, Nicholas Prasad, Srinivasa Ramchandani, Parvati Remer, Erick M. Sheth, Sheila TI ACR Appropriateness Criteria (R) on Obstructive Voiding Symptoms Secondary to Prostate Disease SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness Criteria (R); prostate; benign prostate hyperplasia; voiding obstruction; bladder obstruction AB Obstructive voiding symptoms are most commonly due to prostatic hyperplasia, but other causes include bladder neck contractures, prostatic carcinomas, neurogenic bladder, and urethral stricture. Symptoms include hesitancy, dribbling, decreased force of stream, and postvoid fullness. Imaging is useful in evaluating the presence and degree of hydronephrosis, estimation of renal function, evaluation of the bladder and prostate, and detection of incidental upper tract malignancies or stones. Various modalities have been used for evaluation of the cause of obstruction. Literature on the indications and usefulness of these radiologic studies for obstructive voiding symptoms in different clinical settings is reviewed. C1 [Dighe, Manjiri] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Francis, Isaac R.] Univ Michigan, Ann Arbor, MI 48109 USA. [Casalino, David D.] Northwestern Univ, Chicago, IL 60611 USA. [Arellano, Ronald S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baumgarten, Deborah A.] Emory Univ Hosp, Atlanta, GA 30322 USA. [Curry, Nancy S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Fulgham, Pat] Presbyterian Med Ctr, Dallas, TX USA. [Fulgham, Pat] Amer Urol Assoc, Linthicum, MD USA. [Israel, Gary M.] Yale Univ, Sch Med, New Haven, CT USA. [Leyendecker, John R.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Papanicolaou, Nicholas; Ramchandani, Parvati] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Prasad, Srinivasa] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Remer, Erick M.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Sheth, Sheila] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Dighe, M (reprint author), Univ Washington, Med Ctr, Dept Radiol, 1959 NE Pacific St,Box 357115, Seattle, WA 98195 USA. EM dighe@u.washington.edu NR 35 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2010 VL 7 IS 4 BP 255 EP 259 DI 10.1016/j.jacr.2009.12.004 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SN UT WOS:000208362600008 PM 20362939 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI The Recent US Preventive Services Task Force Guidelines Are Not Supported by the Scientific Evidence and Should Be Rescinded SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Breast cancer; mammography screening; screening guidelines AB The recent US Preventive Services Task Force (USPSTF) guidelines on mammographic screening ignore the scientific evidence and should be rescinded. There are no data to support the age of 50 years as a threshold for screening. There are no data to support screening women aged 40 to 49 years on the basis of risk. The USPSTF failed to understand the randomized controlled trials and used the lowest possible benefit in its calculations. The death rate from breast cancer has decreased by 30%, primarily because of screening. The agency ignored direct data with regard to decreasing deaths in real populations in favor of computer models. The USPSTF admits that its guidelines will result in unnecessary deaths from breast cancer that could be avoided by screening annually beginning at the age of 40 years. C1 [Kopans, Daniel B.] Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Div, Boston, MA 02114 USA. [Kopans, Daniel B.] Harvard Univ, Sch Med, Boston, MA USA. RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Div, 55 Fruit St, Boston, MA 02114 USA. EM dkopans@partners.org NR 31 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2010 VL 7 IS 4 BP 260 EP 264 DI 10.1016/j.jacr.2009.12.008 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SN UT WOS:000208362600009 PM 20362940 ER PT J AU Batlle, JC Hahn, PF Thrall, JH Lee, SI AF Batlle, Juan C. Hahn, Peter F. Thrall, James H. Lee, Susanna I. TI Patients Imaged Early During Admission Demonstrate Reduced Length of Hospital Stay: A Retrospective Cohort Study of Patients Undergoing Cross-Sectional Imaging SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Utilization; cross-sectional imaging; length of stay; inpatient AB Purpose: The aim of this study was to relate the early use of advanced imaging to length of hospital stay. Materials and Methods: Among all 33,226 admissions to an urban tertiary care hospital in 2005, the authors identified the 10,005 admissions (30.1%) that included >= 1 advanced imaging study (CT, MRI, or nuclear scintigraphy) during the period from 1 day before admission (day -1) through discharge. The length of stay was calculated, and using the date of the first advanced imaging study performed relative to date of admission (date of service), the residual length of stay (length of stay minus date of service) of each admission was also calculated. For admissions of >= 3 days in duration, the mean length of stay of patients with early imaging (on day -1 or 0) was compared using t test to that of patients with later imaging (on day 1 or 2). For all admissions with advanced imaging, linear regression analysis was applied to length of stay and residual length of stay as a function of date of service. Similar analysis was performed on subgroups classified by examination type (modality and body part) and International Classification of Diseases, Ninth Revision (ICD-9) diagnostic code. Results: The mean length of stay was significantly shorter for those imaged on day -1 or 0 compared with day 1 or 2 for all admissions of >= 3 days (8.6 vs 9.0 days, P = .015) and for the following specific subgroups: abdominal CT (8.4 vs 9.7 days, P = .003) and neurologic MR examination types (7.6 vs 8.7 days, P = .03) and abdominal ICD-9 codes (7.5 vs 8.8 days, P = .007). A statistically significant positive correlation was noted between length of stay and date of service for all admissions (slope, 0.27; P < .001) and for the following subgroups: neurologic CT, chest CT, abdominal CT, and nuclear scintigraphy examination types and abdominal ICD-9 codes. Conclusion: Early imaging with CT, MRI, or nuclear scintigraphy, particularly on the day before or the day of admission, was associated with significantly shorter lengths of stay of inpatients compared with patients who underwent advanced imaging later. C1 [Batlle, Juan C.; Hahn, Peter F.; Thrall, James H.; Lee, Susanna I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Batlle, JC (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM jbatlle@partners.org NR 7 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2010 VL 7 IS 4 BP 269 EP 276 DI 10.1016/j.jacr.2009.11.024 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SN UT WOS:000208362600011 PM 20362942 ER PT J AU Ding, A Mueller, PR AF Ding, Alexander Mueller, Peter R. TI The Breadth of Teaching Commitment in Radiology Departments: A National Survey SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Education; funding; teaching; academic time AB Purpose: The aim of this study was to investigate the teaching effort and associated resources across variously sized academic and nonacademic hospitals across the country. Methods: A simple survey was constructed and distributed nationally to academic and nonacademic radiology departments of attending-level radiologists with residency programs. The survey queried human and financial resources used for education in the department or division in comparison with compensated human and financial resources for this effort. Results: Sixty institutions across the country were surveyed, with 40 surveys returned from 35 unique institutions, representing a 67% response rate. All respondents reported performing teaching duties. The average teaching in departments was 30 hours per week, including teaching a wide scope of constituents, including trainees, colleagues, and allied staff members. The majority of teaching was spent on teaching medical students, residents, and fellows as well as referring physicians at multidisciplinary rounds. The commitment of dedicated full-time equivalent staff members and funding to teaching was limited, with 45% of respondents without dedicated full-time equivalents for teaching and just over 7% of the teaching funded. Eighty percent of institutions surveyed provided some amount of weekly academic time during which many staff members carried out their teaching preparations. Conclusions: Respondent radiology departments reported significant resource and manpower allocations to teaching efforts, in particular to trainees and referring physicians. However, limited compensation or incentives are allocated to this effort with regard to both human and financial resources. Compensated, allotted staff academic time may help offset the lack of dedicated educational resources to the teaching effort of radiology departments. C1 [Ding, Alexander; Mueller, Peter R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Ding, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Founders House 216,55 Fruit St, Boston, MA 02114 USA. EM ading1@partners.org NR 1 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2010 VL 7 IS 4 BP 290 EP 293 DI 10.1016/j.jacr.2009.10.018 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SN UT WOS:000208362600014 PM 20362945 ER PT J AU Hsu, J Price, M Fung, V Brand, R Bertko, J Newhouse, J AF Hsu, J. Price, M. Fung, V. Brand, R. Bertko, J. Newhouse, J. TI The Medicare Part D Coverage Gap: Drug Use and Adherence Among Patients With High Out-of-Pocket Expenditures SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Hsu, J.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Price, M.; Fung, V.] Kaiser Permanente CHPS, Oakland, CA USA. [Price, M.; Fung, V.] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. [Brand, R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bertko, J.] RAND, Santa Monica, CA USA. [Hsu, J.; Newhouse, J.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 5 EP 6 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100015 ER PT J AU Ganz, DA Koretz, BK McCreath, HE Wenger, NS Roth, CP Bail, JK Reuben, DB AF Ganz, D. A. Koretz, B. K. McCreath, H. E. Wenger, N. S. Roth, C. P. Bail, J. K. Reuben, D. B. TI The Effect of Nurse Practitioner Co-Management on Quality of Care of Patients with Chronic Conditions in an Academic Geriatric Practice SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Ganz, D. A.; Koretz, B. K.; McCreath, H. E.; Wenger, N. S.; Bail, J. K.; Reuben, D. B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ganz, D. A.] VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Excellence, Los Angeles, CA USA. [Roth, C. P.] RAND Hlth, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 8 EP 8 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100021 ER PT J AU Kostas, TR Bernacki, RE AF Kostas, T. R. Bernacki, R. E. TI A Multipronged Approach to Improving Geriatric Competency in Internal Medicine Residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Kostas, T. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bernacki, R. E.] BWH, DFCI, Div Aging, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 9 EP 9 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100024 ER PT J AU Sarkisian, C Trejo, L Wang, P Frank, J Weiner, B AF Sarkisian, C. Trejo, L. Wang, P. Frank, J. Weiner, B. TI Caminemos !: a randomized trial of a behavioral intervention to increase walking among older Latinos SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Sarkisian, C.] GRECC, VA Greater Los Angeles, Los Angeles, CA USA. [Sarkisian, C.; Wang, P.; Frank, J.] Univ Calif Los Angeles, Div Geriatr, Los Angeles, CA 90024 USA. [Weiner, B.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Trejo, L.] City Los Angeles, Dept Aging, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 15 EP 15 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100041 ER PT J AU Williams, BA Mehta, KM Cenzer, IS Walter, LC AF Williams, B. A. Mehta, K. M. Cenzer, I. Stijacic Walter, L. C. TI Wealth and the appropriate use of PSA screening among older men SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Williams, B. A.; Mehta, K. M.; Cenzer, I. Stijacic; Walter, L. C.] UCSF, Div Geriatr, San Francisco, CA USA. [Williams, B. A.; Mehta, K. M.; Walter, L. C.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 15 EP 16 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100042 ER PT J AU Kaiser, SA Wang, PC Meltzer, C Weiner, B Sarkisian, CA AF Kaiser, S. A. Wang, P. C. Meltzer, C. Weiner, B. Sarkisian, C. A. TI Tiene Razon!: Older Latinos who Change their Attributions for Exercising are More Likely to Experience Sustained Increases in Physical Activity SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Kaiser, S. A.] VA Boston Healthcare Syst, GRECC, Boston, MA USA. [Kaiser, S. A.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Sarkisian, C. A.] VA Greater Los Angeles, GRECC, Los Angeles, CA USA. [Meltzer, C.; Sarkisian, C. A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 17 EP 17 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100046 ER PT J AU Ross, JS Reed, KC AF Ross, J. S. Reed, K. C. TI Intranasal Steroid Induced Psychosis In A Geriatric Patient SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Ross, J. S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Ross, J. S.; Reed, K. C.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 19 EP 19 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100051 ER PT J AU Manoff, S McFetridge, R Liss, C Marchese, R Raab, J Rueda, A Musher, D AF Manoff, S. McFetridge, R. Liss, C. Marchese, R. Raab, J. Rueda, A. Musher, D. TI Antibody Persistence 10 Years after 1st and 2nd Doses of 23-Valent Pneumococcal Polysaccharide Vaccine (PN23), and Immunogenicity and Safety of 2nd and 3rd Doses in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Manoff, S.; McFetridge, R.; Liss, C.; Marchese, R.] Merck, N Wales, PA USA. [Raab, J.] PPD, Wayne, NJ USA. [Rueda, A.; Musher, D.] VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 25 EP 26 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100071 ER PT J AU Sanchez-Reilly, S Ross, J O'Donnell, L Lee, S Schillerstrom, J AF Sanchez-Reilly, S. Ross, J. O'Donnell, L. Lee, S. Schillerstrom, J. TI A Longitudinal Curriculum in Geriatric Palliative Care for Medical Students SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Sanchez-Reilly, S.; Ross, J.; O'Donnell, L.; Schillerstrom, J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sanchez-Reilly, S.; Ross, J.; Lee, S.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 44 EP 44 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100126 ER PT J AU Horton, MS Pugh, M Lawrence, VA AF Horton, M. S. Pugh, M. Lawrence, V. A. TI Nonpharmacological Therapy for Insomnia in Elders: A Systematic SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Horton, M. S.] Univ Texas Hlth Sci Ctr San Antonio, VA Univ, San Antonio, TX 78229 USA. [Pugh, M.; Lawrence, V. A.] S Texas Vet Hlth Care Syst, VERDICT REAP, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 65 EP 65 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100187 ER PT J AU Hsu, A Sudore, R Doughan, J Williams, B AF Hsu, A. Sudore, R. Doughan, J. Williams, B. TI When Caring Costs More. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Hsu, A.; Sudore, R.; Williams, B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hsu, A.; Sudore, R.; Doughan, J.; Williams, B.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 78 EP 78 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100224 ER PT J AU Zanin, N Jones, R Marcantonio, E Rudolph, J Fong, T Yang, F Yap, L Inouye, S AF Zanin, N. Jones, R. Marcantonio, E. Rudolph, J. Fong, T. Yang, F. Yap, L. Inouye, S. TI Hospitalization in Community-Dwelling Persons with Alzheimer's Disease. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Marcantonio, E.; Fong, T.; Yang, F.; Inouye, S.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Zanin, N.; Jones, R.; Marcantonio, E.; Rudolph, J.; Fong, T.; Yang, F.; Inouye, S.] Aging Brain Ctr, Boston, MA USA. [Yap, L.] MADRC MGH, Boston, MA USA. [Zanin, N.] Wright State Univ SOM, Dayton, OH USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 87 EP 87 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100250 ER PT J AU Givens, J Prigerson, HG Jones, RN Mitchell, SL AF Givens, J. Prigerson, H. G. Jones, R. N. Mitchell, S. L. TI Health Care Proxies Exposure to Distressing Symptoms Experienced by Their Loved Ones with Advanced Dementia. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Givens, J.; Jones, R. N.; Mitchell, S. L.] Inst Aging Res, Boston, MA USA. [Prigerson, H. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 89 EP 89 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100255 ER PT J AU Pham, A Datta, S Weber, T Walter, L Colon-Emeric, C AF Pham, A. Datta, S. Weber, T. Walter, L. Colon-Emeric, C. TI Cost-effectiveness of Oral Bisphosphonates for Osteoporosis at Different Ages and Levels of Life Expectancy. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Pham, A.; Weber, T.] Duke Univ, Med Ctr, Durham, NC USA. [Datta, S.] Duke Univ, Gen Internal Med, Durham, NC USA. [Datta, S.] Durham VA Med Ctr, Ctr Hlth Serv Res, Durham, NC USA. [Walter, L.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Colon-Emeric, C.] Durham VA Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 97 EP 98 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100279 ER PT J AU Hirano, LA Anawalt, BD Shields, AT Matsumoto, AM AF Hirano, L. A. Anawalt, B. D. Shields, A. T. Matsumoto, A. M. TI Evaluation and Treatment of Osteoporosis in High Risk Veterans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Hirano, L. A.; Anawalt, B. D.; Shields, A. T.; Matsumoto, A. M.] Univ Washington, Seattle, WA 98195 USA. [Hirano, L. A.; Shields, A. T.; Matsumoto, A. M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 101 EP 102 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100291 ER PT J AU Steinman, MA Fung, K Boscardin, J Heidenreich, PA AF Steinman, M. A. Fung, K. Boscardin, J. Heidenreich, P. A. TI Age and receipt of guideline-recommended care for heart failure: a nationwide study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Steinman, M. A.; Fung, K.; Boscardin, J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Heidenreich, P. A.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 113 EP 114 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100326 ER PT J AU Jeffery, S Aspinall, SL Zhao, X Handler, SM Hanlon, JT AF Jeffery, S. Aspinall, S. L. Zhao, X. Handler, S. M. Hanlon, J. T. TI The Quality of Warfarin Prescribing and Monitoring in Veterans Affairs Nursing Homes. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Jeffery, S.] VA Connecticut Healthcare Syst, Dept Pharm, West Haven, CT USA. [Aspinall, S. L.; Zhao, X.] VA Ctr Medicat Safety, Hines, IL USA. [Aspinall, S. L.; Zhao, X.] VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Handler, S. M.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Handler, S. M.; Hanlon, J. T.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 114 EP 114 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100328 ER PT J AU Dinescu, A Korc-Grodzicki, B Ross, JS AF Dinescu, A. Korc-Grodzicki, B. Ross, J. S. TI Discharge Location Disagreements and Re-hospitalization Risk among Frail, Elderly Adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Dinescu, A.; Ross, J. S.] Mt Sinai Hosp, New York, NY 10029 USA. [Korc-Grodzicki, B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ross, J. S.] James J Peters VA Med Ctr, Bronx, NY USA. [Ross, J. S.] James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 115 EP 115 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100331 ER PT J AU Dublin, S Anderson, ML Heckbert, SR Haneuse, SJ Crane, PK Breitner, JC McCormick, W Bowen, JD Teri, L McCurry, SM Larson, EB AF Dublin, S. Anderson, M. L. Heckbert, S. R. Haneuse, S. J. Crane, P. K. Breitner, J. C. McCormick, W. Bowen, J. D. Teri, L. McCurry, S. M. Larson, E. B. TI Atrial fibrillation and risk of incident dementia or Alzheimer's disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Dublin, S.; Anderson, M. L.; Heckbert, S. R.; Haneuse, S. J.; McCurry, S. M.; Larson, E. B.] Grp Hlth Res Inst, Seattle, WA USA. [Dublin, S.; Heckbert, S. R.; Haneuse, S. J.; Crane, P. K.; Breitner, J. C.; McCormick, W.; Bowen, J. D.; Teri, L.; McCurry, S. M.; Larson, E. B.] Univ Washington, Seattle, WA 98195 USA. [Breitner, J. C.] VA Puget Sound, Seattle, WA USA. [Bowen, J. D.] Swedish Neurosci Inst, Seattle, WA USA. RI Crane, Paul/C-8623-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 122 EP 123 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100352 ER PT J AU Huang, A Brown, J Moore, E Walter, L Scholes, D Lin, F Fihn, S AF Huang, A. Brown, J. Moore, E. Walter, L. Scholes, D. Lin, F. Fihn, S. TI Clinical significance of postvoid residual volume in older women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Huang, A.; Brown, J.; Walter, L.; Lin, F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Brown, J.; Walter, L.] SFVAMC, San Francisco, CA USA. [Moore, E.; Fihn, S.] Univ Washington, Seattle, WA 98195 USA. [Scholes, D.] Grp Hlth Res Inst, Seattle, WA USA. [Scholes, D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 123 EP 123 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100354 ER PT J AU Means, A Martin, J Fiorentino, L Chung, C Josephson, K Jouldjian, S Alessi, C AF Means, A. Martin, J. Fiorentino, L. Chung, C. Josephson, K. Jouldjian, S. Alessi, C. TI Sleep Disorders Among Older Veterans Undergoing Inpatient Post-Acute Rehabilitation SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Means, A.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Martin, J.; Josephson, K.; Jouldjian, S.; Alessi, C.] VA Greater Los Angeles, GRECC, Los Angeles, CA USA. [Martin, J.; Fiorentino, L.; Chung, C.; Alessi, C.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 127 EP 127 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100366 ER PT J AU Michael, JT Abdel-Karim, IA AF Michael, J. T. Abdel-Karim, I. A. TI Tolerance of cancer drug trials in different geriatric populations. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Michael, J. T.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX 78229 USA. [Abdel-Karim, I. A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol & Med Oncol, San Antonio, TX 78229 USA. [Abdel-Karim, I. A.] S Texas Vet Hlth Care Syst, Hematol & Oncol, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 144 EP 144 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100416 ER PT J AU Lycett, ES Schaefer, KG Bernacki, RE AF Lycett, E. S. Schaefer, K. G. Bernacki, R. E. TI Inpatient Palliative Care Consultation for Patients with Advanced Heart Failure. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Lycett, E. S.] Univ Vermont, Coll Med, Burlington, VT USA. [Lycett, E. S.] Harvard Univ, Sch Med, Boston, MA USA. [Schaefer, K. G.; Bernacki, R. E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Schaefer, K. G.; Bernacki, R. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 165 EP 165 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100477 ER PT J AU Key, C Lee, S Garza, M Sanchez-Reilly, SE AF Key, C. Lee, S. Garza, M. Sanchez-Reilly, S. E. TI Impact of a geriatric consultation on the prescription of potentially inappropriate medications and opioids in elderly patients. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Key, C.; Garza, M.; Sanchez-Reilly, S. E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Key, C.; Lee, S.; Sanchez-Reilly, S. E.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 170 EP 170 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100492 ER PT J AU Chester, JG Harrington, M Rudolph, JL AF Chester, J. G. Harrington, M. Rudolph, J. L. TI Nighttime Vital Signs: Do They Change Management? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Chester, J. G.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Harrington, M.; Rudolph, J. L.] VA Boston Healthcare Syst, GRECC, Boston, MA USA. [Rudolph, J. L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 173 EP 173 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100499 ER PT J AU Wenger, NS Roth, CP Martin, DC Nickels, LD Mach, J Ganz, DA AF Wenger, N. S. Roth, C. P. Martin, D. C. Nickels, L. D. Mach, J. Ganz, D. A. TI Quality of Care Provided in a Special Needs Plan Using a Nurse Care Manager Model. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Wenger, N. S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Wenger, N. S.; Roth, C. P.; Ganz, D. A.] RAND Hlth, Santa Monica, CA USA. [Ganz, D. A.] VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Excellence, Los Angeles, CA USA. [Mach, J.] XL Hlth, Baltimore, MD USA. [Martin, D. C.; Nickels, L. D.] Ovations, UnitedHlth Grp, Minneapolis, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 175 EP 175 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100505 ER PT J AU Lin, JC Bang, J Moore, AA AF Lin, J. C. Bang, J. Moore, A. A. TI Drinking Patterns and Development of Functional Limitations Among Older Adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Lin, J. C.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lin, J. C.; Moore, A. A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Moore, A. A.] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90095 USA. [Bang, J.] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 180 EP 180 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100520 ER PT J AU Davila, AE Garza, M Lee, S Ross, JS Sanchez-Reilly, S AF Davila, A. E. Garza, M. Lee, S. Ross, J. S. Sanchez-Reilly, S. TI Effectiveness of a Geriatric Palliative Care Consult on Pain and Geriatric Syndromes. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Davila, A. E.; Garza, M.; Ross, J. S.; Sanchez-Reilly, S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Garza, M.; Lee, S.; Ross, J. S.; Sanchez-Reilly, S.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 185 EP 186 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100536 ER PT J AU Gestuvo, M Lindenberger, E AF Gestuvo, M. Lindenberger, E. TI Skin Hazards of Hospitalization Beyond Pressure Ulcers. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Gestuvo, M.] Mt Sinai Sch Med, New York, NY USA. [Lindenberger, E.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 196 EP 196 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100567 ER PT J AU Patel, NK Copeland, LA Parchman, ML Lawrence, VA AF Patel, N. K. Copeland, L. A. Parchman, M. L. Lawrence, V. A. TI Physical activity, functioning and length of stay in older diabetes patients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Patel, N. K.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Copeland, L. A.; Parchman, M. L.; Lawrence, V. A.] Dept Vet Affairs, VERDICT Res, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 226 EP 226 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100657 ER PT J AU Bowling, B Sawlyer, P Allman, RM AF Bowling, B. Sawlyer, P. Allman, R. M. TI Anemia and Functional Decline in Community-Dwelling Older Adults with Chronic Kidney Disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Bowling, B.; Sawlyer, P.; Allman, R. M.] Univ Alabama, Birmingham, AL USA. [Bowling, B.; Allman, R. M.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 234 EP 234 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100681 ER PT J AU Nyaggah, E Roberts, CK Greenberg, G Hahn, TJ Lee, CC AF Nyaggah, E. Roberts, C. K. Greenberg, G. Hahn, T. J. Lee, C. C. TI Is physical activity in older men associated with serum testosterone and sex hormone-binding globulin levels? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Nyaggah, E.; Greenberg, G.; Hahn, T. J.; Lee, C. C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Roberts, C. K.] Univ Calif Los Angeles, Dept Physiol Sci Epidemiol, Los Angeles, CA USA. [Roberts, C. K.] Univ Calif Los Angeles, Ctr Metab Dis Prevent, Los Angeles, CA USA. [Greenberg, G.; Hahn, T. J.; Lee, C. C.] Vet Affairs Greater Los Angeles Healthcare Syst, Internal Med GRECC, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 236 EP 236 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100686 ER PT J AU Andrews, C Sanchez-Reilly, S Lee, S Ross, J AF Andrews, C. Sanchez-Reilly, S. Lee, S. Ross, J. TI Advance Directives Among Older Adults Seen In Geriatric Palliative Care And Internal Medicine Clinics SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Andrews, C.; Sanchez-Reilly, S.; Ross, J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sanchez-Reilly, S.; Lee, S.; Ross, J.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 240 EP 240 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100698 ER PT J AU Rudolph, JL Inouye, SK Jones, RN Yang, FM Fong, TG Levkoff, SE Marcantonio, ER AF Rudolph, James L. Inouye, Sharon K. Jones, Richard N. Yang, Frances M. Fong, Tamara G. Levkoff, Sue E. Marcantonio, Edward R. TI Delirium: An Independent Predictor of Functional Decline After Cardiac Surgery SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE delirium; function; cardiac surgery; aged; instrumental activities of daily living ID CONFUSION ASSESSMENT METHOD; POSTOPERATIVE DELIRIUM; INSTRUMENTAL ACTIVITIES; HIP FRACTURE; RELIABILITY; PATIENT; VALIDATION; PEOPLE; SCALE; RULE AB OBJECTIVES To determine whether patients who developed delirium after cardiac surgery were at risk of functional decline. DESIGN Prospective cohort study. SETTING Two academic hospitals and a Veterans Affairs Medical Center. PARTICIPANTS One hundred ninety patients aged 60 and older undergoing elective or urgent cardiac surgery. MEASUREMENTS Delirium was assessed daily and was diagnosed according to the Confusion Assessment Method. Before surgery and 1 and 12 months postoperatively, patients were assessed for function using the instrumental activities of daily living (IADL) scale. Functional decline was defined as a decrease in ability to perform one IADL at follow-up. RESULTS Delirium occurred in 43.1% (n=82) of the patients (mean age 73.7 +/- 6.7). Functional decline occurred in 36.3% (n=65/179) at 1 month and in 14.6% (n=26/178) at 12 months. Delirium was associated with greater risk of functional decline at 1 month (relative risk (RR)=1.9, 95% confidence interval (CI)=1.3-2.8) and tended toward greater risk at 12 months (RR=1.9, 95% CI=0.9-3.8). After adjustment for age, cognition, comorbidity, and baseline function, delirium remained significantly associated with functional decline at 1 month (adjusted RR=1.8, 95% CI=1.2-2.6) but not at 12 months (adjusted RR=1.5, 95% CI=0.6-3.3). CONCLUSION Delirium was independently associated with functional decline at 1 month and had a trend toward association at 12 months. These findings provide justification for intervention trials to evaluate whether delirium prevention or treatment strategies might improve postoperative functional recovery. C1 [Rudolph, James L.] VABHS, Ctr Geriatr Res Educ & Clin, Boston, MA 02130 USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Yang, Frances M.; Levkoff, Sue E.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Rudolph, James L.; Inouye, Sharon K.; Jones, Richard N.; Yang, Frances M.; Fong, Tamara G.; Levkoff, Sue E.; Marcantonio, Edward R.] Harvard Univ, Sch Med, Boston, MA USA. [Inouye, Sharon K.; Yang, Frances M.; Marcantonio, Edward R.] Hebrew SeniorLife, Aging Brain Ctr, Boston, MA USA. [Inouye, Sharon K.; Jones, Richard N.; Yang, Frances M.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Gen Med, Boston, MA 02215 USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Primary Care, Boston, MA 02215 USA. [Fong, Tamara G.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Inouye, Sharon K.; Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Dept Gerontol, Boston, MA 02215 USA. RP Rudolph, JL (reprint author), VABHS, Ctr Geriatr Res Educ & Clin, 150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X FU Harvard Older Americans Independence Center [P30-AG08812, R03-AG029861, K24-G00949, R21-AG0 27549, R21-AG026566]; National Institute on Aging; Alzheimer's Association [IIRG-09-88737]; Veterans Affairs Rehabilitation Career Development Award FX This work was funded by the Harvard Older Americans Independence Center P30-AG08812 (ERM, RNJ), R03-AG029861 (JLR), K24-G00949 (SKI), R21-AG0 27549 (ERM), and R21-AG026566 (ERM) from the National Institute on Aging and Grant IIRG-09-88737 (SKI) from the Alzheimer's Association. Dr. Rudolph is supported by a Veterans Affairs Rehabilitation Career Development Award. NR 29 TC 96 Z9 101 U1 3 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 IS 4 BP 643 EP 649 DI 10.1111/j.1532-5415.2010.02762.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TN UT WOS:000276247000003 PM 20345866 ER PT J AU Jennings, LA Auerbach, AD Maselli, J Pekow, PS Lindenauer, PK Lee, SJ AF Jennings, Lee A. Auerbach, Andrew D. Maselli, Judith Pekow, Penelope S. Lindenauer, Peter K. Lee, Sei J. TI Missed Opportunities for Osteoporosis Treatment in Patients Hospitalized for Hip Fracture SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 32nd Annual National Meeting of the Society-for-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med (SGIM) DE osteoporosis; hip fracture; calcium; vitamin D ID RANDOMIZED CONTROLLED-TRIAL; MAJOR NONCARDIAC SURGERY; BONE-MINERAL DENSITY; SUBSEQUENT FRACTURE; FRAGILITY FRACTURE; PREVENT FRACTURES; ZOLEDRONIC ACID; MORTALITY; MEN; MANAGEMENT AB OBJECTIVES Although osteoporosis treatment can dramatically reduce fracture risk, rates of treatment after hip fracture remain low. In-hospital initiation of recommended medications has improved outcomes in heart disease; hospitalization for hip fracture may represent a similar opportunity for improvement. The objective of this study was to examine rates of in-hospital treatment with a combination of calcium and vitamin D (Cal+D) and antiresorptive or bone-forming medications in patients hospitalized for hip fractures DESIGN Observational cohort. SETTING Three hundred eighteen hospitals in the United States. PARTICIPANTS Fifty-one thousand three hundred forty-six patients aged 65 and older hospitalized for osteoporotic hip fracture. MEASUREMENTS In-hospital administration of Cal+D and antiresorptive or bone-forming medications. RESULTS Three thousand four hundred five patients (6.6%) received Cal+D anytime after a procedure to correct femoral fracture; 3,763 patients (7.3%) received antiresorptive or bone-forming medications. Only 1,023 patients (2.0%) were prescribed ideal therapy, receiving Cal+D and an antiresorptive or bone-forming medication. Treatment rates remained low across virtually all patient-, provider-, and hospital-level characteristics. The strongest predictor of treatment with Cal+D was the receipt of an antiresorptive or bone-forming medication (adjusted odds ratio=5.50, 95% confidence interval=4.84-6.25), but only 27.2% of patients who received these medications also received Cal+D. CONCLUSION Rates of in-hospital initiation of osteoporosis treatment for patients with hip fracture are low and may represent an opportunity to improve care. C1 [Jennings, Lee A.] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Auerbach, Andrew D.; Maselli, Judith] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94121 USA. [Pekow, Penelope S.; Lindenauer, Peter K.] Tufts Univ, Sch Med, Baystate Med Ctr, Ctr Qual & Safety Res, Boston, MA 02111 USA. [Pekow, Penelope S.; Lindenauer, Peter K.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Lee, Sei J.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. RP Jennings, LA (reprint author), Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, 4150 Clement St,Bldg 203,Rm 1A-87, San Francisco, CA 94121 USA. EM lee.jennings@ucsf.edu FU NCRR NIH HHS [KL2 RR024130, KL2 RR024130-04, KL2 RR024130-048738, KL2RR024130]; NHLBI NIH HHS [R01 HL086473, 5R01HL086473, R01 HL086473-03]; NIA NIH HHS [5R21AG026668, L30 AG030755, L30 AG030755-02, R21 AG026668, R21 AG026668-02] NR 48 TC 55 Z9 59 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 IS 4 BP 650 EP 657 DI 10.1111/j.1532-5415.2010.02769.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TN UT WOS:000276247000004 PM 20398147 ER PT J AU Xia, Y Babitt, JL Bouley, R Zhang, Y Da Silva, N Chen, SZ Zhuang, ZJ Samad, TA Brenner, GJ Anderson, JL Hong, CC Schneyer, AL Brown, D Lin, HY AF Xia, Yin Babitt, Jodie L. Bouley, Richard Zhang, Ying Da Silva, Nicolas Chen, Shanzhuo Zhuang, Zhenjie Samad, Tarek A. Brenner, Gary J. Anderson, Jennifer L. Hong, Charles C. Schneyer, Alan L. Brown, Dennis Lin, Herbert Y. TI Dragon Enhances BMP Signaling and Increases Transepithelial Resistance in Kidney Epithelial Cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; MORPHOGENETIC PROTEIN CORECEPTOR; REGULATES HEPCIDIN EXPRESSION; TIGHT JUNCTION PROTEIN; TGF-BETA SUPERFAMILY; IN-VIVO; INTERCALATED CELLS; MEMBRANE-PROTEINS; GENE-EXPRESSION; URETERAL BUD AB The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology. C1 [Xia, Yin; Babitt, Jodie L.; Bouley, Richard; Zhang, Ying; Da Silva, Nicolas; Chen, Shanzhuo; Zhuang, Zhenjie; Anderson, Jennifer L.; Brown, Dennis; Lin, Herbert Y.] Harvard Univ, Program Membrane Biol, Ctr Syst Biol, Sch Med, Boston, MA 02114 USA. [Xia, Yin; Babitt, Jodie L.; Bouley, Richard; Zhang, Ying; Da Silva, Nicolas; Chen, Shanzhuo; Zhuang, Zhenjie; Anderson, Jennifer L.; Brown, Dennis; Lin, Herbert Y.] Harvard Univ, Sch Med, Div Nephrol, Dept Med, Boston, MA 02114 USA. [Samad, Tarek A.; Brenner, Gary J.] Harvard Univ, Sch Med, Neural Plast Res Unit, Massachusetts Gen Hosp,Dept Anesthesia, Boston, MA 02114 USA. [Hong, Charles C.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN USA. [Schneyer, Alan L.] Harvard Univ, Massachusetts Gen Hosp, Reprod Endocrine Unit, Sch Med,Dept Med, Boston, MA 02114 USA. RP Lin, HY (reprint author), Harvard Univ, Program Membrane Biol, Ctr Syst Biol, Sch Med, 185 Cambridge St,CPZN 8216, Boston, MA 02114 USA. EM Lin.Herbert@mgh.harvard.edu RI Hong, Charles/C-9989-2010 FU National Institutes of Health (NIH) [RO1 DK-071837, RO1 DK-069533, DK-42956, R03HD60641, K08 DK-075846] FX H.Y.L. was supported by National Institutes of Health (NIH) grant RO1 DK-071837 and RO1 DK-069533. D.B. was supported by NIH grant DK-42956. Y.X. was supported by NIH grant R03HD60641. J.L.B. was supported by NIH grant K08 DK-075846. The authors thank David A. Fabizio and Jason Campagna for technical assistance. NR 62 TC 19 Z9 20 U1 0 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2010 VL 21 IS 4 BP 666 EP 677 DI 10.1681/ASN.2009050511 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 584WQ UT WOS:000276784800019 PM 20167703 ER PT J AU Ajani, JA Barthel, JS Bekaii-Saab, T Bentrem, DJ D'Amico, TA Das, P Denlinger, C Fuchs, CS Gerdes, H Hayman, JA Hazard, L Hofstetter, WL Ilson, DH Keswani, RN Kleinberg, LR Korn, M Meredith, K Mulcahy, MF Orringer, MB Osarogiagbon, RU Posey, JA Sasson, AR Scott, WJ Shibata, S Strong, VEM Washington, MK Willett, C Wood, DE Wright, CD Yang, G AF Ajani, Jaffer A. Barthel, James S. Bekaii-Saab, Tanios Bentrem, David J. D'Amico, Thomas A. Das, Prajnan Denlinger, Crystal Fuchs, Charles S. Gerdes, Hans Hayman, James A. Hazard, Lisa Hofstetter, Wayne L. Ilson, David H. Keswani, Rajesh N. Kleinberg, Lawrence R. Korn, Michael Meredith, Kenneth Mulcahy, Mary F. Orringer, Mark B. Osarogiagbon, Raymond U. Posey, James A. Sasson, Aaron R. Scott, Walter J. Shibata, Stephen Strong, Vivian E. M. Washington, Mary Kay Willett, Christopher Wood, Douglas E. Wright, Cameron D. Yang, Gary CA NCCN Gastric Canc Panel Members TI Gastric Cancer Clinical Practice Guidelines in Oncology (TM) SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; gastric carcinoma; chemoradiation; combined modality therapy; chemotherapy; surgery; resection (JNCCN 2010;8:378-409) ID MULTICENTER PHASE-II; ADVANCED ESOPHAGOGASTRIC CANCER; GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA; ENDOSCOPIC MUCOSAL RESECTION; POSITRON-EMISSION-TOMOGRAPHY; LYMPH-NODE DISSECTION; S-1 PLUS CISPLATIN; MALIGNANT GASTRODUODENAL OBSTRUCTION; UPPER GASTROINTESTINAL MALIGNANCIES; PROSPECTIVE RANDOMIZED TRIAL C1 [Ajani, Jaffer A.; Das, Prajnan; Hofstetter, Wayne L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Barthel, James S.; Meredith, Kenneth] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Bekaii-Saab, Tanios] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bentrem, David J.; Keswani, Rajesh N.; Mulcahy, Mary F.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Denlinger, Crystal; Scott, Walter J.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Fuchs, Charles S.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Gerdes, Hans; Ilson, David H.; Strong, Vivian E. M.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Hayman, James A.; Orringer, Mark B.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Hazard, Lisa] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Kleinberg, Lawrence R.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Korn, Michael] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Osarogiagbon, Raymond U.] Univ Tennessee, Inst Canc, Knoxville, TN 37996 USA. [Posey, James A.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Sasson, Aaron R.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Shibata, Stephen] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Washington, Mary Kay] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Wood, Douglas E.] Univ Washington, Seattle, WA 98195 USA. [Wright, Cameron D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Yang, Gary] Roswell Pk Canc Inst, Buffalo, NY USA. [Osarogiagbon, Raymond U.] St Jude Childrens Res Hosp, Memphis, TN USA. [Wood, Douglas E.] Seattle Canc Care Alliance, Seattle, WA USA. RP Ajani, JA (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Bekaii-Saab, Tanios/E-2733-2011 NR 161 TC 78 Z9 87 U1 0 U2 9 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2010 VL 8 IS 4 BP 378 EP 409 PG 32 WC Oncology SC Oncology GA 615ZL UT WOS:000279177200003 PM 20410333 ER PT J AU Holland, JC Andersen, B Breitbart, WS Compas, B Dudley, MM Fleishman, S Fulcher, CD Greenberg, DB Greiner, CB Handzo, GF Hoofring, L Jacobsen, PB Knight, SJ Learson, K Levy, MH Loscalzo, MJ Manne, S McAllister-Black, R Riba, MB Roper, K Valentine, AD Wagner, LI Zevon, MA AF Holland, Jimmie C. Andersen, Barbara Breitbart, William S. Compas, Bruce Dudley, Moreen M. Fleishman, Stewart Fulcher, Caryl D. Greenberg, Donna B. Greiner, Carl B. Handzo, George F. Hoofring, Laura Jacobsen, Paul B. Knight, Sara J. Learson, Kate Levy, Michael H. Loscalzo, Matthew J. Manne, Sharon McAllister-Black, Randi Riba, Michelle B. Roper, Kristin Valentine, Alan D. Wagner, Lynne I. Zevon, Michael A. CA NCCN Distress Management Panel Mem TI Distress Management Clinical Practice Guidelines in Oncology (TM) SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; psychosocial; psychological; psychiatric; distress; anxiety; depression; quality of life ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; MARROW TRANSPLANT PATIENTS; PRIMARY BREAST-CANCER; BRAIN-TUMOR PATIENTS; PSYCHOLOGICAL DISTRESS; COGNITIVE FUNCTION; PSYCHOSOCIAL INTERVENTIONS; PSYCHIATRIC-DISORDERS; PALLIATIVE CARE C1 [Holland, Jimmie C.; Breitbart, William S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Andersen, Barbara] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Compas, Bruce] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Dudley, Moreen M.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Dudley, Moreen M.] Seattle Canc Care Alliance, Seattle, WA USA. [Fulcher, Caryl D.] Duke Comprehens Canc Ctr, Durham, NC USA. [Greenberg, Donna B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Greiner, Carl B.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Hoofring, Laura] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Jacobsen, Paul B.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Knight, Sara J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Levy, Michael H.; Manne, Sharon] Fox Chase Canc Ctr, Philadelphia, PA USA. [Loscalzo, Matthew J.; McAllister-Black, Randi] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Riba, Michelle B.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Roper, Kristin] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Valentine, Alan D.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Wagner, Lynne I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Zevon, Michael A.] Roswell Pk Canc Inst, Buffalo, NY USA. RP Holland, JC (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 83 TC 61 Z9 66 U1 1 U2 12 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2010 VL 8 IS 4 BP 448 EP 485 PG 38 WC Oncology SC Oncology GA 615ZL UT WOS:000279177200007 PM 20410337 ER PT J AU Jaja, C Pares-Avila, J Wolpin, S Berry, D AF Jaja, Cheedy Pares-Avila, Jose Wolpin, Seth Berry, Donna TI Usability Evaluation of the Interactive Personal Patient Profile-Prostate Decision Support System With African American Men SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE prostate cancer; knowledge, attitudes, and beliefs; African Americans; men's health ID CANCER; MORTALITY; PROGRAM; ALOUD AB Background: The Personal Patient Profile-Prostate (P4) program is an interactive Web-based decision support system that provides men with localized prostate cancer customized education and coaching with which to make the best personal treatment decision. This study assessed functionality and usability of the P4 program and identified problems in user-computer interaction in a sample of African American men. Methods: Usability testing was conducted with 12 community-dwelling African American adult men. The health status of participants was not known or collected by the research team. Each participant worked with the P4 program and provided simultaneous feedback using the "think aloud" technique. Handwritten field notes were collated and assigned to 3 standard coded categories. Aspects of P4 program usability was made based on common issues in the assigned categories. Summary statistics were derived for types and frequency of usability issues noted in the coded data. Results: Twelve participants reported a total of 122 usability comments, with a mean of 9 usability comments. The most common usability issue by participant was completeness of information content, which comprised 53 (43%) of the total issues. Comprehensibility of text and graphics was second, comprising 51(42%) of the total issues. Conclusion: This study provided initial inventory of usability issues for community African American men that may potentially interfere with application of the P4 system in the community setting and overall system usability, confirming the need for usability testing of a culturally appropriate Internet-based decision support system before community application. C1 [Jaja, Cheedy] Med Coll Georgia, Sch Nursing Hlth Environm & Syst, Augusta, GA 30912 USA. [Pares-Avila, Jose] Community Hlth Assoc Spokane, Denny Murphy Clin, Spokane, WA USA. [Wolpin, Seth] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Berry, Donna] Phyllis F Cantor Ctr Res Nursing & Patient Care S, Dana Farber Canc Inst, Boston, MA USA. RP Jaja, C (reprint author), Med Coll Georgia, Sch Nursing, Augusta, GA 30912 USA. EM cjaja@mcg.edu RI Pares, Albert/G-1328-2011 OI Pares, Albert/0000-0002-5413-9687 FU National Institutes of Health [R01 NR009692] FX This research was supported by the National Institutes of Health (R01 NR009692). NR 33 TC 5 Z9 6 U1 2 U2 3 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD APR PY 2010 VL 102 IS 4 BP 290 EP 297 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 586OA UT WOS:000276918700002 PM 20437736 ER PT J AU Shah, SA Spinale, FG Ikonomidis, JS Stroud, RE Chang, EI Reed, CE AF Shah, Sonam A. Spinale, Francis G. Ikonomidis, John S. Stroud, Robert E. Chang, Eileen I. Reed, Carolyn E. TI Differential matrix metalloproteinase levels in adenocarcinoma and squamous cell carcinoma of the lung SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 09-13, 2009 CL Boston, MA SP Amer Assoc Thorac Surg ID CANCER PATIENTS; TISSUE INHIBITOR; PLASMA MATRIX-METALLOPROTEINASE-9; VENTRICULAR MYOCARDIUM; COLORECTAL-CANCER; MESSENGER-RNA; PHASE-III; EXPRESSION; PROGNOSIS; SURVIVAL AB Objective: The matrix metalloproteinases (MMPs) have been implicated in the aggressive course of non-small cell lung cancer (NSCLC). However, there are a large number of MMP subtypes with diverse proteolytic substrates and different induction pathways. This study tested the hypothesis that a differential MMP profile would exist between NSCLC and normal lung and that MMP patterns would differ between NSCLC histologic types. Methods: NSCLC samples and remote normal samples were obtained from patients with stage I or II NSCLC with either squamous cell (n = 22) or adenocarcinoma (n = 19) histologic characteristics. Absolute concentrations for each of the MMP subclasses were determined by a calibrated and validated multiplex suspension array: collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), lysins (MMP-2 and -7), and elastase (MMP-12). Results: Overall, MMP levels were significantly increased in NSCLC compared with normal. For example, MMP-1 and MMP-7 increased by approximately 10-fold in NSCLC (P < .05). Moreover, a different MMP portfolio was observed between NSCLC histologic types. For example MMP-1, -8, -9, and -12 increased by more than 4-fold in squamous cell versus adenocarcinoma (P < .05). In those patients who had recurrence within 3 years of resection, 3-fold higher levels of MMP-8 and -9 were observed (P < .05). Conclusion: Increased levels of a number of MMP types occur with NSCLC, but the MMP profile was distinctly different between histologic types and in those patients with recurrence. These different MMP profiles may be important in the mechanistic basis for the natural history of different NSCLC types, as well as identifying potential prognostic and therapeutic targets. (J Thorac Cardiovasc Surg 2010; 139: 984-90) C1 [Reed, Carolyn E.] MUSC, Dept Surg, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Reed, CE (reprint author), MUSC, Dept Surg, Div Cardiothorac Surg, 25 Courtenay Dr, Charleston, SC 29425 USA. EM reedce@musc.edu OI Chang, Eileen/0000-0002-3444-7260 FU NHLBI NIH HHS [R01 HL059165, HL59165, HL81691, R01 HL059165-11] NR 39 TC 13 Z9 13 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 2010 VL 139 IS 4 BP 984 EP 990 DI 10.1016/j.jtcvs.2009.12.016 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 572GG UT WOS:000275815000025 PM 20304142 ER PT J AU Evans, NR Li, S Wright, CD Allen, MS Gaissert, HA AF Evans, Nathaniel R., III Li, Shuang Wright, Cameron D. Allen, Mark S. Gaissert, Henning A. TI The impact of induction therapy on morbidity and operative mortality after resection of primary lung cancer SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Western-Thoracic-Surgical-Association CY JUN 24-27, 2009 CL Banff, CANADA SP Western Thorac Surg Assoc ID THORACIC-SURGERY DATABASE; NEOADJUVANT THERAPY; CHEMOTHERAPY; COMPLICATIONS; SOCIETY; TRIAL; RISKS AB Objective: Use and operative results of neoadjuvant therapy before major elective resection for primary lung cancer were examined in the Society of Thoracic Surgeons General Thoracic Surgical Database. Methods: Lobectomy and pneumonectomy for primary lung cancer were identified in 12,201 patients between January 2002 and June 2008. After excluding procedures for missing clinical staging or end points; institutions with more than 10% missing data for clinical stage, discharge mortality, or length of stay; and patients treated with chemotherapy or radiation for unrelated disease, there remained 5376 resections. Study end points were discharge mortality, length of stay more than 14 days, and major morbidity. Multivariate analysis using propensity scores stratified into quintiles measured the effect of induction therapy. Results: In 525 of 5376 procedures (9.8%), chemotherapy (n = 153), radiotherapy (23), or chemoradiotherapy (349) preceded resection. Compared with resection only, patients receiving induction therapy were younger and had fewer comorbidities, more reoperative surgery, and higher rates of pneumonectomy. Clinical IIIA-N2 disease was treated with induction therapy in only 203 of 397 patients (51.1%). Propensity-adjusted rates detected no difference in discharge mortality, prolonged length of stay, or a composite of major morbidity for patients receiving induction therapy. Similar results were obtained in a logistic regression model (discharge mortality P = 9883; prolonged hospital stay P = .9710; major morbidity P = .9678). Conclusion: Less than 10% of all major lung resections for primary carcinoma and just more than half of all resections for clinical stage IIIA-N2 disease are preceded by neoadjuvant chemotherapy or radiation. This study does not support concerns over excessive operative risk of induction therapy. (J Thorac Cardiovasc Surg 2010;139:991-6) C1 [Evans, Nathaniel R., III; Wright, Cameron D.; Gaissert, Henning A.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Li, Shuang] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Allen, Mark S.] Mayo Clin, Div Thorac Surg, Rochester, MN USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org RI Evans, Nathaniel/I-2255-2013 OI Evans, Nathaniel/0000-0001-5767-6907 NR 15 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 2010 VL 139 IS 4 BP 991 EP U36 DI 10.1016/j.jtcvs.2009.11.070 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 572GG UT WOS:000275815000026 PM 20304144 ER PT J AU Zhou, J Shi, J Hou, J Cao, F Zhang, Y Rasmussen, JT Heegaard, CW Gilbert, GE AF Zhou, J. Shi, J. Hou, J. Cao, F. Zhang, Y. Rasmussen, J. T. Heegaard, C. W. Gilbert, G. E. TI Phosphatidylserine exposure and procoagulant activity in acute promyelocytic leukemia SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE differentiation; factor Xase; lactadherin; mfg-e8; prothrombinase; tissue factor ID TISSUE FACTOR; RETINOIC ACID; CANCER PROCOAGULANT; ENZYME COMPLEXES; CELL-LINE; LACTADHERIN; BINDING; TRANSLOCATION; COAGULATION; HEMOSTASIS AB Background: Acute promyelocytic leukemia (APL) frequently causes disseminated intravascular coagulation that can worsen with cytotoxic chemotherapy but improve with the therapeutic differentiating agents, all trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)). APL cells display tissue factor but the relationship of tissue factor and other procoagulant activity to phosphatidylserine (PS) exposure is largely unknown. Methods: Lactadherin, a milk protein with stereospecific binding to phosphatidyl-L-serine, was used as a probe for PS exposure on an immortalized APL cell line (NB4) and on the cells of eight patients with APL. PS exposure was evaluated with flow cytometry, confocal microscopy, coagulation assays, and purified prothrombinase and factor (F) Xase assays. Results: Plasma procoagulant activity of NB4 and APL cells increased approximately 15-fold after exposure to etoposide or daunorubicin and decreased 80% after treatment with ATRA or As(2)O(3). Procoagulant activity corresponded to exposed PS on viable APL cells. PS exposure decreased after treatment with ATRA or As(2)O(3) and increased after treatment with daunorubicin or etoposide. Excess lactadherin inhibited 80-85% of intrinsic FXase, FVIIa-tissue factor and prothrombinase activities on both NB4 cells and APL cells. Confocal microscopy identified membrane patches that stained with lactadherin, but not annexin V, demonstrating focal, low-level PS exposure. Conclusions: PS is exposed on viable APL cells and is necessary for approximately 80% of procoagulant activity. C1 [Shi, J.; Gilbert, G. E.] Brigham & Womens Hosp, Dept Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Zhou, J.; Shi, J.; Hou, J.; Cao, F.; Zhang, Y.] Harbin Med Coll, Affiliated Hosp 1, Dept Hematol, Harbin, Peoples R China. [Rasmussen, J. T.; Heegaard, C. W.] Univ Aarhus, Dept Mol Biol, Prot Chem Lab, Aarhus C, Denmark. RP Gilbert, GE (reprint author), VA Boston Healthcare Ctr, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM jinzhouh85@163.com; ggilbert@rics.bwh.harvard.edu FU National Natural Science Foundation of China [30871227]; Scientific Foundation of Heilongjiang Province [GB08C401-02]; Scientific Research Fund of Heilongjiang Provincial Education Department [11531207]; Department of Veterans Affairs Merit Grant FX This research was supported by grants from the National Natural Science Foundation of China (30871227), Scientific Foundation of Heilongjiang Province (GB08C401-02), Scientific Research Fund of Heilongjiang Provincial Education Department (11531207), and a Department of Veterans Affairs Merit Grant to G. E. Gilbert. NR 33 TC 24 Z9 27 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD APR PY 2010 VL 8 IS 4 BP 773 EP 782 DI 10.1111/j.1538-7836.2010.03763.x PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 573OE UT WOS:000275922500023 PM 20102487 ER PT J AU Lipinski, B AF Lipinski, Boguslaw TI Modification of fibrin structure as a possible cause of thrombolytic resistance SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Free radicals; Fibrin(ogen); Proteolysis; Chelating agents; Free radical scavengers ID LABILE IRON POOL; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; IN-VITRO; DEGRADATION; PLASMA; POLYMERIZATION; PURIFICATION; CHELATION; PRODUCTS AB This paper presents a concept according to which free radicals, specifically the most biologically active hydroxyl radicals, induce structural modifications in fibrin(ogen) molecules making them resistant to proteolytic degradation. Such changes are analogous to those in congeneticaly altered fibrinogen that give rise to plasmin resistant fibrin clots and consequently to thrombosis. In view of the fact that hydroxyl radicals are generated in the Fenton reaction in the presence of iron and/or copper ions, the use of chelating agents to facilitate thrombolysis is rationalized. Moreover, the resistance of thrombi older than 3 h to proteolytic degradation may be abrogated by the administration of free radical scavengers, particularly those that can be neutralized by virtue of aromatic hydroxylation, such as salicylates and polyphenolic compounds. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Genet & Epidemiol, Boston, MA 02215 USA. RP Lipinski, B (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Genet & Epidemiol, Boston, MA 02215 USA. EM boguslaw_lipinski@joslin.harvard.edu NR 32 TC 15 Z9 15 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD APR PY 2010 VL 29 IS 3 BP 296 EP 298 DI 10.1007/s11239-009-0367-6 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 568WI UT WOS:000275555100006 PM 19551349 ER PT J AU Alam, HB AF Alam, Hasan B. TI Beneficial Effects of Activation of PKC on Hemorrhagic Shock in Rats COMMENT SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Editorial Material ID FLUID RESUSCITATION; TRAUMA C1 Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Alam, HB (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD APR PY 2010 VL 68 IS 4 BP 873 EP 873 PG 1 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 583GY UT WOS:000276663100022 ER PT J AU Eisner, BH Porten, SP Bechis, SK Stoller, ML AF Eisner, Brian H. Porten, Sima P. Bechis, Seth K. Stoller, Marshall L. TI The Role of Race in Determining 24-Hour Urine Composition in White and Asian/Pacific Islander Stone Formers SO JOURNAL OF UROLOGY LA English DT Article DE urinary calculi; urine; Oceanic ancestry group; European continental ancestry group; Asian continental ancestry group ID IDIOPATHIC CALCIUM NEPHROLITHIASIS; RISK; HYPERTENSION; WOMEN AB Purpose: We examined differences in 24-hour urine composition between white and Asian/Pacific Islander stone formers. Materials and Methods: We retrospectively reviewed the 24-hour urinalysis database at a metabolic stone clinic. We identified and included in the study patients 18 years old or older who presented for the initial metabolic stone evaluation when race was marked as white or Asian/Pacific Islander in the electronic medical record. Univariate analysis was done to compare 24-hour urine composition between white and Asian/Pacific Islander stone formers. We performed multivariate linear regression adjusted for possible confounders, including age, gender, body mass index, hypertension, diabetes mellitus, thiazide use, potassium citrate use and 24-hour urine chemistry (volume, pH, calcium, citrate, creatinine, oxalate, magnesium, phosphate, potassium, sodium, sulfate and uric acid). Results: Included in analysis were 371 white and 91 Asian/Pacific Islander patients. On univariate analysis Asian/Pacific Islander patients excreted significantly greater uric acid, and significantly less citrate, magnesium, phosphate and creatinine than white patients. On multivariate analysis Asian/Pacific Islander patients excreted significantly greater uric acid, and significantly less urine citrate, phosphate, creatinine and volume than white patients. Conclusions: Significant differences exist in 24-hour urine chemistry between white and Asian/PI stone formers. Knowledge of these differences would be useful to evaluate and treat these patients, and prevent stone recurrence. C1 [Eisner, Brian H.; Porten, Sima P.; Bechis, Seth K.; Stoller, Marshall L.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Eisner, BH (reprint author), Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 20 TC 10 Z9 10 U1 0 U2 3 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 APR PY 2010 VL 183 IS 4 BP 1407 EP 1411 DI 10.1016/j.juro.2009.12.033 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 574DG UT WOS:000275968200056 PM 20171692 ER PT J AU Wallace, MJ Chin, KW Fletcher, TB Bakal, CW Cardella, JF Grassi, CJ Grizzard, JD Kaye, AD Kushner, DC Larson, PA Liebscher, LA Luers, PR Mauro, MA Kundu, S AF Wallace, Michael J. Chin, Kenneth W. Fletcher, Thomas B. Bakal, Curtis W. Cardella, John F. Grassi, Clement J. Grizzard, John D. Kaye, Alan D. Kushner, David C. Larson, Paul A. Liebscher, Lawrence A. Luers, Patrick R. Mauro, Matthew A. Kundu, Sanjoy TI Quality Improvement Guidelines for Percutaneous Drainage/Aspiration of Abscess and Fluid Collections SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID CT-GUIDED DRAINAGE; CATHETER DRAINAGE; NEEDLE ASPIRATION; PELVIC ABSCESSES; THERAPEUTIC MANAGEMENT; LIVER; GUIDANCE; DISEASE C1 [Wallace, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Chin, Kenneth W.] Univ Calif Los Angeles, Med Ctr, Dept Radiol, Los Angeles, CA 90024 USA. [Fletcher, Thomas B.] Austin Radiol Associates, Austin, TX USA. [Bakal, Curtis W.] Lahey Clin Fdn, Dept Vasc & Intervent Radiol, Burlington, MA USA. [Cardella, John F.] Geisinger Hlth Syst, Dept Radiol, Danville, PA USA. [Grassi, Clement J.] Vet Affairs Med Ctr, Boston Healthcare Syst, Dept Radiol, Boston, MA USA. [Grizzard, John D.] Virginia Commonwealth Univ, Dept Radiol, Richmond, VA USA. [Kaye, Alan D.] Bridgeport Hosp, Dept Radiol, Bridgeport, CT USA. [Kushner, David C.] Eastern Virginia Med Sch, Childrens Hosp Kings Daughters, Dept Radiol, Norfolk, VA 23501 USA. [Larson, Paul A.] Radiol Associates Fox Valley, Neenah, WI USA. [Liebscher, Lawrence A.] Waverly Municipal Hosp, Dept Radiol, Waverly, IA USA. [Luers, Patrick R.] Mt Med Phys Specialists, Salt Lake City, UT USA. [Mauro, Matthew A.] Univ N Carolina Hosp, Dept Radiol, Chapel Hill, NC USA. [Kundu, Sanjoy] Vein Inst Toronto, Toronto, ON, Canada. RP Wallace, MJ (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, 1515 Holcombe Blvd,Box 325, Houston, TX 77030 USA. EM mwallace@di.mdacc.tmu.edu FU Siemens Medical Systems (Iselin, New Jersey) FX M.J.W. has research funded wholly or in part by Siemens Medical Systems (Iselin, New Jersey). None of the other authors have identified a conflict of interest. NR 28 TC 13 Z9 13 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2010 VL 21 IS 4 BP 431 EP 435 DI 10.1016/j.jvir.2009.12.398 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 583HE UT WOS:000276663700002 PM 20346880 ER PT J AU Raffetto, JD Qiao, XY Beauregard, KG Tanbe, AF Kumar, A Mam, V Khalil, RA AF Raffetto, Joseph D. Qiao, Xiaoying Beauregard, Katie G. Tanbe, Alain F. Kumar, Abhinav Mam, Virak Khalil, Raouf A. TI Functional adaptation of venous smooth muscle response to vasoconstriction in proximal, distal, and varix segments of varicose veins SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ANGIOTENSIN-II; VASOACTIVE AGENTS; SAPHENOUS VEINS; CALCIUM INFLUX; MECHANISMS; RECEPTOR; MATRIX; RATS; WALL; HYPERTENSION AB Background: Varicose veins (VarVs) are a common disorder of venous dilation and tortuosity with unclear mechanism. The functional integrity and the ability of various regions of the VarVs to constrict is unclear. This study tested the hypothesis that the different degrees of venodilation in different VarV regions reflect segmental differences in the responsiveness to receptor-dependent vasoconstrictive stimuli and/or in the postreceptor signaling mechanisms of vasoconstriction. Methods: Varix segments and adjacent proximal and distal segments were obtained from patients undergoing VarV stripping. Control great saphenous vein specimens were obtained from patients undergoing lower extremity arterial bypass and coronary artery bypass grafting. Circular vein segments were equilibrated under 2 g of tension in a tissue bath, and changes in isometric constriction in response to angiotensin II (AngII, 10(-11) phenylephrine (PHE, 10(-9)-10(-4) M), and KCl (96 mM) were recorded. The amount of angiotensin type 1 receptor (ATER) was measured in vein tissue homogenate. Results: AngII caused concentration-dependent constriction in control vein (max 35.3 +/- 9.6 mg/mg tissue, pED(50) 8.48 +/- 0.34). AngII caused less contraction and was less potent in proximal (max 7.9 +/- 2.5, pED(50) 6.85 +/- 0.61), distal (max 5.7 +/- 1.2, pED(50) 6.74 +/- 0.68), and varix segments of VarV (max 7.2 +/- 2.0, pED(50) 7.11 +/- 0.50), suggesting reduced ATER-mediated contractile mechanisms. VarVs and control veins had similar amounts of ATER. a-adrenergic receptor stimulation with PHE caused concentration-dependent constriction in control veins (max 73.0 +/- 13.9 mg/mg tissue, pED(50) 5.48 +/- 0.12) exceeding that of AngII. PHE produced similar constriction and was equally potent in varix and distal segments but produced less constriction and was less potent in proximal segments of VarVs (max 32.1 +/- 6.4 mg/mg tissue, pED(50) 4.89 +/- 0.13) vs control veins. Membrane depolarization by 96 mM KCl, a receptor-independent Ca(2+)-dependent response, produced significant constriction in control veins and similar contractile response in proximal, distal, and varix VarV segments, indicating tissue viability and intact Ca(2+)-dependent contraction mechanisms. Conclusions: Compared with control veins, different regions of VarV display reduced AngII-mediated venoconstriction, which may be involved in the progressive dilation in VarVs. Postreceptor Ca(2+)-dependent contraction mechanisms remain functional in VarVs. The maintained a-adrenergic responses in distal and varix segments, and the reduced constriction in the upstream proximal segments, may represent a compensatory adaptation of human venous smooth muscle to facilitate venous return from the dilated varix segments of VarV.(J Vase Surg 2010;51:962-71.) C1 [Raffetto, Joseph D.; Qiao, Xiaoying; Beauregard, Katie G.; Tanbe, Alain F.; Kumar, Abhinav; Mam, Virak; Khalil, Raouf A.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Raffetto, Joseph D.] VA Boston Healthcare Syst, W Roxbury, MA USA. [Raffetto, Joseph D.; Khalil, Raouf A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Khalil, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Vasc Surg, 75 Francis St, Boston, MA 02115 USA. EM raouf_khalil@hms.harvard.edu FU National Heart, Lung, and Blood Institute [HL-65998, HL-70659]; Eunice Kennedy Shover National Institute of Child Health and Human Development [HD-60702] FX This work was supported by grants from National Heart, Lung, and Blood Institute (HL-65998 and HL-70659) and The Eunice Kennedy Shover National Institute of Child Health and Human Development (HD-60702). NR 30 TC 4 Z9 4 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 2010 VL 51 IS 4 BP 962 EP 971 DI 10.1016/j.jvs.2009.11.037 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 577JU UT WOS:000276220000023 PM 20347695 ER PT J AU Raffetto, JD Qiao, XY Beauregard, KG Khalil, RA AF Raffetto, Joseph D. Qiao, Xiaoying Beauregard, Katie G. Khalil, Raouf A. TI Estrogen receptor-mediated enhancement of venous relaxation in female rat: Implications in sex-related differences in varicose veins SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID VASCULAR SMOOTH-MUSCLE; CA2+ ENTRY MECHANISMS; GENDER-DIFFERENCES; RISK-FACTORS; CORONARY-ARTERIES; HYPERTENSIVE-RATS; SAPHENOUS VEINS; ALPHA; BETA; 17-BETA-ESTRADIOL AB Background: A greater incidence of varicose veins has been reported in premenopausal women than in men. We hypothesized that the sex differences in venous function reflect reduced constriction and enhanced venous dilation in women due to direct venous relaxation effects of estrogen on specific estrogen receptors (ER). Methods: Circular segments of inferior vena cava (IVC) from male and female Sprague-Dawley rats were suspended between two wires, and isometric contraction (in mg/mg tissue) to phenylephrine, angiotensin II (AngII), and 96 mM KCl was measured. To investigate sex differences in venous smooth muscle, Ca(2+) release from the intracellular stores, and Ca(2+) entry from the extracellular space, the transient phenylephrine contraction in 0 Ca(2+) Krebs was measured. Extracellular CaCl(2) (0.1, 0.3, 0.6, 1, 2.5 mM) was added, and the [Ca(2+)](c)-dependent contraction was measured. To investigate sex differences in venous endothelial function, acetylcholine-induced relaxation was measured. To test the role of specific ERs, the amount of venous tissue ERs was measured using Western blots, and the venous relaxation in response to 17 beta-estradiol (E2, activator of most ERs), 4,4,'4 ''-propy[1H]-pyrazole-1,3,5-triy1)-tris-Phenol (PPT; ER alpha agonist), 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; ER beta agonist), and ICI 182,780 (ERa/ERI3 antagonist, and G protein-coupled receptor 30 [GPR30] agonist) was measured in IVC segments nontreated or treated with the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). Results:Phenylephrine caused concentration-dependent contraction that was less in female (max 104.2 +/- 16.2) than male WC (172.4 +/- 20.4). AngII (10(-6))-induced contraction was also less in female (81.0 +/- 11.1) than male IVC (122.5 +/- 15.0). Phenylephrine contraction in 0 Ca2+ Krebs was insignificantly less in female (4.8 +/- 1.8) than male IVC (7.2 +/- 1.7), suggesting little difference in the intracellular Ca(2+) release mechanism. In contrast, the [Ca(2+)](c)-dependent contraction was significantly reduced in female than male IVC. Also, contraction to membrane depolarization by 96 mM KCl, which stimulates Ca2+ influx, was less in female (129.7 +/- 16.7) than male IVC (319.7 +/- 30.4), supporting sex differences in Ca2+ entry. Acetylcholine relaxation was greater in female (max 80.6% +/- 4.1%) than male IVC (max 48.0% +/- 6.1%), suggesting sex differences in the endothelium-dependent relaxation pathway. Western blots revealed greater amounts of ERa, ER beta, and GPR30 in female than male IVC. ER agonists caused concentration-dependent relaxation of phenylcphrine contraction in female WC. E2-induced relaxation (max 76.5% +/- 3.4%) was more than DPN (74.8% +/- 9.1%), PPT (71.4% +/- 12.5%), and ICI 182,780(67.4% +/- 7.8%), and was similar in L-NAME-treated and nontreated IVC. Conclusion: The reduced alpha-adrcnergic, AngII, depolarization-induced, and [Ca(2+)](c)-dependent venous contraction in female rats is consistent with sex differences in the Ca(2+) entry mechanisms, possibly due to enhanced endothelium-dependent vasodilation and increased ER expression/activity in female rats. E2/ER-mediated venous relaxation in female rats is not prevented by NOS blockade, suggesting activation of an NO-independent relaxation pathway. The decreased venous contraction and enhanced E2/ER-mediated venous relaxation would lead to more distensible veins in female rats. (J Vase Surg 2010;51:972-81.) C1 [Raffetto, Joseph D.; Qiao, Xiaoying; Beauregard, Katie G.; Khalil, Raouf A.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Raffetto, Joseph D.; Khalil, Raouf A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Raffetto, Joseph D.] VA Boston Healthcare Syst, W Roxbury, MA USA. RP Khalil, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Vasc Surg, 75 Francis St, Boston, MA 02115 USA. EM raouf_khalil@hms.harvard.edu FU National Heart, Lung, and Blood Institute [HL-65998, HL-70659]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD-60702] FX This work was supported by grants from National Heart, Lung, and Blood Institute (HL-65998 and HL-70659) and The Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-60702). NR 53 TC 17 Z9 18 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 2010 VL 51 IS 4 BP 972 EP 981 DI 10.1016/j.jvs.2009.11.074 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 577JU UT WOS:000276220000024 PM 20347696 ER PT J AU Xiang, SH Finzi, A Pacheco, B Alexander, K Yuan, W Rizzuto, C Huang, CC Kwong, PD Sodroski, J AF Xiang, Shi-Hua Finzi, Andres Pacheco, Beatriz Alexander, Kevin Yuan, Wen Rizzuto, Carlo Huang, Chih-Chin Kwong, Peter D. Sodroski, Joseph TI A V3 Loop-Dependent gp120 Element Disrupted by CD4 Binding Stabilizes the Human Immunodeficiency Virus Envelope Glycoprotein Trimer SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 GP120; TYPE-1 GP120; CELL-LINE; MONOCLONAL-ANTIBODIES; CHEMOKINE RECEPTORS; SOLUBLE CD4; N-TERMINUS; NEUTRALIZATION SENSITIVITY; MOLECULAR CHARACTERIZATION; DISTINCT CONFORMATIONS AB Human immunodeficiency virus (HIV-1) entry into cells is mediated by a trimeric complex consisting of noncovalently associated gp120 (exterior) and gp41 (transmembrane) envelope glycoproteins. The binding of gp120 to receptors on the target cell alters the gp120-gp41 relationship and activates the membrane-fusing capacity of gp41. Interaction of gp120 with the primary receptor, CD4, results in the exposure of the gp120 third variable (V3) loop, which contributes to binding the CCR5 or CXCR4 chemokine receptors. We show here that insertions in the V3 stem or polar substitutions in a conserved hydrophobic patch near the V3 tip result in decreased gp120-gp41 association (in the unliganded state) and decreased chemokine receptor binding (in the CD4-bound state). Subunit association and syncytium-forming ability of the envelope glycoproteins from primary HIV-1 isolates were disrupted more by V3 changes than those of laboratory-adapted HIV-1 envelope glycoproteins. Changes in the gp120 beta 2, beta 19, beta 20, and beta 21 strands, which evidence suggests are proximal to the V3 loop in unliganded gp120, also resulted in decreased gp120-gp41 association. Thus, a gp120 element composed of the V3 loop and adjacent beta strands contributes to quaternary interactions that stabilize the unliganded trimer. CD4 binding dismantles this element, altering the gp120-gp41 relationship and rendering the hydrophobic patch in the V3 tip available for chemokine receptor binding. C1 [Xiang, Shi-Hua; Finzi, Andres; Pacheco, Beatriz; Alexander, Kevin; Yuan, Wen; Rizzuto, Carlo; Sodroski, Joseph] Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med,Dept Pathol,Div AIDS, Boston, MA 02115 USA. [Huang, Chih-Chin; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med,Dept Pathol,Div AIDS, 44 Binney St,CLS 1010, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIH [AI24755, AI39420, AI40895]; Center for HIV/AIDS Vaccine Immunology [AI67854]; Center for AIDS Research [AI24848]; Bristol-Myers Squibb Foundation; International AIDS Vaccine Initiative FX We thank Yvette McLaughlin and Elizabeth Carpelan for manuscript preparation. We thank Michael Fung (Tanox) for the G3-299 antibody.; This study was supported by NIH grants AI24755, AI39420, and AI40895; by a Center for HIV/AIDS Vaccine Immunology grant (AI67854); by a Center for AIDS Research grant (AI24848); by an unrestricted research grant from the Bristol-Myers Squibb Foundation; by a gift from the late William F. McCarty-Cooper; and by funds from the International AIDS Vaccine Initiative. NR 88 TC 49 Z9 49 U1 0 U2 13 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 APR PY 2010 VL 84 IS 7 BP 3147 EP 3161 DI 10.1128/JVI.02587-09 PG 15 WC Virology SC Virology GA 565PV UT WOS:000275307400002 PM 20089638 ER PT J AU Pacheco, B Finzi, A McGee-Estrada, K Sodroski, J AF Pacheco, Beatriz Finzi, Andres McGee-Estrada, Kathleen Sodroski, Joseph TI Species-Specific Inhibition of Foamy Viruses from South American Monkeys by New World Monkey TRIM5 alpha Proteins SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS RESTRICTION; PRIMATE TRIM5-ALPHA; OLD-WORLD; INFECTION; DOMAIN; CELLS AB Foamy virus evolution closely parallels that of the host species, indicating virus-host coadaptation. We studied simian foamy viruses (SFVs) from common marmosets, spider monkeys, and squirrel monkeys, New World monkey (NWM) species that share geographic ranges. The TRIM5 alpha protein from each of these NWM species inhibited the replication of at least one of the SFVs associated with the other two species but did not affect the replication of its own SFV. Thus, TRIM5 alpha has potentially shaped the evolution of SFVs in NWM hosts. Conversely, SFVs may have influenced the evolution of TRIM5 variants in New World primates. C1 [Pacheco, Beatriz; Finzi, Andres; McGee-Estrada, Kathleen; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Pacheco, Beatriz; Finzi, Andres; McGee-Estrada, Kathleen; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,CLS 1010, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU National Institutes of Health [AI 063987, AI 076094, AI 06354]; International AIDS Vaccine Initiative; late William F. McCarty-Cooper FX This study was supported by the National Institutes of Health (grants AI 063987 and AI 076094 and Center for AIDS Research Award AI 06354), the International AIDS Vaccine Initiative, and the late William F. McCarty-Cooper. NR 23 TC 26 Z9 26 U1 0 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 APR PY 2010 VL 84 IS 8 BP 4095 EP 4099 DI 10.1128/JVI.02631-09 PG 5 WC Virology SC Virology GA 571UO UT WOS:000275781500035 PM 20130055 ER PT J AU Gold, KJ DeMonner, SM Lantz, PM Hayward, RA AF Gold, Katherine J. DeMonner, Sonya M. Lantz, Paula M. Hayward, Rodney A. TI Prematurity and Low Birth Weight as Potential Mediators of Higher Stillbirth Risk in Mixed Black/White Race Couples SO JOURNAL OF WOMENS HEALTH LA English DT Article ID FETAL-DEATH CERTIFICATES; UNITED-STATES; PERINATAL-MORTALITY; ETHNIC-DIFFERENCES; INFANT-MORTALITY; DISPARITY; VALIDITY; OUTCOMES; TRENDS AB Objective: Although births of multiracial and multiethnic infants are becoming more common in the United States, little is known about birth outcomes and risks for adverse events. We evaluated risk of fetal death for mixed race couples compared with same race couples and examined the role of prematurity and low birth weight as potential mediating risk factors. Methods: We performed a retrospective cohort analysis using data from the 1998-2002 California Birth Cohort to evaluate the odds of fetal death, low birth weight, and prematurity for couples with a mother and father who were categorized as either being of same or different racial groups. Risk of prematurity (birth prior to 37 weeks gestation) and low birth weight (<2500 g) were also tested to see if the model could explain variations among groups. Results: The analysis included approximately 1.6 million live births and 1749 stillbirths. In the unadjusted model, compared with two white parents, black/black and black/white couples had a significantly higher risk of fetal death. When all demographic, social, biological, genetic, congenital, and procedural risk factors except gestational age and birth weight were included, the odds ratios (OR) were all still significant. Black/black couples had the highest level of risk (OR 2.11, CI 1.77-2.51), followed by black mother/white father couples (OR 2.01, CI 1.16-3.48), and white mother/black father couples (OR 1.84, CI 1.33-2.54). Virtually all of the higher risk of fetal death was explainable by higher rates of low birth weight and prematurity. Conclusions: Mixed race black and white couples face higher odds of prematurity and low birth weight, which appear to contribute to the substantially higher demonstrated risk for stillbirth. There are likely additional unmeasured factors that influence birth outcomes for mixed race couples. C1 [Gold, Katherine J.] Univ Michigan, Dept Obstet & Gynecol, Dept Family Med, Ann Arbor, MI 48104 USA. [DeMonner, Sonya M.; Hayward, Rodney A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48104 USA. [DeMonner, Sonya M.; Hayward, Rodney A.] US Dept Vet Affairs, HSR&D Ctr Excellence, Ann Arbor, MI USA. [DeMonner, Sonya M.; Hayward, Rodney A.] Univ Michigan, Robert Wood Johnson Fdn Clin Scholars Program, Ann Arbor, MI 48104 USA. [Lantz, Paula M.; Hayward, Rodney A.] Univ Michigan, Sch Publ Hlth, Dept Hlth Management & Policy, Ann Arbor, MI 48104 USA. [Lantz, Paula M.] Univ Michigan, Inst Social Res, Ann Arbor, MI 48104 USA. RP Gold, KJ (reprint author), Univ Michigan, Dept Obstet & Gynecol, Dept Family Med, 1018 Fuller St, Ann Arbor, MI 48104 USA. EM ktgold@umich.edu FU Robert Wood Johnson Clinical Scholars Program FX Salary funding for K.J.G. and funding to purchase the original dataset were provided by the Robert Wood Johnson Clinical Scholars Program. NR 29 TC 10 Z9 10 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD APR PY 2010 VL 19 IS 4 BP 767 EP 773 DI 10.1089/jwh.2009.1561 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 587XS UT WOS:000277030400017 PM 20235877 ER PT J AU Conrad, P Carr, P Knight, S Renfrew, MR Dunn, MB Pololi, L AF Conrad, Peter Carr, Phyllis Knight, Sharon Renfrew, Megan R. Dunn, Mary B. Pololi, Linda TI Hierarchy as a Barrier to Advancement for Women in Academic Medicine SO JOURNAL OF WOMENS HEALTH LA English DT Article ID GENDER DISCRIMINATION; SEX; PROMOTION; FACULTY; INTERNISTS; WORKPLACE; COLLEGE; EQUITY; RACE AB Background: Research on barriers to professional advancement for women in academic medicine has not adequately considered the role of environmental factors and how the structure of organizations affects professional advancement and work experiences. This article examines the impact of the hierarchy, including both the organization's hierarchical structure and professionals' perceptions of this structure, in medical school organization on faculty members' experience and advancement in academic medicine. Methods: As part of an inductive qualitative study of faculty in five disparate U.S. medical schools, we interviewed 96 medical faculty at different career stages and in diverse specialties, using in-depth semistructured interviews, about their perceptions about and experiences in academic medicine. Data were coded and analysis was conducted in the grounded theory tradition. Results: Our respondents saw the hierarchy of chairs, based on the indeterminate tenure of department chairs, as a central characteristic of the structure of academic medicine. Many faculty saw this hierarchy as affecting inclusion, reducing transparency in decision making, and impeding advancement. Indeterminate chair terms lessen turnover and may create a bottleneck for advancement. Both men and women faculty perceived this hierarchy, but women saw it as more consequential. Conclusions: The hierarchical structure of academic medicine has a significant impact on faculty work experiences, including advancement, especially for women. We suggest that medical schools consider alternative models of leadership and managerial styles, including fixed terms for chairs with a greater emphasis on inclusion. This is a structural reform that could increase opportunities for advancement especially for women in academic medicine. C1 [Conrad, Peter] Brandeis Univ, Dept Sociol, Waltham, MA 02454 USA. [Carr, Phyllis] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Knight, Sharon] E Carolina Univ, Dept Hlth Educ & Promot, Coll Hlth & Human Performance, Greenville, NC USA. [Renfrew, Megan R.] Massachusetts Gen Hosp, Inst Hlth Policy, Dispar Solut Ctr, Boston, MA 02114 USA. [Dunn, Mary B.] Univ Texas Austin, Dept Management, McCombs Sch Business, Austin, TX 78712 USA. [Pololi, Linda] Brandeis Univ, Womens Studies Res Ctr, Waltham, MA 02454 USA. RP Conrad, P (reprint author), Brandeis Univ, Dept Sociol, 415 S St,Mailstop 071, Waltham, MA 02454 USA. EM conrad@brandeis.edu FU Josiah Macy, Jr. Foundation; Office of Public Health and Science, Office on Women's Health, and Office on Minority Health; National Institutes of Health, Office on Research on Women's Health; Agency for Healthcare Research and Quality; Centers of Disease Control and Prevention; Health Resources and Services Administration FX We gratefully acknowledge the critical funding support of the Josiah Macy, Jr. Foundation and the supplemental funds to support data analysis provided by Office of Public Health and Science, Office on Women's Health, and Office on Minority Health; National Institutes of Health, Office on Research on Women's Health; Agency for Healthcare Research and Quality; Centers of Disease Control and Prevention; and Health Resources and Services Administration. NR 30 TC 28 Z9 28 U1 1 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD APR PY 2010 VL 19 IS 4 BP 799 EP 805 DI 10.1089/jwh.2009.1591 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 587XS UT WOS:000277030400021 PM 20141385 ER PT J AU Brunelli, SM Chertow, GM Ankers, ED Lowrie, EG Thadhani, R AF Brunelli, Steven M. Chertow, Glenn M. Ankers, Elizabeth D. Lowrie, Edmund G. Thadhani, Ravi TI Shorter dialysis times are associated with higher mortality among incident hemodialysis patients SO KIDNEY INTERNATIONAL LA English DT Article DE adequacy; dialysis; epidemiology; mortality; outcome; session length ID NATIONAL COOPERATIVE DIALYSIS; MARGINAL STRUCTURAL MODELS; WEIGHT-GAIN; BODY-SIZE; SURVIVAL; RISK; ULTRAFILTRATION; CLEARANCE; TRIALS; COHORT AB There is an association between hemodialysis session length and mortality independent of the effects of session duration on urea clearance. However, previous studies did not consider changes in session length over time nor did they control for the influence of time-dependent confounding. Using data from a national cohort of 8552 incident patients on thrice-weekly, in-center hemodialysis, we applied marginal structural analysis to determine the association between session length and mortality. Exposure was based on prescribed session length with the outcome being death from any cause. On the 31st day after initiating dialysis, the patients were considered at-risk and remained so until death, censoring, or completion of 1 year on dialysis. On primary marginal structural analysis, session lengths <4h were associated with a 42% increase in mortality. Sensitivity analyses showed a dose-response relationship between session duration and mortality, and a consistency of findings across prespecified subgroups. Our study suggests that shorter hemodialysis sessions are associated with higher mortality when marginal structural analysis was used to adjust for time-dependent confounding. Further studies are needed to confirm these findings and determine causality. Kidney International (2010) 77, 630-636; doi: 10.1038/ki.2009.523; published online 20 January 2010 C1 [Brunelli, Steven M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Brunelli, Steven M.; Thadhani, Ravi] Harvard Univ, Sch Med, Boston, MA USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Ankers, Elizabeth D.; Thadhani, Ravi] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Brunelli, SM (reprint author), Brigham & Womens Hosp, Div Renal, 75 Francis St,MRB 4, Boston, MA 02115 USA. EM sbrunelli@partners.org FU NIH/NIDDK [DK079056, DK84974]; Genzyme FX This work was supported by awards from the NIH/NIDDK (DK079056 to SMB, DK84974 to RT). SMB has received consulting fees from C. B. Fleet Company; his spouse is employed by Genzyme. GMC serves on the Scientific Advisory Board for DaVita Clinical Research, receives research support from Amgen and has received research support and honoraria from Genzyme. NR 35 TC 38 Z9 38 U1 1 U2 2 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 APR PY 2010 VL 77 IS 7 BP 630 EP 636 DI 10.1038/ki.2009.523 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 569CJ UT WOS:000275573500011 PM 20090666 ER PT J AU Isakova, T Gutierrez, OM Wolf, M AF Isakova, Tamara Gutierrez, Orlando M. Wolf, Myles TI The hypothesis that bone turnover influences FGF23 secretion Reply SO KIDNEY INTERNATIONAL LA English DT Letter C1 [Gutierrez, Orlando M.; Wolf, Myles] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. [Isakova, Tamara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit,Dept Med, Boston, MA USA. RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, 1120 NW 14th St, Miami, FL 33136 USA. EM mwolf2@med.miami.edu NR 4 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 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2010 VL 77 IS 8 BP 743 EP 744 DI 10.1038/ki.2009.535 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 576MX UT WOS:000276149700014 ER PT J AU Li, YF Sheu, CC Ye, YQ de Andrade, M Wang, L Chang, SC Aubry, MC Aakre, JA Allen, MS Chen, F Cunningham, JM Deschamps, C Jiang, RX Lin, JE Marks, RS Pankratz, VS Su, L Li, Y Sun, ZF Tang, H Vasmatzis, G Harris, CC Spitz, MR Jen, J Wang, RY Zhang, ZF Christian, DC Wu, XF Yang, P AF Li, Yafei Sheu, Chau-Chyun Ye, Yuanqing de Andrade, Mariza Wang, Liang Chang, Shen-Chih Aubry, Marie C. Aakre, Jeremiah A. Allen, Mark S. Chen, Feng Cunningham, Julie M. Deschamps, Claude Jiang, Ruoxiang Lin, Jie Marks, Randolph S. Pankratz, V. Shane Su, Li Li, Yan Sun, Zhifu Tang, Hui Vasmatzis, George Harris, Curtis C. Spitz, Margaret R. Jen, Jin Wang, Renyi Zhang, Zuo-Feng Christian, David C. Wu, Xifeng Yang, Ping TI Genetic variants and risk of lung cancer in never smokers: a genome-wide association study SO LANCET ONCOLOGY LA English DT Article ID SUSCEPTIBILITY LOCUS; MULTIPLE-SCLEROSIS; SMOKING-CESSATION; CIGARETTE-SMOKING; TOBACCO-SMOKE; EXPRESSION; GLYPICANS; 5P15.33; ADENOCARCINOMA; AMPLIFICATION AB Background Lung cancer in individuals who have never smoked tobacco products is an increasing medical and public-health issue. We aimed to unravel the genetic basis of lung cancer in never smokers. Methods We did a four-stage investigation. First, a genome-wide association study of single nucleotide polymorphisms (SNPs) was done with 754 never smokers (377 matched case-control pairs at Mayo Clinic, Rochester, MN, USA). Second, the top candidate SNPs from the first study were validated in two independent studies among 735 (MD Anderson Cancer Center, Houston, TX, USA) and 253 (Harvard University, Boston, MA, USA) never smokers. Third, further replication of the top SNP was done in 530 never smokers (UCLA, Los Angeles, CA, USA). Fourth, expression quantitative trait loci (eQTL) and gene-expression differences were analysed to further elucidate the causal relation between the validated SNPs and the risk of lung cancer in never smokers. Findings 44 top candidate SNPs were identified that might alter the risk of lung cancer in never smokers. rs2352028 at chromosome 13q31.3 was subsequently replicated with an additive genetic model in the four independent studies, with a combined odds ratio of 1.46 (95% CI 1.26-1.70, p=5.94x10(-6)). A cis eQTL analysis showed there was a strong correlation between genotypes of the replicated SNPs and the transcription level of the gene GPC5 in normal lung tissues (p=1.96x10(-4)), with the high-risk allele linked with lower expression. Additionally, the transcription level of GPC5 in normal lung tissue was twice that detected in matched lung adenocarcinoma tissue (p=6.75x10(-11)). Interpretation Genetic variants at 13q31.3 alter the expression of GPC5, and are associated with susceptibility to lung cancer in never smokers. Downregulation of GPC5 might contribute to the development of lung cancer in never smokers. C1 [Li, Yafei; de Andrade, Mariza; Aakre, Jeremiah A.; Jiang, Ruoxiang; Pankratz, V. Shane; Li, Yan; Sun, Zhifu; Tang, Hui; Yang, Ping] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Wang, Liang; Aubry, Marie C.; Cunningham, Julie M.; Vasmatzis, George] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Allen, Mark S.; Deschamps, Claude] Mayo Clin, Coll Med, Dept Surg, Rochester, MN 55905 USA. [Marks, Randolph S.] Mayo Clin, Coll Med, Div Med Oncol, Rochester, MN 55905 USA. [Jen, Jin] Mayo Clin, Coll Med, Dept Pulm & Crit Care Med, Rochester, MN 55905 USA. [Sheu, Chau-Chyun; Chen, Feng; Su, Li; Christian, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Ye, Yuanqing; Lin, Jie; Spitz, Margaret R.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Chang, Shen-Chih; Wang, Renyi; Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Chang, Shen-Chih; Wang, Renyi; Zhang, Zuo-Feng] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Christian, David C.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Christian, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Yang, P (reprint author), Mayo Clin, Coll Med, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA. EM yang.ping@mayo.edu RI Tang, Hui/B-3643-2010; OI Sun, Zhifu/0000-0001-8461-7523 FU US National Institutes of Health [R01-CA80127, R01-CA84354, CA111646, CA127615, CA055769, CA092824, CA074386, CA090578, P50 CA90833, T32 CA09142]; Mayo Foundation FX Funding US National Institutes of Health; Mayo Foundation.; We thank Susan Ernst for her technical assistance with the manuscript. The Microarray Shared Resource and the Genotyping Shared Resource of the Mayo Clinic Advanced Genomic Technology Center, respectively, did all the genome-wide association and gene-expression analyses described in this study. This study was supported by US National Institutes of Health research grants R01-CA80127 (to PY), R01-CA84354 (to PY), CA111646 (to XW), CA127615 (to XW), CA055769 (to MRS), CA092824 (to DCC), CA074386 (to DCC), CA090578 (to DCC), P50 CA90833 (to ZFZ), T32 CA09142 (to ZFZ). and Mayo Foundation funds (to PY and JJ). NR 47 TC 114 Z9 120 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2010 VL 11 IS 4 BP 321 EP 330 DI 10.1016/S1470-2045(10)70042-5 PG 10 WC Oncology SC Oncology GA 584PQ UT WOS:000276765100018 PM 20304703 ER PT J AU Bose, D Meric-Bernstam, F Hofstetter, W Reardon, DA Flaherty, KT Ellis, LM AF Bose, Debashish Meric-Bernstam, Funda Hofstetter, Wayne Reardon, David A. Flaherty, Keith T. Ellis, Lee M. TI Vascular endothelial growth factor targeted therapy in the perioperative setting: implications for patient care SO LANCET ONCOLOGY LA English DT Review ID METASTATIC COLORECTAL-CANCER; RENAL-CELL CARCINOMA; BEVACIZUMAB PLUS IRINOTECAN; OXALIPLATIN-BASED CHEMOTHERAPY; TYROSINE KINASE INHIBITOR; REFRACTORY SOLID TUMORS; RANDOMIZED PHASE-III; LIVER METASTASES; MALIGNANT GLIOMAS; BREAST-CANCER AB Vascular endothelial growth factor (VEGF) targeted therapy, either alone or in combination with chemotherapy, has become the standard of care in several solid tumours, including colorectal cancer, renal-cell carcinoma, breast cancer, non-small-cell lung cancer, and glioblastoma. VEGF is crucial in the process of angiogenesis and wound healing and, thus, its inhibition has the potential to affect wound healing in patients undergoing surgery. In this review, we summarise the data available on the use of VEGF-targeted therapies, and their effect on perioperative wound complications. Surgery in patients receiving VEGF-targeted therapies seems to be safe when an appropriate interval of time is allowed between surgical procedures and treatment. Recommendations regarding this interval are provided in a disease and agent site-specific manner. We also discuss complications arising from the use of VEGF-directed therapies that might require surgical intervention and the considerations important in their management. At this juncture, safety data on the use of VEGF-targeted therapies in the perioperative period are sparse, and investigators are urged to continue to study this issue prospectively in current and future clinical trials to establish firm guidelines. C1 [Bose, Debashish; Meric-Bernstam, Funda; Ellis, Lee M.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77230 USA. [Hofstetter, Wayne] Univ Texas MD Anderson Canc Ctr, Dept Thorac Surg, Houston, TX 77230 USA. [Bose, Debashish; Ellis, Lee M.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77230 USA. [Reardon, David A.] Duke Univ, Sch Med, Dept Pediat, Durham, NC USA. [Reardon, David A.] Duke Univ, Sch Med, Dept Surg, Durham, NC USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. RP Ellis, LM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, POB 301402, Houston, TX 77230 USA. EM lellis@mdanderson.org FU NCI NIH HHS [P30 CA016672] NR 95 TC 63 Z9 68 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2010 VL 11 IS 4 BP 373 EP 382 DI 10.1016/S1470-2045(09)70341-9 PG 10 WC Oncology SC Oncology GA 584PQ UT WOS:000276765100024 PM 20171141 ER PT J AU Honings, J Stephen, AE Marres, HA Gaissert, HA AF Honings, Jimmie Stephen, Antonia E. Marres, Henri A. Gaissert, Henning A. TI The Management of Thyroid Carcinoma Invading the Larynx or Trachea SO LARYNGOSCOPE LA English DT Review DE Thyroid carcinoma; laryngotracheal invasion; surgical management; segmental airway resection; long-term outcome ID LARYNGOTRACHEAL INVASION; SURGICAL-MANAGEMENT; PAPILLARY CARCINOMA; AIRWAY INVASION; INITIAL MANIFESTATIONS; RESECTIONAL MANAGEMENT; EXTERNAL RADIOTHERAPY; PATHOLOGICAL FINDINGS; AERODIGESTIVE TRACT; CANCER AB Objectives/Hypothesis: To describe the controversies in the management of thyroid carcinoma; invading the airway. Study Design: Contemporary review of literature, level of evidence: 5. Results: Invasion of the larynx or trachea by thyroid carcinoma is uncommon and often identified at the time of operation, when the surgeon must decide the extent of resection. Invasion of the airway is associated with loss of tumor differentiation and a reduction in long-term survival compared to tumors limited to the thyroid gland. Whether or not the invaded airway should be resected remains controversial. Tangential shave excision of tumor is commonly performed, despite a marked risk of local recurrence. Circumferential sleeve resection of the larynx and trachea is safe and lowers the risk of local recurrence. In recurrent disease, laryngotracheal resection provides effective palliation of airway obstruction and hemoptysis. Conclusions: Long-term (>10-20 years) prospective studies are required to compare the outcome after; shave excision with segmental airway resection for thyroid carcinoma Based on the current literature and on our experience, we advocate circumferential tracheal resection in the setting of airway involvement. C1 [Honings, Jimmie; Gaissert, Henning A.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Stephen, Antonia E.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Honings, Jimmie; Marres, Henri A.] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, NL-6525 ED Nijmegen, Netherlands. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,32 Fruit St, Boston, MA 02114 USA. RI Marres, H.A.M./H-8071-2014; Honings, Jimmie/B-3639-2016 OI Honings, Jimmie/0000-0001-5077-3472 NR 61 TC 25 Z9 28 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2010 VL 120 IS 4 BP 682 EP 689 DI 10.1002/lary.20800 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 578ZG UT WOS:000276335100007 PM 20213659 ER PT J AU Lin, HW Bhattacharyya, N AF Lin, Harrison W. Bhattacharyya, Neil TI Clinical Behavior of Follicular Variant of Papillary Thyroid Carcinoma: Presentation and Survival SO LARYNGOSCOPE LA English DT Article DE Thyroid carcinoma; staging; survival; prognosis ID PROGNOSTIC-FACTORS; FEATURES; CANCER AB Objectives/Hypothesis: To determine the prevalence and extent of disease characteristics of the follicular variant of papillary thyroid carcinoma (FV-PTC) and the survival impact of this histopathological diagnosis compared to classical papillary thyroid carcinoma (C-PTC) Study Design: Cross-sectional population analysis of a national cancer database. Methods: Cases of C-PTC and FV-PTC were extracted from the Surveillance, Epidemiology and End Results database for 1988 to 2006 and staged. Surgical extent and radioactive iodine (RAT) use were determined Demographic and staging parameters were statistically compared according to tumor histology. Survival differences according to histology were determined with a Cox proportional hazards model, adjusting for age, sex, T stage, N stage, surgical therapy, and RAT. Results: A total of 46,699 patients were identified (68.4% C-PTC and 31.6% FV-PTC). Age at presentation and sex distribution were similar between FV-PTC (47.9 years; 79.3% female) and C-PTC patients (46.2 years; 77.3% female). Although nodal disease prevalence was significantly lower in FV-PTC compared to C-PTC (14.8%. vs 27.8%, respectively; P < 001), T stage was not significantly different (P = .450). Mean overall survivals for patients with FV-PTC (204 5 months) and C-PTC (205 3 months) were not significantly different (P = .373). Cox regression analysis revealed that advanced age (P < .001), male sex (P < .001), advanced T stage (P < .001), and positive nodal disease (P < 001) were associated with reduced overall survival, whereas histopathological subtype was not (P = 360). Conclusions: Disease presentation (with exception of nodal metastasis) and survival in patients with FV-PTC are statistically similar to that of C-PTC, and accordingly these patients carry very similar prognoses C1 [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Lin, Harrison W.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, 45 Francis St, Boston, MA 02115 USA. NR 21 TC 25 Z9 25 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2010 VL 120 IS 4 BP 712 EP 716 DI 10.1002/lary.20828 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 578ZG UT WOS:000276335100012 PM 20205241 ER PT J AU Akahane, K Inukai, T Inaba, T Kurosawa, H Look, AT Kiyokawa, N Fujimoto, J Goto, H Endo, M Zhang, X Hirose, K Kuroda, I Honna, H Kagami, K Goi, K Nakazawa, S Sugita, K AF Akahane, K. Inukai, T. Inaba, T. Kurosawa, H. Look, A. T. Kiyokawa, N. Fujimoto, J. Goto, H. Endo, M. Zhang, X. Hirose, K. Kuroda, I. Honna, H. Kagami, K. Goi, K. Nakazawa, S. Sugita, K. TI Specific induction of CD33 expression by E2A-HLF: the first evidence for aberrant myeloid antigen expression in ALL by a fusion transcription factor SO LEUKEMIA LA English DT Letter ID ACUTE-LYMPHOBLASTIC-LEUKEMIA; CHILDHOOD C1 [Akahane, K.; Inukai, T.; Zhang, X.; Hirose, K.; Kuroda, I.; Honna, H.; Kagami, K.; Goi, K.; Nakazawa, S.; Sugita, K.] Univ Yamanashi, Dept Pediat, Sch Med, Yamanashi, Japan. [Inaba, T.] Hiroshima Univ, Dept Mol Oncol, Res Inst Radiat Biol & Med, Hiroshima, Japan. [Kurosawa, H.] Dokkyo Med Univ, Sch Med, Dept Pediat, Mibu, Tochigi, Japan. [Look, A. T.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kiyokawa, N.; Fujimoto, J.] Natl Res Inst Child Hlth & Dev, Dept Dev Biol, Tokyo, Japan. [Goto, H.] Yokohama City Univ, Sch Med, Dept Pediat, Yokohama, Kanagawa 232, Japan. [Endo, M.] Iwate Med Univ, Sch Med, Dept Pediat, Morioka, Iwate 020, Japan. RP Akahane, K (reprint author), Univ Yamanashi, Dept Pediat, Sch Med, Yamanashi, Japan. EM tinukai@yamanashi.ac.jp NR 8 TC 3 Z9 3 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2010 VL 24 IS 4 BP 865 EP 869 DI 10.1038/leu.2010.8 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 583IB UT WOS:000276666200028 PM 20147975 ER PT J AU Sifri, CD Sun, HY Cacciarelli, TV Wispelwey, B Pruett, TL Singh, N AF Sifri, Costi D. Sun, Hsin-Yun Cacciarelli, Thomas V. Wispelwey, Brian Pruett, Timothy L. Singh, Nina TI Pretransplant Cryptococcosis and Outcome After Liver Transplantation SO LIVER TRANSPLANTATION LA English DT Article ID CALCINEURIN-INHIBITOR AGENTS; NEOFORMANS INFECTION; ACTIVATED MACROPHAGES; DRUG-INTERACTIONS; RENAL-ALLOGRAFT; IFN-GAMMA; RECIPIENTS; PULMONARY; MICE; INTERLEUKIN-4 AB The posttransplant outcomes and optimal management of patients with end-stage liver disease who develop cryptococcosis prior to transplantation have not been defined. We discuss these issues in the context of successful liver transplantation and pretransplant cryptococcal disease. Our report suggests that liver transplantation may be cautiously considered under the umbrella of fluconazole therapy in patients with end-stage liver disease and pretransplant cryptococcosis, provided that disease control is achieved with adequate treatment before transplantation. Liver Transpl 16:499-502, 2010. (C) 2010 AASLD. C1 [Sifri, Costi D.; Wispelwey, Brian; Pruett, Timothy L.] Univ Virginia, Charlottesville, VA USA. [Sun, Hsin-Yun; Cacciarelli, Thomas V.; Singh, Nina] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Dept Internal Med, Natl Taiwan Univ Hosp, Taipei, Taiwan. [Cacciarelli, Thomas V.; Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA. RP Singh, N (reprint author), Vet Adm Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu OI SUN, HSIN-YUN/0000-0003-0074-7721 NR 31 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD APR PY 2010 VL 16 IS 4 BP 499 EP 502 DI 10.1002/lt.22024 PG 4 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 582BN UT WOS:000276570300015 PM 20373460 ER PT J AU Jordan, KW Adkins, CB Su, L Halpern, EF Mark, EJ Christiani, DC Cheng, LL AF Jordan, K. W. Adkins, C. B. Su, L. Halpern, E. F. Mark, E. J. Christiani, D. C. Cheng, L. L. TI Comparison of squamous cell carcinoma and adenocarcinoma of the lung by metabolomic analysis of tissue-serum pairs SO LUNG CANCER LA English DT Article DE Lung squamous cell carcinoma; Lung adenocarcinoma; Diagnosis; Magnetic resonance spectroscopy; Magic angle spinning; Metabolomics; Blood serum ID MAGNETIC-RESONANCE-SPECTROSCOPY; FDG PET; CANCER AB The prospect of establishing serum metabolomic profiles offers great clinical significance for its potential to detect human lung cancers at clinically asymptomatic stages. Patients with suspicious serum metabolomic profiles may undergo advanced radiological tests that are too expensive to be employed as screening tools for the mass population. As the first step to establishing such profiles, this study investigates correlations between tissue and serum metabolomic profiles for squamous cell carcinoma (SCC) and adenocarcinoma (AC) in the lungs of humans. Tissue and serum paired samples from 14 patients (five SCCs and nine ACs), and seven serum samples from healthy controls were analyzed with high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS (1)HMRS). Tissue samples were subjected to quantitative histological pathology analyses after MRS. Based on pathology results, tissue metabolomic profiles for the evaluated cancer types were established using principal component and canonical analyses on measurable metabolites. The parameters used to construct tissue cancer profiles were then tested with serum spectroscopic results for their ability to differentiate between cancer types and identify cancer from controls. In addition, serum spectroscopic results were also analyzed independent of tissue data. Our results strongly indicate the potential of serum MR spectroscopy to achieve the task of differentiating between the tested human lung cancer types and from controls. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Jordan, K. W.; Adkins, C. B.; Mark, E. J.; Cheng, L. L.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Halpern, E. F.; Cheng, L. L.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Christiani, D. C.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Su, L.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Cheng, LL (reprint author), CNY 7,149 13th St, Charlestown, MA 02129 USA. EM cheng@nmr.mgh.harvard.edu OI Jordan, Kate/0000-0002-3089-2543 FU NIH [CA115746, CA095624, CA092824, CA074386, CA090578]; MGH A.A. Martinos Center for Biomedical Imaging FX Authors acknowledge partial support by NIH grants CA115746 (LLC), CA095624 (LLC), CA092824 (DCC), CA074386 (DCC), CA090578 (DCC), and MGH A.A. Martinos Center for Biomedical Imaging. NR 10 TC 29 Z9 31 U1 1 U2 20 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD APR PY 2010 VL 68 IS 1 BP 44 EP 50 DI 10.1016/j.lungcan.2009.05.012 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 579NN UT WOS:000276378400007 PM 19559498 ER PT J AU Liu, ST Fleysher, R Fleysher, L Joo, CG Ratai, EM Gonzalez, RG Gonen, O AF Liu, Songtao Fleysher, Roman Fleysher, Lazar Joo, Chan-Gyu Ratai, Eva-Maria Gonzalez, R. Gilberto Gonen, Oded TI Brain Metabolites B-1-Corrected Proton T-1 Mapping in the Rhesus Macaque at 3 T SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE brain MR spectroscopy; brain metabolites; B-1 mapping; longitudinal relaxation time; rhesus macaque; T-1 ID RELAXATION-TIMES; IN-VIVO; MR SPECTROSCOPY; ADIABATIC PULSES; MAGNETIC-FIELDS; QUANTIFICATION; ACQUISITION; SUPPRESSION; RESOLUTION; REDUCTION AB The accuracy of metabolic quantification in MR spectroscopy is limited by the unknown radiofrequency field and T-1. To address both issues in proton (H-1) MR spectroscopy, we obtained radiofrequency field-corrected T-1 maps of N-acetylaspartate, choline, and creatine in five healthy rhesus macaques at 3 T. For efficient use of the 4 hour experiment, we used a new three-point protocol that optimizes the precision of T-1 in three-dimensional H-1-MR spectroscopy localization for extensive, similar to 30%, brain coverage at 0.6 x 0.6 x 0.5 cm(3) = 180-mu L spatial resolution. The resulting mean T(1)s in 700 voxels were N-acetylaspartate = 1232 +/- 44, creatine = 1238 +/- 23 and choline = 1107 +/- 56 ms (mean standard error of the mean). Their histograms from all 140 voxels in each animal were similar in position and shape, characterized by standard errors of the mean of the full width at half maximum divided by their means of better than 8%. Regional gray matter N-acetylaspartate, choline, and creatine T(1)s (1333 +/- 43, 1265 +/- 52, and 1131 +/- 28 ms) were 5-10% longer than white matter: 1188 +/- 34, 1201 +/- 24, and 1082 +/- 50 ms (statistically significant for the N-acetylaspartate only), all within 10% of the corresponding published values in the human brain. Magn Reson Med 63:865-871, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Liu, Songtao; Fleysher, Roman; Fleysher, Lazar; Gonen, Oded] NYU, Sch Med, Dept Radiol, New York, NY 10016 USA. [Joo, Chan-Gyu; Ratai, Eva-Maria; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Joo, Chan-Gyu; Ratai, Eva-Maria; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Neuroradiol Div, Charlestown, MA USA. RP Gonen, O (reprint author), NYU, Sch Med, Dept Radiol, 660 1st Ave,4th Floor, New York, NY 10016 USA. EM oded.gonen@med.nyu.edu OI Gonen, Oded/0000-0002-3148-2028 FU National Institutes of Health [EB01015, NS050520, NS050041, NS051129, NS059331, AI028691, NS040237]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery (MIND) Institute FX Grant sponsor: National Institutes of Health; Grant numbers: EB01015, NS050520, NS050041, NS051129, NS059331, AI028691, NS040237.; We thank Drs. Andrew A. Maudsley of the University of Miami and Brian J. Soher of Duke University for their SITools-FITT software and Dr. Joanne Morris and Ms. Shannon Luboyeski for animal veterinary care. The MGH A.A. Martinos Center for Biomedical Imaging is also supported by National Center for Research Resources grant number P41RR14075 and the Mental Illness and Neuroscience Discovery (MIND) Institute. NR 35 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 2010 VL 63 IS 4 BP 865 EP 871 DI 10.1002/mrm.22270 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 575JW UT WOS:000276064300003 PM 20373387 ER PT J AU Barth, M Meyer, H Kannengiesser, SAR Polimeni, JR Wald, LL Norris, DG AF Barth, Markus Meyer, Heiko Kannengiesser, Stephan A. R. Polimeni, Jonathan R. Wald, Lawrence L. Norris, David G. TI T-2-Weighted 3D fMRI Using S-2-SSFP at 7 Tesla SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE BOLD; 7 tesla; brain; neuroimaging; steady-state free procession ID STATE FREE PRECESSION; HUMAN VISUAL-CORTEX; SPIN-ECHO FMRI; HUMAN BRAIN; FUNCTIONAL MRI; STEADY-STATE; NOISE CHARACTERISTICS; PARALLEL MRI; HIGH-FIELD; BOLD FMRI AB In this study, the sensitivity of the S-2-steady-state free precession (SSFP) signal for functional MRI at 7 T was investigated. In order to achieve the necessary temporal resolution, a three-dimensional acquisition scheme with acceleration along two spatial axes was employed. Activation maps based on S-2-steady-state free precession data showed similar spatial localization of activation and sensitivity as spin-echo echo-planar imaging (SE-EPI), but data can be acquired with substantially lower power deposition. The functional sensitivity estimated by the average z-values was not significantly different for SE-EPI compared to the S-2-signal but was slightly lower for the S-2-signal (6.74 +/- 0.32 for the TR = 15 ms protocol and 7.51 +/- 0.78 for the TR = 27 ms protocol) compared to SE-EPI (7.49 +/- 1.44 and 8.05 +/- 1.67) using the same activated voxels, respectively. The relative signal changes in these voxels upon activation were slightly lower for SE-EPI (2.37% +/- 0.18%) compared to the TR = 15 ms S-2-SSFP protocol (2.75% +/- 0.53%) and significantly lower than the TR = 27 ms protocol (5.38% +/- 1.28%), in line with simulations results. The large relative signal change for the long TR SSFP protocol can be explained by contributions from multiple coherence pathways and the low intrinsic intensity of the S-2 signal. In conclusion, whole-brain T-2-weighted functional MRI with negligible image distortion at 7 T is feasible using the S-2-SSFP sequence and partially parallel imaging. Magn Reson Med 63:1015-1020, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Barth, Markus; Norris, David G.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, NL-6500 HB Nijmegen, Netherlands. [Barth, Markus; Norris, David G.] Univ Duisburg Essen, EL Hahn Inst Magnet Resonance Imaging, Essen, Germany. [Meyer, Heiko; Kannengiesser, Stephan A. R.] Siemens Healthcare, MR Applicat Dev, Erlangen, Germany. [Polimeni, Jonathan R.; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr, Charlestown, MA USA. [Polimeni, Jonathan R.; Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Barth, M (reprint author), Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM markus.barth@donders.ru.nl RI Norris, David/A-1937-2010; Barth, Markus/B-8446-2008; Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Norris, David/0000-0002-3699-6917; Barth, Markus/0000-0002-0520-1843; Polimeni, Jonathan/0000-0002-1348-1179; FU National Institutes of Health [NCRR P41RR14075, NIBIB R01E8006847]; Siemens Medical Solutions FX Grant sponsor: National Institutes of Health; Grant number: NCRR P41RR14075 and NIBIB R01E8006847.; Two authors (J.R.P. and L.L.W.) acknowledge support from National Institutes of Health grants: NCRR P41RR14075, NIBIB R01EB006847 and research support from Siemens Medical Solutions. One of the authors (LLW) has obtained consulting income from Siemens Healthcare. We are also grateful for Kyoko Fujimoto's organizational as well as Benedikt Poser's and Thomas Witzers measurement support. NR 28 TC 18 Z9 18 U1 0 U2 4 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 APR PY 2010 VL 63 IS 4 BP 1015 EP 1020 DI 10.1002/mrm.22283 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 575JW UT WOS:000276064300019 PM 20373402 ER PT J AU Otsuka, S Namiki, Y Ichii, O Hashimoto, Y Sasaki, N Endoh, D Kon, Y AF Otsuka, Saori Namiki, Yuka Ichii, Osamu Hashimoto, Yoshiharu Sasaki, Nobuya Endoh, Daiji Kon, Yasuhiro TI Analysis of factors decreasing testis weight in MRL mice SO MAMMALIAN GENOME LA English DT Article ID METAPHASE-SPECIFIC APOPTOSIS; MISMATCH REPAIR PROTEINS; HUMAN EXONUCLEASE-I; CHROMOSOME SYNAPSIS; SPINDLE CHECKPOINT; MEIOTIC PROPHASE; MRL/MPJ MICE; CELL-DEATH; MOUSE; SPERMATOCYTES AB MRL/MpJ (MRL) mouse testes have several unique characteristics, including the appearance of oocytes, the occurrence of metaphase-specific apoptosis of meiotic spermatocytes, and the presence of heat-shock-resistant spermatocytes. In the present study we used chromosomal mapping to determine the genomic background associated with small testis size in MRL mice. We prepared and analyzed C57BL/6-based congenic mice carrying MRL mouse loci. Quantitative trait loci (QTL) analysis revealed susceptibility loci for small testis size at 100 cM on chromosome (Chr) 1 and at around 80 cM on Chr 2. Analysis with B6.MRLc1 and B6.MRLc2 congenic mice and double-congenic mice confirmed the QTL data and showed that low testis weight in MRL mice was caused by germ cell apoptosis. Through histological examinations we found that B6.MRLc1 and B6.MRLc2 mice showed stage-specific apoptosis in their testes, the former at metaphase stage XII and the later at pachytene stage IV. Metaphase-specific apoptosis of spermatocytes occurs due to mutation of the exonuclease 1 (Exo1) gene located at 100 cM on Chr 1. Thus, the mutation of the Exo1 gene is also responsible for low testis weight caused by metaphase-specific apoptosis. In conclusion, testis weight is reduced in MRL mice due to apoptosis of germ cells caused by mutations in loci on Chrs 1 and 2. C1 [Otsuka, Saori; Ichii, Osamu; Hashimoto, Yoshiharu; Kon, Yasuhiro] Hokkaido Univ, Anat Lab, Grad Sch Vet Med, Kita Ku, Sapporo, Hokkaido 0600818, Japan. [Otsuka, Saori; Hashimoto, Yoshiharu] Hokkaido Univ, Off Fac Dev & Teaching Enriched Vet Med, Grad Sch Vet Med, Sapporo, Hokkaido 0600818, Japan. [Namiki, Yuka] Harvard Univ, Dept Mol Biol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Sasaki, Nobuya] Hokkaido Univ, Lab Expt Anim Sci, Grad Sch Vet Med, Sapporo, Hokkaido 0600818, Japan. [Endoh, Daiji] Rakuno Gakuen Univ, Dept Vet Radiol, Sch Vet Med, Ebetsu, Hokkaido 0698501, Japan. RP Kon, Y (reprint author), Hokkaido Univ, Anat Lab, Grad Sch Vet Med, Kita Ku, Kita 18,Nishi 9, Sapporo, Hokkaido 0600818, Japan. EM y-kon@vetmed.hokudai.ac.jp RI Sasaki, Nobuya/F-6579-2012; Otsuka, Saori/F-8531-2012; Kon, Yasuhiro/F-8525-2012 FU Ministry of Education, Culture, Sports, Science, and Technology of Japan [16380194, 19380162, 19658106] FX This study was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (16380194, 19380162, and 19658106). NR 43 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 2010 VL 21 IS 3-4 BP 153 EP 161 DI 10.1007/s00335-010-9251-0 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 574LN UT WOS:000275990800004 PM 20157820 ER PT J AU Caplan, L Pittman, CB Zeringue, AL Scherrer, JF Wehmeier, KR Cunningham, FE Eisen, SA McDonald, JR AF Caplan, Liron Pittman, Cory B. Zeringue, Angelique L. Scherrer, Jeffrey F. Wehmeier, Kent R. Cunningham, Francesca E. Eisen, Seth A. McDonald, Jay R. TI An Observational Study of Musculoskeletal Pain Among Patients Receiving Bisphosphonate Therapy SO MAYO CLINIC PROCEEDINGS LA English DT Article ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; POSTMENOPAUSAL OSTEOPOROSIS; ZOLEDRONIC ACID; PRACTICE PATTERNS; PAGETS-DISEASE; RISEDRONATE; PREVENTION; BONE; PERSISTENCE; ALENDRONATE AB OBJECTIVE. To seek evidence for the association of bisphosphonate use with diffuse musculoskeletal pain (MSKP) in a large national cohort, controlling for conditions associated with MSKP. PATIENTS AND METHODS This retrospective cohort study enrolled all US veterans aged 65 years or older with a vertebral or hip fracture who were treated for at least 1 year between October 1, 1998, and September 30, 2006 (N=26,545). All International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes, demographics, and pharmaceutical data were obtained from national databases. A composite end point, based on ICD-9-CM codes compatible with diffuse MSKP, was constructed. The primary outcome was time until MSKP. We performed regression analysis using the Cox proportional hazards model, controlling for age, sex, race, alcoholism, depression, anxiety, smoking, recent 3-hydroxy-3-methylglutaryi coenzyme A reductase inhibitor (statin) use, rheumatic disease, and comorbidity score. RESULTS The univariate regression identified an association of bisphosphonate exposure and MSKP (hazard ratio, 1.22; 95% confidence interval, 1.04-1.44). In the multivariate regression, however, patients prescribed a bisphosphonate were not more likely to be assigned an ICD-9-CM code compatible with diffuse MSKP (hazard ratio. 1.10; 95% confidence interval, 0.93-1.30). Consistent with prior studies, we found that female sex, depression, anxiety, comorbidity score, and the presence of a rheumatic disease were all associated with a greater risk of a diagnosis of diffuse MSKP. There was no demonstrable association with statin exposure. CONCLUSION Bisphosphonate use was not associated with a statistically higher rate of MSKP in this cohort. Individual patients may rarely report MSKP while taking bisphosphonates; however, for our studied cohort. incident MSKP does not appear to explain bisphosphonate discontinuation rates C1 [Caplan, Liron] Univ Colorado, Dept Med, Denver Vet Affairs Med Ctr, Denver, CO 80045 USA. [Pittman, Cory B.] Mercy Arthrit & Osteoporosis Ctr, Urbandale, IA USA. [Zeringue, Angelique L.; McDonald, Jay R.] Washington Univ, Sch Med, Dept Med, St Louis Vet Affairs Med Ctr, St Louis, MO 63110 USA. [Scherrer, Jeffrey F.] Washington Univ, Sch Med, Dept Psychiat, St Louis Vet Affairs Med Ctr, St Louis, MO 63110 USA. [Wehmeier, Kent R.] Univ Florida, Dept Med, Coll Med Jacksonville, Jacksonville, FL USA. [Cunningham, Francesca E.] Vet Affairs Pharm Benefits Management, Hines, IL USA. [Eisen, Seth A.] Vet Affairs Hlth Serv Res & Dev, Washington, DC USA. RP Caplan, L (reprint author), Univ Colorado, Dept Med, Denver Vet Affairs Med Ctr, POB 6511,B115, Denver, CO 80045 USA. RI Zeringue, Angelique/I-1755-2012 FU US Department of Veterans Affairs [IAF 06-026-2]; National Institutes of Health [KL2RR024994]; VA Health Services Research & Development (HSRD) FX Funding support for this research was provided by the US Department of Veterans Affairs (VA) Merit Review Grant IAF 06-026-2 Dr McDonald is supported in part by National Institutes of Health grant KL2RR024994 Dr Caplan is supported by a VA Health Services Research & Development (HSR&D) grant, however, the funding sources had no role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the manuscript for publication NR 27 TC 10 Z9 10 U1 1 U2 4 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD APR PY 2010 VL 85 IS 4 BP 341 EP 348 DI 10.4065/mcp.2009.0492 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 578ZZ UT WOS:000276337100005 PM 20231335 ER PT J AU Dunlap, LJ Zarkin, GA Bray, JW Mills, M Kivlahan, DR McKay, JR Latham, P Tonigan, JS AF Dunlap, Laura J. Zarkin, Gary A. Bray, Jeremy W. Mills, Michael Kivlahan, Daniel R. McKay, James R. Latham, Patricia Tonigan, J. Scott TI Revisiting the Cost-Effectiveness of the COMBINE Study for Alcohol Dependent Patients The Patient Perspective SO MEDICAL CARE LA English DT Article DE alcohol treatment; cost-effectiveness; patient costs ID EFFECTIVENESS ACCEPTABILITY CURVES; COMBINED PHARMACOTHERAPIES; BEHAVIORAL INTERVENTIONS; DRUG-TREATMENT; FORM 90; TIME; RELIABILITY; SEEKING; CANCER; TRIAL AB Objective: Most cost and cost-effectiveness studies of substance abuse treatments focus on the costs to the provider/payer. Although this perspective is important, the costs incurred by patients should also be considered when evaluating treatment. This article presents estimates of patients' costs associated with the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) alcohol treatments and evaluates the treatments' cost-effectiveness from the patient perspective. Study Design: A prospective cost-effectiveness study of patients in COMBINE, a randomized controlled clinical trial of 9 alternative alcohol treatment regimens involving 1383 patients with diagnoses of primary alcohol dependence across 11 US clinic sites. We followed a microcosting approach that allowed estimation of patients' costs for specific COMBINE treatment activities. The primary clinical outcomes from COMBINE are used as indicators of treatment effectiveness. Results: The average total patient time devoted to treatment ranged from about 30 hours to 46 hours. Time spent traveling to and from treatment sessions and participation in self-help meetings accounted for the largest portion of patient time costs. The cost-effectiveness results indicate that 6 of the 9 treatments were economically dominated and only 3 treatments are potentially cost-effective depending on patient's willingness to pay for the considered outcomes: medical management (MM) + placebo, MM + naltrexone, and MM + naltrexone + acamprosate. Conclusions: Few studies consider the patient's perspective in estimating costs and cost-effectiveness even though these costs may have a substantial impact on a patient's treatment choice, ability to access treatment, or treatment adherence. For this study, the choice of the most cost-effective treatment depends on the value placed on the outcomes by the patient, and the conclusions drawn by the patient may differ from that of the provider/payer. C1 [Dunlap, Laura J.; Zarkin, Gary A.; Bray, Jeremy W.; Mills, Michael] RTI Int, Res Triangle Pk, NC USA. [Kivlahan, Daniel R.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [McKay, James R.] Univ Penn, Dept Psychiat, Ctr Continuum Care, Philadelphia, PA 19104 USA. [McKay, James R.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Latham, Patricia] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Tonigan, J. Scott] Univ New Mexico, Ctr Alchoholism Subst Abuse & Addict, Albuquerque, NM 87131 USA. RP Dunlap, LJ (reprint author), RTI Int, 6110 Execut Blvd,Suite 902, Rockville, MD 20852 USA. EM ljd@rti.org FU National Institute on Alcohol Abuse and Alcoholism [1-R01-AA12788] FX This study was supported by grant 1-R01-AA12788 from the National Institute on Alcohol Abuse and Alcoholism. NR 29 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 2010 VL 48 IS 4 BP 306 EP 313 DI 10.1097/MLR.0b013e3181ca3d40 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 582ZE UT WOS:000276639300004 PM 20355261 ER PT J AU Elkin, EB Ishill, NM Snow, JG Panageas, KS Bach, PB Liberman, L Wang, FH Schrag, D AF Elkin, Elena B. Ishill, Nicole M. Snow, Jacqueline G. Panageas, Katherine S. Bach, Peter B. Liberman, Laura Wang, Fahui Schrag, Deborah TI Geographic Access and the Use of Screening Mammography SO MEDICAL CARE LA English DT Article DE breast cancer; screening; mammography; access; geographic information systems (GIS) ID BREAST-CANCER SURVIVORS; QUALITY STANDARDS ACT; ELDERLY-WOMEN; INTERVENTIONS; GUIDELINES; AMERICAN; IMPACT; OLDER; RECOMMENDATION; METAANALYSIS AB Background: Screening mammography rates vary geographically and have recently declined. Inadequate mammography resources in some areas may impair access to this technology. We assessed the relationship between availability of mammography machines and the use of screening. Methods: The location and number of all mammography machines in the United States were identified from US Food and Drug Administration records of certified facilities. Inadequate capacity was defined as <1.2 mammography machines per 10,000 women age 40 or older, the threshold required to meet the Healthy People 2010 target screening rate. The impact of capacity on utilization was evaluated in 2 cohorts: female respondents age 40 or older to the 2006 Behavioral Risk Factor Surveillance System survey (BRFSS) and a 5% nationwide sample of female Medicare beneficiaries age 65 or older in 2004-2005. Results: About 9% of women in the BRFSS cohort and 13% of women in the Medicare cohort lived in counties with <1.2 mammography machines per 10,000 women age 40 or older. In both cohorts, residence in a county with inadequate mammography capacity was associated with lower odds of a recent mammogram ( adjusted odds ratio in BRFSS: 0.89, 95% CI: 0.80-0.98, P < 0.05; adjusted odds ratio in Medicare: 0.86, 95% CI: 0.85-0.87, P < 0.05), controlling for demographic and health care characteristics. Conclusion: In counties with few or no mammography machines, limited availability of imaging resources may be a barrier to screening. Efforts to increase the number of machines in low-capacity areas may improve mammography rates and reduce geographic disparities in breast cancer screening. C1 [Elkin, Elena B.] Mem Sloan Kettering Canc Ctr, Hlth Outcomes Res Grp, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Liberman, Laura] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Wang, Fahui] Louisiana State Univ, Dept Geog & Anthropol, Baton Rouge, LA 70803 USA. [Schrag, Deborah] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA. RP Elkin, EB (reprint author), Mem Sloan Kettering Canc Ctr, Hlth Outcomes Res Grp, Dept Epidemiol & Biostat, 1275 York Ave,Box 44, New York, NY 10021 USA. EM elkine@mskcc.org RI Wang, Fahui/H-4302-2013 FU Susan G. Komen for the Cure [POP107806, PI: Elkin]; American Cancer Society [MRSG-06-127-01-CPHPS, PI: Elkin]; National Cancer Institute [K07-CA118189, PI: Elkin] FX Supported by grants from Susan G. Komen for the Cure (POP107806, PI: Elkin), the American Cancer Society (MRSG-06-127-01-CPHPS, PI: Elkin), and the National Cancer Institute (K07-CA118189, PI: Elkin). NR 50 TC 47 Z9 49 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 2010 VL 48 IS 4 BP 349 EP 356 DI 10.1097/MLR.0b013e3181ca3ecb PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 582ZE UT WOS:000276639300010 PM 20195174 ER PT J AU Hivert, MF Sullivan, LM Shrader, P Fox, CS Nathan, DM D'Agostino, RB Wilson, PWF Benjamin, EJ Meigs, JB AF Hivert, Marie-France Sullivan, Lisa M. Shrader, Peter Fox, Caroline S. Nathan, David M. D'Agostino, Ralph B., Sr. Wilson, Peter W. F. Benjamin, Emelia J. Meigs, James B. TI The association of tumor necrosis factor alpha receptor 2 and tumor necrosis factor alpha with insulin resistance and the influence of adipose tissue biomarkers in humans SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID C-REACTIVE PROTEIN; TNF-ALPHA; METABOLIC SYNDROME; IN-VITRO; 3T3-L1 ADIPOCYTES; HEART-DISEASE; ADIPONECTIN; PLASMA; EXPRESSION; CYTOKINES AB Tumor necrosis factor alpha (TNF alpha) is a proinflammatory adipokine hypothesized to link obesity with insulin resistance. Functional studies suggest that TNF alpha acts through pathways involving adipokines and fatty acids to induce insulin resistance. We tested the hypothesis that the association of measures of TNF alpha activity with insulin resistance is independent of obesity and adipose tissue biomarkers. We analyzed data from 2131 participants (without diabetes) of the Framingham Offspring Study examination 7. The outcome of interest was insulin resistance, measured using the homeostasis model assessment (HOMA-IR). Tumor necrosis factor alpha activity was measured by plasma tumor necrosis factor alpha receptor 2 (TNFr2) or TNF alpha; possible confounders included adipose tissue biomarkers (plasma adiponectin, resistin, and triglycerides). We used multivariable age- and sex-adjusted linear regression analyses to adjust for waist circumference and for biomarkers individually and simultaneously, and in biomarker-stratified (above and below median) models. We found that TNFr2 was positively associated with HOMA-IR (r = 0.21, P < .0001). In age- and sex-adjusted model, for each increase of 1 standard deviation of TNFr2 (SD = 746 pg/mL), the log (HOMA-IR) value was increased by 0.11 units (P < .0001). Adjustment for waist circumference reduced the TNFr2 beta-coefficient (by about 45%), but the association between TNFr2 and HOMA-IR remained significant (P < .0001). Tumor necrosis factor a receptor 2 was still associated to HOMA-IR after adding adiponectin, resistin, and triglycerides (individually and simultaneously). We found similar associations with plasma levels of TNF alpha. We conclude that, in a representative community sample, measures of TNF alpha activity are associated with insulin resistance, even after accounting for central adiposity and other adipose tissue biomarkers. (C) 2010 Elsevier Inc. All rights reserved. C1 [Hivert, Marie-France; Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Hivert, Marie-France; Nathan, David M.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol & Metab, Boston, MA 02115 USA. [Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Dept Med, Boston, MA 02114 USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Consulting Unit, Boston, MA 02115 USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. EM jmeigs@partners.org OI Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institutes of Health [RO1 HL064753, RO1 HL076784, R01 AG028321]; National Center for Research Resources; General Clinical Research Centers Program [M01-RR-01066]; American Diabetes Association and National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140]; Earle Charlton Fund; Centre de Recherche Medicale de l'Universite de Sherbrooke; Canadian Institute of Health Research; GlaxoSmithKline FX The study was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195); the National Institutes of Health; National Center for Research Resources, National Institutes of Health grants RO1 HL064753, RO1 HL076784, and R01 AG028321 (EJB); General Clinical Research Centers Program (Grant No. M01-RR-01066); and a Career Development Award from the American Diabetes Association and National Institute of Diabetes and Digestive and Kidney Diseases K24 DK080140 (JBM). DMN is supported in part by the Earle Charlton Fund for Innovative Diabetes Research. MFH was supported by the Centre de Recherche Medicale de l'Universite de Sherbrooke and a Canadian Institute of Health Research Fellowships Health Professional Award. JBM currently has research grants from GlaxoSmithKline and sanofi-aventis, and has consulting agreements with Eli Lilly, Interleukin Genetics, Kalypsis, and Outcomes Science. NR 38 TC 12 Z9 15 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2010 VL 59 IS 4 BP 540 EP 546 DI 10.1016/j.metabol.2009.08.017 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 576ZO UT WOS:000276189200013 PM 19846171 ER PT J AU Baffy, G AF Baffy, Gyorgy TI Uncoupling protein-2 and cancer SO MITOCHONDRION LA English DT Review DE Cancer; Warburg effect; Metabolic reprogramming; Uncoupling protein-2; Oxidative stress; Chemoresistance ID MITOCHONDRIAL PROTON LEAK; BROWN-ADIPOSE-TISSUE; HYPOXIA-INDUCIBLE FACTOR-1; OXYGEN SPECIES PRODUCTION; LIPID-MOBILIZING FACTOR; BETA-CELL DYSFUNCTION; SKELETAL-MUSCLE UCP2; KAPPA-B ACTIVATION; OXIDATIVE STRESS; GENE-EXPRESSION AB Cancer cells respond to unfavorable microenvironments such as nutrient limitation, hypoxia, oxidative stress, and host defense by comprehensive metabolic reprogramming. Mitochondria are linked to this complex adaptive response and emerging evidence indicates that uncoupling protein-2 (UCP2), a mitochondria' inner membrane anion carrier, may contribute to this process. Effects of UCP2 on mitochondrial bioenergetics, redox homeostasis, and oxidant production in cancer cells may modulate molecular pathways of macromolecular biosynthesis, antioxidant defense, apoptosis, cell growth and proliferation, enhancing robustness and promoting chemoresistance. Elucidation of these interactions may identify novel anti-cancer strategies. Published by Elsevier B.V. on behalf of Mitochondria Research Society. C1 [Baffy, Gyorgy] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Baffy, Gyorgy] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Baffy, G (reprint author), 150 S Huntington Ave,Room A6-46, Boston, MA 02130 USA. EM gbaffy@partners.org NR 143 TC 56 Z9 59 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD APR PY 2010 VL 10 IS 3 BP 243 EP 252 DI 10.1016/j.mito.2009.12.143 PG 10 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 579AT UT WOS:000276339300001 PM 20005987 ER PT J AU Ji, ZY Flaherty, KT Tsao, H AF Ji, Zhenyu Flaherty, Keith T. Tsao, Hensin TI Molecular therapeutic approaches to melanoma SO MOLECULAR ASPECTS OF MEDICINE LA English DT Review DE Melanoma; Therapy; Molecular ID METASTATIC MALIGNANT-MELANOMA; RECOMBINANT INTERLEUKIN-2 THERAPY; INHIBITOR AZD6244 ARRY-142886; KIT PROTEIN EXPRESSION; ADVANCED SOLID TUMORS; MULTICENTER PHASE-II; STAGE IV MELANOMA; CUTANEOUS MELANOMA; CELL-LINES; B-RAF AB Metastatic melanoma is a highly lethal cancer that has historically been refractory to all tested pharmacological agents. An understanding of the mechanisms responsible for its oncogenesis is critical for developing successful therapies. An enormous amount of data generated over the last few decades have revealed important biological insights into melanoma initiation, progression and maintenance, which bring new directions and approaches to treatment of this devastating skin cancer. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Ji, Zhenyu; Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Flaherty, Keith T.; Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Bartlett 622,48 Blossom St,55 Fruit St, Boston, MA 02114 USA. EM htsao@partners.org FU American Cancer Society; National Institutes of Health; Massachusetts General Hospital FX We would like to thank the American Cancer Society (to H.T.), the National Institutes of Health (H.T.) and the generous donors at the Massachusetts General Hospital for their support. NR 125 TC 22 Z9 22 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0098-2997 EI 1872-9452 J9 MOL ASPECTS MED JI Mol. Asp. Med. PD APR PY 2010 VL 31 IS 2 SI SI BP 194 EP 204 DI 10.1016/j.mam.2010.02.004 PG 11 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 599NI UT WOS:000277919600006 PM 20176049 ER PT J AU Cirstea, D Hideshima, T Rodig, S Santo, L Pozzi, S Vallet, S Ikeda, H Perrone, G Gorgun, G Patel, K Desai, N Sportelli, P Kapoor, S Vali, S Mukherjee, S Munshi, NC Anderson, KC Raje, N AF Cirstea, Diana Hideshima, Teru Rodig, Scott Santo, Loredana Pozzi, Samantha Vallet, Sonia Ikeda, Hiroshi Perrone, Giulia Gorgun, Gullu Patel, Kishan Desai, Neil Sportelli, Peter Kapoor, Shweta Vali, Shireen Mukherjee, Siddhartha Munshi, Nikhil C. Anderson, Kenneth C. Raje, Noopur TI Dual Inhibition of Akt/Mammalian Target of Rapamycin Pathway by Nanoparticle Albumin-Bound-Rapamycin and Perifosine Induces Antitumor Activity in Multiple Myeloma SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID MAMMALIAN TARGET; IN-VIVO; THERAPEUTIC TARGETS; PARKINSONS-DISEASE; CANCER-THERAPY; TUMOR-CELLS; AKT KINASE; MTOR; ACTIVATION; APOPTOSIS AB The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway mediates multiple myeloma (MM) cell proliferation, survival, and development of drug resistance, underscoring the role of mTOR inhibitors, such as rapamycin, with potential anti-MM activity. However, recent data show a positive feedback loop from mTOR/S6K1 to Akt, whereby Akt activation confers resistance to mTOR inhibitors. We confirmed that suppression of mTOR signaling in MM cells by rapamycin was associated with upregulation of Akt phosphorylation. We hypothesized that inhibiting this positive feedback by a potent Akt inhibitor perifosine would augment rapamycin-induced cytotoxicity in MM cells. Perifosine inhibited rapamycin-induced phosphorylated Akt, resulting in enhanced cytotoxicity in MM.1S cells even in the presence of interleukin-6, insulin-like growth factor-I, or bone marrow stromal cells. Moreover, rapamycin-induced autophagy in MM.1S MM cells, as evidenced by electron microscopy and immunocytochemistry, was augmented by perifosine. Combination therapy increased apoptosis detected by Annexin V/propidium iodide analysis and caspase/poly(ADP-ribose) polymerase cleavage. Importantly, in vivo antitumor activity and prolongation of survival in a MM mouse xenograft model after treatment was enhanced with combination of nanoparticle albumin-bound-rapamycin and perifosine. Utilizing the in silico predictive analysis, we confirmed our experimental findings of this drug combination on PI3K, Akt, mTOR kinases, and the caspases. Our data suggest that mutual suppression of the PI3K/Akt/mTOR pathway by rapamycin and perifosine combination induces synergistic MM cell cytotoxicity, providing the rationale for clinical trials in patients with relapsed/refractory MM. Mol Cancer Ther; 9(4); 963-75. (C) 2010 AACR. C1 [Pozzi, Samantha; Vallet, Sonia; Patel, Kishan; Mukherjee, Siddhartha; Raje, Noopur] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. [Cirstea, Diana; Hideshima, Teru; Santo, Loredana; Ikeda, Hiroshi; Perrone, Giulia; Gorgun, Gullu; Munshi, Nikhil C.; Anderson, Kenneth C.; Raje, Noopur] Dana Farber Canc Inst, Leebow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Cirstea, Diana; Hideshima, Teru; Santo, Loredana; Ikeda, Hiroshi; Perrone, Giulia; Gorgun, Gullu; Munshi, Nikhil C.; Anderson, Kenneth C.; Raje, Noopur] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Rodig, Scott] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Desai, Neil] Abraxis Biosci LLC, Los Angeles, CA USA. [Sportelli, Peter] Keryx Biopharmaceut Inc, New York, NY USA. [Kapoor, Shweta; Vali, Shireen] Cellworks Grp Inc, Saratoga, CA USA. RP Raje, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, POB 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 FU AstraZeneca; ASCO CDA; LLS CDA; MMRF FX N. Raje has a research grant from AstraZeneca and is a consultant to Amgen, Celgene, and Novartis. No other potential conflicts of interest were disclosed.; Grant Support; ASCO CDA, LLS CDA, and MMRF (N. Raje). NR 38 TC 98 Z9 100 U1 2 U2 20 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD APR PY 2010 VL 9 IS 4 BP 963 EP 975 DI 10.1158/1535-7163.MCT-09-0763 PG 13 WC Oncology SC Oncology GA 607GP UT WOS:000278487400017 PM 20371718 ER PT J AU Kobayashi, T Inoue, T Shimizu, Y Terada, N Maeno, A Kajita, Y Yamasaki, T Kamba, T Toda, Y Mikami, Y Yamada, T Kamoto, T Ogawa, O Nakamura, E AF Kobayashi, Takashi Inoue, Takahiro Shimizu, Yosuke Terada, Naoki Maeno, Atsushi Kajita, Yoichiro Yamasaki, Toshinari Kamba, Tomomi Toda, Yoshinobu Mikami, Yoshiki Yamada, Tomomi Kamoto, Toshiyuki Ogawa, Osamu Nakamura, Eijiro TI Activation of Rac1 Is Closely Related to Androgen-Independent Cell Proliferation of Prostate Cancer Cells Both in Vitro and in Vivo SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; NF-KAPPA-B; RHO-GTPASES; RADICAL PROSTATECTOMY; PROGNOSTIC RELEVANCE; PRIMARY CULTURES; BINDING-PROTEIN; LNCAP CELLS; S6 KINASE; RECEPTOR AB We and others previously showed that signaling through cSrc or atypical protein kinase C (aPKC) pathway regulates the proliferation of prostate cancer cells and is associated with their progression to castrate-resistance in vivo. However, the interrelation of these two kinases has been largely unexplored. In the present study, we show that androgen-induced activation of cSrc regulates the activity of aPKC through the small molecular weight G protein Rac1 in androgen-dependent LNCaP cells. Knockdown of cSrc in those cells reduces the phosphorylation of aPKC and the abundance of activated form of Rac1. Additionally, the treatment of those cells with Rac1 inhibitor repressed cell cycle progression at G(1)/S transition. In fact, forced expression of a constitutively active Rac1 mutant in LNCaP cells promoted cell proliferation under androgen-depleted conditions both in vitro and in vivo. Moreover, LNCaP C4-2 and AILNCaP cells, the syngeneic androgen-independent sublines from LNCaP cells, harbored abundant Rac1-GTP. Importantly, the inhibition of Rac1 suppressed cell proliferation and induced apoptotic cell death in all prostate cancer cell lines tested irrespective of their androgen-dependence. In immunohistochemical evaluation of tumor specimens from prostate cancer patients, Rac1 pathway appeared to be activated in the majority of castrate-resistant diseases. Collectively, our present results both in vitro and in vivo highly implicate that Rac1 can be a potential therapeutic target for patients with advanced prostate cancer, especially those with castrate-resistant status. (Molecular Endocrinology 24: 722-734, 2010) C1 [Nakamura, Eijiro] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kobayashi, Takashi; Inoue, Takahiro; Shimizu, Yosuke; Terada, Naoki; Maeno, Atsushi; Kajita, Yoichiro; Yamasaki, Toshinari; Kamba, Tomomi; Ogawa, Osamu; Nakamura, Eijiro] Kyoto Univ, Grad Sch Med, Dept Urol, Kyoto 6068507, Japan. [Mikami, Yoshiki] Kyoto Univ Hosp, Anat Pathol Lab, Kyoto 6068507, Japan. [Toda, Yoshinobu] Kyoto Univ, Grad Sch Med, Anat Ctr, Kyoto 6068501, Japan. [Yamada, Tomomi] Mie Univ, Grad Sch Med, Dept Translat Med Sci, Tsu, Mie 5148507, Japan. RP Nakamura, E (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 457, Boston, MA 02115 USA. EM nakamura_eijiro@dfci.harvard.edu FU Ministry of Education, Culture, Sports, Science, and Technology of Japan; Yamaguchi Endocrine Research Association; Japanese Foundation for Prostate Research; Organon Urology Academia; Japanese Urological Association; Kobayashi Institute for Innovative Cancer Chemotherapy; Takeda Science Foundation; Ministry of Education, Culture, Sports, Science, and Technology, Japan FX This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Yamaguchi Endocrine Research Association, the Japanese Foundation for Prostate Research, the Organon Urology Academia, the First Young Research Grant from Japanese Urological Association, the Kobayashi Institute for Innovative Cancer Chemotherapy, the Takeda Science Foundation, and the Formation for Genomic Analysis of Disease Model Animals with Multiple Genetic (Center of Excellence Program), Ministry of Education, Culture, Sports, Science, and Technology, Japan. T. Ko. is a Japan Society for the Promotion of Science Research Fellow. NR 59 TC 18 Z9 21 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD APR PY 2010 VL 24 IS 4 BP 722 EP 734 DI 10.1210/me.2009-0326 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 575FC UT WOS:000276051300004 PM 20203103 ER PT J AU Yadav, V Marracci, GH Munar, MY Cherala, G Stuber, LE Alvarez, L Shinto, L Koop, DR Bourdette, DN AF Yadav, Vijayshree Marracci, Gail H. Munar, Myrna Y. Cherala, Ganesh Stuber, Lauren E. Alvarez, Lilia Shinto, Lynne Koop, Dennis R. Bourdette, Dennis N. TI Pharmacokinetic study of lipoic acid in multiple sclerosis: comparing mice and human pharmacokinetic parameters SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE Multiple sclerosis; lipoic acid; pharmacokinetics; experimental autoimmune encephalomyelitis; anti-oxidants; dietary supplements ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PLACEBO-CONTROLLED TRIAL; SYMPTOMATIC DIABETIC POLYNEUROPATHY; STIMULATES CAMP PRODUCTION; BURNING MOUTH SYNDROME; CONTROLLED PHASE IIB; T-CELL MIGRATION; DOUBLE-BLIND; THIOCTIC ACID; HEALTHY-VOLUNTEERS AB Lipoic acid is a natural anti-oxidant available as an oral supplement from a number of different manufacturers. Lipoic acid administered subcutaneously is an effective therapy for murine experimental autoimmune encephalomyelitis, a model of multiple sclerosis. The aim of this study was to compare serum lipoic acid levels with oral dosing in patients with multiple sclerosis with serum levels in mice receiving subcutaneous doses of lipoic acid. We performed serum pharmacokinetic studies in patients with multiple sclerosis after a single oral dose of 1200 mg lipoic acid. Patients received one of the three different racemic formulations randomly: tablet (Formulation A) and capsules (Formulations B and C). Mice pharmacokinetic studies were performed with three different subcutaneous doses (20, 50 and 100 mg/kg racemic lipoic acid). The pharmacokinetic parameters included Maximum Serum Concentrations (C(max) in mu g/ml) and area under the curve (0-infinity) (AUC(0-infinity) in mu g*min/ml). We found mean C(max) and AUC(0-infinity) in patients with multiple sclerosis as follows: group A (N=7) 3.8 +/- 2.6 and 443.1 +/- 283.9; group B (N=8) 9.9 +/- 4.5 and 745.2 +/- 308.7 and group C (N=8) 10.3 +/- 3.8 and 848.8 +/- 360.5, respectively. Mean C(max) and AUC(0-infinity) in the mice were: 100 mg/kg lipoic acid: 30.9 +/- 2.9 and 998 +/- 245; 50 mg/kg lipoic acid: 7.6 +/- 1.4 and 223 +/- 20; 20 mg/kg lipoic acid: 2.7 +/- 0.7 and 119 +/- 33. We conclude that patients taking 1200 mg of lipoic acid from two of the three oral formulations achieved serum C(max) and AUC levels comparable to that observed in mice receiving 50 mg/kg subcutaneous dose of lipoic acid, which is a highly therapeutic dose in experimental autoimmune encephalomyelitis. A dose of 1200 mg oral lipoic acid can achieve therapeutic serum levels in patients with multiple sclerosis. C1 [Yadav, Vijayshree; Marracci, Gail H.; Stuber, Lauren E.; Alvarez, Lilia; Shinto, Lynne; Bourdette, Dennis N.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Marracci, Gail H.; Bourdette, Dennis N.] Portland VA Med Ctr, Portland, OR USA. [Koop, Dennis R.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Munar, Myrna Y.; Cherala, Ganesh] Oregon Hlth & Sci Univ, Oregon State Univ, Portland, OR 97239 USA. RP Yadav, V (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Mail Code L 226,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM yadavv@ohsu.edu FU National Center of Complementary and Alternative medicine, Oregon Clinical and Translational Research Institute (OCTRI) [K23 AT003258]; National Center for Research Resources (NCRR) [UL1 RR024140]; National Institutes of Health (NIH); Biomedical Laboratory Research & Development Service, Department of Veterans Affairs; Laura Fund for Innovation in MS Research; Nancy Davis Center Without Walls FX Grant number K23 AT003258 from National Center of Complementary and Alternative medicine, Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1 RR024140 from the National Center for Research Resources (NCRR), components of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research, and the Biomedical Laboratory Research & Development Service, Department of Veterans Affairs, the Laura Fund for Innovation in MS Research and the Nancy Davis Center Without Walls. We thank Pure Encapsulations (R) and Vital Nutrients (R) for donating their LA formulation products. NR 49 TC 14 Z9 15 U1 1 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD APR PY 2010 VL 16 IS 4 BP 387 EP 397 DI 10.1177/1352458509359722 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 581NI UT WOS:000276530000002 PM 20150394 ER PT J AU Martinez-Boubeta, C Balcells, L Cristofol, R Sanfeliu, C Rodriguez, E Weissleder, R Lope-Piedrafita, S Simeonidis, K Angelakeris, M Sandiumenge, F Calleja, A Casas, L Monty, C Martinez, B AF Martinez-Boubeta, Carlos Balcells, Lluis Cristofol, Rosa Sanfeliu, Coral Rodriguez, Elisenda Weissleder, Ralph Lope-Piedrafita, Silvia Simeonidis, Konstantinos Angelakeris, Makis Sandiumenge, Felip Calleja, Alberto Casas, Lluis Monty, Claude Martinez, Benjamin TI Self-assembled multifunctional Fe/MgO nanospheres for magnetic resonance imaging and hyperthermia SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Core-shell; Hyperthermia; Magnetism; MRI; Nanoparticles; Vapor condensation ID NANOPARTICLES; OXIDE; NANOCRYSTALS; PARTICLES; MOSSBAUER; SYSTEM; MORPHOLOGY; EXCRETION; TISSUE; TUMORS AB A one-step process for the production of nanoparticles presenting advanced magnetic properties can be achieved using vapor condensation. In this article, we report on the fabrication of Fe particles covered by a uniform MgO epitaxial shell. MgO has a lower surface energy than Fe, which results in a core-shell crystal formation. The particles satisfy a few of technical requirements for the practical use in real clinics, such as a high biocompatibility in living cells in-vitro, an injection through blood vessels without any clothing problems in murine model, a high absorption rate for magnetic hyperthermia at small particle concentration, and the potential to be used as contrast agent in the field of diagnostic magnetic imaging. They are also able to be used in drug delivery and magnetic-activated cell sorting. From the Clinical Editor: In this paper, the authors report on the synthesis of Fe particles covered by a uniform MgO epitaxial shell resulting in a core-shell crystal formation. The particles are proven to be useful as contrast agents for magnetic resonance imaging and have the potential to be useful as heating mediators for cancer therapy through hyperthermia. They also might be used in drug delivery and magnetic-activated cell sorting. (C) 2010 Elsevier Inc. All rights reserved. C1 [Martinez-Boubeta, Carlos] Univ Barcelona, Dept Elect, IN2UB, E-08028 Barcelona, Spain. [Martinez-Boubeta, Carlos; Balcells, Lluis; Sandiumenge, Felip; Calleja, Alberto; Martinez, Benjamin] ICMAB CSIC, Bellaterra, Spain. [Cristofol, Rosa; Sanfeliu, Coral] CSIC IDIBAPS, IIBB, Barcelona, Spain. [Rodriguez, Elisenda; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Lope-Piedrafita, Silvia] Univ Autonoma Barcelona, Serv Resonancia Magnet Nucl, Bellaterra, Spain. [Simeonidis, Konstantinos; Angelakeris, Makis] Aristotle Univ Thessaloniki, Dept Phys, GR-54006 Thessaloniki, Greece. [Calleja, Alberto] UAB, Inst Ciencia & Tecnol Ambientals, Bellaterra, Spain. [Casas, Lluis] UAB, Unitat Cristal Log & Mineral, Dept Geol, Bellaterra, Spain. [Monty, Claude] CNRS Procedes Mat & Energie Solaire, Font Romeu, France. RP Martinez-Boubeta, C (reprint author), Univ Barcelona, Dept Elect, IN2UB, Marti & Franques 1, E-08028 Barcelona, Spain. EM cboubeta@el.ub.es RI Sandiumenge, Felip/C-2743-2012; Calleja, Alberto/B-2248-2008; MARTINEZ, BENJAMIN/A-1625-2008; Lope-Piedrafita, Silvia/I-4808-2012; Martinez Boubeta, Carlos/G-9298-2014; Casas, Lluis/L-1242-2014; Simeonidis, Konstantinos/A-5450-2015; Balcells, Lluis/B-5027-2013; Angelakeris, Mavroidis/I-2419-2015 OI Sandiumenge, Felip/0000-0003-1336-1529; MARTINEZ, BENJAMIN/0000-0001-9879-7748; Martinez Boubeta, Carlos/0000-0001-7665-0649; Casas, Lluis/0000-0003-0948-8658; Simeonidis, Konstantinos/0000-0001-9804-4690; Balcells, Lluis/0000-0001-6603-7357; FU Spanish MEC [MAT2006-13572-C02-01, SAF2006-13092-C02-02]; CONSOLIDER [CSD2007-00041]; ISCIII [RD06/0013/1004]; FEDER; Generalitat de Catalunya [2005SGR-00509]; EC [39693] FX This work was supported by the Spanish MEC (MAT2006-13572-C02-01 and SAF2006-13092-C02-02), CONSOLIDER (CSD2007-00041), ISCIII (RD06/0013/1004), FEDER program and Generalitat de Catalunya (2005SGR-00509). This work was partially funded by EC project SOLFACE in the frame of the 6ePCRDT program. C. M-B. thanks the Spanish MEC for financial support through the Juan de la Cierva & Ramon y Cajal programs. E. R. kindly acknowledges the EC-Marie Curie grant OIF (Molecular Imaging 39693). NR 44 TC 31 Z9 32 U1 3 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD APR PY 2010 VL 6 IS 2 BP 362 EP 370 DI 10.1016/j.nano.2009.09.003 PG 9 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 575TG UT WOS:000276090600017 PM 19800988 ER PT J AU Ji, HK Liu, XS AF Ji, Hongkai Liu, X. Shirley TI Analyzing 'omics data using hierarchical models SO NATURE BIOTECHNOLOGY LA English DT Article C1 [Ji, Hongkai] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Ji, HK (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. EM hji@jhsph.edu; xsliu@jimmy.harvard.edu FU NHGRI NIH HHS [R01 HG004069, R01 HG004069-04] NR 10 TC 23 Z9 24 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2010 VL 28 IS 4 BP 337 EP 340 DI 10.1038/nbt.1619 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 580PW UT WOS:000276462400020 PM 20379180 ER PT J AU Anitei, M Stange, C Parshina, I Baust, T Schenck, A Raposo, G Kirchhausen, T Hoflack, B AF Anitei, Mihaela Stange, Christoph Parshina, Irina Baust, Thorsten Schenck, Annette Raposo, Graca Kirchhausen, Tomas Hoflack, Bernard TI Protein complexes containing CYFIP/Sra/PIR121 coordinate Arf1 and Rac1 signalling during clathrin-AP-1-coated carrier biogenesis at the TGN SO NATURE CELL BIOLOGY LA English DT Article ID TRANS-GOLGI NETWORK; CLATHRIN-MEDIATED ENDOCYTOSIS; LINKED MENTAL-RETARDATION; MANNOSE 6-PHOSPHATE RECEPTORS; ACTIN DYNAMICS; ARP2/3 COMPLEX; AMPA RECEPTORS; NEURONAL CONNECTIVITY; VESICLE FORMATION; PLASMA-MEMBRANE AB Actin dynamics is a tightly regulated process involved in various cellular events including biogenesis of clathrin-coated, AP-1 (adaptor protein 1)-coated transport carriers connecting the trans-Golgi network (TGN) and the endocytic pathway. However, the mechanisms coordinating coat assembly, membrane and actin remodelling during post-TGN transport remain poorly understood. Here we show that the Arf1 (ADP-ribosylation factor 1) GTPase synchronizes the TGN association of clathrin-AP-1 coats and protein complexes comprising CYFIP (cytoplasmic fragile-X mental retardation interacting protein; Sra, PIR121), a clathrin heavy chain binding protein associated with mental retardation. The Rac1 GTPase and its exchange factor beta-PIX (PAK-interacting exchange factor) activate these complexes, allowing N-WASP-dependent and Arp2/3-dependent actin polymerization towards membranes, thus promoting tubule formation. These phenomena can be recapitulated with synthetic membranes. This protein-network-based mechanism facilitates the sequential coordination of Arf1-dependent membrane priming, through the recruitment of coats and CYFIP-containing complexes, and of Rac1-dependent actin polymerization, and provides complementary but independent levels of regulation during early stages of clathrin-AP1-coated carrier biogenesis. C1 [Anitei, Mihaela; Stange, Christoph; Parshina, Irina; Baust, Thorsten; Hoflack, Bernard] Tech Univ Dresden, Ctr Biotechnol, D-01307 Dresden, Germany. [Baust, Thorsten; Kirchhausen, Tomas] Harvard Univ, Sch Med, CBRI, Boston, MA 02115 USA. [Schenck, Annette] Nijmegen Ctr Mol Life Sci, Donders Inst Brain Cognit & Behav, NL-6525 GA Nijmegen, Netherlands. [Schenck, Annette] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 GA Nijmegen, Netherlands. [Raposo, Graca] Inst Curie, Ctr Rech, F-75231 Paris, France. [Raposo, Graca] CNRS, UMR144, F-75700 Paris, France. [Raposo, Graca] IBiSA, Cell & Tissue Imaging Facil, F-75248 Paris, France. RP Hoflack, B (reprint author), Tech Univ Dresden, Ctr Biotechnol, Tatzberg 47-51, D-01307 Dresden, Germany. EM bernard.hoflack@biotec.tu-dresden.de RI Schenck, Annette/E-4514-2012; Anitei, Mihaela/A-2541-2015 OI Schenck, Annette/0000-0002-6918-3314; Anitei, Mihaela/0000-0002-3156-7195 FU NIGMS NIH HHS [GM075252, R01 GM075252, R01 GM075252-04] NR 63 TC 57 Z9 57 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2010 VL 12 IS 4 BP 330 EP U65 DI 10.1038/ncb2034 PG 23 WC Cell Biology SC Cell Biology GA 577BI UT WOS:000276194600006 PM 20228810 ER PT J AU McGovern, DPB Gardet, A Torkvist, L Goyette, P Essers, J Taylor, KD Neale, BM Ong, RTH Lagace, C Li, C Green, T Stevens, CR Beauchamp, C Fleshner, PR Carlson, M D'Amato, M Halfvarson, J Hibberd, ML Lordal, M Padyukov, L Andriulli, A Colombo, E Latiano, A Palmieri, O Bernard, EJ Deslandres, C Hommes, DW de Jong, DJ Stokkers, PC Weersma, RK Sharma, Y Silverberg, MS Cho, JH Wu, J Roeder, K Brant, SR Schumm, LP Duerr, RH Dubinsky, MC Glazer, NL Haritunians, T Ippoliti, A Melmed, GY Siscovick, DS Vasiliauskas, EA Targan, SR Annese, V Wijmenga, C Pettersson, S Rotter, JI Xavier, RJ Daly, MJ Rioux, JD Seielstad, M AF McGovern, Dermot P. B. Gardet, Agnes Torkvist, Leif Goyette, Philippe Essers, Jonah Taylor, Kent D. Neale, Benjamin M. Ong, Rick T. H. Lagace, Caroline Li, Chun Green, Todd Stevens, Christine R. Beauchamp, Claudine Fleshner, Phillip R. Carlson, Marie D'Amato, Mauro Halfvarson, Jonas Hibberd, Martin L. Lordal, Mikael Padyukov, Leonid Andriulli, Angelo Colombo, Elisabetta Latiano, Anna Palmieri, Orazio Bernard, Edmond-Jean Deslandres, Colette Hommes, Daan W. de Jong, Dirk J. Stokkers, Pieter C. Weersma, Rinse K. Sharma, Yashoda Silverberg, Mark S. Cho, Judy H. Wu, Jing Roeder, Kathryn Brant, Steven R. Schumm, L. Phillip Duerr, Richard H. Dubinsky, Marla C. Glazer, Nicole L. Haritunians, Talin Ippoliti, Andy Melmed, Gil Y. Siscovick, David S. Vasiliauskas, Eric A. Targan, Stephan R. Annese, Vito Wijmenga, Cisca Pettersson, Sven Rotter, Jerome I. Xavier, Ramnik J. Daly, Mark J. Rioux, John D. Seielstad, Mark CA NIDDK IBD Genetics Consortium TI Genome-wide association identifies multiple ulcerative colitis susceptibility loci SO NATURE GENETICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; RETICULUM STRESS-RESPONSE; CROHNS-DISEASE; GENETIC-VARIANTS; RISK; POPULATION; CONTRIBUTE; IMMUNITY AB Ulcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation underlying ulcerative colitis risk, we present two distinct genome-wide association studies of ulcerative colitis and their joint analysis with a previously published scan(1), comprising, in aggregate, 2,693 individuals with ulcerative colitis and 6,791 control subjects. Fifty-nine SNPs from 14 independent loci attained an association significance of P < 10(-5). Seven of these loci exceeded genome-wide significance (P < 5 x 10(-8)). After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were significantly associated with ulcerative colitis (P < 5 x 10(-8)), including the immunoglobulin receptor gene FCGR2A, 5p15, 2p16 and ORMDL3 (orosomucoid1-like 3). We confirmed association with 14 previously identified ulcerative colitis susceptibility loci, and an analysis of acknowledged Crohn's disease loci showed that roughly half of the known Crohn's disease associations are shared with ulcerative colitis. These data implicate approximately 30 loci in ulcerative colitis, thereby providing insight into disease pathogenesis. C1 [McGovern, Dermot P. B.; Fleshner, Phillip R.; Dubinsky, Marla C.; Ippoliti, Andy; Melmed, Gil Y.; Vasiliauskas, Eric A.; Targan, Stephan R.] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA. [Gardet, Agnes; Li, Chun; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Gardet, Agnes; Li, Chun; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. [Torkvist, Leif] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Torkvist, Leif; Lordal, Mikael] Karolinska Univ Hosp, IBD Clin Res Grp, Stockholm, Sweden. [Goyette, Philippe; Lagace, Caroline; Beauchamp, Claudine; Rioux, John D.] Univ Montreal, Montreal, PQ, Canada. [Goyette, Philippe; Lagace, Caroline; Beauchamp, Claudine; Rioux, John D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Essers, Jonah; Neale, Benjamin M.; Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Taylor, Kent D.; Haritunians, Talin; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Ong, Rick T. H.; Seielstad, Mark] Genome Inst Singapore, Singapore, Singapore. [Green, Todd; Stevens, Christine R.; Xavier, Ramnik J.; Daly, Mark J.] MIT & Harvard, Broad Inst, Cambridge, MA USA. [Carlson, Marie] Univ Uppsala Hosp, Dept Med Sci, Gastroenterol Res Grp, Uppsala, Sweden. [D'Amato, Mauro] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden. [Halfvarson, Jonas] Orebro Univ Hosp, Dept Internal Med, Div Gastroenterol, Orebro, Sweden. [Hibberd, Martin L.] Genome Inst Singapore, Singapore, Singapore. [Lordal, Mikael] Karolinska Univ Hosp, Dept Med, Stockholm, Sweden. [Padyukov, Leonid] Karolinska Univ Hosp Solna, Rheumatol Unit, Dept Med, Karolinska Inst, Stockholm, Sweden. [Andriulli, Angelo; Colombo, Elisabetta; Latiano, Anna; Palmieri, Orazio; Annese, Vito] Osped Casa Sollievo Sofferenza, Ist Ricovero & Cura Carattere Sci, San Giovanni Rotondo, Italy. [Bernard, Edmond-Jean] Univ Montreal, Ctr Hosp Univ, Montreal, PQ, Canada. [Deslandres, Colette] Hop St Justine, Dept Gastroenterol, Montreal, PQ H3T 1C5, Canada. [Hommes, Daan W.] Leiden Univ, Dept Gastroenterol & Hepatol, Med Ctr, Leiden, Netherlands. [de Jong, Dirk J.] Radboud Univ Nijmegen, Dept Gastroenterol & Hepatol, NL-6525 ED Nijmegen, Netherlands. [Stokkers, Pieter C.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands. [Weersma, Rinse K.] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands. [NIDDK IBD Genetics Consortium] Yale Univ, NIDDK, New Haven, CT USA. [Sharma, Yashoda; Cho, Judy H.] Yale Univ, Dept Med, Sect Digest Dis, New Haven, CT 06520 USA. [Silverberg, Mark S.] Univ Toronto, Mt Sinai Hosp, Ctr Inflammatory Bowel Dis, Toronto, ON M5G 1X5, Canada. [Cho, Judy H.] Yale Univ, Dept Genet, New Haven, CT USA. [Wu, Jing] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Roeder, Kathryn; Brant, Steven R.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Roeder, Kathryn; Brant, Steven R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Schumm, L. Phillip] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Duerr, Richard H.] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Glazer, Nicole L.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Glazer, Nicole L.; Siscovick, David S.] Univ Washington, Dept Gen Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Wijmenga, Cisca] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands. [Pettersson, Sven] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Pettersson, Sven] Singapore Gen Hosp, Lab Inflammat Biol, Singapore 0316, Singapore. [Seielstad, Mark] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. RP McGovern, DPB (reprint author), Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA. EM mcgovernd@cshs.org; john.david.rioux@umontreal.ca; mark.seielstad@ucsf.edu RI D'Amato, Mauro/F-2450-2010; Hibberd, Martin/D-5050-2009; Silverberg, Mark/B-4183-2008; Wijmenga, Cisca/D-2173-2009; Rioux, John/A-9599-2015; Jong, D.J./L-4417-2015; Palmieri, Orazio/J-7697-2012; Latiano, Anna/R-1965-2016; Andriulli, Angelo/B-5027-2017; OI Wijmenga, Cisca/0000-0002-5635-1614; D'Amato, Mauro/0000-0003-2743-5197; Rioux, John/0000-0001-7560-8326; Palmieri, Orazio/0000-0002-0019-7929; Latiano, Anna/0000-0003-3719-2061; Andriulli, Angelo/0000-0001-8862-7083; Seielstad, Mark/0000-0001-5783-1401; Duerr, Richard/0000-0001-6586-3905; Hibberd, Martin/0000-0001-8587-1849; Halfvarson, Jonas/0000-0003-0122-7234; Padyukov, Leonid/0000-0003-2950-5670 FU US National Center for Research Resources (NCRR) [M01-RR00425]; US National Institutes of Health/NIDDK [P01-DK046763, DK83756, DK086502, DK043351, DK062431, DK062422, DK062420, DK062432, DK062423, DK062413, DK062429]; Diabetes Endocrinology Research Center [DK063491]; Cedars-Sinai Medical Center; US National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL087652]; US National Institute of Neurological Disorders and Stroke; Crohn's and Colitis Foundation of America; Bohmfalk Funds for Medical Research; Burroughs Wellcome Medical Foundation; US National Institute of Allergy and Infectious Diseases [AI065687, AI067152]; US National Institute of Diabetes and Digestive and Kidney Diseases [DK064869]; Swedish Society of Medicine; Bengt Ihre Foundation; Karolinska Institutet; Swedish National Program for IBD Genetics; Swedish Organization for IBD; Swedish Medical Research Council; Soderbergh Foundation; Swedish Cancer Foundation; [DK76984]; [DK084554] FX This study was supported in part by US National Center for Research Resources (NCRR) grant M01-RR00425 to the Cedars-Sinai General Research Center Genotyping core; US National Institutes of Health/NIDDK grant P01-DK046763; Diabetes Endocrinology Research Center grant DK063491; Cedars-Sinai Medical Center Inflammatory Bowel Disease Research Funds. Additional funding was provided by grants DK76984 (M. C. D.) and DK084554 (M. C. D. and D. P. B. M.). Cardiovascular Health Study research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150 and N01-HC-45133; grant numbers U01 HL080295 and R01 HL087652 from the US National Heart, Lung, and Blood Institute; and additional contribution from the US National Institute of Neurological Disorders and Stroke. A full list of principal Cardiovascular Health Study investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. A. G. is supported by the Crohn's and Colitis Foundation of America. R.J.X. and M.J.D. are supported by grants DK83756, DK086502 and DK043351 (NIDDK).; The NIDDK IBD Genetics Consortium is funded by the following grants: DK062431 (S. R. B.), DK062422 (J.H.C.), DK062420 (R. H. D.), DK062432 (J.D.R.), DK062423 (M. S. S.), DK062413 (D. P. B. M.) and DK062429 (J.H.C.). J.H.C. is also funded by Bohmfalk Funds for Medical Research, Burroughs Wellcome Medical Foundation and the Crohn's and Colitis Foundation of America. J.D.R. is also funded by grants from the US National Institute of Allergy and Infectious Diseases (AI065687; AI067152) and from the US National Institute of Diabetes and Digestive and Kidney Diseases (DK064869).; Activities in Sweden were supported by the Swedish Society of Medicine, the Bengt Ihre Foundation, the Karolinska Institutet, the Swedish National Program for IBD Genetics, the Swedish Organization for IBD, the Swedish Medical Research Council, the Soderbergh Foundation and the Swedish Cancer Foundation. Support for genotyping and genetic data analysis was provided by the Singapore National Cancer Centre, Singapore General Hospital and the Singapore Millennium Foundation (to S. P.) and the Agency for Science Technology and Research (A*STAR), Singapore (to M. L. H. and M. S.). Genotyping and DNA handling at the Genome Institute of Singapore were performed by W.Y. Meah, K. K. Heng, H. B. Toh, X. Lin, S. Rajaram, D. Tan and C. H. Wong. We are grateful to the funders and investigators of the Epidemiological Investigation of Rheumatoid Arthritis for providing genotype data from healthy Swedish individuals. NR 27 TC 320 Z9 328 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2010 VL 42 IS 4 BP 332 EP U88 DI 10.1038/ng.549 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 576NE UT WOS:000276150500013 PM 20228799 ER PT J AU Van Vlierberghe, P Palomero, T Khiabanian, H Van der Meulen, J Castillo, M Van Roy, N De Moerloose, B Philippe, J Gonzalez-Garcia, S Toribio, ML Taghon, T Zuurbier, L Cauwelier, B Harrison, CJ Schwab, C Pisecker, M Strehl, S Langerak, AW Gecz, J Sonneveld, E Pieters, R Paietta, E Rowe, JM Wiernik, PH Benoit, Y Soulier, J Poppe, B Yao, XP Cordon-Cardo, C Meijerink, J Rabadan, R Speleman, F Ferrando, A AF Van Vlierberghe, Pieter Palomero, Teresa Khiabanian, Hossein Van der Meulen, Joni Castillo, Mireia Van Roy, Nadine De Moerloose, Barbara Philippe, Jan Gonzalez-Garcia, Sara Toribio, Maria L. Taghon, Tom Zuurbier, Linda Cauwelier, Barbara Harrison, Christine J. Schwab, Claire Pisecker, Markus Strehl, Sabine Langerak, Anton W. Gecz, Jozef Sonneveld, Edwin Pieters, Rob Paietta, Elisabeth Rowe, Jacob M. Wiernik, Peter H. Benoit, Yves Soulier, Jean Poppe, Bruce Yao, Xiaopan Cordon-Cardo, Carlos Meijerink, Jules Rabadan, Raul Speleman, Frank Ferrando, Adolfo TI PHF6 mutations in T-cell acute lymphoblastic leukemia SO NATURE GENETICS LA English DT Article ID FORSSMAN-LEHMANN-SYNDROME; X-INACTIVATION PROFILE; GENE-EXPRESSION; LINKED GENE; CHROMOSOME; FEMALES; PROTEIN AB Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer(1,2). T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males(3). In this study, we report the identification of inactivating mutations and deletions in the X-linked plant homeodomain finger 6 (PHF6) gene in 16% of pediatric and 38% of adult primary T-ALL samples. Notably, PHF6 mutations are almost exclusively found in T-ALL samples from male subjects. Mutational loss of PHF6 is importantly associated with leukemias driven by aberrant expression of the homeobox transcription factor oncogenes TLX1 and TLX3. Overall, these results identify PHF6 as a new X-linked tumor suppressor in T-ALL and point to a strong genetic interaction between PHF6 loss and aberrant expression of TLX transcription factors in the pathogenesis of this disease. C1 [Van Vlierberghe, Pieter; Palomero, Teresa; Ferrando, Adolfo] Columbia Univ, Inst Canc Genet, Med Ctr, New York, NY 10027 USA. [Van Vlierberghe, Pieter; Van der Meulen, Joni; Van Roy, Nadine; Poppe, Bruce; Speleman, Frank] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. [Van Vlierberghe, Pieter; Zuurbier, Linda; Pieters, Rob; Meijerink, Jules] Erasmus MC, Dept Pediat Oncol Hematol, Rotterdam, Netherlands. [Palomero, Teresa; Castillo, Mireia; Cordon-Cardo, Carlos; Ferrando, Adolfo] Columbia Univ, Dept Pathol, Med Ctr, New York, NY USA. [Khiabanian, Hossein; Rabadan, Raul] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY USA. [De Moerloose, Barbara; Benoit, Yves] Ghent Univ Hosp, Dept Pediat Hemato Oncol, B-9000 Ghent, Belgium. [Philippe, Jan; Taghon, Tom] Ghent Univ Hosp, Dept Clin Chem Immunol & Microbiol, B-9000 Ghent, Belgium. [Gonzalez-Garcia, Sara; Toribio, Maria L.] UAM, CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain. [Cauwelier, Barbara] Hosp St Jan, Dept Hematol, Brugge, Belgium. [Harrison, Christine J.; Schwab, Claire] Newcastle Univ, Leukaemia Res Cytogenet Grp, No Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Pisecker, Markus; Strehl, Sabine] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria. [Langerak, Anton W.] Erasmus MC, Dept Immunol, Rotterdam, Netherlands. [Gecz, Jozef] Univ Adelaide, Dept Genet & Mol Pathol, Adelaide, SA, Australia. [Gecz, Jozef] Univ Adelaide, Dept Pediat, Adelaide, SA, Australia. [Sonneveld, Edwin; Pieters, Rob] DCOG, The Hague, Netherlands. [Paietta, Elisabeth; Wiernik, Peter H.] Montefiore Med Ctr N, Bronx, NY USA. [Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel. [Rowe, Jacob M.] Technion Israel Inst Technol, Haifa, Israel. [Soulier, Jean] Hop St Louis, APHP, INSERM, Hematol Lab,U944, Paris, France. [Yao, Xiaopan] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ferrando, Adolfo] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. RP Ferrando, A (reprint author), Columbia Univ, Inst Canc Genet, Med Ctr, New York, NY 10027 USA. EM af2196@columbia.edu RI Ferrando, Adolfo /Q-7026-2016; Toribio, Maria L/C-2039-2017; Philippe, Jan/A-1027-2008; Van Vlierberghe, Pieter/G-8894-2013; Castillo-Martin, Mireia/H-6152-2013 OI Toribio, Maria L/0000-0002-8637-0373; Khiabanian, Hossein/0000-0003-1446-4394; Strehl, Sabine/0000-0002-0179-0628; Meijerink, Jules/0000-0002-6860-798X; Gecz, Jozef/0000-0002-7884-6861; Philippe, Jan/0000-0003-4857-5746; Van Vlierberghe, Pieter/0000-0001-9063-7205; FU Fund for Scientific Research (FWO) Flanders [G.0198.08, G.0869.10N]; GOA-UGent [12051203]; IWT-Vlaanderen [060848]; Children Cancer Fund Ghent; Leukemia Research UK; Stichting Kinderen Kankervrij [KiKa 2007-012]; Belgian Program of Interuniversity Poles of Attraction; Belgian Foundation against Cancer; Austrian Ministry of Science and Research [GZ 200.136/1-VI/1/2005]; US National Library of Medicine [1R01LM010140-01]; ECOG tumor bank; DCOG tumor bank; Spain's Plan Nacional [BFU 2007-60990, PlanE2009-0110]; Comunidad de Madrid [S-SAL0304-2006]; Fundacion MM [RECAVA RD06/0014/1012]; Fundacion Ramon Areces; Alex's Lemonade Stand Foundation; US Northeast Biodefense Center [U54-AI057158]; US National Institutes of Health [R01CA120196, R01CA129382]; Rally across America Foundation; Swim across America Foundation; Golfers against Cancer Foundation; Leukemia and Lymphoma Society FX This study was supported by the Fund for Scientific Research (FWO) Flanders (postdoctoral grants to P. V. V. and T. T., PhD grant to J.V.d.M., senior clinical investigator award to B. P. and project grants G.0198.08 and G.0869.10N to F. S.); the GOA-UGent (grant no. 12051203); the IWT-Vlaanderen (SBO grant no. 060848); the Children Cancer Fund Ghent (F. S.); Leukemia Research UK (C.J.H.); the Stichting Kinderen Kankervrij (KiKa; grant no. KiKa 2007-012 to L.Z.); the Belgian Program of Interuniversity Poles of Attraction; the Belgian Foundation against Cancer; the Austrian Ministry of Science and Research (GEN-AU Child, GZ 200.136/1-VI/1/2005 to S. S.), the US National Library of Medicine (1R01LM010140-01 to R. R. and H. K.); the ECOG and DCOG tumor banks; grants from Spain's Plan Nacional (BFU 2007-60990 and PlanE2009-0110 to M. L. T.), Comunidad de Madrid (S-SAL0304-2006 to M. L. T.), Fundacion MM (M. L. T.), Instituto de Salud Carlos III (RECAVA RD06/0014/1012 to M. L. T.), an Institutional Grant from the Fundacion Ramon Areces (M. L. T.), the Alex's Lemonade Stand Foundation Young Investigator Award (T. P.); a US Northeast Biodefense Center ARRA award (U54-AI057158 to R. R.); the US National Institutes of Health (R01CA120196 and R01CA129382 to A. F.); the Rally across America Foundation (A. F); the Swim across America Foundation (A. F.); the Golfers against Cancer Foundation (A. F.); and a Leukemia and Lymphoma Society Scholar Award (A. F.). We thank the Pediatric Cardiosurgery Units from Centro Especial Ramon y Cajal and Ciudad Sanitaria La Paz (Madrid, Spain) for thymus samples. NR 28 TC 119 Z9 119 U1 3 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2010 VL 42 IS 4 BP 338 EP U95 DI 10.1038/ng.542 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 576NE UT WOS:000276150500014 PM 20228800 ER PT J AU He, HSHS Meyer, CA Shin, HJ Bailey, ST Wei, G Wang, QB Zhang, Y Xu, KX Ni, M Lupien, M Mieczkowski, P Lieb, JD Zhao, KJ Brown, M Liu, XS AF He, Housheng Hansen Meyer, Clifford A. Shin, Hyunjin Bailey, Shannon T. Wei, Gang Wang, Qianben Zhang, Yong Xu, Kexin Ni, Min Lupien, Mathieu Mieczkowski, Piotr Lieb, Jason D. Zhao, Keji Brown, Myles Liu, X. Shirley TI Nucleosome dynamics define transcriptional enhancers SO NATURE GENETICS LA English DT Article ID ANDROGEN RECEPTOR; PROSTATE-CANCER; HIGH-RESOLUTION; HUMAN GENOME; CHROMATIN-STRUCTURE; CHIP-SEQ; PROMOTERS; GENE; NKX3.1; MODEL AB Chromatin plays a central role in eukaryotic gene regulation. We performed genome-wide mapping of epigenetically marked nucleosomes to determine their position both near transcription start sites and at distal regulatory elements, including enhancers. In prostate cancer cells, where androgen receptor binds primarily to enhancers, we found that androgen treatment dismisses a central nucleosome present at androgen receptor binding sites that is flanked by a pair of marked nucleosomes. A new quantitative model built on the behavior of such nucleosome pairs correctly identified regions bound by the regulators of the immediate androgen response, including androgen receptor and FOXA1. More importantly, this model also correctly predicted previously unidentified binding sites for other transcription factors present after prolonged androgen stimulation, including OCT1 and NKX3-1. Therefore, quantitative modeling of enhancer structure provides a powerful predictive method to infer the identity of transcription factors involved in cellular responses to specific stimuli. C1 [He, Housheng Hansen; Meyer, Clifford A.; Shin, Hyunjin; Zhang, Yong; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [He, Housheng Hansen; Meyer, Clifford A.; Shin, Hyunjin; Zhang, Yong; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [He, Housheng Hansen; Bailey, Shannon T.; Wang, Qianben; Xu, Kexin; Ni, Min; Lupien, Mathieu; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [He, Housheng Hansen; Bailey, Shannon T.; Wang, Qianben; Xu, Kexin; Ni, Min; Lupien, Mathieu; Brown, Myles] Harvard Univ, Sch Med, Boston, MA USA. [Wei, Gang; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Mieczkowski, Piotr; Lieb, Jason D.] Univ N Carolina, Dept Biol, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Mieczkowski, Piotr; Lieb, Jason D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Liu, XS (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu; xsliu@jimmy.harvard.edu RI Wei, Gang/A-3291-2011; Zhang, Yong/B-4838-2011; He, Housheng/G-9614-2011; Wang, Qianben/E-4267-2011; Bailey, Shannon/B-8045-2014; OI Zhang, Yong/0000-0001-6316-2734; Brown, Myles/0000-0002-8213-1658 FU US National Institutes of Health [1R01 HG004069-02, 2P50 CA090381-06]; Department of Defense [W81XWH-07-1-0037]; Prostate Cancer Foundation FX This work was supported by grants from US National Institutes of Health (1R01 HG004069-02 to X. S. L., and 2P50 CA090381-06 to X. S. L. and M. B.), the Department of Defense (W81XWH-07-1-0037 to X. S. L.) and the Prostate Cancer Foundation (to M. B.). NR 32 TC 250 Z9 253 U1 6 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2010 VL 42 IS 4 BP 343 EP U101 DI 10.1038/ng.545 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 576NE UT WOS:000276150500015 PM 20208536 ER PT J AU Myers, MG Kahn, CR Accili, D AF Myers, Martin G., Jr. Kahn, C. Ronald Accili, Domenico TI Leptin therapy for type 1 diabetes gains traction SO NATURE MEDICINE LA English DT Editorial Material C1 [Myers, Martin G., Jr.] Univ Michigan Med Sch, Dept Med, Ann Arbor, MI USA. [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA USA. [Kahn, C. Ronald] Harvard Med Sch, Boston, MA USA. [Accili, Domenico] Columbia Univ, Dept Med, New York, NY USA. RP Myers, MG (reprint author), Univ Michigan Med Sch, Dept Med, Ann Arbor, MI USA. FU NIDDK NIH HHS [R01 DK082659] NR 1 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2010 VL 16 IS 4 BP 380 EP 380 DI 10.1038/nm0410-380 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 580KJ UT WOS:000276446800056 PM 20376045 ER PT J AU Winnay, JN Boucher, J Mori, MA Ueki, K Kahn, CR AF Winnay, Jonathon N. Boucher, Jeremie Mori, Marcelo A. Ueki, Kohjiro Kahn, C. Ronald TI A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response SO NATURE MEDICINE LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; INSULIN-RESISTANCE; PHOSPHATIDYLINOSITOL 3-KINASE; ER STRESS; SKELETAL-MUSCLE; MESSENGER-RNA; PURIFICATION METHOD; METABOLIC SYNDROME; P85-ALPHA SUBUNIT; ADIPOSE-TISSUE AB Class Ia phosphoinositide 3-kinase (PI3K), an essential mediator of the metabolic actions of insulin, is composed of a catalytic (p110 alpha or p110 beta) and regulatory (p85 alpha, p85 beta or p55 gamma) subunit. Here we show that p85 alpha interacts with X-box-binding protein-1 (XBP-1), a transcriptional mediator of the unfolded protein response (UPR), in an endoplasmic reticulum (ER) stress-dependent manner. Cell lines with knockout or knockdown of p85 alpha show marked alterations in the UPR, including reduced ER stress-dependent accumulation of nuclear XBP-1, decreased induction of UPR target genes and increased rates of apoptosis. This is associated with a decreased activation of inositol-requiring protein-1 alpha (IRE1 alpha) and activating transcription factor-6 alpha (ATF6 alpha). Mice with deletion of p85 alpha in liver (L-Pik3r1(-/-)) show a similar attenuated UPR after tunicamycin administration, leading to an increased inflammatory response. Thus, p85 alpha forms a previously unrecognized link between the PI3K pathway, which is central to insulin action, and the regulation of the cellular response to ER stress, a state that when unresolved leads to insulin resistance. C1 [Winnay, Jonathon N.; Boucher, Jeremie; Mori, Marcelo A.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. [Ueki, Kohjiro] Univ Tokyo, Dept Metab Dis, Grad Sch Med, Tokyo, Japan. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu FU US National Institutes of Health [DK55545, DK07260-30]; Joslin Diabetes and Endocrine Research Center [DK36836] FX We would like to thank D. Ron (New York University School of Medicine) for providing the Flag-XBP-1u and Flag-XBP-1s expression plasmids. This work was supported by US National Institutes of Health grant DK55545 and National Institutes of Health training grant DK07260-30, as well as Core laboratory support from the Joslin Diabetes and Endocrine Research Center grant DK36836. We would also like to thank U. Ozcan for useful advice and discussion and S. Green and S. Flaherty for assistance in preparation of this manuscript. NR 57 TC 91 Z9 97 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2010 VL 16 IS 4 BP 438 EP U120 DI 10.1038/nm.2121 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 580KJ UT WOS:000276446800048 PM 20348923 ER PT J AU McMillin, DW Delmore, J Weisberg, E Negri, JM Geer, DC Klippel, S Mitsiades, N Schlossman, RL Munshi, NC Kung, AL Griffin, JD Richardson, PG Anderson, KC Mitsiades, CS AF McMillin, Douglas W. Delmore, Jake Weisberg, Ellen Negri, Joseph M. Geer, D. Corey Klippel, Steffen Mitsiades, Nicholas Schlossman, Robert L. Munshi, Nikhil C. Kung, Andrew L. Griffin, James D. Richardson, Paul G. Anderson, Kenneth C. Mitsiades, Constantine S. TI Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity SO NATURE MEDICINE LA English DT Article ID MULTIPLE-MYELOMA CELLS; LENALIDOMIDE PLUS DEXAMETHASONE; HISTONE DEACETYLASE INHIBITION; BONE-MARROW STROMA; GENE-EXPRESSION; CLINICAL-IMPLICATIONS; MOLECULAR SEQUELAE; RESISTANCE; BORTEZOMIB; IDENTIFICATION AB Conventional anticancer drug screening is typically performed in the absence of accessory cells of the tumor microenvironment, which can profoundly alter antitumor drug activity. To address this limitation, we developed the tumor cell-specific in vitro bioluminescence imaging (CS-BLI) assay. Tumor cells (for example, myeloma, leukemia and solid tumors) stably expressing luciferase are cultured with nonmalignant accessory cells (for example, stromal cells) for selective quantification of tumor cell viability, in presence versus absence of stromal cells or drug treatment. CS-BLI is high-throughput scalable and identifies stroma-induced chemoresistance in diverse malignancies, including imatinib resistance in leukemic cells. A stroma-induced signature in tumor cells correlates with adverse clinical prognosis and includes signatures for activated Akt, Ras, NF-kappa B, HIF-1 alpha, myc, hTERT and IRF4; for biological aggressiveness; and for self-renewal. Unlike conventional screening, CS-BLI can also identify agents with increased activity against tumor cells interacting with stroma. One such compound, reversine, shows more potent activity in an orthotopic model of diffuse myeloma bone lesions than in conventional subcutaneous xenografts. Use of CS-BLI, therefore, enables refined screening of candidate anticancer agents to enrich preclinical pipelines with potential therapeutics that overcome stroma-mediated drug resistance and can act in a synthetic lethal manner in the context of tumor-stroma interactions. C1 [McMillin, Douglas W.; Delmore, Jake; Negri, Joseph M.; Geer, D. Corey; Klippel, Steffen; Mitsiades, Nicholas; Schlossman, Robert L.; Munshi, Nikhil C.; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [McMillin, Douglas W.; Delmore, Jake; Weisberg, Ellen; Negri, Joseph M.; Geer, D. Corey; Klippel, Steffen; Mitsiades, Nicholas; Schlossman, Robert L.; Munshi, Nikhil C.; Griffin, James D.; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA USA. [McMillin, Douglas W.; Delmore, Jake; Weisberg, Ellen; Negri, Joseph M.; Geer, D. Corey; Klippel, Steffen; Schlossman, Robert L.; Munshi, Nikhil C.; Griffin, James D.; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Munshi, Nikhil C.] Boston VA Healthcare Syst, Boston, MA USA. [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Mitsiades, CS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. EM constantine_mitsiades@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU Dunkin Donuts Rising Stars program at the Dana-Farber Cancer Institute; Chambers Medical Foundation; Steven Cobb Foundation; US National Institutes of Health [R01CA050947] FX Supported by the Dunkin Donuts Rising Stars program at the Dana-Farber Cancer Institute (C. S. M.), the Chambers Medical Foundation (C. S. M. and P. G. R.), the Steven Cobb Foundation (D. W. M., C. S. M.) and US National Institutes of Health grant R01CA050947 (C. S. M. and K. C. A.). We wish to thank T. Libermann and M. Joseph-Bruno (Harvard Institutes of Medicine Genomics Core) for generation of gene expression data and L. Buon for help with bioinformatic analyses. NR 38 TC 156 Z9 163 U1 3 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2010 VL 16 IS 4 BP 483 EP U171 DI 10.1038/nm.2112 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 580KJ UT WOS:000276446800055 PM 20228816 ER PT J AU Kim, P Chung, E Yamashita, H Hung, KE Mizoguchi, A Kucherlapati, R Fukumura, D Jain, RK Yun, SH AF Kim, Pilhan Chung, Euiheon Yamashita, Hiroshi Hung, Kenneth E. Mizoguchi, Atsushi Kucherlapati, Raju Fukumura, Dai Jain, Rakesh K. Yun, Seok H. TI In vivo wide-area cellular imaging by side-view endomicroscopy SO NATURE METHODS LA English DT Article ID MICROENDOSCOPY; COLONOSCOPY; DISEASE; MICE AB In vivo imaging of small animals offers several possibilities for studying normal and disease biology, but visualizing organs with single-cell resolution is challenging. We describe rotational side-view confocal endomicroscopy, which enables cellular imaging of gastrointestinal and respiratory tracts in mice and may be extensible to imaging organ parenchyma such as cerebral cortex. We monitored cell infiltration, vascular changes and tumor progression during inflammation and tumorigenesis in colon over several months. C1 [Kim, Pilhan; Yun, Seok H.] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02115 USA. [Chung, Euiheon; Yamashita, Hiroshi; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02115 USA. [Chung, Euiheon; Yamashita, Hiroshi; Mizoguchi, Atsushi; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hung, Kenneth E.] Tufts Med Ctr, Div Gastroenterol, Boston, MA USA. [Mizoguchi, Atsushi] Harvard Univ, Sch Med, Dept Pathol, Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA. [Kucherlapati, Raju] Brigham & Womens Hosp, Dept Genet, Boston, MA 02115 USA. [Yun, Seok H.] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Taejon 305701, South Korea. [Yun, Seok H.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02115 USA. EM syun@hms.harvard.edu RI Kim, Pilhan/C-1836-2011 OI Kim, Pilhan/0000-0001-8388-1840 FU Wellman Center for Photomedicine, Human Frontier Science Program; National Research Foundation of Korea [R31-2008-000-10071-0]; US National Institutes of Health [R21AI081010, RC1DK086242, RC2DK088661, U54CA143837, U01CA084301, R01CA85140, P01CA08124, R01CA96915, R01CA126642] FX This work was supported by the Wellman Center for Photomedicine, Human Frontier Science Program (cross-disciplinary fellowship 2006), Tosteson Fellowship, National Research Foundation of Korea (R31-2008-000-10071-0) and the US National Institutes of Health (R21AI081010, RC1DK086242, RC2DK088661, U54CA143837, U01CA084301, R01CA85140, P01CA08124, R01CA96915 and R01CA126642). NR 15 TC 76 Z9 76 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD APR PY 2010 VL 7 IS 4 BP 303 EP 305 DI 10.1038/NMETH.1440 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 576NF UT WOS:000276150600021 PM 20228814 ER PT J AU Sharma, SV Haber, DA Settleman, J AF Sharma, Sreenath V. Haber, Daniel A. Settleman, Jeff TI Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents SO NATURE REVIEWS CANCER LA English DT Review ID GROWTH-FACTOR RECEPTOR; NATIONAL-CANCER-INSTITUTE; METASTATIC BREAST-CANCER; HUMAN-TUMOR XENOGRAFTS; GASTROINTESTINAL STROMAL TUMORS; GENOTYPE-CORRELATED SENSITIVITY; 3-DIMENSIONAL CULTURE MODELS; PREVIOUSLY TREATED PATIENTS; TYROSINE KINASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA AB Efforts to discover new cancer drugs and predict their clinical activity are limited by the fact that laboratory models to test drug efficacy do not faithfully recapitulate this complex disease. One important model system for evaluating candidate anticancer agents is human tumour-derived cell lines. Although cultured cancer cells can exhibit distinct properties compared with their naturally growing counterparts, recent technologies that facilitate the parallel analysis of large panels of such lines, together with genomic technologies that define their genetic constitution, have revitalized efforts to use cancer cell lines to assess the clinical utility of new investigational cancer drugs and to discover predictive biomarkers. C1 [Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu RI Bell, Tiffany/F-4403-2010 NR 158 TC 206 Z9 214 U1 7 U2 60 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 APR PY 2010 VL 10 IS 4 BP 241 EP 253 DI 10.1038/nrc2820 PG 13 WC Oncology SC Oncology GA 573RQ UT WOS:000275932700008 PM 20300105 ER PT J AU Rades, D Schild, SE Abrahm, JL AF Rades, Dirk Schild, Steven E. Abrahm, Janet L. TI Treatment of painful bone metastases SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID SPINAL-CORD COMPRESSION; OSTEOPOROTIC VERTEBRAL FRACTURES; SINGLE FRACTION RADIOTHERAPY; LONG-COURSE RADIOTHERAPY; BREAST-CANCER PATIENTS; RANDOMIZED-TRIAL; PALLIATIVE RADIOTHERAPY; ZOLEDRONIC ACID; 8 GY; PROGNOSTIC-FACTORS AB Bone metastases are the most common cause of cancer-related pain. Radiotherapy is a safe and effective therapy and is well established for such a situation. A fractionation regimen with a short overall treatment time (<= 1 week) would be preferred if it was as effective as longer courses (2-4 weeks). Randomized clinical trials and meta-analyses have demonstrated that single-fraction radiotherapy with 1 x 8 Gy is as effective for pain relief as multi-fraction regimens such as 5 x 4 Gy in 1 week or 10 x 3 Gy in 2 weeks. Re-irradiation for recurrent pain in the irradiated region is required more often after single-fraction radiotherapy than multi-fraction radiotherapy; however, re-irradiation following single-fraction radiotherapy is safe and effective. Thus, 1 x 8 Gy is considered the standard regimen for uncomplicated painful bone metastases without pathological fractures or spinal cord compression. Multi-fraction radiotherapy results in significantly better remineralization of the osteolytic bone than single-fraction radiotherapy. Remineralization is important for preventing or treating pathological fractures. Multi-fraction long-course radiotherapy results in fewer recurrences of spinal-cord compression within the irradiated spinal region. Thus, long-course multi-fraction radiotherapy should be reserved for patients with a relatively favorable survival prognosis. C1 [Rades, Dirk] Univ Lubeck, Dept Radiat Oncol, D-23538 Lubeck, Germany. [Schild, Steven E.] Mayo Clin, Dept Radiat Oncol, Scottsdale, AZ 85259 USA. [Abrahm, Janet L.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Rades, D (reprint author), Univ Lubeck, Dept Radiat Oncol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM rades.dirk@gmx.net OI schild, steven/0000-0002-2850-4126 NR 82 TC 25 Z9 26 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD APR PY 2010 VL 7 IS 4 BP 220 EP 229 DI 10.1038/nrclinonc.2010.17 PG 10 WC Oncology SC Oncology GA 576NT UT WOS:000276152300013 PM 20234353 ER PT J AU Astronomo, RD Burton, DR AF Astronomo, Rena D. Burton, Dennis R. TI Carbohydrate vaccines: developing sweet solutions to sticky situations? SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID INFLUENZAE TYPE-B; KEYHOLE LIMPET HEMOCYANIN; CRYPTOCOCCUS-NEOFORMANS INFECTION; POLYSACCHARIDE CONJUGATE VACCINE; IMMUNOLOGICAL ADJUVANT QS-21; NEUTRALIZING ANTIBODY 2G12; RELAPSED PROSTATE-CANCER; GLYCAN-BINDING-PROTEINS; MONOCLONAL-ANTIBODIES; TRICHINELLA-SPIRALIS AB Recent technological advances in glycobiology and glycochemistry are paving the way for a new era in carbohydrate vaccine design. This is enabling greater efficiency in the identification, synthesis and evaluation of unique glycan epitopes found on a plethora of pathogens and malignant cells. Here, we review the progress being made in addressing challenges posed by targeting the surface carbohydrates of bacteria, protozoa, helminths, viruses, fungi and cancer cells for vaccine purposes. C1 [Astronomo, Rena D.] Scripps Res Inst, Neutralizing Antibody Ctr, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Neutralizing Antibody Ctr, Int AIDS Vaccine Initiat, La Jolla, CA 92037 USA. [Burton, Dennis R.] Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA. RP Astronomo, RD (reprint author), Scripps Res Inst, Neutralizing Antibody Ctr, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd,IMM 2, La Jolla, CA 92037 USA. EM rastrono@fhcrc.org; burton@scripps.edu FU Natural Sciences and Engineering Research Council of Canada; Neutralizing Antibody Consortium of the International AIDS Vaccine Initiative; National Institute of Allergy and Infectious Diseases FX We are grateful to R. Woods, J. Paulson, I. Wilson and M. Manchester for critical reading of the manuscript. We also appreciate the feedback and suggestions from K. Doores and M. Huber during the writing process. We thank C. Corbacci for the considerable time, effort and creativity she devoted to figure design for this Review. The authors' work is supported by the Natural Sciences and Engineering Research Council of Canada ( to R. D. A.), the Neutralizing Antibody Consortium of the International AIDS Vaccine Initiative ( to D. R. B.) and the National Institute of Allergy and Infectious Diseases. NR 193 TC 232 Z9 238 U1 14 U2 112 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 EI 1474-1784 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD APR PY 2010 VL 9 IS 4 BP 308 EP 324 DI 10.1038/nrd3012 PG 17 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 577VD UT WOS:000276251200024 PM 20357803 ER PT J AU Tran, TT Kahn, CR AF Tran, Thien T. Kahn, C. Ronald TI Transplantation of adipose tissue and stem cells: role in metabolism and disease SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Review ID BODY-FAT DISTRIBUTION; MOLECULAR-WEIGHT ADIPONECTIN; SUBCUTANEOUS ABDOMINAL FAT; DIET-INDUCED THERMOGENESIS; UNCOUPLING PROTEIN GENE; MOUSE OB-OB; IN-VIVO; INSULIN SENSITIVITY; STROMAL CELLS; BROWN FAT AB Humans and other mammals have three main adipose tissue depots: visceral white adipose tissue, subcutaneous white adipose tissue and brown adipose tissue, each of which possesses unique cell-autonomous properties. In contrast to visceral adipose tissue, which can induce detrimental metabolic effects, subcutaneous white adipose tissue and brown adipose tissue have the potential to benefit metabolism by improving glucose homeostasis and increasing energy consumption. In addition, adipose tissue contains adipose-derived stem cells, which possess the ability to differentiate into multiple lineages, a property that might be of value for the repair or replacement of various damaged cell types. Adipose tissue transplantation has primarily been used as a tool to study physiology and for human reconstructive surgery. Transplantation of adipose tissue is, however, now being explored as a possible tool to promote the beneficial metabolic effects of subcutaneous white adipose tissue and brown adipose tissue, as well as adipose-derived stem cells. Ultimately, the clinical applicability of adipose tissue transplantation for the treatment of obesity and metabolic disorders will reside in the achievable level of safety, reliability and efficacy compared with other treatments. C1 [Tran, Thien T.; Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. [Tran, Thien T.; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIH [2 P30 DK46200-16, 1 R01 DK082659]; Mary K. Iacocca Professorship FX T. T. Tran is supported by NIH research grant 2 P30 DK46200-16. C. R. Kahn is supported by NIH research grant 1 R01 DK082659 and the Mary K. Iacocca Professorship. NR 197 TC 105 Z9 114 U1 3 U2 40 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD APR PY 2010 VL 6 IS 4 BP 195 EP 213 DI 10.1038/nrendo.2010.20 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 573ZX UT WOS:000275959300007 PM 20195269 ER PT J AU Fehon, RG McClatchey, AI Bretscher, A AF Fehon, Richard G. McClatchey, Andrea I. Bretscher, Anthony TI Organizing the cell cortex: the role of ERM proteins SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID EPITHELIAL-MESENCHYMAL TRANSITION; CORTICAL ACTIN ORGANIZATION; MESSENGER-RNA LOCALIZATION; MOESIN-DEFICIENT MICE; RADIXIN FERM DOMAIN; N-TERMINAL DOMAIN; STRUCTURAL BASIS; EZRIN/RADIXIN/MOESIN PROTEINS; TUMOR-SUPPRESSOR; BINDING-SITE AB Specialized membrane domains are an important feature of almost all cells. In particular, they are essential to tissues that have a highly organized cell cortex, such as the intestinal brush border epithelium. The ERM proteins (ezrin, radixin and moesin) have a crucial role in organizing membrane domains through their ability to interact with transmembrane proteins and the cytoskeleton. In doing so, they can provide structural links to strengthen the cell cortex and regulate the activities of signal transduction pathways. Recent studies examining the structure and in vivo functions of ERMs have greatly advanced our understanding of the importance of membrane-cytoskeleton interactions. C1 [Fehon, Richard G.] Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. [McClatchey, Andrea I.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [McClatchey, Andrea I.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. [Bretscher, Anthony] Cornell Univ, Weill Inst Cell & Mol Biol, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. RP Fehon, RG (reprint author), Univ Chicago, Dept Mol Genet & Cell Biol, 920 E 58Th St, Chicago, IL 60637 USA. EM rfehon@uchicago.edu; mcclatch@helix.mgh.harvard.edu; apb5@cornell.edu FU National Institutes of Health; US Army Neurofibromatosis Research Program FX We thank the members of our laboratories for their contributions and helpful discussions. We apologize for work that was omitted owing to space limitations. Work in our laboratories was supported by grants from the National Institutes of Health (A.B., R. G.F. and A.I.M.) and the US Army Neurofibromatosis Research Program (A.B. and A.I.M.). NR 113 TC 405 Z9 414 U1 5 U2 48 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD APR PY 2010 VL 11 IS 4 BP 276 EP 287 DI 10.1038/nrm2866 PG 12 WC Cell Biology SC Cell Biology GA 572RL UT WOS:000275850400012 PM 20308985 ER PT J AU Velez, JCQ Janech, MG AF Velez, Juan Carlos Q. Janech, Michael G. TI A case of lactic acidosis induced by linezolid SO NATURE REVIEWS NEPHROLOGY LA English DT Article ID MITOCHONDRIAL PROTEIN-SYNTHESIS; OXAZOLIDINONE ANTIBIOTICS; SEROTONIN SYNDROME; INHIBITION; INFECTIONS; PHARMACOKINETICS; HEMODIALYSIS; RECIPIENT; TOXICITY; RIBOSOME AB Background. A 36-year-old African American man with end-stage renal disease on chronic maintenance hemodialysis was transferred first from a hospital to a long-term acute care facility for advanced care then to the intensive care unit of our university hospital with unexplained abdominal pain, nausea, hypotension, altered mental status and anion gap metabolic acidosis. Subsequent review of the patient's medication list revealed that the he had been on linezolid for 6 weeks for the treatment of vancomycin-resistant Enterococcus fecalis bacteremia. Investigations. Medical history, physical examination, laboratory tests, CT imaging of the thorax, abdomen and pelvis and PCR-based tests to determine the presence of polymorphisms in the 16S ribosomal RNA gene. Diagnosis. Lactic acidosis associated with prolonged exposure to linezolid. Management. Discontinuation of linezolid. C1 [Velez, Juan Carlos Q.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Janech, Michael G.] Ralph H Johnson VA Med Ctr, Med & Res Serv, Charleston, SC 29403 USA. RP Velez, JCQ (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,Clin Sci Bldg,Room 829, Charleston, SC 29425 USA. EM velezj@musc.edu RI Velez, Juan Carlos/N-3782-2016; OI Janech, Michael/0000-0002-3202-4811 FU NIH NIDDK; Veterans Affairs CDA-2 Career Development Award; Nephcure Foundation FX The research work of Dr J. C. Q. Velez is supported by a NIH NIDDK K08 Career Development Award. The research work of Dr M. G. Janech is supported by a Veterans Affairs CDA-2 Career Development Award and the Nephcure Foundation. NR 36 TC 11 Z9 13 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD APR PY 2010 VL 6 IS 4 BP 236 EP 242 DI 10.1038/nrneph.2010.20 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 575EF UT WOS:000276048800009 PM 20348931 ER PT J AU Canalejo, A Canalejo, R Rodriguez, ME Martinez-Moreno, JM Felsenfeld, AJ Rodriguez, M Almaden, Y AF Canalejo, Antonio Canalejo, Rocio Encarnacion Rodriguez, M. Martinez-Moreno, Julio M. Felsenfeld, Arnold J. Rodriguez, Mariano Almaden, Yolanda TI Development of parathyroid gland hyperplasia without uremia: role of dietary calcium and phosphate SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE calcium-sensing receptor; dietary calcium; dietary phosphate; parathyroid cell proliferation; vitamin D receptor ID SENSING RECEPTOR EXPRESSION; CHRONIC-RENAL-FAILURE; VITAMIN-D-RECEPTOR; SECONDARY HYPERPARATHYROIDISM; CELL-PROLIFERATION; TGF-ALPHA; PHOSPHORUS RESTRICTION; GENE-EXPRESSION; DOWN-REGULATION; RATS AB Background. Many experimental studies have demonstrated that parathyroid cell proliferation is induced by uremia and further aggravated by hypocalcemia, phosphorus retention and vitamin D deficiency. However, these factors may also promote parathyroid growth without uremia. In the present study, we examined the onset and progression of parathyroid hyperplasia regardless of the uremic setting, a situation that might occur soon during the early renal disease. Thus, the novelty of this work resides in the close examination of the time course for the expected changes in proliferation rates and their association with parathyroid hormone (PTH) release in normal rats under the physiological demands of a high-phosphate diet (HPD) or a low-calcium diet (LCD). Methods. We evaluated the functional response of the parathyroid glands in normal rats to different physiological demands an HPD 0.6% Ca, 1.2% P) and LCD 0.2% Ca, 0.6% P) and compared it with that of uremic rats. Furthermore, we also evaluated the time course for the reversal of high-P and low-Ca-induced parathyroid cell growth and PTH upon normalization of dietary Ca and P intake (0.6% Ca, 0.6% P). Proliferation was Measured by flow cytometry and calcium receptor (CaR) and vitamin D receptor (VDR) expression were assessed by qRT-PCR. Results. The pattern in the development of parathyroid hyperplasia by the two dietary models was different. The HPD produced a stronger stimulus than the number of proliferating cells doubled after only 1 day, while the LCD required 5 days to induce an increase; the elevated calcitriol might be a mitigating factor. The increase in cell proliferation was accompanied by a transient down-regulation of VDR expression (higher in the HPD); the expression of CaR was not affected by either diet. Cell proliferation and VDR mRNA levels were restored to control values by Day 15; it is as though the gland had attained a sufficient level of hyperplasia to respond to the PTH challenge. Compared to normal rats, the response of uremic rats to the HPD showed sustained and much higher rates of PTH secretion and cell proliferation and sustained down-regulation of both VDR mRNA and CaR mRNA. Finally, the recovery from the HPD or LCD to a control diet resulted in a rapid restoration of PTH values (1 to 2 days), but the reduction in cell proliferation was delayed (3 to 5 days). Conclusions. Regardless of uremia, a physiological demand to increase the PTH secretion driven either by a high P or a low Ca intake is able to induce a different pattern of parathyroid hyperplasia, which might be aggravated by the down-regulation of VDR expression. The recovery from the HPD or LCD to a control diet results in a more rapid reduction in PTH than in cell proliferation. C1 [Canalejo, Antonio] Univ Huelva, Dept Environm Biol & Publ Hlth, Huelva, Spain. [Canalejo, Rocio; Encarnacion Rodriguez, M.; Martinez-Moreno, Julio M.; Rodriguez, Mariano; Almaden, Yolanda] Hosp Univ Reina Sofia, Serv Nephrol, Unit Invest, Cordoba, Spain. [Felsenfeld, Arnold J.] W Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. [Felsenfeld, Arnold J.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Canalejo, A (reprint author), Univ Huelva, Dept Environm Biol & Publ Hlth, Huelva, Spain. EM antonio.canalejo@dbasp.uhu.es RI Rodriguez, teresa/H-5452-2011; Canalejo, Antonio/L-8407-2014; OI Canalejo, Antonio/0000-0003-2098-8960; Rodriguez, Mariano/0000-0002-9380-6614 FU Group CTS-179; Fundacion Nefrologica; Consejeria de Salud de Is Junta de Andalucia [PI0025/2007]; Fundacion Progreso y Salud; Consejeria de Salud; Junta de Andalucia; FIS; Ministerio de Sanidad de Espana; [PI07-0287]; [PI07-0315] FX The work reported here was supported by Government Grants PI07-0287 and PI07-0315, Group CTS-179, Fundacion Nefrologica, Fundacion Hospital Reina Sofia-CajaSur and research grant PI0025/2007 from Consejeria de Salud de Is Junta de Andalucia. Y.A. is a senior researcher supported by the Fundacion Progreso y Salud, Consejeria de Salud, Junta de Andalucia. R.C. and M.E.R. are pre-doctoral fellows supported by Junta de Andalucia and FIS, Ministerio de Sanidad de Espana, respectively. NR 40 TC 4 Z9 4 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD APR PY 2010 VL 25 IS 4 BP 1087 EP 1097 DI 10.1093/ndt/gfp616 PG 11 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 591DO UT WOS:000277279400014 PM 19934096 ER PT J AU Farrar, CT Kamoun, WS Ley, CD Kim, YR Kwon, SJ Dai, GP Rosen, BR di Tomaso, E Jain, RK Sorensen, AG AF Farrar, Christian T. Kamoun, Walid S. Ley, Carsten D. Kim, Young R. Kwon, Seon J. Dai, Guangping Rosen, Bruce R. di Tomaso, Emmanuelle Jain, Rakesh K. Sorensen, A. Gregory TI In vivo validation of MRI vessel caliber index measurement methods with intravital optical microscopy in a U87 mouse brain tumor model SO NEURO-ONCOLOGY LA English DT Article DE brain tumor; intravital microscopy; mouse; MRI; tumor angiogenesis; vessel caliber index ID CEREBRAL BLOOD-VOLUME; CONTRAST AGENT EXTRAVASATION; GRADIENT-ECHO; KINASE INHIBITOR; ANGIOGENESIS; MAPS; VASCULATURE; VASCULARITY; GRADE; SIZE AB The vessel caliber index (VCI), a magnetic resonance imaging biomarker of the average blood vessel diameter, is increasingly being used as a tool for assessing tumor angiogenesis and response to antiangiogenic therapy. However, although the VCI has been correlated with histological vessel diameters, good quantitative agreement with histology has been lacking. In addition, no VCI validation studies have been performed in vivo where the structural deformations frequently associated with histological tissue preparation are not present. This study employs intravital optical microscopy (IVM) measurements of cerebral blood vessel diameters in a mouse orthotopic glioma model to provide the first such in vivo validation. Two VCI correlation models, both a linear and a 3/2-power dependence on the Delta R2*/Delta R2 ratio, were compared with the IVM data. The linear VCI model, determined from steady-state susceptibility contrast (SSC) images, was found to be in excellent quantitative agreement with the intravitally determined VCI for separate tumor size matched groups of mice. In addition, preliminary data indicate that the VCI is independent of whether a dynamic susceptibility contrast or SSC measurement method is used. C1 [Farrar, Christian T.; Kim, Young R.; Kwon, Seon J.; Dai, Guangping; Rosen, Bruce R.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kamoun, Walid S.; Ley, Carsten D.; di Tomaso, Emmanuelle; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Farrar, CT (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM cfarrar@nmr.mgh.harvard.edu FU National Institutes of Health [P41-RR14075, P01-CA80124, R01-CA115767]; National Cancer Institute [T32-CA009502-19]; National Institute on Aging [K25-AG029415]; Susan G. Komen foundation; Harboe Foundation; A.P. Moller Foundation; Dagmar-Marshall Foundation FX This research was supported by the National Institutes of Health (P41-RR14075, P01-CA80124, R01-CA115767) and by gifts from AstraZeneca Pharmaceuticals. CTF gratefully acknowledges support from the National Cancer Institute (T32-CA009502-19) and the National Institute on Aging (K25-AG029415). WSK gratefully acknowledges support from the Susan G. Komen foundation. CDL gratefully acknowledges support from the Harboe Foundation, the A.P. Moller Foundation, and the Dagmar-Marshall Foundation. NR 36 TC 18 Z9 19 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2010 VL 12 IS 4 BP 341 EP 350 DI 10.1093/neuonc/nop032 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 580PY UT WOS:000276462600004 PM 20308312 ER PT J AU Borsook, D Sava, S Becerra, L AF Borsook, David Sava, Simona Becerra, Lino TI The Pain Imaging Revolution: Advancing Pain Into the 21st Century SO NEUROSCIENTIST LA English DT Review DE pain; neuroimaging; emotion; cognition; sensory ID MAGNETIC-RESONANCE-SPECTROSCOPY; CHRONIC BACK-PAIN; TRIGEMINAL NEUROPATHIC PAIN; MEDIAL PREFRONTAL CORTEX; NOXIOUS THERMAL STIMULI; CENTRAL-NERVOUS-SYSTEM; HUMAN CEREBRAL-CORTEX; DIFFUSION-TENSOR; MENSTRUAL-CYCLE; NEUROBIOLOGICAL MECHANISMS AB The great advances in brain imaging techniques over the last few decades have determined a shift in our understanding of chronic pain conditions and opened the door for new opportunities to develop better diagnoses and perhaps better drug treatments. Neuroimaging has helped shape the concept of chronic pain from a disease affecting mainly the somatosensory system, to a condition in which emotional, cognitive, and modulatory areas of the brain are affected, in addition to degenerative processes. All these contribute to the development and maintenance of pain symptoms and comorbid features, including alterations in anxiety, depression, and cognitive processes. In this article the authors review the current understanding of the brain changes in chronic pain and the developments made possible by the use of various brain imaging techniques. They also discuss the possible applications of brain imaging to developing a "pain phenotype" that could aid in diagnostic and treatment choices of chronic pain conditions. C1 [Sava, Simona] Childrens Hosp Boston, Dept Radiol, PAIN Grp, Waltham, MA 02453 USA. [Borsook, David; Becerra, Lino] McLean Hosp, Dept Psychiat, PAIN Grp, Belmont, MA 02178 USA. [Borsook, David; Becerra, Lino] Massachusetts Gen Hosp, Dept Radiol, Belmont, MA USA. [Borsook, David; Becerra, Lino] Massachusetts Gen Hosp, Dept Psychiat, Belmont, MA USA. RP Sava, S (reprint author), Childrens Hosp Boston, Dept Radiol, PAIN Grp, 9 Hope Ave, Waltham, MA 02453 USA. EM Simona.Sava@childrens.harvard.edu FU NINDS [K24 064050] FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: This work was supported by NINDS grant K24 064050 (DB). NR 120 TC 29 Z9 30 U1 1 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD APR PY 2010 VL 16 IS 2 BP 171 EP 185 DI 10.1177/1073858409349902 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 575QG UT WOS:000276081800012 PM 20400714 ER PT J AU Chernew, ME Baicker, K Hsu, J AF Chernew, Michael E. Baicker, Katherine Hsu, John TI The Specter of Financial Armageddon -- Health Care and Federal Debt in the United States. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Chernew, Michael E.; Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Baicker, Katherine] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Chernew, ME (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. NR 5 TC 37 Z9 37 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 1 PY 2010 VL 362 IS 13 BP 1166 EP 1168 DI 10.1056/NEJMp1002873 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 577QQ UT WOS:000276239500003 PM 20237338 ER PT J AU Klibanski, A AF Klibanski, Anne TI Prolactinomas SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TERM-FOLLOW-UP; VALVULAR HEART-DISEASE; SECRETING PITUITARY-ADENOMAS; CARDIAC-VALVE REGURGITATION; DOPAMINE AGONISTS; CABERGOLINE THERAPY; HYPERPROLACTINEMIC AMENORRHEA; TRANSSPHENOIDAL SURGERY; BROMOCRIPTINE; WITHDRAWAL AB A 42-year-old man presents with decreased libido, erectile dysfunction, and headaches. He reports no weight change, gynecomastia, fatigue, or other symptoms. He takes no medications. Testicular size is decreased on examination. His prolactin level is 648 mu g per liter (normal value, <15). Magnetic resonance imaging (MRI) reveals a sellar mass (2.5 by 1.5 by 2.0 cm) that is 5 mm below the optic chiasm and that extends bilaterally into the cavernous sinuses. What are the diagnostic and therapeutic considerations? C1 [Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,BUL457B, Boston, MA 02114 USA. EM aklibanski@partners.org FU Novartis; Pfizer FX Dr. Klibanski reports receiving grant support from Novartis and Pfizer. No other potential conflict of interest relevant to this article was reported. NR 50 TC 83 Z9 91 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 1 PY 2010 VL 362 IS 13 BP 1219 EP 1226 DI 10.1056/NEJMcp0912025 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 577QQ UT WOS:000276239500012 PM 20357284 ER PT J AU Whelan, P AF Whelan, Patrick TI Abortion Rates and Universal Health Care. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Whelan, Patrick] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Whelan, Patrick] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Whelan, Patrick] Harvard Univ, Sch Med, Boston, MA USA. RP Whelan, P (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 6 TC 2 Z9 2 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 1 PY 2010 VL 362 IS 13 DI 10.1056/NEJMp1002985 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 577QQ UT WOS:000276239500006 PM 20237339 ER PT J AU Forester, BP Berlow, YA Harper, DG Jensen, JE Lange, N Froimowitz, MP Ravichandran, C Iosifescu, DV Lukas, SE Renshaw, PF Cohen, BM AF Forester, Brent P. Berlow, Yosef A. Harper, David G. Jensen, J. Eric Lange, Nicholas Froimowitz, Michael P. Ravichandran, Caitlin Iosifescu, Dan V. Lukas, Scott E. Renshaw, Perry F. Cohen, Bruce M. TI Age-related changes in brain energetics and phospholipid metabolism SO NMR IN BIOMEDICINE LA English DT Article DE magnetic resonance spectroscopy, aging; mitochondria, ATP utilization ID MAGNETIC-RESONANCE-SPECTROSCOPY; MR-SPECTROSCOPY; WHITE-MATTER; ALZHEIMERS-DISEASE; P-31 MRS; 4 TESLA; PARTIAL SATURATION; GRAY; BIOENERGETICS; DEPRESSION AB Evidence suggests that mitochondria undergo functional and morphological changes with age. This study aimed to investigate the relationship of brain energy metabolism to healthy aging by assessing tissue specific differences in metabolites observable by phosphorus ((31)P) MRS. (31)P MRSI at 4 Tesla (T) was performed on 34 volunteers, aged 21-84, screened to exclude serious medical and psychiatric diagnoses. Linear mixed effects models were used to analyze the effects of age on phosphorus metabolite concentrations, intracellular magnesium and pH estimates in brain tissue. A significant age associated decrease in brain pH (-0.53% per decade), increase in PCr (1.1% per decade) and decrease in PME (1.7% per decade) were found in total tissue, with PCr effects localized to the gray matter. An increase in beta NTP as a function of age (1% per decade) approached significance (p=0.052). There were no effects demonstrated with increasing age for intracellular magnesium, PDE or inorganic phosphate. This study reports the effects of healthy aging on brain chemistry in the gray matter versus white matter using (31)P MRS measures of high energy phosphates, pH and membrane metabolism. Increased PCr, increased beta NTP (reflecting ATP) and reduced pH may reflect altered energy production with healthy aging. Unlike some previous studies of aging and brain chemistry, this study examined healthy, non-demented and psychiatrically stable older adults and specifically analyzed gray-white matter differences in brain metabolism. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Forester, Brent P.; Berlow, Yosef A.; Harper, David G.] McLean Hosp, Geriatr Psychiat Res Program, Belmont, MA 02178 USA. [Forester, Brent P.; Jensen, J. Eric; Lukas, Scott E.; Renshaw, Perry F.] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. [Forester, Brent P.; Berlow, Yosef A.; Harper, David G.; Jensen, J. Eric; Lange, Nicholas; Froimowitz, Michael P.; Ravichandran, Caitlin; Iosifescu, Dan V.; Lukas, Scott E.; Renshaw, Perry F.; Cohen, Bruce M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Lange, Nicholas; Froimowitz, Michael P.] McLean Hosp, Neurostat Lab, Belmont, MA 02178 USA. [Lange, Nicholas] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ravichandran, Caitlin] McLean Hosp, Lab Psychiat Biostat, Belmont, MA 02178 USA. [Iosifescu, Dan V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Renshaw, Perry F.] Univ Utah, Salt Lake City, UT USA. [Cohen, Bruce M.] McLean Hosp, Shervert H Frazier Res Inst, Belmont, MA 02178 USA. RP Forester, BP (reprint author), 115 Mill St, Belmont, MA 02478 USA. FU NARSAD (National Alliance for Research in Schizophrenia and Affective Disorders) [DA015116, MH058681]; NIMH [K23 MH067111, 1 MH K23 077287-01A2]; NINDS [NS37483]; Rogers Family Foundation FX This study was supported by the following funding sources NARSAD (National Alliance for Research in Schizophrenia and Affective Disorders) (Brent P. Forester), DA015116, MH058681 (Perry F. Renshaw), NIMH grant K23 MH067111 (Dan V. Iosifescu) and Shervert H Frazier Research Institute (Bruce M Cohen) NINDS grant NS37483 (Nicholas Lange), Rogers Family Foundation (Brent P Forester and Caitlin Ravichandran), NIMH 1 MH K23 077287-01A2 (Brent P Forester) The authors would also like to thank Brittany Jordan BA, Susan Kim BA and Matthew Woodward BA for their help in preparation of this manuscript NR 45 TC 22 Z9 23 U1 0 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD APR PY 2010 VL 23 IS 3 BP 242 EP 250 DI 10.1002/nbm.1444 PG 9 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 580JB UT WOS:000276443200003 PM 19908224 ER PT J AU Gazdzinski, S Millin, R Kaiser, LG Durazzo, TC Mueller, SG Weiner, MW Meyerhoff, DJ AF Gazdzinski, Stefan Millin, Rachel Kaiser, Lana G. Durazzo, Timothy C. Mueller, Susanne G. Weiner, Michael W. Meyerhoff, Dieter J. TI BMI and Neuronal Integrity in Healthy, Cognitively Normal Elderly: A Proton Magnetic Resonance Spectroscopy Study SO OBESITY LA English DT Article ID BODY-MASS INDEX; NORMAL HUMAN BRAIN; IN-VIVO; CENTRAL OBESITY; ALZHEIMERS-DISEASE; N-ACETYLASPARTATE; INCIDENT DEMENTIA; ADULTS; RISK; METABOLISM AB Recent studies associated excess body weight with brain structural alterations, poorer cognitive function, and lower prefrontal glucose metabolism. We found that higher BMI was related to lower concentrations of N-acetyl-aspartate (NAA, a marker of neuronal integrity) in a healthy middle-aged cohort, especially in frontal lobe. Here, we evaluated whether NAA was also associated with BMI in a healthy elderly cohort. We used 4 Tesla proton magnetic resonance spectroscopy ((1)H MRS) data from 23 healthy, cognitively normal elderly participants (69.4 +/- 6.9 years; 12 females) and measured concentrations of NAA, glutamate (Glu, involved in cellular metabolism), choline-containing compounds (Cho, involved in membrane metabolism), and creatine (Cr, involved in high-energy metabolism) in anterior (ACC) and posterior cingulate cortices (PCC). After adjustment for age, greater BMI was related to lower NAA/Cr and NAA/Cho ratios (beta < -0.56, P < 0.008) and lower Glu/Cr and Glu/Cho ratios (beta < -0.46, P < 0.02) in ACC. These associations were not significant in PCC (beta > -0.36, P > 0.09). The existence of an association between NAA and BMI in ACC but not in PCC is consistent with our previous study in healthy middle-aged individuals and with reports of lower frontal glucose metabolism in young healthy individuals with elevated BMI. Taken together, these results provide evidence that elevated BMI is associated with neuronal abnormalities mostly in frontal brain regions that subserve higher cognitive functions and impulse control. Future studies need to evaluate whether these metabolite abnormalities are involved in the development and maintenance of weight problems. C1 [Gazdzinski, Stefan; Millin, Rachel; Kaiser, Lana G.; Durazzo, Timothy C.; Mueller, Susanne G.; Weiner, Michael W.; Meyerhoff, Dieter J.] San Francisco Vet Adm Med Ctr, CIND, San Francisco, CA USA. [Kaiser, Lana G.; Durazzo, Timothy C.; Mueller, Susanne G.; Weiner, Michael W.; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Gazdzinski, S (reprint author), San Francisco Vet Adm Med Ctr, CIND, San Francisco, CA USA. EM Stefan.Gazdzinski@yahoo.com FU [AA10788]; [AG010897]; [AG12435] FX The study was supported by AA10788 (D.J.M.), AG010897 (M. W. W.), and AG12435 (M. W. W.). This material is the result of work supported with resources and the use of facilities at the Radiology Research Service of the Veterans Administration Medical Center in San Francisco. We thank Jeffrey Kasten, Kristen Peek, and Sky Raptentsetsang of the Center for Imaging of Neurodegenerative Diseases for data acquisition and processing. We extend our gratitude to Dr Lustig of the University of California San Francisco for critical review of this manuscript. NR 39 TC 32 Z9 32 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD APR PY 2010 VL 18 IS 4 BP 743 EP 748 DI 10.1038/oby.2009.325 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 583HR UT WOS:000276665200016 PM 19816410 ER PT J AU Shifren, JL Schiff, I AF Shifren, Jan L. Schiff, Isaac TI Role of Hormone Therapy in the Management of Menopause SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; CONJUGATED EQUINE ESTROGENS; CORONARY-HEART-DISEASE; BONE-MINERAL DENSITY; HEALTH INITIATIVE MEMORY; PLACEBO-CONTROLLED TRIAL; INVASIVE BREAST-CANCER; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY AB There are many options available to address the quality of life and health concerns of menopausal women. The principal indication for hormone therapy (HT) is the treatment of vasomotor symptoms, and benefits generally outweigh risks for healthy women with bothersome symptoms who elect HT at the time of menopause. Although HT increases the risk of coronary heart disease, recent analyses confirm that this increased risk occurs principally in older women and those a number of years beyond menopause. These findings do not support a role for HT in the prevention of heart disease but provide reassurance regarding the safety of use for hot flushes and night sweats in otherwise healthy women at the menopausal transition. An increased risk of breast cancer with extended use is another reason short-term treatment is advised. Hormone therapy prevents and treats osteoporosis but is rarely used solely for this indication. If only vaginal symptoms are present, low-dose local estrogen therapy is preferred. Contraindications to HT use include breast or endometrial cancer, cardiovascular disease, thromboembolic disorders, and active liver disease. Alternatives to HT should be advised for women with or at increased risk for these disorders. The lowest effective estrogen dose should be provided for the shortest duration necessary because risks increase with increasing age, time since menopause, and duration of use. Women must be informed of the potential benefits and risks of all therapeutic options, and care should be individualized, based on a woman's medical history, needs, and preferences. (Obstet Gynecol 2010;115:839-55) C1 [Shifren, Jan L.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Shifren, JL (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, 55 Fruit St,YAW 10A, Boston, MA 02114 USA. EM jshifren@partners.org FU Proctor & Gamble Pharmaceuticals (Cincinnati, Ohio) FX Dr. Shifren serves as a scientific advisory board member for the New England Research Institutes. She has been a research study consultant for Eli Lily & Co. (Indianapolis, Indiana) and Boehringer Ingelheim (Ingelheim, Germany). She also has received research support from Proctor & Gamble Pharmaceuticals (Cincinnati, Ohio). The other author did not report any potential conflicts of interest. NR 93 TC 33 Z9 33 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2010 VL 115 IS 4 BP 839 EP 855 DI 10.1097/AOG.0b013e3181d41191 PG 17 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 580QH UT WOS:000276463700024 PM 20308847 ER PT J AU Tsai, WL Chung, RT AF Tsai, W-L Chung, R. T. TI Viral hepatocarcinogenesis SO ONCOGENE LA English DT Review DE hepatocellular carcinoma; hepatitis B virus; hepatitis C virus; genomics; signaling pathways pathogenesis ID HEPATITIS-B-VIRUS; HCV CORE PROTEIN; NF-KAPPA-B; COMPARATIVE GENOMIC HYBRIDIZATION; NONSTRUCTURAL 5A PROTEIN; CHRONIC LIVER-DISEASE; HUMAN HEPATOCELLULAR-CARCINOMA; ENDOPLASMIC-RETICULUM STRESS; INDUCED OXIDATIVE STRESS; C-VIRUS AB Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Despite recent advances in the diagnosis and treatment of HCC, its prognosis remains dismal. Infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major risk factors for HCC. Although both are hepatotropic viral infections, there are important differences between the oncogenic mechanisms of these two viruses. In addition to the oncogenic potential of its viral proteins, HBV, as a DNA virus, can integrate into host DNA and directly transform hepatocytes. In contrast, HCV, an RNA virus, is unable to integrate into the host genome, and viral protein expression has a more critical function in hepatocarcinogenesis. Both HBV and HCV proteins have been implicated in disrupting cellular signal transduction pathways that lead to unchecked cell growth. Most HCC develops in the cirrhotic liver, but the linkage between cirrhosis and HCC is likely multifactorial. In this review, we summarize current knowledge regarding the pathogenetic mechanisms of viral HCC. Oncogene (2010) 29, 2309-2324; doi:10.1038/onc.2010.36; published online 15 March 2010 C1 [Tsai, W-L; Chung, R. T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. [Tsai, W-L] Kaohsiung Vet Gen Hosp, Dept Internal Med, Div Gastroenterol, Kaohsiung, Taiwan. RP Chung, RT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Dept Med, 55 Fruit St,Warren 1007, Boston, MA 02114 USA. EM rtchung@partners.org FU NIH [DK078772, AI069939] FX This work was supported by NIH Grants DK078772 and AI069939 (both to RTC). NR 234 TC 138 Z9 149 U1 1 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2010 VL 29 IS 16 BP 2309 EP 2324 DI 10.1038/onc.2010.36 PG 16 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 586YK UT WOS:000276951500001 PM 20228847 ER PT J AU Santo, L Vallet, S Hideshima, T Cirstea, D Ikeda, H Pozzi, S Patel, K Okawa, Y Gorgun, G Perrone, G Calabrese, E Yule, M Squires, M Ladetto, M Boccadoro, M Richardson, PG Munshi, NC Anderson, KC Raje, N AF Santo, L. Vallet, S. Hideshima, T. Cirstea, D. Ikeda, H. Pozzi, S. Patel, K. Okawa, Y. Gorgun, G. Perrone, G. Calabrese, E. Yule, M. Squires, M. Ladetto, M. Boccadoro, M. Richardson, P. G. Munshi, N. C. Anderson, K. C. Raje, N. TI AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3 beta activation and RNA polymerase II inhibition SO ONCOGENE LA English DT Article DE myeloma; cyclin-dependent kinase; GSK-3 beta; RNA pol II ID GLYCOGEN-SYNTHASE KINASE-3; DOWN-REGULATION; CELL-CYCLE; PROTEIN-KINASE; SELICICLIB CYC202; R-ROSCOVITINE; CANCER-CELLS; KAPPA-B; TRANSCRIPTION; SURVIVAL AB Dysregulated cell cycling is a universal hallmark of cancer and is often mediated by abnormal activation of cyclin-dependent kinases (CDKs) and their cyclin partners. Overexpression of individual complexes are reported in multiple myeloma (MM), making them attractive therapeutic targets. In this study, we investigate the preclinical activity of a novel small-molecule multi-CDK inhibitor, AT7519, in MM. We show the anti-MM activity of AT7519 displaying potent cytotoxicity and apoptosis; associated with in vivo tumor growth inhibition and prolonged survival. At the molecular level, AT7519 inhibited RNA polymerase II (RNA pol II) phosphorylation, a CDK9, 7 substrate, associated with decreased RNA synthesis confirmed by [(3)H] Uridine incorporation. In addition, AT7519 inhibited glycogen synthase kinase 3 beta (GSK-3 beta) phosphorylation; conversely pretreatment with a selective GSK-3 inhibitor and shRNA GSK-3 beta knockdown restored MM survival, suggesting the involvement of GSK-3 beta in AT7519-induced apoptosis. GSK-3 beta activation was independent of RNA pol II dephosphorylation confirmed by alpha-amanitin, a specific RNA pol II inihibitor, showing potent inhibition of RNA pol II phosphorylation without corresponding effects on GSK-3 beta phosphorylation. These results offer new insights into the crucial, yet controversial role of GSK-3 beta in MM and show significant anti-MM activity of AT7519, providing the rationale for its clinical evaluation in MM. Oncogene (2010) 29, 2325-2336; doi:10.1038/onc.2009.510; published online 25 January 2010 C1 [Santo, L.; Vallet, S.; Hideshima, T.; Cirstea, D.; Ikeda, H.; Pozzi, S.; Okawa, Y.; Gorgun, G.; Perrone, G.; Calabrese, E.; Richardson, P. G.; Munshi, N. C.; Anderson, K. C.; Raje, N.] Harvard Univ, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Sch Med, Boston, MA 02115 USA. [Vallet, S.; Pozzi, S.; Patel, K.; Raje, N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02115 USA. [Yule, M.; Squires, M.] Astex Therapeut Ltd, Cambridge, England. [Ladetto, M.; Boccadoro, M.] Univ Turin, Div Ematol, Turin, Italy. RP Santo, L (reprint author), Harvard Univ, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Sch Med, 44 Binney St, Boston, MA 02115 USA. EM loredana_santo@dfci.harvard.edu RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 FU ASCO CDA; Multiple Myeloma Research Foundation (MMRF); International Myeloma Foundation (IMF); Leukemia and Lymphoma Society FX This work was supported by ASCO CDA, Multiple Myeloma Research Foundation (MMRF), International Myeloma Foundation (IMF) and Leukemia and Lymphoma Society Clinical Scholar Award. NR 45 TC 52 Z9 53 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2010 VL 29 IS 16 BP 2325 EP 2336 DI 10.1038/onc.2009.510 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 586YK UT WOS:000276951500002 PM 20101221 ER PT J AU Lauring, J Cosgrove, DP Fontana, S Gustin, JP Konishi, H Abukhdeir, AM Garay, JP Mohseni, M Wang, GM Higgins, MJ Gorkin, D Reis, M Vogelstein, B Polyak, K Cowherd, M Buckhaults, PJ Park, BH AF Lauring, J. Cosgrove, D. P. Fontana, S. Gustin, J. P. Konishi, H. Abukhdeir, A. M. Garay, J. P. Mohseni, M. Wang, G. M. Higgins, M. J. Gorkin, D. Reis, M. Vogelstein, B. Polyak, K. Cowherd, M. Buckhaults, P. J. Park, B. H. TI Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations SO ONCOGENE LA English DT Article DE Akt1; oncogene; knock in; gene targeting; breast epithelial cells ID PLECKSTRIN HOMOLOGY DOMAIN; PTEN LOSS; PHOSPHOINOSITIDE 3-KINASE; HIGH-FREQUENCY; CANCER; ACTIVATION; CARCINOMA; GENE; CORRELATE; PATHWAY AB An oncogenic mutation (G49A:E17K) in the AKT1 gene has been described recently in human breast, colon, and ovarian cancers. The low frequency of this mutation and perhaps other selective pressures have prevented the isolation of human cancer cell lines that harbor this mutation thereby limiting functional analysis. Here, we create a physiologic in vitro model to study the effects of this mutation by using somatic cell gene targeting using the nontumorigenic human breast epithelial cell line, MCF10A. Surprisingly, knock in of E17K into the AKT1 gene had minimal phenotypic consequences and importantly, did not recapitulate the biochemical and growth characteristics seen with somatic cell knock in of PIK3CA hotspot mutations. These results suggest that mutations in critical genes within the PI3-kinase (PI3K) pathway are not functionally equivalent, and that other cooperative genetic events may be necessary to achieve oncogenic PI3K pathway activation in cancers that contain the AKT1 E17K mutation. Oncogene (2010) 29, 2337-2345; doi:10.1038/onc.2009.516; published online 25 January 2010 C1 [Lauring, J.; Cosgrove, D. P.; Fontana, S.; Gustin, J. P.; Konishi, H.; Abukhdeir, A. M.; Garay, J. P.; Mohseni, M.; Wang, G. M.; Higgins, M. J.; Gorkin, D.; Reis, M.; Vogelstein, B.; Park, B. H.] Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Baltimore, MD 21231 USA. [Polyak, K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cowherd, M.; Buckhaults, P. J.] Univ S Carolina, Sch Med, Columbia, SC USA. RP Lauring, J (reprint author), Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Sch Med, 1650 Orleans St,Room 146, Baltimore, MD 21231 USA. EM jlaurin1@jhmi.edu; bpark2@jhmi.edu RI Reis, Marcelo/H-9370-2012; OI Reis, Marcelo/0000-0002-4706-1041; Konishi, Hiroyuki/0000-0003-1131-4905; Lauring, Josh/0000-0002-4312-704X FU Flight Attendant Medical Research Institute (FAMRI); V Foundation; Maryland Cigarette Restitution Fund; National Institutes of Health [CA88843, CA088843-08, T32 CA09071-27, CA109274]; trust of Ruby J Nelson in loving memory of Charlotte R Nelson; Avon Foundation; American Society of Clinical Oncology Foundation; Department of Defense [W81XWH-06-1-0325, BC083057]; FAMRI; Susan G Komen Foundation; Medical Scientist Training Program Fellowship; Mary Kay Ash Charitable Foundation; Stewart Trust Fund; Breast Cancer Research Foundation FX JL receives support from the Flight Attendant Medical Research Institute (FAMRI), the V Foundation, and the Maryland Cigarette Restitution Fund, National Institutes of Health Grants CA88843, CA088843-08, The Susan G Komen for the Cure Career Catalyst Grant funded by the trust of Ruby J Nelson in loving memory of Charlotte R Nelson, and the Avon Foundation. DC receives support from National Institutes of Health Grant T32 CA09071-27 and a Young Investigator Award from the American Society of Clinical Oncology Foundation. JP Gustin is a recipient of a Department of Defense Breast Cancer Research Program Predoctoral Fellowship Award W81XWH-06-1-0325. JP Garay is a recipient of a Research Supplement to promote diversity in health-related research. HK is a recipient of a Young Clinical Scientist Award from FAMRI. AMA is supported by a Susan G Komen Foundation Postdoctoral Fellowship Award. GW is a recipient of a Medical Scientist Training Program Fellowship. MM is recipient of a Department of Defense Breast Cancer Predoctoral Training Award (BC083057). BHP acknowledges support from the Avon Foundation, Susan G Komen for the Cure, the Mary Kay Ash Charitable Foundation, the Stewart Trust Fund, National Institutes of Health Grants CA109274 and CA88843, FAMRI, and the Breast Cancer Research Foundation. NR 30 TC 26 Z9 26 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2010 VL 29 IS 16 BP 2337 EP 2345 DI 10.1038/onc.2009.516 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 586YK UT WOS:000276951500003 PM 20101210 ER PT J AU Ercan, D Zejnullahu, K Yonesaka, K Xiao, Y Capelletti, M Rogers, A Lifshits, E Brown, A Lee, C Christensen, JG Kwiatkowski, DJ Engelman, JA Janne, PA AF Ercan, D. Zejnullahu, K. Yonesaka, K. Xiao, Y. Capelletti, M. Rogers, A. Lifshits, E. Brown, A. Lee, C. Christensen, J. G. Kwiatkowski, D. J. Engelman, J. A. Jaenne, P. A. TI Amplification of EGFR T790M causes resistance to an irreversible EGFR inhibitor SO ONCOGENE LA English DT Article DE epidermal growth factor receptor; drug resistance; EGFR T790M; amplification; tyrosine kinase inhibitor; non-small cell lung cancer ID GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA; GASTROINTESTINAL STROMAL TUMOR; CHRONIC MYELOGENOUS LEUKEMIA; ACQUIRED-RESISTANCE; DRUG-RESISTANCE; NERATINIB HKI-272; GENE MUTATION AB Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib are effective therapies against mutant non-small cell lung cancers (NSCLCs). Treatment is limited by the development of resistance in part explained by the gain of a secondary EGFR mutation, T790M, at the gatekeeper residue. Irreversible EGFR inhibitors, including PF00299804, are effective in vitro and in vivo against EGFR mutant tumors that contain EGFR T790M and are currently under clinical development. In this study, we generate models of resistance to PF00299804, using cell lines with EGFR T790M and show that the PF00299804-resistant models develop focal amplification of EGFR that preferentially involves the T790M-containing allele. These PF00299804-resistant cell lines remain dependent on EGFR for growth as downregulation of EGFR by shRNA compromises their viability. We show that resistance to PF00299804 arises, at least in part, through selection of a pre-existing EGFR T790M-amplified clone both in vitro and using a xenograft model in vivo. Our findings show that EGFR T790M is a common resistance mechanism to both reversible, and when amplified, the irreversible EGFR kinase inhibitors further emphasizing the need to develop more potent therapies against EGFR T790M. These findings can be used to guide studies of patient tumor specimens from ongoing clinical trials of irreversible EGFR kinase inhibitors. Oncogene (2010) 29, 2346-2356; doi:10.1038/onc.2009.526; published online 1 February 2010 C1 [Ercan, D.; Zejnullahu, K.; Yonesaka, K.; Capelletti, M.; Rogers, A.; Jaenne, P. A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Ercan, D.; Zejnullahu, K.; Yonesaka, K.; Capelletti, M.; Rogers, A.; Jaenne, P. A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xiao, Y.; Lee, C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lifshits, E.; Engelman, J. A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Brown, A.] Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, Cambridge, MA 02138 USA. [Christensen, J. G.] Pfizer Global Res & Dev, Dept Res Pharmacol, La Jolla Labs, La Jolla, CA USA. [Kwiatkowski, D. J.] Brigham & Womens Hosp, Div Translat Med, Boston, MA 02115 USA. [Jaenne, P. A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D820,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org FU National Institutes of Health [RO1CA114465-04, R01CA135257-01, R01CA137008-01]; National Cancer Institute [P50CA090578]; American Cancer Society [RSG0610201]; Hazel and Samuel Bellin research fund FX Supported by grants from the National Institutes of Health RO1CA114465-04 (PAJ), R01CA135257-01 (PAJ, JAE, CL), R01CA137008-01 (JAE, PAJ), National Cancer Institute Lung SPORE P50CA090578 (PAJ, JAE and DJK), American Cancer Society RSG0610201CCE (PAJ, JAE), and the Hazel and Samuel Bellin research fund (PAJ). NR 44 TC 116 Z9 121 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2010 VL 29 IS 16 BP 2346 EP 2356 DI 10.1038/onc.2009.526 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 586YK UT WOS:000276951500004 PM 20118985 ER PT J AU Ahuero, AE Jakobiec, FA Bhat, P Ciralsky, JB Papaliodis, GN AF Ahuero, Audrey E. Jakobiec, Frederick A. Bhat, Pooja Ciralsky, Jessica B. Papaliodis, George N. TI Paraneoplastic Conjunctival Cicatrization: Two Different Pathogenic Types SO OPHTHALMOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; OCULAR INVOLVEMENT; PEMPHIGUS; MANIFESTATIONS; ASSOCIATION; DISEASE; CANCER AB Purpose: To describe the clinical and immunopathologic features of patients with 2 different types of paraneoplastic conjunctival cicatrization. Design: Retrospective observational case analyses with a review of the literature. Participants: One patient with paraneoplastic ocular cicatricial pemphigoid (POCP) and 1 patient with paraneoplastic pemphigus (PNP) with ocular involvement. Methods: Critical review of clinical history, diagnostic studies, and immunopathologic results of biopsies in the 2 cases, together with a review of the literature. Main Outcome Measures: Ability to recognize paraneoplastic conjunctival cicatrization and to diagnose the conditions accurately. Results: The first patient, 46 years of age, presented with conjunctival scarring and symblephara, cough, oral lesions, and chest rash. Concurrently, a diagnosis of pulmonary squamous cell carcinoma was made. Conjunctival biopsy revealed a subepithelial bulla, an inflammatory infiltrate of T and B lymphocytes, and basement membrane zone deposition of immunoglobulin (Ig)-G and C3 consistent with POCP. The second patient, 54 years of age, had a recently diagnosed B-cell chronic lymphocytic leukemia, followed 1 month later with ocular irritation and bilateral extensive symblephara. Extensive oral lesions and skin involvement of the lower half of the body were seen. Skin biopsy disclosed subepidermal bullae and mostly T cells with virtually no B cells in the dermal infiltrate (the patient was being treated with rituximab). Linear subepithelial deposition of IgG and C3 and deposition within the epidermis were consistent with PNP. Further indirect immunofluorescence and immunoprecipitation studies with the patient's serum-derived antibodies established PNP as the definitive diagnosis. Conclusions: Underlying malignancy is an important consideration in younger patients with puzzling bilateral cicatrizing conjunctivitis, and a paraneoplastic condition can be established from either a conjunctival or a skin biopsy. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2010;117:659-664 (C) 2010 by the American Academy of Ophthalmology. C1 [Ahuero, Audrey E.; Jakobiec, Frederick A.; Bhat, Pooja; Ciralsky, Jessica B.; Papaliodis, George N.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Bhat, Pooja] Massachusetts Eye & Ear Infirm, Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Ciralsky, Jessica B.] Massachusetts Eye & Ear Infirm, Cornea & External Dis Serv, Boston, MA 02114 USA. [Papaliodis, George N.] Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St,Suite 321, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 27 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2010 VL 117 IS 4 BP 659 EP 664 DI 10.1016/j.ophtha.2009.09.006 PG 6 WC Ophthalmology SC Ophthalmology GA 582YZ UT WOS:000276638800003 PM 20045572 ER PT J AU Tibbetts, MD Shah, CP Young, LH Duker, JS Maguire, JI Morley, MG AF Tibbetts, Michael D. Shah, Chirag P. Young, Lucy H. Duker, Jay S. Maguire, Joseph I. Morley, Michael G. TI Treatment of Acute Retinal Necrosis SO OPHTHALMOLOGY LA English DT Article ID FELLOW EYE INVOLVEMENT; ARN SYNDROME; MANAGEMENT; DETACHMENT; ACYCLOVIR; THERAPY; PHOTOCOAGULATION; VALACYCLOVIR AB Objectives: To compare outcomes from patients with acute retinal necrosis (ARN) treated in the acyclovir-only era with those treated in the era of newer antiviral therapies, identify variables affecting outcomes in ARN, and evaluate strategies for fellow eye prophylaxis. Design: Multicenter, nonrandomized, retrospective, interventional series. Participants: A cohort of 58 patients diagnosed with ARN by a retina specialist at 1 of 4 referral centers between 1981 and 2008. The cohort was divided into 2 subgroups: patients treated during the acyclovir-only era (n = 36) and patients treated during the current era of newer antiviral medications (n = 22). Intervention: Intravenous, oral, or intravitreal antiviral medications, including acyclovir, valacyclovir, famciclovir, valganciclovir, ganciclovir, and foscarnet; prophylactic laser retinopexy; aspirin; oral steroids. Main Outcome Measures: Visual acuity, retinal detachment, and fellow eye involvement. Results: A wide range and combination of antiviral agents are currently used for initial and long-term treatment of ARN. Outcomes from the newer antivirals era were similar to those achieved during the acyclovir-only era. In both groups, the incidence of 20/200 or worse visual acuity was 24% per person-year (P = 0.91). The prevalence of retinal detachment was approximately 50% in each group (P = 0.59). No variables, including prophylactic laser retinopexy, were associated with risk of retinal detachment. Two patients (3.4%) developed ARN in the initially unaffected eye. Conclusions: Current treatment trends vary widely, including single agents or combinations of oral, intravenous, and intravitreal agents. Differing strategies did not affect outcomes. The final visual acuity in ARN was generally poor. Retinal detachment was common and could neither be predicted nor prevented. Development of ARN in the unaffected fellow eye occurred rarely. Long-term oral antiviral treatment strategies varied with unclear relative efficacy. C1 [Morley, Michael G.] Ophthalm Consultants Boston, Boston, MA 02114 USA. [Tibbetts, Michael D.] Harvard Univ, Sch Med, Boston, MA USA. [Shah, Chirag P.; Maguire, Joseph I.] Wills Eye Hosp & Res Inst, Retina Serv, Philadelphia, PA USA. [Young, Lucy H.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Duker, Jay S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Morley, MG (reprint author), Ophthalm Consultants Boston, Suite 600,50 Staniford St, Boston, MA 02114 USA. EM mgmorley@eyeboston.com FU Center for Eye Research and Education FX Financial support: Center for Eye Research and Education. NR 30 TC 26 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2010 VL 117 IS 4 BP 818 EP 824 DI 10.1016/j.ophtha.2009.09.001 PG 7 WC Ophthalmology SC Ophthalmology GA 582YZ UT WOS:000276638800026 PM 20079537 ER PT J AU Vinegoni, C Feruglio, PF Cortez-Retamozo, V Razansky, D Medoff, BD Ntziachristos, V Sbarbati, A Pittet, M Weissleder, R AF Vinegoni, Claudio Feruglio, Paolo Fumene Cortez-Retamozo, Virna Razansky, Daniel Medoff, Benjamin D. Ntziachristos, Vasilis Sbarbati, Andrea Pittet, Mikael Weissleder, Ralph TI Imaging of molecular probe activity with Born-normalized fluorescence optical projection tomography SO OPTICS LETTERS LA English DT Article ID IN-VIVO AB Optical projection tomography is a new ex vivo imaging technique that allows imaging of whole organs in three dimensions at high spatial resolutions. In this Letter we demonstrate its capability to tomographically visualize molecular activity in whole organs of mice. In particular, eosinophil activity in asthmatic lungs is resolved using a Born-normalized fluorescence optical projection tomography and employing a near-IR molecular probe. The possibility to achieve molecularly sensitive imaging contrast in optical projection tomography by means of targeted and activatable imaging reporter agents adds a new range of capabilities for investigating molecular signatures of pathophysiological processes and a wide variety of diseases and their development. (C) 2010 Optical Society of America C1 [Vinegoni, Claudio; Feruglio, Paolo Fumene; Cortez-Retamozo, Virna; Pittet, Mikael; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Feruglio, Paolo Fumene; Sbarbati, Andrea] Univ Verona, Dept Morphol & Biomed Sci, I-37134 Verona, Italy. [Razansky, Daniel; Ntziachristos, Vasilis] Tech Univ Munich, IBMI, D-85764 Neuherberg, Germany. [Razansky, Daniel; Ntziachristos, Vasilis] Helmholtz Ctr Munich, D-85764 Neuherberg, Germany. [Medoff, Benjamin D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Charlestown, MA 02129 USA. [Medoff, Benjamin D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Vinegoni, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu OI Razansky, Daniel/0000-0001-8676-0964 FU National Institutes of Health (NIH) [1-RO1-EB006432]; Veneto Nanotech; CARIVERONA Foundation FX C. Vinegoni acknowledges support from the National Institutes of Health (NIH) grant 1-RO1-EB006432. We also acknowledge support from Veneto Nanotech and CARIVERONA Foundation. NR 11 TC 3 Z9 3 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD APR 1 PY 2010 VL 35 IS 7 BP 1088 EP 1090 PG 3 WC Optics SC Optics GA 578QP UT WOS:000276309300066 PM 20364226 ER PT J AU Thompson, GR Patel, PK Kirkpatrick, WR Westbrook, SD Berg, D Erlandsen, J Redding, SW Patterson, TF AF Thompson, George R., III Patel, Payal K. Kirkpatrick, William R. Westbrook, Steven D. Berg, Deborah Erlandsen, Josh Redding, Spencer W. Patterson, Thomas F. TI Oropharyngeal candidiasis in the era of antiretroviral therapy SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; FLUCONAZOLE-RESISTANT CANDIDA; IN-VITRO SUSCEPTIBILITY; ESOPHAGEAL CANDIDIASIS; DOUBLE-BLIND; REFRACTORY OROPHARYNGEAL; ORAL CANDIDIASIS; 1,3-BETA-D-GLUCAN SYNTHASE; CASPOFUNGIN RESISTANCE AB Oropharyngeal candidiasis (OPC) remains a common problem in the HIV-infected population despite the availability of antiretroviral therapy (ART). Although Candida albicans is the most frequently implicated pathogen, other Candida species also may cause infection. The emergence of antifungal resistance within these causative yeasts, especially in patients with recurrent oropharyngeal infection or with long-term use of antifungal therapies, requires a working knowledge of alternative antifungal agents. Identification of the infecting organism and antifungal susceptibility testing enhances the ability of clinicians to prescribe appropriate antifungal therapy. Characterization of the responsible mechanisms has improved our understanding of the development of antifungal resistance and could enhance the management of these infections. Immune reconstitution has been shown to reduce rates of OPC, but few studies have evaluated the current impact of ART on the epidemiology of OPC and antifungal resistance in these patients. Preliminary results from an ongoing clinical study showed that in patients with advanced AIDS, oral yeast colonization was extensive, occurring in 81.1% of the 122 patients studied, and symptomatic infection occurred in one-third. In addition, resistant yeasts were still common, occurring in 25.3% of patients colonized with yeasts or with symptomatic infection. Thus, OPC remains a significant infection in advanced AIDS, even with ART. Current knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and mechanisms of antifungal resistance observed in OPC are important in managing patients with this infection and are the focus of this review. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: 488-495) C1 [Thompson, George R., III; Patel, Payal K.; Kirkpatrick, William R.; Berg, Deborah; Erlandsen, Josh; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. [Thompson, George R., III; Westbrook, Steven D.; Redding, Spencer W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. [Westbrook, Steven D.; Redding, Spencer W.; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Thompson, GR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Internal Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM thompsong2@uthscsa.edu OI Patel, Payal/0000-0001-8666-7313 FU Basilea; Merck; Pfizer; Schering-Plough; Astellas; National Institute of Health [5RO1DE018096] FX G. R. T. has served as a consultant for Basilea. T. F. P. has received research support from Basilea, Merck, Pfizer, and Schering-Plough, has received speaking fees from Merck and Pfizer, and is a consultant for Basilea, Merck, Nektar, Pfizer, and Toyama. S. W. R. has received research support from Pfizer, Schering-Plough, and Astellas.; Supported in part by a National Institute of Health research grant to T. F. P. (5RO1DE018096). NR 63 TC 42 Z9 43 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 EI 1528-395X J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD APR PY 2010 VL 109 IS 4 BP 488 EP 495 DI 10.1016/j.tripleo.2009.11.026 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 571IT UT WOS:000275746200002 PM 20156694 ER PT J AU Napenas, JJ Brennan, MT Coleman, S Kent, ML Noll, J Frenette, G Nussbaum, ML Mougeot, JL Paster, BJ Lockhart, PB Bahrani-Mougeot, FK AF Napenas, Joel J. Brennan, Michael T. Coleman, Shirley Kent, M. Louise Noll, Jenene Frenette, Gary Nussbaum, Marcy L. Mougeot, Jean-Luc Paster, Bruce J. Lockhart, Peter B. Bahrani-Mougeot, Farah K. TI Molecular methodology to assess the impact of cancer chemotherapy on the oral bacterial flora: a pilot study SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ACUTE-LEUKEMIA; NEUTROPENIC PATIENTS; INDUCTION THERAPY; MUCOSITIS; MICROFLORA; BACTEREMIA; PATHOGENESIS; CHILDREN; CAVITY AB Objective. This pilot study determined the profile of the oral bacterial flora in an outpatient cancer population before and after chemotherapy using molecular techniques. Study design. We recruited 9 newly diagnosed breast cancer patients scheduled for induction chemotherapy. All were seen immediately before chemotherapy, and 7 to 14 days later. At both visits, we performed oral evaluations and obtained mucositis grading (with the World Health Organization [WHO] scale), absolute neutrophil counts (ANC), and bacterial samples from the buccal mucosa. Bacterial DNA was isolated, and 16S ribosomal RNA gene clonal libraries were constructed. Sequences of genes in the library were used to determine species identity by comparison to known sequences. Results. After chemotherapy, WHO scores of 0 and 1 were in 3 and 6 patients, respectively, and mean ANC (+/- SD) dropped from 3326 +/- 463 to 1091 +/- 1082 cells/mm(3). From pre- and post-chemotherapy samples, 41 species were detected, with a predominance of Gemella haemolysans and Streptococcus mitis. More than 85% of species have not been previously identified in chemotherapy patients. Seven species appeared exclusively before chemotherapy and 25 after chemotherapy. After chemotherapy, the number of species per patient increased by a mean of 2.6 (SD = 4.7, P = .052). Conclusion. We identified species not previously identified in chemotherapy patients. Our results suggest a shift to a more complex oral bacterial profile in patients undergoing cancer chemotherapy. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: 554-560) C1 [Napenas, Joel J.; Brennan, Michael T.; Coleman, Shirley; Kent, M. Louise; Noll, Jenene; Lockhart, Peter B.; Bahrani-Mougeot, Farah K.] Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28232 USA. [Coleman, Shirley; Mougeot, Jean-Luc; Bahrani-Mougeot, Farah K.] Carolinas Med Ctr, Cannon Res Ctr, Charlotte, NC 28232 USA. [Frenette, Gary] Carolinas Med Ctr, Dept Internal Med, Charlotte, NC 28232 USA. [Nussbaum, Marcy L.] Carolinas Med Ctr, Dickson Inst Hlth Sci, Charlotte, NC 28232 USA. [Paster, Bruce J.] Forsyth Inst, Boston, MA USA. RP Napenas, JJ (reprint author), Carolinas Med Ctr, Dept Oral Med, POB 32861, Charlotte, NC 28232 USA. EM joel.napenas@carolinashealthcare.org RI 段, 沛沛/C-9902-2010 FU Charlotte-Mecklenburg Health Services Foundation FX This study was supported by a grant from The Charlotte-Mecklenburg Health Services Foundation. NR 30 TC 14 Z9 16 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD APR PY 2010 VL 109 IS 4 BP 554 EP 560 DI 10.1016/j.tripleo.2009.11.015 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 571IT UT WOS:000275746200011 PM 20303053 ER PT J AU Friedlander, AH Sung, EC Chung, EM Garrett, NR AF Friedlander, Arthur H. Sung, Eric C. Chung, Evelyn M. Garrett, Neal R. TI Radiographic quantification of chronic dental infection and its relationship to the atherosclerotic process in the carotid arteries SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article ID INTIMA-MEDIA THICKNESS; PERIODONTAL-DISEASE; CARDIOVASCULAR-DISEASE; ATHEROMATOUS PLAQUES; GENDER-DIFFERENCES; ENDOTHELIAL-CELLS; HEART-DISEASE; TOOTH LOSS; CORONARY; RISK AB Background. Atherosclerosis may be initiated/accelerated by chronic dental infection (CDI). Noninvasively visualizing the carotid arteries is an accepted surrogate marker for determining coronary artery atherosclerosis (CAA). We hypothesized that 36 individuals with radiographic carotid atheromas would have more radiographic CDI than risk-matched individuals without atheromas. Methods. We determined the arithmetic sum of individuals' periapical and furcal lesions, pericoronitis sites, carious roots, teeth with pulpal caries, and vertical bony defects (> 4 mm). Results. Individuals with atheromas had a significantly (P < .01) greater mean score of 15.5 +/- 10.4 compared with control subjects (7.9 +/- 8.1). Similarly significant (P < .05) was the difference in the mean numbers of mesial and distal vertical bony defects in the atheroma group (4.1 +/- 3.9 and 4.8 +/- 3.8, respectively) compared with control subjects (1.6 +/- 2.4 and 1.8 +/- 2.7, respectively). Conclusions. Individuals with atheromas on their radiographs (and high probability of CAA) had significantly greater amounts of CDI than individuals without atheromas. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: 615-621) C1 [Friedlander, Arthur H.] Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. [Garrett, Neal R.] Univ Calif Los Angeles, Sch Dent, Weintraub Ctr Reconstruct Biotechnol, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 47 TC 9 Z9 9 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD APR PY 2010 VL 109 IS 4 BP 615 EP 621 DI 10.1016/j.tripleo.2009.10.036 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 571IT UT WOS:000275746200019 PM 20097109 ER PT J AU Shin, JJ Page, JH Shapiro, J Gray, ST Cunningham, MJ AF Shin, Jennifer J. Page, John H. Shapiro, Jo Gray, Stacey T. Cunningham, Michael J. TI Validation of a clinical practice ability instrument for surgical training SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation CY OCT 04-07, 2009 CL San Diego, CA SP Amer Acad Otolaryngol Head & Neck Surg Fdn ID OTOLARYNGOLOGY RESIDENTS; PROGRAM DIRECTORS; COMPETENCE; RELIABILITY; PERFORMANCE; ATTITUDES; LIFE AB OBJECTIVE: To develop and validate an instrument to measure the progression of clinical practice ability among surgical trainees. STUDY DESIGN: Prospective validation study. SETTING: Three academic training institutions: Massachusetts Eye and Ear Infirmary, Brigham and Women's Hospital, Harvard School of Public Health. SUBJECTS AND METHODS: A clinical practice instrument (CPI) was created and prospectively validated in otolaryngology trainees at three institutional sites. The instrument is completed during an oral examination of a trainee who is presented with a patient scenario; the scenario yields one clinical diagnosis, one therapeutic intervention, and one interventional complication. On the basis of the trainee's responses, 21 item scores are calculated focusing on key areas within the diagnostic and management paradigm. Internal consistency, reproducibility, inter-rater reliability, discriminant and criterion validity, and responsiveness to change over time were evaluated. RESULTS: There were 87 administrations of the instrument over a period of 22 months. The subjects (n = 32) spanned the range of training from medical student to clinical fellow. There was strong internal consistency within each domain (Cronbach's alpha 0.85-0.94, one-sided 95% confidence interval > 0.81). Inter-rater reliability was high (kappa 0.66, absolute agreement 72%). Reproducibility of item scores was excellent (intraclass correlation coefficient [ICC] final summary score 0.78, global item score 0.83). Discriminant validity (P < 0.0001), criterion validity (P = 0.03), and responsiveness to change (P = 0.0055) were also established. CONCLUSION: The CPI serves as a reliable, reproducible, and valid means to measure the progression of clinical practice ability in trainees as they transition from "novice" to "attending equivalent" surgeons. (C) 2010 American Academy of Otolaryngology Head and Neck Surgery Foundation. All rights reserved. C1 [Shin, Jennifer J.; Gray, Stacey T.; Cunningham, Michael J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Page, John H.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. [Shapiro, Jo] Harvard Univ, Brigham & Womens Hosp, Div Otolaryngol, Sch Med, Boston, MA 02114 USA. RP Shin, JJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM jennifer_shin@meei.harvard.edu RI Shin, Jennifer/A-3169-2016 NR 16 TC 2 Z9 2 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2010 VL 142 IS 4 BP 493 EP 499 DI 10.1016/j.otohns.2010.01.015 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 575MO UT WOS:000276071400004 PM 20304266 ER PT J AU Martinez-Alvernia, EA Mankarious, LA AF Martinez-Alvernia, Efrain A. Mankarious, Leila A. TI Matrix metalloproteinase inhibition causes luminal narrowing and ring thickening in the cricoid cartilage SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 24, 2009 CL Seattle, WA SP Amer Soc Pediat Otolaryngol ID TGF-BETA; EXPRESSION; PROTEASES; SITES AB OBJECTIVE: Luminal expansion of the cricoid cartilage appears to be stunted by loss of luminal epithelium (LE) and can be enhanced by transforming growth factor-beta 3 (TGF-beta 3). When both the LE and perichondrium are disrupted, matrix metalloproteinase (MMP) levels within adjacent chondrocytes are diminished but can be restored by exogenous TGF-beta 3. Cricoid growth stunting and luminal expansion that occur in the absence and presence of MMP activity, respectively, suggest that MMPs play an important role in normal subglottal development. The study objective was to determine if MMP inhibition affects cricoid expansion and by what mechanism, which will in turn help to define the mechanism of action of TGF-beta 3-induced luminal expansion. STUDY DESIGN: Ex vivo, in vitro whole organ culture of subglottises grown with and without the presence of an MMP inhibitor. SETTING: Tertiary care facility. SUBJECTS AND METHODS: Subglottises from 20 neonatal mice were divided into 10 grown with an MMP inhibitor, GM6001, and 10 grown in basic medium alone. The luminal cross-sectional area, apoptosis levels, cell proliferation rates, and presence or absence of cleaved aggrecan fragments were determined. RESULTS: Subglottises that were exposed to the MMP inhibitor displayed statistically significant luminal narrowing, accompanied by apparent circumferential thickening of the cricoid ring, relatively decreased apoptosis, increased chondrocyte proliferation, and decreased amounts of aggrecan cleavage fragments in the extracellular matrix. CONCLUSION: Matrix metalloproteinases likely play a significant role in growth of the cricoid cartilage such that their inhibition leads to marked changes in the shape of the ring. (C) 2010 American Academy of Otolaryngology Head and Neck Surgery Foundation. All rights reserved. C1 [Mankarious, Leila A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mankarious, LA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM leila_mankarious@meei.harvard.edu FU NHLBI NIH HHS [5K08HL070116] NR 14 TC 0 Z9 0 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2010 VL 142 IS 4 BP 510 EP 515 DI 10.1016/j.otohns.2009.12.044 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 575MO UT WOS:000276071400007 PM 20304269 ER PT J AU Nakajima, HH Dong, W Olson, ES Rosowski, JJ Ravicz, ME Merchant, SN AF Nakajima, Hideko Heidi Dong, Wei Olson, Elizabeth S. Rosowski, John J. Ravicz, Michael E. Merchant, Saumil N. TI Evaluation of Round Window Stimulation Using the Floating Mass Transducer by Intracochlear Sound Pressure Measurements in Human Temporal Bones SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Cochlea; Cochlear pressure; Floating mass transducer; Middle ear prosthesis; Round window; Stapes velocity; Temporal bone ID MIDDLE-EAR IMPLANT; INNER-EAR; HEARING; RECONSTRUCTION; TYMPANOPLASTY AB Hypothesis: Round window (RW) stimulation with a floating mass transducer (FMT) can be studied experimentally and optimized to enhance auditory transduction. Background: The FMT (MED-EL Vibrant Soundbridge) has been recently implanted in patients with refractory conductive or mixed hearing loss to stimulate the RW with varying degrees of success. The mechanics of RW stimulation with the FMT have not been studied in a systematic manner. Methods: In cadaveric human temporal bones, measurements of stapes velocity with laser vibrometry in response to FMT-RW stimulation were used to optimize FMT insertion. The effect of RW stimulation on hearing was estimated using simultaneous measurements of intracochlear pressures in both perilymphatic scalae with micro-optical pressure transducers. This enabled calculation of the differential pressure across the cochlear partition, which is directly tied to auditory transduction. Results: The best coupling between the FMT and RW was achieved with a piece of fascia placed between the RW and the FMT, and by "bracing" the free end of the FMT against the hypotympanic wall with dental impression material. FMT-RW stimulation provided differential pressures comparable with sound-induced oval window stimulation greater than 1 kHz. However, less than 1 kHz, the FMT was less capable. Conclusion: Measurements of stapes velocity and intracochlear sound pressures in scala vestibuli and scala tympani enabled experimental evaluation of FMT stimulation of the RW. The efficacy of FMT-RW coupling was influenced significantly by technical and surgical factors, which can be optimized. This temporal bone preparation also lays the foundation for future studies to investigate multiple issues of relevance to both basic and clinical science such as RW stimulation in stapes fixation, nonaerated middle ears, and third-window lesions, and to answer basic questions regarding bone conduction. C1 [Nakajima, Hideko Heidi; Rosowski, John J.; Ravicz, Michael E.; Merchant, Saumil N.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Nakajima, Hideko Heidi; Rosowski, John J.; Merchant, Saumil N.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Dong, Wei; Olson, Elizabeth S.] Columbia Univ, Dept Otolaryngol Head & Neck Surg, New York, NY USA. [Rosowski, John J.; Ravicz, Michael E.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Rosowski, John J.; Merchant, Saumil N.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Nakajima, HH (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM heidi_nakajima@meei.harvard.edu FU NIDCD NIH HHS [R01 DC003130, R01 DC004798, R01 DC004798-09, R01 DC004798-09S1, R01 DC04798, T32 DC00020, T32 DC000020] NR 16 TC 48 Z9 52 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD APR PY 2010 VL 31 IS 3 BP 506 EP 511 DI 10.1097/MAO.0b013e3181c0ea9f PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 581WE UT WOS:000276555200021 PM 19841600 ER PT J AU Mukerji, S Lee, DJ AF Mukerji, Sudeep Lee, Daniel J. TI De Visione, Voce et Auditu: The Contribution of Hieronymous Fabricius to Our Understanding of Tensor Tympani Function SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Otolaryngology-Historical-Society CY SEP 17, 2007 CL Alexandria, VA SP Otolaryngol Hist Soc DE Acoustic reflex; Eustachian tube; Impedance; Middle ear muscle; Stapedius ID VELI PALATINI; MUSCLES; REFLEX AB Study Design: This work reviews the literature concerning the life and scientific contributions of Hieronymous Fabricius (1533-1619). We also analyze the translated Latin text that focuses on the middle ear muscles from a first edition of Fabricius' book entitled De Visione, Voce et Auditu (The Vision, Voice and Hearing, 1600). Results: Hieronymous Fabricius was one of the first scientists to introduce structure-function relationships in anatomic research. Better known for his descriptions of venous valves and human fetal development, his major contribution to otology was his theory on tensor tympani (TT) function. The TT is 1 of 2 middle ear muscles whose function has undergone a long period of speculation since its discovery by Vesalius (1514-1564) and description by Eustachius (1510-1574). Fabricius' theory of TT physiology was described in his treatise De Visione, Voce et Auditu (1600). He wrote that the TT "protected" the tympanic membrane and helped in middle ear ventilation. In the 20th century, the development of the acoustic impedance measuring bridge by Otto Metz (1905-1993) allowed for the first objective measurements of middle ear function. Experiments on human subjects with various ear pathologies confirmed that the stapedius was the dominant sound evoked middle ear muscle. However, Fabricius' original theory on the TT's role in middle ear ventilation persists to this day based on recent physiologic, embryologic, and histologic studies. Conclusion: Hieronymous Fabricius was a pioneer in approaching anatomy from a structure-function relationship, and was an active proponent for maximizing the learning environment for students. Fabricius' writings provided the foundation for contemporary theories on the role of the TT, and he proposed those ideas during an era when great strides were being made to increase our understanding of ear anatomy and physiology. C1 [Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu FU NIDCD NIH HHS [K08 DC06285] NR 27 TC 1 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD APR PY 2010 VL 31 IS 3 BP 536 EP 543 DI 10.1097/MAO.0b013e3181bc35b3 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 581WE UT WOS:000276555200026 PM 20357631 ER PT J AU Fritz, S Fernandez-del Castillo, C Iafrate, AJ Mino-Kenudson, M Neyhard, N LaFemina, J Stirman, A Warshaw, AL Thayer, SP AF Fritz, Stefan Fernandez-del Castillo, Carlos Iafrate, A. John Mino-Kenudson, Mari Neyhard, Nancy LaFemina, Jennifer Stirman, Amy Warshaw, Andrew L. Thayer, Sarah P. TI Novel Xenograft and Cell Line Derived From an Invasive Intraductal Papillary Mucinous Neoplasm of the Pancreas Give New Insights Into Molecular Mechanisms SO PANCREAS LA English DT Article DE intraductal papillary mucinous neoplasms; pancreas; xenograft; cell line; genetic characterization ID LONG-TERM SURVIVAL; CLINICOPATHOLOGICAL CHARACTERISTICS; DUCTAL ADENOCARCINOMA; SYMPTOMATIC PATIENTS; UPDATED EXPERIENCE; CYSTIC NEOPLASMS; IN-SITU; RESECTION; TUMORS; CARCINOMAS AB Objectives: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are a unique entity with malignant potential. Histologically, pancreatic ductal adenocarcinoma (PDAC) arising in IPMN (intraductal papillary mucinous carcinoma [IPMC]) appears similar to sporadic PDAC; biologically, however, IPMC seems to have a less aggressive clinical course. Little is known about the genetic signature of IPMC. In this study, we describe a novel xenograft model and cell culture created to biologically and genetically characterize these tumors. Methods: Xenograft mice and cell lines were created from IPMC. Global genomic changes were evaluated by cytogenetic analysis and array comparative genomic hybridization. Specific mutations and sonic hedgehog (Shh) pathway activity were examined and xenografts evaluated for sensitivity to anti-Shh therapy. Results: Cytogenetic analysis showed a tetraploid karyotype with multiple aberrations. KRAS and p53 mutations and overexpression of the Shh pathway were identified. Array comparative genomic hybridization revealed multiple chromosomal aberrations comparable with previously published data in IPMNs. Murine xenograft tumors were sensitive to anti-Shh treatment. Conclusions: Characterization of IPMC cell lines and xenografts reveals similarities to previously published data on IPMN. In comparison to PDAC, moreover, these data reveal shared aberrations and distinct genomic changes. Thus, these xenograft model and cell lines may be useful for future preclinical investigations. C1 [Fritz, Stefan; Fernandez-del Castillo, Carlos; Neyhard, Nancy; LaFemina, Jennifer; Stirman, Amy; Warshaw, Andrew L.; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Iafrate, A. John; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Thayer, SP (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WAC 460, Boston, MA 02114 USA. EM sthayer@partners.org FU Karin Grunebaum Cancer Research Foundation; German Research Foundation; Marshall K. Bartlett Fellowship; American College of Surgeons; National Institutes of Health; National Cancer Institute/National Institute of Health [P30CA00651] FX This work was supported by funding from the Karin Grunebaum Cancer Research Foundation (S. F.), the German Research Foundation (S. F.), the Marshall K. Bartlett Fellowship (J. L.), the American College of Surgeons Clowes Award, and the National Institutes of Health (S. P. T.) and by research grant P30CA00651 from the National Cancer Institute/National Institute of Health. NR 37 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD APR PY 2010 VL 39 IS 3 BP 308 EP 314 DI 10.1097/MPA.0b013e3181bd5c10 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 573YY UT WOS:000275955500004 PM 19924021 ER PT J AU Hui, HX Tang, YMG Zhu, LJ Khoury, N Hui, Z Wang, KY Perfetti, R Go, VLW AF Hui, Hongxiang Tang, Yongming G. Zhu, Lunjian Khoury, Nasif Hui, Zhe Wang, Kevin Yuqi Perfetti, Ricardo Go, Vay Liang W. TI Glucagon Like Peptide-1-Directed Human Embryonic Stem Cells Differentiation Into Insulin-Producing Cells Via Hedgehog, cAMP, and PI3K Pathways SO PANCREAS LA English DT Article DE glucagonlike peptide-1 (GLP-1); embryonic stem cells; signal pathways ID IN-VITRO DIFFERENTIATION; PANCREAS DEVELOPMENT; PROTEIN-KINASE; REGULATED EXPRESSION; SIGNALING PATHWAYS; RESPONSE ELEMENT; SECRETING CELLS; GENE-EXPRESSION; SONIC HEDGEHOG; BONE-MARROW AB Objectives: That glucagonlike peptide-1 (GLP-1) induces differentiation of primate embryonic stem (ES) cells into insulin-producing cells has been reported by several groups and also confirmed with our observations. Methods: To further elucidate the process in detail and the signaling pathways involved in this differentiation, we induced human ES cells HUES1 differentiated into insulin secretion cells by GLP-1 treatment. Results: A time-dependent pattern of down expression of the stem cell markers (human telomerase reverse transcriptase and octamer-4), and the appearance of multiple A-cell-specific proteins (insulin, glucokinase, glucose transporter, type 2, and islet duodenal homeobox 1) and hedgehog signal molecules (Indian hedgehog, sonic hedgehog, and hedgehog receptor, patched) have been identified. Cotreatment with hedgehog signal inhibitor cytopamine was able to block this differentiation, providing evidence of the involvement of the hedgehog signaling pathway in GLP-1-induced differentiation. We also observed increased transcripts of the transcription factors of activator protein 1, serum response element-1, DNA-binding transcription factors, and cAMP response element in GLP-1-induced ES cell differentiation. Inhibition profile by its specific inhibitors indicated that the cyclic adenosine monophosphate and phosphatidylinositol-3-kinase pathways, but not the mitogen-activated protein kinase pathway, were required for the induced differentiation of ES cells. Conclusions: These data support that GLP-1 directs human ES cell differentiation into insulin-producing cells via hedgehog, cyclic adenosine monophosphate, and phosphatidylinositol-3-kinase pathways. C1 [Hui, Hongxiang; Hui, Zhe; Wang, Kevin Yuqi; Go, Vay Liang W.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Excellence Pancreat Dis, Los Angeles, CA 90024 USA. [Hui, Hongxiang] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Hui, Hongxiang; Zhu, Lunjian; Khoury, Nasif; Perfetti, Ricardo] Cedars Sinai Med Ctr, Div Endocrinol & Diabet, Los Angeles, CA 90048 USA. [Hui, Hongxiang; Tang, Yongming G.] Nanfang Med Univ, Int Ctr Metab Dis, Guangzhou, Guangdong, Peoples R China. [Tang, Yongming G.] Cedars Sinai Med Ctr, Div Med Genet, Los Angeles, CA 90048 USA. RP Hui, HX (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Excellence Pancreat Dis, Los Angeles, CA 90024 USA. EM huihongx@gmail.com FU National Institutes of Health [PO1AT003960]; Hirshberg Foundation for Pancreatic Cancer Research FX This work was partially supported by the National Institutes of Health funding of the UCLA Center of Excellence in Pancreatic Diseases (PO1AT003960) and the Hirshberg Foundation for Pancreatic Cancer Research. NR 55 TC 12 Z9 16 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD APR PY 2010 VL 39 IS 3 BP 315 EP 322 DI 10.1097/MPA.0b013e3181bc30dd PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 573YY UT WOS:000275955500005 PM 19924023 ER PT J AU Osborn, CY Egede, LE AF Osborn, Chandra Y. Egede, Leonard E. TI Validation of an Information-Motivation-Behavioral Skills model of diabetes self-care (IMB-DSC) SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Diabetes; Self-care; Behavior change; Social support; Motivation ID BLOOD-GLUCOSE CONTROL; COMPLICATIONS; MANAGEMENT; ADHERENCE; EDUCATION; SAMPLE; RISK AB Objective: Comprehensive behavior change frameworks are needed to provide guidance for the design, implementation, and evaluation of diabetes self-care programs in diverse populations. We applied the Information-Motivation-Behavioral Skills (IMB) model, a well-validated, comprehensive health behavior change framework, to diabetes self-care. Methods: Patients with diabetes were recruited from an outpatient clinic. Information gathered pertained to demographics, diabetes knowledge (information); diabetes fatalism (personal motivation); social support (social motivation); and diabetes self-care (behavior). Hemoglobin MC values were extracted from the patient medical record. Structural equation models tested the IMB framework. Results: More diabetes knowledge (r = 0.22 p < 0.05), less fatalistic attitudes (r = 0.20, p < 0.05), and more social support (r = 0.27, p < 0.01) were independent, direct predictors of diabetes self-care behavior; and through behavior, were related to glycemic control (r = 0.20, p <0.05). Conclusions: Consistent with the IMB model, having more information (more diabetes knowledge), personal motivation (less fatalistic attitudes), and social motivation (more social support) was associated with behavior: and behavior was the sole predictor of glycemic control. Practice implications: The IMB model is an appropriate, comprehensive health behavior change framework for diabetes self-care. The findings indicate that in addition to knowledge, diabetes education programs should target personal and social motivation to effect behavior change. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Osborn, Chandra Y.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Osborn, Chandra Y.] Vanderbilt Univ, Sch Med, Diabet Res & Training Ctr, Vanderbilt Eskind Diabet Ctr, Nashville, TN 37212 USA. [Osborn, Chandra Y.] Univ Connecticut, Ctr Hlth Intervent & Prevent, Storrs, CT USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Div Populat, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK [P60DK020593] FX Dr. Osborn is supported by a Minority Supplement Award (NIDDK P60DK020593). NR 31 TC 38 Z9 40 U1 1 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD APR PY 2010 VL 79 IS 1 BP 49 EP 54 DI 10.1016/j.pec.2009.07.016 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 583RW UT WOS:000276698200009 PM 19699601 ER PT J AU Quintiliani, L Allen, J Marino, M Kelly-Weeder, S Li, Y AF Quintiliani, Lisa Allen, Jennifer Marino, Miguel Kelly-Weeder, Susan Li, Yi TI Multiple health behavior clusters among female college students SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE College students; Female; Multiple behaviors; Cluster analysis ID PHYSICAL-ACTIVITY; RISK BEHAVIORS; UNITED-STATES; INTERVENTIONS; ADOLESCENT; ADULTHOOD; LIFE; CARE AB Objective: To examine prevalence of multiple unhealthful behaviors and detect clusters of unhealthful behaviors among college women. Methods: Women ages 18-22 enrolled full-time at an urban university located in the Northeastern United States were invited to complete an online survey, which assessed maintenance behaviors: fruits/ vegetables, physical activity, cervical screening and at-risk behaviors: frequent drinking, smoking, and non-use of protective measures during sexual intercourse. Of 4774 invited, complete data is available for 1463 participants (1463/4774 = 30.6%). Results: Nearly 65% had two or more unhealthful behaviors. Three distinct clusters were defined: cluster one included women who were lower in health maintenance and higher in at-risk behaviors; cluster two included women who were lower in health maintenance and lower in at-risk behaviors; and cluster three included women who were higher in health maintenance and intermediate in at-risk behaviors. Conclusion: These clustering patterns suggest health programs directed at college students address multiple behaviors simultaneously. Practice implications: Programs targeting multiple behaviors should consider activities for those seen within and outside of the context of health services. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Quintiliani, Lisa; Allen, Jennifer] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Quintiliani, Lisa; Allen, Jennifer] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Allen, Jennifer; Kelly-Weeder, Susan] Boston Coll, William F Connell Sch Nursing, Boston, MA USA. [Marino, Miguel; Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Quintiliani, L (reprint author), Boston Med Ctr, Med Informat Syst Unit, 801 Massachusetts Ave, Boston, MA 02118 USA. EM lisa.quintiliani@bmc.org RI Allen, Jennifer/M-2113-2015; OI Quintiliani, Lisa/0000-0002-3328-6768 NR 26 TC 16 Z9 17 U1 1 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD APR PY 2010 VL 79 IS 1 BP 134 EP 137 DI 10.1016/j.pec.2009.08.007 PG 4 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 583RW UT WOS:000276698200023 PM 19767168 ER PT J AU Hauer, J AF Hauer, Julie TI Identifying and Managing Sources of Pain and Distress in Children with Neurological Impairment SO PEDIATRIC ANNALS LA English DT Article ID COGNITIVE IMPAIRMENTS; NONCOMMUNICATING CHILDREN; CEREBRAL-PALSY; DOUBLE-BLIND; CASE SERIES; GABAPENTIN; SPASTICITY; FUNDOPLICATION; HYPOTHERMIA; VALIDATION C1 [Hauer, Julie] Dana Farber Canc Inst, Div Pediat Palliat Care, Boston, MA 02115 USA. RP Hauer, J (reprint author), 44 Binney St, Boston, MA 02115 USA. EM julie_hauer@dfci.harvard.edu NR 40 TC 10 Z9 10 U1 0 U2 5 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD APR PY 2010 VL 39 IS 4 BP 198 EP 205 DI 10.3928/00904481-20100318-04 PG 8 WC Pediatrics SC Pediatrics GA 580UZ UT WOS:000276477300005 PM 20411897 ER PT J AU Zacharoulis, S Chi, S Kadota, R Kieran, M AF Zacharoulis, Stergios Chi, Susan Kadota, Richard Kieran, Mark TI Biological Modification Strategies Following Marrow Ablative, High-Dose Chemotherapy (HDCT) With Autologous Hematopoietic Stem Cell Rescue (AHSCR) for Pediatric Brain Tumors SO PEDIATRIC BLOOD & CANCER LA English DT Review DE angiogenesis; autologous hematopoietic stem cell rescue; high-dose chemotherapy; pediatric brain tumors; retinoic acid ID PHASE-I TRIAL; RECURRENT MALIGNANT GLIOMAS; METRONOMIC CHEMOTHERAPY; 13-CIS-RETINOIC ACID; CANCER; ANGIOGENESIS; NEUROBLASTOMA; CHILDREN AB Maintenance biology-based therapy following HDCT/AHSCR in pediatric brain tumors has not been tested as yet. Failure of the HDCT/AHSCR might be due to tumor-immunity dysregulation, reactivation of the angiogenic switch and other mechanisms Angiogenesis has been shown to be reactivated following chemotherapy. The angiogenic factors engaged in this process in childhood brain tumors following HDCT/AHSCR have not been tested in the clinic. Metronomic chemotherapy has been found to be safe and angiogenesis inhibitors are currently tested in children. Other good possible candidates for clinical trials in this setting include retinoic acid and immunotherapy. Pediatr Blood Cancer 2010,54 654-656 (C) 2010 Wiley-Liss, Inc C1 [Zacharoulis, Stergios] Royal Marsden Hosp, Dept Pediat Oncol, Sutton SM2 5PT, Surrey, England. [Chi, Susan; Kieran, Mark] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Chi, Susan; Kieran, Mark] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [Kadota, Richard] Rady Childrens Hosp San Diego, Div Pediat Hematol Oncol, San Diego, CA USA. RP Zacharoulis, S (reprint author), Royal Marsden Hosp, Dept Pediat, Downs Rd, Sutton SM2 5PT, Surrey, England. OI Kieran, Mark/0000-0003-2184-7692 NR 16 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2010 VL 54 IS 4 BP 654 EP 656 DI 10.1002/pbc.22380 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 562GU UT WOS:000275038900040 PM 20146216 ER PT J AU Kesselheim, JC Johnson, J Joffe, S AF Kesselheim, Jennifer C. Johnson, Judith Joffe, Steven TI Ethics Consultation in Children's Hospitals: Results From a Survey of Pediatric Clinical Ethicists SO PEDIATRICS LA English DT Article DE ethics ID NATIONAL-SURVEY; GOALS AB OBJECTIVES: Ethics consultation is a widely endorsed mechanism for resolving conflict, facilitating communication, and easing moral distress in health care. Although ethics consultation has been well characterized in the adult setting, little is known about ethics consultation or ethics programs in pediatrics. We conducted a national survey of ethicists at freestanding children's hospitals to explore the structures and processes of their ethics-consultation services and committees and to characterize their training and professional activities. METHODS: We contacted freestanding children's hospitals from the member list of the National Association of Children's Hospitals and Related Institutions (N = 46) to identify the ethics leader at each institution. This individual was invited to complete an on-line survey instrument. The survey asked about ethicists' training to fulfill their ethics-related roles, their policies and methods for ethics consultation, and the structure and funding of their ethics committees. Thirty-three ethicists (72%) responded. RESULTS: On-the-job experience (73%) was the most frequently reported form of training; a minority of ethicists endorsed each other type of training. Although 60% of the respondents reported having a policy for ethics consultation, several elements recommended by national consensus statements were inconsistently included. In addition, respondents reported variable adherence to standard components of the consultation process, including meeting with the patient or family, following up with the clinical team, and providing a written report of the consultation. A minority of respondents reported having salary support (33%), administrative support (46%), or a budget (24%) for their work in ethics. CONCLUSIONS: Although ethics-consultation policies and practices at freestanding children's hospitals are generally well aligned with published norms, our data reveal imperfect adherence to consensus standards. Additional research is needed to determine how this practice variation, as well as the lack of salary support, budgets, and administrative assistance, affect the quality of ethics consultation at these institutions. Pediatrics 2010;125:742-746 C1 [Kesselheim, Jennifer C.; Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kesselheim, Jennifer C.; Joffe, Steven] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Johnson, Judith] Childrens Hosp, Off Eth, Boston, MA 02115 USA. RP Kesselheim, JC (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM jennifer_kesselheim@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 NR 13 TC 10 Z9 10 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2010 VL 125 IS 4 BP 742 EP 746 DI 10.1542/peds.2009-1813 PG 5 WC Pediatrics SC Pediatrics GA 577QR UT WOS:000276239600019 PM 20194289 ER PT J AU Ross, J Czernichow, P Biller, BMK Colao, A Reiter, E Kiess, W AF Ross, Judith Czernichow, Paul Biller, Beverly M. K. Colao, Annamaria Reiter, Ed Kiess, Wieland TI Growth Hormone: Health Considerations Beyond Height Gain SO PEDIATRICS LA English DT Article DE growth hormone; body composition; metabolism; safety ID FOR-GESTATIONAL-AGE; BONE-MINERAL DENSITY; IDIOPATHIC SHORT STATURE; GH-DEFICIENT PATIENTS; PRADER-WILLI-SYNDROME; INTIMA-MEDIA THICKNESS; CHRONIC-RENAL-FAILURE; QUANTITATIVE COMPUTED-TOMOGRAPHY; LEFT-VENTRICULAR DIMENSIONS; 6-YEAR FOLLOW-UP AB The therapeutic benefit of growth hormone (GH) therapy in improving height in short children is widely recognized; however, GH therapy is associated with other metabolic actions that may be of benefit in these children. Beneficial effects of GH on body composition have been documented in several different patient populations as well as improvements in lipid profile. Marked augmentation of bone mineral density also seems evident in many pediatric populations. Some of these benefits may require continued therapy past the acquisition of adult height. With long-term therapy of any kind, the adverse consequences of treatment should also be considered. Fortunately, long-term GH treatment seems to be safe and well-tolerated. This review describes the long-term metabolic effects of GH treatment in the pediatric population and considers how these may benefit children who are treated with GH. Pediatrics 2010; 125: e906-e918 C1 [Ross, Judith; Reiter, Ed] Thomas Jefferson Univ, Dept Pediat, Philadelphia, PA 19107 USA. [Czernichow, Paul] Hop Necker Enfants Malad, Dept Pediat Endocrinol & Diabet, Paris, France. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Colao, Annamaria] Univ Naples Federico II, Dept Mol & Clin Endocrinol & Oncol, Naples, Italy. [Reiter, Ed] Baystate Childrens Hosp, Dept Pediat, Springfield, MA USA. [Kiess, Wieland] Univ Leipzig, Dept Women & Child Hlth, Hosp Children & Adolescents, Leipzig, Germany. RP Ross, J (reprint author), Thomas Jefferson Univ, Dept Pediat, 1025 Walnut St,Suite 726, Philadelphia, PA 19107 USA. EM judith.ross@jefferson.edu NR 128 TC 19 Z9 20 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD APR PY 2010 VL 125 IS 4 BP E906 EP E918 DI 10.1542/peds.2009-1783 PG 13 WC Pediatrics SC Pediatrics GA 577QR UT WOS:000276239600061 PM 20308212 ER PT J AU Rudders, SA Banerji, A Corel, B Clark, S Camargo, CA AF Rudders, Susan A. Banerji, Aleena Corel, Blanka Clark, Sunday Camargo, Carlos A., Jr. TI Multicenter Study of Repeat Epinephrine Treatments for Food-Related Anaphylaxis SO PEDIATRICS LA English DT Article DE food allergy; anaphylaxis; emergency department; epinephrine ID EMERGENCY-DEPARTMENT VISITS; CHILDREN; ALLERGY; EPIDEMIOLOGY; COMMUNITY; EPIPEN AB OBJECTIVE: We sought to establish the frequency of receiving >1 dose of epinephrine in children who present to the emergency department (ED) with food-related anaphylaxis. PATIENTS AND METHODS: We performed a medical chart review at Boston hospitals of all children presenting to the ED for food-related acute allergic reactions between January 1, 2001, and December 31, 2006. We focused on causative foods, clinical presentations, and emergency treatments. RESULTS: Through random sampling and appropriate weighting, the 605 reviewed cases represented a study cohort of 1255 patients. These patients had a median age of 5.8 years (95% confidence interval [CI]: 5.3-6.3), and the cohort was 62% male. A variety of foods provoked the allergic reactions, including peanuts (23%), tree nuts (18%), and milk (15%). Approximately half (52% [95% CI: 48-57]) of the children met diagnostic criteria for food-related anaphylaxis. Among those with anaphylaxis, 31% received 1 dose and 3% received >1 dose of epinephrine before their arrival to the ED. In the ED, patients with anaphylaxis received antihistamines (59%), corticosteroids (57%), epinephrine (20%). Over the course of their reaction, 44% of patients with food-related anaphylaxis received epinephrine, and among this subset of patients, 12% (95% CI: 9-14) received >1 dose. Risk factors for repeat epinephrine use included older age and transfer from an outside hospital. Most patients (88%) were discharged from the hospital. On ED discharge, 43% were prescribed self-injectable epinephrine, and only 22% were referred to an allergist. CONCLUSIONS: Among children with food-related anaphylaxis who received epinephrine, 12% received a second dose. Results of this study support the recommendation that children at risk for food-related anaphylaxis carry 2 doses of epinephrine. Pediatrics 2010; 125: e711-e718 C1 [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, Boston, MA 02114 USA. [Rudders, Susan A.] Childrens Hosp, Div Allergy & Immunol, Boston, MA 02115 USA. [Banerji, Aleena; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. [Clark, Sunday] Univ Pittsburgh, Dept Med, Med Ctr, Pittsburgh, PA USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU Dey; National Institutes of Health (NIH) [NRSA T32-AI-007512] FX Dr Camargo has consulted for Dey (Napa, CA) and is principal investigator of an investigator-initiated research grant from Dey that partly supported the present study; the other authors have indicated they have no financial relationships relevant to this article to disclose.; Dr Rudders is supported by National Institutes of Health training grant NRSA T32-AI-007512. NR 24 TC 55 Z9 55 U1 1 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2010 VL 125 IS 4 BP E711 EP E718 DI 10.1542/peds.2009-2832 PG 8 WC Pediatrics SC Pediatrics GA 577QR UT WOS:000276239600036 PM 20308215 ER PT J AU Shen, YP Dies, KA Holm, IA Bridgemohan, C Sobeih, MM Caronna, EB Miller, KJ Frazier, JA Silverstein, I Picker, J Weissman, L Raffalli, P Jeste, S Demmer, LA Peters, HK Brewster, SJ Kowalczyk, SJ Rosen-Sheidley, B McGowan, C Duda, AW Lincoln, SA Lowe, KR Schonwald, A Robbins, M Hisama, F Wolff, R Becker, R Nasir, R Urion, DK Milunsky, JM Rappaport, L Gusella, JF Walsh, CA Wu, BL Miller, DT AF Shen, Yiping Dies, Kira A. Holm, Ingrid A. Bridgemohan, Carolyn Sobeih, Magdi M. Caronna, Elizabeth B. Miller, Karen J. Frazier, Jean A. Silverstein, Iris Picker, Jonathan Weissman, Laura Raffalli, Peter Jeste, Shafali Demmer, Laurie A. Peters, Heather K. Brewster, Stephanie J. Kowalczyk, Sara J. Rosen-Sheidley, Beth McGowan, Caroline Duda, Andrew W., III Lincoln, Sharyn A. Lowe, Kathryn R. Schonwald, Alison Robbins, Michael Hisama, Fuki Wolff, Robert Becker, Ronald Nasir, Ramzi Urion, David K. Milunsky, Jeff M. Rappaport, Leonard Gusella, James F. Walsh, Christopher A. Wu, Bai-Lin Miller, David T. CA Autism Consortium Clinical TI Clinical Genetic Testing for Patients With Autism Spectrum Disorders SO PEDIATRICS LA English DT Article DE array CGH; aCGH; autism spectrum disorder; ASD; language delay; microdeletion; microduplication; neuropsychiatric disorders ID PERVASIVE DEVELOPMENTAL DISORDERS; COMPARATIVE GENOMIC HYBRIDIZATION; MENTAL-RETARDATION; COPY-NUMBER; ARRAY-CGH; CHROMOSOMAL REARRANGEMENTS; FISH ANALYSIS; CHILDREN; IMBALANCES; MICROARRAY AB BACKGROUND: Multiple lines of evidence indicate a strong genetic contribution to autism spectrum disorders (ASDs). Current guidelines for clinical genetic testing recommend a G-banded karyotype to detect chromosomal abnormalities and fragile X DNA testing, but guidelines for chromosomal microarray analysis have not been established. PATIENTS AND METHODS: A cohort of 933 patients received clinical genetic testing for a diagnosis of ASD between January 2006 and December 2008. Clinical genetic testing included G-banded karyotype, fragile X testing, and chromosomal microarray (CMA) to test for submicroscopic genomic deletions and duplications. Diagnostic yield of clinically significant genetic changes was compared. RESULTS: Karyotype yielded abnormal results in 19 of 852 patients (2.23% [95% confidence interval (CI): 1.73%-2.73%]), fragile X testing was abnormal in 4 of 861 (0.46% [95% CI: 0.36%-0.56%]), and CMA identified deletions or duplications in 154 of 848 patients (18.2% [95% CI: 14.76%-21.64%]). CMA results for 59 of 848 patients (7.0% [95% CI: 5.5%-8.5%]) were considered abnormal, which includes variants associated with known genomic disorders or variants of possible significance. CMA results were normal in 10 of 852 patients (1.2%) with abnormal karyotype due to balanced rearrangements or unidentified marker chromosome. CMA with whole-genome coverage and CMA with targeted genomic regions detected clinically relevant copy-number changes in 7.3% (51 of 697) and 5.3% (8 of 151) of patients, respectively, both higher than karyotype. With the exception of recurrent deletion and duplication of chromosome 16p11.2 and 15q13.2q13.3, most copy-number changes were unique or identified in only a small subset of patients. CONCLUSIONS: CMA had the highest detection rate among clinically available genetic tests for patients with ASD. Interpretation of microarray data is complicated by the presence of both novel and recurrent copy-number variants of unknown significance. Despite these limitations, CMA should be considered as part of the initial diagnostic evaluation of patients with ASD. Pediatrics 2010; 125: e727-e735 C1 [Shen, Yiping; Dies, Kira A.; Holm, Ingrid A.; Bridgemohan, Carolyn; Sobeih, Magdi M.; Caronna, Elizabeth B.; Miller, Karen J.; Frazier, Jean A.; Silverstein, Iris; Picker, Jonathan; Weissman, Laura; Raffalli, Peter; Jeste, Shafali; Demmer, Laurie A.; Peters, Heather K.; Brewster, Stephanie J.; Kowalczyk, Sara J.; Rosen-Sheidley, Beth; McGowan, Caroline; Duda, Andrew W., III; Lincoln, Sharyn A.; Lowe, Kathryn R.; Schonwald, Alison; Robbins, Michael; Hisama, Fuki; Wolff, Robert; Becker, Ronald; Nasir, Ramzi; Urion, David K.; Milunsky, Jeff M.; Rappaport, Leonard; Gusella, James F.; Walsh, Christopher A.; Wu, Bai-Lin; Miller, David T.] Autism Consortium, Boston, MA USA. [Shen, Yiping; Wu, Bai-Lin; Miller, David T.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Holm, Ingrid A.; Peters, Heather K.; Brewster, Stephanie J.; Lowe, Kathryn R.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Holm, Ingrid A.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Milunsky, Jeff M.] Childrens Hosp, Dev Med Ctr, Boston, MA 02115 USA. [Sobeih, Magdi M.; Raffalli, Peter; Jeste, Shafali; Robbins, Michael; Wolff, Robert; Urion, David K.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Picker, Jonathan; McGowan, Caroline; Lincoln, Sharyn A.; Hisama, Fuki; Walsh, Christopher A.; Miller, David T.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Shen, Yiping; Dies, Kira A.; Holm, Ingrid A.; Bridgemohan, Carolyn; Sobeih, Magdi M.; Picker, Jonathan; Weissman, Laura; Raffalli, Peter; Jeste, Shafali; Schonwald, Alison; Robbins, Michael; Hisama, Fuki; Wolff, Robert; Becker, Ronald; Nasir, Ramzi; Urion, David K.; Rappaport, Leonard; Gusella, James F.; Walsh, Christopher A.; Wu, Bai-Lin; Miller, David T.] Harvard Univ, Sch Med, Boston, MA USA. [Shen, Yiping; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Holm, Ingrid A.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. [Miller, Karen J.; Demmer, Laurie A.; Rosen-Sheidley, Beth] Floating Hosp Children, Tufts Med Ctr, Boston, MA USA. [Frazier, Jean A.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Frazier, Jean A.] UMass Mem Med Ctr, Worcester, MA USA. [Silverstein, Iris; Duda, Andrew W., III] Massachusetts Gen Hosp, Children LADDERS Clin, Boston, MA 02114 USA. [Wu, Bai-Lin] Fudan Univ, Shanghai Med Coll, Childrens Hosp, Dept Pediat, Shanghai 200433, Peoples R China. [Wu, Bai-Lin] Fudan Univ, Shanghai Med Coll, Childrens Hosp, Dept Pathol, Shanghai 200433, Peoples R China. [Wu, Bai-Lin] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China. RP Wu, BL (reprint author), Childrens Hosp, Dept Lab Med, 300 Longwood Ave,Farley 7, Boston, MA 02115 USA. EM bai-lin.wu@childrens.harvard.edu OI Torres, Alcy/0000-0001-5798-9161 FU Autism Speaks [AS2042]; Howard Hughes Medical Institute NR 42 TC 149 Z9 153 U1 6 U2 22 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2010 VL 125 IS 4 BP E727 EP E735 DI 10.1542/peds.2009-1684 PG 9 WC Pediatrics SC Pediatrics GA 577QR UT WOS:000276239600038 PM 20231187 ER PT J AU Li, M Balamuthusamy, S Khan, AM Maderdrut, JL Simon, EE Batuman, V AF Li, Min Balamuthusamy, Saravanan Khan, Altaf M. Maderdrut, Jerome L. Simon, Eric E. Batuman, Vecihi TI Pituitary adenylate cyclase-activating polypeptide ameliorates cisplatin-induced acute kidney injury SO PEPTIDES LA English DT Article DE Apoptosis; Cancer chemotherapy; Inflammation; p53; Renoprotection ID ACUTE-RENAL-FAILURE; VASOACTIVE-INTESTINAL-PEPTIDE; TUBULE EPITHELIAL-CELLS; TUMOR-SUPPRESSOR P53; 4 SPLICE VARIANTS; INDUCED APOPTOSIS; EXTRACELLULAR-MATRIX; MULTIPLE-MYELOMA; IN-VIVO; CANCER CELLS AB Cisplatin nephrotoxicity involves DNA damage, proinflammatory responses and apoptosis/necrosis of renal proximal tubular epithelial cells. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to protect kidneys from ischemic injury and light chain-induced damage by modulating inflammation. Confluent monolayer of HK-2 human renal cells were exposed to 50 mu M cisplatin in the presence or absence of either PACAP38 or p53 siRNA. Mice injected with cisplatin were also treated with PACAP38 daily for 3 days. The damage to HK-2 cells caused by cisplatin involved the activation of p53, caspase-7, and poly (ADP-ribose) polymerase-1 (PARP-1). PACAP38 prevented the decrease in the apurinic/apyrimidinic endonuclease-1 by suppressing p53 activation and blocked the cleavage of caspase-7 and PARP-1 in cisplatin-exposed cells. PACAP also markedly inhibited cisplatin-induced apoptotic tubule cell death. Exposure to cisplatin significantly suppressed the expression of fibronectin and collagens I and IV, and altered the integrin repertoire of human renal tubule cells, while PACAP partially reversed the reduction of fibronectin, collagen IV, and the integrin subunits in cells exposed to cisplatin. Experiments with PACAP receptor antagonists and siRNA silencing of p53 showed that the renoprotection with PACAP was mediated by the PAC(1) receptor and through both p53-dependent and independent suppression of apoptosis. PACAP was renoprotective in vivo and prevented the rise in blood urea nitrogen and creatinine in mice treated with cisplatin. These results suggest that p53 plays a pivotal role in decreased integrin-mediated extracellular matrix component expression in cisplatin-induced tubule cell apoptosis, and reveal a novel aspect of PACAP-mediated renoprotection. (C) 2009 Elsevier Inc. All rights reserved. C1 [Li, Min; Balamuthusamy, Saravanan; Khan, Altaf M.; Simon, Eric E.; Batuman, Vecihi] Tulane Univ, Sch Med, Dept Med, Sect Nephrol & Hypertens, New Orleans, LA 70112 USA. [Maderdrut, Jerome L.] Tulane Univ, Sch Med, Dept Med, Peptide Res Lab, New Orleans, LA 70112 USA. [Simon, Eric E.; Batuman, Vecihi] US Dept Vet Affairs, SE Louisiana Vet Hlth Care Syst, New Orleans, LA 70161 USA. RP Li, M (reprint author), Tulane Univ, Sch Med, Dept Med, Sect Nephrol & Hypertens, 1430 Tulane Ave,SL-45, New Orleans, LA 70112 USA. EM minlee@tulane.edu OI Batuman, Vecihi/0000-0002-1800-9009 FU Louisiana Board of Regents [013RCEEP-07]; Rudolph Matas Memorial Fund; Louisiana Cancer Research Consortium; Dialysis Clinic, Inc.; Arimura Foundation FX This work was supported in part by grant 013RCEEP-07 from the Research Commercialization and Educational Enhancement Program of the Louisiana Board of Regents, the Rudolph Matas Memorial Fund, the Louisiana Cancer Research Consortium, the Dialysis Clinic, Inc., and the Arimura Foundation. NR 62 TC 14 Z9 14 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD APR PY 2010 VL 31 IS 4 BP 592 EP 602 DI 10.1016/j.peptides.2009.12.018 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 586FE UT WOS:000276887600011 PM 20034524 ER PT J AU Simms, LJ Yufik, T Gros, DF AF Simms, Leonard J. Yufik, Tom Gros, Daniel F. TI Incremental Validity of Positive and Negative Valence in Predicting Personality Disorder SO PERSONALITY DISORDERS-THEORY RESEARCH AND TREATMENT LA English DT Article DE Big Five model; Big Seven model; personality disorder; dimensional models AB The Big Seven model of personality includes five dimensions similar to the Big Five model as well as two evaluative dimensions Positive Valence (PV) and Negative Valence (NV)-which reflect extremely positive and negative person descriptors, respectively. Recent theory and research have suggested that PV and NV predict significant variance in personality disorder (PD) above that predicted by the Big Five, but firm conclusions have not been possible because previous studies have been limited to only single measures of PV, NV, and the Big Five traits. In the present study, we replicated and extended previous findings using three markers of all key constructs including PV, NV, and the Big Five in a diverse sample of 338 undergraduates. Results of hierarchical multiple regression analyses revealed that PV incrementally predicted Narcissistic and Histrionic PDs above the Big Five and that NV nonspecifically incremented the prediction of most PDs. Implications for dimensional models of personality pathology are discussed. C1 [Simms, Leonard J.; Yufik, Tom] SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. [Gros, Daniel F.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Charleston, SC USA. RP Simms, LJ (reprint author), SUNY Buffalo, Dept Psychol, Pk Hall 218, Buffalo, NY 14260 USA. EM ljsimms@buffalo.edu FU NIMH NIH HHS [1R01MH080086, R01 MH080086-01A2, R01 MH080086] NR 38 TC 6 Z9 6 U1 0 U2 1 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1949-2715 J9 PERSONAL DISORD JI Personal. Disord. PD APR PY 2010 VL 1 IS 2 BP 77 EP 86 DI 10.1037/a0019752 PG 10 WC Psychology, Clinical SC Psychology GA V27OH UT WOS:000208622000001 PM 20730038 ER PT J AU Yang, JB Chen, ACH Wu, QH Jiang, S Liu, XM Xiong, LY Xia, YM AF Yang, Jiabin Chen, Aaron C-H. Wu, Qiuhe Jiang, Shan Liu, Xiaoming Xiong, Layuan Xia, Yumin TI The influence of temperature on 5-aminolevulinic acid-based photodynamic reaction in keratinocytes in vitro SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE 5-aminolaevulinic acid; cytokines; keratinocytes; photodynamic therapy; temperature ID DELTA-AMINOLEVULINIC-ACID; NORMAL MOUSE SKIN; PROTOPORPHYRIN-IX; HACAT CELLS; THERAPY; APOPTOSIS; ACCUMULATION; HYPERTHERMIA; PENETRATION; MECHANISMS AB Background/purpose Based on the observation that increasing skin temperature could improve 5-aminolevulinic acid (ALA) penetration and accumulation of protoporphyrin IX (PpIX) in the ALA-based photodynamic therapy (PDT), this study was designed to investigate how temperature change varied the therapeutic effect of ALA-based PDT in vitro. Methods HaCat cells were cultured with or without ALA at various temperatures. ALA uptake and PpIX accumulation were analyzed before laser irradiation as the baseline. After irradiation, cell death and cytokine secretions in the media, including interleukin (IL)-1 alpha, tumor necrosis factor (TNF)-alpha and basic fibroblast growth factor (bFGF) were assayed, and the morphological changes were recorded. Results With increasing temperature, the amount of ALA uptake, intracellular PpIX concentration and cell death increased in both the PDT and the non-PDT groups. Secretions of IL-1 alpha, TNF-alpha and bFGF also increased and reached a peak around 44-47 degrees C and then declined at a higher temperature. This biphasic response might be due to protein thermolysis that occurs when cells reach beyond thermal tolerance. Conclusions Elevating temperature could augment photodynamic reactions to a certain extent, but adverse effects occurred when cells were overheated. C1 [Jiang, Shan; Liu, Xiaoming; Xiong, Layuan; Xia, Yumin] Wuhan Univ, Dept Dermatol, Renmin Hosp, Wuhan 430060, Peoples R China. [Yang, Jiabin] Yangtze Univ, Dept Dermatol, Affiliated Hosp 1, Jinzhou, Peoples R China. [Chen, Aaron C-H.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Chen, Aaron C-H.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Wu, Qiuhe] Shandong Univ, Dept Plast & Burn Surg, Jinan Cent Hosp, Clin Coll, Jinan 250100, Peoples R China. RP Xia, YM (reprint author), Wuhan Univ, Dept Dermatol, Renmin Hosp, 238 Jiefang Rd, Wuhan 430060, Peoples R China. EM ymxia@whu.edu.cn NR 29 TC 11 Z9 11 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-4383 EI 1600-0781 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD APR PY 2010 VL 26 IS 2 BP 83 EP 88 PG 6 WC Dermatology SC Dermatology GA 570BS UT WOS:000275647200005 PM 20415739 ER PT J AU Liao, EC Driscoll, DN Donelan, MB AF Liao, Eric C. Driscoll, Daniel N. Donelan, Matthias B. TI Restoration of Brow Position and Contour with Tissue-Expanded Antegrade Foreheadplasty SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID PEDIATRIC BURN PATIENT; RECONSTRUCTION; COMPLICATIONS; EXPANSION; FLAP C1 [Liao, Eric C.; Driscoll, Daniel N.; Donelan, Matthias B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children, Boston, MA 02114 USA. RP Donelan, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM mdonelan@partners.org NR 17 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR PY 2010 VL 125 IS 4 BP 1263 EP 1267 DI 10.1097/PRS.0b013e3181d0ac41 PG 5 WC Surgery SC Surgery GA 583AQ UT WOS:000276644000030 PM 20335879 ER PT J AU Zelezniak, A Pers, TH Soares, S Patti, ME Patil, KR AF Zelezniak, Aleksej Pers, Tune H. Soares, Simao Patti, Mary Elizabeth Patil, Kiran Raosaheb TI Metabolic Network Topology Reveals Transcriptional Regulatory Signatures of Type 2 Diabetes SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID INDUCED INSULIN-RESISTANCE; LIFE-SPAN EXTENSION; SACCHAROMYCES-CEREVISIAE; SKELETAL-MUSCLE; CALORIE RESTRICTION; GENE-EXPRESSION; MITOCHONDRIAL DYSFUNCTION; LIPID-METABOLISM; NUCLEAR CONTROL; CHOLINE KINASE AB Type 2 diabetes mellitus (T2DM) is a disorder characterized by both insulin resistance and impaired insulin secretion. Recent transcriptomics studies related to T2DM have revealed changes in expression of a large number of metabolic genes in a variety of tissues. Identification of the molecular mechanisms underlying these transcriptional changes and their impact on the cellular metabolic phenotype is a challenging task due to the complexity of transcriptional regulation and the highly interconnected nature of the metabolic network. In this study we integrate skeletal muscle gene expression datasets with human metabolic network reconstructions to identify key metabolic regulatory features of T2DM. These features include reporter metabolites-metabolites with significant collective transcriptional response in the associated enzyme-coding genes, and transcription factors with significant enrichment of binding sites in the promoter regions of these genes. In addition to metabolites from TCA cycle, oxidative phosphorylation, and lipid metabolism (known to be associated with T2DM), we identified several reporter metabolites representing novel biomarker candidates. For example, the highly connected metabolites NAD+/NADH and ATP/ADP were also identified as reporter metabolites that are potentially contributing to the widespread gene expression changes observed in T2DM. An algorithm based on the analysis of the promoter regions of the genes associated with reporter metabolites revealed a transcription factor regulatory network connecting several parts of metabolism. The identified transcription factors include members of the CREB, NRF1 and PPAR family, among others, and represent regulatory targets for further experimental analysis. Overall, our results provide a holistic picture of key metabolic and regulatory nodes potentially involved in the pathogenesis of T2DM. C1 [Zelezniak, Aleksej; Soares, Simao; Patil, Kiran Raosaheb] Tech Univ Denmark, Ctr Microbial Biotechnol, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Pers, Tune H.] Tech Univ Denmark, Ctr Biol Sequence Anal, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Pers, Tune H.] Copenhagen Univ Hosp, Inst Prevent Med, Ctr Hlth & Soc, Copenhagen, Denmark. [Soares, Simao] Univ Minho, IBB Inst Biotechnol & Bioengn, Ctr Biol Engn, Braga, Portugal. [Patti, Mary Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Zelezniak, A (reprint author), Tech Univ Denmark, Ctr Microbial Biotechnol, Dept Syst Biol, DK-2800 Lyngby, Denmark. EM krp@bio.dtu.dk RI Patil, Kiran /B-9709-2009 OI Patil, Kiran /0000-0002-6166-8640 FU NIH [DK062948, DK060837]; NOVO scholarship; Graetz Fund FX MEP appreciates grant support from NIH grants DK062948 and DK060837 and the Graetz Fund. AZ acknowledges support from NOVO scholarship program 2008-9. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 41 Z9 41 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2010 VL 6 IS 4 AR e1000729 DI 10.1371/journal.pcbi.1000729 PG 13 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 602GA UT WOS:000278125300006 PM 20369014 ER PT J AU Sox, HC Helfand, M Grimshaw, J Dickersin, K Tovey, D Knottnerus, JA Tugwell, P AF Sox, Harold C. Helfand, Mark Grimshaw, Jeremy Dickersin, Kay Tovey, David Knottnerus, J. Andre Tugwell, Peter TI Comparative Effectiveness Research: Challenges for Medical Journals SO PLOS MEDICINE LA English DT Editorial Material C1 [Sox, Harold C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dartmouth Inst, Hanover, NH 03756 USA. [Helfand, Mark] Portland VA Med Ctr, Portland, OR USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Grimshaw, Jeremy] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Dickersin, Kay] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Tovey, David] Cochrane Lib, London, England. [Knottnerus, J. Andre] Univ Maastricht, Dept Gen Practice, Maastricht, Netherlands. [Tugwell, Peter] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Tugwell, Peter] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Sox, HC (reprint author), Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dartmouth Inst, Hanover, NH 03756 USA. EM helfand@ohsu.edu RI Marusic, Ana/E-7683-2013; Knottnerus, Johannes/A-3829-2009 OI Peiperl, Laurence/0000-0003-1237-4846; Tugwell, Peter/0000-0001-5062-0556; Marusic, Ana/0000-0001-6272-0917; NR 7 TC 14 Z9 14 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD APR PY 2010 VL 7 IS 4 AR e1000269 DI 10.1371/journal.pmed.1000269 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 590PO UT WOS:000277239500001 PM 20436963 ER PT J AU Spilman, P Podlutskaya, N Hart, MJ Debnath, J Gorostiza, O Bredesen, D Richardson, A Strong, R Galvan, V AF Spilman, Patricia Podlutskaya, Natalia Hart, Matthew J. Debnath, Jayanta Gorostiza, Olivia Bredesen, Dale Richardson, Arlan Strong, Randy Galvan, Veronica TI Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-beta Levels in a Mouse Model of Alzheimer's Disease SO PLOS ONE LA English DT Article ID PROTEIN TRANSGENIC MICE; LIFE-SPAN; MAMMALIAN PROTEIN; PLAQUE-FORMATION; ALPHA-SYNUCLEIN; AUTOPHAGY; PATHWAY; YEAST; TOR; INDUCTION AB Background: Reduced TOR signaling has been shown to significantly increase lifespan in a variety of organisms [1,2,3,4]. It was recently demonstrated that long-term treatment with rapamycin, an inhibitor of the mTOR pathway[5], or ablation of the mTOR target p70S6K[6] extends lifespan in mice, possibly by delaying aging. Whether inhibition of the mTOR pathway would delay or prevent age-associated disease such as AD remained to be determined. Methodology/Principal Findings: We used rapamycin administration and behavioral tools in a mouse model of AD as well as standard biochemical and immunohistochemical measures in brain tissue to provide answers for this question. Here we show that long-term inhibition of mTOR by rapamycin prevented AD-like cognitive deficits and lowered levels of A beta(42), a major toxic species in AD[7], in the PDAPP transgenic mouse model. These data indicate that inhibition of the mTOR pathway can reduce A beta(42) levels in vivo and block or delay AD in mice. As expected from the inhibition of mTOR, autophagy was increased in neurons of rapamycin-treated transgenic, but not in non-transgenic, PDAPP mice, suggesting that the reduction in A beta and the improvement in cognitive function are due in part to increased autophagy, possibly as a response to high levels of A beta. Conclusions/Significance: Our data suggest that inhibition of mTOR by rapamycin, an intervention that extends lifespan in mice, can slow or block AD progression in a transgenic mouse model of the disease. Rapamycin, already used in clinical settings, may be a potentially effective therapeutic agent for the treatment of AD. C1 [Spilman, Patricia; Gorostiza, Olivia; Bredesen, Dale] Buck Inst Age Res, Novato, CA USA. [Podlutskaya, Natalia; Galvan, Veronica] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Podlutskaya, Natalia; Richardson, Arlan; Strong, Randy; Galvan, Veronica] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Richardson, Arlan; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Hart, Matthew J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Richardson, Arlan; Strong, Randy] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. [Richardson, Arlan; Strong, Randy] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. [Debnath, Jayanta] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. RP Spilman, P (reprint author), Buck Inst Age Res, Novato, CA USA. EM galvanv@uthscsa.edu FU Alzheimer's Association [NIRG-DDC-120433]; NIA Interventions Testing Center [U01AG022307]; San Antonio Nathan Shock Aging Center [P30AG-13319]; Research and Development Service of the Department of Veterans Affairs FX This work was supported by NIRG-DDC-120433 from the Alzheimer's Association to V. G. and by the NIA Interventions Testing Center (U01AG022307) to R. S. The authors also recognize the support of the San Antonio Nathan Shock Aging Center (P30AG-13319, A.R.) and the VA Neurodegeneration Research Center (REAP) from the Research and Development Service of the Department of Veterans Affairs (A.R., R.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 337 Z9 359 U1 8 U2 61 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 1 PY 2010 VL 5 IS 3 AR e9979 DI 10.1371/journal.pone.0009979 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 580AG UT WOS:000276418200050 PM 20376313 ER PT J AU Chintakuntlawar, AV Zhou, XH Rajaiya, J Chodosh, J AF Chintakuntlawar, Ashish V. Zhou, Xiaohong Rajaiya, Jaya Chodosh, James TI Viral Capsid Is a Pathogen-Associated Molecular Pattern in Adenovirus Keratitis SO PLOS PATHOGENS LA English DT Article ID INNATE IMMUNE-RESPONSE; TOLL-LIKE RECEPTOR-9; HUMAN CORNEAL FIBROBLASTS; GENE-TRANSFER; INTERLEUKIN-8 EXPRESSION; IMMUNOCOMPROMISED HOST; INFLAMMATORY RESPONSE; DENDRITIC CELLS; IN-VIVO; DNA AB Human adenovirus (HAdV) infection of the human eye, in particular serotypes 8, 19 and 37, induces the formation of corneal subepithelial leukocytic infiltrates. Using a unique mouse model of adenovirus keratitis, we studied the role of various virus-associated molecular patterns in subsequent innate immune responses of resident corneal cells to HAdV-37 infection. We found that neither viral DNA, viral gene expression, or viral replication was necessary for the development of keratitis. In contrast, empty viral capsid induced keratitis and a chemokine profile similar to intact virus. Transfected viral DNA did not induce leukocyte infiltration despite CCL2 expression similar to levels in virus infected corneas. Mice without toll-like receptor 9 (Tlr9) signaling developed clinical keratitis upon HAdV-37 infection similar to wild type mice, although the absolute numbers of activated monocytes in the cornea were less in Tlr9(-/-) mice. Virus induced leukocytic infiltrates and chemokine expression in mouse cornea could be blocked by treatment with a peptide containing arginine glycine aspartic acid (RGD). These results demonstrate that adenovirus infection of the cornea induces chemokine expression and subsequent infiltration by leukocytes principally through RGD contact between viral capsid and the host cell, possibly through direct interaction between the viral capsid penton base and host cell integrins. C1 [Chintakuntlawar, Ashish V.; Chodosh, James] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA. [Chintakuntlawar, Ashish V.; Zhou, Xiaohong; Rajaiya, Jaya; Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med,Howe Lab, Boston, MA USA. RP Chintakuntlawar, AV (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA. EM james_chodosh@meei.harvard.edu FU U.S. Public Health Service [R01 EY013124, P30 EY014104]; Massachusetts Lions Eye Research Fund, Inc; New England Corneal Transplant Research Fund; Falk Medical Research Fund; Research to Prevent Blindness FX Supported by U.S. Public Health Service grants R01 EY013124 and P30 EY014104, the Massachusetts Lions Eye Research Fund, Inc. (http://www.masslionseyeresearch. org/), the New England Corneal Transplant Research Fund, the Falk Medical Research Fund, and a Research to Prevent Blindness Unrestricted Grant to the Department of Ophthalmology, Harvard Medical School (http://www.rpbusa.org/rpb/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 25 Z9 25 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2010 VL 6 IS 4 AR e1000841 DI 10.1371/journal.ppat.1000841 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 596YS UT WOS:000277722400013 PM 20419141 ER PT J AU Maguen, S Cohen, G Cohen, BE Lawhon, GD Marmar, CR Seal, KH AF Maguen, Shira Cohen, Greg Cohen, Beth E. Lawhon, G. Dawn Marmar, Charles R. Seal, Karen H. TI The Role of Psychologists in the Care of Iraq and Afghanistan Veterans in Primary Care Settings SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE integrated care; veterans; mental health; post-traumatic stress disorder; health care ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH-SERVICES; STEPPED COLLABORATIVE CARE; TRAUMATIC BRAIN-INJURY; AFFAIRS PRIMARY-CARE; UNITED-STATES; DEPRESSION; OUTCOMES; MANAGEMENT AB Although military personnel serving in Iraq and Afghanistan are at high risk of developing mental health problems, many report significant barriers to care and few seek help. Integrated primary care is a comprehensive model of health care that aims to improve access to care and provides a framework to assess and meet the complex psychiatric needs of newly returning veterans by embedding mental health specialists within primary care. We describe the role of psychologists in a Department of Veterans Affairs (VA) integrated primary care clinic that serves veterans of Iraq and Afghanistan. Psychologists based in primary care can assist veterans with reintegration to civilian life by providing rapid mental health assessment, normalizing readjustment concerns, planning for veterans safety, implementing brief interventions within primary care. facilitating transition to additional mental health care, and informing veterans of other available psychosocial services. A case example demonstrating the psychologist's role highlights the benefits of an integrated care model. Implications of employing this model include reduction of symptoms and impairment by reducing stigma and barriers to seeking mental health care, increased motivation to engage ill treatment, and implementation of early interventions. This model may also be beneficial in the civilian health care sector with groups that are at high risk for mental health problems, yet experience barriers to care. particularly stigma. C1 [Maguen, Shira; Cohen, Greg; Cohen, Beth E.; Lawhon, G. Dawn; Marmar, Charles R.; Seal, Karen H.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Marmar, Charles R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St 116-P, San Francisco, CA 94121 USA. EM shira.maguen@va.gov NR 37 TC 9 Z9 9 U1 4 U2 11 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD APR PY 2010 VL 41 IS 2 BP 135 EP 142 DI 10.1037/a0018835 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 586EY UT WOS:000276886800007 ER PT J AU Xu, XE Qiao, M Zhang, Y Jiang, YH Wei, P Yao, J Gu, B Wang, YQ Lu, J Wang, ZG Tang, ZQ Sun, YH Wu, WS Shi, Q AF Xu, Xiaoen Qiao, Meng Zhang, Yang Jiang, Yinghua Wei, Ping Yao, Jun Gu, Bo Wang, Yaqi Lu, Jing Wang, Zhigang Tang, Zhaoqing Sun, Yihong Wu, Wenshu Shi, Qian TI Quantitative proteomics study of breast cancer cell lines isolated from a single patient: Discovery of TIMM17A as a marker for breast cancer SO PROTEOMICS LA English DT Article DE Biomarker; Biomedicine; Breast cancer; Mass spectra; Molecular profiling; Target for drugs ID VITAMIN-E ANALOGS; AMINO-ACIDS; CULTURE SILAC; TUMOR PROGRESSION; ADJUVANT THERAPY; PROTEINS; MITOCHONDRIA; EXPRESSION; BIOMARKERS; CARCINOMA AB The proteins involved in breast cancer initiation and progression are still largely elusive. To gain insights into these processes, we conducted quantitative proteomic analyses with 21T series of breast cell lines, which include a normal, primary tumor and a metastatic tumor that were isolated from a single patient. Stable isotope labeling of amino acid in cell culture followed by LC-MS/MS analysis was performed and deregulated proteins were identified using statistical analysis. Gene ontology analysis revealed that proteins involved in metabolic processes were the most deregulated in both tumorigenesis and metastasis. Interaction network analysis indicated that ERBB2 signaling played a critical role in tumorigenesis. In addition to known markers such as ERBB2 and E-cadherin, novel markers, including BRP44L, MTHFD2 and TIMM17A, were found to be overexpressed in 21T breast cancer cells and verified in additional breast cell lines. mRNA expression analysis as well as immunohistochemistry analysis in breast cancer tissues indicated that expression level of TIMM17A was directly correlated with tumor progression, and survival analysis suggested that TIMM17A was a powerful prognosis factor in breast cancer. More interestingly, overexpression and siRNA knockdown experiments indicated an oncogenic activity of TIMM17A in breast cancer. Our study provides a list of potential novel markers for breast cancer tumorigenesis and metastasis using a unique cell model. Further studies on TIMM17A as well as other markers on the list may reveal mechanisms that result in more effective therapeutics for cancer treatment. C1 [Xu, Xiaoen; Zhang, Yang; Jiang, Yinghua; Wei, Ping; Yao, Jun; Gu, Bo; Wang, Yaqi; Lu, Jing; Shi, Qian] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China. [Xu, Xiaoen; Zhang, Yang; Jiang, Yinghua; Wei, Ping; Yao, Jun; Gu, Bo; Wang, Yaqi; Lu, Jing; Shi, Qian] Fudan Univ, Coll Life Sci, Canc Hosp, Inst Canc, Shanghai 200032, Peoples R China. [Qiao, Meng; Wang, Zhigang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Qiao, Meng; Wang, Zhigang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Tang, Zhaoqing; Sun, Yihong] Fudan Univ, Zhongshan Hosp, Dept Gen Surg, Shanghai 200032, Peoples R China. [Wu, Wenshu] Maine Med Ctr Res Inst, Ctr Mol Med, Scarborough, ME USA. RP Shi, Q (reprint author), Fudan Univ, Inst Biomed Sci, 138 Yixueyuan Rd,Box 281, Shanghai 200032, Peoples R China. EM shiqian@fudan.edu.cn RI Wu, Wen-Shu/I-1258-2014 OI Wu, Wen-Shu/0000-0002-0225-2522 FU Pu Jiang Project [07pj14011]; Shu Guang Project [05SG05]; Science and Technology Commission [07dz 19505]; NSFC fund [30970653]; State Key Research Project [2008ZX10002-017, 2009ZX09301-011] FX The authors thank Dr. Arthur Pardee and Dr. Debajit Biswas (Dana Farber Cancer Institute) for their comments and suggestions on the manuscript. This work was supported by Pu Jiang Project (07pj14011), Shu Guang Project (05SG05), Science and Technology Commission of Shanghai Municipality Grant (07dz 19505), NSFC fund (30970653), State Key Research Project (2008ZX10002-017, 2009ZX09301-011) to Q. S. NR 46 TC 41 Z9 41 U1 1 U2 17 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD APR PY 2010 VL 10 IS 7 BP 1374 EP 1390 DI 10.1002/pmic.200900380 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 590UH UT WOS:000277253200004 PM 20198662 ER PT J AU Lemke, SP Schaefer, JA AF Lemke, Sonne P. Schaefer, Jeanne A. TI Recent Changes in the Prevalence of Psychiatric Disorders Among VA Nursing Home Residents SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PRIMARY-CARE CLINICS; MENTAL-ILLNESS; UNITED-STATES; SERVICE USE; HEALTH; VETERANS; TRENDS; AGE; EPIDEMIOLOGY AB Objective: This study identified recent changes in the prevalence of psychiatric disorders among Department of Veterans Affairs (VA) nursing home residents. Methods: Psychiatric diagnoses in administrative data-bases were summarized for nursing home residents in 1998, 2002, and 2006. Census prevalence rates were compared with findings from earlier VA nursing home surveys. Prevalence rates were compared for age groups and birth cohorts of VA nursing home admissions in 1998 (N=27,734) and 2006 (N=32,543). Results: Among residents in the census samples, prevalence rates for dementia and schizophrenia fluctuated moderately from 1990 to 2006, depression prevalence increased sharply, alcohol use disorder prevalence declined, and drug use disorder prevalence increased. Among 1998 and 2006 admissions, dementia prevalence increased for most birth cohorts but declined for most age groups (35% to 32% overall). Depression prevalence increased for all age groups and birth cohorts (27% to 37% overall), as did posttraumatic stress disorder prevalence (5% to 12% overall). Serious mental illness prevalence increased among the oldest residents and birth cohorts (19% to 22% overall). Alcohol use disorder prevalence declined for all birth cohorts and most age groups (18% to 16% overall), but drug use disorder prevalence increased substantially for younger age groups (6% to 9% overall). Conclusions: Examining differences in prevalence between birth cohorts and age groups can clarify trends in nursing home resident characteristics and improve projections of their future needs. (Psychiatric Services 61: 356-363, 2010) C1 [Lemke, Sonne P.; Schaefer, Jeanne A.] Ctr Hlth Care Evaluat, Palo Alto Hlth Care Syst, US Dept Vet Affairs, Menlo Pk, CA 94025 USA. RP Lemke, SP (reprint author), Ctr Hlth Care Evaluat, Palo Alto Hlth Care Syst, US Dept Vet Affairs, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM sonne.lemke@va.gov FU Department of Veterans Affairs [IIR 03-243]; Veterans Health Administration; Office of Research and Development Health Services Research and Development Service (HSRD) FX This research was supported in part by grant IIR 03-243 from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Health Services Research and Development Service (HSR&D). The findings and conclusions are those of the authors and do not necessarily represent those of the Department of Veterans Affairs or HSR&D. The authors thank Kathy Fung, M. S., and Kirsten Unger-Hu, M. S., for their valuable contributions to data management and analyses. NR 24 TC 8 Z9 8 U1 0 U2 2 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 APR PY 2010 VL 61 IS 4 BP 356 EP 363 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 577WH UT WOS:000276254200006 PM 20360274 ER PT J AU Harris, AHS Kivlahan, DR Bowe, T Humphreys, KN AF Harris, Alex H. S. Kivlahan, Daniel R. Bowe, Thomas Humphreys, Keith N. TI Pharmacotherapy of Alcohol Use Disorders in the Veterans Health Administration SO PSYCHIATRIC SERVICES LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; ADDICTION TREATMENT CENTERS; SUBSTANCE-USE DISORDERS; TREAT ALCOHOLISM; NALTREXONE; DEPENDENCE; ADOPTION; MEDICATIONS; PREVALENCE; TRIALS AB Objective: Acamprosate, oral and long-acting injectable naltrexone, and disulfiram are approved for treatment of alcohol dependence. Their availability and consideration of their use in treatment are now standards of high-quality care. This study determined rates of medication initiation among Veterans Health Administration (VHA) patients. Methods: VHA pharmacy and administrative data were used to identify patients with alcohol use disorder diagnoses in fiscal years (FY) 2006 and 2007 and the proportion (nationally and by facility) who received each medication. Patient characteristics associated with receipt were also examined. Results: Among more than a quarter-million patients with alcohol use disorder diagnoses, the percentage receiving any of the medications increased from 2.8% in FY 2006 to 3.0% in FY 2007. Receipt of these medications was more likely among patients who received specialty addiction care, those with alcohol dependence (compared with abuse), those younger than 55 years, and females. In the patient subgroups examined, the largest proportion to receive any of the medications was 11.6%. Across 128 VHA facilities, rates of use among patients in the sample who had received past-year specialty addiction treatment ranged from 0% to 20.5%; rates ranged from 0% to 4.3% among those with no specialty treatment. Patient preferences and medical contraindications could not be determined from the data. Conclusions: Findings suggest the need to better understand systemwide variation in use of these medications and their use as a rough proxy for availability and consideration of pharmacotherapy-a standard of care with strong organizational support. (Psychiatric Services 61:392-398, 2010) C1 [Harris, Alex H. S.; Bowe, Thomas; Humphreys, Keith N.] US Dept Vet Affairs, VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Harris, Alex H. S.; Bowe, Thomas; Humphreys, Keith N.] Stanford Univ, Sch Med, Menlo Pk, CA USA. [Kivlahan, Daniel R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Kivlahan, Daniel R.] Univ Washington, Sch Med, Seattle, WA USA. RP Harris, AHS (reprint author), US Dept Vet Affairs, VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd,MC152, Menlo Pk, CA 94025 USA. EM alexander.harris2@va.gov FU VA Office of Research and Development, Health Services Research and Development Service [MRP-05-168-1] FX This study was funded in part by grant MRP-05-168-1 from the VA Office of Research and Development, Health Services Research and Development Service. The authors thank David Oslin, M. D., for his helpful comments and suggestions. The views expressed herein are not necessarily those of the Department of Veteran Affairs. NR 32 TC 35 Z9 35 U1 3 U2 4 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 APR PY 2010 VL 61 IS 4 BP 392 EP 398 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 577WH UT WOS:000276254200011 PM 20360279 ER PT J AU Hunt, J Eisenberg, D Kilbourne, AM AF Hunt, Justin Eisenberg, Daniel Kilbourne, Amy M. TI Consequences of Receipt of a Psychiatric Diagnosis for Completion of College SO PSYCHIATRIC SERVICES LA English DT Article ID EDUCATIONAL-ATTAINMENT; ALCOHOL-CONSUMPTION; BIPOLAR-I; PSYCHOSOCIAL DISABILITY; UNIVERSITY-STUDENTS; MENTAL-HEALTH; DISORDERS; DEPRESSION; POPULATION; PREVALENCE AB Objective: The purpose of this study was to evaluate the independent associations between DSM-IV psychiatric disorders and the failure to complete college among college entrants. Methods: Data were from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The sample included 15,800 adults, aged 22 years and older, who at least entered college. Diagnoses were made with the NESARC survey instrument, the Alcohol Use Disorder and Associated Disability Interview Schedule-DSM-IV Version. The large sample permitted analysis of multiple psychiatric disorders in the same multivariable logistic regression models. Given the frequent comorbidity of these disorders, this approach is an important step toward disentangling the independent roles of disorders in postsecondary educational outcomes. Results: Evaluation of the independent associations between specific psychiatric disorders and postsecondary educational attainment showed that five diagnoses were positively and significantly associated with the failure to graduate from college. Four were axis I diagnoses: bipolar I disorder, marijuana use disorder, amphetamine use disorder, and cocaine use disorder. One was an axis II diagnosis: antisocial personality disorder. Conclusions: This study provides new data on DSM-IV diagnoses associated with the failure to complete postsecondary education. The findings suggest that psychiatric factors play a significant role in college academic performance, and the benefits of prevention, detection, and treatment of psychiatric illness may therefore include higher college graduation rates. (Psychiatric Services 61:399-404, 2010) C1 [Hunt, Justin] Univ Arkansas Med Sci, Dept Psychiat & Behav Sci, Little Rock, AR 72205 USA. [Eisenberg, Daniel] Univ Michigan, Sch Publ Hlth, Dept Hlth Policy & Management, Ann Arbor, MI 48109 USA. [Kilbourne, Amy M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. [Kilbourne, Amy M.] US Dept Vet Affairs, Hlth Serv Res & Dev, Serious Mental Illness Treatment Res & Evaluat Ct, Ann Arbor, MI USA. RP Hunt, J (reprint author), Univ Arkansas Med Sci, Dept Psychiat & Behav Sci, 4301 W Markham St,755, Little Rock, AR 72205 USA. EM huntjustinb@uams.edu FU Robert Wood Johnson Foundation FX The Robert Wood Johnson Foundation provided salary support (two-year research fellowship for Dr. Hunt) through its Clinical Scholars Program. NR 44 TC 23 Z9 23 U1 2 U2 11 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 APR PY 2010 VL 61 IS 4 BP 399 EP 404 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 577WH UT WOS:000276254200012 PM 20360280 ER PT J AU Salzer, MS Palmer, SC Kaplan, K Brusilovskiy, E Ten Have, T Hampshire, M Metz, J Coyne, JC AF Salzer, Mark S. Palmer, Steven C. Kaplan, Katy Brusilovskiy, Eugene Ten Have, Thomas Hampshire, Maggie Metz, James Coyne, James C. TI A randomized, controlled study of Internet peer-to-peer interactions among women newly diagnosed with breast cancer SO PSYCHO-ONCOLOGY LA English DT Article DE Internet; peer support; breast cancer; well-being ID SUPPORT GROUPS; INSIGHTFUL DISCLOSURE; INSTRUMENT; THERAPY; IMPACT AB Objective: Peer-to-peer interactions are associated with enhanced psychosocial adjustment among women with breast cancer. Millions of women with cancer and others with various health conditions use the Internet to establish peer relationships, usually without professional moderation. This paper reports findings from the first randomized, controlled study of the benefits of these types of Internet-based peer interactions. Methods: This pilot study involved seventy-eight women who were recently diagnosed with breast cancer. Participants were randomly assigned to either an Internet peer support condition or Internet-based educational control condition. Data were gathered at baseline and 4- and 12-months. Primary outcomes of interest were psychological distress and quality of life. Results: Contrary to hypotheses, participants in the Internet peer support condition tended to do worse over time on primary outcome measures. There were no differences between groups on secondary outcomes of perceived social support, self-efficacy, or hope. Paradoxically, many women in the Internet peer support condition actively participated and reported high levels of satisfaction, suggesting some self-perceived benefits. Conclusions: These results suggest that Internet based peer-to-peer interactions may not necessarily be universally beneficial despite the positive experiences reported by many participants. Further research is needed to understand the magnitude of this effect with a larger sample. Moreover, these results raise questions about the need to understand the comparative effectiveness of Internet-based communications by group structure (i.e., unstructured/structured; unmoderated/moderated) and the effect of content (i.e., expression of fear/anxiety, insightful disclosures, etc.) on outcomes. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Salzer, Mark S.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Salzer, Mark S.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Salzer, MS (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,3rd Floor CMHPSR, Philadelphia, PA 19104 USA. EM Mark.Solzer@uphs.upenn.edu FU National Cancer Institute [1R21CA098888-01A1] FX The study was supported by a study funded by the National Cancer Institute (Salzer, P. I.: 1R21CA098888-01A1). NR 20 TC 43 Z9 43 U1 1 U2 11 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD APR PY 2010 VL 19 IS 4 BP 441 EP 446 DI 10.1002/pon.1586 PG 6 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 585CF UT WOS:000276801200013 PM 19484712 ER PT J AU Ott, MJ AF Ott, Mary Jane TI The Art and Science of Mindfulness: Integrating Mindfulness into Psychology and the Helping Professions SO PSYCHO-ONCOLOGY LA English DT Book Review C1 [Ott, Mary Jane] Dana Farber Canc Inst, Nursing Serv, Boston, MA 02115 USA. [Ott, Mary Jane] Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. RP Ott, MJ (reprint author), Dana Farber Canc Inst, Nursing Serv, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD APR PY 2010 VL 19 IS 4 BP 447 EP 448 DI 10.1002/pon.1688 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 585CF UT WOS:000276801200014 ER PT J AU Nock, MK Park, JM Finn, CT Deliberto, TL Dour, HJ Banaji, MR AF Nock, Matthew K. Park, Jennifer M. Finn, Christine T. Deliberto, Tara L. Dour, Halina J. Banaji, Mahzarin R. TI Measuring the Suicidal Mind: Implicit Cognition Predicts Suicidal Behavior SO PSYCHOLOGICAL SCIENCE LA English DT Article DE suicide; suicide attempt; prediction; IAT ID SELF-INJURIOUS THOUGHTS; ASSOCIATION TEST; VALIDITY; SAMPLE; RISK; METAANALYSIS; DEPRESSION; GENE AB Suicide is difficult to predict and prevent because people who consider killing themselves often are unwilling or unable to report their intentions. Advances in the measurement of implicit cognition provide an opportunity to test whether automatic associations of self with death can provide a behavioral marker for suicide risk. We measured implicit associations about death/suicide in 157 people seeking treatment at a psychiatric emergency department. Results confirmed that people who have attempted suicide hold a significantly stronger implicit association between death/suicide and self than do psychiatrically distressed individuals who have not attempted suicide. Moreover, the implicit association of death/suicide with self was associated with an approximately 6-fold increase in the odds of making a suicide attempt in the next 6 months, exceeding the predictive validity of known risk factors (e. g., depression, suicide-attempt history) and both patients' and clinicians' predictions. These results provide the first evidence of a behavioral marker for suicidal behavior and suggest that measures of implicit cognition may be useful for detecting and predicting sensitive clinical behaviors that are unlikely to be reported. C1 [Nock, Matthew K.; Deliberto, Tara L.; Dour, Halina J.; Banaji, Mahzarin R.] Harvard Univ, Dept Psychol, Boston, MA 02115 USA. [Park, Jennifer M.; Finn, Christine T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Nock, MK (reprint author), William James Hall,33 Kirkland St 1280, Cambridge, MA 02138 USA. EM nock@wjh.harvard.edu FU NIMH NIH HHS [R03 MH076047, MH076047] NR 30 TC 126 Z9 128 U1 2 U2 34 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD APR PY 2010 VL 21 IS 4 BP 511 EP 517 DI 10.1177/0956797610364762 PG 7 WC Psychology, Multidisciplinary SC Psychology GA 585XG UT WOS:000276863100009 PM 20424092 ER PT J AU Barrett, LF Kensinger, EA AF Barrett, Lisa Feldman Kensinger, Elizabeth A. TI Context Is Routinely Encoded During Emotion Perception SO PSYCHOLOGICAL SCIENCE LA English DT Article DE emotion; perception; context ID FACIAL EXPRESSIONS; LANGUAGE; FACE; CATEGORIZATION; RECOGNITION; BRAIN AB In the present study, we investigated whether context is routinely encoded during emotion perception. For the first time, we show that people remember the context more often when asked to label an emotion in a facial expression than when asked to judge the expression's simple affective significance (which can be done on the basis of the structural features of the face alone). Our findings are consistent with an emerging literature showing that facial muscle actions (i.e., structural features of the face), when viewed in isolation, might be insufficient for perceiving emotion. C1 [Barrett, Lisa Feldman] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Program, Cambridge, MA 02138 USA. [Barrett, Lisa Feldman; Kensinger, Elizabeth A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Barrett, LF (reprint author), Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. EM barretli@bc.edu FU NIH HHS [DP1 OD003312, DP1 OD003312-03, DP1OD003312]; NIMH NIH HHS [MH080833, R01 MH080833] NR 32 TC 78 Z9 84 U1 4 U2 24 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0956-7976 EI 1467-9280 J9 PSYCHOL SCI JI Psychol. Sci. PD APR PY 2010 VL 21 IS 4 BP 595 EP 599 DI 10.1177/0956797610363547 PG 5 WC Psychology, Multidisciplinary SC Psychology GA 585XG UT WOS:000276863100024 PM 20424107 ER PT J AU Li, XB Ricci, R Large, CH Anderson, B Nahas, Z Bohning, DE George, MS AF Li, Xingbao Ricci, Raffaella Large, Charles H. Anderson, Berry Nahas, Ziad Bohning, Daryl E. George, Mark S. TI Interleaved transcranial magnetic stimulation and fMRI suggests that lamotrigine and valproic acid have different effects on corticolimbic activity SO PSYCHOPHARMACOLOGY LA English DT Article DE Transcranial magnetic stimulation; Neuroimaging; Motor cortex; Corticolimbic system; Lamotrigine; Valproic acid; fMRI; Anticonvulsant ID ANTERIOR CINGULATE CORTEX; CORTICAL EXCITABILITY; ANTIEPILEPTIC DRUGS; BIPOLAR DISORDER; MOTOR CORTEX; FUNCTIONAL CONNECTIVITY; BOLD-FMRI; TMS; MECHANISMS; MOOD AB Combined transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) can be used to study anticonvulsant drugs. A previous study showed that lamotrigine (LTG) inhibited brain activation induced when TMS was applied over motor cortex, whereas it increased activation induced by TMS applied over prefrontal cortex. The present double-blind, placebo-controlled, crossover study in 30 healthy subjects again combined TMS and fMRI to test whether the effects seen previously with LTG would be confirmed and to compare these with a second anticonvulsant drug, valproic acid (VPA). Statistical parametric mapping analysis showed that both LTG and VPA, compared to placebo, inhibited TMS-induced activation of the motor cortex. In contrast, when TMS was applied over prefrontal cortex, LTG increased the activation of limbic regions, confirming previous results; VPA had no effect. We conclude that LTG and VPA have similar inhibitory effects on motor circuits, but differing effects on the prefrontal corticolimbic system. The study demonstrates that a combination of TMS and fMRI techniques may be useful in the study of the effects of neuroactive drugs on specific brain circuits. C1 [Li, Xingbao; Ricci, Raffaella; Anderson, Berry; Nahas, Ziad; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. [Li, Xingbao; Bohning, Daryl E.; George, Mark S.] Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. [Large, Charles H.] GlaxoSmithKline SpA, Med Res Ctr, Verona, Italy. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Li, XB (reprint author), Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, 502N,67 President St, Charleston, SC 29425 USA. EM lixi@musc.edu OI Ricci, Raffaella/0000-0003-3422-2552 FU GlaxoSmithKline; Center for Advanced Imaging Research and Brain Stimulation Laboratory infrastructure and resources FX This study was funded primarily by an unrestricted research grant from GlaxoSmithKline to Dr. George, as well as from Center for Advanced Imaging Research and Brain Stimulation Laboratory infrastructure and resources. CHL is a full-time employee of GlaxoSmithKline S. p. A. None of the other authors has equity or financial conflicts. Drs. Li and George had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 45 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 2010 VL 209 IS 3 BP 233 EP 244 DI 10.1007/s00213-010-1786-y PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 572AM UT WOS:000275798400003 PM 20195575 ER PT J AU Swan, JS Ying, J Stahl, J Kong, CY Moy, B Roy, J Halpern, E AF Swan, J. Shannon Ying, Jun Stahl, James Kong, Chung Yin Moy, Beverly Roy, Jessica Halpern, Elkan TI Initial development of the Temporary Utilities Index: a multiattribute system for classifying the functional health impact of diagnostic testing SO QUALITY OF LIFE RESEARCH LA English DT Article DE Utility theory; Quality of life; Cost-effectiveness; Decision theory; Screening ID QUALITY-OF-LIFE; COST-EFFECTIVENESS; PSYCHOLOGICAL IMPACT; BREAST-CANCER; COLONOSCOPY; PREFERENCE; DISEASE; BIOPSY; ACCEPTABILITY; ANGIOGRAPHY AB The effects of testing and screening on quality of life may influence the future behavior of society, but have not been quantified. We derived a health classification and survey items for the morbidities of testing and screening, to be the foundation of a multiattribute utility instrument, the Temporary Utilities Index. Seventy-six women ranked the importance of attributes of the testing process after breast biopsy. Seven survey items on the testing process were subsequently developed and assessed for clarity by a second group of 19 patients. The items cover attributes of mental and physical well-being before, during, and after testing. A survey panel of 164 subjects accessed online used the items to endorse expected and experienced effects of colon screening and mammography. They also endorsed items from a colorectal benefits and barriers scale, a risk perception scale, and EQ-5D, to utilize in the analyses of validity of the TUI items. Based on criteria from the literature and limited psychometric analysis, the items showed evidence of practicality, validity, and a strong association with barriers. The TUI health classification and survey items show evidence of validity, and may inform economic analysis, once combined with utility weights. C1 [Swan, J. Shannon; Stahl, James; Kong, Chung Yin; Halpern, Elkan] Harvard Univ, Inst Technol Assessment, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Swan, J. Shannon; Ying, Jun; Roy, Jessica] Indiana Univ, Dept Radiol, Indianapolis, IN 46202 USA. [Ying, Jun] Univ Cincinnati, Med Ctr, Cincinnati, OH 45229 USA. [Stahl, James; Moy, Beverly] Harvard Univ, Dept Internal Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Swan, JS (reprint author), Harvard Univ, Inst Technol Assessment, Massachusetts Gen Hosp, Sch Med, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM Shannon@mgh-ita.org NR 49 TC 6 Z9 6 U1 2 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD APR PY 2010 VL 19 IS 3 BP 401 EP 412 DI 10.1007/s11136-010-9587-7 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 567RO UT WOS:000275464500012 PM 20084464 ER PT J AU Kilbourne, AM Fullerton, C Dausey, D Pincus, HA Hermann, RC AF Kilbourne, A. M. Fullerton, C. Dausey, D. Pincus, H. A. Hermann, R. C. TI A framework for measuring quality and promoting accountability across silos: the case of mental disorders and co-occurring conditions SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID SUBSTANCE USE DISORDERS; HEALTH-CARE; OLDER PATIENTS; ADULTS; IMPROVEMENT; ILLNESSES; OUTCOMES; DISEASE; BURDEN; ABUSE AB Background Quality measures can be effective tools for improving delivery of care and patient outcomes. Co-occurring conditions (COCs), including general medical conditions and substance use disorders, are the rule rather than the exception in patients with serious mental health disorders and lead to substantial morbidity and mortality burden. COCs among persons with mental health disorders are often treated by separate systems ("silos") in the US healthcare system, making it difficult to establish expectations for performance, assign accountability for measure results and ultimately improve quality of care for this group. Objectives A framework for measuring quality of care for COCs is proposed by reviewing the current state of quality for COCs and examples of quality measures based on the Donabedian model. Methods and framework The framework will also be applied to better define which providers are accountable for quality improvement, to ultimately ensure that quality measures have an impact on improving care for COCs. C1 [Kilbourne, A. M.] VA Ann Arbor HSR&D Ctr Excellence, VA Ann Arbor Natl Serious Mental Illness Treatmen, Ann Arbor, MI USA. [Kilbourne, A. M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Fullerton, C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Fullerton, C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Dausey, D.] Carnegie Mellon Univ, Dept Publ Policy & Management, H John Heinz III Sch Publ Policy, Pittsburgh, PA 15213 USA. [Pincus, H. A.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Pincus, H. A.] New York Presbyterian Hosp, New York, NY USA. [Pincus, H. A.] Irving Inst Clin & Translat Res, New York, NY USA. [Hermann, R. C.] Tufts Univ New England Med Ctr, Inst Clin Res & Hlth Policy Studies, CQAIMH, Boston, MA USA. RP Kilbourne, AM (reprint author), VA Ann Arbor SMITREC 11H, 2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM amykilbo@umich.edu FU Veterans Health Administration, Health Services Research and Development Service [IIR 02-283, IIR 07-115]; Robert Wood Johnson Foundation Depression in Primary Care; Department of Veterans Affairs; Robert Wood Johnson Foundation Substance Abuse Policy Research; National Institute of Mental Health; National Center for Research Resources [UL1 RR024156]; Mental Heath Therapeutics CERT at Rutgers; State University of New Jersey; Agency for Healthcare Research and Quality (AHRQ) [5 U18 HS016097] FX This work was supported by the Veterans Health Administration, Health Services Research and Development Service (IIR 02-283, IIR 07-115; AMK, PI), the Robert Wood Johnson Foundation Depression in Primary Care National Program (HAP, director), the Department of Veterans Affairs, the Robert Wood Johnson Foundation Substance Abuse Policy Research Program (DD) and the National Institute of Mental Health (CF). This work was also completed with the support of the Robert Wood Johnson Foundation Depression in Primary Care; Linking Clinical and System Strategies Program, the Irving Institute for Clinical and Translational Awards Grant Number UL1 RR024156 from the National Center for Research Resources, and the Mental Heath Therapeutics CERT at Rutgers, the State University of New Jersey, funded by the Agency for Healthcare Research and Quality (AHRQ) (5 U18 HS016097). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 31 TC 15 Z9 15 U1 2 U2 8 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD APR PY 2010 VL 19 IS 2 BP 113 EP 116 DI 10.1136/qshc.2008.027706 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 575NG UT WOS:000276073300008 PM 20142404 ER PT J AU Pomerantz, SR Choy, G AF Pomerantz, Stuart R. Choy, Garry TI Net Assets: PowerPoint Pearls for Radiology Presentations. Part I SO RADIOLOGY LA English DT Editorial Material ID IMAGE-MANIPULATION COMMANDS C1 [Pomerantz, Stuart R.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Choy, Garry] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Pomerantz, SR (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, 55 Fruit St,Gray 2-B285, Boston, MA 02114 USA. EM netassets@rsna.org NR 7 TC 3 Z9 3 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2010 VL 255 IS 1 BP 19 EP 22 DI 10.1148/radiol.10092341 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 572VU UT WOS:000275863000006 PM 20308441 ER PT J AU Suit, H DeLaney, T Goldberg, S Paganetti, H Clasie, B Gerweck, L Niemierko, A Hall, E Flanz, J Hallman, J Trofimov, A AF Suit, Herman DeLaney, Thomas Goldberg, Saveli Paganetti, Harald Clasie, Ben Gerweck, Leo Niemierko, Andrzej Hall, Eric Flanz, Jacob Hallman, Josh Trofimov, Alexei TI Proton vs carbon ion beams in the definitive radiation treatment of cancer patients SO RADIOTHERAPY AND ONCOLOGY LA English DT Review DE Protons; Carbon ions; TCP; NTCP ID CELL LUNG-CANCER; RELATIVE BIOLOGICAL EFFECTIVENESS; LOCALIZED PROSTATE-CANCER; SALIVARY-GLAND TUMORS; RANDOMIZED CLINICAL-TRIAL; FAST-NEUTRON RADIOTHERAPY; LINEAR-QUADRATIC MODEL; SKULL-BASE; UVEAL MELANOMA; NECK-CANCER AB Background and purpose: Relative to X-ray beams, proton [H-1] and carbon ion [C-12] beams provide superior distributions due primarily to their finite range. The principal differences are LET, low for H-1 and high for C-12, and a narrower penumbra of C-12 beams. Were C-12 to yield a higher TCP for a defined NTCP than H-1 therapy, would LET, fractionation or penumbra width be the basis? Methods: Critical factors of physics, radiation biology of H-1 and C-12 ion beams, neutron therapy and selected reports of TCP and NTCP from H-1 and C-12 irradiation of nine tumor categories are reviewed. Results: Outcome results are based on low dose per fraction H-1 and high dose per fraction C-12 therapy. Assessment of the role of LET and dose distribution vs dose fractionation is not now feasible. Available data indicate that TCP increases with BED with H-1 and C-12 TCPs overlaps. Frequencies of GIII NTCPs were higher after H-1 than C-12 treatment. Conclusions: Assessment of the efficacy of H-1 vs C-12 therapy is not feasible, principally due to the dose fractionation differences. Further, there is no accepted policy for defining the CTV-GTV margin nor definition of TCP. Overlaps of H-1 and C-12 ion TCPs at defined BED ranges indicate that TCPs are determined in large measure by dose, BED. Late GIII NTCP was higher in H-1 than C-12 patients, indicating LET as a significant factor. We recommend trials of H-1 vs (1)2C with one variable, i.e. LET. The resultant TCP vs NTCP relationship will indicate which beam yields higher TCP for a specified NTCP at a defined dose fractionation. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 95 (2010) 3-22 C1 [Suit, Herman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Hall, Eric] Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA. RP Suit, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM hsuit@partners.org FU NCI [C06 CA059267]; DoE [DE-SC001634]; NASA [NNJ05H138G]; NIAD [U19A1067773]; [CO6-CA059267] FX The authors are very pleased to thank Peter Biggs, George Chen, Karen Doppke, Martijn Englesman, Tim Lehane, Hanne Kooy, Jung Kung and John Wolfgang for their assistance with provision of reference material and data analysis. Also thanks to Julie M. Finn for her important participation in preparation of this manuscript. These co-authors are proud to acknowledge the partial support of their work by these governmental grants: B. Claise, C06 CA059267; L. Gerweck, NCI Grant # C06 CA059267; E. Hall, DE-SC001634 [DoE], NNJ05H138G [NASA] and U19A1067773 [NIAD]; A. Trofimov CO6-CA059267. NR 136 TC 83 Z9 86 U1 2 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD APR PY 2010 VL 95 IS 1 BP 3 EP 22 DI 10.1016/j.radonc.2010.01.015 PG 20 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 598EM UT WOS:000277816000002 PM 20185186 ER PT J AU Paganetti, H Goitein, M Parodi, K AF Paganetti, Harald Goitein, Michael Parodi, Katia TI Spread-out antiproton beams deliver poor physical dose distributions for radiation therapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Antiprotons; Radiation therapy; Monte Carlo ID NUCLEON ANNIHILATION PROCESS; LOW-ENERGY; BIOLOGICAL EFFECTIVENESS; (P)OVER-BAR-P ANNIHILATION; BRANCHING RATIOS; REST; PROTONS; RADIOTHERAPY; CARBON; DEPTH AB Background and purpose: Antiprotons have been suggested as a possibly superior modality for radiotherapy, due to the energy released when they annihilate, which enhances the Bragg peak and introduces a high-LET component to the dose. Previous studies have focused on small-diameter near-monoenergetic antiproton beams. The goal of this work was to study more clinically relevant beams. Methods: We used Monte Carlo techniques to simulate 120 and 200 MeV beams of both antiprotons and protons of 1 x 1 and 10 x 10 cm(2) areas, impinging on water. Results: An annihilating antiproton loses little energy locally; most goes into long-range secondary particles. When clinically typical field sizes are considered, these particles create a substantial dose halo around the primary field and degrade its lateral fall-off. Spreading the dose in depth further intensifies these effects. Conclusions: The physical dose distributions of spread-out antiproton beams of clinically relevant size (e.g. 10 x 10 cm(2) area) are substantially inferior to those of proton beams, exhibiting a dose halo and broadened penumbra. Studies on the value of antiproton beams, taking radiobiological effectiveness into account, need to assess such realistic beams and determine whether their inferior dose distributions do not undermine the potential value of antiprotons for all but the smallest fields. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 95 (2010) 79-86 C1 [Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Paganetti, Harald; Goitein, Michael] Harvard Univ, Sch Med, Boston, MA USA. [Parodi, Katia] Heidelberg Ion Beam Therapy Ctr, Heidelberg, Germany. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. EM hpaganetti@partners.org NR 37 TC 10 Z9 10 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD APR PY 2010 VL 95 IS 1 BP 79 EP 86 DI 10.1016/j.radonc.2009.03.020 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 598EM UT WOS:000277816000011 PM 19394098 ER PT J AU Ramakrishna, N Rosca, F Friesen, S Tezcanli, E Zygmanszki, P Hacker, F AF Ramakrishna, Naren Rosca, Florin Friesen, Scott Tezcanli, Evrim Zygmanszki, Piotr Hacker, Fred TI A clinical comparison of patient setup and intra-fraction motion using frame-based radiosurgery versus a frameless image-guided radiosurgery system for intracranial lesions SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Frameless; Radiosurgery; Image-guided; Stereotactic ID BRAIN RADIATION-THERAPY; STEREOTACTIC RADIOSURGERY; TARGET LOCALIZATION; QUALITY-ASSURANCE; RADIOTHERAPY; ACCURACY; METASTASES; IMMOBILIZATION; VERIFICATION; EXPERIENCE AB Background and purpose: A comparison of patient positioning and intra-fraction motion using invasive frame-based radiosurgery with a frameless X-ray image-guided system utilizing a thermoplastic mask for immobilization. Materials and methods: Overall system accuracy was determined using 57 hidden-target tests. Positioning agreement between invasive frame-based setup and image-guided (IG) setup, and intra-fraction displacement, was evaluated for 102 frame-based SRS treatments. Pre and post-treatment imaging was also acquired for 7 patients (110 treatments) immobilized with an aquaplast mask receiving fractionated IG treatment. Results: The hidden-target tests demonstrated a mean error magnitude of 0.7 mm (SD = 0.3 mm). For SRS treatments, mean deviation between frame-based and image-guided initial positioning was 1.0 mm (SD = 0.5 mm). Fusion failures were observed among 3 patients resulting in aberrant predicted shifts. The image-guidance system detected frame slippage in one case. The mean intra-fraction shift magnitude observed for the BRW frame was 0.4 mm (SD = 0.3 mm) compared to 0.7 mm (SD = 0.5 mm) for the fractionated patients with the mask system. Conclusions: The overall system accuracy is similar to that reported for invasive frame-based SRS. The intra-fraction motion was larger with mask-immobilization, but remains within a range appropriate for stereotactic treatment. These results support clinical implementation of frameless radiosurgery using the Novalis Body Exac-Trac system. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 95 (2010) 109-115 C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ramakrishna, N (reprint author), MD Anderson Canc Ctr Orlando, Dept Radiat Oncol, 1400 S Orange Ave,MP 760, Orlando, FL 32806 USA. EM naren.ramakrishna@orhs.org OI Hacker, Fred/0000-0001-7535-7598 NR 27 TC 50 Z9 51 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD APR PY 2010 VL 95 IS 1 BP 109 EP 115 DI 10.1016/j.radonc.2009.12.030 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 598EM UT WOS:000277816000016 PM 20116123 ER PT J AU Batista, LM Lima, FO Januzzi, JL Donahue, V Snydeman, C Greer, DM AF Batista, Leonardo M. Lima, Fabricio O. Januzzi, James L., Jr. Donahue, Vivian Snydeman, Colleen Greer, David M. TI Feasibility and safety of combined percutaneous coronary intervention and therapeutic hypothermia following cardiac arrest SO RESUSCITATION LA English DT Article DE Hypothermia; Myocardial infarction; Resuscitation; Heart arrest; Catheterization ID ELEVATION MYOCARDIAL-INFARCTION; 2007 FOCUSED UPDATE; VENTRICULAR-FIBRILLATION; COMATOSE SURVIVORS; TASK-FORCE; ARRHYTHMIAS; ASYSTOLE; IMPROVE; INJURY AB Review: Mild therapeautic hypothermia (MTH) has been associated with cardiac dysrhythmias, coagulopathy and infection. After restoration of spontaneous circulation (ROSC), many cardiac arrest patients undergo percutaneous coronary intervention (PCI). The safety and feasibility of combined MTH and PCI remains unclear. This is the first study to evaluate whether PCI increases cardiac risk or compromises functional outcomes in comatose cardiac arrest patients who undergo MTH. Methods: Ninety patients within a 6-h window following cardiac arrest and ROSC were included. Twenty subjects (23%) who underwent PCI following MTH induction were compared to 70 control patients who underwent MTH without PCI. The primary endpoint was the rate of dysrhythmias; secondary endpoints were time-to-MTH induction, rates of adverse events (dysrhythmia, coagulopathy, hypotension and infection) and mortality. Results: Patients who underwent PCI plus MTH suffered no statistical increase in adverse events (P = .054). No significant difference was found in the rates of dysrhythmias (P = .27), infection (P = .90), coagulopathy (P = .90) or hypotension (P = .08). The PCI plus MTH group achieved similar neurological outcomes (modified Rankin Scale (mRS) <= 3 (P = .42) and survival rates (P = .40). PCI did not affect the speed of MTH induction; the target temperature was reached in both groups without a significant time difference (P = .29). Conclusion: Percutaneous coronary intervention seems to be feasible when combined with MTH, and is not associated with increased cardiac or neurological risk. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Batista, Leonardo M.; Lima, Fabricio O.; Greer, David M.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr,Med Sch, Boston, MA USA. [Januzzi, James L., Jr.; Donahue, Vivian; Snydeman, Colleen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang Ambulatory Care Ctr, Suite 720,55 Fruit St, Boston, MA 02114 USA. EM dgreer@partners.org RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 NR 23 TC 41 Z9 45 U1 3 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD APR PY 2010 VL 81 IS 4 BP 398 EP 403 DI 10.1016/j.resuscitation.2009.12.016 PG 6 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 583VE UT WOS:000276707200007 PM 20083333 ER PT J AU Giani, A Cigada, M Esmaili, DD Salvetti, P Luccarelli, S Marziani, E Luiselli, C Sabella, P Cereda, M Eandi, C Staurenghi, G AF Giani, Andrea Cigada, Mario Esmaili, Daniel D. Salvetti, Paola Luccarelli, Saverio Marziani, Ermengarda Luiselli, Cristiano Sabella, Pierfilippo Cereda, Matteo Eandi, Chiara Staurenghi, Giovanni TI ARTIFACTS IN AUTOMATIC RETINAL SEGMENTATION USING DIFFERENT OPTICAL COHERENCE TOMOGRAPHY INSTRUMENTS SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE artifacts; comparison; optical coherence tomography; retinal boundaries; retinal segmentation; spectral domain ID DIABETIC MACULAR EDEMA; THICKNESS; DIAGNOSIS; DISEASES AB Purpose: The purpose of this study was to compare and evaluate artifact errors in automatic inner and outer retinal boundary detection produced by different time-domain and spectral-domain optical coherence tomography (OCT) instruments. Methods: Normal and pathologic eyes were imaged by six different OCT devices. For each instrument, standard analysis protocols were used for macular thickness evaluation. Error frequencies, defined as the percentage of examinations affected by at least one error in retinal segmentation (EF-exam) and the percentage of total errors per total B-scans, were assessed for each instrument. In addition, inner versus outer retinal boundary delimitation and central (1,000 mu m) versus noncentral location of errors were studied. Results: The study population of the EF-exam for all instruments was 25.8%. The EF-exam of normal eyes was 6.9%, whereas in all pathologic eyes, it was 32.7% (P < 0.0001). The EF-exam was highest in eyes with macular holes, 83.3%, followed by epiretinal membrane with cystoid macular edema, 66.6%, and neovascular age-related macular degeneration, 50.3%. The different OCT instruments produced different EF-exam values (P < 0.0001). The Zeiss Stratus produced the highest percentage of total errors per total B-scans compared with the other OCT systems, and this was statistically significant for all devices (P <= 0.005) except the Optovue RTvue-100 (P = 0.165). Conclusion: Spectral-domain OCT instruments reduce, but do not eliminate, errors in retinal segmentation. Moreover, accurate segmentation is lower in pathologic eyes compared with normal eyes for all instruments. The important differences in EF among the instruments studied are probably attributable to analysis algorithms used to set retinal inner and outer boundaries. Manual adjustments of retinal segmentations could reduce errors, but it will be important to evaluate interoperator variability. RETINA 30: 607-616, 2010 C1 [Giani, Andrea] IRCCS, GB Bietti Eye Fdn, Rome, Italy. [Cigada, Mario; Salvetti, Paola; Luccarelli, Saverio; Marziani, Ermengarda; Luiselli, Cristiano; Sabella, Pierfilippo; Staurenghi, Giovanni] Univ Milan, Sacco Hosp, Dept Clin Sci Luigi Sacco, Eye Clin, Milan, Italy. [Esmaili, Daniel D.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA USA. [Cereda, Matteo] Sacro Cuore Hosp Negrar, Dept Ophthalmol, Verona, Italy. [Eandi, Chiara] Univ Turin, Dept Clin Physiopathol, Eye Clin, Turin, Italy. RP Giani, A (reprint author), Univ Milan Italy, Sacco Hosp, Eye Clin,Sch Ophthalmol 2, Dept Clin Sci Luigi Sacco, W Via GB Grassi 74, I-20100 Milan, Italy. EM andreagiani@gmail.com OI Eandi, Chiara Maria/0000-0003-3656-1689; Luccarelli, Saverio/0000-0003-0908-9067 NR 17 TC 27 Z9 27 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD APR PY 2010 VL 30 IS 4 BP 607 EP 616 DI 10.1097/IAE.0b013e3181c2e09d PG 10 WC Ophthalmology SC Ophthalmology GA 608AE UT WOS:000278548900010 PM 20094011 ER PT J AU Kay, J Wordsworth, P Doyle, MK Smolen, J Buchanan, J Matteson, EL Hsia, EC Landewe, R Zhou, YY Shreekant, P Rahman, MU AF Kay, Jonathan Wordsworth, Paul Doyle, Mittie K. Smolen, Josef Buchanan, Jacqueline Matteson, Eric L. Hsia, Elizabeth C. Landewe, Robert Zhou, Yiying Shreekant, Parasuraman Rahman, Mahboob U. CA GO-AFTER Investigators TI GOLIMUMAB SIGNIFICANTLY IMPROVES PHYSICAL FUNCTION AND FATIGUE IN RA PATIENTS PREVIOUSLY TREATED WITH ANTI-TNF AGENTS: RESULTS FROM THE GO-AFTER STUDY SO RHEUMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the British-Society-Rheumatology/Spring Meeting of British-Health-Professional-in-Rheumatology CY APR 21-23, 2010 CL Birmingham, ENGLAND SP British Soc Rheumatol, British Hlth Profess Rheumatol C1 [Kay, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wordsworth, Paul] Nuffield Orthopaed Ctr, Oxford OX3 7LD, England. [Doyle, Mittie K.; Hsia, Elizabeth C.; Rahman, Mahboob U.] Univ Penn, Sch Med, Centocor RandD Inc, Malvern, PA USA. [Smolen, Josef] Med Univ Vienna, Vienna, Austria. [Buchanan, Jacqueline; Shreekant, Parasuraman] Johnson & Johnson Pharmaceut Serv LLC, Malvern, PA USA. [Matteson, Eric L.] Mayo Clin, Rochester, MN USA. [Landewe, Robert] Univ Hosp Maastricht, Maastricht, Netherlands. [Zhou, Yiying; GO-AFTER Investigators] Centocor Res & Dev Inc, Malvern, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD APR PY 2010 VL 49 SU 1 BP I110 EP I110 PG 1 WC Rheumatology SC Rheumatology GA 575DT UT WOS:000276047500278 ER PT J AU Smolen, J Wordsworth, P Doyle, MK Kay, J Matteson, EL Landewe, R Hsia, E Zhou, YY Rahman, MU AF Smolen, Josef Wordsworth, Paul Doyle, Mittie K. Kay, Jonathon Matteson, Eric L. Landewe, Robert Hsia, Elizabeth Zhou, Yiying Rahman, Mahboob U. CA GO-AFTER Investigator TI GOLIMUMAB IS EFFICACIOUS IN ANTI-TNF EXPERIENCED PTS WITH ACTIVE RA REGARDLESS OF TYPE OF AGENT OR REASON FOR DISCONTINUATION OF PRIOR ANTI-TNF: GO-AFTER STUDY SO RHEUMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the British-Society-Rheumatology/Spring Meeting of British-Health-Professional-in-Rheumatology CY APR 21-23, 2010 CL Birmingham, ENGLAND SP British Soc Rheumatol, British Hlth Profess Rheumatol C1 [Smolen, Josef] Med Univ Vienna, Hietzing Hosp, Vienna, Austria. [Wordsworth, Paul] Nuffield Orthopaed Ctr, Oxford OX3 7LD, England. [Doyle, Mittie K.; Hsia, Elizabeth; Rahman, Mahboob U.] Univ Penn, Sch Med, Centocor RandD, Malvern, PA USA. [Kay, Jonathon] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Landewe, Robert] Univ Hosp Maastricht, Maastricht, Netherlands. [Matteson, Eric L.] Mayo Clin, Rochester, MN USA. [Zhou, Yiying; GO-AFTER Investigator] Centocor Res & Dev Inc, Malvern, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD APR PY 2010 VL 49 SU 1 BP I108 EP I108 PG 1 WC Rheumatology SC Rheumatology GA 575DT UT WOS:000276047500273 ER PT J AU Goff, DC AF Goff, Donald C. TI SEARCHING FOR COGNITIVE ENHANCERS IN SCHIZOPHRENIA: THE TURNS PROGRAM STRATEGY SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Goff, Donald C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 118 EP 118 DI 10.1016/j.schres.2010.02.051 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800049 ER PT J AU Seidman, LJ Whitfield-Gabrieli, S Thermenos, HW Rosso, I Makris, N Milanovic, S Goldstein, JM Gabrieli, JDE Faraone, SV Tsuang, MT AF Seidman, Larry J. Whitfield-Gabrieli, Susan Thermenos, Heidi W. Rosso, Isabelle Makris, Nikos Milanovic, Snezana Goldstein, Jill M. Gabrieli, John D. E. Faraone, Stephen V. Tsuang, Ming T. TI DEFAULT NETWORK AND MEDIAL PREFRONTAL CORTEX DYSFUNCTION IN SCHIZOPHRENIA AND IN FIRST DEGREE RELATIVES OF PERSONS WITH SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Seidman, Larry J.; Thermenos, Heidi W.; Milanovic, Snezana; Goldstein, Jill M.; Tsuang, Ming T.] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr,Dept Psychiat,Publ, Boston, MA 02115 USA. [Seidman, Larry J.; Thermenos, Heidi W.; Makris, Nikos; Milanovic, Snezana; Goldstein, Jill M.] Harvard Univ, Sch Med, MIT, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Seidman, Larry J.; Thermenos, Heidi W.; Makris, Nikos; Milanovic, Snezana; Goldstein, Jill M.] Massachusetts Gen Hosp, Charlestown, MA USA. [Seidman, Larry J.; Thermenos, Heidi W.; Milanovic, Snezana; Goldstein, Jill M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Whitfield-Gabrieli, Susan; Gabrieli, John D. E.] MIT, Harvard Mit Div Hlth Sci & Technol, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, Susan; Gabrieli, John D. E.] Poitras Ctr Affect Disorders Res Cambridge, Cambridge, MA USA. [Rosso, Isabelle] Harvard Univ, McLean Hosp, Sch Med, Neuroimaging Ctr,Dept Psychiat, Belmont, MA 02178 USA. [Makris, Nikos] MGH, Ctr Morphometr Anal, Charlestown, MA USA. [Goldstein, Jill M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Faraone, Stephen V.] SUNY Syracuse, Genet Res Program, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, La Jolla, CA 92093 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 170 EP 171 DI 10.1016/j.schres.2010.02.198 PG 2 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800200 ER PT J AU Seidman, LJ Giuliano, AJ Meyer, EC Addington, J Cadenhead, KS Cannon, TD McGlashan, TH Perkins, DO Tsuang, MT Walkers, EF Woods, SW Heinssen, R Cornblatt, BA AF Seidman, Larry J. Giuliano, Anthony J. Meyer, Eric C. Addington, Jean Cadenhead, Kristen S. Cannon, Tyrone D. McGlashan, Thomas H. Perkins, Diana O. Tsuang, Ming T. Walkers, Elaine F. Woods, Scott W. Heinssen, Robert Cornblatt, Barbara A. TI NEUROPSYCHOLOGY OF THE PRODROME TO PSYCHOSIS IN THE NAPLS CONSORTIUM: RELATIONSHIP TO FAMILY HISTORY AND CONVERSION TO PSYCHOSIS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Seidman, Larry J.; Giuliano, Anthony J.; Tsuang, Ming T.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02115 USA. [Meyer, Eric C.] Texas A&M Univ, Hlth Sci Ctr, Coll Med, Dept Psychiat & Behav Sci, Waco, TX USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Cadenhead, Kristen S.; Tsuang, Ming T.] UCSD, Dept Psychiat, San Diego, CA USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Walkers, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Heinssen, Robert] NIMH, Div Adult Translat Res, Schizophrenia Spectrum Res Program, Bethesda, MD 20892 USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [Walkers, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Seidman, Larry J.; Giuliano, Anthony J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 176 EP 176 DI 10.1016/j.schres.2010.02.210 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800212 ER EF