FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kraitchman, DL Caravan, P AF Kraitchman, Dara L. Caravan, Peter TI Magnetic Resonance Labeling of Stem Cells Is Positive Tracking a Plus or a Minus? SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE cardiac magnetic resonance; gadolinium; atherosclerotic plaque; stem cells ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR FUNCTION; GADOFLUORINE-M; CONTRAST AGENT; NEURAL TRANSPLANTS; METAANALYSIS; IRON; TRIALS C1 [Kraitchman, Dara L.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Caravan, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging, Boston, MA USA. RP Kraitchman, DL (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 600 N Wolfe St,314 Pk Bldg, Baltimore, MD 21287 USA. EM dara@mri.jhu.edu FU NHLBI NIH HHS [R33 HL089029, R33 HL089029-03] NR 18 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD SEP PY 2009 VL 2 IS 9 BP 1123 EP 1125 DI 10.1016/j.jcmg.2009.05.010 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 725OL UT WOS:000287654900014 PM 19761993 ER PT J AU Lichtenwalter, C de Lemos, JA Roesle, M Obel, O Holper, EM Haagen, D Saeed, B Iturbe, JM Shunk, K Bissett, JK Sachdeva, R Voudris, VV Karyofillis, P Kar, B Rossen, J Fasseas, P Berger, P Banerjee, S Brilakis, ES AF Lichtenwalter, Christopher de Lemos, James A. Roesle, Michele Obel, Owen Holper, Elizabeth M. Haagen, Donald Saeed, Bilal Iturbe, Jose Miguel Shunk, Kendrick Bissett, Joseph K. Sachdeva, Rajesh Voudris, Vassilios V. Karyofillis, Panagiotis Kar, Biswajit Rossen, James Fasseas, Panayotis Berger, Peter Banerjee, Subhash Brilakis, Emmanouil S. TI Clinical Presentation and Angiographic Characteristics of Saphenous Vein Graft Failure After Stenting Insights From the SOS (Stenting Of Saphenous Vein Grafts) Trial SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE bare-metal stents; coronary artery bypass graft surgery; drug-eluting stents; outcomes; percutaneous coronary intervention; saphenous vein grafts ID BARE-METAL STENT; PACLITAXEL-ELUTING STENT; CORONARY-ARTERY-DISEASE; FOLLOW-UP; BALLOON ANGIOPLASTY; BYPASS GRAFTS; LESIONS; IMPLANTATION; RESTENOSIS; EVENTS AB Objectives We sought to compare the clinical presentation and angiographic patterns of saphenous vein graft (SVG) failure after stenting with a paclitaxel-eluting stent (PES) versus a similar bare-metal stent (BMS). Background The mode of SVG failure after stenting has been poorly characterized. Methods The SOS (Stenting Of Saphenous Vein Grafts) trial enrolled 80 patients with 112 lesions in 88 SVGs who were randomized to a BMS or PES. Angiographic follow-up at 12 months was available in 83% of the patients. Results Binary angiographic restenosis occurred in 51% (24 of 47) of BMS-treated lesions versus 9% (4 of 43) of PES-treated lesions (p < 0.0001). Graft occlusion occurred in 9 of the 21 SVGs (43%) that failed in the BMS group and in 2 of 4 SVGs (50%) that failed in the PES group. SVG failure after stenting presented as an acute coronary syndrome in 10 of the 24 patients (42%) (7 of those 10 patients presented with non-ST-segment elevation acute myocardial infarction), stable angina in 9 (37%) patients, and without symptoms in 5 (21%) patients. Of the 19 patients (with 20 grafts) who developed symptomatic graft failure, repeat SVG revascularization was successfully performed in all 13 (100%) subtotally obstructed SVGs but was attempted (and successful) in only 1 of 7 (14%) occluded SVGs. Revascularization of a native coronary artery was performed in an additional 4 of 7 (57%) symptomatic patients with an occluded SVG. Conclusions SVG failure after stenting often presents as acute myocardial infarction and with SVG occlusion. Compared with BMS, PES reduce SVG failure. (J Am Coll Cardiol Intv 2009;2:855-60) (C) 2009 by the American College of Cardiology Foundation C1 [Lichtenwalter, Christopher; de Lemos, James A.; Roesle, Michele; Obel, Owen; Haagen, Donald; Iturbe, Jose Miguel; Banerjee, Subhash; Brilakis, Emmanouil S.] Vet Affairs N Texas Healthcare Syst, Dallas, TX USA. [Lichtenwalter, Christopher; de Lemos, James A.; Obel, Owen; Holper, Elizabeth M.; Iturbe, Jose Miguel; Banerjee, Subhash; Brilakis, Emmanouil S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Saeed, Bilal] Univ Toledo, Dept Internal Med, Toledo, OH 43606 USA. [Shunk, Kendrick] Univ Calif San Francisco, Sch Med, San Francisco VA Med Ctr, San Francisco, CA USA. [Bissett, Joseph K.; Sachdeva, Rajesh] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Bissett, Joseph K.; Sachdeva, Rajesh] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Voudris, Vassilios V.; Karyofillis, Panagiotis] Onassis Cardiac Surg Ctr, Athens, Greece. [Kar, Biswajit] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rossen, James] Iowa City Vet Affairs Med Ctr, Iowa City, IA USA. [Fasseas, Panayotis] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Berger, Peter] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA. RP Brilakis, ES (reprint author), Dallas VA Med Ctr 111A, 4500 S Lancaster Rd, Dallas, TX 75216 USA. EM esbrilakis@yahoo.com RI Brilakis, Emmanouil/B-5282-2009; OI Sachdeva, Rajesh/0000-0002-7729-6247; Brilakis, Emmanouil/0000-0001-9416-9701 FU Veteran Affairs [VISN-17]; Harris Methodist Foundation; Bristol-Myers Squibb/Sanofi-Aventis; Boston Scientific FX The study was presented at the SCAI's 2009 Annual Scientific Sessions in Las Vegas, Nevada. The SOS trial was funded by a Veteran Affairs VISN-17 Startup Award and by a Clark R. Gregg Grant of the Harris Methodist Foundation to Dr. Brilakis. Dr. de Lemos has received speaker honoraria from Bristol-Myers Squibb/Sanofi-Aventis and consulting income from Johnson and Johnson (<$10,000). Dr. Obel works predominantly with cardiac rhythm devices and has speaker agreements with St. Jude, Medtronic, and Boston Scientific. Dr. Rossen participated in multicenter clinical studies supported by Boston Scientific. Dr. Berger has served as a consultant to PlaCor, Eli Lilly, Accumetrics, The Medicines Company, and Eli Lilly/Daiichi-Sankyo (each for <$10,000) and owns equity in Lumen, Inc. NR 23 TC 27 Z9 27 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD SEP PY 2009 VL 2 IS 9 BP 855 EP 860 DI 10.1016/j.jcin.2009.06.014 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 613IC UT WOS:000278971600007 PM 19778774 ER PT J AU George, JC Popma, JJ AF George, Jon C. Popma, Jeffrey J. TI Reduced Reimbursement for Cardiovascular Services by the Centers for Medicare and Medicaid Services Perspective From Interventional Cardiology SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article ID HEALTH-CARE; REFORM AB The Centers for Medicare and Medicaid Services (CMS) recently released its proposed 2010 Medicare Physician Fee Schedule, which includes dramatic reductions in payments for cardiovascular services. However, the basis for these cuts is flawed in credibility and does not address the valid issues that demand health care reform. (J Am Coll Cardiol Intv 2009;2:894-6) (C) 2009 by the American College of Cardiology Foundation C1 [George, Jon C.] Temple Univ Hosp & Med Sch, Div Cardiovasc Med, Philadelphia, PA 19140 USA. [Popma, Jeffrey J.] Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02215 USA. RP George, JC (reprint author), Temple Univ Hosp & Med Sch, Div Cardiovasc Med, 9th Floor Parkinson Pavil, Philadelphia, PA 19140 USA. EM jcgeorgemd@hotmail.com NR 11 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD SEP PY 2009 VL 2 IS 9 BP 894 EP 896 DI 10.1016/j.jcin.2009.08.002 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 613IC UT WOS:000278971600014 PM 19778781 ER PT J AU Reisner, SL Mimiaga, MJ Bland, S Mayer, KH Perkovich, B Safren, SA AF Reisner, Sari L. Mimiaga, Matthew J. Bland, Sean Mayer, Kenneth H. Perkovich, Brandon Safren, Steven A. TI HIV Risk and Social Networks Among Male-to-Female Transgender Sex Workers in Boston, Massachusetts SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE HIV; intervention development; sexually transmitted diseases; transgender; trans mothers ID HUMAN-IMMUNODEFICIENCY-VIRUS; BASE-LINE DATA; CAGE QUESTIONNAIRE; SAN-FRANCISCO; NEEDS-ASSESSMENT; UNITED-STATES; HEALTH-CARE; BEHAVIORS; MEN; PREVENTION AB Male-to-male transgender individuals who fie engage in sex work constitute a group at high risk for HIV infection in the United States. This mixed-methods formative study examined sexual risk among preoperative transgender male-to-female sex workers (N = 11) in Boston. More than one third of the participants were HIV-infected and reported a history of sexually transmitted diseases. Participants had a mean of 36 (SD = 72) transactional male sex partners in the past 12 months, and a majority reported at least one episode of unprotected anal sex. Qualitative themes included (a) sexual risk, (b) motivations for engaging in sex work, (c) consequences of sex work, (d) social networks (i.e., "trans mothers," who played a pivotal role in initiation into sex work), and (e) potential intervention strategies. Results suggest that interventions with transgender male-to-female sex workers must be at multiple levels and address the psychosocial and environmental contexts in which sexual risk behavior occurs. C1 [Reisner, Sari L.; Mimiaga, Matthew J.; Bland, Sean; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mayer, Kenneth H.] Brown Univ, AIDS Program, Providence, RI 02912 USA. [Mayer, Kenneth H.] Brown Univ, Sch Med, Providence, RI 02912 USA. [Perkovich, Brandon] Harvard Univ, Cambridge, MA USA. [Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Reisner, SL (reprint author), Fenway Hlth, Fenway Inst, Boston, MA USA. FU The Fenway Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [R21HD051178]; National Institute on Drug Abuse (NIDA) [R03DA023393]; National Institutes of Health [P30 A142853] FX The project described in this article was supported by The Center for Population Research in Lesbian, Gay, Bisexual, and Transgender Health at The Fenway Institute and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) under Award Number R21HD051178. Some of the investigator time on this project was also supported by grant number R03DA023393 from the National Institute on Drug Abuse (NIDA) and from the Lifespan/Tufts/Brown University Center for AIDS Research grant P30 A142853 from the National Institutes of Health. Content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD, NIDA, or the NIH. NR 44 TC 25 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-3290 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD SEP-OCT PY 2009 VL 20 IS 5 BP 373 EP 386 DI 10.1016/j.jana.2009.06.003 PG 14 WC Nursing SC Nursing GA 498DM UT WOS:000270117000006 PM 19732696 ER PT J AU Adams, JC AF Adams, Joe C. TI Immunocytochemical Traits of Type IV Fibrocytes and Their Possible Relations to Cochlear Function and Pathology SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE spiral ligament; hearing loss; cochlea; acoustic trauma ID TISSUE GROWTH-FACTOR; INDUCED HEARING-LOSS; INNER-EAR; SPIRAL LIGAMENT; MOUSE COCHLEA; GAP-JUNCTIONS; RAT COCHLEA; PROTEIN LRP; NOISE; RECEPTOR AB One of the more consistent and least understood changes in the aging human cochlea is the progressive loss of fibrocytes within the spiral ligament. This report presents an animal model for type IV fibrocyte loss, along with immunocytochemical evidence that noise-induced loss of these cells may account for previously unexplained hearing losses. The remarkably low threshold for noise-induced loss of type IV fibrocytes, approximately 24 dB less than the threshold for adjacent hair cell destruction, may account for the prevalence of missing fibrocytes in humans. In mice, changes in the spectrum of traumatizing noise had little effect upon the site of loss of the fibrocytes, suggesting that the primary site of damage that induced the loss was the basal-most cochlear turn, a site expected to be damaged by all three noise bands. Type IV fibrocytes were found to immunostain for connective tissue growth factor (CTGF) and for transforming growth factor beta receptor 3, a receptor that is known to activate CTGF expression. Type IV fibrocytes lack immunostaining for adenosine triphosphatase and connexins that are key players in potassium ion uptake and transmission, which suggests that they play little, if any, role in potassium recycling from perilymphatic space to the endolymphatic space. Consequently, their loss probably does not directly reduce this process. Immunostaining for a receptor for CTGF, low-density-lipoprotein-related protein 1, indicated that CTGF acts as an autocrine and a paracrine agent within the cochlea. The lack of CTGF paracrine effects following noise-induced loss of type IV fibrocytes may account for previously unexplained hearing losses. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Adams, JC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Joe_Adams@meei.harvard.edu FU NIH [DC003929] FX This work was funded by NIH grant DC003929. Funding of the Affymetrix chip project was through the generosity of Mr. and Mrs. Charles Safford. The author is indebted to the unpublished findings of Dr. Michiko Node for prompting an interest in type IV fibrocytes. Technical help was provided by Sarah McCaffrey. Thanks go to Sarah McCaffrey, Jennifer O'Malley, Saumil Merchant, and Charles Liberman for comments and suggestions on the manuscript. The NKCC1 antibody developed by Dr. Lytle was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA 52242, USA. NR 50 TC 16 Z9 16 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD SEP PY 2009 VL 10 IS 3 BP 369 EP 382 DI 10.1007/s10162-009-0165-z PG 14 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 477CQ UT WOS:000268495600005 PM 19277783 ER PT J AU Lilaonitkul, W Guinan, JJ AF Lilaonitkul, Watjana Guinan, John J., Jr. TI Human Medial Olivocochlear Reflex: Effects as Functions of Contralateral, Ipsilateral, and Bilateral Elicitor Bandwidths SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE cochlear amplifier; feedback; masking; antimasking; spatial summation ID OUTER HAIR-CELLS; FREQUENCY OTOACOUSTIC EMISSIONS; SUPERIOR OLIVARY COMPLEX; AUDITORY-NERVE RESPONSE; ELECTRICAL-STIMULATION; BASILAR-MEMBRANE; GUINEA-PIG; RECIPROCAL SYNAPSES; EFFERENT NEURONS; SPIRAL GANGLION AB Animal studies have led to the view that the acoustic medial olivocochlear (MOC) efferent reflex provides sharply tuned frequency-specific feedback that inhibits cochlear amplification. To determine if MOC activation is indeed narrow band, we measured the MOC effects in humans elicited by 60-dB sound pressure level (SPL) contralateral, ipsilateral, and bilateral noise bands as a function of noise bandwidth from 1/2 to 6.7 octaves. MOC effects were quantified by the change in stimulus frequency otoacoustic emissions from 40 dB SPL probe tones near 0.5, 1, and 4 kHz. In a second experiment, the noise bands were centered 2 octaves below probe frequencies near 1 and 4 kHz. In all cases, the MOC effects increased as elicitor bandwidth increased, with the effect saturating at about 4 octaves. Generally, the MOC effects increased as the probe frequency decreased, opposite expectations based on MOC innervation density in the cochlea. Bilateral-elicitor effects were always the largest. The ratio of ipsilateral/contralateral effects depended on elicitor bandwidth; the ratio was large for narrow-band probe-centered elicitors and approximately unity for wide-band elicitors. In another experiment, the MOC effects from increasing elicitor bandwidths were calculated from measurements of the MOC effects from adjacent half-octave noise bands. The predicted bandwidth function agreed well with the measured bandwidth function for contralateral elicitors, but overestimated it for ipsilateral and bilateral elicitors. Overall, the results indicate that (1) the MOC reflexes integrate excitation from almost the entire cochlear length, (2) as elicitor bandwidth is increased, the excitation from newly stimulated cochlear regions more than overcomes the reduced excitation at frequencies in the center of the elicitor band, and (3) contralateral, ipsilateral, and bilateral elicitors show MOC reflex spatial summation over most of the cochlea, but ipsilateral spatial summation is less additive than contralateral. C1 [Lilaonitkul, Watjana] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Lilaonitkul, Watjana; Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Guinan, John J., Jr.] Harvard Mit Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM John_Guinan@meei.harvard.edu FU National Institute of Deafness and Other Communication Disorders [RO1 DC-005977, P30 DC-05029] FX We thank Dr. L. D. Braida, Dr. M. C. Brown, Dr. Oded Ghitza, Dr. M. C. Liberman, Dr. S. F. Maison, Dr. W. T. Peake, and Dr. C. A. Shera for comments on the manuscript. This work was supported by National Institute of Deafness and Other Communication Disorders Grants RO1 DC-005977 and P30 DC-05029. NR 52 TC 43 Z9 43 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD SEP PY 2009 VL 10 IS 3 BP 459 EP 470 DI 10.1007/s10162-009-0163-1 PG 12 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 477CQ UT WOS:000268495600011 PM 19263165 ER PT J AU Utikal, J AF Utikal, J. TI Reprogramming of melanocytic cells into induced pluripotent stem cells SO JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT LA English DT Meeting Abstract C1 [Utikal, J.] Ruprecht Karl Univ Heidelberg, Dept Dermatol Venereol & Allergol, Univ Med Ctr Mannheim, Mannheim, Germany. [Utikal, J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Utikal, J.] Harvard Stem Cell Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1610-0379 J9 J DTSCH DERMATOL GES JI J. Dtsch. Dermatol. Ges. PD SEP PY 2009 VL 7 IS 9 BP 841 EP 842 PG 2 WC Dermatology SC Dermatology GA 488SZ UT WOS:000269371500070 ER PT J AU Glezer, A Byatt, N Cook, R Rothschild, AJ AF Glezer, Anna Byatt, Nancy Cook, Richard, Jr. Rothschild, Anthony J. TI Polypharmacy prevalence rates in the treatment of unipolar depression in an outpatient clinic SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Psychopharmacology; Polypharmacy; Depression; Treatment ID SEROTONIN REUPTAKE INHIBITORS; ANTIDEPRESSANT; COST AB Objective: Unipolar depression is a complex illness with an ever increasing number of pharmacological treatments available. As the number of available medication options increases, so does the potential for polypharmacy, a practice with possible complications. Such complications include a greater number of side effects with the initiation of additional medications and the consequences of drug-drug interactions. Therefore, it is important to understand the effects of polypharmacy on efficacy of treatment as well as whether polypharmacy is instituted after appropriate initial monotherapy trials. This study attempts to answer these questions. Methods: Patient names for this investigation were provided by residents in the UMass Medical School Psychiatry Residency program. The charts of these patients were analyzed to collect data regarding demographics, clinical data about the illness, medication names, types, duration of use and to access efficacy using the Clinical Global Impression (CGI). Results: Of 160 reviewed charts, 135 subjects were included in the final analyses (others excluded due to incomplete data or no depression diagnosis). Patients were on average on 2.0 medications (So = 0.5) with 2.1 past trials. A greater number of current antidepressant medications did not correlate with a greater improvement in CGI, implying that polypharmacy did not necessarily lead to greater efficacy. The impact of illness severity, as measured by comorbidities, substance abuse, and trauma history, were included in the analysis, and did not significantly change this outcome. Additionally, prescription patterns themselves were examined, including reasons for termination of medication trials, the impact of side-effects, and the number of patients that had complete monotherapy trials before transitioning to polypharmacy. Study limitations: Small sample size, retrospective review, one CGI rater. Conclusions: First, many patients did not receive an adequate monotherapy trial, as defined by dose and duration, before progressing to polypharmacy. Secondly, the use of two or more medications concurrently did not appear to increase efficacy as measured by CGI. Due to study limitations. direct comparison of the efficacy of one and two medications was not significant; however the study did demonstrate a general correlation between polypharmacy and greater depressive symptomatology. This suggests the need for optimizing monotherapy regimens before initiating polypharmacy that may not lead to improvement in symptoms. (C) 2008 Elsevier B.V. All rights reserved. C1 [Glezer, Anna] Univ Massachusetts, Massachusetts Gen Hosp, McLean Hosp, Psychiat Residency Training Program,Med Sch, Boston, MA 02114 USA. [Byatt, Nancy; Cook, Richard, Jr.; Rothschild, Anthony J.] Univ Massachusetts, Sch Med, UMass Mem Hlth Care, Boston, MA 02114 USA. [Rothschild, Anthony J.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. RP Glezer, A (reprint author), Univ Massachusetts, Massachusetts Gen Hosp, McLean Hosp, Psychiat Residency Training Program,Med Sch, 15 Parkman St,Wang 812, Boston, MA 02114 USA. EM Aglezer@partners.org; Nbyatt@verizon.net; Rothscha@ummhc.org OI Byatt, Nancy/0000-0002-4010-8919 FU University of Massachusetts Medical School FX The authors of this research paper would like to acknowledge the support staff of the Center for Psychopharmacologic Research and Treatment at the University of Massachusetts Medical School as well as those involved in the Senior Scholars Research Program at the University of Massachusetts Medical School. We would also like to thank the residents of the Psychiatry Training Program who provided patient names and data for this project. NR 13 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 2009 VL 117 IS 1-2 BP 18 EP 23 DI 10.1016/j.jad.2008.11.016 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 482PM UT WOS:000268901200002 PM 19103462 ER PT J AU Zisook, S Trivedi, MH Warden, D Lebowitz, B Thase, ME Stewart, JW Moutier, C Fava, M Wisniewski, SR Luther, J Rush, AJ AF Zisook, Sidney Trivedi, Madhukar H. Warden, Diane Lebowitz, Barry Thase, Michael E. Stewart, Jonathan W. Moutier, Christine Fava, Maurizio Wisniewski, Stephen R. Luther, James Rush, A. John TI Clinical correlates of the worsening or emergence of suicidal ideation during SSRI treatment of depression: An examination of citalopram in the STAR*D study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Major depressive disorder; Suicide; Suicidal ideation; SSRI; Treatment ID DIAGNOSTIC SCREENING QUESTIONNAIRE; SEQUENCED TREATMENT ALTERNATIVES; SEROTONIN REUPTAKE INHIBITORS; ANTIDEPRESSANT TREATMENT; PSYCHIATRIC OUTPATIENTS; RELIEVE DEPRESSION; MAJOR DEPRESSION; RISK; DISORDER; SYMPTOMATOLOGY AB Background: Untreated major depressive disorder (MOD) is a major risk factor for suicide, but some data suggest antidepressants may be associated with increased suicidal ideation (SI) in some depressed patients. The purpose of this study was to determine whether, and in whom, treatment of MDD is associated with increased or emergent SI. Methods: Patients were treated with Citalopram, 10-60 mg/day for 12-14 weeks. A score >0 on Item 12 of the Quick Inventory of Depressive Symptomatology - Self-Report indicated the presence of SI. Worsening was defined by a >= 1 point increase. Emergent SI was defined by an increase from 0 at baseline to >= 1 during treatment. Results: Of the 1909 participants with baseline SI, 57% experienced improvement in SI by their first post-baseline visit and 5% worsened. By the final visit, 74% experienced improvement and 4% worsened. Of 1721 participants without baseline SI, 7% experienced emergence by the first postbaseline visit. Of these, 63% had no SI at their final visit. Major risk factors for treatment-emergent SI at the first treatment visit were drug abuse, severe depression and melancholic features. Limitations: Main limitations are lack of a comparison group to help pinpoint whether citalopram treatment added fisk OF Protection, a placebo group to determine whether changes in SI were related to illness factors, medication effects or other factors. and more detailed and validated measures of SI. Conclusions: SI and behaviors, core features of MDD, wax and wane in intensity before, during, and perhaps after treatment. It is clinically important to understand risk factors, maintain careful surveillance and treat as vigorously as necessary to attain remission. (C) Published by Elsevier B.V. C1 [Zisook, Sidney; Lebowitz, Barry; Moutier, Christine] Univ Calif San Diego, Dept Psychiat, San Diego VA Med Ctr, San Diego, CA 92103 USA. [Trivedi, Madhukar H.; Warden, Diane; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Stewart, Jonathan W.] Columbia Univ, New York State Psychiat Inst, New York, NY USA. [Stewart, Jonathan W.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA. [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Wisniewski, Stephen R.; Luther, James] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. RP Zisook, S (reprint author), Univ Calif San Diego, Dept Psychiat, San Diego VA Med Ctr, San Diego, CA 92103 USA. EM szisook@ucsd.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU National Institute of Mental Health [N01MH90003] FX This project was funded by the National Institute of Mental Health under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (P.I.: A.J. Rush). 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 47 TC 42 Z9 43 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 2009 VL 117 IS 1-2 BP 63 EP 73 DI 10.1016/j.jad.2009.01.002 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 482PM UT WOS:000268901200008 PM 19217668 ER PT J AU Wayne, PM Hammerschlag, R Langevin, HM Napadow, V Park, JJ Schnyer, RN AF Wayne, Peter M. Hammerschlag, Richard Langevin, Helene M. Napadow, Vitaly Park, Jongbae J. Schnyer, Rosa N. TI Resolving Paradoxes in Acupuncture Research: A Roundtable Discussion SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Editorial Material ID LOW-BACK-PAIN; RANDOMIZED-TRIAL; MULTICENTER; FUTURE C1 [Hammerschlag, Richard] Oregon Coll Oriental Med, Portland, OR 97216 USA. [Wayne, Peter M.] Harvard Univ, Sch Med, Div Res & Educ Complementary & Integrat Med Thera, Tai Chi Res Program, Boston, MA USA. [Wayne, Peter M.] Harvard Univ, Sch Med, Div Res & Educ Complementary & Integrat Med Thera, Mind Body Res Program, Boston, MA USA. [Langevin, Helene M.] Univ Vermont, Dept Neurol, Burlington, VT USA. [Napadow, Vitaly] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. [Park, Jongbae J.] Univ N Carolina, Sch Med, Dept Phys Med & Rehabil, Chapel Hill, NC USA. [Schnyer, Rosa N.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. RP Hammerschlag, R (reprint author), Oregon Coll Oriental Med, 10525 SE Cherry Blossom Dr, Portland, OR 97216 USA. EM rhammerschlag@ocom.edu NR 12 TC 12 Z9 12 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD SEP PY 2009 VL 15 IS 9 BP 1039 EP 1044 DI 10.1089/acm.2009.0466 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 494XX UT WOS:000269854100016 PM 19757981 ER PT J AU Tsang, JYC Lamm, WJE Swenson, ER AF Tsang, John Y. C. Lamm, Wayne J. E. Swenson, Erik R. TI Regional CO2 tension quantitatively mediates homeostatic redistribution of ventilation following acute pulmonary thromboembolism in pigs SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE carbon dioxide; cluster analysis; distribution of ventilation; fluorescent microspheres; gas exchange ID BLOOD-FLOW; ARTERY OCCLUSION; UNILATERAL HYPOVENTILATION; INTERSTITIAL-CELLS; LUNG-MECHANICS; CARBON-DIOXIDE; RAT LUNG; MICROSPHERES; RESISTANCE; PERFUSION AB Tsang JY, Lamm WJ, Swenson ER. Regional CO2 tension quantitatively mediates homeostatic redistribution of ventilation following acute pulmonary thromboembolism in pigs. J Appl Physiol 107: 755-762, 2009. First published July 16, 2009; doi: 10.1152/japplphysiol.00245.2009.-Previous studies reported that regional CO2 tension might affect regional ventilation ((V) over dot) following acute pulmonary thromboembolism (APTE). We investigated the pathophysiology and magnitude of these changes. Eight anesthetized and ventilated piglets received autologous clots at time = 0 min until mean pulmonary artery pressure was 2.5 times baseline. The distribution of (V) over dot and perfusion ((Q) over dot) at four different times (-5, 30, 60, 120 min) was mapped by fluorescent microspheres. Regional (V) over dot and (Q) over dot were examined postmortem by sectioning the air-dried lung into 900-1,000 samples of similar to 2 cm(3) each. After the redistribution of regional (Q) over dot by APTE, but in the scenario assuming that no (V) over dot shift had yet occurred, CO2 tension in different lung regions at 30 min post-APTE (PXCO2) was estimated from the (V) over dot/(Q) over dot data and divided into four distinct clusters: i.e., PXCO2 < 10 Torr; 10 < PXCO2 < 25 Torr; 25 < PXCO2 < 50 Torr; PXCO2 > 50 Torr. Our data showed that the clusters in higher (V) over dot/(Q) over dot regions (with a PXCO2 < 25 Torr) received similar to 35% less (V) over dot when measured within 30 min of APTE, whereas, in contrast, the lower (V) over dot/(Q) over dot regions showed no statistically significant increases in their (V) over dot. However, after 30 min, there was minimal further redistribution of (V) over dot. We conclude that there are significant compensatory (V) over dot shifts out of regions of low CO2 tension soon following APTE, and that these variations in regional CO2 tension, which initiate CO2-dependent changes in airway resistance and lung parenchymal compliance, can lead to improved gas exchange. C1 [Tsang, John Y. C.] Univ British Columbia, James Hogg iCAPTURE Res Lab, Dept Med, Div Crit Care Med, Vancouver, BC V6Z 1Y6, Canada. [Lamm, Wayne J. E.; Swenson, Erik R.] Univ Washington, Dept Med, Seattle, WA USA. [Swenson, Erik R.] Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA USA. RP Tsang, JYC (reprint author), Univ British Columbia, James Hogg iCAPTURE Res Lab, Dept Med, Div Crit Care Med, 1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada. FU British Columbia Lung Association; British Columbia Heart and Stroke Foundation FX The authors thank the funding support from the British Columbia Lung Association and British Columbia Heart and Stroke Foundation. NR 38 TC 3 Z9 3 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2009 VL 107 IS 3 BP 755 EP 762 DI 10.1152/japplphysiol.00245.2009 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 488SS UT WOS:000269370700017 PM 19608933 ER PT J AU Ayers, DC Hays, PL Drew, JM Eskander, MS Osuch, D Bragdon, CR AF Ayers, David C. Hays, Peyton L. Drew, Jacob M. Eskander, Mark S. Osuch, Daniel Bragdon, Charles R. TI Two-Year Radiostereometric Analysis Evaluation of Femoral Head Penetration in a Challenging Population of Young Total Hip Arthroplasty Patients SO JOURNAL OF ARTHROPLASTY LA English DT Article DE UHMWPE; femoral head penetration; cross-linked liners ID CROSS-LINKED POLYETHYLENE; MOLECULAR-WEIGHT POLYETHYLENE; UNCEMENTED SOCKETS; ACETABULAR LINER; WEAR; PROSTHESES; MIGRATION; ACCURACY; CRACKING; LINKING AB This prospective, randomized protocol evaluated femoral head penetration after total hip arthroplasty in a young population. Forty-five patients randomly received either a cross-linked or conventional ultrahigh-molecular-weight polyethylene (UHMWPE) liner in a noncemented hemispheric cup (Trilogy, Zimmer, Warsaw, Ind) with a 28-mm femoral head. Radiostereometric analysis film pairs, Harris hip, UCLA, SF-12, and Western Ontario and McMaster Universities scores were obtained through 2 years. Median femoral head penetration was less among cross-linked compared to conventional liners as follows: 0.06 mm (0.04-0.08 mm) vs 0.08 mm (0.02-0.19 mm) at 6 months, 0.07 mm (-0.14 to 0.16 mm) vs 0.11 mm (0.01-0.27 mm) at I year, and 0.065 mm (-0.04 to 0.193 mm) vs 0.169 mm (0.09-0.22 mm) at 2 years. Clinical outcomes were similar between the groups. Highly cross-linked UHMWPE demonstrated 55% less femoral head penetration compared to conventional polyethylene at 2 years. Despite improvements in the manufacturing process and sterilization of conventional UHMWPE, the femoral head penetration rate is unchanged from historical standards. C1 [Ayers, David C.; Hays, Peyton L.; Drew, Jacob M.; Eskander, Mark S.; Osuch, Daniel] Univ Massachusetts, Sch Med, Dept Orthoped Surg & Phys Rehabil, Worcester, MA 01605 USA. [Ayers, David C.; Hays, Peyton L.; Drew, Jacob M.; Eskander, Mark S.; Osuch, Daniel] UMass Mem Healthcare Syst, Worcester, MA USA. [Bragdon, Charles R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ayers, DC (reprint author), Univ Massachusetts, Sch Med, Arthrit & Joint Replacement Ctr, Dept Orthoped & Phys Rehabil, 119 Belmont St, Worcester, MA 01605 USA. NR 22 TC 14 Z9 14 U1 0 U2 2 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 SEP PY 2009 VL 24 IS 6 BP 9 EP 14 DI 10.1016/j.arth.2009.05.027 PG 6 WC Orthopedics SC Orthopedics GA 491VD UT WOS:000269607800003 PM 19698909 ER PT J AU Huddleston, JI Maloney, WJ Wang, Y Verzier, N Hunt, DR Herndon, JH AF Huddleston, James I. Maloney, William J. Wang, Yun Verzier, Nancy Hunt, David R. Herndon, James H. TI Adverse Events After Total Knee Arthroplasty A National Medicare Study SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total knee arthroplasty; complications; mortality; adverse events; risk factors ID UNITED-STATES; HIP-ARTHROPLASTY; REPLACEMENT; OUTCOMES; OSTEOARTHRITIS; EPIDEMIOLOGY; LENGTH; STAY AB Adverse events from 2033 total knee arthroplasty patients were documented by nonphysician abstractors. The annual rate of adverse events from 2002 to 2004 was 9.2%, 6.4%, and 5.8%, respectively. Congestive heart failure (odds ratio, 2.1; 95% confidence interval, 1.2-3.5; P < .01) and chronic obstructive pulmonary disease (odds ratio, 1.8; 95% confidence interval, 1.2-2.7; P < .01) were associated with a significantly increased risk of experiencing any adverse event during the index hospitalization. The 30-day postprocedure rate of readmission for all causes was 5.5%. Experiencing an adverse event during the index hospitalization increased the length of stay (P < .001). The rate of symptomatic venous thromboembolism 30 days postprocedure was 1.7%. The 30-day postprocedure mortality rate was 0.3%. Experiencing ally adverse event was associated with an increased 30-day postprocedure mortality (P < .001). Compared with previous studies of Medicare claims, these data reveal a substantial decrease in the mortality rate, an increased readmission rate, and no substantial change in the rate of venous thromboembolism. C1 [Huddleston, James I.; Maloney, William J.] Stanford Univ, Dept Orthopaed Surg, Sch Med, Stanford, CA 94305 USA. [Wang, Yun; Verzier, Nancy] Qualidigm, Middletown, CT USA. [Hunt, David R.] Off Natl Coordinator, Dept Hlth & Human Serv, Washington, DC USA. [Herndon, James H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Huddleston, JI (reprint author), Stanford Univ, Dept Orthopaed Surg, Sch Med, 300 Pasteur Dr,R-105, Stanford, CA 94305 USA. NR 21 TC 28 Z9 28 U1 0 U2 2 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 SEP PY 2009 VL 24 IS 6 BP 95 EP 100 DI 10.1016/j.arth.2009.05.001 PG 6 WC Orthopedics SC Orthopedics GA 491VD UT WOS:000269607800020 PM 19577884 ER PT J AU Slover, J Hoffman, MV Malchau, H Tosteson, ANA Koval, KJ AF Slover, James Hoffman, Michael V. Malchau, Henrik Tosteson, Anna N. A. Koval, Kenneth J. TI A Cost-Effectiveness Analysis of the Arthroplasty Options for Displaced Femoral Neck Fractures in the Active, Healthy, Elderly Population SO JOURNAL OF ARTHROPLASTY LA English DT Article DE cost-effectiveness; femoral neck; outcomes ID TOTAL HIP-ARTHROPLASTY; INTERNAL-FIXATION; HEMIARTHROPLASTY; REPLACEMENT; MANAGEMENT; OUTCOMES; TRIAL AB This study was performed to explore the cost-effectiveness of total hip arthroplasty (THA) compared with hemiarthroplasty (HEMI) in the treatment of displaced femoral neck fractures in active otherwise healthy older patients in whom the optimum treatment is believed to be an arthroplasty procedure. A Markov decision model was used to determine whether THA or HEMI was most cost-effective for the management of a displaced femoral neck fracture in this patient population. Total I-lip arthroplasty was associated with art average cost $3000 more than HEMI, and the average quality-adjusted life year gain was 1.53. The incremental cost-effectiveness ratio associated with the THA treatment strategy is $1960 per quality-adjusted life year. Currently available data Support the use of THA as the more cost-effective treatment strategy in this specific population. The increased upfront cost appears to be offset by the improved functional results When compared with HEMI in this select patient group. C1 [Hoffman, Michael V.] Univ Utah, Dept Orthopaed, Salt Lake City, UT USA. [Koval, Kenneth J.] Dartmouth Hitchcock Med Ctr, Dept Orthopaed, Lebanon, NH 03766 USA. [Tosteson, Anna N. A.] Dartmouth Coll, Ctr Evaluat Clin Sci, Hanover, NH 03755 USA. [Slover, James; Malchau, Henrik] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Slover, J (reprint author), NYU, Hosp Joint Dis, 301 E 16th St,16th Floor, New York, NY 10003 USA. FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [P60 AR48094] FX This research was Supported in part with funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (P60 AR48094). NR 24 TC 14 Z9 20 U1 1 U2 2 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 SEP PY 2009 VL 24 IS 6 BP 854 EP 860 DI 10.1016/j.arth.2008.05.008 PG 7 WC Orthopedics SC Orthopedics GA 491VB UT WOS:000269607400004 PM 18701245 ER PT J AU Shine, KM Simson, JA Spector, M AF Shine, Kristy M. Simson, Jacob A. Spector, Myron TI Lubricin Distribution in the Human Intervertebral Disc SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SUPERFICIAL ZONE PROTEIN; VARA-PERICARDITIS SYNDROME; SURFACE MOTION; PROTEOGLYCAN-4 PRG4; ARTICULAR-CARTILAGE; MOLECULAR-STRUCTURE; REGIONAL-VARIATIONS; ANNULUS FIBROSUS; ANULUS FIBROSUS; GENE-EXPRESSION AB Background: Previous studies have identified lubricin (also known as superficial zone protein) as a lubricating glycoprotein present in several musculoskeletal tissues including articular cartilage, meniscus, and tendon. In this immunohistochemical study, we determined the presence and distribution of lubricin in the cells, extracellular matrix, and tissue surfaces of human nucleus pulposus and anulus fibrosus tissues. Methods: Twenty-eight human intervertebral discs were resected at autopsy from fourteen cadavers. Disc specimens were fixed in formalin, processed, and paraffin-em bedded prior to sectioning. Tissue sections were immunohistochemically stained for lubricin, the extent of extracellular matrix staining was evaluated semiquantitatively, and cellular staining was assessed quantitatively with use of a survey method. Results: Lubricin staining was evident in the extracellular matrix and at select surfaces of the nucleus pulposus and anulus fibrosus tissues. The extent of lubricin staining of the extracellular matrix was contingent on the disc region (nucleus pulposus, inner anulus fibrosus, or outer anulus fibrosus), with the greatest extent of matrix staining found in the nucleus pulposus, but it was not contingent on the Thompson grade. A subset of disc cells within the nucleus, inner anulus, and outer anulus also stained positively for lubricin, suggesting intrinsic cell synthesis of the glycoprotein. The disc region significantly affected the percentage of lubricin-staining cells, with the greatest percentage of cells staining for lubricin (nearly 10%) found in the nucleus pulposus. The percentage of cells staining for lubricin correlated with the extent of extracellular matrix staining for lubricin. Conclusions: The results of this study confirm the presence of lubricin in the human intervertebral disc and demonstrate a unique distribution compared with that in the goat. The presence of lubricin in asymptomatic discs provides a foundation for future research regarding the role of lubricin in pathological disc conditions. C1 [Shine, Kristy M.] VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. RP Shine, KM (reprint author), VA Boston Healthcare Syst, Tissue Engn, 150 S Huntington Ave,MS 151, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU Department of Veterans Affairs; National Science Foundation FX In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the Department of Veterans Affairs and the National Science Foundation. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated. NR 39 TC 16 Z9 16 U1 1 U2 2 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 2009 VL 91A IS 9 BP 2205 EP 2212 DI 10.2106/JBJS.H.01344 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 489XS UT WOS:000269460400018 PM 19723998 ER PT J AU Stoddard, FJ Sorrentino, EA Ceranoglu, TA Saxe, G Murphy, JM Drake, JE Ronfeldt, H White, GW Kagan, J Snidman, N Sheridan, RL Tompkins, RG AF Stoddard, Frederick J., Jr. Sorrentino, Erica A. Ceranoglu, T. Atilla Saxe, Glenn Murphy, J. Michael Drake, Jennifer E. Ronfeldt, Heidi White, Gwyne W. Kagan, Jerome Snidman, Nancy Sheridan, Robert L. Tompkins, Ronald G. TI Preliminary Evidence for the Effects of Morphine on Posttraumatic Stress Disorder Symptoms in One- to Four-Year-Olds With Burns SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID NORADRENALINE RELEASE; BRAIN-REGIONS; CHILDREN; PTSD; RAT; HYPOALGESIA; AMYGDALA; TRAUMA; FEAR AB This study tested the hypothesis that very young children who received more morphine for acute burns would have larger decreases in posttraumatic symptoms 3 to 6 months later. This has never before been studied in very young children, despite the high frequency of burns and trauma in this age group. Seventy 12- to 48-month-old nonvented children with acute burns admitted to a major pediatric burn center and their parents participated. Parents were interviewed at three time points: during their child's hospitalization, 1 month, and 3 to 6 months after discharge. Measures included the Child Stress Disorders Checklist - Burn Version (CSDC-B). Chart reviews were conducted to obtain children's morphine dosages during hospitalization. Mean equivalency dosages of morphine (mg/kg/d) were calculated to combine oral and intravenous administrations. Eleven participants had complete 3 to 6-month data on the CSDC. The correlation between average morphine dose and amount of decrease in posttraumatic stress disorder symptoms on the CSDC (r = -0.32) was similar to that found in studies with older children. The correlation between morphine dose and amount of decrease in symptoms on the arousal cluster of the CSDC was significant (r = -0.63, P < .05). Findings from the current study suggest that, for young children, management of pain with higher doses of morphine may be associated with a decreasing number of posttraumatic stress disorder symptoms, especially those of arousal, in the months after major trauma. This extends, with very young children, the previous findings with 6- to 16-year olds. (J Burn Care Res 2009;30:836-843) C1 [Stoddard, Frederick J., Jr.; Sorrentino, Erica A.; Ceranoglu, T. Atilla; Saxe, Glenn; Murphy, J. Michael; Drake, Jennifer E.; Ronfeldt, Heidi; White, Gwyne W.; Sheridan, Robert L.; Tompkins, Ronald G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Stoddard, Frederick J., Jr.; Sorrentino, Erica A.; Ceranoglu, T. Atilla; Saxe, Glenn; Murphy, J. Michael; Drake, Jennifer E.; Ronfeldt, Heidi; White, Gwyne W.; Sheridan, Robert L.; Tompkins, Ronald G.] Shriners Hosp Children, Boston, MA USA. [Saxe, Glenn] Childrens Hosp Boston, Boston, MA USA. [Kagan, Jerome; Snidman, Nancy] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Stoddard, FJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, SBH 610,55 Fruit St, Boston, MA 02114 USA. OI Saxe, Glenn/0000-0002-4756-1169 FU Shriners Hospitals for Children [8760] FX Supported by the Shriners Hospitals for Children (grant no. 8760). NR 27 TC 45 Z9 45 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD SEP-OCT PY 2009 VL 30 IS 5 BP 836 EP 843 DI 10.1097/BCR.0b013e3181b48102 PG 8 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 494YP UT WOS:000269856100012 PM 19692914 ER PT J AU Ganz, PA Land, SR Antonio, C Zheng, P Yothers, G Petersen, L Wickerham, DL Wolmark, N Ko, CY AF Ganz, Patricia A. Land, Stephanie R. Antonio, Cynthia Zheng, Ping Yothers, Greg Petersen, Laura Wickerham, D. Lawrence Wolmark, N. Ko, Clifford Y. TI Cancer survivorship research: the challenge of recruiting adult long term cancer survivors from a cooperative clinical trials group SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE LA English DT Article DE Colorectal cancer survivors; Clinical trials; Recruitment barriers ID QUALITY-OF-LIFE; ADVANCED HODGKIN DISEASE; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; ONCOLOGY-GROUP; WOMEN; MODEL AB Introduction With the growing number of adult cancer survivors, there is increasing need for information that links potential late and long term effects with specific treatment regimens. Few adult cancer patients are treated on clinical trials; however, patients previously enrolled in these trials are an important source of information about treatment-related late effects. Methods Focusing on colorectal cancer survivors, we used the database from five phase III randomized clinical trials from the National Surgical Adjuvant Breast & Bowel Project (NSABP) to recruit and enroll long term survivors in a study of late health outcomes and quality of life. We describe the challenges to recruitment of patients more than 5 -20 years after treatment. Results Sixty-five NSABP treatment sites were invited to enroll patients in the study. Sixty participated with the potential to recruit 2,408 patients. We received registration forms on only 976 patients (41%) of whom 744 (76%) expressed interest in participating and 708 completed interviews (95% of those expressing interest; 29% of total potential sample). There were multiple barriers to recruitment (difficulty locating patients, lack of institutional commitment, lack of patient interest). Conclusions Patients treated on clinical trials are an important potential source for examining the late effects of cancer treatments. Retrospective recruitment has substantial limitations. In the future, mechanisms should be established for prospective long-term follow-up to identify and understand the frequency and type of late effects associated with cancer treatments. Implications for Cancer Survivors As cancer patients are living longer, it will be important to learn from participants in clinical trials whether or not specific treatment regimens are associated with any serious late effects. C1 [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Ganz, Patricia A.; Antonio, Cynthia; Petersen, Laura; Ko, Clifford Y.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. [Land, Stephanie R.; Zheng, Ping; Yothers, Greg] Natl Surg Adjuvant Breast & Bowel Project NSABP, Ctr Biostat, Pittsburgh, PA USA. [Land, Stephanie R.; Yothers, Greg] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Wickerham, D. Lawrence; Wolmark, N.] Natl Surg Adjuvant Breast & Bowel Project NSABP, Operat Ctr, Pittsburgh, PA USA. [Wickerham, D. Lawrence; Wolmark, N.] Allegheny Gen Hosp, Dept Human Oncol, Pittsburgh, PA 15212 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. RP Ganz, PA (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. EM pganz@mednet.ucla.edu OI Yothers, Greg/0000-0002-7965-7333 FU American Cancer Society [RSGPB-05-236-01-CPPB]; National Cancer Institute, Department of Health and Human Services [U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974] FX We thank the staff at the NSABP Operations Center (Barbara Harkins, RN and Teresa Bradley, PhD), the NSABP clinical site coordinators and physicians, and the patients who participated in this study. This research was funded by the American Cancer Society grant RSGPB-05-236-01-CPPB, and through Public Health Service Grants U10-CA-12027, U10-CA-69651, U10-CA-37377, and U10-CA-69974 from the National Cancer Institute, Department of Health and Human Services. NR 19 TC 22 Z9 22 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD SEP PY 2009 VL 3 IS 3 BP 137 EP 147 DI 10.1007/s11764-009-0093-2 PG 11 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA V17XR UT WOS:000207970400001 PM 19526347 ER PT J AU Latka, RN Alvarez-Reeves, M Cadmus, L Irwin, ML AF Latka, Rebecca N. Alvarez-Reeves, Marty Cadmus, Lisa Irwin, Melinda L. TI Adherence to a randomized controlled trial of aerobic exercise in breast cancer survivors: the Yale exercise and survivorship study SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE LA English DT Article DE Physical activity; Fitness; Survival; Recurrence; Obesity; Weight; Behavior; Diet ID PHYSICAL-ACTIVITY LEVELS; LIFE-STYLE FACTORS; WEIGHT-GAIN; POSTMENOPAUSAL WOMEN; DIAGNOSIS; HEALTH; CHEMOTHERAPY; OBESITY; FAT AB Purpose To examine predictors of exercise adherence in breast cancer survivors. Methods Seventy-five breast cancer survivors were randomly assigned to exercise (n=37) or usual care (n=38). Demographic, prognostic, physiologic, and psychosocial information was collected at baseline and 6 months. The exercise goal was 30 min of exercise 5 days/week for 6 months. Results Women randomized to exercise participated in moderate-intensity recreational exercise for 123 +/- 52 min/week (81% of the prescribed 150 min/week) over 6 months. Baseline variables associated with better adherence were lower body mass index (BMI), smaller waist circumference, higher amounts of physical activity 6 months prior to enrollment, being in the preparation vs. contemplation Stage of Change and higher FACT-B breast cancer subscale score. After adjusting for these variables, lower BMI and higher Stage of Change continued to be associated with better adherence (p<0.05). Conclusions Future studies of exercise and breast cancer prognosis should target obese women for participation, as well as women just beginning to contemplate participation and its benefits after a cancer diagnosis. C1 [Irwin, Melinda L.] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, New Haven, CT 06520 USA. [Alvarez-Reeves, Marty] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cadmus, Lisa] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Irwin, ML (reprint author), Yale Univ, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, POB 208034, New Haven, CT 06520 USA. EM melinda.irwin@yale.edu OI Franckle, Rebecca/0000-0002-4327-9764 FU American Cancer Society [MRSG-04-006-01-CPPB]; Susan G. Komen Breast Cancer Foundation [BCTR0201916]; National Center of Research Resources, National Institutes of Health [M01-RR00125] FX American Cancer Society (MRSG-04-006-01-CPPB) and the Susan G. Komen Breast Cancer Foundation (BCTR0201916). Supported in part by a General Clinical Research Center grant from the National Center of Research Resources, National Institutes of Health (Grant # M01-RR00125) awarded to Yale University School of Medicine NR 40 TC 27 Z9 28 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD SEP PY 2009 VL 3 IS 3 BP 148 EP 157 DI 10.1007/s11764-009-0088-z PG 10 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA V17XR UT WOS:000207970400002 PM 19626443 ER PT J AU Jones, R Capen, DE Jacobson, M Cohen, KS Scadden, DT Duda, DG AF Jones, Rosemary Capen, Diane E. Jacobson, Margaretha Cohen, Kenneth S. Scadden, David T. Duda, Dan G. TI VEGFR2+PDGFR beta plus circulating precursor cells participate in capillary restoration after hyperoxia acute lung injury (HALI) SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE hyperoxia; lung capillary injury; restoration; circulating precursor cell ID PROGENITOR CELLS; PULMONARY-HYPERTENSION; BONE-MARROW; NEOVASCULARIZATION MODEL; ANGIOGENESIS; CONTRIBUTE; MOLECULES; PROTOCOL; RODENTS; REPAIR AB The in vivo morphology and phenotype of circulating cells that spontaneously contribute to new vessel formation in adults remain unclear. Here, we use high-resolution imaging and flow cytometry to characterize the morphology and phenotype of a distinct population of circulating mononuclear cells contributing to spontaneous new vessel formation after hyperoxia acute lung injury (HALI). We identify a subpopulation of myeloid (CD11b/Mac1+) haematopoietic cells co-expressing vascular endothelial growth factor receptor 2 (VEGFR2) and platelet derived growth factor receptor beta (PDGFR beta). Moreover, we show that these CD11b+VEGFR2+PDGFR beta+ circulating precursor cells (CPCs) contribute structurally to the luminal surface of capillaries re-forming 2 weeks post-HALI. This indicates that these myeloid CPCs may function, at least transiently, as putative vascular precursors, and has important implications for capillary growth and repair in injury and in pathologies of the lung and other organs. C1 [Jones, Rosemary; Capen, Diane E.; Jacobson, Margaretha; Cohen, Kenneth S.; Scadden, David T.; Duda, Dan G.] Harvard Univ, Sch Med, Boston, MA USA. [Jones, Rosemary; Capen, Diane E.; Jacobson, Margaretha] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Cohen, Kenneth S.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Duda, Dan G.] Massachusetts Gen Hosp, Steele Lab, Boston, MA 02114 USA. RP Jones, R (reprint author), CNY-3416,Bldg 149,13th St, Charlestown, MA 02129 USA. EM rcjones@partners.org; duda@steele.mgh.harvard.edu FU NIH [R01-HL070866, R01-HL089252, R01-CA115767, P01-CA80124, R01-CA85140, R01-CA126642, K08-HL071938] FX The work of the authors is supported by grants from the NIH (R01-HL070866, R01-HL089252, R01-CA115767, P01-CA80124, R01-CA85140, R01-CA126642, K08-HL071938 and a Federal Share/NCI Proton Beam Program Income Grant). We thank Dr LL Munn for help with quantitative measurements and C Koppel for technical support. NR 20 TC 10 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1582-4934 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD SEP PY 2009 VL 13 IS 9B BP 3720 EP 3729 DI 10.1111/j.1582-4934.2009.00785.x PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 551BC UT WOS:000274179300064 PM 19426150 ER PT J AU Singh, I Singh, AK Contreras, MA AF Singh, Inderjit Singh, Avtar K. Contreras, Miguel A. TI Peroxisomal Dysfunction in Inflammatory Childhood White Matter Disorders: An Unexpected Contributor to Neuropathology SO JOURNAL OF CHILD NEUROLOGY LA English DT Article; Proceedings Paper CT 8th Neurobiology of Disease in Children Symposium CY NOV 05, 2008 CL Santa Clara, CA DE inflammation; leukodystrophies; myelin; neuroinflammation; peroxisomal disorders; periventricular leukomalacia ID X-LINKED ADRENOLEUKODYSTROPHY; GLOBOID-CELL LEUKODYSTROPHY; ACTIVATED-RECEPTOR-ALPHA; DEVELOPING RAT-BRAIN; CHAIN FATTY-ACIDS; N-ACETYL CYSTEINE; C6 GLIAL-CELLS; OXIDATIVE STRESS; TWITCHER MOUSE; TNF-ALPHA AB The peroxisome, an ubiquitous subcellular organelle, plays an important function in Cellular metabolism, and its importance for human health is underscored by the identification of fatal disorders caused by genetic abnormalities. Recent findings indicate that peroxisomal dysfunction is not only restricted to inherited peroxisomal diseases but also to disease processes associated with generation of inflammatory mediators that downregulate cellular peroxisomal homeostasis. Evidence indicates that leukodystrophies (i.e. X-linked adrenoleukodystrophy, globoid cell leukodystrophy, and periventricular leukomalacia) may share common denominators in the development and progression of the inflammatory process and thus in the dysfunctions of peroxisomes. Dysfunctions of peroxisomes may therefore contribute in part to white matter disease and to the mental and physical disabilities that develop in patients affected by these diseases. C1 [Singh, Inderjit; Contreras, Miguel A.] Med Univ S Carolina, Charles P Darby Childrens Res Inst, Dept Pediat, Div Dev Neurogenet, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson Vet Adm Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Charles P Darby Childrens Res Inst, Dept Pediat, Div Dev Neurogenet, 173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS-22576, R01 NS034741, NS-34741, R01 NS040810, 5R13NS040925-09, R01 NS022576, R01 NS022576-26, R13 NS040925, R37 NS022576, R01 NS037766, NS-40810, NS-37766] NR 72 TC 12 Z9 12 U1 0 U2 0 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 SEP PY 2009 VL 24 IS 9 BP 1147 EP 1157 DI 10.1177/0883073809338327 PG 11 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 489DF UT WOS:000269399200010 PM 19605772 ER PT J AU Shaw, ND Srouji, SS Histed, SN McCurnin, KE Hall, JE AF Shaw, Natalie D. Srouji, Serene S. Histed, Stephanie N. McCurnin, Kristin E. Hall, Janet E. TI Aging Attenuates the Pituitary Response to Gonadotropin-Releasing Hormone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; SUBUNIT GENE-EXPRESSION; OLD MALE-RATS; LUTEINIZING-HORMONE; POSTMENOPAUSAL WOMEN; LH-SECRETION; HOMOLOGOUS REGULATION; HYPOTHALAMIC FUNCTION; DIFFERENTIAL CONTROL; ANTERIOR-PITUITARY AB Context: Complex changes in GnRH secretion occur with aging in women, but little is known about the effect of aging on the pituitary per se. Objective: The aim of the study was to determine whether pituitary responsiveness to GnRH is attenuated with aging. Design and Setting: A GnRH antagonist and graded doses of GnRH were used to isolate pituitary responsiveness in Clinical Research Center studies at an academic medical center. Subjects: Subjects were healthy postmenopausal women (PMW) aged 48-57 yr (n = 10) or 70-77 yr (n = 9). Interventions: A suppressive dose of the NAL-GLU GnRH antagonist (150 mu g/kg sc) was administered and was followed by GnRH doses of 25, 75, 250, or 750 ng/kg iv every 4 h. Results: The LH response to GnRH was attenuated with aging (P = 0.05) with an interaction between age and dose (P = 0.01) such that the LH amplitude was less in older PMW at the higher doses (250 ng/kg, 50 +/- 9 vs. 29 +/- 4.9 IU/liter, for young and old PMW, respectively, P = 0.02; and 750 ng/kg, 97.7 +/- 11 vs. 70.2 +/- 9.3 IU/liter, P = 0.002), but not the lower doses of GnRH. The FSH response to GnRH was also attenuated with aging in PMW (P = 0.005). Conclusions: In studies that isolated the pituitary from endogenous GnRH stimulation, aging attenuated the LH and FSH responses to exogenous GnRH in PMW. These studies indicate that the pituitary plays a role in the decline in gonadotropin levels with aging, further supporting the potential contribution of age-associated changes in both hypothalamic and pituitary function to reproductive senescence. (J Clin Endocrinol Metab 94: 3259-3264, 2009) C1 [Shaw, Natalie D.; Srouji, Serene S.; Histed, Stephanie N.; McCurnin, Kristin E.; Hall, Janet E.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Shaw, Natalie D.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX-5,55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org OI Shaw, Natalie/0000-0002-0847-9170 FU National Institutes of Health (NIH) [R01 AG13241, M01 RR1066.]; NIH [5T32 HD007396] FX This work was supported by National Institutes of Health (NIH) Grants R01 AG13241 and M01 RR1066. N. D. S. received fellowship support from the NIH (5T32 HD007396). NR 46 TC 18 Z9 19 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2009 VL 94 IS 9 BP 3259 EP 3264 DI 10.1210/jc.2009-0526 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491NB UT WOS:000269584600018 PM 19549740 ER PT J AU Pihlajamaki, J Boes, T Kim, EY Dearie, F Kim, BW Schroeder, J Mun, E Nasser, I Park, PJ Bianco, AC Goldfine, AB Patti, ME AF Pihlajamaeki, Jussi Boes, Tanner Kim, Eun-Young Dearie, Farrell Kim, Brian W. Schroeder, Joshua Mun, Edward Nasser, Imad Park, Peter J. Bianco, Antonio C. Goldfine, Allison B. Patti, Mary Elizabeth TI Thyroid Hormone-Related Regulation of Gene Expression in Human Fatty Liver SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ACTIVATED PROTEIN-KINASE; NONALCOHOLIC STEATOHEPATITIS; INSULIN-RESISTANCE; IN-VIVO; OXIDATIVE-METABOLISM; HEPATIC STEATOSIS; OBESE MICE; RECEPTOR; TYPE-2; DISEASE AB Context: Fatty liver is an important complication of obesity; however, regulatory mechanisms mediating altered gene expression patterns have not been identified. Objective: The aim of the study was to identify novel transcriptional changes in human liver that could contribute to hepatic lipid accumulation and associated insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis. Design: We evaluated gene expression in surgical liver biopsies from 13 obese (nine with type 2 diabetes) and five control subjects using Affymetrix U133A microarrays. PCR validation was performed in liver biopsies using an additional 16 subjects. We also tested thyroid hormone responses in mice fed chow or high-fat diet. Setting: Recruitment was performed in an academic medical center. Participants: Individuals undergoing elective surgery for obesity or gallstones participated in the study. Results: The top-ranking gene set, down-regulated in obese subjects, was comprised of genes previously demonstrated to be positively regulated by T(3) in human skeletal muscle (n = 399; P < 0.001; false discovery rate = 0.07). This gene set included genes related to RNA metabolism (SNRPE, HNRPH3, TIA1, and SFRS2), protein catabolism (PSMA1, PSMD12, USP9X, IBE2B, USP16, and PCMT1), and energy metabolism (ATP5C1, COX7C, UQCRB). We verified thyroid hormone regulation of these genes in the liver after injection of C57BL/6J mice with T(3) (100 mu g/100 g body weight); furthermore, T(3)-induced increases in expression of these genes were abolished by high-fat diet. In agreement, expression of these genes inversely correlated with liver fat content in humans. Conclusions: These data suggest that impaired thyroid hormone action may contribute to altered patterns of gene expression in fatty liver. (J Clin Endocrinol Metab 94: 3521-3529, 2009) C1 [Pihlajamaeki, Jussi; Boes, Tanner; Kim, Eun-Young; Dearie, Farrell; Schroeder, Joshua; Goldfine, Allison B.; Patti, Mary Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Kim, Brian W.; Mun, Edward; Bianco, Antonio C.] Brigham & Womens Hosp, Boston, MA 02215 USA. [Mun, Edward] Faulkner Hosp Partners HealthCare, Boston, MA 02130 USA. [Nasser, Imad] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Park, Peter J.] Childrens Hosp, Boston, MA 02215 USA. [Pihlajamaeki, Jussi; Kim, Eun-Young; Kim, Brian W.; Mun, Edward; Nasser, Imad; Park, Peter J.; Bianco, Antonio C.; Goldfine, Allison B.; Patti, Mary Elizabeth] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl,Room 620, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu RI Bianco, Antonio/A-4965-2008 OI Bianco, Antonio/0000-0001-7737-6813 FU National Institutes of Health [DK062948, DK060837, DK70648, M01 RR001032, D36836]; Diabetes Genome Anatomy Project; Graetz Family Foundation; General Clinical Research Center; Diabetes and Endocrinology Research Center; Joslin Diabetes Center; Sigrid Juselius Foundation; Maud Kuistila Foundation; Northern Savo Cultural Foundation; Viipuri Tuberculosis Foundation FX This work was supported by National Institutes of Health Grants DK062948 (to M. E. P.) and DK060837 (Diabetes Genome Anatomy Project, to M. E. P. and A. B. G.), DK70648 (to A. B. G.), M01 RR001032 (General Clinical Research Center), and D36836 (to Diabetes and Endocrinology Research Center, Joslin Diabetes Center). J. P. also received support from the Sigrid Juselius Foundation, Maud Kuistila Foundation, Northern Savo Cultural Foundation, and Viipuri Tuberculosis Foundation. NR 40 TC 52 Z9 56 U1 0 U2 3 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 SEP PY 2009 VL 94 IS 9 BP 3521 EP 3529 DI 10.1210/jc.2009-0212 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491NB UT WOS:000269584600052 PM 19549744 ER PT J AU Tsai, CL Camargo, CA AF Tsai, Chu-Lin Camargo, Carlos A., Jr. TI Methodological considerations, such as directed acyclic graphs, for studying "acute on chronic" disease epidemiology: Chronic obstructive pulmonary disease example SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Acute exacerbation; Casual inference; Chronic obstructive pulmonary disease; Epidemiological methods; Number needed to treat; Statistics ID BODY-MASS INDEX; QUALITY-OF-LIFE; MARGINAL STRUCTURAL MODELS; RANDOMIZED CONTROLLED-TRIALS; EMERGENCY-DEPARTMENT VISITS; CASE-CROSSOVER DESIGN; RECURRENT EVENTS; HEALTH-STATUS; STATISTICAL TREATMENT; CLINICAL USEFULNESS AB Objective: Acute exacerbations of chronic disease are ubiquitous in clinical medicine, and thus far, there has been a paucity of integrated methodological discussion on this phenomenon. Study Design and Setting: We use acute exacerbations of chronic obstructive pulmonary disease as an example to emphasize key epidemiological and statistical issues for this understudied field in clinical epidemiology. Results: Directed acyclic graphs are a useful epidemiological tool to explain the differential effects of risk factor on health outcomes in studies of acute and chronic phases of disease. To study the pathogenesis of acute exacerbations of chronic disease, case-crossover design and time-series analysis are well-suited study designs to differentiate acute and chronic effect. Modeling changes over time and setting appropriate thresholds are important steps to separate acute from chronic phases of disease in serial measurements. In statistical analysis, acute exacerbations are recurrent events, and some individuals are more prone to recurrences than others. Therefore, appropriate statistical modeling should take into account intraindividual dependence. Finally, we recommend the use of "event-based" number needed to treat (NNT) to prevent a single exacerbation instead of traditional patient-based NNT. Conclusion: Addressing these methodological challenges will advance research quality in acute on chronic disease epidemiology. (C) 2009 Elsevier Inc. All rights reserved. C1 [Tsai, Chu-Lin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,EMNet Coordinating Ctr, Boston, MA 02114 USA. [Tsai, Chu-Lin; Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. RP Tsai, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 NR 73 TC 17 Z9 17 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD SEP PY 2009 VL 62 IS 9 BP 982 EP 990 DI 10.1016/j.jclinepi.2008.10.005 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 481QT UT WOS:000268827300011 PM 19211222 ER PT J AU Massie, BM AF Massie, Barry M. TI Prevention of Heart Failure With Chlorthalidone in ALLHAT: Placing the Results Into Perspective SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; JOINT NATIONAL COMMITTEE; HIGH BLOOD-PRESSURE; 7TH REPORT; OUTCOMES; HYPERTENSION; AMLODIPINE; DIURETICS; MORTALITY C1 [Massie, Barry M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Massie, Barry M.] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA USA. RP Massie, BM (reprint author), Cardiol 111C,4150 Clement St, San Francisco, CA USA. EM barry.massie@va.gov NR 15 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD SEP PY 2009 VL 11 IS 9 BP 462 EP 465 DI 10.1111/j.1751-7176.2009.00169.x PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 492ZQ UT WOS:000269702600002 PM 19751457 ER PT J AU Rozansky, DJ Cornwall, T Subramanya, AR Rogers, S Yang, YF David, LL Zhu, XM Yang, CL Ellison, DH AF Rozansky, David J. Cornwall, Tonya Subramanya, Arohan R. Rogers, Shaunessy Yang, Yong-Feng David, Larry L. Zhu, Xiaoman Yang, Chao-Ling Ellison, David H. TI Aldosterone mediates activation of the thiazide-sensitive Na-Cl cotransporter through an SGK1 and WNK4 signaling pathway SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BLOOD-PRESSURE; NEDD4-2 PHOSPHORYLATION; MOLECULAR PATHOGENESIS; COLLECTING DUCT; SODIUM-CHLORIDE; INDUCED PROTEIN; ANGIOTENSIN-II; KINASE DOMAIN; IN-VIVO; TRANSPORT AB Aldosterone regulates volume homeostasis and blood pressure by enhancing sodium reabsorption in the kidney's distal nephron (DN). On the apical. surface of these renal epithelia, aldosterone increases expression and activity of the thiazide-sensitive Na-Cl cotransporter (NCC) and the epithelial sodium channel (ENaC). While the cellular mechanisms by which aldosterone regulates ENaC have been well characterized, the molecular mechanisms that link aldosterone to NCC-mediated Na(+)/Cl(-) reabsorption remain elusive. The serine/threonine kinase with-no-lysine 4 (WNK4) has previously been shown to reduce cell surface expression of NCC. Here we measured sodium uptake in a Xenopus oocyte expression system and found that serum and glucocorticoid-induced kinase 1 (SGK1), an aldosterone-responsive gene expressed in the DN, attenuated the inhibitory effect of WNK4 on NCC activity. In addition, we showed - both in vitro and in a human kidney cell line - that SGK1 bound and phosphorylated WNK4. We found one serine located within an established SGK1 consensus target sequence, and the other within a motif that was, to our knowledge, previously uncharacterized. Mutation of these target serines to aspartate, in order to mimic phosphorylation, attenuated the effect of WNK4 on NCC activity in the Xenopus oocyte system. These data thus delineate what we believe to be a novel mechanism for aldosterone activation of NCC through SGK1 signaling of WNK4 kinase. C1 [Rozansky, David J.; Cornwall, Tonya; Yang, Yong-Feng] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. [Subramanya, Arohan R.; Rogers, Shaunessy; Zhu, Xiaoman; Yang, Chao-Ling; Ellison, David H.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Subramanya, Arohan R.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Subramanya, Arohan R.] Univ Maryland, Dept Physiol, Baltimore, MD 21201 USA. [David, Larry L.] Oregon Hlth & Sci Univ, Dept Biochem, Portland, OR 97201 USA. [Ellison, David H.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Ellison, David H.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97201 USA. [Ellison, David H.] Portland VA Med Ctr, Portland, OR USA. RP Rozansky, DJ (reprint author), 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM rozansky@ohsu.edu OI Ellison, David/0000-0003-2915-265X FU NIH [KO8, RO1 051496 11, SP30CA069533, SP30EY010572]; NIDDK [02723] FX This work was supported by the following grants: NIH KO8 NIDDK 02723, NIH RO1 051496 11, the National Kidney Foundation, and NIH Core Grants SP30CA069533 and SP30EY010572. NR 52 TC 92 Z9 96 U1 1 U2 9 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 SEP PY 2009 VL 119 IS 9 BP 2601 EP 2612 DI 10.1172/JCI38323 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 493BR UT WOS:000269708600021 PM 19690383 ER PT J AU Kim, JY Ferraro, MJ Branda, JA AF Kim, Ji Yeon Ferraro, Mary Jane Branda, John A. TI False-Negative Results Obtained with the Gen-Probe Amplified Mycobacterium tuberculosis Direct Test Caused by Unrecognized Inhibition of the Amplification Reaction SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID EXTRAPULMONARY SPECIMENS; RESPIRATORY SPECIMENS; PERFORMANCE; COMPLEX AB The Gen-Probe Amplified Mycobacterium tuberculosis direct test is widely used in the diagnosis of tuberculosis. Specimens may contain amplification inhibitors, potentially leading to false-negative results if unrecognized. We report a failure to detect inhibition, despite adherence to the inhibition testing guidelines provided on the label, and recommend changes. C1 [Kim, Ji Yeon; Ferraro, Mary Jane; Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Branda, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, GRB 526 Microbiol,55 Fruit St, Boston, MA 02114 USA. EM Branda.John@mgh.harvard.edu NR 19 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2009 VL 47 IS 9 BP 2995 EP 2997 DI 10.1128/JCM.00966-09 PG 3 WC Microbiology SC Microbiology GA 489RL UT WOS:000269439600047 PM 19587300 ER PT J AU Mahlen, SD Clarridge, JE AF Mahlen, Steven D. Clarridge, Jill E., III TI Thumb Infection Caused by Streptococcus pseudoporcinus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PORCINUS; IDENTIFICATION AB Streptococcus pseudoporcinus, a recently described organism found in the genitourinary tract of women, was isolated from a thumb wound in a male patient subsequent to trauma. This case describes a rarely reported non-genitourinary tract clinical isolate of S. pseudoporcinus. C1 [Mahlen, Steven D.] Univ Washington, Dept Lab Med, USA, Seattle, WA 98195 USA. [Clarridge, Jill E., III] VA Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA 98108 USA. RP Clarridge, JE (reprint author), VA Puget Sound Hlth Care Syst, Pathol & Lab Med Serv 113, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Jill.clarridge@va.gov NR 14 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2009 VL 47 IS 9 BP 3041 EP 3042 DI 10.1128/JCM.00802-09 PG 2 WC Microbiology SC Microbiology GA 489RL UT WOS:000269439600062 PM 19571017 ER PT J AU Morrow, M Harris, JR AF Morrow, Monica Harris, Jay R. TI More Mastectomies: Is This What Patients Really Want? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID INVASIVE BREAST-CARCINOMA; PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; CANCER; RECURRENCE; ACCURACY; SURGERY; THERAPY; TRIAL; WOMEN C1 [Morrow, Monica] Mem Sloan Kettering Canc Ctr, Dept Surg, Breast Surg Serv, New York, NY 10021 USA. [Harris, Jay R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. RP Morrow, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Breast Surg Serv, 1275 York Ave, New York, NY 10021 USA. NR 19 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2009 VL 27 IS 25 BP 4038 EP 4040 DI 10.1200/JCO.2009.23.0078 PG 3 WC Oncology SC Oncology GA 488WN UT WOS:000269381100002 PM 19635996 ER PT J AU Efstathiou, JA Bae, K Shipley, WU Kaufman, DS Hagan, MP Heney, NM Sandler, HM AF Efstathiou, Jason A. Bae, Kyounghwa Shipley, William U. Kaufman, Donald S. Hagan, Michael P. Heney, Niall M. Sandler, Howard M. TI Late Pelvic Toxicity After Bladder-Sparing Therapy in Patients With Invasive Bladder Cancer: RTOG 89-03, 95-06, 97-06, 99-06 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; SELECTIVE ORGAN PRESERVATION; TRANSITIONAL-CELL CARCINOMA; COMBINED-MODALITY TREATMENT; LONG-TERM SURVIVORS; ONCOLOGY GROUP; RADICAL CYSTECTOMY; RADIATION-THERAPY; NEOADJUVANT CHEMOTHERAPY; DISTRESSFUL SYMPTOMS AB Purpose In selected patients with muscle-invasive bladder cancer, combined-modality therapy (transurethral resection bladder tumor [TURBT], radiation therapy, chemotherapy) with salvage cystectomy, if necessary, can achieve survival rates similar to radical cystectomy. We investigated late pelvic toxicity after chemoradiotherapy for patients treated on prospective protocols. Patients and Methods Between 1990 and 2002, 285 eligible patients enrolled on four prospective protocols (Radiation Therapy Oncology Group [RTOG] 8903, 9506, 9706, 9906) and 157 underwent combined-modality therapy, surviving >= 2 years from start of treatment with their bladder intact. Rates of late genitourinary (GU) and GI toxicity were assessed using the RTOG Late Radiation Morbidity Schema, with worst toxicity grade (scale 0 to 5) occurring >= 180 days after start of consolidation therapy reported for each patient. Persistence of toxicity was defined as grade 3+ toxicity not decreasing by at least one grade. Logistic and Cox regression analyses were performed to evaluate relationship between clinical characteristics, frequency, and time to late grade 3+ pelvic toxicity. Covariates included age, sex, stage, presence of carcinoma in situ, completeness of TURBT, and protocol. Results Median follow-up was 5.4 years (range, 2.0 to 13.2 years). Seven percent of patients experienced late grade 3+ pelvic toxicity: 5.7% GU and 1.9% GI. In only one of nine patients did a grade 3+ GU toxicity persist. Notably there were no late grade 4 toxicities and no treatment-related deaths. None of the clinical variables studied predicted for late grade 3+ pelvic toxicity. Conclusion Rates of significant late pelvic toxicity for patients completing combined-modality therapy for invasive bladder cancer and retaining their native bladder are low. C1 [Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA USA. Radiat Therapy Oncol Grp, Dept Stat, Philadelphia, PA USA. Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org FU National Cancer Institute [RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115] FX Supported by Grants No. RTOG U10 CA21661, CCOP U10 CA37422, and Stat U10 CA32115 from the National Cancer Institute. This manuscript's contents are the sole responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 31 TC 74 Z9 75 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2009 VL 27 IS 25 BP 4055 EP 4061 DI 10.1200/JCO.2008.19.5776 PG 7 WC Oncology SC Oncology GA 488WN UT WOS:000269381100006 PM 19636019 ER PT J AU Pirl, WF Greer, J Temel, JS Yeap, BY Gilman, SE AF Pirl, William F. Greer, Joseph Temel, Jennifer S. Yeap, Beow Y. Gilman, Stephen E. TI Major Depressive Disorder in Long-Term Cancer Survivors: Analysis of the National Comorbidity Survey Replication SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; TESTICULAR CANCER; COLORECTAL-CANCER; BREAST-CANCER; NCS-R; HEALTH; POPULATION; DIAGNOSIS; SYMPTOMS; SUICIDE AB Purpose Prior research is mixed as to whether long-term cancer survivors (LCSs) have higher rates of depression than the general population. This is the first study to compare the rates of major depressive disorder (MDD) between LCSs and people without cancer histories in a nationally representative cross-sectional multistage cluster survey sample, the National Comorbidity Survey-Replication (NCS-R). Methods Between 2001 and 2003, face-to-face interviews were conducted for the NCS-R in a national sample of 9,282 people, of whom 5,692 were assessed for a history of cancer. Participants with cancer diagnoses at least 5 years before the interview were considered LCSs. Survivors of childhood cancers were excluded. Comparing LCSs to those without a cancer history, odds ratios for having a MDD episode in the last 12 months before interview were obtained using multiple logistic regression controlling for demographic and medical variables. Differences in characteristics of those MDD episodes were also compared between groups. Results Of participants age 23 years or older, 243 LCSs and 4,890 adults without a cancer history were identified in the sample. Adjusting for demographic variables and medical comorbidities, LCSs did not have increased odds of MDD in the last 12 months, with an odds ratio of (OR) 0.99 (95% CI, 0.55 to 1.79). LCSs reported higher mean levels of impairment from MDD in their home, social, and work life, but these differences were not significant. Conclusion LCSs do not appear to have elevated rates of MDD. However, they may experience greater impairment from MDD compared to those without cancer. Longitudinal studies are needed to confirm these findings. C1 [Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Support Oncol Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Support Oncol Res Program, Yawkey 9A,55 Fruit St, Boston, MA 02114 USA. EM wpirl@partners.org RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU National Institutes of Health/National Cancer Institute [K23 CA115908] FX Supported by Grant No. K23 CA115908 from the National Institutes of Health/National Cancer Institute (W. F. P.). NR 22 TC 18 Z9 18 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2009 VL 27 IS 25 BP 4130 EP 4134 DI 10.1200/JCO.2008.16.2784 PG 5 WC Oncology SC Oncology GA 488WN UT WOS:000269381100017 PM 19636024 ER PT J AU Abel, GA Burstein, HJ Hevelone, ND Weeks, JC AF Abel, Gregory A. Burstein, Harold J. Hevelone, Nathanael D. Weeks, Jane C. TI Cancer-Related Direct-to-Consumer Advertising: Awareness, Perceptions, and Reported Impact Among Patients Undergoing Active Cancer Treatment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHYSICIAN; ATTITUDES; BEHAVIOR; ONCOLOGY; CARE; ADS AB Purpose Although cancer-related direct-to-consumer advertising (CR-DTCA) is prevalent, little is known about cancer patients' experiences with this controversial medium of medical communication. Methods We administered a 41-item, mailed questionnaire to consecutive patients with breast and hematologic malignancies who were undergoing active treatment at our institution. We assessed awareness of CR-DTCA within the prior year, perceptions of CR-DTCA, and CR-DTCA-prompted patient and provider behaviors. Results We received 348 completed questionnaires (response rate, 75.0%). Overall, 86.2% reported being aware of CR-DTCA, most frequently from television (77.7%). Awareness did not vary with clinical or sociodemographic factors except that patients were more likely to be aware of CR-DTCA for products specific to their cancer types (P < .0001). A majority of those aware reported that CR-DTCA made them "aware of treatments they did not know about" (62.2%), provided information in "a balanced manner" (65.2%), and helped them to have "better discussions" with their provider (56.8%). These perceptions were significantly more favorable among those who had not graduated from college (P < .05 for each). Overall, 11.2% reported that CR-DTCA made them "less confident" in their providers' judgment. Of those aware, 17.3% reported talking to their provider about an advertised medication, although less than one fifth of those reported receiving a prescription for the advertised medication. Conclusion The patients in our cohort were highly aware of CR-DTCA. CR-DTCA was found to be accessible and useful; however, it decreased some patients' confidence in their providers' judgment. CR-DTCA prompted a modest amount of patient-provider discussion but infrequent patient-reported changes in therapy. C1 [Abel, Gregory A.] Harvard Univ, Ctr Outcomes & Policy Res, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Div Womens Canc, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Abel, GA (reprint author), Harvard Univ, Ctr Outcomes & Policy Res, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, 44 Binney St,Smith 271, Boston, MA 02115 USA. EM gregory_abel@dfci.harvard.edu OI Hevelone, Nathanael/0000-0003-4740-2085 FU American Society of Clinical Oncology Cancer Foundation FX Supported by a Young Investigator Award from the American Society of Clinical Oncology Cancer Foundation. NR 26 TC 17 Z9 17 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2009 VL 27 IS 25 BP 4182 EP 4187 DI 10.1200/JCO.2008.20.6599 PG 6 WC Oncology SC Oncology GA 488WN UT WOS:000269381100025 PM 19652071 ER PT J AU Demetri, GD Chawla, SP von Mehren, M Ritch, P Baker, LH Blay, JY Hande, KR Keohan, ML Samuels, BL Schuetze, S Lebedinsky, C Elsayed, YA Izquierdo, MA Gomez, J Park, YC Le Cesne, A AF Demetri, George D. Chawla, Sant P. von Mehren, Margaret Ritch, Paul Baker, Laurence H. Blay, Jean Y. Hande, Kenneth R. Keohan, Mary L. Samuels, Brian L. Schuetze, Scott Lebedinsky, Claudia Elsayed, Yusri A. Izquierdo, Miguel A. Gomez, Javier Park, Youn C. Le Cesne, Axel TI Efficacy and Safety of Trabectedin in Patients With Advanced or Metastatic Liposarcoma or Leiomyosarcoma After Failure of Prior Anthracyclines and Ifosfamide: Results of a Randomized Phase II Study of Two Different Schedules SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID SOFT-TISSUE SARCOMAS; HIGH-DOSE IFOSFAMIDE; EUROPEAN ORGANIZATION; 2ND-LINE CHEMOTHERAPY; ANTICANCER AGENTS; OVARIAN-CANCER; ADULT PATIENTS; END-POINT; TRIAL; EPIRUBICIN AB Purpose To evaluate the safety and efficacy of trabectedin in a phase II, open-label, multicenter, randomized study in adult patients with unresectable/metastatic liposarcoma or leiomyosarcoma after failure of prior conventional chemotherapy including anthracyclines and ifosfamide. Patients and Methods Patients were randomly assigned to one of two trabectedin regimens (via central venous access): 1.5 mg/m(2) 24-hour intravenous infusion once every 3 weeks (q3 weeks 24-hour) versus 0.58 mg/m(2) 3-hour IV infusion every week for 3 weeks of a 4-week cycle (qwk 3- hour). Time to progression (TTP) was the primary efficacy end point, based on confirmed independent review of images. Results Two hundred seventy patients were randomly assigned; 136 (q3 weeks 24-hour) versus 134 (qwk 3-hour). Median TTP was 3.7 months versus 2.3 months (hazard ratio [HR], 0.734; 95% CI, 0.554 to 0.974; P = .0302), favoring the q3 weeks 24-hour arm. Median progression-free survival was 3.3 months versus 2.3 months (HR, 0.755; 95% CI, 0.574 to 0.992; P = .0418). Median overall survival (n = 235 events) was 13.9 months versus 11.8 months (HR, 0.843; 95% CI, 0.653 to 1.090; P = .1920). Although somewhat more neutropenia, elevations in AST/ALT, emesis, and fatigue occurred in the q3 weeks 24-hour, this regimen was reasonably well tolerated. Febrile neutropenia was rare (0.8%). No cumulative toxicities were noted. Conclusion Prior studies showed clinical benefit with trabectedin in patients with sarcomas after failure of standard chemotherapy. This trial documents superior disease control with the q3 weeks 24-hour trabectedin regimen in liposarcomas and leiomyosarcomas, although the qwk 3- hour regimen also demonstrated activity relative to historical comparisons. Trabectedin may now be considered an important new option to control advanced sarcomas in patients after failure of available standard-of-care therapies. C1 Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Sarcoma Oncol Ctr, Santa Monica, CA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. N Idaho Canc Ctr, Coeur Dalene, ID USA. Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. Ctr Leon Berard, F-69373 Lyon, France. PharmaMar Clin R&D, Madrid, Spain. Inst Gustave Roussy, Villejuif, France. RP Demetri, GD (reprint author), Ctr Sarcoma & Bone Oncol, D1212,44 Binney St, Boston, MA 02115 USA. EM gdemetri@partners.org RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 33 TC 236 Z9 244 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2009 VL 27 IS 25 BP 4188 EP 4196 DI 10.1200/JCO.2008.21.0088 PG 9 WC Oncology SC Oncology GA 488WN UT WOS:000269381100026 PM 19652065 ER PT J AU Veazey, C Cook, KF Stanley, M Lai, EC Kunik, ME AF Veazey, Connie Cook, Karon F. Stanley, Melinda Lai, Eugene C. Kunik, Mark E. TI Telephone-Administered Cognitive Behavioral Therapy: A Case Study of Anxiety and Depression in Parkinson's Disease SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE Cognitive behavioral therapy; Parkinson's disease; Anxiety; Depression; Chronic illness ID OBSTRUCTIVE PULMONARY-DISEASE; ELDERLY-PATIENTS; PRIMARY-CARE; MULTIPLE-SCLEROSIS; SCREENING TOOL; DISORDERS; PREVALENCE; VALIDATION; SYMPTOMS; QUESTIONNAIRE AB Parkinson's disease (PD) is a chronic medical illness with a high incidence of psychiatric comorbidity, specifically depression and anxiety. Research on treatment of such psychiatric complications is scarce. Non-pharmaceutical treatment options are especially attractive. Cognitive behavioral therapy (CBT) is a psychotherapeutic treatment option that has been successful in other chronically medically ill populations with comorbid depression and anxiety. The current research had two aims. The first was to pilot the feasibility of screening and identifying PD patients with symptoms of anxiety and depression in a specialized outpatient clinic. The second aim was to pilot the feasibility of telephone-administered CBT for the treatment of depression and anxiety in persons with PD, which was done through a case series comparing telephone-administered CBT to a Support strategy. A fairly large portion (67.5%) of patients screened in the outpatient clinic were identified as having symptoms of anxiety and/or depression. Results also indicated that CBT delivered via the telephone is a useful approach for targeting psychiatric symptoms in this population. A case example is given to illustrate the clinical considerations associated with delivering therapy via telephone to persons with PD. C1 [Veazey, Connie] Univ Louisiana Lafayette, Dept Psychol, Lafayette, LA 70504 USA. [Cook, Karon F.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Stanley, Melinda; Kunik, Mark E.] Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX USA. [Stanley, Melinda; Lai, Eugene C.; Kunik, Mark E.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Stanley, Melinda; Kunik, Mark E.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Stanley, Melinda; Kunik, Mark E.] Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX USA. [Lai, Eugene C.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Lai, Eugene C.] Houston VA Parkinsons Dis Res Educ & Clin Ctr, Houston, TX USA. [Kunik, Mark E.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Veazey, C (reprint author), Univ Louisiana Lafayette, Dept Psychol, POB 43131, Lafayette, LA 70504 USA. EM veazey@louisiana.edu NR 49 TC 22 Z9 22 U1 3 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD SEP PY 2009 VL 16 IS 3 BP 243 EP 253 DI 10.1007/s10880-009-9167-6 PG 11 WC Psychology, Clinical SC Psychology GA 473FL UT WOS:000268191400005 PM 19404724 ER PT J AU Chua, EF Schacter, DL Sperling, RA AF Chua, Elizabeth F. Schacter, Daniel L. Sperling, Reisa A. TI Neural Correlates of Metamemory: A Comparison of Feeling-of-Knowing and Retrospective Confidence Judgments SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID EVENT-RELATED FMRI; RECOGNITION MEMORY; PREFRONTAL CORTEX; CUE-FAMILIARITY; BASE-LINE; RETRIEVAL; ACCURACY; BRAIN; METACOGNITION; THOUGHT AB Metamemory refers to knowledge and monitoring of one's own memory. Metamemory monitoring can be done prospectively with respect to subsequent memory retrieval or retrospectively with respect to previous memory retrieval. In this study, we used fMRI to compare neural activity during prospective feeling-of-knowing and retrospective confidence tasks in order to examine common and distinct mechanisms supporting multiple forms of metamemory monitoring. Both metamemory tasks, compared to non-metamemory tasks, were associated with greater activity in medial prefrontal, medial parietal, and lateral parietal regions, which have previously been implicated in internally directed cognition. Furthermore, compared to non-metamemory tasks, metamemory tasks were associated with less activity in occipital regions, and in lateral inferior frontal and dorsal medial prefrontal regions, which have previously shown involvement in visual processing and stimulus-oriented attention, respectively. Thus, neural activity related to metamemory is characterized by both a shift toward internally directed cognition and away from externally directed cognition. Several regions demonstrated differences in neural activity between feeling-of-knowing and confidence tasks, including fusiform, medial temporal lobe, and medial parietal regions; furthermore, these regions also showed interaction effects between task and the subjective metamemory rating, suggesting that they are sensitive to the information monitored in each particular task. These findings demonstrate both common and distinct neural mechanisms supporting metamemory processes and also serve to elucidate the functional roles of previously characterized brain networks. C1 [Chua, Elizabeth F.; Sperling, Reisa A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chua, Elizabeth F.; Schacter, Daniel L.] Harvard Univ, Cambridge, MA 02138 USA. [Chua, Elizabeth F.; Schacter, Daniel L.; Sperling, Reisa A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chua, EF (reprint author), Harvard Psychol, William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM echua@nmr.mgh.harvard.edu RI Chua, Elizabeth/B-3770-2010; OI Schacter, Daniel/0000-0002-2460-6061 FU NINDS [K23-NS02189]; NIA [P01-AG-04953, R01AG027435]; AFAR Beeson Scholars in Aging Program; NIMH [MH60941]; National Science Foundation Graduate Research Fellowship; NCRR [P41RR14075]; MIND Institute; Athinoula A. Martinos Center for Biomedical Imaging; Harvard Center for NeuroDiscovery FX We thank Kristina Depeau, Kim Celone, and Saul Miller for help with data acquisition. This work was supported by NINDS: K23-NS02189 (R. S.); NIA: P01-AG-04953 (R. S.) and R01AG027435 (R. S.); the AFAR Beeson Scholars in Aging Program (R. S.); NIMH: MH60941 (D. S.); a National Science Foundation Graduate Research Fellowship (E. C.); NCRR: P41RR14075; the MIND Institute; the Athinoula A. Martinos Center for Biomedical Imaging; and the Harvard Center for NeuroDiscovery. NR 41 TC 52 Z9 56 U1 1 U2 18 PU M I T PRESS PI CAMBRIDGE PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SEP PY 2009 VL 21 IS 9 BP 1751 EP 1765 DI 10.1162/jocn.2009.21123 PG 15 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 505ZE UT WOS:000270740200009 PM 18823230 ER PT J AU Sun, D Lye-Barthel, M Masland, RH Jakobs, TC AF Sun, Daniel Lye-Barthel, Ming Masland, Richard H. Jakobs, Tatjana C. TI The Morphology and Spatial Arrangement of Astrocytes in the Optic Nerve Head of the Mouse SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE glial lamina; optic nerve; white matter astrocytes; GFP; glaucoma; ganglion cell axons ID GANGLION-CELL DEGENERATION; TRANSGENIC MICE; LAMINA-CRIBROSA; WHITE-MATTER; IN-VITRO; PROTOPLASMIC ASTROCYTES; QUANTITATIVE-ANALYSIS; GLIAL FRAMEWORK; FREEZE-FRACTURE; DBA/2J MICE AB We evaluated the shapes, numbers, and spatial distribution of astrocytes within the glial lamina, an astrocyte-rich region at the junction of the retina and optic nerve. A primary aim was to determine how the population of astrocytes, collectively, partitions the axonal space in this region. Astrocyte processes labeled with glial fibrillary acidic protein (GFAP) compartmentalize ganglion cell axons into bundles, forming "glial tubes," and giving the glial architecture of the optic nerve head in transverse section a honeycomb appearance. The shapes of individual astrocytes were studied by using transgenic mice that express enhanced green fluorescent protein in isolated astrocytes (hGFAPpr-EGFP). Within the glial lamina the astrocytes were transverse in orientation, with thick, smooth primary processes emanating from a cytoplasmic expansion of the soma. Spaces between the processes of neighboring astrocytes were spatially aligned, to form the apertures through which the bundles of optic axons pass. The processes of individual astrocytes were far-reaching-they could span most of the width of the nerve-and overlapped the anatomical domains of other near and distant astrocytes. Thus, astrocytes in the glial lamina do not tile: each astrocyte participates in ensheathing approximately one-quarter of all of the axon bundles in the nerve, and each glial tube contains the processes of about nine astrocytes. This raises the mechanistic question of how, in glaucoma or other cases of nerve damage, the glial response can be confined to a circumscribed region where damage to axons has occurred. J. Comp. Neurol. 516:1-19, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Sun, Daniel; Lye-Barthel, Ming; Masland, Richard H.; Jakobs, Tatjana C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Jakobs, TC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Thier 429,50 Blossom St, Boston, MA 02114 USA. EM Jakobs@helix.mgh.harvard.edu OI Jakobs, Tatjana/0000-0002-8104-9206 FU National Institutes of Health [R01-EY017169] FX Grant sponsor: National Institutes of Health; Grant number: R01-EY017169. NR 90 TC 56 Z9 59 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 1 PY 2009 VL 516 IS 1 BP 1 EP 19 DI 10.1002/cne.22058 PG 19 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 472HD UT WOS:000268120300001 PM 19562764 ER PT J AU Berthiaume, LR Peets, AD Schmidt, U Shahpori, R Doig, CJ Boiteau, PJE Stelfox, HT AF Berthiaume, Luc R. Peets, Adam D. Schmidt, Ulrich Shahpori, Reza Doig, Chip J. Boiteau, Paul J. E. Stelfox, Henry Thomas TI Time series analysis of use patterns for common invasive technologies in critically ill patients SO JOURNAL OF CRITICAL CARE LA English DT Article DE Critical care medicine; Technology; Patient safety; Medical education ID PULMONARY-ARTERY CATHETER; RANDOMIZED CONTROLLED-TRIAL; SEPSIS CAMPAIGN GUIDELINES; INTENSIVE-CARE-UNIT; SEPTIC SHOCK; MANAGEMENT; PHYSICIANS; KNOWLEDGE; OUTCOMES; DIFFUSION AB Purpose: Critically ill patients are frequently managed with invasive technologies as part of their medical care. Little is known about use patterns. We examined use trends for invasive technologies used in critically ill patients. Materials and Methods: Using time series analysis and data on 26 989 patients from 3 medical-surgical intensive care units (ICUs) (n = 18 224) and 1 surgical ICU (n = 8765) between January 1, 1999, and January 1, 2007, we measured changes in the proportion of patients receiving the 4 most frequently used invasive technologies used in critically ill patients. Results: The 4 most common invasive technologies used in critically ill patients during the study period were arterial lines (71%), endotracheal intubations (61%), central venous catheters (51%), and pulmonary artery catheters (18%). The proportion of ICU patients who received pulmonary artery catheters decreased from 25% in 1999 to 8% in 2006 (P < .001). Use of central venous catheters increased from 39% to 46% (P < .001). After adjusting for baseline characteristics, patients admitted in 2006 were 4 times less likely to receive a pulmonary artery catheter (odds ratio, 0.28; 95% confidence interval, 0.24-0.33), but 42% (odds ratio, 1.42; 95% confidence interval, 1.27-1.58) more likely to receive a central venous catheter than patients admitted in 1999. No significant changes were observed for intubations and arterial lines. Conclusions: The use of invasive technologies in critically ill patients is changing and may have important implications for resource use, clinician education, and patient care. Initiatives should be considered for ensuring clinician competency during technology transitions. (C) 2009 Elsevier Inc. All rights reserved. C1 [Berthiaume, Luc R.; Peets, Adam D.; Shahpori, Reza; Doig, Chip J.; Boiteau, Paul J. E.; Stelfox, Henry Thomas] Univ Calgary, Foothills Med Ctr, Dept Crit Care Med, Calgary, AB T2N 2T9, Canada. [Schmidt, Ulrich] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Stelfox, HT (reprint author), Univ Calgary, Foothills Med Ctr, Dept Crit Care Med, Calgary, AB T2N 2T9, Canada. EM tom.stelfox@calgaryhealthregion.ca NR 25 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 J9 J CRIT CARE JI J. Crit. Care PD SEP PY 2009 VL 24 IS 3 AR 471.e9 DI 10.1016/j.jcrc.2008.07.004 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 674EK UT WOS:000283716800013 PM 19327306 ER PT J AU Nagano, T Kakegawa, A Yamakoshi, Y Tsuchiya, S Hu, JCC Gomi, K Arai, T Bartlett, JD Simmer, JP AF Nagano, T. Kakegawa, A. Yamakoshi, Y. Tsuchiya, S. Hu, J. C. -C. Gomi, K. Arai, T. Bartlett, J. D. Simmer, J. P. TI Mmp-20 and Klk4 Cleavage Site Preferences for Amelogenin Sequences SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE TRAP; LRAP; enamel; tooth; fluorescent peptides ID DEVELOPING DENTAL ENAMEL; MESSENGER-RNA; MATRIX METALLOPROTEINASE-20; PORCINE AMELOGENIN; IMPERFECTA; CLONING; TOOTH; HYDROLYSIS; EXPRESSION; BOVINE AB Mmp-20 and Klk4 are the two key enamel proteases. Can both enzymes process amelogenin to generate the major cleavage products that accumulate during the secretory stage of amelogenesis? We isolated Mmp-20 and Klk4 from developing pig teeth and used them to digest the tyrosine-rich amelogenin polypeptide (TRAP), the leucine-rich amelogenin protein (LRAP), and 5 fluorescence peptides. We characterized the digestion products by LC-MSMS, SDS-PAGE, and C18 RP-HPLC monitored with fluorescence and UV detectors. Mmp-20 cleaves amelogenin sequences after Pro(162), Ser(148), His(62), Ala(63), and Trp(45). These cleavages generate all of the major cleavage products that accumulate in porcine secretory-stage enamel: the 23-kDa, 20-kDa, 13-kDa, 11-kDa, and 6-kDa (TRAP) amelogenins. Mmp-20 cleaves LRAP after Pro(45) and Pro(40), producing the two LRAP products previously identified in tooth extracts. Among these key cleavage sites, Klk4 was able to cleave only after His(62). We propose that Mmp-20 alone processes amelogenin during the secretory stage. C1 [Nagano, T.; Yamakoshi, Y.; Tsuchiya, S.; Hu, J. C. -C.; Simmer, J. P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Nagano, T.; Kakegawa, A.; Gomi, K.; Arai, T.] Tsurumi Univ, Dept Periodont & Endodont, Sch Dent Med, Tsurumi Ku, Yokohama, Kanagawa 2308501, Japan. [Bartlett, J. D.] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. RP Simmer, JP (reprint author), Univ Michigan, Dent Res Lab, 1210 Eisenhower Pl, Ann Arbor, MI 48108 USA. EM jsimmer@umich.edu FU NIDCR/NIH [DE015846, DE016276] FX We thank the Michigan State University Meat Laboratory for fresh developing molars. This investigation was supported by USPHS Research Grants DE015846 and DE016276 from the NIDCR/NIH. All authors declare that there are no conflicting interests. NR 35 TC 47 Z9 48 U1 3 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 2009 VL 88 IS 9 BP 823 EP 828 DI 10.1177/0022034509342694 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 499CL UT WOS:000270194100007 PM 19767579 ER PT J AU Barnes, VM Teles, R Trivedi, HM Devizio, W Xu, T Mitchell, MW Milburn, MV Guo, L AF Barnes, V. M. Teles, R. Trivedi, H. M. Devizio, W. Xu, T. Mitchell, M. W. Milburn, M. V. Guo, L. TI Acceleration of Purine Degradation by Periodontal Diseases SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE metabolomics; periodontitis; reactive oxygen species; biomarkers ID GINGIVAL CREVICULAR FLUID; XANTHINE-OXIDASE; REACTIVE OXYGEN; HEALTH; SERUM AB Periodontal diseases, such as gingivitis and periodontitis, are characterized by bacterial plaque accumulation around the gingival crevice and the subsequent inflammation and destruction of host tissues. To test the hypothesis that cellular metabolism is altered as a result of host-bacteria interaction, we performed an unbiased metabolomic profiling of gingival crevicular fluid (GCF) collected from healthy, gingivitis, and periodontitis sites in humans, by liquid and gas chromatography mass spectrometry. The purine degradation pathway, a major biochemical source for reactive oxygen species (ROS) production, was significantly accelerated at the disease sites. This suggests that periodontal-disease-induced oxidative stress and inflammation are mediated through this pathway. The complex host-bacterial interaction was further highlighted by depletion of anti-oxidants, degradation of host cellular components, and accumulation of bacterial products in GCF. These findings provide new mechanistic insights and a panel of comprehensive biomarkers for periodontal disease progression. C1 [Mitchell, M. W.; Milburn, M. V.; Guo, L.] Metabolon Inc, Durham, NC 27713 USA. [Barnes, V. M.; Trivedi, H. M.; Devizio, W.; Xu, T.] Colgate Palmol Technol Ctr, Piscataway, NJ 08855 USA. [Teles, R.] Forsyth Inst, Boston, MA 02115 USA. RP Guo, L (reprint author), Metabolon Inc, 800 Capitola Dr,Suite 1, Durham, NC 27713 USA. EM lguo@metabolon.com OI Mitchell, Matthew/0000-0002-2681-4091 FU Colgate-Palmolive Company FX The authors thank Drs. Danny Alexander, Kirk Beebe, and Allen Phillips for helpful discussions. This investigation was supported by a research grant from Colgate-Palmolive Company to The Forsyth Institute and Metabolon Inc. Virginia Barnes, Harsh Trivedi, William Devizio, and Tao Xu are employees of ColgatePalmolive Company. Ricardo Teles is an employee of The Forsyth Institute. Matthew Mitchell, Michael Milburn, and Lining Guo are employees of Metabolon. NR 23 TC 32 Z9 33 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 2009 VL 88 IS 9 BP 851 EP 855 DI 10.1177/0022034509341967 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 499CL UT WOS:000270194100012 PM 19767584 ER PT J AU Hahn, JO Reisner, AT Asada, HH AF Hahn, Jin-Oh Reisner, Andrew T. Asada, H. Harry TI Blind Identification of Two-Channel IIR Systems With Application to Central Cardiovascular Monitoring SO JOURNAL OF DYNAMIC SYSTEMS MEASUREMENT AND CONTROL-TRANSACTIONS OF THE ASME LA English DT Article DE blood vessels; cardiovascular system; medical signal processing; signal reconstruction; wave propagation ID CARDIAC-OUTPUT; PRESSURE WAVE; NONINVASIVE ESTIMATION; MODEL; DERIVATION; SIGNALS; FORM AB This paper presents a new approach to blind identification of a class of two-channel infinite impulse response (IIR) systems with applicability to clinical cardiovascular monitoring. Specifically, this paper deals with a class of two-channel IIR systems describing wave propagation dynamics. For this class of systems, this paper first derives a blind identifiability condition and develops a blind identification algorithm, which is able to determine both the numerator and denominator polynomials of the channel dynamics uniquely. This paper also develops a new input signal deconvolution algorithm that can reconstruct the input signal from the identified two-channel dynamics and the associated two-channel measurements. These methods are applied to identify the pressure wave propagation dynamics in the cardiovascular system and reconstruct the aortic blood pressure and flow signals from blood pressure measurements taken at two distinct extremity locations. Persistent excitation, model identifiability, and asymptotic variance are analyzed to quantify the method's validity, accuracy, and reliability without employing direct measurement of the aortic blood pressure and flow signals. The experimental results based on 83 data segments obtained from a swine subject illustrate how the cardiovascular dynamics can be identified accurately and reliably, and the aortic blood pressure and flow signals can be stably reconstructed from two distinct peripheral blood pressure signals under diverse physiologic conditions. C1 [Hahn, Jin-Oh; Asada, H. Harry] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Hahn, JO (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM jinoh.hahn@alum.mit.edu; areisner@partners.org; asada@mit.edu OI Hahn, Jin-Oh/0000-0001-5429-2836 FU Sharp Corporation FX This work was supported in part by the Sharp Corporation. NR 29 TC 8 Z9 8 U1 0 U2 7 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0022-0434 J9 J DYN SYST-T ASME JI J. Dyn. Syst. Meas. Control-Trans. ASME PD SEP PY 2009 VL 131 IS 5 AR 051009 DI 10.1115/1.3155011 PG 15 WC Automation & Control Systems; Instruments & Instrumentation SC Automation & Control Systems; Instruments & Instrumentation GA 485NZ UT WOS:000269131600009 ER PT J AU Glezer, A Murray, E Price, B Cunningham, M AF Glezer, Anna Murray, Evan Price, Bruce Cunningham, Miles TI Effective Use of Electroconvulsive Therapy After Craniofacial Reconstructive Surgery SO JOURNAL OF ECT LA English DT Article DE major depressive disorder; ECT; metallic implant; craniofacial surgery ID ECT AB The present case report describes a 53-year-old male patient with long-standing, refractory major depressive disorder admitted for electroconvulsive therapy. The patient had a history of head trauma and was status-post craniofacial surgery with mesh and metallic implants. We describe the patient's history and the concerns associated with performing electroconvulsive therapy on a patient with metallic skull implants, and we conclude with an account of successful treatment. C1 [Cunningham, Miles] Harvard Univ, Sch Med, McLean Hosp, Lab Neural Reconstruct, Belmont, MA 02478 USA. [Glezer, Anna] McLean Hosp, Massachusetts Gen Hosp, Psychiat Residency Training Program, Boston, MA USA. [Murray, Evan; Price, Bruce] Harvard Univ, Sch Med, McLean Hosp, Dept Behav Neurol, Belmont, MA 02478 USA. RP Cunningham, M (reprint author), Harvard Univ, Sch Med, McLean Hosp, Lab Neural Reconstruct, MRC 312,115 Mill St, Belmont, MA 02478 USA. EM mcunningham@mclean.harvard.edu NR 7 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD SEP PY 2009 VL 25 IS 3 BP 208 EP 209 PG 2 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 493BQ UT WOS:000269708500014 PM 19145209 ER PT J AU Casamassima, F Lattanzi, L Perlis, RH Fratta, S Litta, A Longobardi, A Stange, JP Tatulli, A Cassano, GB AF Casamassima, Francesco Lattanzi, Lorenzo Perlis, Roy H. Fratta, Sara Litta, Antonella Longobardi, Antonio Stange, Jonathan P. Tatulli, Alessandro Cassano, Giovanni B. TI Efficacy of Electroconvulsive Therapy in Fahr Disease Associated With Bipolar Psychotic Disorder A Case Report SO JOURNAL OF ECT LA English DT Article DE Fahr disease; bipolar disorder; electroconvulsive therapy ID BASAL GANGLIA CALCIFICATION; NEUROPSYCHIATRY; DEPRESSION; CIRCUITS; LOCUS; ECT AB We report a case of a patient with Fahr disease affected by bipolar disorder type I with psychotic symptoms. The complex clinical picture, characterized by both neurological and psychiatric symptoms, proved to be partially or completely resistant to several pharmacological trials. On the contrary, a marked improvement of clinical picture occurred after a cycle of 10 sessions of electroconvulsive therapy, followed by a complete and sustained resolution of mood, cognitive, motor, and behavioral symptoms during the next 4 years. C1 [Casamassima, Francesco] Univ Pisa, Dipartimento Psichiatria, Div Psychiat, I-56100 Pisa, Italy. [Casamassima, Francesco; Perlis, Roy H.; Stange, Jonathan P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Perlis, Roy H.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Casamassima, F (reprint author), Univ Pisa, Dipartimento Psichiatria, Div Psychiat, Via Roma 67, I-56100 Pisa, Italy. EM fcasamassima@partners.org NR 22 TC 3 Z9 3 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD SEP PY 2009 VL 25 IS 3 BP 213 EP 215 PG 3 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 493BQ UT WOS:000269708500016 PM 19252444 ER PT J AU AlShwaimi, E Purcell, P Kawai, T Sasaki, H Oukka, M Campos-Neto, A Stashenko, P AF AlShwaimi, Emad Purcell, Patricia Kawai, Toshihisa Sasaki, Hajime Oukka, Mohamed Campos-Neto, Antonio Stashenko, Philip TI Regulatory T Cells in Mouse Periapical Lesions SO JOURNAL OF ENDODONTICS LA English DT Article DE Flow cytometry; FOXP3/GFP knock-in; in situ hybridization; periapical lesions; pulp infection; T-regulatory cells ID TRANSCRIPTION FACTOR FOXP3; PLASMA-CELLS; BONE-MARROW; RAT MOLARS; DISEASE; INTERLEUKIN-2; HYBRIDIZATION; MACROPHAGES; IMMUNITY; LINEAGE AB Introduction: T-regulatory (Treg, CD4+ FOXP3+) cells constitute a unique subpopulation of CD4+ T cells that inhibit T-cell responses and prevent disease development/exacerbation in models of autoimmunity. In the present study, we tested the hypothesis that Treg cells are induced in periapical lesions by dental pulp infection. Methods: In situ hybridization (ISH) was used to localize FOXP3+ cells on day 21 after pulp exposure of the first molar teeth and infection with bacteria from the oral environment. FOXP3/GFP knock-in transgenic mice were used to quantify FOXP3+ Treg cells that infiltrate into periapical lesions by flow cytometry on days 7, 14, and 21 after infection. Periodontal ligament from uninfected teeth served as a negative control. Results: ISH showed strong signals that showed the presence of FOXP3+ cells mainly at the periphery of periapical lesions. In contrast, no positive cells were present in the periodontal ligament of uninfected controls. Flow cytometry showed an increase in the number of FOXP3+ Treg beginning between day 7 and day 14 (0.69% of the infiltrate) after infection and increased to day 21 (0.94%) (p < 0.05 and p < 0.001, respectively, vs uninfected controls). Treg were also increased in number in draining cervical lymph nodes after pulpal infection. Conclusions:These results show that Treg cells are induced to infiltrate into periapical lesions by pulpal infection and suggest that they increase in a time-dependent manner. (J Endod 2009;35:1229-1233) C1 [Sasaki, Hajime; Campos-Neto, Antonio; Stashenko, Philip] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. [Oukka, Mohamed] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Purcell, Patricia] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [AlShwaimi, Emad] King Faisal Univ, Coll Dent, Dept Restorat Dent, Dammam, Saudi Arabia. [AlShwaimi, Emad] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, Boston, MA 02115 USA. RP Stashenko, P (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM pstashenko@forsyth.org RI AlShwaimi, Emad /F-4077-2012 FU AAE Foundation; Krakow Endodontic Research Fund [R01 DE-09018, K22 DE-16309, DE-18499]; NIDCR/NIH FX We thank Dr. Xiazohe Han for flow cytometry analysis, Ms. Justine Dobeck for histology and Mr. Subbiah Yoganathan for animal care. This work was supported by grants from the AAE Foundation (E.A), the Krakow Endodontic Research Fund (EA), R01 DE-09018 (P.S.), K22 DE-16309 (P.P), and DE-18499 (T.K) from the NIDCR/NIH. "NO FINANCIAL AFFILIATION EXISTS FOR ALL AUTHORS." NR 30 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD SEP PY 2009 VL 35 IS 9 BP 1229 EP 1233 DI 10.1016/j.joen.2009.06.006 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 493TJ UT WOS:000269760600011 PM 19720221 ER PT J AU Ramanujam, CL Lakhani, S Derk, F Fulton, R Zgonis, T AF Ramanujam, Crystal L. Lakhani, Shirmeen Derk, Francis Fulton, Rebecca Zgonis, Thomas TI Cutaneous Non-Hodgkin's Lymphoma of the Foot: A Rare Case Report SO JOURNAL OF FOOT & ANKLE SURGERY LA English DT Article DE biopsy; lymphocyte; Mohs; neoplasm; oncology; tumor ID B-CELL LYMPHOMA; CLASSIFICATION; ORGANIZATION; PERSPECTIVE AB Lymphomas comprise a heterogeneous group of cancers originating in cells of the immune system at different stages of differentiation. Primary cutaneous non-Hodgkin lymphoma of the foot is a rare occurrence. We present a case involving a primary cutaneous marginal zone lymphoma of the foot, and highlight the clinical recognition and treatment of this condition. Level of Clinical Evidence: 4 (The Journal of Foot & Ankle Surgery 48(5):581-584, 2009) C1 [Ramanujam, Crystal L.; Lakhani, Shirmeen; Zgonis, Thomas] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthopaed, Div Podiatr Med & Surg, San Antonio, TX 78229 USA. [Derk, Francis] Audie L Murphy Mem Vet Adm Med Ctr, Dept Surg, San Antonio, TX USA. [Fulton, Rebecca] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Zgonis, Thomas] Univ Texas Hlth Sci Ctr San Antonio, Podiatr Surg Residency Program, San Antonio, TX 78229 USA. [Zgonis, Thomas] Univ Texas Hlth Sci Ctr San Antonio, Reconstruct Foot & Ankle Fellowship Program, San Antonio, TX 78229 USA. RP Zgonis, T (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Orthopaed, Div Podiatr Med & Surg, 7703 Floyd Curl Dr,MC 7776, San Antonio, TX 78229 USA. EM zgonis@uthscsa.edu NR 14 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-2516 J9 J FOOT ANKLE SURG JI J. Foot Ankle Surg. PD SEP-OCT PY 2009 VL 48 IS 5 BP 581 EP 584 DI 10.1053/j.jfas.2009.05.002 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 494NL UT WOS:000269820100012 PM 19700123 ER PT J AU Park, ER Chun, MBJ Betancourt, JR Green, AR Weissman, JS AF Park, Elyse R. Chun, Maria B. J. Betancourt, Joseph R. Green, Alexander R. Weissman, Joel S. TI Measuring Residents' Perceived Preparedness and Skillfulness to Deliver Cross-cultural Care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE cultural competency; measurement; medical education-graduate ID SELF-ASSESSMENT; SKILLS AB BACKGROUND: As patient populations become increasingly diverse, we need to be able to measure residents' preparedness and skillfulness to provide cross-cultural care. OBJECTIVE: To develop a measure that assesses residents' perceived readiness and abilities to provide cross-cultural care. DESIGN: Survey items were developed based on an extensive literature review, interviews with experts, and seven focus groups and ten individual interviews, as part of a larger national mailed survey effort of graduating residents in seven specialties. Reliability and weighted principal components analyses were performed with items that assessed perceived preparedness and skillfulness to provide cross-cultural care. Construct validity was assessed. PARTICIPANTS: A total of 2,047 of 3,435 eligible residents participated (response rate=60%). MEASUREMENTS AND MAIN RESULTS: The final scale consisted of 18 items and 3 components (general cross-cultural preparedness, general cross-cultural skillfulness, and cross-cultural language preparedness and skillfulness), and yielded a Cronbach's alpha=0.92. Construct validity was supported; the scale total was inversely correlated with a measure of helplessness when providing care to patients of a different culture (p<0.001). CONCLUSIONS: We developed a three-component cross-cultural preparedness and skillfulness scale that was internally consistent and demonstrated construct validity. This measure can be used to evaluate residents' perceived effectiveness of cross-cultural medical training programs and could be used in future work to validate residents' self assessments with objective assessments. C1 [Park, Elyse R.; Betancourt, Joseph R.; Green, Alexander R.; Weissman, Joel S.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Chun, Maria B. J.] Univ Hawaii, John A Burns Sch Med, Dept Surg, Honolulu, HI 96822 USA. [Weissman, Joel S.] Univ Massachusetts, Sch Med, Dept Family & Community Med, Worcester, MA USA. RP Park, ER (reprint author), 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM epark@partners.org FU The California Endowment [20021803]; The Commonwealth Fund [20020727]; American Cancer Society's Mentored Research Scholar [MRSG-005-05-CPPB] FX Conflict of Interest: Drs. Betancourt and Green have received honoraria from Merck Speakers' Bureau to speak about disparities and cross-cultural care. Dr. Park reports that Pfizer has supplied medication for a pilot smoking cessation trial. Dr. Chun and Dr. Weissman do not have any potential conflicts of interest to report. NR 16 TC 9 Z9 10 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2009 VL 24 IS 9 BP 1053 EP 1056 DI 10.1007/s11606-009-1046-1 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 492UR UT WOS:000269686100011 PM 19557481 ER PT J AU Snyder, KM Ganzini, L AF Snyder, Kristen M. Ganzini, Linda TI Outcomes of Oregon's Law Mandating Physician Reporting of Impaired Drivers SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE driving; elderly; impairment; physician; reporting ID OLDER DRIVERS; VEHICLE CRASHES; ALZHEIMER-TYPE; FATAL CRASHES; DEMENTIA; PERFORMANCE AB Oregon enacted a law in 2002 that requires some health care practitioners to report cognitively impaired drivers to the Department of Motor Vehicles. We examined reports submitted between 2003 and 2006 on 1664 potential impaired drivers. Of reported drivers, 48% were older than 80 years of age. Reports of cognitive impairment were 7 times more common than functional impairments. The most common cognitive impairments were judgment and problem solving (65%), memory (53%), and reaction time (52%). Only 10% of suspended drivers regained their driving privileges. Drivers older than 80 years of age were 6 times less likely to regain privileges compared to drivers 59 years or younger. In summary, Oregon's law resulted in loss of driving privileges in a small number of licensed drivers. Over half were aged 80 years or older, with chronic or progressive cognitive impairments. Further study is needed to determine whether this law reduces crashes and crash-related fatalities. C1 [Snyder, Kristen M.; Ganzini, Linda] Portland VA Med Ctr, Portland, OR USA. [Snyder, Kristen M.; Ganzini, Linda] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Snyder, KM (reprint author), Portland VA Med Ctr P35C, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM snyderk@ohsu.edu FU Department of Veterans Affairs, Health Services Research and Development Research Enhancement Award Program, Portland, Oregon FX This research was supported by the Department of Veterans Affairs, Health Services Research and Development Research Enhancement Award Program, Portland, Oregon. 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. NR 18 TC 5 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2009 VL 22 IS 3 BP 161 EP 165 DI 10.1177/0891988709332943 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 485ZP UT WOS:000269165400002 PM 19307323 ER PT J AU Brouwer, KM Lindenhovius, ALC Ring, D AF Brouwer, Kim M. Lindenhovius, Anneluuk L. C. Ring, David TI Loss of Anterior Translation of the Distal Humeral Articular Surface Is Associated With Decreased Elbow Flexion SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Distal humerus; elbow motion; open reduction internal fixation AB Purpose The normal anterior translation of the articular surface of the distal humerus with respect to the humeral diaphysis facilitates elbow flexion. We hypothesize that there is a correlation between anterior translation of the distal humeral articular surface and flexion after open reduction and internal fixation (ORIF) of a fracture of the distal humerus. Methods Two independent observers evaluated 141 lateral radiographs of patients more than 6 months after fracture of the distal humerus and 155 lateral radiographs of patients without injury of the distal humerus. The distance between the most interior point of the distal humerus articular surface, perpendicular to the humeral shaft, from the anterior border of the distal part of the humeral diaphysis, was measured on lateral radiographs as a percentage of the width of the humeral shaft Results The technique of measuring anterior translation of the distal humeral articular surface had good intra- and interobserver reliability. The most anterior point of the distal humeral articular surface lies an average of 11.7 mm (range, 6.8 to 17.0 mm) in front of the most anterior border of the humeral shaft in normal distal humeri, which represents 62% of the humeral shaft diameter (range, 33% to 91%). There was a limited but significant correlation between flexion and anterior translation as a percentage of the humeral shaft diameter in distal humeri after fracture that was maintained in multivariable statistical models. Conclusions Using a reproducible technique for measuring anterior translation of the distal humerus, there was a correlation between anterior translation of the distal humeral articular surface and elbow flexion after ORIF. Although the weakness of the correlation emphasizes that limitation of elbow flexion after ORIF of a distal humerus fracture is multifactorial, reduced anterior translation of the distal humeral articular surface might be a contributing factor. (J Hand Surg 2009;34A: 1256-1260. (C) 2009 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU AD Foundation FX Support was provided by unrestricted research grants from AD Foundation, Wright Medical, Joint Active Systems, Smith and Nephew, Small Bone Innovations, Biomet, Acumed, Tornier, Marti Keuning Eckhardt Stichting, VSB Fonds, Stichting Wetenschappelijk Onderzoek Orthopaedische (hirurgie, Stichting Professor Michael van Vloten Fonds, and Stichting Anna Fonds. NR 11 TC 1 Z9 1 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2009 VL 34A IS 7 BP 1256 EP 1260 DI 10.1016/j.jhsa.2009.04.013 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 489IU UT WOS:000269414600013 PM 19556074 ER PT J AU Fu, E Li, G Souer, JS Lozano-Calderon, S Herndon, JH Jupiter, JB Chen, NC AF Fu, Eric Li, Guoan Souer, J. Sebastiaan Lozano-Calderon, Santiago Herndon, James H. Jupiter, Jesse B. Chen, Neal C. TI Elbow Position Affects Distal Radioulnar Joint Kinematics SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Elbow; distal radioulnar; kinematics; biomechanics; forearm ID POSTERIOR CRUCIATE LIGAMENT; ULNAR VARIANCE; FOREARM ROTATION; KNEE FLEXION; DISPLACEMENT; TRANSLATION; SUPINATION; PRONATION; WRIST AB Purpose Previous in vivo and in vitro studies of forearm supination-pronation suggest that distal radioulnar joint kinematics may be affected by elbow flexion. The primary hypotheses tested by this study were that, in vivo, ulnar variance changes with elbow flexion and forearm rotation, and the arc of forearm rotation changes in relationship to elbow flexion. Methods Changes in radioulnar kinematics during forearm supination-pronation and elbow flexion (0 degrees to 90 degrees) were studied in 5 uninjured subjects using computed tomography, dual-orthogonal fluoroscopy, and 3-dimensionat modeling. Analysis of variance and post-hoc testing was performed. Results Proximal translation of the radius was greatest with the elbow flexed to 90 degrees with the arm in midpronation. With the arm in midpronation, the translation of the radius was significantly greater at 0 degrees versus 45 degrees of elbow flexion (0.82 +/- 0.59 mm vs 0.65 +/- 0.80 mm, F: 4.49, post hoc: 0.055; p = .05) and significantly smaller at 45 degrees versus 90 degrees of elbow flexion (0.65 +/- 0.80 mm vs 0.97 +/- 0.35 mm, F: 4.49, post hoc: 0.048; p = .05). Proximal translation of the radius in midpronation was significantly greater than when. the forearm was in a supinated position when the elbow was at 0 degrees or 90 degrees flexion (F: 14.90, post hoc: <0.01; p <.01, F: 19.11, post hoc: <0.01, p <.01). The arc of forearm rotation was significantly decreased at 0 degrees compared with 900 of elbow flexion (129.3 degrees +/- 22.2 degrees vs 152.8 degrees +/- 14.4 degrees, F: 3.29, post hoc: 0.79; p = .09). The center of rotation shifted volarly and ulnarly with increasing elbow extension. Conclusions Elbow position affects the kinematics of the distal radioulnar joint. The kinematics of the distal radioulnar joint are primarily affected by forearm rotation and secondarily by elbow flexion. These findings have clinical relevance to our understanding of ulnar impaction, and how elbow position affects the proximal-distal translation of the radius. These findings have implications for the treatment of ulna impaction, radiographic evaluation of the distal ulna, and future biomechanical studies. (J Hand Surg 2009;34A:126.1-1268. (C) 2009 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed, Boston, MA 02114 USA. RP Chen, NC (reprint author), Univ Michigan, 24 Frank Lloyd Wright Dr,POB 0391, Ann Arbor, MI 48106 USA. EM chenneal@med.umich.edu FU American Foundation for Surgery of the Hand/the American Society for Surgery of the Hand; Department of Orthopaedic Surgery at Massachusetts General Hospital; AD Foundation; Smith and Nephew; Wright Medical; Small Bone Innovations, Joint Active Systems; Orthopaedic Trauma Association; National Institutes of Health; Stichting Annafonds, Leiden, The Netherlands; Stichting Michael van Vloten Fonds, Rotterdam, The Netherlands FX Support was received from the American Foundation for Surgery of the Hand/the American Society for Surgery of the Hand (N.C.C., J.H.H., J.B.J., and G.L.). The authors gratefully acknowledge the financial support of the Department of Orthopaedic Surgery at Massachusetts General Hospital. J.B.J. received support from the AD Foundation, Smith and Nephew, Wright Medical, Small Bone Innovations, Joint Active Systems, and the Orthopaedic Trauma Association. G.L. received support from the National Institutes of Health. J.S.S. received support from Stichting Annafonds, Leiden, The Netherlands; and Stichting Michael van Vloten Fonds, Rotterdam, The Netherlands. This study was funded by a basic science grant from the American Foundation for Surgery of the Hand and the American Society for Surgery of the Hand. NR 16 TC 11 Z9 12 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2009 VL 34A IS 7 BP 1261 EP 1268 DI 10.1016/j.jhsa.2009.04.025 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 489IU UT WOS:000269414600014 PM 19576700 ER PT J AU Chang, VW Lauderdale, DS AF Chang, Virginia W. Lauderdale, Diane S. TI Fundamental Cause Theory, Technological Innovation, and Health Disparities: The Case of Cholesterol in the Era of Statins SO JOURNAL OF HEALTH AND SOCIAL BEHAVIOR LA English DT Article; Proceedings Paper CT Annual Meeting of the Population-Association-of-America CY APR 17-19, 2008 CL New Orleans, LA SP Populat Assoc Amer ID MINNESOTA HEART SURVEY; DISEASE RISK-FACTORS; SOCIOECONOMIC-STATUS; CARDIOVASCULAR-DISEASE; UNITED-STATES; US ADULTS; MORTALITY; INEQUALITIES; PATTERNS; TRENDS AB Although fundamental cause theory has been highly influential in shaping the research literature on health disparities, there have been few empirical demonstrations of the theory, particularly in dynamic perspective. In this study, we examine how income disparities in cholesterol levels have changed with the emergence of statins, an expensive and potent new drug technology. Using nationally representative data from 1976 to 2004, we find that income gradients for cholesterol were initially positive, but then reversed and became negative in the era of statin use. While the advantaged were previously more likely to have high levels of cholesterol, they are now less likely. We consider our case study against a broader theoretical framework outlining the relationship between technology innovation and health disparities. We find that the influence of technologies on socioeconomic disparities is subject to two important modifiers: (1) the nature of the technological change and (2) the extent of its diffusion and adoption. C1 [Chang, Virginia W.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Chang, Virginia W.] Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. [Lauderdale, Diane S.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Lauderdale, Diane S.] Univ Chicago, Hlth Studies Coll, Chicago, IL 60637 USA. RP Chang, VW (reprint author), Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. FU NICHD NIH HHS [K12 HD043459, K12 HD043459-05, K12-HD043459] NR 35 TC 46 Z9 46 U1 2 U2 13 PU AMER SOCIOLOGICAL ASSOC PI WASHINGTON PA 1307 NEW YORK AVE NW #700, WASHINGTON, DC 20005-4712 USA SN 0022-1465 J9 J HEALTH SOC BEHAV JI J. Health Soc. Behav. PD SEP PY 2009 VL 50 IS 3 BP 245 EP 260 PG 16 WC Public, Environmental & Occupational Health; Psychology, Social SC Public, Environmental & Occupational Health; Psychology GA 477YK UT WOS:000268554700001 PM 19711804 ER PT J AU Baller, RD Richardson, KK AF Baller, Robert D. Richardson, Kelly K. TI The "'Dark Side" of the Strength of Weak Ties: The Diffusion of Suicidal Thoughts SO JOURNAL OF HEALTH AND SOCIAL BEHAVIOR LA English DT Article ID TELEVISION-NEWS STORIES; DELINQUENT PEERS; SOCIAL NETWORKS; STATUS ATTAINMENT; MENTAL-ILLNESS; SUBSTANCE USE; IDEATION; INFORMATION; DURKHEIM; BEHAVIOR AB Granovetter theory on the strength of weak ties motivates hypotheses on the diffusive nature of suicidal thoughts in the friendship networks of adolescents. Using data from the National Longitudinal Study of Adolescent Health, the effects of friends-of-friends attempting suicide on the suicidal thoughts of respondents are estimated. A focus on friends-of-friends permits a test of the weakties thesis because respondents are indirectly linked to friends-of-friends by "open ties" that are both structurally weak and used as bridges. Results for "at-risk" respondents-or those with certain behaviors, statuses, and experiences that create psychological predispositions to suicide-are consistent with Granovetter theory and thus reveal the "dark side" of the strength of weak ties as at-risk respondents are more likely to seriously think about committing suicide when a friend-of-a-friend attempts suicide, controlling for past suicidal thoughts by the respondent and attempts by friends, family, and students in the respondent school, among other control factors. Barriers to diffusion are also considered. C1 [Baller, Robert D.; Richardson, Kelly K.] Univ Iowa, US Dept Vet Affairs, Med Ctr, Iowa City, IA 52242 USA. [Richardson, Kelly K.] Univ Iowa, Vet Affairs Med Ctr, Iowa City, IA 52242 USA. RP Baller, RD (reprint author), Univ Iowa, US Dept Vet Affairs, Med Ctr, Iowa City, IA 52242 USA. RI Price, Katie/H-1931-2012 FU NICHD NIH HHS [P01-HD31921] NR 75 TC 21 Z9 21 U1 1 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-1465 EI 2150-6000 J9 J HEALTH SOC BEHAV JI J. Health Soc. Behav. PD SEP PY 2009 VL 50 IS 3 BP 261 EP 276 PG 16 WC Public, Environmental & Occupational Health; Psychology, Social SC Public, Environmental & Occupational Health; Psychology GA 477YK UT WOS:000268554700002 PM 19711805 ER PT J AU Stewart, GC Brooks, K Pratibhu, PP Tsang, SW Semigran, MJ Smith, CM Saniuk, C Camuso, JM Fang, JC Mudge, GH Couper, GS Baughman, KL Stevenson, LW AF Stewart, Garrick C. Brooks, Kimberly Pratibhu, Parakash P. Tsang, Sui W. Semigran, Marc J. Smith, Colleen M. Saniuk, Catherine Camuso, Janice M. Fang, James C. Mudge, Gilbert H. Couper, Gregory S. Baughman, Kenneth L. Stevenson, Lynne W. TI Thresholds of Physical Activity and Life Expectancy for Patients Considering Destination Ventricular Assist Devices SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID MECHANICAL CIRCULATORY SUPPORT; CHRONIC HEART-FAILURE; RANDOMIZED EVALUATION; PREDICTING MORTALITY; THERAPY; TRANSPLANTATION; SURVIVAL; MODEL; INTERMACS; SELECTION AB Background: Current implantable left ventricular assist devices (LVAD) improve survival and function for patients with very late stage heart failure (HF) but may also offer benefit before inotrope dependence. Debate continues about selection of HF patients for LVAD therapy. We sought to determine what level of personal risk and disability HF patients thought Would warrant LVAD therapy. Methods: The study included 105 patients with symptomatic HF and an LV ejection fraction (EF) < 35% who were given a written paragraph about LVADs and asked about circumstances under which they would consider such a device. New York Heart Association (NYHA) functional class, time trade-off utility, and patient-assessed functional score were determined. Results: Participants (mean age, 58 years) had an LVEF of 21%. The median duration of HF was 5 years, and 65% had a primary prevention implantable cardioverter defibrillator. Presented with a scenario of bed-ridden HF, 81% stated they would definitely or probably want an LVAD; 50% would consider LVAD to prolong survival if HF survival were predicted to be < 1 year and 75% if < 6 months. Meanwhile, 44% would consider LVAD if they could only walk < 1 block and 64% if they could not dress without stopping. Anticipated thresholds did not differ by NYHA class, time trade-off, or functional score. Conclusions: Patient thresholds for LVAD insertion parallel objective survival and functional data. HF patients would be receptive to referral for discussion of LVAD by the time expected mortality is within 6 to 12 months and activity remains limited to less than I block. J Heart Lung Transplant 2009;28:863-9. Copyright (C) 2009 by the International Society for Heart and Lung Transplantation. C1 [Stewart, Garrick C.; Brooks, Kimberly; Pratibhu, Parakash P.; Smith, Colleen M.; Saniuk, Catherine; Mudge, Gilbert H.; Couper, Gregory S.; Baughman, Kenneth L.; Stevenson, Lynne W.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Semigran, Marc J.; Camuso, Janice M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Tsang, Sui W.] Yale Univ, Dept Biostat, Sch Epidemiol & Publ Hlth, New Haven, CT USA. [Fang, James C.] Case Western Reserve Univ, Univ Hosp Cleveland, Div Cardiol, Cleveland, OH 44106 USA. RP Stewart, GC (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM gcstewart@partners.org NR 29 TC 23 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD SEP PY 2009 VL 28 IS 9 BP 863 EP 869 DI 10.1016/j.healun.2009.05.016 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 491VZ UT WOS:000269611100001 PM 19716036 ER PT J AU Huang, GC Smith, CC York, M Weingart, SN AF Huang, Grace C. Smith, C. Christopher York, Meghan Weingart, Saul N. TI Asking for Help: Internal Medicine Residents' Use of a Medical Procedure Service SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE procedural skills; resident supervision; central venous catherization AB BACKGROUND: Little is known about the professional help-seeking behavior of residents as they perform procedures in the hospital. OBJECTIVE: To determine when residents seek formal supervision to perform inpatient medical procedures. DESIGN: We conducted a prospective cohort study of resident physicians' use of formal Supervision through a medical procedure service (MPS) for placing central venous catheters (CVCs) and performing thoracenteses. We compared resident, procedure, and patient characteristics among MPS and non-MPS procedures. We performed bivariable and multivariable analyses to examine factors associated with use of the MPS. We also performed a subgroup analysis of non-MPS procedures to assess the influence of resident, procedure, and patient characteristics on the choice of informal supervision. SETTING: Boston teaching hospital. SUBJECTS: Sixty-nine internal medicine residents. MAIN OUTCOME MEASURE: Use of an elective MPS for formal faculty supervision. RESULTS: Among 191 procedures performed, 79 (41%) used the MPS. Residents were more likely to seek faculty supervision via the MPS among patients with 3 or more comorbidities (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.5). They were less likely to seek MPS supervision when procedures were performed urgently or emergently (OR, 0.4; 95% CI, 0.2-0.8). There were few differences in the characteristics of unsupervised and informally supervised procedures. CONCLUSIONS: Resident physicians appear to seek formal assistance appropriately for procedures they perform on sicker patients. Additional research is needed to understand whether overconfidence or poor access to attending physicians is responsible for their failure to seek consultation with urgent and emergent cases. Journal of Hospital Medicine 2009;4:404-409. (C) 2009 Society of Hospital Medicine. C1 [Huang, Grace C.; Smith, C. Christopher; York, Meghan; Weingart, Saul N.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Huang, Grace C.] Harvard Univ, Sch Med, Carl J Shapiro Inst Educ & Res, Boston, MA USA. [Weingart, Saul N.] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. RP Huang, GC (reprint author), 330 Brookline Ave,E ES 212, Boston, MA 02215 USA. EM ghuang@bidmc.harvard.edu OI Huang, Grace/0000-0003-2965-0341 FU Department of Medicine, Beth Israel Deaconess Medical Center; Carl J. Shapiro Institute for Education and Research at Harvard Medical School; U.S. Agency for Healthcare Research and Quality [K08 HS11644] FX This study was Supported by the Department of Medicine, Beth Israel Deaconess Medical Center, and by the Carl J. Shapiro Institute for Education and Research at Harvard Medical School and Beth Israel Deaconess Medical Center. Dr. Weingart was supported in part by a K08 clinical scientist career development award (K08 HS11644) from the U.S. Agency for Healthcare Research and Quality. NR 10 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD SEP PY 2009 VL 4 IS 7 BP 404 EP 409 DI 10.1002/jhm.434 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 496NL UT WOS:000269981200003 PM 19753572 ER PT J AU Grover, S Currier, PF Elinoff, JM Mouchantaf, KJ Katz, JT McMahon, GT AF Grover, Shilpa Currier, Paul F. Elinoff, Jason M. Mouchantaf, Kevin J. Katz, Joel T. McMahon, Graham T. TI Development of a Test to Evaluate Residents' Knowledge of Medical Procedures SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE medical procedures; residency training; test development ID INTERNAL-MEDICINE; SKILLS AB BACKGROUND AND AIM: Knowledge of core medical procedures is required by the American Board of Internal Medicine (ABIM) for certification. Efforts to improve the training of residents in these procedures have been limited by the absence of a validated tool for the assessment of knowledge. In this study we aimed to develop a standardized test of procedural knowledge in 3 medical procedures associated with potentially serious complications. METHODS: Placement of an arterial line, central venous catheter, and thoracentesis were selected for test development. Learning objectives and Multiple-choice questions were constructed for each topic. Content evidence was evaluated by critical care subspecialists. Item test characteristics were evaluated by administering the test to students, residents and specialty clinicians. Reliability of the 32-item instrument was established through its administration to 192 medical residents in 4 hospitals. RESULTS: Reliability of the instrument as measured by Cronbach's alpha was 0.79 and its test-retest reliability was 0.82. Median score was 53% on a test comprising elements deemed important by critical care subspecialists. Increasing number of procedures attempted, higher self-reported confidence, and increasing seniority were predictors of overall test scores. Procedural confidence correlated significantly with increasing seniority and experience. Residents performed few procedures. CONCLUSIONS: We have Successfully developed it standardized instrument to assess residents' cognitive competency for 3 common procedures. Residents' overall knowledge about procedures is poor. Experiential learning is the dominant source for knowledge improvement, but these experiences are increasingly rare. Journal of Hospital Medicine 2009;4:430-432. (C) 2009 Society of Hospital Medicine. C1 [McMahon, Graham T.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02114 USA. [Grover, Shilpa; Currier, Paul F.; Elinoff, Jason M.; Katz, Joel T.; McMahon, Graham T.] Harvard Univ, Sch Med, Boston, MA USA. [Currier, Paul F.; Elinoff, Jason M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Mouchantaf, Kevin J.] N Shore Med Ctr, Dept Med, Salem, MA USA. RP McMahon, GT (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, 221 Longwood Ave, Boston, MA 02114 USA. EM gmcmahon@partners.org RI McMahon, Graham/D-3740-2009 OI McMahon, Graham/0000-0003-4288-6535 FU Harvard University Provost FX Sponsored in part by an Innovation Grant in Instructional Computing from the Harvard University Provost. NR 10 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD SEP PY 2009 VL 4 IS 7 BP 430 EP 432 DI 10.1002/jhm.507 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 496NL UT WOS:000269981200007 PM 19753571 ER PT J AU Rollins, BJ AF Rollins, Barrett J. TI Where the Confusion Began: Cloning the First Chemokine Receptors SO JOURNAL OF IMMUNOLOGY LA English DT Editorial Material ID NEUTROPHIL CHEMOTACTIC FACTOR; HUMAN INTERLEUKIN-8 RECEPTOR; THYMOCYTE-ACTIVATING FACTOR; PEPTIDE; PURIFICATION; LEUKOCYTES; CYTOKINES; CDNA; NAF C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Smith 758,44 Binney St, Boston, MA 02115 USA. EM barrett_rollins@dfci.harvard.edu NR 20 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2009 VL 183 IS 5 BP 2893 EP 2894 DI 10.4049/jimmunol.0990065 PG 2 WC Immunology SC Immunology GA 489AI UT WOS:000269391400003 PM 19696427 ER PT J AU Lienenklaus, S Cornitescu, M Zietara, N Lyszkiewicz, M Gekara, N Jablonska, J Edenhofer, F Rajewsky, K Bruder, D Hafner, M Staeheli, P Weiss, S AF Lienenklaus, Stefan Cornitescu, Marius Zietara, Natalia Lyszkiewicz, Marcin Gekara, Nelson Jablonska, Jadwiga Edenhofer, Frank Rajewsky, Klaus Bruder, Dunja Hafner, Martin Staeheli, Peter Weiss, Siegfried TI Novel Reporter Mouse Reveals Constitutive and Inflammatory Expression of IFN-beta In Vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GREEN FLUORESCENT PROTEIN; INFLUENZA-A VIRUS; INTERFERON-ALPHA; MICE; INDUCTION; INFECTION; CELLS; PATHOGENESIS; FIBROBLASTS; CYTOKINES AB Type I IFN is a major player in innate and adaptive immune responses. Besides, it is involved in organogenesis and tumor development. Generally, IFN responses are amplified by an autocrine loop with IFN-beta as the priming cytokine. However, due to the lack of sensitive detection systems, where and how type I IFN is produced in vivo is still poorly understood. In this study, we describe a luciferase reporter mouse, which allows tracking of IFN-beta gene induction in vivo. Using this reporter mouse, we reveal strong tissue-specific induction of IFN-beta following infection with influenza or La Crosse virus. Importantly, this reporter mouse also allowed us to visualize that IFN-beta is expressed constitutively in several tissues. As suggested before, low amounts of constitutively produced IFN might maintain immune cells in an activated state ready for a timely response to pathogens. Interestingly, thymic epithelial cells were the major source of IFN-beta under noninflammatory conditions. This relatively high constitutive expression was controlled by the NF Aire and might influence induction of tolerance or T cell development. The Journal of Immunology, 2009, 183: 3229-3236. C1 [Lienenklaus, Stefan; Zietara, Natalia; Lyszkiewicz, Marcin; Gekara, Nelson; Jablonska, Jadwiga; Bruder, Dunja; Weiss, Siegfried] Helmholtz Ctr Infect Res, Braunschweig, Germany. [Cornitescu, Marius; Staeheli, Peter] Univ Freiburg, Dept Virol, Freiburg, Germany. [Edenhofer, Frank] Univ Bonn, Stem Cell Engn Grp, D-5300 Bonn, Germany. [Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Hafner, Martin] Univ Cologne, Inst Genet, D-5000 Cologne, Germany. RP Lienenklaus, S (reprint author), Helmholtz Ctr Infect Res, Inhoffenstr 7, Braunschweig, Germany. EM stl@gbf.de RI Hafner, Martin/B-9040-2008; OI Hafner, Martin/0000-0003-0769-1812; Edenhofer, Frank/0000-0002-6489-714X; Lienenklaus, Stefan/0000-0003-4790-3445 FU German Research Council (DFG); EC; Marie Curie Action Miditrain [MEST-CT-2004-504990]; Helmholtz Gemeinschaft via Helmholtz International Research School for Infection Biology; Deutsche Krebshilfe; Kultusministerium of Niedersachsen; Lichtenberg PhD program FX This work was supported in part by the German Research Council (DFG), the EC via Clinigene and the Marie Curie Action Miditrain MEST-CT-2004-504990, the Helmholtz Gemeinschaft via Helmholtz International Research School for Infection Biology, the Deutsche Krebshilfe, and the Kultusministerium of Niedersachsen via the Lichtenberg PhD program. NR 34 TC 83 Z9 84 U1 2 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2009 VL 183 IS 5 BP 3229 EP 3236 DI 10.4049/jimmunol.0804277 PG 8 WC Immunology SC Immunology GA 489AI UT WOS:000269391400041 PM 19667093 ER PT J AU Aribodor, DN Nwaorgu, OC Eneanya, CI Okoli, I Pukkila-Worley, R Etaga, HO AF Aribodor, Dennis N. Nwaorgu, Obioma C. Eneanya, Christine I. Okoli, Ikechukwu Pukkila-Worley, Reed Etaga, Harrison O. TI Association of low birth weight and placental malarial infection in Nigeria SO JOURNAL OF INFECTION IN DEVELOPING COUNTRIES LA English DT Article DE malaria; placenta; pregnancy; newborns; low birth weight AB Background: Malaria causes significant morbidity and mortality among pregnant women in Nigeria. However, the contribution of malaria infection to neonatal development is incompletely understood. Here we determined the prevalence of placental malarial infection in six communities in Anambra State, Nigeria, between 2005 and 2006, and compare these data to neonatal birth weight. Methodology: Blood samples were obtained from the placenta of 500 parturient mothers and examined for the presence of malaria parasites. Newborn birth weight was then compared with the malaria status of their mothers. Results: Placental malarial infection was found in 322 of 500 mothers (64.4%). The prevalence of infection did not differ among the six different Nigerian communities (P = 0.978). Furthermore, there was no difference in infection rates between rural and urban areas (64.9% vs. 64.0%, respectively, P = 0.827). Interestingly, neonates born from mothers with placental malaria had lower birth weights than neonates born from uninfected mothers [2500 g (range 1900 g - 3200 g) vs. 3800 g (range 3200 g - 4700 g), P < 0.001]. Forty-five percent (145/322) of the newborns born from infected mothers were of low birth weight (defined as birth weight less than 2,500 g). Conclusion: Malaria infection during pregnancy is common in Nigeria and is likely associated with low newborn birth weight. C1 [Okoli, Ikechukwu; Pukkila-Worley, Reed] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Aribodor, Dennis N.; Nwaorgu, Obioma C.; Eneanya, Christine I.] Nnamdi Azikiwe Univ, Dept Parasitol & Entomol, Awka, Anambra State, Nigeria. [Etaga, Harrison O.] Nnamdi Azikiwe Univ, Dept Stat, Awka, Anambra State, Nigeria. RP Okoli, I (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM ikeokoli@msn.com NR 14 TC 6 Z9 6 U1 0 U2 0 PU J INFECTION DEVELOPING COUNTRIES PI TRAMANIGLIO PA JIDC CENT OFF PORTO CONTE RICERCHE RES CTR, S P 55, PORTO CONTE CAPO CACCIA KM 8.400 LOC, TRAMANIGLIO, 07041, ITALY SN 1972-2680 J9 J INFECT DEV COUNTR JI J. Infect. Dev. Ctries. PD SEP PY 2009 VL 3 IS 8 BP 620 EP 623 PG 4 WC Infectious Diseases SC Infectious Diseases GA V22BQ UT WOS:000208251100007 PM 19801805 ER PT J AU Cubeddu, RJ Inglessis, I Palacios, IF AF Cubeddu, Roberto J. Inglessis, Ignacio Palacios, Igor F. TI Structural Heart Disease Interventions: An Emerging Discipline in Cardiovascular Medicine SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Review ID MITRAL-VALVE REPAIR; BALLOON COARCTATION ANGIOPLASTY; AORTIC-STENOSIS; PULMONARY-VALVE; ANNULAR REDUCTION; FOLLOW-UP; VALVULOPLASTY; IMPLANTATION; EXPERIENCE; MODEL AB Within the past decade we have witnessed the exponential growth of novel percutaneous transcatheter therapies for the treatment of valvular and congenital heart disorders among others Consequently a new field has emerged in the world of adult cardiovascular medicine known as structural heart disease interventions We herein provide a contemporary review highlighting many of the important historical landmarks that have set the stage for the development of this new and exciting subspecialty and introduce a comprehensive overview of the structured training and challenges that will be required to master this field To our knowledge our Structural Heart Disease fellowship constitutes one of the very first dedicated training programs in the United States We believe our experience may be of value to other similar emerging programs across the country and the world C1 [Cubeddu, Roberto J.; Inglessis, Ignacio; Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, 55 Fruit St Suite GRB 800, Boston, MA 02114 USA. NR 29 TC 2 Z9 2 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 EI 1557-2501 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD SEP PY 2009 VL 21 IS 9 BP 478 EP 482 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 687VT UT WOS:000284807000014 PM 19726823 ER PT J AU Pietramaggiori, G Scherer, SS Alperovich, M Chen, B Orgill, DP Wagers, AJ AF Pietramaggiori, Giorgio Scherer, Sandra S. Alperovich, Michael Chen, Bin Orgill, Dennis P. Wagers, Amy J. TI Improved Cutaneous Healing in Diabetic Mice Exposed to Healthy Peripheral Circulation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID BRONCHOALVEOLAR MACROPHAGE DEFENSE; PLATELET-RICH PLASMA; GROWTH-FACTOR; HEMATOPOIETIC STEM; BONE-MARROW; ANGIOGENESIS; IMPAIRMENT; MOUSE; CELLS; NEUTROPHILS AB Impaired repair of skin defects is a major complication of diabetes; yet, the pathophysiology of diabetic (db) wound healing remains largely opaque. Here, we investigate the role of humoral factors in modulating db wound repair by generating chimeric animals through parabiotic joining of wild-type (wt) and diabetic (db/db) mice. This strategy allows wounds on healing-deficient db/db mice to be exposed to factors derived from the wt circulation at physiologically appropriate concentrations. When compared with db controls, chimeric db/db animals showed significantly improved healing of full-thickness, cutaneous wounds, with enhanced granulation tissue formation, angiogenesis, cell proliferation, and collagen deposition. Glycemic control was unaffected by parabiosis; however, the distribution of circulating leukocytes, altered in db controls, normalized in db-chimeras. Both wt and db cells were recruited from circulation into db wounds, but wt cells never exceeded 20% of total cells. Improved angiogenesis persisted in db-chimeras separated 24 hours after wounding, suggesting the existence of long-term normalizing factors. This study establishes a new model for studying db wound healing, and shows a key role for circulating factors in normalizing wound repair in diabetes. C1 [Pietramaggiori, Giorgio; Scherer, Sandra S.; Alperovich, Michael; Chen, Bin; Orgill, Dennis P.] Harvard Univ, Div Plast Surg, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Pietramaggiori, Giorgio; Scherer, Sandra S.; Alperovich, Michael; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Joslin Diabet Ctr, Boston, MA 02115 USA. [Pietramaggiori, Giorgio; Scherer, Sandra S.; Alperovich, Michael; Wagers, Amy J.] Harvard Stem Cell Inst, Boston, MA USA. [Pietramaggiori, Giorgio] Univ Geneva, Div Plast Surg, Geneva, Switzerland. RP Orgill, DP (reprint author), Harvard Univ, Div Plast Surg, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM amy.wagers@joslin.harvard.edu RI Chen, Bin/I-6677-2013; OI Orgill, Dennis/0000-0002-8279-7310 FU NIH/NIDDK [5 P30 DK36836-20]; Joslin Diabetes Center FX We would like to acknowledge support for these studies from NIH/NIDDK (5 P30 DK36836-20 to AJW), from the Joslin Diabetes Center, and from a 3M Wound Healing Fellowship (to GP). we thank Drs. M Cerletti, S Mayack, I Min, and G Murphy for helpful discussions, and S Jurga for excellent technical assistance. We acknowledge Dr R Kulkarni for coordinating the 5P30 DK 36836 Specialized Assay Core at the Joslin Diabetes Center. Finally, we thank Joyce LaVecchio and Girijesh Buruzula for expert flow cytometry support at the Joslin Diabetes Center/Harvard Stem Cell Institute Flow Core. NR 38 TC 24 Z9 24 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2009 VL 129 IS 9 BP 2265 EP 2274 DI 10.1038/jid.2009.60 PG 10 WC Dermatology SC Dermatology GA 483CN UT WOS:000268939700026 PM 19295612 ER PT J AU Jalili, A Wagner, C Mertz, KD Pashenkov, M Lupien, M Brunet, JP Ramaswamy, S Golub, TR Stingl, G Wagner, SN AF Jalili, A. Wagner, C. Mertz, K. D. Pashenkov, M. Lupien, M. Brunet, J. P. Ramaswamy, S. Golub, T. R. Stingl, G. Wagner, S. N. TI AP-1 inhibition identifies cooperation of INK4 and Cip/Kip signaling pathways to suppress human melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 39th Annual European-Society-for-Dermatological-Research CY SEP 10, 2009 CL Budapest, HUNGARY SP European Soc Dermatol Res C1 [Jalili, A.; Wagner, C.; Mertz, K. D.; Pashenkov, M.; Stingl, G.; Wagner, S. N.] Med Univ Vienna, Dept Dermatol, DIAID, Vienna, Austria. [Lupien, M.] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. [Brunet, J. P.; Golub, T. R.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Ramaswamy, S.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Ramaswamy, S.] Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2009 VL 129 BP S37 EP S37 PG 1 WC Dermatology SC Dermatology GA 487IA UT WOS:000269264100221 ER PT J AU Oberholzer, PA Karpova, MB Zipser, MC Lin, WM Girardi, M MacConaill, LE Kehoe, SM Garraway, LA Dummer, R AF Oberholzer, P. A. Karpova, M. B. Zipser, M. C. Lin, W. M. Girardi, M. MacConaill, L. E. Kehoe, S. M. Garraway, L. A. Dummer, R. TI High-throughput mutation profiling of CTCL samples using OncoMap SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 39th Annual European-Society-for-Dermatological-Research CY SEP 10, 2009 CL Budapest, HUNGARY SP European Soc Dermatol Res C1 [Oberholzer, P. A.; MacConaill, L. E.; Garraway, L. A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Karpova, M. B.; Zipser, M. C.] Univ Zurich Hosp, Zurich, Switzerland. [Lin, W. M.; Girardi, M.] Yale Univ, Sch Med, New Haven, CT USA. [Kehoe, S. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2009 VL 129 BP S46 EP S46 PG 1 WC Dermatology SC Dermatology GA 487IA UT WOS:000269264100273 ER PT J AU Hu, W Bielawski, J Samad, F Merrill, AH Cowart, LA AF Hu, Wei Bielawski, Jacek Samad, Fahumiya Merrill, Alfred H., Jr. Cowart, L. Ashley TI Palmitate increases sphingosine-1-phosphate in C2C12 myotubes via upregulation of sphingosine kinase message and activity SO JOURNAL OF LIPID RESEARCH LA English DT Article DE free fatty acid; sphingolipid; ceramide; skeletal muscle; insulin resistance; diabetes; obesity; lipotoxicity ID SATURATED FATTY-ACIDS; INDUCED INSULIN-RESISTANCE; TANDEM MASS-SPECTROMETRY; SKELETAL-MUSCLE CELLS; CERAMIDE KINASE; SPHINGOLIPID METABOLISM; SERINE PALMITOYLTRANSFERASE; QUANTITATIVE-ANALYSIS; SIGNAL-TRANSDUCTION; HUMAN HEAD AB Studies in skeletal muscle demonstrate that elevation of plasma FFAs increases the sphingolipid ceramide. We aimed to determine the impact of FFA oversupply on total sphingolipid profiles in a skeletal muscle model. C2C12 myotubes were treated with palmitate (PAL). Lipidomics analysis revealed pleiotropic effects of PAL on cell sphingolipids not limited to ceramides. (13)C labeling demonstrated that PAL activated several branches of sphingolipid synthesis by distinct mechanisms. Intriguingly, PAL increased sphingosine-1-phosphate independently of de novo synthesis. Quantitative real-time PCR demonstrated that PAL increased sphingosine kinase 1 (SK1) mRNA by approximately 4-fold. This was accompanied by a 2.3-fold increase in sphingosine kinase enzyme activity. This upregulation did not occur upon treatment with oleate, suggesting some level of specificity for PAL. These findings were recapitulated in the diet-induced obesity mouse model, in which high-fat feeding increased SK1 message in skeletal muscle over 2.3-fold. These data suggest that the impact of elevated FFA on sphingolipids reaches beyond ceramides and de novo sphingolipid synthesis. Moreover, these findings identify PAL as a novel regulatory stimulus for SK1.-Hu, W., J. Bielawski, F. Samad, A. H. Merrill, Jr., and L. A. Cowart. Palmitate increases sphingosine-1-phosphate in C2C12 myotubes via upregulation of sphingosine kinase message and activity. J. Lipid Res. 2009. 50: 1852-1862. C1 [Hu, Wei; Bielawski, Jacek; Cowart, L. Ashley] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Samad, Fahumiya] Torrey Pines Inst Mol Studies, San Diego, CA USA. [Merrill, Alfred H., Jr.] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. [Merrill, Alfred H., Jr.] Georgia Inst Technol, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA. [Cowart, L. Ashley] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Cowart, LA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM cowartl@musc.edu FU Department of Veteran's Affairs; National Institutes of Health COBRE FX This work was supported by funding from the Department of Veteran's Affairs and the National Institutes of Health COBRE in Lipidomics and Pathobiology at the Medical University of South Carolina to L.A.C. NR 62 TC 31 Z9 31 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2009 VL 50 IS 9 BP 1852 EP 1862 DI 10.1194/jlr.M800635-JLR200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 484LO UT WOS:000269046600013 PM 19369694 ER PT J AU Guseh, JS Brendel, RW Brendel, DH AF Guseh, J. S., II Brendel, R. W. Brendel, D. H. TI Medical professionalism in the age of online social networking SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID PHYSICIANS; GIFTS; ME AB The rapid emergence and exploding usage of online social networking forums, which are frequented by millions, present clinicians with new ethical and professional challenges. Particularly among a younger generation of physicians and patients, the use of online social networking forums has become widespread. In this article, we discuss ethical challenges facing the patient doctor relationship as a result of the growing use of online social networking forums. We draw upon one heavily used and highly trafficked forum, Facebook, to illustrate the elements of these online environments and the ethical challenges peculiar to their novel form of exchange. Finally, we present guidelines for clinicians to negotiate responsibly and professionally their possible uses of these social forums. C1 [Brendel, R. W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Brendel, D. H.] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. RP Brendel, DH (reprint author), Harvard Univ, McLean Hosp, Sch Med, 115 Mill St, Belmont, MA 02178 USA. EM dbrendel@partners.org RI Roundtree, Aimee/B-8838-2012 NR 11 TC 72 Z9 76 U1 0 U2 11 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD SEP PY 2009 VL 35 IS 9 BP 584 EP 586 DI 10.1136/jme.2009.029231 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 488YB UT WOS:000269385200013 PM 19717700 ER PT J AU Ortigo, KM Westen, D Bradley, B AF Ortigo, Kile M. Westen, Drew Bradley, Bekh TI Personality Subtypes of Suicidal Adults SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Suicide; personality; subtypes; typology ID ASSESSING AXIS II; TOWER-OF-BABEL; CLUSTER-ANALYSIS; REVISED NOMENCLATURE; DISORDER DIAGNOSIS; EATING-DISORDERS; 5-FACTOR MODEL; RISK-FACTORS; CLASSIFICATION; DEPRESSION AB Research into personality factors related to suicidality suggests substantial variability among suicide attempters. A potentially useful approach that accounts for this complexity is personality subtyping. As part of a large sample looking at personality pathology, this study used Q-factor analysis to identify subtypes of 311 adult suicide attempters using Shedler-Westen Assessment Procedure-II personality profiles. Identified subtypes included internalizing, emotionally dysregulated, dependent, hostile-isolated, psychopathic, and anxious serializing. Subtypes differed in hypothesized ways on criterion variables that address their construct validity, including adaptive functioning, Axis I and II comorbidity, and etiology-related variables (e.g., history of abuse). Furthermore, dimensional ratings of the subtypes predicted adaptive functioning above DSM-based diagnoses and symptoms. C1 [Ortigo, Kile M.; Westen, Drew] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Bradley, Bekh] US Dept Vet Affairs, Med Ctr, Atlanta, GA USA. [Bradley, Bekh] US Amer & Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA USA. RP Ortigo, KM (reprint author), Emory Univ, Dept Psychol, 36 Eagle Row, Atlanta, GA 30322 USA. EM kortigo@emory.edu RI Bradley, Bekh/H-8399-2012 FU NIMH [MH-62377]; American Suicide Prevention Foundation FX Supported by NIMH grant MH-62377 (to D.W.) and an American Suicide Prevention Foundation Young Investigator Grant (to B.B.). NR 56 TC 11 Z9 12 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD SEP PY 2009 VL 197 IS 9 BP 687 EP 694 DI 10.1097/NMD.0b013e3181b3b13f PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 494UN UT WOS:000269844100008 PM 19752649 ER PT J AU Bullain, SS Sahin, A Szentirmai, O Sanchez, C Lin, N Baratta, E Waterman, P Weissleder, R Mulligan, RC Carter, BS AF Bullain, Szofia S. Sahin, Ayguen Szentirmai, Oszkar Sanchez, Carlos Lin, Ning Baratta, Elizabeth Waterman, Peter Weissleder, Ralph Mulligan, Richard C. Carter, Bob S. TI Genetically engineered T cells to target EGFRvIII expressing glioblastoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Adoptive immunotherapy; Glioma; Chimeric immune receptor; Chimeric T cell receptor; EGFRvIII; MR1 ID ANTIGEN RECEPTOR; MALIGNANT GLIOMA; PHAGE DISPLAY; GROWTH; LYMPHOCYTES; TUMORS; CD28; IMMUNOTHERAPY; IMMUNOTOXINS; SPECIFICITY AB Glioblastoma remains a significant therapeutic challenge, warranting further investigation of novel therapies. We describe an immunotherapeutic strategy to treat glioblastoma based on adoptive transfer of genetically modified T-lymphocytes (T cells) redirected to kill EGFRvIII expressing gliomas. We constructed a chimeric immune receptor (CIR) specific to EGFRvIII, (MR1-zeta). After in vitro selection and expansion, MR1-zeta genetically modified primary human T-cells specifically recognized EGFRvIII-positive tumor cells as demonstrated by IFN-gamma secretion and efficient tumor lysis compared to control CIRs defective in EGFRvIII binding (MRB-zeta) or signaling (MR1-del zeta). MR1-zeta expressing T cells also inhibited EGFRvIII-positive tumor growth in vivo in a xenografted mouse model. Successful targeting of EGFRvIII-positive tumors via adoptive transfer of genetically modified T cells may represent a new immunotherapy strategy with great potential for clinical applications. C1 [Bullain, Szofia S.; Sahin, Ayguen; Szentirmai, Oszkar; Sanchez, Carlos; Lin, Ning; Baratta, Elizabeth; Carter, Bob S.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Waterman, Peter; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Mulligan, Richard C.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Carter, BS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, 55 Fruit St,Yawkey 9026, Boston, MA 02114 USA. EM bcarter@partners.org FU Goldhirsh Foundation; Brain Tumor Society,; Rappaport Foundation; NIH/NCI [CA 69246 P01] FX The work was funded by the Goldhirsh Foundation in memory of Bernie Goldhirsh, the Brain Tumor Society, the Rappaport Foundation and NIH/NCI CA 69246 P01 grant "Gene Therapy for Brain Tumors.'' Dr. John Gray assisted with production of the MR1 vector. NR 31 TC 29 Z9 29 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2009 VL 94 IS 3 BP 373 EP 382 DI 10.1007/s11060-009-9889-1 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 486PI UT WOS:000269209100008 PM 19387557 ER PT J AU Khrapko, K Kraytsberg, Y Guo, X Nicholas, A AF Khrapko, K. Kraytsberg, Y. Guo, X. Nicholas, A. TI MTDNA MUTATIONS IN BRAIN AGING SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 22nd Biennial Meeting of the International-Society-of-Neurochemistry/Asian-Pacific-Society-for-Neuroc hemistry CY AUG 23-29, 2009 CL Busan, SOUTH KOREA SP Int Soc Neurochem, Asian Pacific Soc C1 [Khrapko, K.; Kraytsberg, Y.; Guo, X.; Nicholas, A.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2009 VL 110 BP 75 EP 75 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 477WT UT WOS:000268550400205 ER PT J AU Shioda, N Beppu, H Kitajima, I Fukunaga, K AF Shioda, N. Beppu, H. Kitajima, I Fukunaga, K. TI ABERRANT CAMKII ACTIVITY IS ASSOCIATED WITH ABNORMAL DENDRITIC SPINE FORMATION VIA RAC1-GEF/PAK SIGNALING IN ATRX MUTANT MICE SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 22nd Biennial Meeting of the International-Society-of-Neurochemistry/Asian-Pacific-Society-for-Neuroc hemistry CY AUG 23-29, 2009 CL Busan, SOUTH KOREA SP Int Soc Neurochem, Asian Pacific Soc C1 [Shioda, N.; Fukunaga, K.] Tohoku Univ, Dept Pharmacol, Grad Sch Pharmaceut Sci, Sendai, Miyagi 980, Japan. [Beppu, H.] Harvard Univ, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Kitajima, I] Toyama Univ, Dept Clin & Mol Pathol, Fac Med, Toyama 930, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2009 VL 110 BP 201 EP 201 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 477WT UT WOS:000268550400553 ER PT J AU Xing, CH Lee, S Kim, WJ Yang, YG Wang, XY Lo, EH AF Xing, C. H. Lee, S. Kim, W. J. Yang, Y. G. Wang, X. Y. Lo, E. H. TI NEUROVASCULAR EFFECTS OF CD47: PROMOTION OF CELL DEATH, INFLAMMATION AND SUPPRESSION OF ANGIOGENESIS IN BRAIN ENDOTHELIAL CELLS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 22nd Biennial Meeting of the International-Society-of-Neurochemistry/Asian-Pacific-Society-for-Neuroc hemistry CY AUG 23-29, 2009 CL Busan, SOUTH KOREA SP Int Soc Neurochem, Asian Pacific Soc C1 [Xing, C. H.; Kim, W. J.; Wang, X. Y.; Lo, E. H.] Harvard Univ, Dept Radiol & Neurol, Neuroprotect Res Lab, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. [Lee, S.] Cheju Natl Univ, Dept Biol, Cheju, South Korea. [Yang, Y. G.] Harvard Univ, Dept Med, Transplantat Biol Res Ctr, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2009 VL 110 BP 206 EP 206 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 477WT UT WOS:000268550400570 ER PT J AU Kegel, KB Sapp, E Alexander, J Valencia, A Reeves, P Li, XY Masso, N Sobin, L Aronin, N DiFiglia, M AF Kegel, Kimberly B. Sapp, Ellen Alexander, Jonathan Valencia, Antonio Reeves, Patrick Li, Xueyi Masso, Nicholas Sobin, Lindsay Aronin, Neil DiFiglia, Marian TI Polyglutamine expansion in huntingtin alters its interaction with phospholipids SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cardiolipin; dynamin; Huntington's disease; large unilamellar vesicles; phosphoinositide; phosphoinositol 3-kinase ID RECEPTOR TYROSINE KINASES; 3-KINASE LIPID PRODUCTS; MAPK SIGNALING PATHWAYS; DISEASE GENE HOMOLOG; MUTANT HUNTINGTIN; GROWTH-FACTOR; PHOSPHOINOSITIDE METABOLISM; WIDESPREAD EXPRESSION; MEDIATED ENDOCYTOSIS; ACIDIC PHOSPHOLIPIDS AB Huntingtin has an expanded polyglutamine tract in patients with Huntington's disease. Huntingtin localizes to intracellular and plasma membranes but the function of huntingtin at membranes is unknown. Previously we reported that exogenously expressed huntingtin bound pure phospholipids using protein-lipid overlays. Here we show that endogenous huntingtin from normal(Hdh(7Q/7Q)) mouse brain and mutant huntingtin from Huntington's disease (Hdh(140Q/140Q)) mouse brain bound to large unilamellar vesicles containing phosphoinositol (PI) PI 3,4-bisphosphate, PI 3,5-bisphosphate, and PI 3,4,5-triphosphate [PI(3,4,5)P3]. Huntingtin interactions with multivalent phospholipids were similar to those of dynamin. Mutant huntingtin associated more with phosphatidylethanolamine and PI(3,4,5) P3 than did wild-type huntingtin, and associated with other phospholipids not recognized by wild-type huntingtin. Wild-type and mutant huntingtin also bound to large unilamellar vesicles containing cardiolipin, a phospholipid specific to mitochondrial membranes. Maximal huntingtin-phospholipid association required inclusion of huntingtin amino acids 171-287. Endogenous huntingtin recruited to the plasma membrane in cells that incorporated exogenous PI 3,4-bisphosphate and PI(3,4,5)P3 or were stimulated by platelet-derived growth factor or insulin growth factor 1, which both activate PI 3-kinase. These data suggest that huntingtin interacts with membranes through specific phospholipid associations and that mutant huntingtin may disrupt membrane trafficking and signaling at membranes. C1 [Kegel, Kimberly B.; Sapp, Ellen; Alexander, Jonathan; Valencia, Antonio; Reeves, Patrick; Li, Xueyi; Masso, Nicholas; Sobin, Lindsay; DiFiglia, Marian] Massachusetts Gen Hosp, Dept Neurol, Lab Cellular Neurobiol, Charlestown, MA USA. [Aronin, Neil] Univ Massachusetts, Sch Med, Dept Med & Cell Biol, Worcester, MA USA. RP Kegel, KB (reprint author), Massachusetts Gen Hosp East, Dept Neurol, 114 16th St,Room 2150, Charlestown, MA 02129 USA. EM kkegel@partners.org NR 56 TC 40 Z9 41 U1 0 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2009 VL 110 IS 5 BP 1585 EP 1597 DI 10.1111/j.1471-4159.2009.06255.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 482AA UT WOS:000268854200020 PM 19566678 ER PT J AU Dulla, CG Frenguelli, BG Staley, KJ Masino, SA AF Dulla, Chris G. Frenguelli, Bruno G. Staley, Kevin J. Masino, Susan A. TI Intracellular Acidification Causes Adenosine Release During States of Hyperexcitability in the Hippocampus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CA3 NETWORK ACTIVITY; RAT HIPPOCAMPUS; EXCITATORY TRANSMISSION; ELECTRICAL-STIMULATION; SYNAPTIC-TRANSMISSION; EPILEPTIFORM ACTIVITY; NMDA RECEPTORS; MICE LACKING; NEURONS AB Dulla CG, Frenguelli BG, Staley KJ, Masino SA. Intracellular acidification causes adenosine release during states of hyperexcitability in the hippocampus. J Neurophysiol 102: 1984-1993, 2009. First published July 22, 2009; doi:10.1152/jn.90695.2008. Decreased pH increases extracellular adenosine in CNS regions as diverse as hippocampus and ventral medulla. However, thus far there is no clear consensus whether the critical pH change is a decrease in intracellular and/or extracellular pH. Previously we showed that a decrease in extracellular pH is necessary and a decrease in intracellular pH alone is not sufficient, to increase extracellular adenosine in an acute hippocampal slice preparation. Here we explored further the role of intracellular pH under different synaptic conditions in the hippocampal slice. When synaptic excitability was increased, either during gamma-aminobutyric acid type A receptor blockade in CA1 or after the induction of persistent bursting in CA3, a decrease in intracellular pH alone was now sufficient to: 1) elevate extracellular adenosine concentration, 2) activate adenosine A 1 receptors, 3) decrease excitatory synaptic transmission (CA1), and 4) attenuate burst frequency in an in vitro seizure model (CA3). Hippocampal slices obtained from adenosine A 1 receptor knockout mice did not exhibit these pH-mediated effects on synaptic transmission, further confirming the role of adenosine acting at the adenosine A 1 receptor. Taken together, these data strengthen and add significantly to the evidence outlining a change in pH as an important stimulus influencing extracellular adenosine. In addition, we identify conditions under which intracellular pH plays a dominant role in regulating extracellular adenosine concentrations. C1 [Masino, Susan A.] Trinity Coll, Neurosci Program, Hartford, CT 06106 USA. [Masino, Susan A.] Trinity Coll, Dept Psychol, Hartford, CT 06106 USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Frenguelli, Bruno G.] Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England. [Dulla, Chris G.] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. RP Masino, SA (reprint author), Trinity Coll, Neurosci Program, 300 Summit St, Hartford, CT 06106 USA. EM Susan.Masino@trincoll.edu RI Frenguelli, Bruno/C-5007-2015 OI Frenguelli, Bruno/0000-0001-7214-3172 FU American Epilepsy Foundation; Epilepsy Research UK; National Institute of Neurological Disorders and Stroke [NS-34360-12, NS-29173, NS-61290]; National Science Foundation; Howard Hughes institutional award FX This work was supported by an American Epilepsy Foundation predoctoral fellowship to C. G. Dulla; Epilepsy Research UK grant to B. G. Frenguelli; National Institute of Neurological Disorders and Stroke Grants NS-34360-12 to K. J. Staley; NS-29173, and NS-61290, National Science Foundation, and a Howard Hughes institutional award to Trinity College to S. A. Masino. NR 47 TC 18 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2009 VL 102 IS 3 BP 1984 EP 1993 DI 10.1152/jn.90695.2008 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 490JJ UT WOS:000269496700056 PM 19625534 ER PT J AU Wortzel, HS Frey, KL Anderson, CA Arciniegas, DB AF Wortzel, Hal S. Frey, Kimberly L. Anderson, C. Alan Arciniegas, David B. TI Subtle Neurological Signs Predict the Severity of Subacute Cognitive and Functional Impairments After Traumatic Brain Injury SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID FRONTAL ASSESSMENT BATTERY; PRIMITIVE REFLEXES; HEALTH; FAB AB The presence of paratonia and primitive reflexes ("frontal release signs"), such as glabellar, snout, suck, grasp, and palmomental responses, after traumatic brain injury predicts performance on bedside cognitive assessments, level of functional independence, and duration of acute inpatient rehabilitation. (The journal of Neuropsychiatry and Clinical Neurosciences 2009; 21:463-466) C1 [Wortzel, Hal S.; Frey, Kimberly L.; Arciniegas, David B.] HealthONE Spalding Rehabil Hosp, Brain Injury Rehabil Unit, Aurora, CO USA. [Wortzel, Hal S.; Anderson, C. Alan; Arciniegas, David B.] Denver Vet Affairs Med Ctr, VISN 19, MIRECC, Denver, CO 80220 USA. [Wortzel, Hal S.; Frey, Kimberly L.; Anderson, C. Alan; Arciniegas, David B.] Univ Colorado, Sch Med, Dept Psychiat, Neurobehav Disorders Program, Denver, CO 80262 USA. [Anderson, C. Alan; Arciniegas, David B.] Univ Colorado, Sch Med, Dept Neurol, Behav Neurol Sect, Denver, CO USA. RP Wortzel, HS (reprint author), Denver Vet Affairs Med Ctr, VISN 19, MIRECC, 1055 Clermont St,Room 4E130, Denver, CO 80220 USA. EM Hal.wortzel@ucdenver.edu FU Health ONE Spalding Rehabilitation Hospital (KLF, DBA); VISN-19 MIRECC (HSW, CAA, DBA) FX This work was supported by Health ONE Spalding Rehabilitation Hospital (KLF, DBA) and the VISN-19 MIRECC (HSW, CAA, DBA). The authors are grateful to Kenneth L. Tyler, M.D., for his assistance during the preparation of this manuscript. NR 15 TC 5 Z9 6 U1 3 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2009 VL 21 IS 4 BP 463 EP 466 PG 4 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 526RR UT WOS:000272311300014 PM 19996256 ER PT J AU Gabeau-Lacet, D Aghi, M Betensky, RA Barker, FG Loeffler, JS Louis, DN AF Gabeau-Lacet, Darlene Aghi, Manish Betensky, Rebecca A. Barker, Fred G. Loeffler, Jay S. Louis, David N. TI Bone involvement predicts poor outcome in atypical meningioma Clinical article SO JOURNAL OF NEUROSURGERY LA English DT Article DE atypical meningioma; bone invasion; subtotal resection; progression; survival ID INTRACRANIAL MENINGIOMA; CRANIAL HYPEROSTOSIS; MALIGNANT MENINGIOMAS; MULTIVARIATE-ANALYSIS; PROGNOSTIC-FACTORS; SPHENOID RIDGE; EN-PLAQUE; RECURRENCE; BENIGN; RADIOTHERAPY AB Object. The authors identified clinical features associated with progression and death in atypical meningioma (AM). Methods. Forty-seven cases of primary AM treated at Massachusetts General Hospital were retrospectively evaluated for clinical features. Associations with progress ion-free survival (PFS) and overall survival were assessed. Results. The estimated median PFS was 56 months (95% CI 35 months-not estimable). The overall 3- and 5-year PFS rates were 65% (95% CI 44-80%) and 48% (95% CI 26-67%), respectively. The median survival time and 5- and 10-year survival rates were 158 months (95% Cl 103 months-not estimable), and 86% (95% CI 69-94%) and 61% (95% CI 35-79%), respectively. Subtotal resection was associated with increased rate of progression compared to gross-total resection (p = 0.05) and trended toward an association with decreased survival (p = 0.09). Bone involvement was associated with an increased rate of disease progression (p = 0.001) and decreased survival (p = 0.04). Bone involvement remained significantly associated with progression after Bonferroni adjustment for multiple comparisons (p = 0.008) and in bivariate Cox regression models. Seventy-eight percent of patients with bone involvement at primary diagnosis had tumor recurrence within bone, whereas only 25% of patients without evidence of bone invasion at primary diagnosis experienced osseous recurrence. Conclusions. Osseous involvement is associated with a poor outcome in patients with AMs bone assessment is therefore extremely important. Further investigation is warranted to assess the effectiveness of bone resection and/or bone-directed radiation therapy in improving outcome. (DOI: 10.3171/2009.2.JNS08877) C1 [Gabeau-Lacet, Darlene; Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Gabeau-Lacet, Darlene; Loeffler, Jay S.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Gabeau-Lacet, Darlene; Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Aghi, Manish; Barker, Fred G.; Louis, David N.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Gabeau-Lacet, D (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM dgabeau@partners.org; dlouis@partners.org FU NIH [T32CA09216] FX Darlene Gabeau-Lacet, M.D., Ph.D., received Support from NIH grant T32CA09216. NR 34 TC 21 Z9 22 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 SEP PY 2009 VL 111 IS 3 BP 464 EP 471 DI 10.3171/2009.2.JNS08877 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 486TW UT WOS:000269223000008 PM 19267533 ER PT J AU Klimo, P Codd, PJ Grier, H Goumnerova, LC AF Klimo, Paul, Jr. Codd, Patrick J. Grier, Holcombe Goumnerova, Liliana C. TI Primary pediatric intraspinal sarcomas SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE pediatric tumor; spine; sarcoma; Ewing sarcoma malignant peripheral nerve sheath tumor ID NERVE-SHEATH TUMOR; PRIMITIVE NEUROECTODERMAL TUMOR; SOFT-TISSUE SARCOMA; EXTRASKELETAL EWINGS-SARCOMA; SPINAL-CORD COMPRESSION; LONG-TERM SURVIVAL; OF-THE-LITERATURE; CAUDA-EQUINA; MALIGNANT SCHWANNOMA; THORACIC SPINE AB Sarcoma, that arise from within the. spinal canal are rare, particularly within the pediatric population In general. these primary intraspinal sarcomas are highly aggressive, posing unique treatment challenges with respect to surgery and choice of adjuvant therapy. The goal must be to obtain the most complete resection possible to minimize the risk of recurrence and metastasis. while preventing potential neurological deficits that may result from aggressive surgery. Among these primary intraspinal Sarcomas are malignant peripheral nerve sheath tumors and members of the Ewing sarcoma family of tumors. The authors present 3 cases of unique spinal sarcomas in children-2 malignant peripheral nerve sheath tumors in patients without neurofibromatosis and in intradural extraosseous Ewing sarcoma arising from the sensory component of a lumbar spinal nerve-and discuss their management and outcome with a review of the current literature. (DOI. 10.3171/2009.3.PEDS08272) C1 [Codd, Patrick J.; Goumnerova, Liliana C.] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Grier, Holcombe] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Neurooncol, Boston, MA 02115 USA. RP Goumnerova, LC (reprint author), Childrens Hosp, Dept Neurosurg, Hunnewell 2,300 Longwood Ave, Boston, MA 02115 USA. NR 87 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 J9 J NEUROS-PEDIATR JI J. Neurosurg.-Pediatr. PD SEP PY 2009 VL 4 IS 3 BP 222 EP 229 DI 10.3171/2009.3.PEDS08272 PG 8 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 486TY UT WOS:000269223300005 PM 19772405 ER PT J AU Kaban, LB Bouchard, C Troulis, MJ AF Kaban, Leonard B. Bouchard, Carl Troulis, Maria J. TI A Protocol for Management of Temporomandibular Joint Ankylosis in Children SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID AUTOGENOUS COSTOCHONDRAL GRAFTS; MANDIBULAR RECONSTRUCTION; RHEUMATIC-DISEASES; GROWTH; DISTRACTION; ARTHROPLASTY; FLAP; CONSTRUCTION; NAVIGATION; CONDYLES C1 [Kaban, Leonard B.; Bouchard, Carl; Troulis, Maria J.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. EM lkaban@partners.org NR 51 TC 63 Z9 65 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2009 VL 67 IS 9 BP 1966 EP 1978 DI 10.1016/j.joms.2009.03.071 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 492YW UT WOS:000269700100026 PM 19686936 ER PT J AU Latremoliere, A Woolf, CJ AF Latremoliere, Alban Woolf, Clifford J. TI Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity SO JOURNAL OF PAIN LA English DT Review DE Central sensitization; inflammatory pain; neuropathic pain; scaffolding protein; heterosynaptic facilitation ID SPINAL DORSAL-HORN; METABOTROPIC GLUTAMATE RECEPTORS; PERIPHERAL-NERVE INJURY; PROTEIN-KINASE-C; SPINOTHALAMIC TRACT NEURONS; LONG-TERM POTENTIATION; D-ASPARTATE RECEPTOR; COMPLETE FREUNDS-ADJUVANT; NITRIC-OXIDE SYNTHASE; GENE-RELATED PEPTIDE AB Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations. Perspective: In this article, we review the major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors. (C) 2009 by the American Pain Society C1 [Woolf, Clifford J.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. EM cwoolf@partners.org FU National Institutes of Health; Fondation pour la Recherche Medicale. FX Supported by the National Institutes of Health and the Fondation pour la Recherche Medicale. NR 405 TC 816 Z9 853 U1 16 U2 154 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD SEP PY 2009 VL 10 IS 9 BP 895 EP 926 DI 10.1016/j.jpain.2009.06.012 PG 32 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 493SY UT WOS:000269759500001 PM 19712899 ER PT J AU Hermsen, JL Gomez, FE Sano, Y Kang, W Maeshima, Y Kudsk, KA AF Hermsen, Joshua L. Gomez, F. Enrique Sano, Yoshifumi Kang, Woodae Maeshima, Yoshinori Kudsk, Kenneth A. TI Parenteral Feeding Depletes Pulmonary Lymphocyte Populations SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article; Proceedings Paper CT National Meeting of Clinical Nutrition Week CY FEB, 2009 CL New Orleans, LA SP A P E N DE parenteral nutrition; T lymphocytes; mucosal immunity; cellular immunity ID ADHESION MOLECULE-1 MADCAM-1; UPPER RESPIRATORY-TRACT; MAJOR ABDOMINAL-TRAUMA; MUCOSAL IMMUNITY; ENTERAL NUTRITION; SEPTIC MORBIDITY; MESSENGER-RNA; ROUTE; EXPRESSION; CELLS AB Background: The effect of parenteral nutrition (PN) on lymphocyte mass in the lung is unknown, but reduced mucosal lymphocytes are hypothesized to play a role in the reduced immunoglobulin A-mediated immunity in both gut and lung. The ability to transfer and track cells between mice may allowed study of diet-induced mucosal immune function. The objectives of this study are to characterize lung T-cell populations following parenteral feeding and to study distribution patterns of transferred donor lung T cells in recipient mice. Methods: In experiment 1, cannulated male Balb/c mice are randomized to receive chow or PN for 5 days. Lung lymphocytes are obtained via collagenase digestion, and flow cytometric analysis is used to identify total T (CD3+) and B (CD45/B220+) cells. In experiment 2, isolated lung T cells from chow-fed male Balb/c mice are pooled and labeled in vitro with a fluorescent dye (carboxyfluorescein diacetate succinimidyl ester [CFSE]), and 1.1 X 10(8) CFSE+ cells (3.1 x 10(6) T cells) are transferred to chow-fed Balb/c recipients. Cells recovered from recipient lungs and intestinal lamina propria (LP) are analyzed by flow cytometry to determine CFSE/CD3+ T cells at 1, 2, and 7 days. In experiment 3, cells are transferred to PN-fed recipients. Results: In experiment 1, PN significantly decreases lung T- and B-cell populations compared with chow feeding. In experiment 2, CFSE+ T-cell retention is highest on day I in lung and LP, and decreases on day 2. Cells are gone by day 7; 98.1% of retained donor lung T cells migrate to recipient lungs and 1.9% to the intestine on day 1. Similar results are seen in experiment 3 after transfer of cells to PN-fed recipients. Conclusions: PN reduces pulmonary lymphocyte populations consistent with impaired respiratory immunity. Transferred lung T cells preferentially localize to recipient lungs rather than intestine with maximal accumulation at 24 hours. Limited cross-talk of transferred lung T cells to the intestine indicates that mucosal lymphocyte traffic might be programmed to localize to specific effector sites. (JPEN J Parenter Enteral, Nutr. 2009;33:535-540) C1 [Hermsen, Joshua L.; Gomez, F. Enrique; Sano, Yoshifumi; Kang, Woodae; Maeshima, Yoshinori; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU NIGMS NIH HHS [R01 GM053439-11, R01 GM053439-08, R01 GM053439-04, R01 GM053439-09, R01 GM053439-07, R01 GM053439-12, R01 GM053439-02, R01 GM053439-06A1, R01 GM053439-03, R01 GM053439-10A2, R01 GM053439, R01 GM053439-05] NR 26 TC 14 Z9 15 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD SEP-OCT PY 2009 VL 33 IS 5 BP 535 EP 540 DI 10.1177/0148607109332909 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 488ZH UT WOS:000269388500007 PM 19556609 ER PT J AU Zella, GC Weinblatt, ME Winter, HS AF Zella, Garrett C. Weinblatt, Michael E. Winter, Harland S. TI Drug-induced Lupus Associated With Infliximab and Adalimumab in an Adolescent With Crohn Disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID NECROSIS-FACTOR-ALPHA; ANTI-TNF-ALPHA; MAINTENANCE INFLIXIMAB; MONOCLONAL-ANTIBODY; PROSPECTIVE COHORT; SHORT-TERM; ERYTHEMATOSUS; EFFICACY; THERAPY; AUTOIMMUNITY C1 [Zella, Garrett C.; Winter, Harland S.] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. [Weinblatt, Michael E.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP Zella, GC (reprint author), Massachusetts Gen Hosp, Dept Pediat, Div Pediat Gastroenterol, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM gzella@partners.org FU Abbott; Amgen; Wyeth; Centocor; UCB FX Dr Zella reports no conflicts of interest; Dr Weinblatt receives grant ;Support from Abbott and Amgen, and provides consultancy for Abbott, Amgen, Wyeth, Centocor, and UCB; and Dr Winter receives clinical research grant support from and provides consultancy for Centocor. NR 34 TC 3 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD SEP PY 2009 VL 49 IS 3 BP 355 EP 358 PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 489CO UT WOS:000269397400015 PM 19516196 ER PT J AU Rebello, G Parikh, R Grottkau, B AF Rebello, Gleeson Parikh, Ravi Grottkau, Brian TI Coaptive Film Versus Subcuticular Suture: Comparing Skin Closure Time Following Identical, Single-session, Bilateral Limb Surgery in Children SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE skin closure technique; bilateral limb surgery AB Background: This study is a randomized controlled trial comparing skin closure time between coaptive film and subcuticular monocryl sutures in children undergoing identical single session, bilateral limb multiple soft tissue releases. Methods: Eight children less than 18 years of age (mean 14.5) with cerebral palsy underwent identical, single session bilateral multiple soft tissue releases in the lower limb from August 2005 to March 2007. There were 50 incisions in all in which 25 incisions were closed with 4-0 intracuticular monocryl sutures and 25 were closed with coaptive film (Steri Strip S; 3M company). Time taken for closure using either technique was recorded. A blinded plastic surgeon used a visual analog scale to assess the cosmetic results at the end of a 3 month follow-up. Results: The average length of incisions closed with coaptive film was almost identical to the corresponding incision on the contralateral limb that was closed with subcuticular monocryl suture (4.45 and 4.81 cm, P = 0.66). The average time for skin closure using monocryl sutures was 167.04 seconds compared with the average time of 79.36 seconds when using coaptive film (P < 0.0001). There was no significant difference in the cosmetic results or the number of wound complications using either technique. Conclusion: Coaptive film is an attractive and cost-effective option for skin closure after pediatric surgery. Clinical Relevance: The time saved, comparable cosmetic results and lack of complications makes coaptive film an attractive option for skin closure in the pediatric age group. C1 [Rebello, Gleeson; Parikh, Ravi; Grottkau, Brian] Massachusetts Gen Hosp, Dept Pediat Orthoped, Boston, MA 02114 USA. RP Rebello, G (reprint author), Massachusetts Gen Hosp Children, Dept Pediat Orthoped, 55 Fruit St,YAW 3400, Boston, MA 02114 USA. EM grebello@partners.org NR 2 TC 5 Z9 5 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 SEP PY 2009 VL 29 IS 6 BP 626 EP 628 PG 3 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 489VN UT WOS:000269451600018 PM 19700995 ER PT J AU Kuban, KCK Allred, EN O'Shea, TM Paneth, N Westra, S Miller, C Rosman, NP Levition, A AF Kuban, Karl C. K. Allred, Elizabeth N. O'Shea, T. Michael Paneth, Nigel Westra, Sjirk Miller, Cindy Rosman, N. Paul Levition, Alan TI Developmental Correlates of Head Circumference at Birth and Two Years in a Cohort of Extremely Low Gestational Age Newborns SO JOURNAL OF PEDIATRICS LA English DT Article ID CRANIAL ULTRASOUND LESIONS; WHITE-MATTER INJURY; CEREBRAL-PALSY; PREMATURE-INFANTS; PRETERM INFANTS; SCHOOL-AGE; POSTNATAL-GROWTH; BRAIN GROWTH; CHILDREN; WEIGHT AB Objectives To evaluate the developmental correlates of microcephaly evident at birth and at 2 years in a cohort born at extremely low gestational age. Methods We assessed development and motor function at 2 years of 958 children born before the 28th week of gestation, comparing those who had microcephaly at birth or 2 years with children with normal head circumference while considering the contribution of neonatal cranial ultrasound lesions. Results A total of 11 % of infants in our sample had microcephaly at 2 years. Microcephaly at 2 years, but not at birth, predicts severe motor and cognitive impairments at 2 years. A total of 71 % of children with congenital microcephaly had a normal head circumference at 2 years and had neurodevelopmental outcomes comparable with those with normal head circumference at birth and 2 years. Among children with microcephaly at 2 years, more than half had a Mental Developmental Index <70, and nearly a third had cerebral palsy. The risks were increased if the child also had cerebral white matter damage on a cranial ultrasound scan obtained 2 years previously. Conclusion Among extremely low gestational age newborns, microcephaly at 2 years, but not at birth, is associated with motor and cognitive impairment at age 2. (J Pediatr 2009;155:344-9). C1 [Kuban, Karl C. K.; Rosman, N. Paul] Boston Univ, Div Pediat Neurol, Dept Pediat, Boston Med Ctr, Boston, MA 02215 USA. [Allred, Elizabeth N.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Allred, Elizabeth N.; Levition, Alan] Childrens Hosp Boston, Neuroepidemiol Unit, Dept Neurol, Boston, MA USA. [Westra, Sjirk] Harvard Univ, Sch Med, Boston, MA USA. [Westra, Sjirk] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Shea, T. Michael] Wake Forest Univ, Dept Pediat, Winston Salem, NC 27109 USA. [Paneth, Nigel] Michigan State Univ, Sparrow Med Ctr, E Lansing, MI 48824 USA. [Miller, Cindy] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Miller, Cindy] Yale Univ, Sch Med, New Haven, CT USA. RP Kuban, KCK (reprint author), 1 Boston Med Ctr Pl,Dowling 3 S, Boston, MA 02118 USA. EM kad.kuban@bmc.org OI Kuban, Karl/0000-0001-5299-3567 FU National Institute of Neurological Disorders and Stroke [1 U01 NS 40069-01 A2] FX Financial support for this research was provided by the National Institute of Neurological Disorders and Stroke (cooperative agreement 1 U01 NS 40069-01 A2). The authors declare no conflicts of interest. NR 40 TC 20 Z9 20 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2009 VL 155 IS 3 BP 344 EP 349 DI 10.1016/j.jpeds.2009.04.002 PG 6 WC Pediatrics SC Pediatrics GA 489NQ UT WOS:000269427400012 PM 19555967 ER PT J AU Colombo, APV Boches, SK Cotton, SL Goodson, JM Kent, R Haffajee, AD Socransky, SS Hasturk, H Van Dyke, TE Dewhirst, F Paster, BJ AF Colombo, Ana Paula V. Boches, Susan K. Cotton, Sean L. Goodson, J. Max Kent, Ralph Haffajee, Anne D. Socransky, Sigmund S. Hasturk, Hatice Van Dyke, Thomas E. Dewhirst, Floyd Paster, Bruce J. TI Comparisons of Subgingival Microbial Profiles of Refractory Periodontitis, Severe Periodontitis, and Periodontal Health Using the Human Oral Microbe Identification Microarray SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Pathogen; periodontitis; subgingival; therapy ID CIGARETTE-SMOKING; LONG-TERM; LAUTROPIA-MIRABILIS; TOOTH LOSS; DISEASE; THERAPY; PATHOGENS; FEATURES; MICROORGANISMS; COMBINATION AB Background: This study compared the subgingival microbiota of subjects with refractory periodontitis (RP) to those in subjects with treatable periodontitis (GRs = good responders) or periodontal health (PH) using the Human Oral Microbe Identification Microarray (HOMIM). Methods: At baseline, subgingival plaque samples were taken from 47 subjects with periodontitis and 20 individuals with PH and analyzed for the presence of 300 species by HOMIM. The subjects with periodontitis were classified as having RP (n = 17) based on mean attachment loss (AL) and/or more than three sites with AL >= 2.5 mm after scaling and root planing, surgery, and systemically administered amoxicillin and metronidazole or as GRs (n = 30) based on mean attachment gain and no sites with AL >= 2.5 mm after treatment. Significant differences in taxa among the groups were sought using the Kruskal-Wallis and chi(2) tests. Results: More species were detected in patients with disease (GR or RP) than in those without disease (PH). Subjects with RP were distinguished from GRs or those with PH by a significantly higher frequency of putative periodontal pathogens, such as Parvimonas micra (previously Peptostreptococcus micros or Micromonas micros), Campylobacter gracilis, Eubacterium nodatum, Selenomonas noxia, Tannerella forsythia (previously T. forsythensis), Porphyromonas gingivalis, Prevotella spp., Treponema spp., and Eikenella corrodens, as well as unusual species (Pseudoramibacter alactolyticus, TM7 spp. oral taxon [OT] 346/356, Bacteroidetes sp. OT 272/274, Solobacterium moorei, Desulfobulbus sp. OT 041, Brevundimonas diminuta, Sphaerocytophaga sp. OT 337, Shuttleworthia satelles, Filifactor alocis, Dialister invisus/pneumosintes, Granulicatella adiacens, Mogibacterium timidum, Veillonella atypica, Mycoplasma salivarium, Synergistes sp. cluster II, and Acidaminococcaceae [G-1] sp. OT 132/150/155/148/135) (P < 0.05). Species that were more prevalent in subjects with PH than in patients with periodontitis included Actinomyces sp. OT 170, Actinomyces spp. cluster 1, Capnocytophaga sputigena, Cardiobacterium hominis, Haemophilus parainfluenzae, Lautropia mirabilis, Propionibacterium propionicum, Rothia dentocariosa/mucilaginosa, and Streptococcus sanguinis (P < 0.05). Conclusion: As determined by HOMIM, patients with RP presented a distinct microbial profile compared to patients in the GR and PH groups. J Periodontol 2009;80:1421-1432. C1 [Colombo, Ana Paula V.] Univ Fed Rio de Janeiro, Inst Microbiol, Dept Med Microbiol, BR-21941902 Rio De Janeiro, Brazil. [Boches, Susan K.; Cotton, Sean L.; Socransky, Sigmund S.; Dewhirst, Floyd; Paster, Bruce J.] Forsyth Inst, Dept Mol Genet, Boston, MA USA. [Goodson, J. Max] Forsyth Inst, Dept Clin Res, Boston, MA USA. [Kent, Ralph] Forsyth Inst, Dept Biostat, Boston, MA USA. [Haffajee, Anne D.] Forsyth Inst, Dept Periodontol, Boston, MA USA. [Hasturk, Hatice; Van Dyke, Thomas E.] Boston Univ, Dept Periodontol & Oral Biol, Goldman Sch Dent Med, Boston, MA 02215 USA. RP Colombo, APV (reprint author), Univ Fed Rio de Janeiro, Inst Microbiol, Dept Med Microbiol, Bloco 1,Lab 12-03,Av Carlos Chagas Filho,373 Cida, BR-21941902 Rio De Janeiro, Brazil. EM apcolombo@micro.ufrj.br RI Inbeb, Inct/K-2317-2013 FU National Institute of Dental and Craniofacial Research; National Institutes of Health, Bethesda, Maryland [DE11443, RR025771]; National Council for Scientific and Technological Development, Brasilia, DF, Brazil FX This work was supported by National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland (grants DE11443 and RR025771), and by the National Council for Scientific and Technological Development, Brasilia, DF, Brazil. Dr. Paster has a patent pending for methods and arrays for identifying human microflora. Drs. Colombo, Boches, Cotton, Goodson, Kent, Haffajee, Socransky, Hasturk, Van Dyke, and Dewhirst report no conflicts of interest related to this study. NR 57 TC 225 Z9 233 U1 5 U2 51 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 EI 1943-3670 J9 J PERIODONTOL JI J. Periodont. PD SEP PY 2009 VL 80 IS 9 BP 1421 EP 1432 DI 10.1902/jop.2009.090185 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 497XM UT WOS:000270098300008 PM 19722792 ER PT J AU Alloy, LB Bender, RE Wagner, CA Whitehouse, WG Abramson, LY Hogan, ME Sylvia, LG Harmon-Jones, E AF Alloy, Lauren B. Bender, Rachel E. Wagner, Clara A. Whitehouse, Wayne G. Abramson, Lyn Y. Hogan, Michael E. Sylvia, Louisa G. Harmon-Jones, Eddie TI Bipolar Spectrum-Substance Use Co-Occurrence: Behavioral Approach System (BAS) Sensitivity and Impulsiveness as Shared Personality Vulnerabilities SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Review DE bipolar spectrum; substance use; behavioral approach system (BAS) sensitivity; impulsiveness ID ABUSE SCREENING-TEST; NATIONAL EPIDEMIOLOGIC SURVEY; BRAIN ELECTRICAL ASYMMETRIES; FRONTAL CORTICAL RESPONSES; MULTIPLE MEDIATOR MODELS; USE DISORDERS; DRUG-ABUSE; MOOD DISORDERS; EEG ASYMMETRY; INVENTORY IDENTIFICATION AB Bipolar disorders and substance use disorders (SUDS) show high co-occurrence. One explanation for this co-occurrence may be common personality vulnerabilities involved in both. The authors tested whether high behavioral approach system (BAS) sensitivity and impulsiveness are shared personality vulnerabilities in bipolar spectrum disorders and substance use problems and their co-occurrence in a longitudinal study of 132 individuals on the bipolar spectrum and 153 control participants. At Time 1, participants completed the Behavioral Inhibition System/BAS Scales and the Impulsive Nonconformity Scale. Substance use problems were assessed via the Michigan Alcoholism Screening Test and the Drug Abuse Screening Test at 4-month intervals for 1 year. Participants with bipolar disorder had higher rates of lifetime SUDS and substance use problems during the follow-up, relative to control participants. In line with hypotheses, higher BAS sensitivity and impulsiveness predicted bipolar status and increased substance use problems prospectively. BAS total, BAS Fun Seeking, and impulsiveness mediated the association between bipolar spectrum status and prospective substance use problems, with impulsiveness as the most important mediator. High BAS sensitivity and impulsiveness may represent shared personality vulnerabilities for both disorders and may partially account for their co-occurrence. C1 [Alloy, Lauren B.; Bender, Rachel E.; Wagner, Clara A.; Whitehouse, Wayne G.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Abramson, Lyn Y.; Hogan, Michael E.] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. [Sylvia, Louisa G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Harmon-Jones, Eddie] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. RP Alloy, LB (reprint author), Temple Univ, Dept Psychol, 1701 N 13th St, Philadelphia, PA 19122 USA. EM lalloy@temple.edu RI Harmon-Jones, Eddie/A-5636-2008 OI Harmon-Jones, Eddie/0000-0003-4771-3043 FU NIMH NIH HHS [MH 52662, MH 52617, MH 77908, R01 MH052617, R01 MH052617-10, R01 MH052662, R01 MH052662-10, R01 MH077908, R01 MH077908-02, R10 MH052617, R10 MH052662] NR 123 TC 32 Z9 32 U1 10 U2 18 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 EI 1939-1315 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD SEP PY 2009 VL 97 IS 3 BP 549 EP 565 DI 10.1037/a0016061 PG 17 WC Psychology, Social SC Psychology GA 488CI UT WOS:000269326300011 PM 19686007 ER PT J AU Hanson, LR Roeytenberg, A Martinez, PM Coppes, VG Sweet, DC Rao, RJ Marti, DL Hoekman, JD Matthews, RB Frey, WH Panter, SS AF Hanson, Leah R. Roeytenberg, Annina Martinez, Paula M. Coppes, Valerie G. Sweet, Donald C. Rao, Reshma J. Marti, Dianne L. Hoekman, John D. Matthews, Rachel B. Frey, William H., II Panter, S. Scott TI Intranasal Deferoxamine Provides Increased Brain Exposure and Significant Protection in Rat Ischemic Stroke SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CEREBRAL-ARTERY OCCLUSION; INSULIN IMPROVES MEMORY; CENTRAL-NERVOUS-SYSTEM; IMPAIRED OLDER-ADULTS; IRON CHELATOR; INTRACEREBRAL HEMORRHAGE; TRANSGENIC MICE; INTERFERON-BETA; FACTOR-I; DESFERRIOXAMINE AB Deferoxamine (DFO) is a high-affinity iron chelator approved by the Food and Drug Administration for treating iron overload. Preclinical research suggests that systemically administered DFO prevents and treats ischemic stroke damage and intracerebral hemorrhage. However, translation into human trials has been limited, probably because of difficulties with DFO administration. A noninvasive method of intranasal administration has emerged recently as a rapid way to bypass the blood-brain barrier and target therapeutic agents to the central nervous system. We report here that intranasal administration targets DFO to the brain and reduces systemic exposure, and that intranasal DFO prevents and treats stroke damage after middle cerebral artery occlusion (MCAO) in rats. A 6-mg dose of DFO resulted in significantly higher DFO concentrations in the brain (0.9-18.5 mu M) at 30 min after intranasal administration than after intravenous administration (0.1-0.5 mu M, p < 0.05). Relative to blood concentration, intranasal delivery increased targeting of DFO to the cortex approximately 200-fold compared with intravenous delivery. Intranasal administration of three 6-mg doses of DFO did not result in clinically significant changes in blood pressure or heart rate. Pretreatment with intranasal DFO (three 6-mg doses) 48 h before MCAO significantly decreased infarct volume by 55% versus control (p < 0.05). In addition, post-treatment with intranasal administration of DFO (six 6-mg doses) immediately after reperfusion significantly decreased infarct volume by 55% (p < 0.05). These experiments suggest that intranasally administered DFO may be a useful treatment for stroke, and a prophylactic for patients at high risk for stroke. C1 [Hanson, Leah R.; Martinez, Paula M.; Sweet, Donald C.; Rao, Reshma J.; Marti, Dianne L.; Hoekman, John D.; Matthews, Rachel B.; Frey, William H., II] Reg Hosp, Alzheimers Res Ctr, HealthPartners Res Fdn, St Paul, MN 55101 USA. [Roeytenberg, Annina; Coppes, Valerie G.; Panter, S. Scott] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Roeytenberg, Annina; Coppes, Valerie G.; Panter, S. Scott] San Francisco VA Med Ctr, Dept Neurosurg, San Francisco, CA USA. RP Hanson, LR (reprint author), Reg Hosp, Alzheimers Res Ctr, HealthPartners Res Fdn, 640 Jackson St, St Paul, MN 55101 USA. EM Leah.R.Hanson@HealthPartners.com OI Frey II, William/0000-0002-6373-0794 FU National Institutes of Health [R21-NS04761401A1]; Alzheimer's Research Center FX This work was supported by the National Institutes of Health [Grant R21-NS04761401A1] and by the Alzheimer's Research Center. NR 39 TC 67 Z9 71 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2009 VL 330 IS 3 BP 679 EP 686 DI 10.1124/jpet.108.149807 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 485SO UT WOS:000269144500002 PM 19509317 ER PT J AU Witt, WP Kahn, R Fortuna, L Winickoff, J Kuhlthau, K Pirraglia, PA Ferris, T AF Witt, Whitney P. Kahn, Robert Fortuna, Lisa Winickoff, Jonathan Kuhlthau, Karen Pirraglia, Paul A. Ferris, Timothy TI Psychological Distress as a Barrier to Preventive Healthcare Among US Women SO JOURNAL OF PRIMARY PREVENTION LA English DT Article DE Psychological distress; Usual source of care; Preventive healthcare; Women's mental health ID 10-YEAR FOLLOW-UP; DEPRESSIVE SYMPTOMS; MEDICAL-CARE; MATERNAL DEPRESSION; NATIONAL-HEALTH; UNITED-STATES; BREAST-CANCER; GENERAL-POPULATION; SCREENING SCALES; SUBSTANCE-ABUSE AB To examine the role of psychological distress in accessing routine periodic health examinations among U. S. women of reproductive age, we examined data on 9,166 women aged 18-49 years from the 1998 National Health Interview Survey. In multivariate regression, women with psychological distress were more likely than non-distressed women to report delayed routine care, not having insurance, and lack of a usual source of care. Among women without a usual source of care, distressed women were more than six and one-half times more likely to delay care compared with non-distressed women. Women with psychological distress report delays in receiving routine care. Editors' Strategic Implications: The findings suggest that, for distressed women in particular, continuity of care is vital in accessing routine care and obtaining timely and effective preventive services. C1 [Witt, Whitney P.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53726 USA. [Kahn, Robert] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. [Fortuna, Lisa] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Winickoff, Jonathan; Kuhlthau, Karen; Ferris, Timothy] Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA 02114 USA. [Pirraglia, Paul A.] Brown Univ, Providence VA Med Ctr, Providence, RI 02908 USA. [Pirraglia, Paul A.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02908 USA. RP Witt, WP (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, 610 N Walnut St,Off 503, Madison, WI 53726 USA. EM wwitt@wisc.edu; robert.kahn@cchmc.org; lisa.fortuna@umassmed.edu; jwinickoff@partners.org; kkuhlthau@partners.org; paul.pirraglia@va.gov; tferris@partners.org FU AHRQ HHS [T32 HS00063] NR 99 TC 9 Z9 9 U1 4 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0278-095X J9 J PRIM PREV JI J. Prim. Prev. PD SEP PY 2009 VL 30 IS 5 BP 531 EP 547 DI 10.1007/s10935-009-0190-z PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 646AG UT WOS:000281506700003 PM 19690962 ER PT J AU Kuzman, MR Medved, V Terzic, J Krainc, D AF Kuzman, Martina Rojnic Medved, Vesna Terzic, Janos Krainc, Dimitri TI Genome-wide expression analysis of peripheral blood identifies candidate biomarkers for schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; Gene expression; Biomarkers; Blood; DAAM2 ID GENE-EXPRESSION; BIPOLAR DISORDER; UP-REGULATION; ASSOCIATION; LYMPHOCYTES; DISCORDANT; LEUKOCYTES; DIAGNOSIS; RECEPTOR AB The aim of this study was to analyze gene expression in blood of patients with newly-diagnosed schizophrenia during their first psychotic episode and subsequent remission. Whole blood samples were obtained from 32 untreated patients presenting with their first psychotic episode suggestive of schizophrenia and 32 age- and gender-matched controls. Using Affymetrix micoarrays, we identified significantly altered expression of 180 gene probes in psychotic patients compared to controls. A subset of four significantly changed genes was further confirmed with QRT-PCR. The following genes were significantly altered in patients: glucose transporter, SLC2A3 (p < 0.001) and actin assembly factor DAAM2 (p < 0,001) were increased, whereas translation, zinc metallopeptidase, neurolysin 1 and myosin C were significantly decreased (p < 0.05). Expression of these candidate markers was also analyzed in a longitudinal study (12-24 months) in 12 patients who achieved full remission. Interestingly. expression of DAAM2 returned to control levels in patients who were in remission after their first psychotic episode, suggesting that its expression correlates with diseases progression and/or response to treatment. In summary, we identified changes of gene expression from peripheral blood which might help discriminate patients with schizophrenia from controls. While these results are promising, especially for DAAM2 whose polymorphic variants have been found significantly associated with schizophrenia, it will be important to analyze larger cohorts of patients in order to firmly establish changes in gene expression as blood markers of schizophrenia. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Kuzman, Martina Rojnic; Medved, Vesna] Zagreb Univ Hosp Ctr, Dept Psychiat, Zagreb 10000, Croatia. [Kuzman, Martina Rojnic; Medved, Vesna] Zagreb Sch Med, Zagreb 10000, Croatia. [Terzic, Janos] Univ Split, Split Med Sch, Dept Immunol, Split 21000, Croatia. [Krainc, Dimitri] Harvard Univ, Sch Med, Boston, MA 02109 USA. [Krainc, Dimitri] Massachusetts Gen Hosp, Boston, MA 02109 USA. [Krainc, Dimitri] Mediterranean Inst Life Sci, Split 21000, Croatia. RP Kuzman, MR (reprint author), Zagreb Univ Hosp Ctr, Dept Psychiat, Kispaticeva 12, Zagreb 10000, Croatia. EM mrojnic@gmail.com NR 30 TC 33 Z9 34 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD SEP PY 2009 VL 43 IS 13 BP 1073 EP 1077 DI 10.1016/j.jpsychires.2009.03.005 PG 5 WC Psychiatry SC Psychiatry GA 504NP UT WOS:000270624000003 PM 19358997 ER PT J AU Stewart, SE Stack, DE Tsilker, S Alosso, J Stephansky, M Hezel, DM Jenike, EA Haddad, SA Kant, J Jenike, MA AF Stewart, S. Evelyn Stack, Denise Egan Tsilker, Svetlana Alosso, Jen Stephansky, Matt Hezel, Dianne M. Jenike, Eric A. Haddad, Stephen A. Kant, Jared Jenike, Michael A. TI Long-term outcome following Intensive Residential Treatment of Obsessive-Compulsive Disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Obsessive-Compulsive Disorder; Intensive Residential Treatment; Long-term outcome; Inpatient; Effectiveness ID PLACEBO-CONTROLLED TRIAL; RITUAL PREVENTION; COGNITIVE THERAPY; BEHAVIOR-THERAPY; DOUBLE-BLIND; EXPOSURE; RELAPSE; CLOMIPRAMINE; COMBINATION; MULTICENTER AB Background: IRT has been demonstrated as an effective treatment for severe, refractory OCD. Methods: Consecutive IRT subjects were ascertained over a 12 month period (female N = 26, male N = 35). Psychometric measures were completed at admission and discharge. from the McLean/MGH OCD Institute IRT, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beek Depression Inventory (BDI) and the Work and Social Adjustment Scale (WSA)(N = 61). These measures were repeated at one (N = 57), three (N = 42) and six months (N = 36) following discharge. This study was IRB approved. Results: OCD mean severity did not significantly worsen from discharge to the one (17.4, SD 6.5), three (116.5, SD 7.4) or six month (16.2, SD 7.3) follow-up (p > 0.25). Furthermore. the significant improvement from admission was maintained at each of the one (17.4, SD 6.5), three (16.5, SD 7.4) and six month (16.2, SD SD 7.3) follow-up time points (p < 0.001). Relapsers were significantly more likely to be living alone following discharge (p = 0.01), and were less likely to have comorbid illnesses (p = 0.02). There were no significant differences found between study dropouts and completers with regards to YBOCS scores (P > 0.47). Conclusion: In the first OCD IRT long-term follow-up study to date, findings have indicated that mean treatment gains were maintained at one, three, and six months post-discharge. This finding is important as it suggests that improvements of OCD severity were subsequently retained in home and work environments. Improvement of depression severity from admission was also maintained. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Stewart, S. Evelyn; Hezel, Dianne M.; Jenike, Eric A.; Haddad, Stephen A.; Kant, Jared; Jenike, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stewart, S. Evelyn; Stack, Denise Egan; Tsilker, Svetlana; Alosso, Jen; Stephansky, Matt; Hezel, Dianne M.; Jenike, Eric A.; Jenike, Michael A.] McLean Hosp, Obsess Compuls Disorder Inst, Belmont, MA 02178 USA. [Stewart, S. Evelyn; Jenike, Michael A.] Harvard Univ, Sch Med, Boston, MA USA. RP Stewart, SE (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,PNGU,6th Floor, Boston, MA 02114 USA. EM stewart@pngu.mgh.harvard.edu RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 NR 31 TC 7 Z9 7 U1 2 U2 8 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 SEP PY 2009 VL 43 IS 13 BP 1118 EP 1123 DI 10.1016/j.jpsychires.2009.03.012 PG 6 WC Psychiatry SC Psychiatry GA 504NP UT WOS:000270624000009 PM 19419736 ER PT J AU Holland, JM Neimeyer, RA Boelen, PA Prigerson, HG AF Holland, Jason M. Neimeyer, Robert A. Boelen, Paul A. Prigerson, Holly G. TI The Underlying Structure of Grief: A Taxometric Investigation of Prolonged and Normal Reactions to Loss SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Complicated grief; Prolonged grief disorder; Bereavement; Death and dying; Taxometric method ID BEREAVEMENT-RELATED DEPRESSION; COMPLICATED GRIEF; TRAUMATIC GRIEF; DISORDER DISTINCT; ANXIETY; HEALTH; RISK; PSYCHOPATHOLOGY; INTERVENTIONS; REPLICATION AB Recent studies have supported the distinctiveness of complicated and prolonged forms of grief as a cluster of symptoms that is separate from other psychiatric disorders. The distinction between prolonged and normal reactions to loss remains unclear, however, with some believing that prolonged grief represents a qualitatively distinct clinical entity and others conceptualizing it as the extreme end of a continuum. Thus, in this study a taxometric methodology was used to examine the underlying structure of grief. Participants included 1,069 bereaved individuals who had lost a first-degree relative. Each participant completed the Dutch version of the Inventory of Complicated Grief-Revised, which was used to create indicators of prolonged grief. The mean above and mean below a cut (MAMBAC) and maximum eigenvalue (MAXEIG) tests supported a dimensional conceptualization, indicating that pathological reactions might be best defined by the severity of grief symptoms rather than the presence or absence of specific symptoms. C1 [Holland, Jason M.] Stanford Univ, Med Ctr, VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Neimeyer, Robert A.] Univ Memphis, Memphis, TN 38152 USA. [Boelen, Paul A.] Univ Utrecht, Utrecht, Netherlands. [Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Prigerson, Holly G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Holland, JM (reprint author), Stanford Univ, Med Ctr, VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd 152-MPD, Menlo Pk, CA 94025 USA. EM jmhollnd@gmail.com RI Holland, Jason/D-4153-2012 OI Holland, Jason/0000-0002-7849-0762 NR 48 TC 39 Z9 40 U1 3 U2 18 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD SEP PY 2009 VL 31 IS 3 BP 190 EP 201 DI 10.1007/s10862-008-9113-1 PG 12 WC Psychology, Clinical SC Psychology GA 464XA UT WOS:000267541700006 ER PT J AU Osman, A Williams, JE Espenschade, K Gutierrez, PM Bailey, JR Chowdhry, O AF Osman, Augustine Williams, John E. Espenschade, Kelly Gutierrez, Peter M. Bailey, Jennifer R. Chowdhry, Osman TI Further Evidence of the Reliability and Validity of the Multidimensional Anxiety SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Self-reported anxiety; Youth; Multidimensional anxiety scale; Psychometrics ID ADOLESCENT PSYCHIATRIC-INPATIENTS; DEPRESSION INVENTORY-II; BECK HOPELESSNESS SCALE; PSYCHOMETRIC PROPERTIES; NEGATIVE AFFECTIVITY; SCORE RELIABILITY; TRIPARTITE MODEL; CHILDREN MASC; SYMPTOMS; CONSTRUCTS AB The psychometric properties of the Multidimensional Anxiety Scale for Children (MASC) were examined in adolescent psychiatric inpatient samples. In Study 1 (n = 287), confirmatory factor analyses provided satisfactory fit for the four-factor (comparative fit index; CFI = 0.856) and higher-order (CFI = 0.854) solutions. Using parcels as items, the fit of the four-factor model was improved substantially (CFI = 0.935). Next, in the bifactor analyses, support was attained for a model that included a general factor and four domain specific subfactors. In Study 2 (n = 195 inpatient youths), the MASC showed good scale reliability and concurrent validity. Results of the receiver operating characteristic curve and binary logistic regression analyses provided adequate evidence for discriminative validity. In Study 3 (n = 40), test-retest reliability of scores on the MASC-10 scale over a 3-week period was adequate (r (tt) = 0.83, p < 0.001) for children ages 8 to 11 years. C1 [Osman, Augustine] Univ Texas San Antonio, Dept Psychol, San Antonio, TX 78249 USA. [Williams, John E.; Espenschade, Kelly; Chowdhry, Osman] Univ No Iowa, Cedar Falls, IA 50614 USA. [Gutierrez, Peter M.] Denver VA Med Ctr, VISN MIRECC 19, Denver, CO USA. [Bailey, Jennifer R.] Univ Mississippi, Oxford, MS USA. RP Osman, A (reprint author), Univ Texas San Antonio, Dept Psychol, 1 UTSA Circle, San Antonio, TX 78249 USA. EM augustine.osman@utsa.edu NR 69 TC 6 Z9 6 U1 1 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD SEP PY 2009 VL 31 IS 3 BP 202 EP 214 DI 10.1007/s10862-008-9095-z PG 13 WC Psychology, Clinical SC Psychology GA 464XA UT WOS:000267541700007 ER PT J AU Buffum, MD Buccheri, R Trygstad, L Gerlock, AA Birmingham, P Dowling, GA Kuhlman, GJ AF Buffum, Martha D. Buccheri, Robin Trygstad, Louise Gerlock, April A. Birmingham, Patricia Dowling, Glenna A. Kuhlman, Gloria J. TI Behavioral Management of AUDITORY HALLUCINATIONS Implementation and Evaluation of a 10-Week Course SO JOURNAL OF PSYCHOSOCIAL NURSING AND MENTAL HEALTH SERVICES LA English DT Article ID SCHIZOPHRENIA AB A 10-session behavioral course for self-management of auditory hallucinations in,patients with schizophrenia has demonstrated positive outcomes. This article evaluates both the course's implementation and benefits to patients attending the course. Teleconferencing, electronic media, and 26 monthly conference calls were used to educate six advanced practice nurses (APNs) at six sites about the course implementation. Thirty-two patients; within the U.S. Department of Veterans Affairs participated in the course. All of the APNs reported course helpfulness, improved communication with patients about voices, and improved harm assessment. Of the patients, 96% found the course helpful: 67% no longer heard voices to harm self or others, and 60% had improved auditory hallucination intensity scores. The project demonstrated successful implementation and practice integration with APNs' activities corresponding to Rogers' stages of innovation adoption. Facilitators and barriers to implementation are also described. C1 [Buffum, Martha D.; Birmingham, Patricia] VA Med Ctr, San Francisco, CA USA. [Buccheri, Robin; Trygstad, Louise] Univ San Francisco, Sch Nursing, San Francisco, CA 94117 USA. [Dowling, Glenna A.] Univ San Francisco, Dept Physiol Nursing, San Francisco, CA 94117 USA. [Gerlock, April A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Gerlock, April A.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Kuhlman, Gloria J.] VA Palo Alto Hlth Care Syst, Menlo Pk Div, Menlo Pk, CA USA. RP Buffum, MD (reprint author), VA Med Ctr 118, 4150 Clement St, San Francisco, CA 94121 USA. EM Martha.Buffum@va.gov FU University of San Francisco Faculty Development Funds FX The authors disclose that they have no significant financial interests in any product or class of products discussed directly or indirectly in this activity. This material is the result of work supported with resources and the use of facilities at VA Medical Center, San Francisco, California; VA Puget Sound, Seattle, Washington; and VA Palo Alto Health Care System, Palo Alto, California. This project was funded by a grant from University of San Francisco Faculty Development Funds. NR 11 TC 9 Z9 9 U1 0 U2 7 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0279-3695 J9 J PSYCHOSOC NURS JI J. Psychosoc. Nurs. Ment. Health Serv. PD SEP PY 2009 VL 47 IS 9 BP 32 EP 40 DI 10.3928/02793695-20090730-01 PG 9 WC Nursing SC Nursing GA 494JW UT WOS:000269809900011 PM 19772249 ER PT J AU Ang, DC Tahir, N Hanif, H Tong, Y Ibrahim, SA AF Ang, Dennis C. Tahir, Nighat Hanif, Hufza Tong, Yan Ibrahim, Said A. TI African Americans and Whites Are Equally Appropriate to be Considered for Total Joint Arthroplasty SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE RACIAL DISPARITY; TOTAL JOINT ARTHROPLASTY; CLINICAL APPROPRIATENESS ID CORONARY REVASCULARIZATION PROCEDURES; SELF-RATED HEALTH; ETHNIC DISPARITIES; EXPLICIT CRITERIA; COMORBIDITY INDEX; KNEE OSTEOARTHRITIS; PATIENT PREFERENCES; RACIAL DISPARITIES; HIP; REPLACEMENT AB Objective. Ethnic disparities in the use of total joint arthroplasty (TJA) may be attributed to differences in the clinical appropriateness to undergo TJA. We Sought to determine if racial differences in clinical appropriateness for surgery existed among a sample of primary care clinic patients with moderately to severely symptomatic knee or hip osteoarthritis (OA). Methods. We used the cross-sectional data of 684 patients who are potential candidates for TJA. Using a validated TJA appropriateness algorithm, ail appropriateness factor was derived using the following variables: age (50-70 or >70 yrs), Charlson comorbidity (<= 1 or >1), Western Ontario and McMaster Universities OA Index (WOMAC) pain and physical function, and adequacy of previous medical management. We used logistic regression to estimate the association of race with the dichotomous outcome of clinical appropriateness for TJA consideration. Results. Sample consisted of 425 (62%) whites and 260 (38%) African Americans; 532 (78%) had knee OA and 153 (22%) had hip OA. The mean age was 64 +/- 9 years and the mean body mass index was 33.6 +/- 8 kg/m(2). The mean overall WOMAC score was 56 +/- 14 (range 30-96), suggesting modesty erately severe OA. There were no significant racial group differences (p=0.3) in the proportions of those deemed clinically appropriate for TJA. After controlling for potential confounders, race was not a predictor of clinical appropriateness for TJA (odds ratio 1.2, 95% confidence interval 0.8-1.8, p=0.3). Conclusion. African Americans and whites were equally appropriate to be considered for TJA. (First Release July 15 2009: J Rheumatol 2009;36:1971-6; doi: 10.3899/jrheum.081214) C1 [Ang, Dennis C.; Tahir, Nighat; Hanif, Hufza] Indiana Univ, Sch Med, Dept Med, Div Rheumatol, Indianapolis, IN 46202 USA. [Ibrahim, Said A.] Univ Pittsburgh, Dept Med, Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst,Div Internal Med, Pittsburgh, PA USA. [Tong, Yan] Indiana Univ, Sch Med, Dept Med, Div Biostat, Indianapolis, IN 46202 USA. RP Ang, DC (reprint author), Indiana Univ, Sch Med, Dept Med, Div Rheumatol, 1110 W Michigan St,Room 545, Indianapolis, IN 46202 USA. EM dang@iupui.edu FU National Center for Research Resources (NCRR) [PR017725]; National Institutes of Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24AR055259] FX Dr. Ang is supported in part by a Mentored Patient-Oriented Career Development Award (PR017725) from the National Center for Research Resources (NCRR), National Institutes of Health. Dr Ibrahim is supported by grant no. K24AR055259 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. NR 48 TC 9 Z9 9 U1 2 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 2009 VL 36 IS 9 BP 1971 EP 1976 DI 10.3899/jrheum.081214 PG 6 WC Rheumatology SC Rheumatology GA 492RT UT WOS:000269677600024 PM 19605675 ER PT J AU Rosen, R Shifren, J Monz, B Odom, D Russo, P Johannes, C AF Rosen, Raymond Shifren, Jan Monz, Brigitta Odom, Dawn Russo, Patricia Johannes, Catherine TI THE PREDICTORS OF SEXUAL DISTRESS IN WOMEN WITH LOW SEXUAL DESIRE SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [Johannes, Catherine] RTI Hlth Solut, Waltham, MA USA. [Rosen, Raymond] New England Res Inst, Watertown, MA 02172 USA. [Shifren, Jan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Monz, Brigitta] Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany. [Odom, Dawn] RTI Hlth Solut, Res Triangle Pk, NC USA. [Russo, Patricia] PRC Hlth Serv Res & Management Consulting, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD SEP PY 2009 VL 6 BP 370 EP 370 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 490MO UT WOS:000269505300016 ER PT J AU Choi, JC Bakaeen, FG Huh, J Dao, TK LeMaire, SA Coselli, JS Chu, D AF Choi, Justin C. Bakaeen, Faisal G. Huh, Joseph Dao, Tam K. LeMaire, Scott A. Coselli, Joseph S. Chu, Danny TI Outcomes of Coronary Surgery at a Veterans Affairs Hospital Versus Other Hospitals SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 4th Academic Surgical Congress CY 2009 CL Ft Myers, FL DE CABG; outcomes; veterans affairs ID PRIVATE-SECTOR HOSPITALS; CARDIAC-SURGERY; HEALTH-CARE; IMPROVEMENT; MORTALITY; QUALITY AB Background. The aim of this study was to compare outcomes of coronary artery bypass grafting (CABG) operations at a VA hospital and non-VA hospitals. Materials and Methods. Using the 2004 Nationwide Inpatient Sample database, we identified 48,669 discharge records of patients who underwent CABG in non-VA hospitals and compared these patients' outcomes with those of 688 patients who underwent CABG at our VA hospital from 2002 to 2006. Student t- tests and chi(2) tests were used to identify significant intergroup differences. Results. The VA patients were slightly younger than the non-VA patients (62 +/- 8 versus 66 +/- 11 y, P < 0.0001). The VA patients also had a higher prevalence of prior myocardial infarction (60.6% versus 34.6%), congestive heart failure (38.2% versus 22.1%), peripheral vascular disease (25.9% versus 7.2%), cerebral vascular disease (23.4% versus 5.9%), chronic obstructive pulmonary disease (32.3% versus 16.6%), and diabetes (41.7% versus 29.7%) (P < 0.0001 for all). Nonetheless, the in-hospital mortality rate was significantly lower in VA patients than in non-VA patients (1.6% versus 3.0%, P = 0.03). Conclusions. Despite the higher prevalence of comorbidities, patients who underwent CABG at a VA hospital had a significantly lower mortality rate than CABG patients in non-VA hospitals. Published by Elsevier Inc. All rights reserved. C1 [Chu, Danny] Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, Houston, TX 77030 USA. [Choi, Justin C.; Bakaeen, Faisal G.; Huh, Joseph; LeMaire, Scott A.; Coselli, Joseph S.; Chu, Danny] Baylor Coll Med, Houston, TX 77030 USA. [Bakaeen, Faisal G.; Huh, Joseph; LeMaire, Scott A.; Coselli, Joseph S.; Chu, Danny] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA. [Dao, Tam K.] Univ Houston, Houston, TX USA. RP Chu, D (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM dchumd@gmail.com NR 16 TC 7 Z9 7 U1 0 U2 2 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 SEP PY 2009 VL 156 IS 1 BP 150 EP 154 DI 10.1016/j.jss.2009.03.041 PG 5 WC Surgery SC Surgery GA 491UT UT WOS:000269606300026 PM 19577261 ER PT J AU Bakaeen, FG Chu, D Chi, C Lin, PH Kougias, P Hawes, L LeMaire, SA Coselli, JS Huh, J AF Bakaeen, Faisal G. Chu, Danny Chi, Casiano Lin, Peter H. Kougias, Panagiotis Hawes, Luke LeMaire, Scott A. Coselli, Joseph S. Huh, Joseph TI Cardiac Surgery in Patients with Major Lower Extremity Amputation: A Single Institution Experience SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 4th Academic Surgical Congress CY 2009 CL Ft Myers, FL DE cardiac surgery; aortic valve replacement; coronary artery bypass grafting; amputee; rehabilitation; physical therapy ID LOWER-LIMB AMPUTATION; REHABILITATION; GUIDELINES AB Background. Cardiac surgery patients with lower-extremity amputations pose a challenge in terms of medical comorbidities and functional recovery. Methods. A retrospective review of all patients (n = 10) with preexisting below-knee amputation (BKA) or more proximal amputation level who underwent cardiac surgery between April 1998 and April 2008. Data were analyzed to evaluate outcomes. Results. The median age was 59 y (range, 51-75 y). One patient had bilateral above-knee amputation (AKA), and 9 had BKAs (two bilateral). Comorbidities included diabetes (n = 5), peripheral vascular disease (n = 7), cerebrovascular disease (n = 2), hypertension (n = 9), chronic renal insufficiency (n = 2), pulmonary hypertension (n = 1), and pulmonary fibrosis (n = 1). Nine patients underwent coronary artery bypass grafting and one patient underwent aortic valve replacement. There were no operative deaths. The median length of hospital stay (to home discharge) was 12.5 d (range, 5-562 d). Eight patients were transferred to a rehabilitation unit or a chronic care facility before being discharged to home. At follow-up (median, 1.5 y; range, 0.4-3.8 y), all but one patient were alive and ha returned to their preoperative ambulatory status. Conclusions. In our experience, patients with lower-extremity amputations require prolonged hospitalization after cardiac surgery but can expect good midterm outcomes and functional recovery. Published by Elsevier Inc. All rights reserved. C1 [Bakaeen, Faisal G.] St Lukes Episcopal Hosp, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Baylor Coll Med,Dept Cardiothorac Surg, Houston, TX 77030 USA. RP Bakaeen, FG (reprint author), St Lukes Episcopal Hosp, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Baylor Coll Med,Dept Cardiothorac Surg, OCL 112 2002 Holcombe Blvd, Houston, TX 77030 USA. EM fbakaeen@bcm.edu NR 7 TC 1 Z9 1 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2009 VL 156 IS 1 BP 161 EP 166 DI 10.1016/j.jss.2009.03.039 PG 6 WC Surgery SC Surgery GA 491UT UT WOS:000269606300028 PM 19552921 ER PT J AU Hua, LW AF Hua, Liwei TI Me, Myself, and Them: A Firsthand Account of One Young Person's Experience With Schizophrenia SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Hua, Liwei] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hua, LW (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM llhua@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2009 VL 48 IS 9 BP 958 EP 959 DI 10.1097/01.chi.0000356619.93143.98 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 488AW UT WOS:000269322300014 ER PT J AU Makredes, M Robinson, D Bala, M Kimball, AB AF Makredes, Maryanne Robinson, Don, Jr. Bala, Mohan Kimball, Alexa B. TI The burden of autoimmune disease: A comparison of prevalence ratios in patients with psoriatic arthritis and psoriasis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT International Investigative Dermatology Meeting CY MAY 12-17, 2008 CL Kyoto, JAPAN SP Japanese Soc Investigat Dermatol, Soc Investigat Dermatol, European Soc Dermatol Res, Federat Pharmaceut Manufactures Assoc Japan, Galderma, Janssen Pharmaceut KK, Maruho Co Ltd, Sanofi Aventis KK, Torii Pharmaceut Co Ltd, Abbott Japan Co Ltd, CERIES, Chanel, Clin Labs KK, Dainippon Sumitomo Pharma, Eisai Co Ltd, GlaxoSmithKline KK, Kyowa Hakko Kogyo Co Ltd, Mitsubishi Tanabe Pharma Corp, Nippon Boehringer Ingelheim, Novartis Pharma KK, Schering Plough, Shionogi & Co Ltd, Shiseido Co Ltd, Japan Cosmet Ind Assoc, Igaku Shoin, Pierre Fabre Japan Co Ltd DE autoimmune disease; psoriasis; psoriatic arthritis ID INFLAMMATORY-BOWEL-DISEASE; RISK-FACTORS; COMORBIDITIES; DATABASES; SKIN AB Background: Current research has confirmed that many inflammatory autoimmune (AI) diseases are due to derangements in multiple cytokine pathways. Some of these cytokines appear to play comparable key roles across diseases, suggesting that a similar underlying systemic inflammatory cascade Could be responsible for various disease states. A recent study Supports the hypothesis of a common cytokine-based pathology by showing that having one AI disease significantly increased the risk of having another AI disease. Psoriasis is an AI, manifesting as a chronic inflammatory skin condition and is clearly associated with other conditions, most obviously psoriatic arthritis (PsA). Objective. We sought to examine whether patients with PsA enrolled in managed health care plans carry a higher AI disease burden than Patients with cutaneous psoriasis only (PsO). Methods: Patients 18 years or older enrolled in a health claims database were classified by two clinical subtypes: PsA and PsO. Control Subjects were matched 3:1 to patients with psoriasis on age, sex, census region, and length of previous medical insurance coverage. AI disease diagnoses were identified through International Classification of Diseases, Ninth Revision, codes. The association of other AI diseases with each psoriasis cohort was assessed using a prevalence ratio. Results: PsO was associated with a higher prevalence ratio for the 3 gastrointestinal diseases: Crohn disease (1.6 [confidence interval {CI} 1.4-2.0]), ulcerative colitis (1.3 [CI 1.1-1.6]), and inflammatory bowel disease (1.4 [CI 1.2-1.6]). PsA was also associated with a higher prevalence ratio for the gastrointestinal diseases: Crohn disease (2.1 [CI 1.3-3.3]), ulcerative colitis (2.0 [CI 1.3-3.1]), and inflammatory bowel disease (1.8 [CI 1.3-2.5]). Patients with PsA had an increased prevalence ratio associated with giant cell arteritis (4.8 [CI 1.5-15.7]) and Pulmonary fibrosis (1.9 [CI 1.2-3.0]). Limitations: Detection and misclassification biases may have affected these findings. Conclusions. These findings support the hypothesis that PsA and PsO are associated with development of other AI diseases. The data suggest that evaluating patients with psoriasis for other associated disorders in a prospective manner may be important, because they may be more likely to experience the onset of another AI disease. Treatment planning for these patients could, therefore, require the medical management of more than one AI disease. Further, our data Suggest that PsA and PsO may be divergent in ways previously not described that could inform future research. (J Am Acad Dermatol 2009;61:405-10.) C1 [Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials Skin, Boston, MA 02115 USA. [Robinson, Don, Jr.] Johnson & Johnson Pharmaceut Serv, Malvern, PA USA. [Bala, Mohan] GlaxoSmithKline Inc, Collegeville, PA USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials Skin, 50 Staniford St,240, Boston, MA 02115 USA. EM harvardskinstudies@partners.org NR 25 TC 26 Z9 26 U1 0 U2 1 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 SEP PY 2009 VL 61 IS 3 BP 405 EP 410 DI 10.1016/j.jaad.2009.02.015 PG 6 WC Dermatology SC Dermatology GA 489JF UT WOS:000269415700003 PM 19700012 ER PT J AU Brandolini, J Gentile, S Pina, F Jarrell, DM AF Brandolini, J. Gentile, S. Pina, F. Jarrell, D. M. TI Standardizing the Definition of a "Dirty" Soiled Rodent Cage SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Brandolini, J.; Gentile, S.; Pina, F.; Jarrell, D. M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 541 EP 541 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000041 ER PT J AU Camacho, JN Schultz, C AF Camacho, J. N. Schultz, C. TI A Rational Approach to Enriched Nutrition for Nonhuman Primates SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Camacho, J. N.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Schultz, C.] Land OLakes Purina Feed, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 543 EP 543 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000048 ER PT J AU Young, SH Smith, A O'Day, TE AF Young, S. H. Smith, A. O'Day, T. E. TI A Novel Ergonomic Procedure Cart SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Young, S. H.; Smith, A.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [O'Day, T. E.] Partners HealthCare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 548 EP 548 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000064 ER PT J AU Camacho, JN Moeller, E Morris, J AF Camacho, J. N. Moeller, E. Morris, J. TI A Psychologic Wellbeing Response Plan for Nonhuman Primates SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Camacho, J. N.; Moeller, E.; Morris, J.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 558 EP 558 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000093 ER PT J AU Luboyeski, S AF Luboyeski, S. TI Benefit of Decreasing Noise Stimulation for Anesthetized Nonhuman Primates Undergoing Magnetic Resonance Imaging Scans SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Luboyeski, S.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 558 EP 558 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000094 ER PT J AU Smith, A Luboyeski, S AF Smith, A. Luboyeski, S. TI A Novel Warming Device for Animal Anesthesia Recovery SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Smith, A.; Luboyeski, S.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 558 EP 559 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000095 ER PT J AU Ingram, LA Morris, J Moeller, E AF Ingram, L. A. Morris, J. Moeller, E. TI Continued Improvement of Rodent Health Problem Identification and Resolution SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Ingram, L. A.; Morris, J.; Moeller, E.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 576 EP 576 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000156 ER PT J AU Hurley, A Gibson, R Hurley, RJ Hurley, J AF Hurley, A. Gibson, R. Hurley, R. J. Hurley, J. TI Specific Pathogen-Free Sheep Monitoring and Biosecurity SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Hurley, A.; Gibson, R.] Univ New Hampshire, New Hampshire Vet Diagnost Lab, Durham, NH 03824 USA. [Hurley, R. J.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Hurley, A.; Hurley, R. J.; Hurley, J.] New England Ovis LLC, Rollinsford, NH USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 584 EP 584 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000182 ER PT J AU Teixeira, L Smith, A AF Teixeira, L. Smith, A. TI Optimizing Water Bottle Location for Nonhuman Primate Caging SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Teixeira, L.; Smith, A.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 607 EP 608 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000261 ER PT J AU Young, SH AF Young, S. H. TI Reducing Bedding Dispenser Defects SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Young, S. H.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 608 EP 608 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000262 ER PT J AU Beckman, W Hickman, DL Thompson, K DenHerder, J Gallagher, J AF Beckman, W. Hickman, D. L. Thompson, K. DenHerder, J. Gallagher, J. TI Enrichment: A Technician's Point of View SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Beckman, W.; Hickman, D. L.; Thompson, K.; DenHerder, J.; Gallagher, J.] Portland VA Med Ctr, VMU, Portland, OR USA. [Hickman, D. L.] IUPUI, LARC, Indianapolis, IN USA. RI Hickman, Debra/D-3289-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 609 EP 610 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000268 ER PT J AU Beckman, W DenHerder, J Thompson, K Hickman, DL AF Beckman, W. DenHerder, J. Thompson, K. Hickman, D. L. TI Technical Services Offered by the Veterinary Medical Unit SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Beckman, W.; DenHerder, J.; Thompson, K.; Hickman, D. L.] Portland VA Med Ctr, VMU, Portland, OR USA. [Hickman, D. L.] IUPUI, LARC, Indianapolis, IN USA. RI Hickman, Debra/D-3289-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 610 EP 610 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000269 ER PT J AU Beckman, W Thompson, K DenHerder, J Hickman, DL AF Beckman, W. Thompson, K. DenHerder, J. Hickman, D. L. TI The Amazing and Monogamous Prairie Vole (Microtus ochrogaster) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Beckman, W.; Thompson, K.; DenHerder, J.; Hickman, D. L.] Portland VA Med Ctr, VMU, Portland, OR USA. [Hickman, D. L.] IUPUI, LARC, Indianapolis, IN USA. RI Hickman, Debra/D-3289-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 610 EP 610 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000270 ER PT J AU Castranova, DA Lawrence, C Lawton, A Doherty, A Baumann, D Wang, C Wilson, C Ramos, J Best, J Adatto, I Weinstein, BM AF Castranova, D. A. Lawrence, C. Lawton, A. Doherty, A. Baumann, D. Wang, C. Wilson, C. Ramos, J. Best, J. Adatto, I. Weinstein, B. M. TI The Effects of Tank Density on Reproductive Performance in Zebrafish SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Castranova, D. A.; Wang, C.; Weinstein, B. M.] NICHD, Mol Genet Lab, NIH, Bethesda, MD USA. [Castranova, D. A.; Wang, C.] Charles River Labs, Germantown, MD USA. [Lawton, A.] Univ Queensland, Brisbane, Qld 4072, Australia. [Lawrence, C.; Best, J.; Adatto, I.] Childrens Hosp Boston, Boston, MA USA. [Wilson, C.] Univ Coll, London, England. [Doherty, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ramos, J.] Barcelona Biomed Res Pk, Barcelona, Spain. [Baumann, D.] Stowers Inst Med Res, Kansas City, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 614 EP 614 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000283 ER PT J AU Whary, MT Shi, H Taylor, NS Ge, Z Feng, Y Lofgren, JL Muthupalani, S Wang, TC Fox, JG AF Whary, M. T. Shi, H. Taylor, N. S. Ge, Z. Feng, Y. Lofgren, J. L. Muthupalani, S. Wang, T. C. Fox, J. G. TI Coinfection with the Nematode Heligmosomoides polygyrus Reduces Intestinal Metaplasia and Dysplasia in the INS-GAS Mouse Model of Helicobacter pylori-Associated Gastric Cancer SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Whary, M. T.; Taylor, N. S.; Ge, Z.; Feng, Y.; Lofgren, J. L.; Muthupalani, S.; Fox, J. G.] MIT, Mucosal Immunol Lab, Cambridge, MA 02114 USA. [Shi, H.] Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Wang, T. C.] Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 629 EP 630 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000329 ER PT J AU Huang, P Kozin, SV Gerweck, LE Suit, HD AF Huang, P. Kozin, S. V. Gerweck, L. E. Suit, H. D. TI Radiation-Induced Sarcomas following Single-Dose Irradiation of C3Hf/Sed Mice with Dose-Response Relations SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Huang, P.; Kozin, S. V.; Gerweck, L. E.; Suit, H. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 632 EP 632 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000337 ER PT J AU Duran-Struuck, R AF Duran-Struuck, R. TI The MGH-MHC-Defined Miniature Pig as a Model for Graft versus Host Disease in Hematopoietic Cell Transplant Studies SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Duran-Struuck, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 633 EP 633 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000339 ER PT J AU Grant, RW Lutfey, KE Gerstenberger, E Link, CL Marceau, LD McKinlay, JB AF Grant, Richard W. Lutfey, Karen E. Gerstenberger, Eric Link, Carol L. Marceau, Lisa D. McKinlay, John B. TI The Decision to Intensify Therapy in Patients with Type 2 Diabetes: Results from an Experiment Using a Clinical Case Vignette SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article ID PRIMARY-CARE PHYSICIANS; INERTIA; MANAGEMENT; RISK; HYPERTENSION; SEX AB Purpose: Lack of medication intensification is a widely recognized but poorly understood barrier to effective diabetes care. We used a video case vignette to assess whether patient or physician demographic variables influence the decision to intensify therapy. Methods: One hundred ninety-two US primary care physicians each viewed one case vignette of an actor portraying a patient who had type 2 diabetes and borderline indications for medication intensification. Case vignettes were clinically identical and differed only by patient age (35 or 65 years old); sex; race/ethnicity (white, Hispanic, or black); and socioeconomic status (occupation of lawyer or janitor). After viewing the vignette and indicating their management plans, physicians were also asked to discuss the challenges related to managing such a patient. Results: Just over half (53%) of physicians indicated that they would recommend a medication prescription for the vignette patient. Demographic characteristics (of the patient, physician, or practice) did not significantly influence this decision (P > .1 for all comparisons). Compared with physicians who did not recommend a diabetic-related prescription, physicians recommending therapy more often identified patient medication costs (74% vs 43% of physicians who would not increase therapy); medication adherence (63% vs 49%); and subsequent complications (34% vs 22%) as important clinical issues in managing diabetes. Physicians not intensifying therapy more often indicated that they needed more clinical information (16% vs 9%). Conclusions: Using an experimental design we found that differences in the decision to intensify therapy were not significantly explained by patient, physician, or practice demographic variables. Physicians who intensified therapy were more likely to consider issues such as medication costs, patient adherence, and downstream complications. (J Am Board Fam Med 2009; 22: 513-520.) C1 [Grant, Richard W.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Grant, Richard W.] Harvard Univ, Sch Med, Boston, MA USA. [Lutfey, Karen E.; Gerstenberger, Eric; Link, Carol L.; Marceau, Lisa D.; McKinlay, John B.] New England Res Inst, Watertown, MA 02172 USA. RP Grant, RW (reprint author), 50-9 Staniford St, Boston, MA 02114 USA. EM Rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK Career Development Award [K23 DK067452]; National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases [DK66425] FX Funding: Dr. Grant was supported by NIDDK Career Development Award (K23 DK067452). This study was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, DK66425. NR 22 TC 11 Z9 11 U1 1 U2 4 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD SEP-OCT PY 2009 VL 22 IS 5 BP 513 EP 520 DI 10.3122/jabfm.2009.05.080232 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 491NU UT WOS:000269586600009 PM 19734397 ER PT J AU Curtis, JP Schreiner, G Wang, YF Chen, J Spertus, JA Rumsfeld, JS Brindis, RG Krumholz, HM AF Curtis, Jeptha P. Schreiner, Geoffrey Wang, Yongfei Chen, Jersey Spertus, John A. Rumsfeld, John S. Brindis, Ralph G. Krumholz, Harlan M. TI All-Cause Readmission and Repeat Revascularization After Percutaneous Coronary Intervention in a Cohort of Medicare Patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE angioplasty; quality of care; readmission ID ASSOCIATION; DISEASE; STENT AB Objectives The purpose of this study was to report on the all-cause readmission and repeat revascularization rates after percutaneous coronary intervention (PCI). Background Although PCIs are frequently performed, 30-day rates of readmission and repeat revascularization after PCI are not known. Methods Retrospective analysis of a cohort of Medicare fee-for-service admissions associated with a PCI in 2005. Primary outcomes were 30-day all-cause readmission rates and 30-day readmission rates associated with a revascularization procedure. Results A total of 315,241 PCI procedures performed at 1,108 hospitals were included in the analysis. The all-cause 30-day readmission rate was 14.6%, and the all-cause 30-day mortality rate was 1.0%. All-cause 30-day mortality among readmitted patients was higher than patients who were not readmitted (3.6% vs. 0.6%; p < 0.001). The 30-day readmission rate of acute myocardial infarction ( AMI) patients was significantly higher than that of non-AMI patients (AMI 17.5%, non-AMI 13.6%, p < 0.001). Among all patients readmitted within 30 days after the index PCI, 27.5% had an associated revascularization procedure (PCI 25.8%, coronary artery bypass grafting 1.7%). The median readmission rates varied across hospitals, from 8.9% in the lowest decile to 22.0% in the highest decile. Conclusions A substantial proportion of PCI patients are readmitted within 30 days of discharge, and readmission rates vary widely across hospitals. Readmissions within 30 days of an index PCI procedure were associated with a significantly higher 30-day mortality rate, and more than one-quarter of such readmissions resulted in a repeat revascularization procedure. These findings warrant further attention to determine whether these readmissions are preventable. (J Am Coll Cardiol 2009; 54:903-7) c 2009 by the American College of Cardiology Foundation C1 [Curtis, Jeptha P.; Wang, Yongfei; Chen, Jersey; Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Cardiovasc Med, Dept Internal Med, New Haven, CT 06520 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, Dept Internal Med, New Haven, CT 06520 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Hlth Policy & Adm, Sch Publ Hlth, New Haven, CT 06520 USA. [Curtis, Jeptha P.; Schreiner, Geoffrey; Wang, Yongfei; Chen, Jersey; Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Rumsfeld, John S.] Denver Vet Affairs Hosp, Denver, CO USA. [Brindis, Ralph G.] Oakland Kaiser Med Ctr, Oakland, CA USA. RP Curtis, JP (reprint author), Yale Univ, Sch Med, Sect Cardiovasc Dis, 333 Cedar St FMP 3, New Haven, CT 06520 USA. EM jeptha.curtis@yale.edu FU Centers for Medicare and Medicaid Services; U.S. Department of Health and Human Services; Johnson Johnson; [HHSM-500-2005-CO001] FX From the *Section of Cardiovascular Medicine, Department of Internal Medicine, dagger Robert Wood Johnson Clinical Scholars Program, Department of Internal Medicine, and the Section of Health Policy and Administration, School of Public Health, Yale University School of Medicine, New Haven, Connecticut; Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut; parallel to Mid-America Heart Institute, Kansas City, Missouri; Denver Veterans Affairs Hospital, Denver, Colorado; and the #Oakland Kaiser Medical Center, Oakland, California. The analyses on which this publication is based were performed under contract no. HHSM-500-2005-CO001, entitled "Utilization and Quality Control Quality Improvement Organization for the State (Commonwealth) of Colorado," funded by the Centers for Medicare and Medicaid Services, an agency of the U.S. Department of Health and Human Services. Dr. Spertus is on the Scientific Advisory Board for United Healthcare (modest), has received a research grant from Johnson & Johnson (significant), and serves an analytic center for the American College of Cardiology Foundation (significant). Dr. Krumholz is under contract with Centers for Medicare and Medicaid Services to develop measures. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. The authors assume full responsibility for the accuracy and completeness of the ideas presented. NR 9 TC 63 Z9 64 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 1 PY 2009 VL 54 IS 10 BP 903 EP 907 DI 10.1016/j.jacc.2009.04.076 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 487WY UT WOS:000269309900005 PM 19712799 ER PT J AU MacRae, CA McKenna, WJ AF MacRae, Calum A. McKenna, William J. TI Splicing and Dilated Cardiomyopathy One Gene to Rule Them All? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE dilated cardiomyopathy; genetics; linkage analysis; mutation; RBM20 ID HEART-FAILURE; FAMILY; MUSCLE; MOUSE C1 [McKenna, William J.] Heart Hosp, Ctr Cardiol Young, London W1G 8PH, England. [MacRae, Calum A.] Massachusetts Gen Hosp, Cardiol Div & Cardiovasc Res Ctr, Boston, MA 02114 USA. RP McKenna, WJ (reprint author), Heart Hosp, Ctr Cardiol Young, 16-18 Westmoreland St, London W1G 8PH, England. EM william.mckenna@uclh.org RI McKenna, William/C-3243-2008 OI McKenna, William/0000-0001-7994-2460 NR 17 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 1 PY 2009 VL 54 IS 10 BP 942 EP 943 DI 10.1016/j.jacc.2009.06.009 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 487WY UT WOS:000269309900011 PM 19712805 ER PT J AU Chen, K Malo, M Zeller, S Johnson, P Mostafa, G Alam, S Ramasamy, S Hohmann, E Hodin, RA AF Chen, Kathryn Malo, Madhu Zeller, Skye Johnson, Paul Mostafa, Golam Alam, Sayeda Ramasamy, Sundaram Hohmann, Elizabeth Hodin, Richard A. TI Intestinal alkaline phosphatase targeting of lipopolysaccharide SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 95th Annual Clinical Congress of the American-College-of-Surgeons/64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 11-15, 2009 CL Chicago, IL SP Amer Coll Surg C1 [Chen, Kathryn; Malo, Madhu; Zeller, Skye; Johnson, Paul; Mostafa, Golam; Alam, Sayeda; Ramasamy, Sundaram; Hohmann, Elizabeth; Hodin, Richard A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2009 VL 209 IS 3 SU S BP S12 EP S12 PG 1 WC Surgery SC Surgery GA 493RJ UT WOS:000269755300008 ER PT J AU Conrad, C Zhou, DW Park, JS Avruch, J Warshaw, A Bardeesy, N AF Conrad, Claudius Zhou, Dawang Park, Ji Sun Avruch, Joseph Warshaw, Andrew Bardeesy, Nabeel TI Mst1 and Mst2 control liver size and suppress the development of hepatocellular carcinoma SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 95th Annual Clinical Congress of the American-College-of-Surgeons/64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 11-15, 2009 CL Chicago, IL SP Amer Coll Surg C1 [Conrad, Claudius; Zhou, Dawang; Park, Ji Sun; Avruch, Joseph; Warshaw, Andrew; Bardeesy, Nabeel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2009 VL 209 IS 3 SU S BP S120 EP S120 PG 1 WC Surgery SC Surgery GA 493RJ UT WOS:000269755300268 ER PT J AU Conrad, C Husemann, Y Niess, H von Luttichau, I Huss, R Bauer, C Jauch, KW Klein, C Bruns, C Nelson, P AF Conrad, Claudius Huesemann, Yves Niess, Hanno von Luettichau, Irene Huss, Ralf Bauer, Christian Jauch, Karl-Walter Klein, Christoph Bruns, Christiane Nelson, Peter TI Targeting of tumor angiogenesis using engineered Trojan Horse mesenchymal stem cells SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 95th Annual Clinical Congress of the American-College-of-Surgeons/64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 11-15, 2009 CL Chicago, IL SP Amer Coll Surg C1 [Conrad, Claudius; Huesemann, Yves; Niess, Hanno; von Luettichau, Irene; Huss, Ralf; Bauer, Christian; Jauch, Karl-Walter; Klein, Christoph; Bruns, Christiane; Nelson, Peter] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2009 VL 209 IS 3 SU S BP S88 EP S89 PG 2 WC Surgery SC Surgery GA 493RJ UT WOS:000269755300196 ER PT J AU Conrad, C Niess, H Huss, R Huber, S von Lutichau, I Nelson, P Ott, H Jauch, KW Bruns, C AF Conrad, Claudius Niess, Hanno Huss, Ralf Huber, Stephan von Luetichau, Irene Nelson, Peter Ott, Harald Jauch, Karl-Walter Bruns, Christiane TI Multipotent mesenchymal stem cells acquire a lymphendothelial phenotype and enhance lymphatic regeneration in vivo SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 95th Annual Clinical Congress of the American-College-of-Surgeons/64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 11-15, 2009 CL Chicago, IL SP Amer Coll Surg C1 [Conrad, Claudius; Niess, Hanno; Huss, Ralf; Huber, Stephan; von Luetichau, Irene; Nelson, Peter; Ott, Harald; Jauch, Karl-Walter; Bruns, Christiane] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2009 VL 209 IS 3 SU S BP S86 EP S86 PG 1 WC Surgery SC Surgery GA 493RJ UT WOS:000269755300190 ER PT J AU Crawford, RS Albadawi, H Robaldo, A Peck, M Abularrage, C LaMuraglia, G Conrad, M Patel, V Watkins, M AF Crawford, Robert S. Albadawi, Hassan Robaldo, Alessandro Peck, Michael Abularrage, Christopher LaMuraglia, Glenn Conrad, Mark Patel, Virendra Watkins, Michael TI Exercise induces a systemic inflammatory response with and without chronic unilateral hind-limb ischemia SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 95th Annual Clinical Congress of the American-College-of-Surgeons/64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 11-15, 2009 CL Chicago, IL SP Amer Coll Surg C1 [Crawford, Robert S.; Albadawi, Hassan; Robaldo, Alessandro; Peck, Michael; Abularrage, Christopher; LaMuraglia, Glenn; Conrad, Mark; Patel, Virendra; Watkins, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2009 VL 209 IS 3 SU S BP S141 EP S142 PG 2 WC Surgery SC Surgery GA 493RJ UT WOS:000269755300322 ER PT J AU Kaafarani, HMA Rosen, AK Borzecki, AM Itani, KMF AF Kaafarani, Haytham M. A. Rosen, Amy K. Borzecki, Ann M. Itani, Kamal M. F. TI Validity of surgical quality indicators: Opportunities and concerns SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 95th Annual Clinical Congress of the American-College-of-Surgeons/64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 11-15, 2009 CL Chicago, IL SP Amer Coll Surg C1 [Kaafarani, Haytham M. A.; Rosen, Amy K.; Borzecki, Ann M.; Itani, Kamal M. F.] VA Boston Healthcare Syst, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2009 VL 209 IS 3 SU S BP S93 EP S93 PG 1 WC Surgery SC Surgery GA 493RJ UT WOS:000269755300207 ER PT J AU Kim, KM Veillette, GR Weiss, MJ Meltzer, AJ Cochrane, MC Sachs, DH Rosengard, BR Allan, JS Benichou, G Madsen, JC AF Kim, Karen M. Veillette, Gregory R. Weiss, Matthew J. Meltzer, Andrew J. Cochrane, Meghan C. Sachs, David H. Rosengard, Bruce R. Allan, James S. Benichou, Gilles Madsen, Joren C. TI Sensitization to cardiac myosin induces rejection of cardiac allografts in miniature swine SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 95th Annual Clinical Congress of the American-College-of-Surgeons/64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 11-15, 2009 CL Chicago, IL SP Amer Coll Surg C1 [Kim, Karen M.; Veillette, Gregory R.; Weiss, Matthew J.; Meltzer, Andrew J.; Cochrane, Meghan C.; Sachs, David H.; Rosengard, Bruce R.; Allan, James S.; Benichou, Gilles; Madsen, Joren C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2009 VL 209 IS 3 SU S BP S28 EP S28 PG 1 WC Surgery SC Surgery GA 493RJ UT WOS:000269755300048 ER PT J AU Millington, TM Tena, A Ng, C Kawai, T Allan, J Madsen, J Sachs, D Svjetlan, B Muniappan, A AF Millington, Timothy M. Tena, Aseda Ng, Choo Kawai, Tatsuo Allan, James Madsen, Joren Sachs, David Svjetlan, Boskovic Muniappan, Ashok TI Regeneration of naive T lymphocytes from heart-thymus grafts occurs at a low level and is associated with prolonged survival but not tolerance SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 95th Annual Clinical Congress of the American-College-of-Surgeons/64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 11-15, 2009 CL Chicago, IL SP Amer Coll Surg C1 [Millington, Timothy M.; Tena, Aseda; Ng, Choo; Kawai, Tatsuo; Allan, James; Madsen, Joren; Sachs, David; Svjetlan, Boskovic; Muniappan, Ashok] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2009 VL 209 IS 3 SU S BP S59 EP S59 PG 1 WC Surgery SC Surgery GA 493RJ UT WOS:000269755300124 ER PT J AU Gruenewald, TL Seeman, TE Karlamangla, AS Sarkisian, CA AF Gruenewald, Tara L. Seeman, Teresa E. Karlamangla, Arun S. Sarkisian, Catherine A. TI Allostatic Load and Frailty in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE frailty; allostatic load; physiological dysregulation; older adults ID CUMULATIVE BIOLOGICAL RISK; GROWTH-FACTOR-I; ELDERLY-PEOPLE; WOMENS HEALTH; UNITED-STATES; MACARTHUR; MORTALITY; AGE; INFLAMMATION; INTERLEUKIN-6 AB OBJECTIVES: To examine the association between allostatic load (AL), an index of multisystem physiological dysregulation, and frailty development over a 3-year follow-up in a sample of older adults. DESIGN: Longitudinal cohort study. SETTING: Community. PARTICIPANTS: High-functioning men and women aged 70 to 79 at study entry. MEASUREMENTS: Multisystem physiological dysregulation, or AL, was assessed according to 13 biomarkers of cardiovascular, endocrine, immune, and metabolic function. An AL score was computed as the total number of biomarkers for which participant values fell into high-risk biomarker quartiles. Frailty status (not frail, intermediate frail, frail) was determined according to the total number of five indicators of frailty: weight loss, exhaustion, weak grip, slow gait, and low physical activity. The association between level of AL at baseline and frailty status 3 years later was examined using ordinal logistic regression in 803 participants not frail at baseline. RESULTS: In a multivariable model adjusting for sociodemographic, health, and behavioral characteristics, each 1-unit increase in AL at baseline was associated with a 10% greater likelihood of frailty at the 3-year follow-up (cumulative adjusted odds ratio = 1.10, 95% confidence interval = 1.03-1.19). CONCLUSION: These findings support the hypothesis that dysregulation across multiple physiological systems is associated with greater risk of frailty. Greater levels of multisystem physiological dysregulation may serve as a warning sign of frailty development in later life. J Am Geriatr Soc 57:1525-1531, 2009. C1 [Gruenewald, Tara L.; Seeman, Teresa E.; Karlamangla, Arun S.; Sarkisian, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Dept Med, Los Angeles, CA 90095 USA. [Sarkisian, Catherine A.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, Los Angeles, CA USA. RP Gruenewald, TL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Geriatr Med, 1094S LeConte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM tgruenewald@mednet.ucla.edu FU National Institute on Aging [K01-AG028582, K23-AG024811, R21-AG025764]; University of Southern California/University of California at Los Angeles Center [P30-AG017265]; John D. and Catherine T. MacArthur Foundation FX This work Was Supported by National Institute on Aging Grants K01-AG028582 (PI: Gruenewald) and K23-AG024811 and R21-AG025764 (PI: Sarkisian), the University of Southern California/University of California at Los Angeles Center for the Study of Biodemography and Population Health (P30-AG017265), and the John D. and Catherine T. MacArthur Foundation, which funded the MSSA. NR 38 TC 62 Z9 63 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2009 VL 57 IS 9 BP 1525 EP 1531 DI 10.1111/j.1532-5415.2009.02389.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 492LQ UT WOS:000269659500001 PM 19682116 ER PT J AU Covinsky, KE Lindquist, K Dunlop, DD Yelin, E AF Covinsky, Kenneth E. Lindquist, Karla Dunlop, Dorothy D. Yelin, Edward TI Pain, Functional Limitations, and Aging SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pain; functional limitations; activities of daily living; quality of life; disability ID LIVING OLDER PERSONS; PHYSICAL FUNCTION; BACK-PAIN; DISABILITY; ADULTS; HEALTH; COMMUNITY; PREDICTORS; DEPENDENCE; MORBIDITY AB OBJECTIVES: To examine the relationship between functional limitations and pain across a spectrum of age, ranging from mid life to advanced old age. DESIGN: Cross-sectional study. SETTING: The 2004 Health and Retirement Study (HRS), a nationally representative study of community-living persons aged 50 and older. PARTICIPANTS: Eighteen thousand five hundred thirty-one participants in the 2004 HRS. MEASUREMENTS: Participants who reported that they were often troubled by pain that was moderate or severe most of the time were defined as having significant pain. For each of four functional domains, subjects were classified according to their degree of functional limitation: mobility (able to Jog 1 mile, able to walk several blocks, able to walk one block, unable to walk one block), stair climbing (able to climb several flights, able to climb one flight, not able to climb a flight), upper extremity tasks (able to do 3, 2, 1, or 0), and activity of daily living (ADL) function (able to do without difficulty, had difficulty but able to do without help, need help). RESULTS: Twenty-four percent of participants had significant pain. Across all four domains, participants with pain had much higher rates of functional limitations than subjects without pain. Participants with pain were similar in terms of their degree of functional limitation to participants 2 to 3 decades older. For example, for mobility, of subjects aged 50 to 59 without pain, 37% were able to jog 1 mile, 91% were able to walk several blocks, and 96% were able to walk one block without difficulty. In contrast, of subjects aged 50 to 59 with pain, 9% were able to jog 1 mile, 50% were able to walk several blocks, and 69% were able to walk one block without difficulty. Subjects aged 50 to 59 with pain were similar in terms of mobility limitations to subjects aged 80 to 89 without pain, of whom 4% were able to jog 1 mile, 55% were able to walk several blocks, and 72% were able to walk one block without difficulty. After adjustment for demographic characteristics, socioeconomic status, comorbid conditions, depression, obesity, and health habits, across all four measures, participants with significant pain were at much higher risk for having functional limitations (adjusted odds ratio (AOR) = 2.85, 95% confidence interval (CI) = 2.20-3.69, for mobility; AOR = 2.84, 95% CI = 2.48-3.26, for stair climbing; AOR = 3.96, 95% CI = 3.43-4.58, for upper extremity tasks; and AOR = 4.33; 95% CI = 3.71-5.06, for ADL function). CONCLUSION: Subjects with pain develop the functional limitations classically associated with aging at much earlier ages. J Am Geriatr Soc 57:1556-1561, 2009. C1 [Covinsky, Kenneth E.; Lindquist, Karla; Yelin, Edward] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Covinsky, Kenneth E.; Lindquist, Karla] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Covinsky, Kenneth E.; Lindquist, Karla] San Francisco VA Med Ctr, San Francisco, CA USA. [Dunlop, Dorothy D.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Dunlop, Dorothy D.] Northwestern Univ, Inst Healthcare Studies, Chicago, IL 60611 USA. RP Covinsky, KE (reprint author), Univ Calif San Francisco, Dept Med, 4150 Clement, San Francisco, CA 94121 USA. EM covinsky@medicine.ucsf.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [5P60AR053308-020]; National Institute on Aging [U01AG009740, 5K24AG029812-02] FX Supported by a Multidisciplinary Clinical Research Center Grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5P60AR053308-020). The Health and Retirement Study, the data source for this study, is funded by the National Institute on Aging (U01AG009740). Dr. Covinsky is supported in part by a midcareer investigator award from the National Institute on Aging (5K24AG029812-02). NR 27 TC 49 Z9 52 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2009 VL 57 IS 9 BP 1556 EP 1561 DI 10.1111/j.1532-5415.2009.02388.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 492LQ UT WOS:000269659500005 PM 19682122 ER PT J AU Ginde, AA Scragg, R Schwartz, RS Camargo, CA AF Ginde, Adit A. Scragg, Robert Schwartz, Robert S. Camargo, Carlos A., Jr. TI Prospective Study of Serum 25-Hydroxyvitamin D Level, Cardiovascular Disease Mortality, and All-Cause Mortality in Older US Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE vitamin D; mortality; cardiovascular disease; epidemiology; geriatrics ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; VITAMIN-D SUPPLEMENTATION; RESPIRATORY-TRACT INFECTION; CHRONIC KIDNEY-DISEASE; HEMODIALYSIS-PATIENTS; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; D DEFICIENCY; CANCER-RISK AB OBJECTIVES: To evaluate the association between serum 25-hydroxyvitamin D (25(OH)D) levels and mortality in a representative U.S. sample of older adults. DESIGN: Prospective cohort from the Third National Health and Nutrition Examination Survey (NHANES III) and linked mortality files. SETTING: Noninstitutionalized U.S. civilian population. PARTICIPANTS: Three thousand four hundred eight NHANES III participants aged 65 and older enrolled from 1988 to 1994 and followed for mortality through 2000. MEASUREMENTS: Primary exposure was serum 25(OH)D level at enrollment. Primary and secondary outcomes were all-cause and cardiovascular disease (CVD) mortality, respectively. RESULTS: During the median 7.3 years of follow-up, there were 1,493 (44%) deaths, including 767 CVD-related deaths. Median 25(OH)D level was 66 nmol/L. Adjusting for demographics, season, and cardiovascular risk factors, baseline 25(OH)D levels were inversely associated with all-cause mortality risk (adjusted hazard ratio (HR) = 0.95, 95% confidence interval (CI) = 0.92-0.98, per 10 nmol/L 25[OH]D). Compared with subjects with 25(OH)D levels of 100 nmol/L or higher, the adjusted HR for subjects with levels less than 25.0 nmol/L was 1.83 (95% CI = 1.14-2.94) and for levels of 25.0 to 49.9 nmol/L was 1.47 (95% CI = 1.09-1.97). The association appeared stronger for CVD mortality (adjusted HR = 2.36, 95% CI = 1.17-4.75, for subjects with 25[OH]D levels < 25.0 nmol/L vs those >= 100.0 nmol/L) than for non-CVD mortality (adjusted HR = 1.42, 95% CI = 0.73-2.79, for subjects with 25[OH]D levels < 25.0 nmol/L vs those >= 100.0 nmol/L). CONCLUSION: In noninstitutionalized older adults, a group at high risk for all-cause mortality, serum 25(OH)D levels had an independent, inverse association with CVD and all-cause mortality. Randomized controlled trials of vitamin D supplementation in older adults are warranted to determine whether this association is causal and reversible. J Am Geriatr Soc 57:1595-1603, 2009. C1 [Ginde, Adit A.] Univ Colorado Denver, Sch Med, Dept Emergency Med, Aurora, CO 80045 USA. [Scragg, Robert] Univ Colorado Denver, Sch Med, Div Geriatr Med, Aurora, CO 80045 USA. [Schwartz, Robert S.] Univ Auckland, Sch Populat Hlth, Auckland 1, New Zealand. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Ginde, AA (reprint author), Univ Colorado Denver, Sch Med, Dept Emergency Med, 12401 E 17th Ave,B-215, Aurora, CO 80045 USA. EM adit.ginde@ucdenver.edu RI Siry, Bonnie/D-7189-2017; OI Scragg, Robert/0000-0003-0013-2620 FU University of Colorado Denver Hartford/Jahnigen Center of Excellence in Geriatrics; National Institutes of Health (NIH) [KL2 RR025779, R01 AG019339, R01 AG028746, R01 HL84401]; Health Research Council of New Zealand; Massachusetts General Hospital Center FX Dr. Ginde was supported by the University of Colorado Denver Hartford/Jahnigen Center of Excellence in Geriatrics and National Institutes of Health (NIH) Grant KL2 RR025779. Dr. Scragg was supported by the Health Research Council of New Zealand. Dr. Schwartz was supported by NIH Grants R01 AG019339 and R01 AG028746. Dr. Camargo was supported by the Massachusetts General Hospital Center for D-receptor Activation Research and NIH Grant R01 HL84401. NR 50 TC 195 Z9 201 U1 1 U2 13 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2009 VL 57 IS 9 BP 1595 EP 1603 DI 10.1111/j.1532-5415.2009.02359.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 492LQ UT WOS:000269659500010 PM 19549021 ER PT J AU Zoghbi, WA Chambers, JB Dumesnil, JG Foster, E Gottdiener, JS Grayburn, PA Khandheria, BK Levine, RA Marx, GR Miller, FA Nakatani, S Quinones, MA Rakowski, H Rodriguez, LL Swaminathan, M Waggoner, AD Weissman, NJ Zabalgoitia, M AF Zoghbi, William A. Chambers, John B. Dumesnil, Jean G. Foster, Elyse Gottdiener, John S. Grayburn, Paul A. Khandheria, Bijoy K. Levine, Robert A. Marx, Gerald Ross Miller, Fletcher A., Jr. Nakatani, Satoshi Quinones, Miguel A. Rakowski, Harry Rodriguez, L. Leonardo Swaminathan, Madhav Waggoner, Alan D. Weissman, Neil J. Zabalgoitia, Miguel TI Recommendations for Evaluation of Prosthetic Valves With Echocardiography and Doppler Ultrasound A Report From the American Society of Echocardiography's Guidelines and Standards Committee and the Task Force on Prosthetic Valves, Developed in Conjunction With the American College of Cardiology Cardiovascular Imaging Committee, Cardiac Imaging Committee of the American Heart Association, the European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography and the Canadian Society of Echocardiography, Endorsed by the American College of Cardiology Foundation, American Heart Association, European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography, and Canadian Society of Echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Review ID VENTRICULAR OUTFLOW TRACT; VELOCITY INTEGRAL RATIO; LONG-TERM SURVIVAL; MULTIDETECTOR COMPUTED-TOMOGRAPHY; MEDICAL MECHANICAL PROSTHESES; TRANS-SEPTAL CATHETERIZATION; PRESSURE RECOVERY DISTAL; BJORK-SHILEY PROSTHESIS; OUTLET STRUT FRACTURE; AORTIC-VALVE C1 [Zoghbi, William A.; Quinones, Miguel A.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [Chambers, John B.] St Thomas Hosp, London, England. [Dumesnil, Jean G.] Hosp Laval, Quebec City, PQ, Canada. [Foster, Elyse] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gottdiener, John S.] Univ Maryland Hosp, Baltimore, MD 21201 USA. [Grayburn, Paul A.] Baylor Univ, Med Ctr, Dallas, TX USA. [Khandheria, Bijoy K.] Mayo Clin, Scottsdale, AZ USA. [Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marx, Gerald Ross] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Miller, Fletcher A., Jr.] Mayo Clin, Rochester, MN USA. [Nakatani, Satoshi] Osaka Univ, Grad Sch Med, Suita, Osaka, Japan. [Rakowski, Harry] Toronto Gen Hosp, Toronto, ON, Canada. [Rodriguez, L. Leonardo] Cleveland Clin, Cleveland, OH 44106 USA. [Swaminathan, Madhav] Duke Univ, Med Ctr, Durham, NC USA. [Waggoner, Alan D.] Washington Univ, Sch Med, St Louis, MO USA. [Weissman, Neil J.] Washington Hosp Ctr, Washington, DC 20010 USA. [Zabalgoitia, Miguel] Prairie Cardiovasc Consultants, Springfield, IL USA. RP Zoghbi, WA (reprint author), 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. NR 185 TC 400 Z9 409 U1 1 U2 15 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 SEP PY 2009 VL 22 IS 9 BP 975 EP 1014 DI 10.1016/j.echo.2009.07.013 PG 40 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 491GS UT WOS:000269567200001 PM 19733789 ER PT J AU Lam, KMT Ennis, S O'Driscoll, G Solis, JM MacGillivray, T Picard, MH AF Lam, Kaitlyn My-Tu Ennis, Stephanie O'Driscoll, Gerry Solis, Jorge M. MacGillivray, Thomas Picard, Michael H. TI Observations From Non-Invasive Measures of Right Heart Hemodynamics in Left Ventricular Assist Device Patients SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Ventricular assist device; Right-heart hemodynamics; Right ventricular function; HeartMate II ID PULMONARY-HYPERTENSION; TRANSPLANT CANDIDATES; FAILURE; SUPPORT; ECHOCARDIOGRAPHY; RECOMMENDATIONS; DYSFUNCTION; MANAGEMENT; PRESSURE; RISK AB Background: Left ventricular assist devices (LVADs) reduce pulmonary vascular resistance (PVR) in patients with severe heart failure. The aim of this study was to noninvasively assess the effect of LVAD implantation on PVR and right-heart function. Methods: In 21 patients with HeartMate II LVADs, serial echocardiograms were reviewed prior to implantation and 1 and 6 months after implantation. Echocardiographic and Doppler indices of right-heart structure and function were measured along with LVAD settings, hemodynamics, and biochemistry, and the Minnesota Living With Heart Failure Questionnaire (MLHFQ) and 6-minute walk test were administered. Results: Comparing values before and 1 month after implantation, there were reductions in PVR (3.51 +/- 0.9 vs 2.0 +/- 0.5 Wood units, P < .0001), right ventricular (RV) systolic pressure (49 +/- 11 vs 34 +/- 7 mm Hg, P < .0001), and tricuspid regurgitation severity, with no change in RV size, RV fractional area change, or tricuspid annular plane systolic excursion. Patients with larger PVR reductions had better clinical status (MLHFQ score, 28 +/- 12 vs 60 +/- 29, P = .04; 6-minute walking distance, 1706 +/- 71 vs 1141 +/- 387 ft, P = .04). Patients with significant deteriorations in RV function had poorer clinical status (MLHFQ score, 79 +/- 13 vs 51 +/- 27, P = .04; 6-minute walking distance, 480 +/- 275 vs 1030 +/- 437 ft, P = .04). Conclusions: Echocardiographically detected changes in right-heart hemodynamics were associated with symptomatic status after LVAD implantation. (J Am Soc Echocardiogr 2009; 22: 1055-62.) C1 [Lam, Kaitlyn My-Tu; Solis, Jorge M.; Picard, Michael H.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Ennis, Stephanie; MacGillivray, Thomas] Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. [O'Driscoll, Gerry] Royal Perth Hosp, Adv Heart Failure & Cardiac Transplant Unit, Perth, WA, Australia. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Yawkey 5E,55 Fruit St, Boston, MA 02114 USA. EM mhpicard@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 23 TC 28 Z9 28 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD SEP PY 2009 VL 22 IS 9 BP 1055 EP 1062 DI 10.1016/j.echo.2009.06.006 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 491GS UT WOS:000269567200008 PM 19647406 ER PT J AU Upadhyay, A Hwang, SJ Mitchell, GF Vasan, RS Vita, JA Stantchev, PI Meigs, JB Larson, MG Levy, D Benjamin, EJ Fox, CS AF Upadhyay, Ashish Hwang, Shih-Jen Mitchell, Gary F. Vasan, Ramachandran S. Vita, Joseph A. Stantchev, Plamen I. Meigs, James B. Larson, Martin G. Levy, Daniel Benjamin, Emelia J. Fox, Caroline S. TI Arterial Stiffness in Mild-to-Moderate CKD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; PULSE-WAVE VELOCITY; URINARY ALBUMIN EXCRETION; INCREASED AORTIC STIFFNESS; INTIMA-MEDIA THICKNESS; STAGE RENAL-DISEASE; SERUM CYSTATIN-C; ESSENTIAL-HYPERTENSION; SYSTOLIC HYPERTENSION AB Whether arterial stiffness correlates with mild-to-moderate CKD and albuminuria in the community is unclear. We studied the association between arterial stiffness and mild-to-moderate CKD and albuminuria in the Framingham Heart Study. CKD was present in 6.7% (181 of 2682) of participants and microalbuminuria was present in 8.2% (479 of 5818). The measures of arterial stiffness were the carotid femoral pulse wave velocity, forward pressure wave amplitude, central pulse pressure, augmentation pressure, augmentation index, and mean arterial pressure. In cross-sectional analyses, arterial stiffness did not associate with CKD (defined by estimated GFR <60 ml/min/1.73 m(2)) in either age- and gender-adjusted or multivariable-adjusted linear regression models. Carotid femoral pulse wave velocity associated with both urinary albumin-to-creatinine ratio and microalbuminuria (P < 0.0001 after multivariable adjustment). In longitudinal analyses, we used logistic regression models to examine the associations between baseline arterial stiffness measures (exposure variables) and incident CKD or microalbuminuria (n = 1675 for CKD analyses and n = 1252 for microalbuminuria analyses). Baseline arterial measures did not associate with incident CKD or incident microalbuminuria. In summary, arterial stiffness correlates with albuminuria but not with mild-to-moderate CKD. C1 [Hwang, Shih-Jen; Vasan, Ramachandran S.; Stantchev, Plamen I.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA 01702 USA. [Upadhyay, Ashish] Boston Med Ctr, Renal Sect, Boston, MA USA. [Vasan, Ramachandran S.; Vita, Joseph A.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Hwang, Shih-Jen; Vasan, Ramachandran S.; Stantchev, Plamen I.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA. [Vasan, Ramachandran S.; Vita, Joseph A.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Meigs, James B.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Fox, CS (reprint author), Natl Heart Lung & Blood Inst Framingham Heart Stu, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Upadhyay, Ashish/0000-0002-0536-5776; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [N01-HC-25195, 2-K24HL04334]; National Institute of Health [R01-HL-077477, RO1-HL076784, RO1-AG028321, R01-HL70100, RO1-HL60040, RO1-HL080124]; American Diabetes Association research grant; National Institute of Diabetes and Digestive and Kidney Diseases [K24-DK080140] FX The Framingham Heart Study is supported by National Heart, Lung, and Blood Institute Grant N01-HC-25195. Additional funding provided by National Heart, Lung, and Blood Institute Grant 2-K24HL04334 and National Institute of Health Grant R01-HL-077477 to R.S.V., an American Diabetes Association research grant and National Institute of Diabetes and Digestive and Kidney Diseases Grant K24-DK080140 to J.B.M., and National Institute of Health Grants RO1-HL076784, RO1-AG028321, R01-HL70100, RO1-HL60040, and RO1-HL080124 to E.J.B. NR 53 TC 58 Z9 63 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2009 VL 20 IS 9 BP 2044 EP 2053 DI 10.1681/ASN.2009010074 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 499TL UT WOS:000270248700027 PM 19608701 ER PT J AU Merchant, ML Perkins, BA Boratyn, GM Ficociello, LH Wilkey, DW Barati, MT Bertram, CC Page, GP Rovin, BH Warram, JH Krolewski, AS Klein, JB AF Merchant, Michael L. Perkins, Bruce A. Boratyn, Grzegorz M. Ficociello, Linda H. Wilkey, Daniel W. Barati, Michelle T. Bertram, Clinton C. Page, Grier P. Rovin, Brad H. Warram, James H. Krolewski, Andrzej S. Klein, Jon B. TI Urinary Peptidome May Predict Renal Function Decline in Type 1 Diabetes and Microalbuminuria SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PROTEOMIC ANALYSIS; NEPHROPATHY; COLLAGEN; RISK; HYPERGLYCEMIA; GLOMERULI; GRANULES; MELLITUS; STRESS; MICE AB One third of patients with type 1 diabetes and microalbuminuria experience an early, progressive decline in renal function that leads to advanced stages of chronic kidney disease and ESRD. We hypothesized that the urinary proteome may distinguish between stable renal function and early renal function decline among patients with type 1 diabetes and microalbuminuria. We followed patients with normal renal function and microalbuminuria for 10 to 12 yr and classified them into case patients (n = 21) with progressive early renal function decline and control subjects (n = 40) with stable renal function. Using liquid chromatography matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we identified three peptides that decreased in the urine of patients with early renal function decline [fragments of alpha 1(IV) and alpha 1(V) collagens and tenascin-X] and three peptides that increased (fragments of inositol pentakisphosphate 2-kinase, zona occludens 3, and FAT tumor suppressor 2). In renal biopsies from patients with early nephropathy from type 1 diabetes, we observed increased expression of inositol pentakisphosphate 2-kinase, which was present in granule-like cytoplasmic structures, and zona occludens 3. These results indicate that urinary peptide fragments reflect changes in expression of intact protein in the kidney, suggesting new potential mediators of diabetic nephropathy and candidate biomarkers for progressive renal function decline. C1 [Merchant, Michael L.; Boratyn, Grzegorz M.; Wilkey, Daniel W.; Barati, Michelle T.; Bertram, Clinton C.; Klein, Jon B.] Univ Louisville, Kidney Dis Program, Louisville, KY 40292 USA. [Merchant, Michael L.; Boratyn, Grzegorz M.; Wilkey, Daniel W.; Barati, Michelle T.; Bertram, Clinton C.; Klein, Jon B.] Univ Louisville, Clin Prote Ctr, Louisville, KY 40292 USA. [Klein, Jon B.] Vet Adm Med Ctr, Louisville, KY 40202 USA. [Perkins, Bruce A.; Ficociello, Linda H.; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Krolewski, Andrzej S.] Harvard Univ, Sch Med, Brigham & Women Hosp, Dept Med, Boston, MA 02215 USA. [Perkins, Bruce A.] Univ Toronto, Div Endocrinol, Toronto, ON, Canada. [Page, Grier P.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Rovin, Brad H.] Ohio State Univ, Sch Med, Dept Med, Columbus, OH 43210 USA. RP Krolewski, AS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Room 368,1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu; jon.klein@louisville.edu RI Klein, Jon/B-9833-2013; Merchant, Michael/F-7109-2013 FU National Institutes of Health [RO1 DK067638, ROI DK041526]; DOE [DE-FG02-05ER6406]; Department of Veterans Affairs FX This work was supported by National Institutes of Health grants RO1 DK067638 (A.S.K. and J.B.K.), ROI DK041526 (A.S.K.), and DOE DE-FG02-05ER6406 (J.B.K. and M.L.M.) and the Department of Veterans Affairs (J.B.K.). NR 28 TC 81 Z9 87 U1 2 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2009 VL 20 IS 9 BP 2065 EP 2074 DI 10.1681/ASN.2008121233 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 499TL UT WOS:000270248700029 PM 19643930 ER PT J AU Othus, M Li, Y Tiwari, RC AF Othus, Megan Li, Yi Tiwari, Ram C. TI A Class of Semiparametric Mixture Cure Survival Models With Dependent Censoring SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Estimating equation; Proportional hazards model; Proportional odds model; Right censoring; Transformation model ID COMPETING RISKS MODEL; PROSTATE-CANCER CELLS; SUFFICIENT FOLLOW-UP; TRANSFORMATION MODELS; REGRESSION-MODELS; FAILURE TIMES; IDENTIFIABILITY; PROBABILITY; CHOLESTEROL; DISEASE AB Modern cancer treatments have substantially improved cure rates and have generated a great interest in and need for proper statistical tools to analyze survival data with nonnegligible cure fractions. Data with Cure fractions often ire complicated by dependent censoring, and the analysis of this type of data typically involves untestable parametric assumptions on the dependence of the censoring mechanism and the true survival times. Motivated by the analysis of prostate cancer survival trends, we propose a class of semiparametric transformation cure models that allows for dependent censoring without making parametric assumptions on the dependence relationship. The proposed class of models encompasses a number of common models for the latency survival function, including the proportional hazards model and the proportional odds model, and also allows for time-dependent covariates. An inverse censoring probability reweighting scheme is used to derive unbiased estimating equations. Small-sample properties with simulations are derived, and the method is demonstrated with a data application. C1 [Othus, Megan; Li, Yi] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Othus, Megan; Li, Yi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Tiwari, Ram C.] NCI, Bethesda, MD 20892 USA. RP Othus, M (reprint author), Harvard Univ, Dept Biostat, Boston, MA 02115 USA. EM mothus@fas.harvard.edu; yili@jimmy.harvard.edu; ram.tiwari@fda.hhs.gov FU National Institutes of Health [CA09337-25, ES07142-24] FX Megan Othus is Graduate Student, Department of Biostatistics, Harvard University and Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115 (E-mail: mothus@fas.harvard.edu). Yi Li is Associate Professor, Department of Biostatistics, Harvard University, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115 (E-mail: yili@jimmy.harvard.edu). Ram Tiwari is Associate Director for Statistical Science and Policy, Office of Biostatistics, Center for Drug Evaluation & Research, Food and Drug Administration, Silver Springs, MD 20993 (E-mail: ram.tiwari@fda.hhs.gov). The work of Tiwari was conducted while he was at the National Cancer Institute. The views expressed in this article are his own and do not necessarily represent those of the National Cancer Institue or the Food and Drug Administration. This work was supported in part by National Institutes of Health grants CA09337-25 and ES07142-24. The authors thank Eric (Rocky) Feuer and Angela Mariotto for their extensive and insightful comments on the manuscript. NR 61 TC 6 Z9 6 U1 0 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2009 VL 104 IS 487 BP 1241 EP 1250 DI 10.1198/jasa.2009.tm08033 PG 10 WC Statistics & Probability SC Mathematics GA 508FX UT WOS:000270916100036 PM 20706564 ER PT J AU Goldstein, G Panchalingam, K McClure, RJ Stanley, JA Calhoun, VD Pearlson, GD Pettegrew, JW AF Goldstein, Gerald Panchalingam, Kanagasabai McClure, Richard J. Stanley, Jeffrey A. Calhoun, Vince D. Pearlson, Godfrey D. Pettegrew, Jay W. TI Molecular neurodevelopment: An in vivo (31)P-(1)H MRSI study SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Magnetic resonance spectroscopy; Phospholipid metabolism; Cognition; Phosphocreatine; Synapses; Brain; Child development; Adolescent development ID L-ASPARTIC ACID; MAGNETIC-RESONANCE SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; HUMAN CEREBRAL-CORTEX; HUMAN BRAIN; RAT-BRAIN; METABOLITE CONCENTRATIONS; DIFFERENTIAL DISTRIBUTION; DEVELOPMENTAL-CHANGES; ENZYMATIC SYNTHESIS AB Synaptic development and elimination are normal neurodevelopmental processes, which if altered Could contribute to various neuropsychiatric disorders. (31)P-(1)H magnetic resonance spectroscopic imaging (MRSI) and structural magnetic resonance imaging (MRI) exams were conducted on 105 healthy children ages 6-18 years old to identify neuromolecular indices of synaptic development and elimination. Over the age range Studied, age-related changes in high-energy phosphate (phosphocreatine), membrane phospholipid metabolism (precursors and breakdown products), and percent gray matter volume were found. These neuromolecular and structural indices of synaptic development and elimination are associated with development of several cognitive domains. Monitoring of these molecular markers is essential for devising treatment strategies for neurodevelopmental disorders. (JINS, 2009, 15, 671-683.) C1 [Panchalingam, Kanagasabai; McClure, Richard J.; Pettegrew, Jay W.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Pettegrew, Jay W.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Pettegrew, Jay W.] Univ Pittsburgh, Sch Med, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15261 USA. [Pettegrew, Jay W.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA. [Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Stanley, Jeffrey A.] Wayne State Univ, Sch Med, Dept Psychiat, Detroit, MI USA. [Stanley, Jeffrey A.] Wayne State Univ, Sch Med, Dept Behav Neurosci, Detroit, MI USA. [Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Calhoun, Vince D.; Pearlson, Godfrey D.] Yale Univ, Dept Psychiat, Hartford, CT USA. RP Pettegrew, JW (reprint author), Neurophys Lab, RIDC Pk,260 Kappa Dr, Pittsburgh, PA 15238 USA. EM pettegre+@pitt.edu RI Calhoun, Vince/H-7146-2013 OI Calhoun, Vince/0000-0001-9058-0747 FU NIHCD/NIH [HD-39799]; Medical Research Service; VISN-IV Mental Illness, Research, Education, and Clinical Center (MIRECC), Department of Veterans Affairs FX This work was supported in part by an NIHCD/NIH HD-39799 grant (JWP). We thank Terry Bradbury for conducting neuropsychological testing. Indebtedness is also expressed to the Medical Research Service and the VISN-IV Mental Illness, Research, Education, and Clinical Center (MIRECC), Department of Veterans Affairs, for Support of this work. We thank Harriet Marshman, Deborah Wetzler, and Dennis McKeag for help in conducting the study. There is no conflict of interest on the part of any of the authors. NR 71 TC 13 Z9 13 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD SEP PY 2009 VL 15 IS 5 BP 671 EP 683 DI 10.1017/S1355617709990233 PG 13 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 489IZ UT WOS:000269415100004 PM 19674503 ER PT J AU Toomey, R Alpern, R Vasterling, JJ Baker, DG Reda, DJ Lyons, MJ Henderson, WG Kang, HK Eisen, SA Murphy, FM AF Toomey, Rosemary Alpern, Renee Vasterling, Jennifer J. Baker, Dewleen G. Reda, Domenic J. Lyons, Michael J. Henderson, William G. Kang, Han K. Eisen, Seth A. Murphy, Frances M. TI Neuropsychological functioning of US Gulf War veterans 10 years after the war SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Cognition; Psychological tests; Neurotoxicity syndromes; Environmental medicine; Mental disorders; Psychological stress ID POSTTRAUMATIC-STRESS-DISORDER; PERSIAN-GULF; PREMORBID INTELLIGENCE; ARMY VETERANS; ERA VETERANS; HEALTH; ILLNESS; ATTENTION; PERFORMANCE; DYSFUNCTION AB Many U.S. Gulf War-era veterans complained of poor cognition following the war. This study assessed neuropsychological functioning in veterans 10 years after the war through objective tests. 2189 Gulf War-era veterans (1061 deployed, 1128 non-deployed) were examined at I of 16 U.S. Veterans Affairs medical centers. Outcomes included neuropsychological domains derived from factor analysis and individual test scores. Deployed veterans performed significantly worse than non-deployed veterans oil 2 of 8 factors (motor speed & sustained attention, analysis not corrected for multiple comparisons) and oil 4 of 27 individual test variables (Trails A & B, California Verbal Learning Test - List B, and Continuous Performance Test sensitivity, with only Traits B surviving Bonferroni correction). Within deployed veterans, Khamisiyah exposure was negatively correlated with motor speed after controlling for emotional distress. Depressive symptoms and self-reported exposure to toxicants were independently and significantly associated with worse sustained attention. Other factors were also associated with self-reported exposures. The findings were not a result of differential effort across groups. Gulf War deployment is associated with subtle declines of motor speed and sustained attention, despite overall intact neuropsychological functioning. Evidence suggests that toxicant exposures influence both these functions, and depressive symptoms also influence attention. (JINS, 2009, 15, 717-729.) C1 [Toomey, Rosemary; Lyons, Michael J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Toomey, Rosemary; Lyons, Michael J.] Boston VA Healthcare Syst, Res Serv, Boston, MA USA. [Toomey, Rosemary; Lyons, Michael J.] Harvard Univ, Sch Med, Dept Psychiat,Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Publ Acad Psychiat, Boston, MA 02115 USA. [Toomey, Rosemary; Lyons, Michael J.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Alpern, Renee; Reda, Domenic J.; Henderson, William G.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program, Coordinating Ctr, Hines, IL 60141 USA. [Vasterling, Jennifer J.] New Orleans Vet Affairs Med Ctr, VA S Cent Mental Illness Res Educ & Clin Ctr VISN, New Orleans, LA USA. [Vasterling, Jennifer J.] Tulane Univ, Sch Med, Dept Psychiat & Neurol, New Orleans, LA 70112 USA. [Baker, Dewleen G.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA. [Baker, Dewleen G.] Cincinnati VA Med Ctr, Psychiat Serv, Cincinnati, OH USA. [Kang, Han K.] Environm Epidemiol Serv, Dept Vet Affairs, Washington, DC USA. [Eisen, Seth A.] St Louis Dept Vet Affairs Med Ctr, Med Serv, St Louis, MO USA. [Eisen, Seth A.] Washington Univ, Sch Med, Dept Internal Med, Div Gen Med Sci, St Louis, MO 63110 USA. [Eisen, Seth A.] Vet Adm, Hlth Serv Res, Washington, DC USA. [Murphy, Frances M.] US Dept Vet Affairs, Vet Hlth Adm, Washington, DC USA. [Murphy, Frances M.] Uniformed Serv Univ Hlth Sci, Washington, DC USA. [Eisen, Seth A.] St Louis Dept Vet Affairs Med Ctr, Res Serv, St Louis, MO USA. [Eisen, Seth A.] Vet Adm, Hlth Serv Dev, Washington, DC USA. RP Toomey, R (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM rosemary_toomey@hms.harvard.edu RI Lyons, Michael/B-6119-2011; OI Lyons, Michael/0000-0001-6516-9219 FU Cooperative Studies Program of the Department of Veterans Affairs, Office of Research and Development FX This study was supported by the Cooperative Studies Program of the Department of Veterans Affairs, Office of Research and Development. Nine authors of the study were employed by the VA at the time of the study, while one author (MJL) was a paid consultant for the Study. The information in this manuscript and the manuscript itself has never been published either electronically or in print. NR 66 TC 19 Z9 19 U1 2 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD SEP PY 2009 VL 15 IS 5 BP 717 EP 729 DI 10.1017/S1355617709990294 PG 13 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 489IZ UT WOS:000269415100008 PM 19640317 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Colon Cancer: The New Breast Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2009 VL 7 IS 8 BP 773 EP 773 PG 1 WC Oncology SC Oncology GA 501YR UT WOS:000270421100001 PM 19755044 ER PT J AU Engstrom, PF Arnoletti, JP Benson, AB Chen, YJ Choti, MA Cooper, HS Covey, A Dilawari, RA Early, DS Enzinger, PC Fakih, MG Fleshman, J Fuchs, C Grem, JL Kiel, K Knol, JA Leong, LA Lin, E Mulcahy, MF Rao, S Ryan, DP Saltz, L Shibata, D Skibber, JM Sofocleous, C Thomas, J Venook, AP Willett, C AF Engstrom, Paul F. Arnoletti, Juan Pablo Benson, Al B., III Chen, Yi-Jen Choti, Michael A. Cooper, Harry S. Covey, Anne Dilawari, Raza A. Early, Dayna S. Enzinger, Peter C. Fakih, Marwan G. Fleshman, James, Jr. Fuchs, Charles Grem, Jean L. Kiel, Krystyna Knol, James A. Leong, Lucille A. Lin, Edward Mulcahy, Mary F. Rao, Sujata Ryan, David P. Saltz, Leonard Shibata, David Skibber, John M. Sofocleous, Constantinos Thomas, James Venook, Alan P. Willett, Christopher TI Colon Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; colonic neoplasms; colorectal surgery; adjuvant chemotherapy; 5-fluorouracil; adenocarcinoma; neoplasm staging; neoplasm recurrence; irinotecan; oxaliplatin ID METASTATIC COLORECTAL-CANCER; FLUOROURACIL PLUS LEUCOVORIN; HIGH-DOSE LEUCOVORIN; LONG-TERM SURVIVAL; PHASE-III TRIAL; RANDOMIZED CONTROLLED-TRIAL; GROWTH-FACTOR RECEPTOR; OXALIPLATIN-BASED CHEMOTHERAPY; UNRESECTABLE LIVER METASTASES; LYMPH-NODE MICROMETASTASES C1 [Engstrom, Paul F.; Cooper, Harry S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Arnoletti, Juan Pablo] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Benson, Al B., III; Kiel, Krystyna; Mulcahy, Mary F.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Choti, Michael A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Covey, Anne; Saltz, Leonard; Sofocleous, Constantinos] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Dilawari, Raza A.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Early, Dayna S.; Fleshman, James, Jr.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Early, Dayna S.; Fleshman, James, Jr.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Enzinger, Peter C.; Fuchs, Charles] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Fakih, Marwan G.] Roswell Pk Canc Inst, Buffalo, NY USA. [Grem, Jean L.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Knol, James A.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Lin, Edward; Rao, Sujata] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Skibber, John M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Thomas, James] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Venook, Alan P.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Willett, Christopher] Duke Comprehens Canc Ctr, Durham, NC USA. RP Engstrom, PF (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. OI Saltz, Leonard/0000-0001-8353-4670 NR 304 TC 182 Z9 198 U1 1 U2 18 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2009 VL 7 IS 8 BP 778 EP 831 PG 54 WC Oncology SC Oncology GA 501YR UT WOS:000270421100003 PM 19755046 ER PT J AU Engstrom, PF Arnoletti, JP Benson, AB Chen, YJ Choti, MA Cooper, HS Covey, A Dilawari, RA Early, DS Enzinger, PC Fakih, MG Fleshman, J Fuchs, C Grem, JL Kiel, K Knol, JA Leong, LA Lin, E Mulcahy, MF Rao, S Ryan, DP Saltz, L Shibata, D Skibber, JM Sofocleous, C Thomas, J Venook, AP Willett, C AF Engstrom, Paul F. Arnoletti, Juan Pablo Benson, Al B., III Chen, Yi-Jen Choti, Michael A. Cooper, Harry S. Covey, Anne Dilawari, Raza A. Early, Dayna S. Enzinger, Peter C. Fakih, Marwan G. Fleshman, James, Jr. Fuchs, Charles Grem, Jean L. Kiel, Krystyna Knol, James A. Leong, Lucille A. Lin, Edward Mulcahy, Mary F. Rao, Sujata Ryan, David P. Saltz, Leonard Shibata, David Skibber, John M. Sofocleous, Constantinos Thomas, James Venook, Alan P. Willett, Christopher TI Rectal Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; rectal neoplasms; colorectal surgery; adjuvant chemotherapy; adjuvant radiotherapy; fluorouracil; neoplasm staging; neoplasm recurrence; irinotecan; oxaliplatin ID COLORECTAL LIVER METASTASES; TOTAL MESORECTAL EXCISION; III COLON-CANCER; LONG-TERM SURVIVAL; CIRCUMFERENTIAL RESECTION MARGIN; LYMPH-NODE METASTASES; PREOPERATIVE PELVIC CHEMORADIOTHERAPY; FLUOROURACIL-BASED CHEMOTHERAPY; PATHOLOGICAL COMPLETE RESPONSE; PROSPECTIVE RANDOMIZED-TRIAL C1 [Engstrom, Paul F.; Cooper, Harry S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Arnoletti, Juan Pablo] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Benson, Al B., III; Kiel, Krystyna; Mulcahy, Mary F.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Choti, Michael A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Covey, Anne; Saltz, Leonard; Sofocleous, Constantinos] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Dilawari, Raza A.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Early, Dayna S.; Fleshman, James, Jr.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Early, Dayna S.; Fleshman, James, Jr.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Enzinger, Peter C.; Fuchs, Charles] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Fakih, Marwan G.] Roswell Pk Canc Inst, Buffalo, NY USA. [Grem, Jean L.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Knol, James A.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Lin, Edward; Rao, Sujata] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Skibber, John M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Thomas, James] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Venook, Alan P.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Willett, Christopher] Duke Comprehens Canc Ctr, Durham, NC USA. RP Engstrom, PF (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. OI Saltz, Leonard/0000-0001-8353-4670 NR 242 TC 125 Z9 145 U1 0 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2009 VL 7 IS 8 BP 838 EP 881 PG 44 WC Oncology SC Oncology GA 501YR UT WOS:000270421100004 PM 19755047 ER PT J AU Romanus, D Weiser, MR Skibber, JM Ter Veer, A Niland, JC Wilson, JL Rajput, A Wong, YN Benson, AB Shibata, S Schrag, D AF Romanus, Dorothy Weiser, Martin R. Skibber, John M. Ter Veer, Anna Niland, Joyce C. Wilson, John L. Rajput, Ashwani Wong, Yu-Ning Benson, Al B., III Shibata, Stephen Schrag, Deborah TI Concordance with NCCN Colorectal Cancer Guidelines and ASCO/NCCN Quality Measures: An NCCN Institutional Analysis SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article DE Quality measurement; quality improvement; clinical practice guidelines; colorectal cancer AB Background: The National Comprehensive Cancer Network (NCCN) Outcomes Database was created to assess concordance to evidence- and consensus-based guidelines and to measure adherence to quality measures on an ongoing basis. The Colorectal Cancer Database began in 2005 as a collaboration among 8 NCCN centers. Methods: Newly diagnosed colon and rectal cancer patients presenting to 1 of 8 NCCN centers between September 1, 2005, and May 21, 2008, were eligible for analysis of concordance with NCCN treatment guidelines for colorectal cancer and with a set of quality metrics jointly developed by ASCO and NCCN in 2007. Adherence rates were determined for each metric. Center-specific rates were benchmarked against mean concordance rates for all participating centers. Results: A total of 3443 patients were evaluable. Mean concordance rates with NCCN colorectal cancer guidelines and ASCO/NCCN quality measures were generally high (>= 90%). However, relatively low mean concordance rates were noted for adjuvant chemotherapy treatment recommendations within 9 months of diagnosis of stage II to III rectal cancer (81%), and neoadjuvant chemoradiation in clinical T4 rectal primaries (83%). These low rates of concordance seemed to be consistent across centers. Conclusions: Adherence to guidelines and quality measures is generally high at institutions participating in the NCCN colorectal cancer database. Lack of documentation, patient refusal, delayed treatment initiation, and lack of consensus about whether treatment was essential were the primary reasons for nonconcordance. Measurement of concordance and the reasons for nonconcordance enable participating centers to understand and improve their care delivery systems. (JNCCN 2009;7:895-904) C1 [Romanus, Dorothy; Schrag, Deborah] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Weiser, Martin R.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Skibber, John M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ter Veer, Anna; Niland, Joyce C.; Shibata, Stephen] City Hope Comprehens Canc Ctr, Dept Biostat, Duarte, CA USA. [Wilson, John L.] Ohio State Univ, Dept Urol, Columbus, OH 43210 USA. [Rajput, Ashwani] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Benson, Al B., III] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Chicago, IL 60611 USA. RP Schrag, D (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,SM 204, Boston, MA 02115 USA. EM deb_schrag@dfci.harvard.edu NR 13 TC 26 Z9 28 U1 0 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2009 VL 7 IS 8 BP 895 EP 904 PG 10 WC Oncology SC Oncology GA 501YR UT WOS:000270421100006 PM 19755049 ER PT J AU Fidias, P Pennell, NA Boral, AL Shapiro, GI Skarin, AT Eder, JP Kwoh, TJ Geary, RS Johnson, BE Lynch, TJ Supko, JG AF Fidias, Panos Pennell, Nathan A. Boral, Anthony L. Shapiro, Geoffrey I. Skarin, Arthur T. Eder, Joseph P., Jr. Kwoh, T. Jesse Geary, Richard S. Johnson, Bruce E. Lynch, Thomas J. Supko, Jeffrey G. TI Phase I Study of the c-raf-1 Antisense Oligonucleotide ISIS 5132 in Combination with Carboplatin and Paclitaxel in Patients with Previously Untreated, Advanced Non-small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Chemotherapy; Clinical trials; Human subjects; Pharmacokinetics ID 2 DOSE LEVELS; C-RAF KINASE; EUROPEAN-ORGANIZATION; ANTITUMOR-ACTIVITY; OVARIAN-CANCER; CGP 69846A; TRIAL; ISIS-5132; CISPLATIN; INHIBITOR AB Background: A phase I trial was performed to evaluate the administration of carboplatin/paclitaxel in combination with ISIS-5132, a phosphorothioate antisense oligodeoxynucleotide inhibitor of c-raf-1 kinase expression, in patients with advanced non-small cell lung cancer (NSCLC). Patients and Methods: Previously untreated patients with stage IIIB/IV NSCLC received ISIS 5132 by continuous intravenous infusion at 2.0 mg/kg/d for 14 days. Starting doses were paclitaxel 175 mg/m(2) and carboplatin targeting an area under the free platinum plasma concentration-time curve (AUC(fp)) of 5 mg . min/ml (dose level 1). The carboplatin dose was then increased to AUC(fp) 6 mg . min/ml (dose level 2) after which the paclitaxel dose was increased to 200 mg/m(2) (dose level 3). The maximum tolerated dose was established by toxicity during the first two 21-day cycles of therapy. The pharmacokinetics of all three agents was determined before and during the ISIS 5132 infusion. Results: Thirteen patients were treated with the carboplatin/paclitaxel/ISIS 5132 combination. Dose-limiting neutropenia occurred in two patients. at dose level 3. Grade 3 and 4 nonhematologic toxicities were infrequent and limited to nausea and constipation. The maximum tolerated doses were carboplatin AUC(fp) 6 mg . min/ml, paclitaxel 175 mg/m(2), and ISIS 5132 2.0 mg/kg/d for 14 days. There were no objective responses and the concurrent infusion of ISIS 5132 did not alter the plasma pharmacokinetics of paclitaxel or total platinum. Conclusion: ISIS 5132 can be safely combined with standard doses of carboplatin and paclitaxel. Combining cytotoxic chemotherapeutic agents with inhibitors of aberrant signal transduction mediated by Raf proteins produced no objective responses in the dose and schedule administered in this study. C1 [Fidias, Panos; Pennell, Nathan A.; Boral, Anthony L.; Lynch, Thomas J.; Supko, Jeffrey G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shapiro, Geoffrey I.; Skarin, Arthur T.; Eder, Joseph P., Jr.; Johnson, Bruce E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. [Shapiro, Geoffrey I.; Skarin, Arthur T.; Eder, Joseph P., Jr.; Johnson, Bruce E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02114 USA. [Kwoh, T. Jesse; Geary, Richard S.] ISIS Pharmaceut, Carlsbad, CA 92008 USA. RP Fidias, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM pfidias2@partners.org FU ISIS Pharmaceuticals FX Supported by ISIS Pharmaceuticals. NR 47 TC 11 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP 1156 EP 1162 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490IX UT WOS:000269495500015 PM 19704336 ER PT J AU Sequist, LV Fidias, P Heist, RS Ostler, P Muzikansky, A Lynch, TJ AF Sequist, Lecia V. Fidias, Panos Heist, Rebecca S. Ostler, Patricia Muzikansky, Alona Lynch, Thomas J. TI Brief Report of Biweekly Pemetrexed and Gemcitabine in Elderly Patients with Non-small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Non-small cell lung cancer; Elderly; Pemetrexed; Gemcitabine ID FRONT-LINE THERAPY; PHASE-II TRIAL; CHEMOTHERAPY; VINORELBINE; COMBINATION; PACLITAXEL; AGENT AB We examined a nonplatinum-based doublet chemotherapy regimen, pemetrexed and gemicitabine given on a biweekly (every 14 days) schedule, in patients older than 70 years with newly diagnosed advanced non-small cell lung cancer. The study was closed after nine patients were treated due to excess toxicity, primarily fatigue, and nonneutropenic infection. No responses were observed. Eight of the nine patients were hospitalized during therapy and seven discontinued treatment for reasons other than progressive disease. Median progression-free survival was 1.7 months, and median overall survival was 3.9 months. We found that biweekly pemetrexed and gemcitabine was too toxic in our cohort of elderly patients with newly diagnosed advanced non-small cell lung cancer. C1 [Sequist, Lecia V.; Fidias, Panos; Heist, Rebecca S.; Ostler, Patricia] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Sequist, Lecia V.; Fidias, Panos; Heist, Rebecca S.; Ostler, Patricia; Muzikansky, Alona] Harvard Univ, Sch Med, Boston, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Lynch, Thomas J.] Yale Canc Ctr, New Haven, CT USA. [Lynch, Thomas J.] Yale Univ, Sch Med, New Haven, CT USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,POB 212, Boston, MA 02114 USA. EM lvsequist@partners.org FU Eli Lilly and Company; Elsa U. Pardee Foundation FX The authors thank the patients who participated in this study and Elizabeth Kennedy for data management. NR 15 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP 1170 EP 1173 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490IX UT WOS:000269495500017 PM 19704338 ER PT J AU Banerji, S Luo, B Barretina, J Root, D Meyerson, M AF Banerji, Shantanu Luo, Biao Barretina, Jordi Root, David Meyerson, Matthew TI Characterization of Genomic Alterations in Small Cell Lung Cancer Using Pooled RNAi Library Screens and Single-Template DNA Sequencing SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Banerji, Shantanu; Barretina, Jordi; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Banerji, Shantanu; Luo, Biao; Barretina, Jordi; Root, David; Meyerson, Matthew] Broad Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 SEP PY 2009 VL 4 IS 9 BP S806 EP S807 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002428 ER PT J AU Besse, B Suk Heist, R Papadimitrakopoulou, VA Camidge, DR Beck, JT Schmid, P Mulatero, C Pylvaenaeinen, I Petrovic, K Johnson, BE AF Besse, Benjamin Suk Heist, Rebecca Papadimitrakopoulou, Vasiliki A. Camidge, D. Ross Beck, J. Thaddeus Schmid, Peter Mulatero, Clive Pylvaenaeinen, Ilona Petrovic, Katarina Johnson, Bruce E. TI Phase I dose-escalation study investigating RAD001 (R) in combination with cisplatin (C) and etoposide (E) in previously untreated patients with extensive-stage disease small-cell lung cancer (ED-SCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Besse, Benjamin] Inst Gustave Roussy, Villejuif, France. [Suk Heist, Rebecca] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Papadimitrakopoulou, Vasiliki A.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Camidge, D. Ross] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Beck, J. Thaddeus] Highlands Oncol Grp, Fayetteville, AR USA. [Schmid, Peter] Hammersmith Hosp, London, England. [Mulatero, Clive] Leicester Royal Infirm, Leicester, Leics, England. [Pylvaenaeinen, Ilona; Petrovic, Katarina] Novartis Pharma AG, Basel, Switzerland. [Johnson, Bruce E.] Dana Farber Canc Inst, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S463 EP S464 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001290 ER PT J AU Cambpell, TC Dubenski, LL Gustafson, D Buss, MK Carmack-Taylor, CL Namkoong, K Traynor, AM Govindan, R Bhattacharya, A McTavish, F Cleary, JF AF Cambpell, Toby C. Dubenski, Lori L. Gustafson, David Buss, Mary K. Carmack-Taylor, Cindy L. Namkoong, Kang Traynor, Anne M. Govindan, R. Bhattacharya, Abhik McTavish, Fiona Cleary, James F. TI Impact of the comprehensive health enhancement support system (CHESS), an interactive cancer communication system (ICCS) on NSCLC survival: a randomized study comparing CHESS with the internet SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Cambpell, Toby C.; Dubenski, Lori L.; Gustafson, David; Namkoong, Kang; Traynor, Anne M.; Bhattacharya, Abhik; McTavish, Fiona; Cleary, James F.] Univ Wisconsin, Madison, WI USA. [Buss, Mary K.] Dana Farber Canc Ctr, Boston, MA USA. [Carmack-Taylor, Cindy L.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Govindan, R.] Washington Univ, St Louis, MO 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S369 EP S370 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001111 ER PT J AU Campling, BG Collins, BN Algazy, KM Schnoll, RA Lam, M AF Campling, Barbara G. Collins, Bradley N. Algazy, Kenneth M. Schnoll, Robert A. Lam, Miu TI Smoking cessation prior to diagnosis of lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Campling, Barbara G.; Algazy, Kenneth M.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Collins, Bradley N.] Temple Univ, Philadelphia, PA 19122 USA. [Schnoll, Robert A.] Univ Penn, Philadelphia, PA 19104 USA. [Lam, Miu] Queens Univ, Kingston, ON, Canada. 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S307 EP S308 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000321 ER PT J AU Choi, NC Gansemer, C Yock, AD Vrancic, C Bortfeld, T Trofimov, A AF Choi, Noah C. Gansemer, Cornelia Yock, Adam D. Vrancic, Christian Bortfeld, Thomas Trofimov, Alexie TI Dose ventilation-weighted and density-weighted volume histogram using 4DCT data, a new model for risk assessment of pneumonitis in thoracic radiotherapy SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Choi, Noah C.; Gansemer, Cornelia; Yock, Adam D.; Vrancic, Christian; Bortfeld, Thomas; Trofimov, Alexie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S941 EP S941 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002726 ER PT J AU Choi, NC AF Choi, Noah C. TI What is the role of adjuvant radiation therapy in resected N2 non-small cell lung cancer patients? Con. SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract ID VINORELBINE PLUS CISPLATIN; TRIALIST ASSOCIATION ANITA; POSTOPERATIVE RADIOTHERAPY; STAGE-II; RANDOMIZED-TRIAL; CHEMOTHERAPY; METAANALYSIS; SURVIVAL C1 [Choi, Noah C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S140 EP S142 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000131 ER PT J AU Chu, Q Gandhi, L Stephenson, J Johnson, BE Govindan, R Bradford, D Bonomi, P Ellison, D Eaton, K Fritsch, H Munzert, G Socinski, M AF Chu, Quincy Gandhi, Leena Stephenson, Joe Johnson, Bruce E. Govindan, Rawasmamy Bradford, Daniel Bonomi, Phil Ellison, David Eaton, Keith Fritsch, Holger Munzert, Gerd Socinski, Mark TI An open-label Phase II trial of the Plk1 inhibitor BI 2536, in patients with sensitive relapse small cell lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Chu, Quincy; Johnson, Bruce E.] Univ Alberta, Edmonton, AL USA. [Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stephenson, Joe; Govindan, Rawasmamy] Canc Ctr Carolinas, Greenville, SC USA. Washington Sch Med, St Louis, MO USA. [Bradford, Daniel] Highlands Oncol Grp, Fayetteville, AR USA. [Bonomi, Phil] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Ellison, David] Charleston Hematol Oncol, Charleston, SC USA. [Eaton, Keith] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Fritsch, Holger; Munzert, Gerd] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany. [Socinski, Mark] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 SEP PY 2009 VL 4 IS 9 BP S811 EP S812 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002439 ER PT J AU Cortot, AB Duruisseaux, M Arpin, D Perrot, E Geriniere, L Perol, M Souquet, PJ AF Cortot, Alexis B. Duruisseaux, Michael Arpin, Dominique Perrot, Emilie Geriniere, Laurence Perol, Maurice Souquet, Pierre-Jean TI Heterogeneity of response to tyrosine kinase inhibitors between primary tumors and matched metastases in Non-Small-Cell Lung Cancers SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Cortot, Alexis B.; Duruisseaux, Michael; Perrot, Emilie; Geriniere, Laurence; Souquet, Pierre-Jean] Ctr Hosp Lyon Sud, Dept Pulm Dis, Lyon, France. [Arpin, Dominique; Perol, Maurice] Hop Croix Rousse, Dept Pulm Dis, F-69317 Lyon, France. [Cortot, Alexis B.] Int Agcy Res Canc, F-69372 Lyon, France. 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S675 EP S675 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002135 ER PT J AU Dubinett, SM Hazra, S Krysan, K Al-Shyoukh, I Feng, JY Walser, T Heinrich, E Dohadwala, M Minna, JD Shay, JW Cui, XY Yanagawa, J Lee, JM Horvath, S Gardner, B Ho, CM Sharma, S Ren, S AF Dubinett, Steven M. Hazra, Saswati Krysan, Kostyantyn Al-Shyoukh, Ibrahim Feng, Jiaying Walser, Tonya Heinrich, Eileen Dohadwala, Miriam Minna, John D. Shay, Jerry W. Cui, Xiaoyan Yanagawa, Jane Lee, Jay M. Horvath, Steve Gardner, Brian Ho, Chih-Ming Sharma, Sherven Sun, Ren TI New avenues for chemoprevention: a new paradigm to identify and personalize targeted combination chemoprevention for lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Dubinett, Steven M.; Hazra, Saswati; Krysan, Kostyantyn; Walser, Tonya; Heinrich, Eileen; Dohadwala, Miriam; Cui, Xiaoyan; Yanagawa, Jane; Lee, Jay M.; Gardner, Brian; Sharma, Sherven] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90024 USA. [Dubinett, Steven M.; Hazra, Saswati; Krysan, Kostyantyn; Walser, Tonya; Dohadwala, Miriam; Cui, Xiaoyan; Yanagawa, Jane; Gardner, Brian; Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Dubinett, Steven M.; Heinrich, Eileen] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Al-Shyoukh, Ibrahim; Feng, Jiaying; Sun, Ren] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Lee, Jay M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Thorac Surg, Los Angeles, CA 90095 USA. [Horvath, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Horvath, Steve] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Ho, Chih-Ming] Univ Calif Los Angeles, Dept Mech & Aerosp Engn, Henry Sameuli Sch Engn & Appl Sci, Los Angeles, CA 90024 USA. [Dohadwala, Miriam; Cui, Xiaoyan; Sharma, Sherven] VA Greater Los Angeles Hlth Care Ctr, Los Angeles, CA USA. [Minna, John D.] VA Greater Los Angeles Hlth Care Ctr, Dallas, TX USA. [Minna, John D.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Minna, John D.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. [Shay, Jerry W.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. RI Shay, Jerry/F-7878-2011 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S137 EP S139 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000129 ER PT J AU Feser, WJ Baron, AE Wolf, HJ Jayaprakash, V Reid, M Keith, RL Kennedy, TC Hirsch, FR Franklin, WA Miller, YE Byers, T AF Feser, William J. Baron, Anna E. Wolf, Holly J. Jayaprakash, Vijay Reid, Mary Keith, Robert L. Kennedy, Timothy C. Hirsch, Fred R. Franklin, Wilbur A. Miller, York E. Byers, Tim TI Analysis of bronchial histology and incident lung cancer - a prospective approach SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Univ Colorado, Ctr Canc, Aurora, CO USA. [Feser, William J.; Baron, Anna E.; Wolf, Holly J.; Byers, Tim] Univ Colorado Denver, Sch Publ Hlth, Aurora, CO USA. [Jayaprakash, Vijay; Reid, Mary] Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. [Keith, Robert L.; Miller, York E.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Keith, Robert L.; Kennedy, Timothy C.; Hirsch, Fred R.; Miller, York E.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Hirsch, Fred R.; Franklin, Wilbur A.] Univ Colorado Denver, Dept Pathol, Aurora, CO 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S490 EP S491 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001346 ER PT J AU Gandhi, L Camidge, DR de Oliveira, MR Bonomi, PD Gandara, D Chiu, YL Xiong, H Enschede, SH Krivoshik, AP Rudin, CM AF Gandhi, Leena Camidge, David R. de Oliveira, Moacyr R. Bonomi, Philip D. Gandara, David Chiu Yi-Lin Xiong, Hao Enschede, Sari H. Krivoshik, Andrew P. Rudin, Charles M. TI A phase 1 study of ABT-263 in patients with relapsed small cell lung cancer (SCLC) and other solid tumors SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. [Camidge, David R.] Univ Colorado, Denver, CO 80202 USA. [de Oliveira, Moacyr R.] PLLC, NW Med Specialties, Tacoma, WA USA. [Bonomi, Philip D.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Gandara, David] UC Davis Canc Ctr, Sacramento, CA USA. [Chiu Yi-Lin; Xiong, Hao; Enschede, Sari H.; Krivoshik, Andrew P.] Abbott Labs, Abbott Pk, IL 60064 USA. [Rudin, Charles M.] Johns Hopkins Univ, Baltimore, MD 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S394 EP S394 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001157 ER PT J AU Hatoum, HT Lin, SJ Lipton, A Guo, A Smith, MR AF Hatoum, Hind T. Lin, Swu-Jane Lipton, Allan Guo, Amy Smith, Matthew R. TI Persistence on monthly zoledronic acid impacts risk and frequency of skeletal complications and follow-up duration in lung cancer patients SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Hatoum, Hind T.; Lin, Swu-Jane] Hind T Hatoum & Co, Chicago, IL USA. [Hatoum, Hind T.; Lin, Swu-Jane] Univ Illinois, Chicago, IL USA. [Lipton, Allan] Hershey Med Ctr, Hershey, PA USA. [Guo, Amy] Novartis Pharmaceut, Florham Pk, NJ USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S432 EP S433 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001228 ER PT J AU Herbst, RS Sun, Y Korfee, S Germonpre, P Saijo, N Zhou, C Wang, J Langmuir, P Tada, H Kennedy, SJ Johnson, BE AF Herbst, Roy S. Sun, Yan Korfee, Soenke Germonpre, Paul Saijo, Nagahiro Zhou, Caichun Wang, Jie Langmuir, Peter Tada, Hiroomi Kennedy, Sarah J. Johnson, Bruce E. TI Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced NSCLC: a randomized, double-blind phase III trial (ZODIAC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Herbst, Roy S.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Sun, Yan] Canc Hosp, Beijing, Peoples R China. [Korfee, Soenke] Univ Duisburg Essen, W German Tumor Ctr, Dept Med Canc Res, Essen, Germany. [Germonpre, Paul] Univ Antwerp Hosp, Antwerp, Belgium. [Saijo, Nagahiro] East Hosp, Natl Canc Ctr, Chiba, Japan. [Zhou, Caichun] Tongji Univ, Shanghai 200092, Peoples R China. [Wang, Jie] Beijing Inst Canc Res, Beijing, Peoples R China. [Langmuir, Peter; Tada, Hiroomi] AstraZeneca, Wilmington, DE USA. [Kennedy, Sarah J.] AstraZeneca, Macclesfield, Cheshire, England. [Johnson, Bruce E.] Dana Farber Canc Inst, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S357 EP S358 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001089 ER PT J AU Hoang, T Dahlberg, S Schiller, JH Johnson, DH AF Hoang, Tien Dahlberg, Suzanne Schiller, Joan H. Johnson, David H. TI Does histology predict survival of advanced non-small cell lung cancer (NSCLC) treated with standard platin-based chemotherapy? Retrospective analysis of E1594 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Hoang, Tien] Univ Wisconsin, Madison, WI USA. [Dahlberg, Suzanne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Johnson, David H.] Vanderbilt Univ, Nashville, TN USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S493 EP S494 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001351 ER PT J AU Hudish, TM Keith, RL Byers, T Levinson, AH Bucher-Bartelson, B Merrick, DT Franklin, WA AF Hudish, Tyler M. Keith, Robert L. Byers, Tim Levinson, Arnold H. Bucher-Bartelson, Becki Merrick, Daniel T. Franklin, Wilbur A. TI Prognostic sgnificance of biomarkers in lung tumors of patients with NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Hudish, Tyler M.; Keith, Robert L.; Merrick, Daniel T.] Denver VA Med Ctr, Denver, CO USA. [Byers, Tim] Colorado Sch Publ Hlth, Aurora, CO USA. [Levinson, Arnold H.] Univ Colorado, Denver Canc Ctr, Aurora, CO USA. [Bucher-Bartelson, Becki] Colorado Prevent Ctr, Denver, CO USA. [Franklin, Wilbur A.] Univ Colorado, Denver & Hlth Sci Ctr, Aurora, CO USA. RI Levinson, Arnold/L-3274-2013 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S910 EP S911 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002660 ER PT J AU Hudish, TM Mozer, AB Opincariu, LI Boten, JA Crossno, JT Keith, RL AF Hudish, Tyler M. Mozer, Anthony B. Opincariu, Laura, I Boten, Jessica A. Crossno, Joseph T. Keith, Robert L. TI The effects of multiple COX pathway manipulations on murine lung tumorigenesis SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Hudish, Tyler M.; Mozer, Anthony B.; Opincariu, Laura, I; Boten, Jessica A.; Crossno, Joseph T.; Keith, Robert L.] Denver VA Med Ctr, Denver, CO 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S869 EP S870 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002570 ER PT J AU Jackman, DM Kesari, S Cioffredi, LA Sequist, LV Rabin, MS Lynch, TJ Marcoux, JP Johnson, BE AF Jackman, David M. Kesari, Santosh Cioffredi, Leigh-Anne Sequist, Lecia V. Rabin, Michael S. Lynch, Thomas J. Marcoux, J. P. Johnson, Bruce E. TI Phase I study of high dose gefitinib in patients with leptomeningeal metastases from EGFR-mutant non-small cell lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Jackman, David M.; Kesari, Santosh; Cioffredi, Leigh-Anne; Rabin, Michael S.; Marcoux, J. P.; Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sequist, Lecia V.; Lynch, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 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 SEP PY 2009 VL 4 IS 9 BP S685 EP S685 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002157 ER PT J AU Jackman, DM Miller, VA Cioffredi, LA Yeap, BY Janne, PA Riely, GJ Ruiz, MG Giaccone, G Sequist, LV Johnson, BE AF Jackman, David M. Miller, Vincent A. Cioffredi, Leigh-Anne Yeap, Beow Y. Janne, Pasi A. Riely, Gregory J. Ruiz, Gallegos Marielle Giaccone, Giuseppe Sequist, Lecia, V Johnson, Bruce E. TI Impact of EGFR and KRAS mutations on clinical outcomes in previously untreated patients with advanced NSCLC treated with gefitinib or erlotinib: results of an online tumor registry of clinical trials SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Jackman, David M.; Cioffredi, Leigh-Anne; Janne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miller, Vincent A.; Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Yeap, Beow Y.; Sequist, Lecia, V] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ruiz, Gallegos Marielle] Vrije Univ Amsterdam, Amsterdam, Netherlands. [Giaccone, Giuseppe] NCI, Bethesda, MD 20892 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S349 EP S350 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001075 ER PT J AU Jackman, DM Cioffredi, LA Lindeman, NI Morse, LK Lucca, J Weckstein, D Huberman, MS Lynch, TJ Johnson, BB Janne, PA AF Jackman, David M. Cioffredi, Leigh-Anne Lindeman, Neal, I Morse, Linda K. Lucca, Joan Weckstein, Doug Huberman, Mark S. Lynch, Thomas J. Johnson, Bruce B. Janne, Pasi A. TI Final results of a phase II trial of erlotinib in chemo-naive women with advanced pulmonary adenocarcinoma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Jackman, David M.; Cioffredi, Leigh-Anne; Morse, Linda K.; Lucca, Joan; Johnson, Bruce B.; Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lindeman, Neal, I] Brigham & Womens Hosp, Boston, MA 02115 USA. [Weckstein, Doug] Dana Farber New Hampshire Oncol Hematol, Londonderry, NH USA. [Lynch, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Huberman, Mark S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S295 EP S295 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000297 ER PT J AU Janne, PA Reckamp, K Koczywas, M Camidge, DR Engelman, JA Khuri, F Rajan, A Gadgeel, S Taylor, I Liang, J O'Connell, J Giaccone, G AF Janne, Pasi A. Reckamp, Karen Koczywas, Marianna Camidge, David R. Engelman, Jeffery A. Khuri, Fadlo Rajan, Arun Gadgeel, Shirish Taylor, Ian Liang, Jane O'Connell, Joseph Giaccone, Giuseppe TI A phase 2 trial of PF-00299804 (PF299), an oral irreversible HER tyrosine kinase inhibitor (TKI), in patients (pts) with advanced NSCLC after failure of prior chemotherapy and erlotinib: preliminary efficacy and safety results SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Taylor, Ian; Liang, Jane; O'Connell, Joseph] Pfizer Global Res & Dev, New London, CT USA. [Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Reckamp, Karen; Koczywas, Marianna] City Hope Natl Med Ctr, Duarte, CA USA. [Engelman, Jeffery A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Camidge, David R.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Rajan, Arun; Giaccone, Giuseppe] NCI, Bethesda, MD 20892 USA. [Khuri, Fadlo] Emory Univ, Sch Med, Winship Canc Ctr, Atlanta, GA 30322 USA. [Gadgeel, Shirish] Karmanos Canc Inst, Troy, MI USA. NR 0 TC 12 Z9 12 U1 1 U2 1 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 SEP PY 2009 VL 4 IS 9 BP S293 EP S294 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000294 ER PT J AU Karoor, V Le, M Miller, YE AF Karoor, Vijaya Le, Mysan Miller, York E. TI Alveolar hypoxia acts as a tumor promoter for murine lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Karoor, Vijaya; Miller, York E.] Univ Colorado, Denver, CO 80202 USA. [Le, Mysan] Denver VAMC, Denver, CO 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S386 EP S386 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001142 ER PT J AU Keith, RL Kittelson, JK Blatchford, PJ Jackson, M Franklin, WA Hirsch, FR Minna, J Bunn, PA Miller, YE AF Keith, Robert L. Kittelson, John K. Blatchford, Patrick J. Jackson, Mary Franklin, Wilbur A. Hirsch, Fred R. Minna, John Bunn, Paul A. Miller, York E. TI Oral iloprost improves endobronchial dysplasia in former smokers SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Keith, Robert L.; Miller, York E.] UC Denver, Denver VAMC, Denver, CO USA. [Kittelson, John K.; Blatchford, Patrick J.] Univ Colorado, Sch Publ Hlth, Aurora, CO USA. [Keith, Robert L.; Jackson, Mary; Franklin, Wilbur A.; Hirsch, Fred R.; Bunn, Paul A.; Miller, York E.] Univ Colorado, Ctr Comprehens Canc, Aurora, CO USA. [Franklin, Wilbur A.] Univ Colorado, Dept Pathol, Denver, CO 80202 USA. [Minna, John] Univ Texas SW, Hamon Ctr Therapeut Oncol, Dallas, TX 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S380 EP S380 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001131 ER PT J AU Keith, RL AF Keith, Robert L. TI Oral iloprost for the chemoprevention of lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Keith, Robert L.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Keith, Robert L.] Univ Colorado, Ctr Comprehens Canc, Denver, CO 80202 USA. [Keith, Robert L.] Univ Colorado, Div Pulm Sci & Crit Care Med, Denver, CO 80202 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S135 EP S136 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000126 ER PT J AU Merrick, DT Lewis, MT Franklin, WA Miller, YE Keith, RL Kennedy, TC Blatchford, P Baron, AE Chesnut, P Hirsch, FR AF Merrick, Daniel T. Lewis, Marina T. Franklin, Wilbur A. Miller, York E. Keith, Robert L. Kennedy, Tim C. Blatchford, Patrick Baron, Anna E. Chesnut, Partrick Hirsch, Fred R. TI Correlation of baseline Ki67 expression with degree of atypia on rebiopsy in normal and dysplastic bronchial mucosa SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Merrick, Daniel T.; Miller, York E.; Keith, Robert L.] Univ Colorado, Hlth Sci Ctr, Denver VAMC, Denver, CO USA. [Lewis, Marina T.; Franklin, Wilbur A.; Kennedy, Tim C.; Blatchford, Patrick; Baron, Anna E.; Chesnut, Partrick; Hirsch, Fred R.] Univ Colorado, Ctr Canc, Denver, CO 80262 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S514 EP S514 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001391 ER PT J AU Meyerson, M AF Meyerson, Matthew TI Oncogene discovery in lung adenocarcinoma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Cambridge, MA 02138 USA. [Meyerson, Matthew] Broad Inst Harvard & MIT, Cambridge, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S147 EP S147 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000136 ER PT J AU Miller, YE Keith, RL AF Miller, York E. Keith, Robert L. TI Chemoprevention: EGFR targeted agents SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Miller, York E.; Keith, Robert L.] Univ Colorado, Ctr Canc, Denver Vet Affairs Med Ctr, Denver, CO 80262 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S190 EP S190 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000187 ER PT J AU Neal, JW Woytowitz, D Patel, T Dreisbach, L McCleod, M Heim, WJ Weber, MR Siegel, J Gustafson, N Lynch, TJ AF Neal, Joel W. Woytowitz, Donald Patel, Taral Dreisbach, Luke McCleod, Mitcehll Heim, William J. Weber, Martin R. Siegel, Jonathan Gustafson, Nancy Lynch, Thomas J. TI Skin rash as a surrogate marker of cetuximab efficacy in advanced NSCLC: a retrospective analysis of BMS099 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Neal, Joel W.; Lynch, Thomas J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Woytowitz, Donald; McCleod, Mitcehll] Florida Canc Specialists, Ft Myers, FL USA. [Patel, Taral] Mid Ohio Oncol Hematol Inc, Columbus, OH USA. [Dreisbach, Luke] Desert Hematol Oncol Med Grp, Rancho Mirage, CA USA. [Heim, William J.] Hematol & Oncol Associates NE Penn, Dunmore, PA USA. [Weber, Martin R.; Siegel, Jonathan; Gustafson, Nancy] Bristol Myers Squibb Co, Wallingford, CT 06492 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S534 EP S534 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001430 ER PT J AU Opincariu, LI Hudish, TM Merrick, D Malkoski, S Cleaver, T Mozer, AB Keith, RL AF Opincariu, Laura, I Hudish, Tyler M. Merrick, Daniel Malkoski, Stephen Cleaver, Tim Mozer, Anthony B. Keith, Robert L. TI Characterization of pre-malignant dysplasia and squamous cell carcinoma in the NTCU-induced murine model SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Opincariu, Laura, I; Hudish, Tyler M.; Merrick, Daniel; Mozer, Anthony B.; Keith, Robert L.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Malkoski, Stephen; Cleaver, Tim; Keith, Robert L.] Univ Colorado, Hlth Sci Ctr, Aurora, CO 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S632 EP S633 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002039 ER PT J AU Ostroff, RM Brody, EN Zichi, DA Miller, Y Wolf, H Franklin, W AF Ostroff, Rachel M. Brody, Edward N. Zichi, Dom A. Miller, York Wolf, Holly Franklin, Wilbur TI Highly multiplexed SLaptamer-based proteomics technology discovers biomarkers in plasma for the detection of lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Ostroff, Rachel M.; Brody, Edward N.; Zichi, Dom A.] SomaLogic Inc, Boulder, CO USA. [Miller, York] Univ Colorado, Ctr Canc, Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. [Wolf, Holly] Univ Colorado, Ctr Canc, Colorado Sch Publ Hlth, Denver, CO 80262 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S511 EP S511 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001385 ER PT J AU Richards, WG Godleski, JJ Yeap, BY Corson, JM Chirieac, LR Jaklitsch, MT Bueno, R Sugarbaker, DJ AF Richards, William G. Godleski, John J. Yeap, Beow Y. Corson, Joseph M. Chirieac, Lician R. Jaklitsch, Michael T. Bueno, Raphael Sugarbaker, David J. TI Pathologic staging of biphasic mesothelioma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Richards, William G.; Godleski, John J.; Corson, Joseph M.; Chirieac, Lician R.; Jaklitsch, Michael T.; Bueno, Raphael; Sugarbaker, David J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yeap, Beow Y.] 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S773 EP S773 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002350 ER PT J AU Schiller, J Lee, JW Hanna, NH Traynor, AM Wakelee, H Carbone, DP AF Schiller, Joan Lee, Ju-whei Hanna, Nasser H. Traynor, Anne M. Wakelee, Heather Carbone, David P. TI A randomized discontinuation phase II study of sorafenib vs placebo in patients with non-small cell lung cancer (NSCLC) who failed at least two prior chemotherapy regimens: E2501 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Schiller, Joan] UT Southwestern, Dallas, TX USA. [Carbone, David P.] Vanderbilt Univ, Ctr Canc, Nashville, TN USA. [Hanna, Nasser H.] Indiana Univ, Indianapolis, IN 46204 USA. [Traynor, Anne M.] Univ Wisconsin, Madison, WI USA. [Wakelee, Heather] Stanford Univ, Stamford, CT USA. [Lee, Ju-whei] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S355 EP S356 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001086 ER PT J AU Sequist, LV Sharma, SV Supko, JG Neal, JW Fidias, P Temel, J Heist, RS Shaw, AT Engelman, JA Settleman, JE Lynch, TJ AF Sequist, Lecia, V Sharma, Sreenath, V Supko, Jeffrey G. Neal, Joel W. Fidias, Panos Temel, Jennifer Heist, Suk Rebecca Shaw, Alice T. Engelman, Jeffrey A. Settleman, Jeffrey E. Lynch, Thomas J. TI Phase I study of erlotinib and hydroxychloroquine in non-small cell lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Sequist, Lecia, V; Sharma, Sreenath, V; Supko, Jeffrey G.; Neal, Joel W.; Fidias, Panos; Temel, Jennifer; Heist, Suk Rebecca; Shaw, Alice T.; Engelman, Jeffrey A.; Settleman, Jeffrey E.; Lynch, Thomas J.] 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S712 EP S713 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002217 ER PT J AU Shaw, AT Costa, DB Iafrate, AJ Dezube, BJ Shapiro, GI Bang, YJ Janne, PA Lynch, TJ Maki, RG Camidge, DR Solomon, B Kwak, EL Tan, WW Chen, I Christensen, J Wilner, K Clark, JW Salgia, R AF Shaw, Alice T. Costa, Daniel B. Iafrate, A. J. Dezube, Bruce J. Shapiro, Geoffrey, I Bang, Yung J. Janne, Pasi A. Lynch, Thomas J. Maki, Robert G. Camidge, D. R. Solomon, Benjamin Kwak, Eunice L. Tan, Weiwei Chen, Isan Christensen, Jamie Wilner, Keith Clark, Jeffrey W. Salgia, Ravi TI Clinical activity of the oral ALK and MET inhibitor PF-02341066 in non-small lung cancer (NSCLC) with EML4-ALK translocations SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Costa, Daniel B.; Dezube, Bruce J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Shaw, Alice T.; Iafrate, A. J.; Lynch, Thomas J.; Kwak, Eunice L.; Clark, Jeffrey W.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Camidge, D. R.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Shapiro, Geoffrey, I; Janne, Pasi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Maki, Robert G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Solomon, Benjamin] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Bang, Yung J.] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Salgia, Ravi] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Wilner, Keith] Pfizer Pharmaceut Inc, La Jolla, CA USA. [Tan, Weiwei; Chen, Isan; Christensen, Jamie] Pfizer Inc, La Jolla, CA USA. NR 0 TC 11 Z9 12 U1 0 U2 5 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 SEP PY 2009 VL 4 IS 9 BP S305 EP S306 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000317 ER PT J AU Soejima, K Nakayama, S Yasuda, H Watanabe, H Kawada, I Nakachi, I Yoda, S Satomi, R Ikemura, S Terai, H Naoki, K Ishizaka, A AF Soejima, Kenzo Nakayama, Sohei Yasuda, Hiroyuki Watanabe, Hideo Kawada, Ichiro Nakachi, Ichiro Yoda, Satoshi Satomi, Ryosuke Ikemura, Shinnosuke Terai, Hideki Naoki, Katsuhiko Ishizaka, Akitoshi TI Bronchoscopic microsampling is a useful complementary diagnostic tool for lung cancer patients SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Soejima, Kenzo; Nakayama, Sohei; Yasuda, Hiroyuki; Yoda, Satoshi; Satomi, Ryosuke; Ikemura, Shinnosuke; Terai, Hideki; Naoki, Katsuhiko; Ishizaka, Akitoshi] Keio Univ, Sch Med, Shinjuku Ku, Tokyo, Japan. [Watanabe, Hideo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kawada, Ichiro] Hino Municipal Hosp, Tokyo, Japan. [Nakachi, Ichiro] Saiseikai Utsunomiya Hosp, Utsunomiya, Tochigi, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S471 EP S472 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001307 ER PT J AU Su, L Zhai, RH Lynch, T Wain, J Asomaning, K Lin, XH Christiani, DC Chen, F Shen, CC Tejera, P AF Su Li Zhai Rihong Lynch, Thomas Wain, John Asomaning, Kofi Lin Xihong Christiani, David C. Chen Feng Shen Chau-Chyun Tejera, Paula TI Polymorphisms in the AKAP9, SEZ6L, and CAMKK1 genes are not significantly associated with lung cancer risk in a population of Caucasians SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Su Li; Zhai Rihong; Asomaning, Kofi; Lin Xihong; Christiani, David C.; Chen Feng; Shen Chau-Chyun; Tejera, Paula] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lynch, Thomas; Wain, John] 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S420 EP S420 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001203 ER PT J AU Thatcher, N Lynch, TJ Butts, C Rosell, R Shepherd, F Pujol, JL Vansteenkiste, J Emig, M Groos, J Pirker, R AF Thatcher, Nick Lynch, Thomas J. Butts, Charles Rosell, Rafael Shepherd, Frances Pujol, Jean-Louis Vansteenkiste, Johan Emig, Michael Groos, Jutta Pirker, Robert TI Cetuximab plus platinum-based chemotherapy as 1st-line treatment in patients with non-small cell lung cancer (NSCLC): a meta-analysis of randomized phase II/III trials SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Thatcher, Nick] Christie Hosp NHS Fdn Trust, Manchester, Lancs, England. [Lynch, Thomas J.] Massachusetts Gen Hosp, Yawkey Canc Ctr, Boston, MA USA. [Butts, Charles] Cross Canc Inst, Edmonton, AB, Canada. [Rosell, Rafael] Hosp Germans Trias i Pujol, Catalan Inst Oncol, Barcelona, Spain. [Shepherd, Frances] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Pujol, Jean-Louis] Inst Univ Rech Clin, Montpellier, France. [Vansteenkiste, Johan] Univ Hosp Leuven, Louvain, Belgium. [Emig, Michael; Groos, Jutta] Merck KGaA, Darmstadt, Germany. [Pirker, Robert] Med Univ Vienna, Vienna, Austria. RI Vansteenkiste, Johan/B-8191-2014 OI Vansteenkiste, Johan/0000-0002-6721-2775 NR 0 TC 7 Z9 7 U1 0 U2 5 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 SEP PY 2009 VL 4 IS 9 BP S297 EP S297 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000300 ER PT J AU Travis, WD Brambilla, E Noguchi, M Geisinger, K Beer, D Powell, CA Johnson, B Riely, GJ Rusch, V Asamura, H Garg, K Austin, J Aberle, D Brambilla, C Flieder, D Franklin, W Gazdar, A Gould, M Hasleton, P Henderson, D Hirsch, F Huber, RM Ishikawa, Y Jett, J Kerr, K Johnson, D Kuriyama, K Lee, JS Miller, V Mitsudomi, T Nicholson, A Petersen, I Roggli, V Rosell, R Saijo, N Sanchez-Cespedes, M Scagliotti, G Sculier, JP Takahashi, T Thunnissen, E Tsao, M Tsuboi, M Van Schil, PE Vansteenkiste, J Yatabe, Y Wistuba, I Ynag, PC AF Travis, William D. Brambilla, Elisabeth Noguchi, Masayuki Geisinger, Kim Beer, David Powell, Charles A. Johnson, Bruce Riely, Gregory J. Rusch, Valerie Asamura, Hisao Garg, Kavita Austin, John Aberle, Denise Brambilla, Christian Flieder, Douglas Franklin, Wilbur Gazdar, Adi Gould, Michael Hasleton, Philip Henderson, Douglas Hirsch, Fred Huber, Rudolf M. Ishikawa, Yuichi Jett, James Kerr, Keith Johnson, David Kuriyama, Keiko Lee, Jin Soo Miller, Vincent Mitsudomi, Tetsuya Nicholson, Andrew Petersen, Iver Roggli, Victor Rosell, Rafael Saijo, Nagahiro Sanchez-Cespedes, Montserrat Scagliotti, Giorgio Sculier, Jean-Paul Takahashi, Takashi Thunnissen, Erik Tsao, Ming Tsuboi, Masahiro Van Schil, Paul E. Vansteenkiste, Johan Yatabe, Yasushi Wistuba, Ignacio Ynag, Pan-Chyr TI The new IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Travis, William D.; Riely, Gregory J.; Rusch, Valerie; Miller, Vincent] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Brambilla, Elisabeth; Brambilla, Christian] Univ Grenoble, Grenoble, France. [Asamura, Hisao] Natl Canc Ctr, Tokyo, Japan. [Asamura, Hisao] Res Inst, Tokyo, Japan. [Noguchi, Masayuki] Univ Tsukuba, Tsukuba, Ibaraki, Japan. [Powell, Charles A.; Austin, John] Columbia Univ, New York, NY USA. [Beer, David] Univ Michigan, Ann Arbor, MI 48109 USA. [Garg, Kavita; Franklin, Wilbur; Hirsch, Fred] Univ Colorado, Aurora, CO USA. [Johnson, Bruce] Dana Farber Canc Inst, Boston, MA 02115 USA. [Geisinger, Kim] Wake Forest Univ, Winston Salem, NC 27109 USA. [Scagliotti, Giorgio] Univ Turin, Turin, Italy. [Takahashi, Takashi] Nagoya Univ, Nagoya, Aichi 4648601, Japan. [Mitsudomi, Tetsuya; Yatabe, Yasushi] Aichi Canc Ctr, Nagoya, Aichi 464, Japan. [Nicholson, Andrew] Royal Brompton Hosp, London SW3 6LY, England. [Kerr, Keith] Aberdeen Royal Infirm, Aberdeen, Scotland. [Ishikawa, Yuichi] JFCR Canc Inst, Tokyo, Japan. [Petersen, Iver] Univ Jena, Jena, Germany. [Tsao, Ming] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Sanchez-Cespedes, Montserrat] Hosp Durant & Reynals, Barcelona, Spain. [Wistuba, Ignacio] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ynag, Pan-Chyr] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Aberle, Denise] Univ Calif Los Angeles, Los Angeles, CA USA. [Kuriyama, Keiko] Osaka Natl Hosp, Natl Hosp Org, Osaka, Japan. [Van Schil, Paul E.] Univ Antwerp Hosp, B Edegem, Belgium. Tokyo Med Univ, Kanagawa Canc Ctr, Tokyo, Japan. [Tsuboi, Masahiro] Tokyo Med Univ & Hosp, Tokyo, Japan. [Gazdar, Adi] UT SW Med Ctr, Dallas, TX USA. [Gould, Michael] Stanford Sch Med, Stanford, CA USA. [Huber, Rudolf M.] Univ Munich, Munich, Germany. [Jett, James] Mayo Clin, Rochester, MN USA. [Johnson, David] Vanderbilt Clin, Nashville, TN USA. [Lee, Jin Soo] Natl Canc Ctr, Seoul, South Korea. [Rosell, Rafael] Catalan Inst Oncol, Barcelona, Spain. [Saijo, Nagahiro] Hosp East, Natl Canc Ctr, Chiba, Japan. [Sculier, Jean-Paul] Inst Jules Bordet, B-1000 Brussels, Belgium. [Vansteenkiste, Johan] Univ Hosp Leuven, Louvain, Belgium. [Flieder, Douglas] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Thunnissen, Erik] VU Med Ctr, Amsterdam, Netherlands. [Hasleton, Philip] Univ Manchester, Manchester, Lancs, England. [Henderson, Douglas] Flinders Med Ctr, Adelaide, SA, Australia. [Roggli, Victor] Duke Univ, Durham, NC USA. RI Brambilla, Elisabeth/L-8796-2013; BRAMBILLA, CHRISTIAN/K-2285-2013; Vansteenkiste, Johan/B-8191-2014; Takahashi, Takashi/I-7262-2014 OI Vansteenkiste, Johan/0000-0002-6721-2775; NR 0 TC 6 Z9 8 U1 0 U2 4 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 SEP PY 2009 VL 4 IS 9 BP S86 EP S89 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000083 ER PT J AU West, H Lilenbaum, R Harpole, D Wozniak, A Sequist, L AF West, Howard Lilenbaum, Rogerio Harpole, David Wozniak, Antoinette Sequist, Lecia TI Molecular Analysis-Based Treatment Strategies for the Management of Non-small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Molecular biomarkers; Non-small cell lung cancer; Epidermal growth factor receptor ID GROWTH-FACTOR-RECEPTOR; PHASE-III TRIAL; CHEMOTHERAPY-NAIVE PATIENTS; SIGNATURE PREDICTS SURVIVAL; VINORELBINE PLUS CISPLATIN; TYROSINE KINASE INHIBITOR; MESSENGER-RNA EXPRESSION; ONCOLOGY-GROUP TRIAL; GROUP-STUDY BR.21; THYMIDYLATE SYNTHASE AB Even with the introduction of targeted agents and the establishment of multiple lines of therapy, the median survival for patients with advanced non-small cell lung cancer (NSCLC) does not considerably extend beyond 1 year. Emerging research suggests that clinical characteristics alone are insufficient for selecting patients for therapies that may confer significant survival benefit. The discovery of predictive and prognostic molecular markers such as gene mutations in EGFR and KRAS as well as high tumor expression levels of DNA repair pathway components ribonucleotide reductase subunit 1 and excision repair cross-complementing group l has sparked an interest in the development of individualized therapy as a strategy for increasing survival in patients with NSCLC. Techniques to analyze molecular biomarkers, such as immunohistochemistry, fluorescence in situ hybridization, polymerase chain reaction, and, more recently, gene microarray techniques, are being investigated for their potential to accurately predict an individual patient's response to therapy. Many prospective trials are still needed to clarify and confirm the utility of molecular biomarkers for guiding treatment selection, and continued participation in clinical trials is critical for the development of tools to provide customized treatment plans for patients with NSCLC. C1 [West, Howard; Lilenbaum, Rogerio] Swedish Canc Inst, Thorac Oncol Program, Seattle, WA 98104 USA. [Harpole, David] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Wozniak, Antoinette] Barbara Ann Karmanos Canc Inst, Dept Med, Detroit, MI USA. [Sequist, Lecia] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Dept Surg, Boston, MA 02114 USA. RP West, H (reprint author), Swedish Canc Inst, Thorac Oncol Program, 1221 Madison St,Suite 1020, Seattle, WA 98104 USA. EM howard.west@swedish.org RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU Genentech BioOncology/OSI Pharmaceuticals, Inc.; Lilly USA, LLC; Pfizer Oncology; Sanofi-Aventis FX The CBCE gratefully acknowledges the educational grants provided by Genentech BioOncology/OSI Pharmaceuticals, Inc.; Lilly USA, LLC; Pfizer Oncology; and Sanofi-Aventis. NR 78 TC 23 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 SU 2 BP S1029 EP S1039 PG 11 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JF UT WOS:000269496300002 PM 19704347 ER PT J AU Yu, J Kane, S Benedettini, E Li, DQ Crosby, K Wetzel, R Gu, TL Loda, M Zhou, XM Comb, M AF Yu Jian Kane, Susan Benedettini, Elisa Li Daiqiang Crosby, Katie Wetzel, Randall Gu Tinglei Loda, Massimo Zhou Xinmin Comb, Michael TI Detecting EGFR mutations in NSCLC with specific antibodies SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Yu Jian; Kane, Susan; Crosby, Katie; Wetzel, Randall; Gu Tinglei; Comb, Michael] Cell Signaling Technol Inc, Danver, MA USA. Dept Med Oncol, Boston, MA USA. Ctr Mol Oncol Pathol, Boston, MA USA. [Li Daiqiang; Zhou Xinmin] 2nd Xiangya Hosp, Changsha, Peoples R China. [Benedettini, Elisa; Loda, Massimo] Dana Farber Canc Inst, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S341 EP S342 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001060 ER PT J AU King, DR Ogilvie, MP Pereira, BMT Chang, YC Manning, RJ Conner, JA Schulman, CI McKenney, MG Proctor, KG AF King, David R. Ogilvie, Michael P. Pereira, Bruno M. T. Chang, Yuchiao Manning, Ronald J. Conner, Jeffrey A. Schulman, Carl I. McKenney, Mark G. Proctor, Kenneth G. TI Heart Rate Variability as a Triage Tool in Patients With Trauma During Prehospital Helicopter Transport SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Eastern-Association-for-the-Surgery-of-Trauma CY JAN 13-17, 2008 CL Lake Buena Vista, FL SP Eastern Assoc Surg Trauma DE Combat casualty care; Base deficit; Vital sign monitor ID BEDSIDE MONITORING STRATEGY; BRAIN-INJURY; MORTALITY; VOLATILITY; ASSOCIATION; COMPLEXITY; PREDICTOR; CHILDREN; INTERVAL; CRITERIA AB Background: Prehospital triage of patients with trauma is routinely challenging, but more so in mass casualty situations and military operations. The purpose of this study was to prospectively test whether heart rate variability (HRV) could be used as a triage tool during helicopter transport of civilian patients with trauma. Methods: After institutional review board approval and waiver of informed consent, 75 patients with trauma requiring prehospital helicopter transport to our level I center (from December 2007 to November 2008) were prospectively instrumented with a 2-Channel SEER Light recorder (GE Healthcare, Milwaukee, WI). HRV was analyzed with a Mars Holter monitor system and proprietary software. SDNN (standard deviation [SD] of the normal-to-normal R-R interval), as an index of HRV, was correlated with prehospital trauma triage criteria, base deficit, seriousness Of injury, operative interventions, outcome, and other data extracted from the patients' medical records. There were no interventions or medical decisions based on HRV. Data were excluded only if there was measurement artifact or technical problems with the recordings. Results: The demographics were mean age 47 years, 63% men, 88% blunt, 25% traumatic brain injury, 9% mortality. Prehospital SDNN predicted patients with base excess <=-6, those defined as seriously injured and benefiting front trauma center care, as well as patients requiring a life-saving procedure in the operating room. No other available data, including prehospital en-route vital signs, predicted any of these. The sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 75%, 33%, 96%, respectively, with and an overall accuracy of 76% for predicting a life-saving intervention in the operating room. Conclusions: This, is the first demonstration that prehospital HRV (specifically SDNN) predicts base excess and operating room life-saving opportunities. HRV triages and discriminates severely injured patients better than routine trauma criteria or en-route prehospital vital signs. HRV may be a useful civilian or military triage tool to avoid unnecessary helicopter evacuation for minimally injured patients. A prospective, randomized trial in a larger patient population is indicated. C1 [King, David R.; Ogilvie, Michael P.; Pereira, Bruno M. T.; Manning, Ronald J.; Conner, Jeffrey A.; Schulman, Carl I.; McKenney, Mark G.; Proctor, Kenneth G.] Univ Miami, Miller Sch Med, Daughtry Family Dept Surg, Div Trauma & Surg Crit Care, Miami, FL 33136 USA. [King, David R.; Chang, Yuchiao] Harvard Univ, Massachusetts Gen Hosp, Sch Med,,Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02141 USA. [Conner, Jeffrey A.] GE Healthcare Diagnost Cardiol, Marquette, MI USA. RP King, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,,Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambrige St,Suite 810, Boston, MA 02141 USA. EM Dking3@partners.org OI King, David/0000-0003-1028-1478 NR 33 TC 32 Z9 32 U1 0 U2 4 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 SEP PY 2009 VL 67 IS 3 BP 436 EP 440 DI 10.1097/TA.0b013e3181ad67de PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 493IL UT WOS:000269729900003 PM 19741382 ER PT J AU Pieretti-Vanmarcke, R Velmahos, GC Nance, ML Islam, S Falcone, RA Wales, PW Brown, RL Gaines, BA McKenna, C Moore, FO Goslar, PW Inaba, K Barmparas, G Scaife, ER Metzger, RR Brockmeyer, DL Upperman, JS Estrada, J Lanning, DA Rasmussen, SK Danielson, PD Hirsh, MP Consani, HFX Stylianos, S Pineda, C Norwood, SH Bruch, SW Drongowski, R Barraco, RD Pasquale, MD Hussain, F Hirsch, EF McNeely, PD Fallat, ME Foley, DS Iocono, JA Bennett, HM Waxman, K Kam, K Bakhos, L Petrovick, L Chang, YC Masiakos, PT AF Pieretti-Vanmarcke, Rafael Velmahos, George C. Nance, Michael L. Islam, Saleem Falcone, Richard A., Jr. Wales, Paul W. Brown, Rebeccah L. Gaines, Barbara A. McKenna, Christine Moore, Forrest O. Goslar, Pamela W. Inaba, Kenji Barmparas, Galinos Scaife, Eric R. Metzger, Ryan R. Brockmeyer, Douglas L. Upperman, Jeffrey S. Estrada, Joaquin Lanning, David A. Rasmussen, Sara K. Danielson, Paul D. Hirsh, Michael P. Consani, Heitor F. X. Stylianos, Steven Pineda, Candace Norwood, Scott H. Bruch, Steven W. Drongowski, Robert Barraco, Robert D. Pasquale, Michael D. Hussain, Farheen Hirsch, Erwin F. McNeely, P. Daniel Fallat, Mary E. Foley, David S. Iocono, Joseph A. Bennett, Heather M. Waxman, Kenneth Kam, Kelly Bakhos, Lisa Petrovick, Laurie Chang, Yuchiao Masiakos, Peter T. TI Clinical Clearance of the Cervical Spine in Blunt Trauma Patients Younger Than 3 Years: A Multi-Center Study of the American Association for the Surgery of Trauma SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the American-Association-for-the-Surgery-of-Trauma CY SEP 24-27, 2008 CL Maui, HI SP Amer Assoc Surg Trauma DE Pediatric trauma; Cervical spine injury; Clinical decision rules; Outcomes ID ISOLATED LIGAMENTOUS INJURY; COMPUTED-TOMOGRAPHY SCAN; EARLY WORK-UP; RADIATION-EXPOSURE; PEDIATRIC-PATIENTS; MULTIPLE INJURIES; CT; CHILDREN; CANCER; RADIOGRAPHY AB Background: Cervical spine clearance in the very young child is challenging. Radiographic imaging to diagnose cervical spine injuries (CSI) even in the absence of clinical findings is common, raising concerns about radiation exposure and imaging-related complications. We examined whether simple clinical criteria can be used to safely rule out CSI in patients younger than 3 years. Methods: The trauma registries from 22 level I or II trauma centers were reviewed for the 10-year period (January 1995 to January 2005). Blunt trauma patients younger than 3 years were identified. The measured outcome was CSI. Independent predictors of CSI were identified by univariate and multivariate analysis. A weighted score was calculated by assigning 1, 2, or 3 points to each independent predictor according to its magnitude of effect. The score was established on two thirds of the population and validated using the remaining one third. Results: Of 12,537 patients younger than 3 years, CSI was identified in 83 patients (0.66%), eight had spinal cord injury. Four independent predictors of CSI were identified: Glasgow Coma Score < 14 GCS(EYE) = 1, motor vehicle crash, and age 2 years or older. A score of <2 had a negative predictive value of 99.93% in ruling out CSI. A total of 8,707 patients (69.5% of all patients) had a score of <2 and were eligible for cervical spine clearance without imaging. There were no missed CSI in this study. Conclusions: CSI in patients younger than 3 years is uncommon. Four simple clinical predictors can be used in conjunction to the physical examination to substantially reduce the use of radiographic imaging in this patient population. C1 [Pieretti-Vanmarcke, Rafael; Masiakos, Peter T.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Bakhos, Lisa] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Epidemiol, Boston, MA 02114 USA. [Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit, Boston, MA 02114 USA. [Falcone, Richard A., Jr.; Brown, Rebeccah L.] Univ Cincinnati, Dept Surg, Cincinnati Childrens Hosp, Div Pediat & Thorac Surg,Med Ctr, Cincinnati, OH 45267 USA. [Hirsch, Erwin F.] Boston Univ, Sch Med, Dept Surg, Boston Med Ctr, Boston, MA 02118 USA. [Moore, Forrest O.] St Josephs Med Ctr, Phoenix, AZ USA. [Inaba, Kenji; Barmparas, Galinos] Univ So Calif, LAC USC Med Ctr, Dept Surg, Los Angeles, CA USA. [Upperman, Jeffrey S.; Estrada, Joaquin] Childrens Hosp Los Angeles, Dept Surg, Los Angeles, CA 90027 USA. [Wales, Paul W.] Hosp Sick Children, Dept Surg, Toronto, ON M5G 1X8, Canada. [Stylianos, Steven; Pineda, Candace] Miami Childrens Hosp, Dept Pediat Surg, Miami, FL USA. [Islam, Saleem] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Norwood, Scott H.] E Texas Med Ctr, Tyler, TX USA. [Gaines, Barbara A.; McKenna, Christine] Childrens Hosp, Dept Surg, Pittsburgh, PA 15213 USA. [Danielson, Paul D.; Hirsh, Michael P.] Univ Massachusetts, Med Ctr, Dept Pediat Surg, Worcester, MA USA. [Lanning, David A.; Rasmussen, Sara K.] Virginia Commonwealth Univ, Med Ctr, Med Coll Virginia Hosp, Dept Surg, Richmond, VA USA. [Consani, Heitor F. X.] Conjunto Hosp Sorocaba, Div Gen Surg, Sorocaba, SP, Brazil. [Barraco, Robert D.; Pasquale, Michael D.; Hussain, Farheen] Lehigh Valley Hosp, Dept Surg & Trauma, Allentown, PA USA. [Bruch, Steven W.; Drongowski, Robert] Univ Michigan, Pediat Surg Sect, Ann Arbor, MI 48109 USA. [McNeely, P. Daniel] IWK Hlth Ctr, Div Neurosurg, Halifax, NS, Canada. [Fallat, Mary E.; Foley, David S.] Univ Louisville, Dept Surg, Louisville, KY 40292 USA. [Fallat, Mary E.; Foley, David S.] Univ Louisville, Dept Pediat Surg, Louisville, KY 40292 USA. [Iocono, Joseph A.; Bennett, Heather M.] Univ Kentucky, Childrens Hosp, Lexington, KY USA. [Nance, Michael L.] Childrens Hosp Philadelphia, Dept Pediat Surg, Philadelphia, PA 19104 USA. [Waxman, Kenneth; Kam, Kelly] Santa Barbara Cottage Hosp, Dept Surg, Santa Barbara, CA USA. [Scaife, Eric R.; Metzger, Ryan R.] Univ Utah, Dept Pediat Surg, Salt Lake City, UT USA. [Brockmeyer, Douglas L.] Univ Utah, Dept Neurosurg, Salt Lake City, UT USA. Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. RP Masiakos, PT (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, 55 Fruit St,WRN 11, Boston, MA 02114 USA. EM pmasiakos@partners.org OI consani, heitor/0000-0002-1650-8998 NR 47 TC 31 Z9 31 U1 0 U2 7 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 SEP PY 2009 VL 67 IS 3 BP 543 EP 550 DI 10.1097/TA.0b013e3181b57aa1 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 493IL UT WOS:000269729900022 PM 19741398 ER PT J AU Inagami, S Cohen, DA Brown, AF Asch, SM AF Inagami, Sanae Cohen, Deborah A. Brown, Arleen F. Asch, Steven M. TI Body Mass Index, Neighborhood Fast Food and Restaurant Concentration, and Car Ownership SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE Multilevel; Fast food; BMI; Obesity; Mobility; Neighborhood; Restaurant ID HEALTHY FOODS; UNITED-STATES; US ADULTS; INSULIN-RESISTANCE; ALCOHOL OUTLETS; OBESITY; AVAILABILITY; WEIGHT; DISPARITIES; SCHOOLS AB Eating away from home and particularly fast food consumption have been shown to contribute to weight gain. Increased geographic access to fast food outlets and other restaurants may contribute to higher levels of obesity, especially in individuals who rely largely on the local environment for their food purchases. We examined whether fast food and restaurant concentrations are associated with body mass index and whether car ownership might moderate this association. We linked the 2000 US Census data and information on locations of fast food and other restaurants with the Los Angeles Family and Neighborhood Study database, which consists of 2,156 adults sampled from 63 neighborhoods in Los Angeles County. Multilevel modeling was used to estimate associations between body mass index (BMI), fast food and restaurant concentration, and car ownership after adjustment for individual-level factors and socioeconomic characteristics of residential neighborhoods. A high concentration of local restaurants is associated with BMI. Car owners have higher BMIs than non-car owners; however, individuals who do not own cars and reside in areas with a high concentration of fast food outlets have higher BMIs than non-car owners who live in areas with no fast food outlets, approximately 12 lb more (p = 0.02) for an individual with a height of 5 ft. 5 in. Higher restaurant density is associated with higher BMI among local residents. The local fast food environment has a stronger association with BMI for local residents who do not have access to cars. C1 [Inagami, Sanae] VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA USA. [Inagami, Sanae] Univ Pittsburgh, Pittsburgh, PA USA. [Cohen, Deborah A.] RAND Corp, Santa Monica, CA USA. [Brown, Arleen F.; Asch, Steven M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Asch, Steven M.] VA Greater Angeles Healthcare Syst, HSR&D, Los Angeles, CA USA. RP Inagami, S (reprint author), VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA USA. EM sanae.inagami@va.gov; Deborah_Cohen@rand.org; abrown@mednet.ucla.edu; Steven.Asch@va.gov RI Loureiro, Nuno/I-6400-2012 OI Loureiro, Nuno/0000-0002-1166-3219 FU PHS HHS [R40MC00303] NR 44 TC 63 Z9 63 U1 2 U2 23 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD SEP PY 2009 VL 86 IS 5 BP 683 EP 695 DI 10.1007/s11524-009-9379-y PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 486KP UT WOS:000269195200004 PM 19533365 ER PT J AU Dahl, DM Barry, MJ McGovern, FJ Chang, YC Walker-Corkery, E McDougal, WS AF Dahl, Douglas M. Barry, Michael J. McGovern, Francis J. Chang, Yuchaio Walker-Corkery, Elizabeth McDougal, W. Scott TI A Prospective Study of Symptom Distress and Return to Baseline Function After Open Versus Laparoscopic Radical Prostatectomy SO JOURNAL OF UROLOGY LA English DT Article DE prostatectomy; laparoscopy; prostatic neoplasms ID QUALITY-OF-LIFE; CANCER OUTCOMES; COMPLICATIONS; EXPERIENCE AB Purpose: We assessed and compared outcomes following open and laparoscopic radical prostatectomy. Materials and Methods: Patients who were scheduled to undergo open or laparoscopic radical prostatectomy were enrolled in the study and followed prospectively. Before surgery the patients were administered a multi-item validated questionnaire, and were followed by telephone and with mail questionnaires periodically for 12 months. Complications were recorded from chart review and compared. Symptom distress and return to baseline for various parameters were compared between the 2 groups. Results: Of the patients 102 who underwent open prostatectomy and 104 treated with laparoscopic prostatectomy were enrolled in the study. At 1 year 90% in the open and 91% in the laparoscopic group returned the questionnaire. Symptom distress between the 2 groups did not differ at any time during followup. There was no significant difference in return to baseline at 1 year for continence, erectile function or physical function. Of the patients 95% had a return to baseline physical function, approximately 90% do not wear a pad and approximately 50% returned to baseline erectile function with or without phosphodiesterase type 5 inhibitors at 1 year. Although complications were few there was a significant difference in the number for laparoscopic vs open prostatectomy with a slightly higher rate of hematuria and lymphocele formation in the laparoscopic group. Cancer control at 1 year was excellent in both groups. Conclusions: Radical prostatectomy is an effective form of therapy for patients with clinically localized cancer of the prostate. The open and laparoscopic techniques have similar functional outcomes, and these data provide patients a realistic view of what to expect following these 2 methods of radical prostatectomy. C1 [McDougal, W. Scott] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM wmcdougal@partners.org RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU foundation for Informed Medical Decision-Making FX Financial interest and/or other relationship with foundation for Informed Medical Decision-Making. NR 20 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2009 VL 182 IS 3 BP 956 EP 965 DI 10.1016/j.juro.2009.05.044 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 482OT UT WOS:000268899300042 PM 19616252 ER PT J AU Sangwaiya, MJ Marentis, TC Walker, TG Stecker, M Wicky, ST Kalva, SP AF Sangwaiya, Minal Jagtiani Marentis, Theodore C. Walker, T. Gregory Stecker, Michael Wicky, Stephan T. Kalva, Sanjeeva P. TI Safety and Effectiveness of the Celect Inferior Vena Cava Filter: Preliminary Results SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID CLINICAL-EXPERIENCE; PULMONARY-EMBOLISM; FOLLOW-UP; RETRIEVAL; PENETRATION; PROTECTION; TEMPORARY; OUTCOMES AB PURPOSE: To evaluate the safety and effectiveness of the Celect inferior vena cava (IVC) filter during implantation, retrieval, and short-term follow-up. MATERIALS AND METHODS: The clinical data of 73 patients (46 men; age range, 22-89 years) who had a Celect IVC filter implanted between August 2007 and June 2008 were reviewed. Twenty-one (28.8%) presented with pulmonary embolism (PE), 15 (20.54%) with deep vein thrombosis (DVT), 12 (16.4%) with both, and the rest (34.26%) with other symptoms. Indications for filter placement were contraindication to anticoagulation (n = 38; 52%), prophylaxis/added protection (n = 22; 30%), failure of anticoagulation (n = 11; 15%), and complications of anticoagulation (n = 2; 3%). Filters were placed in the infrarenal (n = 71) or suprarenal (n = 2) IVC. Follow-up data were reviewed for filter-related complications and recurrent PE. RESULTS: All filters were successfully deployed. Immediately after fluoroscopy-guided filter deployment in 61 patients, four filters (6.5%) showed significant tilt. During follow-up (mean, 68 days +/- 73), three patients developed symptoms of PE after filter placement; however, computed tomographic (CT) pulmonary angiography demonstrated new PE in only two. Imaging follow-up with radiography (n = 32), CT (n = 11), and/or angiography (n = 4) in 47 patients (at a mean of 62 days +/- 75) showed no filter migration. Follow-up abdominal CT (at a mean of 69 days +/- 58) was available in 18 patients and demonstrated filter-related problems in seven (39%). These included penetration of filter legs in four and fracture/migration of filter components in one. Fourteen filters were successfully retrieved after a median period of 84 days. CONCLUSIONS: The Celect IVC filter can be safely placed but is related to a high incidence of caval filter leg penetration. Symptomatic PE after filter placement confirmed by CT occurred in 2.8% of patients. C1 [Sangwaiya, Minal Jagtiani; Walker, T. Gregory; Wicky, Stephan T.; Kalva, Sanjeeva P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Stecker, Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, GRB 290,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 26 TC 29 Z9 35 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2009 VL 20 IS 9 BP 1188 EP 1192 DI 10.1016/j.jvir.2009.05.033 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 491VT UT WOS:000269610300010 PM 19631561 ER PT J AU Conrad, MF Crawford, RS Kwolek, CJ Brewster, DC Brady, TJ Cambria, RP AF Conrad, Mark F. Crawford, Robert S. Kwolek, Christopher J. Brewster, David C. Brady, Thomas J. Cambria, Richard P. TI Aortic remodeling after endovascular repair of acute complicated type B aortic dissection SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID STENT-GRAFT PLACEMENT; FALSE LUMEN; INTERNATIONAL REGISTRY; EXPERIENCE; MANAGEMENT; ANEURYSMS; INSIGHTS; DISEASE; IRAD AB Objective: The role of thoracic endovascular aortic repair (TEVAR) in the management of acute type B aortic dissection remains undefined. Entry tear coverage during the acute phase is an appealing method to treat acute complications, and by inducing false lumen thrombosis, might also prevent late aneurysm formation. This study evaluated structural changes by serial computed tomography (CT) in the thoracic aorta after TEVAR performed for acute complicated aortic dissection. Methods. Between August 2005 and October 2007, 33 patients with complicated acute type B aortic dissection were treated with TEVAR (19 from a prospective industry sponsored trial, 14 from our institution). CT images obtained preprocedurally (PP), at 1 month (1M), and 1 year (1Y) were evaluated for each patient. Four patients with no postprocedural imaging were excluded. The largest diameters of the thoracic aorta, dissection true lumen, and false lumen were recorded at each time point. Canges in total aortic and true and false lumen diameters were evaluated using a mixed effect analysis of variance model of repeated measures. Results: The average age was 58 years (range, 38-87 years); 26 (81%) were male. Indications for TEVAR included malperfusion syndrome in 17 (53%), refractory hypertension in 14 (44%), impending rupture in 12 (28%), and refractory pain in 14 (44%); 19 (59%) had more than one indication. The average length of aorta covered was 19.5 cm, (range, 10-29.3 cm). The maximum aortic diameter decreased over time (P = .04) and averaged 39.9 (PP), 41.3 (1M), and 34.8 mm (1Y). The true lumen diameter increased over time (P = .02) and averaged 23.7 (PP), 29.0 (1M), and 31.1 mm (1Y). The false lumen diameter decreased (P = .046) and averaged 19.5 (PP), 12.1 (IM), and 9.6 mm (1Y). Partial or complete thrombosis of the false lumen along the stented segment of aorta was recorded in 87% (PP), 93% (IM), and 88% (1Y). Conclusions. TEVAR of acute complicated aortic dissection appears to promote early aortic remodeling. Nearly 90% of patients maintained at least partial false lumen thrombosis at I year. Because continued false lumen patency correlates strongly with late aneurysm formation, such favorable remodeling is considered a surrogate for prevention of late aneurysm, but longer follow-up is required. (J Vase Surg 2009;50:510-7.) C1 [Conrad, Mark F.; Crawford, Robert S.; Kwolek, Christopher J.; Brewster, David C.; Brady, Thomas J.; Cambria, Richard P.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg,Med Sch, Boston, MA 02114 USA. RP Conrad, MF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg,Med Sch, WACC 4,15 Parkman St, Boston, MA 02114 USA. EM mconrad@partners.org NR 38 TC 69 Z9 76 U1 1 U2 4 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 SEP PY 2009 VL 50 IS 3 BP 510 EP 517 DI 10.1016/j.jvs.2009.04.038 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 488KG UT WOS:000269347900006 PM 19497701 ER PT J AU Kassa, A Madani, N Schon, A Haim, H Finzi, A Xiang, SH Wang, LP Princiotto, A Pancera, M Courter, J Smith, AB Freire, E Kwong, PD Sodroski, J AF Kassa, Aemro Madani, Navid Schoen, Arne Haim, Hillel Finzi, Andres Xiang, Shi-Hua Wang, Liping Princiotto, Amy Pancera, Marie Courter, Joel Smith, Amos B., III Freire, Ernesto Kwong, Peter D. Sodroski, Joseph TI Transitions to and from the CD4-Bound Conformation Are Modulated by a Single-Residue Change in the Human Immunodeficiency Virus Type 1 gp120 Inner Domain SO JOURNAL OF VIROLOGY LA English DT Review ID HUMAN MONOCLONAL-ANTIBODY; VIRAL ENVELOPE GLYCOPROTEINS; HUMAN CELL-LINES; SOLUBLE CD4; HIV-1 GP120; CHEMOKINE RECEPTOR; NEUTRALIZATION SENSITIVITY; CYTOPLASMIC DOMAIN; VARIABLE REGIONS; RHESUS-MONKEYS AB Binding to the primary receptor CD4 induces conformational changes in the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein that allow binding to the coreceptor (CCR5 or CXCR4) and ultimately trigger viral membrane-cell membrane fusion mediated by the gp41 transmembrane envelope glycoprotein. Here we report the derivation of an HIV-1 gp120 variant, H66N, that confers envelope glycoprotein resistance to temperature extremes. The H66N change decreases the spontaneous sampling of the CD4-bound conformation by the HIV-1 envelope glycoproteins, thus diminishing CD4-independent infection. The H66N change also stabilizes the HIV-1 envelope glycoprotein complex once the CD4-bound state is achieved, decreasing the probability of CD4-induced inactivation and revealing the enhancing effects of soluble CD4 binding on HIV-1 infection. In the CD4-bound conformation, the highly conserved histidine 66 is located between the receptor-binding and gp41-interactive surfaces of gp120. Thus, a single amino acid change in this strategically positioned gp120 inner domain residue influences the propensity of the HIV-1 envelope glycoproteins to negotiate conformational transitions to and from the CD4-bound state. C1 [Kassa, Aemro; Madani, Navid; Haim, Hillel; Finzi, Andres; Xiang, Shi-Hua; Wang, Liping; Princiotto, Amy; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Dept Pathol,Div AIDS, Boston, MA 02115 USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Pancera, Marie; Kwong, Peter D.] NIAID, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. [Courter, Joel; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Dept Pathol,Div AIDS, Ctr Life Sci Bldg,Room 1009,44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIH [AI24755, AI39420, AI40895]; Center for HIV/AIDS Vaccine Immunology [AI67854]; Center for AIDS Research [AI42848]; Bristol- Myers Squibb Foundation; International AIDS Vaccine Initiative FX This work was supported by NIH grants (AI24755, AI39420, and AI40895), by a Center for HIV/AIDS Vaccine Immunology grant (AI67854), by a Center for AIDS Research grant (AI42848), by an unrestricted research grant from the Bristol- Myers Squibb Foundation, by a gift from the late William F. McCarty- Cooper, and by funds from the International AIDS Vaccine Initiative. NR 103 TC 32 Z9 32 U1 0 U2 12 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 SEP PY 2009 VL 83 IS 17 BP 8364 EP 8378 DI 10.1128/JVI.00594-09 PG 15 WC Virology SC Virology GA 485LF UT WOS:000269122300006 PM 19535453 ER PT J AU Liu, QQ Sun, YT Rihn, S Nolting, A Tsoukas, PN Jost, S Cohen, K Walker, B Alter, G AF Liu, Qingquan Sun, Yongtao Rihn, Suzannah Nolting, Anne Tsoukas, Peter Nicholas Jost, Stephanie Cohen, Kristen Walker, Bruce Alter, Galit TI Matrix Metalloprotease Inhibitors Restore Impaired NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Human Immunodeficiency Virus Type 1 Infection SO JOURNAL OF VIROLOGY LA English DT Article ID NATURAL-KILLER-CELL; HIV-1 INFECTION; CYTOLYTIC FUNCTION; EFFECTOR-CELLS; CUTTING EDGE; HLA-B; RECEPTORS; ACTIVATION; COMPLEMENT; EXPRESSION AB Increasing evidence suggests that NK cells not only are critical in the initial host defense against pathogens but also may contribute to continued protection from human immunodeficiency virus type 1 (HIV-1) disease progression. NK cell cytolysis can be induced directly through diverse receptor families or can be induced indirectly through Fc receptors by antibodies mediating antibody-dependent cellular cytotoxicity (ADCC). ADCC has been implicated in both protection from simian immunodeficiency virus infection and slower progression of HIV-1 disease. ADCC activity declines with advancing infection, and yet the underlying mechanism for this dysfunction has not been defined, nor has it been determined whether the activity can be reconstituted. Here we demonstrate that NK cell-mediated ADCC is severely compromised in chronic HIV infection. The potency of ADCC function was directly correlated with baseline Fc gamma RIIIa receptor (CD16) expression on NK cells. CD16 expression was negatively influenced by elevated expression of a group of enzymes, the matrix metalloproteinases (MMPs), normally involved in tissue/receptor remodeling. Inhibition of MMPs resulted in increased CD16 expression and augmented ADCC activity in response to antibody-coated target cells. These data suggest that MMP inhibitors may improve NK cell-mediated ADCC, which may provide subjects with an opportunity to harness the cytolytic power of NK cells through naturally occurring nonneutralizing HIV-specific antibodies. C1 [Liu, Qingquan; Sun, Yongtao] Fourth Mil Med Univ, Tangdu Hosp, Dept Infect Dis, Xian 710038, Peoples R China. [Liu, Qingquan; Rihn, Suzannah; Nolting, Anne; Tsoukas, Peter Nicholas; Jost, Stephanie; Cohen, Kristen; Walker, Bruce; Alter, Galit] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. [Walker, Bruce] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Sun, YT (reprint author), Fourth Mil Med Univ, Tangdu Hosp, Dept Infect Dis, 1st Xinsi Rd, Xian 710038, Peoples R China. EM yongtaos@hotmail.com; galter@partners.org FU NIH [R01AI080289-01A2] FX This work was supported by NIH grant R01AI080289-01A2. NR 45 TC 49 Z9 50 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2009 VL 83 IS 17 BP 8705 EP 8712 DI 10.1128/JVI.02666-08 PG 8 WC Virology SC Virology GA 485LF UT WOS:000269122300038 PM 19553339 ER PT J AU Robinson, CM Rajaiya, J Walsh, MP Seto, D Dyer, DW Jones, MS Chodosh, J AF Robinson, Christopher M. Rajaiya, Jaya Walsh, Michael P. Seto, Donald Dyer, David W. Jones, Morris S. Chodosh, James TI Computational Analysis of Human Adenovirus Type 22 Provides Evidence for Recombination among Species D Human Adenoviruses in the Penton Base Gene SO JOURNAL OF VIROLOGY LA English DT Article ID ACUTE RESPIRATORY-DISEASE; EPIDEMIC KERATOCONJUNCTIVITIS; BIOINFORMATICS ANALYSIS; CROSSOVER SITES; DNA-SEQUENCE; INFECTION; PROTEIN; REPLICATION; ATTACHMENT; EVOLUTION AB Recombination in human adenoviruses (HAdV) may confer virulence upon an otherwise nonvirulent strain. The genome sequence of species D HAdV type 22 (HAdV-D22) revealed evidence for recombination with HAdV-D19 and HAdV-D37 within the capsid penton base gene. Bootscan analysis demonstrated that recombination sites within the penton base gene frame the coding sequences for the two external hypervariable loops in the protein. A similar pattern of recombination was evident within other HAdV-D types but not other HAdV species. Further study of recombination among HAdVs is needed to better predict possible recombination events among wild-type viruses and adenoviral gene therapy vectors. C1 [Robinson, Christopher M.; Rajaiya, Jaya; Chodosh, James] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Howe Lab, Boston, MA 02114 USA. [Walsh, Michael P.; Seto, Donald] George Mason Univ, Dept Bioinformat & Computat Biol, Manassas, VA USA. [Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA. [Jones, Morris S.] David Grant USAF Med Ctr, Clin Investigat Facil, Travis, CA USA. RP Chodosh, J (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Howe Lab, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu FU NEI NIH HHS [R01 EY013124] NR 44 TC 32 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2009 VL 83 IS 17 BP 8980 EP 8985 DI 10.1128/JVI.00786-09 PG 6 WC Virology SC Virology GA 485LF UT WOS:000269122300066 PM 19553309 ER PT J AU Norton, MC Piercy, KW Rabins, PV Green, RC Breitner, JCS Ostbye, T Corcoran, C Welsh-Bohmer, KA Lyketsos, CG Tschanz, JT AF Norton, Maria C. Piercy, Kathleen W. Rabins, Peter V. Green, Robert C. Breitner, John C. S. Ostbye, Truls Corcoran, Christopher Welsh-Bohmer, Kathleen A. Lyketsos, Constantine G. Tschanz, JoAnn T. TI Caregiver-Recipient Closeness and Symptom Progression in Alzheimer Disease. The Cache County Dementia Progression Study SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 14-17, 2008 CL Orlando, FL SP Amer Assoc Geriat Psychiat DE Alzheimer's disease; Caregiving; Interpersonal relations ID PROGNOSTIC-FACTORS; FAMILY CAREGIVERS; BEHAVIOR; DECLINE; IMPACT; CARE; HOME; INTERVENTION; QUALITY; AD AB Applying Rusbult's investment model of dyadic relationships, we examined the effect of caregiver-care recipient relationship closeness (RC) on cognitive and functional decline in Alzheimer's disease. After diagnosis, 167 participants completed up to six visits, observed over an average of 20 months. Participants were 64% women, had a mean age of 86 years, and mean dementia duration of 4 years. Caregiver-rated closeness was measured using a six-item scale. In mixed models adjusted for dementia severity, dyads with higher levels of closeness (p <.05) and with spouse caregivers (p =.01) had slower cognitive decline. Effect of higher RC on functional decline was greater with spouse caregivers (p =.007). These findings of attenuated Alzheimer's dementia (AD) decline with closer relationships, particularly with spouse caregivers, are consistent with investment theory. Future interventions designed to enhance the caregiving dyadic relationship may help slow decline in AD. C1 [Norton, Maria C.; Piercy, Kathleen W.] Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. [Norton, Maria C.; Tschanz, JoAnn T.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Norton, Maria C.; Piercy, Kathleen W.; Corcoran, Christopher; Tschanz, JoAnn T.] Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. [Rabins, Peter V.; Lyketsos, Constantine G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 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. [Green, Robert C.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Breitner, John C. S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Breitner, John C. S.] Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98195 USA. [Ostbye, Truls] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Corcoran, Christopher] Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Med Ctr, Bryan Alzheimers Dis Res Ctr, Durham, NC USA. RP Norton, MC (reprint author), Utah State Univ, Dept Family Consumer & Human Dev, 2905 Old Main Hill, Logan, UT 84322 USA. EM maria.norton@usu.edu RI Corcoran, Chris/F-2155-2010; piercy, kathleen/F-4808-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013 FU NIA NIH HHS [R01 AG021136-01, AG011380, AG018712, AG021136, AG027841, AG031272, R01 AG021136, R01 AG021136-02, R01 AG021136-03, R01 AG021136-04, R01 AG021136-05, R01 AG021136-06A2] NR 47 TC 38 Z9 38 U1 3 U2 12 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD SEP PY 2009 VL 64 IS 5 BP 560 EP 568 DI 10.1093/geronb/gbp052 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 489RX UT WOS:000269441100003 PM 19564210 ER PT J AU Betancourt, JR Cervantes, MC AF Betancourt, Joseph R. Cervantes, Marina C. TI CROSS-CULTURAL MEDICAL EDUCATION IN THE UNITED STATES: KEY PRINCIPLES AND EXPERIENCES SO KAOHSIUNG JOURNAL OF MEDICAL SCIENCES LA English DT Review DE cross-cultural care; cross-cultural medical education; patient-based approach ID CARE; STUDENTS; HEALTH; COMPETENCE; LESSONS AB The field of cross-cultural care focuses on the ability to communicate effectively and provide quality health care to patients from diverse sociocultural backgrounds. In recent years, medical schools in the United States have increasingly recognized the growing importance of incorporating cross-cultural curricula into medical education. Cross-cultural medical education in the United States has emerged for four reasons: (1) the need for providers to have the skills to care for a diverse patient population; (2) the link between effective communication and health Outcomes; (3) the presence of racial/ethnic disparities that are, in part, due to poor communication across cultures; and (4) medical school accreditation requirements. There are three major approaches to cross-cultural education: (1) the cultural sensitivity/awareness approach that focuses on attitudes; (2) the multi-cultural/categorical approach that focuses on knowledge; and (3) the cross-cultural approach that focuses on skills. The patient-based approach to cross-cultural care combines these three concepts into a framework that can be used to care for any patient, anytime, anywhere. Ultimately, if cross-cultural medical education is to evolve, students must believe it is important and understand that the categorical approach can lead to stereotyping; it should be taught using patient cases and highlighting clinical applications; it should be embedded in a longitudinal, developmentally appropriate fashion; and it should be integrated into the larger curriculum whenever possible. At the Harvard Medical School, we have tried to apply all of these lessons to our work, and we have started to develop a strategic integration process where we try to raise awareness, impart knowledge, and teach cross-cultural skills over the 4 years of schooling. C1 [Betancourt, Joseph R.; Cervantes, Marina C.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Betancourt, Joseph R.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Betancourt, Joseph R.] Massachusetts Gen Hosp, Multicultural Educ & Multicultural Affairs Off, Boston, MA 02114 USA. [Betancourt, Joseph R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Betancourt, JR (reprint author), 50 Staniford St,Suite 942, Boston, MA 02114 USA. EM jbetancourt@partners.org NR 22 TC 15 Z9 16 U1 2 U2 5 PU KAOHSIUNG JOURNAL MEDICAL SCIENCES PI KAOHSIUNG CITY PA KAOHSIUNG MEDICAL COLL, NO 100, SHIH-CHUAN 1ST RD, KAOHSIUNG CITY, 00000, TAIWAN SN 1607-551X J9 KAOHSIUNG J MED SCI JI Kaohsiung J. Med. Sci. PD SEP PY 2009 VL 25 IS 9 BP 471 EP 478 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 505NB UT WOS:000270699400002 PM 19717365 ER PT J AU Lum, G D'Amarino, MJ AF Lum, Gifford D'Amarino, Michael J. TI Use of Laboratory Robots for Transport and Delivery of Blood Products SO LABMEDICINE LA English DT Article C1 [Lum, Gifford; D'Amarino, Michael J.] VA Boston Healthcare Syst, Boston, MA USA. RP Lum, G (reprint author), VA Boston Healthcare Syst, Boston, MA USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD SEP PY 2009 VL 40 IS 9 BP 517 EP 522 DI 10.1309/LMR9EV8GT9XCQAMK PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 486DM UT WOS:000269175900001 ER PT J AU Takeda, M Briggs, LE Wakimoto, H Marks, MH Warren, SA Lu, JT Weinberg, EO Robertson, KD Chien, KR Kasahara, H AF Takeda, Morihiko Briggs, Laura E. Wakimoto, Hiroko Marks, Melissa H. Warren, Sonisha A. Lu, Jonathan T. Weinberg, Ellen O. Robertson, Keith D. Chien, Kenneth R. Kasahara, Hideko TI Slow progressive conduction and contraction defects in loss of Nkx2-5 mice after cardiomyocyte terminal differentiation SO LABORATORY INVESTIGATION LA English DT Article DE Nkx2-5; cardiomyocyte; conduction defects; gene targeting; hypertrophy ID CONGENITAL HEART-DISEASE; HOMEOBOX GENE NKX2-5; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; TRANSCRIPTION FACTORS; UP-REGULATION; ADULT HEART; MUTATIONS; HYPERTROPHY; CSX/NKX2.5 AB Mutations in homeoprotein NKX2-5 are linked to human congenital heart disease, resulting in various cardiac anomalies, as well as in postnatal progressive conduction defects and occasional left ventricular dysfunction; yet the function of Nkx2-5 in the postnatal period is largely unexplored. In the heart, the majority of cardiomyocytes are believed to complete cell-cycle withdrawal shortly after birth, which is generally accompanied by a re-organization of chromatin structure shown in other tissues. We reasoned that the effects of the loss of Nkx2-5 in mice may be different after cell-cycle withdrawal compared with those of the perinatal loss of Nkx2-5, which results in rapid conduction and contraction defects within 4 days after the deletion of Nkx2-5 alleles (Circ Res. 2008; 103: 580). In this study, floxed-Nkx2-5 alleles were deleted using tamoxifen-inducible Cre transgene (Cre-ER) beginning at 2 weeks of age. The loss of Nkx2-5 beginning at 2 weeks of age resulted in conduction and contraction defects similar to the perinatal loss of Nkx2-5, however, with a substantially slower disease progression shown by 11 atrioventricular block at 6 weeks of age (4 weeks after tamoxifen injections) and heart enlargement after 12 weeks of age (10 weeks after tamoxifen injections). The phenotypes were accompanied by a slower and smaller degree of reduction of several critical Nkx2-5 downstream targets that were observed in mice with a perinatal loss of Nkx2-5. These results suggest that Nkx2-5 is necessary for proper conduction and contraction after 2 weeks of age, but with a substantially distinct level of necessity at 2 weeks of age compared with that in the perinatal period. Laboratory Investigation (2009) 89, 983-993; doi:10.1038/labinvest.2009.59; published online 22 June 2009 C1 [Takeda, Morihiko; Briggs, Laura E.; Marks, Melissa H.; Warren, Sonisha A.; Kasahara, Hideko] Univ Florida, Coll Med, Dept Physiol & Funct Genom, Gainesville, FL 32610 USA. [Wakimoto, Hiroko] Tokyo Med & Dent Sch, Dept Pediat, Tokyo, Japan. [Lu, Jonathan T.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. [Weinberg, Ellen O.] Boston Univ, Med Ctr, Boston, MA USA. [Robertson, Keith D.] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. [Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Kasahara, H (reprint author), Univ Florida, Coll Med, Dept Physiol & Funct Genom, POB 100274,1600 SW Archer Rd,M540, Gainesville, FL 32610 USA. EM hkasahar@phys.med.ufl.edu FU National Institutes of Health [HL081577]; American Heart Association-National SDG [0035258N] FX We greatly appreciate E Chan and P Sayeski for their valuable suggestions and technical support. This study was supported by the National Institutes of Health (HL081577 to HK) and the American Heart Association-National SDG grant (0035258N to HK). NR 35 TC 27 Z9 27 U1 0 U2 1 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 SEP PY 2009 VL 89 IS 9 BP 983 EP 993 DI 10.1038/labinvest.2009.59 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 488BI UT WOS:000269323600003 PM 19546853 ER PT J AU Jarvik, JG Comstock, BA Kliot, M Turner, JA Chan, L Heagerty, PJ Hollingworth, W Kerrigan, CL Deyo, RA AF Jarvik, Jeffrey G. Comstock, Bryan A. Kliot, Michel Turner, Judith A. Chan, Leighton Heagerty, Patrick J. Hollingworth, William Kerrigan, Carolyn L. Deyo, Richard A. TI Surgery versus non-surgical therapy for carpal tunnel syndrome: a randomised parallel-group trial SO LANCET LA English DT Article ID WORKERS COMPENSATION; STEROID INJECTION; CLINICAL-TRIAL; HEALTH; RESPONSIVENESS; QUESTIONNAIRE; POPULATION; ULTRASOUND; SYMPTOMS AB Background A previous randomised controlled trial reported greater efficacy of surgery than of splinting for patients with carpal tunnel syndrome. Our aim was to compare surgical versus multi-modality, non-surgical treatment for patients with carpal tunnel syndrome without denervation. We hypothesised that surgery would result in improved functional and symptom outcomes. Methods In this parallel-group randomised controlled trial, we randomly assigned 116 patients from eight academic and private practice centres, using computer-generated random allocation stratified by site, to carpal tunnel surgery (n=57) or to a well-defined, non-surgical treatment (including hand therapy and ultrasound; n=59). The primary outcome was hand function measured by the Carpal Tunnel Syndrome Assessment Questionnaire (CTSAQ) at 12 months assessed by research personnel unaware of group assignment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00032227. Findings 44 (77%) patients assigned to surgery underwent surgery. At 12 months, 101 (87%) completed follow-up and were analysed (49 of 57 assigned to surgery and 52 of 59 assigned to non-surgical treatment). Analyses showed a significant 12-month adjusted advantage for surgery in function (CTSAQ function score: Delta -0.40, 95% CI 0.11-0.70, p=0.0081) and symptoms (CTSAQ symptom score: 0.34, 0.02-0.65, p=0.0357). There were no clinically important adverse events and no surgical complications. Interpretation Symptoms in both groups improved, but surgical treatment led to better outcome than did non-surgical treatment. However, the clinical relevance of this difference was modest. Overall, our study confirms that surgery is useful for patients with carpal tunnel syndrome without denervation. Funding NIH/NIAMS 5P60AR048093 and the Intramural Research Program of the NIH Clinical Center. C1 [Jarvik, Jeffrey G.] Univ Washington, Dept Radiol, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA. [Jarvik, Jeffrey G.; Kliot, Michel] Univ Washington, Dept Neurol Surg, Sch Med, Seattle, WA 98104 USA. [Turner, Judith A.] Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98104 USA. [Jarvik, Jeffrey G.] Univ Washington, Dept Hlth Serv, Sch Publ Hlth, Seattle, WA 98104 USA. [Comstock, Bryan A.; Heagerty, Patrick J.] Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98104 USA. [Jarvik, Jeffrey G.; Comstock, Bryan A.; Turner, Judith A.; Heagerty, Patrick J.] Univ Washington, Comparat Effectiveness Cost & Outcomes Res Ctr, Seattle, WA 98104 USA. [Kliot, Michel] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Chan, Leighton] NIH, Intramural Res Program, Ctr Clin, Bethesda, MD 20892 USA. [Kerrigan, Carolyn L.] Dartmouth Hitchcock Med Ctr, Sect Plast Surg, Lebanon, NH 03766 USA. [Hollingworth, William] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. RP Jarvik, JG (reprint author), Univ Washington, Dept Radiol, Harborview Med Ctr, Sch Med, Box 359728,325 Ninth Ave, Seattle, WA 98104 USA. EM jarviks@comcast.net FU NIH/NIAMS [SP60AR048093]; Intramural Research Program of the NIH FX NIH/NIAMS SP60AR048093 and the Intramural Research Program of the NIH Clinical Center. NR 31 TC 31 Z9 33 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD SEP-OCT PY 2009 VL 374 IS 9695 BP 1074 EP 1081 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 501HA UT WOS:000270370900029 ER PT J AU Weiser, TG Makary, MA Haynes, AB Dziekan, G Berry, WR Gawande, AA AF Weiser, Thomas G. Makary, Martin A. Haynes, Alex B. Dziekan, Gerald Berry, William R. Gawande, Atul A. CA Safe Surg Saves Lives Measurement Safe Surg Saves Lives Study Grp TI Standardised metrics for global surgical surveillance SO LANCET LA English DT Article ID CARE AB Public health surveillance relies on standardised metrics to evaluate disease burden and health system performance. Such metrics have not been developed for surgical services despite increasing volume, substantial cost, and high rates of death and disability associated with surgery. The Safe Surgery Saves Lives initiative of WHO's Patient Safety Programme has developed standardised public health metrics for surgical care that are applicable worldwide. We assembled an international panel of experts to develop and define metrics for measuring the magnitude and effect of surgical care in a population, while taking into account economic feasibility and practicability. This panel recommended six measures for assessing surgical services at a national level: number of operating rooms, number of operations, number of accredited surgeons, number of accredited anaesthesia professionals, day-of-surgery death ratio, and postoperative in-hospital death ratio. We assessed the feasibility of gathering such statistics at eight diverse hospitals in eight countries and incorporated them into the WHO Guidelines for Safe Surgery, in which methods for data collection, analysis, and reporting are outlined. C1 [Weiser, Thomas G.; Haynes, Alex B.; Berry, William R.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Weiser, Thomas G.; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Makary, Martin A.] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. [Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Dziekan, Gerald] WHO Patient Safety Programme, Geneva, Switzerland. RP Gawande, AA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Kresge 400,677 Huntington Ave, Boston, MA 02115 USA. EM safesurgery@hsph.harvard.edu OI Merry, Alan/0000-0001-7100-009X FU WHO FX This work was supported by WHO, which also provided funding for AAG as lead of the Safe Surgery Saves Lives Initiative. WHO had no role in the decision to submit this work for publication. We would like to thank the following people for help in supplying data: Vanessa Beavis, Kylie Edwards, Ian Civil (Auckland, New Zealand); Amit Vats (London, UK); Chandra Meghrajani (Manila, Philippines); Vickie Kolios-Morris (Seattle, USA); Robert Bell, Joe Slack (Toronto, Canada). NR 15 TC 32 Z9 32 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD SEP-OCT PY 2009 VL 374 IS 9695 BP 1113 EP 1117 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 501HA UT WOS:000270370900034 ER PT J AU Tabrizi, SJ Langbehn, DR Leavitt, BR Roos, RAC Durr, A Craufurd, D Kennard, C Hicks, SL Fox, NC Scahill, RI Borowsky, B Tobin, AJ Rosas, HD Johnson, H Reilmann, R Landwehrmeyer, B Stout, JC AF Tabrizi, Sarah J. Langbehn, Douglas R. Leavitt, Blair R. Roos, Raymund A. C. Durr, Alexandra Craufurd, David Kennard, Christopher Hicks, Stephen L. Fox, Nick C. Scahill, Rachael I. Borowsky, Beth Tobin, Allan J. Rosas, H. Diana Johnson, Hans Reilmann, Ralf Landwehrmeyer, Bernhard Stout, Julie C. CA TRACK-HD Investigators TI Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data SO LANCET NEUROLOGY LA English DT Article ID AGE-OF-ONSET; TRINUCLEOTIDE REPEAT; PREDICT-HD; DYSFUNCTION; CARRIERS; GENE; NEUROPATHOLOGY; RECOGNITION; DIAGNOSIS; SYMPTOMS AB Background Huntington's disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects adults in mid-life. Our aim was to identify sensitive and reliable biomarkers in premanifest carriers of mutated HTT and in individuals with early HD that could provide essential methodology for the assessment of therapeutic interventions. Methods This multicentre study uses an extensive battery of novel assessments, including multi-site 3T MRI, clinical cognitive, quantitative motor, oculomotor, and neuropsychiatric measures. Blinded analyses were done on the baseline cross-sectional data from 366 individuals: 123 controls, 120 premanifest (pre-HD) individuals, and 123 patients with early HD. Findings The first participant was enrolled in January, 2008, and all assessments were completed by August, 2008. Cross-sectional analyses identified significant changes in whole-brain volume, regional grey and white matter differences, impairment in a range of voluntary neurophysiological motor, and oculomotor tasks, and cognitive and neuropsychiatric dysfunction in premanifest HD gene carriers with normal motor scores through to early clinical stage 2 disease. Interpretation We show the feasibility of rapid data acquisition and the use of multi-site 3T MRI and neurophysiological motor measures in a large multicentre study. Our results provide evidence for quantifiable biological and clinical alterations in HTT expansion carriers compared with age-matched controls. Many parameters differ from age-matched controls in a graded fashion and show changes of increasing magnitude across our cohort, who range from about 16 years from predicted disease diagnosis to early HD. These findings might help to define novel quantifiable endpoints and methods for rapid and reliable data acquisition, which could aid the design of therapeutic trials. Funding CHDI/High Q Foundation. C1 [Tabrizi, Sarah J.; TRACK-HD Investigators] UCL, Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England. [Langbehn, Douglas R.; Johnson, Hans] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Langbehn, Douglas R.] Univ Iowa, Dept Biostat, Iowa City, IA USA. [Leavitt, Blair R.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Roos, Raymund A. C.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. [Durr, Alexandra] Hop La Pitie Salpetriere, APHP, Dept Genet & Cytogenet, Paris, France. [Durr, Alexandra] Hop La Pitie Salpetriere, APHP, INSERM, UMR 5679, Paris, France. [Craufurd, David] St Marys Hosp, Med Genet Res Grp, Manchester M13 0JH, Lancs, England. [Kennard, Christopher; Hicks, Stephen L.] Univ Oxford, Dept Clin Neurol, Oxford, England. [Borowsky, Beth; Tobin, Allan J.] CHDI Fdn, CHDI Management, New York, NY USA. [Rosas, H. Diana] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Reilmann, Ralf] Univ Munster, Dept Neurol, D-4400 Munster, Germany. [Landwehrmeyer, Bernhard] Univ Ulm, Dept Neurol, D-7900 Ulm, Germany. [Stout, Julie C.] Monash Univ, Sch Psychol Psychiat & Psychol Med, Clayton, Vic 3800, Australia. [Stout, Julie C.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. RP Tabrizi, SJ (reprint author), UCL, Inst Neurol, Dept Neurodegenerat Dis, Box 104,Queen Sq, London WC1N 3BG, England. EM sarah.tabrizi@prion.uci.ac.uk RI Ordidge, Roger/F-2755-2010; Leavitt, Blair/G-1934-2012; Craufurd, David/G-5277-2013; Fox, Nick/B-1319-2009; OI Fox, Nick/0000-0002-6660-657X; Tabrizi, Sarah/0000-0003-2716-2045; Wild, Edward/0000-0002-6921-7887; Johnson, Hans/0000-0001-9513-2660; Ordidge, Roger/0000-0002-1005-3654; Landwehrmeyer, Georg Bernhard/0000-0003-3375-790X FU Department of Health NIHR Biomedical Research Centres FX The authors wish to thank the TRACK-H D study participants, the CHDI/High Q Foundation, a not-for-profit organisation dedicated to finding treatments for HD, Sherry Lifer, Saiqah Munir, Azra Hassanali, Daniel van Kammen, Ethan Signer, Michael Hayden, Susan Creighton, 2mt Software GmbH, Anne Rosser, Andrea Nemeth, Emma Hobson, the Huntingtorfs disease clinic at Guy's hospital, Centre d'investigafion Clinique Hospital de la Salpftriere Paris, National Hospital for Neurology London, Leiden University Medical Centre, Katja Vitkin, Felix Mudoh Tita, Irina, Vainer, Theresia Kelm, Biorep Technologies, Arthur Toga, Laboratory of Neurc, Imaging UCLA (LONI) and IXICO for all their help in enabling all aspects of TRACK-HD to move forward, and also to Ray Young for graphics and the PREDICPHD investigators for helpful advice. Some of this work was undertaken at University College London Hospital/ University College London, which received funding from the Department of Health NIHR Biomedical Research Centres funding scheme. NR 40 TC 330 Z9 333 U1 4 U2 28 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 SEP PY 2009 VL 8 IS 9 BP 791 EP 801 DI 10.1016/S1474-4422(09)70170-X PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 487AD UT WOS:000269241700007 PM 19646924 ER PT J AU Austin, DF Konrad-Martin, D Griest, S McMillan, GP McDermott, D Fausti, S AF Austin, Donald F. Konrad-Martin, Dawn Griest, Susan McMillan, Garnett P. McDermott, Daniel Fausti, Stephen TI Diabetes-Related Changes in Hearing SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Combined Sections Meeting of the Southern/Middle Triological-Society CY JAN 08-11, 2009 CL Bonita Springs, FL SP Triol Soc DE Audiologic monitoring; hearing loss; Veterans ID IMPAIRMENT; MELLITUS AB Objectives/Hypothesis: Determine the effects on hearing of diabetes mellitus (DM) severity. Study Design: We conducted a cross-sectional study among Veterans to investigate the relationship of diabetes severity and hearing in randomly selected subjects with (165) and without (137) DM and who had no more than a moderate hearing loss. Methods: Subjects were classified by three age tertiles (<50, 50-56, and 57+ years). Diabetes severity was classified as insulin-dependent (IDDM), non-insulin-dependent (NIDDM), or no DM. Other DM measures included concurrent serum glucose, serum HbA(1c), duration of disease, and several measures of DM-related complications. Pure-tone thresholds were measured in both ears of each subject at frequencies from 250 Hz through 14,000 Hz. Outcome measures were adjusted for age and frequency and analyzed for differences between subject groups using analysis of variance. Contrasts of the mean NIDDM and IDDM thresholds at each frequency to the DM group, and controlled for the effects of frequency, age, and interactions were modeled. Results: There was greater hearing loss in younger tertile DM subjects compared to those without DM. Significant hearing differences were at all frequencies for NIDDM subjects, but for IDDM subjects, differences were at 1,000 Hz and below, and 10,000 Hz and above. Over age 50 years, there were significant associations between hearing at low frequencies and IDDM only. Self-report of prior noise exposure did not explain observed differences. Conclusions: Diabetes is associated with an increased risk of hearing loss, and this difference is manifest particularly in adults <50 years old. C1 [Austin, Donald F.; Konrad-Martin, Dawn; Griest, Susan; McMillan, Garnett P.; McDermott, Daniel; Fausti, Stephen] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, VA Rehabil Res & Dev Serv, Portland, OR 97239 USA. [Austin, Donald F.] Oregon Hlth & Sci Univ, Sch Med, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Konrad-Martin, Dawn; Griest, Susan; Fausti, Stephen] Oregon Hlth & Sci Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. RP Konrad-Martin, D (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, VA Rehabil Res & Dev Serv, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM dawn.martin@va.gov NR 12 TC 29 Z9 37 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2009 VL 119 IS 9 BP 1788 EP 1796 DI 10.1002/lary.20570 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 491JB UT WOS:000269573600019 PM 19593813 ER PT J AU Heinrichs, S Kulkarni, RV Bueso-Ramos, CE Levine, RL Loh, ML Li, C Neuberg, D Kornblau, SM Issa, JP Gilliland, DG Garcia-Manero, G Kantarjian, HM Estey, EH Look, AT AF Heinrichs, S. Kulkarni, R. V. Bueso-Ramos, C. E. Levine, R. L. Loh, M. L. Li, C. Neuberg, D. Kornblau, S. M. Issa, J-P Gilliland, D. G. Garcia-Manero, G. Kantarjian, H. M. Estey, E. H. Look, A. T. TI Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics SO LEUKEMIA LA English DT Article DE myelodysplastic syndrome; SNP array; uniparental disomy ID COMMONLY DELETED REGION; HUMAN GENOME; CHROMOSOMAL LESIONS; STRUCTURAL VARIANTS; MYELOID-LEUKEMIA; COPY NUMBER; GENE; POLYMORPHISM; DISEASES; CANCER AB Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40 -60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities. Leukemia (2009) 23, 1605 -1613; doi:10.1038/leu.2009.82; published online 23 April 2009 C1 [Heinrichs, S.; Kulkarni, R. V.; Look, A. T.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Bueso-Ramos, C. E.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Levine, R. L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Loh, M. L.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Li, C.; Neuberg, D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kornblau, S. M.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat Cellular Therapy, Houston, TX 77030 USA. [Issa, J-P; Garcia-Manero, G.; Kantarjian, H. M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Gilliland, D. G.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Estey, E. H.] Univ Washington, Div Hematol, Med Ctr, Seattle, WA 98195 USA. [Estey, E. H.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Mayer Bldg,Rm 630, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu FU NIH [P01 CA-108631] FX We thank Martin H Nguyen and Michael Fernandez (MDACC) as well as Nikki Flores and Elena Wang (USCF) for excellent technical assistance and we are grateful to John Gilbert for editorial review and helpful discussions. We also thank Lorna Mangus for administrative support. The work was supported in part by NIH P01 Grant CA-108631 from the National Institutes of Health. NR 34 TC 54 Z9 56 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 2009 VL 23 IS 9 BP 1605 EP 1613 DI 10.1038/leu.2009.82 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 492QN UT WOS:000269674200009 PM 19387468 ER PT J AU Perrone, G Hideshima, T Ikeda, H Okawa, Y Calabrese, E Gorgun, G Santo, L Cirstea, D Raje, N Chauhan, D Baccarani, M Cavo, M Anderson, KC AF Perrone, G. Hideshima, T. Ikeda, H. Okawa, Y. Calabrese, E. Gorgun, G. Santo, L. Cirstea, D. Raje, N. Chauhan, D. Baccarani, M. Cavo, M. Anderson, K. C. TI Ascorbic acid inhibits antitumor activity of bortezomib in vivo SO LEUKEMIA LA English DT Article DE multiple myeloma; ascorbic acid; antioxidant; bortezomib ID MULTIPLE-MYELOMA CELLS; VITAMIN-C PHARMACOKINETICS; PROTEASOME INHIBITION; CARCINOMA-CELLS; ANTIOXIDANTS; COMBINATION; THERAPY; CANCER; VITRO; DEXAMETHASONE AB Earlier studies have shown that ascorbic acid (vitamin C) inhibits bortezomib-induced cytotoxicity against cancer cells in vitro. However, the clinical significance of vitamin C on bortezomib treatment is unclear. In this study, we examined whether daily oral intake of vitamin C inhibits antimultiple myeloma (MM) activities of bortezomib. Vitamin C, at orally achievable concentrations, inhibited in vitro MM cell cytotoxicity of bortezomib and blocked its inhibitory effect on 20S proteasome activity. Specifically, plasma collected from healthy volunteers taking 1 g/day vitamin C reduced bortezomib-induced MM cell death in vitro. This antagonistic effect of vitamin C against proteasome inhibitors is limited to the boronate class of inhibitors (bortezomib and MG262). In vivo activity of this combination treatment was then evaluated using our xenograft model of human MM in SCID (severe combined immune-deficient) mice. Bortezomib (0.1 mg/kg twice a week for 4 weeks) significantly inhibits in vivo MM cell growth, which was blocked by oral vitamin C (40 mg/kg/day). Therefore, our results for the first time show that vitamin C can significantly reduce the activity of bortezomib treatment in vivo; and importantly, suggest that patients receiving treatment with bortezomib should avoid taking vitamin C dietary supplements. Leukemia (2009) 23, 1679 -1686; doi:10.1038/leu.2009.83; published online 16 April 2009 C1 [Perrone, G.; Hideshima, T.; Ikeda, H.; Okawa, Y.; Calabrese, E.; Gorgun, G.; Santo, L.; Cirstea, D.; Raje, N.; Chauhan, D.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Perrone, G.; Hideshima, T.; Ikeda, H.; Okawa, Y.; Calabrese, E.; Gorgun, G.; Santo, L.; Cirstea, D.; Raje, N.; Chauhan, D.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA. [Perrone, G.; Baccarani, M.; Cavo, M.] Univ Bologna, Sch Med, Dept Hematol, Seragnoli Inst Hematol & Med Oncol, Bologna, Italy. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,LeBow Inst Myeloma Therapeut, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu OI CAVO, MICHELE/0000-0003-4514-3227 NR 37 TC 40 Z9 41 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 2009 VL 23 IS 9 BP 1679 EP 1686 DI 10.1038/leu.2009.83 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 492QN UT WOS:000269674200018 PM 19369963 ER PT J AU Gray, RJ AF Gray, Robert J. TI Weighted analyses for cohort sampling designs (vol 15, pg 24, 2009) SO LIFETIME DATA ANALYSIS LA English DT Correction C1 Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Gray, RJ (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM gray@jimmy.harvard.edu NR 2 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD SEP PY 2009 VL 15 IS 3 BP 411 EP 411 DI 10.1007/s10985-009-9116-6 PG 1 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 461TY UT WOS:000267296000008 ER PT J AU Wiggins, GC Polimeni, JR Potthast, A Schmitt, M Alagappan, V Wald, LL AF Wiggins, Graham C. Polimeni, Jonathan R. Potthast, Andreas Schmitt, Melanie Alagappan, Vijay Wald, Lawrence L. TI 96-Channel Receive-Only Head Coil for 3 Tesla: Design Optimization and Evaluation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE phased array; 96-channel; RF coil design; SNR; g-factor ID TO-NOISE RATIO; CARDIAC COIL; ARRAY; MRI; SYSTEM AB The benefits and challenges of highly parallel array coils for head imaging were investigated through the development of a 3T receive-only phased-array head coil with 96 receive elements constructed on a close-fitting helmet-shaped former. We evaluated several designs for the coil elements and matching circuitry, with particular attention to sources of signal-to-noise ratio (SNR) loss, including various sources of coil loading and coupling between the array elements. The SNR and noise amplification (g-factor) in accelerated imaging were quantitatively evaluated in phantom and human imaging and compared to a 32-channel array built on an identical helmet-shaped former and to a larger commercial 12-channel head coil. The 96-channel coil provided substantial SNR gains in the distal cortex compared to the 12- and 32-channel coils. The central SNR for the 96-channel coil was similar to the 32-channel coil for optimum SNR combination and 20% lower for root-sum-of-squares combination. There was a significant reduction in the maximum g-factor for 96 channels compared to 32; for example, the 96-channel maximum g-factor was 65% of the 32-channel value for acceleration rate 4. The performance of the array is demonstrated in highly accelerated brain images. Magn Reson Med 62:754-762, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Wiggins, Graham C.; Polimeni, Jonathan R.; Schmitt, Melanie; Alagappan, Vijay; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Potthast, Andreas] Siemens Healthcare, Erlangen, Germany. [Wald, Lawrence L.] Harvard MIT Div Hlth Sci Technol, Cambridge, MA USA. RP Wiggins, GC (reprint author), AA Martinos Ctr Biomed Imaging, Bldg 149 13th St,Mailcode 149-2301, Charlestown, MA 02129 USA. EM gwiggins@nmr.mgh.harvard.edu RI Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; FU National Institutes of Health [P41RR014075, R01EB006847, R01EB000790]; Institute for Mental Illness and Neuroscience Discovery (MIND) FX Grant Sponsor: National Institutes of Health; Grant numbers: P41RR014075, R01EB006847, R01EB000790; Grant sponsor: Institute for Mental Illness and Neuroscience Discovery (MIND). NR 34 TC 106 Z9 109 U1 2 U2 14 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD SEP PY 2009 VL 62 IS 3 BP 754 EP 762 DI 10.1002/mrm.22028 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 489FG UT WOS:000269404900023 PM 19623621 ER PT J AU Simon, K Mukundan, A Dewundara, S Van Remmen, H Dombkowski, AA Cabelof, DC AF Simon, Kirk Mukundan, Anju Dewundara, Samantha Van Remmen, Holly Dombkowski, Alan A. Cabelof, Diane C. TI Transcriptional profiling of the age-related response to genotoxic stress points to differential DNA damage response with age SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE DNA repair; p53; Aging; DNA damage response; Cell cycle ID BASE EXCISION-REPAIR; DOUBLE-STRAND BREAKS; OXIDATIVE STRESS; IN-VIVO; SENESCENT CELLS; S-PHASE; CHECKPOINT; INDUCTION; EXPOSURE; MICE AB The p53 DNA damage response attenuated with age and we have evaluated downstream factors in the DNA damage response. In old animals p21 protein accumulates in the whole cell fraction but significantly declines in the nucleus, which may after cell cycle and apoptotic programs in response to DNA damage. We evaluated the transcriptional response to DNA damage in young and old and find 2692 genes are differentially regulated in old compared to young in response to oxidative stress (p < 0.005). As anticipated, the transcriptional profile of young mice is consistent with DNA damage induced cell cycle arrest while the profile of old mice is consistent with cell cycle progression in the presence of DNA damage, suggesting the potential for catastrophic accumulation of DNA damage at the replication fork. Unique sets of DNA repair genes are induced in response to damage in old and young, suggesting the types of damage accumulating differs between young and old. The DNA repair genes upregulated in old animals point to accumulation of replication-dependent DNA double strand breaks (DSB). Expression data is consistent with loss of apoptosis following DNA damage in old animals. These data suggest DNA damage responses differ greatly in young and old animals. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Simon, Kirk; Cabelof, Diane C.] Wayne State Univ, Dept Nutr & Food Sci, Detroit, MI 48084 USA. [Mukundan, Anju; Dombkowski, Alan A.] Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48084 USA. [Dewundara, Samantha] Wayne State Univ, Karmanos Canc Ctr, Detroit, MI 48084 USA. [Van Remmen, Holly] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. [Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cell & Struct Biol, San Antonio, TX 78229 USA. [Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. RP Cabelof, DC (reprint author), Wayne State Univ, Dept Nutr & Food Sci, Detroit, MI 48084 USA. EM d.cabelof@wayne.edu FU NIH [1F32-ES013643]; American Federation for Aging Research (DCC); Microarray and Bioinformatics Facility Core of the Environmental Health Sciences Center at Wayne State University [P30 ES06639] FX This work was supported by NIH 1F32-ES013643 (DCC) and American Federation for Aging Research (DCC). Microarray and bioinformatics work was facilitated by the Microarray and Bioinformatics Facility Core of the Environmental Health Sciences Center at Wayne State University (NIEHS Center Grant P30 ES06639). We would like to thank Dr. Thierry Soussi for his input on p53-target genes. We would also like to thank Anna Unnikrishnan, Sridevi Salagrama and Daniela Cukovic for their technical assistance. NR 50 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD SEP PY 2009 VL 130 IS 9 BP 637 EP 647 DI 10.1016/j.mad.2009.07.007 PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 504QL UT WOS:000270632000008 PM 19679149 ER PT J AU Henke, RM Zaslavsky, AM McGuire, TG Ayaian, JZ Rubenstein, LV AF Henke, Rachel M. Zaslavsky, Alan M. McGuire, Thomas G. Ayaian, John Z. Rubenstein, Lisa V. TI Clinical Inertia in Depression Treatment SO MEDICAL CARE LA English DT Article DE depression; clinical inertia; evidence-based medicine; physician practice patterns ID PRIMARY-CARE CLINICIAN; QUALITY IMPROVEMENT; STATISTICAL DISCRIMINATION; TREATING DEPRESSION; COLLABORATIVE CARE; COMPETING DEMANDS; RANDOMIZED-TRIAL; COMMUNICATION; OUTCOMES; PATIENT AB Objective: To explore reasons for clinical inertia in the management of persistent depression symptoms. Research Design: We characterized patterns of treatment adjustment in primary care and their relation to the patient's clinical condition by modeling transition to a given treatment "state" conditional on the current state of treatment. We assessed associations of patient, clinician, and practice barriers with adjustment decisions. Subjects: Survey data on patients in active care for major depression were collected at 6-month intervals over a 2-year period for the quality improvement for depression (QID) studies. Measures: Patient and clinician characteristics were collected at baseline. Depression severity and treatment were measured at each interval. Results: Approximately, one-third of the observation periods ending with less than a full response resulted in an adjustment recommendation. Clinicians often respond correctly to the combination of severe depression symptoms and less than maximal treatment by changing the treatment. Appropriate adjustment is less common, however, in management of less severely depressed patients who do not improve after starting treatment, particularly if their care already meets minimal treatment intensity guidelines. Conclusions: Our findings suggest that quality improvement efforts should focus on promoting appropriate adjustments for patients with persistent depression symptoms, particularly those with less severe depression. C1 [Henke, Rachel M.] Thomson Reuters Healthcare, Cambridge, MA USA. [Zaslavsky, Alan M.; McGuire, Thomas G.; Ayaian, John Z.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Rubenstein, Lisa V.] VA Greater Los Angeles, Los Angeles, CA USA. [Rubenstein, Lisa V.] RAND, Santa Monica, CA USA. RP Henke, RM (reprint author), Thomson Reuters, 150 Cambridge Pk Dr, Cambridge, MA 02140 USA. EM rachel.henke@thomsonreuters.com FU F31 [F31 MH75719, R01 MH068260] FX Supported by grants from the National Institute of Mental Health (F31 MH75719; R01 MH068260). NR 48 TC 15 Z9 16 U1 0 U2 2 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 SEP PY 2009 VL 47 IS 9 BP 959 EP 967 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 489GH UT WOS:000269407700005 PM 19704353 ER PT J AU Marsteller, JA Burton, L Mader, SL Naughton, B Burl, J Guido, S Greenough, WB Steinwachs, D Clark, R Leff, B AF Marsteller, Jill A. Burton, Lynda Mader, Scott L. Naughton, Bruce Burl, Jeffrey Guido, Susan Greenough, William B., III Steinwachs, Donald Clark, Rebecca Leff, Bruce TI Health Care Provider Evaluation of a Substitutive Model of Hospital at Home SO MEDICAL CARE LA English DT Article DE hospital care; home; provider evaluation; provider satisfaction ID OLDER PATIENTS AB Objective: To evaluate Hospital at Home (HaH), a substitute for inpatient care, from the perspectives of participating providers. Research Design: Multivariate general estimating equations regression analyses of a patient-specific survey of providers delivering HaH care in a prospective, nonrandomized clinical trial. Subjects: Eleven physicians and 26 nurses employed in 3 Medicare-Advantage plans and I Veterans Administration medical center. Measures: Problems with care; benefits; problem-free index. Results: Case response rates were 95% and 82% for physicians and nurses, respectively. The overall problem-free index was high (mean 4.4, median 5, scale 1-5). "Major" problems were cited for 14 of 84 patients (17%), most relating to logistic issues without adverse patient outcomes. Positive effects included quicker patient functional recovery, greater opportunities for patient teaching, and increased communication with family caregivers. In multivariate analysis, the problem-free index was lower for nurses compared with physicians in one site; for patients with cellulitis; and for patients with a higher acuity (APACHE II) score. HaH physicians and nurses differed in their judgments of hours of continuous nursing required by patients. Conclusions: The health care provider evaluation of substitutive HaH care was positive, providing support for the viability of this innovative model of care. Without provider support, no new model of care will survive. These findings also provide insight into areas to attend to in implementation. Organizations considering adoption of the HaH should monitor provider views to promote quality improvement in HaH. C1 [Leff, Bruce] Johns Hopkins Univ, Sch Med, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Mader, Scott L.] Portland VA Med Ctr, Portland, OR USA. [Mader, Scott L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Naughton, Bruce] SUNY Buffalo, Buffalo, NY 14260 USA. [Burl, Jeffrey] Fallon Clin Inc, Worcester, MA USA. RP Marsteller, JA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 624 N Broadway,Room 433 Hampton House, Baltimore, MD 21205 USA. EM jmarstel@jhsph.edu NR 12 TC 4 Z9 4 U1 1 U2 2 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 SEP PY 2009 VL 47 IS 9 BP 979 EP 985 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 489GH UT WOS:000269407700007 PM 19704355 ER PT J AU Hausmann, LRM Ibrahim, SA Mehrotra, A Nsa, W Bratzler, DW Mor, MK Fine, MJ AF Hausmann, Leslie R. M. Ibrahim, Said A. Mehrotra, Ateev Nsa, Wato Bratzler, Dale W. Mor, Maria K. Fine, Michael J. TI Racial and Ethnic Disparities in Pneumonia Treatment and Mortality SO MEDICAL CARE LA English DT Article DE health disparities; pneumonia; quality of care ID COMMUNITY-ACQUIRED PNEUMONIA; QUALITY-OF-CARE; COST-EFFECTIVENESS; HOSPITAL CHARACTERISTICS; HEALTH-CARE; ELDERLY-PATIENTS; WORKING ADULTS; BLACK PATIENTS; VACCINATION; INFLUENZA AB Background: The extent to which racial/ethnic disparities in pneumonia care occur within or between hospitals is unclear. Objective: Examine within and between-hospital racial/ethnic disparities in quality indicators and mortality for patients hospitalized for pneumonia. Research Design: Retrospective cohort Study. Subjects: A total of 1,183,753 non-Hispanic white, African American, and Hispanic adults hospitalized for pneumonia between January 2005 and June 2006. Measures: Eight pneumonia care quality indicators and in-hospital mortality. Results: Performance rates for the 8 quality indicators ranged from 99.4% (oxygenation assessment within 24 hours) to 60.2% (influenza vaccination). Overall hospital mortality was 4.1%. African American and Hispanic patients were less likely to receive pneumococcal and influenza vaccinations, smoking cessation counseling, and first dose of antibiotic within 4 hours than white patients at the same hospital (ORs = 0.65-0.95). Patients at hospitals with the racial composition of those attended by average African Americans and Hispanics were less likely to receive all indicators except blood culture within 24 hours than patients at hospitals with the racial composition of those attended by average whites. Hospital mortality was higher for African Americans (OR = 1.05; 95% Cl = 1.02, 1.09) and lower for Hispanics (OR = 0.85; 95% Cl = 0.81, 0.89) than for whites within the same hospital. Mortality for patients at hospitals with the racial composition of those attended by average African Americans (OR = 1.21; 95% Cl = 1.18, 1.25) or Hispanics (OR = 1.18; 95% Cl = 1.14, 1.23) was higher than for patients at hospitals with the racial composition of those attended by average whites. Conclusions: Racial/ethnic disparities in pneumonia treatment and mortality are larger and more consistent between hospitals than within hospitals. C1 [Hausmann, Leslie R. M.; Ibrahim, Said A.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Ibrahim, Said A.; Mehrotra, Ateev; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Ibrahim, Said A.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Mehrotra, Ateev] RAND Hlth, Pittsburgh, PA USA. [Nsa, Wato; Bratzler, Dale W.] Oklahoma Fdn Med Qual, Oklahoma City, OK USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM leslie.hausmann@gmail.com FU National Institutes of Musculoskeletal and Skin Disorders [RCD 06-287, 1K24AR055259-01]; National Center for Research Resources [KL2-R-R024154-01] FX Supported by resources and the use of facilities at the Veterans Affairs Pittsburgh Healthcare System in Pittsburgh, PA and by VA Health Services Research and Development Career Development Award RCD 06-287 (to L.R.M.H.), K24 Award (1K24AR055259-01) from the National Institutes of Musculoskeletal and Skin Disorders (to S.A.I., the recipient of a VA Health Services Research and Development Award and the Harold Amos Robert Wood Johnson Scholar Award). A.M.'s salary was supported by a career development award from the National Center for Research Resources, a component of the National Institutes of Health (KL2-R-R024154-01). NR 44 TC 17 Z9 17 U1 1 U2 2 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 SEP PY 2009 VL 47 IS 9 BP 1009 EP 1017 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 489GH UT WOS:000269407700011 PM 19648832 ER PT J AU Lutfey, KE Link, CL Marceau, LD Grant, RW Adams, A Arber, S Siegrist, J Bonte, M von dem Knesebeck, O McKinlay, JB AF Lutfey, Karen E. Link, Carol L. Marceau, Lisa D. Grant, Richard W. Adams, Ann Arber, Sora Siegrist, Johannes Boente, Markus von dem Knesebeck, Olaf McKinlay, John B. TI Diagnostic Certainty as a Source of Medical Practice Variation in Coronary Heart Disease: Results from a Cross-National Experiment of Clinical Decision Making SO MEDICAL DECISION MAKING LA English DT Article DE clinical decision making; medical practice variation; health disparities ID HEALTH-CARE; STATISTICAL DISCRIMINATION; PATIENT CHARACTERISTICS; STANDARDIZED PATIENTS; FACTORIAL EXPERIMENT; GENDER DISPARITIES; UNITED-STATES; MANAGED CARE; RISK-FACTORS; DOCTORS AB The authors examined physician diagnostic certainty as one reason for cross-notional medical practice variation. Data are from a factorial experiment conducted in the United States, the United Kingdom, and Germany, estimating 384 generalist physicians. diagnostic and treatment decisions for videotaped vignettes of actor patients depicting a presentation consistent with coronary heart disease (CHD). Despite identical vignette presentations, the authors observed significant differences across health care systems, with US physicians being the most certain and German physicians the least certain (P < 0.0001). Physicians were least certain of a CHD diagnoses when patients were younger and female (P < 0.0086), and there was additional variation by health core system (as represented by country) depending on patient age (P < 0.0100) and race (P < 0.0021). Certainty was positively correlated with several clinical actions. including test ordering prescriptions, referrals to specialists, and time to follow-up. C1 [Lutfey, Karen E.; Link, Carol L.; Marceau, Lisa D.; McKinlay, John B.] New England Res Inst, Watertown, MA 02472 USA. [Grant, Richard W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grant, Richard W.] Harvard Univ, Sch Med, Boston, MA USA. [Adams, Ann] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Arber, Sora] Univ Surrey, Guildford GU2 5XH, Surrey, England. [Siegrist, Johannes] Univ Dusseldorf, Dusseldorf, Germany. [Boente, Markus; von dem Knesebeck, Olaf] Univ Hamburg, Hamburg, Germany. RP Lutfey, KE (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM klutfey@neriscience.com OI Grant, Richard/0000-0002-6164-8025 FU NIA NIH HHS [AG16747, R01 AG016747] NR 56 TC 9 Z9 9 U1 3 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2009 VL 29 IS 5 BP 606 EP 618 DI 10.1177/0272989X09331811 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 505GF UT WOS:000270679300007 PM 19470719 ER PT J AU Bismuth, J Chai, H Lin, PH Yao, QZ Chen, CY AF Bismuth, Jean Chai, Hong Lin, Peter H. Yao, Qizhi Chen, Changyi TI Lactosylceramide causes endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells SO MEDICAL SCIENCE MONITOR LA English DT Article DE lactosylceramide; endothelial dysfunction; eNOS; coronary artery; oxidative stress; NOX4; calatase ID PROTEASE INHIBITOR RITONAVIR; NITRIC-OXIDE SYNTHASE; INDUCED VASCULAR DYSFUNCTION; LOW-DENSITY-LIPOPROTEIN; SUPEROXIDE PRODUCTION; PULMONARY-ARTERIES; CERAMIDE; SPHINGOMYELINASE; ATHEROSCLEROSIS; ACTIVATION AB Background: Lactosylceramide (LacCer) is a member of the glycosphingolipid family, which has been implicated in the atherogenic process. The goal of this study was to determine the effects and molecular mechanisms of LacCer on endothelial functions in porcine coronary arteries and human coronary endothelial cells (HCAECs). Material/Methods: The vessel rings and HCAECs were treated with different concentrations of LacCer for 24 hours. Vasomotor function was studied using a myograph tension system in response to thromboxane A2 analog U46619, bradykinin and sodium nitroprusside (SNP). Superoxide anion production was determined using lucigenin-enhanced chemiluminescence. The expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase subunit NOX4 and catalase was determined by real-time PCR. Results: LacCer (0.1, 1 and 10 mu M) significantly decreased endothelium-dependent vasorelaxation (bradykinin) in porcine coronary artery rings in a concentration-dependent manner compared with untreated controls (P<0.05). High concentration of LacCer (10 mu M) also reduced endothelium-independent vasorelaxation (SNP). However, LacCer did not affect vessel contraction (U46619). Antioxidant selenomethionine (SeMet) effectively reversed LacCer-induced endothelial dysfunction in the vessel rings. Furthermore, LacCer significantly increased superoxide anion production in the vessel rings in a concentration-dependent manner compared with untreated controls (P<0.05). In response to LacCer treatment, NOX4 mRNA levels were significantly increased, while the expression of catalase and eNOS was significantly decreased in HCAECs compared with controls (P<0.05). Conclusions: LacCer causes endothelial dysfunction with potential mechanisms of the down-regulation of eNOS and increase of oxidative stress due to the activation of NADPH oxidase and inhibition of internal antioxidant catalase. This study suggests that LacCer may represent a risk factor to the vascular system and antioxidant SeMet may have clinical applications for prevention of vascular disease. C1 [Bismuth, Jean; Chai, Hong; Lin, Peter H.; Yao, Qizhi; Chen, Changyi] Baylor Coll Med, Michael E DeBakey Dept Surg, Mol Surg Res Ctr, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. [Lin, Peter H.; Yao, Qizhi; Chen, Changyi] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Chen, CY (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Mol Surg Res Ctr, Div Vasc Surg & Endovasc Therapy, 1 Baylor Plaza,Mail Stop BCM 390, Houston, TX 77030 USA. EM jchen@bcm.tmc.edu FU NHLBI NIH HHS [R01 HL072716-03, R01 HL072716, K08 HL076345, HL72716, HL65916, HL076345, R01 HL065916, R01 HL065916-05, K08 HL076345-04] NR 21 TC 10 Z9 10 U1 0 U2 1 PU INT SCIENTIFIC LITERATURE, INC PI ALBERTSON PA 1125 WILLIS AVE, ALBERTSON, NY 11507 USA SN 1234-1010 J9 MED SCI MONITOR JI Med. Sci. Monitor PD SEP PY 2009 VL 15 IS 9 BP BR270 EP BR274 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 502XP UT WOS:000270494200005 PM 19721395 ER PT J AU Bailey, A AF Bailey, Allison TI Menopause and physical fitness SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID TAI-CHI; MUSCLE STRENGTH; ELDERLY-WOMEN; OLDER WOMEN; POSTMENOPAUSAL WOMEN; HORMONE REPLACEMENT; GRIP STRENGTH; PERFORMANCE; BALANCE; HEALTH C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bailey, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 24 TC 0 Z9 1 U1 1 U2 4 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 SEP-OCT PY 2009 VL 16 IS 5 BP 856 EP 857 DI 10.1097/gme.0b013e3181b0d018 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 493AZ UT WOS:000269706800006 PM 19574934 ER PT J AU Grady, D Macer, J Kristof, M Shen, H Tagliaferri, M Creasman, J AF Grady, Deborah Macer, Judith Kristof, Margaret Shen, Hui Tagliaferri, Mary Creasman, Jennifer TI Is a shorter hot flash diary just as good as a 7-day diary? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Menopause; Hot flashes; Measurement; Diary ID FLUSHES; TRIAL AB Objective: In randomized trials, the most common way to measure the effect of treatment on the frequency and severity of menopausal hot flashes is a 7-day self-reported diary. However, adherence with completing the hot flash diary in real time may be poor, and completing a diary is cumbersome for study participants. Our objective was to determine if a shorter diary for recording self-reported hot flashes is as accurate and precise as the traditional 7-day diary. Methods: Using cross-sectional data from a multicenter randomized clinical trial of an herbal preparation (MF101, an estrogen receptor beta-selective agonist for treatment of menopausal hot flashes), we compared findings based on shorter diaries with findings based on a 7-day diary. Results: With 3 days of diary keeping, the mean number of hot flashes per day and mean severity were almost identical to the means based on the 7-day diary, the SDs of the means were almost identical, and the intraclass correlations were almost perfect. The difference in the mean number of hot flashes per day compared with the 7-day diary was only 12% of one hot flash. Data from a different clinical trial revealed similar correspondence between the findings of a 3- and 7-day diary. Conclusions: In our study, the optimal duration of diary keeping to record menopausal hot flashes seems to be 3 days. In addition to being as good as a 7-day diary, a 3-day diary would be less burden on study participants and research staff and less expensive. C1 [Grady, Deborah] Univ Calif San Francisco, Womens Hlth Clin Res Ctr, San Francisco, CA 94115 USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. [Tagliaferri, Mary] Bionovo, Emeryville, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Womens Hlth Clin Res Ctr, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM Deborah.Grady@ucsf.edu FU Bionovo FX Bionovo funded the phase 2 clinical trial from which the data was used for this article. NR 7 TC 2 Z9 2 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 SEP-OCT PY 2009 VL 16 IS 5 BP 932 EP 936 DI 10.1097/gme.0b013e3181a4f558 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 493AZ UT WOS:000269706800017 PM 19421075 ER PT J AU Conway, B Evans, RW Fried, L Kelsey, S Edmundowicz, D Orchard, TJ AF Conway, Baqiyyah Evans, Rhobert W. Fried, Linda Kelsey, Sheryl Edmundowicz, Daniel Orchard, Trevor J. TI Free fatty acids are associated with pulse pressure in women, but not men, with type 1 diabetes mellitus SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID GENDER-RELATED DIFFERENCES; CORONARY-ARTERY-DISEASE; COUNTERREGULATORY RESPONSES; AORTIC STIFFNESS; BLOOD-GLUCOSE; FOLLOW-UP; HYPOGLYCEMIA; METABOLISM; RISK; GLUCONEOGENESIS AB Cardiovascular disease (CVD) is the leading cause of death in type 1 diabetes mellitus (T1D). Pulse pressure, a measure of arterial stiffness, is elevated in T1D and associated with CVD. Free fatty acids (FFAs), elevated in women and abdominal adiposity, are also elevated in T1D and CVD. We thus examined the association of fasting FFAs with pulse pressure and coronary artery calcification (CAC, a marker of coronary atherosclerotic burden) in an adult population (n = 150) of childhood-onset T1D and whether any such associations varied by abdominal adiposity and sex. Mean age and diabetes duration were 42 and 33 years, respectively, when CAC, visceral abdominal adiposity (VAT), and subcutaneous abdominal adiposity (SAT) were determined by electron beam tomography. Free fatty acids were determined by in vitro colorimetry. Pulse pressure was calculated as systolic blood pressure minus diastolic blood pressure. Free fatty acids were log transformed before analyses, and all analyses were controlled for serum albumin. Free fatty acids were associated with pulse pressure in women (r = 0.24, P = .04), but not in men (r = 0.07, P = .55). An interaction for the prediction of pulse pressure was noted between FFAs and both VAT (P = .03) and SAT (P = .008) in women, but only a marginal interaction with SAT (P = .09) and no interaction for VAT (P = .40) with FFAs were observed in men. In multivariable linear regression analysis allowing for serum albumin, age, height, heart rate, albumin excretion rate, hemoglobin A(1c), high-density lipoprotein cholesterol, hypertension medication use, FFAs, SAT, and the interaction between FFAs and SAT, the interaction between FFAs and SAT remained associated with pulse pressure in women (FFAs, P = .04; interaction term, P = .03), but not: men (FFAs, P = .32; interaction term, P = .32). FFAs showed no association with log-transformed CAC. Although FFAs were not associated with CAC in either sex, they were associated with pulse pressure in women and their effect appeared to vary by abdominal adiposity, particularly SAT. This finding might help explain the loss of the sex difference in CVD in T1D. (C) 2009 Elsevier Inc. All rights reserved. C1 [Conway, Baqiyyah; Evans, Rhobert W.; Kelsey, Sheryl; Orchard, Trevor J.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Fried, Linda] VA Pittsburgh Healthcare Syst, Univ Drive Div, Pittsburgh, PA 15240 USA. [Edmundowicz, Daniel] Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15213 USA. RP Orchard, TJ (reprint author), Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. EM orchardt@edc.pitt.edu OI orchard, trevor/0000-0001-9552-3215 FU National Institutes of Health [DK34818] FX This research was supported by National Institutes of Health grant DK34818. The authors would like to thank Beth Hauth for her help in assaying the FFAs. Finally, we would like to thank the EDC study participants for their dedicated participation in this research. NR 45 TC 4 Z9 4 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 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2009 VL 58 IS 9 BP 1215 EP 1221 DI 10.1016/j.metabol.2009.03.010 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 487XB UT WOS:000269310300002 PM 19570556 ER PT J AU Lesic, B Starkey, M He, J Hazan, R Rahme, LG AF Lesic, B. Starkey, M. He, J. Hazan, R. Rahme, L. G. TI Quorum sensing differentially regulates Pseudomonas aeruginosa type VI secretion locus I and homologous loci II and III, which are required for pathogenesis SO MICROBIOLOGY-SGM LA English DT Article ID PROTEIN SECRETION; VIRULENCE FACTORS; INTRACELLULAR GROWTH; EDWARDSIELLA-TARDA; PLANT HOSTS; SYSTEM; IDENTIFICATION; GENES; PATHOGENICITY; INFECTION AB Pseudomonas aeruginosa harbours three type VI secretion (T6S) loci. Although HSI-I has been partially studied, limited knowledge is available on the homologous loci HSI-II and We show that quorum sensing (OS) differentially regulates the expression of genes at all three loci. HSI-I-associated gene expression is suppressed by both the homoserine lactone transcription factor LasR and the 4-hydroxy-2-alkylquinoline (HAQ) transcriptional regulator MvfR. Conversely, both HSI-II and HSI-III loci are positively controlled by LasR and MvfR. PqsE, a key component of the MvfR regulon, is required for the expression of part of HSI-III but not HSI-II, and previously identified inhibitors of HAQ biosynthesis significantly downregulate HSI-II and -III gene expression. Animal and plant infection studies reveal that both HSI-II and -III play important roles in pathogenesis. Furthermore, analysis of a double Delta HSI-II : : III mutant suggests that these loci functionally compensate for one another in virulence. This study illustrates the contribution of the QS systems to T6S gene regulation and reveals the importance of HSI-II and -III in mediating P. aeruginosa pathogenesis. Moreover, this work provides new insights into the design and development of selective compounds that may restrict human P. aeruginosa and possibly other clinical infections. C1 [Lesic, B.; Starkey, M.; He, J.; Hazan, R.; Rahme, L. G.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lesic, B.; Starkey, M.; He, J.; Hazan, R.; Rahme, L. G.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Lesic, B.; Starkey, M.; He, J.; Hazan, R.; Rahme, L. G.] Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM rahme@molbio.mgh.harvard.edu FU National Institutes of Health [AI063433]; Shriners [8770, 8606] FX This work was supported by the National Institutes of Health grant AI063433 and Shriners grant 8770 to L. G. R. M. S. was supported by Shriners Research Post-doctoral Fellowship #8606. We thank Dionyssios Mintzopoulos for assistance with the statistical analysis and Gloria Soberon-Chavez, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, for the pMT1 plasmid. NR 50 TC 70 Z9 71 U1 2 U2 19 PU MICROBIOLOGY SOC PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER ST, LONDON WC1N 2JU, ERKS, ENGLAND SN 1350-0872 EI 1465-2080 J9 MICROBIOL-SGM JI Microbiology-(UK) PD SEP PY 2009 VL 155 BP 2845 EP 2855 DI 10.1099/mic.0.029082-0 PN 9 PG 11 WC Microbiology SC Microbiology GA 499YZ UT WOS:000270264300005 PM 19497948 ER PT J AU Gibson, TB Lee, TA Vogeli, CS Hidalgo, J Carls, GS Sredl, K DesHarnais, S Marder, WD Weiss, KB Williams, TV Shields, AE AF Gibson, Teresa B. Lee, Todd A. Vogeli, Christine S. Hidalgo, Julia Carls, Ginger Smith Sredl, Katherine DesHarnais, Susan Marder, William D. Weiss, Kevin B. Williams, Thomas V. Shields, Alexandra E. TI A Four-System Comparison of Patients With Chronic Illness: The Military Health System, Veterans Health Administration, Medicaid, and Commercial Plans SO MILITARY MEDICINE LA English DT Article ID OUTCOMES AB We compared chronic care utilization in four major health systems in the U.S.: the military health system (TRICARE), the Department of Veterans Affairs (VA), Medicaid, and employer-sponsored commercial plans. Prevalence rates and key performance indicators were constructed from administrative data in federal fiscal year 2003 for eight chronic conditions: hypertension, major depression, diabetes, tobacco dependence, ischemic heart disease, severe mental illness, persistent asthma, and stroke. Continuously enrolled beneficiaries under 65 years old were studied: TRICARE (N = 2,963,987), VA (N = 2,114,739), Medicaid enrollees in five states (N = 5,554,974), and commercial insurance (N = 5,212,833). Condition-specific adjusted prevalence rates and measures were compared using the standardized rate ratio. For the majority of the conditions, the estimated prevalence rates were highest in the VA and Medicaid populations. Prevalence rates were generally lower in TRICARE and commercial plans. Medicaid beneficiaries had the highest hospitalization rates in four of the six conditions where hospitalization rates were measured. These results provide empirical evidence of differences in chronically ill patient populations in several of the major U.S. health insurance systems. C1 [Gibson, Teresa B.] Thomson Reuters, Ann Arbor, MI 48108 USA. [Lee, Todd A.; Weiss, Kevin B.] Edward Hines Jr VA Hosp, Hines, IL 60141 USA. [Vogeli, Christine S.; Shields, Alexandra E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hidalgo, Julia] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC 20006 USA. [Carls, Ginger Smith; Sredl, Katherine] Thomson Reuters, Santa Barbara, CA 93111 USA. [DesHarnais, Susan] Thomas Jefferson Univ, Sch Populat Hlth, Philadelphia, PA 19107 USA. [Marder, William D.] Thomson Reuters, Cambridge, MA 02140 USA. [Williams, Thomas V.] US Dept Def, Falls Church, VA 22041 USA. RP Gibson, TB (reprint author), Thomson Reuters, 777 E Eisenhower Pkwy, Ann Arbor, MI 48108 USA. OI Marder, William/0000-0002-7198-6933 FU Department of Defense [HHSP23320045013XI] FX We thank Eva Wiu for programming assistance and Mary McGinn-Shapiro for research assistance. This study was funded by the Department of Defense under HHSP23320045013XI. NR 18 TC 9 Z9 9 U1 0 U2 0 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD SEP PY 2009 VL 174 IS 9 BP 936 EP 943 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 601LH UT WOS:000278060400007 PM 19780368 ER PT J AU Chen, W Zhang, J Zhang, T Li, HX Wang, WY Xia, ZN Wang, M AF Chen, Wei Zhang, Juan Zhang, Tao Li, Haixin Wang, Wenyi Xia, Zhinan Wang, Min TI Improved Isolation of Anti-rhTNF-alpha scFvs from Phage Display Library by Bioinformatics SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE TNF-alpha; scFv; Phage display; Bioinformatics; Homology modeling; Docking ID FILAMENTOUS PHAGE; HIGH SPECIFICITY; HUMAN-ANTIBODIES; PROTEIN-DOCKING; TNF-ALPHA; RECOGNITION; ALGORITHM; SURFACE; SITE; WEB AB Phage display technology has been widely used to isolate antibodies with specific properties. The objective of this study was to isolate anti-rhTNF-alpha scFvs from phage display library. However, the inserted genes of eluted phages were either incorrect or truncated. In order to address this issue, bioinformatics was applied to facilitate the screening of the eluted phages. The alignment of the sequencing results was performed with the software ClustalW. The gene of scFv (F6) was assembled by ligating together the identical VH and VL fragments and then analyzed by using program BLASTX. F6 was identified to share 80% sequence identity with a human anti-TNF-alpha scFv. Subsequently, the conformation of F6 binding to hTNF-alpha predicted by docking assay showed that F6 could bind to hTNF-alpha via the six CDRs. Finally, ELISA assay and Western blot analysis indicated that F6 might bind to rhTNF-alpha specifically. Biological assay demonstrated that F6 might neutralize rhTNF-alpha-induced cytotoxicity in L929 cells. In conclusion, F6 could be a candidate for further investigation, based on the experimental data and the prediction by bioinformatics. C1 [Chen, Wei; Zhang, Juan; Zhang, Tao; Li, Haixin; Wang, Wenyi; Wang, Min] China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing 210009, Peoples R China. [Xia, Zhinan] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP Wang, M (reprint author), China Pharmaceut Univ, Sch Life Sci & Technol, 153 Tong Jia Xiang 24, Nanjing 210009, Peoples R China. EM minwang@cpu.edu.cn NR 28 TC 4 Z9 4 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD SEP PY 2009 VL 43 IS 1 BP 20 EP 28 DI 10.1007/s12033-009-9172-x PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 486OG UT WOS:000269205900004 PM 19412671 ER PT J AU Zhang, J Song, YH Brannigan, BW Wahrer, DCR Schiripo, TA Harris, PL Haserlat, SM Ulkus, LE Shannon, KM Garber, JE Freedman, ML Henderson, BE Zou, L Sgroi, DC Haber, DA Bell, DW AF Zhang, Jianmin Song, Young-Han Brannigan, Brian W. Wahrer, Doke C. R. Schiripo, Taryn A. Harris, Patricia L. Haserlat, Sara M. Ulkus, Lindsey E. Shannon, Kristen M. Garber, Judy E. Freedman, Matthew L. Henderson, Brian E. Zou, Lee Sgroi, Dennis C. Haber, Daniel A. Bell, Daphne W. TI Prevalence and Functional Analysis of Sequence Variants in the ATR Checkpoint Mediator Claspin SO MOLECULAR CANCER RESEARCH LA English DT Article ID CANCER SUSCEPTIBILITY GENE; REPEATED PHOSPHOPEPTIDE MOTIFS; BREAST-CANCER; DNA-DAMAGE; P53 MUTATIONS; CHK1; ACTIVATION; MRC1; RECOVERY; KINASE AB Mutational inactivation of genes controlling the DNA-damage response contributes to cancer susceptibility within families and within the general population as well as to sporadic tumorigenesis. Claspin (CLSPN) encodes a recently recognized mediator protein essential for the ATR and CHK1-dependent checkpoint elicited by replicative stress or the presence of ssDNA. Here, we describe a study to determine whether mutational disruption of CLSPN contributes to cancer susceptibility and sporadic tumorigenesis. We resequenced CLSPN from the germline of selected cancer families with a history of breast cancer (n = 25) or a multicancer phenotype (n = 46) as well as from a panel of sporadic cancer cell lines (n = 52) derived from a variety of tumor types. Eight nonsynonymous variants, including a recurrent mutation, were identified from the germline of two cancer-prone individuals and five cancer cell lines of breast, ovarian, and hematopoietic origin. None of the variants was present within population controls. In contrast, mutations were rare within genes encoding the CLSPN-interacting protein ATR and its binding partner ATRIP. One variant of CLSPN, encoding the 1783S missense mutation, was defective in its ability to mediate CHK1 phosphorylation following DNA damage and was unable to rescue sensitivity to replicative stress in CLSPN-depleted cells. Taken together, these observations raise the possibility that CLSPN may encode a component of the DNA-damage response pathway that is targeted by mutations in human cancers, suggesting the need for larger population-based studies to investigate whether CLSPN variants contribute to cancer susceptibility. (Mol Cancer Res 2009;7(9):1510-6) C1 [Zhang, Jianmin; Song, Young-Han; Brannigan, Brian W.; Wahrer, Doke C. R.; Schiripo, Taryn A.; Harris, Patricia L.; Haserlat, Sara M.; Ulkus, Lindsey E.; Shannon, Kristen M.; Zou, Lee; Sgroi, Dennis C.; Haber, Daniel A.; Bell, Daphne W.] MGH Canc Ctr, Charlestown, MA 02129 USA. [Zhang, Jianmin; Song, Young-Han; Brannigan, Brian W.; Wahrer, Doke C. R.; Schiripo, Taryn A.; Harris, Patricia L.; Haserlat, Sara M.; Ulkus, Lindsey E.; Shannon, Kristen M.; Zou, Lee; Sgroi, Dennis C.; Haber, Daniel A.; Bell, Daphne W.] Harvard Univ, Sch Med, Charlestown, MA USA. [Freedman, Matthew L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Freedman, Matthew L.] Broad Inst Biomed Res, Boston, MA USA. [Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. RP Haber, DA (reprint author), MGH Canc Ctr, Bldg 149,CNY7,13th St, Charlestown, MA 02129 USA. EM Haber@helix.mgh.harvard.edu OI Song, Young-Han/0000-0002-0758-3654 FU NIH [CA87691]; Research Excellence on Breast Cancer at Massachusetts General Hospital; Avon Products Foundation; AACR-National Foundation for Cancer Research Professorship in Basic Cancer Research; Doris Duke Foundation; NHGRI/NIH Intramural Research Program; Howard Hughes Medical Institute FX Grant support: NIH grant CA87691 (D.A. Haber), the National Cancer Institute Specialized Programs of Research Excellence on Breast Cancer at Massachusetts General Hospital (D.A. Haber), the Avon Products Foundation (D.W. Bell), the AACR-National Foundation for Cancer Research Professorship in Basic Cancer Research (D.A. Haber), the Doris Duke Foundation (D.A. Haber), the NHGRI/NIH Intramural Research Program (D.W. Bell), and by a fellowship from the Howard Hughes Medical Institute (M.L. Freedman). NR 41 TC 4 Z9 4 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD SEP PY 2009 VL 7 IS 9 BP 1510 EP 1516 DI 10.1158/1541-7786.MCR-09-0033 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 496ZM UT WOS:000270019700010 PM 19737971 ER PT J AU Yang, C Schwab, JH Schoenfeld, AJ Hornicek, FJ Wood, KB Nielsen, GP Choy, E Mankin, H Duan, ZF AF Yang, Cao Schwab, Joseph H. Schoenfeld, Andrew J. Hornicek, Francis J. Wood, Kirkham B. Nielsen, G. Petur Choy, Edwin Mankin, Henry Duan, Zhenfeng TI A novel target for treatment of chordoma: signal transducers and activators of transcription 3 SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GROWTH-FACTOR RECEPTOR; BREAST-CANCER CELLS; TERM-FOLLOW-UP; CONSTITUTIVE ACTIVATION; CARCINOMA CELLS; TYROSINE KINASES; PROSTATE-CANCER; SACRAL CHORDOMA; STAT3; APOPTOSIS AB A major obstacle in the effective treatment of chordoma is that there are no identifiable biomarkers capable of predicting prognosis. Recent research has indicated that signal transducers and activators of transcription (Stat3) may be an important prognostic marker in some cancers, but its role in chordoma tumors has not been elucidated. In this study, the expression of Stat3 was evaluated in chordoma tissue microarray that contains 70 chordoma samples. Cells in the tissue microarray showed nuclear staining for phosphorylated Stat3 in all instances. The level of phosphorylated Stat3 expression correlated with the survival and severity of the disease. Three chordoma cell lines were exposed to SD-1029, a novel inhibitor of Stat3 activation. MTT assay showed that the growth of all chordoma cell lines was inhibited by SD-1029. The expression of Stat3 signaling cascade was inhibited in all chordoma cell lines after treatment with SD-1029. The cytotoxicity of the combination of SD-1029 and chemotherapeutic drugs is significantly better than either agent alone. Phosphorylation of Stat3 in chordoma cells in vitro and cellular proliferation in three-dimensional culture were inhibited by SD-1029. In conclusion, the Stat3 pathway is constitutively activated in chordomas and the level of expression may serve as a predictor for prognosis. Blockade of the Stat3 pathway represents a potential strategy for future treatment. [Mol Cancer Ther 200909):2597-605] C1 [Yang, Cao; Schwab, Joseph H.; Schoenfeld, Andrew J.; Hornicek, Francis J.; Wood, Kirkham B.; Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yang, Cao; Schwab, Joseph H.; Hornicek, Francis J.; Choy, Edwin; Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Choy, Edwin] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Choy, Edwin] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 70 Blossom St,GRJ 1115, Boston, MA 02114 USA. EM zduan@partners.org OI Choy, Edwin/0000-0001-9896-8084; Schoenfeld, Andrew/0000-0002-3691-1215 FU Stephan L. Harris Fund; Sarcoma Foundation of America; National Cancer Institute/NIH [R01-CA119617]; Gattegno and Wechsler funds FX Stephan L. Harris Fund, Sarcoma Foundation of America and National Cancer Institute/NIH (Nanotechnology Platform Partnership) grant R01-CA119617 (Z. Duan), and Gattegno and Wechsler funds. NR 51 TC 32 Z9 40 U1 0 U2 4 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 SEP PY 2009 VL 8 IS 9 BP 2597 EP 2605 DI 10.1158/1535-7163.MCT-09-0504 PG 9 WC Oncology SC Oncology GA 496JY UT WOS:000269968900012 PM 19723879 ER PT J AU Frigo, DE Sherk, AB Wittmann, BM Norris, JD Wang, QB Joseph, JD Toner, AP Brown, M McDonnell, DP AF Frigo, Daniel E. Sherk, Andrea B. Wittmann, Bryan M. Norris, John D. Wang, Qianben Joseph, James D. Toner, Aidan P. Brown, Myles McDonnell, Donald P. TI Induction of Kruppel-Like Factor 5 Expression by Androgens Results in Increased CXCR4-Dependent Migration of Prostate Cancer Cells in Vitro SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; TRANSCRIPTION FACTORS; GENE-EXPRESSION; CARCINOMA-CELLS; DOWN-REGULATION; CXCL12 SDF-1; LIGASE AIP4; GROWTH; METASTASIS; PROLIFERATION AB Advanced prostate cancers preferentially metastasize to bone, suggesting that this tissue produces factors that provide a suitable microenvironment for prostate cancer cells. Recently, it has become clear that even in antiandrogen-resistant cancers, the androgen receptor (AR)-signaling axis is required for prostate cancer progression. Therefore, we hypothesized that AR may be involved in the regulation of pathways that are responsible for the homing of prostate cancer cells to select microenvironments. In support of this hypothesis, we have determined that chemokine (C-X-C motif) receptor 4 (CXCR4), the receptor for the chemokine CXCL12, is up-regulated in prostate cancer cells in response to androgens. Given that the levels of CXCL12 are elevated at sites of known prostate cancer metastases such as bone, these results suggest that androgens may influence prostate cancer metastasis. Specifically, we demonstrate that androgens increase the levels of both CXCR4 mRNA and functional protein in LNCaP prostate cancer cells. Importantly, androgens enhanced the migration of LNCaP cells toward a CXCL12 gradient, an effect that could be blocked by the specific CXCR4 antagonist AMD3100. Interestingly, CXCR4 is not directly regulated by androgens but rather is positively up-regulated by Kruppel-like factor 5 (KLF5), a transcription factor that we have shown to be an early, direct target of AR. Further, KLF5 is both required and sufficient for androgen-mediated CXCR4 expression and migration toward CXCL12. Taken together, these findings demonstrate that AR can utilize the CXCL12/CXCR4 axis through induction of KLF5 expression to promote prostate cancer progression and highlight the potential utility of CXCR4 antagonists as prostate cancer therapeutics. (Molecular Endocrinology 23: 1385-1396, 2009) C1 [Frigo, Daniel E.; Sherk, Andrea B.; Wittmann, Bryan M.; Norris, John D.; Joseph, James D.; Toner, Aidan P.; McDonnell, Donald P.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Wang, Qianben] Ohio State Univ, Coll Med, Ctr Comprehens Canc, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. [Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. RP McDonnell, DP (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813, Durham, NC 27710 USA. EM donald.mcdonnell@duke.edu RI Frigo, Daniel/D-1291-2010; Frigo, Daniel/D-7305-2012; Wang, Qianben/E-4267-2011; OI Brown, Myles/0000-0002-8213-1658; Frigo, Daniel/0000-0002-0713-471X FU National Institutes of Health [F32 DK072794, F32 CA119642, R01 CA139818]; Department of Defense [DAMD17-03-1-0569]; FAS Science Challenge FX This work was supported by National Institutes of Health Grants F32 DK072794 (to D. E. F.), F32 CA119642 (to B. M. W.), and R01 CA139818 (to D. P. M.), Department of Defense Grant DAMD17-03-1-0569 (to A. B. S.), and the FAS Science Challenge (to A. P. T). NR 60 TC 41 Z9 42 U1 0 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 2009 VL 23 IS 9 BP 1385 EP 1396 DI 10.1210/me.2009-0010 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488WO UT WOS:000269381200006 PM 19460858 ER PT J AU Harris, DJ Arn, PH Waisbren, SE Lawrence, JZ Lerner-Ellis, JP Berry, G Levy, HL AF Harris, D. J. Arn, P. H. Waisbren, S. E. Lawrence, J. Z. Lerner-Ellis, J. P. Berry, G. Levy, H. L. TI PHENOTYPIC VARIABILITY IN DEFICIENCY OF THE A SUBUNIT OF SUCCINATE-COALIGASE(SUCLG1) SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Harris, D. J.; Waisbren, S. E.; Lawrence, J. Z.; Lerner-Ellis, J. P.; Berry, G.; Levy, H. L.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Harris, D. J.; Waisbren, S. E.; Berry, G.; Levy, H. L.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Lerner-Ellis, J. P.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Arn, P. H.] Nemours Childrens Clin, Jacksonville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 506 BP 95 EP 95 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600405 ER PT J AU Badr, CE Niers, JM Tjon-Kon-Fat, LA Noske, DP Wurdinger, T Tannous, BA AF Badr, Christian E. Niers, Johanna M. Tjon-Kon-Fat, Lee-Ann Noske, David P. Wurdinger, Thomas Tannous, Bakhos A. TI Real-Time Monitoring of Nuclear Factor kappa B Activity in Cultured Cells and in Animal Models SO MOLECULAR IMAGING LA English DT Article ID NECROSIS-FACTOR-ALPHA; HUMAN-IMMUNODEFICIENCY-VIRUS; ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; TRANSCRIPTION FACTORS; CANCER DEVELOPMENT; EXPRESSION; ACTIVATION; GENES; ANGIOGENESIS AB Nuclear factor kappa B (NF-kappa B) is a transcription factor that plays a major role in many human disorders, including immune diseases and cancer. We designed a reporter system based on NF-kappa B responsive promoter elements driving expression of the secreted Gaussia princeps luciferase (Gluc). We show that this bioluminescent reporter is a highly sensitive tool for noninvasive monitoring of the kinetics of NF-kappa B activation and inhibition over time, both in conditioned medium of cultured cells and in the blood and urine of animals. NF-kappa B activation was successfully monitored in real time in endothelial cells in response to tumor angiogenic signaling, as well as in monocytes in response to inflammation. Further, we demonstrated dual blood monitoring of both NF-kappa B activation during tumor development as correlated to tumor formation using the NF-kappa B Gluc reporter, as well as the secreted alkaline phosphatase reporter. This NF-kappa B reporter system provides a powerful tool for monitoring NF-kappa B activity in real time in vitro and in vivo. C1 Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Ctr Canc, VU Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. RP Tannous, BA (reprint author), Massachusetts Gen Hosp East, Mol Neurogenet Lab, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU National Institutes of Health/National Cancer Institute [P50 CA86355-07]; VONK-SEMMY Foundation FX Financial disclosure of reviewers: None reported. NR 59 TC 30 Z9 32 U1 0 U2 6 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD SEP-OCT PY 2009 VL 8 IS 5 BP 278 EP 290 DI 10.2310/7290.2009.00026 PG 13 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 506TU UT WOS:000270800000005 PM 19796605 ER PT J AU Eminli, S Foudi, A Stadtfeld, M Maherali, N Ahfeldt, T Mostoslavsky, G Hock, H Hochedlinger, K AF Eminli, Sarah Foudi, Adlen Stadtfeld, Matthias Maherali, Nimet Ahfeldt, Tim Mostoslavsky, Gustavo Hock, Hanno Hochedlinger, Konrad TI Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells SO NATURE GENETICS LA English DT Article ID HUMAN SOMATIC-CELLS; SMALL-MOLECULE COMPOUNDS; NUCLEAR TRANSFER; DEFINED FACTORS; HUMAN FIBROBLASTS; PROGENITOR CELLS; SELF-RENEWAL; MATURE B; GENERATION; ADULT AB The reprogramming of somatic cells into induced pluripotent stem (iPS) cells upon overexpression of the transcription factors Oct4, Sox2, Klf4 and cMyc is inefficient. It has been assumed that the somatic differentiation state provides a barrier for efficient reprogramming; however, direct evidence for this notion is lacking. Here, we tested the potential of mouse hematopoietic cells at different stages of differentiation to be reprogrammed into iPS cells. We show that hematopoietic stem and progenitor cells give rise to iPS cells up to 300 times more efficiently than terminally differentiated B and T cells do, yielding reprogramming efficiencies of up to 28%. Our data provide evidence that the differentiation stage of the starting cell has a critical influence on the efficiency of reprogramming into iPS cells. Moreover, we identify hematopoietic progenitors as an attractive cell type for applications of iPS cell technology in research and therapy. C1 [Eminli, Sarah; Foudi, Adlen; Stadtfeld, Matthias; Maherali, Nimet; Ahfeldt, Tim; Hock, Hanno; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Eminli, Sarah; Foudi, Adlen; Stadtfeld, Matthias; Maherali, Nimet; Ahfeldt, Tim; Hock, Hanno; Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA USA. [Eminli, Sarah; Stadtfeld, Matthias; Maherali, Nimet; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Eminli, Sarah; Foudi, Adlen; Stadtfeld, Matthias; Maherali, Nimet; Hock, Hanno; Hochedlinger, Konrad] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. [Eminli, Sarah] Free Univ Berlin, Dept Biol Chem & Pharm, D-1000 Berlin, Germany. [Maherali, Nimet] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Ahfeldt, Tim] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Biol 2, Hamburg, Germany. [Mostoslavsky, Gustavo] Boston Univ, Sch Med, Gastroenterol Sect, Dept Med, Boston, MA 02118 USA. [Mostoslavsky, Gustavo] Boston Univ, Ctr Regenerat Med, Boston, MA 02215 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM hock.hanno@mgh.harvard.edu; khochedlinger@helix.mgh.harvard.edu RI Ahfeldt, Tim/E-2935-2017; OI Stadtfeld, Matthias/0000-0002-5852-9906 FU Ellison Foundation to Massachusetts General Hospital FX We thank H. Xie for sharing the C/ EBPa overexpression vector, R. Mostoslavsky for critical reading of the manuscript, L. Prickett and K. Folz- Donahue for help with FACS and P. Follett for help with blastocyst injections. A. F. was the recipient of the Lady Tata Memorial Trust Award. A Postdoctoral Fellowship from Schering Foundation supported M. S. This work was supported by a contribution from the Ellison Foundation to Massachusetts General Hospital start- up funds for H. H., by an American Society of Hematology ( ASH) Scholar Award to H. H. and by the Harvard Stem Cell Institute. Support to K. H. came from the US National Institutes of Health ( NIH) Director's Innovator Award, the Harvard Stem Cell Institute, the Kimmel Foundation and the V Foundation. NR 51 TC 241 Z9 249 U1 3 U2 26 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 SEP PY 2009 VL 41 IS 9 BP 968 EP U29 DI 10.1038/ng.428 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 488WX UT WOS:000269382100007 PM 19668214 ER PT J AU Amundadottir, L Kraft, P Stolzenberg-Solomon, RZ Fuchs, CS Petersen, GM Arslan, AA Bueno-De-Mesquita, HB Gross, M Helzlsouer, K Jacobs, EJ LaCroix, A Zheng, W Albanes, D Bamlet, W Berg, CD Berrino, F Bingham, S Buring, JE Bracci, PM Canzian, F Clavel-Chapelon, F Clipp, S Cotterchio, M de Andrade, M Duell, EJ Fox, JW Gallinger, S Gaziano, JM Giovannucci, EL Goggins, M Gonzalez, CA Hallmans, G Hankinson, SE Hassan, M Holly, EA Hunter, DJ Hutchinson, A Jackson, R Jacobs, KB Jenab, M Kaaks, R Klein, AP Kooperberg, C Kurtz, RC Li, DH Lynch, SM Mandelson, M McWilliams, RR Mendelsohn, JB Michaud, DS Olson, SH Overvad, K Patel, AV Peeters, PHM Rajkovic, A Riboli, E Risch, HA Shu, XO Thomas, G Tobias, GS Trichopoulos, D Van Den Eeden, SK Virtamo, J Wactawski-Wende, J Wolpin, BM Yu, H Yu, K Zeleniuch-Jacquotte, A Chanock, SJ Hartge, P Hoover, RN AF Amundadottir, Laufey Kraft, Peter Stolzenberg-Solomon, Rachael Z. Fuchs, Charles S. Petersen, Gloria M. Arslan, Alan A. Bueno-de-Mesquita, H. Bas Gross, Myron Helzlsouer, Kathy Jacobs, Eric J. LaCroix, Andrea Zheng, Wei Albanes, Demetrius Bamlet, William Berg, Christine D. Berrino, Franco Bingham, Sheila Buring, Julie E. Bracci, Paige M. Canzian, Federico Clavel-Chapelon, Francoise Clipp, Sandra Cotterchio, Michelle de Andrade, Mariza Duell, Eric J. Fox, John W., Jr. Gallinger, Steven Gaziano, J. Michael Giovannucci, Edward L. Goggins, Michael Gonzalez, Carlos A. Hallmans, Goran Hankinson, Susan E. Hassan, Manal Holly, Elizabeth A. Hunter, David J. Hutchinson, Amy Jackson, Rebecca Jacobs, Kevin B. Jenab, Mazda Kaaks, Rudolf Klein, Alison P. Kooperberg, Charles Kurtz, Robert C. Li, Donghui Lynch, Shannon M. Mandelson, Margaret McWilliams, Robert R. Mendelsohn, Julie B. Michaud, Dominique S. Olson, Sara H. Overvad, Kim Patel, Alpa V. Peeters, Petra H. M. Rajkovic, Aleksandar Riboli, Elio Risch, Harvey A. Shu, Xiao-Ou Thomas, Gilles Tobias, Geoffrey S. Trichopoulos, Dimitrios Van Den Eeden, Stephen K. Virtamo, Jarmo Wactawski-Wende, Jean Wolpin, Brian M. Yu, Herbert Yu, Kai Zeleniuch-Jacquotte, Anne Chanock, Stephen J. Hartge, Patricia Hoover, Robert N. TI Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer SO NATURE GENETICS LA English DT Article ID BASE-LINE CHARACTERISTICS; WOMENS HEALTH; BLOOD-GROUP; RISK; DESIGN; GENES; POLYMORPHISMS; RATIONALE; MORTALITY; ALLERGIES AB We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B. C1 [Amundadottir, Laufey; Chanock, Stephen J.] Natl Canc Inst, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlt & Human Serv, Bethesda, MD 20892 USA. [Amundadottir, Laufey; Stolzenberg-Solomon, Rachael Z.; Albanes, Demetrius; Hutchinson, Amy; Mendelsohn, Julie B.; Thomas, Gilles; Tobias, Geoffrey S.; Yu, Kai; Chanock, Stephen J.; Hartge, Patricia; Hoover, Robert N.] Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Kraft, Peter; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Michaud, Dominique S.; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Petersen, Gloria M.; Bamlet, William; de Andrade, Mariza] Mayo Clin, Dept Hlth Sci Res, Coll Med, Rochester, MN USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA. [Helzlsouer, Kathy] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [LaCroix, Andrea; Kooperberg, Charles; Mandelson, Margaret] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Berg, Christine D.] Natl Canc Inst, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Berrino, Franco] Ist Nazl Tumori, Etiol Epidemiol & Prevent Unit, Fdn IRCCS, I-20133 Milan, Italy. [Bingham, Sheila] Univ Cambridge, MRC, Dunn Human Nutr Unit, Cambridge, England. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Canzian, Federico; Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, DKFZ, D-6900 Heidelberg, Germany. [Clavel-Chapelon, Francoise] INSERM, Villejuif, France. [Clavel-Chapelon, Francoise] Inst Gustave Roussy, Villejuif, France. [Clipp, Sandra] Johns Hopkins Bloomberg Sch Publ Hlth, George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA. [Cotterchio, Michelle] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Duell, Eric J.; Jenab, Mazda] Int Agcy Res Canc, F-69372 Lyon, France. [Fox, John W., Jr.] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Oncol, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Pathol, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Med, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA. [Gonzalez, Carlos A.] ICO, Unit Nutr Environm & Canc, Canc Epidemiol Res Programme, Barcelona, Spain. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Hassan, Manal; Li, Donghui] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Hutchinson, Amy; Jacobs, Kevin B.] SAIC Frederick Inc, Core Genotyping Facil, Adv Technol Program, NCI, Frederick, MD USA. [Jackson, Rebecca] Ohio State Univ, Dept Internal Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Jackson, Rebecca] Ohio State Univ, Ctr Clin & Translat Sci, Columbus, OH 43210 USA. [Jacobs, Kevin B.] Bioinformed LLC, Gaithersburg, MD USA. [Klein, Alison P.] Johns Hopkins Med Inst, Dept Epidemiol, Johns Hopkins Bloomberg Sch Publ Hlth, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA. [Lynch, Shannon M.] Natl Canc Inst, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. [Kurtz, Robert C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Mandelson, Margaret] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [McWilliams, Robert R.] Mayo Clin, Dept Oncol, Coll Med, Rochester, MN USA. [Michaud, Dominique S.; Peeters, Petra H. M.; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Dept Cardiol, Aalborg, Denmark. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Dept Clin Epidemiol, Aalborg, Denmark. [Peeters, Petra H. M.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Rajkovic, Aleksandar] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Risch, Harvey A.; Yu, Herbert] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Trichopoulos, Dimitrios] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece. [Van Den Eeden, Stephen K.] No Calif Reg, Div Res, Kaiser Permanente, Oakland, CA USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Chanock, SJ (reprint author), Natl Canc Inst, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlt & Human Serv, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov RI Tobias, Geoffrey/M-4135-2016; Gallinger, Steven/E-4575-2013; Clavel-Chapelon, Francoise/G-6733-2014; Michaud, Dominique/I-5231-2014; Gonzalez, Carlos A/O-4651-2014; Albanes, Demetrius/B-9749-2015; Amundadottir, Laufey/L-7656-2016 OI Tobias, Geoffrey/0000-0002-2878-8253; Duell, Eric J/0000-0001-5256-0163; Gonzalez, Carlos A/0000-0003-2822-9715; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Amundadottir, Laufey/0000-0003-1859-8971 FU Intramural NIH HHS [Z01 CP010193-01]; NCI NIH HHS [P50 CA062924, P50 CA062924-140011, P50 CA062924-150011, P50 CA062924-160011, P50 CA102701, P50 CA102701-08, R01 CA082729, R01 CA097193, R01 CA124908] NR 44 TC 260 Z9 270 U1 2 U2 15 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 SEP PY 2009 VL 41 IS 9 BP 986 EP U47 DI 10.1038/ng.429 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 488WX UT WOS:000269382100009 PM 19648918 ER PT J AU Yip, LD Su, L Sheng, DQ Chang, P Atkinson, M Czesak, M Albert, PR Collier, AR Turley, SJ Fathman, CG Creusot, RJ AF Yip, Linda Su, Leon Sheng, Deqiao Chang, Pearl Atkinson, Mark Czesak, Margaret Albert, Paul R. Collier, Ai-Ris Turley, Shannon J. Fathman, C. Garrison Creusot, Remi J. TI Deaf1 isoforms control the expression of genes encoding peripheral tissue antigens in the pancreatic lymph nodes during type 1 diabetes SO NATURE IMMUNOLOGY LA English DT Article ID THYMIC EPITHELIAL-CELLS; MESSENGER-RNA; SELF; TOLERANCE; PROTEIN; MICE; AUTOIMMUNITY; TRANSCRIPTION; POLYMORPHISM; FIBRONECTIN AB Type 1 diabetes may result from a breakdown in peripheral tolerance that is partially controlled by the expression of peripheral tissue antigens (PTAs) in lymph nodes. Here we show that the transcriptional regulator Deaf1 controls the expression of genes encoding PTAs in the pancreatic lymph nodes (PLNs). The expression of canonical Deaf1 was lower, whereas that of an alternatively spliced variant was higher, during the onset of destructive insulitis in the PLNs of nonobese diabetic (NOD) mice. We identified an equivalent variant Deaf1 isoform in the PLNs of patients with type 1 diabetes. Both the NOD mouse and human Deaf1 variant isoforms suppressed PTA expression by inhibiting the transcriptional activity of canonical Deaf1. Lower PTA expression resulting from the alternative splicing of DEAF1 may contribute to the pathogenesis of type 1 diabetes. C1 [Yip, Linda; Su, Leon; Sheng, Deqiao; Chang, Pearl; Fathman, C. Garrison; Creusot, Remi J.] Stanford Univ, Sch Med, Div Rheumatol & Immunol, Dept Med, Stanford, CA 94305 USA. [Atkinson, Mark] Univ Florida, Dept Pathol, Gainesville, FL 32611 USA. [Czesak, Margaret; Albert, Paul R.] Univ Ottawa, Ottawa Hlth Res Inst Neurosci, Ottawa, ON, Canada. [Czesak, Margaret; Albert, Paul R.] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada. [Collier, Ai-Ris; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Fathman, CG (reprint author), Stanford Univ, Sch Med, Div Rheumatol & Immunol, Dept Med, Stanford, CA 94305 USA. EM cfathman@stanford.edu RI Albert, Paul/E-4804-2010 OI Albert, Paul/0000-0002-1809-3554 FU US National Institutes of Health [U01 DK078123-03, U19-DK 61934, U19-AI050864]; Canadian Institutes of Health Research; American Diabetes Association FX We thank H. Iwai and C. Taylor for technical assistance; J. Visvader (The Walter and Eliza Hall Institute of Medical Research) for Deaf1-deficient mice; and the Network for Pancreatic Organ Donors with Diabetes (Juvenile Diabetes Research Foundation) and the National Disease Research Interchange for human PLNs and spleen samples. Supported by the US National Institutes of Health (U01 DK078123-03, U19-DK 61934 and U19-AI050864 to C. G. F.), the Canadian Institutes of Health Research (P. R. A. and M. C.) and the American Diabetes Association (L. Y.). NR 31 TC 66 Z9 77 U1 0 U2 5 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 SEP PY 2009 VL 10 IS 9 BP 1026 EP U107 DI 10.1038/ni.1773 PG 9 WC Immunology SC Immunology GA 485KV UT WOS:000269120900017 PM 19668219 ER PT J AU Shaw, SY AF Shaw, Stanley Y. TI Molecular imaging in cardiovascular disease: targets and opportunities SO NATURE REVIEWS CARDIOLOGY LA English DT Review ID MATRIX-METALLOPROTEINASE ACTIVITY; POSITRON-EMISSION-TOMOGRAPHY; MRI CONTRAST AGENT; ULTRASMALL SUPERPARAMAGNETIC PARTICLES; CORONARY ATHEROSCLEROTIC PLAQUE; MACROPHAGE SCAVENGER RECEPTOR; CELL-ADHESION MOLECULE-1; IN-VIVO; NONINVASIVE DETECTION; PHOSPHOLIPASE A(2) AB The practice of clinical cardiology employs many imaging techniques for diagnosis, risk stratification and therapeutic monitoring. These imaging modalities largely provide anatomical or structural information, and only indirectly reflect underlying molecular events. Molecular imaging techniques report on entities or processes that can be defined at the molecular, as opposed to the anatomical, level. For example, molecular imaging can reveal the expression or activity of a specific protein, the fate or localization of a biomolecule, or the activity of a biological pathway. This review highlights key processes and molecular targets that are currently being investigated experimentally by molecular imaging probes in vivo. Collectively, these targets have an important role in the development of atherosclerosis and acute plaque rupture, as well as in myocardial disease. Molecular imaging technology is now progressing towards clinical application in humans and has the potential to guide diagnosis, risk assessment and treatment response. imaging-based surrogate end points could speed the development of new drugs, particularly those with novel mechanisms of action. More broadly, by noninvasively reporting on molecular processes in vivo, molecular imaging can reveal how specific proteins or pathways function in their native context, thus contributing to a systems-level understanding of cardiovascular disease biology. C1 [Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Shaw, SY (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Richard B Simches Res Ctr, CPZN 5226,185 Cambridge St, Boston, MA 02114 USA. EM shaw.stanley@mgh.harvard.edu FU NIH; National Heart, Lung and Blood Institute FX S. Y. shaw acknowledges funding from the NIH and National Heart, Lung and Blood Institute. NR 88 TC 22 Z9 26 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD SEP PY 2009 VL 6 IS 9 BP 569 EP 579 DI 10.1038/nrcardio.2009.119 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 485UJ UT WOS:000269150000007 PM 19621013 ER PT J AU Janne, PA Gray, N Settleman, J AF Jaenne, Pasi A. Gray, Nathanael Settleman, Jeff TI Factors underlying sensitivity of cancers to small-molecule kinase inhibitors SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; CHRONIC MYELOID-LEUKEMIA; PHASE-II TRIAL; GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOMONOCYTIC LEUKEMIA; METASTATIC BREAST-CANCER; EML4-ALK FUSION GENE; TYROSINE KINASE; ACTIVATING MUTATIONS AB Selective small-molecule kinase inhibitors have emerged over the past decade as an important class of anti-cancer agents, and have demonstrated impressive clinical efficacy in several different diseases, including relatively common malignancies such as breast and lung cancer. However, clinical benefit is typically limited to a fraction of treated patients. Genomic features of individual tumours contribute significantly to such clinical responses, and these seem to vary tremendously across patients. Additional factors, including pharmacogenomics, the tumour microenvironment and rapidly acquired drug resistance, also contribute to the clinical sensitivity of various cancers, and should be considered and applied in the development and use of new kinase inhibitors. C1 [Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Settleman, Jeff] Harvard Univ, Sch Med, Charlestown, MA USA. [Jaenne, Pasi A.; Gray, Nathanael] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jaenne, Pasi A.; Gray, Nathanael] Harvard Univ, Sch Med, Boston, MA USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. EM Settleman@helix.mgh.harvard.edu RI han, chao/B-6245-2011 NR 140 TC 190 Z9 193 U1 0 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2009 VL 8 IS 9 BP 709 EP 723 DI 10.1038/nrd2871 PG 15 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 489IG UT WOS:000269413100017 PM 19629074 ER PT J AU Meeran, SM Katiyar, N Singh, T Katiyar, SK AF Meeran, Syed M. Katiyar, Nandan Singh, Tripti Katiyar, Santosh K. TI Loss of Endogenous Interleukin-12 Activates Survival Signals in Ultraviolet-Exposed Mouse Skin and Skin Tumors SO NEOPLASIA LA English DT Article ID NF-KAPPA-B; SKH-1 HAIRLESS MICE; GROWTH IN-VIVO; INDUCED APOPTOSIS; HUMAN CANCER; PHOTOCARCINOGENESIS; PROANTHOCYANIDINS; INHIBITION; EXPRESSION; PATHWAY AB Interleukin-12 (IL-12)-deficiency promotes photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. Here, we report that long-term exposure to ultraviolet (UV) radiation resulted in enhancement of the levels of cell survival kinases, such as phosphatidylinositol 3-kinase (PI3K), Akt (Ser(473)), p-ERK1/2, and p-p38 in the skin of IL-12p40 knockout (IL-12 KO) mice compared with the skin of wild-type mice. UV-induced activation of nuclear factor-kappa B (NF-kappa B)/p65 in the skin of IL-12 KO mice was also more prominent. The levels of NF-kappa B-targeted proteins, such as proliferating cell nuclear antigen (PCNA), cyclooxygenase-2, cyclin D1, and inducible nitric oxide synthase, were higher in the UV-exposed skin of IL-12 KO mice than the UV-exposed skin of wild types. In short-term UV irradiation experiments, subcutaneous treatment of IL-12 KO mice with recombinant IL-12 (rIL-12) or topical treatment with oridonin, an inhibitor of NF-kappa B,resulted in the inhibition of UV-induced increases in the levels of PCNA, cyclin D1, and NF-kappa B compared with non-rIL-12- or non-oridonin-treated IL-12 KO mice. UV-induced skin tumors of IL-12 KO mice had higher levels of PI3K, p-Akt (Ser(473)), p-ERK1/2, p-p38, NF-kappa B, and PCNA and fewer apoptotic cells than skin tumors of wild types. Together, these data suggest that the loss of endogenous IL-12 activates survival signals in UV-exposed skin and that may lead to the enhanced photocarcinogenesis in mice. C1 [Meeran, Syed M.; Katiyar, Nandan; Singh, Tripti; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Center for Complementary and AlternativeMedicine/NIH [1 RO1 AT002536]; Veterans Administration Merit Review Award FX This work was supported by grants from the National Center for Complementary and AlternativeMedicine/NIH (1 RO1 AT002536; S.K.K.) and the Veterans Administration Merit Review Award (S.K.K.). No conflict of interest. NR 34 TC 10 Z9 13 U1 0 U2 0 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD SEP PY 2009 VL 11 IS 9 BP 846 EP 855 DI 10.1593/neo.09528 PG 10 WC Oncology SC Oncology GA 497EJ UT WOS:000270038200003 PM 19724678 ER PT J AU Kawakami, T Inagi, R Takano, H Sato, S Ingelfinger, JR Fujita, T Nangaku, M AF Kawakami, Takahisa Inagi, Reiko Takano, Hideki Sato, Shigeru Ingelfinger, Julie R. Fujita, Toshiro Nangaku, Masaomi TI Endoplasmic reticulum stress induces autophagy in renal proximal tubular cells SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE autophagy; ERK; ER stress; LC3 ID CELLULAR AUTOPHAGY; ER STRESS; BREFELDIN-A; HEMODYNAMIC STRESS; SECRETORY PROTEINS; REGULATED PROTEIN; OXIDATIVE STRESS; MAMMALIAN-CELLS; KIDNEY-CORTEX; RAT-KIDNEY AB Methods. Immortalized rat proximal tubular cells were exposed to the classic ER stress inducers tunicamycin or brefeldin A. Autophagy was detected mainly by immunoblot analysis of LC3, a widely used marker of autophagy, and also by immunofluorescent cytochemistry of LC3 and electron microscopy. Biological significance of the phenomenon was studied using bafilomycin A1, an inhibitor of autophagosome degradation. Signal transduction pathways following ER stress were also investigated using inhibitors of the MAPK pathway. Results. Both ER stress inducers significantly increased LC3-II as a marker of autophagy in immunoblot analysis. Immunocytochemistry of LC3 and electron microscopy also showed activation of autophagy by ER stress. Inhibition by bafilomycin A1 showed that autophagy following ER stress fulfilled its intrinsic function, namely degradation of cytoplasmic components. Further, use of the MEK 1/2 inhibitor U0126, which inhibits ER stress-induced autophagy induction and ERK activation, showed that ERK, a MAPK family member, was necessary to the induction of autophagy. Conclusions. For the first time, we demonstrate the induction of autophagy following ER stress in renal tubules, and clarify its mechanism. These findings serve as the foundation for further investigation into autophagy in renal diseases. C1 [Kawakami, Takahisa; Inagi, Reiko; Takano, Hideki; Fujita, Toshiro; Nangaku, Masaomi] Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Tokyo 113, Japan. [Sato, Shigeru] Nippon Med Sch, Cent Inst Elect Microscop Res, Tokyo 113, Japan. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. RP Nangaku, M (reprint author), Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Tokyo 113, Japan. EM mnangaku-tky@umin.ac.jp FU Japan Society for the Promotion of Science [19390228, 19590939] FX This work was supported by a Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science (19390228) to M. N. and (19590939) to R. I. We are grateful to Noboru Mizushima (Tokyo Medical and Dental University, Japan) for his comprehensive and detailed advice on the detection of autophagy. NR 58 TC 57 Z9 62 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD SEP PY 2009 VL 24 IS 9 BP 2665 EP 2672 DI 10.1093/ndt/gfp215 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 486PD UT WOS:000269208500010 PM 19454529 ER PT J AU Philipson, O Hammarstrom, P Nilsson, KPR Portelius, E Olofsson, T Ingelsson, M Hyman, BT Blennow, K Lannfelt, L Kalimo, H Nilsson, LNG AF Philipson, Ola Hammarstrom, Per Nilsson, K. Peter R. Portelius, Erik Olofsson, Tommie Ingelsson, Martin Hyman, Bradley T. Blennow, Kaj Lannfelt, Lars Kalimo, Hannu Nilsson, Lars N. G. TI A highly insoluble state of A beta similar to that of Alzheimer's disease brain is found in Arctic APP transgenic mice SO NEUROBIOLOGY OF AGING LA English DT Article DE Immunotherapy; Solubility; ABeta-peptide; Alzheimer's disease; Amyloid beta; Transgenic ID AMYLOID PRECURSOR PROTEIN; SENSITIVE OPTICAL PROBES; MOUSE MODEL; SENILE PLAQUES; CONJUGATED POLYELECTROLYTES; CEREBROSPINAL-FLUID; MASS-SPECTROMETRY; MEMORY DEFICITS; CORE PROTEIN; DEPOSITION AB Amyloid-beta (A beta) is a major drug target in Alzheimer's disease. Here, we demonstrate that deposited A beta is SDS insoluble in tgAPP-ArcSwe, a transgenic mouse model harboring the Arctic (E693G) and Swedish (KM670/671NL) APP mutations. Formic acid was needed to extract the majority of deposited A beta in both tgAPP-ArcSwe and Alzheimer's disease brain, but not in a commonly used type of mouse model with the Swedish mutation alone. Interestingly, the insoluble state of Arctic A beta was determined early on and did not gradually evolve with time. In tgAPP-AreSwe, A beta plaques displayed a patchy morphology with bundles of A beta fibrils, whereas amyloid cores in tgAPP-Swe were circular with radiating fibrils. Amyloid was more densely stacked in tgAPP-ArcSwe, as demonstrated with a conformation sensitive probe. A reduced increase in plasma A beta was observed following acute administration of an A beta antibody in tgAPP-ArcSwe, results that might imply reduced brain to plasma A beta efflux. TgAPP-ArcSwe, with its insoluble state of deposited A beta, could serve as a complementary model to better predict the outcome of clinical trials. (C) 2007 Elsevier Inc. All fights reserved. C1 [Philipson, Ola; Ingelsson, Martin; Lannfelt, Lars; Nilsson, Lars N. G.] Uppsala Univ, Dept Publ Hlth & Caring Sci, SE-75185 Uppsala, Sweden. [Hammarstrom, Per; Nilsson, K. Peter R.] Linkoping Univ, Dept Chem, IFM, SE-58183 Linkoping, Sweden. [Nilsson, K. Peter R.] Univ Spital Zurich, Inst Neuropathol, CH-809 Zurich, Switzerland. [Portelius, Erik; Blennow, Kaj] Sahlgrens Univ Hosp, Dept Ncurosci & Physiol, SE-43180 Molndal, Sweden. [Olofsson, Tommie; Kalimo, Hannu] Uppsala Univ, Univ Hosp, Dept Genet & Pathol, SE-75185 Uppsala, Sweden. [Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Kalimo, Hannu] Univ Helsinki, Univ Helsinki Hosp, Dept Pathol, FI-00014 Helsinki, Finland. RP Nilsson, LNG (reprint author), Rudbeck Lab, Dag Hammarskjolds Vag 20, SE-75185 Uppsala, Sweden. EM lars.nilsson@pubcare.uu.se FU Uppsala University; Landstinget i Uppsala lan; Swedish Brain Fund; Bertil Hillstens Forskningsstiftelse; Alzheimerfonden; Sahlgrenska University Hospital; Gamla Tjanarinnor; Gun och Bertil Stolmes Stiftelse; Magnus Bergvall; Ahlonsstiftelsen; Lars Hierta; Lundstroms Minne; Frimurarstiftelsen; Svenska Lakarsallskapet; Swedish Research Council [2006-2822, 2006-2818, 2006-6326, 2006-3464, 2004-2696]; Knut and Alice Wallenberg foundation; Swedish foundation for strategic research; Sven and Ebba-Christina Hagbergs stiftelse FX This work was funded by grants from Uppsala University, Landstinget i Uppsala lan, The Swedish Brain Fund, Bertil Hillstens Forskningsstiftelse, Alzheimerfonden (L.L.), the Sahlgrenska University Hospital (K.B.), Gamla Tjanarinnor, Gun och Bertil Stolmes Stiftelse (L.N., O.P.), Magnus Bergvall, Ahlonsstiftelsen, Lars Hierta, Lundstroms Minne, Frimurarstiftelsen, Svenska Lakarsallskapet (L.N.), the Swedish Research Council [(#2006-2822) L.L., (#2006-2818) L.N., (#2006-6326; #2006-3464) M.I., (#2004-2696) P.H.], Knut and Alice Wallenberg foundation, the Swedish foundation for strategic research (P.H., K.P.R.N.) and Sven and Ebba-Christina Hagbergs stiftelse (P.H). AP antibodies are kindly provided by Dr J. Ndslund and Dr P. Mehta. The Uppsala University Transgenic Facility (UUTF) is greatly acknowledged for their help in developing the APP transgenic models used in this study and Paul O'Callaghan for linguistic advice. NR 53 TC 40 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2009 VL 30 IS 9 BP 1393 EP 1405 DI 10.1016/j.neurobiolaging.2007.11.022 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 481CA UT WOS:000268783200005 PM 18192084 ER PT J AU Holden, KF Lindquist, K Tylavsky, FA Rosano, C Harris, TB Yaffe, K AF Holden, Karen F. Lindquist, Karla Tylavsky, Frances A. Rosano, Caterina Harris, Tamara B. Yaffe, Kristine CA Hlth ABC Study TI Serum leptin level and cognition in the elderly: Findings from the Health ABC Study SO NEUROBIOLOGY OF AGING LA English DT Article DE Leptin; Cognition; Learning; Memory; Elderly; Aging; Dementia; Alzheimer's disease; Obesity; Hyperleptinemia; Leptin resistance; Metabolic syndrome ID HIPPOCAMPAL SYNAPTIC PLASTICITY; MICE OVEREXPRESSING LEPTIN; LONG-TERM POTENTIATION; BLOOD-BRAIN-BARRIER; INSULIN SENSITIVITY; GLUCOSE-METABOLISM; OLDER WOMEN; RESISTANCE; OBESITY; RATS AB Leptin is a peptide hormone secreted by adipocytes. It has been shown to modulate production and clearance of amyloid beta (A beta) in rodent models. We sought to determine if serum leptin was associated with cognitive decline in the elderly. We studied 2871 well-functioning elders, aged 70-79, who were enrolled in a prospective study. Serum leptin concentrations were measured at baseline and analyzed by mean +/- 1S.D. Clinically significantly cognitive decline over 4 years was defined as >= 5-point drop on the Modified Mini Mental State Exam (3MS). Compared to those in the lower leptin groups, elders in the high leptin group had less cognitive decline, 20.5% versus 24.7% (OR=0.79; 95% CI 0.61-1.02, p = 0.07). After adjustment for demographic and clinical variables, including body mass index and total percent body fat, those in the high leptin group had significantly less likelihood of cognitive decline, OR = 0.66 (95% CI 0.48-0.91). We conclude that in elderly individuals, higher serum leptin appears to protect against cognitive decline, independent of comorbidites and body fat. (C) 2007 Elsevier Inc. All rights reserved. C1 [Holden, Karen F.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Lindquist, Karla] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tylavsky, Frances A.] Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. [Rosano, Caterina] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Holden, KF (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94143 USA. EM karenholden@mac.com OI Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU Paul Beeson Faculty Scholar in Aging Program; NIH [R01 AG021918-01]; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-21] FX Dr. Yaffe is supported by the Paul Beeson Faculty Scholar in Aging Program and NIH grant R01 AG021918-01. This research was supported in part by the Intramural Research program of the NIA, National Institute of Aging, as well as NIA contracts N01-AG-6-2101, N01-AG-6-2103 and N01-AG-6-21. NR 58 TC 88 Z9 90 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2009 VL 30 IS 9 BP 1483 EP 1489 DI 10.1016/j.neurobiolaging.2007.11.024 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 481CA UT WOS:000268783200014 PM 18358569 ER PT J AU Menalled, L El-Khodor, BF Patry, M Suarez-Farinas, M Orenstein, SJ Zahasky, B Leahy, C Wheeler, V Yang, XW MacDonald, M Morton, AJ Bates, G Leeds, J Park, L Howland, D Signer, E Tobin, A Brunner, D AF Menalled, Liliana El-Khodor, Bassem F. Patry, Monica Suarez-Farinas, Mayte orenstein, Samantha J. Zahasky, Benjamin Leahy, Christina Wheeler, Vanessa Yang, X. William MacDonald, Marcy Morton, A. Jennifer Bates, Gill Leeds, Janet Park, Larry Howland, David Signer, Ethan Tobin, Allan Brunner, Daniela TI Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models SO NEUROBIOLOGY OF DISEASE LA English DT Article ID ENVIRONMENTAL ENRICHMENT; MUTANT HUNTINGTIN; CAG REPEAT; TRINUCLEOTIDE REPEAT; PREPULSE INHIBITION; STARTLE RESPONSE; MOTOR DEFICITS; MICE; ABNORMALITIES; HD AB Huntington's disease (HD) is one of the few neurodegenerative diseases with a known genetic cause, knowledge that has enabled the creation of animal models using genetic manipulations that aim to recapitulate HD pathology. The study of behavioral and neuropathological phenotypes of these HD models, however, has been plagued by inconsistent results across laboratories stemming from the lack of standardized husbandry and testing conditions, in addition to the intrinsic differences between the models. We have compared different HD models using standardized conditions to identify the most robust phenotypic differences, best suited for preclinical therapeutic efficacy studies. With a battery of tests of sensory-motor function, such as the open field and prepulse inhibition tests, we replicate previous results showing a strong and progressive behavioral deficit in the R6/2 line with an average of 129 CAG repeats in a mixed CBA/J and C57BL/6J background. We present the first behavioral characterization of a new model, an R6/2 line with an average of 248 CAG repeats in a pure C57BL/6J background, which also showed a progressive and robust phenotype. The BACHD in a FVB/N background showed robust and progressive behavioral phenotype, while the YAC128 full-length model on either an FVB/N or a C57BL/6J background generally showed milder deficits. Finally, the Hdh(Q111) knock-in mouse on a CD1 background showed very mild deficits. This first extensive standardized cross-characterization of several HD animal models under standardized conditions highlights several behavioral outcomes, such as hypoactivity, amenable to standardized preclinical therapeutic drug screening. (C) 2009 Elsevier Inc. All rights reserved. C1 [Menalled, Liliana; El-Khodor, Bassem F.; Patry, Monica; orenstein, Samantha J.; Zahasky, Benjamin; Leahy, Christina; Brunner, Daniela] PsychoGenics Inc, Tarrytown, NY 10591 USA. [Suarez-Farinas, Mayte] Rockefeller Univ Hosp, New York, NY 10065 USA. [Wheeler, Vanessa; MacDonald, Marcy] Massachusetts Gen Hosp, Mol Neurogenet Lab, Charlestown, MA 02129 USA. [Yang, X. William] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobehav Genet, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Yang, X. William] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Yang, X. William] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Morton, A. Jennifer] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England. [Bates, Gill] Kings Coll London, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England. [Leeds, Janet; Park, Larry; Howland, David; Signer, Ethan; Tobin, Allan] CHDI Fdn, New York, NY 10001 USA. [Brunner, Daniela] Columbia Univ, Dept Psychiat, New York, NY 10032 USA. RP Brunner, D (reprint author), PsychoGenics Inc, 765 Old Saw Mill River Rd, Tarrytown, NY 10593 USA. EM dani.brunner@psychogenics.com RI Bates, Gillian/E-1146-2012; Suarez-Farinas, Mayte/I-3558-2012 OI Bates, Gillian/0000-0002-4041-6305; Suarez-Farinas, Mayte/0000-0001-8712-3553 FU NINDS/NIH [R01 NS049501]; CHDI; HDF FX We are grateful to Drs. Michael Hayden and Blair Leavitt for YAC728 mice, Dr. Jeff Schneider for the statistical support, Dr. Marie Francoise Chesselet, for numerous discussions and suggestions. Our thanks to Jennifer Goodman, Albert Jimenez, Jennie Murphy, Natalie Morgan, Morgen Peck, Jennifer Galarza, Sidra Khalid Melinda Ruiz and Meredith Taylor for help with the breeding, behavioral experiments and operations. Dr. X. William Yang was supported by an NINDS/NIH (R01 NS049501) grant and grants from CHDI and HDF. NR 45 TC 140 Z9 141 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD SEP PY 2009 VL 35 IS 3 BP 319 EP 336 DI 10.1016/j.nbd.2009.05.007 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 486ET UT WOS:000269179400001 PM 19464370 ER PT J AU Astradsson, A Jenkins, BG Choi, JK Hallett, PJ Levesque, MA McDowell, JS Brownell, AL Spealman, RD Isacson, O AF Astradsson, Arnar Jenkins, Bruce G. Choi, Ji-Kyung Hallett, Penelope J. Levesque, Michele A. McDowell, Jack S. Brownell, Anna-Liisa Spealman, Roger D. Isacson, Ole TI The blood-brain barrier is intact after levodopa-induced dyskinesias in parkinsonian primates-Evidence from in vivo neuroimaging studies SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Levodopa; Dyskinesia; Primates; Blood-brain barrier; Imaging; Gadolinium-DTPA ID MULTIPLE-SCLEROSIS; DISEASE; PERMEABILITY; MODEL; MRI; SUBTYPES AB It has been suggested, based on rodent studies, that levodopa (L-dopa) induced dyskinesia is associated with a disrupted blood-brain barrier (BBB). We have investigated BBB integrity with in vivo neuroimaging techniques in six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned primates exhibiting dopa-induced dyskinesia. Magnetic resonance imaging (MRI) performed before and after injection of Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) revealed an intact BBB in the basal ganglia showing that L-dopa-induced dyskinesia is not associated with a disrupted BBB in this model. (C) 2009 Elsevier Inc. All rights reserved. C1 [Astradsson, Arnar; Jenkins, Bruce G.; Hallett, Penelope J.; Levesque, Michele A.; McDowell, Jack S.; Brownell, Anna-Liisa; Spealman, Roger D.; Isacson, Ole] Harvard Univ, Belmont, MA 02478 USA. [Astradsson, Arnar; Jenkins, Bruce G.; Hallett, Penelope J.; Levesque, Michele A.; McDowell, Jack S.; Brownell, Anna-Liisa; Spealman, Roger D.; Isacson, Ole] McLean Hosp, NINDS Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02178 USA. [Jenkins, Bruce G.; Choi, Ji-Kyung] Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Brownell, Anna-Liisa] Massachusetts Gen Hosp, MGH Positron Emiss Tomog Ctr, Boston, MA 02114 USA. [Astradsson, Arnar; Hallett, Penelope J.; Levesque, Michele A.; McDowell, Jack S.; Spealman, Roger D.; Isacson, Ole] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. RP Isacson, O (reprint author), Harvard Univ, Sch Med, McLean Hosp, Ctr Neuroregenerat Res, MRC 130,115 Mill St, Belmont, MA 02478 USA. EM isacson@hms.harvard.edu OI Hallett, Penelope/0000-0002-8858-9096 FU US National Institutes of Health [P50 NS39793, RR00168]; Michael Stern Foundation; Consolidated Anti-Aging Foundation; Orchard Foundation FX This work was supported by the US National Institutes of Health NINDS Udall Parkinson's Disease Research Center of Excellence (P50 NS39793), The Michael Stern Foundation, the Consolidated Anti-Aging Foundation, the Orchard Foundation, and an NIH base grant to NEPRC (RR00168). The authors declare no financial conflict of interest. We thank Angela Carville and Shannon Luboyeski for veterinary assistance. NR 25 TC 17 Z9 17 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD SEP PY 2009 VL 35 IS 3 BP 348 EP 351 DI 10.1016/j.nbd.2009.05.018 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 486ET UT WOS:000269179400003 PM 19501164 ER PT J AU Labus, JS Naliboff, BD Berman, SM Suyenobu, B Vianna, EP Tillisch, K Mayer, EA AF Labus, Jennifer S. Naliboff, Bruce D. Berman, Steve M. Suyenobu, Brandall Vianna, Eduardo P. Tillisch, Kirsten Mayer, Emeran A. TI Brain networks underlying perceptual habituation to repeated aversive visceral stimuli in patients with irritable bowel syndrome SO NEUROIMAGE LA English DT Article ID PARTIAL LEAST-SQUARES; EFFECTIVE CONNECTIVITY; ATTENTIONAL NETWORKS; PREFRONTAL CORTEX; NEURAL MECHANISMS; FEARFUL FACES; CHRONIC PAIN; ANXIETY; AWARENESS; CONFLICT AB Patients with irritable bowel syndrome (IBS) show decreased discomfort and pain thresholds to visceral stimuli, as well hypervigilance to gastrointestinal sensations, symptoms, and the context in which these visceral sensations and symptoms occur. Previous research demonstrated normalization of visceral hypersensitivity following repeated exposure to experimental rectal stimuli over a 12-month period that was associated with reduction in cortical regions functionally associated with attention and arousal. Building upon these functional analyses, multivariate functional and effective connectivity analyses were applied to [(15)O] water positron emission tomography (PET) data from 12 IBS patients (male = 4) Participating in a PET Study before and after 4 visceral sensory testing sessions involving rectal balloon distensions over a 1-year period. First, behavioral partial least squares was applied to test for networks related to reduced subjective ratings observed following repeated application of an aversive rectal stimulus. Next, path analysis within a structural equation modeling framework tested the hypothesis that perceptual habituation to the repeated visceral Stimuli resulted in part from the reduced connectivity within a selective attention to threat network over time. Two independent, perception-related networks comprised of interoceptive, attentional and arousal regions were engaged differentially during expectation and distension. In addition, changes in the effective connectivity of an attentional network as well as modulatory amygdala influence suggested that perceptual habituation associated with repeated stimulus delivery results both in an increase in top-down modulation of attentional circuits, as well as in a reduction of amygdala-related interference with attentional mechanisms. (C) 2009 Elsevier Inc. All rights reserved. C1 [Labus, Jennifer S.; Naliboff, Bruce D.; Berman, Steve M.; Suyenobu, Brandall; Vianna, Eduardo P.; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. [Berman, Steve M.; Suyenobu, Brandall; Vianna, Eduardo P.; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Labus, Jennifer S.; Naliboff, Bruce D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Labus, Jennifer S.; Berman, Steve M.; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Naliboff, Bruce D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Labus, JS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Peter V Ueberroth Bldg,Rm 2338C2,10945 LeConte Av, Los Angeles, CA 90095 USA. EM jlabus@ucla.edu FU VA PET Center FX We would like to acknowledge the invaluable support by the VA PET Center under the direction of Dr. Mark Mandelkern. NR 67 TC 37 Z9 39 U1 3 U2 7 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 SEP PY 2009 VL 47 IS 3 BP 952 EP 960 DI 10.1016/j.neuroimage.2009.05.078 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 482YI UT WOS:000268926200021 PM 19501173 ER PT J AU Evans, KC Dougherty, DD Schmid, AM Scannell, E McCallister, A Benson, H Dusek, JA Lazar, SW AF Evans, Karleyton C. Dougherty, Darin D. Schmid, Annette M. Scannell, Elizabeth McCallister, Adrienne Benson, Herbert Dusek, Jeffery A. Lazar, Sara W. TI Modulation of spontaneous breathing via limbic/paralimbic-bulbar circuitry: An event-related fMRI study SO NEUROIMAGE LA English DT Review DE fMRI; Respiration; Limbic; Brainstem ID CENTRAL HYPOVENTILATION SYNDROME; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; OLD-WORLD MONKEY; HUMAN BRAIN; INSULAR CORTEX; HEART-RATE; RESPIRATORY CORRELATIONS; VOLITIONAL INSPIRATION; HEMODYNAMIC-RESPONSE AB It is well established that pacemaker neurons in the brainstem provide automatic control of breathing for metabolic homeostasis and Survival. During waking spontaneous breathing, cognitive and emotional demands can modulate thee intrinsic brainstem respiratory rhythm. However the neural circuitry mediating this modulation is unknown. Studies of supra-pontine influences oil the control of breathing have implicated limbic/paralimbic-bulbar Circuitry, but these studies have been limited to either invasive surgical electrophysiological methods or neuroimaging during Substantial respiratory provocation. Here we probed the limbic/paralimbic-bulbar Circuitry for respiratory-related neural activity during unlabored spontaneous breathing at rest as well as during a challenging cognitive task (sustained random number generation). Functional magnetic resonance imaging (fMRI) with simultaneous physiological monitoring (heart rate, respiratory rate, tidal volume, end-tidal CO(2)) Was acquired in 14 healthy Subjects during each condition. The cognitive task produced expected increases in breathing rate, while end-tidal CO(2) and heart rate (lid not significantly differ between conditions. The respiratory cycle served as the input function for breath-by-breath, event-related, voxel-wise, random-effects image analyses in SPM5. Main effects analyses (cognitive task + rest) demonstrated the first evidence of coordinated neural activity associated with spontaneous breathing within the medulla. pons, midbrain, amygdala, anterior cingulate and anterior insular cortices. Between-condition paired t-tests (cognitive task>rest) demonstrated modulation Within this network localized to the dorsal anterior cingulate and pontine raphe magnus nucleus. We propose that the identified limbic/paralimbic-bulbar circuitry plays a significant role in cognitive and emotional modulation Of spontaneous breathing. (C) 2009 Elsevier Inc. All rights reserved. C1 [Evans, Karleyton C.; Dougherty, Darin D.; Scannell, Elizabeth; McCallister, Adrienne; Lazar, Sara W.] Massachusetts Gen Hosp E, Div Neurotherapeut, Dept Psychiat, Charlestown, MA 02129 USA. [Schmid, Annette M.] Percept Informat Inc, Waltham, MA USA. [Benson, Herbert; Dusek, Jeffery A.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA USA. RP Evans, KC (reprint author), Massachusetts Gen Hosp E, Div Neurotherapeut, Dept Psychiat, 13th St,Bldg 149,Suite 2625, Charlestown, MA 02129 USA. EM kcevans@partners.org RI Lazar, Sara/G-3809-2012; OI Lazar, Sara/0000-0003-1126-8363; Dusek, Jeffery/0000-0001-9581-0564 FU NIBIB [T-32 EB001632-03]; NCCAM [R21 AT003425-01A2S1, K01AT00694-01, IR21AT003673-01]; Massachusetts General Hospital Executive Committee on Research; [H75/CCH119124]; [H75/CCH123424]; [5R01DP000339] FX We wish to acknowledge Pandy Buckner, Robert Banzett and Kenneth Kwong for their thoughtful discussion and comments. This work was supported in part by grants H75/CCH119124, H75/CCH123424 and 5R01DP000339. Dr. Evans received Support from grants T-32 EB001632-03 (NIBIB), R21 AT003425-01A2S1 (NCCAM) and a Faculty Development Award from the Massachusetts General Hospital Executive Committee on Research. Dr. Lazar received support from grants K01AT00694-01 (NCCAM) and IR21AT003673-01 (NCCAM). NR 122 TC 28 Z9 29 U1 3 U2 15 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 SEP PY 2009 VL 47 IS 3 BP 961 EP 971 DI 10.1016/j.neuroimage.2009.05.025 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 482YI UT WOS:000268926200022 PM 19450692 ER PT J AU Napadow, V Dhond, RP Kim, J LaCount, L Vangel, M Harris, RE Kettner, N Park, K AF Napadow, Vitaly Dhond, Rupali P. Kim, Jieun LaCount, Lauren Vangel, Mark Harris, Richard E. Kettner, Norman Park, Kyungmo TI Brain encoding of acupuncture sensation - Coupling on-line rating with fMRI SO NEUROIMAGE LA English DT Article ID PREFRONTAL CORTICAL PROJECTIONS; COGNITIVE MODULATION; SHAM ACUPUNCTURE; MACAQUE MONKEYS; FRONTAL-CORTEX; BODY AWARENESS; CHRONIC PAIN; BACK-PAIN; STIMULATION; DEFAULT AB Acupuncture-induced sensations have historically been associated with clinical efficacy. These sensations are atypical, arising from sub-dermal receptors, and their neural encoding is not well known. In this fMRI study, subjects were stimulated at acupoint PC-6, while rating sensation with a custom-built, MR-compatible potentiometer. Separate runs included real (ACUP) and sham (SHAM) acupuncture, the latter characterized by non-insertive, Cutaneous stimulation. FMRI data analysis Was guided by the on-line rating timeseries, thereby localizing brain correlates of acupuncture sensation. Sensation ratings correlated with stimulation more (p<0.001) for SHAM (r=0.63) than for ACUP (r=0.32), ACUP induced stronger and more varied sensations with significant persistence into no-stimulation blocks, leading to more run-time spent rating low and moderate sensations compared to SHAM. ACUP sensation correlated with activation in regions associated with sensorimotor (SII, insula) and cognitive (dorsomedial prefrontal cortex (dmPFC)) processing, and deactivation in default-mode network (DMN) regions (posterior cingulate, precuneus). Compared to SHAM, ACUP yielded greater activity in both anterior and posterior dmPFC and dmPFC. fit contrast, SHAM produced greater activation in sensorimotor (SI, SII, insula) and greater deactivation in DMN regions. Thus, brain encoding of ACUP sensation (more persistent and varied, leading to increased cognitive load) demonstrated greater activity in both cognitive/evaluative (posterior dmPFC) and emotional/interoceptive (anterior dmPFC) cortical regions. Increased cognitive load and dmPFC activity may be a salient component of acupuncture analgesia - sensations focus attention and accentuate bodily awareness, contributing to enhanced top-down modulation of any nociceptive afference and central pain networks. Hence, acupuncture may function as a somatosensory-guided mind-body therapy. (C) 2009 Elsevier Inc. All rights reserved. C1 [Napadow, Vitaly; Dhond, Rupali P.; Kim, Jieun; LaCount, Lauren; Vangel, Mark; Park, Kyungmo] Massachusetts Gen Hosp, HMS MIT, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Napadow, Vitaly; Dhond, Rupali P.; Kettner, Norman] Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. [Kim, Jieun; Park, Kyungmo] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. [Vangel, Mark] MGH GCRC Biomed Imaging Core, Charlestown, MA USA. [Harris, Richard E.] Univ Michigan, Dept Anesthesiol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA. RP Napadow, V (reprint author), Martinos Ctr Biomed Imaging, 149 13th St,2301, Charlestown, MA 02129 USA. RI Harris, Richard/F-1307-2011 FU NIH [K01-AT002166, R01-AT004714, P01-AT002048, K01-AT004481, K01-AT01111, F05-AT003770]; NCRR [P41-RR14075]; GCRC [M01-RR01066]; Institute of Information Technology Advancement, Korea [IITA-2008-(C1090-0801-0002)]; Department of Army [W81XWH-07-2-0050]; Dana Foundation Award [K24-AT004095] FX We Would like to thank the National Center for Complementary and Alternative Medicine, NIH for funding Support: K01-AT002166, R01-AT004714 (Napadow), P01-AT002048 (Rosen), K01-AT004481 (Dhond), K01-AT01111 (Harris) and F05-AT003770 (Park). We also acknowledge the NCRR (P41-RR14075, GCRC M01-RR01066), the Mental Illness and Neuroscience Discovery (MIND) Institute. Dr. Park was also supported by the Institute of Information Technology Advancement, Korea IITA-2008-(C1090-0801-0002). Dr. Harris was also Supported by Department of Army grant DAMD-Award Number W81XWH-07-2-0050, and Dana Foundation Award ill Brain and Immuno-imaging. We would also like to thank Bruce Rosen and Ted Kaptchuk (K24-AT004095) for helpful comments oil the interpretation of our data. The content is solely the responsibility of the authors and does not necessarily represent the official views of our funding agencies. NR 50 TC 52 Z9 61 U1 0 U2 12 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 SEP PY 2009 VL 47 IS 3 BP 1055 EP 1065 DI 10.1016/j.neuroimage.2009.05.079 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 482YI UT WOS:000268926200033 PM 19500677 ER PT J AU Kong, J Kaptchuk, TJ Polich, G Kirsch, I Vangel, M Zyloney, C Rosen, B Gollub, RL AF Kong, Jian Kaptchuk, Ted J. Polich, Ginger Kirsch, Irving Vangel, Mark Zyloney, Carolyn Rosen, Bruce Gollub, Randy L. TI An fMRI study on the interaction and dissociation between expectation of pain relief and acupuncture treatment SO NEUROIMAGE LA English DT Article DE Acupuncture; Acupuncture analgesia; Placebo; Placebo analgesia; Expectancy; Expectancy manipulation; Conditioning; Pain; Sham acupuncture needle ID RANDOMIZED CONTROLLED-TRIAL; LOW-BACK-PAIN; MEDIAL PREFRONTAL CORTEX; PLACEBO ANALGESIA; ACUPOINT STIMULATION; NEURAL MECHANISMS; OPIOID ACTIVITY; BRAIN ACTIVITY; RATIO SCALES; RESPONSES AB It is well established that expectation can significantly modulate pain perception, In this Study, we combined an expectancy manipulation model and fMRI to investigate how expectation can modulate acupuncture treatment. Forty-eight subjects completed the study. The analysis on two verum acupuncture groups with different expectancy levels indicates that expectancy can significantly influence acupuncture analgesia for experimental pain. Conditioning positive expectation can amplify acupuncture analgesia as detected by subjective pain sensory rating changes and objective fMRI signal changes in response to calibrated noxious stimuli. Diminished positive expectation appeared to inhibit acupuncture analgesia. This modulation effect is spatially specific, inducing analgesia exclusively in regions of the body where expectation is focused. Thus, expectation should be used as an important covariate in future studies evaluating acupuncture efficacy. In addition, we also observed dissociation between subjective reported analgesia and objective fMRI signal changes to calibrated pain in the analysis across all four groups. We hypothesize that as a peripheral-central modulation, acupuncture needle stimulation may inhibit incoming noxious Stimuli; while as a top-down modulation, expectancy (placebo) may work through the emotional circuit. (C) 2009 Elsevier Inc. All rights reserved. C1 [Kong, Jian; Polich, Ginger; Zyloney, Carolyn; Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Kong, Jian; Vangel, Mark; Rosen, Bruce; Gollub, Randy L.] Athinoula A Martinos Ctr Biomed Imaging, MGH MIT HMS, Charlestown, MA USA. [Kaptchuk, Ted J.] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA USA. [Kirsch, Irving] Univ Hull, Kingston Upon Hull HU6 7RX, N Humberside, England. [Vangel, Mark; Gollub, Randy L.] MGH CRC Biomed Imaging Core, Charlestown, MA USA. RP Kong, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St,Suite 2661, Charlestown, MA 02129 USA. EM kongj@nmr.mgh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044 FU National Center for Complimentary and Alternative Medicine (NCCAM) [R21AT00949, KO1AT003883, K24AT004095, M01-RR-01066, UL1 RR025758-01]; National Center for Research Resources (NCRR) [P41RR14075] FX This work was Supported by PO1-AT002048 to Bruce Rosen from National Center for Complimentary and Alternative Medicine (NCCAM). R21AT00949 to Randy Gollub from NCCAM, KO1AT003883 to Jian Kong from NCCAM, K24AT004095 to Ted Kaptchuk from NCCAM, M01-RR-01066 and UL1 RR025758-01 for Clinical Research Center Biomedical Imaging Core from National Center for Research Resources (NCRR), P41RR14075 for Center for Functional Neuroimaging Technologies from NCRR and the MIND Institute. NR 70 TC 71 Z9 81 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 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2009 VL 47 IS 3 BP 1066 EP 1076 DI 10.1016/j.neuroimage.2009.05.087 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 482YI UT WOS:000268926200034 PM 19501656 ER PT J AU Harris, RE Zubieta, JK Scott, DJ Napadow, V Gracely, RH Clauw, DJ AF Harris, Richard E. Zubieta, Jon-Kar Scott, David J. Napadow, Vitaly Gracely, Richard H. Clauw, Daniel J. TI Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs) SO NEUROIMAGE LA English DT Article DE Acupuncture; Opioid; Mu; Fibromyalgia; Pain; Positron emission tomography ID RANDOMIZED CONTROLLED-TRIAL; SYNAPTIC PLASTICITY; SUICIDE VICTIMS; HUMAN BRAIN; PAIN; ELECTROACUPUNCTURE; ANALGESIA; FMRI; FIBROMYALGIA; RESPONSES AB Controversy remains regarding the mechanisms of acupuncture analgesia. A prevailing theory, largely unproven in humans, is that it involves the activation of endogenous opioid antinociceptive systems and mu-opioid receptors (MORs). This is also a neurotransmitter system that mediates the effects of placebo-induced analgesia This Overlap in potential mechanisms may explain the lack of differentiation between traditional acupuncture and either non-traditional or sham acupuncture in multiple controlled clinical trials. We compared both short- and long-term effects of traditional Chinese acupuncture (TA) versus sham acupuncture (SA) treatment on in vivo MOR binding availability in chronic pain patients diagnosed with fibromyalgia (FM). Patients were randomized to receive either TA or SA treatment over the course of 4 weeks. Positron emission tomography (PET) with C-11-carfentanil was performed once during the first treatment session and then repeated a month later following the eighth treatment. Acupuncture therapy evoked short-term increases in MOR binding potential, in Multiple pain and sensory processing regions including the cingulate (dorsal and subgenual). insula, caudate, thalamus, and amygdala. Acupuncture therapy also evoked long-term increases in MOR binding potential in some of the same structures including the cingulate (dorsal and perigenual), caudate, and amygdala. These short- and long-term effects were absent in the sham group where small reductions were observed, an effect more consistent with previous placebo PET studies. Long-term increases in MOR BP following TA were also associated with greater reductions in clinical pain. These findings Suggest that divergent MOR processes may mediate clinically relevant analgesic effects for acupuncture and sham acupuncture, (C) 2009 Elsevier Inc. All rights reserved. C1 [Harris, Richard E.; Clauw, Daniel J.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Zubieta, Jon-Kar] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Zubieta, Jon-Kar] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Zubieta, Jon-Kar] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Scott, David J.] Omneuron Incorp, Menlo Pk, CA 94025 USA. [Napadow, Vitaly] Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Gracely, Richard H.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. RP Harris, RE (reprint author), Chron Pain & Fatigue Res Ctr, 24 Frank Lloyd Wright Dr,POB 385, Ann Arbor, MI 48106 USA. EM reharris@med.umich.edu RI Harris, Richard/F-1307-2011 FU Department of Army [17/002-0018, W81XWH-07-2-0050]; National Institutes of Health [M01-RR000042, R01 AT 001415, K01 AT01111-01, K01-AT002166, P01-AT002048] FX This work was funded by Department of Army grants DAVID (17/002-0018 to DJ.C. and W81XWH-07-2-0050 to R.E.H.) and National Institutes of Health (M01-RR000042 to R.E.H.; R01 AT 001415 to J.K.Z, K01-AT01111-01 to R.E.H., and K01-AT002166 and P01-AT002048 to V.N.). NR 49 TC 89 Z9 97 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2009 VL 47 IS 3 BP 1077 EP 1085 DI 10.1016/j.neuroimage.2009.05.083 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 482YI UT WOS:000268926200035 PM 19501658 ER PT J AU Gray, MA Minati, L Harrison, NA Gianaros, PJ Napadow, V Critchley, HD AF Gray, Marcus A. Minati, Ludovico Harrison, Neil A. Gianaros, Peter J. Napadow, Vitaly Critchley, Hugo D. TI Physiological recordings: Basic concepts and implementation during functional magnetic resonance imaging SO NEUROIMAGE LA English DT Review ID AUTONOMIC NERVOUS-SYSTEM; TIME-SERIES ANALYSIS; SKIN-CONDUCTANCE; ARTIFACT CORRECTION; SIMULTANEOUS EEG; BOLD SIGNAL; HEMODYNAMIC-RESPONSE; NEURAL ACTIVATION; CINGULATE CORTEX; FMRI EXPERIMENTS AB Combining human functional neuroimaging with other forms of psychophysiological measurement, including autonomic monitoring, provides an empirical basis for understanding brain-body interactions. This approach can be applied to characterize unwanted physiological noise, examine the neural control and representation of bodily processes relevant to health and morbidity, and index covert expression of affective and cognitive processes to enhance the interpretation of task-evoked regional brain activity. In recent years. human neuroimaging has been dominated by functional magnetic resonance imaging (fMRI) studies. The spatiotemporal information of fMRI regarding central neural activity is valuably complemented by parallel physiological monitoring, yet Such studies still remain in the minority. This review article highlights fMRI studies that employed Cardiac, vascular, respiratory, electrodermal, gastrointestinal and pupillary psychophysiological indices to address specific questions regarding interaction between brain and bodily state in the context of experience, cognition, emotion and behaviour. Physiological monitoring within the fMRI environment presents specific technical issues, most importantly related to safety. Mechanical and electrical hazards may present clangers to scanned Subjects, operator and/or equipment. Furthermore, physiological monitoring may interfere with the quality of neuroimaging data, or itself be compromised by artefacts induced by the operation of the scanner. We review the Sources of these potential problems and the current approaches and advice to enable the combination of fMRI and physiological monitoring in a safe and effective manner. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved. C1 [Gray, Marcus A.; Minati, Ludovico; Harrison, Neil A.; Critchley, Hugo D.] Univ Surrey, Brighton & Sussex Med Sch, Clin Imaging Sci Ctr, Guildford GU2 5XH, Surrey, England. [Gray, Marcus A.; Minati, Ludovico; Harrison, Neil A.; Critchley, Hugo D.] Univ Surrey, Brighton & Sussex Med Sch, Dept Psychiat, Guildford GU2 5XH, Surrey, England. [Gianaros, Peter J.] Univ Pittsburgh, Ctr Neural Basis Cognit, Dept Psychiat, Pittsburgh, PA 15260 USA. [Napadow, Vitaly] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Cambridge, MA 02138 USA. RP Gray, MA (reprint author), Univ Surrey, Brighton & Sussex Med Sch, Clin Imaging Sci Ctr, Falmer Campus, Guildford GU2 5XH, Surrey, England. EM m.a.gray@bsms.ac.uk RI critchley, hugo/G-9267-2011; Gray, Marcus/F-6521-2013; OI Gray, Marcus/0000-0001-8671-6939; Harrison, Neil/0000-0002-9584-3769 FU NCCAM; National Institutes of Health [P01-AT002048, K01-AT002166, F05-AT003770, R01-AT004714, K01-MH070616, R01-HL 089850]; Wellcome Trust FX Vitaly Napadow was supported by the following grants from NCCAM and the National Institutes of Health, NIH (P01-AT002048, K01-AT002166, F05-AT003770, R01-AT004714). HDC is supported by a programme grant from the Wellcome Trust. PIG is supported by NIH grants K01-MH070616 and R01-HL 089850. NR 130 TC 29 Z9 29 U1 1 U2 25 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2009 VL 47 IS 3 BP 1105 EP 1115 DI 10.1016/j.neuroimage.2009.05.033 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 482YI UT WOS:000268926200038 PM 19460445 ER PT J AU Smith, EE Liang, L Hernandez, A Reeves, MJ Cannon, CP Fonarow, GC Schwamm, LH AF Smith, E. E. Liang, L. Hernandez, A. Reeves, M. J. Cannon, C. P. Fonarow, G. C. Schwamm, L. H. TI Influence of stroke subtype on quality of care in the Get With The Guidelines-Stroke Program SO NEUROLOGY LA English DT Article ID TRANSIENT ISCHEMIC ATTACK; SPONTANEOUS INTRACEREBRAL HEMORRHAGE; INTERDISCIPLINARY WORKING GROUP; AMERICAN-HEART-ASSOCIATION; SPECIAL WRITING GROUP; SUBARACHNOID HEMORRHAGE; RISK-FACTORS; PRIMARY PREVENTION; SERUM-CHOLESTEROL; NEUROLOGY AFFIRMS AB Objective: Little is known about in-hospital care for hemorrhagic stroke. We examined quality of care in intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) admissions in the national Get With The Guidelines-Stroke (GWTG-Stroke) database, and compared them to ischemic stroke (IS) or TIA admissions. Methods: Between April 1, 2003, and December 30, 2007, 905 hospitals contributed 479,284 consecutive stroke and TIA admissions. The proportions receiving each quality of care measure were calculated by dividing the total number of patients receiving the intervention by the total number of patients eligible for the intervention, excluding ineligible patients or those with contraindications to treatment. Logistic regression models were used to determine associations between measure compliance and stroke subtype, controlling for patient and hospital characteristics. Results: Stroke subtypes were 61.7% IS, 23.8% TIA, 11.1% ICH, and 3.5% SAH. Performance on care measures was generally lower in ICH and SAH compared to IS/TIA, including guideline-recommended measures for deep venous thrombosis (DVT) prevention (for ICH) and smoking cessation (for SAH) (multivariable-adjusted p < 0.001 for all comparisons). Exceptions were that ICH patients were more likely than IS/TIA to have door-to-CT times < 25 minutes (multivariable-adjusted p < 0.001) and to undergo dysphagia screening (multivariable-adjusted p < 0.001). Time spent in the GWTG-Stroke program was associated with improvements in many measures of care for ICH and SAH patients, including DVT prevention and smoking cessation therapy (multivariable-adjusted p < 0.001). Conclusions: Many hospital-based acute care and prevention measures are underutilized in intracerebral hemorrhage and subarachnoid hemorrhage compared to ischemic stroke /TIA. Duration of Get With The Guidelines-Stroke participation is associated with improving quality of care for hemorrhagic stroke. Neurology (R) 2009; 73: 709-716 C1 [Smith, E. E.] Univ Calgary, Dept Clin Neurosci, Foothills Med Ctr, Hotchkiss Brain Inst,Calgery Stroke Program, Calgary, AB T2N 2T9, Canada. [Liang, L.; Hernandez, A.] Duke Clin Res Inst, Durham, NC USA. [Reeves, M. J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Cannon, C. P.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Fonarow, G. C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Schwamm, L. H.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Smith, EE (reprint author), Univ Calgary, Dept Clin Neurosci, Foothills Med Ctr, Hotchkiss Brain Inst,Calgery Stroke Program, 1403 29th St NW, Calgary, AB T2N 2T9, Canada. EM eesmith@ucalgary.ca RI Hernandez, Adrian F./A-7818-2016; OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU NINDS NIH HHS [R01NS062028] NR 31 TC 16 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 1 PY 2009 VL 73 IS 9 BP 709 EP 716 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 489SY UT WOS:000269444200010 PM 19720978 ER PT J AU Tsai, PH Mendez, MF AF Tsai, Po-Heng Mendez, Mario F. TI AKINETOPSIA IN THE POSTERIOR CORTICAL VARIANT OF ALZHEIMER DISEASE SO NEUROLOGY LA English DT Editorial Material ID MOTION BLINDNESS; ATROPHY; DAMAGE C1 [Mendez, Mario F.] VA Greater Los Angeles Healthcare Syst, Neurobehav Unit, Los Angeles, CA 90073 USA. [Tsai, Po-Heng] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu NR 7 TC 8 Z9 8 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 1 PY 2009 VL 73 IS 9 BP 731 EP + PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 489SY UT WOS:000269444200014 PM 19720982 ER PT J AU Butler, MA Corboy, JR Filley, CM AF Butler, Michelle A. Corboy, John R. Filley, Christopher M. TI How the Conflict between American Psychiatry and Neurology Delayed the Appreciation of Cognitive Dysfunction in Multiple Sclerosis SO NEUROPSYCHOLOGY REVIEW LA English DT Review DE Cognition; History of medicine; History of psychiatry/neurology; Demyelinating disease; Schemas; Multiple sclerosis ID DISABILITY STATUS SCALE; DIAGNOSTIC-CRITERIA; IMPAIRMENT; HISTORY; DEMENTIA; PATTERNS; CONCEPTUALIZATION; MEDICINE; DISEASE; STATE AB Whereas cognitive deficits in multiple sclerosis (MS) were documented in the original clinicopathological description by Charcot, the extent and nature of cognitive dysfunction was poorly understood in the U.S. until over a century later. Our objective was to discern reasons for this misunderstanding and to examine forces shifting this topic to center stage of research and increased awareness in clinical practice. We hypothesized that during the 19th century, conflict between psychiatrists and neurologists over control of treatment of the mentally ill fueled a misunderstanding of the nature of MS which led neurologists to treat diseases of the body, and psychiatrists, diseases of the mind. The importance of cognitive deficits in MS was thus minimized until scientific breakthroughs could once again bring them to light. As the rift between disciplines peaked, awareness of cognitive deficits diminished, and vice versa. This may have been one contributing factor affecting how MS was mistakenly conceptualized for a century. C1 [Butler, Michelle A.] USAF Acad, HQ DFBL, Colorado Springs, CO 80840 USA. [Corboy, John R.; Filley, Christopher M.] Univ Colorado, Denver Sch Med, Dept Neurol, Denver, CO 80202 USA. [Filley, Christopher M.] Univ Colorado, Denver Sch Med, Dept Psychiat, Denver, CO 80202 USA. [Corboy, John R.; Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Butler, MA (reprint author), USAF Acad, HQ DFBL, 2354 Fairchild Dr,Ste 6L101B, Colorado Springs, CO 80840 USA. EM michelle.butler@usafa.edu NR 89 TC 8 Z9 8 U1 0 U2 2 PU CONSULTANTS BUREAU/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1040-7308 J9 NEUROPSYCHOL REV JI Neuropsychol. Rev. PD SEP PY 2009 VL 19 IS 3 BP 399 EP 410 DI 10.1007/s11065-009-9089-y PG 12 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA 495SE UT WOS:000269914500010 PM 19373561 ER PT J AU Perlis, RH Patrick, A Smoller, JW Wang, PS AF Perlis, Roy H. Patrick, Amanda Smoller, Jordan W. Wang, Philip S. TI When is Pharmacogenetic Testing for Antidepressant Response Ready for the Clinic? A Cost-effectiveness Analysis Based on Data from the STAR*D Study SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE pharmacogenetics; major depressive disorder; cost effectiveness; serotonin ID MAJOR DEPRESSIVE DISORDER; PRIMARY-CARE; SEROTONIN TRANSPORTER; CITALOPRAM TREATMENT; ECONOMIC EVALUATIONS; SUICIDAL IDEATION; MANAGED CARE; OUTCOMES; HEALTH; POLYMORPHISMS AB The potential of personalized medicine to transform the treatment of mood disorders has been widely touted in psychiatry, but has not been quantified. We estimated the costs and benefits of a putative pharmacogenetic test for antidepressant response in the treatment of major depressive disorder (MDD) from the societal perspective. Specifically, we performed cost-effectiveness analyses using state-transition probability models incorporating probabilities from the multicenter STAR*D effectiveness study of MDD. Costs and quality-adjusted life years (QALYs) were compared for sequential antidepressant trials, with or without guidance from a pharmacogenetic test for differential response to selective serotonin reuptake inhibitors (SSRIs). Likely SSRI responders received an SSRI, whereas likely nonresponders received the norepinephrine/dopamine reuptake inhibitor bupropion. For a 40-year old with MDD, applying the pharmacogenetic test and using the non-SSRI bupropion for those at higher risk for nonresponse cost $93 520 per additional QALY compared with treating all patients with an SSRI first and switching sequentially in the case of nonremission. Cost per QALY dropped below $50 000 for tests with remission rate ratios as low as 1.5, corresponding to odds ratios similar to 1.8-2.0. Tests for differential antidepressant response could thus become cost effective under certain circumstances. These circumstances, particularly availability of alternative treatment strategies and test effect sizes, can be estimated and should be considered before these tests are broadly applied in clinical settings. Neuropsychopharmacology (2009) 34, 2227-2236; doi: 10.1038/npp.2009.50; published online 3 June 2009 C1 [Perlis, Roy H.; Smoller, Jordan W.] Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Perlis, Roy H.; Smoller, Jordan W.] Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat Genet Program, Boston, MA 02114 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Patrick, Amanda] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02114 USA. [Wang, Philip S.] NIMH, Bethesda, MD 20892 USA. RP Perlis, RH (reprint author), Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM rperlis@partners.org FU NIMH [K23-MH67060]; NARSAD [R01MH6194]; Sydney R Baer, Jr Foundation; Bowman Family Foundation FX This work was supported by NIMH K23-MH67060, NARSAD and the Sydney R Baer, Jr Foundation, and the Bowman Family Foundation (Dr Perlis) and NIMH R01MH6194 (Dr Wang). No pharmaceutical company was involved in any way in initiating, conducting, or supporting this research. NR 54 TC 36 Z9 37 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2009 VL 34 IS 10 BP 2227 EP 2236 DI 10.1038/npp.2009.50 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 482VY UT WOS:000268919100004 PM 19494805 ER PT J AU Dracheva, S Lyddon, R Barley, K Marcus, SM Hurd, YL Byne, WM AF Dracheva, Stella Lyddon, Rebecca Barley, Kevin Marcus, Sue M. Hurd, Yasmin L. Byne, William M. TI Editing of Serotonin 2C Receptor mRNA in the Prefrontal Cortex Characterizes High-Novelty Locomotor Response Behavioral Trait SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin 2C receptor; mRNA editing; drug addiction; rat; high and low responders; prefrontal cortex ID VENTRAL TEGMENTAL AREA; SELF-ADMINISTRATION BEHAVIOR; RAT NUCLEUS-ACCUMBENS; 5-HT2C RECEPTOR; DOPAMINE RELEASE; IN-VIVO; INDIVIDUAL-DIFFERENCES; CONSTITUTIVE ACTIVITY; COCAINE; NEURONS AB Serotonin 2C receptor (5-HT(2C)R) exerts a major inhibitory influence on dopamine (DA) neurotransmission within the mesocorticolimbic DA pathway that is implicated in drug reward and goal-directed behaviors. 5-HT(2C)R pre-mRNA undergoes adenosine-to-inosine editing, generating numerous receptor isoforms in brain. As editing influences 5-HT(2C)R activity, individual differences in editing might influence dopaminergic function and, thereby, contribute to interindividual vulnerability to drug addiction. Liability to drug-related behaviors in rats can be predicted by their level of motor activity in response to a novel environment. Rats with a high locomotor response (high responders; HRs) exhibit enhanced acquisition and maintenance of drug self-administration compared to rats with a low response (low responders; LRs). We here examined 5-HT(2C)R mRNA editing and expression in HR and LR phenotypes to investigate the relationship between 5-HT(2C)R function and behavioral traits relevant to drug addiction vulnerability. Three regions of the mesocorticolimbic circuitry (ventral tegmental area (VTA), nucleus accumbens (NuAc) shell, and medial prefrontal cortex (PFC)) were examined. 5-HT(2C)R mRNA expression and editing were significantly higher in the NuAc shell compared with both the PFC and VTA, implying significant differences in function (including constitutive activity) among 5-HT(2C)R neuronal populations within the circuitry. The regional differences in editing could, at least in part, arise from the variations in expression levels of the editing enzyme, ADAR2, and/or from the variations in the ADAR2/ADAR1 ratio observed in the study. No differences in the 5-HT(2C)R expression were detected between the behavioral phenotypes. However, editing was higher in the PFC of HRs vs LRs, implicating this region in the pathophysiology of drug abuse liability. Neuropsychopharmacology (2009) 34, 2237-2251; doi: 10.1038/npp.2009.51; published online 3 June 2009 C1 [Dracheva, Stella; Hurd, Yasmin L.; Byne, William M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Dracheva, Stella; Lyddon, Rebecca; Barley, Kevin; Marcus, Sue M.; Hurd, Yasmin L.; Byne, William M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Dracheva, S (reprint author), Bronx VA Med Ctr, Psychiat Res 4F-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Stella.Dracheva@mssm.edu OI Barley, Kevin/0000-0003-1604-1694 FU National Institute on Drug Abuse [DA022264]; VISN3 Mental Illness Research and Education Clinical Center FX This work was supported by the National Institute on Drug Abuse grant DA022264 (SD), the VISN3 Mental Illness Research and Education Clinical Center (SD) and the use of facilities at the JJ Peters VA Medical Center, Bronx, NY where SD and YH are Research Health Science Specialists and WB is a Staff Physician. We are grateful to Ms Nayna Patel and Mr Benjamin Chin for their superb technical assistance. NR 81 TC 22 Z9 22 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2009 VL 34 IS 10 BP 2237 EP 2251 DI 10.1038/npp.2009.51 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 482VY UT WOS:000268919100005 PM 19494808 ER PT J AU Yang, YS Koontz, AM Triolo, RJ Cooper, RA Boninger, ML AF Yang, Yu-Sheng Koontz, Alicia M. Triolo, Ronald J. Cooper, Rory A. Boninger, Michael L. TI Biomechanical Analysis of Functional Electrical Stimulation on Trunk Musculature During Wheelchair Propulsion SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE Wheelchair; Spinal cord injury; Shoulder; Kinetics; Kinematics; Electromyography; Functional electrical stimulation ID SPINAL-CORD-INJURY; MECHANICAL EFFICIENCY; SHOULDER MUSCLES; UPPER EXTREMITY; PUSHRIM FORCES; 2 SPEEDS; LEVEL; INDIVIDUALS; PHYSIOLOGY; ENERGY AB Background. The objective of this study was to examine how surface electrical stimulation of trunk musculature influences the kinematic, kinetic, and metabolic characteristics, as well as shoulder muscle activity, during wheelchair propulsion. Methods. Eleven participants with spinal cord injury propelled their own wheelchairs on a dynamometer at a speed of 1.3 m/s for three 5-minute trials. During a propulsion trial, 1 of 3 stimulation levels (HIGH, LOW, and OFF) was randomly applied to the participant's abdominal and back muscle groups with a surface functional electrical stimulation device. Propulsion kinetics, trunk kinematics, metabolic responses, and surface electromyographic (EMG) activity of 6 shoulder muscles were collected synchronously. Kinetic, kinematic, and EMG variables were recorded during 3 time intervals (30 seconds each) within a 5-minute trial. Metabolic variables were recorded through the entire 5-minute trial. Results. Participants with HIGH stimulation increased their gross mechanical efficiency (P = .05) during wheelchair propulsion. No differences were found in shoulder EMG activity, energy expenditure, and trunk motion between stimulation levels. Conclusion. Functional electrical stimulation on the trunk musculature has potential advantages in helping manual wheelchair users with spinal cord injury improve propulsion efficiency without placing additional demands on shoulder musculature. C1 [Yang, Yu-Sheng; Koontz, Alicia M.; Cooper, Rory A.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Koontz, Alicia M.; Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Koontz, Alicia M.; Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Triolo, Ronald J.] Case Western Reserve Univ, Louis Stokes Cleveland Vet Affairs Med Ctr, Cleveland, OH 44106 USA. [Triolo, Ronald J.] Case Western Reserve Univ, Dept Orthopaed, Cleveland, OH 44106 USA. [Triolo, Ronald J.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Yang, Yu-Sheng] Kaohsiung Med Univ, Dept Occupat Therapy, Fac Occupat Therapy, Coll Hlth Sci, Kaohsiung, Taiwan. [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Med Ctr Hlth Syst, Pittsburgh, PA USA. RP Koontz, AM (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 7180 Highland Dr,151R1-H, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu RI Yang, Yu-Sheng/D-4525-2009; OI Yang, Yu-Sheng/0000-0002-2767-9354; Boninger, Michael/0000-0001-6966-919X FU US Department of Veterans Affairs, Rehabilitation Research and Development [B3043-C]; American Society FX This research was supported by the US Department of Veterans Affairs, Rehabilitation Research and Development (B3043-C), and American Society of Biomechanics Graduate Student Grant-In-Aid (2004). NR 40 TC 7 Z9 7 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD SEP PY 2009 VL 23 IS 7 BP 717 EP 725 DI 10.1177/1545968308331145 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 487ZB UT WOS:000269317100010 PM 19261768 ER PT J AU Schmahmann, JD MacMore, J Vangel, M AF Schmahmann, J. D. MacMore, J. Vangel, M. TI CEREBELLAR STROKE WITHOUT MOTOR DEFICIT: CLINICAL EVIDENCE FOR MOTOR AND NON-MOTOR DOMAINS WITHIN THE HUMAN CEREBELLUM SO NEUROSCIENCE LA English DT Review DE cerebellum; ataxia; motor control; functional topography ID COGNITIVE-AFFECTIVE SYNDROME; ARTERY TERRITORY INFARCTS; ATAXIA RATING-SCALE; RHESUS-MONKEY; FUNCTIONAL-ORGANIZATION; DISCONNEXION SYNDROMES; PREFRONTAL CORTEX; BASIS PONTIS; REPRESENTATION; INVOLVEMENT AB Objective. To determine whether there are non-motor regions of cerebellum in which sizeable infarcts have little or no impact on motor control. Experimental procedures. We evaluated motor deficits in patients following cerebellar stroke using a modified version of the International Cooperative Ataxia Rating Scale (MICARS). Lesion location was determined using magnetic resonance imaging (MRI) and computerized axial tomography (CT). Patients were grouped by stroke location-Group 1, stroke within the anterior lobe (lobules I-V); Group 2, anterior lobe and lobule VI; Group 3, posterior lobe (lobules VI-IX; including flocculonodular lobe, lobule X); Group 4, posterior lobe but excluding lobule VI (i.e. lobules VII-X); Group 5, stroke within anterior lobe plus posterior lobe. Results. Thirty-nine patients were examined 8.0 +/- 6.0 days following stroke. There were no Group 1 patients. As mean MICARS scores for Groups 2 through 5 differed significantly (one-way analysis of variance, F(3,35)=10.9, P=0.000 03), post hoc Tukey's least significant difference tests were used to compare individual groups. Group 2 MICARS scores (n=6; mean +/- SD, 20.2 +/- 6.9) differed from Group 3 (n=6; 7.2 +/- 3.8; P=0.01) and Group 4 (n=13; 2.5 +/- 2.0; P=0.000 02); Group 5 (n=14; 18.6 +/- 12.8) also differed from Group 3 (P=0.009) and Group 4 (P=0.000 02). There were no differences between Groups 2 and 5 (P=0.71), or between Group 3 and Group 4 (P=0.273). However, Group 3 differed from Group 4 when analyzed with a two-sample t-test unadjusted for multiple comparisons (P=0.03). Thus, the cerebellar motor syndrome resulted from stroke in the anterior lobe, but not from stroke in lobules VII-X (Groups 2 plus 5, n=20, MICARS 19.1 +/- 11.2, vs. Group 4; P=0.000 002). Strokes involving lobule VI produced minimal motor impairment. Conclusion. These findings demonstrate that cerebellar stroke does not always result in motor impairment, and they provide clinical evidence for topographic organization of motor versus nonmotor functions in the human cerebellum. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Schmahmann, J. D.; MacMore, J.] Massachusetts Gen Hosp, Dept Neurol, Ataxia Unit, Cognit Behav Neurol Unit, Boston, MA 02114 USA. [Schmahmann, J. D.; MacMore, J.; Vangel, M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vangel, M.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ataxia Unit, Cognit Behav Neurol Unit, Suite 340,Charles River Plaza S,175 Cambridge St, Boston, MA 02114 USA. EM jschmahmann@partners.org FU Birmingham Foundation; [RO1 MH067980] FX Supported in part by RO1 MH067980, and the Birmingham Foundation. Presented in part to the 131st annual meeting of the American Neurological Association, Chicago, October 2006. The authors express their gratitude to Catherine Stoodley, Marygrace Neal, the Partners neurology faculty and residents, and our patients and their families. NR 62 TC 63 Z9 64 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD SEP 1 PY 2009 VL 162 IS 3 BP 852 EP 861 DI 10.1016/j.neuroscience.2009.06.023 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 479UB UT WOS:000268685400029 PM 19531371 ER PT J AU Bouazoune, K Miranda, TB Jones, PA Kingston, RE AF Bouazoune, Karim Miranda, Tina B. Jones, Peter A. Kingston, Robert E. TI Analysis of individual remodeled nucleosomes reveals decreased histone-DNA contacts created by hSWI/SNF SO NUCLEIC ACIDS RESEARCH LA English DT Article ID YEAST SWI/SNF COMPLEX; SWI-SNF COMPLEX; IN-VIVO; FACILITATED BINDING; OCTAMER TRANSFER; SINGLE-MOLECULE; CHROMATIN; RSC; TRANSLOCATION; DISPLACEMENT AB Chromatin remodeling enzymes use the energy of ATP hydrolysis to alter histone-DNA contacts and regulate DNA-based processes in eukaryotes. Whether different subfamilies of remodeling complexes generate distinct products remains uncertain. We have developed a protocol to analyze nucleosome remodeling on individual products formed in vitro. We used a DNA methyltransferase to examine DNA accessibility throughout nucleosomes that had been remodeled by the ISWI and SWI/SNF families of enzymes. We confirmed that ISWI-family enzymes mainly created patterns of accessibility consistent with canonical nucleosomes. In contrast, SWI/SNF-family enzymes generated widespread DNA accessibility. The protection patterns created by these enzymes were usually located at the extreme ends of the DNA and showed no evidence for stable loop formation on individual molecules. Instead, SWI/SNF family proteins created extensive accessibility by generating heterogeneous products that had fewer histone DNA contacts than a canonical nucleosome, consistent with models in which a canonical histone octamer has been 'pushed' off of the end of the DNA. C1 [Miranda, Tina B.; Jones, Peter A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Urol & Biochem & Mol Biol, Los Angeles, CA 90089 USA. [Bouazoune, Karim; Kingston, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol & Genet, Boston, MA 02114 USA. RP Jones, PA (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Urol & Biochem & Mol Biol, Los Angeles, CA 90089 USA. EM jones_p@ccnt.usc.edu; kingston@molbio.mgh.harvard.edu FU American Cancer Society; National Institutes of Health [CA82422, GM48045] FX American Cancer Society postdoctoral fellowship (to T.B.M.); National Institutes of Health grant CA82422 (to P.A.J.); National Institutes of Health grant GM48045 (to R.E.K.). Funding for open access charge: GM48045. NR 77 TC 22 Z9 22 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP PY 2009 VL 37 IS 16 BP 5279 EP 5294 DI 10.1093/nar/gkp524 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 516UO UT WOS:000271569000005 PM 19567737 ER PT J AU Levi, AJ Simmonds, KE Taylor, D AF Levi, Amy J. Simmonds, Katherine E. Taylor, Diana TI The Role of Nursing in the Management of Unintended Pregnancy SO NURSING CLINICS OF NORTH AMERICA LA English DT Article DE Unintended pregnancy; Reproductive health; Reproductive health counseling; Nursing's role in unintended pregnancy management; Nursing advocacy in unintended pregnancy ID UNITED-STATES; PRECONCEPTIONAL WELLNESS; WOMEN; CARE AB This article explores the role of nurses in the prevention, management, and treatment of unintended pregnancy. All nurses have a responsibility to understand the importance of reproductive health care in the primary care of women and their families, and to be prepared to respond to patients' needs for the prevention and management of unintended pregnancy. A public health framework provides an opportunity to identify the role of the nurse in primary, secondary, and tertiary prevention strategies that can contribute to the management of unintended pregnancy for the health of women and their families. Nursing education and the role of nurses in advocacy for reproductive health concerns are also addressed. C1 [Levi, Amy J.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Sch Med, San Francisco, CA 94110 USA. [Simmonds, Katherine E.] Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Nursing, Charlestown, MA 02129 USA. [Taylor, Diana] Univ Calif San Francisco, Sch Nursing, Dept Family Hlth Care Nursing, San Francisco, CA 94143 USA. RP Levi, AJ (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Sch Med, 1001 Potrero Ave,6D-29, San Francisco, CA 94110 USA. EM levia@obgyn.ucsf.edu NR 41 TC 3 Z9 3 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 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD SEP PY 2009 VL 44 IS 3 BP 301 EP + DI 10.1016/j.cnur.2009.06.007 PG 15 WC Nursing SC Nursing GA 496CN UT WOS:000269946200005 PM 19683092 ER PT J AU Buerhaus, PI Donelan, K DesRoches, C Hess, R AF Buerhaus, Peter I. Donelan, Karen DesRoches, Catherine Hess, Robert TI Still Making Progress to Improve the Hospital Workplace Environment? Results from the 2008 National Survey Of Registered Nurses SO NURSING ECONOMICS LA English DT Article AB Despite the majority of RNs perceiving a shortage of nurses, findings from the 2008 National Survey of RNs indicate the hospital workplace improved in several areas compared to a 2006 survey. Improvements included the time RNs spend with patients, quality of nursing care, and a decreasing impact of the shortage on delaying nurses' responses to pages or calls, staff communication, patients' wait time for surgery, and timeliness and efficiency of care. Areas the environment was perceived to have worsened included overtime hours, sexual harassment/hostile, and physical violence. RNs hold mixed views about the consequences of reporting errors and mistakes with a majority agreeing that reporting them had led to positive changes to prevent future errors, but that mistakes were held against them. Overall, results suggest that hospital managers can be reassured that their efforts to improve the workplace environment are having their intended effect but, at the same time, important areas for improvement remain. C1 [Buerhaus, Peter I.] Vanderbilt Univ, Med Ctr, Ctr Interdisciplinary Hlth Workforce Studies, Inst Med & Publ Hlth, Nashville, TN 37203 USA. [DesRoches, Catherine] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Hess, Robert] Gannett Healthcare Grp, Falls Church, VA USA. RP Buerhaus, PI (reprint author), Vanderbilt Univ, Med Ctr, Ctr Interdisciplinary Hlth Workforce Studies, Inst Med & Publ Hlth, Nashville, TN 37203 USA. NR 5 TC 13 Z9 14 U1 0 U2 5 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD SEP-OCT PY 2009 VL 27 IS 5 BP 289 EP 301 PG 13 WC Nursing SC Nursing GA 506UC UT WOS:000270800900003 PM 19927444 ER PT J AU Connor, K McNeese-Smith, D van Servellen, G Chang, B Lee, M Cheng, E Hajar, A Vickrey, BG AF Connor, Karen McNeese-Smith, Donna van Servellen, Gwen Chang, Betty Lee, Martin Cheng, Eric Hajar, Abdulrahman Vickrey, Barbara G. TI Insight Into Dementia Care Management Using Social-Behavioral Theory and Mixed Methods SO NURSING RESEARCH LA English DT Article DE care management; dementia; factor analysis ID SERVICE USE; CAREGIVERS; INTERVENTION; STRAIN AB Background. For health organizations (private and public) to advance their care-management programs, to use resources effectively and efficiently, and to improve patient outcomes, it is germane to isolate and quantify care-management activities and to identify overarching domains. Objectives: The aims of this study were to identify and report on an application of mixed methods of qualitative statistical techniques, based on a theoretical framework, and to construct variables for factor analysis and exploratory factor analytic steps for identifying domains of dementia care management. Methods: Care-management activity data were extracted from the care plans of 181 pairs of individuals (with dementia and their informal caregivers) who had participated in the intervention arm of a randomized controlled trial of a dementia care-management program. Activities were organized into types, using card-sorting methods, influenced by published theoretical constructs on self-efficacy and general strain theory. These activity types were mapped in the initial data set to construct variables for exploratory factor analysis. Principal components extraction with varimax and promax rotations was used to estimate the number of factors. Cronbach's alpha was calculated for the items in each factor to assess internal consistency reliability. Results: The two-phase card-sorting technique yielded 45 activity types out of 450 unique activities. Exploratory factor analysis produced four care-management domains (factors): behavior management, clinical strategies and caregiver support, community agency, and safety. Internal consistency reliability (Cronbach's alpha) of items for each factor ranged from .63 for the factor "safety" to .89 for the factor "behavior management" (Factor 1). Discussion: Applying a systematic method to a large set of care-management activities can identify a parsimonious number of higher order categories of variables and factors to guide the understanding of dementia care-management processes. Further application of this methodology in outcome analyses and to other data sets is necessary to test its practicality. C1 [Connor, Karen; Cheng, Eric; Vickrey, Barbara G.] Vet Adm Greater Los Angeles Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Dept Neurol, Los Angeles, CA 90073 USA. [Connor, Karen; Cheng, Eric; Vickrey, Barbara G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [McNeese-Smith, Donna; van Servellen, Gwen; Chang, Betty] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Lee, Martin] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Lee, Martin] Vet Adm Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. RP Connor, K (reprint author), Vet Adm Greater Los Angeles Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Dept Neurol, Los Angeles, CA 90073 USA. EM kiconnor@ucla.edu FU University of Los Angeles, School of Nursing, Audrienne H. Mosley Scholarship FX This work was supported by University of Los Angeles, School of Nursing, Audrienne H. Mosley Scholarship. NR 37 TC 4 Z9 4 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD SEP-OCT PY 2009 VL 58 IS 5 BP 348 EP 358 PG 11 WC Nursing SC Nursing GA 503HK UT WOS:000270524100008 PM 19752675 ER PT J AU Patti, ME Houten, SM Bianco, AC Bernier, R Larsen, PR Holst, JJ Badman, MK Maratos-Flier, E Mun, EC Pihlajamaki, J Auwerx, J Goldfine, AB AF Patti, Mary-Elizabeth Houten, Sander M. Bianco, Antonio C. Bernier, Raquel Larsen, P. Reed Holst, Jens J. Badman, Michael K. Maratos-Flier, Eleftheria Mun, Edward C. Pihlajamaki, Jussi Auwerx, Johan Goldfine, Allison B. TI Serum Bile Acids Are Higher in Humans With Prior Gastric Bypass: Potential Contribution to Improved Glucose and Lipid Metabolism SO OBESITY LA English DT Article ID WEIGHT-LOSS; PEPTIDE-YY; POSTPRANDIAL CONCENTRATIONS; INSULIN SENSITIVITY; DIABETES-MELLITUS; BARIATRIC SURGERY; GLYCEMIC CONTROL; PLASMA GHRELIN; CHOLECYSTECTOMY; COLESEVELAM AB The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2 thyroid hormone deiodinase. Altered gastrointestinal anatomy following GB could affect enterohepatic recirculation of bile acids. We assessed whether circulating bile acid concentrations differ in patients who previously underwent GB, which might then contribute to improved metabolic homeostasis. We performed cross-sectional analysis of fasting serum bile acid composition and both fasting and post-meal metabolic variables, in three subject groups: (i) post-GB surgery (n = 9), (ii) without GB matched to preoperative BMI of the index cohort (n = 5), and (iii) without GB matched to current BMI of the index cohort (n = 10). Total serum bile acid concentrations were higher in GB (8.90 +/- 4.84 mu mol/l than in both overweight (3.59 +/- 1.95, P = 0.005, Ov) and severely obese (3.86 +/- 1.51, P = 0.045, MOb). Bile acid subfractions taurochenodeoxycholic, taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic acids were all significantly higher in GB compared to Ov (P < 0.05). Total bile acids were inversely correlated with 2-h post-meal glucose (r = -0.59, P < 0.003) and fasting triglycerides (r = -0.40, P = 0.05), and positively correlated with adiponectin (r = -0.48, P < 0.02) and peak glucagon-like peptide-1 (GLP-1) (r = 0.58, P < 0.003). Total bile acids strongly correlated inversely with thyrotropic hormone (TSH) (r = -0.57, P = 0.004). Together, our data suggest that altered bile acid levels and composition may contribute to improved glucose and lipid metabolism in patients who have had GB. C1 [Patti, Mary-Elizabeth; Larsen, P. Reed; Badman, Michael K.; Maratos-Flier, Eleftheria; Mun, Edward C.; Pihlajamaki, Jussi; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Patti, Mary-Elizabeth; Bernier, Raquel; Pihlajamaki, Jussi; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Houten, Sander M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Chem, Lab Genet Metab Dis, NL-1105 AZ Amsterdam, Netherlands. [Houten, Sander M.] Univ Amsterdam, Acad Med Ctr, Dept Pediat, NL-1105 AZ Amsterdam, Netherlands. [Bianco, Antonio C.] Univ Miami, Sch Med, Miami, FL USA. [Larsen, P. Reed; Mun, Edward C.; Goldfine, Allison B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Holst, Jens J.] Univ Copenhagen, Panum Inst, Dept Biomed Sci, DK-2200 Copenhagen, Denmark. [Badman, Michael K.; Maratos-Flier, Eleftheria] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. [Auwerx, Johan] ULP, CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. [Auwerx, Johan] Inst Clin Souris, Illkirch Graffenstaden, France. RP Patti, ME (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM mary.elizabeth.patti@joslin.harvard.edu RI Bianco, Antonio/A-4965-2008; OI Bianco, Antonio/0000-0001-7737-6813; Houten, Sander/0000-0002-6167-9147; Holst, Jens Juul/0000-0001-6853-3805 FU NIH [DK062948, DK060837, DK 067320]; Juvenile Diabetes Research Foundation [K23-DK02795]; American Diabetes Association Career Development Award [06-CD-07, DK65055]; Picower Institute [M01 RR001032, DK36836]; Danish Medical Research Council; Novo Nordisk Foundation FX Supported by NIH DK062948 (M.-E.P), DK060837 (M.-E.P and A.B.G), Juvenile Diabetes Research Foundation (M.-E.P and A.B.G), K23-DK02795 and American Diabetes Association Career Development Award 06-CD-07 (A.B.G), DK65055 (Bianco), Picower Institute (M.K.B and E.M.-F), M01 RR001032 (General Clinical Research Center), and DK36836 (Diabetes and Endocrinology Research Center, Joslin Diabetes Center). Dr Auwerx thanks CNRS, INSERM, Universite Louis Pasteur and NIH (DK 067320) for grant support. Dr Holst has been supported by the Danish Medical Research Council and the Novo Nordisk Foundation. We appreciate the technical expertise of Henk Overmars, Lone Bagger Thielsen, Petr Jarolim, and assistance of Stanley Vance, and Rebecca Friedrichs. NR 40 TC 214 Z9 222 U1 5 U2 27 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 SEP PY 2009 VL 17 IS 9 BP 1671 EP 1677 DI 10.1038/oby.2009.102 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 490TG UT WOS:000269527200005 PM 19360006 ER PT J AU Misra, M Tsai, PM Mendes, N Miller, KK Klibanski, A AF Misra, Madhusmita Tsai, Patrika M. Mendes, Nara Miller, Karen K. Klibanski, Anne TI Increased Carbohydrate Induced Ghrelin Secretion in Obese vs. Normal-weight Adolescent Girls SO OBESITY LA English DT Article ID PEPTIDE YY LEVELS; FOOD-INTAKE; PLASMA GHRELIN; CIRCULATING GHRELIN; ANOREXIA-NERVOSA; ENDOCRINE-CELLS; OVERWEIGHT CHILDREN; ACYLATED PEPTIDE; GUT HORMONE; MEAL AB Orexigenic and anorexigenic pathways mediate food intake and may be affected by meal composition. Our objective was to determine whether changes in levels of active ghrelin and peptide YY (PYY) differ in obese vs. normal-weight adolescent girls following specific macronutrient intake and predict hunger and subsequent food intake. We enrolled 26 subjects: 13 obese and 13 normal-weight girls, 12-18 years old, matched for maturity (as assessed by bone age) and race. Subjects were assigned a high-carbohydrate, high-protein, and high-fat breakfast in random order. Active ghrelin and PYY were assessed for 4 h after breakfast and 1 h after intake of a standardized lunch. Hunger was assessed using a standardized visual analog scale (VAS). No suppression in active ghrelin levels was noted following macronutrient intake in obese or normal-weight girls. Contrary to expectations, active ghrelin increased in obese girls following the high-carbohydrate breakfast, and the percent increase was higher than in controls (P = 0.046). Subsequent food intake at lunch was also higher (P = 0.03). Following the high-fat breakfast, but not other breakfasts, percent increase in PYY was lower (P = 0.01) and subsequent lunch intake higher (P = 0.005) in obese compared with normal-weight girls. In obese adolescents, specific intake of high-carbohydrate and high-fat breakfasts is associated with greater increases in ghrelin, lesser increases in PYY, and higher intake at a subsequent meal than in controls. Changes in anorexigenic and orexigenic hormones in obese vs. normal-weight adolescents following high-carbohydrate and high-fat meals may influence hunger and satiety signals and subsequent food intake. C1 [Misra, Madhusmita; Tsai, Patrika M.; Mendes, Nara; Miller, Karen K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita; Tsai, Patrika M.; Mendes, Nara; Miller, Karen K.; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA USA. [Misra, Madhusmita] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. EM mmisra@partners.org RI Mendes Estella, Nara/E-4682-2013; Mendes Estella, Nara/A-1469-2015 FU NIH [M01-RR-01066, F32-DK072816, K23 RR018851, DK46200, 5P30DK4620-15] FX We thank the Bionutrition Core of the Clinical Research Center of Massachusetts General Hospital for its help with the protocol and for preparing the test meals. This work was supported in part by NIH grants M01-RR-01066, F32-DK072816, K23 RR018851, DK46200, and 5P30DK4620-15. NR 44 TC 20 Z9 20 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD SEP PY 2009 VL 17 IS 9 BP 1689 EP 1695 DI 10.1038/oby.2009.86 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 490TG UT WOS:000269527200008 PM 19325538 ER PT J AU Mehta, M Waner, M Fay, A AF Mehta, Manisha Waner, Milton Fay, Aaron TI Amniotic Membrane Grafting in the Management of Conjunctival Vascular Malformations SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID SURGICAL TECHNIQUE; LYMPHANGIOMA; RECONSTRUCTION; TRANSPLANTATION; SUPPRESSION; SURFACE AB Purpose: Vascular malformations of the conjunctiva are symptomatically distressing and Surgically challenging. Because their expansive nature necessitates broad conjunctival sacrifice in some cases, epithelial reconstitution may be the best way to avoid symblepharon formation. Amniotic membrane grafts have been useful for conjunctival reconstruction after excision of squamous cell carcinoma and melanoma but have not been used after excision of extensive conjunctival vascular malformations. The authors report the use of amniotic membrane grafts in the management of large conjunctival vascular malformations. Methods: The authors reviewed the clinical records and photographs of 4 patients with combined orbital and conjunctival vascular malformations. The operative details including amniotic membrane grafting and postoperative results were included. The average follow-up period was 9 months. Results: Four patients underwent a total of 6 resections; 2 patients required reoperation. Three of these lesions were lymphatic and 1 was venous. Dehydrated amniotic membrane was initially used in 2 patients who were subsequently grafted with cryopreserved amniotic membrane. Postoperative trauma in 1 case and staged surgery in the other necessitated these second surgeries. Cryopreserved amniotic grafting was successful in all 4 patients with no signs of graft dislocation, rejection, or tumor overgrowth after an average postoperative period of 9 months. Conclusions: Large conjunctival vascular malformations, when extensively resected, leave large, denuded epibulbar and palpebral surfaces that would likely produce severe symblepharon. Conversely, incomplete resection can lead to early recurrent growth. Commercially available amniotic membrane grafts now provide a method for reconstructing these defects, allowing more extensive resection of the tumor. (Ophthal Plast Reconstr Surg 2009;25:371-375) C1 [Mehta, Manisha; Fay, Aaron] Massachusetts Eye & Ear Infirm, Div Ophthalm Plast & Reconstruct Surg, Boston, MA 02114 USA. [Waner, Milton; Fay, Aaron] St Lukes Roosevelt Hosp, Vasc Birthmark Inst New York, New York, NY USA. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, Div Ophthalm Plast & Reconstruct Surg, 243,Charles St, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu NR 25 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP-OCT PY 2009 VL 25 IS 5 BP 371 EP 375 DI 10.1097/IOP.0b013e3181b2f796 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 502WF UT WOS:000270490300008 PM 19966650 ER PT J AU Jakobiec, FA Bhat, P Sutula, F AF Jakobiec, Frederick A. Bhat, Pooja Sutula, Francis TI Winer's Dilated Pore of the Eyelid SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB A 71-year-old woman had a whitish mass of the outer right lower eyelid with an eccentric pore plugged with keratin. Histopathologic evaluation disclosed an epidermoid cyst that opened widely to the surface and was filled with flaky keratin. The wall displayed a proliferation of rete ridge-type structures that projected in the surrounding dermis. The lesion was diagnosed as a dilated pore of Winer and has not recurred after simple excision. C1 [Jakobiec, Frederick A.; Bhat, Pooja] Harvard Univ, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Sutula, Francis] Harvard Univ, Massachusetts Eye & Ear Infirm, Oculoplast Serv, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Room 321, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 5 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP-OCT PY 2009 VL 25 IS 5 BP 411 EP 413 DI 10.1097/IOP.0b013e3181b3b6e3 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 502WF UT WOS:000270490300023 PM 19966665 ER PT J AU Rhee, DJ Krad, O Pasquale, LR AF Rhee, Douglas J. Krad, Omar Pasquale, Louis R. TI Hyphema Following Selective Laser Trabeculoplasty SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article AB Selective laser trabeculoplasty is an effective means of lowering intraocular pressure in patients with openangle glaucoma with a low risk of complications. The authors report a case of hyphema noted 3 days after selective laser trabeculoplasty in a 77-year-old woman with primary open-angle glaucoma. Her intermittent use of oral nonsteroidal anti-inflammatory medications and chronic topical nonsteroidal anti-inflammatory use may have been a contributing risk factor. [Ophthalmic Surg Lasers Imaging 2009;40:493-494.] C1 [Rhee, Douglas J.; Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Krad, Omar] Loyola Univ, Sch Med, Chicago, IL 60611 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 4 TC 11 Z9 13 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1542-8877 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD SEP-OCT PY 2009 VL 40 IS 5 BP 493 EP 494 DI 10.3928/15428877-20090901-09 PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 496ZQ UT WOS:000270020400009 PM 19772274 ER PT J AU Vinegoni, C Razansky, D Hilderbrand, SA Shao, FW Ntziachristos, V Weissleder, R AF Vinegoni, Claudio Razansky, Daniel Hilderbrand, Scott A. Shao, Fangwei Ntziachristos, Vasilis Weissleder, Ralph TI Transillumination fluorescence imaging in mice using biocompatible upconverting nanoparticles SO OPTICS LETTERS LA English DT Article ID SMALL ANIMALS; TOMOGRAPHY; PROTEINS AB We report on a systematic study of upconverting fluorescence signal generation within turbid phantoms and real tissues. An accurate three-point Green's function, describing the forward model of photon propagation, is established and experimentally validated. We further demonstrate, for the first time to our knowledge, autofluorescence-free transillumination imaging of mice that have received biocompatible upconverting nanoparticles. The method holds great promise for artifact-free whole-body visualization of optical molecular probes. (C) 2009 Optical Society of America C1 [Vinegoni, Claudio; Hilderbrand, Scott A.; Shao, Fangwei; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Razansky, Daniel; Ntziachristos, Vasilis] Tech Univ Munich, IBMI, D-85764 Neuherberg, Germany. [Razansky, Daniel; Ntziachristos, Vasilis] Helmholtz Ctr Munich, D-85764 Neuherberg, Germany. RP Vinegoni, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu RI Shao, Fangwei/B-7026-2011; OI Razansky, Daniel/0000-0001-8676-0964 FU National Institutes of Health (NIH) [1-RO1-EB006432] FX C. Vinegoni acknowledges support from National Institutes of Health (NIH) ( grant 1-RO1-EB006432). NR 5 TC 45 Z9 46 U1 0 U2 15 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 SEP 1 PY 2009 VL 34 IS 17 BP 2566 EP 2568 PG 3 WC Optics SC Optics GA 498CO UT WOS:000270114400008 PM 19724491 ER PT J AU Shannon, EG Hart, ES Grottkau, BE AF Shannon, Elizabeth G. Hart, Erin S. Grottkau, Brian E. TI Clavicle Fractures in Children The Essentials SO ORTHOPAEDIC NURSING LA English DT Article ID SHOULDER; MANAGEMENT AB A fracture of the clavicle is a relatively common injury that occurs in patients of all ages. The clavicle is the most commonly fractured long bone in children. The infant, child, or adolescent with a clavicle fracture usually has a history of trauma. Typically, there is localized pain over the fracture, with associated edema and crepitus. Consideration of anatomy within the area of the fracture is essential so that associated injuries can be diagnosed and appropriately treated. Most clavicle fractures heal uneventfully and can be treated nonoperatively. Surgical treatment with open reduction and internal fixation is occurring more often, however, because of potential long-term concerns with functional outcome and decreased range of motion. This article briefly reviews the anatomy and function of the clavicle, common mechanisms of injury, physical examination findings, and conservative as well as surgical management of pediatric clavicle fractures. C1 [Shannon, Elizabeth G.; Hart, Erin S.; Grottkau, Brian E.] MassGen Hosp Children, Dept Orthopaed Surg, Boston, MA USA. RP Shannon, EG (reprint author), MassGen Hosp Children, Dept Orthopaed Surg, Boston, MA USA. NR 23 TC 3 Z9 3 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0744-6020 J9 ORTHOP NURS JI Orthop. Nurs. PD SEP-OCT PY 2009 VL 28 IS 5 BP 210 EP 214 PG 9 WC Nursing; Orthopedics SC Nursing; Orthopedics GA 506YW UT WOS:000270815900002 PM 19820618 ER PT J AU Bhattacharyya, N Lin, HW AF Bhattacharyya, Neil Lin, Harrison W. TI Prevalence and reliability of self-reported authorship disclosures in Otolaryngology-Head and Neck Surgery SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID CONFLICTS-OF-INTEREST; FINANCIAL COMPETING INTERESTS; ROFECOXIB LITIGATION; INDUSTRY; TRIALS; DOCUMENTS; IMPACT; DRUGS AB OBJECTIVE: Determine reliability of self-reported authorship disclosures of potential conflicts of interest in American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF)-sponsored presentations and publications. STUDY DESIGN/SETTING: Retrospective cohort study at academic center. METHODS: Presenters' self-reported disclosures made at the AAO-HNSF annual meeting for calendar years 2006 and 2007 were tabulated. Subsequent publications related to these presentations in the journal Otolaryngology-Head and Neck Surgery were analyzed with respect to disclosures revealed at the time of publication. Discrepancies between annual meeting disclosures and publication print disclosures were identified according to author and presentation/paper. Reliability statistics were computed to determine consistency of disclosure reporting and an analysis of potential conflicts of interest according to discrepancies was performed. RESULTS: Five hundred seventy-eight presenters' disclosures were identified at the annual meeting level, which ultimately led to 153 journal publications. A total of 51 authors (8.8%) with disclosure reporting discrepancies were identified (32 authors: one discrepancy; 11 authors: two discrepancies; eight authors: three or more discrepancies). Overall, a mean of 0.14 discrepancies per author (95% confidence interval: 0.10-0.19 discrepancies) was noted. Analyzed by publication, 39 papers (25.5%) contained one or more disclosure discrepancies among authors, ranging from one discrepancy (11.8% of papers) to nine discrepancies (0.7%), with an average of 2.1 authorship disclosure discrepancies per paper. CONCLUSIONS: A significant percentage of authors' disclosures differ between time of presentation and subsequent publication within otolaryngology. Although valid reasons for these discrepancies may exist, analysis of these discrepancies is important for conflict-of-interest determination. (C) 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. [Bhattacharyya, Neil; Lin, Harrison W.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, 75 Francis St, Boston, MA 02115 USA. EM neiloy@massmed.org NR 21 TC 10 Z9 10 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2009 VL 141 IS 3 BP 311 EP 315 DI 10.1016/j.otohns.2009.06.010 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 491UD UT WOS:000269604300002 PM 19716005 ER PT J AU Lin, HW Aliphas, A Leonard, DS AF Lin, Harrison W. Aliphas, Avner Leonard, David S. TI Membranous band of a first branchial cleft anomaly SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Editorial Material C1 [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lin, Harrison W.; Leonard, David S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Aliphas, Avner] Boston Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA 02118 USA. [Leonard, David S.] Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA. RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM harrison_lin@meei.harvard.edu OI Aliphas, Avner/0000-0001-7053-2051 NR 4 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2009 VL 141 IS 3 BP 420 EP 421 DI 10.1016/j.otohns.2009.04.008 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 491UD UT WOS:000269604300023 PM 19716026 ER PT J AU Fisher, LM Doherty, JK Lev, MH Slattery, WH AF Fisher, Laurel M. Doherty, Joni K. Lev, Michael H. Slattery, William H. TI Concordance of Bilateral Vestibular Schwannoma Growth and Hearing Changes in Neurofibromatosis 2: Neurofibromatosis 2 Natural History Consortium SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Bilateral vestibular schwannoma; Hearing; Mendelian; Neurofibromatosis 2; Tumor growth ID SIMPLE MENDELIAN DISORDERS; ACOUSTIC TUMORS; COMPLEX TRAITS; TYPE-2; GENE; NF2; INDIVIDUALS; SUPPRESSOR; EXPRESSION; PHENOTYPES AB Objective: To examine the relationship between the amount of change in size and associated hearing in bilateral vestibular schwannomas (VSs) in persons with neurofibromatosis 2 (NF2). Study Design: Annual magnetic resonance imaging and audiological examinations were conducted on NF2 patients. Subjects: Fifty-two patients enrolled in the NF2 Natural History Consortium in whom both VSs were untreated. Magnetic resonance imaging and hearing exams were available for at least 2 time points 1 year apart. The 32 males and 20 females had a mean age at diagnosis of 26 years (SD = 18). In 19 (37%) subjects, the NF2 germline mutation could not be identified in the blood ( mosaic). Outcome Measures: Greatest diameter change in tumor size for each of the 2 tumors from first to second evaluation was determined. Differences in amounts of change between the 2 sides and in hearing (4-frequency pure-tone average) were evaluated using multivariate analysis of variance. Results: Overall, the VSs demonstrated significant average growth (p < 0.001), and hearing worsened significantly (p < 0.001) over 1 year. The amount of change in the bigger tumors was not associated with the amount of change in the smaller tumors within each patient. Vestibular schwannoma size changes were not associated with the corresponding hearing changes (Kendall's tau, p = not significant [n.s.]). Conclusion: A significant 1-year change in VS size and hearing occurred in NF2 patients. Clinically, tumor change or hearing deterioration on one VS cannot be used to predict changes in the other VS. This suggests that, although NF2 is a Mendelian disease, the germline genotype-phenotype relationship may resemble that of complex disorders. C1 [Fisher, Laurel M.; Slattery, William H.] House Ear Res Inst, Los Angeles, CA 90057 USA. [Doherty, Joni K.] Univ San Diego, Sch Med, San Diego, CA 92110 USA. [Lev, Michael H.] Massachusetts Gen Hosp, Neuroradiol & Neurovasc Lab, Boston, MA 02114 USA. RP Slattery, WH (reprint author), House Ear Res Inst, 2100 W 3rd St, Los Angeles, CA 90057 USA. EM wslattery@hei.org FU Department of Defense Neurofibromatosis Research [DAMD17-98-1-8612, 17-01-1-0710] FX This research was supported by the Department of Defense Neurofibromatosis Research under award number (DAMD17-98-1-8612 and 17-01-1-0710). Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense. NR 32 TC 27 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD SEP PY 2009 VL 30 IS 6 BP 835 EP 841 DI 10.1097/MAO.0b013e3181b2364c PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 586QR UT WOS:000276926900023 PM 19704365 ER PT J AU Wang, Z Guo, YM Bradesi, S Labus, JS Maarek, JMI Lee, K Winchester, WJ Mayer, EA Holschneider, DP AF Wang, Zhuo Guo, Yumei Bradesi, Sylvie Labus, Jennifer S. Maarek, Jean-Michel I. Lee, Kevin Winchester, Wendy J. Mayer, Emeran A. Holschneider, Daniel P. TI Sex differences in functional brain activation during noxious visceral stimulation in rats SO PAIN LA English DT Article DE Visceral pain; Colorectal distension; Cerebral blood flow; Brain mapping; Sex difference ID IRRITABLE-BOWEL-SYNDROME; CORTICOTROPIN-RELEASING-FACTOR; COLORECTAL DISTENSION; PREFRONTAL CORTEX; SEROTONERGIC ACTIVITY; GENDER-DIFFERENCES; INSULAR CORTEX; RAPHE NUCLEUS; ESTROUS-CYCLE; IBS PATIENTS AB Studies in healthy human subjects and patients with irritable bowel syndrome suggest sex differences in cerebral nociceptive processing. Here we examine sex differences in functional brain activation in the rat during colorectal distention (CRD), a preclinical model of acute visceral pain. [(14)C]-iodoantipyrine was injected intravenously in awake, non-restrained female rats during 60- or 0-mmHg CRD while electromyographic abdominal activity (EMG) and pain behavior were recorded. Regional cerebral blood flow-related tissue radioactivity was analyzed by statistical parametric mapping from autoradiographic images of three-dimensionally reconstructed brains. Sex differences were addressed by comparing the current data with our previously published data collected from male rats. While sex differences in EMG and pain scores were modest, significant differences were noted in functional brain activation. Females showed widespread changes in limbic (amygdala, hypothalamus) and paralimbic structures (ventral striatum, nucleus accumbens, raphe), while males demonstrated broad cortical changes. Sex differences were apparent in the homeostatic afferent network (parabrachial nucleus, thalamus, insular and dorsal anterior cingulate cortices), in an emotional-arousal network (amygdala, locus coeruleus complex), and in cortical areas modulating these networks (prefrontal cortex). Greater activation of the ventromedial prefrontal cortex and broader limbic/paralimbic changes in females suggest greater engagement of affective mechanisms during visceral pain. Greater cortical activation in males is consistent with the concept of greater cortical inhibitory effects on limbic structures in males, which may relate to differences in attentional and cognitive attribution to visceral stimuli. These findings show remarkable similarities to reported sex differences in brain responses to visceral stimuli in humans. (C) 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Holschneider, Daniel P.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90089 USA. [Holschneider, Daniel P.] Univ So Calif, Dept Neurol, Los Angeles, CA 90089 USA. [Holschneider, Daniel P.] Univ So Calif, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA. [Lee, Kevin; Winchester, Wendy J.] GlaxoSmithKline Inc, Neurol & GI Ctr Excellence Drug Discovery, Harlow, Essex, England. [Maarek, Jean-Michel I.; Holschneider, Daniel P.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Wang, Zhuo; Bradesi, Sylvie; Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, Ctr Neurobiol Stress, Los Angeles, CA USA. [Bradesi, Sylvie; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Mayer, Emeran A.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. [Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Wang, Zhuo; Bradesi, Sylvie; Mayer, Emeran A.; Holschneider, Daniel P.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Holschneider, DP (reprint author), Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, 1333 San Pablo St,BMT 403, Los Angeles, CA 90089 USA. EM holschne@usc.edu FU GlaxoSmithKIine; Animal Models Core; Neuroimaging Core of the Center for Neurobiology of Stress, UCLA [NIDDK P50DK064539, NCCAM AT00268] FX Grant support from GlaxoSmithKIine, and the Animal Models Core and the Neuroimaging Core of the Center for Neurobiology of Stress, UCLA (NIDDK P50DK064539, NCCAM AT00268) is acknowledged. There are no conflicts of interest. NR 55 TC 23 Z9 23 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 2009 VL 145 IS 1-2 BP 120 EP 128 DI 10.1016/j.pain.2009.05.025 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 497YN UT WOS:000270101400022 PM 19560270 ER PT J AU Miller, D Richardson, D Eisa, M Bajwa, RJ Jabbari, B AF Miller, Diana Richardson, Diana Eisa, Mahmood Bajwa, Rizma Jalees Jabbari, Bahman TI Botulinum Neurotoxin-A for Treatment of Refractory Neck Pain: A Randomized, Double-Blind Study SO PAIN MEDICINE LA English DT Article DE Botulinum Neurotoxin-A; Neck; Persistent Pain; Placebo; Outcome Measures ID TOXIN TYPE-A; NEUROPATHIC PAIN; CROSSOVER TRIAL; BACK-PAIN; INJECTION; EFFICACY; SAFETY AB Objective. To investigate the efficacy and tolerability of Botulinum neurotoxin-A (BoNT-A) in the patients with refractory neck pain. Background. An analgesic effect is suggested for BoNT-A by a number of animal studies. Two blinded studies suggested efficacy of BoNT-A in a chronic neck pain. Methods. Forty-seven subjects were enrolled in a prospective, double-blind, placebo-controlled study. A total of 150 to 300 units of BoNT-A were injected into the neck and shoulder muscles based on pain localization. Subjects completed the visual analog scale (VAS), Pain Frequency Questionnaire and the Modified Oswestry Pain Questionnaire (MOPQ) at baseline, 3 and 8 weeks after the treatment. The primary outcomes consisted of: 1) >= 50% improvement on the VAS; and 2) >= 30% reduction in pain day frequency. The secondary outcome was an improvement of ADL in MOPQ. Excellent responders (ERs) were those who met all three outcomes. Results. At 2 months, a significant reduction in the mean VAS (pain intensity) was noted in the BoNT-A group compared with the placebo (P = 0.0018, CI 95% from 2.51 to 7.89). At 2 months, there were six ERs in the BoNT-A group and one ER in the placebo group (P = 0.0152). Conclusion. Administration of BoNT-A into the neck and shoulder muscles for treatment of chronic refractory neck pain met one of the two primary outcomes: reduction in pain intensity. More ERs were noted in the Botox group. C1 [Miller, Diana; Richardson, Diana; Jabbari, Bahman] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Eisa, Mahmood] Neurol Neurosurg Spine Ctr, Valdosta, GA USA. [Bajwa, Rizma Jalees] James J Peters VA Med Ctr, Bronx, NY USA. RP Miller, D (reprint author), Yale Univ, Sch Med, Dept Neurol, Temple Med Bldg,40 Temple St,Suite 6C, New Haven, CT 06510 USA. EM diana.miller@yale.edu NR 24 TC 13 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD SEP PY 2009 VL 10 IS 6 BP 1012 EP 1017 DI 10.1111/j.1526-4637.2009.00658.x PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 495PU UT WOS:000269906800008 PM 19594841 ER PT J AU Manchikanti, L Datta, S Smith, HS Hirsch, JA AF Manchikanti, Laxmaiah Datta, Sukdeb Smith, Howard S. Hirsch, Joshua A. TI Evidence-Based Medicine, Systematic Reviews, and Guidelines in Interventional Pain Management: Part 6. Systematic Reviews and Meta-Analyses of Observational Studies SO PAIN PHYSICIAN LA English DT Review DE Observational studies; evidence-based medicine; systematic reviews; meta-analysis; randomized trials; case-control studies; cross-sectional studies; cohort studies; confounding bias; QUOROM; MOOSE ID LOW-BACK-PAIN; RANDOMIZED CONTROLLED-TRIALS; VERTEBRAL COMPRESSION FRACTURES; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SPINAL-CORD STIMULATION; EPIDEMIOLOGY STROBE STATEMENT; EPIDURAL STEROID INJECTIONS; HEALTH-CARE INTERVENTIONS; FACET JOINT INTERVENTIONS; LUMBAR SURGERY SYNDROME AB Observational studies provide an important source of information when randomized controlled trials (RCTs) cannot or should not be undertaken, provided that the data are analyzed and interpreted with special attention to bias. Evidence-based medicine (EBM) stresses the examination of evidence from clinical research and describes it as a shift in medical paradigm, in contrast to intuition, unsystematic clinical experience, and pathophysiologic rationale. While the importance of randomized trials has been created by the concept of the hierarchy of evidence in guiding therapy, much of the medical research is observational. The reporting of observational research is often not detailed and clear enough with insufficient quality and poor reporting, which hampers the assessment of strengths and weaknesses of the study and the generalizability of the mixed results. Thus, in recent years, progress and innovations in health care are measured by systematic reviews and meta-analyses. A systematic review is defined as, "the application of scientific strategies that limit bias by the systematic assembly, clinical appraisal, and synthesis of all relevant studies on a specific topic." Meta-analysis usually is the final step in a systematic review. Systematic reviews and meta-analyses are labor intensive, requiring expertise in both the subject matter and review methodology, and also must follow the rules of EBM which suggests that a formal set of rules must complement medical training and common sense for clinicians to integrate the results of clinical research effectively. While expertise in the review methods is important, the expertise in the subject matter and technical components is also crucial. Even though, systematic reviews and meta-analyses, specifically of RCTs, have exploded, the quality of the systematic reviews is highly variable and consequently, the opinions reached of the same studies are quite divergent. Numerous deficiencies have been described in methodologic assessment of the quality of the individual articles. Consequently, observational studies can provide an important complementary source of information, provided that the data are analyzed and interpreted in the context of confounding bias to which they are prone. Appropriate systematic reviews of observational studies, in conjunction with RCTs, may provide the basis for elimination of a dangerous discrepancy between the experts and the evidence. Steps in conducting systematic reviews of observational studies include planning, conducting, reporting, and disseminating the results. MOOSE, or Meta-analysis of Observational Studies in Epidemiology, a proposal for reporting contains specifications including background, search strategy, methods, results, discussion, and conclusion. Use of the MOOSE checklist should improve the usefulness of meta-analysis for authors, reviewers, editors, readers, and decision-makers. This manuscript describes systematic reviews and meta-analyses of observational studies. Authors frequently utilize RCTs and observational studies in one systematic review; thus, they should also follow the reporting standards of the Quality of Reporting of Meta-analysis (QUOROM) statement, which also provides a checklist. A combined approach of QUOROM and MOOSE will improve reporting of systematic reviews and lead to progress and innovations in health care. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Datta, Sukdeb] Vanderbilt Univ, Med Ctr, Intervent Pain Program, Nashville, TN USA. [Datta, Sukdeb] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA. [Smith, Howard S.] Albany Med Coll, Dept Anesthesiol, Albany, NY 12208 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU Sucampo Pharmaceuticals FX Conflict of Interest: Dr. Datta receives research support from Sucampo Pharmaceuticals and an honorarium from Smith and Nephew. NR 292 TC 83 Z9 84 U1 1 U2 10 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD SEP-OCT PY 2009 VL 12 IS 5 BP 819 EP 850 PG 32 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 508JN UT WOS:000270926900002 PM 19787009 ER PT J AU Hirsch, AE Rosenstein, BS Medich, DC Martel, CB Hirsch, JA AF Hirsch, Ariel E. Rosenstein, Barry S. Medich, David C. Martel, Christopher B. Hirsch, Joshua A. TI Polymethylmethacrylate and Radioisotopes in Vertebral Augmentation: An Explanation of Underlying Principles SO PAIN PHYSICIAN LA English DT Review DE polymethylmethacrylate; radioisotopes; vertebral; augmentation; Monte Carlo; biologically; effective; dose ID COMPRESSION FRACTURES; DOSE FRACTIONATION; HYPOFRACTIONATION; RADIOTHERAPY; RESPONSES; CANCER AB We recently reported a novel concept for combining radioactive isotope technology with polymethylmethacrylate (PMMA) cement used for vertebral augmentation and have advocated that pain physicians become aware of this new concept when treating malignant compression fractures. The use of vertebral augmentation for malignant compression fractures is steadily increasing, and the goal of this novel approach would be to stabilize the fractured vertebral body while also controlling proliferation of the tumor cells in the vertebral body that caused the vertebral fracture. This approach would therefore provide mechanical stabilization of the fractured vertebral body at the same time as direct targeting of the cancer cells causing the fracture. For our analysis, we investigated six specific radioisotopes with regard to physical and biologic properties as they would interact with PMMA and local bone metastatic disease, taking into consideration anatomical, biological and physical characteristics. The radioisotopes investigated include beta emitting (plus and minus) sources, as well as low energy and mid-energy photon sources and are: P-32, Ho-166, Y-90, I-125, F-18, and Tc-99m. We review the advantages and disadvantages of each radioisotope. In addition, this paper serves to provide pain physicians with a basic background of the biologic principles (Biologically Effective Dose) and statistical modeling (Monte Carlo method) used in that analysis. We also review the potential complications when using radioactive sources in a clinical setting. Understanding the methodologies employed in determining isotope selection empowers the practitioner by fostering understanding of this presently theoretical treatment option. We believe that embedding radioisotopes in PMMA is merely a first step in the road of local treatment for symptomatic local lesions in the setting of systemic disease. C1 [Hirsch, Ariel E.] Boston Univ, Massachusetts Gen Hosp, Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA. [Rosenstein, Barry S.] Mt Sinai Sch Med, Dept Radiat Oncol, New York, NY USA. [Rosenstein, Barry S.] Mt Sinai Sch Med, Dept Dermatol, New York, NY USA. [Rosenstein, Barry S.] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA. [Rosenstein, Barry S.] NYU, Sch Med, Dept Radiat Oncol, New York, NY USA. [Medich, David C.] Univ Massachusetts, Radiat Lab, Lowell, MA USA. [Martel, Christopher B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Div Intervent Neuroradiol, Dept Radiol, Boston, MA 02114 USA. RP Hirsch, AE (reprint author), Boston Univ, Massachusetts Gen Hosp, Med Ctr, Dept Radiat Oncol, 830 Harrison Ave,Moakley Bldg LL, Boston, MA 02118 USA. EM Ariel.hirsch@bmc.org NR 15 TC 8 Z9 8 U1 0 U2 2 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD SEP-OCT PY 2009 VL 12 IS 5 BP 887 EP 891 PG 5 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 508JN UT WOS:000270926900008 PM 19787015 ER PT J AU Herrington, B Kieran, MW AF Herrington, Betty Kieran, Mark W. TI Small Molecule Inhibitors in Children With Malignant Gliomas SO PEDIATRIC BLOOD & CANCER LA English DT Review DE angiogenesis; cell signaling; glioma; small molecule inhibitor; targeted therapy ID HIGH-GRADE ASTROCYTOMA; BRAIN-STEM GLIOMA; GLIOBLASTOMA-MULTIFORME; PEDIATRIC GLIOBLASTOMA; TARGETED THERAPIES; NERVOUS-SYSTEM; PHASE-I; TUMORS; CHEMOTHERAPY; CANCER AB Pediatric high grade gliomas (HGG) remain difficult to cure despite recent advances in imaging, neurosurgery, and radiation. Current treatment modalities have demonstrated only modest survival benefit. Research utilizing molecular biologic techniques reveals that the phenotype of HGG is complex and results from dysregulation of numerous inter-related cellular pathways. Knowledge of potential molecular targets along dysregulated pathways has led to the development of novel and highly specific targeted therapies, which include small molecule inhibitors. This article will review small molecule inhibition of cellular pathways involved in gliomagenesis, challenges to small molecule therapy, and future directions in the use of this therapy. Pediatr Blood Cancer 2009;53:312-317. (C) 2009 Wiley-Liss, Inc. C1 [Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Kieran, MW (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,SW331, Boston, MA 02115 USA. EM mark_kieran@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 45 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2009 VL 53 IS 3 BP 312 EP 317 DI 10.1002/pbc.21950 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 476LT UT WOS:000268443200005 PM 19434732 ER PT J AU Manley, P Li, XC Turner, C Chi, S Zimmerman, MA Chordas, C Gordon, A Baker, A Ullrich, NJ Goumnerova, L Marcus, K Hoffman, K Kieran, MW AF Manley, Peter Li, Xiaochun Turner, Christopher Chi, Susan Zimmerman, Mary Ann Chordas, Christine Gordon, Amanda Baker, Amanda Ullrich, Nicole J. Goumnerova, Liliana Marcus, Karen Hoffman, Ken Kieran, Mark W. TI A Prospective, Blinded Analysis of A-PROTEIN (Recoverin or CAR Protein) Levels in Pediatric Patients With Central Nervous System Tumors SO PEDIATRIC BLOOD & CANCER LA English DT Article DE A-PROTEIN; brain tumor; CAR; pediatric; recoverin; surrogate marker ID CANCER-ASSOCIATED RETINOPATHY; PARANEOPLASTIC ANTIGEN; ABERRANT EXPRESSION; LUNG-CANCER; CELL-LINES; MARKERS AB Background. Abnormal expression of A-PROTEIN has been identified in a number Of tumors including carcinoma of the lung, breast, colon, prostate, and cervix. Brain tumors have been reported to express high plasma levels of A-PROTEIN, Suggesting that it may be of significant diagnostic and prognostic value. Procedure. This prospective study evaluated the sensitivity and specificity of A-PROTEIN levels in pediatric brain tumor patients, Patients included those with newly diagnosed disease pre- and post-surgery, during treatment, during routine follow-up, and at recurrence or progression. A total of 154 A-PROTEIN levels from 54 patients were evaluated. Results. For patients without evidence of disease, 42% had normal A-PROTEIN levels, 35% were elevated, and 23% were equivocal. For patients with stable disease, 53% demonstrated normal A-PROTEIN levels, 19% were elevated, and 28% were equivocal. For patients with progressive disease, 53% had normal A-PROTEIN levels, 35% were elevated, and 12% were equivocal. The sensitivity was 35% and the specificity was 50%. A correlation of increased A-PROTEIN levels in patients with increased disease in glial tumors was also identified. Conclusions. A-PROTEIN levels were not predictive of disease status in children with most brain tumors. However, in patients with glial tumors there was a correlation with increased disease and elevated A-PROTEIN levels. This Could represent variability of A-PROTEIN during growth, development, or tumor cell origin and needs further evaluation. Pediatr Blood Cancer 2009;53:343-347. (C) 2009 Wiley-Liss, Inc. C1 [Manley, Peter; Turner, Christopher; Chi, Susan; Zimmerman, Mary Ann; Chordas, Christine; Gordon, Amanda; Baker, Amanda; Kieran, Mark W.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Manley, Peter] Hasbro Childrens Hosp, Dept Pediat Hematol Oncol, Providence, RI USA. [Li, Xiaochun] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Ullrich, Nicole J.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Goumnerova, Liliana] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Marcus, Karen] Childrens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Hoffman, Ken] Cytra Corp, Wrentham, MA USA. RP Kieran, MW (reprint author), Dana Farber Canc Inst, Dept Pediat Neurooncol, 44 Binney St,Room SW331, Boston, MA 02115 USA. EM mark_kieran@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU Stop&Shop Pediatric Brain Tumor Program; CJ Buckley Brain Tumor Research Fund FX Grant sponsor: Stop&Shop Pediatric Brain Tumor Program; Grant sponsor: CJ Buckley Brain Tumor Research Fund. NR 19 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2009 VL 53 IS 3 BP 343 EP 347 DI 10.1002/pbc.22017 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 476LT UT WOS:000268443200011 PM 19422022 ER PT J AU Turner, CD Chordas, CA Liptak, CC Rey-Casserly, C Delaney, BL Ullrich, NJ Goumnerova, LC Scott, RM Begley, HC Fletcher, WJ Yao, XP Chi, S Kieran, MW AF Turner, Christopher D. Chordas, Christine A. Liptak, Cori C. Rey-Casserly, Celiane Delaney, Brian L. Ullrich, Nicole J. Goumnerova, Liliana C. Scott, R. Michael Begley, Heather C. Fletcher, William J. Yao, Xiaopan Chi, Susan Kieran, Mark W. TI Medical, Psychological, Cognitive and Educational Late-Effects in Pediatric Low-Grade Glioma Survivors Treated With Surgery Only SO PEDIATRIC BLOOD & CANCER LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol DE gliomas; late effects of cancer treatment; low-grade; neuro-oncology; outcomes research; psychosocial; quality of life ID CHILDHOOD-CANCER SURVIVOR; LONG-TERM SURVIVORS; BRAIN-TUMORS; RETROSPECTIVE ANALYSIS; ADULT SURVIVORS; CHILDREN; ASTROCYTOMA; SEQUELAE; ADJUSTMENT AB Background. Surgical resection is often the only treatment necessary for pediatric low-grade gliomas (LGGs) and is thought to define a population with an excellent long-term prognosis. The goal Of this study was to describe the Multidimensional late-effects of pediatric LGG survivors treated exclusively with surgery. Methods. A retrospective chart review Of "surgery-only" LGG Survivors followed at Dana-Farber/Children's Hospital Cancer Care was undertaken. Patients had to be diagnosed with an LGG before the age of 22 years, treated with "surgery-only" and be at least 2 years from diagnosis. Results. Sixty survivors were eligible with a median age at the time of review of 16.3 years and the median time since diagnosis of 8.4 years. Turner locations were predominantly posterior fossa (47%) or cortical (33%). Eighty-five percent of patients had at least one ongoing late-effect, and 289% had three or more. The most common late-effects consisted of motor dysfunction (43%), Visual problems (321%), anxiety (19%), social difficulties (19%), seizure disorders (17%), depression (15%), poor coordination/ataxia (14%), behavioral problems (13%), and endocrinopathies (10%). Nine patients had a history Of Suicidal ideation; two with Suicide attempts. The mean full-scale IQ was normal, however, the number Of Survivors scoring one standard deviation below the mean was twice the expected number. Special education services were utilized by more than half of the Survivors. Conclusions. "Surgery-only" LGG Survivors may be more affected by their turner and its resection than previously appreciated. A prospective Study is needed to address this Survivor population. Pediatr Blood Cancer 2009;53:417-423. (C) 2009 Wiley-Liss, Inc. C1 [Turner, Christopher D.; Chordas, Christine A.; Rey-Casserly, Celiane; Ullrich, Nicole J.; Fletcher, William J.; Chi, Susan; Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Turner, Christopher D.; Chi, Susan; Kieran, Mark W.] Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. [Liptak, Cori C.; Delaney, Brian L.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Liptak, Cori C.; Rey-Casserly, Celiane; Delaney, Brian L.] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Ullrich, Nicole J.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Goumnerova, Liliana C.; Scott, R. Michael] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Begley, Heather C.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Yao, Xiaopan] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Turner, CD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,SW 331, Boston, MA 02115 USA. EM christopher_turner@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 26 TC 22 Z9 22 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2009 VL 53 IS 3 BP 417 EP 423 DI 10.1002/pbc.22081 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 476LT UT WOS:000268443200025 PM 19479971 ER PT J AU Typpo, KV Petersen, NJ Hallman, M Markovitz, BP Mariscalco, M AF Typpo, Katri V. Petersen, Nancy J. Hallman, Michael Markovitz, Barry P. Mariscalco, Michele TI Day 1 multiple organ dysfunction syndrome is associated with poor functional outcome and mortality in the pediatric intensive care unit SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE multiple organ failure; pediatric; intensive care; critical care; outcomes research; epidemiology ID CRITICALLY-ILL CHILDREN; SYSTEM FAILURE; SEVERE SEPSIS; PELOD SCORE; EPIDEMIOLOGY; RISK; IMPLEMENTATION; HYPERGLYCEMIA; MULTICENTER; PREDICTORS AB Objective. The epidemiology and outcomes of multiple organ dysfunction syndrome (MODS) are incompletely characterized in the pediatric population due to small sample size and conflicting diagnoses of organ failure. We sought to describe the epidemiology and outcomes of early MODS in a large clinical database of pediatric intensive care unit (PICU) patients based on consensus definitions of organ failure. Design. Retrospective analysis of a contemporaneously collected clinical PICU database. Setting: Virtual Pediatric Intensive Care Unit Performance System database patient admissions from January 2004 to December 2005 for 35 U.S. children's hospitals. Patients. We evaluated 63,285 consecutive PICU admissions from January 2004 to December 2005 in the Virtual Pediatric Intensive Care Unit Performance System database. We excluded patients younger than 1 month or older than 18 years of age, and hospitals with >10% missing values for MODS variables. We identified day 1 MODS by International Pediatric Sepsis Consensus Conference criteria with day I laboratory and vital sign values. We evaluated functional status using Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores from PICU admission and discharge. Interventions: Analysis: Student's t test, chi-square test Mann-Whitney rank sum, Kruskal-Wallis, and linear and logistic regression. Measurements and Main Results. We analyzed 44,693 admissions from 28 hospitals meeting inclusion criteria. Overall PICU mortality was 2.8%. We identified day 1 MODS in 18.6% of admissions. Patients with day 1 MODS had higher mortality (10.0% vs. 1.2%, p < .001), longer PICU length of stay (3.6 vs. 1.3 days, p < .001), and larger change from baseline Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores at time of PICU discharge (p < .001). Infants had the highest incidence of day 1 MODS (25.2% vs. 16.5%, p < .001) compared with other age groups. Conclusions. Using the largest clinical dataset to date and consensus definitions for organ failure, we found that children with MODS present on day 1 of intensive care unit admission have worse functional outcomes, higher mortality, and longer PICU length of stay than children who do not have MODS on day 1. Infants are disproportionally affected by MODS. (Pediatr Crit Care Med 2009; 10:562-570) C1 [Typpo, Katri V.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Baylor Coll Med, Houston, TX USA. [Hallman, Michael] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Markovitz, Barry P.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Markovitz, Barry P.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA. [Mariscalco, Michele] Baylor Coll Med, Dept Pediat, Sect Crit Care Med, Houston, TX 77030 USA. RP Typpo, KV (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Baylor Coll Med, Houston, TX USA. EM marym@bcm.tmc.edu FU NIH [T32HL007939]; American Thoracic Society [ATS F-07-014] FX Supported, in part, by grant NIH T32HL007939 (KVT) and American Thoracic Society Fellow's Career Development Award ATS F-07-014 (KVT). NR 37 TC 30 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD SEP PY 2009 VL 10 IS 5 BP 562 EP 570 DI 10.1097/PCC.0b013e3181a64be1 PG 9 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 496HF UT WOS:000269959900005 PM 19741445 ER PT J AU Brink, S Laffel, L Likitmaskul, S Liu, L Maguire, AM Olsen, B Silink, M Hanas, R AF Brink, Stu Laffel, Lori Likitmaskul, Supawadee Liu, Li Maguire, Ann M. Olsen, Birthe Silink, Martin Hanas, Ragnar TI Sick day management in children and adolescents with diabetes SO PEDIATRIC DIABETES LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; REDUCES HOSPITAL VISITS; DOSE GLUCAGON RESCUE; TYPE-1; KETOACIDOSIS; HYPOGLYCEMIA; MELLITUS; KETONES; T1DM C1 [Brink, Stu] Tufts Univ, Sch Med, Dept Pediat, Boston, MA 02111 USA. [Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Likitmaskul, Supawadee] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Pediat, Bangkok 10700, Thailand. [Liu, Li] Guangzhou Children Hosp, Dept Endocrinol & Metab, Guangzhou, Guangdong, Peoples R China. [Maguire, Ann M.; Silink, Martin] Childrens Hosp Westmead, Sydney, NSW, Australia. [Maguire, Ann M.; Silink, Martin] Univ Sydney, Sydney, NSW 2006, Australia. [Olsen, Birthe] Glostrup Univ Hosp, Dept Pediat, Copenhagen, Denmark. [Hanas, Ragnar] Uddevalla Cent Hosp, Dept Pediat, Uddevalla, Sweden. RP Brink, S (reprint author), New England Diabet & Endocrinol Ctr, Waltham, MA 02451 USA. EM stubrink@aol.com NR 24 TC 12 Z9 12 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD SEP PY 2009 VL 10 BP 146 EP 153 DI 10.1111/j.1399-5448.2009.00581.x PG 8 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 496ON UT WOS:000269984200014 PM 19754625 ER PT J AU Karsli, T Kalra, MK Self, JL Rosenfeld, JA Butler, S Simoneaux, S AF Karsli, Tijen Kalra, Mannudeep K. Self, Julie L. Rosenfeld, Jason Anders Butler, Susan Simoneaux, Stephen TI What physicians think about the need for informed consent for communicating the risk of cancer from low-dose radiation SO PEDIATRIC RADIOLOGY LA English DT Article DE Radiation; Cancer; Consent; Survey; Children ID DIAGNOSTIC CT SCANS; EXPOSURE; PATIENT AB The National Institute of Environmental Health Sciences, a subsidiary of the Food and Drug Administration, has declared that X-ray radiation at low doses is a human carcinogen. The purpose of our study was to determine if informed consent should be obtained for communicating the risk of radiation-induced cancer from radiation-based imaging. Institutional review board approval was obtained for the prospective survey of 456 physicians affiliated with three tertiary hospitals by means of a written questionnaire. Physicians were asked to state their subspecialty, number of years in practice, frequency of referral for CT scanning, level of awareness about the risk of radiation-induced cancer associated with CT, knowledge of whether such information is provided to patients undergoing CT, and opinions about the need for obtaining informed consent as well as who should provide information about the radiation-induced cancer risk to patients. Physicians were also asked to specify their preference among different formats of informed consent for communicating the potential risk of radiation-induced cancer. Statistical analyses were performed using the chi-squared test. Most physicians stated that informed consent should be obtained from patients undergoing radiation-based imaging (71.3%, 325/456) and the radiology department should provide information about the risk of radiation-induced cancer to these patients (54.6%, 249/456). The informed consent format that most physicians agreed with included modifications to the National Institute of Environmental Health Services report on cancer risk from low-dose radiation (20.2%, 92/456) or included information on the risk of cancer from background radiation compared to that from low-dose radiation (39.5%, 180/456). Most physicians do not know if patients are informed about cancer risk from radiation-based imaging in their institutions. However, they believe that informed consent for communicating the risk of radiation-induced cancer should be obtained from patients undergoing radiation-based imaging. C1 [Kalra, Mannudeep K.; Simoneaux, Stephen] Childrens Healthcare Atlanta, Dept Radiol, Atlanta, GA USA. [Self, Julie L.; Rosenfeld, Jason Anders; Butler, Susan] Emory Univ & Affiliates, Dept Behav Sci & Hlth Educ, Atlanta, GA USA. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St, Boston, MA 02114 USA. EM mkalra@partners.org NR 18 TC 23 Z9 23 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD SEP PY 2009 VL 39 IS 9 BP 917 EP 925 DI 10.1007/s00247-009-1307-5 PG 9 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 484PS UT WOS:000269059700003 PM 19557405 ER PT J AU Hussaini, BE Treanor, PR Healey, NA Tilahun, D Srey, R Lu, XG Khuri, SF Thatte, HS AF Hussaini, Bader E. Treanor, Patrick R. Healey, Nancy A. Tilahun, Daniel Srey, Rithy Lu, Xiu-Gui Khuri, Shukri F. Thatte, Hemant S. TI Evaluation of blood components exposed to coated arterial filters in extracorporeal circuits SO PERFUSION-UK LA English DT Article DE extracorporeal circulation; arterial filters; hemocompatibility; heparin-bonded circuit; blood component ID CARDIOPULMONARY BYPASS CIRCUITS; SYSTEMIC INFLAMMATORY RESPONSE; COMPLEMENT ACTIVATION; SAPHENOUS-VEIN; LEUKOCYTE DEPLETION; BIOCOMPATIBILITY; INJURY; DAMAGE; LUNG AB Background: Biocompatible surfaces play an important role in the inflammatory response during cardiopulmonary bypass (CBP), with the arterial filter contributing a large surface area of the circuit. Different filter-coating materials designed to improve blood-filter biocompatibility are currently used in CPB circuits. This study evaluates eight biocompatible coatings used for arterial filters and their effects on blood components during circulation. Methods: Arterial filters were randomly assigned in eight independent heparin-bonded tubing loops and perfused by a single swine (n=8). Arterial blood was routed simultaneously, but separately, into each circuit and circulated for 30 minutes at 37 degrees C. Blood samples were drawn for CBC, ACT, and TAT III measurements at baseline, post-heparinization and post-circulation. At study completion, filters were imaged using multiphoton microscopy. Results: RBC, platelet, and WBC counts, and TAT III complex were all decreased after 30 minutes of circulation; however, WBC count was the only parameter that showed statistically significant differences between the filters. Circulating WBC reduction ranged from 6% (Carmeda and Trillium) to 41% (Terumo-X-coating) with corresponding microscopic confirmation of increased WBC entrapment. Conclusion: All eight filter coatings altered the blood components to varying degrees. Selection of the most effective filter, in conjunction with a heparin-bonded circuit for CPB, may decrease the intraoperative foreign-surface activation of blood cells. C1 [Hussaini, Bader E.; Treanor, Patrick R.; Healey, Nancy A.; Tilahun, Daniel; Srey, Rithy; Lu, Xiu-Gui; Khuri, Shukri F.; Thatte, Hemant S.] VA Boston Healthcare Syst, Dept Surg, Cardiothorac Div, W Roxbury, MA 02132 USA. [Hussaini, Bader E.; Lu, Xiu-Gui; Khuri, Shukri F.; Thatte, Hemant S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hussaini, Bader E.; Lu, Xiu-Gui; Khuri, Shukri F.; Thatte, Hemant S.] Harvard Univ, Sch Med, Boston, MA USA. RP Thatte, HS (reprint author), VA Boston Healthcare Syst, Dept Surg MC112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Hemant_thatte@hms.harvard.edu FU Gish Medical (Gish Biomedical, INC. Rancho Santa Margarita, CA); Medtronic, Inc.(Minneapolis, MN); DOD/Office of Naval Research "ONR"; Richard Warren Surgical Research and Educational Fund, Westwood, MA FX This work was supported by funding from Gish Medical (Gish Biomedical, INC. Rancho Santa Margarita, CA), Medtronic, Inc.(Minneapolis, MN) (PT), DOD/Office of Naval Research "ONR" (HST), and the Richard Warren Surgical Research and Educational Fund, Westwood, MA. (SFK & HST) NR 26 TC 12 Z9 15 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0267-6591 J9 PERFUSION-UK JI Perfusion-UK PD SEP PY 2009 VL 24 IS 5 BP 317 EP 323 DI 10.1177/0267659109353818 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 539IG UT WOS:000273247000004 PM 19965951 ER PT J AU Hothi, SS Thomas, G Killeen, MJ Grace, AA Huang, CLH AF Hothi, Sandeep S. Thomas, Glyn Killeen, Matthew J. Grace, Andrew A. Huang, Christopher L. -H. TI Empirical correlation of triggered activity and spatial and temporal re-entrant substrates with arrhythmogenicity in a murine model for Jervell and Lange-Nielsen syndrome SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE Mice; Action potential duration; Ventricular arrhythmogenesis; Re-entry ID LONG-QT SYNDROME; ACTION-POTENTIAL DURATION; 2-NICOTINAMIDETHYL NITRATE SG-75; POTASSIUM CHANNEL OPENERS; CARDIAC PURKINJE FIBRES; VENTRICULAR ARRHYTHMOGENESIS; TARGETED DISRUPTION; SUDDEN-DEATH; K+ CHANNEL; EARLY AFTERDEPOLARIZATIONS AB KCNE1 encodes the beta-subunit of the slow component of the delayed rectifier K(+) current. The Jervell and Lange-Nielsen syndrome is characterized by sensorineural deafness, prolonged QT intervals, and ventricular arrhythmogenicity. Loss-of-function mutations in KCNE1 are implicated in the JLN2 subtype. We recorded left ventricular epicardial and endocardial monophasic action potentials (MAPs) in intact, Langendorff-perfused mouse hearts. KCNE1 (-/-) but not wild-type (WT) hearts showed not only triggered activity and spontaneous ventricular tachycardia (VT), but also VT provoked by programmed electrical stimulation. The presence or absence of VT was related to the following set of criteria for re-entrant excitation for the first time in KCNE1 (-/-) hearts: Quantification of APD(90), the MAP duration at 90% repolarization, demonstrated alterations in (1) the difference, a dagger APD(90), between endocardial and epicardial APD(90) and (2) critical intervals for local re-excitation, given by differences between APD(90) and ventricular effective refractory period, reflecting spatial re-entrant substrate. Temporal re-entrant substrate was reflected in (3) increased APD(90) alternans, through a range of pacing rates, and (4) steeper epicardial and endocardial APD(90) restitution curves determined with a dynamic pacing protocol. (5) Nicorandil (20 A mu M) rescued spontaneous and provoked arrhythmogenic phenomena in KCNE1 (-/-) hearts. WTs remained nonarrhythmogenic. Nicorandil correspondingly restored parameters representing re-entrant criteria in KCNE1 (-/-) hearts toward values found in untreated WTs. It shifted such values in WT hearts in similar directions. Together, these findings directly implicate triggered electrical activity and spatial and temporal re-entrant mechanisms in the arrhythmogenesis observed in KCNE1 (-/-) hearts. C1 [Hothi, Sandeep S.; Huang, Christopher L. -H.] Univ Cambridge, Physiol Lab, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England. [Thomas, Glyn; Grace, Andrew A.; Huang, Christopher L. -H.] Univ Cambridge, Dept Biochem, Sect Cardiovasc Biol, Cambridge CB2 1QW, England. [Killeen, Matthew J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. [Killeen, Matthew J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hothi, SS (reprint author), Univ Cambridge, Physiol Lab, Dept Physiol Dev & Neurosci, Downing St, Cambridge CB2 3EG, England. EM ssh26@cam.ac.uk FU Wellcome Trust; Medical Research Council; British Heart Foundation; Helen Kirkland Trust; Papworth Hospital, UK; Medical Research Council Capacity Building Studentship FX Funding was provided by the Wellcome Trust, Medical Research Council, British Heart Foundation, Helen Kirkland Trust, and Papworth Hospital, UK. SSH was supported by a Medical Research Council Capacity Building Studentship. MJK acknowledges the generous support of the Avrith Fund. Sandeep S. Hothi and Glyn Thomas have contributed equally to this work. NR 77 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD SEP PY 2009 VL 458 IS 5 BP 819 EP 835 DI 10.1007/s00424-009-0671-1 PG 17 WC Physiology SC Physiology GA 478JV UT WOS:000268584600001 PM 19430811 ER PT J AU Dai, T Huang, YY Hamblin, MR AF Dai, Tianhong Huang, Ying-Ying Hamblin, Michael R. TI Photodynamic therapy for localized infections-State of the art SO PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY LA English DT Review DE Photodynamic therapy; Photosensitizer; Localized infection; Bacteria; Virus; Fungus; Skin; Wound; Burn ID EXPERIMENTAL PERIODONTAL-DISEASE; TOPICAL 5-AMINOLEVULINIC ACID; RANDOMIZED CLINICAL-TRIAL; MYCOBACTERIUM-BOVIS BCG; GRAM-NEGATIVE BACTERIA; HERPES-SIMPLEX VIRUS; ACNE-VULGARIS; IN-VIVO; STAPHYLOCOCCUS-AUREUS; HELICOBACTER-PYLORI AB Photodynamic therapy (PDT) was discovered over 100 years ago by observing the killing of microorganisms when harmless dyes and visible light were combined in vitro. Since then it has primarily been developed as a treatment for cancer, ophthalmologic disorders and in dermatology. However, in recent years interest in the antimicrobial. effects of PDT has revived and it has been proposed as a therapy for a Large variety of localized infections. This revival of interest has largely been driven by the inexorable increase in drug resistance among many classes of pathogen. Advantages of PDT include equal killing effectiveness regardless of antibiotic resistance, and a tack of induction of PDT resistance. Disadvantages include the cessation of the antimicrobial effect when the light is turned off, and less than perfect selectivity for microbial cells over host tissue. This review will cover the use of PDT to kill or inactivate pathogens in ex vivo tissues and in biological materials such as blood. PDT has been successfully used to kill pathogens and even to save Life in several animal models of localized infections such as surface wounds, burns, oral sites, abscesses and the middle ear. A large number of clinical. studies of PDT for viral papillomatosis Lesions and for acne refer to its antimicrobial effect, but it is unclear how important this microbial killing is to the overall therapeutic outcome. PDT for periodontitis is a rapidly growing clinical application and other dental applications are under investigation. PDT is being clinically studied for other dermatological infections such as leishmaniasis and mycobacteria. Antimicrobial PDT will become more important in the future as antibiotic resistance is only expected to continue to increase. (C) 2009 Elsevier B.V. All rights reserved. C1 [Dai, Tianhong; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St,BAR414, 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 [RO1AI050875]; US Air Force MFEL [FA9550-04-1-0079]; Bullock-Wellman Postdoctoral Fellowship Award FX Research in the Hamblin laboratory is supported by the NIH (grant RO1AI050875) and the US Air Force MFEL program (contract FA9550-04-1-0079). T. Dai was supported by the Bullock-Wellman Postdoctoral Fellowship Award. NR 152 TC 228 Z9 236 U1 9 U2 79 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1572-1000 J9 PHOTODIAGN PHOTODYN JI Photodiagnosis Photodyn. Ther. PD SEP-DEC PY 2009 VL 6 IS 3-4 BP 170 EP 188 DI 10.1016/j.pdpdt.2009.10.008 PG 19 WC Oncology SC Oncology GA 534OZ UT WOS:000272908300005 PM 19932449 ER PT J AU Saffarian, S Cocucci, E Kirchhausen, T AF Saffarian, Saveez Cocucci, Emanuele Kirchhausen, Tomas TI Distinct Dynamics of Endocytic Clathrin-Coated Pits and Coated Plaques SO PLOS BIOLOGY LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; INTERACTING PROTEIN-1 HIP1; PLASMA-MEMBRANE; MAMMALIAN-CELLS; ARP2/3 COMPLEX; LIGHT-CHAINS; IN-VIVO; N-WASP; ACTIN; RECRUITMENT AB Clathrin is the scaffold of a conserved molecular machinery that has evolved to capture membrane patches, which then pinch off to become traffic carriers. These carriers are the principal vehicles of receptor-mediated endocytosis and are the major route of traffic from plasma membrane to endosomes. We report here the use of in vivo imaging data, obtained from spinning disk confocal and total internal reflection fluorescence microscopy, to distinguish between two modes of endocytic clathrin coat formation, which we designate as "coated pits" and "coated plaques." Coated pits are small, rapidly forming structures that deform the underlying membrane by progressive recruitment of clathrin, adaptors, and other regulatory proteins. They ultimately close off and bud inward to form coated vesicles. Coated plaques are longer-lived structures with larger and less sharply curved coats; their clathrin lattices do not close off, but instead move inward from the cell surface shortly before membrane fission. Local remodeling of actin filaments is essential for the formation, inward movement, and dissolution of plaques, but it is not required for normal formation and budding of coated pits in the cells we have studied. We conclude that there are at least two distinct modes of clathrin coat formation at the plasma membrane classical coated pits and coated plaques-and that these two assemblies interact quite differently with other intracellular structures. C1 [Saffarian, Saveez] Harvard Univ, Childrens Hosp, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Immune Dis Inst, Boston, MA USA. RP Saffarian, S (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu FU National Institutes of Health [GM075252]; NERCE [U54 A1057159]; American Heart Association FX This work has been supported by a National Institutes of Health grant GM075252 (TK), a NERCE grant U54 A1057159 (TK), and by an American Heart Association postdoctoral fellowship (SS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 134 Z9 134 U1 6 U2 25 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD SEP PY 2009 VL 7 IS 9 AR e1000191 DI 10.1371/journal.pbio.1000191 PG 18 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 507AF UT WOS:000270820800006 PM 19809571 ER PT J AU Ross, JS Mulvey, GK Hines, EM Nissen, SE Krumholz, HM AF Ross, Joseph S. Mulvey, Gregory K. Hines, Elizabeth M. Nissen, Steven E. Krumholz, Harlan M. TI Trial Publication after Registration in ClinicalTrials.Gov: A Cross-Sectional Analysis SO PLOS MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; OUTCOME REPORTING BIAS; CLINICAL-TRIALS; ANTIINFLAMMATORY DRUGS; EMPIRICAL-EVIDENCE; OSTEOARTHRITIS; EFFICACY; NABUMETONE; PROTOCOLS; COMMITTEE AB Background: ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication. Methods and Findings: We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n= 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p < 0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006). Conclusions: Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data elements, the potential for ClinicalTrials.gov to address selective publication of clinical trials will be limited. C1 [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. [Ross, Joseph S.] James J Peters VA Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY USA. [Ross, Joseph S.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Mulvey, Gregory K.; Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Hines, Elizabeth M.] Amherst Coll, Amherst, MA 01002 USA. [Nissen, Steven E.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Sect Cardiolovasc Med, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Epidemiol & Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT 06510 USA. RP Ross, JS (reprint author), Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. EM joseph.ross@mssm.edu FU National Institute on Aging [K08 AG032886]; American Federation of Aging Research; Department of Veterans Affairs Health Services Research and Development [TRP-02-149]; Hartford Foundation FX This project was not directly supported by any external grants or funds. JSR is currently supported by the National Institute on Aging (K08 AG032886) and by the American Federation of Aging Research through the Paul B. Beeson Career Development Award Program and had received support from the Department of Veterans Affairs Health Services Research and Development Service project no. TRP-02-149 and by the Hartford Foundation during earlier periods in which this work was being conducted. 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 American Federation of Aging Research, the Department of Veterans Affairs, and the Hartford Foundation had no role in the design or conduct of the study; collection, management, analysis or interpretation of the data; preparation, review or approval of the manuscript. NR 31 TC 160 Z9 160 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD SEP PY 2009 VL 6 IS 9 AR e1000144 DI 10.1371/journal.pmed.1000144 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 506ZH UT WOS:000270818100008 PM 19901971 ER PT J AU Goodman, DW Thase, ME AF Goodman, David W. Thase, Michael E. TI Recognizing ADHD in Adults with Comorbid Mood Disorders: Implications for Identification and Management SO POSTGRADUATE MEDICINE LA English DT Article DE ADHD; mood disorders; comorbidity; adults ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND TRIAL; OROS METHYLPHENIDATE; BIPOLAR DISORDER; PSYCHIATRIC COMORBIDITY; SURVEY REPLICATION; EXTENDED-RELEASE; DEPRESSION AB The objective of this study was to assist those in psychiatric clinical practice in the identification and management of attention-deficit/hyperactivity disorder (ADHD) in adults, with an emphasis on ADHD in the presence of comorbid mood disorders in adults. PubMed was searched to identify relevant studies and critical reviews published in English between 1988 and 2008 on the prevalence, persistence, and consequences of ADHD in adults. Additionally, relevant studies and critical reviews pertaining to the treatment of adults with ADHD and the relationships between ADHD and mood disorders with regard to overlapping symptom profiles, comorbidity, and treatment options were identified. The symptoms of ADHD persist into adulthood for a high proportion of children with this disorder. Among adults, the estimated prevalence of clinician-assessed ADHD in the general population is 4% to 5%. Untreated ADHD can adversely affect school and work achievements, diminish self-esteem, damage interpersonal relationships, and significantly reduce quality of life for adults. A significant proportion of adults with mood disorders have comorbid ADHD, and a significant proportion of adults with ADHD have comorbid mood disorders. Few reports have described the outcome of treatment of individuals with ADHD and concurrent mood disorders and no controlled trials were identified. Attention-deficit/hyperactivity disorder in adults can be identified despite resembling, or coexisting with, other psychiatric disorders. The complexities of comorbid psychiatric conditions require careful diagnostic prioritization when developing a comprehensive sequential treatment plan. The current research literature offers little clinical guidance for constructing treatment algorithms. C1 [Goodman, David W.] Adult Attent Deficit Disorder Ctr Maryland, Johns Hopkins Green Spring Stn, Lutherville Timonium, MD USA. [Goodman, David W.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Goodman, DW (reprint author), Johns Hopkins Green Spring Stn, 10751 Falls Rd,Suite 306, Baltimore, MD 21093 USA. EM dgoodma4@jhmi.edu FU Shire US, Inc FX Funding was provided by Shire US, Inc. The authors wish to thank Timothy Coffey, Rosa Real, and William Perlman, Excerpta Medica, Bridgewater, NJ, for their editorial assistance. NR 67 TC 15 Z9 15 U1 0 U2 4 PU JTE MULTIMEDIA PI BERWYN PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD SEP PY 2009 VL 121 IS 5 BP 20 EP 30 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 506TL UT WOS:000270799000003 PM 19820271 ER PT J AU Tice, JA Kerlikowske, K AF Tice, Jeffrey A. Kerlikowske, Karla TI Screening and Prevention of Breast Cancer in Primary Care SO PRIMARY CARE LA English DT Review DE Breast cancer screening; Breast cancer prevention; Mammography; Digital mammography; Breast magnetic resonance imaging; Chemoprevention; Risk assessment; Guidelines ID FIELD DIGITAL MAMMOGRAPHY; CARCINOMA IN-SITU; BODY-MASS INDEX; RECREATIONAL PHYSICAL-ACTIVITY; FALSE-POSITIVE MAMMOGRAMS; SURGICAL ADJUVANT BREAST; HIGH GENETIC RISK; RANDOMIZED CONTROLLED-TRIALS; ESTROGEN PLUS PROGESTIN; SWEDISH 2-COUNTY TRIAL AB Mammography remains the mainstay of breast cancer screening. There is little controversy that mammography reduces the risk of dying from breast cancer by about 23% among women between the ages of 50 and 69 years, although the harms associated with false-positive results and overdiagnosis limit the net benefit of mammography. Women in their 70s may have a small benefit from screening mammography, but overdiagnosis increases in this age group as do competing causes of death. While new data support a 16% reduction in breast cancer mortality for 40- to 49-year-old women after 10 years of screening, the net benefit is less compelling in part because of the lower incidence of breast cancer in this age group and because mammography is less sensitive and specific in women younger than 50 years. Digital mammography is more sensitive than film mammography in young women with similar specificity, but no improvements in breast cancer outcomes have been demonstrated. Magnetic resonance imaging may benefit the highest risk women. Randomized trials suggest that self-breast examination does more harm than good. Primary prevention with currently approved medications will have a negligible effect on breast cancer incidence. Public health efforts aimed at increasing mammography screening rates, promoting regular exercise in all women, maintaining a healthy weight, limiting alcohol intake, and limiting postmenopausal hormone therapy may help to continue the recent trend of lower breast cancer incidence and mortality among American women. C1 [Tice, Jeffrey A.] Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA. [Kerlikowske, Karla] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. RP Tice, JA (reprint author), Univ Calif San Francisco, Div Gen Internal Med, Dept Med, 1701 Divisadero St,Suite 554, San Francisco, CA 94143 USA. EM jeff.tice@ucsf.edu NR 202 TC 12 Z9 14 U1 2 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0095-4543 J9 PRIMARY CARE JI Primary Care PD SEP PY 2009 VL 36 IS 3 BP 533 EP + DI 10.1016/j.pop.2009.04.003 PG 28 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 485PL UT WOS:000269135800008 PM 19616154 ER PT J AU Berman, SD West, JC Danielian, PS Caron, AM Stone, JR Lees, JA AF Berman, Seth D. West, Julie C. Danielian, Paul S. Caron, Alicia M. Stone, James R. Lees, Jacqueline A. TI Mutation of p107 exacerbates the consequences of Rb loss in embryonic tissues and causes cardiac and blood vessel defects SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell cycle; heart; p107; retinoblastoma ID RETINOBLASTOMA PROTEIN; TUMOR-SUPPRESSOR; TARGETED DISRUPTION; GENE-FUNCTION; MICE; MOUSE; P130; DIFFERENTIATION; EXPRESSION; DELETION AB The retinoblastoma tumor-suppressor protein, pRb, is a member of the pocket protein family that includes p107 and p130. These proteins have well-defined roles in regulating entry into and exit from the cell cycle and also have cell cycle-independent roles in facilitating differentiation. Here we investigate the overlap between pocket protein's function during embryonic development by using conditional mutant alleles to generate Rb; p107 double-mutant embryos (DKOs) that develop in the absence of placental defects. These DKOs die between e13.5 and e14.5, much earlier than either the conditional Rb or the germline p107 single mutants, which survive to birth or are largely viable, respectively. Analyses of the e13.5 DKOs shows that p107 mutation exacerbates the phenotypes resulting from pRb loss in the central nervous system and lens, but not in the peripheral nervous system. In addition, these embryos exhibit novel phenotypes, including increased proliferation of blood vessel endothelial cells, and heart defects, including double-outlet right ventricle (DORV). The DORV is caused, at least in part, by a defect in blood vessel endothelial cells and/or heart mesenchymal cells. These findings demonstrate novel, overlapping functions for pRb and p107 in numerous murine tissues. C1 [Berman, Seth D.; West, Julie C.; Danielian, Paul S.; Caron, Alicia M.; Lees, Jacqueline A.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Stone, James R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lees, JA (reprint author), MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. EM jalees@mit.edu FU National Cancer Institute/National Institutes of Health [CA121921] FX We thank T. Jacks for the Rb+/c and p107+/- mice, R. Hynes for antibodies, R. Bronson for invaluable histopathologic analysis, and Lees laboratory members for helpful discussions. This work was supported by a National Cancer Institute/National Institutes of Health Grant CA121921 ( to J. A. L.). S. D. B. was a David H. Koch Graduate Fellow and J. A. L. is a Ludwig Scholar at MIT. NR 23 TC 16 Z9 16 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 2009 VL 106 IS 35 BP 14932 EP 14936 DI 10.1073/pnas.0902408106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490EM UT WOS:000269481000037 PM 19706423 ER PT J AU Lloyd, JC Banez, LL Aronson, WJ Terris, MK Presti, JC Amling, CL Kane, CJ Freedland, SJ AF Lloyd, J. C. Banez, L. L. Aronson, W. J. Terris, M. K. Presti, J. C., Jr. Amling, C. L. Kane, C. J. Freedland, S. J. TI Preoperative predictors of blood loss at the time of radical prostatectomy: results from the SEARCH database SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE prostate neoplasm; blood loss; obesity; prostate weight; prostatectomy ID BODY-MASS INDEX; RETROPUBIC PROSTATECTOMY; SINGLE-INSTITUTION; OUTCOMES; CANCER; VOLUME; SURGEON; OBESITY; WEIGHT; IMPACT AB The literature contains conflicting data on preoperative predictors of estimated blood loss (EBL) at radical retropubic prostatectomy (RRP). We sought to examine preoperative predictors of EBL at the time of RRP among patients from the SEARCH database to lend clarity to this issue. A total of 1154 patients were identified in the SEARCH database who underwent RRP between 1988 and 2008 and had EBL data available. We examined multiple preoperative factors for their ability to predict EBL using multivariate linear regression analysis. Median EBL was 900 ml (s.d. 1032). The 25th and 75th percentile for EBL were 600 and 1500 ml, respectively. EBL increased significantly with increasing body mass index (BMI) and increasing prostate size and decreased with more recent year of RRP (all P < 0.001). The mean-adjusted EBL in normal-weight men (BMI < 25 kg/m(2)) was 807 ml compared to 1067 ml among severely obese men (BMI >= 35 kg/m(2)). Predicted EBL for men with the smallest prostates (<20 g) was 721 ml, compared to 1326 ml for men with prostates >= 100 g. Finally, statistically significant differences between centers were observed, with mean- adjusted EBL ranging from 844 to 1094 ml. Both BMI and prostate size are predictors of increased EBL. Prostate size is of particular note, as a nearly twofold increased EBL was seen from the smallest (<20 g) to the largest prostates (>= 100 g). Over time, average EBL significantly decreased. Finally, significant differences in EBL were observed between centers. Patients with multiple risk factors should be forewarned they are at increased risk for higher EBL, which may translate into a greater need for blood transfusion. Prostate Cancer and Prostatic Diseases (2009) 12, 264-268; doi: 10.1038/pcan.2009.6; published online 24 March 2009 C1 [Lloyd, J. C.; Banez, L. L.; Freedland, S. J.] Duke Univ, Sch Med, Div Urol, Duke Prostate Ctr, Durham, NC 27710 USA. [Lloyd, J. C.; Banez, L. L.; Freedland, S. J.] Duke Univ, Sch Med, Div Urol Surg, Dept Surg & Pathol, Durham, NC 27710 USA. [Lloyd, J. C.; Banez, L. L.; Freedland, S. J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Aronson, W. J.] Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Los Angeles, CA USA. [Aronson, W. J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Terris, M. K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Terris, M. K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Presti, J. C., Jr.] Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. [Presti, J. C., Jr.] Vet Affairs Med Ctr, Urol Sect, Palo Alto, CA 94304 USA. [Amling, C. L.] Univ Alabama, Dept Urol, Birmingham, AL USA. [Kane, C. J.] Vet Affairs Med Ctr, Urol Sect, San Diego, CA 92161 USA. [Kane, C. J.] Univ Calif San Diego, Sch Med, Div Urol, San Diego, CA 92103 USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, Div Urol, Duke Prostate Ctr, Box 2626 DUMC, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU Department of Veterans Affairs, National Institute of Health [R01CA100938]; NIH Specialized Programs of Research Excellence [P50 CA92131-01A1]; Georgia Cancer Coalition; Department of Defense, Prostate Cancer Research Program; American Urological Association Foundation/Astellas Rising Star in Urology Award; US Army or the Department of Defense FX This study was supported by the Department of Veterans Affairs, National Institute of Health R01CA100938 (WJA), NIH Specialized Programs of Research Excellence Grant P50 CA92131-01A1 (WJA), the Georgia Cancer Coalition (MKT), the Department of Defense, Prostate Cancer Research Program, (LLB, SJF) and the American Urological Association Foundation/Astellas Rising Star in Urology Award (SJF). Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense. NR 20 TC 6 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD SEP PY 2009 VL 12 IS 3 BP 264 EP 268 DI 10.1038/pcan.2009.6 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 490FD UT WOS:000269483200009 PM 19322137 ER PT J AU Calhoun, EA Clemens, JQ Litwin, MS Walker-Corkery, E Markossian, T Kusek, JW McNaughton-Collins, M AF Calhoun, E. A. Clemens, J. Q. Litwin, M. S. Walker-Corkery, E. Markossian, T. Kusek, J. W. McNaughton-Collins, M. CA Chronic Prostatitis Collaborative TI Primary care physician practices in the diagnosis, treatment and management of men with chronic prostatitis/chronic pelvic pain syndrome SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE chronic prostatitis; primary care physicians; survey; practice patterns ID SYMPTOM INDEX; PREVALENCE; COMMUNITY; QUESTIONNAIRE; UROLOGISTS AB To describe practice patterns of primary care physicians (PCPs) for the diagnosis, treatment and management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), we surveyed 556 PCPs in Boston, Chicago, and Los Angeles (RR = 52%). Only 62% reported ever seeing a patient like the one described in the vignette. In all, 16% were ` not at all' familiar with CP/CPPS, and 48% were ` not at all' familiar with the National Institutes of Health classification scheme. PCPs reported practice patterns regarding CP/CPPS, which are not supported by evidence. Although studies suggest that CP/CPPS is common, many PCPs reported little or no familiarity, important knowledge deficits and limited experience in managing men with this syndrome. Prostate Cancer and Prostatic Diseases (2009) 12, 288-295; doi: 10.1038/pcan.2009.9; published online 7 April 2009 C1 [Walker-Corkery, E.; McNaughton-Collins, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gen Internal Med Div, Boston, MA 02114 USA. [Calhoun, E. A.; Markossian, T.] Univ Illinois, Sch Publ Hlth, Div Hlth Policy & Adm, Chicago, IL USA. [Clemens, J. Q.] Univ Michigan, Med Ctr, Dept Urol, Ann Arbor, MI USA. [Litwin, M. S.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Urol, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Litwin, M. S.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Kusek, J. W.] NIDDK, NIH, Bethesda, MD USA. RP McNaughton-Collins, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gen Internal Med Div, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM mmcnaughtoncollins@partners.org FU National Institutes of Health [U01 DK65187, DK 65277, DK 65257] FX The authors thank all the participating primary care physicians for making this study possible. This research was funded by Grants (U01 DK65187, DK 65277, and DK 65257) from the National Institutes of Health, which had no other role in the design or conduct of the study, or preparation of the manuscript. NR 27 TC 7 Z9 7 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD SEP PY 2009 VL 12 IS 3 BP 288 EP 295 DI 10.1038/pcan.2009.9 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 490FD UT WOS:000269483200014 PM 19350050 ER PT J AU Tabata, K Watanabe, M Naruishi, K Edamura, K Satoh, T Yang, G Fattah, EA Wang, J Goltsov, A Floryk, D Soni, SD Kadmon, D Thompson, TC AF Tabata, K. Watanabe, M. Naruishi, K. Edamura, K. Satoh, T. Yang, G. Fattah, E. Abdel Wang, J. Goltsov, A. Floryk, D. Soni, S. D. Kadmon, D. Thompson, T. C. TI Therapeutic effects of gelatin matrix-embedded IL-12 gene-modified macrophages in a mouse model of residual prostate cancer SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE adenoviral vectors; IL-12; matrix-embedded gene-modified cell therapy; residual prostate cancer model ID TUMOR-ASSOCIATED MACROPHAGES; RADICAL PROSTATECTOMY; INTERLEUKIN-12; PROGRESSION; METASTASIS; SURGERY; GROWTH; AGENT AB We evaluated the potential use of intraoperative gelatin matrix hemostatic sealant (GMHS; FloSeal; Baxter Healthcare) embedded with macrophages (M phi) transduced with murine interleukin (IL)-12 recombinant adenoviral vector (G/M phi/AdmIL-12) for prevention of recurrence of prostate cancer following radical prostatectomy. Application of G/M phi/AdmIL-12 resulted in significant suppression of tumor growth and spontaneous lung metastases, a statistically significant survival advantage of the G/M phi/AdmIL-12-treated animals, more efficient trafficking of M phi to lymph nodes draining from the prostate and generation of systemic natural killer cell activity and tumor-specific cytolytic T lymphocyte responses compared to the controls in a preclinical mouse model of residual prostate cancer. Our data recommend this treatment as a novel adjuvant for prevention of local recurrence of prostate cancer following radical prostatectomy. Prostate Cancer and Prostatic Diseases (2009) 12, 301-309; doi: 10.1038/pcan.2008.57; published online 23 December 2008 C1 [Tabata, K.; Watanabe, M.; Naruishi, K.; Edamura, K.; Satoh, T.; Yang, G.; Fattah, E. Abdel; Wang, J.; Goltsov, A.; Floryk, D.; Soni, S. D.; Kadmon, D.; Thompson, T. C.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Kadmon, D.; Thompson, T. C.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Thompson, T. C.] Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. [Thompson, T. C.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Thompson, TC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Unit 1374, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM timthomp@mdanderson.org NR 21 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD SEP PY 2009 VL 12 IS 3 BP 301 EP 309 DI 10.1038/pcan.2008.57 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 490FD UT WOS:000269483200016 PM 19104507 ER PT J AU Vernier, G Wang, J Jennings, LD Sun, J Fischer, A Song, LK Collier, RJ AF Vernier, Gregory Wang, Jie Jennings, Laura D. Sun, Jianjun Fischer, Audrey Song, Likai Collier, R. John TI Solubilization and characterization of the anthrax toxin pore in detergent micelles SO PROTEIN SCIENCE LA English DT Article DE prepore-to-pore conversion; protein-detergent complex; conformational changes; biophysical characterization ID PROTEIN SECONDARY STRUCTURE; OUTER-MEMBRANE PROTEIN; CIRCULAR-DICHROISM SPECTRA; PROTECTIVE ANTIGEN CHANNEL; ESCHERICHIA-COLI; LETHAL FACTOR; BETA-BARREL; PHENYLALANINE CLAMP; STRUCTURAL-ANALYSIS; TRANSMEMBRANE PORE AB Proteolytically activated Protective Antigen (PA) moiety of anthrax toxin self-associates to form a heptameric ring-shaped oligomer (the prepore). Acidic pH within the endosome converts the prepore to a pore that serves as a passageway for the toxin's enzymatic moieties to cross the endosomal membrane. Prepore is stable in solution under mildly basic conditions, and lowering the pH promotes a conformational transition to an insoluble pore-like state. N-tetradecylphosphocholine (FOS14) was the only detergent among 110 tested that prevented aggregation without dissociating the multimer into its constituent subunits. FOS14 maintained the heptamers as monodisperse, insertion-competent 440-kDa particles, which formed channels in planar phospholipid bilayers with the same unitary conductance and ability to translocate a model substrate protein as channels formed in the absence of detergent. Electron paramagnetic resonance analysis detected pore-like conformational changes within PA on solubilization with FOS14, and electron micrograph images of FOS14-solubilized pore showed an extended, mushroom-shaped structure. Circular dichroism measurements revealed an increase in a helix and a decrease in beta structure in pore formation. Spectral changes caused by a deletion mutation support the hypothesis that the 2 beta 2-2 beta 3 loop transforms into the transmembrane segment of the beta-barrel stem of the pore. Changes caused by selected point mutations indicate that the transition to a structure is dependent on residues of the luminal 2 beta 11-2 beta 12 loop that are known to affect pore formation. Stabilizing the PA pore in solution with FOS14 may facilitate further structural analysis and a more detailed understanding of the folding pathway by which the pore is formed. C1 [Vernier, Gregory; Wang, Jie; Jennings, Laura D.; Sun, Jianjun; Fischer, Audrey; Collier, R. John] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Song, Likai] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Song, Likai] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Collier, RJ (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, 200 Longwood Ave, Boston, MA 02115 USA. EM jcollier@hms.harvard.edu OI Collier, R John/0000-0002-2427-4239 FU NIH [Al022021, Al19807, Al057159]; Gates Foundation FX Grant sponsor: NIH; Grant numbers: Al022021, Al19807, Al057159; Grant sponsor: Gates Foundation (CAVD grant). NR 62 TC 12 Z9 12 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD SEP PY 2009 VL 18 IS 9 BP 1882 EP 1895 DI 10.1002/pro.199 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 490TP UT WOS:000269528400007 PM 19609933 ER PT J AU Kaplan, K Kottsieper, P Scott, J Salzer, M Solomon, P AF Kaplan, Katy Kottsieper, Petra Scott, Jeniece Salzer, Mark Solomon, Phyllis TI Adoption and Safe Families Act State Statutes Regarding Parents with Mental Illnesses: A Review and Targeted Intervention SO PSYCHIATRIC REHABILITATION JOURNAL LA English DT Article DE parenting; psychiatric disability; disability policy; stigma ID MOTHERS AB Topic: This paper describes an intervention targeting states that list a parental mental illness/disability as an "aggravated circumstance" under the Adoption and Safe Families Act Of 1997 (ASFA), resulting in reasonable efforts not required to reunify a family. Purpose: This paper delineates the results from our review of ASFA state statutes, the development of a model ASFA statute, and strategies to educate legislators and the public about the impact of discrimination that parents with mental illnesses encounter because of ASFA legislation with the intent of modifying state ASFA legislation. Sources Used: The following sources were used for this educational initiative: a literature review and a review of ASFA state statutes. Conclusions: Adoption of the model ASFA state statute is simply a first step in an effort to end the discrimination that parents with psychiatric disabilities face; additional efforts are also noted. C1 [Kaplan, Katy; Salzer, Mark; Solomon, Phyllis] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Salzer, Mark] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin 4, Philadelphia, PA USA. [Scott, Jeniece] Villanova Law Sch, Villanova, PA USA. [Kottsieper, Petra] Philadelphia Coll Osteopath Med, Philadelphia, PA USA. [Solomon, Phyllis] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Kaplan, K (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,CMHPSR 3rd Floor, Philadelphia, PA 19104 USA. EM katykap@mail.med.upenn.edu NR 7 TC 7 Z9 7 U1 1 U2 5 PU CENTER PSYCHIATRIC REHABILITATION PI BOSTON PA BOSTON UNIV, 930 COMMONWEALTH AVE, BOSTON, MA 02215 USA SN 1095-158X J9 PSYCHIATR REHABIL J JI Psychiatr. Rehabil. J. PD FAL PY 2009 VL 33 IS 2 BP 91 EP 94 DI 10.2975/33.2.2009.91.94 PG 4 WC Psychiatry; Rehabilitation SC Psychiatry; Rehabilitation GA 507JZ UT WOS:000270850700003 PM 19808203 ER PT J AU Freed, MC Yeager, DE Liu, X Gore, KL Engel, CC Magruder, KM AF Freed, Michael C. Yeager, Derik E. Liu, Xian Gore, Kristie L. Engel, Charles C. Magruder, Kathryn M. TI Preference-Weighted Health Status of PTSD Among Veterans: An Outcome for Cost-Effectiveness Analysis Using Clinical Data SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PRIMARY-CARE; UTILITY MEASURES; METAANALYSIS; SYMPTOMS; PHARMACOTHERAPY; AFGHANISTAN; PREVALENCE; VALIDATION; CHECKLIST AB Objective: Posttraumatic stress disorder (PTSD) is a highly prevalent, chronic, disabling but treatable condition. Preference-based measures (for example, health utilities) are recommended for and useful in cost-effectiveness analyses and for policy decisions because they reflect a population's valuation of the desirability of disease states. However, no such measures exist for PTSD. This study aimed to estimate preference-weighted health status associated with PTSD and common co-occurring mental disorders in a sample of veterans by transforming health-related quality-of-life data into preference-weighted health status scores (PWHS scores), develop a usable regression model to predict PWHS scores from other data sets, and compare preference-weighted health status of PTSD with that of another chronic disorder, chronic obstructive pulmonary disease (COPD). Methods: A secondary analysis was performed on data from a random sample of 808 veterans (79% male; 12% met criteria for PTSD) in four primary care clinics. Veterans responded to the PTSD Checklist (PCL), Clinician-Administered PTSD Scale, Mini-International Neuropsychiatric Interview, and Medical Outcomes Survey Short Form-36. Results: PWHS scores were .029 lower among veterans with PTSD compared with veterans without PTSD, all else being equal. However, scores depended on PTSD severity, when the analysis controlled for other model variables. Specifically, PWHS scores dropped by .004 with a 1-unit increase in PCL scores among veterans without PTSD. Among veterans with PTSD, the reduction was .002. PTSD was associated with lower preference-weighted health status than COPD. Conclusions: This is the first study to estimate preference-weighted health status of persons with PTSD. These PWHS scores can be helpful in cost-effectiveness studies of PTSD treatments. (Psychiatric Services 60: 1230-1238, 2009) C1 [Freed, Michael C.; Liu, Xian; Gore, Kristie L.; Engel, Charles C.] Walter Reed Army Med Ctr, Deployment Hlth Clin Ctr, Washington, DC 20307 USA. [Freed, Michael C.; Liu, Xian; Gore, Kristie L.; Engel, Charles C.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. [Yeager, Derik E.; Magruder, Kathryn M.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Yeager, Derik E.; Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Freed, MC (reprint author), Walter Reed Army Med Ctr, Deployment Hlth Clin Ctr, Bldg 2,Room 3E01,6900 Georgia Ave,NW, Washington, DC 20307 USA. EM mc_freed@onebox.com FU Veterans Affairs Health Services Research and Development [VCR-99-010-2] FX This work was partly supported by grant VCR-99-010-2 (to Dr. Magruder) funded by the Veterans Affairs Health Services Research and Development program. The authors thank Phoebe Kuesters, B. A., and Leah Russell, M. A., for their administrative support. The views expressed in this manuscript are those of the authors and do not necessarily represent the official policy or position of the Deployment Health Clinical Center, Walter Reed Army Medical Center, Uniformed Services University of the Health Sciences, Department of Defense, Department of Veterans Affairs, United States Government, or Medical University of South Carolina. NR 45 TC 7 Z9 7 U1 2 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2009 VL 60 IS 9 BP 1230 EP 1238 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 489RD UT WOS:000269438700012 PM 19723738 ER PT J AU Nestadt, G Di, CZ Riddle, MA Grados, MA Greenberg, BD Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Rasmussen, SA Cullen, B Pinto, A Knowles, JA Piacentini, J Pauls, DL Bienvenu, OJ Wang, Y Liang, KY Samuels, JF Roche, KB AF Nestadt, G. Di, C. Z. Riddle, M. A. Grados, M. A. Greenberg, B. D. Fyer, A. J. McCracken, J. T. Rauch, S. L. Murphy, D. L. Rasmussen, S. A. Cullen, B. Pinto, A. Knowles, J. A. Piacentini, J. Pauls, D. L. Bienvenu, O. J. Wang, Y. Liang, K. Y. Samuels, J. F. Roche, K. Bandeen TI Obsessive-compulsive disorder: subclassification based on co-morbidity SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Latent class; OCD; subtypes ID OCD COLLABORATIVE GENETICS; AFFECTED SIBLING PAIRS; SYMPTOM DIMENSIONS; TOURETTE-SYNDROME; LATENT STRUCTURE; ANXIETY; COMORBIDITY; FAMILY; MODELS; DEPRESSION AB Background. Obsessive-compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and co-morbid conditions to identify subtypes. Method. Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions [generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD)]. The relationship of the derived classes to specific clinical characteristics was investigated. Results. Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive disorder (MDD) is the most frequent additional disorder; (2) an OCD co-morbid tic-related class, in which tics are prominent and affective syndromes are considerably rarer; and (3) an OCD co-morbid affective-related class in which PD and affective syndromes are highly represented. The OCD co-morbid tic-related class is predominantly male and characterized by high conscientiousness. The OCD co-morbid affective-related class is predominantly female, has a young age at onset, obsessive-compulsive personality disorder (OCPD) features, high scores on the 'taboo' factor of OCD symptoms, and low conscientiousness. Conclusions. OCD can be classified into three classes based on co-morbidity. Membership within a class is differentially associated with other clinical characteristics. These classes, if replicated, should have important implications for research and clinical endeavors. C1 [Nestadt, G.; Riddle, M. A.; Grados, M. A.; Cullen, B.; Bienvenu, O. J.; Wang, Y.; Samuels, J. F.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Di, C. Z.; Liang, K. Y.; Roche, K. Bandeen] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA. [Greenberg, B. D.; Rasmussen, S. A.] Butler Hosp, Dept Psychiat & Human Behav, Brown Med Sch, Providence, RI 02906 USA. [Fyer, A. J.; Pinto, A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [McCracken, J. T.; Piacentini, J.; Pauls, D. L.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Rauch, S. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rauch, S. L.] Massachusetts Gen Hosp, Neurodev Genet Unit, Boston, MA 02114 USA. [Rauch, S. L.] Harvard Univ, Sch Med, Boston, MA USA. [Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Knowles, J. A.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. RP Nestadt, G (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 109, Baltimore, MD 21287 USA. EM gnestadt@jhmi.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU National Institute of Health [R01-MH-50214, K23-MH-64543]; NIH/NCRR/OPD-GCRC [RR00052] FX We thank the many families participating in the study, Drs D. Housman, K. Merikangas, A. Pulver and A. Wilson for consultation, and clinicians and coordinators at each site. This work was funded by National Institute of Health grants R01-MH-50214, K23-MH-64543 and NIH/NCRR/OPD-GCRC RR00052. NR 44 TC 41 Z9 43 U1 4 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD SEP PY 2009 VL 39 IS 9 BP 1491 EP 1501 DI 10.1017/S0033291708004753 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 486CP UT WOS:000269173400009 PM 19046474 ER PT J AU King, DW Orazem, RJ Lauterbach, D King, LA Hebenstreit, CL Shalev, AY AF King, Daniel W. Orazem, Robert J. Lauterbach, Dean King, Lynda A. Hebenstreit, Claire L. Shalev, Arieh Y. TI Factor Structure of Posttraumatic Stress Disorder as Measured by the Impact of Event Scale-Revised: Stability Across Cultures and Time SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress disorder; Impact of Event Scale-Revised; confirmatory factor analysis; invariance AB This study examined the structure of posttraumatic stress disorder (PTSD):as measured by the Impact of Event Scale Revised (IES-R; Weiss & Marmar, 1997); tested factorial invariance for samples of 235 Israeli emergency room patients and 306 U.S. undergraduate students, and then. evaluated factorial invariance over multiple occasions within the emergency room sample. A four-factor structure representing intrusion, avoidance-numbing, hyperarousal, and sleep emerged as the preferred model. Configural invariance over groups was supported for this model. Likewise configural invariance over occasions was demonstrated, but metric invariance was not fully supported, with variation in the loadings on the intrusion factor over time seemingly the source Of misfit. Interpretations and conclusions center on sleep as a separate factor underlying the structure of the IES-R, the distinction between avoidance and numbing as a function of how the IES-R (vs. the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) operationalizes the numbing feature of PTSD and possible shifts in the meaning of intrusion over time. C1 [King, Daniel W.; Orazem, Robert J.; King, Lynda A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [King, Daniel W.; King, Lynda A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [King, Daniel W.; Orazem, Robert J.; King, Lynda A.; Hebenstreit, Claire L.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. [King, Daniel W.; King, Lynda A.; Hebenstreit, Claire L.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. [Shalev, Arieh Y.] Hadassah Univ Hosp, Arieh Shalev Ctr Traumat Stress, IL-91120 Jerusalem, Israel. [Shalev, Arieh Y.] Hadassah Univ Hosp, Dept Psychiat, IL-91120 Jerusalem, Israel. [Lauterbach, Dean] Eastern Michigan Univ, Ypsilanti, MI 48197 USA. RP King, DW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B5, 150 S Huntington Ave, Boston, MA 02130 USA. EM danking@bu.edu NR 66 TC 26 Z9 26 U1 4 U2 13 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD SEP PY 2009 VL 1 IS 3 BP 173 EP 187 DI 10.1037/a0016990 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA V16NJ UT WOS:000207876000001 ER PT J AU Zhang, XY Chen, DC Qi, LY Wang, F Xiu, MH Chen, S Wu, GY Kosten, TA Kosten, TR AF Zhang, Xiang Yang Chen, Da Chun Qi, Ling Yan Wang, Fang Xiu, Mei Hong Chen, Song Wu, Gui Ying Kosten, Therese A. Kosten, Thomas R. TI Gender differences in the prevalence, risk and clinical correlates of tardive dyskinesia in Chinese schizophrenia SO PSYCHOPHARMACOLOGY LA English DT Article DE Schizophrenia; Gender difference; Tardive dyskinesia; Prevalence; Risk factor; Antipsychotic; Chinese ID ATYPICAL ANTIPSYCHOTICS; PSYCHIATRIC-PATIENTS; NEGATIVE SYMPTOMS; EXTRAPYRAMIDAL SYNDROMES; TYPICAL ANTIPSYCHOTICS; OLDER PATIENTS; HONG-KONG; OUTPATIENTS; POPULATION; DRUGS AB Despite extensive use of antipsychotic drug treatment, few studies address the prevalence of tardive dyskinesia (TD) in homogeneous ethnic groups such as the Chinese. This study examined gender-specific relationships between TD and symptom levels in schizophrenia among Han Chinese, which have previously received little systematic study. Five hundred and twenty-two inpatients with schizophrenia receiving long-term treatment with antipsychotics were evaluated with the AIMS. The patient's psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). Demographic and clinical data were collected from a detailed questionnaire and medical records. The overall TD prevalence was 33.7% with rates of 39.2% (138/352) in males and 22.4% (38/170) in females (chi (2) = 14.6, df = 1, p < 0.0001; adjust odds ratio 2.06; CI, 1.32-3.16). The AIMS score in patients with TD was lower in females than males (5.3 +/- 3.9 vs 6.7 +/- 3.7, t = 2.52, p < 0.01) after adjustment for the significant covariates. TD was associated with the negative symptoms on the PANSS in both genders, and with age, PANSS total and positive symptoms in men, not women. Our present findings suggest that there are gender differences in the prevalence, risk, and clinical correlates of TD in schizophrenia. Although this study is limited by cross-sectional designs, the magnitude of these gender-specific differences is substantial and deservers further prospective study. C1 [Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] VA Med Ctr, Houston, TX 77030 USA. [Zhang, Xiang Yang; Chen, Da Chun; Qi, Ling Yan; Wang, Fang; Xiu, Mei Hong; Chen, Song] Beijing HuiLongGuan Hosp, Ctr Biol Psychiat, Beijing 100096, Peoples R China. [Zhang, Xiang Yang; Wu, Gui Ying] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu FU Beijing Municipal Natural Science Foundation [ID: 7072035]; Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs; United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX Supported by grants from the Beijing Municipal Natural Science Foundation (ID: 7072035), the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center ( MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827, and U01-MH79639. NR 51 TC 14 Z9 15 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2009 VL 205 IS 4 BP 647 EP 654 DI 10.1007/s00213-009-1590-8 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 477JD UT WOS:000268514400009 PM 19529921 ER PT J AU Pineles, SL Orr, MR Orr, SP AF Pineles, Suzanne L. Orr, Matthew R. Orr, Scott P. TI An alternative scoring method for skin conductance responding in a differential fear conditioning paradigm with a long-duration conditioned stimulus SO PSYCHOPHYSIOLOGY LA English DT Article DE Conditioning; Electrodermal response (skin electric response); Scoring methods ID POTENTIALLY PHOBIC STIMULI; HUMAN AUTONOMIC RESPONSES; ELECTRODERMAL RESPONSES; UNCONDITIONAL STIMULUS; ORIENTING RESPONSES; FACIAL EXPRESSIONS; RELEVANT STIMULI; INTERSTIMULUS-INTERVAL; STARTLE MODULATION; COGNITIVE-FACTORS AB Researchers examining skin conductance (SC) as a measure of aversive conditioning commonly separate the SC response into two components when the CS-UCS interval is sufficiently long. This convention drew from early theorists who described these components, the first- and second-interval responses, as measuring orienting and conditional responses, respectively. The present report critically examines this scoring method through a literature review and a secondary data analysis of a large-scale study of police and firefighter trainees that used a differential aversive conditioning procedure (n=287). The task included habituation, acquisition, and extinction phases, with colored circles as the CSs and shocks as the UCS. Results do not support the convention of separating the SC response into first- and second-interval responses. It is recommended that SC response scores be derived from data obtained across the entire CS-UCS interval. C1 [Pineles, Suzanne L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Pineles, Suzanne L.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Orr, Matthew R.] Univ Alabama, Dept Phys, Huntsville, MA USA. [Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Orr, Scott P.] Harvard Univ, Sch Med, Charlestown, MA USA. [Orr, Scott P.] Dept Vet Affairs Med Ctr, Manchester, NH USA. RP Orr, SP (reprint author), VA Med Ctr, Res Serv 151, 718 Smyth Rd, Manchester, NH 03104 USA. EM scott.orr@va.gov FU U.S. Public Health Service [R01-MH60315]; Department of Veterans Affairs; Department of Veterans Affairs, Clinical Sciences RD Service FX This research was supported by U.S. Public Health Service grant R01-MH60315 and Department of Veterans Affairs Merit Review grant to Scott P. Orr. Additional support was provided to Suzanne Pineles by the Department of Veterans Affairs, Clinical Sciences R&D Service, Career Development Award Program. We thank Heike Croteau, Michael Macklin, Sgt. Thomas Flemming, Sheeva Mostou., and Erin Rowe for their assistance with this project. We would also like to express our appreciation to the police and. re. ghters for their willingness to participate. NR 83 TC 43 Z9 43 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2009 VL 46 IS 5 BP 984 EP 995 DI 10.1111/j.1469-8986.2009.00852.x PG 12 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 493NK UT WOS:000269743700009 PM 19558401 ER PT J AU Bogdan, R Santesso, DL Fagerness, J Perlis, RH Pizzagalli, DA AF Bogdan, Ryan Santesso, Diane L. Fagerness, Jesen Perlis, Roy H. Pizzagalli, Diego A. TI CORTICOTROPIN-RELEASING HORMONE TYPE 1 RECEPTOR (CRHR1) POLYMORPHISMS AND STRESS INTERACT TO INFLUENCE REWARD PROCESSING: IMPLICATIONS FOR DEPRESSION SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 49th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 21-24, 2009 CL Berlin, GERMANY SP Soc Psychophysiol Res C1 [Bogdan, Ryan; Santesso, Diane L.; Perlis, Roy H.; Pizzagalli, Diego A.] Harvard Univ, Cambridge, MA 02138 USA. [Fagerness, Jesen] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2009 VL 46 BP S13 EP S13 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 493NR UT WOS:000269744700062 ER PT J AU Eggert, LD Holzel, BK Quirin, MR Pruessner, JC Lazar, SW AF Eggert, Lucas D. Holzel, Britta K. Quirin, Markus R. Pruessner, Jens C. Lazar, Sara W. TI DIFFERENCES IN GRAY MATTER VOLUME ASSOCIATED WITH INSIGHT MEDITATION: A VOXEL-BASED MORPHOMETRY STUDY SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 49th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 21-24, 2009 CL Berlin, GERMANY SP Soc Psychophysiol Res DE meditation; voxel-based morphometry; attention C1 [Eggert, Lucas D.; Quirin, Markus R.] Univ Osnabruck, D-4500 Osnabruck, Germany. [Holzel, Britta K.; Lazar, Sara W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pruessner, Jens C.] McGill Ctr Studies Aging, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 1 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2009 VL 46 BP S118 EP S118 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 493NR UT WOS:000269744700665 ER PT J AU Kaufmann, C Beucke, JC Simon, D Kathmann, N AF Kaufmann, Christian Beucke, Jan-Carl Simon, Daniela Kathmann, Norbert TI IMPAIRED CORTICO-STRIATAL CONNECTIVITY FOR LOSS IN THE REWARD CIRCUITRY OF OBSESSIVE-COMPULSIVE DISORDER (OCD) SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 49th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 21-24, 2009 CL Berlin, GERMANY SP Soc Psychophysiol Res DE psychophysiological interaction; obessive-compulsive disorder; reward circuitry C1 [Kaufmann, Christian; Simon, Daniela; Kathmann, Norbert] Humboldt Univ, Berlin, Germany. [Beucke, Jan-Carl] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2009 VL 46 BP S74 EP S74 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 493NR UT WOS:000269744700411 ER PT J AU Kelley, JM Lembo, AJ Ablon, JS Villanueva, JJ Conboy, LA Levy, R Marci, CD Kerr, CE Kirsch, I Jacobson, EE Riess, H Kaptchuk, TJ AF Kelley, John M. Lembo, Anthony J. Ablon, J. Stuart Villanueva, Joel J. Conboy, Lisa A. Levy, Ray Marci, Carl D. Kerr, Catherine E. Kirsch, Irving Jacobson, Eric E. Riess, Helen Kaptchuk, Ted J. TI Patient and Practitioner Influences on the Placebo Effect in Irritable Bowel Syndrome SO PSYCHOSOMATIC MEDICINE LA English DT Article DE placebo effect; irritable bowel syndrome; acupuncture; personality; patient-practitioner relationship ID COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT; COGNITIVE-BEHAVIORAL THERAPY; NATIONAL-INSTITUTE; CLINICAL-TRIALS; END-POINT; ADEQUATE RELIEF; PSYCHOTHERAPY; OUTCOMES; IMPROVEMENT AB Objective: To determine whether placebo responses can be explained by characteristics of the patient, the practitioner, or their interpersonal interaction. Methods: We performed an analysis of videotape and psychometric data from a clinical trial of patients with irritable bowel syndrome who were treated with placebo acupuncture in either a warm empathic interaction (Augmented, n = 96), a neutral interaction (Limited, n = 97), or a waitlist control (Waitlist, n = 96). We examined the relationships between the placebo response and a) patient personality and demographics; b) treating practitioner; and c) the patient-practitioner interaction as captured on videotape and rated by the Psychotherapy Process Q-Set. Results: Patient extraversion, agreeableness, openness to experience, and female gender were associated with placebo response, but these effects held only in the augmented group. Regression analyses controlling for all other independent variables suggest that only extraversion is an independent predictor of placebo response. There were significant differences between practitioners in outcomes; this effect was twice as large as the effect attributable to treatment group assignment. Videotape analysis indicated that the augmented group fostered a treatment relationship similar to a prototype of an ideal healthcare interaction. Conclusions: Personality and gender influenced the placebo response, but only in the warm, empathic, augmented group. This suggests that, to the degree a placebo effect is evoked by the patient-practitioner relationship, personality characteristics of the patient will be associated with the placebo response. In addition, practitioners differed markedly in effectiveness, despite standardized interactions. We propose that the quality of the patient-practitioner interaction accounts for the significant difference between the groups in placebo response. C1 [Kelley, John M.] Endicott Coll, Dept Psychol, Beverly, MA 01915 USA. [Kelley, John M.; Ablon, J. Stuart; Villanueva, Joel J.; Levy, Ray; Marci, Carl D.; Riess, Helen] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Conboy, Lisa A.; Kerr, Catherine E.; Kaptchuk, Ted J.] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kirsch, Irving] Univ Hull, Dept Psychol, Kingston Upon Hull HU6 7RX, N Humberside, England. [Jacobson, Eric E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. RP Kelley, JM (reprint author), Endicott Coll, Dept Psychol, 376 Hale St, Beverly, MA 01915 USA. EM JohnKelley@Post.Harvard.Edu RI Kerr, Catherine/D-3299-2009 FU National Center for Complementary and Alternative Medicine (NCCAM) [1 R21 AT002564, 1 K24 AT004095, 1R01 AT001414-01] FX This publication was made possible by Grant 1 R21 AT002564 (J.M.K., J.S.A., JJ V., R.L., CD.M.; I.K., H.R., TJX), Grant 1 K24 AT004095 (T.J.K.), and Grant 1R01 AT001414-01 (J.M.K., A.JL., LAC, CE.K., E.E.J, H.R., TJK) from the National Center for Complementary and Alternative Medicine (NCCAM). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, or the National Institutes Of Health. NR 55 TC 88 Z9 88 U1 2 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP PY 2009 VL 71 IS 7 BP 789 EP 797 DI 10.1097/PSY.0b013e3181acee12 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 497JT UT WOS:000270056100014 PM 19661195 ER PT J AU Farabaugh, AH Locascio, JJ Yap, L Weintraub, D McDonald, WM Agoston, M Alpert, JE Growdon, J Fava, M AF Farabaugh, Amy H. Locascio, Joseph J. Yap, Liang Weintraub, Daniel McDonald, William M. Agoston, Monica Alpert, Jonathan E. Growdon, John Fava, Maurizio TI Pattern of Depressive Symptoms in Parkinson's Disease SO PSYCHOSOMATICS LA English DT Article ID COMORBIDITY; PROGRESSION; PREVALENCE AB Background: Depressive symptoms are common in Parkinson's disease (PD); however, it is unclear whether there are specific depressive symptom patterns in patients with PD and comorbid depression (dPD). Objective: The goal of this study is to examine the frequency and correlates of specific depressive symptoms in PD. Method: A sample of 158 individuals with PD completed the self-rated Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS). By multiple-regression analysis, the authors examined the association between HANDS total and subscale scores and various demographic variables. Results: The frequency of depression was 37% (N = 58). Patients with a history of depression before PD had significantly more serious depression than those who had no such history. Of those who were more depressed, the most common symptoms of depression endorsed were low energy, difficulty with concentration/making decisions, feeling blue, feeling hopeless, and having poor sleep. Conclusion: There is a relatively high prevalence of dPD. Items on the HANDS that discriminated best between depressed and nondepressed subjects with PD included feeling blue, feeling hopeless, feeling worthless, lack of interest, and self-blame. It remains to be defined whether dPD should be understood primarily as a psychological reaction to a physical disability or perceived impending one, or as a direct expression of the neuropathology of PD. (Psychosomatics 2009; 50: 448-454) C1 [Farabaugh, Amy H.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Movement Disorders Unit, Boston, MA 02114 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. RP Farabaugh, AH (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM afarabaugh@partners.org OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [K23 MH067894] NR 25 TC 9 Z9 11 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2009 VL 50 IS 5 BP 448 EP 454 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 510OY UT WOS:000271100700003 PM 19855029 ER PT J AU Paddison, J Fricchione, G Gandhi, RT Freudenreich, O AF Paddison, Johanna Fricchione, Gregory Gandhi, Rajesh T. Freudenreich, Oliver TI Fatigue in Psychiatric HIV Patients: A Pilot Study of Psychological Correlates SO PSYCHOSOMATICS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SLEEP QUALITY INDEX; DEPRESSIVE SYMPTOMS; ANTIRETROVIRAL THERAPY; AMBULATORY PATIENTS; INFECTED PATIENTS; OF-LIFE; WOMEN; AIDS; PROGRESSION AB Background: Even though viral management of HIV infection is now more effective, clinical observations suggest that fatigue remains a problem for a substantial proportion of patients. Objective: The authors delineated prevalence and severity of fatigue in HIV patients with psychiatric comorbidities and examined psychological correlates of fatigue. Method: The authors comprehensively assessed fatigue in 38 consecutive HIV patients referred for psychiatric treatment with the Identity-Consequence Fatigue Scale. Results: About 80% of patients reported at least moderate feelings of fatigue, and about 25% judged that fatigue was severely affecting their daily functioning. Depression, anxiety, and perceived stress explained between 20% and 75% of the variance in fatigue ratings. Discussion: The results suggest that fatigue in the era of effective antiretroviral treatment is prevalent, relevant, and related to psychological morbidities. Recognition and treatment of these comorbidities may be important in reducing this fatigue. (Psychosomatics 2009; 50: 455-460) C1 Div Psychiat & Med, Boston, MA USA. AIDS Res Ctr, Div Infect Dis & Partners, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Freudenreich, O (reprint author), Freedom Trail Clin, MGH Schizophrenia Program, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. EM ofreudenreich@partners.org FU Fulbright Fellowship; Benson Henry Institute, both at Massachusetts General Hospital FX Johanna Paddison was supported by a Fulbright Fellowship, which allowed her to spend time with the Division of Psychiatry and Medicine, and the Benson Henry Institute, both at Massachusetts General Hospital. NR 29 TC 7 Z9 8 U1 5 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2009 VL 50 IS 5 BP 455 EP 460 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 510OY UT WOS:000271100700004 PM 19855030 ER PT J AU Hauser, P Morasco, BJ Linke, A Bjornson, D Ruimy, S Matthews, A Rifai, A Indest, DW Loftis, JM AF Hauser, Peter Morasco, Benjamin J. Linke, Alex Bjornson, Dannell Ruimy, Samantha Matthews, Annette Rifai, Aly Indest, David W. Loftis, Jennifer M. TI Antiviral Completion Rates and Sustained Viral Response in Hepatitis C Patients With and Without Preexisting Major Depressive Disorder SO PSYCHOSOMATICS LA English DT Article ID ALPHA-INDUCED DEPRESSION; SUBSTANCE USE DISORDERS; INTERFERON-ALPHA; PSYCHIATRIC-DISORDERS; VIRUS-INFECTION; PLUS RIBAVIRIN; THERAPY; VETERANS; ILLNESS AB Background: Despite evidence suggesting that the majority of patients with hepatitis C virus (HCV) have psychiatric and substance use disorders, patients with these comorbidities have historically been excluded from antiviral therapy for HCV. Objective: The authors compared antiviral completion and sustained virologic response (SVR) rates between hepatitis C ( HCV) patients with versus those without preexisting major depressive disorder (MDD). Method: The authors performed a chart review of HCV patients ( 30 with MDD and 25 control subjects) who attended an optional HCV education class and signed informed consent allowing collection of clinical data. Results: The MDD group had completion and SVR rates similar to those of control subjects. Neuropsychiatric side effects and reasons for discontinuation of treatment were not different between groups. Conclusion: Patients with MDD can be safely and effectively treated with antiviral therapy. (Psychosomatics 2009; 50: 500-505) C1 [Hauser, Peter] Portland VA Med Ctr, NW Hepatitis Resource Ctr C, Portland, OR 97202 USA. Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97202 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Portland VA Med Ctr, JENS Lab, Portland, OR 97202 USA. Oregon Hlth & Sci Univ, Dept Internal Med, Div Gastroenterol, Portland, OR 97201 USA. RP Hauser, P (reprint author), Portland VA Med Ctr, NW Hepatitis Resource Ctr C, 3710 SW US Vet Hosp Rd,POB 1035 V3MHC, Portland, OR 97202 USA. EM peter.hauser2@med.va.gov FU VA Merit Review Program, Northwest Hepatitis C Resource Center, Janssen Pharmaceuticals; NIH [K23DA023467-01A1]; VA Clinical Sciences Research Development FX Dr. Hauser receives research/grant support from the VA Merit Review Program, Northwest Hepatitis C Resource Center, Janssen Pharmaceuticals, and is currently on the speaker's bureau for Astra Zeneca and Jazz Pharmaceutical. Dr. Morasco receives support from the NIH (K23DA023467-01A1). Drs. Matthews and Loftis are supported by VA Clinical Sciences Research & Development career development awards. NR 26 TC 14 Z9 14 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2009 VL 50 IS 5 BP 500 EP 505 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 510OY UT WOS:000271100700010 PM 19855036 ER PT J AU Dang, PA Kalra, MK Schultz, TJ Graham, SA Dreyer, KJ AF Dang, Pragya A. Kalra, Mannudeep K. Schultz, Thomas J. Graham, Steven A. Dreyer, Keith J. TI Render: An Online Searchable Radiology Study Repository SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 93rd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 25-30, 2007 CL Chicago, IL SP Radiol Soc N Amer ID IMAGE RESOURCE CENTER; TEACHING FILE; UPDATE; PACS; TOOL AB Radiology departments are a rich source of information in the form of digital radiology reports and images obtained in patients with a wide spectrum of clinical conditions. A free text radiology report and image search application known as Render was created to allow users to find pertinent cases for a variety of purposes. Render is a radiology report and image repository that pools researchable information derived from multiple systems in near real time with use of (a) Health Level 7 links for radiology information system data, (b) periodic file transfers from the picture archiving and communication system, and (c) the results of natural language processing (NLP) analysis. Users can perform more structured and detailed searches with this application by combining different imaging and patient characteristics such as examination number; patient age, gender, and medical record number; and imaging modality. Use of NLP analysis allows a more effective search for reports with positive findings, resulting in the retrieval of more cases and terms having greater relevance. From the retrieved results, users can save images, bookmark examinations, and navigate to an external search engine such as Google. Render has applications in the fields of radiology education, research, and clinical decision support. (C) RSNA, 2009. radiographics.rsna.org C1 [Dang, Pragya A.; Kalra, Mannudeep K.; Schultz, Thomas J.; Graham, Steven A.; Dreyer, Keith J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Dreyer, KJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400E, Boston, MA 02114 USA. EM kdreyer@partners.org NR 12 TC 15 Z9 15 U1 2 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2009 VL 29 IS 5 BP 1233 EP U38 DI 10.1148/rg.295085036 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 496PK UT WOS:000269987100002 PM 19564253 ER PT J AU Ma, XZ Holalkere, NS Kambadakone, A Mino-Kenudson, M Hahn, PF Sahani, DV AF Ma, Xiaozhou Holalkere, Nagaraj-Setty Kambadakone, Avinash Mino-Kenudson, Mari Hahn, Peter F. Sahani, Dushyant V. TI Imaging-based Quantification of Hepatic Fat: Methods and Clinical Applications SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 91st Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 27-DEC 02, 2005 CL Chicago, IL SP Radiol Soc N Amer ID MAGNETIC-RESONANCE-SPECTROSCOPY; DIFFUSE LIVER-DISEASE; DUAL-ENERGY CT; PROTON MR SPECTROSCOPY; CONTRAST-ENHANCED CT; NONALCOHOLIC STEATOHEPATITIS; COMPUTED-TOMOGRAPHY; DIXON TECHNIQUE; GRADIENT-ECHO; IN-VIVO AB Fatty liver disease comprises a spectrum of conditions (simple hepatic steatosis, steatohepatitis with inflammatory changes, and end-stage liver disease with fibrosis and cirrhosis). Hepatic steatosis is often associated with diabetes and obesity and may be secondary to alcohol and drug use, toxins, viral infections, and metabolic diseases. Detection and quantification of liver fat have many clinical applications, and early recognition is crucial to institute appropriate management and prevent progression. Histopathologic analysis is the reference standard to detect and quantify fat in the liver, but results are vulnerable to sampling error. Moreover, it can cause morbidity and complications and cannot be repeated often enough to monitor treatment response. Imaging can be repeated regularly and allows assessment of the entire liver, thus avoiding sampling error. Selection of appropriate imaging methods demands understanding of their advantages and limitations and the suitable clinical setting. Ultrasonography is effective for detecting moderate or severe fatty infiltration but is limited by lack of interobserver reliability and intraobserver reproducibility. Computed tomography allows quantitative and qualitative evaluation and is generally highly accurate and reliable; however, the results may be confounded by hepatic parenchymal changes due to cirrhosis or depositional diseases. Magnetic resonance (MR) imaging with appropriate sequences (eg, chemical shift techniques) has similarly high sensitivity, and MR spectroscopy provides unique advantages for some applications. However, both are expensive and too complex to be used to monitor steatosis. (C) RSNA, 2009. radiographics.rsna.org C1 [Ma, Xiaozhou; Holalkere, Nagaraj-Setty; Kambadakone, Avinash; Hahn, Peter F.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org OI Holalkere, Nagaraj/0000-0001-6324-7682 NR 130 TC 90 Z9 100 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2009 VL 29 IS 5 BP 1253 EP U73 DI 10.1148/rg.295085186 PG 26 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 496PK UT WOS:000269987100004 PM 19755595 ER PT J AU Farsad, K Kattapuram, SV Sacknoff, R Ono, J Nielsen, GP AF Farsad, Khashayar Kattapuram, Susan V. Sacknoff, Richard Ono, Jill Nielsen, Gunnlaugur P. TI Best Cases from the AFIP Sacral Chordoma SO RADIOGRAPHICS LA English DT Article ID RADIOFREQUENCY ABLATION; MYXOPAPILLARY EPENDYMOMA; PRIMARY TUMORS; EXPERIENCE; SPINE C1 [Farsad, Khashayar; Kattapuram, Susan V.; Sacknoff, Richard] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ono, Jill; Nielsen, Gunnlaugur P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Farsad, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM kfarsad@partners.org NR 22 TC 11 Z9 11 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2009 VL 29 IS 5 BP 1525 EP 1530 DI 10.1148/rg.295085215 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 496PK UT WOS:000269987100021 PM 19755609 ER PT J AU Choy, G Pomerantz, SR AF Choy, Garry Pomerantz, Stuart R. TI Net Assets: The Social Web for Radiology. Part II. Social Networking for Radiologists SO RADIOLOGY LA English DT Editorial Material C1 [Choy, Garry] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Pomerantz, Stuart R.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Choy, G (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Gray 2-B285, Boston, MA 02114 USA. EM netassets@rsna.org NR 3 TC 2 Z9 2 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2009 VL 252 IS 3 BP 642 EP 646 DI 10.1148/radiol.2523090869 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 506WZ UT WOS:000270809500004 PM 19717749 ER PT J AU Abujudeh, HH Kaewlai, R Choy, G Whelton, DG Rosenthal, DI AF Abujudeh, Hani H. Kaewlai, Rathachai Choy, Garry Whelton, Dianne G. Rosenthal, Daniel I. TI Important Imaging Finding E-mail Alert System: Experience after 3 Years of Implementation SO RADIOLOGY LA English DT Article ID RADIOLOGISTS DUTY AB Purpose: To evaluate the effectiveness of an important finding alert (IFA) system that uses e-mail technology to alert referring physicians to an important but nonurgent imaging finding. Materials and Methods: The institutional review board approved the study; the requirement for informed consent was waived. The authors retrospectively reviewed the radiology reports generated from January 2005 to December 2007 to determine how many reports contained an IFA statement, how many IFA messages were sent, and how many such messages were viewed by referring physicians. They reviewed 1000 randomly selected radiology reports that contained the IFA statement to identify the imaging modalities and findings that triggered the radiologists' use of the IFA system. Results: A total of 1540254 radiology reports were generated during the 3-year period. A total of 56 691 (3.7%) reports contained the IFA statement. IFA e-mail messages were sent for 52 883 (93.3%) of the 56 691 reports, and 42 285 (74.6%) of the 56 691 reports were viewed by the referring physicians. The most common important but nonurgent findings were definitive (449 [44.9%] of 1000 reports) and indeterminate (260 [26.0%] of 1000 reports) abnormalities. More than half (n = 503) of the alerts were related to computed tomographic examinations, and the majority (n = 677, 67.7%) of them were initiated by thoracic and abdominal radiologists. Conclusion: The IFA system is a potentially useful method of communicating nonurgent but important imaging findings with use of e-mail technology. (C) RSNA, 2009 C1 [Abujudeh, Hani H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND-210, Boston, MA 02114 USA. EM habujudeh@partners.org NR 11 TC 19 Z9 19 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2009 VL 252 IS 3 BP 747 EP 753 DI 10.1148/radiol.2531082217 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 506WZ UT WOS:000270809500016 PM 19703870 ER PT J AU Terroni, LDN Fraguas, R de Lucia, M Tinone, G Mattos, P Iosifescu, DV Scaf, M AF Niro Terroni, Luisa de Marillac Fraguas, Renerio de Lucia, Mara Tinone, Gisela Mattos, Patricia Iosifescu, Dan V. Scaf, Milberto TI Importance of retardation and fatigue/interest domains for the diagnosis of major depressive episode after stroke: a four months prospective study SO REVISTA BRASILEIRA DE PSIQUIATRIA LA English DT Article DE Stroke; Depression; Depressive disorder, major; Signs and symptoms; Clustering ID POSTSTROKE DEPRESSION; MYOCARDIAL-INFARCTION; COGNITIVE IMPAIRMENT; COMMUNITY STROKE; SOMATIC SYMPTOMS; FOLLOW-UP; MOOD; PREVALENCE; DISORDERS; PREDICTORS AB Objective: Post-stroke major depressive episode is very frequent, but underdiagnosed. Researchers have investigated major depressive episode symptomatology, which may increase its detection. This study was developed to identify the depressive symptoms that better differentiate post-stroke patients with major depressive episode from those without major depressive episode. Method: We screened 260 consecutive ischemic stroke patients admitted to the neurology clinic of a university hospital. Seventy-three patients were eligible and prospectively evaluated. We assessed the diagnosis of major depressive episode using the Structured Clinical Interview for DSM-IV and the profile of depressive symptoms using the 31-item version of the Hamilton Depression Rating Scale. For data analysis we used cluster analyses and logistic regression equations. Results: Twenty-one (28.8%) patients had a major depressive episode. The odds ratio of being diagnosed with major depressive episode was 3.86; (95% CI, 1.23-12.04) for an increase of one unit in the cluster composed by the domains of fatigue/interest and retardation, and 2.39 (95% CI, 1.21-4.71) for an increase of one unit in the cluster composed by the domains of cognitive, accessory and anxiety symptoms. The domains of eating/weight and insomnia did not contribute for the major depressive episode diagnosis. Conclusion: The domains of retardation and interest/fatigue are the most relevant for the diagnosis of major depressive episode after stroke. C1 [Niro Terroni, Luisa de Marillac; Fraguas, Renerio; Mattos, Patricia] Univ Sao Paulo, Sch Med, Clin Hosp, Inst Psychiat,Liaison Psychiat Grp, Sao Paulo, Brazil. [Niro Terroni, Luisa de Marillac; Fraguas, Renerio; Mattos, Patricia] Univ Sao Paulo, Sch Med, Clin Hosp, Dept Psychiat,Liaison Psychiat, Sao Paulo, Brazil. [de Lucia, Mara] Univ Sao Paulo, Sch Med, Clin Hosp, Inst Psychiat,Phychol Div, Sao Paulo, Brazil. [Tinone, Gisela; Scaf, Milberto] Univ Sao Paulo, Sch Med, Clin Hosp, Inst Psychiat,Dept Neurol, Sao Paulo, Brazil. [Fraguas, Renerio; Iosifescu, Dan V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, Cambridge, MA 02138 USA. RP Terroni, LDN (reprint author), Univ Sao Paulo, Sch Med, Clin Hosp, Inst Psychiat,Liaison Psychiat Grp, R Ovidio Pires Campos 785, Sao Paulo, Brazil. EM luisaterroni@usp.br NR 39 TC 5 Z9 7 U1 2 U2 3 PU ASSOC BRASILEIRA PSIQUIATRIA PI SAO PAULO PA SUBSCRIPTION DEPARTMENT, RUA PEDRO DE TOLEDO, 967 - CASA 01, SAO PAULO, SP 04039-032 A, BRAZIL SN 1516-4446 J9 REV BRAS PSIQUIATR JI Rev. Bras. Psiquiatr. PD SEP PY 2009 VL 31 IS 3 BP 202 EP 207 PG 6 WC Psychiatry SC Psychiatry GA 499NW UT WOS:000270229900003 ER PT J AU Zhang, XY Chen, DC Xiu, MH Wang, F Qi, LY Sun, HQ Chen, S He, SC Wu, GY Haile, CN Kosten, TA Lu, L Kosten, TR AF Zhang, Xiang Yang Chen, Da Chun Xiu, Mei Hong Wang, Fan Qi, Ling Yan Sun, Hong Qang Chen, Song He, Shu Chang Wu, Gui Ying Haile, Colin N. Kosten, Therese A. Lu, Lin Kosten, Thomas R. TI The novel oxidative stress marker thioredoxin is increased in first-episode schizophrenic patients SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Oxidative stress; Free radical; Thioredoxin; Psychopathology ID ATYPICAL ANTIPSYCHOTIC-DRUGS; ANTIOXIDANT DEFENSE SYSTEM; BLOOD SUPEROXIDE-DISMUTASE; FREE-RADICAL PATHOLOGY; TARDIVE-DYSKINESIA; LIPID-PEROXIDATION; THERAPEUTIC IMPLICATIONS; PLASMA THIOREDOXIN; REDOX REGULATION; DIFFERENT FORMS AB Excessive free radical production leading to oxidative stress may be involved in the pathophysiology of schizophrenia. oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in various stages of schizophrenia. Serum TRX levels were determined using ELISA from 60 never-medicated first-episode and 66 medicated chronic schizophrenia patients and 66 healthy control subjects matched for age and gender. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed that group comparison between first-episode and chronic patients and control groups revealed significantly increased serum TRX only in first-episode patients. Increased levels of TRX in patients experiencing an acute stage schizophrenic episode was also significantly higher compared to chronic schizophrenic patients on antipsychotic medication. Serum TRX was also positively correlated with positive symptoms of schizophrenia. Our results suggest oxidative stress occurs in an acute stage of schizophrenic episode and may have an important role in pathogenesis and symptomology of schizophrenia. Lower TRX levels in chronic patients treated with antipsychotics may have implications for treatment outcome. (C) 2009 Elsevier B.V. All rights reserved. C1 [Zhang, Xiang Yang] Baylor Coll Med, VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang; Chen, Da Chun; Xiu, Mei Hong; Wang, Fan; Qi, Ling Yan; Sun, Hong Qang; Chen, Song] Beijing HuiLongGuan Hosp, Ctr Biol Psychiat, Beijing, Peoples R China. [He, Shu Chang] Peking Univ, Dept Psychol, Beijing 100871, Peoples R China. [Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100871, Peoples R China. RP Zhang, XY (reprint author), Baylor Coll Med, VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu OI Haile, Colin/0000-0001-8293-7291 FU Stanley Medical Research Institute [03T-459, 05T-726]; Beijing Municipal Natural Science Foundation [7072035]; Department of Veterans Affairs, VISN 16; Mental Illness Research, Education and Clinical Center (MIRECC); United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX Funding for this study was provided by grants from the Stanley Medical Research Institute (03T-459 and 05T-726), the Beijing Municipal Natural Science Foundation (7072035) and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. These sources had no further role in the 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 57 TC 42 Z9 42 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2009 VL 113 IS 2-3 BP 151 EP 157 DI 10.1016/j.schres.2009.05.016 PG 7 WC Psychiatry SC Psychiatry GA 492CD UT WOS:000269630800005 PM 19540723 ER PT J AU Bartzokis, G Lu, PH Stewart, SB Oluwadara, B Lucas, AJ Pantages, J Pratt, E Sherin, JE Altshuler, LL Mintz, J Gitlin, MJ Subotnik, KL Nuechterlein, KH AF Bartzokis, George Lu, Po H. Stewart, Stephanie B. Oluwadara, Bolanle Lucas, Andrew J. Pantages, Joanna Pratt, Erika Sherin, Jonathan E. Altshuler, Lori L. Mintz, Jim Gitlin, Michael J. Subotnik, Kenneth L. Nuechterlein, Keith H. TI In vivo evidence of differential impact of typical and atypical antipsychotics on intracortical myelin in adults with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 07-11, 2008 CL Scottsdale, AZ SP Amer Coll Neuropsychopharmacol DE Schizophrenia; Second generation antipsychotic medication; Atypical; Intracortical myelin; White matter; Gray matter; Oligodendrocyte; Trajectory; Development; Lipid; Age; Prevention ID MAJOR DEPRESSIVE DISORDER; DORSOLATERAL PREFRONTAL CORTEX; INCREASES CELL-PROLIFERATION; MATTER STRUCTURAL INTEGRITY; WHITE-MATTER; BIPOLAR DISORDER; GRAY-MATTER; NEUROPSYCHIATRIC DISORDERS; DEVELOPMENTAL DISORDERS; MORPHOMETRIC ANALYSIS AB Context: Imaging and post-mortem studies provide converging evidence that patients with schizophrenia have a dysregulated developmental trajectory of frontal lobe myelination. The hypothesis that typical and atypical medications may differentially impact brain myelination in adults with schizophrenia was previously assessed with inversion recovery (IR) images. Increased white matter (WM) volume suggestive of increased myelination was detected in the patient group treated with an atypical antipsychotic compared to a typical one. Objective: In a follow-up reanalysis of MRI images from the original study, we used a novel method to assess whether the difference in WM volumes could be caused by a differential effect of medications on the intracortical myelination process. Design, setting, and participants: Two different male cohorts of healthy controls ranging in age from 18-35 years were compared to cohorts of subjects with schizophrenia who were treated with either oral risperidone (Ris) or fluphenazine decanoate (Fd). Main outcome measure: A novel MRI method that combines the distinct tissue contrasts provided by IR and proton density (PD) images was used to estimate intracortical myelin (ICM) volume. Results: When compared with their pooled healthy control comparison group, the two groups of schizophrenic patients differed in the frontal lobe ICM measure with the Ris group having significantly higher volume. Conclusions: The data suggest that in adults with schizophrenia antipsychotic treatment choice may be specifically and differentially impacting later-myelinating intracortical circuitry. In vivo MRI can be used to dissect subtle differences in brain tissue characteristics and thus help clarify the effect of pharmacologic treatments on developmental and pathologic processes. (C) 2009 Elsevier B.V. All rights reserved. C1 [Bartzokis, George; Stewart, Stephanie B.; Oluwadara, Bolanle; Lucas, Andrew J.; Pantages, Joanna; Pratt, Erika; Sherin, Jonathan E.; Altshuler, Lori L.; Gitlin, Michael J.; Subotnik, Kenneth L.; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Div Brain Mapping,Lab Neuroimaging, Los Angeles, CA 90095 USA. [Bartzokis, George; Oluwadara, Bolanle; Pantages, Joanna; Pratt, Erika; Sherin, Jonathan E.; Altshuler, Lori L.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. RP Bartzokis, G (reprint author), 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NCRR NIH HHS [P41 RR013642-097338, P41 RR013642-116576, P41 RR013642-125914, P41 RR013642-107155, P41 RR013642]; NIA NIH HHS [R01 AG027342-02, AG027342, R01 AG027342, R01 AG027342-03]; NIMH NIH HHS [MH37705, P50 MH066286-029005, P50 MH066286-049005, R01 MH037705-15A1, R01 MH037705-17, R01 MH037705-19, R01 MH037705-20A1, R01 MH037705-22, R01 MH037705-24, R01 MH066029, R01 MH066029-03, R01 MH066029-05, MH6357, MH51928, MH0266029, P50 MH066286, P50 MH066286-01A19005, P50 MH066286-039005, P50 MH066286-059005, R01 MH037705, R01 MH037705-09S1, R01 MH037705-16, R01 MH037705-18, R01 MH037705-21, R01 MH037705-21S1, R01 MH037705-23, R01 MH066029-01A2, R01 MH066029-02, R01 MH066029-04] NR 112 TC 45 Z9 46 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2009 VL 113 IS 2-3 BP 322 EP 331 DI 10.1016/j.schres.2009.06.014 PG 10 WC Psychiatry SC Psychiatry GA 492CD UT WOS:000269630800026 PM 19616412 ER PT J AU Ricardo, A Szostak, JW AF Ricardo, Alonso Szostak, Jack W. TI LIFE ON EARTH SO SCIENTIFIC AMERICAN LA English DT Article C1 [Ricardo, Alonso] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Szostak, Jack W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ricardo, A (reprint author), Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. NR 6 TC 23 Z9 24 U1 5 U2 38 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 0036-8733 J9 SCI AM JI Sci.Am. PD SEP PY 2009 VL 301 IS 3 BP 54 EP 61 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 488GI UT WOS:000269336800023 PM 19708528 ER PT J AU Mochida, GH AF Mochida, Ganeshwaran H. TI Genetics and Biology of Microcephaly and Lissencephaly SO SEMINARS IN PEDIATRIC NEUROLOGY LA English DT Review AB Genetic microcephaly and lissencephaly are 2 of the most common brain malformations. Each of them is a heterogeneous group of disorders caused by mutations of many different genes. They are a significant cause of neurological morbidity in children worldwide, responsible for many cases of mental retardation, cerebral palsy, and epilepsy. Recent advances in molecular genetics have led to the identification of several genes causing these disorders, and thus accurate molecular diagnosis and improved genetic counseling has become available for many patients and their families. More recently identified genes include STIL, causing primary autosomal recessive microcephaly (microcephaly vera), and TUBA1A, causing lissencephaly. Numerous other disease genes are likely still to be identified. Functional studies of genes that cause microcephaly and lissencephaly have provided valuable insight into the molecular mechanisms of human brain development. Semin Pediatr Neurol 16: 120-126 (C) 2009 Elsevier Inc. All rights reserved. C1 [Mochida, Ganeshwaran H.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. [Mochida, Ganeshwaran H.] Massachusetts Gen Hosp, Pediat Neurol Unit, Boston, MA 02114 USA. [Mochida, Ganeshwaran H.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Mochida, Ganeshwaran H.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. RP Mochida, GH (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, 3 Blackfan Circle,CLS630, Boston, MA 02115 USA. EM gmochida@bidmc.harvard.edu FU NIH/NINDS [R37NS35129]; Dubai Harvard Foundation for Medical Research; Manton Center for Orphan Disease Research FX Supported in part by grants from NIH/NINDS (R37NS35129), the Dubai Harvard Foundation for Medical Research, and the Manton Center for Orphan Disease Research. NR 78 TC 30 Z9 31 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1071-9091 J9 SEMIN PEDIATR NEUROL JI Semin. Pediatr. Neurol. PD SEP PY 2009 VL 16 IS 3 BP 120 EP 126 DI 10.1016/j.spen.2009.07.001 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA V15GQ UT WOS:000207790900004 PM 19778709 ER PT J AU Hough, S AF Hough, Sigmund TI From the Editor SO SEXUALITY AND DISABILITY LA English DT Editorial Material C1 VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, W Roxbury, MA 02132 USA. RP Hough, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Sigmund_Hough@hms.harvard.edu NR 0 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 SEP PY 2009 VL 27 IS 3 BP 125 EP 125 DI 10.1007/s11195-009-9125-0 PG 1 WC Rehabilitation SC Rehabilitation GA 481DZ UT WOS:000268788900001 ER PT J AU Hough, S AF Hough, Sigmund TI Human Sexuality, 3rd edition SO SEXUALITY AND DISABILITY LA English DT Book Review C1 [Hough, Sigmund] VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, W Roxbury, MA 02132 USA. [Hough, Sigmund] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Hough, Sigmund] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Hough, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Sigmund_Hough@hms.harvard.edu NR 1 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 SEP PY 2009 VL 27 IS 3 BP 179 EP 180 DI 10.1007/s11195-009-9128-x PG 2 WC Rehabilitation SC Rehabilitation GA 481DZ UT WOS:000268788900007 ER PT J AU Ghebremichael, M Larsen, U Paintsil, E AF Ghebremichael, Musie Larsen, Ulla Paintsil, Elijah TI Association of Age at First Sex With HIV-1, HSV-2, and Other Sexual Transmitted Infections Among Women in Northern Tanzania SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SIMPLEX-VIRUS TYPE-2; MOSHI URBAN DISTRICT; REPRODUCTIVE HEALTH; YOUNG-WOMEN; ADOLESCENT GIRLS; ABUSE HISTORY; RISK BEHAVIOR; SOUTH-AFRICA; INTERCOURSE; TRANSMISSION AB Background: To examine the association between age at first sex and the prevalence of sexually transmitted infections (STIs), including HIV-1 and HSV-2, in women in Moshi urban district, northern Tanzania. Methods: A total of 2019 women aged 20 to 44 were randomly selected in a 2-stage sampling from Moshi urban district, northern Tanzania. Information on demographics and sexual behaviors were obtained. Blood and urine samples were drawn for testing of HIV-1, HSV-2, and other STIs. Results: Women who had their first sexual intercourse at age between 18 and 19 (OR = 0.66; 95% CI = 0.50-0.86) or 20+ (OR = 0.46; 95% CI = 0.36-0.60) were less likely to have STIs, including HIV-1 and HSV-2, than women who had their first intercourse before their 18th birthday. The hazards of having had first sex at an earlier age were significantly higher for women who tested positive for STIs (HR = 1.52; 95% CI: 1.37-1.69) or had STI symptoms (HR = 1.17; 95% CI: 1.05-1.30). Early age at first sex was associated with having a regular noncohabiting partner (HR = 1.40; 95% CI: 1.23-1.58), female circumcision (HR = 1.20; 95% CI: 1.02-1.40), and coercion at first intercourse (HR = 1.47; 95% CI: 1.15-1.89). Conclusions: In sub-Saharan Africa, where the prevalence of HIV and other STIs is high, a better understanding of the determinants of the age at first sex is crucial for HIV/STI prevention programs. Prevention programs should not only aim at delaying the age at first sex but also address factors leading to early age at first sex. C1 [Ghebremichael, Musie] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ghebremichael, Musie] Dana Farber Canc Inst, Boston, MA 02115 USA. [Larsen, Ulla] Univ Maryland, Dept Sociol, College Pk, MD 20742 USA. [Paintsil, Elijah] Yale Univ, Sch Med, Dept Pediat & Pharmacol, New Haven, CT USA. RP Ghebremichael, M (reprint author), Dana Farber Canc Ctr Inst, 3 Blackfan Circle,CLS 11045, Boston, MA 02115 USA. EM musie@jimmy.harvard.edu FU Harvard University Center for AIDS Research (CFAR) NIH [P30-AI 060354]; NIH/NICHD [R01 HD41202]; MAID [K08 A1074404] FX Supported by the Harvard University Center for AIDS Research (CFAR) NIH P30-AI 060354, NIH/NICHD R01 HD41202, and MAID K08 A1074404. NR 48 TC 15 Z9 15 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD SEP PY 2009 VL 36 IS 9 BP 570 EP 576 DI 10.1097/OLQ.0b013e3181a866b8 PG 7 WC Infectious Diseases SC Infectious Diseases GA 488TX UT WOS:000269374100007 PM 19707109 ER PT J AU Lin, HW Rho, MB Amin-Hanjani, S Barker, FG Deschler, DG AF Lin, Harrison W. Rho, Michael B. Amin-Hanjani, Sepideh Barker, Fred G., II Deschler, Daniel G. TI Glossopharyngeal and Limited Vagal Neurectomy for Cancer-Related Carotid Sinus Syncope SO SKULL BASE-AN INTERDISCIPLINARY APPROACH LA English DT Article DE Head and neck cancer; carotid sinus; syncope; glossopharyngeal neuralgia; neurectomy ID PARAPHARYNGEAL SPACE LESIONS; SURGICAL-TREATMENT; NEURALGIA; NECK; PACEMAKER; SECONDARY; TUMORS AB Head and neck cancer patients with cervical disease involving the glossopharyngeal or vagus nerves can experience dangerous cardiovascular phenomena, including carotid sinus syncope (CSS). Medical and minimally invasive interventions, including pacemaker placement, incompletely address the etiologies of syncopal episodes and therefore often provide limited benefit. The objectives of this report are to highlight the difficulties of managing cancer-related CSS, to present a highly effective surgical intervention, and to review the literature regarding the pathophysiology and treatment options for patients with cancer-related CSS. Two patients with cancer-related CSS continued to experience syncopal episodes despite medical and pacemaker therapy. Consequently, these patients underwent a suboccipital craniotomy for glossopharyngeal and limited vagal neurectomy. After surgery, both patients had uncomplicated postoperative courses with resolution of syncope. C1 [Lin, Harrison W.; Rho, Michael B.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Lin, Harrison W.; Rho, Michael B.; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Dept Neurosurg Serv, Boston, MA 02114 USA. [Amin-Hanjani, Sepideh] Univ Illinois, Dept Neurosurg, Chicago, IL USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM Daniel_Deschler@meei.harvard.edu NR 19 TC 2 Z9 2 U1 1 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1531-5010 J9 SKULL BASE-INTERD AP JI Skull Base-Interdiscip. Appr. PD SEP PY 2009 VL 19 IS 5 BP 369 EP 373 DI 10.1055/s-0029-1220204 PG 5 WC Clinical Neurology; Otorhinolaryngology; Surgery SC Neurosciences & Neurology; Otorhinolaryngology; Surgery GA 531TZ UT WOS:000272693200010 PM 20190949 ER PT J AU Armstrong, H Carter, CK Wong, KFK Kohn, R AF Armstrong, Helen Carter, Christopher K. Wong, Kin Foon Kevin Kohn, Robert TI Bayesian covariance matrix estimation using a mixture of decomposable graphical models SO STATISTICS AND COMPUTING LA English DT Article DE Covariance selection; Reduced conditional sampling; Variable selection ID CHAIN MONTE-CARLO; DISTRIBUTIONS; SELECTION; DECOMPOSITION; LIKELIHOOD; PRIORS AB We present a Bayesian approach to estimating a covariance matrix by using a prior that is a mixture over all decomposable graphs, with the probability of each graph size specified by the user and graphs of equal size assigned equal probability. Most previous approaches assume that all graphs are equally probable. We show empirically that the prior that assigns equal probability over graph sizes outperforms the prior that assigns equal probability over all graphs in more efficiently estimating the covariance matrix. The prior requires knowing the number of decomposable graphs for each graph size and we give a simulation method for estimating these counts. We also present a Markov chain Monte Carlo method for estimating the posterior distribution of the covariance matrix that is much more efficient than current methods. Both the prior and the simulation method to evaluate the prior apply generally to any decomposable graphical model. C1 [Carter, Christopher K.; Kohn, Robert] Univ New S Wales, Australian Sch Business, Sydney, NSW, Australia. [Armstrong, Helen] Univ New S Wales, Sch Math & Stat, Sydney, NSW, Australia. [Wong, Kin Foon Kevin] Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Kohn, R (reprint author), Univ New S Wales, Australian Sch Business, Sydney, NSW, Australia. EM r.kohn@unsw.edu.au RI Carter, Christopher/F-6535-2013; Wong, Kin Foon Kevin/C-7896-2014 OI Carter, Christopher/0000-0001-8949-9239; NR 34 TC 19 Z9 19 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0960-3174 EI 1573-1375 J9 STAT COMPUT JI Stat. Comput. PD SEP PY 2009 VL 19 IS 3 BP 303 EP 316 DI 10.1007/s11222-008-9093-8 PG 14 WC Computer Science, Theory & Methods; Statistics & Probability SC Computer Science; Mathematics GA 459OB UT WOS:000267111500007 ER PT J AU Maas, MB Furie, KL Lev, MH Ay, H Singhal, AB Greer, DM Harris, GJ Halpern, E Koroshetz, WJ Smith, WS AF Maas, Matthew B. Furie, Karen L. Lev, Michael H. Ay, Hakan Singhal, Aneesh B. Greer, David M. Harris, Gordon J. Halpern, Elkan Koroshetz, Walter J. Smith, Wade S. TI National Institutes of Health Stroke Scale Score Is Poorly Predictive of Proximal Occlusion in Acute Cerebral Ischemia SO STROKE LA English DT Article DE acute stroke; angiography; CT; scales ID DIFFUSION-WEIGHTED MRI; HYPERACUTE STROKE; NIHSS SCORE; TIME WINDOW; THROMBOLYSIS; PERFUSION; THERAPY; MANAGEMENT; PATIENT; BRAIN AB Background and Purpose-Multimodal imaging is gaining an important role in acute stroke. The benefit of obtaining additional clinically relevant information must be weighed against the detriment of increased cost, delaying time to treatment, and adverse events such as contrast-induced nephropathy. Use of National Institutes of Health Stroke Scale (NIHSS) score to predict a proximal arterial occlusion (PO) is suggested by several case series as a viable method of selecting cases appropriate for multimodal imaging. Methods-Six hundred ninety-nine patients enrolled in a prospective cohort study involving CT angiographic imaging in acute stroke were dichotomized according to the presence of a PO, including a subgroup of 177 subjects with middle cerebral artery M1 occlusion. Results-The median NIHSS score of patients found to have a PO was higher than the overall median (9 versus 5, P < 0.0001). The median NIHSS score of patients with middle cerebral artery M1 occlusion was 14. NIHSS score >= 10 had 81% positive predictive value for PO but only 48% sensitivity with the majority of subjects with PO presenting with lower NIHSS scores. All patients with NIHSS score >= 2 would need to undergo angiographic imaging to detect 90% of PO. Conclusions-High NIHSS score correlates with the presence of a proximal arterial occlusion in patients presenting with acute cerebral ischemia. No NIHSS score threshold can be applied to select a subgroup of patients for angiographic imaging without failing to capture the majority of cases with clinically important occlusive lesions. The finding of minimal clinical deficits should not deter urgent angiographic imaging in otherwise appropriate patients suspected of acute stroke. (Stroke. 2009;40:2988-2993.) C1 [Maas, Matthew B.; Furie, Karen L.; Singhal, Aneesh B.; Greer, David M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lev, Michael H.; Ay, Hakan; Harris, Gordon J.; Halpern, Elkan] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Maas, MB (reprint author), 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM mmaas@partners.org FU Agency for Healthcare Research and Quality [AHRQ R01 HS11392]; National Institutes of Health [P50NS051343] FX Supported by Agency for Healthcare Research and Quality grant AHRQ R01 HS11392. M. B. M. is supported by National Institutes of Health grant P50NS051343. NR 20 TC 55 Z9 56 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2009 VL 40 IS 9 BP 2988 EP 2993 DI 10.1161/STROKEAHA.109.555664 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 487BB UT WOS:000269244300010 PM 19608992 ER PT J AU Almandoz, JED Yoo, AJ Stone, MJ Schaefer, PW Goldstein, JN Rosand, J Oleinik, A Lev, MH Gonzalez, RG Romero, JM AF Almandoz, Josser E. Delgado Yoo, Albert J. Stone, Michael J. Schaefer, Pamela W. Goldstein, Joshua N. Rosand, Jonathan Oleinik, Alexandra Lev, Michael H. Gonzalez, R. Gilberto Romero, Javier M. TI Systematic Characterization of the Computed Tomography Angiography Spot Sign in Primary Intracerebral Hemorrhage Identifies Patients at Highest Risk for Hematoma Expansion The Spot Sign Score SO STROKE LA English DT Article DE CT angiography; emergency medicine; intracerebral hemorrhage; outcome ID ACTIVATED FACTOR-VII; CT ANGIOGRAPHY; CONTRAST EXTRAVASATION; MORTALITY; SAFETY AB Background and Purpose-The presence of active contrast extravasation (the spot sign) on computed tomography (CT) angiography has been recognized as a predictor of hematoma expansion in patients with intracerebral hemorrhage. We aim to systematically characterize the spot sign to identify features that are most predictive of hematoma expansion and construct a spot sign scoring system. Methods-We retrospectively reviewed CT angiograms performed in all patients who presented to our emergency department over a 9-year period with primary intracerebral hemorrhage and had a follow-up noncontrast head CT within 48 hours of the baseline CT angiogram. Three neuroradiologists reviewed the CT angiograms and determined the presence and characteristics of spot signs according to strict radiological criteria. Baseline and follow-up intracerebral hemorrhage volumes were determined by computer-assisted volumetric analysis. Results-We identified spot signs in 71 of 367 CT angiograms (19%), 6 of which were delayed spot signs (8%). The presence of any spot sign increased the risk of significant hematoma expansion (69%, OR=92, P < 0.0001). Among the spot sign characteristics examined, the presence of >= 3 spot signs, a maximum axial dimension >= 5 mm, and maximum attenuation >= 180 Hounsfield units were independent predictors of significant hematoma expansion, and these were subsequently used to construct the spot sign score. In multivariate analysis, the spot sign score was the strongest predictor of significant hematoma expansion, independent of time from ictus to CT angiogram evaluation. Conclusion-The spot sign score predicts significant hematoma expansion in primary intracerebral hemorrhage. If validated in other data sets, it could be used to select patients for early hemostatic therapy. (Stroke. 2009;40:2994-3000.) C1 [Almandoz, Josser E. Delgado; Yoo, Albert J.; Stone, Michael J.; Schaefer, Pamela W.; Lev, Michael H.; Gonzalez, R. Gilberto; Romero, Javier M.] Harvard Univ, Dept Radiol, Div Neuroradiol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Rosand, Jonathan; Oleinik, Alexandra] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Rosand, Jonathan; Oleinik, Alexandra] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. RP Almandoz, JED (reprint author), Harvard Univ, Dept Radiol, Div Neuroradiol, Massachusetts Gen Hosp,Med Sch, Gray 2,Room 273A,55 Fruit St, Boston, MA 02114 USA. EM josser.delgado@gmail.com RI Goldstein, Joshua/H-8953-2016 FU American Heart Association [0755984T] FX Supported, in part, by the American Heart Association Grant-in-Aid 0755984T. NR 13 TC 81 Z9 81 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2009 VL 40 IS 9 BP 2994 EP 3000 DI 10.1161/STROKEAHA.109.554667 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 487BB UT WOS:000269244300011 ER PT J AU Maas, MB Lev, MH Ay, H Singhal, AB Greer, DM Smith, WS Harris, GJ Halpern, E Kemmling, A Koroshetz, WJ Furie, KL AF Maas, Matthew B. Lev, Michael H. Ay, Hakan Singhal, Aneesh B. Greer, David M. Smith, Wade S. Harris, Gordon J. Halpern, Elkan Kemmling, Andre Koroshetz, Walter J. Furie, Karen L. TI Collateral Vessels on CT Angiography Predict Outcome in Acute Ischemic Stroke SO STROKE LA English DT Article DE acute stroke; angiography; collateral; outcomes ID SOURCE IMAGES; BLOOD-FLOW; INFARCT; BRAIN; TIME; MRI AB Background and Purpose-Despite the abundance of emerging multimodal imaging techniques in the field of stroke, there is a paucity of data demonstrating a strong correlation between imaging findings and clinical outcome. This study explored how proximal arterial occlusions alter flow in collateral vessels and whether occlusion or extent of collaterals correlates with prehospital symptoms of fluctuation and worsening since onset or predict in-hospital worsening. Methods-Among 741 patients enrolled in a prospective cohort study involving CT angiographic imaging in acute stroke, 134 cases with proximal middle cerebral artery occlusion and 235 control subjects with no occlusions were identified. CT angiography was used to identify occlusions and grade the extent of collateral vessels in the sylvian fissure and leptomeningeal convexity. History of symptom fluctuation or progressive worsening was obtained on admission. Results-Prehospital symptoms were unrelated to occlusion or collateral status. In cases, 37.5% imaged within 1 hour were found to have diminished collaterals versus 12.1% imaged at 12 to 24 hours (P=0.047). No difference in worsening was seen between cases and control subjects with adequate collaterals, but cases with diminished sylvian and leptomeningeal collaterals experienced greater risk of worsening compared with control subjects measured either by admission to discharge National Institutes of Health Stroke Scale increase >= 1 (55.6% versus 16.6%, P=0.001) or >= 4 (44.4% versus 6.4%, P=0.001). Conclusion-Most patients with proximal middle cerebral artery occlusion rapidly recruit sufficient collaterals and follow a clinical course similar to patients with no occlusions, but a subset with diminished collaterals is at high risk for worsening. (Stroke. 2009;40:3001-3005.) C1 [Maas, Matthew B.; Singhal, Aneesh B.; Greer, David M.; Furie, Karen L.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lev, Michael H.; Ay, Hakan; Harris, Gordon J.; Halpern, Elkan; Kemmling, Andre] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Maas, MB (reprint author), 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM mmaas@partners.org FU Agency for Healthcare Research and Quality [R01 HS11392]; National Institutes of Health [P50NS051343] FX Supported by Agency for Healthcare Research and Quality grant AHRQ R01 HS11392. M. B. M. supported by National Institutes of Health grant P50NS051343. NR 14 TC 110 Z9 117 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2009 VL 40 IS 9 BP 3001 EP 3005 DI 10.1161/STROKEAHA.109.552513 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 487BB UT WOS:000269244300012 PM 19590055 ER PT J AU van Rooden, S van der Grond, J van den Boom, R Haan, J Linn, J Greenberg, SM van Buchem, MA AF van Rooden, Sanneke van der Grond, Jeroen van den Boom, Rivka Haan, Joost Linn, Jennifer Greenberg, Steven M. van Buchem, Mark A. TI Descriptive Analysis of the Boston Criteria Applied to a Dutch-Type Cerebral Amyloid Angiopathy Population SO STROKE LA English DT Article DE cerebral amyloid angiopathy; hemorrhage; MRI; neuroradiology ID SUPERFICIAL SIDEROSIS; ALZHEIMERS-DISEASE; CLINICAL-DIAGNOSIS; HCHWA-D; HEREDITARY; HEMORRHAGE; MICROBLEEDS; AUTOPSY; LESIONS AB Background and Purpose-Validation of the Boston criteria for the in vivo diagnosis of cerebral amyloid angiopathy (CAA) is challenging, because noninvasive diagnostic tests do not exist. Hereditary cerebral hemorrhage with amyloidosis-Dutch type is an accepted monogenetic model of CAA and diagnosis can be made with certainty based on DNA analysis. The aim of this study was to analyze and refine the existing Boston criteria in patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type. Methods-We performed T2*-weighted MRI in 27 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type to assess the presence and location of microbleeds, intracranial hemorrhages, and superficial siderosis. Using the Boston criteria, subjects were categorized as having: no hemorrhages, possible CAA, probable CAA, and hemorrhagic lesions not qualifying for CAA. The sensitivity of the Boston criteria was calculated separately using intracranial hemorrhages only and using intracranial hemorrhages and microbleeds. Results-The sensitivity of the Boston criteria for probable CAA increased from 48% to 63% when microbleeds were included. For symptomatic subjects only, the sensitivity was 100%. No hemorrhages were identified in the deep white matter, basal ganglia, thalamus, or brainstem. Superficial siderosis, observed in 6 patients, did not increase the sensitivity of the Boston criteria in our study group. Conclusions-Our data show that using T2*-weighted MRI and including microbleeds increase the sensitivity of the Boston criteria. The exclusion of hemorrhages in the deep white matter, basal ganglia, thalamus, and brainstem does not lower the sensitivity of the Boston criteria. (Stroke. 2009;40:3022-3027.) C1 [van Rooden, Sanneke; van der Grond, Jeroen; van den Boom, Rivka; van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. [Haan, Joost] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands. [Haan, Joost] Rijnland Hosp, Dept Neurol, Leiderdorp, Netherlands. [Linn, Jennifer] Univ Hosp Munich, Dept Neuroradiol, Munich, Germany. [Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. RP van Rooden, S (reprint author), Leiden Univ, Med Ctr, Dept Radiol, C3-Q,POB 9600, NL-2300 RC Leiden, Netherlands. EM S.van_Rooden@lumc.nl RI Linn, Jennifer/H-8202-2013; OI Linn, Jennifer/0000-0003-0797-2761 NR 27 TC 48 Z9 49 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2009 VL 40 IS 9 BP 3022 EP 3027 DI 10.1161/STROKEAHA.109.554378 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 487BB UT WOS:000269244300016 PM 19556530 ER PT J AU Vosler, PS Graham, SH Wechsler, LR Chen, J AF Vosler, Peter S. Graham, Steven H. Wechsler, Lawrence R. Chen, Jun TI Mitochondrial Targets for Stroke Focusing Basic Science Research Toward Development of Clinically Translatable Therapeutics SO STROKE LA English DT Article DE cerebral ischemia; therapeutics; neuroprotection; mitochondria ID ISCHEMIC BRAIN-INJURY; N-TERMINAL KINASE; FOCAL CEREBRAL-ISCHEMIA; INDUCED CELL-DEATH; PEPTIDE INHIBITOR; SIGNALING PATHWAY; APOPTOSIS; AUTOPHAGY; BIOGENESIS; ACTIVATION AB Background and Purpose-Stroke is a major cause of death and disability, and it is imperative to develop therapeutics to mitigate stroke-related injury. Despite many promising prospects, attempts at translating neuroprotective agents that show success in animal models of stroke have resulted in very limited clinical success. Summary of Review-This review discusses reasons for the lack of translational success based on the therapeutic targets tested and the pathophysiology of stroke. New recanalization therapies and alternative therapeutic strategies are discussed concerning mitochondria-mediated cell death. Mitochondrial death-regulation pathways are divided into 3 categories: Upstream signaling pathways, agents that target mitochondria directly, and downstream death-execution effectors. The apoptosis signal-related kinase/c-Jun-terminal kinase pathway is used as an example to provide rationale as to why inhibiting signaling pathway upstream of mitochondrial dysfunction is a promising therapeutic approach. Finally, the mechanisms of autophagy and mitochondrial biogenesis are discussed in relation to stroke. Conclusions-Increasing evidence suggests that reperfusion is necessary for improved neurological outcomes after stroke. Development of improved recanalization methods with increased therapeutic windows will aid in improving clinical outcome. Adjunct neuroprotective interventions must also be developed to ensure maximal brain tissue salvage. Targeting prodeath signaling pathways upstream of mitochondrial damage is promising for potential clinically effective treatment. Further understanding of the roles of equilibrium of autophagy and mitochondrial biogenesis in the pathogenesis of stroke could also lead to novel therapeutics. (Stroke. 2009; 40: 3149-3155.) C1 [Vosler, Peter S.; Graham, Steven H.; Wechsler, Lawrence R.; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Chen, Jun] Fudan Univ, Sch Med, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Graham, Steven H.; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu FU NIH/NINDS [NS43802, NS45048, NS44178, NS56118, NS36736, NS37459]; NINDS NRSA [F30NS057886] FX This work was supported by NIH/NINDS grants (NS43802, NS45048, NS44178, NS56118, NS36736, and NS37459), VA Merit Reviews to J. C. and S. H. G., and a NINDS NRSA predoctoral fellowship grant to P. S. V. (F30NS057886). NR 39 TC 36 Z9 39 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2009 VL 40 IS 9 BP 3149 EP 3155 DI 10.1161/STROKEAHA.108.543769 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 487BB UT WOS:000269244300038 PM 19478227 ER PT J AU Warshaw, AL AF Warshaw, Andrew L. TI Restrictions on resident work-hours: Responses from organizations representing surgery SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,White 506, Boston, MA 02114 USA. EM swilliams7@partners.org 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 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2009 VL 146 IS 3 BP 397 EP 397 DI 10.1016/j.surg.2009.07.003 PG 1 WC Surgery SC Surgery GA 492SU UT WOS:000269680600001 ER PT J AU Pryor, HI O'Doherty, E Hart, A Owens, G Hoganson, D Vacanti, JP Masiakos, PT Sundback, CA AF Pryor, Howard I., II O'Doherty, Elisabeth Hart, Alison Owens, Gwen Hoganson, David Vacanti, Joseph P. Masiakos, Peter T. Sundback, Cathryn A. TI Poly(glycerol sebacate) films prevent postoperative adhesions and allow laparoscopic placement SO SURGERY LA English DT Article ID SMALL-BOWEL OBSTRUCTION; ABDOMINAL ADHESIONS; INTRAABDOMINAL ADHESIONS; BIORESORBABLE MEMBRANE; RISK-FACTORS; MULTICENTER; SURGERY; MORBIDITY; MORTALITY; SEPRAFILM AB Background. The objectives of this study were to evaluate the efficacy of poly(glycerol) sebacate (PGS) films for the prevention of visceroparietal peritoneal (VP) adhesions and demonstrate the ease of laparoscopic PGS film placement. Peritoneal adhesions occur in nearly 95% of all abdominal operations. VP adhesions can cause serious postoperative complications. The interposition of a barrier between damaged peritoneal areas during re-epithelialization has been shown to prevent adhesion formation. Current barrier products have serious drawbacks, including poor degradability, variable efficacy, and difficult handling characteristics. Methods. The efficacy of PGS films to prevent VP adhesions was evaluated in a rat peritoneal adhesion model. The animals were evaluated for the presence of VP adhesions at 3, 5, and 8 weeks. The laparoscopic applicability of PGS films was demonstrated by placement into a juvenile porcine abdomen using standard laparoscopic equipment and techniques. Results. A statistically significant 94% reduction in VP adhesion formation rate was observed between control animals (75%) and animals with a PGS film barrier (4.8%). PGS films were easily placed in the juvenile porcine abdomen and could be readily repositioned without material loss or tissue damage. Conclusion. PGS films possess a unique combination of properties, including biocompatibility, resorbability, and ease of handling. PGS barrier films were shown to be efficacious in reducing VP adhesions in the rat model. They also can be placed using standard laparoscopic techniques. These promising results suggest that PGS films will be effective barriers to adhesion formation for patients undergoing open and laparoscopic abdominal operations. (Surgery 2009; 146: 490-7.) C1 [Pryor, Howard I., II; O'Doherty, Elisabeth; Hart, Alison; Owens, Gwen; Hoganson, David; Vacanti, Joseph P.; Masiakos, Peter T.; Sundback, Cathryn A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Pryor, Howard I., II; Hoganson, David; Vacanti, Joseph P.; Masiakos, Peter T.] Harvard Univ, Sch Med, Dept Pediat Surg, MassGen Hosp Children, Boston, MA USA. RP Sundback, CA (reprint author), 185 Cambridge St,Suite 4-700, Boston, MA 02114 USA. EM csundback@part-ners.org OI Hoganson, David/0000-0002-8141-7793 FU NIH NRSA T32 [NIH T32DK07754-09]; MCHfC Storybook Ball FX Funded by NIH NRSA T32 grant: NIH T32DK07754-09 Research Training in Alimentary Tract Surgery (H.I.P.) and a generous gift from the MCHfC Storybook Ball (J.P.V.) NR 33 TC 9 Z9 9 U1 2 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2009 VL 146 IS 3 BP 490 EP 497 DI 10.1016/j.surg.2009.04.012 PG 8 WC Surgery SC Surgery GA 492SU UT WOS:000269680600015 PM 19715806 ER PT J AU Ehrenfeld, JM Seim, AR Berger, DL Sandberg, WS AF Ehrenfeld, Jesse M. Seim, Andreas R. Berger, David L. Sandberg, Warren S. TI Implementation of a Direct-From-Recovery-Room Discharge Pathway: A Process Improvement Effort SO SURGICAL INNOVATION LA English DT Article DE ambulatory surgery; laparoscopic cholecystectomy; patient selection; process improvement ID OUTPATIENT LAPAROSCOPIC CHOLECYSTECTOMY; AMBULATORY ANESTHESIA; PATIENT SELECTION; OPERATING-ROOM; CARE AB Background. The authors describe a process improvement effort to achieve direct-from-recovery-room discharge for elective laparoscopic cholecystectomy patients-without prior patient selection. Methods. The authors developed and implemented a new pathway, and then measured the learning curve (ie, success rate over time for direct discharge) and compared patients achieving direct discharge with patients admitted after surgery. Results. The learning curve between the first patient and steady-state performance was 56 patients. A total of 80% of patients achieved direct discharge. Directly discharged patients were younger (P < .001), had lower ASA physical status classifications (P < .005), and left the recovery room earlier in the day (P < .0001). However, elderly patients and those with high ASA scores frequently could be directly discharged from the recovery room. Conclusions. Through small team based rapid cycle process improvement, direct-from-recovery-room discharge of laparoscopic cholecystectomy patients can be achieved in an unselected patient population with a short learning curve. C1 [Ehrenfeld, Jesse M.; Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Seim, Andreas R.] Norwegian Univ Sci & Technol, Dept Comp & Informat Sci, N-7034 Trondheim, Norway. [Berger, David L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 458, Boston, MA 02114 USA. EM wsandberg@partners.org OI Ehrenfeld, Jesse/0000-0003-3427-0140 NR 24 TC 4 Z9 4 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1553-3506 J9 SURG INNOV JI Surg. Innov. PD SEP PY 2009 VL 16 IS 3 BP 258 EP 265 DI 10.1177/1553350609339169 PG 8 WC Surgery SC Surgery GA 499CU UT WOS:000270195100010 PM 19578054 ER PT J AU Ren, JQ Xu, HB Choi, JK Jenkins, BG Chen, YI AF Ren, Jiaqian Xu, Haibo Choi, Ji-Kyung Jenkins, Bruce G. Chen, Y. Iris TI Dopaminergic Response to Graded Dopamine Concentration Elicited by Four Amphetamine Doses SO SYNAPSE LA English DT Article DE DA; fMRI; phMRI; rCBV ID PHARMACOLOGICAL MRI; RAT-BRAIN; DRUG DISCRIMINATION; RECEPTOR; ANTAGONIST; CONTRAST; BOLD; D3; MICROCIRCULATION; TRANSPLANTATION AB We studied the metabolic responses to different DA concentrations elicited by four doses of D-amphetamine (AMPH, 0, 0.25, 0.5, 1.0, or 3.0 mg/kg). We compared the degree of DA release (via microdialysis) with striatal cAMP activity and whole brain maps of cerebral blood volume (rCBV) changes (via pharmacological MRI, phMRI). Results: AMPH increased DA release in the caudate/putamen (CPu) and cAMP activity in the CPu, nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) in a linear dose-dependent manner (P < 0.0001). The cAMP data suggest that, postsynaptically, signal transduction induced by D1 receptor is stronger than that of D2 receptor at the higher doses (1-3 mg/kg). phMRI showed that, while higher doses of AMPH (3 mg/kg (n = 7) and 1 mg/kg (n = 6)) induced significant rCBV increases in the CPu and NAc, the degree of rCBV increase was much smaller with AMPH of 0.5 mg/kg (n = 6). In contrast, AMPH of 0.25 mg/kg (n = 8) induced significant rCBV decreases in the anteromedial CPu and NAc. The sign switch of rCBV in response to AMPH from low to high doses likely reflects the switching in the balance of D2/D3 stimulation vs. D1/D5 stimulation. In conclusion, degree of postsynaptic signal transduction is linearly correlated to the extracellular DA concentration. However, the presynaptic binding may dominate the overall DA innervation at the lower range of DA concentration. Synapse 63:764-772, 2009. (C)2009 Wiley-Liss, Inc. C1 [Ren, Jiaqian; Choi, Ji-Kyung; Jenkins, Bruce G.; Chen, Y. Iris] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA USA. [Xu, Haibo] Union Hosp, Wuhan, Peoples R China. RP Chen, YI (reprint author), Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM iris@nmr.mgh.harvard.edu FU NIDA [5R01 DA16187-05]; NCCAM [P01 AT002048] FX NIDA; Contract grant number: 5R01 DA16187-05; Contract grant sponsor: NCCAM; Contract grant number: P01 AT002048. NR 40 TC 26 Z9 26 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP PY 2009 VL 63 IS 9 BP 764 EP 772 DI 10.1002/syn.20659 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 472KI UT WOS:000268129100006 PM 19484725 ER PT J AU Zhai, R Sheu, CC Su, L Gong, MN Tejera, P Chen, F Wang, Z Convery, MP Thompson, BT Christiani, DC AF Zhai, R. Sheu, C. C. Su, L. Gong, M. N. Tejera, P. Chen, F. Wang, Z. Convery, M. P. Thompson, B. T. Christiani, D. C. TI Serum bilirubin levels on ICU admission are associated with ARDS development and mortality in sepsis SO THORAX LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; INTENSIVE-CARE-UNIT; UDP-GLUCURONOSYLTRANSFERASES; HEPATIC-DYSFUNCTION; ORGAN FAILURE; RISK-FACTOR; UGT1A1-ASTERISK-28; POLYMORPHISMS; TOXICITY AB Background: Hyperbilirubinaemia is a common complication of sepsis. Elevated bilirubin may induce inflammation and apoptosis. It was hypothesised that increased serum bilirubin on Intensive Care Unit (ICU) admission contributes to sepsis-related acute respiratory distress syndrome (ARDS). Methods: Serum bilirubin on ICU admission was measured in 1006 patients with sepsis. Serial serum bilirubin was analysed prospectively in patients with sepsis who had ARDS for a period of 28 days. The effects of clinical factors and variants of the UGT1A1 gene on serum bilirubin levels were determined. Outcomes were ARDS risk and mortality. Results: During 60-day follow-up, 326 patients with sepsis developed ARDS, of whom 144 died from ARDS. The hyperbilirubinaemia (>= 2.0 mg/dl) rate in patients with ARDS (22.4%) was higher than in those without ARDS (14.1%, p = 0.002). For each 1.0 mg/dl increase in admission bilirubin, ARDS risk and 28- and 60-day ARDS mortalities were increased by 7% (OR = 1.07; p = 0.003), 20% (OR = 1.20; p = 0.002) and 18% (OR = 1.18; p = 0.004), respectively. Compared with subjects with bilirubin levels <2.0 mg/dl, patients with hyperbilirubinaemia had higher risks of ARDS (OR = 2.12; p = 0.0007) and 28-day (OR = 2.24; p = 0.020) and 60-day ARDS mortalities (OR = 2.09; p = 0.020). In sepsis-related ARDS, serial bilirubin levels in non-survivors were consistently higher than in survivors (p<0.0001). Clinical variables explained 29.5% of the interindividual variation in bilirubin levels, whereas genetic variants of UGT1A1 contributed 7.5%. Conclusion: In sepsis, a higher serum bilirubin level on ICU admission is associated with subsequent ARDS development and mortality. C1 [Zhai, R.; Sheu, C. C.; Su, L.; Tejera, P.; Chen, F.; Wang, Z.; Convery, M. P.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Gong, M. N.] Mt Sinai Sch Med, Dept Med, Div Pulm & Crit Care Med, New York, NY USA. [Thompson, B. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Institute of Health [HL60710, ES00002]; Flight Attendant Medical Research Institute [062459_YCSA] FX This work was supported by grants from the National Institute of Health (HL60710 and ES00002) and the Flight Attendant Medical Research Institute (FAMRI, 062459_YCSA). NR 37 TC 23 Z9 25 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD SEP PY 2009 VL 64 IS 9 BP 784 EP 790 DI 10.1136/thx.2009.113464 PG 7 WC Respiratory System SC Respiratory System GA 488QT UT WOS:000269365500012 PM 19482841 ER PT J AU Ehrenkranz, J Davies, TF AF Ehrenkranz, Joel Davies, Terry F. TI Why the History of Thyroid Disease Is Important SO THYROID LA English DT Editorial Material ID HORMONE; HYPERTHYROIDISM; INTERVIEW; THYROTROPIN; METABOLISM; IODINE; MD C1 [Ehrenkranz, Joel] Intermt Hlth Care, Murrary, UT 84093 USA. [Davies, Terry F.] Mt Sinai Hosp, Mt Sinai Sch Med, New York, NY 10029 USA. [Davies, Terry F.] James J Peters VA Med Ctr, New York, NY USA. RP Ehrenkranz, J (reprint author), Intermt Hlth Care, 5121 Cottonwood St, Murrary, UT 84093 USA. EM joel.ehrenkranz@imail.org NR 35 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 1050-7256 J9 THYROID JI Thyroid PD SEP PY 2009 VL 19 IS 9 BP 929 EP 931 DI 10.1089/thy.2009.1588 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491KP UT WOS:000269577900002 PM 19731975 ER PT J AU Davies, TF Bianco, AC AF Davies, Terry F. Bianco, Antonio C. TI Dr. John Maxwell "Max'' McKenzie (1928-2009) In Memoriam SO THYROID LA English DT Biographical-Item C1 [Davies, Terry F.] Mt Sinai Hosp, Mt Sinai Sch Med, New York, NY 10029 USA. [Davies, Terry F.] James J Peters VA Med Ctr, New York, NY USA. [Bianco, Antonio C.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. RP Davies, TF (reprint author), Mt Sinai Hosp, Mt Sinai Sch Med, New York, NY 10029 USA. RI Bianco, Antonio/A-4965-2008 OI Bianco, Antonio/0000-0001-7737-6813 NR 0 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD SEP PY 2009 VL 19 IS 9 BP 1023 EP 1023 DI 10.1089/thy.2009.1587 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491KP UT WOS:000269577900020 ER PT J AU Moonsamy, P Bonella, P Goodwin, G Dolan, L Erlich, HA AF Moonsamy, P. Bonella, P. Goodwin, G. Dolan, L. Erlich, H. A. CA TIDGC TI The identification of a new HLA-DPB1 allele (*1302) in one family and the detection of a recombination event between the DR and the DQ regions in another Caucasian T1DGC family SO TISSUE ANTIGENS LA English DT Article DE HLA-DPB1; SSOP linear array assay; Mendelian inheritance; recombination event AB The analysis of families collected by the T1DGC and typed at high resolution for the HLA class I and class II loci provided an opportunity for identifying new alleles and rare recombination events. In one American Caucasian family, a novel allele (HLA-DPB1*1302), detected as an unusual pattern of probe binding, was identified in the mother and in one child. Amplicons from both individuals were sequenced and a new variant of DPB1*1301 with an A-> T mutation [TAC to TTC in codon 64, (amino acid 35); Y to F] was confirmed. In another American Caucasian family, one child inherited an unusual haplotype, DRB1*1501-DQA1*0102-DQB1*0609-DPA1*0103-DPB1*0601 resulting from a recombination between the DRB1 loci on the maternal chromosomes DRB1*1501-DQA1*0102-DQB1*0602-DPA1*0103-DPB1*0401 and DRB1*1302-DQA1*0102-DQB1*0609-DPA1*0103-DPB1*0601. C1 [Moonsamy, P.; Erlich, H. A.] Roche Mol Syst Inc, Human Genet, Pleasanton, CA 94588 USA. [Bonella, P.; Erlich, H. A.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Goodwin, G.] Harvard Univ, Joslin Diabet Ctr, Cambridge, MA 02138 USA. [Dolan, L.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. RP Moonsamy, P (reprint author), Roche Mol Syst Inc, Human Genet, 4300 Hacienda Dr, Pleasanton, CA 94588 USA. EM priscilla.moonsamy@roche.com FU National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); Children's Hospital Oakland Research Institute FX This research utilizes resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD) and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418.The authors also like to acknowledge J. Noble from the Children's Hospital Oakland Research Institute for her advise and support, L.G. Bentley of Roche Molecular systems Sequencing Group for sequencing the new DPB1 allele, J.L. Post for the development of the StripScan software, Wolfgang Helmberg for the development of the SCORE software, Jeralynn Wodehouse for administrative advice, HLA Group at Roche Molecular Systems for support and Sean Boyle's Linear Array Scale Up Group at Roche Molecular Systems for DPB1 assay production. NR 1 TC 3 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD SEP PY 2009 VL 74 IS 3 BP 269 EP 270 DI 10.1111/j.1399-0039.2009.01308.x PG 2 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 480EE UT WOS:000268714200024 PM 19691641 ER PT J AU Weinand, C Gupta, R Weinberg, E Madisch, I Neville, CM Jupiter, JB Vacanti, JP AF Weinand, Christian Gupta, Rajiv Weinberg, Eli Madisch, Ijad Neville, Craig M. Jupiter, Jesse B. Vacanti, Joseph P. TI Toward Regenerating a Human Thumb In Situ SO TISSUE ENGINEERING PART A LA English DT Article ID MESENCHYMAL STEM-CELLS; TISSUE-ENGINEERED BONE; NEURITE EXTENSION; SCAFFOLD; TRANSPLANTATION; MARROW; CARTILAGE; SYSTEM; GROWTH; RECONSTRUCTION AB Regenerative technology promises to alleviate the problem of limited donor supply for bone or organ transplants. Most expensive and time consuming is cell expansion in laboratories. We propose a method of magnetically enriched osteoprogenitor stem cells, dispersed in self-assembling hydrogels and applied onto new ultra-high-resolution, jet-based, three-dimensional printing of living human bone in a single-step for in situ bone regeneration. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were enriched with CD 117(+) cells, dispersed in different collagen I and RAD 16I hydrogel mixes, and applied onto three-dimensional printed beta-tricalcium phosphate/poly(lactic-co-glycolic acid) scaffolds, printed from ultra-high-resolution volumetric CT images of a human thumb. Constructs were directly implanted subcutaneously into nude mice for 6 weeks. In vivo radiographic volumetric CT scanning and histological evaluations were performed at 1, 2, 4, and 6 weeks, and expression of bone-specific genes and biomechanical compression testing at 6 weeks endpoint. Time-dependant accumulation of bone-like extracellular matrix was most evident in CD 117(+) hBMSCs using collagen I/RAD 16I hydrogel mix. This was shown histologically by Toluidine blue, von Kossa, and alkaline phosphatase staining, paralleled by increased radiological densities within implants approximating that of human bone, and confirmed by high expression of bone-specific osteonectin and biomechanical stiffness at 6 weeks. Human origin of newly formed tissue was established by expression of human GAPDH using RT-PCR. Statistical analysis confirmed high correlations between biomechanical stiffness, radiological densities, and bone markers. Bone tissue can be successfully regenerated in vivo using a single-step procedure with constructs composed of RAD 16I/collagen I hydrogel, CD 117(+)-enriched hBMSCs, and porous beta-tricalcium phosphate/poly(lactic-co-glycolic acid) scaffolds. C1 [Weinand, Christian; Neville, Craig M.; Vacanti, Joseph P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. [Gupta, Rajiv; Madisch, Ijad] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Weinberg, Eli] MIT, Cambridge, MA 02139 USA. [Jupiter, Jesse B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, 55 Fruit St, Boston, MA 02114 USA. EM jvacanti@partners.org FU Department of Surgery, Massachusetts General Hospital FX This study was funded by a Departmental Grant from the Department of Surgery, Massachusetts General Hospital. We would like to thank Dr. Frederic S. Shapiro, Children's Hospital, Boston, for the histopathological evaluation. NR 53 TC 7 Z9 13 U1 1 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP PY 2009 VL 15 IS 9 BP 2605 EP 2615 DI 10.1089/ten.tea.2008.0467 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 486TO UT WOS:000269221400026 PM 19199577 ER PT J AU Shaikh, S Gatzos, L Schott, DM Kao, G AF Shaikh, S. Gatzos, L. Schott, D. M. Kao, G. TI Correlation of CFU assays and CD34+Enumeration Using Single or Double-Platform Methods in Post-Thaw Cord Blood Samples SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Shaikh, S.] BIDMC, Boston, MA USA. [Gatzos, L.; Schott, D. M.; Kao, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM sshaikh1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 22A EP 23A PG 2 WC Hematology SC Hematology GA 490XU UT WOS:000269542200057 ER PT J AU Shaikh, S Kaufman, RM Jardim, GM Hwang, DG Hirsch, MS Milford, EL Clavijo, OP Lerou, P Babic, AM AF Shaikh, S. Kaufman, R. M. Jardim, G. M. Hwang, D. G. Hirsch, M. S. Milford, E. L. Clavijo, O. P. Lerou, P. Babic, A. M. TI Blood Chimerism in Monochorionic Twins: An Unusual Cause of ABO Discrepancy SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Shaikh, S.] BIDMC, Boston, MA USA. [Kaufman, R. M.; Jardim, G. M.; Hwang, D. G.; Hirsch, M. S.; Milford, E. L.; Clavijo, O. P.; Lerou, P.; Babic, A. M.] BWH, Boston, MA USA. EM sshaikh1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 114A EP 114A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200287 ER PT J AU Joo, MJ Au, DH Lee, TA AF Joo, Min J. Au, David H. Lee, Todd A. TI Use of spirometry in the diagnosis of chronic obstructive pulmonary disease and efforts to improve quality of care SO TRANSLATIONAL RESEARCH LA English DT Article ID INHALED CORTICOSTEROID USE; LUNG-FUNCTION; SALMETEROL/FLUTICASONE PROPIONATE; FLUTICASONE PROPIONATE; GEOGRAPHIC-VARIATION; ACUTE EXACERBATION; RANDOMIZED-TRIAL; AIR-FLOW; COPD; SALMETEROL AB Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not fully reversible. In a patient presenting with respiratory symptoms and risk factors, the recommendation is to perform spirometry to determine the presence of airflow obstruction. However, only about a third of patients with a diagnosis of COPD have spirometry along with their diagnosis, although studies have shown that history and physical examination alone are neither sensitive nor specific for diagnosing COPD. Thus, in current practice, many health care providers continue to diagnose and manage COPD without an accurate diagnosis and assessment of severity based on spirometry. This can contribute to inconsistent care and outcomes, as evidenced by findings of variation in spirometry use and acute exacerbation rates of COPD across geographic regions. As there is increasing evidence that pharmacotherapy for COPD has associated risks, including poor cardiovascular outcomes and pneumonia, it is pertinent to obtain an accurate diagnosis to determine appropriate risk-benefit ratios. Previous studies have shown that spirometry has an impact on COPD management; however, there seem to be barriers to the use of spirometry at the patient, provider, and health system level. Innovative quality improvement approaches, such as the application of the various components of the Chronic Care Model, could improve spirometry use in COPD. Only with accurate diagnosis can appropriate management and evidence-based treatment strategies be applied in practice. Therefore, it is important that we continue efforts to increase the use of spirometry in the diagnosis of COPD. (Translational Research 2009; 154:103-110) C1 Hines VA Hosp, CMC3, Hines, IL USA. Jesse Brown VA Hosp, CMC3, Chicago, IL USA. Univ Illinois, Dept Med, Sect Pulm Crit Care & Sleep Med, Chicago, IL USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. Univ Illinois, Dept Pharm Practice, Ctr Pharmacoecon Res, Chicago, IL USA. RP Joo, MJ (reprint author), 840 S Wood St,M-C 719, Chicago, IL 60612 USA. EM joo@uic.edu NR 70 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-5244 J9 TRANSL RES JI Transl. Res. PD SEP PY 2009 VL 154 IS 3 BP 103 EP 110 DI 10.1016/j.trsl.2009.06.003 PG 8 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 486XZ UT WOS:000269235600001 PM 19665686 ER PT J AU Souza, FF Otero, HJ Erturk, M Rybicki, FJ Ramaiya, N van den Abbeele, AD Di Salvo, DN AF Souza, Frederic F. Otero, Hansel J. Erturk, Mehmet Rybicki, Frank J. Ramaiya, Nikhil van den Abbeele, Annick D. Di Salvo, Donald N. TI Venous Thrombosis in an Outpatient Oncologic Center Distribution, Type, and Comorbidities SO ULTRASOUND QUARTERLY LA English DT Article DE venous thrombosis; pulmonary embolism; central venous catheter; DVT; superficial venous thrombosis AB Purpose: To examine outpatient oncologic patients with venous thrombosis (VT) and correlate ultrasound findings with clinical characteristics and outcome. Materials and Methods: A retrospective study of 76 patients who had upper- and lower-extremity ultrasound examinations positive for VT formed the population, drawn from a total of 509 patients who presented over a 24-month period for non-invasive imaging. Clinical indication, demographics, sonographic findings, comorbidities, and development of pulmonary embolism in these patients were recorded. The Fisher-Freeman-Halton exact test was used to determine if test characteristics varied according to the location of VT (upper or lower extremity), the level of lower-extremity thrombosis (above the knee, below the knee, or both), the presence of active disease or remission, the chronicity or acuteness of thrombosis, and the presence of a central venous catheter (CVC). Results: In the study group, 64 patients had deep VT, and 12 had superficial VT. The most prevalent tumors in our study population were lymphoma and breast and lung cancers. The most common symptoms were swelling, pain, and erythema. Whereas 61 patients had active disease, 18 patients were in remission at the time of examination. Among 30 patients with upper-extremity VT, 18 had CVCs. Venous thrombosis involved the vessel containing the central venous line in 66% of studies. Pulmonary embolism developed in 8 patients who had lower-extremity VT despite an initiation of anticoagulation therapy. Patients with thrombus in the lower extremity had higher chance to develop pulmonary embolism, but there was no significant statistical difference in the level of lower-extremity thrombosis (above the knee, below the knee, or both), disease activity, and chronicity of thrombosis. Conclusions: Venous thrombosis is most commonly acute and involves the lower extremity and the deep venous system above the knee. When VT involves the upper extremity, it is usually associated with a CVC. Pulmonary embolism is almost exclusively associated with lower-extremity VT and can occur despite anticoagulation therapy. C1 [Souza, Frederic F.; Otero, Hansel J.; Ramaiya, Nikhil; van den Abbeele, Annick D.; Di Salvo, Donald N.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Souza, Frederic F.; Otero, Hansel J.; Erturk, Mehmet; Rybicki, Frank J.; Di Salvo, Donald N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Souza, FF (reprint author), Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02115 USA. EM ffsouza@partners.org FU Toshiba; Siemens; Bracco; Pfizer; Novartis FX Dr Rybicki has disclosed that he was/is a recipient of grant/research funds from Toshiba, Siemens, and Bracco; and was/is on the speakers' bureau of Toshiba, Siemens, and Bracco.; Dr Van den Abbeele has disclosed that she was/is a recipient of grant/research funds from Pfizer and Novartis. NR 22 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-8771 J9 ULTRASOUND Q JI Ultrasound Q. PD SEP PY 2009 VL 25 IS 3 BP 145 EP 150 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V20FY UT WOS:000208127100007 PM 19730077 ER PT J AU Ignatoff, JA Chen, YH Greenberg, RE Pow-Sang, JM Messing, EM Wilding, G AF Ignatoff, Jeffrey A. Chen, Yu-Hui Greenberg, Richard Evan Pow-Sang, Julio M. Messing, Edward M. Wilding, George TI Phase II study of intravesical therapy with AD32 in patients with papillary urothelial carcinoma or carcinoma in situ (CIS) refractory to prior therapy with bacillus Calmette-Guerin (E3897): A trial of the Eastern Cooperative Oncology Group SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE AD32; Superficial transitional cell carcinoma; Urothelial carcinoma; Carcinoma in situ; Bladder; Intravesical ID SUPERFICIAL BLADDER-CANCER; TRANSITIONAL-CELL CARCINOMA; N-TRIFLUOROACETYLADRIAMYCIN-14-VALERATE AD-32; MANAGEMENT; IMMUNOTHERAPY; INSTILLATION; ADRIAMYCIN; TOXICITY; ANALOG AB Objective: To assess the safety and effectiveness of AD32, a doxorubicin analogue with little systemic exposure when administered intravesically, in patients with recurrent or refractory superficial urothelial carcinoma (formerly called transitional cell carcinoma [TCC]), or carcinoma in situ (CIS), who have failed prior BCG-based immunotherapy. Methods: Eligible patients received six weekly doses (800 mg) of intravesical AD32 and Were evaluated at 12-week intervals for 24 months or until date of worsening disease. Primary analysis was the proportion of all patients recurrence-free at 12 months. Treatment-related and GU-specific toxicities were also examined. AM participating institutions submitted the protocol for Institutional Review Board (IRB) approval. Results: The study was halted due to unavailability of study drug after accrual of 48 of a planned 64 patients; 42 were included in the analysis. Of these, 28 (67%) were still alive after median follow-up of 61.1 months. Of 21 TCC patients, 18 (85.7%) experienced disease recurrence (median time to recurrence, 5.3 months). Of the 5 CIS patients with complete response (CR), 3 (60%) experienced disease recurrence; (median time to recurrence, 37.3 months). Recurrence-free rates at 12 and 24 months were 20% (90% Cl, 7.8%, 36.1%) and 15% (90 Cl, 4.9% 30.2%), respectively, for patients with TCC and 80% (90% Cl, 31.4%, 95.8%) at both intervals for CIS patients with CR. Infection was the most common treatment-related toxicity; no grade 4 or higher toxicity was observed. The most common GU-specific toxicity was increased frequency/urgency. Conclusions: AD32 is safe and active for treatment of recurrent or refractory superficial bladder carcinoma. The agent awaits more complete characterization when drug production problems can be solved. (C) 2009 Elsevier Inc. All rights reserved. C1 [Ignatoff, Jeffrey A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Boston, MA 02115 USA. [Greenberg, Richard Evan] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Pow-Sang, Julio M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Messing, Edward M.] Univ Rochester, Rochester, NY 14627 USA. [Wilding, George] Univ Wisconsin, Madison, WI 53706 USA. RP Ignatoff, JA (reprint author), Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. EM jmi917@aol.com FU Public Health Service [CA23318, CA66636, CA21115, CA27525, CA11083, CA17145, CA21076]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D.) and supported in part by Public Health Service grants CA23318, CA66636, CA21115, CA27525, CA11083, CA17145, CA21076 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely die responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 25 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD SEP-OCT PY 2009 VL 27 IS 5 BP 496 EP 501 DI 10.1016/j.urolonc.2008.05.004 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 494MF UT WOS:000269816700006 PM 18639470 ER PT J AU Ramsey, SD Zeliadt, SB Arora, NK Potosky, AL Blough, DK Hamilton, AS Van Den Eeden, SK Oakley-Girvan, I Penson, DF AF Ramsey, Scott D. Zeliadt, Steven B. Arora, Neeraj K. Potosky, Arnold L. Blough, David K. Hamilton, Ann S. Van Den Eeden, Stephen K. Oakley-Girvan, Ingrid Penson, David F. TI Access to Information Sources and Treatment Considerations Among Men With Local Stage Prostate Cancer SO UROLOGY LA English DT Article ID EDUCATION MATERIALS; SEEKING BEHAVIORS; NEEDS; PREFERENCES; CARCINOMA; PARTNERS; DECISION; INTERNET AB OBJECTIVES To determine the role of information sources in the treatment decision-making process of men diagnosed with local stage prostate cancer. Diagnosed men have access to a large number of information sources about therapy, including print and broadcast media, the Internet, books, and friends with the disease. METHODS Prospective survey of men with local stage prostate cancer in 3 geographically separate regions was carried out. Most men were surveyed after diagnosis but before starting therapy. RESULTS On average, men with local prostate cancer consulted nearly 5 separate sources of information before treatment. The most common source of information was the patient's physician (97%), followed by lay-literature (pamphlets, videos) (76%), other health professionals (71%), friends with prostate cancer (67%), and the Internet (58%). Most men rated the Sources they consulted as helpful. Consulting the Internet was associated with considering more treatment options. Several information sources were significantly associated with considering particular treatments, but the magnitude of association was small in relation to patient age, comorbidity, and Gleason score. More than 70% of men stated that they were considering or planning only one type of therapy. CONCLUSIONS Men with local stage prostate cancer consult a wide range of information sources. Nonphysician information sources appear to influence their treatment considerations, but to a smaller degree than clinical factors. UROLOGY 74: 509-516, 2009. (C) 2009 Elsevier Inc. C1 [Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Canc Control Program, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Kaiser Permanente, Div Res, Oakland, CA USA. No Calif Canc Cctr, Fremont, CA USA. Univ So Calif, Dept Urol, Norris Canc Ctr, Los Angeles, CA USA. Univ So Calif, Dept Prevent Med, Norris Canc Ctr, Los Angeles, CA 90089 USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M3-B232, Seattle, WA 98109 USA. EM sramsey@fhcrc.org FU National Cancer Institute [N01-PC-35142, N01-PC-35139, N01-PC-35136]; Cancer Surveillance System; Fred Hutchinson Cancer Research Center [N01-PC-35142] FX Supported by the National Cancer Institute contracts N01-PC-35142, N01-PC-35139, and N01-PC-35136 and by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, which is funded by Contract No. N01-PC-35142 from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute with additional support from the Fred Hutchinson Cancer Research Center and the State of Washington. NR 25 TC 18 Z9 18 U1 1 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 SEP PY 2009 VL 74 IS 3 BP 509 EP 515 DI 10.1016/j.urology.2009.01.090 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 499GU UT WOS:000270207100011 PM 19589564 ER PT J AU Dahl, DM Ko, DSC AF Dahl, Douglas M. Ko, Dicken S. C. TI Laparoscopic Radical Prostatectomy in Renal Transplant Recipients EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material C1 [Dahl, Douglas M.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Ko, Dicken S. C.] Massachusetts Gen Hosp, Renal Transplantat Unit, Boston, MA 02114 USA. RP Dahl, DM (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD SEP PY 2009 VL 74 IS 3 BP 687 EP 687 DI 10.1016/j.urology.2009.04.054 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 499GU UT WOS:000270207100073 PM 19716928 ER PT J AU Pickel, H Reich, O Winter, R Young, RH AF Pickel, Hellmuth Reich, Olaf Winter, Raimund Young, Robert H. TI Hermann Lebert (1813-1878): a pioneer of diagnostic pathology SO VIRCHOWS ARCHIV LA English DT Biographical-Item DE Pathologist; Microscopy; Cytology; Pathologic atlas AB Hermann Lebert (1813-1879) was a pioneer of diagnostic pathology and medical iconography. He was born in Breslau, then Prussia, and died in Nice (France). He lived in Switzerland as a general physician, in France as a pathologist, and eventually became the chairman for internal medicine in Zurich and Breslau, respectively. The significance of Hermann Lebert for medical posterity has three aspects: firstly, scientific linking of the French (Parisian) school and its distinctive clinical/practical orientation to the later clinical/pathological German school of Johann Lukas Schonlein, Johannes Muller, and Rudolf Virchow; secondly, his pioneering of the diagnostic use of the microscope in pathological anatomy; and finally, his remarkable book, Trait, d'anatomie pathologique g,n,rale et sp,ciale, which has almost fallen into oblivion, being unknown to most contemporary workers. C1 [Pickel, Hellmuth; Reich, Olaf; Winter, Raimund] Med Univ Graz, Dept Gynecol, A-8036 Graz, Austria. [Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Pickel, H (reprint author), Med Univ Graz, Dept Gynecol, Auenbruggerpl 14, A-8036 Graz, Austria. EM ulli.pickel@aon.at NR 0 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD SEP PY 2009 VL 455 IS 3 BP 301 EP 305 DI 10.1007/s00428-009-0820-0 PG 5 WC Pathology SC Pathology GA 495BR UT WOS:000269864700012 PM 19688221 ER PT J AU Miller, ET Marsh, RH Harris, NS AF Miller, Evan T. Marsh, Regan H. Harris, N. Stuart TI Rabies Exposure-Implications for Wilderness Travelers SO WILDERNESS & ENVIRONMENTAL MEDICINE LA English DT Article DE rabies; Gray fox; wild animals; animal bite; wilderness medicine ID UNITED-STATES; PROPHYLAXIS; EPIDEMIOLOGY; SURVEILLANCE; PREVENTION; INDUCTION; HUMANS; COMA AB Rabies is a preventable, fatal infectious disease. Successful vaccination programs for domestic animals in developed countries have drastically decreased the risk of exposure to rabies. Yet awareness of rabies needs to remain high as important reservoirs still exist in our backyards, the wilderness, and abroad. Recognizing the risk before and after a potential exposure, so that appropriate medical care can be sought, is critical to preventing a fatal complication. This case report involves an exposure of a medical student to an ill-appearing and likely rabid gray fox in the Gila Wilderness Area of New Mexico. The student was a member of a 28-day wilderness medicine course taught by the National Outdoor Leadership School/Wilderness Medicine Institute in collaboration with the Harvard Affiliated Emergency Medicine Residency. On the first night in the field, the student awoke to a gray fox biting his foot through his sleeping bag in the early morning hours. Subsequently the student was evacuated for medical evaluation. Further care consisted of rabies postexposure prophylaxis, including thorough wound cleansing, injection of human rabies immunoglobulin, and initiation of a rabies vaccination schedule. Immediate wound care with soap and water and a viricidal agent is of utmost importance for any animal bite, but especially so in the prevention of rabies. Indications for rabies prophylaxis are complex and require prompt evaluation by a medical professional and consultation with local epidemiology to guide treatment. C1 [Miller, Evan T.] Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. [Marsh, Regan H.] Brigham & Womans & Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA USA. [Harris, N. Stuart] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Harris, N. Stuart] Harvard Univ, Sch Med, Boston, MA USA. RP Miller, ET (reprint author), Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. EM evtmille@gmail.com NR 30 TC 1 Z9 1 U1 2 U2 5 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1080-6032 J9 WILD ENVIRON MED JI Wildern. Environ. Med. PD FAL PY 2009 VL 20 IS 3 BP 290 EP 296 PG 7 WC Public, Environmental & Occupational Health; Sport Sciences SC Public, Environmental & Occupational Health; Sport Sciences GA 500HF UT WOS:000270288800015 PM 19737032 ER PT J AU Olson, JM Raugi, GJ Nguyen, VQ Yu, O Reiber, GE AF Olson, Jonathan M. Raugi, Gregory J. Nguyen, Viet Q. Yu, Onchee Reiber, Gayle E. TI Guideline concordant venous ulcer care predicts healing in a tertiary care Veterans Affairs Medical Center SO WOUND REPAIR AND REGENERATION LA English DT Article ID QUALITY-OF-LIFE; LEG ULCERS; INSUFFICIENCY AB This study describes the impact of 80% adherence to guideline concordant care for compression therapy, moist wound-healing environment, and debridement on venous ulcer outcomes. The retrospective cohort design included patients from a tertiary care Veterans Affairs Medical Center from October 2003 to September 2007. During this 5-year interval, 155 patients with 400 venous ulcers met study inclusion. A majority of ulcers (n=362) healed, with an average time to healing of 18.1 weeks (range 2-209 weeks, median 10.4 weeks). From the multivariate Poisson regression, the likelihood of ulcer healing increased when compression therapy was provided during at least 80% of visits (relative risk [RR], 1.93; 95% confidence interval [CI], 1.27-2.92) or when a moist wound-healing environment was provided during at least 80% of visits (RR, 1.63; 95% CI, 1.09-2.42). Debridement alone was not significantly associated with ulcer healing (RR, 1.0; 95% CI, 0.61-1.64). Patients who received all three treatments during at least 80% of their visits were more likely to heal than those who received < 80% treatment (RR, 2.52; 95% CI, 1.53-4.16). Guideline concordant venous ulcer care was significantly associated with venous ulcer healing, when provided at 80% or more of patient visits. C1 [Reiber, Gayle E.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Yu, Onchee] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Nguyen, Viet Q.] Univ Washington, Sch Med, Seattle, WA USA. [Raugi, Gregory J.] VA Puget Sound Healthcare Syst, Div Dermatol, Dept Vet Affairs, Seattle, WA USA. [Olson, Jonathan M.; Raugi, Gregory J.; Nguyen, Viet Q.; Reiber, Gayle E.] Hlth Serv Res & Dev, Dept Vet Affairs, Seattle, WA USA. RP Reiber, GE (reprint author), VA HSR&D, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM greiber@u.washington.edu FU Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development Service; Rehabilitation Research and Development Service FX The research reported here was supported by Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, and Rehabilitation Research and Development Service. NR 18 TC 7 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD SEP-OCT PY 2009 VL 17 IS 5 BP 666 EP 670 DI 10.1111/j.1524-475X.2009.00524.x PG 5 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 493JM UT WOS:000269732700005 PM 19769720 ER PT J AU Lipsky, BA Polis, AB Lantz, KC Norquist, JM Abramson, MA AF Lipsky, Benjamin A. Polis, Adam B. Lantz, Keith C. Norquist, Josephine M. Abramson, Murray A. TI The value of a wound score for diabetic foot infections in predicting treatment outcome: A prospective analysis from the SIDESTEP trial SO WOUND REPAIR AND REGENERATION LA English DT Article ID CLASSIFICATION-SYSTEM; ULCER CLASSIFICATION; VALIDATION; MULTICENTER; ISCHEMIA; RISK AB Scoring the severity of a diabetic foot wound infection may help assess the severity, determine the type and urgency of antibiotic and surgical treatment needed, and predict clinical outcomes. We developed a 10-item diabetic foot infection wound score (results could range from 3 to 49 [least to most severe]) incorporating semi-quantitative grading of both wound measurements and various infection parameters. Using data from a prospective diabetic foot infection antibiotic trial (SIDESTEP), we evaluated the score's accuracy in predicting outcome, analyzed its components and tested it for consistency, construct, and validity. Wound scores for 371 patients significantly correlated with the clinical response; it was favorable at the follow-up assessment in 94.8% with a baseline score < 12 compared with 77.0% with a score > 19. Scores demonstrated good internal consistency (Cronbach's alpha > 0.70 to < 0.95). Patients with more severe wounds had higher scores, supporting construct validity. Excluding scores for wound discharge (purulent and nonpurulent), leaving an eight-item score, provided better measurement statistics. This easily performed wound score appears to be a reliable, valid, and useful tool for predicting clinical outcomes. Further validation studies in different patient populations should refine the items included. C1 [Lipsky, Benjamin A.] Univ Washington, Sch Med, Primary Care Clin, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Polis, Adam B.; Lantz, Keith C.; Norquist, Josephine M.; Abramson, Murray A.] Merck Res Labs, West Point, PA USA. RP Lipsky, BA (reprint author), Univ Washington, Sch Med, Primary Care Clin, VA Puget Sound Hlth Care Syst, S-111 PCC,1660 S Columbian Way, Seattle, WA 98108 USA. EM balipsky@u.washington.edu OI Lipsky, Benjamin A./0000-0001-9886-5114 FU Merck Co. FX We thank Dr. Edward Boyko for reviewing the manuscript and for his suggestions on statistical analyses. The SIDESTEP study was supported by Merck & Co., which also provided assistance with the study design, data acquisition, and statistical and other analyses. NR 26 TC 14 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD SEP-OCT PY 2009 VL 17 IS 5 BP 671 EP 677 DI 10.1111/j.1524-475X.2009.00521.x PG 7 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 493JM UT WOS:000269732700006 PM 19671126 ER PT J AU Pierson, RN Dorling, A Ayares, D Rees, MA Seebach, JD Fishman, JA Hering, BJ Cooper, DKC AF Pierson, Richard N., III Dorling, Anthony Ayares, David Rees, Michael A. Seebach, Joerg D. Fishman, Jay A. Hering, Bernhard J. Cooper, David K. C. TI Current status of xenotransplantation and prospects for clinical application SO XENOTRANSPLANTATION LA English DT Review DE antibody-mediated rejection; coagulation; genetic engineering; pig; pancreatic islets; pig; Pig; xenotransplantation; alpha 1; 3-galactosyltransferase gene-knockout ID PORCINE ENDOTHELIAL-CELLS; HUMAN NK CELLS; DECAY-ACCELERATING FACTOR; ACUTE VASCULAR REJECTION; GENE-KNOCKOUT PIGS; XENOGENEIC TOLERANCE INDUCTION; TO-PRIMATE XENOTRANSPLANTATION; DELAYED XENOGRAFT REJECTION; NATURAL-KILLER-CELL; LONG-TERM SURVIVAL AB Xenotransplantation is one promising approach to bridge the gap between available human cells, tissues, and organs and the needs of patients with diabetes or end-stage organ failure. Based on recent progress using genetically modified source pigs, improving results with conventional and experimental immunosuppression, and expanded understanding of residual physiologic hurdles, xenotransplantation appears likely to be evaluated in clinical trials in the near future for some select applications. This review offers a comprehensive overview of known mechanisms of xenograft injury, a contemporary assessment of preclinical progress and residual barriers, and our opinions regarding where breakthroughs are likely to occur. C1 [Pierson, Richard N., III] Univ Maryland, Div Cardiac Surg, Dept Surg, Baltimore VAMC, Baltimore, MD 21201 USA. [Dorling, Anthony] Univ London Imperial Coll Sci Technol & Med, Dept Immunol, London, England. [Ayares, David] Revivicor Inc, Blacksburg, VA USA. [Ayares, David] Revivicor Inc, Pittsburgh, PA USA. [Rees, Michael A.] Univ Toledo, Dept Urol, Ctr Med, Toledo, OH 43606 USA. [Seebach, Joerg D.] Univ Hosp Geneva, Serv Clin Immunol & Allergol, Dept Internal Med, Geneva, Switzerland. [Seebach, Joerg D.] Fac Med, Geneva, Switzerland. [Fishman, Jay A.] Massachusetts Gen Hosp, Dept Med, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. [Hering, Bernhard J.] Univ Minnesota, Dept Surg, Diabet Inst Immunol & Transplantat, Minneapolis, MN 55455 USA. [Cooper, David K. C.] Univ Pittsburgh, Dept Surg, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. RP Pierson, RN (reprint author), UMMC, N4W94,22 S Greene St, Baltimore, MD 21201 USA. EM rpierson@smail.umaryland.edu OI Dorling, Anthony/0000-0003-3102-2600 FU American Heart Association; VA Merit Program; Office of Naval Research; American Society of Transplant Surgeons; University of Maryland General Clinical Research Center; National Institutes of Health [UO1 AI 066335-01, U01 AI 066719-01, UO1 AI068642, R01 DK066160, U19 AI067151, R21 A1074844]; UK Medical Research Council [G0801965]; Garfield Weston Foundation; Kidney Research UK; ROTRF; Swiss National Science Foundation [3200B0-109921, 32003-114020]; Fondation Wilsdorf; Public Health Services [NIH-NIAID PO1-AI45897]; Juvenile Diabetes Research Foundation [PPG 7-2005-1167]; Diabetes Research; Wellness Foundation; American Diabetes Association FX The authors acknowledge their many colleagues, past and present, who contributed to the work from their own centers that is reviewed in this manuscript, and Christopher Burlak II for his artwork in Figure 5. RNP acknowledges the support of the American Heart Association, VA Merit Program, Office of Naval Research, American Society of Transplant Surgeons, University of Maryland General Clinical Research Center, and National Institutes of Health (NIH: UO1 AI 066335-01 and U01 AI 066719-01). AD was supported by the UK Medical Research Council (G0801965), the Garfield Weston Foundation, Kidney Research UK, the ROTRF, and the NIH (UO1 AI068642). JS was supported by research grants from the Swiss National Science Foundation (3200B0-109921 and 32003-114020), the Fondation Wilsdorf, and by an unconditional contribution of the late Christian Loepfe in support of transplantation research. MR received support from the NIH (R01 DK066160). JAF recognizes support by Public Health Services grant NIH-NIAID PO1-AI45897. BJH received support from the NIH (U19 AI067151), Juvenile Diabetes Research Foundation (PPG 7-2005-1167), Diabetes Research and Wellness Foundation, Eunice L. Dwan Diabetes Research Endowment and Immerge Biotherapeutics. DKCC acknowledges support from the NIH (UO1 AI068642 and R21 A1074844) and the American Diabetes Association. RNP, AD, and DKCC serve on the scientific advisory board of Revivicor, Inc. DA has a significant financial interest in Revivicor, Inc. NR 157 TC 72 Z9 74 U1 1 U2 13 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 263 EP 280 DI 10.1111/j.1399-3089.2009.00534.x PG 18 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500001 PM 19796067 ER PT J AU Koulmanda, M Qipo, A Fan, ZG Singh, G Movahedi, B Duggan, M Kawai, T Strom, TB AF Koulmanda, Maria Qipo, Andi Fan, Zhigang Singh, Gurbakhshish Movahedi, Babak Duggan, Michael Kawai, Tatsuo Strom, Terry B. TI Prevention of non-immunologic loss of transplanted islets in monkeys SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Koulmanda, Maria; Qipo, Andi; Fan, Zhigang; Singh, Gurbakhshish; Movahedi, Babak; Strom, Terry B.] Beth Israel Deaconess Med Ctr, Dept Surg, Inst Transplantat, Boston, MA 02115 USA. [Koulmanda, Maria; Qipo, Andi; Fan, Zhigang; Singh, Gurbakhshish; Movahedi, Babak; Strom, Terry B.] Beth Israel Deaconess Med Ctr, Dept Med, Inst Transplantat, Boston, MA 02115 USA. [Duggan, Michael; Kawai, Tatsuo] Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 299 EP 299 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500038 ER PT J AU Markmann, J Barker, CF Naji, A AF Markmann, J. Barker, C. F. Naji, A. TI Consideration of factors affecting chronic islet allograft dysfunction SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Markmann, J.; Barker, C. F.; Naji, A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 304 EP 304 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500050 ER PT J AU Fishman, JA AF Fishman, J. A. TI Overview: risk assessment in xenotransplantation SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Fishman, J. A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Fishman, J. A.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Fishman, J. A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 305 EP 305 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500053 ER PT J AU Fan, ZG Spencer, J Lu, Y Pitsillides, C Singh, G Kim, P Yun, S Strom, T Lin, C Koulmanda, M AF Fan, Zhigang Spencer, Joel Lu, Yan Pitsillides, Costas Singh, Gurbakhshish Kim, Pilhan Yun, Seok Strom, Terry Lin, Charles Koulmanda, Maria TI In vivo tracking of "color-coded" effector, natural and induced regulatory T cells in allograft response SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Fan, Zhigang; Lu, Yan; Singh, Gurbakhshish; Strom, Terry; Koulmanda, Maria] Harvard Univ, Transplant Inst, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA. [Spencer, Joel; Pitsillides, Costas; Kim, Pilhan; Yun, Seok; Lin, Charles] Massachusetts Gen Hosp, Ctr Syst Biol, Adv Microscopy Program, Wellman Ctr Photomed, Boston, MA 02114 USA. RI Spencer, Joel/A-4590-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 326 EP 327 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500115 ER PT J AU Levesque, VL Bardwell, P Shimizu, I Zhao, GL Moreno, O Buchli, JC Haspot, F Sykes, M AF Levesque, Vanetta L. Bardwell, Philip Shimizu, Ichiro Zhao, Guiling Moreno, Orlando Buchli, Jennifer C. Haspot, Fabienne Sykes, Megan TI Successful induction of mixed chimerism and tolerance with non-myeloablative conditioning in mice presensitized with fully mhc-mismatched skin grafts SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Levesque, Vanetta L.; Bardwell, Philip; Shimizu, Ichiro; Zhao, Guiling; Moreno, Orlando; Buchli, Jennifer C.; Haspot, Fabienne; Sykes, Megan] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 332 EP 332 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500128 ER PT J AU Sachs, D AF Sachs, D. TI Central tolerance: The strongest way SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc ID THYMIC LOBE TRANSPLANTATION; TO-BABOON MODEL; MINIATURE SWINE; COMPOSITE THYMOKIDNEYS; INDUCTION; REJECTION; ANTIBODIES; KIDNEYS; TISSUE C1 [Sachs, D.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 334 EP 335 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500133 ER PT J AU Yamada, K AF Yamada, K. TI Kidney xenotransplantation SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Yamada, K.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 335 EP 336 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500134 ER PT J AU Oriyanhan, W Nishimura, H Okitsu, T Setoyama, K Sahara, H Oku, M Tsubouchi, H Ishikawa, Y Shimizu, A Yamada, K AF Oriyanhan, Wunimenghe Nishimura, Hiroaki Okitsu, Teru Setoyama, Kentaro Sahara, Hisashi Oku, Manei Tsubouchi, Hirohito Ishikawa, Yoshinori Shimizu, Akira Yamada, Kazuhiko TI Life supporting xenogeneic islet transplantation with a regimen including hepatocyte growth factor in a clawn miniature swine-to-cynomologous monkey model SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Oriyanhan, Wunimenghe; Nishimura, Hiroaki; Setoyama, Kentaro; Sahara, Hisashi; Oku, Manei; Tsubouchi, Hirohito; Ishikawa, Yoshinori; Yamada, Kazuhiko] Kagoshima Univ, Frontier Sci Res Ctr, Kagoshima 890, Japan. [Okitsu, Teru] Kyoto Univ, Kyoto 6068501, Japan. [Ishikawa, Yoshinori; Shimizu, Akira; Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 351 EP 352 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500185 ER PT J AU Ishikawa, Y Griesemer, A Weiner, J Moran, S Shimizu, A Sachs, D Yamada, K AF Ishikawa, Yoshinori Griesemer, Adam Weiner, Joshua Moran, Shannon Shimizu, Akira Sachs, David Yamada, Kazuhiko TI High levels of cytotoxic anti-non Gal preformed natural antibody did not induce hyperacute rejection but did cause early graft loss in a GalT-KO pig-to-baboon thymokidney model SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Ishikawa, Yoshinori; Griesemer, Adam; Weiner, Joshua; Moran, Shannon; Shimizu, Akira; Sachs, David; Yamada, Kazuhiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 358 EP 358 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500204 ER PT J AU Weiner, JI Yamada, K Ishikawa, Y Moran, S Etter, J Shimizu, A Smith, RN Sachs, DH AF Weiner, Joshua I. Yamada, Kazuhiko Ishikawa, Yoshinori Moran, Shannon Etter, Justin Shimizu, Akira Smith, R. Neal Sachs, David H. TI Prolonged survival of GalT-KO swine skin on baboons SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Weiner, Joshua I.; Yamada, Kazuhiko; Ishikawa, Yoshinori; Moran, Shannon; Etter, Justin; Shimizu, Akira; Smith, R. Neal; Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 358 EP 358 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500206 ER PT J AU Tena, A Vallabhajousula, P Hawley, R Griesemer, A Yamada, K Sachs, D AF Tena, Aseda Vallabhajousula, Prashanth Hawley, Robert Griesemer, Adam Yamada, Kazuhiko Sachs, David TI Quanti. cation of baboon thymopoiesis in porcine thymokidney xenografts by a signal joining TCR Excision Circle (sjTREC) assay SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E, Charlestown, MA USA. [Vallabhajousula, Prashanth] Johns Hopkins Univ, Baltimore, MD USA. MGH E, Transplant Ctr, MGH, Charlestown, MA USA. [Griesemer, Adam] Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 362 EP 362 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500217 ER PT J AU Yang, Y AF Yang, Y. TI Toll-like receptors/CD47 SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Yang, Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 366 EP 366 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500228 ER PT J AU Levesque, VL Mollov, J Smith, RN Sykes, M AF Levesque, Vanetta L. Mollov, Joshua Smith, Rex N. Sykes, Megan TI Complement fixation and follicular dendritic cell pickup of alpha gal immune complexes are critical for induced anti-gal humoral responses SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Levesque, Vanetta L.; Mollov, Joshua; Sykes, Megan] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Smith, Rex N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 369 EP 369 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500238 ER PT J AU Eguchi, H Habiro, K Yang, YG AF Eguchi, Hiroshi Habiro, Katsuyoshi Yang, Yong-Guang TI Lack of MHC specificity of induced anti-pig antibodies in porcine cell-immunized mice SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Eguchi, Hiroshi; Habiro, Katsuyoshi; Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Eguchi, Hiroshi] Sonoda Womens Univ, Dept Food & Nutr, Amagasaki, Hyogo, Japan. [Habiro, Katsuyoshi] Kansai Med Univ, Inst Biomed Sci, Dept Mol Genet, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 382 EP 382 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500279 ER PT J AU Hector, R Matouskova, M Hejnar, J Crossan, C Fishman, J Takeuchi, Y Scobie, L AF Hector, R. Matouskova, M. Hejnar, J. Crossan, C. Fishman, J. Takeuchi, Y. Scobie, L. TI PERV-C integration, expression and transmission of perv to human cells: is there a link? SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Hector, R.; Crossan, C.; Scobie, L.] Glasgow Caledonian Univ, Glasgow G4 0BA, Lanark, Scotland. [Matouskova, M.; Hejnar, J.] Acad Sci Czech Republic, Inst Mol Genet, CR-14220 Prague 4, Czech Republic. [Fishman, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. [Takeuchi, Y.] UCL, Div Infect & Immun, MRC Ctr Med Mol Virol, London W1T 4JF, England. RI Hejnar, Jiri/G-3544-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 384 EP 384 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500286 ER PT J AU Wang, YT Wang, H Fu, YW Yang, YG AF Wang, Yuantao Wang, Hui Fu, Yaowen Yang, Yong-Guang TI CD47 expression on donor cells is required for tolerance induction by combined DST and CD154 MAB treatment in a mouse model of heart transplantation SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Wang, Yuantao; Wang, Hui; Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Wang, Yuantao; Fu, Yaowen] Jilin Univ, Teaching Hosp 1, Organ Transplantat Ctr, Changchun 130021, Jilin, Peoples R China. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 387 EP 387 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500297 ER PT J AU Lee, KM Zhao, GP Schuetz, C Kim, J Duff, P O'Connor, M Markmann, J Deng, SP AF Lee, Kang Mi Zhao, Gaoping Schuetz, Christian Kim, James Duff, Patrick O'Connor, Matthew Markmann, James Deng, Shaoping TI Anti-CD45RB therapy effectively prevents the rejection of islet allograft by islet-reactive CD4 and CD8 cells in a TCR transgenic model SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Lee, Kang Mi; Zhao, Gaoping; Schuetz, Christian; Kim, James; Duff, Patrick; O'Connor, Matthew; Markmann, James; Deng, Shaoping] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 TC 0 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 403 EP 403 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500351 ER PT J AU Loganathan, G Dawra, RK Papas, KK Pugazhenthi, S Wiseman, A Saluja, AK Sutherland, DER Hering, BJ Appakalai, B AF Loganathan, Gopalakrishnan Dawra, Rajinder K. Papas, Klearchos K. Pugazhenthi, Subbiah Wiseman, Alexander Saluja, Ashok K. Sutherland, David E. R. Hering, Bernhard J. Appakalai, Balamurugan TI Culture of impure human islet fractions in the presence of alpha-1-antitrypsin prevents insulin cleavage and improves islet recovery SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Loganathan, Gopalakrishnan; Papas, Klearchos K.; Sutherland, David E. R.; Hering, Bernhard J.; Appakalai, Balamurugan] Univ Minnesota, Dept Surg, Schulze Diabet Inst, Minneapolis, MN 55455 USA. [Dawra, Rajinder K.; Saluja, Ashok K.] Dept Surg Basic & Transplantat Res, Minneapolis, MN 55455 USA. [Pugazhenthi, Subbiah; Wiseman, Alexander] Univ Colorado, Denver VAMC, Denver, CO 80220 USA. RI Loganathan, Gopalakrishnan/D-8762-2014 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 404 EP 404 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500355 ER PT J AU Brunetti, D Perota, A Lagutina, I Chatelais, M Charreau, B Duchi, R Cozzi, E Lazzari, G Lucchini, F Anegon, I Sachs, DH Galli, C AF Brunetti, Dario Perota, Andrea Lagutina, Irina Chatelais, Mathias Charreau, Beatrice Duchi, Roberto Cozzi, Emanuele Lazzari, Giovanna Lucchini, Franco Anegon, Ignacio Sachs, David H. Galli, Cesare TI Double transgenic Gal(-/-) piglets over-expressing hCD39 SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Brunetti, Dario; Perota, Andrea; Lagutina, Irina; Duchi, Roberto; Lazzari, Giovanna; Galli, Cesare] Ist Sperimentale Italiano Lazzaro Spallanzani, Lab Tecnol Riprod, Cremona, Italy. [Chatelais, Mathias; Charreau, Beatrice; Anegon, Ignacio] Inst Transplantat & Rech Transplantat, INSER, U643, Legnaro, Italy. [Cozzi, Emanuele] Consorzio Ric Trapianto Organo, Legnaro, Italy. [Cozzi, Emanuele] Osped Gen Padova, Direz Sanit, Padua, Italy. [Lucchini, Franco] Univ Cattolica Sacro Cuore, Ctr Ric Biotecnol, Cremona, Italy. [Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Sachs, David H.] Harvard Univ, Sch Med, Boston, MA USA. [Galli, Cesare] Univ Bologna, Dipartimento Clin Vet, Bologna, Italy. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 436 EP 437 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500466 ER PT J AU Levesque, VL Bardwell, P Shimizu, I Zhao, GL Moreno, O Buchli, JC Haspot, F Sykes, M AF Levesque, Vanetta L. Bardwell, Philip Shimizu, Ichiro Zhao, Guiling Moreno, Orlando Buchli, Jennifer C. Haspot, Fabienne Sykes, Megan TI Successful induction of mixed chimerism and tolerance with non-myeloablative conditioning in mice presensitized with fully MHC-mismatched skin grafts SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Levesque, Vanetta L.; Bardwell, Philip; Shimizu, Ichiro; Zhao, Guiling; Moreno, Orlando; Buchli, Jennifer C.; Haspot, Fabienne; Sykes, Megan] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 441 EP 441 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500479 ER PT J AU Fihn, SD Vaughan-Sarrazin, M Lowy, E Popescu, I Maynard, C Rosenthal, GE Sales, AE Rumsfeld, J Pineros, S McDonell, MB Helfrich, CD Rusch, R Jesse, R Almenoff, P Fleming, B Kussman, M AF Fihn, Stephan D. Vaughan-Sarrazin, Mary Lowy, Elliott Popescu, Ioana Maynard, Charles Rosenthal, Gary E. Sales, Anne E. Rumsfeld, John Pineros, Sandy McDonell, Mary B. Helfrich, Christian D. Rusch, Roxane Jesse, Robert Almenoff, Peter Fleming, Barbara Kussman, Michael TI Declining mortality following acute myocardial infarction in the Department of Veterans Affairs Health Care System SO BMC CARDIOVASCULAR DISORDERS LA English DT Article ID MEDICARE; QUALITY; US; TRANSFORMATION; ANGIOPLASTY; OUTCOMES; THERAPY; DISEASE AB Background: Mortality from acute myocardial infarction (AMI) is declining worldwide. We sought to determine if mortality in the Veterans Health Administration (VHA) has also been declining. Methods: We calculated 30-day mortality rates between 2004 and 2006 using data from the VHA External Peer Review Program (EPRP), which entails detailed abstraction of records of all patients with AMI. To compare trends within VHA with other systems of care, we estimated relative mortality rates between 2000 and 2005 for all males 65 years and older with a primary diagnosis of AMI using administrative data from the VHA Patient Treatment File and the Medicare Provider Analysis and Review (MedPAR) files. Results: Using EPRP data on 11,609 patients, we observed a statistically significant decline in adjusted 30-day mortality following AMI in VHA from 16.3% in 2004 to 13.9% in 2006, a relative decrease of 15% and a decrease in the odds of dying of 10% per year (p = .011). Similar declines were found for in-hospital and 90-day mortality. Based on administrative data on 27,494 VHA patients age 65 years and older and 789,400 Medicare patients, 30-day mortality following AMI declined from 16.0% during 2000-2001 to 15.7% during 2004-June 2005 in VHA and from 16.7% to 15.5% in private sector hospitals. After adjusting for patient characteristics and hospital effects, the overall relative odds of death were similar for VHA and Medicare (odds ratio 1.02, 95% C.I. 0.96-1.08). Conclusion: Mortality following AMI within VHA has declined significantly since 2003 at a rate that parallels that in Medicare-funded hospitals. C1 [Fihn, Stephan D.; Lowy, Elliott; Maynard, Charles; Pineros, Sandy; Helfrich, Christian D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Fihn, Stephan D.] Univ Washington, Dept Med, Seattle, WA USA. [Fihn, Stephan D.; Helfrich, Christian D.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Vaughan-Sarrazin, Mary; Popescu, Ioana; Rosenthal, Gary E.; McDonell, Mary B.] VA Med Ctr, Iowa City, IA USA. [Vaughan-Sarrazin, Mary; Popescu, Ioana; Rosenthal, Gary E.; McDonell, Mary B.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA. [Sales, Anne E.] Univ Alberta, Edmonton, AB, Canada. [Rumsfeld, John] VA Med Ctr, Denver, CO USA. [Rumsfeld, John] Univ Colorado, Dept Med, Denver, CO USA. [Rusch, Roxane; Jesse, Robert; Almenoff, Peter; Fleming, Barbara; Kussman, Michael] Dept Vet Affairs, Washington, DC USA. RP Fihn, SD (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM Stephan.Fihn@va.gov; Mary.Vaughan@va.gov; Elliott.Lowy@va.gov; Ioanna.Popescu@va.gov; Charles.Maynard@va.gov; Gary-Rosenthal@uiowa.edu; Anne.Sales@ualberta.ca; John.Rumsfeld@va.gov; vanbrit@hotmail.com; Mary.McDonell@va.gov; Christian.Helfrich@va.gov; Roxane.Rusch@va.gov; Jesse.Robert_r@richmond.va.gov; Peter.Almenoff@va.gov; Barbflem@comcast.net; Michael.Kussman@va.gov RI Sales, Anne/D-9678-2012; Maynard, Charles/N-3906-2015; Helfrich, Christian/D-2382-2016; OI Maynard, Charles/0000-0002-1644-7814; Helfrich, Christian/0000-0002-9827-4768; Vaughan Sarrazin, Mary/0000-0001-8717-1061; Sales, Anne/0000-0001-9360-3334 FU Department of Veterans Affairs [MRC 03-334] FX This work was supported by the Department of Veterans Affairs, grant MRC 03-334. NR 27 TC 15 Z9 15 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2261 J9 BMC CARDIOVASC DISOR JI BMC Cardiovasc. Disord. PD AUG 31 PY 2009 VL 9 AR 44 DI 10.1186/1471-2261-9-44 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 500KA UT WOS:000270296600001 PM 19719849 ER PT J AU Petersen, T Andreotti, CF Chelminski, I Young, D Zimmerman, M AF Petersen, Timothy Andreotti, Charissa F. Chelminski, Iwona Young, Diane Zimmerman, Mark TI Do comorbid anxiety disorders impact treatment planning for outpatients with major depressive disorder? SO PSYCHIATRY RESEARCH LA English DT Article DE Major depressive disorder; Treatment planning; Comorbid anxiety disorders ID STAR-ASTERISK-D; PSYCHIATRIC OUTPATIENTS; MULTICENTER; FEATURES AB Research indicates that depressed patients with comorbid anxiety disorders have a poorer long-term course of illness, are less responsive to treatment, and may experience greater deficits in psychosocial functioning, when compared with depressed patients without comorbid anxiety disorders. The objective of this study was to examine, through use of a large. well-characterized clinical database, how clinicians may modify treatment recommendations in depressed outpatients when anxiety disorders are present. A group of 346 case records, derived from the Methods to Improve Diagnostic Assessment and Services (MIDAS) project at Rhode Island Hospital, were examined to determine what treatment recommendations were made immediately after diagnosis. Psychopharmacological and psychotherapeutic treatments were classified to capture differences in recommendations between groups. Demographic and clinical characteristics were compared for patients with (n = 248) and without (n = 98) comorbid anxiety disorders. Utilizing logistic regression models, we found patients with anxiety disorders had a greater number of psychopharmacological therapies included as part of their initial treatment plan, but no differences were found in initial psychotherapeutic interventions. Our results indicate that practitioners are making unique recommendations based on comorbid anxiety diagnoses, but outcome studies are now needed to determine the most effective treatment methods for this patient population. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Petersen, Timothy; Andreotti, Charissa F.] Massachusetts Gen Hosp, Dept Psychiat, Div Postgrad Educ, Boston, MA 02114 USA. [Chelminski, Iwona; Young, Diane; Zimmerman, Mark] Brown Univ, Sch Med, Rhode Isl Hosp, Dept Psychiat & Human Behav, Providence, RI 02905 USA. RP Petersen, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Div Postgrad Educ, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM tpetersen@partners.org NR 24 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD AUG 30 PY 2009 VL 169 IS 1 BP 7 EP 11 DI 10.1016/j.psychres.2008.10.036 PG 5 WC Psychiatry SC Psychiatry GA 489QW UT WOS:000269437600002 PM 19596155 ER PT J AU Kaufman, MJ Prescot, AP Ongur, D Evins, AE Barros, TL Medeiros, CL Covell, J Wang, LQ Fava, M Renshaw, PF AF Kaufman, Marc J. Prescot, Andrew P. Ongur, Dost Evins, A. Eden Barros, Tanya L. Medeiros, Carissa L. Covell, Julie Wang, Liqun Fava, Maurizio Renshaw, Perry F. TI Oral glycine administration increases brain glycine/creatine ratios in men: A proton magnetic resonance spectroscopy study SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 14, 2007 CL Boca Raton, FL SP Amer Coll Neuropsychopharmacol DE Schizophrenia; Antipsychotic; Glutamate receptors; Substance abuse ID HIGH-DOSE GLYCINE; TREATMENT-RESISTANT SCHIZOPHRENIA; ESSENTIAL AMINO-ACIDS; D-SERINE; IN-VIVO; NEGATIVE SYMPTOMS; NMDA RECEPTOR; D-CYCLOSERINE; GLUTAMATERGIC TRANSMISSION; SELECTIVE INHIBITOR AB Oral high-dose glycine administration has been used as an adjuvant treatment for schizophrenia to enhance glutamate neurotransmission and mitigate glutamate system hypofunction thought to contribute to the disorder. Prior studies in schizophrenia subjects documented clinical improvements after 2 weeks of oral glycine administration, suggesting that brain glycine levels are sufficiently elevated to evoke a clinical response within that time frame. However, no human study has reported on brain glycine changes induced by its administration. We utilized a noninvasive proton magnetic resonance spectroscopy ((1)H-MRS) technique termed echo time-averaged (TEAV) (1)H-MRS, which permits noninvasive quantification of brain glycine in vivo, to determine whether 2 weeks of oral glycine administration (peak dose of 0.8 g/kg/day) increased brain glycine/creatine (Gly/Cr) ratios in 11 healthy adult men. In scans obtained 17 h after the last glycine dose, brain (Gly/Cr) ratios were significantly increased. The data indicate that it is possible to measure brain glycine changes with proton spectroscopy. Developing a more comprehensive understanding of human brain glycine dynamics may lead to optimized use of glycine site agonists and glycine transporter inhibitors to treat schizophrenia, and possibly to treat other disorders associated with glutamate system dysfunction. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Kaufman, Marc J.; Prescot, Andrew P.; Ongur, Dost; Barros, Tanya L.; Medeiros, Carissa L.; Covell, Julie; Renshaw, Perry F.] Harvard Univ, Brain Imaging Ctr, Sch Med, McLean Hosp, Belmont, MA 02478 USA. [Evins, A. Eden; Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, Liqun] GlaxoSmithKline Inc, Translat Med & Genet, Greenford, Middx, England. [Renshaw, Perry F.] Univ Utah, Inst Brain, Salt Lake City, UT USA. RP Kaufman, MJ (reprint author), Harvard Univ, Brain Imaging Ctr, Sch Med, McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM kaufman@mclean.harvard.edu FU NCRR NIH HHS [RR013938, S10 RR013938, S10 RR013938-01]; NIDA NIH HHS [DA017324, DA022276, R01 DA014674, R01 DA022276-02, U01 DA019378-03, DA014674, DA019378, K02 DA017324, K02 DA017324-05, R01 DA014674-04, R01 DA022276, U01 DA019378] NR 70 TC 11 Z9 11 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD AUG 30 PY 2009 VL 173 IS 2 BP 143 EP 149 DI 10.1016/j.pscychresns.2009.03.004 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 485HX UT WOS:000269113000010 PM 19556112 ER PT J AU Peluso, MAM Glahn, DC Matsuo, K Monkul, ES Najt, P Zamarripa, F Li, JQ Lancaster, JL Fox, PT Gao, JH Soares, JC AF Peluso, Marco A. M. Glahn, David C. Matsuo, Koji Monkul, E. Serap Najt, Pablo Zamarripa, Frank Li, Jinqi Lancaster, Jack L. Fox, Peter T. Gao, Jia-Hong Soares, Jair C. TI Amygdala hyperactivation in untreated depressed individuals SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Depressive disorder; Amygdala; Facial expression; Functional MRI ID FACIAL EXPRESSIONS; ANTIDEPRESSANT TREATMENT; NEURAL RESPONSE; MOOD DISORDERS; FACES; PERCEPTION; FMRI AB The amygdala participates in the detection and control of affective states, and has been proposed to be a site of dysfunction in affective disorders. To assess amygdala processing in individuals with unipolar depression, we applied a functional MRI (fMRI) paradigm previously shown to be sensitive to amygdala function. Fourteen individuals with untreated DSM-IV major depression and 15 healthy subjects were studied using fMRI with a standardized emotion face recognition task. Voxel-level data sets were subjected to a multiple-regression analysis, and functionally defined regions of interest (ROI), including bilateral amygdala, were analyzed with MANOVA. Pearson correlation coefficients between amygdala activation and HAM-D score also were performed. While both depressed and healthy groups showed increased amygdala activity when viewing emotive faces compared to geometric shapes, patients with unipolar depression showed relatively more activity than healthy subjects, particularly on the left. Positive Pearson correlations between amygdala activation and HAM-D score were found for both left and right ROIs in the patient group. This study provides in vivo imaging evidence to support the hypothesis of abnormal amygdala functioning in depressed individuals. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Peluso, Marco A. M.] Univ Sao Paulo, Sect Psychiat Epidemiol, Dept Psychiat, CEAPESQ, BR-05403010 Sao Paulo, Brazil. [Peluso, Marco A. M.; Glahn, David C.; Matsuo, Koji; Monkul, E. Serap; Najt, Pablo; Soares, Jair C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Peluso, Marco A. M.; Matsuo, Koji; Monkul, E. Serap; Najt, Pablo; Soares, Jair C.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Glahn, David C.; Zamarripa, Frank; Li, Jinqi; Lancaster, Jack L.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, San Antonio, TX 78229 USA. [Monkul, E. Serap] Dokuz Eylul Univ, Dept Psychiat, Izmir, Turkey. [Gao, Jia-Hong; Soares, Jair C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. RP Peluso, MAM (reprint author), Univ Sao Paulo, Sect Psychiat Epidemiol, Dept Psychiat, CEAPESQ, Av Dr Ovidio Pires de Campos 785,3O Andar,Sala 17, BR-05403010 Sao Paulo, Brazil. EM mampeluso@hotmail.com RI Lancaster, Jack/F-2994-2010; Fox, Peter/B-4725-2010; Li, Jinqi/F-7778-2010; Frank, David/E-8213-2012 OI Fox, Peter/0000-0002-0465-2028; FU UTHSCSA GCRC [M01-RR-01346]; Dana Founda-Administration (VA Merit Review); CNPq ("Conselho Nacional de Desenvolvimento Cientifico e Tecnologico", Brazil [200006/04-5]; [MH 01736]; [MH 068662]; [RR020571] FX This research was partly supported by grants MH 01736, MH 068662, RR020571, UTHSCSA GCRC (M01-RR-01346), Dana Founda-Administration (VA Merit Review), and CNPq ("Conselho Nacional de Desenvolvimento Cientifico e Tecnologico", Brazil - grant# 200006/04-5). NR 23 TC 64 Z9 64 U1 0 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD AUG 30 PY 2009 VL 173 IS 2 BP 158 EP 161 DI 10.1016/j.pscychresns.2009.03.006 PG 4 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 485HX UT WOS:000269113000013 PM 19545982 ER PT J AU Chen, HY Gao, SS AF Chen, Hua Yun Gao, Shasha TI Estimation of average treatment effect with incompletely observed longitudinal data: Application to a smoking cessation study SO STATISTICS IN MEDICINE LA English DT Article DE causal effect; potential outcomes; robust estimator; surrogate outcome ID LINEAR MIXED MODELS; MARGINALIZED TRANSITION MODELS; IGNORABLE MISSING DATA; CAUSAL INFERENCE; BINARY DATA; DROP-OUT; SEMIPARAMETRIC REGRESSION; NONRESPONSE MODELS; LOCAL SENSITIVITY; REPEATED OUTCOMES AB We stud the problem of estimation and inference oil the average treatment effect in a smoking, cessation trial where an outcome and some auxiliary information were measured longitudinally. and both were subject to missing Values. Dynamic generalized linear mixed effects models linking the outcome, the auxiliary information, and the covariates are proposed. The maximum likelihood approach is applied to the estimation and inference of the model Parameters. The average treatment effect is estimated by the G-computation approach. and the sensitivity of the treatment effect estimate to the nonignorable missing data mechanisms is investigated through the local sensitivity analysis approach. The Proposed approach call handle missing data that form arbitrary missing patterns over little. We applied the proposed method to the analysis of the smoking cessation trial. Copyright (C) 2009 John Wiley & Sons. Ltd. C1 [Chen, Hua Yun] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL 60612 USA. [Gao, Shasha] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. RP Chen, HY (reprint author), Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, 1603 W Taylor St, Chicago, IL 60612 USA. EM hychen@uic.edu FU NIH/NCI [R01 CA106355] FX Contract/grant sponsor: NIH/NCI contract/grant number: R01 CA106355 NR 38 TC 3 Z9 3 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 30 PY 2009 VL 28 IS 19 BP 2451 EP 2472 DI 10.1002/sim.3617 PG 22 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 475PY UT WOS:000268373500003 PM 19462416 ER PT J AU Ye, J Lazar, NA Li, YH AF Ye, Jun Lazar, Nicole A. Li, Yehua TI Geostatistical analysis in clustering fMRI time series SO STATISTICS IN MEDICINE LA English DT Article DE autocorrelation; masking; marginal effect; silhouette values; structural classification ID HEMODYNAMIC-RESPONSE; NEUROIMAGING DATA; FUNCTIONAL MRI; CLASSIFICATION; VALIDATION; SACCADES; MODELS AB Clustering of functional magnetic resonance imaging (fMRI) time series-either directly or through characteristic features such as the cross-correlation with the experimental protocol signal-has been extensively used for the identification of active regions in the brain. Both approaches have drawbacks; clustering of the time series themselves may identify voxels with similar temporal behavior that is unrelated to the stimulus, whereas cross-correlation requires knowledge of the stimulus presentation protocol. In this paper we propose the use of autocorrelation structure instead-an idea borrowed from geostatistics; this approach does not suffer from the deficits associated with previous clustering methods. We first formalize the traditional classification methods as three steps: feature extraction, choice of classification metric and choice of classification algorithm. The use of different characteristics to effect the clustering (cross-correlation, autocorrelation, and so forth) relates to the first of these three steps. We then demonstrate the efficacy of autocorrelation clustering on a simple visual task and on resting data. A byproduct of our analysis is the finding that masking prior to clustering, as is commonly done, may degrade the quality of the discovered clusters, and we offer an explanation for this phenomenon. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Ye, Jun] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lazar, Nicole A.; Li, Yehua] Univ Georgia, Dept Stat, Athens, GA 30602 USA. RP Ye, J (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM athensye@yahoo.com FU NSF [DMS-0706192] FX Contract/grant sponsor: NSF, contract/grant number: DMS-0706192 NR 42 TC 8 Z9 8 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 30 PY 2009 VL 28 IS 19 BP 2490 EP 2508 DI 10.1002/sim.3626 PG 19 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 475PY UT WOS:000268373500005 PM 19521974 ER PT J AU Chen, YX Gelfond, JAL McManus, LM Shireman, PK AF Chen, Yongxin Gelfond, Jonathan A. L. McManus, Linda M. Shireman, Paula K. TI Reproducibility of quantitative RT-PCR array in miRNA expression profiling and comparison with microarray analysis SO BMC GENOMICS LA English DT Article ID MICRORNA EXPRESSION; GENE-EXPRESSION; OLIGONUCLEOTIDE MICROARRAYS; MAMMALIAN MICRORNAS; MESSENGER-RNA; IDENTIFICATION; CELLS; DIFFERENTIATION; QUANTIFICATION; NEUROBLASTOMA AB Background: MicroRNAs (miRNAs) have critical functions in various biological processes. MiRNA profiling is an important tool for the identification of differentially expressed miRNAs in normal cellular and disease processes. A technical challenge remains for high-throughput miRNA expression analysis as the number of miRNAs continues to increase with in silico prediction and experimental verification. Our study critically evaluated the performance of a novel miRNA expression profiling approach, quantitative RT-PCR array (qPCR-array), compared to miRNA detection with oligonucleotide microchip (microarray). Results: High reproducibility with qPCR-array was demonstrated by comparing replicate results from the same RNA sample. Pre-amplification of the miRNA cDNA improved sensitivity of the qPCR-array and increased the number of detectable miRNAs. Furthermore, the relative expression levels of miRNAs were maintained after pre-amplification. When the performance of qPCR-array and microarrays were compared using different aliquots of the same RNA, a low correlation between the two methods (r = -0.443) indicated considerable variability between the two assay platforms. Higher variation between replicates was observed in miRNAs with low expression in both assays. Finally, a higher false positive rate of differential miRNA expression was observed using the microarray compared to the qPCR-array. Conclusion: Our studies demonstrated high reproducibility of TaqMan qPCR-array. Comparison between different reverse transcription reactions and qPCR-arrays performed on different days indicated that reverse transcription reactions did not introduce significant variation in the results. The use of cDNA pre-amplification increased the sensitivity of miRNA detection. Although there was variability associated with pre-amplification in low abundance miRNAs, the latter did not involve any systemic bias in the estimation of miRNA expression. Comparison between microarray and qPCR-array indicated superior sensitivity and specificity of qPCR-array. C1 [Chen, Yongxin; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Chen, Yongxin; Shireman, Paula K.] S Texas Vet Hlth Care Syst, Dept Surg, San Antonio, TX 78229 USA. [Gelfond, Jonathan A. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. RP Chen, YX (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. EM cheny4@uthscsa.edu; gelfondjal@uthscsa.edu; mcmanus@uthscsa.edu; shireman@uthscsa.edu FU Veterans Administration Merit Review; National Institutes of Health [R01HL074236, T32HL07446]; National Center for Research Resources [KL2 RR025766] FX These studies were supported, in part, by a Veterans Administration Merit Review grant and the National Institutes of Health (R01HL074236 and T32HL07446) from the National Heart, Lung, and Blood Institute and CTSA Award (KL2 RR025766) 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 Institutes of Health. The authors have no relationships that pose a conflict of interest for these studies. NR 41 TC 136 Z9 140 U1 0 U2 25 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD AUG 28 PY 2009 VL 10 AR 407 DI 10.1186/1471-2164-10-407 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 501PR UT WOS:000270394300002 PM 19715577 ER PT J AU Liu, E McKeown, NM Newby, PK Meigs, JB Vasan, RS Quatromoni, PA D'Agostin, RB Jacques, PF AF Liu, Enju McKeown, Nicola M. Newby, P. K. Meigs, James B. Vasan, Ramachandran S. Quatromoni, Paula A. D'Agostin, Ralph B. Jacques, Paul F. TI Cross-sectional association of dietary patterns with insulin-resistant phenotypes among adults without diabetes in the Framingham Offspring Study SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE Dietary patterns; Cluster analysis; Insulin-resistant phenotypes; Framingham Offspring Study ID CORONARY-HEART-DISEASE; FOOD-FREQUENCY QUESTIONNAIRE; DENSITY-LIPOPROTEIN CHOLESTEROL; SUGAR-SWEETENED DRINKS; METABOLIC RISK-FACTORS; GLYCEMIC INDEX; CLUSTER-ANALYSIS; CARDIOVASCULAR-DISEASE; AGED ADULTS; WOMEN AB Cluster analysis is a valuable tool for exploring the health consequences of consuming different dietary patterns. We used this approach to examine the cross-sectional relationship between dietary patterns and insulin-resistant phenotypes, including waist circumference, BMI. fasting insulin, 2h post-challenge insulin, insulin sensitivity index (ISI(0.120)), HDL-cholesterol, TAG and blood pressure, using data from the fifth examination cycle of the Framingham Offspring Study. Among 2875 participants without diabetes, we identified four dietary patterns based on the predominant sources of energy: 'Fruits, Reduced Fat Dairy and Whole Grains', 'Refined Grains and Sweets', 'Beer' and 'Soda'. After adjusting for multiple comparisons and potential confounders, compared with the 'Fruits, Reduced Fat Dairy and Whole Grains' pattern, the 'Refined Grains and Sweets' pattern had significantly higher mean waist circumference (92.4 v. 90.5cm; P=0.008) and BMI (27.3 v. 26.6 kg/m(2); P=0.02); the 'Soda' pattern had significantly higher mean fasting insulin concentration (31.3 v. 28.0 mu U/ml; P <= 0.001); the 'Beer' pattern had significantly higher mean HDL-cholesterol concentration (1-46 v. 1.31 mmol/l; P<0.001). No associations were observed between dietary patterns and ISI(0.120), TAG, and systolic or diastolic blood pressure. Our findings suggest that consumption of a diet rich in fruits, vegetables, whole grains and reduced-fat dairy protects against insulin-resistant phenotypes and displacing these healthy choices with refined grains, high-fat dairy, sweet baked foods, candy and sugar-sweetened soda may promote insulin-resistant phenotypes. C1 [Liu, Enju; McKeown, Nicola M.; Jacques, Paul F.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA. [Liu, Enju; McKeown, Nicola M.; Jacques, Paul F.] Tufts Univ, Gerald J & Dorothy R Friedman Sch Nutr Sci & Poli, Boston, MA 02111 USA. [Newby, P. K.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Newby, P. K.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02118 USA. [Quatromoni, Paula A.] Boston Univ, Dept Hlth Sci, Sargent Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. [D'Agostin, Ralph B.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP McKeown, NM (reprint author), Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA. EM nicola.mckeown@tufts.edu RI liu, enju/B-2136-2010; liu, enju/F-4062-2010; OI Ramachandran, Vasan/0000-0001-7357-5970 FU US Department of Agriculture [58-1950-7-707]; National Institutes of Health [N01-HC-25195]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [K24 DK080140, 2K24 HL04334]; General Mills Bell Institute of Health and Nutrition FX The supplementary material for this article can be found at http://www.joumals.cambridge.org/bjn NR 59 TC 31 Z9 31 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD AUG 28 PY 2009 VL 102 IS 4 BP 576 EP 583 DI 10.1017/S0007114509220836 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 485RR UT WOS:000269141900016 PM 19216828 ER PT J AU Jin, Y An, XJ Ye, ZL Cully, B Wu, JP Li, J AF Jin, Yi An, Xiaojin Ye, Zelian Cully, Brittany Wu, Jiaping Li, Jian TI RGS5, a Hypoxia-inducible Apoptotic Stimulator in Endothelial Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR; GENE-EXPRESSION; MEDIATED APOPTOSIS; ANGIOTENSIN-II; FACTOR 1-ALPHA; DEATH; PROLIFERATION; ANGIOGENESIS AB Endothelial cells rapidly respond to changes in oxygen homeostasis by regulating gene expression. Regulator of G protein signaling 5 (RGS5) is a negative regulator of G protein-mediated signaling that is strongly expressed in vessels during angiogenesis; however, the role of RGS5 in hypoxia has not been fully understood. Under hypoxic conditions, we found that the expression of RGS5, but not other RGS, was induced in human umbilical vein endothelial cells (HUVEC). RGS5 mRNA was increased when HUVEC were incubated with chemicals that stabilized hypoxia-inducible factor-1 alpha (HIF-1 alpha), whereas hypoxia-stimulated RGS5 promoter activity was absent in HIF-1 beta(-/-) cells. Vascular endothelial growth factor (VEGF), which is regulated by HIF-1, did not appear to be involved in hypoxia-induced RGS5 expression; however, VEGF-mediated activation of p38 but not ERK1/2 was increased by RGS5. Overexpression of RGS5 in HUVEC exhibited a reduced growth rate without affecting the cell proliferation. Annexin V assay revealed that RGS5 induced apoptosis with significantly increased activation of caspase-3 and the Bax/Bcl-2 ratio. Small interfering RNA-specific for RGS5, caspase-3 inhibitor, and p38 inhibitor resulted in an attenuation of RGS5-stimulated apoptosis. Matrigel assay proved that RGS5 significantly impaired the angiogenic effect of VEGF and stimulated apoptosis in vivo. We concluded that RGS5 is a novel HIF-1-dependent, hypoxia-induced gene that is involved in the induction of endothelial apoptosis. Moreover, RGS5 antagonizes the angiogenic effect of VEGF by increasing the activation of p38 signaling, suggesting that RGS5 could be an important target for apoptotic therapy. C1 [Li, Jian] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med,Ctr Life Sci, Boston, MA 02215 USA. [Jin, Yi; An, Xiaojin; Ye, Zelian; Li, Jian] Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. RP Li, J (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med,Ctr Life Sci, CLS 909,3 Blackfan Circle, Boston, MA 02215 USA. EM jli@bidmc.harvard.edu FU National Institutes of Health [HLR01082837]; American Heart Association [0265494T]; China Scholarship Council FX This work was supported in part by National Institutes of Health Grant HLR01082837 (to J.L.). This work was also supported by American Heart Association Grant-in-aid 0265494T (to J.L.) and the China Scholarship Council (to J.Y. and X. A.). NR 43 TC 26 Z9 30 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 2009 VL 284 IS 35 BP 23436 EP 23443 DI 10.1074/jbc.M109.032664 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 486EZ UT WOS:000269180000028 PM 19564336 ER PT J AU Fischbach, MA Walsh, CT AF Fischbach, Michael A. Walsh, Christopher T. TI Antibiotics for Emerging Pathogens SO SCIENCE LA English DT Review ID RESISTANT STAPHYLOCOCCUS-AUREUS; NATURAL-PRODUCTS; ANTIBACTERIAL DISCOVERY; DRUG DISCOVERY; MYCOBACTERIUM-TUBERCULOSIS; INHIBITOR; BIOSYNTHESIS; INFECTIONS; TARGET; POTENT AB Antibiotic-resistant strains of pathogenic bacteria are increasingly prevalent in hospitals and the community. New antibiotics are needed to combat these bacterial pathogens, but progress in developing them has been slow. Historically, most antibiotics have come from a small set of molecular scaffolds whose functional lifetimes have been extended by generations of synthetic tailoring. The emergence of multidrug resistance among the latest generation of pathogens suggests that the discovery of new scaffolds should be a priority. Promising approaches to scaffold discovery are emerging; they include mining underexplored microbial niches for natural products, designing screens that avoid rediscovering old scaffolds, and repurposing libraries of synthetic molecules for use as antibiotics. C1 [Fischbach, Michael A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Fischbach, Michael A.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Walsh, Christopher T.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Fischbach, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM fischbach@fischbachgroup.org; christopher_walsh@hms.harvard.edu FU Department of Molecular Biology; Center for Computational and Integrative Biology; Massachusetts General Hospital; NIH [GM20011, GM49338] FX Research in the authors laboratories is supported by the Department of Molecular Biology and the Center for Computational and Integrative Biology at Massachusetts General Hospital (M.A.F.) and by NIH grants GM20011 and GM49338 (C.T.W.). C.T.W. is a member of the board of directors of Achaogen (South San Francisco, CA). NR 51 TC 687 Z9 708 U1 33 U2 309 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD AUG 28 PY 2009 VL 325 IS 5944 BP 1089 EP 1093 DI 10.1126/science.1176667 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 488WZ UT WOS:000269382300030 PM 19713519 ER PT J AU Kumar, S Giralt, S Stadtmauer, EA Harousseau, JL Palumbo, A Bensinger, W Comenzo, RL Lentzsch, S Munshi, N Niesvizky, R Miguel, JS Ludwig, H Bergsagel, L Blade, J Lonial, S Anderson, KC Tosi, P Sonneveld, P Sezer, O Vesole, D Cavo, M Einsele, H Richardson, PG Durie, BGM Rajkumar, SV AF Kumar, Shaji Giralt, Sergio Stadtmauer, Edward A. Harousseau, Jean L. Palumbo, Antonio Bensinger, William Comenzo, Raymond L. Lentzsch, Suzanne Munshi, Nikhil Niesvizky, Ruben Miguel, Jesus San Ludwig, Heinz Bergsagel, Leif Blade, Joan Lonial, Sagar Anderson, Kenneth C. Tosi, Patrizia Sonneveld, Pieter Sezer, Orhan Vesole, David Cavo, Michele Einsele, Hermann Richardson, Paul G. Durie, Brian G. M. Rajkumar, S. Vincent CA Int Myeloma Working Grp IMWG TI Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide-, lenalidomide-, or bortezomib-containing regimens SO BLOOD LA English DT Article ID DIAGNOSED MULTIPLE-MYELOMA; HIGH-DOSE THERAPY; RANDOMIZED CLINICAL-TRIAL; COLONY-STIMULATING FACTOR; PLUS DEXAMETHASONE; AUTOLOGOUS TRANSPLANTATION; COMBINATION THERAPY; STANDARD CHEMOTHERAPY; IMPROVES SURVIVAL; CXCR4 ANTAGONIST AB The past decade has witnessed a paradigm shift in the initial treatment of multiple myeloma with the introduction of novel agents such as thalidomide, lenalidomide, and bortezomib, leading to improved outcomes. High-dose therapy and autologous stem cell transplantation remains an important therapeutic option for patients with multiple myeloma eligible for the procedure. Before the advent of the novel agents, patients underwent stem cell collection prior to significant alkylating agent exposure, given its potential deleterious effect on stem cell collection. With increasing use of the novel agents in the upfront setting, several reports have emerged raising concerns about their impact on the ability to collect stem cells. An expert panel of the International Myeloma Working Group (IMWG) was convened to examine the implications of these therapies on stem collection in patients with myeloma and to develop recommendations for addressing these issues. Here we summarize the currently available data and present our perspective on the problem and potential options to overcome this problem. Specifically, we recommend early mobilization of stem cells, preferably within the first 4 cycles of initial therapy, in patients treated with novel agents and encourage participation in clinical trials evaluating novel approaches to stem cell mobilization. (Blood. 2009;114:1729-1735) C1 [Kumar, Shaji; Bergsagel, Leif; Rajkumar, S. Vincent] Mayo Clin, Div Hematol, Rochester, MN 55906 USA. [Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Bone Marrow & Stem Cell Transplant Program, Philadelphia, PA 19104 USA. [Harousseau, Jean L.] Inst Biol, Dept Hematol, Nantes, France. [Palumbo, Antonio] Univ Turin, Azienda Osped S Giovanni Battista, Osped Molinette Torino, Div Ematol, Turin, Italy. [Bensinger, William] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Comenzo, Raymond L.] Mem Sloan Kettering Canc Ctr, Dept Clin Labs, New York, NY 10021 USA. [Lentzsch, Suzanne] Univ Pittsburgh, Div Hematol Oncol, UMPC Canc Pavil, Pittsburgh, PA 15260 USA. [Munshi, Nikhil; Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. [Niesvizky, Ruben] Weill Cornell Med Coll, New York, NY USA. [Miguel, Jesus San] Hosp Univ Salamanca, USAL, IBMCC, CIC,CSIC,Serv Hepatol,Dept Hematol, Salamanca, Spain. [Ludwig, Heinz] Wilhelminenspital Stadt Wien, Ctr Oncol & Hematol, Dept Med 1, Vienna, Austria. [Blade, Joan] Hosp Clin Barcelona, IDIBAPS, Dept Hematol, Barcelona, Spain. [Lonial, Sagar] Emory Univ, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Tosi, Patrizia] Univ Bologna, Inst Hematol & Med Oncol, Bologna, Italy. [Sonneveld, Pieter] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Sezer, Orhan] Univ Berlin, Dept Hematol Oncol, Berlin, Germany. [Vesole, David] Loyola Univ, Div Hematol Oncol, Chicago, IL 60611 USA. [Cavo, Michele] Inst Hematol & Med Oncol Seragnoli, Bologna, Italy. [Einsele, Hermann] Univ Wurzburg, Dept Internal Med, Wurzburg, Germany. [Durie, Brian G. M.] Aptium Oncol Inc, Cedars Sinai Outpatient Canc Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA USA. RP Kumar, S (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55906 USA. EM shaji@mayo.edu RI 2009, Secribsal/A-1266-2012; Bergsagel, Peter/A-7842-2011; Kumar, Shaji/A-9853-2008; OI Bergsagel, Peter/0000-0003-1523-7388; Kumar, Shaji/0000-0001-5392-9284; CAVO, MICHELE/0000-0003-4514-3227; Rajkumar, S. Vincent/0000-0002-5862-1833; SAN MIGUEL, JESUS/0000-0002-9183-4857 NR 64 TC 110 Z9 113 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD AUG 27 PY 2009 VL 114 IS 9 BP 1729 EP 1735 DI 10.1182/blood-2009-04-205013 PG 7 WC Hematology SC Hematology GA 488WI UT WOS:000269380600007 PM 19561323 ER PT J AU Borrello, IM Levitsky, HI Stock, W Sher, D Qin, L DeAngelo, DJ Alyea, EP Stone, RM Damon, LE Linker, CA Maslyar, DJ Hege, KM AF Borrello, Ivan M. Levitsky, Hyam I. Stock, Wendy Sher, Dorie Qin, Lu DeAngelo, Daniel J. Alyea, Edwin P. Stone, Richard M. Damon, Lloyd E. Linker, Charles A. Maslyar, Daniel J. Hege, Kristen M. TI Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML) SO BLOOD LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID BONE-MARROW-TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; AUGMENTS ANTITUMOR IMMUNITY; REFRACTORY PROSTATE-CANCER; GROUP-B; INTENSIVE CHEMOTHERAPY; PANCREATIC-CANCER; 1ST REMISSION AB Preclinical models have demonstrated the efficacy of granulocyte-macrophage colony-stimulating factor-secreting cancer immunotherapies (GVAX platform) accompanied by immunotherapy-primed lymphocytes after autologous stem cell transplantation in hematologic malignancies. We conducted a phase 2 study of this combination in adult patients with acute myeloid leukemia. Immunotherapy consisted of autologous leukemia cells admixed with granulocyte-macrophage colony-stimulating factor-secreting K562 cells. "Primed" lymphocytes were collected after a single pretransplantation dose of immunotherapy and reinfused with the stem cell graft. Fifty-four subjects were enrolled; 46 (85%) achieved a complete remission, and 28 (52%) received the pretransplantation immunotherapy. For all patients who achieved complete remission, the 3-year relapse-free survival (RFS) rate was 47.4% and overall survival was 57.4%. For the 28 immunotherapy-treated patients, the RFS and overall survival rates were 61.8% and 73.4%, respectively. Posttreatment induction of delayed-type hypersensitivity reactions to autologous leukemia cells was associated with longer 3-year RFS rate (100% vs 48%). Minimal residual disease was monitored by quantitative analysis of Wilms tumor-1 (WT1), a leukemia-associated gene. A decrease in WT1 transcripts in blood was noted in 69% of patients after the first immunotherapy dose and was also associated with longer 3-year RFS (61% vs 0%). In conclusion, immunotherapy in combination with primed lymphocytes and autologous stem cell transplantation shows encouraging signals of potential activity in acute myeloid leukemia (Clinical-Trials. gov: NCT00116467). (Blood. 2009; 114:1736-1745) C1 [Levitsky, Hyam I.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [Stock, Wendy; Sher, Dorie] Univ Chicago, Chicago, IL 60637 USA. [DeAngelo, Daniel J.; Alyea, Edwin P.; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Damon, Lloyd E.; Linker, Charles A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Maslyar, Daniel J.; Hege, Kristen M.] Cell Genesys, San Francisco, CA USA. RP Levitsky, HI (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St,Room 4M51, Baltimore, MD 21231 USA. EM hy@jhmi.edu FU NCI NIH HHS [P01 CA015396, P30 CA016672, 2P01CA15396-23] NR 37 TC 51 Z9 52 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 27 PY 2009 VL 114 IS 9 BP 1736 EP 1745 DI 10.1182/blood-2009-02-205278 PG 10 WC Hematology SC Hematology GA 488WI UT WOS:000269380600008 PM 19556425 ER PT J AU Fernandes, MS Reddy, MM Gonneville, JR Deroo, SC Podar, K Griffin, JD Weinstock, DM Sattler, M AF Fernandes, Margret S. Reddy, Mamatha M. Gonneville, Jeffrey R. DeRoo, Scott C. Podar, Klaus Griffin, James D. Weinstock, David M. Sattler, Martin TI BCR-ABL promotes the frequency of mutagenic single-strand annealing DNA repair SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; MAMMALIAN-CELLS; BREAK REPAIR; V(D)J RECOMBINATION; TARGETED THERAPIES; HOMOLOGOUS REPAIR; STEM-CELLS; BCR/ABL; RESISTANCE AB Intracellular oxidative stress in cells transformed by the BCR-ABL oncogene is associated with increased DNA double-strand breaks. Imprecise repair of these breaks can result in the accumulation of mutations, leading to therapy-related drug resistance and disease progression. Using several BCR-ABL model systems, we found that BCR-ABL specifically promotes the repair of double-strand breaks through single-strand annealing (SSA), a mutagenic pathway that involves sequence repeats. Moreover, our results suggest that mutagenic SSA repair can be regulated through the interplay between BCR-ABL and extrinsic growth factors. Increased SSA activity required Y177 in BCR-ABL, as well as a functional PI3K and Ras pathway downstream of this site. Furthermore, our data hint at a common pathway for DSB repair whereby BCR-ABL, Tel-ABL, Tel-PDGFR, FLT3-ITD, and Jak2V617F all increase mutagenic repair. This increase in SSA may not be sufficiently suppressed by tyrosine kinase inhibitors in the stromal microenvironment. Therefore, drugs that target growth factor receptor signaling represent potential therapeutic agents to combat tyrosine kinase-induced genomic instability. (Blood. 2009; 114:1813-1819) C1 [Fernandes, Margret S.; Reddy, Mamatha M.; Gonneville, Jeffrey R.; DeRoo, Scott C.; Podar, Klaus; Griffin, James D.; Weinstock, David M.; Sattler, Martin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fernandes, Margret S.; Reddy, Mamatha M.; Podar, Klaus; Griffin, James D.; Weinstock, David M.; Sattler, Martin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fernandes, Margret S.; Reddy, Mamatha M.; Podar, Klaus; Griffin, James D.; Weinstock, David M.; Sattler, Martin] Harvard Univ, Sch Med, Boston, MA USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM martin_sattler@dfci.harvard.edu FU National Institutes of Health [CA134660-01, CA66996, CA36167, DK50654]; Leukemia & Lymphoma Society; American Cancer Society; US Department of Defense; Adams Barr Program in Innovative Cancer Research FX This work was supported in part by the National Institutes of Health (grants CA134660-01, M. S.; CA66996, CA36167, and DK50654, J. D. G.), the Leukemia & Lymphoma Society (SCOR grant, J. D. G.), the American Cancer Society, the US Department of Defense, and the Adams Barr Program in Innovative Cancer Research (M. S.). NR 44 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 27 PY 2009 VL 114 IS 9 BP 1813 EP 1819 DI 10.1182/blood-2008-07-172148 PG 7 WC Hematology SC Hematology GA 488WI UT WOS:000269380600017 PM 19571320 ER PT J AU Ancuta, P Liu, KY Misra, V Wacleche, VS Gosselin, A Zhou, XB Gabuzda, D AF Ancuta, Petronela Liu, Kuang-Yu Misra, Vikas Wacleche, Vanessa Sue Gosselin, Annie Zhou, Xiaobo Gabuzda, Dana TI Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+and CD16-monocyte subsets SO BMC GENOMICS LA English DT Review ID BLOOD MONOCYTE SUBSETS; DENDRITIC CELL SUBSETS; GROWTH-FACTOR-BETA; WISKOTT-ALDRICH SYNDROME; TRANS-RETINOIC ACID; CD4(+) T-CELLS; ANTIGEN PRESENTATION; IN-VITRO; HEMATOPOIETIC-CELLS; PROGENITOR CELLS AB Background: Human peripheral blood monocytes (Mo) consist of subsets distinguished by expression of CD16 (FC gamma RIII) and chemokine receptors. Classical CD16(-) Mo express CCR2 and migrate in response to CCL2, while a minor CD16(+) Mo subset expresses CD16 and CX3CR1 and migrates into tissues expressing CX3CL1. CD16(+) Mo produce pro-inflammatory cytokines and are expanded in certain inflammatory conditions including sepsis and HIV infection. Results: To gain insight into the developmental relationship and functions of CD16(+) and CD16(-) Mo, we examined transcriptional profiles of these Mo subsets in peripheral blood from healthy individuals. Of 16,328 expressed genes, 2,759 genes were differentially expressed and 228 and 250 were >2-fold upregulated and downregulated, respectively, in CD16(+) compared to CD16(-) Mo. CD16(+) Mo were distinguished by upregulation of transcripts for dendritic cell (DC) (SIGLEC10, CD43, RARA) and macrophage (M Phi) (CSF1R/CD115, MafB, CD97, C3aR) markers together with transcripts relevant for DC-T cell interaction (CXCL16, ICAM-2, LFA-1), cell activation (LTB, TNFRSF8, LST1, IFITM1-3, HMOX1, SOD-1, WARS, MGLL), and negative regulation of the cell cycle (CDKN1C, MTSS1), whereas CD16(-) Mo were distinguished by upregulation of transcripts for myeloid (CD14, MNDA, TREM1, CD1d, C1qR/CD93) and granulocyte markers (FPR1, GCSFR/CD114, S100A8-9/12). Differential expression of CSF1R, CSF3R, C1QR1, C3AR1, CD1d, CD43, CXCL16, and CX3CR1 was confirmed by flow cytometry. Furthermore, increased expression of RARA and KLF2 transcripts in CD16(+) Mo coincided with absence of cell surface cutaneous lymphocyte associated antigen (CLA) expression, indicating potential imprinting for non-skin homing. Conclusion: These results suggest that CD16(+) and CD16(-) Mo originate from a common myeloid precursor, with CD16(+) Mo having a more M Phi - and DC-like transcription program suggesting a more advanced stage of differentiation. Distinct transcriptional programs, together with their recruitment into tissues via different mechanisms, also suggest that CD16(+) and CD16(-) Mo give rise to functionally distinct DC and M Phi in vivo. C1 [Ancuta, Petronela; Wacleche, Vanessa Sue; Gosselin, Annie] Univ Montreal, CRCHUM, INSERM, U743, Montreal, PQ, Canada. [Liu, Kuang-Yu] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Misra, Vikas; Gabuzda, Dana] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Zhou, Xiaobo] Methodist Hosp, Res Inst, Weill Cornell Med Coll, Dept Radiol, Houston, TX 77030 USA. RP Ancuta, P (reprint author), Univ Montreal, CRCHUM, INSERM, U743, Montreal, PQ, Canada. EM petronela.ancuta@umontreal.ca; kuangyu.liu@gmail.com; vikas_misra@dfci.harvard.edu; vanessa.sue.wacleche@umontreal.ca; annie.gosselin.chum@gmail.com; XZhou@tmhs.org; dana_gabuzda@dfci.harvard.edu FU NIH [DA16549, DA36222]; ANRS; Harvard University Center for AIDS Research; DFCI/Harvard Center for Cancer Research; FRSQ; INSERM; [CIHR/MOP82849] FX We thank Trent Rector for help with performing Affymetrix microarrays and initial data analysis (Biopolymers Facility at Harvard Medical School), Tao Lu for providing advice and technical expertise for real time RT-PCR, Elaine Thomas for helpful discussions, and Bruce Yankner for advice on statistical analysis of microarray results and valuable discussions. This work was supported by NIH DA16549 and DA36222 to DG and CIHR/MOP82849 and ANRS grants to PA. Core facilities were supported by the Harvard University Center for AIDS Research and DFCI/Harvard Center for Cancer Research grants. PA is a New Investigator Awardee from FRSQ and INSERM. NR 112 TC 111 Z9 113 U1 0 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD AUG 27 PY 2009 VL 10 AR 403 DI 10.1186/1471-2164-10-403 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 501PQ UT WOS:000270394200001 PM 19712453 ER PT J AU Sankaran, VG Xu, J Ragoczy, T Ippolito, GC Walkley, CR Maika, SD Fujiwara, Y Ito, M Groudine, M Bender, MA Tucker, PW Orkin, SH AF Sankaran, Vijay G. Xu, Jian Ragoczy, Tobias Ippolito, Gregory C. Walkley, Carl R. Maika, Shanna D. Fujiwara, Yuko Ito, Masafumi Groudine, Mark Bender, M. A. Tucker, Philip W. Orkin, Stuart H. TI Developmental and species-divergent globin switching are driven by BCL11A SO NATURE LA English DT Article ID YEAST ARTIFICIAL CHROMOSOME; LOCUS-CONTROL REGION; TRANSGENIC MICE; FETAL-HEMOGLOBIN; GENE-EXPRESSION; FUNCTIONAL-ANALYSIS; EVO-DEVO; TRANSCRIPTION; CELLS; MOUSE AB The contribution of changes in cis-regulatory elements or trans-acting factors to interspecies differences in gene expression is not well understood. The mammalian beta-globin loci have served as a model for gene regulation during development. Transgenic mice containing the human beta-globin locus, consisting of the linked embryonic (epsilon), fetal (gamma) and adult (beta) genes, have been used as a system to investigate the temporal switch from fetal to adult haemoglobin, as occurs in humans. Here we show that the human gamma-globin (HBG) genes in these mice behave as murine embryonic globin genes, revealing a limitation of the model and demonstrating that critical differences in the trans-acting milieu have arisen during mammalian evolution. We show that the expression of BCL11A, a repressor of human gamma-globin expression identified by genome-wide association studies, differs between mouse and human. Developmental silencing of the mouse embryonic globin and human gamma-globin genes fails to occur in mice in the absence of BCL11A. Thus, BCL11A is a critical mediator of species-divergent globin switching. By comparing the ontogeny of beta-globin gene regulation in mice and humans, we have shown that alterations in the expression of a trans-acting factor constitute a critical driver of gene expression changes during evolution. C1 [Sankaran, Vijay G.; Xu, Jian; Walkley, Carl R.; Fujiwara, Yuko; Orkin, Stuart H.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. [Sankaran, Vijay G.; Xu, Jian; Walkley, Carl R.; Fujiwara, Yuko; Orkin, Stuart H.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Xu, Jian; Fujiwara, Yuko; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Ragoczy, Tobias; Groudine, Mark; Bender, M. A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Ippolito, Gregory C.; Maika, Shanna D.; Tucker, Philip W.] Univ Texas Austin, Inst Mol & Cellular Biol, Austin, TX 78712 USA. [Ito, Masafumi] Nagoya First Hosp, Dept Pathol, Nagoya, Aichi, Japan. [Groudine, Mark] Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. [Bender, M. A.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu OI Walkley, Carl/0000-0002-4784-9031 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); National Cancer Institute; Howard Hughes Medical Institute (HHMI); Leukemia & Lymphoma Society; American Society of Hematology; Helen Hay Whitney Foundation; NCI postdoctoral fellowship FX We are grateful to K. Peterson and H. Fedosyuk for providing beta-locus mice, K. Gaensler for the A20 and A85 strains of b- locus mice, and T. Jacks for providing the K- RasG12D mice. We thank J. Palis and P. Kingsley for providing mouse embryonic globin antibodies, H. Mikkola and B. Van Handel for providing sorted human samples, and R. Byron and A. Telling for technical support. Wethank L. Zon, K. McGrath, P. Kingsley, J. Palis, M. Kowalczyk and T. Menne for advice and discussions. This work was supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (S.H.O. and M. G.) and the National Cancer Institute ( P. W. T.). S. H. O. is an Investigator of the Howard Hughes Medical Institute (HHMI). C. R. W. is a special fellow of the Leukemia & Lymphoma Society. T. R. is supported by a fellowship from the American Society of Hematology. J. X. is an HHMI fellow of the Helen Hay Whitney Foundation. V. G. S. is supported by a Medical Scientist Training Program Award from the NIH and G. C. I. is supported by a NCI postdoctoral fellowship. NR 38 TC 173 Z9 181 U1 6 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 27 PY 2009 VL 460 IS 7259 BP 1093 EP U50 DI 10.1038/nature08243 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487YE UT WOS:000269314000030 PM 19657335 ER PT J AU Utikal, J Polo, JM Stadtfeld, M Maherali, N Kulalert, W Walsh, RM Khalil, A Rheinwald, JG Hochedlinger, K AF Utikal, Jochen Polo, Jose M. Stadtfeld, Matthias Maherali, Nimet Kulalert, Warakorn Walsh, Ryan M. Khalil, Adam Rheinwald, James G. Hochedlinger, Konrad TI Immortalization eliminates a roadblock during cellular reprogramming into iPS cells SO NATURE LA English DT Article ID PLURIPOTENT STEM-CELLS; TUMOR SUPPRESSION; SOMATIC-CELLS; INK4A LOCUS; LIFE-SPAN; IN-VIVO; FIBROBLASTS; MOUSE; GENERATION; EFFICIENCY AB The overexpression of defined transcription factors in somatic cells results in their reprogramming into induced pluripotent stem (iPS) cells(1-3). The extremely low efficiency and slow kinetics of in vitro reprogramming suggest that further rare events are required to generate iPS cells. The nature and identity of these events, however, remain elusive. We noticed that the reprogramming potential of primary murine fibroblasts into iPS cells decreases after serial passaging and the concomitant onset of senescence. Consistent with the notion that loss of replicative potential provides a barrier for reprogramming, here we show that cells with low endogenous p19(Arf) (encoded by the Ink4a/Arf locus, also known as Cdkn2a locus) protein levels and immortal fibroblasts deficient in components of the Arf-Trp53 pathway yield iPS cell colonies with up to threefold faster kinetics and at a significantly higher efficiency than wild-type cells, endowing almost every somatic cell with the potential to form iPS cells. Notably, the acute genetic ablation of Trp53 (also known as p53) in cellular sub-populations that normally fail to reprogram rescues their ability to produce iPS cells. Our results show that the acquisition of immortality is a crucial and rate-limiting step towards the establishment of a pluripotent state in somatic cells and underscore the similarities between induced pluripotency and tumorigenesis. C1 [Utikal, Jochen; Polo, Jose M.; Stadtfeld, Matthias; Maherali, Nimet; Kulalert, Warakorn; Walsh, Ryan M.; Khalil, Adam; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Utikal, Jochen; Polo, Jose M.; Stadtfeld, Matthias; Maherali, Nimet; Kulalert, Warakorn; Walsh, Ryan M.; Khalil, Adam; Hochedlinger, Konrad] Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. [Utikal, Jochen; Polo, Jose M.; Stadtfeld, Matthias; Maherali, Nimet; Kulalert, Warakorn; Walsh, Ryan M.; Khalil, Adam; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Utikal, Jochen] Univ Heidelberg, Univ Med Ctr Mannheim, Dept Dermatol Venereol & Allergol, D-68135 Mannheim, Germany. [Maherali, Nimet] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Rheinwald, James G.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Rheinwald, James G.] Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu OI Utikal, Jochen/0000-0001-5316-0241; Polo, Jose M/0000-0002-2531-778X; Stadtfeld, Matthias/0000-0002-5852-9906 FU Mildred Scheel Foundation; ECOR fellowship; Schering Foundation; NIH Skin Disease Research Center Grant; Natural Sciences and Engineering Council of Canada; NIH Director's Innovator Award; Harvard Stem Cell Institute; Kimmel Foundation and the V Foundation FX We thank M. Roussel and C. Sherr for providing us with Arf-GFP cells, D. C. Bennett and E. Sviderskaya for sharing Melan A cells, and A. Ventura and T. Jacks for tail biopsies of conditional Trp53-mutant mice. We also thank A. Tzatsos and N. Bardeesy for suggestions, for critical reading of the manuscript and for providing Ink4a/Arf2/2 MEFs. We are grateful to P. Follett for blastocyst injections and L. Prickett and K. Folz-Donahue for assistance with FACS. J. U. was supported by a postdoctoral fellowship from the Mildred Scheel Foundation, J. M. P. by an ECOR fellowship, and M. S. by a fellowship from the Schering Foundation. J. G. R. was supported by an NIH Skin Disease Research Center Grant. N. M. was supported by a graduated scholarship from the Natural Sciences and Engineering Council of Canada. Support to K. H. came from the NIH Director's Innovator Award, the Harvard Stem Cell Institute, the Kimmel Foundation and the V Foundation. NR 29 TC 496 Z9 516 U1 6 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 27 PY 2009 VL 460 IS 7259 BP 1145 EP U112 DI 10.1038/nature08285 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487YE UT WOS:000269314000042 PM 19668190 ER PT J AU Kajimura, S Seale, P Kubota, K Lunsford, E Frangioni, JV Gygi, SP Spiegelman, BM AF Kajimura, Shingo Seale, Patrick Kubota, Kazuishi Lunsford, Elaine Frangioni, John V. Gygi, Steven P. Spiegelman, Bruce M. TI Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex SO NATURE LA English DT Article ID ADIPOSE-TISSUE; C/EBP-BETA; ADIPOCYTE DIFFERENTIATION; OLIGONUCLEOTIDE ARRAYS; ADULT HUMANS; MICE LACKING; PPAR-GAMMA; PROTEIN; GENE; EXPRESSION AB Brown adipose cells are specialized to dissipate chemical energy in the form of heat, as a physiological defence against cold and obesity(1). PRDM16 (PR domain containing 16) is a 140 kDa zinc finger protein that robustly induces brown fat determination and differentiation(2). Recent data suggests that brown fat cells arise in vivo from a Myf5-positive, myoblastic lineage by the action of PRDM16 (ref. 3); however, the molecular mechanisms responsible for this developmental switch is unclear. Here we show that PRDM16 forms a transcriptional complex with the active form of C/EBP-beta ( also known as LAP), acting as a critical molecular unit that controls the cell fate switch from myoblastic precursors to brown fat cells. Forced expression of PRDM16 and C/EBP-beta is sufficient to induce a fully functional brown fat program in naive fibroblastic cells, including skin fibroblasts from mouse and man. Transplantation of fibroblasts expressing these two factors into mice gives rise to an ectopic fat pad with the morphological and biochemical characteristics of brown fat. Like endogenous brown fat, this synthetic brown fat tissue acts as a sink for glucose uptake, as determined by positron emission tomography with fluorodeoxyglucose. These data indicate that the PRDM16-C/EBP-beta complex initiates brown fat formation from myoblastic precursors, and may provide opportunities for the development of new therapeutics for obesity and type-2 diabetes. C1 [Kajimura, Shingo; Seale, Patrick; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kajimura, Shingo; Seale, Patrick; Kubota, Kazuishi; Gygi, Steven P.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Lunsford, Elaine; Frangioni, John V.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU AHA [0930125N]; National Institutes of Health ( NIH) [DK081605, HG3456, GM67945]; Picower Foundation [DK31405]; NIH/NCRR [S10-RR-023010] FX We are grateful to S. R. Farmer, J. Rheinwald and P. F. Johnson for providing cells and other reagents, R. Gupta for his critical comments on the manuscript, and J. Y. Choi and E. Naseri for their assistance. S. K. is supported by AHA scientist development grant (0930125N). P. S. is supported by a National Institutes of Health ( NIH) grant (DK081605). This work was supported by grants from the Picower Foundation and the NIH (DK31405) to B. M. S., NIH HG3456 and GM67945 to S. P. G., and NIH/NCRR shared instrumentation grant S10-RR-023010. NR 36 TC 290 Z9 314 U1 6 U2 45 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 27 PY 2009 VL 460 IS 7259 BP 1154 EP U125 DI 10.1038/nature08262 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487YE UT WOS:000269314000044 PM 19641492 ER PT J AU Abramson, JS Digumarthy, S Ferry, JA AF Abramson, Jeremy S. Digumarthy, Subba Ferry, Judith A. TI A Woman with Fever, Rash, and Lymphadenopathy Angioimmunoblastic T-cell lymphoma. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NON-HODGKINS-LYMPHOMA; CLINICAL-FEATURES; KIKUCHIS-DISEASE; IMMUNOBLASTIC LYMPHADENOPATHY; HISTOLOGIC SUBTYPES; COMPLETE REMISSION; NATURAL-HISTORY; INSECT STINGS; HIV-INFECTION; TRANSPLANTATION C1 [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Digumarthy, Subba] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ferry, Judith A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Abramson, Jeremy S.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Digumarthy, Subba] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Ferry, Judith A.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 50 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 27 PY 2009 VL 361 IS 9 BP 900 EP 911 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 487XV UT WOS:000269312700012 PM 19710489 ER PT J AU Morrow, DA AF Morrow, David A. TI Clinical Application of Sensitive Troponin Assays. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MYOCARDIAL-INFARCTION; NATIONAL ACADEMY; MARKERS C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Thrombolysis Myocardial Infarct TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 48 Z9 51 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 27 PY 2009 VL 361 IS 9 BP 913 EP 915 DI 10.1056/NEJMe0905790 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 487XV UT WOS:000269312700013 PM 19710490 ER PT J AU Cooper, M Deering, KL Slakey, DP Harshaw, Q Arcona, S McCann, EL Rasetto, FA Florman, SS AF Cooper, Matthew Deering, Kathleen L. Slakey, Douglas P. Harshaw, Qing Arcona, Stephen McCann, Erin L. Rasetto, Flavia A. Florman, Sander S. TI Comparing Outcomes Associated With Dose Manipulations of Enteric-Coated Mycophenolate Sodium Versus Mycophenolate Mofetil in Renal Transplant Recipients SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat DE Gastrointestinal adverse events; Mycophenolate sodium; Mycophenolate mofetil; Renal transplant; Rejection-risk ID GASTROINTESTINAL COMPLICATIONS; CONVERSION; ACID; IMPACT; MMF AB Background. This study assessed the incidence of reported gastrointestinal (GI) complications in patients treated with enteric-coated mycophenolate sodium (EC-MPS) versus mycophenolate mofetil (MMF) and to examine the impact of dose manipulations on biopsy-proven acute rejection (BPAR). Methods. A retrospective study was conducted in 379 renal transplant recipients initiated on EC-MPS or MMF through 3-months posttransplant between the years of 2001 to 2007. Descriptive univariate analyses were used for comparisons of baseline characteristics and outcome measures between the cohorts. A Cox proportional hazards model was used to evaluate the time to a first BPAR event. Results. GI complications occurred at an incidence of 52.8% and 48.9% in the EC-MPS and MMF cohorts, respectively (NS). Patients requiring dose manipulations due to GI complications were 19.7% with EC-MPS and 25.3% with MMF (NS). The mean equimolar dose reduction below 2000 mg was 930 +/- 292.13 mg with EC-MPS and 933 +/- 173.95 mg with MMF (NS). Patients treated with EC-MPS experienced significantly fewer BPAR episodes than those treated with MMF (14% EC-MPS vs. 23.1% MMF; P=0.0221). Conclusions. in this study, EC-MPS had a similar incidence of GI complications and dose manipulations compared with MMF. Despite similar GI complication rates and dose manipulations, treatment with EC-MPS seemed to result in a lower incidence of BPAR. Based on these observations, more studies need to be conducted to evaluate risks for BPAR relating to mycophenolic acid product. C1 [Cooper, Matthew] Univ Maryland, Sch Med, Div Transplantat, Baltimore, MD 21201 USA. [Deering, Kathleen L.; Harshaw, Qing] Hlth Econ & Outcomes Res, Oak Brook, IL USA. [Slakey, Douglas P.; Florman, Sander S.] Tulane Univ Med Ctr Hosp & Clin, Div Transplantat, New Orleans, LA USA. [Arcona, Stephen] Novartis Pharmaceut, Evidence Based Med, E Hanover, NJ USA. [McCann, Erin L.] VA Pittsburgh Healthcare Syst, Dept Pharm, Pittsburgh, PA USA. [McCann, Erin L.; Rasetto, Flavia A.] Univ Maryland, Med Syst, Dept Pharm, Baltimore, MD 21201 USA. RP Cooper, M (reprint author), Univ Maryland, Sch Med, Div Transplantat, 29 S Greene St,Room 200, Baltimore, MD 21201 USA. EM mcooper@smail.umaryland.edu NR 19 TC 19 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 2009 VL 88 IS 4 BP 514 EP 520 DI 10.1097/TP.0b013e3181b0e65e PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 487UT UT WOS:000269303200011 PM 19696634 ER PT J AU Nanda, A Chen, MH Braccioforte, MH Moran, BJ D'Amico, AV AF Nanda, Akash Chen, Ming-Hui Braccioforte, Michelle H. Moran, Brian J. D'Amico, Anthony V. TI Hormonal Therapy Use for Prostate Cancer and Mortality in Men With Coronary Artery Disease-Induced Congestive Heart Failure or Myocardial Infarction SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; EXTERNAL-BEAM RADIOTHERAPY; RADIATION-THERAPY; DEFINITIVE RADIOTHERAPY; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; BODY-COMPOSITION; TASK-FORCE; BRACHYTHERAPY AB Context Hormonal therapy (HT) when added to radiation therapy (RT) for treating unfavorable-risk prostate cancer leads to an increase in survival except possibly in men with moderate to severe comorbidity. However, it is unknown which comorbid conditions eliminate this survival benefit. Objective To assess whether neoadjuvant HT use affects the risk of all-cause mortality in men with prostate cancer and coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI), CAD risk factors, or no comorbidity. Design, Setting, and Patients A total of 5077 men (median age, 69.5 years) with localized or locally advanced prostate cancer were consecutively treated with or without a median of 4 months of neoadjuvant HT followed by RT at a suburban cancer center between 1997 and 2006 and were followed up until July 1, 2008. Cox regression multivariable analyses were performed assessing whether neoadjuvant HT use affected the risk of all-cause mortality, adjusting for age, year and type of RT, treatment propensity score, and known prostate cancer prognostic factors in each comorbidity group. Main Outcome Measure Risk of all-cause mortality. Results Neoadjuvant HT use was not associated with an increased risk of all-cause mortality in men with no comorbidity (9.6% vs 6.7%, adjusted hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.72-1.32; P=.86) or a single CAD risk factor (10.7% vs 7.0%, adjusted HR, 1.04; 95% CI, 0.75-1.43; P=.82) after median follow-ups of 5.0 and 4.4 years, respectively. However, for men with CAD-induced CHF or MI, after a median follow-up of 5.1 years, neoadjuvant HT use was significantly associated with an increased risk of all-cause mortality (26.3% vs 11.2%, adjusted HR, 1.96; 95% CI, 1.04-3.71; P=.04). Conclusion Neoadjuvant HT use is significantly associated with an increased risk of all-cause mortality among men with a history of CAD-induced CHF or MI but not among men with no comorbidity or a single CAD risk factor. JAMA. 2009; 302(8): 866-873 C1 [Nanda, Akash] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dana Farber Canc Inst, Boston, MA 02115 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Braccioforte, Michelle H.; Moran, Brian J.] Prostate Canc Fdn Chicago, Westmont, IL USA. RP Nanda, A (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dana Farber Canc Inst, 75 Francis St,ASB1 L2, Boston, MA 02115 USA. EM ananda@partners.org NR 46 TC 157 Z9 161 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 26 PY 2009 VL 302 IS 8 BP 866 EP 873 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 487GN UT WOS:000269260100020 PM 19706860 ER PT J AU Bhatt, DL AF Bhatt, Deepak L. TI Tailoring Antiplatelet Therapy Based on Pharmacogenomics How Well Do the Data Fit? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PERCUTANEOUS CORONARY INTERVENTION; OF-FUNCTION POLYMORPHISM; ATHEROTHROMBOTIC EVENTS; CLOPIDOGREL RESISTANCE; GENETIC-DETERMINANTS; STENT THROMBOSIS; ASPIRIN; OUTCOMES; RISK C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 75 Francis St,PBB 146, Boston, MA 02115 USA. EM dlbhattmd@alum.mit.edu NR 20 TC 29 Z9 30 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 26 PY 2009 VL 302 IS 8 BP 896 EP 897 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 487GN UT WOS:000269260100026 PM 19706866 ER PT J AU Liu, CH Ren, JQ Yang, JS Liu, CM Mandeville, JB Rosen, BR Bhide, PG Yanagawa, Y Liu, PK AF Liu, Christina H. Ren, Jia Q. Yang, Jinsheng Liu, Charng-ming Mandeville, Joseph B. Rosen, Bruce R. Bhide, Pradeep G. Yanagawa, Yuchio Liu, Philip K. TI DNA-Based MRI Probes for Specific Detection of Chronic Exposure to Amphetamine in Living Brains SO JOURNAL OF NEUROSCIENCE LA English DT Article ID FOS MESSENGER-RNA; VENTRAL TEGMENTAL AREA; EARLY GENE-EXPRESSION; C-FOS; DELTA-FOSB; CHRONIC COCAINE; ANTISENSE OLIGODEOXYNUCLEOTIDE; BEHAVIORAL SENSITIZATION; ENVIRONMENTAL CONTEXT; NUCLEUS-ACCUMBENS AB We designed phosphorothioate-modified DNA probes linked to superparamagnetic iron oxide nanoparticles (SPION) for in vivo magnetic resonance imaging (MRI) of fosB and Delta fosB mRNA after amphetamine (AMPH) exposure in mice. Specificity of both the fosB and Delta fosB probes was verified by in vitro reverse transcriptase-PCR amplification to a single fragment of total cDNA obtained from acutely AMPH-exposed mouse brains. We confirmed time-dependent uptake and retention profiles of both probes in neurons of GAD67-green fluorescent protein knock-in mice. MRI signal of SPION-labeled fosB probe delivered via intracerebroventricular route was elevated in both acutely and chronically AMPH-exposed mice; the signal was suppressed by dopaminergic receptor antagonist pretreatment. SPION-labeled Delta fosB probe signal elevation occurred only in chronically AMPH-exposed mice. The in vivo target specificity of these probes permits reliable MRI visualization of AMPH-induced differential elevations of fosB and Delta fosB mRNA in living brains. C1 [Liu, Christina H.; Ren, Jia Q.; Liu, Charng-ming; Liu, Philip K.] Massachusetts Gen Hosp, Dept Radiol, Lab Gene Transcript Targeting Imaging & Repair, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Yang, Jinsheng] Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. [Bhide, Pradeep G.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Yanagawa, Yuchio] Gunma Univ, Grad Sch Med, Maebashi, Gumma 3718511, Japan. RP Liu, PK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Lab Gene Transcript Targeting Imaging & Repair, AA Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM philipl@nmr.mgh.harvard.edu OI Liu, Christina/0000-0002-5723-177X; Bhide, Pradeep/0000-0003-4236-9415 FU American Heart Association [09GRNT2060416]; National Institutes of Health [R01EB002066, R03EB008134, R21DA024235, R01DA026108, R01NS045845, R21NS057556, R01DA020796, P30NS045776]; National Center for Research Resources [P41RR014075] FX This project was supported by grants from American Heart Association (09GRNT2060416), National Institutes of Health (R01EB002066 to B. R. R., R03EB008134 to J. B. M., R21DA024235 and R01DA026108 to C. H. L., R01NS045845 and R21NS057556 to P. K. L., and R01DA020796 and P30NS045776 to P. G. B.), and National Center for Research Resources (P41RR014075 to B. R. R.). We thank Dr. Yusaku Nakabeppu (Kyushu University, Japan) for cloned cDNA of fosB and Delta fosB, and Dr. Helen D'Arceuil and Ms. N. Eusemann for suggestions and excellent editing. Two patent applications have been submitted on this technology: (1) Imaging nucleic acids (US 60-603907) and (2) Targeting brain cells via ophthalmic delivery which included SPION-Delta fosB probe (US 60-962499). NR 44 TC 13 Z9 13 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 AUG 26 PY 2009 VL 29 IS 34 BP 10663 EP 10670 DI 10.1523/JNEUROSCI.2167-09.2009 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 487ZJ UT WOS:000269317900020 PM 19710318 ER PT J AU Ekstrom, LB Roelfsema, PR Arsenault, JT Kolster, H Vanduffel, W AF Ekstrom, Leeland B. Roelfsema, Pieter R. Arsenault, John T. Kolster, Hauke Vanduffel, Wim TI Modulation of the Contrast Response Function by Electrical Microstimulation of the Macaque Frontal Eye Field SO JOURNAL OF NEUROSCIENCE LA English DT Article ID EXTRASTRIATE VISUAL-CORTEX; SUPERIOR TEMPORAL SULCUS; COVERT SPATIAL ATTENTION; CORTICAL CONNECTIONS; PERCEPTUAL SENSITIVITY; NORMALIZATION MODEL; RECEPTIVE-FIELD; STRIATE CORTEX; AREA MT; MONKEY AB Spatial attention influences representations in visual cortical areas as well as perception. Some models predict a contrast gain, whereas others a response or activity gain when attention is directed to a contrast-varying stimulus. Recent evidence has indicated that microstimulating the frontal eye field (FEF) can produce modulations of cortical area 4 neuronal firing rates that resemble spatial attention-like effects, and we have shown similar modulations of functional magnetic resonance imaging (fMRI) activity throughout the visual system. Here, we used fMRI in awake, fixating monkeys to first measure the response in 12 visual cortical areas to stimuli of varying luminance contrast. Next, we simultaneously microstimulated subregions of the FEF with movement fields that overlapped the stimulus locations and measured how microstimulation modulated these contrast response functions (CRFs) throughout visual cortex. In general, we found evidence for a nonproportional scaling of the CRF under these conditions, resembling a contrast gain effect. Representations of low-contrast stimuli were enhanced by stimulation of the FEF below the threshold needed to evoke saccades, whereas high-contrast stimuli were unaffected or in some areas even suppressed. Furthermore, we measured a characteristic spatial pattern of enhancement and suppression across the cortical surface, from which we propose a simple schematic of this contrast-dependent fMRI response. C1 [Ekstrom, Leeland B.; Arsenault, John T.; Kolster, Hauke; Vanduffel, Wim] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Vanduffel, Wim] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. [Ekstrom, Leeland B.] Harvard Massachusetts Inst Technol, Div Hlth Sci, Cambridge, MA 02139 USA. [Ekstrom, Leeland B.] MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. [Roelfsema, Pieter R.] Inst Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Dept Vis & Cognit, NL-1105 BA Amsterdam, Netherlands. [Roelfsema, Pieter R.] Vrije Univ Amsterdam, Ctr Neurogenom & Cognit Res, Dept Integrat Neurophysiol, NL-1081 HV Amsterdam, Netherlands. [Arsenault, John T.; Kolster, Hauke; Vanduffel, Wim] Katholieke Univ Leuven, Sch Med, Lab Neuro Psychofysiol, B-3000 Louvain, Belgium. RP Vanduffel, W (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2300, Charlestown, MA 02129 USA. EM wim@nmr.mgh.harvard.edu RI Roelfsema, Pieter/J-6903-2013 OI Roelfsema, Pieter/0000-0002-1625-0034 FU Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship; Human Frontier Science Program Organization; Geneeskundige Stichting Koningin Elisabeth; Inter-University Attraction Pole 5/04; Excellence Financing/05/014; Geconcerteerde Onderzoeksacties [2005/18]; Fonds Wetenschappelijk Onderzoek-Vlaanderen [G.0.622.08]; European Union [FP7/2007-2013, F2-2008-200728]; National Institutes of Health [R01-EB000790]; National Science Foundation [BCS-0745436]; National Center for Research Resources [P41RR14075]; MIND Institute FX This work received support from a Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship, Human Frontier Science Program Organization, Geneeskundige Stichting Koningin Elisabeth, Inter-University Attraction Pole 5/04, Excellence Financing/05/014, Geconcerteerde Onderzoeksacties 2005/18, Fonds Wetenschappelijk Onderzoek-Vlaanderen G.0.622.08, European Union Grant FP7/2007-2013 #F2-2008-200728, National Institutes of Health Grant R01-EB000790, and National Science Foundation Grant BCS-0745436. The Martinos Center is supported by National Center for Research Resources Grant P41RR14075 and the MIND Institute. We thank H. Deng for animal training and care, G. Madan, T. van Kerkoerle, G. Bonmassar, and L. Wald for technical assistance, B. Rosen for advice and support, and C. Moore and R. Vogels for valuable comments. NR 72 TC 40 Z9 40 U1 2 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 AUG 26 PY 2009 VL 29 IS 34 BP 10683 EP 10694 DI 10.1523/JNEUROSCI.0673-09.2009 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 487ZJ UT WOS:000269317900022 PM 19710320 ER PT J AU Hernstadt, H Wang, SX Lim, G Mao, JR AF Hernstadt, Hayley Wang, Shuxing Lim, Grewo Mao, Jianren TI Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis SO BRAIN RESEARCH LA English DT Article DE Translocator protein 18 kDa; TSPO; Peripheral benzodiazepine receptor; Pain; Inflammation; Inflammatory pain; Arthritis; Spinal cord ID PERIPHERAL BENZODIAZEPINE-RECEPTOR; PROINFLAMMATORY CYTOKINE EXPRESSION; MITOCHONDRIAL INNER MEMBRANE; DIAZEPAM-BINDING INHIBITOR; NEUROPATHIC PAIN; CELL-PROLIFERATION; ENDOGENOUS LIGANDS; PATHOLOGICAL PAIN; GLIAL ACTIVATION; 18 KDA AB Translocator protein 18 kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. In the present study, we examined the hypothesis that TSPO is involved in the initiation and maintenance of inflammatory pain using a rat model of Complete Freund's Adjuvant (CFA)-induced monoarthritis of the tibio-tarsal joint. Immunohistochemistry was performed using Iba-1 (microglia), NeuN (neurons), anti-Glial Fibrillary Acidic Protein, GFAP (astrocytes) and anti-PBR (TSPO) on Days 1, 7 and 14 after CFA-induced arthritis. Rats with CFA-induced monoarthritis showed mechanical allodynia and thermal hyperalgesia on the ipsilateral hindpaw, which correlated with the increased TSPO expression in ipsilateral laminae I-II on all experimental days. Iba-1 expression in the ipsilateral dorsal horn was also increased on Days 7 and 14. Moreover, TSPO was colocalized with Iba-1, GFAP and NeuN within the spinal cord dorsal horn. The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain. (C) 2009 Elsevier B.V. All rights reserved. C1 [Hernstadt, Hayley; Wang, Shuxing; Lim, Grewo; Mao, Jianren] Harvard Univ, MGH Ctr Translat Pain Res, Dept Anesthesia & Crit Care, Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hernstadt, Hayley] Univ Melbourne, Fac Med Dent & Hlth Sci, Melbourne, Vic 3010, Australia. RP Mao, JR (reprint author), Harvard Univ, MGH Ctr Translat Pain Res, Dept Anesthesia & Crit Care, Sch Med,Massachusetts Gen Hosp, WACC 324, Boston, MA 02114 USA. EM wshuxing@partners.org; jmao@partners.org FU NIH R01 [DE18214, DE18S38, NS45681] FX This study was supported by NIH R01 grants DE18214, DE18S38, and NS45681. NR 83 TC 23 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 25 PY 2009 VL 1286 BP 42 EP 52 DI 10.1016/j.brainres.2009.06.043 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 488VI UT WOS:000269378000006 PM 19555675 ER PT J AU Chen, LL Blumm, N Christakis, NA Barabasi, AL Deisboeck, TS AF Chen, L. L. Blumm, N. Christakis, N. A. Barabasi, A-L Deisboeck, T. S. TI Cancer metastasis networks and the prediction of progression patterns SO BRITISH JOURNAL OF CANCER LA English DT Article ID BONE METASTASIS; MEDICARE CLAIMS; PROSTATE-CANCER; DISEASE; CLASSIFICATION; CELLS; COMORBIDITY; PERFORMANCE; MECHANISMS; DISCOVERY AB BACKGROUND: Metastasis patterns in cancer vary both spatially and temporally. Network modelling may allow the incorporation of the temporal dimension in the analysis of these patterns. METHODS: We used Medicare claims of 2 265 167 elderly patients aged >= 65 years to study the large-scale clinical pattern of metastases. We introduce the concept of a cancer metastasis network, in which nodes represent the primary cancer site and the sites of subsequent metastases, connected by links that measure the strength of co-occurrence. RESULTS: These cancer metastasis networks capture both temporal and subtle relational information, the dynamics of which differ between cancer types. Using these networks as entities on which the metastatic disease of individual patients may evolve, we show that they may be used, for certain cancer types, to make retrograde predictions of a primary cancer type given a sequence of metastases, as well as anterograde predictions of future sites of metastasis. CONCLUSION: Improvements over traditional techniques show that such a network-based modelling approach may be suitable for studying metastasis patterns. British Journal of Cancer (2009) 101, 749-758. doi:10.1038/sj.bjc.6605214 www.bjcancer.com (C) 2009 Cancer Research UK C1 [Chen, L. L.; Deisboeck, T. S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Harvard MIT HST, Complex Biosyst Modeling Lab, Charlestown, MA 02129 USA. [Blumm, N.; Barabasi, A-L] Northeastern Univ, Dept Phys, Ctr Network Sci, Boston, MA 02115 USA. [Christakis, N. A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Barabasi, A-L] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Harvard MIT HST, Complex Biosyst Modeling Lab, Charlestown, MA 02129 USA. EM DEISBOEC@helix.mgh.harvard.edu RI Christakis, Nicholas/C-3205-2009 FU NIH [113004, HG4233, A1070499-01, AG 17548]; Harvard-MIT (HST) Athinoula A Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital FX This work was supported in part by the NIH Grant CA 113004 (TSD, A-LB) and by the Harvard-MIT (HST) Athinoula A Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. Research at the Northeastern University was supported by the NIH Grants HG4233 (Centers of Excellence in Genomic Science) and A1070499-01. Development of the data set was supported by the NIH Grant AG 17548 (NAC). NR 45 TC 36 Z9 39 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD AUG 25 PY 2009 VL 101 IS 5 BP 749 EP 758 DI 10.1038/sj.bjc.6605214 PG 10 WC Oncology SC Oncology GA 487XW UT WOS:000269312800002 PM 19707203 ER PT J AU Egli, D Sandler, VM Shinohara, ML Cantor, H Eggan, K AF Egli, Dieter Sandler, Vladislav M. Shinohara, Mari L. Cantor, Harvey Eggan, Kevin TI Reprogramming after Chromosome Transfer into Mouse Blastomeres SO CURRENT BIOLOGY LA English DT Article ID PLURIPOTENT STEM-CELLS; NUCLEAR TRANSFER; 2-CELL EMBRYOS; MOTOR-NEURONS; SOMATIC-CELLS; DONOR CELLS; ZYGOTES; INVITRO; CLONING; ALS AB It is well known that oocyles can reprogram differentiated cells, allowing animal cloning by nuclear transfer. We have recently shown that fertilized zygotes retain reprogramming activities [1], suggesting that such activities might also persist in cleavage-stage embryos. Here, we used chromosome transplantation techniques to investigate whether the blastomeres of two-cell-stage mouse embryos can reprogram more differentiated cells. When chromosomes from one of the two blastomeres; were replaced with the chromosomes of an embryonic or CD4(+) T lymphocyte donor cell, we observed nuclear reprogramming and efficient contribution of the manipulated cell to the developing blastocyst. Embryos produced by this method could be used to derive stem cell lines and also developed to term, generating mosaic "cloned" animals. These results demonstrate that blastomeres retain reprogramming activities and support the notion that discarded human preimplantation embryos may be useful recipients for the production of genetically tailored human embryonic stem cell lines. C1 [Egli, Dieter; Sandler, Vladislav M.; Eggan, Kevin] Harvard Univ, Harvard Stem Cell Inst, Stowers Med Inst, Cambridge, MA 02140 USA. [Egli, Dieter; Sandler, Vladislav M.; Eggan, Kevin] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02140 USA. [Shinohara, Mari L.; Cantor, Harvey] Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Shinohara, Mari L.; Cantor, Harvey] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. RP Eggan, K (reprint author), Harvard Univ, Harvard Stem Cell Inst, Stowers Med Inst, 7 Divin Ave, Cambridge, MA 02140 USA. EM eggan@mcb.harvard.edu FU Harvard Stem Cell Institute; NIH [R01 HD045732-03, RO1 A1037562, T32 CA070083]; Stowers Medical Institute; Stan and Fiona Druckenmiller/New York Stem Cell Foundation; Catherine T. MacArthur Foundation FX We thank G. Birkhoff for assistance with the preparation of figures, I. Tabansky for assistance with the Imaris imaging software, and S. Noggle for critical reading of the manuscript. This work was supported by a seed grant from the Harvard Stem Cell Institute; NIH grants R01 HD045732-03 to K.E., RO1 A1037562 to H.C., and T32 CA070083 to M.L.S.; and the Stowers Medical Institute. D.E. is a Stan and Fiona Druckenmiller/New York Stem Cell Foundation postdoctoral fellow. K.E. is a fellow oftheJohn D. and Catherine T. MacArthur Foundation. NR 27 TC 25 Z9 25 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 25 PY 2009 VL 19 IS 16 BP 1403 EP 1409 DI 10.1016/j.cub.2009.06.065 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 488XM UT WOS:000269383700029 PM 19682906 ER PT J AU Kozanek, M Hosseini, A Liu, F Van de Velde, SK Gill, TJ Rubash, HE Li, GA AF Kozanek, Michal Hosseini, Ali Liu, Fang Van de Velde, Samuel K. Gill, Thomas J. Rubash, Harry E. Li, Guoan TI Tibiofemoral kinematics and condylar motion during the stance phase of gait SO JOURNAL OF BIOMECHANICS LA English DT Article DE Knee kinematics; Gait; Stance phase; Condylar motion; Fluoroscopy; Femoral rollback ID CRUCIATE LIGAMENT DEFICIENCY; WEIGHT-BEARING ACTIVITIES; KNEE-JOINT MOTION; TREADMILL WALKING; CONTACT KINEMATICS; MUSCLE ACTIVATION; REACTION FORCE; ACL-DEFICIENT; LEVEL WALKING; VIVO MOTION AB Accurate knowledge of the dynamic knee motion in-vivo is instrumental for understanding normal and pathological function of the knee joint. However, interpreting motion of the knee joint during gait in other than the sagittal plane remains controversial. In this study, we utilized the dual fluoroscopic imaging technique to investigate the six-degree-of-freedom kinematics and condylar motion of the knee during the stance phase of treadmill gait in eight healthy volunteers at a speed of 0.67 m/s. We hypothesized that the 6DOF knee kinematics measured during gait will be different from those reported for non-weightbearing activities, especially with regards to the phenomenon of femoral rollback. In addition, we hypothesized that motion of the medial femoral condyle in the transverse plane is greater than that of the lateral femoral condyle during the stance phase of treadmill gait. The rotational motion and the anterior-posterior translation of the femur with respect to the tibia showed a clear relationship with the flexion-extension path of the knee during the stance phase. Additionally, we observed that the phenomenon of femoral rollback was reversed, with the femur noted to move posteriorly with extension and anteriorly with flexion. Furthermore, we noted that motion of the medial femoral condyle in the transverse plane was greater than that of the lateral femoral condyle during the stance phase of gait (17.4 +/- 2.0 mm vs. 7.4 +/- 6.1 mm, respectively; p < 0.01). The trend was opposite to what has been observed during non-weightbearing flexion or single-leg lunge in previous studies. These data provide baseline knowledge for the understanding of normal physiology and for the analysis of pathological function of the knee joint during walking. These findings further demonstrate that knee kinematics is activity-dependent and motion patterns of one activity (non-weightbearing flexion or lunge) cannot be generalized to interpret a different one (gait). (C) 2009 Elsevier Ltd. All rights reserved. C1 [Kozanek, Michal; Hosseini, Ali; Liu, Fang; Van de Velde, Samuel K.; Gill, Thomas J.; Rubash, Harry E.; Li, Guoan] Massachusetts Gen Hosp, Dept Pathol, Bioengn Lab, Boston, MA 02114 USA. [Kozanek, Michal; Hosseini, Ali; Liu, Fang; Van de Velde, Samuel K.; Gill, Thomas J.; Rubash, Harry E.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hosseini, Ali] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Pathol, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institute of Health [R01 AR 052408, R21 AR051078]; Department of Orthopaedic Surgery at Massachusetts General Hospital FX We would like to gratefully acknowledge the financial support of the National Institute of Health (R01 AR 052408, R21 AR051078) and the Department of Orthopaedic Surgery at Massachusetts General Hospital. We would also like to thank the volunteers who participated in this study and Bijoy Thomas, Gang Li, Hemanth Gadikota and Qun Xia for technical assistance. NR 48 TC 78 Z9 79 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD AUG 25 PY 2009 VL 42 IS 12 BP 1877 EP 1884 DI 10.1016/j.jbiomech.2009.05.003 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 493KB UT WOS:000269734200010 PM 19497573 ER PT J AU Block, K Gorin, Y Abboud, HE AF Block, Karen Gorin, Yves Abboud, Hanna E. TI Subcellular localization of Nox4 and regulation in diabetes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE kidney; mitochondria; oxidative stress ID NADPH OXIDASE; NAD(P)H OXIDASE; ENDOTHELIAL-CELLS; MESANGIAL CELLS; MITOCHONDRIA; EXPRESSION; SUPEROXIDE; IDENTIFICATION; NEPHROPATHY; APOPTOSIS AB Oxidative stress is implicated in human diseases. Some of the oxidative pathways are harbored in the mitochondria. NAD(P) H oxidases have been identified not only in phagocytic but also in somatic cells. Nox4 is the most ubiquitous of these oxidases and is a major source of reactive oxygen species (ROS) in many cell types and in kidney tissue of diabetic animals. We generated specific Nox4 antibodies, and found that Nox4 localizes to mitochondria. (i) Immunoblot analysis in cultured mesangial cells and kidney cortex revealed that Nox4 is present in crude mitochondria, in mitochondria-enriched heavy fractions, and in purified mitochondria; (ii) immunofluorescence confocal microscopy also revealed that Nox4 localizes with the mitochondrial marker Mitotracker; and (iii) the mitochondrial localization prediction program MitoProt indicated that the probability score for Nox4 is identical to mitochondrial protein cytochrome c oxidase subunit IV. We also show that in purified mitochondria, siRNA-mediated knockdown of Nox4 significantly reduces NADPH oxidase activity in pure mitochondria and blocks glucose-induced mitochondrial superoxide generation. In a rat model of diabetes, mitochondrial Nox4 expression is increased in kidney cortex. Our data provide evidence that a functional Nox4 is present and regulated in mitochondria, indicating the existence of a previously undescribed source of ROS in this organelle. C1 [Block, Karen; Gorin, Yves; Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Abboud, Hanna E.] S Texas Vet Hlth Care Syst, Audie Leon Murphy Mem Hosp Div, San Antonio, TX 78229 USA. RP Abboud, HE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM abboud@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925 FU Juvenile Diabetes Research Foundation; South Central Affiliate of the American Heart Association; American Diabetes Association; National Institutes of Health [076923, R01 CA 131272, DK 43988, DK 33665]; National Institute of Diabetes and Digestive and Kidney Diseases-National Institutes of Health George O'Brien Kidney Research Center; Veterans Administration FX We thank D.-Y. Lee and P. Hoover for technical contributions, and J. Barnes for electron microscopy and rabbit immunization. This work was supported by grants from the Juvenile Diabetes Research Foundation Regular research (Y.G. and H.E.A.); a grant-in-aid from the South Central Affiliate of the American Heart Association (Y.G.); the American Diabetes Association (H.E.A.); the National Institutes of Health K01 Award DK 076923 and Grant R01 CA 131272 (K.B.); National Institutes of Health Grants DK 43988 and DK 33665 (H.E.A.); the National Institute of Diabetes and Digestive and Kidney Diseases-National Institutes of Health George O'Brien Kidney Research Center (H.E.A. and Y.G.); and the Veterans Administration (H.E.A. and K.B.). NR 32 TC 195 Z9 195 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2009 VL 106 IS 34 BP 14385 EP 14390 DI 10.1073/pnas.0906805106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487SF UT WOS:000269295100041 PM 19706525 ER PT J AU Borowiec, M Liew, CW Thompson, R Boonyasrisawat, W Hu, J Mlynarski, WM El Khattabi, I Kim, SH Marselli, L Rich, SS Krolewski, AS Bonner-Weir, S Sharma, A Sale, M Mychaleckyj, JC Kulkarni, RN Doria, A AF Borowiec, Maciej Liew, Chong W. Thompson, Ryan Boonyasrisawat, Watip Hu, Jiang Mlynarski, Wojciech M. El Khattabi, Ilham Kim, Sung-Hoon Marselli, Lorella Rich, Stephen S. Krolewski, Andrzej S. Bonner-Weir, Susan Sharma, Arun Sale, Michele Mychaleckyj, Josyf C. Kulkarni, Rohit N. Doria, Alessandro TI Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE beta cells; genetics; MODY; tyrosine kinase ID INSULIN-SECRETION; ALPHA-GENE; EXPRESSION; MELLITUS; ASSOCIATION; MODIFIERS; VARIANTS; CARRIERS; NKX6.1; MODY3 AB Maturity-onset diabetes of the young (MODY) is a subtype of diabetes defined by an autosomal pattern of inheritance and a young age at onset, often before age 25. MODY is genetically heterogeneous, with 8 distinct MODY genes identified to date and more believed to exist. We resequenced 732 kb of genomic sequence at 8p23 in 6 MODY families unlinked to known MODY genes that showed evidence of linkage at that location. Of the 410 sequence differences that we identified, 5 had a frequency <1% in the general population and segregated with diabetes in 3 of the families, including the 2 showing the strongest support for linkage at this location. The 5 mutations were all placed within 100 kb corresponding to the BLK gene. One resulted in an Ala71Thr substitution; the other 4 were noncoding and determined decreased in vitro promoter activity in reporter gene experiments. We found that BLK-a nonreceptor tyrosine-kinase of the src family of proto-oncogenes-is expressed in beta-cells where it enhances insulin synthesis and secretion in response to glucose by up-regulating transcription factors Pdx1 and Nkx6.1. These actions are greatly attenuated by the Ala71Thr mutation. These findings point to BLK as a previously unrecognized modulator of beta-cell function, the deficit of which may lead to the development of diabetes. C1 [Doria, Alessandro] Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Sect Genet & Epidemiol, Boston, MA 02215 USA. [Borowiec, Maciej; Liew, Chong W.; Boonyasrisawat, Watip; El Khattabi, Ilham; Kim, Sung-Hoon; Marselli, Lorella; Krolewski, Andrzej S.; Bonner-Weir, Susan; Sharma, Arun; Kulkarni, Rohit N.; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Borowiec, Maciej; Mlynarski, Wojciech M.] Med Univ Lodz, Dept Pediat, PL-91738 Lodz, Poland. [Rich, Stephen S.; Sale, Michele; Mychaleckyj, Josyf C.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. RP Doria, A (reprint author), Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu RI Borowiec, Maciej/S-9220-2016 FU National Institutes of Health [DK55523, DK 67536, DK36836]; American Diabetes Association; Iacocca Fellowship Award FX This work was supported by National Institutes of Health Grants DK55523 (to A. D.), DK 67536 (to R. N. K.), and DK36836 (Genetics Core, Specialized Assay Core, and Advanced Microscopy Core of the Diabetes and Endocrinology Research Center at the Joslin Diabetes Center). M. B. and S. H. K. were supported by a Mentor-based Postdoctoral Fellowship from the American Diabetes Association. C. L. W. was the recipient of an Iacocca Fellowship Award. NR 27 TC 53 Z9 56 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2009 VL 106 IS 34 BP 14460 EP 14465 DI 10.1073/pnas.0906474106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487SF UT WOS:000269295100054 PM 19667185 ER PT J AU Barrington, RA Schneider, TJ Pitcher, LA Mempel, TR Ma, MH Barteneva, NS Carroll, MC AF Barrington, Robert A. Schneider, Thomas J. Pitcher, Lisa A. Mempel, Thorsten R. Ma, Minghe Barteneva, Natasha S. Carroll, Michael C. TI Uncoupling CD21 and CD19 of the B-cell coreceptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE B-cell memory; complement receptors; germinal centers; humoral immunity ID FOLLICULAR DENDRITIC CELLS; HUMORAL IMMUNE-RESPONSE; COMPLEMENT RECEPTORS 1; T-DEPENDENT ANTIGEN; GERMINAL CENTER; ANTIBODY-RESPONSES; AUTOIMMUNE-DISEASE; CD19/CD21 COMPLEX; TRANSGENIC MICE; LIPID RAFTS AB Complement receptors (CRs) CD21 and CD35 form a coreceptor with CD19 and CD81 on murine B cells that when coligated with the B-cell receptor lowers the threshold of activation by several orders of magnitude. This intrinsic signaling role is thought to explain the impaired humoral immunity of mice bearing deficiency in CRs. However, CRs have additional roles on B cells independent of CD19, such as transport of C3-coated immune complexes and regulation of C4 and C3 convertase. To test whether association of CR with CD19 is necessary for their intrinsic activation-enhancing role, knockin mice expressing mutant receptors, Cr2(Delta/Delta gfp), that bind C3 ligands but do not signal through CD19 were constructed. We found that uncoupling of CR and CD19 significantly diminishes survival of germinal center B cells and secondary antibody titers. However, B memory is less impaired relative to mice bearing a complete deficiency in CRs on B cells. These findings confirm the importance of interaction of CR and CD19 for coreceptor activity in humoral immunity but identify a role for CR in B-cell memory independent of CD19. C1 [Barteneva, Natasha S.; Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Barrington, Robert A.; Schneider, Thomas J.; Pitcher, Lisa A.; Ma, Minghe; Barteneva, Natasha S.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Mempel, Thorsten R.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM carroll@idi.harvard.edu FU National Institutes of Health [AI39246, AI40181, 1 F32 AR08644, 2 T32 HL066987] FX We thank Svend Rietdij for help on the Ca2+ flux assay, Franziska Schuerpf for assistance with confocal microscopy, and Young-AKimfor assistance with the preparation and analysis of uptake of ICs. Wethank Dr. David Karp for providing C3d-biotin and Dr. David Isenman (University of Toronto, Toronto, ON, Canada) for purified human C3d. This work was supported by National Institutes of Health Grants AI39246 and AI40181 (to M. C. C.); 1 F32 AR08644 (to T. J. S.); and 2 T32 HL066987 (to R. A. B. and L. A. P.). NR 57 TC 18 Z9 18 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2009 VL 106 IS 34 BP 14490 EP 14495 DI 10.1073/pnas.0903477106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487SF UT WOS:000269295100059 PM 19706534 ER PT J AU Coser, KR Wittner, BS Rosenthal, NF Collins, SC Melas, A Smith, SL Mahoney, CJ Shioda, K Isselbacher, KJ Ramaswamy, S Shioda, T AF Coser, Kathryn R. Wittner, Ben S. Rosenthal, Noel F. Collins, Sabrina C. Melas, Antonia Smith, Shannon L. Mahoney, Crystal J. Shioda, Keiko Isselbacher, Kurt J. Ramaswamy, Sridhar Shioda, Toshi TI Antiestrogen-resistant subclones of MCF-7 human breast cancer cells are derived from a common monoclonal drug-resistant progenitor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE acquired resistance; clonal selection; DNA copy number; fulvestrant; tumor heterogeneity ID EXPRESSION; ESTROGEN; SIGNATURE; APOPTOSIS; ABERRATIONS; METASTASIS; INDUCTION; EVOLUTION; RECEPTOR; THERAPY AB Emergence of antiestrogen-resistant cells in MCF-7 cells during suppression of estrogen signaling is a widely accepted model of acquired breast cancer resistance to endocrine therapy. To obtain insight into the genomic basis of endocrine therapy resistance, we characterized MCF-7 monoclonal sublines that survived 21-day exposure to tamoxifen (T-series sublines) or fulvestrant (F-series sublines) and sublines unselected by drugs (U-series). All T/F-sublines were resistant to the cytocidal effects of both tamoxifen and fulvestrant. However, their responses to the cytostatic effects of fulvestrant varied greatly, and their remarkably diversified morphology showed no correlation with drug resistance. mRNA expression profiles of the U-sublines differed significantly from those of the T/F-sublines, whose transcriptomal responsiveness to fulvestrant was largely lost. A set of genes strongly expressed in the U-sublines successfully predicted metastasis-free survival of breast cancer patients. Most T/F-sublines shared highly homogeneous genomic DNA aberration patterns that were distinct from those of the U-sublines. Genomic DNA of the U-sublines harbored many aberrations that were not found in the T/F-sublines. These results suggest that the T/F-sublines are derived from a common monoclonal progenitor that lost transcriptomal responsiveness to antiestrogens as a consequence of genetic abnormalities many population doublings ago, not from the antiestrogen-sensitive cells in the same culture during the exposure to antiestrogens. Thus, the apparent acquisition of antiestrogen resistance by MCF-7 cells reflects selection of preexisting drug-resistant subpopulations without involving changes in individual cells. Our results suggest the importance of clonal selection in endocrine therapy resistance of breast cancer. C1 [Coser, Kathryn R.; Wittner, Ben S.; Rosenthal, Noel F.; Collins, Sabrina C.; Melas, Antonia; Smith, Shannon L.; Mahoney, Crystal J.; Shioda, Keiko; Isselbacher, Kurt J.; Ramaswamy, Sridhar; Shioda, Toshi] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA 02129 USA. [Coser, Kathryn R.; Wittner, Ben S.; Rosenthal, Noel F.; Collins, Sabrina C.; Melas, Antonia; Smith, Shannon L.; Mahoney, Crystal J.; Shioda, Keiko; Isselbacher, Kurt J.; Ramaswamy, Sridhar; Shioda, Toshi] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Wittner, Ben S.; Ramaswamy, Sridhar] Broad Inst, Cambridge, MA 02142 USA. [Wittner, Ben S.; Ramaswamy, Sridhar] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Isselbacher, KJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA 02129 USA. EM isselbacher@helix.mgh.harvard.edu; tshioda@partners.org FU Susan G. Komen for Cure [FAS0703860, KG090515]; AVONBreast Cancer Crusade Fund(AVONFoundation); AstraZeneca Development Compound Research Fund; National Cancer Institute Breast Cancer Specialized Program of Research Excellence Award [2P50 CA89393-07]; Department of Defense Center of Excellence in Breast Cancer Award [BC05-COE W81XH-06-2-0033] FX We thank Ana Soto and Carlos Sonnenschein (Tufts University) for MCF-7 BUS cell culture, Ai Muto (Kyoto University) for bioinformatics, and Haley Ellis for technical support. We also thank Steven Isakoff, Paul Goss, and Jeff Settleman for useful discussions. This study was supported by Grants FAS0703860 and KG090515 from Susan G. Komen for Cure, from the AVONBreast Cancer Crusade Fund(AVONFoundation), and from AstraZeneca Development Compound Research Fund (to T. S). S. R. and B. S. W. were supported by National Cancer Institute Breast Cancer Specialized Program of Research Excellence Award 2P50 CA89393-07 to the Dana-Farber/Harvard Cancer Center and a Department of Defense Center of Excellence in Breast Cancer Award BC05-COE W81XH-06-2-0033. NR 24 TC 35 Z9 38 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2009 VL 106 IS 34 BP 14536 EP 14541 DI 10.1073/pnas.0907560106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487SF UT WOS:000269295100067 PM 19706540 ER PT J AU Ren, DC Kim, H Tu, HC Westergard, TD Fisher, JK Rubens, JA Korsmeyer, SJ Hsieh, JJD Cheng, EHY AF Ren, Decheng Kim, Hyungjin Tu, Ho-Chou Westergard, Todd D. Fisher, Jill K. Rubens, Jeff A. Korsmeyer, Stanley J. Hsieh, James J. -D. Cheng, Emily H. -Y. TI The VDAC2-BAK Rheostat Controls Thymocyte Survival SO SCIENCE SIGNALING LA English DT Article ID MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; DEPENDENT ANION CHANNELS; BCL-2 FAMILY-MEMBERS; CELL-DEATH; BH3-ONLY PROTEINS; OLIGOMERIZES BAK; TRANSITION PORE; CYTOCHROME-C; BH3 DOMAINS; APOPTOSIS AB The proapoptotic proteins BAX and BAK constitute the mitochondrial apoptotic gateway that executes cellular demise after integrating death signals. The lethal BAK is kept in check by voltage-dependent anion channel 2 (VDAC2), a mammalian-restricted VDAC isoform. Here, we provide evidence showing a critical role for the VADC2-BAK complex in determining thymocyte survival in vivo. Genetic depletion of Vdac2 in the thymus resulted in excessive cell death and hypersensitivity to diverse death stimuli including engagement of the T cell receptor. These phenotypes were completely rescued by the concurrent deletion of Bak but not that of Bax. Thus, the VDAC2-BAK axis provides a mechanism that governs the homeostasis of thymocytes. Our study reveals a sophisticated built-in rheostat that likely fine-tunes immune competence to balance autoimmunity and immunodeficiency. C1 [Ren, Decheng; Kim, Hyungjin; Tu, Ho-Chou; Westergard, Todd D.; Hsieh, James J. -D.; Cheng, Emily H. -Y.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Fisher, Jill K.; Rubens, Jeff A.; Korsmeyer, Stanley J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cheng, Emily H. -Y.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA. RP Cheng, EHY (reprint author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. EM echeng@dom.wustl.edu RI Ren, decheng/B-8310-2011 FU NCI NIH HHS [R01 CA125562, K01 CA098320] NR 35 TC 28 Z9 29 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD AUG 25 PY 2009 VL 2 IS 85 AR ra48 DI 10.1126/scisignal.2000274 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 569MW UT WOS:000275602200004 PM 19706873 ER PT J AU Tien, PC Schneider, MF Cole, SR Cohen, MH Glesby, MJ Lazar, J Young, M Mack, W Hodis, HN Kaplan, RC AF Tien, Phyllis C. Schneider, Michael F. Cole, Stephen R. Cohen, Mardge H. Glesby, Marshall J. Lazar, Jason Young, Mary Mack, Wendy Hodis, Howard N. Kaplan, Robert C. TI Association of hepatitis C virus and HIV infection with subclinical atherosclerosis in the women's interagency HIV study SO AIDS LA English DT Article ID INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; CAROTID-ARTERY; RISK-FACTORS; INDIVIDUALS; PROGRESSION AB Whether hepatitis C virus coinfection might accelerate atherosclerosis in HIV-infected individuals is unclear. We examined the relationship of HIV and hepatitis C virus with carotid artery intima media thickness and the presence of carotid plaques in the Women's Interagency HIV Study. Hepatitis C virus infection was not associated with greater carotid artery intima media thickness after adjustment for demographic and traditional cardiovascular risk factors. Further follow-up is needed to clarify whether HIV/hepatitis C virus coinfection may be associated with a greater risk of carotid plaque. C1 [Tien, Phyllis C.] Univ Calif San Francisco, VAMC, Infect Dis Sect, Dept Med, San Francisco, CA 94121 USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Schneider, Michael F.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Cole, Stephen R.] Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Cohen, Mardge H.] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA. [Glesby, Marshall J.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Lazar, Jason] SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA. [Young, Mary] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Mack, Wendy] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Hodis, Howard N.] Univ So Calif, Atherosclerosis Res Unit, Los Angeles, CA USA. [Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Tien, PC (reprint author), Univ Calif San Francisco, VAMC, Infect Dis Sect, Dept Med, 111W,4150 Clement St, San Francisco, CA 94121 USA. EM ptien@ucsf.edu RI Kaplan, Robert/A-2526-2011 FU National Institute of Allergy Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UOI-AI-34993, UOI-AI-42590]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute Oil Deafness and Other Communication Disorders; National Institute of Allergy and Infectious Diseases [R01-AI-052065, R01-AI-0577006, K23 AI 66943, K24 AI 078884] FX Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gauge). The WIHS is funded by the National Institute of Allergy Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UOI-AI-34993, and UOI-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632). The study is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute Oil Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). HCV testing was supported by grants from the National Institute of Allergy and Infectious Diseases (R01-AI-052065 and R01-AI-0577006). Dr P.C. Tien and Dr M.J. Glesby are supported by the National Institute of Allergy and Infectious Diseases through K23 AI 66943 and K24 AI 078884, respectively. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 20 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD AUG 24 PY 2009 VL 23 IS 13 BP 1781 EP 1784 DI 10.1097/QAD.0b013e32832d7aa8 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 488FF UT WOS:000269333900019 PM 19553807 ER PT J AU Zhu, AX AF Zhu, Andrew X. TI Predicting the response to sorafenib in hepatocellular carcinoma: where is the evidence for phosphorylated extracellular signaling-regulated kinase (pERK)? SO BMC MEDICINE LA English DT Editorial Material ID RAF/MEK/ERK PATHWAY; TUMOR PROGRESSION; OVER-EXPRESSION; ERK; ANGIOGENESIS; APOPTOSIS; TARGETS; CANCER; RAF AB The approval of sorafenib and active development of many other molecularly targeted agents in hepatocellular carcinoma (HCC) have presented a challenge to understand the mechanism of action of sorafenib and identify predictive biomarkers to select patients more likely to benefit from sorafenib. The preclinical study by Zhang and celleagues published this month in BMC Medicine provides preliminary evidence that baseline phosphorylated extracellular signaling-regulated kinase (pERK) may be a relevant marker to reflect the level of constitutive activation of the RAF/mitogen-activated protein kinase kinase (MEK)/ERK signaling pathway and has the potential value in predicting response to sorafenib. The clinical data from the initial single arm phase II study and preliminary report from the randomized phase III study also suggest the correlation of baseline archived tumor pERK levels and time to tumor progression in HCC patients. Whether baseline pERK will prove to be a useful predictive biomarker of response and clinical benefits for sorafenib in HCC will need to be validated in future large prospective studies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02115 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02115 USA. EM azhu@partners.org NR 18 TC 6 Z9 6 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD AUG 24 PY 2009 VL 7 AR 42 DI 10.1186/1741-7015-7-42 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 502TR UT WOS:000270483600002 PM 19703270 ER PT J AU Xiong, JP Mahalingham, B Alonso, JL Borrelli, LA Rui, XL Anand, S Hyman, BT Rysiok, T Muller-Pompalla, D Goodman, SL Arnaout, MA AF Xiong, Jian-Ping Mahalingham, Bhuvaneshwari Alonso, Jose Luis Borrelli, Laura Ann Rui, Xianliang Anand, Saurabh Hyman, Bradley T. Rysiok, Thomas Mueller-Pompalla, Dirk Goodman, Simon L. Arnaout, M. Amin TI Crystal structure of the complete integrin alpha V beta 3 ectodomain plus an alpha/beta. transmembrane fragment SO JOURNAL OF CELL BIOLOGY LA English DT Article; Proceedings Paper CT Gordon Research Conference on Fibronectin, Integrins and Related Molecules CY FEB 01-06, 2009 CL Ventura, CA ID LIFETIME IMAGING MICROSCOPY; REAL-TIME ANALYSIS; LIGAND-BINDING; A-DOMAIN; CONFORMATIONAL REGULATION; EXTRACELLULAR SEGMENT; HUMAN-MELANOMA; ACTIVATION; FIBRONECTIN; FRET AB We determined the crystal structure of 1TM-alpha V beta 3, which represents the complete unconstrained ectodomain plus short C-terminal transmembrane stretches of the alpha V and beta 3 subunits. 1TM-alpha V beta 3 is more compact and less active in solution when compared with Delta TM-alpha V beta 3, which lacks the short C-terminal stretches. The structure reveals a bent conformation and defines the alpha-beta interface between IE2 (EGF-like 2) and the thigh domains. Modifying this interface by site-directed mutagenesis leads to robust integrin activation. Fluorescent life-time imaging microscopy of inactive full-length alpha V beta 3 on live cells yields a donor-membrane acceptor distance, which is consistent with the bent conformation and does not change in the activated integrin. These data are the first direct demonstration of conformational coupling of the integrin leg and head domains, identify the IE2-thigh interface as a critical steric barrier in integrin activation, and suggest that inside-out activation in intact cells may involve conformational changes other than the postulated switch to a genu-linear state. C1 [Xiong, Jian-Ping; Mahalingham, Bhuvaneshwari; Alonso, Jose Luis; Rui, Xianliang; Anand, Saurabh; Arnaout, M. Amin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Leukocyte Biol & Inflammat, Charlestown, MA 02129 USA. [Xiong, Jian-Ping; Mahalingham, Bhuvaneshwari; Alonso, Jose Luis; Rui, Xianliang; Anand, Saurabh; Arnaout, M. Amin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Struct Biol,Nephrol Div,Dept Med, Charlestown, MA 02129 USA. [Borrelli, Laura Ann; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Rysiok, Thomas] Merck Serono Res, Biol Prot & Cell Sci, D-64293 Darmstadt, Germany. [Mueller-Pompalla, Dirk] Merck Serono Res, Biol Prot Purificat, D-64293 Darmstadt, Germany. [Goodman, Simon L.] Merck Serono Res, Therapeut Area Oncol Biochem & Cellular Pharmacol, D-64293 Darmstadt, Germany. RP Arnaout, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Leukocyte Biol & Inflammat, Charlestown, MA 02129 USA. EM arnaout@receptor.mgh.harvard.edu RI Alonso, Jose Luis/G-7961-2012 FU NHLBI NIH HHS [HL070219, R01 HL070219]; NIDDK NIH HHS [DK07447] NR 56 TC 81 Z9 85 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG 24 PY 2009 VL 186 IS 4 BP 589 EP 600 DI 10.1083/jcb.200905085 PG 12 WC Cell Biology SC Cell Biology GA 489RH UT WOS:000269439200014 PM 19704023 ER PT J AU Hook, VYH Kindy, M Reinheckel, T Peters, C Hook, G AF Hook, Vivian Y. H. Kindy, Mark Reinheckel, Thomas Peters, Christoph Hook, Gregory TI Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Beta-amyloid; Cathepsin B; Gene knockout; Amyloid precursor protein; Protease ID REGULATED SECRETORY VESICLES; ALZHEIMERS-DISEASE; IN-VIVO; CHROMAFFIN CELLS; GUINEA-PIGS; INHIBITORS; BACE; PATHWAYS; SEQUENCE; THERAPY AB Neurotoxic beta-amyloid (A beta) peptides participate in Alzheimer's disease (AD); therefore, reduction of A beta generated from APP may provide a therapeutic approach for AD. Gene knockout studies in transgenic mice producing human A beta may identify targets for reducing A beta. This study shows that knockout of the cathepsin B gene in mice expressing human wild-type APP (hAPPwt) results in substantial decreases in brain A beta 40 and A beta 42 by 67% and decreases in levels of the C-terminal beta-secretase fragment (CTF beta) derived from APP. In contrast, knockout of cathepsin B in mice expressing hAPP with the rare Swedish (Swe) and Indiana (Ind) mutations had no effect on A beta. The difference in reduction of A beta in hAPPwt mice, but not in hAPPSwe/Ind mice, shows that the transgenic model can affect cathepsin B gene knockout results. Since most AD patients express hAPPwt, these data validate cathepsin B as a target for development of inhibitors to lower A beta in AD. (C) 2009 Elsevier Inc. All rights reserved. C1 [Hook, Vivian Y. H.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Neurosci, La Jolla, CA 92093 USA. [Hook, Vivian Y. H.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Med & Pharmacol, La Jolla, CA 92093 USA. [Kindy, Mark] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Neurosci, Charleston, SC 29425 USA. [Reinheckel, Thomas; Peters, Christoph] Univ Freiburg, Zentrum Biochem & Mol Zellforsch, Inst Mol Med & Zellforsch, D-79104 Freiburg, Germany. [Hook, Gregory] Amer Life Sci Pharmaceut Inc, San Diego, CA 92109 USA. RP Hook, VYH (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Neurosci, 9500 Gilman Dr,MC 0744, La Jolla, CA 92093 USA. EM vhook@ucsd.edu FU NIA/NIH [R21 AG027446, 1R44AG032784] FX We thank Dr. M.D. Pierschbacher for helpful review of the manuscript. This research was supported by the NIA/NIH R21 Grant AG027446 and 1R44AG032784 (to American Life Science Pharmaceuticals (ALSP)). V.H. holds equity in ALSP and serves on the Scientific Advisory Board of ALSP. The terms of this agreement have been reviewed by the University of California, San Diego, in accordance with its conflict of interest policies. G.H. holds equity in and is employed by ALSP. NR 32 TC 35 Z9 35 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 21 PY 2009 VL 386 IS 2 BP 284 EP 288 DI 10.1016/j.bbrc.2009.05.131 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 470FH UT WOS:000267960100003 PM 19501042 ER PT J AU Kajiya, M Sato, K Silva, MJB Ouhara, K Do, PM Shanmugam, KT Kawai, T AF Kajiya, Mikihito Sato, Kimihiro Silva, Marcelo J. B. Ouhara, Kazuhisa Do, Phi M. Shanmugam, K. T. Kawai, Toshihisa TI Hydrogen from intestinal bacteria is protective for Concanavalin A-induced hepatitis SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Hepatitis; Concanavalin A; Molecular hydrogen; Inflammation; Mouse model; Lymphocytes; Bacteria; Antibiotics; TNF-alpha; IFN-gamma ID ESCHERICHIA-COLI; OXIDATIVE STRESS; LIVER-INJURY; FAS LIGAND; TNF-ALPHA; MICE; INHALATION; INVOLVEMENT; METABOLISM; GENE AB It is well known that some intestinal bacteria, such as Escherichia coli, can produce a remarkable amount of molecular hydrogen (H(2)). Although the antioxidant effects of H(2) are well documented, the present study examined whether H(2) released from intestinally colonized bacteria could affect Concanavalin A (ConA)-induced mouse hepatitis. Systemic antibiotics significantly decreased the level of H(2) in both liver and intestines along with suppression of intestinal bacteria. As determined by the levels of AST, ALT, TNF-alpha and IFN-gamma in serum, suppression of intestinal bacterial flora by antibiotics increased the severity of ConA-induced hepatitis, while reconstitution of intestinal flora with H(2)-producing E. coli, but not H(2)-deficient mutant E. coli, down-regulated the ConA-induced liver inflammation. Furthermore, in vitro production of both TNF-alpha and IFN-gamma by ConA-stimulated spleen lymphocytes was significantly inhibited by the introduction of H(2). These results indicate that H(2) released from intestinal bacteria can suppress inflammation induced in liver by ConA. (C) 2009 Elsevier Inc. All rights reserved. C1 [Kajiya, Mikihito; Silva, Marcelo J. B.; Ouhara, Kazuhisa; Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Boston, MA USA. [Sato, Kimihiro] Skyview Enterprises, New York, NY USA. [Do, Phi M.; Shanmugam, K. T.] Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA USA. EM tkawai@forsyth.org OI Silva, Marcelo/0000-0002-5807-4286 FU Skyview Enterprises FX This study was supported by a research grant from Skyview Enterprises. NR 23 TC 48 Z9 54 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 21 PY 2009 VL 386 IS 2 BP 316 EP 321 DI 10.1016/j.bbrc.2009.06.024 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 470FH UT WOS:000267960100009 PM 19523450 ER PT J AU Tzatsos, A AF Tzatsos, Alexandros TI Raptor Binds the SAIN (Shc and IRS-1 NPXY Binding) Domain of Insulin Receptor Substrate-1 (IRS-1) and Regulates the Phosphorylation of IRS-1 at Ser-636/639 by mTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMALIAN TARGET; DEPENDENT PHOSPHORYLATION; SERINE PHOSPHORYLATION; PROTEIN-KINASE; S6 KINASE; TOS MOTIF; RAPAMYCIN; PATHWAY; AKT/PKB; DEGRADATION AB In normal physiological states mTOR phosphorylates and activates Akt. However, under diabetic-mimicking conditions mTOR inhibits phosphatidylinositol (PI) 3-kinase/Akt signaling by phosphorylating insulin receptor substrate-1 (IRS-1) at Ser-636/639. The molecular basis for the differential effect of mTOR signaling on Akt is poorly understood. Here, it has been shown that knockdown of mTOR, Raptor, and mLST8, but not Rictor and mSin1, suppresses insulin-stimulated phosphorylation of IRS-1 at Ser-636/639 and stabilizes IRS-1 after long term insulin stimulation. This phosphorylation depends on the PI 3-kinase/PDK1 axis but is Akt-independent. At the molecular level, Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of IRS-1 and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR. IRS-1 lacking the SAIN domain does not interact with Raptor, is not phosphorylated at Ser-636/639, and favorably interacts with PI 3-kinase. Overall, these data provide new insights in the molecular mechanisms by which mTORC1 inhibits PI 3-kinase/Akt signaling at the level of IRS-1 and suggest that mTOR signaling toward Akt is scaffold-dependent. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Tzatsos, A (reprint author), Massachusetts Gen Hosp, Ctr Canc, Simches Res Bldg,CPZN 4100,185 Cambridge St, Boston, MA 02114 USA. EM atzatsos@partners.org FU E. Nestora FX This work was supported by E. Nestora. NR 39 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 2009 VL 284 IS 34 BP 22525 EP 22534 DI 10.1074/jbc.M109.027748 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 483KG UT WOS:000268963100005 PM 19561084 ER PT J AU Bhaumik, J Weissleder, R McCarthy, JR AF Bhaumik, Jayeeta Weissleder, Ralph McCarthy, Jason R. TI Synthesis and Photophysical Properties of Sulfonamidophenyl Porphyrins as Models for Activatable Photosensitizers SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SELECTIVE FLUORESCENT-PROBE; PHOTODYNAMIC THERAPY; DISEASE; CANCER; HOMOCYSTEINE; PHOTOIMMUNOTHERAPY; PHOTOANGIOPLASTY; NANOPARTICLE; CONJUGATION; DELIVERY AB The ability to localize agents to specific anatomic sites remains an important aspect in designing more efficient therapeutics. Light-activated therapies, in particular. allow for the focal ablation of target tissues and cells, In order to increase the specificity of these agents, stimuli-activated systems have been developed, which are nonphototoxic in the absence of activation. To this end, we propose a novel paradigm for excited state quenching and activation based upon the direct conjugation of quenching moieties to the porphyrinic macrocycle. Model compounds, based upon meso-(p-aminophenyl)porphyrins were synthesized bearing I to 4 sulfonamide-linked 2,4-dinitrobenzene. The singlet oxygen and fluorescence quantum yields of these compounds were obtained and compared, as well as the kinetics of activation with relevant activating agents. In addition. methods were developed to further modify the porphyrin in order to modulate the polarity and effect conjugation to biomolecules or nanoparticulate scaffolds. These systems may prove useful ill the treatment of a number of disease states, such as cancer and bacterial infection. C1 [McCarthy, Jason R.] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP McCarthy, JR (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 149 13th St,Room 5406, Charlestown, MA 02129 USA. EM jason_mccarthy@hms.harvard.edu FU NIH [U24-CA092782, U01-HL080731, U54-CA119349, U54-CA126515] FX We thank Dr. Scott A. Hilderbrand for his helpful discussions. This work was supported in part by NIH grants U24-CA092782(RW). U01-HL080731 (JM, RW), U54-CA119349(RW), and U54-CA126515 (RW). NMR data were obtained at the Department of Chemistry, University of Connecticut, with great thanks to Dr. Martha Morton. NR 31 TC 15 Z9 15 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD AUG 21 PY 2009 VL 74 IS 16 BP 5894 EP 5901 DI 10.1021/jo900832y PG 8 WC Chemistry, Organic SC Chemistry GA 482RV UT WOS:000268907300014 PM 19610602 ER PT J AU Athar, BS Paganetti, H AF Athar, Basit S. Paganetti, Harald TI Neutron equivalent doses and associated lifetime cancer incidence risks for head & neck and spinal proton therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIATION-THERAPY; POOLED ANALYSIS; 2ND CANCERS; IRRADIATION; ORGAN; MODEL; IMRT; PHANTOMS; TOOLKIT; AGE AB In this work we have simulated the absorbed equivalent doses to various organs distant to the field edge assuming proton therapy treatments of brain or spine lesions. We have used computational whole-body (gender-specific and age-dependent) voxel phantoms and considered six treatment fields with varying treatment volumes and depths. The maximum neutron equivalent dose to organs near the field edge was found to be approximately 8 mSv Gy(-1). We were able to clearly demonstrate that organ-specific neutron equivalent doses are age (stature) dependent. For example, assuming an 8-year-old patient, the dose to brain from the spinal fields ranged from 0.04 to 0.10 mSv Gy(-1), whereas the dose to the brain assuming a 9-month-old patient ranged from 0.5 to 1.0 mSv Gy(-1). Further, as the field aperture opening increases, the secondary neutron equivalent dose caused by the treatment head decreases, while the secondary neutron equivalent dose caused by the patient itself increases. To interpret the dosimetric data, we analyzed second cancer incidence risks for various organs as a function of patient age and field size based on two risk models. The results show that, for example, in an 8-year-old female patient treated with a spinal proton therapy field, breasts, lungs and rectum have the highest radiation-induced lifetime cancer incidence risks. These are estimated to be 0.71%, 1.05% and 0.60%, respectively. For an 11-year-old male patient treated with a spinal field, bronchi and rectum show the highest risks of 0.32% and 0.43%, respectively. Risks for male and female patients increase as their age at treatment time decreases. C1 [Athar, Basit S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Athar, BS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU Health Care Inc; Department of Radiation Oncology at Massachusetts General Hospital FX This work was supported by institutional funds (ECOR award by Partners Health Care Inc. and Ira Spiro award for translational research by the Department of Radiation Oncology at Massachusetts General Hospital (MGH)). NR 34 TC 26 Z9 26 U1 2 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG 21 PY 2009 VL 54 IS 16 BP 4907 EP 4926 DI 10.1088/0031-9155/54/16/005 PG 20 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 479MW UT WOS:000268664600005 PM 19641238 ER PT J AU Recht, A Ancukiewicz, M El-Din, MAA Lu, XQ Martin, C Berman, SM Hirsch, AE Kachnic, LA Katz, A MacDonald, S Nedea, EA Stevenson, MA Powell, SN Taghian, AG AF Recht, Abram Ancukiewicz, Marek El-Din, Mohamed A. Alm Lu, Xing-Qi Martin, Chrystalla Berman, Stuart M. Hirsch, Ariel E. Kachnic, Lisa A. Katz, Angela MacDonald, Shannon Nedea, Elena A. Stevenson, Mary Ann Powell, Simon N. Taghian, Alphonse G. TI Lung Dose-Volume Parameters and the Risk of Pneumonitis for Patients Treated With Accelerated Partial-Breast Irradiation Using Three-Dimensional Conformal Radiotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol ID INTENSITY-MODULATED RADIOTHERAPY; INITIAL DOSIMETRIC EXPERIENCE; RADIATION-THERAPY; CONSERVING THERAPY; PULMONARY COMPLICATIONS; RANDOMIZED-TRIAL; PROTON-BEAMS; CANCER; SURGERY; LUMPECTOMY AB Purpose There are no data on how complication rates after accelerated partial-breast irradiation delivered by three-dimensional conformal radiotherapy are affected by treatment technique. We therefore examined the risk of pneumonitis in relation to lung dose-volume parameters. Patients and Methods Our prospective dose-escalation trial enrolled 198 treated patients from 2003 to 2007. Patients received 32 or 36 Gy in 4-Gy fractions, given twice daily: 29 (14%) were treated with pure photons; 149 (77%) with mixed photons and electrons; and 20 (10%) with protons. Results There were four cases of pneumonitis at 4, 4, 7, and 9 months after treatment. All were in the 36-Gy cohort and were treated with pure photons. The risk of pneumonitis for the two cohorts combined was: 17% ( four of 24) for an ipsilateral lung volume (ILV) receiving 20 Gy or higher ( ILV, 20 Gy) of 3% or higher (P = .0002 for comparison to ILV 20 Gy < 3%, Fisher's exact test); 20% (four of 20) for an ILV 10 Gy of 10% or higher (P = .0001); and 15% (four of 26) for an ILV 5 Gy of 20% or higher (P = .0002). Conclusion The risk of pneumonitis appeared related to the ILV treated. This volume can be reduced by using mixed photons and electron when possible. We recommend that the ILV 20 Gy should be lower than 3%, the ILV 10 Gy lower than 10%, and the ILV 5 Gy lower than 20% when purely coplanar techniques are used. C1 [Recht, Abram] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Tanta Univ Hosp, Tanta Fac Med, Dept Radiat Oncol, Tanta, Egypt. RP Recht, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, East Campus,Finard Bldg B25,330 Brookline Ave, Boston, MA 02215 USA. EM arecht@bidmc.harvard.edu NR 36 TC 30 Z9 32 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2009 VL 27 IS 24 BP 3887 EP 3893 DI 10.1200/JCO.2008.20.0121 PG 7 WC Oncology SC Oncology GA 484RG UT WOS:000269064300005 PM 19620489 ER PT J AU Inskip, PD Robison, LL Stovall, M Smith, SA Hammond, S Mertens, AC Whitton, JA Diller, L Kenney, L Donaldson, SS Meadows, AT Neglia, JP AF Inskip, Peter D. Robison, Leslie L. Stovall, Marilyn Smith, Susan A. Hammond, Sue Mertens, Ann C. Whitton, John A. Diller, Lisa Kenney, Lisa Donaldson, Sarah S. Meadows, Anna T. Neglia, Joseph P. TI Radiation Dose and Breast Cancer Risk in the Childhood Cancer Survivor Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HODGKINS-DISEASE; YOUNG-WOMEN; 2ND MALIGNANCY; NEOPLASMS; CHEMOTHERAPY; RADIOTHERAPY; ADOLESCENCE; COHORT AB Purpose The purpose of this study was to quantify the risk of breast cancer in relation to radiation dose and chemotherapy among survivors of childhood cancer. Methods We conducted a case-control study of breast cancer in a cohort of 6,647 women who were 5-year survivors of childhood cancer and who were treated during 1970 through 1986. One hundred twenty patients with histologically confirmed breast cancer were identified and were individually matched to four selected controls on age at initial cancer and time since initial cancer. Medical physicists estimated radiation dose to the breast tumor site and ovaries on the basis of medical records. Results The odds ratio for breast cancer increased linearly with radiation dose, and it reached 11-fold for local breast doses of approximately 40 Gy relative to no radiation (P for trend < .0001). Risk associated with breast irradiation was sharply reduced among women who received 5 Gy or more to the ovaries (P = .002). The excess odds ratio per Gy was 0.36 for those who received ovarian doses less than 5 Gy and was 0.06 for those who received higher doses. Radiation-related risk did not vary significantly by age at exposure. Borderline significantly elevated risks were seen for doxorubicin, dactinomycin, dacarbazine, and carmustine. Conclusion Results confirm the radiation sensitivity of the breast in girls age 10 to 20 years but do not demonstrate a strong effect of age at exposure within this range. Irradiation of the ovaries at doses greater than 5 Gy seems to lessen the carcinogenic effects of breast irradiation, most likely by reducing exposure of radiation-damaged breast cells to stimulating effects of ovarian hormones. C1 [Inskip, Peter D.] NCI, NIH, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. Ohio State Univ, Sch Med, Nationwide Childrens Hosp, Dept Pathol, Columbus, OH 43210 USA. Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Dept Radiat Oncol, Stanford, CA 94305 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. RP Inskip, PD (reprint author), NCI, NIH, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 7052, Bethesda, MD 20892 USA. EM inskippe@mail.nih.gov FU NCI NIH HHS [U24 CA055727] NR 23 TC 97 Z9 97 U1 2 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2009 VL 27 IS 24 BP 3901 EP 3907 DI 10.1200/JCO.2008.20.7738 PG 7 WC Oncology SC Oncology GA 484RG UT WOS:000269064300007 PM 19620485 ER PT J AU Chen, RC Clark, JA Talcott, JA AF Chen, Ronald C. Clark, Jack A. Talcott, James A. TI Individualizing Quality-of-Life Outcomes Reporting: How Localized Prostate Cancer Treatments Affect Patients With Different Levels of Baseline Urinary, Bowel, and Sexual Function SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; CAPSURE; BRACHYTHERAPY; BOTHER; RADIOTHERAPY; SYMPTOMS; ANTIGEN AB Purpose Although it is the most powerful predictor of early prostate cancer treatment-related complications and quality-of-life (QOL) outcomes, most studies do not stratify results by baseline function. Further, reporting functional outcomes as averaged numerical results may obscure informatively disparate courses. Using levels of treatment-related dysfunction, we address these problems and present the final QOL outcomes of our prospective cohort study of patients with early prostate cancer. Methods We created categories for sexual, bowel, and urinary function, measured using numerical scores of the validated Prostate Cancer Symptom Indices and stratified into "normal," "intermediate" and "poor" levels of function by incorporating patient-reported symptom and distress information. We present QOL outcomes for 409 patients 36 months after radical prostatectomy, external-beam radiation therapy, and brachytherapy. Results Different levels of baseline sexual, bowel, and urinary function produced distinctive treatment-related changes from baseline to 36 months. In general, the average scale increases in dysfunction were greatest among patients with normal baseline function, although patients with normal and intermediate baseline function had similar increases in sexual dysfunction. For patients whose baseline urinary obstruction/irritation was poor, both average scale scores and most patients' level of function improved after treatment, particularly after surgery. Conclusion The use of functional levels to stratify treatment-related outcomes by pretreatment functional status and to display the proportions of patients with improved, stable, or worsened function after treatment provides information that more specifically conveys the expected impact of treatment to patients choosing among localized prostate cancer treatments. C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA USA. Harvard Radiat Oncol Program, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Outcomes Res, Bldg 120,210 6th St,2nd Floor, Charlestown, MA 02129 USA. EM jtalcott@partners.org OI Clark, Jack/0000-0002-7424-1670 FU AHRQ HHS [HS08208] NR 35 TC 98 Z9 99 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2009 VL 27 IS 24 BP 3916 EP 3922 DI 10.1200/JCO.2008.18.6486 PG 7 WC Oncology SC Oncology GA 484RG UT WOS:000269064300009 PM 19620493 ER PT J AU D'Amico, AV Moran, BJ Braccioforte, MH Dosoretz, D Salenius, S Katin, M Ross, R Chen, MH AF D'Amico, Anthony V. Moran, Brian J. Braccioforte, Michelle H. Dosoretz, Daniel Salenius, Sharon Katin, Michael Ross, Rudi Chen, Ming-Hui TI Risk of Death From Prostate Cancer After Brachytherapy Alone or With Radiation, Androgen Suppression Therapy, or Both in Men With High-Risk Disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EXTERNAL-BEAM RADIOTHERAPY; DOSE-RATE BRACHYTHERAPY; RELAPSE-FREE SURVIVAL; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; DEFINITIVE RADIOTHERAPY; RADICAL PROSTATECTOMY; DEPRIVATION THERAPY; HORMONAL-THERAPY; COMPETING RISK AB Purpose We estimated the risk of prostate cancer (PC) -specific mortality (PCSM) after brachytherapy alone or in conjunction with androgen suppression therapy (AST), external-beam radiation therapy (EBRT), or both in men with high-risk PC. Patients and Methods The study cohort comprised 1,342 men with a prostate-specific antigen level more than 20 ng/mL and clinical T3 or 4 and/or Gleason score 8 to 10 disease. Competing risks multivariable regression was performed to estimate the risk of PCSM in men treated with brachytherapy alone or with supplemental AST, EBRT, or both, adjusting for age, year of treatment, and known PC prognostic factors. Results Despite higher baseline probabilities of PCSM after a median follow-up of 5.1 years, there was a significant reduction in the risk of PCSM ( adjusted hazard ratio [AHR], 0.32; 95% CI, 0.14 to 0.73; P = .006) in men treated with brachytherapy and both AST and EBRT as compared with neither. When compared with brachytherapy alone, a significant decrease in the risk of PCSM was not observed in men treated with either supplemental AST (AHR, 0.63; 95% CI, 0.27 to 1.47; P = .28) or EBRT (AHR, 0.57; 95% CI, 0.21 to 1.52; P = .26). There was a near-significant reduction ( AHR, 0.53; 95% CI, 0.27 to 1.07; P = .079) in the risk of PCSM in men treated with tri- as compared with bimodality therapy. Conclusion Supplemental AST and EBRT but not either supplement compared with brachytherapy alone was associated with a decreased risk of PCSM in men with high-risk PC. C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Prostate Canc Fdn Chicago, Dept Radiat Oncol, Westmont, IL USA. 21st Century Oncol, Ft Myers, FL USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@partners.org NR 46 TC 39 Z9 42 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2009 VL 27 IS 24 BP 3923 EP 3928 DI 10.1200/JCO.2008.20.3992 PG 6 WC Oncology SC Oncology GA 484RG UT WOS:000269064300010 PM 19597029 ER PT J AU Grover, S Stoffel, EM Mercado, RC Ford, BM Kohlman, WK Shannon, KM Conrad, PG Blanco, AM Terdiman, JP Gruber, SB Chung, DC Syngal, S AF Grover, Shilpa Stoffel, Elena M. Mercado, Rowena C. Ford, Beth M. Kohlman, Wendy K. Shannon, Kristen M. Conrad, Peggy G. Blanco, Amie M. Terdiman, Jonathan P. Gruber, Stephen B. Chung, Daniel C. Syngal, Sapna TI Colorectal Cancer Risk Perception on the Basis of Genetic Test Results in Individuals at Risk for Lynch Syndrome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/107th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-24, 2006 CL Los Angeles, CA SP Amer Gastroenterol Assoc ID NONPOLYPOSIS COLON-CANCER; PERCEIVED RISK; BREAST-CANCER; HEREDITARY; WOMEN; FAMILIES; MUTATION; PREDISPOSITION; GUIDELINES; POLYPOSIS AB Purpose Lynch syndrome is associated with inherited germline mutations in mismatch repair (MMR) genes. Genetic testing in high-risk individuals may yield indeterminate results if no mutation is found or if a mutation of unclear pathogenic significance is observed. There are limited data regarding how well patients with Lynch syndrome understand the clinical implications of genetic test results. This study examines colorectal cancer (CRC) risk perception in individuals tested for MMR mutations and identifies the factors associated with an appropriate interpretation of their cancer risk. Patients and Methods A total of 159 individuals who met the Revised Bethesda Guidelines and had previously undergone genetic testing completed a questionnaire eliciting demographic data, cancer history, genetic test results, and an estimate of their CRC risk. Associations between clinical factors, genetic test results, and CRC risk perception were explored using multivariable analyses. Results Of the 100 individuals with a pathogenic mutation (true positive), 90 (90%) correctly estimated their CRC risk as "high" or "very high" compared with other individuals their age. However, only 23 (62%) of 37 individuals with an indeterminate genetic test result correctly estimated their risk. Individuals with a history of Lynch syndrome-associated cancer (odds ratio [OR], 0.1; 95% CI, 0.1 to 0.6) or indeterminate genetic test results (OR, 0.2; 95% CI, 0.1 to 0.6) were significantly less likely to estimate their CRC risk as increased. Conclusion Patients at risk for Lynch syndrome with an indeterminate genetic test result may be falsely reassured. It is important that health care providers continue to discuss the implications of uninformative results on lifetime cancer risk. C1 [Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. Univ Michigan, Dept Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA USA. Univ Utah, Huntsman Canc Inst, High Risk Canc Clin, Salt Lake City, UT USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, 44 Binney St,Smith 209, Boston, MA 02114 USA. EM ssyngal@partners.org FU NCI NIH HHS [K24 CA113433, K07 CA120448, K07 CA120448-01-A1] NR 26 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2009 VL 27 IS 24 BP 3981 EP 3986 DI 10.1200/JCO.2008.18.6940 PG 6 WC Oncology SC Oncology GA 484RG UT WOS:000269064300019 PM 19620492 ER PT J AU Patel, RB Burke, TF AF Patel, Ronak B. Burke, Thomas F. TI GLOBAL HEALTH Urbanization - An Emerging Humanitarian Disaster SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Patel, Ronak B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Burke, Thomas F.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Burke, Thomas F.] Harvard Univ, Sch Med, Boston, MA USA. RP Patel, RB (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 5 TC 53 Z9 54 U1 0 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 20 PY 2009 VL 361 IS 8 BP 741 EP 743 DI 10.1056/NEJMp0810878 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 484WX UT WOS:000269081200002 PM 19692687 ER PT J AU Smith, MR Egerdie, B Toriz, NH Feldman, R Tammela, TLJ Saad, F Heracek, J Szwedowski, M Ke, CL Kupic, A Leder, BZ Goessl, C AF Smith, Matthew R. Egerdie, Blair Hernndez Toriz, Narciso Feldman, Robert Tammela, Teuvo L. J. Saad, Fred Heracek, Jiri Szwedowski, Maciej Ke, Chunlei Kupic, Amy Leder, Benjamin Z. Goessl, Carsten CA Denosumab HALT Prostate Canc Study TI Denosumab in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; BONE-MINERAL DENSITY; ZOLEDRONIC ACID; POSTMENOPAUSAL WOMEN; OSTEOPOROSIS; FRACTURES; RISK; COMPLICATIONS; ALENDRONATE; PLACEBO AB BACKGROUND Androgen-deprivation therapy is well-established for treating prostate cancer but is associated with bone loss and an increased risk of fracture. We investigated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappa B ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. METHODS In this double-blind, multicenter study, we randomly assigned patients to receive denosumab at a dose of 60 mg subcutaneously every 6 months or placebo (734 patients in each group). The primary end point was percent change in bone mineral density at the lumbar spine at 24 months. Key secondary end points included percent change in bone mineral densities at the femoral neck and total hip at 24 months and at all three sites at 36 months, as well as incidence of new vertebral fractures. RESULTS At 24 months, bone mineral density of the lumbar spine had increased by 5.6% in the denosumab group as compared with a loss of 1.0% in the placebo group (P<0.001); significant differences between the two groups were seen at as early as 1 month and sustained through 36 months. Denosumab therapy was also associated with significant increases in bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. Patients who received denosumab had a decreased incidence of new vertebral fractures at 36 months (1.5%, vs. 3.9% with placebo) (relative risk, 0.38; 95% confidence interval, 0.19 to 0.78; P=0.006). Rates of adverse events were similar between the two groups. CONCLUSIONS Denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. (ClinicalTrials.gov number, NCT00089674.) C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Leder, Benjamin Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Egerdie, Blair] Urol Associates Urol Med Res, Kitchener, ON, Canada. [Hernndez Toriz, Narciso] Ctr Med Nacl Siglo XXI, Mexico City, DF, Mexico. [Feldman, Robert] Connecticut Clin Res Ctr Urol Specialists, Middlebury, VT USA. [Tammela, Teuvo L. J.] Tampere Univ Hosp, Tampere, Finland. [Heracek, Jiri] Androgeos, Prague, Czech Republic. [Saad, Fred] CHU Montreal, Montreal, PQ, Canada. [Szwedowski, Maciej] Wojewodzkie Ctr Med, Opole, Poland. [Ke, Chunlei; Kupic, Amy; Goessl, Carsten] Amgen Inc, Thousand Oaks, CA USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu RI Lamy, Olivier/E-5512-2013 FU Amgen; National Institutes of Health [5K24CA121990-02]; Prostate Cancer Foundation FX Supported by grants from Amgen, the National Institutes of Health (K24 Midcareer Investigator Award 5K24CA121990-02, to Dr. Smith), and the Prostate Cancer Foundation (to Dr. Smith). NR 37 TC 461 Z9 474 U1 2 U2 13 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 20 PY 2009 VL 361 IS 8 BP 745 EP 755 DI 10.1056/NEJMoa0809003 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 484WX UT WOS:000269081200003 PM 19671656 ER PT J AU Mouridsen, H Giobbie-Hurder, A Goldhirsch, A Thurlimann, B Paridaens, R Smith, I Mauriac, L Forbes, JF Price, KN Regan, MM Gelber, RD Coates, AS AF Mouridsen, Henning Giobbie-Hurder, Anita Goldhirsch, Aron Thuerlimann, Beat Paridaens, Robert Smith, Ian Mauriac, Louis Forbes, John F. Price, Karen N. Regan, Meredith M. Gelber, Richard D. Coates, Alan S. CA Big 1-98 Collaborative Grp TI Letrozole Therapy Alone or in Sequence with Tamoxifen in Women with Breast Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ADJUVANT ENDOCRINE THERAPY; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; AROMATASE INHIBITORS; CONTINUED TAMOXIFEN; ANASTROZOLE; SURVIVAL; EXEMESTANE; ARNO-95 AB BACKGROUND The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone. METHODS In this randomized, phase 3, double-blind trial of the treatment of hormone-receptor-positive breast cancer in postmenopausal women, we randomly assigned women to receive 5 years of tamoxifen monotherapy, 5 years of letrozole monotherapy, or 2 years of treatment with one agent followed by 3 years of treatment with the other. We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol-specified updated analysis of letrozole versus tamoxifen monotherapy in 4922 women. RESULTS At a median follow-up of 71 months after randomization, disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone (hazard ratio for tamoxifen followed by letrozole, 1.05; 99% confidence interval [CI], 0.84 to 1.32; hazard ratio for letrozole followed by tamoxifen, 0.96; 99% CI, 0.76 to 1.21). There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone. The updated analysis of monotherapy showed that there was a nonsignificant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen (hazard ratio for letrozole, 0.87; 95% CI, 0.75 to 1.02; P = 0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy. CONCLUSIONS Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with letrozole monotherapy, did not improve disease-free survival. The difference in overall survival with letrozole monotherapy and tamoxifen monotherapy was not statistically significant. (ClinicalTrials.gov number, NCT00004205.) C1 [Mouridsen, Henning] Vejle Hosp, Rigshosp, Danish Breast Canc Grp, Copenhagen, Denmark. [Giobbie-Hurder, Anita; Price, Karen N.; Regan, Meredith M.; Gelber, Richard D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. [Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Med, Boston, MA USA. [Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Goldhirsch, Aron] Oncol Inst So Switzerland, Bellinzona, Switzerland. [Thuerlimann, Beat] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Thuerlimann, Beat] Swiss Grp Clin Canc Res, Bern, Switzerland. [Paridaens, Robert] Catholic Univ Louvain, Univ Hosp Gasthuisberg, Dept Med Oncol, B-3000 Leuven, Belgium. [Smith, Ian] Royal Marsden Hosp, London SW3 6JJ, England. [Smith, Ian] Royal Marsden Natl Hlth Serv Trust, Sutton, Surrey, England. [Mauriac, Louis] Inst Bergonie, Federat Natl Ctr Lutte Canc, Bordeaux, France. [Forbes, John F.] Univ Newcastle, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2308, Australia. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. RP Mouridsen, H (reprint author), Vejle Hosp, Rigshosp, Danish Breast Canc Grp, Copenhagen, Denmark. RI IBIS, BIOMARCADORES/P-3515-2015; Rimassa, Lorenza/N-4884-2016; Gladieff, Laurence/O-5129-2014 OI Rimassa, Lorenza/0000-0001-9957-3615; Gladieff, Laurence/0000-0002-6980-9719 FU Novartis; Swedish Cancer Society; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research; National Cancer Institute [CA-75362]; Cancer Research Switzerland and Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland FX Supported by Novartis. The International Breast Cancer Study Group (IBCSG), which coordinated the study, is also supported by the Swedish Cancer Society, the Cancer Council Australia, the Australian New Zealand Breast Cancer Trials Group, the Frontier Science and Technology Research Foundation, the Swiss Group for Clinical Cancer Research, the National Cancer Institute (CA-75362), Cancer Research Switzerland and Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland. NR 34 TC 250 Z9 254 U1 3 U2 18 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 20 PY 2009 VL 361 IS 8 BP 766 EP 776 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 484WX UT WOS:000269081200005 ER PT J AU Freedman, SD Uppot, RN Mino-Kenudson, M AF Freedman, Steven D. Uppot, Raul N. Mino-Kenudson, Mari TI A Man with Cystic Fibrosis with Abdominal Pain and Distention Pseudomembranous colitis and enteritis, features consistent with Clostridium difficile enterocolitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COLONOPATHY C1 [Freedman, Steven D.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Uppot, Raul N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Freedman, Steven D.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Uppot, Raul N.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Freedman, SD (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. NR 16 TC 4 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 20 PY 2009 VL 361 IS 8 BP 807 EP 816 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 484WX UT WOS:000269081200011 PM 19692693 ER PT J AU Krumholz, HM Wang, Y Chen, J Drye, EE Spertus, JA Ross, JS Curtis, JP Nallamothu, BK Lichtman, JH Havranek, EP Masoudi, FA Radford, MJ Han, LF Rapp, MT Straube, BM Normand, SLT AF Krumholz, Harlan M. Wang, Yun Chen, Jersey Drye, Elizabeth E. Spertus, John A. Ross, Joseph S. Curtis, Jeptha P. Nallamothu, Brahmajee K. Lichtman, Judith H. Havranek, Edward P. Masoudi, Frederick A. Radford, Martha J. Han, Lein F. Rapp, Michael T. Straube, Barry M. Normand, Sharon-Lise T. TI Reduction in Acute Myocardial Infarction Mortality in the United States Risk-Standardized Mortality Rates From 1995-2006 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY-OF-CARE; NATIONAL REGISTRY; HOSPITAL MORTALITY; TRENDS; MEDICARE; IMPROVEMENT; ELEVATION; COMMUNITY; OUTCOMES; PROGRAM AB Context During the last 2 decades, health care professional, consumer, and payer organizations have sought to improve outcomes for patients hospitalized with acute myocardial infarction (AMI). However, little has been reported about improvements in hospital short-term mortality rates or reductions in between-hospital variation in short-term mortality rates. Objective To estimate hospital-level 30-day risk-standardized mortality rates (RSMRs) for patients discharged with AMI. Design, Setting, and Patients Observational study using administrative data and a validated risk model to evaluate 3 195 672 discharges in 2 755 370 patients discharged from nonfederal acute care hospitals in the United States between January 1, 1995, and December 31, 2006. Patients were 65 years or older (mean, 78 years) and had at least a 12-month history of fee-for-service enrollment prior to the index hospitalization. Patients discharged alive within 1 day of an admission not against medical advice were excluded, because it is unlikely that these patients had sustained an AMI. Main Outcome Measure Hospital-specific 30-day all-cause RSMR. Results At the patient level, the odds of dying within 30 days of admission if treated at a hospital 1 SD above the national average relative to that if treated at a hospital 1 SD below the national average were 1.63 (95% CI, 1.60-1.65) in 1995 and 1.56 (95% CI, 1.53-1.60) in 2006. In terms of hospital-specific RSMRs, a decrease from 18.8% in 1995 to 15.8% in 2006 was observed (odds ratio, 0.76; 95% CI, 0.75-0.77). A reduction in between-hospital heterogeneity in the RSMRs was also observed: the coefficient of variation decreased from 11.2% in 1995 to 10.8%, the interquartile range from 2.8% to 2.1%, and the between-hospital variance from 4.4% to 2.9%. Conclusion Between 1995 and 2006, the risk-standardized hospital mortality rate for Medicare patients discharged with AMI showed a significant decrease, as did between-hospital variation. JAMA. 2009;302(7):767-773 C1 [Krumholz, Harlan M.; Wang, Yun; Chen, Jersey; Drye, Elizabeth E.; Curtis, Jeptha P.] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Hlth Policy & Adm, Sch Publ Hlth, New Haven, CT 06510 USA. [Lichtman, Judith H.] Yale Univ, Sch Med, Sect Chron Dis Epidemiol, Sch Publ Hlth, New Haven, CT 06510 USA. [Krumholz, Harlan M.; Wang, Yun] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Spertus, John A.] Univ Missouri Kansas City, Sch Med, Kansas City, MO USA. [Spertus, John A.] Mid Amer Heart Inst, Kansas City, MO USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Ross, Joseph S.] James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Ross, Joseph S.] Hlth Serv Res Enhancement Award Program, Bronx, NY USA. [Nallamothu, Brahmajee K.] Univ Michigan, Sch Med, Hlth Serv Res & Dev Ctr Excellence, Ann Arbor VA Med Ctr, Ann Arbor, MI USA. [Nallamothu, Brahmajee K.] Univ Michigan, Sch Med, Div Cardiovasc Dis, Dept Internal Med, Ann Arbor, MI USA. [Havranek, Edward P.; Masoudi, Frederick A.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Havranek, Edward P.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. [Radford, Martha J.] NYU, Sch Med, New York, NY USA. [Han, Lein F.; Rapp, Michael T.; Straube, Barry M.] Ctr Medicare, Baltimore, MD USA. [Han, Lein F.; Rapp, Michael T.; Straube, Barry M.] Ctr Medicaid Serv, Baltimore, MD USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Sect Cardiovasc Med, 1 Church St,Ste 200, New Haven, CT 06510 USA. EM harlan.krumholz@yale.edu FU Centers for Medicare & Medicaid Services (CMS); US Department of Health and Human Services; [HHSM-500-2005-CO001C] FX The analyses on which this article is based were performed under contract HHSM-500-2005-CO001C, "Utilization and Quality Control Quality Improvement Organization for the State (commonwealth) of Colorado," funded by the Centers for Medicare & Medicaid Services (CMS), an agency of the US Department of Health and Human Services. NR 21 TC 125 Z9 129 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 19 PY 2009 VL 302 IS 7 BP 767 EP 773 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 484UT UT WOS:000269073800025 PM 19690309 ER PT J AU Laverdiere, C Liu, Q Yasui, Y Nathan, PC Gurney, JG Stovall, M Diller, LR Cheung, NK Wolden, S Robison, LL Sklar, CA AF Laverdiere, Caroline Liu, Qi Yasui, Yutaka Nathan, Paul C. Gurney, James G. Stovall, Marilyn Diller, Lisa R. Cheung, Nai-Kong Wolden, Suzanne Robison, Leslie L. Sklar, Charles A. TI Long-term Outcomes in Survivors of Neuroblastoma: A Report From the Childhood Cancer Survivor Study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ADVANCED-STAGE NEUROBLASTOMA; BONE-MARROW-TRANSPLANTATION; 2ND MALIGNANT NEOPLASMS; HIGH-RISK NEUROBLASTOMA; 5-YEAR SURVIVORS; LATE MORTALITY; NORDIC COUNTRIES; ADULT SURVIVORS; CHILDREN; CHEMOTHERAPY AB Background The 5-year survival rate for individuals with neuroblastoma is approaching 70%. Few data exist, however, on the long-term outcomes of these patients, who are often treated at a very young age. Methods Outcome data were obtained for 954 5-year neuroblastoma survivors who were diagnosed in 1970-1986 and enrolled in the Childhood Cancer Survivor Study (CCSS). Late mortality, second malignant neoplasms, and chronic health conditions were analyzed in relation to treatment factors using Poisson regression models and their modification with generalized estimating equations. Neuroblastoma survivors were compared with a cohort of 3899 siblings of CCSS participants for risk of chronic health conditions and selected sociodemographic outcomes. All statistical tests were two-sided. Results Six percent of patients died more than 5 years after their diagnosis (standardized mortality ratio = 5.6; 95% confidence interval [CI] = 4.4 to 6.9). The most common causes of death were disease recurrence (n = 43) and second malignant neoplasms (n = 13). The cumulative incidence of second malignant neoplasms was 3.5% at 25 years and 7.0% at 30 years after diagnosis. Compared with the sibling cohort, survivors had an increased risk of selected chronic health conditions (risk ratio [RR] = 8.3; 95% CI = 7.1 to 9.7) with a 20-year cumulative incidence of 41.1%. The most prevalent outcomes involved the neurological, sensory, endocrine, and musculoskeletal systems, with 20-year cumulative incidences of 29.8%, 8.6%, 8.3%, and 7.8%, respectively. Neuroblastoma survivors who were treated with multimodality therapy were more likely to develop a chronic health condition than survivors treated with surgery alone (RR = 2.2; 95% CI = 1.6 to 3.0). Neuroblastoma survivors were less likely than siblings to have ever been employed (P = .04) or to be married (P < .001) and had a lower personal income (P = .009). Conclusions Neuroblastoma survivors have an increased rate of mortality and second malignant neoplasms, relative to the age- and sex-comparable US population, and of chronic health conditions, relative to their siblings, which underscores the need for long-term medical surveillance. C1 [Laverdiere, Caroline] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. [Liu, Qi; Yasui, Yutaka] Univ Alberta, Dept Publ Hlth Sci, Sch Publ Hlth, Edmonton, AB, Canada. [Nathan, Paul C.] Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada. [Gurney, James G.] Univ Michigan, Dept Pediat, Child Hlth Evaluat & Res Unit, Ann Arbor, MI 48109 USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Diller, Lisa R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Cheung, Nai-Kong; Sklar, Charles A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Wolden, Suzanne] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Robison, Leslie L.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. RP Laverdiere, C (reprint author), Hop St Justine, 3175 Cote St Catherine, Montreal, PQ H3T 1C5, Canada. EM caroline.laverdiere@umontreal.ca RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU National Cancer Institute [U24 CA55727]; American Lebanese Syrian Associated Charities (St. Jude Children's Research Hospital; National Cancer Institute of Canada; Terry Fox Run FX CCSS is supported by a grant from the National Cancer Institute (U24 CA55727 to L.L.R.) and the American Lebanese Syrian Associated Charities (St. Jude Children's Research Hospital). National Cancer Institute of Canada with funds from the Terry Fox Run (C.L.). NR 43 TC 55 Z9 56 U1 3 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 AUG 19 PY 2009 VL 101 IS 16 BP 1131 EP 1140 DI 10.1093/jnci/djp230 PG 10 WC Oncology SC Oncology GA 484XY UT WOS:000269084800010 PM 19648511 ER PT J AU Margolis, ML AF Margolis, Mitchell L. TI The PET and the Pendulum SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID CELL LUNG-CANCER; POSITRON-EMISSION-TOMOGRAPHY; RANDOMIZED-TRIAL; VOLUME-REDUCTION; CT; MANAGEMENT; EMPHYSEMA; STANDARD C1 [Margolis, Mitchell L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Margolis, Mitchell L.] Univ Penn, Philadelphia, PA 19104 USA. RP Margolis, ML (reprint author), Philadelphia Vet Affairs Med Ctr, Room 8A112 Clin Addit, Philadelphia, PA 19104 USA. EM mitchell.margolis@med.va.gov NR 18 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 18 PY 2009 VL 151 IS 4 BP 279 EP 280 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 484IW UT WOS:000269038900009 PM 19581638 ER PT J AU Marder, S AF Marder, Steven TI Both typical and atypical antipsychotic agents were associated with increased risk for sudden cardiac death Commentary SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 US Dept Vet Affairs, Los Angeles, CA USA. RP Marder, S (reprint author), US Dept Vet Affairs, Los Angeles, CA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 18 PY 2009 VL 151 IS 4 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 484IW UT WOS:000269038900041 ER PT J AU Dorph-Petersen, KA Delevich, KM Marcsisin, MJ Zhang, W Sampson, AR Gundersen, HJG Lewis, DA Sweet, RA AF Dorph-Petersen, Karl-Anton Delevich, Kristen M. Marcsisin, Michael J. Zhang, Wei Sampson, Allan R. Gundersen, Hans Jorgen G. Lewis, David A. Sweet, Robert A. TI Pyramidal neuron number in layer 3 of primary auditory cortex of subjects with schizophrenia SO BRAIN RESEARCH LA English DT Article DE Auditory; Cerebral cortex; Schizophrenia; Pyramidal neuron; Stereology; Post-mortem ID DENDRITIC SPINE DENSITY; UNBIASED STEREOLOGICAL ESTIMATION; MISMATCH NEGATIVITY GENERATION; SUPERIOR TEMPORAL GYRUS; PREFRONTAL CORTEX; PLANUM TEMPORALE; MACAQUE MONKEYS; 1ST-EPISODE SCHIZOPHRENIA; CORTICAL DYSFUNCTION; ALZHEIMERS-DISEASE AB Individuals with schizophrenia demonstrate impairments of sensory processing within primary auditory cortex. We have previously identified lower densities of dendritic spines and axon boutons, and smaller mean pyramidal neuron somal volume, in layer 3 of the primary auditory cortex in subjects with schizophrenia, all of which might reflect fewer layer 3 pyramidal neurons in schizophrenia. To examine this hypothesis, we developed a robust stereological. method based upon unbiased principles for estimation of total volume and pyramidal neuron numbers for each layer of a cortical area. Our method generates both a systematic, uniformly random set of mapping sections as well as a set of randomly rotated sections cut orthogonal to the pial surface, within the region of interest. We applied our approach in twelve subjects with schizophrenia, each matched to a normal comparison subject. Primary auditory cortex volume was assessed using Cavalieri's method. The relative and absolute volume of each cortical layer and, within layer 3, the number and density of pyramidal neurons were estimated using our novel approach. Subject groups did not differ in regional volume, layer volumes, or pyramidal neuron number, although pyramidal neuron density was significantly greater in subjects with schizophrenia. These findings suggest that previously observed lower densities of dendritic spines and axon boutons reflect fewer numbers per neuron, and contribute to greater neuronal density via a reduced neuropil. Our approach represents a powerful new method for stereologic estimation of features of interest within individual layers of cerebral cortex, with applications beyond the current study. (C) 2009 Elsevier B.V. All rights reserved. C1 [Dorph-Petersen, Karl-Anton; Delevich, Kristen M.; Marcsisin, Michael J.; Lewis, David A.; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Dorph-Petersen, Karl-Anton] Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark. [Zhang, Wei; Sampson, Allan R.] Univ Pittsburgh, Dept Stat, Pittsburgh, PA USA. [Gundersen, Hans Jorgen G.] Univ Aarhus, Stereol & Electron Microscopy Res Lab, Aarhus, Denmark. [Gundersen, Hans Jorgen G.] Univ Aarhus, MIND Ctr, Aarhus, Denmark. [Lewis, David A.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Biomed Sci Tower,Rm W-1645,3811 OHara St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu RI Lewis, David/G-4053-2014; Dorph-Petersen, Karl-Anton/A-9039-2015; OI Lewis, David/0000-0002-3225-6778; Dorph-Petersen, Karl-Anton/0000-0002-6676-034X; Delevich, Kristen/0000-0001-5698-0093 FU USPHS [MH 071533, MH 045156, MH 084053] FX This work was supported by USPHS grants MH 071533, MH 045156 and MH 084053. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National institute of Mental Health or the National Institutes of Health. The authors would like to thank Professor Eva B.V. Jensen for consultation on the calculation of the coefficients of error for our estimators, and Mrs. Mary Brady for assistance with the figures. The authors gratefully acknowledge the efforts of the research staff of the Translational Neuroscience Program and the Conte Center for Neuroscience of Mental Disorders at the 'University of Pittsburgh. NR 76 TC 20 Z9 20 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 18 PY 2009 VL 1285 BP 42 EP 57 DI 10.1016/j.brainres.2009.06.019 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 487MB UT WOS:000269277300005 PM 19524554 ER PT J AU Viswanathan, AN Schernhammer, ES AF Viswanathan, Akila N. Schernhammer, Eva S. TI Circulating melatonin and the risk of breast and endometrial cancer in women SO CANCER LETTERS LA English DT Review DE Cancer; Treatment; Melatonin ID URINARY 6-SULFATOXYMELATONIN LEVELS; NOCTURNAL PLASMA MELATONIN; NIGHT-SHIFT WORK; ESTROGEN-RECEPTOR; SLEEP DURATION; CIRCADIAN DISRUPTION; VISUAL IMPAIRMENT; SERUM MELATONIN; UNITED-STATES; NURSES HEALTH AB Several decades of observational data have accumulated to implicate a potential role for melatonin in cancer prevention. Experimental studies suggest that the antineoplastic action of melatonin arises through many different mechanisms, including melatonin's antioxidant, antimitotic, and antiangiogenic activity, as well as its ability to modulate the immune system and alter fat metabolism. Melatonin interacts with membrane and nuclear receptors, and may be linked to the regulation of tumor growth. Of particular relevance to breast cancer risk, melatonin may also block the estrogen receptor ER alpha and impact the enzyme aromatase, which produces estradiol. A growing number of epidemiologic studies have evaluated the relationship between night shift work as well as how varying duration of sleep affects peak melatonin secretion at night. While the studies demonstrate lower nightly melatonin levels in night workers, the evidence for an association between sleep duration and melatonin production is less clear. Similarly, both case-control and prospective cohort studies have consistently linked night shift work with breast cancer risk and, more recently, endometrial cancer - another tumor highly sensitive to estrogens. While, to date, the evidence for an association between sleep duration and breast cancer risk is less convincing, overall, there is increasing support for a potentially important link between melatonin and breast cancer risk and perhaps the risk of other tumors. As evidence increases, modifiable factors that have been shown to affect melatonin production, such as night shift work, are likely to gain increasing recognition as potential public health hazards. Additional studies are needed to delineate further the potential of melatonin in cancer prevention. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Viswanathan, Akila N.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Viswanathan, Akila N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Schernhammer, Eva S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Schernhammer, Eva S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu FU NIH [5K07 CAI 17979-01]; NIH CAI [14534] FX Dr. Viswanathan receives support from NIH Grant 5K07 CAI 17979-01. Dr. Schernhammer is funded through the NIH CAI 14534. NR 85 TC 67 Z9 70 U1 2 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 18 PY 2009 VL 281 IS 1 BP 1 EP 7 DI 10.1016/j.canlet.2008.11.002 PG 7 WC Oncology SC Oncology GA 465KD UT WOS:000267581600001 PM 19070424 ER PT J AU Milan, DJ Kim, AM Winterfield, JR Jones, IL Pfeufer, A Sanna, S Arking, DE Amsterdam, AH Sabeh, KM Mably, JD Rosenbaum, DS Peterson, RT Chakravarti, A Kaab, S Roden, DM MacRae, CA AF Milan, David J. Kim, Albert M. Winterfield, Jeffrey R. Jones, Ian L. Pfeufer, Arne Sanna, Serena Arking, Dan E. Amsterdam, Adam H. Sabeh, Khaled M. Mably, John D. Rosenbaum, David S. Peterson, Randall T. Chakravarti, Aravinda Kaeaeb, Stefan Roden, Dan M. MacRae, Calum A. TI Drug-Sensitized Zebrafish Screen Identifies Multiple Genes, Including GINS3, as Regulators of Myocardial Repolarization SO CIRCULATION LA English DT Article DE electrophysiology; genes; ion channels; myocardial repolarization ID LONG-QT SYNDROME; MODULATES CARDIAC REPOLARIZATION; INTERVAL DURATION; COMMON VARIANTS; ATRIOVENTRICULAR-BLOCK; MOLECULAR PHYSIOLOGY; CONCENTRIC GROWTH; HEART; SODIUM; RISK AB Background-Cardiac repolarization, the process by which cardiomyocytes return to their resting potential after each beat, is a highly regulated process that is critical for heart rhythm stability. Perturbations of cardiac repolarization increase the risk for life-threatening arrhythmias and sudden cardiac death. Although genetic studies of familial long-QT syndromes have uncovered several key genes in cardiac repolarization, the major heritable contribution to this trait remains unexplained. Identification of additional genes may lead to a better understanding of the underlying biology, aid in identification of patients at risk for sudden death, and potentially enable new treatments for susceptible individuals. Methods and Results-We extended and refined a zebrafish model of cardiac repolarization by using fluorescent reporters of transmembrane potential. We then conducted a drug-sensitized genetic screen in zebrafish, identifying 15 genes, including GINS3, that affect cardiac repolarization. Testing these genes for human relevance in 2 concurrently completed genome-wide association studies revealed that the human GINS3 ortholog is located in the 16q21 locus, which is strongly associated with QT interval. Conclusions-This sensitized zebrafish screen identified 15 novel myocardial repolarization genes. Among these genes is GINS3, the human ortholog of which is a major locus in 2 concurrent human genome-wide association studies of QT interval. These results reveal a novel network of genes that regulate cardiac repolarization. (Circulation. 2009;120:553-559.) C1 [Milan, David J.; Kim, Albert M.; Winterfield, Jeffrey R.; Jones, Ian L.; Sabeh, Khaled M.; Peterson, Randall T.; MacRae, Calum A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Milan, David J.; Kim, Albert M.; Winterfield, Jeffrey R.; Jones, Ian L.; Sabeh, Khaled M.; Peterson, Randall T.; MacRae, Calum A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Pfeufer, Arne] Germany Natl Res Ctr Environm Hlth, Helmholtz Ctr Munich, Dept Human Genet, Neuherberg, Germany. [Pfeufer, Arne] Tech Univ Munich, Dept Human Genet, Munich, Germany. [Sanna, Serena] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. [Arking, Dan E.; Chakravarti, Aravinda] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Amsterdam, Adam H.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Mably, John D.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Rosenbaum, David S.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Kaeaeb, Stefan] Univ Munich, Klinikum Grosshadern, Dept Med 1, D-8000 Munich, Germany. [Roden, Dan M.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Roden, Dan M.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. RP Milan, DJ (reprint author), Cardiovasc Res Ctr, 149 13th St,4th Floor, Charlestown, MA 02129 USA. EM dmilan@partners.org; cmacrae@partners.org RI Kaab, Stefan/H-3915-2012; Pfeufer, Arne/B-6634-2013; OI sanna, serena/0000-0002-3768-1749 FU National Institutes of Health [HL65962, GM075946, HL76361, RR012589-6]; National Institute of Aging [N01-AG-1-2109]; Fondation Leducq; German Federal Ministry of Education and Research [01GS0838] FX This work was supported by research grants from the National Institutes of Health: HL65962 (to Drs Roden, MacRae, and Milan), GM075946 (to Drs MacRae, Peterson, Rosenbaum, and Milan), HL76361 (to Dr Milan), and RR012589-6 (to Dr Amsterdam). The SardiNIA study was supported by the National Institute of Aging contract N01-AG-1-2109 to the SardiNIA (ProgeNIA) team. Dr Kaab is supported by a grant from the Fondation Leducq and the German Federal Ministry of Education and Research in the context of the German National Genome Research Network (01GS0838). NR 38 TC 57 Z9 57 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 18 PY 2009 VL 120 IS 7 BP 553 EP U33 DI 10.1161/CIRCULATIONAHA.108.821082 PG 15 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 484NH UT WOS:000269051900003 PM 19652097 ER PT J AU Brilakis, ES Hernandez, AF Dai, D Peterson, ED Banerjee, S Fonarow, GC Cannon, CP Bhatt, DL AF Brilakis, Emmanouil S. Hernandez, Adrian F. Dai, David Peterson, Eric D. Banerjee, Subhash Fonarow, Gregg C. Cannon, Christopher P. Bhatt, Deepak L. TI Quality of Care for Acute Coronary Syndrome Patients With Known Atherosclerotic Disease Results From the Get With the Guidelines Program SO CIRCULATION LA English DT Article DE peripheral vascular disease; stroke; coronary disease; acute coronary syndrome; quality assessment, healthcare ID PERIPHERAL ARTERIAL-DISEASE; ELEVATION MYOCARDIAL-INFARCTION; GLOBAL REGISTRY; ST-ELEVATION; OUTCOMES; EVENTS; ASSOCIATION; PREDICTORS; STROKE; TRIAL AB Background-Patients with prior atherosclerosis in 1 or more vascular territories (coronary, cerebrovascular, or peripheral arterial) who present with acute coronary syndromes have high cardiovascular risk and may benefit significantly from evidence-based therapies, yet whether these are used consistently is unknown. Methods and Results-The Get With the Guidelines-Coronary Artery Disease database was queried to determine whether compliance with quality-of-care treatments for acute coronary syndrome patients was associated with the extent of prior vascular disease. A total of 143 999 patients enrolled at 438 sites between January 2000 and January 2008 were classified according to the absence (n=98 136; 68%) or presence of known preexistent atherosclerosis (before admission) in 1, 2, or 3 vascular territories (n=37 633 [26%], n=7369 [5%], and n=861 [0.6%], respectively). Overall in-hospital mortality was 5.3%, and mean length of stay was 5.6 +/- 6.7 days. Compared with patients without prior vascular disease, patients with prior vascular disease were older and had more comorbidities. They were less likely to undergo coronary revascularization and had longer duration of hospital stay and higher in-hospital mortality. After adjustment for clinical and hospital characteristics, compared with patients without prior vascular disease, patients with prior vascular disease had higher mortality and were less likely to receive 3 particular treatments (lipid-lowering therapy, smoking cessation counseling, and angiotensin-converting enzyme inhibitor for left ventricular dysfunction). Conclusions-Compared with acute coronary syndrome patients without prior vascular disease, those with prior atherosclerosis had higher in-hospital mortality yet were paradoxically less likely to receive specific evidence-based acute coronary syndrome treatments, which can form the basis for targeted intervention. (Circulation. 2009;120:560-567.) C1 [Brilakis, Emmanouil S.; Banerjee, Subhash] VA N Texas Healthcare Syst, Dallas, TX USA. [Brilakis, Emmanouil S.; Banerjee, Subhash] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Hernandez, Adrian F.; Dai, David; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Hernandez, Adrian F.; Dai, David; Peterson, Eric D.] Duke Univ, Med Ctr, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Cannon, Christopher P.] TIMI Grp, Boston, MA USA. [Cannon, Christopher P.] Harvard Univ, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Brilakis, ES (reprint author), Dallas VA Med Ctr, 111A,4500 S Lancaster Rd, Dallas, TX 75216 USA. EM esbrilakis@yahoo.com RI Brilakis, Emmanouil/B-5282-2009; Hernandez, Adrian F./A-7818-2016; OI Hernandez, Adrian F./0000-0003-3387-9616; Brilakis, Emmanouil/0000-0001-9416-9701 FU Council on Clinical Cardiology of the American Heart Association; Merck/Schering-Plough; American Heart Association FX This study is supported by a grant from the Council on Clinical Cardiology of the American Heart Association. The GWTG program is funded in part by the Merck/Schering-Plough partnership. Data collection and management were performed by Outcome, Inc (Cambridge, Mass). The analysis of registry data was performed at Duke Clinical Research Institute (Durham, NC), which also receives funding from the American Heart Association. The sponsor was not involved in the management, analysis, or interpretation of the data or in the preparation of the manuscript. NR 22 TC 40 Z9 44 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 18 PY 2009 VL 120 IS 7 BP 560 EP 567 DI 10.1161/CIRCULATIONAHA.109.877092 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 484NH UT WOS:000269051900004 PM 19652090 ER PT J AU Ronald, JA Chen, JW Chen, YX Hamilton, AM Rodriguez, E Reynolds, F Hegele, RA Rogers, KA Querol, M Bogdanov, A Weissleder, R Rutt, BK AF Ronald, John A. Chen, John W. Chen, Yuanxin Hamilton, Amanda M. Rodriguez, Elisenda Reynolds, Fred Hegele, Robert A. Rogers, Kem A. Querol, Manel Bogdanov, Alexei Weissleder, Ralph Rutt, Brian K. TI Enzyme-Sensitive Magnetic Resonance Imaging Targeting Myeloperoxidase Identifies Active Inflammation in Experimental Rabbit Atherosclerotic Plaques SO CIRCULATION LA English DT Article DE magnetic resonance imaging; atherosclerosis; inflammation; myeloperoxidase; contrast media ID PLASMA-CHOLESTEROL LEVELS; IN-VIVO; CONTRAST AGENT; INVERSION-RECOVERY; CORONARY-DISEASE; LESIONS; MACROPHAGES; EXPRESSION; MONOCYTE; DETECTS AB Background-Inflammation undermines the stability of atherosclerotic plaques, rendering them susceptible to acute rupture, the cataclysmic event that underlies clinical expression of this disease. Myeloperoxidase is a central inflammatory enzyme secreted by activated macrophages and is involved in multiple stages of plaque destabilization and patient outcome. We report here that a unique functional in vivo magnetic resonance agent can visualize myeloperoxidase activity in atherosclerotic plaques in a rabbit model. Methods and Results-We performed magnetic resonance imaging of the thoracic aorta of New Zealand White rabbits fed a cholesterol (n=14) or normal (n=4) diet up to 2 hours after injection of the myeloperoxidase sensor bis-5HT-DTPA(Gd) [MPO(Gd)], the conventional agent DTPA(Gd), or an MPO( Gd) analog, bis-tyr-DTPA(Gd), as controls. Delayed MPO(Gd) images (2 hours after injection) showed focal areas of increased contrast (>2-fold) in diseased wall but not in normal wall (P=0.84) compared with both DTPA(Gd) (n=11; P<0.001) and bis-tyr-DTPA( Gd) (n=3; P<0.05). Biochemical assays confirmed that diseased wall possessed 3-fold elevated myeloperoxidase activity compared with normal wall (P<0.01). Areas detected by MPO(Gd) imaging colocalized and correlated with myeloperoxidase-rich areas infiltrated by macrophages on histopathological evaluations (r=0.91, P<0.0001). Although macrophages were the main source of myeloperoxidase, not all macrophages secreted myeloperoxidase, which suggests that distinct subpopulations contribute differently to atherogenesis and supports our functional approach. Conclusions-The present study represents a unique approach in the detection of inflammation in atherosclerotic plaques by examining macrophage function and the activity of an effector enzyme to noninvasively provide both anatomic and functional information in vivo. (Circulation. 2009;120:592-599.) C1 [Ronald, John A.; Chen, Yuanxin; Hegele, Robert A.; Rutt, Brian K.] Robarts Res Inst, London, ON N6A 5C1, Canada. [Ronald, John A.; Rutt, Brian K.] Univ Western Ontario, Dept Med Biophys, London, ON, Canada. [Hamilton, Amanda M.; Rogers, Kem A.] Univ Western Ontario, Dept Anat & Cell Biol, London, ON, Canada. [Rutt, Brian K.] Univ Western Ontario, Dept Diagnost Radiol & Nucl Med, London, ON, Canada. [Chen, John W.; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA USA. [Chen, John W.; Rodriguez, Elisenda; Reynolds, Fred; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Querol, Manel; Bogdanov, Alexei] Univ Massachusetts, Sch Med, Lab Mol Imaging Probes, Dept Radiol, Worcester, MA USA. [Ronald, John A.] Stanford Univ, Dept Radiol, Sch Med, Mol Imaging Program Stanford, Palo Alto, CA 94306 USA. RP Ronald, JA (reprint author), Stanford Univ, Dept Radiol, Sch Med, Mol Imaging Program Stanford, E150 James Clark Ctr,318 Campus Dr, Palo Alto, CA 94306 USA. EM jronald1@stanfor.edu; chenjo@helix.mgh.harvard.edu RI Ronald, John/B-7123-2008; Hegele, Robert/G-3301-2011 OI Ronald, John/0000-0003-3665-173X; FU National Institutes of Health [R01-HL078641, NIH 5K08HL081170]; Canadian Institutes of Health Research Heart and Stroke Foundation of Canada [CMI-72324]; Heart and Stroke Foundation of Canada; European Commission FX This work was funded in part by the National Institutes of Health (R01-HL078641 to Drs Weissleder and Rutt, NIH 5K08HL081170 to Dr John Chen) and the Canadian Institutes of Health Research Heart and Stroke Foundation of Canada (CMI-72324 to Dr Rutt). Dr Rutt holds the Barnett-Ivey Heart and Stroke Foundation of Ontario Research Chair. Dr Ronald holds the Great-West Life doctoral research award from the Heart and Stroke Foundation of Canada. Dr Rodriguez is supported by the Marie Curie fellowship from the European Commission. NR 39 TC 71 Z9 71 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 18 PY 2009 VL 120 IS 7 BP 592 EP U92 DI 10.1161/CIRCULATIONAHA.108.813998 PG 22 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 484NH UT WOS:000269051900008 PM 19652086 ER PT J AU An, XJ Jin, Y Guo, HN Foo, SY Cully, BL Wu, JP Zeng, HY Rosenzweig, A Li, J AF An, Xiaojin Jin, Yi Guo, Hongnian Foo, Shi-Yin Cully, Brittany L. Wu, Jiaping Zeng, Huiyan Rosenzweig, Anthony Li, Jian TI Response Gene to Complement 32, a Novel Hypoxia-Regulated Angiogenic Inhibitor SO CIRCULATION LA English DT Article DE angiogenesis; apoptosis; endothelium; gene therapy; hypoxia; ischemia ID SMOOTH-MUSCLE-CELLS; ENDOTHELIAL-CELLS; GROWTH; EXPRESSION; CANCER; VEGF; OVEREXPRESSION; FGF-2; MECHANISMS; APOPTOSIS AB Background-Response gene to complement 32 (RGC-32) is induced by activation of complement and regulates cell proliferation. To determine the mechanism of RGC-32 in angiogenesis, we examined the role of RGC-32 in hypoxia-related endothelial cell function. Methods and Results-Hypoxia/ischemia is able to stimulate both angiogenesis and apoptosis. Hypoxia-inducible factor-1/vascular endothelial growth factor is a key transcriptional regulatory pathway for angiogenesis during hypoxia. We demonstrated that the increased RGC-32 expression by hypoxia was via hypoxia-inducible factor-1/vascular endothelial growth factor induction in cultured endothelial cells. However, overexpression of RGC-32 reduced the proliferation and migration and destabilized vascular structure formation in vitro and inhibited angiogenesis in Matrigel assays in vivo. Silencing RGC-32 had an opposing, stimulatory effect. RGC-32 also stimulated apoptosis as shown by the increased apoptotic cells and caspase-3 cleavage. Mechanistic studies revealed that the effect of RGC-32 on the antiangiogenic response was via attenuating fibroblast growth factor 2 expression and further inhibiting expression of cyclin E without affecting vascular endothelial growth factor and fibroblast growth factor 2 signaling in endothelial cells. In the mouse hind-limb ischemia model, RGC-32 inhibited capillary density with a significant attenuation in blood flow. Additionally, treatment with RGC-32 in the xenograft tumor model resulted in reduced growth of blood vessels that is consistent with reduced colon tumor size. Conclusions-We provide the first direct evidence for RGC-32 as a hypoxia-inducible gene and antiangiogenic factor in endothelial cells. These data suggest that RGC-32 plays an important homeostatic role in that it contributes to differentiating the pathways for vascular endothelial growth factor and fibroblast growth factor 2 in angiogenesis and provides a new target for ischemic disorder and tumor therapies. (Circulation. 2009;120:617-627.) C1 [An, Xiaojin; Jin, Yi; Guo, Hongnian; Foo, Shi-Yin; Cully, Brittany L.; Wu, Jiaping; Rosenzweig, Anthony; Li, Jian] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Sch Med,Dept Med, Boston, MA 02115 USA. [An, Xiaojin; Jin, Yi; Li, Jian] Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. [Zeng, Huiyan] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Mol & Vasc Med, Sch Med,Dept Med, Boston, MA 02115 USA. RP Li, J (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Sch Med,Dept Med, 3 Blackfan Circle, Boston, MA 02115 USA. EM JLi@BIDMC.Harvard.edu FU National Institutes of Health [HLR01082837]; AHA [0265494T]; China Scholarship Council FX This work was supported in part by a National Institutes of Health grant HLR01082837 (Dr Li), an AHA grant-in-aid 0265494T (Dr Li), and the China Scholarship Council (X. An and Y. Jin). NR 31 TC 18 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 18 PY 2009 VL 120 IS 7 BP 617 EP U141 DI 10.1161/CIRCULATIONAHA.108.841502 PG 15 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 484NH UT WOS:000269051900011 PM 19652095 ER PT J AU O'Donoghue, M Antman, EM Braunwald, E Murphy, SA Steg, PG Finkelstein, A Penny, WF Fridrich, V McCabe, CH Sabatine, MS Wiviott, SD AF O'Donoghue, Michelle Antman, Elliott M. Braunwald, Eugene Murphy, Sabina A. Steg, P. Gabriel Finkelstein, Ariel Penny, William F. Fridrich, Viliam McCabe, Carolyn H. Sabatine, Marc S. Wiviott, Stephen D. TI The Efficacy and Safety of Prasugrel With and Without a Glycoprotein IIb/IIIa Inhibitor in Patients With Acute Coronary Syndromes Undergoing Percutaneous Intervention A TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) Analysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE prasugrel; clopidogrel; thienopyridine; glycoprotein IIb/IIIa inhibitor; platelets; acute coronary syndrome; percutaneous intervention ID ASPIRIN-TREATED PATIENTS; CLOPIDOGREL PRETREATMENT; ACHIEVES GREATER; ARTERY-DISEASE; AGGREGATION; ACTIVATION; ABCIXIMAB; CARE AB Objectives We evaluated the efficacy and safety of prasugrel and clopidogrel in the setting of a glycoprotein (GP) IIb/IIIa inhibitor. Background Prasugrel reduced cardiovascular events as compared with clopidogrel in TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38) but with increased bleeding. Methods Researchers in the TRITON-TIMI 38 randomized 13,608 subjects with acute coronary syndrome undergoing percutaneous coronary intervention to prasugrel versus clopidogrel. The use of a GP IIb/IIIa inhibitor was at the physician's discretion. For the current analysis, end points were examined at 30 days and were stratified by use of a GP IIb/IIIa inhibitor. Results A total of 7,414 subjects (54.5%) received a GP IIb/IIIa inhibitor during their index hospitalization. There was a consistent benefit of prasugrel over clopidogrel for reducing cardiovascular death, myocardial infarction, or stroke in patients who did (hazard ratio: 0.76; 95% confidence interval: 0.64 to 0.90) or did not receive a GP IIb/IIIa inhibitor (hazard ratio: 0.78; 95% confidence interval: 0.63 to 0.97, p(interaction) = 0.83). Prasugrel significantly reduced myocardial infarction, urgent revascularization, and stent thrombosis irrespective of GP IIb/IIIa inhibitor use. Although subjects treated with a GP IIb/IIIa inhibitor had greater rates of bleeding, the risk of Thrombolysis in Myocardial Infarction major or minor bleeding with prasugrel versus clopidogrel was not significantly different in patients who were or were not treated with GP IIb/IIIa inhibitor (pinteraction = 0.19). Conclusions Prasugrel significantly reduces the risk of cardiovascular events in patients with acute coronary syndromes after percutaneous coronary intervention regardless of whether or not a GP IIb/IIIa inhibitor is used. The use of a GP IIb/IIIa inhibitor does not accentuate the relative risk of bleeding with prasugrel as compared with clopidogrel. (J Am Coll Cardiol 2009; 54: 678-85) (C) 2009 by the American College of Cardiology Foundation C1 [O'Donoghue, Michelle; Antman, Elliott M.; Braunwald, Eugene; Murphy, Sabina A.; McCabe, Carolyn H.; Sabatine, Marc S.; Wiviott, Stephen D.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Steg, P. Gabriel] Univ Paris 07, AP HP, INSERM, U698, Paris, France. [Penny, William F.] Univ Calif San Diego, VA Med Ctr, San Diego, CA 92103 USA. [Fridrich, Viliam] Slovak Inst Cardiovasc Dis, Bratislava, Slovakia. [Finkelstein, Ariel] Tel Aviv Med Ctr & Sch Med, Tel Aviv, Israel. RP O'Donoghue, M (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Long Wood Ave,1st Floor, Boston, MA 02115 USA. EM modonoghue@partners.org NR 25 TC 58 Z9 58 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 18 PY 2009 VL 54 IS 8 BP 678 EP 685 DI 10.1016/j.jacc.2009.05.025 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482CT UT WOS:000268862200002 PM 19679245 ER PT J AU Yu, Z Liu, J Guo, S Xing, C Fan, X Ning, M Yuan, JC Lo, EH Wang, X AF Yu, Z. Liu, J. Guo, S. Xing, C. Fan, X. Ning, M. Yuan, J. C. Lo, E. H. Wang, X. TI NEUROGLOBIN-OVEREXPRESSION ALTERS HYPOXIC RESPONSE GENE EXPRESSION IN PRIMARY NEURON CULTURE FOLLOWING OXYGEN GLUCOSE DEPRIVATION SO NEUROSCIENCE LA English DT Article DE neuroglobin; oxygen glucose deprivation; hypoxic response genes; oligo GEArray hybridization ID NUCLEOTIDE DISSOCIATION INHIBITOR; FOCAL CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; BRAIN-INJURY; PC12 CELLS; PROTEIN; GLOBIN; MICE; NEUROPROTECTION; PLASTICITY AB Neuroglobin (Ngb) is a tissue globin specifically expressed in neurons. Our laboratory and others have shown that Ngb overexpression protects neurons against hypoxia/ischemia, but the underlying mechanisms remain poorly understood. Recent studies demonstrate that hypoxia/ischemia induces a multitude of spatially and temporally regulated responses in gene expression, and initial evidence suggested that Ngb might function in altering biological processes of gene expression. In this study, we asked how Ngb may help regulate genes responsive to hypoxia. Expression of hypoxic response genes following oxygen-glucose deprivation (OGD) was examined using mRNA arrays in neuroglobin-overexpressing transgenic (Ngb-Tg) and wild type (WT) mouse neurons. From a total of 113 genes on the microarray, mRNA expression of 65 genes was detected. Under rest condition, 14 genes were downregulated in Ngb-Tg neurons compared to WT. In WT neurons, after 4-h OGD followed by 4-h reoxygenation (O4/R4), 20 genes were significantly downregulated, and only Fos mRNA was significantly increased. However, out of the 20 downregulated genes in WT neurons, 12 of them were no longer significantly changed in Ngb-Tg neurons: Add1, Amt2, Camk2g, Cstb, Dr1, Epas1, Gna11, Hif1a, II6st, Khsrp, Mars and Rara. Among these 12 genes, 8 (Add1, Camk2g, Cstb, Dr1, Epas1, Gna11, Hif1a, Khsrp) were already reduced in Ngb-Tg neurons compared to WT under rest conditions. Additionally, three genes that initially showed no changes in WT neurons (Ctgf, Egfr and Peal 5) were downregulated after OGD in the Ngb-Tg neurons. These findings suggest that Ngb overexpression modulates mRNA expression of multiple hypoxic response genes in the early phase after OGD/reoxygenation. Further studies on these gene networks and interactions may lead to better understanding of Ngb in signaling pathways that contribute to neuroprotection. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Yu, Z.; Liu, J.; Guo, S.; Xing, C.; Fan, X.; Ning, M.; Yuan, J. C.; Lo, E. H.; Wang, X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Neurosci,Neuroprotect Res Lab,Dept Neurol, Charlestown, MA 02129 USA. RP Wang, X (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Neurosci,Neuroprotect Res Lab,Dept Neurol, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. EM wangxi@helix.mgh.harvard.edu FU NIH [R01-NS049476, R01-NS48422, R01-NS53560, P01-NS55104]; American Heart Association [0435087] FX This work was supported in part by a NIH grant R01-NS049476 and a Scientist Development Grant 0435087 N from American Heart Association (to X W), and NIH grants R01-NS48422, R01-NS53560, and P01-NS55104 (to E.H.L.). NR 33 TC 40 Z9 45 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD AUG 18 PY 2009 VL 162 IS 2 BP 396 EP 403 DI 10.1016/j.neuroscience.2009.04.055 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 468BE UT WOS:000267787500017 PM 19401220 ER PT J AU Kenny, EE Gusev, A Riegel, K Lutjohann, D Lowe, JK Salit, J Maller, JB Stoffel, M Daly, MJ Altshuler, DM Friedman, JM Breslow, JL Pe'er, I Sehayek, E AF Kenny, Eimear E. Gusev, Alexander Riegel, Kaitlin Luetjohann, Dieter Lowe, Jennifer K. Salit, Jacqueline Maller, Julian B. Stoffel, Markus Daly, Mark J. Altshuler, David M. Friedman, Jeffrey M. Breslow, Jan L. Pe'er, Itsik Sehayek, Ephraim TI Systematic haplotype analysis resolves a complex plasma plant sterol locus on the Micronesian Island of Kosrae SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetics; genomewide association study; haplotype mapping; plasma plant sterols ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; WHOLE-GENOME; DIETARY-CHOLESTEROL; GENETIC-VARIANTS; RISK LOCUS; POPULATION; TESTS; SUSCEPTIBILITY; TRANSPORTERS AB Pinpointing culprit causal variants along signal peaks of genomewide association studies (GWAS) is challenging. To overcome confounding effects of multiple independent variants at such a locus and narrow the interval for causal allele capture, we developed an approach that maps local shared haplotypes harboring a putative causal variant. We demonstrate our method in an extreme isolate founder population, the pacific Island of Kosrae. We analyzed plasma plant sterol (PPS) levels, a surrogate measure of cholesterol absorption from the intestine, where previous studies have implicated 2p21 mutations in the ATP binding cassette subfamily G members 5 or 8 (ABCG5 or ABCG8) genes. We have previously reported that 11.1% of the islanders are carriers of a frameshift ABCG8 mutation increasing PPS levels in carriers by 50%. GWAS adjusted for this mutation revealed genomewide significant signals along 11 Mb around it. To fine-map this signal, we detected pairwise identity-by-descent haplotypes using our tool GERMLINE and implemented a clustering algorithm to identify haplotypes shared across multiple samples with their unique shared boundaries. A single 526-kb haplotype mapped strongly to PPS levels, dramatically refining the mapped interval. This haplotype spans the ABCG5/ABCG8 genes, is carried by 1.8% of the islanders, and results in a striking 100% increase of PPS in carriers. Resequencing of ABCG5 in these carriers found a D450H missense mutation along the associated haplotype. These findings exemplify the power of haplotype analysis for mapping mutations in isolated populations and specifically for dissecting effects of multiple variants of the same locus. C1 [Kenny, Eimear E.; Lowe, Jennifer K.; Salit, Jacqueline; Friedman, Jeffrey M.; Breslow, Jan L.] Rockefeller Univ, New York, NY 10065 USA. [Kenny, Eimear E.; Gusev, Alexander; Pe'er, Itsik] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA. [Riegel, Kaitlin; Sehayek, Ephraim] Cleveland Clin, Genom Med Inst, Cleveland, OH 44195 USA. [Luetjohann, Dieter] Univ Bonn, Dept Clin Pharmacol, D-53012 Bonn, Germany. [Lowe, Jennifer K.; Maller, Julian B.; Daly, Mark J.; Altshuler, David M.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. [Lowe, Jennifer K.; Maller, Julian B.; Daly, Mark J.; Altshuler, David M.] MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Maller, Julian B.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lowe, Jennifer K.; Maller, Julian B.; Altshuler, David M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Stoffel, Markus] Swiss Fed Inst Technol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland. [Altshuler, David M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Friedman, Jeffrey M.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Breslow, JL (reprint author), Rockefeller Univ, New York, NY 10065 USA. EM breslow@rockefeller.edu RI Altshuler, David/A-4476-2009; Breslow, Jan/B-7544-2008; OI Altshuler, David/0000-0002-7250-4107; Maller, Julian/0000-0002-1565-9559 NR 57 TC 12 Z9 12 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 2009 VL 106 IS 33 BP 13886 EP 13891 DI 10.1073/pnas.0907336106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 484WE UT WOS:000269078700049 PM 19667188 ER PT J AU Guardado-Mendoza, R Davalli, AM Chavez, AO Hubbard, GB Dick, EJ Majluf-Cruz, A Tene-Perez, CE Goldschmidt, L Hart, J Perego, C Comuzzie, AG Tejero, ME Finzi, G Placidi, C La Rosa, S Capella, C Halff, G Gastaldelli, A DeFronzo, RA Folli, F AF Guardado-Mendoza, Rodolfo Davalli, Alberto M. Chavez, Alberto O. Hubbard, Gene B. Dick, Edward J. Majluf-Cruz, Abraham Tene-Perez, Carlos E. Goldschmidt, Lukasz Hart, John Perego, Carla Comuzzie, Anthony G. Tejero, Maria Elizabeth Finzi, Giovanna Placidi, Claudia La Rosa, Stefano Capella, Carlo Halff, Glenn Gastaldelli, Amalia DeFronzo, Ralph A. Folli, Franco TI Pancreatic islet amyloidosis, beta-cell apoptosis, and alpha-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amyloid deposits; non-human primates; insulin resistance; islet of Langerhans; type-2 diabetes mellitus ID ENDOPLASMIC-RETICULUM STRESS; INSULIN-RESISTANCE; ENDOCRINE-CELLS; TRANSGENIC MICE; POLYPEPTIDE; MELLITUS; GLUCOSE; INSIGHTS; EXPRESSION; IAPP AB beta-Cell dysfunction is an important factor in the development of hyperglycemia of type-2 diabetes mellitus, and pancreatic islet amyloidosis (IA) has been postulated to be one of the main contributors to impaired insulin secretion. The aim of this study was to evaluate the correlation of IA with metabolic parameters and its effect on islets of Langerhans remodeling and relative endocrine-cell volume in baboons. We sequenced the amylin peptide, determined the fibrillogenic propensities, and evaluated pancreatic histology, clinical and biochemical characteristics, and endocrine cell proliferation and apoptosis in 150 baboons with different metabolic status. Amylin sequence in the baboon was 92% similar to humans and showed superimposable fibrillogenic propensities. IA severity correlated with fasting plasma glucose (FPG) (r = 0.662, P < 0.001) and HbA1c (r = 0.726, P < 0.001), as well as with free fatty acid, glucagon values, decreased homeostasis model assessment (HOMA) insulin resistance, and HOMA-B. IA severity was associated with a decreased relative beta-cell volume, and increased relative alpha-cell volume and hyperglucagonemia. These results strongly support the concept that IA and beta-cell apoptosis in concert with alpha-cell proliferation and hypertrophy are key determinants of islets of Langerhans "dysfunctional remodeling'' and hyperglycemia in the baboon, a nonhuman primate model of type-2 diabetes mellitus. The most important determinants of IA were age and FPG (R(2) = 0.519, P < 0.0001), and different FPG levels were sensitive and specific to predict IA severity. Finally, a predictive model for islet amyloid severity was generated with age and FPG as required variables. C1 [Guardado-Mendoza, Rodolfo; Chavez, Alberto O.; Gastaldelli, Amalia; DeFronzo, Ralph A.; Folli, Franco] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Dept Med, San Antonio, TX 78229 USA. [Davalli, Alberto M.] Ist Sci San Raffaele, I-20132 Milan, Italy. [Hubbard, Gene B.; Dick, Edward J.] SW Fdn Biomed Res, San Antonio, TX 78227 USA. [Hubbard, Gene B.; Dick, Edward J.] SW Natl Primate Res Ctr, San Antonio, TX 78227 USA. [Majluf-Cruz, Abraham; Comuzzie, Anthony G.; Tejero, Maria Elizabeth] Unidad Invest Med Trombosis & Aterogenesis, Mexico City, DF, Mexico. [Tene-Perez, Carlos E.] Univ Colima, Sch Med, Colima 28040, Mexico. [Goldschmidt, Lukasz] Univ Calif Los Angeles, Dept Energy, Inst Genom & Proteom, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. [Hart, John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Hart, John] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Audie Murphy Div, Dept Vet Affairs, San Antonio, TX 78229 USA. [Perego, Carla] Univ Milan, Dept Mol Sci Appl Biosyst, I-20134 Milan, Italy. [Finzi, Giovanna; Placidi, Claudia; La Rosa, Stefano; Capella, Carlo] Univ Insubria, Dept Human Morphol, Osped Circolo, Dept Pathol, I-21100 Varese, Italy. [Finzi, Giovanna; Placidi, Claudia; La Rosa, Stefano; Capella, Carlo] Ctr Insubre Biotecnol Salute Umana, I-21100 Varese, Italy. [Halff, Glenn] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Gastaldelli, Amalia] CNR, Fdn G Monasterio, I-56126 Pisa, Italy. [Gastaldelli, Amalia] CNR, Inst Clin Physiol, I-56126 Pisa, Italy. RP Folli, F (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Dept Med, San Antonio, TX 78229 USA. EM folli@uthscsa.edu RI Gastaldelli, Amalia/H-3319-2014; Perego, Carla/L-6147-2015 OI Gastaldelli, Amalia/0000-0003-2594-1651; Perego, Carla/0000-0003-3027-1779 FU Mexican Endocrine Society/Sanofi-Aventis; Consejo Nacional de Ciencia y Tecnologia (CONACYT, Mexico); National Institutes of Health/National Center for Research Resources [P51 RR013986]; Research Facilities Improvement Program [C06 RR014578, C06 RR013556, C06 RR015456, C06 RR017515]; Robert A. Welch Foundation [AQ-1399] FX We thank Iram P. Rodriguez-Sanchez for technical help in the sequencing of IAPP, Dr. David Eisenberg (Howard Hughes Institute and University of California at Los Angeles) for critical discussion, and Dr. Leslie David Hillis for enthusiastic support and critical reading of the manuscript. This work was supported by start-up funds from the University of Texas Health Science Center (F.F.). R.G.-M. was supported by a Ralph A. DeFronzo Postdoctoral Fellowship from Mexican Endocrine Society/Sanofi-Aventis and the Consejo Nacional de Ciencia y Tecnologia (CONACYT, Mexico). This work is part of the PhD requirements for R.G.-M. at the University of Colima, Mexico, and was partially supported by the National Institutes of Health/National Center for Research Resources Grant P51 RR013986 to the Southwest National Primate Center; the investigation was conducted in part in facilities constructed with support from the Research Facilities Improvement Program under Grant numbers C06 RR014578, C06 RR013556, C06 RR015456, C06 RR017515 (to G.B.H., E.J.D., A.G.C.). J.H. was supported by Robert A. Welch Foundation Grant AQ-1399. NR 52 TC 79 Z9 79 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 2009 VL 106 IS 33 BP 13992 EP 13997 DI 10.1073/pnas.0906471106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 484WE UT WOS:000269078700067 PM 19666551 ER PT J AU Chen, ZB Carracedo, A Lin, HK Koutcher, JA Behrendt, N Egia, A Alimonti, A Carver, BS Gerald, W Teruya-Feldstein, J Loda, M Pandolfi, PP AF Chen, Zhenbang Carracedo, Arkaitz Lin, Hui-Kuan Koutcher, Jason A. Behrendt, Nille Egia, Ainara Alimonti, Andrea Carver, Brett S. Gerald, William Teruya-Feldstein, Julie Loda, Massimo Pandolfi, Pier Paolo TI Differential p53-Independent Outcomes of p19(Arf) Loss in Oncogenesis SO SCIENCE SIGNALING LA English DT Article ID ARF TUMOR-SUPPRESSOR; PROSTATE-CANCER; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; BREAST-CANCER; PTEN; P53; PATHWAY; CELLS; MDM2 AB One reported function of the tumor suppressor p19(Arf) is to stabilize p53, providing a critical checkpoint in the response to oncogenic insults. Acute loss of Pten leads to an increase in the abundance of p19(Arf), p53, and p21 proteins as part of a fail-safe senescence response. Here, we report that loss of p19(Arf) in prostate epithelium does not accelerate-but rather partially inhibits-the prostate cancer phenotype of Pten-deficient mice. Moreover, cellular senescence and a further decrease in the number of pre-neoplastic glands were observed in prostates of the Pten-p19(Arf) double-mutant mice. In both prostate epithelium and primary mouse embryo fibroblasts (MEFs), the increase in p53 protein abundance found upon loss of Pten was unaffected by the simultaneous loss of p19(Arf). However, in contrast to that in the prostate epithelium, p19(Arf) deficiency in MEFs lacking Pten abolished cell senescence and promoted hyperproliferation and transformation despite the unabated increase in p53 abundance. Consistent with the effect of p19(Arf) loss in Pten-deficient mouse prostate, we found that in human prostate cancers, loss of PTEN was not associated with loss of p14(ARF) (the human equivalent of mouse p19(Arf)). Collectively, these data reveal differential consequences of p19(Arf) inactivation in prostate cancer and MEFs upon Pten loss that are independent of the p53 pathway. C1 [Chen, Zhenbang; Carracedo, Arkaitz; Egia, Ainara; Alimonti, Andrea; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med, Beth Israel Deaconess Canc Ctr,Canc Genet Program, Boston, MA 02115 USA. [Chen, Zhenbang; Carracedo, Arkaitz; Egia, Ainara; Alimonti, Andrea; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Pathol, Beth Israel Deaconess Canc Ctr,Canc Genet Program, Boston, MA 02115 USA. [Chen, Zhenbang; Carracedo, Arkaitz; Lin, Hui-Kuan; Behrendt, Nille; Egia, Ainara; Alimonti, Andrea; Gerald, William; Teruya-Feldstein, Julie; Pandolfi, Pier Paolo] Mem Sloan Kettering Canc Ctr, Dept Pathol, Sloan Kettering Inst, New York, NY 10021 USA. [Koutcher, Jason A.] Mem Sloan Kettering Canc Ctr, Dept Med, Sloan Kettering Inst, New York, NY 10021 USA. [Koutcher, Jason A.] Mem Sloan Kettering Canc Ctr, Dept Radiol, Sloan Kettering Inst, New York, NY 10021 USA. [Koutcher, Jason A.] Mem Sloan Kettering Canc Ctr, Dept Med Phys, Sloan Kettering Inst, New York, NY 10021 USA. [Carver, Brett S.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pandolfi, PP (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med, Beth Israel Deaconess Canc Ctr,Canc Genet Program, Boston, MA 02115 USA. EM ppandolf@bidmc.harvard.edu RI Carracedo, Arkaitz/F-7029-2011; Alimonti, Andrea/J-4150-2012 OI Carracedo, Arkaitz/0000-0001-5957-1260; FU NCI NIH HHS [U01 CA-84292, R01 CA-82328, R01 CA082328, R01 CA082328-12, U01 CA084292, U01 CA084292-10, U01 CA141457, U54 CA-91408, U54 CA091408, U54 CA091408-09]; NIMHD NIH HHS [R01 MD004038] NR 34 TC 35 Z9 35 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD AUG 18 PY 2009 VL 2 IS 84 AR ra44 DI 10.1126/scisignal.2000053 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 569MS UT WOS:000275601800004 PM 19690330 ER PT J AU Walter, NAR Bottomly, D Laderas, T Mooney, MA Darakjian, P Searles, RP Harrington, CA McWeeney, SK Hitzemann, R Buck, KJ AF Walter, Nicole A. R. Bottomly, Daniel Laderas, Ted Mooney, Michael A. Darakjian, Priscila Searles, Robert P. Harrington, Christina A. McWeeney, Shannon K. Hitzemann, Robert Buck, Kari J. TI High throughput sequencing in mice: a platform comparison identifies a preponderance of cryptic SNPs SO BMC GENOMICS LA English DT Article ID MOUSE; EXPRESSION AB Background: Allelic variation is the cornerstone of genetically determined differences in gene expression, gene product structure, physiology, and behavior. However, allelic variation, particularly cryptic (unknown or not annotated) variation, is problematic for follow up analyses. Polymorphisms result in a high incidence of false positive and false negative results in hybridization based analyses and hinder the identification of the true variation underlying genetically determined differences in physiology and behavior. Given the proliferation of mouse genetic models (e. g., knockout models, selectively bred lines, heterogeneous stocks derived from standard inbred strains and wild mice) and the wealth of gene expression microarray and phenotypic studies using genetic models, the impact of naturally-occurring polymorphisms on these data is critical. With the advent of next-generation, high-throughput sequencing, we are now in a position to determine to what extent polymorphisms are currently cryptic in such models and their impact on downstream analyses. Results: We sequenced the two most commonly used inbred mouse strains, DBA/2J and C57BL/6J, across a region of chromosome 1 (171.6-174.6 megabases) using two next generation high-throughput sequencing platforms: Applied Biosystems (SOLiD) and Illumina (Genome Analyzer). Using the same templates on both platforms, we compared realignments and single nucleotide polymorphism (SNP) detection with an 80 fold average read depth across platforms and samples. While public datasets currently annotate 4,527 SNPs between the two strains in this interval, thorough high-throughput sequencing identified a total of 11,824 SNPs in the interval, including 7,663 new SNPs. Furthermore, we confirmed 40 missense SNPs and discovered 36 new missense SNPs. Conclusion: Comparisons utilizing even two of the best characterized mouse genetic models, DBA/2J and C57BL/6J, indicate that more than half of naturally-occurring SNPs remain cryptic. The magnitude of this problem is compounded when using more divergent or poorly annotated genetic models. This warrants full genomic sequencing of the mouse strains used as genetic models. C1 [Walter, Nicole A. R.; Hitzemann, Robert; Buck, Kari J.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR USA. [Walter, Nicole A. R.; Darakjian, Priscila; McWeeney, Shannon K.; Hitzemann, Robert; Buck, Kari J.] Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97201 USA. [Walter, Nicole A. R.; Darakjian, Priscila; Hitzemann, Robert; Buck, Kari J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Bottomly, Daniel; Mooney, Michael A.; McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Bottomly, Daniel; Laderas, Ted; McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97201 USA. [Laderas, Ted; Harrington, Christina A.; McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97201 USA. RP Buck, KJ (reprint author), Portland VA Med Ctr, Res & Dev Serv, Portland, OR USA. EM waltern@ohsu.edu; bottomly@ohsu.edu; laderast@ohsu.edu; mooneymi@ohsu.edu; darakjia@ohsu.edu; searlesr@ohsu.edu; harringc@ohsu.edu; mcweeney@ohsu.edu; hitzeman@ohsu.edu; buckk@ohsu.edu OI McWeeney, Shannon/0000-0001-8333-6607; Laderas, Ted/0000-0002-6207-7068; Mooney, Michael/0000-0003-1372-8722 FU [5R01AA011114]; [5R01DA005228]; [5P60AA10760]; [5R01AA11034]; [5R01AA13484]; [5T15LM007088]; [5P30CA069533]; [UL1RR024140] FX This work is supported by 5R01AA011114, 5R01DA005228, 5P60AA10760, 5R01AA11034, 5R01AA13484, 5T15LM007088, 5P30CA069533, UL1RR024140, and the VA. We thank Illumina and Applied Biosystems for their assistance in the generation and realignment of these sequencing data. NR 22 TC 18 Z9 19 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD AUG 17 PY 2009 VL 10 AR 379 DI 10.1186/1471-2164-10-379 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 501PI UT WOS:000270393400001 PM 19686600 ER PT J AU Kang, D Yelin, D Bouma, BE Tearney, GJ AF Kang, DongKyun Yelin, Dvir Bouma, Brett E. Tearney, Guillermo J. TI Spectrally-encoded color imaging SO OPTICS EXPRESS LA English DT Article ID MINIATURE ENDOSCOPY; FIBER AB Spectrally-encoded endoscopy (SEE) is a technique for ultraminiature endoscopy that encodes each spatial location on the sample with a different wavelength. One limitation of previous incarnations of SEE is that it inherently creates monochromatic images, since the spectral bandwidth is expended in the spatial encoding process. Here we present a spectrally-encoded imaging system that has color imaging capability. The new imaging system utilizes three distinct red, green, and blue spectral bands that are configured to illuminate the grating at different incident angles. By careful selection of the incident angles, the three spectral bands can be made to overlap on the sample. To demonstrate the method, a bench-top system was built, comprising a 2400-lpmm grating illuminated by three 525-mu m-diameter beams with three different spectral bands. Each spectral band had a bandwidth of 75 nm, producing 189 resolvable points. A resolution target, color phantoms, and excised swine small intestine were imaged to validate the system's performance. The color SEE system showed qualitatively and quantitatively similar color imaging performance to that of a conventional digital camera. (C) 2009 Optical Society of America C1 [Kang, DongKyun; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kang, DongKyun; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Yelin, Dvir] Technion Israel Inst Technol, Dept Biomed Engn, IL-32000 Haifa, Israel. RP Kang, D (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM gtearney@partners.org RI Kang, Dongkyun/C-1085-2013 OI Kang, Dongkyun/0000-0001-5063-5387 FU National Institute of Health/National Institute of Biomedical Imaging and Bioengineering [R21EB007718] FX This research was sponsored by National Institute of Health/National Institute of Biomedical Imaging and Bioengineering (Grant #R21EB007718). NR 19 TC 10 Z9 12 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD AUG 17 PY 2009 VL 17 IS 17 BP 15239 EP 15247 DI 10.1364/OE.17.015239 PG 9 WC Optics SC Optics GA 486XA UT WOS:000269232800079 PM 19688002 ER PT J AU Zhang, Y Zhang, Y AF Zhang, Yu Zhang, Ying TI Natural enrichment of foods through bacterial fermentation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zhang, Yu] Massachusetts Gen Hosp, Brookline, MA 02445 USA. [Zhang, Yu] Harvard Univ, Sch Med, Brookline, MA 02445 USA. [Zhang, Ying] Zhejiang Univ, Dept Food Sci & Nutr, Hangzhou 310029, Zhejiang, Peoples R China. EM y_zhang@zju.edu.cn; y_zhang@zju.edu.cn NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 34-AGFD BP 362 EP 362 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861900322 ER PT J AU Kim, YW Kutchukian, PS Crenshaw, CM Stanton, SS Chang, A Verdine, GL AF Kim, Young-Woo Kutchukian, Peter S. Crenshaw, Charisse M. Stanton, Shaunna S. Chang, Andrew Verdine, Gregory L. TI Peptide stitching: A powerful tool for alpha-helix stabilization SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Verdine, Gregory L.] Harvard Univ, Dana Farber Canc Inst, Program Canc Chem Biol, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. EM Young-Woo_Kim@dfci.harvard.edu; kutchuk@fas.harvard.edu; crenshaw@fas.harvard.edu; stanton2@fas.harvard.edu; andrew.chang@post.harvard.edu; gregory_verdine@harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 20-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907189 ER PT J AU Huett, A Xavier, R AF Huett, Alan Xavier, Ramnik TI Building complex biological networks based upon model organisms Mapping the human autophagy interactome via a hybrid yeast-human protein interaction network SO AUTOPHAGY LA English DT Editorial Material DE systems biology; network biology; evolution; xenophagy; membrane C1 [Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol,Simches Res Ctr, Boston, MA 02114 USA. [Huett, Alan; Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Ctr Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Xavier, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol,Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu NR 0 TC 2 Z9 2 U1 1 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD AUG 16 PY 2009 VL 5 IS 6 BP 884 EP 886 DI 10.4049/jimmunol.0803050 PG 3 WC Cell Biology SC Cell Biology GA 484CU UT WOS:000269021700027 PM 19535904 ER PT J AU Xavier, R AF Xavier, Ramnik TI Building biological networks in autophagy SO AUTOPHAGY LA English DT Meeting Abstract DE Crohn disease; integrative genomics; ATG16L1; bacterial effectors; human genetics C1 [Xavier, Ramnik] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Program Med & Populat Gene, Ctr Computat & Integrat Biol,Broad Inst MIT & Har, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD AUG 16 PY 2009 VL 5 IS 6 BP 908 EP 908 PG 1 WC Cell Biology SC Cell Biology GA 484CU UT WOS:000269021700070 ER PT J AU Pride, YB Appelbaum, E Lord, EE Sloan, S Cannon, CP Sabatine, MS Gibson, CM AF Pride, Yuri B. Appelbaum, Evan Lord, Erin E. Sloan, Sarah Cannon, Christopher P. Sabatine, Marc S. Gibson, C. Michael CA TIMI Study Grp TI Relation Between Myocardial Infarct Size and Ventricular Tachyarrhythmia Among Patients With Preserved Left Ventricular Ejection Fraction Following Fibrinolytic Therapy for ST-Segment Elevation Myocardial Infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CREATINE-PHOSPHOKINASE ACTIVITY; CK-MB; RADIONUCLIDE VENTRICULOGRAPHY; PROGNOSTIC-SIGNIFICANCE; HEART-FAILURE; KINASE-MB; DEFIBRILLATOR; CLOPIDOGREL; SEVERITY; TRENDS AB In the era of early reperfusion therapy for ST-segment elevation myocardial infarction, preserved left ventricular (LV) function is common. Despite preservation of LV ejection fraction (LVEF), there remains a spectrum of risk for adverse cardiovascular events, including ventricular tachycardia (VT) and ventricular fibrillation (VF). Larger infarct size has been independently associated with death, VT/VF, and heart failure in the post-myocardial infarction population. It was hypothesized that infarct size, as estimated by peak serum creatine kinase (CK)-MB concentration, would be associated with the incidence of VT/VF in patients with preserved LV function after ST-segment elevation myocardial infarctions. The Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28 (CLARITY-TIMI 28) study enrolled 3,491 patients with ST-segment elevation myocardial infarctions who underwent fibrinolytic therapy. The association between estimated infarct size (ratio of peak CK-MB to the upper limit of normal), the LVEF (measured using left ventriculography or echocardiography), and the incidence of VT/VF through 30 days was assessed. A total of 1,436 patients underwent assessments of LV function, of whom 1,133 had adequate CK-MB for analysis. The median LVEF in this group was 55% (interquartile range 45% to 65%), and most patients (n = 814 [87.1%]) had LVEF >= 40%. Among patients with LVEF >= 40%, the ratio of peak CK-MB to the upper limit of normal was significantly associated with the incidence of VT/VF through 30 days (2.2%, 3.7%, and 5.5% across tertiles, respectively, p = 0.041 for trend) and the incidence of the composite of cardiovascular death, heart failure, shock, and VT/VF through 30 days (3.7%, 6.0%, 8.5%, respectively, p = 0.018 for trend). In conclusion, in patients with ST-segment elevation myocardial infarction with preserved LV function after reperfusion therapy, larger infarct size, as estimated by peak serum CK-MB concentration, is significantly associated with VT/VF as well as other adverse clinical outcomes. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:475-479) C1 [Appelbaum, Evan; Gibson, C. Michael] Harvard Univ, Sch Med, Div Cardiol, Boston, MA 02115 USA. [Pride, Yuri B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lord, Erin E.; Sloan, Sarah; Gibson, C. Michael] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, TIMI Study Grp, Boston, MA 02215 USA. [Cannon, Christopher P.; Sabatine, Marc S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. RP Gibson, CM (reprint author), Harvard Univ, Sch Med, Div Cardiol, Boston, MA 02115 USA. EM mgibson@perfuse.org FU Sanofi-Aventis, Paris, France; Bristol-Myers Squibb, Princeton, New Jersey FX The CLARITY-TIMI 28 study was supported by a grant from Sanofi-Aventis, Paris, France, and Bristol-Myers Squibb, Princeton, New Jersey. NR 29 TC 12 Z9 12 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 2009 VL 104 IS 4 BP 475 EP 479 DI 10.1016/j.amjcard.2009.04.005 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 488TJ UT WOS:000269372700004 PM 19660597 ER PT J AU Fox, CS Hwang, SJ Massaro, JM Lieb, K Vasan, RS O'Donnell, CJ Hoffmann, U AF Fox, Caroline S. Hwang, Shih-Jen Massaro, Joseph M. Lieb, Kathrin Vasan, Ramachandran S. O'Donnell, Christopher J. Hoffmann, Udo TI Relation of Subcutaneous and Visceral Adipose Tissue to Coronary and Abdominal Aortic Calcium (from the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; ARTERY CALCIUM; RISK-FACTORS; CARDIOVASCULAR-DISEASE; YOUNG-ADULTS; FOLLOW-UP; CALCIFICATION; OBESITY; PROGRESSION; COMMUNITY AB Body fat distribution might be differentially associated with subclinical cardiovascular disease. We examined whether the body mass index, waist circumference, and subcutaneous and visceral adipose tissue are associated with the prevalence of either coronary or abdominal aortic calcium in the Framingham Heart Study. Participants (n = 3,130, mean age 52 years, 49% women) free of clinical cardiovascular disease from the Framingham Heart Study underwent multidetector computed tomographic assessment to quantify the subcutaneous and visceral fat volume and coronary and abdominal aortic calcification. Coronary artery calcification and abdominal aortic calcium were examined in relation to the body mass index, waist circumference, subcutaneous adipose tissue, and visceral adipose tissue in age-, gender-, and multivariate-adjusted models. All measures of adiposity were associated with coronary aortic calcium in the age- and gender-adjusted models (all p <0.008). All relations were attenuated in the multivariate models (all p >0.14). The body mass index, waist circumference, and visceral adipose tissue (but not the subcutaneous adipose tissue) were associated with abdominal aortic calcification in the age- and gender-adjusted models (all p <0.012). However, all relations were attenuated in the multivariate models (all p >0.23). Similar findings were observed in the quartile-based analyses. In conclusion, the general measures of obesity and measures of central abdominal fat are related to the coronary aortic calcium and abdominal aortic calcium levels. However, these cross-sectional associations are attenuated by cardiovascular disease risk factors, possibly because they mediate the association between adiposity measures and subclinical cardiovascular disease. Published by Elsevier Inc. (Am J Cardiol 2009;104:543-547) C1 [Fox, Caroline S.; Hwang, Shih-Jen; Lieb, Kathrin; Vasan, Ramachandran S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [O'Donnell, Christopher J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Massaro, Joseph M.] Sch Publ Hlth, Div Biostat, Boston, MA USA. [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA 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's Framingham Heart Study, Bethesda, Maryland [N01-HC-25195]; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland [2K24HL04334, R01-DK-080739] FX This work was supported by Grant N01-HC-25195 from the National Heart, Lung and Blood Institute's Framingham Heart Study, Bethesda, Maryland. Dr. Vasan was supported in part by Grants 2K24HL04334 and R01-DK-080739 from the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. NR 21 TC 27 Z9 30 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 2009 VL 104 IS 4 BP 543 EP 547 DI 10.1016/j.amjcard.2009.04.019 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 488TJ UT WOS:000269372700016 PM 19660609 ER PT J AU Maguire, CA Deliolanis, NC Pike, L Niers, JM Tjon-Kon-Fat, LA Sena-Esteves, M Tannous, BA AF Maguire, Casey A. Deliolanis, Nikolaos C. Pike, Lisa Niers, Johanna M. Tjon-Kon-Fat, Lee-Ann Sena-Esteves, Miguel Tannous, Bakhos A. TI Gaussia Luciferase Variant for High-Throughput Functional Screening Applications SO ANALYTICAL CHEMISTRY LA English DT Article ID IN-VIVO; BIOLOGICAL PROCESSES; SECRETORY PATHWAY; GENE-EXPRESSION; CELLS; REPORTER; PRINCEPS; CULTURE; LIGHT; ASSAY AB Gaussia luciferase (Glue) is a sensitive reporter for studying different biological processes such as gene expression, promoter activity, protein-protein interactions, signal transduction, as well as tumor cell growth and response to therapy. Since Glue is naturally secreted, the kinetics of these processes can be monitored in real-time by measuring an aliquot of conditioned medium in culture or a few microliters of blood in vivo at different time points. Glue catalyzes light emission with a short half-life which is unfavorable for certain applications. We isolated a Glue mutant that catalyzes enhanced light stability in the presence of a detergent, in combination with high sensitivity, making it an attractive luciferase for high-throughput functional screening applications. C1 [Maguire, Casey A.; Deliolanis, Nikolaos C.; Pike, Lisa; Niers, Johanna M.; Tjon-Kon-Fat, Lee-Ann; Sena-Esteves, Miguel; Tannous, Bakhos A.] Harvard Univ, Sch Med, Mol Neurogenet Unit, Dept Neurol, Boston, MA 02115 USA. [Maguire, Casey A.; Deliolanis, Nikolaos C.; Sena-Esteves, Miguel; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Deliolanis, Nikolaos C.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02115 USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, 149 13th St,Room 6101, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu OI Deliolanis, Nikolaos/0000-0002-6392-3035 FU NIH/NINDS [1R21NS061051]; NIH [5 T32 CA073479-09] FX This work was supported in parts by grants from the NIH/NINDS (Grant 1R21NS061051 to B.A.T.) and NIH (Grant 5 T32 CA073479-09 to C.A.M.). We thank Dr. Rakesh Jain for support during this study and Dr. R. Weissleder. Director of the Center for Molecular Imaging Research at the Massachusetts General Hospital, for the use of the CCD camera. NR 21 TC 40 Z9 41 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD AUG 15 PY 2009 VL 81 IS 16 BP 7102 EP 7106 DI 10.1021/ac901234r PG 5 WC Chemistry, Analytical SC Chemistry GA 482RW UT WOS:000268907400069 PM 19601604 ER PT J AU Cooley, M Pless, M Stone, JH AF Cooley, Michael Pless, Misha Stone, John H. TI A 58-Year-Old Woman With a Droopy Left Eye and Vision Loss SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID WEGENERS-GRANULOMATOSIS; MENINGEAL INVOLVEMENT; OPTIC NEUROPATHY; MANIFESTATIONS; VASCULITIS; RITUXIMAB; DEPLETION; THERAPY C1 [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St Yawkey 2, Boston, MA 02114 USA. EM jhstone@partners.org NR 24 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD AUG 15 PY 2009 VL 61 IS 8 BP 1133 EP 1139 DI 10.1002/art.24605 PG 7 WC Rheumatology SC Rheumatology GA 485PH UT WOS:000269135300018 PM 19644910 ER PT J AU DeLuca, DS Beisswanger, E Wermter, J Horn, PA Hahn, U Blasczyk, R AF DeLuca, David S. Beisswanger, Elena Wermter, Joachim Horn, Peter A. Hahn, Udo Blasczyk, Rainer TI MaHCO: an ontology of the major histocompatibility complex for immunoinformatic applications and text mining SO BIOINFORMATICS LA English DT Article ID HLA-DR; DATABASE; ANTIGENS; PREDICTION; SYSTEM; TOOL; DQ AB Motivation: The high level of polymorphism associated with the major histocompatibility complex (MHC) poses a challenge to organizing associated bioinformatic data, particularly in the area of hematopoietic stem cell transplantation. Thus, this area of research has great potential to profit from the ongoing development of biomedical ontologies, which offer structure and definition to MHC-data related communication and portability issues. Results: We introduce the design considerations, methodological foundations and implementational issues underlying MaHCO, an ontology which represents the alleles and encoded molecules of the major histocompatibility complex. Importantly for human immunogenetics, it includes a detailed level of human leukocyte antigen (HLA) classification. We then present an ontology browser, search interfaces for immunogenetic fact and document retrieval, and the specification of an annotation language for semantic metadata, based on MaHCO. These use cases are intended to demonstrate the utility of ontology-driven bioinformatics in the field of immunogenetics. C1 [DeLuca, David S.; Blasczyk, Rainer] Hannover Med Sch, Inst Transfus Med, D-3000 Hannover, Germany. [DeLuca, David S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Beisswanger, Elena; Wermter, Joachim; Hahn, Udo] Univ Jena, Language & Informat JULIE Lab, Jena, Germany. [Horn, Peter A.] Univ Hosp Essen, Inst Transfus Med, Essen, Germany. RP DeLuca, DS (reprint author), Hannover Med Sch, Inst Transfus Med, D-3000 Hannover, Germany. EM david_deluca@dfci.harvard.edu FU German Federal Ministry of Education and Research [01DS001A-1C] FX German Federal Ministry of Education and Research, grant number 01DS001A-1C. NR 32 TC 4 Z9 4 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD AUG 15 PY 2009 VL 25 IS 16 BP 2064 EP 2070 DI 10.1093/bioinformatics/btp306 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 481KJ UT WOS:000268808600010 PM 19429601 ER PT J AU Morgan, CA Rasmusson, A Pietrzak, RH Coric, V Southwick, SM AF Morgan, Charles A., III Rasmusson, Ann Pietrzak, Robert H. Coric, Vladimir Southwick, Steven M. TI Relationships Among Plasma Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate, Cortisol, Symptoms of Dissociation, and Objective Performance in Humans Exposed to Underwater Navigation Stress SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Cognitive; hormones; military; performance; special forces; stress ID PREFRONTAL CORTEX; SPATIAL MEMORY; SALIVARY CORTISOL; HUMAN HIPPOCAMPUS; MAJOR DEPRESSION; EPISODIC MEMORY; DHEA; MEN; CORTICOSTERONE; RECEPTOR AB Background: A growing body of research has provided evidence that dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are involved in an organism's response to stress and that it may provide beneficial behavioral and neurotrophic effects. Methods: This study investigated plasma DHEA and DHEAS, cortisol, psychological symptoms of dissociation, and military performance in 41 healthy active duty subjects enrolled in the military Combat Diver Qualification Course (CDQC). Results: Baseline values of DHEA and DHEAS were significantly and positively predictive of superior performance in the underwater navigation exam; in addition, DHEA and DHEAS were significantly and negatively related to stress-induced symptoms of dissociation during performance of the task. Similarly, participants who reported fewer symptoms of dissociation exhibited superior military performance and increased levels of DHEA after the test. Conclusions: These data provide prospective, empiric evidence that DHEA and DHEAS are associated with superior stress tolerance, fewer symptoms of dissociation, and superior, objectively assessed, military performance. C1 [Morgan, Charles A., III; Pietrzak, Robert H.; Southwick, Steven M.] VA Connecticut Healthcare Syst, Natl Ctr PTSD, West Haven, CT 06516 USA. [Rasmusson, Ann] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Rasmusson, Ann] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Morgan, Charles A., III; Pietrzak, Robert H.; Coric, Vladimir; Southwick, Steven M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Morgan, CA (reprint author), VA Connecticut Healthcare Syst, Natl Ctr PTSD, C-O 116A,950 Campbell Ave, West Haven, CT 06516 USA. EM charles.a.morgan@yale.edu NR 56 TC 43 Z9 43 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 2009 VL 66 IS 4 BP 334 EP 340 DI 10.1016/j.biopsych.2009.04.004 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 481VL UT WOS:000268840200007 PM 19500775 ER PT J AU Hattangadi, JA Hong, TS Yeap, BY Mamon, HJ AF Hattangadi, Jona A. Hong, Theodore S. Yeap, Beow Y. Mamon, Harvey J. TI Results and Patterns of Failure in Patients Treated With Adjuvant Combined Chemoradiation Therapy for Resected Pancreatic Adenocarcinoma SO CANCER LA English DT Article DE pancreatic cancer; adjuvant therapy; chemoradiation; gemcitabine; patterns of failure ID RANDOMIZED CONTROLLED-TRIAL; CANCER COOPERATIVE GROUP; PHASE-III TRIAL; CURATIVE RESECTION; DUCTAL ADENOCARCINOMA; PERIAMPULLARY REGION; CHEMOTHERAPY; 5-FLUOROURACIL; RADIOTHERAPY; RADIATION AB BACKGROUND: Although adjuvant chemoradiation is used commonly in the United States for the treatment of resected pancreatic cancer, there is no consensus on the benefit of this therapy, because the results from randomized trials are conflicting. The authors of this report reviewed their experience in a consecutive, unselected series of patients who received adjuvant 5-fluorouracil (5-FU) and radiation therapy (RT) for resected pancreatic adenocarcinoma. METHODS: Eighty-six patients with resected pancreatic adenocarcinoma who received adjuvant therapy from 1998 to 2005 were identified, and their medical records were reviewed. Ninety-three percent of patients were treated with external beam RT to >= 50.4 grays, and 91% of patients received concurrent 5-FU by continuous infusion. Forty-five percent of patients went on to receive adjuvant gemcitabine. RESULTS: The median follow-up was 31 months (range, 21-62 months) among the 20 patients who remained alive. Less than half of patients had positive (33%) or close (<1 mm; 15%) resection margins, 81% of tumors were classified as T3, and 66% of patients had involved lymph nodes. The median overall survival (OS) for all patients was 22 months. Negative lymph node status (P = .016) was a significant prognostic factor for improved OS, whereas treatment with gemcitabine trended toward improved OS (P = .080). The median disease-free survival (DFS) for all patients was 10 months: Treatment with gemcitabine (P = .044) and the receipt of any chemotherapy (P = .047) were significant predictors of DFS. Seventy-five patients (87%) had disease recurrence, and the majority recurred with peritoneal metastases (55%) or liver metastases (53%). Patients who had negative lymph nodes trended toward a lower rate of distant failure (P = .060). CONCLUSIONS: The median survival of the current cohort was greater than that of the chemoradiation arms of European Organization for Research and Treatment of Cancer trials and European Study Group for Pancreatic Cancer I trials and was comparable to the survival observed on the Gastrointestinal Tumor Study Group chemoradiation arm. Lymph node status and treatment with adjuvant chemotherapy were significant predictors of OS and DFS, respectively. Future survival improvements should be directed at reducing peritoneal and liver metastases. Further randomized trials will be required to define the role of adjuvant therapy for pancreatic adenocarcinoma. Cancer 2009;115:3640-50. (C) 2009 American Cancer Society. C1 [Hattangadi, Jona A.; Mamon, Harvey J.] Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Sch Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [Hattangadi, Jona A.; Hong, Theodore S.] Harvard Univ, Dept Radiat Oncol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Yeap, Beow Y.] Harvard Univ, Dept Med, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Mamon, HJ (reprint author), Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Sch Med,Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM hmamon@lroc.harvard.edu FU Dana-Farber/Harvard Cancer Center Cancer Core [P30 CA06516] FX Supported by Dana-Farber/Harvard Cancer Center Cancer Core Support Grant P30 CA06516. NR 28 TC 27 Z9 29 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2009 VL 115 IS 16 BP 3640 EP 3650 DI 10.1002/cncr.24410 PG 11 WC Oncology SC Oncology GA 481DH UT WOS:000268786800008 PM 19514088 ER PT J AU Grandinetti, KB Jelinic, P DiMauro, T Pellegrino, J Rodriguez, RF Finnerty, PM Ruoff, R Bardeesy, N Logan, SK David, G AF Grandinetti, Kathryn B. Jelinic, Petar DiMauro, Teresa Pellegrino, Jessica Rodriguez, Ruben Fernandez Finnerty, Patricia M. Ruoff, Rachel Bardeesy, Nabeel Logan, Susan K. David, Gregory TI Sin3B Expression Is Required for Cellular Senescence and Is Up-regulated upon Oncogenic Stress SO CANCER RESEARCH LA English DT Article ID PANCREATIC INTRAEPITHELIAL NEOPLASIA; TUMOR-SUPPRESSOR; DNA-DAMAGE; HETEROCHROMATIN FORMATION; E2F; P16(INK4A); CELLS; MICE; P53; TUMORIGENESIS AB Serial passage of primary mammalian cells or strong mitogenic signals induce a permanent exit from the cell cycle called senescence. A characteristic of senescent cells is the hetero-chromatinization of loci encoding pro-proliferative genes, leading to their transcriptional silencing. Senescence is thought to represent a defense mechanism against uncontrolled proliferation and cancer. Consequently, genetic alterations that allow senescence bypass are associated with susceptibility to oncogenic transformation. We show that fibroblasts genetically inactivated for the chromatin-associated Sin3B protein are refractory to replicative and oncogene-induced senescence. Conversely, overexpression of Sin3B triggers senescence and the formation of senescence-associated heterochromatic foci. Although Sin3B is strongly up-regulated upon oncogenic stress, decrease in expression of Sin3B is associated with tumor progression in vivo, suggesting that expression of Sin3B may represent a barrier against transformation. Together, these results underscore the contribution of senescence in tumor suppression and suggest that expression of chromatin modifiers is modulated at specific stages of cellular transformation. Consequently, these findings suggest that modulation of Sin3B-associated activities may represent new therapeutic opportunities for treatment of cancers. [Cancer Res 2009;(69(16):6430-7] C1 [Grandinetti, Kathryn B.; Jelinic, Petar; DiMauro, Teresa; Pellegrino, Jessica; Rodriguez, Ruben Fernandez; Finnerty, Patricia M.; Ruoff, Rachel; Logan, Susan K.; David, Gregory] NYU, Dept Pharmacol, Langone Med Ctr, New York, NY 10016 USA. [Ruoff, Rachel; Logan, Susan K.] NYU, Dept Urol, Langone Med Ctr, New York, NY 10016 USA. [Ruoff, Rachel; Logan, Susan K.; David, Gregory] NYU, Inst Canc, Langone Med Ctr, New York, NY 10016 USA. [Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP David, G (reprint author), NYU, Dept Pharmacol, Langone Med Ctr, MSB417,550 1St Ave, New York, NY 10016 USA. EM gregory.david@nyumc.org RI Ruoff, Rodney/B-7605-2009; OI , gregory/0000-0002-3371-4558 FU Brit Syndrome Research Foundation; March of Dimes; American Federation for Aging Research; American Cancer Society; NIH [CA112226, CA009161] FX Brit Syndrome Research Foundation (G. David), March of Dimes (G. David), the American Federation for Aging Research (G. David), American Cancer Society (G. David and K.B. Grandinetti). NIH grant CA112226 (S.K. Logan), and NIH training grant CA009161 (K.B. Grandinetti). NR 42 TC 21 Z9 21 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2009 VL 69 IS 16 BP 6430 EP 6437 DI 10.1158/0008-5472.CAN-09-0537 PG 8 WC Oncology SC Oncology GA 484RI UT WOS:000269064600010 PM 19654306 ER PT J AU Jagani, Z Song, KL Kutok, JL Dewar, MR Melet, A Santos, T Grassian, A Ghaffari, S Wu, C Ren, RB Rodin, HY Miller, K Khosravi-Far, R AF Jagani, Zainab Song, Keli Kutok, Jeffery L. Dewar, M. Rajan Melet, Armelle Santos, Tanya Grassian, Alexandra Ghaffari, Saghi Wu, Catherine Ren, Ruibao Rodin, Heather Yeckes Miller, Kenneth Khosravi-Far, Roya TI Proteasome Inhibition Causes Regression of Leukemia and Abrogates BCR-ABL-Induced Evasion of Apoptosis in Part through Regulation of Forkhead Tumor Suppressors SO CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; FOXO TRANSCRIPTION FACTORS; TYROSINE KINASE INHIBITOR; HEMATOPOIETIC-CELLS; MULTIPLE-MYELOMA; PHOSPHATIDYLINOSITOL 3-KINASE; PHILADELPHIA-CHROMOSOME; CANCER-THERAPY; RESISTANCE AB BCR-ABL plays an essential role in the pathogenesis of chronic myeloid leukemia (CML) and some cases of acute lymphocytic leukemia (ALL). Although ABL kinase inhibitors have shown great promise in the treatment of CML, the persistence of residual disease and the occurrence of resistance have prompted investigations into the molecular effectors of BCR-ABL. Here, we show that BCR-ABL stimulates the proteasome-dependent degradation of members of the forkhead family of tumor suppressors in vitro, in an in vivo animal model, and in samples from patients with BCR-ABL-positive CML or ALL. As several downstream mediators of BCR-ABL are regulated by the proteasome degradation pathway, we also show that inhibition of this pathway, using bortezomib, causes regression of CML-like disease. Bortezomib treatment led to inhibition of BCR-ARL-induced suppression of FoxO proteins and their proapoptotic targets, tumor necrosis factor-related apoptosis-inducing ligand and BIM, thereby providing novel insights into the molecular effects of proteasome inhibitor therapy. We additionally show sensitivity of imatinib-resistant BCR-ABL T3151 cells to bortezomib. Our data delineate the involvement of FoxO proteins in BCR-ABL-induced evasion of apoptosis and provide evidence that bortezomib is a candidate therapeutic in the treatment of BCR-ARL-induced leukemia. [Cancer Res 2009;69(16):6546-55] C1 [Jagani, Zainab; Song, Keli; Dewar, M. Rajan; Melet, Armelle; Santos, Tanya; Grassian, Alexandra; Khosravi-Far, Roya] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Jagani, Zainab; Song, Keli; Dewar, M. Rajan; Melet, Armelle; Santos, Tanya; Grassian, Alexandra; Khosravi-Far, Roya] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Jagani, Zainab; Khosravi-Far, Roya] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA 02215 USA. [Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wu, Catherine] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Rodin, Heather Yeckes; Miller, Kenneth] Tufts Med Ctr, Boston, MA USA. [Ghaffari, Saghi] Mt Sinai Sch Med, New York, NY USA. [Ren, Ruibao] Brandeis Univ, Dept Biol, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02254 USA. RP Khosravi-Far, R (reprint author), Harvard Univ, Sch Med, Dept Pathol, 3 Blackfan Circle, Boston, MA 02215 USA. EM rkhosrav@bidmc.harvard.edu FU NIH [CA105306, CA131664, HL080192, P30CA6516]; Millennium Pharmaceuticals; Specialized Histopathology Core Lab of the Dana-Farber/Harvard Cancer Center FX NIH grants CA105306. CA131664, and HL080192 and Millennium Pharmaceuticals investigator-initiated grant (B. Khosravi-Far). It. Khosravi-Far is an American Cancer Society Scholar. Immunohistochemical methodology was supported by the Specialized Histopathology Core Lab of the Dana-Farber/Harvard Cancer Center (NIH grant P30CA6516). NR 50 TC 29 Z9 31 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2009 VL 69 IS 16 BP 6546 EP 6555 DI 10.1158/0008-5472.CAN-09-0605 PG 10 WC Oncology SC Oncology GA 484RI UT WOS:000269064600024 PM 19654305 ER PT J AU Schittenhelm, MM Kampa, KM Yee, KWH Heinrich, MC AF Schittenhelm, Marcus M. Kampa, Kerstin M. Yee, Kevin W. H. Heinrich, Michael C. TI The FLT3 inhibitor tandutinib (formerly MLN518) has sequence-independent synergistic effects with cytarabine and daunorubicin SO CELL CYCLE LA English DT Article DE AML; FLT3 ITD; tandutinib; synergy; chemotherapy ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; WILD-TYPE; IN-VITRO; MYELODYSPLASTIC SYNDROME; CONSTITUTIVE ACTIVATION; LESTAURTINIB CEP701; POOR-PROGNOSIS AB AML remains a difficult disease to treat. Despite response to induction chemotherapy, most patients ultimately relapse. Further, among elderly patients, aggressive therapy options are often limited due to other medical conditions and decreased tolerance of these patients to conventional chemotherapy. Internal tandem duplications (ITD) of the FLT3 juxtamembrane domain occur in 20-30% of AML patients and predict poor outcome. First clinical data with the FLT3 inhibitor tandutinib demonstrated antileukemic activity in approximately half of the patients-predominantly with FLT3 ITD positive AML. But the data also show that optimal use of tandutinib will require combination therapy with cytotoxic agents. Notably, single agent tandutinib has not been associated with myelosuppression, mucositis or cardiac toxicity-the dose limiting toxicities of AML chemotherapy. We determined the feasibility of combining tandutinib with the standard "3 + 7" induction regimen in AML and show that, in contrast to other structurally unrelated FLT3 inhibitors recently evaluated in clinical trials, the use of tandutinib displayed application sequence independent synergistic antileukemic effects in combination with cytarabine and daunorubicin. Strong synergistic antiproliferative and proapoptotic effects were thereby predominantly seen on FLT3 ITD positive blasts. Further we demonstrate, that addition of tandutinib may allow dose reduction of chemotherapy without loss of overall antileukemic activity-resulting in a potential decrease of side effects. This approach might be an interesting novel strategy especially in the treatment of elderly/comorbid patients. Our data provide a rationale for combining tandutinib with induction chemotherapy in intensified as well as in dose reduction protocols for FLT3 ITD positive AML. C1 [Schittenhelm, Marcus M.; Kampa, Kerstin M.] Univ Tubingen, Med Univ Klin, Dept Hematol Oncol Rheumatol Immunol & Pulmol, Tubingen, Germany. [Schittenhelm, Marcus M.; Kampa, Kerstin M.; Yee, Kevin W. H.; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Dept Med, Portland VA Med Ctr, Knight Canc Inst, Portland, OR 97201 USA. [Schittenhelm, Marcus M.; Kampa, Kerstin M.; Yee, Kevin W. H.; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland VA Med Ctr, Knight Canc Inst, Portland, OR 97201 USA. [Schittenhelm, Marcus M.; Kampa, Kerstin M.; Yee, Kevin W. H.; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Div Hematol Oncol, Knight Canc Inst, Portland, OR 97201 USA. [Schittenhelm, Marcus M.; Kampa, Kerstin M.; Yee, Kevin W. H.; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Dept Med, Div Hematol Oncol, Knight Canc Inst, Portland, OR 97201 USA. RP Schittenhelm, MM (reprint author), Otfried Mueller Str 10, D-72076 Tubingen, Germany. EM marcus.schittenhelm@med.uni-tuebingen.de FU Department of Veterans Affairs; Doris Duke Charitable Foundation; Leukemia and Lymphoma Society; Deutsche Krebshilfe Foundation; Tubingen Medical School [F14900-0] FX We thank the core facilities of the OHSU Cancer Institute and Mrs. Alida Theil at the Medizinische Universitatsklinik Tubingen for excellent technical assistance.; Supported in part by a Merit Review Grant from the Department of Veterans Affairs (MCH), and grants from the Doris Duke Charitable Foundation (MCH), the Leukemia and Lymphoma Society (MCH), the Deutsche Krebshilfe Foundation (MMS) and Fortune-Program of the Tubingen Medical School (Nr. F14900-0; MMS). NR 40 TC 17 Z9 19 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD AUG 15 PY 2009 VL 8 IS 16 BP 2621 EP 2630 DI 10.4161/cc.8.16.9355 PG 10 WC Cell Biology SC Cell Biology GA 483QY UT WOS:000268983900030 PM 19625780 ER PT J AU Evans, DG Kalamarides, M Hunter-Schaedle, K Blakeley, J Allen, J Babovic-Vuskanovic, D Belzberg, A Bollag, G Chen, RH DiTomaso, E Golfinos, J Harris, G Jacob, A Kalpana, G Karajannis, M Korf, B Kurzrock, R Law, M McClatchey, A Packer, R Roehm, P Rubenstein, A Slattery, W Tonsgard, JH Welling, DB Widemann, B Yohay, K Giovannini, M AF Evans, D. Gareth Kalamarides, Michel Hunter-Schaedle, Kim Blakeley, Jaishri Allen, Jeffrey Babovic-Vuskanovic, Dusica Belzberg, Allan Bollag, Gideon Chen, Ruihong DiTomaso, Emmanuelle Golfinos, John Harris, Gordon Jacob, Abraham Kalpana, Ganjam Karajannis, Matthias Korf, Bruce Kurzrock, Razelle Law, Meng McClatchey, Andrea Packer, Roger Roehm, Pamela Rubenstein, Allan Slattery, William, III Tonsgard, James H. Welling, D. Bradley Widemann, Brigitte Yohay, Kaleb Giovannini, Marco TI Consensus Recommendations to Accelerate Clinical Trials for Neurofibromatosis Type 2 SO CLINICAL CANCER RESEARCH LA English DT Article ID VESTIBULAR-SCHWANNOMA; MENINGIOMA DEVELOPMENT; TUMOR-SUPPRESSOR; NF2; MUTATION; PATIENT; MERLIN; MOUSE; MRI; NF2/MERLIN AB Purpose: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder associated primarily with bilateral schwannomas seen on the superior vestibular branches of the eighth cranial nerves. Significant morbidity can result from surgical treatment of these tumors. Meningiomas, ependymomas, and other benign central nervous system tumors are also common in NF2. The lack of effective treatments for NF2 marks an unmet medical need. Experimental Design: Here, we provide recommendations from a workshop, cochaired by Drs. D. Gareth Evans and Marco Giovannini, of 36 international researchers, physicians, representatives of the biotechnology industry, and patient advocates on how to accelerate progress toward NF2 clinical trials. Results: Workshop participants reached a consensus that, based on current knowledge, the time is right to plan and implement NF2 clinical trials. Obstacles impeding NF2 clinical trials and how to address them were discussed, as well as the candidate therapeutic pipeline for NF2. Conclusions: Both phase 0 and phase 11 NF2 trials are near-term options for NF2 clinical trials. The number of NF2 patients in the population remains limited, and successful recruitment will require ongoing collaboration efforts between NF2 clinics. (Clin Cancer Res 2009;15(16):5032-9) C1 [Giovannini, Marco] House Ear Res Inst, Ctr Neural Tumor Res, Los Angeles, CA 90057 USA. [Evans, D. Gareth] St Marys Hosp, Manchester M13 0JH, Lancs, England. [Kalamarides, Michel] Hop Beaujon, APHP, Clichy, France. [Allen, Jeffrey; Golfinos, John; Karajannis, Matthias; Roehm, Pamela] NYU, New York, NY 10003 USA. [Law, Meng] Mt Sinai Sch Med, New York, NY USA. [Yohay, Kaleb] Cornell Univ, Med Ctr, New York, NY 10021 USA. [Blakeley, Jaishri; Belzberg, Allan] Johns Hopkins Univ, Baltimore, MD USA. [Babovic-Vuskanovic, Dusica] Mayo Clin, Rochester, MN USA. [Bollag, Gideon] Plexxikon Inc, Berkeley, CA USA. [DiTomaso, Emmanuelle; Harris, Gordon; McClatchey, Andrea] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Jacob, Abraham; Welling, D. Bradley] Ohio State Univ, Columbus, OH 43210 USA. [Kalpana, Ganjam] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Korf, Bruce] Univ Alabama, Birmingham, AL USA. [Kurzrock, Razelle] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Tonsgard, James H.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Widemann, Brigitte] NCI, Bethesda, MD 20892 USA. RP Giovannini, M (reprint author), House Ear Res Inst, Ctr Neural Tumor Res, 2100 W 3rd St, Los Angeles, CA 90057 USA. EM mgiovannini@hei.org OI Yohay, Kaleb/0000-0001-5560-3392; Karajannis, Matthias/0000-0002-7151-6528; Evans, Gareth/0000-0002-8482-5784 FU Children's Tumor Foundation FX The NF2 Clinical Trials Consensus Workshop was convened and funded by the Children's Tumor Foundation. NR 36 TC 39 Z9 42 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2009 VL 15 IS 16 BP 5032 EP 5039 DI 10.1158/1078-0432.CCR-08-3011 PG 8 WC Oncology SC Oncology GA 484DX UT WOS:000269024900004 PM 19671848 ER PT J AU Rodig, SJ Mino-Kenudson, M Dacic, S Yeap, BY Shaw, A Barletta, JA Stubbs, H Law, K Lindeman, N Mark, E Janne, PA Lynch, T Johnson, BE Iafrate, AJ Chirieac, LR AF Rodig, Scott J. Mino-Kenudson, Mari Dacic, Sanja Yeap, Beow Y. Shaw, Alice Barletta, Justine A. Stubbs, Hannah Law, Kenny Lindeman, Neal Mark, Eugene Janne, Pasi A. Lynch, Thomas Johnson, Bruce E. Iafrate, A. John Chirieac, Lucian R. TI Unique Clinicopathologic Features Characterize ALK-Rearranged Lung Adenocarcinoma in the Western Population SO CLINICAL CANCER RESEARCH LA English DT Article ID EML4-ALK FUSION GENE; RING CELL-CARCINOMA; BRONCHIOLOALVEOLAR PATHOLOGICAL SUBTYPE; INFLAMMATORY MYOFIBROBLASTIC TUMORS; EGFR MUTATIONS; ACTIVATING MUTATIONS; HISTOLOGIC SUBTYPE; PROSTATE-CANCER; KINASE GENE; LYMPHOMA AB Purpose: The anaplastic large cell kinase gene (ALK) is rearranged in similar to 5% of lung adenocarcinomas within the Asian population. We evaluated the incidence and the characteristics of ALK-rearranged lung adenocarcinomas within the western population and the optimal diagnostic modality to detect ALK rearrangements in routine clinical practice. Experimental Design: We tested 358 lung adenocarcinomas from three institutions for ALK rearrangements by fluorescent in situ hybridization (FISH) and immunohistochemistry with and without tyramide amplification. The clinicopathologic characteristics of tumors with and without ALK rearrangements were compared. Results: We identified 20 (5.6%) lung adenocarcinomas with ALK rearrangements within our cohort of western patients. ALK rearrangement was associated with younger age (P = 0.0002), never smoking (P < 0.0001), advanced clinical stage (P = 0.0001), and a solid histology with signet-ring cells (P < 0.0001). ALK rearrangement was identified by FISH in 95% of cases and immunohistochemistry with and without tyramide amplification in 80% and 40% of cases, respectively, but neither FISH nor immunohistochemistry alone detected all cases with ALK rearrangement on initial screening. None of the ALK-rearranged tumors harbored coexisting EGFR mutations. Conclusions: Lung adenocarcinomas with ALK rearrangements are uncommon in the western population and represent a distinct entity of carcinomas with unique characteristics. For suspected cases, dual diagnostic testing, with FISH and immunohistochemistry, should be considered to accurately identify lung adenocarcinomas with ALK rearrangement. (Clin Cancer Res 2009;15(16):5216-23) C1 [Mino-Kenudson, Mari; Stubbs, Hannah; Mark, Eugene; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Rodig, Scott J.; Barletta, Justine A.; Law, Kenny; Lindeman, Neal; Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Yeap, Beow Y.; Shaw, Alice; Lynch, Thomas] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02115 USA. [Janne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dacic, Sanja] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 15 Fruit St, Boston, MA 02115 USA. EM aiafrate@partners.org; lchirieac@partners.org FU Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence in Lung Cancer [2P50 CA090578-06, R01-135257, R01-136851] FX Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence in Lung Cancer grant 2P50 CA090578-06. Supported in part by R01-135257 and R01-136851 (P.A. Janne) NR 48 TC 340 Z9 369 U1 1 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 AUG 15 PY 2009 VL 15 IS 16 BP 5216 EP 5223 DI 10.1158/1078-0432.CCR-09-0802 PG 8 WC Oncology SC Oncology GA 484DX UT WOS:000269024900025 PM 19671850 ER PT J AU Jackman, DM Miller, VA Cioffredi, LA Yeap, BY Janne, PA Riely, GJ Ruiz, MG Giaccone, G Sequist, LV Johnson, BE AF Jackman, David M. Miller, Vincent A. Cioffredi, Leigh-Anne Yeap, Beow Y. Jaenne, Pasi A. Riely, Gregory J. Ruiz, Marielle Gallegos Giaccone, Giuseppe Sequist, Lecia V. Johnson, Bruce E. TI Impact of Epidermal Growth Factor Receptor and KRAS Mutations on Clinical Outcomes in Previously Untreated Non-Small Cell Lung Cancer Patients: Results of an Online Tumor Registry of Clinical Trials SO CLINICAL CANCER RESEARCH LA English DT Article ID CHEMOTHERAPY-NAIVE PATIENTS; PREVIOUSLY TREATED PATIENTS; SOUTHWEST-ONCOLOGY-GROUP; PHASE-II; BRONCHIOLOALVEOLAR-CARCINOMA; ACTIVATING MUTATIONS; GEFITINIB THERAPY; TYROSINE KINASE; EGFR MUTATIONS; GENE-MUTATIONS AB Purpose: The impact of epidermal growth factor receptor (EGFR) and KRAS genotypes on outcomes with erlotinib or gefitinib therapy continues to be debated. This study combines patient data from five trials in predominantly Western populations to assess the impact of EGFR and KRAS mutations on first-line therapy with an EGFR-tyrosine kinase inhibitor (TKI) and compare clinical versus molecular predictors of sensitivity. Experimental Design: Chemotherapy-naive patients with advanced non-small cell lung cancer and known EGFR mutation status treated with erlotinib or gefitinib monotherapy as part of a clinical trial were eligible for inclusion. Patients received daily erlotinib (150 mg) or gefitinib (250 mg) until disease progression or unacceptable toxicity. Data were collected in a password-protected web database. Clinical outcomes were analyzed to look for differences based on EGFR and KRAS genotypes, as well as clinical characteristics. Results: Patients (223) from five clinical trials were included. Sensitizing EGFR mutations were associated with a 67% response rate, time to progression (TTP) of 11.8 months, and overall survival of 23.9 months. Exon 19 deletions were associated with longer median TTP and overall survival compared with L858R mutations. Wild-type EGFR was associated with poorer outcomes (response rate, 3%; TTP, 3.2 months) irrespective of KRAS status. No difference in outcome was seen between patients harboring KRAS transition versus transversion mutations. EGFR genotype was more effective than clinical characteristics at selecting appropriate patients for consideration of first-line therapy with an EGFR-TKI. Conclusion: EGFR mutation status is associated with sensitivity to treatment with an EGFR-TKI in patients with advanced non-small cell lung cancer. Patients harboring sensitizing EGFR mutations should be considered for first-line erlotinib or gefitinib. (Clin Cancer Res 2009;15(16):5267-73) C1 [Jackman, David M.; Cioffredi, Leigh-Anne; Jaenne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Jackman, David M.; Yeap, Beow Y.; Jaenne, Pasi A.; Sequist, Lecia V.; Johnson, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Miller, Vincent A.; Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, New York, NY 10021 USA. [Ruiz, Marielle Gallegos] Vrije Univ Amsterdam, Amsterdam, Netherlands. [Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Jackman, DM (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 44 Binney St, Boston, MA 02115 USA. EM djackman@partners.org RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 FU The American Society of Clinical Oncology (ASCO) Cancer Foundation Translational Research Professorship; NIH [5RO1 CA 114465-05]; International Association for the Study of Lung Cancer Fellowship; Alice and Stephen D. Cutler Investigator Fund FX The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 27 TC 233 Z9 249 U1 1 U2 9 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 AUG 15 PY 2009 VL 15 IS 16 BP 5267 EP 5273 DI 10.1158/1078-0432.CCR-09-0888 PG 7 WC Oncology SC Oncology GA 484DX UT WOS:000269024900031 PM 19671843 ER PT J AU Restrepo, MI AF Restrepo, Marcos I. TI Efficacy of Intravenous Infusion of Doripenem SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INADEQUATE ANTIMICROBIAL TREATMENT; VENTILATOR-ASSOCIATED PNEUMONIA; NOSOCOMIAL PNEUMONIA; MULTICENTER; INFECTIONS; SAFETY AB Initial treatment of nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP), is usually empirical. The use of a broad-spectrum antibiotic regimen to treat NP-VAP that is active against suspected multidrug-resistant pathogens maximizes the likelihood of a favorable outcome. In a post hoc analysis of pooled data from 2 prospective, randomized, open-label, phase 3 NP-VAP trials, doripenem, a new broad-spectrum carbapenem with antipseudomonal activity, demonstrated noninferiority to standard comparator regimens (imipenem and piperacillin-tazobactam) with regard to clinical and microbiological outcomes. In subgroup analyses, doripenem continued to show noninferiority to the comparator drugs in achieving clinical and microbiological cures in populations at high risk of multidrug-resistant infection, such as patients with late-onset VAP (defined as patients who develop VAP > 5 days after intubation) or those with NP-VAP caused by Pseudomonas aeruginosa or complicated by bacteremia. Overall, the clinical data indicate that doripenem has the potential to be an important option in the treatment of NP, including VAP. C1 [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] VERDICT S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Restrepo, MI (reprint author), VERDICT Ctr 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU Ortho-McNeil-Janssen Scientific Affairs FX Financial support. Ortho-McNeil-Janssen Scientific Affairs.; Supplement sponsorship. This article was published as part of a supplement entitled "Doripenem: A New Carbapenem in the Treatment of Nosocomial Infection," sponsored by Ortho-McNeil-Janssen Scientific Affairs. NR 21 TC 2 Z9 2 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 15 PY 2009 VL 49 SU 1 BP S17 EP S27 DI 10.1086/599812 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 472MJ UT WOS:000268135600004 PM 19619018 ER PT J AU Yagiz, K Rittling, SR AF Yagiz, Kader Rittling, Susan R. TI Both cell-surface and secreted CSF-1 expressed by tumor cells metastatic to bone can contribute to osteoclast activation SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Osteoclast; Bone metastasis; M-CSF; Syngeneic ID COLONY-STIMULATING FACTOR; OSTEOPONTIN-DEFICIENT MICE; BREAST-CANCER METASTASIS; HORMONE-RELATED PROTEIN; TGF-BETA; FACTOR-I; MATURE OSTEOCLASTS; MOUSE OSTEOPONTIN; MACROPHAGE; FORM AB Tumors metastatic to the bone produce factors that cause massive bone resorption mediated by osteoclasts in the bone microenvironment. Colony stimulating factor (CSF-1) is strictly required for the formation and survival of active osteoclasts, and is frequently produced by tumor cells. Here we hypothesize that the CSF-1 made by tumor cells contributes to bone destruction in osteolytic bone metastases. We show that high level CSF-1 protected osteoclasts from suppressive effects of transforming growth factor beta (TGF-beta). r3T cells, a mouse mammary tumor cell line that forms osteolytic bone metastases, express abundant CSF-1 in vitro as both a secreted and a membrane-spanning cell-surface glycoprotein, and we show that both the secreted and the cell-surface form of CSF-1 made by r3T cells can support osteoclast formation in co-culture experiments in the presence of RankL. Mice with r3T bone metastases have elevated levels of both circulating and bone-associated CSF-1, and the majority of CSF-1 found in bone metastases is associated with the tumor cells. These results support the idea that tumor-cell produced CSF-1 contributes to osteoclast development and survival in bone metastasis. (C) 2009 Elsevier Inc. All rights reserved. C1 [Yagiz, Kader; Rittling, Susan R.] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Rittling, Susan R.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02138 USA. RP Rittling, SR (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM srittling@forsyth.org FU NIH [DK067685] FX The authors appreciate expert technical help provided by Craig Zetterberg, the kind gift of MC3T3 cells from Dr. Toshi Kawai, and the gift of MLOY4 cells from Lynda Bonewald. Special thanks to Meena Chellaiah for advice on osteoclast culture and the kind gift of GST-RANKL plasmid. Supported by NIH #DK067685. NR 57 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 15 PY 2009 VL 315 IS 14 BP 2442 EP 2452 DI 10.1016/j.yexcr.2009.05.002 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 468JG UT WOS:000267813000010 PM 19427849 ER PT J AU Lee, JT AF Lee, Jeannie T. TI Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome SO GENES & DEVELOPMENT LA English DT Review DE X-chromosome inactivation; chromatin modifier; dosage compensation; epigenetic regulation; noncoding RNA ID EARLY MOUSE EMBRYOS; HISTONE METHYLTRANSFERASE ACTIVITY; H3 LYSINE-27 METHYLATION; XIST GENE; DOSAGE COMPENSATION; ANTISENSE TRANSCRIPTION; TSIX TRANSCRIPTION; NONCODING RNAS; HUMAN-CELLS; CHROMATIN-STRUCTURE AB Transcriptome studies are revealing that the eukaryotic genome actively transcribes a diverse repertoire of large noncoding RNAs (ncRNAs), many of which are un-annotated and distinct from the small RNAs that have garnered much attention in recent years. Why are they so pervasive, and do they have a function? X-chromosome inactivation (XCI) is a classic epigenetic phenomenon associated with many large ncRNAs. Here, I provide a perspective on how XCI is achieved in mice and suggest how this knowledge can be applied to the rest of the genome. Emerging data indicate that long ncRNAs can function as guides and tethers, and may be the molecules of choice for epigenetic regulation: First, unlike proteins and small RNAs, large ncRNAs remain tethered to the site of transcription, and can therefore uniquely direct allelic regulation. Second, ncRNAs command a much larger sequence space than proteins, and can therefore achieve very precise spatiotemporal control of development. These properties imply that long noncoding transcripts may ultimately rival small RNAs and proteins in their versatility as epigenetic regulators, particularly for locus- and allele-specific control. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol,Howard Hughes Med Inst, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol,Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute NR 119 TC 172 Z9 180 U1 1 U2 22 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 15 PY 2009 VL 23 IS 16 BP 1831 EP 1842 DI 10.1101/gad.1811209 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 483JT UT WOS:000268961100001 PM 19684108 ER PT J AU van der Meer, P Groenveld, HF Januzzi, JL van Veldhuisen, DJ AF van der Meer, P. Groenveld, H. F. Januzzi, J. L., Jr. van Veldhuisen, D. J. TI Erythropoietin treatment in patients with chronic heart failure: a meta-analysis SO HEART LA English DT Article ID CHRONIC KIDNEY-DISEASE; DARBEPOETIN-ALPHA; ANEMIC PATIENTS; DOUBLE-BLIND; MORTALITY; TRIAL; QUALITY AB Background: Anaemia is common in patients with chronic heart failure (HF), and erythropoiesis stimulating proteins (ESPs) are frequently used for its treatment. However, recent studies in patients with malignancies and renal failure have raised concerns about the safety of these agents. Objective: To determine whether treatment of anaemic patients with chronic HF with ESPs is associated with an effect on morbidity and mortality. Data sources: A systematic literature search in Medline, the Cochrane Controlled Trials Register Database and ClinicalTrials.gov through July 2008 was performed. Study selection: Randomised clinical trials comparing the effect of ESP treatment with placebo or usual care in anaemic patients with HF were included. Results: Seven randomised controlled trials were identified that enrolled 650 patients, of whom 363 were treated with ESPs and 287 with placebo. ESP treatment had a significantly lower risk of HF hospitalisation (risk ratio (RR)= 0.59; 95% CI 0.41 to 0.86; p = 0.006). There was no significant difference in the mortality risk between the two groups (RR = 0.69; 95% CI 0.39 to 1.23; p = 0.21). No significant differences were observed in the occurrence of hypertension or venous thrombosis. Conclusions: In chronic HF, treatment with ESPs is not associated with a higher mortality rate or more adverse events, whereas a beneficial effect on HF hospitalisation is seen. These outcomes are in contrast with studies in cancer and kidney disease, and support a large phase III morbidity and mortality trial of anaemia correction in patients with chronic HF. C1 [van der Meer, P.; Groenveld, H. F.; van Veldhuisen, D. J.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands. [van der Meer, P.; Januzzi, J. L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA USA. RP van der Meer, P (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Hanzepl 1, NL-9700 RB Groningen, Netherlands. EM p.van.der.meer@thorax.umcg.nl RI van Veldhuisen, Dirk Jan/E-8967-2014 FU Netherlands Heart Foundation [D97-017]; The Netherlands Organization for Scientific Research [825-07-011] FX This work was supported by the Netherlands Heart Foundation (D97-017 to DJvV) and The Netherlands Organization for Scientific Research (Rubicon grant: 825-07-011 to PvdM). The funding source did not have any influence on the conduction and interpretation of the study. NR 28 TC 76 Z9 77 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD AUG 15 PY 2009 VL 95 IS 16 BP 1309 EP 1314 DI 10.1136/hrt.2008.161091 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 475WZ UT WOS:000268397600005 PM 19168472 ER PT J AU Swami, M Hendricks, AE Gillis, T Massood, T Mysore, J Myers, RH Wheeler, VC AF Swami, Meera Hendricks, Audrey E. Gillis, Tammy Massood, Tiffany Mysore, Jayalakshmi Myers, Richard H. Wheeler, Vanessa C. TI Somatic expansion of the Huntington's disease CAG repeat in the brain is associated with an earlier age of disease onset SO HUMAN MOLECULAR GENETICS LA English DT Article ID POLYMERASE-CHAIN-REACTION; KNOCK-IN MOUSE; TRINUCLEOTIDE REPEAT; OF-ONSET; VENEZUELAN KINDREDS; DNA INSTABILITY; HD MAPS; GENE; LENGTH; MODIFIER AB The age of onset of Huntington's disease (HD) is determined primarily by the length of the HD CAG repeat mutation, but is also influenced by other modifying factors. Delineating these modifiers is a critical step towards developing validated therapeutic targets in HD patients. The HD CAG repeat is somatically unstable, undergoing progressive length increases over time, particularly in brain regions that are the targets of neurodegeneration. Here, we have explored the hypothesis that somatic instability of the HD CAG repeat is itself a modifier of disease. Using small-pool PCR, we quantified somatic instability in the cortex region of the brain from a cohort of HD individuals exhibiting phenotypic extremes of young and old disease onset as predicted by the length of their constitutive HD CAG repeat lengths. After accounting for constitutive repeat length, somatic instability was found to be a significant predictor of onset age, with larger repeat length gains associated with earlier disease onset. These data are consistent with the hypothesis that somatic HD CAG repeat length expansions in target tissues contribute to the HD pathogenic process, and support pursuing factors that modify somatic instability as viable therapeutic targets. C1 [Swami, Meera; Gillis, Tammy; Mysore, Jayalakshmi; Wheeler, Vanessa C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Hendricks, Audrey E.] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA. [Massood, Tiffany; Myers, Richard H.] Boston Univ, Dept Neurol, Sch Publ Hlth, Boston, MA 02118 USA. RP Wheeler, VC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM wheeler@helix.mgh.harvard.edu RI Hendricks, Audrey/I-4127-2016; OI Hendricks, Audrey/0000-0002-7152-0287; Myers, Richard/0000-0002-8365-2674 FU National Institutes of Health [NS049206, P50NS16367-28]; Jerry MacDonald HD Research Fund FX This work was supported by the National Institutes of Health [NS049206 to V. C. W, P50NS16367-28 'Huntington Disease Center Without Walls' to R. H. M], and the Jerry MacDonald HD Research Fund. NR 47 TC 67 Z9 68 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 15 PY 2009 VL 18 IS 16 BP 3039 EP 3047 DI 10.1093/hmg/ddp242 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 475BN UT WOS:000268330900010 PM 19465745 ER PT J AU Linas, BP Losina, E Rockwell, A Walensky, RP Cranston, K Freedberg, KA AF Linas, Benjamin P. Losina, Elena Rockwell, Annette Walensky, Rochelle P. Cranston, Kevin Freedberg, Kenneth A. TI Improving Outcomes in State AIDS Drug Assistance Programs SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy/46th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 25, 2008 CL Washington, DC SP Infect Dis Soc Amer DE ADAP; AIDS; anti-HIV agents*/therapeutic use; CD4 lymphocyte count; government programs; resource allocation ID ACTIVE ANTIRETROVIRAL THERAPY; MULTIPLE VIROLOGICAL FAILURES; MYCOBACTERIUM-AVIUM COMPLEX; UNITED-STATES; HIV-INFECTION; COST-EFFECTIVENESS; CONTROLLED-TRIAL; NAIVE PATIENTS; EFFICACY; LOPINAVIR/RITONAVIR AB Background: State AIDS Drug Assistance Programs (ADAPs) provide antiretroviral medications to patients with no acccss to medications. Resource constraints limit the ability of many ADAPs to meet demand for services. Objective: To determine ADAP eligibility criteria that minimize morbidity and mortality and contain costs. Methods: We used Discrete Event Simulation to model the progression of HIV-infected patients and track the utilization of all ADAP. Outcomes included 5-year mortality and incidence of first opportunistic infection or death and time to starting antiretroviral therapy (ART). We compared expected outcomes for 2 policies: (1) first-come first-served (FCFS) eligibility for all with CD4 Count <= 350/mu L (current standard) and (2) CD4 Count prioritized eligibility for those with CD4 counts below a defined threshold. Results: In the base case, prioritizing patients with CD4 counts <= 250/mu L led to lower 5-year mortality than FCFS eligibility (2.77 vs. 3.27 deaths per 1000 person-months) and to a lower incidence of first Opportunistic infection or death (5.55 vs. 6.98 events per 1000 person-months). CD4-based eligibility reduced the time to starting ART for patients with CD4 Counts :<= 200/mu L. In sensitivity analyses, CD4-based eligibility consistently led to lower morbidity and mortality than FCFS eligibility. Conclusion: When resources are limited, programs that provide ART call improve Outcomes by prioritizing patients with low CD4 Counts. C1 [Linas, Benjamin P.; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02115 USA. [Linas, Benjamin P.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Harvard Ctr AIDS Res CFAR, Boston, MA USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Rockwell, Annette; Cranston, Kevin] Massachusetts Dept Publ Hlth HIV AIDS Bur, Boston, MA USA. RP Linas, BP (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02115 USA. EM blinas@partners.org FU NIAID NIH HHS [P30AI060354, K24AI062476, K24 AI062476, K01 AI073193-02, R37 AI042006, R37 AI042006-13, R37AI42006, K24 AI062476-01, K01 AI073193, K01AI073193, P30 AI060354]; NIMH NIH HHS [R01 MH073445, R01MH073445] NR 42 TC 8 Z9 8 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 15 PY 2009 VL 51 IS 5 BP 513 EP 521 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 475GM UT WOS:000268346600002 PM 19561518 ER PT J AU Anis, AH Nosyk, B Sun, HY Guh, DP Bansback, N Li, X Barnett, PG Joyce, V Swanson, KM Kyriakides, TC Holodniy, M Cameron, DW Brown, ST AF Anis, Aslam H. Nosyk, Bohdan Sun, Huiying Guh, Daphne P. Bansback, Nick Li, Xin Barnett, Paul G. Joyce, Vilija Swanson, Kathleen M. Kyriakides, Tassos C. Holodniy, Mark Cameron, D. William Brown, Sheldon T. CA OPTIMA Team TI Quality of Life of Patients With Advanced HIV/AIDS: Measuring the Impact of Both AIDS-Defining Events and Non-AIDS Serious Adverse Events SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy/46th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 25, 2008 CL Washington, DC SP Infect Dis Soc Amer DE AIDS-defining events; HIV/AIDS; HRQoL; non-AIDS serious adverse events ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH UTILITIES INDEX; HIV-INFECTED PATIENTS; MEDICAL OUTCOMES; CLINICAL-TRIAL; HAART ERA; VALIDITY; DISEASE; MULTIATTRIBUTE; INSTRUMENTS AB Objective: To investigate the relative magnitude and duration of impact of AIDS-defining events (ADEs) and non-AIDS serious adverse events (SAEs) on health-related quality of life (HRQoL) among patients with advanced HIV/AIDS. Methods: We use data from OPTIMA (OPTions In Management with Antiretrovirals), a multinational, randomized, open, control, clinical management trial of treatment strategies for patients with multidrug-resistant HIV and advanced immune disease. Longitudinal models were used to determine the effects of ADEs and SAEs oil HRQoL across periods before, during, and after event onset. The Medical Outcomes Study HIV Health Survey (MOS-HIV) physical and mental health summary scores (MOS-PHS and MOS-MHS), EQ-5D, and the Health Utilities Index Mark 3 HRQoL measures were all assessed at regular follow-up intervals during the trial. Results: ADEs occurred much less frequently than SAEs (n = 147 vs. n = 821) in the study sample population of 368 patients, during median follow-up of 3.96 years. Although both ADEs and SAEs had significant negative impacts on HRQoL, SAEs had at least as large an impact upon HRQoL as ADEs when both were included in a multivariate linear regression model, controlling for other covariates. However, the effect of ADEs on HRQoL was more persistent, with larger magnitude of effect across all instruments in time intervals further from the onset of the event. Conclusions: Non-AIDS SAEs occurring in patients with late-stage HIV/AIDS seem to have at least as important an immediate impact on patient HRQoL as ADEs; however, the impact of ADEs seems to be more persistent. Our findings call for a greater emphasis oil the detection and active prevention of non-AIDS SAEs in patients with late-stage HIV/AIDS. C1 [Anis, Aslam H.; Nosyk, Bohdan; Sun, Huiying; Guh, Daphne P.; Bansback, Nick; Li, Xin] Canadian HIV Trials Network, Vancouver, BC, Canada. [Anis, Aslam H.] Univ British Columbia, Fac Med, Sch Populat & Publ Hlth, Vancouver, BC, Canada. [Barnett, Paul G.; Joyce, Vilija] Off Res & Dev, US Dept Vet Affairs, Cooperat Studies Program, VA Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Swanson, Kathleen M.] Clin Res Pharm Coordinating Ctr, Cooperat Studies Program, Regulatory Affairs & Clin Compliance Sect, Albuquerque, NM USA. [Kyriakides, Tassos C.] VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Holodniy, Mark] VA Med Ctr, Palo Alto, CA USA. [Cameron, D. William] Univ Ottawa, Ottawa Hosp, Div Infect Dis, Ottawa, ON, Canada. [Brown, Sheldon T.] Mt Sinai Sch Med, James J Peters VA Med Ctr, Dept Med, Infect Dis Sect, New York, NY USA. RP Anis, AH (reprint author), St Pauls Hosp, Canadian HIV Trials Network, 620-1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada. EM aslam.anis@ubc.ca RI Joyce, Vilija/A-2578-2013; OI Joyce, Vilija/0000-0002-2484-4625; Cameron, Bill/0000-0002-0090-3539 FU Medical Research Council NR 42 TC 27 Z9 27 U1 4 U2 7 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 AUG 15 PY 2009 VL 51 IS 5 BP 631 EP 639 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 475GM UT WOS:000268346600018 PM 19430303 ER PT J AU Beltman, JB Henrickson, SE von Andrian, UH de Boer, RJ Maree, AFM AF Beltman, Joost B. Henrickson, Sarah E. von Andrian, Ulrich H. de Boer, Rob J. Maree, Athanasius F. M. TI Towards estimating the true duration of dendritic cell interactions with T cells SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Cellular Potts Model; Censored data; Immunological synapse; T cell-DC interactions; T cell motility; Multi-photon microscopy ID LYMPH-NODES; IN-VIVO; REAL-TIME; 2-PHOTON MICROSCOPY; B-CELLS; ACTIVATION; BEHAVIOR; TOLERANCE; MIGRATION; IMMUNITY AB To initiate an adaptive immune response, T cells need to interact with dendritic cells (DCs), and the duration of these interactions plays an important role. In vitro and in vivo experiments have generally tried to estimate the required period of opportunity for T cell stimulation rather than the duration of individual T cell-DC interactions. Since the application of multi-photon microscopy (MPM) to living lymphoid tissues, the interactions between immune cells, as well as the duration thereof, can directly be observed in vivo. Indeed, long-lasting interactions between T cells and DCs were shown to be important for the onset of immune responses. However, because MPM imaging is typically restricted to experiments lasting 1 h, and because T cell-DC conjugates frequently move into and out of the imaged volume, it is difficult to estimate the true duration of interactions from MPM contact data. Here, we present a method to properly make such an estimate of (the average of) the distribution of contact durations. We validate the method by applying it to spatially explicit computer simulations where the true distribution of contact duration is known. Finally, we apply our analysis to a large experimental data set of T-DC contacts, and predict an average contact time of about three hours. However, we identify a mismatch between the experimental data and the model predictions, and investigate possible causes of the mismatch, including minor tissue drift during imaging experiments. We discuss in detail how future experiments can be optimized such that MPM contact data will be minimally affected by these factors. (C) 2009 Elsevier B.V. All rights reserved. C1 [Beltman, Joost B.; de Boer, Rob J.; Maree, Athanasius F. M.] Univ Utrecht, NL-3584 CH Utrecht, Netherlands. [Henrickson, Sarah E.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Henrickson, Sarah E.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Beltman, JB (reprint author), Univ Utrecht, Padualaan 8, NL-3584 CH Utrecht, Netherlands. EM J.B.Beltman@uu.nl RI De Boer, Rob/B-6050-2011; von Andrian, Ulrich/A-5775-2008; OI De Boer, Rob/0000-0002-2130-691X; Maree, Athanasius F. M./0000-0003-2689-2484 FU Netherlands Organisation for Scientific Research (NWO) [916.86.080, 016.048.603]; National Institutes of Health (NIH) [AI069259, AI072252, HL07623]; Medical Scientist Training Program; Osaka University Immunology Frontier Research Center FX We thank Veronica Grieneisen, Marianne Jonker, Vitaly Ganusov and anonymous referees for commenting extensively on a previous version of the paper and/or statistical advice. This work was supported by the Netherlands Organisation for Scientific Research (NWO), grants 916.86.080 (JBB) and 016.048.603 (JBB, RJDB), by the National Institutes of Health (NIH), grants AI069259 (UHvA), AI072252 (UHvA), HL07623 (SEH) and a Medical Scientist Training Program (SEH), and by the Osaka University Immunology Frontier Research Center (SEH). The authors have no conflicting financial interests. NR 44 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD AUG 15 PY 2009 VL 347 IS 1-2 BP 54 EP 69 DI 10.1016/j.jim.2009.05.013 PG 16 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 485XM UT WOS:000269158800009 PM 19520083 ER PT J AU Ahmed, F Friend, S George, TC Barteneva, N Lieberman, J AF Ahmed, Fariyal Friend, Sherree George, Thaddeus C. Barteneva, Natasha Lieberman, Judy TI Numbers matter: Quantitative and dynamic analysis of the formation of an immunological synapse using imaging flow cytometry SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Imaging flow cytometry; Immunological synapse; Flow cytometry; Fluorescence microscopy ID CYTOTOXIC T-LYMPHOCYTES; SUPRAMOLECULAR ACTIVATION CLUSTERS; KAPPA-B ACTIVATION; CELL-ACTIVATION; CYTOLYTIC ACTIVITY; IMMUNE SYNAPSE; RING JUNCTION; RECEPTOR; ANTIGEN; CTL AB Activation of T lymphocytes by antigen-presenting cells (APC) results in the formation of an immunological synapse. Following contact with the target cell, key signaling and adhesion molecules polarize within minutes to hours to the T cell-APC interface. Multispectral imaging flow cytometry, a new technology which combines flow cytometry with imaging, was used to visualize and quantify the recruitment of the CD3 epsilon and Lck signaling molecules during the evolution of an immune synapse. Using this technology, thousands of T cell/macrophage conjugates could be analyzed for each experimental time point. Following Ca(++) triggered T cell activation, the dynamics of Lck and CD3 epsilon recruitment to the synapse, analyzed by two independent methods, were comparable. However, CD3 epsilon exhibited longer residence times (>8 min) at the synapse than Lck. (C) 2009 Elsevier B.V. All rights reserved. C1 [Ahmed, Fariyal; Barteneva, Natasha; Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Friend, Sherree; George, Thaddeus C.] Amnis Corp, Seattle, WA 98121 USA. RP Barteneva, N (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM barteneva@idi.harvard.edu; lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIH [S10 RR023459]; Harvard Center for AIDS Research; Canadian Institutes for Health Research FX This work was supported by NIH S10 RR023459 (JL, NB), the Harvard Center for AIDS Research (JL, FA) and the Canadian Institutes for Health Research (FA). NR 37 TC 13 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD AUG 15 PY 2009 VL 347 IS 1-2 BP 79 EP 86 DI 10.1016/j.jim.2009.05.014 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 485XM UT WOS:000269158800011 PM 19524586 ER PT J AU Iweala, OI Smith, DW Matharu, KS Sada-Ovalle, I Nguyen, DD DeKruyff, RH Umetsu, DT Behar, SM Nagler, CR AF Iweala, Onyinye I. Smith, Donald W. Matharu, Kabir S. Sada-Ovalle, Isabel Nguyen, Deanna D. DeKruyff, Rosemarie H. Umetsu, Dale T. Behar, Samuel M. Nagler, Cathryn R. TI Vaccine-Induced Antibody Isotypes Are Skewed by Impaired CD4 T Cell and Invariant NKT Cell Effector Responses in MyD88-Deficient Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; SALMONELLA-TYPHIMURIUM; IMMUNE-RESPONSES; DENDRITIC CELLS; INNATE IMMUNITY; IN-VIVO; MICROBIAL INFECTIONS; CYTOKINE PRODUCTION; LYMPHOCYTE EGRESS; ADAPTIVE IMMUNITY AB The requirement for TLR signaling in the initiation of an Ag-specific Ab response is controversial. In this report we show that a novel OVA-expressing recombinant Salmonella vaccine (Salmonella-OVA) elicits a Th1-biased cell-mediated and serum Ab response upon oral or i.p. immunization of C57BL/6 mice. In MyD88(-/-) mice, Th1-dependent Ab responses are greatly reduced while Th2-dependent Ab isotypes are elevated in response to oral and i.p., but not s.c. footpad, immunization. When the T effector response to oral vaccination is examined we find that activated, adoptively transferred Ag-specific CD4(+) T cells accumulate in the draining lymph nodes, but fail to produce IFN-gamma, in MyD88(-/-) mice. Moreover, CD1d tetramer staining shows that invariant NKT cells are activated in response to oral Salmonella-OVA vaccination in wild-type, but not MyD88(-/-), mice. Treatment with neutralizing Ab to CD1d reduces the OVA-specific Ab response only in MyD88-sufficient wild-type mice, suggesting that both Ag-specific CD4 T cell and invariant NKT cell effector responses to Salmonella-OVA vaccination are MyD88 dependent. Taken together, our data indicate that the type of adaptive immune response generated to this live attenuated vaccine is regulated by both the presence of MyD88-mediated signals and vaccination route, which may have important implications for future vaccine design. The Journal of Immunology, 2009, 183: 2252-2260. C1 [Iweala, Onyinye I.; Smith, Donald W.; Matharu, Kabir S.; Nagler, Cathryn R.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Nguyen, Deanna D.] Massachusetts Gen Hosp, Gastrointestinal Unit, Charlestown, MA 02129 USA. [Sada-Ovalle, Isabel; Behar, Samuel M.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [DeKruyff, Rosemarie H.; Umetsu, Dale T.] Childrens Hosp, Boston, MA 02115 USA. [DeKruyff, Rosemarie H.; Umetsu, Dale T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Nagler, CR (reprint author), Univ Chicago, BSD Dept Pathol Committe Immunol, 5841 S Maryland Ave MC 3083, Chicago, IL 60637 USA. EM cnagler@bsd.uchicago.edu OI Behar, Samuel/0000-0002-3374-6699 FU National Institutes of Health [DK 55678]; Massachusetts General Hospital Center for the Study of Inflammatory Bowel Disease [DK 43551]; Predoctoral Training Fellowships [T32 A107529, F31 AI054229] FX This work was supported by National Institutes of Health Grant DK 55678, the Massachusetts General Hospital Center for the Study of Inflammatory Bowel Disease (Grant DK 43551), and Predoctoral Training Fellowships T32 A107529 (to D.W.S.) and F31 AI054229 (to O.I.I.). NR 68 TC 9 Z9 9 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2009 VL 183 IS 4 BP 2252 EP 2260 DI 10.4049/jimmunol.0804011 PG 9 WC Immunology SC Immunology GA 482RN UT WOS:000268906500009 PM 19620295 ER PT J AU Xing, CH Lee, SR Kim, WJ Wang, H Yang, YG Ning, MM Wang, XY Lo, EH AF Xing, Changhong Lee, Sunryung Kim, Woo Jean Wang, Hui Yang, Yong-Guang Ning, MingMing Wang, Xiaoying Lo, Eng H. TI Neurovascular Effects of CD47 Signaling: Promotion of Cell Death, Inflammation, and Suppression of Angiogenesis in Brain Endothelial Cells In Vitro SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE CD47; cell death; inflammation; angiogenesis; endothelial cell ID ACTIVATED PROTEIN-C; DENDRITIC CELLS; DEPENDENT INHIBITION; LEUKEMIC-CELLS; VLDL RECEPTOR; KINASE-A; THROMBOSPONDIN-1; STROKE; MECHANISMS; MIGRATION AB The concept of the neurovascular unit emphasizes that common signals and substrates underlie the physiology and pathophysiology of neuronal and endothelial compartments in brain. Recent data suggest that activation of the integrin-associated protein CD47 promotes neuronal cell death. Is it possible that CD47 may also negatively affect cerebral endothelial cells? Exposure of wild-type primary mouse cerebral endothelial cells to the CD47 ligand thrombospondin 1 (TSP-1) induced an increasing amount of cell death, whereas cytotoxicity was significantly decreased in cerebral endothelial cells derived from CD47 knockout mice. The specific CD47-activating peptide, 4N1K, similarly induced cell death in human brain microvascular endothelial cells. Promotion of inflammation was also involved because lower TSP-1 was able to up-regulate the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Finally, CD47 signaling may suppress angiogenesis because 4N1K significantly inhibited endothelial cell migration and tube formation in vitro. We conclude that CD47 signaling can negatively affect the viability and function of cerebral endothelial cells, further supporting the notion that CD47 may be a potential neurovascular target for stroke and brain injury. (C) 2009 Wiley-Liss, Inc. C1 [Xing, Changhong; Lee, Sunryung; Kim, Woo Jean; Ning, MingMing; Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol & Neurol, Boston, MA 02129 USA. [Lee, Sunryung] Cheju Natl Univ, Dept Biol, Cheju, South Korea. [Wang, Hui; Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Med, Boston, MA 02129 USA. RP Lo, EH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol & Neurol, Boston, MA 02129 USA. EM wangxi@helix.mgh.harvard.edu; Lo@helix.mgh.harvard.edu FU [R37-NS37074]; [R01-NS53560]; [R01-AI64569]; [K23-NS51588]; [R21-NS52498]; [P01-NS55104.] FX This study is supported in part by grants R37-NS37074, R01-NS53560, R01-AI64569, K23-NS51588, R21-NS52498, and P01-NS55104. NR 56 TC 19 Z9 19 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 15 PY 2009 VL 87 IS 11 BP 2571 EP 2577 DI 10.1002/jnr.22076 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 472GJ UT WOS:000268118100016 PM 19360900 ER PT J AU Meyer, JS Li, Y Chowdhury, MH Thornby, J AF Meyer, J. S. Li, Y. Chowdhury, M. H. Thornby, J. TI Combined mild diabetes with hypertension during aging increases white matter atrophy SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 5th International Congress on Vascular Dementia CY NOV 08-11, 2007 CL Budapest, HUNGARY C1 [Meyer, J. S.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Li, Y.; Chowdhury, M. H.; Thornby, J.] Baylor Coll Med, Michael E Debakey Vet Adm Med Ctr, Dept Neurol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD AUG 15 PY 2009 VL 283 IS 1-2 BP 258 EP 258 DI 10.1016/j.jns.2009.02.076 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 478SU UT WOS:000268609400120 ER PT J AU Siddappa, NB Song, RJ Kramer, VG Chenine, AL Velu, V Ong, H Rasmussen, RA Grisson, RD Wood, C Zhang, H Kankasa, C Amara, RR Else, JG Novembre, FJ Montefiori, DC Ruprecht, RM AF Siddappa, Nagadenahalli B. Song, Ruijiang Kramer, Victor G. Chenine, Agnes-Laurence Velu, Vijayakumar Ong, Helena Rasmussen, Robert A. Grisson, Ricky D. Wood, Charles Zhang, Hong Kankasa, Chipeppo Amara, Rama Rao Else, James G. Novembre, Francis J. Montefiori, David C. Ruprecht, Ruth M. TI Neutralization-Sensitive R5-Tropic Simian-Human Immunodeficiency Virus SHIV-2873Nip, Which Carries env Isolated from an Infant with a Recent HIV Clade C Infection (vol 83, pg 1422, 2009) SO JOURNAL OF VIROLOGY LA English DT Correction C1 [Siddappa, Nagadenahalli B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA. Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA. Univ Teaching Hosp, Lusaka, Zambia. Emory Univ, Yerkes Natl Primate Res Ctr, Dept Microbiol & Immunol, Div Microbiol & Immunol,Div Anim Resources, Atlanta, GA 30322 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Siddappa, NB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG 15 PY 2009 VL 83 IS 16 BP 8297 EP 8297 PG 1 WC Virology SC Virology GA 473LR UT WOS:000268208700051 ER PT J AU Kitamura, T Kitamura, YI Kobayashi, M Kikuchi, O Sasaki, T DePinho, RA Accili, D AF Kitamura, Tadahiro Kitamura, Yukari Ido Kobayashi, Masaki Kikuchi, Osamu Sasaki, Tsutomu DePinho, Ronald A. Accili, Domenico TI Regulation of Pancreatic Juxtaductal Endocrine Cell Formation by FoxO1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR FOXO1; FORKHEAD PROTEIN FOXO1; ADULT-MOUSE PANCREAS; BETA-CELLS; INSULIN ACTION; EXOCRINE PANCREAS; MICE; DIFFERENTIATION; PROGENITORS; RESISTANCE AB An understanding of the mechanisms that govern pancreatic endocrine cell ontogeny may offer strategies for their somatic replacement in diabetic patients. During embryogenesis, transcription factor FoxO1 is expressed in pancreatic progenitor cells. Subsequently, it becomes restricted to beta cells and to a rare population of insulin-negative juxtaductal cells (FoxO1(+) Ins(-)). It is unclear whether FoxO1(+) Ins(-) cells give rise to endocrine cells. To address this question, we first evaluated FoxO1's role in pancreas development using gain- and loss-of-function alleles in mice. Premature FoxO1 activation in pancreatic progenitors promoted alpha-cell formation but curtailed exocrine development. Conversely, FoxO1 ablation in pancreatic progenitor cells, but not in committed endocrine progenitors or terminally differentiated beta cells, selectively increased juxtaductal beta cells. As these data indicate an involvement of FoxO1 in pancreatic lineage determination, FoxO1(+) Ins(-) cells were clonally isolated and assayed for their capacity to undergo endocrine differentiation. Upon FoxO1 activation, FoxO1(+) Ins(-) cultures converted into glucagon-producing cells. We conclude that FoxO1(+) Ins(-) juxtaductal cells represent a hitherto-unrecognized pancreatic cell population with in vitro capability of endocrine differentiation. C1 [Kitamura, Tadahiro; Kitamura, Yukari Ido; Accili, Domenico] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Kitamura, Tadahiro; Kitamura, Yukari Ido; Kobayashi, Masaki; Kikuchi, Osamu; Sasaki, Tsutomu] Gunma Univ, Metab Signal Res Ctr, Inst Mol & Cellular Regulat, Gunma 3718512, Japan. [DePinho, Ronald A.] Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dept Med, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dept Genet, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Innovat Canc Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Accili, D (reprint author), 1150 St Nicholas Ave, New York, NY 10032 USA. EM da230@columbia.edu FU NIH [DK64819, DK63608]; Russell Berrie Program in Cell-Based Therapies at Columbia University; Robert A. and Renee E. Belfer Family Institute for Innovative Cancer Science FX This work was supported by NIH grants DK64819 and DK63608 (Columbia Diabetes & Endocrinology Research Center) and by the Russell Berrie Program in Cell-Based Therapies at Columbia University. R. A. D. is an American Cancer Society Research Professor and an Ellison Medical Foundation Senior Scholar and is supported by the Robert A. and Renee E. Belfer Family Institute for Innovative Cancer Science. NR 50 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG 15 PY 2009 VL 29 IS 16 BP 4417 EP 4430 DI 10.1128/MCB.01622-08 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 474UP UT WOS:000268310000007 PM 19506018 ER PT J AU Kawada, K Upadhyay, G Ferandon, S Janarthanan, S Hall, M Vilardaga, JP Yajnik, V AF Kawada, Kenji Upadhyay, Geeta Ferandon, Sebastien Janarthanan, Sailajah Hall, Matthew Vilardaga, Jean-Pierre Yajnik, Vijay TI Cell Migration Is Regulated by Platelet-Derived Growth Factor Receptor Endocytosis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PDGF BETA-RECEPTOR; SIGNAL-TRANSDUCTION; NUCLEOTIDE EXCHANGE; BINDING PROTEIN; MEMBRANE; GRB2; DOCK180; INHIBITION; ENDOSOMES; DYNAMIN AB Cell migration requires spatial and temporal processes that detect and transfer extracellular stimuli into intracellular signals. The platelet-derived growth factor (PDGF) receptor is a cell surface receptor on fibroblasts that regulates proliferation and chemotaxis in response to PDGF. How the PDGF signal is transmitted accurately through the receptor into cells is an unresolved question. Here, we report a new intracellular signaling pathway by which DOCK4, a Rac1 guanine exchange factor, and Dynamin regulate cell migration by PDGF receptor endocytosis. We showed by a series of biochemical and microscopy techniques that Grb2 serves as an adaptor protein in the formation of a ternary complex between the PDGF receptor, DOCK4, and Dynamin, which is formed at the leading edge of cells. We found that this ternary complex regulates PDGF-dependent cell migration by promoting PDGF receptor endocytosis and Rac1 activation at the cell membrane. This study revealed a new mechanism by which cell migration is regulated by PDGF receptor endocytosis. C1 [Kawada, Kenji; Upadhyay, Geeta; Janarthanan, Sailajah; Hall, Matthew; Yajnik, Vijay] Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. [Ferandon, Sebastien; Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Ferandon, Sebastien; Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Ctr Syst Biol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Med Ctr, Pittsburgh, PA 15213 USA. RP Yajnik, V (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, GRJ 825,55 Fruit St, Boston, MA 02114 USA. EM vyajnik@partners.org FU NIH [DK 63933]; MGH GI unit startup funds FX This work was supported in part by NIH DK 63933 and MGH GI unit startup funds. NR 37 TC 36 Z9 37 U1 2 U2 2 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 AUG 15 PY 2009 VL 29 IS 16 BP 4508 EP 4518 DI 10.1128/MCB.00015-09 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 474UP UT WOS:000268310000014 PM 19528233 ER PT J AU Little, KY Ramssen, E Welchko, R Volberg, V Roland, CJ Cassin, B AF Little, Karley Y. Ramssen, Eric Welchko, Ryan Volberg, Vitaly Roland, Courtney J. Cassin, Bader TI Decreased brain dopamine cell numbers in human cocaine users SO PSYCHIATRY RESEARCH LA English DT Article DE Cocaine; Dopamine; Neurotoxicity; Dopamine transporter; Cocaine dependence; Parkinson's Disease ID VESICULAR MONOAMINE TRANSPORTER; SUBSTANTIA-NIGRA; PARKINSONS-DISEASE; STRIATAL DOPAMINE; BINDING-SITES; METHAMPHETAMINE USERS; RADIOLIGAND BINDING; OVERDOSE VICTIMS; MPTP TREATMENT; NEURONS AB Cocaine use diminishes striatal and midbrain dopamine neuronal components in both post-mortem and in vivo human experiments. The diffuse nature of these declines suggests the possibility that cocaine use might cause a loss of dopamine neurons in humans. Previous rodent studies have not detected cocaine-induced dopamine cell damage. The present experiment involved counting midbrain dopamine neurons utilizing both melanin and tyrosine hydroxylase immunoreactivity. Well-preserved blocks ranging from + 38 torn obex to +45 mm obex were examined in 10 cocaine users and 9 controls. Sections were also examined for signs of acute pathological injury by counting activated macrophages and microglia. Melanized cells at six midbrain levels were significantly reduced in cocaine users by both drug exposures. The estimated total number of melanized dopamine cells in the anterior midbrain was significantly reduced in cocaine users by 16%. Results with tyrosine hydroxylase immunoreactivity were less conclusive because of variability in staining. Both activated macrophages and activated microglia were significantly increased among cocaine users. Cocaine exposure may have neurotoxic effects on dopamine neurons in humans. The infiltration of phagocytic cells suggests that the lower number of dopamine cells found in cocaine users was a relatively recent effect. The loss of dopamine cells could contribute to and intensify cocaine dependence, as well as anhedonic and depressive symptoms, in some cocaine users. Further efforts at clarifying the pathophysiological mechanisms involved may help explain treatment refractoriness, and identify targets for therapeutic intervention. Published by Elsevier Ireland Ltd. C1 [Little, Karley Y.; Ramssen, Eric; Welchko, Ryan; Volberg, Vitaly; Roland, Courtney J.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Little, Karley Y.] Houston VAMC, Houston, TX USA. [Cassin, Bader] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. RP Little, KY (reprint author), Michael E Debakey Vet Adm Med Ctr, Lab Affect Neuropharmacol 151, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM karleyl@bcm.edu FU NIH [DA15509] FX The research reported was supported by NIH DA15509. NR 71 TC 34 Z9 35 U1 2 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD AUG 15 PY 2009 VL 168 IS 3 BP 173 EP 180 DI 10.1016/j.psychres.2008.10.034 PG 8 WC Psychiatry SC Psychiatry GA 485KB UT WOS:000269118700001 PM 19233481 ER PT J AU Hellner, K Mar, J Fang, F Quackenbush, J Munger, K AF Hellner, Karin Mar, Jessica Fang, Frank Quackenbush, John Muenger, Karl TI HPV16 E7 oncogene expression in normal human epithelial cells causes molecular changes indicative of an epithelial to mesenchymal transition SO VIROLOGY LA English DT Article DE EMT; HPV16; Cervical cancer; E7; E6 ID HUMAN-PAPILLOMAVIRUS TYPE-16; RETINOBLASTOMA TUMOR-SUPPRESSOR; E-CADHERIN EXPRESSION; CERVICAL-CANCER; HUMAN KERATINOCYTES; DNA METHYLATION; GENE-PRODUCT; N-CADHERIN; ONCOPROTEIN; E6 AB Cancer-associated epithelial to mesenchymal transition (EMT) is crucial for invasion and metastasis. Molecular hallmarks of EMT include down-regulation of the epithelial adhesion protein E-cadherin and denovo expression of N-cadherin and the mesenchymal intermediate filament proteins vimentin and fibronectin. Expression of HPV16 E7 in normal human epithelial cells caused increased levels of vimentin and fibronectin, whereas the epithelial adhesion protein E-cadherin was expressed at decreased levels. Similar expression patterns of vimentin. fibronectin and E-cadherin were also detected in cells expressing HPV16 E6 and E7 or the entire HPV16 early transcriptional unit. HPV16 E6 and E7 were each able to induce N-cadherin expression. Interestingly, these changes in expression levels of EMT-associated proteins are not similarly reflected at the level of mRNA expression, Suggesting that HPV16 oncoproteins also modulate EMT through non-transcriptional mechanisms. Hence, HPV16 oncoproteins may contribute to malignant progression through EMT induction. (C) 2009 Elsevier Inc. All rights reserved. C1 [Hellner, Karin; Fang, Frank; Muenger, Karl] Brigham & Womens Hosp, Channing Lab, Div Infect Dis, Boston, MA 02115 USA. [Hellner, Karin; Fang, Frank; Muenger, Karl] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Mar, Jessica; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Munger, K (reprint author), Brigham & Womens Hosp, Channing Lab, Div Infect Dis, Room 861,181 Longwood Ave, Boston, MA 02115 USA. EM kmunger@rics.bwh.harvard.edu OI Munger, Karl/0000-0003-3288-9935 FU PHS [HG004233, CA081135, CA06698]; Deutsche Forschungsgerneinschaft [DFG HE5494/1-1] FX We thank Amy Baldwin for advice with generating HPV16 oncogene expressing keratinocyte cultures, Kristina M. Holton and Renee Rubio for assistance in generating microarray data, Adrian Marino-Enriquez for technical advice and Margaret E. McLaughlin-Drubin for helpful suggestions on this manuscript. We also thank the two anonymous reviewers for their constructive criticisms on an earlier version of this manuscript. KM and KH gratefully acknowledge the invaluable support of Kay Feenby-Skcubrats throughout this study. Supported by PHS grants HG004233 (JQ, KM), CA081135 (KM) and CA06698 (KM). KH was supported by a postdoctoral fellowship from the Deutsche Forschungsgerneinschaft (DFG HE5494/1-1). NR 53 TC 38 Z9 42 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 2009 VL 391 IS 1 BP 57 EP 63 DI 10.1016/j.virol.2009.05.036 PG 7 WC Virology SC Virology GA 482DA UT WOS:000268863000008 PM 19552933 ER PT J AU Torimiro, JN Javanbakht, H Diaz-Griffero, F Kim, J Carr, JK Carrington, M Sawitzke, J Burke, DS Wolfe, ND Dean, M Sodroski, J AF Torimiro, Judith N. Javanbakht, Hassan Diaz-Griffero, Felipe Kim, Jonghwa Carr, Jean K. Carrington, Mary Sawitzke, Julie Burke, Donald S. Wolfe, Nathan D. Dean, Michael Sodroski, Joseph TI A rare null allele potentially encoding a dominant-negative TRIM5 alpha protein in Baka pygmies SO VIROLOGY LA English DT Article DE HIV-1; Susceptibility; Restriction factor; Cross-species transmission; Polymorphism; Mutant; Africa ID SIMIAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; RESTRICTION FACTOR TRIM5-ALPHA; HIV-1 GROUP-O; RETROVIRAL RESTRICTION; GENETIC DIVERSITY; SOOTY MANGABEYS; OLD-WORLD; B30.2(SPRY) DOMAIN; B30.2/SPRY DOMAIN AB The global acquired immunodeficiency syndrome (AIDS) pandemic is thought to have arisen by the transmission of human immunodeficiency virus (HIV-1)-like viruses from chimpanzees in southeastern Cameroon to humans. TRIM5 alpha is a restriction factor that can decrease the susceptibility of cells of particular mammalian species to retrovirus infection. A survey of TRIM5 genes in 127 indigenous individuals from southeastern Cameroon revealed that approximately 4% of the Baka pygmies studied were heterozygous for a rare variant with a stop codon in exon 8. The predicted product Of this allele, TRIM5 R332X, is truncated in the functionally important B30.2(SPRY) domain, does not restrict retrovirus infection, and acts as a dominant-negative inhibitor of wild-type human TRIM5 alpha. Thus, some indigenous African forest dwellers potentially exhibit diminished TRIM5 alpha function; such genetic factors, along with the high frequency of exposure to chimpanzee body fluids, may have predisposed to the initial cross-species transmission of HIV-1-like viruses. (C) 2009 Elsevier Inc. All rights reserved. C1 [Dean, Michael] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. [Torimiro, Judith N.] Univ Yaounde 1, Fac Med & Biomed Sci, Dept Biochem & Physiol Sci, Yaounde, Cameroon. [Torimiro, Judith N.] Chantal Biya Int Reference Ctr, Yaounde, Cameroon. [Javanbakht, Hassan; Diaz-Griffero, Felipe; Kim, Jonghwa; Sodroski, Joseph] Harvard Univ, Sch Med, Div AIDS, Dana Farber Canc Inst,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Carr, Jean K.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Carrington, Mary; Sawitzke, Julie] NCI, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. [Burke, Donald S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Wolfe, Nathan D.] Global Viral Forecasting Initiat, San Francisco, CA 94105 USA. [Wolfe, Nathan D.] Stanford Univ, Program Human Biol, Stanford, CA 94305 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Dean, M (reprint author), NCI, Canc & Inflammat Program, Bldg 560,Room 21-18, Frederick, MD 21702 USA. EM dean@ncifcrf.gov RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU Fogarty International Center/USNIH [2 D 43 TW000010-16 - AITRP]; National Institutes of Health [AI063987, AI076094, AI067854]; Center for AIDS Research Award [AI060354]; International AIDS Vaccine Initiative; Global Viral Forecasting Initiative; William F. McCarty-Cooper; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We thank Ms. Yvette McLaughlin and Ms. Elizabeth Carpelan for the preparation of the manuscript. This work has been Supported, in part, by a Fellowship/Grant from the Fogarty International Center/USNIH: Grant # 2 D 43 TW000010-16 - AITRP; by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center, for Cancer Research: by the National Institutes of Health (AI063987,AI076094, AI067854 and a Center for AIDS Research Award AI060354); by the International AIDS Vaccine Initiative; by the Global Viral Forecasting Initiative; and by the late William F. McCarty-Cooper. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 83 TC 5 Z9 5 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 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 2009 VL 391 IS 1 BP 140 EP 147 DI 10.1016/j.virol.2009.05.038 PG 8 WC Virology SC Virology GA 482DA UT WOS:000268863000017 PM 19577266 ER PT J AU Kajiya, M Silva, MJB Sato, K Ouhara, K Kawai, T AF Kajiya, Mikihito Silva, Marcelo J. B. Sato, Kimihiro Ouhara, Kazuhisa Kawai, Toshihisa TI Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Molecular hydrogen; Colitis; Inflammation; Antioxidant; Colon; Dextran sodium sulfate; IL-12; TNF-alpha; IL-1-beta; Macrophages ID NECROSIS-FACTOR-ALPHA; INDUCED COLITIS; BOWEL-DISEASE; INTESTINAL INFLAMMATION; OXIDATIVE STRESS; MICE; INHALATION; THERAPY; INJURY; MODEL AB By its antioxidant effect, molecular hydrogen gas (H(2)) was reported to protect organs from tissue damage induced by ischemia reperfusion. To evaluate its anti-inflammatory effects, we established a mouse model of human inflammatory bowel disease (IBD) by supplying mice with water containing (1) dextran sodium sulfate (DSS) (5%), (2) DSS (5%) and H(2), or (3) H(2) only ad libitum up to 7 days. At day-7, DSS-induced pathogenic outcomes including, loss of body weight, increase of colitis score, pathogenic shortening of colon length, elevated level of IL-12. TNF-alpha and IL-1 beta in colon lesion, were significantly suppressed by the addition of H(2) to DSS solution. Histological analysis also revealed that the DSS-mediated colonic tissue destruction accompanied by macrophage infiltration was remarkably suppressed by H(2). Therefore, the present study indicated that H(2) can prevent the development of DSS-induced colitis in mice. (C) 2009 Elsevier Inc. All rights reserved. C1 [Kajiya, Mikihito; Silva, Marcelo J. B.; Ouhara, Kazuhisa; Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. [Sato, Kimihiro] Skyview Enterprises, New York, NY USA. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. EM tkawai@forsyth.org RI Silva, Marcelo/J-4298-2012 OI Silva, Marcelo/0000-0002-5807-4286 FU Skyview Enterprises FX We thank Dr. James G. Fox (Division of Comparative Medicine and Biological Engineering, Massachusetts Institute of Technology, Boston, MA) for his cooperation in designing of animal protocol used this study. This study was supported by a research grant from Skyview Enterprises. NR 30 TC 66 Z9 77 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 14 PY 2009 VL 386 IS 1 BP 11 EP 15 DI 10.1016/j.bbrc.2009.05.117 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 469BB UT WOS:000267868800003 PM 19486890 ER PT J AU Stoeckel, LE Kim, J Weller, RE Cox, JE Cook, EW Horwitz, B AF Stoeckel, Luke E. Kim, Jieun Weller, Rosalyn E. Cox, James E. Cook, Edwin W., III Horwitz, Barry TI Effective connectivity of a reward network in obese women SO BRAIN RESEARCH BULLETIN LA English DT Article DE Connectivity; Food cues; Obesity; Reward system ID POSITRON-EMISSION-TOMOGRAPHY; VENTRAL TEGMENTAL AREA; ORBITOFRONTAL CORTEX; NUCLEUS-ACCUMBENS; NEURAL SYSTEMS; BASOLATERAL AMYGDALA; TALAIRACH ATLAS; BASAL FOREBRAIN; SUBSTANCE-ABUSE; FOOD-INTAKE AB Exaggerated reactivity to food cues in obese women appears to be mediated in part by a hyperactive reward system that includes the nucleus accumbens, amygdala, and orbitofrontal cortex. The present study used functional magnetic resonance imaging (fMRI) to investigate whether differences between 12 obese and 12 normal-weight women in reward-related brain activation in response to food images can be explained by changes in the functional interactions between key reward network regions. A two-step path analysis/General Linear Model approach was used to test whether there were group differences in network connections between nucleus accumbens, amygdala, and orbitofrontal cortex in response to high- and low-calorie food images. There was abnormal connectivity in the obese group in response to both high- and low-calorie food cues compared to normal-weight controls. Compared to controls, the obese group had a relative deficiency in the amygdala's modulation of activation in both orbitofirontal cortex and nucleus accumbens, but excessive influence of orbitofrontal cortex's modulation of activation in nucleus accumbens. The deficient projections from the amygdala might relate to suboptimal modulation of the affective/emotional aspects of a food's reward value or an associated cue's motivational salience, whereas increased orbitofrontal cortex to nucleus accumbens connectivity might contribute to a heightened drive to eat in response to a food cue. Thus, it is possible that not only greater activation of the reward system, but also differences in the interaction of regions in this network may contribute to the relatively increased motivational value of foods in obese individuals. (C) 2009 Elsevier Inc. All rights reserved. C1 [Stoeckel, Luke E.; Weller, Rosalyn E.; Cox, James E.; Cook, Edwin W., III] Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. [Stoeckel, Luke E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Stoeckel, Luke E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kim, Jieun; Horwitz, Barry] NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA. RP Stoeckel, LE (reprint author), 1 Bowdoin Sq,Suite 701,7th Floor, Boston, MA 02114 USA. EM lstoeckel@partners.org; kimjieun@nidcd.nih.gov; reweller@uab.edu; jecox@uab.edu; ecook@uab.edu; horwitzb@nidcd.nih.gov FU NIH-NIDCD Intramural Research Program; GCRC [M01 RR-00032]; National Center for Research Resources; Procter and Gamble Co.; UAB's Center for the Development of Functional Imaging (CDFI) FX Supported by the NIH-NIDCD Intramural Research Program, the GCRC grant M01 RR-00032 from the National Center for Research Resources, the Procter and Gamble Co., and resources of UAB's Center for the Development of Functional Imaging (CDFI). NR 85 TC 78 Z9 78 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD AUG 14 PY 2009 VL 79 IS 6 BP 388 EP 395 DI 10.1016/j.brainresbull.2009.05.016 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 478UR UT WOS:000268614400008 PM 19467298 ER PT J AU Idkowiak-Baldys, J Baldys, A Raymond, JR Hannun, YA AF Idkowiak-Baldys, Jolanta Baldys, Aleksander Raymond, John R. Hannun, Yusuf A. TI Sustained Receptor Stimulation Leads to Sequestration of Recycling Endosomes in a Classical Protein Kinase C- and Phospholipase D-dependent Manner SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTORS; COUPLED RECEPTORS; PLASMA-MEMBRANE; 5-HYDROXYTRYPTAMINE(2A) RECEPTOR; DOPAMINE TRANSPORTER; ACTIVATED RECEPTOR-1; 5-HT2A RECEPTORS; BETA-II; DESENSITIZATION; ENDOCYTOSIS AB Considerable insight has been garnered on initial mechanisms of endocytosis of plasma membrane proteins and their subsequent trafficking through the endosomal compartment. It is also well established that ligand stimulation of many plasma membrane receptors leads to their internalization. However, stimulus-induced regulation of endosomal trafficking has not received much attention. In previous studies, we showed that sustained stimulation of protein kinase C(PKC) with phorbol esters led to sequestration of recycling endosomes in a juxtanuclear region. In this study, we investigated whether G-protein-coupled receptors that activate PKC exerted effects on endosomal trafficking. Stimulation of cells with serotonin (5-hydroxytryptamine (5-HT)) led to sequestration of the 5-HT receptor(5-HT(2A)R) into a Rab11-positive juxtanuclear compartment. This sequestration coincided with translocation of PKC as shown by confocal microscopy. Mechanistically the observed sequestration of 5-HT2AR was shown to require continuous PKC activity because it was inhibited by pretreatment with classical PKC inhibitor Go6976 and could be reversed by posttreatment with this inhibitor. In addition, classical PKC autophosphorylation was necessary for receptor sequestration. Moreover inhibition of phospholipase D (PLD) activity and inhibition of PLD1 and PLD2 using dominant negative constructs also prevented this process. Functionally this sequestration did not affect receptor desensitization or resensitization as measured by intracellular calcium increase. However, the PKC- and PLD-dependent sequestration of receptors resulted in co-sequestration of other plasma membrane proteins and receptors as shown for epidermal growth factor receptor and protease activated receptor-1. This led to heterologous desensitization of those receptors and diverted their cellular fate by protecting them from agonist-induced degradation. Taken together, these results demonstrate a novel role for sustained receptor stimulation in regulation of intracellular trafficking, and this process requires sustained stimulation of PKC and PLD. C1 [Idkowiak-Baldys, Jolanta; Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Baldys, Aleksander; Raymond, John R.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Baldys, Aleksander; Raymond, John R.] Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, Charleston, SC 29401 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 173 Ashley Ave,POB 250509, Charleston, SC 29425 USA. EM hannun@musc.edu FU National Institutes of Health [HL43707, R01 GM-63909]; Veterans Affairs Merit and Research Enhancement Award Program Awards; American Heart Association [0725358U] FX This work was supported, in whole or in part, by National Institutes of Health Grants HL43707 (to Y. A. H.) and R01 GM-63909 (to J.R.R.). This work was also supported by Veterans Affairs Merit and Research Enhancement Award Program Awards (to J.R.R.), and American Heart Association Mid-Atlantic Affiliate Grant 0725358U (to A. B.). NR 48 TC 24 Z9 25 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 14 PY 2009 VL 284 IS 33 BP 22322 EP 22331 DI 10.1074/jbc.M109.026765 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 481CE UT WOS:000268783700055 PM 19525236 ER PT J AU Johnson, N Cai, DP Kennedy, RD Pathania, S Arora, M Li, YC D'Andrea, AD Parvin, JD Shapiro, GI AF Johnson, Neil Cai, Dongpo Kennedy, Richard D. Pathania, Shailja Arora, Mansi Li, Yu-Chen D'Andrea, Alan D. Parvin, Jeffrey D. Shapiro, Geoffrey I. TI Cdk1 Participates in BRCA1-Dependent S Phase Checkpoint Control in Response to DNA Damage SO MOLECULAR CELL LA English DT Article ID CANCER-CELL-LINES; END RESECTION; IN-VIVO; BRCA1; CYCLE; KINASE; INHIBITOR; APOPTOSIS; CHK1; ATM AB Cdk2 and cdk1 are individually dispensable for cell-cycle progression in cancer cell lines because they are able to compensate for one another. However, shRNA-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated S phase cell-cycle arrest and the phosphorylation of a subset of ATR/ATM targets after DNA damage. Loss of DNA damage-induced checkpoint control was caused by a reduction in formation of BRCA1-containing foci. Mutation of BRCA1 at S1497 and S1189/S1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of BRCA1-containing foci. Abrogation of checkpoint control after cdk1 depletion or inhibition in non-small-cell lung cancer cells sensitized them to DNA-damaging agents. Conversely, reduced cdk1 activity caused more potent G2/M arrest in nontransformed cells and antagonized the response to subsequent DNA damage. Cdk1 inhibition may therefore selectively sensitize BRCA1-proficient cancer cells to DNA-damaging treatments by disrupting BRCA1 function. C1 [Johnson, Neil; Cai, Dongpo; Li, Yu-Chen; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kennedy, Richard D.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Pathania, Shailja] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Arora, Mansi; Parvin, Jeffrey D.] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA. [Arora, Mansi; Parvin, Jeffrey D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu RI Parvin, Jeffrey/C-8955-2009; Kennedy, Richard/J-3489-2012 OI Kennedy, Richard/0000-0003-4737-6163 FU National Institutes of Health (NIH) [R01 CA090687, P50 CA089393, P20 CA090578, CA111480]; Susan G. Komen Post-Doctoral Fellowship [KG080773]; AstraZeneca FX This work was supported by National Institutes of Health (NIH) Grants R01 CA090687, P50 CA089393 (Dana-Farber/Harvard Cancer Center [DF/HCC] Specialized Program of Research Excellence [SPORE] in Breast Cancer) and P20 CA090578 (DF/HCC SPORE in Lung Cancer) (G.I.S.), as well as Susan G. Komen Post-Doctoral Fellowship Award KG080773 (N.J. and G.I.S.), NIH Grant CA111480 (J.D.P.), and an AstraZeneca Sponsored Research Agreement. NR 25 TC 44 Z9 46 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD AUG 14 PY 2009 VL 35 IS 3 BP 327 EP 339 DI 10.1016/j.molcel.2009.06.036 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 487MO UT WOS:000269278900010 PM 19683496 ER PT J AU Huang, WS Zhu, XT Wang, YH Azam, M Wen, D Sundaramoorthi, R Thomas, RM Liu, S Banda, G Lentini, SP Das, S Xu, QH Keats, J Wang, F Wardwell, S Ning, YY Snodgrass, JT Broudy, MI Russian, K Daley, GQ Iuliucci, J Dalgarno, DC Clackson, T Sawyer, TK Shakespeare, WC AF Huang, Wei-Sheng Zhu, Xiaotian Wang, Yihan Azam, Mohammad Wen, David Sundaramoorthi, Raji Thomas, R. Mathew Liu, Shuangying Banda, Geetha Lentini, Scott P. Das, Sasmita Xu, Qihong Keats, Jeff Wang, Frank Wardwell, Scott Ning, Yaoyu Snodgrass, Joseph T. Broudy, Marc I. Russian, Karin Daley, George Q. Iuliucci, John Dalgarno, David C. Clackson, Tim Sawyer, Tomi K. Shakespeare, William C. TI 9-(Arenethenyl)purines as Dual Src/Abl Kinase Inhibitors Targeting the Inactive Conformation: Design, Synthesis, and Biological Evaluation SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; 3-SUBSTITUTED BENZAMIDE DERIVATIVES; ABL TYROSINE KINASE; IN-VITRO ACTIVITY; MUTANT BCR-ABL; DRUG-RESISTANCE; SOLID TUMORS; C-ABL; SRC AB A novel series of potent dual Src/Abl kinase inhibitors based on a 9-(arenethenyl)purine core has been identified. Unlike traditional dual Src/Abl inhibitors targeting the active enzyme conformation, these inhibitors bind to the inactive, DFG-out Conformation of both kinases. Extensive SAR studies led to the discovery of potent and orally bioavailable inhibitors, some of which demonstrated in vivo efficacy. Once-daily oral administration of inhibitor 9i (AP24226) significantly prolonged the survival of mice injected intravenously with wild type Bcr-Abl expressing Ba/F3 cells at a dose of 10 mg/kg. In a separate model, oral administration of 9i to mice bearing subcutaneous xenografts of Src Y527F expressing NIH 3T3 cells elicited dose-dependent tumor shrinkage with complete tumor regression observed at the highest dose. Notably, several inhibitors (e,g., 14a, AP24163) exhibited modest cellular potency (IC(50) = 300-400 nM) against the Bcr-Abl mutant T3151, a variant resistant to all currently marketed therapies for chronic myeloid leukemia. C1 [Huang, Wei-Sheng; Zhu, Xiaotian; Wang, Yihan; Wen, David; Sundaramoorthi, Raji; Thomas, R. Mathew; Liu, Shuangying; Banda, Geetha; Lentini, Scott P.; Das, Sasmita; Xu, Qihong; Keats, Jeff; Wang, Frank; Wardwell, Scott; Ning, Yaoyu; Snodgrass, Joseph T.; Broudy, Marc I.; Russian, Karin; Iuliucci, John; Dalgarno, David C.; Clackson, Tim; Sawyer, Tomi K.; Shakespeare, William C.] ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. [Azam, Mohammad; Daley, George Q.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Biol Chem & Mol Pharma, Boston, MA 02115 USA. [Azam, Mohammad; Daley, George Q.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Huang, WS (reprint author), ARIAD Pharmaceut Inc, 26 Landsdowne St, Cambridge, MA 02139 USA. EM wei-sheng.huang@ariad.com NR 65 TC 15 Z9 15 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 13 PY 2009 VL 52 IS 15 BP 4743 EP 4756 DI 10.1021/jm900166t PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 479LT UT WOS:000268661600019 PM 19572547 ER PT J AU Hoda, MN Singh, I Singh, AK Khan, M AF Hoda, Md Nasrul Singh, Inderjit Singh, Avtar K. Khan, Mushfiquddin TI Reduction of lipoxidative load by secretory phospholipase A2 inhibition protects against neurovascular injury following experimental stroke in rat SO JOURNAL OF NEUROINFLAMMATION LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; NF-KAPPA-B; BLOOD-BRAIN-BARRIER; ARACHIDONIC-ACID; FATTY-ACIDS; CELL-DEATH; GROUP IIA; REDUCES INFLAMMATION; MEDIATED ACTIVATION; OXIDATIVE STRESS AB Background: In animal models, ischemia reperfusion (IR) injury triggers membrane lipid degradation and accumulation of lipoxidative exacerbations in neurovascular unit, leading to blood brain barrier (BBB) damage and neurologic deficits. In this study, we investigated whether impeding membrane lipid breakdown by inhibiting secretory phospholipase A2 (sPLA2) activity reduces BBB leakage, leading to neuroprotection and functional recovery. Methods: Focal cerebral IR injury was induced by middle cerebral artery occlusion (MCAO) in adult male rats. A sPLA2 inhibitor, 7,7-dimethyleicosadienoic acid (DEDA), was administered following IR injury. DEDA-treated animals were compared with vehicle-treated in terms of BBB leakage, edema, infarct volume, and neurological deficit. Membrane lipid degradation and the expression/activity of sPLA2 were also assessed. The role of one of the sPLA2 products, arachidonic acid (AA), on the morphology of the differentiated neuronal cell PC12 was examined by light microscopy. Results: Treatment with DEDA after IR injury not only reduced BBB leakage but also decreased infarct volume and improved neurologic function. The treatment attenuated both the activity of sPLA2 and the levels of sPLA2-derived oxidized products. The metabolites of lipid oxidation/peroxidation, including the protein carbonyl, were reduced as well. The treatment also restored the levels of glutathione, indicating attenuation of oxidative stress. In vitro treatment of PC12 cells with DEDA did not restore the AA-mediated inhibition of neurite formation and the levels of glutathione, indicating that effect of DEDA is up stream to AA release. Conclusion: sPLA2-derived oxidative products contribute to significant neurovascular damage, and treatment with sPLA2 inhibitor DEDA ameliorates secondary injury by reducing exacerbations from lipoxidative stress. C1 [Hoda, Md Nasrul; Singh, Inderjit; Khan, Mushfiquddin] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph J Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA. RP Khan, M (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. EM hoda@musc.edu; singhi@musc.edu; singha@musc.edu; khanm@musc.edu FU NIH [NS-22576, NS-34741, NS37766]; State of South Carolina Spinal Cord Injury Research Fund Board [SCIRF 0406, SCIRF 0506]; National Center for Research Resources [C06 RR018823, C06 RR015455] FX These studies were supported by grants (NS-22576, NS-34741 and NS37766) from the NIH, Veteran Administration merit award and (SCIRF 0406 and SCIRF 0506) from State of South Carolina Spinal Cord Injury Research Fund Board. This work was also supported by the NIH, Grants C06 RR018823 and No C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources. We are grateful to Dr Tom Smith from the MUSC Writing Center for his valuable editing and correction of the manuscript. We would like to thank Ms. Joyce Bryan for procurement of animals and chemicals used in this study. We would also like to thank Dr Shailendra Giri and Anandakumar Shunmugavel for their valuable assistance with the in vitro work NR 63 TC 13 Z9 16 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD AUG 13 PY 2009 VL 6 AR 21 DI 10.1186/1742-2094-6-21 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 495DD UT WOS:000269869200001 PM 19678934 ER PT J AU West, JA Viswanathan, SR Yabuuchi, A Cunniff, K Takeuchi, A Park, IH Sero, JE Zhu, H Perez-Atayde, A Frazier, AL Surani, MA Daley, GQ AF West, Jason A. Viswanathan, Srinivas R. Yabuuchi, Akiko Cunniff, Kerianne Takeuchi, Ayumu Park, In-Hyun Sero, Julia E. Zhu, Hao Perez-Atayde, Antonio Frazier, A. Lindsay Surani, M. Azim Daley, George Q. TI A role for Lin28 in primordial germ-cell development and germ-cell malignancy SO NATURE LA English DT Article ID EMBRYONIC STEM-CELLS; IN-VITRO; TRANSGENIC MICE; DOWN-REGULATION; MOUSE; MICRORNA; LINEAGE; LET-7; SPECIFICATION; METHYLATION AB The rarity and inaccessibility of the earliest primordial germ cells (PGCs) in the mouse embryo thwart efforts to investigate molecular mechanisms of germ-cell specification. stella (also called Dppa3) marks the rare founder population of the germ lineage(1,2). Here we differentiate mouse embryonic stem cells carrying a stella transgenic reporter into putative PGCs in vitro. The Stella(+) cells possess a transcriptional profile similar to embryo-derived PGCs, and like their counterparts in vivo, lose imprints in a time-dependent manner. Using inhibitory RNAs to screen candidate genes for effects on the development of Stella(+) cells in vitro, we discovered that Lin28, a negative regulator of let-7 microRNA processing(3-6), is essential for proper PGC development. Furthermore, we show that Blimp1 (also called Prdm1), a let-7 target and a master regulator of PGCspecification(7-9), can rescue the effect of Lin28 deficiency during PGC development, thereby establishing a mechanism of action for Lin28 during PGC specification. Overexpression of Lin28 promotes formation of Stella(+) cells in vitro and PGCs in chimaeric embryos, and is associated with human germ-cell tumours. The differentiation of putative PGCs from embryonic stem cells in vitro recapitulates the early stages of gamete development in vivo, and provides an accessible system for discovering novel genes involved in germ-cell development and malignancy. C1 [West, Jason A.; Viswanathan, Srinivas R.; Yabuuchi, Akiko; Cunniff, Kerianne; Takeuchi, Ayumu; Park, In-Hyun; Zhu, Hao; Frazier, A. Lindsay; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [West, Jason A.; Viswanathan, Srinivas R.; Yabuuchi, Akiko; Cunniff, Kerianne; Takeuchi, Ayumu; Park, In-Hyun; Zhu, Hao; Frazier, A. Lindsay; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [West, Jason A.; Viswanathan, Srinivas R.; Yabuuchi, Akiko; Cunniff, Kerianne; Takeuchi, Ayumu; Park, In-Hyun; Zhu, Hao; Daley, George Q.] Harvard Univ, Stem Cell Inst, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Sero, Julia E.; Perez-Atayde, Antonio] Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA. [Frazier, A. Lindsay] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Surani, M. Azim] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst Canc & Dev, Cambridge CB2 1QN, England. [Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu RI West, Jason/I-4445-2014; Julia, Sero/J-5476-2016; OI West, Jason/0000-0002-7252-8651; Julia, Sero/0000-0002-0299-9212; Zhu, Hao/0000-0002-8417-9698; Surani, Azim/0000-0002-8640-4318 FU NIH; Harvard Stem Cell Institute; Burroughs Wellcome Fund Clinical Scientist Award in Translational Research FX We thank M. W. Lensch for comments on this manuscript; D. K. Gifford, G. Gerber, C. Reeder and J. Baughman for comments and input regarding microarray analysis; G. Losyev for flow cytometry expertise; and S. Winkler of the British Consulate for providing support for collaboration between the Daley and Surani laboratories. This study was supported by grants from the NIH, the NIH Director's Pioneer Award of the NIH Roadmap for Medical Research, and by support from the germ cell program of the Harvard Stem Cell Institute. G. Q. D. is a recipient of the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research. NR 40 TC 205 Z9 220 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 13 PY 2009 VL 460 IS 7257 BP 909 EP U151 DI 10.1038/nature08210 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 483CB UT WOS:000268938300042 PM 19578360 ER PT J AU Burstein, HJ Souter, I D'Alessandro, HA Sgroi, DC AF Burstein, Harold J. Souter, Irene D'Alessandro, Helen Anne Sgroi, Dennis C. TI A Woman with Hormone-Receptor-Positive Breast Cancer Invasive ductal carcinoma, grade 2 of 3, ER-positive, PR-positive, HER2-negative, T1c pN1mi (stage II). Ductal carcinoma in situ, solid and cribriform types. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Postgraduate Course Breast Cancer - Current Controversies and New Horizons CY JUL 10-12, 2008 CL Boston, MA ID GENE-EXPRESSION SIGNATURES; ADJUVANT ENDOCRINE THERAPY; AMERICAN-JOINT-COMMITTEE; PREMENOPAUSAL WOMEN; OOCYTE CRYOPRESERVATION; OVARIAN STIMULATION; LYMPH-NODES; YOUNG-WOMEN; ESTROGEN; CHEMOTHERAPY C1 [Burstein, Harold J.] Massachusetts Gen Hosp, Div Med Oncol, Dana Farber Canc Inst, Boston, MA 02114 USA. [Burstein, Harold J.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Med, Boston, MA 02114 USA. [Souter, Irene] Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. [D'Alessandro, Helen Anne] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Burstein, Harold J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Souter, Irene] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [D'Alessandro, Helen Anne] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Sgroi, Dennis C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Massachusetts Gen Hosp, Div Med Oncol, Dana Farber Canc Inst, Boston, MA 02114 USA. NR 52 TC 2 Z9 2 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 13 PY 2009 VL 361 IS 7 BP 699 EP 707 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 482JX UT WOS:000268884100012 PM 19675333 ER PT J AU Zechmeister, I de Blasio, BF Garnett, G Neilson, AR Siebert, U AF Zechmeister, Ingrid de Blasio, Birgitte Freiesleben Garnett, Geoff Neilson, Aileen Rae Siebert, Uwe TI Cost-effectiveness analysis of human papillomavirus-vaccination programs to prevent cervical cancer in Austria SO VACCINE LA English DT Article DE HPV-vaccination; Cost-effectiveness; Cervical cancer screening ID ECONOMIC-EVALUATION; HPV VACCINATION; NATURAL-HISTORY; MODEL; TRANSFERABILITY; INFECTION; HEALTH; IMPACT; WOMEN AB Objective: The study predicts long-term cervical cancer related population health and economic effects of introducing the HPV-vaccination for 12-year-old girls (and boys) in addition to current screening compared with screening only. Method: Health effects are predicted by a dynamic transmission model. Model results are used to calculate incremental cost-effectiveness ratios (ICER) in (sic) per life year gained (LYG) for a time-horizon between 2008 and 2060 from a public payer and a societal perspective. Results: Vaccination of girls results a discounted ICER of (sic) 64,000/LYG and (sic) 50,000/LYG from a payer's and societal perspectives respectively. The additional vaccination of boys increases the ICER to (sic) 311,000 and (sic) 299,000/LYG respectively. Results were most sensitive to vaccination price, discount rate and time-horizon. Conclusion: HPV-vaccination for girls should be cost-effective when adopting a longer time-horizon and a societal perspective. Applying a shorter time frame and a payer's perspective or vaccinating boys may not be cost-effective without reducing the vaccine price. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Zechmeister, Ingrid] Ludwig Boltzmann Inst Hlth Technol Assessment, A-1090 Vienna, Austria. [de Blasio, Birgitte Freiesleben] Univ Oslo, Inst Basic Med Sci, Oslo, Norway. [Garnett, Geoff] Univ London Imperial Coll Sci Technol & Med, Inst Microparasite Epidemiol, London, England. [Neilson, Aileen Rae] Norwegian Knowledge Ctr Hlth Serv, Oslo, Norway. [Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Med Decis Making & HTA, Hall In Tirol, LT, Austria. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Decis Sci, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Zechmeister, I (reprint author), Ludwig Boltzmann Inst Hlth Technol Assessment, Garnisongasse 7-20, A-1090 Vienna, Austria. EM Ingrid.zechmeister@hta.lbg.ac.at RI Garnett, Geoffrey/A-9312-2008 NR 45 TC 29 Z9 29 U1 2 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 13 PY 2009 VL 27 IS 37 BP 5133 EP 5141 DI 10.1016/j.vaccine.2009.06.039 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 485ED UT WOS:000269102800016 PM 19567244 ER PT J AU Chan, AT Ogino, S Fuchs, CS AF Chan, Andrew T. Ogino, Shuji Fuchs, Charles S. TI Aspirin Use and Survival After Diagnosis of Colorectal Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Digestive Disease Week/110th Annual Meeting of the American-Gastroenterological-Association CY MAY 30-JUN 04, 2009 CL Chicago, IL SP Amer Gastroenterol Assoc ID CYCLOOXYGENASE-2 GENE-EXPRESSION; FOOD FREQUENCY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; NATIONAL DEATH INDEX; COLON-CANCER; LIVER METASTASIS; RANDOMIZED-TRIAL; UP-REGULATION; HEMATOGENOUS METASTASIS; SELECTIVE-INHIBITION AB Context Aspirin reduces risk of colorectal neoplasia in randomized trials and inhibits tumor growth and metastases in animal models. However, the influence of aspirin on survival after diagnosis of colorectal cancer is unknown. Objective To examine the association between aspirin use after colorectal cancer diagnosis on colorectal cancer-specific and overall survival. Design, Setting, and Participants Prospective cohort study of 1279 men and women diagnosed with stage I, II, or III colorectal cancer. Participants were enrolled in 2 nationwide health professional cohorts in 1980 and 1986 prior to diagnosis and followed up through June 1, 2008. Main Outcome Measure Colorectal cancer-specific and overall mortality. Results After a median follow-up of 11.8 years, there were 193 total deaths (35%) and 81 colorectal cancer-specific deaths (15%) among 549 participants who regularly used aspirin after colorectal cancer diagnosis, compared with 287 total deaths (39%) and 141 colorectal cancer-specific deaths (19%) among 730 participants who did not use aspirin. Compared with nonusers, participants who regularly used aspirin after diagnosis experienced a multivariate hazard ratio (HR) for colorectal cancer-specific mortality of 0.71 (95% confidence interval [CI], 0.53-0.95) and for overall mortality of 0.79 ( 95% CI, 0.65-0.97). Among 719 participants who did not use aspirin before diagnosis, aspirin use initiated after diagnosis was associated with a multivariate HR for colorectal cancer-specific mortality of 0.53 ( 95% CI, 0.33-0.86). Among 459 participants with colorectal cancers that were accessible for immunohistochemical assessment, the effect of aspirin differed significantly according to cyclooxygenase 2 (COX-2) expression (P for interaction = .04). Regular aspirin use after diagnosis was associated with a lower risk of colorectal cancer-specific mortality among participants in whom primary tumors overexpressed COX-2 ( multivariate HR, 0.39; 95% CI, 0.20-0.76), whereas aspirin use was not associated with lower risk among those with primary tumors with weak or absent expression ( multivariate HR, 1.22; 95% CI, 0.36-4.18). Conclusion Regular aspirin use after the diagnosis of colorectal cancer is associated with lower risk of colorectal cancer-specific and overall mortality, especially among individuals with tumors that overexpress COX-2. JAMA. 2009; 302(6):649-659 www.jama.com C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Andrew T.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 722, Boston, MA 02114 USA. EM achan@partners.org FU NCI NIH HHS [CA137178, CA107412, CA118553, CA122826, CA127003, CA55075, CA87969, K07 CA107412, K07 CA107412-05, K07 CA122826, P01 CA055075, P01 CA055075-110002, P01 CA055075-18, P01 CA087969, P50 CA127003, P50 CA127003-03, R01 CA118553, R01 CA118553-03, R01 CA137178, R01 CA137178-01A1] NR 66 TC 255 Z9 264 U1 1 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 12 PY 2009 VL 302 IS 6 BP 649 EP 659 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 481ZI UT WOS:000268852300023 PM 19671906 ER PT J AU Wan, JB Lee, SMY Wang, JD Wang, N He, CW Wang, YT Kang, JX AF Wan, Jian-Bo Lee, Simon Ming-Yuen Wang, Jing-Dong Wang, Nan He, Cheng-Wei Wang, Yi-Tao Kang, Jing X. TI Panax notoginseng Reduces Atherosclerotic Lesions in ApoE-Deficient Mice and Inhibits TNF-alpha-Induced Endothelial Adhesion Molecule Expression and Monocyte Adhesion SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Panax notoginseng; atherosclerosis; inflammation; apoE-deficient mice; adhesion molecules ID APOLIPOPROTEIN-E; LIPID PROFILE; SAPONINS; CELLS; MECHANISMS; DISEASE; PROLIFERATION; RATS; HPLC AB It is widely recognized that atherogenesis is associated with vascular inflammation. Panax notoginseng, a commonly used herb in China, has been shown to possess anti-inflammatory activity. In the present study, the antiatherogenic effect of P. notoginseng saponins (PNS) was examined in apolipoprotein E (apoE)-deficient mice. The molecular mechanisms responsible for the antivascular inflammatory effect of PNS on human coronary artery endothelial cells (HCAECs) were also investigated in vitro. PNS, dissolved in drinking water, was administered orally to two treatment groups at dosages of 4.0 and 12.0 mg/day/mouse, respectively. After 8 weeks, atherosclerosis in the entire aortic area was assessed using an en face method. Compared with the control group, both low- and high-dose PNS-treated groups showed a significant decrease in extent of atherosclerotic lesions by 61.4 and 66.2%, respectively (P < 0.01). PNS also notably reduced serum lipid levels. Serum levels of IL-6 and TNF-alpha in all groups of apoE-deficient mice were below the detection limit. In vitro studies showed that PNS dose-dependently inhibited monocyte adhesion on activated endothelium, as well as the expression of TNF-alpha-induced endothelial adhesion molecules, such as ICAM-1 and VCAM-1. In conclusion, PNS has antiatherogenic activity through, at least in part, its lipid-lowering and antivascular inflammatory mechanisms. C1 [Wan, Jian-Bo; Wang, Jing-Dong; He, Cheng-Wei; Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wan, Jian-Bo; Wang, Jing-Dong; He, Cheng-Wei; Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wan, Jian-Bo; Lee, Simon Ming-Yuen; Wang, Nan; Wang, Yi-Tao] Univ Macau, Inst Chinese Med Sci, Taipa, Macau, Peoples R China. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Room 4433,149 13th St, Charlestown, MA 02129 USA. EM ytwang@umac.mo; kang.jing@mgh.harvard.edu RI Wan, Jian-Bo/D-8368-2014; Wang, Yitao/O-5184-2016 OI Wan, Jian-Bo/0000-0002-6750-2617; NR 28 TC 38 Z9 44 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD AUG 12 PY 2009 VL 57 IS 15 BP 6692 EP 6697 DI 10.1021/jf900529w PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 477RW UT WOS:000268537300030 PM 19722574 ER PT J AU Ai, M Otokozawa, S Schaefer, EJ Asztalos, BF Nakajima, K Shrader, P Kathiresan, S Meigs, JB Williams, G Nathan, DM AF Ai, Masumi Otokozawa, Seiko Schaefer, Ernst J. Asztalos, Bela F. Nakajima, Katsuyuki Shrader, Peter Kathiresan, Sekar Meigs, James B. Williams, Gordon Nathan, David M. TI Glycated albumin and direct low density lipoprotein cholesterol levels in type 2 diabetes mellitus SO CLINICA CHIMICA ACTA LA English DT Article DE Glycated albumin; Low density lipoprotein cholesterol; Type 2 diabetes ID CORONARY-HEART-DISEASE; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR-DISEASE; ALPHA-CYCLODEXTRIN; ATORVASTATIN; SERUM; SIMVASTATIN; PROGRAM; STATINS; PLASMA AB Background: Diabetes mellitus is a major risk factor for coronary heart disease (CND), renal failure, retinopathy. and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the utility of glycated albumin (GA) and direct LDL-C, 2 novel assay, as compared to HbA1c and calculated LDL-C, in evaluating diabetes control and lipid in a heterogeneous population and in specific subgroups of patients with type 2 diabetes mellitus. Methods: We obtained fasting blood samples and measured HbA1c, GA, and direct LDL-C, as well as other parameters, in a multi-ethnic population of 616 male and female patients with type 2 diabetes and 895 nondiabetic controls. Results: HbA1c and GA levels, which measure different periods of glycemia, had a correlation of r = 0.70 (p < 0.001), and mean values in patients were 38.7% and 43.4% higher, respectively, than controls in men, and 41.1% and 40.1% higher, respectively, than controls, in women (both p < 0.001). Calculated and direct LDL-C values correlated very highly (r = 0.96, p < 0.001). The correlations between HbA1c and GA, and between calculated and direct LDL-C were similar for subgroups defined by gender, race, age, and other factors. Conclusions: Calculated LDL-C provides an accurate assessment of fasting LDL-C compared with a direct measurement in most subjects, except for those with hypertriglyceridemia, and GA correlates with HbA1c in diabetic and non-diabetic subjects and may serve as a reasonable marker of short term diabetic control. (C) 2009 Elsevier B.V. All rights reserved. C1 [Ai, Masumi; Otokozawa, Seiko; Schaefer, Ernst J.; Asztalos, Bela F.; Nakajima, Katsuyuki] Tufts Univ, Lipid Metab Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Ai, Masumi; Otokozawa, Seiko; Schaefer, Ernst J.; Asztalos, Bela F.; Nakajima, Katsuyuki] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kathiresan, Sekar; Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Williams, Gordon] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. [Kathiresan, Sekar; Meigs, James B.; Williams, Gordon; Nathan, David M.] Harvard Univ, Sch Med, Boston, MA USA. RP Schaefer, EJ (reprint author), Tufts Univ, Lipid Metab Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. EM Ernst.schaefer@tufts.edu FU Denka-Seiken Corporation; Kyowa-Medex Corporation, Tokyo, Japan; US Department of Agriculture [53-1950-5-003]; National Institutes of Health, Bethesda, MD [HL 74753, HL 60935, PO50HL083813]; American Diabetes Association Career Development Award, Arlington, VA; Ida Charlton Family Trust; Roche Diagnostics Inc, Nutley, NJ FX Dr. Ai and Ms. Otokozawa were supported by research fellowships from the Denka-Seiken Corporation, and the Kyowa-Medex Corporation, Tokyo, Japan, respectively. Dr. Nakajima is a Distinguished Visiting Scientist at Tufts University. Dr. Schaefer is supported by contract 53-1950-5-003 from the US Department of Agriculture, and grants HL 74753 and HL 60935 and project PO50HL083813 from the National Institutes of Health, Bethesda, MD. Dr. Meigs is supported by an American Diabetes Association Career Development Award, Arlington, VA. Dr. Nathan is supported in part by the Ida Charlton Family Trust. The sampling of study subjects was supported in part through a contract with Roche Diagnostics Inc, Nutley, NJ. NR 27 TC 15 Z9 15 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD AUG 11 PY 2009 VL 406 IS 1-2 BP 71 EP 74 DI 10.1016/j.cca.2009.05.015 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 482XM UT WOS:000268923900015 PM 19465013 ER PT J AU Yotsumoto, Y Sasaki, Y Chan, P Vasios, CE Bonmassar, G Ito, N Nanez, JE Shimojo, S Watanabe, T AF Yotsumoto, Yuko Sasaki, Yuka Chan, Patrick Vasios, Christos E. Bonmassar, Giorgio Ito, Nozomi Nanez, Jose E., Sr. Shimojo, Shinsuke Watanabe, Takeo TI Location-Specific Cortical Activation Changes during Sleep after Training for Perceptual Learning SO CURRENT BIOLOGY LA English DT Article ID EXPERIENCE-DEPENDENT CHANGES; PRIMARY VISUAL-CORTEX; SLOW-WAVE SLEEP; MEMORY CONSOLIDATION; TEXTURE-DISCRIMINATION; REM-SLEEP; CONNECTIVITY; REACTIVATION; IMPROVEMENT; PLASTICITY AB Visual perceptual learning is defined as performance enhancement on a sensory task and is distinguished from other types of learning and memory in that it is highly specific for location of the trained stimulus. The location specificity has been shown to be paralleled by enhancement in functional magnetic resonance imaging (fMRI) signal in the trained region of V1 [1-3] after visual training. Although recently the role of sleep in strengthening visual perceptual learning has attracted much attention, its underlying neural mechanism has yet to be clarified. Here, for the first time, fMRI measurement of human V1 activation was conducted concurrently with a polysomnogram during sleep with and without preceding training for visual perceptual learning. As a result of predetermined region-of-interest analysis of Vi, activation enhancement during non-rapid-eye-movement sleep after training was observed specifically in the trained region of Vi. Furthermore, improvement of task performance measured subsequently to the post-training sleep session was significantly correlated with the amount of the trained-region-specific fMRI activation in Vi during sleep. These results suggest that as far as V1 is concerned, only the trained region is involved in improving task performance after sleep. C1 [Yotsumoto, Yuko; Sasaki, Yuka; Chan, Patrick; Vasios, Christos E.; Bonmassar, Giorgio] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Yotsumoto, Yuko; Chan, Patrick; Ito, Nozomi; Watanabe, Takeo] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Nanez, Jose E., Sr.] Arizona State Univ, Dept Social & Behav Sci, Phoenix, AZ 85069 USA. [Sasaki, Yuka; Shimojo, Shinsuke] NTT Corp, NTT, Shimojo Implicit Brain Funct Project, ERATO,Commun Sci Labs, Atsugi, Kanagawa 2430198, Japan. [Shimojo, Shinsuke] CALTECH, Div Biol Opt Representat Computat & Neural Syst, Pasadena, CA 91125 USA. [Yotsumoto, Yuko; Sasaki, Yuka; Vasios, Christos E.; Bonmassar, Giorgio] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Sasaki, Y (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. EM yuka@nmr.mgh.harvard.edu; takeo@bu.edu FU National Eye Institutes [R21EY018925, R01EY019466, R01EY015980]; National Institutes of Health National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery (MIND) Institute; Japan Science and Technology; Japan Society for the Promotion of Science FX This work was supported by the National Eye Institutes (R21EY018925, R01EY019466, and R01EY015980), the National Institutes of Health National Center for Research Resources (P41RR14075), the Mental Illness and Neuroscience Discovery (MIND) Institute, the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, the ERATO Shimojo Implicit Brain Function Project from Japan Science and Technology, and the Japan Society for the Promotion of Science. The authors thank Patrick Purdon and Leonardo Angelone for assistance in simultaneous EEG and fMRI measurements and Kristina Vissher and Aaron Seitz for helpful comments. NR 28 TC 59 Z9 60 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 11 PY 2009 VL 19 IS 15 BP 1278 EP 1282 DI 10.1016/j.cub.2009.06.011 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 482WT UT WOS:000268921900023 PM 19576772 ER PT J AU Billings, CJ Tremblay, KL Stecker, GC Tolin, WM AF Billings, Curtis J. Tremblay, Kelly L. Stecker, G. Christopher Tolin, Wendy M. TI Human evoked cortical activity to signal-to-noise ratio and absolute signal level SO HEARING RESEARCH LA English DT Article DE Cortical auditory evoked potentials (CAEPs); Event-related potentials (ERPs); Signals in noise; Signal-to-noise ratio (SNR); N1; Auditory cortex; Hearing aids ID SENSORINEURAL HEARING-LOSS; EVENT-RELATED POTENTIALS; BROAD-BAND NOISE; NEURAL REPRESENTATION; AUDITORY-CORTEX; BEHAVIORAL MEASURES; STIMULUS-INTENSITY; AMPLIFIED SPEECH; RESPONSES; SOUND AB The purpose of this study was to determine the effect of signal level and signal-to-noise ratio (SNR) on the latency and amplitude of evoked cortical activity to further our understanding of how the human central auditory system encodes signals in noise. Cortical auditory evoked potentials (CAEPs) were recorded from 15 young normal-hearing adults in response to a 1000 Hz tone presented at two tone levels in quiet and while continuous background noise levels were varied in five equivalent SNR steps. These 12 conditions were used to determine the effects of signal level and SNR level on CAEP components P1, N1, P2, and N2. Based on prior signal-in-noise experiments conducted in animals, we hypothesized that SNR, would be a key contributor to human CAEP characteristics. As hypothesized, amplitude increased and latency decreased with increasing SNR; in addition, there was no main effect of tone level across the two signal levels tested (60 and 75 dB SPL). Morphology of the P1-N1-P2 complex was driven primarily by SNR, highlighting the importance of noise when recording CAEPs. Results are discussed in terms of the current interest in recording CAEPs in hearing aid users. Published by Elsevier B.V. C1 [Billings, Curtis J.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. [Billings, Curtis J.; Tremblay, Kelly L.; Stecker, G. Christopher; Tolin, Wendy M.] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98105 USA. RP Billings, CJ (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM curtis.billings2@va.gov; tremblay@u.washington.edu; cstecker@u.washington.edu; wendyt3@u.washington.edu FU National Institutes of Health through the National Institute on Deafness and Other Communication Disorders [F31-DC007296, R01-DC007705, P30DC004661] FX The authors thank Richard Folsom and Pamela Souza who contributed to this work through many helpful discussions and as dissertation committee members of the first author. The authors are also grateful to the reviewers for their helpful comments. This work was supported by the National Institutes of Health through the National Institute on Deafness and Other Communication Disorders (F31-DC007296, CJ.B.; R01-DC007705, K.L.T.; P30DC004661). NR 59 TC 37 Z9 43 U1 3 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD AUG 11 PY 2009 VL 254 IS 1-2 BP 15 EP 24 DI 10.1016/j.heares.2009.04.002 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 476KH UT WOS:000268438500002 PM 19364526 ER PT J AU Hochberg, FH Rodriguez, FJ Atkinson, JLD Shaw, EG Keegan, BM Kantarci, OH AF Hochberg, F. H. Rodriguez, F. J. Atkinson, J. L. D. Shaw, E. G. Keegan, B. M. Kantarci, O. H. TI A 54-year-old woman with progressive gait disturbance and MRI abnormalities SO NEUROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; OF-THE-LITERATURE; PRIMARY CNS LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; LANGERHANS CELL HISTIOCYTOSIS; POLYMERASE-CHAIN-REACTION; MULTIPLE-SCLEROSIS; CONJUNCTIVAL BIOPSY; SUSACS-SYNDROME; CEREBRAL METASTASES C1 [Keegan, B. M.; Kantarci, O. H.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. [Hochberg, F. H.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Dept Neurol, Boston, MA USA. [Rodriguez, F. J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Atkinson, J. L. D.] Mayo Clin, Dept Neurosurg, Rochester, MN 55905 USA. [Shaw, E. G.] Wake Forest Univ, Baptist Med Ctr, Dept Radiat Oncol, Winston Salem, NC 27109 USA. RP Kantarci, OH (reprint author), Mayo Clin, Dept Neurol, 200 1st St SW, Rochester, MN 55905 USA. EM kantarci.orhun@mayo.edu NR 76 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 11 PY 2009 VL 73 IS 6 BP 466 EP 474 DI 10.1212/WNL.0b013e3181b1644d PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 481LV UT WOS:000268813500010 PM 19667322 ER PT J AU Lopez, L Hicks, LS Cohen, AP McKean, S Weissman, JS AF Lopez, Lenny Hicks, Leroi S. Cohen, Amy P. McKean, Sylvia Weissman, Joel S. TI Hospitalists and the Quality of Care in Hospitals SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Conference of the Society-of-Hospital-Medicine CY APR 03, 2008 CL San Diego, CA SP Soc Hosp Med ID ACUTE MYOCARDIAL-INFARCTION; HEART-FAILURE; US HOSPITALS; PERFORMANCE-MEASURES; MORTALITY-RATES; UNITED-STATES; OUTCOMES; IMPACT; PHYSICIANS; ASSOCIATION AB Background: Little is known about the link between hospitalists and performance on hospital-level quality indicators. Methods: From October 1, 2005, through September 31, 2006, we linked the Hospital Quality Alliance (HQA) data to the American Hospital Association data on the presence of hospitalists. Main outcome measures included composite measurements of hospital-level quality of care for 3 conditions (acute myocardial infarction [AMI], congestive heart failure [CHF], and pneumonia) and 2 dimensions of care (treatment and diagnosis, as well as counseling and prevention). We fitted a series of logistic regression models to examine the relationship between hospitalists and overall quality of care for each condition, controlling for all other hospital characteristics. Results: Of 3619 hospitals reporting HQA data, 1461 (40.4%) had hospitalists. Hospitals with hospitalists tended to be large, private, not-for-profit, teaching institutions located in the southern United States. The mean unadjusted composite scores were higher for hospitals with hospitalists vs those with no hospitalists for all 3 conditions (93% vs 86% for AMI, 82% vs 72% for CHF, and 75% vs 71% for pneumonia) and.both dimensions of care (87% vs 77% for treatment and diagnosis and 75% vs 66% for counseling and prevention) (P < .001 for all comparisons). After multivariable adjustment, hospitals with hospitalists continued to perform significantly better than those without hospitalists across all composite scores except for CHF. Conclusion: Hospitals with hospitalists were associated with better performance on HQA indicators for AMI, pneumonia, and the domains of overall disease treatment and diagnosis, as well as counseling and prevention. C1 [Lopez, Lenny; Weissman, Joel S.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny; Weissman, Joel S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lopez, Lenny; Hicks, Leroi S.; McKean, Sylvia] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Lopez, Lenny; Hicks, Leroi S.; McKean, Sylvia] Brigham & Womens Hosp, Acad Hospitalist Program, Boston, MA 02115 USA. [Cohen, Amy P.; Weissman, Joel S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hicks, Leroi S.; Weissman, Joel S.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Lopez, Lenny; Hicks, Leroi S.; McKean, Sylvia; Weissman, Joel S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Lopez, L (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM llopez1@partners.org FU PHS HHS [5 T32 HP11001-19] NR 33 TC 12 Z9 13 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 10 PY 2009 VL 169 IS 15 BP 1389 EP 1394 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 481HJ UT WOS:000268798100009 PM 19667302 ER PT J AU Wiklund, F Tretli, S Choueiri, TK Signoretti, S Fall, K Adami, HO AF Wiklund, Fredrik Tretli, Steinar Choueiri, Toni K. Signoretti, Sabina Fall, Katja Adami, Hans-Olov TI Risk of Bilateral Renal Cell Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER; CARCINOMA; PROGNOSIS; TUMORS AB Purpose The risk of developing bilateral kidney cancer has not been adequately defined in any large, population-based study with long-term follow-up to our knowledge. Patients and Methods We estimated the risk of metachronous bilateral renal cell cancer in patients diagnosed with unilateral kidney cancer, as recorded in the nationwide cancer registries of Norway and Sweden. Altogether 28,642 patients were followed for an average of 4.4 years. The standardized incidence ratio-the ratio of the observed number of bilateral cancers to the number expected on the basis of the incidence in the Norwegian and Swedish population at large-was used as a measure of relative risk. We used multivariate Poisson regression to separate the effects of the explanatory variables. Results A synchronous bilateral renal cell cancer was reported in 86 patients. A total of 112 metachronous bilateral cancers were recorded during 126,493 person-years of follow-up compared with 35.8 expected, yielding an overall relative risk (RR) of 3.1 (95% CI, 2.6 to 3.8) and a cumulative incidence of 0.8% after 20 or more years of follow-up. In the multivariate analyses, risk increased monotonically with younger age at first diagnosis (P for trend <.001); compared with patients who were 60 years or older, those younger than 40 years were at a 17-fold higher risk (RR = 17.4; 95% CI, 10.1 to 29.8). We also found a modest but statistically significant decreasing trend with increasing duration of follow-up. Conclusion The risk of metachronous bilateral renal cell cancer is drastically higher among patients first affected at a young age, suggesting a subset of early onset renal cell cancer with a strong genetic component. C1 [Adami, Hans-Olov] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Canc Registry Norway, Oslo, Norway. Dana Farber Canc Inst, Boston, MA USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Adami, HO (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM adami@hsph.harvard.edu RI Fall, Katja/A-9186-2012; OI Fall, Katja/0000-0002-3649-2639 NR 16 TC 20 Z9 22 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2009 VL 27 IS 23 BP 3737 EP 3741 DI 10.1200/JCO.2008.20.6524 PG 5 WC Oncology SC Oncology GA 480XF UT WOS:000268769900004 PM 19597028 ER PT J AU Poplin, E Feng, Y Berlin, J Rothenberg, ML Hochster, H Mitchell, E Alberts, S O'Dwyer, P Haller, D Catalano, P Cella, D Benson, AB AF Poplin, Elizabeth Feng, Yang Berlin, Jordan Rothenberg, Mace L. Hochster, Howard Mitchell, Edith Alberts, Steven O'Dwyer, Peter Haller, Daniel Catalano, Paul Cella, David Benson, Al Bowen, III TI Phase III, Randomized Study of Gemcitabine and Oxaliplatin Versus Gemcitabine (fixed-dose rate infusion) Compared With Gemcitabine (30-minute infusion) in Patients With Pancreatic Carcinoma E6201: A Trial of the Eastern Cooperative Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PLUS GEMCITABINE; CANCER; COMBINATION; SURVIVAL; THERAPY AB Purpose Single-agent gemcitabine (GEM) is standard treatment of metastatic pancreatic cancer. Fixed-dose rate (FDR) GEM and GEM plus oxaliplatin have shown promise in early clinical trials. E6201 was designed to compare overall survival (OS) of standard weekly GEM 1,000 mg/m(2)/30 minutes versus GEM FDR 1,500 mg/m(2)/150 minutes or GEM 1,000 mg/m(2)/100 minutes/day 1 plus oxaliplatin 100 mg/m(2)/day 2 every 14 days (GEMOX). Methods This trial included patients with metastatic or locally advanced pancreatic cancer, normal organ function, and performance status of 0 to 2. The study was designed to detect a 33% difference in median survival (hazard ratio [HR] <= 0.75 for either of the experimental arms) with 81% power while maintaining a significance level of 2.5% in a two-sided test for each of the two primary comparisons. Results Eight hundred thirty-two patients were enrolled. The median survival and 1-year survival were 4.9 months (95% CI, 4.5 to 5.6) and 16% for GEM, 6.2 months (95% CI, 5.4 to 6.9), and 21% for GEM FDR (HR, 0.83; stratified log-rank P = .04), and 5.7 months (95% CI, 4.9 to 6.5) and 21% for GEMOX (HR, 0.88; stratified log-rank P = .22). Neither of these differences met the prespecified criteria for significance. Survival was 9.2 months for patients with locally advanced disease, and 5.4 months for those with metastatic disease. Grade 3/4 neutropenia and thrombocytopenia were greatest with GEM FDR. GEMOX caused higher rates of nausea, vomiting, and neuropathy. Conclusion Neither GEM FDR nor GEMOX resulted in substantially improved survival or symptom benefit over standard GEM in patients with advanced pancreatic cancer. C1 [Poplin, Elizabeth] Canc Inst New Jersey, New Brunswick, NJ 08903 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Pfizer, New York, NY USA. NYU, Inst Canc, New York, NY USA. Thomas Jefferson Univ, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Mayo Clin, Rochester, MN USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Poplin, E (reprint author), Canc Inst New Jersey, 195 Little Albany St, New Brunswick, NJ 08903 USA. EM poplinea@umdnj.edu FU National Cancer Institute [CA23318, CA66636, CA21115, CA25224, CA17145]; National Institutes of Health; Department of Health and Human Services FX This study was coordinated by the Eastern Cooperative Oncology Group (Robert L. Comis), and supported in part by Public Health Service Grants No. CA23318, CA66636, CA21115, CA25224 and CA17145 from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 25 TC 235 Z9 244 U1 1 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2009 VL 27 IS 23 BP 3778 EP 3785 DI 10.1200/JCO.2008.20.9007 PG 8 WC Oncology SC Oncology GA 480XF UT WOS:000268769900010 PM 19581537 ER PT J AU Schlumberger, MJ Elisei, R Bastholt, L Wirth, LJ Martins, RG Locati, LD Jarzab, B Pacini, F Daumerie, C Droz, JP Eschenberg, MJ Sun, YN Juan, T Stepan, DE Sherman, SI AF Schlumberger, Martin J. Elisei, Rossella Bastholt, Lars Wirth, Lori J. Martins, Renato G. Locati, Laura D. Jarzab, Barbara Pacini, Furio Daumerie, Chantal Droz, Jean-Pierre Eschenberg, Michael J. Sun, Yu-Nien Juan, Todd Stepan, Daniel E. Sherman, Steven I. TI Phase II Study of Safety and Efficacy of Motesanib in Patients With Progressive or Symptomatic, Advanced or Metastatic Medullary Thyroid Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the European-Thyroid-Association CY SEP 01-05, 2007 CL Leipzig, GERMANY SP European Thyroid Assoc ID MULTIPLE ENDOCRINE NEOPLASIA; RET PROTOONCOGENE; MULTIKINASE INHIBITOR; SOLID TUMORS; CARCINOMA; HYPOTHYROIDISM; CALCITONIN; MUTATIONS; AMG-706; ANGIOGENESIS AB Purpose This phase II study investigated the efficacy and tolerability of motesanib, an investigational, highly selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit in advanced medullary thyroid cancer (MTC). Patients and Methods Patients with locally advanced or metastatic, progressive or symptomatic MTC received motesanib 125 mg/d orally for up to 48 weeks or until unacceptable toxicity or disease progression. The primary end point was objective response by independent review. Other end points included duration of response, progression-free survival, safety, pharmacokinetics, and changes in tumor markers. Results Of 91 enrolled patients who received motesanib, two (2%) achieved objective response (95% CI, 0.3% to 7.7%); their duration of response was 32 weeks (censored) and 21 weeks (disease progressed). Eighty-one percent of patients had stable disease (48% had durable stable disease >= 24 weeks), 8% had disease progression as best response, and 9% were not evaluated; 76% experienced a decrease from baseline in target lesion measurement. Median progression-free survival was 48 weeks (95% CI, 43 to 56 weeks). Among patients with tumor marker analysis, 69 (83%) of 83 and 63 (75%) of 84 had decreased serum calcitonin and carcinoembryonic antigen during treatment, respectively, compared with baseline. The most common treatment-related adverse events were diarrhea (41%), fatigue (41%), hypothyroidism (29%), hypertension (27%), and anorexia (27%). In pharmacokinetic analyses, motesanib trough concentrations were lower compared with differentiated thyroid cancer patients from the same study. Conclusion Although the objective response rate was low, a significant proportion of MTC patients (81%) achieved stable disease while receiving motesanib. C1 [Schlumberger, Martin J.] Univ Paris 11, Inst Gustave Roussy, F-94805 Villejuif, France. Ctr Leon Berard, F-69373 Lyon, France. Univ Pisa, Pisa, Italy. Ist Nazl Tumori, I-20133 Milan, Italy. Univ Siena, I-53100 Siena, Italy. Odense Univ Hosp, DK-5000 Odense, Denmark. Maria Sklodowska Curie Mem Canc Ctr, Gliwice, Poland. Inst Oncol, Gliwice, Poland. Catholic Univ Louvain, B-1200 Brussels, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, Seattle, WA 98195 USA. Amgen Inc, Thousand Oaks, CA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Schlumberger, MJ (reprint author), Univ Paris 11, Inst Gustave Roussy, Rue Camille Desmoulins, F-94805 Villejuif, France. EM martin.schlumberger@igr.fr RI Locati, Laura /B-8163-2017; OI Locati, Laura /0000-0003-3315-2580; Sherman, Steven/0000-0002-3079-5153 NR 32 TC 199 Z9 204 U1 1 U2 11 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2009 VL 27 IS 23 BP 3794 EP 3801 DI 10.1200/JCO.2008.18.7815 PG 8 WC Oncology SC Oncology GA 480XF UT WOS:000268769900012 PM 19564535 ER PT J AU Treon, SP Ioakimidis, L Soumerai, JD Patterson, CJ Sheehy, P Nelson, M Willen, M Matous, J Mattern, J Diener, JG Keogh, GP Myers, TJ Boral, A Birner, A Esseltine, DL Ghobrial, IM AF Treon, Steven P. Ioakimidis, Leukothea Soumerai, Jacob D. Patterson, Christopher J. Sheehy, Patricia Nelson, Marybeth Willen, Michael Matous, Jeffrey Mattern, John, II Diener, Jakow G. Keogh, George P. Myers, Thomas J. Boral, Andy Birner, Ann Esseltine, Dixie L. Ghobrial, Irene M. TI Primary Therapy of Waldenstrom Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MANTLE-CELL LYMPHOMA; PROTEASOME INHIBITOR BORTEZOMIB; CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; COOPERATIVE-ONCOLOGY-GROUP; RELAPSED MULTIPLE-MYELOMA; NON-HODGKINS-LYMPHOMA; PHASE-II; IN-VITRO; CHOP-R AB Purpose We examined the activity of bortezomib, dexamethasone, and rituximab (BDR) in patients with symptomatic, untreated Waldenstrom macroglobulinemia (WM). Patients and Methods A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy. Twenty-three patients received a median of seven cycles of treatment. Results Median bone marrow disease involvement declined from 55% to 10% (P = .0004), serum immunoglobulin M levels declined from 4,830 to 1,115 mg/dL (P = .0001), and hematocrit increased from 29.8% to 38.2% (P = .0002) at best response. The overall response rates and major response rates were 96% and 83% with three complete responses, two near complete responses, three very good partial responses, 11 partial responses, and three minor responses. Responses occurred at a median of 1.4 months. With a median follow-up of 22.8 months, 18 of 23 patients remained free of disease progression. Peripheral neuropathy was the most common toxicity, and it resolved to grade <= 1 in 13 of 16 patients at a median of 6.0 months. Four of the first seven treated patients developed herpes zoster, resulting in the institution of prophylactic antiviral therapy. Conclusion The results demonstrate that BDR produces rapid and durable responses, along with high rates of response and complete remissions in WM. Herpes zoster prophylaxis is necessary with BDR, and reversible peripheral neuropathy was the most common toxicity leading to premature discontinuation of bortezomib in 61% of patients. Exploration of alternative schedules for bortezomib administration that includes weekly dosing should be pursued. C1 [Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. New York Oncol & Hematol, Latham, NY USA. Rocky Mt Canc Ctr, Denver, CO USA. Virginia Oncol Associates, Newport News, VA USA. Littleton Reg Hosp, Littleton, NH USA. Charleston Hematol Oncol Associates, Charleston, SC USA. Takeda Oncol Co, Millennium, Cambridge, MA USA. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu FU Peter and Helen Bing Fund for Waldenstrom's Macroglobulinemia at the Dana-Farber Cancer Institute, Millennium; Takeda Oncology Company; National Institutes of Health [K23CA087977-03] FX Supported by the Peter and Helen Bing Fund for Waldenstrom's Macroglobulinemia at the Dana-Farber Cancer Institute, Millennium: The Takeda Oncology Company, and National Institutes of Health Career Development Award No. K23CA087977-03 (S. P. T.). NR 47 TC 91 Z9 95 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2009 VL 27 IS 23 BP 3830 EP 3835 DI 10.1200/JCO.2008.20.4677 PG 6 WC Oncology SC Oncology GA 480XF UT WOS:000268769900017 PM 19506160 ER PT J AU Meropol, NJ Schrag, D Smith, TJ Mulvey, TM Langdon, RM Blum, D Ubel, PA Schnipper, LE AF Meropol, Neal J. Schrag, Deborah Smith, Thomas J. Mulvey, Therese M. Langdon, Robert M., Jr. Blum, Diane Ubel, Peter A. Schnipper, Lowell E. TI American Society of Clinical Oncology Guidance Statement: The Cost of Cancer Care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MEDICAL-CARE; DRUG; FUTURE; INSURANCE; ADHERENCE AB Advances in early detection, prevention, and treatment have resulted in consistently falling cancer death rates in the United States. In parallel with these advances have come significant increases in the cost of cancer care. It is well established that the cost of health care (including cancer care) in the United States is growing more rapidly than the overall economy. In part, this is a result of the prices and rapid uptake of new agents and other technologies, including advances in imaging and therapeutic radiology. Conventional understanding suggests that high prices may reflect the costs and risks associated with the development, production, and marketing of new drugs and technologies, many of which are valued highly by physicians, patients, and payers. The increasing cost of cancer care impacts many stakeholders who play a role in a complex health care system. Our patients are the most vulnerable because they often experience uneven insurance coverage, leading to financial strain or even ruin. Other key groups include pharmaceutical manufacturers that pass along research, development, and marketing costs to the consumer; providers of cancer care who dispense increasingly expensive drugs and technologies; and the insurance industry, which ultimately passes costs to consumers. Increasingly, the economic burden of health care in general, and high-quality cancer care in particular, will be less and less affordable for an increasing number of Americans unless steps are taken to curb current trends. The American Society of Clinical Oncology (ASCO) is committed to improving cancer prevention, diagnosis, and treatment and eliminating disparities in cancer care through support of evidence-based and cost-effective practices. To address this goal, ASCO established a Cost of Care Task Force, which has developed this Guidance Statement on the Cost of Cancer Care. This Guidance Statement provides a concise overview of the economic issues facing stakeholders in the cancer community. It also recommends that the following steps be taken to address immediate needs: recognition that patient-physician discussions regarding the cost of care are an important component of high-quality care; the design of educational and support tools for oncology providers to promote effective communication about costs with patients; and the development of resources to help educate patients about the high cost of cancer care to help guide their decision making regarding treatment options. Looking to the future, this Guidance Statement also recommends that ASCO develop policy positions to address the underlying factors contributing to the increased cost of cancer care. Doing so will require a clear understanding of the factors that drive these costs, as well as potential modifications to the current cancer care system to ensure that all Americans have access to high-quality, cost-effective care. C1 [Schnipper, Lowell E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA USA. Dana Farber Canc Inst, Boston, MA USA. Commonwealth Hematol Oncol, Quincy, MA USA. Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. Oncol Hematol W PC, Omaha, NE USA. CancerCare, New York, NY USA. Univ Michigan, Ctr Behav & Decis Sci Med, Ann Arbor, MI 48109 USA. Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI USA. RP Schnipper, LE (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM lschnipp@bidmc.harvard.edu NR 43 TC 191 Z9 194 U1 3 U2 22 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2009 VL 27 IS 23 BP 3868 EP 3874 DI 10.1200/JCO.2009.23.1183 PG 7 WC Oncology SC Oncology GA 480XF UT WOS:000268769900023 PM 19581533 ER PT J AU Sheikh, SI Stemmer-Rachamimov, A Attar, EC AF Sheikh, Sarah I. Stemmer-Rachamimov, Anat Attar, Eyal C. TI Autopsy Diagnosis of Progressive Multifocal Leukoencephalopathy With JC Virus-Negative CSF After Cord Blood Stem-Cell Transplantation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DISEASE C1 [Sheikh, Sarah I.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. [Attar, Eyal C.] Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. RP Sheikh, SI (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 11 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2009 VL 27 IS 23 BP E46 EP E47 DI 10.1200/JCO.2009.22.4451 PG 2 WC Oncology SC Oncology GA 480XF UT WOS:000268769900024 PM 19451419 ER PT J AU Avila-Rios, S Ormsby, CE Carlson, JM Valenzuela-Ponce, H Blanco-Heredia, J Garrido-Rodriguez, D Garcia-Morales, C Heckerman, D Brumme, ZL Mallal, S John, M Espinosa, E Reyes-Teran, G AF Avila-Rios, Santiago Ormsby, Christopher E. Carlson, Jonathan M. Valenzuela-Ponce, Humberto Blanco-Heredia, Juan Garrido-Rodriguez, Daniela Garcia-Morales, Claudia Heckerman, David Brumme, Zabrina L. Mallal, Simon John, Mina Espinosa, Enrique Reyes-Teran, Gustavo TI Unique features of HLA-mediated HIV evolution in a Mexican cohort: a comparative study SO RETROVIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE ESCAPE; RESTRICTED IMMUNE-RESPONSES; CLASS-I; POPULATION-LEVEL; CELL RESPONSES; SELECTIVE PRESSURES; PRIMARY INFECTION; LATIN-AMERICA; VIRAL LOAD AB Background: Mounting evidence indicates that HLA-mediated HIV evolution follows highly stereotypic pathways that result in HLA-associated footprints in HIV at the population level. However, it is not known whether characteristic HLA frequency distributions in different populations have resulted in additional unique footprints. Methods: The phylogenetic dependency network model was applied to assess HLA-mediated evolution in datasets of HIV pol sequences from free plasma viruses and peripheral blood mononuclear cell (PBMC)-integrated proviruses in an immunogenetically unique cohort of Mexican individuals. Our data were compared with data from the IHAC cohort, a large multi-center cohort of individuals from Canada, Australia and the USA. Results: Forty three different HLA-HIV codon associations representing 30 HLA-HIV codon pairs were observed in the Mexican cohort (q < 0.2). Strikingly, 23 (53%) of these associations differed from those observed in the well-powered IHAC cohort, strongly suggesting the existence of unique characteristics in HLA-mediated HIV evolution in the Mexican cohort. Furthermore, 17 of the 23 novel associations involved HLA alleles whose frequencies were not significantly different from those in IHAC, suggesting that their detection was not due to increased statistical power but to differences in patterns of epitope targeting. Interestingly, the consensus differed in four positions between the two cohorts and three of these positions could be explained by HLA-associated selection. Additionally, different HLA-HIV codon associations were seen when comparing HLA-mediated selection in plasma viruses and PBMC archived proviruses at the population level, with a significantly lower number of associations in the proviral dataset. Conclusion: Our data support universal HLA-mediated HIV evolution at the population level, resulting in detectable HLA-associated footprints in the circulating virus. However, it also strongly suggests that unique genetic backgrounds in different HIV-infected populations may influence HIV evolution in a particular direction as particular HLA-HIV codon associations are determined by specific HLA frequency distributions. Our analysis also suggests a dynamic HLA-associated evolution in HIV with fewer HLA-HIV codon associations observed in the proviral compartment, which is likely enriched in early archived HIV sequences, compared to the plasma virus compartment. These results highlight the importance of comparative HIV evolutionary studies in immunologically different populations worldwide. C1 [Avila-Rios, Santiago; Ormsby, Christopher E.; Valenzuela-Ponce, Humberto; Blanco-Heredia, Juan; Garrido-Rodriguez, Daniela; Garcia-Morales, Claudia; Espinosa, Enrique; Reyes-Teran, Gustavo] Natl Inst Resp Dis, Ctr Res Infect Dis, Mexico City, DF, Mexico. [Avila-Rios, Santiago] Univ Nacl Autonoma Mexico, Fac Med, Mexico City 04510, DF, Mexico. [Carlson, Jonathan M.; Heckerman, David] Microsoft Res, ESci Grp, Redmond, WA USA. [Brumme, Zabrina L.] Massachusetts Gen Hosp, Massachusetts Inst Technol & Harvard, Ragon Inst, Boston, MA 02114 USA. [Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Mallal, Simon; John, Mina] Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. [Mallal, Simon; John, Mina] Murdoch Univ, Perth, WA, Australia. RP Avila-Rios, S (reprint author), Natl Inst Resp Dis, Ctr Res Infect Dis, Mexico City, DF, Mexico. EM santiago.avila@cieni.org.mx; christopher.ormsby@cieni.org.mx; carlson@microsoft.com; humberto.valenzuela@cieni.org.mx; juan.blanco@cieni.org.mx; daniela.garrido@cieni.org.mx; claudia.garcia@cieni.org.mx; heckerma@microsoft.com; zbrumme@partners.org; S.Mallal@murdoch.edu.au; M.John@iiid.com.au; enrique.espinosa@cieni.org.mx; reyesteran@cieni.org.mx OI Espinosa, Enrique/0000-0002-3231-1626; Blanco Heredia, Juan/0000-0001-9526-7450 FU CONACYT [U48159M]; Fundacion Mexico Vivo; Comision de Equidad y Genero de la H. Camara de Diputados; CONACyT; Canadian Institutes for Health Research (CIHR) FX Sponsorship: This work was supported by grants from CONACYT U48159M, Fundacion Mexico Vivo, and Comision de Equidad y Genero de la H. Camara de Diputados. SAR was supported by a scholarship from CONACyT. ZLB is supported by a post-doctoral fellowship from the Canadian Institutes for Health Research (CIHR). NR 57 TC 18 Z9 18 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 10 PY 2009 VL 6 AR 72 DI 10.1186/1742-4690-6-72 PG 23 WC Virology SC Virology GA 498MO UT WOS:000270145200001 PM 19664284 ER PT J AU Moreno, SG Sutton, AJ Turner, EH Abrams, KR Cooper, NJ Palmer, TM Ades, AE AF Moreno, Santiago G. Sutton, Alex J. Turner, Erick H. Abrams, Keith R. Cooper, Nicola J. Palmer, Tom M. Ades, A. E. TI Novel methods to deal with publication biases: secondary analysis of antidepressant trials in the FDA trial registry database and related journal publications SO BRITISH MEDICAL JOURNAL LA English DT Article ID OUTCOME REPORTING BIAS; INTENTION-TO-TREAT; RANDOMIZED CONTROLLED-TRIALS; MISLEADING FUNNEL PLOT; EMPIRICAL-EVIDENCE; CLINICAL-TRIALS; EFFECT SIZE; FILL METHOD; METAANALYSIS; HETEROGENEITY AB Objective To assess the performance of novel contour enhanced funnel plots and a regression based adjustment method to detect and adjust for publication biases. Design Secondary analysis of a published systematic literature review. Data sources Placebo controlled trials of antidepressants previously submitted to the US Food and Drug Administration (FDA) and matching journal publications. Methods Publication biases were identified using novel contour enhanced funnel plots, a regression based adjustment method, Egger's test, and the trim and fill method. Results were compared with a meta-analysis of the gold standard data submitted to the FDA. Results Severe asymmetry was observed in the contour enhanced funnel plot that appeared to be heavily influenced by the statistical significance of results, suggesting publication biases as the cause of the asymmetry. Applying the regression based adjustment method to the journal data produced a similar pooled effect to that observed by a meta-analysis of the FDA data. Contrasting journal and FDA results suggested that, in addition to other deviations from study protocol, switching from an intention to treat analysis to a per protocol one would contribute to the observed discrepancies between the journal and FDA results. Conclusion Novel contour enhanced funnel plots and a regression based adjustment method worked convincingly and might have an important part to play in combating publication biases. C1 [Moreno, Santiago G.; Sutton, Alex J.; Abrams, Keith R.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England. [Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. [Palmer, Tom M.] Univ Bristol, MRC Ctr Causal Anal Translat Epidemiol, Dept Social Med, Bristol BS8 1TH, Avon, England. [Ades, A. E.] Univ Bristol, Dept Community Based Med, Bristol BS8 1TH, Avon, England. RP Moreno, SG (reprint author), Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England. EM sgm8@le.ac.uk OI Turner, Erick/0000-0002-3522-3357; Abrams, Keith/0000-0002-7557-1567 FU Medical Research Council Health Services Research Collaboration FX SGM was supported by a Medical Research Council Health Services Research Collaboration studentship in the UK. AEA was funded by the Medical Research Council Health Services Research Collaboration. The funding agreement ensured the authors' independence in designing the study, interpreting the data, and writing and publishing the report. The corresponding author as well as the other authors had access to all the data and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 70 TC 71 Z9 71 U1 1 U2 10 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD AUG 7 PY 2009 VL 339 AR b2981 DI 10.1136/bmj.b2981 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 481KF UT WOS:000268808200002 PM 19666685 ER PT J AU Liu, ZY Habener, JF AF Liu, Zhengyu Habener, Joel F. TI Alpha Cells Beget Beta Cells SO CELL LA English DT Editorial Material ID PANCREAS; DIFFERENTIATION; GENE; MICE AB Understanding the origins of insulin-producing beta cells of the pancreas could lead to new treatments for diabetes. Collombat et al. ( 2009) now show that in response to injury, a population of pancreatic progenitor cells can give rise to glucagon-expressing alpha cells that then transdifferentiate into beta cells. C1 [Liu, Zhengyu; Habener, Joel F.] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Liu, ZY (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. EM zliu4@partners.org; jhabener@partners.org NR 9 TC 13 Z9 15 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD AUG 7 PY 2009 VL 138 IS 3 BP 424 EP 426 DI 10.1016/j.cell.2009.07.022 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 480XZ UT WOS:000268771900005 PM 19665963 ER PT J AU Brack, A AF Brack, Andrew TI Adult Muscle Stem Cells Avoid Death and Paxes SO CELL STEM CELL LA English DT Editorial Material ID MYOGENIC SATELLITE CELLS; PROGENITOR CELLS; SPECIFICATION; POPULATION; RENEWAL AB In a recent Nature publication, Lepper et al. (2009) use cell-specific lineage tracing and temporally controllable gene deletion approaches to study muscle stem cell function and reveal age-dependent requirements for Pax gene expression. C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Brack, A (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St,MGH Charles River Plaza N,Room 4, Boston, MA 02114 USA. EM brack.andrew@mgh.harvard.edu NR 10 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD AUG 7 PY 2009 VL 5 IS 2 BP 132 EP 134 DI 10.1016/j.stem.2009.07.005 PG 3 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 490PB UT WOS:000269511900005 PM 19664985 ER PT J AU Dietz, H Douglas, SM Shih, WM AF Dietz, Hendrik Douglas, Shawn M. Shih, William M. TI Folding DNA into Twisted and Curved Nanoscale Shapes SO SCIENCE LA English DT Article ID DOUBLE-CROSSOVER MOLECULES; CONDUCTIVE NANOWIRES; NANOTUBES; NANOSTRUCTURES; OCTAHEDRON; DESIGN AB We demonstrate the ability to engineer complex shapes that twist and curve at the nanoscale from DNA. Through programmable self-assembly, strands of DNA are directed to form a custom-shaped bundle of tightly cross-linked double helices, arrayed in parallel to their helical axes. Targeted insertions and deletions of base pairs cause the DNA bundles to develop twist of either handedness or to curve. The degree of curvature could be quantitatively controlled, and a radius of curvature as tight as 6 nanometers was achieved. We also combined multiple curved elements to build several different types of intricate nanostructures, such as a wireframe beach ball or square-toothed gears. C1 [Dietz, Hendrik; Douglas, Shawn M.; Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Dietz, Hendrik; Douglas, Shawn M.; Shih, William M.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA. [Douglas, Shawn M.; Shih, William M.] Harvard Univ, Wyss Inst Biologically Inspired Engn, Cambridge, MA 02138 USA. RP Shih, WM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM william_shih@dfci.harvard.edu OI Douglas, Shawn/0000-0001-5398-9041 FU Claudia Adams Barr Program; Wyss Institute for Biologically Inspired Engineering; NIH [1DP2OD004641-01]; Feodor-Lynen Humboldt FX This work was supported by Claudia Adams Barr Program Investigator, Wyss Institute for Biologically Inspired Engineering, and NIH New Innovator (1DP2OD004641-01) grants to W.M.S. and a Feodor-Lynen Humboldt Fellowship to H.D. H.D., S.M.D., and W.M.S. designed the research for this paper. H.D. developed rules for twisting and bending; H.D. and S.M.D. designed all shapes; H.D. and S.M.D. collected data; H.D. analyzed data; S.M.D. provided caDNAno software support; and H.D., W.M.S., and S.M.D. wrote the manuscript. NR 27 TC 460 Z9 469 U1 19 U2 187 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD AUG 7 PY 2009 VL 325 IS 5941 BP 725 EP 730 DI 10.1126/science.1174251 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 480HF UT WOS:000268723700043 PM 19661424 ER PT J AU Frank, DA AF Frank, David A. TI STAT6 in PMBL: pathogenic or passenger? SO BLOOD LA English DT Editorial Material ID B-CELL LYMPHOMA; HODGKIN LYMPHOMA; ACTIVATION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 6 PY 2009 VL 114 IS 6 BP 1133 EP 1134 DI 10.1182/blood-2009-05-221770 PG 2 WC Hematology SC Hematology GA 480XI UT WOS:000268770200001 PM 19661272 ER PT J AU Lane, SW Scadden, DT Gilliland, DG AF Lane, Steven W. Scadden, David T. Gilliland, D. Gary TI The leukemic stem cell niche: current concepts and therapeutic opportunities SO BLOOD LA English DT Review ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC PROGENITOR CELLS; ACUTE MYELOGENOUS LEUKEMIA; BONE-MARROW MICROENVIRONMENT; ACUTE LYMPHOBLASTIC-LEUKEMIA; BCR-ABL; IN-VIVO; OSTEOBLASTIC NICHE; ENDOTHELIAL-CELLS; MULTIPLE-MYELOMA AB The genetic events that contribute to the pathogenesis of acute myeloid leukemia are among the best characterized of all human malignancies. However, with notable exceptions such as acute promyelocytic leukemia, significant improvements in outcome based on these insights have not been forthcoming. Acute myeloid leukemia is a paradigm of cancer stem (or leukemia initiating) cells with hierarchy analogous to that seen in hematopoiesis. Normal hematopoiesis requires complex bidirectional interactions between the bone marrow microenvironment (or niche) and hematopoietic stem cells (HSCs). These interactions are critical for the maintenance of normal HSC quiescence and perturbations can influence HSC self-renewal. Leukemia stem cells (LSCs), which also possess limitless self-renewal, may hijack these homeostatic mechanisms, take refuge within the sanctuary of the niche during chemotherapy, and consequently contribute to eventual disease relapse. We will discuss the emerging evidence supporting the importance of the bone marrow microenvironment in LSC survival and consider the physiologic interactions of HSCs and the niche that inform our understanding of microenvironment support of LSCs. Finally, we will discuss approaches for the rational development of therapies that target the microenvironment. (Blood. 2009; 114: 1150-1157) C1 [Lane, Steven W.; Gilliland, D. Gary] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Lane, Steven W.] Univ Queensland, Brisbane, Qld, Australia. [Scadden, David T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Scadden, David T.; Gilliland, D. Gary] Harvard Stem Cell Inst, Boston, MA USA. [Scadden, David T.; Gilliland, D. Gary] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA. [Gilliland, D. Gary] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Lane, SW (reprint author), Brigham & Womens Hosp, Div Hematol, Karp Family Res Bldg,5th Floor,1 Blackfan Cir, Boston, MA 02115 USA. EM swlane@partners.org RI Lane, Steven/C-3215-2012 OI Lane, Steven/0000-0002-8050-6209 FU US National Institutes of Health (NIH; Bethesda, MD); Howard Hughes Medical Institute (Boston, MA); Leukemia & Lymphoma Society (White Plains, NY); Doris Duke Charitable Foundation (New York, NY); Myeloproliferative Disorders Foundation (Chicago, IL); NIH (National Heart, Lung and Blood Institute; National Cancer Institute; and the National Institute of Diabetes and Digestive and Kidney Diseases); Ellison Medical Foundation; Harvard Stem Cell Institute; Haematology Society of Australia and New Zealand; Royal Brisbane and Women's Hospital Foundation; Australia/US Fulbright Commission FX We acknowledge the insightful comments and critical review of the manuscript provided by Drs S. Frohling and S. Sykes.; D. G. G. received funding support from the US National Institutes of Health (NIH; Bethesda, MD), the Howard Hughes Medical Institute (Boston, MA), the Leukemia & Lymphoma Society (White Plains, NY), the Doris Duke Charitable Foundation (New York, NY), and the Myeloproliferative Disorders Foundation (Chicago, IL). D. T. S. received funding from NIH (National Heart, Lung and Blood Institute; National Cancer Institute; and the National Institute of Diabetes and Digestive and Kidney Diseases), the Ellison Medical Foundation, and the Harvard Stem Cell Institute. S. W. L. has received funding support from the Haematology Society of Australia and New Zealand, Royal Brisbane and Women's Hospital Foundation, and the Australia/US Fulbright Commission. NR 91 TC 225 Z9 241 U1 2 U2 32 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 6 PY 2009 VL 114 IS 6 BP 1150 EP 1157 DI 10.1182/blood-2009-01-202606 PG 8 WC Hematology SC Hematology GA 480XI UT WOS:000268770200008 PM 19401558 ER PT J AU Zhu, PC Martinvalet, D Chowdhury, D Zhang, D Schlesinger, A Lieberman, J AF Zhu, Pengcheng Martinvalet, Denis Chowdhury, Dipanjan Zhang, Dong Schlesinger, Ann Lieberman, Judy TI The cytotoxic T lymphocyte protease granzyme A cleaves and inactivates poly(adenosine 5 '-diphosphate-ribose) polymerase-1 SO BLOOD LA English DT Article ID DOUBLE-STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE; CELL-DEATH; MEDIATED APOPTOSIS; DNA-DAMAGE; PARP-1; REPAIR; COMPLEX; ACTIVATION; PROTEINS AB Granzyme A(GzmA) in killer cells induces caspase-independent programmed cell death. In this study, we show that GzmA cleaves the DNA damage sensor poly( adenosine 5'-diphosphate-ribose) polymerase-1 (PARP-1) after Lys(498) in its automodification domain, separating the DNA binding domain from the catalytic domain, which interferes with repair of GzmA-induced DNA damage and enhances susceptibility to GzmA-mediated death. Overexpressing K498A PARP-1 reduces GzmA-mediated death and drives dying cells to necrosis rather than apoptosis. Conversely, inhibiting or genetically disrupting PARP-1 enhances cell vulnerability. The N-terminal GzmA cleavage fragment of PARP-1 acts as a PARP-1 dominant negative, binding to DNA and blocking DNA repair. Disrupting PARP-1, which is also a caspase target, is therefore required for efficient apoptosis by both caspase-independent and caspase-dependent pathways. (Blood. 2009; 114: 1205-1216) C1 [Zhu, Pengcheng; Martinvalet, Denis; Chowdhury, Dipanjan; Zhang, Dong; Schlesinger, Ann; Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Zhu, Pengcheng; Martinvalet, Denis; Chowdhury, Dipanjan; Zhang, Dong; Schlesinger, Ann; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015 FU National Institutes of Health [AI-45587]; Leukemia & Lymphoma Society fellowship FX This work was supported by National Institutes of Health grant AI-45587 (to J.L.) and a Leukemia & Lymphoma Society fellowship (to D. C.). NR 48 TC 27 Z9 30 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 6 PY 2009 VL 114 IS 6 BP 1205 EP 1216 DI 10.1182/blood-2008-12-195768 PG 12 WC Hematology SC Hematology GA 480XI UT WOS:000268770200014 PM 19506301 ER PT J AU Nilsson, R Schultz, IJ Pierce, EL Soltis, KA Naranuntarat, A Ward, DM Baughman, JM Paradkar, PN Kingsley, PD Culotta, VC Kaplan, J Palis, J Paw, BH Mootha, VK AF Nilsson, Roland Schultz, Iman J. Pierce, Eric L. Soltis, Kathleen A. Naranuntarat, Amornrat Ward, Diane M. Baughman, Joshua M. Paradkar, Prasad N. Kingsley, Paul D. Culotta, Valeria C. Kaplan, Jerry Palis, James Paw, Barry H. Mootha, Vamsi K. TI Discovery of Genes Essential for Heme Biosynthesis through Large-Scale Gene Expression Analysis SO CELL METABOLISM LA English DT Article ID LINKED SIDEROBLASTIC ANEMIA; MITOCHONDRIAL CARRIER FAMILY; IRON HOMEOSTASIS; ERYTHROID-DIFFERENTIATION; REGULATORY NETWORK; MICROCYTIC ANEMIA; TRANSPORTER GENE; CELLS; ZEBRAFISH; DEFICIENCY AB Heme biosynthesis consists of a series of eight enzymatic reactions that originate in mitochondria and continue in the cytosol before returning to mitochondria. Although these core enzymes are well studied, additional mitochondrial transporters and regulatory factors are predicted to be required. To discover such unknown components, we utilized a large-scale computational screen to identify mitochondrial proteins whose transcripts consistently coexpress with the core machinery of heme biosynthesis. We identified SLC25A39, SLC22A4, and TMEM14C, which are putative mitochondrial transporters, as well as C1orf69 and ISCA1, which are iron-sulfur cluster proteins. Targeted knockdowns of all five genes in zebrafish resulted in profound anemia without impacting erythroid lineage specification. Moreover, silencing of Slc25a39 in murine erythroleukemia cells impaired iron incorporation into protoporphyrin IX, and vertebrate Slc25a39 complemented an iron homeostasis defect in the orthologous yeast mtm1 Delta deletion mutant. Our results advance the molecular understanding of heme biosynthesis and offer promising candidate genes for inherited anemias. C1 [Schultz, Iman J.; Pierce, Eric L.; Soltis, Kathleen A.; Paw, Barry H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol,Dept Med, Boston, MA 02115 USA. [Nilsson, Roland; Baughman, Joshua M.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Nilsson, Roland; Baughman, Joshua M.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02115 USA. [Schultz, Iman J.; Pierce, Eric L.; Soltis, Kathleen A.; Paw, Barry H.] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Nilsson, Roland; Baughman, Joshua M.; Mootha, Vamsi K.] Harvard Univ, MIT, Broad Inst, Cambridge, MA 02142 USA. [Naranuntarat, Amornrat; Culotta, Valeria C.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Div Toxicol, Baltimore, MD 21205 USA. [Ward, Diane M.; Paradkar, Prasad N.; Kaplan, Jerry] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA. [Kingsley, Paul D.; Palis, James] Univ Rochester, Sch Med & Dent, Dept Pediat, Ctr Pediat Biomed Res, Rochester, NY 14642 USA. RP Paw, BH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol,Dept Med, Boston, MA 02115 USA. EM bpaw@rics.bwh.harvard.edu; vamsi@hms.harvard.edu FU Knut and Alice Wallenberg Foundation; Netherlands Organisation for Scientific Research/NWO; March of Dimes Foundation; American Diabetes Association/Smith Family Foundation; Howard Hughes Medical Institute; JHU NIEHS center; American Society of Hematology; NIH [R01ES08996, R01DK052380, R01DK070838, P01HL032262, R01GM077465] FX We thank Christian Lawrence, Jason Best, and others for the zebrafish animal husbandry; Babette Gwynn and Luanne Peters for providing mouse fetal liver RNA and adult bone marrow cells; and Joe Italiano for access to the CCD camera and MetaMorph software. We thank members of our labs for critical reading of this manuscript. This work was supported, in part, by the Knut and Alice Wallenberg Foundation (R.N.); the Netherlands Organisation for Scientific Research/NWO (I.J.S.); the March of Dimes Foundation (B.H.P.); the American Diabetes Association/Smith Family Foundation (V.K.M.); the Howard Hughes Medical Institute (V.K.M.); the JHU NIEHS center (V.C.C.); the American Society of Hematology (K.A.S.); and the NIH (P.D.K.; V.C.C., R01ES08996; J.K., R01DK052380; J.P.; B.H.P., R01DK070838 and P01HL032262; V.K.M., R01GM077465). NR 60 TC 89 Z9 96 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD AUG 6 PY 2009 VL 10 IS 2 BP 119 EP 130 DI 10.1016/j.cmet.2009.06.012 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 480DB UT WOS:000268711200009 PM 19656490 ER PT J AU Purcell, SM Wray, NR Stone, JL Visscher, PM O'Donovan, MC Sullivan, PF Sklar, P Ruderfer, DM McQuillin, A Morris, DW O'Dushlaine, CT Corvin, A Holmans, PA Macgregor, S Gurling, H Blackwood, DHR Craddock, NJ Gill, M Hultman, CM Kirov, GK Lichtenstein, P Muir, WJ Owen, MJ Pato, CN Scolnick, EM St Clair, D Williams, NM Georgieva, L Nikolov, I Norton, N Williams, H Toncheva, D Milanova, V Thelander, EF Sullivan, P Kenny, E Quinn, EM Choudhury, K Datta, S Pimm, J Thirumalai, S Puri, V Krasucki, R Lawrence, J Quested, D Bass, N Crombie, C Fraser, G Kuan, SL Walker, N McGhee, KA Pickard, B Malloy, P Maclean, AW Van Beck, M Pato, MT Medeiros, H Middleton, F Carvalho, C Morley, C Fanous, A Conti, D Knowles, JA Ferreira, CP Macedo, A Azevedo, MH Kirby, AN Ferreira, MAR Daly, MJ Chambert, K Kuruvilla, F Gabriel, SB Ardlie, K Moran, JL AF Purcell, Shaun M. Wray, Naomi R. Stone, Jennifer L. Visscher, Peter M. O'Donovan, Michael C. Sullivan, Patrick F. Sklar, Pamela Ruderfer, Douglas M. McQuillin, Andrew Morris, Derek W. O'Dushlaine, Colm T. Corvin, Aiden Holmans, Peter A. Macgregor, Stuart Gurling, Hugh Blackwood, Douglas H. R. Craddock, Nick J. Gill, Michael Hultman, Christina M. Kirov, George K. Lichtenstein, Paul Muir, Walter J. Owen, Michael J. Pato, Carlos N. Scolnick, Edward M. St Clair, David Williams, Nigel M. Georgieva, Lyudmila Nikolov, Ivan Norton, N. Williams, H. Toncheva, Draga Milanova, Vihra Thelander, Emma F. Sullivan, Patrick Kenny, Elaine Quinn, Emma M. Choudhury, Khalid Datta, Susmita Pimm, Jonathan Thirumalai, Srinivasa Puri, Vinay Krasucki, Robert Lawrence, Jacob Quested, Digby Bass, Nicholas Crombie, Caroline Fraser, Gillian Kuan, Soh Leh Walker, Nicholas McGhee, Kevin A. Pickard, Ben Malloy, Pat Maclean, Alan W. Van Beck, Margaret Pato, Michele T. Medeiros, Helena Middleton, Frank Carvalho, Celia Morley, Christopher Fanous, Ayman Conti, David Knowles, James A. Ferreira, Carlos Paz Macedo, Antonio Azevedo, M. Helena Kirby, Andrew N. Ferreira, Manuel A. R. Daly, Mark J. Chambert, Kimberly Kuruvilla, Finny Gabriel, Stacey B. Ardlie, Kristin Moran, Jennifer L. TI Common polygenic variation contributes to risk of schizophrenia and bipolar disorder SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; MULTIPLE RARE ALLELES; PSYCHIATRIC-DISORDERS; DISEASE; GENES; LOCI; TWIN AB Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%(1,2). We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases. C1 [Purcell, Shaun M.; Stone, Jennifer L.; Sklar, Pamela; Ruderfer, Douglas M.; Ferreira, Manuel A. R.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Purcell, Shaun M.; Stone, Jennifer L.; Sklar, Pamela; Ruderfer, Douglas M.; Scolnick, Edward M.; Kirby, Andrew N.; Ferreira, Manuel A. R.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Purcell, Shaun M.; Stone, Jennifer L.; Sklar, Pamela; Ruderfer, Douglas M.; Scolnick, Edward M.; Kirby, Andrew N.; Ferreira, Manuel A. R.; Daly, Mark J.; Chambert, Kimberly] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Purcell, Shaun M.; Stone, Jennifer L.; Sklar, Pamela; Ruderfer, Douglas M.; Kirby, Andrew N.; Ferreira, Manuel A. R.; Daly, Mark J.; Chambert, Kimberly; Kuruvilla, Finny; Gabriel, Stacey B.; Ardlie, Kristin; Moran, Jennifer L.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Wray, Naomi R.; Visscher, Peter M.; Macgregor, Stuart] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [O'Donovan, Michael C.; Holmans, Peter A.; Craddock, Nick J.; Kirov, George K.; Owen, Michael J.; Williams, Nigel M.; Georgieva, Lyudmila; Nikolov, Ivan; Norton, N.; Williams, H.] Cardiff Univ, Sch Med, Dept Psychol Med, MRC Ctr Neuropsychiat Genet & Gen, Cardiff C14 4XN, Wales. [Sullivan, Patrick F.; Sullivan, Patrick] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Sullivan, Patrick F.; Sullivan, Patrick] Univ N Carolina, Dept Psychiat & Epidemiol, Chapel Hill, NC 27599 USA. [McQuillin, Andrew; Gurling, Hugh; Choudhury, Khalid; Datta, Susmita; Pimm, Jonathan; Puri, Vinay; Krasucki, Robert; Lawrence, Jacob; Bass, Nicholas] UCL, Sch Med, Mol Psychiat Lab, Res Dept Mental Hlth Sci,Windeyer Inst Med Sci, London W1T 4JF, England. [Morris, Derek W.; O'Dushlaine, Colm T.; Corvin, Aiden; Gill, Michael; Kenny, Elaine; Quinn, Emma M.] Univ Dublin Trinity Coll, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 2, Ireland. [Morris, Derek W.; O'Dushlaine, Colm T.; Corvin, Aiden; Gill, Michael; Kenny, Elaine; Quinn, Emma M.] Univ Dublin Trinity Coll, Inst Mol Med, Dublin 2, Ireland. [Blackwood, Douglas H. R.; Muir, Walter J.; McGhee, Kevin A.; Pickard, Ben; Malloy, Pat; Maclean, Alan W.; Van Beck, Margaret] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland. [Hultman, Christina M.; Lichtenstein, Paul; Thelander, Emma F.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Hultman, Christina M.] Uppsala Univ, Dept Neurosci, SE-75017 Uppsala, Sweden. [Pato, Carlos N.; Pato, Michele T.; Medeiros, Helena; Carvalho, Celia; Fanous, Ayman; Conti, David; Knowles, James A.] Univ So Calif, Ctr Genom Psychiat, Los Angeles, CA 90033 USA. [St Clair, David; Walker, Nicholas] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland. [Crombie, Caroline; Fraser, Gillian] Univ Aberdeen, Dept Mental Hlth, Aberdeen AB25 2ZD, Scotland. [Toncheva, Draga] Univ Hosp Maichin Dom, Dept Med Genet, Sofia 1431, Bulgaria. [Milanova, Vihra] Alexander Univ Hosp, Psychiat Clin 1, Dept Psychiat, Sofia 1431, Bulgaria. [Thirumalai, Srinivasa] W Berkshire NHS Trust, Reading RG3 5LR, Berks, England. [Quested, Digby] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. [Kuan, Soh Leh] Ravenscraig Hosp, Greenock PA16 9HA, Scotland. [Middleton, Frank; Morley, Christopher] SUNY Syracuse, Upstate Med Univ Syracuse, Syracuse, NY 13210 USA. [Fanous, Ayman] Washington VA Med Ctr, Washington, DC 20422 USA. [Fanous, Ayman] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC 20057 USA. [Fanous, Ayman] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA. [Ferreira, Carlos Paz] Dept Psychiat, P-9500310 Sao Miguel, Azores, Portugal. [Macedo, Antonio; Azevedo, M. Helena] Univ Coimbra, Dept Psychiat, P-3004504 Coimbra, Portugal. RP Sklar, P (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, 185 Cambridge St, Boston, MA 02114 USA. EM shaun@pngu.mgh.harvard.edu; sklar@chgr.mgh.harvard.edu RI Morley, Christopher P/K-1907-2014; turton, miranda/F-4682-2011; Ferreira, Manuel/D-3609-2013; Gurling, Hugh/A-5029-2010; macedo santos, antonio/M-5737-2013; Pickard, Benjamin/K-3923-2014; Wray, Naomi/C-8639-2015; Holmans, Peter/F-4518-2015; Ruderfer, Douglas/M-5795-2016; McQuillin, Andrew/C-1623-2008; Macgregor, Stuart/C-6442-2009 OI Visscher, Peter/0000-0002-2143-8760; Corvin, Aiden/0000-0001-6717-4089; O'Donovan, Michael/0000-0001-7073-2379; Morris, Derek/0000-0002-3413-570X; Morley, Christopher P/0000-0003-0185-7148; Gill, Michael/0000-0003-0206-5337; lichtenstein, paul/0000-0003-3037-5287; de Oliveira Barreto Coimbra Carvalho, Celia Maria/0000-0003-4453-8139; Moran, Jennifer/0000-0002-5664-4716; macedo santos, antonio/0000-0003-2180-2718; Pickard, Benjamin/0000-0002-2374-6329; Wray, Naomi/0000-0001-7421-3357; Holmans, Peter/0000-0003-0870-9412; Ruderfer, Douglas/0000-0002-2365-386X; McQuillin, Andrew/0000-0003-1567-2240; Macgregor, Stuart/0000-0001-6731-8142 FU Stanley Medical Research Institute; Sylvan C. Herman Foundation [MH071681]; Medical Research Council (UK) Programme; National Institutes of Mental Health (USA) [CONTE: 2 P50 MH066392-05A1]; Swedish Council for Working Life and Social Research [FO 184/2000, 2001-2368]; Stanley Medical Research Institute [MH071681, MH077139]; Narsad Young Investigator Award; Australian National Health and Medical Research Council [389892, 442915, 496688, 496674]; Science Foundation Ireland; Health Research Board (Ireland); Wellcome Trust; National Institutes of Mental Health and the Department of Veterans Affairs FX We thank the patients and families who contributed to these studies. We also thank E. Lander, N. Patterson and members of the Medical and Population Genetics group at the Broad Institute of Harvard and Massachusetts Institute of Technology for valuable discussion, and members of the Broad Biological Samples and Genetic Analysis Platforms for sample management and genotyping. Weparticularly thank D. Levinson and P. Gejman for allowing access to the MGS samples, and J. Shi for analytic support with the MGS samples. The group at the Stanley Center for Psychiatric Research at the Broad Institute was supported by the Stanley Medical Research Institute (E. M. S.), the Sylvan C. Herman Foundation (E. M. S.), and MH071681 (P. S.). The Cardiff University group was supported by a Medical Research Council (UK) Programme grant and the National Institutes of Mental Health (USA) (CONTE: 2 P50 MH066392-05A1). The group at the Karolinska Institutet was supported by the Swedish Council for Working Life and Social Research (FO 184/2000; 2001-2368). The Massachusetts General Hospital group was supported by the Stanley Medical Research Institute (P. S.), MH071681 and MH077139 (P. S.) and a Narsad Young Investigator Award (S. M. P.). The group at the Queensland Institute of Medical Research was supported by the Australian National Health and Medical Research Council (grants 389892, 442915, 496688 and 496674) and thanks S. Gordon for data preparation. The Trinity College Dublin group was supported by Science Foundation Ireland, the Health Research Board (Ireland), the Stanley Medical Research Institute and the Wellcome Trust; Irish controls were supplied by J. McPartlin from the Trinity College Biobank. The work at the University of Aberdeen was partly funded by GlaxoSmithKline and Generation Scotland, Genetics Health Initiative. University College London clinical and control samples were collected with support from the Neuroscience Research Charitable Trust, the Camden and Islington Mental Health and Social Care Trust, East London and City Mental Heath Trust, the West Berkshire NHS Trust, the West London Mental Health Trust, Oxfordshire and Buckinghamshire Mental Health Partnership NHS Trust, South Essex Partnership NHS Foundation Trust, Gloucestershire Partnership NHS Foundation Trust, Mersey Care NHS Trust, Hampshire Partnership NHS Trust and the North East London Mental Health Trust. The collection of the University of Edinburgh cohort was supported by the Wellcome Trust Clinical Research Facility (Edinburgh) and grants from The Wellcome Trust, London and the Chief Scientist Office of the Scottish Government. The group at the University of North Carolina, Chapel Hill, was supported by MH074027, MH077139 and MH080403, the Sylvan C. Herman Foundation (P. F. S.) and the Stanley Medical Research Institute (P. F. S.). The group at the University of Southern California thanks the patients and their families for their collaboration, and acknowledges the support of the National Institutes of Mental Health and the Department of Veterans Affairs. NR 26 TC 1468 Z9 1501 U1 32 U2 286 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD AUG 6 PY 2009 VL 460 IS 7256 BP 748 EP 752 DI 10.1038/nature08185 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 479OO UT WOS:000268670300041 ER PT J AU Margaretten, ME Tierney, LM Dhaliwal, G AF Margaretten, Mary E. Tierney, Lawrence M., Jr. Dhaliwal, Gurpreet TI A Hard Diagnosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SCLERODERMA RENAL CRISIS; SCLEROSIS SINE SCLERODERMA; SYSTEMIC-SCLEROSIS C1 [Margaretten, Mary E.] Univ Calif San Francisco, Div Rheumatol, San Francisco, CA 94118 USA. [Tierney, Lawrence M., Jr.; Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA 94118 USA. [Tierney, Lawrence M., Jr.; Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. RP Margaretten, ME (reprint author), Univ Calif San Francisco, Div Rheumatol, 3333 Calif St,Suite 270, San Francisco, CA 94118 USA. EM mary.margaretten@ucsf.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 6 PY 2009 VL 361 IS 6 BP 613 EP 617 DI 10.1056/NEJMcps0804137 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 479NR UT WOS:000268667300013 PM 19657126 ER PT J AU Ramachandran, D Luo, CA Ma, TS Clark, JW AF Ramachandran, Deepa Luo, Chuan Ma, Tony S. Clark, John W., Jr. TI Using a human cardiovascular-respiratory model to characterize cardiac tamponade and pulsus paradoxus SO THEORETICAL BIOLOGY AND MEDICAL MODELLING LA English DT Article ID PERICARDIAL CONSTRAINT; STROKE VOLUME; GAS-EXCHANGE; BLOOD-FLOW; PRESSURE; INTERDEPENDENCE; DYNAMICS; EFFUSION; COLLAPSE; STATE AB Background: Cardiac tamponade is a condition whereby fluid accumulation in the pericardial sac surrounding the heart causes elevation and equilibration of pericardial and cardiac chamber pressures, reduced cardiac output, changes in hemodynamics, partial chamber collapse, pulsus paradoxus, and arterio-venous acid-base disparity. Our large-scale model of the human cardiovascular-respiratory system (H-CRS) is employed to study mechanisms underlying cardiac tamponade and pulsus paradoxus. The model integrates hemodynamics, whole-body gas exchange, and autonomic nervous system control to simulate pressure, volume, and blood flow. Methods: We integrate a new pericardial model into our previously developed H-CRS model based on a fit to patient pressure data. Virtual experiments are designed to simulate pericardial effusion and study mechanisms of pulsus paradoxus, focusing particularly on the role of the interventricular septum. Model differential equations programmed in C are solved using a 5(th)-order Runge-Kutta numerical integration scheme. MATLAB is employed for waveform analysis. Results: The H-CRS model simulates hemodynamic and respiratory changes associated with tamponade clinically. Our model predicts effects of effusion-generated pericardial constraint on chamber and septal mechanics, such as altered right atrial filling, delayed leftward septal motion, and prolonged left ventricular pre-ejection period, causing atrioventricular interaction and ventricular desynchronization. We demonstrate pericardial constraint to markedly accentuate normal ventricular interactions associated with respiratory effort, which we show to be the distinct mechanisms of pulsus paradoxus, namely, series and parallel ventricular interaction. Series ventricular interaction represents respiratory variation in right ventricular stroke volume carried over to the left ventricle via the pulmonary vasculature, whereas parallel interaction (via the septum and pericardium) is a result of competition for fixed filling space. We find that simulating active septal contraction is important in modeling ventricular interaction. The model predicts increased arterio-venous CO(2) due to hypoperfusion, and we explore implications of respiratory pattern in tamponade. Conclusion: Our modeling study of cardiac tamponade dissects the roles played by septal motion, atrioventricular and right-left ventricular interactions, pulmonary blood pooling, and the depth of respiration. The study fully describes the physiological basis of pulsus paradoxus. Our detailed analysis provides biophysically-based insights helpful for future experimental and clinical study of cardiac tamponade and related pericardial diseases. C1 [Ramachandran, Deepa; Luo, Chuan; Clark, John W., Jr.] Rice Univ, Dept Elect & Comp Engn, Houston, TX 77005 USA. [Ma, Tony S.] VA Med Ctr, Div Cardiol, Houston, TX 77030 USA. [Ma, Tony S.] Baylor Coll Med, Houston, TX 77030 USA. RP Clark, JW (reprint author), Rice Univ, Dept Elect & Comp Engn, Houston, TX 77005 USA. EM dpr2@rice.edu; urania@rice.edu; ma.tonys@va.gov; jwc@rice.edu FU Keck Center for Interdisciplinary Bioscience Training of the Gulf Coast Consortia [5T15LM07093] FX This work was supported by a training fellowship from the Keck Center for Interdisciplinary Bioscience Training of the Gulf Coast Consortia (NLM Grant No. 5T15LM07093). NR 50 TC 6 Z9 8 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4682 J9 THEOR BIOL MED MODEL JI Theor. Biol. Med. Model. PD AUG 6 PY 2009 VL 6 AR 15 DI 10.1186/1742-4682-6-15 PG 28 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 498WU UT WOS:000270177300001 PM 19656411 ER PT J AU Rollenhagen, JE Kalsy, A Saksena, R Sheikh, A Alam, MM Qadri, F Calderwood, SB Kovac, P Ryan, ET AF Rollenhagen, Julianne E. Kalsy, Anuj Saksena, Rina Sheikh, Alaullah Alam, Mohammad Murshid Qadri, Firdausi Calderwood, Stephen B. Kovac, Pavol Ryan, Edward T. TI Transcutaneous immunization with a synthetic hexasaccharide-protein conjugate induces anti-Vibrio cholerae lipopolysaccharide responses in mice SO VACCINE LA English DT Article DE Cholera; Transcutaneous immunization; Conjugate ID ADP-RIBOSYLATING EXOTOXINS; RURAL EAST PAKISTAN; INFLUENZAE TYPE-B; FIELD-TRIAL AREA; FREE MOUSE MODEL; PROTECTIVE IMMUNITY; ORAL IMMUNIZATION; IN-VIVO; ATTENUATED VACCINE; SEROLOGICAL SURVEY AB Antibodies specific for Vibrio cholerae lipopolysaccaricle (LPS) are common in humans recovering from cholera, and constitute a primary component of the vibriocidal response, a serum complement-mediated bacteriocidal response correlated with protection against cholera. In order to determine whether transcutaneous immunization (TCI) with a V cholerae neoglycoconjugate (CHO-BSA) comprised of a synthetic terminal hexasaccharide of the O-specific polysaccharide of V. cholerae O1 (Ogawa) conjugated with bovine serum albumin (BSA) could induce anti-V. cholerae LPS and vibriocidal responses, we applied CHO-BSA transcutaneously in the presence or absence of the immune adjuvant cholera toxin (CT) to mice. Transcutaneously applied neoglycoconjugate elicited prominent V cholerae specific LPS IgG responses in the presence of CT, but not IgM or IgA responses. CT applied on the skin induced strong IgG and IgA serum responses. TCI with neoglycoconjugate did not elicit detectable vibriocidal responses, protection in a mouse challenge assay, or stool anti-V. cholerae IgA responses, irrespective of the presence or absence of CT. Our results suggest that transcutaneously applied synthetic V. cholerae neoglycoconjugate is safe and immunogenic, but predominantly induces systemic LPS responses of the IgG isotype. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Rollenhagen, Julianne E.; Kalsy, Anuj; Sheikh, Alaullah; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Rollenhagen, Julianne E.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Saksena, Rina; Kovac, Pavol] NIDDK, LBC, Sect Carbohydrates, NIH, Bethesda, MD USA. [Sheikh, Alaullah; Alam, Mohammad Murshid; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Ctr, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM julianne.rollenhagen@med.navy.mil; etryan@partners.org FU National Institutes of Health; National Institute of Allergy & Infectious Diseases [AI067342, AI40725, AI058935]; Vaccine Development from the Fogarty International Center [TW05572] FX This work was supported by grants from the National Institutes of Health, including the National Institute of Allergy & Infectious Diseases (AI067342 [ETR], AI40725 [ETRI. AI058935 [SBC]), and a Training Grant in Vaccine Development from the Fogarty International Center (TW05572 [AS, FQ]). The authors would like to thank William F. Wade for helpful input. NR 43 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 6 PY 2009 VL 27 IS 36 BP 4917 EP 4922 DI 10.1016/j.vaccine.2009.06.040 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 484UA UT WOS:000269071800008 PM 19563890 ER PT J AU Walsh, SR Gillis, J Peters, B Mothe, BR Sidney, J Sette, A Johnson, RP AF Walsh, Stephen R. Gillis, Jacqueline Peters, Bjoern Mothe, Bianca R. Sidney, John Sette, Alessandro Johnson, R. Paul TI Diverse recognition of conserved orthopoxvirus CD8+T cell epitopes in vaccinated rhesus macaques SO VACCINE LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 12-15, 2006 CL Toronto, CANADA SP Infect Dis Soc Amer DE Vaccinia virus; T cell epitopes; Non-human primates ID MHC CLASS-I; SIMIAN IMMUNODEFICIENCY VIRUS; SMALLPOX VACCINE; PEPTIDE BINDING; T-CELLS; PROGRESSIVE VACCINIA; CYNOMOLGUS MACAQUES; ANTIBODY-RESPONSES; POXVIRUS INFECTION; NONHUMAN-PRIMATES AB Vaccinia virus (VACV) induces a vigorous virus-specific CD8+ T cell response that plays an important role in control of poxvirus infection. To identify immunodominant poxvirus proteins and to facilitate future testing of smallpox vaccines in non-human primates, we used an algorithm for the prediction of VACV peptides able to bind to the common macaque MHC class I molecule Mamu-A*01. We synthesized 294 peptides derived from 97 VACV ORFs; 100 of these peptides did not contain the canonical proline at position three of the Mamu-A*01 binding motif. Cellular immune responses in PBMC from two vaccinia-vaccinated Mamu-A*01+ macaques were assessed by IFN-gamma ELISPOT assays. Vaccinated macaques recognized 17 peptides from 16 different ORFs with 6 peptides recognized by both macaques. Comparison with other orthopoxvirus sequences revealed that 12 of these epitopes are strictly conserved between VACV, variola, and monkeypoxvirus. ELISPOT responses were also observed to eight epitopes that did not contain the canonical P3 proline. These results suggest that the virus-specific CD8+ T cell response is broadly directed against multiple VACV proteins and that a subset of these T cell epitopes is highly conserved among orthopoxviruses. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Walsh, Stephen R.; Gillis, Jacqueline; Johnson, R. Paul] Harvard Univ, New England Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. [Walsh, Stephen R.; Johnson, R. Paul] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Peters, Bjoern; Sidney, John; Sette, Alessandro] La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. [Mothe, Bianca R.] Calif State Univ, San Marcos, CA 92096 USA. RP Johnson, RP (reprint author), Harvard Univ, New England Primate Res Ctr, Sch Med, Div Immunol, Southborough Campus,Pine Hill Dr,1 Pine Hill Dr, Southborough, MA 01772 USA. EM paul_johnson@hms.harvard.edu FU NCRR NIH HHS [P51 RR000168-475599, K26 RR000168, P51 RR000168-466944, P51 RR000168-420142, P51 RR000168-466910, P51 RR000168-430156, P51 RR000168-440156, P51 RR000168-475627, P51 RR000168-455690, P51 RR000168]; NIAID NIH HHS [U54 AI057159, HHSH266200400006C, R15 AI064175-01, U54 AI057159-04, R15 AI064175, U54 AI057159-05, U54 AI057159-03]; PHS HHS [HHSH266200400006C] NR 84 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 6 PY 2009 VL 27 IS 36 BP 4990 EP 5000 DI 10.1016/j.vaccine.2009.05.077 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 484UA UT WOS:000269071800018 PM 19531389 ER PT J AU Walensky, RP Wolf, LL Wood, R Fofana, MO Freedberg, KA Martinson, NA Paltiel, AD Anglaret, X Weinstein, MC Losina, E AF Walensky, Rochelle P. Wolf, Lindsey L. Wood, Robin Fofana, Mariam O. Freedberg, Kenneth A. Martinson, Neil A. Paltiel, A. David Anglaret, Xavier Weinstein, Milton C. Losina, Elena CA CEPAC Int Investigators TI When to Start Antiretroviral Therapy in Resource-Limited Settings SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HIV-INFECTED PATIENTS; COTE-DIVOIRE; COST-EFFECTIVENESS; SOUTH-AFRICA; OPPORTUNISTIC INFECTIONS; OUTCOMES; IMPACT; RECOMMENDATIONS; TUBERCULOSIS; PROPHYLAXIS AB Background: The results of international clinical trials that are assessing when to initiate antiretroviral therapy (ART) will not be available for several years. Objective: To inform HIV treatment decisions about the optimal CD4 threshold at which to initiate ART in South Africa while awaiting the results of these trials. Design: Cost-effectiveness analysis by using a computer simulation model of HIV disease. Data Sources: Published data from randomized trials and observational cohorts in South Africa. Target Population: HIV-infected patients in South Africa. Time Horizon: 5-year and lifetime. Perspective: Modified societal. Intervention: No treatment, ART initiated at a CD4 count less than 0.250 x 10(9) cells/L, and ART initiated at a CD4 count less than 0.350 x 10(9) cells/L. Outcome Measures: Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness. Results of Base-Case Analysis: If 10% to 100% of HIV-infected patients are identified and linked to care, a CD4 count threshold for ART initiation of 0.350 x 10(9) cells/L would reduce severe opportunistic diseases by 22000 to 221000 and deaths by 25000 to 253000 during the next 5 years compared with ART initiation at 0.250 x 10(9) cells/L; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART initiation strategy would increase long-term survival by at least 7.9 years, with a mean per-person life expectancy of 3.8 years with no ART and 12.5 years with an initiation threshold of 0.350 x 10(9) cells/L. Compared with an initiation threshold of 0.250 x 10(9) cells/ L, a threshold of 0.350 x 10(9) cells/L has an incremental cost-effectiveness ratio of $1200 per year of life saved. Results of Sensitivity Analysis: Initiating ART at a CD4 count less than 0.350 x 10(9) cells/ L would remain cost-effective over the next 5 years even if the probability that the trial would demonstrate the superiority of earlier therapy is as low as 17%. Limitation: This model does not consider the possible benefits of initiating ART at a CD4 count greater than 0.350 x 10(9) cells/ L or of reduced HIV transmission. Conclusion: Earlier initiation of ART in South Africa will probably reduce morbidity and mortality, improve long-term survival, and be cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow initiation at CD4 counts less than 0.350 x 10(9) cells/ L, earlier than is currently recommended. Primary Funding Source: National Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Gen Hosp,Sch Publ Hlth, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Univ Cape Town, ZA-7925 Cape Town, South Africa. Perinatal HIV Res Unit, Johannesburg, South Africa. Johns Hopkins Univ, Baltimore, MD USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Bordeaux 2, Bordeaux, France. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. RI Wood, Robin/G-8509-2011; Anglaret, Xavier/F-7333-2013; OI Fofana, Mariam/0000-0002-2874-471X FU National Institute of Allergy and Infectious Diseases [R01 AI058736, K24 AI062476, P30 AI060354, U01 AI068634]; Doris Duke Charitable Foundation FX Grant Support: By the National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, P30 AI060354, and U01 AI068634) and the Doris Duke Charitable Foundation (Clinical Scientist Development Award). NR 46 TC 98 Z9 100 U1 0 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 4 PY 2009 VL 151 IS 3 BP 157 EP W38 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 483FM UT WOS:000268947800002 PM 19620143 ER PT J AU Turenius, CI Charles, JR Tsai, DH Ebersole, PL Htut, MH Ngo, PT Lara, RN Stanley, BG AF Turenius, Christine I. Charles, Jonathan R. Tsai, Donna H. Ebersole, Priscilla L. Htut, Myat H. Ngo, Phuong T. Lara, Raul N. Stanley, B. Glenn TI The tuberal lateral hypothalamus is a major target for GABA(A)- but not GABA(B)-mediated control of food intake SO BRAIN RESEARCH LA English DT Article DE Feeding; Inhibition; GABA; Receptor; Lateral Hypothalamus; Rat ID BODY-WEIGHT; INGESTIVE BEHAVIOR; LOCOMOTOR-ACTIVITY; DORSOMEDIAL HYPOTHALAMUS; FEEDING-BEHAVIOR; RAT HYPOTHALAMUS; ARCUATE NUCLEUS; NEURONS; RECEPTORS; ACID AB The lateral hypothalamus (LH) is a site of integration for control mechanisms of feeding behavior as it has extensive reciprocal connections with multiple intrahypothalamic and extrahypothalamic brain areas. Evidence suggests that blockade of ionotropric gamma-aminobutyric acid (GABA) receptors in the LH elicits eating in satiated rats. To determine whether this GABA(A) receptor antagonist effect is specific to the LH, the antagonist picrotoxin was injected into one of six nearby sites and food intake was measured. Picrotoxin at 133 pmol elicited eating in the LH, but not in surrounding sites (thalamus, lateral preoptic area, ventral tegmental area, dorsomedial hypothalamus, and entopeduncular nucleus). More specifically, picrotoxin injected into the tuberal LH (tLH) elicited eating, but was ineffective when injected into the anterior or posterior LH. We also investigated whether GABA(B) receptors in the LH participated in the control of food intake and found that neither blockade nor activation of these receptors under multiple conditions changed food intake. Collectively, our findings suggest that GABAA but not GABAB receptors in the tLH act to suppress feeding behavior. Published by Elsevier B.V. C1 [Turenius, Christine I.; Charles, Jonathan R.; Stanley, B. Glenn] Univ Calif Riverside, Interdepartmental Neurosci Grad Program, Riverside, CA 92521 USA. [Tsai, Donna H.; Ebersole, Priscilla L.; Htut, Myat H.; Ngo, Phuong T.; Lara, Raul N.; Stanley, B. Glenn] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. [Stanley, B. Glenn] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA. RP Turenius, CI (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,R-151, Seattle, WA 98108 USA. EM turenius@u.washington.edu OI Charles, Jonathan/0000-0002-1598-0801 NR 51 TC 15 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 4 PY 2009 VL 1283 BP 65 EP 72 DI 10.1016/j.brainres.2009.05.064 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 484FQ UT WOS:000269029700008 PM 19501070 ER PT J AU Jackson, ML Ferencz, J AF Jackson, M. L. Ferencz, Joseph TI Charles Bonnet syndrome: visual loss and hallucinations SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material ID VISION LOSS C1 [Jackson, M. L.] Massachusetts Eye & Ear Infirm, Harvard Dept Ophthalmol, Boston, MA 02114 USA. [Ferencz, Joseph] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. RP Jackson, ML (reprint author), Massachusetts Eye & Ear Infirm, Harvard Dept Ophthalmol, Boston, MA 02114 USA. NR 16 TC 8 Z9 8 U1 0 U2 5 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD AUG 4 PY 2009 VL 181 IS 3-4 BP 175 EP 176 DI 10.1503/cmaj.090049 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 474SW UT WOS:000268305300014 PM 19652169 ER PT J AU Croce, K Gao, HY Wang, YM Mooroka, T Sakuma, M Shi, C Sukhova, GK Packard, RRS Hogg, N Libby, P Simon, DI AF Croce, Kevin Gao, Huiyun Wang, Yunmei Mooroka, Toshifumi Sakuma, Masashi Shi, Can Sukhova, Galina K. Packard, Rene R. S. Hogg, Nancy Libby, Peter Simon, Daniel I. TI Myeloid-Related Protein-8/14 Is Critical for the Biological Response to Vascular Injury SO CIRCULATION LA English DT Article DE atherosclerosis; inflammation; leukocytes; restenosis; vasculitis ID TRANSENDOTHELIAL MIGRATION; INNATE IMMUNITY; SHWARTZMAN REACTION; ENDOTHELIAL-CELLS; ARACHIDONIC-ACID; INTEGRIN MAC-1; MICE REVEALS; NULL MICE; S100A9; ATHEROSCLEROSIS AB Background-Myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) are members of the S100 family of calcium-modulated proteins that regulate myeloid cell function and control inflammation, in part, through activation of Toll-like receptor-4 and the receptor for advanced glycation end products. A transcriptional profiling approach in patients with acute coronary syndromes identified MRP-14 as a novel predictor of myocardial infarction. Further studies demonstrated that elevated plasma levels of MRP-8/14 heterodimer predict increased risk of first and recurrent cardiovascular events. Beyond its serving as a risk marker, whether MRP-8/14 participates directly in vascular inflammation and disease remains unclear. Methods and Results-We evaluated vascular inflammation in wild-type and MRP-14-deficient (MRP-14(-/-)) mice that lack MRP-8/14 complexes with experimental arterial injury, vasculitis, or atherosclerosis. After femoral artery wire injury, MRP-14(-/-) mice had significant reductions in leukocyte accumulation, cellular proliferation, and neointimal formation compared with wild-type mice. In a cytokine-induced local Shwartzman-like reaction that produces thrombohemorrhagic vasculitis, MRP-14(-/-) mice had significant reductions in neutrophil accumulation, lesion severity, and hemorrhagic area. In response to high-fat feeding, mice doubly deficient in apolipoprotein E and MRP-8/14 complexes had attenuation in atherosclerotic lesion area and in macrophage accumulation in plaques compared with mice deficient in apolipoprotein E alone. Conclusion-This study demonstrates that MRP-8/14 broadly regulates vascular inflammation and contributes to the biological response to vascular injury by promoting leukocyte recruitment. (Circulation. 2009;120:427-436.) C1 [Croce, Kevin; Gao, Huiyun; Wang, Yunmei; Mooroka, Toshifumi; Sakuma, Masashi; Shi, Can; Simon, Daniel I.] Case Western Reserve Univ, Sch Med, Case Cardiovasc Ctr, Univ Hosp,Case Med Ctr, Cleveland, OH 44106 USA. [Croce, Kevin; Sukhova, Galina K.; Packard, Rene R. S.; Libby, Peter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Donald W Reynolds Cardiovasc Clin Res Ct, Boston, MA 02115 USA. [Hogg, Nancy] Canc Res UK, London, England. [Croce, Kevin] VA Boston Healthcare Syst, Boston, MA USA. RP Simon, DI (reprint author), Case Western Reserve Univ, Sch Med, Case Cardiovasc Ctr, Div Cardiovasc Med, 11100 Euclid Ave,LKS 3001, Cleveland, OH 44106 USA. EM Daniel.Simon@UHhospitals.org OI Packard, Rene/0000-0002-8520-5843 FU National Heart, Lung, and Blood Institute [HL85816, HL57506, HL73852] FX This work was supported in part by grants from the National Heart, Lung, and Blood Institute to Dr Simon (HL85816, HL57506 MERIT Award, HL73852), to Dr Croce (1K08HL086672), and to Dr Libby (HL34636); the Donald W. Reynolds Foundation to Dr Libby; a Future Leaders in Cardiovascular Medicine Fellowship Grant from Schering Plough to Dr Croce; and an award from the Michael Lerner Foundation to Dr Croce. NR 47 TC 111 Z9 119 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 4 PY 2009 VL 120 IS 5 BP 427 EP U126 DI 10.1161/CIRCULATIONAHA.108.814582 PG 24 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 479DA UT WOS:000268638700014 PM 19620505 ER PT J AU Patel, SJ King, KR Casali, M Yarmush, ML AF Patel, Suraj J. King, Kevin R. Casali, Monica Yarmush, Martin L. TI DNA-triggered innate immune responses are propagated by gap junction communication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE innate immunity; IRF; TLR; interferon ID REGULATORY FACTOR FAMILY; INTERCELLULAR COMMUNICATION; ANTIVIRAL RESPONSE; MAMMALIAN-CELLS; GENE-EXPRESSION; VIRAL-INFECTION; AIRWAY CELLS; RECOGNITION; PERMEABILITY; CHANNELS AB Cells respond to infection by sensing pathogens and communicating danger signals to noninfected neighbors; however, little is known about this complex spatiotemporal process. Here we show that activation of the innate immune system by double-stranded DNA (dsDNA) triggers intercellular communication through a gap junction-dependent signaling pathway, recruiting colonies of cells to collectively secrete antiviral and inflammatory cytokines for the propagation of danger signals across the tissue at large. By using live-cell imaging of a stable IRF3-sensitive GFP reporter, we demonstrate that dsDNA sensing leads to multicellular colonies of IRF3-activated cells that express the majority of secreted cytokines, including IFN beta and TNF alpha. Inhibiting gap junctions decreases dsDNA-induced IRF3 activation, cytokine production, and the resulting tissue-wide antiviral state, indicating that this immune response propagation pathway lies upstream of the paracrine action of secreted cytokines and may represent a host-derived mechanism for evading viral antiinterferon strategies. C1 [Yarmush, Martin L.] Shriners Burns Hosp, Massachusetts Gen Hosp, Ctr Engn Med, Dept Surg, Boston, MA 02114 USA. [Patel, Suraj J.; King, Kevin R.; Yarmush, Martin L.] Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Patel, Suraj J.; King, Kevin R.; Casali, Monica; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Shriners Burns Hosp, Massachusetts Gen Hosp, Ctr Engn Med, Dept Surg, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU U.S. National Institutes of Health [GM065474, P41 EB-002503]; Shriners Hospital for Children FX We thank S. Akira (Osaka University, Osaka, Japan) for the generous gift of Myd88-/-Trif-/- and Tbk-/-Ikke-/- MEFs; I. Verma (The Salk Institute of Biological Studies, La Jolla, CA) for Ikka-/-Ikkb-/- MEFs; S. L. Friedman (Duke University, Durham, NC) for HSC-T6 cells; D. Spray (Albert Einstein College of Medicine, New York) for Cx26-, Cx32-, and Cx43-expressing N2A cells; and K. Willecke (University of Bonn, Bonn, Germany) for Cx26-, Cx32-, and Cx43-expressing HeLa cells. The authors thank Ken Wieder and Arno Tilles for technical support. S. J. P was supported by a Department of Defense Congressionally directed medical research program Prostate Cancer Predoctoral Training Award. K. R. K was supported by a Shriners Hospital for Children postdoctoral fellowship. The work was supported by U.S. National Institutes of Health Grants GM065474 and P41 EB-002503, and by a grant from the Shriners Hospital for Children. NR 29 TC 21 Z9 21 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 4 PY 2009 VL 106 IS 31 BP 12867 EP 12872 DI 10.1073/pnas.0809292106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 479NT UT WOS:000268667600056 PM 19617563 ER PT J AU Yoo, BK Gredler, R Vozhilla, N Su, ZZ Chen, D Forcier, T Shah, K Saxena, U Hansen, U Fisher, PB Sarkar, D AF Yoo, Byoung Kwon Gredler, Rachel Vozhilla, Nicollaq Su, Zao-zhong Chen, Dong Forcier, Talitha Shah, Khalid Saxena, Utsav Hansen, Ulla Fisher, Paul B. Sarkar, Devanand TI Identification of genes conferring resistance to 5-fluorouracil SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 5-FU; AEG-1; chemoresistance; DPYD; LSF ID ASTROCYTE-ELEVATED GENE-1; UNRESECTABLE HEPATOCELLULAR-CARCINOMA; IMMUNODEFICIENCY-VIRUS TYPE-1; TRANSCRIPTION FACTOR CP2; DIHYDROPYRIMIDINE DEHYDROGENASE; NUCLEAR-FACTOR; COMBINATION CHEMOTHERAPY; THYMIDYLATE SYNTHASE; CANCER PROGRESSION; COLORECTAL-CANCER AB Astrocyte elevated gene-1 (AEG-1) is overexpressed in >90% of human hepatocellular carcinoma (HCC) patients and plays a significant role in mediating aggressive progression of HCC. AEG-1 is known to augment invasion, metastasis, and angiogenesis, and we now demonstrate that AEG-1 directly contributes to another important hallmark of aggressive cancers, that is, resistance to chemotherapeutic drugs, such as 5-fluorouracil (5-FU). AEG-1 augments expression of the transcription factor LSF that regulates the expression of thymidylate synthase (TS), a target of 5-FU. In addition, AEG-1 enhances the expression of dihydropyrimidine dehydrogenase (DPYD) that catalyzes the initial and rate-limiting step in the catabolism of 5-FU. siRNA-mediated inhibition of AEG-1, LSF, or DPYD significantly increased the sensitivity of HCC cells to 5-FU in vitro and a lentivirus delivering AEG-1 siRNA in combination with 5-FU markedly inhibited growth of HCC cells xenotransplanted in athymic nude mice when compared to either agent alone. The present studies highlight 2 previously unidentified genes, AEG-1 and LSF, contributing to chemoresistance. Inhibition of AEG-1 might be exploited as a therapeutic strategy along with 5-FU-based combinatorial chemotherapy for HCC, a highly fatal cancer with currently very limited therapeutic options. C1 [Yoo, Byoung Kwon; Gredler, Rachel; Vozhilla, Nicollaq; Su, Zao-zhong; Chen, Dong; Fisher, Paul B.; Sarkar, Devanand] Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA 23298 USA. [Fisher, Paul B.; Sarkar, Devanand] Virginia Commonwealth Univ, Sch Med, Inst Mol Med, Richmond, VA 23298 USA. [Fisher, Paul B.; Sarkar, Devanand] Virginia Commonwealth Univ, Sch Med, Massey Canc Ctr, Richmond, VA 23298 USA. [Forcier, Talitha; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neuropathy & Imaging Lab,Dept Radiol, Boston, MA 02115 USA. [Forcier, Talitha; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neuropathy & Imaging Lab,Dept Neurol, Boston, MA 02115 USA. [Saxena, Utsav; Hansen, Ulla] Boston Univ, Dept Biol, Boston, MA 02215 USA. RP Sarkar, D (reprint author), 401 Coll St,POB 980035, Richmond, VA 23298 USA. EM dsarkar@vcu.edu RI chen, dong/A-6889-2012 FU Dana Foundation; National Institutes of Health [P01 NS31492, R01 CA035675] FX The present study was supported in part by a Goldhirsh Foundation grant and a Dana Foundation grant (to D. S.) and National Institutes of Health Grants P01 NS31492 and R01 CA035675 (to P.B.F.). D.S. is the Harrison Endowed Scholar in Cancer Research. P. B. F. holds the Thelma Newmeyer Corman Chair in Cancer Research and is a Samuel Waxman Cancer Research Foundation Investigator. NR 51 TC 83 Z9 91 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 4 PY 2009 VL 106 IS 31 BP 12938 EP 12943 DI 10.1073/pnas.0901451106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 479NT UT WOS:000268667600068 PM 19622726 ER PT J AU Schleicher, M Yu, J Murata, T Derakhshan, B Atochin, D Qian, L Kashiwagi, S Di Lorenzo, A Harrison, KD Huang, PL Sessa, WC AF Schleicher, Michael Yu, Jun Murata, Takahisa Derakhshan, Berhad Atochin, Dimitriy Qian, Li Kashiwagi, Satoshi Di Lorenzo, Annarita Harrison, Kenneth D. Huang, Paul L. Sessa, William C. TI The Akt1-eNOS Axis Illustrates the Specificity of Kinase-Substrate Relationships in Vivo SO SCIENCE SIGNALING LA English DT Article ID NITRIC-OXIDE SYNTHASE; HYPOXIA-INDUCIBLE FACTOR; ENDOTHELIAL-SPECIFIC EXPRESSION; VEGF-MEDIATED ANGIOGENESIS; S-NITROSYLATION; PATHOLOGICAL ANGIOGENESIS; VASCULAR MATURATION; AKT; PHOSPHORYLATION; OXYGEN AB Akt1 is critical for many in vivo functions; however, the cell-specific substrates responsible remain to be defined. Here, we examine the importance of endothelial nitric oxide synthase (eNOS) as an Akt1 substrate by generating Akt1-deficient mice (Akt1(-/-) mice) carrying knock-in mutations (serine to aspartate or serine to alanine substitutions) of the critical Akt1 phosphorylation site on eNOS (serine 1176) that render the enzyme "constitutively active" or "less active." The eNOS mutations did not influence several phenotypes in Akt1(-/-) mice; however, the defective postnatal angiogenesis characteristic of Akt1(-/-) mice was rescued by crossing the Akt1(-/-) mice with mice carrying the constitutively active form of eNOS, but not by crossing with mice carrying the less active eNOS mutant. This genetic rescue resulted in the stabilization of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and increased production of HIF-1 alpha-responsive genes in vivo and in vitro. Thus, Akt1 regulates angiogenesis largely through phosphorylation of eNOS and NO-dependent signaling. C1 [Atochin, Dimitriy; Qian, Li; Kashiwagi, Satoshi; Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. [Schleicher, Michael; Yu, Jun; Derakhshan, Berhad; Di Lorenzo, Annarita; Harrison, Kenneth D.; Sessa, William C.] Yale Univ, Sch Med, Dept Pharmacol & Vasc Biol, New Haven, CT 06520 USA. [Schleicher, Michael; Yu, Jun; Derakhshan, Berhad; Di Lorenzo, Annarita; Harrison, Kenneth D.; Sessa, William C.] Yale Univ, Sch Med, Therapeut Program, New Haven, CT 06520 USA. [Murata, Takahisa] Univ Tokyo, Dept Vet Pharmacol, Grad Sch Agr & Life Sci, Bunkyo Ku, Tokyo 1138657, Japan. [Atochin, Dimitriy; Qian, Li; Kashiwagi, Satoshi; Huang, Paul L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02129 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. EM huangp@helix.mgh.harvard.edu; william.sessa@yale.edu RI Sessa, William/B-6844-2011; Atochin, Dmitriy/Q-3150-2016 FU NHLBI NIH HHS [R01 HL064793-12, N01HV28186, P01 HL070295, R01 HL057665, R01 HL061371, R01 HL064793, R01 HL081190, R01 HL081190-07, R01 HL096670, R01 HL096670-02, R37 HL061371, R37 HL061371-13]; NINDS NIH HHS [R01 NS033335] NR 46 TC 43 Z9 44 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD AUG 4 PY 2009 VL 2 IS 82 AR ra41 DI 10.1126/scisignal.2000343 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 569MN UT WOS:000275601300003 PM 19654415 ER PT J AU Jasti, H Hanusa, BH Switzer, GE Granieri, R Elnicki, M AF Jasti, Harish Hanusa, Barbara H. Switzer, Galen E. Granieri, Rosanne Elnicki, Michael TI Residents' perceptions of a night float system SO BMC MEDICAL EDUCATION LA English DT Article ID INTERNAL-MEDICINE RESIDENTS; PATIENT-CARE; HOUSE STAFF; SLEEP-DEPRIVATION; CALL STRUCTURE; WORKING HOURS; IMPACT; RESPONSIBILITY; SATISFACTION; PERFORMANCE AB Background: A Night Float (NF) system has been implemented by many institutions to address increasing concerns about residents' work hours. The purpose of our study was to examine the perceptions of residents towards a NF system. Methods: A 115-item questionnaire was developed to assess residents' perceptions of the NF rotation as compared with a regular call month. The categories included patient care, education, medical errors, and overall satisfaction. Internal Medicine housestaff (post-graduate years 1-3) from three hospital settings at the University of Pittsburgh completed the questionnaire. Results: The response rate was 90% (n = 149). Of these, 74 had completed the NF rotation. The housestaff felt that the quality of patient care was improved because of NF (41% agreed and 18% disagreed). A majority also felt that better care was provided by a rested physician in spite of being less familiar with the patient (46% agreed and 21% disagreed). Most felt that there was less emphasis on education (65%) and more emphasis on service (52%) during NF. Overall, the residents felt more rested during their call months (83%) and strongly supported the 80-hour workweek requirement (77%). Conclusion: Housestaff felt that the overall quality of patient care was improved by a NF system. The perceived improved quality of care by a rested physician coupled with a perceived decrease in the emphasis on education may have significant implications in housestaff training. C1 [Jasti, Harish; Granieri, Rosanne; Elnicki, Michael] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. [Hanusa, Barbara H.; Switzer, Galen E.] Univ Pittsburgh, VA Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hanusa, Barbara H.; Switzer, Galen E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. RP Jasti, H (reprint author), Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. EM jastih@upmc.edu; hanusab@upmc.edu; switzerg@upmc.edu; granierir@upmc.edu; elnickim@upmc.edu NR 26 TC 15 Z9 15 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6920 J9 BMC MED EDUC JI BMC Med. Educ. PD AUG 3 PY 2009 VL 9 AR 52 DI 10.1186/1472-6920-9-52 PG 6 WC Education & Educational Research; Education, Scientific Disciplines SC Education & Educational Research GA 686RB UT WOS:000284712300001 PM 19650924 ER PT J AU Park, J Kemp, NJ Rylander, HG Milner, TE AF Park, Jesung Kemp, Nate J. Rylander, H. Grady, III Milner, Thomas E. TI Complex polarization ratio to determine polarization properties of anisotropic tissue using polarization-sensitive optical coherence tomography SO OPTICS EXPRESS LA English DT Article ID NERVE-FIBER LAYER; AXIS ORIENTATION; MUELLER MATRIX; TURBID MEDIA; HUMAN SKIN; PS-OCT; BIREFRINGENCE; MODULATION; COLLAGEN; RETINA AB Complex polarization ratio (CPR) in materials with birefringence and biattenuance is shown as a logarithmic spiral in the complex plane. A multi-state Levenberg-Marquardt nonlinear fitting algorithm using the CPR trajectory collected by polarization sensitive optical coherence tomography (PS-OCT) was developed to determine polarization properties of an anisotropic scattering medium. The Levenberg-Marquardt nonlinear fitting algorithm using the CPR trajectory is verified using simulated PS-OCT data with speckle noise. Birefringence and biattenuance of a birefringent film, ex-vivo rodent tail tendon and in-vivo primate retinal nerve fiber layer were determined using measured CPR trajectories and the Levenberg-Marquardt nonlinear fitting algorithm. (C) 2009 Optical Society of America C1 [Park, Jesung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kemp, Nate J.; Rylander, H. Grady, III; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. RP Park, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. EM empstar@gmail.com FU Texas Higher Education Coordinating Board Advanced Technology Program; National Institutes of Health [R01 EY 016462-04] FX The authors gratefully acknowledge the Texas Higher Education Coordinating Board Advanced Technology Program and the National Institutes of Health for financial support of this research (R01 EY 016462-04). NR 32 TC 5 Z9 6 U1 2 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD AUG 3 PY 2009 VL 17 IS 16 BP 13402 EP 13417 DI 10.1364/OE.17.013402 PG 16 WC Optics SC Optics GA 481WQ UT WOS:000268843700015 PM 19654746 ER PT J AU Ladiges, W Van Remmen, H Strong, R Ikeno, Y Treuting, P Rabinovitch, P Richardson, A AF Ladiges, Warren Van Remmen, Holly Strong, Randy Ikeno, Yuji Treuting, Piper Rabinovitch, Peter Richardson, Arlan TI Lifespan extension in genetically modified mice SO AGING CELL LA English DT Review ID NEMATODE CAENORHABDITIS-ELEGANS; FATAL NEOPLASTIC DISEASES; AMES DWARF MICE; OXIDATIVE STRESS; DETERMINANT P66(SHC); DIETARY RESTRICTION; EXTENDED LONGEVITY; DELAYED OCCURRENCE; KNOCKOUT MICE; F1 HYBRIDS AB P>Major advances in aging research have been made by studying the effect of genetic modifications on the lifespan of organisms, such as yeast, invertebrates (worms and flies) and mice. Data from yeast and invertebrates have been the most plentiful because of the ease in which genetic manipulations can be made and the rapidity by which lifespan experiments can be performed. With the ultimate focus on advancing human health, testing genetic interventions in mammals is crucial, and the mouse has proven to be the mammal most amenable to this task. Lifespan studies in mice are resource intensive, requiring up to 4 years to complete. Therefore, it is critical that a set of scientifically-based criteria be followed to assure reliable results and establish statistically significant findings so other laboratories can replicate and build on the data. Only then will it be possible to confidently determine that the genetic modification extends lifespan and alters aging. C1 [Ladiges, Warren; Treuting, Piper] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA. [Van Remmen, Holly; Strong, Randy; Ikeno, Yuji; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78245 USA. [Van Remmen, Holly; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Van Remmen, Holly; Strong, Randy; Ikeno, Yuji; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78245 USA. [Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78245 USA. [Rabinovitch, Peter] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. RP Ladiges, W (reprint author), Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA. EM wladiges@u.washington.edu NR 53 TC 53 Z9 53 U1 0 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD AUG PY 2009 VL 8 IS 4 BP 346 EP 352 DI 10.1111/j.1474-9726.2009.00491.x PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 473NH UT WOS:000268213300001 PM 19485964 ER PT J AU Mimiaga, MJ Reisner, SL Tetu, AM Cranston, K Bertrand, T Novak, DS Mayer, KH AF Mimiaga, Matthew J. Reisner, Sari L. Tetu, Ashley M. Cranston, Kevin Bertrand, Thomas Novak, David S. Mayer, Kenneth H. TI Psychosocial and Behavioral Predictors of Partner Notification After HIV and STI Exposure and Infection Among MSM SO AIDS AND BEHAVIOR LA English DT Article DE MSM; HIV; Sexually transmitted infection; Partner notification ID SEXUALLY-TRANSMITTED-DISEASES; HOMOSEXUALLY ACTIVE MEN; CAGE QUESTIONNAIRE; RISK BEHAVIORS; SEX; PREVENTION; HEALTH; COHORT; SURVEILLANCE; ALCOHOLISM AB Partner notification (PN) is an essential element of local and state-level HIV/STI prevention and control programs. The current study quantitatively assessed the psychosocial and behavioral predictors of PN use among men who have sex with men (MSM) (n = 189) using multivariable logistic regression procedures. STI history or being HIV-infected were significant predictors of having notified past sexual partners of HIV/STI exposure; engaging in unprotected insertive anal sex and using poppers during sex in the 12 months prior to enrollment resulted in greater odds of PN. Symptoms of social anxiety and having a drinking problem were significant predictors of future willingness to use state department of public health PN services. Efforts to increase PN acceptability should focus on HIV-uninfected MSM, particularly those with STI history. Results suggest how to increase acceptability and use of PN as a public health strategy and underscore the need for counseling as part of the notification process. C1 [Mimiaga, Matthew J.; Reisner, Sari L.; Tetu, Ashley M.; Mayer, Kenneth H.] Fenway Community Hlth, Fenway Inst, Boston, MA 02119 USA. [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Tetu, Ashley M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Cranston, Kevin; Bertrand, Thomas; Novak, David S.] Massachusetts Dept Publ Hlth, Boston, MA USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. RP Mimiaga, MJ (reprint author), Fenway Community Hlth, Fenway Inst, Prudential Tower,4th Floor,800 Boylston St, Boston, MA 02119 USA. EM mmimiaga@fenwayhealth.org NR 54 TC 10 Z9 10 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD AUG PY 2009 VL 13 IS 4 BP 738 EP 745 DI 10.1007/s10461-008-9424-y PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 476WS UT WOS:000268478000015 PM 18636324 ER PT J AU Reisner, SL Mimiaga, MJ Skeer, M Bright, D Cranston, K Isenberg, D Bland, S Barker, TA Mayer, KH AF Reisner, Sari L. Mimiaga, Matthew J. Skeer, Margie Bright, Donna Cranston, Kevin Isenberg, Deborah Bland, Sean Barker, Thomas A. Mayer, Kenneth H. TI Clinically Significant Depressive Symptoms as a Risk Factor for HIV Infection Among Black MSM in Massachusetts SO AIDS AND BEHAVIOR LA English DT Article DE MSM; Depression; African American; HIV; STD ID AFRICAN-AMERICAN MEN; ALCOHOL-RELATED PROBLEMS; HOMOSEXUALLY ACTIVE MEN; SEXUAL RISK; PSYCHOSOCIAL PREDICTORS; CAGE QUESTIONNAIRE; UNITED-STATES; GAY MEN; BISEXUAL POPULATIONS; 12-MONTH PREVALENCE AB High rates of depression have been observed among men who have sex with men (MSM) relative to the general adult male population; however, a dearth of research has explored depression among Black MSM. Black MSM (n = 197) recruited via modified respondent-driven sampling between January and July 2008 completed an interviewer-administered quantitative assessment and voluntary HIV counseling and testing. Bivariate and multivariable logistic regression procedures examined the associations of demographics, behavioral HIV risk factors, and psychosocial variables with depressive symptoms by severity, using the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Adjusting for demographic and behavioral variables, significant factors associated with (1) clinically significant depressive symptoms (33%; CES-D score a parts per thousand yen 16): being publicly insured by Medicaid, having serodiscordant anal sex with a casual male partner, and being diagnosed with an STD in the prior 12 months; (2) moderate depressive symptoms (19%; CES-D score 16-26): having serodiscordant unprotected anal sex with a casual male partner and being diagnosed with an STD in the prior 12 months; (3) severe depressive symptoms (14%; CES-D score 27+): being publicly insured by Medicaid and reporting difficulty accessing healthcare in the past 12 months. Moderately depressed Black MSM may be more likely to engage in behaviors that place them at increased risk for HIV and other STDs. HIV prevention interventions for Black MSM may benefit from incorporating screening and/or treatment for depression, allowing MSM who are depressed to respond more effectively to behavioral change approaches. C1 [Reisner, Sari L.; Mimiaga, Matthew J.; Skeer, Margie; Bland, Sean; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Skeer, Margie] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bright, Donna] Justice Resource Inst, Boston, MA USA. [Cranston, Kevin; Isenberg, Deborah; Barker, Thomas A.] Massachusetts Dept Publ Hlth, Boston, MA USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. RP Mimiaga, MJ (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St,8th Floor, Boston, MA 02215 USA. EM sreisner@fenwayhealth.org; mmimiaga@fenwayhealth.org FU NIDA NIH HHS [R03 DA023393, R03DA023393] NR 77 TC 44 Z9 48 U1 2 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD AUG PY 2009 VL 13 IS 4 BP 798 EP 810 DI 10.1007/s10461-009-9571-9 PG 13 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 476WS UT WOS:000268478000020 PM 19462228 ER PT J AU Salomon, EA Mimiaga, MJ Husnik, MJ Welles, SL Manseau, MW Montenegro, AB Safren, SA Koblin, BA Chesney, MA Mayer, KH AF Salomon, Elizabeth A. Mimiaga, Matthew J. Husnik, Marla J. Welles, Seth L. Manseau, Marc W. Montenegro, Arnel B. Safren, Steven A. Koblin, Beryl A. Chesney, Margaret A. Mayer, Kenneth H. TI Depressive Symptoms, Utilization of Mental Health Care, Substance Use and Sexual Risk Among Young Men Who have Sex with Men in EXPLORE: Implications for Age-Specific Interventions SO AIDS AND BEHAVIOR LA English DT Article DE MSM; HIV; Young men; Mental health; Substance use; Sexual behavior ID HIGH-SCHOOL-STUDENTS; BASE-LINE DATA; HIV-INFECTION; SUICIDE ATTEMPTS; SHORT-FORM; DRUG-USE; CES-D; UNITED-STATES; BISEXUAL MEN; BEHAVIORS AB The EXPLORE study evaluated a behavioral intervention to prevent HIV infection among MSM. We examined depressive symptoms, utilization of mental health care, substance use and HIV risk taking behaviors in YMSM aged 16-25 years compared with their older counterparts. YMSM were more likely to report depressive symptoms (OR = 1.55) and less likely to report use of counseling (OR = 0.39) or medication (OR = 0.20) for psychiatric conditions. YMSM were more likely to report heavy alcohol and drug use. YMSM more often reported engaging in unprotected insertive (OR = 1.60) and receptive (OR = 2.07) anal intercourse with presumed HIV-uninfected partners, and unprotected receptive (OR = 1.72) anal intercourse with partners of unknown-HIV status. These findings suggest the need for more appropriate and accessible mental health care and substance use services for YMSM. Additionally, HIV prevention work with this population should provide comprehensive education about HIV testing and risk reduction counseling that focuses on communication about serostatus and safety in sexual situations. C1 [Salomon, Elizabeth A.] Massachusetts Gen Hosp, Clin Res Program, Boston, MA 02115 USA. [Salomon, Elizabeth A.; Mimiaga, Matthew J.; Safren, Steven A.; Mayer, Kenneth H.] Fenway Community Hlth, Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Husnik, Marla J.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. [Welles, Seth L.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. [Manseau, Marc W.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Montenegro, Arnel B.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Koblin, Beryl A.] New York Blood Ctr, New York, NY 10021 USA. [Chesney, Margaret A.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Chesney, Margaret A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Providence, RI USA. RP Salomon, EA (reprint author), Massachusetts Gen Hosp, Clin Res Program, 185 Cambridge St CPZN 2-128, Boston, MA 02115 USA. EM esalomon@partners.org OI Manseau, Marc/0000-0002-3433-3562 FU NCI NIH HHS [N01 CA035176]; NIAID NIH HHS [N01 AI45200, U01 AI046749, U01 AI47981, 5 U01 AI46749, U01 AI48040, U01 AI48016, U01 AI47995, U01 AI047981, N01 AI35176, N01 AI045200, U01 AI047995, U01 AI048016, U01 AI048040, U01 AI069466, U01 AI069466-02]; NIDA NIH HHS [R01 DA032100] NR 60 TC 48 Z9 51 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD AUG PY 2009 VL 13 IS 4 BP 811 EP 821 DI 10.1007/s10461-008-9439-4 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 476WS UT WOS:000268478000021 PM 18709453 ER PT J AU Reisner, SL Mimiaga, MJ Skeer, M VanDerwarker, R Gaucher, MJ O'Connor, CA Medeiros, MS Safren, SA AF Reisner, Sari L. Mimiaga, Matthew J. Skeer, Margie VanDerwarker, Rodney Gaucher, Michael J. O'Connor, Catherine A. Medeiros, M. Susana Safren, Steven A. TI Differential HIV Risk Behavior among Men who have Sex with Men Seeking Health-Related Mobile Van Services at Diverse Gay-Specific Venues SO AIDS AND BEHAVIOR LA English DT Article DE HIV; STIs; MSM; Gay-venues ID MULTICENTER AIDS COHORT; BASE-LINE DATA; BISEXUAL MEN; POSITIVE MEN; YOUNG MEN; TRANSMISSION RISK; URBAN CENTERS; UNITED-STATES; SUBSTANCE USE; LOS-ANGELES AB Distinguishing between gay venues may provide important information to better understand patterns of environmental influence and HIV/STI behavioral risk among MSM. Massachusetts MSM accessing State Health Department mobile van services (n = 214) at Gay Pride events, bars/clubs, and private safer sex parties completed a one-time, cross-sectional survey via ACASI. In the past 12 months, private safer sex party attendees reported a higher mean number of anonymous partners, were more likely to report meeting sex partners via the Internet, and were more likely to report sex while drunk; in logistic regression analyses, they were less likely to report both unprotected insertive and receptive anal sex in the past year relative to men from other venues. Private safer sex parties may represent a strategy used by some MSM to reduce HIV/STI risk. Differentiating risk behavior by venue type provides valuable information with which to effectively target interventions to reach MSM at greatest risk. C1 [Reisner, Sari L.; Mimiaga, Matthew J.; Skeer, Margie; VanDerwarker, Rodney; Safren, Steven A.] Fenway Community Hlth, Fenway Inst, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Skeer, Margie] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gaucher, Michael J.] Massachusetts Dept Publ Hlth, HIV AIDS Bur, Boston, MA USA. [O'Connor, Catherine A.] Northeastern Univ, Bouve Coll Hlth Sci, Sch Nursing, Boston, MA 02115 USA. [Medeiros, M. Susana] HIV Innovat, Project Hlth MOVES, Boston, MA USA. RP Reisner, SL (reprint author), Fenway Community Hlth, Fenway Inst, 7 Haviland St, Boston, MA 02115 USA. EM sreisner@fenwayhealth.org RI Tomas, Charlene/M-9723-2014 NR 57 TC 20 Z9 22 U1 2 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD AUG PY 2009 VL 13 IS 4 BP 822 EP 831 DI 10.1007/s10461-008-9430-0 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 476WS UT WOS:000268478000022 PM 18642070 ER PT J AU Thomas, B Mimiaga, MJ Menon, S Chandrasekaran, V Murugesan, P Swaminathan, S Mayer, KH Safren, SA AF Thomas, Beena Mimiaga, Matthew J. Menon, Sunil Chandrasekaran, V. Murugesan, P. Swaminathan, Soumya Mayer, Kenneth H. Safren, Steven A. TI UNSEEN AND UNHEARD: PREDICTORS OF SEXUAL RISK BEHAVIOR AND HIV INFECTION AMONG MEN WHO HAVE SEX WITH MEN IN CHENNAI, INDIA SO AIDS EDUCATION AND PREVENTION LA English DT Article ID ALCOHOL-CONSUMPTION; UNITED-STATES; PREVENTION; PERSPECTIVE AB In India men who have sex with men (MSM) are stigmatized, understudied, and at high risk for HIV. Understanding the impact of psychosocial issues on HIV risk behavior and HIV infection can help shape culturally relevant HIV prevention interventions. Peer outreach workers recruited 210 MSM in Chennai who completed an interviewer-achninistered psychosocial assessment battery and underwent HIV testing and counseling. More than one fifth (46/210) reported unprotected anal intercourse in the past 3 months, 8% tested positive for HIV, and 26% had previously participated in an HIV prevention intervention. In a multivariable logistic-regression model controlling for age, MSM subpopulation (kothi, panthi, or double-decker), marital status, and religion, significant predictors of any unprotected anal intercourse were being less educated (adjusted odds ratio [AOR] = .54; P = .009), not having previously participated in an HIV prevention program (AOR = 3.75; p = .05), having clinically significant depression symptoms (AOR = 2.8; p = .02), and lower self-efficacy (AOR = .40; p < .0001). Significant predictors of testing positive for HIV infection were: being less educated (AOR = .53; .05) and not currently living with parent(s) (AOR = 3.71; p = .05). Given the prevalence of HIV among MSM, efforts to reach hidden subpopulations of MSM in India are still needed. Such programs for MSM in India may need to address culturally-relevant commonly co-occurring psychosocial problems to maximize chances of reducing risk for infection. C1 [Thomas, Beena; Chandrasekaran, V.; Murugesan, P.; Swaminathan, Soumya] Indian Council Med Res, TB Res Ctr, Madras, Tamil Nadu, India. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mimiaga, Matthew J.; Mayer, Kenneth H.; Safren, Steven A.] Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. RP Safren, SA (reprint author), MGH Behav Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ssafren@partners.org FU NIAID NIH HHS [P30 AI42853, P30 AI060354, P30 AI042853]; NIMH NIH HHS [R21MH085314, R21 MH085314]; PHS HHS [P30A1060354] NR 32 TC 35 Z9 35 U1 1 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD AUG PY 2009 VL 21 IS 4 BP 372 EP 383 PG 12 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 481XI UT WOS:000268845700006 PM 19670971 ER EF