FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Stewart, SE Hu, YP Hezel, DM Proujansky, R Lamstein, A Walsh, C Ben-Joseph, EP Gironda, C Jenike, M Geller, DA Pauls, DL AF Stewart, S. Evelyn Hu, Yu-Pei Hezel, Dianne M. Proujansky, Rachel Lamstein, Abby Walsh, Casey Ben-Joseph, Elana Pearl Gironda, Christina Jenike, Michael Geller, Daniel A. Pauls, David L. TI Development and Psychometric Properties of the OCD Family Functioning (OFF) Scale SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE obsessive-compulsive disorder; family; accommodation; functioning; scale ID OBSESSIVE-COMPULSIVE DISORDER; ACCOMMODATION; CHILDREN; RELIABILITY; ADOLESCENTS; IMPAIRMENT; PREDICTORS; SYMPTOMS; GUILT; AGE AB Obsessive-compulsive disorder (OCD) influences not only patients but also family members. Although the construct of family accommodation has received attention in OCD literature, no measures of overall family functioning are currently available. The OCD Family Functioning (OFF) Scale was developed to explore the context, extent, and perspectives of functional impairment in families affected by OCD. It is a three-part, self-report measure capturing independent perspectives of patients and relatives. A total of 400 subjects were enrolled between 2008 and 2010 from specialized OCD clinics and OCD research studies. Psychometric properties of this scale were examined including internal consistency, test-retest reliability, convergent and divergent validity, and exploratory factor analyses. Both patient and relative versions of the OFF Scale demonstrated excellent internal consistency (Cronbach's alpha coefficient = 0.96). The test-retest reliability was also adequate (ICC = 0.80). Factor analyses determined that the OFF Scale comprises a family functioning impairment factor and four OCD symptom factors that were consistent with previously reported OCD symptom dimension studies. The OFF Scale demonstrated excellent convergent validity with the Family Accommodation Scale and the Work and Social Adjustment Scale. Information gathered regarding emotional impact and family role-specific impairment was novel and not captured by other examined scales. The OFF Scale is a reliable and valid instrument for the clinical and research assessment of family functioning in pediatric and adult OCD. This will facilitate the exploration of family functioning impairment as a potential risk factor, as a moderator and as a treatment outcome measure in OCD. C1 [Stewart, S. Evelyn] Univ British Columbia, OCD Res Program, Vancouver, BC V5Z 1M9, Canada. [Stewart, S. Evelyn] Harvard Univ, Sch Med, Vancouver, BC, Canada. [Hu, Yu-Pei; Lamstein, Abby; Gironda, Christina] Mclean Hosp, OCD Inst, Belmont, MA USA. [Hezel, Dianne M.; Proujansky, Rachel; Walsh, Casey; Ben-Joseph, Elana Pearl] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Jenike, Michael] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Jenike, Michael] McLean Hosp, OCD Inst, Belmont, MA 02178 USA. [Geller, Daniel A.; Pauls, David L.] Harvard Univ, Med School, Cambridge, MA 02138 USA. RP Stewart, SE (reprint author), BC Childrens Hosp, Child & Family Res Inst, 938 W28th Ave,Room A3-118, Vancouver, BC V5Z 4H4, Canada. EM sevelynstewart@gmail.com OI Stewart, S. Evelyn/0000-0002-0994-6383 FU NIMH NIH HHS [R01 MH079489, R01MH79489-4] NR 37 TC 12 Z9 12 U1 3 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD JUN PY 2011 VL 25 IS 3 BP 434 EP 443 DI 10.1037/a0023735 PG 10 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 776AS UT WOS:000291507500012 PM 21553962 ER PT J AU Rowe, LS Doss, BD Hsueh, AC Libet, J Mitchell, AE AF Rowe, Lorelei Simpson Doss, Brian D. Hsueh, Annie C. Libet, Julian Mitchell, Alexandra E. TI Coexisting Difficulties and Couple Therapy Outcomes: Psychopathology and Intimate Partner Violence SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE couple therapy; relationship satisfaction; psychopathology; intimate partner violence; marriage ID MARITAL SATISFACTION; QUALITY AB Couples presenting for treatment of relationship distress often experience additional problems, including individual psychopathology and intimate partner violence (IPV). Both issues are associated with current and future poor relationship functioning in nontreatment samples, but relatively little is understood about their association with initial presentation and outcomes in couple therapy. The current study examined these associations in a sample of 177 heterosexual couples who received therapy at two Veteran's Affairs clinics. Unlike most studies of couple therapy outcomes, couples were not excluded from treatment specifically because of high levels of psychopathology or IPV. Results of Actor Partner Interdependence Model (APIM) analyses revealed actor and partner effects of depression, actor effects of anxiety, and partner effects of IPV on initial relationship satisfaction, such that greater coexisting difficulties were associated with poorer initial satisfaction. However, improvement in relationship satisfaction over the course of therapy was not associated with psychopathology, and, contrary to hypothesis, was positively associated with men's IPV prior to treatment, even when initial level of satisfaction was controlled. The results suggest that coexisting symptoms of psychopathology or IPV may not necessarily interfere with therapy outcomes and, indeed, therapy may have positive effects for couples with these problems. C1 [Rowe, Lorelei Simpson; Mitchell, Alexandra E.] So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA. [Doss, Brian D.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Hsueh, Annie C.] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Libet, Julian] Ralph H Johnson VA Med Ctr, Psychol Serv, Charleston, SC USA. RP Rowe, LS (reprint author), So Methodist Univ, Dept Psychol, POB 750442, Dallas, TX 75275 USA. EM lsimpson@smu.edu NR 8 TC 4 Z9 4 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD JUN PY 2011 VL 25 IS 3 BP 455 EP 458 DI 10.1037/a0023696 PG 4 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 776AS UT WOS:000291507500015 PM 21534671 ER PT J AU Webb, ML Rosen, H Taghinia, A McCarty, ER Cerrato, F Upton, J Labow, BI AF Webb, Michelle L. Rosen, Heather Taghinia, Amir McCarty, Erika R. Cerrato, Felecia Upton, Joseph Labow, Brian I. TI Incidence of Fanconi Anemia in Children with Congenital Thumb Anomalies Referred for Diepoxybutane Testing SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Congenital; Fanconi anemia; radius; hypoplasia; thumb ID BONE-MARROW FAILURE; REGISTRY; DIAGNOSIS; CANCER; RISKS AB Purpose Fanconi anemia (FA) is a rare genetic disorder of DNA repair that with near uniformity leads to bone marrow failure and resulting morbidity and mortality. Approximately 50% of FA patients are born with anomalies of the thumb or thumb and radius, and it has been recommended that all patients born with thumb anomalies undergo testing. However, the risk of FA in this population is unknown. We determined the incidence of FA in children with congenital thumb anomalies referred for FA testing and characterized those who tested positive. Methods We queried our database for patients who presented with congenital thumb anomalies and who underwent diepoxybutane (DEB) testing for FA between 1999 and 2008 at Children's Hospital Boston and the Dana-Farber Cancer Institute. Results During this time period, 543 congenital thumb anomaly patients (235 with thumb hypoplasia) presented to our institution. A total of 81 patients with thumb abnormalities underwent DEB testing. Six patients (7% of those tested; 1% of the total; 3% of thumb hypoplasia patients) had a positive DEB test consistent with the diagnosis of FA; all had other non-upper-extremity anomalies associated with FA. Of 6 FA patients, 5 had bilateral involvement; all had some degree of thumb hypoplasia (3 also had radial dysplasia). Mean age at testing was 2.6 years (SD 4.3). Most of the patients tested had multiple physical anomalies (n = 66). The anomaly distribution was: thumb hypoplasia and radial dysplasia (n = 29), thumb hypoplasia (n = 26), radial polydactyly (n = 12), radial polydactyly and radial dysplasia (n = 1), and proximally placed thumb and radial dysplasia (n = 1). Twelve patients had other thumb anomalies. Conclusions Although the incidence of FA in patients with thumb anomalies may be low, patients with thumb hypoplasia and other physical findings associated with FA, specifically cafe au lait spots and short stature, appear to have an increased risk of FA. Because hand surgeons see these patients early in life, they have the opportunity to refer these patients for FA testing to initiate early education, family genetic counseling, and treatment if warranted. (J Hand Surg 2011;36A: 1052-1057. Copyright (C) 2011 by the American Society for Surgery of the Hand. All rights reserved.) Type of study/level of evidence Prognostic IV. C1 [Labow, Brian I.] Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Fanconi Anemia & Bone Marrow Failure Multidiscipl, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Labow, BI (reprint author), Childrens Hosp, Dept Plast & Oral Surg, 300 Longwood Ave,Enders 1, Boston, MA 02115 USA. EM brian.labow@childrens.harvard.edu NR 22 TC 7 Z9 7 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUN PY 2011 VL 36A IS 6 BP 1052 EP 1057 DI 10.1016/j.jhsa.2011.02.018 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 776XD UT WOS:000291572900016 PM 21514743 ER PT J AU Fusco, DN Chung, RT AF Fusco, Dahlene N. Chung, Raymond T. TI New protease inhibitors for HCV - Help is on the way SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID NUCLEOSIDE POLYMERASE R7128; HEPATITIS-C; INFECTION; TELAPREVIR; PHARMACOKINETICS; PEGINTERFERON; COMBINATION; RIBAVIRIN; INFORM-1; SAFETY C1 [Fusco, Dahlene N.; Chung, Raymond T.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, GI Unit, 55 Fruit St,Warren 1007, Boston, MA 02114 USA. EM rtchung@partners.org NR 20 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JUN PY 2011 VL 54 IS 6 BP 1087 EP 1089 DI 10.1016/j.jhep.2010.12.016 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 776GR UT WOS:000291523000002 PM 21232563 ER PT J AU Bieganski, RM Yarmush, ML AF Bieganski, Robert M. Yarmush, Martin L. TI Novel ligands that target the mitochondrial membrane protein mitoNEET SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article DE Mitoneet; Autodock; Docking; Fluorescence; Iron-sulfur; Thiazolidinedione ID AMYOTROPHIC-LATERAL-SCLEROSIS; PPAR-GAMMA; TRANSGENIC MICE; PIOGLITAZONE; DOCKING; THIAZOLIDINEDIONE; CELLS; SYSTEM; NEURODEGENERATION; STABILIZATION AB Ligands of the thiazolidinedione (TZD) class of compounds, pioglitazone (Actos (TM)) and rosiglitazone (Avandia (TM)) are currently approved for treatment of type 2 diabetes and are known to bind to the PPAR-gamma gamma nuclear receptor subtype. Recent evidence suggesting PPAR-gamma independent action of the TZDs led to the discovery of a novel integral outer mitochondrial membrane protein, mitoNEET. In spite of the several reported X-ray crystal structures of the unbound form cif mitoNEET, the location and nature of the mitoNEET ligand binding sites (LBS) remain unknown. In this study, a molecular blind docking (BD) method was used to discover potential mitoNEET LBS and novel ligands, utilizing the program AutoDock Vina (v 1.0.2). Validation of BD was performed on the PPAR-gamma receptor (PDB ID: 1ZGY) with the test compound rosiglitazone, demonstrating that the binding conformation of rosiglitazone determined by AutoDock Vina matches well with that of the cocrystallized ligand (root mean square deviation of the heavy atoms 1.45 angstrom). The locations and a general ligand binding interaction model for the LBS were determined, leading to the discovery of novel mitoNEET ligands. An in vitro fluorescence binding assay utilizing purified recombinant mitoNEET protein was used to determine the binding affinity of a predicted mitoNEET ligand, and the data obtained is in good agreement with AutoDock Vina results. The discovery of potential mitoNEET ligand binding sites and novel ligands, opens up the possibility for detailed structural studies of mitoNEET-ligand complexes, as well as rational design of novel ligands specifically targeted for mitoNEET. (C) 2011 Elsevier Inc. All rights reserved. C1 [Bieganski, Robert M.; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [Bieganski, Robert M.; Yarmush, Martin L.] Shriners Hosp Children, Dept Surg, Boston, MA 02114 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM rbieg2008@gmail.com FU National Institute Of Diabetes And Digestive And Kidney Diseases [R01DK059766] FX The project described was supported by Award Number R01DK059766 from the National Institute Of Diabetes And Digestive And Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute Of Diabetes And Digestive And Kidney Diseases or the National Institutes of Health. We wish to gratefully acknowledge Max R. Bieganski for creating graphical content and providing technical support, and Dr. Sandra Wiley, from the Department of Pharmacology at the University of California, San Diego, for providing purified recombinant mitoNEET protein samples, as well as Prof. JoAnne Stubbe, from the Departments of Biology and Chemistry at the Massachusetts Institute of Technology, for providing access to the QM-4-SE fluorimeter used in this study. NR 41 TC 18 Z9 19 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1093-3263 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD JUN PY 2011 VL 29 IS 7 BP 965 EP 973 DI 10.1016/j.jmgm.2011.04.001 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA 774VL UT WOS:000291414700009 PM 21531159 ER PT J AU Jackson, VA Back, AL AF Jackson, Vicki A. Back, Anthony L. TI Teaching Communication Skills Using Role-Play: An Experience-Based Guide for Educators SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PALLIATIVE CARE; FACULTY-DEVELOPMENT; BAD-NEWS; ONCOLOGISTS; PHYSICIANS; PROGRAM AB Teaching advanced communication skills requires educators who are not only excellent communicators themselves but have the ability to deconstruct the components of the interaction and develop a cognitive approach that can be used across a variety of learners, diverse content, and under different time constraints while helping the learner develop the skill of self-reflection in a 'safe' and effective learning environment. The use of role-play in small groups is an important method to help learners cultivate the skills required to engage in nuanced, often difficult conversations with seriously ill patients. To be effective, educators utilizing role-play must help learners set realistic goals and know when and how to provide feedback to the learners in a way that allows a deepening of skills and a promotion of self-awareness. The challenge is to do this in a manner that does not cause too much anxiety for the learner. In this article we outline an approach to teaching communication skills to advanced learners through the use of different types of role-play, feedback, and debriefing. C1 [Jackson, Vicki A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Palliat Care Unit, Boston, MA 02115 USA. [Back, Anthony L.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. RP Jackson, VA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Palliat Care Unit, Founders 600,55 Fruit St, Boston, MA 02115 USA. EM VJackson@partners.org FU NIH [R25 119019] FX Dr. Back was supported by NIH R25 119019. NR 22 TC 23 Z9 23 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2011 VL 14 IS 6 BP 775 EP 780 DI 10.1089/jpm.2010.0493 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 775CC UT WOS:000291433700019 PM 21651366 ER PT J AU Hopwood, CJ Malone, JC Ansell, EB Sanislow, CA Gill, CM McGlashan, TH Pinto, A Markowitz, JC Shea, MT Skodol, AE Gunderson, JG Zanarini, MC Morey, LC AF Hopwood, Christopher J. Malone, Johanna C. Ansell, Emily B. Sanislow, Charles A. Gill, Carlos M. McGlashan, Thomas H. Pinto, Anthony Markowitz, John C. Shea, M. Tracie Skodol, Andrew E. Gunderson, John G. Zanarini, Mary C. Morey, Leslie C. TI PERSONALITY ASSESSMENT IN DSM-5: EMPIRICAL SUPPORT FOR RATING SEVERITY, STYLE, AND TRAITS SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID 5-FACTOR MODEL; DISCRIMINANT VALIDITY; DIMENSIONAL MODELS; CLINICAL UTILITY; DISORDERS; IV; CLASSIFICATION; RELIABILITY; BORDERLINE; PSYCHOPATHOLOGY AB Despite a general consensus that dimensional models are superior to the categorical representations of personality disorders in DSM-IV, proposals for how to depict personality pathology dimensions vary substantially. One important question involves how to separate clinical severity from the style of expression through which personality pathology manifests. This study empirically distinguished stylistic elements of personality pathology symptoms from the overall severity of personality disorder in a large, longitudinally assessed clinical sample (N = 605). Data suggest that generalized severity is the most important single predictor of current and prospective dysfunction, but that stylistic elements also indicate specific areas of difficulty. Normative personality traits tend to relate to the general propensity for personality pathology, but not stylistic elements of personality disorders. Overall, findings support a three-stage diagnostic strategy involving a global rating of personality disorder severity, ratings of parsimonious and discriminant valid stylistic elements of personality disorder, and ratings of normative personality traits. C1 [Hopwood, Christopher J.] Michigan State Univ, E Lansing, MI 48824 USA. [Ansell, Emily B.; Gill, Carlos M.; McGlashan, Thomas H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ansell, Emily B.; Gill, Carlos M.; McGlashan, Thomas H.; Gunderson, John G.; Zanarini, Mary C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ansell, Emily B.; Gill, Carlos M.; McGlashan, Thomas H.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Pinto, Anthony; Markowitz, John C.; Skodol, Andrew E.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Pinto, Anthony] Columbia Coll Phys & Surg, New York, NY USA. [Markowitz, John C.] Cornell Univ, Ithaca, NY 14853 USA. [Shea, M. Tracie] Brown Univ, Warren Alpert Med Sch, Dept Vet Affairs, Providence, RI 02912 USA. [Shea, M. Tracie] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Gunderson, John G.; Zanarini, Mary C.] McLean Hosp, Belmont, MA USA. [Morey, Leslie C.] Texas A&M Univ, College Stn, TX 77843 USA. [Sanislow, Charles A.] Wesleyan Univ, Middletown, CT 06459 USA. RP Hopwood, CJ (reprint author), Michigan State Univ, 107A Psychol, E Lansing, MI 48824 USA. EM hopwood2@msu.edu RI Morey, Leslie/B-5617-2008; Pinto, Anthony/D-2718-2017 OI Morey, Leslie/0000-0001-7711-5568; Pinto, Anthony/0000-0002-6078-7242 NR 44 TC 81 Z9 82 U1 2 U2 15 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD JUN PY 2011 VL 25 IS 3 BP 305 EP 320 PG 16 WC Psychiatry SC Psychiatry GA 774FG UT WOS:000291369900003 PM 21699393 ER PT J AU Apfel, BA Otte, C Inslicht, SS McCaslin, SE Henn-Haase, C Metzler, TJ Makotkine, I Yehuda, R Neylan, TC Marmar, CR AF Apfel, Brigitte A. Otte, Christian Inslicht, Sabra S. McCaslin, Shannon E. Henn-Haase, Clare Metzler, Thomas J. Makotkine, Iouri Yehuda, Rachel Neylan, Thomas C. Marmar, Charles R. TI Pretraumatic prolonged elevation of salivary MHPG predicts peritraumatic distress and symptoms of post-traumatic stress disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Neuroendocrinology; Post-traumatic stress disorder; Stress test; Salivary MHPG; Prospective study; Police ID HEART-RATE; PSYCHOLOGICAL STRESS; PTSD SYMPTOMS; PSYCHOBIOLOGICAL RESPONSES; PSYCHOMETRIC PROPERTIES; EMERGENCY-DEPARTMENT; CHILDHOOD TRAUMA; MEMORY STORAGE; PLASMA-LEVELS; NOREPINEPHRINE AB Post-traumatic stress disorder (PTSD) is associated with elevated catecholamines and increased sympathetic arousal. However, it is unknown whether this condition is a pre-existing vulnerability factor for PTSD or an acquired result of either trauma exposure or the development of FTSD symptoms. We sought to examine if salivary 3-methoxy-4-hydroxy-phenylglycol (MHPG) in response to a laboratory stressor prior to critical incident exposure predicts the development of PTSD symptoms and if early childhood trauma influences this relationship. In a prospective cohort study, 349 urban police officers were assessed during academy training (baseline) and 243 were reassessed 12 months after the start of active duty (follow-up). At baseline, participants observed a video consisting of police critical incidents. Salivary MHPG was measured before and immediately after the challenge, and after 20 min recovery. At follow-up, peritraumatic distress and PTSD symptoms were assessed in relationship to the worst critical incident during the past year. Participants with childhood trauma showed a trend towards higher MHPG increase to the challenge. Higher MHPG levels after 20 min recovery were associated with both higher levels of peritraumatic distress and PTSD symptoms at follow-up. In a path analysis, elevated MHPG levels predicted higher peritraumatic distress which in turn predicted higher levels of PTSD symptoms while the direct effect of elevated MHPG levels on PTSD symptoms was no longer significant. Prolonged elevation of salivary MHPG in response to a laboratory stressor marks a predisposition to experience higher levels of peritraumatic distress and subsequently more PTSD symptoms following critical incident exposure. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Apfel, Brigitte A.; Inslicht, Sabra S.; McCaslin, Shannon E.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Apfel, Brigitte A.; Inslicht, Sabra S.; McCaslin, Shannon E.; Metzler, Thomas J.; Neylan, Thomas C.] Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. [Otte, Christian] Univ Hosp Hamburg Eppendorf, Dept Psychiat, Hamburg, Germany. [Makotkine, Iouri; Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Henn-Haase, Clare; Marmar, Charles R.] NYU, Dept Psychiat, New York, NY 10016 USA. RP Apfel, BA (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, 116D,4150 Clement St, San Francisco, CA 94121 USA. EM brigitte.apfel@ucsf.edu FU Glaxo Smith Kline; Actelion; NIMH [5R01-MH056350-10] FX Dr. Neylan has served on the Pfizer-Advisory Panel and received research support from Glaxo Smith Kline and Actelion. Dr. Marmar has served on the Pfizer-Advisory Panel. All other authors declare that they have no conflicts of interest.; Funding for this study was provided by NIMH Grant 5R01-MH056350-10; the NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 67 TC 9 Z9 9 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUN PY 2011 VL 45 IS 6 BP 735 EP 741 DI 10.1016/j.jpsychires.2010.11.016 PG 7 WC Psychiatry SC Psychiatry GA 776XH UT WOS:000291573400004 PM 21196013 ER PT J AU Goodman, M Hazlett, EA Avedon, JB Siever, DR Chu, KW New, AS AF Goodman, Marianne Hazlett, Erin A. Avedon, Jennifer B. Siever, Daniel R. Chu, King-Wai New, Antonia S. TI Anterior cingulate volume reduction in adolescents with borderline personality disorder and co-morbid major depression SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Borderline personality disorder; Adolescent; Structural neuroimaging; MRI; anterior cingulate; Major depression ID CORTEX; AGGRESSION; SYMPTOMS; OUTCOMES; MATTER; GRAY; MRI AB Borderline Personality Disorder (BPD) is a serious illness characterized by emotional dysregulation, impulsivity, and impaired interpersonal relationships. Prior work shows the anterior cingulate gyrus (ACG)-a region primarily involved in assessing the salience of emotional information and regulating emotional responses-is smaller in adults with BPD. We tested the hypothesis that, similar to adults, adolescents with BPD would have reduced Brodmann area (BA)-24 volume. Thirteen adolescent inpatients with co-morbid BPD and Major Depressive Disorder (MDD) and 13 matched healthy controls received 3T-MRI scans. Using a cytoarchitecturally-derived approach measuring gray and white matter volume, we observed a Group x Cingulate BA (25,24,31,23,29) x Matter (gray, white) type interaction indicating the BPD/MDD adolescents had smaller BA24 volume in gray but not white matter. Greater number of suicide attempts and BPD symptom severity measured by the Diagnostic Interview for BPD-revised (DIB-R) total score but not depressive symptoms measured by the Beck Depression Inventory (BDI) was associated with smaller BA24 volume. Our preliminary findings suggest that BPD-related abnormalities in BA24 volume may occur early in the developmental course of BPD with MDD. Future studies examining samples of MDD patients with and without BPD co-morbidity will be needed to clarify whether BA24 volume reductions are specific to BPD. Published by Elsevier Ltd. C1 [Goodman, Marianne; Hazlett, Erin A.; Avedon, Jennifer B.; New, Antonia S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Goodman, M (reprint author), James J Peters Dept Vet Adm Med Ctr, 130 W Kingsbridge Rd,Off 3B-20B, Bronx, NY 10468 USA. EM Marianne.goodman@va.gov FU VA; NIMH [R01MH073911]; National Center for Research Resources (NCRR) [M01-Patient Care RR-0071]; Mental Illness Research and ClinicalCenter; VISN 3 Veterans Heath Administration FX This work was supported by a VA Career Development grant to MG and NIMH grant R01MH073911 to EAH. Other support came from grant M01-Patient Care RR-0071 from the National Center for Research Resources (NCRR) and the Mental Illness Research and ClinicalCenter, VISN 3 Veterans Heath Administration. These funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 27 TC 31 Z9 31 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUN PY 2011 VL 45 IS 6 BP 803 EP 807 DI 10.1016/j.jpsychires.2010.11.011 PG 5 WC Psychiatry SC Psychiatry GA 776XH UT WOS:000291573400013 PM 21145068 ER PT J AU Farwell, WR D'Avolio, LW Scranton, RE Lawler, EV Gaziano, JM AF Farwell, Wildon R. D'Avolio, Leonard W. Scranton, Richard E. Lawler, Elizabeth V. Gaziano, J. Michael TI Statins and Prostate Cancer Diagnosis and Grade in a Veterans Population SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CHOLESTEROL-LOWERING DRUGS; RISK; ASSOCIATION; COHORT; HEALTH; CAVEOLIN-1; TRIAL; CELLS AB Background Although prostate cancer is commonly diagnosed, few risk factors for high-grade prostate cancer are known and few prevention strategies exist. Statins have been proposed as a possible treatment to prevent prostate cancer. Methods Using electronic and administrative files from the Veterans Affairs New England Healthcare System, we identified 55 875 men taking either a statin or antihypertensive medication. We used age-and multivariable-adjusted Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer incidence among patients taking statins (n = 41 078) compared with patients taking antihypertensive medications (n = 14 797). We performed similar analyses for all lipid parameters including total cholesterol examining each lipid parameter as a continuous variable and by quartiles. All statistical tests were two-sided. Results Compared with men taking an antihypertensive medication, statin users were 31% less likely (HR = 0.69, 95% CI = 0.52 to 0.90) to be diagnosed with prostate cancer. Furthermore, statin users were 14% less likely (HR = 0.86, 95% CI = 0.62 to 1.20) to be diagnosed with low-grade prostate cancer and 60% less likely (HR = 0.40, 95% CI = 0.24 to 0.65) to be diagnosed with high-grade prostate cancer compared with antihypertensive medication users. Increased levels of total cholesterol were also associated with both total (HR = 1.02, 95% CI = 1.00 to 1.05) and high-grade (HR = 1.06, 95% CI = 1.02 to 1.10) prostate cancer incidence but not with low-grade prostate cancer incidence (HR = 1.01, 95% CI = 0.98 to 1.04). Conclusions Statin use is associated with statistically significantly reduced risk for total and high-grade prostate cancer, and increased levels of serum cholesterol are associated with higher risk for total and high-grade prostate cancer. These findings indicate that clinical trials of statins for prostate cancer prevention are warranted. C1 [Farwell, Wildon R.] VA Boston Healthcare Syst, Boston Div MAV 151, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. [Farwell, Wildon R.; Scranton, Richard E.; Lawler, Elizabeth V.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Lawler, Elizabeth V.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Farwell, WR (reprint author), VA Boston Healthcare Syst, Boston Div MAV 151, Massachusetts Vet Epidemiol Res & Informat Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM wfarwell@partners.org FU Department of Defense [W81XWH-08-2-0168]; Department of Veterans Affairs Office of Research and Development [601, 96] FX Research award W81XWH-08-2-0168 from the Department of Defense and grants 601 and 96 from the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development. NR 24 TC 44 Z9 44 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN PY 2011 VL 103 IS 11 BP 885 EP 892 DI 10.1093/jnci/djr108 PG 8 WC Oncology SC Oncology GA 775VG UT WOS:000291490900010 PM 21498780 ER PT J AU Newgard, CD Nelson, MJ Kampp, M Saha, S Zive, D Schmidt, T Daya, M Jui, J Wittwer, L Warden, C Sahni, R Stevens, M Gorman, K Koenig, K Gubler, D Rosteck, P Lee, J Hedges, JR AF Newgard, Craig D. Nelson, Maria J. Kampp, Michael Saha, Somnath Zive, Dana Schmidt, Terri Daya, Mohamud Jui, Jonathan Wittwer, Lynn Warden, Craig Sahni, Ritu Stevens, Mark Gorman, Kyle Koenig, Karl Gubler, Dean Rosteck, Pontine Lee, Jan Hedges, Jerris R. TI Out-of-Hospital Decision Making and Factors Influencing the Regional Distribution of Injured Patients in a Trauma System SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 10th Annual Academic Emergency Medicine Consensus Conference/Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 13, 2009 CL New Orleans, LA SP Soc Acad Emergency Med DE Triage; Cognitive reasoning; Emergency medical services; Trauma ID EMERGENCY MEDICAL-SERVICES; PARAMEDIC JUDGMENT; PROBABILISTIC LINKAGE; NATIONAL EVALUATION; FIELD TRIAGE; MORTALITY; SEVERITY; THINKING; CARE AB Background: The decision-making processes used for out-of-hospital trauma triage and hospital selection in regionalized trauma systems remain poorly understood. The objective of this study was to assess the process of field triage decision making in an established trauma system. Methods: We used a mixed methods approach, including emergency medical services (EMS) records to quantify triage decisions and reasons for hospital selection in a population-based, injury cohort (2006-2008), plus a focused ethnography to understand EMS cognitive reasoning in making triage decisions. The study included 10 EMS agencies providing service to a four-county regional trauma system with three trauma centers and 13 nontrauma hospitals. For qualitative analyses, we conducted field observation and interviews with 35 EMS field providers and a round table discussion with 40 EMS management personnel to generate an empirical model of out-of-hospital decision making in trauma triage. Results: A total of 64,190 injured patients were evaluated by EMS, of whom 56,444 (88.0%) were transported to acute care hospitals and 9,637 (17.1% of transports) were field trauma activations. For nontrauma activations, patient/family preference and proximity accounted for 78% of destination decisions. EMS provider judgment was cited in 36% of field trauma activations and was the sole criterion in 23% of trauma patients. The empirical model demonstrated that trauma triage is driven primarily by EMS provider "gut feeling" (judgment) and relies heavily on provider experience, mechanism of injury, and early visual cues at the scene. Conclusions: Provider cognitive reasoning for field trauma triage is more heuristic than algorithmic and driven primarily by provider judgment, rather than specific triage criteria. C1 [Newgard, Craig D.; Nelson, Maria J.; Kampp, Michael; Zive, Dana; Schmidt, Terri; Daya, Mohamud; Jui, Jonathan; Warden, Craig; Sahni, Ritu] Oregon Hlth & Sci Univ, Dept Emergency Med, Ctr Policy & Res Emergency Med, Portland, OR 97239 USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Schmidt, Terri] Clackamas Cty Amer Med Response, Clackamas, OR USA. [Daya, Mohamud; Stevens, Mark] Tualatin Valley Fire & Rescue, Aloha, OR USA. [Jui, Jonathan] Multnomah Cty Emergency Med Serv, Multnomah Cty Hlth Dept, Portland, OR USA. [Wittwer, Lynn] Clark Cty Emergency Med Serv, Vancouver, WA USA. [Warden, Craig; Gorman, Kyle; Koenig, Karl] Clackamas Cty Fire Dist 1, Clackamas, OR USA. [Sahni, Ritu] EMS & Trauma Syst, Oregon Dept Human Serv, Publ Hlth Div, Portland, OR USA. [Gubler, Dean] Legacy Emanuel Trauma Program, Portland, OR USA. [Rosteck, Pontine] NW Amer Med Response, Portland, OR USA. [Lee, Jan] Metrowest Ambulance, Hillsboro, OR USA. [Hedges, Jerris R.] Univ Hawaii Manoa, Dept Med, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Newgard, CD (reprint author), Oregon Hlth & Sci Univ, Dept Emergency Med, Ctr Policy & Res Emergency Med, 3181 SW Sam Jackson Pk Rd,Mail Code CR-114, Portland, OR 97239 USA. EM newgardc@ohsu.edu FU NCRR NIH HHS [UL1 RR024140, UL1 RR024140-01]; NIMHD NIH HHS [U54 MD007584] NR 30 TC 22 Z9 22 U1 1 U2 6 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 JUN PY 2011 VL 70 IS 6 BP 1345 EP 1353 DI 10.1097/TA.0b013e3182191a1b PG 9 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 775QR UT WOS:000291478500013 PM 21817971 ER PT J AU Aranson, NJ Ergul, E Patel, VI LaMuraglia, GM Kwolek, CJ Cambria, RP Conrad, MF AF Aranson, Nathan J. Ergul, Emel Patel, Virendra I. LaMuraglia, Glenn M. Kwolek, Christopher J. Cambria, Richard P. Conrad, Mark F. TI Timing of TEVAR Does Not Influence Mortality After Hybrid Repair of Thoracoabdominal Aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 16-18, 2011 CL Chicago, IL SP Soc Vasc Surg C1 [Aranson, Nathan J.; Ergul, Emel; Patel, Virendra I.; LaMuraglia, Glenn M.; Kwolek, Christopher J.; Cambria, Richard P.; Conrad, Mark F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Aranson, Nathan/0000-0001-8833-4643 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2011 VL 53 SU S BP 12S EP 12S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 774TY UT WOS:000291410700020 ER PT J AU Blazick, E Haurani, MJ Patel, VI LaMuraglia, GM Kwolek, CJ Conrad, MF AF Blazick, Elizabeth Haurani, Mounir J. Patel, Virendra I. LaMuraglia, Glenn M. Kwolek, Christopher J. Conrad, Mark F. TI Results of an Aggressive Surveillance and Retrieval Protocol for Inferior Vena Cava (IVC) Filter Removal SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 16-18, 2011 CL Chicago, IL SP Soc Vasc Surg C1 [Blazick, Elizabeth; Haurani, Mounir J.; Patel, Virendra I.; LaMuraglia, Glenn M.; Kwolek, Christopher J.; Conrad, Mark F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2011 VL 53 SU S BP 13S EP 14S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 774TY UT WOS:000291410700022 ER PT J AU Lombardi, JV Nienaber, CA Cambria, R Chiesa, R Teebken, O Lee, A Mossop, P Bharadwaj, P AF Lombardi, Joseph V. Nienaber, Christoph A. Cambria, Richard Chiesa, Roberto Teebken, Omke Lee, Anthony Mossop, Peter Bharadwaj, Priya TI Endovascular Treatment of Complicated Type B Aortic Dissection Using a Composite Device Design: Initial Results of a Prospective Multicenter Clinical Trial (STABLE) SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 16-18, 2011 CL Chicago, IL SP Soc Vasc Surg C1 [Lombardi, Joseph V.] Cooper Univ Hosp, Camden, NJ USA. [Nienaber, Christoph A.] Univ Hosp Rostock, Rostock, Germany. [Cambria, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chiesa, Roberto] Hosp San Raffaele, I-20132 Milan, Italy. [Teebken, Omke] Hannover Med Sch, Hannover, Germany. [Lee, Anthony] Christine E Lynn Heart & Vasc Inst, Boca Raton, FL USA. [Mossop, Peter] St Vincents Hosp, Melbourne, Vic, Australia. [Bharadwaj, Priya] Inst Med, Bloomington, IN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2011 VL 53 SU S BP 25S EP 25S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 774TY UT WOS:000291410700046 ER PT J AU Danczyk, RC Mitchell, EL Kryger, SG Burk, C Singh, S Liem, TK Landry, GJ Edwards, JM Petersen, BD Moneta, GL AF Danczyk, Rachel C. Mitchell, Erica L. Kryger, Sharon G. Burk, Chad Singh, Sarguni Liem, Timothy K. Landry, Gregory J. Edwards, James M. Petersen, Bryan D. Moneta, Gregory L. TI Comparing Patency and Salvage Rates between Multiple Ipsilateral Iliac Artery Stents and Isolated Iliac Artery Stents: Beyond TASC II SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 16-18, 2011 CL Chicago, IL SP Soc Vasc Surg C1 [Danczyk, Rachel C.; Mitchell, Erica L.; Kryger, Sharon G.; Burk, Chad; Singh, Sarguni; Liem, Timothy K.; Landry, Gregory J.; Moneta, Gregory L.] Oregon Hlth & Sci Univ, Div Vasc Surg, Portland, OR 97201 USA. [Edwards, James M.] Portland VA Med Ctr, Portland, OR USA. [Petersen, Bryan D.] Oregon Hlth & Sci Univ, Dotter Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2011 VL 53 SU S BP 63S EP 63S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 774TY UT WOS:000291410700120 ER PT J AU Patel, VI Mukhopadhyay, S Ergul, E Aranson, NJ Conrad, MF Kwolek, CJ Cambria, RP AF Patel, Virendra I. Mukhopadhyay, Shankha Ergul, Emel Aranson, Nathan J. Conrad, Mark F. Kwolek, Christopher J. Cambria, Richard P. TI Surgery for Descending Thoracic Aneurysms: Impact of Hospital Type on Operative Techniques and Outcomes in the US Medicare Population SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 16-18, 2011 CL Chicago, IL SP Soc Vasc Surg C1 [Patel, Virendra I.; Mukhopadhyay, Shankha; Ergul, Emel; Aranson, Nathan J.; Conrad, Mark F.; Kwolek, Christopher J.; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2011 VL 53 SU S BP 93S EP 94S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 774TY UT WOS:000291410700180 ER PT J AU Goodney, PP Scali, ST Stone, DH Patel, V Eslami, M Wallaert, J Shaw, P Cronenwett, JL AF Goodney, Philip P. Scali, Salvatore T. Stone, David H. Patel, Virenda Eslami, Mohammad Wallaert, Jessica Shaw, Palma Cronenwett, Jack L. TI Impact of Surgeon Practice Pattern in Shunt Use during CEA for Contralateral Carotid Occlusion SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 16-18, 2011 CL Chicago, IL SP Soc Vasc Surg C1 [Goodney, Philip P.; Stone, David H.; Wallaert, Jessica; Cronenwett, Jack L.] Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, Lebanon, NH 03766 USA. [Patel, Virenda] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shaw, Palma] Brigham & Womens Hosp, Boston, MA 02115 USA. [Scali, Salvatore T.] Univ Florida, Gainesville, FL USA. [Eslami, Mohammad] Univ Massachusetts, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2011 VL 53 SU S BP 94S EP 95S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 774TY UT WOS:000291410700182 ER PT J AU Patel, VI Ergul, E Conrad, MF Cambria, M LaMuraglia, GM Kwolek, CJ Brewster, DC Cambria, RP AF Patel, Virendra I. Ergul, Emel Conrad, Mark F. Cambria, Matthew LaMuraglia, Glenn M. Kwolek, Christopher J. Brewster, David C. Cambria, Richard P. TI Continued favorable results with open surgical repair of type IV thoracoabdominal aortic aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Vascular-Surgery CY JUN 10-14, 2010 CL Boston, MA SP Soc Vasc Surg ID CEREBROSPINAL-FLUID DRAINAGE; REDUCES PARAPLEGIA; EVOKED-POTENTIALS; RENAL-FAILURE; MORTALITY; SURGERY; TRIAL; OPERATIONS; EVOLUTION; PERFUSION AB Objectives: Type IV thoracoabdominal aortic aneurysm (TAAA) repair, despite low risk of spinal cord ischemia (SCI), is reported to have significant morbidity and mortality. This has led some to apply adjuncts (eg, extracorporeal circulation) used in more extensive TAAA repair or to consider alternative approaches, such as hybrid operations. We have used a consistent, simplified surgical approach to type IV TAAA, and the goal of the present study is to review experience over 2 decades with such treatment and to identify correlates of surgical morbidity. Methods: All type IV repairs at Massachusetts General Hospital from January 1989 through September 2009 were evaluated for clinical features, technical operative details, and 30-day outcomes. Logistic regression identified predictors of morbidity. Survival was assessed using Kaplan-Meier analysis. Results: A total of 179 patients underwent type IV repair, with elective repair in 156 (87%) and urgent in 23 (13%). The clamp-and-sew technique was used for all operations, with routine hypothermic renal perfusion. Clinical features were age 73 +/- 8 years, coronary artery disease in 89 (50%), and creatinine level > 1.8 mg/dL defining chronic renal insufficiency (CRI) in 32 (18%). Operative reconstruction in 166 (93%) consisted of one beveled proximal anastomosis incorporating the descending thoracic aorta, celiac, superior mesenteric artery, and right renal arteries origins (mean visceral clamp time, 36 +/- 12 minutes) and a side-arm graft to the left renal artery. Technical details included previous abdominal aortic aneurysm (AAA) repair in 52 (29%), operative time of 290 +/- 90 min, estimated blood loss of 2.7 +/- 1.4 L, and splenectomy in 57 (32%). The 30-day outcomes were death in 5 (2.8%), myocardial infarction in 6 (3.4%), hemodialysis in 5 (2.8%), and any degree of SCI in 4 (2.2%). Regression analysis identified a history of CRI as an independent predictor of postoperative complication or death (odds ratio, 3.4; 95% confidence interval, 1.4-8). Survival rates at 1, 5, and 10 years were 89% +/- 2%, 62% +/- 4%, and 36% +/- 5%, respectively. Conclusions: A simplified operative approach for type IV TAAA repair is associated with favorable perioperative results. These data refute the need for surgical adjuncts commonly applied in more extensive TAAA and indicate that the hybrid operation is an illogical posture. CRI should figure prominently in clinical decision making. Long-term survival equates that observed after routine AAA repair. (J Vase Surg 2011;53:1492-8.) C1 [Patel, Virendra I.; Ergul, Emel; Conrad, Mark F.; Cambria, Matthew; LaMuraglia, Glenn M.; Kwolek, Christopher J.; Brewster, David C.; Cambria, Richard P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Patel, VI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,Wang ACC 440, Boston, MA 02114 USA. EM vpatel4@partners.org NR 41 TC 13 Z9 13 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 JUN PY 2011 VL 53 IS 6 BP 1492 EP 1498 DI 10.1016/j.jvs.2011.01.070 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 774TX UT WOS:000291410600007 PM 21514769 ER PT J AU Kennealey, PT Elias, N Hertl, M Ko, DSC Saidi, RF Markmann, JF Smoot, EE Schoenfeld, DA Kawai, T AF Kennealey, Peter T. Elias, Nahel Hertl, Martin Ko, Dicken S. C. Saidi, Reza F. Markmann, James F. Smoot, Elizabeth E. Schoenfeld, David A. Kawai, Tatsuo TI A prospective, randomized comparison of bovine carotid artery and expanded polytetrafluoroethylene for permanent hemodialysis vascular access SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID GRAFT ARTERIOVENOUS-FISTULA; WALL EPTFE GRAFTS; 3-YEAR FOLLOW-UP; MULTICENTER EVALUATION; PTFE GRAFT; HETEROGRAFT; EXPERIENCE; APPLICATIONS/; STANDARD; PATENCY AB Background: Many patients on hemodialysis do not have adequate anatomy for native arteriovenous fistulas. In these patients, synthetic conduits remain an alternative option for permanent hemodialysis access. We sought to compare the standard cuffed expanded polytetrafluoroethylene (ePTFE) graft with the bovine carotid artery (BCA) graft. Methods: This was a prospective, randomized controlled trial that was set in an academic medical center. We enrolled 26 patients in the BCA group and 27 patients in the ePTFE group. Primary, assisted primary, and secondary patency were calculated using the Kaplan-Meier method. Complications were monitored and are reported. Results: Although there was no significant difference in secondary patency rates, primary and assisted primary patency rates were significantly higher in BCA than in the ePTFE grafts (60.5% vs 10.1% and 60.5% vs 20.8% at I year, respectively). The BCA graft survival advantage was most profound in the upper arm grafts with significantly higher primary and assisted patency rates (P < .0001 and .0005, respectively). The total number of interventions (upper arm grafts) and total number of angioplasties (overall and upper arm) required to maintain patency were significantly fewer in the BCA group. The most common complication was graft thrombosis which occurred 0.34 +/- 0.09 times per patient year in the BCA group compared to 0.77 +/- 0.16 times per patient year in the ePTFE group, P = .01. Conclusion: The BCA graft is an excellent option for patients on hemodialysis that are not suitable for native arteriovenous fistulas, as these grafts required fewer interventions than the ePTFE grafts to maintain patency. (J Vase Surg 2011;53:1640-8.) C1 [Kennealey, Peter T.; Elias, Nahel; Hertl, Martin; Ko, Dicken S. C.; Saidi, Reza F.; Markmann, James F.; Kawai, Tatsuo] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Div Transplantat, Boston, MA 02115 USA. [Smoot, Elizabeth E.; Schoenfeld, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02115 USA. RP Kennealey, PT (reprint author), 2555 S Downing St,Suite 130, Denver, CO 80210 USA. EM pkennealey@gmail.com FU Artegraft, NCT [01021839] FX This work was funded in part by a research grant from Artegraft, NCT# 01021839. NR 33 TC 13 Z9 14 U1 0 U2 8 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 JUN PY 2011 VL 53 IS 6 BP 1640 EP 1648 DI 10.1016/j.jvs.2011.02.008 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 774TX UT WOS:000291410600028 PM 21609797 ER PT J AU Glide-Hurst, CK Ionascu, D Berbeco, R Yan, D AF Glide-Hurst, Carri K. Ionascu, Dan Berbeco, Ross Yan, Di TI Coupling surface cameras with on-board fluoroscopy: A feasibility study SO MEDICAL PHYSICS LA English DT Article DE surface imaging; respiratory gating; fluoroscopy; respiratory motion; lung cancer ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; TUMOR-TRACKING SYSTEM; CELL LUNG-CANCER; MULTILEAF COLLIMATOR; GATED RADIOTHERAPY; EXTERNAL MARKERS; ORGAN MOTION; ACCURACY; CT; INTRAFRACTION AB Purpose: To investigate the feasibility of using three-dimensional surface imaging cameras as an external surrogate of tumor motion through a temporal synchronization with kV imaging. Methods: To obtain an "x-ray on" signal from the on-board kV fluoroscopy system (XVI, Elekta), a hardware controller (Gate Controller) was interfaced between the kV fluoroscopy and Gate CT (VisionRT Ltd., London) computers. First, phantom experiments were performed using a programmable respiratory motion platform (sinusoidal motion, period = 3-5 s). The platform included a chest-wall component (A-P amplitude = 1 cm) tracked with the surface camera, while tumorlike objects translated in the superior-inferior direction were tracked using kV fluoroscopy (300 frames, frequency similar to 5.5 fps). Accuracy of tracking the chest-wall platform was assessed, and the latency of the system was characterized by performing linear regression between the peak times obtained from Gate CT and fluoroscopy. Increasing the complexity of experiments, tumor displacement curves from three patients were simulated using synchronous tumor-abdomen data (RTRT). Our approach was further validated by imaging four free-breathing lung cancer patients with simultaneous Gate CT and kV fluoroscopy for approximately 55 s. Consideration was also given to varied sizes and locations of the tracked region of interest on the patient surface. Results: For simple sinusoidal curves, measured amplitude (peak-to-peak) was 1.005 +/- 0.003 cm, 1.013 +/- 0.003 cm, and 1.003 +/- 0.005 cm for periods of 5, 4, and 3.3 s, respectively, demonstrating an excellent agreement with the actual chest platform amplitude of 1.0 cm. Period measurements were within 0.2% of actual using the surface cameras and within 0.9% of actual value using fluoroscopy. For the sinusoidal motion, the system latency was 0.64 +/- 0.02 s. This was further validated for the simulated tumor motion from three patients (latency = 0.65 +/- 0.03 s). Five of the nine patient fractions studied showed the associations between the abdomen and tumor were equivalent or better (Pearson r = 0.93-0.98) than those observed between the diaphragm and tumor (Pearson r = 0.89-0.95). A repeat analysis of five different tracked surfaces on the same patient further demonstrated strong agreement with the diaphragm and tumor, although no improvement in association strength was observed with increased size of region of interest. Conclusions: The feasibility of using surface imaging cameras to track the patient's abdomen as an external surrogate, while using kV imaging to track internal anatomy in synchrony, has been demonstrated. With further validation through additional patient studies to confirm these findings, gated radiation therapy treatments using surface imaging cameras as the external surrogate can be facilitated. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3581057] C1 [Glide-Hurst, Carri K.] Henry Ford Hlth Syst, Dept Radiat Oncol, Detroit, MI 48202 USA. [Ionascu, Dan; Yan, Di] William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI 48073 USA. [Berbeco, Ross] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Berbeco, Ross] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Glide-Hurst, CK (reprint author), Henry Ford Hlth Syst, Dept Radiat Oncol, Detroit, MI 48202 USA. EM churst2@hfhs.org NR 28 TC 10 Z9 10 U1 0 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2011 VL 38 IS 6 BP 2937 EP 2947 DI 10.1118/1.3581057 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 774RZ UT WOS:000291405200012 PM 21815367 ER PT J AU Guerin, B Cho, S Chun, SY Zhu, X Alpert, NM El Fakhri, G Reese, T Catana, C AF Guerin, B. Cho, S. Chun, S. Y. Zhu, X. Alpert, N. M. El Fakhri, G. Reese, T. Catana, C. TI Nonrigid PET motion compensation in the lower abdomen using simultaneous tagged-MRI and PET imaging SO MEDICAL PHYSICS LA English DT Article DE fully 3D reconstruction; motion correction; simultaneous PET-MRI acquisitions; tagged-MRI ID GATED PET; ATTENUATION CORRECTION; MAGNETIC-RESONANCE; SPATIAL MODULATION; OPTICAL-FLOW; 3D PET; IMAGES; RECONSTRUCTION; REDUCTION; TRACKING AB Purpose: We propose a novel approach for PET respiratory motion correction using tagged-MRI and simultaneous PET-MRI acquisitions. Methods: We use a tagged-MRI acquisition followed by motion tracking in the phase domain to estimate the nonrigid deformation of biological tissues during breathing. In order to accurately estimate motion even in the presence of noise and susceptibility artifacts, we regularize the traditional HARP tracking strategy using a quadratic roughness penalty on neighboring displacement vectors (R-HARP). We then incorporate the motion fields estimated with R-HARP in the system matrix of an MLEM PET reconstruction algorithm formulated both for sinogram and list-mode data representations. This approach allows reconstruction of all detected coincidences in a single image while modeling the effect of motion both in the emission and the attenuation maps. At present, tagged-MRI does not allow estimation of motion in the lungs and our approach is therefore limited to motion correction in soft tissues. Since it is difficult to assess the accuracy of motion correction approaches in vivo, we evaluated the proposed approach in numerical simulations of simultaneous PET-MRI acquisitions using the NCAT phantom. We also assessed its practical feasibility in PET-MRI acquisitions of a small deformable phantom that mimics the complex deformation pattern of a lung that we imaged on a combined PET-MRI brain scanner. Results: Simulations showed that the R-HARP tracking strategy accurately estimated realistic respiratory motion fields for different levels of noise in the tagged-MRI simulation. In simulations of tumors exhibiting increased uptake, contrast estimation was 20% more accurate with motion correction than without. Signal-to-noise ratio (SNR) was more than 100% greater when performing motion-corrected reconstruction which included all counts, compared to when reconstructing only coincidences detected in the first of eight gated frames. These results were confirmed in our proof-of-principle PET-MRI acquisitions, indicating that our motion correction strategy is accurate, practically feasible, and is therefore ready to be tested in vivo. Conclusions: This work shows that PET motion correction using motion fields measured with tagged-MRI in simultaneous PET-MRI acquisitions can be made practical for clinical application and that doing so has the potential to remove motion blur in whole-body PET studies of the torso. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3589136] C1 [Guerin, B.; Cho, S.; Chun, S. Y.; Zhu, X.; Alpert, N. M.; El Fakhri, G.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Reese, T.; Catana, C.] Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP El Fakhri, G (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, 55 Fruit St, Boston, MA 02114 USA. EM elfakhri@pet.mgh.harvard.edu RI Chun, Se Young/B-6653-2013; Guerin, Bastien/P-1412-2014; OI Chun, Se Young/0000-0001-8739-8960 NR 54 TC 59 Z9 60 U1 0 U2 10 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2011 VL 38 IS 6 BP 3025 EP 3038 DI 10.1118/1.3589136 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 774RZ UT WOS:000291405200021 PM 21815376 ER PT J AU Winey, B Wagar, M Ebe, K Popple, R Lingos, T Sher, D Court, L AF Winey, Brian Wagar, Matthew Ebe, Kazuyu Popple, Richard Lingos, Tania Sher, David Court, Laurence TI Effect of respiratory trace shape on optimal treatment margin SO MEDICAL PHYSICS LA English DT Article DE internal margins; respiratory motion; IMRT; VMAT ID MOTION; RADIOTHERAPY; ERRORS AB Purpose: To evaluate the effect of target trajectory shape on the optimal treatment margin. Methods: Intensity-modulated radiation therapy and volumetric modulated arc therapy plans were created for three spherical targets (3, 5, and 7 cm diameter) simulated in exhalation phases, each with margins of 2, 4, 6, 8, and 10 mm to account for motion. The plans were delivered to a stationary 2D ion chamber array, and dose movies were obtained of the delivered doses. The dose movie frames were then displaced to simulate different respiratory traces. Five traces were used: sin(2), sin(4), sin(6), and two patient traces. The optimal margin was defined as the margin for which the dose delivered to 95% of the target was closest to that obtained with no margin or motion. The equivalent uniform dose was also investigated as an alternative cost function. Results: The optimal margin was always smaller than the peak-to-peak motion. When the respiratory trace spent less time in the inhale phases, the optimal margin was consistently smaller than when more time was spent in the inhale phases. The target size and treatment modality also affected the optimal margin. Conclusions: The necessary margin for targets that spend less time in the exhale phase (sin(6)) is 2-4 mm smaller than for targets that spend equal time in the inhale and exhale phases (sin). (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3592649] C1 [Winey, Brian; Wagar, Matthew; Lingos, Tania; Sher, David; Court, Laurence] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Winey, Brian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Ebe, Kazuyu] JA Jouetsu Hosp, Joetsu 9430171, Japan. [Popple, Richard] Univ Alabama, Dept Radiat Oncol, Birmingham, AL 35249 USA. [Court, Laurence] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. RP Winey, B (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. EM winey.brian@mgh.harvard.edu OI Popple, Richard/0000-0003-1252-738X NR 11 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2011 VL 38 IS 6 BP 3125 EP 3129 DI 10.1118/1.3592649 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 774RZ UT WOS:000291405200031 PM 21815386 ER PT J AU Yue, Y Aristophanous, M Rottmann, J Berbeco, RI AF Yue, Yong Aristophanous, Michalis Rottmann, Joerg Berbeco, Ross I. TI 3-D fiducial motion tracking using limited MV projections in arc therapy SO MEDICAL PHYSICS LA English DT Article DE VMAT; maximum a posteriori; maximum likelihood; prostate; statistical method; image guidance ID INTENSITY-MODULATED RADIOTHERAPY; REAL-TIME; IMRT AB Purpose: In-treatment fiducial tracking has recently received attention as a method for improving treatment accuracy, dose conformity, and sparing of healthy tissue. 3-D fiducial localization in arc-radiotherapy remains challenging due to the motion of targets and the complexity of arc deliveries. We propose a novel statistical method for estimating 3-D fiducial motion using limited 2-D mega-voltage (MV) projections. Methods: 3-D fiducial motion was estimated by a maximum a posteriori (MAP) approach to integrating information of fiducial projections with prior knowledge of target motion. To obtain the imaging geometries, short sequences of MV projections were selected in which fiducials were continuously visible. The MAP algorithm estimated the 3-D motion by maximizing the probability of displacement of fiducials in the sequences. Prior knowledge of target motion from a large statistical sample was built into the model to enhance the accuracy of estimation. In the case that a motion prior was unavailable, the algorithm can be simplified to the maximum likelihood (ML) approach. To compare tracking performance, a multiprojection geometric method was also presented by extending the typical two-project ion geometric estimation approach. The algorithms were evaluated using clinical prostate motion traces, and the performance was measured in quality indices and statistical evaluation. Results: The results showed that the MAP method significantly outperforms the geometric method in all measures. In our simulations, the MAP method achieved an accuracy of less than 1 mm RMS error using only five continuous projections, whereas the geometric method required 15 projections to achieve a similar result. Conclusions: The approach presented can accurately estimate tumor motion using a limited number of continuous projections. The MAP motion estimation is superior to both the ML and geometric estimation methods. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3584197] C1 [Yue, Yong; Aristophanous, Michalis; Rottmann, Joerg; Berbeco, Ross I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiat Oncol, Boston, MA 02115 USA. RP Yue, Y (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM yyue@lroc.harvard.edu FU Varian Medical Systems, Inc. FX The authors would like to thank Dr. Katja Langen for generously providing the clinical prostate motion traces used in this study. This project was supported, in part, by a research grant from Varian Medical Systems, Inc. NR 17 TC 4 Z9 5 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2011 VL 38 IS 6 BP 3222 EP 3231 DI 10.1118/1.3584197 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 774RZ UT WOS:000291405200042 PM 21815397 ER PT J AU Hernandez-Davies, JE Zape, JP Landaw, EM Tan, XL Presnell, A Griffith, D Heinrich, MC Glaser, KB Sakamoto, KM AF Hernandez-Davies, Jenny E. Zape, Joan P. Landaw, Elliot M. Tan, Xiaolin Presnell, Ajia Griffith, Diana Heinrich, Michael C. Glaser, Keith B. Sakamoto, Kathleen M. TI The Multitargeted Receptor Tyrosine Kinase Inhibitor Linifanib (ABT-869) Induces Apoptosis through an Akt and Glycogen Synthase Kinase 3 beta-Dependent Pathway SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID LEUKEMIC-CELLS; DOWN-REGULATION; AML CELLS; FLT3; ACTIVATION; MCL-1; PHOSPHORYLATION; TRANSFORMATION; DAUNORUBICIN; CYTARABINE AB The FMS-like receptor tyrosine kinase 3 (FLT3) plays an important role in controlling differentiation and proliferation of hematopoietic cells. Activating mutations in FLT3 occur in patients with acute myeloid leukemia (AML; 15%-35%), resulting in abnormal cell proliferation. Furthermore, both adult and pediatric patients with AML harboring the FLT3 internal tandem duplication (ITD) mutation have a poor prognosis. Several inhibitors have been developed to target mutant FLT3 for the treatment of AML, yet the molecular pathways affected by drug inhibition of the mutated FLT3 receptor alone have not been characterized as yet. Linifanib (ABT-869) is a multitargeted tyrosine kinase receptor inhibitor that suppresses FLT3 signaling. In this article, we show that treatment with linifanib inhibits proliferation and induces apoptosis in ITD mutant cells in vitro and in vivo. We show that treatment with linifanib reduces phosphorylation of Akt and glycogen synthase kinase 3 beta (GSK3 beta). In addition, we show that inhibition of GSK3b decreases linifanib-induced apoptosis. This study shows the importance of GSK3 beta as a potential target for AML therapy, particularly in patients with FLT3 ITD mutations. Mol Cancer Ther; 10(6); 949-59. (C)2011 AACR. C1 [Hernandez-Davies, Jenny E.; Zape, Joan P.; Sakamoto, Kathleen M.] Univ Calif Los Angeles, Mattel Childrens Hosp UCLA, Jonsson Comprehens Canc Ctr, Div Hematol Oncol,Gwynne Hazen Cherry Mem Labs, Los Angeles, CA 90095 USA. [Hernandez-Davies, Jenny E.; Sakamoto, Kathleen M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Sakamoto, Kathleen M.] Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA. [Sakamoto, Kathleen M.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. [Landaw, Elliot M.] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90095 USA. [Tan, Xiaolin] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA. [Presnell, Ajia; Griffith, Diana; Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. [Presnell, Ajia; Griffith, Diana; Heinrich, Michael C.] OHSU Knight Canc Inst, Portland, OR USA. [Glaser, Keith B.] Abbott Labs, Abbott Pk, IL 60064 USA. RP Sakamoto, KM (reprint author), Univ Calif Los Angeles, Mattel Childrens Hosp UCLA, Jonsson Comprehens Canc Ctr, Div Hematol Oncol,Gwynne Hazen Cherry Mem Labs, Los Angeles, CA 90095 USA. EM ksakamoto@mednet.ucla.edu FU Abbott Laboratories, Inc.; Genentech, Inc.; NIH [HL75826, HL83077]; William Lawrence and Blanche Hughes Foundation; St. Baldrick's Foundation; Department of Veterans Affairs; Leukemia and Lymphoma Society FX K.M. Sakamoto received a commercial research grant from Abbott Laboratories, Inc., and received other commercial research support from Genentech, Inc. M.C. Heinrich has equity interest in Molecular M.D.; K.M. Sakamoto is supported by NIH grants HL75826 and HL83077, the William Lawrence and Blanche Hughes Foundation, and the St. Baldrick's Foundation. K.M. Sakamoto is a scholar of the Leukemia and Lymphoma Society. M.C. Heinrich is supported, in part, by a Merit Review grant from the Department of Veterans Affairs and a SCOR grant from the Leukemia and Lymphoma Society. NR 34 TC 11 Z9 13 U1 0 U2 5 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 JUN PY 2011 VL 10 IS 6 BP 949 EP 959 DI 10.1158/1535-7163.MCT-10-0904 PG 11 WC Oncology SC Oncology GA 775AI UT WOS:000291428000004 PM 21471285 ER PT J AU DeFeo, EM Wu, CL McDougal, WS Cheng, LL AF DeFeo, Elita M. Wu, Chin-Lee McDougal, W. Scott Cheng, Leo L. TI A decade in prostate cancer: from NMR to metabolomics SO NATURE REVIEWS UROLOGY LA English DT Review ID MAGNETIC-RESONANCE-SPECTROSCOPY; HR-MAS SPECTROSCOPY; PROTON MR SPECTROSCOPY; HORMONE-DEPRIVATION THERAPY; DIGITAL RECTAL EXAMINATION; PRIOR NEGATIVE BIOPSY; HUMAN SEMINAL FLUID; IN-VIVO; ENDORECTAL MR; RADICAL PROSTATECTOMY AB Over the past 30 years, continuous progress in the application of nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance spectroscopic imaging (MRSI) to the detection, diagnosis and characterization of human prostate cancer has turned what began as scientific curiosity into a useful clinical option. In vivo MRSI technology has been integrated into the daily care of prostate cancer patients, and innovations in ex vivo methods have helped to establish NMR-based prostate cancer metabolomics. Metabolomic and multimodality imaging could be the future of the prostate cancer clinic-particularly given the rationale that more accurate interrogation of a disease as complex as human prostate cancer is most likely to be achieved through paradigms involving multiple, instead of single and isolated, parameters. The research and clinical results achieved through in vivo MRSI and ex vivo NMR investigations during the first 11 years of the 21st century illustrate areas where these technologies can be best translated into clinical practice. C1 [DeFeo, Elita M.; Cheng, Leo L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [McDougal, W. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. RP Cheng, LL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM cheng@nmr.mgh.harvard.edu FU NIH [CA115746, CA115746S2, CA141139] FX We thank Ms J. Fordham for editorial assistance. Grant funding support: NIH CA115746, CA115746S2, and CA141139. NR 166 TC 27 Z9 27 U1 0 U2 33 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4812 J9 NAT REV UROL JI Nat. Rev. Urol. PD JUN PY 2011 VL 8 IS 6 BP 301 EP 311 DI 10.1038/nrurol.2011.53 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 776OO UT WOS:000291546200004 PM 21587223 ER PT J AU Ringman, JM Taylor, K Teng, E Coppola, G Gylys, K AF Ringman, J. M. Taylor, K. Teng, E. Coppola, G. Gylys, K. TI LONGITUDINAL CHANGE IN CSF BIOMARKERS IN A PRESYMPTOMATIC CARRIER OF AN APP MUTATION SO NEUROLOGY LA English DT Editorial Material ID ALZHEIMER-DISEASE; MARKERS C1 [Ringman, J. M.] Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Dept Neurol, Los Angeles, CA 90095 USA. [Taylor, K.; Gylys, K.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. [Teng, E.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Ringman, JM (reprint author), Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Dept Neurol, 10911 Weyburn Ave,200, Los Angeles, CA 90095 USA. EM jringman@mednet.ucla.edu FU NCATS NIH HHS [UL1 TR000124]; NCRR NIH HHS [UL1 RR033176, M01-RR00865]; NIA NIH HHS [K08 AG-22228, P50 AG-16570] NR 7 TC 10 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2011 VL 76 IS 24 BP 2124 EP 2125 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 777BR UT WOS:000291588800018 PM 21562250 ER PT J AU Jensen, JH Falangola, MF Hu, CX Tabesh, A Rapalino, O Lo, C Helpern, JA AF Jensen, Jens H. Falangola, Maria F. Hu, Caixia Tabesh, Ali Rapalino, Otto Lo, Calvin Helpern, Joseph A. TI Preliminary observations of increased diffusional kurtosis in human brain following recent cerebral infarction SO NMR IN BIOMEDICINE LA English DT Article DE ischemia; stroke; diffusion; brain; kurtosis; DKI; DTI; MRI ID GAUSSIAN WATER DIFFUSION; ENDOPLASMIC-RETICULUM; ISCHEMIC-STROKE; NEURONAL DEATH; RAT-BRAIN; MODEL; TISSUES AB By application of the MRI method of diffusional kurtosis imaging, a substantially increased diffusional kurtosis was observed within the cerebral ischemic lesions of three stroke subjects, 13-26 h following the onset of symptoms. This increase is interpreted as probably reflecting a higher degree of diffusional heterogeneity in the lesions when compared with normal-appearing contralateral tissue. In addition, for two of the subjects with white matter infarcts, the increase had a strong fiber tract orientational dependence. It is proposed that this effect is consistent with a large drop in the intra-axonal diffusivity, possibly related to either axonal varicosities or alterations associated with the endoplasmic reticulum. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Jensen, Jens H.; Falangola, Maria F.; Hu, Caixia; Tabesh, Ali; Lo, Calvin; Helpern, Joseph A.] NYU, Sch Med, Dept Radiol, Ctr Biomed Imaging, New York, NY 10016 USA. [Jensen, Jens H.; Helpern, Joseph A.] NYU, Sch Med, Dept Physiol & Neurosci, New York, NY 10016 USA. [Falangola, Maria F.; Hu, Caixia; Helpern, Joseph A.] Nathan S Kline Inst Psychiat Res, Ctr Adv Brain Imaging, Orangeburg, NY 10962 USA. [Rapalino, Otto] Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Div, Boston, MA 02114 USA. [Helpern, Joseph A.] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. RP Jensen, JH (reprint author), NYU, Sch Med, Dept Radiol, Ctr Biomed Imaging, 660 1st Ave,4th Floor, New York, NY 10016 USA. EM jj33@nyu.edu FU National Institutes of Health [1R01AG027852, 1R01EB007656]; Litwin Foundation for Alzheimer's Research FX We thank Dr Steven Levine for helpful comments. This work was supported by the National Institutes of Health (contract/grant numbers 1R01AG027852 and 1R01EB007656) and the Litwin Foundation for Alzheimer's Research. NR 27 TC 72 Z9 82 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD JUN PY 2011 VL 24 IS 5 BP 452 EP 457 DI 10.1002/nbm.1610 PG 6 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 777EA UT WOS:000291597200002 PM 20960579 ER PT J AU Traugott, KA Echevarria, K Maxwell, P Green, K Lewis, JS AF Traugott, Kristi A. Echevarria, Kelly Maxwell, Pamela Green, Kay Lewis, James S., II TI Monotherapy or Combination Therapy? The Pseudomonas aeruginosa Conundrum SO PHARMACOTHERAPY LA English DT Review DE Pseudomonas aeruginosa; combination therapy; bacteremia; ventilator-associated pneumonia; monotherapy ID VENTILATOR-ASSOCIATED PNEUMONIA; BLOOD-STREAM INFECTIONS; BETA-LACTAM MONOTHERAPY; GRAM-NEGATIVE BACTEREMIA; INTENSIVE-CARE UNITS; ANTIMICROBIAL THERAPY; ANTIBIOTIC-THERAPY; TIME-KILL; RETROSPECTIVE ANALYSIS; STAPHYLOCOCCUS-AUREUS AB The use of combination antibiotic therapy for severe pseudomonal infections is a standard practice in many hospitals; however, the data supporting its use are somewhat unclear. Possible benefits of combination therapy for Pseudomonas aeruginosa infections include in vitro antibiotic synergy, prevention of the emergence of bacterial resistance while receiving therapy, and improved adequacy of empiric therapy. Unfortunately, the potential disadvantages are also considerable, the most worrisome of which are drug toxicity and creation of multidrug-resistant organisms in the environment. Many in vitro and animal studies have attempted to shed light on this clinically challenging issue; however, these studies have often yielded conflicting results and used different study methods, which limits the clinical utility of the results. Clinical studies have also attempted to clarify this issue, particularly in patients with serious pseudomonal infections such as bacteremia and ventilator-associated pneumonia, but again, often resulted in conflicting conclusions. Thus, we performed a MEDLINE search (1950-May 2010) of clinical and in vitro studies evaluating the use of antibiotic combination therapy and monotherapy for bacteremia and pneumonia due to P. aeruginosa. Although a clear answer still eludes this controversy, combination therapy for seriously ill patients suspected of having pseudomonal infection has been shown, with considerable evidence, to improve the likelihood of an active agent being included in the initial antibiotic regimen of these patients. The clinical status of the patient and true likelihood of encountering a multidrug-resistant organism should be evaluated before deciding on empiric combination therapy. Future research may be able to better identify which patient populations might receive the most benefit from combination therapy rather than using combination therapy for everyone at risk for these infections. C1 [Maxwell, Pamela; Green, Kay; Lewis, James S., II] Univ Hlth Syst, Dept Pharm Serv, San Antonio, TX 78229 USA. [Echevarria, Kelly] S Texas Vet Hlth Care Syst, Dept Pharm Serv, San Antonio, TX USA. [Traugott, Kristi A.] Ochsner Med Ctr, Dept Pharm Serv, New Orleans, LA USA. RP Lewis, JS (reprint author), Univ Hlth Syst, Dept Pharm Serv, 4502 Med Dr,MS 102-1, San Antonio, TX 78229 USA. EM James.Lewis@uhs-sa.com NR 57 TC 28 Z9 29 U1 0 U2 12 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUN PY 2011 VL 31 IS 6 BP 598 EP 608 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774HE UT WOS:000291375500009 PM 21923444 ER PT J AU Kleespies, PM Van Orden, KA Bongar, B Bridgeman, D Bufka, LF Galper, DI Hillbrand, M Yufit, RI AF Kleespies, Phillip M. Van Orden, Kimberly A. Bongar, Bruce Bridgeman, Diane Bufka, Lynn F. Galper, Daniel I. Hillbrand, Marc Yufit, Robert I. TI Psychologist Suicide: Incidence, Impact, and Suggestions for Prevention, Intervention, and Postvention SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE psychologist suicide; colleague suicide; impact of psychologist suicide; colleague assistance; self-care ID OCCUPATION; IMPAIRMENT; DOCTORS; ASSOCIATION; EXPERIENCES; DEPRESSION; THERAPISTS; US AB Psychologist practitioners are not immune to certain mental health problems, including suicidality, for which they provide services. In the aftermath of two recent psychologist suicides, the American Psychological Association's Advisory Committee on Colleague Assistance (ACCA) initiated the formation of a conjoint ad hoc committee consisting of members from ACCA, the American Psychological Association (APA) Practice Directorate, and the Section on Clinical Emergencies and Crises (Section VII of APA's Division 12) to investigate the incidence of psychologist suicide and its impact on colleagues, students or interns, patients or clients, and the profession. The committee reviewed the extant empirical literature on suicide rates for psychologists, evaluated unpublished data on psychologist suicide provided by the National Institute of Occupational Safety and Health (NIOSH), interviewed colleague survivors, reviewed published case reports of the impact of therapist suicides, and linked their findings to the literature on professional distress, impairment, and self-care. The committee concluded that there is evidence suggestive of an elevated risk of suicide for psychologists in past decades. It further concluded that there is a need for further research to confirm if there is a heightened risk of suicide for psychologists in the present day and to determine factors that might contribute to such risk. Accounts from colleague-survivors suggest that the impact of a psychologist's suicide can affect many people including family, colleagues, students, and patients or clients. This article offers suggestions for possible preventive approaches, for intervention with potentially at-risk colleagues, and for postvention efforts in the wake of a colleague suicide. C1 [Kleespies, Phillip M.] VA Boston Healthcare Syst, Psychol Serv 116 B, Boston, MA 02130 USA. [Van Orden, Kimberly A.] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14627 USA. [Bongar, Bruce] Palo Alto Univ, Pacific Grad Sch Psychol, Palo Alto, CA USA. [Bridgeman, Diane] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. [Bufka, Lynn F.; Galper, Daniel I.] Amer Psychol Assoc, Practice Directorate, Washington, DC 20036 USA. [Hillbrand, Marc] Connecticut Valley Hosp, Middletown, CT USA. [Yufit, Robert I.] Northwestern Univ, Sch Med, Evanston, IL 60208 USA. RP Kleespies, PM (reprint author), VA Boston Healthcare Syst, Psychol Serv 116 B, 150 S Huntington Ave, Boston, MA 02130 USA. EM phillip.kleespies@va.gov OI Van Orden, Kimberly/0000-0001-9439-401X FU NIMH NIH HHS [T32 MH020061, T32 MH020061-10] NR 49 TC 4 Z9 4 U1 0 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 EI 1939-1323 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD JUN PY 2011 VL 42 IS 3 BP 244 EP 251 DI 10.1037/a0022805 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 776DY UT WOS:000291515900006 PM 21731175 ER PT J AU Grudzen, CR Meeker, D Torres, JM Du, QL Morrison, RS Andersen, RM Gelberg, L AF Grudzen, Corita R. Meeker, Daniella Torres, Jacqueline M. Du, Qingling Morrison, R. Sean Andersen, Ronald M. Gelberg, Lillian TI Comparison of the Mental Health of Female Adult Film Performers and Other Young Women in California SO PSYCHIATRIC SERVICES LA English DT Article ID GREATER SYDNEY AREA; SEX WORKERS; SUBSTANCE-ABUSE; PUBLIC-HEALTH; LOS-ANGELES; VIOLENCE; INFECTIONS; DEPRESSION; OCCUPATION; INDUSTRY AB Objective: This study compared self-reported mental health status and current depression of female adult film performers and other young women. Methods: A cross-sectional structured online survey adapted from the California Women's Health Survey (CWHS) was self-administered to a convenience sample of 134 current female adult film performers via the Internet. Bivariate and multivariate analyses were used to compare data for these women with data for 1,773 women of similar ages who responded to the 2007 CWHS. Main outcome measures were self-reported mental health status, measured with the Behavioral Risk Factor Surveillance Survey core-instrument quality-of-life questions, and current depression, measured with the Patient Health Questionnaire-8. Results: Performers reported a mean of 7.2 days of poor mental health in the past 30 days, compared with 4.8 days for CWHS respondents, and 33% met criteria for current depression, compared with 13% of CWHS respondents (p<.01). As children, the adult film performers were more likely to have been victims of forced sex (37% compared with 13% of CWHS respondents), to have lived in poverty (24% and 12%), and to have been placed in foster care (21% and 4%) (p<.01). In the past 12 months, 50% of the performers reported living in poverty and 34% reported experiencing domestic violence, compared with 36% and 6%, respectively, of CWHS respondents (p<.01). As adults, 27% had experienced forced sex, compared with 9% of CWHS respondents (p<.01). Conclusions: Female adult film performers have significantly worse mental health and higher rates of depression than other California women of similar ages. (Psychiatric Services 62: 639-645, 2011) C1 [Grudzen, Corita R.] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Grudzen, Corita R.; Du, Qingling; Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Morrison, R. Sean] James J Peters VA Med Ctr, Bronx, NY USA. [Meeker, Daniella] RAND Corp, Santa Monica, CA USA. [Torres, Jacqueline M.; Andersen, Ronald M.; Gelberg, Lillian] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Gelberg, Lillian] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA USA. RP Grudzen, CR (reprint author), Mt Sinai Sch Med, Dept Emergency Med, 1 Gustave Levy Pl,Box 1620, New York, NY 10029 USA. EM corita.grudzen@mssm.edu OI Meeker, Daniella/0000-0002-1034-7628; Grudzen, Corita/0000-0003-3039-8497 FU University of California Office of the President; National Institute on Aging [K24 AG022345] FX This project was supported by an Innovative, Developmental, Exploratory Award (IDEA) from the California HIV/AIDS Research Program, University of California Office of the President. The funding entity had no role in the design and conduct of the study; collection, management, analysis, and interpretation of data; and preparation, review, or approval of the manuscript. Dr. Morrison was supported by a Mid-Career Investigator Award in Patient Oriented Research (K24 AG022345) from the National Institute on Aging. The authors thank the California Women's Health Survey Work-group for providing access to the 2007 CWHS data set. NR 44 TC 3 Z9 3 U1 3 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUN PY 2011 VL 62 IS 6 BP 639 EP 645 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 774SL UT WOS:000291406600012 PM 21632733 ER PT J AU Barkley, RA Knouse, LE Murphy, KR AF Barkley, Russell A. Knouse, Laura E. Murphy, Kevin R. TI Correspondence and Disparity in the Self- and Other Ratings of Current and Childhood ADHD Symptoms and Impairment in Adults With ADHD SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE attention-deficit/hyperactivity disorder (ADHD); symptom rating; impairment rating; self- other disparity; adults ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; RELIABILITY; DEFINITION; VALIDITY; STUDENTS AB Experts recommend that clinicians evaluating adults for attention-deficit/hyperactivity disorder (ADHD) obtain information from others who know the patient well. The authors examined correspondence between the self- and other-ratings of ADHD symptoms and impairment using 3 groups of adults recruited on the basis of their severity of ADHD: ADHD diagnosis (n = 146), clinical controls self-referring for ADHD but not diagnosed (n = 97), and community controls (n = 109). The influences of diagnostic group, informant relationship, sex of participant, IQ, and comorbid anxiety and depression on self-informant disparities were also examined. Results indicated moderate to high agreement (.59-.80) between self and others on current functioning and slightly lower levels (.53-.75) between self- and parent ratings of childhood functioning. Examination of difference scores between self- and other ratings revealed small mean disparities (-0.1 to +5.0 points) but substantial variation (SDs = -2.4 to 8.9 points) for both current and childhood ratings. Clinic referrals not diagnosed with ADHD, particularly women, had higher disparities than was evident in the ADHD and community groups. Age, IQ, and education were not associated with disparities in most ratings. Higher anxiety, in contrast, was associated with greater disparities on all current and childhood measures of both ADHD and impairment. C1 [Barkley, Russell A.] Med Univ S Carolina, Dept Psychiat, Charleston, SC USA. [Knouse, Laura E.] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA. [Knouse, Laura E.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Murphy, Kevin R.] Adult ADHD Ctr Cent Massachusetts, Northborough, MA USA. RP Barkley, RA (reprint author), 1752 Greenspoint Court, Mt Pleasant, SC 29466 USA. EM drbarkley@russellbarkley.org FU NIMH NIH HHS [MH54509] NR 35 TC 26 Z9 27 U1 2 U2 25 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD JUN PY 2011 VL 23 IS 2 BP 437 EP 446 DI 10.1037/a0022172 PG 10 WC Psychology, Clinical SC Psychology GA 774HY UT WOS:000291377500014 PM 21381833 ER PT J AU Ciernik, IF Niemierko, A Harmon, DC Kobayashi, W Chen, YL Yock, T Ebb, DH Raskin, KA Liebsch, N Horniceck, FJ DeLaney, TF AF Ciernik, I. F. Niemierko, A. Harmon, D. C. Kobayashi, W. Chen, Y-L Yock, T. Ebb, D. H. Raskin, K. A. Liebsch, N. Horniceck, F. J. DeLaney, T. F. TI Proton-based radiotherapy for unresectable or incompletely resected osteosarcoma SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Meeting Abstract CT 17th Annual Meeting of the German-Society-for-Radiation-Oncology CY JUN 02-05, 2011 CL Wiesbaden, GERMANY SP German Soc Radiat Oncol C1 [Ciernik, I. F.] Stadt Klinikum Dessau, Dessau, Germany. [DeLaney, T. F.] Massachusetts Gen Hosp, Francis H Burr Proton Ctr, Boston, MA 02114 USA. [Niemierko, A.; Harmon, D. C.; Yock, T.; Ebb, D. H.; Raskin, K. A.; Horniceck, F. J.; DeLaney, T. F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD JUN PY 2011 VL 187 SU 1 BP 6 EP 6 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 772LU UT WOS:000291236200007 ER PT J AU Niemeyer, E Kamoun, WS Han, HS Gillissen, M Martin, J Lanning, R Bawendi, MG Munn, LL Fukuruma, D Duda, DG Dunst, J Jain, RK AF Niemeyer, E. Kamoun, W. S. Han, H. -S Gillissen, M. Martin, J. Lanning, R. Bawendi, M. G. Munn, L. L. Fukuruma, D. Duda, D. G. Dunst, J. Jain, R. K. TI Hematopoietic Stem cells are located in Niches normoxic SO STRAHLENTHERAPIE UND ONKOLOGIE LA German DT Meeting Abstract CT 17th Annual Meeting of the German-Society-for-Radiation-Oncology CY JUN 02-05, 2011 CL Wiesbaden, GERMANY SP German Soc Radiat Oncol C1 [Niemeyer, E.; Dunst, J.] Med Univ Lubeck, Klin Strahlentherapie, D-23538 Lubeck, Germany. [Niemeyer, E.; Kamoun, W. S.; Gillissen, M.; Martin, J.; Lanning, R.; Munn, L. L.; Fukuruma, D.; Duda, D. G.; Jain, R. K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Niemeyer, E.; Kamoun, W. S.; Gillissen, M.; Martin, J.; Lanning, R.; Munn, L. L.; Fukuruma, D.; Duda, D. G.; Jain, R. K.] Harvard Univ, Sch Med, Boston, MA USA. [Han, H. -S; Bawendi, M. G.] MIT, Dept Chem, Cambridge, MA 02139 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 1 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD JUN PY 2011 VL 187 SU 1 BP 128 EP 128 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 772LU UT WOS:000291236200365 ER PT J AU Basham, C Denneson, LM Millet, L Shen, X Duckart, J Dobscha, SK AF Basham, Chandra Denneson, Lauren M. Millet, Lisa Shen, Xun Duckart, Jonathan Dobscha, Steven K. TI Characteristics and VA Health Care Utilization of U.S. Veterans Who Completed Suicide in Oregon Between 2000 and 2005 SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID DEATH REPORTING SYSTEM; MENTAL-HEALTH; PHYSICAL ILLNESS; FIREARM SUICIDE; MARITAL-STATUS; DEPRESSION; AFFAIRS; VALIDITY; PREDICTORS; PREVENTION AB Oregon Violent Death Reporting System data were linked with Veterans Affairs (VA) administrative data to identify and describe veterans who completed suicide in Oregon from 2000 to 2005 (n = 968), and to describe their VA health care utilization in the year prior to death. Twenty-two percent had received health care in the VA system. Of these, 57% did not have mental health diagnoses and 58% had not seen mental health professionals. A larger proportion of those who accessed care were VA-enrolled and received service-connected disability benefits. Fifty-five veterans were hospitalized during the year prior to death. Of these, 33% completed suicide within 30 days of a hospitalization. Further development of suicide prevention strategies for veterans in the community, including general medical treatment settings, is indicated. C1 [Denneson, Lauren M.; Duckart, Jonathan; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, Portland, OR 97207 USA. [Basham, Chandra] ZoomCare PC, Hillsboro, OR USA. [Denneson, Lauren M.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Millet, Lisa; Shen, Xun] Oregon Publ Hlth Div, Portland, OR USA. RP Denneson, LM (reprint author), Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, POB 1034 P3DEP PC, Portland, OR 97207 USA. EM lauren.denneson@va.gov NR 33 TC 9 Z9 9 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD JUN PY 2011 VL 41 IS 3 BP 287 EP 296 DI 10.1111/j.1943-278X.2011.00028.x PG 10 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 774OG UT WOS:000291395300004 PM 21463353 ER PT J AU Bahn, RS Burch, HB Cooper, DS Garber, JR Greenlee, MC Klein, I Laurberg, P McDougall, IR Montori, VM Rivkees, SA Ross, DS Sosa, JA Stan, MN AF Bahn, Rebecca S. Burch, Henry B. Cooper, David S. Garber, Jeffrey R. Greenlee, M. Carol Klein, Irwin Laurberg, Peter McDougall, I. Ross Montori, Victor M. Rivkees, Scott A. Ross, Douglas S. Sosa, Julie Ann Stan, Marius N. TI Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists SO THYROID LA English DT Article ID ENDOGENOUS SUBCLINICAL HYPERTHYROIDISM; ANTINEUTROPHIL CYTOPLASMIC ANTIBODY; AMIODARONE-INDUCED THYROTOXICOSIS; PERCUTANEOUS ETHANOL INJECTION; HUMAN CHORIONIC-GONADOTROPIN; DRUG-INDUCED AGRANULOCYTOSIS; RADIOACTIVE IODINE THERAPY; MULTINODULAR TOXIC GOITER; QUALITY-OF-LIFE; PARATHYROID-HORMONE ASSAY AB Background: Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition. Methods: The development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Results: Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis. Conclusions: One hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice. C1 [Bahn, Rebecca S.; Montori, Victor M.; Stan, Marius N.] Mayo Clin, Div Endocrinol Metab & Nutr, Rochester, MN 55905 USA. [Burch, Henry B.] Walter Reed Army Med Ctr, Div Endocrinol & Metab, Washington, DC 20307 USA. [Cooper, David S.] Johns Hopkins Univ, Sch Med, Div Endocrinol, Baltimore, MD USA. [Garber, Jeffrey R.] Harvard Vanguard Med Associates, Div Endocrine, Boston, MA USA. [Greenlee, M. Carol] Western Slope Endocrinol, Grand Junction, CO USA. [Klein, Irwin] N Shore Univ Hosp, Thyroid Unit, Manhasset, NY USA. [Laurberg, Peter] Aarhus Univ Hosp, Dept Endocrinol, Aalborg, Denmark. [McDougall, I. Ross] Stanford Univ, Sch Med, Dept Radiol, Div Nucl Med, Stanford, CA 94305 USA. [McDougall, I. Ross] Stanford Univ, Dept Med, Sch Med, Div Endocrinol, Stanford, CA 94305 USA. [Rivkees, Scott A.] Yale Pediat Thyroid Ctr, Dept Pediat, New Haven, CT USA. [Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sosa, Julie Ann] Yale Univ, Sch Med, Div Endocrine Surg, New Haven, CT USA. [Sosa, Julie Ann] Yale Univ, Sch Med, Div Surg Oncol, New Haven, CT USA. RP Bahn, RS (reprint author), Mayo Clin, Div Endocrinol Metab & Nutr, 200 1st St SW, Rochester, MN 55905 USA. EM bahn.rebecca@mayo.edu OI Stan, Marius/0000-0002-1408-8125; Montori, Victor/0000-0003-0595-2898 FU Genzyme FX D.R. is a consultant for Abbott Laboratories and has received research grant support from Genzyme. For all other authors, no competing financial interests exist. NR 358 TC 151 Z9 170 U1 3 U2 32 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JUN PY 2011 VL 21 IS 6 BP 593 EP 646 DI 10.1089/thy.2010.0417 PG 54 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 775LM UT WOS:000291461000005 PM 21510801 ER PT J AU De, S AF De, Subhajyoti TI Somatic mosaicism in healthy human tissues SO TRENDS IN GENETICS LA English DT Review ID COPY-NUMBER-VARIATION; MITOCHONDRIAL-DNA MUTATIONS; L1 RETROTRANSPOSITION; CELL COMPETITION; CHROMOSOMAL MOSAICISM; MONOZYGOTIC TWINS; HUMAN-DISEASE; HUMAN GENOME; HUMAN BRAIN; GENE-EXPRESSION AB From the fertilization of an egg until the death of an individual, somatic cells can accumulate genetic changes, such that cells from different tissues or even within the same tissue differ genetically. The presence of multiple cell clones with distinct genotypes in the same individual is referred to as 'somatic mosaicism'. Many endogenous factors such as mobile elements, DNA polymerase slippage, DNA double-strand break, inefficient DNA repair, unbalanced chromosomal segregation and some exogenous factors such as nicotine and UV exposure can contribute to the generation of somatic mutations, thereby leading to somatic mosaicism. Such changes can potentially affect the epigenetic patterns and levels of gene expression, and ultimately the phenotypes of cells. Although recent studies suggest that somatic mosaicism is widespread during normal development and aging, its implications for heightened disease risks are incompletely understood. Here, I discuss the origins, prevalence and implications of somatic mosaicism in healthy human tissues. C1 [De, Subhajyoti] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [De, Subhajyoti] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP De, S (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. EM subho@jimmy.harvard.edu FU Human Frontier Science Program FX SD thanks Franziska Michor, Elizabeth Murchison, Frank McCaughan and the anonymous reviewers for insightful discussions and critical comments. SD is a recipient of Human Frontier Science Program Long-term Fellowship and also a Fellow at King's College, Cambridge, UK. NR 90 TC 55 Z9 59 U1 0 U2 10 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUN PY 2011 VL 27 IS 6 BP 217 EP 223 DI 10.1016/j.tig.2011.03.002 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 776VS UT WOS:000291567400002 PM 21496937 ER PT J AU Saeidi, N Sander, EA Zareian, R Ruberti, JW AF Saeidi, Nima Sander, Edward A. Zareian, Ramin Ruberti, Jeffrey W. TI Production of highly aligned collagen lamellae by combining shear force and thin film confinement SO ACTA BIOMATERIALIA LA English DT Article DE Collagen; Corneal tissue engineering; Extracellular matrix; Shear stress; Spin coating ID CORNEAL STROMA; ROTATING-DISK; LIQUID-FILMS; CONTACT GUIDANCE; IN-VITRO; X-RAY; FLOW; DYNAMICS; STABILITY; TISSUE AB Load-bearing tissues owe their mechanical strength to their highly anisotropic collagenous structure. To date attempts to engineer mechanically strong connective tissue have failed, mainly due to a lack of ability to reproduce the native collagen organization in constructs synthesized by cultured cells in vitro. The ability to influence the orientation of self-assembling collagen molecules to produce highly anisotropic structures has applications ranging from de novo engineering of complex tissues to the production of organized scaffolds for cell culture contact guidance. In this investigation we have used the simple technique of spin-coating to produce highly aligned arrays of collagen fibrils. By a simple modification of the method we have also successfully produced orthogonal collagen lamellae. Alternating collagen lamellae are frequently seen in load-bearing tissues such as cornea, annulus fibrosus, and cortical bone. Culturing of corneal fibroblasts on aligned collagen shows that the cells adopt the organization of fibrils. In this investigation we observed the reversal of fibrillar growth direction or "hook" formation similar to that seen previously in a microfluidic shear flow chamber. Although the results of this investigation clearly show that it is possible to produce small areas (1 cm(2)) of collagen fibrils with enough alignment to guide fibroblasts, there is evidence that thin film instabilities are likely to be a significant barrier to producing organized collagen fibrils over larger areas. Successful application of this method to produce highly controlled and organized collagenous structures will require the development of techniques to control thin film instability and will be the subject of future work. (C) 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Zareian, Ramin; Ruberti, Jeffrey W.] Northeastern Univ, Dept Mech & Ind Engn, Boston, MA 02115 USA. [Saeidi, Nima] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Sander, Edward A.] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN 55455 USA. RP Ruberti, JW (reprint author), Northeastern Univ, Dept Mech & Ind Engn, Boston, MA 02115 USA. EM j.ruberti@neu.edu FU NEI NIH HHS [R01 EY015500-05, R01 EY015500-01A1S1, R01 EY015500-03, R01 EY015500-06, R01 EY015500-01A1, R01 EY015500-02, R01 EY015500-04, R01 EY015500] NR 51 TC 8 Z9 8 U1 4 U2 35 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 J9 ACTA BIOMATER JI Acta Biomater. PD JUN PY 2011 VL 7 IS 6 BP 2437 EP 2447 DI 10.1016/j.actbio.2011.02.038 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 771SU UT WOS:000291181800009 PM 21362500 ER PT J AU Goldfarb, I Panda, B Wylie, B Riley, L AF Goldfarb, Ilona Panda, Britta Wylie, Blair Riley, Laura TI Uptake of influenza vaccine in pregnant women during the 2009 H1N1 influenza pandemic SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE H1N1; influenza; pregnancy; vaccination ID IMMUNIZATION; ATTITUDES AB The goals of this study were to define the uptake of H1N1 and seasonal influenza vaccination during pregnancy among women delivering during the 2009 H1N1 pandemic and explore barriers to vaccination. All postpartum women at the Massachusetts General Hospital from January 2010 through March 2010 were invited to complete an anonymous questionnaire about demographics, vaccination status, and attitudes about vaccination during pregnancy. Among 370 participants (53% response rate), 81% accepted both the H1N1 and seasonal influenza vaccines during pregnancy. Patients who declined one or both vaccines cited concerns over safety as a major deterrent. Of the 36% of participants who reported having flu-like symptoms during this pregnancy only 8.6% took oseltamivir. While a high vaccination rate was identified in this study, further education is needed to reassure patients regarding vaccine safety. Education for providers and patients emphasizing the benefits of early treatment of pregnant women with flu-like symptoms should be a priority. C1 [Goldfarb, Ilona; Panda, Britta; Wylie, Blair; Riley, Laura] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol, Boston, MA USA. RP Goldfarb, I (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM igoldfarb@partners.org FU Centers for Disease Control and Prevention; Association of Maternal and Child Health Programs FX Publication of this article was supported by the Centers for Disease Control and Prevention and the Association of Maternal and Child Health Programs. NR 23 TC 40 Z9 40 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 2011 VL 204 IS 6 SU 1 BP S112 EP S115 DI 10.1016/j.ajog.2011.01.007 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 772AF UT WOS:000291201100019 PM 21345408 ER PT J AU Surman, CBH Biederman, J Spencer, T Yorks, D Miller, CA Petty, CR Faraone, SV AF Surman, Craig B. H. Biederman, Joseph Spencer, Thomas Yorks, Dayna Miller, Carolyn A. Petty, Carter R. Faraone, Stephen V. TI Deficient Emotional Self-Regulation and Adult Attention Deficit Hyperactivity Disorder: A Family Risk Analysis SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PEDIATRIC BIPOLAR DISORDER; SUBTHRESHOLD DIAGNOSES; LATE-ONSET; DEFICIT/HYPERACTIVITY DISORDER; ADHD ADULTS; TRAITS AB Objective: A growing body of research suggests that deficient emotional self-regulation (DESR) is prevalent and morbid among patients with attention deficit hyperactivity disorder (ADHD). Family studies provide a method of clarifying the co-occurrence of clinical features, but no family studies have yet addressed ADHD and DESR. Method: Participants were 83 probands with and without ADHD and 128 siblings. All were assessed for axis I DSM-IV conditions with structured diagnostic interviews. The authors defined DESR in adult probands and siblings using items from the Barkley Current Behavior Scale. Analyses tested hypotheses about the familial relationship between ADHD and DESR. Results: Siblings of ADHD probands were at elevated risk of having ADHD, irrespective of the presence or absence of DESR in the proband. The risk for DESR was elevated in siblings of ADHD plus DESR probands but not in siblings of ADHD probands. ADHD and DESR cosegregated in siblings. The risk for other psychiatric disorders was similar in siblings of the ADHD proband groups. Conclusions: The pattern of inheritance of ADHD with DESR preliminarily suggests that DESR may be a familial subtype of ADHD. Our data suggest that DESR is not an expression of other axis I DSM-IV disorders or of nonfamilial environmental factors. The authors cannot exclude contribution of non-axis-I DSM-IV disorders to risk for DESR and cannot determine whether the cosegregation of ADHD in DESR within families is a result of genes or familial environmental risk factors. Further investigation of DESR and its correlates and treatment both in and outside the context of ADHD is warranted. C1 [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Neurosci, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY 13210 USA. Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Unit, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Neurosci, Syracuse, NY 13210 USA. EM sfaraone@childpsychresearch.org OI Faraone, Stephen/0000-0002-9217-3982 FU Abbott; Alza; Cephalon; Eli Lilly; Hilda; Preston Davis Foundation; McNeil; Merck; National Institutes of Health [R01MH-57934]; New River; Organon; Pfizer; Shire; Takeda; Janssen-Ortho; Novartis; Elminda; Janssen; Fundacion Areces; Medice Pharmaceuticals; Spanish Child Psychiatry Association; AstraZeneca; Bristol-Myers Squibb; Celltech; Esai; Forest; GlaxoSmithKline; Gliatech; NARSAD; National Institute of Child Health and Human Development; National Institute on Drug Abuse; National Institute of Mental Health; Neurosearch; Noven; Otsuka; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma; Wyeth; Shire Pharmaceuticals FX Dr. Surman has received research support from Abbott, Alza, Cephalon, Eli Lilly, the Hilda and Preston Davis Foundation, McNeil, Merck, the National Institutes of Health, New River, Organon, Pfizer, Shire, and Takeda; he has been sponsored by Janssen-Ortho, McNeil, Novartis, and Shire for speaking and educational activities and has been a consultant/advisor to McNeil, Shire, and Takeda; and he has received honoraria from Reed Medical Education ( a logistics collaborator for the Massachusetts General Hospital Psychiatry Academy [commercial entities supporting the Massachusetts General Hospital Psychiatry Academy are listed on the Academy's website, http://www.mghcme.org]). Dr. Biederman is currently receiving research support from Elminda, Janssen, McNeil, and Shire; in 2010, he received a speaker's fee from Fundacion Dr. Manuel Camelo A. C. and honoraria from the Massachusetts General Hospital Psychiatry Academy for a tuition-funded CME course; in 2009, he received speaker's fees from Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association; in previous years, he received research support, consultation fees, or speaker's fees from Abbott, Alza, AstraZeneca, Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly, Esai, Forest, GlaxoSmithKline, Gliatech, Janssen, McNeil, Merck, NARSAD, the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the National Institute of Mental Health, Neurosearch, New River, Novartis, Noven, Organon, Otsuka, Pfizer, Pharmacia, the Prechter Foundation, Shire, the Stanley Foundation, UCB Pharma, and Wyeth. Dr. Spencer has received research support from, has served as a speaker or on a speaker's bureau for, or has been an advisor or served on an advisory board for Cephalon, Eli Lilly, Glaxo-SmithKline, Janssen, McNeil, the National Institutes of Mental Health, Novartis, Pfizer, and Shire. In the past year, Dr. Faraone has received consulting fees from and served on advisory boards for Shire Development in addition to receiving research support from the National Institutes of Health and Shire; in previous years, he received consulting fees from or served on advisory boards of or participated in continuing medical education programs sponsored by Eli Lilly, Janssen, McNeil, Novartis, Pfizer, and Shire; he has also received research support from Eli Lilly, the National Institutes of Health, Pfizer, and Shire; and he receives royalties from a book published by Guilford Press. Ms. Yorks, Ms. Miller, and Mr. Petty report no financial relationships with commercial interests.; Supported in part by National Institutes of Health grant R01MH-57934 (Dr. Faraone) and a grant from Shire Pharmaceuticals. NR 24 TC 42 Z9 42 U1 2 U2 10 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2011 VL 168 IS 6 BP 617 EP 623 DI 10.1176/appi.ajp.2010.10081172 PG 7 WC Psychiatry SC Psychiatry GA 772OJ UT WOS:000291242900010 PM 21498464 ER PT J AU Andreola, G Chittenden, M Shaffer, J Cosimi, AB Kawai, T Cotter, P LoCascio, SA Morokata, T Dey, BR Tolkoff-Rubin, NT Preffer, F Bonnefoix, T Kattleman, K Spitzer, TR Sachs, DH Sykes, M AF Andreola, G. Chittenden, M. Shaffer, J. Cosimi, A. B. Kawai, T. Cotter, P. LoCascio, S. A. Morokata, T. Dey, B. R. Tolkoff-Rubin, N. T. Preffer, F. Bonnefoix, T. Kattleman, K. Spitzer, T. R. Sachs, D. H. Sykes, M. TI Mechanisms of Donor-Specific Tolerance in Recipients of Haploidentical Combined Bone Marrow/Kidney Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Bone marrow transplantation; kidney transplantation; mixed chimerism; tolerance ID REGULATORY T-CELLS; ANTIGEN-SPECIFIC HYPOREACTIVITY; MARROW-TRANSPLANTATION; MIXED CHIMERISM; MAINTENANCE IMMUNOSUPPRESSION; HOMEOSTATIC PROLIFERATION; IMMUNE RECONSTITUTION; ALLOGRAFT TOLERANCE; THYMOCYTE GLOBULIN; GRAFT-REJECTION AB We recently reported long-term organ allograft survival without ongoing immunosuppression in four of five patients receiving combined kidney and bone marrow transplantation from haploidentical donors following nonmyeloablative conditioning. In vitro assays up to 18 months revealed donor-specific unresponsiveness. We now demonstrate that T cell recovery is gradual and is characterized by memory-type cell predominance and an increased proportion of CD4+CD25+CD127-FOXP3+ Treg during the lymphopenic period. Complete donor-specific unresponsiveness in proliferative and cytotoxic assays, and in limiting dilution analyses of IL-2-producing and cytotoxic cells, developed and persisted for the 3-year follow-up in all patients, and extended to donor renal tubular epithelial cells. Assays in two of four patients were consistent with a role for a suppressive tolerance mechanism at 6 months to 1 year, but later (>= 18 months) studies on all four patients provided no evidence for a suppressive mechanism. Our studies demonstrate, for the first time, long-term, systemic donor-specific unresponsiveness in patients with HLA-mismatched allograft tolerance. While regulatory cells may play an early role, long-term tolerance appears to be maintained by a deletion or anergy mechanism. C1 [Andreola, G.; Chittenden, M.; Shaffer, J.; Cotter, P.; LoCascio, S. A.; Morokata, T.; Kattleman, K.; Sachs, D. H.; Sykes, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. [Cosimi, A. B.; Kawai, T.; Tolkoff-Rubin, N. T.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Transplant Unit, Boston, MA 02115 USA. [Dey, B. R.; Spitzer, T. R.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Bone Marrow Transplant Uni, Boston, MA USA. [Preffer, F.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Bonnefoix, T.] Inst Albert Bonniot, INSERM, U823, Grenoble 9, France. [Bonnefoix, T.] CHU Grenoble, Plateforme Hosp Genet Mol Tumeurs, Pole Rech & Pole Biol, Grenoble 9, France. [Sykes, M.] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY USA. [Bonnefoix, T.] CHU Grenoble, Plateforme Hosp Genet Mol Tumeurs, Cellular & Mol Haematol Unit, Grenoble 9, France. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. EM megan.sykes@columbia.edu FU NIH [R01AI084074, ITN N01AI15416]; Multiple Myeloma Research Foundation; American Society of Transplantation and Umberto Veronesi Foundation FX American Recovery and Reinvestment Act funding NIH R01AI084074, NIH ITN N01AI15416, Multiple Myeloma Research Foundation.; G.A. was supported by the American Society of Transplantation and Umberto Veronesi Foundation. Author contributions: G.A. wrote the manuscript, performed flow cytometry and in vitro assays, analyzed data and prepared specimens. M.C., J.S. and P.C. coordinated sample acquisition, prepared specimens, performed in vitro assays. S.A.L. and T.M. performed in vitro assays and assisted with data analysis. F.I.P. provided expert advice on and performed flow cytometry. K.K. supervised and coordinated research sample acquisition. T.B. aided in the analysis and interpretation of limiting dilution assays. A. B.C. T.K., B.R.D., N.T.R., T.S. and D.H.S. designed, supervised and carried out the clinical protocol and patient care. M.S. participated in the design of the clinical protocol, cowrote the paper and participated in and oversaw design of all laboratory studies, data analysis and interpretation, and preparation of the manuscript. NR 44 TC 50 Z9 52 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2011 VL 11 IS 6 BP 1236 EP 1247 DI 10.1111/j.1600-6143.2011.03566.x PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 772ZV UT WOS:000291277700020 PM 21645255 ER PT J AU Dutta, P Dart, M Roenneburg, DA Torrealba, JR Burlingham, WJ AF Dutta, P. Dart, M. Roenneburg, D. A. Torrealba, J. R. Burlingham, W. J. TI Pretransplant Immune-Regulation Predicts Allograft Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE NIMA; regulatory T cells; transplantation tolerance ID NONINHERITED MATERNAL ANTIGENS; CELLS; IMMUNOSUPPRESSION; TRANSPLANTATION; MECHANISM; SURVIVAL; HUMANS; FETAL; MICE AB CD4+ Tregs specific for noninherited maternal antigens (NIMAd) are detectable in some but not all B6 x BDF(1) backcross, H-2b homozygous offspring, and their presence is strongly correlated with extent of maternal (BDF(1)) microchimerism. We hypothesized that the level of pretransplant donor antigen-specific Tregs could predict allograft tolerance. To test this idea, mice were screened for bystander suppression in a DTH assay, followed 1 week later by DBA/2 heterotopic heart transplantation. NIMAd-exposed, H-2b offspring that failed to suppress DTH uniformly rejected heart allografts (12/12) by d15. In contrast, 5/6 NIMAd-exposed DTH 'regulators' accepted their allografts > 100 days. The defect in 'nonregulator" offspring could be corrected by transfer of CD4+CD25+, but not CD4+CD25neg or CD8+T cells from transplant acceptor mice. In conclusion, donor-specific T reg screening of F1 backcross offspring correctly predicted which recipients would accept a heart allograft. If translated to the clinic, similar pretransplant Treg screening could greatly enhance the effectiveness of tolerance as a clinical strategy in transplantation between family members. C1 [Dutta, P.; Dart, M.; Roenneburg, D. A.; Burlingham, W. J.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Dutta, P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Cambridge, MA 02138 USA. [Torrealba, J. R.] Univ Wisconsin, Dept Pathol, Madison, WI 53706 USA. RP Burlingham, WJ (reprint author), Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM burlingham@surgery.wisc.edu FU NIH [5R01AI066219-05, R01 AI066229] FX We would like to thank Steve Schumacher for technical assistance in typing mice, DNA extraction and qPCR. P.D. designed experiments, and performed all experiments (except DTH assay) and heterotopic heart transplantation, analyzed data and prepared manuscript. M.D. performed DTH assay and manuscript editing. D.A.R. and J.R.T. helped with immunohistochemistry. W.J.B. was responsible for overall experimental design and manuscript editing. This work was supported by 5R01AI066219-05 from the NIH (to W.J.B.).; The research was supported by National Institute of Health Grant R01 AI066229. NR 18 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2011 VL 11 IS 6 BP 1296 EP 1301 DI 10.1111/j.1600-6143.2011.03484.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 772ZV UT WOS:000291277700026 PM 21449933 ER PT J AU Chan, JA Blaszkowsky, LS Enzinger, PC Ryan, DP Abrams, TA Zhu, AX Temel, JS Schrag, D Bhargava, P Meyerhardt, JA Wolpin, BM Fidias, P Zheng, H Florio, S Regan, E Fuchs, CS AF Chan, J. A. Blaszkowsky, L. S. Enzinger, P. C. Ryan, D. P. Abrams, T. A. Zhu, A. X. Temel, J. S. Schrag, D. Bhargava, P. Meyerhardt, J. A. Wolpin, B. M. Fidias, P. Zheng, H. Florio, S. Regan, E. Fuchs, C. S. TI A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma SO ANNALS OF ONCOLOGY LA English DT Article DE cetuximab; esophageal adenocarcinoma; gastric adenocarcinoma ID GROWTH-FACTOR RECEPTOR; ADVANCED ESOPHAGOGASTRIC CANCER; METASTATIC COLORECTAL-CANCER; GASTROESOPHAGEAL JUNCTION; CLINICAL-RESPONSE; LUNG-CANCER; COMBINATION; GEFITINIB; PLUS; CISPLATIN AB Background: Epidermal growth factor receptor (EGFR) is overexpressed in a significant proportion of esophageal and gastric carcinomas. Although previous studies have examined tyrosine kinase inhibitors of EGFR, there remains limited data regarding the role of EGFR-directed monoclonal antibody therapy in these malignancies. We carried out a multi-institutional phase II study of cetuximab, a monoclonal antibody against EGFR, in patients with unresectable or metastatic esophageal or gastric adenocarcinoma. Patients and Methods: Thirty-five patients with previously treated metastatic esophageal or gastric adenocarcinoma were treated with weekly cetuximab, at an initial dose of 400 mg/m(2) followed by weekly infusions at 250 mg/m(2). Patients were followed for toxicity, treatment response, and survival. Results: Treatment with cetuximab was well tolerated; no patients were taken off study due to drug-related adverse events. One (3%) partial treatment response was noted. Two (6%) patients had stable disease after 2 months of treatment. Median progression-free survival and overall survival were 1.6 and 3.1 months, respectively. Conclusion: Although well tolerated, cetuximab administered as a single agent had minimal clinical activity in patients with metastatic esophageal and gastric adenocarcinoma. Ongoing studies of EGFR inhibitors in combination with other agents may define a role for these agents in the treatment of esophageal and gastric cancer. C1 [Chan, J. A.; Enzinger, P. C.; Abrams, T. A.; Schrag, D.; Bhargava, P.; Meyerhardt, J. A.; Wolpin, B. M.; Florio, S.; Regan, E.; Fuchs, C. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, J. A.; Enzinger, P. C.; Abrams, T. A.; Schrag, D.; Bhargava, P.; Meyerhardt, J. A.; Wolpin, B. M.; Fuchs, C. S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Chan, J. A.; Blaszkowsky, L. S.; Enzinger, P. C.; Ryan, D. P.; Abrams, T. A.; Zhu, A. X.; Temel, J. S.; Schrag, D.; Bhargava, P.; Meyerhardt, J. A.; Wolpin, B. M.; Fidias, P.; Zheng, H.; Fuchs, C. S.] Harvard Univ, Sch Med, Dept Hematol Oncol, Boston, MA USA. [Blaszkowsky, L. S.; Ryan, D. P.; Zhu, A. X.; Temel, J. S.; Fidias, P.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Zheng, H.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Chan, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jang@partners.org FU Bristol-Myers Squibb FX Bristol-Myers Squibb provided cetuximab and clinical trial funding support. NR 35 TC 59 Z9 61 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 IS 6 BP 1367 EP 1373 DI 10.1093/annonc/mdq604 PG 7 WC Oncology SC Oncology GA 770BA UT WOS:000291060800018 PM 21217058 ER PT J AU Jonker, DJ Rosen, LS Sawyer, MB de Braud, F Wilding, G Sweeney, CJ Jayson, GC McArthur, GA Rustin, G Goss, G Kantor, J Velasquez, L Syed, S Mokliatchouk, O Feltquate, DM Kollia, G Nuyten, DSA Galbraith, S AF Jonker, D. J. Rosen, L. S. Sawyer, M. B. de Braud, F. Wilding, G. Sweeney, C. J. Jayson, G. C. McArthur, G. A. Rustin, G. Goss, G. Kantor, J. Velasquez, L. Syed, S. Mokliatchouk, O. Feltquate, D. M. Kollia, G. Nuyten, D. S. A. Galbraith, S. TI A phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors SO ANNALS OF ONCOLOGY LA English DT Article DE antiangiogenesis; brivanib; fibroblast growth factor; vascular endothelial growth ID RENAL-CELL CARCINOMA; ADVANCED HEPATOCELLULAR-CARCINOMA; GROWTH-FACTOR RECEPTOR; COLORECTAL-CANCER; TYROSINE KINASES; SORAFENIB; BEVACIZUMAB; THERAPY; PTK787/ZK-222584; ANGIOGENESIS AB Background: This study was designed to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of brivanib in patients with advanced/metastatic solid tumors. Patients and methods: Ninety patients enrolled in this two-part, phase I open-label study of oral brivanib alaninate. The primary objectives of this study were (in part A) dose-limiting toxicity, maximum tolerated dose (MTD) and the lowest biologically active dose level and (in part B) the optimal dose/dose range. The secondary objectives of this study were preliminary evidence of antitumor activity, PK and PD. Results: Across part A (open-label dose escalation and MTD) and part B (open-label dose optimization), 68 patients received brivanib alaninate. Brivanib demonstrated a manageable toxicity profile at doses of 180-800 mg. Most toxic effects were mild. Systemic exposure of the active moiety brivanib increased linearly <= 1000 mg/day. The MTD was 800 mg/day. Forty-four patients were treated at the MTD: 20 with 800 mg continuously, 11 with 800 mg intermittently and 13 with 400 mg b.i.d. doses. Partial responses were confirmed in two patients receiving brivanib 600 mg. Dynamic contrast-enhanced magnetic resonance imaging demonstrated statistically significant decreases in parameters reflecting tumor vascularity and permeability after multiple doses in the 800-mg continuous q.d. and 400-mg b.i.d. dose cohorts. Conclusion: In patients with advanced/metastatic cancer, brivanib demonstrates promising antiangiogenic and antitumor activity and manageable toxicity at doses <= 800 mg orally q.d., the recommended phase II study dose. C1 [Jonker, D. J.; Goss, G.] Univ Ottawa, Ottawa Hosp Canc Ctr, Div Med Oncol, Ottawa, ON K1H 8L6, Canada. [Rosen, L. S.] Premiere Oncol, Dept Oncol, Santa Monica, CA USA. [Sawyer, M. B.] Cross Canc Inst, Dept Oncol, Edmonton, AB T6G 1Z2, Canada. [de Braud, F.] European Inst Oncol, Dept Med, Div Clin Pharmacol & New Drugs, Milan, Italy. [Wilding, G.] Univ Wisconsin Carbone Canc Ctr, Dept Oncol, Madison, WI USA. [Sweeney, C. J.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Jayson, G. C.] Univ Manchester, Dept Oncol, Christie Hosp, Manchester, Lancs, England. [McArthur, G. A.] Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Australia. [Rustin, G.] Mt Vernon Canc Ctr, Dept Med Oncol, Northwood, Middx, England. [Kantor, J.; Velasquez, L.; Syed, S.; Mokliatchouk, O.; Feltquate, D. M.; Kollia, G.; Nuyten, D. S. A.; Galbraith, S.] Bristol Myers Squibb Co, Res & Dev, Princeton, NJ USA. RP Jonker, DJ (reprint author), Univ Ottawa, Ottawa Hosp Canc Ctr, Div Med Oncol, 501 Smyth Rd,Box 912, Ottawa, ON K1H 8L6, Canada. EM djonker@ottawahospital.on.ca RI Jayson, Gordon/O-8224-2015; de Braud, Filippo/B-9997-2017 OI Jayson, Gordon/0000-0002-8515-8944; de Braud, Filippo/0000-0003-0103-730X FU Bristol-Myers Squibb [CA182002] FX This work was supported by research funding from Bristol-Myers Squibb (Study No. CA182002). This trial is registered at www.clinicaltrials.gov as NCT00207051. NR 31 TC 46 Z9 49 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 IS 6 BP 1413 EP 1419 DI 10.1093/annonc/mdq599 PG 7 WC Oncology SC Oncology GA 770BA UT WOS:000291060800023 PM 21131369 ER PT J AU Albasanz-Puig, A Murray, J Preusch, M Coan, D Namekata, M Patel, Y Dong, ZM Rosenfeld, ME Wijelath, ES AF Albasanz-Puig, Adaia Murray, Jacqueline Preusch, Michael Coan, Daniel Namekata, Mayumi Patel, Yatin Dong, Zhao Ming Rosenfeld, Michael E. Wijelath, Errol S. TI Oncostatin M is expressed in atherosclerotic lesions: A role for Oncostatin M in the pathogenesis of atherosclerosis SO ATHEROSCLEROSIS LA English DT Article DE Oncostatin M; Smooth muscle cell; Atherosclerosis; Carotid plaques; ApoE(-/-); STAT-1; STAT-3 ID SMOOTH-MUSCLE-CELLS; IN-VITRO; ENDOTHELIAL-CELLS; SIGNALING PATHWAY; CAROTID PLAQUE; ED-B; ANGIOGENESIS; INDUCTION; CYTOKINES; DISEASE AB Objective: Chronic inflammation plays a pivotal role in the development and progression of atherosclerosis. The inflammatory response is mediated by cytokines. The aim of this study was to determine if OncostatinM(OSM), a monocyte and T-lymphocyte specific cytokine is present in atherosclerotic lesions. We also investigated the roles of signal transducer and activator of transcription (STAT)-1 and STAT-3 in regulating OSM-induced smooth muscle cell (SMC) proliferation, migration and cellular fibronectin (cFN) synthesis. Methods and results: Immunostaining of atherosclerotic lesions from human carotid plaques demonstrated the expression of OSM antigen in both macrophages and SMCs. Explanted SMCs from human carotid plaques expressed OSM mRNA and protein as determined by RT-PCR and Western blotting. Using the chow-fed ApoE-/- mouse model of atherosclerosis, we observed that OSM was initially expressed in the intima at 20 weeks of age. By 30 weeks, OSM was expressed in both the intima and media. In vitro studies show that OSM promotes SMC proliferation, migration and cFN synthesis. Lentivirus mediated-inhibition of STAT-1 and STAT-3 prevented OSM-induced SMC proliferation, migration and cellular fibronectin synthesis. Conclusions: These findings demonstrate that OSM is expressed in atherosclerotic lesions and may contribute to the progression of atherosclerosis by promoting SMC proliferation, migration and extracellular matrix protein synthesis through the STAT pathway. Published by Elsevier Ireland Ltd. C1 [Preusch, Michael; Dong, Zhao Ming; Rosenfeld, Michael E.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Albasanz-Puig, Adaia; Murray, Jacqueline; Coan, Daniel; Namekata, Mayumi; Dong, Zhao Ming; Wijelath, Errol S.] VA Puget Sound Hlth Care Syst, Dept Surg, Div Vasc Surg, Seattle, WA USA. [Patel, Yatin] Kings Coll London, Sch Med London, Div Cardiovasc, Dept Cardiol, London, England. RP Wijelath, ES (reprint author), Dept Vet Affairs Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM errolw@u.washington.edu FU U.S. Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory FX This study was supported by the U.S. Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research Program. We thank Dr. Michael Sobel for providing carotid endarterectomy specimens and for critical review of the manuscript. NR 40 TC 18 Z9 20 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JUN PY 2011 VL 216 IS 2 BP 292 EP 298 DI 10.1016/j.atherosclerosis.2011.02.003 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 773XA UT WOS:000291343600009 PM 21376322 ER PT J AU Haspel, J Shaik, RS Ifedigbo, E Nakahira, K Dolinay, T Englert, JA Choi, AMK AF Haspel, Jeffrey Shaik, Rahamthulla S. Ifedigbo, Emeka Nakahira, Kiichi Dolinay, Tamas Englert, Joshua A. Choi, Augustine M. K. TI Characterization of macroautophagic flux in vivo using a leupeptin-based assay SO AUTOPHAGY LA English DT Article DE macroautophagy; autophagy; flux; mice; in vivo; LC3; GABARAP; GATE-16; leupeptin; cycloheximide ID ISOLATED RAT HEPATOCYTES; AUTOPHAGIC DEGRADATION; MORPHOMETRIC-ANALYSIS; MAMMALIAN AUTOPHAGY; ELECTRON-MICROSCOPY; CELL BIOLOGY; MOUSE-LIVER; TNF-ALPHA; LC3; PROTEIN AB Macroautophagy is a highly conserved catabolic process that is crucial for organ homeostasis in mammals. However, methods to directly measure macroautophagic activity (or flux) in vivo are limited. In this study we developed a quantitative macroautophagic flux assay based on measuring LC3b protein turnover in vivo after administering the protease inhibitor leupeptin. Using this assay we then characterized basal macroautophagic flux in different mouse organs. We found that the rate of LC3b accumulation after leupeptin treatment was greatest in the liver and lowest in spleen. Interestingly we found that LC3a, an ATG8/LC3b homologue and the LC3b-interacting protein p62 were degraded with similar kinetics to LC3b. However, the LC3b-related proteins GABARAP and GATE-16 were not rapidly turned over in mouse liver, implying that different LC3b homologues may contribute to macroautophagy via distinct mechanisms. Nutrient starvation augmented macroautophagic flux as measured by our assay, while refeeding the animals after a period of starvation significantly suppressed flux. We also confirmed that beclin 1 heterozygous mice had reduced basal macroautophagic flux compared to wild-type littermates. These results illustrate the usefulness of our leupeptin-based assay for studying the dynamics of macroautophagy in mice. C1 [Haspel, Jeffrey; Shaik, Rahamthulla S.; Ifedigbo, Emeka; Nakahira, Kiichi; Englert, Joshua A.; Choi, Augustine M. K.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Haspel, Jeffrey] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA USA. [Dolinay, Tamas] Univ Tennessee, Coll Med, Dept Med, Chattanooga, TN USA. [Choi, Augustine M. K.] Kyung Hee Univ, Coll Med, Seoul, South Korea. RP Choi, AMK (reprint author), Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. EM amchoi@rics.bwh.harvard.edu FU NIH [T32 HL007633, R03HL097005]; FAMRI FX We thank Beth Levine for the generous gift of beclin 1 heterozygous mice and Tamotsu Yoshimori for his GST-LC3b expression construct. We also thank Louise Trakimas for her technical assistance with electron microscopy and Stefan Ryter and Robyn Haspel for their critique of this manuscript. This work was funded by NIH T32 HL007633, NIH R03HL097005 and a FAMRI Clinical Innovator Award. NR 75 TC 44 Z9 45 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JUN PY 2011 VL 7 IS 6 BP 629 EP 642 DI 10.4161/auto.7.6.15100 PG 14 WC Cell Biology SC Cell Biology GA 771JP UT WOS:000291153300007 PM 21460622 ER PT J AU Pike, LS Smift, AL Croteau, NJ Ferrick, DA Wu, M AF Pike, Lisa S. Smift, Amy L. Croteau, Nicole J. Ferrick, David A. Wu, Min TI Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article DE Fatty acid oxidation; NADPH; ROS; Oxidative stress; Mitochondrial dysfunction ID NADP(+)-DEPENDENT ISOCITRATE DEHYDROGENASE; CANCER-CELLS; GLUTAMINE-METABOLISM; AEROBIC GLYCOLYSIS; TRANSFORMED-CELLS; HYDROGEN-PEROXIDE; TUMOR-CELLS; STRESS; APOPTOSIS; BIOLOGY AB Normal differentiated cells rely primarily on mitochondrial oxidative phosphorylation to produce adenosine triphosphate (ATP) to maintain their viability and functions by using three major bioenergetic fuels: glucose, glutamine and fatty acids. Many cancer cells, however, rely on aerobic glycolysis for their growth and survival, and recent studies indicate that some cancer cells depend on glutamine as well. This altered metabolism in cancers occurs through oncogene activation or loss of tumor suppressor genes in multiple signaling pathways, including the phosphoinositide 3-kinase and Myc pathways. Relatively little is known, however, about the role of fatty acids as a bioenergetic fuel in growth and survival of cancer cells. Here, we report that human glioblastoma SF188 cells oxidize fatty acids and that inhibition of fatty acid beta-oxidation by etomoxir, a carnitine palmitoyltransferase 1 inhibitor, markedly reduces cellular ATP levels and viability. We also found that inhibition of fatty acid oxidation decreases nicotinamide adenine dinucleotide phosphate (NADPH) levels and the reduced glutathione (GSH) content and elevates intracellular reactive oxygen species. These results suggest that modulation of fatty acid oxidation controls the NADPH level. In the presence of reactive oxygen species scavenger tiron, however, ATP depletion is prevented without restoring fatty acid oxidation. This suggests that oxidative stress may lead to bioenergetic failure and cell death. Our work provides evidence that mitochondrial fatty acid oxidation may provide NADPH for defense against oxidative stress and prevent ATP loss and cell death. This article is part of a Special Issue entitled: Bioenergetics of Cancer. (C) 2010 Elsevier B.V. All rights reserved. C1 [Pike, Lisa S.; Smift, Amy L.; Ferrick, David A.; Wu, Min] Seahotse Biosci, N Billerica, MA 01862 USA. [Croteau, Nicole J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Wu, M (reprint author), Seahotse Biosci, N Billerica, MA 01862 USA. EM mwu@seahorsebio.com NR 34 TC 105 Z9 107 U1 1 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD JUN PY 2011 VL 1807 IS 6 SI SI BP 726 EP 734 DI 10.1016/j.bbabio.2010.10.022 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 772MH UT WOS:000291237500022 PM 21692241 ER PT J AU Armand, P Kim, HT Rhodes, J Sainvil, MM Cutler, C Ho, VT Koreth, J Alyea, EP Hearsey, D Neufeld, EJ Fleming, MD Steen, H Anderson, D Kwong, RY Soiffer, R Antin, JH AF Armand, Philippe Kim, Haesook T. Rhodes, Joanna Sainvil, Marie-Michele Cutler, Corey Ho, Vincent T. Koreth, John Alyea, Edwin P. Hearsey, Doreen Neufeld, Ellis J. Fleming, Mark D. Steen, Hanno Anderson, Damon Kwong, Raymond Y. Soiffer, Robert. Antin, Joseph H. TI Iron Overload in Patients with Acute Leukemia or MDS Undergoing Myeloablative Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Iron overload; Acute myeloid leukemia; Acute lymphoblastic leukemia; Myelodysplastic syndromes; Stem cell transplantation ID PRETRANSPLANTATION SERUM FERRITIN; RISK-FACTOR; MYELODYSPLASTIC SYNDROME; PROGNOSTIC IMPACT; CHELATING THERAPY; MEASUREMENT-ERROR; THALASSEMIA; LIVER; QUANTIFICATION; MALIGNANCIES AB Patients with hematologic malignancies undergoing allogeneic stem cell transplantation (HSCT) commonly have an elevated serum ferritin prior to HSCT, which has been associated with increased mortality after transplantation. This has led to the suggestion that iron overload is common and deleterious in this patient population. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. We report a prospective study of 48 patients with acute leukemia (AL) or myelodysplastic syndromes (MDS) undergoing myeloablative HSCT, using magnetic resonance imaging (MRI) to estimate liver iron content (LIC) and cardiac iron. The median (and range) pre-HSCT value of serum ferritin was 1549 ng/mL (20-6989); serum hepcidin, 59 ng/mL (10-468); labile plasma iron, 0 LPI units (0.0-0.9). Eighty-five percent of patients had hepatic iron overload (HIO), and 42% had significant HIO (LIC >= 5.0 mg/gdw). Only I patient had cardiac iron overload. There was a strong correlation between pre-HSCT serum ferritin and estimated LIC (r = .75), which was mostly dependent on prior transfusion history. Serum hepcidin was appropriately elevated in patients with HIO. Labile plasma iron elevation was rare. A regression calibration analysis supported the hypothesis that elevated pre-HSCT LIC is significantly associated with inferior post-HSCT survival. These results contribute to our understanding of the prevalence, mechanism, and consequences of iron overload in HSCT. Biol Blood Marrow Transplant 17: 852-860 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [Armand, Philippe; Sainvil, Marie-Michele; Cutler, Corey; Ho, Vincent T.; Koreth, John; Alyea, Edwin P.; Hearsey, Doreen; Soiffer, Robert.; Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Rhodes, Joanna] SUNY Stony Brook, Dept Med, Sch Med, Stony Brook, NY 11794 USA. [Neufeld, Ellis J.] Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Fleming, Mark D.; Steen, Hanno; Anderson, Damon] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Cardiovasc Med, Boston, MA 02115 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM parmand@partners.org RI Neufeld, Ellis/F-9331-2011 FU Novartis Oncology; Jock and Bunny Adams Research and Education Endowment; National Institutes of Health [CA142106-06]; Leukemia and Lymphoma Society FX This work was funded in part by grants from Novartis Oncology, the Jock and Bunny Adams Research and Education Endowment, and the National Institutes of Health, CA142106-06. P.A. is a recipient of a Special Fellowship in Clinical Research from the Leukemia and Lymphoma Society. NR 30 TC 38 Z9 42 U1 0 U2 7 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 JUN PY 2011 VL 17 IS 6 BP 852 EP 860 DI 10.1016/j.bbmt.2010.09.006 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 771XM UT WOS:000291194000008 PM 20854920 ER PT J AU Declercq, E Young, R Cabral, H Ecker, J AF Declercq, Eugene Young, Robin Cabral, Howard Ecker, Jeffrey TI Is a Rising Cesarean Delivery Rate Inevitable? Trends in Industrialized Countries, 1987 to 2007 SO BIRTH-ISSUES IN PERINATAL CARE LA English DT Article DE cesarean delivery rates; cesarean trends; cross-national analysis; trend analysis ID PELVIC FLOOR; SECTION; RISKS AB Background: Cesarean delivery rates have been rising rapidly in many countries in the last decade. The objective of this research is to examine cesarean rates in industrialized countries and assess patterns in the trends toward increasing rates. Methods: We examined cesarean delivery rates per 1,000 live births from 1987 to 2007 in 22 industrialized countries. To enhance comparability, the inclusion criteria were at least 50,000 births annually and a per capita gross domestic product of at least U.S.$10,000 in 2007. Poisson regression was selected to model the cesarean delivery rates of countries across time. Results: We examined overall cesarean delivery rates, absolute changes in these rates, and changes in trend lines for cesarean rates for the period from 1987 to 2007. In 2007, 11 of the 21 countries reported overall cesarean rates of more than 25 percent, led by Italy (39%), Portugal (35%), the United States (32%), and Switzerland (32%). Five countries, the Slovak Republic, Czech Republic, Ireland, Austria, and Hungary more than doubled their cesarean delivery rate between 1992 and 2007. Comparing changes in rates across time periods, 14 countries experienced a greater increase in rates in the period between 1998 and 2002 compared with the period between 1993 and 1997. Comparing trends from 2003-2007 to 1998-2002, eighteen countries experienced a slowing down of rate increases across these two periods. Conclusion: Although cesarean delivery rates continue to rise, the rate of increase appears to be slowing down in most industrialized countries. (BIRTH 38:2 June 2011). C1 [Declercq, Eugene] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA 02118 USA. [Young, Robin] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Young, Robin] Harvard Univ, Sch Med, Brigham & Womens Hosp, Osteoarthritis & Arthrit Ctr Outcomes Res,Dept Or, Cambridge, MA 02138 USA. [Ecker, Jeffrey] Massachusetts Gen Hosp, Maternal Fetal Med Residency Program, Boston, MA 02114 USA. RP Declercq, E (reprint author), Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, 801 Massachusetts Ave,CT-4, Boston, MA 02118 USA. OI Declercq, Eugene/0000-0001-5411-3033; Cabral, Howard/0000-0002-1185-8331 NR 30 TC 64 Z9 70 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-7659 J9 BIRTH-ISS PERINAT C JI Birth-Issue Perinat. Care PD JUN PY 2011 VL 38 IS 2 BP 99 EP 104 DI 10.1111/j.1523-536X.2010.00459.x PG 6 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 766SW UT WOS:000290807800002 PM 21599731 ER PT J AU Mawardi, H Elad, S Correa, ME Stevenson, K Woo, SB Almazrooa, S Haddad, R Antin, JH Soiffer, R Treister, N AF Mawardi, H. Elad, S. Correa, M. E. Stevenson, K. Woo, S-B Almazrooa, S. Haddad, R. Antin, J. H. Soiffer, R. Treister, N. TI Oral epithelial dysplasia and squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation: clinical presentation and treatment outcomes SO BONE MARROW TRANSPLANTATION LA English DT Article DE hematopoietic; oral epithelial dysplasia; squamous cell carcinoma; allogeneic; transplantation ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; CHILDHOOD ACUTE-LEUKEMIA; SEVERE APLASTIC-ANEMIA; SECONDARY MALIGNANCIES; RISK-FACTORS; FANCONI-ANEMIA; SOLID CANCERS; TOPICAL APPLICATION; GENOMIC ALTERATIONS AB Late complications of allogeneic hematopoietic stem cell transplantation (HSCT) include a risk of secondary malignancies. Optimization for early diagnosis and treatment of oral premalignant or malignant lesions requires an assessment of potential predisposing risk factors. The medical records of patients who developed oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) following allogeneic-HSCT were reviewed. Data on HSCT course, chronic graft-versus-host disease (cGVHD), and clinical outcome were recorded; landmark survival was calculated. Twenty-six patients with OED (n = 8) and OSCC (n = 18) were identified with a median follow-up of 26.5 and 21.5 months, respectively. Premalignant and malignant oral lesions were diagnosed at a median time of 2.5 and 8 years after HSCT, respectively. Chronic GVHD was present in 96% of patients and of these, 96% had oral involvement. Multifocal oral cancer was found in 28% of cases, and localized recurrence was observed in 44% of cases. These results suggest that oral cGVHD may be considered a potential risk factor for the development of OSCC following allogeneic-HSCT. The observation that oral cancers were frequently multifocal and recurred locally suggests that these cancers may be more aggressive. Vigilant follow-up and coordination of care are critical. Bone Marrow Transplantation (2011) 46, 884-891; doi: 10.1038/bmt.2011.77; published online 4 April 2011 C1 [Mawardi, H.; Woo, S-B; Almazrooa, S.; Treister, N.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Elad, S.] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dept Oral Biol, IL-91010 Jerusalem, Israel. [Correa, M. E.] Univ Estadual Campinas, Dent Ambulatory Hematol & Blood Transfus Ctr, Sao Paulo, Brazil. [Stevenson, K.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Mawardi, H.; Woo, S-B; Treister, N.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Haddad, R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Antin, J. H.; Soiffer, R.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Mawardi, H.; Almazrooa, S.] King Abdulaziz Univ, Fac Dent, Dept Oral Med, Jeddah 21413, Saudi Arabia. RP Mawardi, H (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 75 Francis St, Boston, MA 02115 USA. EM hmawardi@partners.org RI Sangue, Inct/I-1919-2013; Pizzigatti Correa, Maria Elvira/J-4389-2012 OI Pizzigatti Correa, Maria Elvira/0000-0001-5714-4089 FU NIH [CA142106] FX The oral medicine specialists (HM, SE, MEC, S-BW and NT) thank the Hematopoietic Cell Transplantation and Head and Neck Oncology departments at their respective institutions for their daily collaboration in the management of these patients. We also extend our gratitude to our patients and their families. Supported in part by NIH Grant CA142106. NR 61 TC 19 Z9 20 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 2011 VL 46 IS 6 BP 884 EP 891 DI 10.1038/bmt.2011.77 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 774KC UT WOS:000291383100018 PM 21460866 ER PT J AU Drzezga, A Becker, JA Van Dijk, KRA Sreenivasan, A Talukdar, T Sullivan, C Schultz, AP Sepulcre, J Putcha, D Greve, D Johnson, KA Sperling, RA AF Drzezga, Alexander Becker, J. Alex Van Dijk, Koene R. A. Sreenivasan, Aishwarya Talukdar, Tanveer Sullivan, Caroline Schultz, Aaron P. Sepulcre, Jorge Putcha, Deepti Greve, Doug Johnson, Keith A. Sperling, Reisa A. TI Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden SO BRAIN LA English DT Article DE amyloid; cortical hubs; functional connectivity; metabolism; mild cognitive impairment; positron emission tomography; magnetic resonance imaging ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; RESTING-STATE NETWORKS; PITTSBURGH COMPOUND-B; ALZHEIMERS-DISEASE; FUNCTIONAL CONNECTIVITY; FDG-PET; HUMAN BRAIN; AEROBIC GLYCOLYSIS; COMPONENT ANALYSIS AB Disruption of functional connectivity between brain regions may represent an early functional consequence of beta-amyloid pathology prior to clinical Alzheimer's disease. We aimed to investigate if non-demented older individuals with increased amyloid burden demonstrate disruptions of functional whole-brain connectivity in cortical hubs (brain regions typically highly connected to multiple other brain areas) and if these disruptions are associated with neuronal dysfunction as measured with fluorodeoxyglucose-positron emission tomography. In healthy subjects without cognitive symptoms and patients with mild cognitive impairment, we used positron emission tomography to assess amyloid burden and cerebral glucose metabolism, structural magnetic resonance imaging to quantify atrophy and novel resting state functional magnetic resonance imaging processing methods to calculate whole-brain connectivity. Significant disruptions of whole-brain connectivity were found in amyloid-positive patients with mild cognitive impairment in typical cortical hubs (posterior cingulate cortex/precuneus), strongly overlapping with regional hypometabolism. Subtle connectivity disruptions and hypometabolism were already present in amyloid-positive asymptomatic subjects. Voxel-based morphometry measures indicate that these findings were not solely a consequence of regional atrophy. Whole-brain connectivity values and metabolism showed a positive correlation with each other and a negative correlation with amyloid burden. These results indicate that disruption of functional connectivity and hypometabolism may represent early functional consequences of emerging molecular Alzheimer's disease pathology, evolving prior to clinical onset of dementia. The spatial overlap between hypometabolism and disruption of connectivity in cortical hubs points to a particular susceptibility of these regions to early Alzheimer's-type neurodegeneration and may reflect a link between synaptic dysfunction and functional disconnection. C1 [Drzezga, Alexander; Becker, J. Alex; Van Dijk, Koene R. A.; Talukdar, Tanveer; Sepulcre, Jorge; Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Drzezga, Alexander; Becker, J. Alex; Van Dijk, Koene R. A.; Talukdar, Tanveer; Sepulcre, Jorge; Johnson, Keith A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Drzezga, Alexander; Van Dijk, Koene R. A.; Sreenivasan, Aishwarya; Talukdar, Tanveer; Sullivan, Caroline; Schultz, Aaron P.; Sepulcre, Jorge; Putcha, Deepti; Greve, Doug] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sullivan, Caroline; Schultz, Aaron P.; Putcha, Deepti; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment,Dept Neurol, Boston, MA 02115 USA. [Van Dijk, Koene R. A.; Sepulcre, Jorge] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Van Dijk, Koene R. A.; Sepulcre, Jorge] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Sreenivasan, Aishwarya; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Drzezga, A (reprint author), Tech Univ Munich, Dept Nucl Med, Klinikum Rechts Isar, Ismaningerstr 22, D-81675 Munich, Germany. EM a.drzezga@lrz.tum.de FU German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) [DR 445/3-1, 4-1]; National Institute on Aging [R01AG027435]; Alzheimer's Disease Research Center (ADRC) [P50AG005134, P01 AG036694]; Anonymous Medical Foundation; Alzheimer's Association FX Funding for this study has been provided by: The German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) (DR 445/3-1, 4-1 to A.D.), the National Institute on Aging (R01AG027435 to R.A.S. and K.A.J.), the Alzheimer's Disease Research Center (ADRC) (P50AG005134 to R.A.S. and K.A.J., P01 AG036694 to R.A.S.), an Anonymous Medical Foundation (to R.A.S. and K.A.J.) and the Alzheimer's Association (to R.A.S.). NR 61 TC 146 Z9 148 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 2011 VL 134 BP 1635 EP 1646 DI 10.1093/brain/awr066 PN 6 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 770CF UT WOS:000291063900007 PM 21490054 ER PT J AU Thliveris, AT Clipson, L White, A Waggoner, J Plesh, L Skinner, BL Zahm, CD Sullivan, R Dove, WF Newton, MA Halberg, RB AF Thliveris, Andrew T. Clipson, Linda White, Alanna Waggoner, Jesse Plesh, Lauren Skinner, Bridget L. Zahm, Christopher D. Sullivan, Ruth Dove, William F. Newton, Michael A. Halberg, Richard B. TI Clonal Structure of Carcinogen-Induced Intestinal Tumors in Mice SO CANCER PREVENTION RESEARCH LA English DT Article ID CHIMERIC MICE; APC MUTATIONS; ORIGIN; ADENOMAS; TUMORIGENESIS; MULTIPLICITY; RESISTANCE; PLA2G2A; DNA AB Previous studies have shown that intestinal tumors from Apc(Min/+) (Min) mice and familial adenomatous polyposis (FAP) patients are often polyclonal. We sought to determine whether polyclonality is unique to tumors arising from hereditary predispositions or, instead, is a common feature of intestinal tumorigenesis in other pathways to tumorigenesis. Ethylnitrosourea-induced intestinal tumors from mice wild type at the Apc locus and chimeric for the Rosa26 lineage marker were analyzed. Many were overtly polyclonal, being composed of a mixture of Rosa26(+) and Rosa26(-) neoplastic cells. Statistical analyses revealed that polyclonality could be explained by interactions between two initiated clones separated by a very short distance. The frequency of overtly polyclonal tumors and the range of interactions estimated in this model are similar to those observed when analyzing familial tumors from Min mice. Thus, polyclonality does not depend on the familial pathway to tumorigenesis. Interactions between two initiated clones might provide a selective advantage during the early stages of intestinal tumorigenesis. Cancer Prev Res; 4(6); 916-23. (C) 2011 AACR. C1 [Thliveris, Andrew T.] Univ Wisconsin Madison, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Clipson, Linda; White, Alanna; Waggoner, Jesse; Dove, William F.] Univ Wisconsin Madison, Dept Oncol, Madison, WI USA. [Newton, Michael A.] Univ Wisconsin Madison, Dept Stat, Madison, WI USA. [Newton, Michael A.] Univ Wisconsin Madison, Dept Biostat & Med Informat, Madison, WI USA. [Plesh, Lauren; Skinner, Bridget L.; Zahm, Christopher D.; Halberg, Richard B.] Univ Wisconsin Madison, Div Gastroenterol & Hepatol, Dept Med, Madison, WI USA. [Sullivan, Ruth] Univ Wisconsin Madison, Res Anim Resource Ctr, Madison, WI USA. [Dove, William F.] Univ Wisconsin Madison, Genet Lab, Madison, WI USA. [Sullivan, Ruth; Dove, William F.; Newton, Michael A.; Halberg, Richard B.] Univ Wisconsin Madison, UW Carbone Canc Ctr, Madison, WI USA. [Thliveris, Andrew T.] William S Middleton Mem Vet Adm Med Ctr, Surg Serv, Madison, WI USA. RP Halberg, RB (reprint author), K4 532 Clin Sci Ctr, MC 5124,600 Highland Ave, Madison, WI 53792 USA. EM rbhalberg@medicine.wisc.edu OI Zahm, Christopher/0000-0002-2117-7003 FU National Cancer Institute [R01 CA123438, R37 CA63677, P30 CA014520]; UW Division of Gastroenterology and Hepatology; UW Department of Medicine; UW School of Medicine and Public Health FX The study was supported by National Cancer Institute grants R01 CA123438 (R.B. Halberg), R37 CA63677 (W.F. Dove), P30 CA014520 (UW Carbone Cancer Center Core Grant), and start-up funds to RBH from the UW Division of Gastroenterology and Hepatology, the UW Department of Medicine, and the UW School of Medicine and Public Health. NR 24 TC 6 Z9 6 U1 0 U2 5 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 JUN PY 2011 VL 4 IS 6 BP 916 EP 923 DI 10.1158/1940-6207.CAPR-11-0022 PG 8 WC Oncology SC Oncology GA 771ZR UT WOS:000291199700017 PM 21636550 ER PT J AU Kim, H Catana, C Ratai, EM Andronesi, OC Jennings, DL Batchelor, TT Jain, RK Sorensen, AG AF Kim, Heisoog Catana, Ciprian Ratai, Eva-Maria Andronesi, Ovidiu C. Jennings, Dominique L. Batchelor, Tracy T. Jain, Rakesh K. Sorensen, A. Gregory TI Serial Magnetic Resonance Spectroscopy Reveals a Direct Metabolic Effect of Cediranib in Glioblastoma SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PROTON MR SPECTROSCOPY; HUMAN BRAIN-TUMORS; IN-VIVO; ANTIANGIOGENIC THERAPY; H-1-NMR SPECTROSCOPY; KINASE INHIBITOR; GLIAL TUMORS; ANGIOGENESIS; RADIATION AB Proton magnetic resonance spectroscopy is increasingly used in clinical studies of brain tumor to provide information about tissue metabolic profiles. In this study, we evaluated changes in the levels of metabolites predominant in recurrent glioblastoma multiforme (rGBM) to characterize the response of rGBM to antiangiogenic therapy. We examined 31 rGBM patients treated with daily doses of cediranib, acquiring serial chemical shift imaging data at specific time points during the treatment regimen. We defined spectra from three regions of interest (ROI)-enhancing tumor (ET), peritumoral tissue, and normal tissue on the contralateral side (cNT)-in post-contrast T1-weighted images, and normalized the concentrations of N-acetylaspartate (NAA) and choline (Cho) in each ROI to the concentration of creatine in cNT (norCre). We analyzed the ratios of these normalized metabolites (i.e., NAA/Cho, NAA/norCre, and Cho/norCre) by averaging all patients and categorizing two different survival groups. Relative to pretreatment values, NAA/Cho in ET was unchanged through day 28. However, after day 28, NAA/Cho significantly increased in relation to a significant increase in NAA/norCre and a decrease in Cho/norCre; interestingly, the observed trend was reversed after day 56, consistent with the clinical course of GBM recurrence. Notably, receiver operating characteristic analysis indicated that NAA/Cho in tumor shows a high prediction to 6-month overall survival. These metabolic changes in these rGBM patients strongly suggest a direct metabolic effect of cediranib and might also reflect an antitumor response to antiangiogenic treatment during the first 2 months of treatment. Further study is needed to confirm these findings. Cancer Res; 71(11); 3745-52. (C)2011 AACR. C1 [Kim, Heisoog; Catana, Ciprian; Ratai, Eva-Maria; Andronesi, Ovidiu C.; Jennings, Dominique L.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Kim, Heisoog] MIT, Dept Nucl Sci & Engn Hlth Sci & Technol, Cambridge, MA 02139 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Kim, H (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. EM heisoog@nmr.mgh.harvard.edu FU NIH [R21, K24]; Harvard Catalyst FX The work was financially supported by NIH grants R21 and K24, and by the Harvard Catalyst grant. NR 51 TC 25 Z9 25 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2011 VL 71 IS 11 BP 3745 EP 3752 DI 10.1158/0008-5472.CAN-10-2991 PG 8 WC Oncology SC Oncology GA 771JR UT WOS:000291153500003 PM 21507932 ER PT J AU Simpson, DR Yu, M Zheng, SY Zhao, ZM Muthuswamy, SK Tansey, WP AF Simpson, David R. Yu, Min Zheng, Siyuan Zhao, Zhongming Muthuswamy, Senthil K. Tansey, William P. TI Epithelial Cell Organization Suppresses Myc Function by Attenuating Myc Expression SO CANCER RESEARCH LA English DT Article ID C-MYC; BREAST-CANCER; ESSENTIAL COFACTOR; LUMEN FORMATION; IN-VIVO; POLARITY; PROTEIN; ACINI; PHOSPHORYLATION; OVEREXPRESSION AB c-Myc is an oncogene transcription factor that causes cancer in many settings, including solid tumors that arise in the context of organized tissue structures. Given that disruption of tissue architecture frequently occurs in cancer, there is considerable interest in how cell organization impacts oncogene function. A previous report found that organization of mammary epithelial cells into defined 3-dimensional structures renders them insensitive to the effects of retrovirus-mediated overexpression of Myc, leading to the notion that organization tempers the sensitivity of individual cells to Myc activity. In this article, we report that epithelial cell organization does not profoundly alter Myc activity but, instead, suppresses Myc by modulating its expression. We show that the morphogenesis of mammary epithelial cells into organized acinar structures in vitro is accompanied by widespread changes in gene expression patterns, including a substantial decrease in the expression of Myc. Concomitant with the decrease in endogenous Myc expression, we observe a decrease in transcription from retroviral vectors during morphogenesis and find that Myc transgene expression in acini is much lower than in unorganized cells. This decrease in Myc transgene activity is responsible for the apparent recalcitrance of organized cells to ectopic Myc, as adenovirus-mediated expression of Myc in organized structures potently induces apoptosis. These observations reveal that organization does not alter the inherent response of epithelial cells to Myc and suggest that other tumor suppression mechanisms, apart from structure, antagonize Myc in the development of solid tumors. Cancer Res; 71(11); 3822-30. (C) 2011 AACR. C1 [Simpson, David R.; Tansey, William P.] Vanderbilt Univ, Dept Cell & Dev Biol, Sch Med, Nashville, TN 37232 USA. [Zheng, Siyuan; Zhao, Zhongming] Vanderbilt Univ, Dept Biomed Informat, Sch Med, Nashville, TN 37232 USA. [Simpson, David R.] Watson Sch Biol Sci, Cold Spring Harbor, NY USA. [Simpson, David R.; Yu, Min; Muthuswamy, Senthil K.; Tansey, William P.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Yu, Min] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Yu, Min] Harvard Univ, Sch Med, Charlestown, MA USA. [Muthuswamy, Senthil K.] Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Toronto, ON, Canada. RP Tansey, WP (reprint author), Vanderbilt Univ, Dept Cell & Dev Biol, Sch Med, 465 21st Ave S, Nashville, TN 37232 USA. EM william.p.tansey@vanderbilt.edu FU Department of Defense [W81XWH-06-1-0731, BC075024]; Vanderbilt Ingram Cancer Center [CA68465]; Cold Spring Harbor Laboratory Cancer Center [CA45508]; U.S. Public Health Service [CA098830, CA13106] FX This study was supported by Department of Defense Traineeship Award W81XWH-06-1-0731 (D.R. Simpson), Vanderbilt Ingram Cancer Center support grant CA68465 (Z. Zhao and W.P. Tansey), Cold Spring Harbor Laboratory Cancer Center support grant CA45508 (S.K. Muthuswamy and W.P. Tansey), and Department of Defense grant BC075024 (S.K. Muthuswamy). U.S. Public Health Service grants CA098830 (S.K. Muthuswamy) and CA13106 (W.P. Tansey). NR 35 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2011 VL 71 IS 11 BP 3822 EP 3830 DI 10.1158/0008-5472.CAN-10-3782 PG 9 WC Oncology SC Oncology GA 771JR UT WOS:000291153500011 PM 21610111 ER PT J AU Permuth-Wey, J Kim, D Tsai, YY Lin, HY Chen, YA Barnholtz-Sloan, J Birrer, MJ Bloom, G Chanock, SJ Chen, ZH Cramer, DW Cunningham, JM Dagne, G Ebbert-Syfrett, J Fenstermacher, D Fridley, BL Garcia-Closas, M Gayther, SA Ge, W Gentry-Maharaj, A Gonzalez-Bosquet, J Goode, EL Iversen, E Jim, H Kong, W McLaughlin, J Menon, U Monteiro, ANA Narod, SA Pharoah, PDP Phelan, CM Qu, XT Ramus, SJ Risch, H Schildkraut, JM Song, HL Stockwell, H Sutphen, R Terry, KL Tyrer, J Vierkant, RA Wentzensen, N Lancaster, JM Cheng, JQ Sellers, TA AF Permuth-Wey, Jennifer Kim, Donghwa Tsai, Ya-Yu Lin, Hui-Yi Chen, Y. Ann Barnholtz-Sloan, Jill Birrer, Michael J. Bloom, Gregory Chanock, Stephen J. Chen, Zhihua Cramer, Daniel W. Cunningham, Julie M. Dagne, Getachew Ebbert-Syfrett, Judith Fenstermacher, David Fridley, Brooke L. Garcia-Closas, Montserrat Gayther, Simon A. Ge, William Gentry-Maharaj, Aleksandra Gonzalez-Bosquet, Jesus Goode, Ellen L. Iversen, Edwin Jim, Heather Kong, William McLaughlin, John Menon, Usha Monteiro, Alvaro N. A. Narod, Steven A. Pharoah, Paul D. P. Phelan, Catherine M. Qu, Xiaotao Ramus, Susan J. Risch, Harvey Schildkraut, Joellen M. Song, Honglin Stockwell, Heather Sutphen, Rebecca Terry, Kathryn L. Tyrer, Jonathan Vierkant, Robert A. Wentzensen, Nicolas Lancaster, Johnathan M. Cheng, Jin Q. Sellers, Thomas A. CA OCAC TI LIN28B Polymorphisms Influence Susceptibility to Epithelial Ovarian Cancer SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; MICRORNA-RELATED GENES; RISK; LOCI; CARCINOMA; VARIANTS; PATHWAYS; IDENTIFICATION; TRANSFORMATION; METAANALYSIS AB Defective microRNA (miRNA) biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNP) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P < 0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G>A), an SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR = 0.90, 95% CI: 0.82-0.98; P = 0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B overexpression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be because of reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility. Cancer Res; 71(11); 3896-903. (C) 2011 AACR. C1 [Permuth-Wey, Jennifer; Tsai, Ya-Yu; Phelan, Catherine M.; Sellers, Thomas A.] Univ S Florida, H Lee Moffitt Canc Ctr, Canc Epidemiol Program, Div Populat Sci, Tampa, FL 33682 USA. [Kim, Donghwa; Kong, William; Cheng, Jin Q.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Interdisciplinary Oncol, Tampa, FL 33682 USA. [Lin, Hui-Yi; Chen, Y. Ann] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Biostat, Tampa, FL 33682 USA. [Bloom, Gregory; Chen, Zhihua; Fenstermacher, David; Ge, William; Qu, Xiaotao] Univ S Florida, H Lee Moffitt Canc Ctr, Dept iomed Informat, Tampa, FL 33682 USA. [Ebbert-Syfrett, Judith; Gonzalez-Bosquet, Jesus; Lancaster, Johnathan M.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Womens Oncol, Tampa, FL 33682 USA. [Jim, Heather] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Hlth Outcomes & Behav, Tampa, FL 33682 USA. [Permuth-Wey, Jennifer; Dagne, Getachew; Stockwell, Heather] Univ S Florida, Dept Epidemiol & Biostat, Coll Publ Hlth, Tampa, FL 33682 USA. [Sutphen, Rebecca] Univ S Florida, Pediat Epidemiol Ctr, Coll Med, Tampa, FL 33682 USA. Case Sch Med, Case Comprehens Canc Ctr, Cleveland, OH USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barnholtz-Sloan, Jill; Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Epidemiol Ctr, Boston, MA 02115 USA. [Chanock, Stephen J.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Cunningham, Julie M.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Fridley, Brooke L.; Goode, Ellen L.; Vierkant, Robert A.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Garcia-Closas, Montserrat] UCL, EGA Inst Womens Hlth, Inst Canc Res, Sect Epidemiol, London, England. [Garcia-Closas, Montserrat] UCL, EGA Inst Womens Hlth, Inst Canc Res, Sect Genet, London, England. [Garcia-Closas, Montserrat] UCL, EGA Inst Womens Hlth, Breakthrough Breast Canc Res Ctr, London, England. [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, EGA Inst Womens Hlth, Dept Gynecol Oncol, London, England. [Gayther, Simon A.; Ramus, Susan J.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Iversen, Edwin] Duke Univ, Dept Stat Sci, Durham, NC USA. [Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [McLaughlin, John] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Narod, Steven A.] Ctr Res Womens Hlth, Toronto, ON, Canada. [Pharoah, Paul D. P.; Song, Honglin; Tyrer, Jonathan] Univ Cambridge, Dept Oncol, Cambridge, England. [Risch, Harvey] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Sellers, TA (reprint author), MRC CANCONT, Moffitt Res Inst, Dept Epidemiol & Genet, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM thomas.sellers@moffitt.org RI McLaughlin, John/E-4577-2013; Fridley, Brooke/D-8315-2015; Garcia-Closas, Montserrat /F-3871-2015; OI Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat /0000-0003-1033-2650; Monteiro, Alvaro/0000-0002-8448-4801; Vierkant, Robert/0000-0001-6242-5221; Ramus, Susan/0000-0003-0005-7798 FU Moffitt Cancer Center/University of South Florida; Cancer Center [P30-CA0762-92]; Mayo Foundation; American Cancer Society [CRTG-00-196-01-CCE]; Advanced Cancer Detection Center, Department of Defense [DAMD-17-98-1-8659]; Canadian Cancer Society; NIH [R01-CA-63682, R01-CA-63678]; National Cancer Institute [P30-CA-15083]; NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics; Center for Cancer Research; Cancer Research U.K.; Eve Appeal; OAK Foundation; Department of Health's NIHR Biomedical Research Centre; [R01-CA-114343]; [R01-CA114343-S1]; [R01-CA-122443]; [P50-CA-136393]; [R01-CA-76016]; [R01-CA-106414]; [CA-54419]; [P50 CA105009] FX The genotyping, bioinformatic, and biostatistical data analysis for stage 1 was supported by R01-CA-114343 and R01-CA114343-S1 and the Moffitt Cancer Center/University of South Florida Anna Valentine Fund and Cancer Center Support Grant P30-CA0762-92. The MAY study is supported by R01-CA-122443 and P50-CA-136393 and funding from the Mayo Foundation. The NCO study is supported by R01-CA-76016. The TBO study is supported by R01-CA-106414, the American Cancer Society (CRTG-00-196-01-CCE), and the Advanced Cancer Detection Center Grant, Department of Defense (DAMD-17-98-1-8659). The TOR study is supported by grants from the Canadian Cancer Society and the NIH (R01-CA-63682 and R01-CA-63678). The Mayo Clinic Genotyping Shared Resource is supported by the National Cancer Institute (P30-CA-15083).; Of studies that participated in stage 2, the NEC study is supported by grants CA-54419 and P50 CA105009. The POL study was supported by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the Center for Cancer Research. The SEA study is funded by a program grant from Cancer Research U.K. The UKO study is supported by funding from Cancer Research U.K., the Eve Appeal, and the OAK Foundation. Some of this work was undertaken at UCLH/UCL, who received some funding from the Department of Health's NIHR Biomedical Research Centre funding scheme. U.K. genotyping and data analysis was supported by a project grant from Cancer Research U.K. U.K. studies also make use of data generated by the Wellcome Trust Case-Control consortium. A list of investigators who contributed to the generation of data is available at www.wtccc.org.uk. NR 40 TC 50 Z9 52 U1 0 U2 11 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 JUN 1 PY 2011 VL 71 IS 11 BP 3896 EP 3903 DI 10.1158/0008-5472.CAN-10-4167 PG 8 WC Oncology SC Oncology GA 771JR UT WOS:000291153500019 PM 21482675 ER PT J AU Alam, M Siddiqui, S Lee, VV Elayda, MA Nambi, V Yang, EY Jneid, HM Wilson, JM Ballantyne, CM Virani, SS AF Alam, Mahboob Siddiqui, Sahar Lee, Vei-Vei Elayda, McArthur A. Nambi, Vijay Yang, Eric Y. Jneid, Hani M. Wilson, James M. Ballantyne, Christie M. Virani, Salim S. TI Isolated Coronary Artery Bypass Grafting in Obese Individuals - A Propensity Matched Analysis of Outcomes SO CIRCULATION JOURNAL LA English DT Article DE Coronary artery bypass grafting; Morbidity; Mortality; Obesity; Outcomes ID BODY-MASS INDEX; THORACIC-SURGEONS DATABASE; IN-HOSPITAL MORTALITY; LONG-TERM OUTCOMES; CARDIAC-SURGERY; EXTREME OBESITY; RISK-FACTOR; POSTOPERATIVE MORBIDITY; METABOLIC SYNDROME; HEART-FAILURE AB Background: There is conflicting data regarding the impact of obesity on morbidity and mortality in patients undergoing isolated coronary artery bypass grafting (CABG). Methods and Results: Retrospective cohort analysis of patients who underwent CABG from January 1, 1995, through July 31, 2010 was performed. Patients were classified as obese or non-obese (body mass index >= 30.0 kg/m(2) and <30.0 kg/m(2), respectively). The primary outcome was in-hospital mortality. Secondary outcomes included postoperative respiratory failure, postoperative stroke, postoperative myocardial infarction, sternal and leg wound infections, postoperative atrial fibrillation, postoperative ventricular tachycardia, postoperative renal failure and length of hospital stay. Propensity-matched stepwise multivariable logistic regression was performed. Of 13,115 patients, 4,619 (35.2%) were obese. In the propensity-matched logistic regression models (n=8,442), obesity was not associated with postoperative mortality (odds ratio=1.13, 95% confidence interval 0.86-1.48). However, obesity was associated with postoperative respiratory failure, postoperative renal insufficiency, sternal wound infection, and leg wound infection. Obesity was also associated with a decreased risk of postoperative bleeding and re-operation from bleeding. Conclusions: Obesity was associated with an increased risk of postoperative respiratory failure, postoperative renal failure, and surgical site infections. However, obesity was not associated with in-hospital mortality in patients undergoing CABG. (Circ J 2011; 75: 1378-1385) C1 [Alam, Mahboob; Nambi, Vijay; Jneid, Hani M.; Ballantyne, Christie M.; Virani, Salim S.] Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. [Lee, Vei-Vei; Elayda, McArthur A.; Wilson, James M.; Virani, Salim S.] Baylor Coll Med, Texas Heart Inst, Houston, TX 77030 USA. [Nambi, Vijay; Yang, Eric Y.; Ballantyne, Christie M.; Virani, Salim S.] Baylor Coll Med, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [Jneid, Hani M.; Virani, Salim S.] Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. [Jneid, Hani M.; Virani, Salim S.] Baylor Coll Med, Hlth Policy & Qual Program, Houston, TX 77030 USA. [Siddiqui, Sahar] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. [Siddiqui, Sahar] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Siddiqui, Sahar] Univ Florida, Sch Publ Hlth, Gainesville, FL USA. RP Alam, M (reprint author), Baylor Coll Med, Dept Med, Cardiol Sect, 1709 Dryden Rd,Suite 9-90,BCM 620, Houston, TX 77030 USA. EM malam@bcm.tmc.edu RI Yang, Eric/C-1170-2010; OI Yang, Eric/0000-0003-2234-3269; Virani, Salim/0000-0001-9541-6954 FU St. Luke's Episcopal Hospital; Department of Veterans Affairs Health Services Research and Development Service (Health Service Research Development) [CDA-09-028] FX The authors thank Ms. Joanna A. Brooks, BA, for her editorial assistance. This work was supported by the Muller Fund for Cardiovascular Research at St. Luke's Episcopal Hospital. Dr. Virani is also supported via a Department of Veterans Affairs Health Services Research and Development Service (Health Service Research & Development) Career Development Award (Grant number: CDA-09-028). NR 68 TC 11 Z9 12 U1 0 U2 2 PU JAPANESE CIRCULATION SOC PI KYOTO PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO, 606-8305, JAPAN SN 1346-9843 J9 CIRC J JI Circ. J. PD JUN PY 2011 VL 75 IS 6 BP 1378 EP 1385 DI 10.1253/circj.CJ-10-1129 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 771RH UT WOS:000291177900018 PM 21498907 ER PT J AU Hall, AL Peterson, CL Kautz, SA Neptune, RR AF Hall, A. L. Peterson, C. L. Kautz, S. A. Neptune, R. R. TI Relationships between muscle contributions to walking subtasks and functional walking status in persons with post-stroke hemiparesis SO CLINICAL BIOMECHANICS LA English DT Article DE Forward dynamics simulation; Modeling; Biomechanics; Gait; Muscle function ID MECHANICAL-PROPERTIES; GAIT SPEED; STROKE; SUPPORT; PROGRESSION; WORK; CLASSIFICATION; OPTIMIZATION; FLEXORS; FORCES AB Background: Persons with post-stroke hemiparesis usually walk slowly and asymmetrically. Stroke severity and functional walking status are commonly predicted by post-stroke walking speed. The mechanisms that limit walking speed, and by extension functional walking status, need to be understood to improve post-stroke rehabilitation methods. Methods: Three-dimensional forward dynamics walking simulations of hemiparetic subjects (and speed-matched controls) with different levels of functional walking status were developed to investigate the relationships between muscle contributions to walking subtasks and functional walking status. Muscle contributions to forward propulsion, swing initiation and power generation were analyzed during the pre-swing phase of the gait cycle and compared between groups. Findings: Contributions from the paretic leg muscles (i.e., soleus, gastrocnemius and gluteus medius) to forward propulsion increased with improved functional walking status, with the non-paretic leg muscles (i.e., rectus femoris and vastii) compensating for reduced paretic leg propulsion in the limited community walker. Contributions to swing initiation from both paretic (i.e., gastrocnemius, iliacus and psoas) and non-paretic leg muscles (i.e., hamstrings) also increased as functional walking status improved. Power generation was also an important indicator of functional walking status, with reduced paretic leg power generation limiting the paretic leg contribution to forward propulsion and leg swing initiation. Interpretation: These results suggest that deficits in muscle contributions to the walking subtasks of forward propulsion, swing initiation and power generation are directly related to functional walking status and that improving output in these muscle groups may be an effective rehabilitation strategy for improving post-stroke hemiparetic walking. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Hall, A. L.; Peterson, C. L.; Neptune, R. R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Kautz, S. A.] Malcom Randall VA Med Ctr, Brain Rehabil Res Ctr, Gainesville, FL USA. [Kautz, S. A.] Med Univ S Carolina, Div Phys Therapy, Dept Hlth Sci & Res, Charleston, SC USA. [Kautz, S. A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Neptune, RR (reprint author), Univ Texas Austin, Dept Mech Engn, 1 Univ Stn C2200, Austin, TX 78712 USA. EM rneptune@mail.utexas.edu RI Kinney, Allison/J-5814-2013; Peterson, Carrie/C-6007-2016; OI Kinney, Allison/0000-0003-3553-0733; Peterson, Carrie/0000-0002-7169-2089; Kautz, Steven/0000-0003-3151-8235 FU NIH [RO1 HD46820]; Rehabilitation Research & Development Service of the VA FX The authors would like to thank Erin Carr, Dr. Mark Bowden, Dr. Bhavana Raja, Dr. Cameron Nott, Dr. Chitra Balasubramanian, Kelly Rooney and Ryan Knight for help with the data collection and processing and the members of the Neuromuscular Biomechanics Lab at The University of Texas at Austin for their insightful comments on the manuscript. This work was funded by NIH grant RO1 HD46820 and the Rehabilitation Research & Development Service of the VA. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NICHD or VA. NR 27 TC 32 Z9 32 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD JUN PY 2011 VL 26 IS 5 BP 509 EP 515 DI 10.1016/j.clinbiomech.2010.12.010 PG 7 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 771RN UT WOS:000291178500013 PM 21251738 ER PT J AU Liu, JQ Liao, S Huang, YH Samuel, R Shi, T Naxerova, K Huang, PG Kamoun, W Jain, RK Fukumura, D Xu, L AF Liu, Jieqiong Liao, Shan Huang, Yuhui Samuel, Rekha Shi, Tony Naxerova, Kamila Huang, Peigen Kamoun, Walid Jain, Rakesh K. Fukumura, Dai Xu, Lei TI PDGF-D Improves Drug Delivery and Efficacy via Vascular Normalization, But Promotes Lymphatic Metastasis by Activating CXCR4 in Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-D; HUMAN OVARIAN-CARCINOMA; ANTI-VEGF TREATMENT; RECEPTOR-BETA; DOWN-REGULATION; PROTEIN-KINASE; IN-SITU; EXPRESSION; ANGIOGENESIS; CELLS AB Purpose: Unlike platelet-derived growth factor-B (PDGF-B), the role of PDGF-D in tumor progression or treatment is largely unknown. To this end, we determined the role of PDGF-D in breast cancer progression, metastasis, and response to chemotherapy. Experimental Design: We first examined PDGF-D expression in human breast carcinomas by immunohistochemical (IHC) staining. To mimic high PDGF-D expressing tumors, we stably transfected the breast cancer cell lines MDA-MB-231 and 4T1 with pdgf-d cDNA, and implanted these tumor cells orthtopically into nude mice. We monitored tumor growth by caliper measurement and bioluminescence imaging. We also used short hairpin RNA interference (shRNAi) and imatinib to block PDGF-D/PDGFR beta signaling. Finally, we studied the effect of PDGF-D on doxorubicin delivery and efficacy. Results: Human breast cancers express high levels of PDGF-D. Overexpression of PDGF-D promoted tumor growth and lymph node metastasis through increased proliferation, decreased apoptosis, and induction of CXCR4 expression. Blockade of CXCR4 signaling abolished PDGF-D-induced lymph node metastasis. Furthermore, overexpression of PDGF-D increased perivascular cell coverage and normalized tumor blood vessels. As a result, PDGF-D overexpression facilitated tissue penetration of doxorubicin and enhanced its treatment efficacy. Conclusions: PDGF-D is highly expressed in human breast cancer and facilitates tumor growth and lymph node metastasis, making it a potential target in breast cancer. At the same time, PDGF-D increases drug delivery and hence improves the efficacy of chemotherapy through vessel normalization. Therefore, judicious use of PDGF-D/PDGFR beta blockers would be necessary to minimize the adverse effects on concomitantly administered cytotoxic therapies. Clin Cancer Res; 17(11); 3638-48. (C)2011 AACR. C1 [Liu, Jieqiong; Liao, Shan; Huang, Yuhui; Samuel, Rekha; Naxerova, Kamila; Huang, Peigen; Kamoun, Walid; Jain, Rakesh K.; Fukumura, Dai; Xu, Lei] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Liu, Jieqiong] Cent S Univ, Xiangya Hosp 2, Dept Breast Surg, Changsha, Hunan, Peoples R China. [Shi, Tony] NYU, Coll Arts & Sci, New York, NY USA. RP Xu, L (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. EM lei@steele.mgh.harvard.edu RI Huang, Yuhui/E-5046-2010; OI Huang, Yuhui/0000-0002-6226-2028; Naxerova, Kamila/0000-0001-7744-5110; Huang, Yuhui/0000-0003-1985-3575 FU Clafflin Distinguished Scholar Award; Harvard Medical School; US National Cancer Institute [P01-CA80124, R01-CA85140, R01-CA96915, R01-CA115767, R01-CA126642]; US Department of Defense [W81XWH-10-1-0016] FX This study was supported in part by Clafflin Distinguished Scholar Award, Harvard Medical School (L. Xu), US National Cancer Institute grants P01-CA80124 (R. K. Jain and D. Fukumura), R01-CA85140 (R. K. Jain), R01-CA96915 (D. Fukumura), R01-CA115767 (R. K. Jain), R01-CA126642 (R. K. Jain), and US Department of Defense Breast Cancer Research Innovator Award-W81XWH-10-1-0016 (R.K. Jain). NR 37 TC 38 Z9 41 U1 5 U2 15 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 JUN 1 PY 2011 VL 17 IS 11 BP 3638 EP 3648 DI 10.1158/1078-0432.CCR-10-2456 PG 11 WC Oncology SC Oncology GA 772AC UT WOS:000291200800015 PM 21459800 ER PT J AU Andersson, A Srivastava, MK Harris-White, M Huang, M Zhu, L Elashoff, D Strieter, RM Dubinett, SM Sharma, S AF Andersson, Asa Srivastava, Minu K. Harris-White, Marni Huang, Min Zhu, Li Elashoff, David Strieter, Robert M. Dubinett, Steven M. Sharma, Sherven TI Role of CXCR3 Ligands in IL-7/IL-7R alpha-Fc-Mediated Antitumor Activity in Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; ANGIOGENESIS IN-VIVO; X-C-CHEMOKINE; DENDRITIC CELLS; MACROPHAGE POLARIZATION; INTERFERON-GAMMA; TUMOR-ANTIGENS; INTERLEUKIN-7; IL-7; CARCINOMA AB Purpose: We evaluated the utility of chimeric gamma c homeostatic cytokine, IL-7/IL-7R alpha-Fc, to restore host APC (antigen presenting cell) and T cell activities in lung cancer. Experimental Design: Utilizing murine lung cancer models we determined the antitumor efficacy of IL-7/IL-7R alpha-Fc. APC, T cell, cytokine analyses, neutralization of CXCL9, CXCL10, and IFN gamma were carried out to evaluate the mechanistic differences in the antitumor activity of IL-7/IL-7R alpha-Fc in comparison to controls. Results: IL-7/IL-7R alpha-Fc administration inhibited tumor growth and increased survival in lung cancer. Accompanying the tumor growth inhibition were increases in APC and T cell activities. In comparison to controls, IL-7/IL-7R alpha-Fc treatment of tumor bearing mice led to increased: (i) levels of CXCL9, CXCL10, IFN gamma, IL-12 but reduced IL-10 and TGF beta, (ii) tumor macrophage infiltrates characteristic of M1 phenotype with increased IL-12, iNOS but reduced IL-10 and arginase, (iii) frequencies of T and NK cells, (iv) T cell activation markers CXCR3, CD69 and CD127(low), (v) effector memory T cells, and (vi) T cell cytolytic activity against parental tumor cells. IL-7/IL-7R alpha-Fc treatment abrogated the tumor induced reduction in splenic functional APC activity to T responder cells. The CXCR3 ligands played an important role in IL-7/IL-7R alpha-Fc-mediated antitumor activity. Neutralization of CXCL9, CXCL10, or IFN gamma reduced CXCR3 expressing activated T cells infiltrating the tumor and abrogated IL-7/IL-7R alpha-Fc-mediated tumor growth inhibition. Conclusions: Our findings show that IL-7/IL-7R alpha-Fc promotes afferent and efferent antitumor responses in lung cancer. Clin Cancer Res; 17(11); 3660-72. (C)2011 AACR. C1 [Harris-White, Marni; Huang, Min; Zhu, Li; Dubinett, Steven M.; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA 90073 USA. [Strieter, Robert M.] Univ Virginia, Dept Med, Charlottesville, VA USA. [Harris-White, Marni] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Huang, Min; Zhu, Li; Dubinett, Steven M.; Sharma, Sherven] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Andersson, Asa; Srivastava, Minu K.; Huang, Min; Zhu, Li; Elashoff, David; Dubinett, Steven M.; Sharma, Sherven] Univ Calif Los Angeles, UCLA Lung Canc Res Program, Dept Med, Los Angeles, CA 90095 USA. RP Sharma, S (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA 90073 USA. EM ssharma@mednet.ucla.edu FU NIH [RO1 CA95686, RO1 CA126944]; University of California Los Angeles Lung Cancer Program; Department of Veterans Affairs; University of California [18FT-0165, 15RT-0207] FX This work was supported by: NIH Grants (RO1 CA95686 and RO1 CA126944), University of California Los Angeles Lung Cancer Program, Department of Veterans Affairs Medical Research Funds, and Tobacco Related Disease Program Award Program of University of California (18FT-0165 and 15RT-0207). NR 56 TC 15 Z9 17 U1 0 U2 6 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 JUN 1 PY 2011 VL 17 IS 11 BP 3660 EP 3672 DI 10.1158/1078-0432.CCR-10-3346 PG 13 WC Oncology SC Oncology GA 772AC UT WOS:000291200800017 PM 21636553 ER PT J AU Kanai, R Wakimoto, H Martuza, RL Rabkin, SD AF Kanai, Ryuichi Wakimoto, Hiroaki Martuza, Robert L. Rabkin, Samuel D. TI A Novel Oncolytic Herpes Simplex Virus that Synergizes with Phosphoinositide 3-kinase/Akt Pathway Inhibitors to Target Glioblastoma Stem Cells SO CLINICAL CANCER RESEARCH LA English DT Article ID MALIGNANT GLIOMA-CELLS; U(S)3 PROTEIN-KINASE; IN-VIVO; CANCER; MUTANT; VECTORS; APOPTOSIS; TUMORS; US3; HERPES-SIMPLEX-VIRUS-1 AB Purpose: To develop a new oncolytic herpes simplex virus (oHSV) for glioblastoma (GBM) therapy that will be effective in glioblastoma stem cells (GSC), an important and untargeted component of GBM. One approach to enhance oHSV efficacy is by combination with other therapeutic modalities. Experimental Design: MG18L, containing a U(S)3 deletion and an inactivating LacZ insertion in U(L)39, was constructed for the treatment of brain tumors. Safety was evaluated after intracerebral injection in HSV-susceptible mice. The efficacy of MG18L in human GSCs and glioma cell lines in vitro was compared with other oHSVs, alone or in combination with phosphoinositide-3-kinase (PI3K)/Akt inhibitors (LY294002, triciribine, GDC-0941, and BEZ235). Cytotoxic interactions between MG18L and PI3K/Akt inhibitors were determined using Chou-Talalay analysis. In vivo efficacy studies were conducted using a clinically relevant mouse model of GSC-derived GBM. Results: MG18L was severely neuroattenuated in mice, replicated well in GSCs, and had anti-GBM activity in vivo. PI3K/Akt inhibitors displayed significant but variable antiproliferative activities in GSCs, whereas their combination with MG18L synergized in killing GSCs and glioma cell lines, but not human astrocytes, through enhanced induction of apoptosis. Importantly, synergy was independent of inhibitor sensitivity. In vivo, the combination of MG18L and LY294002 significantly prolonged survival of mice, as compared with either agent alone, achieving 50% long-term survival in GBM-bearing mice. Conclusions: This study establishes a novel therapeutic strategy: oHSV manipulation of critical oncogenic pathways to sensitize cancer cells to molecularly targeted drugs. MG18L is a promising agent for the treatment of GBM, being especially effective when combined with PI3K/Akt pathway-targeted agents. Clin Cancer Res; 17(11); 3686-96. (C)2011 AACR. C1 [Rabkin, Samuel D.] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, 185 Cambridge St,CPZN-3800, Boston, MA 02114 USA. EM rabkin@helix.mgh.harvard.edu RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU NIH [NS-032677]; Department of Defense [W81XWH-07-1-0359] FX The study was supported by NIH grant NS-032677 (R.L. Martuza) and Department of Defense grant W81XWH-07-1-0359 (S.D. Rabkin). NR 47 TC 30 Z9 30 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2011 VL 17 IS 11 BP 3686 EP 3696 DI 10.1158/1078-0432.CCR-10-3142 PG 11 WC Oncology SC Oncology GA 772AC UT WOS:000291200800019 PM 21505062 ER PT J AU Pharoah, PDP Palmieri, RT Ramus, SJ Gayther, SA Andrulis, IL Anton-Culver, H Antonenkova, N Antoniou, AC Goldgar, D Beattie, MS Beckmann, MW Birrer, MJ Bogdanova, N Bolton, KL Brewster, W Brooks-Wilson, A Brown, R Butzow, R Caldes, T Caligo, MA Campbell, I Chang-Claude, J Chen, YA Cook, LS Couch, FJ Cramer, DW Cunningham, JM Despierre, E Doherty, JA Dork, T Durst, M Eccles, DM Ekici, AB Easton, D Fasching, PA de Fazio, A Fenstermacher, DA Flanagan, JM Fridley, BL Friedman, E Gao, B Sinilnikova, O Gentry-Maharaj, A Godwin, AK Goode, EL Goodman, MT Gross, J Hansen, TVO Harnett, P Rookus, M Heikkinen, T Hein, R Hogdall, C Hogdall, E Iversen, ES Jakubowska, A Johnatty, SE Karlan, BY Kauff, ND Kaye, SB Chenevix-Trench, G Kelemen, LE Kiemeney, LA Kjaer, SK Lambrechts, D LaPolla, JP Lazaro, C Le, ND Leminen, A Leunen, K Levine, DA Lu, Y Lundvall, L Macgregor, S Marees, T Massuger, LF McLaughlin, JR Menon, U Montagna, M Moysich, KB Narod, SA Nathanson, KL Nedergaard, L Ness, RB Nevanlinna, H Nickels, S Osorio, A Paul, J Pearce, CL Phelan, CM Pike, MC Radice, P Rossing, MA Schildkraut, JM Sellers, TA Singer, CF Song, HL Stram, DO Sutphen, R Lindblom, A Terry, KL Tsai, YY van Altena, AM Vergote, I Vierkant, RA Vitonis, AF Walsh, C Wang-Gohrke, S Wappenschmidt, B Wu, AH Ziogas, A Berchuck, A Risch, HA AF Pharoah, Paul D. P. Palmieri, Rachel T. Ramus, Susan J. Gayther, Simon A. Andrulis, Irene L. Anton-Culver, Hoda Antonenkova, Natalia Antoniou, Antonis C. Goldgar, David Beattie, Mary S. Beckmann, Matthias W. Birrer, Michael J. Bogdanova, Natalia Bolton, Kelly L. Brewster, Wendy Brooks-Wilson, Angela Brown, Robert Butzow, Ralf Caldes, Trinidad Caligo, Maria Adelaide Campbell, Ian Chang-Claude, Jenny Chen, Y. Ann Cook, Linda S. Couch, Fergus J. Cramer, Daniel W. Cunningham, Julie M. Despierre, Evelyn Doherty, Jennifer A. Doerk, Thilo Duerst, Matthias Eccles, Diana M. Ekici, Arif B. Easton, Douglas Fasching, Peter A. de Fazio, Anna Fenstermacher, David A. Flanagan, James M. Fridley, Brooke L. Friedman, Eitan Gao, Bo Sinilnikova, Olga Gentry-Maharaj, Aleksandra Godwin, Andrew K. Goode, Ellen L. Goodman, Marc T. Gross, Jenny Hansen, Thomas V. O. Harnett, Paul Rookus, Matti Heikkinen, Tuomas Hein, Rebecca Hogdall, Claus Hogdall, Estrid Iversen, Edwin S. Jakubowska, Anna Johnatty, Sharon E. Karlan, Beth Y. Kauff, Noah D. Kaye, Stanley B. Chenevix-Trench, Georgia Kelemen, Linda E. Kiemeney, Lambertus A. Kjaer, Susanne Krueger Lambrechts, Diether LaPolla, James P. Lazaro, Conxi Le, Nhu D. Leminen, Arto Leunen, Karin Levine, Douglas A. Lu, Yi Lundvall, Lene Macgregor, Stuart Marees, Tamara Massuger, Leon F. McLaughlin, John R. Menon, Usha Montagna, Marco Moysich, Kirsten B. Narod, Steven A. Nathanson, Katherine L. Nedergaard, Lotte Ness, Roberta B. Nevanlinna, Heli Nickels, Stefan Osorio, Ana Paul, Jim Pearce, Celeste Leigh Phelan, Catherine M. Pike, Malcolm C. Radice, Paolo Rossing, Mary Anne Schildkraut, Joellen M. Sellers, Thomas A. Singer, Christian F. Song, Honglin Stram, Daniel O. Sutphen, Rebecca Lindblom, Annika Terry, Kathryn L. Tsai, Ya-Yu van Altena, Anne M. Vergote, Ignace Vierkant, Robert A. Vitonis, Allison F. Walsh, Christine Wang-Gohrke, Shan Wappenschmidt, Barbara Wu, Anna H. Ziogas, Argyrios Berchuck, Andrew Risch, Harvey A. CA BCFR Investigators EMBRACE Investigators GEMO Study Collaborators HEBON Investigators KConFab Investigators Consortium Investigators Modifiers SWE-BRCA Investigators Ovarian Canc Assoc Consortium TI The Role of KRAS rs61764370 in Invasive Epithelial Ovarian Cancer: Implications for Clinical Testing SO CLINICAL CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; MUTATION CARRIERS; BREAST-CANCER; RISK; CONSORTIUM; SURVIVAL AB Purpose: An assay for the single-nucleotide polymorphism (SNP), rs61764370, has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'-UTR miRNA binding site of the KRAS oncogene and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published article, analyzing fewer than 1,000 subjects in total, has examined this association. Experimental Design: Risk association was evaluated in 8,669 cases of invasive EOC and 10,012 controls from 19 studies participating in the Ovarian Cancer Association Consortium, and in 683 cases and 2,044 controls carrying BRCA1 mutations from studies in the Consortium of Investigators of Modifiers of BRCA1/2. Prognosis association was also examined in a subset of five studies with progression-free survival (PFS) data and 18 studies with all-cause mortality data. Results: No evidence of association was observed between genotype and risk of unselected EOC (OR = 1.02, 95% CI: 0.95-1.10), serous EOC (OR = 1.08, 95% CI: 0.98-1.18), familial EOC (OR = 1.09, 95% CI: 0.78-1.54), or among women carrying deleterious mutations in BRCA1 (OR = 1.09, 95% CI: 0.88-1.36). There was little evidence for association with survival time among unselected cases (HR = 1.10, 95% CI: 0.99-1.22), among serous cases (HR = 1.12, 95% CI = 0.99-1.28), or with PFS in 540 cases treated with carboplatin and paclitaxel (HR = 1.18, 95% CI: 0.93-1.52). Conclusions: These data exclude the possibility of an association between rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer. Use of this SNP for ovarian cancer clinical risk prediction, therefore, seems unwarranted. Clin Cancer Res; 17(11); 3742-50. (C)2011 AACR. C1 [Risch, Harvey A.] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, Sch Med, New Haven, CT 06520 USA. [Wappenschmidt, Barbara] Univ Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany. [Wappenschmidt, Barbara] Univ Cologne, CIO, Cologne, Germany. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Lindblom, Annika; SWE-BRCA Investigators] Karolinska Univ Hosp, Stockholm, Sweden. [Singer, Christian F.] Med Univ Vienna, Div Special Gynecol, Vienna, Austria. [Radice, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy. [Paul, Jim] Univ Glasgow, Canc Res UK Clin Trials Unit, Glasgow, Lanark, Scotland. [Ness, Roberta B.] Univ Texas Sch Publ Hlth, Houston, TX USA. [Nathanson, Katherine L.] Univ Penn, Sch Med, Dept Med, Med Genet & Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Montagna, Marco] IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Lazaro, Conxi] Inst Catalan Oncol, Hereditary Canc Program, Barcelona, Spain. [LaPolla, James P.] Bayfront Med Ctr, Obstet & Gynecol Residency Program, St Petersburg, FL USA. [LaPolla, James P.] Womens Canc Associates, St Petersburg, FL USA. [Lambrechts, Diether] Vesalius Res Ctr VIB, Louvain, Belgium. [Lambrechts, Diether] Univ Leuven, Louvain, Belgium. [Massuger, Leon F.; van Altena, Anne M.] Radboud Univ Nijmegen, Med Ctr, Dept Gynecol, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, Lambertus A.; Marees, Tamara] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6525 ED Nijmegen, Netherlands. [Kelemen, Linda E.] Alberta Hlth Serv Canc Care, Dept Populat Hlth Res, Calgary, AB, Canada. [Chenevix-Trench, Georgia; KConFab Investigators] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Kaye, Stanley B.] Inst Canc Res, Med Sect, Sutton, Surrey, England. [Kauff, Noah D.] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA. [Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Johnatty, Sharon E.; Lu, Yi; Macgregor, Stuart; Consortium Investigators Modifiers] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Jakubowska, Anna] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland. [Rookus, Matti; HEBON Investigators] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Nedergaard, Lotte] Univ Copenhagen, Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark. [Hogdall, Estrid] Herlev Hosp, Mol Unit, Dept Pathol, Herlev, Denmark. [Hogdall, Estrid; Kjaer, Susanne Krueger] Danish Canc Soc, Inst Canc Epidemiol, Dept Viruses Hormones & Canc, Copenhagen, Denmark. [Hogdall, Claus; Kjaer, Susanne Krueger; Lundvall, Lene] Univ Copenhagen, Rigshosp, Juliane Marie Ctr, Gynecol Clin, DK-2100 Copenhagen, Denmark. [Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark. [Goodman, Marc T.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. [Sinilnikova, Olga; GEMO Study Collaborators] Federat Natl Ctr Lutte Canc, Canc Genet Network Grp Genet & Canc, Lyon, France. [Friedman, Eitan] Chaim Sheba Med Ctr, Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Friedman, Eitan] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [de Fazio, Anna; Gao, Bo; Harnett, Paul] Westmead Hosp, Westmead Millennium Inst, Westmead, NSW 2145, Australia. [de Fazio, Anna; Gao, Bo; Harnett, Paul] Univ Sydney, Westmead Inst Canc Res, Westmead, NSW 2145, Australia. [de Fazio, Anna; Gao, Bo] Westmead Hosp, Dept Gynaecol Oncol, Westmead, NSW 2145, Australia. [Easton, Douglas; EMBRACE Investigators] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England. [Eccles, Diana M.] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Duerst, Matthias] Univ Jena, Clin Obstet & Gynaecol, Jena, Germany. [Doherty, Jennifer A.; Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Despierre, Evelyn; Leunen, Karin; Vergote, Ignace] Univ Leuven, Univ Hosp Leuven, Dept Obstet & Gynaecol, Div Gynaecol Oncol, Leuven, Belgium. [Goode, Ellen L.] Mayo Clin, Coll Med, Div Epidemiol, Rochester, MN USA. [Fridley, Brooke L.; Vierkant, Robert A.] Mayo Clin, Coll Med, Div Biostat, Dept Hlth Sci Res, Rochester, MN USA. [Cunningham, Julie M.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA. [Sutphen, Rebecca] Univ S Florida, Coll Med, Dept Pediat, Tampa, FL 33612 USA. [Chen, Y. Ann; Fenstermacher, David A.; Phelan, Catherine M.; Sellers, Thomas A.; Tsai, Ya-Yu] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Chang-Claude, Jenny; Hein, Rebecca; Nickels, Stefan] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Campbell, Ian] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Campbell, Ian] Peter MacCallum Canc Ctr, Ctr Canc Genom & Predict Med, Melbourne, Vic, Australia. [Caligo, Maria Adelaide] Univ Hosp Pisa, Sect Genet Oncol, Pisa, Italy. [Osorio, Ana] Spanish Natl Canc Ctr, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Caldes, Trinidad] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain. [Butzow, Ralf] Univ Helsinki, Dept Pathol, Helsinki, Finland. [Butzow, Ralf; Heikkinen, Tuomas; Leminen, Arto; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Menon, Usha] UCL, EGA Inst Womens Hlth, Dept Gynaecol Oncol, London, England. [Brown, Robert; Flanagan, James M.; Gentry-Maharaj, Aleksandra] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Epigenet Unit, London SW7 2AZ, England. [Brooks-Wilson, Angela] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. [Brewster, Wendy] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Bolton, Kelly L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Bogdanova, Natalia] Hannover Med Sch, Clin Radiat Oncol, D-3000 Hannover, Germany. [Bogdanova, Natalia; Doerk, Thilo] Hannover Med Sch, Clin Obstet & Gynaecol, D-3000 Hannover, Germany. [Cramer, Daniel W.; Terry, Kathryn L.; Vitonis, Allison F.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ekici, Arif B.] Friedrich Alexander Univ Erlangen Nuremberg, Inst Human Genet, Erlangen, Bavaria, Germany. [Beckmann, Matthias W.] Univ Hosp Erlangen, Dept Gynecol & Obstet, Erlangen, Germany. [Beattie, Mary S.] Univ Calif San Francisco, Dept Med, Canc Risk Program, San Francisco, CA USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Epidemiol, Canc Risk Program, San Francisco, CA 94143 USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Biostat, Canc Risk Program, San Francisco, CA 94143 USA. [Goldgar, David; BCFR Investigators] NCI, Breast Canc Family Registry, Epidemiol & Genet Res Program, DCCPS, Rockville, MD USA. [Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandrov, Minsk, Byelarus. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA. [Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada. [Andrulis, Irene L.] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, New York, NY USA. [Gross, Jenny; Karlan, Beth Y.; Walsh, Christine] Cedars Sinai Med Ctr, Samual Oschin Comprehens Canc Inst, Womens Canc Res Inst, Los Angeles, CA 90048 USA. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Ramus, Susan J.; Gayther, Simon A.; Pearce, Celeste Leigh; Pike, Malcolm C.; Stram, Daniel O.; Wu, Anna H.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Ramus, Susan J.; Gayther, Simon A.; Pearce, Celeste Leigh; Pike, Malcolm C.; Stram, Daniel O.; Wu, Anna H.] Univ So Calif, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA. [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA. [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Palmieri, Rachel T.; Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Pharoah, Paul D. P.; Song, Honglin] Univ Cambridge, Dept Oncol, Cambridge, England. RP Risch, HA (reprint author), Yale Univ, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, Sch Med, 60 Coll St, New Haven, CT 06520 USA. EM harvey.risch@yale.edu RI Tang, Macy/B-9798-2014; Harnett, Paul/D-4090-2014; deFazio, Anna/D-3939-2013; Marees, Tamara/D-9867-2011; Lester, Jenny/B-5933-2012; montagna, marco/E-2225-2012; Verdrengh, Evelien/H-4571-2012; Macgregor, Stuart/C-6442-2009; Ekici, Arif/C-3971-2013; Andrulis, Irene/E-7267-2013; McLaughlin, John/E-4577-2013; Radice, Paolo/O-3119-2013; Kiemeney, Lambertus/D-3357-2009; Brooks-Wilson, Angela/E-9399-2012; Osorio, Ana/I-4324-2014; Massuger, Leon/H-8072-2014; Jakubowska, Anna/O-8050-2014; campbell, Ian/F-6006-2011; Fridley, Brooke/D-8315-2015; van Altena, Anne/B-9824-2016; Dork, Thilo/J-8620-2012; Johnatty, Sharon/R-8890-2016; OI Harnett, Paul/0000-0001-7021-0642; deFazio, Anna/0000-0003-0057-4744; montagna, marco/0000-0002-4929-2150; Macgregor, Stuart/0000-0001-6731-8142; Kiemeney, Lambertus/0000-0002-2368-1326; Brooks-Wilson, Angela/0000-0003-1009-6408; Osorio, Ana/0000-0001-8124-3984; Fridley, Brooke/0000-0001-7739-7956; Johnatty, Sharon/0000-0002-7888-1966; Vierkant, Robert/0000-0001-6242-5221; Nathanson, Katherine/0000-0002-6740-0901; Kjaer, Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798; Kauff, Noah/0000-0001-7242-6156; Nevanlinna, Heli/0000-0002-0916-2976 FU Ovarian Cancer Research Fund; Breast Cancer Family Registry including Cancer Care Ontario; US NIH [5U01-CA069467, 5U01-CA069398, 5U01-CA069631, 5U01-CA069446, 5U01-CA069417, 5U01-CA069638, N02-PC45022]; National Cancer Plan-Action 29; NIH [5R01-CA054419, 5P50-CA105009, 5R01-CA112523]; Ligue National Contre le Cancer; Association Le cancer du sein, parlonsen; Association for International Cancer Research [AICR-07-0454]; German Federal Ministry of Education and Research; Programme of Clinical Biomedical Research [01 GB 9401]; state of Baden-Wurttemberg through the University of Ulm Medical [P.685]; German Cancer Research Center; Helsinki University Central Hospital; Academy of Finland; Finnish Cancer Society; US Army MRMC [DAMD 17-02-1-0669]; Ovarian Cancer Research Foundation; Roswell Park Alliance Foundation; Cancer Australia [628333]; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Council of Tasmania; Cancer Council of South Australia; Cancer Foundation of Western Australia; American Cancer Society [SIOP-06-258-01-CCE, CRTG-00-196-01-CCE]; L & S Milken Foundation; Mermaid 1; Danish Cancer Society; National Cancer Institute [5R01-CA061107, 5R01-CA122443, 5R01-CA076016, 5R01-CA058860, 5K07-CA092044]; Radboud University Nijmegen Medical Centre; Canadian Institutes of Health Research (CIHR); Workers' Compensation Board of British Columbia; Cancer Research UK [A6689]; Experimental Cancer Research Centres; Advanced Cancer Detection Center; Department of Defense [DAMD 17-98-1-8659]; Celma Mastry Ovarian Cancer Foundation; Canadian Institutes for Health Research; National Cancer Institute of Canada; Canadian Cancer Society; Lon V Smith Foundation [LVS-39420]; Eve Appeal; OAK Foundation; Department of Health's NIHR Biomedical Research Centre; California Cancer Research Program [00-01389V-20170, 2110200]; California Department of Health Services [050-E8709]; Wellcome Trust [076113]; Breast Cancer Research Foundation; Susan G. Komen for the Cure; Eileen Stein Jacoby Fund; Neve Foundation; Project Hope for Ovarian Cancer Research and Education; Australian National Breast Cancer Foundation; National Health and Medical Research Council of Australia FX The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund. Funding for the individual participating studies was provided by: cooperative agreements with the Breast Cancer Family Registry including Cancer Care Ontario, and US NIH grants 5U01-CA069467, 5U01-CA069398, 5U01-CA069631, 5U01-CA069446, 5U01-CA069417, 5U01-CA069638, and N02-PC45022 (BCFR); the National Cancer Plan-Action 29 for the support of Translational Research (BEL); NIH grants 5R01-CA054419 and 5P50-CA105009 (BWH); NIH grants 5R01-CA112523 and 5R01-CA087538 (DOV); the Ligue National Contre le Cancer, the Association "Le cancer du sein, parlonsen!" and research grant AICR-07-0454 from the Association for International Cancer Research (GEMO); the German Federal Ministry of Education and Research, the Programme of Clinical Biomedical Research grant 01 GB 9401, the state of Baden-Wurttemberg through the University of Ulm Medical Faculty grant P.685, and the German Cancer Research Center (GER); the Helsinki University Central Hospital Research Fund, Academy of Finland and the Finnish Cancer Society (HOC); NIH grants 5R01-CA095023, 5R01-CA126841, and 5R03-CA121881, US Army MRMC grant DAMD 17-02-1-0669, and grants from the Ovarian Cancer Research Foundation and the Roswell Park Alliance Foundation (HOP); grant 628333 from Cancer Australia and grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia (kConFab); American Cancer Society Early Detection Professorship grant SIOP-06-258-01-CCE and the L & S Milken Foundation (LAX); Mermaid 1, The Danish Cancer Society and the National Cancer Institute 5R01-CA061107 (MAL); National Cancer Institute 5R01-CA122443 (MAY); National Cancer Institute 5R01-CA076016 (NCO); an Investment Grant of the Radboud University Nijmegen Medical Centre (NTH); grants from the Canadian Institutes of Health Research (CIHR) and the Workers' Compensation Board of British Columbia (OVA); Cancer Research UK (SEA); Experimental Cancer Research Centres and Cancer Research UK A6689 (SRO); NIH grant 5R01-CA106414, American Cancer Society grant CRTG-00-196-01-CCE and an Advanced Cancer Detection Center Grant, Department of Defense grant DAMD 17-98-1-8659, and funding from the Celma Mastry Ovarian Cancer Foundation (TBO); Canadian Institutes for Health Research, the National Cancer Institute of Canada, the Canadian Cancer Society and the NIH grants 5R01-CA063682 and 5R01-CA063678 (TOR); National Cancer Institute grants 5R01-CA058860 and 5K07-CA092044 and the Lon V Smith Foundation LVS-39420 (UCI); Cancer Research UK, the Eve Appeal, the OAK Foundation and the Department of Health's NIHR Biomedical Research Centre funding scheme (UKO); the California Cancer Research Program grants 00-01389V-20170 and 2110200, NIH grants 5P30-CA014089, 5P01-CA017054, 5R01-CA061132, 5R01-CA063464, N01-PC67010, and 5R03-CA113148, and California Department of Health Services sub-contract 050-E8709 (USC); Wellcome Trust award 076113 (WTCCC). Additional support for the TOR, NCO, MAY, TBO, and NCI studies was provided by NIH grant 5R01-CA114343. The Consortium of Investigators of Modifiers of BRCA1/2 GWAS and its participating studies were funded by: the Breast Cancer Research Foundation, Susan G.; Komen for the Cure, the Ovarian Cancer Research Fund, the Eileen Stein Jacoby Fund, NIH grants 5R01-CA128978 and 1R01-CA140323, Cancer Research UK, he Neve Foundation, Project Hope for Ovarian Cancer Research and Education, the Australian National Breast Cancer Foundation, the National Health and Medical Research Council of Australia. NR 16 TC 31 Z9 33 U1 0 U2 17 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 JUN 1 PY 2011 VL 17 IS 11 BP 3742 EP 3750 DI 10.1158/1078-0432.CCR-10-3405 PG 9 WC Oncology SC Oncology GA 772AC UT WOS:000291200800025 PM 21385923 ER PT J AU Abdelsamie, SA Li, YC Huang, Y Lee, MH Klein, RL Virella, G Lopes-Virella, MF AF Abdelsamie, Souzan A. Li, Yanchun Huang, Yan Lee, Mi-Hye Klein, Richard L. Virella, Gabriel Lopes-Virella, Maria F. TI Oxidized LDL immune complexes stimulate collagen IV production in mesangial cells via Fc gamma receptors I and III SO CLINICAL IMMUNOLOGY LA English DT Article DE Collagen; Low-density lipoprotein; Immune complexes; Nephropathy; Mesangial cells ID LOW-DENSITY-LIPOPROTEIN; DIABETIC-NEPHROPATHY; CULTURED RAT; EXTRACELLULAR-MATRIX; PATHOGENESIS; MACROPHAGES; DISEASE; PROGRESSION; EXPRESSION; ANTIBODIES AB Diabetic nephropathy is characterized by progressive mesangial expansion. Although we have reported that circulating oxidized LDL-containing immune complexes (oxLDL-IC) are associated with abnormal levels of albuminuria, the underlying mechanisms have not been investigated. In this study, we have studied the effect of oxLDL-IC on collagen IV expression by mesangial cells. We found that oxLDL-IC markedly stimulated collagen IV expression in a concentration- and time-dependent fashion while oxLDL only had moderate effect. We also found that oxLDL-IC stimulated collagen IV expression by engaging Fc gamma receptor (Fc gamma R) I and III, but not Fc gamma RII, and that p38 MAPK, JNK and PKC pathways were involved in collagen IV expression. Furthermore, we found that oxLDL-IC stimulated Fc gamma RI expression, suggesting a positive feedback mechanism involved in oxLDL-IC-stimulated collagen IV expression. Taken together, this study showed that oxLDL-IC stimulated collagen IV in mesangial cells via Fc gamma RI and Fc gamma RIII, and the expression of Fc gamma RI was increased by oxLDL-IC. Published by Elsevier Inc. C1 [Huang, Yan; Klein, Richard L.; Lopes-Virella, Maria F.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Abdelsamie, Souzan A.; Li, Yanchun; Huang, Yan; Lee, Mi-Hye; Klein, Richard L.; Lopes-Virella, Maria F.] Med Univ S Carolina, Coll Med, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM virellam@musc.edu FU Department of Veterans Affairs; National Institutes of Health/NHLBI [PO1 HL 55782]; NIH/NIDDK [R01 DK081352]; Juvenile Diabetes Foundation [2006-49] FX This work was supported by a Merit Review Grant from the Department of Veterans Affairs. This work was also supported by a Program Project funded by the National Institutes of Health/NHLBI (PO1 HL 55782), by a RO1 Grant funded by NIH/NIDDK (R01 DK081352) and by a Juvenile Diabetes Foundation Grant (2006-49). NR 42 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2011 VL 139 IS 3 BP 258 EP 266 DI 10.1016/j.clim.2011.01.016 PG 9 WC Immunology SC Immunology GA 771QX UT WOS:000291176900006 PM 21439910 ER PT J AU Xu, YH Li, H Gao, RL Adeyemo, O Itkin, M Kaplan, DE AF Xu, Yanhui Li, Hong Gao, Rui Lin Adeyemo, Oluwasayo Itkin, Maxim Kaplan, David E. TI Expansion of interferon-gamma-producing multifunctional CD4+T-cells and dysfunctional CD8+T-cells by glypican-3 peptide library in hepatocellular carcinoma patients SO CLINICAL IMMUNOLOGY LA English DT Article DE Hepatocellular carcinoma; T-cells; Interferon-gamma; PD-1; CTLA-4 ID T-CELL RESPONSES; HEPATITIS-B-VIRUS; ALPHA-FETOPROTEIN; POSTOPERATIVE RECURRENCE; EFFECTOR FUNCTION; EX-VIVO; LIVER; EXPRESSION; CIRRHOSIS; CANCER AB Glypican-3 is a promising target for immunotherapy for hepatocellular carcinoma, but limited data exist regarding its immunogenicity in patients with diverse HLA types, immunogenicity for CD4(+) T-cells, and the impact of inhibitory co-stimulation on glypican-3-specific T-cells. Using a 15mer overlapping peptide library for glypican-3, PBMC from patients with HCC were assessed ex vivo and after short-term in vitro expansion for tumor antigen-specific T-cell responses with and without blockade of PD-1/PD-L1 and CTLA-4 signaling. Glypican-3-specific T-cells were undetectable ex vivo, but primarily IFN gamma(+)TNF alpha(+) CD4(+) T-cells expanded with short-term in vitro stimulation in 10/19 (52%) patients. Glypican-3-specific CD8(+) T-cells predominantly produced TNF alpha, but did not secrete IFN gamma nor degranulate. CTLA-4 and PD-1 blockade minimally impacted the cytokine secretion and proliferation of glypican-3-specific T-cells. These data suggest that CD8(+). T-cell-directed tumor vaccines in HCC may have limited potential for efficacy unless optimal co-stimulation conditions can be identified but CD4(+)-directed vaccines merit consideration. Published by Elsevier Inc. C1 [Kaplan, David E.] Philadelphia VA Med Ctr, Med & Res Serv, Philadelphia, PA 19104 USA. [Xu, Yanhui; Li, Hong; Gao, Rui Lin; Adeyemo, Oluwasayo; Kaplan, David E.] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Itkin, Maxim] Univ Penn, Philadelphia VA Med Ctr, Serv Radiol, Philadelphia, PA 19104 USA. [Itkin, Maxim] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. RP Kaplan, DE (reprint author), Philadelphia VA Med Ctr, Med & Res Serv, Res Bldg 21,A402A,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM dakaplan@mail.med.upenn.edu OI Kaplan, David E./0000-0002-3839-336X FU Veterans Health Administration; University of Pennsylvania FX This work was supported by the Research Career Development Award from the Veterans Health Administration (DEK) and academic development funds from the University of Pennsylvania. The content of this article does not reflect the views of the VA or of the US Government. NR 53 TC 8 Z9 10 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2011 VL 139 IS 3 BP 302 EP 313 DI 10.1016/j.clim.2011.02.014 PG 12 WC Immunology SC Immunology GA 771QX UT WOS:000291176900011 PM 21419713 ER PT J AU Liverant, GI Kamholz, BW Sloan, DM Brown, TA AF Liverant, Gabrielle I. Kamholz, Barbara W. Sloan, Denise M. Brown, Timothy A. TI Rumination in Clinical Depression: A Type of Emotional Suppression? SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Rumination; Depression; Emotion regulation; Acceptance ID GENERALIZED ANXIETY DISORDER; DSM-IV ANXIETY; STRESS SCALES DASS; MOOD DISORDERS; THOUGHT SUPPRESSION; COGNITIVE THERAPY; NEGATIVE AFFECT; STRUCTURAL RELATIONSHIPS; PSYCHOMETRIC PROPERTIES; REGULATION STRATEGIES AB This study examined the relationship between rumination and the use of other emotion-regulation strategies in a depressed sample. Sixty outpatients diagnosed with unipolar depression completed questionnaires and participated in a sad mood induction. The mood induction was used to investigate the relationship between the use of rumination and each of two theoretically relevant emotion-regulation strategies-suppression and acceptance. Findings demonstrated that rumination was positively associated with other types of suppression and negatively related to acceptance. Results offer tentative support for the conceptualization of rumination as a maladaptive, cognitive emotion-regulation strategy utilized by depressed individuals in an attempt to suppress their experience of negative emotion. Findings also suggest a potential mechanism of action for efficacious mindfulness and acceptance-based treatments for depression. C1 [Liverant, Gabrielle I.; Sloan, Denise M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Liverant, Gabrielle I.; Kamholz, Barbara W.; Sloan, Denise M.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Liverant, GI (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. EM Gabrielle.Liverant@va.gov NR 74 TC 19 Z9 19 U1 6 U2 21 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 JUN PY 2011 VL 35 IS 3 BP 253 EP 265 DI 10.1007/s10608-010-9304-4 PG 13 WC Psychology, Clinical SC Psychology GA 771OD UT WOS:000291169300008 ER PT J AU Moon, HS Matarese, G Brennan, AM Chamberland, JP Liu, XW Fiorenza, CG Mylvaganam, GH Abanni, L Carbone, F Williams, CJ De Paoli, AM Schneider, BE Mantzoros, CS AF Moon, Hyun-Seuk Matarese, Giuseppe Brennan, Aoife M. Chamberland, John P. Liu, Xiaowen Fiorenza, Christina G. Mylvaganam, Geetha H. Abanni, Luisa Carbone, Fortunata Williams, Catherine J. De Paoli, Alex M. Schneider, Benjamin E. Mantzoros, Christos S. TI Efficacy of Metreleptin in Obese Patients With Type 2 Diabetes: Cellular and Molecular Pathways Underlying Leptin Tolerance SO DIABETES LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; BLOOD-BRAIN-BARRIER; EXPRESSION; RECEPTOR; INSULIN; HUMANS; RESISTANCE; ADIPOSITY; THERAPY; TISSUES AB OBJECTIVE-Metreleptin has been efficacious in improving metabolic control in patients with lipodystrophy, but its efficacy has not been tested in obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-We studied the role of leptin in regulating the endocrine adaptation to long-term caloric deprivation and weight loss in obese diabetic subjects over 16 weeks in the context of a double-blinded, placebo-controlled, randomized trial. We then performed detailed interventional and mechanistic signaling studies in humans in vivo, ex vivo, and in vitro. RESULTS-In obese patients with diabetes, metreleptin administration for 16 weeks did not alter body weight or circulating inflammatory markers but reduced HbA(1c) marginally (8.01 +/- 0.93-7.96 +/- 1.12, P = 0.03). Total leptin, leptin-binding protein, and antileptin antibody levels increased, limiting free leptin availability and resulting in circulating free leptin levels of similar to 50 ng/mL. Consistent with clinical observations, all metreleptin signaling pathways studied in human adipose tissue and peripheral blood mononuclear cells were saturable at similar to 50 ng/mL, with no major differences in timing or magnitude of leptin-activated STAT3 phosphorylation in tissues from male versus female or obese versus lean humans in vivo, ex vivo, or in vitro. We also observed for the first time that endoplasmic reticulum (ER) stress in human primary adipocytes inhibits leptin signaling. CONCLUSIONS-In obese patients with diabetes, metreleptin administration did not alter body weight or circulating inflammatory markers but reduced HbA(1c) marginally. ER stress and the saturable nature of leptin signaling pathways play a key role in the development of leptin tolerance in obese patients with diabetes. Diabetes 60:1647-1656, 2011 C1 [Moon, Hyun-Seuk; Brennan, Aoife M.; Chamberland, John P.; Liu, Xiaowen; Fiorenza, Christina G.; Mylvaganam, Geetha H.; Williams, Catherine J.; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Matarese, Giuseppe; Abanni, Luisa; Carbone, Fortunata] Univ Naples Federico 2, Dipartimento Biol & Patol Cellulare & Mol, Ist Endoctinol & Oncol Spetimentale, Immunol Lab, Naples, Italy. [De Paoli, Alex M.] Amgen Inc, Thousand Oaks, CA USA. [Schneider, Benjamin E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Minimally Invas Surg, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Sect Endocrinol, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Moon, Hyun-Seuk/G-8576-2015; Carbone, Fortunata/K-3176-2016; OI Moon, Hyun-Seuk/0000-0002-5216-2090; Carbone, Fortunata/0000-0003-4299-6515; Chamberland, John/0000-0002-7862-1371; Matarese, Giuseppe/0000-0001-9429-0616 FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [DK081913, DK79929, DK58785, AG032030]; Veterans Affairs Merit Review grant; Beth Israel Deaconess Medical Center (BIDMC); EU; Telethon-Juvenile Diabetes Research Foundation [GJT08004]; ERC [202579]; Amgen [UL1-RR-025758, M01-RR-01032]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources; [F32-DK64550-01A1] FX The current study was supported by grant F32-DK64550-01A1 (G.K.S.); the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases grants DK081913, DK79929, DK58785, and AG032030 (C.S.M.); and a Veterans Affairs Merit Review grant (C.S.M.). The Mantzoros Laboratory is also supported by a discretionary grant from the Beth Israel Deaconess Medical Center (BIDMC). G.M. is supported by grants from the EU Ideas Programme, ERC-Starting Independent Grant "LeptinMS" 202579, and Telethon-Juvenile Diabetes Research Foundation Grant GJT08004. The studies were also supported by Amgen and grants UL1-RR-025758 and M01-RR-01032, Harvard Clinical and Translational Science Center, from the National Center for Research Resources. NR 27 TC 52 Z9 52 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2011 VL 60 IS 6 BP 1647 EP 1656 DI 10.2337/db10-1791 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 774FE UT WOS:000291369600001 PM 21617185 ER PT J AU Navaratna, D Guo, SZ Hayakawa, K Wang, XY Gerhardinger, C Lo, EH AF Navaratna, Deepti Guo, Shu-zhen Hayakawa, Kazhuhide Wang, Xiaoying Gerhardinger, Chiara Lo, Eng H. TI Decreased Cerebrovascular Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Brain SO DIABETES LA English DT Article ID ENDOTHELIAL-CELLS; ISCHEMIC-STROKE; ADVANCED GLYCATION; FACTOR BDNF; CORTEX CAPILLARIES; ALZHEIMERS-DISEASE; MELLITUS; DEMENTIA; RISK; HYPERGLYCEMIA AB OBJECTIVE-Diabetes is an independent risk fact or for stroke. However, the underlying mechanism of how diabetes confers that this risk is not fully understood. We hypothesize that secretion of neurotrophic factors by the cerebral endothelium, such as brain-derived neurotrophic factor (BDNF), is suppressed in diabetes. Consequently, such accrued neuroprotective deficits make neurons more vulnerable to injury. RESEARCH DESIGN AND METHODS-We examined BDNF protein levels in a streptozotocin-induced rat model of diabetes by Western blotting and immunohistochemistry. Levels of total and secreted BDNF protein were quantified in human brain microvascular endothelial cells after exposure to advanced glycation end product (AGE)-BSA by enzyme-linked immunosorbent assay and immunocytochemistry. In media transfer experiments, the neuroprotective efficacy of conditioned media from normal healthy endothelial cells was compared with AGE-treated endothelial cells in an in vitro hypoxic injury model. RESULTS-Cerebrovascular BDNF protein was reduced in the cortical endothelium in 6-month diabetic rats. Immunohistochemical analysis of 6-week diabetic brain sections showed that the reduction of BDNF occurs early after induction of diabetes. Treatment of brain microvascular endothelial cells with AGE caused a similar reduction in BDNF protein and secretion in an extracellular signal-related kinase-dependent manner. In media transfer experiments, conditioned media from AGE-treated endothelial cells were less neuroprotective against hypoxic injury because of a decrease in secreted BDNF. CONCLUSIONS-Taken together, our findings suggest that a progressive depletion of microvascular neuroprotection in diabetes elevates the risk of neuronal injury for a variety of central nervous system diseases, including stroke and neuro-degeneration. Diabetes 60:1789-1796, 2011 C1 [Navaratna, Deepti; Guo, Shu-zhen; Hayakawa, Kazhuhide; Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. [Gerhardinger, Chiara] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. EM lo@helix.mgh.edu FU National Institutes of Health [R37-NS-37074, R01-NS-56530, RC2-NS-69335, P01-NS-55014]; American Heart Association FX This work was supported by National Institutes of Health grants R37-NS-37074, R01-NS-56530, RC2-NS-69335, and P01-NS-55014, and a Bugher award and postdoctoral fellowship from the American Heart Association. NR 50 TC 32 Z9 34 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2011 VL 60 IS 6 BP 1789 EP 1796 DI 10.2337/db10-1371 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 774FE UT WOS:000291369600017 PM 21562076 ER PT J AU Shields, RK Kwak, EJ Potoski, BA Doi, Y Adams-Haduch, JM Silviera, FP Toyoda, Y Pilewski, JM Crespo, M Pasculle, AW Clancy, CJ Nguyen, MH AF Shields, Ryan K. Kwak, Eun J. Potoski, Brian A. Doi, Yohei Adams-Haduch, Jennifer M. Silviera, Fernando. P. Toyoda, Yoshiya Pilewski, Joseph M. Crespo, Maria Pasculle, A. William Clancy, Cornelius J. Nguyen, M. Hong TI High mortality rates among solid organ transplant recipients infected with extensively drug-resistant Acinetobacter baumannii: using in vitro antibiotic combination testing to identify the combination of a carbapenem and colistin as an effective treatment regimen SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Acinetobacter; Synergy; Colistin; Doripenem; Transplant ID POLYMYXIN-B; TIGECYCLINE; SYNERGY; PNEUMONIA AB Extensively drug-resistant (XDR) Acinetobacter baumannii infections caused 91% (10/11) mortality in transplant recipients. Isolates were colistin-susceptible initially, but susceptibility decreased during therapy in 40% (4/10). We tested antibiotic combinations against XDR Acinetobacter in vitro and demonstrated positive interactions for carbapenem colistin. Subsequently, 80% (4/5) of transplant patients were treated successfully with carbepenem-colistin regimens. Published by Elsevier Inc. C1 [Shields, Ryan K.; Kwak, Eun J.; Potoski, Brian A.; Doi, Yohei; Adams-Haduch, Jennifer M.; Silviera, Fernando. P.; Toyoda, Yoshiya; Pilewski, Joseph M.; Crespo, Maria; Pasculle, A. William; Clancy, Cornelius J.; Nguyen, M. Hong] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, Pittsburgh, PA 15213 USA. EM cjc76@pitt.edu RI Doi, Yohei/C-7110-2013 FU University of Pittsburgh School of Pharmacy; University of Pittsburgh, Department of Medicine FX The study was funded by the University of Pittsburgh School of Pharmacy and by seed support from the University of Pittsburgh, Department of Medicine to the Transplant Infectious Diseases Program (MHN and CJC). NR 26 TC 35 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUN PY 2011 VL 70 IS 2 BP 246 EP 252 DI 10.1016/j.diagmicrobio.2010.12.023 PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 771CQ UT WOS:000291135200014 PM 21353436 ER PT J AU Nair, G Kim, M Nagaoka, T Olson, DE Thule, PM Pardue, MT Duong, TQ AF Nair, Govind Kim, Moon Nagaoka, Tsukasa Olson, Darin E. Thule, Peter M. Pardue, Machelle T. Duong, Timothy Q. TI Effects of common anesthetics on eye movement and electroretinogram SO DOCUMENTA OPHTHALMOLOGICA LA English DT Article DE Anesthesia; Eye movement; ERG; fMRI; Magnetic resonance imaging ID DARK-ADAPTED ELECTRORETINOGRAM; OPTICAL COHERENCE TOMOGRAPHY; PEAK VELOCITY; PHYSIOPHARMACOLOGICAL INVESTIGATIONS; RAT ELECTRORETINOGRAM; URETHANE ANESTHESIA; SCATTERING CHANGES; RETINAL RESPONSES; NITROUS-OXIDE; BLOOD-FLOW AB High-resolution magnetic resonance imaging (MRI) provides non-invasive images of retinal anatomy, physiology, and function with depth-resolved laminar resolution. Eye movement and drift, however, could limit high spatial resolution imaging, and anesthetics that minimize eye movement could significantly attenuate retinal function. The aim of this study was to determine the optimal anesthetic preparations to minimize eye movement and maximize visual-evoked retinal response in rats. Eye movements were examined by imaging of the cornea with a charge-coupled device (CCD) camera under isoflurane, urethane, ketamine/xylazine, and propofol anesthesia at typical dosages in rats. Combination of the paralytic pancuronium bromide with isoflurane or ketamine/xylazine anesthesia was also examined for the eye movement studies. Visual-evoked retinal responses were evaluated using full-field electroretinography (ERG) under isoflurane, ketamine/xylazine, urethane, and ketamine/xylazine + pancuronium anesthesia in rats. The degree of eye movement, measured as displacement per unit time, was the smallest under 1% isoflurane + pancuronium anesthesia. The ketamine/xylazine groups showed larger dark-adapted ERG a- and b-waves than other anesthetics tested. The isoflurane group showed the shortest b-wave implicit times. Photopic ERGs in the ketamine/xylazine groups showed the largest b-waves with the isoflurane group showing slightly shorter implicit times at the higher flash intensities. Oscillatory potentials revealed an early peak in the isoflurane group compared with ketamine/xylazine and urethane groups. Pancuronium did not affect the a- and b-wave, but did increase oscillatory potential amplitudes. Compared with the other anesthetics tested here, ketamine/xylazine + pancuronium was the best combination to minimize eye movement and maximize retinal function. These findings should set the stage for further development and application of high-resolution functional imaging techniques, such as MRI, to study retinal anatomy, physiology, and function in anesthetized rats. C1 [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, Dept Physiol, San Antonio, TX 78229 USA. [Nair, Govind; Nagaoka, Tsukasa] Emory Univ, Div Neurosci, Yerkes Imaging Ctr, Atlanta, GA 30322 USA. [Nair, Govind] Univ Massachusetts, Sch Med, Grad Sch Biomed Sci, Worcester, MA USA. [Nair, Govind] Worcester Polytech Inst, Worcester, MA 01609 USA. [Nair, Govind; Kim, Moon; Nagaoka, Tsukasa; Olson, Darin E.; Thule, Peter M.; Pardue, Machelle T.] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Olson, Darin E.; Thule, Peter M.] Emory Univ, Div Endocrinol Metab & Lipids, Atlanta, GA 30322 USA. [Pardue, Machelle T.] Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. [Pardue, Machelle T.] Atlanta VA Med Ctr, Rehab R&D Ctr, Decatur, GA USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, Dept Ophthalmol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM mpardue@emory.edu; duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU NIH/NEI [R01 EY014211, EY018855]; Department of Veterans Affairs; Research to Prevent Blindness; NEI [P30EY006360]; Rehabilitation, Research and Development Service, Department of Veterans Affairs FX This work was supported by the NIH/NEI (R01 EY014211 and EY018855 to TQD) and MERIT awards from the Department of Veterans Affairs (TQD, MTP, DEO). We also thank Research to Prevent Blindness; NEI (P30EY006360); and Rehabilitation, Research and Development Service, Department of Veterans Affairs for their supports. NR 66 TC 18 Z9 18 U1 2 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0012-4486 J9 DOC OPHTHALMOL JI Doc. Ophthalmol. PD JUN PY 2011 VL 122 IS 3 BP 163 EP 176 DI 10.1007/s10633-011-9271-4 PG 14 WC Ophthalmology SC Ophthalmology GA 774NC UT WOS:000291392300005 PM 21519880 ER PT J AU Oberaigner, W Siebert, U AF Oberaigner, Willi Siebert, Uwe TI Do women with cancer have better survival as compared to men after adjusting for staging distribution? SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE cancer; gender; population based; prognosis; survival ID GENDER-DIFFERENCES; RELATIVE SURVIVAL; RECORD LINKAGE; RATES; ERRORS AB Background: Gender aspects in medicine are receiving increasing attention, namely also in oncology. For this reason, we decided to investigate whether for solid cancer sites women have better survival outcome than do men in the population of Tyrol, Austria. Methods: We conducted an observational population-based study in Tyrol. All solid cancer sites excluding non-melanoma skin cancer and sex-specific sites were analysed in total and all specific sites with more than 500 patients in the analysis. By the end of 2006, follow-up was ended. We applied a relative excess risk model, thus correcting for differences in life expectancy between women and men. Results: For all cancer sites combined, after adjusting for case mix, women had a relative excess risk of 0.95 (95% CI 0.91-0.99). For the following sites our analysis resulted in a relative excess risk statistically different from 1, namely for women as compared to men: head and neck without larynx 0.72 (95% CI 0.56-0.93), stomach 0.86 (95% CI 0.75-0.97) and lung 0.82 (95% CI 0.75-0.90). Conclusion: In a healthcare system with free access to diagnostics and therapy, after adjusting for staging distribution female cancer patients have a lesser excess mortality risk than do men for lung, stomach and head and neck cancer and also for all cancer sites combined after adjusting for case mix. C1 [Oberaigner, Willi] Tyrolean State Hosp Ltd, Dept Clin Epidemiol, Canc Registry Tyrol, Innsbruck, Austria. [Oberaigner, Willi; Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, UMIT, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth Informat Syst & Hlth Technol Asses, Hall In Tirol, Austria. [Oberaigner, Willi; Siebert, Uwe] Ctr Personalized Canc Med, Innsbruck, Austria. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Inst Technol Assessment, Sch Med, Boston, MA USA. RP Oberaigner, W (reprint author), TILAK GmbH, Canc Registry Tyrol, Anichstr 35, Innsbruck, Austria. EM willi.oberaigner@iet.at FU ONCOTYROL Center for Personalized Cancer Medicine; Federal Ministry for Transport Innovation and Technology (BMVIT); Federal Ministry of Economics and Labour/the Federal Ministry of Economy, Family and Youth (BMWA/BMWFJ); Tyrolean Future Foundation (TZS); UMIT, University for Health Sciences, Medical Informatics and Technology; TILAK-Hospital Holding Company FX This work was supported by the ONCOTYROL Center for Personalized Cancer Medicine. ONCOTYROL is a K1-COMET Center and funded by the Federal Ministry for Transport Innovation and Technology (BMVIT) and the Federal Ministry of Economics and Labour/the Federal Ministry of Economy, Family and Youth (BMWA/BMWFJ), the Tyrolean Future Foundation (TZS) and the State of Styria represented by the Styrian Business Promotion Agency (SFG) and supported by UMIT, University for Health Sciences, Medical Informatics and Technology and TILAK-Hospital Holding Company. NR 27 TC 5 Z9 5 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD JUN PY 2011 VL 21 IS 3 BP 387 EP 391 DI 10.1093/eurpub/ckq099 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 766UT UT WOS:000290812700029 PM 20650944 ER PT J AU Mortensen, EM AF Mortensen, E. M. TI Potential causes of increased long-term mortality after pneumonia SO EUROPEAN RESPIRATORY JOURNAL LA English DT Editorial Material ID COMMUNITY-ACQUIRED PNEUMONIA; HOSPITALIZATION; INTERLEUKIN-6; COHORT C1 [Mortensen, E. M.] Univ Texas Hlth Ctr San Antonio, Dept Med, S Texas Vet Hlth Care Syst, VERDICT Res Program, San Antonio, TX USA. RP Mortensen, EM (reprint author), VERDICT Res Program 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM mortensene@uthscsa.edu OI Mortensen, Eric/0000-0002-3880-5563 NR 20 TC 6 Z9 6 U1 0 U2 1 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD JUN PY 2011 VL 37 IS 6 BP 1306 EP 1307 DI 10.1183/09031936.00194110 PG 2 WC Respiratory System SC Respiratory System GA 771JE UT WOS:000291152200002 PM 21632829 ER PT J AU Kwon, JY Ellington, JK Marsland, D Gupta, S AF Kwon, John Y. Ellington, J. Kent Marsland, Daniel Gupta, Sanjeev TI Calcaneal Traction Pin Placement Simplified: A Cadaveric Study SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE Calcaneal Traction; Transcalcaneal Pin Placement ID ANATOMIC CONSIDERATIONS; ANKLE AB Background: The tibial neurovascular bundle and sural nerve are at risk with errant pin placement during transcalcaneal pin placement. The purpose of this study was to determine a relative safe zone using a single osseous landmark to establish a technique applicable in the presence of trauma. We describe the neural anatomy anatomically and radiographically, giving surgeons a reliable and relatively safe technique for transcalcaneal pin placement. Materials and Methods: Twenty-four cadavers were dissected for the major medial neurovascular structures and the sural nerve. The closest distance from the neurovascular structures to the posterior inferior calcaneus was measured. Results: The mean distance from the posterior inferior calcaneus to the closest major medial neurovascular structure was 3.4 cm (SD +/- 0.36; range, 2.6 to 4.1 cm). The mean distance to the sural nerve was 3.4 cm (SD +/- 0.54; range, 2.3 to 4.6 cm). According to the 95% confidence intervals, a relative safe zone of 3.1 cm as a radius from the posterior inferior calcaneus was determined. Conclusion: A relatively safe zone of 3.1 cm based on 95% confidence intervals as described as a radius from the posterior inferior calcaneus can be used for transcalcaneal pin placement in most cases without injury to the medial neurovascular bundle or sural nerve. However anatomic variation may result in the neurovascular bundle being within this zone. Clinical Relevance: We describe a surgical technique for reliable placement of a transcalcaneal pin within this relative safe zone and a safe distance from the closest neurovascular structure. C1 [Kwon, John Y.] Harvard Univ, Sch Med, Dept Orthoped Surg, Massachussetts Gen Hosp, Boston, MA 02115 USA. [Ellington, J. Kent] Ortho Carolina Foot & Ankle Inst, Charlotte, NC USA. [Marsland, Daniel] Johns Hopkins Univ, Int Ctr Orthopaed Adv, Dept Orthopaed Surg, Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. [Gupta, Sanjeev] Royal Prince Alfred Hosp, Sydney, NSW, Australia. RP Kwon, JY (reprint author), 300 W Lombard St,Apt 1308, Baltimore, MD 21201 USA. EM johnkwonmd@gmail.com NR 21 TC 2 Z9 2 U1 0 U2 1 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD JUN PY 2011 VL 32 IS 6 BP 651 EP 655 DI 10.3113/FAI.2011.0651 PG 5 WC Orthopedics SC Orthopedics GA 773IL UT WOS:000291300100016 PM 21733432 ER PT J AU Namjou, B Kothari, PH Kelly, JA Glenn, SB Ojwang, JO Adler, A Alarcon-Riquelme, ME Gallant, CJ Boackle, SA Criswell, LA Kimberly, RP Brown, E Edberg, J Stevens, AM Jacob, CO Tsao, BP Gilkeson, GS Kamen, DL Merrill, JT Petri, M Goldman, RR Vila, LM Anaya, JM Niewold, TB Martin, J Pons-Estel, BA Sabio, JM Callejas, JL Vyse, TJ Bae, SC Perrino, FW Freedman, BI Scofield, RH Moser, KL Gaffney, PM James, JA Langefeld, CD Kaufman, KM Harley, JB Atkinson, JP AF Namjou, B. Kothari, P. H. Kelly, J. A. Glenn, S. B. Ojwang, J. O. Adler, A. Alarcon-Riquelme, M. E. Gallant, C. J. Boackle, S. A. Criswell, L. A. Kimberly, R. P. Brown, E. Edberg, J. Stevens, A. M. Jacob, C. O. Tsao, B. P. Gilkeson, G. S. Kamen, D. L. Merrill, J. T. Petri, M. Goldman, R. R. Vila, L. M. Anaya, J-M Niewold, T. B. Martin, J. Pons-Estel, B. A. Sabio, J. M. Callejas, J. L. Vyse, T. J. Bae, S-C Perrino, F. W. Freedman, B. I. Scofield, R. H. Moser, K. L. Gaffney, P. M. James, J. A. Langefeld, C. D. Kaufman, K. M. Harley, J. B. Atkinson, J. P. CA BIOLUPUS Network GENLES Collaboration TI Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort SO GENES AND IMMUNITY LA English DT Article DE autoimmunity; SLE; TREX1 ID AICARDI-GOUTIERES-SYNDROME; GENOME-WIDE ASSOCIATION; DNA EXONUCLEASE TREX1; ERYTHEMATOSUS PATIENTS; AUTOIMMUNE-DISEASE; MUTATIONS; INTERFERONS; PROTEIN AB Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, the major mammalian 3'-5' exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi-Goutieres syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in similar to 8370 patients with SLE and similar to 7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P = 0.0008, OR = 1.73, 95% CI = 1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P = 2.99E-13, OR = 5.2, 95% CI = 3.18-8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis. Genes and Immunity (2011) 12, 270-279; doi:10.1038/gene.2010.73; published online 27 January 2011 C1 [Namjou, B.; Kelly, J. A.; Glenn, S. B.; Ojwang, J. O.; Adler, A.; Alarcon-Riquelme, M. E.; Merrill, J. T.; Scofield, R. H.; Moser, K. L.; Gaffney, P. M.; James, J. A.; Kaufman, K. M.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Kothari, P. H.; Atkinson, J. P.] Washington Univ, Sch Med, St Louis, MI USA. [Alarcon-Riquelme, M. E.; Gallant, C. J.] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden. [Alarcon-Riquelme, M. E.] Univ Granada Junta de Andalucia, Ctr Genom & Oncol Res Pfizer, Granada, Spain. [Boackle, S. A.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Criswell, L. A.] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA. [Kimberly, R. P.; Brown, E.; Edberg, J.] Univ Alabama, Birmingham, AL USA. [Stevens, A. M.] Univ Washington, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Jacob, C. O.] Univ So Calif, Lupus Genet Grp, Los Angeles, CA USA. [Tsao, B. P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Gilkeson, G. S.; Kamen, D. L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Petri, M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Goldman, R. R.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Anaya, J-M] Univ Rosario, Ctr Autoimmune Dis Res CREA, Bogota, Colombia. [Vila, L. M.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Niewold, T. B.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Pons-Estel, B. A.] Sanatorio Parque, Rosario, Argentina. [Martin, J.] Inst Biomed & Parasitol Lopez Neyra, Armilla, Spain. [Sabio, J. M.] Hosp Virgen Nieves, Dept Internal Med, Granada, Spain. [Callejas, J. L.] Hosp Clin San Cecilio, Dept Internal Med, Granada, Spain. [Vyse, T. J.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. [Bae, S-C] Hanyang Univ, Hosp Rheumat Dis, Seoul 133791, South Korea. [Bae, S-C] Hanyang Univ, Dept Internal Med, Div Rheumatol, Seoul 133791, South Korea. [Perrino, F. W.; Freedman, B. I.; Langefeld, C. D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Kaufman, K. M.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Harley, J. B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. RP Namjou, B (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM namjoub@omrf.org RI Vyse, Tim/G-3887-2011; Martin, Javier/B-8141-2008; Anaya, Juan-Manuel/J-1960-2016; OI Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario, Biblioteca/0000-0003-3491-9392; Kimberly, Robert/0000-0002-5330-3086; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154; Niewold, Timothy/0000-0003-3532-6660 FU NIH [AR042460, RR015577, AR048940, RR020143, AI24717, AR62277, R21AI070304, AR044804, AR02175, AR052300, K24 AR 002138, P60 2 AR30692, PO1 AR49084, UL1RR025741, CA141700-01]; Lupus Foundation of America; Alliance for Lupus Research; US Department of Veterans Affairs; Cerebral Retinal Vasculopathy Fund; National Center for Research Resources (NCRR) [NIH AR43727, UL1RR025005, UL1RR029882]; Kirkland Scholar Award; US Public Health Service National Center for Research Resources [M01 RR-00079]; European Science Foundation; Swedish Research Council; Swedish Association against Rheumatism; Swedish International Development Agency (SIDA); Gustaf Vth-80th jubilee Foundation; [HL083822]; [NS062069]; [AR33062]; [AR49084]; [5UL1RR02777]; [R01GM069962]; [67692] FX The cooperation of patients and normal control individuals involved in this study as well as physicians that provide samples is gratefully acknowledged. At the Oklahoma Medical Research Foundation, the work was supported by the NIH (AR042460, RR015577, AR048940, RR020143, AI24717, AR62277), Lupus Foundation of America, the Alliance for Lupus Research, the US Department of Veterans Affairs. At the Washington University School of Medicine (St Louis, MO, USA), the work was supported by grants (HL083822 (PHK), and NS062069 (JPA)), and the Cerebral Retinal Vasculopathy Fund. At the University of Alabama at Birmingham, the work was supported by grants AR33062 (RPK), AR49084 (RPK) and 5UL1RR02777. At the Johns Hopkins University School of Medicine, the work was supported by The Hopkins Lupus Cohort (NIH AR43727) and UL1RR025005 from the National Center for Research Resources (NCRR). At the University of Colorado, Denver School of Medicine, the work was supported by a NIH grant R21AI070304. At the Medical University of South Carolina, Charleston, USA, the project was supported by award number UL1RR029882 from the National Center for Research Resources. (The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health). At the Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, USA, the work was supported by Kirkland Scholar Award, US Public Health Service National Center for Research Resources, M01 RR-00079 and NIH grants AR044804, AR02175 and AR052300. At the Northwestern University, Feinberg School of Medicine, Chicago, IL, USA, the work was supported by NIH grants K24 AR 002138, P60 2 AR30692, PO1 AR49084 and UL1RR025741. At the Wake Forest University Health Sciences, Department of Biochemistry, the work was supported by R01GM069962 and Alliance for Lupus Research (67692) awards. We acknowledge grants from the European Science Foundation for the BIOLUPUS network, the Swedish Research Council, Swedish Association against Rheumatism, the Swedish International Development Agency (SIDA) and Gustaf Vth-80th jubilee Foundation to MEAR and the NIH grant CA141700-01. For GENLES: Argentina: Hugo R Scherbarth, MD; Pilar C Marino, MD; Estela L Motta, MD at Servicio de Reumatologia, Hospital Interzonal General de Agudos 'Dr Oscar Alende', Mar del Plata, Argentina. Susana Gamron, MD; Cristina Drenkard, MD; Emilia Menso, MD at Servicio de Reumatologia de la UHMI 1, Hospital Nacional de Clinicas, Universidad Nacional de Cordoba, Cordoba, Argentina. Alberto Allievi, MD; Guillermo A Tate, MD at Organizacion Medica de Investigacion, Buenos Aires, Argentina. Jose L Presas, MD at Hospital General de Agudos Dr Juan A Fernandez, Buenos Aires, Argentina. Simon A Palatnik, MD; Marcelo Abdala, MD; Mariela Bearzotti, PhD at Facultad de Ciencias Medicas, Universidad Nacional de Rosario y Hospital Provincial del Centenario, Rosario, Argentina. Alejandro Alvarellos, MD; Francisco Caeiro, MD; Ana Bertoli, MD at Servicio de Reumatologia, Hospital Privado, Centro Medico de Cordoba, Cordoba, Argentina. Sergio Paira, MD; Susana Roverano, MD at Hospital Jose M. Cullen, Santa Fe, Argentina. Cesar E Graf, MD; Estela Bertero, PhD at Hospital San Martin, Parana. Cesar Caprarulo, MD; Griselda Buchanan, PhD at Hospital Felipe Heras, Concordia, Entre Rios, Argentina.; Carolina Guilleron, MD; Sebastian Grimaudo, PhD; Jorge Manni, MD at Departamento de Inmunologia, Instituto de Investigaciones Medicas 'Alfredo Lanri', Buenos Aires, Argentina. Luis J Catoggio, MD; Enrique R Soriano, MD; Carlos D Santos, MD at Seccion Reumatologia, Servicio de Clinica Medica, Hospital Italiano de Buenos Aires y Fundacion Dr Pedro M Catoggio para el Progreso de la Reumatologia, Buenos Aires, Argentina. Cristina Prigione, MD; Fernando A Ramos, MD; Sandra M Navarro, MD at Servicio de Reumatologia, Hospital Provincial de Rosario, Rosario, Argentina. Guillermo A Berbotto, MD; Marisa Jorfen, MD; Elisa J Romero, PhD at Servicio de Reumatologia Hospital Escuela Eva Peron. Granadero Baigorria, Rosario, Argentina. Mercedes A Garcia, MD; Juan C Marcos MD; Ana I Marcos, MD at Servicio de Reumatologia, Hospital Interzonal General de Agudos General San Martin, La Plata. Carlos E Perandones, MD; Alicia Eimon, MD at Centro de Educacion Medica e Investigaciones Clinicas (CEMIC), Buenos Aires, Argentina. Cristina G Battagliotti, MD at Hospital de Ninos Dr Orlando Alassia, Santa Fe, Argentina. Peru is represented by: Dr Eduardo Acevedo and Dr Mariano Cucho, Hospital Nacional Guillermo Almenara Irigoyen, Lima, Peru. Mexico is represented by Dr Ignacio Garcia de la Torre, Hospital General de Occidente, Zapopan, Jalisco; Dr Mario Cardiel Rios, Hospital General Dr Miguel Silva, Morelia, Michoacan; Dr Jose Francisco Moctezuma, Hospital General de Mexico, Mexico, DF; Dr Marco Maradiaga Cecena, Hospital General de Culiacan, Culiacan, Sinaloa. The members of the BIOLUPUS network are: Sandra D'Alfonso, Department of Medical Sciences and IRCAD, University of Eastern Piedmont, Novara, Italy; Bernard R. Lauwerys, Cliniques Universitaires Saint-Luc, Universite catholique de Louvain, Bruxells, Belgium; Emoke Endreffy, Department of Pediatrics and Health Center, University of Szeged, Szeged, Hungary; Laszlo Kovacs, Department of Rheumatology, Albert Szent-Gyorgyi Clinical Centre, University of Szeged, Szeged, Hungary; Carlos Vasconcelos, Hospital Santo Antonio and ICBAS, Porto, Portugal; Berta Martins da Silva, UMIB/ICBAS, Immunogenetics laboratory, Universidado do Porto, Porto, Portugal; Inigo Rua Figueroa, Hospital Doctor Negrin, Las Palmas de Gran Canaria, Spain. Sandra D'Alfonso, Nadia Barizzone (Department of Medical Sciences and IRCAD, University of Eastern Piedmont, Novara, Italy); Gian Domenico Sebastiani (Azienda Ospedaliera San Camillo-Forlanini, Roma, Italy); Mauro Galeazzi, (Siena University, Siena, Italy) Maria Giovanna Danieli (Clinica Medica di Scienze Mediche e Chirurgiche, Universita Politecnica delle Marche, Ancona, Italy); Giovanni La Montagna (Rheumatology Unit Second University of Naples, Naples, Italy) and Maria Grazia Sabbadini (Vita-Salute San Raffaele University of Milan, Italy). NR 35 TC 100 Z9 102 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2011 VL 12 IS 4 BP 270 EP 279 DI 10.1038/gene.2010.73 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 772BU UT WOS:000291206100004 PM 21270825 ER PT J AU Dai, N Rapley, J Angel, M Yanik, MF Blower, MD Avruch, J AF Dai, Ning Rapley, Joseph Angel, Matthew Yanik, M. Fatih Blower, Michael D. Avruch, Joseph TI mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry SO GENES & DEVELOPMENT LA English DT Article DE mTOR; IMP2; amino acid-dependent phosphorylation; IGF2; mRNA translation; internal ribosome entry; type 2 diabetes ID GENOME-WIDE ASSOCIATION; K562 LEUKEMIA-CELLS; BINDING PROTEIN; DEPENDENT TRANSLATION; MAMMALIAN TARGET; GROWTH; RAPTOR; IDENTIFICATION; EXPRESSION; PATHWAY AB Variants in the IMP2 (insulin-like growth factor 2 [IGF2] mRNA-binding protein 2) gene are implicated in susceptibility to type 2 diabetes. We describe the ability of mammalian target of rapamycin (mTOR) to regulate the cap-independent translation of IGF2 mRNA through phosphorylation of IMP2, an oncofetal RNA-binding protein. IMP2 is doubly phosphorylated in a rapamycin-inhibitable, amino acid-dependent manner in cells and by mTOR in vitro. Double phosphorylation promotes IMP2 binding to the IGF2 leader 3 mRNA 5' untranslated region, and the translational initiation of this mRNA through eIF-4E- and 5' cap-independent internal ribosomal entry. Unexpectedly, the interaction of IMP2 with mTOR complex 1 occurs through mTOR itself rather than through raptor. Whereas depletion of mTOR strongly inhibits IMP2 phosphorylation in cells, comparable depletion of raptor has no effect; moreover, the ability of mTOR to phosphorylate IMP2 in vitro is unaffected by the elimination of raptor. Dual phosphorylation of IMP2 at the mTOR sites is evident in the mouse embryo, likely coupling nutrient sufficiency to IGF2 expression and fetal growth. Doubly phosphorylated IMP2 is also widely expressed in adult tissues, including islets of Langerhans. C1 [Dai, Ning; Rapley, Joseph; Blower, Michael D.; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Dai, Ning; Rapley, Joseph; Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Dai, Ning; Rapley, Joseph; Avruch, Joseph] Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. [Dai, Ning; Rapley, Joseph; Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Angel, Matthew; Yanik, M. Fatih] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Blower, Michael D.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu RI wang, hua/H-3345-2011 FU NIH [CA73818, DK17776, DK057521]; ARRA funds FX We thank T. Ding, Dr. S. Jacobs, Dr. O. Peroni, and Dr. D. Wrighting for assistance with mice; M. Lynch and Dr. E. Schmidt for assistance in sucrose density gradient methods; Dr. S. Vasudevan for suggestions regarding streptavidin-tagged mRNA isolation; Dr. N. Oshiro for discussions; Dr. F. C. Nielsen for IMP1, IMP2, and IMP3 antibodies; and Dr. J. Christiansen for the plasmids pcDNA-IGF-II-L3-luciferase and pcDNA-IGF-II-L4-luciferase. Torin1 was kindly provided by Drs. N. S. Gray and D. M. Sabatini. Human islets were a gift from Dr. J. Markmann and Dr. J. Lei. This work was supported by grants from the NIH (CA73818, DK17776, and DK057521) and ARRA funds. NR 53 TC 54 Z9 54 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 2011 VL 25 IS 11 BP 1159 EP 1172 DI 10.1101/gad.2042311 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 771JL UT WOS:000291152900007 PM 21576258 ER PT J AU Durrett, R Foo, J Leder, K Mayberry, J Michor, F AF Durrett, Rick Foo, Jasmine Leder, Kevin Mayberry, John Michor, Franziska TI Intratumor Heterogeneity in Evolutionary Models of Tumor Progression SO GENETICS LA English DT Article ID CLONAL EXPANSION; ESCHERICHIA-COLI; WAITING TIME; CANCER; MUTATIONS; POPULATIONS; RESISTANCE; DIVERSITY; SUBPOPULATION; ADAPTATION AB With rare exceptions, human tumors arise from single cells that have accumulated the necessary number and types of heritable alterations. Each such cell leads to dysregulated growth and eventually the formation of a tumor. Despite their monoclonal origin, at the time of diagnosis most tumors show a striking amount of intratumor heterogeneity in all measurable phenotypes; such heterogeneity has implications for diagnosis, treatment efficacy, and the identification of drug targets. An understanding of the extent and evolution of intratumor heterogeneity is therefore of direct clinical importance. In this article, we investigate the evolutionary dynamics of heterogeneity arising during exponential expansion of a tumor cell population, in which heritable alterations confer random fitness changes to cells. We obtain analytical estimates for the extent of heterogeneity and quantify the effects of system parameters on this tumor trait. Our work contributes to a mathematical understanding of intratumor heterogeneity and is also applicable to organisms like bacteria, agricultural pests, and other microbes. C1 [Durrett, Rick] Duke Univ, Dept Math, Durham, NC 27708 USA. [Foo, Jasmine; Leder, Kevin; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Foo, Jasmine; Leder, Kevin; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Mayberry, John] Univ Pacific, Dept Math, Stockton, CA 95211 USA. RP Durrett, R (reprint author), Duke Univ, Dept Math, Durham, NC 27708 USA. EM rtd@math.duke.edu; michor@jimmy.harvard.edu FU National Cancer Institute [U54CA143798]; National Science Foundation (NSF) [DMS 0704996, DMS 0739164] FX The authors thank Theresa Edmonds for exceptional research assistance. This work is supported by National Cancer Institute grant U54CA143798 (to J.F., K.L., and F.M.), National Science Foundation (NSF) grant DMS 0704996 (to R.D.), and NSF RTG grant DMS 0739164 (to J.M.). NR 47 TC 42 Z9 45 U1 1 U2 10 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 2011 VL 188 IS 2 BP 461 EP 477 DI 10.1534/genetics.110.125724 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 773XM UT WOS:000291344900018 PM 21406679 ER PT J AU Rauh-Hain, JA Growdon, WB Rodriguez, N Goodman, AK Boruta, DM Schorge, JO Horowitz, NS del Carmen, MG AF Rauh-Hain, J. Alejandro Growdon, Whitfield B. Rodriguez, Noah Goodman, A. K. Boruta, David M., II Schorge, John O. Horowitz, Neil S. del Carmen, Marcela G. TI Carcinosarcoma of the ovary: A case-control study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Carcinosarcoma ID MIXED MESODERMAL TUMORS; MULLERIAN TUMORS; PLATINUM; CANCER; CHEMOTHERAPY; EXPERIENCE; FEATURES AB Introduction. Carcinosarcoma of the ovary is a rare tumor with a grim prognosis. Chemotherapy for these tumors is chosen according to guidelines established for epithelial ovarian cancer (EOC). The purpose of this study is to compare response to chemotherapy and survival in patients with advanced stage carcinosarcoma of the ovary. Methods. We identified women with advanced carcinosarcoma of the ovary who underwent first-line platinum and taxane-based chemotherapy. Each case was matched to two women with serous EOC. Cases and controls were matched by age, stage, and year of diagnosis. The Kaplan-Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the log-rank test and Cox proportional hazards model. Results. Fifty women treated with first line platinum and taxane-based chemotherapy had advanced carcinosarcoma of the ovary and were selected as cases. The response rates to chemotherapy for cases and controls were 62% and 83% (P = 0.03), respectively. Median progression-free survival was 11 months (95% CI, 8 to 14 months) versus 16 months (95% CI, 12 to 21 months; P = 0.02) and median overall survival was 24 months (95% CI, 18 to 29 months) versus 41 months (95% CI, 33 to 49 months; P = 0.002) for cases and controls, respectively. Conclusion. Patients with advanced carcinosarcoma of the ovary have a poorer response to platinum and taxane-based first-line chemotherapy and worse survival, compared to patients with serous EOC. Aggressive surgical treatment may play an important role. However, other alternative systemic therapeutic approaches should be sought for patients with carcinosarcoma of the ovary. (C) 2011 Elsevier Inc. All rights reserved. C1 [Rauh-Hain, J. Alejandro; Growdon, Whitfield B.; Goodman, A. K.; Boruta, David M., II; Schorge, John O.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02114 USA. [Rauh-Hain, J. Alejandro; Rodriguez, Noah; Horowitz, Neil S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02115 USA. RP del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 22 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN 1 PY 2011 VL 121 IS 3 BP 477 EP 481 DI 10.1016/j.ygyno.2011.02.023 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 772NN UT WOS:000291240700010 PM 21420726 ER PT J AU Carchman, EH Rao, J Loughran, PA Rosengart, MR Zuckerbraun, BS AF Carchman, Evie H. Rao, Jayashree Loughran, Patricia A. Rosengart, Matthew R. Zuckerbraun, Brian S. TI Heme Oxygenase-1-Mediated Autophagy Protects Against Hepatocyte Cell Death and Hepatic Injury from Infection/Sepsis in Mice SO HEPATOLOGY LA English DT Article ID NF-KAPPA-B; HOST-DEFENSE; APOPTOSIS; INHIBITION; SEPSIS; SHOCK; MITOCHONDRIA; DYSFUNCTION; SURVIVAL; FAILURE AB Adaptive responses to sepsis are necessary to prevent organ failure and death. Cellular signaling responses that limit cell death and structural damage allow a cell to withstand insult from sepsis to prevent irreversible organ dysfunction. One such protective pathway to reduce hepatocellular injury is the up-regulation of heme oxygenase-1 (HO-1) signaling. HO-1 is up-regulated in the liver in response to multiple stressors, including sepsis and lipopolysaccharide (LPS), and has been shown to limit cell death. Another recently recognized rudimentary cellular response to injury is autophagy. The aim of these investigations was to test the hypothesis that HO-1 protects against hepatocyte cell death in experimental sepsis in vivo or LPS in vitro via induction of autophagy. These data demonstrate that both HO-1 and autophagy are up-regulated in the liver after cecal ligation and puncture (CLP) in C57BL/6 mice or in primary mouse hepatocytes after treatment with LPS (100 ng/mL). CLP or LPS results in minimal hepatocyte cell death. Pharmacological inhibition of HO-1 activity using tin protoporphyrin or knockdown of HO-1 prevents the induction of autophagic signaling in these models and results in increased hepatocellular injury, apoptosis, and death. Furthermore, inhibition of autophagy using 3-methyladenine or small interfering RNA specific to VPS34, a class III phosphoinositide 3-kinase that is an upstream regulator of autophagy, resulted in hepatocyte apoptosis in vivo or in vitro. LPS induced phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), in part, via HO-dependent signaling. Moreover, inhibition of p38 MAPK prevented CLP- or LPS-induced autophagy. Conclusion: Sepsis or LPS-induced autophagy protects against hepatocellular death, in part via an HO-1 p38 MAPK-dependent signaling. Further investigations are needed to elucidate how autophagic signaling prevents apoptosis and cell death. (HEPATOLOGY 2011;53:2053-2062) C1 [Carchman, Evie H.; Rao, Jayashree; Loughran, Patricia A.; Rosengart, Matthew R.; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Sch Med, Pittsburgh, PA 15213 USA. [Carchman, Evie H.; Rao, Jayashree; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, Dept Surg, Sch Med, NW653 MUH,3459 5th Ave, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu NR 23 TC 89 Z9 96 U1 2 U2 24 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2011 VL 53 IS 6 BP 2053 EP 2062 DI 10.1002/hep.24324 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 773KX UT WOS:000291307300029 PM 21437926 ER PT J AU Singal, AK Jampana, SC Anand, BS AF Singal, Ashwani K. Jampana, Sarat C. Anand, Bhupinderjit S. TI Comment on a Systematic Review of Randomized Trials of Peginterferon Alpha-2a Versus Peginterferon Alpha-2b in Chronic Hepatitis C SO HEPATOLOGY LA English DT Letter ID PEGYLATED INTERFERON ALPHA-2A; COINFECTED PATIENTS; PLUS RIBAVIRIN C1 [Singal, Ashwani K.] Univ Texas Med Branch, Dept Internal Med, Galveston, TX USA. [Singal, Ashwani K.; Jampana, Sarat C.] Univ Texas Med Branch, Div Gastroenterol, Galveston, TX USA. [Anand, Bhupinderjit S.] Baylor Coll Med, Dept Gastroenterol & Hepatol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Singal, AK (reprint author), Univ Texas Med Branch, Dept Internal Med, Galveston, TX USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2011 VL 53 IS 6 BP 2151 EP 2151 DI 10.1002/hep.24165 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 773KX UT WOS:000291307300056 PM 21538429 ER PT J AU Goetz, MB Rimland, D AF Goetz, Matthew Bidwell Rimland, David TI Effect of Expanded HIV Testing Programs on the Status of Newly Diagnosed HIV-Infected Patients in Two Veterans Health Administration Facilities: 1999-2009 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID ANTIRETROVIRAL THERAPY; UNITED-STATES; TRANSMISSION; PREVALENCE C1 [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Rimland, David] VA Med Ctr, Dept Med, Decatur, GA USA. [Rimland, David] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. RP Goetz, MB (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. OI Goetz, Matthew/0000-0003-4542-992X NR 12 TC 7 Z9 7 U1 1 U2 3 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 JUN 1 PY 2011 VL 57 IS 2 BP E23 EP E25 DI 10.1097/QAI.0b013e31821a0600 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 771MQ UT WOS:000291163100003 PM 21709450 ER PT J AU Kwon, YM Ostlere, SJ McLardy-Smith, P Athanasou, NA Gill, HS Murray, DW AF Kwon, Young-Min Ostlere, Simon J. McLardy-Smith, Peter Athanasou, Nicholas A. Gill, Harinderjit S. Murray, David W. TI "Asymptomatic" Pseudotumors After Metal-on-Metal Hip Resurfacing Arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE pseudotumors; metal-on-metal; hip resurfacing; metal ions ID INFLAMMATORY PSEUDOTUMOR; SURFACE REPLACEMENT; ION LEVELS; CHROMIUM; COBALT; BEARINGS; DIAMETER; IMPLANTS; BLOOD; WEAR AB Symptomatic abnormal periprosthetic soft-tissue reactions ("pseudotumors") have been reported after metal-on-metal hip resurfacing arthroplasty (MoMHRA). The aims of this study were (1) to determine the prevalence of asymptomatic pseudotumors after MoMHRA and (2) to measure metal ion levels in these patients. A total of 201 hips in 158 patients were evaluated at a mean follow-up of 61 months (range, 36-88) using ultrasound/magnetic resonance imaging and serum/hip aspirate cobalt and chromium measurements. Pseudotumors found in 7 patients (4%) were associated with significantly higher cobalt and chromium levels and inferior functional scores. Elevated levels of cobalt and chromium ions suggest that pseudotumors are associated with increased wear generated from metal-on-metal articulations. Clinicians need to be aware of pseudotumors as a differential diagnosis during clinical evaluation of MoMHRA patients, and further imaging such as ultrasound or magnetic resonance imaging is recommended to confirm the diagnosis. C1 [Kwon, Young-Min] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adult Reconstruct Surg Unit,Dept Orthopaed Surg, Boston, MA 02116 USA. [Ostlere, Simon J.; McLardy-Smith, Peter; Athanasou, Nicholas A.; Gill, Harinderjit S.; Murray, David W.] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Nuffield Orthopaed Ctr, Headington, England. RP Kwon, YM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adult Reconstruct Surg Unit,Dept Orthopaed Surg, 55 Fruit St,GRJ 1126, Boston, MA 02116 USA. RI Murray, David/D-7117-2011; Gill, Richie/A-9808-2011 OI Gill, Richie/0000-0002-7740-2062 FU NIHR Biomedical Research Unit at the Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre, Oxford, United Kingdom FX This work was supported by the institutional funding, the NIHR Biomedical Research Unit at the Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre, Oxford, United Kingdom. None of the authors have professional or financial affiliations that may be perceived to have biased the presentation. NR 37 TC 145 Z9 151 U1 0 U2 13 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUN PY 2011 VL 26 IS 4 BP 511 EP 518 DI 10.1016/j.arth.2010.05.030 PG 8 WC Orthopedics SC Orthopedics GA 772NF UT WOS:000291239900001 PM 20591612 ER PT J AU Talmo, CT Kwon, YM Freiberg, AA Rubash, HE Malchau, H AF Talmo, Carl T. Kwon, Young-Min Freiberg, Andrew A. Rubash, Harry E. Malchau, Henrik TI Management of Polyethylene Wear Associated With a Well-Fixed Modular Cement less Shell During Revision Total Hip Arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; revision; acetabular component; polyethylene; treatment options ID GALANTE ACETABULAR COMPONENTS; FOLLOW-UP; LINER; PROSTHESIS; 12-YEAR; 10-YEAR AB We identified 128 revision total hip arthroplasties from 1993 to 2005 involving a well-fixed Harris-Galante Porous (HGP)-I or HGP-II acetabular component with minimum 2-year post-revision follow-up. Three treatment cohorts were identified. Of the hips that underwent modular liner exchange at revision, 14 hips (25%) required re-revision of the acetabular component, 8 for liner dislodgement, 3 for osteolysis and poly-wear, 2 for dislocation, and 1 for aseptic loosening. Of the hips that underwent revision of the well-fixed shell, 4 (15%) required subsequent re-revision of the acetabular component; 2 for dislocation and 2 for aseptic loosening. Six hips (27%) in the cemented liner group were re-revised; 4 for dislocation and 2 for loosening. Complete revision of a well-fixed HGP acetabular component is more reliable than liner exchange or liner cementation. C1 [Kwon, Young-Min; Freiberg, Andrew A.; Rubash, Harry E.; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. [Kwon, Young-Min; Freiberg, Andrew A.; Rubash, Harry E.; Malchau, Henrik] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Talmo, Carl T.] New England Baptist Hosp, Boston, MA USA. RP Malchau, H (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUN PY 2011 VL 26 IS 4 BP 576 EP 581 DI 10.1016/j.arth.2010.05.028 PG 6 WC Orthopedics SC Orthopedics GA 772NF UT WOS:000291239900011 PM 20647163 ER PT J AU Srinivasan, VJ Atochin, DN Radhakrishnan, H Jiang, JY Ruvinskaya, S Wu, WC Barry, S Cable, AE Ayata, C Huang, PL Boas, DA AF Srinivasan, Vivek J. Atochin, Dmitriy N. Radhakrishnan, Harsha Jiang, James Y. Ruvinskaya, Svetlana Wu, Weicheng Barry, Scott Cable, Alex E. Ayata, Cenk Huang, Paul L. Boas, David A. TI Optical coherence tomography for the quantitative study of cerebrovascular physiology SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE hydrogen clearance; optical coherence tomography; optical imaging; vascular biology ID CEREBRAL-BLOOD-FLOW; ANGIOGRAPHY; SCATTERING; OXYGEN; CELL AB Doppler optical coherence tomography (DOCT) and OCT angiography are novel methods to investigate cerebrovascular physiology. In the rodent cortex, DOCT flow displays features characteristic of cerebral blood flow, including conservation along nonbranching vascular segments and at branch points. Moreover, DOCT flow values correlate with hydrogen clearance flow values when both are measured simultaneously. These data validate DOCT as a noninvasive quantitative method to measure tissue perfusion over a physiologic range. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1339-1345; doi:10.1038/jcbfm.2011.19; published online 2 March 2011 C1 [Srinivasan, Vivek J.; Radhakrishnan, Harsha; Ruvinskaya, Svetlana; Wu, Weicheng; Boas, David A.] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp,Dept Radiol,MGH MIT HMS, Charlestown, MA 02129 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA USA. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Jiang, James Y.; Barry, Scott; Cable, Alex E.] Thorlabs Inc, Newton, NJ USA. [Ayata, Cenk] Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Dept Radiol, Charlestown, MA USA. [Ayata, Cenk] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv & Neurosci Intens Care Unit, Boston, MA 02114 USA. RP Srinivasan, VJ (reprint author), Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp,Dept Radiol,MGH MIT HMS, Bldg 149,Room 2280,13th St, Charlestown, MA 02129 USA. EM vjsriniv@nmr.mgh.harvard.edu RI Radhakrishnan, Harsha/K-5557-2012; Atochin, Dmitriy/Q-3150-2016 FU NIH [R01-NS057476, R01-EB001954, R01-NS033335, R01-NS061505, P01NS055104, P50NS010828, K99NS067050]; AHA [SDG 0835344N, 11IRG5440002]; AFOSR [MFEL FA9550-07-1-0101] FX This study was supported by the NIH (R01-NS057476, R01-EB001954, R01-NS033335, R01-NS061505, P01NS055104, P50NS010828, and K99NS067050), the AHA (SDG 0835344N and 11IRG5440002), and the AFOSR (MFEL FA9550-07-1-0101). NR 22 TC 38 Z9 38 U1 1 U2 9 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 JUN PY 2011 VL 31 IS 6 BP 1339 EP 1345 DI 10.1038/jcbfm.2011.19 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 771HY UT WOS:000291149000002 PM 21364599 ER PT J AU Tanaka, Y Nagaoka, T Nair, G Ohno, K Duong, TQ AF Tanaka, Yoji Nagaoka, Tsukasa Nair, Govind Ohno, Kikuo Duong, Timothy Q. TI Arterial spin labeling and dynamic susceptibility contrast CBF MRI in postischemic hyperperfusion, hypercapnia, and after mannitol injection SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE arterial spin labeling; arterial transit time; cerebral blood flow; dynamic susceptibility contrast; permeability; spin-lattice relaxation-time constant ID CEREBRAL-BLOOD-FLOW; CAPILLARY WATER PERMEABILITY; SINGULAR-VALUE DECOMPOSITION; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; BRAIN-BARRIER; EMBOLIC STROKE; FUNCTIONAL MRI; TRANSIT-TIME; PERFUSION AB Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) are widely used to image cerebral blood flow (CBF) in stroke. This study examined how changes in tissue spin-lattice relaxation-time constant (T(1)), blood-brain barrier (BBB) permeability, and transit time affect CBF quantification by ASL and DSC in postischemic hyperperfusion in the same animals. In Group I (n = 6), embolic stroke rats imaged 48 hours after stroke showed regional hyperperfusion. In normal pixels, ASL- and DSC-CBF linearly correlated pixel-by-pixel. In hyperperfusion pixels, ASL-CBF was significantly higher than DSC-CBF pixel-by-pixel (by 25%). T1 increased from 1.76 +/- 0.14 seconds in normal pixels to 1.93 +/- 0.17 seconds in hyperperfusion pixels. Arterial transit time decreased from 300 milliseconds in normal pixels to 200 milliseconds in hyperperfusion pixels. Delta R(2)* profiles showed contrast-agent leakages in the hyperperfusion regions. In Group II (n = 3) in which hypercapnic inhalation was used to increase CBF without BBB disruption, CBF increased overall but ASL- and DSC-CBF remained linearly correlated. In Group III (n = 3) in which mannitol was used to break the BBB, ASL-CBF was significantly higher than DSC-CBF. We concluded that in normal tissue, ASL and DSC provide comparable quantitative CBF, whereas in postischemic hyperperfusion, ASL-CBF and DSC-CBF differed significantly because ischemia-induced changes in T1 and BBB permeability affected the two methods differently. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1403-1411; doi:10.1038/jcbfm.2010.228; published online 22 December 2010 C1 [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. [Tanaka, Yoji; Nagaoka, Tsukasa; Nair, Govind] Emory Univ, Yerkes Imaging Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Tanaka, Yoji; Ohno, Kikuo] Tokyo Med & Dent Univ, Dept Neurosurg, Tokyo, Japan. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU NINDS NIH HHS [R01 NS045879] NR 43 TC 19 Z9 21 U1 1 U2 1 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 JUN PY 2011 VL 31 IS 6 BP 1403 EP 1411 DI 10.1038/jcbfm.2010.228 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 771HY UT WOS:000291149000010 PM 21179070 ER PT J AU Rose, AJ Glickman, ME D'Amore, MM Orner, MB Berlowitz, D Kressin, NR AF Rose, Adam J. Glickman, Mark E. D'Amore, Meredith M. Orner, Michelle B. Berlowitz, Dan Kressin, Nancy R. TI Effects of Daily Adherence to Antihypertensive Medication on Blood Pressure Control SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID HYPERTENSIVE PATIENTS; PATIENT ADHERENCE; THERAPY; POPULATION; INTENSIFICATION; NONCOMPLIANCE; DISEASE; PERIOD AB Clinicians are often uncertain about how to manage elevated blood pressure (BP) when a patient reports that he/she has recently missed several doses of antihypertensive medications. While we know that better adherence can improve BP during several months, the magnitude of this relationship in the short term is poorly understood. The authors examined this issue using a group of patients who monitored adherence using a Medication Events Monitoring System (MEMS) cap and had BP measurements in the course of routine clinical practice. BP readings were compared following 7 days of excellent adherence (100%) or poor adherence (< 60%), omitting BP values following intermediate adherence. Using several different methods, BP following 7 days of excellent adherence was between 12/7 mm Hg and 15/8 mm Hg lower than after 7 days of poor adherence. Clinicians can use this effect size to calibrate their impressions of what the BP might have been with improved adherence. J Clin Hypertens (Greenwich). 2011;13:416-421. (C)2011 Wiley Periodicals, Inc. C1 [Rose, Adam J.; Glickman, Mark E.; Orner, Michelle B.; Berlowitz, Dan; Kressin, Nancy R.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Rose, Adam J.; D'Amore, Meredith M.; Berlowitz, Dan; Kressin, Nancy R.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Glickman, Mark E.; Berlowitz, Dan] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02118 USA. [Kressin, Nancy R.] VA Boston Hlth Care Syst, Boston, MA USA. RP Glickman, ME (reprint author), Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd 152, Bedford, MA 01730 USA. EM mg@bu.edu OI Kressin, Nancy/0000-0003-2767-4286; Glickman, Mark/0000-0003-3993-2801 FU National Institutes of Health [HL072814]; Department of Veterans Affairs, Health Services Research and Development Service; Department of Veterans Affairs, Health Services Research & Development Service [RCS 02-066-1] FX Drs Rose and Glickman contributed equally to this manuscript. This research was supported by a grant from the National Institutes of Health (HL072814, NR Kressin, PI). Dr Rose is supported by a career development award from the Department of Veterans Affairs, Health Services Research and Development Service. Dr Kressin is supported in part by a Research Career Scientist award from the Department of Veterans Affairs, Health Services Research & Development Service (RCS 02-066-1). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The authors have no conflicts of interest to disclose. NR 25 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JUN PY 2011 VL 13 IS 6 BP 416 EP 421 DI 10.1111/j.1751-7176.2011.00427.x PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 774OB UT WOS:000291394800005 PM 21649841 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI Analysis of Recent Papers in Hypertension SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article C1 [Bloch, Michael J.] Univ Nevada, St Marys Reg Med Ctr, Risk Reduct Ctr, Dept Internal Med,Sch Med, Reno, NV 89503 USA. [Basile, Jan N.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. RP Bloch, MJ (reprint author), Univ Nevada, St Marys Reg Med Ctr, Risk Reduct Ctr, Dept Internal Med,Sch Med, 645 N Arlington St,Suite 460, Reno, NV 89503 USA. EM mbloch@aol.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JUN PY 2011 VL 13 IS 6 BP 455 EP 457 DI 10.1111/j.1751-7176.2011.00470.x PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 774OB UT WOS:000291394800010 PM 21649846 ER PT J AU Wheeler, LA Trifonova, R Vrbanac, V Basar, E McKernan, S Xu, Z Seung, E Deruaz, M Dudek, T Einarsson, JI Yang, L Allen, TM Luster, AD Tager, AM Dykxhoorn, DM Lieberman, J AF Wheeler, Lee Adam Trifonova, Radiana Vrbanac, Vladimir Basar, Emre McKernan, Shannon Xu, Zhan Seung, Edward Deruaz, Maud Dudek, Tim Einarsson, Jon Ivar Yang, Linda Allen, Todd M. Luster, Andrew D. Tager, Andrew M. Dykxhoorn, Derek M. Lieberman, Judy TI Inhibition of HIV transmission in human cervicovaginal explants and humanized mice using CD4 aptamer-siRNA chimeras SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SMALL INTERFERING RNAS; MUCOSAL TRANSMISSION; BLT MICE; INFECTION; DELIVERY; GENE; REPLICATION; RESISTANCE; CELLS; CCR5 AB The continued spread of the HIV epidemic underscores the need to interrupt transmission. One attractive strategy is a topical vaginal microbicide. Sexual transmission of herpes simplex virus type 2 (HSV-2) in mice can be inhibited by intravaginal siRNA application. To overcome the challenges of knocking down gene expression in immune cells susceptible to HIV infection, we used chimeric RNAs composed of an aptamer fused to an siRNA for targeted gene knockdown in cells bearing an aptamer-binding receptor. Here, we showed that CD4 aptamer-siRNA chimeras (CD4-AsiCs) specifically suppress gene expression in CD4(+) T cells and macrophages in vitro, in polarized cervicovaginal tissue explants, and in the female genital tract of humanized mice. CD4-AsiCs do not activate lymphocytes or stimulate innate immunity. CD4-AsiCs that knock down HIV genes and/or CCR5 inhibited HIV infection in vitro and in tissue explants. When applied intravaginally to humanized mice, CD4-AsiCs protected against HIV vaginal transmission. Thus, CD4-AsiCs could be used as the active ingredient of a microbicide to prevent HIV sexual transmission. C1 [Wheeler, Lee Adam; Trifonova, Radiana; Basar, Emre; McKernan, Shannon; Xu, Zhan; Dykxhoorn, Derek M.; Lieberman, Judy] Harvard Univ, Childrens Hosp Boston, Sch Med, Immune Dis Inst, Boston, MA USA. [Wheeler, Lee Adam; Trifonova, Radiana; Basar, Emre; McKernan, Shannon; Xu, Zhan; Dykxhoorn, Derek M.; Lieberman, Judy] Harvard Univ, Childrens Hosp Boston, Sch Med, Program Cellular & Mol Med, Boston, MA USA. [Wheeler, Lee Adam] Harvard Univ, Sch Med, MD PhD Program Immunol, Boston, MA USA. [Vrbanac, Vladimir; Seung, Edward; Deruaz, Maud; Luster, Andrew D.; Tager, Andrew M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dudek, Tim; Allen, Todd M.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Einarsson, Jon Ivar] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yang, Linda] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Dykxhoorn, Derek M.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. RP Lieberman, J (reprint author), 200 Longwood Ave,WAB 255, Boston, MA 02115 USA. EM lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015; Allen, Todd/F-5473-2011 FU NIAID (NIH) [AI070302, AI090671]; Massachusetts Life Sciences Center; Harvard CFAR; Ragon Institute; Cancer Research Institute; Ryan Foundation; Point Foundation; Harvard CFAR Scholar award FX This work was supported by the NIAID (NIH grants AI070302 and AI090671), Massachusetts Life Sciences Center (to J. Lieberman), Harvard CFAR and Ragon Institute (to J. Lieberman, A.D. Luster, and A.M. Tager), predoctoral fellowships from the Cancer Research Institute and the Ryan Foundation (to L.A. Wheeler), a Point Foundation scholarship (to L.A. Wheeler), and a Harvard CFAR Scholar award (to R. Trifonova). We thank members of the Lieberman laboratory, N. Barteneva, K. Ketman, M. Manoharan, K. Charisse, C.M. Boutwell, S. Biswas, and P.T.N. Sarkis for scientific advice; E. Oliva for providing human tissue samples; H.S. Shin and S. Brooks for technical assistance; and the NIH AIDS Reagent Program, A. Engelman, and B. Vogelstein for reagents. NR 50 TC 113 Z9 117 U1 1 U2 17 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 JUN PY 2011 VL 121 IS 6 BP 2401 EP 2412 DI 10.1172/JCI45876 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 772LB UT WOS:000291234300038 PM 21576818 ER PT J AU Dougan, M Li, DA Neuberg, D Mihm, M Googe, P Wong, KK Dranoff, G AF Dougan, Michael Li, Danan Neuberg, Donna Mihm, Martin Googe, Paul Wong, Kwok-Kin Dranoff, Glenn TI A dual role for the immune response in a mouse model of inflammation-associated lung cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NF-KAPPA-B; GM-CSF; LINKING INFLAMMATION; STAT3 ACTIVATION; INTERFERON-GAMMA; EPITHELIAL-CELLS; IL-6 PRODUCTION; TUMOR-GROWTH; TUMORIGENESIS; PROGRESSION AB Lung cancer is the leading cause of cancer death worldwide. Both principal factors known to cause lung cancer, cigarette smoke and asbestos, induce pulmonary inflammation, and pulmonary inflammation has recently been implicated in several murine models of lung cancer. To further investigate the role of inflammation in the development of lung cancer, we generated mice with combined loss of IFN-gamma and the beta-common cytokines GM-CSF and IL-3. These immunodeficient mice develop chronic pulmonary inflammation and lung tumors at a high frequency. Examination of the relationship between these tumors and their inflammatory microenvironment revealed a dual role for the immune system in tumor development. The inflammatory cytokine IL-6 promoted optimal tumor growth, yet wild-type mice rejected transplanted tumors through the induction of adaptive immunity. These findings suggest a model whereby cytokine deficiency leads to oncogenic inflammation that combines with defective antitumor immunity to promote lung tumor formation, representing a unique system for studying the role of the immune system in lung tumor development. C1 [Dougan, Michael; Li, Danan; Wong, Kwok-Kin; Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dougan, Michael; Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Mihm, Martin] Harvard Univ, Sch Med, Boston, MA USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Neuberg, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Mihm, Martin] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Googe, Paul] Knoxville Dermatopathol Lab, Knoxville, TN 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 OI Googe, Paul/0000-0002-9185-3548; wong, kwok kin/0000-0001-6323-235X FU National Institute on Aging [F30AG030298]; Margaret A. Cunningham Immune Mechanisms of Cancer Research Fellowship; American Lung Association, United Against Lung Cancer; NIH [R01 CA122794, R01 CA140594, R01 CA143083] FX We thank Stephen Conley of Massachusetts General Hospital for help with photography. This work was supported by National Institute on Aging grant F30AG030298 and the Margaret A. Cunningham Immune Mechanisms of Cancer Research Fellowship (to M. Dougan); the American Lung Association, United Against Lung Cancer, and NIH grants R01 CA122794 and R01 CA140594 (to K.-K. Wong); and NIH grant R01 CA143083 (to G. Dranoff). NR 47 TC 45 Z9 46 U1 1 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2011 VL 121 IS 6 BP 2436 EP 2446 DI 10.1172/JCI44796 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 772LB UT WOS:000291234300042 PM 21537082 ER PT J AU Fujioka, M Tokano, H Fujioka, KS Okano, H Edge, ASB AF Fujioka, Masato Tokano, Hisashi Fujioka, Keiko Shiina Okano, Hideyuki Edge, Albert S. B. TI Generating mouse models of degenerative diseases using Ore/lox-mediated in vivo mosaic cell ablation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DIPHTHERIA-TOXIN-A; TRANSGENIC MICE; STEM-CELLS; REGENERATION; HOMEOSTASIS; EXPRESSION; PANCREAS; RECOVERY; HEARING; SYSTEM AB Most degenerative diseases begin with a gradual loss of specific cell types before reaching a threshold for symptomatic onset. However, the endogenous regenerative capacities of different tissues are difficult to study, because of the limitations of models for early stages of cell loss. Therefore, we generated a transgenic mouse line (Mos-iCsp3) in which a lox-mismatched Cre/lox cassette can be activated to produce a drug-regulated dimerizable caspase-3. Tissue-restricted Cre expression yielded stochastic Casp3 expression, randomly ablating a subset of specific cell types in a defined domain. The limited and mosaic cell loss led to distinct responses in 3 different tissues targeted using respective Cre mice: reversible, impaired glucose tolerance with normoglycemia in pancreatic beta cells; wound healing and irreversible hair loss in the skin; and permanent moderate deafness due to the loss of auditory hair cells in the inner ear. These mice will be important for assessing the repair capacities of tissues and the potential effectiveness of new regenerative therapies. C1 [Fujioka, Masato; Tokano, Hisashi; Fujioka, Keiko Shiina; Edge, Albert S. B.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Fujioka, Masato; Tokano, Hisashi; Fujioka, Keiko Shiina; Edge, Albert S. B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Fujioka, Masato; Okano, Hideyuki] Keio Univ, Sch Med, Dept Physiol, Tokyo 160, Japan. [Fujioka, Masato] Keio Univ, Sch Med, Dept Otolarnygol Head & Neck Surg, Tokyo 160, Japan. [Edge, Albert S. B.] Harvard & Massachusetts Inst Technol, Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA USA. RP Edge, ASB (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM albert_edge@meei.harvard.edu RI Hidokano, Hideyuki/J-5973-2013 FU National Institute on Deafness and Other Communicative Disorders [RO1 DC007174, R21 DC010440-01, P30 DC05209]; Japanese Ministry of Education, Culture, Sports, Science and Technology; Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research; Hamilton H. Kellogg and Mildred H Kellogg Charitable Trust FX We are grateful to K. Darrow for instruction on surgical methods, to K. Takahashi for instruction on histopathology of the skin, to the Dana-Farber Rodent Histopathology Core for assistance with histopathology of skin and pancreas, and to J. Forrester, C. Miller, and L. Liberman for technical assistance. We thank M.C. Liberman and A. Brugeaud for critical discussions. This work was supported by grants RO1 DC007174, R21 DC010440-01, and P30 DC05209 from the National Institute on Deafness and Other Communicative Disorders; by Grant-in-Aid for Young Scientists (B) from the Japanese Ministry of Education, Culture, Sports, Science and Technology to M. Fujioka; by Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research to M. Fujioka; and by the Hamilton H. Kellogg and Mildred H Kellogg Charitable Trust. NR 25 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2011 VL 121 IS 6 BP 2462 EP 2469 DI 10.1172/JCI45081 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 772LB UT WOS:000291234300045 PM 21576819 ER PT J AU Lazaro, E Kadie, C Stamegna, P Zhang, SC Gourdain, P Lai, NY Zhang, M Martinez, SA Heckerman, D Le Gall, S AF Lazaro, Estibaliz Kadie, Carl Stamegna, Pamela Zhang, Shao Chong Gourdain, Pauline Lai, Nicole Y. Zhang, Mei Martinez, Sergio A. Heckerman, David Le Gall, Sylvie TI Variable HIV peptide stability in human cytosol is critical to epitope presentation and immune escape SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID T-LYMPHOCYTE ESCAPE; MHC CLASS-I; VIRUS TYPE-1 INFECTION; ANTIGEN PRESENTATION; THIMET OLIGOPEPTIDASE; DEGRADATION; GAG; REPLICATION; SELECTION; PATHWAY AB Induction of virus-specific CD8(+) T cell responses is critical for the success of vaccines against chronic viral infections. Despite the large number of potential MHC-I-restricted epitopes located in viral proteins, MHC-I-restricted epitope generation is inefficient, and factors defining the production and presentation of MHC-I-restricted viral epitopes are poorly understood. Here, we have demonstrated that the half-lives of HIV-derived peptides in cytosol from primary human cells were highly variable and sequence dependent, and significantly affected the efficiency of cell recognition by CD8(+) T cells. Furthermore, multiple clinical isolates of HLA-associated HIV epitope variants displayed reduced half-lives relative to consensus sequence. This decreased cytosolic peptide stability diminished epitope presentation and CTL recognition, illustrating a mechanism of immune escape. Chaperone complexes including Hsp90 and histone deacetylase HDAC6 enhanced peptide stability by transient protection from peptidase degradation. Based on empirical results with 166 peptides, we developed a computational approach utilizing a sequence-based algorithm to estimate the cytosolic stability of antigenic peptides. Our results identify sequence motifs able to alter the amount of peptide available for loading onto MHC-I, suggesting potential new strategies to modulate epitope production from vaccine immunogens. C1 [Lazaro, Estibaliz; Stamegna, Pamela; Zhang, Shao Chong; Gourdain, Pauline; Lai, Nicole Y.; Zhang, Mei; Martinez, Sergio A.; Le Gall, Sylvie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA. [Kadie, Carl] Microsoft Res, eSci Res Grp, Redmond, WA USA. [Heckerman, David] Microsoft Res, eSci Res Grp, Los Angeles, CA USA. RP Le Gall, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, CNY Bldg 149,13th St, Boston, MA 02129 USA. EM sylvie_legall@hms.harvard.edu FU Bill and Melinda Gates Foundation; National Institute of Allergy and Infectious Diseases [P01 AI074415-01A1, AI074415-02S1] FX We would like to thank A. Brass, M. Brockman, D. Kaufman, D. Kavanagh, and X. Yu for critical reading of the manuscript. This project was funded by the Bill and Melinda Gates Foundation (Collaboration for AIDS Vaccine Discovery) and, for the study on immune escape (Table 3 and Figure 6), by the National Institute of Allergy and Infectious Diseases (P01 AI074415-01A1 and AI074415-02S1 ARRA supplement; Special Emphasis Panel Vaccine Design and Acute HIV Infection). NR 34 TC 26 Z9 26 U1 0 U2 1 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 JUN PY 2011 VL 121 IS 6 BP 2480 EP 2492 DI 10.1172/JCI44932 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 772LB UT WOS:000291234300047 PM 21555856 ER PT J AU Bezy, O Tran, TT Pihlajamaki, J Suzuki, R Emanuelli, B Winnay, J Mori, MA Haas, J Biddinger, SB Leitges, M Goldfine, AB Patti, ME King, GL Kahn, CR AF Bezy, Olivier Tran, Thien T. Pihlajamaki, Jussi Suzuki, Ryo Emanuelli, Brice Winnay, Jonathan Mori, Marcelo A. Haas, Joel Biddinger, Sudha B. Leitges, Michael Goldfine, Allison B. Patti, Mary Elizabeth King, George L. Kahn, C. Ronald TI PKC delta regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROTEIN-KINASE-C; DIET-INDUCED OBESITY; RECEPTOR SUBSTRATE-1; SKELETAL-MUSCLE; PHOSPHOINOSITIDE 3-KINASE; METABOLIC SYNDROME; GLUCOSE-TRANSPORT; OXIDATIVE STRESS; RESISTANT MICE; FATTY LIVER AB C57BL/6J and 129S6/Sv (B6 and 129) mice differ dramatically in their susceptibility to developing diabetes in response to diet- or genetically induced insulin resistance. A major locus contributing to this difference has been mapped to a region on mouse chromosome 14 that contains the gene encoding PKC delta. Here, we found that PKC delta expression in liver was 2-fold higher in B6 versus 129 mice from birth and was further increased in B6 but not 129 mice in response to a high-fat diet. PRKCD gene expression was also elevated in obese humans and was positively correlated with fasting glucose and circulating triglycerides. Mice with global or liver-specific inactivation of the Prkcd gene displayed increased hepatic insulin signaling and reduced expression of gluconeogenic and lipogenic enzymes. This resulted in increased insulin-induced suppression of hepatic gluconeogenesis, improved glucose tolerance, and reduced hepatosteatosis with aging. Conversely, mice with liver-specific overexpression of PKC delta developed hepatic insulin resistance characterized by decreased insulin signaling, enhanced lipogenic gene expression, and hepatosteatosis. Therefore, changes in the expression and regulation of PKC delta between strains of mice and in obese humans play an important role in the genetic risk of hepatic insulin resistance, glucose intolerance, and hepatosteatosis; and thus PKC delta may be a potential target in the treatment of metabolic syndrome. C1 [Bezy, Olivier; Tran, Thien T.; Suzuki, Ryo; Emanuelli, Brice; Winnay, Jonathan; Mori, Marcelo A.; Haas, Joel; Biddinger, Sudha B.; Goldfine, Allison B.; Patti, Mary Elizabeth; King, George L.; Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. [Bezy, Olivier; Tran, Thien T.; Suzuki, Ryo; Emanuelli, Brice; Winnay, Jonathan; Mori, Marcelo A.; Haas, Joel; Biddinger, Sudha B.; Goldfine, Allison B.; Patti, Mary Elizabeth; King, George L.; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Pihlajamaki, Jussi] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Pihlajamaki, Jussi] Univ Eastern Finland, Dept Clin Nutr, Kuopio, Finland. [Pihlajamaki, Jussi] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Biddinger, Sudha B.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Endocrinol, Boston, MA USA. [Leitges, Michael] Univ Oslo, Biotechnol Ctr Oslo, Oslo, Norway. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu RI Emanuelli, Brice/M-2097-2016 FU NIH [DK31036, DK33201]; American Diabetes Association FX The authors thank Michael Rourk and Graham Smith for animal technical assistance. This work was supported by the NIH grants DK31036 and DK33201, an American Diabetes Association mentor-based award, and the Mary K. Iacocca Professorship to C.R. Kahn. NR 54 TC 52 Z9 55 U1 1 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2011 VL 121 IS 6 BP 2504 EP 2517 DI 10.1172/JCI46045 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 772LB UT WOS:000291234300049 PM 21576825 ER PT J AU Hammond, SP Bialek, R Milner, DA Petschnigg, EM Baden, LR Marty, FM AF Hammond, Sarah P. Bialek, Ralf Milner, Danny A. Petschnigg, Eva M. Baden, Lindsey R. Marty, Francisco M. TI Molecular Methods To Improve Diagnosis and Identification of Mucormycosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FUNGAL-INFECTIONS; ZYGOMYCOSIS; TISSUE; ASPERGILLOSIS; AGENTS; ASSAYS; MODEL AB Mucormycosis is difficult to diagnose. Samples from suspected cases often fail to grow Mucorales in microbiologic cultures. We identified all hematologic malignancy and stem cell transplant patients diagnosed with proven mucormycosis between 2001 and 2009 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Seminested PCR targeting Mucorales 18S ribosomal DNA and sequencing were performed on formalin-fixed paraffin-embedded tissue samples. Of 29 cases of mucormycosis, 27 had tissue samples available for PCR and sequencing. Mucorales PCR was positive in 22. Among 12 culture-positive cases, 10 were PCR positive and sequencing was concordant with culture results to the genus level in 9. Among 15 culture-negative cases, PCR was positive and sequencing allowed genus identification in 12. Mucorales PCR is useful for confirmation of the diagnosis of mucormycosis and for further characterization of the infection in cases where cultures are negative. C1 [Hammond, Sarah P.; Petschnigg, Eva M.; Baden, Lindsey R.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Milner, Danny A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Hammond, Sarah P.; Baden, Lindsey R.; Marty, Francisco M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hammond, Sarah P.; Milner, Danny A.; Baden, Lindsey R.; Marty, Francisco M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bialek, Ralf] Labor Dr Krause & Kollegen MVZ, Kiel, Germany. RP Hammond, SP (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM shammond2@partners.org NR 12 TC 47 Z9 47 U1 0 U2 0 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 JUN PY 2011 VL 49 IS 6 BP 2151 EP 2153 DI 10.1128/JCM.00256-11 PG 3 WC Microbiology SC Microbiology GA 769NZ UT WOS:000291024500013 PM 21508149 ER PT J AU Hira, KG Mackay, MR Hempstead, AD Ahmed, S Karim, MM O'Connor, RM Hibberd, PL Calderwood, SB Ryan, ET Khan, WA Ward, HD AF Hira, Kirthi G. Mackay, Melanie R. Hempstead, Andrew D. Ahmed, Sabeena Karim, Mohammad M. O'Connor, Roberta M. Hibberd, Patricia L. Calderwood, Stephen B. Ryan, Edward T. Khan, Wasif A. Ward, Honorine D. TI Genetic Diversity of Cryptosporidium spp. from Bangladeshi Children SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PHYLOGENETIC ANALYSIS; CHILDHOOD DIARRHEA; PARVUM; ASSOCIATION; INFECTION; ANTIGEN; CLONING; EPIDEMIOLOGY; LIKELIHOOD; COMMUNITY AB The genetic diversity of Cryptosporidium spp. from infected children was characterized for the first time in Bangladesh. Seven C. hominis and C. parvum subtype families (including a new family, IIm) and 15 subtypes (including 2 new subtypes) were identified. The dominance of specific families and subtypes was different from that in other countries. C1 [Hira, Kirthi G.; Mackay, Melanie R.; O'Connor, Roberta M.; Hibberd, Patricia L.; Ward, Honorine D.] Tufts Med Ctr, Div Geog Med & Infect Dis, Boston, MA 02111 USA. [Hempstead, Andrew D.; Ward, Honorine D.] Tufts Med Ctr, Sackler Sch Grad Med Sci, Program Mol Microbiol, Boston, MA 02111 USA. [Ahmed, Sabeena; Karim, Mohammad M.; Khan, Wasif A.] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Ward, HD (reprint author), Tufts Med Ctr, Div Geog Med & Infect Dis, Box 041,800 Washington St, Boston, MA 02111 USA. EM hward@tuftsmedicalcenter.org FU National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) [UO1 AI45508, RO1 AI52786, U01 AI058935]; National Center for Complementary and Alternative Medicine, NIH [K24AT003683]; Fogarty International Center, NIH [D43TW005571]; National Institute of General Medical Sciences, NIH [T32 GM007310] FX This study was supported by an opportunity pool grant and in part by grants UO1 AI45508 (H. D. W.), RO1 AI52786 (H. D. W.), and U01 AI058935 (E. T. R. and S. B. C.), all from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), and K24AT003683 (P. L. H.) from the National Center for Complementary and Alternative Medicine, NIH. K. G. H. and M. R. M. were supported by grant D43TW005571 from the Fogarty International Center, NIH. A. D. H. is supported by grant T32 GM007310 from the National Institute of General Medical Sciences, NIH. NR 30 TC 7 Z9 7 U1 0 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 JUN PY 2011 VL 49 IS 6 BP 2307 EP 2310 DI 10.1128/JCM.00164-11 PG 4 WC Microbiology SC Microbiology GA 769NZ UT WOS:000291024500043 PM 21471344 ER PT J AU Chen, YH Chauhan, SK Saban, DR Sadrai, Z Okanobo, A Dana, R AF Chen, Yihe Chauhan, Sunil K. Saban, Daniel R. Sadrai, Zahra Okanobo, Andre Dana, Reza TI Interferon-gamma-secreting NK cells promote induction of dry eye disease SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE immunopathogenesis; antigen-presenting cells; ocular surface ID NATURAL-KILLER-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T-CELLS; INFLAMMATORY CYTOKINES; DESICCATING STRESS; DENDRITIC CELLS; PREVALENCE; SJOGRENS; FORMS; TH17 AB NK cells have been increasingly reported to be an important effector in autoimmune diseases. However, nothing is known in this regard in DED, the most common eye pathology, which is characterized by sustained inflammation on the ocular surface. In the present study, we have examined the profile of NK cells on the ocular surface as well as in the draining lymphoid tissues during the development of this disease. Our data demonstrate activated NK cells during the disease-induction phase. Moreover, in vivo depletion of NK cells in mice results in reduced disease severity and diminished proinflammatory cytokines. Furthermore, we show that NK cells are also able to modulate the maturation of APCs, which is correlated with IFN-gamma from NK cells. Together, our findings provide new in vivo evidence that IFN-gamma-secreting NK cells can promote induction of DED via direct target tissue damage and indirect influence on the priming phase of an adaptive immune response in secondary lymphoid tissue. J. Leukoc. Biol. 89: 965-972; 2011. C1 [Chen, Yihe; Chauhan, Sunil K.; Saban, Daniel R.; Sadrai, Zahra; Okanobo, Andre; Dana, Reza] Harvard Univ, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Med Sch, Boston, MA 02114 USA. RP Chen, YH (reprint author), Harvard Univ, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Med Sch, 20 Staniford St, Boston, MA 02114 USA. EM yihe.chen@schepens.harvard.edu FU National Institutes of Health [EY019098, EY20889]; Research to Prevent Blindness Lew R. Wasserman Merit Award FX This study was supported by National Institutes of Health EY019098 and EY20889 and the Research to Prevent Blindness Lew R. Wasserman Merit Award (R. D.). NR 34 TC 25 Z9 27 U1 0 U2 3 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 JUN PY 2011 VL 89 IS 6 BP 965 EP 972 DI 10.1189/jlb.1110611 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 770SI UT WOS:000291108400016 PM 21402771 ER PT J AU Sharman, MA Cohen-Adad, J Descoteaux, M Messe, A Benali, H Lehericy, S AF Sharman, Michael A. Cohen-Adad, Julien Descoteaux, Maxime Messe, Arnaud Benali, Habib Lehericy, Stephane TI Impact of Outliers on Diffusion Tensor and Q-Ball Imaging: Clinical Implications and Correction Strategies SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE diffusion; tensor; q-ball; imaging; magnetic resonance ID SPHERICAL DECONVOLUTION; MRI; TRACTOGRAPHY; ANISOTROPY; RESOLUTION; DISTORTION; GRADIENT; SCHEMES; MOTION AB Purpose: To measure the impact of corrupted images often found to occur in diffusion-weighted magnetic resonance imaging (DW-MRI). To propose a robust method for the correction of outliers, applicable to diffusion tensor imaging (DTI) and q-ball imaging (QBI). Materials and Methods: Monte Carlo simulations were carried out to measure the impact of outliers on DTI and QBI reconstruction in a single voxel. Methods to correct outliers based on q-space interpolation and direction removal were then implemented and validated in real image data. Results: Corruption in a single voxel led to clear variations in DTI and QBI metrics. In real data, the method of q-space interpolation was successful in identifying corrupted voxels and restoring them to values consistent with those of uncorrupted images. Conclusion: For images containing few gradient directions, where outlier removal was either impossible due to limited volumes or resulted in large changes in DTI/QBI metrics, q-space interpolation proved to be the method of choice for image restoration. A simple decision support system is proposed to assist clinicians in the correction of their corrupted DW data. C1 [Sharman, Michael A.; Lehericy, Stephane] Hop La Pitie Salpetriere, Ctr Neuroimaging Res CENIR, F-75651 Paris, France. [Sharman, Michael A.; Lehericy, Stephane] UPMC, INSERM, UMR S957, CRICM, Paris, Ile De France, France. [Cohen-Adad, Julien] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Cohen-Adad, Julien; Messe, Arnaud; Benali, Habib] UPMC, INSERM, UMR S678, Paris, France. [Descoteaux, Maxime] Univ Sherbrooke, Dept Comp Sci, Quebec City, PQ, Canada. [Messe, Arnaud; Benali, Habib] IFR 49, Paris, France. [Benali, Habib] Univ Montreal, CRIUGM, Unite Neuroimagerie Fonct, Montreal, PQ H3C 3J7, Canada. RP Sharman, MA (reprint author), Hop La Pitie Salpetriere, Ctr Neuroimaging Res CENIR, Batiment Paul Castaigne,Niveau 1,47-83 Blvd Hop, F-75651 Paris, France. EM michael.sharman@etu.upmc.fr OI Messe, Arnaud/0000-0001-9081-3088 FU European Union (EU) [6]; GENEPARK [LSH-2005-1.2.2-2] FX Contract grant sponsor: European Union (EU) Framework Project 6; Contract grant sponsor: GENEPARK: Genomic Biomarkers for Parkinson's Disease, Action Line: LIFESCIHEALTH Life sciences, genomics and biotechnology for health; Contract grant number: LSH-2005-1.2.2-2 Development of innovative methods for diagnosis of nervous system disorders. NR 42 TC 3 Z9 3 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2011 VL 33 IS 6 BP 1491 EP 1502 DI 10.1002/jmri.22577 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 772WD UT WOS:000291267700026 PM 21591020 ER PT J AU Cheung, JS Au, WY Ha, SY Kim, D Jensen, JH Zhou, IY Cheung, MM Wu, Y Guo, H Khong, PL Brown, TR Brittenham, GM Wu, EX AF Cheung, Jerry S. Au, Wing-Yan Ha, Shau-Yin Kim, Daniel Jensen, Jens H. Zhou, Iris Y. Cheung, Matthew M. Wu, Yin Guo, Hua Khong, Pek-Lan Brown, Truman R. Brittenham, Gary M. Wu, Ed X. TI Reduced Transverse Relaxation Rate (RR2) for Improved Sensitivity in Monitoring Myocardial Iron in Thalassemia SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MRI; cardiac MR; heart; RR2; thalassemia; iron overload; chelation therapy; ferritin; hemosiderin ID T2-ASTERISK-CARDIOVASCULAR MAGNETIC-RESONANCE; LIVER-BIOPSY SPECIMENS; NONINVASIVE MEASUREMENT; FERRITIN-LIKE; TISSUE-IRON; OVERLOAD; HEMOSIDERIN; QUANTIFICATION; SUSCEPTIBILITY; COMPLICATIONS AB Purpose: To evaluate the reduced transverse relaxation rate (RR2), a new relaxation index which has been shown recently to be primarily sensitive to intracellular ferritin iron, as a means of detecting short-term changes in myocardial storage iron produced by iron-chelating therapy in transfusion-dependent thalassemia patients. Materials and Methods: A single-breathhold multi-echo fast spin-echo sequence was implemented at 3 Tesla (T) to estimate RR2 by acquiring signal decays with interecho times of 5, 9 and 13 ms. Transfusion-dependent thalassemia patients (N = 8) were examined immediately before suspending iron-chelating therapy for 1 week (Day 0), after a 1-week suspension of chelation (Day 7), and after a 1-week resumption of chelation (Day 14). Results: The mean percent changes in RR2, R2, and R2* off chelation (between Day 0 and 7) were 11.9 +/- 8.9%, 5.4 +/- 7.7% and -4.4 +/- 25.0%; and, after resuming chelation (between Day 7 and 14), -10.6 +/- 13.9%, -8.9 +/- 8.0% and -8.5 +/- 24.3%, respectively. Significant differences in R2 and RR2 were observed between Day 0 and 7, and between Day 7 and 14, with the greatest proportional changes in RR2. No significant differences in R2* were found. Conclusion: These initial results demonstrate that significant differences in RR2 are detectable after a single week of changes in iron-chelating therapy, likely as a result of superior sensitivity to soluble ferritin iron, which is in close equilibrium with the chelatable cytosolic iron pool. RR2 measurement may provide a new means of monitoring the short-term effectiveness of iron-chelating agents in patients with myocardial iron overload. C1 [Cheung, Jerry S.; Zhou, Iris Y.; Cheung, Matthew M.; Wu, Yin; Guo, Hua; Wu, Ed X.] Univ Hong Kong, Lab Biomed Imaging & Signal Proc, Dept Elect & Elect Engn, Pokfulam, Hong Kong, Peoples R China. [Cheung, Jerry S.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Cheung, Jerry S.] Harvard Univ, Sch Med, Charlestown, MA USA. [Au, Wing-Yan] Univ Hong Kong, Dept Med, Pokfulam, Hong Kong, Peoples R China. [Ha, Shau-Yin] Univ Hong Kong, Dept Pediat & Adolescent Med, Pokfulam, Hong Kong, Peoples R China. [Kim, Daniel; Jensen, Jens H.] NYU, Sch Med, Dept Radiol, Ctr Biomed Imaging, New York, NY USA. [Guo, Hua] Tsinghua Univ, Dept Biomed Engn, Beijing 100084, Peoples R China. [Khong, Pek-Lan] Univ Hong Kong, Dept Diagnost Radiol, Pokfulam, Hong Kong, Peoples R China. [Brown, Truman R.] Columbia Univ, Dept Radiol & Biomed Engn, New York, NY USA. [Brittenham, Gary M.] Columbia Univ Coll Phys & Surg, Dept Pediat & Med, New York, NY 10032 USA. RP Wu, EX (reprint author), Univ Hong Kong, Lab Biomed Imaging & Signal Proc, Dept Elect & Elect Engn, Pokfulam, Hong Kong, Peoples R China. EM ewu@eee.hku.hk RI Zhou, Yuwen/D-8009-2013; Zhou, Iris Yuwen/A-2089-2017 OI Zhou, Iris Yuwen/0000-0002-4351-7398 FU Hong Kong Research Grant Council [GRF7794/07M]; Hong Kong Children Thalassaemia Foundation [2007/02]; National Institutes of Health [R01-DK069373, R01-DK066251, R37-DK049108, R01-DK049108]; American Heart Association [0730143N] FX Contract grant sponsor: Hong Kong Research Grant Council; Contract grant number: GRF7794/07M; Contract grant sponsor: Hong Kong Children Thalassaemia Foundation; Contract grant number: 2007/02; Contract grant sponsor: National Institutes of Health; Contract grant numbers: R01-DK069373, R01-DK066251, R37-DK049108, R01-DK049108; Contract grant sponsor: American Heart Association; Contract grant number: 0730143N. NR 41 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2011 VL 33 IS 6 BP 1510 EP 1516 DI 10.1002/jmri.22553 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 772WD UT WOS:000291267700028 PM 21591022 ER PT J AU Chan, CB Liu, X Pradoldej, S Hao, CH An, J Yepes, M Luo, HBR Ye, KQ AF Chan, Chi Bun Liu, Xia Pradoldej, Sompol Hao, Chunhai An, Jie Yepes, Manuel Luo, Hongbo R. Ye, Keqiang TI Phosphoinositide 3-Kinase Enhancer Regulates Neuronal Dendritogenesis and Survival in Neocortex SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MIDDLE CEREBRAL-ARTERY; LHERMITTE-DUCLOS-DISEASE; NEUROTROPHIC FACTOR; CELL-DEATH; DENDRITIC ARBORIZATION; TARGETED DISRUPTION; NUCLEAR GTPASE; NERVOUS-SYSTEM; SOMA SIZE; RAT-BRAIN AB Phosphoinositide 3-kinase enhancer (PIKE) binds and enhances phosphatidylinositol 3-kinase (PI3K)/Akt activities. However, its physiological functions in brain have never been explored. Here we show that PIKE is important in regulating the neuronal survival and development of neocortex. During development, enhanced apoptosis is observed in the ventricular zone of PIKE knock-out (PIKE(-/-)) cortex. Moreover, PIKE(-/-) neurons show reduced dendritic complexity, dendritic branch length, and soma size. These defects are due to the reduced PI3K/Akt activities in PIKE(-/-) neurons, as the impaired dendritic arborization can be rescued when PI3K/Akt cascade is augmented in vitro or in PIKE(-/-) PTEN(-/-) double-knock-out mice. Interestingly, PIKE(-/-) mice display behavioral abnormality in locomotion and spatial navigation. Because of the diminished PI3K/Akt activities, PIKE(-/-) neurons are more vulnerable to glutamate- or stroke-induced neuronal cell death. Together, our data established the critical role of PIKE in regulating neuronal survival and development by substantiating the PI3K/Akt pathway. C1 [Chan, Chi Bun; Liu, Xia; Pradoldej, Sompol; Hao, Chunhai; Ye, Keqiang] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [An, Jie; Yepes, Manuel] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [An, Jie; Yepes, Manuel] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Atlanta, GA 30322 USA. [Luo, Hongbo R.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Dept Pathol, Boston, MA 02215 USA. [Luo, Hongbo R.] Childrens Hosp Boston, Dept Lab Med, Boston, MA 02215 USA. RP Ye, KQ (reprint author), Emory Univ, Sch Med, Dept Pathol & Lab Med, 615 Michael St, Atlanta, GA 30322 USA. EM kye@emory.edu RI Yepes, Manuel/C-3576-2011 FU NIH [R01 (NS45627), R01 (NS49478)] FX This work is supported by NIH Grants R01 (NS45627) to K.Y. and R01 (NS49478) to M.Y. We thank the Rodent Behavioral Core Facility of Emory University for performing the Morris water maze and Y-maze, and the Histology and EM Laboratory of Yerkes National Primate Research Center, Emory University for the preparation of the tissue sections. NR 48 TC 33 Z9 33 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 1 PY 2011 VL 31 IS 22 BP 8083 EP 8092 DI 10.1523/JNEUROSCI.1129-11.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 772CJ UT WOS:000291208100015 PM 21632930 ER PT J AU Nelissen, K Vanduffel, W AF Nelissen, Koen Vanduffel, Wim TI Grasping-Related Functional Magnetic Resonance Imaging Brain Responses in the Macaque Monkey SO JOURNAL OF NEUROSCIENCE LA English DT Article ID POSTERIOR PARIETAL CORTEX; VENTRAL PREMOTOR CORTEX; MEDIAL PARIETOOCCIPITAL CORTEX; CORTICAL MOTOR SYSTEM; AREA V6A; VISUAL GUIDANCE; SOMATOTOPIC ORGANIZATION; OBJECT RECOGNITION; ONLINE ADJUSTMENTS; LATERAL SULCUS AB Research in recent decades has suggested the existence of a dedicated brain network devoted to the organization and execution of grasping, one of the most important and skilled movements of primates. Grasping an object requires the transformation of intrinsic object properties such as size, orientation, and shape into an appropriate motor scheme shaping the hand. Although electrophysiological recordings in the monkey model have proven invaluable for gaining insights into the neuronal substrate underlying this complex behavior, knowledge concerning the existence and organization of a similar system in the human brain is derived mainly from imaging studies. Here, we present for the first time functional magnetic resonance imaging (fMRI) of brain activity while macaque monkeys performed reaching and grasping movements in a 3 tesla MR scanner. Grasping in the dark (compared with reaching) yielded significant activations in anterior intraparietal area and ventral premotor area F5, in addition to area PFG in the rostral inferior parietal lobule, somatosensory areas (SI, SII, area 5), and the hand field of F1. Whole-brain macaque fMRI motor studies will be instrumental in establishing possible homologies concerning grasping organization in the human and monkey brains, bridging the gap between human imaging and monkey electrophysiology. C1 [Nelissen, Koen; Vanduffel, Wim] Katholieke Univ Leuven, Sch Med, Lab Neuro & Psychofysiol, B-3000 Louvain, Belgium. [Nelissen, Koen; Vanduffel, Wim] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Nelissen, K (reprint author), Katholieke Univ Leuven, Sch Med, Lab Neuro & Psychofysiol, Herestr 49,Bus 1021,O&N2 Campus Gasthuisberg, B-3000 Louvain, Belgium. EM koen.nelissen@med.kuleuven.be FU Queen Elisabeth Foundation [10/008]; Interuniversity Attraction Pole [6/29]; Geconcerteerde Onderzoeksactie [10/19]; Hercules II funds; Fonds Wetenschappelijk Onderzoek (FWO) Vlaanderen [G.0.622.08, G.0.593.09]; National Institute of Neurological Disorders and Stroke [1R21 NS064432]; National Science Foundation [BCS-0745436] FX This work was supported by the Queen Elisabeth Foundation, Program Financing/10/008, Interuniversity Attraction Pole 6/29, Geconcerteerde Onderzoeksactie/10/19, Hercules II funds, Fonds Wetenschappelijk Onderzoek (FWO) Vlaanderen G.0.622.08 and G.0.593.09, National Institute of Neurological Disorders and Stroke Grant 1R21 NS064432, and National Science Foundation Grant BCS-0745436. K.N. is a postdoctoral research fellow of the FWO. We thank A. Coeman, W. Depuydt, M. De Paep, M. Docx, C. Fransen, P. Kayenbergh, Dr. H. Kolster, G. Meulemans, Dr. R. Peeters, I. Puttemans, C. Van Eupen, and S. Verstraeten for technical assistance, Dr. D. Stoianovici from Johns Hopkins Medicine for providing the Pneustep MR-compatible motor, and Drs. G. Luppino and S. Raiguel for valuable comments on this manuscript. NR 90 TC 36 Z9 36 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 1 PY 2011 VL 31 IS 22 BP 8220 EP 8229 DI 10.1523/JNEUROSCI.0623-11.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 772CJ UT WOS:000291208100028 PM 21632943 ER PT J AU Spiliopoulos, K Williams, Z AF Spiliopoulos, Konstantinos Williams, Ziv TI Peripheral nerve injury Response SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID BRACHIAL-PLEXUS C1 [Spiliopoulos, Konstantinos; Williams, Ziv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. RP Spiliopoulos, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. NR 3 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 JUN PY 2011 VL 114 IS 6 BP 1519 EP 1519 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 770YB UT WOS:000291123300008 ER PT J AU Stufflebeam, SM Liu, HS Sepulcre, J Tanaka, N Buckner, RL Madsen, JR AF Stufflebeam, Steven M. Liu, Hesheng Sepulcre, Jorge Tanaka, Naoaki Buckner, Randy L. Madsen, Joseph R. TI Epileptic foci Response SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material C1 [Stufflebeam, Steven M.; Liu, Hesheng; Sepulcre, Jorge; Tanaka, Naoaki; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sepulcre, Jorge; Madsen, Joseph R.] Harvard Univ, Ctr Brain Sci, Dept Psychol, Cambridge, MA 02138 USA. [Sepulcre, Jorge; Buckner, Randy L.] Howard Hughes Med Inst, Cambridge, MA USA. [Madsen, Joseph R.] Childrens Hosp, Boston, MA 02115 USA. [Stufflebeam, Steven M.; Buckner, Randy L.; Madsen, Joseph R.] Harvard Univ, Sch Med, Boston, MA USA. RP Stufflebeam, SM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 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 JUN PY 2011 VL 114 IS 6 BP 1692 EP 1692 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 770YB UT WOS:000291123300036 ER PT J AU Stufflebeam, SM Liu, HS Sepulcre, J Tanaka, N Buckner, RL Madsen, JR AF Stufflebeam, Steven M. Liu, Hesheng Sepulcre, Jorge Tanaka, Naoaki Buckner, Randy L. Madsen, Joseph R. TI Localization of focal epileptic discharges using functional connectivity magnetic resonance imaging SO JOURNAL OF NEUROSURGERY LA English DT Article DE functional MR imaging; epilepsy; interictal discharges; functional connectivity MR imaging; localization; noninvasive localization ID SPONTANEOUS FLUCTUATIONS; ALZHEIMERS-DISEASE; BRAIN ACTIVITY; EEG; MRI; SEIZURES; NETWORKS; SURGERY; FMRI; HUBS AB Object. In patients with medically refractory epilepsy the accurate localization of the seizure onset zone is critical for successful surgical treatment. The object of this study was to investigate whether the degree of coupling of spontaneous brain activity as measured with functional connectivity MR imaging (fcMR imaging) can accurately identify and localize epileptic discharges. Methods. The authors studied 6 patients who underwent fcMR imaging presurgical mapping and subsequently underwent invasive electroencephalography. Results. Focal regions of statistically significant increases in connectivity were identified in 5 patients when compared with an ad hoc normative sample of 300 controls. The foci identified by fcMR imaging overlapped the epileptogenic areas identified by in encephalography in all 5 patients. Conclusions. These results suggest that fcMR imaging may provide an effective high spatial resolution and noninvasive method of localizing epileptic discharges in patients with refractory epilepsy. (DOI: 10.3171/2011.1.JNS10482) C1 [Stufflebeam, Steven M.; Liu, Hesheng; Sepulcre, Jorge; Tanaka, Naoaki; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Stufflebeam, Steven M.; Buckner, Randy L.; Madsen, Joseph R.] Harvard Univ, Sch Med, Boston, MA USA. [Sepulcre, Jorge; Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Madsen, Joseph R.] Childrens Hosp, Boston, MA 02115 USA. RP Stufflebeam, SM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St Mail Code 2301, Charlestown, MA USA. EM sms@nmr.mgh.harvard.edu FU National Institute on Aging [AG021910]; National Center for Research Resources [P41RR14074]; National Institute of Mental Health [K08MH067966]; Harvard Catalyst Pilot; Howard Hughes Medical Institute FX This work was supported by National Institute on Aging Grant AG021910, National Center for Research Resources Grant P41RR14074, National Institute of Mental Health Grant K08MH067966, a Harvard Catalyst Pilot Grant, and the Howard Hughes Medical Institute. NR 29 TC 39 Z9 40 U1 1 U2 1 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 JUN PY 2011 VL 114 IS 6 BP 1693 EP 1697 DI 10.3171/2011.1.JNS10482 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 770YB UT WOS:000291123300037 PM 21351832 ER PT J AU Natarajan, SK Dandona, P Karmon, Y Yoo, AJ Kalia, JS Hao, Q Hsu, DP Hopkins, LN Fiorella, DJ Bendok, BR Nguyen, TN Rymer, MM Nanda, A Liebeskind, DS Zaidat, OO Nogueira, RG Siddiqui, AH Levy, EI AF Natarajan, Sabareesh K. Dandona, Paresh Karmon, Yuval Yoo, Albert J. Kalia, Junaid S. Hao, Qing Hsu, Daniel P. Hopkins, L. Nelson Fiorella, David J. Bendok, Bernard R. Nguyen, Thanh N. Rymer, Marilyn M. Nanda, Ashish Liebeskind, David S. Zaidat, Osama O. Nogueira, Raul G. Siddiqui, Adnan H. Levy, Elad I. TI Prediction of adverse outcomes by blood glucose level after endovascular therapy for acute ischemic stroke SO JOURNAL OF NEUROSURGERY LA English DT Article DE admission blood glucose; acute ischemic stroke; change in blood glucose at 48 hours; endovascular therapy; prognostic scale; vascular disorder ID ACUTE MYOCARDIAL-INFARCTION; FOCAL CEREBRAL-ISCHEMIA; ADMISSION HYPERGLYCEMIA; POSTSTROKE HYPERGLYCEMIA; BRAIN-DAMAGE; MERCI TRIAL; INSULIN; MANAGEMENT; MORTALITY; REMOVAL AB Object. The authors evaluated the prognostic significance of blood glucose level at admission (BOA) and change in blood glucose at 48 hours from the baseline value (CG48) in nondiabetic and diabetic patients before and after endovascular therapy for acute ischemie stroke (AIS). Methods. The BOA and CG48 data were analyzed in 614 patients with AIS who received endovascular therapy at 7 US centers between 2006 and 2009. Data reviewed included demographics, stroke risk factors, diabetic status. National Institutes of Health Stroke Scale (NIHSS) score at presentation. recanalization grade. intracranial hemorrhage (ICH) rate, and 90-day outcomes (mortality rate and modified Rankin Scale score of 3-6 [defined as poor outcome]). Variables with p values < 0.2 in univariate analysis were included in a binary logistic regression model for independent predictors of 90-day outcomes. Results. The mean patient age was 67.3 years. the median NIHSS score was 16, and 27% of patients had diabetes. In nondiabetic patients. BGA >= 116 mg/dl (>= 6.4 mmol/L) and failure of glucose level to drop > 30 mg/dl (> 1.7 mmol/L) from the admission value were both significant predictors of 90-day poor outcome and death (p < 0.001). In patients with diabetes. BGA >= 116 mg/dl (>= 6.4 mmol/L) was an independent predictor of poor outcome (p = 0.001). The CG48 was not a predictor of outcome in diabetic patients. A simplified 6-point scale including BGA. Thrombolysis in Myocardial Infarction (TIMI) Grade 2-3 Reperfusion. Age. presentation NIHSS score, CG48. and symptomatic ICH (BRANCH) corresponded with poor outcomes at 90 days: the area under the curve value was > 0.79. Conclusions. Failure of blood glucose values to decrease in the first 48 hours after AIS intervention correlated with poor 90-day outcomes in nondiabetic patients. The BRANCH scale shows promise as a simple prognostication tool after endovascular therapy for AIS. and it merits prospective validation. (DOI: 10.3171/2011.LINS10884) C1 [Natarajan, Sabareesh K.; Dandona, Paresh; Karmon, Yuval; Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Buffalo, NY 14209 USA. [Fiorella, David J.] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. [Yoo, Albert J.; Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nguyen, Thanh N.] Boston Univ, Boston, MA 02215 USA. [Kalia, Junaid S.; Zaidat, Osama O.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Hao, Qing; Liebeskind, David S.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Hsu, Daniel P.; Nanda, Ashish] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Bendok, Bernard R.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Rymer, Marilyn M.] St Lukes Brain & Stroke Inst, Kansas City, MO USA. RP Levy, EI (reprint author), SUNY Buffalo, 3 Gates Circle, Buffalo, NY 14209 USA. EM elevy@ubns.com OI Kalia, Junaid/0000-0001-7121-8638 NR 32 TC 10 Z9 11 U1 0 U2 2 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 JUN PY 2011 VL 114 IS 6 BP 1785 EP 1799 DI 10.3171/2011.1.JNS10884 PG 15 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 770YB UT WOS:000291123300053 PM 21351835 ER PT J AU Ferreira, M Walcott, BP Nahed, BV Sekhar, LN AF Ferreira, Manuel, Jr. Walcott, Brian P. Nahed, Brian V. Sekhar, Laligam N. TI Vertebral artery pexy for microvascular decompression of the facial nerve in the treatment of hemifacial spasm SO JOURNAL OF NEUROSURGERY LA English DT Article DE hemifacial spasm; microvascular decompression; vertebral artery; brainstem; facial nerve; cranial nerve VII; pledget ID TRIGEMINAL NEURALGIA; TECHNICAL NOTE; COMPRESSION; PATTERNS AB Object. Hemi facial spasm (HFS) is caused by arterial or venous compression of cranial nerve VII at its root exit zone. Traditionally, microvascular decompression of the facial nerve has been an effective treatment for posterior inferior and anterior inferior cerebellar artery as well as venous compression. The traditional technique involves Teflon felt or another construct to cushion the offending vessel from the facial nerve, or cautery and division of the offending vein. However, using this technique for severe vertebral artery (VA) compression can he ineffective and fraught with complications. The authors report the use of a new technique of VA pexy to the petrous or clival dura mater in patients with HFS attributed to a severely ectatic and tortuous VA. and detail the results in a series of patients. Methods. Six patients with I-IFS due to VA compression underwent a retrosigmoid craniotomy. combined with a far-lateral approach in some patients. On identification of the site of VA compression. the vessel was mobilized adequately for the decompression. Great care was taken to avoid kinking the perforating vessels arising from the VA. Two 8-0 nylon sutures were passed through to the wall of the VA and then through the diva! or petrous dura, and then tied to alleviate compression on cranial nerve VII. Results. Patients were followed for at least 1 year postoperatively (mean 2.7 years. range 1 4 years). All 6 patients had complete resolution of their HFS. Facial function was tested postoperatively. and was stable when compared with the preoperative baseline. Two of the 3 patients with preoperative Minims had resolution of this symptom after the procedure. Postoperative imaging demonstrated VA decompression of the facial nerve and no evidence of stroke in all patients. One patient suffered from hearing loss, another developed a postoperative transient unilateral vocal cord paralysis, and a third patient developed a pseudomeningocele that resolved with the placement of a lumbar drain. Conclusions. Hemifacial spasm and other neurovascular syndromes are effectively treated by repositioning the compressing artery. Careful study of the preoperative MR images may identify a select group of patients with I-IFS due to an ectatic VA. Rather than traditional decompression with only pledget placement, these patients may be from a VA pexy to provide an effective. safe. and durable resolution of their symptoms while minimizing surgical complications. (DOI: 10.3171/2010.12.INS10891) C1 [Sekhar, Laligam N.] Univ Washington, Harborview Med Ctr, Sch Med, Dept Neurosurg, Seattle, WA 98104 USA. [Walcott, Brian P.; Nahed, Brian V.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Nahed, Brian V.] Harvard Univ, Sch Med, Boston, MA USA. RP Sekhar, LN (reprint author), Univ Washington, Harborview Med Ctr, Sch Med, Dept Neurosurg, Box 359924,325 9th Ave, Seattle, WA 98104 USA. EM lsekhar@u.washington.edu NR 24 TC 7 Z9 13 U1 0 U2 2 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 JUN PY 2011 VL 114 IS 6 BP 1800 EP 1804 DI 10.3171/2010.12.JNS10891 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 770YB UT WOS:000291123300054 PM 21275561 ER PT J AU Stepp, CE Hillman, RE Heaton, JT AF Stepp, Cara E. Hillman, Robert E. Heaton, James T. TI Modulation of Neck Intermuscular Beta Coherence During Voice and Speech Production SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE voice; speech disorders; electromyography ID HIGH-FREQUENCY OSCILLATIONS; EEG-EMG; TENSION DYSPHONIA; MUSCLE; FRAMEWORK; SPEAKING; HUMANS; FORCES; CORTEX; TASK AB Purpose: The purpose of this study was to better understand neck intermuscular beta coherence (15-35 Hz; NIBcoh) in healthy individuals, with respect to modulation by behavioral tasks. Method: Mean NIBcoh was measured using surface electromyography at 2 anterior neck locations in 10 individuals during normal speech, static nonspeech maneuvers, "clear" speech (intentionally produced to maximize intelligibility), divided-attention speech, singing, and mimicked hyperfunctional speech. Results: An analysis of variance showed significant effects of both individual and condition (p = .001) on the mean beta-band intermuscular coherence. Dunnett's simultaneous paired t tests found decreased NIBcoh during low-attention speech, singing, and hyperfunctional speech (padj < .05), but no significant difference in NIBcoh during nonspeech tasks or clear speech production relative to normal speech. Conclusions: Compared with normal speech, mean NIBcoh was decreased in a divided-attention speech task, but clear speech did not result in increased mean coherence relative to normal speech, possibly due to ceiling effects caused by heightened attention and precision during experimental recording. Mimicking a strained, hyperfunctional voice resulted in a reduction in mean beta intermuscular coherence quantitatively and qualitatively similar to the lowered values of mean beta coherence seen in individuals with vocal nodules relative to individuals with normal voice. C1 [Stepp, Cara E.; Hillman, Robert E.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Stepp, Cara E.; Hillman, Robert E.; Heaton, James T.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Hillman, Robert E.; Heaton, James T.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Stepp, CE (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM cstepp@alum.mit.edu NR 31 TC 4 Z9 5 U1 2 U2 3 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD JUN 1 PY 2011 VL 54 IS 3 BP 836 EP 844 DI 10.1044/1092-4388(2010/10-0139) PG 9 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 771NM UT WOS:000291166100009 PM 21106697 ER PT J AU Goodman, M Siever, LJ AF Goodman, Marianne Siever, Larry J. TI Hypermentalization in Adolescents With Borderline Personality Traits: Extending the Conceptual Framework to Younger Ages SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID DISORDER C1 [Goodman, Marianne; Siever, Larry J.] Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Goodman, M (reprint author), Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Marianne.Goodman@va.gov NR 11 TC 2 Z9 2 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2011 VL 50 IS 6 BP 536 EP 537 DI 10.1016/j.jaac.2011.02.013 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 773DZ UT WOS:000291288500002 PM 21621135 ER PT J AU Wilens, TE Martelon, M Joshi, G Bateman, C Fried, R Petty, C Biederman, J AF Wilens, Timothy E. Martelon, MaryKate Joshi, Gagan Bateman, Clancey Fried, Ronna Petty, Carter Biederman, Joseph TI Does ADHD Predict Substance-Use Disorders? A 10-Year Follow-up Study of Young Adults With ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ADHD; substance-use disorders; longitudinal follow-up; conduct disorder ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DSM-III-R; DRUG-USE; PSYCHIATRIC STATUS; ALCOHOL-ABUSE; UNITED-STATES; CANNABIS USE; ADOLESCENT; RISK AB Objective: High rates of substance-use disorders (SUD) have been found in samples of adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Predictors of SUD in children with ADHD who are at risk for the development of SUDs remain understudied. The main aims of this study were to identify clinically meaningful characteristics of children that predicted the future development of SUDs and to see whether the role of these characteristics varied by sex. Method: Subjects were children and adolescents with (n = 268; mean age +/- standard deviation = 10.9 +/- 3.2 years) and without (n = 229; mean age 11.9 +/- 3.3 years) DSM-III-R ADHD followed prospectively and blindly over a 10-year follow-up period onto young adult years. Subjects were assessed with structured diagnostic interviews for psychopathology and SUDs. Results: Over the 10-year follow-up period, ADHD was found to be a significant predictor of any SUD (hazards ratio 1.47; 95% confidence interval 1.07-2.02; p = .01) and cigarette smoking (2.38; 1.61-3.53; p < .01). Within ADHD, comorbid conduct disorder (2.74; 1.66-4.52; p < .01) and oppositional defiant disorder (2.21; 1.40-3.51; p < .01) at baseline were also found to be significant predictors of SUDs. Similar results were found for cigarette-, alcohol-, and drug-use disorders. There were few meaningful sex interaction effects. No clinically significant associations were found for any social or family environment factors or for cognitive functioning factors (p > .05 for all comparisons). Conclusions: These results indicate that ADHD is a significant risk factor for the development of SUDs and cigarette smoking in both sexes. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(6):543-553. C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Clin & Res Program Pediat Psychopharmacol, 55 Parkman St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org RI Reis, Aline/G-9573-2012 FU United States Public Health Service (National Institute on Child Health and Human Development) [K24 DA016264]; Eli Lilly and Company Foundation [5R01 HD-36317-07]; Pediatric Psychopharmacology Philanthropy Fund; Abbott; McNeil; Eli Lilly and Co.; National Institutes of Health-National Institute on Drug Abuse; Nextwave; Merck; Shire; Guildford Press; Alza; AstraZeneca; Bristol Myers Squibb; Celltech; Cephalon; Elminda; Esai; Forest; GlaxoSmithKline; Gliatech; Janssen; Notional Alliance for Research on Schizophrenia and Depression; National Institute on Drug Abuse; New River; National Institute of Child Health and Human Development; National Institute of Mental Health; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma; Wyeth; Johnson and Johnson; Takeda; Ethel DuPont Fellowship Award; American Academy of Child and Adolescent Psychiatry FX This study was funded by grant K24 DA016264 (T.W.) and in part by a grant from the United States Public Health Service (National Institute on Child Health and Human Development) and by grant 5R01 HD-36317-07 (J.B.) and in part by a grant from the Eli Lilly and Company Foundation and the Pediatric Psychopharmacology Philanthropy Fund.; Dr. Wilens has received grant support from Abbott, McNeil, Eli Lilly and Co., the National Institutes of Health-National Institute on Drug Abuse, Nextwave, Merck, and Shire. He has served on the speakers' bureau for Eli Lilly and Co., McNeil, Novartis, and Shire. He has served as a consultant to Abbott, AstraZeneca, McNeil, Eli Lilly and Co., the National Institutes of Health, Nextwave, Novartis, Merck, and Shire. He receives royalties from Guildford Press. Dr. Biederman has received research support from Abbott, Alza, AstraZeneca, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Elminda, Esai, Forest, GlaxoSmithKline, Gliatech, Janssen, McNeil, Merck, the Notional Alliance for Research on Schizophrenia and Depression, the National Institute on Drug Abuse, New River, the National Institute of Child Health and Human Development, the National Institute of Mental Health, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, the Prechter Foundation, Shire, the Stanley Foundation, UCB Pharma, and Wyeth. He has served on the speakers' bureau for Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association. Dr. Joshi has received research support from Abbott, Bristol Myers Squibb, Cephalon, Eli Lilly and Co., GlaxoSmithKline, Johnson and Johnson, McNeil, Merck, the National Institute of Mental Health, New River, Novartis, Organon, Otsuka, Takeda, Pfizer, and Shire. He is a member of the National Institute of Mental Health Editorial Board. He has received the Ethel DuPont Fellowship Award. He has received the Pilot Research Award from the American Academy of Child and Adolescent Psychiatry. Ms. Marie Ion, Mr. Bateman, Ms. Fried, and Mr. Petty report no biomedical financial interests or potential conflicts of interest. NR 56 TC 82 Z9 83 U1 4 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2011 VL 50 IS 6 BP 543 EP 553 DI 10.1016/j.jaac.2011.01.021 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 773DZ UT WOS:000291288500005 PM 21621138 ER PT J AU Lovas, D AF Lovas, David TI Room SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Lovas, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lovas, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dlovas@partners.org NR 1 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2011 VL 50 IS 6 BP 624 EP 626 DI 10.1016/j.jaac.2011.04.006 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 773DZ UT WOS:000291288500015 ER PT J AU Farasat, S Yu, SS Neel, VA Nehal, KS Lardaro, T Mihm, MC Byrd, DR Balch, CM Califano, JA Chuang, AY Sharfman, WH Shah, JP Nghiem, P Otley, CC Thfaro, AP Johnson, TM Sober, AJ Liegeois, NJ AF Farasat, Sharifeh Yu, Siegrid S. Neel, Victor A. Nehal, Kishwer S. Lardaro, Thomas Mihm, Martin C. Byrd, David R. Balch, Charles M. Califano, Joseph A. Chuang, Alice Y. Sharfman, William H. Shah, Jatin P. Nghiem, Paul Otley, Clark C. Thfaro, Anthony P. Johnson, Timothy M. Sober, Arthur J. Liegeois, Nanette J. TI A new American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: Creation and rationale for inclusion of tumor (T) characteristics SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID NONMELANOMA SKIN-CANCER; ORGAN TRANSPLANT RECIPIENTS; LYMPH-NODE METASTASIS; PERINEURAL INVASION; PROGNOSTIC FACTORS; PAROTID-GLAND; HEAD; NECK; RISK; LIP AB Background: The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing. Although most patients achieve complete remission with surgical treatment, those with advanced disease have a poor prognosis. The American Joint Committee on Cancer (AJCC) is responsible for the staging criteria for all cancers. For the past 20 years, the AJCC cancer staging manual has grouped all nonmelanoma skin cancers, including cSCC, together for the purposes of staging. However, based on new evidence, the AJCC has determined that cSCC should have a separate staging system in the 7th edition AJCC staging manual. Objective: We sought to present the rationale for and characteristics of the new AJCC staging system specific to cSCC tumor characteristics (T). Methods: The Nonmelanoma Skin Cancer Task Force of AJCC reviewed relevant data and reached expert consensus in creating the 7th edition AJCC staging system for cSCC. Emphasis was placed on prospectively accumulated data and multivariate analyses. Concordance with head and neck cancer staging system was also achieved. Results: A new AJCC cSCC T classification is presented. The T classification is determined by tumor diameter, invasion into cranial bone, and high-risk features, including anatomic location, tumor thickness and level, differentiation, and perineural invasion. Limitations: The data available for analysis are still suboptimal, with limited prospective outcomes trials and few multivariate analyses. Conclusions: The new AJCC staging system for cSCC incorporates tumor-specific (T) staging features and will encourage coordinated, consistent collection of data that will be the basis of improved prognostic systems in the future. (J Am Acad Dermatol 2011;64:1051-9.) C1 [Farasat, Sharifeh; Lardaro, Thomas] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Balch, Charles M.] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. [Balch, Charles M.; Sharfman, William H.; Liegeois, Nanette J.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Balch, Charles M.; Chuang, Alice Y.; Sharfman, William H.] Johns Hopkins Univ, Dept Dermatol, Baltimore, MD 21218 USA. [Califano, Joseph A.; Liegeois, Nanette J.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21218 USA. [Thfaro, Anthony P.; Liegeois, Nanette J.] Johns Hopkins Univ, Dept Plast Surg, Baltimore, MD 21218 USA. [Yu, Siegrid S.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Neel, Victor A.; Sober, Arthur J.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Mihm, Martin C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Nehal, Kishwer S.] Mem Sloan Kettering Canc Ctr, Dermatol Serv, New York, NY 10021 USA. [Shah, Jatin P.] Mem Sloan Kettering Canc Ctr, Dept Surg, Head & Neck Serv, New York, NY 10021 USA. [Byrd, David R.] Univ Washington, Dept Surg, Div Plast Surg, Seattle, WA 98195 USA. [Nghiem, Paul] Univ Washington, Dept Med, Div Dermatol, Seattle, WA 98195 USA. [Otley, Clark C.] Mayo Clin, Div Dermatol Surg, Rochester, MN USA. [Johnson, Timothy M.] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. RP Liegeois, NJ (reprint author), Univ Maryland, Dept Dermatol, 419 W Redwood St,Suite 240, Baltimore, MD 21201 USA. EM NLiegeois@jhu.edu RI Nghiem, Paul/A-9210-2011; OI Nghiem, Paul/0000-0003-2784-963X; Shah, Jatin/0000-0002-6444-6592 FU Dermatology Foundation FX Dr Liegeois is supported with a Career Development Award from the Dermatology Foundation. NR 56 TC 79 Z9 79 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUN PY 2011 VL 64 IS 6 BP 1051 EP 1059 DI 10.1016/j.jaad.2010.08.033 PG 9 WC Dermatology SC Dermatology GA 770XD UT WOS:000291120900004 PM 21255868 ER PT J AU Lipworth, AD Park, JM Trefrey, BL Rubin, KM Geller, AC Sober, AJ Tsao, H AF Lipworth, Adam D. Park, Jong Min Trefrey, Brie L. Rubin, Krista M. Geller, Alan C. Sober, Arthur J. Tsao, Hensin TI Urgent access to a specialty care melanoma clinic is associated with a higher rate of melanoma detection SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE detection; melanoma; pigmented lesion; pigmented lesion clinic; routine visit; urgent access; urgent access track ID FOLLOW-UP GUIDELINES; LONG-TERM SURVIVAL; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; DERMATOLOGY; DIAGNOSIS; STAGE; TELEDERMATOLOGY; METASTASES; SYSTEM AB Background: As melanoma rates increase, and the supply of dermatologists remains suboptimal to meet demand for services, detection of early melanoma has become an increasingly difficult challenge. Some authors advocate for shifting dermatologic resources from routine appointments to urgent visits for those With lesions concerning for melanoma. Objective: We sought to investigate the potential of an urgent access track (UAT) embedded within a pigmented lesion clinic to improve early melanoma detection. Methods: We conducted a retrospective review of patient records from a tertiary care hospital's pigmented lesion clinic and the associated UAT. Results of procedures for all 4495 patient visits to the routine track and all 316 visits to the UAT during the 21-month study period were included, as were detailed chart reviews of all UAT patient visits. Results: UAT visits were more than 4 times as likely (4.1% vs 1.0%) to yield a diagnosis of melanoma as routine track visits (odds ratio 4.24; 95% confidence interval 2.28-7.88; P < .0001), and almost 25 times as likely (2.2% vs 0.1%) to yield a diagnosis of metastatic melanoma (odds ratio 25.4; 95% confidence interval 7.4-87.4; P < .0001). Limitations: This was a preliminary analysis with only limited data extracted from the routine track pigmented lesion clinic patient visits. Conclusion: This initial analysis of UAT strategy suggests that UATs have potential to detect patients with earlier melanomas; further research is needed to specifically delineate how resources should be best allocated between routine surveillance and urgent care to maximize melanoma early detection and survival. (J Am Acad Dermatol 2011;64: 1060-7.) C1 [Lipworth, Adam D.; Trefrey, Brie L.; Sober, Arthur J.; Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Park, Jong Min; Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Trefrey, Brie L.; Rubin, Krista M.; Sober, Arthur J.; Tsao, Hensin] Massachusetts Gen Hosp, Melanoma & Pigmented Lesion Ctr, Ctr Canc, Boston, MA 02114 USA. [Geller, Alan C.] Harvard Univ, Div Publ Hlth Practice, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org NR 28 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUN PY 2011 VL 64 IS 6 BP 1060 EP 1067 DI 10.1016/j.jaad.2010.08.021 PG 8 WC Dermatology SC Dermatology GA 770XD UT WOS:000291120900005 PM 21453985 ER PT J AU Ibrahimi, OA Syed, Z Sakamoto, FH Avram, MM Anderson, RR AF Ibrahimi, Omar A. Syed, Zain Sakamoto, Fernanda H. Avram, Mathew M. Anderson, R. Rox TI Treatment of tattoo allergy with ablative fractional resurfacing: A novel paradigm for tattoo removal SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE laser therapy; Q-switchecl lasers; tattoo allergy ID Q-SWITCHED RUBY; ND-YAG LASER; DOSE-RESPONSE; NM; PHOTOTHERMOLYSIS AB Background: Q-switched lasers are the gold standard for tattoo treatment. Allergic tattoo reactions present a treatment dilemma. We present the application of ablative fractional resurfacing (AFR) as a novel method for tattoo removal. Objective: We describe two patients with tattoo allergies, referred to us for treatment. Methods: AFR was used in a series of treatments to remove the allergic-ink portion of a multicolored tattoo on the upper extremity of a 52-year-old man. In a 31-year-old woman with a red and black tattoo on her lower extremity, AFR was combined with a Q-switched neodymium:yttrium-aluminum-garnet laser. Results: After a series of treatments, both patients experienced significant to complete removal of the offending tattoo inks with substantial or complete resolution of their symptoms. Limitations: This uncontrolled observational series is based on two patients. Conclusions: AFR appears to be safe and effective for removal of allergic tattoos. AFR can be combined with other treatments such as Q-switched lasers. The potential for a series of AFR treatments to remove tattoos, including allergic tattoos and inks of any color, merits further study. (J Am Acad Dermatol 201164:1111-4.) C1 [Ibrahimi, Omar A.] Univ Connecticut, Dept Dermatol, Farmington, CT 06032 USA. [Ibrahimi, Omar A.; Sakamoto, Fernanda H.; Avram, Mathew M.; Anderson, R. Rox] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Ibrahimi, Omar A.; Sakamoto, Fernanda H.; Avram, Mathew M.; Anderson, R. Rox] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Syed, Zain] Univ Virginia, Charlottesville, VA 22903 USA. RP Ibrahimi, OA (reprint author), Univ Connecticut, Dept Dermatol, 21 South Rd, Farmington, CT 06032 USA. EM omar.ibrahimi@gmail.com NR 14 TC 24 Z9 24 U1 2 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUN PY 2011 VL 64 IS 6 BP 1111 EP 1114 DI 10.1016/j.jaad.2010.11.005 PG 4 WC Dermatology SC Dermatology GA 770XD UT WOS:000291120900011 PM 21571169 ER PT J AU Kim, JM Mudgal, CS Konopka, JF Jupiter, JB AF Kim, Jaehon M. Mudgal, Chaitanya S. Konopka, Joseph F. Jupiter, Jesse B. TI Complications of Total Elbow Arthroplasty SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID RHEUMATOID-ARTHRITIS; MORREY PROSTHESIS; SURVIVAL ANALYSIS; REPLACEMENT; REVISION; INFECTION; FRACTURES; COMPONENT; KINEMATICS; EXPERIENCE AB Modifications in implant design and improvements in surgical technique have expanded the applications of total elbow arthroplasty. Complications associated with reconstructive elbow surgery persist, however, often leading to profound and sometimes nonsalvageable disability. The most recognized complications include implant loosening, periprosthetic fracture, implant failure, infection, triceps insufficiency, and nerve palsy. Although far fewer elbow arthroplasties than lower extremity arthroplasties are performed, the proportion of complications is greater with elbow arthroplasty, and the outcomes of secondary reconstruction are less favorable. C1 [Kim, Jaehon M.; Konopka, Joseph F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Combined Orthopaed Residency Program, Boston, MA 02115 USA. [Mudgal, Chaitanya S.; Jupiter, Jesse B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. RP Kim, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Combined Orthopaed Residency Program, Boston, MA 02115 USA. NR 52 TC 29 Z9 29 U1 1 U2 1 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD JUN PY 2011 VL 19 IS 6 BP 328 EP 339 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 774FL UT WOS:000291370400003 PM 21628644 ER PT J AU Pfister, DG Ang, KK Brizel, DM Burtness, BA Cmelak, AJ Colevas, D Dunphy, F Eisele, DW Gilbert, J Gillison, ML Haddad, RI Haughey, BH Hicks, WL Hitchcock, YJ Kies, MS Lydiatt, WM Maghami, E Martins, R McCaffrey, T Mittal, BB Pinto, HA Ridge, JA Samant, S Sanguineti, G Schuller, DE Shah, JP Spencer, S Trotti, A Weber, RS Wolf, GT Worden, F AF Pfister, David G. Ang, Kie-Kian Brizel, David M. Burtness, Barbara A. Cmelak, Anthony J. Colevas, Dimitrios Dunphy, Frank Eisele, David W. Gilbert, Jill Gillison, Maura L. Haddad, Robert I. Haughey, Bruce H. Hicks, Wesley L., Jr. Hitchcock, Ying J. Kies, Merrill S. Lydiatt, William M. Maghami, Ellie Martins, Renato McCaffrey, Thomas Mittal, Bharat B. Pinto, Harlan A. Ridge, John A. Samant, Sandeep Sanguineti, Giuseppe Schuller, David E. Shah, Jatin P. Spencer, Sharon Trotti, Andy, III Weber, Randal S. Wolf, Gregory T. Worden, Frank TI Head and Neck Cancers SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; head and neck cancer; chemotherapy; radiotherapy; surgery; oral cavity; oropharynx; hypopharynx; nasopharynx; glottic; supraglottic; larynx ID SQUAMOUS-CELL CARCINOMA; LOCALLY ADVANCED HEAD; INTENSITY-MODULATED RADIOTHERAPY; COOPERATIVE-ONCOLOGY-GROUP; QUALITY-OF-LIFE; METASTATIC NASOPHARYNGEAL CARCINOMA; PROSPECTIVE RANDOMIZED-TRIAL; CISPLATIN PLUS FLUOROURACIL; ADVANCED LARYNGEAL-CANCER; PHASE-III TRIAL C1 [Pfister, David G.; Shah, Jatin P.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ang, Kie-Kian; Kies, Merrill S.; Weber, Randal S.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Cmelak, Anthony J.; Gilbert, Jill] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Colevas, Dimitrios; Pinto, Harlan A.] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Gillison, Maura L.; Schuller, David E.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Gillison, Maura L.; Schuller, David E.] Ohio State Univ, Ctr Comprehens Canc, Solove Res Inst, Columbus, OH 43210 USA. [Haddad, Robert I.] Dana Farber Brigham & Womens Canc, Boston, MA USA. [Haughey, Bruce H.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Haughey, Bruce H.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Hicks, Wesley L., Jr.] Roswell Pk Canc Inst, Buffalo, NY USA. [Hitchcock, Ying J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Lydiatt, William M.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Maghami, Ellie] City Hope Comprehens Canc Ctr, Duarte, CA USA. [McCaffrey, Thomas; Trotti, Andy, III] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Mittal, Bharat B.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Samant, Sandeep] Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. [Sanguineti, Giuseppe] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Spencer, Sharon] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, W Midlands, England. [Wolf, Gregory T.; Worden, Frank] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Pfister, DG (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 205 TC 83 Z9 85 U1 0 U2 11 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 JUN PY 2011 VL 9 IS 6 BP 596 EP 649 PG 54 WC Oncology SC Oncology GA 773BN UT WOS:000291282100002 PM 21636536 ER PT J AU Macdonald, A Monson, CM Doron-Lamarca, S Resick, PA Palfai, TP AF Macdonald, Alexandra Monson, Candice M. Doron-Lamarca, Susan Resick, Patricia A. Palfai, Tibor P. TI Identifying Patterns of Symptom Change During a Randomized Controlled Trial of Cognitive Processing Therapy for Military-Related Posttraumatic Stress Disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID CONFIRMATORY FACTOR-ANALYSIS; ADMINISTERED PTSD SCALE; SEXUAL ASSAULT VICTIMS; MENTAL-HEALTH PROBLEMS; EXPOSURE THERAPY; BEHAVIOR THERAPY; PSYCHOTHERAPY; CLINICIAN; DIMENSIONALITY; AFGHANISTAN AB Cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) has been shown to reduce symptoms of PTSD in a veteran population. This study explored patterns of self-reported symptom change during CPT. Veterans (N = 60) with PTSD were randomized to receive CPT immediately or after 10 weeks. We hypothesized that those treated immediately would evidence initial symptom stability followed by decline compared with those who waited, whose PTSD symptoms would remain stable. The best model fit based on deviance statistics and Bayesian information criteria comparisons was one in which participants treated immediately showed more rapid initial decline followed by a slower rate of PTSD symptom improvement relative to those who waited, who showed a stable level of symptomatology. Findings suggest that CPT produces quick and maintained improvements in veterans. The effect sizes for change between those who received CPT immediately and those who waited were approximately medium sized. Implications of findings are discussed. C1 [Macdonald, Alexandra; Palfai, Tibor P.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Macdonald, Alexandra] VA Boston Healthcare Syst, Boston, MA USA. RP Macdonald, A (reprint author), VA Boston Healthcare Syst 116B, 150 S Huntington Ave, Jamaica Plain, MA USA. EM Alexandra.Macdonald@va.gov RI Schueter, nicos/A-3625-2014 NR 40 TC 14 Z9 14 U1 4 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2011 VL 24 IS 3 BP 268 EP 276 DI 10.1002/jts.20642 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 773ZF UT WOS:000291350300004 PM 21626572 ER PT J AU Levy, HC Conoscenti, LM Tillery, JF Dickstein, BD Litz, BT AF Levy, Hannah C. Conoscenti, Lauren M. Tillery, John F. Dickstein, Benjamin D. Litz, Brett T. TI Deployment Stressors and Outcomes Among Air Force Chaplains SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID RESILIENCE; TRAUMA; CARE; RISK; IRAQ AB Military chaplains are invaluable caregiver resources for service members. Little is known about how chaplains respond to the challenge of providing spiritual counsel in a warzone. In this exploratory study, 183 previously deployed Air Force chaplains completed an online survey assessing operational and counseling stress exposure, posttraumatic stress disorder (PTSD) symptoms, compassion fatigue, and posttraumatic growth. Despite reporting exposure to stressful counseling experiences, Air Force chaplains did not endorse high compassion fatigue. Rather, chaplains experienced positive psychological growth following exposure to stressful counseling experiences. However, 7.7% of Air Force chaplains reported clinically significant PTSD symptoms, suggesting that they are not immune to deployment-related mental health problems. Simultaneous regression analyses revealed that counseling stress exposure predicted compassion fatigue (beta = .20) and posttraumatic growth (beta = .24), suggesting that caretaking in theatre is stressful enough to spur positive psychological growth in chaplains. Consistent with findings from previous studies, hierarchical regression analyses revealed that operational stress exposure predicted PTSD symptom severity (beta = .33) while controlling for demographic variables. C1 [Levy, Hannah C.; Conoscenti, Lauren M.; Dickstein, Benjamin D.; Litz, Brett T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Tillery, John F.] AF Chaplains Corps Coll, Columbia, SC USA. [Dickstein, Benjamin D.; Litz, Brett T.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Levy, HC (reprint author), Concordia Univ, Dept Psychol, 7141 Sherbrooke St W,SP 244, Montreal, PQ H4B 1R6, Canada. EM ha_levy@live.concordia.ca NR 13 TC 3 Z9 3 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2011 VL 24 IS 3 BP 342 EP 346 DI 10.1002/jts.20646 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 773ZF UT WOS:000291350300013 PM 21567477 ER PT J AU Simpson, TL Comtois, KA Moore, SA Kaysen, D AF Simpson, Tracy L. Comtois, Katherine Anne Moore, Sally A. Kaysen, Debra TI Comparing the Diagnosis of PTSD When Assessing Worst Versus Multiple Traumatic Events in a Chronically Mentally Ill Sample SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; EFFECT SIZE; SCALE AB Despite interest in the nature of the traumatic event required to meet Criterion A for posttraumatic stress disorder (PTSD) as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994), little attention has been paid to the diagnostic ramifications of linking PTSD symptoms to a single traumatic event in the context of multiple trauma exposures. In this study, 67 dually diagnosed clients with at least 2 potential Criterion A traumatic events completed the Posttraumatic Stress Diagnostic Scale twice, in counterbalanced order: once regarding their worst event and once regarding all events. When responding regarding their worst trauma, 53.7% met probable PTSD criteria. This rose to 67.2% when considering all traumas. Although preliminary, these results suggest that linking PTSD symptoms to a single traumatic event excludes a meaningful number of cases who are otherwise indistinguishable based on symptom profile. C1 [Simpson, Tracy L.; Moore, Sally A.] VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. [Simpson, Tracy L.; Comtois, Katherine Anne; Moore, Sally A.; Kaysen, Debra] Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Simpson, TL (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv, 1660 S Columbian Way,116 WTRC, Seattle, WA 98108 USA. EM Tracy.Simpson@va.gov NR 10 TC 4 Z9 4 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2011 VL 24 IS 3 BP 361 EP 364 DI 10.1002/jts.20647 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 773ZF UT WOS:000291350300017 PM 21594901 ER PT J AU Hajj-Ali, RA Singhal, AB Benseler, S Molloy, E Calabrese, LH AF Hajj-Ali, Rula A. Singhal, Aneesh B. Benseler, Susanne Molloy, Eamonn Calabrese, Leonard H. TI Primary angiitis of the CNS SO LANCET NEUROLOGY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; CEREBRAL AMYLOID ANGIOPATHY; GRANULOMATOUS-ANGIITIS; VASOCONSTRICTION SYNDROMES; DIAGNOSTIC-CRITERIA; ISCHEMIC-STROKE; BRAIN BIOPSY; MASS LESION; VASCULITIS; ANGIOGRAPHY AB Meaningful progress in our understanding and clinical approach to primary angiitis of the CNS (PACNS) has been made in the past three decades. Increased recognition of PACNS and general advances in diagnosis of neurological disorders have led to an aggressive diagnostic approach and a proliferation of case reports providing enriched clinical and pathological descriptions. We have witnessed major advances not only in the diagnosis of PACNS but in the recognition of its mimics. Epidemiological, clinical, neuroradiagnostic, and laboratory findings have enhanced our diagnostic accuracy and recognition of PACNS mimics, however, many challenges to our understanding and management of the disease in children and adults remain. C1 [Calabrese, Leonard H.] Cleveland Clin, Dept Rheumat & Immunol Dis, Orthopaed & Rheumatol Inst, Cleveland, OH 44195 USA. [Singhal, Aneesh B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Benseler, Susanne] Univ Toronto, Hosp Sick Children, Div Rheumatol, Dept Paediat, Toronto, ON M5G 1X8, Canada. [Molloy, Eamonn] St Vincents Univ Hosp, Dublin 4, Ireland. RP Calabrese, LH (reprint author), Cleveland Clin, Dept Rheumat & Immunol Dis, Orthopaed & Rheumatol Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM calabrl@ccf.org FU RJ Fasenmyer educational Fund FX LHC and RHA receive funding from The RJ Fasenmyer educational Fund. We thank Elizabeth Kirchner for editing the manuscript. NR 74 TC 96 Z9 103 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD JUN PY 2011 VL 10 IS 6 BP 561 EP 572 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 774HK UT WOS:000291376100015 PM 21601163 ER PT J AU Franco, RA Dowdall, JR Bujold, K Amann, C Faquin, W Redmond, RW Kochevar, IE AF Franco, Ramon A. Dowdall, Jayme R. Bujold, Kenneth Amann, Christopher Faquin, William Redmond, Robert W. Kochevar, Irene E. TI Photochemical Repair of Vocal Fold Microflap Defects SO LARYNGOSCOPE LA English DT Article DE Vocal folds; microflap; Rose Bengal; wound healing; photochemical tissue bonding ID CORNEAL INCISIONS; SKIN; KERATODESMOS; PRESSURE; COUGH; LASER; MODEL AB Objectives: To bond vocal fold flaps using a sutureless, nonthermal laser-assisted method combining visible light and photosensitizing dyes to produce collagen crosslinks. Study Design: In the ex vivo study, epithelial incisions were created in sheep vocal folds. The concentration of the Rose Bengal, and the laser fluence were varied and studied. The in vivo canine study evaluated the thickness of the basement membrane zone, density and distribution of collagen, elastin, and fibroblasts at time zero, 2 weeks, and 8 weeks. Methods: Ex Vivo: Rose Bengal at concentrations between 0.5% and 1.0% was applied to the free margins of the incision and irradiated with an Nd:YAG laser at fluences varying from 150 to 600 J/cm(2). The bonding was considered positive when the incision could withstand air at 2 pounds per square inch (psi) from a distance of 3 cm. In Vivo: 0.75% Rose Bengal was applied to the microflap edges and irradiated with an Nd: YAG laser for 140 seconds (100 J/cm(2)). The control side was not irradiated. Results: Ex Vivo: Bonding was achieved with a minimum of 0.75% Rose Bengal and 300 J/cm(2). In Vivo: There was no difference in the amount of subepithelial reaction between the experimental and control sides at 8 weeks. Conclusions: Photochemical tissue bonding is effective at sealing vocal fold incisions and did not create long-term scarring of the vocal folds. Use of this technique may allow for more predictable healing after microflap resection and may reduce the need for postoperative voice rest. C1 [Franco, Ramon A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Laryngol,Dept Otol & Laryngol, Boston, MA USA. [Dowdall, Jayme R.] Wayne State Univ, Detroit, MI USA. [Bujold, Kenneth; Amann, Christopher; Redmond, Robert W.; Kochevar, Irene E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Faquin, William] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Eye & Ear Infirm,Dept Pathol, Boston, MA USA. RP Franco, RA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. EM ramonfranco@meei.harvard.edu FU Center for Integration of Medicine and Innovative Technology (CIMIT) FX This work was supported with a Center for Integration of Medicine and Innovative Technology (CIMIT) grant; no other financial disclosures for R. Franco, J. Dowdall, K. Bujold, C. Amann, or W. Faquin. NR 27 TC 11 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 2011 VL 121 IS 6 BP 1244 EP 1251 DI 10.1002/lary.21797 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 772TP UT WOS:000291259900021 PM 21480282 ER PT J AU Wu, WE Kirov, II Zhang, K Babb, JS Joo, CG Ratai, EM Gonzalez, RG Gonen, O AF Wu, William E. Kirov, Ivan I. Zhang, Ke Babb, James S. Joo, Chan-Gyu Ratai, Eva-Maria Gonzalez, R. Gilberto Gonen, Oded TI Cross-Sectional and Longitudinal Reproducibility of Rhesus Macaque Brain Metabolites: A Proton MR Spectroscopy Study at 3 T SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE animal models; brain; MR spectroscopy; longitudinal metabolites concentration; rhesus macaque; reproducibility ID MAGNETIC-RESONANCE-SPECTROSCOPY; IN-VIVO; NEURONAL INJURY; CYNOMOLGUS MONKEYS; N-ACETYLASPARTATE; RELAXATION-TIMES; BASE-LINE; MODEL; REVEALS; T-2 AB Non-human primates are often used as preclinical model systems for (mostly diffuse or multi-focal) neurological disorders and their experimental treatment. Due to cost considerations, such studies frequently utilize non-destructive imaging modalities, MRI and proton MR spectroscopy ((1)H MRS). Cost may explain why the inter-and intra-animal reproducibility of the (1)H MRS observed brain metabolites, are not reported. To this end, we performed test-retest three-dimensional brain (1)H MRS in five healthy rhesus macaques at 3 T. Spectra were acquired from 224 isotropic (0.5 cm)(3) 5 125 mu L voxels, over 28 cm(3) (similar to 35%) of the brain, then individually phased, frequency aligned and summed into a spectrum representative of the entire volume of interest. This dramatically increases the metabolites' signal-to-noise ratios, while maintaining the (narrow) voxel linewidth. The results show that the average N-acetylaspartate, creatine, choline, and myo-inositol concentrations in the macaque brain are: 7.7 +/- 0.5, 7.0 +/- 0.5, 1.2 +/- 0.1 and 4.0 +/- 0.6 mM/g wet weight (mean +/- standard deviation). Their inter-animal coefficients of variation (CV) are 4%, 4%, 6%, and 15%; and the longitudinal (intra-animal) CVs are lower still: 4%, 5%, 5%, and 4%, much better than the 22%, 33%, 36%, and 45% intra-voxel CVs, demonstrating the advantage of the approach and its utility for preclinical studies of diffuse neurological diseases in rhesus macaques. Magn Reson Med 65:1522-1531, 2011. (C)2011 Wiley-Liss, Inc. C1 [Wu, William E.; Kirov, Ivan I.; Zhang, Ke; Babb, James S.; Gonen, Oded] NYU, Sch Med, Dept Radiol, New York, NY 10016 USA. [Joo, Chan-Gyu; Ratai, Eva-Maria; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Athinoula A 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 Wu, William/0000-0003-0990-4164; Kirov, Ivan/0000-0001-5641-8578; Gonen, Oded/0000-0002-3148-2028 FU NIH [EB01015, NS050520, NS050041, NS040237, NS059331]; National Center for Research Resources [P41RR14075] FX Grant sponsor: NIH; Grant numbers: EB01015, NS050520, NS050041, NS040237, NS059331; Grant sponsor: National Center for Research Resources; Grant number: P41RR14075. NR 42 TC 5 Z9 5 U1 0 U2 2 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 JUN PY 2011 VL 65 IS 6 BP 1522 EP 1531 DI 10.1002/mrm.22867 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 770VB UT WOS:000291115500003 PM 21337426 ER PT J AU Peng, Q Zhang, Y Nateras, OSE van Osch, MJP Duong, TQ AF Peng, Qi Zhang, Yi Nateras, Oscar San Emeterio van Osch, Matthias J. P. Duong, Timothy Q. TI MRI of Blood Flow of the Human Retina SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE ASL; retinal vessels; choroids; high-resolution MRI; hypercapnia ID CARBON-DIOXIDE; FUNCTIONAL MRI; OXYGEN; INVERSION; BRAIN; RATS; DEGENERATION; HYPERCAPNIA; RELAXATION; EFFICIENCY AB This study reports a high-resolution MRI approach to image basal blood flow and hypercapnia-induced blood-flow changes in the unanesthetized human retina on a 3-T MRI scanner. Pseudo-continuous arterial spin labeling technique with static tissue suppression was implemented to minimize movement artifacts and improve blood-flow sensitivity. Turbo spin-echo acquisition was used to achieve high spatial resolution free of susceptibility artifacts. The size, shape, and position of a custom-made receive radiofrequency coil were optimized for sensitivity in the posterior retina. Synchronized eye blink and respiration to the end of each data readout minimized eye movement and physiological fluctuation. Robust high-contrast blood-flow MRI of the unanesthetized human retina was obtained at 500 X 800 mu m(2) in-plane resolution. Blood flow in the posterior retina was 93 +/- 31 mL/(100 mL min) (mean +/- standard deviation, N = 5). Hypercapnic inhalation (5% CO(2)) increased blood flow by 12 +/- 4% relative to air (P < 0.01, N = 5). This study demonstrates the feasibility of blood-flow MRI of the retina of unanesthetized human. Because blood flow is tightly coupled to metabolic function under normal conditions and it is often perturbed in diseases, this approach could provide unique insights into retinal physiology and serve as an objective imaging biomarker for disease staging and testing of novel therapeutic strategies. This approach could open up new avenue of retinal research. Magn Reson Med 65:1768-1775, 2011. (C)2011 Wiley-Liss, Inc. C1 [Peng, Qi; Zhang, Yi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Peng, Qi; Zhang, Yi; Nateras, Oscar San Emeterio; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [van Osch, Matthias J. P.] Leiden Univ, Med Ctr, Dept Radiol, CJ Gorter Ctr High Field MRI, Leiden, Netherlands. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU Clinical Translational Science Award Pilot Grant, Translational Technology Resource Grant [UL1RR025767]; NIH/NEI [R01 EY014211, EY018855]; Department of Veterans Affairs FX Grant sponsors: Clinical Translational Science Award Pilot Grant, Translational Technology Resource Grant to TQD (Parent; Grant number: UL1RR025767); Grant sponsor: NIH/NEI; Grant numbers: R01 EY014211, EY018855 to TQD; Grant sponsor: Department of Veterans Affairs (VISN7 Career Development Award and MERIT to TQD). NR 45 TC 23 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUN PY 2011 VL 65 IS 6 BP 1768 EP 1775 DI 10.1002/mrm.22763 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 770VB UT WOS:000291115500028 PM 21590806 ER PT J AU Vanti, C Bonfiglioli, R Calabrese, M Marinelli, F Guccione, A Violante, FS Pillastrini, P AF Vanti, Carla Bonfiglioli, Roberta Calabrese, Monica Marinelli, Francesco Guccione, Andrew Violante, Francesco Saverio Pillastrini, Paolo TI Upper limb neurodynamic test 1 and symptoms reproduction in carpal tunnel syndrome. A validity study SO MANUAL THERAPY LA English DT Article DE Neurological examination; Reproducibility of the results; Carpal tunnel syndrome ID MEDIAN NERVE; PHYSICAL-EXAMINATION; PRACTICE PARAMETER; IN-VIVO; COMPRESSION; DIAGNOSIS; CONDUCTION; TENSION; CLASSIFICATION; LOCALIZATION AB The aim of this study was to estimate the validity of the Upper Limb Neurodynamic Test 1 (ULNT1) for the diagnosis of Carpal Tunnel Syndrome (CTS) with blind comparison to a reference criterion of a compatible clinical presentation and abnormal nerve conduction. 47 subjects with suspected CTS were enrolled. All patients were tested with nerve conduction studies and ULNT1. Considering results as positive in the presence of reproduction of symptoms on affected upper limb, or side-to-side differences in elbow extension, or symptoms modified by lateral neck side-bending, we estimated sensitivity as 91.67%, specificity as 15%, positive likelihood ratio as 1.0784, negative likelihood ratio as 0.5556, and post-test probability for negative test as 40%. Using a new criterion, i.e. the reproduction of symptoms only in the first three digits of the affected hand, we estimated sensitivity as 54.17%, specificity as 70%, positive and negative likelihood ratios as 1.8056 and 0.6548, respectively, and post-test probability for positive test as 68%. Our investigation suggests that the reproduction of the typical current CTS symptoms in the affected hand during ULNT1 testing, improves estimation of the probability of the presence of this condition, even if this test alone cannot be used to diagnose CTS. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Bonfiglioli, Roberta; Calabrese, Monica; Marinelli, Francesco; Violante, Francesco Saverio; Pillastrini, Paolo] Alma Mater Studiorum Univ Bologna, Dept Internal Med Geriatr & Nephrol, Sect Occupat Med, I-40138 Bologna, Italy. [Vanti, Carla] Univ Bologna, Sch Physiotherapy, I-40055 Bologna, Italy. [Guccione, Andrew] US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Off Res & Dev, Washington, DC 20420 USA. RP Pillastrini, P (reprint author), Alma Mater Studiorum Univ Bologna, Dept Internal Med Geriatr & Nephrol, Sect Occupat Med, Via P Palagi 9, I-40138 Bologna, Italy. EM cavanti@tin.it; roberta.bonfiglioli@unibo.it; monica.calabrese5@unibo.it; francesco.marinelli5@unibo.it; andrewguccione@cox.net; francesco.violante@unibo.it; paolo.pillastrini@unibo.it RI Pillastrini, Paolo/R-4901-2016; OI VANTI, CARLA/0000-0002-7741-9200 NR 55 TC 9 Z9 9 U1 1 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1356-689X J9 MANUAL THER JI Man. Ther. PD JUN PY 2011 VL 16 IS 3 BP 258 EP 263 DI 10.1016/j.math.2010.11.003 PG 6 WC Rehabilitation SC Rehabilitation GA 772AH UT WOS:000291201300008 PM 21185222 ER PT J AU Subramanian, S Shahaf, G Ozeri, E Miller, LM Vandenbark, AA Lewis, EC Offner, H AF Subramanian, Sandhya Shahaf, Galit Ozeri, Eyal Miller, Lisa M. Vandenbark, Arthur A. Lewis, Eli C. Offner, Halina TI Sustained expression of circulating human alpha-1 antitrypsin reduces inflammation, increases CD4+FoxP3+Treg cell population and prevents signs of experimental autoimmune encephalomyelitis in mice SO METABOLIC BRAIN DISEASE LA English DT Article DE hAAT; EAE; Tregs; Pro-inflammatory cytokines; CCR6 ID REGULATORY T-CELLS; OBSTRUCTIVE PULMONARY-DISEASE; ALPHA(1)-ANTITRYPSIN DEFICIENCY; RHEUMATOID-ARTHRITIS; AUGMENTATION THERAPY; MULTIPLE-SCLEROSIS; ULCERATIVE-COLITIS; DIABETES-MELLITUS; IMPAIRED ACTIVITY; TH17 RESPONSES AB Alpha-1-antitrypsin (AAT) is the primary circulating serine protease inhibitor, and is known to exert potent anti-inflammatory effects and to inhibit the progression of several autoimmune diseases. In this study, transgenic mice that over-express surfactant-driven human (h)AAT on the C57BL/6 background were evaluated for resistance to MOG-35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE), compared to WT C57BL/6 control mice. According to the results, sustained levels of circulating hAAT profoundly inhibited induction of clinical signs, inflammatory lesions and demyelination observed in WT mice with EAE, concomitant with enhanced levels of CD4+FoxP3+ Treg cells, reduced secretion of MOG peptide-induced pro-inflammatory cytokines, IL-17, IL-1 beta & IL-6, diminished expression of caspase-1 and enhanced expression of CCR6. These results implicate hAAT as a potent immunoregulatory agent worthy of further investigation as a potential therapy in human autoimmune diseases including multiple sclerosis. C1 [Subramanian, Sandhya; Miller, Lisa M.; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Neuroimmunol Res RD 31, Portland, OR 97239 USA. [Shahaf, Galit; Ozeri, Eyal; Lewis, Eli C.] Ben Gurion Univ Negev, Fac Hlth Sci, Beer Sheva, Israel. [Miller, Lisa M.; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland VA Med Ctr, Neuroimmunol Res RD 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu RI LEWIS, ELI/F-1552-2012 FU Biomedical Laboratory R&D Service, Department of Veterans' Affairs; Israel Science Foundation [1027/07] FX This work was supported by the Biomedical Laboratory R&D Service, Department of Veterans' Affairs and the Israel Science Foundation 1027/07. NR 52 TC 22 Z9 25 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD JUN PY 2011 VL 26 IS 2 BP 107 EP 113 DI 10.1007/s11011-011-9239-9 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 774OT UT WOS:000291396700002 PM 21437674 ER PT J AU Dziennis, S Mader, S Akiyoshi, K Ren, XF Ayala, P Burrows, GG Vandenbark, AA Herson, PS Hurn, PD Offner, HA AF Dziennis, Suzan Mader, Sarah Akiyoshi, Kozaburo Ren, Xuefang Ayala, Patricia Burrows, Gregory G. Vandenbark, Arthur A. Herson, Paco S. Hurn, Patricia D. Offner, Halina A. TI Therapy with recombinant T-cell receptor ligand reduces infarct size and infiltrating inflammatory cells in brain after middle cerebral artery occlusion in mice SO METABOLIC BRAIN DISEASE LA English DT Article DE Cerebral ischemia; T-cells; Inflammation; Neuroprotection; Therapeutic ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ISCHEMIC-STROKE; RAT-BRAIN; MULTIPLE-SCLEROSIS; MESSENGER-RNA; ACTIVATION; CD44; LYMPHOCYTES; MECHANISMS; EXPRESSION AB Stroke induces a biphasic effect on the peripheral immune response that involves early activation of peripheral leukocytes followed by severe immunosuppression and atrophy of the spleen. Peripheral immune cells, including T lymphocytes, migrate to the brain and exacerbate the developing infarct. Recombinant T-cell receptor (TCR) Ligand (RTL)551 is designed as a partial TCR agonist for myelin oligodendrocyte glycoprotein (MOG)-reactive T cells and has demonstrated the capacity to limit infarct volume and inflammation in brain when administered to mice undergoing middle cerebral artery occlusion (MCAO). The goal of this study was to determine if RTL551 could retain protection when given within the therapeutically relevant 4 h time window currently in clinical practice for stroke patients. RTL551 was administered subcutaneously 4 h after MCAO, with repeated doses every 24 h until the time of euthanasia. Cell numbers were assessed in the brain, blood, spleen and lymph nodes and infarct size was measured after 24 and 96 h reperfusion. RTL551 reduced infarct size in both cortex and striatum at 24 h and in cortex at 96 h after MCAO and inhibited the accumulation of inflammatory cells in brain at both time points. At 24 h post-MCAO, RTL551 reduced the frequency of the activation marker, CD44, on T-cells in blood and in the ischemic hemisphere. Moreover, RTL551 reduced expression of the chemokine receptors, CCR5 in lymph nodes and spleen, and CCR7 in the blood and lymph nodes. These data demonstrate effective treatment of experimental stroke with RTL551 within a therapeutically relevant 4 h time window through immune regulation of myelin-reactive inflammatory T-cells. C1 [Offner, Halina A.] Portland VA Med Ctr, Neuroimmunol Res R&D 31, Portland, OR 97239 USA. [Vandenbark, Arthur A.; Offner, Halina A.] Vet Affairs Med Ctr, Portland, OR 97239 USA. [Dziennis, Suzan; Mader, Sarah; Akiyoshi, Kozaburo; Ren, Xuefang; Ayala, Patricia; Herson, Paco S.; Hurn, Patricia D.; Offner, Halina A.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Burrows, Gregory G.; Vandenbark, Arthur A.; Offner, Halina A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Burrows, Gregory G.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. RP Offner, HA (reprint author), Portland VA Med Ctr, Neuroimmunol Res R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIH [NR003521, NS047661]; Collins Medical Trust; AHA [09POST2190040]; Biomedical Laboratory R&D Service, Department of Veterans' Affairs FX The authors wish to thank Dr. Sushmita Sinha and Ms. Sandhya Subramanian for helpful discussions and Ms. Eva Niehaus for assistance in preparing the manuscript. This work was supported by NIH Grant NR003521 (PDH), NIH Grant NS047661 (AAV), the Collins Medical Trust (SD), AHA grant 09POST2190040 (SD), and the Biomedical Laboratory R&D Service, Department of Veterans' Affairs. NR 40 TC 19 Z9 19 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD JUN PY 2011 VL 26 IS 2 BP 123 EP 133 DI 10.1007/s11011-011-9241-2 PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 774OT UT WOS:000291396700004 PM 21472429 ER PT J AU Niers, JM Kerami, M Pike, L Lewandrowski, G Tannous, BA AF Niers, Johanna M. Kerami, Mariam Pike, Lisa Lewandrowski, Grant Tannous, Bakhos A. TI Multimodal In Vivo Imaging and Blood Monitoring of Intrinsic and Extrinsic Apoptosis SO MOLECULAR THERAPY LA English DT Article ID GAUSSIA LUCIFERASE; CASPASE-3 ACTIVATION; CANCER-THERAPY; PROTEASES; NECROSIS; CULTURE; STRESS; CELLS; ASSAY AB Noninvasive detection and in vivo imaging of apoptosis plays a critical role in the development of therapeutics in many different fields including cancer. We have developed an apoptosis biosensor by fusing green fluorescent protein (GFP) to the N-terminus of the naturally secreted Gaussia luciferase separated by a caspase-3 cleavage peptide consisting of aspartic acid (D), glutamic acid (E), valine (V), and aspartic acid (D) or DEVD. We showed that this fusion is retained in the cytoplasm of cells in an inactive form. Upon apoptosis, the DEVD peptide is cleaved in response to caspase-3 activation, freeing ssGluc, which can now enter the secretory pathway where it is folded properly and is released from the cells and can be detected in the conditioned medium in culture or in blood of live animals ex vivo over time. Because Gluc is secreted from cells via conventional pathway through the endoplasmic reticulum (ER), Golgi and vesicles, we showed that the presence of Gluc in these compartments in response to apoptosis can be visualized in vivo using bioluminescence imaging. This reporter provides a valuable tool for imaging and real-time monitoring of apoptosis and is compatible with high-throughput functional screening application in cultured cells and animal models. C1 [Niers, Johanna M.; Kerami, Mariam; Pike, Lisa; Lewandrowski, Grant; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Charlestown, MA 02129 USA. [Niers, Johanna M.; Kerami, Mariam] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA 02129 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU NIH/NCI [P50CA86355]; NIH/NINDS [1R21NS061051, 1R01NS064983, P30NS045776] FX This work was supported partly by grants from NIH/NCI P50CA86355, NIH/NINDS 1R21NS061051, 1R01NS064983 and P30NS045776. We thank Dr Ralph Weissleder, Director of the Center for Molecular Imaging Research-MGH for the use of the CCD cameral; Dr Rampyari Walia (Targeting Systems) for cloning the GFP-DEVD-Gluc fusion in pCMV plasmid; Dr Xandra Breakefield for scientific discussions; Ms Lee-Ann Tjon-Kon-Fat for technical assistance; and Dr Euiheon Chung for assistance with the breast cancer metastasis model. NR 24 TC 23 Z9 23 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2011 VL 19 IS 6 BP 1090 EP 1096 DI 10.1038/mt.2011.17 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 772PA UT WOS:000291244900012 PM 21343914 ER PT J AU Pinto, D Darvishi, K Shi, XH Rajan, D Rigler, D Fitzgerald, T Lionel, AC Thiruvahindrapuram, B MacDonald, JR Mills, R Prasad, A Noonan, K Gribble, S Prigmore, E Donahoe, PK Smith, RS Park, JH Hurles, ME Carter, NP Lee, C Scherer, SW Feuk, L AF Pinto, Dalila Darvishi, Katayoon Shi, Xinghua Rajan, Diana Rigler, Diane Fitzgerald, Tom Lionel, Anath C. Thiruvahindrapuram, Bhooma MacDonald, Jeffrey R. Mills, Ryan Prasad, Aparna Noonan, Kristin Gribble, Susan Prigmore, Elena Donahoe, Patricia K. Smith, Richard S. Park, Ji Hyeon Hurles, Matthew E. Carter, Nigel P. Lee, Charles Scherer, Stephen W. Feuk, Lars TI Comprehensive assessment of array-based platforms and calling algorithms for detection of copy number variants SO NATURE BIOTECHNOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; STRUCTURAL VARIATION; MICROARRAY PLATFORMS; RESOLUTION ANALYSIS; SPECTRUM; CGH; POLYMORPHISMS; CHROMOSOMES; ASSOCIATION; DIAGNOSTICS AB We have systematically compared copy number variant (CNV) detection on eleven microarrays to evaluate data quality and CNV calling, reproducibility, concordance across array platforms and laboratory sites, breakpoint accuracy and analysis tool variability. Different analytic tools applied to the same raw data typically yield CNV calls with <50% concordance. Moreover, reproducibility in replicate experiments is <70% for most platforms. Nevertheless, these findings should not preclude detection of large CNVs for clinical diagnostic purposes because large CNVs with poor reproducibility are found primarily in complex genomic regions and would typically be removed by standard clinical data curation. The striking differences between CNV calls from different platforms and analytic tools highlight the importance of careful assessment of experimental design in discovery and association studies and of strict data curation and filtering in diagnostics. The CNV resource presented here allows independent data evaluation and provides a means to benchmark new algorithms. C1 [Feuk, Lars] Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, SciLifeLab Uppsala, Uppsala, Sweden. [Pinto, Dalila; Lionel, Anath C.; Thiruvahindrapuram, Bhooma; MacDonald, Jeffrey R.; Prasad, Aparna; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. [Darvishi, Katayoon; Shi, Xinghua; Mills, Ryan; Noonan, Kristin; Smith, Richard S.; Park, Ji Hyeon; Lee, Charles] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Rajan, Diana; Rigler, Diane; Fitzgerald, Tom; Gribble, Susan; Prigmore, Elena; Hurles, Matthew E.; Carter, Nigel P.] Sanger Inst, Cambridge, England. [Noonan, Kristin; Donahoe, Patricia K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. RP Feuk, L (reprint author), Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, SciLifeLab Uppsala, Uppsala, Sweden. EM lars.feuk@igp.uu.se RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013; Prasad, Aparna/N-4253-2015; Mills, Ryan/A-1979-2011; OI Scherer, Stephen /0000-0002-8326-1999; Prasad, Aparna/0000-0002-6786-2313; Mills, Ryan/0000-0003-3425-6998; Fitzgerald, Tomas/0000-0002-2370-8496 FU Genome Canada/Ontario Genomics Institute; Canadian Institutes of Health Research (CIHR) [213997]; McLaughlin Centre; Canadian Institute of Advanced Research; Hospital for Sick Children (SickKids) Foundation; US National Institutes of Health (NIH) [HD055150]; Department of Pathology at Brigham and Women's Hospital in Boston and NIH [HG005209, HG004221, CA111560]; Wellcome Trust [WT077008]; Netherlands Organization for Scientific Research [Rubicon 825.06.031]; Harvard Medical School; Goran Gustafsson Foundation; Swedish Foundation for Strategic Research; [HD007396] FX We thank J. Rickaby and M. Lee for excellent technical assistance. We thank colleagues at Affymetrix, Agilent, Illumina and NimbleGen, and Biodiscovery for sharing data, sharing software and technical assistance. The Toronto Centre for Applied Genomics at the Hospital for Sick Children is acknowledged for database, technical assistance and bioinformatics support. This work was supported by funding from the Genome Canada/Ontario Genomics Institute, the Canadian Institutes of Health Research (CIHR), the McLaughlin Centre, the Canadian Institute of Advanced Research, the Hospital for Sick Children (SickKids) Foundation, a Broad SPARC Project award to P.K.D. and C.L., US National Institutes of Health (NIH) grant HD055150 to P.K.D., and the Department of Pathology at Brigham and Women's Hospital in Boston and NIH grants HG005209, HG004221 and CA111560 to C.L. N.P.C., D. Rajan, D. Rigler, T.F., S.G. and E.P. are supported by the Wellcome Trust (grant no. WT077008). D.P. is supported by fellowships from the Canadian Institutes of Health Research (no. 213997) and the Netherlands Organization for Scientific Research (Rubicon 825.06.031). X.S. is supported by a T32 Harvard Medical School training grant, and K.N. is supported by a T32 institutional training grant (HD007396). S.W.S. holds the GlaxoSmithKline-CIHR Pathfinder Chair in Genetics and Genomics at the University of Toronto and the Hospital for Sick Children (Canada). L.F. is supported by the Goran Gustafsson Foundation and the Swedish Foundation for Strategic Research. NR 49 TC 186 Z9 193 U1 2 U2 27 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 JUN PY 2011 VL 29 IS 6 BP 512 EP U76 DI 10.1038/nbt.1852 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 773WL UT WOS:000291342100017 PM 21552272 ER PT J AU Baba, A Ohtake, F Okuno, Y Yokota, K Okada, M Imai, Y Ni, M Meyer, CA Igarashi, K Kanno, J Brown, M Kato, S AF Baba, Atsushi Ohtake, Fumiaki Okuno, Yosuke Yokota, Kenichi Okada, Maiko Imai, Yuuki Ni, Min Meyer, Clifford A. Igarashi, Katsuhide Kanno, Jun Brown, Myles Kato, Shigeaki TI PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B SO NATURE CELL BIOLOGY LA English DT Article ID DOMAIN-CONTAINING PROTEINS; HEPATIC GLUCONEOGENESIS; CHROMATIN MODIFICATIONS; GLUCOSE-METABOLISM; NUCLEAR RECEPTORS; DIOXIN RECEPTOR; TRANSCRIPTION; COACTIVATOR; FAMILY; PGC-1 AB Reversible histone methylation and demethylation are highly regulated processes that are crucial for chromatin reorganization and regulation of gene transcription in response to extracellular conditions. However, the mechanisms that regulate histone-modifying enzymes are largely unknown. Here, we characterized a protein kinase A (PKA)-dependent histone lysine demethylase complex, PHF2-ARID5B. PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. We found that phosphorylated PHF2 then associates with ARID5B, a DNA-binding protein, and induce demethylation of methylated ARID5B. This modification leads to targeting of the PHF2 ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark. These findings suggest that the PHF2 ARID5B complex is a signal-sensing modulator of histone methylation and gene transcription, in which phosphorylation of PHF2 enables subsequent formation of a competent and specific histone demethylase complex. C1 [Baba, Atsushi; Ohtake, Fumiaki; Okuno, Yosuke; Yokota, Kenichi; Okada, Maiko; Imai, Yuuki; Kato, Shigeaki] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan. [Ohtake, Fumiaki; Okuno, Yosuke; Okada, Maiko; Kato, Shigeaki] Japan Sci & Technol Agcy, ERATO, Kawaguchishi, Saitama 3320012, Japan. [Imai, Yuuki; Ni, Min; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Imai, Yuuki; Ni, Min; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Meyer, Clifford A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Meyer, Clifford A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Igarashi, Katsuhide; Kanno, Jun] Natl Inst Hlth Sci, Div Cellular & Mol Toxicol, Setagaya Ku, Tokyo 1588501, Japan. RP Kato, S (reprint author), Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1130032, Japan. EM uskato@mail.ecc.u-tokyo.ac.jp OI Brown, Myles/0000-0002-8213-1658 FU Ministry of Education, Culture, Sports, Science and Technology, MEXT, Japan; JSPS; Naito Foundation FX We thank D. D. Moore for critical discussion, R. Sato and J. Inoue for providing materials, N. Moriyama and S. Fujiyama for technical assistance and M. Yamaki for manuscript preparation. This work was supported in part by Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology, MEXT, Japan, JSPS, and The Naito Foundation (to F.O. and S.K.). NR 37 TC 61 Z9 66 U1 6 U2 17 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 JUN PY 2011 VL 13 IS 6 BP 668 EP U101 DI 10.1038/ncb2228 PG 23 WC Cell Biology SC Cell Biology GA 771HI UT WOS:000291147400007 PM 21532585 ER PT J AU Saylor, PJ AF Saylor, Philip J. TI Denosumab-a new option for solid tumors metastatic to bone SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID MULTIPLE-MYELOMA; ZOLEDRONIC ACID; BREAST-CANCER; LIGAND AB Zoledronic acid is a potent bisphosphonate used as the standard therapy for the prevention of skeletal-related events in patients with solid tumors metastatic to bone. Three phase III studies have reported head-to-head comparisons of zoledronic acid with denosumab, an inhibitor of the RANK signaling pathway. C1 Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, 55 Fruit St,Yawkey 7E Boston, Boston, MA 02114 USA. EM psaylor@partners.org NR 10 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 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD JUN PY 2011 VL 8 IS 6 BP 322 EP 324 DI 10.1038/nrclinonc.2011.70 PG 4 WC Oncology SC Oncology GA 771ZM UT WOS:000291199200004 PM 21556026 ER PT J AU Eichler, AF Chung, E Kodack, DP Loeffler, JS Fukumura, D Jain, RK AF Eichler, April F. Chung, Euiheon Kodack, David P. Loeffler, Jay S. Fukumura, Dai Jain, Rakesh K. TI The biology of brain metastases-translation to new therapies SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; HUMAN BREAST-CANCER; ENDOTHELIAL GROWTH-FACTOR; P-GLYCOPROTEIN INHIBITOR; II RANDOMIZED-TRIAL; ATHYMIC NUDE-MICE; STEM-LIKE CELLS; RADIATION-THERAPY; PHASE-III; IN-VIVO AB Brain metastases are a serious obstacle in the treatment of patients with solid tumors and contribute to the morbidity and mortality of these cancers. It is speculated that the frequency of brain metastasis is increasing for several reasons, including improved systemic therapy and survival, and detection of metastases in asymptomatic patients. The lack of preclinical models that recapitulate the clinical setting and the exclusion of patients with brain metastases from most clinical trials have slowed progress. Molecular factors contributing to brain metastases are being elucidated, such as genes involved in cell adhesion, extravasation, metabolism, and cellular signaling. Furthermore, the role of the unique brain microenvironment is beginning to be explored. Although the presence and function of the blood-brain barrier in metastatic tumors is still poorly understood, it is likely that some tumor cells are protected from therapeutics by the blood-tumor barrier, creating a sanctuary site. This Review discusses what is known about the biology of brain metastases, what preclinical models are available to study the disease, and which novel therapeutic strategies are being studied in patients. C1 [Eichler, April F.; Jain, Rakesh K.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI Chung, Euiheon/0000-0002-3326-6927 FU National Institutes of Health [P01-CA080124, R01-CA085140, R01-CA115767, R01-CA126642, R01-CA096915, R21-CA135605, U01-CA062490]; Federal Share Income Grant [T32-CA073479]; Department of Defense Breast Cancer Research [W81XWH-10-1-0016]; Massachusetts Biomedical Research Corporation; Gwangju Institute of Science and Technology, Gwangju, Republic of Korea FX We thank J. Engelman, S. Goel, L. Xu, I. J. Fidler, R. S. Kerbel, W. Cruz-Munoz and S. Mohla for their helpful comments on the manuscript. This work was supported by the National Institutes of Health grants P01-CA080124 (R. K. Jain and D. Fukumura), R01-CA085140, R01-CA115767 and R01-CA126642 (R. K. Jain), R01-CA096915 (D. Fukumura), R21-CA135605 and U01-CA062490 (A. F. Eichler), a Federal Share Income Grant (R. K. Jain and D. Fukumura), T32-CA073479 (D. P. Kodak) and Department of Defense Breast Cancer Research Innovator Award W81XWH-10-1-0016 (R. K. Jain). E. Chung was supported by a Tosteson postdoctoral fellowship award from the Massachusetts Biomedical Research Corporation. E. Chung also acknowledges support from his current institute: Gwangju Institute of Science and Technology, Gwangju, Republic of Korea. NR 156 TC 139 Z9 141 U1 4 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD JUN PY 2011 VL 8 IS 6 BP 344 EP 356 DI 10.1038/nrclinonc.2011.58 PG 13 WC Oncology SC Oncology GA 771ZM UT WOS:000291199200007 PM 21487419 ER PT J AU Carmeliet, P Jain, RK AF Carmeliet, Peter Jain, Rakesh K. TI Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; TUMOR VASCULATURE; BLOOD-VESSELS; ANTIANGIOGENIC THERAPY; RECTAL-CANCER; SOLID TUMORS; SHORT-TERM; INTERSTITIAL HYPERTENSION; GLIOBLASTOMA PATIENTS; IONIZING-RADIATION C1 [Carmeliet, Peter] Katholieke Univ Leuven VIB, Vesalius Res Ctr, B-3000 Louvain, Belgium. [Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumour Biol,Dept Radiat Oncol, Boston, MA 02114 USA. RP Carmeliet, P (reprint author), Katholieke Univ Leuven VIB, Vesalius Res Ctr, Campus Gasthuisberg,Herestr 49, B-3000 Louvain, Belgium. EM peter.carmeliet@vib-kuleuven.be; jain@steele.mgh.harvard.edu FU NCI NIH HHS [R01-CA115767, P01-CA80124, R01-CA126642, R01-CA85140] NR 126 TC 473 Z9 483 U1 8 U2 103 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 JUN PY 2011 VL 10 IS 6 BP 417 EP 427 DI 10.1038/nrd3455 PG 11 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 771NE UT WOS:000291165000019 PM 21629292 ER PT J AU Byers, AL Yaffe, K AF Byers, Amy L. Yaffe, Kristine TI Depression and risk of developing dementia SO NATURE REVIEWS NEUROLOGY LA English DT Review ID MILD COGNITIVE IMPAIRMENT; LATE-LIFE DEPRESSION; WHITE-MATTER HYPERINTENSITIES; ALZHEIMERS-DISEASE; HIPPOCAMPAL VOLUME; MAJOR DEPRESSION; GERIATRIC DEPRESSION; NEUROTROPHIC FACTOR; CEREBROVASCULAR-DISEASE; VASCULAR DEPRESSION AB Depression is highly common throughout the life course and dementia is common in late life. Depression has been linked with dementia, and growing evidence implies that the timing of depression may be important in defining the nature of this association. In particular, earlier-life depression (or depressive symptoms) has consistently been associated with a more than twofold increase in dementia risk. By contrast, studies of late-life depression and dementia risk have been conflicting; most support an association, yet the nature of this association (for example, if depression is a prodrome or consequence of, or risk factor for dementia) remains unclear. The likely biological mechanisms linking depression to dementia include vascular disease, alterations in glucocorticoid steroid levels and hippocampal atrophy, increased deposition of amyloid-beta plaques, inflammatory changes, and deficits of nerve growth factors. Treatment strategies for depression could interfere with these pathways and alter the risk of dementia. Given the projected increase in dementia incidence in the coming decades, understanding whether treatment for depression alone, or combined with other regimens, improves cognition is of critical importance. In this Review, we summarize and analyze current evidence linking late-life and earlier-life depression and dementia, and discuss the primary underlying mechanisms and implications for treatment. C1 [Byers, Amy L.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Byers, Amy L.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Byers, AL (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,116H, San Francisco, CA 94121 USA. EM amy.byers@ucsf.edu FU National Institute of Mental Health [K01 MH079093, R01 MH086498]; National Institute on Aging [K24 AG031155] FX This work was supported by the National Institute of Mental Health (grant K01 MH079093 to A. L. Byers and R01 MH086498 to K. Yaffe) and the National Institute on Aging (grant K24 AG031155 to K. Yaffe). NR 128 TC 168 Z9 177 U1 5 U2 46 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD JUN PY 2011 VL 7 IS 6 BP 323 EP 331 DI 10.1038/nrneurol.2011.60 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 774LM UT WOS:000291387500008 PM 21537355 ER PT J AU Waubant, E Mowry, EM Krupp, L Chitnis, T Yeh, EA Kuntz, N Ness, J Chabas, D Strober, J McDonald, J Belman, A Milazzo, M Gorman, M Weinstock-Guttman, B Rodriguez, M Oksenberg, JR James, JA AF Waubant, E. Mowry, E. M. Krupp, L. Chitnis, T. Yeh, E. A. Kuntz, N. Ness, J. Chabas, D. Strober, J. McDonald, J. Belman, A. Milazzo, M. Gorman, M. Weinstock-Guttman, B. Rodriguez, M. Oksenberg, J. R. James, J. A. CA US Pediat MS Network TI Common viruses associated with lower pediatric multiple sclerosis risk SO NEUROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ENVIRONMENTAL SUN EXPOSURE; INFECTION; HLA-DRB1-ASTERISK-1501; ANTIBODIES; RECEPTOR; CHILDREN; LOCUS AB Background: Because common viruses are encountered during childhood, pediatric multiple sclerosis (MS) offers a unique opportunity to investigate the influence of these viruses on disease susceptibility and the interactions between seroprevalence and select HLA genotypes. We studied seroprevalence for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV) type 1 and HLA-DRB1*1501/1503 status as predictors of pediatric MS. Methods: This was a retrospective analysis of prospectively collected demographic, clinical, and biologic data in subjects up to 18 years of age with early MS, control subjects seen at the same regional referral pediatric MS clinics, and additional healthy pediatric control subjects. Results: Patients with early pediatric MS (n = 189) and pediatric control subjects (n = 66) were tested. Epstein-Barr nuclear antigen-1 seropositivity was associated with an increased odds of MS (odds ratio [OR] 3.78, 95% confidence interval [CI] 1.52-9.38, p = 0.004) in analyses adjusted for age, sex, race, ethnicity, and HLA-DRB1*1501/1503 status. In multivariate analyses including EBV status, a remote infection with CMV (OR 0.27,95% CI 0.11-0.67, p = 0.004) was associated with a lower risk of developing MS. Although a remote infection with HSV-1 was not associated with an increased odds of MS, a strong interaction was found between HSV-1 status and HLA-DRB1 in predicting MS (p < 0.001). HSV-1 was associated with an increased risk of MS in those without a DRB1*15 allele (OR 4.11, 95% CI 1.17-14.37, p = 0.03), whereas the effect was reversed in those who were DRB1*15-positive (OR 0.07, 95% CI 0.02-0.32, p = 0.001). Conclusions: These findings suggest that some infections with common viruses may in fact lower MS susceptibility. If this is confirmed, the pathways for risk modification remain to be elucidated. Neurology (R) 2011;76:1989-1995 C1 [Waubant, E.; Chabas, D.; Strober, J.; McDonald, J.] Univ Calif San Francisco, UCSF Reg Pediat MS Ctr, San Francisco, CA 94143 USA. [Waubant, E.; Mowry, E. M.; Oksenberg, J. R.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Krupp, L.; Belman, A.; Milazzo, M.] Natl Pediat MS Ctr, Stony Brook, NY USA. [Chitnis, T.; Gorman, M.] Massachusetts Gen Hosp, Partners Pediat MS Ctr, Boston, MA 02114 USA. [Yeh, E. A.; Weinstock-Guttman, B.] Buffalo Pediat MS Ctr, Buffalo, NY USA. [Kuntz, N.; Rodriguez, M.] Mayo Clin, Pediat MS Ctr, Rochester, MN USA. [Ness, J.] Alabama Pediat MS Ctr, Birmingham, AL USA. [James, J. A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [James, J. A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. RP Waubant, E (reprint author), UCSF Reg Pediat Multiple Sclerosis Ctr, 350 Parnassus Ave,Suite 908, San Francisco, CA 94117 USA. EM emmanuelle.waubant@ucsf.edu OI Rodriguez, Moses/0000-0001-6328-6497 FU National Multiple Sclerosis Society; University of California; San Francisco; Stony Brook; Buffalo; University of Alabama Birmingham; Harvard University; Mayo Clinic; NIH [K23NS067055, RR015577, AI082714, U19AI082714, AR053483]; Nancy Davis Foundation; NMSS [RG2901D9/1]; National MS Society; National NS Society; Partners MS Center; Acorda Therapeutics Inc.; Bayer Schering Pharma; Biogen Idec; EMD Serono, Inc.; Genentech, Inc.; Teva Pharmaceutical Industries Ltd.; Novartis; sanofi-aventis; GlaxoSmithKline; MS Association of America; France Foundation; Eli Lilly and Company; MedImmune; Vertex Pharmaceuticals; Wyeth; ZymoGenetics; EPI-Q; Genzyme Corporation; Tibotec Therapeutics; Roche; Johnson Johnson; Janssen; ER Squibb Sons; NIH/NINDS; NIH; Jake Foundation; Children's Guild Foundation; Spinal Muscular Atrophy Foundation; Cooperative International Neuromuscular Research Group/U. S. Department of Education; Pfizer Inc; Mayo Rehabilitation Research Training Center; Conrad Hilton Foundation; Donald and Frances Herdrich Foundation; Canadian MS Society; Morphotek FX The Pediatric MS Network, initiated and sponsored by the National Multiple Sclerosis Society, includes the following centers: University of California, San Francisco, Stony Brook, Buffalo, University of Alabama Birmingham, Harvard University, and the Mayo Clinic. Dr. Mowry has a National MS Society Sylvia Lawry Fellowship Award and an NIH K23NS067055. Dr. Waubant is also supported by the Nancy Davis Foundation. Dr. James is supported by NIH RR015577, AI082714, U19AI082714, and AR053483. Dr. Oksenberg is supported by NMSS RG2901D9/1.; Dr. Waubant serves on scientific advisory boards for the NIH and Actelion Pharmaceuticals Ltd; has received speaker honoraria from Teva Pharmaceutical Industries Ltd.; has served as a consultant for Actelion Pharmaceuticals Ltd., Roche, and sanofi-aventis; has received free drugs for ongoing trials from sanofi-aventis and Biogen Idec; and receives research support from the NIH, the National MS Society, and the Nancy Davis Foundation. Dr. Mowry receives research support from the NIH, the National NS Society, and Partners MS Center. Dr. Krupp has served on scientific advisory boards for Acorda Therapeutics Inc., Genentech, Inc., Pfizer Inc, Novartis, and sanofi-aventis; has received funding for travel from Acorda Therapeutics Inc., Bayer Schering Pharma, Biogen Idec, EMD Serono, Inc., Genentech, Inc., Teva Pharmaceutical Industries Ltd., Novartis, and sanofi-aventis; has received honoraria from Acorda Therapeutics Inc., Bayer Schering Pharma, EMD Serono, Inc., Biogen Idec, Teva Pharmaceutical Industries Ltd., GlaxoSmithKline, the MS Association of America, and the France Foundation; has received royalties for publication of Fatigue in Multiple Sclerosis (Demos, 2005); serves as consultant for Leerink Swan, Gerson Lehrman Group, and Guidepoint Global; serves on speakers' bureaus for Bayer Schering Pharma, Biogen Idec, Teva Pharmaceutical Industries Ltd., and EMD Serono, Inc.; receives research support from Biogen Idec, EMD Serono, Inc., Teva Pharmaceutical Industries Ltd., Novartis, Genentech, Inc., Acorda Therapeutics Inc., BioMS Medical, the NIH (HD38107-02 [PI]), the National MS Society, the Lourie Foundation, and the Slomo and Cindy Silvian Foundation; has received license fee payments for a questionnaire she developed from the following companies: Eli Lilly and Company, MedImmune, Vertex Pharmaceuticals, Wyeth, ZymoGenetics, EPI-Q, Novartis, Genzyme Corporation, Tibotec Therapeutics, Genentech, Inc., Roche, sanofi-aventis, Johnson & Johnson, Janssen, and ER Squibb & Sons; and has served as an expert witness in medico-legal cases. Dr. Chitnis has served as a consultant for Biogen Idec, Teva Pharmaceutical Industries Ltd., and EMD Serono, Inc.; and receives research support from EMD Serono, Inc., the NIH/NINDS, and the National MS Society; and her spouse is employed by Novartis. Dr. Yeh has received research support from the NIH, the Jog for the Jake Foundation, the Children's Guild Foundation, and the National MS Society. Dr. Kuntz has received research support from the National MS Society, the Spinal Muscular Atrophy Foundation, Cooperative International Neuromuscular Research Group/U. S. Department of Education, and the NIH. Dr. Ness has served as a consultant for Merck Serono and receives research support from the NIH/NINDS, EMD Serono, Inc., and the National MS Society. Dr. Chabas has received honoraria from Teva Pharmaceutical Industries Ltd., EMD Serono, Inc., and Pfizer Inc; has received license fee payments and may accrue revenue on office of technology licensing Stanford Docket 501-085 (issued 5/6/2003): Osteopontin Related Compositions and Methods; and receives research support from the National MS Society and the Nancy Davis Foundation. Dr. Strober, J. McDonald, and Dr. Belman report no disclosures. M. Milazzo has received honoraria from Teva Pharmaceutical Industries Ltd. Dr. Gorman receives research support from the National MS Society. Dr.; Weinstock-Guttman serves on a medical advisory board for the National MS Society; has received funding for travel, serves on a speakers' bureau, and/or serves as a consultant to Bioge Idec, Teva Pharmaceutical Industries Ltd., EMD Serono, Inc., Pfizer Inc, Novartis, and Acorda Therapeutics Inc.; serves on the editorial boards of aan.com and Multiple Sclerosis International; and receives research support from Biogen Idec, EMD Serono, Inc., Teva Pharmaceutical Industries Ltd., Cyberonics, Inc., Novartis, Acorda Therapeutics Inc., the NIH, the National Science Foundation, the Jog for the Jake Foundation, and the National MS Society. Dr. Rodriguez serves on scientific advisory boards for the NIH/NINDS and Fast Forward LLC; serves on editorial advisory boards of the Annals of Neurology, Brain Pathology, the Journal of Neurovirology, and VerusMed; receives royalties from publication of Advances in Multiple Sclerosis (Current Topics in Microbiology and Immunology, vol. 318) (Springer-Verlag, 2008); may accrue revenue on patents re: Monoclonal Antibodies Which Promote Central Nervous System Remyelination and Method of Treating Autoimmune and/or Viral Induced Diseases That Are Mediated by CD8 Phenotype T Cells; and receives research support from Acorda Therapeutics, Inc., Mayo Rehabilitation Research Training Center, the NIH, the National MS Society, the Conrad Hilton Foundation, the Donald and Frances Herdrich Foundation, and the Canadian MS Society. Dr. Oksenberg serves as an Associate Editor for Annals of Neurology and receives research support from the NIH and the National MS Society. Dr. James serves on a scientific advisory board for InNexus Biotechnology, Inc.; serves as a consultant and on the speakers' bureaus for and has received speaker honoraria from Pfizer Inc and Novartis; and receives research support from Morphotek and the NIH. NR 28 TC 40 Z9 42 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2011 VL 76 IS 23 BP 1989 EP 1995 DI 10.1212/WNL.0b013e31821e552a PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 773WZ UT WOS:000291343500011 PM 21646624 ER PT J AU Walcott, BP Nahed, BV Kahle, KT Redjal, N Coumans, JV AF Walcott, Brian P. Nahed, Brian V. Kahle, Kristopher T. Redjal, Navid Coumans, Jean-Valery TI Determination of geographic variance in stroke prevalence using Internet search engine analytics SO NEUROSURGICAL FOCUS LA English DT Article DE search engine; stroke; epidemiology; prevalence; public health AB Object. Previous methods to determine stroke prevalence, such as nationwide surveys, are labor-intensive endeavors. Recent advances in search engine query analytics have led to a new metric for disease surveillance to evaluate symptomatic phenomenon, such as influenza. The authors hypothesized that the use of search engine query data can determine the prevalence of stroke. Methods. The Google Insights for Search database was accessed to analyze anonymized search engine query data. The authors' search strategy utilized common search queries used when attempting either to identify the signs and symptoms of a stroke or to perform stroke education. The search logic was as follows: (stroke signs + stroke symptoms + mini stroke - heat) from January 1, 2005, to December 31, 2010. The relative number of searches performed (the interest level) for this search logic was established for all 50 states and the District of Columbia. A Pearson product-moment correlation coefficient was calculated from the state-specific stroke prevalence data previously reported. Results. Web search engine interest level was available for all 50 states and the District of Columbia over the time period for January 1, 2005-December 31, 2010. The interest level was highest in Alabama and Tennessee (100 and 96, respectively) and lowest in California and Virginia (58 and 53, respectively). The Pearson correlation coefficient (r) was calculated to be 0.47 (p = 0.0005, 2-tailed). Conclusions. Search engine query data analysis allows for the determination of relative stroke prevalence. Further investigation will reveal the reliability of this metric to determine temporal pattern analysis and prevalence in this and other symptomatic diseases. (DOI: 10.3171/2011.2.FOCUS1124) C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 10 TC 6 Z9 6 U1 1 U2 6 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD JUN PY 2011 VL 30 IS 6 AR E19 DI 10.3171/2011.2.FOCUS1124 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 771NF UT WOS:000291165100020 PM 21631220 ER PT J AU Foster, MC Hwang, SJ Massaro, JM Hoffmann, U DeBoer, IH Robins, SJ Vasan, RS Fox, CS AF Foster, Meredith C. Hwang, Shih-Jen Massaro, Joseph M. Hoffmann, Udo DeBoer, Ian H. Robins, Sander J. Vasan, Ramachandran S. Fox, Caroline S. TI Association of Subcutaneous and Visceral Adiposity With Albuminuria: The Framingham Heart Study SO OBESITY LA English DT Article ID BODY-FAT DISTRIBUTION; CHRONIC KIDNEY-DISEASE; METABOLIC RISK-FACTORS; INSULIN SENSITIVITY; DIABETES-MELLITUS; CENTRAL OBESITY; SEX-DIFFERENCES; TISSUE VOLUMES; RENAL-DISEASE; ALL-CAUSE AB Microalbuminuria is a common condition associated with increased incidence of cardiovascular events and mortality. Abdominal obesity is associated with microalbuminuria, but studies linking visceral adipose tissue (VAT) and microalbuminuria are limited. Our objective was to determine the associations of albuminuria with VAT and subcutaneous adipose tissue (SAT). We performed a cross-sectional study in the Framingham Multi-Detector Computed Tomography (MDCT) cohort (n = 3,099, 48.2% women, mean age 53 years). VAT and SAT volumes were measured using computed tomography. Urinary albumin-to-creatinine ratio (UACR) was calculated from spot urine samples. Microalbuminuria was defined as a UACR >25 mg/g in women or >17 mg/g in men. Overall, 7.9% (n = 244) of the sample had microalbuminuria. Among men, VAT (odds ratio (OR) 1.48 per s.d., P < 0.0001) and SAT (OR 1.37 per s.d., P = 0.0002) were associated with microalbuminuria in minimally adjusted models, which remained significant after multivariable adjustment (VAT OR 1.34 per s.d., P = 0.001; SAT OR 1.28 per s.d., P = 0.005). Additionally, when considered jointly, VAT (P = 0.002) but not SAT (P = 0.2) was associated with microalbuminuria. In women, VAT was associated with microalbuminuria after minimal adjustment (OR 1.28, P = 0.01), but not after multivariable adjustment (OR 1.03, P = 0.8). In multivariable models in women, SAT was associated with a decreased odds of having microalbuminuria (OR 0.75 per s.d., P = 0.03). In conclusion, VAT is associated with microalbuminuria in men but not women. Albuminuria may be a manifestation of visceral adiposity. C1 [Foster, Meredith C.; Hwang, Shih-Jen; Robins, Sander J.; Vasan, Ramachandran S.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Foster, Meredith C.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [DeBoer, Ian H.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Robins, Sander J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. [Robins, Sander J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol & Metab, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [N01-HC-25195] FX The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). NR 40 TC 30 Z9 32 U1 1 U2 3 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 JUN PY 2011 VL 19 IS 6 BP 1284 EP 1289 DI 10.1038/oby.2010.308 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 769NG UT WOS:000291021600026 PM 21183930 ER PT J AU Santos, JLF Salemi, VMC Picard, MH Mady, C Coelho, OR AF Santos, Jose L. F. Salemi, Vera M. C. Picard, Michael H. Mady, Charles Coelho, Otavio R. TI Subclinical Regional Left Ventricular Dysfunction in Obese Patients With and Without Hypertension or Hypertrophy SO OBESITY LA English DT Article ID BODY-MASS INDEX; CONGESTIVE-HEART-FAILURE; WEIGHT-LOSS; STANDARDS COMMITTEE; OF-ECHOCARDIOGRAPHY; FOLLOW-UP; RECOMMENDATIONS; OVERWEIGHT; DISEASE; IMPACT AB We investigated the impact of obesity on the abnormalities of systolic and diastolic regional left ventricular (LV) function in patients with or without hypertension or hypertrophy, and without heart failure. We studied 120 individuals divided into 6 groups of 20 patients (42 +/- 6 years, 60 females) using standard and pulsed-wave tissue Doppler imaging (TDI) echocardiography, and heterogeneity index (HI): nonobese (I: no hypertension, no hypertrophy, control group; II: hypertension, no hypertrophy; III: hypertension and hypertrophy) and obese (IV: no hypertension, no hypertrophy; V: hypertension, no hypertrophy; VI: hypertension and hypertrophy). The criterion for obesity was BMI >= 30 kg/m(2), for hypertension was blood pressure >= 140/90 mm Hg, for hypertrophy in nonobese was LV mass/body surface area (BSA) >134 g/m(2) (men) and >110 mg/m(2) (women), and in obese was LV mass/height((2.7)) >50 (men) and >40 (women). Obese groups had normal LV ejection fraction compared with nonobese groups, but decreased longitudinal and radial systolic myocardial peak velocities (S'), and early diastolic myocardial peak velocity (E'). Also, a great variability of E' and late diastolic myocardial peak velocity (A') from the longitudinal basal region was observed in obese groups (E' basal nonobese: 11 +/- 7 vs. obese 19 +/- 11, P < 0.001, A' basal nonobese: 7 +/- 4 vs. obese 11 +/- 7, P < 0.001). Our findings were more evident when comparing groups IV with V and VI, with the latter having concentric hypertrophy and obvious segmental systolic and diastolic dysfunctions. Subclinical myocardial alterations and increased variability of the velocities were observed in obese groups, especially with hypertension and hypertrophy, reflecting impaired regional LV relaxation, segmental atrial, and systolic dysfunctions. C1 [Salemi, Vera M. C.; Mady, Charles] Univ Sao Paulo, Fac Med, Cardiomyopathy Unit, Heart Inst InCor,Hosp Clin, Sao Paulo, Brazil. [Santos, Jose L. F.; Coelho, Otavio R.] Univ Estadual Campinas, UNICAMP, Fac Ciencias Med, Sao Paulo, Brazil. [Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Picard, Michael H.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Picard, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. RP Salemi, VMC (reprint author), Univ Sao Paulo, Fac Med, Cardiomyopathy Unit, Heart Inst InCor,Hosp Clin, Sao Paulo, Brazil. EM verasalemi@uol.com.br RI Mady, Charles/C-8870-2012; Salemi, Vera/C-9104-2013; OI Mady, Charles/0000-0002-8838-199X; Salemi, Vera/0000-0002-7152-1810; Picard, Michael/0000-0002-9264-3243 NR 34 TC 6 Z9 6 U1 0 U2 1 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 JUN PY 2011 VL 19 IS 6 BP 1296 EP 1303 DI 10.1038/oby.2010.253 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 769NG UT WOS:000291021600028 PM 20966911 ER PT J AU Serra, V Scaltriti, M Prudkin, L Eichhorn, PJA Ibrahim, YH Chandarlapaty, S Markman, B Rodriguez, O Guzman, M Rodriguez, S Gili, M Russillo, M Parra, JL Singh, S Arribas, J Rosen, N Baselga, J AF Serra, V. Scaltriti, M. Prudkin, L. Eichhorn, P. J. A. Ibrahim, Y. H. Chandarlapaty, S. Markman, B. Rodriguez, O. Guzman, M. Rodriguez, S. Gili, M. Russillo, M. Parra, J. L. Singh, S. Arribas, J. Rosen, N. Baselga, J. TI PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer SO ONCOGENE LA English DT Article DE PI3K/mTOR; HER2; feedback; ERK; BEZ235 ID VIVO ANTITUMOR-ACTIVITY; PHASE-II; TRASTUZUMAB RESISTANCE; PATHWAY ACTIVATION; MEK INHIBITION; CELL-SURVIVAL; PTEN; MUTATIONS; RECEPTOR; PIK3CA AB There is a strong rationale to therapeutically target the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway in breast cancer since it is highly deregulated in this disease and it also mediates resistance to anti-HER2 therapies. However, initial studies with rapalogs, allosteric inhibitors of mTORC1, have resulted in limited clinical efficacy probably due to the release of a negative regulatory feedback loop that triggers AKT and ERK signaling. Since activation of AKT occurs via PI3K, we decided to explore whether PI3K inhibitors prevent the activation of these compensatory pathways. Using HER2-overexpressing breast cancer cells as a model, we observed that PI3K inhibitors abolished AKT activation. However, PI3K inhibition resulted in a compensatory activation of the ERK signaling pathway. This enhanced ERK signaling occurred as a result of activation of HER family receptors as evidenced by induction of HER receptors dimerization and phosphorylation, increased expression of HER3 and binding of adaptor molecules to HER2 and HER3. The activation of ERK was prevented with either MEK inhibitors or anti-HER2 monoclonal antibodies and tyrosine kinase inhibitors. Combined administration of PI3K inhibitors with either HER2 or MEK inhibitors resulted in decreased proliferation, enhanced cell death and superior anti-tumor activity compared with single agent PI3K inhibitors. Our findings indicate that PI3K inhibition in HER2-overexpressing breast cancer activates a new compensatory pathway that results in ERK dependency. Combined anti-MEK or anti-HER2 therapy with PI3K inhibitors may be required in order to achieve optimal efficacy in HER2-overexpressing breast cancer. This approach warrants clinical evaluation. Oncogene (2011) 30, 2547-2557; doi:10.1038/onc.2010.626; published online 31 January 2011 C1 [Baselga, J.] Vall Hebron Univ Hosp, VHIO, Expt Therapeut Program, E-08035 Barcelona, Spain. [Scaltriti, M.; Baselga, J.] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Boston, MA USA. [Prudkin, L.; Rodriguez, S.] Vall Hebron Inst Oncol, Mol Pathol Program, Barcelona, Spain. [Chandarlapaty, S.; Rosen, N.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Chandarlapaty, S.; Rosen, N.] Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Chem, New York, NY 10021 USA. [Markman, B.; Baselga, J.] Vall Hebron Univ Hosp, Dept Med Oncol, E-08035 Barcelona, Spain. [Parra, J. L.; Arribas, J.] Vall Hebron Inst Oncol, Growth Factors Lab, Barcelona, Spain. [Singh, S.] Prometheus Therapeut & Diagnost, San Diego, CA USA. [Arribas, J.; Baselga, J.] Univ Autonoma Barcelona, E-08193 Barcelona, Spain. [Arribas, J.] Inst Catalana Recerca & Estudis Acancats, Barcelona, Spain. [Baselga, J.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Baselga, J (reprint author), Vall Hebron Univ Hosp, VHIO, Expt Therapeut Program, Passeig Vall Hebron 119-129, E-08035 Barcelona, Spain. EM jbaselga@vhio.net RI Arribas, Joaquin/M-4482-2014 OI Arribas, Joaquin/0000-0002-0504-0664 FU Instituto de Salud Carlos III [PSO9/00623]; Breast Cancer Research Foundation; ERC [AdG09 250244] FX This research was supported by grants from the Instituto de Salud Carlos III (Intrasalud PSO9/00623), from the Breast Cancer Research Foundation and from the ERC (AdG09 250244). BEZ235 and NVP-AEW541 were kindly provided by C Garcia-Echeverria from Novartis, Basel, Switzerland. The AKT1/2/3 inhibitor was provided by Pradip Majumder at Merck Research Laboratories, Boston. Lapatinib was kindly provided by GlaxoSmithKline, Research Triangle Park, NJ. Torin1 was obtained from Whitehead/DFCI. Trastuzumab was kindly provided by F Hoffmann-La Roche, Basel, Switzerland. NR 54 TC 222 Z9 226 U1 4 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JUN PY 2011 VL 30 IS 22 BP 2547 EP 2557 DI 10.1038/onc.2010.626 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 771ZE UT WOS:000291198400006 PM 21278786 ER PT J AU Mohan, N Vakoc, B AF Mohan, Nishant Vakoc, Benjamin TI Principal-component-analysis-based estimation of blood flow velocities using optical coherence tomography intensity signals SO OPTICS LETTERS LA English DT Article ID ANGIOGRAPHY; MICROVASCULATURE AB The intensity signal in optical coherence tomography contains information about the translational velocity of scatterers, and can be used to quantify blood flow. We apply principal component analysis to efficiently extract this information. We also study use of nonuniform temporal sampling of the intensity signal to increase the range of quantifiable flow velocities. We demonstrate this technique in simulation, phantom and in vivo blood flow measurements, and highlight its potential to enable three-dimensional wide-field mapping of blood flow using OCT. (C) 2011 Optical Society of America C1 [Vakoc, Benjamin] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vakoc, B (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM bvakoc@partners.org FU NCI NIH HHS [K25 CA127465] NR 17 TC 8 Z9 9 U1 0 U2 1 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 JUN 1 PY 2011 VL 36 IS 11 BP 2068 EP 2070 PG 3 WC Optics SC Optics GA 771HZ UT WOS:000291149100040 PM 21633451 ER PT J AU Feudtner, C Kang, TI Hexem, KR Friedrichsdorf, SJ Osenga, K Siden, H Friebert, SE Hays, RM Dussel, V Wolfe, J AF Feudtner, Chris Kang, Tammy I. Hexem, Kari R. Friedrichsdorf, Stefan J. Osenga, Kaci Siden, Harold Friebert, Sarah E. Hays, Ross M. Dussel, Veronica Wolfe, Joanne TI Pediatric Palliative Care Patients: A Prospective Multicenter Cohort Study SO PEDIATRICS LA English DT Article DE pediatric care; palliative care; hospice care; chronic illness; technology dependence; polypharmacy ID SURVIVAL; TEAM AB OBJECTIVE: To describe demographic and clinical characteristics and outcomes of patients who received hospital-based pediatric palliative care (PPC) consultations. DESIGN, SETTING, AND PATIENTS: Prospective observational cohort study of all patients served by 6 hospital-based PPC teams in the United States and Canada from January to March 2008. RESULTS: There were 515 new (35.7%) or established (64.3%) patients who received care from the 6 programs during the 3-month enrollment interval. Of these, 54.0% were male, and 69.5% were identified as white and 8.1% as Hispanic. Patient age ranged from less than one month (4.7%) to 19 years or older (15.5%). Of the patients, 60.4% lived with both parents, and 72.6% had siblings. The predominant primary clinical conditions were genetic/congenital (40.8%), neuromuscular (39.2%), cancer (19.8%), respiratory (12.8%), and gastrointestinal (10.7%). Most patients had chronic use of some form of medical technology, with gastrostomy tubes (48.5%) being the most common. At the time of consultation, 47.2% of the patients had cognitive impairment; 30.9% of the cohort experienced pain. Patients were receiving many medications (mean: 9.1). During the 12-month follow-up, 30.3% of the cohort died; the median time from consult to death was 107 days. Patients who died within 30 days of cohort entry were more likely to be infants and have cancer or cardiovascular conditions. CONCLUSIONS: PPC teams currently serve a diverse cohort of children and young adults with life-threatening conditions.In contrast to the reported experience of adult-oriented palliative care teams, most PPC patients are alive for more than a year after initiating PPC. Pediatrics 2011;127:1094-1101 C1 [Feudtner, Chris; Kang, Tammy I.; Hexem, Kari R.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Friedrichsdorf, Stefan J.; Osenga, Kaci] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA. [Siden, Harold] Child & Family Res Inst, Vancouver, BC, Canada. [Friebert, Sarah E.] Akron Childrens Hosp, Akron, OH USA. [Hays, Ross M.] Seattle Childrens Hosp, Seattle, WA USA. [Dussel, Veronica; Wolfe, Joanne] Childrens Hosp Boston, Boston, MA USA. [Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Feudtner, C (reprint author), Childrens Hosp Philadelphia, 3535 Market St,Room 1523,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM feudtner@email.chop.edu FU Children's Hospital of Philadelphia FX Core funding for this project was provided by the Research Institute of The Children's Hospital of Philadelphia. NR 16 TC 91 Z9 95 U1 2 U2 10 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2011 VL 127 IS 6 BP 1094 EP 1101 DI 10.1542/peds.2010-3225 PG 8 WC Pediatrics SC Pediatrics GA 771GV UT WOS:000291146100051 PM 21555495 ER PT J AU Kleinman, RE Brown, RT Cutter, GR DuPaul, GJ Clydesdale, FM AF Kleinman, Ronald E. Brown, Ronald T. Cutter, Gary R. DuPaul, George J. Clydesdale, Fergus M. TI A Research Model for Investigating the Effects of Artificial Food Colorings on Children With ADHD SO PEDIATRICS LA English DT Article DE children; attention-deficit/hyperactivity disorder; artificial food colorings; elimination diet; food safety ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; GENETICALLY-MODIFIED FOODS; DOUBLE-BLIND CROSSOVER; FOLLOW-UP; FEINGOLD HYPOTHESIS; PRESCHOOL-CHILDREN; CLINICAL-TRIAL; DIET; BEHAVIOR AB The United Kingdom and European Union recently restricted the use of artificial food colorings (AFCs) to improve the health of children. These decisions provide an interesting case study of the role of scientific evidence in the assessment of food additives and risk to children's health and formulation of food policy. Although there continues to be uncertainty concerning the link between AFCs and attention-deficit/hyperactivity disorder (ADHD), policy decisions have been made that have far-reaching implications. In addition, publicity surrounding the policy changes may shape public perceptions concerning effective management of ADHD. We believe that the balance of existing evidence neither refutes nor supports the link between AFCs and ADHD, which highlights the need for carefully designed studies to further investigate the link between AFCs and ADHD. In this article we describe a model for such studies. In developing our model, we drew from current investigative standards in ADHD research, such as those used in the landmark Multimodal Treatment Study of Children With ADHD. These standards encompass methodologic considerations including sample selection, outcome assessment, and data analyses. It is our hope that this model research methodology may prove valuable in addressing design considerations in future studies of AFCs and ADHD with the goal of producing reliable data that will enable policy-makers to better formulate effective, evidence-based food-policy decisions. Pediatrics 2011; 127:e1575-e1584 C1 [Kleinman, Ronald E.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Kleinman, Ronald E.] Harvard Univ, Sch Med, Boston, MA USA. [Brown, Ronald T.] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. [Cutter, Gary R.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [DuPaul, George J.] Lehigh Univ, Dept Educ & Human Serv, Bethlehem, PA 18015 USA. [Clydesdale, Fergus M.] Univ Massachusetts, Dept Food Sci, Amherst, MA 01003 USA. RP Kleinman, RE (reprint author), Massachusetts Gen Hosp, Dept Pediat, CPZS 578,175 Cambridge St, Boston, MA 02114 USA. EM rkleinman@partners.org FU Cargill, Inc.; Coca-Cola Company; ConAgra Foods, Inc.; Kraft; Mars, Inc.; Nestle RD Center, Inc.; Pepsi Cola, Inc.; Tate and Lyle North America, Unilever NA; Massachusetts Department of Agricultural Resources; University of Massachusetts Amherst; Eli Lilly; Shire Pharmaceuticals; UMass Amherst Food Science Strategic Policy Alliance FX With reference to this article, only Dr Clydesdale has a working relationship with a company involved in the manufacture of food colorings. The UMass Amherst Food Science Strategic Policy Alliance receives funding from Cargill, Inc, Coca-Cola Company, ConAgra Foods, Inc, Kraft, Mars, Inc, Nestle R&D Center, Inc, Pepsi Cola, Inc, Tate and Lyle North America, Unilever NA, Massachusetts Department of Agricultural Resources (grant), and University of Massachusetts Amherst. Dr Kleinman has served on the scientific advisory boards of General Mills, Beechnut, Hero Foods, the Grain Foods Foundation, and Burger King and consulted for Elanco, Mead Johnson, and Cantox; Dr Brown has served on a scientific advisory board for Shire Pharmaceuticals and has received grant support from Eli Lilly; Dr Cutter has served on data and safety monitoring committees for AntiSense Pharmaceuticals, Sanofi-Aventis, Bayhill Pharmaceuticals Inc, Bayer Pharmaceuticals, BioMS Pharmaceuticals, Daichi-Sankyo Pharmaceuticals, Enzo Pharmaceuticals, Esai Pharmaceuticals, GlaxoSmithKline Pharmaceuticals, Genentech Pharmaceuticals, Genmab Biopharmaceuticals, Incyte Pharmaceuticals, Medivation Pharmaceuticals, Millennium Pharmaceuticals, Novartis Pharmaceuticals, Peptimmune Pharmaceuticals, PTC Therapeutics, Teva Pharmaceuticals, Vivus Pharmaceuticals, the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the [National Multiple Sclerosis Society] NMSS and has served as a consultant to Alexion Pharmaceuticals, Accentia Pharmaceuticals, Bayer Pharmaceuticals, Barofold Pharmaceuticals, Biogen Idec Pharmaceuticals, CibaVision, Millenium Pharmaceuticals, Consortium of MS Centers, an MS-CORE-and NMSS-funded research group, Novartis Pharmaceuticals, Klein-Buendel Incorporated, and Somnus Pharmaceuticals; Dr DuPaul receives research grant support from Shire Pharmaceuticals; and Dr Clydesdale has served on the scientific advisory boards of General Mills, Mars Snackfood US, McCain Foods, Tate and Lyle, ConAgra, Unilever, and the Coca-Cola Company, has consulted with Cantox, and serves on the board of directors of Sensient Technologies, Inc (a manufacturer of both artificial and natural food colorings).; This article was prepared at a meeting convened by the University of Massachusetts (UMass) Amherst Food Science Strategic Policy Alliance on April 1-3, 2009, to address the issue of the current state of research in food policy and ADHD and was supported by the UMass Amherst Food Science Strategic Policy Alliance and its members, including the Massachusetts Department of Agricultural Resources (grant) and UMass Amherst. The meeting gathered thought leaders in the areas of food science and policy and clinical psychology with emphasis on the design and conduct of clinical trials that assess the effects of pharmacotherapeutic and behavioral interventions for ADHD, pediatric nutrition with emphasis on assessing the bioavailability and metabolism of nutritional exposures, and biostatistics and the design and conduct of clinical trials and research projects. Participants were selected on the basis of large-scale screening and in-depth personal interviews. Moderators were selected to facilitate discussion, and a writer with expertise in medical publications was chosen to work with panel members to develop a consensus report based on expert panel recommendations. The UMass Amherst Food Science Strategic Policy Alliance is a policy program based at UMass Amherst with members from industry, government ( including the US Food and Drug Administration and US Department of Agriculture), and university faculty and students. The opinions and positions taken in this consensus report are scientifically based and not influenced by the UMass Amherst Food Science Strategic Policy Alliance or its members. Editorial assistance for this project was provided by BioScience Communications with financial support from the UMass Amherst Food Science Strategic Policy Alliance. NR 84 TC 2 Z9 2 U1 2 U2 38 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 JUN PY 2011 VL 127 IS 6 BP E1575 EP E1584 DI 10.1542/peds.2009-2206 PG 10 WC Pediatrics SC Pediatrics GA 771GV UT WOS:000291146100027 PM 21576306 ER PT J AU Kosten, TA AF Kosten, Therese A. TI Pharmacologically targeting the P2rx4 gene on maintenance and reinstatement of alcohol self-administration in rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Ivermectin; Purinergic system; P2X(4) receptors; Relapse; Operant conditioning ID P2X(4) RECEPTOR CHANNELS; ETHANOL-SEEKING BEHAVIOR; DRUG-ADDICTION; ION CHANNELS; IVERMECTIN; RELAPSE; NEURONS; NEUROBIOLOGY; POTENTIATION; CONSUMPTION AB Genetic studies indicate that alcohol consumption associates with expression of the P2rx4 gene, a gene that codes for the P2X(4) receptor. This receptor is a subtype in the purinergic system of ligand-gated ion channels that when activated exerts excitatory effects in CNS. P2X(4) function is inhibited by alcohol and P2X(4) receptors are modulated positively by the antiparasitic agent, ivermectin. Two experiments were performed to test the ability of ivermectin to alter the behavioral effects of alcohol in rats. After alcohol exposure was achieved via the "drinking in the dark" procedure, separate groups of Sprague-Dawley rats were trained to lever press for either alcohol (10% ethanol/2% sucrose) or sucrose (3%) solutions in operant chambers. Rats were tested for maintenance of operant self-administration under a progressive ratio condition (Experiment 1) and for reinstatement of extinguished responding induced by solution presentation (Experiment 2) after ivermectin (0; 1-10 mg/kg; IP) administration. Ivermectin decreased the amount of work that the animal performed to obtain reinforcers in the maintenance study, particularly in the group reinforced with alcohol, and tended to decrease reinstated lever press responding. Conditioned approach behavior (head entries) was significantly reduced by ivermectin in both experiments. Reduction in motor activity was seen during the longer maintenance sessions but not in the shorter reinstatement sessions. Results suggest some support for ivermectin-like drugs as potential treatment agents for alcohol dependence. Caution is warranted due to modest specificity on behavior reinforced by alcohol, some reduction in general activity levels, and the lack of dose-response effects. (C) 2011 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Dept Psychiat & Behav Sci, Michael E Debakey Vet Adm Med Ctr, Houston, TX 77030 USA. RP Kosten, TA (reprint author), Baylor Coll Med, Dept Psychiat & Behav Sci, Michael E Debakey Vet Adm Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tkosten@bcm.edu FU [U01-AA013476] FX This research was supported by grant U01-AA013476. We greatly acknowledge the technical assistance provided by A. Aruffo, W. Huang, M. Kosten, P. O'Malley, M. Rengasamy, J. Taylor, W. Webb, and X. Xiang. NR 51 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUN PY 2011 VL 98 IS 4 BP 533 EP 538 DI 10.1016/j.pbb.2011.02.026 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 773GP UT WOS:000291295300006 PM 21402096 ER PT J AU Chen, ACH Huang, YY Sharma, SK Hamblin, MR AF Chen, Aaron C. -H. Huang, Ying-Ying Sharma, Sulbha K. Hamblin, Michael R. TI Effects of 810-nm Laser on Murine Bone-Marrow-Derived Dendritic Cells SO PHOTOMEDICINE AND LASER SURGERY LA English DT Article ID NF-KAPPA-B; CYTOCHROME-C-OXIDASE; INFLAMMATORY CYTOKINES; IMMUNE-RESPONSE; NITRIC-OXIDE; LEVEL; THERAPY; IRRADIATION; ACTIVATION; LIGHT AB Objective: The purpose of this study was to Investigate the effect of 810-nm low level laser therapy (LLLT) on dendritic cells (DC) in vitro. Background data: LLLT can enhance wound healing and increase cell proliferation and survival, and is used to treat inflammatory conditions. However there are reports that LLLT can stimulate leukocytes and could therefore be pro-inflammatory. Recently, DC have been found to play an important role in inflammation and immune response. Methods: Murine bone-marrow-derived DC were isolated, stimulated with lipopolysaccharide (LPS) or CpG oligodeoxynucleotide and treated with 810-nm laser, using fluences of 0.3, 3, and 30 J/cm(2) delivered at irradiances of 1, 10, and 100mW/cm(2) respectively. Confocal microscopy, flow cytometry for DC markers, viability using propidium iodide, enzyme-linked immunosorbent assays (ELISA) for secreted interleukin-12 (IL-12), and bioluminescence measurements in cells transduced with a reporter for toll-like receptor (TLR)-9/nuclear factor kappa B (NF-kappa B) activation, were performed. Results: LLLT changed the morphology of LPS-stimulated DC, increased their viability, and altered the balance of DC activation markers (major histocompatibility complex [MHC] class 2 up and CD86 down). LLLT reduced IL-12 secretion from DC stimulated by either LPS or CpG. LLLT reduced NF-kappa B activation in reporter cells stimulated with CpG. There was no obvious light dose response observed. Conclusions: Taken together, these data suggest that 810-nm LLLT has an anti-inflammatory effect on activated DC, possibly mediated by cyclic adenosine monophosphate (cAMP) and reduced NF-kappa B signaling. C1 [Chen, Aaron C. -H.; Huang, Ying-Ying; Sharma, Sulbha K.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM Hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program in TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research [FA9950-04-1-0079] FX This work was supported by NIH grant R01AI050875, Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514), and Air Force Office of Scientific Research (FA9950-04-1-0079). NR 40 TC 16 Z9 17 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-5418 J9 PHOTOMED LASER SURG JI Photomed. Laser Surg. PD JUN PY 2011 VL 29 IS 6 BP 383 EP 389 DI 10.1089/pho.2010.2837 PG 7 WC Surgery SC Surgery GA 771ZT UT WOS:000291199900003 PM 21214383 ER PT J AU Curtin, SJ Zhang, F Sander, JD Haun, WJ Starker, C Baltes, NJ Reyon, D Dahlborg, EJ Goodwin, MJ Coffman, AP Dobbs, D Joung, JK Voytas, DF Stupar, RM AF Curtin, Shaun J. Zhang, Feng Sander, Jeffry D. Haun, William J. Starker, Colby Baltes, Nicholas J. Reyon, Deepak Dahlborg, Elizabeth J. Goodwin, Mathew J. Coffman, Andrew P. Dobbs, Drena Joung, J. Keith Voytas, Daniel F. Stupar, Robert M. TI Targeted Mutagenesis of Duplicated Genes in Soybean with Zinc-Finger Nucleases SO PLANT PHYSIOLOGY LA English DT Article ID PLANTS; RESISTANCE; EXPRESSION; PROTEINS; DATABASE; PATHWAY; ARRAYS; DOMAIN; SEED; TOOL AB We performed targeted mutagenesis of a transgene and nine endogenous soybean (Glycine max) genes using zinc-finger nucleases (ZFNs). A suite of ZFNs were engineered by the recently described context-dependent assembly platform-a rapid, open-source method for generating zinc-finger arrays. Specific ZFNs targeting DICER-LIKE (DCL) genes and other genes involved in RNA silencing were cloned into a vector under an estrogen-inducible promoter. A hairy-root transformation system was employed to investigate the efficiency of ZFN mutagenesis at each target locus. Transgenic roots exhibited somatic mutations localized at the ZFN target sites for seven out of nine targeted genes. We next introduced a ZFN into soybean via whole-plant transformation and generated independent mutations in the paralogous genes DCL4a and DCL4b. The dcl4b mutation showed efficient heritable transmission of the ZFN-induced mutation in the subsequent generation. These findings indicate that ZFN-based mutagenesis provides an efficient method for making mutations in duplicate genes that are otherwise difficult to study due to redundancy. We also developed a publicly accessible Web-based tool to identify sites suitable for engineering context-dependent assembly ZFNs in the soybean genome. C1 [Curtin, Shaun J.; Haun, William J.; Coffman, Andrew P.; Stupar, Robert M.] Univ Minnesota, Dept Agron & Plant Genet, St Paul, MN 55108 USA. [Zhang, Feng; Starker, Colby; Baltes, Nicholas J.; Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [Zhang, Feng; Starker, Colby; Baltes, Nicholas J.; Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA. [Sander, Jeffry D.; Dahlborg, Elizabeth J.; Goodwin, Mathew J.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Sander, Jeffry D.; Dahlborg, Elizabeth J.; Goodwin, Mathew J.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Sander, Jeffry D.; Dahlborg, Elizabeth J.; Goodwin, Mathew J.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Sander, Jeffry D.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA 02115 USA. [Reyon, Deepak; Dobbs, Drena] Iowa State Univ, Dept Genet Dev & Cell Biol, Bioinformat & Computat Biol Program, Ames, IA 50011 USA. RP Stupar, RM (reprint author), Univ Minnesota, Dept Agron & Plant Genet, St Paul, MN 55108 USA. EM rstupar@umn.edu OI Stupar, Robert/0000-0002-8836-2924 FU Minnesota Soybean Research and Promotion Council [667234-13-10CN]; U.S. Department of Agriculture-Agricultural Research Service [58-3640-0-626]; National Science Foundation [DBI 0923827]; National Institutes of Health [R01 GM088040, R01 GM069906, R24 GM078369, T32 CA009216] FX This work was supported by the Minnesota Soybean Research and Promotion Council (award no. 667234-13-10CN), the U.S. Department of Agriculture-Agricultural Research Service (agreement 58-3640-0-626), the National Science Foundation (award no. DBI 0923827), and the National Institutes of Health (award nos. R01 GM088040, R01 GM069906, R24 GM078369, and T32 CA009216). NR 38 TC 86 Z9 94 U1 5 U2 37 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD JUN PY 2011 VL 156 IS 2 BP 466 EP 473 DI 10.1104/pp.111.172981 PG 8 WC Plant Sciences SC Plant Sciences GA 771HC UT WOS:000291146800003 PM 21464476 ER PT J AU Craft, RO May, JW AF Craft, Randall O. May, James W., Jr. TI Staged Nipple Reconstruction with Vascularized SurgiMend Acellular Dermal Matrix SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter ID ALLODERM C1 [Craft, Randall O.; May, James W., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA. RP Craft, RO (reprint author), Harvard Plast Surg, Boston, MA 02115 USA. EM rcraft@partners.org NR 4 TC 10 Z9 10 U1 0 U2 3 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 JUN PY 2011 VL 127 IS 6 BP 148E EP 149E DI 10.1097/PRS.0b013e3182131e74 PG 2 WC Surgery SC Surgery GA 772DP UT WOS:000291212700011 PM 21617431 ER PT J AU Hartzell, TL Medina, M Hornicek, FJ Austen, WG AF Hartzell, Tristan L. Medina, Miguel Hornicek, Francis J. Austen, William G., Jr. TI Extended Dermal Apposition: A Simple Technique for the Closure of Irradiated Perineal and Sacral Wounds SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter C1 [Hartzell, Tristan L.; Medina, Miguel; Austen, William G., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Hornicek, Francis J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Hartzell, TL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 55 Fruit St, Boston, MA 02114 USA. EM thartzell@partners.org NR 5 TC 1 Z9 1 U1 0 U2 2 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 JUN PY 2011 VL 127 IS 6 BP 170E EP 173E DI 10.1097/PRS.0b013e318213a3e2 PG 4 WC Surgery SC Surgery GA 772DP UT WOS:000291212700025 PM 21617445 ER PT J AU Medina, MA Nguyen, JT Kirkham, JC Lee, JH McCormack, MC Randolph, MA Austen, WG AF Medina, Miguel A., III Nguyen, John T. Kirkham, John C. Lee, Jeffery H. McCormack, Michael C. Randolph, Mark A. Austen, William G., Jr. TI Polymer Therapy: A Novel Treatment to Improve Fat Graft Viability SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID RHEOTHRX INJECTION; MAMMALIAN-CELLS; POLOXAMER-188; LIPOSUCTION; INJURY; RECOVERY; CENTRIFUGATION; SURVIVAL; NECROSIS; HARVEST AB Background: Autologous fat grafting is currently undergoing a renaissance. However, fat grafts are limited by unpredictable survival. Poloxamers can act as tissue surfactants. These nonionic surfactants have been shown to stabilize the membranes of damaged cells and to protect against injury and apoptosis in numerous models. This study was designed to investigate the ability of poloxamers to protect harvested adipocytes and to increase fat graft survival. Methods: Lipoaspirate was obtained from surgical patients. Samples were washed in normal saline, centrifuged at 200 g, treated with various poloxamers or poloxamer components for 30 minutes, centrifuged at 200 g, and implanted into the flanks of nude mice in 1.0-cc, 1.0-g lobules. The grafts were explanted serially for 10 days and at 6 weeks. Endpoints were weight, apoptosis, cell viability, DNA content, and histology. Results: Grafts treated with poloxamers P188, F108, and F127 demonstrated increased graft survival by weight. Fat grafts treated with poloxamers L64 and P188 demonstrated improvement in cell viability, and those treated with poloxamers L64, P188, and F38 demonstrated improved histology. P188-treated grafts demonstrated a 50 percent reduction in apoptosis compared with saline-treated controls (p < 0.05) and an overall 72 percent survival by weight at 6 weeks. P188 demonstrated statistically significant improvement by weight, DNA content, histology, and cell viability (89 percent versus 33 percent). Conclusions: The authors demonstrate that poloxamers, with membrane-sealing capability, can increase graft survival. Among these poloxamers, P188 demonstrated statistically significant improvement in apoptosis, graft survival by weight, cell viability, DNA content, and histology. (Plast. Reconstr. Surg. 127: 2270, 2011.) C1 [Medina, Miguel A., III; Nguyen, John T.; Kirkham, John C.; Lee, Jeffery H.; McCormack, Michael C.; Randolph, Mark A.; Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Dept Surg, Boston, MA 02114 USA. RP Medina, MA (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Dept Surg, 55 Fruit St,Wang 435, Boston, MA 02114 USA. EM mamedina@partners.org FU Aesthetec Corporation FX This study was funded in part by a grant from Aesthetec Corporation (to W.G.A.). NR 46 TC 10 Z9 10 U1 0 U2 3 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 JUN PY 2011 VL 127 IS 6 BP 2270 EP 2282 DI 10.1097/PRS.0b013e3182139fc1 PG 13 WC Surgery SC Surgery GA 772DP UT WOS:000291212700044 PM 21617461 ER PT J AU Kruger, EA Im, DD Bischoff, DS Pereira, CT Huang, WB Rudkin, GH Yamaguchi, DT Miller, TA AF Kruger, Erwin A. Im, Daniel D. Bischoff, David S. Pereira, Clifford T. Huang, Weibiao Rudkin, George H. Yamaguchi, Dean T. Miller, Timothy A. TI In Vitro Mineralization of Human Mesenchymal Stem Cells on Three-Dimensional Type I Collagen versus PLGA Scaffolds: A Comparative Analysis SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CYCLIC TENSILE STRAIN; OSTEOGENIC DIFFERENTIATION; CHEMOKINE RECEPTORS; EXPRESSION; PROLIFERATION; HYPOXIA; STIMULATION; MATRICES; MIGRATE; CULTURE AB Background: Development of a tissue engineered bone graft requires efficient bioactivity screening of biomaterials in clinically relevant three-dimensional systems. The authors analyzed the relative osteogenic potential of two three-dimensional biomaterials-type I collagen and poly(L-lactide-co-glycolide) (PLGA)-to support in vitro mineralization of human mesenchymal stem cells. Methods: Human mesenchymal stem cells were seeded onto three-dimensional PLGA or type I collagen scaffolds; incubated in osteogenic media; and harvested at 1, 4, and 7 days. Messenger RNA expression was analyzed using quantitative real-time reverse-transcriptase polymerase chain reaction for osteogenic (i.e., alkaline phosphatase, osteocalcin, bone sialoprotein, Runx2/core binding factor alpha-1) and angiogenic (i.e., vascular endothelial growth factor and interleukin-8) markers. Alkaline phosphatase enzyme activity was measured at 4 and 7 days. Mineralization was detected by alizarin red staining and micro-computed tomographic imaging at 8 and 12 weeks. Mineral composition was analyzed by solid-phase nuclear magnetic resonance spectroscopy. Results: Early osteogenic and angiogenic markers, and alkaline phosphatase enzyme activity, were up-regulated on PLGA versus collagen scaffolds. However, long-term mineralization endpoints favored type I collagen. By 8 weeks, human mesenchymal stem cells on collagen exhibited significantly higher mineral density by micro-computed tomographic and alizarin red staining than PLGA scaffolds. Both biomaterials deposited calcium hydroxyapatite as determined by nuclear magnetic resonance spectroscopy. Conclusions: The authors' findings suggest that despite early PLGA induction of osteogenic gene expression, long-term mineralization occurs earlier and to a greater extent on type I collagen, highlighting collagen as a potential bone tissue engineering scaffold in the human mesenchymal stem cell niche. When screening the relative osteoinductive profiles of three-dimensional bone tissue engineering scaffolds in vitro, the authors recommend including long-term endpoints of osteogenesis. (Plast. Reconstr. Surg. 127: 2301, 2011.) C1 [Miller, Timothy A.] Vet Affairs Greater Los Angeles Healthcare Syst, Plast Surg Lab, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Plast & Reconstruct Surg, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Albert Einstein Coll Med, Bronx, NY USA. Harbor UCLA Med Ctr, Dept Surg, Torrance, CA USA. RP Miller, TA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Plast Surg Lab, Room 221,Bldg 114,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM tmiller@mednet.ucla.edu FU Veterans Affairs National Merit Review Grant FX This work was supported by a Veterans Affairs National Merit Review Grant awarded to Dr. Timothy Miller. The authors thank Nalini Makhijani of the Veterans Affairs Research Service for assistance in cell culture and Dr. Robert Taylor of the University of California, Los Angeles Department of Chemistry for assistance with nuclear magnetic resonance spectroscopy. NR 35 TC 14 Z9 14 U1 1 U2 12 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 JUN PY 2011 VL 127 IS 6 BP 2301 EP 2311 DI 10.1097/PRS.0b013e318213a004 PG 11 WC Surgery SC Surgery GA 772DP UT WOS:000291212700047 PM 21617464 ER PT J AU Singh, JA Sarkin, A Shieh, M Khanna, D Terkeltaub, R Lee, SJ Kavanaugh, A Hirsch, JD AF Singh, Jasvinder A. Sarkin, A. Shieh, M. Khanna, D. Terkeltaub, R. Lee, S. J. Kavanaugh, A. Hirsch, J. D. TI Health Care Utilization in Patients with Gout SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE health care utilization; gout; predictors; resource utilization; gout severity ID QUALITY-OF-LIFE; MEDICAL-RECORD; MYOCARDIAL-INFARCTION; SELF-REPORTS; SERUM URATE; ARTHRITIS; VALIDITY; COSTS; POPULATION; DISEASE AB Objective: To study health care utilization patterns in patients with gout. Methods: In a gout population from primary care and rheumatology clinics in 3 U.S. metropolitan cities, we collected data on gout-related utilization (primary care, rheumatology, urgent care, emergency room, and other) in the past year. We evaluated the association of comorbidities, age, gender, gout characteristics (time since last gout attack and tophi), and gout severity ratings (mean of serum uric acid, patient-rated, and physician-rated gout severity) and with emergency/urgent care and primary care utilization using regression and correlation analyses. Results: Of the 296 patients who reported visiting at least 1 type of health practitioner for gout in the past year, the percentage of patients utilizing the service at least once and annual utilization rates among utilizers were as follows: primary care physician, 60%, 3.0 +/- 3.4; nurse practitioner/physician assistant, 26%, 2.7 +/- 2.5; rheumatologist, 51%, 3.7 +/- 5.7; urgent care, 23%, 2.1 +/- 2.2; emergency room, 20%, 2.0 +/- 1.7; and hospitalization, 7%, 2.1 +/- 1.4. Higher overall gout severity was associated with greater use of each resource type and with overall gout-related utilization. Nonemergency/nonurgent care utilization (primary care physician, nurse practitioner, physician's assistant, and rheumatologist for gout) was the strongest predictor of gout-related emergency/urgent care utilization. Patients with more comorbidities had greater gout-related primary care utilization. Conclusions: Overall gout severity was associated with all types of gout-related utilization. This may help to screen high utilizers for targeted behavioral and therapeutic interventions. Having a higher number of comorbid conditions was a risk factor for higher gout-related primary care utilization. Published by Elsevier Inc. Semin Arthritis Rheum 40:501-511 C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL USA. [Sarkin, A.; Shieh, M.] Univ Calif San Diego, Hlth Serv Res Ctr, San Diego, CA 92103 USA. [Khanna, D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Terkeltaub, R.; Lee, S. J.; Kavanaugh, A.; Hirsch, J. D.] VA San Diego Healthcare Syst, San Diego, CA USA. [Hirsch, J. D.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Takeda Pharmaceutical Products, Inc; San Diego General Clinical Research Center [M01 RR00827]; National Center for Research Resources, National Institutes of Health; National Institutes of Health [NIAMS K23 AR053858-01A1, 1 KL2 RR024151-01]; VA Research Service; University of California; Department of Veterans Affairs; Arthritis Foundation; University of Minnesota; Cochrane centers; Minnesota Medical Foundation; Allergan; Takeda; Savient; Wyeth; Amgen; URL Pharmaceuticals; Novartis; TAP; Takeda pharmaceuticals; Regeneron; Research Service of the Department of Veterans Affairs FX This work was supported by the Takeda Pharmaceutical Products, Inc, VA Research Service and the University of California, San Diego General Clinical Research Center Program, M01 RR00827, National Center for Research Resources, National Institutes of Health. D.K. was also supported by a National Institutes of Health Award (NIAMS K23 AR053858-01A1) during this period. J.A.S. was supported by a National Institutes of Health CTSA Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research). R.T. was supported by the VA Research Service.; Disclosure Statement: J.A.S. has received speaker honoraria from Abbott, research grants from Department of Veterans Affairs, National Institutes of Health, Arthritis Foundation, University of Minnesota, Cochrane centers, Minnesota Medical Foundation, research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen and consultant fees from Savient, URL Pharmaceuticals, and Novartis. J.D.H. has received a research grant from TAP and Takeda pharmaceuticals and consultant fees from Regeneron. R.T. is a consultant for Takeda, Savient, EnzymeRx, Altus, BioCryst, Regeneron, Novartis, Pfizer, URL Pharma, and Proctor & Gamble and has received grants from the Research Service of the Department of Veterans Affairs and Takeda Pharmaceuticals. D.K. has received consultant fees and research grants from Takeda Pharmaceuticals. A.K. has received consultant fees from URL pharmaceuticals. All other authors have no conflicts of interest to disclose. NR 29 TC 21 Z9 21 U1 1 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 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD JUN PY 2011 VL 40 IS 6 BP 501 EP 511 DI 10.1016/j.semarthrit.2010.07.001 PG 11 WC Rheumatology SC Rheumatology GA 772ZZ UT WOS:000291278100002 PM 20828793 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Introduction: Current and Future Approaches to Chemotherapy in Patients With Resistant Breast Cancer SO SEMINARS IN ONCOLOGY LA English DT Editorial Material ID PHASE-II; RANDOMIZED-TRIAL; PACLITAXEL; CAPECITABINE; DOXORUBICIN; PLUS; ANTHRACYCLINE; COMBINATION; CONCOMITANT; DOCETAXEL C1 Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, 44 Binney St,Mayer 2, Boston, MA 02115 USA. EM hal_burstein@dfci.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2011 VL 38 IS 3 SU 2 BP S1 EP S2 DI 10.1053/j.seminoncol.2011.04.001 PG 2 WC Oncology SC Oncology GA 771PU UT WOS:000291174000001 PM 21600379 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Novel Agents and Future Directions for Refractory Breast Cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID CELLS; SRC; INHIBITION; DASATINIB; PATHWAYS; THERAPY; GROWTH C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02215 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM hal_burstein@dfci.harvard.edu FU Eisai, Inc. FX Publication of this article was supported by Eisai, Inc. NR 30 TC 21 Z9 23 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2011 VL 38 IS 3 SU 2 BP S17 EP S24 DI 10.1053/j.seminoncol.2011.04.002 PG 8 WC Oncology SC Oncology GA 771PU UT WOS:000291174000004 PM 21600381 ER PT J AU Xie, AL Bedekar, A Skatrud, JB Teodorescu, M Gong, YS Dempsey, JA AF Xie, Ailiang Bedekar, Ajay Skatrud, James B. Teodorescu, Mihaela Gong, Yuansheng Dempsey, Jerome A. TI The Heterogeneity of Obstructive Sleep Apnea (Predominant Obstructive vs Pure Obstructive Apnea) SO SLEEP LA English DT Article DE CO(2) reserve; Pcrit; OSA ID UPPER AIRWAY COLLAPSIBILITY; CONTROL MECHANISMS; RESPIRATORY DRIVE; NEGATIVE-PRESSURE; MUSCLE-ACTIVITY; PATHOGENESIS; RESISTANCE; STABILITY; INSTABILITY; THRESHOLD AB Study Objectives: To compare the breathing instability and upper airway collapsibility between patients with pure OSA (i.e. 100% of apneas are obstructive) and patients with predominant OSA (i.e., coexisting obstructive and central apneas). Design: A cross-sectional study with data scored by a fellow being blinded to the subjects' classification. The results were compared between the 2 groups with unpaired student t-test. Setting and interventions: Standard polysomnography technique was used to document sleep-wake state. Ventilator in pressure support mode was used to introduce hypocapnic apnea during CO(2) reserve measurement. CPAP with both positive and negative pressures was used to produce obstructive apnea during upper airway collapsibility measurement. Participants: 21 patients with OSA: 12 with coexisting central/mixed apneas and hypopneas (28% +/- 6% of total), and 9 had pure OSA. Measurements: The upper airway collapsibility was measured by assessing the critical closing pressure (Pcrit). Breathing stability was assessed by measuring CO(2) reserve (i.e.,Delta PCO(2) [eupnea-apnea threshold]) during NREM sleep. Results: There was no difference in Pcrit between the 2 groups (pure OSA vs. predominant OSA: 2.0 +/- 0.4 vs. 2.7 +/- 0.4 cm H(2)O, P = 0.27); but the CO(2) reserve was significantly smaller in predominant OSA group (1.6 +/- 0.7 mm Hg) than the pure OSA group (3.8 +/- 0.6 mm Hg) (P = 0.02). Conclusions: The present data indicate that breathing stability rather than upper airway collapsibility distinguishes OSA patients with a combination of obstructive and central events from those with pure OSA. C1 [Bedekar, Ajay; Skatrud, James B.; Teodorescu, Mihaela; Gong, Yuansheng] Univ Wisconsin, Dept Med, Madison, WI USA. [Xie, Ailiang; Skatrud, James B.; Teodorescu, Mihaela] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Xie, AL (reprint author), VA Hosp, Pulm Physiol Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. EM axie@wisc.edu FU VA Medical Research Service; American Lung Association of Wisconsin; NIH-NHLB1 [1RC1HL099724-01] FX We would like to thanks Dominic S. Puleo for technique assistance. Research work performed at Pulmonary Physiology Laboratory, VA Hospital, Madison, WI. This work was supported by the VA Medical Research Service; American Lung Association of Wisconsin; and NIH-NHLB1 (Grant 1RC1HL099724-01). NR 35 TC 15 Z9 15 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JUN 1 PY 2011 VL 34 IS 6 BP 745 EP 750 DI 10.5665/SLEEP.1040 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 771LE UT WOS:000291158000010 PM 21629362 ER PT J AU Siegel, JM AF Siegel, Jerome M. TI REM sleep: A biological and psychological paradox SO SLEEP MEDICINE REVIEWS LA English DT Editorial Material ID EYE-MOVEMENT SLEEP; IN-VIVO MICRODIALYSIS; LOCUS-COERULEUS; MEDIAL MEDULLA; BLOOD-PRESSURE; GABA RELEASE; CATAPLEXY; NEURONS; NARCOLEPSY; PONTINE C1 [Siegel, Jerome M.] Vet Adm Greater Los Angeles Healthcare Syst, Neurobiol Res 151A3, North Hills, CA 91343 USA. [Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Siegel, JM (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Neurobiol Res 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM JSiegel@ucla.edu FU BLRD VA [I01 BX001753]; NIDA NIH HHS [R01 DA034748]; NIMH NIH HHS [R01 MH064109, R01 MH064109-09]; NINDS NIH HHS [R01 NS014610-30, R01 NS014610, R01 NS069640, R01 NS069640-01] NR 58 TC 25 Z9 25 U1 3 U2 26 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1087-0792 J9 SLEEP MED REV JI Sleep Med. Rev. PD JUN PY 2011 VL 15 IS 3 BP 139 EP 142 DI 10.1016/j.smrv.2011.01.001 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 771QE UT WOS:000291175000001 PM 21482156 ER PT J AU Patel, VI Mukhopadhyay, S Aranson, NJ Ergul, E Schainfeld, R Conrad, MF Cambria, RP AF Patel, Virendra I. Mukhopadhyay, Shankha Aranson, Nathan J. Ergul, Emel Schainfeld, Robert Conrad, Mark F. Cambria, Richard P. TI Clinical outcomes of aortic reconstruction for vasculitis in the Medicare population (2004-2007) SO VASCULAR MEDICINE LA English DT Meeting Abstract C1 [Patel, Virendra I.; Mukhopadhyay, Shankha; Aranson, Nathan J.; Ergul, Emel; Schainfeld, Robert; Conrad, Mark F.; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD JUN PY 2011 VL 16 IS 3 MA 35 BP 235 EP 235 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 772FB UT WOS:000291218600043 ER PT J AU Campbell, J Prochazka, A Gopal, R AF Campbell, Jessica Prochazka, Allan Gopal, Ravi TI The Need for a Uniform Use of the Construct of Burnout Reply SO ACADEMIC MEDICINE LA English DT Letter ID PERCEIVED MEDICAL ERRORS; ASSOCIATION; DISTRESS C1 [Campbell, Jessica; Prochazka, Allan; Gopal, Ravi] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Campbell, Jessica] Denver Hlth Med Ctr, Div Hosp Med, Denver, CO USA. [Prochazka, Allan; Gopal, Ravi] Denver VA Med Ctr, Dept Ambulatory Care, Denver, CO USA. RP Campbell, J (reprint author), Univ Colorado, Denver Sch Med, Aurora, CO USA. EM jessica.campbell@dhha.org NR 7 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 2011 VL 86 IS 6 BP 661 EP 661 DI 10.1097/ACM.0b013e318218858f PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 769IM UT WOS:000291006100003 ER PT J AU Scott, DR Weimer, M English, C Shaker, L Ward, W Choi, D Cedfeldt, A Girard, D AF Scott, David R. Weimer, Melissa English, Clea Shaker, Lynn Ward, William Choi, Dongseok Cedfeldt, Andrea Girard, Donald TI A Novel Approach to Increase Residents' Involvement in Reporting Adverse Events SO ACADEMIC MEDICINE LA English DT Article ID IMPROVE PATIENT SAFETY; QUALITY IMPROVEMENT; MEDICAL ERRORS; TEACHING HOSPITALS; PHYSICIANS; EDUCATION AB Purpose In the wake of the Patient Safety and Quality Improvement Act of 2005, national attention has increasingly focused on adverse-event reporting as a means of identifying systems changes to improve patient safety. However, physicians and residents have demonstrated meager involvement in this effort. Method In 2008-2009, the authors measured participation in adverse-event reporting by 680 residents at Oregon Health & Science University before and after implementing a quality improvement initiative, which consisted of a financial incentive and multifaceted educational campaign. The primary measure of success was an increase in the average monthly adverse-event reports submitted by residents to greater than 5% of the institution's overall report submissions. Results The average number of adverse events reported by residents increased from 1.6% to 9.0% of the institution's overall event reports, representing a 5.6-fold increase during the initiative (P < .001). The relative percentage of resident-submitted reports defined as "near-misses" increased from 6% to 27% during the initiative (P < .001). Conclusions The novel approach of integrating a retirement benefit and educational campaign to increase residents' involvement in adverse-event reporting was successful. In addition to increasing residents' contributions to adverse-event reporting to levels higher than any documented in the current literature, there was also a remarkable increase in the relative frequency of near-miss reporting by residents. C1 [Scott, David R.; Weimer, Melissa] Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland, OR 97239 USA. [Scott, David R.] Portland VA Med Ctr, Dept Med, Portland, OR USA. [Ward, William] Mayo Clin, Dept Primary Care Internal Med, Rochester, MN USA. [Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Girard, Donald] Oregon Hlth & Sci Univ, Dept Grad & Continuing Med Educ, Portland, OR 97239 USA. RP Scott, DR (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, 3181 SW Sam Jackson Pk Rd,OP-30, Portland, OR 97239 USA. EM scottdav@ohsu.edu RI Ward, William/C-7052-2013 FU Oregon Health & Science University FX Salary support was obtained from Oregon Health & Science University. NR 16 TC 11 Z9 11 U1 9 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 2011 VL 86 IS 6 BP 742 EP 746 DI 10.1097/ACM.0b013e318217e12a PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 769IM UT WOS:000291006100026 PM 21512369 ER PT J AU Mimiaga, MJ Landers, SJ Conron, KJ AF Mimiaga, Matthew J. Landers, Stewart J. Conron, Kerith J. TI Prevalence and Correlates of Lifetime HIV Testing in a Population-Based Sample of Men Who Have Sex with Men in Massachusetts SO AIDS PATIENT CARE AND STDS LA English DT Letter ID RISK; BEHAVIORS; VIRUS C1 [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Sch Publ Hlth,Dept Epidemiol, Boston, MA 02114 USA. [Mimiaga, Matthew J.] Fenway Inst, Boston, MA USA. [Landers, Stewart J.] John Snow Inc, Boston, MA USA. [Conron, Kerith J.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Conron, Kerith J.] Northeastern Univ, Inst Urban Hlth Res, Boston, MA 02115 USA. RP Mimiaga, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Sch Publ Hlth,Dept Epidemiol, 1 Bowdoin Sq 7th Floor, Boston, MA 02114 USA. EM mmimiaga@partners.org NR 11 TC 4 Z9 4 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JUN PY 2011 VL 25 IS 6 BP 323 EP 326 DI 10.1089/apc.2011.0078 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 769LM UT WOS:000291015000001 PM 21612544 ER PT J AU Merkulova, M Hurtado-Lorenzo, A Hosokawa, H Zhuang, ZJ Brown, D Ausiello, DA Marshansky, V AF Merkulova, Maria Hurtado-Lorenzo, Andres Hosokawa, Hiroyuki Zhuang, Zhenjie Brown, Dennis Ausiello, Dennis A. Marshansky, Vladimir TI Aldolase directly interacts with ARNO and modulates cell morphology and acidic vesicle distribution SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE ADP-ribosylation factor nucleotide site opener; vacuolar H(+)-ATPase; a-subunit isoforms; actin cytoskeleton; gelsolin; surface plasmon resonance; endosomal/lysosomal compartments ID VACUOLAR H+-ATPASE; NUCLEOTIDE-EXCHANGE FACTORS; YEAST V-ATPASE; PH DOMAIN; FRUCTOSE-1,6-BISPHOSPHATE ALDOLASE; ACTIN CYTOSKELETON; EPITHELIAL-CELLS; PROXIMAL TUBULE; EARLY ENDOSOMES; SUBUNIT GENES AB Merkulova M, Hurtado-Lorenzo A, Hosokawa H, Zhuang Z, Brown D, Ausiello DA, Marshansky V. Aldolase directly interacts with ARNO and modulates cell morphology and acidic vesicle distribution. Am J Physiol Cell Physiol 300: C1442-C1455, 2011. First published February 9, 2011; doi: 10.1152/ajpcell.00076.2010.-Previously, we demonstrated that the vacuolar-type H(+)-ATPase (V-ATPase) a2-subunit functions as an endosomal pH sensor that interacts with the ADP-ribosylation factor (Arf) guanine nucleotide exchange factor, ARNO. In the present study, we showed that ARNO directly interacts not only with the a2-subunit but with all a-isoforms (a1-a4) of the V-ATPase, indicating a widespread regulatory interaction between V-ATPase and Arf GTPases. We then extended our search for other ARNO effectors that may modulate V-ATPase-dependent vesicular trafficking events and actin cytoskeleton remodeling. Pull-down experiments using cytosol of mouse proximal tubule cells (MTCs) showed that ARNO interacts with aldolase, but not with other enzymes of the glycolytic pathway. Direct interaction of aldolase with the pleckstrin homology domain of ARNO was revealed by pull-down assays using recombinant proteins, and surface plasmon resonance revealed their high avidity interaction with a dissociation constant: K(D) = 2.84 x 10(-10) M. MTC cell fractionation revealed that aldolase is also associated with membranes of early endosomes. Functionally, aldolase knockdown in HeLa cells produced striking morphological changes accompanied by long filamentous cell protrusions and acidic vesicle redistribution. However, the 50% knockdown we achieved did not modulate the acidification capacity of endosomal/lysosomal compartments. Finally, a combination of small interfering RNA knockdown and overexpression revealed that the expression of aldolase is inversely correlated with gelsolin levels in HeLa cells. In summary, we have shown that aldolase forms a complex with ARNO/Arf6 and the V-ATPase and that it may contribute to remodeling of the actin cytoskeleton and/or the trafficking and redistribution of V-ATPase-dependent acidic compartments via a combination of protein-protein interaction and gene expression mechanisms. C1 [Marshansky, Vladimir] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Simches Res Ctr, Boston, MA 02114 USA. [Marshansky, Vladimir] Massachusetts Gen Hosp, Div Nephrol, Ctr Syst Biol, Simches Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Marshansky, V (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Simches Res Ctr, 185 Cambridge St,CPZN,Suite 8212, Boston, MA 02114 USA. EM Vladimir_Marshansky@hms.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK038452]; Boston Area Diabetes Research Center NIDDK [DK057521-08] FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant DK038452 (to V. Marshansky, D. Brown, and D. A. Ausiello) and a pilot and feasibility study supported by a Boston Area Diabetes Research Center NIDDK Grant DK057521-08 (to V. Marshansky). NR 75 TC 25 Z9 25 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUN PY 2011 VL 300 IS 6 BP C1442 EP C1455 DI 10.1152/ajpcell.00076.2010 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 769LY UT WOS:000291016400026 PM 21307348 ER PT J AU Wang, XR Zhang, MW Chen, DD Zhang, Y Chen, AF AF Wang, Xiao-Rong Zhang, Ming-Wei Chen, Dan-Dan Zhang, Yun Chen, Alex F. TI AMP-activated protein kinase rescues the angiogenic functions of endothelial progenitor cells via manganese superoxide dismutase induction in type 1 diabetes SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE protein phosphatase 2A; angiogenesis; oxidase stress ID SUPPRESSING OXIDATIVE STRESS; NITRIC-OXIDE SYNTHASE; VASCULAR COMPLICATIONS; SKELETAL-MUSCLE; UP-REGULATION; HYPERTENSION; EXPRESSION; MICE; DIFFERENTIATION; VASCULOPATHY AB Endothelial progenitor cells (EPCs) play an essential role in angiogenesis but are functionally impaired in diabetes. We recently reported that decreased expression of manganese superoxide dismutase (MnSOD) critically contributes to diabetic EPC dysfunction. AMP-activated protein kinase (AMPK) activation has been shown to induce MnSOD and suppress hyperglycemia-induced mitochondrial ROS production in endothelial cells. However, whether AMPK protects EPCs from oxidative stress in diabetes is unknown. We tested the hypothesis that AMPK activation rescues impaired EPC functions through MnSOD induction in type 1 diabetes. Bone marrow-derived EPCs from adult male streptozotocin-induced diabetic mice and normal controls were used. AMPK activity was decreased in diabetic EPCs, indicated by reduced AMPK and acetyl-CoA carboxylase phosphorylation. AMPK activation by treating diabetic EPCs with its selective agonist AICAR rescued their in vitro functions, including Matrigel tube formation, adhesion, and migration. Furthermore, AICAR restored the decreased MnSOD protein and enzymatic activity and suppressed the mitochondrial superoxide level in diabetic EPCs, indicated by MitoSOX flow cytometry. These beneficial effects of AICAR on MnSOD and EPC functions were significantly attenuated by silencing MnSOD or AMPK antagonist compound C pretreatment. Finally, the expression of protein phosphatase 2A, a key enzyme for AMPK dephosphorylation and inactivation, was increased in diabetic EPCs, and its inhibition by siRNA or okadaic acid reversed the deficient AMPK activation and MnSOD level in diabetic EPCs. These findings demonstrate for the first time that AMPK activation rescues impaired EPC functions and suppresses mitochondrial superoxide by inducing MnSOD in type 1 diabetes. C1 [Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Vasc Med Inst,McGowan Inst Regenerat Med, Pittsburgh, PA 15213 USA. [Wang, Xiao-Rong; Zhang, Ming-Wei; Zhang, Yun] Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ, Dept Cardiol,Qilu Hosp, Jinan 250100, Peoples R China. [Wang, Xiao-Rong; Zhang, Ming-Wei; Zhang, Yun] Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Publ Hlth, Dept Cardiol,Qilu Hosp, Jinan 250100, Peoples R China. [Wang, Xiao-Rong; Zhang, Ming-Wei; Chen, Dan-Dan; Chen, Alex F.] Vet Affairs Pittsburgh Healthcare Syst, Vasc Surg Res, Pittsburgh, PA USA. RP Chen, AF (reprint author), Univ Pittsburgh, Sch Med, Dept Surg, Vasc Med Inst,McGowan Inst Regenerat Med, W1148 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. EM chena5@upmc.edu FU National Institute of General Medical Science [R01 GM-077352]; American Diabetes Association [7-08-RA-23]; American Heart Association [09POST2370060] FX This work was funded by Grant R01 GM-077352 from the National Institute of General Medical Science; Grant 7-08-RA-23 from the American Diabetes Association (to A. F. Chen). X. R. Wang is the recipient of an American Heart Association postdoctoral fellowship award (09POST2370060). NR 42 TC 31 Z9 33 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2011 VL 300 IS 6 BP E1135 EP E1145 DI 10.1152/ajpendo.00001.2011 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 768SP UT WOS:000290959000021 PM 21427411 ER PT J AU Haastrup, AA Mendez, P Cote, CJ AF Haastrup, Adeniran A. Mendez, Pedro Cote, Charles J. TI Suction the Tongue: A New Adjunct for Improving the Laryngeal View for Fiberoptic Intubation SO ANESTHESIA AND ANALGESIA LA English DT Letter C1 [Haastrup, Adeniran A.; Mendez, Pedro; Cote, Charles J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol,Shriners Hosp Children, Boston, MA 02115 USA. RP Haastrup, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol,Shriners Hosp Children, Boston, MA 02115 USA. EM ahaastrup@partners.org NR 4 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 2011 VL 112 IS 6 BP 1512 EP 1513 DI 10.1213/ANE.0b013e318215c905 PG 4 WC Anesthesiology SC Anesthesiology GA 768TL UT WOS:000290961200049 PM 21613205 ER PT J AU Crosby, G Culley, DJ Hyman, BT AF Crosby, Gregory Culley, Deborah J. Hyman, Bradley T. TI Preoperative Cognitive Assessment of the Elderly Surgical Patient A Call for Action SO ANESTHESIOLOGY LA English DT Editorial Material ID NONCARDIAC SURGERY; CARDIAC-SURGERY; DYSFUNCTION; IMPAIRMENT; DELIRIUM; DISEASE; ILLNESS C1 [Crosby, Gregory; Culley, Deborah J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Hyman, Bradley T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Charlestown, MA USA. [Hyman, Bradley T.] Alzheimer Dis Res Ctr, Charlestown, MA USA. RP Crosby, G (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. EM gcrosby@zeus.bwh.harvard.edu FU NIA NIH HHS [P50 AG005134, P50 AG005134-29]; NIGMS NIH HHS [GM088817, K08 GM077057, K08 GM077057-05, R01 GM088817, R01 GM088817-08] NR 17 TC 20 Z9 20 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 2011 VL 114 IS 6 BP 1265 EP 1268 DI 10.1097/ALN.0b013e31821b1bc8 PG 4 WC Anesthesiology SC Anesthesiology GA 768PM UT WOS:000290947500003 PM 21490501 ER PT J AU Gadikota, HR Seon, JK Chen, CH Wu, JL Gill, TJ Li, GA AF Gadikota, Hemanth R. Seon, Jong Keun Chen, Chih-Hui Wu, Jia-Lin Gill, Thomas J. Li, Guoan TI In Vitro and Intraoperative Laxities After Single-Bundle and Double-Bundle Anterior Cruciate Ligament Reconstructions SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID PATELLAR TENDON-BONE; NAVIGATED ACL RECONSTRUCTION; PIVOT-SHIFT; BIOMECHANICAL ANALYSIS; HAMSTRING TENDON; JOINT KINEMATICS; TIBIAL ROTATION; STABILITY; KNEE; GRAFT AB Purpose: The purpose of this study was to objectively evaluate whether double-bundle anterior cruciate ligament (ACL) reconstruction can better restore the normal translational and rotational laxities than the conventional single-bundle ACL reconstruction among the reported biomechanical studies. Methods: A systematic literature search was conducted to identify in vitro and in vivo (intraoperative) biomechanical studies that compared the laxities (anterior or anteroposterior or rotational) between single-and double-bundle ACL reconstructions. Because of large variability among the loading conditions and testing methods used to determine the rotational laxities among the studies, a meta-analysis of rotational laxities was not feasible. Results: Seven in vitro and three in vivo studies were included in this analysis based on the predefined inclusion criteria. The overall mean differences calculated by the random effects model in anteroposterior laxity between the single-bundle and double-bundle ACL reconstruction techniques at 0 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion were 0.99 mm, 0.38 mm, 0.34 mm, and 0.07 mm, respectively. No statistically significant difference was noted between the 2 treatments at all flexion angles. Among the 9 studies that compared the rotational laxity of single-bundle and double-bundle ACL reconstructions, 4 reported that double-bundle reconstruction can provide better rotational control than single-bundle reconstruction. The other 5 studies could not identify any significant difference between the 2 reconstructions in terms of rotational laxity. Conclusions: Both single-and double-bundle treatment options for ACL injury result in similar anteroposterior knee joint laxity at time 0. No conclusive evidence on the superiority of 1 reconstruction technique over the other in terms of rotation laxity can be obtained because of several variations in the experimental protocol and the kinematics used to measure the rotational laxity among the studies. Level of Evidence: Level III, meta-analysis. C1 [Gadikota, Hemanth R.; Seon, Jong Keun; Chen, Chih-Hui; Wu, Jia-Lin; Gill, Thomas J.; Li, Guoan] Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. [Gadikota, Hemanth R.; Seon, Jong Keun; Chen, Chih-Hui; Wu, Jia-Lin; Gill, Thomas J.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Seon, Jong Keun] Chonnam Natl Univ, Dept Orthopaed, Hwasun Hosp, Jeonnam, South Korea. [Chen, Chih-Hui] Taichung Vet Gen Hosp, Dept Orthopaed Surg, Taichung, Taiwan. [Wu, Jia-Lin] Natl Def Med Ctr, Dept Orthopaed Surg, Tri Serv Gen Hosp, Taipei, Taiwan. RP Li, GA (reprint author), Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institutes of Health [R01AR055612] FX Supported by National Institutes of Health Grant No. R01AR055612. The authors report no conflict of interest. NR 46 TC 13 Z9 18 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD JUN PY 2011 VL 27 IS 6 BP 849 EP 860 DI 10.1016/j.arthro.2010.12.003 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 769WB UT WOS:000291047900019 PM 21624681 ER PT J AU Badr, CE Wurdinger, T Tannous, BA AF Badr, Christian E. Wurdinger, Thomas Tannous, Bakhos A. TI Functional Drug Screening Assay Reveals Potential Glioma Therapeutics SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES LA English DT Article ID TRAIL-INDUCED APOPTOSIS; STEM-CELLS; IN-VIVO; LUCIFERASE; CANCER; EXPRESSION; RESISTANCE; INHIBITOR; VARIANT; MODELS AB Here we describe a novel functional screening assay based on bioluminescence monitoring of the naturally secreted Gaussia luciferase (Gluc) in the conditioned medium of cultured cells. Using this assay, we identified small-molecule drugs that sensitized brain tumor cells to the tumor necrosis factor-related apoptosis-inducing ligand-induced cell death. Human glioblastoma multiforme cells were engineered by gene transfer to express Gluc as a reporter for cell viability, which can be monitored over time by bioluminescence measurements using a plate luminometer. We have optimized the Gluc assay for screening and validated it using the National Institute of Neurological Disorders and Stroke (NINDS) custom collection II library consisting of 1,040 drugs and bioactive compounds, most of which are Food and Drug Administration-approved and are able to cross the blood-brain barrier. We found that the cardiac glycosides family sensitized glioblastoma multiforme cells to the tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. In conclusion, the Gluc secretion assay is a robust tool for functional drug screening and can be applied to many different fields including cancer. C1 [Badr, Christian E.; Wurdinger, Thomas; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Boston, MA 02129 USA. [Badr, Christian E.; Wurdinger, Thomas; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Badr, Christian E.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Wurdinger, Thomas; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp E, Ctr Neurosci, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU National Institutes of Health/National Cancer Institute [4R00CA126839]; National Institutes of Health/National Institute of Neurological Disorders and Stroke [1R21NS061051, NS045776, 1R01NS064983]; American Brain Tumor Association; Executive Committee on Research at Massachusetts General Hospital FX The authors thank Dr. Robert Carter for providing the tumor tissue sections from GBM patients, Dr. Johan Skog for dissociation of these cells, and Mrs. Jorien Koelen for technical help. The authors are grateful to Dr. Xandra Breakefield for her significant input on this work and Drs. Hang Lee and Patrick Sluss for statistical analysis guidance. This work was supported by grants from the National Institutes of Health/National Cancer Institute (4R00CA126839), National Institutes of Health/National Institute of Neurological Disorders and Stroke (1R21NS061051, NS045776, and 1R01NS064983 to B. A. T.), the American Brain Tumor Association (to T. W.), Executive Committee on Research at Massachusetts General Hospital (to C.B.). NR 26 TC 13 Z9 13 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-658X J9 ASSAY DRUG DEV TECHN JI ASSAY DRUG DEV. TECHNOL. PD JUN PY 2011 VL 9 IS 3 BP 281 EP 289 DI 10.1089/adt.2010.0324 PG 9 WC Biochemical Research Methods; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 769LD UT WOS:000291014100006 PM 21184646 ER PT J AU Richardson, PG Chanan-Khan, AA Lonial, S Krishnan, AY Carroll, MP Alsina, M Albitar, M Berman, D Messina, M Anderson, KC AF Richardson, Paul G. Chanan-Khan, Asher A. Lonial, Sagar Krishnan, Amrita Y. Carroll, Michael P. Alsina, Melissa Albitar, Maher Berman, David Messina, Marianne Anderson, Kenneth C. TI Tanespimycin and bortezomib combination treatment in patients with relapsed or relapsed and refractory multiple myeloma: results of a phase 1/2 study SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE tanespimycin; bortezomib; myeloma; heat shock protein 90; proteasome ID CANCER STATISTICS; DOSE-ESCALATION; ADULT PATIENTS; SOLID TUMORS; I TRIAL; INHIBITION; HSP90; 17-(ALLYLAMINO)-17-DEMETHOXYGELDANAMYCIN; KOS-953; THERAPY AB P>This open-label, dose escalation, multicentre phase 1/2 trial was undertaken to determine the safety and tolerability of the heat shock protein 90 (HSP90) inhibitor tanespimycin (100-340 mg/m2) + bortezomib (0 center dot 7-1 center dot 3 mg/m2) given on days 1, 4, 8 and 11 in each 21-d cycle. Phase 2 expansion occurred at the highest tested dose of tanespimycin at 340 mg/m2 and bortezomib at 1 center dot 3 mg/m2. Seventy-two patients (median age, 60 years) with relapsed or relapsed and refractory multiple myeloma (MM) were enrolled; 63 patients (89%) completed the study. Tanespimycin in combination with bortezomib was well tolerated; few patients experienced significant neutropenia, constipation and anorexia (< 10%), and no patients developed severe peripheral neuropathy. Among 67 efficacy-evaluable patients, there were 2 (3%) complete responses and 8 (12%) partial responses, for an objective response rate (ORR) of 27%, including 8 (12%) minimal responses. Response rates were highest among bortezomib-naive patients and proved durable in all patient subgroups, including those with bortezomib-refractory disease. Pharmacodynamic analyses indicated that tanespimycin plus bortezomib effectively inhibited the proteasome, as evidenced by decreased 20S proteasome activity, and inhibited HSP90, as reflected by increased HSP70 expression. The results of this study support additional studies of this combination approach in MM. C1 [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chanan-Khan, Asher A.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Krishnan, Amrita Y.] City Hope Natl Med Ctr, Duarte, CA USA. [Carroll, Michael P.] Sutter Reg Canc Inst, Sacramento, CA USA. [Alsina, Melissa] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Albitar, Maher] Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA. [Berman, David] Bristol Myers Squibb Co, Princeton, NJ USA. [Messina, Marianne] Bristol Myers Squibb Co, Res & Dev, Wallingford, CT 06492 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu FU Bristol-Myers Squibb (Kosan Biosciences); Millennium Pharmaceuticals; Celgene Corporation; Novartis; Bristol-Myers Squibb; Gloucester Pharmaceuticals; Facet Biotech; Centocor Ortho Biotech Inc. FX The authors would like to thank the research nurses, physicians, coordinators, and other staff at the Dana-Farber Cancer Institute; Roswell Park Cancer Institute; Emory University, The Winship Cancer Institute; City of Hope; Sutter Regional Cancer Institute; H. Lee Moffitt Cancer Center; and Quest Diagnostics Nichols Institute. The authors would also like to thank Alison L. Hannah, MD, consultant, for her contributions to the study and study design, as well as Bindu Murthy, PharmD. The authors are most grateful to Monica Nicosia, PhD, Mary Dominiecki, PhD, Anne Lambert, MS, Robert O'Beirne, Andrew Graham, Katie Rogers, and Ted Everson, PhD for graphics and editorial assistance, and Katie Redman for administrative assistance in the preparation of this manuscript. Finally, we would especially like to thank the patients and their families for their participation. This study was sponsored by Bristol-Myers Squibb (and previously Kosan Biosciences).; Dr. Richardson serves on advisory boards to Millennium Pharmaceuticals, Inc., Celgene Corporation, Johnson & Johnson, Novartis, and Bristol-Myers Squibb. Dr. Chanan-Khan is on the speakers' bureaus and receives honoraria from Celgene Corporation, ImmunoGen, Inc., and Millennium Pharmaceuticals. Dr. Lonial is a consultant for Millennium Pharmaceuticals, Celgene Corporation, Novartis, Bristol-Myers Squibb, and Facet Biotech.* He has received research funding from Millennium Pharmaceuticals, Celgene Corporation, Novartis, Bristol-Myers Squibb, Gloucester Pharmaceuticals, and Facet Biotech.* Dr. Krishnan is on the speakers bureaus for Millennium Pharmaceuticals and Celgene Corporation, and is a consultant for Celgene Corporation. Dr. Alsina has received commercial research grants from Millennium Pharmaceuticals and Centocor Ortho Biotech Inc., and is a consultant for Millennium Pharmaceuticals and Celgene Corporation. Drs. Carroll and Albitar have no relevant conflicts of interest to disclose. Dr. Berman and Ms. Messina are employees of Bristol-Myers Squibb and have no relevant conflicts of interest to disclose. Dr. Anderson is a consultant for Celgene Corporation, Novartis, Millennium Pharmaceuticals, and Bristol-Myers Squibb. He receives research funding from Celgene Corporation, Novartis, Millennium Pharmaceuticals, and Bristol-Myers Squibb, and he has received honoraria from Celgene Corporation, Novartis, Millennium Pharmaceuticals, and Bristol-Myers Squibb. *Facet Biotech is now Abbott Biotherapeutics Corp. NR 31 TC 61 Z9 66 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2011 VL 153 IS 6 BP 729 EP 740 DI 10.1111/j.1365-2141.2011.08664.x PG 12 WC Hematology SC Hematology GA 769UR UT WOS:000291044300005 PM 21534941 ER PT J AU Sacks, DB Arnold, M Bakris, GL Bruns, DE Horvath, AR Kirkman, MS Lernmark, A Metzger, BE Nathan, DM AF Sacks, David B. Arnold, Mark Bakris, George L. Bruns, David E. Horvath, Andrea Rita Kirkman, M. Sue Lernmark, Ake Metzger, Boyd E. Nathan, David M. TI Executive Summary: Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus SO CLINICAL CHEMISTRY LA English DT Editorial Material ID US AB BACKGROUND: Multiple laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. APPROACH: An expert committee compiled evidence-based recommendations for the use of laboratory analysis in patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. A draft of the guidelines was posted on the Internet, and the document was modified in response to comments. The guidelines were reviewed by the joint Evidence-Based Laboratory Medicine Committee of the AACC and the National Academy of Clinical Biochemistry and were accepted after revisions by the Professional Practice Committee and subsequent approval by the Executive Committee of the American Diabetes Association. CONTENT: In addition to the long-standing criteria based on measurement of venous plasma glucose, diabetes can be diagnosed by demonstrating increased hemoglobin A(1c) (Hb A(1c)) concentrations in the blood. Monitoring of glycemic control is performed by the patients measuring their own plasma or blood glucose with meters and by laboratory analysis of Hb A(1c). The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. SUMMARY: The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended. (C) 2011 American Association for Clinical Chemistry and American Diabetes Association C1 [Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Arnold, Mark] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. [Bakris, George L.] Univ Chicago, Dept Med, Hypertens Dis Unit, Sect Endocrinol Diabet & Metab, Chicago, IL 60637 USA. [Bruns, David E.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. [Horvath, Andrea Rita] Univ Sydney, Screening & Test Evaluat Program, Sch Publ Hlth, SEALS Dept Clin Chem,Prince Wales Hosp, Sydney, NSW 2006, Australia. [Kirkman, M. Sue] Amer Diabet Assoc, Alexandria, VA USA. [Lernmark, Ake] Lund Univ, Dept Clin Sci, CRC, Skane Univ Hosp Malmo, Malmo, Sweden. [Metzger, Boyd E.] Northwestern Univ, Div Endocrinol, Feinberg Sch Med, Chicago, IL 60611 USA. [Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nathan, David M.] Harvard Univ, Sch Med, Ctr Diabet, Boston, MA USA. RP Sacks, DB (reprint author), NIH, Dept Lab Med, 10 Ctr Dr,Bldg 10,Rm 2C306, Bethesda, MD 20892 USA. EM sacksdb@mail.nih.gov OI Sacks, David/0000-0003-3100-0735 NR 8 TC 43 Z9 44 U1 1 U2 6 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 JUN PY 2011 VL 57 IS 6 BP 793 EP 798 DI 10.1373/clinchem.2011.163634 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 769PF UT WOS:000291028600002 PM 21617153 ER PT J AU Sacks, DB Arnold, M Bakris, GL Bruns, DE Horvath, AR Kirkman, MS Lernmark, A Metzger, BE Nathan, DM AF Sacks, David B. Arnold, Mark Bakris, George L. Bruns, David E. Horvath, Andrea Rita Kirkman, M. Sue Lernmark, Ake Metzger, Boyd E. Nathan, David M. TI Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus SO CLINICAL CHEMISTRY LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; POINT-OF-CARE; NUTRITION EXAMINATION SURVEY; RANDOMIZED CONTROLLED-TRIAL; IMPAIRED FASTING GLUCOSE; GENOME-WIDE ASSOCIATION; ANTIBODY STANDARDIZATION PROGRAM; PROTEIN-TYROSINE-PHOSPHATASE; HEMOGLOBIN A(1C) MEASUREMENT; COST-EFFECTIVENESS ANALYSIS AB BACKGROUND: Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially. APPROACH: An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. Draft guidelines were posted on the Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modified in response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence Based Laboratory Medicine Committee of the AACC jointly reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee and subsequently approved by the Executive Committee of the American Diabetes Association. CONTENT: In addition to long-standing criteria based on measurement of plasma glucose, diabetes can be diagnosed by demonstrating increased blood hemoglobin A(1c) (Hb A(1c)) concentrations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood glucose with meters and by laboratory analysis of Hb A(1c). The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. SUMMARY: The guidelines provide specific recommendations that are based on published data or derived from expert consensus. Several analytes have minimal clinical value at present, and their measurement is not recommended. (C) 2011 American Association for Clinical Chemistry and American Diabetes Association C1 [Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Arnold, Mark] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. [Bakris, George L.] Univ Chicago, Dept Med, Hypertens Dis Unit, Sect Endocrinol Diabet & Metab, Chicago, IL 60637 USA. [Bruns, David E.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. [Horvath, Andrea Rita] Univ Sydney, Sch Publ Hlth, Screening & Test Evaluat Program, SEALS Dept Clin Chem,Prince Wales Hosp, Sydney, NSW 2006, Australia. [Kirkman, M. Sue] Amer Diabet Assoc, Alexandria, VA USA. [Lernmark, Ake] Lund Univ, CRC, Skane Univ Hosp Malmo, Dept Clin Sci, Malmo, Sweden. [Metzger, Boyd E.] Northwestern Univ, Feinberg Sch Med, Div Endocrinol, Chicago, IL 60611 USA. [Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nathan, David M.] Harvard Univ, Sch Med, Ctr Diabet, Boston, MA USA. RP Sacks, DB (reprint author), NIH, Dept Lab Med, 10 Ctr Dr,Bldg 10,Rm 2C306, Bethesda, MD 20892 USA. EM sacksdb@mail.nih.gov OI Sacks, David/0000-0003-3100-0735 FU GlaxoSmithKline; Forest Laboratories; Novartis; PepsiCo; Abbott Diagnostics; Siemens; NIH; Partnership for Clean Competition FX G.L. Bakris, GlaxoSmithKline, Forest Laboratories, Novartis, and PepsiCo; D.E. Bruns, Abbott Diagnostics, Siemens, NIH, and Partnership for Clean Competition. NR 381 TC 140 Z9 148 U1 2 U2 35 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2011 VL 57 IS 6 BP E1 EP E47 DI 10.1373/clinchem.2010.161596 PG 47 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 769PF UT WOS:000291028600001 PM 21617152 ER PT J AU Zheng, H Nathan, DM Schoenfeld, DA AF Zheng, Hui Nathan, David M. Schoenfeld, David A. TI Using A Multi-Level B-Spline Model to Analyze and Compare Patient Glucose Profiles Based on Continuous Monitoring Data SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID REAL-TIME; PENALTIES AB Objective: We show how continuous glucose monitoring (CGM) data can be analyzed using a three-level B-spline model, facilitating the estimation of inter-patient variability, within-patient inter-day variability, and measurement error. We propose methods for statistical comparison of glucose profiles among patient groups. Methods: We applied a three-level random effects model using quadratic B-spline functions to analyze inter-patient and within-patient inter-day variations of the glucose trend. The estimated SD values of the glucose curves are time-dependent and were averaged over a 24-h period. We analyzed CGM data from 322 patients with type 1 diabetes, 223 patients with type 2 diabetes, and 86 subjects without diabetes using interstitial glucose levels measured every 5 min, for approximately 8 days per patient. We compared group-wide glucose profiles from the insulin pump-treated (n = 124) and multiple daily injection (MDI)-treated (n = 144) patients with type 1 diabetes. Results: The average inter-patient SD values were 49 mg/dL, 43 mg/dL, and 15 mg/dL for type 1 diabetes patients, type 2 diabetes patients, and subjects without diabetes, respectively. The average within-patient, inter-day SD values were 67 mg/dL, 41 mg/dL, and 18 mg/dL, respectively. The residual SD values were 19 mg/dL, 14 mg/dL, and 8 mg/dL, respectively. We identified a statistically significant difference in glucose profiles during the morning between insulin pump-treated and MDI-treated type 1 diabetes patients. Conclusions: B-spline models facilitate the analysis of CGM data and show that type 1 diabetes is associated with higher inter-day glucose variation than type 2 diabetes or being without diabetes. Pump therapy and MDI have different effects on glucose control during specific time periods. C1 [Zheng, Hui; Schoenfeld, David A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02446 USA. [Zheng, Hui; Nathan, David M.; Schoenfeld, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02446 USA. RP Zheng, H (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 5th Floor,Suite 560,50 Staniford St, Boston, MA 02446 USA. EM hzheng1@partners.org FU Massachusetts General Hospital; Harvard Catalyst; Harvard Clinical and Translational Science Center (National Institutes of Health) [UL1 RR 025758]; Harvard University; American Diabetes Association [7-06-A1C-11]; European Association for the Study of Diabetes; Abbott Diabetes Care; Bayer Healthcare; GlaxoSmithKline; Sanofi-Aventis Netherlands; Merck Company; Lifescan, Inc.; Medtronic MiniMed FX Support for the current analyses was provided by the Charlton Fund for Innovative Diabetes Research at Massachusetts General Hospital and from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Institutes of Health Award number UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). ADAG was supported by research grants from the American Diabetes Association (7-06-A1C-11) and the European Association for the Study of Diabetes. Financial support for ADAG was provided by Abbott Diabetes Care, Bayer Healthcare, GlaxoSmithKline, Sanofi-Aventis Netherlands, Merck & Company, Lifescan, Inc., and Medtronic MiniMed, and supplies and equipment were provided by Medtronic MiniMed, Lifescan, Inc., and Hemocue. A complete listing of the ADAG Research Group can be found in Nathan et al.9 The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, the National Institutes of Health, or the ADAG Research Group. NR 19 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JUN PY 2011 VL 13 IS 6 BP 675 EP 682 DI 10.1089/dia.2010.0199 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 769JP UT WOS:000291009000012 PM 21488799 ER PT J AU Kim, Y Mylonakis, E AF Kim, Younghoon Mylonakis, Eleftherios TI Killing of Candida albicans Filaments by Salmonella enterica Serovar Typhimurium Is Mediated by sopB Effectors, Parts of a Type III Secretion System SO EUKARYOTIC CELL LA English DT Article ID BIOFILM FORMATION; CAENORHABDITIS-ELEGANS; ESCHERICHIA-COLI; STREPTOCOCCUS-GORDONII; QUANTITATIVE PCR; EPITHELIAL-CELLS; GENE-EXPRESSION; HYPHAL GROWTH; HOST-CELLS; PROTEIN AB Although bacterial-fungal interactions shape microbial virulence during polymicrobial infections, only a limited number of studies have evaluated this interaction on a genetic level. We report here that one interaction is mediated by sopB, an effector of a type III secretion system (TTSS) of Salmonella enterica serovar Typhimurium. In these studies, we screened 10 TTSS effector-related mutants and determined their role in the killing of C. albicans filaments in vitro during coinfection in planktonic environments. We found that deleting the sopB gene (which encodes inositol phosphatase) was associated with a significant decrease in C. albicans killing at 25 degrees C after 5 days, similar to that caused by the deletion of sipB (which encodes TTSS translocation machinery components). The sopB deletion dramatically influenced the killing of C. albicans filaments. It was associated with repressed filamentation in the Caenorhabditis elegans model of C. albicans-S. Typhimurium coinfection, as well as with biofilm formation by C. albicans. We confirmed that SopB translocated to fungal filaments through SipB during coinfection. Using quantitative real-time PCR assays, we found that the Candida supernatant upregulated the S. Typhimurium genes associated with C. albicans killing (sopB and sipB). Interestingly, the sopB effector negatively regulated the transcription of CDC42, which is involved in fungal viability. Taken together, these results indicate that specific TTSS effectors, including SopB, play a critical role in bacterial-fungal interactions and are important to S. Typhimurium in order to selectively compete with fungal pathogens. These findings highlight a new role for TTSS of S. Typhimurium in the intestinal tract and may further explain the evolution and maintenance of these traits. C1 [Kim, Younghoon; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. EM emylonakis@partners.org FU National Institutes of Health [P01 AI083214, R01 AI075286, R21 AI079569] FX This study was supported by grants from the National Institutes of Health (P01 AI083214, R01 AI075286, and R21 AI079569) to E.M. NR 74 TC 15 Z9 20 U1 2 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD JUN PY 2011 VL 10 IS 6 BP 782 EP 790 DI 10.1128/EC.00014-11 PG 9 WC Microbiology; Mycology SC Microbiology; Mycology GA 770MP UT WOS:000291091100009 PM 21498643 ER PT J AU Chen, YL Brand, A Morrison, EL Silao, FGS Bigol, UG Malbas, FF Nett, JE Andes, DR Solis, NV Filler, SG Averette, A Heitman, J AF Chen, Ying-Lien Brand, Alexandra Morrison, Emma L. Silao, Fitz Gerald S. Bigol, Ursela G. Malbas, Fedelino F., Jr. Nett, Jeniel E. Andes, David R. Solis, Norma V. Filler, Scott G. Averette, Anna Heitman, Joseph TI Calcineurin Controls Drug Tolerance, Hyphal Growth, and Virulence in Candida dubliniensis SO EUKARYOTIC CELL LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CRYPTOCOCCUS-NEOFORMANS; ASPERGILLUS-FUMIGATUS; OROPHARYNGEAL CANDIDIASIS; ANTIFUNGAL SUSCEPTIBILITY; TRANSCRIPTION FACTOR; DENTURE STOMATITIS; INFECTED PATIENTS; CALCOFLUOR WHITE; GENE-EXPRESSION AB Candida dubliniensis is an emerging pathogenic yeast species closely related to Candida albicans and frequently found colonizing or infecting the oral cavities of HIV/AIDS patients. Drug resistance during C. dubliniensis infection is common and constitutes a significant therapeutic challenge. The calcineurin inhibitor FK506 exhibits synergistic fungicidal activity with azoles or echinocandins in the fungal pathogens C. albicans, Cryptococcus neoformans, and Aspergillus fumigatus. In this study, we show that calcineurin is required for cell wall integrity and wild-type tolerance of C. dubliniensis to azoles and echinocandins; hence, these drugs are candidates for combination therapy with calcineurin inhibitors. In contrast to C. albicans, in which the roles of calcineurin and Crz1 in hyphal growth are unclear, here we show that calcineurin and Crz1 play a clearly demonstrable role in hyphal growth in response to nutrient limitation in C. dubliniensis. We further demonstrate that thigmotropism is controlled by Crz1, but not calcineurin, in C. dubliniensis. Similar to C. albicans, C. dubliniensis calcineurin enhances survival in serum. C. dubliniensis calcineurin and crz1/crz1 mutants exhibit attenuated virulence in a murine systemic infection model, likely attributable to defects in cell wall integrity, hyphal growth, and serum survival. Furthermore, we show that C. dubliniensis calcineurin mutants are unable to establish murine ocular infection or form biofilms in a rat denture model. That calcineurin is required for drug tolerance and virulence makes fungus-specific calcineurin inhibitors attractive candidates for combination therapy with azoles or echinocandins against emerging C. dubliniensis infections. C1 [Chen, Ying-Lien; Averette, Anna; Heitman, Joseph] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Brand, Alexandra; Morrison, Emma L.] Univ Aberdeen, Inst Med Sci, Sch Med Sci, Aberdeen Fungal Grp, Aberdeen, Scotland. [Silao, Fitz Gerald S.] Dr Jose G Tamayo Med Univ, Univ Perpetual Help, Dept Microbiol & Parasitol, Binan, Laguna, Philippines. [Bigol, Ursela G.] Dept Sci & Technol, Environm & Biotechnol Div, Bicutan, Philippines. [Malbas, Fedelino F., Jr.] Res Inst Trop Med, Alabang, Philippines. [Nett, Jeniel E.; Andes, David R.] Univ Wisconsin, Dept Med, Madison, WI USA. [Nett, Jeniel E.; Andes, David R.] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. [Nett, Jeniel E.; Andes, David R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Solis, Norma V.; Filler, Scott G.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Filler, Scott G.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Heitman, J (reprint author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. EM heitm001@duke.edu OI Brand, Alexandra/0000-0002-7381-131X; Chen, Ying-Lien/0000-0002-1966-470X FU Duke University Center for AIDS Research (CFAR) [2P30 AI064518-06]; NIH [P30 AI64518, R01DE017088]; NIH/NIAID [AI42159, AI50438] FX This research was supported by the Duke University Center for AIDS Research (CFAR grant 2P30 AI064518-06 to Y.-L. Chen), NIH-funded program P30 AI64518 to Duke University, and NIH/NIAID R01 grants AI42159 and AI50438 (to J. Heitman). S. G. Filler and N. V. Solis were supported in part by NIH grant R01DE017088. NR 91 TC 41 Z9 43 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD JUN PY 2011 VL 10 IS 6 BP 803 EP 819 DI 10.1128/EC.00310-10 PG 17 WC Microbiology; Mycology SC Microbiology; Mycology GA 770MP UT WOS:000291091100011 PM 21531874 ER PT J AU Kang, ES Magkos, F Sienkiewicz, E Mantzoros, CS AF Kang, Eun Seok Magkos, Faidon Sienkiewicz, Elizabeth Mantzoros, Christos S. TI Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency or leptin administration in humans SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID SERINE-PROTEASE INHIBITOR; METHIONYL HUMAN LEPTIN; ADIPOSE-TISSUE; INSULIN-RESISTANCE; WEIGHT-LOSS; BARIATRIC SURGERY; SERUM VISFATIN; OBESE WOMEN; HEALTHY-MEN; IN-VIVO AB Objective: Animal and in vitro studies indicate that leptin alleviates starvation-induced reduction in circulating vaspin and stimulates the production of visfatin. We thus examined whether vaspin and visfatin are affected by short-and long-term energy deprivation and leptin administration in human subjects in vivo. Design and methods: We measured circulating levels of vaspin and visfatin i) before and after 72 h of starvation (leading to severe hypoleptinemia) with or without leptin administration in replacement doses in 13 normal-weight subjects, ii) before and after 72 h of starvation with leptin administration in pharmacological doses in 13 lean and obese subjects, iii) during chronic energy deficiency in eight women with hypothalamic amenorrhea on leptin replacement for 3 months, and iv) during chronic energy deficiency in 18 women with hypothalamic amenorrhea on leptin replacement or placebo for 3 months. Results: Acute starvation decreased serum leptin to 21% of baseline values, (P=0.002) but had no significant effect on vaspin and visfatin concentrations (P > 0.05). Nor did normalization of leptin levels affect the concentrations of these two adipokines (P > 0.9). Leptin replacement in women with hypothalamic amenorrhea did not significantly alter vaspin and visfatin concentrations, whether relative to baseline or placebo administration (P > 0.25). Pharmacological doses of leptin did not affect circulating vaspin and visfatin concentrations (P > 0.9). Conclusions: Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency leading to hypoleptinemia and are not regulated by leptin in human subjects, indicating that these adipocyte-secreted hormonal regulators of metabolism are independently regulated in humans. C1 [Kang, Eun Seok; Magkos, Faidon; Sienkiewicz, Elizabeth; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. [Kang, Eun Seok] Yonsei Univ, Coll Med, Dept Internal Med, Div Endocrinol & Metab,Severance Hosp Diabet Ctr, Seoul, South Korea. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Kang, ES (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Med, 330 Brookline Ave,SL Room 412, Boston, MA 02215 USA. EM ekang@bidmc.harvard.edu FU Harvard Clinical and Translational Science Center, from the National Center for Research Resources [UL1 RR025758, M01-RR-01032-]; National Institute of Diabetes and Digestive and Kidney Diseases [DK58785, DK79929, DK81913, AG032030]; Yonsei University College of Medicine [6-2011-0000]; Korean Government MEST [NRF-2010-013-E0008]; Beth Israel Deaconess Medical Center FX This work was supported by Grant Number UL1 RR025758 and M01-RR-01032- Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Funding was received from the National Institute of Diabetes and Digestive and Kidney Diseases grants DK58785, DK79929, and DK81913, AG032030; a faculty research grant from Yonsei University College of Medicine (6-2011-0000); and the National Research Foundation of Korea (Grant funded by the Korean Government MEST, Basic Research Promotion Fund, NRF-2010-013-E0008). The Mantzoros Laboratory is also supported by a discretionary grant from Beth Israel Deaconess Medical Center. Amgen, Inc., and Amylin Pharmaceuticals, Inc., supplied metreleptin for this study and approved the design of the study but had no role in the study design; conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 43 TC 11 Z9 14 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JUN PY 2011 VL 164 IS 6 BP 911 EP 917 DI 10.1530/EJE-11-0052 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 769MZ UT WOS:000291020500008 PM 21422197 ER PT J AU Desalermos, A Muhammed, M Glavis-Bloom, J Mylonakis, E AF Desalermos, Athanasios Muhammed, Maged Glavis-Bloom, Justin Mylonakis, Eleftherios TI Using Caenorhabditis elegans for antimicrobial drug discovery SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE Caenorhabditis elegans; Candida albicans; drug discovery; high throughput; model host ID THROUGHPUT SCREENING ASSAYS; HOST-PATHOGEN INTERACTIONS; ANIMAL INFECTION MODEL; CRYPTOCOCCUS-NEOFORMANS; C-ELEGANS; CANDIDA-ALBICANS; INNATE IMMUNITY; ACINETOBACTER-BAUMANNII; ANTIFUNGAL COMPOUNDS; ALZHEIMERS-DISEASE AB Introduction: The number of microorganism strains with resistance to known antimicrobials is increasing. Therefore, there is a high demand for new, nontoxic and efficient antimicrobial agents. Research with the microscopic nematode Caenorhabditis elegans can address this high demand for the discovery of new antimicrobial compounds. In particular, C. elegans can be used as a model host for in vivo drug discovery through high-throughput screens of chemical libraries. Areas covered: This review introduces the use of substitute model hosts and especially C. elegans in the study of microbial pathogenesis. The authors also highlight recently published literature on the role of C. elegans in drug discovery and outline its use as a promising host with unique advantages in the discovery of new antimicrobial drugs. Expert opinion: Caenorhabditis elegans can be used, as a model host, to research many diseases, including fungal infections and Alzheimer's disease. In addition, high-throughput techniques for screening chemical libraries can also be facilitated. Nevertheless, C. elegans and mammals have significant differences that both limit the use of the nematode in research and the degree by which results can be interpreted. That being said, the use of C. elegans in drug discovery still holds promise and the field continues to grow, with attempts to improve the methodology already underway. C1 [Desalermos, Athanasios; Muhammed, Maged; Glavis-Bloom, Justin; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St,Gray Jackson 5,Room GRJ 504, Boston, MA 02114 USA. EM emylonakis@partners.org FU NIH [P01 AI 083214, R01 AI075286, R21 AI079569]; Astellas Pharma, Inc. FX The authors work has been supported by NIH grants P01 AI 083214, R01 AI075286 and R21 AI079569. E Mylonakis has served on an Advisory Board and received research support from Astellas Pharma, Inc. The authors declare no other conflict of interest. NR 93 TC 12 Z9 13 U1 3 U2 19 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1746-0441 EI 1746-045X J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD JUN PY 2011 VL 6 IS 6 BP 645 EP 652 DI 10.1517/17460441.2011.573781 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768VJ UT WOS:000290966200005 PM 21686092 ER PT J AU Hofstatter, EW Domchek, SM Miron, A Garber, J Wang, M Componeschi, K Boghossian, L Miron, PL Nathanson, KL Tung, N AF Hofstatter, Erin W. Domchek, Susan M. Miron, Alexander Garber, Judy Wang, Molin Componeschi, Kathryn Boghossian, Leigh Miron, Penelope L. Nathanson, Katherine L. Tung, Nadine TI PALB2 mutations in familial breast and pancreatic cancer SO FAMILIAL CANCER LA English DT Article DE BRCA2; Breast cancer; PALB2; Pancreatic cancer ID BRCA2-INTERACTING PROTEIN; SUSCEPTIBILITY GENE; FANCONI-ANEMIA; BRCA2; ELECTROPHORESIS AB PALB2 (Partner And Localizer of BRCA2) binds to and co-localizes with BRCA2 in DNA repair. Germline mutations in PALB2 have been identified in approximately 1-2% of familial breast cancer and 3-4% of familial pancreatic cancer cases. The goal of this study was to evaluate the prevalence of PALB2 mutations in women with breast cancer without BRCA1/2 mutations who also had a personal or family history of pancreatic cancer. PALB2 mutation analysis was performed in 94 non-BRCA1/2 breast cancer patients with a personal or family history of pancreatic cancer. Two truncating PALB2 mutations, c.3549C > CA and c.2962C > CT, were identified resulting in a mutation prevalence of 2.1%. The proband found to carry the c.3549C > CA PALB2 mutation had a mother diagnosed with both breast and pancreatic cancer; this relative was subsequently confirmed to carry the identical mutation. The proband with the c.2962C > CT mutation had a father and paternal aunt diagnosed with pancreatic cancer; neither relative was available for testing. Two novel PALB2 missense variants were also found, one of which was deemed potentially deleterious. The prevalence rate of PALB2 mutations in a non-BRCA1/2 breast cancer population specifically selected for a family history of pancreatic cancer does not appear to be significantly increased compared to that observed in other breast cancer populations studied thus far. Further evaluation is needed to determine the prevalence of PALB2 mutations and the clinical utility of such testing in those individuals affected with both breast and pancreatic cancers. C1 [Hofstatter, Erin W.] Yale Univ, Sch Med, Yale Canc Ctr, Sect Med Oncol, New Haven, CT 06520 USA. [Domchek, Susan M.; Boghossian, Leigh; Nathanson, Katherine L.] Univ Penn, Div Med Oncol, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Miron, Alexander; Miron, Penelope L.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Wang, Molin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Componeschi, Kathryn; Tung, Nadine] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. RP Hofstatter, EW (reprint author), Yale Univ, Sch Med, Yale Canc Ctr, Sect Med Oncol, 333 Cedar St,POB 208032, New Haven, CT 06520 USA. EM erin.hofstatter@yale.edu OI Nathanson, Katherine/0000-0002-6740-0901 FU Breast Cancer Research Foundation; Dana Farber/Harvard Cancer Center [CA 006516]; Dana Farber/Harvard Cancer Center Breast SPORE [CA 089393]; Mac-Donald Family Foundation FX This work was supported by grants from the Breast Cancer Research Foundation (to KLN, NT, and JG); the Dana Farber/Harvard Cancer Center (CA 006516); the Dana Farber/Harvard Cancer Center Breast SPORE (CA 089393); and the Mac-Donald Family Foundation (to SMD). NR 27 TC 36 Z9 36 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9600 J9 FAM CANCER JI Fam. Cancer PD JUN PY 2011 VL 10 IS 2 BP 225 EP 231 DI 10.1007/s10689-011-9426-1 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 768LZ UT WOS:000290937500007 PM 21365267 ER PT J AU Inman, AG Altman, A Kaduvettoor-Davidson, A Carr, A Walker, JA AF Inman, Arpana G. Altman, Abby Kaduvettoor-Davidson, Anju Carr, Amanda Walker, Jessica A. TI Cultural Intersections: A Qualitative Inquiry into the Experience of Asian Indian-White Interracial Couples SO FAMILY PROCESS LA English DT Article DE Asian Indian-White Couples; Interracial Marriages; Qualitative Study ID COUNSELING PSYCHOLOGY; CONFLICT; THERAPY AB The purpose of this study was to examine the "lived experience" of Asian Indian (AI)-White couples in interracial marriages. Ten highly educated AI-White professional couples were individually interviewed about their subjective experience of being in an interracial marriage, the challenges and strengths of this marriage, and the potential role of culture in their marriages. Data were analyzed using the Consensual Qualitative Research methodology. Results indicated that the couples' marital experiences were influenced by a complex intersection of ecosystemic factors with significant psychological impacts. These findings highlight shortcomings in drawing simplistic conclusions regarding the success or failure of an interracial marriage and have important implications for theory, research, and clinical practice. C1 [Inman, Arpana G.; Carr, Amanda] Lehigh Univ, Bethlehem, PA 18015 USA. [Altman, Abby] VA Boston Healthcare Syst, Boston, MA USA. [Kaduvettoor-Davidson, Anju] Univ Delaware, Ctr Counseling & Student Dev, Newark, DE 19716 USA. [Walker, Jessica A.] WG Bill Hefner VA Med Ctr, Salisbury, NC USA. RP Inman, AG (reprint author), Lehigh Univ, 111 Res Dr, Bethlehem, PA 18015 USA. EM agi2@lehigh.edu NR 47 TC 4 Z9 4 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-7370 J9 FAM PROCESS JI Fam. Process PD JUN PY 2011 VL 50 IS 2 BP 248 EP 266 DI 10.1111/j.1545-5300.2011.01358.x PG 19 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 763FP UT WOS:000290541000009 PM 21564064 ER PT J AU Crawford, JM Hoffman, RD Black-Schaffer, WS AF Crawford, James M. Hoffman, Robert D. Black-Schaffer, W. Stephen TI Pathology subspecialty fellowship application reform 2007 to 2010 SO HUMAN PATHOLOGY LA English DT Article DE Subspecialty fellowship; Pathology; Anatomic pathology; Clinical pathology; Exploding market; NRMP; Match ID GASTROENTEROLOGY MATCH; RADIOLOGY FELLOWSHIP; SUCCEED; MARKET AB The specialty of Pathology and Laboratory Medicine has entered into a phase when the 4-year sequence of Anatomic Pathology and/or Clinical Pathology Residency Training is almost universally followed by 1 or more years of Subspecialty Fellowship Training. Such training may occur in one of the American Board of Pathology-recognized subspecialties or any number of "subspecialty fellowships" that, although not leading to subspecialty board certification, may nevertheless fall under the oversight of the local institutional Graduate Medical Education Committee and the Accreditation Council for Graduate Medical Education Review Committee for Pathology. Unlike the application process for first-year Pathology Residency, which is run through the National Resident Matching Program, applications for Subspecialty Pathology Fellowships are not coordinated by any consistent schedule. Competition for Subspecialty Pathology Fellowships has consistently resulted in undesirable drift of the fellowship application process to dates that are unacceptably early for many fellowship applicants. Responding to widespread dissatisfaction voiced by national pathology resident organizations, in 2007, the Association of Pathology Chairs began evaluation and potential intervention in the fellowship application process. Three years of intermittently intense discussion, surveys, and market analysis, have led the Council of the Association of Pathology Chairs to recommend implementation of a Pathology Subspecialty Fellowship Matching program starting in the 2011 to 2012 recruiting year, for those Applicants matriculating in fellowship programs July 2013. We report on the data that informed this decision and discuss the pros and cons that are so keenly felt by the stakeholders in this as-yet-incomplete reform process. (C) 2011 Elsevier Inc. All rights reserved. C1 [Crawford, James M.] N Shore Long Isl Jewish Hlth Syst, Dept Pathol & Lab Med, Manhasset, NY 11042 USA. [Crawford, James M.] Hofstra N Shore LIJ Sch Med, Manhasset, NY 11042 USA. [Hoffman, Robert D.] Vanderbilt Univ, Dept Pathol, Sch Med, Nashville, TN 37232 USA. [Black-Schaffer, W. Stephen] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Black-Schaffer, W. Stephen] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Crawford, JM (reprint author), N Shore LIJ Labs, Lake Success, NY 11042 USA. EM jcrawford1@nshs.edu NR 30 TC 3 Z9 3 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUN PY 2011 VL 42 IS 6 SI SI BP 774 EP 794 DI 10.1016/j.humpath.2010.08.002 PG 21 WC Pathology SC Pathology GA 770GY UT WOS:000291076200004 PM 21035167 ER PT J AU Weingart, SN Zhu, JY Chiappetta, L Stuver, SO Schneider, EC Epstein, AM David-Kasdan, JA Annas, CL Fowler, FJ Weissman, JS AF Weingart, Saul N. Zhu, Junya Chiappetta, Laurel Stuver, Sherri O. Schneider, Eric C. Epstein, Arnold M. David-Kasdan, Jo Ann Annas, Catherine L. Fowler, Floyd J., Jr. Weissman, Joel S. TI Hospitalized patients' participation and its impact on quality of care and patient safety SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE medical error; adverse events; patient participation ID ADVERSE DRUG EVENTS; PATIENTS TELL US; HEALTH-CARE; MEDICAL ERRORS; INVOLVEMENT; INTERNET; INTERVENTION; EXPERIENCE; DISCHARGE; SYMPTOMS AB To understand the extent to which hospitalized patients participate in their care, and the association of patient participation with quality of care and patient safety. Random sample telephone survey and medical record review. US acute care hospitals in 2003. A total of 2025 recently hospitalized adults. Hospitalized patients reported participation in their own care, assessments of overall quality of care and the presence of adverse events (AEs) in telephone interviews. Physician reviewers rated the severity and preventability of AEs identified by interview and chart review among 788 surveyed patients who also consented to medical record review. Of the 2025 patients surveyed, 99.9 of patients reported positive responses to at least one of seven measures of participation. High participation (use of 4 activities) was strongly associated with patients' favorable ratings of the hospital quality of care (adjusted OR: 5.46, 95 CI: 4.157.19). Among the 788 patients with both patient survey and chart review data, there was an inverse relationship between participation and adverse events. In multivariable logistic regression analyses, patients with high participation were half as likely to have at least one adverse event during the admission (adjusted OR 0.49, 0.310.78). Most hospitalized patients participated in some aspects of their care. Participation was strongly associated with favorable judgments about hospital quality and reduced the risk of experiencing an adverse event. C1 [Weingart, Saul N.; Zhu, Junya; Chiappetta, Laurel; Stuver, Sherri O.] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. [Zhu, Junya] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. [Schneider, Eric C.; Epstein, Arnold M.; Weissman, Joel S.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Schneider, Eric C.; Epstein, Arnold M.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [David-Kasdan, Jo Ann; Weissman, Joel S.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Annas, Catherine L.] Eastern Massachusetts Healthcare Initiat, Cambridge, MA USA. [Fowler, Floyd J., Jr.] Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. [Weissman, Joel S.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Weissman, Joel S.] Commonwealth Massachusetts, Execut Off Hlth & Human Serv, Boston, MA USA. RP Weingart, SN (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 44 Binney St, Boston, MA 02115 USA. EM saul_weingart@dfci.harvard.edu OI Stuver, Sherri/0000-0002-4027-2663; Schneider, Eric/0000-0002-1132-5084 FU US Agency for Healthcare Research and Quality [U18 HS11928]; Center for Patient Safety, Dana-Farber Cancer Institute FX This work was supported by a Cooperative Agreement from the US Agency for Healthcare Research and Quality to the Massachusetts Department of Public Health [U18 HS11928]; and the Center for Patient Safety, Dana-Farber Cancer Institute. NR 42 TC 36 Z9 40 U1 3 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD JUN PY 2011 VL 23 IS 3 BP 269 EP 277 DI 10.1093/intqhc/mzr002 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 763VI UT WOS:000290587400008 PM 21307118 ER PT J AU Pessach, IM Ordovas-Montanes, J Zhang, SY Casanova, JL Giliani, S Gennery, AR Al-Herz, W Manos, PD Schlaeger, TM Park, IH Rucci, F Agarwal, S Mostoslavsky, G Daley, GQ Notarangelo, LD AF Pessach, Itai M. Ordovas-Montanes, Jose Zhang, Shen-Ying Casanova, Jean-Laurent Giliani, Silvia Gennery, Andrew R. Al-Herz, Waleed Manos, Philip D. Schlaeger, Thorsten M. Park, In-Hyun Rucci, Francesca Agarwal, Suneet Mostoslavsky, Gustavo Daley, George Q. Notarangelo, Luigi D. TI Induced pluripotent stem cells: A novel frontier in the study of human primary immunodeficiencies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Primary immunodeficiency; induced pluripotent stem cells; reprogramming ID HERPES-SIMPLEX ENCEPHALITIS; HYPER-IGE SYNDROME; IPS CELLS; EFFICIENT GENERATION; DOPAMINERGIC-NEURONS; IN-VITRO; HUMAN ES; DIFFERENTIATION; DEFICIENCY; DERIVATION AB Background: The novel ability to epigenetically reprogram somatic cells into induced pluripotent stem cells (iPSCs) through the exogenous expression of transcription promises to revolutionize the study of human diseases. Objective: Here we report on the generation of 25 iPSC lines from 6 patients with various forms of primary immunodeficiencies (PIDs) affecting adaptive immunity, innate immunity, or both. Methods: Patients' dermal fibroblasts were reprogrammed by expression of 4 transcription factors, octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), Krueppel-like factor 4 (KLF4), and cellular myelomonocytosis proto-oncogene (cMYC), by using a single excisable polycistronic lentiviral vector. Results: iPSCs derived from patients with PIDs show a stemness profile that is comparable with that observed in human embryonic stem cells. After in vitro differentiation into embryoid bodies, pluripotency of the patient-derived iPSC lines was demonstrated by expression of genes characteristic of each of the 3 embryonic layers. We have confirmed the patient-specific origin of the iPSC lines and ascertained maintenance of karyotypic integrity. Conclusion: By providing a limitless source of diseased stem cells that can be differentiated into various cell types in vitro, the repository of iPSC lines from patients with PIDs represents a unique resource to investigate the pathophysiology of hematopoietic and extrahematopoietic manifestations of these diseases and might assist in the development of novel therapeutic approaches based on gene correction. (J Allergy Clin Immunol 2011;127:1400-7.) C1 [Pessach, Itai M.; Ordovas-Montanes, Jose; Rucci, Francesca; Notarangelo, Luigi D.] Harvard Univ, Sch Med, Div Immunol, Childrens Hosp Boston, Boston, MA 02115 USA. [Pessach, Itai M.] Safra Childrens Hosp, Talpiot Med Leadership Program, Sheba Med Ctr, Tel Hashomer, Israel. [Ordovas-Montanes, Jose] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Zhang, Shen-Ying; Casanova, Jean-Laurent] Rockefeller Univ, St Giles Lab Human Genet Infect Dis, Rockefeller Branch, New York, NY 10021 USA. [Casanova, Jean-Laurent] Univ Paris 05, Lab Human Genet Infect Dis, Necker Branch, Paris, France. [Casanova, Jean-Laurent] Necker Med Sch, INSERM U980, Paris, France. [Giliani, Silvia] Univ Brescia, Dept Pediat, Angelo Nocivelli Inst Mol Med, Brescia, Italy. [Gennery, Andrew R.] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England. [Al-Herz, Waleed] Al Sabah Hosp, Dept Pediat, Allergy & Clin Immunol Unit, Kuwait, Kuwait. [Manos, Philip D.; Schlaeger, Thorsten M.; Park, In-Hyun; Agarwal, Suneet; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA USA. [Manos, Philip D.; Schlaeger, Thorsten M.; Park, In-Hyun; Agarwal, Suneet; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Manos, Philip D.; Schlaeger, Thorsten M.; Park, In-Hyun; Daley, George Q.] Childrens Hosp Boston, Stem Cell Program, Boston, MA USA. [Schlaeger, Thorsten M.; Agarwal, Suneet; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, England. [Park, In-Hyun] Yale Univ, Sch Med, Yale Stem Cell Ctr, Dept Genet, New Haven, CT 06520 USA. [Agarwal, Suneet; Daley, George Q.; Notarangelo, Luigi D.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Mostoslavsky, Gustavo] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Mostoslavsky, Gustavo] Boston Univ, Sch Med, Ctr Regenerat Med CReM, Boston, MA 02118 USA. RP Notarangelo, LD (reprint author), Harvard Univ, Sch Med, Div Immunol, Childrens Hosp Boston, Karp Bldg,Rm 9210,1 Blackfan Circle, Boston, MA 02115 USA. EM luigi.notarangelo@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 FU National Institutes of Health [1R03AI088352-01, 1R21AI0898-10-01]; March of Dimes [6-FY10-282]; Translation Research Program; Harvard Catalyst Grant; Manton Foundation; Fondazione "Angelo Nocivelli" FX Supported by National Institutes of Health grants 1R03AI088352-01 and 1R21AI0898-10-01, March of Dimes grant 6-FY10-282, the Translation Research Program (all to L.D.N.), and a Harvard Catalyst Grant (to G.Q.D.). Also supported by the Manton Foundation (to L.D.N. and G.Q.D.) and by Fondazione "Angelo Nocivelli" (to S.G.). NR 61 TC 28 Z9 28 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2011 VL 127 IS 6 BP 1400 EP U140 DI 10.1016/j.jaci.2010.11.008 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA 769WH UT WOS:000291048500011 PM 21185069 ER PT J AU Biagtan, MJ Viswanathan, RK Evans, MD Mathur, SK AF Biagtan, Mark J. Viswanathan, Ravi K. Evans, Michael D. Mathur, Sameer K. TI Clinical utility of the Chronic Urticaria Index SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID CHRONIC IDIOPATHIC URTICARIA; CHRONIC AUTOIMMUNE URTICARIA C1 [Biagtan, Mark J.; Viswanathan, Ravi K.; Mathur, Sameer K.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Viswanathan, Ravi K.; Mathur, Sameer K.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Evans, Michael D.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. RP Biagtan, MJ (reprint author), Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM sm4@medicine.wisc.edu OI Evans, Michael/0000-0001-7449-3993 FU NIAID NIH HHS [T32 AI007635, AI007635, T32 AI007635-12] NR 10 TC 9 Z9 9 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2011 VL 127 IS 6 BP 1626 EP 1627 DI 10.1016/j.jaci.2011.01.045 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 769WH UT WOS:000291048500047 PM 21376378 ER PT J AU Waldman, AT Gorman, MP Rensel, MR Austin, TE Hertz, DP Kuntz, NL AF Waldman, Amy T. Gorman, Mark P. Rensel, Mary R. Austin, Tracy E. Hertz, Deborah P. Kuntz, Nancy L. CA Network Pediat Multiple Sclerosis TI Management of Pediatric Central Nervous System Demyelinating Disorders: Consensus of United States Neurologists SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE multiple sclerosis; acute disseminated encephalomyelitis; optic neuritis ID ACUTE DISSEMINATED ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; OPTIC NEURITIS; CHILDREN AB Demyelinating diseases are a group of autoimmune inflammatory disorders affecting the central nervous system in adults and children; however, the diagnosis, evaluation, and treatment of these disorders are primarily based on adult data. The purpose of this study was to assess the practice patterns of US physicians who specialize in treating acquired central nervous system demyelinating diseases in children and adolescents. The Delphi technique was used to identify areas of consensus in management and treatment. Forty-two experts in the field participated in the process. Intravenous methylprednisolone was the first-line treatment of choice for acute episodes of all forms of demyelinating disease; however, consensus was lacking regarding specific dose, treatment duration, and use of an oral taper. First-line disease-modifying therapies for pediatric multiple sclerosis were interferons and glatiramer acetate, chosen based on perceived efficacy and tolerability, respectively. Areas lacking agreement among the expert panel and requiring further research are identified. C1 [Kuntz, Nancy L.] Childrens Mem Hosp, Dept Pediat, Chicago, IL 60614 USA. [Waldman, Amy T.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Waldman, Amy T.] Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA. [Waldman, Amy T.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Gorman, Mark P.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Gorman, Mark P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rensel, Mary R.] Cleveland Clin, Dept Neurol, Cleveland, OH 44106 USA. [Austin, Tracy E.; Hertz, Deborah P.] Natl Multiple Sclerosis Soc, New York, NY USA. RP Kuntz, NL (reprint author), Childrens Mem Hosp, Dept Pediat, 2300 Childrens Plaza,Box 51, Chicago, IL 60614 USA. EM nkuntz@childrensmemorial.org FU NINDS NIH HHS [K08 NS060695] NR 14 TC 32 Z9 37 U1 0 U2 1 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 JUN PY 2011 VL 26 IS 6 BP 675 EP 682 DI 10.1177/0883073810395141 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 768TJ UT WOS:000290961000002 PM 21518802 ER PT J AU Nahed, BV Ferreira, M Babu, MA Terry, AR Walcott, BP Kahle, KT Smith, ER AF Nahed, Brian V. Ferreira, Manuel, Jr. Babu, Maya A. Terry, Anna R. Walcott, Brian P. Kahle, Kristopher T. Smith, Edward R. TI Dural Scalp and Intracranial Hemangiomas Causing Hydrocephalus and Venous Sinus Thrombosis in an Infant SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE hemangioma; hydrocephalus; thrombosis; venous; dural ID CEREBRAL SINOVENOUS THROMBOSIS; ARTERIAL ISCHEMIC-STROKE; IRON-DEFICIENCY ANEMIA; CAPILLARY HEMANGIOMA; CHILDREN; HOMOCYSTINURIA; PROPRANOLOL; CAVERNOMAS; DISORDERS; NEONATE AB Cutaneous scalp hemangiomas may herald the presence of occult intracranial hemangiomas. A previously healthy 4-month-old girl presented with a bleeding scalp hemangioma, a bulging fontanel, and anemia. Magnetic resonance imaging (MRI) of the brain revealed hydrocephalus along with multiple intracranial hemangiomas. These lesions compressed the jugular foramina, resulting in venous sinus thrombosis involving the right transverse sinus, the left sigmoid sinus, and the torcular herophili. The patient had no family history of phakomatoses or other genetic abnormalities. A thrombophilia work-up result was unremarkable. The patient was treated with prednisolone (10 mg twice daily) and low molecular weight heparin (1 mg/kg/dose) twice daily. This treatment decreased the size of her cutaneous and intracranial hemangiomas and led to the resolution of her venous sinus thromboses and hydrocephalus. Innocuous scalp hemangioma in an infant may herald more concerning intracranial pathology, which can be treated effectively if diagnosed with appropriate imaging studies. C1 [Smith, Edward R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurosurg, Boston, MA 02115 USA. [Nahed, Brian V.; Ferreira, Manuel, Jr.; Babu, Maya A.; Terry, Anna R.; Walcott, Brian P.; Kahle, Kristopher T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Smith, ER (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurosurg, 300 Longwood Ave, Boston, MA 02115 USA. EM Edward.smith@childrens.harvard.edu NR 39 TC 2 Z9 2 U1 0 U2 2 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 JUN PY 2011 VL 26 IS 6 BP 777 EP 781 DI 10.1177/0883073810390694 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 768TJ UT WOS:000290961000019 PM 21325128 ER PT J AU Molitch, ME Clemmons, DR Malozowski, S Merriam, GR Vance, ML AF Molitch, Mark E. Clemmons, David R. Malozowski, Saul Merriam, George R. Vance, Mary Lee TI Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GH-REPLACEMENT THERAPY; BONE-MINERAL DENSITY; QUALITY-OF-LIFE; INTIMA-MEDIA THICKNESS; TRAUMATIC BRAIN-INJURY; CARDIOVASCULAR RISK-FACTORS; BASE-LINE CHARACTERISTICS; RECOMBINANT HUMAN GH; BODY-MASS INDEX; BENIGN INTRACRANIAL HYPERTENSION AB Objective: The aim was to update The Endocrine Society Clinical Practice Guideline on Evaluation and Treatment of Adult Growth Hormone Deficiency (GHD) previously published in 2006. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions through a series of conference calls and e-mails. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. Conclusions: GHD can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. GH therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks associated with GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual. (J Clin Endocrinol Metab 96: 1587-1609, 2011) C1 [Molitch, Mark E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Clemmons, David R.] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. [Malozowski, Saul] Natl Inst Diabet Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA. [Merriam, George R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98493 USA. [Merriam, George R.] Univ Washington, Sch Med, Tacoma, WA USA. [Vance, Mary Lee] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22908 USA. RP Molitch, ME (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. EM govt-prof@endo-society.org FU Eli Lilly, Co.; American Diabetes Association; American College of Physicians; Pituitary Society; Sanofi Aventis; Ipsen; Corcept; Pfizer, Inc.; Genentech, Inc.; Lilly Inc.; Ipsen Inc.; America Neuroendocrine Society; National Institutes of Health; Washington State Health Department; Novo Nordisk, Inc.; Novartis Pharmaceuticals FX Financial Disclosures of the Task Force: Mark E. Molitch, M. D. (chair)-Financial or Business/Organizational Interests: Eli Lilly, Co., American Diabetes Association, American College of Physicians, Pituitary Society, Sanofi Aventis, Ipsen, Corcept; Significant Financial Interest or Leadership Position: none declared. David R. Clemmons, M. D.-Financial or Business/Organizational Interests: Pfizer, Inc., Genentech, Inc., Lilly Inc., Ipsen Inc.; Significant Financial Interest or Leadership Position: none declared. Saul Malozowski, M. D.-Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: none declared. George R. Merriam, M. D.-Financial or Business/Organizational Interests: America Neuroendocrine Society, National Institutes of Health, Washington State Health Department; Significant Financial Interest or Leadership Position: Novo Nordisk, Inc., Eli Lilly, Co., American Neuroendocrine Society. Mary Lee Vance, M. D.-Financial or Business/Organizational Interests: Novartis Pharmaceuticals, Ipsen; Significant Financial Interest or Leadership Position: none declared. NR 215 TC 198 Z9 211 U1 1 U2 15 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2011 VL 96 IS 6 BP 1587 EP 1609 DI 10.1210/jc.2011-0179 PG 23 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 766TU UT WOS:000290810200029 PM 21602453 ER PT J AU Eckel, RH Kahn, SE Ferrannini, E Goldfine, AB Nathan, DM Schwartz, MW Smith, RJ Smith, SR AF Eckel, Robert H. Kahn, Steven E. Ferrannini, Ele Goldfine, Allison B. Nathan, David M. Schwartz, Michael W. Smith, Robert J. Smith, Steven R. TI Obesity and Type 2 Diabetes: What Can Be Unified and What Needs to Be Individualized? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; GENOME-WIDE ASSOCIATION; LIFE-STYLE INTERVENTION; Y GASTRIC BYPASS; BARIATRIC SURGERY; ADIPOSE-TISSUE; GLYCEMIC INDEX; WEIGHT-LOSS; MELLITUS; IDENTIFICATION AB Objective: This report examines what is known about the relationship between obesity and type 2 diabetes and how future research in these areas might be directed to benefit prevention, interventions, and overall patient care. Research Design and Methods: An international working group of 32 experts in the pathophysiology, genetics, clinical trials, and clinical care of obesity and/or type 2 diabetes participated in a conference held on 6-7 January 2011 and cosponsored by The Endocrine Society, the American Diabetes Association, and the European Association for the Study of Diabetes. A writing group comprising eight participants subsequently prepared this summary and recommendations. Participants reviewed and discussed published literature and their own unpublished data. Results: The writing group unanimously supported the summary and recommendations as representing the working group's majority or unanimous opinions. Conclusions: The major questions linking obesity to type 2 diabetes that need to be addressed by combined basic, clinical, and population-based scientific approaches include the following: 1) Why do not all patients with obesity develop type 2 diabetes? 2) Through what mechanisms do obesity and insulin resistance contribute to beta-cell decompensation, and if/when obesity prevention ensues, how much reduction in type 2 diabetes incidence will follow? 3) How does the duration of type 2 diabetes relate to the benefits of weight reduction by lifestyle, weight-loss drugs, and/or bariatric surgery on beta-cell function and glycemia? 4) What is necessary for regulatory approval of medications and possibly surgical approaches for preventing type 2 diabetes in patients with obesity? Improved understanding of how obesity relates to type 2 diabetes may help advance effective and cost-effective interventions for both conditions, including more tailored therapy. To expedite this process, we recommend further investigation into the pathogenesis of these coexistent conditions and innovative approaches to their pharmacological and surgical management. ( J Clin Endocrinol Metab 96: 1654-1663, 2011) C1 [Eckel, Robert H.] Univ Colorado, Div Endocrinol Metab & Diabet, Dept Med, Aurora, CO 80045 USA. Univ Washington, Seattle, WA 98108 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Ferrannini, Ele] Univ Pisa, Dept Internal Med, I-56100 Pisa, Italy. [Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Goldfine, Allison B.] Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. [Nathan, David M.] Massachusetts Gen Hosp, Clin Res Ctr, Boston, MA 02114 USA. [Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Schwartz, Michael W.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98109 USA. [Smith, Robert J.] Brown Univ, Alpert Med Sch, Div Endocrinol, Providence, RI 02914 USA. [Smith, Robert J.] Brown Univ, Alpert Med Sch, Hallett Ctr Diabet & Endocrinol, Providence, RI 02914 USA. [Smith, Steven R.] Florida Hosp Sanford, Burnham Res Inst, Orlando, FL 32827 USA. RP Eckel, RH (reprint author), Univ Colorado, Div Endocrinol Metab & Diabet, Dept Med, Anschutz Med Campus,12801 E 17th Ave,Box 8106,RC-, Aurora, CO 80045 USA. EM robert.eckel@ucdenver.edu; skahn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU Endocrine Society; American Diabetes Association; European Association for the Study of Diabetes; Novo Nordisk; Sanofi Research Grant; dia-Dexus; GlaxoSmithKline; Cardiometabolic Health Congress and Metabolic Syndrome Institute; Eli Lilly; Intarcia Therapeutics; Boehringer Ingelheim; Merck; Daiichi Sankyo; Bristol-Myers Squibb/AstraZeneca; sanofi-aventis; Novartis; Pfizer; Orexigen; GI Dynamics; Amylin FX This article is based on a conference jointly sponsored by The Endocrine Society, the American Diabetes Association, and the European Association for the Study of Diabetes, with the financial support of an unrestricted educational grant from Novo Nordisk.; R.H.E. received grant/research support from Sanofi Research Grant (fellowship educational grant), dia-Dexus, and GlaxoSmithKline; compensation for working as a consultant for Amylin, GTC Nutrition, Genfit, Eli Lilly, Pfizer, Johnson&Johnson, and Esperion; financial or material support from Cardiometabolic Health Congress and Metabolic Syndrome Institute; and honoraria from Vindico, CME Incite, and Voxmedia. S. E. K. received consulting fees from Eli Lilly, GlaxoSmithKline, Intarcia Therapeutics, and Novo Nordisk for acting as an advisory board member; consulting fees and honoraria from Boehringer Ingelheim and Merck for acting as an advisory board member and speaker; and grant support from Daiichi Sankyo. E. F. received consulting fees from Merck, Boehringer Ingelheim, Bristol-Myers Squibb/AstraZeneca, sanofi-aventis, Novartis, GlaxoSmithKline, and Daiichi Sankyo and grant support from Merck and Eli Lilly. A. B. G. acted as Site Principal Investigator for a clinical trial funded by Eli Lilly that is now complete with results published. M. W. S. received consulting fees from Merck, Pfizer, and Orexigen. R.J.S. received consulting fees from GI Dynamics and royalties from Baxter and Fresenius Kabi. S. R. S. received consulting fees from Amylin, Bristol-Myers Squibb, Eli Lilly, and Novartis and consulting fees as an advisory board member for Arena. No other potential conflicts of interest relevant to this article were reported. NR 50 TC 69 Z9 70 U1 1 U2 10 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2011 VL 96 IS 6 BP 1654 EP 1663 DI 10.1210/jc.2011-0585 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 766TU UT WOS:000290810200036 PM 21602457 ER PT J AU Biller, BMK Ji, HJ Ahn, H Savoy, C Siepl, EC Popovic, V Coculescu, M Roemmler, J Gavrila, C Cook, DM Strasburger, CJ AF Biller, Beverly M. K. Ji, Hyi-Jeong Ahn, Hyunji Savoy, Conrad Siepl, E. Christine Popovic, Vera Coculescu, Mihail Roemmler, Josefine Gavrila, Catalin Cook, David M. Strasburger, Christian J. TI Effects of Once-Weekly Sustained-Release Growth Hormone: A Double-Blind, Placebo-Controlled Study in Adult Growth Hormone Deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GH DEFICIENCY; HYPOPITUITARY ADULTS; DOSE TITRATION; SACCHAROMYCES-CEREVISIAE; REPLACEMENT; EFFICACY; ANTIBODIES; CHILDREN; THERAPY; LB03002 AB Background: A sustained-release recombinant human GH formulation, LB03002, has been recently developed, with pharmacokinetics and pharmacodynamic activity appropriate for once-weekly administration. LB03002 is a long-acting GH that is administered once a week by sc injection. Objective: This study evaluated efficacy and safety of LB03002 in adult patients with GH deficiency. Patients and Methods: A total of 152 patients were randomized to receive LB03002 or placebo once weekly for 26 wk. Changes in body composition were evaluated from DXA (dual-energy x-ray absorptiometry). IGF-I was assessed at each study visit. Safety was assessed from adverse events, glucose homeostasis, and antibody development. Results: IGF-I increased significantly (P < 0.001) with LB03002 and remained unchanged with placebo. Mean fat mass (FM) decreased by 1.052 kg [95% confidence interval (CI) = -1.614 to -0.491] in the LB03002 group vs. an increase of 0.570 kg (95% CI = -0.205-1.345) in the placebo group; treatment difference was 1.622 kg (95% CI = -2.527 to -0.717; P < 0.001). FM change was mainly due to decreased trunk fat. Least square mean treatment difference was 1.032 kg (95% CI = -1.560 to -0.515; P < 0.001). LBM (lean body mass) was significantly increased with LB03002 vs. placebo (least square mean difference was 1.393 kg; 95% CI = 0.614-2.171; P < 0.001). No concerning safety issues arose during the study. Conclusions: Weekly GH replacement with the sustained-release preparation LB03002 in adults significantly reduced FM over 6 months and was well tolerated. (J Clin Endocrinol Metab 96: 1718-1726, 2011) C1 [Biller, Beverly M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ji, Hyi-Jeong; Ahn, Hyunji] LG Life Sci Ltd, Seoul 150721, South Korea. [Savoy, Conrad; Siepl, E. Christine] Biopartners GmbH, CH-6340 Baar, Switzerland. [Popovic, Vera] Inst Endocrinol, Belgrade 11000, Serbia. [Coculescu, Mihail] CI Parhon, Inst Endocrinol, Bucharest 011863, Romania. [Roemmler, Josefine] Univ Munich, D-80336 Munich, Germany. [Gavrila, Catalin] SANA Med Ctr, Bucharest 011025, Romania. [Cook, David M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Strasburger, Christian J.] Campus Charite, Dept Med, Div Clin Endocrinol, D-10117 Berlin, Germany. RP Biller, BMK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM bbiller@partners.org RI Coculescu, Mihail/D-7162-2011 OI Coculescu, Mihail/0000-0003-1468-9446 FU LG Life Sciences, Ltd., Korea; Biopartners, GmbH, Switzerland FX H.J.J. and H. A. are employees of LG Life Sciences, Ltd.; C. S. and E. C. S. are employees of Biopartners, GmbH. B. M. K. B. and C.J.S. received consulting fees from LG Life Sciences, Ltd., Korea, and Biopartners, GmbH, Switzerland. V. P., M. C., J.R., C. G., and D. M. C. have nothing to declare. NR 21 TC 26 Z9 26 U1 0 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2011 VL 96 IS 6 BP 1718 EP 1726 DI 10.1210/jc.2010-2819 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 766TU UT WOS:000290810200046 PM 21411551 ER PT J AU Chan, YM Butler, JP Pinnell, NE Pralong, FP Crowley, WF Ren, C Chan, KK Seminara, SB AF Chan, Yee-Ming Butler, James P. Pinnell, Nancy E. Pralong, Francois P. Crowley, William F., Jr. Ren, Chen Chan, Kenneth K. Seminara, Stephanie B. TI Kisspeptin Resets the Hypothalamic GnRH Clock in Men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; HYPOGONADOTROPIC HYPOGONADISM; NEUROENDOCRINE CONTROL; OLFACTORY PLACODE; RECEPTOR GPR54; IN-VIVO; SECRETION; NEURONS; PUBERTY; INCREASE AB Context: Reproduction in all mammals is controlled by a hypothalamic clock that produces periodic secretory pulses of GnRH, but how the timing of these pulses is determined is poorly understood. The neuropeptide kisspeptin potently and selectively stimulates the secretion of GnRH. Although this property of kisspeptin is well described, the effects of kisspeptin on endogenous GnRH pulse generation remain largely unexplored. Objective: The objective of the study was to detail the effects of kisspeptin on GnRH secretion, as reflected by LH secretion, in men. Participants: Thirteen healthy adult men participated in the study. Intervention: The intervention was the administration of a single iv bolus of the C-terminal decapeptide of kisspeptin (amino acids 112-121 of the parent protein). Results: Kisspeptin induced an immediate LH pulse, regardless of the timing of the previous endogenous pulse. The kisspeptin-induced pulses were on average larger than endogenous pulses (amplitude 5.0 +/- 1.0 vs. 2.1 +/- 0.3 mIU/ml, P = 0.02). Comparison of the morphology of kisspeptin-induced LH pulses in healthy men with that of GnRH-induced LH pulses in men with isolated GnRH deficiency suggests that a single iv bolus of kisspeptin triggered sustained GnRH release lasting approximately 17 min. Furthermore, kisspeptin reset the GnRH pulse generator, as it not only induced an immediate LH pulse but also delayed the next endogenous pulse by an interval approximating the normal interpulse interval. Conclusions: As the first known agent capable of resetting the hypothalamic GnRH pulse generator, kisspeptin can be used as a physiological tool for studying GnRH pulse generation and opens a door to understanding the mechanisms of biological clocks in general. (J Clin Endocrinol Metab 96: E908-E915, 2011) C1 [Chan, Yee-Ming; Pinnell, Nancy E.; Pralong, Francois P.; Crowley, William F., Jr.; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Harvard Reprod Sci Ctr, Boston, MA 02114 USA. [Chan, Yee-Ming; Pinnell, Nancy E.; Pralong, Francois P.; Crowley, William F., Jr.; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Chan, Yee-Ming] Childrens Hosp Boston, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Butler, James P.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Ren, Chen; Chan, Kenneth K.] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. RP Chan, YM (reprint author), Massachusetts Gen Hosp, Dept Med, Harvard Reprod Sci Ctr, 55 Fruit St,BHX 5, Boston, MA 02114 USA. EM ymchan@partners.org FU Eunice Kennedy Shriver National Institute for Child Health and Human Development [R01 HD43341]; National Center for Research Resources (Harvard Clinical and Translational Science Center) [UL1 RR025758]; Charles A. King Trust; Children's Hospital Boston FX This work was supported by Grant R01 HD43341 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development and Grant UL1 RR025758 (Harvard Clinical and Translational Science Center) from the National Center for Research Resources. Y.-M.C. was supported by a Charles A. King Trust postdoctoral fellowship and a Career Development Award from Children's Hospital Boston. NR 39 TC 44 Z9 44 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2011 VL 96 IS 6 BP E908 EP E915 DI 10.1210/jc.2010-3046 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 766TU UT WOS:000290810200005 PM 21470997 ER PT J AU Chadwick, EK Blana, D Simeral, JD Lambrecht, J Kim, SP Cornwell, AS Taylor, DM Hochberg, LR Donoghue, JP Kirsch, RF AF Chadwick, E. K. Blana, D. Simeral, J. D. Lambrecht, J. Kim, S. P. Cornwell, A. S. Taylor, D. M. Hochberg, L. R. Donoghue, J. P. Kirsch, R. F. TI Continuous neuronal ensemble control of simulated arm reaching by a human with tetraplegia SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID SPINAL-CORD-INJURY; FUNCTIONAL ELECTRICAL-STIMULATION; NEUROMUSCULAR STIMULATION; CORTICAL CONTROL; NEURAL-CONTROL; HAND; RESTORATION; COMPUTER; SYSTEM; MOVEMENT AB Functional electrical stimulation (FES), the coordinated electrical activation of multiple muscles, has been used to restore arm and hand function in people with paralysis. User interfaces for such systems typically derive commands from mechanically unrelated parts of the body with retained volitional control, and are unnatural and unable to simultaneously command the various joints of the arm. Neural interface systems, based on spiking intracortical signals recorded from the arm area of motor cortex, have shown the ability to control computer cursors, robotic arms and individual muscles in intact non-human primates. Such neural interface systems may thus offer a more natural source of commands for restoring dexterous movements via FES. However, the ability to use decoded neural signals to control the complex mechanical dynamics of a reanimated human limb, rather than the kinematics of a computer mouse, has not been demonstrated. This study demonstrates the ability of an individual with long-standing tetraplegia to use cortical neuron recordings to command the real-time movements of a simulated dynamic arm. This virtual arm replicates the dynamics associated with arm mass and muscle contractile properties, as well as those of an FES feedback controller that converts user commands into the required muscle activation patterns. An individual with long-standing tetraplegia was thus able to control a virtual, two-joint, dynamic arm in real time using commands derived from an existing human intracortical interface technology. These results show the feasibility of combining such an intracortical interface with existing FES systems to provide a high-performance, natural system for restoring arm and hand function in individuals with extensive paralysis. C1 [Chadwick, E. K.; Blana, D.; Lambrecht, J.; Cornwell, A. S.; Taylor, D. M.; Kirsch, R. F.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Simeral, J. D.; Hochberg, L. R.; Donoghue, J. P.] Rehabil R&D Serv, Ctr Restorat & Regenerat Med, Dept Vet Affairs, Providence, RI USA. [Kim, S. P.; Donoghue, J. P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Taylor, D. M.; Kirsch, R. F.] Louis Stokes VA Med Ctr, Cleveland, OH USA. [Simeral, J. D.; Hochberg, L. R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Hochberg, L. R.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hochberg, L. R.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Hochberg, L. R.] Harvard Univ, Sch Med, Dept Neurol, Spaulding Rehabil Hosp, Boston, MA 02115 USA. RP Chadwick, EK (reprint author), Aberystwyth Univ, Dept Sport & Exercise Sci, Aberystwyth, Dyfed, Wales. EM robert.kirsch@case.edu OI Chadwick, Edward/0000-0003-0877-5110; Blana, Dimitra/0000-0003-0488-6120 FU NICHD NIH HHS [N01 HD053403]; NIDCD NIH HHS [R01 DC009899, R01 DC009899-01, R01 DC009899-02] NR 27 TC 43 Z9 43 U1 2 U2 15 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD JUN PY 2011 VL 8 IS 3 AR 034003 DI 10.1088/1741-2560/8/3/034003 PG 7 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 769RE UT WOS:000291035100005 PM 21543840 ER PT J AU Freeman, DK Rizzo, JF Fried, SI AF Freeman, Daniel K. Rizzo, Joseph F., III Fried, Shelley I. TI Encoding visual information in retinal ganglion cells with prosthetic stimulation SO JOURNAL OF NEURAL ENGINEERING LA English DT Article; Proceedings Paper CT 6th Biennial Research Congress of the Eye and the Chip CY SEP, 2010 CL Detroit, MI ID TEMPORAL RESPONSE PROPERTIES; ISOLATED CHICKEN RETINA; ELECTRICAL-STIMULATION; PRIMATE RETINA; SACCADIC SUPPRESSION; IN-VITRO; RECEPTIVE-FIELDS; RABBIT RETINA; SPIKE TRAINS; RD1 MICE AB Retinal prostheses aim to restore functional vision to those blinded by outer retinal diseases using electric stimulation of surviving retinal neurons. The ability to replicate the spatiotemporal pattern of ganglion cell spike trains present under normal viewing conditions is presumably an important factor for restoring high-quality vision. In order to replicate such activity with a retinal prosthesis, it is important to consider both how visual information is encoded in ganglion cell spike trains, and how retinal neurons respond to electric stimulation. The goal of the current review is to bring together these two concepts in order to guide the development of more effective stimulation strategies. We review the experiments to date that have studied how retinal neurons respond to electric stimulation and discuss these findings in the context of known retinal signaling strategies. The results from such in vitro studies reveal the advantages and disadvantages of activating the ganglion cell directly with the electric stimulus (direct activation) as compared to activation of neurons that are presynaptic to the ganglion cell (indirect activation). While direct activation allows high temporal but low spatial resolution, indirect activation yields improved spatial resolution but poor temporal resolution. Finally, we use knowledge gained from in vitro experiments to infer the patterns of elicited activity in ongoing human trials, providing insights into some of the factors limiting the quality of prosthetic vision. C1 [Freeman, Daniel K.; Rizzo, Joseph F., III; Fried, Shelley I.] Boston VA Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. [Freeman, Daniel K.; Fried, Shelley I.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Freeman, Daniel K.; Rizzo, Joseph F., III; Fried, Shelley I.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Freeman, DK (reprint author), Boston VA Healthcare Syst, Ctr Innovat Visual Rehabil, 150 S Huntington Ave, Boston, MA 02130 USA. EM dfreeman@mit.edu; Fried.Shelley@mgh.harvard.edu FU NEI NIH HHS [R01 EY019967-01, R01 EY019967, R01 EY-019967-01] NR 150 TC 17 Z9 18 U1 5 U2 15 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD JUN PY 2011 VL 8 IS 3 AR 035005 DI 10.1088/1741-2560/8/3/035005 PG 18 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 769RE UT WOS:000291035100012 PM 21593546 ER PT J AU Jeng, J Tang, S Molnar, A Desai, NJ Fried, SI AF Jeng, J. Tang, S. Molnar, A. Desai, N. J. Fried, S. I. TI The sodium channel band shapes the response to electric stimulation in retinal ganglion cells SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID AXON INITIAL SEGMENT; MORPHOMETRIC-ANALYSIS; RETINITIS-PIGMENTOSA; ACTIVATION; NEURONS; MICROELECTRODE; DEGENERATION; PRESERVATION; PROSTHESIS; MOUSE AB To improve the quality of prosthetic vision, it is desirable to understand how targeted retinal neurons respond to stimulation. Unfortunately, the factors that shape the response of a single neuron to stimulation are not well understood. A dense band of voltage-gated sodium channels within the proximal axon of retinal ganglion cells is the site most sensitive to electric stimulation, suggesting that band properties are likely to influence the response to stimulation. Here, we examined how three band properties influence sensitivity using a morphologically realistic ganglion cell model in NEURON. Longer bands were more sensitive to short-duration pulses than shorter bands and increasing the distance between band and soma also increased sensitivity. Simulations using the known limits of band length and location resulted in a sensitivity difference of approximately 2. Additional simulations tested how changes to sodium channel conductance within the band influenced threshold and found that the sensitivity difference increased to a factor of nearly 3. This is close to the factor of 5 difference measured in physiological studies suggesting that band properties contribute significantly to the sensitivity differences found between different types of retinal neurons. C1 [Jeng, J.; Desai, N. J.; Fried, S. I.] Boston VA Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. [Jeng, J.; Desai, N. J.; Fried, S. I.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Jeng, J.; Desai, N. J.; Fried, S. I.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tang, S.] Univ Calif, Dept Nat Sci, Merced, CA 95348 USA. [Tang, S.; Molnar, A.] Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY 14853 USA. RP Jeng, J (reprint author), Boston VA Healthcare Syst, Ctr Innovat Visual Rehabil, 150 S Huntington Ave, Boston, MA 02130 USA. EM fried.shelley@mgh.harvard.edu FU NEI NIH HHS [1 R01 EY019967-01, R01 EY019967, R01 EY019967-01] NR 35 TC 15 Z9 16 U1 1 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD JUN PY 2011 VL 8 IS 3 AR 036022 DI 10.1088/1741-2560/8/3/036022 PG 12 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 769RE UT WOS:000291035100034 PM 21558602 ER PT J AU Jensen, RJ Rizzo, JF AF Jensen, Ralph J. Rizzo, Joseph F., III TI Effects of GABA receptor antagonists on thresholds of P23H rat retinal ganglion cells to electrical stimulation of the retina SO JOURNAL OF NEURAL ENGINEERING LA English DT Article; Proceedings Paper CT 6th Biennial Research Congress of the Eye and the Chip CY SEP, 2010 CL Detroit, MI ID ROD BIPOLAR CELLS; PHOTORECEPTOR DEGENERATION; MOUSE RETINA; SLICE PREPARATION; MAMMALIAN RETINA; TRANSGENIC RAT; AMACRINE CELLS; RHO-SUBUNITS; RD10 MOUSE; RCS RATS AB An electronic retinal prosthesis may provide useful vision for patients suffering from retinitis pigmentosa (RP). In animal models of RP, the amount of current needed to activate retinal ganglion cells (RGCs) is higher than in normal, healthy retinas. In this study, we sought to reduce the stimulation thresholds of RGCs in a degenerate rat model (P23H-line 1) by blocking GABA receptor mediated inhibition in the retina. We examined the effects of TPMPA, a GABA(C) receptor antagonist, and SR95531, a GABA(A) receptor antagonist, on the electrically evoked responses of RGCs to biphasic current pulses delivered to the subretinal surface through a 400 mu m diameter electrode. Both TPMPA and SR95531 reduced the stimulation thresholds of ON-center RGCs on average by 15% and 20% respectively. Co-application of the two GABA receptor antagonists had the greatest effect, on average reducing stimulation thresholds by 32%. In addition, co-application of the two GABA receptor antagonists increased the magnitude of the electrically evoked responses on average three-fold. Neither TPMPA nor SR95531, applied alone or in combination, had consistent effects on the stimulation thresholds of OFF-center RGCs. We suggest that the effects of the GABA receptor antagonists on ON-center RGCs may be attributable to blockage of GABA receptors on the axon terminals of ON bipolar cells. C1 [Jensen, Ralph J.; Rizzo, Joseph F., III] VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. [Rizzo, Joseph F., III] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Jensen, RJ (reprint author), VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Mail Stop 151E,150 S Huntington Ave, Boston, MA 02130 USA. EM Ralph.jensen@va.gov NR 45 TC 4 Z9 4 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD JUN PY 2011 VL 8 IS 3 AR 035002 DI 10.1088/1741-2560/8/3/035002 PG 8 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 769RE UT WOS:000291035100009 PM 21593547 ER PT J AU Suva, M Chi, A Rheinbay, E Wakimoto, H Rivera, M Oksuz, O Rabkin, S Martuza, R Louis, D Bernstein, B AF Suva, Mario Chi, Andrew Rheinbay, Esther Wakimoto, Hiro Rivera, Miguel Oksuz, Ozgur Rabkin, Samuel Martuza, Robert Louis, David Bernstein, Bradley TI Genome-Wide Chromatin Landscape of Glioblastoma Cancer Stem Cells Highlights an Aberrant Network of Transcription Factors SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 87th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 23-26, 2011 CL Seattle, WA SP Amer Assoc Neuropathologists C1 [Suva, Mario; Rheinbay, Esther; Rivera, Miguel; Oksuz, Ozgur; Louis, David; Bernstein, Bradley] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chi, Andrew] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wakimoto, Hiro; Rabkin, Samuel; Martuza, Robert] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2011 VL 70 IS 6 MA 2 BP 498 EP 498 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 766AV UT WOS:000290751700011 ER PT J AU William, C Shatz, C Frosch, M Hyman, B AF William, Christopher Shatz, Carla Frosch, Matthew Hyman, Bradley TI Ocular Dominance Plasticity Defect in Alzheimer Disease Model Mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 87th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 23-26, 2011 CL Seattle, WA SP Amer Assoc Neuropathologists C1 [William, Christopher; Frosch, Matthew] Massachusetts Gen Hosp, Neuropathol Serv, Boston, MA 02114 USA. [Shatz, Carla] Stanford Univ, Stanford, CA 94305 USA. [Hyman, Bradley] MGH, MassGen Inst Neurodegenerat Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2011 VL 70 IS 6 MA 12 BP 501 EP 501 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 766AV UT WOS:000290751700021 ER PT J AU Stein, T Dols, O Scotton, T Da Rocha-Souto, B Alberto, SP Matthew, F John, G Bradley, H Teresa, GI AF Stein, Thor Dols, Oriol Scotton, Thomas Da Rocha-Souto, Bibiana Alberto, Serrano-Pozo Matthew, Frosch John, Growdon Bradley, Hyman Teresa, Gomez-Isla TI Characterization of Human Brains Resilient to beta-amyloid and Tau Pathologies SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 87th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 23-26, 2011 CL Seattle, WA SP Amer Assoc Neuropathologists C1 [Stein, Thor; Dols, Oriol; Scotton, Thomas; Da Rocha-Souto, Bibiana; Alberto, Serrano-Pozo; Matthew, Frosch; John, Growdon; Bradley, Hyman; Teresa, Gomez-Isla] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2011 VL 70 IS 6 MA 15 BP 502 EP 502 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 766AV UT WOS:000290751700024 ER PT J AU Auluck, P Lindquist, S AF Auluck, Pavan Lindquist, Susan TI The Relationship Between Mitochondrial Dysfunction and Alpha-Synuclein in a Yeast Model of Alpha-Synucleinopathies SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 87th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 23-26, 2011 CL Seattle, WA SP Amer Assoc Neuropathologists C1 [Auluck, Pavan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lindquist, Susan] HHMI, Whitehead Inst Biomed Res, Chevy Chase, MD USA. [Lindquist, Susan] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2011 VL 70 IS 6 MA 32 BP 506 EP 507 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 766AV UT WOS:000290751700041 ER PT J AU Stemmer-Rachamimov, A Camelo-Piragua, S Plotkin, S AF Stemmer-Rachamimov, Anat Camelo-Piragua, Sandra Plotkin, Scott TI Mutant Isocitrate Dehydrogenase 1 Immunohistochemistry: Not Useful in the Diagnosis of Low Grade Diffuse Astrocytomas in NF1 SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 87th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 23-26, 2011 CL Seattle, WA SP Amer Assoc Neuropathologists C1 [Stemmer-Rachamimov, Anat; Camelo-Piragua, Sandra; Plotkin, Scott] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2011 VL 70 IS 6 MA 51 BP 511 EP 511 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 766AV UT WOS:000290751700060 ER PT J AU Snuderl, M Sheth, S Wirth, D Ogas, P Kwon, CS Curry, W Frosch, M Yaroslavsky, A AF Snuderl, Matija Sheth, Sameer Wirth, Dennis Ogas, Polina Kwon, Churl-Su Curry, William Frosch, Matthew Yaroslavsky, Anna TI Dye-Enhanced Multimodal Confocal Imaging as a Novel Approach to Intraoperative Diagnosis of Brain Tumors SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 87th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 23-26, 2011 CL Seattle, WA SP Amer Assoc Neuropathologists C1 [Snuderl, Matija; Frosch, Matthew] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sheth, Sameer; Ogas, Polina; Kwon, Churl-Su; Curry, William] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Wirth, Dennis] Univ Massachusetts, Dept Phys & Appl Phys, Amherst, MA 01003 USA. [Yaroslavsky, Anna] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2011 VL 70 IS 6 MA 110 BP 527 EP 527 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 766AV UT WOS:000290751700119 ER PT J AU Davidson, C Plotkin, S Stemmer-Rachamimov, A AF Davidson, Christian Plotkin, Scott Stemmer-Rachamimov, Anat TI Diffusely Infiltrative Plexiform Schwannoma in Two Patients With Neurofibromatosis Type 2 SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 87th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 23-26, 2011 CL Seattle, WA SP Amer Assoc Neuropathologists C1 [Davidson, Christian; Plotkin, Scott; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2011 VL 70 IS 6 MA 159 BP 540 EP 540 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 766AV UT WOS:000290751700168 ER PT J AU Heras, FL Stemmer-Rachamimov, A AF Heras, Facundo Las Stemmer-Rachamimov, Anat TI Hybrid Schwannoma/Perineurioma of the VIII Cranial Nerve: Case Report SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 87th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 23-26, 2011 CL Seattle, WA SP Amer Assoc Neuropathol C1 [Heras, Facundo Las] Univ Chile, Clin Hosp, Santiago, Chile. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2011 VL 70 IS 6 BP 541 EP + PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 766AV UT WOS:000290751700172 ER PT J AU Courtwright, AM Laughon, MM Doron, MW AF Courtwright, A. M. Laughon, M. M. Doron, M. W. TI Length of life and treatment intensity in infants diagnosed prenatally or postnatally with congenital anomalies considered to be lethal SO JOURNAL OF PERINATOLOGY LA English DT Article DE congenital malformation; pregnancy termination; intensive care; decision making; ethics; lethal ID TRISOMY-18; MANAGEMENT; MALFORMATIONS; MORTALITY; FETAL AB Objectives: The objectives of this study were (1) to compare age at death and the intensity and cost of medical treatment for infants diagnosed prenatally or postnatally with congenital anomalies considered to be lethal. (2) To determine whether greater treatment intensity is associated with longer life. Study Design: This is a retrospective cohort study of all fetuses and neonates with congenital anomalies classified as lethal who were diagnosed or treated at the University of North Carolina Hospitals from January 1998 to December 2003. Result: The cohort consisted of 192 fetuses and infants: 160 were diagnosed prenatally, 2 were diagnosed perinatally, and 30 were diagnosed postnatally. In all, 115 (72%) pregnancies were terminated. Of the liveborn infants, 75% died before 10 days of age and 90% before 4 months of age. Compared with postnatally diagnosed infants, prenatally diagnosed infants received less intense treatment (median average daily Neonatal Therapeutic Intervention Scoring System score 8.3 versus 14.0; P = 0.02), at less cost (median direct cost of hospitalization $1550 versus $8474; P = 0.03) and died sooner (median age at death <1 day versus 4 days; P = 0.01). Greater treatment intensity did not correlate with longer survival (r = -0.04; P = 0.66). Conclusion: Although some kinds of medical therapy may be appropriate for newborns with lethal congenital anomalies, highly aggressive interventions did not prolong survival and should not be offered. Even when pregnancy termination is not elected, infants diagnosed prenatally receive less intense care. Journal of Perinatology (2011) 31, 387-391; doi:10.1038/jp.2010.124; published online 16 December 2010 C1 [Courtwright, A. M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Laughon, M. M.; Doron, M. W.] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA. RP Doron, MW (reprint author), UNC Hosp, Dept Pediat, CB 7596, Chapel Hill, NC 27599 USA. EM mia_doron@med.unc.edu FU Howard Holderness Medical Fellowship Grant FX We thank Carl Bose, Cynthia Cassell, Michael McDade, Robert Meyer, Kelly Gilmore, Emily Hardisty, Anthony Johnson, Kenneth Moise, Cynthia Powell, Ben Saville, Kathleen Veness-Meehan and Honor Wolfe for their help with this project. Salary support for Andrew Courtwright was provided by a Howard Holderness Medical Fellowship Grant. NR 28 TC 16 Z9 16 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD JUN PY 2011 VL 31 IS 6 BP 387 EP 391 DI 10.1038/jp.2010.124 PG 5 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 769NX UT WOS:000291024300002 PM 21164425 ER PT J AU Cadge, W Calle, K Dillinger, J AF Cadge, Wendy Calle, Katherine Dillinger, Jennifer TI What Do Chaplains Contribute to Large Academic Hospitals? The Perspectives of Pediatric Physicians and Chaplains SO JOURNAL OF RELIGION & HEALTH LA English DT Article DE Chaplains; Chaplaincy; Pediatric physicians; Spiritual care ID UNITED-STATES; HEALTH-CARE; SPIRITUALITY; RELIGION; PROVISION; MEDICINE; BELIEFS AB This article analyzes interviews with pediatric physicians (N = 30) and chaplains (N = 22) who work at the same large academic medical centers (N = 13). We ask how pediatric physicians understand and work with chaplains and how chaplains describe their own work. We find that physicians see chaplains as part of interdisciplinary medical teams where they perform rituals and support patients and families, especially around death. Chaplains agree but frame their contributions in terms of the perspectives related to wholeness, presence, and healing they bring. Chaplains have a broader sense of what they contribute to patient care than do physicians. C1 [Cadge, Wendy] Brandeis Univ, Dept Sociol, Waltham, MA 02454 USA. [Calle, Katherine] Harvard Univ, Cambridge, MA 02138 USA. [Dillinger, Jennifer] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cadge, W (reprint author), Brandeis Univ, Dept Sociol, MS 071, Waltham, MA 02454 USA. EM wcadge@brandeis.edu NR 53 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-4197 J9 J RELIG HEALTH JI J. Relig. Health PD JUN PY 2011 VL 50 IS 2 BP 300 EP 312 DI 10.1007/s10943-011-9474-8 PG 13 WC Public, Environmental & Occupational Health; Religion SC Public, Environmental & Occupational Health; Religion GA 763RV UT WOS:000290578300010 PM 21409483 ER PT J AU Yared, K Noseworthy, P Weyman, AE McCabe, E Picard, MH Baggish, AL AF Yared, Kibar Noseworthy, Peter Weyman, Arthur E. McCabe, Elizabeth Picard, Michael H. Baggish, Aaron L. TI Pulmonary Artery Acceleration Time Provides an Accurate Estimate of Systolic Pulmonary Arterial Pressure during Transthoracic Echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Pulmonary artery acceleration time; Right ventricular systolic pressure; Pulmonary artery pressure; Transthoracic echocardiography ID SALINE CONTRAST ENHANCEMENT; TRICUSPID REGURGITATION; NONINVASIVE ESTIMATION; DOPPLER ULTRASOUND; CATHETERIZATION; HYPERTENSION; VELOCITY AB Background: Transthoracic echocardiographic estimates of peak systolic pulmonary artery pressure are conventionally calculated from the maximal velocity of the tricuspid regurgitation (TR) jet. Unfortunately, there is insufficient TR to determine estimated peak systolic pulmonary artery pressure (EPSPAP) in a significant number of patients. To date, in the absence of TR, no noninvasive method of deriving EPSPAP has been developed. Methods: Five hundred clinically indicated transthoracic echocardiograms were reviewed over a period of 6 months. Patients with pulmonic stenosis were excluded. Pulsed-wave Doppler was used to measure pulmonary artery acceleration time (PAAT) and right ventricular ejection time. Continuous-wave Doppler was used to measure the peak velocity of TR (TR(Vmax)), and EPSPAP was calculated as 4 -TR(Vmax)2 + 10mmHg (to account for right atrial pressure). The relationship between PAAT and EPSPAP was then assessed. Results: Adequate imaging to measure PAAT was available in 99.6% of patients (498 of 500), but 25.3% (126 of 498) had insufficient TR to determine EPSPAP, and 1 patient had significant pulmonic stenosis. Therefore, 371 were included in the final analysis. Interobserver variability for PAAT was 0.97. There were strong inverse correlations between PAAT and TRVmax (r = -0.96), the right atrial/right ventricular pressure gradient (r = -0.95), and EPSPAP (r = -0.95). The regression equation describing the relationship between PAAT and EPSPAP was log(10)(EPSPAP) = -0.004 (PAAT) + 2.1 (P <.001). Conclusions: PAAT is routinely obtainable and correlates strongly with both TRVmax and EPSPAP in a large population of randomly selected patients undergoing transthoracic echocardiography. Characterization of the relationship between PAAT and EPSPAP permits PAAT to be used to estimate peak systolic pulmonary artery pressure independent of TR, thereby increasing the percentage of patients in whom transthoracic echocardiography can be used to quantify pulmonary artery pressure. (J Am Soc Echocardiogr 2011; 24:687-92.) C1 [Yared, Kibar] Univ Toronto, Sch Med, Div Cardiol, Scarborough Hosp, Toronto, ON M1P 2V5, Canada. [Yared, Kibar; Noseworthy, Peter; Weyman, Arthur E.; McCabe, Elizabeth; Picard, Michael H.; Baggish, Aaron L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Yared, K (reprint author), Univ Toronto, Sch Med, Div Cardiol, Scarborough Hosp, Gen Campus,3050 Lawrence Ave W, Toronto, ON M1P 2V5, Canada. EM kibaryared@yahoo.com OI Picard, Michael/0000-0002-9264-3243 NR 27 TC 50 Z9 53 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JUN PY 2011 VL 24 IS 6 BP 687 EP 692 DI 10.1016/j.echo.2011.03.008 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 768OI UT WOS:000290944100012 PM 21511434 ER PT J AU Yeramian, A Santacana, M Sorolla, A Llobet, D Encinas, M Velasco, A Bahi, N Eritja, N Domingo, M Oliva, E Dolcet, X Matias-Guiu, X AF Yeramian, Andree Santacana, Maria Sorolla, Anabel Llobet, David Encinas, Mario Velasco, Ana Bahi, Nuria Eritja, Nuria Domingo, Monica Oliva, Esther Dolcet, Xavier Matias-Guiu, Xavier TI Nuclear factor-kappa B2/p100 promotes endometrial carcinoma cell survival under hypoxia in a HIF-1 alpha independent manner SO LABORATORY INVESTIGATION LA English DT Article DE apoptosis; hypoxia; IKK alpha; IKK beta; NF-kappa B ID NF-KAPPA-B; IKK-ALPHA; NF-KAPPA-B2 P100; GENE-EXPRESSION; INDUCIBLE FACTOR-1-ALPHA; PROTEASOME INHIBITORS; IMMUNE-RESPONSES; KINASE-ALPHA; CANCER CELLS; ACTIVATION AB Endometrial carcinoma (EC) is a common female cancer, treated mainly by surgery and adjuvant radiotherapy. Relapse following treatment is associated with increased risk of metastases. Hypoxia, a common microenvironment in solid tumors, correlates with malignant progression, rendering tumors resistant to ionizing therapy. Hence, we assessed here the immunohistochemical expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and members of the NF-kappa B family in 82 primary EC and 10 post-radiation recurrences of EC. Post-radiation recurrences were highly hypoxic, with a higher expression of HIF-1 alpha and also RelA (p65) and p52 when compared with primary EC. We next investigated the effects of hypoxia on EC cell lines. We found that EC cell lines are highly resistant to hypoxia-induced apoptosis. We thus focused on the molecular mechanisms involved in conferring hypoxic cell death resistance. We show that in addition to the classical NF-kappa B, hypoxia activates the alternative NF-kappa B pathway. To characterize the upstream kinases involved in the activation of these pathways, we used lentiviral-mediated knockdown and mouse embryonic fibroblasts lacking IKK alpha and IKK beta kinases. Both IKK alpha and IKK beta kinases are required for RelA (p65) and p100 accumulation, whereas p52 processing under hypoxia is IKK alpha dependent. Furthermore, Ishikawa endometrial cell line harboring either RelA (p65) or p52 short-hairpin RNA was sensitive to hypoxia-induced cell death, indicating that, in addition to the known prosurvival role of RelA (p65) under hypoxia, alternative NF-kappa B pathway also enhances hypoxic survival of EC cells. Interestingly, although HIF-1 alpha controlled classical NF-kappa B activation pathway and survival under hypoxia through RelA (p65) nuclear accumulation, the alternative pathway was HIF-1 alpha independent. These findings have important clinical implications for the improvement of EC prognosis before radiotherapy. Laboratory Investigation (2011) 91, 859-871; doi:10.1038/labinvest.2011.58; published online 2 May 2011 C1 [Yeramian, Andree; Santacana, Maria; Sorolla, Anabel; Llobet, David; Velasco, Ana; Bahi, Nuria; Eritja, Nuria; Domingo, Monica; Dolcet, Xavier; Matias-Guiu, Xavier] Univ Lleida, Hosp Univ Arnau Vilanova, Inst Recerca Biomed Lleida, Dept Pathol & Mol Genet,Lab Recerca Biomed, Ileida, Spain. [Encinas, Mario] IRBLleida, Dept Expt Med, Ileida, Spain. [Oliva, Esther] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yeramian, A (reprint author), Univ Lleida, Hosp Univ Arnau Vilanova, Inst Recerca Biomed Lleida, Dept Pathol & Mol Genet,Lab Recerca Biomed, Av Rovira Roure 80, Lleida 25198, Spain. EM andree.yeramian@cmb.udl.es RI Llobet-Navas, David/B-5660-2009; Bahi Pla, Nuria/B-8022-2009; Eritja Sanchez, Nuria/C-4465-2011; Encinas, Mario/B-5600-2009; matias-guiu, xavier/C-3039-2009; Dolcet, Xavi/B-5665-2009; Sorolla, Anabel/E-2546-2012; eritja, Nuria/M-1347-2015 OI Llobet-Navas, David/0000-0003-1443-7003; Bahi Pla, Nuria/0000-0003-2845-0313; Encinas, Mario/0000-0003-3509-7431; matias-guiu, xavier/0000-0002-7201-6605; eritja, Nuria/0000-0003-1018-6649 FU Ministerio de Educacion y Ciencia (Juan de la Cierva) [RD 06/00/20/134, 2009 SGR 174, Fis PI070276]; Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo [CP05/00028, FI05/00191, FI08/0012]; Fundacion Cientifica AECC, Catalunya contra el Cancer, Lleida FX We thank Concepcio Soler and Jordi Torres for critical reading of the manuscript. We thank Dr Michael Karin for providing IKK alpha-/- and IKK beta-/- MEFs. This work was supported by grants from RD 06/00/20/134, 2009 SGR 174, Fis PI070276, Ministerio de Educacion y Ciencia (Juan de la Cierva Postdoctoral fellowship to AY), the Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo (Postdoctoral fellowship CP05/00028 to XD and Predoctoral fellowships FI05/00191 to DL and FI08/0012 to NE), Fundacion Cientifica AECC, Catalunya contra el Cancer, Lleida (fellowship to AS). Tumor samples were obtained with the support of Xarxa Catalana de Bancs de Tumors, The Tumor Banc Platform of RTICC and RD09/0076/000S9. This work is dedicated to Daniel, Alfonso and Irene. NR 44 TC 17 Z9 18 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUN PY 2011 VL 91 IS 6 BP 859 EP 871 DI 10.1038/labinvest.2011.58 PG 13 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 769OO UT WOS:000291026300006 PM 21537326 ER PT J AU Hughes, KS Roche, CA AF Hughes, Kevin S. Roche, Constance A. TI The complexity of breast cancer risk needs to be embraced, not oversimplified SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID TAMOXIFEN C1 [Hughes, Kevin S.; Roche, Constance A.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Hughes, KS (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. OI Hughes, Kevin/0000-0003-4084-6484 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 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUN PY 2011 VL 18 IS 6 BP 599 EP 600 DI 10.1097/gme.0b013e31821bbd55 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 769HV UT WOS:000291004400003 PM 21587090 ER PT J AU Seldin, E AF Seldin, Edward TI The interconnectedness of medical and dental health SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Seldin, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUN PY 2011 VL 18 IS 6 BP 601 EP 602 DI 10.1097/gme.0b013e3182113bff PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 769HV UT WOS:000291004400004 PM 21403581 ER PT J AU Jessup, JA Zhang, LL Chen, AF Presley, TD Kim-Shapiro, DB Chappell, MC Wang, H Groban, L AF Jessup, Jewell A. Zhang, Lili Chen, Alex F. Presley, Tennille D. Kim-Shapiro, Daniel B. Chappell, Mark C. Wang, Hao Groban, Leanne TI Neuronal nitric oxide synthase inhibition improves diastolic function and reduces oxidative stress in ovariectomized mRen2.Lewis rats SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Diastolic function; Fibrosis; Left ventricular modeling; Myocardial relaxation; Nitric oxide; Postmenopausal ID LEFT-VENTRICULAR HYPERTROPHY; HEART-FAILURE; POSTMENOPAUSAL WOMEN; VASCULAR TETRAHYDROBIOPTERIN; PRESSURE-OVERLOAD; SYSTOLIC FUNCTION; RECEPTOR BLOCKER; BLOOD-PRESSURE; ADVANCED-STAGE; ESTROGEN AB Objective: The loss of estrogen in mRen2.Lewis rats leads to an exacerbation of diastolic dysfunction. Because specific neuronal nitric oxide synthase (nNOS) inhibition reverses renal damage in the same model, we assessed the effects of inhibiting neuronal nitric oxide on diastolic function, left ventricular remodeling, and the components of the cardiac nitric oxide system in ovariectomized (OVX) and sham-operated mRen2.Lewis rats treated with N(5)-(1-imino-3-butenyl)-L-ornithine (L-VNIO; 0.5 mg/kg per day for 28 d) or vehicle (saline). Methods: Female mRen2.Lewis rats underwent either bilateral oophorectomy (OVX; n = 15) or sham operation (or surgical procedure) (sham; n = 19) at 4 weeks of age. Beginning at 11 weeks of age, the rats were randomized to receive either L-VNIO or vehicle. Results: The surgical loss of ovarian hormones, particularly estrogen, led to exacerbated hypertension, impaired myocardial relaxation, diminished diastolic compliance, increased perivascular fibrosis, and increased relative wall thickness. The cardiac tetrahydrobiopterin-to-dihydrobiopterin levels were lower among OVX rats compared with sham-operated rats, and this altered cardiac biopterin profile was associated with enhanced myocardial superoxide production and decreased nitric oxide release. L-VNIO decreased myocardial reactive oxygen species production, increased nitrite concentrations, attenuated cardiac remodeling, and improved diastolic function. Conclusions: Impaired relaxation, diastolic stiffness, and cardiac remodeling were found among OVX mRen2.Lewis rats. A possible mechanism for this unfavorable cardiac phenotype may have resulted from a deficiency in available tetrahydrobiopterin and subsequent increase in nNOS-derived superoxide and reduction in nitric oxide synthase metabolites within the heart. Selective nNOS inhibition with L-VNIO attenuated cardiac superoxide production and limited remodeling, leading to improved diastolic function in OVX mRen2.Lewis rats. C1 [Wang, Hao; Groban, Leanne] Wake Forest Univ, Dept Anesthesiol, Sch Med, Winston Salem, NC 27157 USA. [Jessup, Jewell A.; Groban, Leanne] Wake Forest Univ, Dept Physiol & Pharmacol, Sch Med, Winston Salem, NC 27157 USA. [Zhang, Lili; Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Chen, Alex F.] Vet Affairs Pittsburgh Healthcare Syst, Vasc Surg Res, Pittsburgh, PA USA. [Presley, Tennille D.; Kim-Shapiro, Daniel B.] Winston Salem State Univ, Dept Chem, Winston Salem, NC USA. [Kim-Shapiro, Daniel B.] Wake Forest Univ, Translat Sci Ctr, Winston Salem, NC 27157 USA. [Chappell, Mark C.] Wake Forest Univ, Hypertens & Vasc Res Ctr, Sch Med, Winston Salem, NC 27157 USA. RP Groban, L (reprint author), Wake Forest Univ, Dept Anesthesiol, Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM lgroban@wfubmc.edu FU National Institutes of Health [R01-AG033727-01, K08-AG026764-05, HL058091, R01 GM077352, HL-56973]; American Heart Association [0855601GH] FX The work described here was supported in part by grants from the National Institutes of Health R01-AG033727-01 (L.G.), K08-AG026764-05 Paul Beeson Award (L.G.), National Institutes of Health HL058091 (D.B.K.-S.), R01 GM077352 (A.F.C.), HL-56973 (M.C.C.), and American Heart Association Grant-in-Aid 0855601GH (A.F.C.). NR 53 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUN PY 2011 VL 18 IS 6 BP 698 EP 708 DI 10.1097/gme.0b013e31820390a2 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 769HV UT WOS:000291004400018 PM 21293310 ER PT J AU Aronis, KN Kim, YB Mantzoros, CS AF Aronis, Konstantinos N. Kim, Young-Bum Mantzoros, Christos S. TI Clusterin (apolipoprotein J): wither link with diabetes and cardiometabolic risk? SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID CORONARY-HEART-DISEASE; RETE TESTIS FLUID; PROSTATE-CANCER; EXPRESSION; DENSITY; OVEREXPRESSION; PURIFICATION; PROGRESSION; BIOMARKER; SURVIVAL C1 [Aronis, Konstantinos N.; Kim, Young-Bum; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Internal Med,Sect Endocrinol, Boston, MA 02215 USA. RP Aronis, KN (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012 OI Aronis, Konstantinos/0000-0001-7189-8434 NR 21 TC 5 Z9 5 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 JUN PY 2011 VL 60 IS 6 BP 747 EP 748 DI 10.1016/j.metabol.2010.12.013 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 770GX UT WOS:000291076100001 PM 21333309 ER PT J AU Magkos, F Mantzoros, CS AF Magkos, Faidon Mantzoros, Christos S. TI Body fat redistribution and metabolic abnormalities in HIV-infected patients on highly active antiretroviral therapy: novel insights into pathophysiology and emerging opportunities for treatment SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID RECOMBINANT HUMAN LEPTIN; INSULIN-RESISTANCE; ADIPOSE-TISSUE; LIPODYSTROPHY SYNDROME; CARDIOVASCULAR RISK; LIPOPROTEIN-LIPASE; LIPOATROPHY; DYSLIPIDEMIA; MEN; LIPOLYSIS C1 [Magkos, Faidon; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Boston VA Healthcare Syst, Sch Med, Endocrinol Sect, Boston, MA 02215 USA. RP Magkos, F (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu FU NIA NIH HHS [AG032030, R01 AG032030, R01 AG032030-01A1]; NIDDK NIH HHS [R56 DK058785, DK79929, DK81913, K24 DK081913-02, R01 DK058785, R01 DK079929-02, DK58785, K24 DK081913, R01 DK058785-02, R01 DK079929] NR 45 TC 20 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUN PY 2011 VL 60 IS 6 BP 749 EP 753 DI 10.1016/j.metabol.2010.09.011 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 770GX UT WOS:000291076100002 PM 20965525 ER PT J AU Murai, J Yang, KL Dejsuphong, D Hirota, K Takeda, S D'Andrea, AD AF Murai, Junko Yang, Kailin Dejsuphong, Donniphat Hirota, Kouji Takeda, Shunichi D'Andrea, Alan D. TI The USP1/UAF1 Complex Promotes Double-Strand Break Repair through Homologous Recombination SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FANCONI-ANEMIA PATHWAY; CROSS-LINK REPAIR; DNA-DAMAGE RESPONSE; POLY(ADP-RIBOSE) POLYMERASE; VERTEBRATE CELLS; GENOMIC INSTABILITY; BRCA1 DEFICIENCY; UBIQUITIN; INHIBITION; PROTEIN AB Protein ubiquitination plays a key role in the regulation of a variety of DNA repair mechanisms. Protein ubiquitination is controlled by the coordinate activity of ubiquitin ligases and deubiquitinating enzymes (DUBs). The deubiquitinating enzyme USP1 regulates DNA repair and the Fanconi anemia pathway through its association with its WD40 binding partner, UAF1, and through its deubiquitination of two critical DNA repair proteins, FANCD2-Ub and PCNA-Ub. To investigate the function of USP1 and UAF1, we generated USP1(-/-), UAF1(-/-/-), and USP1(-/-) UAF1(-/-/-) chicken DT40 cell clones. These three clones showed similar sensitivities to chemical cross-linking agents, to a topoisomerase poison, camptothecin, and to an inhibitor of poly(ADP-ribose) polymerase (PARP), indicating that the USP1/UAF1 complex is a regulator of the cellular response to DNA damage. The hypersensitivity to both camptothecin and a PARP inhibitor suggests that the USP1/UAF1 complex promotes homologous recombination (HR)-mediated double-strand break (DSB) repair. To gain insight into the mechanism of the USP1/UAF1 complex in HR, we inactivated the nonhomologous end-joining (NHEJ) pathway in UAF1-deficient cells. Disruption of NHEJ in UAF1-deficient cells restored cellular resistance to camptothecin and the PARP inhibitor. Our results indicate that the USP1/UAF1 complex promotes HR, at least in part by suppressing NHEJ. C1 [Murai, Junko; Yang, Kailin; Dejsuphong, Donniphat; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Murai, Junko; Hirota, Kouji; Takeda, Shunichi] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Sakyo Ku, Kyoto 6068501, Japan. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu RI Yang, Kailin/D-7966-2013; Yang, Kailin/L-2205-2013 OI Yang, Kailin/0000-0001-5968-6738 FU TOYOBO Biotechnology Foundation; NIH [P01CA092584, R01DK43889, R01HL52725] FX J.M. was funded by long-term research grants from the TOYOBO Biotechnology Foundation. K.Y. is a Harvard University Presidential Scholar. This work was supported by NIH grants P01CA092584, R01DK43889, and R01HL52725 to A.D.D. NR 45 TC 51 Z9 56 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2011 VL 31 IS 12 BP 2462 EP 2469 DI 10.1128/MCB.05058-11 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 769KA UT WOS:000291010100010 PM 21482670 ER PT J AU Freedman, ML Monteiro, ANA Gayther, SA Coetzee, GA Risch, A Plass, C Casey, G De Biasi, M Carlson, C Duggan, D James, M Liu, PY Tichelaar, JW Vikis, HG You, M Mills, IG AF Freedman, Matthew L. Monteiro, Alvaro N. A. Gayther, Simon A. Coetzee, Gerhard A. Risch, Angela Plass, Christoph Casey, Graham De Biasi, Mariella Carlson, Chris Duggan, David James, Michael Liu, Pengyuan Tichelaar, Jay W. Vikis, Haris G. You, Ming Mills, Ian G. TI Principles for the post-GWAS functional characterization of cancer risk loci SO NATURE GENETICS LA English DT Article ID HUMAN GENE-EXPRESSION; GENOME-WIDE ASSOCIATION; LONG-RANGE INTERACTION; GERMLINE EPIMUTATION; COLORECTAL-CANCER; ENHANCERS; VARIANTS; BREAST; TRAITS; MYC C1 [Mills, Ian G.] Univ Oslo, Nord European Mol Biol Lab EMBL Partnership, Norwegian Ctr Mol Med, Oslo, Norway. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freedman, Matthew L.] Eli & Edythe L Broad Inst MIT & Harvard, Cambridge, MA USA. [Monteiro, Alvaro N. A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Canc Epidemiol Program, Tampa, FL 33612 USA. [Gayther, Simon A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Gayther, Simon A.] UCL, Elizabeth Garrett Anderson Inst Womens Hlth EGA, Translat Res Lab, London, England. [Coetzee, Gerhard A.] Univ So Calif, Dept Urol, Norris Canc Ctr, Los Angeles, CA USA. [Risch, Angela; Plass, Christoph] German Canc Res Ctr, Div Epigenom & Canc Risk Factors, D-6900 Heidelberg, Germany. [Casey, Graham] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [De Biasi, Mariella] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Carlson, Chris] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Duggan, David] Translat Genom Res Inst TGen, Phoenix, AZ USA. [James, Michael; Liu, Pengyuan; Tichelaar, Jay W.; Vikis, Haris G.; You, Ming] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Mills, Ian G.] Canc Res UK Cambridge Res Inst, Urooncol Res Grp, Cambridge, England. RP Mills, IG (reprint author), Univ Oslo, Nord European Mol Biol Lab EMBL Partnership, Norwegian Ctr Mol Med, Oslo, Norway. EM ian.mills@ncmm.uio.no RI Plass, Christoph/H-7192-2014; Risch, Angela/H-2669-2013; OI Risch, Angela/0000-0002-8026-5505; Monteiro, Alvaro/0000-0002-8448-4801 FU NIH Post-Genome Wide Association Initiative [1U19CA148537-01, 1U19CA148065-01, 1U19CA148112-01, 1U19CA148107-01, 1U19CA148127-01] FX We would like to thank F. Bunz and all the members of the NIH Post-Genome Wide Association Initiative for helpful discussions and, in particular, I. Tomlinson (Wellcome Trust Centre for Human Genetics, Oxford). The contributing groups are supported by funding made available through the NIH Post-Genome Wide Association Initiative in response to Call (http://grants.nih.gov./grants/oer.htm). This Call sustains research across five cancer organ sites (prostate: 1U19CA148537-01; breast: 1U19CA148065-01; ovarian: 1U19CA148112-01; colorectal: 1U19CA148107-01; and lung: 1U19CA148127-01). For further information on this Initiative, please refer to the website: (http://epi.grants.cancer.gov/). In addition, this article is the product of the first attempt to engage the entire scientific community in the drafting of a scientific paper through open-access websites. We would like to thank R. Hoffmann at WikiGenes for hosting the pre-submission version of this submission (http://www.wikigenes.org/e/pub/e/84.html) and his unstinting energy and enthusiasm for this project and also Nature Precedings for hosting the same version (http://precedings.nature.com/documents/5162/version/1). NR 57 TC 182 Z9 187 U1 3 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JUN PY 2011 VL 43 IS 6 BP 513 EP 518 DI 10.1038/ng.840 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 769ME UT WOS:000291017000006 PM 21614091 ER PT J AU Yang, J Manolio, TA Pasquale, LR Boerwinkle, E Caporaso, N Cunningham, JM de Andrade, M Feenstra, B Feingold, E Hayes, MG Hill, WG Landi, MT Alonso, A Lettre, G Lin, P Ling, H Lowe, W Mathias, RA Melbye, M Pugh, E Cornelis, MC Weir, BS Goddard, ME Visscher, PM AF Yang, Jian Manolio, Teri A. Pasquale, Louis R. Boerwinkle, Eric Caporaso, Neil Cunningham, Julie M. de Andrade, Mariza Feenstra, Bjarke Feingold, Eleanor Hayes, M. Geoffrey Hill, William G. Landi, Maria Teresa Alonso, Alvaro Lettre, Guillaume Lin, Peng Ling, Hua Lowe, William Mathias, Rasika A. Melbye, Mads Pugh, Elizabeth Cornelis, Marilyn C. Weir, Bruce S. Goddard, Michael E. Visscher, Peter M. TI Genome partitioning of genetic variation for complex traits using common SNPs SO NATURE GENETICS LA English DT Article ID BODY-MASS INDEX; VON-WILLEBRAND-FACTOR; WIDE ASSOCIATION; HUMAN HEIGHT; LARGE PROPORTION; AGING RESEARCH; BLOOD-GROUP; FACTOR-VIII; HERITABILITY; POPULATION AB We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that similar to 45%, similar to 17%, similar to 25% and similar to 21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further similar to 0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein. C1 [Yang, Jian; Visscher, Peter M.] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia. [Manolio, Teri A.] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA. [Pasquale, Louis R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Div Epidemiol, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Caporaso, Neil; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Cunningham, Julie M.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [de Andrade, Mariza] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. [Feenstra, Bjarke; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Feingold, Eleanor] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Hayes, M. Geoffrey] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA. [Hill, William G.] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland. [Alonso, Alvaro] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Lettre, Guillaume] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Lin, Peng] Washington Univ, Sch Med, Human & Stat Genet Program, St Louis, MO USA. [Ling, Hua; Pugh, Elizabeth] Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA. [Mathias, Rasika A.] Johns Hopkins Univ, Sch Med, Dept Gen Internal Med, Baltimore, MD USA. [Cornelis, Marilyn C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Weir, Bruce S.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Goddard, Michael E.] Univ Melbourne, Dept Food & Agr Syst, Melbourne, Vic 3010, Australia. [Goddard, Michael E.] Dept Primary Ind, Biosci Res Div, Bundoora, Vic, Australia. RP Visscher, PM (reprint author), Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia. EM peter.visscher@qimr.edu.au RI Alonso, Alvaro/A-4917-2010; Hill, William/B-3198-2012; Weir, Bruce/A-2894-2013; Lin, P/G-7702-2014; Yang, Jian/A-5852-2010; OI Alonso, Alvaro/0000-0002-2225-8323; Yang, Jian/0000-0003-2001-2474; Feenstra, Bjarke/0000-0003-1478-649X; Goddard, Michael/0000-0001-9917-7946; Feingold, Eleanor/0000-0003-2898-6484; Visscher, Peter/0000-0002-2143-8760; de Andrade, Mariza/0000-0003-2329-2686 FU US National Institutes of Health Genes, Environment and Health Initiative; Research to Prevent Blindness in New York City; Canadian Institutes of Health Research; Australian National Health and Medical Research Council (NHMRC) [389892, 613672]; Australian Research Council (ARC) [DP0770096, DP1093900]; [U01 HG 004402]; [U01 HG 004399]; [U01 HG 004728]; [U01 HG04424]; [U01 HG 004446] FX Funding support for the Gene, Environment Association Studies (GENEVA) project has been provided through the US National Institutes of Health Genes, Environment and Health Initiative. For the ARIC project, support was from U01 HG 004402 (PI: E. A. Boerwinkle). For the NHS and HPFS support is from U01 HG 004399 and U01 HG 004728 (PIs: F. B. Hu and L. R. Pasquale). The genotyping for the ARIC, NHS and HPFS studies was performed at the Broad Institute of MIT and Harvard with funding support from U01 HG04424 (PI: S. Gabriel). The GENEVA Coordinating Center receives support from U01 HG 004446 (PI: B. S. Weir). Assistance with GENEVA data cleaning was provided by the National Center for Biotechnology Information. D. Crosslin and C. Laurie of the GENEVA project assisted in making the data available for analysis. A Physician Scientist Award from Research to Prevent Blindness in New York City also supports L. R. P. M. C. C. is a recipient of a Canadian Institutes of Health Research Fellowship. We acknowledge funding from the Australian National Health and Medical Research Council (NHMRC grants 389892 and 613672) and the Australian Research Council (ARC grants DP0770096 and DP1093900). We thank D. Posthuma for discussions and the referees for constructive comments. NR 43 TC 341 Z9 345 U1 9 U2 73 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 JUN PY 2011 VL 43 IS 6 BP 519 EP U44 DI 10.1038/ng.823 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 769ME UT WOS:000291017000007 PM 21552263 ER PT J AU Yu, HY Tardivo, L Tam, S Weiner, E Gebreab, F Fan, CY Svrzikapa, N Hirozane-Kishikawa, T Rietman, E Yang, XP Sahalie, J Salehi-Ashtiani, K Hao, T Cusick, ME Hill, DE Roth, FP Braun, P Vidal, M AF Yu, Haiyuan Tardivo, Leah Tam, Stanley Weiner, Evan Gebreab, Fana Fan, Changyu Svrzikapa, Nenad Hirozane-Kishikawa, Tomoko Rietman, Edward Yang, Xinping Sahalie, Julie Salehi-Ashtiani, Kourosh Hao, Tong Cusick, Michael E. Hill, David E. Roth, Frederick P. Braun, Pascal Vidal, Marc TI Next-generation sequencing to generate interactome datasets SO NATURE METHODS LA English DT Article ID OPEN READING FRAMES; PROTEIN INTERACTIONS; GENOME; NETWORK; SYSTEM; MAP AB Next-generation sequencing has not been applied to protein-protein interactome network mapping so far because the association between the members of each interacting pair would not be maintained in en masse sequencing. We describe a massively parallel interactome-mapping pipeline, Stitch-seq, that combines PCRCR stitching with next-generation sequencing and used it to generate a new human interactome dataset. Stitch-seq is applicable to various interaction assays and should help expand interactome network mapping. C1 [Yu, Haiyuan; Tardivo, Leah; Tam, Stanley; Weiner, Evan; Gebreab, Fana; Fan, Changyu; Svrzikapa, Nenad; Hirozane-Kishikawa, Tomoko; Rietman, Edward; Yang, Xinping; Sahalie, Julie; Salehi-Ashtiani, Kourosh; Hao, Tong; Cusick, Michael E.; Hill, David E.; Roth, Frederick P.; Braun, Pascal; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Ctr Canc Syst Biol CCSB, Boston, MA 02115 USA. [Yu, Haiyuan; Tardivo, Leah; Tam, Stanley; Weiner, Evan; Gebreab, Fana; Fan, Changyu; Svrzikapa, Nenad; Hirozane-Kishikawa, Tomoko; Rietman, Edward; Yang, Xinping; Sahalie, Julie; Salehi-Ashtiani, Kourosh; Hao, Tong; Cusick, Michael E.; Hill, David E.; Braun, Pascal; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Yu, Haiyuan] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY USA. [Yu, Haiyuan] Cornell Univ, Weill Inst Cell & Mol Biol, Ithaca, NY USA. [Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. RP Braun, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Ctr Canc Syst Biol CCSB, Boston, MA 02115 USA. EM pascal_braun@dfci.harvard.edu; marc_vidal@dfci.harvard.edu RI Hill, David/B-6617-2011; Roth, Frederick/H-6308-2011; Braun, Pascal/B-9669-2013; OI Salehi-Ashtiani, Kourosh/0000-0002-6521-5243; Braun, Pascal/0000-0003-2012-6746; Roth, Frederick/0000-0002-6628-649X FU US National Human Genome Research Institute of the National Institutes of Health [R01 HG001715, R21 HG004756]; Ellison Foundation; Canadian Institute for Advanced Research Fellowship and Canada Excellence Research Chair; Dana-Farber Cancer Institute Strategic Initiative in support of Center for Cancer Systems Biology; Fonds de la Recherche Scientifique (French Community of Belgium) FX We thank members of the Dana-Farber Cancer Institute Center for Cancer Systems Biology and the Roth Laboratory for helpful discussions, and members of the University of Pennsylvania DNA Sequencing Facility in the Department of Genetics for the 454 FLX sequencing. This work was funded in part by grants R01 HG001715 (to D. E. H., F. P. R. and M. V.) and R21 HG004756 (to F. P. R.) from the US National Human Genome Research Institute of the National Institutes of Health, a grant from the Ellison Foundation (to M. V.), a Canadian Institute for Advanced Research Fellowship and Canada Excellence Research Chair (to F. P. R.) and in part by Institute Sponsored Research funds from the Dana-Farber Cancer Institute Strategic Initiative in support of Center for Cancer Systems Biology. M. V. is supported as a Chercheur Qualifie Honoraire from the Fonds de la Recherche Scientifique (French Community of Belgium). NR 20 TC 86 Z9 87 U1 1 U2 18 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 JUN PY 2011 VL 8 IS 6 BP 478 EP U2257 DI 10.1038/NMETH.1597 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 769QB UT WOS:000291031800016 PM 21516116 ER PT J AU Makimura, H AF Makimura, Hideo TI OBESITY Cure obesity: sleep more, eat out less and turn down the heat? SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Editorial Material ID BROWN ADIPOSE-TISSUE AB Optimal strategies to treat patients with obesity have remained elusive. Now, Bo et al. demonstrate the contribution of a set of easily changeable lifestyle factors-sleep restriction, high consumption of restaurant meals and increased room temperature-to the incidence of obesity and hyperglycemia in an Italian population-based cohort. C1 [Makimura, Hideo] Harvard Univ, Sch Med, Program Nutr Metab, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Makimura, Hideo] Harvard Univ, Sch Med, Neuroendocrine Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Makimura, H (reprint author), Harvard Univ, Sch Med, Program Nutr Metab, Massachusetts Gen Hosp, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM hmakimura@partners.org FU NIDDK NIH HHS [K23 DK087857] NR 10 TC 2 Z9 2 U1 1 U2 4 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 JUN PY 2011 VL 7 IS 6 BP 318 EP 319 DI 10.1038/nrendo.2011.55 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 769JH UT WOS:000291008200002 PM 21448142 ER PT J AU Cheung, OS Richler, JJ Phillips, WS Gauthier, I AF Cheung, Olivia S. Richler, Jennifer J. Phillips, W. Stewart Gauthier, Isabel TI Does temporal integration of face parts reflect holistic processing? SO PSYCHONOMIC BULLETIN & REVIEW LA English DT Article DE Oscillator strength; face perception; holistic perception; response conflict; composite paradigm, temporal information processing ID TIME-COURSE ANALYSIS; RECOGNITION; PERCEPTION; INTERFERENCE AB We examined whether temporal integration of face parts reflects holistic processing or response interference. Participants learned to name two faces "Fred" and two "Bob." At test, the top and bottom halves of different faces formed composites and were presented briefly separated in time. Replicating prior findings (Singer & Sheinberg, Vision Research, 46, 1838-1847, 2006), naming of the target half for aligned composites was slowed when the irrelevant half was from a face with a different name rather than from the original face. However, no interference was observed when the irrelevant half had a name identical to the name of the target half but came from a different learned face, arguing against a true holistic effect. Instead, response interference was obtained when the target half briefly preceded the irrelevant half. Experiment 2 confirmed a double dissociation of holistic processing versus response interference for intact faces versus temporally separated face halves, suggesting that simultaneous presentation of facial information is critical for holistic processing. C1 [Cheung, Olivia S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. [Cheung, Olivia S.; Richler, Jennifer J.; Phillips, W. Stewart; Gauthier, Isabel] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. RP Cheung, OS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM olivia@nmr.mgh.harvard.edu OI Gauthier, Isabel/0000-0002-6249-4769 FU NEI NIH HHS [P30-EY008126, R01 EY013441, R01 EY013441-06A2, P30 EY008126] NR 19 TC 7 Z9 7 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1069-9384 J9 PSYCHON B REV JI Psychon. Bull. Rev. PD JUN PY 2011 VL 18 IS 3 BP 476 EP 483 DI 10.3758/s13423-011-0051-7 PG 8 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA 766TP UT WOS:000290809700004 PM 21327378 ER PT J AU Googe, J Brucker, AJ Bressler, NM Qin, HJ Aiello, LP Antoszyk, A Beck, RW Bressler, SB Ferris, FL Glassman, AR Marcus, D Stockdale, CR AF Googe, Joseph Brucker, Alexander J. Bressler, Neil M. Qin, Haijing Aiello, Lloyd P. Antoszyk, Andrew Beck, Roy W. Bressler, Susan B. Ferris, Frederick L., III Glassman, Adam R. Marcus, Dennis Stockdale, Cynthia R. CA Diabetic Retinopathy Writing Comm TI RANDOMIZEDTRIAL EVALUATING SHORT-TERM EFFECTS OF INTRAVITREAL RANIBIZUMAB OR TRIAMCINOLONE ACETONIDE ON MACULAR EDEMA AFTER FOCAL/GRID LASER FOR DIABETIC MACULAR EDEMA IN EYES ALSO RECEIVING PANRETINAL PHOTOCOAGULATION SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE proliferative diabetic retinopathy; diabetic macular edema; panretinal photocoagulation; ranibizumab; triamcinolone; randomized clinical trial; Diabetic Retinopathy Clinical Research Network ID ENDOTHELIAL GROWTH-FACTOR; CLINICAL-TRIAL; RETINOPATHY AB Purpose: To evaluate 14-week effects of intravitreal ranibizumab or triamcinolone in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation. Methods: Three hundred and forty-five eyes with a visual acuity of 20/320 or better, center-involved diabetic macular edema receiving focal/grid laser, and diabetic retinopathy receiving prompt panretinal photocoagulation were randomly assigned to sham (n = 123), 0.5-mg ranibizumab (n = 113) at baseline and 4 weeks, and 4-mg triamcinolone at baseline and sham at 4 weeks (n = 109). Treatment was at investigator discretion from 14 weeks to 56 weeks. Results: Mean changes (+/-SD) in visual acuity letter score from baseline were significantly better in the ranibizumab (+1 +/- 11; P < 0.001) and triamcinolone (+2 +/- 11; P, 0.001) groups compared with those in the sham group (24 +/- 14) at the 14-week visit, mirroring retinal thickening results. These differences were not maintained when study participants were followed for 56 weeks for safety outcomes. One eye (0.9%; 95% confidence interval, 0.02%-4.7%) developed endophthalmitis after receiving ranibizumab. Cerebrovascular/cardiovascular events occurred in 4%, 7%, and 3% of the sham, ranibizumab, and triamcinolone groups, respectively. Conclusion: The addition of 1 intravitreal triamcinolone injection or 2 intravitreal ranibizumab injections in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation is associated with better visual acuity and decreased macular edema by 14 weeks. Whether continued long-term intravitreal treatment is beneficial cannot be determined from this study. RETINA 31: 1009-1027, 2011 C1 [Googe, Joseph; Diabetic Retinopathy] SE Retina Associates PC, Knoxville, TN USA. [Brucker, Alexander J.] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. [Bressler, Neil M.; Bressler, Susan B.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Qin, Haijing; Beck, Roy W.; Glassman, Adam R.; Stockdale, Cynthia R.] Jaeb Ctr Hlth Res, Tampa, FL USA. [Aiello, Lloyd P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. [Antoszyk, Andrew] Charlotte Eye Ear Nose & Throat Assoc PA, Charlotte, NC USA. [Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA. [Marcus, Dennis] SE Retina Ctr PC, Augusta, GA USA. RP Googe, J (reprint author), SE Retina Associates PC, Knoxville, TN USA. FU National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Department of Health and Human Services [EY14231, EY14229, EY018817]; Genentech; Allergan, Inc; Office of Research Administration; Allergan; Bausch Lomb; Carl Zeiss Meditec; EMMES Corporation; Lumenis; Notal Vision; Novartis; QLT; Regeneron; Steba Biotech; Abbott Medical Optics; ForSight Labs, LLC; Genzyme Corporation FX A complete list of the DRCR. net can be found at www.drcr.net. Supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and Department of Health and Human Services (EY14231, EY14229, and EY018817).; Genentech provided ranibizumab for the study, and Allergan, Inc, provided triamcinolone for the study. In addition, Genentech and Allergan, Inc, provided funds to DRCR. net to defray the study's clinical site costs.; A. J. Brucker: Genentech (C, G); L. P. Aiello: Genentech (O); A. Antoszyk: Genentech (C, G) and Allergan (G); S. S. Bressler: Genentech (G) and Allergan (G); D. Marcus: Genentech (C, G, T, B); N. Bressler: Grants to investigator at the Johns Hopkins University are negotiated and administered by the institution (such as the School of Medicine) that receives the grants, typically through the Office of Research Administration.; Dr. Neil Bressler is the principal investigator of grants at the Johns Hopkins University sponsored by the following entities (not including the National Institutes of Health): Allergan, Bausch & Lomb, Carl Zeiss Meditec, EMMES Corporation, Genentech, Lumenis, Notal Vision, Novartis, QLT, Regeneron, Steba Biotech, Abbott Medical Optics, ForSight Labs, LLC, and Genzyme Corporation. NR 28 TC 48 Z9 51 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 JUN PY 2011 VL 31 IS 6 BP 1009 EP 1027 DI 10.1097/IAE.0b013e318217d739 PG 19 WC Ophthalmology SC Ophthalmology GA 769JT UT WOS:000291009400002 ER PT J AU Sheetz, MJ Aiello, LP Shahri, N Davis, MD Kles, KA Danis, RP AF Sheetz, Matthew J. Aiello, Lloyd Paul Shahri, Nazila Davis, Matthew D. Kles, Keri A. Danis, Ronald P. CA Mbdv Study Grp TI EFFECT OF RUBOXISTAURIN (RBX) ON VISUAL ACUITY DECLINE OVER A 6-YEAR PERIOD WITH CESSATION AND REINSTITUTION OF THERAPY Results of an Open-Label Extension of the Protein Kinase C Diabetic Retinopathy Study 2 (PKC-DRS2) SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE ruboxistaurin; sustained moderate visual loss; open-label extension; diabetes; diabetic retinopathy ID PKC-BETA; COMPLICATIONS; GROWTH; NEOVASCULARIZATION; INHIBITION; ACTIVATION; MELLITUS; ISOFORMS AB Purpose: The PKC-DRS2 was a Phase 3, randomized, double-masked, placebo (PBO)controlled, 3-year study of the effect of 32 mg/day of ruboxistaurin (RBX), an orally administered protein kinase C inhibitor, on vision loss in patients with moderate to severe nonproliferative diabetic retinopathy. Ruboxistaurin reduced the occurrence of sustained moderate visual loss (SMVL; >15-letter decline in visual acuity sustained for the last 6 months of study participation) from 9.1% in the PBO group (N = 340) to 5.5% in the RBX group (N = 345, P = 0.034). This study evaluates the primary end point of SMVL in a 2-year open-label extension (OLE) of the PKC-DRS2, which began a median of 466 days (range, 263-1,296 days) after the conclusion of PKC-DRS2. Methods: Visual acuity was measured by certified examiners using the Early Treatment Diabetic Retinopathy Study chart. Results: Of the 514 patients who completed PKC-DRS2, 366 did so in the 32 study centers participating in the OLE, and of these, 203 (55%) enrolled in the OLE for treatment with 32 mg/day of RBX for 2 years. Of the 203 enrolled in the OLE, 100 had previously been treated with PBO (prior PBO subgroup) and 103 had been treated with RBX (prior RBX subgroup). PKC-DRS2 baseline patient and ocular characteristics were well matched between these two subgroups and were similar to the PKC-DRS2 patient population as a whole. Using the PKC-DRS2 baseline as the starting point, SMVL occurred in 6% of the prior PBO subgroup during the PKC-DRS2, increasing to 26% by the end of the OLE. However, in the prior RBX subgroup, SMVL occurred in only 4% and 8% during the PKC-DRS2 and by the end of the OLE, respectively (P < 0.001 for difference at the end of the OLE). In the prior PBO subgroup, mean visual acuity declined from 79.6 letters at PKC-DRS2 baseline to 73.1 letters at OLE end point (26.5 letters). In the prior RBX subgroup, this loss was 2.7 letters (79.8 to 77.1) over the same period (P = 0.02). Conclusion: Over a 6-year study period incorporating 3 years of a rigorously placebo-controlled trial, approximately 1 year off treatment and 2-year OLE where all groups received therapy, those patients with greatest RBX exposure (similar to 5 years) experienced less SMVL compared with those in the original PBO group (similar to 2-year RBX exposure). RETINA 31: 1053-1059, 2011 C1 [Sheetz, Matthew J.; Kles, Keri A.] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02115 USA. [Shahri, Nazila] I3 Statprobe, San Diego, CA USA. [Davis, Matthew D.; Danis, Ronald P.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. RP Sheetz, MJ (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM msheetz@lilly.com FU Eli Lilly and Company FX Supported by Eli Lilly and Company. NR 19 TC 14 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JUN PY 2011 VL 31 IS 6 BP 1053 EP 1059 DI 10.1097/IAE.0b013e3181fe545f PG 7 WC Ophthalmology SC Ophthalmology GA 769JT UT WOS:000291009400006 PM 21386766 ER PT J AU Budd, MA AF Budd, Maggi A. TI Sex & Disability: Politics, Identity and Access SO SEXUALITY AND DISABILITY LA English DT Book Review C1 [Budd, Maggi A.] Harvard Univ, Sch Med, VA Boston Healthcare, Brockton, MA 02301 USA. RP Budd, MA (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare, 940 Belmont St, Brockton, MA 02301 USA. EM Margaret.budd@va.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD JUN PY 2011 VL 29 IS 2 BP 187 EP 189 DI 10.1007/s11195-011-9214-8 PG 3 WC Rehabilitation SC Rehabilitation GA 763QJ UT WOS:000290574500012 ER PT J AU Dosa, E Tuladhar, S Muldoon, LL Hamilton, BE Rooney, WD Neuwelt, EA AF Dosa, Edit Tuladhar, Suchita Muldoon, Leslie L. Hamilton, Bronwyn E. Rooney, William D. Neuwelt, Edward A. TI MRI Using Ferumoxytol Improves the Visualization of Central Nervous System Vascular Malformations SO STROKE LA English DT Article DE central nervous system; ferumoxytol; magnetic resonance imaging; ultrasmall superparamagnetic iron oxide nanoparticles; vascular malformations ID IRON-OXIDE; CONTRAST AGENT; PARTICLES; VENOGRAPHY; MECHANISMS; BRAIN AB Background and Purpose-Central nervous system vascular malformations (VMs) result from abnormal vasculo-and/or angiogenesis. Cavernomas and arteriovenous malformations are also sites of active inflammation. The aim of this study was to determine whether MRI detection of VMs can be improved by administration of ferumoxytol iron oxide nanoparticle, which acts as a blood pool agent at early time points and an inflammatory marker when taken up by tissue macrophages. Methods-Nineteen patients (11 men, 8 women; mean age, 47.5 years) with central nervous system VMs underwent 3-T MRI both with gadoteridol and ferumoxytol. The ferumoxytol-induced signal changes on the T1-, T2-, and susceptibility-weighted images were analyzed at 25 minutes (range, 21 to 30 minutes) and 24 hours (range, 22 to 27 hours). Results-Thirty-five lesions (capillary telangiectasia, n = 6; cavernoma, n = 21; developmental venous anomaly, n = 7; arteriovenous malformation, n = 1) were seen on the pre- and postgadoteridol images. The postferumoxytol susceptibility-weighted sequences revealed 5 additional VMs (3 capillary telangiectasias, 2 cavernomas) and demonstrated further tributary veins in all patients with developmental venous anomalies. The 24-hour T1 and T2 ferumoxytol-related signal abnormalities were inconsistent among patients and within VM types. No additional area of T1 or T2 enhancement was noted with ferumoxytol compared with gadoteridol in any lesion. Conclusions-Our findings indicate that the blood pool agent ferumoxytol provides important information about the number and true extent of VMs on the susceptibility-weighted MRI. The use of ferumoxytol as a macrophage imaging agent in the visualization of inflammatory cells within and around the lesions warrants further investigation. (Stroke. 2011;42:1581-1588.) C1 [Dosa, Edit; Tuladhar, Suchita; Muldoon, Leslie L.; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Hamilton, Bronwyn E.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97239 USA. [Rooney, William D.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97239 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,L603, Portland, OR 97239 USA. EM neuwelte@ohsu.edu FU National Institutes of Health, National Cancer Institute [CA137488]; National Institute of Neurological Disorders and Stroke [NS53468]; American Recovery and Reinvestment Ac [CA137488-15S1]; National Cancer Institute-Fredrick Cancer Research and Development Center; AMAG FX This work was supported by National Institutes of Health grants National Cancer Institute CA137488, National Institute of Neurological Disorders and Stroke NS53468, American Recovery and Reinvestment Act CA137488-15S1, and an National Cancer Institute-Fredrick Cancer Research and Development Center Contract to E.A.N.; AMAG Pharmaceuticals, Inc provided the study drug ferumoxytol free of charge. Oregon Health and Science University has received a sponsored research agreement from AMAG to conduct clinical trials of MRI with ferumoxytol. None of the authors has financial interest in this agent or in its developer, AMAG. NR 20 TC 27 Z9 28 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2011 VL 42 IS 6 BP 1581 EP 1588 DI 10.1161/STROKEAHA.110.607994 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 769QH UT WOS:000291032700034 PM 21493906 ER PT J AU Furie, KL AF Furie, Karen L. TI Response to Letter by Naylor Regarding Article, "Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association" SO STROKE LA English DT Letter C1 Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler MGH Stroke Res Ctr, Boston, MA 02114 USA. RP Furie, KL (reprint author), Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler MGH Stroke Res Ctr, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2011 VL 42 IS 6 BP E386 EP E386 DI 10.1161/STROKEAHA.111.614933 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 769QH UT WOS:000291032700003 ER PT J AU Krieger, JN Dobrindt, U Riley, DE Oswald, E AF Krieger, John N. Dobrindt, Ulrich Riley, Donald E. Oswald, Eric TI Acute Escherichia coli Prostatitis in Previously Health Young Men: Bacterial Virulence Factors, Antimicrobial Resistance, and Clinical Outcomes SO UROLOGY LA English DT Article ID URINARY-TRACT-INFECTION; MOLECULAR EPIDEMIOLOGY; PHYLOGENETIC GROUP; STRAINS; PYELONEPHRITIS; COMMENSALISM; GENOTYPES; ADHESINS; CYSTITIS; ISLAND AB OBJECTIVES To investigate clinical outomes, bacterial virulence factors, and antimicrobial resistance in E. coli from young men presenting with acute bacterial prostatitis. METHODS Initial E. coli isolates from previously healthy young men with no factors compromising urinary tract anatomy or function were tested for virulence-associated genes by polymerase chain reaction (PCR) assays, phylogenetic grouping by triplex polymerase PCR, and antibiotic resistance. RESULTS All 18 patients responded to treatment, including 2 who required long-term therapy. E. coli were allocated to phylogenetic groups B2 (13 strains) and D (5 strains). Prostatitis isolates belonged to clones mainly represented by extraintestinal pathogenic E. coli (ExPEC) and preferentially uropathogenic E. coli and displayed marked accumulation of virulence genes (hly, cdt1, clb, pap, sfa/foc, fyuA, iroN, kpsMT(II), and traT) characteristic of highly virulent ExPEC. All phylogenetic group B2 strains coded for at least 1 toxin with carcinogenic potential (Colibactin, cytolethal distending toxins, or cytotoxic necrotizing factor). In contrast to their accumulation of virulence-associated traits, prostatitis strains were sensitive to standard antibiotics. CONCLUSIONS The phylogenetic background and accumulation of an exceptional repertoire of extraintestinal pathogenic virulence-associated genes indicate that these E. coli strains belong to a highly virulent subset of uropathogenic variants. In contrast, antibiotic resistance was minimal in these E. coli strains from previously healthy, young outpatients. UROLOGY 77: 1420-1425, 2011. Published by Elsevier Inc. C1 [Krieger, John N.] Univ Washington, Sch Med, Dept Urol Surg, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Munster, Inst Hyg, Munster, Germany. CHU Toulouse, Lab Bacteriol Hyg, Toulouse, France. Univ Toulouse, Fac Med Purpan, Toulouse, France. RP Krieger, JN (reprint author), Univ Washington, Sch Med, Dept Urol Surg, VA Puget Sound Hlth Care Syst, UW Campus Mail Box 358280, Seattle, WA 98108 USA. EM jkrieger@uw.edu FU ERA-NET project; German Research Foundation [DO 789/4-1] FX This study was supported in part by the ERA-NET project, "Deciphering the intersection of extraintestinal pathogenic and commensal Escherichia coli." The authors would like to thank Michele Boury (Toulouse) and Barbara Plaschke (Wurzburg) for their excellent technical support. D was supported by the German Research Foundation (DO 789/4-1). NR 30 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUN PY 2011 VL 77 IS 6 BP 1420 EP 1425 DI 10.1016/j.urology.2010.12.059 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 769VX UT WOS:000291047500049 PM 21459419 ER PT J AU Durazzo, TC Tosun, D Buckley, S Gazdzinski, S Mon, A Fryer, SL Meyerhoff, DJ AF Durazzo, Timothy C. Tosun, Duygu Buckley, Shannon Gazdzinski, Stefan Mon, Anderson Fryer, Susanna L. Meyerhoff, Dieter J. TI Cortical Thickness, Surface Area, and Volume of the Brain Reward System in Alcohol Dependence: Relationships to Relapse and Extended Abstinence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Dependence; Neuroimaging; Brain Volume; Cortical Thickness; Surface Area; Relapse ID MAGNETIC-RESONANCE SPECTROSCOPY; CONSUMPTION FOLLOWING TREATMENT; NATIONAL EPIDEMIOLOGIC SURVEY; SUBSTANCE USE DISORDERS; HUMAN CEREBRAL-CORTEX; ADDICTED HUMAN BRAIN; DSM-IV ALCOHOL; ORBITOFRONTAL CORTEX; UNITED-STATES; DRUG-USE AB Background: At least 60% of those treated for an alcohol use disorder will relapse. Empirical study of the integrity of the brain reward system (BRS) is critical to understanding the mechanisms of relapse as this collection of circuits is implicated in the development and maintenance of all forms of addictive disorders. This study compared thickness, surface area, and volume in neocortical components of the BRS among nonsmoking light-drinking controls (controls), individuals who remained abstinent and those who relapsed after treatment. Methods: Seventy-five treatment-seeking alcohol-dependent individuals (abstinent for 7 +/- 3 days) and 43 controls completed 1.5T proton magnetic resonance imaging studies. Parcellated morphological data were obtained for following bilateral components of the BRS: rostral and caudal anterior cingulate cortex, insula, medial and lateral orbitofrontal cortex (OFC), rostral and caudal middle and superior frontal gyri, amygdala and hippocampus as well as for 26 other bilateral neocortical regions. Alcohol-dependent participants were followed over 12-months after baseline study and were classified as abstainers (no alcohol consumption; n = 24) and relapsers (any alcohol consumption; n = 51) at follow-up. Results: Relapsers and abstainers demonstrated lower cortical thickness in the vast majority of BRS regions as well as lower global thickness compared to controls. Relapsers had lower total BRS surface area than both controls and abstainers, but abstainers were not significantly different from controls on any surface area measure. Relapsers demonstrated lower volumes than controls in the majority of regions, while abstainers showed lower volumes than controls in the superior frontal gyrus, insula, amygdala, and hippocampus, bilaterally. Relapsers exhibited smaller volumes than abstainers in the right rostral middle and caudal middle frontal gyri and the lateral OFC, bilaterally. In relapsers, lower baseline volumes and surface areas in multiple regions were associated with a greater magnitude of post-treatment alcohol consumption. Conclusions: Results suggest relapsers demonstrated morphological abnormalities in regions involved in the "top down" regulation/modulation of internal drive states, emotions, reward processing, and behavior, which may impart increased risk for the relapse/remit cycle that afflicts many with an alcohol use disorder. Results also highlight the importance of examining both cortical thickness and surface area to better understand the nature of regional volume loss frequently observed in alcohol use disorders. Results from this report are consistent with previous research implicating plastic neurobiological changes in the BRS in the maintenance of addictive disorders. C1 [Durazzo, Timothy C.; Mon, Anderson; Fryer, Susanna L.; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Durazzo, Timothy C.; Tosun, Duygu; Buckley, Shannon; Gazdzinski, Stefan; Mon, Anderson; Fryer, Susanna L.; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. RP Durazzo, TC (reprint author), San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St,114M, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU National Institutes of Health [AA10788, DA24136] FX This material is the result of work supported by National Institutes of Health (AA10788 to D.J.M. and DA24136 to T.C.D.) and with resources and the use of facilities at the San Francisco Veterans Administration Medical Center, San Francisco CA. We thank Mary Rebecca Young, Bill Clift, Jeanne Eichenbaum and Drs. Peter Banys and Ellen Herbst of the Veterans Administration Substance Abuse Day Hospital and Dr. David Pating, Karen Moise and their colleagues at the Kaiser Permanente Chemical Dependency Recovery Program in San Francisco for their valuable assistance in recruiting participants. We also extend our gratitude to the study participants, who made this research possible. NR 93 TC 77 Z9 77 U1 2 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 BP 1187 EP 1200 DI 10.1111/j.1530-0277.2011.01452.x PG 14 WC Substance Abuse SC Substance Abuse GA 765FG UT WOS:000290688200021 PM 21410483 ER PT J AU Tschanz, JT Corcoran, CD Schwartz, S Treiber, K Green, RC Norton, MC Mielke, MM Piercy, K Steinberg, M Rabins, PV Leoutsakos, JM Welsh-Bohmer, KA Breitner, JCS Lyketsos, CG AF Tschanz, JoAnn T. Corcoran, Chris D. Schwartz, Sarah Treiber, Katherine Green, Robert C. Norton, Maria C. Mielke, Michelle M. Piercy, Kathleen Steinberg, Martin Rabins, Peter V. Leoutsakos, Jeanne-Marie Welsh-Bohmer, Kathleen A. Breitner, John C. S. Lyketsos, Constantine G. TI Progression of Cognitive, Functional, and Neuropsychiatric Symptom Domains in a Population Cohort With Alzheimer Dementia: The Cache County Dementia Progression Study SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Alzheimer disease; Alzheimer dementia; cognition; decline; dementia; neuropsychiatric symptoms; progression ID MINI-MENTAL-STATE; VASCULAR FACTORS; DISEASE; DECLINE; PROGNOSIS; AD; PREDICTORS; EPSILON-4; EDUCATION; SEVERITY AB Objectives: Progression of Alzheimer dementia (AD) is highly variable. Most estimates derive from convenience samples from dementia clinics or research centers where there is substantial potential for survival bias and other distortions. In a population-based sample of incident AD cases, we examined progression of impairment in cognition, function, and neuropsychiatric symptoms, and the influence of selected variables on these domains. Design: Longitudinal, prospective cohort study. Setting: Cache County (Utah). Participants: Three hundred twenty-eight persons with a diagnosis of possible/probable AD. Measurements: Mini-Mental State Exam (MMSE), Clinical Dementia Rating sum-of-boxes (CDR-sb), and Neuropsychiatric Inventory (NPI). Results: Over a mean follow-up of 3.80 (range: 0.07-12.90) years, the mean (SD) annual rates of change were -1.53 (2.69) scale points on the MMSE, 1.44 (1.82) on the CDR-sb, and 2.55 (5.37) on the NPI. Among surviving participants, 30% to 58% progressed less than 1 point per year on these measures, even 5 to 7 years after dementia onset. Rates of change were correlated between MMSE and CDR-sb (r = -0.62, df = 201, p < 0.001) and between the CDR-sb and NPI (r = 0.20, df = 206, p < 0.004). Female subjects (LR chi(2) = 8.7, df = 2, p = 0.013) and those with younger onset (likelihood ratio [LR] chi(2) = 5.7, df = 2, p = 0.058) declined faster on the MMSE. Although one or more apolipoprotein E epsilon 4 alleles and ever use of FDA-approved antidementia medications were associated with initial MMSE scores, neither was related to the rate of progression in any domain. Conclusions: A significant proportion of persons with AD progresses slowly. The results underscore differences between population-based versus clinic-based samples and suggest ongoing need to identify factors that may slow the progression of AD. (Am J Geriatr Psychiatry 2011; 19:532-542) C1 [Tschanz, JoAnn T.; Corcoran, Chris D.; Schwartz, Sarah; Norton, Maria C.; Piercy, Kathleen] Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. [Tschanz, JoAnn T.; Treiber, Katherine; Norton, Maria C.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Corcoran, Chris D.] Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. [Norton, Maria C.; Piercy, Kathleen] Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Med Genet, Boston, MA 02215 USA. [Mielke, Michelle M.; Steinberg, Martin; Rabins, Peter V.; Leoutsakos, Jeanne-Marie; Lyketsos, Constantine G.] Johns Hopkins Univ, Dept Psychiat, Johns Hopkins Bayview & Sch Med, Baltimore, MD USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC USA. [Breitner, John C. S.] Univ Washington, Sch Med, Seattle, WA USA. [Breitner, John C. S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Tschanz, JT (reprint author), Utah State Univ, Ctr Epidemiol Studies, 4440 Old Main Hill, Logan, UT 84322 USA. EM joann.tschanz@usu.edu RI Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Schwartz, Sarah/E-2050-2016; OI Schwartz, Sarah/0000-0001-9980-7493; Steinberg, Martin/0000-0001-8800-8020 FU NIH [R01AG-21136, R01AG11380, R01AG18712, R01HG02213, P30AG028377, K24AG027841, P30AG13846, NIA AG11380, NIA AG028377]; DPS; NIMH; NIA; Associated Jewish Federation of Baltimore; Weinberg Foundation; Forest; Glaxo-Smith-Kline; Eisai; Pfizer; Astra-Zeneca; Lilly; Ortho-McNeil; Bristol-Myers; Novartis FX This study is supported by NIH grants: R01AG-21136, R01AG11380, R01AG18712, R01HG02213, P30AG028377, K24AG027841, and P30AG13846.; The authors thank Dr Ronald Munger for his unqualified support of the DPS. They also thank the following individuals whose activities have helped to ensure the success of the project: Cara Brewer, B. A., Tony Calvert, B. A., R.N., Michelle Carlson, Ph.D., Elizabeth Fauth, Ph.D., Kimberly Graham, B. A., Kyle Hess, M. S., Hochang Ben Lee, M. D., Carol Leslie, M. S., Lawrence S. Mayer, Ph.D., Chiadi U. Onyike, M. D., Roxane Pfister, M. S., Georgiann Sanborn, M. S., Nancy Sassano, Ph.D., Ingmar Skoog, M. D., Heidi Wengreen, Ph. D., RD, James Wyatt, and Peter P. Zandi, Ph. D., M. P. H. Finally, they thank the participants and their families for their participation and support.; Authors disclosure: Peter V. Rabins: Legal testimony for Janssen Pharmaceutical; Martin Steinberg: Grant support from NIA and Elan Pharmaceuticals; Kathleen A. Welsh-Bohmer: 1) Scientific advisory board for Medivation, Inc. 2) Received funding for travel and speaker honoraria from Medivation, Inc., and Elan Corporation/Wyeth. 3) Has served/serves as an associate editor of Neuropsychology Review, on the editorial boards of Alzheimer's & Dementia, the Journal International Neuropsychological Society, and the Journal of Experimental and Clinical Neuropsychology, and as a consulting editor for Aging, Neuropsychology, and Cognition and Neuropsychology. 4) Holds US Patent #6867236 (issued 2005): Nonsteroidal Anti-inflammatory drugs for the treatment of Alzheimer's disease. 5) Receives royalties from the publication of Geriatric Neuropsychology: Assessment and Intervention (Guildford Publications, 2006). 6) Receives research support from the NIH (NIA AG11380 [PI] and NIA AG028377 [PI]); Constantine Lyketsos: 1) Grant support (research or CME)-NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, Glaxo-Smith-Kline, Eisai, Pfizer, Astra-Zeneca, Lilly, Ortho-McNeil, Bristol-Myers, Novartis. 2) Consultant/Advisor-Astra-Zeneca, Glaxo-Smith Kline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Genentech. 3) Honorarium or travel support-Pfizer, Forest, Glaxo-Smith Kline, Health Monitor; JoAnn Tschanz, Chris Corcoran, Sarah Schwartz, Katherine Treiber, Robert Green, Maria Norton, Michelle Mielke, Kathleen Piercy, Jeanne-Marie Leoutsakos, and John C. S. Breitner have no disclosures. NR 44 TC 59 Z9 61 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2011 VL 19 IS 6 BP 532 EP 542 DI 10.1097/JGP.0b013e3181faec23 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 766MP UT WOS:000290787300005 PM 21606896 ER PT J AU Givens, JL Prigerson, HG Kiely, DK Shaffer, ML Mitchell, SL AF Givens, Jane L. Prigerson, Holly G. Kiely, Dan K. Shaffer, Michele L. Mitchell, Susan L. TI Grief Among Family Members of Nursing Home Residents With Advanced Dementia SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Dementia; grief; nursing homes ID STAGE ALZHEIMERS-DISEASE; MENTAL-HEALTH; COMPLICATED GRIEF; TRAUMATIC GRIEF; BEREAVED CAREGIVERS; PHYSICAL MORBIDITY; OF-LIFE; DEATH; SYMPTOMS; CARE AB Objectives: To describe preloss and postloss grief symptoms among family members of nursing home (NH) residents with advanced dementia, and to identify predictors of greater postloss grief symptoms. Design: Prospective cohort study. Setting: 22 NHs in the greater Boston area. Participants: 123 family members of NH residents who died with advanced dementia. Measurements: Preloss grief was measured at baseline, and postloss grief was measured 2 and 7 months postloss using the Prolonged Grief Disorder Scale. Independent variables included resident and family member sociodemographic characteristics, resident comfort, acute illness, acute care prior to death, family member depression, and family member understanding of dementia and of resident's prognosis. Results: Levels of preloss and postloss grief were relatively stable from baseline to 7 months postloss. Feelings of separation and yearning were the most prominent grief symptoms. After multivariable adjustment, greater preloss grief and the family member having lived with the resident prior to NH admission were the only factors independently associated with greater postloss grief 7 months after resident death. Conclusions: The pattern of grieving for some family members of NH residents with advanced dementia is prolonged and begins before resident death. Identification of family members at risk for postloss grief during the preloss period may help guide interventions aimed at lessening postloss grief. (Am J Geriatr Psychiatry 2011; 19:543-550) C1 [Givens, Jane L.; Kiely, Dan K.; Mitchell, Susan L.] Hebrew SeniorLife Inst Aging Res, Boston, MA 02131 USA. [Givens, Jane L.; Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Prigerson, Holly G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shaffer, Michele L.] Penn State Coll Med, Hershey, PA USA. RP Givens, JL (reprint author), Hebrew SeniorLife Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM JaneGivens@hrca.harvard.edu FU NIH-NIA [R01 AG024091, K24AG033640]; Hartford Geriatrics Health Outcomes Research Scholars Award FX This work was supported by 1) NIH-NIA R01 AG024091, 2) Hartford Geriatrics Health Outcomes Research Scholars Award (JLG), and 3) NIH-NIA K24AG033640 (SLM). NR 36 TC 13 Z9 14 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2011 VL 19 IS 6 BP 543 EP 550 DI 10.1097/JGP.0b013e31820dcbe0 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 766MP UT WOS:000290787300006 PM 21606897 ER PT J AU Motyckova, G Murali, M AF Motyckova, Gabriela Murali, Mandakolathur TI Laboratory testing for cryoglobulins SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; MIXED CRYOGLOBULINEMIA; RITUXIMAB; EFFICACY; DISEASE; SAFETY AB Cryoglobulins are immunoglobulins that precipitate below 37 degrees C and can cause multiorgan damage. There are three types of cryoglobulins: Type I (also called simple), which is mostly associated with monoclonal gammopathy and/or other hematologic disorders and Type II and Type III (known as mixed cryoglobulins), which are associated with infectious and systemic diseases. Testing for cryoglobulins is complicated by lack of reference range, standards, and stringency in maintaining testing temperature conditions. Identification of cryoprecipitate can be critical for patient care; therefore, correct testing conditions are crucial for reliable cryoglobulin testing. The patient's blood sample should be kept at 37 degrees C initially to avoid premature precipitation of cryoglobulins and thereby decreasing the yield for subsequent identification. This could cause a false negative result. After warm centrifugation or warm cell precipitation, the clear serum is observed at 4 degrees C for formation of cryoprecipitate. The cryoprecipitate is then washed in cold buffer, and the resulting precipitate is warmed to 37 degrees C and subjected to further analysis by immunodiffusion and immunofixation. In addition to Meltzer's triad of purpura, weakness and arthralgias, cryoglobulinemias have protean manifestations involving skin, joints, kidney, nervous system, as well as the hematopoietic system. The management of cryoglobulinemia especially in patients with organ damage remains difficult. Treatment of cryoglobulinemia focuses on management of the underlying lymphoproliferative disorder or infectious or systemic causes. Medical management may also include corticosteroids and other immunosuppressive agents and plasmapheresis. Rituximab therapy seems to abrogate the aberrant B cell response. Am. J. Hematol. 86:500-502, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Murali, Mandakolathur] Massachusetts Gen Hosp, Clin Immunol Lab, Ctr Canc, Boston, MA 02114 USA. [Motyckova, Gabriela; Murali, Mandakolathur] Dana Farber Canc Inst, Boston, MA 02115 USA. [Murali, Mandakolathur] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Murali, M (reprint author), Massachusetts Gen Hosp, Clin Immunol Lab, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM mmurali@partners.org NR 17 TC 23 Z9 23 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2011 VL 86 IS 6 BP 500 EP 502 DI 10.1002/ajh.22023 PG 3 WC Hematology SC Hematology GA 766CI UT WOS:000290757400008 PM 21594887 ER PT J AU Sobota, A Neufeld, EJ Sprinz, P Heeney, MM AF Sobota, Amy Neufeld, Ellis J. Sprinz, Philippa Heeney, Matthew M. TI Transition from pediatric to adult care for sickle cell disease: Results of a survey of pediatric providers SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID HEALTH-CARE; CYSTIC-FIBROSIS; RISK-FACTORS; ADOLESCENTS; PERSPECTIVES; CHILDREN; SERVICES; PEOPLE AB As recently as the 1970s, children born with sickle cell disease (SCD) were unlikely to survive into adulthood. With advances in medical care, most patients now survive childhood and live into their forties or beyond [1,2]. A better transition from pediatric- to adult-focused care is therefore increasingly important [3]. Despite recent awareness of the importance of transition by the SCD community, little is known about existing transition programs. We conducted a survey of pediatric sickle cell clinics to describe current transition practices and identify areas for improvement. Survey topics included program demographics, transition logistics, assessment of patient transition readiness and independence, transition preparation, and program evaluation. Twenty-three clinics (77%) report having a transition program, although half have been in place for under 2 years. There is wide variation in specific transition practices. Most centers (97%) have an identified accepting adult provider, however, only 60% routinely transfer their patients to an adult hematologist specializing in SCD. Although there has been a recent effort to establish transition programs in pediatric sickle cell clinics, specific practices vary widely. As anticipated, lack of an accepting adult hematologist with an interest in SCD emerged as a common barrier to transition. C1 [Sobota, Amy; Sprinz, Philippa] Boston Med Ctr, Div Pediat Hematol Oncol, Boston, MA 02118 USA. [Sobota, Amy; Neufeld, Ellis J.; Heeney, Matthew M.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Sobota, Amy; Neufeld, Ellis J.; Heeney, Matthew M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sobota, Amy; Sprinz, Philippa] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Neufeld, Ellis J.; Heeney, Matthew M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Sobota, A (reprint author), Boston Med Ctr, Div Pediat Hematol Oncol, Yawkey Bldg 4S-11,850 Harrison Ave, Boston, MA 02118 USA. EM amy.sobota@bmc.org RI Neufeld, Ellis/F-9331-2011; Heeney, Matthew/J-6838-2015 OI Sobota, Amy/0000-0003-3979-7435; Heeney, Matthew/0000-0002-1104-6843 FU AHRQ HHS [T32 HS000063]; NHLBI NIH HHS [K24 HL004184] NR 27 TC 14 Z9 14 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2011 VL 86 IS 6 BP 512 EP 515 DI 10.1002/ajh.22016 PG 5 WC Hematology SC Hematology GA 766CI UT WOS:000290757400015 PM 21594889 ER PT J AU O'Seaghdha, CM Hwang, SJ Bhavsar, NA Kottgen, A Coresh, J Astor, BC Fox, CS AF O'Seaghdha, Conall M. Hwang, Shih-Jen Bhavsar, Nrupen A. Koettgen, Anna Coresh, Josef Astor, Brad C. Fox, Caroline S. TI Lower Urinary Connective Tissue Growth Factor Levels and Incident CKD Stage 3 in the General Population SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease; connective tissue growth factor; epidemiology ID CHRONIC KIDNEY-DISEASE; TGF-BETA; DIABETIC-NEPHROPATHY; TUBULOINTERSTITIAL FIBROSIS; ATHEROSCLEROSIS RISK; RENAL-INSUFFICIENCY; FACTOR EXCRETION; UNITED-STATES; EXPRESSION; PREVALENCE AB Background: Connective tissue growth factor (CTGF) is involved in the development and progression of kidney diseases, including diabetic nephropathy and kidney fibrosis, but also may have a role in mesangial repair after injury. It is unknown whether, in the general population, urinary CTGF levels are associated with a decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m(2) (ie, development of chronic kidney disease [CKD] stage 3). Study Design: Nested case-control. Setting & Participants: 100 cases of incident CKD stage 3 and 100 age-and sex-matched controls in the Framingham Heart Study; 141 cases and 135 age-, sex-, and race-matched controls in the Atherosclerosis Risk in Communities (ARIC) Study. Controls had eGFR >= 60 mL/min/1.73 m(2) at follow-up in both studies. Predictors: Urinary CTGF concentrations. Outcomes: Incident CKD stage 3, defined as eGFR <60 mL/min/1.73 m(2). Measurements: Stored urine samples from Framingham Heart Study and ARIC were measured for CTGF. Covariates were obtained from Framingham Heart Study and ARIC participant examinations. Results: In the Framingham Heart Study, the median baseline urinary CTGF concentration was lower in cases (1.35 ng/mL) than controls (2.35 ng/mL; paired t test, P < 0.0001). The multivariable-adjusted OR for incident CKD stage 3 was 0.33 (95% CI, 0.17-0.64; P < 0.001) per 1-standard deviation in log urinary CTGF level after adjustment for CKD risk factors, baseline eGFR, and baseline log urinary albumin-creatinine ratio, with similar results in participants without diabetes (n = 184). Results were not materially different when urinary CTGF level was indexed to urinary creatinine level (multivariable-adjusted OR, 0.34; 95% CI, 0.21-0.56; P < 0.001). A similar, but nonsignificant, trend of risk of incident CKD stage 3 with lower baseline urinary CTGF concentration was observed in an independent case-control study conducted in the ARIC Study, with the strongest results observed in participants free of diabetes. This inverse relationship was robust in meta-analysis of both the overall and diabetes-free groups. Limitations: Observational study; causality cannot be inferred. Conclusions: Lower urinary CTGF concentrations precede the onset of CKD stage 3 in the general population. Further work is required to fully characterize how CTGF level influences risk of CKD. Am J Kidney Dis. 57(6): 841-849. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham Heart Study, Framingham, MA 01702 USA. [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham Heart Study, Bethesda, MD 20892 USA. [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Bethesda, MD USA. [O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Div Renal, Boston, MA 02114 USA. [Bhavsar, Nrupen A.; Koettgen, Anna; Coresh, Josef; Astor, Brad C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Bhavsar, Nrupen A.; Coresh, Josef; Astor, Brad C.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Koettgen, Anna] Univ Hosp Freiburg, Div Renal, Freiburg, Germany. [Coresh, Josef; Astor, Brad C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. [Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [O'Seaghdha, Conall M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. RP Fox, CS (reprint author), NHLBI, Div Intramural Res, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI Kottgen, Anna/D-2920-2012 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022]; American Diabetes Association; National Institute of Diabetes and Digestive and Kidney Diseases [1 R01 DK076770-01]; [U01HL075572-01] FX The Framingham Heart Study is supported by grant N01-HC-25195 from the National Heart, Lung, and Blood Institute (NHLBI); Framingham Heart Study UACR measurements were supported by an American Diabetes Association Research Grant. ARIC sample assays were supported by the National Institute of Diabetes and Digestive and Kidney Diseases (1 R01 DK076770-01). ARIC is carried out as a collaborative study supported by NHLBI contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022, with the ARIC carotid MRI examination funded by U01HL075572-01. NR 53 TC 13 Z9 14 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUN PY 2011 VL 57 IS 6 BP 841 EP 849 DI 10.1053/j.ajkd.2010.11.022 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 766MX UT WOS:000290788400008 PM 21292366 ER PT J AU Howrigan, DP Laird, NM Smoller, JW Devlin, B McQueen, MB AF Howrigan, D. P. Laird, N. M. Smoller, J. W. Devlin, B. McQueen, M. B. TI Using Linkage Information to Weight a Genome-Wide Association of Bipolar Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE biploar disorder; genome-wide association; weighted false discovery approach ID SEROTONIN TRANSPORTER GENE; GIRDLE MUSCULAR-DYSTROPHY; FAMILY-BASED ASSOCIATION; MYOSIN VB; INCLUSION DISEASE; I DISORDER; POLYMORPHISMS; SUSCEPTIBILITY; METAANALYSIS; COMORBIDITY AB Issues of multiple-testing and statistical significance in genome-wide association studies (GWAS) have prompted statistical methods utilizing prior data to increase the power of association results. Using prior findings from genome-wide linkage studies on bipolar disorder (BPD), we employed a weighted false discovery approach (wFDR; [Roeder et al. 2006. Am J Hum Genet 78(2): 243-252]) to previously reported GWAS data drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Using this method, association signals are up or down-weighted given the linkage score in that genomic region. Although no SNPs in our sample reached genome-wide significance through the wFDR approach, the strongest single SNP result from the original GWAS results (rs4939921 in myosin VB) is strongly up-weighted as it occurs on a linkage peak of chromosome 18. We also identify regions on chromosome 9, 17, and 18 where modestly associated SNP clusters coincide with strong linkage scores, implicating them as possible candidate regions for further analysis. Moving forward, we believe the application of prior linkage information will be increasingly useful to future GWAS studies that incorporate rarer variants into their analysis. (C) 2011 Wiley-Liss, Inc. C1 [Howrigan, D. P.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Howrigan, D. P.; McQueen, M. B.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Laird, N. M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Smoller, J. W.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. [Devlin, B.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [McQueen, M. B.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. RP Howrigan, DP (reprint author), Univ Colorado, Dept Psychol, Campus Box 345, Boulder, CO 80309 USA. EM daniel.howrigan@gmail.com FU National Institute of Child Health and Human Development [T32 HD007289]; National Institute of Mental Health [T32 MH016880, MH063445]; National Institute on Drug Abuse [DA011015] FX Grant sponsor: National Institute of Child Health and Human Development; Grant Number: T32 HD007289; Grant sponsor: National Institute of Mental Health; Grant Number: T32MH016880; Grant sponsor: National Institute on Drug Abuse; Grant Number: DA011015; Grant sponsor: National Institute of Mental Health; Grant Number: MH063445. NR 39 TC 6 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUN PY 2011 VL 156B IS 4 BP 462 EP 471 DI 10.1002/ajmg.b.31183 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 766FA UT WOS:000290765200011 PM 21480485 ER PT J AU Samuels, J Wang, Y Riddle, MA Greenberg, BD Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Grados, MA Knowles, JA Piacentini, J Cullen, B Bienvenu, OJ Rasmussen, SA Geller, D Pauls, DL Liang, KY Shugart, YY Nestadt, G AF Samuels, Jack Wang, Ying Riddle, Mark A. Greenberg, Benjamin D. Fyer, Abby J. McCracken, James T. Rauch, Scott L. Murphy, Dennis L. Grados, Marco A. Knowles, James A. Piacentini, John Cullen, Bernadette Bienvenu, O. Joseph, III Rasmussen, Steven A. Geller, Daniel Pauls, David L. Liang, Kung-Yee Shugart, Yin Y. Nestadt, Gerald TI Comprehensive Family-Based Association Study of the Glutamate Transporter Gene SLC1A1 in Obsessive-Compulsive Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE obsessive-compulsive disorder; glutamate transporter; candidate gene ID OCD COLLABORATIVE GENETICS; O-METHYLTRANSFERASE COMT; LINKAGE ANALYSIS; SEX; SCHIZOPHRENIA; SUPPORTS; AUTISM; SAMPLE AB SLC1A1 encodes a neuronal glutamate transporter and is a promising candidate gene for obsessive-compulsive disorder (OCD). Several independent research groups have reported significant associations between OCD and single nucleotide polymorphisms (SNPs) in this gene. Previously, we evaluated 13 SNPs in, or near, SLC1A1 and reported a strong association signal with rs301443, a SNP 7.5 kb downstream of the gene [Shugart et al. (2009); Am J Med Genet Part B 150B:886-892]. Theaims of the current study were first, to further investigate this finding by saturating the region around rs301443; and second, to explore the entire gene more thoroughly with a dense panel of SNP markers. We genotyped an additional 111 SNPs in or near SLC1A1, covering from 9 kb upstream to 84 kb downstream of the gene at average spacing of 1.7 kb per SNP, and conducted family-based association analyses in 1,576 participants in 377 families. We found that none of the surrounding markers were in linkage disequilibrium with rs301443, nor were any associated with OCD. We also found that SNP rs4740788, located about 8.8 kb upstream of the gene, was associated with OCD in all families (P = 0.003) and in families with male affecteds (P = 0.002). A three-SNP haplotype (rs4740788-rs10491734-rs10491733) was associated with OCD in the total sample (P = 0.00015) and in families with male affecteds (P = 0.0007). Although of nominal statistical significance considering the number of comparisons, these findings provide further support for the involvement of SLC1A1 in the pathogenesis of OCD. (C) 2011 Wiley-Liss, Inc. C1 [Samuels, Jack; Wang, Ying; Riddle, Mark A.; Grados, Marco A.; Cullen, Bernadette; Bienvenu, O. Joseph, III; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21231 USA. [Greenberg, Benjamin D.; Rasmussen, Steven A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Fyer, Abby J.] Columbia Univ, New York State Psychiat Inst, Dept Psychiat, Coll Phys & Surg, New York, NY USA. [McCracken, James T.; Piacentini, John] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Rauch, Scott L.; Geller, Daniel] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Knowles, James A.] Univ So Calif, Sch Med, Dept Psychiat, Los Angeles, CA USA. [Pauls, David L.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Liang, Kung-Yee] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Shugart, Yin Y.] NIMH, Genom Res Branch, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA. RP Samuels, J (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 1629 Thames St,Suite 401, Baltimore, MD 21231 USA. EM jacks@jhmi.edu RI Liang, Kung-Yee/F-8299-2011; OI Samuels, Jack/0000-0002-6715-7905 FU National Institute of Mental Health [RO1MH50214, R01MH071507, NIH/NCRR/OPD-GCRC RR00052] FX Grant sponsor: National Institute of Mental Health; Grant numbers: RO1MH50214, R01MH071507, NIH/NCRR/OPD-GCRC RR00052. NR 40 TC 32 Z9 34 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUN PY 2011 VL 156B IS 4 BP 472 EP 477 DI 10.1002/ajmg.b.31184 PG 6 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 766FA UT WOS:000290765200012 PM 21445956 ER PT J AU Yu, EW Bauer, SR Bain, PA Bauer, DC AF Yu, Elaine W. Bauer, Scott R. Bain, Paul A. Bauer, Douglas C. TI Proton Pump Inhibitors and Risk of Fractures: A Meta-Analysis of 11 International Studies SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Bone mineral density; Calcium absorption; Fracture; H2-receptor antagonists; Osteoporosis; Proton pump inhibitor ID BONE-MINERAL DENSITY; HIP FRACTURE; CALCIUM-ABSORPTION; ACQUIRED PNEUMONIA; ACID SUPPRESSION; OLDER-ADULTS; K+-ATPASE; OMEPRAZOLE; WOMEN; THERAPY AB BACKGROUND: Concerns have been raised about the risk of fractures with acid-suppressive medications, such as proton pump inhibitors and histamine(2)-receptor antagonists. METHODS: This meta-analysis evaluated the association between proton pump inhibitor or histamine(2)-receptor antagonist use and fractures. We performed a systematic search of published literature (1970 to October 10, 2010) in MEDLINE, EMBASE, and other sources. Ten publications reporting 11 studies were considered eligible for analysis. RESULTS: All studies were observational case-control or cohort studies and primarily evaluated older adults. The summary effect estimate for risk of hip fracture increased modestly among individuals taking proton pump inhibitors (relative risk [RR] 1.30, 95% confidence interval [CI], 1.19-1.43). There also was an increase in spine (RR 1.56, 95% CI, 1.31-1.85) and any-site fractures (RR 1.16, 95% CI, 1.04-1.30) among proton pump inhibitor users. These findings were similar in both men and women and after stratification by duration of use. In contrast, histamine(2)-receptor antagonist use was not significantly associated with increased risk of hip fracture (RR 1.12, 95% CI, 0.97-1.30). CONCLUSION: In this meta-analysis of observational studies, proton pump inhibitors modestly increased the risk of hip, spine, and any-site fractures, whereas histamine(2)-receptor antagonists were not associated with fracture risk. The possibility of residual confounding cannot be excluded. Further skeletal evaluation should be considered for patients who are taking proton pump inhibitors and also at risk for osteoporotic fracture. (C) 2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, 519-526 C1 [Yu, Elaine W.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bauer, Scott R.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bain, Paul A.] Harvard Univ, Sch Med, Countway Lib Med, Boston, MA 02115 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA USA. RP Yu, EW (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 1051, Boston, MA 02114 USA. EM ewyu@partners.org FU National Institutes of Health [K24 ARO51895] FX Dr Bauer is supported by National Institutes of Health Grant K24 ARO51895. NR 45 TC 105 Z9 112 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 2011 VL 124 IS 6 BP 519 EP 526 DI 10.1016/j.amjmed.2011.01.007 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 768BD UT WOS:000290905400015 PM 21605729 ER PT J AU Tabatabaei, S Saylor, PJ Coen, J Dahl, DM AF Tabatabaei, Shahin Saylor, Philip J. Coen, John Dahl, Douglas M. TI Prostate Cancer Imaging: What Surgeons, Radiation Oncologists, and Medical Oncologists Want to Know SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE cancer staging; CT; MRI; prostate neoplasms; transrectal ultrasound ID BONE; METASTASES; CARCINOMA AB OBJECTIVE. The purpose of this article is to discuss the information that is important to note in imaging reports of patients with prostate cancer. CONCLUSION. Accurate staging through imaging is an integral part of prostate cancer management. Ultrasound, CT, bone scanning, and MRI are used for prostate cancer patients to assess the primary tumor, lymph node status, and bone metastasis. Accurate reporting of images is crucial for effective cancer treatment. C1 [Tabatabaei, Shahin; Dahl, Douglas M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Urol, Boston, MA 02114 USA. [Saylor, Philip J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Canc Ctr, Boston, MA 02114 USA. [Coen, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Tabatabaei, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM stabatabaei@partners.org NR 15 TC 8 Z9 8 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2011 VL 196 IS 6 BP 1263 EP 1266 DI 10.2214/AJR.10.6263 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767JX UT WOS:000290854000038 PM 21606287 ER PT J AU Eisner, BH McQuaid, JW Hyams, E Matlaga, BR AF Eisner, Brian H. McQuaid, Joseph W. Hyams, Elias Matlaga, Brian R. TI Nephrolithiasis: What Surgeons Need to Know SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE imaging; kidney; nephrolithiasis; ureter ID UNENHANCED HELICAL CT; SHOCK-WAVE LITHOTRIPSY; ACUTE FLANK PAIN; COMPUTED-TOMOGRAPHY; MULTIDETECTOR CT; URINARY CALCULI; STONE COMPOSITION; URETERAL CALCULI; RENAL-CALCULI; MR UROGRAPHY AB OBJECTIVE. In this article, we review the standard of care for imaging of nephrolithiasis as well as new technology and radiation concerns from the perspective of the urologic surgeon. CONCLUSION. Nephrolithiasis is a common cause of morbidity with a lifetime prevalence of 5-10% worldwide. Increasingly, diagnostic evaluation and planning for medical or surgical intervention have become reliant on imaging. C1 [Eisner, Brian H.; McQuaid, Joseph W.] Harvard Univ, Massachusetts Gen Hosp, Dept Urol, Kidney Stone Ctr,Med Sch, Boston, MA 02114 USA. [Hyams, Elias; Matlaga, Brian R.] Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Urol, Kidney Stone Ctr,Med Sch, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 60 TC 12 Z9 12 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2011 VL 196 IS 6 BP 1274 EP 1278 DI 10.2214/AJR.11.6434 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767JX UT WOS:000290854000040 PM 21606289 ER PT J AU Seaman, DM Meyer, CA Gilman, MD McCormack, FX AF Seaman, Danielle M. Meyer, Cristopher A. Gilman, Matthew D. McCormack, Francis X. TI Diffuse Cystic Lung Disease at High-Resolution CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE cystic lung disease; high-resolution CT; interstitial lung disease; Langerhans cell histiocytosis; lymphangioleiomyomatosis ID THIN-SECTION CT; LYMPHANGIOLEIOMYOMATOSIS; AMYLOIDOSIS; SARCOMA AB OBJECTIVE. This article will illustrate and describe the spectrum of diseases associated with air cysts at high-resolution CT (HRCT). CONCLUSION. HRCT is an important modality in the evaluation of interstitial lung disease to include cystic lung disease. Although most commonly associated with lymphangioleiomyomatosis or Langerhans cell histiocytosis, cystic lung disease is increasingly being recognized as a feature of other entities. Awareness of the spectrum of HRCT findings associated with these diseases may help the trained observer narrow the differential diagnosis. C1 [Seaman, Danielle M.] Duke Univ, Dept Radiol, Med Ctr, Durham, NC 27710 USA. [Meyer, Cristopher A.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. [Gilman, Matthew D.] Massachusetts Gen Hosp, Dept Radiol, Div Thorac Radiol, Boston, MA 02114 USA. [McCormack, Francis X.] Univ Cincinnati, Coll Med, Dept Internal Med, Div Pulm Crit Care & Sleep Med, Cincinnati, OH USA. RP Seaman, DM (reprint author), Duke Univ, Dept Radiol, Med Ctr, Box 3808 DUMC, Durham, NC 27710 USA. EM seaman.danielle@gmail.com OI McCormack, Francis/0000-0001-7168-9464 NR 16 TC 40 Z9 42 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2011 VL 196 IS 6 BP 1305 EP 1311 DI 10.2214/AJR.10.4420 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767JX UT WOS:000290854000044 PM 21606293 ER PT J AU Asrani, A Kaewlai, R Digumarthy, S Gilman, M Shepard, JAO AF Asrani, Ashwin Kaewlai, Rathachai Digumarthy, Subba Gilman, Matthew Shepard, Jo-Anne O. TI Urgent Findings on Portable Chest Radiography: What the Radiologist Should Know-Review SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE chest imaging; emergency radiology; hemothorax; lobar collapse; mediastinal hematoma; pneumomediastinum; pneumothorax; pulmonary edema; pulmonary embolism; pulmonary hemorrhage; pulmonary infarct ID ACUTE PULMONARY-EMBOLISM; THIN-SECTION CT; PNEUMOMEDIASTINUM; DIAGNOSIS; DISEASE; EDEMA; LUNG; SIGN; PNEUMOTHORAX; ANGIOGRAPHY C1 [Asrani, Ashwin] Weill Cornell Med Coll, Dept Radiol, New York, NY 10065 USA. [Kaewlai, Rathachai; Digumarthy, Subba; Gilman, Matthew; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Thorac Radiol, Boston, MA 02114 USA. RP Asrani, A (reprint author), Weill Cornell Med Coll, Dept Radiol, 525 E 68th St, New York, NY 10065 USA. EM ashwinasrani@yahoo.com OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 41 TC 1 Z9 1 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2011 VL 196 IS 6 SU S BP S45 EP S61 DI 10.2214/AJR.09.7170 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767JK UT WOS:000290852500001 PM 21606235 ER PT J AU Asrani, A Kaewlai, R Digumarthy, S Gilman, M Shepard, JA AF Asrani, Ashwin Kaewlai, Rathachai Digumarthy, Subba Gilman, Matthew Shepard, Jo-Anne TI Urgent Findings on Portable Chest Radiography: What the Radiologist Should Know-Self-Assessment Module SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chest imaging; emergency radiology; hemothorax; lobar collapse; mediastinal hematoma; pneumomediastinum; pneumothorax; pulmonary edema; pulmonary embolism; pulmonary hemorrhage; pulmonary infarct AB The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the spectrum of urgent findings on portable chest radiography. C1 [Asrani, Ashwin] Weill Cornell Med Coll, Dept Radiol, New York, NY 10065 USA. [Kaewlai, Rathachai; Digumarthy, Subba; Gilman, Matthew; Shepard, Jo-Anne] Massachusetts Gen Hosp, Dept Thorac Radiol, Boston, MA 02114 USA. RP Asrani, A (reprint author), Weill Cornell Med Coll, Dept Radiol, 525 E 68th St, New York, NY 10065 USA. EM ashwinasrani@yahoo.com OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 4 TC 0 Z9 0 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2011 VL 196 IS 6 SU S BP WS37 EP WS46 DI 10.2214/AJR.10.7308 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767JK UT WOS:000290852500005 PM 21606239 ER PT J AU Kambadakone, AR Chaudhary, NA Desai, GS Nguyen, DD Kulkarni, NM Sahani, DV AF Kambadakone, Avinash R. Chaudhary, Naueen A. Desai, Gaurav S. Nguyen, Deanna D. Kulkarni, Naveen M. Sahani, Dushyant V. TI Low-Dose MDCT and CT Enterography of Patients With Crohn Disease: Feasibility of Adaptive Statistical Iterative Reconstruction SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE adaptive statistical iterative reconstruction; Crohn disease; CT enterography; radiation dose ID INFLAMMATORY-BOWEL-DISEASE; IONIZING-RADIATION EXPOSURE; FOLLOW-THROUGH; COMPUTED-TOMOGRAPHY; MR ENTEROGRAPHY; REDUCTION; CHILDREN; EPIDEMIOLOGY; MODULATION; STRATEGIES AB OBJECTIVE. The purpose of this study was to evaluate the image quality and diagnostic performance of low-dose MDCT and CT enterography with adaptive statistical iterative reconstruction (ASIR) in the evaluation of Crohn disease. SUBJECTS AND METHODS. Forty-eight patients (20 men, 28 women; mean age, 33.3 years; range, 17-83 years) with known or suspected Crohn disease who underwent low-dose MDCT and CT enterography with ASIR between December 2008 and December 2009 were included in the study. Twenty-seven patients had previously undergone standard-dose 64-MDCT and CT enterography with filtered back projection (FBP), and those images were used for comparison. The weight-based IV contrast protocol and scan parameters (120 kVp, 5-mm section thickness, 0.5-second rotation, pitch of 1.375, 64 x 0.625 mm detector configuration) were constant for the two techniques except for a higher noise index (x1.3) in the ASIR group. Two blinded readers reviewed 75 randomized MDCT-CT enterographic scans of 48 patients to assess image quality and diagnostic performance in the evaluation of Crohn disease, and the radiation dose for the studies was estimated. RESULTS. All 75 MDCT and CT enterographic scans had acceptable quality for diagnostic interpretation. Findings of Crohn disease were seen on 63 of 75 scans (84%). Low-dose scans in the ASIR group had optimal image quality and were rated comparable to or better than standard-dose FBP images (mean score, 4.2 vs 3.87; p = 0.007). The subjective image noise score (mean, 1.43 vs 1.58; p = 0.2) and objective image noise measurements were lower for ASIR images (p < 0.001). Low-dose studies with ASIR allowed average dose reduction of 34.5% compared with standard-dose scans with FBP (volume CT dose index for ASIR, 7.7 +/- 2.1 mGy; for FBP, 12 +/- 5.5 mGy; p < 0.01). CONCLUSION. Low-dose MDCT and CT enterographic studies reconstructed with ASIR were of appropriate quality for confident evaluation of the manifestations of Crohn disease while allowing approximately 34% dose reduction in comparison with FBP technique. C1 [Kambadakone, Avinash R.; Chaudhary, Naueen A.; Desai, Gaurav S.; Kulkarni, Naveen M.; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Nguyen, Deanna D.] Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 38 TC 64 Z9 65 U1 0 U2 14 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2011 VL 196 IS 6 BP W743 EP W752 DI 10.2214/AJR.10.5303 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767JX UT WOS:000290854000012 PM 21606263 ER PT J AU Li, XH Zhang, D Liu, B AF Li, Xinhua Zhang, Da Liu, Bob TI Automated Extraction of Radiation Dose Information From CT Dose Report Images SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT dose image; optical character recognition; text extraction ID COMPUTED-TOMOGRAPHY AB OBJECTIVE. The purpose of this article is to describe the development of an automated tool for retrieving texts from CT dose report images. CONCLUSION. Optical character recognition was adopted to perform text recognitions of CT dose report images. The developed tool is able to automate the process of analyzing multiple CT examinations, including text recognition, parsing, error correction, and exporting data to spreadsheets. The results were precise for total dose-length product (DLP) and were about 95% accurate for CT dose index and DLP of scanned series. C1 [Li, Xinhua; Zhang, Da; Liu, Bob] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Diagnost Imaging Phys,Dept Radiol, Boston, MA 02114 USA. RP Liu, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Diagnost Imaging Phys,Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu NR 4 TC 12 Z9 12 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2011 VL 196 IS 6 BP W781 EP W783 DI 10.2214/AJR.10.5718 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767JX UT WOS:000290854000018 PM 21606269 ER PT J AU Wu, CC Maher, MM Shepard, JAO AF Wu, Carol C. Maher, Michael M. Shepard, Jo-Anne O. TI Complications of CT-Guided Percutaneous Needle Biopsy of the Chest: Prevention and Management SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE complications; CT-guided biopsy; diagnosis of lung cancer; lung biopsy; lung cancer ID ASPIRATION LUNG-BIOPSY; PULMONARY-LESIONS; PNEUMOTHORAX; RISK; HEMORRHAGE AB OBJECTIVE. The objective of this article is to describe potential complications of percutaneous needle biopsy of the chest, discuss the risk factors associated with the development of complications, and explain how to prevent complications and manage complications when they occur. CONCLUSION. Pneumothorax and pulmonary hemorrhage are the most common complications of percutaneous needle biopsy of the chest, whereas air embolism and tumor seeding are extremely rare. Attention to biopsy planning and technique and postprocedural care help to prevent or minimize most potential complications. C1 [Wu, Carol C.; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Div Thorac Imaging & Intervent, Boston, MA 02114 USA. [Maher, Michael M.] Cork Univ, Dept Radiol, Cork, Ireland. [Maher, Michael M.] Mercy Univ Hosp, Cork, Ireland. [Maher, Michael M.] Univ Coll Cork, Cork, Ireland. RP Wu, CC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Thorac Imaging & Intervent, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM cwu8@partners.org NR 16 TC 58 Z9 61 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2011 VL 196 IS 6 BP W678 EP W682 DI 10.2214/AJR.10.4659 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767JX UT WOS:000290854000002 PM 21606253 ER PT J AU Ferrone, CR Konstantinidis, IT Sahani, DV Wargo, JA Castillo, CFD Warshaw, AL AF Ferrone, Cristina R. Konstantinidis, Ioannis T. Sahani, Dushyant V. Wargo, Jennifer A. Castillo, Carlos Fernandez-del Warshaw, Andrew L. TI Twenty-Three Years of the Warshaw Operation for Distal Pancreatectomy With Preservation of the Spleen SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 40th Anniversary Meeting of the American-Pancreatic-Association-and-Japan-Pancreas-Society CY NOV 04-07, 2009 CL Honolulu, HI SP Amer Pancreat Assoc & Japan Pancreas Soc ID CURATIVE LAPAROSCOPIC RESECTION; SPLENIC ARTERY; POSTSPLENECTOMY SEPSIS; SINGLE INSTITUTION; VEIN; SPLENECTOMY; NEOPLASMS; CONSERVATION; CIRCULATION; MORTALITY AB Objective: To describe our series of distal pancreatectomies with preservation of the spleen utilizing the Warshaw operation with a focus on possible long-term complications due to the development of gastric varices. Background: The Warshaw operation was first described in 1988. The splenic vessels are resected and the spleen survives via the short gastric and left gastroepiploic vessels. Methods: Retrospective review of 721 patients who underwent a distal pancreatectomy between February 1986 and February 2009. Results: The spleen was preserved via the Warshaw operation in 158 patients (22%). Median age was 55 years (range 10-85) and 72% were females. Pathologies included: 35 mucinous cystic neoplasms (adenoma 28, borderline 7), 22 intraductal papillary mucinous neoplasms (adenoma 9, borderline 9, cancer 4), 23 serous cystadenomas, 13 other pancreatic cysts, 27 pancreatic endocrine tumors, 16 chronic pancreatitis, 9 ductal adenocarcinomas, and 13 other pathologies. Only 3 (1.9%) patients required a reoperation because of splenic infarction at 3 to 100 days postoperatively because of abdominal pain and/or fever. Median follow-up was 2.7 years (mean 4.5 years, range 0-21 years). There was evidence of perigastric varices in 16 of 65 (25%) patients who had follow-up imaging at a median of 3.4 years, but none of the 158 patients developed gastrointestinal bleeding or hypersplenism. Conclusions: Spleen preservation with the Warshaw operation has a low postoperative failure rate of 1.9%. Radiologic evidence of asymptomatic perigastric varices was identified in 25% of patients. There were no clinical consequences of perigastric varices in any patient during a follow-up period of up to 21 years. C1 [Ferrone, Cristina R.; Konstantinidis, Ioannis T.; Wargo, Jennifer A.; Castillo, Carlos Fernandez-del] Dept Surg, Boston, MA USA. [Warshaw, Andrew L.] Inst Pancreat Canc Res, Boston, MA USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM cferrone@partners.org NR 22 TC 48 Z9 49 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUN PY 2011 VL 253 IS 6 BP 1136 EP 1139 DI 10.1097/SLA.0b013e318212c1e2 PG 4 WC Surgery SC Surgery GA 764WB UT WOS:000290664100014 PM 21394008 ER PT J AU Barker, RH Urgaonkar, S Mazitschek, R Celatka, C Skerlj, R Cortese, JF Tyndall, E Liu, HL Cromwell, M Sidhu, AB Guerrero-Bravo, JE Crespo-Llado, KN Serrano, AE Lin, JW Janse, CJ Khan, SM Duraisingh, M Coleman, BI Angulo-Barturen, I Jimenez-Diaz, MB Magan, N Gomez, V Ferrer, S Martinez, MS Wittlin, S Papastogiannidis, P O'Shea, T Klinger, JD Bree, M Lee, E Levine, M Wiegand, RC Munoz, B Wirth, DF Clardy, J Bathurst, I Sybertz, E AF Barker, Robert H., Jr. Urgaonkar, Sameer Mazitschek, Ralph Celatka, Cassandra Skerlj, Renato Cortese, Joseph F. Tyndall, Erin Liu, Hanlan Cromwell, Mandy Sidhu, Amar Bir Guerrero-Bravo, Jose E. Crespo-Llado, Keila N. Serrano, Adelfa E. Lin, Jing-wen Janse, Chris J. Khan, Shahid M. Duraisingh, Manoj Coleman, Bradley I. Angulo-Barturen, Inigo Belen Jimenez-Diaz, Maria Magan, Noemi Gomez, Vanesa Ferrer, Santiago Santos Martinez, Maria Wittlin, Sergio Papastogiannidis, Petros O'Shea, Thomas Klinger, Jeffrey D. Bree, Mark Lee, Edward Levine, Mikaela Wiegand, Roger C. Munoz, Benito Wirth, Dyann F. Clardy, Jon Bathurst, Ian Sybertz, Edmund TI Aminoindoles, a Novel Scaffold with Potent Activity against Plasmodium falciparum SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN LIVER-MICROSOMES; IN-VITRO; MALARIA PARASITES; RODENT MALARIA; BERGHEI; RESISTANCE; IDENTIFICATION; ERYTHROCYTES; ARTEMISININ; INFECTION AB This study characterizes aminoindole molecules that are analogs of Genz-644442. Genz-644442 was identified as a hit in a screen of similar to 70,000 compounds in the Broad Institute's small-molecule library and the ICCB-L compound collection at Harvard Medical School. Genz-644442 is a potent inhibitor of Plasmodium falciparum in vitro (50% inhibitory concentrations [IC(50)s], 200 to 285 nM) and inhibits P. berghei in vivo with an efficacy of > 99% in an adapted version of Peters' 4-day suppressive test (W. Peters, Ann. Trop. Med. Parasitol. 69: 155-171, 1975). Genz-644442 became the focus of medicinal chemistry optimization; 321 analogs were synthesized and were tested for in vitro potency against P. falciparum and for in vitro absorption, distribution, metabolism, and excretion (ADME) properties. This yielded compounds with IC(50)s of approximately 30 nM. The lead compound, Genz-668764, has been characterized in more detail. It is a single enantiomer with IC(50)s of 28 to 65 nM against P. falciparum in vitro. In the 4-day P. berghei model, when it was dosed at 100 mg/kg of body weight/day, no parasites were detected on day 4 postinfection. However, parasites recrudesced by day 9. Dosing at 200 mg/kg/day twice a day resulted in cures of 3/5 animals. The compound had comparable activity against P. falciparum blood stages in a humanengrafted NOD-scid mouse model. Genz-668764 had a terminal half-life of 2.8 h and plasma trough levels of 41 ng/ml when it was dosed twice a day orally at 55 mg/kg/day. Seven-day rat safety studies showed a no-observableadverse- effect level (NOAEL) at 200 mg/kg/day; the compound was not mutagenic in Ames tests, did not inhibit the hERG channel, and did not have potent activity against a broad panel of receptors and enzymes. Employing allometric scaling and using in vitro ADME data, the predicted human minimum efficacious dose of Genz-668764 in a 3-day once-daily dosing regimen was 421 mg/day/70 kg, which would maintain plasma trough levels above the IC(90) against P. falciparum for at least 96 h after the last dose. The predicted human therapeutic index was approximately 3, on the basis of the exposure in rats at the NOAEL. We were unable to select for parasites with > 2-fold decreased sensitivity to the parent compound, Genz-644442, over 270 days of in vitro culture under drug pressure. These characteristics make Genz-668764 a good candidate for preclinical development. C1 [Barker, Robert H., Jr.; Celatka, Cassandra; Skerlj, Renato; Liu, Hanlan; Cromwell, Mandy; O'Shea, Thomas; Klinger, Jeffrey D.; Bree, Mark; Lee, Edward; Levine, Mikaela; Sybertz, Edmund] Genzyme Corp, Waltham, MA 02451 USA. [Urgaonkar, Sameer; Mazitschek, Ralph; Cortese, Joseph F.; Tyndall, Erin; Wiegand, Roger C.; Munoz, Benito] 7 Cambridge Ctr, Infect Dis Initiat Program, Broad Inst, Cambridge, MA 02142 USA. [Guerrero-Bravo, Jose E.; Crespo-Llado, Keila N.; Serrano, Adelfa E.] Univ Puerto Rico, Sch Med, Dept Microbiol & Med Zool, San Juan, PR 00936 USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Lin, Jing-wen; Janse, Chris J.; Khan, Shahid M.] Leiden Univ Med Ctr LUMC, Leiden Malaria Res Grp, Ctr Infect Dis, NL-2333 ZA Leiden, Netherlands. [Sidhu, Amar Bir; Duraisingh, Manoj; Coleman, Bradley I.; Wirth, Dyann F.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Angulo-Barturen, Inigo; Belen Jimenez-Diaz, Maria; Magan, Noemi; Gomez, Vanesa; Ferrer, Santiago; Santos Martinez, Maria] GlaxoSmithKline Inc, Dis Dev World, Madrid 28760, Spain. [Wittlin, Sergio; Papastogiannidis, Petros] Swiss Trop & Publ Hlth Inst, CH-4002 Basel, Switzerland. [Wittlin, Sergio; Papastogiannidis, Petros] Univ Basel, CH-4056 Basel, Switzerland. [Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Bathurst, Ian] Med Malaria Venture, CH-1215 Geneva, Switzerland. RP Barker, RH (reprint author), Genzyme Corp, 153 2nd Ave, Waltham, MA 02451 USA. EM Robert.barker@genzyme.com RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X FU Broad Institute; Medicines for Malaria Venture; Humanitarian Assistance for Neglected Diseases Initiative at Genzyme Corporation; China Scholarship Council; [NIH-RCMI-NCRR-G12RR030-51] FX This work was supported by SPARC funds from the Broad Institute, with funds from Medicines for Malaria Venture, and with support from the Humanitarian Assistance for Neglected Diseases Initiative at Genzyme Corporation. Partial support for infrastructure to A.E.S. was provided by NIH-RCMI-NCRR-G12RR030-51. J.-W. Lin is supported by a grant from the China Scholarship Council. NR 41 TC 17 Z9 17 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2011 VL 55 IS 6 BP 2612 EP 2622 DI 10.1128/AAC.01714-10 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 765NA UT WOS:000290713400018 PM 21422215 ER PT J AU Ikuta, T Thatte, HS Tang, JX Mukerji, I Knee, K Bridges, KR Wang, S Montero-Huerta, P Joshi, RM Head, CA AF Ikuta, Tohru Thatte, Hemant S. Tang, Jay X. Mukerji, Ishita Knee, Kelly Bridges, Kenneth R. Wang, Sabina Montero-Huerta, Pedro Joshi, Ratan Mani Head, C. Alvin TI Nitric oxide reduces sickle hemoglobin polymerization: Potential role of nitric oxide-induced charge alteration in depolymerization SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Sickle cell disease; Nitric oxide; Oxygen affinity; Anti-sickling; Polymer formation ID ACUTE CHEST SYNDROME; CELL-DISEASE; OXYGEN-AFFINITY; CARBON-MONOXIDE; BLOOD; NUCLEATION; GELATION; METHEMOGLOBIN; MECHANISM; TRANSPORT AB We previously demonstrated that inhaling nitric oxide (NO) increases the oxygen affinity of sickle red blood cells (RBCs) in patients with sickle cell disease (SCD). Our recent studies found that NO lowered the P(50) values of sickle hemoglobin (HbS) hemolysates but did not increase methemoglobin (metHb) levels, supporting the role of NO, but not metHb, in the oxygen affinity of HbS. Here we examine the mechanism by which NO increases HbS oxygen affinity. Because anti-sickling agents increase sickle RBC oxygen affinity, we first determined whether NO exhibits anti-sickling properties. The viscosity of HbS hemolysates, measured by falling ball assays, increased upon deoxygenation: NO treatment reduced the increment. Multiphoton microscopic analyses showed smaller HbS polymers in deoxygenated sickle RBCs and HbS hemolysates exposed to NO. These results suggest that NO inhibits HbS polymer formation and has anti-sickling properties. Furthermore, we found that HbS treated with NO exhibits an isoelectric point similar to that of HbA, suggesting that NO alters the electric charge of HbS. NO HbS adducts had the same elution time as HbA upon high performance liquid chromatography analysis. This study demonstrates that NO may disrupt HbS polymers by abolishing the excess positive charge of HbS, resulting in increased oxygen affinity. (C) 2011 Elsevier Inc. All rights reserved. C1 [Ikuta, Tohru; Wang, Sabina; Montero-Huerta, Pedro; Joshi, Ratan Mani; Head, C. Alvin] Georgia Hlth Sci Univ, Dept Anesthesiol & Perioperat Med, Augusta, GA 30912 USA. [Thatte, Hemant S.] Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Dept Surg, Boston, MA 02301 USA. [Tang, Jay X.] Brown Univ, Dept Phys, Providence, RI 02912 USA. [Mukerji, Ishita] Wesleyan Univ, Mol Biol & Biochem Dept, Middletown, CT 06459 USA. [Knee, Kelly] MIT, Dept Biol, Cambridge, MA 02139 USA. [Bridges, Kenneth R.] Amgen Inc, Hematol Oncol, Thousand Oaks, CA 91320 USA. RP Head, CA (reprint author), Georgia Hlth Sci Univ, Dept Anesthesiol & Perioperat Med, 1120 15th St,BIW-2144, Augusta, GA 30912 USA. EM ahead@georgiahealth.edu FU Southeastern Clinical and Translational Research Institute; National Institutes of Health [P20 MD003383]; Department of Defense/Office of Naval Research FX We thank Dr. Keith Miller for the use of his laboratory and suggestions regarding ESR, Drs. Celia Bonaventura and Carl Rosow for their helpful comments, and Nadine Odo for editing. We are grateful to Yuchiao Chang for statistical analysis. We also thank INO-Therapeutics for providing the NO gas. This study was supported in part by a Southeastern Clinical and Translational Research Institute grant (T.I.) and P20 MD003383 (T.I.) from the National Institutes of Health, and a grant from the Department of Defense/Office of Naval Research (H.S.T.). NR 55 TC 7 Z9 7 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 1 PY 2011 VL 510 IS 1 BP 53 EP 61 DI 10.1016/j.abb.2011.03.013 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 768JJ UT WOS:000290929900007 PM 21457702 ER PT J AU Iverson, KM Resick, PA Suvak, MK Walling, S Taft, CT AF Iverson, Katherine M. Resick, Patricia A. Suvak, Michael K. Walling, Sherry Taft, Casey T. TI Intimate Partner Violence Exposure Predicts PTSD Treatment Engagement and Outcome in Cognitive Processing Therapy SO BEHAVIOR THERAPY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ASSAULT VICTIMS; BATTERED WOMEN; PROLONGED EXPOSURE; TRAUMA THERAPY; RISK-FACTORS; LONGITUDINAL DATA; CLINICAL-TRIAL; FEMALE VICTIMS; ABUSE AB Intimate partner violence (IPV) exposure was examined as a predictor of treatment engagement (i.e., starting and completing therapy) and treatment outcome in 150 women taking part in a dismantling study of cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD; Resick et al., 2008). Results indicate that women in a current intimate relationship with recent IPV (i.e., past year) were less likely to begin treatment relative to women who reported past IPV only or no history of IPV. For women who began treatment, IPV exposure was not predictive of whether or not they completed treatment. Among women who began treatment, the frequency of IPV was associated with treatment outcome such that women who experienced more frequent IPV exhibited larger reductions in PTSD and depression symptoms over the course of treatment, but experienced similar levels of PTSD and depression severity at the 6-month follow-up. Findings highlight the importance of targeting treatment engagement among women who report recent IPV and suggest that women who have experienced frequent IPV respond well to CPT treatment in spite of their IPV experiences. C1 [Iverson, Katherine M.; Resick, Patricia A.; Suvak, Michael K.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Iverson, Katherine M.; Resick, Patricia A.; Suvak, Michael K.; Taft, Casey T.] Boston Univ, Boston, MA 02215 USA. [Walling, Sherry] Fresno Pacific Univ, Fresno, CA USA. [Taft, Casey T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. RP Iverson, KM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM Katherine.Iverson@va.gov FU NIMH NIH HHS [R01 MH051509, R01 MH051509-05, R01-MH51509, T32 MH019836, T32MH019836] NR 58 TC 11 Z9 12 U1 4 U2 17 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD JUN PY 2011 VL 42 IS 2 BP 236 EP 248 DI 10.1016/j.beth.2010.06.003 PG 13 WC Psychology, Clinical SC Psychology GA 763XT UT WOS:000290593700007 PM 21496509 ER PT J AU Gros, DF Yoder, M Tuerk, PW Lozano, BE Acierno, R AF Gros, Daniel F. Yoder, Matthew Tuerk, Peter W. Lozano, Brian E. Acierno, Ron TI Exposure Therapy for PTSD Delivered to Veterans via Telehealth: Predictors of Treatment Completion and Outcome and Comparison to Treatment Delivered in Person SO BEHAVIOR THERAPY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; PSYCHOMETRIC PROPERTIES; PROLONGED EXPOSURE; TELEPSYCHIATRY; VIDEOCONFERENCE; TELEMEDICINE; SERVICES; SCALES; SAMPLE AB Recent research has focused on the effectiveness of evidence-based psychotherapy delivered via telehealth services. Unfortunately to date, the majority of studies employ very small samples and limited predictor and moderator variables. To address these concerns and further replicate and extend the literature on telehealth, the present study investigated the effectiveness of 12-session exposure therapy delivered either via telehealth (n=62) or in person (n=27) in veterans with posttraumatic stress disorder (PTSD). Findings demonstrated that although older veterans and Vietnam veterans were more likely to complete the telehealth treatment, telehealth findings were not influenced by patient age, sex, race, combat theater, or disability status. Exposure therapy delivered via telehealth was effective in reducing the symptoms of PTSD, anxiety, depression, stress, and general impairment with large effect sizes. Interestingly, exposure therapy via telehealth was less effective than exposure therapy delivered in person; however, lack of random assignment to condition limits conclusions of differential effectiveness. Overall, these findings support the utility of telehealth services to provide effective, evidence-based psychotherapies. C1 [Gros, Daniel F.] Ralph H Johnson Vet Adm Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. Med Univ S Carolina, Charleston, SC USA. RP Gros, DF (reprint author), Ralph H Johnson Vet Adm Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu RI Schueter, nicos/A-3625-2014 NR 34 TC 69 Z9 70 U1 3 U2 11 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD JUN PY 2011 VL 42 IS 2 BP 276 EP 283 DI 10.1016/j.beth.2010.07.005 PG 8 WC Psychology, Clinical SC Psychology GA 763XT UT WOS:000290593700010 PM 21496512 ER PT J AU Williams, SB D'Amico, AV Weinberg, AC Gu, XM Lipsitz, SR Hu, JC AF Williams, Stephen B. D'Amico, Anthony V. Weinberg, Aaron C. Gu, Xiangmei Lipsitz, Stuart R. Hu, Jim C. TI Population-based determinants of radical prostatectomy surgical margin positivity SO BJU INTERNATIONAL LA English DT Article DE positive margins; prostatectomy; minimally invasive; surgeon volume; outcomes ID LEARNING-CURVE; CANCER; OUTCOMES; TRENDS; RISK; RADIOTHERAPY; SPECIMENS; LOCATION; SURGEONS; VOLUME AB OBJECTIVE To characterize factors associated with positive surgical margins (PSMs) and derive population-based PSM cutoffs to evaluate surgeon performance in radical prostatectomy (RP). PATIENTS AND METHODS SEER-Medicare data were used to identify 4247 men diagnosed with prostate cancer during 2004-2005 who underwent RP up to 2006. We performed logistic regression to assess the impact of tumour characteristics, surgeon volume and surgical approach on the likelihood of PSMs for pT2 and PT3a disease. Moreover, we derived 25th and 10th percentile cutoffs from binomial distribution equations. RESULTS Overall, 19.4% of men experienced PSMs with a pT2 vs pT3a PSM rate of 14.9% vs 42% (P < 0.001). Extrapolating from our population-based results, a surgeon incurring more than three PSMs in 10 cases of pT2 disease performed below the 25th percentile. There was a trend for fewer PSMs with minimally invasive vs open RP (17.4% vs 20.1%, P = 0.086), and the PSM rate also decreased over the study period from 21.3% in 2004 to 16.6% in 2006 (P = 0.028) with significant geographic variation (P < 0.001). In adjusted analyses, temporal and geographic variation in PSM persisted, and men with high (odds ratio 3.68, 95% CI 2.82-4.81) and intermediate (odds ratio 2.52, 95% CI 2.03-3.13) vs low-risk disease were at greater odds to experience PSMs. Notably, neither surgical approach nor surgeon volume was significantly associated with PSMs. CONCLUSION Our population-based PSM benchmarks allow identification of under-performing outliers who may seek courses or video self-study to improve outcomes. There was significant temporal and geographic variation in PSMs but neither surgeon volume nor surgical approach was associated with PSMs. C1 [Williams, Stephen B.; Weinberg, Aaron C.; Hu, Jim C.] Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. [Gu, Xiangmei; Lipsitz, Stuart R.; Hu, Jim C.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Hu, Jim C.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Hu, JC (reprint author), Brigham & Womens Hosp, Div Neurol, ASBII-3,45 Francis St, Boston, MA 02115 USA. EM jhu2@partners.org OI weinberg, aaron/0000-0002-0957-5703 FU Department of Defense [PC073261] FX This work was supported by a Department of Defense Prostate Cancer Physician Training Award (PC073261) presented to Dr Hu. This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, National Cancer Institute; the Office of Research, Development and Information, Centers for Medicare and Medicaid Services; Information Management Services Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumour registries in the creation of the SEER-Medicare database. NR 34 TC 12 Z9 12 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUN PY 2011 VL 107 IS 11 BP 1734 EP 1740 DI 10.1111/j.1464-410X.2010.09662.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 766GW UT WOS:000290770000005 PM 20942827 ER PT J AU Roland, M Rao, SR Sibbald, B Hann, M Harrison, S Walter, A Guthrie, B Desroches, C Ferris, TG Campbell, EG AF Roland, Martin Rao, Sowmya R. Sibbald, Bonnie Hann, Mark Harrison, Stephen Walter, Alex Guthrie, Bruce Desroches, Catherine Ferris, Timothy G. Campbell, Eric G. TI Professional values and reported behaviours of doctors in the USA and UK: quantitative survey SO BMJ QUALITY & SAFETY LA English DT Article ID MEDICAL PROFESSIONALISM; MILLENNIUM; PHYSICIANS; CHARTER; CARE; FACE AB Background: The authors aimed to determine US and UK doctors' professional values and reported behaviours, and the extent to which these vary with the context of care. Method: 1891 US and 1078 UK doctors completed the survey (64.4% and 40.3% response rate respectively). Multivariate logistic regression was used to compare responses to identical questions in the two surveys. Results: UK doctors were more likely to have developed practice guidelines (82.8% UK vs 49.6% US, p<0.001) and to have taken part in a formal medical error-reduction programme (70.9% UK vs 55.7% US, p<0.001). US doctors were more likely to agree about the need for periodic recertification (completely agree 23.4% UK vs 53.9% US, p<0.001). Nearly a fifth of doctors had direct experience of an impaired or incompetent colleague in the previous 3 years. Where the doctor had not reported the colleague to relevant authorities, reasons included thinking that someone else was taking care of the problem, believing that nothing would happen as a result, or fear of retribution. UK doctors were more likely than US doctors to agree that significant medical errors should always be disclosed to patients. More US doctors reported that they had not disclosed an error to a patient because they were afraid of being sued. Discussion: The context of care may influence both how professional values are expressed and the extent to which behaviours are in line with stated values. Doctors have an important responsibility to develop their healthcare systems in ways which will support good professional behaviour. C1 [Roland, Martin] Univ Cambridge, Cambridge Ctr Hlth Serv Res, Inst Publ Hlth, Cambridge CB2 0SR, England. [Rao, Sowmya R.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Sibbald, Bonnie; Hann, Mark; Harrison, Stephen; Walter, Alex] Univ Manchester, Natl Primary Care Res & Dev Ctr, Manchester, Lancs, England. [Guthrie, Bruce] Univ Dundee, Ctr Primary Care & Populat Res, Dundee, Scotland. [Desroches, Catherine; Ferris, Timothy G.; Campbell, Eric G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. RP Roland, M (reprint author), Univ Cambridge, Cambridge Ctr Hlth Serv Res, Inst Publ Hlth, Robinson Way, Cambridge CB2 0SR, England. EM mr108@cam.ac.uk OI Roland, Martin/0000-0002-8533-3060; Guthrie, Bruce/0000-0003-4191-4880 FU Nuffield Trust; ABIM Foundation; Institute on Medicine FX We are grateful to the Nuffield Trust who funded the UK survey, to the ABIM Foundation who part-funded the US survey and to the Institute on Medicine as a Profession who funded the US survey and provided financial support for focus groups held in the UK during the development of the questionnaire. NR 21 TC 19 Z9 19 U1 1 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JUN PY 2011 VL 20 IS 6 BP 515 EP 521 DI 10.1136/bmjqs.2010.048173 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 768DB UT WOS:000290910600007 PM 21383386 ER PT J AU Swensen, SJ Kaplan, GS Meyer, GS Nelson, EC Hunt, GC Pryor, DB Weissberg, JI Daley, J Yates, GR Chassin, MR AF Swensen, Stephen J. Kaplan, Gary S. Meyer, Gregg S. Nelson, Eugene C. Hunt, Gordon C. Pryor, David B. Weissberg, Jed I. Daley, Jennifer Yates, Gary R. Chassin, Mark R. TI Controlling healthcare costs by removing waste: what American doctors can do now SO BMJ QUALITY & SAFETY LA English DT Article ID CONCEPTUAL-FRAMEWORK; RANDOMIZED-TRIAL; ANTIBIOTIC USE; VERTEBROPLASTY; FRACTURES; QUALITY; IMPACT AB Healthcare costs are unsustainable. The authors propose a solution to control costs without rationing (deliberate withholding of effective care) or payment reductions to doctors and hospitals. Three physician-led strategies comprise this solution: reduce (1) overuse of health services, (2) preventable complications and (3) waste within healthcare processes. These challenges know no borders. C1 [Swensen, Stephen J.] Mayo Clin, Rochester, MN 55905 USA. [Kaplan, Gary S.] Virginia Mason Hlth Syst, Seattle, WA USA. [Meyer, Gregg S.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Meyer, Gregg S.] Massachusetts Gen Phys Org, Boston, MA USA. [Nelson, Eugene C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Hunt, Gordon C.] Sutter Hlth, Sacramento, CA USA. [Pryor, David B.] Ascens Hlth, St Louis, MO USA. [Weissberg, Jed I.] Kaiser Permanente, Qual & Care Delivery Excellence, Oakland, CA USA. [Daley, Jennifer] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. [Daley, Jennifer] Univ Massachusetts, Sch Med, Worcester, MA USA. [Yates, Gary R.] Sentara Healthcare, Norfolk, VA USA. [Chassin, Mark R.] Int Joint Commiss, Oak Brook Terrace, IL USA. RP Swensen, SJ (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM swensen.stephen@mayo.edu NR 39 TC 14 Z9 14 U1 1 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JUN PY 2011 VL 20 IS 6 BP 534 EP 537 DI 10.1136/bmjqs.2010.049213 PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 768DB UT WOS:000290910600010 PM 21339313 ER PT J AU Ramsey, B Bai, T Newell, AH Troxell, M Park, B Olson, S Keenan, E Luoh, SW AF Ramsey, Betsy Bai, Tao Newell, Amy Hanlon Troxell, Megan Park, Byung Olson, Susan Keenan, Edward Luoh, Shiuh-Wen TI GRB7 protein over-expression and clinical outcome in breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Biomarker; Prognostic marker; Signal transduction; Gene amplification; Oncogenes; HER-2 gene; GRB7 gene ID IN-SITU HYBRIDIZATION; RECEPTOR-BOUND PROTEIN-7; HER-2 NEU ONCOGENE; AMERICAN-SOCIETY; ERBB2 AMPLICON; AMPLIFICATION; GENES; RECOMMENDATIONS; TUMORIGENESIS; ACTIVATION AB The growth factor receptor-bound protein-7 gene (GRB7) encodes a multi-domain signal transduction molecule. The purpose of this study was to examine the clinical significance of GRB7 protein expression in human breast cancer. Western blotting analysis of protein extracts from 563 annotated frozen breast tumors was performed. Expression status of GRB7 and HER-2 was correlated with clinical covariates and outcomes. Cox proportional hazards were used to identify factors associated with breast cancer-free interval. The median follow-up was 71 months. P values < 0.05 were considered statistically significant (two-sided). A discrepancy between HER-2 and GRB7 protein over-expression was observed. GRB7 protein over-expression was associated with negative estrogen and progesterone receptor status, higher tumor grade, larger primary tumor size, (more) axillary lymph node involvement, higher clinical stage, and shortened breast cancer-free interval. HER-2 protein over-expression was associated only with higher tumor grade. Multi-variate analysis revealed that GRB7 protein over-expression was an independent adverse prognostic factor for breast cancer-free interval (hazard ratio 1.69, 95% confidence interval 1.07-2.67; P = 0.024). The same was true of the subset of patients who did not receive any adjuvant systemic therapy (hazard ratio 1.68, 95% confidence interval 1.16-2.31; P = 0.0055). Using FISH analysis, 32/32 (100%; 95% CI 89-100%) tumors which over-expressed both HER-2 and GRB7 proteins and 1/35 (3%; 95% CI 0-15%) tumors with HER-2 but no GRB7 protein over-expression with Western blotting analysis demonstrated HER-2 gene amplification. GRB7 protein over-expression is an independent adverse prognostic factor in human breast cancer. C1 [Bai, Tao; Luoh, Shiuh-Wen] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Ramsey, Betsy; Keenan, Edward] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Bai, Tao; Luoh, Shiuh-Wen] Portland VA Med Ctr, Portland, OR 97239 USA. [Newell, Amy Hanlon; Olson, Susan] Oregon Hlth & Sci Univ, Dept Med & Mol Genet, Portland, OR 97239 USA. [Troxell, Megan] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Park, Byung] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Ramsey, Betsy; Bai, Tao; Newell, Amy Hanlon; Troxell, Megan; Park, Byung; Olson, Susan; Keenan, Edward; Luoh, Shiuh-Wen] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. RP Luoh, SW (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, 3181 SW Sam Jackson Pk Rd,MC L586, Portland, OR 97239 USA. EM luohs@ohsu.edu OI /0000-0003-3516-7516 FU Department of Veterans Affairs; Portland VA Research Foundation; OHSU; OHSU Foundation FX The work is supported by Department of Veterans Affairs, Portland VA Research Foundation, OHSU Presidential Bridge Award, and OHSU Foundation. We are grateful to the technical assistance provided by the Histology Shared Resources at the Knight Cancer Institute, OHSU. NR 31 TC 19 Z9 20 U1 0 U2 1 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 JUN PY 2011 VL 127 IS 3 BP 659 EP 669 DI 10.1007/s10549-010-1010-0 PG 11 WC Oncology SC Oncology GA 766UH UT WOS:000290811500008 PM 20635137 ER PT J AU Bortfeld, T Jeraj, R AF Bortfeld, T. Jeraj, R. TI The physical basis and future of radiation therapy SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; TARGET VOLUME DELINEATION; SQUAMOUS-CELL CARCINOMA; MULTICRITERIA OPTIMIZATION; LUNG-CANCER; ADAPTIVE RADIOTHERAPY; DOSE DISTRIBUTIONS; NORMAL TISSUE; NECK-CANCER; PROTON-BEAM AB The remarkable progress in radiation therapy over the last century has been largely due to our ability to more effectively focus and deliver radiation to the tumour target volume. Physics discoveries and technology inventions have been an important driving force behind this progress. However, there is still plenty of room left for future improvements through physics, for example image guidance and four-dimensional motion management and particle therapy, as well as increased efficiency of more compact and cheaper technologies. Bigger challenges lie ahead of physicists in radiation therapy beyond the dose localisation problem, for example in the areas of biological target definition, improved modelling for normal tissues and tumours, advanced multicriteria and robust optimisation, and continuous incorporation of advanced technologies such as molecular imaging. The success of physics in radiation therapy has been based on the continued "fuelling" of the field with new discoveries and inventions from physics research. A key to the success has been the application of the rigorous scientific method. In spite of the importance of physics research for radiation therapy, too few physicists are currently involved in cutting-edge research. The increased emphasis on more "professionalism" in medical physics will tip the situation even more off balance. To prevent this from happening, we argue that medical physics needs more research positions, and more and better academic programmes. Only with more emphasis on medical physics research will the future of radiation therapy and other physics-related medical specialties look as bright as the past, and medical physics will maintain a status as one of the most exciting fields of applied physics. C1 [Bortfeld, T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bortfeld, T.] Harvard Univ, Sch Med, Boston, MA USA. [Jeraj, R.] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. RP Bortfeld, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM tbortfeld@partners.org NR 71 TC 28 Z9 28 U1 0 U2 10 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD JUN PY 2011 VL 84 IS 1002 BP 485 EP 498 DI 10.1259/bjr/86221320 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767HU UT WOS:000290847100007 PM 21606068 ER PT J AU Carabe-Fernandez, A Dale, RG Paganetti, H AF Carabe-Fernandez, A. Dale, R. G. Paganetti, H. TI Repair kinetic considerations in particle beam radiotherapy SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; REJOINING DNA BREAKS; IONIZING-RADIATION; MAMMALIAN-CELLS; ALPHA-PARTICLES; CARBON-IONS; DAMAGE; IRRADIATION; INACTIVATION; MECHANISMS AB Objectives: A second-order repair kinetics model is developed to predict damage repair rates following low or high linear energy transfer (LET) irradiations and to assess the amount of unrepairable damage produced by such radiations. The model is a further development of an earlier version designed to test if low-LET radiation repair processes could be quantified in terms of second-order kinetics. The newer version allows calculation of both the repair rate of the proportion of DNA damages that repair according to second-order kinetics and the proportion of DNA damages that do not repair. Methods: The original and present models are intercompared in terms of their goodness-of-fit to a number of data sets obtained from different ion beams. The analysis demonstrates that the present model provides a better fit to the data in all cases studied. Results: The proportions of unrepairable damage created by radiations of different LET predicted by the new model correspond well with previous studies on the increased effectiveness of high-LET radiations in inducing reproductive cell death. The results show that the original model may underestimate the proportion of unrepaired damage at any given time after its creation as well as failing to predict very slow or unrepairable damage components, which may result from high-LET irradiation. Conclusion: It is suggested that the second-order model presented here offers a more realistic view of the patterns of repair in cell lines or tissues exposed to high-LET radiation. C1 [Carabe-Fernandez, A.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Carabe-Fernandez, A.; Paganetti, H.] Harvard Univ, Sch Med, Boston, MA USA. [Dale, R. G.] Imperial Coll Healthcare NHS Trust, Charing Cross Hosp, Dept Radiat Phys & Radiobiol, London, England. [Dale, R. G.] Univ Oxford, Gray Inst Radiat Oncol & Biol, Oxford, England. RP Carabe-Fernandez, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM acarabe@partners.org FU Cyclotron Trust, UK FX This study was funded in full by the Cyclotron Trust, UK (www.neutrontherapy.co.uk). The authors want to thank Professor Bleddyn Jones for his comments and suggestions about the manuscript. NR 37 TC 4 Z9 4 U1 0 U2 2 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD JUN PY 2011 VL 84 IS 1002 BP 546 EP 555 DI 10.1259/19934996 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767HU UT WOS:000290847100013 PM 21266398 ER PT J AU Harzstark, AL Rosenberg, JE Weinberg, VK Sharib, J Ryan, CJ Smith, DC Pagliaro, LC Beer, TM Liu, G Small, EJ AF Harzstark, Andrea L. Rosenberg, Jonathan E. Weinberg, Vivian K. Sharib, Jeremy Ryan, Charles J. Smith, David C. Pagliaro, Lance C. Beer, Tomasz M. Liu, Glenn Small, Eric J. TI Ixabepilone, Mitoxantrone, and Prednisone for Metastatic Castration-Resistant Prostate Cancer After Docetaxel-Based Therapy A Phase 2 Study of the Department of Defense Prostate Cancer Clinical Trials Consortium SO CANCER LA English DT Article DE prostate cancer; chemotherapy; metastatic; mitoxantrone; ixabepilone; docetaxel ID EPOTHILONE-B ANALOG; ADVANCED BREAST-CANCER; WORKING GROUP; BMS-247550; RECOMMENDATIONS; ANTHRACYCLINE; CHEMOTHERAPY; ANTIGEN; TAXANE AB BACKGROUND: Mitoxantrone plus prednisone and ixabepilone each have modest activity as monotherapy for second-line chemotherapy in patients with docetaxel-refractory castration-resistant prostate cancer. Clinical noncross-resistance was previously observed. Phase 1 testing determined the maximum tolerated dose and dose-limiting toxicities with the combination regimen; a phase 2 study was conducted to evaluate the activity of the combination. METHODS: Patients with metastatic progressive castration-resistant prostate cancer during or after 3 or more cycles of taxane-based chemotherapy enrolled in a phase 2 multicenter study of ixabepilone 35 mg/m(2) and mitoxantrone 12 mg/m(2) administered on Day 1 every 21 days with pegfilgrastim support, along with prednisone 5 mg twice daily. Patients were evaluated for disease response and toxicity. RESULTS: Results are reported for the 56 evaluable patients. Twenty-five (45%; 95% confidence interval [CI], 31%-59%) experienced confirmed >= 50% prostate-specific antigen (PSA) declines, 33 (59%; 95% CI, 45%-72%) experienced confirmed >= 30% PSA declines, and 8 of 36 patients (22%; 95% CI, 10%-39%) with measurable disease experienced objective responses. Median time to PSA or objective progression was 4.4 months (95% CI, 3.5-5.6), and median progression-free survival was also 4.4 months (95% CI, 3.0-6.0). Median overall survival was 12.5 months (95% CI, 10.2-15.9). Thirty-two percent of patients experienced grade 3 of 4 neutropenia, and 11% experienced grade 3 or higher neutropenic infections, including 1 treatment-related death. Grade 2 and 3 neuropathy occurred in 11% and 12.5% of patients, respectively. CONCLUSIONS: These results suggest that the combination of ixabepilone and mitoxantrone is both feasible and active in castration-resistant prostate cancer and requires dosing with pegfilgrastim. Cancer 2011; 117: 2419-25. (C) 2010 American Cancer Society. C1 [Harzstark, Andrea L.] Univ Calif San Francisco, Dept Med, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Rosenberg, Jonathan E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, David C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Pagliaro, Lance C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Beer, Tomasz M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Liu, Glenn] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. RP Harzstark, AL (reprint author), Univ Calif San Francisco, Dept Med, Helen Diller Family Comprehens Canc Ctr, 1600 Divisadero St,Box 1711, San Francisco, CA 94143 USA. EM andrea.harzstark@ucsf.edu FU National Cancer Institute, Department of Defense Prostate Cancer Clinical Trials Consortium [W81XWH-05-1-175, W81XWH-06-01-0256]; Prostate Cancer Foundation FX This study was supported in part by: Department of Defense Physicians Research Training Grant No. W81XWH-05-1-175 from the Cancer Therapy Evaluation Program of the National Cancer Institute, Department of Defense Prostate Cancer Clinical Trials Consortium Grant No. W81XWH-06-01-0256, and the Prostate Cancer Foundation. NR 13 TC 5 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2011 VL 117 IS 11 BP 2419 EP 2425 DI 10.1002/cncr.25810 PG 7 WC Oncology SC Oncology GA 767ME UT WOS:000290859900013 PM 24048789 ER PT J AU Tan, ASL Bourgoin, A Gray, SW Armstrong, K Hornik, RC AF Tan, Andy S. L. Bourgoin, Angel Gray, Stacy W. Armstrong, Katrina Hornik, Robert C. TI How Does Patient-Clinician Information Engagement Influence Self-Reported Cancer-Related Problems? Findings From a Longitudinal Analysis SO CANCER LA English DT Article DE patient-clinician communication; self-reported outcomes; cancer; survivor ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; CENTERED CARE; COMMUNICATION; OUTCOMES; IMPROVE; IMPACT; NEEDS AB BACKGROUND: Past research has linked patient-physician communication with improved emotional, physical, and social health. One component of communication, patient-clinician information engagement (PCIE), predicts improved short-term patient-reported outcomes, such as treatment satisfaction, through perceptions of feeling informed. However, to the authors' knowledge, the relation between PCIE and longer term cancer-related problems has not been examined previously. The authors examined the influence of PCIE on self-reported problems associated with cancer diagnosis and treatment based on a longitudinal survey among a randomly selected sample from the 2005 Pennsylvania Cancer Registry. METHODS: In total, 1293 respondents were surveyed who were diagnosed with colorectal, breast, or prostate cancers during 2006 and 2007. The baseline response rate was 64%, and the retention rate was 65%. The authors predicted an index of cancer-related problems at 1-year follow-up with the baseline cancer-related problem index and PCIE, controlling for demographic and clinical factors using regression analyses. The mean age of participants was 65 years, approximately 50% were women, and 86% were white. RESULTS: Having more cancer-related problems and PCIE at baseline significantly predicted more cancer-related problems at follow-up. In addition, baseline cancer-related problems and PCIE interacted significantly (P=.01): PCIE was associated with more cancer-related problems at follow-up among participants who reported more symptoms rather than fewer symptoms at baseline. CONCLUSIONS: If respondents reported engaging more with their physicians at baseline, then they reported experiencing more cancer-related issues at follow-up; this pattern was stronger among those who reported more baseline problems. The current results indicated that increased discussion of cancer information with physicians may maintain the salience of these problems in cancer survivors' minds over time. Cancer 2011; 117: 256-976. (C) 2011 American Cancer Society. C1 [Tan, Andy S. L.; Bourgoin, Angel; Armstrong, Katrina; Hornik, Robert C.] Univ Penn, Annenberg Sch Commun, Ctr Excellence Canc Commun Res, Philadelphia, PA 19146 USA. [Gray, Stacy W.] Dana Farber Canc Inst, Ctr Community Based Res, Dept Med Oncol, Boston, MA 02115 USA. [Armstrong, Katrina] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19146 USA. [Armstrong, Katrina] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19146 USA. [Armstrong, Katrina] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19146 USA. RP Tan, ASL (reprint author), Univ Penn, Annenberg Sch Commun, Ctr Excellence Canc Commun Res, 3620 Walnut St, Philadelphia, PA 19146 USA. EM atan@asc.upenn.edu RI Tan, Andy/H-1102-2012; OI Hornik, Robert/0000-0002-2148-8805 FU National Cancer Institute [5P50CA095856-05] FX Research support was received thorough Grant 5P50CA095856-05 from the National Cancer Institute. NR 28 TC 9 Z9 9 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2011 VL 117 IS 11 BP 2569 EP 2576 DI 10.1002/cncr.25804 PG 8 WC Oncology SC Oncology GA 767ME UT WOS:000290859900030 PM 24048804 ER PT J AU Abramson, JS Hochberg, EP AF Abramson, Jeremy S. Hochberg, Ephraim P. TI Reply to Intravenous Methotrexate as Central Nervous System (CNS) Prophylaxis Is Associated With a Low Risk of CNS Recurrence in High-Risk Patients With Diffuse Large B-Cell Lymphoma SO CANCER LA English DT Letter ID NON-HODGKIN-LYMPHOMA C1 [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02114 USA. OI Abramson, Jeremy/0000-0001-8467-9257 NR 4 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2011 VL 117 IS 11 BP 2580 EP 2581 DI 10.1002/cncr.25788 PG 2 WC Oncology SC Oncology GA 767ME UT WOS:000290859900036 ER PT J AU Anderson, KS Zeng, WY Sasada, T Choi, J Riemer, AB Su, M Drakoulakos, D Kang, YJ Brusic, V Wu, C Reinherz, EL AF Anderson, Karen S. Zeng, Wanyong Sasada, Tetsuro Choi, Jaewon Riemer, Angelika B. Su, Mei Drakoulakos, Donna Kang, Yoon-Joong Brusic, Vladimir Wu, Catherine Reinherz, Ellis L. TI Impaired tumor antigen processing by immunoproteasome-expressing CD40-activated B cells and dendritic cells SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Vaccination; Tumor immunity; Antigen processing; Dendritic cells ID CYTOTOXIC T-CELLS; PRESENTING CELLS; STANDARD PROTEASOME; CANCER-IMMUNOTHERAPY; LYMPHOCYTES; GENERATION; RESPONSES; PEPTIDES; CLEAVAGE; DISTINCT AB Professional APCs, such as dendritic cells, are routinely used in vitro for the generation of cytotoxic T lymphocytes specific for tumor antigens. In addition to dendritic cells, CD40-activated B cells and variant K562 leukemic cells can be readily transfected with nucleic acids for in vitro and in vivo antigen presentation. However, the expression of immunoproteasome components in dendritic cells may preclude display of tumor antigens such as Mart1/MelanA. Here, we use three target epitopes, two derived from tumor antigens [Mart1(26-34) (M26) and Cyp1B1(239-247) (Cyp239)] and one derived from the influenza A viral antigen [FluM1(58-66) (FluM58)], to demonstrate that CD40-activated B cells, like dendritic cells, have a limited capability to process certain tumor antigens. In contrast, the K562 HLA-A*0201 transfectant efficiently processes and presents M26 and Cyp239 as well as the influenza FluM58 epitopes to T cells. These results demonstrate that the choice of target APC for gene transfer of tumor antigens may be limited by the relative efficacy of proteasome components to process certain tumor epitopes. Importantly, K562 can be exploited as an artificial APC, efficient in processing both M26 and Cyp239 epitopes and presumably, by extension, other relevant tumor antigens. C1 [Anderson, Karen S.; Zeng, Wanyong; Sasada, Tetsuro; Choi, Jaewon; Riemer, Angelika B.; Su, Mei; Drakoulakos, Donna; Kang, Yoon-Joong; Brusic, Vladimir; Wu, Catherine; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Anderson, KS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Room HIM416,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM kanderson@partners.org FU deBeaumont Foundation; National Cancer Institute/Avon Foundation [5 P30 CA006516-44, R21 CA115043-2]; Cancer Vaccine Center at the Dana-Farber Cancer Institute FX We thank Dr. Lee Nadler for providing valuable scientific reagents. This study was supported by a research grant from the deBeaumont Foundation and the National Cancer Institute/Avon Foundation (5 P30 CA006516-44, KSA), R21 CA115043-2 (CW) and the Cancer Vaccine Center at the Dana-Farber Cancer Institute. NR 42 TC 4 Z9 4 U1 1 U2 6 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 JUN PY 2011 VL 60 IS 6 BP 857 EP 867 DI 10.1007/s00262-011-0995-5 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA 766QS UT WOS:000290802200010 PM 21400024 ER PT J AU Gaur, SK Friese, JL Sadow, CA Ayyagari, R Binkert, CA Schenker, MP Kulke, M Baum, R AF Gaur, Shantanu K. Friese, Jeremy L. Sadow, Cheryl A. Ayyagari, Rajasekhara Binkert, Christoph A. Schenker, Matthew P. Kulke, Matthew Baum, Richard TI Hepatic Arterial Chemoembolization Using Drug-Eluting Beads in Gastrointestinal Neuroendocrine Tumor Metastatic to the Liver SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Embolization; Chemoembolization; Carcinoid; Liver; Neuroendocrine tumor ID DIGESTIVE ENDOCRINE TUMORS; ISLET-CELL CARCINOMA; INTRAARTERIAL CHEMOTHERAPY; OCTREOTIDE ACETATE; EMBOLIZATION; DOXORUBICIN; MANAGEMENT; COMPLICATIONS; FLUOROURACIL; EXPERIENCE AB Purpose This study was designed to evaluate short (<3 months) and intermediate-term (>3 months) follow-up in patients with metastatic neuroendocrine tumor to the liver who underwent hepatic arterial chemoembolization with drug-eluting beads at a single institution. Methods Institutional review board approval was obtained for this retrospective review. All patients who were treated with 100-300 or 300-500 mu m drug-eluting LC Beads (Biocompatibles, UK) preloaded with doxorubicin (range, 50-100 mg) for GI neuroendocrine tumor metastatic to the liver from June 2004 to June 2009 were included. CT and MRI were evaluated for progression using Response Evaluation Criteria In Solid Tumors (RE-CIST) or European Association for the Study of the Liver (EASL) criteria. Short-term (<3 months) and intermediateterm (>3 months) imaging response was determined and Kaplan-Meier survival curves were plotted. Results Thirty-eight drug-eluting bead chemoembolization procedures were performed on 32 hepatic lobes, comprising 21 treatment cycles in 18 patients. All procedures were technically successful with two major complications (biliary injuries). At short-term follow-up (<3 months), 22 of 38 (58%) procedures and 10 of 21 (48%) treatment cycles produced an objective response (OR) with the remainder having stable disease (SD). At intermediate-term follow-up (mean, 445 days; range, 163-1247), 17 of 26 (65%) procedures and 8 of 14 (57%) treatment cycles produced an OR. Probability of progressing was approximately 52% at 1 year with a median time to progression of 419 days. Conclusions Drug-eluting bead chemoembolization is a reasonable alternative to hepatic arterial embolization and chemoembolization for the treatment of metastatic neuroendocrine tumor to the liver. C1 [Binkert, Christoph A.; Baum, Richard] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Binkert, Christoph A.] Kantonsspital Winterthur, Dept Radiol, CH-8401 Winterthur, Switzerland. [Kulke, Matthew] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Baum, R (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM rbaum@partners.org OI Gaur, Shantanu/0000-0003-0876-0517 FU Society for Interventional Radiology Foundation; Paul & Daisy Soros Fellowship FX SKG was supported by the Society for Interventional Radiology Foundation Student Research Grant and the Paul & Daisy Soros Fellowship. NR 42 TC 23 Z9 23 U1 0 U2 0 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 JUN PY 2011 VL 34 IS 3 BP 566 EP 572 DI 10.1007/s00270-011-0122-1 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 765TA UT WOS:000290730300018 PM 21431978 ER PT J AU Bande, D Abbara, S Kalva, SP AF Bande, Dinesh Abbara, Suhny Kalva, Sanjeeva P. TI Acute Renal Infarction Secondary to Calcific Embolus from Mitral Annular Calcification SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Imaging; Intraarterial; Kidney/Renal ID EMBOLIZATION; ARTERY AB We report a case of a 62-year-old man who presented with right groin pain who subsequently was found to have a renal infarct secondary to calcific embolus from mitral annular calcification on CT and angiography. We briefly review the literature and discuss the importance of this entity in clinical practice. C1 [Abbara, Suhny; Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bande, Dinesh] Univ N Dakota, Sch Med & Hlth Sci, Dept Med, Grand Forks, ND 58201 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB-270,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org FU Amirsys Inc.; Elsevier FX Dr. Bande declares no conflict of interest. Dr. Abbara declares the following conflicts of interest: Board membership in SCCT and CBCCT, Consultancy at Partners Imaging, Magellan Healthcare and Perceptive Informatics, Honoraria from Siemens, and Royalties from Amirsys Inc. and Elsevier. Dr. Kalva declares the following conflicts of interest: Consultancy and Honoraria from Cordis Endovascular, Research Grant from Angiodynamics and Cook, and Royalties from Amirsys Inc. and Elsevier. NR 6 TC 2 Z9 3 U1 0 U2 0 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 JUN PY 2011 VL 34 IS 3 BP 647 EP 649 DI 10.1007/s00270-010-9944-5 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 765TA UT WOS:000290730300031 PM 20661568 ER PT J AU Connors, G Todoran, TM Engelson, BA Sobieszczyk, PS Eisenhauer, AC Kinlay, S AF Connors, Gerard Todoran, Thomas M. Engelson, Brian A. Sobieszczyk, Piotr S. Eisenhauer, Andrew C. Kinlay, Scott TI Percutaneous Revascularization of Long Femoral Artery Lesions for Claudication: Patency Over 2.5 Years and Impact of Systematic Surveillance SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE peripheral artery disease; percutaneous peripheral interventions; stents; long-term outcomes; PVD-peripheral vascular disease ID NITINOL STENT IMPLANTATION; MAJOR VASCULAR-SURGERY; ENDOVASCULAR TREATMENT; BALLOON ANGIOPLASTY; POPLITEAL ARTERIES; RANDOMIZED-TRIAL; LOWER-EXTREMITY; SAPHENOUS-VEIN; FOLLOW-UP; TASC-II AB Background: Angioplasty and stenting are preferred treatments for revascularizing femoral artery lesions up to 100 mm, but surgical bypass is recommended for longer lesions. We assessed long-term patency after percutaneous revascularization of long femoral artery lesions for claudication with intensive out-patient surveillance. Methods: We followed a cohort of 111 consecutive patients receiving angioplasty or stenting in 142 limbs in two institutions. Patients were followed for 2.5 years, and event curves and multivariable survival analysis used to compare outcomes in three groups according to lesion length (< 100 mm, 100-200 mm, and greater than 200 mm). Failed patency was defined as recurrence of symptoms with a decline in ankle brachial index, or stenosis identified by duplex ultrasound, or reintervention. Results: Compared to lesions less than 100 mm, longer lesions had higher failed primary patency (100-200 mm: HR = 2.0, P = 0.16, >200 mm: HR = 2.6, P = 0.03). Failed secondary patency was similar for short and intermediate lesions (< 5% incidence), but trended higher for lesions >200 mm (HR = 4.2, P = 0.06). An initial procedure residual stenosis greater than 20% was the only significant multivariable factor related to poorer long-term patency (HR = 15.8, P = 0.003). Compared to short lesions, the gain in long-term patency with out-patient surveillance and reintervention was higher for longer lesions and significantly so for intermediate lesions (100-200 mm = 23% versus <100 mm = 8%, P = 0.041). Conclusion: Percutaneous treatment of long femoral artery lesions can provide acceptable long-term patency for patients with claudication when out-patient surveillance is used to identify patients who require repeat interventions. Future long-term studies should consider overall patency encompassing more than one percutaneous reintervention. (C) 2011 Wiley-Liss, Inc. C1 [Connors, Gerard; Todoran, Thomas M.; Kinlay, Scott] VA Boston Healthcare Syst, Div Cardiovasc, W Roxbury, MA 02132 USA. [Connors, Gerard; Todoran, Thomas M.; Engelson, Brian A.; Sobieszczyk, Piotr S.; Eisenhauer, Andrew C.; Kinlay, Scott] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Connors, Gerard; Todoran, Thomas M.; Sobieszczyk, Piotr S.; Eisenhauer, Andrew C.; Kinlay, Scott] Harvard Univ, Sch Med, Boston, MA USA. RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Div Cardiovasc, W Roxbury, MA 02132 USA. EM scott.kinlay@va.gov NR 33 TC 13 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN 1 PY 2011 VL 77 IS 7 BP 1055 EP 1062 DI 10.1002/ccd.22802 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 767MT UT WOS:000290861400027 PM 20853355 ER PT J AU Mohamed, JA DuPont, HL Flores, J Palur, H Nair, P Jiang, ZD Guo, DC Belkind-Gerson, J Okhuysen, PC AF Mohamed, Jamal A. DuPont, Herbert L. Flores, Jose Palur, Himaja Nair, Parvathy Jiang, Zhi-Dong Guo, Dongchuan Belkind-Gerson, Jaime Okhuysen, Pablo C. TI Single Nucleotide Polymorphisms in the Promoter of the Gene Encoding the Lipopolysaccharide Receptor CD14 Are Associated With Bacterial Diarrhea in US and Canadian Travelers to Mexico SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PATTERN-RECOGNITION RECEPTOR; ENTEROTOXIGENIC ESCHERICHIA-COLI; NORTH-AMERICAN TRAVELERS; SOLUBLE CD14; DEVELOPING-COUNTRIES; HELICOBACTER-PYLORI; INFECTION; ENDOTOXIN; ANTIBODY; DISEASE AB Background. Under normal conditions, the expression of CD14, which is the principal receptor for bacterial lipopolysaccharide, is down-regulated in the intestinal mucosa but increases in response to inflammatory stimuli. The aim of the present study was to investigate whether fecal CD14 levels increased in response to infection with diarrheagenic Escherichia coli and whether single nucleotide polymorphisms (SNPs) in the CD14 gene were associated with an increased susceptibility to traveler's diarrhea (TD) in US visitors to Mexico. Methods. Six SNPs located at the promoter, exon, and untranslated regions of CD14 were typed in a prospective cohort study of 1360 visitors to Mexico at risk for TD. Stools from visitors with TD were studied for enteric pathogens by culture, colony hybridization, and polymerase chain reaction. Fecal soluble CD14 (sCD14) was measured in a subgroup of 203 adults with diarrhea and 66 healthy controls by enzyme-linked immunosorbent assay. Results. The minor allele frequencies for CD14 SNPs were significantly different among the various racial and ethnic groups studied. Two SNPs in the promoter region of CD14 (-159 C > T; rs2569190 and -4191 C > T; rs5744441) were found to be associated with TD in White visitors. The -159 TT genotype was associated with a higher risk for TD (Relative risk [RR], 1.21; 95% confidence interval [CI], 1.05-1.38; P = .008), whereas individuals with the -4191 TT genotype were protected from infection (RR, 0.82; 95% CI, 0.71-0.92; P = .006). Subjects with TD excreted higher levels of fecal CD14 than did healthy controls (33,480 pg/mL vs 6178 pg/mL; P < .02). Fecal sCD14 levels were higher in stool samples from visitors with TD and the -159 TT genotype than they were in visitors with the CC/CT genotypes (P = .02), and stool samples from subjects with the -4191 CC genotype had higher fecal sCD14 levels than did stool samples from visitors with the CT/TT (P = .005) genotype. In a multivariate analysis with haplotypes constructed with the 6 SNPs studied, subjects with the haplotype containing the -159 C and the -4191 T allele were less likely to acquire TD (P = .015). Conclusions. Our study suggests that CD14 levels increase in response to bacterial diarrhea and that polymorphisms in the CD14 gene influence susceptibility to TD. Intestinal CD14 plays an important role in the innate immune response to enteric pathogens. C1 [Mohamed, Jamal A.; DuPont, Herbert L.; Flores, Jose; Palur, Himaja; Nair, Parvathy; Okhuysen, Pablo C.] Univ Texas Med Sch Houston, Div Infect Dis, Dept Internal Med, Houston, TX 77030 USA. [DuPont, Herbert L.; Jiang, Zhi-Dong; Okhuysen, Pablo C.] Univ Texas Sch Publ Hlth Houston, Ctr Infect Dis, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. [DuPont, Herbert L.; Okhuysen, Pablo C.] Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. [DuPont, Herbert L.] St Lukes Episcopal Hosp, Houston, TX 77030 USA. [Guo, Dongchuan] Div Med Genet UT Hlth, Dept Internal Med, Houston, TX USA. [Belkind-Gerson, Jaime] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Okhuysen, PC (reprint author), Univ Texas Med Sch Houston, Div Infect Dis, Dept Internal Med, 6431 Fannin St,MSB 2-112, Houston, TX 77030 USA. EM pablo.c.okhuysen@uth.tmc.edu OI Okhuysen, Pablo/0000-0002-1596-3411 FU National Institutes of Health [R01 AI54948-01]; University of Texas Center for Clinical and Translational Sciences of the University of Texas Medical School at Houston [UL1RR024148]; Salix Pharmaceuticals; Pfizer; Cubist; Theravance; [DK56338] FX This work was supported by the National Institutes of Health (R01 AI54948-01 to P. C. O.), the University of Texas Center for Clinical and Translational Sciences (UL1RR024148) of the University of Texas Medical School at Houston, and DK56338, which funds the Texas Gulf Coast Digestive Diseases Center.; P. C. O. has received payments for lectures and speakers' bureau from Salix Pharmaceuticals, Pfizer, Cubist, and Theravance and has received payment through his institution for consultation work with Intercell unrelated to this article. All other authors: no conflicts. NR 47 TC 14 Z9 14 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2011 VL 52 IS 11 BP 1332 EP 1341 DI 10.1093/cid/cir228 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 767JZ UT WOS:000290854200008 PM 21596674 ER PT J AU Mayer, KH Mimiaga, MJ AF Mayer, Kenneth H. Mimiaga, Matthew J. TI Past as Prologue: The Refractory and Evolving HIV Epidemic Among Men Who Have Sex With Men SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID ACTIVE ANTIRETROVIRAL THERAPY; VIRUS TYPE-III; HOMOSEXUAL-MEN; RISK BEHAVIOR; BISEXUAL MEN; SAN-FRANCISCO; UNITED-STATES; HTLV-III; INFECTION; GAY C1 [Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Mayer, Kenneth H.; Mimiaga, Matthew J.] Brown Univ, Miriam Hosp, Warren Alpert Med Sch, Providence, RI USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Mayer, KH (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St, Boston, MA 02215 USA. EM kenneth_mayer@brown.edu NR 38 TC 5 Z9 5 U1 2 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2011 VL 52 IS 11 BP 1371 EP 1373 DI 10.1093/cid/cir206 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 767JZ UT WOS:000290854200014 PM 21596679 ER PT J AU McDonald, J Goldman, RE O'Brien, A Ayash, C Mitchell, K Marshall, R Simon, SR Taveras, EM AF McDonald, Julia Goldman, Roberta E. O'Brien, Ashley Ayash, Christine Mitchell, Kathy Marshall, Richard Simon, Steven R. Taveras, Elsie M. TI Health Information Technology to Guide Pediatric Obesity Management SO CLINICAL PEDIATRICS LA English DT Article DE obesity treatment; pediatric; guidelines; electronic records; decision support system ID ELECTRONIC MEDICAL-RECORD; CHILDHOOD OBESITY; CARE; RECOMMENDATIONS; TRIAL AB The purpose of this study was to examine pediatricians' familiarity with expert committee recommendations on the management of childhood obesity and their use of health information technology for obesity-related care. The authors interviewed 35 pediatricians from 17 primary care practices using an electronic health record; immersion crystallization facilitated analysis of the qualitative data. Nearly all pediatricians were unfamiliar with expert recommendations; however, all participants reported using growth charts and providing nutrition and physical activity counseling. Most participants wanted easy access to educational materials they could print for patients. The majority of participants were in favor of an electronic alert to identify obese patients, remind clinicians of current guidelines, and facilitate ordering, believing it would help standardize care. Concerns included "alert fatigue," distraction, and disruption of workflow. Suggestions for future electronic functions included tailored educational materials and physical activity resources customized by patient address. C1 [McDonald, Julia] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [McDonald, Julia; O'Brien, Ashley; Ayash, Christine; Taveras, Elsie M.] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Goldman, Roberta E.] Brown Univ, Providence, RI 02912 USA. [Goldman, Roberta E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Mitchell, Kathy; Marshall, Richard] Harvard Vanguard Med Associates, Boston, MA USA. [Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP McDonald, J (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,3rd Floor, Boston, MA 02215 USA. EM Julia_mcdonald@hphc.org FU American Diabetes Association; Robert Wood Johnson Foundation; U.S. Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation FX The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article:; This study was supported in part by grants from the American Diabetes Association, the Robert Wood Johnson Foundation, and the U.S. Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation. The opinions and conclusions expressed herein are solely those of the author(s) and should not be constructed as representing the opinions or policy of any agency of the Federal Government. NR 17 TC 8 Z9 8 U1 2 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD JUN PY 2011 VL 50 IS 6 BP 543 EP 549 DI 10.1177/0009922810395131 PG 7 WC Pediatrics SC Pediatrics GA 763US UT WOS:000290585800011 PM 21565885 ER PT J AU Pelosi, P Ferguson, ND Frutos-Vivar, F Anzueto, A Putensen, C Raymondos, K Apezteguia, C Desmery, P Hurtado, J Abroug, F Elizalde, J Tomicic, V Cakar, N Gonzalez, M Arabi, Y Moreno, R Esteban, A AF Pelosi, Paolo Ferguson, Niall D. Frutos-Vivar, Fernando Anzueto, Antonio Putensen, Christian Raymondos, Konstantinos Apezteguia, Carlos Desmery, Pablo Hurtado, Javier Abroug, Fekri Elizalde, Jose Tomicic, Vinko Cakar, Nahit Gonzalez, Marco Arabi, Yaseen Moreno, Rui Esteban, Andres CA Ventila Study Grp TI Management and outcome of mechanically ventilated neurologic patients SO CRITICAL CARE MEDICINE LA English DT Article DE mechanical ventilation; stroke; brain trauma; outcome; mortality; epidemiology ID TRAUMATIC BRAIN-INJURY; ACUTE LUNG INJURY; ANEURYSMAL SUBARACHNOID HEMORRHAGE; RESPIRATORY-DISTRESS-SYNDROME; INTENSIVE-CARE-UNIT; SEVERE HEAD-INJURY; EXTRACRANIAL COMPLICATIONS; INTRACEREBRAL HEMORRHAGE; MEDICAL COMPLICATIONS; ORGAN DYSFUNCTION AB Objective: To describe and compare characteristics, ventilatory practices, and associated outcomes among mechanically ventilated patients with different types of brain injury and between neurologic and nonneurologic patients. Design: Secondary analysis of a prospective, observational, and multicenter study on mechanical ventilation. Setting: Three hundred forty-nine intensive care units from 23 countries. Patients: We included 552 mechanically ventilated neurologic patients (362 patients with stroke and 190 patients with brain trauma). For comparison we used a control group of 4,030 mixed patients who were ventilated for nonneurologic reasons. Interventions: None. Measurements and Main Results: We collected demographics, ventilatory settings, organ failures, and complications arising during ventilation and outcomes. Multivariate logistic regression analysis was performed with intensive care unit mortality as the dependent variable. At admission, a Glasgow Coma Scale score <= 8 was observed in 68% of the stroke, 77% of the brain trauma, and 29% of the nonneurologic patients. Modes of ventilation and use of a lung-protective strategy within the first week of mechanical ventilation were similar between groups. In comparison with nonneurologic patients, patients with neurologic disease developed fewer complications over the course of mechanical ventilation with the exception of a higher rate of ventilator-associated pneumonia in the brain trauma cohort. Neurologic patients showed higher rates of tracheotomy and longer duration of mechanical ventilation. Mortality in the intensive care unit was significantly (p <.001) higher in patients with stroke (45%) than in brain trauma (29%) and nonneurologic disease (30%). Factors associated with mortality were: stroke (in comparison to brain trauma), Glasgow Coma Scale score on day 1, and severity at admission in the intensive care unit. Conclusions: In our study, one of every five mechanically ventilated patients received this therapy as a result of a neurologic disease. This cohort of patients showed a higher mortality rate than nonneurologic patients despite a lower incidence of extracerebral organ dysfunction. (Crit Care Med 2011; 39: 1482-1492) C1 [Pelosi, Paolo] Univ Genoa, Dipartimento Sci Chirurg Diagnost Integrate, Genoa, Italy. [Ferguson, Niall D.] Univ Hlth Network, Interdept Div Crit Care Med, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Hlth Network, Dept Med, Div Respirol, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Frutos-Vivar, Fernando; Esteban, Andres] Hosp Univ Getafe, Madrid, Spain. [Frutos-Vivar, Fernando; Esteban, Andres] CIBER Enfermedades Resp, Madrid, Spain. [Anzueto, Antonio] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Putensen, Christian] Univ Bonn, Dept Anesthesiol & Intens Care Med, D-5300 Bonn, Germany. [Raymondos, Konstantinos] Hannover Med Sch, D-30623 Hannover, Germany. [Apezteguia, Carlos] Hosp Prof A Posadas, Buenos Aires, DF, Argentina. [Desmery, Pablo] Sanat Mitre, Buenos Aires, DF, Argentina. [Hurtado, Javier] Hosp Clin Montevideo, Montevideo, Uruguay. [Elizalde, Jose] Hosp ABC, Mexico City, DF, Mexico. [Tomicic, Vinko] Clin Las Lilas, Santiago, Chile. [Cakar, Nahit] Istanbul Fac Med, Istanbul, Turkey. [Gonzalez, Marco] Clin Medellin, Medellin, Colombia. [Gonzalez, Marco] Univ Pontificia Bolivariana, Medellin, Colombia. [Arabi, Yaseen] King Abdul Aziz Med City, Riyadh, Saudi Arabia. [Moreno, Rui] Hosp Santo Antonio Capuchos, Lisbon, Portugal. RP Pelosi, P (reprint author), Univ Genoa, Dipartimento Sci Chirurg Diagnost Integrate, Genoa, Italy. EM aesteban@ucigetafe.com RI Pesenti, Antonio/H-7483-2012; koca, ugur/F-1265-2016; Malbrain, Manu/B-3680-2017; OI koca, ugur/0000-0002-2949-4265; Malbrain, Manu/0000-0002-1816-5255; Severgnini, Paolo/0000-0001-8027-0059; Frutos-Vivar, Fernando/0000-0002-4648-9636; Ost, David/0000-0001-6351-5552; Ferguson, Niall/0000-0002-6213-5264; CHIUMELLO, DAVIDE ALBERTO/0000-0001-9260-3930 FU CIBER; Instituto de Salud Carlos III, Spain; Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada) FX Funded by CIBER Enfermedades Respiratorias from Instituto de Salud Carlos III, Spain.; N.D.F. is supported by a Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada). The remaining authors have not disclosed any potential conflicts of interest. NR 43 TC 34 Z9 38 U1 0 U2 6 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 JUN PY 2011 VL 39 IS 6 BP 1482 EP 1492 DI 10.1097/CCM.0b013e31821209a8 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 765NM UT WOS:000290715000036 PM 21378554 ER PT J AU Telander, DG Morales, SA Mareninov, S Forward, K Gordon, LK AF Telander, David G. Morales, Shawn A. Mareninov, Sergey Forward, Krisztina Gordon, Lynn K. TI Epithelial Membrane Protein-2 (EMP2) and Experimental Proliferative Vitreoretinopathy (PVR) SO CURRENT EYE RESEARCH LA English DT Article DE Epithelial membrane protein 2; Fibrosis; Integrin regulation; Proliferative vitreoretinopathy; Retina; Rhegmatogenous retinal detachment; Retinal pigment epithelium; Therapy; Vitreous membranes ID EXPERIMENTAL RETINAL-DETACHMENT; COLLAGEN GEL CONTRACTION; MESENCHYMAL TRANSITION; SURFACE EXPRESSION; EXPERIMENTAL-MODEL; CELL-DEATH; PATHWAY; ALKYLPHOSPHOCHOLINES; ACTIVATION; SILICONE AB Purpose: Proliferative vitreoretinopathy (PVR) is believed to result in part from de-differentiation of retinal pigment epithelium (RPE) with cellular migration in the vitreous cavity, membrane formation, and contraction in an aberrant wound-healing strategy. In an in vitro collagen-gel contraction assay, epithelial membrane protein 2 (EMP2) controls contraction through activation of focal adhesion kinase (FAK) in a RPE cell line (ARPE-19). The purpose of this study was to investigate how blocking or altering the level of EMP2 expression changed clinical PVR in an in vivo model. Methods: Using the ARPE-19 cell line, the levels of EMP2 modulated through stable transfections of an EMP2 overexpressing construct, EMP2 ribozyme, or vector alone. These transfected cell lines were used in a rabbit model of PVR. The severity of PVR was classified by two masked observers. An EMP2 blocking antibody was also used to decrease functional EMP2 in the PVR model. Immunohistochemistry was used to evaluate EMP2 expression in vivo. Results: The transfectants with lower levels of EMP2 had significantly less PVR severity than the degree of PVR induced by wild-type cells (p = 0.05). Also, the transfectants with a low-level of EMP2 expression showed a strong trend of less PVR severity than the high-levels EMP2 transfectants (p = 0.06). Blocking EMP2 with a specific polyclonal antibody significantly decreased the level of PVR severity (p = 0.02). PVR membranes were found to be positive for EMP2 expression. Conclusions: These in vivo studies support a direct correlation between EMP2 expression and severity of PVR. These results validate the potential for controlling RPE biology through a change in EMP2 expression, and provide a potential therapeutic target for this disease. C1 [Telander, David G.; Forward, Krisztina] Univ Calif Davis, Dept Ophthalmol, Sacramento, CA 95817 USA. [Morales, Shawn A.; Gordon, Lynn K.] Univ Calif Los Angeles, Jules Stein Eye Inst, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Mareninov, Sergey] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] Greater Los Angeles VA Healthcare syst, Los Angeles, CA USA. RP Telander, DG (reprint author), UC Davis, Retina Div, Dept Ophthalmol & Visual Sci, 4860 Y St,Suite 2400, Sacramento, CA 95817 USA. EM dgtelander@ucdavis.edu FU Research to Prevent Blindness; Foundation Fighting Blindness; Veterans Administration; NIH NEI [1R01EY019909-01A1] FX The authors acknowledge support via unrestricted departmental funds from Research to Prevent Blindness, Foundation Fighting Blindness (DGT), and a Veterans Administration Merit Grant (LKG). NIH NEI R01 Grant Number: 1R01EY019909-01A1. NR 34 TC 8 Z9 8 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUN PY 2011 VL 36 IS 6 BP 546 EP 552 DI 10.3109/02713683.2011.561468 PG 7 WC Ophthalmology SC Ophthalmology GA 765SE UT WOS:000290728100008 PM 21591864 ER PT J AU Signorovitch, JE Wu, EQ Betts, KA Parikh, K Kantor, E Guo, A Bollu, VK Williams, D Wei, LJ DeAngelo, DJ AF Signorovitch, James E. Wu, Eric Q. Betts, Keith A. Parikh, Kejal Kantor, Evan Guo, Amy Bollu, Vamsi K. Williams, Denise Wei, L. J. DeAngelo, Daniel J. TI Comparative efficacy of nilotinib and dasatinib in newly diagnosed chronic myeloid leukemia: a matching-adjusted indirect comparison of randomized trials SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE CML; Nilotinib; Dasatinib; Efficacy; Matching-adjusted indirect comparison ID CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; LOW-DOSE CYTARABINE; MOLECULAR RESPONSES; IMATINIB MESYLATE; INTERFERON AB Objective: Nilotinib and dasatinib have not been directly compared in a randomized trial for the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP). The purpose of this study was to indirectly compare rates of major molecular response (MMR), progression-free survival (PFS) and overall survival by month 12 with nilotinib and dasatinib treatment of newly diagnosed CML-CP. Methods: Individual patient data from a randomized trial of nilotinib vs. imatinib (ENESTnd) and published summary data from a separate randomized trial of dasatinib vs. imatinib (DASISION) were utilized. A matching-adjusted indirect comparison was conducted by weighting individual patients treated with nilotinib to match baseline characteristics reported for dasatinib-treated patients, including age, gender, ECOG performance status and hematology lab values. After matching, efficacy outcomes were compared for patients treated with nilotinib 300 mg twice daily vs. dasatinib 100 mg once daily. Patients randomized to imatinib 400 mg once daily in each trial were used to assess the adequacy of the matching. Results: Before matching, patients randomized to nilotinib in ENESTnd (n = 273) were older, with a lower median platelet count and more favorable performance status compared to patients randomized to dasatinib in DASISION (n = 259). After matching, all baseline characteristics were balanced across treatment groups. Matched patients treated with nilotinib vs. dasatinib experienced significantly higher rates of MMR (56.8 vs. 45.9%, p = 0.014) and overall survival (99.5 vs. 97.3%, p = 0.046) and numerically higher rates of PFS (98.8 vs. 96.5%). Matched imatinib arms showed no statistically significant or clinically meaningful differences in these outcomes. Limitations: Baseline measures unavailable in one or both trials could not be matched. Adverse event rates were not formally compared across trials due to differences in reporting. Conclusion: Nilotinib was associated with significantly higher rates of MMR and overall survival compared with dasatinib by month 12 in the treatment of newly diagnosed CML-CP. C1 [Signorovitch, James E.; Wu, Eric Q.; Betts, Keith A.; Parikh, Kejal; Kantor, Evan] Anal Grp Inc, Boston, MA 02199 USA. [Guo, Amy; Bollu, Vamsi K.; Williams, Denise] Novartis Pharmaceut, E Hanover, NJ USA. [Wei, L. J.] Harvard Univ, Boston, MA 02115 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Signorovitch, JE (reprint author), Anal Grp Inc, 111 Huntington Ave,10th Floor, Boston, MA 02199 USA. EM jsignorovitch@analysisgroup.com OI Betts, Keith/0000-0002-3088-7453 FU Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; Novartis Pharmaceuticals Corporation FX Research was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.; J.E.S., E. Q. W., K. A. B., K. P. and E. K. have disclosed that they are employees of Analysis Group, Inc., a company that received funding from Novartis Pharmaceuticals Corporation to conduct this study. A. G., V. K. B. and D. W. have disclosed that they are employees of Novartis Pharmaceuticals Corporation. D.J.D. is a member of a scientific advisory board with Novartis. L.J.W. is on various Data Monitoring Boards for Novartis clinical studies and is a statistical consultant for Novartis. He is also a consultant for Merck, J&J, GSK, Amgen, Roche, Pfizer, Alkermes and Genzyme. NR 18 TC 20 Z9 22 U1 2 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD JUN PY 2011 VL 27 IS 6 BP 1263 EP 1271 DI 10.1185/03007995.2011.576238 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 764YY UT WOS:000290671800019 PM 21524239 ER PT J AU Song, C Milbury, CA Li, J Liu, PF Zhao, MP Makrigiorgos, GM AF Song, Chen Milbury, Coren A. Li, Jin Liu, Pingfang Zhao, Meiping Makrigiorgos, Gerasimos Mike TI Rapid and Sensitive Detection of KRAS Mutation After fast-COLD-PCR Enrichment and High-resolution Melting Analysis SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE COLD-PCR; HRM; KRAS; lung adenocarcinoma; mutation detection ID CELL LUNG-CANCER; COLORECTAL-CANCER; SIGNAL GENERATION; SOMATIC MUTATION; RAS MUTATIONS; DNA; HETEROGENEITY; EGFR; IDENTIFICATION; METASTASES AB KRAS mutations exhibit significant predictive and prognostic value in cancer. Efficient, sensitive, and accurate molecular approaches are required to evaluate KRAS mutation status, even when mutant alleles are restricted to a small portion of a clinical sample, which otherwise contains wild-type alleles. We describe a highly sensitive method to detect KRAS mutations by high-resolution melting (HRM) analysis after mutation enrichment by fast-COLDpolymerase chain reaction (PCR). Using 10 ng of starting DNA and after fast-COLD-PCR of a 76-bp region containing KRAS codons 12 and 13; the amplicons undergo a nested conventional PCR reaction followed by HRM analysis. Samples exhibiting aberrant melting profiles are sequenced to identify mutation type and position. Serial dilution experiments indicate a sensitivity of approximately 0.3% mutant-to-wild type for HRM-based mutation detection and the ability to directly sequence mutation-containing samples. A number of lung adenocarcinoma specimens earlier characterized were screened. Fast-COLD-PCR-HRM analysis correctly identified KRAS mutations and also showed a previously undetected, low-level missense GGT > TTT complex mutation. On account of the short target regions and low requirement of starting DNA, this rapid, cost-effective, and sensitive fast-COLD-PCR-HRM approach is expected to find broad application for detecting low-abundance KRAS mutations in a wide range of clinical specimens. C1 [Song, Chen; Milbury, Coren A.; Li, Jin; Liu, Pingfang; Makrigiorgos, Gerasimos Mike] Harvard Univ, Brigham & Womens Hosp, WDivis Genome Stabil & DNA Repair, Dana Farber Brigham & Womens Canc Ctr,Sch Med, Boston, MA 02115 USA. [Song, Chen; Milbury, Coren A.; Li, Jin; Liu, Pingfang; Makrigiorgos, Gerasimos Mike] Harvard Univ, Sch Med, Dept Radiat Oncol, Div Med Phys & Biophys, Boston, MA 02115 USA. [Song, Chen; Zhao, Meiping] Peking Univ, Coll Chem & Mol Engn, Minist Educ, BNLMS,Key Lab Bioorgan Chem & Mol Engn, Beijing 100871, Peoples R China. RP Makrigiorgos, GM (reprint author), Harvard Univ, Brigham & Womens Hosp, WDivis Genome Stabil & DNA Repair, Dana Farber Brigham & Womens Canc Ctr,Sch Med, Level L2,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org RI Song, Chen/H-6615-2015 OI Song, Chen/0000-0002-4439-4377 FU NCI [T32-CA009078]; China Scholarship Council CSC [2009601213]; JCRT Foundation; NIH [CA-138280, CA-111994] FX Supported by T32-CA009078 from the NCI (C. M.), by a student grant from the China Scholarship Council CSC 2009601213 (C. S.), by the JCRT Foundation (J.L.), and by NIH grants CA-138280 and CA-111994. The contents of this study are the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 44 TC 14 Z9 17 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD JUN PY 2011 VL 20 IS 2 BP 81 EP 89 DI 10.1097/PDM.0b013e3181fde92f PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 764VI UT WOS:000290662100003 PM 21532494 ER PT J AU Jacobson, BC Giovannucci, EL Fuchs, CS AF Jacobson, Brian C. Giovannucci, Edward L. Fuchs, Charles S. TI Smoking and Barrett's Esophagus in Women Who Undergo Upper Endoscopy SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Barrett's esophagus; Smoking; Cigarettes; Gastroesophageal reflux; GERD ID GASTROESOPHAGEAL-REFLUX DISEASE; BODY-MASS INDEX; RISK-FACTORS; GASTRIC CARDIA; CIGARETTE-SMOKING; UNITED-STATES; ESOPHAGOGASTRIC JUNCTION; INCREASING INCIDENCE; GENERAL-POPULATION; CANCER-RISK AB Background Cigarette use is associated with esophageal adenocarcinoma, and cross-sectional studies suggest an association between smoking and Barrett's esophagus. Aims We sought to examine prospectively the effect of smoking on the risk for Barrett's esophagus. Methods This was a prospective cohort study among 20,863 women within the Nurses' Health Study who underwent upper gastrointestinal endoscopy for any reason between 1980 and 2006. We assessed the association between smoking and pathologically-confirmed Barrett's esophagus (n = 377). Self-reported data on smoking and potential confounding variables were collected from biennial questionnaires. Results Compared with women who never smoked, former smokers of 1-24 cigarettes/day had a multivariate odds ratio for Barrett's esophagus of 1.25 (95% CI 0.99-1.59), former smokers of a parts per thousand yen25 cigarettes/day had a multivariate odds ratio of 1.52 (95% CI 1.04-2.22), current smokers of 1-24 cigarettes/day had a multivariate odds ratio of 0.89 (95% CI 0.54-1.45), and current smokers of a parts per thousand yen25 cigarettes/day had a multivariate odds ratio of 0.92 (95% CI 0.34-2.54). The risk for Barrett's esophagus increased significantly with increasing pack-years smoked among former (P = 0.008) but not current smokers (P = 0.99), especially when considering exposure a parts per thousand yen25 years before index endoscopy. Results were similar among women reporting regular heartburn/acid-reflux one or more times a week, and were not accounted for by changes in weight. Conclusions Heavy, remote smoking is associated with an increased risk for Barrett's esophagus. This finding suggests a long latency period between exposure and development of the disease, even after discontinuation of smoking. C1 [Jacobson, Brian C.] Boston Univ, Med Ctr, Dept Med, Gastroenterol Sect, Boston, MA 02118 USA. [Jacobson, Brian C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber & Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Giovannucci, Edward L.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. RP Jacobson, BC (reprint author), Boston Univ, Med Ctr, Dept Med, Gastroenterol Sect, 85 E Concord St,Room 7721, Boston, MA 02118 USA. EM brian.jacobson@bmc.org OI Jacobson, Brian/0000-0001-7064-2357 FU National Cancer Institute [CA087969]; National Institutes of Diabetes and Digestive and Kidney Diseases [RO1DK088782] FX The Nurses' Health Study is funded by the National Cancer Institute program project grant CA087969. Dr Jacobson was funded by a grant from the National Institutes of Diabetes and Digestive and Kidney Diseases (RO1DK088782). None of the authors has any other financial disclosures. NR 73 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 2011 VL 56 IS 6 BP 1707 EP 1717 DI 10.1007/s10620-011-1672-4 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 766HF UT WOS:000290770900017 PM 21448698 ER PT J AU Michalek, W Semler, JR Kuo, B AF Michalek, Whitney Semler, John R. Kuo, Braden TI Impact of Acid Suppression on Upper Gastrointestinal pH and Motility SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Stomach and duodenum; Gastric emptying; Motility; Acidity (intragastric) ID GASTROESOPHAGEAL-REFLUX DISEASE; HEIDELBERG CAPSULE; SCINTIGRAPHY; PANTOPRAZOLE; OMEPRAZOLE; THERAPY; TRANSIT; HEALTHY AB Background Proton pump inhibitors (PPIs), widely prescribed to patients with upper gastrointestinal symptoms, alter intragastric pH, and may affect upper gastrointestinal transit and motility parameters in addition to affecting the ability to determine Wireless Motility Capsule (WMC) gastric emptying time. Aim To assess PPI effect on motility parameters of the upper gastrointestinal tract and to determine if PPIs confound ability of WMC to measure gastric emptying time. Methods Twenty healthy subjects were treated with esomeprazole 40 mg bid for 1 week. Another 50 healthy subjects underwent evaluation in absence of PPIs. All subjects underwent WMC test after meal ingestion. After a rapid, sustained luminal pH rise a parts per thousand yen 0.5 pH units, marking potential gastric emptying time of WMC, an abdominal X-ray (KUB) was taken for gastric emptying time confirmation. Mean pH, pressure and transit time were compared between PPI-treated and untreated groups. Results There was no difference in gastric emptying time, small bowel transit time (SBTT), or pressure profiles between the groups. The pH in all cases rose a parts per thousand yen 0.5 pH units. Distal small bowel pH was significantly lower in subjects on PPIs. Gastric emptying time was identified in all subjects treated with PPIs. Pressure and slope criteria were developed to confirm the time of emptying. Conclusion PPI therapy does not have a significant impact on upper gastrointestinal transit and motility but it does decrease distal small bowel pH. The medication reduced the magnitude of pH change at gastric emptying time but using additional criteria based on slope and contraction frequency, WMC was able to measure gastric emptying time in all patients treated with PPIs. C1 [Michalek, Whitney; Kuo, Braden] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Semler, John R.] SmartPill Corp, Buffalo, NY 14203 USA. RP Kuo, B (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ 274, Boston, MA 02114 USA. EM wmichalek@partners.org; jrsemeler@smartpillcorp.com; bkuo@partners.org FU The Smart Pill Corporation [208598]; National Institute of Health [218969]; International Foundation for Functional Gastrointestinal Disorders FX This study was funded in part by The Smart Pill Corporation, grant number 208598, also in part by the National Institute of Health, grant number 218969, and International Foundation for Functional Gastrointestinal Disorders. NR 22 TC 16 Z9 17 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 2011 VL 56 IS 6 BP 1735 EP 1742 DI 10.1007/s10620-010-1479-8 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 766HF UT WOS:000290770900021 PM 21086166 ER PT J AU Jessup, JA Zhang, LL Presley, TD Kim-Shapiro, DB Wang, H Chen, AF Groban, L AF Jessup, Jewell A. Zhang, Lili Presley, Tennille D. Kim-Shapiro, Daniel B. Wang, Hao Chen, Alex F. Groban, Leanne TI Tetrahydrobiopterin Restores Diastolic Function and Attenuates Superoxide Production in Ovariectomized mRen2.Lewis Rats SO ENDOCRINOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; PREVENTS ENDOTHELIAL DYSFUNCTION; MYOCARDIAL REPERFUSION INJURY; LEFT-VENTRICULAR HYPERTROPHY; ESTROGEN-RECEPTOR SUBTYPES; HEART-FAILURE; OXIDATIVE STRESS; 17-BETA-ESTRADIOL ANTAGONIZES; VASCULAR TETRAHYDROBIOPTERIN; POSTMENOPAUSAL WOMEN AB After oophorectomy, mRen2.Lewis rats exhibit diastolic dysfunction associated with elevated superoxide, increased cardiac neuronal nitric oxide synthase (nNOS) expression, and diminished myocardial tetrahydrobiopterin (BH4) content, effects that are attenuated with selective nNOS inhibition. BH4 is an essential cofactor of nNOS catalytic activity leading to nitric oxide production. Therefore, we assessed the effect of 4wk BH4 supplementation on diastolic function and left ventricular (LV) remodeling in oophorectomized mRen2.Lewis rats compared with sham-operated controls. Female mRen2.Lewis rats underwent either bilateral ovariectomy (OVX) (n = 19) or sham operation (n = 13) at 4wk of age. Beginning at 11 wk of age, OVX rats were randomized to receive either BH4 (10 mg/kg.d) or saline, whereas the sham rats received saline via sc mini-pumps. Loss of ovarian hormones reduced cardiac BH4 when compared with control hearts; this was associated with impaired myocardial relaxation, augmented filling pressures, increased collagen deposition, and thickened LV walls. Additionally, superoxide production increased and nitric oxide decreased in hearts from OVX compared with sham rats. Chronic BH4 supplementation after OVX improved diastolic function and attenuated LV remodeling while restoring myocardial nitric oxide release and preventing reactive oxygen species generation. These data indicate that BH4 supplementation protects against the adverse effects of ovarian hormonal loss on diastolic function and cardiac structure in mRen2.Lewis rats by restoring myocardial NO release and mitigating myocardial O-2(-) generation. Whether BH4 supplementation is a therapeutic option for the management of diastolic dysfunction in postmenopausal women will require direct testing in humans. (Endocrinology 152: 2428-2436, 2011) C1 [Wang, Hao; Groban, Leanne] Wake Forest Univ, Dept Anesthesiol, Sch Med, Winston Salem, NC 27157 USA. [Jessup, Jewell A.; Groban, Leanne] Wake Forest Univ, Dept Physiol, Sch Med, Winston Salem, NC 27157 USA. [Jessup, Jewell A.; Groban, Leanne] Wake Forest Univ, Dept Pharmacol, Sch Med, Winston Salem, NC 27157 USA. [Zhang, Lili; Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15206 USA. Vet Affairs Pittsburgh Healthcare Syst, Vasc Surg Res, Pittsburgh, PA 15206 USA. [Presley, Tennille D.; Kim-Shapiro, Daniel B.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27106 USA. [Presley, Tennille D.; Kim-Shapiro, Daniel B.] Wake Forest Univ, Translat Sci Ctr, Winston Salem, NC 27106 USA. RP Groban, L (reprint author), Wake Forest Univ, Dept Anesthesiol, Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM lgroban@wfubmc.edu FU National Institutes of Health [R01-AG033727-01, KO8-AG026764-05, HL-058091, R01 GM077352, 2PO1 HL-051952]; American Heart Association [0855601GH] FX This work was supported by grants from the National Institutes of Health R01-AG033727-01 (to L.G.), KO8-AG026764-05 Paul Beeson award (to L.G.), HL-058091 (to D.B.K.-S.), R01 GM077352 (to A.F.C.), 2PO1 HL-051952 (to C.M. Ferrario), and American Heart Association Grant-in-Aid 0855601GH (to A.F.C.). Support was limited to funding. NR 58 TC 11 Z9 12 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2011 VL 152 IS 6 BP 2428 EP 2436 DI 10.1210/en.2011-0061 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 766MY UT WOS:000290788500029 PM 21427216 ER PT J AU Kreuziger, LMB Wolanskyj, AP Hanson, CA Steensma, DP AF Kreuziger, Lisa M. Baumann Wolanskyj, Alexandra P. Hanson, Curtis A. Steensma, David P. TI Lack of efficacy of pyridoxine (vitamin B6) treatment in acquired idiopathic sideroblastic anaemia, including refractory anaemia with ring sideroblasts SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE pyridoxine; vitamin B6; sideroblastic anaemia; myelodysplastic syndrome; refractory anaemia with ring sideroblasts ID WORLD-HEALTH-ORGANIZATION; MYELODYSPLASTIC SYNDROMES; CLASSIFICATION; ANAEMIA; MUTATION AB Pyridoxine, or vitamin B6, is commonly used to treat acquired idiopathic sideroblastic anaemia (AISA, including refractory anaemia with ring sideroblasts), but the efficacy of this therapy in an unselected AISA population (i.e. patients without confirmed ALAS2 or other pyridoxine-responsive germline mutations) has not been established. We reviewed clinical data from 231 patients with AISA and found that 42% of 203 evaluable patients had been treated with pyridoxine. Only 6.8% of pyridoxine-treated patients experienced a haemoglobin improvement (>= 1.5 g/dL) meeting 2006 International Working Group for Myelodysplastic Syndromes standardised response criteria. As some patients received combination therapy with erythropoietin or other agents, improvement could be attributed to pyridoxine monotherapy in only one patient (1.4%). Smaller, less meaningful increments in haemoglobin levels of 0.5 g/dL were observed in 13.5% of patients. Response to therapy did not correlate with International Prognostic Scoring System (IPSS) risk group or multilineage vs unilineage dysplasia. New symptomatic peripheral neuropathy was noted in 2.3% of patients treated with pyridoxine. In this large series of unselected patients with sideroblastic anaemia, pyridoxine therapy was ineffective and was associated with a risk of adverse effects. Pyridoxine therapy should be reserved for patients with known or suspected pyridoxine-responsive mutations. C1 [Steensma, David P.] Harvard Univ, Dana Farber Canc Inst, Div Hematol Oncol, Sch Med, Boston, MA 02115 USA. [Kreuziger, Lisa M. Baumann; Wolanskyj, Alexandra P.; Hanson, Curtis A.] Mayo Clin, Rochester, MN USA. [Kreuziger, Lisa M. Baumann] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. RP Steensma, DP (reprint author), Harvard Univ, Dana Farber Canc Inst, Div Hematol Oncol, Sch Med, 44 Binney St,Suite D1B30, Boston, MA 02115 USA. EM David_Steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284; Baumann Kreuziger, Lisa/0000-0002-1171-0548 FU Robert A. Kyle Hematologic Malignancies Fund FX We thank Darrell Schroeder for advice regarding statistical analysis. This study was funded by a grant from the Robert A. Kyle Hematologic Malignancies Fund. NR 20 TC 2 Z9 2 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JUN PY 2011 VL 86 IS 6 BP 512 EP 516 DI 10.1111/j.1600-0609.2011.01604.x PG 5 WC Hematology SC Hematology GA 765TH UT WOS:000290731000009 ER PT J AU Benzer, JK Young, G Stolzmann, K Osatuke, K Meterko, M Caso, A White, B Mohr, DC AF Benzer, Justin K. Young, Gary Stolzmann, Kelly Osatuke, Katerine Meterko, Mark Caso, Allison White, Bert Mohr, David C. TI The Relationship between Organizational Climate and Quality of Chronic Disease Management SO HEALTH SERVICES RESEARCH LA English DT Article DE Organizational climate; primary care; diabetes; organizational context ID PRIMARY-CARE; HEALTH-CARE; CHRONIC ILLNESS; PSYCHOLOGICAL CLIMATE; GROUP-PERFORMANCE; OUTCOMES; IMPROVE; PERCEPTIONS; BEHAVIOR; INTERDEPENDENCE AB Objective To test the utility of a two-dimensional model of organizational climate for explaining variation in diabetes care between primary care clinics. Data Sources/Study Setting Secondary data were obtained from 223 primary care clinics in the Department of Veterans Affairs health care system. Study Design Organizational climate was defined using the dimensions of task and relational climate. The association between primary care organizational climate and diabetes processes and intermediate outcomes were estimated for 4,539 patients in a cross-sectional study. Data Collection/Extraction Methods All data were collected from administrative datasets. The climate data were drawn from the 2007 VA All Employee Survey, and the outcomes data were collected as part of the VA External Peer Review Program. Climate data were aggregated to the facility level of analysis and merged with patient-level data. Principal Findings Relational climate was related to an increased likelihood of diabetes care process adherence, with significant but small effects for adherence to intermediate outcomes. Task climate was generally not shown to be related to adherence. Conclusions The role of relational climate in predicting the quality of chronic care was supported. Future research should examine the mediators and moderators of relational climate and further investigate task climate. C1 [Benzer, Justin K.] VA Boston Healthcare Syst 152M, Ctr Org Leadership & Management Res COLMR, Boston, MA 02130 USA. [Young, Gary; Stolzmann, Kelly; Meterko, Mark; White, Bert; Mohr, David C.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res COLMR, Boston, MA 02130 USA. [Young, Gary] Northeastern Univ, Ctr Hlth Policy & Healthcare Res, Boston, MA 02115 USA. [Meterko, Mark; Mohr, David C.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Osatuke, Katerine] Natl Ctr Org Dev, Vet Hlth Adm, Cincinnati, OH USA. RP Benzer, JK (reprint author), VA Boston Healthcare Syst 152M, Ctr Org Leadership & Management Res COLMR, 150 S Huntington Ave, Boston, MA 02130 USA. EM justin.benzer@va.gov OI Benzer, Justin/0000-0001-5151-2127 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development [IIR 05-221]; VA Office of Academic Affiliations HSRD; Robert Wood Johnson Foundation FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (IIR 05-221). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government. Financial support was provided in part from a VA Office of Academic Affiliations HSR&D postdoctoral fellowship and a Robert Wood Johnson Foundation Investigator Award in Health Policy Research. An earlier version of this manuscript was presented at the 2010 Academy of Management Annual Meeting. The authors acknowledge the intellectual and editorial contributions of James Burgess and Mark Bauer. No conflicts of interest influenced this manuscript. Disclosures: None. Disclaimers: None. NR 60 TC 12 Z9 13 U1 4 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2011 VL 46 IS 3 BP 691 EP 711 DI 10.1111/j.1475-6773.2010.01227.x PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 758NN UT WOS:000290171600002 PM 21210799 ER PT J AU Zheng, H Zhang, W Ayanian, JZ Zaborski, LB Zaslavsky, AM AF Zheng, Hui Zhang, Wei Ayanian, John Z. Zaborski, Lawrence B. Zaslavsky, Alan M. TI Profiling Hospitals by Survival of Patients with Colorectal Cancer SO HEALTH SERVICES RESEARCH LA English DT Article DE Cancer care; colorectal cancer; provider profiling; quality measurement; Bayesian inference ID SHORT-TERM MORTALITY; RECTAL-CANCER; COLON-CANCER; QUALITY; CARE; SURGERY; PERFORMANCE; VOLUME; RATES; INFORMATION AB Objective To profile hospitals by survival rates of colorectal cancer patients in multiple periods after initial treatment. Data Sources California Cancer Registry data from 50,544 patients receiving primary surgery with curative intent for stage I-III colorectal cancer in 1994-1998, supplemented with hospital discharge abstracts. Study Design We estimated a single Bayesian hierarchical model to quantify associations of survival to 30 days, 30 days to 1 year, and 1-5 years by hospital, adjusted for patient age, sex, race, stage, tumor site, and comorbidities. We compared two profiling methods for 30-day survival and four longer-term profiling methods by the fractions of hospitals with demonstrably superior survival profiles and of hospital pairs whose relative standings could be established confidently. Principal Findings Interperiod correlation coefficients of the random effects are (95 percent credible interval 0.27, 0.85), (0.20, 0.76), and (0.19, 0.82). The three-period model ranks 5.4 percent of pairwise comparisons by 30-day survival with at least 95 percent confidence, versus 3.3 percent of pairs using a single-period model, and 15-20 percent by weighted multiperiod methods. Conclusions The quality of care for colorectal cancer provided by a hospital system is somewhat consistent across the immediate postoperative and long-term follow-up periods. Combining mortality profiles across longer periods may improve the statistical reliability of outcome comparisons. C1 [Ayanian, John Z.; Zaborski, Lawrence B.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Zheng, Hui] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Zhang, Wei] China Europe Int Business Sch, Beijing, Peoples R China. RP Zaslavsky, AM (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM zaslavsk@hcp.med.harvard.edu FU Agency for Healthcare Research and Quality [R01 HS09869, U01 CA93324]; National Cancer Institute FX This study was supported by grants R01 HS09869 and U01 CA93324 from the Agency for Healthcare Research and Quality and the National Cancer Institute. The authors are grateful to William E. Wright, Ph.D., and Mark E. Allen, M.S., for facilitating access to California Cancer Registry data; to Craig Earle, M.D., for insightful comments; and to Robert Wolf, M.S., for data preparation. NR 34 TC 6 Z9 7 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2011 VL 46 IS 3 BP 729 EP 746 DI 10.1111/j.1475-6773.2010.01222.x PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 758NN UT WOS:000290171600004 PM 21210794 ER PT J AU Boscoe, FP Schrag, D Chen, K Roohan, PJ Schymura, MJ AF Boscoe, Francis P. Schrag, Deborah Chen, Kun Roohan, Patrick J. Schymura, Maria J. TI Building Capacity to Assess Cancer Care in the Medicaid Population in New York State SO HEALTH SERVICES RESEARCH LA English DT Article DE Data linkage; cancer registration; Medicaid; economically disadvantaged populations ID SOCIOECONOMIC-STATUS; ELDERLY POPULATION; COLORECTAL-CANCER; TUMOR-REGISTRY; DISPARITIES; DIAGNOSIS; SURVIVAL; STAGE; MORTALITY AB Objective To link data from a central cancer registry with Medicaid enrollment and claims files in order to assess cancer care in an economically disadvantaged population. Data Sources Over 500,000 cancer patients diagnosed between 2002 and 2006 reported to the New York State Cancer Registry were linked with New York State Medicaid enrollment and claims records. Study Design A probabilistic linkage was performed between the two data sources. The resulting Medicaid and non-Medicaid populations were compared in terms of demographics and stage at diagnosis. Data Collection Methods Existing databases were used. Principal Findings One-quarter of cancer patients were enrolled in Medicaid at or near the time of cancer diagnosis. The Medicaid cohort was younger, more likely to be an ethnic minority, foreign born, never married, live in either an inner-city or remote rural area, and have a higher stage at diagnosis. Conclusions The linked dataset will permit detailed analysis of cancer treatment and cancer treatment disparities among historically understudied groups. The linkage has also resulted in improvements in Cancer Registry quality through the identification of errors and missing values. The linkage did present technical challenges in the form of immense file sizes not easily adaptable to desktop computers. C1 [Boscoe, Francis P.; Schymura, Maria J.] New York State Canc Registry, Menands, NY 12204 USA. [Schrag, Deborah] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. [Chen, Kun] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Roohan, Patrick J.] New York State Dept Hlth, Off Hlth Insurance Programs, Albany, NY USA. RP Boscoe, FP (reprint author), New York State Canc Registry, 150 Broadway,Suite 361, Menands, NY 12204 USA. EM fpb01@health.state.ny.us FU American Schools of Public Health/Centers for Disease Control and Prevention [S3888]; National Cancer Institute [R01-CA131847-01A1] FX This work was supported by Cooperative Agreement S3888 from the American Schools of Public Health/Centers for Disease Control and Prevention and National Cancer Institute R01-CA131847-01A1. NR 28 TC 11 Z9 12 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2011 VL 46 IS 3 BP 805 EP 820 DI 10.1111/j.1475-6773.2010.01221.x PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 758NN UT WOS:000290171600008 PM 21158856 ER PT J AU Chirinos, JA Kips, JG Roman, MJ Medina-Lezama, J Li, Y Woodiwiss, AJ Norton, GR Yasmin Van Bortel, L Wang, JG Cockcroft, JR Devereux, RB Wilkinson, IB Segers, P McEniery, CM AF Chirinos, Julio A. Kips, Jan G. Roman, Mary J. Medina-Lezama, Josefina Li, Yan Woodiwiss, Angela J. Norton, Gavin R. Yasmin Van Bortel, Luc Wang, Ji-Guang Cockcroft, John R. Devereux, Richard B. Wilkinson, Ian B. Segers, Patrick McEniery, Carmel M. TI Ethnic Differences in Arterial Wave Reflections and Normative Equations for Augmentation Index SO HYPERTENSION LA English DT Article DE wave reflections; augmentation index; ethnicity ID LEFT-VENTRICULAR HYPERTROPHY; REFERENCE VALUES; BLOOD-PRESSURE; PULSE-WAVE; CARDIOVASCULAR-DISEASE; VASCULAR-DISEASE; POPULATION; STIFFNESS; MEN; HEMODYNAMICS AB Data regarding ethnic differences in wave reflections, which markedly affect the central pressure profile, are very limited. Furthermore, because age, heart rate, and body height are strong determinants of augmentation index, relating single measurements to normative data (in which augmentation index values correspond with average population values of its determinants) is challenging. We studied subject-level data from 10 550 adults enrolled in large population-based studies. In a healthy reference sample (n = 3497), we assessed ethnic differences in augmentation index (ratio of second/first systolic peaks) and generated equations for adjusted z scores, allowing for a standardized comparison between individual augmentation index measurements and the normative population mean from subjects of the same age, sex, ethnic population, body height, and heart rate. After adjustment for age, body height, heart rate, and mean arterial pressure, African blacks (women: 154%; men: 138%) and Andean Hispanics (women: 152%; men: 133%) demonstrated higher central (aortic) augmentation index values than British whites (women: 140%; men: 128%), whereas American Indians (women: 133%; men: 122%) demonstrated lower augmentation index (all P < 0.0001), without significant differences between Chinese and British whites. Similar results were found for radial augmentation index. Nonlinear ethnic/sex-specific equations for z scores were successfully generated to adjust individual augmentation index values for age, body height, and heart rate. Marked ethnic differences in augmentation index exist, which may contribute to ethnic differences in hypertensive organ damage. Our study provides normative data that can be used to complement the interpretation of individual hemodynamic assessments among men and women of various ethnic populations, after removing the effect of various physiological determinants. (Hypertension. 2011;57:1108-1116.). Online Data Supplement C1 [Chirinos, Julio A.] Univ Penn, Div Cardiol, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Kips, Jan G.; Van Bortel, Luc; Segers, Patrick] Univ Ghent, IBiTech, B-9000 Ghent, Belgium. Univ Ghent, Heymans Inst Pharmacol, B-9000 Ghent, Belgium. [Roman, Mary J.; Devereux, Richard B.] Weill Cornell Med Coll, Div Cardiol, New York, NY USA. [Medina-Lezama, Josefina] Santa Maria Catholic Univ, Santa Maria Res Inst, Arequipa, Peru. [Li, Yan; Wang, Ji-Guang] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Hypertens, Ctr Epidemiol Studies & Clin Trials,Ruijin Hosp, Shanghai 200030, Peoples R China. [Woodiwiss, Angela J.] Univ Witwatersrand, Fac Hlth Sci, Sch Physiol, Cardiovasc Pathophysiol & Genom Res Unit, Johannesburg, South Africa. [Yasmin; Wilkinson, Ian B.; McEniery, Carmel M.] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England. [Cockcroft, John R.] Univ Cardiff, Dept Cardiol, Cardiff, S Glam, Wales. RP Chirinos, JA (reprint author), Rm 8B111,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu FU National Heart, Lung, and Blood Institute [U01-HL65521]; South African Medical Research Council; National Research Foundation of South Africa; University Research Council of the University of the Witwatersrand; Santa Maria Research Institute (AQP/Peru); National Natural Science Foundation of China [30871360, 30871081]; Ministry of Science and Technology, Beijing, China [2006BAI01A03]; Shanghai Commissions of Science and Technology [07JC14047, 06QA14043, 07ZZ32, 08SG20]; Shanghai Shenkang Hospital Development Centre [SHDC12007318]; Shanghai Jiaotong University School of Medicine; European Union [LSHM-CT-2006-037093, HEALTH-F4-2007-201550] FX This study was supported by National Heart, Lung, and Blood Institute grant U01-HL65521; the South African Medical Research Council; the National Research Foundation of South Africa; the University Research Council of the University of the Witwatersrand; the Santa Maria Research Institute (AQP/Peru); the National Natural Science Foundation of China (grants 30871360 and 30871081); the Ministry of Science and Technology (grant 2006BAI01A03), Beijing, China; the Shanghai Commissions of Science and Technology (grant 07JC14047 and the "Rising Star" program 06QA14043) and Education (grant 07ZZ32 and the "Dawn" project 08SG20); the Shanghai Shenkang Hospital Development Centre (grant SHDC12007318); Shanghai Jiaotong University School of Medicine (a grant of Distinguished Young Investigators to Y.L.); and the European Union (grants LSHM-CT-2006-037093 and HEALTH-F4-2007-201550). NR 27 TC 48 Z9 48 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 2011 VL 57 IS 6 BP 1108 EP U153 DI 10.1161/HYPERTENSIONAHA.110.166348 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 765MI UT WOS:000290710800023 PM 21536986 ER PT J AU Plourde, E Delgutte, B Brown, EN AF Plourde, Eric Delgutte, Bertrand Brown, Emery N. TI A Point Process Model for Auditory Neurons Considering Both Their Intrinsic Dynamics and the Spectrotemporal Properties of an Extrinsic Signal SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Auditory system; generalized linear model; point process; spectrotemporal receptive field; spike train model ID NEURAL SPIKING AB We propose a point process model of spiking activity from auditory neurons. The model takes account of the neuron's intrinsic dynamics as well as the spectrotemporal properties of an input stimulus. A discrete Volterra expansion is used to derive the form of the conditional intensity function. The Volterra expansion models the neuron's baseline spike rate, its intrinsic dynamics-spiking history-and the stimulus effect which in this case is the analog of the spectrotemporal receptive field (STRF). We performed the model fitting efficiently in a generalized linear model framework using ridge regression to address properly this ill-posed maximum likelihood estimation problem. The model provides an excellent fit to spiking activity from 55 auditory nerve neurons. The STRF-like representation estimated jointly with the neuron's intrinsic dynamics may offer more accurate characterizations of neural activity in the auditory system than current ones based solely on the STRF. C1 [Plourde, Eric; Brown, Emery N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Plourde, Eric; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Delgutte, Bertrand] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Delgutte, Bertrand; Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Plourde, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM eplourde@mit.edu; Bertrand_Delgutte@meei.harvard.edu; enb@neurostat.mit.edu OI , /0000-0003-1349-9608 FU Fonds quebecois de la recherche sur la nature et les technologies; National Institutes of Health [DP1-OD003646] FX Manuscript received October 18, 2010; revised December 28, 2010; accepted January 5, 2011. Date of publication February 10, 2011; date of current version May 18, 2011. This work was supported in part by the Fonds quebecois de la recherche sur la nature et les technologies, and in part by the National Institutes of Health under Grant DP1-OD003646. Asterisk indicates corresponding author. NR 12 TC 7 Z9 7 U1 0 U2 0 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 JUN PY 2011 VL 58 IS 6 BP 1507 EP 1510 DI 10.1109/TBME.2011.2113349 PG 4 WC Engineering, Biomedical SC Engineering GA 765UA UT WOS:000290732900001 PM 21317068 ER PT J AU Su, CW Cao, Y Kaplan, J Zhang, M Li, WL Conroy, M Walker, WA Shi, HN AF Su, Chien-Wen Cao, Yue Kaplan, Jess Zhang, Mei Li, Wanglin Conroy, Michelle Walker, W. Allan Shi, Hai Ning TI Duodenal Helminth Infection Alters Barrier Function of the Colonic Epithelium via Adaptive Immune Activation SO INFECTION AND IMMUNITY LA English DT Article ID HELIGMOSOMOIDES-POLYGYRUS; E-CADHERIN; RECIPROCAL REGULATION; NEMATODE INFECTION; ENTERIC NEMATODE; DENDRITIC CELLS; INDUCED COLITIS; TIGHT JUNCTION; MAST-CELLS; INTESTINE AB Chronic infection with intestinal helminth parasites is a major public health problem, particularly in the developing world, and can have significant effects on host physiology and the immune response to other enteric infections and antigens. The mechanisms underlying these effects are not well understood. In the current study, we investigated the impact of infection with the murine nematode parasite Heligmosomoides polygyrus, which resides in the duodenum, on epithelial barrier function in the colon. We found that H. polygyrus infection produced a significant increase in colonic epithelial permeability, as evidenced by detection of elevated serum levels of the tracer horseradish peroxidase following rectal administration. This loss of normal barrier function was associated with clear ultrastructural changes in the tight junctions of colonic epithelial cells and an alteration in the expression and distribution of the junctional protein E-cadherin. These parasite-induced abnormalities were not observed in SCID mice but did occur in SCID mice that were adoptively transferred with wild-type T cells, indicating a requirement for adaptive immunity. Furthermore, the helminth-induced increase in gut permeability was not seen in STAT6 knockout (KO) mice. Taken together, the results demonstrate that one of the mechanisms by which helminths exert their effects involves the lymphocyte-and STAT6-dependent breakdown of the intestinal epithelial barrier. This increase in epithelial permeability may facilitate the movement of lumenal contents across the mucosa, thus helping to explain how helminth infection can alter the immune response to enteric antigens. C1 [Shi, Hai Ning] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Shi, HN (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, Bldg 114,16th St,Room 3504, Charlestown, MA 02129 USA. EM shiha@helix.mgh.harvard.edu FU Clinical Nutrition Research Center at Harvard [P30 DK040561]; [R21DK074727]; [R01DK082427] FX This work was supported by R21DK074727 and R01DK082427 (to H.N.S.) and the Clinical Nutrition Research Center at Harvard (P30 DK040561). NR 40 TC 18 Z9 18 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2011 VL 79 IS 6 BP 2285 EP 2294 DI 10.1128/IAI.01123-10 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 765LJ UT WOS:000290707200016 PM 21444669 ER PT J AU Karlsson, P Cole, BF Colleoni, M Roncadin, M Chua, BH Murray, E Price, KN Castiglione-Gertsch, M Goldhirsch, A Gruber, G AF Karlsson, Per Cole, Bernard F. Colleoni, Marco Roncadin, Mario Chua, Boon H. Murray, Elizabeth Price, Karen N. Castiglione-Gertsch, Monica Goldhirsch, Aron Gruber, Guenther CA Int Breast Canc Study Grp TI TIMING OF RADIOTHERAPY AND OUTCOME IN PATIENTS RECEIVING ADJUVANT ENDOCRINE THERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Breast cancer; Radiotherapy; Radiotherapy timing; Breast-conserving surgery; Endocrine therapy ID BREAST-CONSERVING SURGERY; RADIATION-THERAPY; RANDOMIZED-TRIAL; CANCER PATIENTS; CHEMOTHERAPY; DELAY; RECURRENCE; EXPERIENCE; TIME AB Purpose: To evaluate the association between the interval from breast-conserving surgery (BCS) to radiotherapy (RT) and the clinical outcome among patients treated with adjuvant endocrine therapy. Patients and Methods: Patient information was obtained from three International Breast Cancer Study Group trials. The analysis was restricted to 964 patients treated with BCS and adjuvant endocrine therapy. The patients were divided into two groups according to the median number of days between BCS and RT and into four groups according to the quartile of time between BCS and RT. The endpoints were the interval to local recurrence, disease-free survival, and overall survival. Proportional hazards regression analysis was used to perform comparisons after adjustment for baseline factors. Results: The median interval between BCS and RT was 77 days. RT timing was significantly associated with age, menopausal status, and estrogen receptor status. After adjustment for these factors, no significant effect of a RT delay weeks was found. The adjusted hazard ratio for RT within 77 days vs. after 77 days was 0.94(95% confidence interval [CI], 0.47-1.87) for the interval to local recurrence, 1.05 (95% CI, 0.82-1.34) for disease-free survival, and 1.07 (95% CI, 0.77-1.49) for overall survival. For the interval to local recurrence the adjusted hazard ratio for <= 48, 49-77, and 78-112 days was 0.90(95% CI, 0.34-2.37), 0.86 (95% CI, 0.33-2.25), and 0.89 (95% CI, 0.33-2.41), respectively, relative to >= 113 days. Conclusion: A RT delay of <= 20 weeks was significantly associated with baseline factors such as age, menopausal status, and estrogen-receptor status. After adjustment for these factors, the timing of RT was not significantly associated with the interval to local recurrence, disease-free survival, or overall survival. (C) 2011 Elsevier Inc. C1 [Karlsson, Per] Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Oncol, S-41345 Gothenburg, Sweden. [Cole, Bernard F.] Univ Vermont, Dept Math & Stat, Coll Engn & Math Sci, Burlington, VT 05405 USA. [Cole, Bernard F.] Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Colleoni, Marco] European Inst Oncol, Res Unit Med Senol, Dept Med, Milan, Italy. [Roncadin, Mario] Ctr Riferimento Oncol, Dept Radiotherapy, I-33081 Aviano, Italy. [Chua, Boon H.] Peter MacCallum Canc Ctr, Dept Radiat Oncol, Melbourne, Vic, Australia. [Murray, Elizabeth] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Murray, Elizabeth] Groote Shuur Hosp, Dept Radiat Oncol, Cape Town, South Africa. [Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, Int Breast Canc Study Grp Stat Ctr, Boston, MA USA. [Castiglione-Gertsch, Monica] Int Breast Canc Study Grp Coordinating Ctr, Bern, Switzerland. [Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Goldhirsch, Aron] Oncol Inst So Switzerland, Bellinzona, Switzerland. [Gruber, Guenther] Klin Hirslanden, Inst Radiotherapie, Zurich, Switzerland. RP Karlsson, P (reprint author), Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Oncol, S-41345 Gothenburg, Sweden. EM per.karlsson@oncology.gu.se FU Swiss Group for Clinical Cancer Research; Frontier Science and Technology Research Foundation; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council); National Cancer Institute [CA-75362]; Swedish Cancer Society; Cancer Association of South Africa; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK) FX The International Breast Cancer Study Group was funded in part by the Swiss Group for Clinical Cancer Research, the Frontier Science and Technology Research Foundation, the Cancer Council Australia, the Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council), the National Cancer Institute (Grant CA-75362), the Swedish Cancer Society, the Cancer Association of South Africa, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). NR 16 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2011 VL 80 IS 2 BP 398 EP 402 DI 10.1016/j.ijrobp.2010.02.042 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 767EC UT WOS:000290837100012 PM 20729007 ER PT J AU Mori, S Kanematsu, N Asakura, H Sharp, GC Kumagai, M Dobashi, S Nakajima, M Yamamoto, N Kandatsu, S Baba, M AF Mori, Shinichiro Kanematsu, Nobuyuki Asakura, Hiroshi Sharp, Gregory C. Kumagai, Motoki Dobashi, Sugltru Nakajima, Mio Yamamoto, Naoyoshi Kandatsu, Susumu Baba, Masayuki TI FOUR-DIMENSIONAL LUNG TREATMENT PLANNING IN LAYER-STACKING CARBON ION BEAM TREATMENT: COMPARISON OF LAYER-STACKING AND CONVENTIONAL UNGATED/GATED IRRADIATION SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Carbon ion beam; CT; Four-dimensional; Layer-stacking; Lung; Treatment planning ID GATED RADIOTHERAPY; 3-DIMENSIONAL IRRADIATION; AUDIOVISUAL BIOFEEDBACK; PROTON RADIOTHERAPY; RADIATION-THERAPY; SCANNING SYSTEM; TUMOR MOTION; WAVE-FORM; CANCER; TRACKING AB Purpose: We compared four-dimensional (4D) layer-stacking and conventional carbon ion beam distribution in the treatment of lung cancer between ungated and gated respiratory strategies using 4DCT data sets. Methods and Materials: Twenty lung patients underwent 4DCT imaging under free-breathing conditions. Using planning target volumes (PTVs) at respective respiratory phases, two types of compensating bolus were designed, a full single respiratory cycle for the ungated strategy and an approximately 30% duty cycle for the exhalationgated strategy. Beams were delivered to the PTVs for the ungated and gated strategies, PTV(ungated) and PTV(gated), respectively, which were calculated by combining the respective PTV(Tn)s by layer-stacking and conventional irradiation. Carbon ion beam dose distribution was calculated as a function of respiratory phase by applying a compensating bolus to 4DCT. Accumulated dose distributions were calculated by applying deformable registration. Results: With the ungated strategy, accumulated dose distributions were satisfactorily provided to the PTV, with 1195 values for layer-stacking and conventional irradiation of 94.0% and 96.2%, respectively. V20 for the lung and Dmax for the spinal cord were lower with layer-stacking than with conventional irradiation, whereas Dmax for the skin (14.1 GyE) was significantly lower (21.9 GyE). In addition, dose conformation to the GTV/PTV with layer-stacking irradiation was better with the gated than with the ungated strategy. Conclusions: Gated layer-stacking irradiation allows the delivery of a carbon ion beam to a moving target without significant degradation of dose conformity or the development of hot spots. (C) 2011 Elsevier Inc. C1 [Mori, Shinichiro] Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Inage Ku, Chiba 2638555, Japan. [Sharp, Gregory C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Sharp, Gregory C.] Harvard Univ, Sch Med, Boston, MA USA. RP Mori, S (reprint author), Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Inage Ku, Chiba 2638555, Japan. EM shinshin@nirs.go.jp RI Kanematsu, Nobuyuki/B-9130-2008; OI Kanematsu, Nobuyuki/0000-0002-2534-9933; Mori, Shinichiro/0000-0002-0412-4399 NR 42 TC 8 Z9 8 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2011 VL 80 IS 2 BP 597 EP 607 DI 10.1016/j.ijrobp.2010.07.1982 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 767EC UT WOS:000290837100038 PM 20971576 ER PT J AU Zhao, H Goetz, MB AF Zhao, Hui Goetz, Matthew Bidwell TI Complications of HIV infection in an ageing population: challenges in managing older patients on long-term combination antiretroviral therapy SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Review DE immunocompromised host; epidemiology; age ID HUMAN-IMMUNODEFICIENCY-VIRUS; MYOCARDIAL-INFARCTION RATES; BONE-MINERAL DENSITY; HEALTH-CARE-SYSTEM; D-A-D; DIABETES-MELLITUS; NAIVE PATIENTS; RISK-FACTORS; CELL COUNT; RANDOMIZED-TRIAL AB With the use of combination antiretroviral therapy, the proportion of HIV-infected patients over age 50 has greatly increased. The rate of progression of untreated HIV disease, response to therapy and complicating effects of co-morbidities differ in older versus younger patients. Compared with younger individuals, older untreated HIV patients demonstrate faster rates of CD4+ cell loss and more rapid progression to AIDS and death. With treatment, older patients have a better virological response, but a less robust immunological response. The treatment of older HIV-infected patients is further complicated by pre-existing co-morbid conditions including cardiovascular, hepatic and metabolic complications that may be exacerbated by the effects of HIV infection per se, modest immunodeficiency (i.e. at CD4+ counts >350 cells/mm(3)), and the metabolic and other adverse effects of combination antiretroviral therapy. Based on these considerations guidelines for the treatment of HIV-infected patients state that increased age is a consideration in initiating antiretroviral therapy in persons with >350-500 CD4+ cells/mm(3). C1 [Zhao, Hui; Goetz, Matthew Bidwell] VA Greater Angeles Healthcare Syst, Infect Dis Sect, Dept Med, Los Angeles, CA 90073 USA. [Zhao, Hui] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Goetz, MB (reprint author), VA Greater Angeles Healthcare Syst, Infect Dis Sect 111F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM matthew.goetz@va.gov OI Goetz, Matthew/0000-0003-4542-992X NR 67 TC 8 Z9 8 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2011 VL 66 IS 6 BP 1210 EP 1214 DI 10.1093/jac/dkr058 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 763VM UT WOS:000290587800003 PM 21421583 ER PT J AU Harker, N Garefalaki, A Menzel, U Ktistaki, E Naito, T Georgopoulos, K Kioussis, D AF Harker, Nicola Garefalaki, Anna Menzel, Ursula Ktistaki, Eleni Naito, Taku Georgopoulos, Katia Kioussis, Dimitris TI Pre-TCR Signaling and CD8 Gene Bivalent Chromatin Resolution during Thymocyte Development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL DEVELOPMENT; HISTONE H3; REMODELING COMPLEXES; TRANSGENIC MICE; EXPRESSION; LINEAGE; LOCUS; IKAROS; DIFFERENTIATION; METHYLATION AB The CD8 gene is silent in CD4(-)CD8(-) double-negative thymocytes, expressed in CD4(+)CD8(+) double-positive cells, and silenced in cells committing to the CD4(+) single-positive (SP) lineage, remaining active in the CD8(+) SP lineage. In this study, we show that the chromatin of the CD8 locus is remodeled in C57BL/6 and B6/J Rag1(-/-) MOM double-negative thymocytes as indicated by DNaseI hypersensitivity and widespread bivalent chromatin marks. Pre-TCR signaling coincides with chromatin bivalency resolution into monovalent activating modifications in double-positive and CD8 SP cells. Shortly after commitment to CD4 SP cell lineage, monovalent repressive characteristics and chromatin inaccessibility are established. Differential binding of Ikaros, NuRD, and heterochromatin protein 1 alpha on the locus during these processes may participate in the complex regulation of CD8. The Journal of Immunology, 2011, 186: 6368-6377. C1 [Harker, Nicola; Garefalaki, Anna; Menzel, Ursula; Ktistaki, Eleni; Kioussis, Dimitris] Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England. [Naito, Taku] RIKEN, Res Ctr Allergy & Immunol, Transcript Regulat Lab, Yokohama, Kanagawa 2300045, Japan. [Georgopoulos, Katia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Harker, N (reprint author), Natl Inst Med Res, MRC, Div Mol Immunol, Ridgeway,Mill Hill, London NW7 1AA, England. EM nharker@nimr.mrc.ac.uk FU Medical Research Council UK [U117512796] FX This work was supported by the Medical Research Council UK (U117512796). NR 61 TC 12 Z9 12 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2011 VL 186 IS 11 BP 6368 EP 6377 DI 10.4049/jimmunol.1003567 PG 10 WC Immunology SC Immunology GA 766BX UT WOS:000290755700036 PM 21515796 ER PT J AU Rosenblatt, J Glotzbecker, B Mills, H Vasir, B Tzachanis, D Levine, JD Joyce, RM Wellenstein, K Keefe, W Schickler, M Rotem-Yehudar, R Kufe, D Avigan, D AF Rosenblatt, Jacalyn Glotzbecker, Brett Mills, Heidi Vasir, Baldev Tzachanis, Dimitrios Levine, James D. Joyce, Robin M. Wellenstein, Kerry Keefe, Whitney Schickler, Michael Rotem-Yehudar, Rinat Kufe, Donald Avigan, David TI PD-1 Blockade by CT-011, Anti-PD-1 Antibody, Enhances Ex Vivo T-cell Responses to Autologous Dendritic Cell/Myeloma Fusion Vaccine SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE PD-1 blockade; DC/tumor fusion cell; tumor vaccine; cancer vaccines; immunotherapy ID PROGRAMMED DEATH-1 LIGAND-1; MULTIPLE-MYELOMA; CLINICAL-SIGNIFICANCE; CARCINOMA-CELLS; DISEASE PROGRESSION; THERAPEUTIC TARGET; ANTITUMOR IMMUNITY; PROGNOSTIC-FACTORS; PANCREATIC-CANCER; PERIPHERAL-BLOOD AB We have developed a cancer vaccine in which autologous tumor is fused with dendritic cells (DCs) resulting in the presentation of tumor antigens in the context of DC-mediated costimulation. In clinical trials, immunologic responses have been observed, however responses may be muted by inhibitory pathways. The PD1/PDL1 pathway is an important element contributing to tumor-mediated immune suppression. In this study, we demonstrate that myeloma cells and DC/tumor fusions strongly express PD-L1. Compared with a control population of normal volunteers, increased PD-1 expression was observed on T cells isolated from patients with myeloma. It is interesting to note that after autologous transplantation, T-cell expression of PD-1 returned to levels seen in normal controls. We examined the effect of PD-1 blockade on T-cell response to DC/tumor fusions ex vivo. Presence of CT-011, an anti-PD1 antibody, promoted the vaccine-induced T-cell polarization towards an activated phenotype expressing Th1 compared with Th2 cytokines. A concomitant decrease in regulatory T cells and enhanced killing in a cytotoxicity assay was observed. In summary, we demonstrate that PD-1 expression is increased in T cells of patients with active myeloma, and that CT-011 enhances activated T-cell responses after DC/tumor fusion stimulation. C1 [Rosenblatt, Jacalyn; Glotzbecker, Brett; Mills, Heidi; Tzachanis, Dimitrios; Levine, James D.; Joyce, Robin M.; Wellenstein, Kerry; Keefe, Whitney; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Vasir, Baldev; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schickler, Michael; Rotem-Yehudar, Rinat] CureTech Ltd, Yavne, Israel. RP Rosenblatt, J (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,KS-121, Boston, MA 02215 USA. EM jrosenb1@bidmc.harvard.edu FU DOD [W81XWH-09-1-0296]; NIH [5 K12 CA087723]; CureTech, Ltd. FX Funding to conduct the study was obtained from the DOD (grant # W81XWH-09-1-0296 to David Avigan, MD), the NIH (K12 Clinical Research Career Development Program Award grant # 5 K12 CA087723 to Jacalyn Rosenblatt, MD), and by research funding obtained from CureTech, Ltd. to David Avigan, MD and Jacalyn Rosenblatt, MD. NR 51 TC 110 Z9 113 U1 2 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JUN PY 2011 VL 34 IS 5 BP 409 EP 418 DI 10.1097/CJI.0b013e31821ca6ce PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 766BD UT WOS:000290752500001 PM 21577144 ER PT J AU Brooks-Pollock, E Becerra, MC Goldstein, E Cohen, T Murray, MB AF Brooks-Pollock, Ellen Becerra, Mercedes C. Goldstein, Edward Cohen, Ted Murray, Megan B. TI Epidemiologic Inference From the Distribution of Tuberculosis Cases in Households in Lima, Peru SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MULTIDRUG-RESISTANT TUBERCULOSIS; COMMUNITY TRANSMISSION PARAMETERS; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; INFECTION; CONTACTS; DISEASE; RISK; REACTIVATION; METAANALYSIS AB Background. Tuberculosis (TB) often occurs among household contacts of people with active TB. It is unclear whether clustering of cases represents household transmission or shared household risk factors for TB. Methods. We used cross-sectional data from 764 households in Lima, Peru, to estimate the relative contributions of household and community transmission, the average time between cases, and the immunity afforded by a previous TB infection. Results. The distribution of cases per household suggests that almost 7 of 10 nonindex household cases were infected in the community rather than in the household. The average interval between household cases was 3.5 years. We observed a saturation effect in the number of cases per household and estimated that protective immunity conferred up to 35% reduction in the risk of disease. Conclusions. Cross-sectional household data can elucidate the natural history and transmission dynamics of TB. In this high-incidence setting, we found that the majority of cases were attributable to community transmission and that household contacts of case patients derive some immunity from household exposures. Screening of household contacts may be an effective method of detecting new TB cases if carried out over several years. C1 [Brooks-Pollock, Ellen; Goldstein, Edward; Cohen, Ted; Murray, Megan B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Becerra, Mercedes C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Becerra, Mercedes C.; Cohen, Ted; Murray, Megan B.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Murray, Megan B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Brooks-Pollock, E (reprint author), Univ Cambridge, Dept Vet Med, Madingley Rd, Cambridge CB3 0ES, England. EM ellen.brooks.pollock@gmail.com RI Cohen, Ted/G-8101-2011 FU National Institutes of Health [U19 AI0176217]; Charles H. Hood Foundation FX This work was supported by the National Institutes of Health (grant U19 AI0176217 [PI: MBM] to E. B. P., T. C. and M. B. M.) and the Charles H. Hood Foundation (M. B.). NR 40 TC 20 Z9 20 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2011 VL 203 IS 11 BP 1582 EP 1589 DI 10.1093/infdis/jir162 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 767LT UT WOS:000290858800012 PM 21592987 ER PT J AU Mamtani, M Mummidi, S Ramsuran, V Pham, MH Maldonado, R Begum, K Valera, MS Sanchez, R Castiblanco, J Kulkarni, H Ndung'u, T He, WJ Anaya, JM Ahuja, SK AF Mamtani, Manju Mummidi, Srinivas Ramsuran, Veron Pham, Minh-Hieu Maldonado, Robert Begum, Kazi Valera, Maria Soledad Sanchez, Racquel Castiblanco, John Kulkarni, Hemant Ndung'u, Thumbi He, Weijing Anaya, Juan Manuel Ahuja, Sunil K. TI Influence of Variations in CCL3L1 and CCR5 on Tuberculosis in a Northwestern Colombian Population SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RECEPTOR 5 GENE; HIV-1; EXPRESSION; SUSCEPTIBILITY; POLYMORPHISM; ASSOCIATION; HAPLOTYPES; CHEMOKINES; GENOTYPES AB We investigated the association of polymorphisms in CCR5, the major human immunodeficiency virus (HIV)-1 coreceptor, and copy number of its potent ligand CCL3L1 with tuberculosis in 298 individuals from Colombia. The CCR5-HHD haplotype, a known genetic determinant of increased susceptibility to HIV-AIDS, and a high copy number of CCL3L1, a known genetic determinant of enhanced CCL3/CCL3L1 chemokine expression, each associated with presence of tuberculosis. Furthermore, CCR5-HHD was associated with higher CCR5 gene and surface expression. These results substantiate the strong link between the pro-inflammatory effects of CCR5 and its ligands with active tuberculosis and suggest that chemokine-chemokine receptor genetic determinants may influence tuberculosis in addition to HIV/AIDS. C1 [Mamtani, Manju; Mummidi, Srinivas; Pham, Minh-Hieu; Maldonado, Robert; Begum, Kazi; Valera, Maria Soledad; Sanchez, Racquel; Castiblanco, John; Kulkarni, Hemant; He, Weijing; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Vet Adm Ctr AIDS & HIV Infect 1, San Antonio, TX USA. [Mamtani, Manju; Mummidi, Srinivas; Pham, Minh-Hieu; Maldonado, Robert; Begum, Kazi; Valera, Maria Soledad; Sanchez, Racquel; Castiblanco, John; Kulkarni, Hemant; He, Weijing; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX USA. [Mamtani, Manju; Mummidi, Srinivas; Pham, Minh-Hieu; Maldonado, Robert; Begum, Kazi; Valera, Maria Soledad; Sanchez, Racquel; Castiblanco, John; Kulkarni, Hemant; He, Weijing; Ahuja, Sunil K.] Univ Texas San Antonio, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Ramsuran, Veron; Ndung'u, Thumbi] Univ KwaZulu Natal, CAPRISA, Nelson R Mandela Sch Med, Durban, South Africa. [Ramsuran, Veron; Ndung'u, Thumbi] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, Durban, South Africa. [Anaya, Juan Manuel] Corp Invest Biol, Cellular Biol & Immunogenet Unit, Medellin, Colombia. [Anaya, Juan Manuel] Univ Rosario, Sch Med, Bogota, Colombia. RP Ahuja, SK (reprint author), VA Ctr Personalized Med, San Antonio, TX 78229 USA. EM ahujas@uthscsa.edu RI CASTIBLANCO, JOHN/B-6599-2009; Mummidi, Srinivas/C-1004-2008; Anaya, Juan-Manuel/J-1960-2016; OI CASTIBLANCO, JOHN/0000-0002-7965-9822; Ndung'u, Thumbi/0000-0003-2962-3992; Mummidi, Srinivas/0000-0002-4068-6380; Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario, Biblioteca/0000-0003-3491-9392; CASTIBLANCO, JOHN/0000-0003-2556-3697 FU Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System; NIH [R37046326]; VA MERIT award; Elizabeth Glaser Scientist Award; Burroughs Wellcome Clinical Scientist Award in Translational Research; Doris Duke Distinguished Clinical Scientist Award FX This work was supported by the Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System, and the NIH (R37046326), a VA MERIT award, the Elizabeth Glaser Scientist Award, the Burroughs Wellcome Clinical Scientist Award in Translational Research, and the Doris Duke Distinguished Clinical Scientist Award to S. K. A. The work was also supported by a VA MERIT award to S. M. NR 16 TC 13 Z9 15 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2011 VL 203 IS 11 BP 1590 EP 1594 DI 10.1093/infdis/jir145 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 767LT UT WOS:000290858800013 PM 21592988 ER PT J AU Gerstner, ER Eichler, AF Plotkin, SR Drappatz, J Doyle, CL Xu, L Duda, DG Wen, PY Jain, RK Batchelor, TT AF Gerstner, Elizabeth R. Eichler, April F. Plotkin, Scott R. Drappatz, Jan Doyle, Colin L. Xu, Lei Duda, Dan G. Wen, Patrick Y. Jain, Rakesh K. Batchelor, Tracy T. TI Phase I trial with biomarker studies of vatalanib (PTK787) in patients with newly diagnosed glioblastoma treated with enzyme inducing anti-epileptic drugs and standard radiation and temozolomide SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Angiogenesis; Biomarkers; Clinical trial; Glioblastoma; Treatment ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; VASCULAR NORMALIZATION; MALIGNANT GLIOMA; TUMOR; CANCER; IMATINIB; SU11248; BLOOD AB Targeting angiogenesis in glioblastoma (GBM) may improve patient outcome by normalizing tumor vasculature and improving delivery of chemotherapeutics and oxygen. Consequently, concomitant administration of small molecule inhibitors of the VEGF pathway will likely have a positive impact on chemoradiation treatment outcome. We conducted a Phase I study of vatalanib, a small molecule inhibitor of VEGFR, PDGFR, and c-kit in patients with newly diagnosed GBM receiving radiation, temozolomide, and an enzyme-inducing anti-epileptic drug in order to determine the MTD of vatalanib in this patient population. We incorporated circulating biomarker and SNP analyses and pharmacokinetic studies. Nineteen patients were enrolled and the MTD was not reached at the time of study termination. Vatalanib was well tolerated with only 2 DLTs (thrombocytopenia and elevated transaminases). Other grade 3/4 toxicities included leukopenia, lymphopenia, neutropenia, and hand-foot syndrome. There were no wound-healing complications. Of the 13 patients evaluable for a radiographic response, 2 had a partial response and 9 had stable disease. Vatalanib significantly increased PlGF and sVEGFR1 in plasma circulation and decreased sVEGFR2 and sTie2. Plasma collagen IV increased significantly by day 50 of treatment. Vatalanib was well tolerated and this study demonstrates the safety of oral small molecule inhibitors in newly diagnosed GBM patients. Blood biomarkers may be useful as pharmacodynamic markers of response to anti-angiogenic therapies. C1 [Gerstner, Elizabeth R.; Eichler, April F.; Plotkin, Scott R.; Doyle, Colin L.; Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Drappatz, Jan; Wen, Patrick Y.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Xu, Lei; Duda, Dan G.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA. RP Gerstner, ER (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stephen E & Catherine Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM egerstner@partners.org FU NCI NIH HHS [K24 CA125440] NR 19 TC 36 Z9 36 U1 1 U2 6 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 JUN PY 2011 VL 103 IS 2 BP 325 EP 332 DI 10.1007/s11060-010-0390-7 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 766IB UT WOS:000290773100016 PM 20821342 ER PT J AU Thompson, EM Dosa, E Kraemer, DF Neuwelt, EA AF Thompson, Eric M. Dosa, Edit Kraemer, Dale F. Neuwelt, Edward A. TI Correlation of MRI sequences to assess progressive glioblastoma multiforme treated with bevacizumab SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Bevacizumab; Macdonald criteria; FLAIR; Progressive malignant glioma ID RECURRENT MALIGNANT GLIOMA; GRADE GLIAL TUMORS; PHASE-II; IRINOTECAN; EFFICACY; MODEL; CARBOPLATIN; SURVIVAL; CRITERIA; VOLUME AB In the context of bevacizumab therapy for the treatment of progressive malignant gliomas, it is currently unclear how different magnetic resonance imaging (MRI) sequences correlate with each other over time. The objective of this study was to determine if a reliable and predictable relationship over time exists between post-gadolinium based contrast agent T1-weighted (T1 + GBCA), T2-weighted, and FLAIR MRI in patients with progressive glioblastoma multiforme (GBM) receiving bevacizumab and chemotherapy. The MRI lesion volumes of 10 patients with progressive GBM that received bevacizumab plus chemotherapy were manually calculated by two independent reviewers. T2 and FLAIR volumes were analyzed by analysis of covariance (ANCOVA) as a function of T1 + GBCA lesion enhancement volume, reviewer, and time interval between MRI acquisitions. Pearson product moment correlation (r) was used to compare pre and post treatment volumes for the group of 10 patients and for each individual patient over their treatment course. ANCOVA demonstrated a significant association between T1 + GBCA and T2-weighted volumes (P = 0.0006) and between T1 + GBCA and FLAIR volumes (P < 0.0001). These associations remained constant over time. The correlation between T1 + GBCA and both T2-weighted and FLAIR volumes improved after bevacizumab treatment. Individual correlations between T1 + GBCA and FLAIR were strong (r a parts per thousand yen 0.63) with one exception, while correlations between T1 + GBCA and T2 were more variable (r = 0.18-0.99). These findings suggest that FLAIR MRI should be evaluated in addition to T1 + GBCA MRI when evaluating GBM responses. C1 [Thompson, Eric M.; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA. [Dosa, Edit; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Kraemer, Dale F.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Kraemer, Dale F.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Kraemer, Dale F.] Oregon Hlth & Sci Univ, Dept Pharm Practice, Oregon State Univ, Coll Pharm, Portland, OR 97239 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA. EM neuwelte@ohsu.edu NR 22 TC 6 Z9 6 U1 0 U2 3 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 JUN PY 2011 VL 103 IS 2 BP 353 EP 360 DI 10.1007/s11060-010-0397-0 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 766IB UT WOS:000290773100019 PM 20848300 ER PT J AU Lessell, S AF Lessell, Simmons TI Pitfalls in Imaging SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Editorial Material ID INTRACRANIAL ANEURYSMS C1 [Lessell, Simmons] Massachusetts Eye & Ear Infirm, Neuroophthalmol Unit, Boston, MA 02114 USA. [Lessell, Simmons] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lessell, S (reprint author), Massachusetts Eye & Ear Infirm, Neuroophthalmol Unit, 243 Charles St, Boston, MA 02114 USA. EM simmons_lessell@meei.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD JUN PY 2011 VL 31 IS 2 BP 101 EP 102 DI 10.1097/WNO.0b013e318219c906 PG 2 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 766LO UT WOS:000290784000002 PM 21593626 ER PT J AU Rizzo, JF AF Rizzo, Joseph F., III TI Update on Retinal Prosthetic Research: The Boston Retinal Implant Project SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Review ID GANGLION-CELLS; ELECTRICAL-STIMULATION; ARTIFICIAL VISION; SUBRETINAL IMPLANTATION; PERCEPTUAL THRESHOLDS; RETINITIS-PIGMENTOSA; DEGENERATION; ACTIVATION; RESPONSES; PERFORMANCE AB The field of retinal prosthetic research, now more than 20 years old, has producedmany high-quality technical options that have the potential to restore vision to patients with acquired disease of the outer retina. Five companies have performed Phase I clinical trials demonstrating that blind patients can reliably report basic elements of visual percepts induced by electrical stimulation. However, at present patients and observers generally do not consider the results to be useful enough in the performance of tasks of daily living to justify the risks of surgery and chronic implantation or the costs. Having developed a wireless device implanted in the subretinal space, the Boston Retinal Implant Project has focused its efforts on developing scalable technologies to create a hermetic device that can deliver individually controlled pulses of electrical stimulation to each of hundreds of electrodes. An advanced device with such attributes will be needed to justify the risks of implantation. An assessment of long-term biocompatibility for all devices remains to be done. C1 [Rizzo, Joseph F., III] Harvard Univ, Sch Med, Dept Vet Adm, Boston, MA USA. [Rizzo, Joseph F., III] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02458 USA. RP Rizzo, JF (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02458 USA. EM joseph_rizzo@meei.harvard.edu NR 64 TC 42 Z9 42 U1 0 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD JUN PY 2011 VL 31 IS 2 BP 160 EP 168 DI 10.1097/WNO.0b013e31821eb79e PG 9 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 766LO UT WOS:000290784000015 PM 21593628 ER PT J AU Ruchelsman, DE Ramos, LE Price, AE Grossman, LA Valencia, H Grossman, JAI AF Ruchelsman, David E. Ramos, Lorna E. Price, Andrew E. Grossman, Leslie Agatha Valencia, Herbert Grossman, John A. I. TI Outcome After Tendon Transfers to Restore Wrist Extension in Children With Brachial Plexus Birth Injuries SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE tendon transfer; brachial plexus; extensor paralysis ID HAND AB Children with brachial plexus birth injuries often require tendon transfer to restore active wrist extension and maximize hand function. The purpose of this study is to assess the clinical results in children with brachial plexus birth injuries after tendon transfer to reconstruct active wrist extension. Over a 10-year period, 21 children (11 male, 10 female) underwent tendon transfer to reconstruct active wrist extension by a single surgeon. Eight patients had C5/C6/C7 injury and 13 patients had global palsy (C5-T1). The average age at surgery was 5.5 years (range, 3 to 8 y). Restoration of wrist extension was measured according to the functional scale of Duclos and Gilbert. The mean duration of follow-up was 36 months (minimum follow-up of 1 y). At latest follow-up, 14 (66%) children (C5/C6/C7, n = 8; global, n = 6) demonstrated active wrist extension >= 30 degrees. Within the global injury subcohort, 3 patients demonstrated static extension of the wrist. Four failures occurred in the global palsy group. Children with absent active wrist extension after a brachial plexus birth injury can benefit from a tendon transfer. The more severe global palsy cases have a worse outcome. C1 [Ramos, Lorna E.; Price, Andrew E.; Grossman, Leslie Agatha; Valencia, Herbert; Grossman, John A. I.] Miami Childrens Hosp, Brachial Plexus Program, Miami, FL 33243 USA. [Ruchelsman, David E.; Grossman, Leslie Agatha] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. [Ruchelsman, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA USA. [Ramos, Lorna E.; Price, Andrew E.; Grossman, Leslie Agatha; Valencia, Herbert; Grossman, John A. I.] NYU Hosp Joint Dis, Dept Orthoped Surg, New York, NY USA. RP Grossman, JAI (reprint author), Miami Childrens Hosp, Brachial Plexus Program, POB 430942, Miami, FL 33243 USA. EM drg@handandnervespecialist.com NR 6 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD JUN PY 2011 VL 31 IS 4 BP 455 EP 457 DI 10.1097/BPO.0b013e31821adcc0 PG 3 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 763MN UT WOS:000290562300019 PM 21572285 ER PT J AU Nadazdin, O Abrahamian, G Boskovic, S Smith, RN Schoenfeld, DA Madsen, JC Colvin, RB Sachs, DH Cosimi, AB Kawai, T AF Nadazdin, Ognjenka Abrahamian, Gregory Boskovic, Svjetlan Smith, Rex-Neal Schoenfeld, David A. Madsen, Joren C. Colvin, Robert B. Sachs, David H. Cosimi, A. Benedict Kawai, Tatsuo TI Stem Cell Mobilization and Collection for Induction of Mixed Chimerism and Renal Allograft Tolerance in Cynomolgus Monkeys SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE kidney transplantation; nonhuman primates; tolerance; mixed chimerism; peripheral blood stem cell transplantation; leukapheresis ID BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; NONHUMAN-PRIMATES; PROGENITOR CELLS; IMMUNOSUPPRESSION; IRRADIATION; BLOCKADE; SURVIVAL; REGIMEN; TRIAL AB Background. We have previously observed that donor bone marrow hematopoietic stem cells successfully induce transient mixed chimerism and renal allograft tolerance following non-myeloablative conditioning of the recipient. Stem cells isolated from the peripheral blood (PBSC) may provide similar benefits. We sought to determine the most effective method of mobilizing PBSC for this approach and the effects of differing conditioning regimens on their engraftment. Methods. A standard dose (10 mu g/kg) or high dose (100 mu g/kg) of granulocyte colony-stimulating factor (GCSF) with or without stem cell factor (SCF) was administered to the donor, and PBSC were collected by leukapheresis. Cynomolgus monkey recipients underwent a nonmyeloablative conditioning regimen (total body irradiation, thymic irradiation, and ATG) with splenectomy (splenectomy group) or a short course of anti-CD154 antibody (aCD154) (aCD154 group). Recipients then received combined kidney and PBSC transplantation and a 1-mo post-transplant course of cyclosporine. Results. Treatments with either two cytokines (GCSF + SCF) or high dose GCSF provided significantly more hematopoietic progenitor cells than standard dose GCSF alone. Recipients in the aCD154 group developed significantly higher myeloid and lymphoid chimerism (P < 0.0001 and P = 0.0002, respectively) than those in the splenectomy group. Longer term renal allograft survival without immunosuppression was also observed in the aCD154 group, while two of three recipients in the splenectomy group rejected their allografts soon after discontinuation of immunosuppression. Conclusions. Protocols including administration of two cytokines (GCSF + SCF) or high dose GCSF alone significantly mobilized more PBSC than standard dose GCSF alone. The recipients of PBSC consistently developed excellent chimerism and survived long-term without immunosuppression, when treated with CD154 blockade. (C) 2011 Elsevier Inc. All rights reserved. C1 [Nadazdin, Ognjenka; Abrahamian, Gregory; Boskovic, Svjetlan; Schoenfeld, David A.; Madsen, Joren C.; Cosimi, A. Benedict; Kawai, Tatsuo] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Smith, Rex-Neal; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Schoenfeld, David A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Sachs, David H.] Massachusetts Gen Hosp E, Transplantat Biol Res Ctr, Charlestown, MA USA. RP Kawai, T (reprint author), Massachusetts Gen Hosp, Transplant Ctr, White 521,55 Fruit St, Boston, MA 02114 USA. EM tkawai@partners.org FU NHL-BI [5U19DK080652-02]; NIH-NIAID; NIH/NIAID [5R01 AI50987-03]; [POI-HL18646]; [ROIA137692] FX The authors acknowledge support in part for this study by 5U19DK080652-02 NHL-BI, POI-HL18646, NIH-NIAID, ROIA137692, and NIH/NIAID 5R01 AI50987-03. The authors thank Dr. Elizabeth Smoot for statistical analysis, Patricia Della Pelle for pathologic analysis, and Drs. Michael Duggan and Elisabeth Moeller for anesthesia and postoperative care. NR 19 TC 4 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN PY 2011 VL 168 IS 2 BP 294 EP 300 DI 10.1016/j.jss.2010.02.027 PG 7 WC Surgery SC Surgery GA 768BZ UT WOS:000290907800021 PM 20605588 ER PT J AU de Prost, N El-Karak, C Avila, M Ichinose, F Melo, MFV AF de Prost, Nicolas El-Karak, Claudine Avila, Maria Ichinose, Fumito Melo, Marcos F. Vidal TI Changes in cysteinyl leukotrienes during and after cardiac surgery with cardiopulmonary bypass in patients with and without chronic obstructive pulmonary disease SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; EXHALED BREATH CONDENSATE; HEALTHY-SUBJECTS; LUNG INJURY; METABOLISM; COPD; MONTELUKAST; MEDIATORS; OUTCOMES; ASPIRIN AB Objective: Pulmonary function frequently deteriorates after cardiopulmonary bypass (CPB). Chronic obstructive pulmonary disease (COPD) increases risk of respiratory complications after CPB. Cysteinyl leukotrienes are important mediators of respiratory dysfunction. Their role during cardiac surgery and its lung complications is incompletely understood. We studied whether production of cysteinyl leukotrienes changes during and after cardiac surgery with CPB and differs between patients with and without COPD. Methods: Patients with (n = 9) and without (n = 10) moderate-to-severe COPD undergoing cardiac surgery with CPB were prospectively included. Plasma and urinary cysteinyl leukotriene and leukotriene B(4) concentrations were measured by enzyme-linked immunosorbent assay after anesthesia induction, at end of CPB, after CPB, and 2 hours after intensive care unit admission. Gas exchange and respiratory mechanics were also assessed. Results: Patients with COPD had larger airway resistances after CPB and chest closure (P <. 001), lower ratio of arterial Po(2) to inspired oxygen fraction at intensive care unit admission (215 +/- 37 vs 328 +/- 30 mm Hg, P <. 05), and longer postoperative mechanical ventilation (13.7 +/- 5.8 vs 6.8 +/- 3.4 hours, P <. 01). Urinary cysteinyl leukotriene concentrations increased with time in both groups (P <. 01), but more in patients with than without COPD (P <. 05). Plasma cysteinyl leukotriene concentrations increased significantly between baseline and intensive care unit admission in patients with but not without COPD (P <. 01). Concentrations of leukotriene B(4) in plasma and urine did not increase significantly with time and were not different between groups. Conclusions: Release of cysteinyl leukotrienes increases during cardiac surgery with CPB and is larger in patients with than without COPD. This may be related to higher lung and airway production of cysteinyl leukotrienes and neutrophil activation in patients with COPD. (J Thorac Cardiovasc Surg 2011;141:1496-502) C1 [Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mvidalmelo@partners.org OI de Prost, Nicolas/0000-0002-4833-4320 FU La Societe de Pneumologie de Langue Francaise; National Institutes of Health [R01HL101930]; Merck Co. FX Supported by an investigator-initiated grant from Merck & Co. Nicolas de Prost was supported by a scholarship from La Societe de Pneumologie de Langue Francaise, and Fumito Ichinose was supported by the National Institutes of Health R01HL101930. NR 34 TC 3 Z9 3 U1 0 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 JUN PY 2011 VL 141 IS 6 BP 1496 EP U208 DI 10.1016/j.jtcvs.2011.01.035 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 765MJ UT WOS:000290710900029 PM 21377695 ER PT J AU Park, ER Japuntich, S Temel, J Lanuti, M Pandiscio, J Hilgenberg, J Davies, D Dresler, C Rigotti, NA AF Park, Elyse R. Japuntich, Sandra Temel, Jennifer Lanuti, Michael Pandiscio, Jennifer Hilgenberg, Joanna Davies, Diane Dresler, Carolyn Rigotti, Nancy A. TI A Smoking Cessation Intervention for Thoracic Surgery and Oncology Clinics A Pilot Trial SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; Smoking; Cessation; Pharmacotherapy; Counseling ID CELL LUNG-CANCER; QUALITY-OF-LIFE; TOBACCO USE OUTCOMES; 2ND PRIMARY CANCERS; NECK-CANCER; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; CHILDHOOD-CANCER; DEPRESSION SCALE; HOSPITAL ANXIETY AB Introduction: Although most smokers diagnosed with lung cancer report that they want to quit smoking, many do not succeed. Smokers who quit when lung cancer is diagnosed have improved treatment efficacy, quality of life, and survival. Effective smoking cessation interventions targeted to thoracic oncology patients are needed. Methods: This pilot study examined the feasibility and potential efficacy of a 12-week program that combined smoking cessation counseling with varenicline. Seven-day point prevalence tobacco abstinence rates at the end of treatment were compared with a usual care control group. From January 2008 to August 2009, patients with a diagnosed or suspected thoracic malignancy were recruited at their initial visit to a thoracic surgeon or thoracic oncologist at Massachusetts General Hospital. Results: Of 1130 patients screened, 187 (17%) were current smokers, and an additional 66 (6%) reported quitting within the past 6 months. One hundred sixteen (67%) of smokers were eligible, and 49 (42%) of eligible smokers enrolled (control group n = 17, intervention group n = 32). Intervention participants completed a median of nine counseling sessions; 50% of intervention participants completed the full varenicline course. At 12-week follow-up, biochemically validated 7-day point prevalence tobacco abstinence rates were 34.4% in the intervention group versus 14.3% in the control group (odds ratio = 3.14, 95% confidence interval = 0.59-16.62, p = 0.18). Conclusion: Our findings support the feasibility and acceptability of this program. At the end of treatment, quit rates were higher in the control group. Further testing is indicated to establish the efficacy of this treatment package in a randomized clinical trial. C1 [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Park, Elyse R.; Japuntich, Sandra; Pandiscio, Jennifer; Hilgenberg, Joanna; Rigotti, Nancy A.] Harvard Univ, Sch Med, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Park, Elyse R.; Japuntich, Sandra; Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Lanuti, Michael; Davies, Diane] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Dresler, Carolyn] Arkansas Dept Hlth, Tobacco Prevent & Cessat Program, Little Rock, AR 72205 USA. RP Park, ER (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM epark@partners.org FU Nabi Biopharmaceuticals FX Nancy A. Regotti, MD, is an unpaid consultant to Pfizer and Free & Clear, Inc. Her institution also received a research grant from Nabi Biopharmaceuticals. Elyse R. Park, PhD, MPH, received a grant for research. Pfizer provided the medication for this pilot trial. NR 49 TC 26 Z9 26 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 BP 1059 EP 1065 DI 10.1097/JTO.0b013e318215a4dc PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 766FM UT WOS:000290766400012 PM 21512406 ER PT J AU Fadda, L O'Connor, GM Kumar, S Piechocka-Trocha, A Gardiner, CM Carrington, M McVicar, DW Altfeld, M AF Fadda, Lena O'Connor, Geraldine M. Kumar, Swati Piechocka-Trocha, Alicja Gardiner, Clair M. Carrington, Mary McVicar, Daniel W. Altfeld, Marcus TI Common HIV-1 Peptide Variants Mediate Differential Binding of KIR3DL1 to HLA-Bw4 Molecules SO JOURNAL OF VIROLOGY LA English DT Article ID HLA-B; NK CELLS; INFECTION; MUTATION; RECEPTOR; AIDS; SUBTYPES; ESCAPE; GAG AB Epidemiological studies have shown the protective effect of KIR3DL1/HLA-Bw4 genotypes in human immunodeficiency virus type 1 (HIV-1) infection; however, the functional correlates for the protective effect remain unknown. We investigated whether human leukocyte antigen (HLA)-Bw4-presented HIV-1 peptides could affect the interaction between the inhibitory natural killer (NK) cell receptor KIR3DL1 and its ligand HLA-Bw4. Distinct HIV-1 epitopes differentially modulated the binding of KIR3DL1 to HLA-Bw4. Furthermore, cytotoxic T lymphocyte (CTL) escape mutations within the immunodominant HLA-B57 (Bw4)-restricted Gag epitope TSTLQEQIGW abrogated KIR3DL1 binding to HLA-B57, suggesting that sensing of CTL escape variants by NK cells can contribute to the protective effect of the KIR3DL1/HLA-Bw4 compound genotype. C1 [Fadda, Lena; Kumar, Swati; Piechocka-Trocha, Alicja; Carrington, Mary; Altfeld, Marcus] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Charlestown, MA 02129 USA. [O'Connor, Geraldine M.; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Gardiner, Clair M.] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin, Ireland. [Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Bldg 149,13th St, Charlestown, MA 02129 USA. EM maltfeld@partners.org RI McVicar, Daniel/G-1970-2015 FU NIH [RO1AI067031]; Doris Duke Charitable Foundation; Bill and Melinda Gates Foundation; Susan and Philip T. Ragon Foundation; Ragon Institute of MGH, MIT, and Harvard; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX These studies were supported by the NIH (RO1AI067031), the Doris Duke Charitable Foundation, the Bill and Melinda Gates Foundation, and the Susan and Philip T. Ragon Foundation. L. F. is supported by a Ragon Fellowship of the Ragon Institute of MGH, MIT, and Harvard. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 17 TC 37 Z9 40 U1 0 U2 7 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 JUN PY 2011 VL 85 IS 12 BP 5970 EP 5974 DI 10.1128/JVI.00412-11 PG 5 WC Virology SC Virology GA 766CD UT WOS:000290756600025 PM 21471246 ER PT J AU Woodard, LD Urech, T Landrum, CR Wang, D Petersen, LA AF Woodard, LeChauncy D. Urech, Tracy Landrum, Cassie R. Wang, Degang Petersen, Laura A. TI Impact of Comorbidity Type on Measures of Quality for Diabetes Care SO MEDICAL CARE LA English DT Article DE diabetes mellitus; quality of health care; comorbidity ID UNITED-STATES; PERFORMANCE-MEASURES; HYPERTENSION; MEDICATION; IMPROVEMENT; DEPRESSION; PREVALENCE; ADHERENCE; OUTCOMES; DISEASE AB Objective: Studies provide conflicting results about the impact of comorbid conditions on the quality of chronic illness care. We assessed the effect of comorbidity type (concordant, discordant, or both) on the receipt of guideline-recommended care among patients with diabetes. Research Design: Patients were assigned to 1 of 4 condition groups: diabetes-concordant (hypertension, ischemic heart disease, hyperlipidemia), and/or diabetes-discordant (arthritis, depression, chronic obstructive pulmonary disease) conditions, or neither. We evaluated hemoglobin A1c, blood pressure, and low-density lipoprotein cholesterol readings at index and measured overall good quality of diabetes care, including a 6-month follow-up interval. We assessed the effect of condition group on overall good quality of care with logistic regression and generalized ordered logistic regression. Results: We assigned 35,872 patients to the diabetes comorbid condition groups, ranging from 2.0% in the discordant-only group to 58.0% in the concordant-only group. Patients with both types of conditions were more likely than those with no comorbidities to receive overall good quality for glycemic [odds ratio (OR), 2.13; 95% confidence interval (CI), 1.86-2.41], blood pressure (OR, 1.62; 95% CI, 1.40-1.84), and low-density lipoprotein cholesterol (OR, 3.57; 95% CI, 3.08-4.05) control within 6 months of an index visit. They were also more likely to receive overall good quality for all 3 quality measures combined (OR, 2.17; 95% CI, 1.96-2.39). Conclusions: Patients with the greatest clinical complexity were more likely than less complex patients to receive high quality diabetes care, suggesting that increased complexity does not necessarily predispose chronically ill patients to receiving poorer care. However, caution should be used in treating certain patient groups, such as the elderly, for whom adherence to multiple condition-specific guidelines may lack benefit or cause harm. C1 [Woodard, LeChauncy D.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Hlth Policy & Qual Program, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Woodard, LD (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Hlth Policy & Qual Program, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM woodard.lechauncy@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [PPO 09-316, IIR 04-349]; National Institutes of Health [R01 HL079173-01]; Houston VA HSR&D Center of Excellence [HFP90-020]; Dr Petersen was a Robert Wood Johnson Foundation [045444]; American Heart Association [0540043N] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, (PPO 09-316, PI LeChauncy D. Woodard, MD, MPH), (IIR 04-349, PI Laura A. Petersen, MD, MPH), National Institutes of Health (R01 HL079173-01, PI Laura A. Petersen, MD, MPH), and Houston VA HSR&D Center of Excellence HFP90-020 (PI Laura A. Petersen, MD, MPH). Dr Petersen was a Robert Wood Johnson Foundation Generalist Physician Faculty Scholar (grant number 045444) and an American Heart Association Established Investigator Awardee (grant number 0540043N) at the time this work was conducted. Dr Woodard is an assistant professor at the Michael E. DeBakey VA Medical Center Health Services Research and Development Center of Excellence, Houston, Texas. The funding sources played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 25 TC 30 Z9 30 U1 1 U2 16 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 JUN PY 2011 VL 49 IS 6 BP 605 EP 610 DI 10.1097/MLR.0b013e31820f0ed0 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 763MS UT WOS:000290563600013 PM 21422952 ER PT J AU Shwartz, M Cohen, AB Restuccia, JD Ren, ZJ Labonte, A Theokary, C Kang, R Horwitt, J AF Shwartz, Michael Cohen, Alan B. Restuccia, Joseph D. Ren, Z. Justin Labonte, Alan Theokary, Carol Kang, Raymond Horwitt, Jedediah TI How Well Can We Identify the High-Performing Hospital? SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE high-performing hospital; performance measures; quality; composite measures ID ACUTE MYOCARDIAL-INFARCTION; REGIONAL-VARIATIONS; MORTALITY-RATES; QUALITY; CARE; ASSOCIATION; OUTCOMES; COSTS; SATISFACTION; ADJUSTMENT AB Sharing lessons from high-performing hospitals facilitates quality improvement. High-performing hospitals have usually been identified using a small number of performance measures. The objective was to analyze how well 1,006 hospitals performed across a broader range of measures. Five measures were developed from publicly available data: adherence to processes of care, 30-day readmission rates, in-hospital mortality, efficiency, and patient satisfaction. For a subset of hospitals, the authors included two survey-based assessments of patient care quality, one by chief quality officers and one by frontline clinicians. In general, there was little correlation among the publicly available measures (r <= .10), though there was notable correlation between objective measures and survey-based measures (r = .23). Hospitals that performed well on a composite measure calculated from the publicly available measures were often not in the top quintile on most individual measures. This highlights the challenge in identifying high-performing hospitals to learn organizational-level best practices. C1 [Shwartz, Michael] Boston Univ, Sch Management, Boston, MA 02215 USA. [Shwartz, Michael; Cohen, Alan B.; Restuccia, Joseph D.; Labonte, Alan] VA Boston Healthcare Syst, Boston, MA USA. [Kang, Raymond] Northwestern Univ, Chicago, IL 60611 USA. RP Shwartz, M (reprint author), Boston Univ, Sch Management, 595 Commonwealth Ave, Boston, MA 02215 USA. EM mshwartz@bu.edu FU Commonwealth Fund FX This study was supported by a grant from the Commonwealth Fund. NR 38 TC 11 Z9 11 U1 3 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD JUN PY 2011 VL 68 IS 3 BP 290 EP 310 DI 10.1177/1077558710386115 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 758ZX UT WOS:000290209600002 PM 21156708 ER PT J AU Newcomb, LW Koltyn, KF Morgan, WP Cook, DB AF Newcomb, Lauren W. Koltyn, Kelli F. Morgan, William P. Cook, Dane B. TI Influence of Preferred versus Prescribed Exercise on Pain in Fibromyalgia SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE PHYSICAL ACTIVITY; CHRONIC PAIN; RPE; EXERCISE PRESCRIPTION ID STRESS-INDUCED ANALGESIA; CHRONIC-FATIGUE-SYNDROME; PHYSICAL-ACTIVITY; AEROBIC EXERCISE; IMPACT QUESTIONNAIRE; MECHANISMS; CONTRACTION; THRESHOLDS; PERCEPTION; RESPONSES AB NEWCOMB, L. W., K. F. KOLTYN, W. P. MORGAN, and D. B. COOK. Influence of Preferred versus Prescribed Exercise on Pain in Fibromyalgia. Med. Sci. Sports Exerc., Vol. 43, No. 6, pp. 1106-1113, 2011. Purpose: The purpose of this study was to examine the influence of a preferred-versus a prescribed-intensity exercise session on pain in women with fibromyalgia (FM). Methods: Twenty-one women with FM (mean age = 44 yr) completed two randomly assigned exercise sessions consisting of 20 min of cycle ergometry at a self-selected intensity and a prescribed intensity. Experimental pain perception was assessed before and after aerobic exercise. During exercise, HR, watts, RPE, and muscle pain were assessed every 5 min. Clinical pain was assessed with the Short-Form McGill Pain Questionnaire (SF-MPQ) immediately and 24, 48, 72, and 96 h after exercise. Data were analyzed with repeated-measures ANOVA. Results: Women with FM preferred a lower intensity of exercise than what was prescribed as indicated by significantly lower HR, watts, and RPE responses (P < 0.05). Muscle pain in the legs, however, was similar in the two conditions and significantly increased during exercise (P < 0.05). Pain thresholds and pain tolerances increased significantly after exercise, whereas peak pain ratings decreased after exercise (P < 0.05). Furthermore, pain (SF-MPQ) in the follow-up period was found to be lower than baseline (P < 0.05). Conclusions: It is concluded that the women with FM who participated in this study experienced significant improvements in pain after exercise. The results from this study are novel and indicate that recommendations for exercise prescription for individuals with FM should consider the preferred-intensity exercise model as a strategy to reduce pain. C1 [Newcomb, Lauren W.; Koltyn, Kelli F.; Morgan, William P.; Cook, Dane B.] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. [Cook, Dane B.] William S Middleton Mem Vet Adm Med Ctr, Res Serv, Madison, WI USA. RP Cook, DB (reprint author), Univ Wisconsin, Dept Kinesiol, 2000 Observ Dr, Madison, WI 53706 USA. EM dcook@education.wisc.edu FU Diane and Donald Masterson Gift Fund FX This study was supported by the Diane and Donald Masterson Gift Fund. NR 47 TC 15 Z9 15 U1 3 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUN PY 2011 VL 43 IS 6 BP 1106 EP 1113 DI 10.1249/MSS.0b013e3182061b49 PG 8 WC Sport Sciences SC Sport Sciences GA 764TW UT WOS:000290657300025 PM 21085031 ER PT J AU Paust, S von Andrian, UH AF Paust, Silke von Andrian, Ulrich H. TI Natural killer cell memory SO NATURE IMMUNOLOGY LA English DT Review ID CHEMOKINE RECEPTOR EXPRESSION; IMMUNOGLOBULIN-LIKE RECEPTORS; MOUSE LYMPHOID-CELLS; COMPLEX CLASS-I; T-CELLS; NK CELLS; RHEUMATOID-ARTHRITIS; DENDRITIC CELLS; IFN-GAMMA; CYTOTOXIC REACTIVITY AB Natural killer (NK) cells are bone marrow-derived granular lymphocytes that have a key role in immune defense against viral and bacterial infections and malignancies. NK cells are traditionally defined as cells of the innate immune response because they lack RAG recombinase-dependent clonal antigen receptors. However, evidence suggests that specific subsets of mouse NK cells can nevertheless develop long-lived and highly specific memory to a variety of antigens. Here we review published evidence of NK cell-mediated, RAG-independent adaptive immunity. We also compare and contrast candidate mechanisms for mammalian NK cell memory and antigen recognition with other examples of RAG-independent pathways that generate antigen receptor diversity in non-mammalian species and discuss NK cell memory in the context of lymphocyte evolution. C1 [Paust, Silke; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Paust, Silke] MGH, Ragon Inst, MIT, Charlestown, MA USA. [von Andrian, Ulrich H.] Immune Dis Inst, Boston, MA USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM uva@hms.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU Cancer Research Institute; Ragon Institute of MGH, MIT and Harvard; US National Institutes of Health [AI069259, AI072252, AI1078897] FX Supported by the Cancer Research Institute (S.P.), the Ragon Institute of MGH, MIT and Harvard (S.P. and U.H.v.A.) and the US National Institutes of Health (AI069259, AI072252 and AI1078897 to U.H.v.A.). NR 106 TC 102 Z9 106 U1 2 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUN PY 2011 VL 12 IS 6 BP 500 EP 508 DI 10.1038/ni.2032 PG 9 WC Immunology SC Immunology GA 765LI UT WOS:000290707100008 PM 21739673 ER PT J AU Ise, W Kohyama, M Schraml, BU Zhang, TT Schwer, B Basu, U Alt, FW Tang, J Oltz, EM Murphy, TL Murphy, KM AF Ise, Wataru Kohyama, Masako Schraml, Barbara U. Zhang, Tingting Schwer, Bjoern Basu, Uttiya Alt, Frederick W. Tang, Jun Oltz, Eugene M. Murphy, Theresa L. Murphy, Kenneth M. TI The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells SO NATURE IMMUNOLOGY LA English DT Article ID FOLLICULAR-HELPER-CELLS; NEGATIVE REGULATOR; DENDRITIC CELLS; GENE-REGULATION; C-MAF; DIFFERENTIATION; EXPRESSION; PROMOTER; DIVISION; IL-21 AB The transcription factor BATF controls the differentiation of interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) by regulating expression of the transcription factor ROR gamma t itself and ROR gamma t target genes such as Il17. Here we report the mechanism by which BATF controls in vivo class-switch recombination (CSR). In T cells, BATF directly controlled expression of the transcription factors Bcl-6 and c-Maf, both of which are needed for development of follicular helper T cells (T(FH) cells). Restoring T(FH) cell activity to Batf(-/-) T cells in vivo required coexpression of Bcl-6 and c-Maf. In B cells, BATF directly controlled the expression of both activation-induced cytidine deaminase (AID) and of germline transcripts of the intervening heavy-chain region and constant heavy-chain region (I(H)-C(H)). Thus, BATF functions at multiple hierarchical levels in two cell types to globally regulate switched antibody responses in vivo. C1 [Ise, Wataru; Kohyama, Masako; Schraml, Barbara U.; Tang, Jun; Oltz, Eugene M.; Murphy, Theresa L.; Murphy, Kenneth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. [Ise, Wataru; Kohyama, Masako; Zhang, Tingting; Schwer, Bjoern; Basu, Uttiya; Alt, Frederick W.; Murphy, Kenneth M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. [Zhang, Tingting; Schwer, Bjoern; Basu, Uttiya; Alt, Frederick W.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Zhang, Tingting; Schwer, Bjoern; Basu, Uttiya; Alt, Frederick W.] Harvard Univ, Sch Med, Boston, MA USA. RP Murphy, KM (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. EM kmurphy@wustl.edu FU Howard Hughes Medical Institute FX We thank T. Honjo (Kyoto University) for Aicda-/- mice; and D. Bhattacharya (Washington University) for retroviruses Bcl-6-GFP RV and CD40L-GFP RV. Supported by the Howard Hughes Medical Institute (K.M.M.). NR 41 TC 136 Z9 139 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUN PY 2011 VL 12 IS 6 BP 536 EP U245 DI 10.1038/ni.2037 PG 10 WC Immunology SC Immunology GA 765LI UT WOS:000290707100014 PM 21572431 ER PT J AU Tambe, DT Hardin, CC Angelini, TE Rajendran, K Park, CY Serra-Picamal, X Zhou, EHH Zaman, MH Butler, JP Weitz, DA Fredberg, JJ Trepat, X AF Tambe, Dhananjay T. Hardin, C. Corey Angelini, Thomas E. Rajendran, Kavitha Park, Chan Young Serra-Picamal, Xavier Zhou, Enhua H. Zaman, Muhammad H. Butler, James P. Weitz, David A. Fredberg, Jeffrey J. Trepat, Xavier TI Collective cell guidance by cooperative intercellular forces SO NATURE MATERIALS LA English DT Article ID GLASS-TRANSITION; FOCAL ADHESIONS; SHEET MIGRATION; DYNAMICS; TENSION; MORPHOGENESIS; MALIGNANCY; MECHANICS; JUNCTIONS; CANCER AB Cells comprising a tissue migrate as part of a collective. How collective processes are coordinated over large multi-cellular assemblies has remained unclear, however, because mechanical stresses exerted at cell-cell junctions have not been accessible experimentally. We report here maps of these stresses within and between cells comprising a monolayer. Within the cell sheet there arise unanticipated fluctuations of mechanical stress that are severe, emerge spontaneously, and ripple across the monolayer. Within that stress landscape, local cellular migrations follow local orientations of maximal principal stress. Migrations of both endothelial and epithelial monolayers conform to this behaviour, as do breast cancer cell lines before but not after the epithelial-mesenchymal transition. Collective migration in these diverse systems is seen to be governed by a simple but unifying physiological principle: neighbouring cells join forces to transmit appreciable normal stress across the cell-cell junction, but migrate along orientations of minimal intercellular shear stress. C1 [Tambe, Dhananjay T.; Rajendran, Kavitha; Park, Chan Young; Zhou, Enhua H.; Butler, James P.; Fredberg, Jeffrey J.] Harvard Univ, Sch Publ Hlth, Program Mol & Integrat Physiol Sci, Boston, MA 02115 USA. [Hardin, C. Corey] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Angelini, Thomas E.; Weitz, David A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Serra-Picamal, Xavier; Trepat, Xavier] Univ Barcelona, Inst Bioengn Catalonia, Barcelona 08036, Spain. [Serra-Picamal, Xavier; Trepat, Xavier] Inst Catalana Recerca & Estudis Avancats, Catalana 08036, Spain. [Zaman, Muhammad H.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Fredberg, JJ (reprint author), Harvard Univ, Sch Publ Hlth, Program Mol & Integrat Physiol Sci, 665 Huntington Ave, Boston, MA 02115 USA. EM jfredber@hsph.harvard.edu; xtrepat@ub.edu RI Tambe, Dhananjay/E-3511-2010; Trepat, Xavier/I-3912-2015 OI Trepat, Xavier/0000-0002-7621-5214 FU European Research Council [FP7/ERC-242993]; Spanish Ministry of Science and Innovation [BFU2009-07595]; National Institutes of Health [R01HL102373, R01HL107561, R01CA132633] FX For their critical comments, we thank R. Hubmayr (Mayo Clinic), R. Phillips (CalTech), D. Navajas (University of Barcelona), L. B. Freund (Brown University), D. Tschumperlin (Harvard University), C. Forbes Dewey, Jr (MIT) and V. B. Shenoy (Brown University). We acknowledge the support of the European Research Council (Starting Grant FP7/ERC-242993), the Spanish Ministry of Science and Innovation (BFU2009-07595) and the National Institutes of Health (R01HL102373, R01HL107561, R01CA132633). We thank D. Yu (MDACC) for the kind gift of MCF-10A cell lines. NR 43 TC 252 Z9 252 U1 16 U2 134 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1476-1122 EI 1476-4660 J9 NAT MATER JI Nat. Mater. PD JUN PY 2011 VL 10 IS 6 BP 469 EP 475 DI 10.1038/NMAT3025 PG 7 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Materials Science; Physics GA 767KI UT WOS:000290855100023 PM 21602808 ER PT J AU Gagnon, L Perdue, K Greve, DN Goldenholz, D Kaskhedikar, G Boas, DA AF Gagnon, Louis Perdue, Katherine Greve, Douglas N. Goldenholz, Daniel Kaskhedikar, Gayatri Boas, David A. TI Improved recovery of the hemodynamic response in diffuse optical imaging using short optode separations and state-space modeling SO NEUROIMAGE LA English DT Article DE Diffuse optical imaging; Hemodynamic response; Multidistance measurements; Adaptive filtering; Kalman filtering ID NEAR-INFRARED SPECTROSCOPY; CEREBRAL OXYGEN-METABOLISM; BRAIN ACTIVATION; HUMAN ADULTS; TOMOGRAPHY; NIRS; MOTOR; BOLD; FMRI AB Diffuse optical imaging (DOI) allows the recovery of the hemodynamic response associated with evoked brain activity. The signal is contaminated with systemic physiological interference which occurs in the superficial layers of the head as well as in the brain tissue. The back-reflection geometry of the measurement makes the DOI signal strongly contaminated by systemic interference occurring in the superficial layers. A recent development has been the use of signals from small source-detector separation (1 cm) optodes as regressors. Since those additional measurements are mainly sensitive to superficial layers in adult humans, they help in removing the systemic interference present in longer separation measurements (3 cm). Encouraged by those findings, we developed a dynamic estimation procedure to remove global interference using small optode separations and to estimate simultaneously the hemodynamic response. The algorithm was tested by recovering a simulated synthetic hemodynamic response added over baseline DOI data acquired from 6 human subjects at rest. The performance of the algorithm was quantified by the Pearson R-2 coefficient and the mean square error (MSE) between the recovered and the simulated hemodynamic responses. Our dynamic estimator was also compared with a static estimator and the traditional adaptive filtering method. We observed a significant improvement (two-tailed paired t-test, p < 0.05) in both HbO and HbR recovery using our Kalman filter dynamic estimator compared to the traditional adaptive filter, the static estimator and the standard GLM technique. (C) 2011 Elsevier Inc. All rights reserved. C1 [Gagnon, Louis; Perdue, Katherine; Greve, Douglas N.; Goldenholz, Daniel; Kaskhedikar, Gayatri; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA. [Gagnon, Louis; Boas, David A.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gagnon, Louis] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Perdue, Katherine] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Gagnon, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA. EM lgagnon@nmr.mgh.harvard.edu RI Perdue, Katherine/D-4306-2013; OI Perdue, Katherine/0000-0003-2846-3149; Goldenholz, Daniel/0000-0002-8370-2758 FU NIH [P41-RR14075, R01-EB006385]; Fonds Quebecois sur la Nature et les Technologies; IDEA at MIT FX This work was supported by NIH grants P41-RR14075 and R01-EB006385. L. Gagnon was supported by the Fonds Quebecois sur la Nature et les Technologies and by the IDEA-squared program at MIT. We acknowledge fruitful discussions with Sol Diamond, Emery Brown, Patrick Purdon, Lino Becerra and Dana Brooks. We would also like to thank Michele Desjardins for critical reading of the manuscript. NR 46 TC 70 Z9 70 U1 2 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN 1 PY 2011 VL 56 IS 3 BP 1362 EP 1371 DI 10.1016/j.neuroimage.2011.03.001 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 764RF UT WOS:000290649300049 PM 21385616 ER PT J AU Lord, LD Allen, P Expert, P Howes, O Lambiotte, R McGuire, P Bose, SK Hyde, S Turkheimer, FE AF Lord, Louis-David Allen, Paul Expert, Paul Howes, Oliver Lambiotte, Renaud McGuire, Philip Bose, Subrata K. Hyde, Samuel Turkheimer, Federico E. TI Characterization of the anterior cingulate's role in the at-risk mental state using graph theory SO NEUROIMAGE LA English DT Article ID SMALL-WORLD NETWORKS; FUNCTIONAL CONNECTIVITY; VERBAL FLUENCY; 1ST-EPISODE SCHIZOPHRENIA; BRAIN CONNECTIVITY; PREFRONTAL CORTEX; WORKING-MEMORY; 1ST EPISODE; PSYCHOSIS; ABNORMALITIES AB The onset of positive symptoms in schizophrenia is often preceded by a prodromal phase characterized by neurocognitive abnormalities as well as changes in brain structure and function. Increasing efforts have been made to identify individuals at elevated risk of developing schizophrenia, as early intervention may help prevent progression towards psychosis. The present study uses functional MRI and graph theoretical analysis to characterize the organization of a functional brain network in at-risk mental state patients with varying symptoms assessed with the PANSS and healthy volunteers during performance of a verbal fluency task known to recruit frontal lobe networks and to be impaired in psychosis. We first examined between-groups differences in total network connectivity and global network compactness/efficiency. We then addressed the role of specific brain regions in the network organization by calculating the node-specific "betweeness centrality", "degree centrality" and "local average path length" metrics: different ways of assessing a region's importance in a network. We focused our analysis on the anterior cingulate cortex (ACC): a region known to support executive function that is structurally and functionally impaired in at-risk mental state patients. Although global network connectivity and efficiency were maintained in at-risk patients relative to the controls, we report a significant decrease in the contribution of the ACC to task-relevant network organization in at risk subjects with elevated symptoms (PANSS 45) relative to both the controls and the less symptomatic at-risk subjects, as reflected by a reduction in the topological centrality of the ACC. These findings provide evidence of network abnormalities and anterior cingulate cortex dysfunction in people with prodromal signs of schizophrenia. (C) 2011 Elsevier Inc. Alrrights reserved. C1 [Lord, Louis-David; Howes, Oliver; Turkheimer, Federico E.] Univ London Imperial Coll Sci Technol & Med, Dept Expt Med, London, England. [Allen, Paul; Howes, Oliver; McGuire, Philip] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Expert, Paul; Lambiotte, Renaud] Univ London Imperial Coll Sci Technol & Med, Inst Math Sci, London, England. [Howes, Oliver; Bose, Subrata K.; Turkheimer, Federico E.] Hammersmith Hosp, MRC, Ctr Clin Sci, London, England. [Lord, Louis-David; Hyde, Samuel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula Martinos Ctr Biomed Imaging, Boston, MA USA. RP Lord, LD (reprint author), 2 Hawthorne Pl,Suite 5B, Boston, MA 02114 USA. EM LDL@nmr.mgh.harvard.edu RI Lambiotte, Renaud/C-1085-2009; Turkheimer, Federico/B-9485-2012; Expert, Paul/E-7697-2012; Howes, Oliver/E-7156-2010; OI Lambiotte, Renaud/0000-0002-0583-4595; Turkheimer, Federico/0000-0002-3766-3815; Howes, Oliver/0000-0002-2928-1972; Allen, Paul/0000-0001-8510-878X FU EPSRC [EP/E049451/1]; MRC [U.1200.04.007.00001.01] FX the project has been funded in part by the EPSRC grant EP/E049451/1 and MRC grant U.1200.04.007.00001.01. NR 55 TC 30 Z9 31 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN 1 PY 2011 VL 56 IS 3 BP 1531 EP 1539 DI 10.1016/j.neuroimage.2011.02.012 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 764RF UT WOS:000290649300066 PM 21316462 ER PT J AU Celone, KA Thompson-Brenner, H Ross, RS Pratt, EM Stern, CE AF Celone, Kim A. Thompson-Brenner, Heather Ross, Robert S. Pratt, Elizabeth M. Stern, Chantal E. TI An fMRI investigation of the fronto-striatal learning system in women who exhibit eating disorder behaviors SO NEUROIMAGE LA English DT Article DE Eating disorders; fMRI; Fronto-striatal system; Weather prediction task; Bulimia nervosa; Memory system interactions ID MEDIAL TEMPORAL-LOBE; BULIMIA-NERVOSA; MEMORY-SYSTEMS; PARKINSONS-DISEASE; NEURONAL-ACTIVITY; ANOREXIA-NERVOSA; COGNITIVE SKILL; FUNCTIONAL MRI; BASAL GANGLIA; HUMAN BRAIN AB In the present study, we sought to examine whether the fronto-striatal learning system, which has been implicated in bulimia nervosa, would demonstrate altered BOLD activity during probabilistic category learning in women who met subthreshold criteria for bulimia nervosa (Sub-BN). Sub-BN, which falls within the clinical category of Eating Disorder Not Otherwise Specified (EDNOS). is comprised of individuals who demonstrate recurrent binge eating, efforts to minimize their caloric intake and caloric retention, and elevated levels of concern about shape, weight, and/or eating, but just fail to meet the diagnostic threshold for bulimia nervosa (BN). fMRI data were collected from eighteen women with subthreshold-BN (Sub-BN) and nineteen healthy control women group-matched for age, education and body mass index (MC) during the weather prediction task. Sub-BN participants demonstrated increased caudate nucleus and dorsolateral prefrontal cortex (DLPFC) activation during the learning of probabilistic categories. Though the two subject groups did not differ in behavioral performance, over the course of learning, Sub-BN participants showed a dynamic pattern of brain activity differences when compared to matched control participants. Regions implicated in episodic memory, including the medial temporal lobe (MTL), retrosplenial cortex, middle frontal gyrus, and anterior and posterior cingulate cortex showed decreased activity in the Sub-BN participants compared to MCs during early learning which was followed by increased involvement of the DLPFC during later learning. These findings demonstrate that women with Sub-BN demonstrate differences in fronto-striatal learning system activity, as well as a distinct functional pattern between fronto-striatal and MTL learning systems during the course of implicit probabilistic category learning. (C) 2011 Elsevier Inc. All rights reserved. C1 [Celone, Kim A.; Thompson-Brenner, Heather; Ross, Robert S.; Pratt, Elizabeth M.; Stern, Chantal E.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Celone, Kim A.; Ross, Robert S.; Stern, Chantal E.] Boston Univ, Silvio O Conte Ctr Memory & Brain, Boston, MA 02215 USA. [Celone, Kim A.; Ross, Robert S.; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Thompson-Brenner, Heather; Pratt, Elizabeth M.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Stern, Chantal E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Celone, KA (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington St,Rm 109, Boston, MA 02143 USA. EM kcelone@bu.edu OI Ross, Robert/0000-0002-3987-881X FU Boston University Department of Psychology; National Center for Research Resources [P41RR14075] FX This research was supported by the Boston University Department of Psychology, and National Center for Research Resources (P41RR14075). We thank Dr. Russell Poldrack and Dr. Karin Foerde for providing their weather prediction task experimental design, as well as Jessica Saurman for her help with participant recruitment. We also thank Mary Foley, Larry White, and the Martinos Center staff for assistance with magnetic resonance imaging data collection. NR 51 TC 11 Z9 12 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN 1 PY 2011 VL 56 IS 3 BP 1749 EP 1757 DI 10.1016/j.neuroimage.2011.03.026 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 764RF UT WOS:000290649300089 PM 21419229 ER PT J AU Geser, F Malunda, JA Hurtig, HI Duda, JE Wenning, GK Gilman, S Low, PA Lee, VMY Trojanowski, JQ AF Geser, F. Malunda, J. A. Hurtig, H. I. Duda, J. E. Wenning, G. K. Gilman, S. Low, P. A. Lee, V. M. -Y. Trojanowski, J. Q. TI TDP-43 pathology occurs infrequently in multiple system atrophy SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE 43-kDa transactive response DNA-binding protein; multiple system atrophy ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; MOTOR-NEURON DISEASE; GROUP EMSA-SG; ALZHEIMERS-DISEASE; CYTOPLASMIC INCLUSIONS; ALPHA-SYNUCLEIN; WHITE-MATTER; DNA-BINDING; DEMENTIA AB Aims and Methods: The alpha-synucleinopathy multiple system atrophy (MSA) and diseases defined by pathological 43-kDa transactive response DNA-binding protein (TDP-43) or fused in sarcoma (FUS) aggregates such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration show overlapping clinico-pathological features. Consequently, we examined MSA for evidence of TDP-43 or FUS pathology utilizing immunohistochemical studies in autopsy material from 29 MSA patients. Results: TDP-43 pathology was generally rare, and there were no FUS lesions. The TDP-43 lesions were located predominantly in medio-temporal lobe and subcortical brain areas and were comprised mainly of dystrophic processes and perivascular (and subpial) lesions. Conclusions: The multisystem clinical symptoms and signs of MSA, and in particular the neurobehavioural/cognitive and pyramidal features, appear not to result from concomitant TDP-43 or FUS pathology, but rather from widespread white matter alpha-synuclein positive glial cytoplasmic inclusions and neurodegeneration in keeping with a primary alpha-synuclein-mediated oligodendrogliopathy. The gliodegenerative disease MSA evidently results from different pathogenetic mechanisms than neurodegenerative diseases linked to pathological TDP-43. C1 [Geser, F.; Malunda, J. A.; Lee, V. M. -Y.; Trojanowski, J. Q.] Univ Penn, Sch Med, HUP, Ctr Neurodegenerat Dis Res,Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Hurtig, H. I.; Duda, J. E.] Univ Penn, Sch Med, Penn Hosp, Dept Neurol, Philadelphia, PA 19104 USA. [Duda, J. E.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Gilman, S.] Univ Michigan, Dept Neurol, Michigan Alzheimers Dis Res Ctr, Ann Arbor, MI USA. [Low, P. A.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Wenning, G. K.] Innsbruck Med Univ, Neurodegenerat Res Lab, Div Clin Neurobiol, Innsbruck, Austria. RP Trojanowski, JQ (reprint author), Univ Penn, Sch Med, HUP, Ctr Neurodegenerat Dis Res,Dept Pathol & Lab Med, Maloney 3rd Floor,36th & Spruce St, Philadelphia, PA 19104 USA. EM trojanow@mail.med.upenn.edu FU National Institutes of Health [AG-10124, AG-17586, NS044233, NS 32352, NS 44233, NS 22352, NS 43364]; Mayo CTSA [UL1 RR24150]; Mayo Funds; Federal Ministry of Education and Science, Vienna, Austria FX This work was funded by grants from the National Institutes of Health (AG-10124, AG-17586 and NS044233, NS 32352, NS 44233, NS 22352, NS 43364), Mayo CTSA (UL1 RR24150) and Mayo Funds. Dr Virginia M.-Y. Lee is the John H. Ware III Chair of Alzheimer's Research and Dr John Q. Trojanowski is the William Maul Measey-Truman G. Schnabel, Jr., MD Professor of Geriatric Medicine and Gerontology. Dr Sid Gilman is the William J. Herdman Distinguished University Professor of Neurology. Dr Gregor K. Wenning is Professor of Neurology and Clinical Neurobiology and he has received a Neuroscience Centre Grant by the Federal Ministry of Education and Science, Vienna, Austria. We thank the families of patients whose generosity made this research possible. We also thank Dr Manuela Neumann for providing us with the anti-phosporylated TDP-43 antibody (S409/410), John Robinson, BS, for the comments on the manuscript, and our colleagues at the Center for Neurodegenerative Disease Research and Department of Psychiatry, University of Pennsylvania School of Medicine, for their technical support and advice, particularly Theresa Schuck, BA, Lauren Stutzbach, BA, Michael Partain, BA and Mfon Umoh. NR 50 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD JUN PY 2011 VL 37 IS 4 BP 358 EP 365 DI 10.1111/j.1365-2990.2010.01136.x PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 763WA UT WOS:000290589200003 PM 20942898 ER PT J AU Cohen, AW Copel, JA Macones, GA Menard, MK Riley, L Saade, GR AF Cohen, Arnold W. Copel, Joshua A. Macones, George A. Menard, M. Kathryn Riley, Laura Saade, George R. TI Unjustified Increase in Cost of Care Resulting From US Food and Drug Administration Approval of Makena (17 alpha-Hydroxyprogesterone Caproate) SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PRETERM DELIVERY; PREVENTION AB U.S. Food and Drug Administration (FDA) approval of 17 alpha-hydroxyprogesterone caproate for the indication of decreasing the risk of preterm delivery in those high-risk patients who previously had spontaneous preterm birth has come at considerable cost to the health care system. Weekly injections provided by compounding pharmacies starting at 16-20 weeks of gestation and continuing until 36 weeks currently cost the health care system $200 to $300 per pregnancy. This cost is significantly less than the costs associated with delivering and caring for preterm children. Makena, by KV Pharmaceutical, the same 17 alpha-hydroxyprogesterone caproate product, is priced at $1,500 per injection, or a projected cost of $30,000 per pregnancy. With approximately 132,000 pregnancies being eligible for treatment annually, this increase in cost of 75-150 times what previously had been paid far exceeds the benefits derived from the FDA-approved Makena when compared with previously available compounded versions of 17 alpha-hydroxyprogesterone caproate. This increased health care cost is not justified at this time. The price barrier to access imposed by KV Pharmaceutical actually could result in an increase in preterm deliveries over current rates. Actions are needed by the FDA, national societies, and the manufacturer to ensure that all high-risk patients continue to get the needed therapy to reduce the number of preterm births. (Obstet Gynecol 2011;117:1408-12) DOI: 10.1097/AOG.0b013e31821c2d75 C1 Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. Yale Univ, Sch Med, New Haven, CT USA. Washington Univ, Sch Med, St Louis, MO USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas Med Branch, Galveston, TX USA. RP Menard, MK (reprint author), CB 7516,3010 Old Clin Bldg, Chapel Hill, NC 27599 USA. EM kmenard@med.unc.edu NR 6 TC 11 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2011 VL 117 IS 6 BP 1408 EP 1410 DI 10.1097/AOG.0b013e31821c2d75 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 768AT UT WOS:000290904200023 PM 21471853 ER PT J AU Lobo, AM Stacy, R Cestari, D Stone, JH Jakobiec, FA Sobrin, L AF Lobo, Ann-Marie Stacy, Rebecca Cestari, Dean Stone, John H. Jakobiec, Frederick A. Sobrin, Lucia TI Optic Nerve Involvement with Panuveitis in Sweet Syndrome SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE infliximab; neuro-Sweet; optic nerve; sweet syndrome ID FEBRILE NEUTROPHILIC DERMATOSIS; DISEASE; MANIFESTATIONS AB Purpose: To report a case of a patient with optic nerve involvement in neuro-Sweet syndrome and review the literature on this systemic disease. Methods: Interventional case report and review of the literature. Results: A 49-year-old man developed an acute exacerbation of bilateral panuveitis and optic disc edema together with symptoms of a papular rash on his forearms, fevers, malaise, and arthalgias. Laboratory findings revealed an aseptic meningitis and neutrophilic leukocytosis. Biopsy of the skin rash demonstrated an intense neutrophilic infiltrate in the dermis consistent with the diagnosis of neuro-Sweet syndrome. The patient continued to require corticosteroids for inflammation control in spite of immunomodulatory therapies, including tumor necrosis factor-alpha inhibitor infliximab. Conclusions: Sweet syndrome can present with optic nerve involvement. Screening for underlying etiologies, including autoimmune disease, malignancy, and offending drugs, is important for targeted therapy. C1 [Lobo, Ann-Marie; Stacy, Rebecca; Cestari, Dean; Jakobiec, Frederick A.; Sobrin, Lucia] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Stone, John H.] Massachusetts Gen Hosp, Dept Rheumatol, Boston, MA 02114 USA. RP Lobo, AM (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Ann-Marie_Lobo@meei.harvard.edu FU NIH [EY16335-02] FX Supported by a Research to Prevent Blindness Career Development Award (L.S.), NIH EY16335-02 (L.S.), and a Harvard Catalyst Program for Faculty Development and Diversity Faculty Fellowship NR 19 TC 5 Z9 6 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD JUN PY 2011 VL 19 IS 3 BP 167 EP 170 DI 10.3109/09273948.2011.560411 PG 4 WC Ophthalmology SC Ophthalmology GA 766DH UT WOS:000290760700004 PM 21595532 ER PT J AU Kolesar, JM Dahlberg, SE Marsh, S McLeod, HL Johnson, DH Keller, SM Schiller, JH AF Kolesar, Jill M. Dahlberg, Suzanne E. Marsh, Sharon McLeod, Howard L. Johnson, David H. Keller, Steven M. Schiller, Joan H. TI The NQO1*2/*2 polymorphism is associated with poor overall survival in patients following resection of stages II and IIIa non-small cell lung cancer SO ONCOLOGY REPORTS LA English DT Article DE lung cancer; NAD(P)H:quinone oxidoreductase 1; polymorphism; p53 ID POSTOPERATIVE ADJUVANT THERAPY; PROTEASOMAL DEGRADATION; PROGNOSTIC-SIGNIFICANCE; RANDOMIZED-TRIAL; ONCOLOGY-GROUP; DT-DIAPHORASE; P53; NQO1; CHEMOSENSITIVITY; CHEMOTHERAPY AB NAD(P)H:quinone oxidoreductase 1 (NQO1), is a cytosolic flavoenzyme that catalyzes the two-electron reduction of quinones into hydroquinones. A polymorphism (NQO1*2) alters enzymatic activity of NQO1 resulting in diminished NQO1 activity. Malignancies with NQO1*2 may be resistant to radiation and chemotherapy with resulting poorer survival. NQO1 allele was evaluated in subjects enrolled in ECOG 3590, a randomized comparison of radiation (RT) vs radiation and chemotherapy with cisplatin/etoposide (RCT) in patients with completely resected stages II and IIIa NSCLC. Overall survival was estimated using the Kaplan-Meier method and compared via the log-rank test. Cox models were used to assess the impact of covariates on outcomes. Among 152 patients with assessable samples, 24 (16%) had NQO1*2. Median follow-up was 139 months. The presence of NQO1*2/*2 was associated with decreased overall survival (OS) (median in the heterozygote/wild-type group 42.3 vs. 33.5 months in the variant group, p=0.04). In a multivariable Cox model, variant NQO1 (HR=1.58, p=0.05), age < 60 (HR=0.67, p=0.04), PS 1 (HR=1.47, p=0.05), cardiovascular disease (HR=1.93, p=0.003) and alkaline phosphatase < 100 mg/ml (HR=0.59, p=0.005) were all significant predictors of OS. NQO1*2/*2 may be an independent predictor of poor overall survival in individuals with resected stages II and IIIa NSCLC. Although the basis for the NQO1 association with decreased survival requires additional evaluation, NQO1 may represent a biomarker for guiding individualized therapy. C1 [Kolesar, Jill M.] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53792 USA. [Kolesar, Jill M.] Univ Wisconsin, Sch Pharm, Madison, WI 53792 USA. [Dahlberg, Suzanne E.] Univ Alberta, Eastern Cooperat Oncol Grp, Edmonton, AB, Canada. [Marsh, Sharon] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McLeod, Howard L.] Univ N Carolina, Chapel Hill, NC USA. [Johnson, David H.] Vanderbilt Univ, Nashville, TN USA. [Keller, Steven M.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Kolesar, JM (reprint author), Univ Wisconsin, Ctr Comprehens Canc K4 554, 600 Highland Ave, Madison, WI 53792 USA. EM jmkolesar@pharmacy.wisc.edu FU NIH Pharmacogenetics Research Network [GM63340]; ACCP; American Cancer Society FX This study was supported by the ACCP Oncology Research Award, the NIH Pharmacogenetics Research Network (GM63340), and the American Cancer Society. NR 26 TC 10 Z9 10 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD JUN PY 2011 VL 25 IS 6 BP 1765 EP 1772 DI 10.3892/or.2011.1249 PG 8 WC Oncology SC Oncology GA 764RI UT WOS:000290649600037 PM 21479364 ER PT J AU Tian, YH Wang, SX Ma, YX Lim, G Kim, H Mao, JR AF Tian, Yinghong Wang, Shuxing Ma, Yuxin Lim, Grewo Kim, Hyangin Mao, Jianren TI Leptin enhances NMDA-induced spinal excitation in rats: A functional link between adipocytokine and neuropathic pain SO PAIN LA English DT Article DE Leptin; NMDA receptor; Neuropathic pain; JAK2/STAT3; Patch-clamp recording; Hyperalgesia; Allodynia ID DORSAL-HORN NEURONS; CENTRAL-NERVOUS-SYSTEM; HIPPOCAMPAL SYNAPTIC PLASTICITY; SUBSTANTIA GELATINOSA NEURONS; LONG-TERM POTENTIATION; GENE-EXPRESSION; RECEPTOR EXPRESSION; PITUITARY-GLAND; SERUM LEPTIN; DB/DB MICE AB Recent studies have shown that leptin (an adipocytokine) played an important role in nociceptive behavior induced by nerve injury, but the cellular mechanism of this action remains unclear. Using the whole-cell patch-clamp recording from rat's spinal cord slices, we showed that superfusion of leptin onto spinal cord slices dose-dependently enhanced N-methyl-D-aspartate (NMDA) receptor-mediated currents in spinal cord lamina II neurons. At the cellular level, the effect of leptin on spinal NMDA-induced currents was mediated through the leptin receptor and the JAK2/STAT3 (but not PI3K or MAPK) pathway, as the leptin effect was abolished in leptin receptor-deficient (db/db) mice and inhibited by a JAK/STAT inhibitor. Moreover, we demonstrated in naive rats that a single intrathecal administration of leptin enhanced spontaneous biting, scratching, and licking behavior induced by intrathecal NMDA and that repeated intrathecal administration of leptin elicited thermal hyperalgesia and mechanical allodynia, which was attenuated by the noncompetitive NMDA receptor antagonist MK-801. Intrathecal leptin also upregulated the expression of NMDA receptors and pSTAT3 within the rat's spinal cord dorsal horn, and intrathecal MK-801 attenuated this leptin effect as well. Our data demonstrate a relationship between leptin and NMDA receptor-mediated spinal neuronal excitation and its functional role in nociceptive behavior. Since leptin contributes to nociceptive behavior induced by nerve injury, the present findings suggest an important cellular link between the leptin's spinal effect and the NMDA receptor-mediated cellular mechanism of neuropathic pain. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Tian, Yinghong; Wang, Shuxing; Ma, Yuxin; Lim, Grewo; Kim, Hyangin; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. [Tian, Yinghong] So Med Univ, Dept Physiol, Guangzhou 510515, Guangdong, Peoples R China. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. EM jmao@partners.org FU National Institutes of Health [P20DA26002, RO1DE18214, RO1DE18538] FX This study was supported by National Institutes of Health Grants P20DA26002, RO1DE18214, and RO1DE18538. NR 68 TC 29 Z9 31 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUN PY 2011 VL 152 IS 6 BP 1263 EP 1271 DI 10.1016/j.pain.2011.01.054 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 765MD UT WOS:000290710100012 PM 21376468 ER PT J AU Kaplan, JL Shi, HN Walker, WA AF Kaplan, Jess L. Shi, Hai Ning Walker, W. Allan TI The Role of Microbes in Developmental Immunologic Programming SO PEDIATRIC RESEARCH LA English DT Review ID PLACEBO-CONTROLLED TRIAL; FORMULA-FED INFANTS; DUST-MITE ALLERGEN; IMMUNE-RESPONSES; CORD BLOOD; IN-UTERO; NECROTIZING ENTEROCOLITIS; INTESTINAL MICROBIOTA; FOLLOW-UP; ATOPIC-DERMATITIS AB The role of microorganisms in the gastrointestinal tract has undergone significant modification in the past few decades with new observations from clinical, epidemiologic, and basic science research. We now know that the perception of these gut microbes as pathogens or even as commensals is somewhat outdated. It is becoming increasingly clear that the gut microbiome plays an important role in a host of activities including digestion, protection from potentially pathogenic organisms, and the regulation and development of the host immune system. The complex interactions between microbes and host combined with recent clinical observations and epidemiologic trends may point to the convergence of two well-supported (though imperfect) hypotheses: the "hygiene hypothesis" and the "fetal programming hypothesis." We are beginning to understand that exposure to microbes before conception, during gestation, and in the neonatal period have profound effects on the developing immune system. Recent observations from a variety of fields help support the expansion of the "fetal programming hypothesis" to a host-microbe corollary that microbe-host interactions at critical windows influence the future immune phenotype, the maintenance of immune health, and the development of immune-mediated disease. (Pediatr Res 69: 465-472, 2011) C1 Harvard Univ, MassGen Hosp Children, Sch Med, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, MassGen Hosp Children, Sch Med, Mucosal Immunol Lab, Boston, MA 02114 USA. RP Walker, WA (reprint author), MassGen Hosp Children, Mucosal Immunol Lab, 114 16th St 114-3503, Charlestown, MA 02129 USA. EM wwalker@partners.org FU NIDDK NIH HHS [R01 DK082427] NR 108 TC 69 Z9 72 U1 3 U2 34 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JUN PY 2011 VL 69 IS 6 BP 465 EP 472 DI 10.1203/PDR.0b013e318217638a PG 8 WC Pediatrics SC Pediatrics GA 767CA UT WOS:000290831700001 PM 21364495 ER PT J AU Hwang, NS Im, SG Wu, PB Bichara, DA Zhao, X Randolph, MA Langer, R Anderson, DG AF Hwang, Nathaniel S. Im, Sung Gap Wu, Patrick B. Bichara, David A. Zhao, Xing Randolph, Mark A. Langer, Robert Anderson, Daniel G. TI Chondrogenic Priming Adipose-Mesenchymal Stem Cells for Cartilage Tissue Regeneration SO PHARMACEUTICAL RESEARCH LA English DT Article DE auricular chondrocytes; cartilage; co-culture; human adipose derived mesenchymal stem cells; tissue engineering ID IN-VIVO; OSTEOGENIC DIFFERENTIATION; MATURE CHONDROCYTES; REPAIR; MONOLAYER; SIGNALS; PROTEIN AB Purpose Chondrocytes lose their ability to produce cartilaginous matrix during multiplication in culture through repeated passages, resulting in inferior tissue phenotype. To overcome the limited amount of primary chondrocytes, we aimed to determine the optimal culture condition for in vitro/in vivo cartilage regeneration using human adipose-derived mesenchymal stem cells (AMSCs). Methods To evaluate the effects exerted by the chondrocytic culture condition on AMSC, we utilized chondrocyte conditioned medium (CM) and/or co-culture methods to prime and differentiate AMSCs. We evaluated ultimate in vivo engineered cartilage with primed AMSCs with that of chondrocytes. To examine the link between conditioned factors and proliferation/differentiation, cell cycle progression of AMSCs were examined using 5-ethynyl-2'-deoxyuridine (EdU), and gene expression was monitored. Results We report that AMSCs can be stimulated to become chondrogenic cells when expanded with chondrocyte CM. Polymeric scaffolds co-seeded with CM-expanded AMSCs and primary chondrocytes resulted in in vivo cartilaginous tissues with similar biochemical content to constructs seeded with chondrocytes alone. Conclusion These results indicate that chondrocyte CM consists of suitable morphogenetic factors that induce the chondrogenic priming of AMSCs for cartilage tissue engineering. C1 [Im, Sung Gap; Langer, Robert; Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Hwang, Nathaniel S.; Wu, Patrick B.; Langer, Robert; Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Im, Sung Gap] Korea Adv Inst Sci & Technol, Dept Chem & Biomol Engn, Taejon 305701, South Korea. [Bichara, David A.; Zhao, Xing; Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA 02114 USA. RP Anderson, DG (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. EM dgander@mit.edu RI Im, Sung Gap/C-1823-2011 OI Im, Sung Gap/0000-0002-2802-6398 FU Armed Forces Institute of Regenerative Medicine [W81XWH-08-2-0034] FX This research was sponsored by the Armed Forces Institute of Regenerative Medicine award number W81XWH-08-2-0034. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. The content of the study does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. NR 39 TC 24 Z9 29 U1 1 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD JUN PY 2011 VL 28 IS 6 BP 1395 EP 1405 DI 10.1007/s11095-011-0445-2 PG 11 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 766RK UT WOS:000290804000015 PM 21494923 ER PT J AU Woodby, LL Williams, BR Wittich, AR Burgio, KL AF Woodby, Lesa L. Williams, Beverly Rosa Wittich, Angelina R. Burgio, Kathryn L. TI Expanding the Notion of Researcher Distress: The Cumulative Effects of Coding SO QUALITATIVE HEALTH RESEARCH LA English DT Article DE coding; data collection and management; emotions / emotion work; end-of-life issues; research, qualitative; risk; stress / distress ID QUALITATIVE HEALTH RESEARCH; METHODOLOGICAL ISSUES; SENSITIVE TOPICS; LAST HOURS; LIFE; INTERVIEW; CANCER; CARE; REFLECTIONS; EXPLORATION AB Qualitative researchers who explore the individual's experience of health, illness, death, and dying often experience emotional stress in their work. In this article, we describe the emotional stress we experienced while coding semistructured, after-death interviews conducted with 38 next of kin of deceased veterans. Coding sensitive topic data required an unexpected level of emotional labor, the impact of which has not been addressed in the literature. In writing this discussion article, we stepped back from our roles as interviewers/coders and reflected on how our work affected us individually and as a team, and how a sequence of exposures could exert a cumulative effect for researchers in such a dual role. Through this article, we hope to generate an expanded discourse on how qualitative inquiry impacts the emotional well-being of researchers. C1 [Woodby, Lesa L.] Birmingham VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Birmingham, AL 35233 USA. RP Woodby, LL (reprint author), Birmingham VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, GRECC 11G,700 S 19th St, Birmingham, AL 35233 USA. EM Lesa.Woodby@va.gov NR 72 TC 18 Z9 19 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD JUN PY 2011 VL 21 IS 6 BP 830 EP 838 DI 10.1177/1049732311402095 PG 9 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 759BH UT WOS:000290214400009 PM 21393618 ER PT J AU Fennessy, FM Kong, CY Tempany, CM Swan, JS AF Fennessy, Fiona M. Kong, Chung Yin Tempany, Clare M. Swan, J. Shannon TI Quality-of-Life Assessment of Fibroid Treatment Options and Outcomes SO RADIOLOGY LA English DT Article ID FOCUSED ULTRASOUND SURGERY; UTERINE ARTERY EMBOLIZATION; COST-EFFECTIVENESS; RHEUMATOID-ARTHRITIS; PROCESS UTILITY; HEALTH; LEIOMYOMAS; DISEASE; HYSTERECTOMY; INSTRUMENTS AB Purpose: To obtain utilities (a unit of measure of a person's relative preferences for different health states compared with death or worst possible outcome) for uterine fibroids before and after treatment and to measure short-term utilities for the following uterine fibroid treatments: abdominal hysterectomy, magnetic resonance (MR) imaging-guided focused ultrasound surgery, and uterine artery embolization (UAE). Materials and Methods: This retrospective study was approved by the institutional review board and was HIPAA compliant. The waiting trade-off (WTO) method, a variation on the time trade-off (TTO) method, is used to obtain utilities for diagnostic procedures on the basis of the fact that people wait longer to avoid noxious tests and/or procedures. The WTO method provides short-term quality of life tolls in terms of quality-adjusted life-weeks by scaling wait times with pre-and posttreatment utilities. Utilities for uterine fibroids before and after treatment were obtained with the TTO method and a visual analog scale (VAS) by using a questionnaire administered by means of a phone interview. WTO wait times were adjusted for quality of life with VAS and TTO utilities and a transformation of VAS. Wait times were compared by using nonparametric tests. The study participants included 62 patients who had undergone abdominal hysterectomy, 74 who had undergone UAE, and 61 who had undergone MR imaging-guided focused ultrasound surgery. Results: Quality of life increased with all treatments. The median WTO wait time was higher for hysterectomy (21.6 weeks) than for UAE or MR imaging-guided focused ultrasound surgery (14.1 weeks for both) (P < .05). Quality-adjusted life-week tolls were smaller when scaled according to TTO than when scaled according to VAS or transformation of VAS. Conclusion: Quality of life increased after all fibroid treatments. WTO is feasible for assessing the quality-adjusted morbidity of treatment procedures. (C) RSNA, 2011 C1 [Fennessy, Fiona M.; Tempany, Clare M.] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Kong, Chung Yin; Swan, J. Shannon] Harvard Univ, Sch Med, Inst Technol Assessment, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fennessy, FM (reprint author), Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM ffennessy@partners.org FU General Electric AUR Radiology Research Academic Fellowship (GERRAF); National Institutes of Health [U41-RR019703]; InSightec FX F.M.F. supported by General Electric AUR Radiology Research Academic Fellowship (GERRAF).; This research was supported in part by the National Institutes of Health (grant U41-RR019703).; F.M.F. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. C. H. K. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. C. M. T. Financial activities related to the present article: receives a consulting fee or honorarium from InSightec; institution received money from InSightec for clinical trial support. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. J.S.S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. NR 40 TC 12 Z9 13 U1 0 U2 3 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 JUN PY 2011 VL 259 IS 3 BP 785 EP 792 DI 10.1148/radiol.11100704 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767ZB UT WOS:000290898100018 PM 21364084 ER PT J AU Deatrick, JA Given, B AF Deatrick, Janet A. Given, Barbara TI Creating a Pipeline for Tomorrow's Nurse Researchers SO RESEARCH IN NURSING & HEALTH LA English DT Editorial Material ID HIGH-SCHOOL-STUDENTS; EDUCATION; RETENTION; PROGRAM C1 [Deatrick, Janet A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Given, Barbara] Michigan State Univ, Coll Nursing, E Lansing, MI 48824 USA. RP Deatrick, JA (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Room 223,Claire M Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. NR 23 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD JUN PY 2011 VL 34 IS 3 BP 171 EP 175 DI 10.1002/nur.20436 PG 5 WC Nursing SC Nursing GA 762EG UT WOS:000290455000002 PM 21520145 ER PT J AU Gould, J Ellsmere, J Fanelli, R Hutter, M Jones, S Pratt, J Schauer, P Schirmer, B Schwaitzberg, S Jones, DB AF Gould, J. Ellsmere, J. Fanelli, R. Hutter, M. Jones, S. Pratt, J. Schauer, P. Schirmer, B. Schwaitzberg, S. Jones, D. B. TI Panel report: best practices for the surgical treatment of obesity SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Bariatric surgery; Weight loss surgery; Patient safety ID WEIGHT-LOSS SURGERY; LAPAROSCOPIC GASTRIC BYPASS; BARIATRIC SURGERY; SLEEP-APNEA; INFORMED-CONSENT; MORBID-OBESITY; RECOMMENDATIONS; ADOLESCENTS; EDUCATION; CHILDREN AB Background Bariatric surgery is a rapidly growing field. Advances in surgical technologies and techniques have raised concerns about patient safety. Bariatric surgeons and programs are under increased scrutiny from regulatory agencies, insurers, and public health officials to provide high quality and safe care for bariatric patients at all phases of care. Methods During the 2009 annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), a panel of experts convened to provide updated information on patient safety and best practices in bariatric surgery. The following article is a summary of this panel presentation. Results and Conclusions Weight loss surgery is a field that is evolving and adapting to multiple external pressures. Safety concerns along with increasing public scrutiny have led to a systematic approach to defining best practices, creating standards of care, and identifying mechanisms to ensure that patients consistently receive the best and most effective care possible. In many ways, bariatric surgery and multidisciplinary bariatric surgery programs may serve as a model for other programs and surgical specialties in the near future. C1 [Gould, J.] Univ Wisconsin, Sch Med, Clin Sci Ctr H4 726, Madison, WI 53792 USA. [Ellsmere, J.] Dalhousie Univ, Div Gen Surg, Halifax, NS, Canada. [Fanelli, R.] Univ Massachusetts, Sch Med, Dept Surg, Worcester, MA USA. [Hutter, M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Jones, S.] Beth Israel Deaconess Med Ctr, Dept Anesthesia, Boston, MA 02215 USA. [Pratt, J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Schauer, P.] Cleveland Clin, Dept Surg, Cleveland, OH 44106 USA. [Schirmer, B.] Univ Virginia, Dept Surg, Charlottesville, VA USA. [Schwaitzberg, S.] Cambridge Hlth Alliance, Dept Surg, Cambridge, MA USA. [Jones, D. B.] Beth Israel Deaconess Med Ctr, Sect Minimally Invas Surg, Boston, MA 02215 USA. RP Gould, J (reprint author), Univ Wisconsin, Sch Med, Clin Sci Ctr H4 726, 600 Highland Ave, Madison, WI 53792 USA. EM gould@surgery.wisc.edu OI Jones, Stephanie/0000-0001-8342-0374 FU Gore; Baxter; Covidien; Allergan; Ethicon; Cinemed FX Dr. Gould serves as a speaker for Covidien. Dr. Ellsmere serves as a consultant for Ethicon. Dr. Fanelli is a consultant and a speaker for Ethicon, is on the surgeon advisory board and provides research support for RTI Biologics, serves on the medical advisory board for Polytouch Medical, is a consultant and provides research support for Bracco Diagnostics, and serves as a consultant and receives a royalty stream from Cook Medical. For New Wave Surgical he is an owner, serves on the Board of Directors, and the Medical Advisory Board. Dr. Pratt serves as a consultant for Covidien and as a Scientific Advisor for Boston Scientific. Dr. Schauer is a consultant, a research grant recipient, and serves on the Scientific Advisory Board for Ethicon. He serves on the Board of Directors for Remedy MD. He has received an Educational Grant and serves on the Scientific Advisory Board for Stryker. He is a consultant, a research grant recipient, and serves on the Scientific Advisory Board for Bard-Davol. He is a consultant and the recipient of a research grant from Gore. He has received an educational grant from Baxter. He serves on the Scientific Advisory Board for Barosense, Surgiquest, and Cardinal/Snowden Pencer. He has received educational grants from Covidien and Allergan. He is also on the Board of Directors for Surgical Excellence LLC. Dr. Schwaitzberg serves as a consultant for Olympus, Stryker, Surgiquest, Cambridge Endoscopy, Endocore, and Acuity Bio. Dr. Daniel Jones serves as a consultant for Olympus, Allergan, Stryker, and Surgiquest; he is the recipient of training grants from Ethicon and Covidien, and he receives book royalties from Cinemed. Drs. Hutter, Stephanie Jones, and Schirmer have no conflicts of interest or financial ties to disclose. NR 41 TC 12 Z9 12 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD JUN PY 2011 VL 25 IS 6 BP 1730 EP 1740 DI 10.1007/s00464-010-1487-y PG 11 WC Surgery SC Surgery GA 766SG UT WOS:000290806200004 PM 21136099 ER PT J AU Batista, LM Carvalho, CH Acioly, MA Gharabaghi, A Ramina, KF Schittenhelm, J Tatagiba, M AF Batista, Leonardo Moura Carvalho, Carlos Henrique Acioly, Marcus Andre Gharabaghi, Alireza Ramina, Kristofer Fingerle Schittenhelm, Jens Tatagiba, Marcos TI Spinal metastasis of endometrial stromal sarcoma: Clinicopathological features and management SO SURGICAL ONCOLOGY-OXFORD LA English DT Review DE Endometrial stromal sarcoma; Metastasis; Thoracic spine; Spinal tumor; Immunohistochemical ID SMOOTH-MUSCLE TUMORS; EXPRESSION; NEOPLASMS; THERAPY; CORD; CD10 AB Background: Endometrial Stromal Sarcoma(ESS) is a rare uterine malignancy which often metastasizes several years after initial diagnosis. Thoracic spine is a rare ESS metastatic site and its proper management is still not a consensus. We discuss the histopathological features and the management strategies through an illustrative case of a 77 year-old woman with metastasis to the thoracic spine 13 years after total hysterectomy for ESS. Methods: Review of the literature and identification of 5 patients, including our present case, with ESS involving the spinal cord. We discuss the outcomes achieved after each therapy. In our case, the patient presented a mass involving the thoracic spinal canal constricting the spinal cord at T7 level. A two-level decompression laminectomy was performed and the lesion was partially excised. Results: The histopathological along with the immunohistochemical profile mitotic rate indicated the endometrial stromal cells origin of the tumor, confirming the diagnosis of a low-grade ESS metastasis. The patient was managed with surgery in combination with postoperative radiation therapy. Conclusions: The small number of published cases precludes definitive conclusions regarding standard management. However, it seems that treatment of metastatic ESS to the spine matches the same general concepts of spine metastasis, namely surgery followed by radiation therapy, due to clinical improvement and long-term disease control of the reported cases. Hormonal therapy may be considered in recurrent disease with strong expression of estrogen and progesterone receptors. However, these findings need confirmation in larger studies. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Batista, Leonardo Moura; Carvalho, Carlos Henrique; Acioly, Marcus Andre; Gharabaghi, Alireza; Ramina, Kristofer Fingerle; Tatagiba, Marcos] Univ Tubingen, Dept Neurosurg, Eberhard Karls Univ Hosp, D-72076 Tubingen, Germany. [Batista, Leonardo Moura] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Boston, MA 02114 USA. [Schittenhelm, Jens] Univ Tubingen, Inst Brain Res, Eberhard Karls Univ Hosp, D-72076 Tubingen, Germany. RP Batista, LM (reprint author), Univ Tubingen, Dept Neurosurg, Eberhard Karls Univ Hosp, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. EM lbatista@nmr.mgh.harvard.edu RI Acioly, Marcus /G-2724-2012 NR 26 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0960-7404 J9 SURG ONCOL JI Surg. Oncol.-Oxf. PD JUN PY 2011 VL 20 IS 2 BP E78 EP E83 DI 10.1016/j.suronc.2010.10.006 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 766BZ UT WOS:000290756000003 PM 21071207 ER PT J AU Ozhathil, DK Abar, B Baumann, BM Camargo, CA Ziedonis, D Boudreaux, ED AF Ozhathil, Deepak K. Abar, Beau Baumann, Brigitte M. Camargo, Carlos A., Jr. Ziedonis, Douglas Boudreaux, Edwin D. TI The Effect of Removing Cost as a Barrier to Treatment Initiation With Outpatient Tobacco Dependence Clinics Among Emergency Department Patients SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID SMOKING; INTERVENTION AB Objectives: The campaign against tobacco addiction and smoking continues to play an important role in public health. However, referrals to outpatient tobacco cessation programs by emergency physicians are rarely pursued by patients following discharge. This study explored cost as a barrier to follow-up. Methods: The study was performed at a large urban hospital emergency department (ED) in Camden, New Jersey. Enrollment included adults who reported tobacco use in the past 30 days. Study participants were informed about a "Stop Smoking Clinic" affiliated with the hospital and, depending on enrollment date, cost of treatment was advertised as $150 (standard fee), $20 (reduced fee), or $0 (no fee). Monitoring of patient inquiries and visits to the clinic was performed for 6 months following enrollment of the last study subject. Results: The analyzed sample consisted of 577 tobacco users. There were no statistically significant demographic differences between treatment groups (p > 0.05). Two-hundred forty-seven (43%) participants reported "very much" interest in smoking cessation. However, there was no significant difference in initiating treatment with the Stop Smoking Clinic across experimental condition. Only a single subject, enrolled in the no-fee phase, initiated treatment with the clinic. Conclusions: Cost is unlikely to be the only barrier to pursing outpatient tobacco treatment after an ED visit. Further research is needed to determine the critical components of counseling and referral that maximize postdischarge treatment initiation. ACADEMIC EMERGENCY MEDICINE 2011; 18:662-664 (C) 2011 by the Society for Academic Emergency Medicine C1 [Ozhathil, Deepak K.; Abar, Beau; Ziedonis, Douglas; Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Worcester, MA 01610 USA. [Baumann, Brigitte M.] Cooper Univ Hosp, Camden, NJ USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. RP Boudreaux, ED (reprint author), Univ Massachusetts, Sch Med, Worcester, MA 01610 USA. EM edwin.boudreaux@umassmed.edu OI Boudreaux, Edwin/0000-0002-3223-6371 FU NIH/NIDA [K23DA16698] FX This study was supported by a NIH/NIDA K23 Research Career Award (EDB) (K23DA16698). NR 10 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 2011 VL 18 IS 6 BP 662 EP 664 DI 10.1111/j.1553-2712.2011.01048.x PG 3 WC Emergency Medicine SC Emergency Medicine GA 781BP UT WOS:000291905900014 PM 21518096 ER PT J AU Taylor, DM Balabadra, U Xiang, ZM Woodman, B Meade, S Amore, A Maxwell, MM Reeves, S Bates, GP Luthi-Carter, R Lowden, PAS Kazantsev, AG AF Taylor, David M. Balabadra, Uma Xiang, Zhongmin Woodman, Ben Meade, Sarah Amore, Allison Maxwell, Michele M. Reeves, Steven Bates, Gillian P. Luthi-Carter, Ruth Lowden, Philip A. S. Kazantsev, Aleksey G. TI A Brain-Permeable Small Molecule Reduces Neuronal Cholesterol by Inhibiting Activity of Sirtuin 2 Deacetylase SO ACS CHEMICAL BIOLOGY LA English DT Article ID HUNTINGTONS-DISEASE; MODELS AB Sirtuin 2 (SIRT2) deacetylase-dependent inhibition mediates neuroprotective reduction of cholesterol biosynthesis in an in vitro Huntington's disease model. This study sought to identify the first brain permeable SIRT2 inhibitor and to characterize its cholesterol-reducing properties in neuronal models. Using biochemical sirtuin deacetylation assays, we screened a brain-permeable in silico compound library, yielding 3-(1-azepanyl-sulfonyl)-N-(3-bromphenyl)benzamide as the most potent and selective SIRT2 inhibitor. Pharmacokinetic studies demonstrated brain-permeability but limited metabolic stability of the selected candidate. In accordance with previous observations, this SIRT2 inhibitor stimulated cytoplasmic retention of sterol regulatory element binding protein-2 and subsequent transcriptional down-regulation of cholesterol biosynthesis genes, resulting in reduced total cholesterol in primary striatal neurons. Furthermore, the identified inhibitor reduced cholesterol in cultured naive neuronal cells and brain slices from wild-type mice. The outcome of this study provides a clear opportunity for lead optimization and drug development, targeting metabolic dysfunctions in CNS disorders where abnormal cholesterol homeostasis is implicated. C1 [Xiang, Zhongmin; Meade, Sarah; Amore, Allison; Maxwell, Michele M.; Reeves, Steven; Kazantsev, Aleksey G.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Taylor, David M.; Luthi-Carter, Ruth] Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland. [Balabadra, Uma; Lowden, Philip A. S.] Univ London, Dept Biol Sci, London WC1E 7HX, England. [Woodman, Ben; Bates, Gillian P.] Guys Hosp, Kings Coll London, Dept Med & Mol Genet, London SE1 9RT, England. [Maxwell, Michele M.; Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Kazantsev, AG (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. EM akazantsev@partners.org RI Bates, Gillian/E-1146-2012 OI Bates, Gillian/0000-0002-4041-6305 FU Carmen Foundation; RJG Foundation; Michael J. Fox Foundation for Parkinson's Research; CHDI Foundation; Ecole Polytechnique Federale de Lausanne; Swiss National Science Foundation FX We thank M. Forrest and L. Feletti for help with culture preparation. This work was supported by the Carmen Foundation, the RJG Foundation, the Michael J. Fox Foundation for Parkinson's Research, the CHDI Foundation, the Ecole Polytechnique Federale de Lausanne, and the Swiss National Science Foundation. NR 18 TC 50 Z9 51 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JUN PY 2011 VL 6 IS 6 BP 540 EP 546 DI 10.1021/cb100376q PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 780YD UT WOS:000291896400003 PM 21370928 ER PT J AU Campbell, GR Watkins, JD Loret, EP Spector, SA AF Campbell, Grant R. Watkins, Jennifer D. Loret, Erwann P. Spector, Stephen A. TI Differential Induction of Rat Neuronal Excitotoxic Cell Death by Human Immunodeficiency Virus Type 1 Clade B and C Tat Proteins SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HIV-1 TAT; STRUCTURAL-CHARACTERIZATION; HOMONUCLEAR H-1-NMR; CEREBROSPINAL-FLUID; RICH REGION; T-CELLS; ZINC; APOPTOSIS; BRAIN; INFECTION AB In the absence of effective antiretroviral therapy, infection with clade B human immunodeficiency virus (HIV-1) infection commonly progresses to AIDS dementia. However, in India, where clade C infection is most prevalent, severe cognitive impairment due to HIV-1 is reported to be less prevalent. The Tat protein of HIV-1, which is released from HIV-1-infected macrophages, is thought to play a major role in the disruption of neuronal function as well as in the infiltration of macrophages associated with advanced neuropathogenesis. Clade B Tat is excitotoxic to hippocampal neurons by potentiating N-methyl-D-aspartate-induced currents of the zinc-sensitive NR1/NR2A N-methyl-D-aspartate receptor in a zinc-binding-dependent mechanism. This study characterizes the zinc-binding properties of clade C Tat protein. Using ultraviolet spectroscopy and the Ellman reaction, we show that clade C Tat protein binds just one zinc ion per monomer. We then investigated the ability of clade C Tat to block the inhibition of N-methyl-D-aspartate receptors from zinc antagonism through ion chelation. Although clade C Tat enhanced N-methyl-D-aspartate-mediated rat hippocampus neuronal toxicity in the presence of zinc, the increase was significantly less than that observed with clade B Tat. These findings suggest that the observed differences in neuropathogenesis found with HIV-1 clade C infection compared to clade B may, in part, be due to a decrease in Tat-mediated neurotoxicity. C1 [Campbell, Grant R.; Spector, Stephen A.] Univ Calif San Diego, Div Infect Dis, Dept Pediat, La Jolla, CA 92093 USA. [Watkins, Jennifer D.; Loret, Erwann P.] Univ Aix Marseille 2, Fac Pharm, Equipe Technol Rech Appl VIH 1 2011, Marseille, France. [Watkins, Jennifer D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Spector, Stephen A.] Rady Childrens Hosp, San Diego, CA USA. RP Spector, SA (reprint author), Univ Calif San Diego, Div Infect Dis, Dept Pediat, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM saspector@ucsd.edu OI Campbell, Grant/0000-0003-3927-1994 FU National Institute of Allergy and Infectious Diseases (NIAID) of the United States National Institutes of Health (NIH) [U01 AI068632] FX This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the United States National Institutes of Health (NIH) Grant U01 AI068632 to the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT). NR 52 TC 11 Z9 11 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 2011 VL 27 IS 6 BP 647 EP 654 DI 10.1089/aid.2010.0192 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 769LJ UT WOS:000291014700009 PM 20977378 ER PT J AU Simpson, T Rosenthal, C Gurrad, B Luterek, J Kaysen, D AF Simpson, Tracy Rosenthal, Christina Gurrad, Bethann Luterek, Jane Kaysen, Debra TI A PILOT STUDY EVALUATING MECHANISMS OF CHANGE AMONG PATIENTS WITH COMORBID PTSD AND ALCOHOL DEPENDENCE: METHODS AND FEASIBILITY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Simpson, Tracy; Rosenthal, Christina; Gurrad, Bethann; Luterek, Jane; Kaysen, Debra] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 142A EP 142A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301023 ER PT J AU van Doorn, H van Hoffen, E Jager, SH Knulst, A Shreffler, W Knol, K AF van Doorn, H. van Hoffen, E. Jager, Hartog S. Knulst, A. Shreffler, W. Knol, K. TI Peanut allergen Ara h 6 is the most potent peanut allergen in basophil activation SO ALLERGY LA English DT Meeting Abstract CT 30th Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 11-15, 2011 CL Istanbul, TURKEY SP European Acad Allergy & Clin Immunol (EAACI) C1 [van Doorn, H.; van Hoffen, E.; Jager, Hartog S.; Knulst, A.; Knol, K.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Shreffler, W.] Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD JUN PY 2011 VL 66 SU 94 SI SI MA 203 BP 98 EP 98 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 286IS UT WOS:000329462200204 ER PT J AU Cernadas, J Santos, N Pinto, C Castells, M AF Cernadas, J. Santos, N. Pinto, C. Castells, M. TI Hypersensitivity reaction and tolerance induction to ethambutol SO ALLERGY LA English DT Meeting Abstract CT 30th Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 11-15, 2011 CL Istanbul, TURKEY SP European Acad Allergy & Clin Immunol (EAACI) C1 [Cernadas, J.; Santos, N.] Hosp Sao Joao, EPE, Serv Imunoalergol, Oporto, Portugal. [Castells, M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD JUN PY 2011 VL 66 SU 94 SI SI MA 985 BP 381 EP 381 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 286IS UT WOS:000329462202168 ER PT J AU Craig, T Riedl, M Riedl, M Baker, J Banerji, A Hurewitz, D Kalfus, I Tillotson, G AF Craig, T. Riedl, M. Riedl, M. Baker, J. Banerji, A. Hurewitz, D. Kalfus, I Tillotson, G. TI Open-label use of nanofiltered C1 esterase inhibitor (human) for treatment or prophylaxis of acute attacks of hereditary angioedema in pregnant subjects SO ALLERGY LA English DT Meeting Abstract CT 30th Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 11-15, 2011 CL Istanbul, TURKEY SP European Acad Allergy & Clin Immunol (EAACI) C1 [Craig, T.] Penn State Univ, Hershey, PA USA. [Riedl, M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Baker, J.] Allergy Asthma & Dermatol Res Ctr, Lake Oswego, OR USA. [Banerji, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hurewitz, D.] Allergy Clin Tulsa, Tulsa, OK USA. [Kalfus, I; Tillotson, G.] Viropharma Inc, Exton, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD JUN PY 2011 VL 66 SU 94 SI SI MA 1089 BP 419 EP 419 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 286IS UT WOS:000329462202272 ER PT J AU Gold, NB Westgate, MN Holmes, LB AF Gold, Nina B. Westgate, Marie-Noel Holmes, Lewis B. TI Anatomic and Etiological Classification of Congenital Limb Deficiencies SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE classification; congenital anomalies; limb reduction defect ID HOLT-ORAM-SYNDROME; FANCONI-ANEMIA; 1ST TRIMESTER; DEFECTS; MALFORMATIONS; MUTATIONS; DAUGHTER; HYPOPLASIA; DIAGNOSIS; EXPOSURE AB Limb deficiencies, the congenital absence or hypoplasia of a long bone and/or digits, vary greatly in their anatomy and etiology. Previous attempts to classify the range of possible phenotypes have not included all types of deficiencies. We present a new classification system, which includes all potential phenotypes. Infants with limb deficiencies were identified in the hospital-based Active Malformations Surveillance Program at Brigham and Women's Hospital in Boston, MA from the years 1972 to 1974 and 1979 to 2000. Affected infants were classified based on the anatomy and apparent cause of their deficiencies. The prevalence rate of all types of limb deficiency was 0.79/1,000. Upper limb deficiencies were significantly more common than lower limb deficiencies. There was no significant difference in frequencies between deficiencies on the left and right sides of the body. Longitudinal defects were more common than terminal transverse defects; intercalary defects were uncommon. Longitudinal defects were most likely to occur on the preaxial side of the limb. Almost half of affected infants had affected digits, with normal long bones. The most common apparent cause of limb deficiencies was vascular disruption defects (0.22/1,000), such as amniotic band-related limb deficiency. This new classification system includes deficiency of each long bone, as well as absence of any finger or toe. This system will make it possible to establish the prevalence of each specific phenotype. The large number of distinct apparent causes illustrates the marked etiologic heterogeneity of limb deficiencies. (C) 2011 Wiley-Liss, Inc. C1 [Holmes, Lewis B.] Brigham & Womens Hosp, Dept Newborn Med, Teratol Unit, Act Malformat Surveillance Program, Boston, MA 02115 USA. [Gold, Nina B.; Westgate, Marie-Noel; Holmes, Lewis B.] MassGen Hosp Children, Genet Unit, Boston, MA USA. RP Holmes, LB (reprint author), Brigham & Womens Hosp, Dept Newborn Med, Teratol Unit, Act Malformat Surveillance Program, 75 Francis St, Boston, MA 02115 USA. EM Nina-Gold@hms.harvard.edu FU Massachusetts birth Defects Registry FX This study was supported by funds provided by the Massachusetts birth Defects Registry, which is part of the National Birth Defects Prevention Study, a Centers for Disease Control project. We thank the many pediatricians, geneticists, orthopedists, pathologists, and other specialists whose careful evaluations and thoughtful diagnoses contributed to the classification of the affected infants. We also thank Research Assistant Kathryn Rowan for her assistance with the classification of the affected infants born between 1994 and 2000. NR 36 TC 29 Z9 29 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUN PY 2011 VL 155A IS 6 BP 1225 EP 1235 DI 10.1002/ajmg.a.33999 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 781OV UT WOS:000291944200004 PM 21557466 ER PT J AU Hata, S Fujishige, S Araki, Y Taniguchi, M Urakami, K Peskind, E Akatsu, H Araseki, M Yamamoto, K Martins, RN Maeda, M Nishimura, M Levey, A Chung, KA Montine, T Leverenz, J Fagan, A Goate, A Bateman, R Holtzman, DM Yamamoto, T Nakaya, T Gandy, S Suzuki, T AF Hata, Saori Fujishige, Sayaka Araki, Yoichi Taniguchi, Miyako Urakami, Katsuya Peskind, Elaine Akatsu, Hiroyasu Araseki, Masahiko Yamamoto, Kazuo Martins, Ralph N. Maeda, Masahiro Nishimura, Masaki Levey, Allan Chung, Kathryn A. Montine, Thomas Leverenz, James Fagan, Anne Goate, Alison Bateman, Randall Holtzman, David M. Yamamoto, Tohru Nakaya, Tadashi Gandy, Sam Suzuki, Toshiharu TI Alternative Processing of gamma-Secretase Substrates in Common Forms of Mild Cognitive Impairment and Alzheimer's Disease: Evidence for gamma-Secretase Dysfunction SO ANNALS OF NEUROLOGY LA English DT Article ID BETA-PROTEIN PRECURSOR; IN-VIVO; METABOLISM; CLEAVAGE; MEMBRANE; ALCADEIN; ENZYME; BRAIN; RATIO AB Objective: The most common pathogenesis for familial Alzheimer's disease (FAD) involves misprocessing (or alternative processing) of the amyloid precursor protein (APP) by gamma-secretase due to mutations of the presenilin 1 (PS1) gene. This misprocessing/alternative processing leads to an increase in the ratio of the level of a minor gamma-secretase reaction product (A beta 42) to that of the major reaction product (A beta 40). Although no PS1 mutations are present, altered A beta 42/40 ratios are also observed in sporadic Alzheimer's disease (SAD), and these altered ratios apparently reflect deposition of A beta 42 as amyloid. Methods: Using immunoprecipitation-mass spectrometry with quantitative accuracy, we analyzed in the cerebrospinal fluid (CSF) of various clinical populations the peptide products generated by processing of not only APP but also an unrelated protein, alcadein (Alc). Alc undergoes metabolism by the identical APP alpha-secretases and gamma-secretases, yielding a fragment that we have named p3-Alca because of the parallel genesis of p3-Alc(alpha) peptides and the p3 fragment of APP. As with A beta, both major and minor p3-Alc(alpha)s are generated. We studied the alternative processing of p3-Alc(alpha) in various clinical populations. Results: We previously reported that changes in the A beta 42/40 ratio showed covariance in a linear relationship with the levels of p3-Alc(alpha) [minor/major] ratio in media conditioned by cells expressing FAD-linked PS1 mutants. Here we studied the speciation of p3-Alc(alpha) in the CSF from 3 groups of human subjects (n 158): elderly nondemented control subjects; mild cognitive impairment (MCI) subjects with a clinical dementia rating (CDR) of 0.5; SAD subjects with CDR of 1.0; and other neurological disease (OND) control subjects. The CSF minor p3-Alc(alpha) variant, p3-Alc(alpha)38, was elevated (p < 0.05) in MCI subjects or SAD subjects, depending upon whether the data were pooled and analyzed as a single cohort or analyzed individually as 3 separate cohorts. Interpretation: These results suggest that some SAD may involve alternative processing of multiple c-secretase substrates, raising the possibility that the molecular pathogenesis of SAD might involve gamma-secretase dysfunction. ANN NEUROL 2011;69:1026-1031 C1 [Suzuki, Toshiharu] Hokkaido Univ, Neurosci Lab, Grad Sch Pharmaceut Sci, Dept Neurosci,Kita Ku, Sapporo, Hokkaido 0600812, Japan. [Taniguchi, Miyako; Urakami, Katsuya] Tottori Univ, Fac Med, Sch Hlth Sci, Dept Regulat Biol, Yonago, Tottori 683, Japan. [Peskind, Elaine] Univ Washington, Med Ctr, Dept Psychiat, Seattle, WA 98195 USA. [Peskind, Elaine] Univ Washington, Med Ctr, Alzheimers Dis Res Ctr, Seattle, WA 98195 USA. [Peskind, Elaine] VA Puget Sound Hlth Care Ctr, Seattle, WA USA. [Akatsu, Hiroyasu] Fukushimura Hosp, Choju Med Inst, Toyohashi, Aichi, Japan. [Yamamoto, Kazuo] Univ Tokyo, Dept Integrated Biosci, Grad Sch Frontier Sci, Kashiwa, Chiba, Japan. [Martins, Ralph N.] Edith Cowan Univ, Ctr Excellence Alzheimers Dis Res & Care, Joondalup, WA, Australia. [Martins, Ralph N.] Edith Cowan Univ, Sir James McCusker Alzheimers Dis Res Unit, Sch Exercise Biomed & Hlth Sci, Joondalup, WA, Australia. [Maeda, Masahiro] Immunobiol Labs Co Ltd IBL, Fujioka, Japan. [Nishimura, Masaki] Shiga Univ Med Sci, Neurol Unit, Mol Neurosci Res Ctr, Otsu, Shiga 52021, Japan. [Levey, Allan] Emory Univ, Dept Neurol, Emory Alzheimers Dis Res Ctr, Atlanta, GA 30322 USA. [Chung, Kathryn A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Montine, Thomas] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Fagan, Anne; Bateman, Randall; Holtzman, David M.] Washington Univ, Sch Med, Dept Neurol, Alzheimers Diseaase Reasrearch Ctr, St Louis, MO 63110 USA. [Gandy, Sam] Mt Sinai Sch Med, Dept Neurol, Alzheimers Dis Res Ctr, New York, NY USA. [Gandy, Sam] James J Peters Vet Adm Med Ctr, Bronx, NY USA. RP Suzuki, T (reprint author), Hokkaido Univ, Neurosci Lab, Grad Sch Pharmaceut Sci, Dept Neurosci,Kita Ku, Kita12,Nishi6, Sapporo, Hokkaido 0600812, Japan. EM tsuzuki@pharm.hokudai.ac.jp RI Hata, Saori /A-3829-2012; Yamamoto, Tohru/A-3801-2012; Suzuki, Toshiharu/B-5342-2013 OI Yamamoto, Tohru/0000-0002-1652-0233; FU Ministry of Education, Science, Culture, Sports, and Technology, Japan [20023001]; Washington University Alzheimer's Disease Research Center [P50 AG05681, P01AG03991]; University of Washington P50 Alzheimer's Disease Research Center; US Department of Veterans Affairs; Kurozumi Medical Foundation; Suzuken Memorial Foundation; National Institute on Aging [P01 AG10491, P50 AG005138]; Japan Society for the Promotion of Science (JSPS) FX This research was supported by a grant from the Ministry of Education, Science, Culture, Sports, and Technology, Japan (Grants-in-Aid for Scientific Research on Priority Areas 20023001 to T. S.).; We thank Patrick Hof, Brandon Wustman, Rosalie Crouch, and Yuhki Saito for helpful discussions. Some CSF samples from aged nondemented control subjects and from subjects suffering from various neurological diseases were provided by the Washington University Biomarkers Core, which is supported by the Washington University Alzheimer's Disease Research Center grant P50 AG05681 and P01AG03991. Some CSF samples were provided by the Washington University Resource Bank, which is supported by P50 AG05681 and P01 AG03991, and the University of Washington Resource Bank, which is supported by the University of Washington P50 Alzheimer's Disease Research Center and the US Department of Veterans Affairs. Some samples were also contributed by the Tottori University School of Health Sciences.; T. S. and T.N. are supported by Kurozumi Medical Foundation and Suzuken Memorial Foundation. S. G. is supported by National Institute on Aging grants P01 AG10491 and P50 AG005138. Authors S. H., Y.A., and M. A. are the recipients of research fellowships from the Japan Society for the Promotion of Science (JSPS) for young scientists. The other authors report no conflicts of interest. NR 17 TC 20 Z9 21 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2011 VL 69 IS 6 BP 1026 EP 1031 DI 10.1002/ana.22343 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 782JA UT WOS:000292003100015 PM 21681798 ER PT J AU Becker, JA Hedden, T Carmasin, J Maye, J Rentz, DM Putcha, D Fischl, B Greve, DN Marshall, GA Salloway, S Marks, D Buckner, RL Sperling, RA Johnson, KA AF Becker, J. Alex Hedden, Trey Carmasin, Jeremy Maye, Jacqueline Rentz, Dorene M. Putcha, Deepti Fischl, Bruce Greve, Douglas N. Marshall, Gad A. Salloway, Stephen Marks, Donald Buckner, Randy L. Sperling, Reisa A. Johnson, Keith A. TI Amyloid-beta Associated Cortical Thinning in Clinically Normal Elderly SO ANNALS OF NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; PITTSBURGH COMPOUND-B; PRECLINICAL ALZHEIMERS-DISEASE; HUMAN CEREBRAL-CORTEX; NORMAL OLDER-ADULTS; FUNCTIONAL CONNECTIVITY; STRUCTURAL MRI; TEMPORAL-LOBE; AD DEMENTIA; VOLUME LOSS AB Objective: Both amyloid-beta (A beta) deposition and brain atrophy are associated with Alzheimer's disease (AD) and the disease process likely begins many years before symptoms appear. We sought to determine whether clinically normal (CN) older individuals with A beta deposition revealed by positron emission tomography (PET) imaging using Pittsburgh Compound B (PiB) also have evidence of both cortical thickness and hippocampal volume reductions in a pattern similar to that seen in AD. Methods: A total of 119 older individuals (87 CN subjects and 32 patients with mild AD) underwent PiB PET and high-resolution structural magnetic resonance imaging (MRI). Regression models were used to relate PiB retention to cortical thickness and hippocampal volume. Results: We found that PiB retention in CN subjects was (1) age-related and (2) associated with cortical thickness reductions, particularly in parietal and posterior cingulate regions extending into the precuneus, in a pattern similar to that observed in mild AD. Hippocampal volume reduction was variably related to Ab deposition. Interpretation: We conclude that Ab deposition is associated with a pattern of cortical thickness reduction consistent with AD prior to the development of cognitive impairment. ANN NEUROL 2011;69:1032-1042 C1 [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol,Med Sch, Boston, MA 02114 USA. [Rentz, Dorene M.; Marshall, Gad A.; Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Buckner, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Hedden, Trey; Putcha, Deepti; Fischl, Bruce; Greve, Douglas N.; Buckner, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Rentz, Dorene M.; Marshall, Gad A.; Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02114 USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Salloway, Stephen] Brown Univ, Dept Neurol, Warren Alpert Med Sch, Providence, RI 02912 USA. [Salloway, Stephen] Butler Hosp, Memory & Aging Program, Providence, RI 02906 USA. [Marks, Donald] Tufts Sch Med, Boston, MA USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.] Howard Hughes Med Inst, Cambridge, MA USA. RP Johnson, KA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol,Med Sch, Bartlett 507,33 Fruit St, Boston, MA 02114 USA. EM kajohnson@partners.org OI Kennedy, Kristen/0000-0001-5373-9026 FU National Institutes of Health (NIH) (National Institute on Aging [NIA] [R01-AG027435-S1, P50-AG00513421, P01-AG036694, R01-AG021910, 1K23AG033634]; Massachusetts Alzheimer's Disease Research Center (ADRC); Howard Hughes Medical Institute (HHMI); Alzheimer Association [IIRG-06-32444, IIRG-08-90934]; Charles H. Farnsworth Trust, Boston, MA; The Rosalinde and Arthur Gilbert Foundation; NIH; Elan Pharmaceuticals; Wyeth; Bristol-Myers Squibb; Janssen Immunotherapy; Pfizer Inc.; Bayer; Eisai Inc.; Myriad Genetics, Inc.; GlaxoSmithKline; Neurochem-Alzhemed; Cephalon, Inc.; Forest Laboratories Inc.; Alzheimer's Disease Neuroimaging Initiative; Dominantly Inherited Alzheimer's Network [NIA 1U01AG032438-01]; Aging Brain: DTI, Subcortical Ischemia and Behavior [NIA 1 R03 AG023916-01A1]; The Norman and Rosalie Fain Family Foundation; Champlin Foundation; John and Happy White Family Foundation; NIH/National Institute on Aging; The Alzheimer Association FX This research was supported by grants from the National Institutes of Health (NIH) (National Institute on Aging [NIA] R01-AG027435-S1 to R. A. S. and K.A.J.; P50-AG00513421 to K.A.J. and R. A. S.; P01-AG036694 to R. A. S., K.A.J, and R. L. B; R01-AG021910 to R. L. B.) 1K23AG033634 to G. A. M.; Massachusetts Alzheimer's Disease Research Center (ADRC); Howard Hughes Medical Institute (HHMI) (to R. L. B.); Alzheimer Association (IIRG-06-32444 to R. A. S. and K.A.J.; IIRG-08-90934 to D. M. R. and K.A.J.); Charles H. Farnsworth Trust, Boston, MA (to D. M. R.); The Rosalinde and Arthur Gilbert Foundation/AFAR New Investigation Awards in Alzheimer's Disease (to G.A.M.) and an anonymous medical foundation.; J.C., T. H., D. P., J.A.B., J.M., . M. R., G. A. M. and R. L. B. have none to report. B. F. has received one or more grants and has a grant pending from the NIH. D. M. is involved with an ongoing phase 3 clinical trial with Elan Pharmaceuticals and Janssen Immunotherapy, and is on the speakers' bureaus of Novartis and Pfizer. S. S. serves on the scientific advisory boards of Elan Pharmaceuticals, Sanofi-Aventis, Pfizer Inc., Eisai Inc., and Bristol-Myers Squibb; serves as Associate Editor for the Journal of Neuropsychiatry and Clinical Neurosciences; receives publishing royalties for The Frontal Lobes and Neuropsychiatric Illness (American Psychiatric Press, Inc., 2001), The Neuropsychiatry of Limbic and Subcortical Disorders (American Psychiatric Press, Inc., 1997), and Vascular Dementia (Humana Press, 2004); receives honoraria from Eisai Inc., Pfizer Inc, Novartis, Forest Laboratories Inc., Elan Pharmaceuticals, and Athena Diagnostics, Inc.; holds corporate appointments with Merck Serono and Medivation, Inc.; receives research support from Elan Pharmaceuticals, Wyeth, Bristol-Myers Squibb, Janssen Immunotherapy, Pfizer Inc., Bayer, and Eisai Inc.; received research support from Myriad Genetics, Inc., GlaxoSmithKline, Neurochem-Alzhemed, Cephalon, Inc., and Forest Laboratories Inc.; receives research support from the Alzheimer's Disease Neuroimaging Initiative, Dominantly Inherited Alzheimer's Network (NIA 1U01AG032438-01); received research support from Aging Brain: DTI, Subcortical Ischemia and Behavior (NIA 1 R03 AG023916-01A1); and receives research support from The Norman and Rosalie Fain Family Foundation, the Champlin Foundation, and the John and Happy White Family Foundation. D. G. has a grant from the NIH. K. A. J. has received grants and has grants pending from the NIH/National Institute on Aging and The Alzheimer Association. R. A. S. has a grant pending from the NIH/National Institute on Aging. NR 76 TC 137 Z9 138 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2011 VL 69 IS 6 BP 1032 EP 1042 DI 10.1002/ana.22333 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 782JA UT WOS:000292003100016 PM 21437929 ER PT J AU Rajewsky, K AF Rajewsky, K. TI RAPPAPORT LECTURE: MODELING HUMAN LYMPHOMAGENESIS IN MICE SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [Rajewsky, K.] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Rajewsky, K.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 80 EP 80 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300019 ER PT J AU Smith, MR Li, H Gordon, L Gascoyne, R Paietta, E Forero-Torres, A Kahl, B Advani, R Hong, F Horning, S AF Smith, M. R. Li, H. Gordon, L. Gascoyne, R. Paietta, E. Forero-Torres, A. Kahl, B. Advani, R. Hong, F. Horning, S. TI PHASE II STUDY OF R-CHOP FOLLOWED BY Y-90-IBRITUMOMAB TIUXETAN IN UNTREATED MANTLE CELL LYMPHOMA (MCL): 5 YEAR FOLLOW-UP OF EASTERN COOPERATIVE ONCOLOGY GROUP E1499 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [Smith, M. R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Li, H.; Hong, F.] Dana Farber Canc Inst, Ctr Stat, Boston, MA 02115 USA. [Gordon, L.] Northwestern Univ, Chicago, IL 60611 USA. [Gascoyne, R.] Brit Columbia Canc Agcy, Vancouver, BC, Canada. [Paietta, E.] Montefiore Med Ctr, New York, NY USA. [Forero-Torres, A.] Univ Alabama, Birmingham, AL USA. [Kahl, B.] Univ Wisconsin, Madison, WI 53706 USA. [Advani, R.] Stanford Univ, Stanford, CA 94305 USA. [Horning, S.] Genentech Inc, San Francisco, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 86 EP 87 PG 2 WC Oncology SC Oncology GA 782GK UT WOS:000291996300034 ER PT J AU Chapuy, B Green, M Lu, J Monti, S Hao, Y Yeda, K Rodig, S Curie, T Takeyama, K Golub, T Kutok, J Shipp, M AF Chapuy, B. Green, M. Lu, J. Monti, S. Hao, Y. Yeda, K. Rodig, S. Curie, T. Takeyama, K. Golub, T. Kutok, J. Shipp, M. TI IDENTIFICATION OF A "DELETION BLOCK'' AT 13Q14 THAT PERTURBS MULTIPLE SIGNALING AND SURVIVAL PATHWAYS IN PRIMARY CLASSICAL HODGKIN LYMPHOMA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [Chapuy, B.; Green, M.; Hao, Y.; Yeda, K.; Takeyama, K.; Shipp, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lu, J.; Monti, S.; Golub, T.] Broad Inst, Canc Program, Cambridge, MA USA. [Rodig, S.; Curie, T.; Kutok, J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 101 EP 101 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300076 ER PT J AU Gordon, L Weller, E Armand, P Devine, S Holland, H Mason, J Winter, J Kaminski, M Nagler, A AF Gordon, L. Weller, E. Armand, P. Devine, S. Holland, H. Mason, J. Winter, J. Kaminski, M. Nagler, A. TI A PHASE II STUDY OF CT-011, AN ANTI-PD-1 ANTIBODY, AFTER AUSCT IN RECURRENT/REFRACTORY DLBCL: FIRST ANALYSIS OF PROGRESSION-FREE-SURVIVAL (PFS), OVERALL SURVIVAL (OS) AND TOXICITY (TOX) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [Gordon, L.; Winter, J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Weller, E.; Armand, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Devine, S.] Ohio State Univ, Columbus, OH 43210 USA. [Holland, H.] Northside Hosp, Atlanta, GA USA. [Mason, J.] Scripps Clin, San Diego, CA USA. [Kaminski, M.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nagler, A.] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 102 EP 102 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300080 ER PT J AU Freedman, A Kuruvilla, J Assouline, S Engert, A Heo, D Solal-Celigny, P Corradini, P Verhoef, G Younes, A Bendiske, J Ewald, B Dey, J Baeck, J Bilic, S Rediske, J Fanale, M AF Freedman, A. Kuruvilla, J. Assouline, S. Engert, A. Heo, D. Solal-Celigny, P. Corradini, P. Verhoef, G. Younes, A. Bendiske, J. Ewald, B. Dey, J. Baeck, J. Bilic, S. Rediske, J. Fanale, M. TI ANTI-CD40 MONOCLONAL ANTIBODY LUCATUMUMAB EXHIBITS ANTI-TUMOR ACTIVITY IN FOLLICULAR LYMPHOMA AND OTHER LYMPHOMA SUBTYPES: PHASE I/II PRELIMINARY FINDINGS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 [Freedman, A.] DFCI, Oncol, Boston, MA USA. [Kuruvilla, J.] Univ Toronto, Toronto, ON, Canada. [Assouline, S.] McGill Univ, Montreal, PQ, Canada. [Engert, A.] Univ Cologne, Cologne, Germany. [Heo, D.] Seoul Natl Univ Hosp, Seoul, South Korea. [Solal-Celigny, P.] Serv Hematol, Le Mans, France. [Corradini, P.] Univ Milan, Milan, Italy. [Verhoef, G.] Univ Hosp Gasthuisberg, Louvain, Belgium. [Younes, A.; Fanale, M.] MDACC, Houston, TX USA. [Bendiske, J.; Ewald, B.; Dey, J.; Baeck, J.; Bilic, S.; Rediske, J.] Novartis, Oncol, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 104 EP 104 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300521 ER PT J AU De Jong, D Wahlin, B Sander, B Xie, W Salles, G Weller, E AF De Jong, D. Wahlin, B. Sander, B. Xie, W. Salles, G. Weller, E. TI THE RELIABILITY OF IMMUNOHISTOCHEMICAL ANALYSIS OF TUMOR MICROENVIRONMENT IN FOLLICULAR LYMPHOMA; A VALIDATION STUDY FROM THE LUNENBURG LYMPHOMA BIOMARKER CONSORTIUM (LLBC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [De Jong, D.] Netherlands Canc Inst, Amsterdam, Netherlands. [Wahlin, B.; Sander, B.] Karolinska Inst, Stockholm, Sweden. [Xie, W.; Weller, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Salles, G.] Univ Lyon 1, F-69365 Lyon, France. NR 0 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 108 EP 108 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300089 ER PT J AU Roccaro, AM Sacco, A Azab, A Maiso, P Liu, Y Zhang, Y Azab, F Ngo, HT Ghobrial, IM AF Roccaro, A. M. Sacco, A. Azab, A. Maiso, P. Liu, Y. Zhang, Y. Azab, F. Ngo, H. T. Ghobrial, I. M. TI MICRORNA-9*REG